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Sample records for albumin solutions implications

  1. Differential solubility of curcuminoids in serum and albumin solutions: implications for analytical and therapeutic applications

    PubMed Central

    Quitschke, Wolfgang W

    2008-01-01

    Background Commercially available curcumin preparations contain a mixture of related polyphenols, collectively referred to as curcuminoids. These encompass the primary component curcumin along with its co-purified derivatives demethoxycurcumin and bisdemethoxycurcumin. Curcuminoids have numerous biological activities, including inhibition of cancer related cell proliferation and reduction of amyloid plaque formation associated with Alzheimer disease. Unfortunately, the solubility of curcuminoids in aqueous solutions is exceedingly low. This restricts their systemic availability in orally administered formulations and limits their therapeutic potential. Results Methods are described that achieve high concentrations of soluble curcuminoids in serum. Solid curcuminoids were either mixed directly with serum, or they were predissolved in dimethyl sulfoxide and added as aliquots to serum. Both methods resulted in high levels of curcuminoid-solubility in mammalian sera from different species. However, adding aliquots of dimethyl sulfoxide-dissolved curcuminoids to serum proved to be more efficient, producing soluble curcuminoid concentrations of at least 3 mM in human serum. The methods also resulted in the differential solubility of individual curcuminoids in serum. The addition of dimethyl sulfoxide-dissolved curcuminoids to serum preferentially solubilized curcumin, whereas adding solid curcuminoids predominantly solubilized bisdemethoxycurcumin. Either method of solubilization was equally effective in inhibiting dose-dependent HeLa cell proliferation in culture. The maximum concentration of curcuminoids achieved in serum was at least 100-fold higher than that required for inhibiting cell proliferation in culture and 1000-fold higher than the concentration that has been reported to prevent amyloid plaque formation associated with Alzheimer disease. Curcuminoids were also highly soluble in solutions of purified albumin, a major component of serum. Conclusion These

  2. Hydrophobic Volume Effects in Albumin Solutions.

    PubMed

    Schrade, P.; Klein, H.; Egry, I.; Ademovic, Z.; Klee, D.

    2001-02-15

    Density measurements of aqueous albumin solutions as a function of concentration and temperature are reported. The solvents were H(2)O, D(2)O, and a physiological H(2)O-based buffer. An anomaly of the density at very small concentrations of albumin in D(2)O was found. Furthermore, the partial specific volume of albumin is remarkably different in D(2)O and H(2)O. We attribute both effects to structural differences of the solvents. Copyright 2001 Academic Press.

  3. Sodium chloride crystallization from drying drops of albumin-salt solutions with different albumin concentrations

    NASA Astrophysics Data System (ADS)

    Yakhno, T. A.

    2015-11-01

    The salt nature of crystalline structures resulting from drying albumin-salt solutions with a low (<1 wt %) and high (7 and 9 wt %) concentration of albumin and a NaCl concentration kept at a physiological level (0.9 wt %) is experimentally substantiated. Such a conclusion is drawn from the dynamics of phase transitions, morphological studies, and differences between the physicochemical properties of albumin and salt. Obtained data give a deeper insight into the albumin and salt distributions in drying liquids.

  4. Adsorption of albumin on prosthetic materials: implication for tribological behavior.

    PubMed

    Serro, A P; Gispert, M P; Martins, M C L; Brogueira, P; Colaço, R; Saramago, B

    2006-09-01

    The orthopedic prosthesis used to substitute damaged natural joints are lubricated by a pseudosynovial fluid that contains biological macromolecules with potential boundary lubrication properties. Proteins are some of those macromolecules whose role in the lubrication process is not yet completely understood. In a previous work, we investigated the influence of the presence of albumin, the major synovial protein, upon the tribological behavior of three of the most used pairs of artificial joint materials: ultra high molecular weight polyethylene (UHMWPE) against counterfaces of alumina, CoCrMo alloy, and 316L stainless steel. Albumin was found to cause a significant decrease in the friction coefficient when the counterfaces were metallic because transfer of UHMWPE was avoided, but this effect was much weaker in the case of alumina. The objective of the present work was to look for an explanation for these differences in tribological behavior in terms of albumin adsorption. With this goal, studies on adsorption of bovine serum albumin (BSA) on the counterface materials, from a biological model fluid (Hanks' balanced salt solution), were carried out using radiolabeled albumin ((125)I-BSA), X-ray photoelectron spectroscopy, and atomic force microscopy. The conclusion from all techniques is that the driving force for albumin adsorption is higher on the metals than on alumina. These results confirm that the greater the amount of protein adsorbed on the counterface, the more efficient is the protection against the transfer of polymeric film to the counterface.

  5. Interaction between pirenoxine and bovine serum albumin in aqueous solution.

    PubMed

    Liao, Zhixi; Yu, Xianyong; Yao, Qing; Yi, Pinggui

    2014-08-14

    This work concerns the interaction of prenoxine sodium (PRX) and bovine serum albumin (BSA), which was conducted by spectroscopic means: fluorescence spectra, ultraviolet-visible spectra (UV-vis) and circular dichroism spectra (CD spectra) in physiological conditions. The results revealed the PRX can quench the fluorescence of BSA remarkably in aqueous solution. The quench mechanism has been obtained after corrected the fluorescence intensities for inner filter effects. The binding constants (Ka) were calculated according to the relevant fluorescence data at different temperatures. Moreover, from a series of analyses, we have obtained the binding sites, the binding distance and binding force. The effect of PRX on the conformation of BSA has been analyzed using synchronous fluorescence under experimental conditions. In addition, the CD spectra proved that the secondary structure of BSA changed in the presence of PRX in aqueous solution.

  6. Interaction between pirenoxine and bovine serum albumin in aqueous solution

    NASA Astrophysics Data System (ADS)

    Liao, Zhixi; Yu, Xianyong; Yao, Qing; Yi, Pinggui

    2014-08-01

    This work concerns the interaction of prenoxine sodium (PRX) and bovine serum albumin (BSA), which was conducted by spectroscopic means: fluorescence spectra, ultraviolet-visible spectra (UV-vis) and circular dichroism spectra (CD spectra) in physiological conditions. The results revealed the PRX can quench the fluorescence of BSA remarkably in aqueous solution. The quench mechanism has been obtained after corrected the fluorescence intensities for inner filter effects. The binding constants (Ka) were calculated according to the relevant fluorescence data at different temperatures. Moreover, from a series of analyses, we have obtained the binding sites, the binding distance and binding force. The effect of PRX on the conformation of BSA has been analyzed using synchronous fluorescence under experimental conditions. In addition, the CD spectra proved that the secondary structure of BSA changed in the presence of PRX in aqueous solution.

  7. Influence of albumin on the electrochemical behaviour of Zr in phosphate buffered saline solutions.

    PubMed

    Wang, Lu-Ning; Huang, Xian-Qiu; Shinbine, Alyssa; Luo, Jing-Li

    2013-02-01

    The corrosion behaviour of Zr in phosphate buffered saline (PBS) solutions with various concentrations (0-4 g L(-1)) of albumin was studied by electrochemical techniques and surface analysis. Addition of albumin to PBS solutions moved the open circuit potential (OCP) to less nobler direction. OCP, polarization resistance and impedance increased and the corrosion current decreased over immersion duration. At early stages of immersion, the resistance was increased with the concentration of albumin because of the high adsorption kinetics of albumin on metal. After the long term immersion, the resistance in PBS without albumin was higher than PBS with albumin owing to the anodic dissolution effect of albumin on metal. According to the analysis of effective capacitances, a normal distribution of time-constants was proposed to estimate the surface film on Zr. A corrosion mechanism of Zr in PBS with different albumin was proposed based on electrochemical analysis.

  8. Egg on their faces. The story of human albumin solution.

    PubMed

    Roberts, Ian; Bunn, Frances

    2002-03-01

    In 1998, the Cochrane Injuries Group published the results of a systematic review of human albumin administration in critically ill patients. The results showed that the risk of death in patients receiving albumin was 14%, and the risk of death in patients not receiving albumin was 8%, suggesting that for every 17 critically ill patients treated with albumin there is one extra death. The results were widely reported in the television and print media throughout the world and stimulated an immediate response from the drug regulatory agencies, the plasma products industry, and the medical profession. Despite vigorous attempts by the plasma products industry to limit the effect of the systematic review on albumin sales, the use of albumin declined steeply, showing that evidence from systematic reviews can have an important effect on clinical care.

  9. The role of albumin receptors in regulation of albumin homeostasis: Implications for drug delivery.

    PubMed

    Bern, Malin; Sand, Kine Marita Knudsen; Nilsen, Jeannette; Sandlie, Inger; Andersen, Jan Terje

    2015-08-10

    Albumin is the most abundant protein in blood and acts as a molecular taxi for a plethora of small insoluble substances such as nutrients, hormones, metals and toxins. In addition, it binds a range of medical drugs. It has an unusually long serum half-life of almost 3weeks, and although the structure and function of albumin has been studied for decades, a biological explanation for the long half-life has been lacking. Now, recent research has unravelled that albumin-binding cellular receptors play key roles in the homeostatic regulation of albumin. Here, we review our current understanding of albumin homeostasis with a particular focus on the impact of the cellular receptors, namely the neonatal Fc receptor (FcRn) and the cubilin-megalin complex, and we discuss their importance on uses of albumin in drug delivery. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Stability of therapeutic albumin solutions used for molecular adsorbent recirculating system-based liver dialysis.

