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Sample records for increased crosslinker levels

  1. Resuscitation with increasing doses of diaspirin crosslinked hemoglobin in swine.

    PubMed

    Marchand, G; Dunlap, E; Farrell, L; Nigro, C; Burhop, K

    1996-09-01

    This study examined the effects of administering 0.5, 4, 10, and 30 mL/kg of Diaspirin Crosslinked Hemoglobin (DCLHb) in a swine model of non-lethal hemorrhagic shock. Thirty unanesthetized animals were bled (30 mL/kg, 1 mL/kg/min) and either recovered without treatment (Untreated Control, UC) or infused with 10 g/dL DCLHb (0.5, 4.0, 10 or 30 mL/kg at 1 mL/kg/min) or Lactated Ringer (LR, 90 mL/kg at 3 mL/kg/min). DCLHb caused dose-related increases in MAP. Both the 10 and 30 mL/kg doses of DCLHb increased MAP more than UC or LR. Lower doses of DCLHb and LR had effects on MAP similar to UC. After hemorrhage, CO increased in all groups. The effect of DCLHb on CO was dose-related. Only LR and 30 mL/kg of DCLHb transiently (through 90 min) increased CO more than UC. CO in animals given lower doses of DCLHb was comparable to UC. DCLHb (10 and 30 mL/kg) improved base excess and lactate concentrations, two indices of global perfusion, more rapidly and to a greater extent than either UC or LR. In this swine model of hemorrhage, even small doses of DCLHb exerted measurable beneficial effects on blood pressure and perfusion.

  2. Experimental scleral cross-linking increases glaucoma damage in a mouse model

    PubMed Central

    Kimball, Elizabeth C.; Nguyen, Cathy; Steinhart, Matthew R.; Nguyen, Thao D.; Pease, Mary E.; Oglesby, Ericka N.; Oveson, Brian C.; Quigley, Harry A.

    2014-01-01

    The purpose of this study was to assess the effect of a scleral cross-linking agent on susceptibility to glaucoma damage in a mouse model. CD1 mice underwent 3 subconjunctival injections of 0.5 M glyceraldehyde (GA) in 1 week, then had elevated intraocular pressure (IOP) induced by bead injection. Degree of cross-linking was measured by enzyme-linked immunosorbent assay (ELISA), scleral permeability was measured by fluorescence recovery after photobleaching (FRAP), and the mechanical effects of GA exposure were measured by inflation testing. Control mice had buffer injection or no injection in 2 separate glaucoma experiments. IOP was monitored by Tonolab and retinal ganglion cell (RGC) loss was measured by histological axon counting. To rule out undesirable effects of GA, we performed electroretinography and detailed histology of the retina. GA exposure had no detectable effects on RGC number, retinal structure or function either histologically or electrophysiologically. GA increased cross-linking of sclera by 37% in an ELISA assay, decreased scleral permeability (FRAP, p = 0.001), and produced a steeper pressure—strain behavior by in vitro inflation testing. In two experimental glaucoma experiments, GA-treated eyes had greater RGC axon loss from elevated IOP than either buffer-injected or control eyes, controlling for level of IOP exposure over time (p = 0.01, and 0.049, multivariable regression analyses). This is the first report that experimental alteration of the sclera, by cross-linking, increases susceptibility to RGC damage in mice. PMID:25285424

  3. Oxidation increases mucin polymer cross-links to stiffen airway mucus gels.

    PubMed

    Yuan, Shaopeng; Hollinger, Martin; Lachowicz-Scroggins, Marrah E; Kerr, Sheena C; Dunican, Eleanor M; Daniel, Brian M; Ghosh, Sudakshina; Erzurum, Serpel C; Willard, Belinda; Hazen, Stanley L; Huang, Xiaozhu; Carrington, Stephen D; Oscarson, Stefan; Fahy, John V

    2015-02-25

    Airway mucus in cystic fibrosis (CF) is highly elastic, but the mechanism behind this pathology is unclear. We hypothesized that the biophysical properties of CF mucus are altered because of neutrophilic oxidative stress. Using confocal imaging, rheology, and biochemical measures of inflammation and oxidation, we found that CF airway mucus gels have a molecular architecture characterized by a core of mucin covered by a web of DNA and a rheological profile characterized by high elasticity that can be normalized by chemical reduction. We also found that high levels of reactive oxygen species in CF mucus correlated positively and significantly with high concentrations of the oxidized products of cysteine (disulfide cross-links). To directly determine whether oxidation can cross-link mucins to increase mucus elasticity, we exposed induced sputum from healthy subjects to oxidizing stimuli and found a marked and thiol-dependent increase in sputum elasticity. Targeting mucin disulfide cross-links using current thiol-amino structures such as N-acetylcysteine (NAC) requires high drug concentrations to have mucolytic effects. We therefore synthesized a thiol-carbohydrate structure (methyl 6-thio-6-deoxy-α-D-galactopyranoside) and found that it had stronger reducing activity than NAC and more potent and fast-acting mucolytic activity in CF sputum. Thus, oxidation arising from airway inflammation or environmental exposure contributes to pathologic mucus gel formation in the lung, which suggests that it can be targeted by thiol-modified carbohydrates. PMID:25717100

  4. Oxidation increases mucin polymer cross-links to stiffen airway mucus gels.

    PubMed

    Yuan, Shaopeng; Hollinger, Martin; Lachowicz-Scroggins, Marrah E; Kerr, Sheena C; Dunican, Eleanor M; Daniel, Brian M; Ghosh, Sudakshina; Erzurum, Serpel C; Willard, Belinda; Hazen, Stanley L; Huang, Xiaozhu; Carrington, Stephen D; Oscarson, Stefan; Fahy, John V

    2015-02-25

    Airway mucus in cystic fibrosis (CF) is highly elastic, but the mechanism behind this pathology is unclear. We hypothesized that the biophysical properties of CF mucus are altered because of neutrophilic oxidative stress. Using confocal imaging, rheology, and biochemical measures of inflammation and oxidation, we found that CF airway mucus gels have a molecular architecture characterized by a core of mucin covered by a web of DNA and a rheological profile characterized by high elasticity that can be normalized by chemical reduction. We also found that high levels of reactive oxygen species in CF mucus correlated positively and significantly with high concentrations of the oxidized products of cysteine (disulfide cross-links). To directly determine whether oxidation can cross-link mucins to increase mucus elasticity, we exposed induced sputum from healthy subjects to oxidizing stimuli and found a marked and thiol-dependent increase in sputum elasticity. Targeting mucin disulfide cross-links using current thiol-amino structures such as N-acetylcysteine (NAC) requires high drug concentrations to have mucolytic effects. We therefore synthesized a thiol-carbohydrate structure (methyl 6-thio-6-deoxy-α-D-galactopyranoside) and found that it had stronger reducing activity than NAC and more potent and fast-acting mucolytic activity in CF sputum. Thus, oxidation arising from airway inflammation or environmental exposure contributes to pathologic mucus gel formation in the lung, which suggests that it can be targeted by thiol-modified carbohydrates.

  5. Cross-Linking in Collagen by Nonenzymatic Glycation Increases the Matrix Stiffness in Rabbit Achilles Tendon

    PubMed Central

    2004-01-01

    Nonenzymatic glycation of connective tissue matrix proteins is a major contributor to the pathology of diabetes and aging. Previously the author and colleagues have shown that nonenzymatic glycation significantly enhances the matrix stability in the Achilles tendon (Reddy et al., 2002, Arch. Biochem. Biophys., 399, 174–180). The present study was designed to gain further insight into glycation-induced collagen cross-linking and its relationship to matrix stiffness in the rabbit Achilles tendon. The glycation process was initiated by incubating the Achilles tendons (n = 6) in phosphate-buffered saline containing ribose, whereas control tendons (n = 6) were incubated in phosphate-buffered saline without ribose. Eight weeks following glycation, the biomechanical attributes as well as the degree of collagen cross-linking were determined to examine the potential associations between matrix stiffness and molecular properties of collagen. Compared to nonglycated tendons, the glycated tendons showed increased maximum load, stress, strain, Young's modulus of elasticity, and toughness indicating that glycation increases the matrix stiffness in the tendons. Glycation of tendons resulted in a considerable decrease in soluble collagen content and a significant increase in insoluble collagen and pentosidine. Analysis of potential associations between the matrix stiffness and degree of collagen cross-linking showed that both insoluble collagen and pentosidine exhibited a significant positive correlation with the maximum load, stress, and strain, Young's modulus of elasticity, and toughness (r values ranging from .61 to .94) in the Achilles tendons. However, the soluble collagen content present in neutral salt buffer, acetate buffer, and acetate buffer containing pepsin showed an inverse relation with the various biomechanical attributes tested (r values ranging from .22 to .84) in the Achilles tendons. The results of the study demonstrate that glycation-induced collagen cross-linking

  6. Enzymatic cross-linking of α-lactalbumin to produce nanoparticles with increased foam stability.

    PubMed

    Dhayal, Surender K; Delahaije, Roy J B M; de Vries, Renko J; Gruppen, Harry; Wierenga, Peter A

    2015-10-28

    Hard colloidal nanoparticles (e.g. partly hydrophobised silica), are known to make foams with very high foam-stability. Nanoparticles can also be produced from proteins by enzymatic cross-linking. Such protein based particles are more suitable for food applications, but it is not known if they provide Pickering foam stabilisation to the same extent as hard colloidal particles. α-Lactalbumin (α-LA) was cross-linked with either microbial transglutaminase (mTG) or horseradish peroxidase (HRP) to produce α-LA/mTG and α-LA/HRP nanoparticles. With both enzymes a range of nanoparticles were produced with hydrodynamic radii ranging from 20-100 nm. The adsorption of nanoparticles to the air-water interface was probed by increase in surface pressure (Π) with time. In the beginning of the Π versus time curves, there was a lag time of 10-200 s, for nanoparticles with Rh of 30-100 nm, respectively. A faster increase of Π with time was observed by increasing the ionic strength (I = 0-125 mM). The foam-ability of the nanoparticles was also found to increase with increasing ionic strength. At a fixed I, the foam-ability of the nanoparticles decreased with increasing size while their foam-stability increased. Foams produced by low-shear whipping were found to be 2 to 6 times more stable for nanoparticles than for monomeric α-LA (Rh≈ 2 nm). At an ionic strength of 125 mM ionic strength and protein concentration ≥ 10 g L(-1), the foam-stability of α-LA/mTG nanoparticles (Rh = 100 nm, ρapp = 21.6 kg m(-3)) was 2-4 times higher than α-LA/HRP nanoparticles (Rh = 90 nm, ρapp = 10.6 kg m(-3)). This indicated that foam-stablity of nanoparticles is determined not only by size but also by differences in mesoscale structure. So, indeed enzymatic cross-linking of proteins to make nanoparticles is moving a step towards particle like behavior e.g. slower adsorption and higher foam stability. However, the cross-link density should be further increased to obtain hard particle

  7. Enzymatic cross-linking of α-lactalbumin to produce nanoparticles with increased foam stability.

    PubMed

    Dhayal, Surender K; Delahaije, Roy J B M; de Vries, Renko J; Gruppen, Harry; Wierenga, Peter A

    2015-10-28

    Hard colloidal nanoparticles (e.g. partly hydrophobised silica), are known to make foams with very high foam-stability. Nanoparticles can also be produced from proteins by enzymatic cross-linking. Such protein based particles are more suitable for food applications, but it is not known if they provide Pickering foam stabilisation to the same extent as hard colloidal particles. α-Lactalbumin (α-LA) was cross-linked with either microbial transglutaminase (mTG) or horseradish peroxidase (HRP) to produce α-LA/mTG and α-LA/HRP nanoparticles. With both enzymes a range of nanoparticles were produced with hydrodynamic radii ranging from 20-100 nm. The adsorption of nanoparticles to the air-water interface was probed by increase in surface pressure (Π) with time. In the beginning of the Π versus time curves, there was a lag time of 10-200 s, for nanoparticles with Rh of 30-100 nm, respectively. A faster increase of Π with time was observed by increasing the ionic strength (I = 0-125 mM). The foam-ability of the nanoparticles was also found to increase with increasing ionic strength. At a fixed I, the foam-ability of the nanoparticles decreased with increasing size while their foam-stability increased. Foams produced by low-shear whipping were found to be 2 to 6 times more stable for nanoparticles than for monomeric α-LA (Rh≈ 2 nm). At an ionic strength of 125 mM ionic strength and protein concentration ≥ 10 g L(-1), the foam-stability of α-LA/mTG nanoparticles (Rh = 100 nm, ρapp = 21.6 kg m(-3)) was 2-4 times higher than α-LA/HRP nanoparticles (Rh = 90 nm, ρapp = 10.6 kg m(-3)). This indicated that foam-stablity of nanoparticles is determined not only by size but also by differences in mesoscale structure. So, indeed enzymatic cross-linking of proteins to make nanoparticles is moving a step towards particle like behavior e.g. slower adsorption and higher foam stability. However, the cross-link density should be further increased to obtain hard particle

  8. Increasing FCC regenerator catalyst level

    SciTech Connect

    Wong, R.F. )

    1993-11-01

    A Peruvian FCC unit's operations were improved by increasing the regenerator's catalyst level. This increase resulted in lower stack losses, an improved temperature profile, increased catalyst activity and a lower catalyst consumption rate. A more stable operation saved this Peruvian refiner over $131,000 per year in catalyst alone. These concepts and data may be suitable for your FCC unit as well.

  9. Polymers and Cross-Linking: A CORE Experiment to Help Students Think on the Submicroscopic Level

    ERIC Educational Resources Information Center

    Bruce, Mitchell R. M.; Bruce, Alice E.; Avargil, Shirly; Amar, Francois G.; Wemyss, Thomas M.; Flood, Virginia J.

    2016-01-01

    The Polymers and Cross-Linking experiment is presented via a new three phase learning cycle: CORE (Chemical Observations, Representations, Experimentation), which is designed to model productive chemical inquiry and to promote a deeper understanding about the chemistry operating at the submicroscopic level. The experiment is built on two familiar…

  10. Collagen Cross-Linking Using Rose Bengal and Green Light to Increase Corneal Stiffness

    PubMed Central

    Cherfan, Daniel; Verter, E. Eri; Melki, Samir; Gisel, Thomas E.; Doyle, Francis J.; Scarcelli, Giuliano; Yun, Seok Hyun; Redmond, Robert W.; Kochevar, Irene E.

    2013-01-01

    Purpose. Photochemical cross-linking of corneal collagen is an evolving treatment for keratoconus and other ectatic disorders. We evaluated collagen cross-linking by rose bengal plus green light (RGX) in rabbit eyes and investigated factors important for clinical application. Methods. Rose bengal (RB, 0.1%) was applied to deepithelialized corneas of enucleated rabbit eyes for 2 minutes. The diffusion distance of RB into the stroma was measured by fluorescence microscopy on frozen sections. RB-stained corneas were exposed to green (532-nm) light for 3.3 to 9.9 minutes (50–150 J/cm2). Changes in the absorption spectrum during the irradiation were recorded. Corneal stiffness was measured by uniaxial tensiometry. The spatial distribution of the stromal elastic modulus was assessed by Brillouin microscopy. Viable keratocytes were counted on H&E-stained sections 24 hours posttreatment. Results. RB penetrated approximately 100 μm into the corneal stroma and absorbed >90% of the incident green light. RGX (150 J/cm2) increased stromal stiffness by 3.8-fold. The elastic modulus increased in the anterior approximately 120 μm of stroma. RB was partially photobleached during the 2-minute irradiation, but reapplication of RB blocked light transmission by >70%. Spectral measurements suggested that RGX initiated cross-linking by an oxygen-dependent mechanism. RGX did not decrease keratocyte viability. Conclusions. RGX significantly increases cornea stiffness in a rapid treatment (≅12 minutes total time), does not cause toxicity to keratocytes and may be used to stiffen corneas thinner than 400 μm. Thus, RGX may provide an attractive approach to inhibit progression of keratoconus and other ectatic disorders. PMID:23599326

  11. Understanding of the Viscoelastic Response of the Human Corneal Stroma Induced by Riboflavin/UV-A Cross-Linking at the Nano Level

    PubMed Central

    Labate, Cristina; De Santo, Maria Penelope; Lombardo, Giuseppe; Lombardo, Marco

    2015-01-01

    Purpose To investigate the viscoelastic changes of the human cornea induced by riboflavin/UV-A cross-linking using Atomic Force Microscopy (AFM) at the nano level. Methods Seven eye bank donor corneas were investigated, after gently removing the epithelium, using a commercial AFM in the force spectroscopy mode. Silicon cantilevers with tip radius of 10 nm and spring elastic constants between 26- and 86-N/m were used to probe the viscoelastic properties of the anterior stroma up to 3 µm indentation depth. Five specimens were tested before and after riboflavin/UV-A cross-linking; the other two specimens were chemically cross-linked using glutaraldehyde 2.5% solution and used as controls. The Young’s modulus (E) and the hysteresis (H) of the corneal stroma were quantified as a function of the application load and scan rate. Results The Young’s modulus increased by a mean of 1.1-1.5 times after riboflavin/UV-A cross-linking (P<0.05). A higher increase of E, by a mean of 1.5-2.6 times, was found in chemically cross-linked specimens using glutaraldehyde 2.5% (P<0.05). The hysteresis decreased, by a mean of 0.9-1.5 times, in all specimens after riboflavin/UV-A cross-linking (P<0.05). A substantial decrease of H, ranging between 2.6 and 3.5 times with respect to baseline values, was observed in glutaraldehyde-treated corneas (P<0.05). Conclusions The present study provides the first evidence that riboflavin/UV-A cross-linking induces changes of the viscoelastic properties of the cornea at the scale of stromal molecular interactions. PMID:25830534

  12. Water dispersible cross-linked magnetic chitosan beads for increasing the antimicrobial efficiency of aminoglycoside antibiotics.

    PubMed

    Grumezescu, Alexandru Mihai; Andronescu, Ecaterina; Holban, Alina Maria; Ficai, Anton; Ficai, Denisa; Voicu, Georgeta; Grumezescu, Valentina; Balaure, Paul Cătălin; Chifiriuc, Carmen Mariana

    2013-09-15

    The aim of this study was to obtain a nano-active system to improve antibiotic activity of certain drugs by controlling their release. Magnetic composite nanomaterials based on magnetite core and cross-linked chitosan shell were synthesized via the co-precipitation method and characterized by Fourier transform infrared spectroscopy (FT-IR), infrared microscopy (IRM), scanning electron microscopy (SEM), dynamic light scattering (DLS), thermogravimetric analysis (TGA) and X-ray diffraction (XRD). The prepared magnetic composite nanomaterials exhibit a significant potentiating effect on the activity of two cationic (kanamycin and neomycin) drugs, reducing the amount of antibiotics necessary for the antimicrobial effect. The increase in the antimicrobial activity was explained by the fact that the obtained nanosystems provide higher surface area to volume ratio, resulting into higher surface charge density thus increasing affinity to microbial cell and also by controlling their release. In addition to the nano-effect, the positive zeta potential of the synthesized magnetite/cross-linked chitosan core/shell magnetic nanoparticles allows for a more favorable interaction with the usually negatively charged cell wall of bacteria. The novelty of the present contribution is just the revealing of this synergistic effect exhibited by the synthesized water dispersible magnetic nanocomposites on the activity of different antibiotics against Gram-positive and Gram-negative bacterial strains. The results obtained in this study recommend these magnetic water dispersible nanocomposite materials for applications in the prevention and treatment of infectious diseases. PMID:23830944

  13. Water dispersible cross-linked magnetic chitosan beads for increasing the antimicrobial efficiency of aminoglycoside antibiotics.

    PubMed

    Grumezescu, Alexandru Mihai; Andronescu, Ecaterina; Holban, Alina Maria; Ficai, Anton; Ficai, Denisa; Voicu, Georgeta; Grumezescu, Valentina; Balaure, Paul Cătălin; Chifiriuc, Carmen Mariana

    2013-09-15

    The aim of this study was to obtain a nano-active system to improve antibiotic activity of certain drugs by controlling their release. Magnetic composite nanomaterials based on magnetite core and cross-linked chitosan shell were synthesized via the co-precipitation method and characterized by Fourier transform infrared spectroscopy (FT-IR), infrared microscopy (IRM), scanning electron microscopy (SEM), dynamic light scattering (DLS), thermogravimetric analysis (TGA) and X-ray diffraction (XRD). The prepared magnetic composite nanomaterials exhibit a significant potentiating effect on the activity of two cationic (kanamycin and neomycin) drugs, reducing the amount of antibiotics necessary for the antimicrobial effect. The increase in the antimicrobial activity was explained by the fact that the obtained nanosystems provide higher surface area to volume ratio, resulting into higher surface charge density thus increasing affinity to microbial cell and also by controlling their release. In addition to the nano-effect, the positive zeta potential of the synthesized magnetite/cross-linked chitosan core/shell magnetic nanoparticles allows for a more favorable interaction with the usually negatively charged cell wall of bacteria. The novelty of the present contribution is just the revealing of this synergistic effect exhibited by the synthesized water dispersible magnetic nanocomposites on the activity of different antibiotics against Gram-positive and Gram-negative bacterial strains. The results obtained in this study recommend these magnetic water dispersible nanocomposite materials for applications in the prevention and treatment of infectious diseases.

  14. Molecular-level modeling of the viscoelasticity of crosslinked polymers: Effect of time and temperature

    SciTech Connect

    Simon, P.P.; Ploehn, H.J.

    1997-05-01

    We present a new molecular-level picture of chain dynamics for describing the viscoelasticity of crosslinked polymers. The associated mathematical model consists of a time-dependent momentum balance on a representative polymer segment in the crosslinked network, plus phenomenological expressions for forces acting on the segments. These include a cohesive force that accounts for intermolecular attraction, an entropic force describing the thermodynamics governing chain conformations, and a frictional force that captures the temperature dependence of relative chain motion. We treat the case of oscillatory uniaxial deformation. Solution of the model equations in the frequency domain yields the dynamic moduli as functions of temperature and frequency. The model reproduces all of the qualitative features of experimental dynamic modulus data across the complete spectrum of time and temperature, spanning the glassy zone, the {beta} transition, the dynamic glass transition, and the rubbery zone. All of the model parameters can be evaluated through the use of independent experimental data. Comparison of model predictions with experimental data yields good quantitative agreement outside of the glass transition region. {copyright} {ital 1997 Society of Rheology.}

  15. Laser welding and collagen crosslinks

    SciTech Connect

    Reiser, K.M.; Last, J.A.; Small, W. IV; Maitland, D.J.; Heredia, N.J.; Da Silva, L.B.; Matthews, D.L.

    1997-02-20

    Strength and stability of laser-welded tissue may be influenced, in part, by effects of laser exposure on collagen crosslinking. We therefore studied effects of diode laser exposure (805 nm, 1-8 watts, 30 seconds) + indocyanine green dye (ICG) on calf tail tendon collagen crosslinks. Effect of ICG dye alone on crosslink content prior to laser exposure was investigated; unexpectedly, we found that ICG-treated tissue had significantly increased DHLNL and OHP, but not HLNL. Laser exposure after ICG application reduced elevated DHLNL and OHP crosslink content down to their native levels. The monohydroxylated crosslink HLNL was inversely correlated with laser output (p<0.01 by linear regression analysis). DHLNL content was highly correlated with content of its maturational product, OHP, suggesting that precursor-product relations are maintained. We conclude that: (1)ICG alone induces DHLNL and OHP crosslink formation; (2)subsequent laser exposure reduces the ICG-induced crosslinks down to native levels; (3)excessive diode laser exposure destroys normally occurring HLNL crosslinks.

  16. Increasing the Depth of Mass-Spectrometry-Based Structural Analysis of Protein Complexes through the Use of Multiple Cross-Linkers.

    PubMed

    Ding, Yue-He; Fan, Sheng-Bo; Li, Shuang; Feng, Bo-Ya; Gao, Ning; Ye, Keqiong; He, Si-Min; Dong, Meng-Qiu

    2016-04-19

    Chemical cross-linking of proteins coupled with mass spectrometry (CXMS) is a powerful tool to study protein folding and to map the interfaces between interacting proteins. The most commonly used cross-linkers in CXMS are BS(3) and DSS, which have similar structures and generate the same linkages between pairs of lysine residues in spatial proximity. However, there are cases where no cross-linkable lysine pairs are present at certain regions of a protein or at the interface of two interacting proteins. In order to find the cross-linkers that can best complement the performance of BS(3) and DSS, we tested seven additional cross-linkers that either have different spacer arm structures or that target different amino acids (BS(2)G, EGS, AMAS, GMBS, Sulfo-GMBS, EDC, and TFCS). Using BSA, aldolase, the yeast H/ACA protein complex, and E. coli 70S ribosomes, we showed that, in terms of providing structural information not obtained through the use of BS(3) and DSS, EGS and Sulfo-GMBS worked better than the other cross-linkers that we tested. EGS generated a large number of cross-links not seen with the other amine-specific cross-linkers, possibly due to its hydrophilic spacer arm. We demonstrate that incorporating the cross-links contributed by the EGS and amine-sulfhydryl cross-linkers greatly increased the accuracy of Rosetta in docking the structure of the yeast H/ACA protein complex. Given the improved depth of useful information it can provide, we suggest that the multilinker CXMS approach should be used routinely when the amount of a sample permits. PMID:27010980

  17. Imidate-Based Cross-Linkers for Structural Proteomics: Increased Charge of Protein and Peptide Ions and CID and ECD Fragmentation Studies

    NASA Astrophysics Data System (ADS)

    Koolen, Hector H. F.; Gomes, Alexandre F.; Schwab, Nicolas V.; Eberlin, Marcos N.; Gozzo, Fabio C.

    2014-07-01

    Chemical cross-linking is an attractive low-resolution technique for structural studies of protein complexes. Distance constraints obtained from cross-linked peptides identified by mass spectrometry (MS) are used to construct and validate protein models. Amidinating cross-linkers such as diethyl suberthioimidate (DEST) have been used successfully in chemical cross-linking experiments. In this work, the application of a commercial diimidate cross-linking reagent, dimethyl suberimidate (DMS), was evaluated with model peptides and proteins. The peptides were designed with acetylated N-termini followed by random sequences containing two Lys residues separated by an Arg residue. After cross-linking reactions, intra- and intermolecular cross-linked species were submitted to CID and ECD dissociations to study their fragmentation features in the gas phase. Fragmentation of intramolecular peptides by collision induced dissociation (CID) demonstrates a unique two-step fragmentation pathway involving formation of a ketimine as intermediate. Electron capture and electron transfer dissociation (ECD and ETD) experiments demonstrated that the cyclic moiety is not dissociated. Intermolecular species demonstrated previously described fragmentation behavior in both CID and ECD experiments. The charge state distributions (CSD) obtained after reaction with DMS were compared with those obtained with disuccinimidyl suberate (DSS). CSDs for peptides and proteins were increased after their reaction with DMS, owing to the higher basicity of DMS modified species. These features were also observed in LC-MS experiments with bovine carbonic anhydrase II (BCA) after cross-linking with DMS and tryptic proteolysis. Cross-linked peptides derived from this protein were identified at high confidence and those species were in agreement with the crystal structure of BCA.

  18. Elevated levels of DNA-protein crosslinks and micronuclei in peripheral lymphocytes of tannery workers exposed to trivalent chromium.

    PubMed

    Medeiros, M G; Rodrigues, A S; Batoréu, M C; Laires, A; Rueff, J; Zhitkovich, A

    2003-01-01

    DNA-protein crosslinks (DPC) are a promising biomarker of exposure to hexavalent chromium, a known human carcinogen. Although trivalent chromium is considered to have much lower toxicity, the risk involved in chronic exposure is uncertain. DPC may be a useful tool in clarifying this risk, by signaling an exposure of body tissues to biologically active forms of chromium. DPC quantification was carried out in lymphocytes of a group of tannery workers exposed to trivalent chromium, a small group of manual metal arc stainless steel welders exposed to hexavalent chromium and a control group. This biomarker was compared with the frequency of micronuclei in cytokinesis blocked peripheral lymphocytes as a biomarker of cytogenetic lesions and total plasma and urine chromium levels as an index of exposure. The results indicate a significant increase in the formation of DPC in tannery workers compared with controls (0.88 +/- 0.19 versus 0.57 +/- 0.21%, P < 0.001, Mann-Whitney test) and an even higher level of DPC in welders (2.22 +/- 1.12%, P = 0.03). Tanners showed a significant increase in micronucleated cells compared with controls (6.35 +/- 2.94 versus 3.58 +/- 1.69 per thousand, P < 0.01), whereas in welders this increase was not significant (5.40 +/- 1.67 per thousand ). Urinary chromium was increased in both groups, with a greater increase observed in tanners compared with controls (2.63 +/- 1.62 versus 0.70 +/- 0.38 microg/g creatinine, P < 0.001) than in welders (1.90 +/- 0.37 microg/g creatinine, P < 0.005). Plasma chromium was also increased in both groups (tanners 2.43 +/- 2.11 microg/l, P < 0.001, welders 1.55 +/- 0.67 microg/l, P < 0.005 versus controls 0.41 +/- 0.11 microg/l). In summary, chronic occupational exposure to trivalent chromium can lead to a detectable increase in lymphocyte DNA damage which correlates with a significant exposure of the cells to the metal.

  19. The process of EDC-NHS Cross-linking of reconstituted collagen fibres increases collagen fibrillar order and alignment

    PubMed Central

    Shepherd, D.V.; Shepherd, J.H.; Ghose, S.; Kew, S.J.; Cameron, R.E.; Best, S.M.

    2014-01-01

    We describe the production of collagen fibre bundles through a multi-strand, semi-continuous extrusion process. Cross-linking using an EDC (1-ethyl-3-(3-dimethylaminopropyl)carbodiimide), NHS (N-hydroxysuccinimide) combination was considered. Atomic Force Microscopy (AFM) and Raman spectroscopy focused on how cross-linking affected the collagen fibrillar structure. In the cross-linked fibres, a clear fibrillar structure comparable to native collagen was observed which was not observed in the non-cross-linked fibre. The amide III doublet in the Raman spectra provided additional evidence of alignment in the cross-linked fibres. Raman spectroscopy also indicated no residual polyethylene glycol (from the fibre forming buffer) or water in any of the fibres. PMID:25506518

  20. The process of EDC-NHS cross-linking of reconstituted collagen fibres increases collagen fibrillar order and alignment

    SciTech Connect

    Shepherd, D. V. Shepherd, J. H.; Cameron, R. E.; Best, S. M.; Ghose, S.; Kew, S. J.

    2015-01-01

    We describe the production of collagen fibre bundles through a multi-strand, semi-continuous extrusion process. Cross-linking using an EDC (1-ethyl-3-(3-dimethylaminopropyl)carbodiimide), NHS (N-hydroxysuccinimide) combination was considered. Atomic Force Microscopy and Raman spectroscopy focused on how cross-linking affected the collagen fibrillar structure. In the cross-linked fibres, a clear fibrillar structure comparable to native collagen was observed which was not observed in the non-cross-linked fibre. The amide III doublet in the Raman spectra provided additional evidence of alignment in the cross-linked fibres. Raman spectroscopy also indicated no residual polyethylene glycol (from the fibre forming buffer) or water in any of the fibres.

  1. Pathogen Inactivating Properties and Increased Sensitivity in Molecular Diagnostics by PAXgene, a Novel Non-Crosslinking Tissue Fixative

    PubMed Central

    Loibner, Martina; Buzina, Walter; Viertler, Christian; Groelz, Daniel; Hausleitner, Anja; Siaulyte, Gintare; Kufferath, Iris; Kölli, Bettina; Zatloukal, Kurt

    2016-01-01

    Background Requirements on tissue fixatives are getting more demanding as molecular analysis becomes increasingly relevant for routine diagnostics. Buffered formaldehyde in pathology laboratories for tissue fixation is known to cause chemical modifications of biomolecules which affect molecular testing. A novel non-crosslinking tissue preservation technology, PAXgene Tissue (PAXgene), was developed to preserve the integrity of nucleic acids in a comparable way to cryopreservation and also to preserve morphological features comparable to those of formalin fixed samples. Methods Because of the excellent preservation of biomolecules by PAXgene we investigated its pathogen inactivation ability and biosafety in comparison to formalin by in-vitro testing of bacteria, human relevant fungi and human cytomegalovirus (CMV). Guidelines for testing disinfectants served as reference for inactivation assays. Furthermore, we tested the properties of PAXgene for detection of pathogens by PCR based assays. Results All microorganisms tested were similarly inactivated by PAXgene and formalin except Clostridium sporogenes, which remained viable in seven out of ten assays after PAXgene treatment and in three out of ten assays after formalin fixation. The findings suggest that similar biosafety measures can be applied for PAXgene and formalin fixed samples. Detection of pathogens in PCR-based diagnostics using two CMV assays resulted in a reduction of four to ten quantification cycles of PAXgene treated samples which is a remarkable increase of sensitivity. Conclusion PAXgene fixation might be superior to formalin fixation when molecular diagnostics and highly sensitive detection of pathogens is required in parallel to morphology assessment. PMID:26974150

  2. Exosomes from hypoxic endothelial cells have increased collagen crosslinking activity through up-regulation of lysyl oxidase-like 2.

    PubMed

    de Jong, Olivier G; van Balkom, Bas W M; Gremmels, Hendrik; Verhaar, Marianne C

    2016-02-01

    Exosomes are important mediators of intercellular communication. Additionally, they contain a variety of components capable of interacting with the extracellular matrix (ECM), including integrins, matrix metalloproteinases and members of the immunoglobin superfamily. Despite these observations, research on exosome-ECM interactions is limited. Here, we investigate whether the exosome-associated lysyl oxidase family member lysyl oxidase-like 2 (LOXL2) is involved in ECM remodelling. We found that LOXL2 is present on the exterior of endothelial cell (EC)-derived exosomes, placing it in direct vicinity of the ECM. It is up-regulated twofold in EC-derived exosomes cultured under hypoxic conditions. Intact exosomes from hypoxic EC and LOXL2 overexpressing EC show increased activity in a fluorometric lysyl oxidase enzymatic activity assay as well as in a collagen gel contraction assay. Concordantly, knockdown of LOXL2 in exosome-producing EC in both normal and hypoxic conditions reduces activity of exosomes in both assays. Our findings show for the first time that ECM crosslinking by EC-derived exosomes is mediated by LOXL2 under the regulation of hypoxia, and implicate a role for exosomes in hypoxia-regulated focal ECM remodelling, a key process in both fibrosis and wound healing.

  3. Cross-Linking Aromatic Polymers With Ionizing Radiation

    NASA Technical Reports Server (NTRS)

    Bell, Vernon L.; Havens, Stephen J.

    1987-01-01

    Resistance to heat and solvents increased. Certain aromatic polymers containing radiation-sensitive methylene groups cross-linked through methylene groups upon exposure to ionizing radiation. Cross-linked polymers resistant to most organic solvents and generally more resistant to high temperatures, with less tendency to creep under load. No significant embrittlement of parts fabricated from these polymers when degree of cross-linking, as controlled by irradiation dose, kept at moderate level.

  4. Crosslinked Polyamide

    DOEpatents

    Huang, Zhi H.; McDonald, William F.; Wright, Stacy C.; Taylor, Andrew C.

    2002-06-04

    A crosslinked polyamide material and a process for preparing the crosslinked polyamide material are disclosed. The crosslinked polyamide material comprises a crosslinked chemical combination of (1) a polyamide of the formula: ##STR1## wherein n is between about 50 and 10,000, wherein each R is between 1 and 50 carbon atoms alone and is optionally substituted with heteroatoms, oxygen, nitrogen, sulfur, or phosphorus and combinations thereof, wherein multiple of the R are in vertically aligned spaced relationship along a backbone forming the polyamide, and wherein two or more of the R contain an amino group; and (2) a crosslinking agent containing at least two functional groups capable of reacting with the amino groups of the polyamide. In one embodiment of the invention, the crosslinking agent is an aliphatic or aromatic isocyanate compound having 2 or more --N.dbd.C.dbd.O groups. In another embodiment of the invention, the crosslinking agent is an aliphatic aldehyde or aromatic aldehyde compound having 2 or more --CHO groups. In still another embodiment of the invention, the crosslinking agent is selected from a phosphine having the general formula (A).sub.2 P(B) and mixtures thereof, wherein A is hydroxyalkyl, and B is hydroxyalkyl, alkyl, or aryl. In yet another embodiment of the invention, the crosslinking agent is selected from the group consisting of epoxy resins having more than one epoxide group per molecule.

  5. Unified wear model for highly crosslinked ultra-high molecular weight polyethylenes (UHMWPE).

    PubMed

    Muratoglu, O K; Bragdon, C R; O'Connor, D O; Jasty, M; Harris, W H; Gul, R; McGarry, F

    1999-08-01

    Crosslinking has been shown to improve the wear resistance of ultra-high molecular weight polyethylene in both in vitro and clinical in vivo studies. The molecular mechanisms and material properties that are responsible for this marked improvement in wear resistance are still not well understood. In fact, following crosslinking a number of mechanical properties of UHMWPE are decreased including toughness, modulus, ultimate tensile strength, yield strength, and hardness. In general, these changes would be expected to constitute a precursor for lower wear resistance, presenting a paradox in that wear resistance increases with crosslinking. In order to understand better and to analyze this paradoxical behaviour of crosslinked UHMWPE, we investigated the wear behavior of (i) radiation-crosslinked GUR 1050 resin, (ii) peroxide-crosslinked GUR 1050 resin and (iii) peroxide-crosslinked Himont 1900 resin using a bi-directional pin-on-disk (POD) machine. Wear behavior was analyzed as a function of crystallinity, ultimate tensile strength (UTS), yield strength (YS), and molecular weight between crosslinks (Mc). The crosslink density increased with increasing radiation dose level and initial peroxide content. The UTS, YS, and crystallinity decreased with increasing crosslink density. While these variations followed the same trend, the absolute changes as a function of crosslink density were different for the three types of crosslinked UHMWPE studied. There was no unified correlation for the wear behavior of the three types of crosslinked UHMWPE with the crystallinity, UTS and YS. However, the POD wear rate showed the identical linear dependence on Mc with all three types of crosslinked UHMWPEs studied. Therefore, we have strong evidence to propose that Mc or crosslink density is a fundamental material property that governs the lubricated adhesive and abrasive wear mechanisms of crosslinked UHMWPEs, overriding the possible effects of other material properties such as UTS, YS

  6. Urinary levels of cross-linked N-terminal telopeptide of type I collagen and nutritional status in Japanese professional baseball players.

    PubMed

    Iwamoto, Jun; Takeda, Tsuyoshi; Uenishi, Kazuhiro; Ishida, Hiromi; Sato, Yoshihiro; Matsumoto, Hideo

    2010-09-01

    The objective of the present study was to investigate the nutritional status from the aspect of bone metabolism in Japanese elite male athletes with increased bone resorption. Urinary levels of a bone resorption marker, cross-linked N-terminal telopeptide of type 1 collagen (NTX), were measured in 71 professional baseball players (age, 18-39 years); the mean urinary NTX level was 65.6 (range, 17.5-269.0) nM BCE/mM Cr. Of 71 athletes, 9 with high levels of urinary NTX (greater than mean + 1 SD) were examined by measuring serum biochemical markers and nutritional assessment (simple food frequency questionnaire). Serum biochemical marker analysis showed that 7 of these 9 athletes had vitamin D insufficiency, as indicated by low serum levels of 25-hydroxyvitamin D, and that all 9 athletes showed vitamin K insufficiency as indicated by low levels of vitamins K(1) and K(2). Nutritional assessment revealed high intakes of protein and low intakes of calcium and vitamin D based on adequate intake (AI). However, daily vitamin K intake achieved the AI. These results suggest that there exist elite male athletes who show increased bone resorption and calcium and vitamin D insufficiency. However, there was a discrepancy between vitamin K intake and serum levels of vitamins K(1) and K(2). The present study raised an issue regarding the nutritional status from the point of view of bone metabolism in elite male athletes such as professional baseball players.

  7. Oxidation resistant peroxide cross-linked UHMWPE produced by blending and surface diffusion

    NASA Astrophysics Data System (ADS)

    Gul, Rizwan M.; Oral, Ebru; Muratoglu, Orhun K.

    2014-06-01

    Ultra-high molecular weight polyethylene (UHMWPE) has been widely used as acetabular cup in total hip replacement (THR) and tibial component in total knee replacement (TKR). Crosslinking of UHMWPE has been successful used to improve its wear performance leading to longer life of orthopedic implants. Crosslinking can be performed by radiation or organic peroxides. Peroxide crosslinking is a convenient process as it does not require specialized equipment and the level of crosslinking can be manipulated by changing the amount of peroxide added. However, there is concern about the long-term stability of these materials due to possible presence of by-products. Vitamin E has been successfully used to promote long-term oxidative stability of UHMWPE. In this study, UHMWPE has been crosslinked using organic peroxide in the presence of Vitamin E to produce an oxidation resistant peroxide crosslinked material. Crosslinking was performed both in bulk by mixing peroxide and resin, and only on the surface using diffusion of peroxides.The results show that UHMWPE can be crosslinked using organic peroxides in the presence of vitamin E by both methods. However, the level of crosslinking decreases with the increase in vitamin E content. The wear resistance increases with the increase in crosslink density, and oxidation resistance significantly increases due to the presence of vitamin E.

  8. Crosslinking biopolymers for biomedical applications.

    PubMed

    Reddy, Narendra; Reddy, Roopa; Jiang, Qiuran

    2015-06-01

    Biomaterials made from proteins, polysaccharides, and synthetic biopolymers are preferred but lack the mechanical properties and stability in aqueous environments necessary for medical applications. Crosslinking improves the properties of the biomaterials, but most crosslinkers either cause undesirable changes to the functionality of the biopolymers or result in cytotoxicity. Glutaraldehyde, the most widely used crosslinking agent, is difficult to handle and contradictory views have been presented on the cytotoxicity of glutaraldehyde-crosslinked materials. Recently, poly(carboxylic acids) that can crosslink in both dry and wet conditions have been shown to provide the desired improvements in tensile properties, increase in stability under aqueous conditions, and also promote cell attachment and proliferation. Green chemicals and newer crosslinking approaches are necessary to obtain biopolymeric materials with properties desired for medical applications.

  9. Influence of Cross-Linker Concentration on the Functionality of Carbodiimide Cross-Linked Gelatin Membranes for Retinal Sheet Carriers.

    PubMed

    Lai, Jui-Yang; Li, Ya-Ting

    2011-01-01

    Carbodiimide cross-linking can easily regulate the functionality of gelatin carriers used for retinal sheet delivery. This paper investigates the effect of cross-linker concentrations (0-0.4 mmol EDC/mg gelatin membrane (GM)) on the properties of the chemically-modified GMs. ATR-FT-IR and ninhydrin analyses results consistently indicated that the EDC cross-linking reaction approaches saturation at concentrations around 0.02 mmol EDC/mg GM. The thermal stability and resistance to water dissolution and collagenase digestion were significantly enhanced with increasing cross-linker concentration from 0.001 to 0.02 mmol EDC/mg GM. In addition, the chemical cross-linking did not affect the ability to form a tissue-encapsulating structure at 37°C. Irrespective of their cross-linking degree, the GMs had an appropriate degradation rate sufficient to allow tissue integration. It was noted that, although high cross-linker concentrations can be used to improve the delivery efficiency of gelatin samples, the treatment with 0.1-0.4 mmol EDC/mg GM may lead to poor biocompatibility. Results of Live/Dead and pro-inflammatory cytokine expression analyses showed that the exposure of ARPE-19 cultures to the test materials cross-linked with a concentration ≥0.1 mmol EDC/mg GM induces significant cytotoxicity and high levels of interleukin-1β and interleukin-6. However, the presence of EDC cross-linked gelatin membranes in the culture medium had no effect on the glutamate uptake capacity. It is concluded that among the cross-linked gelatin samples studied, 0.02 mmol EDC/mg GM is the best cross-linker concentration for preparation of retinal sheet delivery carriers.

  10. Building a better infarct: Modulation of collagen cross-linking to increase infarct stiffness and reduce left ventricular dilation post-myocardial infarction.

    PubMed

    Voorhees, Andrew P; DeLeon-Pennell, Kristine Y; Ma, Yonggang; Halade, Ganesh V; Yabluchanskiy, Andriy; Iyer, Rugmani Padmanabhan; Flynn, Elizabeth; Cates, Courtney A; Lindsey, Merry L; Han, Hai-Chao

    2015-08-01

    Matrix metalloproteinase-9 (MMP-9) deletion attenuates collagen accumulation and dilation of the left ventricle (LV) post-myocardial infarction (MI); however the biomechanical mechanisms underlying the improved outcome are poorly understood. The aim of this study was to determine the mechanisms whereby MMP-9 deletion alters collagen network composition and assembly in the LV post-MI to modulate the mechanical properties of myocardial scar tissue. Adult C57BL/6J wild-type (WT; n=88) and MMP-9 null (MMP-9(-/-); n=92) mice of both sexes underwent permanent coronary artery ligation and were compared to day 0 controls (n=42). At day 7 post-MI, WT LVs displayed a 3-fold increase in end-diastolic volume, while MMP-9(-/-) showed only a 2-fold increase (p<0.05). Biaxial mechanical testing revealed that MMP-9(-/-) infarcts were stiffer than WT infarcts, as indicated by a 1.3-fold reduction in predicted in vivo circumferential stretch (p<0.05). Paradoxically, MMP-9(-/-) infarcts had a 1.8-fold reduction in collagen deposition (p<0.05). This apparent contradiction was explained by a 3.1-fold increase in lysyl oxidase (p<0.05) in MMP-9(-/-) infarcts, indicating that MMP-9 deletion increased collagen cross-linking activity. Furthermore, MMP-9 deletion led to a 3.0-fold increase in bone morphogenetic protein-1, the metalloproteinase that cleaves pro-collagen and pro-lysyl oxidase (p<0.05) and reduced fibronectin fragmentation by 49% (p<0.05) to enhance lysyl oxidase activity. We conclude that MMP-9 deletion increases infarct stiffness and prevents LV dilation by reducing collagen degradation and facilitating collagen assembly and cross-linking through preservation of the fibronectin network and activation of lysyl oxidase.

  11. Crosslinking of agarose bioplastic using citric acid.

    PubMed

    Awadhiya, Ankur; Kumar, David; Verma, Vivek

    2016-10-20

    We report chemical crosslinking of agarose bioplastic using citric acid. Crosslinking was confirmed using Fourier transform infrared (FTIR) spectroscopy. The effects of crosslinking on the tensile strength, swelling, thermal stability, and degradability of the bioplastic were studied in detail. The tensile strength of the bioplastic films increased from 25.1MPa for control films up to a maximum of 52.7MPa for citric acid crosslinked films. At 37°C, the amount of water absorbed by crosslinked agarose bioplastic was only 11.5% of the amount absorbed by non-crosslinked controls. Thermogravimetric results showed that the crosslinked samples retain greater mass at high temperature (>450°C) than control samples. Moreover, while the crosslinked films were completely degradable, the rate of degradation was lower compared to non-crosslinked controls.

  12. Crosslinking of agarose bioplastic using citric acid.

    PubMed

    Awadhiya, Ankur; Kumar, David; Verma, Vivek

    2016-10-20

    We report chemical crosslinking of agarose bioplastic using citric acid. Crosslinking was confirmed using Fourier transform infrared (FTIR) spectroscopy. The effects of crosslinking on the tensile strength, swelling, thermal stability, and degradability of the bioplastic were studied in detail. The tensile strength of the bioplastic films increased from 25.1MPa for control films up to a maximum of 52.7MPa for citric acid crosslinked films. At 37°C, the amount of water absorbed by crosslinked agarose bioplastic was only 11.5% of the amount absorbed by non-crosslinked controls. Thermogravimetric results showed that the crosslinked samples retain greater mass at high temperature (>450°C) than control samples. Moreover, while the crosslinked films were completely degradable, the rate of degradation was lower compared to non-crosslinked controls. PMID:27474543

  13. Plasma FGF23 levels increase rapidly after acute kidney injury

    PubMed Central

    Christov, Marta; Waikar, Sushrut; Pereira, Renata; Havasi, Andrea; Leaf, David E.; Goltzman, David; Pajevic, Paola Divieti; Wolf, Myles; Jüppner, Harald

    2013-01-01

    Emerging evidence suggests that fibroblast growth factor 23 (FGF23) levels are elevated in patients with acute kidney injury (AKI). In order to determine how early this increase occurs we used a murine folic acid nephropathy model and found that plasma FGF23 levels increased significantly from baseline already after 1 hour of AKI, with an 18-fold increase at 24 hours. Similar elevations of FGF23 levels were found when AKI was induced in mice with osteocyte-specific parathyroid hormone receptor ablation or the global deletion of parathyroid hormone or vitamin D receptor, indicating that the increase in FGF23 was independent of parathyroid hormone and vitamin D signaling. Furthermore, FGF23 levels increased to a similar extent in wild-type mice maintained on normal or phosphate-depleted diets prior to induction of AKI, indicating that the marked FGF23 elevation is at least partially independent of dietary phosphate. Bone production of FGF23 was significantly increased in AKI. The half-life of intravenously administered recombinant FGF23 was only modestly increased. Consistent with the mouse data, plasma FGF23 levels rose 15.9-fold by 24 hours following cardiac surgery in patients who developed AKI. The levels were significantly higher than in those without postoperative AKI. Thus, circulating FGF23 levels rise rapidly during AKI in rodents and humans. In mice this increase is independent of established modulators of FGF23 secretion. PMID:23657144

  14. Constitutive Modeling of Crosslinked Nanotube Materials

    NASA Technical Reports Server (NTRS)

    Odegard, G. M.; Frankland, S. J. V.; Herzog, M. N.; Gates, T. S.; Fay, C. C.

    2004-01-01

    A non-linear, continuum-based constitutive model is developed for carbon nanotube materials in which bundles of aligned carbon nanotubes have varying amounts of crosslinks between the nanotubes. The model accounts for the non-linear elastic constitutive behavior of the material in terms of strain, and is developed using a thermodynamic energy approach. The model is used to examine the effect of the crosslinking on the overall mechanical properties of variations of the crosslinked carbon nanotube material with varying degrees of crosslinking. It is shown that the presence of the crosslinks has significant effects on the mechanical properties of the carbon nanotube materials. An increase in the transverse shear properties is observed when the nanotubes are crosslinked. However, this increase is accompanied by a decrease in axial mechanical properties of the nanotube material upon crosslinking.

  15. Cocaine selectively increases striatonigral dynorphin levels by a dopaminergic mechanism.

    PubMed

    Sivam, S P

    1989-09-01

    The influence of the acute (single dose) or subchronic (one dose daily for 4 days) administration of cocaine to Sprague-Dawley rats on striatal enkephalin (Met5-enkephalin) and striatonigral tachykinin (substance P) and dynorphin [dynorphin A (1-8), DYN] levels was investigated. The peptide levels were determined by radioimmunoassay. The concentrations of the striatal levels of dopamine (DA), 5-hydroxytryptamine and their acid metabolites were determined by high-performance liquid chromatography with electrochemical detection. An acute administration of cocaine (20 or 30 mg/kg i.p.) did not affect the peptide levels in the striatum or in the substantia nigra. A regimen of subchronic administration of cocaine (20 mg/kg/day for 4 days) increased the striatonigral DYN levels, without altering the levels of Met5-enkephalin or substance P. The increase in DYN levels were persistent for at least 4 days after the last dose of the subchronic administration of cocaine. The DYN levels returned to control values by 12 days after the last dose. The DA levels in the striatum were increased 30 min after a single dose of cocaine. None of the other treatments elicited any changes in DA or 5-hydroxytryptamine or their metabolites. The subchronic cocaine administration to dopaminergic denervated rats with 6-hydroxydopamine failed to evoke any increase in DYN levels in the striatum or substantia nigra. The concurrent administration of the D1 DA antagonist, SCH-23390, or the D2 DA antagonist, spiperone, to the subchronic regimen of cocaine also blocked the cocaine-induced increase in DYN levels. These results indicate that cocaine selectively enhances the synthesis or decreases the release of DYN in the striatonigral neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

  16. Platelet factor XIII increases the fibrinolytic resistance of platelet-rich clots by accelerating the crosslinking of alpha 2-antiplasmin to fibrin

    NASA Technical Reports Server (NTRS)

    Reed, G. L.; Matsueda, G. R.; Haber, E.

    1992-01-01

    Platelet clots resist fibrinolysis by plasminogen activators. We hypothesized that platelet factor XIII may enhance the fibrinolytic resistance of platelet-rich clots by catalyzing the crosslinking of alpha 2-antiplasmin (alpha 2AP) to fibrin. Analysis of plasma clot structure by polyacrylamide gel electrophoresis and immunoblotting revealed accelerated alpha 2AP-fibrin crosslinking in platelet-rich compared with platelet-depleted plasma clots. A similar study of clots formed with purified fibrinogen (depleted of factor XIII activity), isolated platelets, and specific factor XIII inhibitors indicated that this accelerated crosslinking was due to the catalytic activity of platelet factor XIII. Moreover, when washed platelets were aggregated by thrombin, there was evidence of platelet factor XIII-mediated crosslinking between platelet alpha 2AP and platelet fibrin(ogen). Specific inhibition (by a monoclonal antibody) of the alpha 2AP associated with washed platelet aggregates accelerated the fibrinolysis of the platelet aggregate. Thus in platelet-rich plasma clots, and in thrombin-induced platelet aggregates, platelet factor XIII actively formed alpha 2AP-fibrin crosslinks, which appeared to enhance the resistance of platelet-rich clots to fibrinolysis.

  17. EDD induces cell cycle arrest by increasing p53 levels.

    PubMed

    Smits, Veronique A J

    2012-02-15

    Tight regulation of p53 is essential for its central role in maintaining genome stability and tumor prevention. Here, EDD/ UBR5/hHyd, hereafter called EDD, is identified as a novel regulator of p53. Downregulation of EDD results in elevated p53 protein levels both in transformed and untransformed cells. Concomitant with a rise in p53, the levels of p21, a critical p53 target, are also elevated in these conditions. Surprisingly, EDD knockdown does not affect p53 protein stability, and p53 mRNA levels do not increase significantly upon EDD depletion. Consistent with the function of p53, EDD downregulation triggers a senescent phenotype in fibroblasts at later time points. In addition, the increased p53 levels upon EDD depletion cause a G(1) arrest, as co-depletion of EDD and p53 completely rescues this effect on cell cycle progression. PMID:22374670

  18. Increased brain nitric oxide levels following ethanol administration.

    PubMed

    Finnerty, Niall; O'Riordan, Saidhbhe L; Klamer, Daniel; Lowry, John; Pålsson, Erik

    2015-05-01

    Nitric oxide is a ubiquitous messenger molecule, which at elevated concentrations has been implicated in the pathogenesis of several neurological disorders. Its role in oxidative stress, attributed in particular to the formation of peroxynitrite, proceeds through its high affinity for the superoxide radical. Alcoholism has recently been associated with the induction of oxidative stress, which is generally defined as a shift in equilibrium between pro-oxidant and anti-oxidant species in the direction of the former. Furthermore, its primary metabolite acetaldehyde, has been extensively associated with oxidative damage related toxic effects following alcohol ingestion. The principal objective of this study was the application of long term in vivo electrochemistry (LIVE) to investigate the effect of ethanol (0.125, 0.5 and 2.0 g kg(-1)) and acetaldehyde (12.5, 50 and 200 mg kg(-1)) on NO levels in the nucleus accumbens of freely moving rats. Systemic administrations of ethanol and acetaldehyde resulted in a dose-dependent increases in NO levels, albeit with very differing time courses. Subsequent to this the effect on accumbal NO levels, of subjecting the animal to different drug combinations, was also elucidated. The nitric oxide synthase inhibitor L-NAME (20 mg kg(-1)) and acetaldehyde sequestering agent D-penicillamine (50 mg kg(-1)) both attenuated the increase in NO levels following ethanol (1 g kg(-1)) administration. Conversely, the alcohol dehydrogenase inhibitor 4-methylpyrazole (25 mg kg(-1)) and catalase inhibitor sodium azide (10 mg kg(-1)) potentiated the increase in NO levels following ethanol administration. Finally, dual inhibition of aldehyde dehydrogenase and catalase by cyanamide (25 mg kg(-1)) caused an attenuation of ethanol effects on NO levels. Taken together these data highlight a robust increase in brain NO levels following systemic alcohol administration which is dependent on NO synthase activity and may involve both alcohol- and acetaldehyde

  19. Nanogel-crosslinked nanoparticles increase the inhibitory effects of W9 synthetic peptide on bone loss in a murine bone resorption model.

    PubMed

    Sato, Toshimi; Alles, Neil; Khan, Masud; Nagano, Kenichi; Takahashi, Mariko; Tamura, Yukihiko; Shimoda, Asako; Ohya, Keiichi; Akiyoshi, Kazunari; Aoki, Kazuhiro

    2015-01-01

    We investigated the biological activity of W9, a bone resorption inhibitor peptide, using NanoClik nanoparticles as an injectable carrier, where acryloyl group-modified cholesterol-bearing pullulan (CHPOA) nanogels were crosslinked by pentaerythritol tetra (mercaptoethyl) polyoxyethylene. Thirty 5-week-old male C57BL/6J mice were fed a low calcium diet and received once-daily subcutaneous injections of the carrier alone, W9 24 mg/kg/day alone, W9 24 mg/kg/day incorporated in cholesterol bearing pullulan (CHP) nanogels, or W9 (8 and 24 mg/kg/day) incorporated in NanoClik nanoparticles for 4 days (n=5). Mice that received a normal calcium diet with NanoClik nanoparticle injections without W9 were used as a control group. Radiological analyses showed that administration of W9 24 mg/kg/day significantly prevented low calcium-induced reduction of bone mineral density in the long bones and lumbar vertebrae, but only when the NanoClik nanoparticles were used as a carrier. Histomorphometric analyses of the proximal tibiae revealed that W9 24 mg/kg/day incorporated in NanoClik nanoparticles prevented the increase in bone resorption indices induced by a low calcium diet, which was confirmed by measurement of serum bone resorption markers. These data suggest that NanoClik nanoparticles could be a useful carrier for peptide therapeutics, and also demonstrate that daily subcutaneous injections of the W9 peptide with the nanoparticles were able to inhibit bone loss in vivo. An osteoclastogenesis inhibition assay performed in vitro confirmed a slower release profile of W9 from NanoClik nanoparticles compared with conventional CHP nanogels. PMID:25999711

  20. Nanogel-crosslinked nanoparticles increase the inhibitory effects of W9 synthetic peptide on bone loss in a murine bone resorption model

    PubMed Central

    Sato, Toshimi; Alles, Neil; Khan, Masud; Nagano, Kenichi; Takahashi, Mariko; Tamura, Yukihiko; Shimoda, Asako; Ohya, Keiichi; Akiyoshi, Kazunari; Aoki, Kazuhiro

    2015-01-01

    We investigated the biological activity of W9, a bone resorption inhibitor peptide, using NanoClik nanoparticles as an injectable carrier, where acryloyl group-modified cholesterol-bearing pullulan (CHPOA) nanogels were crosslinked by pentaerythritol tetra (mercaptoethyl) polyoxyethylene. Thirty 5-week-old male C57BL/6J mice were fed a low calcium diet and received once-daily subcutaneous injections of the carrier alone, W9 24 mg/kg/day alone, W9 24 mg/kg/day incorporated in cholesterol bearing pullulan (CHP) nanogels, or W9 (8 and 24 mg/kg/day) incorporated in NanoClik nanoparticles for 4 days (n=5). Mice that received a normal calcium diet with NanoClik nanoparticle injections without W9 were used as a control group. Radiological analyses showed that administration of W9 24 mg/kg/day significantly prevented low calcium-induced reduction of bone mineral density in the long bones and lumbar vertebrae, but only when the NanoClik nanoparticles were used as a carrier. Histomorphometric analyses of the proximal tibiae revealed that W9 24 mg/kg/day incorporated in NanoClik nanoparticles prevented the increase in bone resorption indices induced by a low calcium diet, which was confirmed by measurement of serum bone resorption markers. These data suggest that NanoClik nanoparticles could be a useful carrier for peptide therapeutics, and also demonstrate that daily subcutaneous injections of the W9 peptide with the nanoparticles were able to inhibit bone loss in vivo. An osteoclastogenesis inhibition assay performed in vitro confirmed a slower release profile of W9 from NanoClik nanoparticles compared with conventional CHP nanogels. PMID:25999711

  1. Nanogel-crosslinked nanoparticles increase the inhibitory effects of W9 synthetic peptide on bone loss in a murine bone resorption model.

    PubMed

    Sato, Toshimi; Alles, Neil; Khan, Masud; Nagano, Kenichi; Takahashi, Mariko; Tamura, Yukihiko; Shimoda, Asako; Ohya, Keiichi; Akiyoshi, Kazunari; Aoki, Kazuhiro

    2015-01-01

    We investigated the biological activity of W9, a bone resorption inhibitor peptide, using NanoClik nanoparticles as an injectable carrier, where acryloyl group-modified cholesterol-bearing pullulan (CHPOA) nanogels were crosslinked by pentaerythritol tetra (mercaptoethyl) polyoxyethylene. Thirty 5-week-old male C57BL/6J mice were fed a low calcium diet and received once-daily subcutaneous injections of the carrier alone, W9 24 mg/kg/day alone, W9 24 mg/kg/day incorporated in cholesterol bearing pullulan (CHP) nanogels, or W9 (8 and 24 mg/kg/day) incorporated in NanoClik nanoparticles for 4 days (n=5). Mice that received a normal calcium diet with NanoClik nanoparticle injections without W9 were used as a control group. Radiological analyses showed that administration of W9 24 mg/kg/day significantly prevented low calcium-induced reduction of bone mineral density in the long bones and lumbar vertebrae, but only when the NanoClik nanoparticles were used as a carrier. Histomorphometric analyses of the proximal tibiae revealed that W9 24 mg/kg/day incorporated in NanoClik nanoparticles prevented the increase in bone resorption indices induced by a low calcium diet, which was confirmed by measurement of serum bone resorption markers. These data suggest that NanoClik nanoparticles could be a useful carrier for peptide therapeutics, and also demonstrate that daily subcutaneous injections of the W9 peptide with the nanoparticles were able to inhibit bone loss in vivo. An osteoclastogenesis inhibition assay performed in vitro confirmed a slower release profile of W9 from NanoClik nanoparticles compared with conventional CHP nanogels.

  2. Hyperprolactinemia during antipsychotics treatment increases the level of coagulation markers

    PubMed Central

    Ishioka, Masamichi; Yasui-Furukori, Norio; Sugawara, Norio; Furukori, Hanako; Kudo, Shuhei; Nakamura, Kazuhiko

    2015-01-01

    Objective The strong association between psychiatric patients who receive antipsychotics and the incidence of venous thromboembolism (VTE) is known. Although previous reports suggest that hyperprolactinemia often increases markers of activated coagulation, few studies have examined the direct relationship between the prolactin level elevated by antipsychotics and activated markers of activated coagulation. Method The participants included 182 patients with schizophrenia (male =89, female =93) who received antipsychotic treatments for at least 3 months. Markers of VTE (D-dimer, fibrin/fibrinogen degradation products, and thrombin–antithrombin complex) and serum prolactin concentrations were measured. Results Prolactin levels were significantly correlated with the logarithmic transformation of the D-dimer (r=0.320, P=0.002) and fibrin/fibrinogen degradation product levels (r=0.236, P=0.026) but not of the thrombin–antithrombin complex level (r=0.117, ns) among men. However, no correlations were found between the VTE markers and prolactin levels among women. These results were confirmed using multiple regression analyses that included demographic factors and antipsychotic dosages. Conclusion The current study indicates that hyperprolactinemia is associated with an increase in markers of activated coagulation among men receiving antipsychotics. This finding clinically implies that monitoring and modulating prolactin levels among men are important to decrease the risk of VTE. PMID:25750528

  3. Increased isoprostane levels in oleic acid-induced lung injury

    SciTech Connect

    Ono, Koichi; Koizumi, Tomonobu; Tsushima, Kenji; Yoshikawa, Sumiko; Yokoyama, Toshiki; Nakagawa, Rikimaru; Obata, Toru

    2009-10-16

    The present study was performed to examine a role of oxidative stress in oleic acid-induced lung injury model. Fifteen anesthetized sheep were ventilated and instrumented with a lung lymph fistula and vascular catheters for blood gas analysis and measurement of isoprostanes (8-epi prostaglandin F2{alpha}). Following stable baseline measurements, oleic acid (0.08 ml/kg) was administered and observed 4 h. Isoprostane was measured by gas chromatography mass spectrometry with the isotope dilution method. Isoprostane levels in plasma and lung lymph were significantly increased 2 h after oleic acid administration and then decreased at 4 h. The percent increases in isoprostane levels in plasma and lung lymph at 2 h were significantly correlated with deteriorated oxygenation at the same time point, respectively. These findings suggest that oxidative stress is involved in the pathogenesis of the pulmonary fat embolism-induced acute lung injury model in sheep and that the increase relates with the deteriorated oxygenation.

  4. The Importance of Non-accessible Crosslinks and Solvent Accessible Surface Distance in Modeling Proteins with Restraints From Crosslinking Mass Spectrometry.

    PubMed

    Matthew Allen Bullock, Joshua; Schwab, Jannik; Thalassinos, Konstantinos; Topf, Maya

    2016-07-01

    Crosslinking mass spectrometry (XL-MS) is becoming an increasingly popular technique for modeling protein monomers and complexes. The distance restraints garnered from these experiments can be used alone or as part of an integrative modeling approach, incorporating data from many sources. However, modeling practices are varied and the difference in their usefulness is not clear. Here, we develop a new scoring procedure for models based on crosslink data-Matched and Nonaccessible Crosslink score (MNXL). We compare its performance with that of other commonly-used scoring functions (Number of Violations and Sum of Violation Distances) on a benchmark of 14 protein domains, each with 300 corresponding models (at various levels of quality) and associated, previously published, experimental crosslinks (XLdb). The distances between crosslinked lysines are calculated either as Euclidean distances or Solvent Accessible Surface Distances (SASD) using a newly-developed method (Jwalk). MNXL takes into account whether a crosslink is nonaccessible, i.e. an experimentally observed crosslink has no corresponding SASD in a model due to buried lysines. This metric alone is shown to have a significant impact on modeling performance and is a concept that is not considered at present if only Euclidean distances are used. Additionally, a comparison between modeling with SASD or Euclidean distance shows that SASD is superior, even when factoring out the effect of the nonaccessible crosslinks. Our benchmarking also shows that MNXL outperforms the other tested scoring functions in terms of precision and correlation to Cα-RMSD from the crystal structure. We finally test the MNXL at different levels of crosslink recovery (i.e. the percentage of crosslinks experimentally observed out of all theoretical ones) and set a target recovery of ∼20% after which the performance plateaus. PMID:27150526

  5. The Importance of Non-accessible Crosslinks and Solvent Accessible Surface Distance in Modeling Proteins with Restraints From Crosslinking Mass Spectrometry.

    PubMed

    Matthew Allen Bullock, Joshua; Schwab, Jannik; Thalassinos, Konstantinos; Topf, Maya

    2016-07-01

    Crosslinking mass spectrometry (XL-MS) is becoming an increasingly popular technique for modeling protein monomers and complexes. The distance restraints garnered from these experiments can be used alone or as part of an integrative modeling approach, incorporating data from many sources. However, modeling practices are varied and the difference in their usefulness is not clear. Here, we develop a new scoring procedure for models based on crosslink data-Matched and Nonaccessible Crosslink score (MNXL). We compare its performance with that of other commonly-used scoring functions (Number of Violations and Sum of Violation Distances) on a benchmark of 14 protein domains, each with 300 corresponding models (at various levels of quality) and associated, previously published, experimental crosslinks (XLdb). The distances between crosslinked lysines are calculated either as Euclidean distances or Solvent Accessible Surface Distances (SASD) using a newly-developed method (Jwalk). MNXL takes into account whether a crosslink is nonaccessible, i.e. an experimentally observed crosslink has no corresponding SASD in a model due to buried lysines. This metric alone is shown to have a significant impact on modeling performance and is a concept that is not considered at present if only Euclidean distances are used. Additionally, a comparison between modeling with SASD or Euclidean distance shows that SASD is superior, even when factoring out the effect of the nonaccessible crosslinks. Our benchmarking also shows that MNXL outperforms the other tested scoring functions in terms of precision and correlation to Cα-RMSD from the crystal structure. We finally test the MNXL at different levels of crosslink recovery (i.e. the percentage of crosslinks experimentally observed out of all theoretical ones) and set a target recovery of ∼20% after which the performance plateaus.

  6. Endozepine-4 levels are increased in hepatic coma

    PubMed Central

    Malaguarnera, Giulia; Vacante, Marco; Drago, Filippo; Bertino, Gaetano; Motta, Massimo; Giordano, Maria; Malaguarnera, Michele

    2015-01-01

    AIM: To evaluate the serum levels of endozepine-4, their relation with ammonia serum levels, the grading of coma and the severity of cirrhosis, in patients with hepatic coma. METHODS: In this study we included 20 subjects with Hepatic coma, 20 subjects with minimal hepatic encephalopathy (MHE) and 20 subjects control. All subjects underwent blood analysis, Child Pugh and Model for End - stage liver disease (MELD) assessment, endozepine-4 analysis. RESULTS: Subjects with hepatic coma showed significant difference in endozepine-4 (P < 0.001) and NH3 levels (P < 0.001) compared both to MHE and controls patients. Between NH3 and endozepine-4 we observed a significant correlation (P = 0.009; Pearson correlation 0.570). There was a significant correlation between endozepine-4 and MELD (P = 0.017; Pearson correlation = 0.529). In our study blood ammonia concentration was noted to be raised in patients with hepatic coma, with the highest ammonia levels being found in those who were comatose. We also found a high correlation between endozepine-4 and ammonia (P < 0.001). In patients with grade IV hepatic coma, endozepine levels were significantly higher compared to other groups. CONCLUSION: This study suggests that an increased level of endozepine in subjects with higher levels of MELD was observed. In conclusion, data concerning involvement of the GABA-ergic system in HE coma could be explained by stage-specific alterations. PMID:26290636

  7. Increasing carbonmonoxide blood levels in Bangkok bus drivers

    SciTech Connect

    Saenghirunvattana, S.; Wananukul, W.; Mokkhavesa, C.; Opasi, N.

    1995-05-01

    In order to study the effects of air pollution in Bangkok, 31 bus drivers were examined and blood was drawn for measurement of carboxyhemoglobin (COHb) prior to and after work. The COHb level before work was 2.19{+-}2.46% (range 0.7.18). It had increased after work to 5.26{+-}2.52% (range 0-10.4) (p<0.001). Twenty-one drivers complained of chronic headaches, myalgia, and eye irritation during working hours. The COHb level was not statistically different between smokers and nonsmokers.

  8. Elevated levels of STAT1 in Fanconi anemia group A lymphoblasts correlate with the cells’ sensitivity to DNA interstrand crosslinking drugs

    PubMed Central

    Prieto-Remón, Inés; Sánchez-Carrera, Dámaso; López-Duarte, Mónica; Richard, Carlos; Pipaón, Carlos

    2013-01-01

    Progressive bone marrow failure starting in the first decade of life is one of the main characteristics of Fanconi anemia. Along with the bone marrow failure, this pathology is characterized by congenital malformations, endocrine dysfunction and an extraordinary predisposition to develop cancer. The fact that hematopoietic progenitor cells from subjects with Fanconi anemia are sensitive to both DNA-interstrand crosslinking agents and inflammatory cytokines, which are aberrantly overproduced in these patients, has led to different explanations for the causes of the bone marrow failure. We analyzed STAT1 expression in lymphoblastoid cell lines derived from patients with Fanconi anemia group A and correlated this with aspects of the Fanconi anemia phenotype such as sensitivity to genotoxic agents or to inhibitory cytokines. We provide evidence of overexpression of STAT1 in FANCA-deficient cells which has both transcriptional and post-translational components, and is related to the constitutive activation of ERK in Fanconi anemia group A cells, since it can be reverted by treatment with U0126. STAT1 phosphorylation was not defective in the lymphoblasts, so these cells accumulated higher levels of active STAT1 in response to interferon gamma, probably in relation to their greater sensitivity to this cytokine. On the other hand, inhibition of STAT1 by genetic or chemical means reverted the hypersensitivity of Fanconi anemia group A lymphoblasts to DNA interstrand crosslinking agents. Our data provide an explanation for the mixed sensitivity of Fanconi anemia group A cells to both genotoxic stress and inflammatory cytokines and indicate new targets for the treatment of bone marrow failure in these patients. PMID:23585528

  9. Methamphetamine increases basal ganglia iron to levels observed in aging.

    PubMed

    Melega, William P; Laćan, Goran; Harvey, Dennis C; Way, Baldwin M

    2007-10-29

    Increases in basal ganglia iron are well documented for neurodegenerative diseases but have not been associated with methamphetamine (METH). In this study, vervet monkeys that received two doses of METH (2 mg/kg, intramuscularly, 6 h apart) showed at 1 month, iron increases in substantia nigra pars reticulata and globus pallidus, with concurrent increases of ferritin-immunoreactivity and decreases of tyrosine hydroxylase-immunoreactivity in substantia nigra. At 1.5 years, substantia nigra tyrosine hydroxylase-immunoreactivity had recovered while iron and ferritin-immunoreactivity increases persisted. Globus pallidus and substantia nigra iron levels of the adult METH-exposed animals (age 5-9 years) were now comparable with those of drug-naive, aged animals (19-22 years), suggesting an aging-related condition that might render those regions more vulnerable to oxidative stress.

  10. Increased plasma levels of interleukin-6 in sepsis.

    PubMed

    Hack, C E; De Groot, E R; Felt-Bersma, R J; Nuijens, J H; Strack Van Schijndel, R J; Eerenberg-Belmer, A J; Thijs, L G; Aarden, L A

    1989-10-01

    Interleukin-6 (IL-6) is likely to be an important mediator of the inflammatory response. We measured levels of this cytokine in plasma samples from 37 patients with sepsis or septic shock obtained at the time of admission to the intensive care unit and related these levels to hemodynamic and biochemical parameters as well as to clinical outcome. In 32 of the 37 patients, increased levels of IL-6 were found, occasionally up to 7,500 times the normal level. The highest IL-6 levels were encountered in patients who suffered from septic shock (P value of the difference between patients with and without shock less than .0001). In addition, IL-6 significantly correlated with plasma lactate (P less than .0001), heart rate (P = .05) and, inversely, with mean arterial pressure (P = .01) and platelet counts (P = .0002). Significant correlations of IL-6 with the anaphylatoxins C3a (P = .0001) and C4a (P = .0002) and with the main inhibitor of the classical pathway of complement, C1-inhibitor (inverse correlation, P = .05), were also observed. IL-6 on admission appeared to be of prognostic significance: levels were higher in septic patients who subsequently died than in those who survived (P = .0003), in particular when only patients with septic shock were considered (P less than .0001). All nine septic patients with levels of less than 40 U/mL on admission survived, whereas 89% of the nine patients with levels exceeding 7,500 U/mL died. These data provide evidence for a role of IL-6 in the pathophysiology of septic shock. Further studies are needed to reveal whether IL-6 in sepsis is directly involved in mediating lethal complications or whether it is to be considered as an "alarm hormone" that reflects endothelial cell injury probably mediated by the anaphylatoxines.

  11. Increased plasma homocysteine levels in shift working bus drivers

    PubMed Central

    Martins, P; D'Almeida, V; Vergani, N; Perez, A; Tufik, S

    2003-01-01

    Background: Previous studies have indicated an association between shift work and cardiovascular disease. There is also considerable epidemiological evidence that hyperhomocysteinemia is an independent risk factor for cardiovascular disorders. Aims: To analyse plasma homocysteine levels in shift work bus drivers, and to investigate possible relations with sleep parameters and other biochemical factors. Methods: Blood samples were collected from 30 male shift working long-haul bus drivers in a Brazilian sample and analysed for plasma levels of homocysteine, folic acid, vitamin B12, and serum lipids. A group of 22 daytime workers, matched for age and body mass index served as controls. The incidence of mutations in the gene coding for methylene tetrahydrofolate, an enzyme which is related to hyperhomocysteinemia, was also assessed. Polysomnographic recordings were obtained from the target group. Results: Bus drivers showed significantly higher levels of plasma homocysteine than the control group (18.57 v 9.43 µM). Most of the other biochemical, behavioural, and molecular parameters did not differ between groups. Likewise, sleep parameters appeared to be within the normal range. Conclusions: The significantly increased plasma homocysteine levels in long-haul bus drivers did not appear to be secondary to other biochemical or behavioural problems in this group. These results suggest that hyperhomocysteinemia may be involved in the increased incidence of cardiovascular diseases observed in shift workers. PMID:12937187

  12. Placental Cadmium Levels Are Associated with Increased Preeclampsia Risk

    PubMed Central

    Laine, Jessica E.; Ray, Paul; Bodnar, Wanda; Cable, Peter H.; Boggess, Kim; Offenbacher, Steven; Fry, Rebecca C.

    2015-01-01

    Environmental exposure to heavy metals is a potentially modifiable risk factor for preeclampsia (PE). Toxicologically, there are known interactions between the toxic metal cadmium (Cd) and essential metals such as selenium (Se) and zinc (Zn), as these metals can protect against the toxicity of Cd. As they relate to preeclampsia, the interaction between Cd and these essential metals is unknown. The aims of the present study were to measure placental levels of Cd, Se, and Zn in a cohort of 172 pregnant women from across the southeast US and to examine associations of metals levels with the odds of PE in a nested case-control design. Logistic regressions were performed to assess odds ratios (OR) for PE with exposure to Cd controlling for confounders, as well as interactive models with Se or Zn. The mean placental Cd level was 3.6 ng/g, ranging from 0.52 to 14.5 ng/g. There was an increased odds ratio for PE in relationship to placental levels of Cd (OR = 1.5; 95% CI: 1.1–2.2). The Cd-associated OR for PE increased when analyzed in relationship to lower placental Se levels (OR = 2.0; 95% CI: 1.1–3.5) and decreased with higher placental Se levels (OR = 0.98; 95% CI: 0.5–1.9). Similarly, under conditions of lower placental Zn, the Cd-associated OR for PE was elevated (OR = 1.8; 95% CI: 0.8–3.9), whereas with higher placental Zn it was reduced (OR = 1.3; 95% CI: 0.8–2.0). Data from this pilot study suggest that essential metals may play an important role in reducing the odds of Cd-associated preeclampsia and that replication in a larger cohort is warranted. PMID:26422011

  13. Increases in Mitochondrial Biogenesis Impair Carcinogenesis at Multiple Levels

    PubMed Central

    Wang, Xiao; Moraes, Carlos T.

    2011-01-01

    Although mitochondrial respiration is decreased in most cancer cells, the role of this decrease in carcinogenesis and cancer progression is still unclear. To better understand this phenomenon, instead of further inhibiting mitochondrial function, we induced mitochondrial biogenesis in transformed cells by activating the peroxisome proliferator-activated receptors (PPARs)/ peroxisome proliferator-activated receptor gamma co-activator 1α (PGC-1α) pathways. This was achieved by treating the cells with bezafibrate, a PPARs panagonist that also enhances PGC-1α expression. We confirmed that bezafibrate treatment led to increased mitochondrial proteins and enzyme functions. We found that cells with increased mitochondrial biogenesis had decreased growth rates in glucose-containing medium. In addition, they became less invasive, which was directly linked to the reduced lactate levels. Surprisingly, even though bezafibrate-treated cells had higher levels of mitochondrial markers, total respiration was not significantly altered. However, respiratory coupling, and ATP levels were. Our data show that by increasing the efficiency of the mitochondrial oxidative phosphorylation system, cancer progression is hampered by decreases in cell proliferation and invasiveness. PMID:21855427

  14. Experimentally increased noise levels change spatial and singing behaviour

    PubMed Central

    McLaughlin, Kirsty Elizabeth; Kunc, Hansjoerg P.