    PubMed

    De Bruyn, Tom; Meijers, Björn; Evenepoel, Pieter; Laub, Ruth; Willems, Ludo; Augustijns, Patrick; Annaert, Pieter

    2012-01-01

    Mounting evidence suggests beneficial effects of albumin dialysis-based liver support in patients suffering from acute-on-chronic liver failure. Molecular adsorbent recirculating system (MARS) is a nonbiological liver support device, based on the exchange of albumin-bound toxins between the patient's blood and a 20% human serum albumin solution in a secondary circuit. Bound toxins are continuously removed from the circulating albumin by exposure to activated charcoal and an ion-exchange resin. The aim of the present in vitro study was to determine the impact of exposure to charcoal and resin on the ligand binding properties of albumins, containing various levels of stabilizers and obtained from different suppliers (Baxter, CAF-DCF [Red Cross], and Sigma-Aldrich). Albumin binding properties were assessed by measuring equilibrium binding properties of warfarin, diazepam, and salicylate before and after incubation (for up to 7 h) with adsorbing materials; albumin-associated esterase-like activities were also determined. Notable changes in albumin binding upon incubation with adsorbing materials were only observed when using warfarin as a ligand. Affinity of warfarin for the Baxter and Sigma albumins showed a pronounced decrease (higher K(d) ) after the 1-7-h exposure to charcoal or resin. In the absence of adsorbing materials, similar effects were found, indicating that incubation time per se affects albumin binding properties. Following exposure to resin, Baxter albumin binding capacity (B(max)) increased about twofold. For albumin obtained from CAF-DCF, binding affinity and capacity for warfarin were constant under all conditions tested. Esterase-like activities associated with these albumins were either maintained or enhanced (up to 2.5-fold in case of Sigma albumin) following 7-h incubations with adsorbing materials. Our data suggest limited direct influence of the presence of stabilizers in therapeutic albumin solutions on baseline binding properties of human

  11. Study of influence of millimeter range electromagnetic waves on water-saline solutions of albumin

    NASA Astrophysics Data System (ADS)

    Shahinyan, Mariam A.; Antonyan, Ara P.; Mikaelyan, Marieta S.; Vardevanyan, Poghos O.

    2015-01-01

    In this work, the effect of electromagnetic waves of millimeter diapason (EMW MM) on both melting parameters of serum albumin from human blood and its solution density has been studied. It was shown that the irradiation of albumin solution results in protein denaturation at higher temperatures than in the case of nonirradiated samples, which indicates the increase of albumin packing degree. It was also shown that the enhancement of albumin solution density takes place which indicates the protein packing degree change as well. The obtained data show that the effect of EMW MM does not depend on frequency of these waves, because alterations are revealed at all studied frequencies — 41.8, 48 and 51.8GHz.

  12. Changes of protein solutions during storage: a study of albumin pharmaceutical preparations.

    PubMed

    Christiansen, Cathrine; Skotland, Tore

    2010-03-05

    During the production of air-filled albumin microspheres, to be used as an ultrasound contrast agent, it was observed that some albumin lots could not be used owing to albumin precipitation. In order to understand the reason for these lot-to-lot variations, 24 lots of 5% (w/v) human albumin pharmaceutical preparations were analysed. The results revealed that the good albumin lots all contained <0.03 mol of free SH groups per mol of albumin. The precipitation observed with other lots was most probably due to higher amounts of free SH groups. The lower amount of free SH groups in the good lots correlated with: (i) a yellow colour of the solutions and a UV-visible spectrum similar to that observed for non-enzymatic glycosylation; (ii) a decreased fructosamine content; (iii) an increased mobility against the anode in isoelectric focusing; and (iv) an increased truncation of the two N-terminal amino acids. No, or only small, differences were observed for the amounts of albumin dimer, albumin aggregates and protein impurities, and these could not account for the albumin precipitation. The differences observed between the albumin lots were most probably due to varying storage times and/or storage conditions, and incubation experiments revealed changes in all parameters that differed between the good and bad lots. Increasing the storage temperature or exposing the solutions to light resulted in a faster decrease of free SH groups and increase of the yellow colouration. It is likely that at least some of the changes observed were due to reactive degradation products formed from the stabilizer N-acetyl-L-tryptophan. The results presented should also be of interest regarding the storage of monoclonal antibodies and other proteins used in pharmaceuticals.

  13. Spectroscopic study on the interaction of pristine C60 and serum albumins in solution

    NASA Astrophysics Data System (ADS)

    Liu, Shufang; Sui, Yu; Guo, Kai; Yin, Zhijuan; Gao, Xibao

    2012-08-01

    The interaction of nanomaterials with biological macromolecules is an important foundation of the design and the biological safety assessments of nanomaterials. This work aims to investigate the interaction between pristine C60 and serum albumins (human serum albumin and bovine serum albumin) in solution. Stable aqueous dispersion of C60 was prepared by simple direct ultrasonic method and characterized by UV-vis spectrophotometry, transmission electronic microscopy and dynamic light scattering techniques, and spectroscopic methods (fluorescence spectroscopy, synchronous fluorescence spectroscopy and circular dichroism spectroscopy) were utilized for the investigation. It was found that the fluorescence of serum albumins could be quenched by C60 nanoparticles in a substantially similar way. Slight changes of the surrounding microenvironment of amino residues were observed, while little effects on the protein secondary structure occurred. The different effects of dispersion methods on the interaction of C60 nanoparticles with serum protein were also compared and discussed.

  14. Washing stored red blood cells in an albumin solution improves their morphological and hemorheological properties

    PubMed Central

    Reinhart, Walter H.; Piety, Nathaniel Z.; Deuel, Jeremy W.; Makhro, Asya; Schulzki, Thomas; Bogdanov, Nikolay; Goede, Jeroen S.; Bogdanova, Anna; Abidi, Rajaa; Shevkoplyas, Sergey S.

    2015-01-01

    BACKGROUND Prolonged storage of red blood cells leads to storage lesions, which may impair clinical outcomes after transfusion. A hallmark of storage lesions is progressive echinocytic shape transformation, which can be partially reversed by washing in albumin solutions. Here we have investigated the impact of this shape recovery on biorheological parameters. METHODS Red blood cells stored hypothermically for 6–7 weeks were washed in a 1% human serum albumin solution. Red cell deformability was measured with osmotic gradient ektacytometry. The viscosity of red cell suspensions were measured with a Couette-type viscometer. The flow behaviour of red cells suspended at 40% hematocrit was tested with an artificial microvascular network. RESULTS Washing in 1% albumin reduced higher degrees of echinocytes and increased the frequency of discocytes, thereby shifting the morphological index towards discocytosis. Washing also reduced red cell swelling. This shape recovery was not seen after washing in saline, buffer or plasma. Red cell shape normalisation did not improve cell deformability measured by ektacytometry, but it tended to decrease suspension viscosities at low shear rates and improved the perfusion of an artificial microvascular network. CONCLUSIONS Washing of stored red blood cells in a 1% human serum albumin solution specifically reduces echinocytosis, and this shape recovery has a beneficial effect on microvascular perfusion in vitro. Washing in 1% albumin may represent a new approach to improving the quality of stored red cells, and thus potentially reducing the likelihood of adverse clinical outcomes associated with transfusion of blood stored for longer periods of time. PMID:25752902

  15. Interaction of silicon nanoparticles with the molecules of bovine serum albumin in aqueous solutions

    SciTech Connect

    Anenkova, K A; Sergeeva, I A; Petrova, G P; Fedorova, K V; Osminkina, L A; Timoshenko, Viktor Yu

    2011-05-31

    Using the method of photon-correlation spectroscopy, the coefficient of translational diffusion D{sub t} and the hydrodynamic radius R of the particles in aqueous solutions of the bovine serum albumin, containing silicon nanoparticles, are determined. The character of the dependence of these parameters on the concentration of the protein indicates the absence of interaction between the studied particles in the chosen range of albumin concentrations 0.2 - 1.0 mg mL{sup -1}. (optical technologies in biophysics and medicine)

  16. Albumin holograms

    NASA Astrophysics Data System (ADS)

    Ordóñez-Padilla, M. J.; Olivares-Pérez, A.; Vega-Criollo, R.; Berriel-Valdos, L. R.; Mejias-Brizuela, N. Y.

    2011-02-01

    A Characterization is made with performance analysis of new photosensitive films of albumin to certain conditions for holographic recording based on interferometric array. We carried out the photo-oxidation of gallus gallus albumin albumin chemically combining powdered sugar (Glass ®) to an aqueous solution of ammonium dichromate. It was the analysis of the behavior of diffraction efficiency parameter through the intensity diffraction pattern produced by the gratings made with albumin.

  17. Arginine and lysine reduce the high viscosity of serum albumin solutions for pharmaceutical injection.

    PubMed

    Inoue, Naoto; Takai, Eisuke; Arakawa, Tsutomu; Shiraki, Kentaro

    2014-05-01

    Therapeutic protein solutions for subcutaneous injection must be very highly concentrated, which increases their viscosity through protein-protein interactions. However, maintaining a solution viscosity below 50 cP is important for the preparation and injection of therapeutic protein solutions. In this study, we examined the effect of various amino acids on the solution viscosity of very highly concentrated bovine serum albumin (BSA) and human serum albumin (HSA) at a physiological pH. Among the amino acids tested, l-arginine hydrochloride (ArgHCl) and l-lysine hydrochloride (LysHCl) (50-200 mM) successfully reduced the viscosity of both BSA and HSA solutions; guanidine hydrochloride (GdnHCl), NaCl, and other sodium salts were equally as effective, indicating the electrostatic shielding effect of these additives. Fourier transform infrared spectroscopy showed that BSA is in its native state even in the presence of ArgHCl, LysHCl, and NaCl at high protein concentrations. These results indicate that weakened protein-protein interactions play a key role in reducing solution viscosity. ArgHCl and LysHCl, which are also non-toxic compounds, will be used as additives to reduce the solution viscosity of concentrated therapeutic proteins.

  18. Where does the Albumin go? Human Albumin Solution usage following the implementation of a demand management programme.

    PubMed

    Yazdani, M S; Retter, A; Maggs, T; Li, P; Robson, M G; Reid, C; Holmes, P; Garood, T; Robinson, S E

    2017-06-01

    To outline the Guy's and St Thomas' NHS Foundation Trust (GSTFT) and Evelina London Children's Hospital (ELCH) demand management plan for human albumin solution (HAS) and usage. There is no UK-wide guidance governing the use of HAS. A severe shortage in 2015 prompted a Trust demand management programme. Indications were categorised according to locally agreed colour code and ASFA categories. Following the implementation of the demand management programme, a 6-month audit of HAS usage was completed. A total of 1303.1 L of HAS was used in 1139 infusions; 737 infusions were 20% HAS, accounting for 175.7 L (13.5%) in 181 patients. Indications for 20% HAS were red in 53.9% (94.7 L), blue in 26.5% (46.5 L) and grey in 19.6% (34.5 L). The remaining 1127.4 L (86.5%) infused were of 4.5 and 5 % HAS. A total of 1102.3 L (97.8%) was used for plasma exchange, 941.4 L (85.4%) ASFA category I, 93.7 L (8.5%) category II, 25.5 L (2.3%) category IV and 41.7 L (3.8%) for indications not specified according to ASFA; 25.1 L (2.2%) were used for a grey indication (volume resuscitation for hypovolaemia). The demand management programme provides surveillance of indications and retrospective verification of appropriate use. The majority of HAS indications were appropriate. Plasma exchange accounted for 84.6% of HAS usage and will be the focus of further demand management strategies. The demand management programme whilst aiming to promote best transfusion practice also ensures a tool to manage future shortages according to indication and available supply. © 2017 British Blood Transfusion Society.

  19. Posttranslational nitro-glycative modifications of albumin in Alzheimer's disease: implications in cytotoxicity and amyloid-β peptide aggregation.

    PubMed

    Ramos-Fernández, Eva; Tajes, Marta; Palomer, Ernest; Ill-Raga, Gerard; Bosch-Morató, Mònica; Guivernau, Biuse; Román-Dégano, Irene; Eraso-Pichot, Abel; Alcolea, Daniel; Fortea, Juan; Nuñez, Laura; Paez, Antonio; Alameda, Francesc; Fernández-Busquets, Xavier; Lleó, Alberto; Elosúa, Roberto; Boada, Mercé; Valverde, Miguel A; Muñoz, Francisco J

    2014-01-01

    Glycation and nitrotyrosination are pathological posttranslational modifications that make proteins prone to losing their physiological properties. Since both modifications are increased in Alzheimer's disease (AD) due to amyloid-β peptide (Aβ) accumulation, we have studied their effect on albumin, the most abundant protein in cerebrospinal fluid and blood. Brain and plasmatic levels of glycated and nitrated albumin were significantly higher in AD patients than in controls. In vitro turbidometry and electron microscopy analyses demonstrated that glycation and nitrotyrosination promote changes in albumin structure and biochemical properties. Glycated albumin was more resistant to proteolysis and less uptake by hepatoma cells occurred. Glycated albumin also reduced the osmolarity expected for a solution containing native albumin. Both glycation and nitrotyrosination turned albumin cytotoxic in a cell type-dependent manner for cerebral and vascular cells. Finally, of particular relevance to AD, these modified albumins were significantly less effective in avoiding Aβ aggregation than native albumin. In summary, nitrotyrosination and especially glycation alter albumin structural and biochemical properties, and these modifications might contribute for the progression of AD.

  20. Human serum albumin adsorption on TiO2 from single protein solutions and from plasma.

    PubMed

    Sousa, S R; Moradas-Ferreira, P; Saramago, B; Melo, L Viseu; Barbosa, M A

    2004-10-26

    In the present work, the adsorption of human serum albumin (HSA) on commercially pure titanium with a titanium oxide layer formed in a H(2)O(2) solution (TiO(2) cp) and on TiO(2) sputtered on Si (TiO(2) sp) was analyzed. Adsorption isotherms, kinetic studies, and work of adhesion determinations were carried out. HSA exchangeability was also evaluated. Surface characterization was performed by atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS), and wettability studies. The two TiO(2) surfaces have very distinct roughnesses, the TiO(2) sp having a mean R(a) value 14 times smaller than the one of TiO(2) cp. XPS analysis revealed consistent peaks representative of TiO(2) on sputtered samples as well as on Ti cp substrate after 48 h of H(2)O(2) immersion. Nitrogen was observed as soon as protein was present, while sulfur, present in disulfide bonds in HSA, was observed for concentrations of protein higher than 0.30 mg/mL. The work of adhesion was determined from contact angle measurements. As expected from the surface free energy values, the work of adhesion of HSA solution is higher for the TiO(2) cp substrate, the more hydrophilic one, and lower for the TiO(2) sp substrate, the more hydrophobic one. The work of adhesion between plasma and the substrates assumed even higher values for the TiO(2) cp surface, indicating a greater interaction between the surface and the complex protein solutions. Adsorption studies by radiolabeling of albumin ((125)I-HSA) suggest that rapid HSA adsorption takes place on both surfaces, reaching a maximum value after approximately 60 min of incubation. For the higher HSA concentrations in solution, a multilayer coverage was observed on both substrates. After the adsorption step from single HSA solutions, the exchangeability of adsorbed HSA molecules by HSA in solution was evaluated. The HSA molecules adsorbed on TiO(2) sp seem to be more easily exchanged by HSA itself than those adsorbed on TiO(2) cp after 24 h. In

  1. Intermolecular forces in bovine serum albumin solutions exhibiting solidlike mechanical behaviors.

    PubMed

    Ikeda, S; Nishinari, K

    2000-01-01

    Mechanical properties of bovine serum albumin (BSA) solutions were analyzed to gain information on intermolecular forces that stabilize the system under normal physiological conditions. BSA solutions showed unexpectedly large zero shear viscosity values under steady shear flows but responded like solids to sinusoidal linear strains: the storage shear moduli were always larger than the loss shear moduli in the frequency range 1-100 rad/s. These results suggest that BSA solutions are so-called colloidal crystals in which colloidal particles are ordered in an array due to strong repulsive forces among particles. However, the pair potential between BSA molecules predicted based on the conventional Derjaguin-Landau-Verwey-Overbeek theory failed to explain these remarkable mechanical properties of BSA solutions. Additional repulsive forces other than electrostatic must be introduced to explain stability of BSA aqueous dispersions.

  2. Comparison of human serum and bovine serum albumins on oxidation dynamics induced by talaporfin sodium photosensitization reaction with albumin rich conditions: solution experiments

    NASA Astrophysics Data System (ADS)

    Kurotsu, Mariko; Nakamura, Tetsuya; Takahashi, Mei; Ogawa, Emiyu; Arai, Tsunenori

    2014-02-01

    In order to understand extracellular-photosensitization reaction (PR) using talaporfin sodium, we studied comparison of oxidation dynamics of albumin and talaporfin sodium in solution system by visible and ultraviolet absorption spectrum measurements. Almost all talaporfin sodium particles may be bound to albumin in interstitial fluid, and this binding would affect the oxidation dynamics during this PR. Bovine serum albumin (BSA) is commonly used in vitro study but its binding characteristics with talaporfin sodium are different from human serum albumin (HSA). PR was operated in a solution composed of 20 μg/ml talaporfin sodium and 1.3 mg/ml HSA or BSA to simulate myocardial extracellular PR condition. Laser radiation of 662 nm was irradiated to this solution with irradiance of 0.29 W/cm2. Absorption spectra of these solutions were measured during the PR. We estimated oxidized ratio by absorption difference around 240 nm before and after the PR. Talaporfin sodium was oxidized 100% with HSA and BSA by the PR of 100 J/cm2 in radiant exposure. On the other hand, HSA and BSA were oxidized 60% and 94%, respectively in this radiant exposure. Q-band absorption peak of talaporfin sodium with HSA was shifted to 1 nm longer wavelength increasing radiant exposure up to 100 J/cm2. This longer wavelength shift would mean binding ratio of non-oxidized talaporfin sodium to non-oxidized HSA was increased with increasing radiant exposure. Therefore it would be possible that PR with talaporfin sodium bound to HSA might present efficient PDT than PR bound to BSA.

  3. Facilitated Diffusion and Membrane Permeation of Fatty Acid in Albumin Solutions

    PubMed Central

    Barta, Efrath; Sideman, Samuel; Bassingthwaighte, James B.

    2010-01-01

    Facilitated transport is characteristic of most living systems, and usually involves a series of consecutive adjacent transfer regions, each having different transport properties. As a first step in the analysis of the multiregional problem, we consider in a single unstirred layer the facilitated diffusion of fatty acid (F) in albumin (A) solution under conditions of slow versus rapid association–dissociation, accounting for differing diffusivities of the albumin-fatty acid complex (AF). Diffusion gradients become established in an unstirred layer between a source of constant concentration of A, AF, and F in equilibrium, and a membrane permeable to F. The posited system does not reduce to a thin- or thick-layer approximation. The transient state is prolonged by slower on/off binding rates and by increasing the thickness of the unstirred layer. Solutions to transient and steady state depend the choice of boundary conditions, especially upon for thin regions. When there are two regions (each with its specific binding protein) separated by a permeable membrane, the steady-state fluxes and concentration profiles depend on the rates of association and dissociation reactions, on the diffusion coefficients, local consumption rates, and on the membrane permeability. Sensitivity analysis reveals the relative importance of these mechanisms. PMID:10784097

  4. Self-assembling of poly(aspartic acid) with bovine serum albumin in aqueous solutions.

    PubMed

    Nita, L E; Chiriac, A P; Bercea, M; Asandulesa, M; Wolf, Bernhard A

    2017-02-01

    Macromolecular co-assemblies built up in aqueous solutions, by using a linear polypeptide, poly(aspartic acid) (PAS), and a globular protein, bovine serum albumin (BSA), have been studied. The main interest was to identify the optimum conditions for an interpenetrated complex formation in order to design materials suitable for biomedical applications, such as drug delivery systems. BSA surface possesses several amino- and carboxylic groups available for covalent modification, and/or bioactive substances attachment. In the present study, mixtures between PAS and BSA were investigated at 37°C in dilute aqueous solution by viscometry, dynamic light scattering and zeta potential determination, as well as in solid state by AFM microscopy and dielectric spectroscopy. The experimental data have shown that the interpolymer complex formation occurs for a PAS/BSA molar ratio around 0.541.