    2013-01-01

    The reasons why animal populations decline in response to anthropogenic noise are still poorly understood. To understand how populations are affected by noise, we must understand how individuals are affected by noise. By modifying the acoustic environment experimentally, we studied the potential relationship between noise levels and both spatial and singing behaviour in the European robin (Erithacus rubecula). We found that with increasing noise levels, males were more likely to move away from the noise source and changed their singing behaviour. Our results provide the first experimental evidence in a free ranging species, that not merely the presence of noise causes changes in behaviour and distribution, but that the level of noise pollution plays a crucial role as well. Our results have important implications for estimating the impact of infrastructure which differs in the level of noise produced. Thus, governmental planning bodies should not only consider the physical effect on the landscape when assessing the impact of new infrastructure, but also the noise levels emitted, which may reduce the loss of suitable habitats available for animals. PMID:23173189

  15. Decreased training volume and increased carbohydrate intake increases oxidized LDL levels.

    PubMed

    Välimäki, I A; Vuorimaa, T; Ahotupa, M; Kekkonen, R; Korpela, R; Vasankari, T

    2012-04-01

    We studied effects of probiotics and training volume on oxidized LDL lipids (ox-LDL), serum antioxidant potential (s-TRAP) and serum antioxidants (s-α-tocopherol, s-γ-tocopherol, s-retinol, s-β-carotene and s-ubiquinone-10) in marathon runners during 3-months training period, 6-days preparation period and marathon run. Runners (n=127) were recruited for a randomized, double-blind intervention during which they received either Lactobacillus rhamnosus GG (LGG, probiotic group) or placebo drink (placebo group) during whole study. During the preparation period, subjects decreased training and increased carbohydrate intake. Blood samples were taken at baseline, before 6-days preparation, before and immediately after the marathon. Probiotics did not have any effect on ox-LDL, s-TRAP or serum antioxidants levels during the study. Interestingly, ox-LDL increased by 28% and 33% during the preparation period and decreased by 16% and 19% during the marathon run in the placebo and probiotic groups, respectively (in all, P<0.001). No changes were seen in s-TRAP before marathon, but during run s-TRAP raised by 16% in both groups (both, P<0.001). The increase of ox-LDL level during the preparative period after several months' training suggests that aerobic training may reduce the concentration of ox-LDL and that decrease of training together with increased energy intake, mainly carbohydrate, before marathon is capable of increasing the level of ox-LDL.

  16. Hydrocellular foam dressing increases the leptin level in wound fluid.

    PubMed

    Yoshino, Sawako; Nakagami, Gojiro; Ohira, Tomomi; Kawasaki, Rui; Shimura, Mari; Iwatsuki, Ken; Sanada, Hiromi; Kobayashi-Hattori, Kazuo; Oishi, Yuichi; Yamane, Takumi

    2015-09-01

    Hydrocellular foam dressing (HCF) absorbs excessive wound fluid, which contains various cytokines and growth factors, and ensures a moist environment to promote wound healing. However, the molecular mechanisms underlying the wound fluid component changes induced by HCF are poorly understood. In the present study, we examined the effect of HCF on wound healing and the associated regulatory mechanisms in relation to variations in cytokine levels in the wound fluid. We created full-thickness wounds on the dorsolateral skin of rats and collected the resulting wound fluid samples. HCF was immersed in a plate containing the wound fluids. HCF was then removed and the excess wound fluid remaining in the plate was examined by cytokine array and enzyme-linked immunosorbent assay. We also used a rat model and human dermal fibroblast cultures to examine the effect of wound fluid component changes during the wound healing process. Upon treatment with HCF, leptin levels were upregulated in the wound fluid. Fibroblast proliferation was enhanced and the effect was suppressed in the presence of leptin antagonist. In our in vivo model, HCF increased wound contraction compared with film dressings and this positive effect of HCF was suppressed by addition of leptin antagonist. Our results suggest that dermal fibroblast proliferation is upregulated by HCF due to increased leptin level at the wound surface, and these effects promote wound healing. We believe that the present study contributes to furthering the understanding of the mechanisms underlying the effects of HCF-induced wound healing.

  17. A Three Level Autonomous Software System for Increased Science Return

    NASA Astrophysics Data System (ADS)

    Robinson, P. I.; Mancinelli, R. L.; Landheim, R.

    2005-12-01

    The development of smart science instruments for autonomous operation (on Earth or in space) has the potential to increase science return and reduce the risk of experiment failure. When researchers are confronted with unexpected data/results of the experimental test system, they must determine whether the experimental setup has failed, or scientific discovery is being made. These two classes of events could have the same time series signature. To directly address this issue, we have developed a three-level software system referred to as E3, which consists of an engineering level, an experiment level, and an executive level. Each level of the software system is designed in a modular fashion using model based feedback controllers. The same feedback control mechanism is used for each level; the model itself determines the level. To determine if failure of the experimental setup can explain the data/results, researchers run calibration tests for hardware (e.g., sensors and actuators) as well as verify that the software (e.g., controls and analog to digital conversion routines) is running as planned. If anomalies are found, then modifications are made to the experimental setup, or the anomaly is accepted as the new baseline state of the instrument. The engineering level of the E3 software system is responsible for this process. To determine if scientific discovery, as opposed to failure, can explain the data/results, a researcher tries to explain the difference between the observed and expected results. These explanations are terms of the basic processes of nature to determine the rate limiting step(s) of a complex set of processes, where the flux could be due to heat transfer, mass transfer, momentum transfer, or chemical reaction processes. Once the differences are understood, modifications are made to the software control of the experiment, as well as to the model the researcher is building over the course of repeated experiments. The experiment level of the E3

  18. Genistein increases glycosaminoglycan levels in mucopolysaccharidosis type I cell models.

    PubMed

    Kingma, Sandra D K; Wagemans, Tom; IJlst, Lodewijk; Wijburg, Frits A; van Vlies, Naomi

    2014-09-01

    Mucopolysaccharidosis type I (MPS I) is a lysosomal storage disorder characterized by diminished degradation of the glycosaminoglycans (GAGs) heparan sulfate and dermatan sulfate, which results in the accumulation of these GAGs and subsequent cellular dysfunction. Patients present with a variety of symptoms, including severe skeletal disease. Genistein has been shown previously to inhibit GAG synthesis in MPS fibroblasts, presumably through inhibition of tyrosine kinase activity of the epidermal growth factor receptor (EGFR). To determine the potentials of genistein for the treatment of skeletal disease, MPS I fibroblasts were induced into chondrocytes and osteoblasts and treated with genistein. Surprisingly, whereas tyrosine phosphorylation levels (as a measure for tyrosine kinase inhibition) were decreased in all treated cell lines, there was a 1.3 and 1.6 fold increase in GAG levels in MPS I chondrocytes and fibroblast, respectively (p < 0.05). Sulfate incorporation in treated MPS I fibroblasts was 2.6 fold increased (p < 0.05), indicating increased GAG synthesis despite tyrosine kinase inhibition. This suggests that GAG synthesis is not exclusively regulated through the tyrosine kinase activity of the EGFR. We hypothesize that the differences in outcomes between studies on the effect of genistein in MPS are caused by the different effects of genistein on different growth factor signaling pathways, which regulate GAG synthesis. More studies are needed to elucidate the precise signaling pathways which are affected by genistein and alter GAG metabolism in order to evaluate the therapeutic potential of genistein for MPS patients. PMID:24699889

  19. Increased levels of metallothionein in placenta of smokers.

    PubMed

    Ronco, Ana Maria; Arguello, Graciela; Suazo, Myriam; Llanos, Miguel N

    2005-03-01

    Experiments were designed to evaluate and compare metallothionein (MT), zinc and cadmium levels in human placentas of smoking and non-smoking women. Smoking was assessed by self-reported cigarette consumption and urine cotinine levels before delivery. Smoking pregnant women with urine cotinine levels higher than 130 ng/ml were included in the smoking group. Determination of placental MT was performed by western blot analysis after tissue homogenization and saturation with cadmium chloride (1000 ppm). Metallothionein was analyzed with a monoclonal antibody raised against MT-1 and MT-2 and with a second anti mouse antibody conjugated to alkaline phosphatase. Zinc and cadmium were determined by neutron activation analysis and atomic absorption spectrometry respectively. Smokers showed higher placental MT and cadmium levels, together with decreased newborn birth weights, as compared to non-smokers. The semi-quantitative analysis of western blots by band densitometry indicated that darker bands corresponded to MT present in smokers' samples. This study confirms that cigarette smoking increases cadmium accumulation in placental tissue and suggests that this element has a stimulatory effect on placental MT production.

  20. [Human tolerance to rotation at different levels of increased gravitation].

    PubMed

    Genin, A M; Kotovskaia, A R; Galle, R R; Gavrilova, L N; Sarkisov, I Iu

    1982-01-01

    The effects of acceleration of different value (up to 2 g) on the level of motion sickness, vestibular and postural reactions to rotation were studied. The experiments were carried out in a centrifuge equipped with a cabin that could be mounted at a different distance from the axis of rotation. Three experimental runs were conducted with a rate of rotation of 15.3 and accelerations values of 1.09, 1.6 and 2.0 g. Vestibular stimulation was produced by head movements of a predetermined number. It was found that with increase in the acceleration value the level of motion sickness decreased and the nystagmic reaction and balance dysfunction enhanced. PMID:6977679

  1. Increased dopamine level enhances male-male courtship in Drosophila.

    PubMed

    Liu, Tong; Dartevelle, Laurence; Yuan, Chunyan; Wei, Hongping; Wang, Ying; Ferveur, Jean-François; Guo, Aike

    2008-05-21

    Sexual behavior between males is observed in many species, but the biological factors involved are poorly known. In mammals, manipulation of dopamine has revealed the role of this neuromodulator on male sexual behavior. We used genetic and pharmacological approaches to manipulate the dopamine level in dopaminergic cells in Drosophila and investigated the consequence of this manipulation on male-male courtship behavior. Males with increased dopamine level showed enhanced propensity to court other males but did not change their courtship toward virgin females, general olfactory response, general gustatory response, or locomotor activity. Our results indicate that the high intensity of male-male interaction shown by these manipulated males was related to their altered sensory perception of other males.

  2. Increased dopamine level enhances male-male courtship in Drosophila.

    PubMed

    Liu, Tong; Dartevelle, Laurence; Yuan, Chunyan; Wei, Hongping; Wang, Ying; Ferveur, Jean-François; Guo, Aike

    2008-05-21

    Sexual behavior between males is observed in many species, but the biological factors involved are poorly known. In mammals, manipulation of dopamine has revealed the role of this neuromodulator on male sexual behavior. We used genetic and pharmacological approaches to manipulate the dopamine level in dopaminergic cells in Drosophila and investigated the consequence of this manipulation on male-male courtship behavior. Males with increased dopamine level showed enhanced propensity to court other males but did not change their courtship toward virgin females, general olfactory response, general gustatory response, or locomotor activity. Our results indicate that the high intensity of male-male interaction shown by these manipulated males was related to their altered sensory perception of other males. PMID:18495888

  3. Can nursing students' confidence levels increase with repeated simulation activities?

    PubMed

    Cummings, Cynthia L; Connelly, Linda K

    2016-01-01

    In 2014, nursing faculty conducted a study with undergraduate nursing students on their satisfaction, confidence, and educational practice levels, as it related to simulation activities throughout the curriculum. The study was a voluntary survey conducted on junior and senior year nursing students. It consisted of 30 items based on the Student Satisfaction and Self-Confidence in Learning and the Educational Practices Questionnaire (Jeffries, 2012). Mean averages were obtained for each of the 30 items from both groups and were compared using T scores for unpaired means. The results showed that 8 of the items had a 95% confidence level and when combined the items were significant for p <.001. The items identified were those related to self-confidence and active learning. Based on these findings, it can be assumed that repeated simulation experiences can lead to an increase in student confidence and active learning. PMID:26599594

  4. Can nursing students' confidence levels increase with repeated simulation activities?

    PubMed

    Cummings, Cynthia L; Connelly, Linda K

    2016-01-01

    In 2014, nursing faculty conducted a study with undergraduate nursing students on their satisfaction, confidence, and educational practice levels, as it related to simulation activities throughout the curriculum. The study was a voluntary survey conducted on junior and senior year nursing students. It consisted of 30 items based on the Student Satisfaction and Self-Confidence in Learning and the Educational Practices Questionnaire (Jeffries, 2012). Mean averages were obtained for each of the 30 items from both groups and were compared using T scores for unpaired means. The results showed that 8 of the items had a 95% confidence level and when combined the items were significant for p <.001. The items identified were those related to self-confidence and active learning. Based on these findings, it can be assumed that repeated simulation experiences can lead to an increase in student confidence and active learning.

  5. Viscoelastic behavior of polymers undergoing crosslinking reactions.

    NASA Technical Reports Server (NTRS)

    Moacanin, J.; Aklonis, J. J.

    1971-01-01

    Previously a method was developed for predicting the viscoelastic response of polymers undergoing scission reactions. These results are now extended to include crosslinking reactions. As for scission, at any given time the character of the network chains is determined by the instantaneous crosslink density. For scission all chains were assumed to carry the same stress; for crosslinking, however, the stress is distributed between the 'new' and 'old' chains. Equations for calculating the creep response of a system which experiences a step increase in crosslink density are derived.

  6. Exercise Increases Serum Fibroblast Growth Factor 21 (FGF21) Levels

    PubMed Central

    Cuevas-Ramos, Daniel; Almeda-Valdés, Paloma; Meza-Arana, Clara Elena; Brito-Córdova, Griselda; Gómez-Pérez, Francisco J.; Mehta, Roopa; Oseguera-Moguel, Jorge; Aguilar-Salinas, Carlos A.

    2012-01-01

    Background Fibroblast growth factor 21 (FGF21) increases glucose uptake. It is unknown if FGF21 serum levels are affected by exercise. Methodology/Principal Findings This was a comparative longitudinal study. Anthropometric and biochemical evaluation were carried out before and after a bout of exercise and repeated after two weeks of daily supervised exercise. The study sample was composed of 60 sedentary young healthy women. The mean age was 24±3.7 years old, and the mean BMI was 21.4±7.0 kg/m2. The anthropometric characteristics did not change after two weeks of exercise. FGF21 levels significantly increased after two weeks of exercise (276.8 ng/l (142.8–568.6) vs. (460.8 (298.2–742.1), p<0.0001)). The delta (final–basal) log of serum FGF21, adjusted for BMI, showed a significant positive correlation with basal glucose (r = 0.23, p = 0.04), mean maximal heart rate (MHR) (r = 0.54, p<0.0001), mean METs (r = 0.40, p = 0.002), delta plasma epinephrine (r = 0.53, p<0.0001) and delta plasma FFAs (r = 0.35, p = 0.006). A stepwise linear regression model showed that glucose, MHR, METs, FFAs, and epinephrine, were factors independently associated with the increment in FGF21 after the exercise program (F = 4.32; r2 = 0.64, p<0.0001). Conclusions Serum FGF21 levels significantly increased after two weeks of physical activity. This increment correlated positively with clinical parameters related to the adrenergic and lipolytic response to exercise. Trial Registration ClinicalTrials.gov NCT01512368 PMID:22701542

  7. Co-ruminating increases stress hormone levels in women.

    PubMed

    Byrd-Craven, Jennifer; Geary, David C; Rose, Amanda J; Ponzi, Davide

    2008-03-01

    Same-sex friendships are an important source of social support and typically contribute to positive adjustment. However, there can be adjustment trade-offs if the friends co-ruminate (i.e., talk excessively about problems) in that co-rumination is related to having close friendships but also to increased internalizing symptoms. The current study utilized an experimental manipulation that elicited co-rumination in young women and thus mirrored an everyday response to stress. Observed co-rumination was associated with a significant increase in the stress hormone, cortisol (after controlling for self-reported co-rumination and for cortisol levels assessed before the discussion of problems). These findings suggest that co-rumination can amplify, rather than mitigate, the hormonal stress response to personal life stressors.

  8. Can increased atmospheric CO2 levels trigger a runaway greenhouse?

    PubMed

    Ramirez, Ramses M; Kopparapu, Ravi Kumar; Lindner, Valerie; Kasting, James F

    2014-08-01

    Recent one-dimensional (globally averaged) climate model calculations by Goldblatt et al. (2013) suggest that increased atmospheric CO(2) could conceivably trigger a runaway greenhouse on present Earth if CO(2) concentrations were approximately 100 times higher than they are today. The new prediction runs contrary to previous calculations by Kasting and Ackerman (1986), which indicated that CO(2) increases could not trigger a runaway, even at Venus-like CO(2) concentrations. Goldblatt et al. argued that this different behavior is a consequence of updated absorption coefficients for H(2)O that make a runaway more likely. Here, we use a 1-D climate model with similar, up-to-date absorption coefficients, but employ a different methodology, to show that the older result is probably still valid, although our model nearly runs away at ∼12 preindustrial atmospheric levels of CO(2) when we use the most alarmist assumptions possible. However, we argue that Earth's real climate is probably stable given more realistic assumptions, although 3-D climate models will be required to verify this result. Potential CO(2) increases from fossil fuel burning are somewhat smaller than this, 10-fold or less, but such increases could still cause sufficient warming to make much of the planet uninhabitable by humans.

  9. Can increased atmospheric CO2 levels trigger a runaway greenhouse?

    PubMed

    Ramirez, Ramses M; Kopparapu, Ravi Kumar; Lindner, Valerie; Kasting, James F

    2014-08-01

    Recent one-dimensional (globally averaged) climate model calculations by Goldblatt et al. (2013) suggest that increased atmospheric CO(2) could conceivably trigger a runaway greenhouse on present Earth if CO(2) concentrations were approximately 100 times higher than they are today. The new prediction runs contrary to previous calculations by Kasting and Ackerman (1986), which indicated that CO(2) increases could not trigger a runaway, even at Venus-like CO(2) concentrations. Goldblatt et al. argued that this different behavior is a consequence of updated absorption coefficients for H(2)O that make a runaway more likely. Here, we use a 1-D climate model with similar, up-to-date absorption coefficients, but employ a different methodology, to show that the older result is probably still valid, although our model nearly runs away at ∼12 preindustrial atmospheric levels of CO(2) when we use the most alarmist assumptions possible. However, we argue that Earth's real climate is probably stable given more realistic assumptions, although 3-D climate models will be required to verify this result. Potential CO(2) increases from fossil fuel burning are somewhat smaller than this, 10-fold or less, but such increases could still cause sufficient warming to make much of the planet uninhabitable by humans. PMID:25061956

  10. Acute stress induces increases in salivary IL-10 levels.

    PubMed

    Szabo, Yvette Z; Newton, Tamara L; Miller, James J; Lyle, Keith B; Fernandez-Botran, Rafael

    2016-09-01

    The purpose of this study was to investigate the stress-reactivity of the anti-inflammatory cytokine, IL-10, in saliva and to determine how salivary IL-10 levels change in relation to those of IL-1β, a pro-inflammatory cytokine, following stress. Healthy young adults were randomly assigned to retrieve a negative emotional memory (n = 46) or complete a modified version of the Trier Social Stress Test (n = 45). Saliva samples were taken 10 min before (baseline) and 50 min after (post-stressor) onset of a 10-min stressor, and were assayed using a high sensitivity multiplex assay for cytokines. Measurable IL-10 levels (above the minimum detectable concentration) were found in 96% of the baseline samples, and 98% of the post-stressor samples. Flow rate-adjusted salivary IL-10 levels as well as IL-1β/IL-10 ratios showed moderate but statistically significant increases in response to stress. Measurement of salivary IL-10 and pro-/anti-inflammatory cytokine ratios may be useful, noninvasive tools, in stress research.

  11. [Increased serum PIVKA-II levels in hyperthyroidism].

    PubMed

    Morimoto, M; Takeda, K; Ohara, E; Nishimori, Y; Hisahara, T; Nishida, M; Sugiura, T

    2001-11-01

    PIVKA-II has been practically used as a tumor marker of hepatocellular carcinoma. On the other hand, increased serum PIVKA-II concentration was reported in a Japanese patient who had hyperthyroidism without liver diseases. To evaluate whether thyroid hormone is related with serum PIVKA-II, we examined serum PIVKA-II concentrations in patients with various thyroid diseases. Eight patients with Hashimoto disease, 24 patients with Graves' disease, and 8 healthy subjects were studied. There was no significant difference of serum PIVKA-II levels among the three groups. However, serum PIVKA-II concentrations(mean +/- SD mAU/ml) in hyperthyroidism(37 +/- 27) were significantly higher than those in hypothyroidism(16 +/- 9) and normal controls(12 +/- 4) (p < 0.05 and p < 0.01, respectively). When hyperthyroid patients were treated by antithyroid drug or isotope, serum PIVKA-II concentrations decreased in accordance with the decrease of serum FT4 concentrations. Our data indicate that serum PIVKA-II concentration was increased in patients with hyperthyroidism, but further in vivo studies are necessary to clarify the mechanism related to increased serum PIVKA-II by thyroid hormone.

  12. Collagen and elastin cross-linking is altered during aberrant late lung development associated with hyperoxia.

    PubMed

    Mižíková, Ivana; Ruiz-Camp, Jordi; Steenbock, Heiko; Madurga, Alicia; Vadász, István; Herold, Susanne; Mayer, Konstantin; Seeger, Werner; Brinckmann, Jürgen; Morty, Rory E

    2015-06-01

    Maturation of the lung extracellular matrix (ECM) plays an important role in the formation of alveolar gas exchange units. A key step in ECM maturation is cross-linking of collagen and elastin, which imparts stability and functionality to the ECM. During aberrant late lung development in bronchopulmonary dysplasia (BPD) patients and animal models of BPD, alveolarization is blocked, and the function of ECM cross-linking enzymes is deregulated, suggesting that perturbed ECM cross-linking may impact alveolarization. In a hyperoxia (85% O2)-based mouse model of BPD, blunted alveolarization was accompanied by alterations to lung collagen and elastin levels and cross-linking. Total collagen levels were increased (by 63%). The abundance of dihydroxylysinonorleucine collagen cross-links and the dihydroxylysinonorleucine-to-hydroxylysinonorleucine ratio were increased by 11 and 18%, respectively, suggestive of a profibrotic state. In contrast, insoluble elastin levels and the abundance of the elastin cross-links desmosine and isodesmosine in insoluble elastin were decreased by 35, 30, and 21%, respectively. The lung collagen-to-elastin ratio was threefold increased. Treatment of hyperoxia-exposed newborn mice with the lysyl oxidase inhibitor β-aminopropionitrile partially restored normal collagen levels, normalized the dihydroxylysinonorleucine-to-hydroxylysinonorleucine ratio, partially normalized desmosine and isodesmosine cross-links in insoluble elastin, and partially restored elastin foci structure in the developing septa. However, β-aminopropionitrile administration concomitant with hyperoxia exposure did not improve alveolarization, evident from unchanged alveolar surface area and alveoli number, and worsened septal thickening (increased by 12%). These data demonstrate that collagen and elastin cross-linking are perturbed during the arrested alveolarization of developing mouse lungs exposed to hyperoxia.

  13. Towards engineering increased pantothenate (vitamin B(5)) levels in plants.

    PubMed

    Chakauya, Ereck; Coxon, Katy M; Wei, Ma; Macdonald, Mary V; Barsby, Tina; Abell, Chris; Smith, Alison G

    2008-11-01

    Pantothenate (vitamin B(5)) is the precursor of the 4'-phosphopantetheine moiety of coenzyme A and acyl-carrier protein. It is made by plants and microorganisms de novo, but is a dietary requirement for animals. The pantothenate biosynthetic pathway is well-established in bacteria, comprising four enzymic reactions catalysed by ketopantoate hydroxymethyltransferase (KPHMT), L: -aspartate-alpha-decarboxylase (ADC), pantothenate synthetase (PS) and ketopantoate reductase (KPR) encoded by panB, panD, panC and panE genes, respectively. In higher plants, the genes encoding the first (KPHMT) and last (PS) enzymes have been identified and characterised in several plant species. Commercially, pantothenate is chemically synthesised and used in vitamin supplements, feed additives and cosmetics. Biotransformation is an attractive alternative production system that would circumvent the expensive procedures of separating racemic intermediates. We explored the possibility of manipulating pantothenate biosynthesis in plants. Transgenic oilseed rape (Brassica napus) lines were generated in which the E. coli KPHMT and PS genes were expressed under a strong constitutive CaMV35SS promoter. No significant change of pantothenate levels in PS transgenic lines was observed. In contrast plants expressing KPHMT had elevated pantothenate levels in leaves, flowers siliques and seed in the range of 1.5-2.5 fold increase compared to the wild type plant. Seeds contained the highest vitamin content, indicating that they might be the ideal target for production purposes.

  14. Artificially Increased Yolk Hormone Levels and Neophobia in Domestic Chicks.

    PubMed

    Bertin, Aline; Arnould, Cécile; Moussu, Chantal; Meurisse, Maryse; Constantin, Paul; Leterrier, Christine; Calandreau, Ludovic

    2015-01-01

    In birds there is compelling evidence that the development and expression of behavior is affected by maternal factors, particularly via variation in yolk hormone concentrations of maternal origin. In the present study we tested whether variation in yolk hormone levels lead to variation in the expression of neophobia in young domestic chicks. Understanding how the prenatal environment could predispose chicks to express fear-related behaviors is essential in order to propose preventive actions and improve animal welfare. We simulated the consequences of a maternal stress by experimentally enhancing yolk progesterone, testosterone and estradiol concentrations in hen eggs prior to incubation. The chicks from these hormone-treated eggs (H) and from sham embryos (C) that received the vehicle-only were exposed to novel food, novel object and novel environment tests. H chicks approached a novel object significantly faster and were significantly more active in a novel environment than controls, suggesting less fearfulness. Conversely, no effect of the treatment was found in food neophobia tests. Our study highlights a developmental influence of yolk hormones on a specific aspect of neophobia. The results suggest that increased yolk hormone levels modulate specifically the probability of exploring novel environments or novel objects in the environment. PMID:26633522

  15. Artificially Increased Yolk Hormone Levels and Neophobia in Domestic Chicks

    PubMed Central

    Bertin, Aline; Arnould, Cécile; Moussu, Chantal; Meurisse, Maryse; Constantin, Paul; Leterrier, Christine; Calandreau, Ludovic

    2015-01-01

    In birds there is compelling evidence that the development and expression of behavior is affected by maternal factors, particularly via variation in yolk hormone concentrations of maternal origin. In the present study we tested whether variation in yolk hormone levels lead to variation in the expression of neophobia in young domestic chicks. Understanding how the prenatal environment could predispose chicks to express fear-related behaviors is essential in order to propose preventive actions and improve animal welfare. We simulated the consequences of a maternal stress by experimentally enhancing yolk progesterone, testosterone and estradiol concentrations in hen eggs prior to incubation. The chicks from these hormone-treated eggs (H) and from sham embryos (C) that received the vehicle-only were exposed to novel food, novel object and novel environment tests. H chicks approached a novel object significantly faster and were significantly more active in a novel environment than controls, suggesting less fearfulness. Conversely, no effect of the treatment was found in food neophobia tests. Our study highlights a developmental influence of yolk hormones on a specific aspect of neophobia. The results suggest that increased yolk hormone levels modulate specifically the probability of exploring novel environments or novel objects in the environment. PMID:26633522

  16. Artificially Increased Yolk Hormone Levels and Neophobia in Domestic Chicks.

    PubMed

    Bertin, Aline; Arnould, Cécile; Moussu, Chantal; Meurisse, Maryse; Constantin, Paul; Leterrier, Christine; Calandreau, Ludovic

    2015-11-30

    In birds there is compelling evidence that the development and expression of behavior is affected by maternal factors, particularly via variation in yolk hormone concentrations of maternal origin. In the present study we tested whether variation in yolk hormone levels lead to variation in the expression of neophobia in young domestic chicks. Understanding how the prenatal environment could predispose chicks to express fear-related behaviors is essential in order to propose preventive actions and improve animal welfare. We simulated the consequences of a maternal stress by experimentally enhancing yolk progesterone, testosterone and estradiol concentrations in hen eggs prior to incubation. The chicks from these hormone-treated eggs (H) and from sham embryos (C) that received the vehicle-only were exposed to novel food, novel object and novel environment tests. H chicks approached a novel object significantly faster and were significantly more active in a novel environment than controls, suggesting less fearfulness. Conversely, no effect of the treatment was found in food neophobia tests. Our study highlights a developmental influence of yolk hormones on a specific aspect of neophobia. The results suggest that increased yolk hormone levels modulate specifically the probability of exploring novel environments or novel objects in the environment.

  17. Effect of Increased Water Vapor Levels on TBC Lifetime

    SciTech Connect

    Pint, Bruce A; Garner, George Walter; Lowe, Tracie M; Haynes, James A; Zhang, Ying

    2011-01-01

    To investigate the effect of increased water vapor levels on thermal barrier coating (TBC) lifetime, furnace cycle tests were performed at 1150 C in air with 10 vol.% water vapor (similar to natural gas combustion) and 90 vol.%. Either Pt diffusion or Pt-modified aluminide bond coatings were applied to specimens from the same batch of a commercial second-generation single-crystal superalloy and commercial vapor-deposited yttria-stabilized zirconia (YSZ) top coats were applied. Three coatings of each type were furnace cycled to failure to compare the average lifetimes obtained in dry O{sub 2}, using the same superalloy batch and coating types. Average lifetimes with Pt diffusion coatings were unaffected by the addition of water vapor. In contrast, the average lifetime of Pt-modified aluminide coatings was reduced by more than 50% with 10% water vapor but only slightly reduced by 90% water vapor. Based on roughness measurements from similar specimens without a YSZ coating, the addition of 10% water vapor increased the rate of coating roughening more than 90% water vapor. Qualitatively, the amount of {beta}-phase depletion in the coatings exposed in 10% water vapor did not appear to be accelerated.

  18. Lysyl hydroxylase 2 induces a collagen cross-link switch in tumor stroma.

    PubMed

    Chen, Yulong; Terajima, Masahiko; Yang, Yanan; Sun, Li; Ahn, Young-Ho; Pankova, Daniela; Puperi, Daniel S; Watanabe, Takeshi; Kim, Min P; Blackmon, Shanda H; Rodriguez, Jaime; Liu, Hui; Behrens, Carmen; Wistuba, Ignacio I; Minelli, Rosalba; Scott, Kenneth L; Sanchez-Adams, Johannah; Guilak, Farshid; Pati, Debananda; Thilaganathan, Nishan; Burns, Alan R; Creighton, Chad J; Martinez, Elisabeth D; Zal, Tomasz; Grande-Allen, K Jane; Yamauchi, Mitsuo; Kurie, Jonathan M

    2015-03-01

    Epithelial tumor metastasis is preceded by an accumulation of collagen cross-links that heighten stromal stiffness and stimulate the invasive properties of tumor cells. However, the biochemical nature of collagen cross-links in cancer is still unclear. Here, we postulated that epithelial tumorigenesis is accompanied by changes in the biochemical type of collagen cross-links. Utilizing resected human lung cancer tissues and a p21CIP1/WAF1-deficient, K-rasG12D-expressing murine metastatic lung cancer model, we showed that, relative to normal lung tissues, tumor stroma contains higher levels of hydroxylysine aldehyde-derived collagen cross-links (HLCCs) and lower levels of lysine aldehyde-derived cross-links (LCCs), which are the predominant types of collagen cross-links in skeletal tissues and soft tissues, respectively. Gain- and loss-of-function studies in tumor cells showed that lysyl hydroxylase 2 (LH2), which hydroxylates telopeptidyl lysine residues on collagen, shifted the tumor stroma toward a high-HLCC, low-LCC state, increased tumor stiffness, and enhanced tumor cell invasion and metastasis. Together, our data indicate that LH2 enhances the metastatic properties of tumor cells and functions as a regulatory switch that controls the relative abundance of biochemically distinct types of collagen cross-links in the tumor stroma. PMID:25664850

  19. Lysyl hydroxylase 2 induces a collagen cross-link switch in tumor stroma.

    PubMed

    Chen, Yulong; Terajima, Masahiko; Yang, Yanan; Sun, Li; Ahn, Young-Ho; Pankova, Daniela; Puperi, Daniel S; Watanabe, Takeshi; Kim, Min P; Blackmon, Shanda H; Rodriguez, Jaime; Liu, Hui; Behrens, Carmen; Wistuba, Ignacio I; Minelli, Rosalba; Scott, Kenneth L; Sanchez-Adams, Johannah; Guilak, Farshid; Pati, Debananda; Thilaganathan, Nishan; Burns, Alan R; Creighton, Chad J; Martinez, Elisabeth D; Zal, Tomasz; Grande-Allen, K Jane; Yamauchi, Mitsuo; Kurie, Jonathan M

    2015-03-01

    Epithelial tumor metastasis is preceded by an accumulation of collagen cross-links that heighten stromal stiffness and stimulate the invasive properties of tumor cells. However, the biochemical nature of collagen cross-links in cancer is still unclear. Here, we postulated that epithelial tumorigenesis is accompanied by changes in the biochemical type of collagen cross-links. Utilizing resected human lung cancer tissues and a p21CIP1/WAF1-deficient, K-rasG12D-expressing murine metastatic lung cancer model, we showed that, relative to normal lung tissues, tumor stroma contains higher levels of hydroxylysine aldehyde-derived collagen cross-links (HLCCs) and lower levels of lysine aldehyde-derived cross-links (LCCs), which are the predominant types of collagen cross-links in skeletal tissues and soft tissues, respectively. Gain- and loss-of-function studies in tumor cells showed that lysyl hydroxylase 2 (LH2), which hydroxylates telopeptidyl lysine residues on collagen, shifted the tumor stroma toward a high-HLCC, low-LCC state, increased tumor stiffness, and enhanced tumor cell invasion and metastasis. Together, our data indicate that LH2 enhances the metastatic properties of tumor cells and functions as a regulatory switch that controls the relative abundance of biochemically distinct types of collagen cross-links in the tumor stroma.

  20. Lysyl hydroxylase 2 induces a collagen cross-link switch in tumor stroma

    PubMed Central

    Chen, Yulong; Terajima, Masahiko; Yang, Yanan; Sun, Li; Ahn, Young-Ho; Pankova, Daniela; Puperi, Daniel S.; Watanabe, Takeshi; Kim, Min P.; Blackmon, Shanda H.; Rodriguez, Jaime; Liu, Hui; Behrens, Carmen; Wistuba, Ignacio I.; Minelli, Rosalba; Scott, Kenneth L.; Sanchez-Adams, Johannah; Guilak, Farshid; Pati, Debananda; Thilaganathan, Nishan; Burns, Alan R.; Creighton, Chad J.; Martinez, Elisabeth D.; Zal, Tomasz; Grande-Allen, K. Jane; Yamauchi, Mitsuo; Kurie, Jonathan M.

    2015-01-01

    Epithelial tumor metastasis is preceded by an accumulation of collagen cross-links that heighten stromal stiffness and stimulate the invasive properties of tumor cells. However, the biochemical nature of collagen cross-links in cancer is still unclear. Here, we postulated that epithelial tumorigenesis is accompanied by changes in the biochemical type of collagen cross-links. Utilizing resected human lung cancer tissues and a p21CIP1/WAF1-deficient, K-rasG12D-expressing murine metastatic lung cancer model, we showed that, relative to normal lung tissues, tumor stroma contains higher levels of hydroxylysine aldehyde–derived collagen cross-links (HLCCs) and lower levels of lysine aldehyde–derived cross-links (LCCs), which are the predominant types of collagen cross-links in skeletal tissues and soft tissues, respectively. Gain- and loss-of-function studies in tumor cells showed that lysyl hydroxylase 2 (LH2), which hydroxylates telopeptidyl lysine residues on collagen, shifted the tumor stroma toward a high-HLCC, low-LCC state, increased tumor stiffness, and enhanced tumor cell invasion and metastasis. Together, our data indicate that LH2 enhances the metastatic properties of tumor cells and functions as a regulatory switch that controls the relative abundance of biochemically distinct types of collagen cross-links in the tumor stroma. PMID:25664850

  1. Relationship between cross-linking conditions of ethylene vinyl acetate and potential induced degradation for crystalline silicon photovoltaic modules

    NASA Astrophysics Data System (ADS)

    Jonai, Sachiko; Hara, Kohjiro; Tsutsui, Yuji; Nakahama, Hidenari; Masuda, Atsushi

    2015-08-01

    In this study, we investigated the relationship in crystalline silicon (c-Si) photovoltaic (PV) modules between the cross-linking level of copolymer of ethylene and vinyl acetate (EVA) as the encapsulant and the degree of degradation due to potential induced degradation (PID) phenomenon. We used three methods for the determination of cross-linking level of EVA: xylene method, which is one of the solvent extraction methods (SEM), curing degree by differential scanning calorimetry (DSC), and viscoelastic properties by dynamic mechanical analysis (DMA). The results indicate that degradation of PV modules by PID test depends on the cross-linking level of EVA. The PV modules encapsulated by EVA with higher cross-linking level show lower degradation degree due to PID phenomenon. Also we showed that EVA with higher cross-linking level tended to be higher volume resistivity. This tendency is similar to that for electrical resistance value during the PID test. The PID test was also done by changing thickness of EVA between front cover glass and c-Si with the same cross-linking level. The PV modules encapsulated by thicker EVA between front cover glass and c-Si cell show lower degradation by PID. From these results, the PV modules encapsulated by EVA with higher cross-linking level, higher volume resistivity and increased thickness would be tolerant of PID phenomenon.

  2. Increased levels of inosine in a mouse model of inflammation

    PubMed Central

    Prestwich, Erin G; Mangerich, Aswin; Pang, Bo; McFaline, Jose L; Lonkar, Pallavi; Sullivan, Matthew R; Trudel, Laura J; Taghizedeh, Koli; Dedon, Peter C

    2013-01-01

    One possible mechanism linking inflammation with cancer involves the generation of reactive oxygen, nitrogen and halogen species by activated macrophages and neutrophils infiltrating sites of infection or tissue damage, with these chemical mediators causing damage that ultimately leads to cell death and mutation. To determine the most biologically deleterious chemistries of inflammation, we previously assessed products across the spectrum of DNA damage arising in inflamed tissues in the SJL mouse model nitric oxide over-production (Pang et al., Carcinogenesis 28: 1807–1813, 2007). Among the anticipated DNA damage chemistries, we observed significant changes only in lipid peroxidation-derived etheno adducts. We have now developed an isotope-dilution, liquid chromatography-coupled, tandem quadrupole mass spectrometric method to quantify representative species across the spectrum of RNA damage products predicted to arise at sites of inflammation, including nucleobase deamination (xanthosine, inosine), oxidation (8-oxoguanosine), and alkylation (1,N6-etheno-adenosine). Application of the method to liver, spleen, and kidney from the SJL mouse model revealed generally higher levels of oxidative background RNA damage than was observed in DNA in control mice. However, compared to control mice, RcsX treatment to induce nitric oxide overproduction resulted in significant increases only in inosine and only in the spleen. Further, the nitric oxide synthase inhibitor, N-methylarginine, did not significantly affect the levels of inosine in control and RcsX-treated mice. The differences between DNA and RNA damage in the same animal model of inflammation point to possible influences from DNA repair, RcsX-induced alterations in adenosine deaminase activity, and differential accessibility of DNA and RNA to reactive oxygen and nitrogen species as determinants of nucleic acid damage during inflammation. PMID:23506120

  3. Cross-linked biopolymer bundles: Cross-link reversibility leads to cooperative binding/unbinding phenomena

    NASA Astrophysics Data System (ADS)

    Vink, Richard L. C.; Heussinger, Claus

    2012-01-01

    We consider a biopolymer bundle consisting of filaments that are cross-linked together. The cross-links are reversible: they can dynamically bind and unbind adjacent filament pairs as controlled by a binding enthalpy. The bundle is subjected to a bending deformation and the corresponding distribution of cross-links is measured. For a bundle consisting of two filaments, upon increasing the bending amplitude, a first-order transition is observed. The transition is from a state where the filaments are tightly coupled by many bound cross-links, to a state of nearly independent filaments with only a few bound cross-links. For a bundle consisting of more than two filaments, a series of first-order transitions is observed. The transitions are connected with the formation of an interface between regions of low and high cross-link densities. Combining umbrella sampling Monte Carlo simulations with analytical calculations, we present a detailed picture of how the competition between cross-link shearing and filament stretching drives the transitions. We also find that, when the cross-links become soft, collective behavior is not observed: the cross-links then unbind one after the other leading to a smooth decrease of the average cross-link density.

  4. Increase in voice level and speaker comfort in lecture rooms.

    PubMed

    Brunskog, Jonas; Gade, Anders Christian; Bellester, Gaspar Payá; Calbo, Lilian Reig

    2009-04-01

    Teachers often suffer from health problems related to their voice. These problems are related to their working environment, including the acoustics of the lecture rooms. However, there is a lack of studies linking the room acoustic parameters to the voice produced by the speaker. In this pilot study, the main goals are to investigate whether objectively measurable parameters of the rooms can be related to an increase in the voice sound power produced by speakers and to the speakers' subjective judgments about the rooms. In six different rooms with different sizes, reverberation times, and other physical attributes, the sound power level produced by six speakers was measured. Objective room acoustic parameters were measured in the same rooms, including reverberation time and room gain, and questionnaires were handed out to people who had experience talking in the rooms. It is found that in different rooms significant changes in the sound power produced by the speaker can be found. It is also found that these changes mainly have to do with the size of the room and to the gain produced by the room. To describe this quality, a new room acoustic quantity called "room gain" is proposed.

  5. Computational exploration of polymer nanocomposite mechanical property modification via cross-linking topology

    SciTech Connect

    Lacevic, N; Gee, R; Saab, A; Maxwell, R

    2008-04-24

    Molecular dynamics simulations have been performed in order to study the effects of nanoscale filler cross-linking topologies and loading levels on the mechanical properties of a model elastomeric nanocomposite. The model system considered here is constructed from octa-functional polyhedral oligomeric silsesquioxane (POSS) dispersed in a poly(dimethylsiloxane) (PDMS) matrix. Shear moduli, G, have been computed for pure and for filled and unfilled PDMS as a function of cross-linking density, POSS fill loading level, and polymer network topology. The results reported here show that G increases as the cross-linking (covalent bonds formed between the POSS and the PDMS network) density increases. Further, G is found to have a strong dependence on cross-linking topology. The increase in shear modulus, G, for POSS filled PDMS is significantly higher than that for unfilled PDMS cross-linked with standard molecular species, suggesting an enhanced reinforcement mechanism for POSS. In contrast, in blended systems (POSS/PDMS mixture with no cross-linking) G was not observed to significantly increase with POSS loading. Finally, we find intriguing differences in the structural arrangement of bond strains between the cross-linked and the blended systems. In the unfilled PDMS the distribution of highly strained bonds appears to be random, while in the POSS filled system, the strained bonds form a net-like distribution that spans the network. Such a distribution may form a structural network 'holding' the composite together and resulting in increases in G compared to an unfilled, cross-linked system. These results are of importance for engineering of new POSS-based multifunctional materials with tailor-made mechanical properties.

  6. Computational exploration of polymer nanocomposite mechanical property modification via cross-linking topology.

    PubMed

    Lacevic, Naida; Gee, Richard H; Saab, Andrew; Maxwell, Robert

    2008-09-28

    Molecular dynamics simulations have been performed in order to study the effects of nanoscale filler cross-linking topologies and loading levels on the mechanical properties of a model elastomeric nanocomposite. The model system considered here is constructed from octafunctional polyhedral oligomeric silsesquioxane (POSS) dispersed in a poly(dimethylsiloxane) (PDMS) matrix. Shear moduli, G, have been computed for pure and for filled and unfilled PDMS as a function of cross-linking density, POSS fill loading level, and polymer network topology. The results reported here show that G increases as the cross-linking (covalent bonds formed between the POSS and the PDMS network) density increases. Further, G is found to have a strong dependence on cross-linking topology. The increase in shear modulus, G, for POSS filled PDMS is significantly higher than that for unfilled PDMS cross-linked with standard molecular species, suggesting an enhanced reinforcement mechanism for POSS. In contrast, in blended systems (POSS/PDMS mixture with no cross-linking) G was not observed to significantly increase with POSS loading. Finally, we find intriguing differences in the structural arrangement of bond strains between the cross-linked and the blended systems. In the unfilled PDMS the distribution of highly strained bonds appears to be random, while in the POSS filled system, the strained bonds form a netlike distribution that spans the network. Such a distribution may form a structural network "holding" the composite together and resulting in increases in G compared to an unfilled, cross-linked system. These results are of importance for engineering of new POSS-based multifunctional materials with tailor-made mechanical properties. PMID:19045061

  7. IMPROVED PHYSICAL PROPERTIES OF ZEIN USING GLYOXAL AS A CROSSLINKER

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The effect of crosslinkers glyoxal, methylglyoxal and formaldehyde on physical properties of zein films was studied. Crosslinker concentrations varied from 0.3 to 6% by zein weight. Films crosslinked with glyoxal and formaldehyde showed a significant increase in tensile strength under certain pH c...

  8. Estuaries May Face Increased Parasitism as Sea Levels Rise

    NASA Astrophysics Data System (ADS)

    Wendel, JoAnna

    2014-12-01

    Invertebrates in estuaries could be at a greater risk of parasitism as climate change causes sea levels to rise. A new paper published 8 December in Proceedings of the National Academy of Sciences of the United States of America (doi:10.1073/pnas.1416747111) describes how rapid sea level rise in the Holocene affected the population of parasitic flatworms called trematodes.

  9. Increases in choline levels in rat brain elicited by meclofenoxate.

    PubMed

    Wood, P L; Péloquin, A

    1982-04-01

    Meclofenoxate, the p-cholorophenoxyacetic acid ester of deanol, was found to dramatically elevate choline (Ch) levels in the rat CNS. In the hippocampus, this elevation in choline was accompanied by a new elevated steady state level in acetylcholine (ACh). No such coupling was observed in the striatum or parietal cortex. Deanol also elevated choline levels in the CNS but was about half as potent as meclofenoxate; p-chlorophenoxyacetic acid was inactive in this respect. Lesions of striatal neurons with kainic acid and of hippocampal cholinergic nerve endings with surgical section of the fimbria indicated that the changes in choline levels were mainly extraneuronal. In spite of the changes in choline and ACh levels, no consistant alterations in ACh turnover were measured. In summary, meclofenoxate induced dramatic alterations in CNS choline metabolism and may, therefore, be a useful therapeutic tool for potentiating depressed cholinergic neurons.

  10. Radiation crosslinking of polypropylene

    NASA Astrophysics Data System (ADS)

    Sawasaki, T.; Nojiri, A.

    The radiation crosslinking of polypropylene (PP) with several of polyfunctional monomers has been examined. Formerly many kinds of PP crosslinking methods have been reported, but these have some problems, such as limitations on the thickness of sheets and the degradation of the resin caused by irradiation. We have found that the polyfunctional monomers can be classified into three types by the irradiation dose necessary for crosslinking. In particular, we have developed a new crosslinking method using a specific crosslinking coagent having an acryloyloxy group with a very low required irradiation dose. If this type of monomer is used, 0.5 Mrad is enough to saturate the crosslinking, while the other two types require more than 5 Mrad. The degree of crosslinking is estimated by the gel fraction, modulus of the molten sheet and that of degradation by elongation and oxidation induction time. The crosslinked PP obtained by this method has many good properties, such as a high modulus, large elongation, and high heat resistance. This method may be applied in the manufacture of foamy and other heat resistant materials.

  11. THE EFFECTS OF HIGH DOSE IRRADIATION ON THE CROSS-LINKING OF VITAMIN E-BLENDED ULTRAHIGH MOLECULAR WEIGHT POLYETHYLENE

    PubMed Central

    Oral, Ebru; Beckos, Christine Godleski; Malhi, Arnaz S.; Muratoglu, Orhun K.

    2008-01-01

    Vitamin E-stabilized, highly cross-linked ultrahigh molecular weight polyethylene (UHMWPE) is a promising oxidation and wear resistant UHMWPE with improved mechanical strength in comparison with the first generation, irradiated and melted UHMWPE. One approach of incorporating vitamin E in UHMWPE is through blending of vitamin E in UHMWPE powder followed by consolidation and radiation crosslinking. However radiation crosslinking efficiency of UHMWPE decreases in the presence of vitamin E. Therefore an optimum vitamin E concentration and radiation dose level needs to be determined to achieve a cross-link density comparable to 100-kGy irradiated and melted UHMWPE, which has shown excellent wear properties in vivo. We investigated the cross-link density and mechanical properties of vitamin E-blended UHMWPEs as a function of vitamin E concentration in the blend and gamma irradiation doses up to 200 kGy. We found that 0.3 wt% vitamin E-blended UHMWPE could not be cross-linked above a cross-link density achieved at a radiation dose of 65 kGy for virgin UHMWPE and 1.0 wt% vitamin E-blended UHMWPE could not be cross-linked above a cross-link density achieved at a radiation dose of 25 kGy for virgin UHMWPE even when the former were irradiated to a radiation dose of 200 kGy. In addition, higher plasticity at vitamin E concentrations at and above 0.3 wt% indicated that increased chain scissioning may be prevalent. Since the wear resistance of this irradiated UHMWPE would be expected to be low, vitamin E concentrations equal to or above 0.3 wt% are not recommended for subsequent irradiation to achieve a wear resistant cross-linked UHMWPE. The long–term oxidative stability of irradiated blends with low vitamin E concentrations has yet to be studied to determine an optimum between cross-link density and long-term oxidative stability. PMID:18514813

  12. Ocean acidification increases fatty acids levels of larval fish.

    PubMed

    Díaz-Gil, Carlos; Catalán, Ignacio A; Palmer, Miquel; Faulk, Cynthia K; Fuiman, Lee A

    2015-07-01

    Rising levels of anthropogenic carbon dioxide in the atmosphere are acidifying the oceans and producing diverse and important effects on marine ecosystems, including the production of fatty acids (FAs) by primary producers and their transfer through food webs. FAs, particularly essential FAs, are necessary for normal structure and function in animals and influence composition and trophic structure of marine food webs. To test the effect of ocean acidification (OA) on the FA composition of fish, we conducted a replicated experiment in which larvae of the marine fish red drum (Sciaenops ocellatus) were reared under a climate change scenario of elevated CO2 levels (2100 µatm) and under current control levels (400 µatm). We found significantly higher whole-body levels of FAs, including nine of the 11 essential FAs, and altered relative proportions of FAs in the larvae reared under higher levels of CO2. Consequences of this effect of OA could include alterations in performance and survival of fish larvae and transfer of FAs through food webs. PMID:26179801

  13. Ocean acidification increases fatty acids levels of larval fish

    PubMed Central

    Díaz-Gil, Carlos; Catalán, Ignacio A.; Palmer, Miquel; Faulk, Cynthia K.; Fuiman, Lee A.

    2015-01-01

    Rising levels of anthropogenic carbon dioxide in the atmosphere are acidifying the oceans and producing diverse and important effects on marine ecosystems, including the production of fatty acids (FAs) by primary producers and their transfer through food webs. FAs, particularly essential FAs, are necessary for normal structure and function in animals and influence composition and trophic structure of marine food webs. To test the effect of ocean acidification (OA) on the FA composition of fish, we conducted a replicated experiment in which larvae of the marine fish red drum (Sciaenops ocellatus) were reared under a climate change scenario of elevated CO2 levels (2100 µatm) and under current control levels (400 µatm). We found significantly higher whole-body levels of FAs, including nine of the 11 essential FAs, and altered relative proportions of FAs in the larvae reared under higher levels of CO2. Consequences of this effect of OA could include alterations in performance and survival of fish larvae and transfer of FAs through food webs. PMID:26179801

  14. Ocean acidification increases fatty acids levels of larval fish.

    PubMed

    Díaz-Gil, Carlos; Catalán, Ignacio A; Palmer, Miquel; Faulk, Cynthia K; Fuiman, Lee A

    2015-07-01

    Rising levels of anthropogenic carbon dioxide in the atmosphere are acidifying the oceans and producing diverse and important effects on marine ecosystems, including the production of fatty acids (FAs) by primary producers and their transfer through food webs. FAs, particularly essential FAs, are necessary for normal structure and function in animals and influence composition and trophic structure of marine food webs. To test the effect of ocean acidification (OA) on the FA composition of fish, we conducted a replicated experiment in which larvae of the marine fish red drum (Sciaenops ocellatus) were reared under a climate change scenario of elevated CO2 levels (2100 µatm) and under current control levels (400 µatm). We found significantly higher whole-body levels of FAs, including nine of the 11 essential FAs, and altered relative proportions of FAs in the larvae reared under higher levels of CO2. Consequences of this effect of OA could include alterations in performance and survival of fish larvae and transfer of FAs through food webs.

  15. In Vivo Oxidative Stability Changes of Highly Cross-Linked Polyethylene Bearings: An Ex Vivo Investigation.

    PubMed

    Rowell, Shannon L; Reyes, Christopher R; Malchau, Henrik; Muratoglu, Orhun K

    2015-10-01

    The development of highly cross-linked UHMWPEs focused on stabilizing radiation-induced free radicals as the sole precursor to oxidative degradation. However, secondary in vivo oxidation mechanisms have been discovered. After a preliminary post-operative analysis, we subjected highly cross-linked retrievals with 1-4 years in vivo durations and never-implanted controls to accelerated aging to predict the extent to which their oxidative stability was compromised in vivo. Lipid absorption, oxidation, and hydroperoxides were measured using infrared spectroscopy. Gravimetric swelling was used to measure cross-link density. After aging, all retrievals, except vitamin E-stabilized components, regardless of initial lipid levels or oxidation, showed significant oxidative degradation, demonstrated by subsurface oxidative peaks, increased hydroperoxides and decreased cross-link density, compared to their post-operative material properties and never-implanted counterparts, confirming oxidative stability changes.

  16. Essential fructosuria: increased levels of fructose 3-phosphate in erythrocytes.

    PubMed

    Petersen, A; Steinmann, B; Gitzelmann, R

    1992-01-01

    Erythrocytes of 3 adult siblings with essential fructosuria contained 45-200 mumol/l fructose 3-phosphate (Fru-3-P), i.e. 3-15 times the concentration in normal controls. Sorbitol 3-phosphate was also increased, but to a lesser degree. An oral load with 50 g of fructose produced an additional 40 mumol/l increase of erythrocyte Fru-3-P after 5 h. The rate of Fru-3-P formation by red cells in vitro was normal. HbA1 and HbA1c were normal. The suspected pathogenetic role of Fru-3-P in diabetic complications is questioned.

  17. Increase in plasma thrombomodulin level in patients with vibration syndrome.

    PubMed

    Kanazuka, M; Shigekiyo, T; Toibana, N; Saito, S

    1996-04-01

    To determine whether endothelial cells are injured in vibration syndrome, we measured plasma levels of thrombomodulin (TM) in 100 patients with this syndrome using one-step sandwich enzyme immunoassay. Plasma level of TM in patients with vibration syndrome was significantly higher than that in normal control (p < 0.0001). There was no significant difference in the plasma TM level between patients with vibration syndrome and those with collagen disease. Plasma TM concentration in chain-saw operators was significantly higher than that in rock-drill operators (p < 0.05). Plasma TM value did not significantly differ between patients with vibration-induced white finger (VWF) and those without VWF. These results suggest that endothelial injury is present in patients with vibration syndrome, the degree of endothelial injury in patients with vibration syndrome equals that in patients with collagen disease, and the endothelial injury in chain-saw operators is greater than that in rock-drill operators. However, there was no difference in the degree of endothelial injury between patients with VWF and those without VWF.

  18. New in situ crosslinking chemistries for hydrogelation

    NASA Astrophysics Data System (ADS)

    Roberts, Meredith Colleen

    Over the last half century, hydrogels have found immense value as biomaterials in a vast number of biomedical and pharmaceutical applications. One subset of hydrogels receiving increased attention is in situ forming gels. Gelling by either bioresponsive self-assembly or mixing of binary crosslinking systems, these technologies are useful in minimally invasive applications as well as drug delivery systems in which the sol-to-gel transition aids the formulation's performance. Thus far, the field of in situ crosslinking hydrogels has received limited attention in the development of new crosslinking chemistries. Moreover, not only does the chemical nature of the crosslinking moieties allow these systems to perform in situ, but they contribute dramatically to the mechanical properties of the hydrogel networks. For example, reversible crosslinks with finite lifetimes generate dynamic viscoelastic gels with time-dependent properties, whereas irreversible crosslinks form highly elastic networks. The aim of this dissertation is to explore two new covalent chemistries for their ability to crosslink hydrogels in situ under physiological conditions. First, reversible phenylboronate-salicylhydroxamate crosslinking was implemented in a binary, multivalent polymeric system. These gels formed rapidly and generated hydrogel networks with frequency-dependent dynamic rheological properties. Analysis of the composition-structure-property relationships of these hydrogels---specifically considering the effects of pH, degree of polymer functionality, charge of the polymer backbone and polymer concentration on dynamic theological properties---was performed. These gels demonstrate diverse mechanical properties, due to adjustments in the binding equilibrium of the pH-sensitive crosslinks, and thus have the potential to perform in a range of dynamic or bioresponsive applications. Second, irreversible catalyst-free "click" chemistry was employed in the hydrogelation of multivalent azide

  19. Corneal Collagen Cross-Linking

    PubMed Central

    Jankov II, Mirko R.; Jovanovic, Vesna; Nikolic, Ljubisa; Lake, Jonathan C.; Kymionis, Georgos; Coskunseven, Efekan

    2010-01-01

    Corneal collagen cross-linking (CXL) with riboflavin and ultraviolet-A (UVA) is a new technique of corneal tissue strengthening by using riboflavin as a photosensitizer and UVA to increase the formation of intra and interfibrillar covalent bonds by photosensitized oxidation. Keratocyte apoptosis in the anterior segment of the corneal stroma all the way down to a depth of about 300 microns has been described and a demarcation line between the treated and untreated cornea has been clearly shown. It is important to ensure that the cytotoxic threshold for the endothelium has not been exceeded by strictly respecting the minimal corneal thickness. Confocal microscopy studies show that repopulation of keratocytes is already visible 1 month after the treatment, reaching its pre-operative quantity and quality in terms of functional morphology within 6 months after the treatment. The major indication for the use of CXL is to inhibit the progression of corneal ectasias, such as keratoconus and pellucid marginal degeneration. CXL may also be effective in the treatment and prophylaxis of iatrogenic keratectasia, resulting from excessively aggressive photoablation. This treatment has also been used to treat infectious corneal ulcers with apparent favorable results. Combination with other treatments, such as intracorneal ring segment implantation, limited topography-guided photoablation and conductive keratoplasty have been used with different levels of success. PMID:20543933

  20. Brassinosteroid Levels Increase Drastically Prior to Morphogenesis of Tracheary Elements

    PubMed Central

    Yamamoto, Ryo; Fujioka, Shozo; Demura, Taku; Takatsuto, Suguru; Yoshida, Shigeo; Fukuda, Hiroo

    2001-01-01

    As the first step toward understanding the involvement of endogenous brassinosteroids (BRs) in cytodifferentiation, we analyzed biosynthetic activities of BRs in zinnia (Zinnia elegans L. cv Canary Bird) cells differentiating into tracheary elements. The results of feeding experiments suggested that both the early and late C6-oxidation pathways occur during tracheary element differentiation. Gas chromatography-mass spectrometry analysis revealed that five BRs, castasterone, typhasterol, 6-deoxocastasterone, 6-deoxotyphasterol, and 6-deoxoteasterone, actually existed in cultured zinnia cells and culture medium. Quantification of endogenous BRs in each stage of tracheary element differentiation by gas chromatography-mass spectrometry exhibited that they increased dramatically prior to the morphogenesis, which was consistent with the idea that BRs are necessary for the initiation of the final stage of tracheary element differentiation. Moreover, the proportion of each BR in culture medium was quite different from that in cells, suggesting that specific BRs are selectively secreted into medium and may function outside the cells. PMID:11161013

  1. Increase of inherent protection level in spent nuclear fuel

    SciTech Connect

    Krasnobaev, A.; Kryuchkov, E.; Glebov, V.

    2006-07-01

    The paper is devoted to upgrading inherent proliferation protection of fissionable nuclear materials (FNM). Some possibilities were investigated to form high radiation barrier inside spent fuel assemblies (SFA) discharged from power reactors of VVER-1000 type and research reactors of IRT type. The radiation barrier is estimated in the terms of rate of equivalent dose (RED) at 30-cm distance from SFA. The values of RED were calculated with application of the computer code package SCALE 4.3. The paper considers the criteria adopted for estimation of FNM proliferation resistance. The paper presents numerical results on a component-wise analysis of the radiation barrier in SFA from reactors of VVER-1000 and IRT type and on capability of various radionuclides to prolong action of the radiation barrier. Isotopic admixtures were selected and amounts of these admixtures were evaluated for significant prolongation of the radiation barrier action at the levels of the radiation standards used for estimation of FNM proliferation resistance. The paper considers vulnerability of the radiation barriers in respect to thermal processing of spent fuel. (authors)

  2. Grafting functional antioxidants on highly crosslinked polyethylene

    NASA Astrophysics Data System (ADS)

    Al-Malaika, S.; Riasat, S.; Lewucha, C.

    2016-05-01

    The problem of interference of antioxidants, such as hindered phenols, with peroxide-initiated crosslinking of polyethylene was addressed through the use of functional (reactive) graftable antioxidants (g-AO). Reactive derivatives of hindered phenol and hindered amine antioxidants were synthesised, characterised and used to investigate their grafting reactions in high density polyethylene; both non-crosslinked (PE) and highly peroxide-crosslinked (PEXa). Assessment of the extent of in-situ grafting of the antioxidants, their retention after exhaustive solvent extraction in PE and PEXa, and the stabilising performance of the grafted antioxidants (g-AO) in the polymer were examined and benchmarked against conventionally stabilised crosslinked & non-crosslinked polyethylene. It was shown that the functional antioxidants graft to a high extent in PEXa, and that the level of interference of the g-AOs with the polymer crosslinking process was minimal compared to that of conventional antioxidants which bear the same antioxidant function. The much higher level of retention of the g-AOs in PEXa after exhaustive solvent extraction, compared to that of the corresponding conventional antioxidants, accounts for their superior long-term thermal stabilising performance under severe extractive conditions.

  3. Disorder by Random Crosslinking in Smectic Elastomers

    NASA Astrophysics Data System (ADS)

    Lambreva, Denitza M.; Ostrovskii, Boris I.; Finkelmann, Heino; de Jeu, Wim H.

    2004-10-01

    We present a high-resolution x-ray study of the effects of disorder due to random crosslinking on the one-dimensional translational ordering in smectic elastomers. At a small crosslink density of about 5%, the elastomer network stabilizes the smectic structure against layer-displacement fluctuations, and the algebraically decaying layer ordering extends up to several micrometers. With increasing concentration of crosslinks, the finite size of these domains is strongly reduced, indicating that disordering takes over. Finally, at a crosslink concentration of 20%, the structure factor can be described by a Lorentzian, which signals extended short-range correlations. The findings are discussed in terms of recent theories of randomly quenched disorder.

  4. Decreased drug accumulation and increased tolerance to DNA damage in tumor cells with a low level of cisplatin resistance.

    PubMed

    Lanzi, C; Perego, P; Supino, R; Romanelli, S; Pensa, T; Carenini, N; Viano, I; Colangelo, D; Leone, R; Apostoli, P; Cassinelli, G; Gambetta, R A; Zunino, F

    1998-04-15

    In an attempt to examine the cellular changes associated with cisplatin resistance, we selected a cisplatin-resistant (A43 1/Pt) human cervix squamous cell carcinoma cell line following continuous in vitro drug exposure. The resistant subline was characterized by a 2.5-fold degree of resistance. In particular, we investigated the expression of cellular defence systems and other cellular factors probably involved in dealing with cisplatin-induced DNA damage. Resistant cells exhibited decreased platinum accumulation and reduced levels of DNA-bound platinum and interstrand cross-link frequency after short-term drug exposure. Analysis of the effect of cisplatin on cell cycle progression revealed a cisplatin-induced G2M arrest in sensitive and resistant cells. Interestingly, a slowdown in S-phase transit was found in A431/Pt cells. A comparison of the ability of sensitive and resistant cells to repair drug-induced DNA damage suggested that resistant cells were able to tolerate higher levels of cisplatin-induced DNA damage than their parental counterparts. Analysis of the expression of proteins involved in DNA mismatch repair showed a decreased level of MSH2 in resistant cells. Since MSH2 seems to be involved in recognition of drug-induced DNA damage, this change may account for the increased tolerance to DNA damage observed in the resistant subline. In conclusion, the involvement of accumulation defects and the increased tolerance to cisplatin-induced DNA damage in these cisplatin-resistant cells support the notion that multiple changes contribute to confer a low level of cisplatin resistance. PMID:9719480

  5. CHARACTERIZATION OF CASEINS CROSSLINKED BY A NATURALLY OCCURRING CROSSLINKING AGENT-GENIPIN

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Increasing economic and environmental pressures demand more effective utilization of natural resources. Genipin, a naturally occurring crosslinking agent obtained from the fruit of Gardenia jasminoides, has recently attracted much attention due to its low cytotoxicity compared to traditional crossli...

  6. Crosslinked, porous, polyacrylate beads

    NASA Technical Reports Server (NTRS)

    Rembaum, Alan (Inventor); Yen, Shiao-Ping S. (Inventor); Dreyer, William J. (Inventor)

    1977-01-01

    Uniformly-shaped, porous, round beads are prepared by the co-polymerization of an acrylic monomer and a cross-linking agent in the presence of 0.05 to 5% by weight of an aqueous soluble polymer such as polyethylene oxide. Cross-linking proceeds at high temperature above about 50.degree. C or at a lower temperature with irradiation. Beads of even shape and even size distribution of less than 2 micron diameter are formed. The beads will find use as adsorbents in chromatography and as markers for studies of cell surface receptors.

  7. Crosslinked, porous, polyacrylate beads

    NASA Technical Reports Server (NTRS)

    Rembaum, Alan (Inventor); Yen, Shiao-Ping Siao (Inventor); Dreyer, William J. (Inventor)

    1976-01-01

    Uniformly-shaped, porous, round beads are prepared by the co-polymerization of an acrylic monomer and a cross-linking agent in the presence of 0.05 to 5% by weight of an aqueous soluble polymer such as polyethylene oxide. Cross-linking proceeds at high temperature above about 50.degree.C or at a lower temperature with irradiation. Beads of even shape and even size distribution of less than 2 micron diameter are formed. The beads will find use as adsorbents in chromatography and as markers for studies of cell surface receptors.

  8. The Effect of Substrate Stiffness, Thickness, and Cross-Linking Density on Osteogenic Cell Behavior

    PubMed Central

    Mullen, Conleth A.; Vaughan, Ted J.; Billiar, Kristen L.; McNamara, Laoise M.

    2015-01-01

    Osteogenic cells respond to mechanical changes in their environment by altering their spread area, morphology, and gene expression profile. In particular, the bulk modulus of the substrate, as well as its microstructure and thickness, can substantially alter the local stiffness experienced by the cell. Although bone tissue regeneration strategies involve culture of bone cells on various biomaterial scaffolds, which are often cross-linked to enhance their physical integrity, it is difficult to ascertain and compare the local stiffness experienced by cells cultured on different biomaterials. In this study, we seek to characterize the local stiffness at the cellular level for MC3T3-E1 cells plated on biomaterial substrates of varying modulus, thickness, and cross-linking concentration. Cells were cultured on flat and wedge-shaped gels made from polyacrylamide or cross-linked collagen. The cross-linking density of the collagen gels was varied to investigate the effect of fiber cross-linking in conjunction with substrate thickness. Cell spread area was used as a measure of osteogenic differentiation. Finite element simulations were used to examine the effects of fiber cross-linking and substrate thickness on the resistance of the gel to cellular forces, corresponding to the equivalent shear stiffness for the gel structure in the region directly surrounding the cell. The results of this study show that MC3T3 cells cultured on a soft fibrous substrate attain the same spread cell area as those cultured on a much higher modulus, but nonfibrous substrate. Finite element simulations predict that a dramatic increase in the equivalent shear stiffness of fibrous collagen gels occurs as cross-linking density is increased, with equivalent stiffness also increasing as gel thickness is decreased. These results provide an insight into the response of osteogenic cells to individual substrate parameters and have the potential to inform future bone tissue regeneration strategies that

  9. The effect of cross-link distributions in axially-ordered, cross-linked networks

    PubMed Central

    Bennett, C. Brad; Kruczek, James; Rabson, D. A.; Matthews, W. Garrett; Pandit, Sagar A.

    2013-01-01

    Cross-linking between the constituent chains of biopolymers has a marked effect on their materials properties. In certain of these materials, such as fibrillar collagen, increases in cross-linking lead to an increase in the melting temperature. Fibrillar collagen is an axially-ordered network of cross-linked polymer chains exhibiting a broadened denaturation transition, which has been explained in terms of the successive denaturation with temperature of multiple species. We model axially-ordered cross-linked materials as stiff chains with distinct arrangements of cross-link-forming sites. Simulations suggest that systems composed of chains with identical arrangements of cross-link-forming sites exhibit critical behavior. In contrast, systems composed of non-identical chains undergo a crossover. This model suggests that the arrangement of cross-link-forming sites may contribute to the broadening of the denaturation transition in fibrillar collagen. PMID:23751928

  10. Playground Designs to Increase Physical Activity Levels during School Recess: A Systematic Review

    ERIC Educational Resources Information Center

    Escalante, Yolanda; García-Hermoso, Antonio; Backx, Karianne; Saavedra, Jose M.

    2014-01-01

    School recess provides a major opportunity to increase children's physical activity levels. Various studies have described strategies to increase levels of physical activity. The purpose of this systematic review is therefore to examine the interventions proposed as forms of increasing children's physical activity levels during recess. A…

  11. Microbes encapsulated within crosslinkable polymers

    DOEpatents

    Chidambaram, Devicharan; Liu, Ying; Rafailovich, Miriam H

    2013-02-05

    The invention relates to porous films comprising crosslinked electrospun hydrogel fibers. Viable microbes are encapsulated within the crosslinked electrospun hydrogel fibers. The crosslinked electrospun hydrogel fibers are water insoluble and permeable. The invention also relates to methods of making and using such porous films.

  12. Riboflavin-induced photo-crosslinking of collagen hydrogel and its application in meniscus tissue engineering.

    PubMed

    Heo, Jiseung; Koh, Rachel H; Shim, Whuisu; Kim, Hwan D; Yim, Hyun-Gu; Hwang, Nathaniel S

    2016-04-01

    A meniscus tear is a common knee injury, but its regeneration remains a clinical challenge. Recently, collagen-based scaffolds have been applied in meniscus tissue engineering. Despite its prevalence, application of natural collagen scaffold in clinical setting is limited due to its extremely low stiffness and rapid degradation. The purpose of the present study was to increase the mechanical properties and delay degradation rate of a collagen-based scaffold by photo-crosslinking using riboflavin (RF) and UV exposure. RF is a biocompatible vitamin B2 that showed minimal cytotoxicity compared to conventionally utilized photo-initiator. Furthermore, collagen photo-crosslinking with RF improved mechanical properties and delayed enzyme-triggered degradation of collagen scaffolds. RF-induced photo-crosslinked collagen scaffolds encapsulated with fibrochondrocytes resulted in reduced scaffold contraction and enhanced gene expression levels for the collagen II and aggrecan. Additionally, hyaluronic acid (HA) incorporation into photo-crosslinked collagen scaffold showed an increase in its retention. Based on these results, we demonstrate that photo-crosslinked collagen-HA hydrogels can be potentially applied in the scaffold-based meniscus tissue engineering.

  13. Chitosan membranes for tissue engineering: comparison of different crosslinkers.

    PubMed

    Ruini, F; Tonda-Turo, C; Chiono, V; Ciardelli, G

    2015-11-03

    Chitosan (CS), a derivative of the naturally occurring biopolymer chitin, is an attractive material for biomedical applications thanks to its biocompatibility, biodegradability, antibacterial properties and ability to enhance cell adhesion and growth compared to other biopolymers. However, the physical and mechanical stability of CS based materials in aqueous solutions is limited and crosslinking agents are required to increase CS performances in a biological environment. In this work, the effect of three highly-biocompatible crosslinkers as genipin (GP), γ-glycidoxypropyltrimethoxysilane (GPTMS), dibasic sodium phosphate (DSP) and a combination of GPTMS and DSP (GPTMS_DSP) on CS physicochemical, thermal, morphological, mechanical properties, swelling and degradation behavior was investigated. Infrared spectroscopy and thermogravimetric analyses confirmed the chemical reaction between CS and the different crosslinkers. CS wettability was enhanced when CS was DSP ionically crosslinked showing contact angle values of about 65° and exhibiting a higher swelling behavior compared to covalently crosslinked films. Moreover, all the crosslinking methods analyzed improved the stability of CS in aqueous media, showed model molecule permeation in time and increased the mechanical properties when compared with non-crosslinked films. The possibility to tailor the final properties of CS scaffolds through crosslinking is a key strategy in applying CS in different biomedical and tissue engineering applications. The obtained results reveal that the optimization of the crosslinking mechanism provides CS membrane properties required in different biomedical applications.

  14. Cross-linked Compared with Historical Polyethylene in THA: An 8-year Clinical Study

    PubMed Central

    Grimm, Bernd; Vencken, Wendy; Heyligers, Ide C.; Tonino, Alphons J.

    2008-01-01

    Wear particle-induced osteolysis is a major cause of aseptic loosening in THA. Increasing wear resistance of polyethylene (PE) occurs by increasing the cross-link density and early reports document low wear rates with such implants. To confirm longer-term reductions in wear we compared cross-linked polyethylene (irradiation in nitrogen, annealing) with historical polyethylene (irradiation in air) in a prospective, randomized clinical study involving 48 patients who underwent THAs with a minimum followup of 7 years (mean, 8 years; range, 7–9 years). The insert material was the only variable. The Harris hip score, radiographic signs of osteolysis, and polyethylene wear were recorded annually. Twenty-three historical and 17 moderately cross-linked polyethylene inserts were analyzed (five patients died, three were lost to followup). At 8 years, the wear rate was lower for cross-linked polyethylene (0.088 ± 0.03 mm/year) than for the historical polyethylene (0.142 ± 0.07 mm/year). This reduction (38%) did not diminish with time (33% at 5 years). Acetabular cyst formation was less frequent (39% versus 12%), affected fewer DeLee and Charnley zones (17% versus 4%), and was less severe for the cross-linked polyethylene. The only revision was for an aseptically loose cup in the historical polyethylene group. Moderately cross-linked polyethylene maintained its wear advantage with time and produced less osteolysis, showing no signs of aging at mid-term followup. Level of Evidence: Level I, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence. PMID:19030941

  15. CO2/light gas separation performance of cross-linked poly(vinylimidazolium) gel membranes as a function of ionic liquid loading and cross-linker content

    SciTech Connect

    Carlisle, TK; Nicodemus, GD; Gin, DL; Noble, RD

    2012-04-15

    A series of cross-linked poly(vinylimidazolium)-RTIL gel membranes was synthesized and evaluated for room-temperature, ideal CO2/N-2, CO2/CH4, and CO2/H-2 separation performance. The membranes were formed by photo-polymerization of oligo(ethylene glycol)-functionalized cross-linking (i.e., di-functional) and non-cross-linking (i.e., mono-functional) vinylimidazolium RTIL monomers with nonpolymerizable, "free RTIL." The effect of free RTIL ([emim][Tf2N]) loading on CO2 separation performance was evaluated by varying RTIL loading at three levels (45, 65, and 75 wt.%). The effect of cross-linker content on CO2 separation performance was also evaluated by varying the copolymer composition of cross-linked membranes from 5 to 100 mol% di-functional monomer. The substituent on the monofunctional RTIL monomer was also varied to investigate the effect of substituent structure and chemistry on CO2 separation performance. CO2 permeability was dramatically increased with higher loading of free RTIL. Increased RTIL loading had no effect on CO2/N-2 or CO2/CH4 permeability selectivity, but significantly improved CO2/H-2 permeability selectivity. Reducing the cross-linking monomer concentration generally improved CO2 permeability. However, anomalous permeability and selectivity behavior was observed below critical concentrations of cross-linker. The effect of the substituent on the monofunctional monomer on CO2 separation performance was minimal compared to the effects of RTIL loading and copolymer composition. (C) 2012 Elsevier B.V. All rights reserved.

  16. Increased von Willebrand factor levels in patients with systemic lupus erythematosus reflect inflammation rather than increased propensity for platelet activation

    PubMed Central

    Raymond, Warren D; Eilertsen, Gro Østli

    2016-01-01

    Background von Willebrand factor (VWF) is involved in platelet plug formation and protein transport. Increased VWF levels in systemic lupus erythematous (SLE) are considered risk factors for vascular events. VWF protein levels, however, do not accurately reflect its platelet-aggregating function, which has not been examined in SLE. Methods Cross-sectional study with clinical and laboratory data obtained in patients with SLE (n=92) from a regional lupus registry. VWF function was determined by ristocetin-induced platelet aggregation (VWF ristocetin cofactor, VWF:RCo) and VWF levels by turbidimetric assay (VWF antigen, VWF:Ag). The platelet-aggregating activity per VWF unit was estimated by the VWF RCo/Ag ratio. Healthy controls served as comparators and associations were evaluated by non-parametric methods. Results VWF:Ag (142% vs 107%, p=0.001) and VWF:RCo levels (123% vs 78%, p<0.041) were increased in patients with SLE, but VWF RCo/Ag ratio was similar as in controls (0.83 vs 0.82, p=0.8). VWF:Ag levels were higher in patients experiencing serositis but unrelated to other manifestations, thrombotic disease, Systemic Lupus Erythematous Disease Activity Index 2000 or Systemic Lupus International Collaborative Clinics-Damage Index. VWF:Ag levels correlated significantly with VWF:RCo levels (Rs 0.8, p<0.001), erythrocyte sedimentation rate (ESR) (Rs 0.32, p<0.01), anti-dsDNA Ab (Rs 0.27, p<0.01), total IgG (Rs 0.33 p<0.01), fibrinogen (Rs 0.28, p<0.01) and ceruloplasmin (Rs 0.367, p<0.01) levels. VWF:RCo levels were not related to clinical findings but were correlated with ESR, anti-dsDNA and transferrin levels. No serological associations existed for VWF RCo/Ag ratio (all p>0.2). Conclusions In this SLE cohort, VWF:Ag behaved similarly to acute-phase reactants, but VWF:Ag increases were not matched by increases in functional activity per unit of VWF. Thus, more VWF did not increase the propensity for platelet aggregation in SLE.

  17. Increased von Willebrand factor levels in patients with systemic lupus erythematosus reflect inflammation rather than increased propensity for platelet activation

    PubMed Central

    Raymond, Warren D; Eilertsen, Gro Østli

    2016-01-01

    Background von Willebrand factor (VWF) is involved in platelet plug formation and protein transport. Increased VWF levels in systemic lupus erythematous (SLE) are considered risk factors for vascular events. VWF protein levels, however, do not accurately reflect its platelet-aggregating function, which has not been examined in SLE. Methods Cross-sectional study with clinical and laboratory data obtained in patients with SLE (n=92) from a regional lupus registry. VWF function was determined by ristocetin-induced platelet aggregation (VWF ristocetin cofactor, VWF:RCo) and VWF levels by turbidimetric assay (VWF antigen, VWF:Ag). The platelet-aggregating activity per VWF unit was estimated by the VWF RCo/Ag ratio. Healthy controls served as comparators and associations were evaluated by non-parametric methods. Results VWF:Ag (142% vs 107%, p=0.001) and VWF:RCo levels (123% vs 78%, p<0.041) were increased in patients with SLE, but VWF RCo/Ag ratio was similar as in controls (0.83 vs 0.82, p=0.8). VWF:Ag levels were higher in patients experiencing serositis but unrelated to other manifestations, thrombotic disease, Systemic Lupus Erythematous Disease Activity Index 2000 or Systemic Lupus International Collaborative Clinics-Damage Index. VWF:Ag levels correlated significantly with VWF:RCo levels (Rs 0.8, p<0.001), erythrocyte sedimentation rate (ESR) (Rs 0.32, p<0.01), anti-dsDNA Ab (Rs 0.27, p<0.01), total IgG (Rs 0.33 p<0.01), fibrinogen (Rs 0.28, p<0.01) and ceruloplasmin (Rs 0.367, p<0.01) levels. VWF:RCo levels were not related to clinical findings but were correlated with ESR, anti-dsDNA and transferrin levels. No serological associations existed for VWF RCo/Ag ratio (all p>0.2). Conclusions In this SLE cohort, VWF:Ag behaved similarly to acute-phase reactants, but VWF:Ag increases were not matched by increases in functional activity per unit of VWF. Thus, more VWF did not increase the propensity for platelet aggregation in SLE. PMID:27651919

  18. Increasing discordant antioxidant protein levels and enzymatic activities contribute to increasing redox imbalance observed during human prostate cancer progression

    PubMed Central

    Chaiswing, Luksana; Zhong, Weixiong; Oberley, Terry D.

    2014-01-01

    A metabolomics study demonstrated a decrease in glutathione and an increase in cysteine (Cys) levels in human prostate cancer (PCa) tissues as Gleason scores increased, indicating redox imbalance with PCa progression. These results were extended in the present study by analyzing redox state of the protein thioredoxin 1 (Trx1) and sulfinylation (SO3) of peroxiredoxins (Prxs) (PrxsSO3) in PCa tissues and cell lines. Lysates of paired human PCa tissues with varying degree of aggressiveness and adjacent benign (BN) tissues were used for analysis. Redox western blot analysis of Trx1 demonstrated low levels of reduced and high levels of oxidized Trx1 (functional and non-functional, respectively) in high grade PCa (Gleason scores 4+4 to 4+5) in comparison to intermediate grade PCa (Gleason scores 3+3 to 3+4) or BN tissues. PrxsSO3 were increased in high grade PCa. Oxidized Trx1 and PrxsSO3 are indicators of oxidative stress. To study whether redox imbalance may potentially affect enzyme activities of antioxidant proteins (AP), we determined levels of selected AP in PCa tissues by western blot analysis and found that mitochondrial manganese superoxide dismutase (MnSOD), Prx 3, and Trx1 were increased in high grade PCa tissues when compared with BN tissues. Enzyme activities of MnSOD in high grade PCa tissues were significantly increased but at a lower magnitude when compared with the levels of MnSOD protein (0.5 folds vs. 2 folds increase). Trx1 activity was not changed in high grade PCa tissues despite a large increase in Trx1 protein expression. Further studies demonstrated a significant increase in posttranslational modifications of tyrosine and lysine residues in MnSOD protein and oxidation of Cys at active site (Cys 32 and Cys 35) and regulatory site (Cys 62 and Cys 69) of Trx1 in high grade PCa compared to BN tissues. These discordant changes between protein levels and enzyme activities are consistent with protein inactivation by redox imbalance and

  19. Crosslinking in viral capsids via tiling theory.

    PubMed

    Twarock, R; Hendrix, R W

    2006-06-01

    A vital part of a virus is its protein shell, called the viral capsid, that encapsulates and hence protects the viral genome. It has been shown in Twarock [2004. A tiling approach to vius capsids assembly explaining a structural puzzle in virology. J. Theor. Biol. 226, 477-482] that the surface structures of viruses with icosahedrally symmetric capsids can be modelled in terms of tilings that encode the locations of the protein subunits. This theory is extended here to multi-level tilings in order to model crosslinking structures. The new framework is demonstrated for the case of bacteriophage HK97, and it is shown, how the theory can be used in general to decide if crosslinking, and what type of crosslinking, is compatible from a mathematical point of view with the geometrical surface structure of a virus.

  20. Photodynamically crosslinked and chitosan-incorporated dentin collagen.

    PubMed

    Shrestha, A; Friedman, S; Kishen, A

    2011-11-01

    A lingering concern with restored root-filled teeth is the loss of structural integrity of the dentin and dentin-sealer interface over time. We hypothesized that crosslinking of dentin collagen with simultaneous incorporation of a biopolymer into collagen matrix would improve its structural stability. This study aimed to investigate the effects of combining chemical/photodynamic crosslinking of dentin collagen with the incorporation of carboxymethyl-chitosan (CMCS) on the resistance to enzymatic degradation and mechanical properties of dentin collagen. Ninety-six demineralized dentin collagen specimens (human, n = 72; and bovine, n = 24) were prepared and crosslinked chemically/ photodynamically, with/without CMCS. Glutaraldehyde and carbodiimides were used for chemical crosslinking, while rose Bengal activated with a non-coherent light (540 nm) at 20 J/cm(2) was applied for photodynamic crosslinking. The crosslinked human dentin collagen was subjected to chemical characterization, 7 days enzymatic degradation, and transmission electron microscopy (TEM), while the bovine dentin collagen was used for tensile-testing. Crosslinked collagen showed significantly higher resistance to enzymatic degradation (p < 0.01), stable ultrastructure, and increased tensile strength (p < 0.05). Crosslinking CMCS with collagen matrix as observed in the TEM further improved the mechanical properties of dentin collagen (p < 0.01). This study highlighted the possibility of improving the resistance and toughness of dentin collagen by chemically/photodynamically crosslinking collagen matrix with CMCS.

  1. Chlorine resistant glutaraldehyde crosslinked polyelectrolyte multilayer membranes for desalination.

    PubMed

    Cho, Kwun Lun; Hill, Anita J; Caruso, Frank; Kentish, Sandra E

    2015-05-01

    Crosslinked polyelectrolyte multilayer membranes are synthesized with salt rejection values approaching those of commercial desalination membranes, but with increased chlorine resistance. The membranes are fabricated directly onto porous commercial substrates. Subsequent crosslinking of the polycation layers with glutaraldehyde leads to NaCl rejections of up to 97%, while the incorporation of a highly sulfonated polysulfone polyanion leads to high chlorine resistance.

  2. Diesterified nitrone rescues nitroso-redox levels and increases myocyte contraction via increased SR Ca(2+) handling.

    PubMed

    Traynham, Christopher J; Roof, Steve R; Wang, Honglan; Prosak, Robert A; Tang, Lifei; Viatchenko-Karpinski, Serge; Ho, Hsiang-Ting; Racoma, Ira O; Catalano, Dominic J; Huang, Xin; Han, Yongbin; Kim, Shang-U; Gyorke, Sandor; Billman, George E; Villamena, Frederick A; Ziolo, Mark T

    2012-01-01

    Nitric oxide (NO) and superoxide (O(2) (-)) are important cardiac signaling molecules that regulate myocyte contraction. For appropriate regulation, NO and O(2) (.-) must exist at defined levels. Unfortunately, the NO and O(2) (.-) levels are altered in many cardiomyopathies (heart failure, ischemia, hypertrophy, etc.) leading to contractile dysfunction and adverse remodeling. Hence, rescuing the nitroso-redox levels is a potential therapeutic strategy. Nitrone spin traps have been shown to scavenge O(2) (.-) while releasing NO as a reaction byproduct; and we synthesized a novel, cell permeable nitrone, 2-2-3,4-dihydro-2H-pyrrole 1-oxide (EMEPO). We hypothesized that EMEPO would improve contractile function in myocytes with altered nitroso-redox levels. Ventricular myocytes were isolated from wildtype (C57Bl/6) and NOS1 knockout (NOS1(-/-)) mice, a known model of NO/O(2) (.-) imbalance, and incubated with EMEPO. EMEPO significantly reduced O(2) (.-) (lucigenin-enhanced chemiluminescence) and elevated NO (DAF-FM diacetate) levels in NOS1(-/-) myocytes. Furthermore, EMEPO increased NOS1(-/-) myocyte basal contraction (Ca(2+) transients, Fluo-4AM; shortening, video-edge detection), the force-frequency response and the contractile response to β-adrenergic stimulation. EMEPO had no effect in wildtype myocytes. EMEPO also increased ryanodine receptor activity (sarcoplasmic reticulum Ca(2+) leak/load relationship) and phospholamban Serine16 phosphorylation (Western blot). We also repeated our functional experiments in a canine post-myocardial infarction model and observed similar results to those seen in NOS1(-/-) myocytes. In conclusion, EMEPO improved contractile function in myocytes experiencing an imbalance of their nitroso-redox levels. The concurrent restoration of NO and O(2) (.-) levels may have therapeutic potential in the treatment of various cardiomyopathies. PMID:23300588

  3. Radiation induced estane polymer crosslinking

    SciTech Connect

    Fletcher, M.; Foster, P.

    1997-12-01

    The exposure of polymeric materials to radiation has been known to induce the effects of crosslinking and degradation. The crosslinking phenomena comes about when two long chain polymers become linked together by a primary bond that extends the chain and increases the viscosity, molecular weight and the elastic modules of the polymer. This process has been observed in relatively short periods of time with fairly high doses of radiation, on the order of several megarads/hour. This paper address low dose exposure over long periods of time to determine what the radiation effects are on the polymeric binder material in PBX 9501. An experimental sample of binder material without explosives will be placed into a thermal and radiation field produced from a W-48 put mod 0. Another sample will be placed in a thermal environment without the radiation. The following is the test plan that was submitted to the Pantex process. The data presented here will be from the first few weeks of exposure and this test will be continued over the next few years. Subsequent data will hopefully be presented in the next compatibility and aging conference.

  4. Physiological response to increasing levels of neurally adjusted ventilatory assist (NAVA).

    PubMed

    Lecomte, François; Brander, Lukas; Jalde, Fredrick; Beck, Jennifer; Qui, Haibo; Elie, Caroline; Slutsky, Arthur S; Brunet, Fabrice; Sinderby, Christer

    2009-04-30

    This study evaluated the response to increasing levels of neurally adjusted ventilatory assist (NAVA), a mode converting electrical activity of the diaphragm (EAdi) into pressure, regulated by a proportionality constant called the NAVA level. Fourteen rabbits were studied during baseline, resistive loading and ramp increases of the NAVA level. EAdi, airway (Paw) and esophageal pressure (Pes), Pes pressure time product (PTPes), breathing pattern, and blood gases were measured. Resistive loading increased PTPes and EAdi. P(a)(CO)(2) increased with high load but not during low load. Increasing NAVA levels increased Paw until a breakpoint where the Paw increase was reduced despite increasing NAVA level. At this breakpoint, Pes, PTPes, EAdi, and P(a)(CO)(2) were similar to baseline. Further increase of the NAVA level reduced Pes, PTPes and EAdi without changes in ventilation. In conclusion, observing the trend in Paw during a ramp increase of the NAVA level allows determination of a level where the inspiratory effort matches unloaded conditions. PMID:19429528

  5. Central injection of CDP-choline suppresses serum ghrelin levels while increasing serum leptin levels in rats.

    PubMed

    Kiyici, Sinem; Basaran, Nesrin Filiz; Cavun, Sinan; Savci, Vahide

    2015-10-01

    In this study we aimed to test central administration of CDP-choline on serum ghrelin, leptin, glucose and corticosterone levels in rats. Intracerebroventricular (i.c.v.) 0.5, 1.0 and 2.0 µmol CDP-choline and saline were administered to male Wistar-Albino rats. For the measurement of serum leptin and ghrelin levels, blood samples were obtained baseline and at 5, 15, 30, 60 and 120 min following i.c.v. CDP-choline injection. Equimolar doses of i.c.v. choline (1.0 µmol) and cytidine (1.0 µmol) were administered and measurements were repeated throughout the second round of the experiment. Atropine (10 µg) and mecamylamine (50 µg) were injected intracerebroventricularly prior to CDP-choline and measurements repeated in the third round of the experiment. After 1 µmol CDP-choline injection, serum ghrelin levels were suppressed significantly at 60 min (P=0.025), whereas serum leptin levels were increased at 60 and 120 min (P=0.012 and P=0.017 respectively). CDP-choline injections also induced a dose- and time-dependent increase in serum glucose and corticosterone levels. The effect of choline on serum leptin and ghrelin levels was similar with CDP-choline while no effect was seen with cytidine. Suppression of serum ghrelin levels was eliminated through mecamylamine pretreatment while a rise in leptin was prevented by both atropine and mecamylamine pretreatments. In conclusion; centrally injected CDP-choline suppressed serum ghrelin levels while increasing serum leptin levels. The observed effects following receptor antagonist treatment suggest that nicotinic receptors play a role in suppression of serum ghrelin levels,whereas nicotinic and muscarinic receptors both play a part in the increase of serum leptin levels.

  6. Fabrication of homobifunctional crosslinker stabilized collagen for biomedical application.

    PubMed

    Lakra, Rachita; Kiran, Manikantan Syamala; Sai, Korrapati Purna

    2015-12-01

    Collagen biopolymer has found widespread application in the field of tissue engineering owing to its excellent tissue compatibility and negligible immunogenicity. Mechanical strength and enzymatic degradation of the collagen necessitates the physical and chemical strength enhancement. One such attempt deals with the understanding of crosslinking behaviour of EGS (ethylene glycol-bis (succinic acid N-hydroxysuccinimide ester)) with collagen to improve the physico-chemical properties. The incorporation of a crosslinker during fibril formation enhanced the thermal and mechanical stability of collagen. EGS crosslinked collagen films exhibited higher denaturation temperature (T d) and the residue left after thermogravimetric analysis was about 16 ± 5.2%. Mechanical properties determined by uniaxial tensile tests showed a threefold increase in tensile strength and Young's modulus at higher concentration (100 μM). Water uptake capacity reduced up to a moderate extent upon crosslinking which is essential for the transport of nutrients to the cells. Cell viability was found to be 100% upon treatment with 100 μM EGS whereas only 30% viability could be observed with glutaraldehyde. Rheological studies of crosslinked collagen showed an increase in shear stress and shear viscosity at 37 °C. Crosslinking with EGS resulted in the formation of a uniform fibrillar network. Trinitrobenzene sulfonate (TNBS) assay confirmed that EGS crosslinked collagen by forming a covalent interaction with ε-amino acids of collagen. The homobifunctional crosslinker used in this study enhanced the effectiveness of collagen as a biomaterial for biomedical application. PMID:26610606

  7. 5 CFR 531.504 - Level of performance required for quality step increase.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... step increase. 531.504 Section 531.504 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS PAY UNDER THE GENERAL SCHEDULE Quality Step Increases § 531.504 Level of performance required for quality step increase. A quality step increase shall not be required but may be granted...

  8. 5 CFR 531.504 - Level of performance required for quality step increase.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... step increase. 531.504 Section 531.504 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS PAY UNDER THE GENERAL SCHEDULE Quality Step Increases § 531.504 Level of performance required for quality step increase. A quality step increase shall not be required but may be granted...

  9. Cold acclimation increases levels of some heat shock protein and sirtuin isoforms in threespine stickleback.

    PubMed

    Teigen, Laura E; Orczewska, Julieanna I; McLaughlin, Jessica; O'Brien, Kristin M

    2015-10-01

    Molecular chaperones [heat shock proteins (HSPs)] increase in response to rapid changes in temperatures, but long-term acclimation to cold temperature may also warrant elevations in HSPs. In fishes, cold acclimation increases mitochondrial density and oxidative stress in some tissues, which may increase demand for HSPs. We hypothesized that levels of HSPs, as well as sirtuins (SIRTs), NAD-dependent deacetylases that mediate changes in metabolism and responses to oxidative stress (including increases in HSPs), would increase during cold acclimation of threespine stickleback (Gasterosteus aculeatus). Transcript levels of hsp70, hsc70, hsp60 and hsp90-α, sirts1-4, as well as protein levels of HSP60, HSP90 and HSC70 were quantified in liver and pectoral adductor muscle of stickleback during cold acclimation from 20 °C to 8 °C. In liver, cold acclimation stimulated a transient increase in mRNA levels of hsp60 and hsc70. Transcript levels of sirt1 and sirt2 also increased in response to cold acclimation and remained elevated. In pectoral muscle, mRNA levels of hsp60, hsp90-α, hsc70 and sirt1 all transiently increased in response to cold acclimation, while levels of sirts2-4 remained constant or declined. Similar to transcript levels, protein levels of HSC70 increased in both liver and pectoral muscle. Levels of HSP90 also increased in liver after 4 weeks at 8 °C. HSP60 remained unchanged in both tissues, as did HSP90 in pectoral muscle. Our results indicate that while both HSPs and SIRTs increase in response to cold acclimation in stickleback, the response is tissue and isoform specific, likely reflecting differences in metabolism and oxidative stress.

  10. Trophic assimilation efficiency markedly increases at higher trophic levels in four-level host-parasitoid food chain.

    PubMed

    Sanders, Dirk; Moser, Andrea; Newton, Jason; van Veen, F J Frank

    2016-03-16

    Trophic assimilation efficiency (conversion of resource biomass into consumer biomass) is thought to be a limiting factor for food chain length in natural communities. In host-parasitoid systems, which account for the majority of terrestrial consumer interactions, a high trophic assimilation efficiency may be expected at higher trophic levels because of the close match of resource composition of host tissue and the consumer's resource requirements, which would allow for longer food chains. We measured efficiency of biomass transfer along an aphid-primary-secondary-tertiary parasitoid food chain and used stable isotope analysis to confirm trophic levels. We show high efficiency in biomass transfer along the food chain. From the third to the fourth trophic level, the proportion of host biomass transferred was 45%, 65% and 73%, respectively, for three secondary parasitoid species. For two parasitoid species that can act at the fourth and fifth trophic levels, we show markedly increased trophic assimilation efficiencies at the higher trophic level, which increased from 45 to 63% and 73 to 93%, respectively. In common with other food chains, δ(15)N increased with trophic level, with trophic discrimination factors (Δ(15)N) 1.34 and 1.49‰ from primary parasitoids to endoparasitic and ectoparasitic secondary parasitoids, respectively, and 0.78‰ from secondary to tertiary parasitoids. Owing to the extraordinarily high efficiency of hyperparasitoids, cryptic higher trophic levels may exist in host-parasitoid communities, which could alter our understanding of the dynamics and drivers of community structure of these important systems.

  11. 12 CFR 263.85 - Establishment of increased capital level for specific institutions.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... establish a capital level higher than the minimum specified in the Board's Capital Adequacy Guidelines for a... capital levels above those in the Board's Capital Adequacy Guidelines may be necessary and appropriate for... 12 Banks and Banking 3 2010-01-01 2010-01-01 false Establishment of increased capital level...

  12. Effects of Collagen Crosslinking on Bone Material Properties in Health and Disease.

    PubMed

    Saito, Mitsuru; Marumo, Keishi

    2015-09-01

    Data have accumulated to show that various types of collagen crosslinking are implicated in the health of individuals, as well as in a number of disease states, such as osteoporosis, diabetes mellitus, chronic kidney disease, inflammatory bowel disease, or in conditions of mild hyperhomocysteinemia, or when glucocorticoid use is indicated. Collagen crosslinking is a posttranslational modification of collagen molecules and plays important roles in tissue differentiation and in the mechanical properties of collagenous tissue. The crosslinking of collagen in the body can form via two mechanisms: one is enzymatic crosslinking and the other is nonenzymatic crosslinking. Lysyl hydroxylases and lysyl oxidases regulate tissue-specific crosslinking patterns and quantities. Enzymatic crosslinks initially form via immature divalent crosslinking, and a portion of them convert into mature trivalent forms such as pyridinoline and pyrrole crosslinks. Nonenzymatic crosslinks form as a result of reactions which create advanced glycation end products (AGEs), such as pentosidine and glucosepane. These types of crosslinks differ in terms of their mechanisms of formation and function. Impaired enzymatic crosslinking and/or an increase of AGEs have been proposed as a major cause of bone fragility associated with aging and numerous disease states. This review focuses on the effects of collagen crosslinking on bone material properties in health and disease.

  13. Spine fusion cross-link causing delayed dural erosion and CSF leak: case report.

    PubMed

    Rahmathulla, Gazanfar; Deen, H Gordon

    2015-04-01

    The past 2 decades have seen a considerable increase in the number of lumbar spinal fusion surgeries. To enhance spinal stabilization and fusion, make the construct resistant to or stiffer for axial stress loading, lateral bending, and torsional stresses, cross-links and connectors were designed and included in a rod-screw construct. The authors present the case of a 49-year-old woman who presented 11 years after undergoing an L4-5 decompression and fusion in which a pedicle screw-rod construct with an integrated cross-link was designed to attach onto the pedicle screws. The patient's response at the time to the initial surgery was excellent; however, at the time of presentation 11 years later, she had significant postural headaches, severe neurogenic claudication, and radiculopathy. Imaging revealed canal compression across the instrumented levels and a possible thickened adherent filum terminale. Reexploration of the level revealed a large erosive dural defect with a CSF leak, spinal canal compression, and a thickened filum at the level of the cross-link. To the author's knowledge, such complications have not been reported in literature. The authors discuss this rare complication of spinal fusion and the need to avoid dural compression when cross-links are used. PMID:25635637

  14. Effect of dual modification with hydroxypropylation and cross-linking on physicochemical properties of taro starch.

    PubMed

    Hazarika, Bidyut Jyoti; Sit, Nandan

    2016-04-20

    Dual modification of taro starch by hydroxypropylation and cross-linking was carried out and the properties of the modified starches were investigated. Two different levels of hydroxypropylation (5 and 10%) and cross-linking (0.05 and 0.10%) were used in different sequences. The amylose contents of the starch decreased due to single and dual modification. For the dual-modified starches, the swelling, solubility and clarity was found to increase with level of hydroxypropylation and decrease with level of cross-linking. The freeze-thaw stability of the dual-modified starches was also affected by the sequence of modification. The viscosities of the cross-linked and dual-modified starches were more than native and hydroxypropylated starches. The firmness of the dual-modified starches was also higher than native and single modified starches. The dual-modified starches have benefits of both type of modifications and could be used for specific purposes e.g. food products requiring high viscosity as well as freeze-thaw stability. PMID:26876854

  15. Effect of dual modification with hydroxypropylation and cross-linking on physicochemical properties of taro starch.

    PubMed

    Hazarika, Bidyut Jyoti; Sit, Nandan

    2016-04-20

    Dual modification of taro starch by hydroxypropylation and cross-linking was carried out and the properties of the modified starches were investigated. Two different levels of hydroxypropylation (5 and 10%) and cross-linking (0.05 and 0.10%) were used in different sequences. The amylose contents of the starch decreased due to single and dual modification. For the dual-modified starches, the swelling, solubility and clarity was found to increase with level of hydroxypropylation and decrease with level of cross-linking. The freeze-thaw stability of the dual-modified starches was also affected by the sequence of modification. The viscosities of the cross-linked and dual-modified starches were more than native and hydroxypropylated starches. The firmness of the dual-modified starches was also higher than native and single modified starches. The dual-modified starches have benefits of both type of modifications and could be used for specific purposes e.g. food products requiring high viscosity as well as freeze-thaw stability.

  16. Possible Increase in Serum FABP4 Level Despite Adiposity Reduction by Canagliflozin, an SGLT2 Inhibitor

    PubMed Central

    Furuhashi, Masato; Matsumoto, Megumi; Hiramitsu, Shinya; Omori, Akina; Tanaka, Marenao; Moniwa, Norihito; Yoshida, Hideaki; Ishii, Junnichi; Miura, Tetsuji

    2016-01-01

    Background Fatty acid-binding protein 4 (FABP4/A-FABP/aP2) is secreted from adipocytes in association with catecholamine-induced lipolysis, and elevated serum FABP4 level is associated with obesity, insulin resistance and atherosclerosis. Secreted FABP4 as a novel adipokine leads to insulin resistance via increased hepatic glucose production (HGP). Sodium-glucose cotransporter 2 (SGLT2) inhibitors decrease blood glucose level via increased urinary glucose excretion, though HGP is enhanced. Here we investigated whether canagliflozin, an SGLT2 inhibitor, modulates serum FABP4 level. Methods Canagliflozin (100 mg/day) was administered to type 2 diabetic patients (n = 39) for 12 weeks. Serum FABP4 level was measured before and after treatment. Results At baseline, serum FABP4 level was correlated with adiposity, renal dysfunction and noradrenaline level. Treatment with canagliflozin significantly decreased adiposity and levels of fasting glucose and HbA1c but increased average serum FABP4 level by 10.3% (18.0 ± 1.0 vs. 19.8 ± 1.2 ng/ml, P = 0.008), though elevation of FABP4 level after treatment was observed in 26 (66.7%) out of 39 patients. Change in FABP4 level was positively correlated with change in levels of fasting glucose (r = 0.329, P = 0.044), HbA1c (r = 0.329, P = 0.044) and noradrenaline (r = 0.329, P = 0.041) but was not significantly correlated with change in adiposity or other variables. Conclusions Canagliflozin paradoxically increases serum FABP4 level in some diabetic patients despite amelioration of glucose metabolism and adiposity reduction, possibly via induction of catecholamine-induced lipolysis in adipocytes. Increased FABP4 level by canagliflozin may undermine the improvement of glucose metabolism and might be a possible mechanism of increased HGP by inhibition of SGLT2. Trial Registration UMIN-CTR Clinical Trial UMIN000018151 PMID:27124282

  17. Effect of O6-methylguanine on DNA interstrand cross-link formation by chloroethylnitrosoureas and 2-chloroethyl(methylsulfonyl)methanesulfonate.

    PubMed

    Dolan, M E; Pegg, A E; Hora, N K; Erickson, L C

    1988-07-01

    Exposure of HT29 cells in culture to O6-methylguanine is known to result in a reduction in O6-alkylguanine-DNA alkyltransferase (AGT) activity and an enhancement of sensitivity to the cytotoxic effects of chloroethylating agents. Since cytotoxicity of these agents may be mediated by the formation of interstrand cross-links, alkaline elution analysis was performed on HT29 cells treated with 1-(2-chloroethyl)-1-nitrosourea, 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea, and Clomesone [2-chloroethyl(methylsulfonyl)methanesulfonate] in the presence or absence of O6-methylguanine pretreatment to determine if the enhanced toxicity was due to an increase in the number of cross-links formed. Interstrand cross-linking by 1-(2-chloroethyl)-1-nitrosourea or 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea was increased by pretreatment with 0.4 mM O6-methylguanine for 24 h. Cross-linking by Clomesone was observed only in cells exposed to 0.4 mM O6-methylguanine for 24 h prior to administration of the drug and for 12 h after administration, suggesting that the resynthesis of the AGT may prevent the cross-linking by Clomesone. Complete recovery of AGT activity after reduction to 20 to 30% of the basal level upon treatment with 0.4 mM O6-methylguanine required between 8 h and 15 h in both HT29 cells and in Raji cells which were also sensitized to 1-(2-chloro-ethyl)-3-cyclohexyl-1-nitrosourea by exposure to O6-methylguanine. These data suggest that the enhancement of chloroethylnitrosourea toxicity after treatment with O6-methylguanine may be related to an increase in the number of DNA cross-links and that the relatively rapid rate of AGT recovery plays a role in prevention of cross-links resulting from Clomesone.

  18. DNA Photolithography with Cinnamate Crosslinkers

    NASA Technical Reports Server (NTRS)

    Feng, Lang (Inventor); Chaikin, Paul Michael (Inventor)

    2016-01-01

    The present invention relates generally to cinnamate crosslinkers. Specifically, the present invention relates to gels, biochips, and functionalized surfaces useful as probes, in assays, in gels, and for drug delivery, and methods of making the same using a newly-discovered crosslinking configuration.

  19. Acute UV irradiation increases heparan sulfate proteoglycan levels in human skin.

    PubMed

    Jung, Ji-Yong; Oh, Jang-Hee; Kim, Yeon Kyung; Shin, Mi Hee; Lee, Dayae; Chung, Jin Ho

    2012-03-01

    Glycosaminoglycans are important structural components in the skin and exist as various proteoglycan forms, except hyaluronic acid. Heparan sulfate (HS), one of the glycosaminoglycans, is composed of repeated disaccharide units, which are glucuronic acids linked to an N-acetyl-glucosamine or its sulfated forms. To investigate acute ultraviolet (UV)-induced changes of HS and HS proteoglycans (HSPGs), changes in levels of HS and several HSPGs in male human buttock skin were examined by immunohistochemistry and real-time quantitative polymerase chain reaction (qPCR) after 2 minimal erythema doses (MED) of UV irradiation (each n = 4-7). HS staining revealed that 2 MED of UV irradiation increased its expression, and staining for perlecan, syndecan-1, syndecan-4, CD44v3, and CD44 showed that UV irradiation increased their protein levels. However, analysis by real-time qPCR showed that UV irradiation did not change mRNA levels of CD44 and agrin, and decreased perlecan and syndecan-4 mRNA levels, while increased syndecan-1 mRNA level. As HS-synthesizing or -degrading enzymes, exostosin-1 and heparanase mRNA levels were increased, but exostosin-2 was decreased by UV irradiation. UV-induced matrix metalloproteinase-1 expression was confirmed for proper experimental conditions. Acute UV irradiation increases HS and HSPG levels in human skin, but their increase may not be mediated through their transcriptional regulation.

  20. Preparation of DNA-crosslinked polyacrylamide hydrogels.

    PubMed

    Previtera, Michelle L; Langrana, Noshir A

    2014-01-01

    Mechanobiology is an emerging scientific area that addresses the critical role of physical cues in directing cell morphology and function. For example, the effect of tissue elasticity on cell function is a major area of mechanobiology research because tissue stiffness modulates with disease, development, and injury. Static tissue-mimicking materials, or materials that cannot alter stiffness once cells are plated, are predominately used to investigate the effects of tissue stiffness on cell functions. While information gathered from static studies is valuable, these studies are not indicative of the dynamic nature of the cellular microenvironment in vivo. To better address the effects of dynamic stiffness on cell function, we developed a DNA-crosslinked polyacrylamide hydrogel system (DNA gels). Unlike other dynamic substrates, DNA gels have the ability to decrease or increase in stiffness after fabrication without stimuli. DNA gels consist of DNA crosslinks that are polymerized into a polyacrylamide backbone. Adding and removing crosslinks via delivery of single-stranded DNA allows temporal, spatial, and reversible control of gel elasticity. We have shown in previous reports that dynamic modulation of DNA gel elasticity influences fibroblast and neuron behavior. In this report and video, we provide a schematic that describes the DNA gel crosslinking mechanisms and step-by-step instructions on the preparation DNA gels. PMID:25226067

  1. Strategies for Mitigating the Reduction in Economic Value of Variable Generation with Increasing Penetration Levels

    SciTech Connect

    Mills, Andrew; Wiser, Ryan

    2014-03-03

    In this report, we evaluate individual options that have the potential to stem the decline in the marginal value of variable generation (VG) with increasing penetration levels. We focus only on the effectiveness of mitigation measures for wind and PV.

  2. Increased levels of adrenocortical and gonadal hormones in mild to moderate Alzheimer's disease.

    PubMed

    Rasmuson, Sigbritt; Näsman, Birgitta; Carlström, Kjell; Olsson, Tommy

    2002-01-01

    Hormonal changes during normal aging include decreasing levels of gonadal hormones and adrenal androgens. These hormones influence multiple nervous functions, including cognition and mood. Related to this, abnormalities at several levels of the hypothalamic-pituitary-adrenal axis (HPA) have been reported in patients with Alzheimer's disease (AD). We studied steroid hormones in 33 patients with mild to moderate AD (12 men; 21 women, 76.4 +/- 7.8 years) and 22 healthy elderly controls (10 men; 12 women, 75.4 +/- 7.5 years old, respectively). Basal levels of serum cortisol, dehydroepiandrosterone (DHEA) and androstenedione were significantly increased in AD patients. Women with AD had significantly higher levels of DHEA and androstenedione. Serum estradiol levels were non-significantly increased in women with AD. After adjustment for age and BMI women with AD had significantly increased levels of androstenedione and DHEA. Increased gonadal hormone levels in mild to moderate AD may reflect an increased secretion, and/or alterations in metabolism of these hormones. This may influence the symptomatology and progression of the disease.

  3. Aerobic conditions increase isoprenoid biosynthesis pathway gene expression levels for carotenoid production in Enterococcus gilvus.

    PubMed

    Hagi, Tatsuro; Kobayashi, Miho; Nomura, Masaru

    2015-06-01

    Some lactic acid bacteria that harbour carotenoid biosynthesis genes (crtNM) can produce carotenoids. Although aerobic conditions can increase carotenoid production and crtNM expression levels, their effects on the pathways that synthesize carotenoid precursors such as mevalonate and isoprene are not completely understood. In this study, we investigated whether aerobic conditions affected gene expression levels involved in the isoprenoid biosynthesis pathway that includes the mevalonate and isoprene biosynthesis pathways in Enterococcus gilvus using real-time quantitative reverse transcription PCR. NADH oxidase (nox) and superoxide dismutase (sod) gene expression levels were investigated as controls for aerobic conditions. The expression levels of nox and sod under aerobic conditions were 7.2- and 8.0-fold higher, respectively, than those under anaerobic conditions. Aerobic conditions concomitantly increased the expression levels of crtNM carotenoid biosynthesis genes. HMG-CoA synthase gene expression levels in the mevalonate pathway were only slightly increased under aerobic conditions, whereas the expression levels of HMG-CoA reductase and five other genes in the isoprene biosynthesis pathways were 1.2-2.3-fold higher than those under anaerobic conditions. These results demonstrated that aerobic conditions could increase the expression levels of genes involved in the isoprenoid biosynthesis pathway via mevalonate in E. gilvus.

  4. Increasing levels of assistance in refinement of knowledge-based retrieval systems

    NASA Technical Reports Server (NTRS)

    Baudin, Catherine; Kedar, Smadar; Pell, Barney

    1994-01-01

    The task of incrementally acquiring and refining the knowledge and algorithms of a knowledge-based system in order to improve its performance over time is discussed. In particular, the design of DE-KART, a tool whose goal is to provide increasing levels of assistance in acquiring and refining indexing and retrieval knowledge for a knowledge-based retrieval system, is presented. DE-KART starts with knowledge that was entered manually, and increases its level of assistance in acquiring and refining that knowledge, both in terms of the increased level of automation in interacting with users, and in terms of the increased generality of the knowledge. DE-KART is at the intersection of machine learning and knowledge acquisition: it is a first step towards a system which moves along a continuum from interactive knowledge acquisition to increasingly automated machine learning as it acquires more knowledge and experience.

  5. Preparation and characterization of IPN hydrogels composed of chitosan and gelatin cross-linked by genipin.

    PubMed

    Cui, Li; Jia, Junfang; Guo, Yi; Liu, Yun; Zhu, Ping

    2014-01-01

    The interpenetrating polymer networks (IPN) hydrogels based on chitosan and gelatin using genipin as the cross-linker were prepared and characterized. The IPN formation of the genipin-cross-linked chitosan/gelatin hydrogel was confirmed by means of the instrinsic viscosity measurement, Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM) and the ninhydrin assays. The instrinsic viscosity measurement, FT-IR and SEM suggested that chitosan and gelatin were miscible in the molecular level. The miscibility leads to the formation of IPN after cross-linking. FT-IR also examined the cross-linking mechanism of genipin with primary amino groups. The degree of cross-linking increased with increase genipin concentration. Swelling results revealed that the IPN hydrogels are pH-sensitive, exhibiting reversibility and rather rapidly response in swelling to pH changes. It is expected this IPN hydrogel has potential as controlled drug delivery system or as alternative sorbents for biomedical and environmental use as pH altered. PMID:24274476

  6. Acute aerobic exercise increases brain-derived neurotrophic factor levels in elderly with Alzheimer's disease.

    PubMed

    Coelho, Flávia Gomes de Melo; Vital, Thays Martins; Stein, Angelica Miki; Arantes, Franciel José; Rueda, André Veloso; Camarini, Rosana; Teodorov, Elizabeth; Santos-Galduróz, Ruth Ferreira

    2014-01-01

    Studies indicate the involvement of brain-derived neurotrophic factor (BDNF) in the pathogenesis of Alzheimer's disease (AD). Decreased BDNF levels may constitute a lack of trophic support and contribute to cognitive impairment in AD. The benefits of acute and chronic physical exercise on BDNF levels are well-documented in humans, however, exercise effects on BDNF levels have not been analyzed in older adults with AD. The aim of this study was to investigate the effects of acute aerobic exercise on BDNF levels in older adults with AD and to verify associations among BDNF levels, aerobic fitness, and level of physical activity. Using a controlled design, twenty-one patients with AD (76.3 ± 6.2 years) and eighteen healthy older adults (74.6 ± 4.7 years) completed an acute aerobic exercise. The outcomes included measures of BDNF plasma levels, aerobic fitness (treadmill grade, time to exhaustion, VO2, and maximal lactate) and level of physical activity (Baecke Questionnaire Modified for the Elderly). The independent t-test shows differences between groups with respect to the BDNF plasma levels at baseline (p = 0.04; t = 4.53; df = 37). In two-way ANOVA, a significant effect of time was found (p = 0.001; F = 13.63; df = 37), the aerobic exercise significantly increased BDNF plasma levels in AD patients and healthy controls. A significant correlation (p = 0.04; r = 0.33) was found between BDNF levels and the level of physical activity. The results of our study suggest that aerobic exercise increases BDNF plasma levels in patients with AD and healthy controls. In addition to that, BDNF levels had association with level of physical activity.

  7. Effectiveness of trimethylopropane trimethacrylate for the electron-beam-irradiation-induced cross-linking of polylactic acid

    NASA Astrophysics Data System (ADS)

    Ng, Hon-Meng; Bee, Soo-Tueen; Ratnam, C. T.; Sin, Lee Tin; Phang, Yee-Yao; Tee, Tiam-Ting; Rahmat, A. R.

    2014-01-01

    The purpose of this research was to investigate the effects of various loading levels of trimethylopropane trimethacrylate (TMPTMA) on the properties of polylactic acid (PLA) cross-linked via electron-beam irradiation. PLA was compounded with 3-5 wt.% of TMPTMA to induce cross-linking upon subjection to electron-beam irradiation doses of 25-250 kGy. The physical properties of the PLA samples were characterised by means of X-ray diffraction, gel fraction and scanning electron microscopy analyses on fractured surfaces after tensile tests. The presence of TMPTMA in PLA was found to effectively increase the crystallite size and gel fraction. However, higher loading levels of TMPTMA could compromise the properties of the PLA/TMPTMA samples, indicating that a larger amount of monomer free radicals might promote degradation within the substantially cross-linked amorphous phase. Irradiation-induced cross-linking in the samples could improve the cross-linking density while decreasing the elongation and interfering with the crystallisation. These effects are caused by the intensive irradiation-induced chain scission that is responsible for the deterioration of the mechanical and crystalline properties of the samples.

  8. Increase in thyroid stimulating hormone levels in patients with gout treated with inhibitors of xanthine oxidoreductase.

    PubMed

    Perez-Ruiz, Fernando; Chinchilla, Sandra Pamela; Atxotegi, Joana; Urionagüena, Irati; Herrero-Beites, Ana Maria; Aniel-Quiroga, Maria Angeles

    2015-11-01

    Increase in thyroid stimulating hormone (TSH) levels over the upper normal limit has been reported in a small percentage of patients treated with febuxostat in clinical trials, but a mechanistic explanation is not yet available. In an observational parallel longitudinal cohort study, we evaluated changes in TSH levels in patients with gout at baseline and during urate-lowering treatment with febuxostat. Patients to be started on allopurinol who had a measurement of TSH in the 6-month period prior to baseline evaluation were used for comparison. TSH levels and change in TSH levels at 12-month follow-up were compared between groups. Patients with abnormal TSH levels or previous thyroid disease or on amiodarone were not included for analysis. Eighty-eight patients treated with febuxostat and 87 with allopurinol were available for comparisons. Patients to be treated with febuxostat had higher urate levels and TSH levels, more severe gout, and poorer renal function, but were similar regarding other characteristics. A similar rise in TSH levels was observed in both groups (0.4 and 0.5 µUI/mL for febuxostat and allopurinol, respectively); at 12-mo, 7/88 (7.9 %) of patients on febuxostat and 4/87 (3.4 %) of patients on allopurinol showed TSH levels over 0.5 µUI/mL. Doses prescribed (corrected for estimated glomerular filtration rate in the case if patients on allopurinol) and baseline TSH levels were determinants of TSH levels at 12-month follow-up. No impact on free T4 (fT4) levels was observed. Febuxostat, but also allopurinol, increased TSH levels in a dose-dependent way, thus suggesting rather a class effect than a drug effect, but with no apparent impact on either clinical or fT4 levels. PMID:26342297

  9. Increase in thyroid stimulating hormone levels in patients with gout treated with inhibitors of xanthine oxidoreductase.

    PubMed

    Perez-Ruiz, Fernando; Chinchilla, Sandra Pamela; Atxotegi, Joana; Urionagüena, Irati; Herrero-Beites, Ana Maria; Aniel-Quiroga, Maria Angeles

    2015-11-01

    Increase in thyroid stimulating hormone (TSH) levels over the upper normal limit has been reported in a small percentage of patients treated with febuxostat in clinical trials, but a mechanistic explanation is not yet available. In an observational parallel longitudinal cohort study, we evaluated changes in TSH levels in patients with gout at baseline and during urate-lowering treatment with febuxostat. Patients to be started on allopurinol who had a measurement of TSH in the 6-month period prior to baseline evaluation were used for comparison. TSH levels and change in TSH levels at 12-month follow-up were compared between groups. Patients with abnormal TSH levels or previous thyroid disease or on amiodarone were not included for analysis. Eighty-eight patients treated with febuxostat and 87 with allopurinol were available for comparisons. Patients to be treated with febuxostat had higher urate levels and TSH levels, more severe gout, and poorer renal function, but were similar regarding other characteristics. A similar rise in TSH levels was observed in both groups (0.4 and 0.5 µUI/mL for febuxostat and allopurinol, respectively); at 12-mo, 7/88 (7.9 %) of patients on febuxostat and 4/87 (3.4 %) of patients on allopurinol showed TSH levels over 0.5 µUI/mL. Doses prescribed (corrected for estimated glomerular filtration rate in the case if patients on allopurinol) and baseline TSH levels were determinants of TSH levels at 12-month follow-up. No impact on free T4 (fT4) levels was observed. Febuxostat, but also allopurinol, increased TSH levels in a dose-dependent way, thus suggesting rather a class effect than a drug effect, but with no apparent impact on either clinical or fT4 levels.

  10. Agomelatine Increases BDNF Serum Levels in Depressed Patients in Correlation with the Improvement of Depressive Symptoms

    PubMed Central

    Pettorruso, Mauro; De Berardis, Domenico; Varasano, Paola Annunziata; Lucidi Pressanti, Gabriella; De Remigis, Valeria; Valchera, Alessandro; Ricci, Valerio; Di Nicola, Marco; Janiri, Luigi; Biggio, Giovanni; Di Giannantonio, Massimo

    2016-01-01

    Background: Agomelatine modulates brain-derived neurotrophic factor expression via its interaction with melatonergic and serotonergic receptors and has shown promising results in terms of brain-derived neurotrophic factor increase in animal models. Methods: Twenty-seven patients were started on agomelatine (25mg/d). Venous blood was collected and brain-derived neurotrophic factor serum levels were measured at baseline and after 2 and 8 weeks along with a clinical assessment, including Hamilton Depression Rating Scale and Snaith-Hamilton Pleasure Scale. Results: Brain-derived neurotrophic factor serum concentration increased after agomelatine treatment. Responders showed a significant increase in brain-derived neurotrophic factor levels after 2 weeks of agomelatine treatment; no difference was observed in nonresponders. Linear regression analysis showed that more prominent brain-derived neurotrophic factor level variation was associated with lower baseline BDNF levels and greater anhedonic features at baseline. Conclusions: Patients affected by depressive disorders showed an increase of brain-derived neurotrophic factor serum concentration after a 2-week treatment with agomelatine. The increase of brain-derived neurotrophic factor levels was found to be greater in patients with lower brain-derived neurotrophic factor levels and marked anhedonia at baseline. PMID:26775293

  11. Increased CD28 serum levels are not associated with specific clinical activity in systemic lupus erythematosus.

    PubMed

    Brambila-Tapia, Aniel J L; Gámez-Nava, Jorge I; Salazar-Páramo, Mario; Munoz-Valle, José F; González-López, Laura; Llamas-Covarrubias, Mara A; Gutiérrez-Urena, Sergio R; Vázquez-Del Mercado, Mónica; Dávalos-Rodríguez, Ingrid P

    2011-10-01

    CD28 is one of the main activator receptors involved in systemic lupus erythematosus (SLE) pathogenesis, and its expression and serum levels are significantly higher in patients with SLE and other autoimmune diseases than in healthy controls (HC). However, it is unknown whether this increase is associated with specific organ damage. Therefore, our objective was to measure the CD28 levels in serum from SLE and HC groups to confirm the CD28 serum levels increase, as reported previously, and to determine whether this increase was associated with specific organ activity and the SLE Disease Activity Index (SLEDAI). Forty SLE patients and 40 matched HC were included, and the age, disease duration, SLEDAI and Mexican SLEDAI were recorded for the SLE group. CD28 serum levels were measured by ELISA. There was a statistically significant increase in the CD28 serum levels of SLE patients compared to controls (p = 0.039); however, we did not find any significant correlation with disease activity indices or organ involvement, although we found a significant but low correlation with C3. Our results and a review of the literature suggest that the increase in CD28 serum levels may be the result of CD28 gene overexpression, which could be related to the decrease in CD28+ T cells, T-cell hyporesponsiveness and immune impairment that occurs in SLE.

  12. Serum osteocalcin (BGP) levels in normal men: a longitudinal evaluation reveals an age-associated increase.

    PubMed

    Orwoll, E S; Deftos, L J

    1990-03-01

    Serum levels of bone gla protein (BGP) have been reported to increase with aging and hence to reflect an age-related increase in bone remodeling activity. To evaluate the relationship between aging and serum BGP levels in a study of longitudinal design, we measured BGP concentrations in 77 normal men at 6 month intervals over a 3 year period. Mean BGP levels at the onset (4.95 +/- 1.5 ng/ml) increased significantly during the study (p = 0.004), and the mean of individual BGP slopes was positive (0.38 +/- 0.6 ng/ml per year, p = 0.0001). The rate of change in BGP was not related to serum creatinine levels or dietary calcium intake.

  13. A Systematic Evaluation of Collagen Crosslinks in the Human Cervix

    PubMed Central

    Zork, Noelia M; Myers, Kristin Marie; Yoshida, Ms. Kyoko; Cremers, Serge; Jiang, Hongfeng; Ananth, Cande V; Wapner, Ronald; Kitajewski, Jan; Vink, Joy

    2014-01-01

    Objective The mechanical strength of the cervix relies on crosslinking of the tissue’s collagen network. Clinically, the internal os is functionally distinct from the external os. We sought to detect specific collagen crosslinks in human cervical tissue and determine if crosslink profiles were similar at the internal and external os. Study Design Transverse slices of cervical tissue were obtained at the internal and external os from 13 non-pregnant, premenopausal women undergoing a benign hysterectomy. To understand how crosslinks were distributed throughout the entire cervix and at the internal and external os, biopsies were obtained from three circumferential zones in four quadrants from each slice. Biopsies were pulverized, lyophilized, reduced with sodium borohydride, hydrolyzed with hydrochloric acid and reconstituted in heptafluorobutyric acid buffer. Hydroxyproline was measured by ultra-performance liquid chromatography-electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS), converted to total collagen, and normalized by dry weight. Collagen crosslinks pyridinoline (PYD), deoxypyridinoline (DPD), dihydroxylysinonorleucine (DHLNL), and the nonenzymatic advanced glycation end product pentosidine [PEN] were measured by UPLC-ESI-MS/MS and reported as crosslink density ratio (crosslink:total collagen). Generalized estimated equation analysis was used to compare results between the internal and external os and to compare quadrants and zones within slices from the internal and external os to determine if crosslink profiles were similar. Results 592 samples from 13 patients were analyzed. Collagen crosslinks are detectable in the human cervix by UPLC-ESI-MS/MS. When comparing all samples from the internal and external os, similar levels of collagen content, PYD, DHLNL and DPD were found but PEN density was higher at the external os (0.005 vs 0.004, P=0.001). When comparing all internal os samples, significant heterogeneity was found in collagen content

  14. Magnesium deficiency increases serum fibroblast growth factor-23 levels in rats.

    PubMed

    Matsuzaki, Hiroshi; Kajita, Yasutaka; Miwa, Misao

    2013-01-01

    A magnesium (Mg)-deficient diet results in decreased serum phosphorus (P) levels and increased urinary P excretion; however, the mechanisms responsible for these effects are unclear. Fibroblast growth factor-23 (FGF-23) is a potent regulator of P homeostasis. To determine the mechanisms responsible for the change in serum levels and urinary excretion of P with Mg deficiency, the present study examined the effects of Mg deficiency on serum FGF-23 levels. Male rats were randomized by weight into two groups and fed a control diet (Mg concentration: 0.05%) or a Mg-deficient diet (Mg concentration: Mg-free) for 21 days. Serum P levels in rats fed the Mg-deficient diet were significantly lower than in rats fed the control diet. Furthermore, urinary P excretion was significantly higher in rats fed the Mg-deficient diet compared to rats fed the control diet. Conversely, the tubular reabsorption rate of P was significantly lower in rats fed the Mg-deficient diet than in the controls. Serum FGF-23 levels in rats fed the Mg-deficient diet were significantly higher than those in animals fed the control diet. The results from the present study indicate that 1) Mg deficiency increases serum FGF-23 levels; and 2) Mg deficiency causes increased urinary P excretion via inhibition of renal P reabsorption, resulting in a lowering of serum P levels. Moreover, we suggest that the high serum FGF-23 levels induced by Mg deficiency contribute to the decrease in renal P reabsorption.

  15. Arsenic increased lipid peroxidation in rat tissues by a mechanism independent of glutathione levels.

    PubMed Central

    Ramos, O; Carrizales, L; Yáñez, L; Mejía, J; Batres, L; Ortíz, D; Díaz-Barriga, F

    1995-01-01

    The role of lipid peroxidation in the mechanism of arsenic toxicity was investigated in female rats pretreated with N-acetylcysteine (NAC, a glutathione [GSH] inducer) or with buthionine sulfoximine (BSO, a GSH depletor). Rats were challenged with sodium arsenite, and sacrificed 1 hr after this treatment. Results showed that arsenic decreased GSH levels and increased lipid peroxidation in liver, kidney, and heart, with a larger effect at 18.2 mg/kg than at 14.8 mg/kg for lipid peroxidation induction. In the liver of rats treated with arsenic, pretreatment with NAC increased the levels of GSH and decreased lipid peroxidation. In kidney and heart, NAC pretreatment protected the tissues against arsenic-induced depletion of GSH levels, but the same degree of protection was not found for lipid peroxidation induction. In its turn, BSO had an additive effect with arsenic in lowering the levels of GSH in the liver and kidney, but an inverse correlation between GSH levels and lipid peroxidation was found only in liver. Arsenic content in tissues of rats pretreated with NAC was lower than in rats treated only with arsenic. In rats with depleted levels of GSH (BSO-pretreated rats), a shift in arsenic tissue distribution was found, with higher levels in skin and lower levels in kidney. A clear tendency for a positive correlation between arsenic concentration and lipid peroxidation levels was found in liver, kidney, and heart. PMID:7621808

  16. Epoxy Crosslinked Silica Aerogels (X-Aerogels)

    NASA Technical Reports Server (NTRS)

    fabrizio, Eve; Ilhan, Faysal; Meador, Mary Ann; Johnston, Chris; Leventis, Nicholas

    2004-01-01

    NASA is interested in the development of strong lightweight materials for the dual role of thermal insulator and structural component for space vehicles; freeing more weight for useful payloads. Aerogels are very-low density materials (0.010 to 0.5 g/cc) that, due to high porosity (meso- and microporosity), can be, depending on the chemical nature of the network, ideal thermal insulators (thermal conductivity approx. 15 mW/mK). However, aerogels are extremely fragile. For practical application of aerogels, one must increase strength without compromising the physical properties attributed to low density. This has been achieved by templated growth of an epoxy polymer layer that crosslinks the "pearl necklace" network of nanoparticles: the framework of a typical silica aerogel. The requirement for conformal accumulation of the epoxy crosslinker is reaction both with the surface of silica and with itself. After cross-linking, the strength of a typical aerogel monolith increases by a factor of 200, in the expense of only a 2-fold increase in density. Strength is increased further by coupling residual unreacted epoxides with diamine.

  17. Modeling Caspian Sea water level oscillations under different scenarios of increasing atmospheric carbon dioxide concentrations.

    PubMed

    Roshan, Gholamreza; Moghbel, Masumeh; Grab, Stefan

    2012-12-12

    The rapid rise of Caspian Sea water level (about 2.25 meters since 1978) has caused much concern to all five surrounding countries, primarily because flooding has destroyed or damaged buildings and other engineering structures, roads, beaches and farm lands in the coastal zone. Given that climate, and more specifically climate change, is a primary factor influencing oscillations in Caspian Sea water levels, the effect of different climate change scenarios on future Caspian Sea levels was simulated. Variations in environmental parameters such as temperature, precipitation, evaporation, atmospheric carbon dioxide and water level oscillations of the Caspian sea and surrounding regions, are considered for both past (1951-2006) and future (2025-2100) time frames. The output of the UKHADGEM general circulation model and five alternative scenarios including A1CAI, BIASF, BIMES WRE450 and WRE750 were extracted using the MAGICC SCENGEN Model software (version 5.3). The results suggest that the mean temperature of the Caspian Sea region (Bandar-E-Anzali monitoring site) has increased by ca. 0.17°C per decade under the impacts of atmospheric carbon dioxide changes (r=0.21). The Caspian Sea water level has increased by ca. +36cm per decade (r=0.82) between the years 1951-2006. Mean results from all modeled scenarios indicate that the temperature will increase by ca. 3.64°C and precipitation will decrease by ca. 10% (182 mm) over the Caspian Sea, whilst in the Volga river basin, temperatures are projected to increase by ca. 4.78°C and precipitation increase by ca. 12% (58 mm) by the year 2100. Finally, statistical modeling of the Caspian Sea water levels project future water level increases of between 86 cm and 163 cm by the years 2075 and 2100, respectively.

  18. Modeling Caspian Sea water level oscillations under different scenarios of increasing atmospheric carbon dioxide concentrations

    PubMed Central

    2012-01-01

    The rapid rise of Caspian Sea water level (about 2.25 meters since 1978) has caused much concern to all five surrounding countries, primarily because flooding has destroyed or damaged buildings and other engineering structures, roads, beaches and farm lands in the coastal zone. Given that climate, and more specifically climate change, is a primary factor influencing oscillations in Caspian Sea water levels, the effect of different climate change scenarios on future Caspian Sea levels was simulated. Variations in environmental parameters such as temperature, precipitation, evaporation, atmospheric carbon dioxide and water level oscillations of the Caspian sea and surrounding regions, are considered for both past (1951-2006) and future (2025-2100) time frames. The output of the UKHADGEM general circulation model and five alternative scenarios including A1CAI, BIASF, BIMES WRE450 and WRE750 were extracted using the MAGICC SCENGEN Model software (version 5.3). The results suggest that the mean temperature of the Caspian Sea region (Bandar-E-Anzali monitoring site) has increased by ca. 0.17°C per decade under the impacts of atmospheric carbon dioxide changes (r=0.21). The Caspian Sea water level has increased by ca. +36cm per decade (r=0.82) between the years 1951-2006. Mean results from all modeled scenarios indicate that the temperature will increase by ca. 3.64°C and precipitation will decrease by ca. 10% (182 mm) over the Caspian Sea, whilst in the Volga river basin, temperatures are projected to increase by ca. 4.78°C and precipitation increase by ca. 12% (58 mm) by the year 2100. Finally, statistical modeling of the Caspian Sea water levels project future water level increases of between 86 cm and 163 cm by the years 2075 and 2100, respectively. PMID:23369617

  19. Empagliflozin, via Switching Metabolism Toward Lipid Utilization, Moderately Increases LDL Cholesterol Levels Through Reduced LDL Catabolism.

    PubMed

    Briand, François; Mayoux, Eric; Brousseau, Emmanuel; Burr, Noémie; Urbain, Isabelle; Costard, Clément; Mark, Michael; Sulpice, Thierry

    2016-07-01

    In clinical trials, a small increase in LDL cholesterol has been reported with sodium-glucose cotransporter 2 (SGLT2) inhibitors. The mechanisms by which the SGLT2 inhibitor empagliflozin increases LDL cholesterol levels were investigated in hamsters with diet-induced dyslipidemia. Compared with vehicle, empagliflozin 30 mg/kg/day for 2 weeks significantly reduced fasting blood glucose by 18%, with significant increase in fasting plasma LDL cholesterol, free fatty acids, and total ketone bodies by 25, 49, and 116%, respectively. In fasting conditions, glycogen hepatic levels were further reduced by 84% with empagliflozin, while 3-hydroxy-3-methylglutaryl-CoA reductase activity and total cholesterol hepatic levels were 31 and 10% higher, respectively (both P < 0.05 vs. vehicle). A significant 20% reduction in hepatic LDL receptor protein expression was also observed with empagliflozin. Importantly, none of these parameters were changed by empagliflozin in fed conditions. Empagliflozin significantly reduced the catabolism of (3)H-cholesteryl oleate-labeled LDL injected intravenously by 20%, indicating that empagliflozin raises LDL levels through reduced catabolism. Unexpectedly, empagliflozin also reduced intestinal cholesterol absorption in vivo, which led to a significant increase in LDL- and macrophage-derived cholesterol fecal excretion (both P < 0.05 vs. vehicle). These data suggest that empagliflozin, by switching energy metabolism from carbohydrate to lipid utilization, moderately increases ketone production and LDL cholesterol levels. Interestingly, empagliflozin also reduces intestinal cholesterol absorption, which in turn promotes LDL- and macrophage-derived cholesterol fecal excretion. PMID:27207551

  20. Empagliflozin, via Switching Metabolism Toward Lipid Utilization, Moderately Increases LDL Cholesterol Levels Through Reduced LDL Catabolism.

    PubMed

    Briand, François; Mayoux, Eric; Brousseau, Emmanuel; Burr, Noémie; Urbain, Isabelle; Costard, Clément; Mark, Michael; Sulpice, Thierry

    2016-07-01

    In clinical trials, a small increase in LDL cholesterol has been reported with sodium-glucose cotransporter 2 (SGLT2) inhibitors. The mechanisms by which the SGLT2 inhibitor empagliflozin increases LDL cholesterol levels were investigated in hamsters with diet-induced dyslipidemia. Compared with vehicle, empagliflozin 30 mg/kg/day for 2 weeks significantly reduced fasting blood glucose by 18%, with significant increase in fasting plasma LDL cholesterol, free fatty acids, and total ketone bodies by 25, 49, and 116%, respectively. In fasting conditions, glycogen hepatic levels were further reduced by 84% with empagliflozin, while 3-hydroxy-3-methylglutaryl-CoA reductase activity and total cholesterol hepatic levels were 31 and 10% higher, respectively (both P < 0.05 vs. vehicle). A significant 20% reduction in hepatic LDL receptor protein expression was also observed with empagliflozin. Importantly, none of these parameters were changed by empagliflozin in fed conditions. Empagliflozin significantly reduced the catabolism of (3)H-cholesteryl oleate-labeled LDL injected intravenously by 20%, indicating that empagliflozin raises LDL levels through reduced catabolism. Unexpectedly, empagliflozin also reduced intestinal cholesterol absorption in vivo, which led to a significant increase in LDL- and macrophage-derived cholesterol fecal excretion (both P < 0.05 vs. vehicle). These data suggest that empagliflozin, by switching energy metabolism from carbohydrate to lipid utilization, moderately increases ketone production and LDL cholesterol levels. Interestingly, empagliflozin also reduces intestinal cholesterol absorption, which in turn promotes LDL- and macrophage-derived cholesterol fecal excretion.

  1. Collagen cross-linking treatment effects on corneal dynamic biomechanical properties.

    PubMed

    Hatami-Marbini, Hamed; Rahimi, Abdolrasol

    2015-06-01

    Cornea is a soft tissue with the principal function of transmitting and refracting light rays. The objective of the current study was to characterize possible effects of the riboflavin/UVA collagen cross-linking on corneal dynamic properties. The original corneal cross-linking protocol was used to induce cross-links in the anterior portion of the bovine cornea. A DMA machine was used to conduct mechanical tensile experiments at different levels of tensile strains. The samples were divided into a control group (n = 5) and a treated group (n = 5). All specimens were first stretched to a strain of 5% and allowed to relax for twenty minutes. After completion of the stress-relaxation experiment, a frequency sweep test with oscillations ranging from 0.01 to 10 Hz was performed. The same procedure was repeated to obtain the stress-relaxation and dynamic properties at 10% strain. It was observed that the collagen cross-linking therapy significantly increased the immediate and equilibrium tensile behavior of the bovine cornea (P < 0.05). Furthermore, for all samples in control and treated groups and throughout the whole range of frequencies, a significantly larger tensile storage modulus was measured at an axial strain of 10% compared to what was obtained at a tensile strain of 5%. Finally, it was noted that although this treatment procedure resulted in a significant increase in the storage and loss modulus at any axial strain and frequency (P < 0.05), it significantly reduced the ratio of the dissipated and stored energy during a single cycle of deformation. Therefore, it was concluded that while the riboflavin/UVA collagen cross-linking increased significantly corneal stiffness, it decreased significantly its damping capability and deformability. This reduced damping ability might adversely interfere with corneal mechanical performance.

  2. Increased Heme Levels in the Heart Lead to Exacerbated Ischemic Injury

    PubMed Central

    Sawicki, Konrad Teodor; Shang, Meng; Wu, Rongxue; Chang, Hsiang-Chun; Khechaduri, Arineh; Sato, Tatsuya; Kamide, Christine; Liu, Ting; Naga Prasad, Sathyamangla V; Ardehali, Hossein

    2015-01-01

    Background Heme is an essential iron-containing molecule for cardiovascular physiology, but in excess it may increase oxidative stress. Failing human hearts have increased heme levels, with upregulation of the rate-limiting enzyme in heme synthesis, δ-aminolevulinic acid synthase 2 (ALAS2), which is normally not expressed in cardiomyocytes. We hypothesized that increased heme accumulation (through cardiac overexpression of ALAS2) leads to increased oxidative stress and cell death in the heart. Methods and Results We first showed that ALAS2 and heme levels are increased in the hearts of mice subjected to coronary ligation. To determine the causative role of increased heme in the development of heart failure, we generated transgenic mice with cardiac-specific overexpression of ALAS2. While ALAS2 transgenic mice have normal cardiac function at baseline, their hearts display increased heme content, higher oxidative stress, exacerbated cell death, and worsened cardiac function after coronary ligation compared to nontransgenic littermates. We confirmed in cultured cardiomyoblasts that the increased oxidative stress and cell death observed with ALAS2 overexpression is mediated by increased heme accumulation. Furthermore, knockdown of ALAS2 in cultured cardiomyoblasts exposed to hypoxia reversed the increases in heme content and cell death. Administration of the mitochondrial antioxidant MitoTempo to ALAS2-overexpressing cardiomyoblasts normalized the elevated oxidative stress and cell death levels to baseline, indicating that the effects of increased ALAS2 and heme are through elevated mitochondrial oxidative stress. The clinical relevance of these findings was supported by the finding of increased ALAS2 induction and heme accumulation in failing human hearts from patients with ischemic cardiomyopathy compared to nonischemic cardiomyopathy. Conclusions Heme accumulation is detrimental to cardiac function under ischemic conditions, and reducing heme in the heart may be a

  3. High D-dimer levels increase the likelihood of pulmonary embolism.

    PubMed

    Tick, L W; Nijkeuter, M; Kramer, M H H; Hovens, M M C; Büller, H R; Leebeek, F W G; Huisman, M V

    2008-08-01

    Objective. To determine the utility of high quantitative D-dimer levels in the diagnosis of pulmonary embolism. Methods. D-dimer testing was performed in consecutive patients with suspected pulmonary embolism. We included patients with suspected pulmonary embolism with a high risk for venous thromboembolism, i.e. hospitalized patients, patients older than 80 years, with malignancy or previous surgery. Presence of pulmonary embolism was based on a diagnostic management strategy using a clinical decision rule (CDR), D-dimer testing and computed tomography. Results. A total of 1515 patients were included with an overall pulmonary embolism prevalence of 21%. The pulmonary embolism prevalence was strongly associated with the height of the D-dimer level, and increased fourfold with D-dimer levels greater than 4000 ng mL(-1) compared to levels between 500 and 1000 ng mL(-1). Patients with D-dimer levels higher than 2000 ng mL(-1) and an unlikely CDR had a pulmonary embolism prevalence of 36%. This prevalence is comparable to the pulmonary embolism likely CDR group. When D-dimer levels were above 4000 ng mL(-1), the observed pulmonary embolism prevalence was very high, independent of CDR score. Conclusion. Strongly elevated D-dimer levels substantially increase the likelihood of pulmonary embolism. Whether this should translate into more intensive diagnostic and therapeutic measures in patients with high D-dimer levels irrespective of CDR remains to be studied. PMID:18452520

  4. Cortical injury increases cholesterol 24S hydroxylase (Cyp46) levels in the rat brain.

    PubMed

    Cartagena, Casandra M; Ahmed, Farid; Burns, Mark P; Pajoohesh-Ganji, Ahdeah; Pak, Daniel T; Faden, Alan I; Rebeck, G William

    2008-09-01

    In traumatic brain injury (TBI), cellular loss from initial impact as well as secondary neurodegeneration leads to increased cholesterol and lipid debris at the site of injury. Cholesterol accumulation in the periphery can trigger inflammatory mechanisms while cholesterol clearance may be anti-inflammatory. Here we investigated whether TBI altered the regulation of cholesterol 24S-hydroxylase (Cyp46), an enzyme that converts cholesterol to the more hydrophilic 24S-hydroxycholesterol. We examined by Western blot and immunohistochemistry changes in Cyp46 expression following fluid percussion injury. Under normal conditions, most Cyp46 was present in neurons, with very little measurable in glia. Cyp46 levels were significantly increased at 7 days post-injury, and cell type specific analysis at 3 days post-injury showed a significant increase in levels of Cyp46 (84%) in microglia. Since 24-hydroxycholesterol induces activation of genes through the liver X receptor (LXR), we examined protein levels of ATP-binding cassette transporter A1 and apolipoprotein E, two LXR regulated cholesterol homeostasis proteins. Apolipoprotein E and ATP-binding cassette transporter A1 were increased at 7 days post-injury, indicating that increased LXR activity coincided with increased Cyp46 levels. We found that activation of primary rat microglia by LPS in vitro caused increased Cyp46 levels. These data suggest that increased microglial Cyp46 activity is part of a system for removal of damaged cell membranes post-injury, by conversion of cholesterol to 24-hydroxycholesterol and by activation of LXR-regulated gene transcription.

  5. Laser crosslink configurations for RF satellite communications systems

    NASA Astrophysics Data System (ADS)

    Sebacher, K. S.; Lambert, S. G.; Pautler, J. A.; Carter, J. P.

    Predictions of future satellite communications traffic indicate that an increased capacity for satellite communications systems is required. Crosslinks between satellites provide improvements in communications throughput for these systems. Crosslinks also increase system flexibility and remove the dependence of world-wide information flow on relay ground stations located outside the continental United States. Laser crosslinks provide the additional advantage of eliminating susceptibility to space-based or ground-based jammers. Laser terminals are also smaller and require smaller antennas than an RF terminal. This paper describes the advantages of adding laser crosslinks to RF satellite communications systems. Characteristics of the required RF/optical interfaces on-board the satellites are addessed. Terminal configurations that provide reliable, accurate laser communications at high data rates are described.

  6. Stress-induced increases in brainstem amino acid levels are prevented by chronic sodium hydrosulfide treatment.

    PubMed

    Warenycia, M W; Kombian, S B; Reiffenstein, R J

    1990-01-01

    Neurotransmitter amino acid levels were measured in select brain regions of rats and mice after chronic treatment with sublethal doses of sodium hydrosulfide (NaHS). Brainstem aspartate, glutamate, glutamine, taurine and GABA levels increased in chronically but not acutely saline-treated rats. These increases may have been due to stress from frequent handling, and were prevented by chronic NaHS treatment (7.5 mg/kg ip every 8 hr for 3 consecutive days). In contrast, aspartate, glutamate and glutamine increased in female but not in male ICR mouse brainstems after once daily treatment with 7.0 mg/kg NaHS for 5 consecutive days. These effects of NaHS may indicate chronic low level H2S neurotoxicity. Differences between chronic and acute treatments, female and male responses, and treatment paradigms may complicate interpretations of such toxicity studies.

  7. Nutrient levels modify saltmarsh responses to increased inundation in different soil types.

    PubMed

    Wong, Joanne X W; Van Colen, Carl; Airoldi, Laura

    2015-03-01

    Saltmarshes have been depleted historically, and cumulative stressors threaten their future persistence. We examined experimentally how nutrient availability (high vs. low) affects the responses of Spartina maritima to increased inundation in two mineral soil types (low vs. medium organic). Increased inundation, one of the effects of accelerated sea level rise, had negative effects on most plant growth parameters, but the magnitude varied with soil and nutrient levels, and between plants from different locations. Average differences between inundation treatments were largest at high nutrient conditions in low organic matter soils. We conclude that saltmarsh vegetation would be more drastically affected by increased inundation in low than in medium organic matter soils, and especially in estuaries already under high nutrient availability. This knowledge enhances the prediction of changes at the foreshore of saltmarshes related to sea level rise, and the development of site-specific conservation strategies.

  8. Stimulation of calcitonin secretory capacity by increased serum levels of testosterone in men treated with tamoxifen.

    PubMed

    Schopman, W; Slager, E; Hackeng, W H; Mulder, H

    1987-12-01

    Previous studies have suggested that sex steroids, including both oestrogen and testosterone, influence calcitonin secretion. However, a negative effect of gonadotrophins on calcitonin has not been excluded. Twelve men with infertility and low-normal serum levels of testosterone were studied before and during tamoxifen therapy. Increases in the serum levels of LH, FSH, testosterone and calcitonin were observed after treatment. Our findings suggest that testosterone has a direct influence on calcitonin secretion. PMID:3123401

  9. Increase of intracellular cisplatin levels and radiosensitization by ultrasound in combination with microbubbles.

    PubMed

    Lammertink, Bart H A; Bos, Clemens; van der Wurff-Jacobs, Kim M; Storm, Gert; Moonen, Chrit T; Deckers, Roel

    2016-09-28

    The possibility to enhance drug delivery by using ultrasound in combination with microbubbles (USMB) is extensively studied. So far, these studies have focused on the delivery and efficacy of a single drug, e.g. in chemotherapy. In this study, we investigated the intracellular delivery of cisplatin by USMB and the subsequent increased efficacy in combination with radiotherapy in a head and neck cancer cell line in vitro. After USMB-mediated intracellular delivery was verified using the model-drug SYTOX® Green, we investigated the efficacy of cisplatin when combined with USMB and radiotherapy and measured whether intracellular cisplatin concentration was enhanced after applying USMB. In addition, the effect of USMB on cisplatin and radiotherapy-induced DNA damage was studied. Flow cytometry showed that USMB treatment increased the average percentage SYTOX® Green positive cells from 2.2% to 34.5%. Clonogenic assays demonstrated that exposure to USMB significantly increased the efficacy of cisplatin combined with radiotherapy. The enhanced efficacy was associated with increased intracellular cisplatin levels, which were 2.7-fold higher when cisplatin was combined with USMB. As a result, an 82% increase in levels of DNA double strand breaks was found when cisplatin was combined with USMB, compared to cisplatin only (p<0.05). In conclusion, cisplatin uptake was significantly increased by USMB, which resulted in enhanced levels of DNA damage and increased efficacy of cisplatin in combination with radiotherapy in vitro. PMID:27476609

  10. Calpain expression in lymphoid cells. Increased mRNA and protein levels after cell activation.

    PubMed

    Deshpande, R V; Goust, J M; Chakrabarti, A K; Barbosa, E; Hogan, E L; Banik, N L

    1995-02-10

    Although calpain is ubiquitously present in human tissues and is thought to play a role in demyelination, its activity is very low in resting normal lymphocytes. To determine the nature of calpain expression at the mRNA and protein levels in human lymphoid cells, we studied human T lymphocytic, B lymphocytic, and monocytic lines as well as peripheral blood mononuclear cells. Stimulation of cells with the phorbol ester phorbol myristate acetate and the calcium ionophore A23187 resulted in increased calpain mRNA and protein expression. Calpain mRNA expression is also increased in human T cells stimulated with anti-CD3. A dissociation between the increases of RNA and protein suggested that calpain could be released from the cells; the subsequent experiments showed its presence in the extracellular environment. 5,6-Dichloro-1b-D-ribofuranosylbenzimidazole, a reversible inhibitor of mRNA synthesis, reduced calpain mRNA levels by 50-67% and protein levels by 72-91%. Its removal resulted in resumption of both calpain mRNA and protein synthesis. Cycloheximide, a translational inhibitor, reduced calpain protein levels by 77-81% and calpain mRNA levels by 96% in activated THP-1 cells. Interferon-gamma induced calpain mRNA and protein in U-937 and THP-1 cells. Dexamethasone increased mRNA expression in THP-1 cells. Our results indicate that activation of lymphoid cells results in de novo synthesis and secretion of calpain. PMID:7852311

  11. Interfacial Bioorthogonal Cross-Linking

    PubMed Central

    2015-01-01

    Described herein is interfacial bioorthogonal cross-linking, the use of bioorthogonal chemistry to create and pattern biomaterials through diffusion-controlled gelation at the liquid-gel interface. The basis is a rapid (k2 284000 M–1 s–1) reaction between strained trans-cyclooctene (TCO) and tetrazine (Tz) derivatives. Syringe delivery of Tz-functionalized hyaluronic acid (HA-Tz) to a bath of bis-TCO cross-linker instantly creates microspheres with a cross-linked shell through which bis-TCO diffuses freely to introduce further cross-linking at the interface. Tags can be introduced with 3D resolution without external triggers or templates. Water-filled hydrogel channels were prepared by simply reversing the order of addition. Prostate cancer cells encapsulated in the microspheres have 99% viability, proliferate readily, and form aggregated clusters. This process is projected to be useful in the fabrication of cell-instructive matrices for in vitro tissue models. PMID:25177528

  12. Cannabis use is associated with increased CCL11 plasma levels in young healthy volunteers.

    PubMed

    Fernandez-Egea, Emilio; Scoriels, Linda; Theegala, Swathi; Giro, Maria; Ozanne, Susan E; Burling, Keith; Jones, Peter B

    2013-10-01

    Cannabis is a widely used recreational drug. Its effect on human health and psychosis remains controversial. In this study, we aimed to explore the possibility that cannabis use influenced CCL11 plasma levels. Increased CCL11 chemokine has been reported in schizophrenia and cannabis is a known trigger of schizophrenia. Additionally, plasma levels of the chemokine CCL11 have recently been shown to increase with age and with cognitive deficits and hippocampal neurogenesis. For this study, a total of 87 healthy volunteers (68% men, age range 18-35 years) completed the Cannabis Experience Questionnaire that included information on sociodemographic and morphometric data and provided a blood sample for CCL11 measurement. 'Current users' of cannabis (n=18) had significantly higher CCL11 plasma levels compared to 'past users' (n=33) and 'never users' (n=36) [F(3,84)=3.649; p=0.030]. The latter two groups had similar CCL11 levels. Higher CCL11 plasma levels could not be attributed to gender, age, body mass index, physical activity or use of other legal/illegal drugs. These results suggest that cannabis use increases CCL11 plasma levels and the effects are reversible when cannabis use ceases. PMID:23820464

  13. Cannabis use is associated with increased CCL11 plasma levels in young healthy volunteers.

    PubMed

    Fernandez-Egea, Emilio; Scoriels, Linda; Theegala, Swathi; Giro, Maria; Ozanne, Susan E; Burling, Keith; Jones, Peter B

    2013-10-01

    Cannabis is a widely used recreational drug. Its effect on human health and psychosis remains controversial. In this study, we aimed to explore the possibility that cannabis use influenced CCL11 plasma levels. Increased CCL11 chemokine has been reported in schizophrenia and cannabis is a known trigger of schizophrenia. Additionally, plasma levels of the chemokine CCL11 have recently been shown to increase with age and with cognitive deficits and hippocampal neurogenesis. For this study, a total of 87 healthy volunteers (68% men, age range 18-35 years) completed the Cannabis Experience Questionnaire that included information on sociodemographic and morphometric data and provided a blood sample for CCL11 measurement. 'Current users' of cannabis (n=18) had significantly higher CCL11 plasma levels compared to 'past users' (n=33) and 'never users' (n=36) [F(3,84)=3.649; p=0.030]. The latter two groups had similar CCL11 levels. Higher CCL11 plasma levels could not be attributed to gender, age, body mass index, physical activity or use of other legal/illegal drugs. These results suggest that cannabis use increases CCL11 plasma levels and the effects are reversible when cannabis use ceases.

  14. Pistachio intake increases high density lipoprotein levels and inhibits low-density lipoprotein oxidation in rats.

    PubMed

    Aksoy, Nur; Aksoy, Mehmet; Bagci, Cahit; Gergerlioglu, H Serdar; Celik, Hakim; Herken, Emine; Yaman, Abdullah; Tarakcioglu, Mehmet; Soydinc, Serdar; Sari, Ibrahim; Davutoglu, Vedat

    2007-05-01

    There is increasing evidence that nuts have protective effects against coronary artery disease by improving lipid profile and inhibiting lipid oxidation. However, data about pistachio nuts are limited, and to our knowledge, there is no study investigating the effects of pistachio intake on lipid oxidation and serum antioxidant levels. This study, therefore, sought to determine the effects of pistachio intake on serum lipids and determine whether consumption of pistachio would alter serum antioxidant levels. Rats were randomly divided into three groups (n=12 for each): control group fed basic diet for 10 weeks and treated groups fed basic diet plus pistachio which constituted 20% and 40% of daily caloric intake, respectively. Consumption of pistachio as 20% of daily caloric intake increased high-density lipoprotein (HDL) levels and decreased total cholesterol (TC)/HDL ratio, compared with those not taking pistachio. However, TC, low-density lipoprotein (LDL) cholesterol and triglyceride levels were unaffected by pistachio consumption. Consumption of pistachio as 20% of daily caloric intake increased serum paraoxonase activity by 35% and arylesterase activity by 60%, which are known to inhibit LDL cholesterol oxidation, compared with the control group. However, increased antioxidant activity was blunted when pistachio intake was increased to 40% of daily caloric intake. In conclusion, the present results show that consumption of pistachio as 20% of daily caloric intake leads to significant improvement in HDL and TC/HDL ratio and inhibits LDL cholesterol oxidation. These results suggest that pistachio may be beneficial for both prevention and treatment of coronary artery disease.

  15. Correlation between organophosphate poisoning, acetylcholinesterase inhibition, and increased cyclic GMP levels in malathion-treated insects.

    PubMed

    Bodnaryk, R P

    1977-05-01

    Organophosphate poisoning with malathion caused large increases (up to 125 and 440%, respectively) in the level of cyclic GMP in larvae of Mamestra configurata Wlk. and in the fly Sarcophaga bullata Parker. Cyclic AMP was little affected. The malathion-induced increase in cyclic GMP was time and dose dependent. Time-course studies with the head and thorax of S. bullata demonstrated that the increase in cyclic GMP level occurred precipitously after a lag period of about 1 h, during which time the activity of acetylcholinesterase (EC 3.1.1.7) was progressively inhibited. The abrupt increase in cyclic GMP began when acetylcholinesterase activity had been inhibited to a sufficient extent to permit accumulation of acetylcholine. It is suggested that the accumulation of acetylcholine in the malathion-poisoned insects caused cyclic GMP levels to rise. Cyclic GMP may have a role in cholinergic transmission in normally functioning insect neural tissue. Increased levels of cyclic GMP induced by organophosphate and organocholorine (Bodnaryk, R. P. (1976) Can. J. Biochem. 54, 957-962) insecticides appear to be a vital and previously unrecognized biochemical lesion in insects poisoned by these compounds.

  16. Increased serum levels of sortilin are associated with depression and correlated with BDNF and VEGF

    PubMed Central

    Buttenschøn, H N; Demontis, D; Kaas, M; Elfving, B; Mølgaard, S; Gustafsen, C; Kaerlev, L; Petersen, C M; Børglum, A D; Mors, O; Glerup, S

    2015-01-01

    Neurotrophic factors have been investigated in relation to depression. The aim of the present study was to widen this focus to sortilin, a receptor involved in neurotrophic signalling. The serum sortilin level was investigated in 152 individuals with depression and 216 control individuals, and eight genetic markers located within the SORT1 gene were successfully analysed for association with depression. Genotyping was performed using the Sequenom MassARRAY platform. All the individuals returned a questionnaire and participated in a semi-structured diagnostic interview. Sortilin levels were measured by immunoassay, and potential determinants of the serum sortilin level were assessed by generalized linear models. Serum levels of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) were measured in previous studies. We identified a significant increase of serum sortilin levels in depressed individuals compared with controls (P=0.0002) and significant positive correlation between serum sortilin levels and the corresponding levels of BDNF and VEGF. None of the genotyped SNPs were associated with depression. Additional analyses showed that the serum sortilin level was influenced by several other factors. Alcohol intake and body mass index, as well as depression, serum BDNF and serum VEGF were identified as predictors of serum sortilin levels in our final multivariate model. In conclusion, the results suggest a role of circulating sortilin in depression which may relate to altered activity of neurotrophic factors. PMID:26556286

  17. A rapid increase in lipoprotein (a) levels after ethanol withdrawal in alcoholic men

    SciTech Connect

    Kervinen, K.; Savolainen, J.J.; Kesaeniemi, Y.A. )

    1991-01-01

    Plasma concentrations of lipoprotein (a) (Lp(a)) were studied in 11 male alcoholics at the end of a drinking period and monitored during subsequent abstinence. Lp(a) levels showed a daily increase for four consecutive days after the beginning of abstinence, the values for the third and the fourth day being significantly higher than those of the first day. The changes in Lp(a) showed no association with the changes in low density lipoprotein (LDL) and high density lipoprotein (HDL) cholesterol levels. In one alcoholic subject with a heterozygous form of familial hypercholesterolemia who was monitored for 11 days, the Lp(a) levels rose up to the fourth day and remained at a high level thereafter. These results suggest that ethanol ingestion may be associated with a lower of Lp(a) levels, which may contribute to the delayed progression of atherosclerosis observed in alcohol drinkers.

  18. Ultraviolet B radiation was increased at ground level in scotland during a period of ozone depletion.

    PubMed

    Moseley, H; Mackie, R M

    1997-07-01

    The potentially harmful effects associated with stratospheric ozone depletion are widely acknowledged. As the ozone layer principally absorbs ultraviolet (UV) radiation of wavelengths below 290 nm, reductions in stratospheric ozone levels are likely to result in increased UVB at the earth's surface, with the risk of increased incidence of skin cancer. Measuring the sun's spectrum at ground level requires sophisticated and reliable spectral instruments. Results are reported for this for the first time in the U.K. using spectral instruments, showing a significant increase in short wavelength UV radiation at a time of depleted stratospheric ozone. If this trend increases, future ozone depletion could contribute to known risks for cutaneous malignancies of all types.