  5. The conformation of serum albumin in solution: a combined phosphorescence depolarization-hydrodynamic modeling study.

    PubMed Central

    Ferrer, M L; Duchowicz, R; Carrasco, B; de la Torre, J G; Acuña, A U

    2001-01-01

    There is a striking disparity between the heart-shaped structure of human serum albumin (HSA) observed in single crystals and the elongated ellipsoid model used for decades to interpret the protein solution hydrodynamics at neutral pH. These two contrasting views could be reconciled if the protein were flexible enough to change its conformation in solution from that found in the crystal. To investigate this possibility we recorded the rotational motions in real time of an erythrosin-bovine serum albumin complex (Er-BSA) over an extended time range, using phosphorescence depolarization techniques. These measurements are consistent with the absence of independent motions of large protein segments in solution, in the time range from nanoseconds to fractions of milliseconds, and give a single rotational correlation time phi(BSA, 1 cP, 20 degrees C) = 40 +/- 2 ns. In addition, we report a detailed analysis of the protein hydrodynamics based on two bead-modeling methods. In the first, BSA was modeled as a triangular prismatic shell with optimized dimensions of 84 x 84 x 84 x 31.5 A, whereas in the second, the atomic-level structure of HSA obtained from crystallographic data was used to build a much more refined rough-shell model. In both cases, the predicted and experimental rotational diffusion rate and other hydrodynamic parameters were in good agreement. Therefore, the overall conformation in neutral solution of BSA, as of HSA, should be rigid, in the sense indicated above, and very similar to the heart-shaped structure observed in HSA crystals. PMID:11325741

  6. Conformational changes in human serum albumin induced by sodium perfluorooctanoate in aqueous solutions.

    PubMed

    Messina, Paula V; Prieto, Gerardo; Ruso, Juan M; Sarmiento, Félix

    2005-08-18

    Conformational changes in the bulk solution and at the air-aqueous interface of human serum albumin (HSA) induced by changes in concentration of sodium perfluorooctanoate (C(7)F(15)COO(-)Na(+)) were studied by difference spectroscopy, zeta-potential data, and axisymmetric drop shape analysis. zeta-potential was used to monitor the formation of the HSA-C(7)F(15)COO(-)Na(+) complex and the surface charge of the complex. The conformational transition of HSA in the bulk solution was followed as a function of denaturant concentration by absorbance measurements at 280 nm. The data were analyzed to obtain values for the Gibbs energies of the transition in water (DeltaG(0)(W)) and in a hydrophobic environment (DeltaG(0)(hc)) pertaining to saturated protein-surfactant complexes. The conformational changes that surfactants induce in HSA molecules alter its absorption behavior at the air-water interface. Dynamic surface measurements were used to evaluate this behavior. At low [C(7)F(15)COO(-)Na(+)], proteins present three adsorption regimes: induction time, monolayer saturation, and interfacial gelation. When surfactant concentration increases and conformational changes in the bulk solution occur, the adsorption regimes disappear. HSA molecules in an intermediate conformational state migrate to the air-water interface and form a unique monolayer. At high [C(7)F(15)COO(-)Na(+)], the adsorption of denatured molecules exhibits a behavior analogous to that of dilute solutions.

  7. Experience of using human albumin solution 4.5% in 1195 therapeutic plasma exchange procedures.

    PubMed

    Pusey, C; Dash, C; Garrett, M; Gascoigne, E; Gesinde, M; Gillanders, K; Wallington, T

    2010-08-01

    The aim of the study was to document the incidence of adverse reactions (ADRs) in subjects undergoing therapeutic plasma exchange with human albumin 4.5% solution (Zenalb 4.5) and to explore whether there were any differences in tolerability with a change from UK to US plasma and a subsequent manufacturing modification. Zenalb 4.5 was initially manufactured from recovered plasma from UK blood donations and later from source plasma from US donors. The modification was a salt diafiltration step. A prospective survey was conducted at three UK aphaeresis units; data from 154 subjects undergoing 1195 plasma exchanges using Zenalb 4.5 were collected. Adverse events with at least a possible relationship to treatment were recorded. There were 20 ADRs per 1195 exchanges (1.7%), experienced by 14 subjects (9.1%). The most common reaction was rigours in 17 exchanges (1.4%) and 12 subjects (7.8%). ADRs occurred in 0.8% (2/250) of plasma exchanges with UK plasma, 0.2% (1/539) using US plasma/original manufacturing method, 4.3% (16/370) using US plasma/modified method and 12.5% (1/8) using US plasma/mixed original and modified methods. Data were incomplete for the remaining 28 exchanges, but no ADRs were reported. Moreover, 17 ADRs occurred over a 14-month period and involved 10 batches manufactured from US plasma (1 original, 9 by modified method). The incidence then returned to the previously lower level. There was no explanation for this cluster of events. Overall, there was no evidence that plasma source or manufacturing method affected tolerability and it was concluded that human albumin 4.5% solution (Zenalb 4.5) is well tolerated during plasma exchange therapy.

  8. DNP-Enhanced MAS NMR of Bovine Serum Albumin Sediments and Solutions

    PubMed Central

    2015-01-01

    Protein sedimentation sans cryoprotection is a new approach to magic angle spinning (MAS) and dynamic nuclear polarization (DNP) nuclear magnetic resonance (NMR) spectroscopy of proteins. It increases the sensitivity of the experiments by a factor of ∼4.5 in comparison to the conventional DNP sample preparation and circumvents intense background signals from the cryoprotectant. In this paper, we investigate sedimented samples and concentrated frozen solutions of natural abundance bovine serum albumin (BSA) in the absence of a glycerol-based cryoprotectant. We observe DNP signal enhancements of ε ∼ 66 at 140 GHz in a BSA pellet sedimented from an aqueous solution containing the biradical polarizing agent TOTAPOL and compare this with samples prepared using the conventional protocol (i.e., dissolution of BSA in a glycerol/water cryoprotecting mixture). The dependence of DNP parameters on the radical concentration points to the presence of an interaction between TOTAPOL and BSA, so much so that a frozen solution sans cryoprotectant still gives ε ∼ 50. We have studied the interaction of BSA with another biradical, SPIROPOL, that is more rigid than TOTAPOL and has been reported to give higher enhancements. SPIROPOL was also found to interact with BSA, and to give ε ∼ 26 close to its maximum achievable concentration. Under the same conditions, TOTAPOL gives ε ∼ 31, suggesting a lesser affinity of BSA for SPIROPOL with respect to TOTAPOL. Altogether, these results demonstrate that DNP is feasible in self-cryoprotecting samples. PMID:24460530

  9. DNP-enhanced MAS NMR of bovine serum albumin sediments and solutions.

    PubMed

    Ravera, Enrico; Corzilius, Björn; Michaelis, Vladimir K; Luchinat, Claudio; Griffin, Robert G; Bertini, Ivano

    2014-03-20

    Protein sedimentation sans cryoprotection is a new approach to magic angle spinning (MAS) and dynamic nuclear polarization (DNP) nuclear magnetic resonance (NMR) spectroscopy of proteins. It increases the sensitivity of the experiments by a factor of ∼4.5 in comparison to the conventional DNP sample preparation and circumvents intense background signals from the cryoprotectant. In this paper, we investigate sedimented samples and concentrated frozen solutions of natural abundance bovine serum albumin (BSA) in the absence of a glycerol-based cryoprotectant. We observe DNP signal enhancements of ε ∼ 66 at 140 GHz in a BSA pellet sedimented from an aqueous solution containing the biradical polarizing agent TOTAPOL and compare this with samples prepared using the conventional protocol (i.e., dissolution of BSA in a glycerol/water cryoprotecting mixture). The dependence of DNP parameters on the radical concentration points to the presence of an interaction between TOTAPOL and BSA, so much so that a frozen solution sans cryoprotectant still gives ε ∼ 50. We have studied the interaction of BSA with another biradical, SPIROPOL, that is more rigid than TOTAPOL and has been reported to give higher enhancements. SPIROPOL was also found to interact with BSA, and to give ε ∼ 26 close to its maximum achievable concentration. Under the same conditions, TOTAPOL gives ε ∼ 31, suggesting a lesser affinity of BSA for SPIROPOL with respect to TOTAPOL. Altogether, these results demonstrate that DNP is feasible in self-cryoprotecting samples.

  10. UW solution improved with high anti-apoptotic activity by S-nitrosated human serum albumin.

    PubMed

    Ishima, Yu; Shinagawa, Takuya; Yoneshige, Shinji; Kragh-Hansen, Ulrich; Ohya, Yuki; Inomata, Yukihiro; Kai, Toshiya; Otagiri, Masaki; Maruyama, Toru

    2013-04-01

    S-Nitrosated human serum albumin (SNO-HSA) is useful in preventing liver ischemia/reperfusion injury, and SNO-HSA should thus be able to prevent cell injury during liver transplantation. However, the potential protective effect of SNO-HSA on a combination of cold and warm ischemia, which is obligatory when performing liver transplantation, has not been examined. Therefore, we evaluated the protective effect of SNO-HSA added to University of Wisconsin (UW) solution during cold or/and warm ischemia in situ and in vitro. First, we observed that apoptotic and necrotic cell death were increased during cold and warm ischemia, respectively. SNO-HSA, which possesses anti-apoptosis activity at low NO concentrations, can inhibit cold ischemia injury both in situ and in vitro. In contrast, SNO-HSA had no significant effect on warm liver ischemia injury which, however, can be reduced by UW solution. We also demonstrated that the cellular uptake of NO from SNO-HSA can occur during cold ischemia resulting in induction of heme oxygenase-1 within 3h of cold ischemia. Our results indicate that treatment with SNO-HSA or UW solution alone is not sufficient to inhibit liver injury during a period of both cold and warm ischemia. However, a combination of SNO-HSA and UW solution can be used to prevent the two types of ischemia. SNO-HSA-added UW solution could be very useful in transplantation, because the previously imposed constraints on preservation time can be removed. This is a great advantage in a situation as the present one with increased utilization of scarce donor organs for more recipients.