  19. Stimulation of human Jurkat cells by monoclonal antibody crosslinking of transfected-Ly-6A.2 (TAP) molecules.

    PubMed

    McGrew, J T; Rock, K L

    1991-10-01

    Monoclonal antibody crosslinking of phosphatidylinositol-anchored Ly-6A.2 molecules on the surface of murine T lymphocytes leads to cell activation and secretion of IL-2. To examine the potential activity of these molecules in human T cells we transfected the Ly-6A.2 gene into Jurkat cells. Transfection of Jurkat cells with genomic Ly-6A.2 sequences results in low levels of Ly-6A.2 on the cell surface. However, linking the Ly-6A.2 sequences to the enhancer from the human CD2 gene results in greatly increased expression of Ly-6A.2. These molecules are anchored to the membrane via a phosphatidylinositol linkage. Crosslinking of Ly-6A.2 molecules with soluble mAb stimulates the transfected Jurkat cells to produce IL-2. This stimulation is abrogated by treatment with phosphatidylinositol-specific phospholipase C. The transfected human T cells displayed the same unusual crosslinking requirements for stimulation with anti-Ly-6A.2 mAbs as previously observed for murine T cells. Crosslinking of Ly-6A.2 with soluble antibodies is stimulatory, whereas immobilized antibodies are inactive. The crosslinking requirements for antiCD3 mAb stimulation display a reciprocal pattern. These data demonstrate that the Ly-6A.2 pathway for T cell activation is conserved between human and murine T cells.

  20. Licochalcone A induces T24 bladder cancer cell apoptosis by increasing intracellular calcium levels.

    PubMed

    Yang, Xinhui; Jiang, Jiangtao; Yang, Xinyan; Han, Jichun; Zheng, Qiusheng

    2016-07-01

    Licochalcone A (LCA) has been reported to significantly inhibit cell proliferation, increase reactive oxygen species (ROS) levels, and induce apoptosis of T24 human bladder cancer cells via mitochondria and endoplasmic reticulum (ER) stress-triggered signaling pathways. Based on these findings, the present study aimed to investigate the mechanisms by which LCA induces apoptosis of T24 cells. Cultured T24 cells were treated with LCA, and cell viability was measured using the sulforhodamine B assay. Apoptosis was detected by flow cytometry with Annexin V/propidium iodide staining, and by fluorescent microscopy with Hoechst 33258 staining. The levels of intracellular free calcium ions were determined using Fluo-3 AM dye marker. Intracellular ROS levels were assessed using the 2',7'-dichlorodihydrofluorescein diacetate probe assay. The mitochondrial membrane potential was measured using 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethyl benzimidazole carbocyanine iodide. Furthermore, the mRNA expression levels of B‑cell lymphoma (Bcl)‑extra large, Bcl‑2‑associated X protein, Bcl‑2‑interacting mediator of cell death, apoptotic protease activating factor‑1 (Apaf‑1), calpain 2, cysteinyl aspartate specific proteinase (caspase)‑3, caspase‑4 and caspase‑9 were determined using reverse transcription semiquantitative and quantitative polymerase chain reaction analyses. Treatment with LCA inhibited proliferation and induced apoptosis of T24 cells, and increased intracellular Ca2+ levels and ROS production. Furthermore, LCA induced mitochondrial dysfunction, decreased mitochondrial membrane potential, and increased the mRNA expression levels of Apaf‑1, caspase‑9 and caspase‑3. Exposure of T24 cells to LCA also triggered calpain 2 and caspase‑4 activation, resulting in apoptosis. These findings indicated that LCA increased intracellular Ca2+ levels, which may be associated with mitochondrial dysfunction. In addition, the ER stress pathway may be

  1. Projected carbon dioxide to increase grass pollen and allergen exposure despite higher ozone levels.

    PubMed

    Albertine, Jennifer M; Manning, William J; DaCosta, Michelle; Stinson, Kristina A; Muilenberg, Michael L; Rogers, Christine A

    2014-01-01

    One expected effect of climate change on human health is increasing allergic and asthmatic symptoms through changes in pollen biology. Allergic diseases have a large impact on human health globally, with 10-30% of the population affected by allergic rhinitis and more than 300 million affected by asthma. Pollen from grass species, which are highly allergenic and occur worldwide, elicits allergic responses in 20% of the general population and 40% of atopic individuals. Here we examine the effects of elevated levels of two greenhouse gases, carbon dioxide (CO2), a growth and reproductive stimulator of plants, and ozone (O3), a repressor, on pollen and allergen production in Timothy grass (Phleum pratense L.). We conducted a fully factorial experiment in which plants were grown at ambient and/or elevated levels of O3 and CO2, to simulate present and projected levels of both gases and their potential interactive effects. We captured and counted pollen from flowers in each treatment and assayed for concentrations of the allergen protein, Phl p 5. We found that elevated levels of CO2 increased the amount of grass pollen produced by ∼50% per flower, regardless of O3 levels. Elevated O3 significantly reduced the Phl p 5 content of the pollen but the net effect of rising pollen numbers with elevated CO2 indicate increased allergen exposure under elevated levels of both greenhouse gases. Using quantitative estimates of increased pollen production and number of flowering plants per treatment, we estimated that airborne grass pollen concentrations will increase in the future up to ∼200%. Due to the widespread existence of grasses and the particular importance of P. pratense in eliciting allergic responses, our findings provide evidence for significant impacts on human health worldwide as a result of future climate change.

  2. Projected carbon dioxide to increase grass pollen and allergen exposure despite higher ozone levels.

    PubMed

    Albertine, Jennifer M; Manning, William J; DaCosta, Michelle; Stinson, Kristina A; Muilenberg, Michael L; Rogers, Christine A

    2014-01-01

    One expected effect of climate change on human health is increasing allergic and asthmatic symptoms through changes in pollen biology. Allergic diseases have a large impact on human health globally, with 10-30% of the population affected by allergic rhinitis and more than 300 million affected by asthma. Pollen from grass species, which are highly allergenic and occur worldwide, elicits allergic responses in 20% of the general population and 40% of atopic individuals. Here we examine the effects of elevated levels of two greenhouse gases, carbon dioxide (CO2), a growth and reproductive stimulator of plants, and ozone (O3), a repressor, on pollen and allergen production in Timothy grass (Phleum pratense L.). We conducted a fully factorial experiment in which plants were grown at ambient and/or elevated levels of O3 and CO2, to simulate present and projected levels of both gases and their potential interactive effects. We captured and counted pollen from flowers in each treatment and assayed for concentrations of the allergen protein, Phl p 5. We found that elevated levels of CO2 increased the amount of grass pollen produced by ∼50% per flower, regardless of O3 levels. Elevated O3 significantly reduced the Phl p 5 content of the pollen but the net effect of rising pollen numbers with elevated CO2 indicate increased allergen exposure under elevated levels of both greenhouse gases. Using quantitative estimates of increased pollen production and number of flowering plants per treatment, we estimated that airborne grass pollen concentrations will increase in the future up to ∼200%. Due to the widespread existence of grasses and the particular importance of P. pratense in eliciting allergic responses, our findings provide evidence for significant impacts on human health worldwide as a result of future climate change. PMID:25372614

  3. Evaluating Dimethyldiethoxysilane for use in Polyurethane Crosslinked Silica Aerogels

    NASA Technical Reports Server (NTRS)

    Randall, Jason P.; Meador, Mary Ann B.; Jana, Sadhan C.

    2008-01-01

    Silica aerogels are highly porous materials which exhibit exceptionally low density and thermal conductivity. Their "pearl necklace" nanostructure, however, is inherently weak; most silica aerogels are brittle and fragile. The strength of aerogels can be improved by employing an additional crosslinking step using isocyanates. In this work, dimethyldiethoxysilane (DMDES) is evaluated for use in the silane backbone of polyurethane crosslinked aerogels. Approximately half of the resulting aerogels exhibited a core/shell morphology of hard crosslinked aerogel surrounding a softer, uncrosslinked center. Solid state NMR and scanning electron microscopy results indicate the DMDES incorporated itself as a conformal coating around the outside of the secondary silica particles, in much the same manner as isocyanate crosslinking. Response surface curves were generated from compression data, indicating levels of reinforcement comparable to that in previous literature, despite the core/shell morphology.

  4. Increased O-GlcNAc Levels Correlate with Decreased O-GlcNAcase Levels in Alzheimer Disease Brain

    PubMed Central

    Förster, Sarah; Welleford, Andrew S.; Triplett, Judy C.; Sultana, Rukhsana; Schmitz, Brigitte; Butterfield, D. Allan

    2014-01-01

    The potential role of the posttranslational modification of proteins with O-linked N-acetyl-β-D-glucosamine (O-GlcNAc) in the pathogenesis of Alzheimer disease (AD) has been studied extensively, yet the exact function of O-GlcNAc in AD remains elusive. O-GlcNAc cycling is facilitated by only two highly conserved enzymes: O-GlcNAc transferase (OGT) catalyzes the addition, while O-GlcNAcase (OGA) catalyzes the removal of GlcNAc from proteins. Studies analyzing global O-GlcNAc levels in AD brain have produced inconsistent results and the reasons for altered O-GlcNAcylation in AD are still poorly understood. In this study, we show a 1.2 fold increase in cytosolic protein O-GlcNAc modification in AD brain when compared to age-matched controls. Interestingly, O-GlcNAc changes seem to be attributable to differential modification of a few individual proteins. While our finding of augmented O-GlcNAcylation concurs with some reports, it is contrary to others demonstrating decreased O-GlcNAc levels in AD brain. These conflicting results emphasize the need for further studies providing conclusive evidence on the subject of O-GlcNAcylation in AD. We further demonstrate that, while OGT protein levels are unaffected in AD, OGA protein levels are significantly decreased to 75 % of those in control samples. In addition, augmented protein O-GlcNAc modification correlates to decreased OGA protein levels in AD subjects. While OGA inhibitors are already being tested for AD treatment, our results provide a strong indication that the general subject of O-GlcNAcylation and specifically its regulation by OGA and OGT in AD need further investigation to conclusively elucidate its potential role in AD pathogenesis and treatment. PMID:24859566

  5. Hydrazone Self-Crosslinking of Multiphase Elastin-Like Block Copolymer Networks

    PubMed Central

    Krishna, Urlam Murali; Martinez, Adam W.; Caves, Jeffrey M.; Chaikof, Elliot L.

    2011-01-01

    Biosynthetic strategies for the production of recombinant elastin-like protein (ELP) triblock copolymers have resulted in elastomeric protein hydrogels, formed through rapid physical crosslinking upon warming of concentrated solutions. However, the strength of physically crosslinked networks can be limited, and options for non-toxic chemical crosslinking of these networks are not optimal. In this report, we modify two recombinant elastin-like proteins with aldehyde and hydrazide functionalities. When combined, these modified recombinant proteins self-crosslink through hydrazone bonding without requiring initiators or producing by-products. Crosslinked materials are evaluated for water content and swelling upon hydration, and subject to tensile and compressive mechanical tests. Hydrazone crosslinking is a viable method for increasing the mechanical strength of elastin-like protein polymers, in a manner that is likely to lend itself to the biocompatible in situ formation of chemically and physically crosslinked ELP hydrogels. PMID:22154858

  6. Increased platelet oxidative metabolism, blood oxidative stress and neopterin levels after ultra-endurance exercise.

    PubMed

    de Lucas, Ricardo Dantas; Caputo, Fabrizio; Mendes de Souza, Kristopher; Sigwalt, André Roberto; Ghisoni, Karina; Lock Silveira, Paulo Cesar; Remor, Aline Pertile; da Luz Scheffer, Débora; Guglielmo, Luiz Guilherme Antonacci; Latini, Alexandra

    2014-01-01

    The purpose of the present investigation was to identify muscle damage, inflammatory response and oxidative stress blood markers in athletes undertaking the ultra-endurance MultiSport Brazil race. Eleven well-trained male athletes (34.3 ± 3.1 years, 74.0 ± 7.6 kg; 172.2 ± 5.1 cm) participated in the study and performed the race, which consisted of about 90 km of alternating off-road running, mountain biking and kayaking. Twelve hours before and up to 15 minutes after the race a 10 mL blood sample was drawn in order to measure the following parameters: lactate dehydrogenase and creatine kinase activities, lipid peroxidation, catalase activity, protein carbonylation, respiratory chain complexes I, II and IV activities, oxygen consumption and neopterin concentrations. After the race, plasma lactate dehydrogenase and creatine kinase activities were significantly increased. Erythrocyte TBA-RS levels and plasma protein carbonylation were markedly augmented in post-race samples. Additionally, mitochondrial complex II activity and oxygen consumption in post-race platelet-rich plasma were also increased. These altered biochemical parameters were accompanied by increased plasma neopterin levels. The ultra-endurance event provoked systemic inflammation (increased neopterin) accompanied by marked oxidative stress, likely by increasing oxidative metabolism (increased oxidative mitochondrial function). This might be advantageous during prolonged exercise, mainly for efficient substrate oxidation at the mitochondrial level, even when tissue damage is induced.

  7. Physical crosslinkings of edible collagen casing.

    PubMed

    Wang, Wenhang; Zhang, Yi; Ye, Ran; Ni, Yonghao

    2015-11-01

    Although edible collagen casing has been commercially used in meat industry, the safety and effectiveness of collagen cross-linking with minimally invasive treatments are still big concerns for manufacturers. In this study, ultraviolet irradiation (UV) and dehydrothermal treatment (DHT) were used to improve the properties of casing. UV, DHT, and their combination (UV+DHT) significantly increased tensile strength and decreased elongation at break of casing, in which DHT showed the best performance. Swelling of casing was also partially inhibited by the treatments. Furthermore, UV and DHT slightly improved thermal stability of the casings. In addition, X-ray diffraction patterns showed the treatments caused different extents of denaturation of collagen. No obvious effects in thickness and light transparency except for surface roughness were observed in the treated casings. The physical treatments could potentially be used as safe and effective alternatives to chemical cross-linking for the production of collage casing.

  8. Bilirubin Increases Insulin Sensitivity by Regulating Cholesterol Metabolism, Adipokines and PPARγ Levels.

    PubMed

    Liu, Jinfeng; Dong, Huansheng; Zhang, Yong; Cao, Mingjun; Song, Lili; Pan, Qingjie; Bulmer, Andrew; Adams, David B; Dong, Xiao; Wang, Hongjun

    2015-01-01

    Obesity can cause insulin resistance and type 2 diabetes. Moderate elevations in bilirubin levels have anti-diabetic effects. This study is aimed at determining the mechanisms by which bilirubin treatment reduces obesity and insulin resistance in a diet-induced obesity (DIO) mouse model. DIO mice were treated with bilirubin or vehicle for 14 days. Body weights, plasma glucose, and insulin tolerance tests were performed prior to, immediately, and 7 weeks post-treatment. Serum lipid, leptin, adiponectin, insulin, total and direct bilirubin levels were measured. Expression of factors involved in adipose metabolism including sterol regulatory element-binding protein (SREBP-1), insulin receptor (IR), and PPARγ in liver were measured by RT-PCR and Western blot. Compared to controls, bilirubin-treated mice exhibited reductions in body weight, blood glucose levels, total cholesterol (TC), leptin, total and direct bilirubin, and increases in adiponectin and expression of SREBP-1, IR, and PPARγ mRNA. The improved metabolic control achieved by bilirubin-treated mice was persistent: at two months after treatment termination, bilirubin-treated DIO mice remained insulin sensitive with lower leptin and higher adiponectin levels, together with increased PPARγ expression. These results indicate that bilirubin regulates cholesterol metabolism, adipokines and PPARγ levels, which likely contribute to increased insulin sensitivity and glucose tolerance in DIO mice. PMID:26017184

  9. Bilirubin Increases Insulin Sensitivity by Regulating Cholesterol Metabolism, Adipokines and PPARγ Levels

    PubMed Central

    Liu, Jinfeng; Dong, Huansheng; Zhang, Yong; Cao, Mingjun; Song, Lili; Pan, Qingjie; Bulmer, Andrew; Adams, David B.; Dong, Xiao; Wang, Hongjun

    2015-01-01

    Obesity can cause insulin resistance and type 2 diabetes. Moderate elevations in bilirubin levels have anti-diabetic effects. This study is aimed at determining the mechanisms by which bilirubin treatment reduces obesity and insulin resistance in a diet-induced obesity (DIO) mouse model. DIO mice were treated with bilirubin or vehicle for 14 days. Body weights, plasma glucose, and insulin tolerance tests were performed prior to, immediately, and 7 weeks post-treatment. Serum lipid, leptin, adiponectin, insulin, total and direct bilirubin levels were measured. Expression of factors involved in adipose metabolism including sterol regulatory element-binding protein (SREBP-1), insulin receptor (IR), and PPARγ in liver were measured by RT-PCR and Western blot. Compared to controls, bilirubin-treated mice exhibited reductions in body weight, blood glucose levels, total cholesterol (TC), leptin, total and direct bilirubin, and increases in adiponectin and expression of SREBP-1, IR, and PPARγ mRNA. The improved metabolic control achieved by bilirubin-treated mice was persistent: at two months after treatment termination, bilirubin-treated DIO mice remained insulin sensitive with lower leptin and higher adiponectin levels, together with increased PPARγ expression. These results indicate that bilirubin regulates cholesterol metabolism, adipokines and PPARγ levels, which likely contribute to increased insulin sensitivity and glucose tolerance in DIO mice. PMID:26017184

  10. Short communication: artificial ultraviolet B light exposure increases vitamin D levels in cow plasma and milk.

    PubMed

    Jakobsen, Jette; Jensen, Søren Krogh; Hymøller, Lone; Andersen, Elisabeth Wreford; Kaas, Poul; Burild, Anders; Jäpelt, Rie Bak

    2015-09-01

    The number of dairy cows without access to pasture or sunlight is increasing; therefore, the content of vitamin D in dairy products is decreasing. Ultimately, declining vitamin D levels in dairy products will mean that dairy products are a negligible source of natural vitamin D for humans. We tested the ability of a specially designed UVB lamp to enhance the vitamin D3 content in milk from dairy cows housed indoors. This study included 16 cows divided into 4 groups. Each group was exposed daily to artificial UVB light simulating 1, 2, 3, or 4 h of summer sun at 56°N for 24 d, and the group with simulated exposure to 2 h of summer sun daily continued to be monitored for 73 d. We found a significant increase in 25-hydroxyvitamin D3 (25OHD3) levels in plasma as well as vitamin D3 and 25OHD3 levels in milk after daily exposure for 24 d in all treatment groups. Extending daily exposure to artificial UVB light to 73 d did not lead to an increase of vitamin D3 or 25OHD3 level in the milk. In conclusion, the change in production facilities for dairy cows providing cows with no access to pasture and sunlight causes a decrease of vitamin D levels in dairy products. This decrease may be prevented by exposing cows to artificial UVB light in the stable. PMID:26117346

  11. Short communication: artificial ultraviolet B light exposure increases vitamin D levels in cow plasma and milk.

    PubMed

    Jakobsen, Jette; Jensen, Søren Krogh; Hymøller, Lone; Andersen, Elisabeth Wreford; Kaas, Poul; Burild, Anders; Jäpelt, Rie Bak

    2015-09-01

    The number of dairy cows without access to pasture or sunlight is increasing; therefore, the content of vitamin D in dairy products is decreasing. Ultimately, declining vitamin D levels in dairy products will mean that dairy products are a negligible source of natural vitamin D for humans. We tested the ability of a specially designed UVB lamp to enhance the vitamin D3 content in milk from dairy cows housed indoors. This study included 16 cows divided into 4 groups. Each group was exposed daily to artificial UVB light simulating 1, 2, 3, or 4 h of summer sun at 56°N for 24 d, and the group with simulated exposure to 2 h of summer sun daily continued to be monitored for 73 d. We found a significant increase in 25-hydroxyvitamin D3 (25OHD3) levels in plasma as well as vitamin D3 and 25OHD3 levels in milk after daily exposure for 24 d in all treatment groups. Extending daily exposure to artificial UVB light to 73 d did not lead to an increase of vitamin D3 or 25OHD3 level in the milk. In conclusion, the change in production facilities for dairy cows providing cows with no access to pasture and sunlight causes a decrease of vitamin D levels in dairy products. This decrease may be prevented by exposing cows to artificial UVB light in the stable.

  12. Increased serum brain-derived neurotrophic factor (BDNF) levels in patients with narcolepsy.

    PubMed

    Klein, Anders B; Jennum, Poul; Knudsen, Stine; Gammeltoft, Steen; Mikkelsen, Jens D

    2013-06-01

    Narcolepsy is a lifelong sleep disorder characterized by excessive daytime sleepiness, sudden loss of muscle tone (cataplexy), fragmentation of nocturnal sleep and sleep paralysis. The symptoms of the disease strongly correlate with a reduction in hypocretin levels in CSF and a reduction in hypocretin neurons in hypothalamus in post-mortem tissue. Brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) are important for activity-dependent neuronal function and synaptic modulation and it is considered that these mechanisms are important in sleep regulation. We hypothesized that serum levels of these factors are altered in patients with narcolepsy compared to healthy controls without sleep disturbances. Polysomnography data was obtained and serum BDNF and NGF levels measured using ELISA, while hypocretin was measured using RIA. Serum BDNF levels were significantly higher in narcolepsy patients than in healthy controls (64.2±3.9 ng/ml vs. 47.3±2.6 ng/ml, P<0.01), while there were no significant differences in NGF levels. As expected, narcolepsy patients had higher BMI compared to controls, but BMI did not correlate with the serum BDNF levels. The change in BDNF levels was not related to disease duration and sleep parameters did not correlate with BDNF in narcolepsy patients. The mechanisms behind the marked increase in BDNF levels in narcolepsy patients remain unknown. PMID:23570723

  13. Increased circulating urocortin-3 levels is associated with polycystic ovary syndrome.

    PubMed

    Temur, Muzaffer; Yilmaz, Özgür; Aksun, Saliha; Özün Özbay, Pelin; Calan, Mehmet; Küme, Tuncay; Karakulak, Murat; Korkmaz, Hüseyin Anıl

    2016-01-01

    This study was aimed to compare serum urocortin-3 (UCN3) levels in women with polycystic ovary syndrome (PCOS) and healthy women, and establish what role UCN3 levels play in PCOS. Fifty-two patients with PCOS and 55 healthy women were included in the study, matched for age and body mass index. Fasting blood glucose (FBG), insulin, hs-CRP, UCN3 and free-testosterone levels of the all participants were measured. HOMA-IR was used to calculate the insulin resistance. Circulating UCN3 levels were significantly increased in women with PCOS than in control subjects (54.49 ± 5.77 versus 51.28 ± 5.86 pmol/l, p = 0.005). Serum insulin, hs-CRP and HOMA-IR levels were higher in women with PCOS than in control group. UCN3 levels positively correlated with hs-CRP in PCOS group (r = 0.391, p = 0.004). Receiver operating characteristic (ROC) curve analysis showed that the area under the ROC curves were 0.732 (95% CI 0.634-0.830, p < 0.001) for UCN3 levels. The optimal cut-off value of UCN3 for detecting PCOS was ≥51.46 pmol/l, at which the sensitivity was 75% and specificity was 68%. Our results suggest that there is a potential link between PCOS and UCN3 levels. The results of this study support the presence of increased UCN3 levels for the association of inflammation with PCOS. PMID:26488073

  14. Increasing the Comfort Level of Teachers Toward Inclusion Through Use of School Focus Groups

    ERIC Educational Resources Information Center

    Smith, Beth Ann

    2007-01-01

    The purpose of this study was to increase the comfort level of teachers toward inclusion of students with learning, behavioral, and physical disabilities in general-education classrooms for one high school. Participants included 3 focus groups of teachers with 2 groups consisting of 6 teachers and 1 group consisting of 7 teachers. One…

  15. Increased cancer cell proliferation in prostate cancer patients with high levels of serum folate

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Introduction: A recent clinical trial revealed that folic acid supplementation is associated with an increased incidence of prostate cancer (1). The present study evaluates serum and prostate tissue folate levels in men with prostate cancer, compared to histologically normal prostate glands from can...

  16. Record-breaking ozone losses matched by record increase in ultraviolet radiation levels

    SciTech Connect

    Not Available

    1993-12-01

    For the fourth consecutive austral spring, the antarctic ozone hole broke existing records for decrease levels of ozone abundance. This article discusses the possible explainations including unusually low temperatures of the polar vortex, which may enhance ozone loss. UV increases at South Pole, McMurdo, and Palmer Stations were also discussed in conjunction with the Ozone hole.

  17. Reactive electrospinning and biodegradation of cross-linked methacrylated polycarbonate nanofibers.

    PubMed

    Wu, Ruizhi; Zhang, Jian-Feng; Fan, Yuwei; Stoute, Diana; Lallier, Thomas; Xu, Xiaoming

    2011-06-01

    The objectives of this study were to fabricate cross-linked biodegradable polycarbonate nanofibers and to investigate their biodegradability by different enzymes. Poly(2,3-dihydroxycarbonate) was synthesized from naturally occurring l-tartaric acid. The hydroxyl groups on the functional polycarbonate were converted to methacrylate groups to enable the polymer to cross-link under UV irradiation. Smooth cross-linked methacrylated polycarbonate nanofibers (300-1800 nm) were fabricated by a reactive electrospinning process with in situ UV radiation from a mixed solution of linear methacrylated polycarbonate (MPC) and poly(ethylene oxide) (PEO) (MPC:PEO = 9:1) in methanol/chloroform (50/50). These cross-linked nanofibers have shown excellent solvent resistance and their solubility decreases with increasing degree of cross-linking. The thermal properties of linear and cross-linked polycarbonate nanofibers were investigated by differential scanning calorimetry and thermogravimetric analysis. The cross-linked polycarbonate nanofibers show no melting point below 200 °C and their decomposition temperature increases with increasing cross-linking degree. Their biodegradation products by five different enzymes were analyzed using liquid chromatography-mass spectrometry (LC-MS). The biodegradability of the polycarbonate nanofibers decreases with increasing cross-linking degree. These nanofibers were found to support human fibroblast survival and to promote cell attachment. This study demonstrates that cross-linked biodegradable polycarbonate nanofibers with different chemical properties and biodegradability can be fabricated using the novel reactive electrospinning technology to meet the needs of different biomedical applications.

  18. Testosterone-induced increase of insulin-like growth factor I levels depends upon normal levels of growth hormone.

    PubMed

    Saggese, G; Cesaretti, G; Franchi, G; Startari, L

    1996-08-01

    Pubertal development is associated with a rise in plasma insulin-like growth factor I (IGF-I) levels that is related both to the increase in sex steroids and/or to the sex steroid-induced augmentation in endogenous growth hormone (GH) secretion. In order to investigate the relationship between IGF-I, GH and testosterone, we examined 42 male subjects with various clinical conditions (classical GH deficiency (CGHD, N = 5), non-classical GH deficiency (NCGHD, N = 7), short idiopathic stature (N = 6), nutritional obesity (N = 8), GH-treated CGHD (N = 4), GH-treated NCGHD (N = 5) and normal stature (N = 7)) in which , for evaluation of hypogonadism (i.e. the absence of one or both testes from the scrotal sac), human chorionic gonadotropin (hCG) tests were performed. We measured IGF-I, total and free testosterone and dehydroepiandrosterone sulfate (DHEAS) by radioimmunoassays before and 48 and 96 h after the start of the test. The values of IGF-I were lower (0.001 < p < 0.005) in CGHD and NCGHD than in the other groups. In comparison to basal levels, IGF-I values increased (0.005 < p < 0.05) both 48 and 96 h after the start of the hCG test in short idiopathic and normal stature children and in GH-treated subjects with NCGHD, but only 96 h in subjects with untreated NCGHD and GH-treated CGHD. No difference was demonstrated in basal values of total testosterone among any of the groups, while basal free testosterone levels were higher (0.001 < p < 0.05) in GH-treated subjects with NCGHD than in all the other groups except nutritional obesity; furthermore, free testosterone was higher (p < 0.05) in nutritional obesity than in CGHD. The values of total and free testosterone obtained both 48 and 96 h after the start of the hCG test were higher (0.001 < p < 0.05) than basal values in all groups. The DHEAS values did not show any significant change during the hCG test. Basal values were higher (0.01 < p < 0.05) in nutritional obesity than in the other groups. Considering all

  19. High level increase in liver enzymes and severe thrombocytopenia in a male case of anorexia nervosa*

    PubMed Central

    Karahmadi, Mojgan; Layegh, Elmira; Layegh, Samira; Keypour, Maryam

    2011-01-01

    BACKGROUND: Anorexia nervosa (AN) is a difficult-to-treat psychosomatic disease. Very few cases of acute liver failure associated with AN have been described. We describe one patient who was affected by AN and presented high level increase of serum liver enzymes, along with sever thrombocytopenia. Then, we discuss the possible etiopathogenic factors. METHODS: A 14-year-old boy with AN was admitted in the pediatric psychiatric emergency department of Alzahra Hospital with impaired electrolyte levels, bradycardia, hypotension, liver dysfunction, and thrombocytopenia. RESULTS: A ten-time increase in liver enzymes and thrombocytopenia were observed on admission. After two months of treatment, the levels were within the normal range. CONCLUSIONS: Improvement of initial clinical symptoms and recovery of liver enzymes and thrombocytopenia after the treatment suggested that liver dysfunction and thrombocytopenia may be observed in AN patients and should be taken care of by physicians. PMID:22973335

  20. Global increasing of mean sea level and erroneous treatment of a role of thermal factors

    NASA Astrophysics Data System (ADS)

    Barkin, Yu. V.

    2009-04-01

    Satellite methods of studies of the ocean surface - methods of altimetry - have been obtained intensive development in the last decades (since 1993). However, altimetry studies with the help of special satellites such as TOPEX-Poseidon not only have not cleared up understanding of the phenomenon of increase of sea level (SLR), but have even more confused and without that a complex question on the reasons of increase of sea level. Appeared, that classical determinations of average velocity of increase of sea level on coastal observations (1.4-1.7 mm / yr) approximately for 0.8-1.0 mm / yr it is less, rather than by modern satellite determinations of satellites TOPEX - Poseidon etc. (2.5 - 2.8 mm / yr). On the basis of the data of altimetry observations of TOPEX-Poseidon and Jason for the period 1993-2003 for geocentric velocity of increase of sea level (of global ocean) the value 2.8+/-0.4 mm / yr [1] has been obtained. In the given report the full answer is actually is given to a question put by leading experts on research of the sea level: "The TOPEX/Poseidon and Jason satellite altimeter missions provided a 12 year record of sea level change, which show increase of global mean sea level of 2.8+/-0.4 mm/yr, with considerable geographic variation. An important question for climate studies is to determine the cause of this change - specifically how much of the change is due to steric (heating) versus eustatic (runoff, melting ice, etc.) contribution?" [1]. There is, a big value of average velocity of increase of the sea level on the satellite data, it is possible to explain only by kinematical effect in data of observations. The motion of the satellite "is concerned" to the centre of mass of our planet, and its position is determined by a geocentric radius - vector. Therefore northern drift of the centre of mass in the Earth body [2] as though results in reduction of distances from the satellite up to the sea surface in the southern hemisphere and to their reduction

  1. Cytotoxic evaluation of biomechanically improved crosslinked ovine collagen on human dermal fibroblasts.

    PubMed

    Awang, M A; Firdaus, M A B; Busra, M B; Chowdhury, S R; Fadilah, N R; Wan Hamirul, W K; Reusmaazran, M Y; Aminuddin, M Y; Ruszymah, B H I

    2014-01-01

    Earlier studies in our laboratory demonstrated that collagen extracted from ovine tendon is biocompatible towards human dermal fibroblast. To be able to use this collagen as a scaffold in skin tissue engineering, a mechanically stronger scaffold is required that can withstand manipulation before transplantation. This study was conducted to improve the mechanical strength of this collagen sponge using chemical crosslinkers, and evaluate their effect on physical, chemical and biocompatible properties. Collagen sponge was crosslinked with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) and glutaraldehyde (GA). Tensile test, FTIR study and mercury porosimetry were used to evaluate mechanical properties, chemical property and porosity, respectively. MTT assay was performed to evaluate the cytotoxic effect of crosslinked collagen sponge on human dermal fibroblasts. The FTIR study confirmed the successful crosslinking of collagen sponge. Crosslinking with EDC and GA significantly increased the mechanical strength of collagen sponge, with GA being more superior. Crosslinking of collagen sponge significantly reduced the porosity and the effect was predominant in GA-crosslinked collagen sponge. The GA-crosslinked collagen showed significantly lower, 60% cell viability towards human dermal fibroblasts compared to that of EDC-crosslinked collagen, 80% and non-crosslinked collagen, 100%. Although the mechanical strength was better when using GA but the more toxic effect on dermal fibroblast makes EDC a more suitable crosslinker for future skin tissue engineering.

  2. INCREASES IN CYTOSOLIC CALCIUM ION LEVELS IN HUMAN NATURAL KILLER CELLS IN RESPONSE TO BUTYLTIN EXPOSURE

    PubMed Central

    Lane, Rhonda; Ghazi, Sabah O.; Whalen, Margaret M.

    2009-01-01

    This study investigated whether exposures to butyltins (BTs), tributylin (TBT) and dibutyltin (DBT) were able to alter cytosolic calcium levels in human natural killer (NK) cells. Additionally, the effects of cytosolic calcium ion increases on the activation state of mitogen activated protein kinases (MAPKs) in NK cells were also investigated. NK cells are an intital immune defense against the development of tumors or viral infections. TBT and DBT are widespread environmental contaminants, due to their various industrial applications. Both TBT and DBT have been shown to decrease the ability of NK cells to lyse tumor cells (lytic function). TBT has also been shown to activate MAPKs in NK cells. The results of this study indicated that TBT increased cytosolic calcium levels by as much as 100% after a 60 min exposure to 500 nM TBT while DBT increased cytosolic calcium levels to a much smaller extent (and required higher concentrations). The results also indicated that increases in cytosolic calcium could activate MAPKs but only for a short period of time (5 min), while previous studies showed that activation of MAPKs by TBT last for at least 6 hours. Thus, it appears that TBT stimulated increases in cytosolic calcium may contribute to, but are not fully responsible for, TBT-induced activation of MAPKs. PMID:19365649

  3. Superpredation increases mercury levels in a generalist top predator, the eagle owl.

    PubMed

    Lourenço, Rui; Tavares, Paula C; del Mar Delgado, Maria; Rabaça, João E; Penteriani, Vincenzo

    2011-06-01

    Superpredation can increase the length of the food chain and potentially lead to mercury (Hg) bioaccumulation in top predators. We analysed the relationship of Hg concentrations in eagle owls Bubo bubo to diet composition and the percentage of mesopredators in the diet. Hg levels were measured in the adult feathers of eagle owls from 33 owl territories in the south-western Iberian Peninsula, and in three trophic levels of their prey: primary consumers, secondary consumers and mesopredators. In addition, we studied 6,181 prey in the eagle owl diet. Hg concentrations increased along the food chain, but the concentrations in eagle owls showed considerable variation. The Hg concentration in eagle owls increased when the percentage of mesopredators in the diet increased and the percentage of primary consumers decreased. Superpredation is often related to food stress, and the associated increase in accumulation of Hg may cause additional negative effects on vertebrate top predators. Hg levels in these eagle owl populations are relatively low, but future monitoring is recommended. PMID:21298339

  4. Increased levels of ambient fungal spores in Taiwan are associated with dust events from China

    NASA Astrophysics Data System (ADS)

    Wu, Pei-Chih; Tsai, Jui-Chen; Li, Fang-Chun; Lung, Shih-Chun; Su, Huey-Jen

    2004-09-01

    Fungi are ubiquitous in nature and their spores are often dispersed into the atmosphere through turbulent airstreams. As yellow sandstorm blown from deserts in China had affected the ambient air quality with increasing levels of ambient particulates, often including significant amounts of biologically active particles has therefore become imperative for concerns of their health implications. Our study was aimed to examine the effects of yellow sandstorm events on the fungal composition and concentrations in ambient air. Atmospheric fungal spores were continuously collected using Burkard Volumetric Spore Trap. Samples collected between December 2000 and April 2001 were selected for priority analysis from days when the yellow sandstorms were reported to affect Taiwan according to the Central Weather Bureau in Taiwan. The composition of dominant spores such as Basidiospore, Penicillium/Aspergillus, Nigrospora, Arthrinium, Curvularia, Rusts, Stemphylium, Cercospora, Pithomyces, and unidentified fungi were significantly higher than those of background days. The increase of Basidiospore, Penicillium/Aspergillus, Nigrospora, and those unidentified fungi seems to be significantly associated with the increase of ambient particulate levels with regression coefficients ranging from 0.887 to 31.98. Our study has identified increasing ambient concentrations during sandstorm episodes are observed for some major fungi, Basidiospore, Penicillium, Aspergillus, and those unidentified fungi and the trends of the increase seems to associate with ambient particulate levels. Further efforts to clarify the relationship between those high fungal spore exposures and clinical adverse health effects are suggested in the future. In addition, effects of climatic factors and other particulate levels on the variation of ambient fungal spore levels are also desired in further study. Additional monitoring of ambient fungal spores in the first line of west coastline is hoped to assist in

  5. Exercise increases serum endostatin levels in female and male patients with diabetes and controls

    PubMed Central

    2014-01-01

    Background Type 2 diabetes mellitus (T2DM) is often associated with atherosclerotic changes in coronary vessels, most notably plaques. The angiostatic parameter endostatin is able to inhibit angiogenesis in tissue as well as in plaques and therefore plays an important role in physiological and pathological neovascularisation. The aim of the present study was to investigate sex-specific differences and the influence of exercise on circulating endostatin levels in patients suffering from diabetes, and control subjects. Methods In total, 42 T2DM-patients and 45 control subjects were investigated. They underwent a graded physical stress test (ergometry). Serum endostatin levels were measured in venous blood at rest and directly after reaching maximum workload. Results Females showed significantly higher endostatin levels at baseline measurements compared to men, independently of their underlying disease. In both female and male T2DM-patients endostatin levels were significantly lower compared to controls. Both groups and sexes showed a significant increase of endostatin after physical stress, whereas the extent of endostatin-increase was between 10.59-15.05%. Conclusion Middle-aged healthy female individuals as well as female T2DM-patients showed higher circulating serum endostatin levels compared to males, suggesting a hormonal influence on baseline circulating endostatin amounts. Exercise-induced increase in endostatin is also observable in patients suffering from T2DM. Concerning vascularisation, lower endostatin levels in T2DM might be advantageous. Concerning plaque stability, lower levels might be prejudicial. Trial registration Clinical Trial Registration-URL: http://clinicaltrials.gov/ct2/results?term=NCT01165515 PMID:24393402

  6. Increased levels of carbonic anhydrase II in the developing Down syndrome brain.

    PubMed

    Palminiello, Sonia; Kida, Elizabeth; Kaur, Kulbir; Walus, Marius; Wisniewski, Krystyna E; Wierzba-Bobrowicz, Teresa; Rabe, Ausma; Albertini, Giorgio; Golabek, Adam A

    2008-01-23

    By using a proteomic approach, we found increased levels of carbonic anhydrase II (CA II) in the brain of Ts65Dn mice, a mouse model for Down syndrome (DS). Further immunoblot analyses showed that the levels of CA II are increased not only in the brain of adult Ts65Dn mice but also in the brain of infants and young children with DS. Cellular localization of the enzyme in human brain, predominantly in the oligodendroglia and primitive vessels in fetal brain and in the oligodendroglia and some GABAergic neurons postnatally, was similar in DS subjects and controls. Given the role of CA II in regulation of electrolyte and water balance and pH homeostasis, up-regulation of CA II may reflect a compensatory mechanism mobilized in response to structural/functional abnormalities in the developing DS brain. However, this up-regulation may also have an unfavorable effect by increasing susceptibility to seizures of children with DS.

  7. [Effect of the increasing levels of soil radioactive pollution on the biochemical composition of plants].

    PubMed

    Gromova, V S; Pchelenok, O A; Kozlova, N M

    2012-01-01

    The study was undertaken to study a relationship between the changes of some parameters of the biochemical and mineral composition of different plants, such as rape, pods, and lentil, and the levels of soil radiation pollution, by using the conventional methods. Radioactive pollution of dark-grey forest soils was found to cause a change in the biochemical composition of plant seeds even at the level of cesium 137 (137Cs) within the present temporary permissible levels (TPL) (600 Bq/kg): there were elevated concentrations of salts of potassium, phosphorus, ammonia nitrogen, catechols, sucrose, and some amino acids. With the radioactive cesium level exceeding the TPL, biochemical changes in the seeds depended on the species of the plants: in the rape seeds, the additional formation of sucrose and amino acids continued, but less intensively than with its lower radiation; the pod beans were significantly positively correlated with the increasing amounts of catechols.

  8. [Effect of the increasing levels of soil radioactive pollution on the biochemical composition of plants].

    PubMed

    Gromova, V S; Pchelenok, O A; Kozlova, N M

    2012-01-01

    The study was undertaken to study a relationship between the changes of some parameters of the biochemical and mineral composition of different plants, such as rape, pods, and lentil, and the levels of soil radiation pollution, by using the conventional methods. Radioactive pollution of dark-grey forest soils was found to cause a change in the biochemical composition of plant seeds even at the level of cesium 137 (137Cs) within the present temporary permissible levels (TPL) (600 Bq/kg): there were elevated concentrations of salts of potassium, phosphorus, ammonia nitrogen, catechols, sucrose, and some amino acids. With the radioactive cesium level exceeding the TPL, biochemical changes in the seeds depended on the species of the plants: in the rape seeds, the additional formation of sucrose and amino acids continued, but less intensively than with its lower radiation; the pod beans were significantly positively correlated with the increasing amounts of catechols. PMID:22834257

  9. Rosiglitazone improves insulin sensitivity with increased serum leptin levels in patients with type 2 diabetes mellitus.

    PubMed

    Kim, Hae Jin; Kim, Soo Kyung; Shim, Wan Sub; Lee, Jae Hyuk; Hur, Kyu Yeon; Kang, Eun Seok; Ahn, Chul Woo; Lim, Sung Kil; Lee, Hyun Chul; Cha, Bong Soo

    2008-07-01

    Rosiglitazone (RSG) is known to be an agonist for the peroxisome proliferator-activated receptor-gamma (PPARgamma) and promotes differentiation of pre-adipocytes into adipocytes. Leptin is highly correlated with adiposity, while the activation of PPARgamma is known to inhibit Lep gene expression and leptin release. This study was performed to evaluate the relationship between changes in circulating leptin levels, insulin sensitivity and regional adiposity after RSG treatment. Two hundred fifty-one type 2 diabetic patients (176 men and 75 women) who had been treated with sulfonylurea and/or metformin received 4 mg of RSG daily, in addition to the previous medications. Before and after RSG treatment (average duration 5.6+/-0.9 months), indices of insulin resistance, metabolic parameters, and serum leptin and adiponectin levels were measured. Abdominal subcutaneous fat thickness (SFT(max)) and visceral fat thickness were measured by sonography. After RSG treatment, HOMA-IR index decreased significantly (2.82+/-1.94 vs. 2.01+/-1.58), while BMI and SFT(max) increased, and leptin (4.72+/-3.77 vs. 5.69+/-4.30 ng/ml) and adiponectin levels (7.54+/-10.20 vs. 12.89+/-10.13 microg/ml) increased. The increase in serum leptin correlated with an increase in SFT(max) (r=0.511, p<0.001) and with a reduction in HOMA-IR (r=-0.368, p<0.001). The correlation of Delta leptin with Delta HOMA-IR and with Delta SFT(max) was higher in females and among insulin-resistant subjects. In conclusion, RSG improves the insulin sensitivity with increased serum leptin levels in patients with type 2 diabetes mellitus, which is related to an increase in subcutaneous adiposity.

  10. Increased plasma neopterin and hs-CRP levels in patients with endemic fluorosis.

    PubMed

    Varol, Ercan; Aksoy, Fatih; Icli, Atilla; Arslan, Akif; Yuksel, Ozlem; Ersoy, I Hakki; Varol, Simge; Dogan, Abdullah

    2012-11-01

    Although fluoride induced inflammatory reactions have been shown in animals and in vitro humans, there are few studies about fluoride induced inflammatory reactions in human beings at clinical setting. We aimed to measure the plasma neopterin, a marker of activation of the monocyte/macrophage system, and high sensitivity C-reactive protein (hs-CRP) levels in patients with endemic fluorosis to investigate the possible role of inflammatory processes (monocyte/macrophage activity) in the underlying pathophysiology of fluoride toxicity at clinical level. Plasma neopterin and hs-CRP levels were determined in endemic fluorosis patients and control subjects. Plasma neopterin levels were significantly higher among patients with endemic fluorosis when compared with control group (2.40 ± 0.66 vs. 1.63 ± 0.27 ng/mL respectively; p < 0.001) and plasma hs-CRP levels were also significantly higher among patients with endemic fluorosis when compared with control group (2.41 ± 1.23 vs. 1.93 ± 0.64 mg/L respectively; p < 0.001). Plasma neopterin levels were positively correlated with urine fluoride levels (r = 0.67, p < 0.001) and serum hs-CRP levels were positively correlated with urine fluoride levels (r = 0.36, p < 0.001). We have found that plasma neopterin and hs-CRP levels are increased in patients with endemic fluorosis. We have concluded that inflammation play an important role in the pathophysiology of fluoride toxicity in patients with endemic fluorosis.

  11. Increased serum levels of apoptosis in deficit syndrome schizophrenia patients: a preliminary study

    PubMed Central

    Beyazyüz, Murat; Küfeciler, Tarkan; Bulut, Leyla; Ünsal, Cüneyt; Albayrak, Yakup; Akyol, Esra Soydaş; Baykal, Saliha; Kuloglu, Murat; Hashimoto, Kenji

    2016-01-01

    Background Schizophrenia is a chronic and debilitating disorder, the etiology of which remains unclear. Apoptosis is a programmed cell death mechanism that might be implicated in neuropsychiatric disorders, including schizophrenia. In this study, we aimed to compare the serum levels of apoptosis among deficit schizophrenia (DS) syndrome patients, nondeficit schizophrenia (NDS) patients, and healthy controls (HCs). Patients and methods After the inclusion and exclusion criteria were applied, 23 DS patients, 46 NDS patients, and 33 HCs were included in the study. The serum apoptosis levels were measured using a quantitative sandwich enzyme immunoassay with human monoclonal antibodies directed against DNA and histones. Results There was a significant difference among the three groups in terms of the levels of apoptosis (F2,96=16.58; P<0.001). The serum apoptosis levels in the DS and NDS groups were significantly higher than those in the HC group. Furthermore, the serum apoptosis levels in the DS group were significantly higher than the levels in the NDS group. Conclusion This study suggests that increased levels of apoptosis may be implicated in the pathophysiology of DS syndrome. However, further studies are needed to support the role of apoptosis in DS. PMID:27307738

  12. Methodology for Prototyping Increased Levels of Automation for Spacecraft Rendezvous Functions

    NASA Technical Reports Server (NTRS)

    Hart, Jeremy J.; Valasek, John

    2007-01-01

    The Crew Exploration Vehicle necessitates higher levels of automation than previous NASA vehicles, due to program requirements for automation, including Automated Rendezvous and Docking. Studies of spacecraft development often point to the locus of decision-making authority between humans and computers (i.e. automation) as a prime driver for cost, safety, and mission success. Therefore, a critical component in the Crew Exploration Vehicle development is the determination of the correct level of automation. To identify the appropriate levels of automation and autonomy to design into a human space flight vehicle, NASA has created the Function-specific Level of Autonomy and Automation Tool. This paper develops a methodology for prototyping increased levels of automation for spacecraft rendezvous functions. This methodology is used to evaluate the accuracy of the Function-specific Level of Autonomy and Automation Tool specified levels of automation, via prototyping. Spacecraft rendezvous planning tasks are selected and then prototyped in Matlab using Fuzzy Logic techniques and existing Space Shuttle rendezvous trajectory algorithms.

  13. The colibactin warhead crosslinks DNA

    NASA Astrophysics Data System (ADS)

    Vizcaino, Maria I.; Crawford, Jason M.

    2015-05-01

    Members of the human microbiota are increasingly being correlated to human health and disease states, but the majority of the underlying microbial metabolites that regulate host-microbe interactions remain largely unexplored. Select strains of Escherichia coli present in the human colon have been linked to the initiation of inflammation-induced colorectal cancer through an unknown small-molecule-mediated process. The responsible non-ribosomal peptide-polyketide hybrid pathway encodes ‘colibactin’, which belongs to a largely uncharacterized family of small molecules. Genotoxic small molecules from this pathway that are capable of initiating cancer formation have remained elusive due to their high instability. Guided by metabolomic analyses, here we employ a combination of NMR spectroscopy and bioinformatics-guided isotopic labelling studies to characterize the colibactin warhead, an unprecedented substituted spirobicyclic structure. The warhead crosslinks duplex DNA in vitro, providing direct experimental evidence for colibactin's DNA-damaging activity. The data support unexpected models for both colibactin biosynthesis and its mode of action.

  14. A cost for high levels of sperm competition in rodents: increased sperm DNA fragmentation.

    PubMed

    delBarco-Trillo, Javier; García-Álvarez, Olga; Soler, Ana Josefa; Tourmente, Maximiliano; Garde, José Julián; Roldan, Eduardo R S

    2016-03-16

    Sperm competition, a prevalent evolutionary process in which the spermatozoa of two or more males compete for the fertilization of the same ovum, leads to morphological and physiological adaptations, including increases in energetic metabolism that may serve to propel sperm faster but that may have negative effects on DNA integrity. Sperm DNA damage is associated with reduced rates of fertilization, embryo and fetal loss, offspring mortality, and mutations leading to genetic disease. We tested whether high levels of sperm competition affect sperm DNA integrity. We evaluated sperm DNA integrity in 18 species of rodents that differ in their levels of sperm competition using the sperm chromatin structure assay. DNA integrity was assessed upon sperm collection, in response to incubation under capacitating or non-capacitating conditions, and after exposure to physical and chemical stressors. Sperm DNA was very resistant to physical and chemical stressors, whereas incubation in non-capacitating and capacitating conditions resulted in only a small increase in sperm DNA damage. Importantly, levels of sperm competition were positively associated with sperm DNA fragmentation across rodent species. This is the first evidence showing that high levels of sperm competition lead to an important cost in the form of increased sperm DNA damage.

  15. Increased Cord Blood Betatrophin Levels in the Offspring of Mothers with Gestational Diabetes

    PubMed Central

    Wu, Shimin; Zhao, Yue; Du, Caiqi; Yuan, Guandou; Ning, Qin; McCormick, Kenneth; Luo, Xiaoping

    2016-01-01

    Aim Exposing a fetus to hyperglycemia can increase the risk for later-life metabolic disorders. Betatrophin has been proposed as a key regulator of pancreatic beta cell proliferation and lipid regulation. Highly responsive to nutritional signals, serum betatrophin concentrations have been found to be altered by various physiological and pathological conditions. We hypothesized that betatrophin levels are increased in the cord blood in offspring exposed to intrauterine hyperglycemia. Methods This was a cross-sectional study including 54 mothers who underwent uncomplicated Cesarean delivery in a university hospital. Maternal gestational glucose concentration was determined at 24–48 weeks gestation after a 75-g OGTT. Cord blood and placental tissue was collected immediately post delivery. Metabolic parameters were determined in the Clinical Laboratory. Cord blood betatrophin levels were assayed using a commercially available ELISA kit. Placental mitochondrial content was determined by real-time PCR. Results Cord blood betatrophin levels were increased in the gestational diabetes mellitus (GDM) group compared with the normoglycemic group. Furthermore, betatrophin levels were positively correlated with maternal gestational 2h post-OGTT glucose, cord blood insulin, HOMA-IR, and inversely correlated with placental mitochondrial content. Conclusions Cord blood betatrophin may function as a potential biomarker of maternal intrauterine hyperglycemia and fetal insulin resistance, which may presage for long-term metabolic impact of GDM on offspring. PMID:27196053

  16. Mothers Do Not Show Increased Offspring Avoidance and Elevated Corticosterone Levels during Weaning Conflict in Rats

    PubMed Central

    Cox, Charlotte; Hager, Reinmar

    2016-01-01

    Parent-offspring conflict is predicted to occur because offspring will demand more parental investment than is optimal for the parent, and is said to be strongest during weaning when parents reduce nursing while offspring continue to demand parental care. While weaning conflict has been shown to be stressful in offspring, little is known about the effects of weaning conflict on mothers. We hypothesized that during weaning mothers have higher levels of stress hormone (corticosterone) compared to early lactation because of increased offspring demand. Further, we predicted that if mothers are given the option to avoid offspring solicitation they would do so and show lower corticosterone levels. We tested our hypotheses in an experimental population of rats in which one group of females was given the opportunity to avoid offspring solicitation. We measured faecal corticosterone metabolite levels using a non-invasive approach, and maternal and offspring behaviours during weaning. In contrast to our predictions, we detected lower levels of corticosterone metabolites during weaning than before, irrespective of cage type. Further, during weaning mothers did not show increased offspring avoidance behaviour although offspring solicitation increased significantly. Our results therefore cast doubt on the generally accepted notion of weaning conflict as a stressful period for mothers characterized by overt offspring solicitation. PMID:27662366

  17. Glucose deprivation increases hydrogen peroxide level in immunostimulated rat primary astrocytes.

    PubMed

    Choi, Ji Woong; Shin, Chan Young; Yoo, Byoung Kwon; Choi, Min Sik; Lee, Woo Jong; Han, Byoung Hee; Kim, Won-Ki; Kim, Hyoung-Chun; Ko, Kwang Ho

    2004-03-01

    Activated astrocytes produce a large amount of bioactive molecules, including reactive oxygen and nitrogen species. Astrocytes are in general resistant to those reactive species. However, we previously reported that immunostimulated astrocytes became highly vulnerable to metabolic insults, such as glucose deprivation. In this study, we investigated whether H(2)O(2) production was associated with the increased vulnerability. Glucose deprivation for up to 8 hr did not change the intracellular level of H(2)O(2) in astrocytes. Treatment with lipopolysaccharide plus interferon-gamma for 48 hr evoked astroglial H(2)O(2) production; however, no apparent death or injury was observed in immunostimulated astrocytes. Glucose deprivation after 48 hr of immunostimulation markedly increased H(2)O(2) level, depleted adenosine triphosphate (ATP), and enhanced lactate dehydrogenase (LDH) release. The ATP depletion and LDH release were in part prevented by catalase, mannitol, and N-acetyl-L-cysteine. The enhanced level of H(2)O(2) in glucose-deprived immunostimulated astrocytes appeared to be secondary to the depletion of reduced glutathione. 4-(2-Aminoethyl)bebzenesulfonyl fluoride (AEBSF), an inhibitor of NADPH oxidase, reduced H(2)O(2) level and LDH release in glucose-deprived immunostimulated astrocytes. H(2)O(2), either endogenously produced or exogenously added, depolarized mitochondrial transmembrane potential in glucose-deprived astrocytes, leading to their ATP depletion and death. The present results strongly indicate that glucose deprivation causes deterioration of immunostimulated astrocytes by increasing the intracellular concentration of H(2)O(2).

  18. Elasticity of cross-linked semiflexible biopolymers under tension.

    PubMed

    von der Heydt, Alice; Wilkin, Daniel; Benetatos, Panayotis; Zippelius, Annette

    2013-09-01

    Aiming at the mechanical properties of cross-linked biopolymers, we set up and analyze a model of two weakly bending wormlike chains subjected to a tensile force, with regularly spaced inter-chain bonds (cross-links) represented by harmonic springs. Within this model, we compute the force-extension curve and the differential stiffness exactly and discuss several limiting cases. Cross-links effectively stiffen the chain pair by reducing thermal fluctuations transverse to the force and alignment direction. The extra alignment due to cross-links increases both with growing number and with growing strength of the cross-links, and is most prominent for small force f. For large f, the additional, cross-link-induced extension is subdominant except for the case of linking the chains rigidly and continuously along their contour. In this combined limit, we recover asymptotically the elasticity of a weakly bending wormlike chain without constraints, stiffened by a factor of 4. The increase in differential stiffness can be as large as 100% for small f or large numbers of cross-links.

  19. Intra-spike crosslinking overcomes antibody evasion by HIV-1.

    PubMed

    Galimidi, Rachel P; Klein, Joshua S; Politzer, Maria S; Bai, Shiyu; Seaman, Michael S; Nussenzweig, Michel C; West, Anthony P; Bjorkman, Pamela J

    2015-01-29

    Antibodies developed during HIV-1 infection lose efficacy as the viral spike mutates. We postulated that anti-HIV-1 antibodies primarily bind monovalently because HIV's low spike density impedes bivalent binding through inter-spike crosslinking, and the spike structure prohibits bivalent binding through intra-spike crosslinking. Monovalent binding reduces avidity and potency, thus expanding the range of mutations permitting antibody evasion. To test this idea, we engineered antibody-based molecules capable of bivalent binding through intra-spike crosslinking. We used DNA as a "molecular ruler" to measure intra-epitope distances on virion-bound spikes and construct intra-spike crosslinking molecules. Optimal bivalent reagents exhibited up to 2.5 orders of magnitude increased potency (>100-fold average increases across virus panels) and identified conformational states of virion-bound spikes. The demonstration that intra-spike crosslinking lowers the concentration of antibodies required for neutralization supports the hypothesis that low spike densities facilitate antibody evasion and the use of molecules capable of intra-spike crosslinking for therapy or passive protection. PMID:25635457

  20. Long-term environmental enrichment leads to regional increases in neurotrophin levels in rat brain.

    PubMed

    Ickes, B R; Pham, T M; Sanders, L A; Albeck, D S; Mohammed, A H; Granholm, A C

    2000-07-01

    A number of studies have demonstrated that both morphological and biochemical indices in the brain undergo alterations in response to environmental influences. In previous work we have shown that rats raised in an enriched environmental condition (EC) perform better on a spatial memory task than rats raised in isolated conditions (IC). We have also found that EC rats have a higher density of immunoreactivity than IC rats for both low and high affinity nerve growth factor (NGF) receptors in the basal forebrain. In order to determine if these alterations were coupled with altered levels of neurotrophins in other brain regions as well, we measured neurotrophin levels in rats that were raised in EC or IC conditions. Rats were placed in the different environments at 2 months of age and 12 months later brain regions were dissected and analyzed for NGF, brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) levels using Promega ELISA kits. We found that NGF and BDNF levels were increased in the cerebral cortex, hippocampal formation, basal forebrain, and hindbrain in EC animals compared to age-matched IC animals. NT-3 was found to be increased in the basal forebrain and cerebral cortex of EC animals as well. These findings demonstrate significant alterations in NGF, BDNF, and NT-3 protein levels in several brain regions as a result of an enriched versus an isolated environment and thus provide a possible biochemical basis for behavioral and morphological alterations that have been found to occur with a shifting environmental stimulus.

  1. Sodium Chloride IncreasesLevels by Suppressing Aβ Clearance in Cultured Cells.

    PubMed

    Cheng, Xiao-Juan; Gao, Yuan; Zhao, Yu-Wu; Cheng, Xiao-Dong

    2015-01-01

    Recent studies suggest that high-salt diet is associated with cognitive decline in human and mouse. The fact that genetic factors account for less than 50% cases of sporadic Alzheimer's disease (AD) highlights the important contribution of environmental factors, such as high-salt diet, in AD pathogenesis. However, whether and how high-salt diet fits the "amyloid cascade" hypothesis remains unexplored. Here, we show sodium chloride (NaCl) could increaselevels in the medium of HEK293 cells overexpressing amyloid precursor protein (APP) or C99 fragment. NaCl treatment dose not affect APP level, gamma secretase level or activity. Instead, NaCl treatment suppresses the capacity of cells to clear Aβ and reduces Apolipoprotein E (ApoE) level. Finally, NaCl treated THP-1 or BV2 cells are inefficient in clearing Aβ when co-cultured with rat primary neurons. Our study suggests that high-salt diet may increase AD risk by directly modulating Aβ levels.

  2. Rotational stress-induced increase in epinephrine levels delays cutaneous wound healing in mice.

    PubMed

    Romana-Souza, Bruna; Otranto, Marcela; Vieira, Andreza M; Filgueiras, Cláudio C; Fierro, Iolanda M; Monte-Alto-Costa, Andréa

    2010-03-01

    Stress impairs wound healing of cutaneous lesions; however, the mechanism is still unclear. The aim of this study was to evaluate the effects of rotational stress on cutaneous wound healing in mice and propose a mechanism. Male mice were spun at 45 rpm for 15 min every hour beginning 3 days before wounding until euthanasia. Control animals were not subjected to stress. To confirm that catecholamines participate in stress-induced delay of wound healing, mice were treated daily with propranolol. An excisional lesion was created and measured. Seven and 14 days later, animals were killed and lesions collected. Sections were stained with hematoxylin-eosin and immunostained for alpha-smooth muscle actin and proliferating cell nuclear antigen. Matrix metalloproteinase (MMP)-2 and -9 activity, nitrite levels, and tumor necrosis factor-alpha (TNF-alpha) expression were measured in the wounds. In addition, murine skin fibroblast cultures were treated with high levels of epinephrine and fibroblast activity was evaluated. Stressed mice exhibited reduced locomotor activity and increased normetanephrine plasma levels. Rotational stress was associated with decreased wound contraction, reduced re-epithelialization, reduced MMP-2 and MMP-9 activation, but with strongly increased nitrite levels. Furthermore, inflammatory cell infiltration, TNF-alpha expression, myofibroblastic differentiation, and angiogenesis were all delayed in the stress group. Propranolol administration reversed the deleterious effects of stress on wound contraction and re-epithelialization. High epinephrine concentrations increased murine skin fibroblast proliferation and nitric oxide synthesis, and strongly inhibited skin fibroblast migration and both pro- and active MMP-2. In conclusion, rotational stress impairs cutaneous wound healing due to epinephrine increased levels.

  3. Diffuse radiation increases global ecosystem-level water-use efficiency

    NASA Astrophysics Data System (ADS)

    Moffat, A. M.; Reichstein, M.; Cescatti, A.; Knohl, A.; Zaehle, S.

    2012-12-01

    Current environmental changes lead not only to rising atmospheric CO2 levels and air temperature but also to changes in air pollution and thus the light quality of the solar radiation reaching the land-surface. While rising CO2 levels are thought to enhance photosynthesis and closure of stomata, thus leading to relative water savings, the effect of diffuse radiation on transpiration by plants is less clear. It has been speculated that the stimulation of photosynthesis by increased levels of diffuse light may be counteracted by higher transpiration and consequently water depletion and drought stress. Ultimately, in water co-limited systems, the overall effect of diffuse radiation will depend on the sensitivity of canopy transpiration versus photosynthesis to diffuse light, i.e. whether water-use efficiency changes with relative levels of diffuse light. Our study shows that water-use efficiency increases significantly with higher fractions of diffuse light. It uses the ecosystem-atmosphere gas-exchange observations obtained with the eddy covariance method at 29 flux tower sites. In contrast to previous global studies, the analysis is based directly on measurements of diffuse radiation. Its effect on water-use efficiency was derived by analyzing the multivariate response of carbon and water fluxes to radiation and air humidity using a purely empirical approach based on artificial neural networks. We infer that per unit change of diffuse fraction the water-use efficiency increases up to 40% depending on diffuse fraction levels and ecosystem type. Hence, in regions with increasing diffuse radiation positive effects on primary production are expected even under conditions where water is co-limiting productivity.

  4. Oxidized low density lipoprotein increases RANKL level in human vascular cells. Involvement of oxidative stress

    SciTech Connect

    Mazière, Cécile; Salle, Valéry; Gomila, Cathy; Mazière, Jean-Claude

    2013-10-18

    Highlights: •Oxidized LDL enhances RANKL level in human smooth muscle cells. •The effect of OxLDL is mediated by the transcription factor NFAT. •UVA, H{sub 2}O{sub 2} and buthionine sulfoximine also increase RANKL level. •All these effects are observed in human fibroblasts and endothelial cells. -- Abstract: Receptor Activator of NFκB Ligand (RANKL) and its decoy receptor osteoprotegerin (OPG) have been shown to play a role not only in bone remodeling but also in inflammation, arterial calcification and atherosclerotic plaque rupture. In human smooth muscle cells, Cu{sup 2+}-oxidized LDL (CuLDL) 10–50 μg/ml increased reactive oxygen species (ROS) and RANKL level in a dose-dependent manner, whereas OPG level was not affected. The lipid extract of CuLDL reproduced the effects of the whole particle. Vivit, an inhibitor of the transcription factor NFAT, reduced the CuLDL-induced increase in RANKL, whereas PKA and NFκB inhibitors were ineffective. LDL oxidized by myeloperoxidase (MPO-LDL), or other pro-oxidant conditions such as ultraviolet A (UVA) irradiation, incubation with H{sub 2}O{sub 2} or with buthionine sulfoximine (BSO), an inhibitor of glutathione synthesis{sub ,} also induced an oxidative stress and enhanced RANKL level. The increase in RANKL in pro-oxidant conditions was also observed in fibroblasts and endothelial cells. Since RANKL is involved in myocardial inflammation, vascular calcification and plaque rupture, this study highlights a new mechanism whereby OxLDL might, by generation of an oxidative stress, exert a deleterious effect on different cell types of the arterial wall.

  5. Increasing Level of Leisure Physical Activity Could Reduce the Risk of Hip Fracture in Older Women

    PubMed Central

    Rong, Ke; Liu, Xiao-yu; Wu, Xu-hua; Li, Xiao-liu; Xia, Qing-quan; Chen, Jiong; Yin, Xiao-fan

    2016-01-01

    Abstract We carried out the study to investigate and quantitatively assess the potential association between current level of physical activity and the risk of osteoporosis hip fracture in older women. Relevant publications before October 2015 were identified using the PubMed and Ovid searching tools. A dose–response meta-analysis was carried out to combine and analysis results. Fourteen prospective studies were included in the meta-analysis. A general analysis of 9 studies showed a significant inverse relationship between increasing level of physical activity and risk of hip fracture in older women [relative risk (RR) = 0.93, 95% confidence interval (95% CI): 0.91–0.96]. The result of a sensitivity analysis was consistent with the general analysis (RR = 0.94, 95% CI: 0.93–0.96). The association between increasing level of physical activity and risk of wrist fracture was not statistically significant in a general analysis of three studies (RR = 1.004, 95% CI: 0.98–1.03). A potential direct association between increasing level of physical activity and risk of wrist fracture was observed after removing 1 study with the greatest weight (RR = 1.01, 95% CI: 1.00–1.03). No significant publication bias was observed in our analysis. Our results show that increasing level of physical activity within an appropriate range may reduce the risk of hip fracture but not the risk of wrist fracture in older women. PMID:26986111

  6. Chronic lithium treatment increased intracellular S100ß levels in rat primary neuronal culture.

    PubMed

    Emamghoreishi, Masoumeh; Keshavarz, Mojtaba; Nekooeian, Ali Akbar

    2015-01-01

    S100ß a neurotrophic factor mainly released by astrocytes, has been implicated in the pathogenesis of bipolar disorder. Thus, lithium may exert its neuroprotective effects to some extent through S100ß. Furthermore, the possible effects of lithium on astrocytes as well as on interactions between neurons and astrocytes as a part of its mechanisms of actions are unknown. This study was undertaken to determine the effect of lithium on S100β in neurons, astrocytes and a mixture of neurons and astrocytes. Rat primary astrocyte, neuronal and mixed neuro-astroglia cultures were prepared from cortices of 18-day's embryos. Cell cultures were exposed to lithium (1mM) or vehicle for 1day (acute) or 7 days (chronic). RT-PCR and ELISA determined S100β mRNA and intra- and extracellular protein levels. Chronic lithium treatment significantly increased intracellular S100β in neuronal and neuro-astroglia cultures in comparison to control cultures (P<0.05). Acute and chronic lithium treatments exerted no significant effects on intracellular S100β protein levels in astrocytes, and extracellular S100β protein levels in three studied cultures as compared to control cultures. Acute and chronic lithium treatments did not significantly alter S100β mRNA levels in three studied cultures, compared to control cultures. Chronic lithium treatment increased intracellular S100ß protein levels in a cell-type specific manner which may favor its neuroprotective action. The findings of this study suggest that lithium may exert its neuroprotective action, at least partly, by increasing neuronal S100ß level, with no effect on astrocytes or interaction between neurons and astrocytes.

  7. Staphylococcal enterotoxin A-induced fever is associated with increased circulating levels of cytokines in rabbits.

    PubMed Central

    Huang, W T; Lin, M T; Won, S J

    1997-01-01

    Rabbits were injected intravenously with 10 to 100 ng of staphylococcal enterotoxin A (SEA) per kg, and colonic temperatures were monitored. The febrile responses were compared with circulating levels of interferon (IFN), tumor necrosis factor (TNF), interleukin-1 (IL-1), IL-2, and IL-6 just before the injection of SEA. Both colonic temperatures and circulating levels of IFN, TNF, and IL-2 started to rise at 1 to 2 h and reached their peak levels at 3 to 5 h after SEA injection. Both the fever and the increased circulating levels of IFN, TNF, and IL-2 produced by SEA were decreased by pretreatment with indomethacin (a cyclo-oxygenase inhibitor) (15 mg/kg, intraperitoneally), anisomycin (a protein synthesis inhibitor) (15 mg/kg, subcutaneously), or dexamethasone (an effective anti-inflammatory and immunosuppressive agent) (4 mg/kg, intravenously) in rabbits. Rabbits were injected intravenously with 30 ng of SEA per kg on four consecutive days, and colonic temperatures were monitored. Compared to rabbits that received the single injection of SEA, rabbits that received four consecutive injections of SEA showed a lesser increase in circulating levels of IFN, TNF, and IL-2 as well as colonic temperatures in response to an intravenous dose of SEA (30 ng/kg). The data suggest that the prevention of the febrile response elicited by SEA by indomethacin, anisomycin, or dexamethasone is due to prevention by these compounds of the increase in the circulating levels of IFN, TNF, and IL-2. The pyrogenic hyporesponsiveness to repeated injection of SEA is associated with decreased production of these circulating cytokines. PMID:9199433

  8. Increased extracellular levels of glutamate in the hippocampus of chronically epileptic rats.

    PubMed

    Soukupova, M; Binaschi, A; Falcicchia, C; Palma, E; Roncon, P; Zucchini, S; Simonato, M

    2015-08-20

    An increase in the release of excitatory amino acids has consistently been observed in the hippocampus during seizures, both in humans and animals. However, very little or nothing is known about the extracellular levels of glutamate and aspartate during epileptogenesis and in the interictal chronic period of established epilepsy. The aim of this study was to systematically evaluate the relationship between seizure activity and changes in hippocampal glutamate and aspartate extracellular levels under basal and high K(+)-evoked conditions, at various time-points in the natural history of experimental temporal lobe epilepsy, using in vivo microdialysis. Hippocampal extracellular glutamate and aspartate levels were evaluated: 24h after pilocarpine-induced status epilepticus (SE); during the latency period preceding spontaneous seizures; immediately after the first spontaneous seizure; in the chronic (epileptic) period. We found that (i) basal (spontaneous) glutamate outflow is increased in the interictal phases of the chronic period, whereas basal aspartate outflow remains stable for the entire course of the disease; (ii) high K(+) perfusion increased glutamate and aspartate outflow in both control and pilocarpine-treated animals, and the overflow of glutamate was clearly increased in the chronic group. Our data suggest that the glutamatergic signaling is preserved and even potentiated in the hippocampus of epileptic rats, and thus may favor the occurrence of spontaneous recurrent seizures. Together with an impairment of GABA signaling (Soukupova et al., 2014), these data suggest that a shift toward excitation occurs in the excitation/inhibition balance in the chronic epileptic state. PMID:26073699

  9. Salicylic Acid Treatment Increases the Levels of Triterpene Glycosides in Black Cohosh (Actaea Racemosa) Rhizomes.

    PubMed

    De Capite, Annette; Lancaster, Tyler; Puthoff, David

    2016-01-01

    Black cohosh (Actaea racemosa) serves as the host plant for the Appalachian azure butterfly, Celastrina neglectamajor. Overharvesting of Black cohosh for the dietary supplement industry may result in its extirpation, and may also cause the elimination of the dependent butterfly. One way to increase or maintain the number of host plants in forested environments would be to reduce the number harvested, for example by increasing the levels of the desired metabolites in Black cohosh rhizomes. The secondary metabolites actein and deoxyactein are triterpene glycosides and are among the compounds associated with the putative activity of Black cohosh extracts. Acetein and deoxyacetein are used to standardize Black cohosh supplements. To gain an understanding of mechanisms that may control actein and deoxyactein accumulation, Black cohosh rhizomes were treated with exogenous salicylic acid, jasmonic acid, or ethylene, or were mechanically wounded. Salicylic acid treatment significantly increased the levels of actein and deoxyactein in the rhizome of Black cohosh, suggesting that the synthesis of triterpene glycosides is controlled in part by salicylic acid. Using salicylic acid or related chemicals to increase the levels of actein and deoxyactein in rhizomes may help supply the supplement industry and, simultaneously, help conserve Black cohosh and species dependent upon it. PMID:26634573

  10. Salicylic Acid Treatment Increases the Levels of Triterpene Glycosides in Black Cohosh (Actaea Racemosa) Rhizomes.

    PubMed

    De Capite, Annette; Lancaster, Tyler; Puthoff, David

    2016-01-01

    Black cohosh (Actaea racemosa) serves as the host plant for the Appalachian azure butterfly, Celastrina neglectamajor. Overharvesting of Black cohosh for the dietary supplement industry may result in its extirpation, and may also cause the elimination of the dependent butterfly. One way to increase or maintain the number of host plants in forested environments would be to reduce the number harvested, for example by increasing the levels of the desired metabolites in Black cohosh rhizomes. The secondary metabolites actein and deoxyactein are triterpene glycosides and are among the compounds associated with the putative activity of Black cohosh extracts. Acetein and deoxyacetein are used to standardize Black cohosh supplements. To gain an understanding of mechanisms that may control actein and deoxyactein accumulation, Black cohosh rhizomes were treated with exogenous salicylic acid, jasmonic acid, or ethylene, or were mechanically wounded. Salicylic acid treatment significantly increased the levels of actein and deoxyactein in the rhizome of Black cohosh, suggesting that the synthesis of triterpene glycosides is controlled in part by salicylic acid. Using salicylic acid or related chemicals to increase the levels of actein and deoxyactein in rhizomes may help supply the supplement industry and, simultaneously, help conserve Black cohosh and species dependent upon it.

  11. Mitochondrial impairment increases FL-PINK1 levels by calcium-dependent gene expression☆

    PubMed Central

    Gómez-Sánchez, Rubén; Gegg, Matthew E.; Bravo-San Pedro, José M.; Niso-Santano, Mireia; Alvarez-Erviti, Lydia; Pizarro-Estrella, Elisa; Gutiérrez-Martín, Yolanda; Alvarez-Barrientos, Alberto; Fuentes, José M.; González-Polo, Rosa Ana; Schapira, Anthony H.V.

    2014-01-01

    Mutations of the PTEN-induced kinase 1 (PINK1) gene are a cause of autosomal recessive Parkinson's disease (PD). This gene encodes a mitochondrial serine/threonine kinase, which is partly localized to mitochondria, and has been shown to play a role in protecting neuronal cells from oxidative stress and cell death, perhaps related to its role in mitochondrial dynamics and mitophagy. In this study, we report that increased mitochondrial PINK1 levels observed in human neuroblastoma SH-SY5Y cells after carbonyl cyanide m-chlorophelyhydrazone (CCCP) treatment were due to de novo protein synthesis, and not just increased stabilization of full length PINK1 (FL-PINK1). PINK1 mRNA levels were significantly increased by 4-fold after 24 h. FL-PINK1 protein levels at this time point were significantly higher than vehicle-treated, or cells treated with CCCP for 3 h, despite mitochondrial content being decreased by 29%. We have also shown that CCCP dissipated the mitochondrial membrane potential (Δψm) and induced entry of extracellular calcium through L/N-type calcium channels. The calcium chelating agent BAPTA-AM impaired the CCCP-induced PINK1 mRNA and protein expression. Furthermore, CCCP treatment activated the transcription factor c-Fos in a calcium-dependent manner. These data indicate that PINK1 expression is significantly increased upon CCCP-induced mitophagy in a calcium-dependent manner. This increase in expression continues after peak Parkin mitochondrial translocation, suggesting a role for PINK1 in mitophagy that is downstream of ubiquitination of mitochondrial substrates. This sensitivity to intracellular calcium levels supports the hypothesis that PINK1 may also play a role in cellular calcium homeostasis and neuroprotection. PMID:24184327

  12. Histone deacetylases 6 increases the cyclic adenosine monophosphate level and promotes renal cyst growth.

    PubMed

    Wu, Ming; Mei, Changlin

    2016-07-01

    Autosomal dominant polycystic kidney disease (ADPKD) is characterized by abnormal enhanced cell proliferation and fluid secretion, which are triggered by increased levels of cyclic adenosine monophosphate (cAMP). Cebotaru et al. showed that a HDAC6 inhibitor reduced the cAMP level and inhibited cyst formation in Pkd1 knockout mice, which may become a new potential therapeutic agent for ADPKD. This study also raised several intriguing questions that might advance our understanding of the molecular pathogenesis of ADPKD. PMID:27312442

  13. Evidence that elevated CO2 levels can indirectly increase rhizosphere denitrifier activity

    NASA Technical Reports Server (NTRS)

    Smart, D. R.; Ritchie, K.; Stark, J. M.; Bugbee, B.

    1997-01-01

    We examined the influence of elevated CO2 concentration on denitrifier enzyme activity in wheat rhizoplanes by using controlled environments and solution culture techniques. Potential denitrification activity was from 3 to 24 times higher on roots that were grown under an elevated CO2 concentration of 1,000 micromoles of CO2 mol-1 than on roots grown under ambient levels of CO2. Nitrogen loss, as determined by a nitrogen mass balance, increased with elevated CO2 levels in the shoot environment and with a high NO3- concentration in the rooting zone. These results indicated that aerial CO2 concentration can play a role in rhizosphere denitrifier activity.

  14. Increased serum osteopontin levels in autistic children: relation to the disease severity.

    PubMed

    Al-ayadhi, Laila Y; Mostafa, Gehan A

    2011-10-01

    Autoimmunity to brain may play an etiopathogenic role in autism. Osteopontin is a pro-inflammatory cytokine that has been shown to play an important role in various autoimmune neuroinflammatory diseases. Osteopontin induces IL-17 production by T-helper 17 lymphocytes, the key players in the pathogenesis of autoimmune disorders. Anti-osteopontin treatment reduces the clinical severity of some autoimmune neuroinflammatory diseases by reducing IL-17 production. We are the first to measure serum osteopontin levels, by ELISA, in 42 autistic children in comparison to 42 healthy-matched children. The relationship between serum osteopontin levels and the severity of autism, which was assessed by using the Childhood Autism Rating Scale (CARS), was also studied. Autistic children had significantly higher serum osteopontin levels than healthy controls (P<0.001). Increased serum osteopontin levels were found in 80.95% (34/42) of autistic children. Children with severe autism had significantly higher serum osteopontin levels than patients with mild to moderate autism (P=0.02). Moreover, serum osteopontin levels of autistic patients had significant positive correlations with CARS (P=0.007). In conclusions, serum osteopontin levels were increased in many autistic children and they were significantly correlated to the severity of autism. Further wide-scale studies are warranted to shed light on the etiopathogenic role of osteopontin in autism and to investigate its relation to IL-17 and brain-specific auto-antibodies, which are indicators of autoimmunity, in these patients. The therapeutic role of anti-osteopontin antibodies in amelioration of autistic manifestations should also be studied.

  15. Benefits and costs of increased levels of corticosterone in seabird chicks

    USGS Publications Warehouse

    Kitaysky, A.S.; Kitaiskaia, E.V.; Piatt, J.F.; Wingfield, J.C.

    2003-01-01

    Seabird chicks respond to food shortages by increasing corticosterone (cort) secretion, which is probably associated with fitness benefits and costs. To examine this, we experimentally increased levels of circulating cort in captive black-legged kittiwake chicks fed ad libitum. We found that cort-implanted chicks begged more frequently and were more aggressive compared to controls. These behavioral modifications must be beneficial to chicks as they facilitate acquisition of food from the parents and might trigger brood reduction and reduced competition for food. Cort-implanted chicks also increased food intake; however, their growth rates were similar to controls. To examine the costs of chronically increased circulating levels of cort, we removed cort implants and, after a 10-day recovery period, tested cognitive abilities of young kittiwakes. We found that the ability of kittiwakes to associate a visual cue with the presence of food in a choice situation was compromised by the experimental elevation of cort during development. To examine the long-term costs of increased levels of cort, 8 months later we tested the performance of the same individuals in a spatial task requiring them to make a detour around a barrier in order to escape from an enclosure. Individuals treated with cort during development took significantly more time to solve this task compared to controls. The results of this study suggest that the adrenocortical response of a developing bird to environmental stressors is associated with both benefits (increased food intake, foraging behavior, and aggression) and costs (low growth efficiency and compromised cognitive abilities later in life). This provides an evolutionary framework for relating juvenile physiological traits to fitness of birds in subsequent life-history stages. ?? 2003 Elsevier Science (USA). All rights reserved.

  16. Benefits and costs of increased levels of corticosterone in seabird chicks.

    PubMed

    Kitaysky, A S; Kitaiskaia, E V; Piatt, J F; Wingfield, J C

    2003-01-01

    Seabird chicks respond to food shortages by increasing corticosterone (cort) secretion, which is probably associated with fitness benefits and costs. To examine this, we experimentally increased levels of circulating cort in captive black-legged kittiwake chicks fed ad libitum. We found that cort-implanted chicks begged more frequently and were more aggressive compared to controls. These behavioral modifications must be beneficial to chicks as they facilitate acquisition of food from the parents and might trigger brood reduction and reduced competition for food. Cort-implanted chicks also increased food intake; however, their growth rates were similar to controls. To examine the costs of chronically increased circulating levels of cort, we removed cort implants and, after a 10-day recovery period, tested cognitive abilities of young kittiwakes. We found that the ability of kittiwakes to associate a visual cue with the presence of food in a choice situation was compromised by the experimental elevation of cort during development. To examine the long-term costs of increased levels of cort, 8 months later we tested the performance of the same individuals in a spatial task requiring them to make a detour around a barrier in order to escape from an enclosure. Individuals treated with cort during development took significantly more time to solve this task compared to controls. The results of this study suggest that the adrenocortical response of a developing bird to environmental stressors is associated with both benefits (increased food intake, foraging behavior, and aggression) and costs (low growth efficiency and compromised cognitive abilities later in life). This provides an evolutionary framework for relating juvenile physiological traits to fitness of birds in subsequent life-history stages.

  17. Maternal dietary omega-3 fatty acid intake increases resolvin and protectin levels in the rat placenta

    PubMed Central

    Jones, Megan L.; Mark, Peter J.; Keelan, Jeffrey A.; Barden, Anne; Mas, Emilie; Mori, Trevor A.; Waddell, Brendan J.

    2013-01-01

    Placental inflammation is associated with several pregnancy disorders. Inflammation is limited by anti-inflammatory and proresolving mechanisms, the latter partly mediated by resolvins and protectins derived from omega-3 polyunsaturated fatty acids (n-3PUFA). We examined effects of dietary n-3PUFAs on levels of resolvins, protectins, and lipoxygenase (ALOX) enzymes in the rat placenta. Rats consumed standard (Std) or high n-3PUFA (Hn3) diets from day 1 of pregnancy; tissues were collected on day 17 or 22 (term = day 23). Maternal Hn3 diet increased resolvin and protectin precursors, 18R/S-HEPE (P < 0.001), and 17R/S-HDHA (P < 0.01) at both days. Resolvins (17R-RvD1 and RvD1) increased at day 22 (P < 0.001) after Hn3 consumption, coincident with higher Alox15b and Alox5 mRNA expression, while RvD2 increased at both days (P < 0.05). Protectins, PD1, and 10S,17S-DiHDHA increased over late gestation (P < 0.001), coincident with higher Alox15 mRNA expression (P < 0.001) and further increased with Hn3 diet (P < 0.05). Maternal systemic and placental proinflammatory mediators were not suppressed by Hn3 diet; systemic IL1β, placental Il1β, and Il6 mRNA expression increased marginally with Hn3 at day 22 (P < 0.001), while Ptgs1 (Cox1) expression increased both days (P < 0.05). Our data indicate that maternal n-3PUFA supplementation enhances expression of enzymes in the n-3PUFA metabolic pathway and increases placental levels of resolvins and protectins. PMID:23723388

  18. The ATF6-Met[67]Val substitution is associated with increased plasma cholesterol levels

    PubMed Central

    Meex, Steven J.R.; Weissglas-Volkov, Daphna; van der Kallen, Carla J.H.; Thuerauf, Donna J.; van Greevenbroek, Marleen M.J.; Schalkwijk, Casper G.; Stehouwer, Coen D.A.; Feskens, Edith J.M.; Heldens, Lonneke; Ayoubi, Torik A.; Hofker, Marten H.; Wouters, Bradly G.; Vlietinck, Robert; Sinsheimer, Janet S.; Taskinen, Marja-Riitta; Kuusisto, Johanna; Laakso, Markku; de Bruin, Tjerk W.A.; Pajukanta, Päivi; Glembotski, Christopher C.

    2009-01-01

    Objective Activating Transcription Factor 6 (ATF6) is a sensor of the endoplasmic reticulum stress response and regulates expression of several key lipogenic genes. We utilized a two-stage design to investigate whether ATF6 polymorphisms are associated with lipids in subjects at increased risk for cardiovascular disease (CVD). Methods and Results In stage 1, 13 tag-SNPs were tested for association in Dutch samples ascertained for Familial Combined Hyperlipidemia (FCHL) or increased risk for CVD (CVR). In stage 2, we further investigated the SNP with the strongest association from stage 1, a Methionine/Valine substitution at amino-acid 67, in Finnish FCHL families and in subjects with CVR from METSIM, a Finnish population-based cohort. The combined analysis of both stages reached region-wide significance (P=9×10−4), but this association was not seen in the entire METSIM cohort. Our functional analysis demonstrated that Valine at position 67 augments ATF6 protein and its targets Grp78 and Grp94 as well as increases luciferase expression through Grp78 promoter. Conclusions A common nonsynonymous variant in ATF6 increases ATF6 protein levels and is associated with cholesterol levels in subjects at increased risk for CVD, but this association was not seen in a population-based cohort. Further replication is needed to confirm this variant's role in lipids. PMID:19667116

  19. Blood parameters in growing pigs fed increasing levels of bacterial protein meal

    PubMed Central

    Hellwing, Anne Louise F; Tauson, Anne-Helene; Skrede, Anders

    2007-01-01

    The experiment investigated the effects of increasing dietary levels of bacterial protein meal (BPM) on various blood parameters reflecting protein and fat metabolism, liver function, and purine base metabolism in growing pigs. Sixteen barrows were allocated to four different experimental diets. The control diet was based on soybean meal. In the other three diets soybean meal was replaced with increasing levels of BPM, approximately 17%, 35%, and 50% of the nitrogen being derived from BPM. Blood samples from the jugular vein were taken when the body weights of the pigs were approximately 10 kg, 21 kg, 45 kg, and 77 kg. The blood parameters reflecting fat metabolism and liver function were not affected by diet. Both the plasma albumin and uric acid concentrations tended to decrease (P = 0.07 and 0.01, respectively) with increasing dietary BPM content, whereas the plasma glucose concentration tended to increase (P = 0.07) with increasing dietary BPM content. It was concluded that up to 50% of the nitrogen could be derived from BPM without affecting metabolic function, as reflected in the measured blood parameters. PMID:17996082

  20. Cross-linking and the molecular packing of corneal collagen

    NASA Technical Reports Server (NTRS)

    Yamauchi, M.; Chandler, G. S.; Tanzawa, H.; Katz, E. P.

    1996-01-01

    We have quantitatively characterized, for the first time, the cross-linking in bovine cornea collagen as a function of age. The major iminium reducible cross-links were dehydro-hydroxylysinonorleucine (deH-HLNL) and dehydro-histidinohydroxymerodesmosine (deH-HHMD). The former rapidly diminished after birth; however, the latter persisted in mature animals at a level of 0.3 - 0.4 moles/mole of collagen. A nonreducible cross-link, histidinohydroxylysinonorleucine (HHL), previously found only in skin, was also found to be a major mature cross-link in cornea. The presence of HHL indicates that cornea fibrils have a molecular packing similar to skin collagen. However, like deH-HHMD, the HHL content in corneal fibrils only reaches a maximum value with time about half that of skin. These data suggest that the corneal fibrils are comprised of discrete filaments that are internally stabilized by HHL and deH-HHMD cross-links. This pattern of intermolecular cross-linking would facilitate the special collagen swelling property required for corneal transparency.

  1. A gene stacking approach leads to engineered plants with highly increased galactan levels in Arabidopsis

    DOE PAGESBeta

    Gondolf, Vibe M.; Stoppel, Rhea; Ebert, Berit; Rautengarten, Carsten; Liwanag, April J.M.; Loqué, Dominique; Scheller, Henrik V.

    2014-12-10

    Background: Engineering of plants with a composition of lignocellulosic biomass that is more suitable for downstream processing is of high interest for next-generation biofuel production. Lignocellulosic biomass contains a high proportion of pentose residues, which are more difficult to convert into fuels than hexoses. Therefore, increasing the hexose/pentose ratio in biomass is one approach for biomass improvement. A genetic engineering approach was used to investigate whether the amount of pectic galactan can be specifically increased in cell walls of Arabidopsis fiber cells, which in turn could provide a potential source of readily fermentable galactose. Results: First it was tested ifmore » overexpression of various plant UDP-glucose 4-epimerases (UGEs) could increase the availability of UDP-galactose and thereby increase the biosynthesis of galactan. Constitutive and tissue-specific expression of a poplar UGE and three Arabidopsis UGEs in Arabidopsis plants could not significantly increase the amount of cell wall bound galactose. We then investigated co-overexpression of AtUGE2 together with the β-1,4-galactan synthase GalS1. Co-overexpression of AtUGE2 and GalS1 led to over 80% increase in cell wall galactose levels in Arabidopsis stems, providing evidence that these proteins work synergistically. Furthermore, AtUGE2 and GalS1 overexpression in combination with overexpression of the NST1 master regulator for secondary cell wall biosynthesis resulted in increased thickness of fiber cell walls in addition to the high cell wall galactose levels. Immunofluorescence microscopy confirmed that the increased galactose was present as β-1,4-galactan in secondary cell walls. Conclusions: This approach clearly indicates that simultaneous overexpression of AtUGE2 and GalS1 increases the cell wall galactose to much higher levels than can be achieved by overexpressing either one of these proteins alone. Moreover, the increased galactan content in fiber cells while

  2. A gene stacking approach leads to engineered plants with highly increased galactan levels in Arabidopsis

    SciTech Connect

    Gondolf, Vibe M.; Stoppel, Rhea; Ebert, Berit; Rautengarten, Carsten; Liwanag, April J.M.; Loqué, Dominique; Scheller, Henrik V.

    2014-12-10

    Background: Engineering of plants with a composition of lignocellulosic biomass that is more suitable for downstream processing is of high interest for next-generation biofuel production. Lignocellulosic biomass contains a high proportion of pentose residues, which are more difficult to convert into fuels than hexoses. Therefore, increasing the hexose/pentose ratio in biomass is one approach for biomass improvement. A genetic engineering approach was used to investigate whether the amount of pectic galactan can be specifically increased in cell walls of Arabidopsis fiber cells, which in turn could provide a potential source of readily fermentable galactose. Results: First it was tested if overexpression of various plant UDP-glucose 4-epimerases (UGEs) could increase the availability of UDP-galactose and thereby increase the biosynthesis of galactan. Constitutive and tissue-specific expression of a poplar UGE and three Arabidopsis UGEs in Arabidopsis plants could not significantly increase the amount of cell wall bound galactose. We then investigated co-overexpression of AtUGE2 together with the β-1,4-galactan synthase GalS1. Co-overexpression of AtUGE2 and GalS1 led to over 80% increase in cell wall galactose levels in Arabidopsis stems, providing evidence that these proteins work synergistically. Furthermore, AtUGE2 and GalS1 overexpression in combination with overexpression of the NST1 master regulator for secondary cell wall biosynthesis resulted in increased thickness of fiber cell walls in addition to the high cell wall galactose levels. Immunofluorescence microscopy confirmed that the increased galactose was present as β-1,4-galactan in secondary cell walls. Conclusions: This approach clearly indicates that simultaneous overexpression of AtUGE2 and GalS1 increases the cell wall galactose to much higher levels than can be achieved by overexpressing either one of these proteins alone. Moreover, the increased galactan content in

  3. Can Population Levels of Physical Activity be Increased? Global Evidence and Experience

    PubMed Central

    Pratt, Michael; Perez, Lilian G.; Goenka, Shifalika; Brownson, Ross C.; Bauman, Adrian; Sarmiento, Olga Lucia; Hallal, Pedro C.

    2016-01-01

    Physical inactivity is one of the most important contributors to the global burden of disease and has become a global public health priority. We review the evidence on physical activity (PA) interventions, actions, and strategies that have the greatest potential to increase PA at the population level. Using the socio-ecological framework to conceptualize PA interventions, we show that PA can be targeted at multiple levels of influence and by multiple sectors outside the health system. Examples of promoting PA on a national scale are presented from Finland, Canada, Brazil, and Colombia. A strong policy framework, consistent investment in public health programs, multi-sectoral support and actions, and good surveillance characterize each of these success stories. Increasing PA globally will depend on successfully applying and adapting these lessons around the world taking into account country, culture, and context. PMID:25304047

  4. Mannosylerythritol lipid increases levels of galactoceramide in and neurite outgrowth from PC12 pheochromocytoma cells.

    PubMed

    Shibahara, M; Zhao, X; Wakamatsu, Y; Nomura, N; Nakahara, T; Jin, C; Nagaso, H; Murata, T; Yokoyama, K K

    2000-07-01

    We report here that a microbial extracellular glycolipid,mannosylerythritol lipid (MEL), induces the outgrowth ofneurites from and enhances the activity of acetylcholinesterase(AChE) in PC12 pheochromocytoma cells. Furthermore, treatment ofPC12 cells with MEL increased levels of galactosylceramide(Galbeta1-1'Cer; GalCer). Exposure of PC12 cells to exogenous GalCer caused the dose-dependent outgrowth ofneurites. By contrast, treatment of PC12 cells with nerve growthfactor (NGF) did not increase the level of GalCer in the cells. The neurite-related morphological changes induced by GalCerdifferend from those induced by NGF, indicating differencesbetween the signal transduction pathways triggered by NGF and by GalCer. PMID:19002832

  5. An increase in the rate of global mean sea level rise since 2010

    NASA Astrophysics Data System (ADS)

    Yi, Shuang; Sun, Wenke; Heki, Kosuke; Qian, An

    2015-05-01

    The global mean sea level (GMSL) was reported to have dropped 5 mm due to the 2010/2011 La Niña and have recovered in 1 year. With longer observations, it is shown that the GMSL went further up to a total amount of 11.6 mm by the end of 2012, excluding the 3.0 mm/yr background trend. A reconciled sea level budget, based on observations by Argo project, altimeter, and gravity satellites, reveals that the true GMSL rise has been masked by El Niño-Southern Oscillation-related fluctuations and its rate has increased since 2010. After extracting the influence of land water storage, it is shown that the GMSL has been rising at a rate of 4.4 ± 0.5 mm/yr for more than 3 years, due to an increase in the rate of both land ice loss and steric change.

  6. Decreased Integrity, Content, and Increased Transcript Level of Mitochondrial DNA Are Associated with Keratoconus

    PubMed Central

    Hao, Xiao-Dan; Chen, Zhao-Li; Qu, Ming-Li; Zhao, Xiao-Wen; Li, Su-Xia; Chen, Peng

    2016-01-01

    Oxidative stress may play an important role in the pathogenesis of keratoconus (KC). Mitochondrial DNA (mtDNA) is involved in mitochondrial function, and the mtDNA content, integrity, and transcript level may affect the generation of reactive oxygen species (ROS) and be involved in the pathogenesis of KC. We designed a case-control study to research the relationship between KC and mtDNA integrity, content and transcription. One-hundred ninety-eight KC corneas and 106 normal corneas from Chinese patients were studied. Quantitative real-time PCR was used to measure the relative mtDNA content, transcript levels of mtDNA and related genes. Long-extension PCR was used to detect mtDNA damage. ROS, mitochondrial membrane potential and ATP were measured by respective assay kit, and Mito-Tracker Green was used to label the mitochondria. The relative mtDNA content of KC corneas was significantly lower than that of normal corneas (P = 9.19×10−24), possibly due to decreased expression of the mitochondrial transcription factor A (TFAM) gene (P = 3.26×10−3). In contrast, the transcript levels of mtDNA genes were significantly increased in KC corneas compared with normal corneas (NADH dehydrogenase subunit 1 [ND1]: P = 1.79×10−3; cytochrome c oxidase subunit 1 [COX1]: P = 1.54×10−3; NADH dehydrogenase subunit 1, [ND6]: P = 4.62×10−3). The latter may be the result of increased expression levels of mtDNA transcription-related genes mitochondrial RNA polymerase (POLRMT) (P = 2.55×10−4) and transcription factor B2 mitochondrial (TFB2M) (P = 7.88×10−5). KC corneas also had increased mtDNA damage (P = 3.63×10−10), higher ROS levels, and lower mitochondrial membrane potential and ATP levels compared with normal corneas. Decreased integrity, content and increased transcript level of mtDNA are associated with KC. These changes may affect the generation of ROS and play a role in the pathogenesis of KC. PMID:27783701

  7. Sildenafil increases serum testosterone levels by a direct action on the testes.

    PubMed

    Spitzer, M; Bhasin, S; Travison, T G; Davda, M N; Stroh, H; Basaria, S

    2013-11-01

    Phosphodiesterase-5-inhibitors, such as sildenafil, increase intracavernosal cyclic guanosine monophosphate levels, which results in corporal smooth muscle relaxation and penile erection. Here, we determined the effects of sildenafil administration on the hypothalamic-pituitary-gonadal axis in men with erectile dysfunction and low testosterone levels. The Testosterone and Erectile Dysfunction trial (ClinicalTrials.gov # NCT00512707) initially administered an optimized dose of sildenafil to 140 men, aged 40-70 years with erectile dysfunction, low serum total testosterone (<11.4 nmol/L; 330 ng/dL) and/or free testosterone (<173 pmol/L; 50 pg/mL) over 3-7 weeks. Sex steroids and gonadotropins were measured at baseline and after sildenafil optimization in a longitudinal study without a separate control group. Serum testosterone, dihydrotestosterone (DHT) and oestrogens were measured using liquid chromatography-tandem mass spectrometry. Administration of an optimized dose of sildenafil was associated with mean increases of 3.6 nmol/L (103 ng/dL; p < 0.001) and 110 pmol/L (31.7 pg/mL; p < 0.001) in total and free testosterone levels respectively. This was accompanied by parallel increases in serum DHT (0.17 nmol/L; 4.9 ng/dL; p < 0.001) and oestradiol (14 pmol/L; 3.7 pg/mL; p < 0.001) and significant suppression of luteinizing hormone (change -1.3 units/L; p = 0.003) levels, suggesting a direct effect at the testicular level. Androstenedione and oestrone increased by 1.3 nmol/L (38 ng/dL; p = 0.011) and 10.7 pmol/L (2.9 pg/mL; p = 0.012), respectively, supporting a possible effect of sildenafil on adrenal steroidogenesis. In conclusion, sildenafil administration was associated with increased testosterone levels likely ascribable to a direct effect on the testis.

  8. Crosslinkable fumed silica-based nanocomposite electrolytes: role of methacrylate monomer in formation of crosslinked silica network

    NASA Astrophysics Data System (ADS)

    Yerian, Jeffrey A.; Khan, Saad A.; Fedkiw, Peter S.

    The electrochemical and rheological properties of composite polymer electrolytes (CPEs) based on fumed silica with tethered crosslinkable groups are reported. These silica nanoparticles are dispersed in electrolytes consisting of poly(ethylene glycol) dimethyl ether (PEGdm)+lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) to which various methacrylate monomers, such as methyl (MMA), ethyl (EMA), butyl (BMA), n-hexyl (HMA), and n-dodecyl (DMA) methacrylate, are added. The methacrylate monomer facilitates creation of chemical crosslinks between fumed silica particles and formation of a crosslinked network. In this study, the effects of concentration and alkyl chain length of the monomers on conductivity, dynamic rheology, open-circuit interfacial stability, and cell voltage in lithium-lithium cell cycling are examined. Increasing the length of the monomer alkyl chain enhances both conductivity and elastic modulus of the crosslinked CPE. In contrast, increasing monomer concentration results in higher elastic modulus, but reduced conductivity. Lithium-lithium cell cycling and open-circuit interfacial stability results did not correlate with alkyl chain length. That is, for the lithium-lithium cycling studies, all crosslinked samples exhibit higher half-cycle voltage compared to non-crosslinked samples; however, the open-circuit interfacial stability of CPEs containing BMA and HMA exhibit improved stability compared to the other monomers and the CPE without monomer.

  9. Increased Plasma Levels of Pentraxin 3 Are Associated with Poor Prognosis of Colorectal Carcinoma Patients.

    PubMed

    Zhang, Jie; Wang, Tai-Yong; Niu, Xue-Cai

    2016-01-01

    Colorectal carcinoma (CRC) is one of the most common cancers globally. It is essential to identify a prognostic predictor for CRC. Pentraxin 3 (PTX3) is a glycoprotein that is secreted by a variety of human cells. It plays an important role in inflammation and immune regulation. Increasing evidence reveals that elevated PTX3 expression is related to poor prognosis in various cancers. The aim of the study was to determine the usefulness of plasma PTX3 level as a prognostic predictor in CRC. Total 184 CRC patients and 216 controls were included. Plasma levels of PTX3 were determined using Enzyme-linked immunosorbent assays. On admission, plasma PTX3 levels in CRC patients were higher than those in controls (11.8 ± 2.5 ng/ml vs. 3.1 ± 0.9 ng/ml, P < 0.001). After resection, plasma PTX3 levels in patients were decreased (6.0 ± 1.4 ng/ml, P = 0.007), and were elevated at the time of relapse (10.8 ± 2.8 ng/ml, P < 0.001). During the 60-month follow-up period, 108 patients suffered from relapse. Plasma PTX3 levels of ≥ 12 ng/ml on admission were associated with relapse (OR: 3.11, 95% CI: 1.74 ~ 6.29), and tumor-free survival rate in those patients with plasma PTX3 levels of ≥ 12 ng/ml was lower than that in other patients (P = 0.001). Furthermore, plasma PTX3 levels on admission showed positive linear correlations with plasma complement 3, 4 and 5b9 levels (P < 0.001, P < 0.001, P < 0.001). Therefore, we propose that PTX3 is an independent prognostic indicator in CRC. PMID:27568661

  10. Tenascin-C Deficiency in Apo E−/− Mouse Increases Eotaxin Levels: Implications for Atherosclerosis

    PubMed Central

    Wang, Lai; Shah, Prediman K.; Wang, Wei; Song, Lei; Yang, Mingjie; Sharifi, Behrooz G.

    2013-01-01

    Aim To investigate the potential role of inflammatory cytokines in apo E−/− mouse in response to deletion of Tenascin-C (TNC) gene. Methods and results We used antibody array and ELISA to compare the profile of circulating inflammatory cytokines in apo E−/− mice and apo E−/− TNC−/− double knockout mice. In addition, tissue culture studies were performed to investigate the activity of cells from each mouse genotype in vitro. Cytokine array analysis and subsequent ELISA showed that circulating eotaxin levels were selectively and markedly increased in response to TNC gene deletion in apo E−/− mice. In addition, considerable variation was noted in the circulating level of eotaxin among the control apo E−/− mouse group. Inbreeding of apo E−/− mice with high or low levels of plasma eotaxin showed that the level of eotaxin per se determines the extent of atherosclerosis in this mouse genotype. While endothelial cells from apo E−/− mice had low level of eotaxin expression, cells derived from apo E−/−TNC−/− mice expressed a high level of eotaxin. Transient transfection of eotaxin promoter-reporter constructs revealed that eotaxin expression is regulated at the transcriptional level by TNC. Histochemical analysis of aortic sections revealed the massive accumulation of mast cells in the adventitia of double KO mice lesions whereas no such accumulation was detected in the control group. Plasma from the apo E−/−TNC−/− mice markedly stimulated mast cell migration whereas plasma from the apo E−/− mice had no such effect. Conclusion These observations support the emerging hypothesis that TNC expression controls eotaxin level in apo E−/− mice and that this chemokine plays a key role in the development of atherosclerosis. PMID:23433402

  11. Increased Plasma Levels of Pentraxin 3 Are Associated with Poor Prognosis of Colorectal Carcinoma Patients.

    PubMed

    Zhang, Jie; Wang, Tai-Yong; Niu, Xue-Cai

    2016-01-01

    Colorectal carcinoma (CRC) is one of the most common cancers globally. It is essential to identify a prognostic predictor for CRC. Pentraxin 3 (PTX3) is a glycoprotein that is secreted by a variety of human cells. It plays an important role in inflammation and immune regulation. Increasing evidence reveals that elevated PTX3 expression is related to poor prognosis in various cancers. The aim of the study was to determine the usefulness of plasma PTX3 level as a prognostic predictor in CRC. Total 184 CRC patients and 216 controls were included. Plasma levels of PTX3 were determined using Enzyme-linked immunosorbent assays. On admission, plasma PTX3 levels in CRC patients were higher than those in controls (11.8 ± 2.5 ng/ml vs. 3.1 ± 0.9 ng/ml, P < 0.001). After resection, plasma PTX3 levels in patients were decreased (6.0 ± 1.4 ng/ml, P = 0.007), and were elevated at the time of relapse (10.8 ± 2.8 ng/ml, P < 0.001). During the 60-month follow-up period, 108 patients suffered from relapse. Plasma PTX3 levels of ≥ 12 ng/ml on admission were associated with relapse (OR: 3.11, 95% CI: 1.74 ~ 6.29), and tumor-free survival rate in those patients with plasma PTX3 levels of ≥ 12 ng/ml was lower than that in other patients (P = 0.001). Furthermore, plasma PTX3 levels on admission showed positive linear correlations with plasma complement 3, 4 and 5b9 levels (P < 0.001, P < 0.001, P < 0.001). Therefore, we propose that PTX3 is an independent prognostic indicator in CRC.

  12. Effect of modified starch and nanoclay particles on biodegradability and mechanical properties of cross-linked poly lactic acid.

    PubMed

    Shayan, M; Azizi, H; Ghasemi, I; Karrabi, M

    2015-06-25

    Mechanical properties and biodegradation of cross-linked poly(lactic acid) (PLA)/maleated thermoplastic starch (MTPS)/montmorillonite (MMT) nanocomposite were studied. Crosslinking was carried out by adding di-cumyl peroxide (DCP) in the presence of triallyl isocyanurate (TAIC) as coagent. At first, MTPS was prepared by grafting maleic anhydride (MA) to thermoplastic starch in internal mixer. Experimental design was performed by using Box-Behnken method at three variables: MTPS, nanoclay and TAIC at three levels. Results showed that increasing TAIC amount substantially increased the gel fraction, enhanced tensile strength, and caused a decrease in elongation at break. Biodegradation was prevented by increasing TAIC amount in nanocomposite. Increasing MTPS amount caused a slight increase in gel fraction and decreased the tensile strength of nanocomposite. Also, MTPS could increase the elongation at break of nanocomposite and improve the biodegradation. Nanoclay had no effect on the gel fraction, but it improved tensile strength. PMID:25839817

  13. Temporal aspects of increases in eye-neck activation levels during visually deficient near work.

    PubMed

    Richter, Hans O; Camilla, Lodin; Forsman, Mikael

    2012-01-01

    In an experimental study two levels of oculomotor load were induced via optical trial lenses. Trapezius muscle activity was measured with bipolar surface electromyography and normalized to a submaximal contraction. Sixty-six subjects with a median age of 36 (range 19-47, std 8) viewed a black and white Gabor grating (5 c/deg) for two 7-min periods monocularly through a 0 D lens or binocularly through -3.5 D lenses. The effect of time was separately regressed to EMG in two different subgroups of responders: a High-Oculomotor-Load (HOL) and a Low-Oculomotor-Load (LOL) group. A linear regression model was fitted on group level with exposure time on the x-axis and normalized trapezius muscle EMG (%RVE) on the y-axis. The slope coefficient was significantly positive in the -D blur condition for only the HOL subgroup of responders: 0.926 + Time(min 1-7) × 0.088 (p = 0.002, r(2)=0.865). There was no obvious sign of this activity to level off or to stabilize. These results suggest that professional information technology users that are exposed to a high level of oculomotor load, during extended times, are at an increased risk of exhibiting an increased trap.m. activity. PMID:22317234

  14. Masting promotes individual- and population-level reproduction by increasing pollination efficiency.

    PubMed

    Moreira, Xoaquín; Abdala-Roberts, Luis; Linhart, Yan B; Mooney, Kailen A

    2014-04-01

    Masting is a reproductive strategy defined as the intermittent and synchronized production of large seed crops by a plant population. The pollination efficiency hypothesis proposes that masting increases pollination success in plants. Despite its general appeal, no previous studies have used long-term data together with population- and individual-level analyses to assess pollination efficiency between mast and non-mast events. Here we rigorously tested the pollination efficiency hypothesis in ponderosa pine (Pinus ponderosa), a long-lived monoecious, wind-pollinated species, using a data set on 217 trees monitored annually for 20 years. Relative investment in male and female function by individual trees did not vary between mast and non-mast years. At both the population and individual level, the rate of production of mature female cones relative to male strobili production was higher in mast than non-mast years, consistent with the predicted benefit of reproductive synchrony on reproductive success. In addition, at the individual level we found a higher conversion of unfertilized female conelets into mature female cones during a mast year compared to a non-mast year. Collectively, parallel results at the population and individual tree level provide robust evidence for the ecological, and potentially also evolutionary, benefits of masting through increased pollination efficiency.

  15. Significant Increase in Salivary Substance P Level after a Single Oral Dose of Cevimeline in Humans

    PubMed Central

    Suzuki, Yosuke; Itoh, Hiroki; Amada, Kohei; Yamamura, Ryota; Sato, Yuhki; Takeyama, Masaharu

    2013-01-01

    Cevimeline is a novel muscarinic acetylcholine receptor agonist currently being developed as a therapeutic agent for xerostomia. We examined the effects of cevimeline on salivary and plasma levels of substance-P- (SP-), calcitonin-gene-related-peptide- (CGRP-), and vasoactive-intestinal-polypeptide- (VIP-) like immunoreactive substances (ISs) in humans. An open-labeled crossover study was conducted on seven healthy volunteers. Saliva volume was measured, and saliva and venous blood samples were collected before and 30–240 min after a single oral dose of cevimeline or placebo. Salivary and plasma levels of SP-, CGRP-, and VIP-IS were measured using a highly sensitive enzyme immunoassay. A single oral dose of cevimeline resulted in significant increases in salivary but not plasma SP-IS level compared to placebo. Cevimeline administration did not alter the salivary or plasma levels of CGRP-IS or VIP-IS compared to placebo. Significant increases in salivary volume were observed after cevimeline administration compared to placebo. A significant correlation was observed between the total release of SP-IS and that of salivary volume. These findings suggest an association of SP with the enhancement of salivary secretion by cevimeline. PMID:23589717

  16. Increased spinal cord NGF levels in rats with cobalamin (vitamin B12) deficiency.

    PubMed

    Scalabrino, Giuseppe; Mutti, Elena; Veber, Daniela; Aloe, Luigi; Corsi, Massimiliano M; Galbiati, Stefania; Tredici, Giovanni

    2006-03-27

    We have recently demonstrated that the neuropathological morphological alterations caused by cobalamin (Cbl) deficiency in the rat central nervous system are related to the vitamin's inability to modulate the synthesis of some neurotoxic and neurotrophic agents in opposite directions. In the present study, we measured nerve growth factor (NGF) levels in the spinal cord (SC) and cerebrospinal fluid (CSF) of rats made Cbl-deficient (Cbl-D) by means of total gastrectomy (TG) or a Cbl-D diet. In both cases, Cbl deficiency increased SC and CSF NGF levels after the appearance of myelinolytic lesions in the SC white matter (SCWM) (i.e. after the second post-TG month), and these changes were normalised by Cbl treatment in the 4-month-totally-gastrectomised (TGX) rats. Intracerebroventricular (i.c.v.) anti-NGF-antibody treatment prevented the onset of the myelinolytic SCWM lesions in the 2-month-TGX rats (i.e. when SC and CSF NGF levels are still normal) and normalised the ultrastructure of the SCWM in the 4-month-TGX rats, which was however worsened by the i.c.v. administration of NGF. These findings demonstrate that: (i) Cbl deficiency increases SC and CSF NGF levels; and (ii) endogenous NGF seems to play a noxious role in the progression of rat Cbl-D central neuropathy.

  17. Paternal retrievals increase testosterone levels in both male and female California mouse (Peromyscus californicus) offspring.

    PubMed

    Chary, Mamatha C; Cruz, Jayson P; Bardi, Massimo; Becker, Elizabeth A

    2015-07-01

    The importance of maternal care on offspring development has received considerable attention, although more recently, researchers have begun to focus on the significance of paternal contributions. In the monogamous and bi-parental California mouse, fathers provide high levels of care, and therefore serve as a model system for studying paternal effects on behavior and underlying neuroendocrine mechanisms. Paternal retrievals in this species influence long term changes in brain (expression of arginine vasopressin-AVP) and behavior (aggression and parenting) in adult male offspring. Further, paternal retrievals induce a transient increase in testosterone (T) in male offspring, which is thought to mediate the relationship between paternal retrievals and AVP expression. Although the father-son relationship has been well characterized, few studies have examined father-daughter interactions. In California mice, paternal retrievals increase aggression in female offspring. Although T has been implicated in the regulation of female aggression, it remains unclear whether T may underlie long-term changes in female offspring aggression in response to paternal retrievals. In the current study, we examined the influence of paternal retrievals on T in both male and female offspring. Retrievals were manipulated experimentally by displacement of the pup and trunk blood was collected from retrieved, non-retrieved, and non-manipulated (baseline) pups. We found that fathers expressed similar levels of retrievals towards sons and daughters, and that T levels were elevated in retrieved, as compared to non-retrieved offspring. Similar to what has been previously described in male offspring and replicated here, female offspring that were retrieved had higher T levels than non-retrieved females. Neither females nor males experienced a change in corticosterone levels in response to retrievals suggesting offspring do not mount a stress response to paternal care. Therefore, our data suggest

  18. Sustained low abscisic acid levels increase seedling vigor under cold stress in rice (Oryza sativa L.).

    PubMed

    Mega, Ryosuke; Meguro-Maoka, Ayano; Endo, Akira; Shimosaka, Etsuo; Murayama, Seiji; Nambara, Eiji; Seo, Mitsunori; Kanno, Yuri; Abrams, Suzanne R; Sato, Yutaka

    2015-01-01

    Stress-induced abscisic acid (ABA) is mainly catabolized by ABA 8'-hydroxylase (ABA8ox), which also strictly regulates endogenous ABA levels. Although three members of the ABA8ox gene family are conserved in rice, it is not clear which stressors induce expression of these genes. Here, we found that OsABA8ox1 was induced by cold stress within 24 h and that OsABA8ox2 and OsABA8ox3 were not. In contrast, OsABA8ox2 and OsABA8ox3 were ABA-inducible, but OsABA8ox1 was not. OsABA8ox1, OsABA8ox2, and OsABA8ox3 restored germination of a cyp707a1/a2/a3 triple mutant of Arabidopsis to rates comparable to those of the wild type, indicating that OsABA8ox1, OsABA8ox2, and OsABA8ox3 function as ABA-catabolic genes in vivo. Transgenic rice lines overexpressing OsABA8ox1 showed decreased levels of ABA and increased seedling vigor at 15 °C. These results indicate that sustained low levels of ABA lead to increased seedling vigor during cold stress. On the other hand, excessively low endogenous ABA levels caused reduced drought and cold tolerance, although some of the transgenic rice lines expressing OsABA8ox1 at moderate levels did not show these harmful effects. Adequate regulation of endogenous ABA levels is thought to be crucial for maintaining seedling vigor under cold stress and for cold and drought tolerance in rice.

  19. Paternal retrievals increase testosterone levels in both male and female California mouse (Peromyscus californicus) offspring.

    PubMed

    Chary, Mamatha C; Cruz, Jayson P; Bardi, Massimo; Becker, Elizabeth A

    2015-07-01

    The importance of maternal care on offspring development has received considerable attention, although more recently, researchers have begun to focus on the significance of paternal contributions. In the monogamous and bi-parental California mouse, fathers provide high levels of care, and therefore serve as a model system for studying paternal effects on behavior and underlying neuroendocrine mechanisms. Paternal retrievals in this species influence long term changes in brain (expression of arginine vasopressin-AVP) and behavior (aggression and parenting) in adult male offspring. Further, paternal retrievals induce a transient increase in testosterone (T) in male offspring, which is thought to mediate the relationship between paternal retrievals and AVP expression. Although the father-son relationship has been well characterized, few studies have examined father-daughter interactions. In California mice, paternal retrievals increase aggression in female offspring. Although T has been implicated in the regulation of female aggression, it remains unclear whether T may underlie long-term changes in female offspring aggression in response to paternal retrievals. In the current study, we examined the influence of paternal retrievals on T in both male and female offspring. Retrievals were manipulated experimentally by displacement of the pup and trunk blood was collected from retrieved, non-retrieved, and non-manipulated (baseline) pups. We found that fathers expressed similar levels of retrievals towards sons and daughters, and that T levels were elevated in retrieved, as compared to non-retrieved offspring. Similar to what has been previously described in male offspring and replicated here, female offspring that were retrieved had higher T levels than non-retrieved females. Neither females nor males experienced a change in corticosterone levels in response to retrievals suggesting offspring do not mount a stress response to paternal care. Therefore, our data suggest

  20. Pesticide exposure in honey bees results in increased levels of the gut pathogen Nosema.

    PubMed

    Pettis, Jeffery S; vanEngelsdorp, Dennis; Johnson, Josephine; Dively, Galen

    2012-02-01

    Global pollinator declines have been attributed to habitat destruction, pesticide use, and climate change or some combination of these factors, and managed honey bees, Apis mellifera, are part of worldwide pollinator declines. Here we exposed honey bee colonies during three brood generations to sub-lethal doses of a widely used pesticide, imidacloprid, and then subsequently challenged newly emerged bees with the gut parasite, Nosema spp. The pesticide dosages used were below levels demonstrated to cause effects on longevity or foraging in adult honey bees. Nosema infections increased significantly in the bees from pesticide-treated hives when compared to bees from control hives demonstrating an indirect effect of pesticides on pathogen growth in honey bees. We clearly demonstrate an increase in pathogen growth within individual bees reared in colonies exposed to one of the most widely used pesticides worldwide, imidacloprid, at below levels considered harmful to bees. The finding that individual bees with undetectable levels of the target pesticide, after being reared in a sub-lethal pesticide environment within the colony, had higher Nosema is significant. Interactions between pesticides and pathogens could be a major contributor to increased mortality of honey bee colonies, including colony collapse disorder, and other pollinator declines worldwide.

  1. Pesticide exposure in honey bees results in increased levels of the gut pathogen Nosema

    NASA Astrophysics Data System (ADS)

    Pettis, Jeffery S.; Vanengelsdorp, Dennis; Johnson, Josephine; Dively, Galen

    2012-02-01

    Global pollinator declines have been attributed to habitat destruction, pesticide use, and climate change or some combination of these factors, and managed honey bees, Apis mellifera, are part of worldwide pollinator declines. Here we exposed honey bee colonies during three brood generations to sub-lethal doses of a widely used pesticide, imidacloprid, and then subsequently challenged newly emerged bees with the gut parasite, Nosema spp. The pesticide dosages used were below levels demonstrated to cause effects on longevity or foraging in adult honey bees. Nosema infections increased significantly in the bees from pesticide-treated hives when compared to bees from control hives demonstrating an indirect effect of pesticides on pathogen growth in honey bees. We clearly demonstrate an increase in pathogen growth within individual bees reared in colonies exposed to one of the most widely used pesticides worldwide, imidacloprid, at below levels considered harmful to bees. The finding that individual bees with undetectable levels of the target pesticide, after being reared in a sub-lethal pesticide environment within the colony, had higher Nosema is significant. Interactions between pesticides and pathogens could be a major contributor to increased mortality of honey bee colonies, including colony collapse disorder, and other pollinator declines worldwide.

  2. Comparing Canadian and American cybersecurity awareness levels: Educational strategies to increase public awareness

    NASA Astrophysics Data System (ADS)

    Hoggard, Amy

    Cybersecurity awareness is an important issue that affects everyone who uses a computer or a mobile device. Canada and the United States both recognize the value of mitigating cybersecurity risks in terms of national safety, economic stability and protection of their citizens. The research performed compared the levels of cybersecurity awareness in Canadian and American Internet users. Canadian and American users were equally aware of cybersecurity measures, but were not implementing best practices to keep themselves safe. The research suggested users needed to understand why a cybersecurity measure was important before being motivated to implement it. Educational strategies were reviewed in both Canada and the United States and it was determined that although there were significant resources available, they were not being utilized by both the educators and the public. In order to increase cybersecurity awareness levels, nations should focus on increasing the public's awareness by using various types of messaging, such as cartoons, in media. One possible consideration is a compulsory awareness model before accessing the Internet. Cybersecurity topics should be included in the curriculum for students at all levels of education and a focus on providing training and resources to teachers will help increase the cybersecurity knowledge of children and youth.

  3. Drought-Induced Increases in Abscisic Acid Levels in the Root Apex of Sunflower 1

    PubMed Central

    Robertson, J. Mason; Pharis, Richard P.; Huang, Yan Y.; Reid, David M.; Yeung, Edward C.

    1985-01-01

    Abscisic acid (ABA) levels in 3-mm apical root segments of slowly droughted sunflower plants (Helianthus annuus L. cv Russian Giant) were analyzed as the methyl ester by selected ion monitoring gas chromatography-mass spectrometry using characteristic ions. An internal standard, hexadeuterated ABA (d6ABA) was used for quantitative analysis. Sunflower seedlings, grown in aeroponic chambers, were slowly droughted over a 7-day period. Drought stress increased ABA levels in the root tips at 24, 72, and 168 hour sample times. Control plants had 57 to 106 nanograms per gram ABA dry weight in the root tips (leaf water potential, −0.35 to −0.42 megapascals). The greatest increase in ABA, about 20-fold, was found after 72 hours of drought (leaf water potential, −1.34 to −1.47 megapascals). Levels of ABA also increased (about 7− to 54-fold) in 3-mm apical root segments which were excised and then allowed to dessicate for 1 hour at room temperature. PMID:16664535

  4. Social challenge increases cortisol and hypothalamic monoamine levels in matrinxã (Brycon amazonicus).

    PubMed

    Wolkers, Carla Patrícia Bejo; Serra, Mônica; Urbinati, Elisabeth Criscuolo

    2015-12-01

    The neural circuitry for social behavior and aggression appears to be evolutionarily conserved across the vertebrate subphylum and involves a complex neural network that includes the hypothalamus as a key structure. In the present study, we evaluated the changes in monoamine levels in the hypothalamus and on serum cortisol and plasma glucose of resident matrinxã (Brycon amazonicus) submitted to a social challenge (introduction of an intruder in their territory). The fight promoted a significant increase in hypothalamic 5-HT, NA and DA levels and on the metabolites 5-HIAA and DOPAC, and decreased 5-HIAA/5-HT and DOPAC/DA ratios in resident fish. Furthermore, an increase in serum cortisol and plasma glucose was also observed after the fight. Resident fish presented a high aggressiveness even with increased 5-HT levels in the hypothalamus. The alteration in hypothalamic monoaminergic activity of matrinxã suggests that this diencephalic region is involved in aggression and stress modulation in fish; however, it does not exclude the participation of other brain areas not tested here. PMID:26205527

  5. Population level policy options for increasing the prevalence of smokefree homes

    PubMed Central

    Thomson, George; Wilson, Nick; Howden‐Chapman, Philippa

    2006-01-01

    Objective To identify and evaluate the options for population level government policies to increase the prevalence of homes free of secondhand smoke. Methods The literature was searched for population level policy options and evidence on them. Three criteria were used to evaluate the policy options: effectiveness, the reductions on inequalities in secondhand smoke exposure, and cost effectiveness. The setting was four developed, English speaking jurisdictions: Britain, USA, Australia, and New Zealand. Results Evidence from all four countries shows some association between relatively comprehensive tobacco control programmes and lower prevalence levels of smoking in homes. The evidence of the effect of such programmes on inequalities in smokefree home prevalence is limited. No published evidence was found of the cost effectiveness of the programmes in achieving changes in smokefree homes. Within comprehensive programmes, there is some indirect evidence that some mass media campaigns could increase the prevalence of smokefree homes. Structural options that have potential to support smokefree homes include smokefree places legislation, and laws for the protection of children. Conclusion The available evidence to date suggests that comprehensive tobacco control programmes (to reduce the prevalence of smoking in the total population) are likely to be the most effective and sustainable option for increasing the prevalence of smokefree homes. PMID:16537345

  6. The evaluation of increase in hemodialysis frequency on C-reactive protein levels and nutritional status.

    PubMed

    Rashidi, Ali Akbar; Soleimani, Ali Reza; Nikoueinejad, Hassan; Sarbolouki, Shokooh

    2013-03-16

    Malnutrition and inflammation are the most important causes of cardiovascular disease in hemodialysis patients. This study was conducted to evaluate the effect of increase in hemodialysis frequency on C-reactive protein (CRP) level and nutritional markers in contrast to previous routine method. 18 hemodialysis patients with a mean age of 53±16 years were randomly selected in this before-and-after clinical trial. The patients under a standard hemodialysis of 3 times/4 h per week were converted to 4 times/4 h for a period of 6 weeks. The CRP, albumin, triglyceride, total cholesterol, LDL, HDL serum levels, anthropometric indices and 24-h diet recall intake was assessed before and after of the period. The data were analyzed using paired t-test, and P-value less than 0.05 was considered significant. All patients completed the study. Mean weight, body mass index and serum albumin increased while serum CRP level decreased significantly after the intervention (P<0.03). Triglyceride, total cholesterol, LDL, HDL, as well as energy, protein and fat intake had no significant change before and after the study. Increase in dialysis frequency decreased systemic inflammation and improved the nutritional state of hemodialysis patients. Therefore, it may decrease the risk of cardiovascular events in these patients.

  7. Mechanisms Underpinning Increased Plasma Creatinine Levels in Patients Receiving Vemurafenib for Advanced Melanoma

    PubMed Central

    Hurabielle, Charlotte; Pillebout, Evangéline; Stehlé, Thomas; Pagès, Cécile; Roux, Jennifer; Schneider, Pierre; Chevret, Sylvie; Chaffaut, Cendrine; Boutten, Anne; Mourah, Samia; Basset-Seguin, Nicole; Vidal-Petiot, Emmanuelle; Lebbé, Céleste; Flamant, Martin

    2016-01-01

    Context Serum creatinine has been reported to increase in patients receiving Vemurafenib, yet neither the prevalence nor the mechanism of this adverse event are known. Objective We aimed to evaluate the frequency and the mechanisms of increases in plasma creatinine level in patients receiving Vemurafenib for advanced melanoma. Methods We performed a retrospective monocentric study including consecutive patients treated with Vemurafenib for an advanced melanoma. We collected clinical and biological data concerning renal function before introduction of Vemurafenib and in the course of monthly follow-up visits from March 2013 to December 2014. Cystatin C-derived glomerular filtration rate was evaluated before and after Vemurafenib initiation, as increase in serum cystatin C is specific to a decrease in the glomerular filtration rate. We also performed thorough renal explorations in 3 patients, with measurement of tubular secretion of creatinine before and after Vemurafenib initiation and a renal biopsy in 2 patients. Results 70 patients were included: 97% of them displayed an immediate, and thereafter stable, increase in creatinine (+22.8%) after Vemurafenib initiation. In 44/52 patients in whom Vemurafenib was discontinued, creatinine levels returned to baseline. Serum cystatin C increased, although proportionally less than serum creatinine, showing that creatinine increase under vemurafenib was indeed partly due to a renal function impairment. In addition, renal explorations demonstrated that Vemurafenib induced an inhibition of creatinine tubular secretion. Conclusion Thus, Vemurafenib induces a dual mechanism of increase in plasma creatinine with both an inhibition of creatinine tubular secretion and slight renal function impairment. However, this side effect is mostly reversible when Vemurafenib is discontinued, and should not lead physicians to discontinue the treatment if it is effective. PMID:26930506

  8. Increased serum and testicular androgen levels in F1 rats with lifetime exposure to soy isoflavones.

    PubMed

    McVey, Mark J; Cooke, Gerard M; Curran, Ivan H A

    2004-07-01

    The consequences of dietary soy isoflavones on serum and testicular androgen levels were examined in F1 male rats from a multigeneration study investigating the effects of diets varying in isoflavone content. Rats were fed either a soy-free casein based diet (AIN93G) or a diet in which alcohol-washed soy protein replaced casein as the protein source and to which increasing amounts of Novasoy, a commercially available isoflavone supplement were added. Analysis of these diets showed that the isoflavone content in each diet was 0 (diet 1; casein based control), 31.7 (diet 2; alcohol-washed soy-based diet control), 36.1 (diet 3), 74.5 (diet 4), 235.6 (diet 5) and 1046.6 (diet 6) mg total isoflavones/kg pelleted diet. The levels of isoflavones in diet 1 would represent a daily intake level of 0 mg isoflavones, diets 2 and 3 estimate a low soy-containing human diet (e.g. North American), diet 4 would correspond to Asian diets (e.g. Japanese) or adult humans taking isoflavone supplements, diet 5 approximates the isoflavone intake by babies fed soy based infant formula and diet 6 approximates fivefold the intake levels by babies or 10-fold the intake levels of adults consuming high isoflavone containing diets. Serum testosterone (T) from F1 male rats sacrificed on postnatal days (PND) 28, 70, 120, 240 and 360 were low at PND 28 (0.4 ng/ml), increased approximately five to sixfold at PND 70 (2.5-3.0 ng/ml) and thereafter declined to a steady state level of approximately 1 ng/ml by PND 120. However, rats on diets 5 and 6 demonstrated altered serum testosterone profiles such that at days 120, testosterone levels remained significantly elevated at approximately 3 ng/ml (P < 0.05). Serum dihydrotestosterone levels exhibited similar profiles and the levels in PND 120 rats on diet 5 or 6 were also significantly elevated (two to threefold, P < 0.05). The intra-testicular testosterone concentration in rats on diet 5 was also elevated at PND 120 compared with diet 1 (P < 0

  9. Increased acetyl and total histone levels in post-mortem Alzheimer's disease brain.

    PubMed

    Narayan, Pritika J; Lill, Claire; Faull, Richard; Curtis, Maurice A; Dragunow, Mike

    2015-02-01

    Histone acetylation is an epigenetic modification that plays a critical role in chromatin remodelling and transcriptional regulation. There is increasing evidence that epigenetic modifications may become compromised in aging and increase susceptibility to the development of neurodegenerative disorders such as Alzheimer's disease. Immunohistochemical labelling of free-floating sections from the inferior temporal gyrus (Alzheimer's disease, n=14; control, n=17) and paraffin-embedded tissue microarrays containing tissue from the middle temporal gyrus (Alzheimer's disease, n=29; control, n=28) demonstrated that acetyl histone H3 and acetyl histone H4 levels, as well as total histone H3 and total histone H4 protein levels, were significantly increased in post-mortem Alzheimer's disease brain tissue compared to age- and sex-matched neurologically normal control brain tissue. Changes in acetyl histone levels were proportional to changes in total histone levels. The increase in acetyl histone H3 and H4 was observed in Neuronal N immunopositive pyramidal neurons in Alzheimer's disease brain. Using immunolabelling, histone markers correlated significantly with the level of glial fibrillary acidic protein and HLA-DP, -DQ and -DR immunopositive cells and with the pathological hallmarks of Alzheimer's disease (hyperphosphorylated tau load and β-amyloid plaques). Given that histone acetylation changes were correlated with changes in total histone protein, it was important to evaluate if protein degradation pathways may be compromised in Alzheimer's disease. Consequently, significant positive correlations were also found between ubiquitin load and histone modifications. The relationship between histone acetylation and ubiquitin levels was further investigated in an in vitro model of SK-N-SH cells treated with the proteasome inhibitor Mg132 and the histone deacetylase inhibitor valproic acid. In this model, compromised protein degradation caused by Mg132 lead to elevated histone

  10. Increased ischemia-modified albumin and malondialdehyde levels in videothoracoscopic surgery

    PubMed Central

    Oncel, Mufide; Kiyici, Aysel; Oncel, Murat; Sunam, Guven Sadi; Sahin, Emel; Adam, Bahattin

    2016-01-01

    BACKGROUND: Videothoracoscopic surgery leads to general organ hypoperfusion by reducing mean arterial pressure, systemic vascular resistance, and end-diastolic volume index. Oxidative stress occurs as a result of hypoperfusion. Evaluation of the short-term effects of videothoracoscopic sympathectomy on serum ischemia-modified albumin (IMA), malondialdehyde (MDA), and nitric oxide (NO) levels in patients with primary hyperhidrosis was aimed. METHODS: Twenty-six patients who underwent videothoracoscopic surgery were contributed in this study. Venous blood samples were obtained from these patients 1 h before and after the surgery. IMA, MDA, and NO levels were measured in serum samples by colorimetric methods. Albumin concentrations were also measured for each sample, and albumin-adjusted IMA levels were calculated. RESULTS: Postoperative IMA, albumin-adjusted IMA, and MDA values were significantly higher compared to the preoperative values (P = 0.003, 0.027, 0.018, respectively). However, postoperative NO levels were lower than the preoperative values (P = 0.002). There was no significant difference between pre- and postoperative albumin concentrations, and there was no significant correlation between the parameters tested. CONCLUSIONS: We can conclude that elevation in MDA and IMA levels after videothoracoscopic surgery was caused by increased oxidative stress due to minimal ischemia-reperfusion injury after the infusion of CO2 during the surgical process. Videothoracoscopic sympathectomy operation causes a decrease in NO production, and this should be taken in consideration when evaluating nitrosative stress in videothoracoscopic surgery. PMID:26933460

  11. Increased Mercury Levels in Patients with Celiac Disease following a Gluten-Free Regimen

    PubMed Central

    Elli, Luca; Rossi, Valentina; Conte, Dario; Ronchi, Anna; Tomba, Carolina; Passoni, Manuela; Bardella, Maria Teresa; Roncoroni, Leda; Guzzi, Gianpaolo

    2015-01-01

    Background and Aim. Although mercury is involved in several immunological diseases, nothing is known about its implication in celiac disease. Our aim was to evaluate blood and urinary levels of mercury in celiac patients. Methods. We prospectively enrolled 30 celiac patients (20 treated with normal duodenal mucosa and 10 untreated with duodenal atrophy) and 20 healthy controls from the same geographic area. Blood and urinary mercury concentrations were measured by means of flow injection inductively coupled plasma mass spectrometry. Enrolled patients underwent dental chart for amalgam fillings and completed a food-frequency questionnaire to evaluate diet and fish intake. Results. Mercury blood/urinary levels were 2.4 ± 2.3/1.0 ± 1.4, 10.2 ± 6.7/2.2 ± 3.0 and 3.7 ± 2.7/1.3 ± 1.2 in untreated CD, treated CD, and healthy controls, respectively. Resulting mercury levels were significantly higher in celiac patients following a gluten-free diet. No differences were found regarding fish intake and number of amalgam fillings. No demographic or clinical data were significantly associated with mercury levels in biologic samples. Conclusion. Data demonstrate a fourfold increase of mercury blood levels in celiac patients following a gluten-free diet. Further studies are needed to clarify its role in celiac mechanism. PMID:25802516

  12. Potential population-level effects of increased haulout-related mortality of Pacific walrus calves

    USGS Publications Warehouse

    Udevitz, Mark S.; Taylor, Rebecca L.; Garlich-Miller, Joel L.; Quakenbush, Lori T.; Snyder, Jonathan A.

    2013-01-01

    Availability of summer sea ice has been decreasing in the Chukchi Sea during recent decades, and increasing numbers of Pacific walruses have begun using coastal haulouts in late summer during years when sea ice retreats beyond the continental shelf. Calves and yearlings are particularly susceptible to being crushed during disturbance events that cause the herd to panic and stampede at these large haulouts, but the potential population-level effects of this mortality are unknown. We used recent harvest data, along with previous assumptions about demographic parameters for this population, to estimate female population size and structure in 2009 and project these numbers forward using a range of assumptions about future harvests and haulout-related mortality that might result from increased use of coastal haulouts during late summer. We found that if demographic parameters were held constant, the levels of harvest that occurred during 1990–2008 would have allowed the population to grow during that period. Our projections indicate, however, that an increase in haulout-related mortality affecting only calves has a greater effect on the population than an equivalent increase in harvest-related mortality distributed among all age classes. Therefore, disturbance-related mortality of calves at coastal haulouts may have relatively important population consequences.

  13. Increasing testosterone levels and effects on cognitive functions in elderly men and women: a review.

    PubMed

    Hogervorst, E; Bandelow, S; Moffat, S D

    2005-10-01

    Low testosterone (T) levels may predispose to Alzheimer disease (AD), but it is unclear whether this is a co-morbid effect due to cachexia, subclinical hyperthyroidism or other co-morbidity. The biological plausibility for potential protective effects of T on brain functions is substantial. In addition, higher levels of gonadotropins found in older cases with AD suggest that low levels of T are not due to brain degeneration and that the hypothalamic-pituitary-gonadal (HPG) axis is still intact. Men genetically at risk for AD were also already found to have lower levels of T. However, despite having lower levels of T, women do not show accelerated cognitive decline with age when compared to men. In addition, castration has not necessarily shown a decline in cognitive functions; some studies even found improvement of memory recall. Age may be an important factor when assessing optimal levels of T and several studies suggest that free or bioavailable T may be a better marker than total T levels when investigating associations of androgen activity with cognitive function. Small-scale T intervention trials in elderly men with and without dementia suggest that some cognitive deficits may be reversed, at least in part, by short term T supplementation. Age and prior hypogonadism may play an important role in therapy success and these factors should be investigated in more detail in future large scale randomized controlled studies. For elderly women, T treatment does not seem to have additional benefits over estrogen treatment for postmenopausal complaints and cognitive decline and may increase cardiovascular disease.

  14. Increased HDL cholesterol levels in mice with XX versus XY sex chromosomes

    PubMed Central

    Link, Jenny C.; Chen, Xuqi; Prien, Christopher; Borja, Mark S.; Hammerson, Bradley; Oda, Michael N.; Arnold, Arthur P.; Reue, Karen

    2015-01-01

    Objective The molecular mechanisms underlying sex differences in dyslipidemia are poorly understood. We aimed to distinguish genetic and hormonal regulators of sex differences in plasma lipid levels. Approach and Results We assessed the role of gonadal hormones and sex chromosome complement on lipid levels using the Four Core Genotypes mouse model (XX females, XX males, XY females, and XY males). In gonadally intact mice fed a chow diet, lipid levels were influenced by both male–female gonadal sex and XX–XY chromosome complement. Gonadectomy of adult mice revealed that the male–female differences are dependent on acute effects of gonadal hormones. In both intact and gonadectomized animals, XX mice had higher HDL cholesterol (HDL-C) levels than XY mice, regardless of male–female sex. Feeding a cholesterol-enriched diet produced distinct patterns of sex differences in lipid levels compared to a chow diet, revealing the interaction of gonadal and chromosomal sex with diet. Notably, under all dietary and gonadal conditions, HDL-C levels were higher in mice with two X chromosomes compared to mice with an X and Y chromosome. By generating mice with XX, XY and XXY chromosome complements, we determined that the presence of two X chromosomes, and not the absence of the Y chromosome, influences HDL-C concentration. Conclusions We demonstrate that having two X chromosomes versus an X and Y chromosome complement drives sex differences in HDL-C. It is conceivable that increased expression of genes escaping X-inactivation in XX mice regulates downstream processes to establish sexual dimorphism in plasma lipid levels. PMID:26112012

  15. Collagen cross-link excretion during space flight and bed rest

    NASA Technical Reports Server (NTRS)

    Smith, S. M.; Nillen, J. L.; Leblanc, A.; Lipton, A.; Demers, L. M.; Lane, H. W.; Leach, C. S.; LeBlanc, A. (Principal Investigator)

    1998-01-01

    Extended exposure to weightlessness results in bone loss. However, little information exists as to the precise nature or time course of this bone loss. Bone resorption results in the release of collagen breakdown products, including N-telopeptide and the pyridinium (PYD) cross-links, pyridinoline and deoxypyridinoline. Urinary pyridinoline and deoxypyridinoline are known to increase during bed rest. We assessed excretion of PYD cross-links and N-telopeptide before, during, and after long (28-day, 59-day, and 84-day) Skylab missions, as well as during short (14-day) and long (119-day) bed-rest studies. During space flight, the urinary cross-link excretion level was twice those observed before flight. Urinary excretion levels of the collagen breakdown products were also 40-50% higher, during short and long bed rest, than before. These results clearly show that the changes in bone metabolism associated with space flight involve increased resorption. The rate of response (i.e. within days to weeks) suggests that alterations in bone metabolism are an early effect of weightlessness. These studies are important for a better understanding of bone metabolism in space crews and in those who are bedridden.

  16. Ocean acidification increases the accumulation of toxic phenolic compounds across trophic levels

    PubMed Central

    Jin, Peng; Wang, Tifeng; Liu, Nana; Dupont, Sam; Beardall, John; Boyd, Philip W.; Riebesell, Ulf; Gao, Kunshan

    2015-01-01

    Increasing atmospheric CO2 concentrations are causing ocean acidification (OA), altering carbonate chemistry with consequences for marine organisms. Here we show that OA increases by 46–212% the production of phenolic compounds in phytoplankton grown under the elevated CO2 concentrations projected for the end of this century, compared with the ambient CO2 level. At the same time, mitochondrial respiration rate is enhanced under elevated CO2 concentrations by 130–160% in a single species or mixed phytoplankton assemblage. When fed with phytoplankton cells grown under OA, zooplankton assemblages have significantly higher phenolic compound content, by about 28–48%. The functional consequences of the increased accumulation of toxic phenolic compounds in primary and secondary producers have the potential to have profound consequences for marine ecosystem and seafood quality, with the possibility that fishery industries could be influenced as a result of progressive ocean changes. PMID:26503801

  17. Ocean acidification increases the accumulation of toxic phenolic compounds across trophic levels.

    PubMed

    Jin, Peng; Wang, Tifeng; Liu, Nana; Dupont, Sam; Beardall, John; Boyd, Philip W; Riebesell, Ulf; Gao, Kunshan

    2015-10-27

    Increasing atmospheric CO2 concentrations are causing ocean acidification (OA), altering carbonate chemistry with consequences for marine organisms. Here we show that OA increases by 46-212% the production of phenolic compounds in phytoplankton grown under the elevated CO2 concentrations projected for the end of this century, compared with the ambient CO2 level. At the same time, mitochondrial respiration rate is enhanced under elevated CO2 concentrations by 130-160% in a single species or mixed phytoplankton assemblage. When fed with phytoplankton cells grown under OA, zooplankton assemblages have significantly higher phenolic compound content, by about 28-48%. The functional consequences of the increased accumulation of toxic phenolic compounds in primary and secondary producers have the potential to have profound consequences for marine ecosystem and seafood quality, with the possibility that fishery industries could be influenced as a result of progressive ocean changes.

  18. Ocean acidification increases the accumulation of toxic phenolic compounds across trophic levels

    NASA Astrophysics Data System (ADS)

    Jin, Peng; Wang, Tifeng; Liu, Nana; Dupont, Sam; Beardall, John; Boyd, Philip W.; Riebesell, Ulf; Gao, Kunshan

    2015-10-01

    Increasing atmospheric CO2 concentrations are causing ocean acidification (OA), altering carbonate chemistry with consequences for marine organisms. Here we show that OA increases by 46-212% the production of phenolic compounds in phytoplankton grown under the elevated CO2 concentrations projected for the end of this century, compared with the ambient CO2 level. At the same time, mitochondrial respiration rate is enhanced under elevated CO2 concentrations by 130-160% in a single species or mixed phytoplankton assemblage. When fed with phytoplankton cells grown under OA, zooplankton assemblages have significantly higher phenolic compound content, by about 28-48%. The functional consequences of the increased accumulation of toxic phenolic compounds in primary and secondary producers have the potential to have profound consequences for marine ecosystem and seafood quality, with the possibility that fishery industries could be influenced as a result of progressive ocean changes.

  19. Sea-level Rise Increases the Frequency of Nuisance Flooding in Coastal Regions

    NASA Astrophysics Data System (ADS)

    Moftakhari Rostamkhani, H.; Aghakouchak, A.; Sanders, B. F.; Feldman, D.; Sweet, W.; Matthew, R.; Luke, A.

    2015-12-01

    The global warming-drivensea-level rise (SLR) posesa serious threat for population and assets in flood-prone coastal zones over the next century. The rate of SLR is accelerated in recent decades and is expected to increase based on current trajectories of anthropogenic activities and greenhouse gas emissions. Over the 20th century, an increase in the frequency of nuisance (minor) flooding has been reported due to the reduced gap between tidal datum and flood stage. Nuisance flooding (NF), however non-destructive, causes public inconvenience, business interruption, and substantial economic losses due to impacts such as road closures and degradation of infrastructure. It also portends an increased risk in severe floods. Here we report substantial increases in NF along the coasts of United States due to SLR over the past decades. We then take the projected SLR under the least and the most extreme representative concentration pathways (e.gRCP2.6 and RCP 8.5) to estimate the increase in NF in the near- (2030) and mid-term (2050) future. The results suggest that projected SLR will cause up to two-fold more frequent NF by 2050, compared with the 20th century. The projected increase in NF will have significant socio-economic impacts and pose public health risks especially in rapidly urbanized coastal regions.

  20. TBT-induced imposex in marine neogastropods is mediated by an increasing androgen level

    NASA Astrophysics Data System (ADS)

    Bettin, C.; Oehlmann, J.; Stroben, E.

    1996-09-01

    Tributyltin (TBT) exposure at different concentrations (5, 60, and 100 ng TBT as Sn/l) induces a concentration- and time-dependent imposex (=pseudohermaphroditism) development in female Nucella lapillus and Hinia reticulata. In both species the average imposex stage, termed as vas deferens sequence (VDS) index, and the average female penis length increases with increasing TBT concentration and duration of TBT exposure. Testosterone added at a concentration of 500 ng/l induces a faster and more intensive imposex development compared to that induced by the TBT concentrations used in the present experiments. Radioimmunological determination of endogenous steroid content reveals increasing testosterone titres in female gastropods exposed to TBT which correlate with the TBT concentration used and the duration of the experiment. The most marked and highest increase of the endogenous testosterone level is exhibited by females, of both species exposed to testosterone. Simulataneous exposure to TBT and to the antiandrogen cyproterone acetate which suppresses imposex development completely in N. lapillus and reduces imposex development strongly in H. reticulata proves that the imposex-inducing effects of TBT are mediated by an increasing androgen level and are not caused directly by the organotin compound itself. Further-more, TBT-induced imposex development can be suppressed in both snails by adding estrogens to the aqueous medium. These observations suggest that TBT causes an inhibition of the cytochrome P-450 dependent aromatase system which catalyses the aromatization of androgens to estrogens. The increase of the androgen content or the shift of the androgen-estrogen balance in favour of androgens induces the development of pseudohermaphroditism in marine prosobranchs. Artificial inhibition of the cytochrome P-450 dependent aromatase system using SH 489 (1-methyl-1,4-androstadiene-3,17-dione) as a steroidal aromatase inhibitor and flavone as a nonsteroidal aromatase

  1. Sympathetic arousal increases a negative memory bias in young women with low sex hormone levels.

    PubMed

    Nielsen, Shawn E; Barber, Sarah J; Chai, Audrey; Clewett, David V; Mather, Mara

    2015-12-01

    Emotionally arousing events are typically better attended to and remembered than neutral ones. Current theories propose that arousal-induced increases in norepinephrine during encoding bias attention and memory in favor of affectively salient stimuli. Here, we tested this hypothesis by manipulating levels of physiological arousal prior to encoding and examining how it influenced memory for emotionally salient images, particularly those that are negative rather than positive in valence. We also tested whether sex steroid hormones interact with noradrenergic activity to influence these emotional memory biases in women. Healthy naturally cycling women and women on hormonal contraception completed one of the following physiological arousal manipulations prior to viewing a series of negative, positive and neutral images: (1) immediate handgrip arousal-isometric handgrip immediately prior to encoding, (2) residual handgrip arousal-isometric handgrip 15min prior to encoding, or (3) no handgrip. Sympathetic arousal was measured throughout the session via pupil diameter changes. Levels of 17β-estradiol and progesterone were measured via salivary samples. Memory performance was assessed approximately 10min after encoding using a surprise free recall test. The results indicated that handgrip successfully increased sympathetic arousal compared to the control task. Under immediate handgrip arousal, women showed enhanced memory for negative images over positive images; this pattern was not observed in women assigned to the residual and no-handgrip arousal conditions. Additionally, under immediate handgrip arousal, both high estradiol and progesterone levels attenuated the memory bias for negative over positive images. Follow-up hierarchical linear models revealed consistent effects when accounting for trial-by-trial variability in normative International Affective Picture System valence and arousal ratings. These findings suggest that heightened sympathetic arousal interacts

  2. Increased levels of bacterial markers and CO2 in occupied school rooms.

    PubMed

    Fox, Alvin; Harley, William; Feigley, Charles; Salzberg, Deborah; Sebastian, Aleksandra; Larsson, Lennart

    2003-04-01

    Our group previously demonstrated that carbon dioxide (CO2) levels in heavily occupied schools correlate with the levels of airborne bacterial markers. Since CO2 is derived from the room occupants, it was hypothesized that in schools, bacterial markers may be primarily increased in indoor air because of the presence of children; directly from skin microflora or indirectly, by stirring up dust from carpets and other sources. The purpose of this project was to test the hypothesis. Muramic acid (Mur) is found in almost all bacteria whereas 3-hydroxy fatty acids (3-OH FAs) are found only in Gram-negative bacteria. Thus Mur and 3-OH FA serve as markers to assess bacterial levels in indoor air (pmol m(-3)). In our previous school studies, airborne dust was collected only from occupied rooms. However, in the present study, additional dust samples were collected from the same rooms each weekend when unoccupied. Samples were also collected from outside air. The levels of dust, Mur and C10:0, C12:0, C14:0, and C16:0 3-OH FAs were each much higher (range 5-50 fold) in occupied rooms than in unoccupied school rooms. Levels in outdoor air were much lower than that of indoor air from occupied classrooms and higher than the levels in the same rooms when unoccupied. The mean CO2 concentrations were around 420 parts per million (ppm) in unoccupied rooms and outside air; and they ranged from 1017 to 1736 ppm in occupied rooms, regularly exceeding 800-1000 ppm, which are the maximum levels indicative of adequate indoor ventilation. This indicates that the children were responsible for the increased levels of bacterial markers. However, the concentration of Mur in dust was also 6 fold higher in occupied rooms (115.5 versus 18.2 pmole mg(-1)). This further suggests that airborne dust present in occupied and unoccupied rooms is quite distinct. In conclusion in unoccupied rooms, the dust was of environmental origin but the children were the primary source in occupied rooms.

  3. Novel psychoactive benzofurans strongly increase extracellular serotonin level in mouse corpus striatum.

    PubMed

    Fuwa, Tatsu; Suzuki, Jin; Tanaka, Toyohito; Inomata, Akiko; Honda, Yoshiko; Kodama, Tohru

    2016-01-01

    We examined the effects of three benzofurans [1-(Benzofuran-5-yl)-N-methylpropan-2-amine (5-MAPB), 1-(Benzofuran-2-yl)-N-methylpropan-2-amine (2-MAPB), and 1-(Benzofuran-5-yl)-N-ethylpropan-2-amine (5-EAPB)] on the extracellular monoamine level in mouse corpus striatum by the microdialysis method and compared them with the effects of psychoactive 3,4-Methylenedioxymethamphetamine (MDMA). The effects of benzofurans on the extracellular monoamine level were qualitatively analogous to that of MDMA, with an increase in serotonin (5-HT) level exceeding dopamine (DA) level. The effects of 2-MAPB and 5-EAPB were almost the same as the effect of MDMA. However, 5-MAPB strongly increased extracellular monoamine level than MDMA. These differences in the potency appear to have a structure-activity relationship. The administration of 5-MAPB (1.6 × 10(-4) mol/kg B.W.) resulted in the death of two-thirds of the mice. The same dose of MDMA did not cause any deaths. The administration of 5-MAPB (1.6 × 10(-4) mol/kg B.W.) produced a 3.41°C ± 0.28°C rise in rectal temperature after 1 hr, whereas the administration of MDMA (1.6 × 10(-4) mol/kg B.W.) produced an approximate 1.85°C ± 0.26°C rise. These results suggest that benzofurans have 5-HT toxicity similar to MDMA, and 5-MAPB has a higher risk of lethal intoxication than MDMA. Furthermore, 5-APB, the metabolic product of 5-MAPB demethylation, may be involved in the acute 5-HT toxicity and may cause lethal intoxication in mice. PMID:27193726

  4. Increased Future Sea Level Rise due to Rapid Decay of the Greenland Ice Sheet?

    NASA Astrophysics Data System (ADS)

    Greve, R.

    2008-12-01

    In the Fourth Assessment Report (AR4) of the United Nations Intergovernmental Panel on Climate Change (IPCC), an increase of the mean global sea level by 18-59 cm for the 21st century is projected for the six SRES marker scenarios B1, B2, A1B, A1T, A2 and A1FI. The main causes for this sea level rise are thermal expansion of sea water and melting of glaciers and small ice caps, and to a lesser extent changes of the surface mass balance of the Greenland and Antarctic ice sheets. However, recent observations suggest that ice flow dynamics could lead to additional sea level rise, and this problem is explicitly stated in the AR4. These conjectured dynamical processes are (i) surface-meltwater-induced acceleration of basal sliding, and (ii) increased ice discharge due to reduced buttressing from surrounding ice shelves. The former process is probably more relevant for the Greenland ice sheet, whereas the latter may affect the stability of the West Antarctic ice sheet. On the observational side, recent results from satellite gravity measurements for the period 2002-2005 indicate surprisingly large mass losses of 239±23 km3 a-1 (0.66± 0.06 mm a-1 sea level equivalent) for the Greenland ice sheet. Furthermore, major outlet glaciers (Jacobshavn ice stream, Kangerdlugssuaq and Helheim glaciers) have sped up drastically during the last 15 years. It is attempted to quantify the range of uncertainty of future sea level rise due to dynamical processes of the Greenland ice sheet by numerical simulations with a high-resolution version of the 3-D dynamic/thermodynamic model SICOPOLIS. Results suggest that ice-dynamical processes can speed up the decay of the Greenland ice sheet significantly, but not catastrophically, in the 21st century and beyond.

  5. Effect of glucose content on thermally cross-linked fibrous gelatin scaffolds for tissue engineering.

    PubMed

    Siimon, Kaido; Reemann, Paula; Põder, Annika; Pook, Martin; Kangur, Triin; Kingo, Külli; Jaks, Viljar; Mäeorg, Uno; Järvekülg, Martin

    2014-09-01

    Thermally cross-linked glucose-containing electrospun gelatin meshes were studied as possible cell substrate materials. FTIR analysis was used to study the effect of glucose on cross-linking reactions. It was found that the presence of glucose increases the extent of cross-linking of fibrous gelatin scaffolds, which in return determines scaffold properties and their usability in tissue engineering applications. Easy to handle fabric-like scaffolds were obtained from blends containing up to 15% glucose. Maximum extent of cross-linking was reached at nearly 20% glucose content. Cross-linking effectively resulted in decreased solubility and increased resistance to enzymatic degradation. Preliminary short-term cell culture experiments indicate that such thermally cross-linked gelatin-glucose scaffolds are suitable for tissue engineering applications. PMID:25063151

  6. Oral supplementation with whey proteins increases plasma glutathione levels of HIV-infected patients.

    PubMed

    Micke, P; Beeh, K M; Schlaak, J F; Buhl, R

    2001-02-01

    HIV infection is characterized by an enhanced oxidant burden and a systemic deficiency of the tripeptide glutathione (GSH), a major antioxidant. The semi-essential amino acid cysteine is the main source of the free sulfhydryl group of GSH and limits its synthesis. Therefore, different strategies to supplement cysteine supply have been suggested to increase glutathione levels in HIV-infected individuals. The aim of this study was to evaluate the effect of oral supplementation with two different cysteine-rich whey protein formulas on plasma GSH levels and parameters of oxidative stress and immune status in HIV-infected patients. In a prospective double blind clinical trial, 30 patients (25 male, 5 female; mean age (+/- SD) 42 +/- 9.8 years) with stable HIV infection (221 +/- 102 CD4 + lymphocytes L-1) were randomized to a supplemental diet with a daily dose of 45 g whey proteins of either Protectamin (Fresenius Kabi, Bad Hamburg, Germany) or Immunocal (Immunotec, Vandreuil, Canada) for two weeks. Plasma concentrations of total, reduced and oxidized GSH, superoxide anion (O2-) release by blood mononuclear cells, plasma levels of TNF-alpha and interleukins 2 and 12 were quantified with standard methods at baseline and after therapy. Pre-therapy, plasma GSH levels (Protectamin: 1.92 +/- 0.6 microM; Immunocal: 1.98 +/- 0.9 microM) were less than normal (2.64 +/- 0.7 microM, P = 0.03). Following two weeks of oral supplementation with whey proteins, plasma GSH levels increased in the Protectamin group by 44 +/- 56% (2.79 +/- 1.2 microM, P = 0.004) while the difference in the Immunocal group did not reach significance (+ 24.5 +/- 59%, 2.51 +/- 1.48 microM, P = 0.43). Spontaneous O2- release by blood mononuclear cells was stable (20.1 +/- 14.2 vs. 22.6 +/- 16.1 nmol h-1 10-6 cells, P = 0.52) whereas PMA-induced O2- release decreased in the Protectamin group (53.7 +/- 19 vs. 39.8 +/- 18 nmol h-1 10-6 cells, P = 0.04). Plasma concentrations of TNF-alpha and interleukins 2 and

  7. Longer-term increased cortisol levels in young people with mental health problems.

    PubMed

    Heinze, Kareen; Lin, Ashleigh; Reniers, Renate L E P; Wood, Stephen J

    2016-02-28

    Disturbance of hypothalamus-pituitary-adrenal axis activity is commonly reported in a range of mental disorders in blood, saliva and urine samples. This study aimed to look at longer-term cortisol levels and their association with clinical symptoms. Hair strands of 30 young people (16-25 years) presenting with mental health problems (Mage±SD=21±2.4, 26 females) and 28 healthy controls (HC, Mage±SD=20±2.9, 26 females) were analyzed for cortisol concentrations, representing the past 6 months prior to hair sampling. Clinical participants completed an assessment on psychiatric symptoms, functioning and lifestyle factors. All participants completed the Perceived Stress Scale. Hair cortisol concentrations representing the past 3 (but not 3-6) months were significantly increased in clinical participants compared to HC. Perceived stress in the past month was significantly higher in clinical participants compared to HC, but not significantly correlated with hair cortisol. Hair cortisol levels were not significantly associated with any other measures. Hair segment analyses revealed longer-term increased levels of cortisol in the past 3 months in early mental health problems. Further insight into the role of cortisol on the pathogenesis of mental illnesses requires longitudinal studies relating cortisol to psychopathology and progression of illness. PMID:26749569

  8. Pomegranate juice consumption increases GSH levels and reduces lipid and protein oxidation in human blood.

    PubMed

    Matthaiou, Chrysoula M; Goutzourelas, Nikolaos; Stagos, Dimitrios; Sarafoglou, Eleni; Jamurtas, Athanasios; Koulocheri, Sofia D; Haroutounian, Serkos A; Tsatsakis, Aristidis M; Kouretas, Dimitrios

    2014-11-01

    The aim of the present study was the assessment of the antioxidant effects of pomegranate juice (PJ) consumption in humans. Thus, 14 healthy volunteers consumed PJ daily for a period of 15days and the changes of oxidative stress markers in their blood were assessed at four different time points, immediately before the experiment (T1), after 15days of juice administration (T2), one (T3) and three weeks (T4) after the interruption of PJ administration. The markers studied were total antioxidant capacity (TAC), levels of malondialdehyde (MDA), and protein carbonyls (CARB) measured in plasma, as well as reduced glutathione (GSH), and catalase activity (CAT) measured in erythrocytes. The MDA was reduced by 24.4% at T3 and CARB were reduced by 19.6% and 17.7% at T2 and T3, respectively, supporting the evidence that PJ consumption enhances the antioxidant status in humans by decreasing lipid peroxidation and protein oxidation. Moreover, GSH levels were significantly increased (22.6%) at T2, indicating that PJ consumption improves the antioxidant mechanisms in erythrocytes by increasing GSH levels. Finally, it was shown that even a week after stopping PJ consumption some of its beneficial effects on antioxidant status still remained in the organism.