  11. Albumin versus crystalloid prime solution for cardiopulmonary bypass in young children.

    PubMed

    Riegger, Lori Q; Voepel-Lewis, Terri; Kulik, Thomas J; Malviya, Shobha; Tait, Alan R; Mosca, Ralph S; Bove, Edward L

    2002-12-01

    To determine the effects of adding 5% albumin to the cardiopulmonary bypass prime on perioperative fluid status and fluid management in young children. Prospective randomized study. Single university hospital. Pediatric patients of <14 kg undergoing cardiac surgery requiring cardiopulmonary bypass. Patients received a 5% albumin prime or a crystalloid prime. Perioperative fluid intake, output, and daily weights were recorded. Serial hematocrits, colloid osmotic pressures, and serum albumins were measured. Outcomes and complications were documented. There were 86 patients aged 3 days to 4 yrs; 44 patients had an albumin prime and 42 had a crystalloid prime. Patients in the albumin group had a net negative fluid balance at the end of cardiopulmonary bypass compared with a net positive fluid balance in the crystalloid group. Patients in the albumin group had significantly higher serum albumins and colloid osmotic pressures and gained less weight postoperatively. However, their hematocrits were lower, and more patients in the albumin group received packed red blood cells. By 24 hrs postoperatively, there were no differences in colloid osmotic pressures and hematocrits between groups, and by the fourth postoperative day, there was no difference in weight gain. No differences were found in length of mechanical ventilation, intensive care unit or hospital stay, complications, or mortality. Albumin in the prime may attenuate the extravasation of fluid out of the vascular space, but it may be associated with an increased transfusion rate. The risk/benefit ratio for this intervention warrants further study.

  12. Thermomechanical effects of co-solute on the structure formation of bovine serum albumin.

    PubMed

    George, Paul; Lundin, Leif; Kasapis, Stefan

    2014-08-15

    The effect of glucose syrup on the structural properties of bovine serum albumin has been addressed in preparations from low to high solids. Fifteen percent protein was mixed with the co-solute at concentrations up to 65% and subjected to thermal treatment to examine the changes in phase and state transitions. Thermomechanics were the working protocol being carried out with micro differential scanning calorimetry and small deformation dynamic oscillation. Results argue that protein molecules have been extensively stabilised by the addition of a co-solute, recorded via a delayed thermal denaturation. Further, increasing the glucose syrup enhanced polymer-polymer interactions leading to stronger networks following thermal denaturation of the globular protein. Condensed BSA/glucose syrup mixtures, i.e. at 80% solids, were cooled at subzero temperatures to exhibit a considerable state of vitrification. Molecular relaxation phenomena were successfully followed using theoretical concepts from synthetic polymer research to yield the mechanical glass transition temperature. Copyright © 2014. Published by Elsevier Ltd.

  13. Study of the interaction of C60 fullerene with human serum albumin in aqueous solution

    SciTech Connect

    Li, Song; Zhao, Xiongce; Mo, Yiming; Cummings, Peter T; Heller, William T

    2013-01-01

    Concern about the toxicity of engineered nanoparticles, such as the prototypical nanomaterial C60 fullerene, continues to grow. While evidence continues to mount that C60 and its derivatives may pose health hazards, the specific molecular interactions of these particles with biological macromolecules require further investigation. To better understand the interaction of C60 with proteins, the protein human serum albumin (HSA) was studied in solution with C60 at C60:HSA molar ratios ranging from 1:2 to 4:1. HSA is the major protein component of blood plasma and plays a role in a variety of functions, such as the maintenance of blood pH and pressure. The C60-HSA interaction was probed by a combination of circular dichroism (CD) spectroscopy, small-angle neutron scattering (SANS) and atomistic molecular dynamics (MD) simulations to understand C60-driven changes in the structure of HSA in solution. The CD spectroscopy demonstrates that the secondary structure of the protein decreases in -helical content in response to the presence of C60. Similarly, C60 produces subtle changes in the solution conformation of HSA, as evidenced by the SANS data and MD. The data do not indicate that C60 is causing a change in the oligomerization state of the protein. Taken together results demonstrate that C60 interacts with HSA, but it does not strongly perturb the structure of the protein by unfolding it or inducing aggregation, suggesting a mechanism for transporting C60 throughout the body to accumulate in various tissues.

  14. Spectral-luminescent study of the interaction of some styrylcyanine dyes with bovine serum albumin and DNA in aqueous solutions

    NASA Astrophysics Data System (ADS)

    Nizomov, Negmat; Kurtaliev, Eldar N.; Nizamov, Shawkat N.; Khodjayev, Gayrat

    2009-11-01

    Spectral-luminescent characteristics of the several new styrylcyanine dyes, synthesized on the base of F dye ((E)-4-(4-(dimethylamino)styryl)-1-methylpyridinium iodide), were studied in aqueous solutions in the presence and absence of bovine serum albumin and deoxyribonucleic acid. It was shown, that with the rise of concentration of bovine serum albumin and deoxyribonucleic acid in aqueous solution, the bathochromic shift of electronic absorption spectra band and sharp intensity increase of fluorescence band intensity are observed for studied dyes, while the shape of absorption and fluorescence bands remains intact. Biophysical parameters (the binding constant and quantity of the binding sites) of interaction of studied dyes with BSA and DNA were determined. It is shown, that homodimer styrylcyanine dyes with a pentyl - or longer linking chain have larger binding affinity to specified biomolecules than dyes with shorter link-chain.

  15. Broadband measurements of the frequency dependence of attenuation coefficient and velocity in amniotic fluid, urine and human serum albumin solutions.

    PubMed

    Verma, Prashant K; Humphrey, Victor F; Duck, Francis A

    2005-10-01

    The frequency dependence of attenuation coefficient in amniotic fluid, urine and 4.5% and 20% human serum albumin solutions over the frequency range 5 MHz to 25 MHz was measured at both room temperature and physiological temperature using a variable path length technique. A 15 MHz (13 mm diameter) transducer was used to produce a broadband single-cycle pulse and a 4 mm diameter bilaminar polyvinylidene difluoride membrane hydrophone was used to detect the attenuated pulse. Standard time-of-flight measurement techniques were used to measure the acoustic velocity in the same fluid samples. At physiological temperature, the attenuation coefficients in amniotic fluid, urine and 4.5% and 20% human albumin solution were found to be 0.0053 f(1.65), 0.0047 f(1.67), 0.019 f(1.57) and 0.167 f(1.27) dB cm(-1), respectively, where f is in MHz. The velocities in amniotic fluid, urine and 4.5% human albumin solution at physiological temperature were found to be 1541.1 m s(-1) +/- 1.3 m s(-1), 1551.3 m s(-1) +/- 1.3 ms(-1) and 1547.3 m s(-1) +/- 1.0 m s(-1), respectively. The results provide unique data over the diagnostic and therapeutic ultrasonic frequency range that can be used as input data for theoretical models that attempt to simulate nonlinear pressure fields and temperature rises from medical ultrasonic transducers.

  16. A 'turn-on' fluorescent chemosensor for quantification of serum albumin in aqueous solution at neutral pH.

    PubMed

    Li, Yuanyuan; Li, Kai; He, Juan

    2016-05-01

    A fluorescent chemosensor 1 (4-diethylamino-2'-hydroxychalcone) for detecting serum albumin with long-wavelength emission, good selectivity and facile synthesis was reported. Upon the addition of bovine serum albumin (BSA) to an aqueous solution of 1 at neutral pH, a 'turn-on' fluorescence response was observed at 596 nm based on a hydrophobic binding mode between 1 and BSA. A linear range of 0.10-1.00 mg/mL and a detection limit of 9.1 µg/mL for BSA were obtained, respectively. Moreover, 1 was successfully applied to detect BSA in real bovine serum samples with satisfied recovery and accuracy, which suggested that 1 could serve as a valid and effective fluorescent chemosensor for quantification of BSA. Copyright © 2015 John Wiley & Sons, Ltd.

  17. Assessment of chemical exchange in tryptophan-albumin solution through (19)F multicomponent transverse relaxation dispersion analysis.

    PubMed

    Lin, Ping-Chang

    2015-06-01

    A number of NMR methods possess the capability of probing chemical exchange dynamics in solution. However, certain drawbacks limit the applications of these NMR approaches, particularly, to a complex system. Here, we propose a procedure that integrates the regularized nonnegative least squares (NNLS) analysis of multiexponential T2 relaxation into Carr-Purcell-Meiboom-Gill (CPMG) relaxation dispersion experiments to probe chemical exchange in a multicompartmental system. The proposed procedure was validated through analysis of (19)F T2 relaxation data of 6-fluoro-DL-tryptophan in a two-compartment solution with and without bovine serum albumin. Given the regularized NNLS analysis of a T2 relaxation curve acquired, for example, at the CPMG frequency υ CPMG  = 125, the nature of two distinct peaks in the associated T2 distribution spectrum indicated 6-fluoro-DL-tryptophan either retaining the free state, with geometric mean */multiplicative standard deviation (MSD) = 1851.2 ms */1.51, or undergoing free/albumin-bound interconversion, with geometric mean */MSD = 236.8 ms */1.54, in the two-compartment system. Quantities of the individual tryptophan species were accurately reflected by the associated T2 peak areas, with an interconversion state-to-free state ratio of 0.45 ± 0.11. Furthermore, the CPMG relaxation dispersion analysis estimated the exchange rate between the free and albumin-bound states in this fluorinated tryptophan analog and the corresponding dissociation constant of the fluorinated tryptophan-albumin complex in the chemical-exchanging, two-compartment system.