  9. Sex steroid levels temporarily increase in response to acute psychosocial stress in healthy men and women.

    PubMed

    Lennartsson, Anna-Karin; Kushnir, Mark M; Bergquist, Jonas; Billig, Håkan; Jonsdottir, Ingibjörg H

    2012-06-01

    It is well known that acute psychosocial stress activates the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS). However, the effect of acute psychosocial stress on the hypothalamic-pituitary-gonadal (HPG) axis and levels of sex steroids are less known. The aim of this study was to investigate the effect of acute psychosocial stress on serum concentrations of sex steroids in healthy men and women. Twenty men and 19 women (age 30-50 years) underwent Trier Social Stress Test (TSST), a tool for investigating psychobiological stress responses in a laboratory setting. Blood samples were collected before, directly after the stress test, and after 30 min of recovery. Concentrations of androgens were measured with high specificity LC-MS/MS method; concentrations of cortisol, estradiol and sex hormone-binding globulin were determined using immunoassays. In both men and women we observed significantly elevated levels of testosterone, estradiol, androstenedione and sex hormone binding globulin along with significantly increased adrenocorticotropic hormone (ACTH), serum cortisol, heart rate, systolic blood pressure (SBP), and diastolic blood pressure (DBP) as a response to the stressor. Thus, even though the HPG axis and the production of sex steroids may be inhibited during prolonged periods of stress, the sex steroid levels may increase in the initial phase of acute psychosocial stress.

  10. Increased levels of lysosomal cysteinyl cathepsins in human varicose veins: a histology study.

    PubMed

    Xu, Na; Zhang, Yuan-Yuan; Lin, Yan; Bao, Bin; Zheng, Lei; Shi, Guo-Ping; Liu, Jian

    2014-02-01

    Varicose veins are a major chronic venous disease characterised by extensive remodelling of the extracellular matrix architecture in the vascular wall. Although matrix metalloproteinases have been implicated in these pathologic events, little is known about the functional relevance of other protease family members. Here, we studied the distribution of lysosomal cysteine proteases, cathepsins B, L, K, and S, and their endogenous inhibitor, cystatin C, in long saphenous vein specimens from nine normal donors and 18 patients with varicose veins (VVs). Immunohistochemical analysis demonstrated increased levels of cathepsins L, K, B, and S and reduced levels of cystatin C in VVs. This imbalance between cysteinyl cathepsins and cystatin C may favour VV remodelling. To investigate the inflammatory mechanism of their expression, we examined a detailed inflammatory cell profile in VVs, including macrophages, T lymphocytes, and mast cells. Increased numbers of CD3-positive T cells and tryptase-positive mast cells were found in VVs, and enhanced levels of cysteinyl cathepsins were detected from lesion CD3-positive T cells, chymase-positive mast cells, endothelial cells, and smooth-muscle cells. Elevated cathepsins, and their co-localisation to infiltrated inflammatory cells and to vascular cells, suggest that these proteases participate in extracellular matrix degradation in response to inflammation during VV pathogenesis.

  11. Plasma Lactate Levels Increase during Hyperinsulinemic Euglycemic Clamp and Oral Glucose Tolerance Test.

    PubMed

    Berhane, Feven; Fite, Alemu; Daboul, Nour; Al-Janabi, Wissam; Msallaty, Zaher; Caruso, Michael; Lewis, Monique K; Yi, Zhengping; Diamond, Michael P; Abou-Samra, Abdul-Badi; Seyoum, Berhane

    2015-01-01

    Insulin resistance, which plays a central role in the pathogenesis of type 2 diabetes (T2D), is an early indicator that heralds the occurrence of T2D. It is imperative to understand the metabolic changes that occur at the cellular level in the early stages of insulin resistance. The objective of this study was to determine the pattern of circulating lactate levels during oral glucose tolerance test (OGTT) and hyperinsulinemic euglycemic clamp (HIEC) study in normal nondiabetic subjects. Lactate and glycerol were determined every 30 minutes during OGTT and HIEC on 22 participants. Lactate progressively increased throughout the HIEC study period (P < 0.001). Participants with BMI < 30 had significantly higher mean M-values compared to those with BMI ≥ 30 at baseline (P < 0.05). This trend also continued throughout the OGTT. In addition, those with impaired glucose tolerance test (IGT) had significantly higher mean lactate levels compared to those with normal glucose tolerance (P < 0.001). In conclusion, we found that lactate increased during HIEC study, which is a state of hyperinsulinemia similar to the metabolic milieu seen during the early stages in the development of T2D. PMID:25961050

  12. Longer-term increased cortisol levels in young people with mental health problems

    PubMed Central

    Heinze, Kareen; Lin, Ashleigh; Reniers, Renate L.E.P.; Wood, Stephen J.

    2016-01-01

    Disturbance of hypothalamus–pituitary–adrenal axis activity is commonly reported in a range of mental disorders in blood, saliva and urine samples. This study aimed to look at longer-term cortisol levels and their association with clinical symptoms. Hair strands of 30 young people (16–25 years) presenting with mental health problems (Mage±SD=21±2.4, 26 females) and 28 healthy controls (HC, Mage±SD=20±2.9, 26 females) were analyzed for cortisol concentrations, representing the past 6 months prior to hair sampling. Clinical participants completed an assessment on psychiatric symptoms, functioning and lifestyle factors. All participants completed the Perceived Stress Scale. Hair cortisol concentrations representing the past 3 (but not 3–6) months were significantly increased in clinical participants compared to HC. Perceived stress in the past month was significantly higher in clinical participants compared to HC, but not significantly correlated with hair cortisol. Hair cortisol levels were not significantly associated with any other measures. Hair segment analyses revealed longer-term increased levels of cortisol in the past 3 months in early mental health problems. Further insight into the role of cortisol on the pathogenesis of mental illnesses requires longitudinal studies relating cortisol to psychopathology and progression of illness. PMID:26749569

  13. FXR agonist GW4064 increases plasma glucocorticoid levels in C57BL/6 mice.

    PubMed

    Hoekstra, Menno; van der Sluis, Ronald J; Li, Zhaosha; Oosterveer, Maaike H; Groen, Albert K; Van Berkel, Theo J C

    2012-10-15

    Since high expression of farnesoid X receptor (FXR) has been detected in glucocorticoid-producing adrenocortical cells, we evaluated the potential role of FXR in adrenal glucocorticoid production. FXR agonist GW4064 increased fasting plasma corticosterone levels (+45%; P<0.01) in C57BL/6 mice, indicative of enhanced adrenal steroidogenesis. GW4064 treatment did not affect plasma ACTH levels, adrenal weight, or adrenal expression of steroidogenic genes. Scavenger receptor BI (SR-BI) mRNA and protein expression, respectively, increased 1.9-fold (P<0.01) and 1.5-fold, which suggests a stimulated lipoprotein-associated cholesterol uptake into the adrenals upon GW4064 treatment. In line with an enhanced flux of cellular cholesterol into the steroidogenic pathway, adrenal unesterified and esterified cholesterol stores were 21-41% decreased (P<0.01) upon GW4064 treatment. In conclusion, we have shown that the FXR agonist GW4064 stimulates plasma corticosterone levels in C57BL/6 mice. Our findings suggest a novel role for FXR in the modulation of adrenal cholesterol metabolism and glucocorticoid synthesis in mice.

  14. Increased levels of phthalates in very low birth weight infants with septicemia and bronchopulmonary dysplasia.

    PubMed

    Strømmen, Kenneth; Lyche, Jan Ludvig; Blakstad, Elin Wahl; Moltu, Sissel Jennifer; Veierød, Marit Bragelien; Almaas, Astrid Nylander; Sakhi, Amrit Kaur; Thomsen, Cathrine; Nakstad, Britt; Brække, Kristin; Rønnestad, Arild Erlend; Drevon, Christian André; Iversen, Per Ole

    2016-01-01

    Very low birth weight infants (VLBW; birth weight<1500g) are exposed to potentially harmful phthalates from medical devices during their hospital stay. We measured urinary phthalate concentrations among hospitalized VLBW infants participating in a nutritional study. Possible associations between different phthalates and birth weight (BW), septicemia and bronchopulmonary dysplasia (BPD) were evaluated. Forty-six VLBW infants were enrolled in this randomized controlled nutritional study. The intervention group (n=24) received increased quantities of energy, protein, fat, essential fatty acids and vitamin A, as compared to the control group (n=22). The concentrations of 12 urinary phthalate metabolites were measured, using high-performance liquid chromatography coupled to tandem mass spectrometry, at 3 time points during the first 5weeks of life. During this study, the levels of di (2-ethylhexyl) phthalate (DEHP) metabolites decreased, whereas an increasing trend was seen regarding metabolites of di-iso-nonyl phthalate (DiNP). Significantly higher levels of phthalate metabolites were seen in infants with lower BW and those diagnosed with late onset septicemia or BPD. A significant positive correlation between the duration of respiratory support and DEHP metabolites was observed (p≤0.01) at 2.9weeks of age. Birth weight was negatively associated with urinary phthalate metabolite concentrations. Infants with lower BW and those diagnosed with septicemia or BPD experienced prolonged exposure from medical equipment containing phthalates, with subsequent higher levels of phthalate metabolites detected. Clinical Trial Registration no.: NCT01103219.

  15. Phosphatidylserine increases IKBKAP levels in a humanized knock-in IKBKAP mouse model.

    PubMed

    Bochner, Ron; Ziv, Yael; Zeevi, David; Donyo, Maya; Abraham, Lital; Ashery-Padan, Ruth; Ast, Gil

    2013-07-15

    Familial dysautonomia (FD) is a severe neurodegenerative genetic disorder restricted to the Ashkenazi Jewish population. The most common mutation in FD patients is a T-to-C transition at position 6 of intron 20 of the IKBKAP gene. This mutation causes aberrant skipping of exon 20 in a tissue-specific manner, leading to reduction of the IκB kinase complex-associated protein (IKAP) protein in the nervous system. We established a homozygous humanized mouse strain carrying human exon 20 and its two flanking introns; the 3' intron has the transition observed in the IKBKAP gene of FD patients. Although our FD humanized mouse does not display FD symptoms, the unique, tissue-specific splicing pattern of the IKBKAP in these mice allowed us to evaluate the effect of therapies on gene expression and exon 20 splicing. The FD mice were supplemented with phosphatidylserine (PS), a safe food supplement that increases mRNA and protein levels of IKBKAP in cell lines generated from FD patients. Here we demonstrated that PS treatment increases IKBAKP mRNA and IKAP protein levels in various tissues of FD mice without affecting exon 20 inclusion levels. We also observed that genes associated with transcription regulation and developmental processes were up-regulated in the cerebrum of PS-treated mice. Thus, PS holds promise for the treatment of FD.

  16. sFas levels increase in response to cisplatin-based chemotherapy in lung cancer patients.

    PubMed

    Ulukaya, Engin; Acilan, Ceyda; Yilmaz, Meryem; Yilmaztepe-Oral, Arzu; Ari, Ferda; Zik, Berrin; Ursavas, Ahmet; Tokullugil, Asuman H

    2010-10-01

    The Fas/Fas Ligand (FasL) system and survivin have counteracting roles in cell survival. Therefore, we explored the role of circulating soluble Fas (sFas) and the tissue levels of Fas and survivin with regard to response to chemotherapy in lung cancer patients. Serum samples from 52 lung cancer patients and 54 control subjects (19 benign lung disease and 35 healthy control subjects) were collected prior to and 24 and 48 h after chemotherapy. sFas was statistically significantly higher in the cancer group than that in the control groups (p < 0.001). Baseline (before chemotherapy) sFas values showed a statistically significant inverse correlation with overall survival (r = -0.599, p < 0.001). There was a significant increase in serum sFas levels 24 h after treatment (p < 0.05). Contrarily, tissue levels of Fas and survivin were not changed following the chemotherapy (p > 0,05). In conclusion, increased sFas may be an indicator of poor outcome in lung cancer patients. However, cisplatin-based chemotherapy may not be effective via neither the Fas/FasL system nor survivin pathway. Indeed, larger sample size is required for further evaluation.

  17. Longer-term increased cortisol levels in young people with mental health problems.

    PubMed

    Heinze, Kareen; Lin, Ashleigh; Reniers, Renate L E P; Wood, Stephen J

    2016-02-28

    Disturbance of hypothalamus-pituitary-adrenal axis activity is commonly reported in a range of mental disorders in blood, saliva and urine samples. This study aimed to look at longer-term cortisol levels and their association with clinical symptoms. Hair strands of 30 young people (16-25 years) presenting with mental health problems (Mage±SD=21±2.4, 26 females) and 28 healthy controls (HC, Mage±SD=20±2.9, 26 females) were analyzed for cortisol concentrations, representing the past 6 months prior to hair sampling. Clinical participants completed an assessment on psychiatric symptoms, functioning and lifestyle factors. All participants completed the Perceived Stress Scale. Hair cortisol concentrations representing the past 3 (but not 3-6) months were significantly increased in clinical participants compared to HC. Perceived stress in the past month was significantly higher in clinical participants compared to HC, but not significantly correlated with hair cortisol. Hair cortisol levels were not significantly associated with any other measures. Hair segment analyses revealed longer-term increased levels of cortisol in the past 3 months in early mental health problems. Further insight into the role of cortisol on the pathogenesis of mental illnesses requires longitudinal studies relating cortisol to psychopathology and progression of illness.

  18. Conditioning causes an increase in glucose transporter-4 levels in mononuclear cells in sled dogs.

    PubMed

    Schnurr, Theresia M; Reynolds, Arleigh J; Gustafson, Sally J; Duffy, Lawrence K; Dunlap, Kriya L

    2014-10-01

    This study was designed to investigate the effects of physical conditioning on the expression of the insulin sensitive glucose transporter-4 protein (GLUT4) on mononuclear cells and HOMA-IR levels in dogs and compared to results reported in human skeletal muscle and the skeletal muscle of rodent models. Blood was sampled from conditioned dogs (n = 8) and sedentary dogs (n = 8). The conditioned dogs were exercised four months prior the experiment and were following a uniform training protocol, whereas the sedentary dogs were not. GLUT4 expression in mononuclear cells and plasma insulin levels were measured using commercially available enzyme-linked immunosorbent assay (ELISA). Blood glucose levels were determined using blood plasma. HOMA-IR was calculated using plasma insulin and blood glucose levels using the linear approximation formula. Our results indicate that the state of conditioning had a significant effect on the GLUT4 expression at the surface of mononuclear cells. HOMA-IR was also affected by conditioning in dogs. GLUT4 levels in mononuclear cells of sled dogs were inversely correlated with the homeostasis model assessment of insulin sensitivity. This study demonstrates that conditioning increases GLUT4 levels in mononuclear cells of sled dogs as it has been previously reported in skeletal muscle. Our results support the potential of white blood cells as a proxy tissue for studying insulin signaling and may lead to development of a minimally invasive and direct marker of insulin resistance. This may be the first report of GLUT4 in mononuclear cells in response to exercise and measured with ELISA.

  19. Increased Blood Lactate Level Deteriorates Running Economy in World Class Endurance Athletes.

    PubMed

    Hoff, Jan; Støren, Øyvind; Finstad, Arnstein; Wang, Eivind; Helgerud, Jan

    2016-05-01

    Blood lactate accumulation is associated with development of muscle fatigue and negatively correlated to endurance performance. No research has quantified the effects of lactate presence at moderate levels of lactate accumulation. The purpose of this study was to test whether 2 moderate blood lactate concentration levels affect running economy (RE) when running at the individual lactate threshold (LT). Seven male world class endurance athletes with an average V[Combining Dot Above]O2max of 80.7 ± 2.7 ml·kg·min or 5.8 ± 0.5 L·min participated in this study. After the V[Combining Dot Above]O2max test, the subjects were resting or walking and in a random order tested for RE at their LT velocity when the blood lactate level reached either 3 mmol·L or 5 mmol·L. After a new 5-minute exercising period at maximal aerobic velocity, the crossover lactate value RE testing was performed. Running economy was significantly (p ≤ 0.05) deteriorated from 0.668 ± 0.044 to 0.705 ± 0.056 ml·kg·m or 5.5% (p ≤ 0.05) for blood lactate level of 3 mmol·L compared with 5 mmol·L, respectively. Increased lactate level from 3 to 5 mmol·L is thus accompanied by deteriorated RE at LT running velocity. The deteriorated RE at moderate levels of lactate concentration emphasizes the importance of avoiding intensities above LT in the early parts of a dominantly aerobic endurance competition. It also emphasizes the importance of a high V[Combining Dot Above]O2max for aerobic endurance athletes and may partly explain the V[Combining Dot Above]O2 slow component as impaired RE.

  20. Conditioning causes an increase in Glucose Transporter-4 levels in mononuclear cells in sled dogs

    PubMed Central

    Schnurr, Theresia M.; Reynolds, Arleigh J.; Gustafson, Sally J.; Duffy, Lawrence K.; Dunlap, Kriya L.

    2014-01-01

    This study was designed to investigate the effects of physical conditioning on the expression of the insulin sensitive glucose transporter 4 protein (GLUT4) on mononuclear cells and HOMA-IR levels in dogs and compared to results reported in human skeletal muscle and the skeletal muscle of rodent models. Blood was sampled from conditioned dogs (n=8) and sedentary dogs (n=8). The conditioned dogs were exercised four months prior the experiment and were following a uniform training protocol, whereas the sedentary dogs were not. GLUT4 expression in mononuclear cells and plasma insulin levels were measured using commercially available enzyme-linked immunosorbent assay (ELISA). Blood glucose levels were determined using blood plasma. HOMA-IR was calculated using plasma insulin and blood glucose levels using the linear approximation formula. Our results indicate that the state of conditioning had a significant effect on the GLUT4 expression at the surface of mononuclear cells. HOMA-IR was also affected by conditioning in dogs. GLUT4 levels in mononuclear cells of sled dogs were inversely correlated with the homeostasis model assessment of insulin sensitivity. This study demonstrates that conditioning increases GLUT4 levels in mononuclear cells of sled dogs as it has been previously reported in skeletal muscle. Our results support the potential of white blood cells as a proxy tissue for studying insulin signaling and may lead to development of a minimally invasive and direct marker of insulin resistance. This may be the first report of GLUT4 in mononuclear cells in response to exercise and measured with ELISA. PMID:25236492

  1. Hepatoprotectant ursodeoxycholyl lysophosphatidylethanolamide increasing phosphatidylcholine levels as a potential therapy of acute liver injury.

    PubMed

    Chamulitrat, Walee; Zhang, Wujuan; Xu, Weihong; Pathil, Anita; Setchell, Kenneth; Stremmel, Wolfgang

    2012-01-01

    It has been long known that hepatic synthesis of phosphatidylcholine (PC) is depressed during acute such as carbon tetrachloride-induced liver injury. Anti-hepatotoxic properties of PC as liposomes have been recognized for treatment of acute liver damage. Ursodeoxycholate (UDCA) is a known hepatoprotectant in stabilizing cellular membrane. For therapeutic management of liver injury, we coupled UDCA with a phospholipid known as ursodeoxycholyl lysophosphatidylethanolamide (UDCA-LPE). UDCA-LPE has been shown to first-in-class hepatoprotectant being superior to UDCA or PC. It inhibits mitochondrial damage and apoptosis, elicits survival signaling pathway, and promotes regeneration of hepatocytes. We herein report that a unique contribution of UDCA-LPE in increasing concentrations of PC in vitro and in vivo. UDCA-LPE-treated hepatocytes contained significantly increased PC levels. UDCA-LPE underwent the hydrolysis to LPE which was not the precursor of the increased PC. The levels of PC in the liver and blood were increased rapidly after intraperitoneally administration UDCA-LPE, and were found to be sustained even after 24 h. Among PC synthesis genes tested, UDCA-LPE treatment of mouse hepatocytes increased transcription of CDP-diacylglycerol synthase 1 which is an enzyme catalyzing phosphatidic acid to generate intermediates for PC synthesis. Thus, UDCA-LPE as a hepatoprotectant was able to induce synthesis of protective PC which would supplement for the loss of PC occurring during acute liver injury. This property has placed UDCA-LPE as a candidate agent for therapy of acute hepatotoxicity such as acetaminophen poisoning. PMID:22363296

  2. Towards increased waste loading in high level waste glasses: Developing a better understanding of crystallization behavior

    DOE PAGESBeta

    Marra, James C.; Kim, Dong -Sang

    2014-12-18

    A number of waste components in US defense high level radioactive wastes (HLW) have proven challenging for current Joule heated ceramic melter (JCHM) operations and have limited the ability to increase waste loadings beyond already realized levels. Many of these ''troublesome'' waste species cause crystallization in the glass melt that can negatively impact product quality or have a deleterious effect on melter processing. Thus, recent efforts at US Department of Energy laboratories have focused on understanding crystallization behavior within HLW glass melts and investigating approaches to mitigate the impacts of crystallization so that increases in waste loading can be realized.more » Advanced glass formulations have been developed to highlight the unique benefits of next-generation melter technologies such as the Cold Crucible Induction Melter (CCIM). Crystal-tolerant HLW glasses have been investigated to allow sparingly soluble components such as chromium to crystallize in the melter but pass out of the melter before accumulating. The Hanford site AZ-101 tank waste composition represents a waste group that is waste loading limited primarily due to high concentrations of Fe2O3 (with higher Al2O3). Systematic glass formulation development utilizing slightly higher process temperatures and higher tolerance to spinel crystals demonstrated that an increase in waste loading of more than 20% could be achieved for this waste composition, and by extension higher loadings for wastes in the same group.« less

  3. Towards increased waste loading in high level waste glasses: Developing a better understanding of crystallization behavior

    SciTech Connect

    Marra, James C.; Kim, Dong -Sang

    2014-12-18

    A number of waste components in US defense high level radioactive wastes (HLW) have proven challenging for current Joule heated ceramic melter (JCHM) operations and have limited the ability to increase waste loadings beyond already realized levels. Many of these ''troublesome'' waste species cause crystallization in the glass melt that can negatively impact product quality or have a deleterious effect on melter processing. Thus, recent efforts at US Department of Energy laboratories have focused on understanding crystallization behavior within HLW glass melts and investigating approaches to mitigate the impacts of crystallization so that increases in waste loading can be realized. Advanced glass formulations have been developed to highlight the unique benefits of next-generation melter technologies such as the Cold Crucible Induction Melter (CCIM). Crystal-tolerant HLW glasses have been investigated to allow sparingly soluble components such as chromium to crystallize in the melter but pass out of the melter before accumulating. The Hanford site AZ-101 tank waste composition represents a waste group that is waste loading limited primarily due to high concentrations of Fe2O3 (with higher Al2O3). Systematic glass formulation development utilizing slightly higher process temperatures and higher tolerance to spinel crystals demonstrated that an increase in waste loading of more than 20% could be achieved for this waste composition, and by extension higher loadings for wastes in the same group.

  4. Overexpression of petunia chalcone isomerase in tomato results in fruit containing increased levels of flavonols.

    PubMed

    Muir, S R; Collins, G J; Robinson, S; Hughes, S; Bovy, A; Ric De Vos, C H; van Tunen, A J; Verhoeyen, M E

    2001-05-01

    Tomatoes are an excellent source of the carotenoid lycopene, a compound that is thought to be protective against prostate cancer. They also contain small amounts of flavonoids in their peel ( approximately 5-10 mg/kg fresh weight), mainly naringenin chalcone and the flavonol rutin, a quercetin glycoside. Flavonols are very potent antioxidants, and an increasing body of epidemiological data suggests that high flavonoid intake is correlated with a decreased risk for cardiovascular disease. We have upregulated flavonol biosynthesis in the tomato in order to generate fruit with increased antioxidant capacity and a wider range of potential health benefit properties. This involved transformation of tomato with the Petunia chi-a gene encoding chalcone isomerase. Resulting transgenic tomato lines produced an increase of up to 78 fold in fruit peel flavonols, mainly due to an accumulation of rutin. No gross phenotypical differences were observed between high-flavonol transgenic and control lines. The phenotype segregated with the transgene and demonstrated a stable inheritance pattern over four subsequent generations tested thus far. Whole-fruit flavonol levels in the best of these lines are similar to those found in onions, a crop with naturally high levels of flavonol compounds. Processing of high-flavonol tomatoes demonstrated that 65% of flavonols present in the fresh fruit were retained in the processed paste, supporting their potential as raw materials for tomato-based functional food products. PMID:11329019

  5. Increase in Endogenous and Exogenous Cyclic AMP Levels Inhibits Sclerotial Development in Sclerotinia sclerotiorum

    PubMed Central

    Rollins, Jeffrey A.; Dickman, Martin B.

    1998-01-01

    Growth and development of a wild-type Sclerotinia sclerotiorum isolate were examined in the presence of various pharmacological compounds to investigate signal transduction pathways that influence the development of sclerotia. Compounds known to increase endogenous cyclic AMP (cAMP) levels in other organisms by inhibiting phosphodiesterase activity (caffeine and 3-isobutyl-1-methyl xanthine) or by activating adenylate cyclase (NaF) reduced or eliminated sclerotial development in S. sclerotiorum. Growth in the presence of 5 mM caffeine correlated with increased levels of endogenous cAMP in mycelia. In addition, incorporation of cAMP into the growth medium decreased or eliminated the production of sclerotia in a concentration-dependent manner and increased the accumulation of oxalic acid. Inhibition of sclerotial development was cAMP specific, as exogenous cyclic GMP, AMP, and ATP did not influence sclerotial development. Transfer of developing cultures to cAMP-containing medium at successive time points demonstrated that cAMP inhibits development prior to or during sclerotial initiation. Together, these results indicate that cAMP plays a role in the early transition between mycelial growth and sclerotial development. PMID:9647827

  6. Overexpression of petunia chalcone isomerase in tomato results in fruit containing increased levels of flavonols.

    PubMed

    Muir, S R; Collins, G J; Robinson, S; Hughes, S; Bovy, A; Ric De Vos, C H; van Tunen, A J; Verhoeyen, M E

    2001-05-01

    Tomatoes are an excellent source of the carotenoid lycopene, a compound that is thought to be protective against prostate cancer. They also contain small amounts of flavonoids in their peel ( approximately 5-10 mg/kg fresh weight), mainly naringenin chalcone and the flavonol rutin, a quercetin glycoside. Flavonols are very potent antioxidants, and an increasing body of epidemiological data suggests that high flavonoid intake is correlated with a decreased risk for cardiovascular disease. We have upregulated flavonol biosynthesis in the tomato in order to generate fruit with increased antioxidant capacity and a wider range of potential health benefit properties. This involved transformation of tomato with the Petunia chi-a gene encoding chalcone isomerase. Resulting transgenic tomato lines produced an increase of up to 78 fold in fruit peel flavonols, mainly due to an accumulation of rutin. No gross phenotypical differences were observed between high-flavonol transgenic and control lines. The phenotype segregated with the transgene and demonstrated a stable inheritance pattern over four subsequent generations tested thus far. Whole-fruit flavonol levels in the best of these lines are similar to those found in onions, a crop with naturally high levels of flavonol compounds. Processing of high-flavonol tomatoes demonstrated that 65% of flavonols present in the fresh fruit were retained in the processed paste, supporting their potential as raw materials for tomato-based functional food products.

  7. CDF trigger final balance: Offline resolution at low level selections to fight against Tevatron increasing luminosity

    SciTech Connect

    Amerio, S.; /Padua U. /INFN, Padua

    2010-01-01

    The CDF detector at Tevatron collider is at present the most long-lasting high energy physics experiment. Since its first data taking in 1992 it has produced many results of primary importance, such as the discovery of top quark and, more recently, the observations of Bs oscillations and single-top production. None of them would have been possible without a fast and efficient trigger system. Based on a three level architecture, the CDF trigger takes decisions on simple calorimetric and tracking objects and assures both high efficiency on signal events and low dead time. It reduces the data flow rate from 2.53 MHz, the collision rate, to 150 Hz, the current limit on tape writing and is flexible enough to be easily adapted to the continuously growing instantaneous luminosity. In the last years the Tevatron instantaneous luminosity has rapidly increased and is now reaching 4 x 10{sup 32} cm{sup -2} s{sup -1}. The CDF trigger system has been widely upgraded to cope with increasing trigger rates. The upgrade result is online reconstruction of missing transverse energy, jets and tracks with a quality comparable to the offline one. Jet energy and direction can be precisely determined and tracks can be subjected to 3-D reconstruction with good resolution. These upgrades reduce high trigger rates to acceptable levels and have provided invaluable tools to increase the purity of the collected samples. They also represent a helpful experience for LHC experiments where background rates will be much more demanding.

  8. Increased low-level chromosome 21 mosaicism in older individuals with Down syndrome

    SciTech Connect

    Jenkins, E.C.; Genovese, M.; Ye, Ling Ling

    1997-01-20

    During a study of the familial aggregation of Down syndrome (DS) and Alzheimer disease (AD), we observed an increase in mosaicism for disomy 21 in older individuals with DS. In a total of 213 DS subjects who were studied cytogenetically, only 1 of 121 (0.8%) under age 45 exhibited mosaicism, while 14 of 92 (15.2%) who were age 45 or older had mosaicism. Mosaicism in this report connotes {open_quotes}low-level{close_quotes} mosaicism, where all 15 individuals exhibited a modal chromosome number of 47 (i.e., trisomy 21), and at least two cells lacked one of the three chromosomes 21. The occurrence of aneuploidy for chromosomes 15, 17, and X increased with age, and an inverse correlation between chromosome loss and size was also observed. Because older individuals had not been karyotyped at birth, it was not possible to determine whether our observations were due to either increased survival of mosaic individuals or accumulation of disomy 21 cells via increased chromosome loss with aging of the trisomy 21 individual. Using a modeling approach involving life table methods, we obtained results that suggested acquired mosaicism as the predominant mechanism to explain our findings. These results support the hypothesis that as individuals with DS age, there is an increased loss of chromosome 21. 30 refs., 5 tabs.

  9. Peripherally cross-linking the shell of core-shell polymer micelles decreases premature release of physically loaded combretastatin A4 in whole blood and increases its mean residence time and subsequent potency against primary murine breast tumors after IV administration

    PubMed Central

    Wakaskar, Rajesh R.; Bathena, Sai Praneeth R.; Tallapaka, Shailendra; Ambardekar, Vishakha V.; Gautum, Nagsen; Thakare, Rhishikesh N.; Simet, Samantha M.; Curran, Stephen M.; Singh, Rakesh K.; Dong, Yuxiang

    2014-01-01

    Purpose Determine the feasibility and potential benefit of peripherally cross-linking the shell of core-shell polymer micelles on the premature release of physically loaded hydrophobic drug in whole blood and subsequent potency against solid tumors. Methods Individual Pluronic F127 polymer micelles (F127 PM) peripherally cross-linked with ethylenediamine at 76% of total PEO blocks (X-F127 PM) were physically loaded with combretastatin A4 (CA4) by the solid dispersion method and compared to CA4 physically loaded in uncross-linked F127 PM, CA4 in DMSO in vitro, or water-soluble CA4 phosphate (CA4P) in vivo. Results X-F127 PM had similar CA4 loading and aqueous solubility as F127 PM up to 10 mg CA4 / mL at 22.9 wt% and did not aggregate in PBS or 90% (v/v) human serum at 37°C for at least 24 h. In contrast, X-F127 PM decreased the unbound fraction of CA4 in whole blood (fu) and increased the mean plasma residence time and subsequent potency of CA4 against the vascular function and growth of primary murine 4T1 breast tumors over CA4 in F127 PM and water-soluble CA4P after IV administration. Conclusions Given that decreasing the fu is an indication of decreased drug release, peripherally cross-linking the shell of core-shell polymer micelles may be a simple approach to decrease premature release of physically loaded hydrophobic drug in the blood and increase subsequent potency in solid tumors. PMID:25223962

  10. IL-33 circulating serum levels are increased in patients with non-segmental generalized vitiligo.

    PubMed

    Vaccaro, Mario; Cicero, Francesca; Mannucci, Carmen; Calapai, Gioacchino; Spatari, Giovanna; Barbuzza, Olga; Cannavò, Serafinella P; Gangemi, Sebastiano

    2016-09-01

    IL-33 is a recently identified cytokine, encoded by the IL-33 gene, which is a member of the IL-1 family that drives the production of T-helper-2 (Th-2)-associated cytokines. Serum levels of IL-33 have been reported to be up-regulated in various T-helper (Th)-1/Th-17-mediated diseases, such as psoriasis, rheumatoid arthritis, and inflammatory bowel. To investigate whether cytokine imbalance plays a role in the pathogenesis of vitiligo, we performed a case-control association study by enzyme-linked immunosorbent assay of IL-33 in our patients. IL-33 serum levels were measured by a quantitative enzyme immunoassay technique in patients with non-segmental generalized vitiligo and compared with those of healthy controls. IL-33 serum levels in patients with vitiligo were significantly increased than those in healthy controls. There was a positive correlation of IL-33 serum levels with extension of vitiligo and disease activity. This study suggests a possible systemic role of IL-33 in the pathogenesis of vitiligo. Inhibiting IL-33 activity might be a novel therapeutic strategy in the treatment of autoimmune inflammatory disease, like vitiligo. PMID:27388717

  11. Increase of 210Po levels in human semen fluid after mussel ingestion.

    PubMed

    Kelecom, Alphonse; Gouvea, Rita de Cássia dos Santos

    2011-05-01

    Polonium-210 ((210)Po) radioactive concentrations were determined in human semen fluid of vasectomized non-smoker volunteers. The (210)Po levels ranged from 0.10 to 0.39 mBq g(-1) (mean: 0.23 ± 0.08 mBq g(-1)). This value decreased to 0.10 ± 0.02 mBq g(-1) (range from 0.07 to 0.13 mBq g(-1)) after two weeks of a controlled diet, excluding fish and seafood. Then, volunteers ate during a single meal 200 g of the cooked mussel Perna perna L., and (210)Po levels were determined again, during ten days, in semen fluid samples collected every morning. Volunteers continued with the controlled diet and maintained sexual abstinence through the period of the experiment. A 300% increase of (210)Po level was observed the day following mussel consumption, with a later reduction, such that the level returned to near baseline by day 4.

  12. Increased plasma homocysteine levels in patients with multiple sclerosis and depression

    PubMed Central

    Triantafyllou, Nikolaos; Evangelopoulos, Maria-Eleftheria; Kimiskidis, Vasilios K; Kararizou, Evangelia; Boufidou, Fotini; Fountoulakis, Konstantinos N; Siamouli, Melina; Nikolaou, Chrysoula; Sfagos, Constantinos; Vlaikidis, Nikolaos; Vassilopoulos, Dimitrios

    2008-01-01

    Background The aim of the study was to assess the plasma levels of homocysteine in patients with multiple sclerosis (MS) and to investigate whether an association with depression exists. Methods Plasma homocysteine (Hcy), vitamin B12 and plasma folate were measured in 65 moderately disabled patients with relapsing/remitting MS (RR-MS) and 60 healthy controls. All subjects were assessed with the Beck Depression Inventory (BDI). Results Hcy levels were significantly increased in MS patients compared to controls (13.5 ± 4.7 μmol/l vs 8.5 ± 3.1, p < 0.001). A significant correlation was found between Hcy levels and BDI scores (Pearson r = 0.3025, p < 0.05). Plasma Hcy was not related to Extended Disability Status Scale (EDSS) score, age, disease duration or vitamin B12 and folate. Conclusion Moderately disabled MS patients with elevated Hcy levels are particularly prone to develop depressive symptomatology. Further study is warranted in order to elucidate the prognostic and therapeutic implications of this novel finding. PMID:18782433

  13. Steroid injection for shoulder pain causes prolonged increased glucose level in type 1 diabetics

    PubMed Central

    Povlsen, Bo; Povlsen, Sebastian D

    2014-01-01

    Shoulder pain is very common in diabetic patients and often treated with steroid injections, with subsequent increases in blood glucose levels or the need for additional insulin being questioned. We report a case of significant and prolonged elevation of blood glucose levels and resultant insulin requirement in a type 1 diabetic man after a single 40 mg injection of triamcinolone for shoulder pain. Within 48 h, the shoulder pain as assessed by a visual analogue scale (0–10) was reduced to zero, but the elevated insulin requirements continued for 4 weeks after the injection. This finding suggests that steroid injections for shoulder pain in diabetics may not always be as safe as previously thought. We propose that medical practitioners advise their patients to monitor their glucose levels more carefully after such injections and that caution is exercised when considering administrating these injections to those who have poorly controlled blood glucose levels preinjection to avoid ketoacidosis. PMID:25199186

  14. Increased Gustatory Response Score in Obesity and Association Levels with IL-6 and Leptin

    PubMed Central

    Remla, Nesrine; Hadjidj, Zeyneb; Ghezzaz, Kamel; Moulessehoul, Soraya; Aribi, Mourad

    2016-01-01

    Background. The aim of this study was to investigate the relationship between the circulating IL-6 and leptin levels with taste alteration in young obese patients. Methods. A retrospective case-control study was conducted in thirty obese patients and thirty age- and sex-matched healthy controls. Results. Circulating levels of IL-6 and leptin were significantly increased in obese patients than in controls. However, catalase and ORAC levels were significantly decreased in obese patients compared to controls. Additionally, obese participants had high scores for the detection of fats (gustatory response scores [GRS]; p < 0.001). Moreover, IL-6 and leptin were strongly associated with GRS alteration among patients with GRS 4 (resp., OR =17.5 [95% CI, 1.56–193.32; p = 0.007]; OR = 16 [95% CI, 1.69–151.11; p = 0.006]). For the Mantel-Haenszel common odds ratio estimate (MH OR), IL-6 and leptin were strongly associated with obesity, in patients with either GRS 4 or GRS > 4 (resp., MH OR = 8.77 [95% CI, 2.06–37.44; p = 0.003]; MH OR = 5.76 [95% CI, 1.64–20.24; p = 0.006]). Conclusions. In a low grade inflammation linked to obesity, taste alteration is associated with high levels of IL-6 and leptin. PMID:27413547

  15. Tuning nanoscale viscoelasticity of polyelectrolyte complexes with multiple types of cross-links

    NASA Astrophysics Data System (ADS)

    Ma, Tianzhu; Han, Biao; Lee, Daeyeon; Han, Lin

    Mechanical properties of hydrogels are manifestation of cross-link type and density, fixed charges and water-polymer interactions. In this study, we revealed how different types of cross-links regulate the nanoscale viscoelasticity of polyelectrolyte networks. Ionically cross-linked PAH/PAA layer-by-layer complexes were modified to include covalent cross-links using EDC. AFM-nanoindentation and force relaxation were performed at various ionic strength (0.01-1M) and pH (1.5-5.5). As-assembled networks, held only by ionic cross-links, underwent >95% relaxation, dominated by cross-link breaking and re-formation. Addition of covalent cross-links increased the instantaneous modulus by 1.6-fold and attenuated relaxation to ~80% of net neutral states (pH >=3.5), as covalent cross-links provide additional elastic components. The network remained stabilized when all ionic cross-links were dissociated at pH <=1.5, whereby further attenuation to 31% in relaxation could be due to viscoelastic polymer conformational changes and fluid flow-induced poroelasticity. Taken together, this study demonstrates the potential of using multiple cross-linking types to tune the viscoelastic mechanisms in polyelectrolyte complexes.

  16. Fasting-induced increases in food hoarding are dependent on the foraging-effort level.

    PubMed

    Day, Diane E; Bartness, Timothy J

    2003-04-01

    Two strategies that have evolved to help animals meet energy demands are increases in body fat and in hoarded food. Reliance on each varies, but both are characterized by energy stored in excess of current demands for future use. Fasted Siberian hamsters decrease their lipid stores and, upon refeeding, food hoarding rather than food intake increases. Here, we tested the effect of foraging-effort level on fasting-induced increases in food hoarding and whether decreases in total body fat or individual fat pad masses were associated with the hoarding increases. This was accomplished by housing female Siberian hamsters in a foraging/hoarding system where they earned food pellets upon completion of a programmed number of wheel revolutions (10, 75 or 200 per 75-mg pellet), or had no foraging requirement (free food and an active or blocked running wheel). After baseline, half the hamsters in each group were food deprived for 32 h and then refed (control hamsters were killed after the fast without refeeding). Fasted-refed hamsters increased foraging and food hoarding, especially at the lowest foraging effort, but not food intake, with few exceptions. These responses became progressively smaller as foraging effort increased. Fasting induced similar losses in carcass lipid across foraging efforts, but the lipid loss was not uniform across the fat pads and was not clearly related to hoard size. Collectively, the fasting-induced, increased food hoarding may be triggered by an overall change in energy metabolism rather than by a general or fat-pad-specific decrease in lipid stores. PMID:12782221

  17. Short communication: Effect of increasing levels of corn bran on milk yield and composition.

    PubMed

    Janicek, B N; Kononoff, P J; Gehman, A M; Karges, K; Gibson, M L

    2007-09-01

    Thirty-nine lactating Holstein cows (23 multiparous and 16 primiparous) were randomly assigned to 1 of 3 dietary treatments in a crossover design. Dietary treatments differed by the proportion of corn bran [10, 17.5, and 25% dry matter (DM); designated as low, medium, and high] replacing corn silage and alfalfa. The corn bran coproduct contained 8.2% moisture and 12.9% crude protein, 30.4% neutral detergent fiber (NDF), and 45.0% nonfiber carbohydrate, 9.9% ether extract, and 0.70% P (DM basis). The low treatment consisted of 15.8% NDF from forage (fNDF) and 33.1% total NDF; the medium treatment consisted of 12.9% fNDF and 32.5% total NDF; and the high diet contained 9.9% fNDF and 31.8% total NDF. Dry matter intake was not affected by treatment. The percent milk fat decreased by 0.26% with the inclusion of corn bran from 10 to 25% of the diet DM, but total milk fat yield was not affected. In comparison, corn bran increased yield of milk protein 0.12 kg/d when bran increased from 10 to 25% of the diet DM. Total milk yield tended to increase when bran increased from 10 to 25% of the diet DM, but no differences were observed on 3.5% fat-corrected milk. Lastly, feed conversion significantly improved with increasing inclusion: 1.39, 1.39, and 1.55 +/- 0.05 kg of milk/kg of DMI for low, medium, and high, respectively. Observed effects were likely due to the increase in energy intake associated with increasing levels of corn bran.

  18. Bothrops jararaca Venom Metalloproteinases Are Essential for Coagulopathy and Increase Plasma Tissue Factor Levels during Envenomation

    PubMed Central

    Yamashita, Karine M.; Alves, André F.; Barbaro, Katia C.; Santoro, Marcelo L.

    2014-01-01

    Background/Aims Bleeding tendency, coagulopathy and platelet disorders are recurrent manifestations in snakebites occurring worldwide. We reasoned that by damaging tissues and/or activating cells at the site of the bite and systemically, snake venom toxins might release or decrypt tissue factor (TF), resulting in activation of blood coagulation and aggravation of the bleeding tendency. Thus, we addressed (a) whether TF and protein disulfide isomerase (PDI), an oxireductase involved in TF encryption/decryption, were altered in experimental snake envenomation; (b) the involvement and significance of snake venom metalloproteinases (SVMP) and serine proteinases (SVSP) to hemostatic disturbances. Methods/Principal Findings Crude Bothrops jararaca venom (BjV) was preincubated with Na2-EDTA or AEBSF, which are inhibitors of SVMP and SVSP, respectively, and injected subcutaneously or intravenously into rats to analyze the contribution of local lesion to the development of hemostatic disturbances. Samples of blood, lung and skin were collected and analyzed at 3 and 6 h. Platelet counts were markedly diminished in rats, and neither Na2-EDTA nor AEBSF could effectively abrogate this fall. However, Na2-EDTA markedly reduced plasma fibrinogen consumption and hemorrhage at the site of BjV inoculation. Na2-EDTA also abolished the marked elevation in TF levels in plasma at 3 and 6 h, by both administration routes. Moreover, increased TF activity was also noticed in lung and skin tissue samples at 6 h. However, factor VII levels did not decrease over time. PDI expression in skin was normal at 3 h, and downregulated at 6 h in all groups treated with BjV. Conclusions SVMP induce coagulopathy, hemorrhage and increased TF levels in plasma, but neither SVMP nor SVSP are directly involved in thrombocytopenia. High levels of TF in plasma and TF decryption occur during snake envenomation, like true disseminated intravascular coagulation syndrome, and might be implicated in engendering

  19. High Levels of Heavy Metals Increase the Prevalence of Sarcopenia in the Elderly Population

    PubMed Central

    Yoo, Jun-Il; Lee, Young-Kyun; Koo, Kyung-Hoi

    2016-01-01

    Background Despite increasing concern regarding health problems as a result of environmental pollutants, no association of toxic heavy metals with sarcopenia has been demonstrated in the general population. We investigated the association of heavy metals, including lead, mercury and cadmium, with sarcopenia in the Korean population. Methods Participants included 344 males and 360 females older than 65 years based on data from the fourth and fifth Korea National Health and Nutritional Examination Surveys. Measurements of blood lead, mercury and cadmium levels were performed. To evaluate the cumulative effect of the three heavy metals, subjects were categorized into quartiles. Sarcopenia was defined according to the criteria for the Asia Working Group for Sarcopenia (AWGS) (SMI<5.4 kg/m2 in females and <7.0 kg/m2 in males). Results Of 704 elderly persons (344 in males and 360 in females), prevalences of sarcopenia were 26.7% (92/344) in male and 7.5% (27/360) in female. Mean serum levels of lead in sarcopenia group were significantly higher than non-sarcopenia males (P=0.03). After adjustment for confounding factors, odds ratio for sarcopenia were increased with concentration category of lead (P=0.005 and P<0.001), mercury (P=0.001 and P<0.001) and cadmium (P=0.010 and P<0.001) in males and females, respectively. Conclusions This study demonstrates that high levels of blood lead, mercury and cadmium increase the prevalence of sarcopenia in both genders of elderly populations. PMID:27294082

  20. Tomato juice decreases LDL cholesterol levels and increases LDL resistance to oxidation.

    PubMed

    Silaste, Marja-Leena; Alfthan, Georg; Aro, Antti; Kesäniemi, Y Antero; Hörkkö, Sohvi

    2007-12-01

    High dietary intakes of tomato products are often associated with a reduced risk of CVD, but the atheroprotective mechanisms have not been established. This study was conducted to investigate the effects of increased dietary intake of tomato products on plasma lipids and LDL oxidation. The diet intervention included a baseline period, a 3-week low tomato diet (no tomato products allowed) and a 3-week high tomato diet (400 ml tomato juice and 30 mg tomato ketchup daily). Twenty-one healthy study subjects participated in the study. Total cholesterol concentration was reduced by 5.9 (sd 10) % (P = 0.002) and LDL cholesterol concentration by 12.9 (sd 17.0) % (P = 0.0002) with the high tomato diet compared to the low tomato diet. The changes in total and LDL cholesterol concentrations correlated significantly with the changes in serum lycopene (r 0.56, P = 0.009; r 0.60, P = 0.004, total and LDL, respectively), beta-carotene (r 0.58, P = 0.005; r 0.70, P < 0.001) and gamma-carotene concentrations (r 0.64, P = 0.002; r 0.64, P = 0.002). The level of circulating LDL to resist formation of oxidized phospholipids increased 13 % (P = 0.02) in response to the high tomato diet. In conclusion, a high dietary intake of tomato products had atheroprotective effects, it significantly reduced LDL cholesterol levels, and increased LDL resistance to oxidation in healthy normocholesterolaemic adults. These atheroprotective features associated with changes in serum lycopene, beta-carotene and gamma-carotene levels. PMID:17617941

  1. Increasing levels and biomagnification of persistent organic pollutants (POPs) in Antarctic biota.

    PubMed

    Goerke, Helmut; Weber, Kurt; Bornemann, Horst; Ramdohr, Sven; Plötz, Joachim

    2004-02-01

    Representatives of the Antarctic food web (krill, cephalopod, fish, penguin, seal) of the area around Elephant Island and from the Weddell Sea were analysed for the most recalcitrant organochlorine compounds. Due to sorption of the compounds to sinking particles and accumulation in sediments, two benthic fish species (Gobionotothen gibberifrons, Chaenocephalus aceratus) feeding on benthos invertebrates and fish reflected significantly increasing concentrations within a decade (1987-1996), while a benthopelagic species (Champsocephalus gunnari) feeding on krill did not. In the pelagic food chain, lipid normalised concentrations of all compounds increased from Antarctic krill to fish proving that biomagnification of highly lipophilic pollutants (log octanol-water partition coefficient>5) occurs in water-breathing animals. As top predators Weddell and southern elephant seals (Leptonychotes weddellii, Mirounga leonina) biomagnified the persistent organic pollutants relative to krill 30-160 fold with the exception of hexachlorobenzene, the levels of which were lower than in fish indicating its intense specific elimination.

  2. Organohalogen levels in harbor seal (Phoca vitulina) pups increase with duration of nursing.

    PubMed

    Neale, Jennifer C C; Schmelzer, Kara R; Gulland, Frances M D; Berg, Elizabeth A; Tjeerdema, Ronald S

    2005-05-14

    Maternal transfer of persistent marine contaminants to offspring via milk has been documented in marine mammals, but temporal dynamics of this phenomenon throughout the lactation period are poorly understood. Exposures to organohalogens were investigated in harbor seal pups admitted to a rehabilitation center in north central California during the lactation periods of 2001 and 2002. Ten congeners of PCBs, three congeners of PBDEs, and p,p'-DDE were quantified in whole blood samples. Levels of contaminants increased with admit date, assumed to correlate positively with pup age. This trend was significant when latitude of stranding site, body condition, and body length were included as variables in the model. Contaminant-admit date relationships appeared nonlinear (i.e., threshold or exponential), with greatest increases in contaminant concentrations during late lactation. PMID:16020196

  3. In vivo levels of mitochondrial hydrogen peroxide increase with age in mtDNA mutator mice.

    PubMed

    Logan, Angela; Shabalina, Irina G; Prime, Tracy A; Rogatti, Sebastian; Kalinovich, Anastasia V; Hartley, Richard C; Budd, Ralph C; Cannon, Barbara; Murphy, Michael P

    2014-08-01

    In mtDNA mutator mice, mtDNA mutations accumulate leading to a rapidly aging phenotype. However, there is little evidence of oxidative damage to tissues, and when analyzed ex vivo, no change in production of the reactive oxygen species (ROS) superoxide and hydrogen peroxide by mitochondria has been reported, undermining the mitochondrial oxidative damage theory of aging. Paradoxically, interventions that decrease mitochondrial ROS levels in vivo delay onset of aging. To reconcile these findings, we used the mitochondria-targeted mass spectrometry probe MitoB to measure hydrogen peroxide within mitochondria of living mice. Mitochondrial hydrogen peroxide was the same in young mutator and control mice, but as the mutator mice aged, hydrogen peroxide increased. This suggests that the prolonged presence of mtDNA mutations in vivo increases hydrogen peroxide that contributes to an accelerated aging phenotype, perhaps through the activation of pro-apoptotic and pro-inflammatory redox signaling pathways.

  4. Energized by love: thinking about romantic relationships increases positive affect and blood glucose levels.

    PubMed

    Stanton, Sarah C E; Campbell, Lorne; Loving, Timothy J

    2014-10-01

    We assessed the impact of thinking of a current romantic partner on acute blood glucose responses and positive affect over a short period of time. Participants in romantic relationships were randomly assigned to reflect on their partner, an opposite-sex friend, or their morning routine. Blood glucose levels were assessed prior to reflection, as well as at 10 and 25 min postreflection. Results revealed that individuals in the routine and friend conditions exhibited a decline in glucose over time, whereas individuals in the partner condition did not exhibit this decline (rather, a slight increase) in glucose over time. Reported positive affect following reflection was positively associated with increases in glucose, but only for individuals who reflected on their partner, suggesting this physiological response reflects eustress. These findings add to the literature on eustress in relationships and have implications for relationship processes.

  5. Serum Prosaposin Levels Are Increased in Patients with Advanced Prostate Cancer

    PubMed Central

    Koochekpour, Shahriar; Hu, Siyi; Vellasco-Gonzalez, Cruz; Bernardo, Ruiz; Azabdaftari, Gissue; Dalin, Guo-xiang; Zhau, Haiyen E.; Chung, Leland W.; Vessella, Robert L.

    2012-01-01

    BACKGROUND We previously cloned prosaposin (PSAP) from metastatic castrate-resistant prostate cancer (mCRPCa) cells and demonstrated its genomic amplification and/or overexpression in metastatic PCa cell lines, xenografts, and lymph node metastases. The clinicohistopathological significance of serum-PSAP levels and its tissue expression and association with predictive or prognostic variable in primary or advanced PCa are not known. METHODS We examined PSAP expression by immunohistochemical staining during early embryogenic development of the prostate and within a large tissue microarray which included 266 benign and malignant prostate tissues. In addition, serum PSAP levels in the age-adjusted normal male population and in 154 normal individuals and patients with primary or mCRPCa were measured by an ELISA assay. RESULTS Univariate and multivariate analyses revealed a significant and inverse association between PSAP expression and clinical stage II and III tumors, dominant Gleason patterns 3 and 4, and seminal vesicle invasion. In the normal male population, the lowest serum-PSAP level was detected before puberty, peaked at the most reproductive age group (20–39 years old), and then, decreased to a range between the two groups for men above 40 years old. Regardless of age and when compared with normal individuals, serum-PSAP levels significantly decreased in primary organ-confined PCa, but increased in those with mCRPCa. CONCLUSION Our results show that PSAP has the potential to differentiate between primary and advanced PCa. Additional large-scale studies are needed to define the usefulness of tissue expression or serum-PSAP levels as a diagnostic or prognostic marker or as a therapeutic target in PCa. PMID:21630292

  6. Chronic mild stress increases alcohol intake in mice with low dopamine D2 receptor levels.

    PubMed

    Delis, Foteini; Thanos, Panayotis K; Rombola, Christina; Rosko, Lauren; Grandy, David; Wang, Gene-Jack; Volkow, Nora D

    2013-02-01

    Alcohol use disorders emerge from a complex interaction between environmental and genetic factors. Stress and dopamine D2 receptor levels (DRD2) have been shown to play a central role in alcoholism. To better understand the interactions between DRD2 and stress in ethanol intake behavior, we subjected Drd2 wild-type (+/+), heterozygous (+/-), and knockout (-/-) mice to 4 weeks of chronic mild stress (CMS) and to an ethanol two-bottle choice during CMS weeks 2-4. Prior to and at the end of the experiment, the animals were tested in the forced swim and open field tests. We measured ethanol intake and preference, immobility in the force swim test, and activity in the open field. We show that under no CMS, Drd2+/- and Drd2-/- mice had lower ethanol intake and preference compared with Drd2+/+. Exposure to CMS decreased ethanol intake and preference in Drd2+/+ and increased them in Drd2+/- and Drd2-/- mice. At baseline, Drd2+/- and Drd2-/- mice had significantly lower activity in the open field than Drd2+/+, whereas no genotype differences were observed in the forced swim test. Exposure to CMS increased immobility during the forced swim test in Drd2+/- mice, but not in Drd2+/+ or Drd2-/- mice, and ethanol intake reversed this behavior. No changes were observed in open field test measures. These findings suggest that in the presence of a stressful environment, low DRD2 levels are associated with increased ethanol intake and preference and that under this condition, increased ethanol consumption could be used as a strategy to alleviate negative mood. PMID:23148856

  7. Protein folding: Turbo-charged crosslinking

    NASA Astrophysics Data System (ADS)

    Craik, David J.

    2012-08-01

    The efficient production of stable bioactive proteins often requires the selective formation of several disulfide crosslinks. Two recent studies have now shown that replacing cysteine with selenocysteine in the unfolded protein can autocatalyse the formation of the desired crosslinks.

  8. Future Climate CO2 Levels Mitigate Stress Impact on Plants: Increased Defense or Decreased Challenge?

    PubMed Central

    AbdElgawad, Hamada; Zinta, Gaurav; Beemster, Gerrit T. S.; Janssens, Ivan A.; Asard, Han

    2016-01-01

    Elevated atmospheric CO2 can stimulate plant growth by providing additional C (fertilization effect), and is observed to mitigate abiotic stress impact. Although, the mechanisms underlying the stress mitigating effect are not yet clear, increased antioxidant defenses, have been held primarily responsible (antioxidant hypothesis). A systematic literature analysis, including “all” papers [Web of Science (WoS)-cited], addressing elevated CO2 effects on abiotic stress responses and antioxidants (105 papers), confirms the frequent occurrence of the stress mitigation effect. However, it also demonstrates that, in stress conditions, elevated CO2 is reported to increase antioxidants, only in about 22% of the observations (e.g., for polyphenols, peroxidases, superoxide dismutase, monodehydroascorbate reductase). In most observations, under stress and elevated CO2 the levels of key antioxidants and antioxidant enzymes are reported to remain unchanged (50%, e.g., ascorbate peroxidase, catalase, ascorbate), or even decreased (28%, e.g., glutathione peroxidase). Moreover, increases in antioxidants are not specific for a species group, growth facility, or stress type. It seems therefore unlikely that increased antioxidant defense is the major mechanism underlying CO2-mediated stress impact mitigation. Alternative processes, probably decreasing the oxidative challenge by reducing ROS production (e.g., photorespiration), are therefore likely to play important roles in elevated CO2 (relaxation hypothesis). Such parameters are however rarely investigated in connection with abiotic stress relief. Understanding the effect of elevated CO2 on plant growth and stress responses is imperative to understand the impact of climate changes on plant productivity. PMID:27200030

  9. Future Climate CO2 Levels Mitigate Stress Impact on Plants: Increased Defense or Decreased Challenge?

    PubMed

    AbdElgawad, Hamada; Zinta, Gaurav; Beemster, Gerrit T S; Janssens, Ivan A; Asard, Han

    2016-01-01

    Elevated atmospheric CO2 can stimulate plant growth by providing additional C (fertilization effect), and is observed to mitigate abiotic stress impact. Although, the mechanisms underlying the stress mitigating effect are not yet clear, increased antioxidant defenses, have been held primarily responsible (antioxidant hypothesis). A systematic literature analysis, including "all" papers [Web of Science (WoS)-cited], addressing elevated CO2 effects on abiotic stress responses and antioxidants (105 papers), confirms the frequent occurrence of the stress mitigation effect. However, it also demonstrates that, in stress conditions, elevated CO2 is reported to increase antioxidants, only in about 22% of the observations (e.g., for polyphenols, peroxidases, superoxide dismutase, monodehydroascorbate reductase). In most observations, under stress and elevated CO2 the levels of key antioxidants and antioxidant enzymes are reported to remain unchanged (50%, e.g., ascorbate peroxidase, catalase, ascorbate), or even decreased (28%, e.g., glutathione peroxidase). Moreover, increases in antioxidants are not specific for a species group, growth facility, or stress type. It seems therefore unlikely that increased antioxidant defense is the major mechanism underlying CO2-mediated stress impact mitigation. Alternative processes, probably decreasing the oxidative challenge by reducing ROS production (e.g., photorespiration), are therefore likely to play important roles in elevated CO2 (relaxation hypothesis). Such parameters are however rarely investigated in connection with abiotic stress relief. Understanding the effect of elevated CO2 on plant growth and stress responses is imperative to understand the impact of climate changes on plant productivity.

  10. Textural performance of crosslinked or reduced-calcium milk protein ingredients in model high-protein nutrition bars.

    PubMed

    Banach, J C; Clark, S; Metzger, L E; Lamsal, B P

    2016-08-01

    Transglutaminase (Tgase) crosslinking and calcium reduction were investigated as ways to improve the texture and storage stability of high-protein nutrition (HPN) bars formulated with milk protein concentrate (MPC) and micellar casein concentrate (MCC). The MPC and MCC crosslinked at none, low, and high levels, and a reduced-calcium MPC (RCMPC) were each formulated into model HPN bars. Hardness, crumbliness, moisture content, pH, color, and water activity of the HPN bars were measured during accelerated storage. The HPN bars prepared with MPC were harder and more cohesive than those prepared with MCC. Higher levels of Tgase crosslinking improved HPN bar cohesiveness and decreased hardening during storage. The RCMPC produced softer, yet crumblier HPN bars. Small textural differences were observed for the HPN bars formulated with the transglutaminase crosslinked proteins or RCMPC when compared with their respective controls. However, modification only slightly improved protein ingredient ability to slow hardening while balancing cohesion and likely requires further improvement for increased applicability in soft-texture HPN bars. PMID:27236767

  11. Textural performance of crosslinked or reduced-calcium milk protein ingredients in model high-protein nutrition bars.

    PubMed

    Banach, J C; Clark, S; Metzger, L E; Lamsal, B P

    2016-08-01

    Transglutaminase (Tgase) crosslinking and calcium reduction were investigated as ways to improve the texture and storage stability of high-protein nutrition (HPN) bars formulated with milk protein concentrate (MPC) and micellar casein concentrate (MCC). The MPC and MCC crosslinked at none, low, and high levels, and a reduced-calcium MPC (RCMPC) were each formulated into model HPN bars. Hardness, crumbliness, moisture content, pH, color, and water activity of the HPN bars were measured during accelerated storage. The HPN bars prepared with MPC were harder and more cohesive than those prepared with MCC. Higher levels of Tgase crosslinking improved HPN bar cohesiveness and decreased hardening during storage. The RCMPC produced softer, yet crumblier HPN bars. Small textural differences were observed for the HPN bars formulated with the transglutaminase crosslinked proteins or RCMPC when compared with their respective controls. However, modification only slightly improved protein ingredient ability to slow hardening while balancing cohesion and likely requires further improvement for increased applicability in soft-texture HPN bars.

  12. Novel antimicrobial superporous cross-linked chitosan/pyromellitimide benzoyl thiourea hydrogels.

    PubMed

    Mohamed, Nadia A; Abd El-Ghany, Nahed A; Fahmy, Mona M

    2016-01-01

    In this work, chitosan (CS) was cross-linked with different amounts of pyromellitimide benzoyl thiourea moieties. The structure of the cross-linked CS was confirmed by elemental analyses, FTIR and (1)H- NMR spectroscopy. The cross-linking process proceeds via reacting of the amino groups of CS with the isothiocyanate groups of the N,N'-bis [4-(isothiocyanate carbonyl)phenyl] pyromellitimide cross-linker. The amount of the cross-linker was varied with respect to CS to produce four new pyromellitimide benzoyl thiourea cross-linked CS (PIBTU-CS) hydrogels designated as PIBTU-CS-1, PIBTU-CS-2, PIBTU-CS-3, and PIBTU-CS-4 of increasing cross-linking degree percent of 11, 22, 44 and 88%, respectively. The scanning electron microscopy observation indicates the extremely porous structure of the hydrogels. XRD results showed that the crystallinity of CS was decreased upon cross-linking. The four hydrogels exhibit a higher antibacterial activity on Bacillus subtilis and Streptococcus pneumoniae as Gram positive bacteria and against Escherichia coli as Gram negative bacteria and higher antifungal activity on Aspergillus fumigatus, Syncephalastrum racemosum and Geotricum candidum than that of the parent CS as shown from their higher inhibition zone diameters and their lower MIC values. The swell ability of the hydrogel as well as their antimicrobial activity increased with increasing cross-linking density. PMID:26388182

  13. Novel antimicrobial superporous cross-linked chitosan/pyromellitimide benzoyl thiourea hydrogels.

    PubMed

    Mohamed, Nadia A; Abd El-Ghany, Nahed A; Fahmy, Mona M

    2016-01-01

    In this work, chitosan (CS) was cross-linked with different amounts of pyromellitimide benzoyl thiourea moieties. The structure of the cross-linked CS was confirmed by elemental analyses, FTIR and (1)H- NMR spectroscopy. The cross-linking process proceeds via reacting of the amino groups of CS with the isothiocyanate groups of the N,N'-bis [4-(isothiocyanate carbonyl)phenyl] pyromellitimide cross-linker. The amount of the cross-linker was varied with respect to CS to produce four new pyromellitimide benzoyl thiourea cross-linked CS (PIBTU-CS) hydrogels designated as PIBTU-CS-1, PIBTU-CS-2, PIBTU-CS-3, and PIBTU-CS-4 of increasing cross-linking degree percent of 11, 22, 44 and 88%, respectively. The scanning electron microscopy observation indicates the extremely porous structure of the hydrogels. XRD results showed that the crystallinity of CS was decreased upon cross-linking. The four hydrogels exhibit a higher antibacterial activity on Bacillus subtilis and Streptococcus pneumoniae as Gram positive bacteria and against Escherichia coli as Gram negative bacteria and higher antifungal activity on Aspergillus fumigatus, Syncephalastrum racemosum and Geotricum candidum than that of the parent CS as shown from their higher inhibition zone diameters and their lower MIC values. The swell ability of the hydrogel as well as their antimicrobial activity increased with increasing cross-linking density.

  14. Increased interleukin 1 and tumor necrosis factor alpha levels after thyroid surgery

    PubMed Central

    Özçınar, Beyza; Aksakal, Nihat; Yanar, Fatih; Ağcaoğlu, Orhan; Peker, Kıvanç Derya; Türkoğlu, Ümit; Mercan, Selçuk; Özarmağan, Selçuk; Erbil, Yeşim

    2014-01-01

    Objective: The aim of this study was to consider levels of the proinflammatory cytokines IL-1 and TNFα after thyroid surgery. Material and Methods: A total of 200 patients who underwent total thyroidectomy enrolled in this study. Drain fluid samples were taken. IL-1 and TNFα results and their relationship with other factors were analyzed. Results: There was a positive correlation between IL-1 and hyperthyroidism (rs=0.614, p<0.001), operative time (rs=0.770, p<0.001), and excised thyroid volume (rs=0.829, p<0.001). Moreover, there was a positive correlation between TNFα and hyperthyroidism (rs=0.430, p<0.001), operative time (rs=0.392, p<0.001), and excised thyroid volume (rs=0.398, p<0.001). Conclusion: The results of this study showed us that the parameters related to increased proinflammatory cytokine levels after thyroid surgery were hyperthyroidism, operative time, and excised thyroid volume, but this increase did not show us any clinical outcomes related to these parameters. PMID:25931900

  15. Income inequality and schizophrenia: Increased schizophrenia incidence in countries with high levels of income inequality

    PubMed Central

    Burns, Jonathan K.; Tomita, Andrew; Kapadia, Amy S.

    2014-01-01

    Background Income inequality is associated with numerous negative health outcomes. There is evidence that ecological level socio-environmental factors may increase risk for schizophrenia. Aims The aim was to investigate whether measures of income inequality are associated with incidence of schizophrenia at the country level. Method We conducted a systematic review of incidence rates for schizophrenia, reported between 1975 and 2011. For each country, national measures of income inequality (Gini coefficient) along with covariate risk factors for schizophrenia were obtained. Multilevel mixed-effects Poisson regression was performed to investigate the relationship between Gini coefficients and incidence rates of schizophrenia controlling for covariates. Results One hundred and seven incidence rates (from 26 countries) were included. Mean incidence of schizophrenia was 18.50 per 100,000 (SD 11.9; range=1.7-67). There was a significant positive relationship between incidence rate of schizophrenia and Gini coefficient (β = 1.02; Z = 2.28; p = 0.02; 95% CI 1.00, 1.03). Conclusions Countries characterized by a large rich-poor gap may be at increased risk of schizophrenia. We suggest that income inequality impacts negatively on social cohesion, eroding social capital; and that chronic stress associated with living in highly disparate societies places individuals at risk of schizophrenia. PMID:23594564

  16. Targeting increased copper levels in diethylnitrosamine induced hepatocellular carcinoma cells in rats by epigallocatechin-3-gallate.

    PubMed

    Farhan, Mohd; Rizvi, Asim; Naseem, Imrana; Hadi, S M; Ahmad, Aamir

    2015-11-01

    We have earlier elucidated a pathway for the anticancer action of plant polyphenolic compounds against malignant cells involving mobilisation of endogenous copper ions and the consequent prooxidant action. To further confirm our hypothesis in vivo, we induced hepatocellular carcinoma (HCC) in rats by diethylnitrosamine (DEN). We show that in such carcinoma cells, there is a progressive elevation in copper levels at various intervals after DEN administration. Concurrently with increasing copper levels, epigallocatechin-3-gallate (EGCG; a potent anticancer plant polyphenol found in green tea) mediated DNA breakage in malignant cells is also increased. The cell membrane permeable copper chelator neocuproine inhibited the EGCG-mediated cellular DNA degradation, whereas the membrane impermeable chelator bathocuproine was ineffective. Iron and zinc specific chelators desferoxamine mesylate and histidine, respectively, were also ineffective in inhibiting EGCG mediated DNA breakage. Through the use of specific scavengers, the mechanism of DNA breakage was determined to be mediated by reactive oxygen species. In summary, we provide an in vivo evidence of accumulating copper in hepatocellular carcinoma that is targeted by EGCG, leading to its anticancer role in a prooxidant manner. Our findings confirm a novel mechanism of anticancer activity of EGCG in particular and plant derived nutraceuticals in general.

  17. Excitotoxic and Radiation Stress Increase TERT Levels in the Mitochondria and Cytosol of Cerebellar Purkinje Neurons.

    PubMed

    Eitan, Erez; Braverman, Carmel; Tichon, Ailone; Gitler, Daniel; Hutchison, Emmette R; Mattson, Mark P; Priel, Esther

    2016-08-01

    Telomerase reverse transcriptase (TERT) is the catalytic subunit of telomerase, an enzyme that elongates telomeres at the ends of chromosomes during DNA replication. Recently, it was shown that TERT has additional roles in cell survival, mitochondrial function, DNA repair, and Wnt signaling, all of which are unrelated to telomeres. Here, we demonstrate that TERT is enriched in Purkinje neurons, but not in the granule cells of the adult mouse cerebellum. TERT immunoreactivity in Purkinje neurons is present in the nucleus, mitochondria, and cytoplasm. Furthermore, TERT co-localizes with mitochondrial markers, and immunoblot analysis of protein extracts from isolated mitochondria and synaptosomes confirmed TERT localization in mitochondria. TERT expression in Purkinje neurons increased significantly in response to two stressors: a sub-lethal dose of X-ray radiation and exposure to a high glutamate concentration. While X-ray radiation increased TERT levels in the nucleus, glutamate exposure elevated TERT levels in mitochondria. Our findings suggest that in mature Purkinje neurons, TERT is present both in the nucleus and in mitochondria, where it may participate in adaptive responses of the neurons to excitotoxic and radiation stress. PMID:26374457

  18. Syringe Exchange in the United States: A National Level Economic Evaluation of Hypothetical Increases in Investment

    PubMed Central

    Weir, Brian W.; Des Jarlais, Don C.; Pinkerton, Steven D.; Holtgrave, David R.

    2014-01-01

    To examine whether increasing investment in needle/syringe exchange programs (NSPs) in the US would be cost-effective for HIV prevention, we modeled HIV incidence in hypothetical cases with higher NSP syringe supply than current levels, and estimated number of infections averted, cost per infection averted, treatment costs saved, and financial return on investment. We modified Pinkerton’s model, which was an adaptation of Kaplan’s simplified needle circulation theory model, to compare different syringe supply levels, account for syringes from non-NSP sources, and reflect reduction in syringe sharing and contamination. With an annual $10 to $50 million funding increase, 194–816 HIV infections would be averted (cost per infection averted $51,601– $61,302). Contrasted with HIV treatment cost savings alone, the rate of financial return on investment would be 7.58–6.38. Main and sensitivity analyses strongly suggest that it would be cost-saving for the US to invest in syringe exchange expansion. PMID:24824043

  19. Increased plasma levels of CK-18 as potential cell death biomarker in patients with HELLP syndrome

    PubMed Central

    John, K; Wielgosz, S; Schulze-Osthoff, K; Bantel, H; Hass, R

    2013-01-01

    HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome represents a life-threatening pregnancy disorder with high fetal and maternal mortality, but its underlying molecular mechanisms remain unknown. Although apoptosis has been implicated in HELLP syndrome, its pathogenic role remains largely unclear. In the present study, we investigated whether the detection of apoptosis by novel plasma biomarkers is of diagnostic value in HELLP patients. For this purpose, we analyzed two biomarkers that specifically detect apoptosis or overall cell death of epithelial cells, such as hepatocytes or placental trophoblasts, through the release of caspase-cleaved or total (caspase-cleaved and uncleaved) cytokeratin-18 (CK-18) in plasma of HELLP patients compared with pregnant as well as non-pregnant healthy women. In addition, caspase activation and cell death were determined in placental tissues of HELLP patients and individuals with normal pregnancy. In contrast to pregnant or non-pregnant healthy controls, we observed significantly increased levels of both caspase-cleaved and total CK-18 in plasma of HELLP patients. Following delivery, CK-18 levels rapidly decreased in HELLP patients. Caspase activation and cell death were also elevated in placental tissues from HELLP patients compared with healthy pregnant women. These data demonstrate not only that apoptosis is increased in HELLP syndrome, but also that caspase-cleaved or total CK-18 are promising plasma biomarkers to identify patients with HELLP syndrome. Thus, further studies are warranted to evaluate the utility of these biomarkers for monitoring disease activity in HELLP syndrome. PMID:24157880

  20. Direct Pore-Level Observation of Permeability Increase by Seismic Waves

    NASA Astrophysics Data System (ADS)

    Beresnev, I. A.; Gaul, W.; Vigil, D.

    2011-12-01

    Increases in permeability of natural reservoirs and aquifers by passing seismic waves have been well documented. If the physical causes of this phenomenon can be understood, technological applications would be possible for controlling the flow in hydrologic systems or enhancing production from oil reservoirs. The explanation of the dynamically increased mobility of underground fluids lies at the pore level. The natural fluids can be viewed as two-phase systems, composed of water as the wetting phase and of dispersed non-wetting globules of gas or organic fluids flowing through tortuous constricted channels. Capillary forces prevent the free motion of the suspended non-wetting droplets, which tend to become immobilized in capillary constrictions. The capillary entrapment significantly reduces macroscopic permeability. In a controlled experiment with a constricted capillary channel, we immobilize the suspended ganglia and test the model of capillary entrapment: it agrees precisely with the experiment. We then demonstrate by direct optical pore-level observation that the vibrations applied to the wall of the channel liberate the trapped ganglia if a certain critical acceleration is reached. When the droplet begins to progressively advance, the permeability is restored. The mobilizing acceleration in the elastic wave, needed to "unplug" an immobile flow, is theoretically predicted within a factor of 1-5 of the experimental value. Overcoming the capillary entrapment in porous channels is hypothesized to be one of the principal mechanisms by which natural permeabilities are enhanced by the passage of seismic waves.

  1. Direct pore-level observation of permeability increase in two-phase flow by shaking

    NASA Astrophysics Data System (ADS)

    Beresnev, Igor; Gaul, William; Vigil, R. Dennis

    2011-10-01

    Increases in permeability of natural reservoirs and aquifers by passing seismic waves have been well documented. If the physical causes of this phenomenon can be understood, technological applications would be possible for controlling the flow in hydrologic systems or enhancing production from oil reservoirs. The explanation of the dynamically increased mobility of underground fluids must lie at the pore level. The natural fluids can be viewed as two-phase systems, composed of water as the wetting phase and of dispersed non-wetting globules of gas or organic fluids, flowing through tortuous constricted channels. Capillary forces prevent free motion of the suspended non-wetting droplets, which tend to become immobilized in capillary constrictions. The capillary entrapment significantly reduces macroscopic permeability. In a controlled experiment with a constricted capillary channel, we immobilize the suspended ganglia and test the model of capillary entrapment: it agrees precisely with the experiment. We then demonstrate by direct optical pore-level observation that the vibrations applied to the wall of the channel liberate the trapped ganglia if a predictable critical acceleration is reached. When the droplet begins to progressively advance, the permeability is restored. The mobilizing acceleration in the elastic wave, needed to “unplug” an immobile flow, is theoretically calculated within a factor of 1-5 of the experimental value. Overcoming the capillary entrapment in porous channels is hypothesized to be one of the principal pore-scale mechanisms by which natural permeabilities are enhanced by the passage of elastic waves.

  2. Increased glucose metabolism and ATP level in brain tissue of Huntington's disease transgenic mice.

    PubMed

    Oláh, Judit; Klivényi, Péter; Gardián, Gabriella; Vécsei, László; Orosz, Ferenc; Kovacs, Gabor G; Westerhoff, Hans V; Ovádi, Judit

    2008-10-01

    Huntington's disease (HD) is a progressive neurodegenerative disorder characterized by multifarious dysfunctional alterations including mitochondrial impairment. In the present study, the formation of inclusions caused by the mutation of huntingtin protein and its relationship with changes in energy metabolism and with pathological alterations were investigated both in transgenic and 3-nitropropionic acid-treated mouse models for HD. The HD and normal mice were characterized clinically; the affected brain regions were identified by immunohistochemistry and used for biochemical analysis of the ATP-producing systems in the cytosolic and the mitochondrial compartments. In both HD models, the activities of some glycolytic enzymes were somewhat higher. By contrast, the activity of glyceraldehyde-3-phosphate dehydrogenase was much lower in the affected region of the brain compared to that of the control. Paradoxically, at the system level, glucose conversion into lactate was enhanced in cytosolic extracts from the HD brain tissue, and the level of ATP was higher in the tissue itself. The paradox could be resolved by taking all the observed changes in glycolytic enzymes into account, ensuing an experiment-based detailed mathematical model of the glycolytic pathway. The mathematical modelling using the experimentally determined kinetic parameters of the individual enzymes and the well-established rate equations predicted the measured flux and concentrations in the case of the control. The same mathematical model with the experimentally determined altered V(max) values of the enzymes did account for an increase of glycolytic flux in the HD sample, although the extent of the increase was not predicted quantitatively. This suggested a somewhat altered regulation of this major metabolic pathway in HD tissue. We then used the mathematical model to develop a hypothesis for a new regulatory interaction that might account for the observed changes; in HD, glyceraldehyde-3-phosphate

  3. Stabilization of collagen nanofibers with L-lysine improves the ability of carbodiimide cross-linked amniotic membranes to preserve limbal epithelial progenitor cells.

    PubMed

    Lai, Jui-Yang; Wang, Pei-Ran; Luo, Li-Jyuan; Chen, Si-Tan

    2014-01-01

    To overcome the drawbacks associated with limited cross-linking efficiency of carbodiimide modified amniotic membrane, this study investigated the use of L-lysine as an additional amino acid bridge to enhance the stability of a nanofibrous tissue matrix for a limbal epithelial cell culture platform. Results of ninhydrin assays and zeta potential measurements showed that the amount of positively charged amino acid residues incorporated into the tissue collagen chains is highly correlated with the L-lysine-pretreated concentration. The cross-linked structure and hydrophilicity of amniotic membrane scaffolding materials affected by the lysine molecular bridging effects were determined. With an increase in the L-lysine-pretreated concentration from 1 to 30 mM, the cross-linking density was significantly increased and water content was markedly decreased. The variations in resistance to thermal denaturation and enzymatic degradation were in accordance with the number of cross-links per unit mass of amniotic membrane, indicating L-lysine-modulated stabilization of collagen molecules. It was also noteworthy that the carbodiimide cross-linked tissue samples prepared using a relatively high L-lysine-pretreated concentration (ie, 30 mM) appeared to have decreased light transmittance and biocompatibility, probably due to the influence of a large nanofiber size and a high charge density. The rise in stemness gene and protein expression levels was dependent on improved cross-link formation, suggesting the crucial role of amino acid bridges in constructing suitable scaffolds to preserve limbal progenitor cells. It is concluded that mild to moderate pretreatment conditions (ie, 3-10 mM L-lysine) can provide a useful strategy to assist in the development of carbodiimide cross-linked amniotic membrane as a stable stem cell niche for corneal epithelial tissue engineering. PMID:25395849

  4. Stabilization of collagen nanofibers with L-lysine improves the ability of carbodiimide cross-linked amniotic membranes to preserve limbal epithelial progenitor cells.

    PubMed

    Lai, Jui-Yang; Wang, Pei-Ran; Luo, Li-Jyuan; Chen, Si-Tan

    2014-01-01

    To overcome the drawbacks associated with limited cross-linking efficiency of carbodiimide modified amniotic membrane, this study investigated the use of L-lysine as an additional amino acid bridge to enhance the stability of a nanofibrous tissue matrix for a limbal epithelial cell culture platform. Results of ninhydrin assays and zeta potential measurements showed that the amount of positively charged amino acid residues incorporated into the tissue collagen chains is highly correlated with the L-lysine-pretreated concentration. The cross-linked structure and hydrophilicity of amniotic membrane scaffolding materials affected by the lysine molecular bridging effects were determined. With an increase in the L-lysine-pretreated concentration from 1 to 30 mM, the cross-linking density was significantly increased and water content was markedly decreased. The variations in resistance to thermal denaturation and enzymatic degradation were in accordance with the number of cross-links per unit mass of amniotic membrane, indicating L-lysine-modulated stabilization of collagen molecules. It was also noteworthy that the carbodiimide cross-linked tissue samples prepared using a relatively high L-lysine-pretreated concentration (ie, 30 mM) appeared to have decreased light transmittance and biocompatibility, probably due to the influence of a large nanofiber size and a high charge density. The rise in stemness gene and protein expression levels was dependent on improved cross-link formation, suggesting the crucial role of amino acid bridges in constructing suitable scaffolds to preserve limbal progenitor cells. It is concluded that mild to moderate pretreatment conditions (ie, 3-10 mM L-lysine) can provide a useful strategy to assist in the development of carbodiimide cross-linked amniotic membrane as a stable stem cell niche for corneal epithelial tissue engineering.

  5. Stabilization of collagen nanofibers with l-lysine improves the ability of carbodiimide cross-linked amniotic membranes to preserve limbal epithelial progenitor cells

    PubMed Central

    Lai, Jui-Yang; Wang, Pei-Ran; Luo, Li-Jyuan; Chen, Si-Tan

    2014-01-01

    To overcome the drawbacks associated with limited cross-linking efficiency of carbodiimide modified amniotic membrane, this study investigated the use of l-lysine as an additional amino acid bridge to enhance the stability of a nanofibrous tissue matrix for a limbal epithelial cell culture platform. Results of ninhydrin assays and zeta potential measurements showed that the amount of positively charged amino acid residues incorporated into the tissue collagen chains is highly correlated with the l-lysine-pretreated concentration. The cross-linked structure and hydrophilicity of amniotic membrane scaffolding materials affected by the lysine molecular bridging effects were determined. With an increase in the l-lysine-pretreated concentration from 1 to 30 mM, the cross-linking density was significantly increased and water content was markedly decreased. The variations in resistance to thermal denaturation and enzymatic degradation were in accordance with the number of cross-links per unit mass of amniotic membrane, indicating l-lysine-modulated stabilization of collagen molecules. It was also noteworthy that the carbodiimide cross-linked tissue samples prepared using a relatively high l-lysine-pretreated concentration (ie, 30 mM) appeared to have decreased light transmittance and biocompatibility, probably due to the influence of a large nanofiber size and a high charge density. The rise in stemness gene and protein expression levels was dependent on improved cross-link formation, suggesting the crucial role of amino acid bridges in constructing suitable scaffolds to preserve limbal progenitor cells. It is concluded that mild to moderate pretreatment conditions (ie, 3–10 mM l-lysine) can provide a useful strategy to assist in the development of carbodiimide cross-linked amniotic membrane as a stable stem cell niche for corneal epithelial tissue engineering. PMID:25395849

  6. Modeling effectiveness of gradual increases in source level to mitigate effects of sonar on marine mammals.

    PubMed

    Von Benda-Beckmann, Alexander M; Wensveen, Paul J; Kvadsheim, Petter H; Lam, Frans-Peter A; Miller, Patrick J O; Tyack, Peter L; Ainslie, Michael A

    2014-02-01

    Ramp-up or soft-start procedures (i.e., gradual increase in the source level) are used to mitigate the effect of sonar sound on marine mammals, although no one to date has tested whether ramp-up procedures are effective at reducing the effect of sound on marine mammals. We investigated the effectiveness of ramp-up procedures in reducing the area within which changes in hearing thresholds can occur. We modeled the level of sound killer whales (Orcinus orca) were exposed to from a generic sonar operation preceded by different ramp-up schemes. In our model, ramp-up procedures reduced the risk of killer whales receiving sounds of sufficient intensity to affect their hearing. The effectiveness of the ramp-up procedure depended strongly on the assumed response threshold and differed with ramp-up duration, although extending the duration of the ramp up beyond 5 min did not add much to its predicted mitigating effect. The main factors that limited effectiveness of ramp up in a typical antisubmarine warfare scenario were high source level, rapid moving sonar source, and long silences between consecutive sonar transmissions. Our exposure modeling approach can be used to evaluate and optimize mitigation procedures. PMID:24471782

  7. Increasing the maximally random jammed density with electric field to reduce the fat level in chocolate

    NASA Astrophysics Data System (ADS)

    Tao, R.; Tang, H.

    Chocolate is one of the most popular food types and flavors in the world. Unfortunately, at present, chocolate products contain too much fat, leading to obesity. For example, a typical molding chocolate has various fat up to 40% in total and chocolate for covering ice cream has fat 50 -60%. Especially, as children are the leading chocolate consumers, reducing the fat level in chocolate products to make them healthier is important and urgent. While this issue was called into attention and elaborated in articles and books decades ago and led to some patent applications, no actual solution was found unfortunately. Why is reducing fat in chocolate so difficult? What is the underlying physical mechanism? We have found that this issue is deeply related to the basic science of soft matters, especially to their viscosity and maximally random jammed (MRJ) density φx. All chocolate productions are handling liquid chocolate, a suspension with cocoa solid particles in melted fat, mainly cocoa butter. The fat level cannot be lower than 1-φxin order to have liquid chocolate to flow. Here we show that that with application of an electric field to liquid chocolate, we can aggregate the suspended particles into prolate spheroids. This microstructure change reduces liquid chocolate's viscosity along the flow direction and increases its MRJ density significantly. Hence the fat level in chocolate can be effectively reduced. We are looking forward to a new class of healthier and tasteful chocolate coming to the market soon. Dept. of Physics, Temple Univ, Philadelphia, PA 19122.

  8. Increased Prevalence of Esophageal Cancer in Areas with High Levels of Nickel in Farm Soils

    PubMed Central

    Lee, Chien-Pang; Lee, Yen-Hsin; Lian, Ie-Bin; Su, Che-Chun

    2016-01-01

    Background: Heavy metal pollution in farm soils is a grave concern in Taiwan. Previously, we found the incidence of oral cancer (OC) correlated positively with levels of nickel and arsenic in farm soils. Many OC patients have a second malignancy, among which esophageal cancer (EC) is the most common one in Taiwan. Objectives: We aimed to investigate whether these two cancers share some common risk factors. Methods: Taiwan began a compulsory national health insurance program in 1995. We used a database from this program to calculate the prevalence of EC and OC in Taiwan. We compared the prevalence of EC with prevalence of betel nut chewers in adults and the information of heavy metal in farm soils to look for any association. Results: The prevalence of OC and prevalence of EC were strongly correlated. The prevalence of betel nut chewing correlated with OC prevalence, but not with EC prevalence. An increased prevalence (1.9 fold) of EC was found where the farm soils contained high levels of nickel. Meanwhile, among the eight heavy metals studied, only the levels of nickel in the farm soils correlated statistically with the prevalence of EC. Conclusion: Nickel is probably a common environmental risk factor for esophageal cancer and oral cancer.

  9. Increased Prevalence of Esophageal Cancer in Areas with High Levels of Nickel in Farm Soils

    PubMed Central

    Lee, Chien-Pang; Lee, Yen-Hsin; Lian, Ie-Bin; Su, Che-Chun

    2016-01-01

    Background: Heavy metal pollution in farm soils is a grave concern in Taiwan. Previously, we found the incidence of oral cancer (OC) correlated positively with levels of nickel and arsenic in farm soils. Many OC patients have a second malignancy, among which esophageal cancer (EC) is the most common one in Taiwan. Objectives: We aimed to investigate whether these two cancers share some common risk factors. Methods: Taiwan began a compulsory national health insurance program in 1995. We used a database from this program to calculate the prevalence of EC and OC in Taiwan. We compared the prevalence of EC with prevalence of betel nut chewers in adults and the information of heavy metal in farm soils to look for any association. Results: The prevalence of OC and prevalence of EC were strongly correlated. The prevalence of betel nut chewing correlated with OC prevalence, but not with EC prevalence. An increased prevalence (1.9 fold) of EC was found where the farm soils contained high levels of nickel. Meanwhile, among the eight heavy metals studied, only the levels of nickel in the farm soils correlated statistically with the prevalence of EC. Conclusion: Nickel is probably a common environmental risk factor for esophageal cancer and oral cancer. PMID:27698910

  10. Modeling effectiveness of gradual increases in source level to mitigate effects of sonar on marine mammals.

    PubMed

    Von Benda-Beckmann, Alexander M; Wensveen, Paul J; Kvadsheim, Petter H; Lam, Frans-Peter A; Miller, Patrick J O; Tyack, Peter L; Ainslie, Michael A

    2014-02-01

    Ramp-up or soft-start procedures (i.e., gradual increase in the source level) are used to mitigate the effect of sonar sound on marine mammals, although no one to date has tested whether ramp-up procedures are effective at reducing the effect of sound on marine mammals. We investigated the effectiveness of ramp-up procedures in reducing the area within which changes in hearing thresholds can occur. We modeled the level of sound killer whales (Orcinus orca) were exposed to from a generic sonar operation preceded by different ramp-up schemes. In our model, ramp-up procedures reduced the risk of killer whales receiving sounds of sufficient intensity to affect their hearing. The effectiveness of the ramp-up procedure depended strongly on the assumed response threshold and differed with ramp-up duration, although extending the duration of the ramp up beyond 5 min did not add much to its predicted mitigating effect. The main factors that limited effectiveness of ramp up in a typical antisubmarine warfare scenario were high source level, rapid moving sonar source, and long silences between consecutive sonar transmissions. Our exposure modeling approach can be used to evaluate and optimize mitigation procedures.

  11. Neonatal alcohol exposure increases malondialdehyde (MDA) and glutathione (GSH) levels in the developing cerebellum.

    PubMed

    Smith, Andrew M; Zeve, Daniel R; Grisel, Jedidiah J; Chen, Wei-Jung A

    2005-12-01

    It has been suggested that developmental alcohol-induced brain damage is mediated through increases in oxidative stress. In this study, the concentrations of malondialdehyde (MDA) and reduced glutathione (GSH) were measured to indicate alcohol-mediated oxidative stress. In addition, the ability of two known antioxidants, melatonin (MEL) and lazaroid U-83836E (U), to attenuate alcohol-induced oxidative stress was investigated. Sprague-Dawley rat pups were randomly assigned to six artificially-reared groups, ALC (alcohol), MEL, MEL/ALC, U, U/ALC, and GC (gastrostomy control), and one normal suckle control (to control for artificial-rearing effects on the dependent variables). The daily dosages for ALC, MEL, and U were 6 g/kg, 20 mg/kg, and 20 mg/kg, respectively. Alcohol was administered in 2 consecutive feedings, and antioxidant (MEL or U) was administered for a total of 4 consecutive feedings (2 feedings prior to and 2 feedings concurrently with alcohol). The animals received treatment from postnatal days (PD) 4 through 9. Cerebellar, hippocampal, and cortical samples were collected on PD 9 and analyzed for MDA and GSH content. The results indicated that MDA concentrations in the cerebellum were significantly elevated in animals receiving alcohol; however, MDA levels in the hippocampus and cortex were not affected by alcohol treatment. Additionally, GSH levels in the cerebellum were significantly elevated in groups receiving alcohol, regardless of antioxidant treatment. Neither antioxidant was able to protect against alcohol-induced alterations of MDA or GSH. These findings suggest that alcohol might increase GSH levels indirectly as a compensatory mechanism designed to protect the brain from oxidative-stress-mediated insult.

  12. Increase of exhaled nitric oxide in children exposed to low levels of ambient ozone.

    PubMed

    Nickmilder, Marc; de Burbure, Claire; Carbonnelle, Sylviane; Sylviane, Carbonnelle; Dumont, Xavier; Xavier, Dumont; Bernard, Alfred; Alfred, Bernard; Derouane, Alain; Alain, Derouane

    2007-02-01

    Ozone (O3) is known to induce lung function impairment and airways inflammation during episodes of photochemical smog. The aim of the present study was to assess the inflammatory effect of ambient O3 in healthy children using nitric oxide in exhaled air (eNO) as a noninvasive test. The study was performed on 6 groups of children (n = 11-15), aged 6.5 to 15 yr, who attended summer camps in rural areas of the south of Belgium in 2002. Ambient O3 concentrations continuously monitored in the camps ranged from 48 to 221 microg/m3 (1-h maximal concentration). Children remained outdoors during the experimental days, doing various recreational activities but no sports. Lung function tests (forced expiratory volume in 1 s [FEV1] and forced vital capacity [FVC]) and eNO were measured twice in each child in the morning and in the evening. While lung function tests did not show any consistent pattern of decrease at these O3 levels, a highly significant increase in eNO was found in all subjects from an ambient 1-h O3 level of 167 microg/m3. A multivariate analysis did not reveal any influence of age, gender, height, weight, and body mass index (BMI) of the children. The threshold for this O3-induced increase in eNO estimated benchmark dose analysis was 135 microg/m3 for 1-h exposure and 110 microg/m3 for 8-h exposure. These observations suggest that ambient ozone produces early inflammatory changes in the airways of children at levels slightly below current air quality standards. PMID:17365589

  13. Increased cortisol levels in hair of recent Ecstasy/MDMA users.

    PubMed

    Parrott, A C; Sands, H R; Jones, L; Clow, A; Evans, P; Downey, L A; Stalder, T

    2014-03-01

    Previous research has revealed an acute 8-fold increase in salivary cortisol following self-administrated Ecstasy/MDMA in dance clubbers. It is currently not known to what extent repeated usage impacts upon activity of the hypothalamic-pituitary-adrenal axis over a more prolonged period of time. This study investigated the integrated cortisol levels in 3-month hair samples from recent Ecstasy/MDMA users and non-user controls. One hundred and one unpaid participants (53 males, 48 females; mean age 21.75 years) completed the University of East London recreational drug use questionnaire, modified to cover the past 3-months of usage. They comprised 32 light recent Ecstasy/MDMA users (1-4 times in last 3 months), 23 recent heavy MDMA users (+5 times in last 3 months), and 54 non-user controls. Volunteers provided 3 cm hair samples for cortisol analysis. Hair cortisol levels were observed to be significantly higher in recent heavy MDMA users (mean = 55.0 ± 80.1 pg/mg), compared to recent light MDMA users (19.4 ± 16.0 pg/mg; p=0.015), and to non-users (13.8 ± 6.1 pg/mg; p<0.001). Hence the regular use of Ecstasy/MDMA was associated with almost 4-fold raised hair cortisol levels, in comparison with non-user controls. The present results are consistent with the bio-energetic stress model for Ecstasy/MDMA, which predicts that repeated stimulant drug use may increase cortisol production acutely, and result in greater deposits of the hormone in hair. These data may also help explain the neurocognitive, psychiatric, and other psychobiological problems of some abstinent users. Future study design and directions for research concerning the psychoneuroendocrinological impact of MDMA are also discussed.

  14. Protection against UVA-induced photooxidative damage in mammalian cell lines expressing increased levels of metallothionein

    SciTech Connect

    Dudek, E.J. Illinois Inst. of Tech., Chicago, IL . Dept. of Biology); Peak, J.G.; Peak, M.J. ); Roth, R.M. . Dept. of Biology)

    1990-01-01

    Metallothionein (MT) is an endogenous low molecular weight protein that is inducible in a variety of eukaryotic cells and has the ability to selectivity bind heavy metal ions such as zinc and the cadmium. Although the exact physiological role of MT is still not understood, there is strong evidence that MT is involved in providing cellular resistance against the damaging effects of heavy metals and in the regulation of intracellular zinc and copper. Recently, it has been demonstrated that MT can scavenge radiation-induced reactive oxygen intermediates in vitro, specifically hydroxyl and superoxide radicals, and because of these observations it has been suggested that MT may provide protection against radiation-induced oxidative stress in vivo. Cell lines expressing increased levels of MT have demonstrated resistance to ionizing radiation, to ultraviolet radiation, and also to various DNA damaging agents including melphalan and cis-diaminedichloroplatinum. It is therefore important to gain some insight into the relationship between cellular MT content and cellular resistance to radiation and other DNA damaging agents. In this study we investigated the role of MT in providing protection against monochromatic 365-nm UVA radiation, which is known to generate intracellular reactive oxygen species that are involved in both DNA damage and cell killing. For this purpose, we used zinc acetate, a potent inducer of MT, to elevate MT levels in V79 Chinese hamster fibroblasts prior to UVA exposure and determined cell survival for uninduced and induced cultures. In order to eliminate any zinc effects other than MT induction, we also isolated and characterized cadmium chloride-resistant clones of V79 cells that have increased steady-state levels of both MT mRNA and protein, and we examined their survival characteristics against 365-nm radiation in the absence of zinc acetate. 14 refs., 3 figs.

  15. Modification of chitosan by swelling and crosslinking using epichlorohydrin as heavy metal Cr (VI) adsorbent in batik industry wastes

    NASA Astrophysics Data System (ADS)

    Hastuti, B.; Masykur, A.; Hadi, S.

    2016-02-01

    Study on chitosan modification by swelling and crosslinking and its application as a selective adsorbent for heavy metals Cr (VI) in batik industry wastes was done. Swelling is intended to improve chitosan porosity, whereas crosslinking is to increase the resistance of chitosan against acid. Natural samples are generally acidic, thus limiting chitosan application as an adsorbent. Modification of chitosan by combining swelling and crosslinking is expected to increase its adsorption capacity in binding heavy metal ions in water. The modified chitosan was later contacted with Cr (VI) to test its adsorption capacity with a variation of pH and contact time. Finally, application of modified chitosan was done in batik industry waste containing Cr (IV). Based on the results, chitosan-ECH 25% (v/v) was the optimum concentration of crosslinker to adsorb Cr (VI) ions. Modified chitosan has a solubility resistance to acids, even though a strong acid. Modification of chitosan also improved its adsorption capacity to Cr (VI) from 74% (pure chitosan) to 89% with contact time 30 min at pH 3. On the application to the batik wastes, the modified chitosan were able to adsorb Cr (IV) up to the level of 5 ppm. Thus, the modified chitosan has a potential to be applied to as an adsorbent of Cr (VI) in batik industry wastes.

  16. Exogenous t-PA Administration Increases Hippocampal Mature BDNF Levels. Plasmin- or NMDA-Dependent Mechanism?

    PubMed Central

    Rodier, Marion; Prigent-Tessier, Anne; Béjot, Yannick; Jacquin, Agnès; Mossiat, Claude; Marie, Christine; Garnier, Philippe

    2014-01-01

    Brain-derived neurotrophic factor (BDNF) through TrkB activation is central for brain functioning. Since the demonstration that plasmin is able to process pro-BDNF to mature BDNF and that these two forms have opposite effects on neuronal survival and plasticity, a particular attention has been paid to the link between tissue plasminogen activator (tPA)/plasmin system and BDNF metabolism. However, t-PA via its action on different N-methyl-D-aspartate (NMDA) receptor subunits is also considered as a neuromodulator of glutamatergic transmission. In this context, the aim of our study was to investigate the effect of recombinant (r)t-PA administration on brain BDNF metabolism in rats. In the hippocampus, we found that rt-PA (10 mg/kg) administration induced a progressive increase in mature BDNF levels associated with TrkB activation. In order to delineate the mechanistic involved, plasmin activity was assessed and its inhibition was attempted using tranexamic acid (30 or 300 mg/kg, i.v.) while NMDA receptors were antagonized with MK801 (0.3 or 3 mg/kg, i.p.) in combination with rt-PA treatment. Our results showed that despite a rise in rt-PA activity, rt-PA administration failed to increase hippocampal plasmin activity suggesting that the plasminogen/plasmin system is not involved whereas MK801 abrogated the augmentation in mature BDNF levels observed after rt-PA administration. All together, our results show that rt-PA administration induces increase in hippocampal mature BDNF expression and suggests that rt-PA contributes to the control of brain BDNF synthesis through a plasmin-independent potentiation of NMDA receptors signaling. PMID:24670989

  17. Exogenous t-PA administration increases hippocampal mature BDNF levels. plasmin- or NMDA-dependent mechanism?

    PubMed

    Rodier, Marion; Prigent-Tessier, Anne; Béjot, Yannick; Jacquin, Agnès; Mossiat, Claude; Marie, Christine; Garnier, Philippe

    2014-01-01

    Brain-derived neurotrophic factor (BDNF) through TrkB activation is central for brain functioning. Since the demonstration that plasmin is able to process pro-BDNF to mature BDNF and that these two forms have opposite effects on neuronal survival and plasticity, a particular attention has been paid to the link between tissue plasminogen activator (tPA)/plasmin system and BDNF metabolism. However, t-PA via its action on different N-methyl-D-aspartate (NMDA) receptor subunits is also considered as a neuromodulator of glutamatergic transmission. In this context, the aim of our study was to investigate the effect of recombinant (r)t-PA administration on brain BDNF metabolism in rats. In the hippocampus, we found that rt-PA (10 mg/kg) administration induced a progressive increase in mature BDNF levels associated with TrkB activation. In order to delineate the mechanistic involved, plasmin activity was assessed and its inhibition was attempted using tranexamic acid (30 or 300 mg/kg, i.v.) while NMDA receptors were antagonized with MK801 (0.3 or 3 mg/kg, i.p.) in combination with rt-PA treatment. Our results showed that despite a rise in rt-PA activity, rt-PA administration failed to increase hippocampal plasmin activity suggesting that the plasminogen/plasmin system is not involved whereas MK801 abrogated the augmentation in mature BDNF levels observed after rt-PA administration. All together, our results show that rt-PA administration induces increase in hippocampal mature BDNF expression and suggests that rt-PA contributes to the control of brain BDNF synthesis through a plasmin-independent potentiation of NMDA receptors signaling.

  18. Increased GABA Levels in Medial Prefrontal Cortex of Young Adults with Narcolepsy

    PubMed Central

    Kim, Seog Ju; Lyoo, In Kyoon; Lee, Yujin S.; Sung, Young Hoon; Kim, Hengjun J.; Kim, Jihyun H.; Kim, Kye Hyun; Jeong, Do-Un

    2008-01-01

    Study Objectives: To explore absolute concentrations of brain metabolites including gamma amino-butyric acid (GABA) in the medial prefrontal cortex and basal ganglia of young adults with narcolepsy. Design: Proton magnetic resonance (MR) spectroscopy centered on the medial prefrontal cortex and the basal ganglia was acquired. The absolute concentrations of brain metabolites including GABA and glutamate were assessed and compared between narcoleptic patients and healthy comparison subjects. Setting: Sleep and Chronobiology Center at Seoul National University Hospital; A high strength 3.0 Tesla MR scanner in the Department of Radiology at Seoul National University Hospital. Patients or Participants: Seventeen young adults with a sole diagnosis of HLA DQB1 0602 positive narcolepsy with cataplexy (25.1 ± 4.6 years old) and 17 healthy comparison subjects (26.8 ± 4.8 years old). Interventions: N/A. Measurements and Results: Relative to comparison subjects, narcoleptic patients had higher GABA concentration in the medial prefrontal cortex (t = 4.10, P <0.001). Narcoleptic patients with nocturnal sleep disturbance had higher GABA concentration in the medial prefrontal cortex than those without nocturnal sleep disturbance (t = 2.45, P= 0.03), but had lower GABA concentration than comparison subjects (t = 2.30, P = 0.03). Conclusions: The current study reports that young adults with narcolepsy had a higher GABA concentration in the medial prefrontal cortex, which was more prominent in patients without nocturnal sleep disturbance. Our findings suggest that the medial prefrontal GABA level may be increased in narcolepsy, and the increased medial prefrontal GABA might be a compensatory mechanism to reduce nocturnal sleep disturbances in narcolepsy. Citation: Kim SJ; Lyoo IK; Lee YS; Sung YH; Kim HJ; Kim JH; Kim KH; Jeong DU. Increased GABA levels in medial prefrontal cortex of young adults with narcolepsy. SLEEP 2008;31(3):342-347. PMID:18363310

  19. Characterization of glycidyl methacrylate – Crosslinked hyaluronan hydrogel scaffolds incorporating elastogenic hyaluronan oligomers

    PubMed Central

    Ibrahim, S.; Kothapalli, C.R.; Kang, Q.K.; Ramamurthi, A.

    2013-01-01

    Prior studies on two-dimensional cell cultures suggest that hyaluronic acid (HA) stimulates cell-mediated regeneration of extracellular matrix structures, specifically those containing elastin, though such biologic effects are dependent on HA fragment size. Towards being able to regenerate three-dimensional (3-D) elastic tissue constructs, the present paper studies photo-crosslinked hydrogels containing glycidyl methacrylate (GM)-derivatized bio-inert high molecular weight(HMW)HA (1 × 106 Da) and a bioactive HA oligomer mixture (HA-o: MW ~0.75 kDa). The mechanical (rheology, degradation) and physical (apparent crosslinking density, swelling ratio) properties of the gels varied as a function of incorporated HA oligomer content; however, overall, the mechanics of these hydrogels were too weak for vascular applications as stand-alone materials. Upon in vivo subcutaneous implantation, only a few inflammatory cells were evident around GM–HA gels, however their number increased as HA-o content within the gels increased, and the collagen I distribution was uniform. Smooth muscle cells (SMC) were encapsulated into GM hydrogels, and calcein acetoxymethyl detection revealed that the cells were able to endure twofold the level of UV exposure used to crosslink the gels. After 21 days of culture, SMC elastin production, measured by immunofluorescence quantification, showed HA-o to increase cellular deposition of elastic matrix twofold relative to HA-o-free GM–HAgels. These results demonstrate that cell response to HA/HA-o is not altered by their methacrylation and photo-crosslinking into a hydrogel, and that HA-o incorporation into cell-encapsulating hydrogel scaffolds can be useful for enhancing their production of elastic matrix structures in a 3-D space, important for regenerating elastic tissues. PMID:20709199

  20. Chemically crosslinked isoreticular metal-organic frameworks.

    PubMed

    Allen, Corinne A; Boissonnault, Jake A; Cirera, Jordi; Gulland, Ryan; Paesani, Francesco; Cohen, Seth M

    2013-04-21

    Herein we report the synthesis of canonical isoreticular metal-organic frameworks (IRMOFs) containing interligand crosslinks. Chemically crosslinking two molecules of 2-amino-1,4-benzene dicarboxylic acid (NH2-BDC) gives ligands that readily form IRMOF-1 analogs, producing crosslinked MOFs that may be designed to have novel properties.

  1. Electrospinning formaldehyde cross-linked zein solutions

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In order to develop zein fibers with improved physical properties and solvent resistance, formaldehyde was used as the cross-linking reagent before spinning. The cross-linking reaction was carried out in either acetic acid or ethanolic-HCl where the amount of cross-linking reagent was between 1 and...

  2. Progesterone inhibits behavioral responses and estrogen increases corticosterone levels after acute cocaine administration.

    PubMed

    Niyomchai, Tipyamol; Russo, Scott J; Festa, Eugene D; Akhavan, Alaleh; Jenab, Shirzad; Quiñones-Jenab, Vanya

    2005-04-01

    Accumulating evidence suggests that estrogen and progesterone contribute to the sexually dimorphic behavioral response to cocaine. In this study, we tested the hypothesis that varying the level of estrogen or progesterone affects cocaine-induced locomotive behavior in female rats. Ovariectomized (OVX) rats received estrogen (0, 5, 10, 20, or 50 microg) 48 h or progesterone (0, 50, 100, 250, or 500 microg) 24 h before acute saline or cocaine (15 mg/kg) administration. Although estrogen did not affect cocaine-induced ambulatory and rearing behaviors, it affected stereotypic behaviors regardless of cocaine administration (animals receiving 50 microg had higher stereotypic counts than did the OVX group). In contrast, progesterone affected rearing activity dose-dependently: 50 and 500 microg of progesterone inhibited, whereas 100 microg and 250 microg stimulated, rearing in response to cocaine. That estrogen and progesterone did not affect overall baseline behavioral activity suggests their effects are mediated in part through interactions with cocaine. Progesterone administration did not affect corticosterone levels in saline- or cocaine-treated rats. Estrogen administration, however, affected levels of corticosterone both at baseline and after cocaine treatment. After accounting for baseline differences, we found that rats receiving 5 or 10 microg of estrogen and cocaine had higher percentage increases in serum corticosterone levels than did the control group that did not receive estrogen. On the basis of these observations, we suggest that progesterone fluctuations during the estrous cycle impact cocaine-induced behavioral responses, whereas estrogen may affect activity in the hypothalamic-pituitary-adrenal axis. Thus, dose-dependent effects of gonadal hormones may underlie some of the reported sex differences and reproductive cycle effects of cocaine.

  3. Production performance, stress tolerance and intestinal integrity of sunshine bass fed increasing levels of soybean meal.

    PubMed

    Laporte, J; Trushenski, J

    2012-06-01

    Soybean meal (SBM) is perhaps the most common fish meal (FM) alternative used in aquafeeds; however, SBM cannot fully replace FM in sunshine bass Morone chrysops × M. saxatilis feeds without impacting growth. Reduced production performance may be the result of subtle changes in morphology and/or physiological status. Accordingly, our objective was to assess growth, gastrointestinal integrity and stress tolerance of sunshine bass fed increasing amounts of SBM. Fish (approximately 14.5 g) were fed diets (14% lipid and 40% protein) containing increasing amounts of SBM at the expense of FM (30% FM, 20% FM, 15% FM, 10% FM, 5% FM and 0% FM) for 8 weeks. As expected, complete replacement of FM reduced growth. Although some signs of enteritis were noted, no significant differences in gut integrity were observed. Following 15-min low-water stress challenge, plasma glucose levels were elevated, particularly among fish fed increasing amounts of SBM. Cortisol response was similar, but statistical differences were not resolved for this parameter. Completely replacing FM in feeds for sunshine bass elicits overt reductions in growth. More subtle physiological changes may also result from FM replacement, including alterations in stress tolerance, and these may be important to consider in terms of the suitability of aquafeed formulations and optimal nutrition of sunshine bass.

  4. Increased amounts of the influenza virus nucleoprotein do not promote higher levels of viral genome replication.

    PubMed

    Mullin, Anne E; Dalton, Rosa M; Amorim, Maria Joao; Elton, Debra; Digard, Paul

    2004-12-01

    Influenza virus genome replication requires the virus-encoded nucleoprotein (NP), partly because it is necessary to encapsidate the viral genomic RNA (vRNA) and antigenomic cRNA segments into ribonucleoproteins (RNPs). However, there is also evidence that NP actively regulates viral RNA synthesis and there is a long-standing hypothesis that increased concentrations of NP in the cell are responsible for a switch from genome transcription to replication. Here, this hypothesis is tested in a recombinant setting and in the context of virus infection. In a plasmid-based system for reconstituting active viral RNPs in cells, titration of increasing amounts of NP did not promote higher levels of genome replication relative to transcription, but in fact caused the opposite effect. An approximately fourfold reduction in the ratio of genomic and antigenomic RNAs to mRNA was seen across an 80-fold range of NP plasmid concentrations. When cells were transfected with the same amounts of NP plasmid to establish a concentration gradient of NP prior to virus superinfection, no change in the ratio of cRNA to mRNA was seen for segments 5 and 7, or for the ratio of segment 5 vRNA to mRNA. A slight reduction in the ratio of segment 7 vRNA to mRNA was seen. These findings do not support the simple hypothesis that increased intracellular concentrations of NP promote influenza virus genome replication.

  5. Risk of cancer in an occupationally exposed cohort with increased level of chromosomal aberrations.

    PubMed Central

    Smerhovsky, Z; Landa, K; Rössner, P; Brabec, M; Zudova, Z; Hola, N; Pokorna, Z; Mareckova, J; Hurychova, D

    2001-01-01

    We used cytogenetic analysis to carry out a cohort study in which the major objective was to test the association between frequency of chromosomal aberrations and subsequent risk of cancer. In spite of the extensive use of the cytogenetic analysis of human peripheral blood lymphocytes in biomonitoring of exposure to various mutagens and carcinogens on an ecologic level, the long-term effects of an increased frequency of chromosomal aberrations in individuals are still uncertain. Few epidemiologic studies have addressed this issue, and a moderate risk of cancer in individuals with an elevated frequency of chromosomal aberrations has been observed. In the present study, we analyzed data on 8,962 cytogenetic tests and 3,973 subjects. We found a significant and strong association between the frequency of chromosomal aberrations and cancer incidence in a group of miners exposed to radon, where a 1% increase in frequency of chromosomal aberrations was followed by a 64% increase in risk of cancer (p < 0.000). In contrast, the collected data are inadequate for a critical evaluation of the association with exposure to other chemicals. PMID:11171523

  6. Increased Levels of Sphingosylphosphorylcholine (SPC) in Plasma of Metabolic Syndrome Patients.

    PubMed

    El-Najjar, Nahed; Orsó, Evelyn; Wallner, Stefan; Liebisch, Gerhard; Schmitz, Gerd

    2015-01-01

    Recent developments in lipid mass spectrometry enable extensive lipid class and species analysis in metabolic disorders such as diabesity and metabolic syndrome. The minor plasma lipid class sphingosylphosphorylcholine (SPC) was identified as a ligand for lipid sensitive G-protein coupled receptors playing a key role in cell growth, differentiation, motility, calcium signaling, tissue remodeling, vascular diseases and cancer. However, information about its role in diabesity patients is sparse. In this study, we analyzed plasma lipid species in patients at risk for diabesity and the metabolic syndrome and compared them with healthy controls. Our data show that SPC is significantly increased in plasma samples from metabolic syndrome patients but not in plasma from patients at risk for diabesity. Detailed SPC species analysis showed that the observed increase is due to a significant increase in all detected SPC subspecies. Moreover, a strong positive correlation is observed between total SPC and individual SPC species with both body mass index and the acute phase low grade inflammation marker soluble CD163 (sCD163). Collectively, our study provides new information on SPC plasma levels in metabolic syndrome and suggests new avenues for investigation. PMID:26466367

  7. Increased resistance to free radical damage induced by low-level sound conditioning.

    PubMed

    Harris, Kelly Carney; Bielefeld, Eric; Hu, Bo Hua; Henderson, Donald

    2006-03-01

    Conditioning is the phenomenon where exposure to moderate-level acoustic stimuli can increase the ear's resistance to subsequent more intense sound exposures. In recent years, research has shown that conditioning increases the availability of antioxidant enzymes which presumably protects the ear from oxidative stress induced by a traumatic noise exposure [Jacono, A.A., Hu, B., Kopke, R.D., Henderson, D., Van De Water, T.R., Steinman, H.M., 1998. Changes in cochlear antioxidant enzyme activity after sound conditioning and noise exposure in the chinchilla. Hear Res 117, 31-8]. The current study was designed to assess whether the increase in endogenous antioxidants seen following conditioning could provide protection from oxidative stress induced by Paraquat, a potent generator of superoxide. Chinchillas were exposed to a conditioning noise, 500 Hz OBN at 95 dB for 6 h/day for 10 days, followed 5 days later with Paraquat application to the round window. Controls underwent the Paraquat application surgery, without prior conditioning. Evoked potential thresholds were determined prior to conditioning, at day 1, 5 and 10 during conditioning, at day 15 (5 days after conditioning), and at day 17, 19, 23, and 35 (1, 3, 7, and 20 days post-Paraquat). The conditioned animals showed reductions in permanent threshold shift and reduced inner hair cell loss relative to controls. These results reinforce the hypothesis that antioxidants are primary mediators of the conditioning effect.

  8. Effect of radiation cross-linking on the abrasive wear behaviour of polyethylenes

    NASA Astrophysics Data System (ADS)

    Gul, Rizwan M.; Khan, Tahir I.

    2014-06-01

    This study explores the differences in the dry abrasive wear behavior of different polyethylenes, and compares the effect of radiation cross-linking on the wear behavior. Four different types of polyethylenes: LDPE, LLDPE, HDPE and UHMWPE were studied. Cross-linking was carried out by high energy electron beam with radiation dose of 200 kGy. The results show that in unirradiated state UHMWPE has excellent wear resistance, with HDPE showing comparable wear properties; both LDPE and LLDPE exhibit high wear rate. Cross-linking improves wear rate of LDPE and UHMWPE, however, the wear rate of HDPE and LLDPE increases with cross-linking.

  9. Increased levels of interleukins 8 and 10 as findings of canine inflammatory mammary cancer.

    PubMed

    de Andrés, Paloma Jimena; Illera, Juan Carlos; Cáceres, Sara; Díez, Lucía; Pérez-Alenza, Maria Dolores; Peña, Laura

    2013-04-15

    Inflammatory mammary cancer (IMC) is a distinct form of mammary cancer that affects dogs and women [in humans, IMC is known as inflammatory breast cancer (IBC)], and is characterized by a sudden onset and an aggressive clinical course. Spontaneous canine IMC shares epidemiologic, histopathological and clinical characteristics with the disease in humans and has been proposed as the best spontaneous animal model for studying IBC, although several aspects remain unstudied. Interleukins (ILs) play an important role in cancer as potential modulators of angiogenesis, leukocyte infiltration and tumor growth. The aims of the present study were to assess serum and tumor levels of several ILs (IL-1α, IL-1β, IL-6, IL-8 and IL-10) by enzyme-immunoassay in dogs bearing benign and malignant mammary tumors, including dogs with IMC, for a better understanding of this disease. Forty-eight dogs were prospectively included. Animals consisted of 7 healthy Beagles used as donors for normal mammary glands (NMG) and serum controls (SCs), 10 dogs with hyperplasias and benign mammary tumors (HBMT), 24 with non-inflammatory malignant mammary tumors (non-IMC MMT) and 7 dogs with clinical and pathological IMC. IL-8 (serum) and IL-10 (serum and tissue homogenate) levels were higher in the dogs with IMC compared with the non-IMC MMT group. ILs were increased with tumor malignancy as follows: in tumor homogenates IL-6 levels were higher in malignant tumors (IMC and non-IMC MMT) versus HBMT and versus NMG and tumor IL-8 was increased in malignant tumors versus NMG; in serum, IL-1α and IL-8 levels were higher in the malignant groups respect to HBMT and SCs; interestingly, IL-10 was elevated only in the serum of IMC animals. To the best of our knowledge, this is the first report that analyzes ILs in IMC and IL-10 in canine mammary tumors. Our results indicate a role for IL-6, IL-8 and IL-10 in canine mammary malignancy and specific differences in ILs content in IMC versus non-IMC MMT that could

  10. Increased levels of interleukins 8 and 10 as findings of canine inflammatory mammary cancer.

    PubMed

    de Andrés, Paloma Jimena; Illera, Juan Carlos; Cáceres, Sara; Díez, Lucía; Pérez-Alenza, Maria Dolores; Peña, Laura

    2013-04-15

    Inflammatory mammary cancer (IMC) is a distinct form of mammary cancer that affects dogs and women [in humans, IMC is known as inflammatory breast cancer (IBC)], and is characterized by a sudden onset and an aggressive clinical course. Spontaneous canine IMC shares epidemiologic, histopathological and clinical characteristics with the disease in humans and has been proposed as the best spontaneous animal model for studying IBC, although several aspects remain unstudied. Interleukins (ILs) play an important role in cancer as potential modulators of angiogenesis, leukocyte infiltration and tumor growth. The aims of the present study were to assess serum and tumor levels of several ILs (IL-1α, IL-1β, IL-6, IL-8 and IL-10) by enzyme-immunoassay in dogs bearing benign and malignant mammary tumors, including dogs with IMC, for a better understanding of this disease. Forty-eight dogs were prospectively included. Animals consisted of 7 healthy Beagles used as donors for normal mammary glands (NMG) and serum controls (SCs), 10 dogs with hyperplasias and benign mammary tumors (HBMT), 24 with non-inflammatory malignant mammary tumors (non-IMC MMT) and 7 dogs with clinical and pathological IMC. IL-8 (serum) and IL-10 (serum and tissue homogenate) levels were higher in the dogs with IMC compared with the non-IMC MMT group. ILs were increased with tumor malignancy as follows: in tumor homogenates IL-6 levels were higher in malignant tumors (IMC and non-IMC MMT) versus HBMT and versus NMG and tumor IL-8 was increased in malignant tumors versus NMG; in serum, IL-1α and IL-8 levels were higher in the malignant groups respect to HBMT and SCs; interestingly, IL-10 was elevated only in the serum of IMC animals. To the best of our knowledge, this is the first report that analyzes ILs in IMC and IL-10 in canine mammary tumors. Our results indicate a role for IL-6, IL-8 and IL-10 in canine mammary malignancy and specific differences in ILs content in IMC versus non-IMC MMT that could

  11. Theory of crosslinked bundles of helical filaments: intrinsic torques in self-limiting biopolymer assemblies.

    PubMed

    Heussinger, Claus; Grason, Gregory M

    2011-07-21

    Inspired by the complex influence of the globular crosslinking proteins on the formation of biofilament bundles in living organisms, we study and analyze a theoretical model for the structure and thermodynamics of bundles of helical filaments assembled in the presence of crosslinking molecules. The helical structure of filaments, a universal feature of biopolymers such as filamentous actin, is shown to generically frustrate the geometry of crosslinking between the "grooves" of two neighboring filaments. We develop a coarse-grained model to investigate the interplay between the geometry of binding and mechanics of both linker and filament distortion, and we show that crosslinking in parallel bundles of helical filaments generates intrinsic torques, of the type that tend to wind the bundle superhelically about its central axis. Crosslinking mediates a non-linear competition between the preference for bundle twist and the size-dependent mechanical cost of filament bending, which in turn gives rise to feedback between the global twist of self-assembled bundles and their lateral size. Finally, we demonstrate that above a critical density of bound crosslinkers, twisted bundles form with a thermodynamically preferred radius that, in turn, increases with a further increase in crosslinking bonds. We identify the stiffness of crosslinking bonds as a key parameter governing the sensitivity of bundle structure and assembly to the availability and affinity of crosslinkers.

  12. Swelling of cross-linked polystyrene spheres in toluene vapor

    SciTech Connect

    Zhang, R.; Graf, K.; Berger, R.

    2006-11-27

    The swelling behavior of individual micron-sized polystyrene (PS) spheres in toluene vapor was studied via mass loading by means of micromechanical cantilever sensors. For 4%-8% cross-linked PS a mass increase of 180% in saturated toluene vapor was measured. The mass of the swollen PS sphere decreases with increasing exposure time to ultraviolet light. In addition, the swelling response is significantly different between the first and the second exposure to toluene vapor. This is attributed to the formation of a cross-linked shell at the surface of the PS spheres. Shape persistent parts were observed for locally irradiated PS spheres.

  13. Sea-Level Anomalies Facilitate Beach Erosion and Increase Barrier Island Vulnerability to Storms and Sea-Level Rise

    NASA Astrophysics Data System (ADS)

    Theuerkauf, E. J.; Rodriguez, A. B.; Fegley, S. R.; Luettich, R. A., Jr.

    2014-12-01

    Sea-level anomalies are intra-seasonal (weeks to months) periods of high water level induced by oceanographic and meteorological processes, such as reduced Gulf Stream transport strength or persistent northeasterly winds. Although flooding associated with sea-level anomalies has been documented along continental coastlines (e.g. U.S. East Coast), these phenomena are not presently included in coastal models and management plans. We present the first measurements of beach erosion after a year with frequent sea-level anomalies. Erosion during this year, which was not impacted by large storms, was similar to a year with a hurricane, indicating that sea-level anomalies are important facilitators of coastal erosion. Beach erosion was measured at Onslow Beach, NC (OB) in a year with frequent sea-level anomalies (2009-2010) and compared to erosion during a year with no major events (2010-2011) and the year with Hurricane Irene (2011-2012). Sea-level anomalies were identified in water level data from a NOAA tide gauge in Wrightsville Beach, NC. From 2009-2010 anomalously high sea level occurred ~40% of the time, compared to ~8% from 2010-2011 and ~10% from 2011-2012. Significant wave heights, measured from an acoustic wave and current profiler and NOAA buoys offshore of OB, were not statistically different among these 3 years. The average backshore, high intertidal, and mid intertidal maximum depth of erosion for all sites along OB in the year with frequent sea-level anomalies were ~25, 50, and 55 cm, respectively. These values are greater than those measured after the year with no major events (~13, 29, and 32 cm) and similar to those measured after the year with Hurricane Irene (~27, 49, and 40 cm). OB has high along-strike variability in barrier island morphology, thus results apply to many beaches and barrier islands. Our results suggest that anomalies are important mechanisms of coastal change and likely amplify erosion in response to accelerated sea-level rise and

  14. Increased copper levels in in vitro and in vivo models of Niemann-Pick C disease.

    PubMed

    Vázquez, Mary Carmen; Martínez, Pablo; Alvarez, Alejandra R; González, Mauricio; Zanlungo, Silvana

    2012-08-01

    Niemann-Pick type C disease (NPC) is a hereditary neurovisceral atypical lipid storage disorder produced by mutations in the NPC1 and NPC2 genes. The disease is characterized by unesterified cholesterol accumulation in late endosomal/lysosomal compartments and oxidative stress. The most affected tissues are the cerebellum and the liver. The lysotropic drug U18666A (U18) has been widely used as a pharmacological model to induce the NPC phenotype in several cell culture lines. It has already been reported that there is an increase in copper content in hepatoma Hu7 cells treated with U18. We confirmed this result with another human hepatoma cell line, HepG2, treated with U18 and supplemented with copper in the media. However, in mouse hippocampal primary cultures treated under similar conditions, we did not find alterations in copper content. We previously reported increased copper content in the liver of Npc1 (-/-) mice compared to control animals. Here, we extended the analysis to the copper content in the cerebella, the plasma and the bile of NPC1 deficient mice. We did not observe a significant change in copper content in the cerebella, whereas we found increased copper content in the plasma and decreased copper levels in the bile of Npc1(-/-) mice. Finally, we also evaluated the plasma content of ceruloplasmin, and we found an increase in this primary copper-binding protein in Npc1 (-/-) mice. These results indicate cell-type dependence of copper accumulation in NPC disease and suggest that copper transport imbalance may be relevant to the liver pathology observed in NPC disease.

  15. Ketoconazole increases fingolimod blood levels in a drug interaction via CYP4F2 inhibition.

    PubMed

    Kovarik, John M; Dole, Kiran; Riviere, Gilles-Jacques; Pommier, Francoise; Maton, Steve; Jin, Yi; Lasseter, Kenneth C; Schmouder, Robert L

    2009-02-01

    The sphingosine-1-phosphate receptor modulator fingolimod is predominantly hydroxylated by cytochrome CYP4F2. In vitro experiments showed that ketoconazole significantly inhibited the oxidative metabolism of fingolimod by human liver microsomes and by recombinant CYP4F2. The authors used ketoconazole as a putative CYP4F2 inhibitor to quantify its influence on fingolimod pharmacokinetics in healthy subjects. In a 2-period, single-sequence, crossover study, 22 healthy subjects received a single 5-mg dose of fingolimod in period 1. In period 2, subjects received ketoconazole 200 mg twice daily for 9 days and a single 5-mg dose of fingolimod coadministered on the 4th day of ketoconazole treatment. Ketoconazole did not affect fingolimod t(max) or half-life, but there was a weak average increase in C(max) of 1.22-fold (90% confidence interval, 1.15-1.30). The AUC over the 5 days of ketoconazole coadministration increased 1.40-fold (1.31-1.50), and the full AUC to infinity increased 1.71-fold (1.53-1.91). The AUC of the active metabolite fingolimod-phosphate was increased to a similar extent by 1.67-fold (1.50-1.85). Ketoconazole predose plasma levels were not altered by fingolimod. The magnitude of this interaction suggests that a proactive dose reduction of fingolimod is not necessary when adding ketoconazole to a fingolimod regimen. The clinician, however, should be aware of this interaction and bear in mind the possibility of a fingolimod dose reduction based on clinical monitoring. PMID:19118083

  16. Synthesis of borate cross-linked rhamnogalacturonan II.

    PubMed

    Funakawa, Hiroya; Miwa, Kyoko

    2015-01-01

    In the present review, we describe current knowledge about synthesis of borate crosslinked rhamnogalacturonan II (RG-II) and it physiological roles. RG-II is a portion of pectic polysaccharide with high complexity, present in primary cell wall. It is composed of homogalacturonan backbone and four distinct side chains (A-D). Borate forms ester bonds with the apiosyl residues of side chain A of two RG-II monomers to generate borate dimerized RG-II, contributing for the formation of networks of pectic polysaccharides. In plant cell walls, more than 90% of RG-II are dimerized by borate under boron (B) sufficient conditions. Borate crosslinking of RG-II in primary cell walls, to our knowledge, is the only experimentally proven molecular function of B, an essential trace-element. Although abundance of RG-II and B is quite small in cell wall polysaccharides, increasing evidence supports that RG-II and its borate crosslinking are critical for plant growth and development. Significant advancement was made recently on the location and the mechanisms of RG-II synthesis and borate cross-linking. Molecular genetic studies have successfully identified key enzymes for RG-II synthesis and regulators including B transporters required for efficient formation of RG-II crosslinking and consequent normal plant growth. The present article focuses recent advances on (i) RG-II polysaccharide synthesis, (ii) occurrence of borate crosslinking and (iii) B transport for borate supply to RG-II. Molecular mechanisms underlying formation of borate RG-II crosslinking and the physiological impacts are discussed. PMID:25954281

  17. Stimulation of border cell production in response to increased carbon dioxide levels.

    PubMed

    Zhao, X; Misaghi, I J; Hawes, M C

    2000-01-01

    Field soil atmospheres have higher CO(2) and lower O(2) concentrations compared with ambient atmosphere, but little is known about the impact of such conditions on root exudation patterns. We used altered levels of CO(2) and O(2) relative to ambient conditions to examine the influence of the atmosphere on the production of root border cells by pea (Pisum sativum) root tips. During germination, atmospheres with high CO(2) and low O(2) inhibited root development and border cell separation in pea seedlings. Later in development, the same atmospheric composition stimulated border cell separation without significantly influencing root growth. Increased CO(2), not low O(2), was responsible for the observed stimulation of border cell number. High CO(2) apparently can override endogenous signals that regulate the number of border cells released from pea roots into the rhizosphere. The same conditions that stimulated border cell production in pea had no such effect in alfalfa (Medicago sativa).

  18. Spectral Library Searching To Identify Cross-Linked Peptides.

    PubMed

    Schweppe, Devin K; Chavez, Juan D; Navare, Arti T; Wu, Xia; Ruiz, Bianca; Eng, Jimmy K; Lam, Henry; Bruce, James E

    2016-05-01

    Methods harnessing protein cross-linking and mass spectrometry (XL-MS) offer high-throughput means to identify protein-protein interactions (PPIs) and structural interfaces of protein complexes. Yet, specialized data dependent methods and search algorithms are often required to confidently assign peptide identifications to spectra. To improve the efficiency of matching high confidence spectra, we developed a spectral library based approach to search cross-linked peptide data derived from Protein Interaction Reporter (PIR) methods using the spectral library search algorithm, SpectraST. Spectral library matching of cross-linked peptide data from query spectra increased the absolute number of confident peptide relationships matched to spectra and thereby the number of PPIs identified. By matching library spectra from bona fide, previously established PIR-cross-linked peptide relationships, spectral library searching reduces the need for continued, complex mass spectrometric methods to identify peptide relationships, increases coverage of relationship identifications, and improves the accessibility of XL-MS technologies.

  19. Increase in upper tropospheric and lower stratospheric aerosol levels and its potential connection with Asian pollution

    PubMed Central

    Vernier, J-P; Fairlie, T D; Natarajan, M; Wienhold, F G; Bian, J; Martinsson, B G; Crumeyrolle, S; Thomason, L W; Bedka, K M

    2015-01-01

    Satellite observations have shown that the Asian Summer Monsoon strongly influences the upper troposphere and lower stratosphere (UTLS) aerosol morphology through its role in the formation of the Asian Tropopause Aerosol Layer (ATAL). Stratospheric Aerosol and Gas Experiment II solar occultation and Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observation (CALIPSO) lidar observations show that summertime UTLS Aerosol Optical Depth (AOD) between 13 and 18 km over Asia has increased by three times since the late 1990s. Here we present the first in situ balloon measurements of aerosol backscatter in the UTLS from Western China, which confirm high aerosol levels observed by CALIPSO since 2006. Aircraft in situ measurements suggest that aerosols at lower altitudes of the ATAL are largely composed of carbonaceous and sulfate materials (carbon/sulfur elemental ratio ranging from 2 to 10). Back trajectory analysis from Cloud-Aerosol Lidar with Orthogonal Polarization observations indicates that deep convection over the Indian subcontinent supplies the ATAL through the transport of pollution into the UTLS. Time series of deep convection occurrence, carbon monoxide, aerosol, temperature, and relative humidity suggest that secondary aerosol formation and growth in a cold, moist convective environment could play an important role in the formation of ATAL. Finally, radiative calculations show that the ATAL layer has exerted a short-term regional forcing at the top of the atmosphere of −0.1 W/m2 in the past 18 years. Key Points Increase of summertime upper tropospheric aerosol levels over Asia since the 1990s Upper tropospheric enhancement also observed by in situ backscatter measurements Significant regional radiative forcing of −0.1 W/m2 PMID:26691186

  20. Microzooplankton grazing and phytoplankton growth in marine mesocosms with increased CO2 levels

    NASA Astrophysics Data System (ADS)

    Suffrian, K.; Simonelli, P.; Nejstgaard, J. C.; Putzeys, S.; Carotenuto, Y.; Antia, A. N.

    2008-08-01

    Microzooplankton grazing and algae growth responses to increasing pCO2 levels (350, 700 and 1050 μatm) were investigated in nitrate and phosphate fertilized mesocosms during the PeECE III experiment 2005. Grazing and growth rates were estimated by the dilution technique combined with taxon specific HPLC pigment analysis. Microzooplankton composition was determined by light microscopy. Despite a range of up to 3 times the present CO2 levels, there were no clear differences in any measured parameter between the different CO2 treatments. During days 3 9 of the experiment the algae community standing stock, measured as chlorophyll a (Chl-a), showed the highest instantaneous grow rates (k=0.37 0.99 d-1) and increased from ca. 2 3 to 6 12 μg l-1, in all mesocosms. Afterwards the phytoplankton standing stock decreased in all mesocosms until the end of the experiment. The microzooplankton standing stock, that was mainly constituted by dinoflagellates and ciliates, varied between 23 and 130 μg C l-1 (corresponding to 1.9 and 10.8 μmol C l-1), peaking on day 13 15, apparently responding to the phytoplankton development. Instantaneous Chl-a growth rates were generally higher than the grazing rates, indicating only a limited overall effect of microzooplankton grazing on the most dominant phytoplankton. Diatoms and prymnesiophytes were significantly grazed (12 43% of the standing stock d-1) only in the pre-bloom phase when they were in low numbers, and in the post-bloom phase when they were already affected by low nutrients and/or viral lysis. The cyanobacteria populations appeared more affected by microzooplankton grazing which generally removed 20 65% of the standing stock per day.

  1. Microzooplankton grazing and phytoplankton growth in marine mesocosms with increased CO2 levels

    NASA Astrophysics Data System (ADS)

    Suffrian, K.; Simonelli, P.; Nejstgaard, J. C.; Putzeys, S.; Carotenuto, Y.; Antia, A. N.

    2008-01-01

    Microzooplankton grazing and algae growth responses to increasing pCO2 levels (350, 700 and 1050 μatm) were investigated in nitrate and phosphate fertilized mesocosms during the PeECE III experiment 2005. Grazing and growth rates were estimated by the dilution technique combined with taxon specific HPLC pigment analysis. Phytoplankton and microzooplankton composition were determined by light microscopy. Despite a range up to 3 times the present CO2 levels, there were no clear differences in any measured parameter between the different CO2 treatments. Thus, during the first 9 days of the experiment the algae community standing stock (SS), measured as chlorophyll a (Chl a), showed the highest instantaneous grow rates (0.02-0.99 d-1) and increased from ca 2-3 to 6-12 μg l-1, in all mesocosms. Afterwards the phytoplankton SS decreased in all mesocosms until the end of the experiment. The microzooplankton SS, that was mainly dinoflagellates and ciliates varied between 23 and 130 μg C l-1, peaking on day 13-15, apparently responding to the phytoplankton development. Instantaneous Chl a growth rates were generally higher than the grazing rates, indicating only a limited overall effect of microzooplankton grazing on the most dominant phytoplankton. Diatoms and prymnesiophytes were significantly grazed (14-43% of the SS d-1) only in the pre-bloom phase when they were in low numbers and in the post-bloom phase when they were already limited by low nutrients and/or virus lysis. The cyanobacteria populations appeared more effected by microzooplankton grazing, generally removing 20-65% of the SS d-1.

  2. Enterostatin decreases postprandial pancreatic UCP2 mRNA levels and increases plasma insulin and amylin.

    PubMed

    Arsenijevic, Denis; Gallmann, Eva; Moses, William; Lutz, Thomas; Erlanson-Albertsson, Charlotte; Langhans, Wolfgang

    2005-07-01

    This study investigated the chronic effect of enterostatin on body weight and some of the associated changes in postprandial metabolism. Rats were adapted to 6 h of food access/day and a choice of low-fat and high-fat (HF) food and then given enterostatin or vehicle by an intraperitoneally implanted minipump delivering 160 nmol enterostatin/h continuously over a 5-day infusion period. Enterostatin resulted in a slight but significant reduction of HF intake and body weight. After the last 6-h food access period, enterostatin-treated animals had lower plasma triglyceride and free fatty acid but higher plasma glucose and lactate levels than control animals. Enterostatin infusion resulted in increased uncoupling protein-2 (UCP2) expression in various tissues, including epididymal fat and liver. UCP2 was reduced in the pancreas of enterostatin-treated animals, and this was associated with increased plasma levels of insulin and amylin. Whether these two hormones are involved in the observed decreased food intake due to enterostatin remains to be determined. As lipid metabolism appeared to be altered by enterostatin, we measured peroxisome proliferator-activated receptor (PPAR) expression in tissues and observed that PPARalpha, -beta, -gamma1, and -gamma2 expression were modified by enterostatin in epididymal fat, pancreas, and liver. This further links altered lipid metabolism with body weight loss. Our data suggest that alterations in UCP2 and PPARgamma2 play a role in the control of insulin and amylin release from the pancreas. This implies that enterostatin changes lipid and carbohydrate metabolic pathways in addition to its effects on food intake and energy expenditure. PMID:15713687

  3. Blood SC5b-9 complement levels increase at parturition during term and preterm labor.

    PubMed

    Segura-Cervantes, Enrique; Mancilla-Ramirez, Javier; Zurita, Luis; Paredes, Yuriria; Arredondo, José Luis; Galindo-Sevilla, Norma

    2015-06-01

    We explored the hypothesis that complement, an innate and adaptive immune effector, is active in the plasma of parturient women and is deposited on fetal membranes collected after delivery. A cross-sectional study was designed to evaluate complement activity at parturition. Pregnant women (n = 97) between 15 and 41 years of age were enrolled in a hospital protocol during the perinatal period to assess both SC5b-9 complement activity in blood and complement deposition on fetal membranes during parturition. Soluble SC5b-9 complement activity in plasma fractions was measured using a standard enzyme-linked immunosorbent assay (ELISA) that included specific anti-complement antibodies. Complement deposition on membranes was analyzed using immuno-dot blots and immunohistochemistry. Soluble SC5b-9 complement complex levels were increased in the plasma of women during term labor (TL; median 3361; range 1726-5670 ng/mL), preterm labor (PL; median 2958; range 1552-7092 ng/mL), and preterm premature rupture of membranes (PPROM; median 2272; range 167-6540 ng/mL) compared with pregnant women who were not in labor (P; median 1384; range 174-4570 ng/mL; P < 0.001, Kruskal-Wallis test). Active complement, as assessed by the C9 neo-antigen in C5b-9 complexes, was deposited on fetal membranes, with no difference between term and preterm delivery. The deposition of active complement on fetal membranes was confirmed by immunohistochemistry. Women who underwent non-labor-indicated Cesarean sections did not exhibit complement deposition. Soluble SC5b-9 complement complex levels increased in the plasma of women during parturition, and complement C5b-9 complexes were deposited on fetal membranes.

  4. Compound 49b Prevents Diabetes-Induced Apoptosis through Increased IGFBP-3 Levels

    PubMed Central

    Zhang, Qiuhua; Guy, Kimberly; Pagadala, Jayaprakash; Jiang, Youde; Walker, Robert J; Liu, Luhong; Soderland, Carl; Kern, Timothy S; Ferry, Robert; He, Hui; Yates, C. Ryan; Miller, Duane D; Steinle, Jena J

    2012-01-01

    Purpose. To determine whether Compound 49b, a novel PKA-activating drug, can prevent diabetic-like changes in the rat retina through increased insulin-like growth factor binding protein-3 (IGFBP-3) levels. Methods. For the cell culture studies, we used both human retinal endothelial cells (REC) and retinal Müller cells in either 5 mM (normal) or 25 mM (high) glucose. Cells were treated with 50 nM Compound 49b alone of following treatment with protein kinase A (PKA) siRNA or IGFBP-3 siRNA. Western blotting and ELISA analyses were done to verify PKA and IGFBP-3 knockdown, as well as to measure apoptotic markers. For animal studies, we used streptozotocin-treated rats after 2 and 8 months of diabetes. Some rats were treated topically with 1 mM Compound 49b. Analyses were done for retinal thickness, cell numbers in the ganglion cell layer, pericyte ghosts, and numbers of degenerate capillaries, as well as electroretinogram and heart morphology. Results. Compound 49b requires active PKA and IGFBP-3 to prevent apoptosis of REC. Compound 49b significantly reduced the numbers of degenerate capillaries and pericyte ghosts, while preventing the decreased retinal thickness and loss of cells in the ganglion cell layer. Compound 49b maintained a normal electroretinogram, with no changes in blood pressure, intraocular pressure, or heart morphological changes. Conclusions. Topical Compound 49b is able to prevent diabetic-like changes in the rat retina, without producing systemic changes. Compound 49b is able to prevent REC apoptosis through increasing IGFBP-3 levels, which are reduced in response to hyperglycemia. PMID:22467575

  5. Cofilin/Twinstar Phosphorylation Levels Increase in Response to Impaired Coenzyme A Metabolism

    PubMed Central

    Siudeja, Katarzyna; Grzeschik, Nicola A.; Rana, Anil; de Jong, Jannie; Sibon, Ody C. M.

    2012-01-01

    Coenzyme A (CoA) is a pantothenic acid-derived metabolite essential for many fundamental cellular processes including energy, lipid and amino acid metabolism. Pantothenate kinase (PANK), which catalyses the first step in the conversion of pantothenic acid to CoA, has been associated with a rare neurodegenerative disorder PKAN. However, the consequences of impaired PANK activity are poorly understood. Here we use Drosophila and human neuronal cell cultures to show how PANK deficiency leads to abnormalities in F-actin organization. Cells with reduced PANK activity are characterized by abnormally high levels of phosphorylated cofilin, a conserved actin filament severing protein. The increased levels of phospho-cofilin coincide with morphological changes of PANK-deficient Drosophila S2 cells and human neuronal SHSY-5Y cells. The latter exhibit also markedly reduced ability to form neurites in culture – a process that is strongly dependent on actin remodeling. Our results reveal a novel and conserved link between a metabolic biosynthesis pathway, and regulation of cellular actin dynamics. PMID:22912811

  6. Mitohormesis: Promoting Health and Lifespan by Increased Levels of Reactive Oxygen Species (ROS)

    PubMed Central

    Ristow, Michael; Schmeisser, Kathrin

    2014-01-01

    Increasing evidence indicates that reactive oxygen species (ROS), consisting of superoxide, hydrogen peroxide, and multiple others, do not only cause oxidative stress, but rather may function as signaling molecules that promote health by preventing or delaying a number of chronic diseases, and ultimately extend lifespan. While high levels of ROS are generally accepted to cause cellular damage and to promote aging, low levels of these may rather improve systemic defense mechanisms by inducing an adaptive response. This concept has been named mitochondrial hormesis or mitohormesis. We here evaluate and summarize more than 500 publications from current literature regarding such ROS-mediated low-dose signaling events, including calorie restriction, hypoxia, temperature stress, and physical activity, as well as signaling events downstream of insulin/IGF-1 receptors, AMP-dependent kinase (AMPK), target-of-rapamycin (TOR), and lastly sirtuins to culminate in control of proteostasis, unfolded protein response (UPR), stem cell maintenance and stress resistance. Additionally, consequences of interfering with such ROS signals by pharmacological or natural compounds are being discussed, concluding that particularly antioxidants are useless or even harmful. PMID:24910588

  7. Enhanced zinc consumption causes memory deficits and increased brain levels of zinc

    USGS Publications Warehouse

    Flinn, J.M.; Hunter, D.; Linkous, D.H.; Lanzirotti, A.; Smith, L.N.; Brightwell, J.; Jones, B.F.

    2005-01-01

    Zinc deficiency has been shown to impair cognitive functioning, but little work has been done on the effects of elevated zinc. This research examined the effect on memory of raising Sprague-Dawley rats on enhanced levels of zinc (10 ppm ZnCO3; 0.153 mM) in the drinking water for periods of 3 or 9 months, both pre- and postnatally. Controls were raised on lab water. Memory was tested in a series of Morris Water Maze (MWM) experiments, and zinc-treated rats were found to have impairments in both reference and working memory. They were significantly slower to find a stationary platform and showed greater thigmotaxicity, a measure of anxiety. On a working memory task, where the platform was moved each day, zinc-treated animals had longer latencies over both trials and days, swam further from the platform, and showed greater thigmotaxicity. On trials using an Atlantis platform, which remained in one place but was lowered on probe trials, the zinc-treated animals had significantly fewer platform crossings, spent less time in the target quadrant, and did not swim as close to the platform position. They had significantly greater latency on nonprobe trials. Microprobe synchrotron X-ray fluorescence (??SXRF) confirmed that brain zinc levels were increased by adding ZnCO 3 to the drinking water. These data show that long-term dietary administration of zinc can lead to impairments in cognitive function. ?? 2004 Elsevier Inc. All rights reserved.

  8. Are symptoms associated with increased levels of perceived stress in first-episode psychosis?

    PubMed

    Renwick, Laoise; Jackson, Deirdre; Turner, Niall; Sutton, Marie; Foley, Sharon; McWilliams, Stephen; Kinsella, Anthony; O'Callaghan, Eadbhard

    2009-06-01

    Several studies report on the presence of external stress and life events prior to the onset and exacerbation of psychotic illness. However, the relationship between the subjective appraisal of stress at first presentation with psychosis is less well understood. This paper reports on the relationship between the individual perception of stress and symptomatology in individuals with first-episode psychosis at presentation to community mental health services. We assessed 123 individuals using standardized measures of symptoms, quality of life, perceived stress, global functioning, and duration of untreated psychosis. At first presentation, people with more depressive symptoms and reduced overall functioning were more likely to report increased levels of perceived stress. In addition, people with less positive symptoms of psychosis were experiencing higher levels of subjective stress. In terms of stress vulnerability models, it is important to consider how functioning and symptoms can influence individual appraisal of stress. Acknowledging this interaction can provide opportunities for nursing interventions directed at enhancing adaptive coping and provide benchmarks for assessing the effectiveness of nursing interventions provided in the acute phase of psychosis. Further research should focus on the interaction between symptoms and individually-appraised stress over time.

  9. Increased Umbilical Cord PAI-1 Levels in Placental Insufficiency Are Associated with Fetal Hypoxia and Angiogenesis

    PubMed Central

    Seferovic, Maxim D.; Gupta, Madhulika B.

    2016-01-01

    In intrauterine growth restriction (IUGR), a subset of pregnancies undergoes placental vascular dysregulation resulting in restricted blood flow and fetal hypoxemia. Altered transcription of hypoxic regulated plasminogen activator inhibitor 1 (PAI-1) has been associated with pregnancy complications and angiogenic regulation. Here we assessed circulating PAI-1 as an indicator of placental insufficiency. Venous umbilical PAI-1 of hypoxemic (VpO2 20 versus 35 mmHg, p < 0.0001) placental insufficient pregnancies (resistance index 0.9 versus 0.63, p < 0.05) (n = 18) was compared to controls (n = 12). PAI-1 was increased (~10-fold, p < 0.001) and had a positive predictive ratio of 6.7. Further, PAI-1 levels correlated to blood oxygen (r = −0.68, p < 0.0001). The plasma's angiogenic potency measured in vitro was associated with umbilical cord blood PAI-1 levels (r = 0.65, p < 0.01). This association was attenuated by PAI-1 inhibiting antibody (p < 0.001). The results demonstrate PAI-1 as a potential marker of placental insufficiency and identify its close association with pathological hypoxia and angiogenesis in a subset of growth restricted pregnancies. PMID:26903689

  10. Smelling lavender and rosemary increases free radical scavenging activity and decreases cortisol level in saliva.

    PubMed

    Atsumi, Toshiko; Tonosaki, Keiichi

    2007-02-28

    Free radicals/reactive oxygen species are related to many biological phenomena such as inflammation, aging, and carcinogenesis. The body possesses various antioxidative systems (free radical scavenging activity, FRSA) for preventing oxidative stress, and saliva contains such activity. In the present study, we measured the total salivary FRSA induced after the smelling of lavender and rosemary essential oils that are widely used in aromatherapy. Various physiologically active substances in saliva such as cortisol, secretory IgA, and alpha-amylase activity were found to be correlated with aroma-induced FRSA. The subjects (22 healthy volunteers) sniffed aroma for 5 min, and each subject's saliva was collected immediately. FRSA was measured using 1,1-diphenyl-2-picrylhydrazyl. The FRSA values were increased by stimulation with low concentrations (1000 times dilution) of lavender or by high-concentrations (10 times dilution) of rosemary. In contrast, both lavender and rosemary stimulations decreased cortisol levels. A significant inverse correlation was observed between the FRSA values and the cortisol levels with each concentration of rosemary stimulation. No significant changes were noted in sIgA or alpha-amylase. These findings clarify that lavender and rosemary enhance FRSA and decrease the stress hormone, cortisol, which protects the body from oxidative stress. PMID:17291597

  11. Effect of increasing the level of omega-3 fatty acids on rat skeletal muscle sarcoplasmic reticulum.

    PubMed

    Stubbs, C D; Kisielewski, A E

    1990-09-01

    The effect of dietary supplementation with fish oil as compared to corn oil on the lipid dynamics and calcium ATPase activity of rat skeletal sarcoplasmic reticulum was examined. After four-week supplementation with fish oil, the levels of eicosapentaenoic (20:5 omega 3), docosapentaenoic (22:5 omega 3) and docosahexaenoic (22:6 omega 3) acids in the total lipids were 5.3, 5.5 and 28.1% of the total fatty acids, respectively. In contrast, with corn oil only 22:6 was found (8.9%). The level of these fatty acids in phosphatidylethanolamine from the membranes of animals fed fish oil was 4.2 (20:5), 5.4 (22:5) and 49.1% (22:6); and for phosphatidylcholine it was 5.4 (20:5), 4.6 (22:5) and 17.4% (22:6). Again, in corn oil fed animals, only 22:6 was found in appreciable amounts, namely 28.3% in phosphatidylethanolamine and 1.8% in phosphatidylcholine. The steady state fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene (DPH) was used to assess lipid order and was found to be only slightly less for membranes from animals supplemented with fish oil (0.120) as compared to those supplemented with corn oil (0.124). The calcium ATPase was found to be unaffected by supplementation consistent with the observed modest changes in lipid order as well as with suggestions that the enzyme is relatively insensitive to the level of unsaturation. It could be argued that if large increases in fatty acyl polyunsaturation in mammalian cell membranes would lead to marked alterations in bulk membrane lipid motional properties, this may not be in the interest of preserving physiological function.(ABSTRACT TRUNCATED AT 250 WORDS)

  12. Controlled sparse and percolating cross-linking in waterborne soft adhesives.

    PubMed

    Deplace, F; Carelli, C; Langenfeld, A; Rabjohns, M A; Foster, A B; Lovell, P A; Creton, C

    2009-09-01

    The effect of low levels of cross-linking on the adhesive and mechanical properties of waterborne pressure-sensitive adhesives was investigated. We have taken advantage of a core-shell latex particle morphology obtained by emulsion polymerization to create a heterogeneous structure of cross-links without major modification of the monomer composition. The latex particles comprise a shell containing cross-linkable diacetone acrylamide (DAAM) repeat units localized on the periphery of a slightly softer core copolymer of very similar composition. Adipic acid dihydrazide was added to the latex prior to film formation to react with DAAM repeat units and affect interfacial cross-linking between particles in the adhesive films. The honeycomb-like structure obtained after drying of the latex results in a good balance between the dissipative properties required for adhesion and the resistance to creep. The characterization of the mechanical properties of the films shows that the chosen cross-linking method creates a percolating lightly cross-linked network, swollen with a nearly un-cross-linked component. With this cross-linking method, the linear viscoelastic properties of the soft films are nearly unaffected by the cross-linking while the nonlinear tensile properties are greatly modified. As a result, the long-term shear resistance of the adhesive film improves very significantly while the peel force remains nearly the same. A simple rheological model is used to interpret qualitatively the changes in the material parameters induced by cross-linking. PMID:20355828

  13. Rice Bran Amendment Suppresses Potato Common Scab by Increasing Antagonistic Bacterial Community Levels in the Rhizosphere.

    PubMed

    Tomihama, Tsuyoshi; Nishi, Yatsuka; Mori, Kiyofumi; Shirao, Tsukasa; Iida, Toshiya; Uzuhashi, Shihomi; Ohkuma, Moriya; Ikeda, Seishi

    2016-07-01

    Potato common scab (PCS), caused by pathogenic Streptomyces spp., is a serious disease in potato production worldwide. Cultural practices, such as optimizing the soil pH and irrigation, are recommended but it is often difficult to establish stable disease reductions using these methods. Traditionally, local farmers in southwest Japan have amended soils with rice bran (RB) to suppress PCS. However, the scientific mechanism underlying disease suppression by RB has not been elucidated. The present study showed that RB amendment reduced PCS by repressing the pathogenic Streptomyces population in young tubers. Amplicon sequencing analyses of 16S ribosomal RNA genes from the rhizosphere microbiome revealed that RB amendment dramatically changed bacterial composition and led to an increase in the relative abundance of gram-positive bacteria such as Streptomyces spp., and this was negatively correlated with PCS disease severity. Most actinomycete isolates derived from the RB-amended soil showed antagonistic activity against pathogenic Streptomyces scabiei and S. turgidiscabies on R2A medium. Some of the Streptomyces isolates suppressed PCS when they were inoculated onto potato plants in a field experiment. These results suggest that RB amendment increases the levels of antagonistic bacteria against PCS pathogens in the potato rhizosphere.

  14. Combined atmospheric oxidant capacity and increased levels of exhaled nitric oxide

    NASA Astrophysics Data System (ADS)

    Yang, Changyuan; Li, Huichu; Chen, Renjie; Xu, Wenxi; Wang, Cuicui; Tse, Lap Ah; Zhao, Zhuohui; Kan, Haidong

    2016-07-01

    Nitrogen dioxide and ozone are two interrelated oxidative pollutants in the atmosphere. Few studies have evaluated the health effects of combined oxidant capacity (O x ). We investigated the short-term effects of O x on fractional exhaled nitric oxide (FeNO), a well-established biomarker for airway inflammation, in a group of chronic obstructive pulmonary disease patients. Real-time concentrations of O x were obtained by calculating directly the sum of nitrogen dioxide and ozone. Linear mixed-effect models were applied to explore the acute effects of O x on FeNO levels. Short-term exposure to Ox was significantly associated with elevated FeNO. This effect was strongest in the first 24 h after exposure, and was robust to the adjustment of PM2.5. A 10 μg m-3 increase in 24 h average concentrations of O x was associated with 4.28% (95% confidence interval: 1.19%, 7.37%) increase in FeNO. The effect estimates were statistically significant only among males, elders, and those with body mass index ≥24 kg m-2, a comorbidity, higher educational attainment, or moderate airflow limitation. This analysis demonstrated an independent effect of O x on respiratory inflammation, and suggested that a single metric O x might serve as a preferable indicator of atmospheric oxidative capacity in further air pollution epidemiological studies.

  15. Combined atmospheric oxidant capacity and increased levels of exhaled nitric oxide

    NASA Astrophysics Data System (ADS)

    Yang, Changyuan; Li, Huichu; Chen, Renjie; Xu, Wenxi; Wang, Cuicui; Tse, Lap Ah; Zhao, Zhuohui; Kan, Haidong

    2016-07-01

    Nitrogen dioxide and ozone are two interrelated oxidative pollutants in the atmosphere. Few studies have evaluated the health effects of combined oxidant capacity (O x ). We investigated the short-term effects of O x on fractional exhaled nitric oxide (FeNO), a well-established biomarker for airway inflammation, in a group of chronic obstructive pulmonary disease patients. Real-time concentrations of O x were obtained by calculating directly the sum of nitrogen dioxide and ozone. Linear mixed-effect models were applied to explore the acute effects of O x on FeNO levels. Short-term exposure to Ox was significantly associated with elevated FeNO. This effect was strongest in the first 24 h after exposure, and was robust to the adjustment of PM2.5. A 10 μg m‑3 increase in 24 h average concentrations of O x was associated with 4.28% (95% confidence interval: 1.19%, 7.37%) increase in FeNO. The effect estimates were statistically significant only among males, elders, and those with body mass index ≥24 kg m‑2, a comorbidity, higher educational attainment, or moderate airflow limitation. This analysis demonstrated an independent effect of O x on respiratory inflammation, and suggested that a single metric O x might serve as a preferable indicator of atmospheric oxidative capacity in further air pollution epidemiological studies.

  16. Effects of increased von Willebrand factor levels on primary hemostasis in thrombocytopenic patients with liver cirrhosis.

    PubMed

    Wannhoff, Andreas; Müller, Oliver J; Friedrich, Kilian; Rupp, Christian; Klöters-Plachky, Petra; Leopold, Yvonne; Brune, Maik; Senner, Mirja; Weiss, Karl-Heinz; Stremmel, Wolfgang; Schemmer, Peter; Katus, Hugo A; Gotthardt, Daniel N

    2014-01-01

    In patients with liver cirrhosis procoagulant and anticoagulant changes occur simultaneously. During primary hemostasis, platelets adhere to subendothelial structures, via von Willebrand factor (vWF). We aimed to investigate the influence of vWF on primary hemostasis in patients with liver cirrhosis. Therefore we assessed in-vitro bleeding time as marker of primary hemostasis in cirrhotic patients, measuring the Platelet Function Analyzer (PFA-100) closure times with collagen and epinephrine (Col-Epi, upper limit of normal ≤ 165 s) or collagen and ADP (Col-ADP, upper limit of normal ≤ 118 s). If Col-Epi and Col-ADP were prolonged, the PFA-100 was considered to be pathological. Effects of vWF on primary hemostasis in thrombocytopenic patients were analyzed and plasma vWF levels were modified by adding recombinant vWF or anti-vWF antibody. Of the 72 included cirrhotic patients, 32 (44.4%) showed a pathological result for the PFA-100. They had mean closure times (± SD) of 180 ± 62 s with Col-Epi and 160 ± 70 s with Col-ADP. Multivariate analysis revealed that hematocrit (P = 0.027) and vWF-antigen levels (P = 0.010) are the predictors of a pathological PFA-100 test in cirrhotic patients. In 21.4% of cirrhotic patients with platelet count ≥ 150/nL and hematocrit ≥ 27.0%, pathological PFA-100 results were found. In thrombocytopenic (< 150/nL) patients with cirrhosis, normal PFA-100 results were associated with higher vWF-antigen levels (462.3 ± 235.9% vs. 338.7 ± 151.6%, P = 0.021). These results were confirmed by multivariate analysis in these patients as well as by adding recombinant vWF or polyclonal anti-vWF antibody that significantly shortened or prolonged closure times, respectively. In conclusion, primary hemostasis is impaired in cirrhotic patients. The effect of reduced platelet count in cirrhotic patients can at least be partly compensated by increased vWF levels. Recombinant vWF could be an alternative to platelet transfusions in the future.

  17. Actin Cross-Linkers and the Shape of Stereocilia

    PubMed Central

    Lenz, Martin; Prost, Jacques; Joanny, Jean-François

    2010-01-01

    Stereocilia are actin-based cellular protrusions essential for hearing. We propose that they are shaped by the detachment dynamics of actin cross-linkers, in particular espin. We account for experimentally observed stereocilium shapes, treadmilling velocity to length relationship, espin 1 localization profile, and microvillus length to espin level relationship. If the cross-linkers are allowed to reattach, our model yields a dynamical phase transition toward unbounded growth. Considering the simplified case of a noninteracting, one-filament system, we calculate the length probability distribution in the growing phase and its stationary form in a continuum approximation of the finite-length phase. Numerical simulations of interacting filaments suggest an anomalous power-law divergence of the protrusion length at the growth transition, which could be a universal feature of cross-linked depolymerizing systems. PMID:20959082

  18. Friedel–Crafts Crosslinked Highly Sulfonated Polyether Ether Ketone (SPEEK) Membranes for a Vanadium/Air Redox Flow Battery

    PubMed Central

    Merle, Géraldine; Ioana, Filipoi Carmen; Demco, Dan Eugen; Saakes, Michel; Hosseiny, Seyed Schwan

    2014-01-01

    Highly conductive and low vanadium permeable crosslinked sulfonated poly(ether ether ketone) (cSPEEK) membranes were prepared by electrophilic aromatic substitution for a Vanadium/Air Redox Flow Battery (Vanadium/Air-RFB) application. Membranes were synthesized from ethanol solution and crosslinked under different temperatures with 1,4-benzenedimethanol and ZnCl2 via the Friedel–Crafts crosslinking route. The crosslinking mechanism under different temperatures indicated two crosslinking pathways: (a) crosslinking on the sulfonic acid groups; and (b) crosslinking on the backbone. It was observed that membranes crosslinked at a temperature of 150 °C lead to low proton conductive membranes, whereas an increase in crosslinking temperature and time would lead to high proton conductive membranes. High temperature crosslinking also resulted in an increase in anisotropy and water diffusion. Furthermore, the membranes were investigated for a Vanadium/Air Redox Flow Battery application. Membranes crosslinked at 200 °C for 30 min with a molar ratio between 2:1 (mol repeat unit:mol benzenedimethanol) showed a proton conductivity of 27.9 mS/cm and a 100 times lower VO2+ crossover compared to Nafion. PMID:24957118

  19. Friedel-Crafts Crosslinked Highly Sulfonated Polyether Ether Ketone (SPEEK) Membranes for a Vanadium/Air Redox Flow Battery.