  18. Catalysis of S-nitrosothiols formation by serum albumin: The mechanism and implication in vascular control

    PubMed Central

    Rafikova, Olga; Rafikov, Ruslan; Nudler, Evgeny

    2002-01-01

    Nitric oxide (NO⋅) is a short-lived physiological messenger. Its various biological activities can be preserved in a more stable form of S-nitrosothiols (RS-NO). Here we demonstrate that at physiological NO⋅ concentrations, plasma albumin becomes saturated with NO⋅ and accelerates formation of low-molecular-weight (LMW) RS-NO in vitro and in vivo. The mechanism involves micellar catalysis of NO⋅ oxidation in the albumin hydrophobic core and specific transfer of NO+ to LMW thiols. Albumin-mediated S-nitrosylation and its vasodilatory effect directly depend on the concentration of circulating LMW thiols. Results suggest that the hydrophobic phase formed by albumin serves as a major reservoir of NO⋅ and its reactive oxides and controls the dynamics of NO⋅-dependant processes in the vasculature. PMID:11983891

  19. Induction of Neuronal Death by Microglial AGE-Albumin: Implications for Alzheimer’s Disease

    PubMed Central

    Byun, Kyunghee; Bayarsaikhan, Enkhjaigal; Kim, Daesik; Kim, Chae Young; Mook-Jung, Inhee; Paek, Sun Ha; Kim, Seung U.; Yamamoto, Tadashi; Won, Moo-Ho; Song, Byoung-Joon; Park, Young Mok; Lee, Bonghee

    2012-01-01

    Advanced glycation end products (AGEs) have long been considered as potent molecules promoting neuronal cell death and contributing to neurodegenerative disorders such as Alzheimer’s disease (AD). In this study, we demonstrate that AGE-albumin, the most abundant AGE product in human AD brains, is synthesized in activated microglial cells and secreted into the extracellular space. The rate of AGE-albumin synthesis in human microglial cells is markedly increased by amyloid-β exposure and oxidative stress. Exogenous AGE-albumin upregulates the receptor protein for AGE (RAGE) and augments calcium influx, leading to apoptosis of human primary neurons. In animal experiments, soluble RAGE (sRAGE), pyridoxamine or ALT-711 prevented Aβ-induced neuronal death in rat brains. Collectively, these results provide evidence for a new mechanism by which microglial cells promote death of neuronal cells through synthesis and secretion of AGE-albumin, thereby likely contributing to neurodegenerative diseases such as AD. PMID:22662249

  20. The albumin controversy.

    PubMed

    Uhing, Michael R

    2004-09-01

    There are relatively few studies of albumin use in neonates and children, with most showing no consistent benefit compared with the use of crystalloid solutions. Certainly, albumin treatment is not indicated for treatment of hypoalbuminemia alone. Studies also show that albumin is not indicated in neonates for the initial treatment of hypotension, respiratory distress, or partial exchange transfusions. In adults, albumin is not considered to be the initial therapy for hypovolemia, burn injury, or nutritional supplementation. Based on the evidence, albumin should be used rarely in the neonatal ICU. Albumin may be indicated in the treatment of hypovolemia only after crystalloid infusion has failed. In patients with acute hemorrhagic shock, albumin may be used with crystalloids when blood products are not available immediately. Inpatients with acute or continuing losses of albumin and normal capillary permeability and lymphatic function, such as during persistent thoracostomy tube or surgical site drainage, albumin supplementation will prevent the development of hypoalbuminemia, and possibly edema formation. This has not been studied systematically, however. In patients with hypoalbuminemia and increased capillary permeability, albumin supplementation often leads to greater albumin leakage across the capillary membrane, contributing to edema formation without improvement in outcome. As the disease process improves and capillary permeability normalizes, albumin supplementation may accelerate recovery, but long-term benefits of albumin treatment usually cannot be demonstrated. These patients will recover whether or not albumin is administered.

  1. Metal-catalyzed oxidation of human serum albumin: conformational and functional changes. Implications in protein aging.

    PubMed

    Meucci, E; Mordente, A; Martorana, G E

    1991-03-15

    Mild oxidative stress, as elicited by ascorbate, oxygen, and trace metals, affects the binding properties of human serum albumin via purely conformational changes. In fact, no gross alteration can be observed in the electrophoretic and chromatographic patterns of albumin, whereas localized modifications are indicated by the changes in absorption and fluorescence spectra and in polarization degree. The oxidized protein presents a small increase of bityrosine production and a time-dependent increase in the content of carbonyl groups, whereas proteolytic susceptibility is unchanged. A higher affinity for cis-parinaric acid and a slight loss of solubility in high salt indicate a greater surface hydrophobicity. Pinpoint denaturation of the albumin molecule is also suggested by a decreased "esterase" activity in the presence of p-nitrophenyl acetate. Conformational stability evaluated through thermal shock and addition of moderate amounts of guanidine indicate that the oxidized protein is more heat-resistant, less flexible, and more rigid than the native one. Although limited, structural damages afforded by the oxidative stress cause alterations of albumin binding properties as documented by experiments with probes and physiological ligands. The loss of biological activity of human serum albumin induced by ascorbate system appears of medical relevance, because it can affect drug metabolism and particularly drug tolerance in the elderly.

  2. The effect of methylamine on the solution structures of human and bovine serum albumins

    NASA Astrophysics Data System (ADS)

    Hamdani, S.; Joly, D.; Carpentier, R.; Tajmir-Riahi, H. A.

    2009-11-01

    Serum albumins are the major soluble protein constituents of the circulatory system and have many physiological functions including transporting a variety of compounds. Methylamine, a monoamine with one positive charge complexes with protein and alters protein secondary structure. The aim of this study was to examine the interactions of human serum albumin (HSA) and bovine serum albumin (BSA) with methylamine at physiological conditions, using constant protein concentration and various monoamine concentrations. FTIR, UV-vis, CD and fluorescence spectroscopic methods were used to analyse methylamine binding mode, the binding constant and the effects of monoamine on HSA and BSA stability and conformations. Structural analysis showed that methylamine binds HSA and BSA via hydrophilic (polypeptide and amine polar groups) and hydrophobic interactions with overall binding constants of Kmet-HSA = 2.42 (±0.5) × 10 2 M -1 and Kmet-BSA = 1.34 (±0.3) × 10 3 M -1 with the number of bound methylamine around one molecule per protein. Methylamine complexation alters protein conformation by major reduction of α-helix and increase in random coil and turn structures indicating a partial protein unfolding.

  3. Redox balance mechanisms in Schistosoma mansoni rely on peroxiredoxins and albumin and implicate peroxiredoxins as novel drug targets.

    PubMed

    Sayed, Ahmed A; Cook, Shawna K; Williams, David L

    2006-06-23

    Schistosoma mansoni, a causative agent of schistosomiasis, resides in the hepatic portal circulation of their human host up to 30 years without being eliminated by the host immune attack. Production of an antioxidant "firewall," which would neutralize the oxidative assault generated by host immune defenses, is one proposed survival mechanism of the parasite. Schistosomes lack catalase, the main H2O2-neutralizing enzyme of many organisms, and their glutathione peroxidases are in the phospholipid class with poor reactivity toward H2O2. Evidence implicates peroxiredoxins (Prx) as providing the main enzymatic activity to reduce H2O2 in the parasite. Quantitative monitoring of Prx mRNAs during parasite life cycle indicated that Prx proteins are differentially expressed, with highest expression occurring in adult stages (oxidative resistant stages). Incubation of schistosomula with Prx1 double-stranded RNA knocked down total Prx enzymatic activity and resulted in lowered survival of cultured parasites compared with controls demonstrating that Prx are essential parasite proteins. These results represent the first report of lethal gene silencing in Schistosoma. Investigation of downstream effects of Prx silencing revealed an abrupt increase of lipid peroxides and the generation of several oxidized proteins. Using mass spectrometry, parasite albumin and actin were identified as the main oxidized proteins. Gene expression analysis showed that schistosome albumin was induced by oxidative stress. This study highlights Prx proteins as essential parasite proteins and potential new targets for anti-schistosome drug development and albumin as a novel, sacrificial oxidant scavenging protein in parasite redox regulation.

  4. Chicken serum albumin (Gal d 5*) is a partially heat-labile inhalant and food allergen implicated in the bird-egg syndrome.

    PubMed

    Quirce, S; Marañón, F; Umpiérrez, A; de las Heras, M; Fernández-Caldas, E; Sastre, J

    2001-08-01

    Chicken serum albumin (alpha-livetin) has been implicated as the causative allergen of the bird-egg syndrome. However, the clinical relevance of sensitization to this allergen has not been confirmed by specific challenge tests and environmental sampling. We investigated whether chicken albumin can be detected in air samples collected in a home with birds, and whether sensitization to this protein may cause respiratory and food allergy symptoms. The heat resistance of chicken albumin and the possible cross-reactivity with conalbumin were also investigated. We studied eight patients with food allergy to egg yolk who also suffered from respiratory symptoms (rhinitis and/or asthma) caused by exposure to birds. Sensitization to egg yolk and bird antigens was investigated by skin and serologic tests. Hypersensitivity to chicken albumin was confirmed by specific bronchial, conjunctival, and oral provocation tests. All patients had positive skin tests and serum IgE against egg yolk, chicken serum, chicken meat, bird feathers, and chicken albumin. The presence of airborne chicken albumin in the domestic environment was confirmed. Specific bronchial challenge to chicken albumin elicited early asthmatic responses in six patients with asthma. An oral challenge with chicken albumin provoked digestive and systemic allergic symptoms in the two patients challenged. IgE reactivity to chicken albumin was reduced by 88% after heating at 90 degrees C for 30 min. ELISA inhibition demonstrated only partial cross-reactivity between chicken albumin and conalbumin. Chicken albumin (Gal d 5) is a partially heat-labile allergen that may cause both respiratory and food-allergy symptoms in patients with the bird-egg syndrome.

  5. Hemoglobin inhibits albumin uptake by proximal tubule cells: implications for sickle cell disease.

    PubMed

    Eshbach, Megan L; Kaur, Amandeep; Rbaibi, Youssef; Tejero, Jesús; Weisz, Ora A

    2017-06-01

    Proximal tubule (PT) dysfunction, including tubular proteinuria, is a significant complication in young sickle cell disease (SCD) that can eventually lead to chronic kidney disease. Hemoglobin (Hb) dimers released from red blood cells upon hemolysis are filtered into the kidney and internalized by megalin/cubilin receptors into PT cells. The PT is especially sensitive to heme toxicity, and tubular dysfunction in SCD is thought to result from prolonged exposure to filtered Hb. Here we show that concentrations of Hb predicted to enter the tubule lumen during hemolytic crisis competitively inhibit the uptake of another megalin/cubilin ligand (albumin) by PT cells. These effects were independent of heme reduction state. The Glu7Val mutant of Hb that causes SCD was equally effective at inhibiting albumin uptake compared with wild-type Hb. Addition of the Hb scavenger haptoglobin (Hpt) restored albumin uptake in the presence of Hb, suggesting that Hpt binding to the Hb αβ dimer-dimer interface interferes with Hb binding to megalin/cubilin. BLAST searches and structural modeling analyses revealed regions of similarity between Hb and albumin that map to this region and may represent sites of Hb interaction with megalin/cubilin. Our studies suggest that impaired endocytosis of megalin/cubilin ligands, rather than heme toxicity, may be the cause of tubular proteinuria in SCD patients. Additionally, loss of these filtered proteins into the urine may contribute to the extra-renal pathogenesis of SCD. Copyright © 2017 the American Physiological Society.

  6. Radiation-induced chemical transformations of human serum albumin in aqueous solutions

    SciTech Connect

    Kondakova, N.V.; Ripa, N.V.; Kuznetsova, N.V.

    1994-11-01

    A rate constant of the reaction of human serum albumin (HSA) with OH radicals was determined using the method of competing scavengers. Changes in the amino acid composition and some biochemical properties of HSA on radiolysis in a borate buffer (pH 7.4) saturated with N{sub 2}O or O{sub 2} were correlated quantitatively. It was found that the yield of peptide bonds that lost the ability to be cleaved by trypsin is higher than the total yield of arginine and lysine residues in HSA. The possibility of accumulation of modified HSA in blood upon irradiation was considered.

  7. Human albumin solution for patients with cirrhosis and acute on chronic liver failure: Beyond simple volume expansion

    PubMed Central

    Valerio, Christopher; Theocharidou, Eleni; Davenport, Andrew; Agarwal, Banwari

    2016-01-01

    To provide an overview of the properties of human serum albumin (HSA), and to review the evidence for the use of human albumin solution (HAS) in critical illness, sepsis and cirrhosis. A MEDLINE search was performed using the terms “human albumin”, “critical illness”, “sepsis” and “cirrhosis”. The references of retrieved articles were reviewed manually. Studies published between 1980 and 2014 were selected based on quality criteria. Data extraction was performed by all authors. HSA is the main plasma protein contributing greatly to its oncotic pressure. HSA demonstrates important binding properties for endogenous and exogenous toxins, drugs and drug metabolites that account for its anti-oxidant and anti-inflammatory properties. In disease states, hypoalbuminaemia is secondary to decreased HSA production, increased loss or transcapillary leakage into the interstitial space. HSA function can be also altered in disease with reduced albumin binding capacity and increased production of modified isoforms. HAS has been used as volume expander in critical illness, but received criticism due to cost and concerns regarding safety. More recent studies confirmed the safety of HAS, but failed to show any survival benefit compared to the cheaper crystalloid fluids, therefore limiting its use. On the contrary, in cirrhosis there is robust data to support the efficacy of HAS for the prevention of circulatory dysfunction post-large volume paracentesis and in the context of spontaneous bacterial peritonitis, and for the treatment of hepato-renal syndrome and hypervolaemic hyponatraemia. It is likely that not only the oncotic properties of HAS are beneficial in cirrhosis, but also its functional properties, as HAS replaces the dysfunctional HSA. The role of HAS as the resuscitation fluid of choice in critically ill patients with cirrhosis, beyond the established indications for HAS use, should be addressed in future studies. PMID:26981172

  8. Characterization of solute binding at human serum albumin site II and its geometry using a biochromatographic approach.

    PubMed Central

    Peyrin, E; Guillaume, Y C; Guinchard, C

    1999-01-01

    Chiral recognition mechanism relationships for binding at site II on human serum albumin (HSA) were investigated using D, L dansyl amino acids. Sodium phosphate salt was used as a solute-HSA interaction modifier. A new model was developed using a biochromatographic approach to describe the variation in the transfer equilibrium constant with the salt concentration, i.e., the nature of the interactions. The solute binding was divided into two salt concentration ranges c. For the low c values, below 0.03 M, the nonstereoselective interactions constituted the preponderant contribution to the variation in the solute binding with the salt concentration. For the high c values, above 0.03 M, the solute binding was governed by the hydrophobic effect and the stereoselective interactions. The different contributions implied in the binding process provided an estimation of both the surface charge density (sigma/F) and the surface area of the site II binding cavity accessible to solvent, which were found to be equal to around 10.10(-7) mol/m(2) and 2 nm(2). As well, the excess of sodium ions excluded by the solute transfer from the surface area of the pocket were about(-0.7) for dansyl norvaline and (-0.8) for dansyl tryptophan. PMID:10465735

  9. Characterization of the Solution Structure of Human Serum Albumin Loaded with a Metal Porphyrin and Fatty Acids

    PubMed Central

    Junk, Matthias J.N.; Spiess, Hans W.; Hinderberger, Dariush

    2011-01-01

    The structure of human serum albumin loaded with a metal porphyrin and fatty acids in solution is characterized by orientation-selective double electron-electron resonance (DEER) spectroscopy. Human serum albumin, spin-labeled fatty acids, and Cu(II) protoporphyrin IX—a hemin analog—form a fully self-assembled system that allows obtaining distances and mutual orientations between the paramagnetic guest molecules. We report a simplified analysis for the orientation-selective DEER data which can be applied when the orientation selection of one spin in the spin pair dominates the orientation selection of the other spin. The dipolar spectra reveal a dominant distance of 3.85 nm and a dominant orientation of the spin-spin vectors between Cu(II) protoporphyrin IX and 16-doxyl stearic acid, the electron paramagnetic resonance reporter group of the latter being located near the entry points to the fatty acid binding sites. This observation is in contrast to crystallographic data that suggest an asymmetric distribution of the entry points in the protein and hence the occurrence of various distances. In conjunction with the findings of a recent DEER study, the obtained data are indicative of a symmetric distribution of the binding site entries on the protein's surface. The overall anisotropic shape of the protein is reflected by one spin-spin vector orientation dominating the DEER data. PMID:21539799

  10. Structure and interparticle interactions of bovine serum albumin in solution studied by small-angle neutron scattering

    SciTech Connect

    Bendedouch, D.; Chen, S.H.

    1983-04-28

    A series of small-angle neutron scattering (SANS) measurements were carried out on dilute and moderately concentrated bovine serum albumin (BSA) solutions at two different pH values and at t = 35/sup 0/C. The amount of bound water to the protein was deduced from the zero-contrast point of dilute BSA solutions, in D/sub 2/O and H/sub 2/O solvent mixtures. Detailed analysis of the intensity spectrum from the most dilute BSA solution in D/sub 2/O yields a prolate ellipsoidal shape (a,b,b) of the protein molecule with a = 70 angstrom and b = 20 angstrom. At moderate concentrations, pH 7, with or without salt (LiCl) added, the intensity spectra can be fitted satisfactorily by taking into account both the ellipsoidal shape of the particle and an interparticle interference factor (S(Q)). Calculation of S(Q) assumes a model of equivalent charged hard spheres interacting through a repulsive potential. For moderately concentrated solutions at pH 5.1, S(Q) can be accounted for by introducing an attractive potential between the particles.

  11. Simultaneous photometric determination of albumin and total protein in animal blood plasma employing a multicommutated flow system to carried out on line dilution and reagents solutions handling

    NASA Astrophysics Data System (ADS)

    Luca, Gilmara C.; Reis, Boaventura F.

    2004-02-01

    An automatic flow procedure for the simultaneous determination of albumin and total protein in blood plasma samples is proposed. The flow network comprised a set of three-way solenoid valves assembled to implement the multicommutation. The flow set up was controlled by means of a computer equipped with an electronic interface card which running a software wrote in QUICKBASIC 4.5 performed on line programmed dilution to allow the determination of both albumin and total protein in blood plasma. The photometric methods based on Bromocresol Green and Biuret reagents were selected for determination of albumin and total protein, respectively. Two LEDs based photometers coupled together the flow cells were employed as detector. After the adjustment of the operational parameters the proposed system presented the following features: an analytical throughput of 45 sample processing per hour for two analytes; relative standard deviations of 1.5 and 0.8% ( n=10) for a typical sample presenting 34 g l -1 albumin and 90 g l -1 total protein, respectively; linear responses ranging from 0 to 15 g l -1 albumin ( r=0.998) and total protein ( r=0.999); sample and reagents consumption, 140 μl serum solution, 0.015 mg VBC and 0.432 mg CuSO 4 per determination, respectively. Applying the paired t-test between results obtained using the proposed system and reference methods no significant difference at 95 and 90% confidence level for albumin and total protein, respectively, were observed.

  12. The studies of density, apparent molar volume, and viscosity of bovine serum albumin, egg albumin, and lysozyme in aqueous and RbI, CsI, and DTAB aqueous solutions at 303.15 K.

    PubMed

    Singh, Man; Chand, Hema; Gupta, K C

    2005-06-01

    Density (rho), apparent molar volume (V(phi)), and viscosity (eta) of 0.0010 to 0.0018% (w/v) of bovine serum albumin (BSA), egg albumin, and lysozyme in 0.0002, 0.0004, and 0.0008 M aqueous RbI and CsI, and (dodecyl)(trimethyl)ammonium bromide (DTAB) solutions were obtained. The experimental data were regressed against composition, and constants are used to elucidate the conformational changes in protein molecules. With salt concentration, the density of proteins is found to decrease, and the order of the effect of additives on density is observed as CsI > RbI > DTAB. The trend of apparent molar volume of proteins is found as BSA > egg-albumin > lysozyme for three additives. In general, eta values of BSA remain higher for all compositions of RbI than that of egg-albumin for CsI and DTAB. These orders of the data indicate the strength of intermolecular forces between proteins and salts, and are helpful for understanding the denaturation of proteins.

  13. Direct measurement of interaction forces between bovine serum albumin and poly(ethylene oxide) in water and electrolyte solutions.

    PubMed

    Acuña, Sergio M; Bastías, José M; Toledo, Pedro G

    2017-01-01

    The net interaction between a probe tip coated with bovine serum albumin (BSA) protein and a flat substrate coated with poly(ethylene oxide) (PEO) polymer was measured directly on approach in water and electrolyte solutions using AFM. The approach force curve between the two surfaces was monotonically repulsive in water and in electrolyte solutions. At pH ~5, slightly above the isoelectric point (pI) of BSA, and at large distances, the force was dominated by electrostatic repulsion between the oxygen atoms of the incoming protein with those belonging to the ether groups of PEO. Such repulsive force and range decreased in NaCl. Under physiological conditions, pH 6, BSA is definitely charged and the electrostatic repulsion with ether groups in PEO appears at larger separation distances. Interestingly, at pH 4, below the pI of BSA, the repulsion decreased because of an attractive, although weak, electrostatic force that appeared between the ether groups in PEO and the positively charged amino groups of BSA. However, for all solution conditions, once compression of PEO begun, the net repulsion was always dominated by short-range polymeric steric repulsion and repulsive enthalpy penalties for breaking PEO-water bonds. Results suggest that PEO in mushroom conformation may also be effective in reducing biofouling.