    PubMed

    Merle, Géraldine; Ioana, Filipoi Carmen; Demco, Dan Eugen; Saakes, Michel; Hosseiny, Seyed Schwan

    2013-12-30

    Highly conductive and low vanadium permeable crosslinked sulfonated poly(ether ether ketone) (cSPEEK) membranes were prepared by electrophilic aromatic substitution for a Vanadium/Air Redox Flow Battery (Vanadium/Air-RFB) application. Membranes were synthesized from ethanol solution and crosslinked under different temperatures with 1,4-benzenedimethanol and ZnCl2 via the Friedel-Crafts crosslinking route. The crosslinking mechanism under different temperatures indicated two crosslinking pathways: (a) crosslinking on the sulfonic acid groups; and (b) crosslinking on the backbone. It was observed that membranes crosslinked at a temperature of 150 °C lead to low proton conductive membranes, whereas an increase in crosslinking temperature and time would lead to high proton conductive membranes. High temperature crosslinking also resulted in an increase in anisotropy and water diffusion. Furthermore, the membranes were investigated for a Vanadium/Air Redox Flow Battery application. Membranes crosslinked at 200 °C for 30 min with a molar ratio between 2:1 (mol repeat unit:mol benzenedimethanol) showed a proton conductivity of 27.9 mS/cm and a 100 times lower VO2+ crossover compared to Nafion.

  20. Effects of Crosslinking on the Mechanical Properties Drug Release, and Cytocompatibility of Protein Polymers

    PubMed Central

    Martinez, Adam W.; Caves, Jeffrey M.; Ravi, Swathi; Li, Wehnsheng; Chaikof, Elliot L.

    2013-01-01

    Recombinant elastin-like protein polymers are increasingly being investigated as component materials of a variety of implantable medical devices. This is chiefly a result of their favorable biological properties and the ability to tailor their physical and mechanical properties. In this report, we explore the potential of modulating the water content, mechanical properties, and drug release profiles of protein films through the selection of different crosslinking schemes and processing strategies. We find that the selection of crosslinking scheme and processing strategy has a significant influence on all aspects of protein polymer films. Significantly, utilization of a confined, fixed volume, as well as vapor phase crosslinking strategies decreased protein polymer equilibrium water content. Specifically, as compared to uncrosslinked protein gels, water content was reduced for genipin (15.5%), glutaraldehyde (GTA) (24.5%), GTA vapor crosslinking (31.6%), disulfide (SS) (18.2%), and SS vapor crosslinking (25.5%) (p <0.05). Distinct crosslinking strategies modulated protein polymer stiffness, strain at failure, and ultimate tensile strength (UTS). In all cases, vapor phase crosslinking produced the stiffest films with the highest UTS. Moreover, both confined, fixed volume and vapor phase approaches influenced drug delivery rates; with decreased initial drug burst and release rates as compared to solution phase crosslinking. Tailored crosslinking strategies provide an important option for modulating the physical, mechanical, and drug delivery properties of protein polymers. PMID:23993944

  1. Effect of sterilization and crosslinking on gelatin films.

    PubMed

    Amadori, Sofia; Torricelli, Paola; Rubini, Katia; Fini, Milena; Panzavolta, Silvia; Bigi, Adriana

    2015-02-01

    Sterilization through γ-irradiation has been reported to affect collagen mechanical properties, but its possible effects on gelatin based materials have not been investigated up to now. Herein we report the results of a mechanical, chemical and thermal study performed on gelatin films before and after γ-irradiation. The investigation was performed on uncrosslinked films as well as on crosslinked films. To this aim, two common crosslinking agents, glutaraldehyde and genipin, at different concentration (0.15, 0.30 and 0.67%) were used. The results indicate that sterilization significantly affects the mechanical properties of uncrosslinked films, whereas it displays a modest effect on gelatin swelling, release in solution, thermal stability and molecular structure. Both glutaraldehyde and genipin enhance the mechanical properties and stability in solution of the gelatin films. In particular, the values of Young modulus increase as a function of crosslinker concentration up to about 10 and 18 MPa for genipin and glutaraldehyde treated samples respectively. The results of in vitro study demonstrate that the films crosslinked with genipin do not display any cytotoxic reaction, whereas glutaraldehyde crosslinking provokes an acute and dose dependent cytotoxic effect.

  2. Reduced antioxidant level and increased oxidative damage in intact liver lobes during ischaemia-reperfusion

    PubMed Central

    Váli, László; Taba, Gabriella; Szentmihályi, Klára; Fébel, Hedvig; Kurucz, Tímea; Pallai, Zsolt; Kupcsulik, Péter; Blázovics, Anna

    2006-01-01

    AIM: To determine whether increased blood flow of the liver can cause oxidative stress and hepatocyte damage, and to elaborate methods suitable for measuring the antioxidant defence during hepatic surgery on rat model. METHODS: In nembutal narcosis, the left lateral and the medial lobes of the liver were clipped for 45 min to make the total blood supply flow through the other lobes. Total antioxidant status, glutathione peroxidase and superoxide dysmutase activity, as well as the concentrations of diene conjugates and free sulphydril groups, H-donating ability and reducing power of the liver samples were determined. Chemiluminescent intensity of the liver was also measured. Metal ions (Al, Ca, Cu, Fe, Mg, Mn, Zn) and P and S concentrations of the liver were determined with an inductively coupled plasma optical emission spectrometer and Se content was measured by cathodic stripping voltammetry. RESULTS: Glutathione peroxidase and superoxide dysmutase activities of the liver decreased significantly in the hyperemia group compared to those observed in the sham operated group. The level of total antioxidant status was also significantly lower in the hyperemia group. H-donating ability, reducing power and free sulphydril group concentration showed the same tendency. A significant correlation (P<0.05) was found between the changes in non-specific antioxidant activities. This pointed to simultaneous activity of the antioxidant defence system. Al, Cu, Mn, Zn, and S were lower in the hyperemia group than in the sham operated group when the levels of Ca, Fe, Mg, Se and P ions were higher during hyperemia. CONCLUSION: Oxidative stress is one of the main factors for the injury of intact liver lobes during ischaemia-reperfusion. PMID:16534850

  3. DNA Methylation is Associated with an Increased Level of Conservation at Nondegenerate Nucleotides in Mammals

    PubMed Central

    Chuang, Trees-Juen; Chen, Feng-Chi

    2014-01-01

    DNA methylation at CpG dinucleotides can significantly increase the rate of cytosine-to-thymine mutations and the level of sequence divergence. Although the correlations between DNA methylation and genomic sequence evolution have been widely studied, an unaddressed yet fundamental question is how DNA methylation is associated with the conservation of individual nucleotides in different sequence contexts. Here, we demonstrate that in mammalian exons, the correlations between DNA methylation and the conservation of individual nucleotides are dependent on the type of exonic sequence (coding or untranslated), the degeneracy of coding nucleotides, background selection pressure, and the relative position (first or nonfirst exon in the transcript) where the nucleotides are located. For untranslated and nonzero-fold degenerate nucleotides, methylated sites are less conserved than unmethylated sites regardless of background selection pressure and the relative position of the exon. For zero-fold degenerate (or nondegenerate) nucleotides, however, the reverse trend is observed in nonfirst coding exons and first coding exons that are under stringent background selection pressure. Furthermore, cytosine-to-thymine mutations at methylated zero-fold degenerate nucleotides are predicted to be more detrimental than those that occur at unmethylated nucleotides. As zero-fold and nonzero-fold degenerate nucleotides are very close to each other, our results suggest that the “functional resolution” of DNA methylation may be finer than previously recognized. In addition, the positive correlation between CpG methylation and the level of conservation at zero-fold degenerate nucleotides implies that CpG methylation may serve as an “indicator” of functional importance of these nucleotides. PMID:24157417

  4. Computational Analysis of Viscoelastic Properties of Crosslinked Actin Networks

    PubMed Central

    Kim, Taeyoon; Hwang, Wonmuk; Lee, Hyungsuk; Kamm, Roger D.

    2009-01-01

    Mechanical force plays an important role in the physiology of eukaryotic cells whose dominant structural constituent is the actin cytoskeleton composed mainly of actin and actin crosslinking proteins (ACPs). Thus, knowledge of rheological properties of actin networks is crucial for understanding the mechanics and processes of cells. We used Brownian dynamics simulations to study the viscoelasticity of crosslinked actin networks. Two methods were employed, bulk rheology and segment-tracking rheology, where the former measures the stress in response to an applied shear strain, and the latter analyzes thermal fluctuations of individual actin segments of the network. It was demonstrated that the storage shear modulus (G′) increases more by the addition of ACPs that form orthogonal crosslinks than by those that form parallel bundles. In networks with orthogonal crosslinks, as crosslink density increases, the power law exponent of G′ as a function of the oscillation frequency decreases from 0.75, which reflects the transverse thermal motion of actin filaments, to near zero at low frequency. Under increasing prestrain, the network becomes more elastic, and three regimes of behavior are observed, each dominated by different mechanisms: bending of actin filaments, bending of ACPs, and at the highest prestrain tested (55%), stretching of actin filaments and ACPs. In the last case, only a small portion of actin filaments connected via highly stressed ACPs support the strain. We thus introduce the concept of a ‘supportive framework,’ as a subset of the full network, which is responsible for high elasticity. Notably, entropic effects due to thermal fluctuations appear to be important only at relatively low prestrains and when the average crosslinking distance is comparable to or greater than the persistence length of the filament. Taken together, our results suggest that viscoelasticity of the actin network is attributable to different mechanisms depending on the amount

  5. Computational analysis of viscoelastic properties of crosslinked actin networks.

    PubMed

    Kim, Taeyoon; Hwang, Wonmuk; Lee, Hyungsuk; Kamm, Roger D

    2009-07-01

    Mechanical force plays an important role in the physiology of eukaryotic cells whose dominant structural constituent is the actin cytoskeleton composed mainly of actin and actin crosslinking proteins (ACPs). Thus, knowledge of rheological properties of actin networks is crucial for understanding the mechanics and processes of cells. We used Brownian dynamics simulations to study the viscoelasticity of crosslinked actin networks. Two methods were employed, bulk rheology and segment-tracking rheology, where the former measures the stress in response to an applied shear strain, and the latter analyzes thermal fluctuations of individual actin segments of the network. It was demonstrated that the storage shear modulus (G') increases more by the addition of ACPs that form orthogonal crosslinks than by those that form parallel bundles. In networks with orthogonal crosslinks, as crosslink density increases, the power law exponent of G' as a function of the oscillation frequency decreases from 0.75, which reflects the transverse thermal motion of actin filaments, to near zero at low frequency. Under increasing prestrain, the network becomes more elastic, and three regimes of behavior are observed, each dominated by different mechanisms: bending of actin filaments, bending of ACPs, and at the highest prestrain tested (55%), stretching of actin filaments and ACPs. In the last case, only a small portion of actin filaments connected via highly stressed ACPs support the strain. We thus introduce the concept of a 'supportive framework,' as a subset of the full network, which is responsible for high elasticity. Notably, entropic effects due to thermal fluctuations appear to be important only at relatively low prestrains and when the average crosslinking distance is comparable to or greater than the persistence length of the filament. Taken together, our results suggest that viscoelasticity of the actin network is attributable to different mechanisms depending on the amount of

  6. Adsorption of allura red dye by cross-linked chitosan from shrimp waste.

    PubMed

    Sánchez-Duarte, Reyna G; Sánchez-Machado, Dalia I; López-Cervantes, Jaime; Correa-Murrieta, Ma A

    2012-01-01

    The present study was designed to evaluate the chitosan, which has been obtained by deacetylation of chitin, as a biosorbent. The chitin was isolated from fermented shrimp waste by an important local industrial food biopolymer. The aim of this work was the characterization of chitosan and preparation of cross-linked chitosan- tripolyphosphate (chitosan-TPP) beads for the removal of allura red food dye from aqueous solutions. Conditions of batch adsorption such as pH, time and adsorbent dose were examined. The effectiveness of cross-linked chitosan beads for dye removal was found to be higher for pH 2 (98%, percentage of dye removal) and tends to decrease at pHs of 3 to 11 (up to 49%). The values of percentage removal show that the adsorption capacity increases with time of contact and dosage of chitosan-TPP, but red dye adsorption is mainly influenced by pH level. The cross-linked chitosan-TPP beads can significantly adsorb allura red monoazo dye from aqueous solutions even at acidic pHs unlike raw chitosan beads that tend to dissolve in acidic solutions. Consequently, this modified chitosan has characteristics that allow minimization of environmental pollution and widening the valorization of shrimp waste.

  7. Intermediate closed state for glycine receptor function revealed by cysteine cross-linking

    PubMed Central

    Prevost, Marie S.; Moraga-Cid, Gustavo; Van Renterghem, Catherine; Edelstein, Stuart J.; Changeux, Jean-Pierre; Corringer, Pierre-Jean

    2013-01-01

    Pentameric ligand-gated ion channels (pLGICs) mediate signal transmission by coupling the binding of extracellular ligands to the opening of their ion channel. Agonist binding elicits activation and desensitization of pLGICs, through several conformational states, that are, thus far, incompletely characterized at the structural level. We previously reported for GLIC, a prokaryotic pLGIC, that cross-linking of a pair of cysteines at both sides of the extracellular and transmembrane domain interface stabilizes a locally closed (LC) X-ray structure. Here, we introduced the homologous pair of cysteines on the human α1 glycine receptor. We show by electrophysiology that cysteine cross-linking produces a gain-of-function phenotype characterized by concomitant constitutive openings, increased agonist potency, and equalization of efficacies of full and partial agonists. However, it also produces a reduction of maximal currents at saturating agonist concentrations without change of the unitary channel conductance, an effect reversed by the positive allosteric modulator propofol. The cross-linking thus favors a unique closed state distinct from the resting and longest-lived desensitized states. Fitting the data according to a three-state allosteric model suggests that it could correspond to a LC conformation. Its plausible assignment to a gating intermediate or a fast-desensitized state is discussed. Overall, our data show that relative movement of two loops at the extracellular-transmembrane interface accompanies orthosteric agonist-mediated gating. PMID:24085847

  8. Declines in large wildlife increase landscape-level prevalence of rodent-borne disease in Africa.

    PubMed

    Young, Hillary S; Dirzo, Rodolfo; Helgen, Kristofer M; McCauley, Douglas J; Billeter, Sarah A; Kosoy, Michael Y; Osikowicz, Lynn M; Salkeld, Daniel J; Young, Truman P; Dittmar, Katharina

    2014-05-13

    Populations of large wildlife are declining on local and global scales. The impacts of this pulse of size-selective defaunation include cascading changes to smaller animals, particularly rodents, and alteration of many ecosystem processes and services, potentially involving changes to prevalence and transmission of zoonotic disease. Understanding linkages between biodiversity loss and zoonotic disease is important for both public health and nature conservation programs, and has been a source of much recent scientific debate. In the case of rodent-borne zoonoses, there is strong conceptual support, but limited empirical evidence, for the hypothesis that defaunation, the loss of large wildlife, increases zoonotic disease risk by directly or indirectly releasing controls on rodent density. We tested this hypothesis by experimentally excluding large wildlife from a savanna ecosystem in East Africa, and examining changes in prevalence and abundance of Bartonella spp. infection in rodents and their flea vectors. We found no effect of wildlife removal on per capita prevalence of Bartonella infection in either rodents or fleas. However, because rodent and, consequently, flea abundance doubled following experimental defaunation, the density of infected hosts and infected fleas was roughly twofold higher in sites where large wildlife was absent. Thus, defaunation represents an elevated risk in Bartonella transmission to humans (bartonellosis). Our results (i) provide experimental evidence of large wildlife defaunation increasing landscape-level disease prevalence, (ii) highlight the importance of susceptible host regulation pathways and host/vector density responses in biodiversity-disease relationships, and (iii) suggest that rodent-borne disease responses to large wildlife loss may represent an important context where this relationship is largely negative.

  9. Declines in large wildlife increase landscape-level prevalence of rodent-borne disease in Africa

    PubMed Central

    Young, Hillary S.; Dirzo, Rodolfo; Helgen, Kristofer M.; McCauley, Douglas J.; Kosoy, Michael Y.; Osikowicz, Lynn M.; Salkeld, Daniel J.; Young, Truman P.; Dittmar, Katharina

    2014-01-01

    Populations of large wildlife are declining on local and global scales. The impacts of this pulse of size-selective defaunation include cascading changes to smaller animals, particularly rodents, and alteration of many ecosystem processes and services, potentially involving changes to prevalence and transmission of zoonotic disease. Understanding linkages between biodiversity loss and zoonotic disease is important for both public health and nature conservation programs, and has been a source of much recent scientific debate. In the case of rodent-borne zoonoses, there is strong conceptual support, but limited empirical evidence, for the hypothesis that defaunation, the loss of large wildlife, increases zoonotic disease risk by directly or indirectly releasing controls on rodent density. We tested this hypothesis by experimentally excluding large wildlife from a savanna ecosystem in East Africa, and examining changes in prevalence and abundance of Bartonella spp. infection in rodents and their flea vectors. We found no effect of wildlife removal on per capita prevalence of Bartonella infection in either rodents or fleas. However, because rodent and, consequently, flea abundance doubled following experimental defaunation, the density of infected hosts and infected fleas was roughly twofold higher in sites where large wildlife was absent. Thus, defaunation represents an elevated risk in Bartonella transmission to humans (bartonellosis). Our results (i) provide experimental evidence of large wildlife defaunation increasing landscape-level disease prevalence, (ii) highlight the importance of susceptible host regulation pathways and host/vector density responses in biodiversity–disease relationships, and (iii) suggest that rodent-borne disease responses to large wildlife loss may represent an important context where this relationship is largely negative. PMID:24778215

  10. The carcinogen safrole increases intracellular free Ca2+ levels and causes death in MDCK cells.

    PubMed

    Chen, Wei-Chuan; Cheng, He-Hsiung; Huang, Chun-Jen; Lu, Yih-Chau; Chen, I-Shu; Liu, Shiuh-Inn; Hsu, Shu-Shong; Chang, Hong-Tai; Huang, Jong-Khing; Chen, Jin-Shyr; Jan, Chung-Ren

    2007-02-28

    The effect of the carcinogen safrole on intracellular Ca2+ movement in renal tubular cells has not been explored previously. The present study examined whether safrole could alter Ca2+ handling in Madin-Darby canine kidney (MDCK) cells. Cytosolic free Ca2+ levels ([Ca2+]i) in populations of cells were measured using fura-2 as a fluorescent Ca2+ probe. Safrole at concentrations above 33 microM increased [Ca2+]i in a concentration-dependent manner with an EC50 value of 400 microM. The Ca2+ signal was reduced by 90% by removing extracellular Ca2+, but was not affected by nifedipine, verapamil, or diltiazem. Addition of Ca2+ after safrole had depleted intracellular Ca(2+)-induced dramatic Ca2+ influx, suggesting that safrole caused store-operated Ca2+ entry. In Ca(2+)-free medium, after pretreatment with 650 microM safrole, 1 microM thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor) failed to release more Ca 2+. Inhibition of phospholipase C with 2 microM U73122 did not affect safrole-induced Ca2+ release. Trypan blue exclusion assays revealed that incubation with 650 microM safrole for 30 min did not kill cells, but killed 70% of cells after incubation for 60 min. Collectively, the data suggest that in MDCK cells, safrole induced a [Ca2+] increase by causing Ca2+ release from the endoplasmic reticulum in a phospholipase C-independent fashion, and by inducing Ca2+ influx via store-operated Ca2+ entry. Furthermore, safrole can cause acute toxicity to MDCK cells.

  11. Effect of increased methionine level on performance and apparent ileal digestibility of amino acids in ducks.

    PubMed

    Jamroz, D; Wiliczkiewicz, A; Lemme, A; Orda, J; Skorupińska, J; Wertelecki, T

    2009-10-01

    The experiment was conducted with 960 one-day-old ducklings fed mixtures (I control - 0.28% methionine) additionally supplemented with DL-methionine (DL-Met) at amounts: 0.03% (group II), 0.07% (III), 0.12% (IV) and 0.18% (V). The performance, carcass quality and apparent ileal digestibility of amino acids as the criterions of methionine (Met) effectivity were considered. The analysis of growth and development of ducks as an effect of diversified DL-Met supplements indicate that increased content of this amino acid in the diets has not affected clearly the performance parameters. The body weight of 21-day-old ducklings was significantly affected only by the level of 0.12% of added Met in comparison to control group. On day 42, the differences among groups were negligible; only the addition of 0.12% DL-Met has increased the body weight by 2.4% when compared with control (p > 0.05). Feed conversion estimated for a period of 1-42 days has not been influenced by Met supplementation. The indistinct, however, visible tendency of better ileal amino acids' apparent digestibility (for Asp.a.,Thr, Ser, Glu, Lys) was noted in the groups fed supplemented diets. Application of 0.07% and 0.18% of DL-met, has significantly (p < 0.05) improved the coefficient of cysteine (Cys) apparent ileal digestibility; however, the improvement of Met apparent ileal digestibility has been achieved by the addition of 0.18% Met. The mortality of ducklings in the experiment was very low and varied between 3.15% (II) and 0.0% (groups I and III). In general, application of 0.12% of DL-Met to mixture containing 0.28% Met had positive effect on the productive output of birds and also improved the apparent ileal digestibility of Cys and Met.

  12. Corneal collagen cross-linking: A review

    PubMed Central

    O’Brart, David P.S.

    2014-01-01

    The aim was to review the published literature on corneal collagen cross-linking. The emphasis was on the seminal publications, systemic reviews, meta-analyses and randomized controlled trials. Where such an evidence did not exist, selective large series cohort studies, case controlled studies and case series with follow-up preferably greater than 12 months were included. Riboflavin/Ultraviolet A (UVA) corneal collagen cross-linking appears to be the first treatment modality to halt the progression of keratoconus and other corneal ectatic disorders with improvement in visual, keratometric and topographic parameters documented by most investigators. Its precise mechanism of action at a molecular level is as yet not fully determined. Follow-up is limited to 4–6 years at present but suggests continued stability and improvement in corneal shape with time. Most published data are with epithelium-off techniques. Epithelium-on studies suggest some efficacy but less than with the epithelium-off procedures and long-term data are not currently available. The use of Riboflavin/UVA CXL for the management of infectious and non-infectious keratitis appears very promising. Its use in the management of bullous keratopathy is equivocal. Investigation of other methodologies for CXL are under investigation. PMID:25000866

  13. Extreme dryness and DNA-protein cross-links

    NASA Astrophysics Data System (ADS)

    Bieger-Dose, A.; Dose, K.; Meffert, R.; Mehler, M.; Risi, S.

    Exposure of fungal conidia (Aspergillus ochraceus) or spores of Bacillus subtilis to extreme dryness or vacuum induces DNA lesions, including strand breaks and the formation of DNA-protein cross-links. In wet cells only a small amount of protein is bound to DNA, but exposure to conditions of lowered water activity results in an increasing number of cross-links between DNA and proteins. In fungal conidia these cross-links are detected after selective iodination (125J) of the DNA-bound proteins followed by gel electrophoresis and subsequent autoradiography. Another approach is the labelling of DNA with 32p by means of nick translation and the detection of differences in the electrophoretic mobility of DNA before and after digestion with proteinase K of proteins bound to DNA.

  14. Memory deficit associated with increased brain proinflammatory cytokine levels and neurodegeneration in acute ischemic stroke.

    PubMed

    Silva, Bruno; Sousa, Larissa; Miranda, Aline; Vasconcelos, Anilton; Reis, Helton; Barcelos, Lucíola; Arantes, Rosa; Teixeira, Antonio; Rachid, Milene Alvarenga

    2015-08-01

    The present study aimed to investigate behavioral changes and neuroinflammatory process following left unilateral common carotid artery occlusion (UCCAO), a model of cerebral ischemia. Post-ischemic behavioral changes following 15 min UCCAO were recorded 24 hours after reperfusion. The novel object recognition task was used to assess learning and memory. After behavioral test, brains from sham and ischemic mice were removed and processed to evaluate central nervous system pathology by TTC and H&E techniques as well as inflammatory mediators by ELISA. UCCAO promoted long-term memory impairment after reperfusion. Infarct areas were observed in the cerebrum by TTC stain. Moreover, the histopathological analysis revealed cerebral necrotic cavities surrounded by ischemic neurons and hippocampal neurodegeneration. In parallel with memory dysfunction, brain levels of TNF-a, IL-1b and CXCL1 were increased post ischemia compared with sham-operated group. These findings suggest an involvement of central nervous system inflammatory mediators and brain damage in cognitive impairment following unilateral acute ischemia.

  15. Assessing the sensitivity of human skin hyperspectral responses to increasing anemia severity levels

    NASA Astrophysics Data System (ADS)

    Baranoski, Gladimir V. G.; Dey, Ankita; Chen, Tenn F.

    2015-09-01

    Anemia is a prevalent medical condition that seriously affects millions of people all over the world. In many regions, not only its initial detection but also its monitoring are hindered by limited access to laboratory facilities. This situation has motivated the development of a wide range of optical devices and procedures to assist physicians in these tasks. Although noticeable progress has been achieved in this area, the search for reliable, low-cost, and risk-free solutions still continues, and the strengthening of the knowledge base about this disorder and its effects is essential for the success of these initiatives. We contribute to these efforts by closely examining the sensitivity of human skin hyperspectral responses (within and outside the visible region of the light spectrum) to reduced hemoglobin concentrations associated with increasing anemia severity levels. This investigation, which involves skin specimens with distinct biophysical and morphological characteristics, is supported by controlled in silico experiments performed using a predictive light transport model and measured data reported in the biomedical literature. We also propose a noninvasive procedure to be employed in the monitoring of this condition at the point-of-care.

  16. Performance of growing rabbits fed increasing levels of discarded Salvia hispanica L. (chia) seed.

    PubMed

    Rodríguez-Abello, Diana; Ramírez-Avilés, Luis; Navarro-Alberto, Jorge; Zamora-Bustillos, Roberto

    2016-06-01

    This experiment was carried out to evaluate the effect of including five levels of discarded chia seed (DCS) on growth, energy, and economic efficiency in rabbits. Fifty crossbred (New Zealand × Californian) weaning rabbits, weighing 798 ± 170 g, were randomly assigned to the following treatments: 0 % (control), 10 % (Ch10), 20 % (Ch20), 30 % (Ch30), and 40 % (Ch40) of DCS. Ten unsexed rabbits were allocated to each treatment and housed individually in cages; the experimental period was 6 weeks. There were no statistically significant differences between treatments in final body weight (2050 g), body weight gain (30 g/rabbit/day), and carcass weight (1010 g); however, feed intake (91 g/rabbit/day in Ch20 vs. 80 g/rabbit/day in Ch40), feed conversion ratio (2.77 in control and Ch40 vs. 2.95 in Ch10, Ch20, and Ch30), energy conversion ratio (32 MJ/kg in Ch20 vs. 29 MJ/kg on average in control, Ch10, Ch20, Ch30, and Ch40), and economic efficiency (358 % in control vs. 433 % in Ch40) showed differences (P < 0.05) between treatments. Discarded chia seed can be included up to 40 % in growing rabbit diets without any adverse effects on growth and carcass weight, and increased economic efficiency.

  17. Acanthamoeba castellanii metabolites increase the intracellular calcium level and cause cytotoxicity in wish cells.

    PubMed

    Mattana, A; Bennardini, F; Usai, S; Fiori, P L; Franconi, F; Cappuccinelli, P

    1997-08-01

    Previous studies have shown that trophozoites of the pathogenic free-living amoeba Acanthamoeba castellanii rapidly lyse a variety of cells in vitro. However, the role played by cytolitic molecules that may participate in Acanthamoebal cytopathogenicity has yet to be completely elucidated. The aim of this work was to study whether soluble molecules released by A. castellanii trophozoites could induce cytopathic effect in human epithelial cells in vitro. The results obtained indicate that A. castellanii trophozoites constitutively elaborate and release soluble factors that immediately elicit a cytosolic free-calcium increase in target cells. This phenomenon is induced by low molecular weight amoebic metabolites and depends on a transmembrane influx of extracellular calcium. Morphological changes, cytoskeletal damage, cell death and cytolysis followed the elevation of cytosolic free-calcium levels. Calcium ions are very important for cell homeostasis, in fact, they control the functions of a variety of cellular responses, including secretion, cell proliferation and apoptosis. Our results suggest that the substained elevation of the cytosolic free-calcium in response to A. castellanii metabolites might play a fundamental role in target cell damage during Acanthamoeba infections. PMID:9245619

  18. Increased levels of peroxisomal active oxygen-related enzymes in copper-tolerant pea plants

    SciTech Connect

    Palma, J.M.; Gomez, M.; Yanez, J.; Del Rio, L.A.

    1987-10-01

    The effect in vivo of high nutrient levels of copper (240 micromolar) on the activity of different metalloenzymes containing Cu, Mn, Fe, and Zn, distributed in chloroplasts, peroxisomes, and mitochondria, was studied in leaves of two varieties of Pisum sativum L. plants with different sensitivity to copper. The metalloenzymes studied were: cytochrome c oxidase, Mn-superoxide dismutase (Mn-SOD) and Cu,Zn-superoxide dismutase I (Cu,Zn-SOD I), for mitochondria; catalase and Mn-SOD, for peroxisomes; and isozyme Cu,Zn-SOD II for chloroplasts. The activity of mitochondrial SOD isozymes (Mn-SOD and Cu,Zn-SOD I) was very similar in Cu-tolerant and Cu-sensitive plants, whereas cytochrome c oxidase was lower in Cu-sensitive plants. Chloroplastid Cu,Zn-SOD activity was the same in the two plant varieties. In contrast, the peroxisomal Mn-SOD activity was considerably higher in Cu-tolerant than in Cu-sensitive plants, and the activity of catalase was also increased in peroxisomes of Cu-tolerant plants. The higher activities of these peroxisomal active oxygen-related enzymes in Cu-tolerant plants suggest the involvement of reactive oxygen intermediates (O/sub 2//sup -/, OH) in the mechanism of Cu lethality, and also imply a function for peroxisomal Mn-SOD in the molecular mechanisms of plant tolerance to Cu in Pisum sativum L.

  19. Metabolic engineering of Corynebacterium glutamicum for methionine production by removing feedback inhibition and increasing NADPH level.

    PubMed

    Li, Ying; Cong, Hua; Liu, Bingnan; Song, Jinzhu; Sun, Xueying; Zhang, Junzheng; Yang, Qian

    2016-09-01

    Relieving the feedback inhibition of key enzymes in a metabolic pathway is frequently the first step of producer-strain construction by genetic engineering. However, the strict feedback regulation exercised by microorganisms in methionine biosynthesis often makes it difficult to produce methionine at a high level. In this study, Corynebacterium glutamicum ATCC 13032 was metabolically engineered for methionine production. First, the metD gene encoding the methionine uptake system was deleted to achieve extracellular accumulation of methionine. Then, random mutagenesis was performed to remove feedback inhibition by metabolic end-products. The resulting strain C. glutamicum ENM-16 was further engineered to block or decrease competitive branch pathways by deleting the thrB gene and changing the start codon of the dapA gene, followed by point mutations of lysC (C932T) and pyc (G1A, C1372T) to increase methionine precursor supply. To enrich the NADPH pool, glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase in the pentose phosphate pathway were mutated to reduce their sensitivity to inhibition by intracellular metabolites. The resultant strain C. glutamicum LY-5 produced 6.85 ± 0.23 g methionine l(-1) with substrate-specific yield (Y P/S) of 0.08 mol per mol of glucose after 72 h fed-batch fermentation. The strategies described here will be useful for construction of methionine engineering strains. PMID:27255137

  20. Ambroxol suppresses influenza-virus proliferation in the mouse airway by increasing antiviral factor levels.

    PubMed

    Yang, B; Yao, D F; Ohuchi, M; Ide, M; Yano, M; Okumura, Y; Kido, H

    2002-05-01

    The protective effect of ambroxol, a mucolytic agent which has antioxidant properties and stimulates the release of pulmonary surfactant, against influenza-virus proliferation in the airway was investigated in mice. Ambroxol or the vehicle was administered intraperitoneally twice a day for 5-7 days to mice shortly after intranasal infection with a lethal dose of influenza A/Aichi/68 (H3N2) virus, and the survival rate, virus titre and levels of factors regulating virus proliferation in the airway fluid were analysed. Ambroxol significantly suppressed virus multiplication and improved the survival rate of mice. The effect of ambroxol reached a peak at 10 mg x kg(-1) x day(-1), higher doses being less effective. Ambroxol stimulated the release of suppressors of influenza-virus multiplication, such as pulmonary surfactant, mucus protease inhibitor, immunoglobulin (Ig)-A and IgG, although it stimulated the release of a trypsin-type protease that potentiates virus proliferation. In addition, ambroxol transiently suppressed release of the cytokines, tumour necrosis factor-alpha, interferon-gamma and interleukin-12, into airway fluid. Although ambroxol had several negative effects on the host defence system, overall it strikingly increased the concentrations of suppressors of influenza-virus multiplication in the airway.

  1. Increased levels of interleukin-6 exacerbate the dystrophic phenotype in mdx mice

    PubMed Central

    Pelosi, Laura; Berardinelli, Maria Grazia; Forcina, Laura; Spelta, Elisa; Rizzuto, Emanuele; Nicoletti, Carmine; Camilli, Carlotta; Testa, Erika; Catizone, Angela; De Benedetti, Fabrizio; Musarò, Antonio

    2015-01-01

    Duchenne muscular dystrophy (DMD) is characterized by progressive lethal muscle degeneration and chronic inflammatory response. The mdx mouse strain has served as the animal model for human DMD. However, while DMD patients undergo extensive necrosis, the affected muscles of adult mdx mice rapidly regenerates and regains structural and functional integrity. The basis for the mild effects observed in mice compared with the lethal consequences in humans remains unknown. In this study, we provide evidence that interleukin-6 (IL-6) is causally linked to the pathogenesis of muscular dystrophy. We report that forced expression of IL-6, in the adult mdx mice, recapitulates the severe phenotypic characteristics of DMD in humans. Increased levels of IL-6 exacerbate the dystrophic muscle phenotype, sustaining inflammatory response and repeated cycles of muscle degeneration and regeneration, leading to exhaustion of satellite cells. The mdx/IL6 mouse closely approximates the human disease and more faithfully recapitulates the disease progression in humans. This study promises to significantly advance our understanding of the pathogenic mechanisms that lead to DMD. PMID:26251044

  2. Increasing Levels of Restriction in Pharmacoepidemiologic Database Studies of Elderly and Comparison With Randomized Trial Results

    PubMed Central

    Schneeweiss, Sebastian; Patrick, Amanda R.; Stürmer, Til; Brookhart, M. Alan; Avorn, Jerry; Maclure, Malcolm; Rothman, Kenneth J.; Glynn, Robert J.

    2010-01-01

    Background The goal of restricting study populations is to make patients more homogeneous regarding potential confounding factors and treatment effects and thereby achieve less biased effect estimates. Objectives This article describes increasing levels of restrictions for use in pharmacoepidemiology and examines to what extent they change rate ratio estimates and reduce bias in a study of statin treatment and 1-year mortality. Methods The study cohort was drawn from a population of seniors age 65 years and older enrolled in both Medicare and the Pennsylvania Pharmaceutical Assistance Contract for the Elderly (PACE) between 1995 and 2002. We identified all users of statins during the study period and assessed the time until death within 1 year. The following progressive restrictions were applied: (1) study incident drug users only, (2) choose a comparison group most similar to the intervention group, (3) exclude patients with contraindications, (4) exclude patients with low adherence, and (5) restrict to specific high-risk/low-risk subgroups represented in randomized trails (RCTs). Results The basic cohort comprised 122,406 statin users, who were on average 78 years old and predominantly white (93%) and showed an unadjusted rate ratio of 0.32 for statin users. When all 5 restrictions were applied (N = 11,673), the unadjusted rate ratio had increased to 0.72. Multivariable Cox regression adjusted rate ratios increased from 0.62 [95% confidence interval (CI), 0.58–0.66] to 0.79 (95% CI, 0.60–1.03). However, after the first 3 restrictions the effect size changed little. The final estimate is similar to that obtained as a pooled estimate of 3 pravastatin RCTs in patients age 65 years and older. We argue that restrictions 1 through 4 compromised generalizability little. Conclusions In our example of a large database study, restricting to incident drug users, similar comparison groups, patients without contraindication, and to adherent patients was a practical

  3. Intra-molecular cross-linking of acidic residues for protein structure studies.

    SciTech Connect

    Kruppa, Gary Hermann; Young, Malin M.; Novak, Petr; Schoeniger, Joseph S.

    2005-03-01

    can be obtained by exploiting new cross-linker chemistry, increasing the probability that the protein target of choice will yield sufficient distance constraints to develop a structural model.

  4. Characterization of radiation-crosslinked, high-density polyethylene for thermal energy storage applications. [Electron beams

    SciTech Connect

    Whitaker, R.B.; Craven, S.M.; Etter, D.E.; Jendrek, E.F.

    1981-01-01

    This study is directed toward characterization of the crosslinked, form-stable high-density polyethylene (HDPE) pellets produced by electron beam radiation crosslinking, and the effects of crosslinking on crystallinity and heat of fusion. Methods used include differential scanning calorimetry (DSC), Fourier Transform Infrared Spectroscopy (FTIR), and x-ray diffraction measurements. DSC measurements of the heats of fusion (..delta..H/sub f/) of the radiation-crosslinked HDPE showed that while a substantial decrease in ..delta..H/sub f/ occurred after the first melting cycle, slow cooling on recrystallization of the pellets could restore the ..delta..H/sub f/ value to greater than or equal to 95% of that of the uncrosslinked HDPE up to 9.0 Mrad dosage exposure. The form stability of the 9.0-Mrad HDPE was very good even after 500 melt-freeze cycles in ethylene glycol. However, some further decline in ..delta..H/sub f/ was noted and more extensive thermal cycling tests would be required to verify this. X-ray diffraction measurements showed little or no difference in crystallinity among the various radiation-crosslinked HDPE's and the uncrosslinked control HDPE. This indicates the crosslinking occurs primarily in the amorphous regions of the polyethylene. FTIR spectroscopy was used to estimate the relative amounts of crosslinking occurring with the varying radiation dosages, and the uniformity of crosslinking throughout the pellets. The relative amount of crosslinking was based on the ratio of the 965 cm/sup -1/ absorption band to the 909 cm/sup -1/ band. This ratio did increase with increasing radiation dosage: from 1.9 for the crosslinked HDPE dosed with 9.0 Mrad, to 5.3 for that dosed with 18.0 Mrad. Also, the amount of crosslinking from the outside to the center of the pellets was found to be uniform, which would assist in maintaining long-term form stability in the pellets.

  5. Assessment of collagen crosslinking and denaturation for the design of regenerative scaffolds.

    PubMed

    Madaghiele, Marta; Calò, Emanuela; Salvatore, Luca; Bonfrate, Valentina; Pedone, Deborah; Frigione, Mariaenrica; Sannino, Alessandro

    2016-01-01

    Crosslinking and denaturation were two variables that deeply affected the performance of collagen-based scaffolds designed for tissue regeneration. If crosslinking enhances the mechanical properties and the enzymatic resistance of collagen, while masking or reducing the available cell binding sites, denaturation has very opposite effects, as it impairs the mechanical and the enzymatic stability of collagen, but increases the number of exposed cell adhesive domains. The quantification of both crosslinking and denaturation was thus fundamental to the design of collagen-based scaffolds for selected applications. The aim of this work was to investigate the extents of crosslinking and denaturation of collagen-based films upon dehydrothermal (DHT) treatment, that is, one of the most commonly employed methods for zero-length crosslinking that shows the unique ability to induce partial denaturation. Swelling measurements, differential scanning calorimetry, Fourier transform infrared spectroscopy, colorimetric assays for the quantification of primary amines, and mechanical tests were performed to analyze the effect of the DHT temperature on crosslinking and denaturation. In particular, chemically effective and elastically effective crosslink densities were evaluated. Both crosslinking and denaturation were found to increase with the DHT temperature, although according to different trends. The results also showed that DHT treatments performed at temperatures up to 120°C maintained the extent of denaturation under 25%. Coupling a mild DHT treatment with further crosslinking may thus be very useful not only to modulate the crosslink density, but also to induce a limited amount of denaturation, which shows potential to partially compensate the loss of cell binding sites caused by crosslinking.

  6. Gas-Phase Intramolecular Protein Crosslinking via Ion/Ion Reactions: Ubiquitin and a Homobifunctional sulfo-NHS Ester

    NASA Astrophysics Data System (ADS)

    Webb, Ian K.; Mentinova, Marija; McGee, William M.; McLuckey, Scott A.

    2013-05-01

    Gas-phase intra-molecular crosslinking of protein ubiquitin cations has been demonstrated via ion/ion reactions with anions of a homobifunctional N-hydroxysulfosuccinimide (sulfo-NHS) ester reagent. The ion/ion reaction between multiply-protonated ubiquitin and crosslinker monoanions produces a stable, charge-reduced complex. Covalent crosslinking is indicated by the consecutive loss of 2 molecules of sulfo-NHS under ion trap collisional activation conditions. Covalent modification is verified by the presence of covalently crosslinked sequence ions produced by ion-trap collision-induced dissociation of the ion generated from the losses of sulfo-NHS. Analysis of the crosslinked sequence fragments allows for the localization of crosslinked primary amines, enabling proximity mapping of the gas-phase 3-D structures. The presence of two unprotonated reactive sites within the distance constraint of the crosslinker is required for successful crosslinking. The ability to covalently crosslink is, therefore, sensitive to protein charge state. As the charge state increases, fewer reactive sites are available and protein structure is more likely to become extended because of intramolecular electrostatic repulsion. At high charge states, the reagent shows little evidence for covalent crosslinking but does show evidence for `electrostatic crosslinking' in that the binding of the sulfonate groups to the protein is sufficiently strong that backbone cleavages are favored over reagent detachment under ion trap collisional activation conditions.

  7. Gas-phase intramolecular protein crosslinking via ion/ion reactions: ubiquitin and a homobifunctional sulfo-NHS ester.

    PubMed

    Webb, Ian K; Mentinova, Marija; McGee, William M; McLuckey, Scott A

    2013-05-01

    Gas-phase intra-molecular crosslinking of protein ubiquitin cations has been demonstrated via ion/ion reactions with anions of a homobifunctional N-hydroxysulfosuccinimide (sulfo-NHS) ester reagent. The ion/ion reaction between multiply-protonated ubiquitin and crosslinker monoanions produces a stable, charge-reduced complex. Covalent crosslinking is indicated by the consecutive loss of 2 molecules of sulfo-NHS under ion trap collisional activation conditions. Covalent modification is verified by the presence of covalently crosslinked sequence ions produced by ion-trap collision-induced dissociation of the ion generated from the losses of sulfo-NHS. Analysis of the crosslinked sequence fragments allows for the localization of crosslinked primary amines, enabling proximity mapping of the gas-phase 3-D structures. The presence of two unprotonated reactive sites within the distance constraint of the crosslinker is required for successful crosslinking. The ability to covalently crosslink is, therefore, sensitive to protein charge state. As the charge state increases, fewer reactive sites are available and protein structure is more likely to become extended because of intramolecular electrostatic repulsion. At high charge states, the reagent shows little evidence for covalent crosslinking but does show evidence for 'electrostatic crosslinking' in that the binding of the sulfonate groups to the protein is sufficiently strong that backbone cleavages are favored over reagent detachment under ion trap collisional activation conditions. PMID:23463545

  8. Increased viability of odontoblast-like cells subjected to low-level laser irradiation

    NASA Astrophysics Data System (ADS)

    Oliveira, C. F.; Basso, F. G.; Lins, E. C.; Kurachi, C.; Hebling, J.; Bagnato, V. S.; de Souza Costa, C. A.

    2010-07-01

    Studies have shown that the increase of cell metabolism depends on the low level laser therapy (LLLT) parameters used to irradiate the cells. However, the optimal laser dose to up-regulate pulp cell activity remains unknown. Consequently, the aim of this study was to evaluate the metabolic response of odontoblast-like cells (MDPC-23) exposed to different LLLT doses. Cells at 20000 cells/cm2 were seeded in 24-well plates using plain culture medium (DMEM) and were incubated in a humidified incubator with 5% CO2 at 37°C. After 24 h, the culture medium was replaced by fresh DMEM supplemented with 5% (stress by nutritional deficit) or 10% fetal bovine serum (FBS). The cells were exposed to different laser doses from a near infrared diode laser prototype designed to provide a uniform irradiation of the wells. The experimental groups were: G1: 1.5 J/cm2 + 5% FBS; G2: 1.5 J/cm2 + 10% FBS; G3: 5 J/cm2 + 5% FBS; G4: 5 J/cm2 + 10% FBS; G5: 19 J/cm2 + 5% FBS; G6: 19 J/cm2 + 10% FBS. LLLT was performed in 3 consecutive irradiation cycles with a 24-hour interval. Non-irradiated cells cultured in DMEM supplemented with either 5 or 10% FBS served as control groups. The analysis of the metabolic response was performed by the MTT assay 3 h after the last irradiation. G1 presented an increase in SDH enzyme activity and differed significantly (Mann-Whitney test, p < 0.05) from the other groups. Analysis by scanning electron microscopy showed normal cell morphology in all groups. Under the tested conditions, LLLT stimulated the metabolic activity of MDPC-23 cultured in DMEM supplemented with 5% FBS and exposed to a laser dose of 1.5 J/cm2. These findings are relevant for further studies on the action of near infrared lasers on cells with odontoblast phenotype.

  9. Synthesis, characterization and application of biodegradable crosslinked carboxymethyl chitosan/poly(vinyl alcohol) clay nanocomposites.

    PubMed

    Sabaa, Magdy W; Abdallah, Heba M; Mohamed, Nadia A; Mohamed, Riham R

    2015-11-01

    Crosslinked poly(vinyl alcohol) (PVA)/carboxymethyl chitosan (CMCh) nanocomposites were synthesized using terephthaloyl diisothiocyanate crosslinker, in the presence of montmorillonite (MMT), in different ratios of the two matrices. Characterization of nanocomposites was performed using different analyses. Swelling behavior was studied in different buffered solutions. It was found that formation of crosslinked CMCh/PVA hydrogels increased the swellability. Metal ion adsorption has also been investigated. The results indicated that crosslinked CMCh adsorbs various metal ions much more than non crosslinked CMCh. Antimicrobial activity was examined against Gram positive bacteria, against Gram negative bacteria, and also against fungi. Results indicated that most of these nanocomposites exhibited good antimicrobial potency. Degradation study was carried out in Simulated Body Fluid (SBF) for different time periods in order to find out degradation index (Di). Results showed that weight loss of most of the nanocomposites increased as a function of incubation time. PMID:26249602

  10. Effect of Polyethylene Crosslinking and Bearing Design on Wear of Unicompartmental Arthroplasty.

    PubMed

    Netter, Jonathan; Hermida, Juan C; D'Alessio, Jerry; Kester, Mark; D'Lima, Darryl D

    2015-08-01

    Wear and polyethylene damage continue to be important factors affecting outcomes of unicompartmental knee arthroplasty. We compared two design rationales for unicompartmental arthroplasty: fully congruent mobile bearings; or moderately conforming fixed bearings using experimental and computational wear simulation. Experimental wear rates were 3.89 (±0.12) mg/million cycles for the highly crosslinked Triathlon PKR fixed bearing compared to 18.35 (±0.19) mg/million cycles for the low crosslinked Oxford mobile bearing. Finite element analysis was used to calculate the effect of crosslinking and backside wear. Increase in polyethylene crosslinking reduced wear by 68% while backside wear comprised 46% of the total wear in the mobile bearing. Increasing conformity may not be the sole predictor of wear performance and highly crosslinked fixed-bearing polyethylene insert can also provide high wear performance.

  11. Bioaugmentation of Syntrophic Acetate-Oxidizing Culture in Biogas Reactors Exposed to Increasing Levels of Ammonia

    PubMed Central

    Westerholm, Maria; Levén, Lotta

    2012-01-01

    The importance of syntrophic acetate oxidation for process stability in methanogenic systems operating at high ammonia concentrations has previously been emphasized. In this study we investigated bioaugmentation of syntrophic acetate-oxidizing (SAO) cultures as a possible method for decreasing the adaptation period of biogas reactors operating at gradually increased ammonia concentrations (1.5 to 11 g NH4+-N/liter). Whole stillage and cattle manure were codigested semicontinuously for about 460 days in four mesophilic anaerobic laboratory-scale reactors, and a fixed volume of SAO culture was added daily to two of the reactors. Reactor performance was evaluated in terms of biogas productivity, methane content, pH, alkalinity, and volatile fatty acid (VFA) content. The decomposition pathway of acetate was analyzed by isotopic tracer experiments, and population dynamics were monitored by quantitative PCR analyses. A shift in dominance from aceticlastic methanogenesis to SAO occurred simultaneously in all reactors, indicating no influence by bioaugmentation on the prevailing pathway. Higher abundances of Clostridium ultunense and Tepidanaerobacter acetatoxydans were associated with bioaugmentation, but no influence on Syntrophaceticus schinkii or the methanogenic population was distinguished. Overloading or accumulation of VFA did not cause notable dynamic effects on the population. Instead, the ammonia concentration had a substantial impact on the abundance level of the microorganisms surveyed. The addition of SAO culture did not affect process performance or stability against ammonia inhibition, and all four reactors deteriorated at high ammonia concentrations. Consequently, these findings further demonstrate the strong influence of ammonia on the methane-producing consortia and on the representative methanization pathway in mesophilic biogas reactors. PMID:22923397

  12. Increased chromosome fragility as a consequence of blood folate levels, smoking status, and coffee consumption

    SciTech Connect

    Chen, A.T.L.; Reidy, J.A.; Annest, J.L.; Welty, T.K.; Zhou, H. )

    1989-01-01

    Chromosome fragility in 96 h, low-folate cultures was found to be associated with smoking status, coffee consumption, and blood folate level. The higher proportion of cells with chromosome aberrations in cigarette smokers was attributable to lower red cell folate levels in smokers compared with nonsmokers. There was a positive linear relationship between the average cups of coffee consumed per day and the proportion of cells with aberrations. This association was independent of the effects of smoking and red cell folate level. These data suggest that smoking history, coffee consumption, and red cell folate level are important considerations for the design and interpretation of fragile site studies in cancer cytogenetics.

  13. Smokers Beware: Study Shows Increased Cadmium Levels in the Brain May Cause Severe Neurological Disorders

    ERIC Educational Resources Information Center

    King, Angela G.

    2005-01-01

    Tobacco is one crop that accumulates cadmium, making smokers susceptible to higher levels of the metal in their bodies. The findings suggest that even a low-level exposure to a heavy metal like cadmium is likely to cause a change in the functions of neurons in the brain and the behavioral response to drugs of abuse.

  14. Increasing the Validity of Angoff Standards through Analysis of Judge-Level Internal Consistency

    ERIC Educational Resources Information Center

    Clauser, Jerome C.; Clauser, Brian E.; Hambleton, Ronald K.

    2014-01-01

    The purpose of the present study was to extend past work with the Angoff method for setting standards by examining judgments at the judge level rather than the panel level. The focus was on investigating the relationship between observed Angoff standard setting judgments and empirical conditional probabilities. This relationship has been used as a…

  15. Group-Level Selection Increases Cooperation in the Public Goods Game.

    PubMed

    Eckel, Catherine C; Fatas, Enrique; Godoy, Sara; Wilson, Rick K

    2016-01-01

    When groups compete for resources, some groups will be more successful than others, forcing out less successful groups. Group-level selection is the most extreme form of group competition, where the weaker group ceases to exist, becoming extinct. We implement group-level selection in a controlled laboratory experiment in order to study its impact on human cooperation. The experiment uses variations on the standard linear public goods game. Group-level selection operates through competition for survival: the least successful, lowest-earning groups become extinct, in the sense that they no longer are able to play the game. Additional control treatments include group comparison without extinction, and extinction of the least successful individuals across groups. We find that group-level extinction produces very high contributions to the provision of the public good, while group comparison alone or individual extinction fail to cause higher contributions. Our results provide stark evidence that group-level selection enhances within-group cooperation.

  16. Acute increases in night-time plasma melatonin levels following a period of meditation.

    PubMed

    Tooley, G A; Armstrong, S M; Norman, T R; Sali, A

    2000-05-01

    To determine whether a period of meditation could influence melatonin levels, two groups of meditators were tested in a repeated measures design for changes in plasma melatonin levels at midnight. Experienced meditators practising either TM-Sidhi or another internationally well known form of yoga showed significantly higher plasma melatonin levels in the period immediately following meditation compared with the same period at the same time on a control night. It is concluded that meditation, at least in the two forms studied here, can affect plasma melatonin levels. It remains to be determined whether this is achieved through decreased hepatic metabolism of the hormone or via a direct effect on pineal physiology. Either way, facilitation of higher physiological melatonin levels at appropriate times of day might be one avenue through which the claimed health promoting effects of meditation occur.

  17. Remarkably increased resistin levels in anti-AChR antibody-positive myasthenia gravis.

    PubMed

    Zhang, Da-Qi; Wang, Rong; Li, Ting; Li, Xin; Qi, Yuan; Wang, Jing; Yang, Li

    2015-06-15

    Resistin is a pro-inflammatory cytokine involved in the pathogenesis of autoimmune diseases. To investigate serum resistin levels in patients with myasthenia gravis (MG) and determine if there are associations between resistin levels and disease severity, we measured serum resistin levels in 102 patients with anti-acetylcholine receptor antibody-positive MG (AChR-MG). We further analyzed associations between serum resistin levels and clinical variables in patients with MG. Our findings demonstrate that serum resistin levels are elevated in patients with AChR-generalized MG and AChR-MG with thymoma and are correlated with disease severity. Resistin has potential as a useful serum biomarker for inflammation in AChR-MG.

  18. Increased serum levels of interleukin-8 in polyarteritis nodosa and Behçet's disease.

    PubMed

    Freire, Alzírton de Lira; Bertolo, Manoel Barros; de Pinho, Antônio José; Samara, Adil Muhib; Fernandes, Sandra Regina Muchinechi

    2004-06-01

    The pathogenesis of Behçet's disease (BD) and polyarteritis nodosa (PAN) is not yet well established. Endothelial cells have been shown to express chemokines that are involved in inflammatory processes. Interleukin-8 (IL-8) is a potent chemoattractant and activator of neutrophils. We evaluated serum IL-8 levels in patients with PAN and BD. We measured serum IL-8 levels in 21 patients with BD and 16 with PAN. Sera from 30 age-matched healthy blood donors were used as normal controls. Serum IL-8 levels were measured by an enzyme-linked immunosorbent assay (ELISA). The mean serum IL-8 level of the active BD (1522.31 pg/ml) and that of the active PAN (654.8 pg/ml) was significantly higher than that of the normal controls (40.39 pg/ml, P <0.05). There was no difference in mean serum IL-8 levels between patients with inactive disease and normal controls. We found higher serum levels of IL-8 in those patients with more severe disease. These results suggest that IL-8 may play a role in the pathogenesis of PAN and/or BD. Our study also suggests a possible relation between serum IL-8 levels and the severity of these diseases.

  19. Increased sea level promotes coral cover on shallow reef flats in the Andaman Sea, eastern Indian Ocean

    NASA Astrophysics Data System (ADS)

    Brown, B. E.; Dunne, R. P.; Phongsuwan, N.; Somerfield, P. J.

    2011-12-01

    Sea level in the Indian Ocean is subject to considerable temporal and spatial variabilities. During the period 1960-2009 at Phuket, Thailand, in the NE Indian Ocean, mean sea level increased by 2.7 mm y-1. Regular monitoring of coral cover on fringing reef flats at Phuket since 1979 revealed a sensitive response of this habitat to both transient sea-level depressions and sea-level elevation. Since 1987 when more frequent sampling began, coral cover was positively correlated with the mean sea level experienced over the preceding months. Changing mean sea level explained a high proportion of the observed variation in cover, with overall increasing sea levels and a lack of negative sea-level anomalies promoting cover on the outer reef flats. Concomitantly, there have been no changes in reef community structure or any apparent shifts in zonation patterns across the reef. While future benefits of continued increases in mean sea level on reef flats in the region will be constrained by the frequency and intensity of sea-level depressions associated with the Indian Ocean Dipole, and bleaching events, the overall picture for these shallow reefs is a positive one as they respond to increasing sea level and show rapid recovery from environmental disturbances.

  20. Intra-molecular cross-linking of acidic residues for protein structure studies.

    PubMed

    Novak, Petr; Kruppa, Gary H

    2008-01-01

    Intra-molecular cross-linking has been suggested as a method of obtaining distance constraints that would help to develop structural models of proteins. Recent work published on intra-molecular cross-linking for protein structural studies has employed commercially available primary amine (lysine, the amino terminus) selective reagents. Previous work using these cross-linkers has shown that for several proteins of known structure, the number of cross-links that can be obtained experimentally may be small compared to what would be expected from the known structure, due to the relative reactivity, distribution and solvent accessibility of the lysines in the protein sequence. To overcome these limitations, we have investigated the use of cross-linking reagents that can react with other reactive side chains in proteins. We used 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) to activate the carboxylic acid containing residues, aspartic acid (D), glutamic acid (E) and the carboxy terminus (O), for cross-linking reactions. Once activated, the DEO side chains can react to form "zero-length" cross-links with nearby primary amine containing residues, lysines (K) and the amino terminus (X), via the formation of a new amide bond. We also show that the EDC-activated DEO side chains can be cross-linked to each other using dihydrazides, two hydrazide moieties connected by an alkyl cross-linker arm of variable length. Using these reagents, we have found three new "zero-length" cross-links in ubiquitin consistent with its known structure (M1-E16, M1-E18 and K63-E64). Using the dihydrazide cross-linkers, we have identified two new cross-links (D21-D32 and E24-D32) unambiguously. Using a library of dihydrazide cross-linkers with varying arm length, we have shown that there is a minimum arm length required for the DEO-DEO cross-links of 5.8 A. These results show that additional structural information can be obtained by exploiting new cross-linker chemistry

  1. Autophagy promotes DNA-protein crosslink clearance.

    PubMed

    Mu, Haibo; Liu, Qianjin; Niu, Hong; Wang, Dongdong; Tang, Jiangjiang; Duan, Jinyou

    2016-02-01

    Toxic DNA-protein crosslinks (DPCs) can result from exposure to radiation or chemotherapeutic agents. DPCs can also accumulate during aging or stress. However, the cellular mechanisms underlying clearance of DPCs remain largely unknown. Here, we have identified an important role of autophagy in the processing of DPCs induced by three representative agents: formaldehyde, a chemical used widely in industry; UV light; and camptothecin, a cytotoxic anticancer drug. Autophagy inhibitors, 3-methyladenine (3-MA) or chloroquine (CQ), promoted the accumulation of DPCs in damaged cells and injured organs. siRNA-mediated silencing of Atg5 or Atg7, two essential components for the formation of the autophagosome, gave similar results. In contrast, the autophagy inducer rapamycin (RAP) attenuated DPCs in vitro and in vivo. Our findings reveal the importance of autophagy in controlling the level of DPCs, and may open up a new avenue for understanding the formation and clearance of this detrimental DNA adduct. PMID:26921017

  2. Peanut consumption increases levels of plasma very long chain fatty acids in humans.

    PubMed

    Lam, Christina; Wong, Derek; Cederbaum, Stephen; Lim, Bennie; Qu, Yong

    2012-11-01

    Peanut consumption has been suspected of raising plasma very long chain fatty acid (VLCFA) levels in humans. The effect of peanut consumption on VLCFAs was studied in six human subjects. After 3 to 4h of peanut butter ingestion, plasma C26:0 and C26:0/C22:0 were found to be significantly elevated to levels seen in patients with peroxisomal disorders. These levels returned to normal within 12h. Peanut consumption needs to be accounted for when interpreting VLCFAs. PMID:22864056

  3. Pontine Reticular Formation (PnO) Administration of Hypocretin-1 Increases PnO GABA Levels and Wakefulness

    PubMed Central

    Watson, Christopher J.; Soto-Calderon, Haideliza; Lydic, Ralph; Baghdoyan, Helen A.

    2008-01-01

    Study Objectives: GABAergic transmission in the oral part of the pontine reticular formation (PnO) increases wakefulness. The hypothalamic peptide hypocretin-1 (orexin A) promotes wakefulness, and the PnO receives hypocretinergic input. The present study tested the hypothesis that PnO administration of hypocretin-1 increases PnO GABA levels and increases wakefulness. This study also tested the hypothesis that wakefulness is either increased or decreased, respectively, by PnO administration of drugs known to selectively increase or decrease GABA levels. Design: A within-subjects design was used for microdialysis and microinjection experiments. Setting: University of Michigan. Patients or Participants: Experiments were performed using adult male Crl:CD® (SD)IGS BR (Sprague-Dawley) rats (n = 46). Interventions: PnO administration of hypocretin-1, nipecotic acid (a GABA uptake inhibitor that increases extracellular GABA levels), 3-mercaptopropionic acid (a GABA synthesis inhibitor that decreases extracellular GABA levels; 3-MPA), and Ringer solution (vehicle control). Measurements and Results: Dialysis administration of hypocretin-1 to the PnO caused a statistically significant, concentration-dependent increase in PnO GABA levels. PnO microinjection of hypocretin-1 or nipecotic acid caused a significant increase in wakefulness and a significant decrease in non-rapid eye movement (NREM) sleep and REM sleep. Microinjecting 3-MPA into the PnO caused a significant increase in NREM sleep and REM sleep and a significant decrease in wakefulness. Conclusions: An increase or a decrease in PnO GABA levels causes an increase or decrease, respectively, in wakefulness. Hypocretin-1 may promote wakefulness, at least in part, by increasing GABAergic transmission in the PnO. Citation: Watson CJ; Soto-Calderon H; Lydic R; Baghdoyan HA. Pontine reticular formation (PnO) administration of hypocretin-1 increases PnO GABA levels and wakefulness. SLEEP 2008;31(4):453-464. PMID:18457232

  4. Processing and characterization of benzocyclobutene (BCB)-functionalized thermally crosslinkable copolymers

    NASA Astrophysics Data System (ADS)

    Jiang, Tao

    The objective of this research has been to examine the processing, microstructure and physical properties of benzocyclobutene (BCB) functionalized copolymers. The approach was based on incorporating XTA, a BCB modified derivative of terephthalic acid, into the polymer backbone and then inducing crosslinking by heat treatment after the polymer has been formed into various shapes. The primary focus of the work was to investigate aromatic polyamides (aramids) such as poly(p-phenylene terephthalamide) (PPTA or Kevlarsp°ler) and poly(m-phenylene isophthalamide) (MPDI or Nomexsp°ler). It was anticipated that crosslinking would increase the inter-chain interactions between PPTA molecules and thus improve its compressive strength as well as other properties including creep, solvent resistance and flame resistance. PPTA-co-XTA copolymers exhibited lyotropic nematic liquid crystalline behavior. Highly oriented fibers were obtained using dry-jet wet spinning techniques, and they could be crosslinked via heat treatment between 320 and 420sp°C. Crosslinked fibers possessed higher tensile modulus than their as-spun counterparts. However, for high XTA-content materials, the tensile strength and toughness tended to decrease with increasing extent of heat treatment, which was attributed to degradative chain scission. MPDI-co-XTA copolymers were processed from isotropic solutions. The thermally crosslinkable copolymers demonstrated improved solvent resistance and dimensional stability at elevated temperatures. Crosslinking led to increased tensile modulus and decreased toughness and elongation at break. Molecular modeling established that with low XTA content the overall structure of MPDI-co-XTA copolymers was mostly unchanged from that of the neat MPDI and that the incorporated XTA unit introduced only local perturbations. Spectroscopic studies suggested that BCB crosslinked predominantly via stilbene junctions. Free radicals were found to form after crosslinking and might cause

  5. Arthropod food webs become increasingly lipid-limited at higher trophic levels.

    PubMed

    Wilder, Shawn M; Norris, Michael; Lee, Raymond W; Raubenheimer, David; Simpson, Stephen J

    2013-07-01

    Understanding why food chains are relatively short in length has been an area of research and debate for decades. We tested if progressive changes in the nutritional content of arthropods with trophic position limit the availability of a key nutrient, lipid, for carnivores. Arthropods at higher trophic levels had progressively less lipid and more protein in their bodies compared with arthropods at lower trophic levels. The nutrients present in arthropod bodies were directly related to the nutrients that predators extracted when feeding on those arthropods. As a consequence, nutrient assimilation shifted from lipid-biased to protein-biased as arthropods ascended trophic levels from herbivores to secondary carnivores. Successive changes in the nutritional consequences of predation may ultimately set an upper limit on the number of trophic levels in arthropod communities. Further work is needed to examine the influence of lipid and other nutrients on food web traits in a range of ecosystems.

  6. Increased serum levels of macrophage migration inhibitory factor (MIF) in patients with microscopic polyangiitis

    PubMed Central

    Kanemitsu, Hirohito; Matsunawa, Mizuho; Wakabayashi, Kuninobu; Sato, Michihito; Takahashi, Ryo; Odai, Tsuyoshi; Isozaki, Takeo; Yajima, Nobuyuki; Miwa, Yusuke; Kasama, Tsuyoshi

    2009-01-01

    Objective To test the hypothesis that macrophage migration inhibitory factor (MIF) is involved in the disease activity of systemic vasculitis. Methods Patients with systemic vasculitis were divided into three groups based on the size of the affected vessels. Microscopic polyangiitis (MPA) was considered as small vessel vasculitis (SVV), polyarteritis nodosa as medium-sized vessel vasculitis (MVV), and giant cell arteritis and Takayasu arteritis as large vessel vasculitis (LVV). Sera from patients with systemic vasculitis and healthy individuals were collected, and MIF levels were measured using an enzyme-linked immunosorbent assay. Disease activity of vasculitis was assessed using the Birmingham Vasculitis Activity Score (BVAS). Results Serum MIF levels were significantly higher in the vasculitis patients than in healthy individuals. Among the vasculitis patients, MIF levels were significantly higher in patients in the SVV group (median; 4161.7 pg/ml) than in the other groups (MVV; 1443.2 pg/ml and LVV; 1576.7 pg/ml). In patients with MPA, a positive correlation was observed between serum MIF levels and CRP levels and disease activity (BVAS). Notably, serum MIF levels were significantly diminished after clinical improvement. Conclusions Our findings suggest that MIF may have an important role in small vessel vasculopathy and serve as a useful serologic marker of MPA disease activity.

  7. Construction of a multi-functional cryogenic propellant tank with cross-linked silica aerogel

    NASA Astrophysics Data System (ADS)

    Reinheimer, Preston Glenn

    Aerogels are low-density nanostructured porous materials, whose practical applications have been limited by their poor mechanical properties. Crosslinking the nanoparticle building blocks of silica aerogels with polymeric tethers increases both the modulus and the strength significantly. The polymer coating preserves the mesoporous structure of the silica framework while retaining its low thermal conductivity. The uniqueness of crosslinked silica aerogel has load carrying capabilities in which are determined in tensile, compression and flexural bending tests. Crosslinked silica aerogel testing displays specific compressive strength of 389000 Nm/Kg. Ballistic testing of crosslinked silica aerogel also corroborates its mechanical properties displaying a ballistic limit up to 80 m/s. Its thermal conductivity at 0.041 W/mK supports the use of crosslinked silica aerogel in cryogenic fuel cell applications. Manufacturing practices have been evaluated to obtain an optimal process which reduces time, money and difficulty.

  8. Collagen cross-linking of skin in patients with amyotrophic lateral sclerosis

    NASA Technical Reports Server (NTRS)

    Ono, S.; Yamauchi, M.

    1992-01-01

    Collagen cross-links of skin tissue (left upper arm) from 11 patients with amyotrophic lateral sclerosis (ALS) and 9 age-matched control subjects were quantified. It was found that patients with ALS had a significant reduction in the content of an age-related, stable cross-link, histidinohydroxylysinonorleucine, that was negatively correlated with the duration of illness. The contents of sodium borohydride-reducible labile cross-links, dehydro-hydroxylysinonorleucine and dehydro-histidinohydroxymerodesmosine, were significantly increased and were positively associated with the duration of illness (r = 0.703, p less than 0.05 and r = 0.684, p less than 0.05, respectively). The results clearly indicate that during the course of ALS, the cross-linking pathway of skin collagen runs counter to its normal aging, resulting in a "rejuvenation" phenomenon of skin collagen. Thus, cross-linking of skin collagen is affected in ALS.

  9. Crosslinking and degradation of polypropylene by electron beam irradiation in the presence of trifunctional monomers

    NASA Astrophysics Data System (ADS)

    Han, Do Hung; Shin, Seung-Ho; Petrov, Serguei

    2004-02-01

    Homo-polypropylene (HPP) and random terpolymer of propylene with 2% ethylene and 1% 1-butene by weight (RTPP) can be crosslinked with relatively high gel contents even at doses less than 20 kGy, when using trimethylpropanetriacrylate (TMPTA) and triallylcyanuate (TAC) as crosslinking agents. At high doses, HPP with TMPTA degrades more compared to HPP with TAC or RTPP with TMPTA, resulting in a significant increase of the melt index. Heat of fusion of the irradiated polypropylenes (PPs) indicates that the crosslinking and degradation are likely to have little effect on the crystallinity of the PP. Larger amounts of TMPTA in HPP gave rise to more degradation than crosslinking, since excesses of monomer prohibit crosslinking through homo-polymerization.

  10. Differential expression of human lysyl hydroxylase genes, lysine hydroxylation, and cross-linking of type I collagen during osteoblastic differentiation in vitro

    NASA Technical Reports Server (NTRS)

    Uzawa, K.; Grzesik, W. J.; Nishiura, T.; Kuznetsov, S. A.; Robey, P. G.; Brenner, D. A.; Yamauchi, M.

    1999-01-01

    The pattern of lysyl hydroxylation in the nontriple helical domains of collagen is critical in determining the cross-linking pathways that are tissue specific. We hypothesized that the tissue specificity of type I collagen cross-linking is, in part, due to the differential expression of lysyl hydroxylase genes (Procollagen-lysine,2-oxyglutarate,5-dioxygenase 1, 2, and 3 [PLOD1, PLOD2, and PLOD3]). In this study, we have examined the expression patterns of these three genes during the course of in vitro differentiation of human osteoprogenitor cells (bone marrow stromal cells [BMSCs]) and normal skin fibroblasts (NSFs). In addition, using the medium and cell layer/matrix fractions in these cultures, lysine hydroxylation of type I collagen alpha chains and collagen cross-linking chemistries have been characterized. High levels of PLOD1 and PLOD3 genes were expressed in both BMSCs and NSFs, and the expression levels did not change in the course of differentiation. In contrast to the PLOD1 and PLOD3 genes, both cell types showed low PLOD2 gene expression in undifferentiated and early differentiated conditions. However, fully differentiated BMSCs, but not NSFs, exhibited a significantly elevated level (6-fold increase) of PLOD2 mRNA. This increase coincided with the onset of matrix mineralization and with the increase in lysyl hydroxylation in the nontriple helical domains of alpha chains of type I collagen molecule. Furthermore, the collagen cross-links that are derived from the nontriple helical hydroxylysine-aldehyde were found only in fully differentiated BMSC cultures. The data suggests that PLOD2 expression is associated with lysine hydroxylation in the nontriple helical domains of collagen and, thus, could be partially responsible for the tissue-specific collagen cross-linking pattern.

  11. Optimization model for UV-Riboflavin corneal cross-linking

    NASA Astrophysics Data System (ADS)

    Schumacher, S.; Wernli, J.; Scherrer, S.; Bueehler, M.; Seiler, T.; Mrochen, M.

    2011-03-01

    Nowadays UV-cross-linking is an established method for the treatment of keraectasia. Currently a standardized protocol is used for the cross-linking treatment. We will now present a theoretical model which predicts the number of induced crosslinks in the corneal tissue, in dependence of the Riboflavin concentration, the radiation intensity, the pre-treatment time and the treatment time. The model is developed by merging the difussion equation, the equation for the light distribution in dependence on the absorbers in the tissue and a rate equation for the polymerization process. A higher concentration of Riboflavin solution as well as a higher irradiation intensity will increase the number of induced crosslinks. However, performed stress-strain experiments which support the model showed that higher Riboflavin concentrations (> 0.125%) do not result in a further increase in stability of the corneal tissue. This is caused by the inhomogeneous distribution of induced crosslinks throughout the cornea due to the uneven absorption of the UV-light. The new model offers the possibility to optimize the treatment individually for every patient depending on their corneal thickness in terms of efficiency, saftey and treatment time.

  12. County-level analysis of the impact of temperature and population increases on California wildfire data

    USGS Publications Warehouse

    Baltar, M.; Keeley, Jon E.; Schoenberg, F.P.

    2013-01-01

    The extent to which the apparent increase in wildfire incidence and burn area in California from 1990 to 2006 is affected by population and temperature increases is examined. Using generalized linear models with random effects, we focus on the estimated impacts of increases in mean daily temperatures and populations in different counties on wildfire in those counties, after essentially controlling for the overall differences between counties in their overall mean temperatures and populations. We find that temperature increase appears to have a significant positive impact on both total burn area and number of observed wildfires. Population growth appears to have a much less pronounced impact on total burn area than do annual temperature increases, and population growth appears to be negatively correlated with the total number of observed wildfires. These effects are especially pronounced in the winter season and in Southern California counties.

  13. Group-Level Selection Increases Cooperation in the Public Goods Game

    PubMed Central

    Eckel, Catherine C.; Fatas, Enrique; Godoy, Sara

    2016-01-01

    When groups compete for resources, some groups will be more successful than others, forcing out less successful groups. Group-level selection is the most extreme form of group competition, where the weaker group ceases to exist, becoming extinct. We implement group-level selection in a controlled laboratory experiment in order to study its impact on human cooperation. The experiment uses variations on the standard linear public goods game. Group-level selection operates through competition for survival: the least successful, lowest-earning groups become extinct, in the sense that they no longer are able to play the game. Additional control treatments include group comparison without extinction, and extinction of the least successful individuals across groups. We find that group-level extinction produces very high contributions to the provision of the public good, while group comparison alone or individual extinction fail to cause higher contributions. Our results provide stark evidence that group-level selection enhances within-group cooperation. PMID:27574971

  14. Increased IL-35 serum levels in systemic sclerosis and association with pulmonary interstitial involvement.

    PubMed

    Dantas, Andréa Tavares; Gonçalves, Sayonara Maria Calado; Pereira, Michelly Cristiny; Gonçalves, Rafaela Silva Guimarães; Marques, Cláudia Diniz Lopes; Rego, Moacyr Jesus Barreto de Melo; Pitta, Ivan da Rocha; Duarte, Angela Luzia Branco Pinto; Pitta, Maira Galdino da Rocha

    2015-09-01

    The objective of this study is to assess the serum IL-35 level and its association with clinical manifestations in patients with systemic sclerosis (SSc). IL-35 serum levels were measured by ELISA from 56 patients with SSc and 53 healthy controls. Association of IL-35 serum levels were sought with clinical parameters. Serum IL-35 levels were significantly higher in SSc patients (5.08 ± 0.76 pg/ml) than in healthy individuals (1.89 ± 0.69 pg/ml; p < 0.0001). Patients with lung fibrosis had higher IL-35 levels than those without fibrosis (7.75 ± 1.36 and 3.08 ± 0.70 pg/ml, respectively, p = 0.0022). IL-35 is elevated in the serum of patients with SSc and is associated with lung fibrosis. Our findings suggest that this cytokine can have a role in fibrotic diseases, but further studies are needed to address the role of IL-35 in the pathogenesis of SSc.

  15. Group-Level Selection Increases Cooperation in the Public Goods Game.

    PubMed

    Eckel, Catherine C; Fatas, Enrique; Godoy, Sara; Wilson, Rick K

    2016-01-01

    When groups compete for resources, some groups will be more successful than others, forcing out less successful groups. Group-level selection is the most extreme form of group competition, where the weaker group ceases to exist, becoming extinct. We implement group-level selection in a controlled laboratory experiment in order to study its impact on human cooperation. The experiment uses variations on the standard linear public goods game. Group-level selection operates through competition for survival: the least successful, lowest-earning groups become extinct, in the sense that they no longer are able to play the game. Additional control treatments include group comparison without extinction, and extinction of the least successful individuals across groups. We find that group-level extinction produces very high contributions to the provision of the public good, while group comparison alone or individual extinction fail to cause higher contributions. Our results provide stark evidence that group-level selection enhances within-group cooperation. PMID:27574971

  16. Increased IL-35 serum levels in systemic sclerosis and association with pulmonary interstitial involvement.

    PubMed

    Dantas, Andréa Tavares; Gonçalves, Sayonara Maria Calado; Pereira, Michelly Cristiny; Gonçalves, Rafaela Silva Guimarães; Marques, Cláudia Diniz Lopes; Rego, Moacyr Jesus Barreto de Melo; Pitta, Ivan da Rocha; Duarte, Angela Luzia Branco Pinto; Pitta, Maira Galdino da Rocha

    2015-09-01

    The objective of this study is to assess the serum IL-35 level and its association with clinical manifestations in patients with systemic sclerosis (SSc). IL-35 serum levels were measured by ELISA from 56 patients with SSc and 53 healthy controls. Association of IL-35 serum levels were sought with clinical parameters. Serum IL-35 levels were significantly higher in SSc patients (5.08 ± 0.76 pg/ml) than in healthy individuals (1.89 ± 0.69 pg/ml; p < 0.0001). Patients with lung fibrosis had higher IL-35 levels than those without fibrosis (7.75 ± 1.36 and 3.08 ± 0.70 pg/ml, respectively, p = 0.0022). IL-35 is elevated in the serum of patients with SSc and is associated with lung fibrosis. Our findings suggest that this cytokine can have a role in fibrotic diseases, but further studies are needed to address the role of IL-35 in the pathogenesis of SSc. PMID:26160266

  17. Increase of serum fractalkine and fractalkine gene expression levels in sickle cell disease patients.

    PubMed

    Unal, Selma; Ozdemir, Ozlem; Ozcimen, Ahmet Ata; Oztas, Yesim

    2015-02-01

    In the present study, we examined the role of fractalkine (Fkn), a member of the chemokine family, in the pathogenesis of sickle cell disease (SCD). Eighty-seven children with sickle cell disease and 55 healthy children were enrolled in the study. Complete blood counts, serum levels of C-reactive protein, tumor necrosis factor-α, interferon-γ and fractalkine, and gene expression levels of Fkn were investigated. Serum Fkn levels and Fkn gene expression values were significantly higher in the SCD group compared to control group (P < 0.05). The findings of elevated serum Fkn and Fkn gene expression in both vaso-occlusive crisis and stable forms of SCD suggest that this chemokine may be involved in the pathogenesis of inflammation observed in SCD. This study is the first to our knowledge to describe the relationship of Fkn and inflammation in SCD.

  18. Increased levels of serum neopterin in attention deficit/hyperactivity disorder (ADHD).

    PubMed

    Ceylan, Mehmet Fatih; Uneri, Ozden Sukran; Guney, Esra; Ergin, Merve; Alisik, Murat; Goker, Zeynep; Senses Dinc, Gulser; Karaca Kara, Fatma; Erel, Ozcan

    2014-08-15

    Attention deficit/hyperactivity disorder (ADHD) is the most frequently occurring neuropsychiatric disorder in childhood with an etiology that is not fully understood. A number of reviews that have addressed the neurobiology of ADHD have focused on imaging and genetics. Relatively little attention has been given to factors/mechanisms involved in the brain dysfunction. We suggest that changes in cellular immunity may be involved. Neopterin is a good indicator of cellular immunity, and we evaluated serum levels of neopterin in patients with ADHD. The study group consisted of 49 patients with ADHD. An age- and gender-matched control group was composed of 31 healthy subjects. Venous blood samples were collected, and the levels of neopterin were measured. The levels of neopterin were significantly higher in ADHD than in the comparison subjects. Cellular immunity may have a role in the etiopathogenesis of ADHD.

  19. A Phospholipid-Protein Complex from Antarctic Krill Reduced Plasma Homocysteine Levels and Increased Plasma Trimethylamine-N-Oxide (TMAO) and Carnitine Levels in Male Wistar Rats

    PubMed Central

    Bjørndal, Bodil; Ramsvik, Marie S.; Lindquist, Carine; Nordrehaug, Jan E.; Bruheim, Inge; Svardal, Asbjørn; Nygård, Ottar; Berge, Rolf K.

    2015-01-01

    Seafood is assumed to be beneficial for cardiovascular health, mainly based on plasma lipid lowering and anti-inflammatory effects of n-3 polyunsaturated fatty acids. However, other plasma risk factors linked to cardiovascular disease are less studied. This study aimed to penetrate the effect of a phospholipid-pr