  14. Direct measurement of interaction forces between bovine serum albumin and poly(ethylene oxide) in water and electrolyte solutions

    PubMed Central

    Bastías, José M.; Toledo, Pedro G.

    2017-01-01

    The net interaction between a probe tip coated with bovine serum albumin (BSA) protein and a flat substrate coated with poly(ethylene oxide) (PEO) polymer was measured directly on approach in water and electrolyte solutions using AFM. The approach force curve between the two surfaces was monotonically repulsive in water and in electrolyte solutions. At pH ~5, slightly above the isoelectric point (pI) of BSA, and at large distances, the force was dominated by electrostatic repulsion between the oxygen atoms of the incoming protein with those belonging to the ether groups of PEO. Such repulsive force and range decreased in NaCl. Under physiological conditions, pH 6, BSA is definitely charged and the electrostatic repulsion with ether groups in PEO appears at larger separation distances. Interestingly, at pH 4, below the pI of BSA, the repulsion decreased because of an attractive, although weak, electrostatic force that appeared between the ether groups in PEO and the positively charged amino groups of BSA. However, for all solution conditions, once compression of PEO begun, the net repulsion was always dominated by short-range polymeric steric repulsion and repulsive enthalpy penalties for breaking PEO-water bonds. Results suggest that PEO in mushroom conformation may also be effective in reducing biofouling. PMID:28296940

  15. Analysis of albumin hologram

    NASA Astrophysics Data System (ADS)

    Ordóñez-Padilla, M. J.; Olivares-Pérez, A.; Berriel-Valdos, L. R.; Ortiz-Gutiérrez, M.; Villa-Manríquez, J. F.

    2012-03-01

    We present the characterizations of the photosensitive film made with albumins gallus gallus and callipepla cali, with the purpose to make holographic recording. Albumin was combined with propylene glycol, to build colloidal systems by adding the ammonium dichromate solution as photosensitive salt at certain concentrations. Hence, we conducted the photo-oxidation process with laser, λ=442nm. Obtaining holograms that allowed the analysis of the diffraction efficiency parameter. One of the objectives of this work was to obtain some mechanical and chemical stability of films made with albumin when prepared with propylene glycol. At once, experimental studies were performed to compare the results of the holographic recording films between chicken albumin and quail albumin film to prove the recording capabilities and to quantify the diffraction efficiency in holographic grating made with each kind of albumin.

  16. Surface characterization of human serum albumin and sodium perfluorooctanoate mixed solutions by pendant drop tensiometry and circular dichroism.

    PubMed

    Messina, Paula; Prieto, Gerardo; Dodero, Verónica; Cabrerizo-Vílchez, M A; Maldonado-Valderrama, J; Ruso, Juan M; Sarmiento, Félix

    2006-06-15

    The interfacial behavior of mixed human serum albumin (HSA)/sodium perfluorooctanoate (C8FONa) solutions is examined by using two experimental techniques, pendant drop tensiometry and circular dichroism spectroscopy. Through the analysis of the surface tension of the mixed solutions, surface competitive adsorption at the air-water interface between C8FONa and HSA is detected. The dynamic adsorption curves exhibit the distinct regimes in their time-dependent surface tension. The nature of these regimes is further analyzed in terms of the variation of the molecules surface areas. As a consequence, a compact and dense structure was formed where protein molecules were interconnected and overlapped. Thus, a reduction of the area occupied per molecule from 100 to 0.2 nm(2) is interpreted as a gel-like structure at the surface. The presence of the surfactant seems to favor the formation of this interfacial structure. Finally, measurements of circular dichroism suggests a compaction of the protein due to the association with the surfactant given by an increase of alpha-helix structure in the complexes as compared to that of pure protein.

  17. Study of twenty preparations of human albumin solution which failed in quality control testing due to elevated sodium content, a poor internal quality control at manufacturing unit.

    PubMed

    Prasad, J P; Madhu, Y; Singh, Surinder; Soni, G R; Agnihotri, N; Singh, Varsha; Kumar, Pradeep; Jain, Nidhi; Prakash, Anu; Singh, Varun

    2016-11-01

    Current study is conducted in our laboratory due to failure in quality control testing of twenty batches of Human Albumin solution in which sodium content is higher than the prescribed limit. These batches are received in short duration from indigenous manufacturer and is the first incident of failure of Human albumin preparation in sodium content of manufacturer. On request of manufacturer, study is conducted to rule out the cause. Repeat testing of each out of specification batch is conducted and a trend analysis is drawn between our findings and manufacturer's results, also study of trend analysis of manufacturer for the last one year. Trend analysis data indicated towards poor consistency of batches with major shift at various time intervals in sodium content of human albumin preparation. Further analysis rule out that non-traceable quality of standard used in the internal quality control testing by manufacturer is the root cause of the problem.

  18. AGE-modified albumin containing infusion solutions boosts septicaemia and inflammation in experimental peritonitis

    PubMed Central

    Humpert, Per M.; Lukic, Ivan K.; Thorpe, Suzanne R.; Hofer, Stefan; Awad, Ezzat M.; Andrassy, Martin; Deemer, Elizabeth K.; Kasper, Michael; Schleicher, Erwin; Schwaninger, Markus; Weigand, Markus A.; Nawroth, Peter P.; Bierhaus, Angelika

    2009-01-01

    HSA preparations for i.v. use are administered in critically ill patients. Although increasing intravascular osmotic pressure seems to be a pathophysiologically orientated treatment, clinical trials do not indicate a benefit for mortality in HSA-treated patients. Instead, there is evidence for inflammatory reactions upon infusion of different HSA batches. A neglected issue concerning the safety and quality of these therapeutics is processing-related post-transcriptional protein modifications, such as AGEs. We therefore tested the hypothesis that commercially available infusion solutions contain AGEs and studied whether these protein modifications influence outcome and inflammation in a murine model of sepsis induced by CLP. Screening of different HSA and Ig preparations in this study revealed an up to approximate tenfold difference in the amount of AGE modifications. Application of clinically relevant concentrations of CML-modified HSA in CLP led to increased inflammation and enhanced mortality in wild-type mice but not in mice lacking the RAGE. Lethality was paralleled by increased activation of the proinflammatory transcription factor NF-κB, NF-κB-dependent gene expression, and infiltration of inflammatory cells in the peritoneal cavity. This study implies that infusion solutions containing a high load of the AGE-modified protein have the potential to activate RAGE/NF-κB-mediated inflammatory reactions, causing increased mortality in experimental peritonitis. PMID:19401390

  19. Albumin Test

    MedlinePlus

    ... may also be ordered to evaluate a person's nutritional status. ^ Back to top When is it ordered? An ... albumin test to check or monitor a person's nutritional status. However, since albumin concentrations respond to a variety ...

  20. Adsorption of bovine serum albumin on Zr co-sputtered a-C(:H) films: Implication on wear behaviour.

    PubMed

    Escudeiro, A; Polcar, T; Cavaleiro, A

    2014-11-01

    The use of protective coatings in biomedical field is an ongoing scientific challenge. Among different materials, carbon-based coatings are considered a potential surface treatment for orthopaedic implants. In this study, the effect of Zr incorporation in amorphous carbon coatings on the wear behaviour under protein containing lubrication was investigated. The coatings were deposited by dc unbalanced magnetron sputtering in Ar (non-hydrogenated) and Ar+CH4 (hydrogenated) discharges onto Ti based biomedical substrate. To improve the adhesion between the film and substrate a functional gradient Ti based layer was deposited (~550 nm). The surface wettability was evaluated to assess the effect of the Zr and hydrogen content. The films with Zr were found to be hydrophobic enhancing the protein adsorption onto the surface; no significant differences were found when H was incorporated in the films. The adsorption layer characterized by X-ray photoelectron spectroscopy showed a well defined nitrogen peak originating from the organic layer. The tribological properties of the film were evaluated by unidirectional pin-on-disc testing with diluted bovine serum lubrication and physiological solution at 37 ± 3C°. The friction and the wear of the coatings were very low compared to uncoated substrates in both lubrication conditions. The ability of the surfaces to adsorb proteins was considered as the driving force for wear resistance acting as a protecting layer. In addition, the incorporation of Zr decreased the wear of the counterbody (Ti alloy) due to higher albumin adsorption. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Heterogeneity in Desiccated Solutions: Implications for Biostabilization

    PubMed Central

    Ragoonanan, Vishard; Aksan, Alptekin

    2008-01-01

    Biopreservation processes such as freezing and drying inherently introduce heterogeneity. We focused on exploring the mechanisms responsible for heterogeneity in isothermal, diffusively dried biopreservation solutions that contain a model protein. The biopreservation solutions used contained trehalose (a sugar known for its stabilization effect) and salts (LiCl, NaCl, MgCl2, and CaCl2). Performing Fourier transform infrared spectroscopy analysis on the desiccated droplets, spatial distributions of the components within the dried droplet, as well as their specific interactions, were investigated. It was established that the formation of multiple thermodynamic states was induced by the spatial variations in the cosolute concentration gradients, directly affecting the final structure of the preserved protein. The spatial distribution gradients were formed by two competing flows that formed within the drying droplet: a dominant peripheral flow, induced by contact line pinning, and the Marangoni flow, induced by surface tension gradients. It was found that the changes in cosolute concentrations and drying conditions affected the spatial heterogeneity and stability of the product. It was also found that trehalose and salts had a synergistic stabilizing effect on the protein structure, which originated from destructuring of the vicinal water, which in turn mediated the interactions of trehalose with the protein. This interaction was observed by the change in the glycosidic CO, and the CH stretch vibrations of the trehalose molecule. PMID:18055531

  2. Aluminum toxicity and albumin.

    PubMed

    Kelly, A T; Short, B L; Rains, T C; May, J C; Progar, J J

    1989-01-01

    During a study of priming solutions for extracorporeal membrane oxygenation (ECMO) in the intensive care nursery, it was discovered that those solutions using certain brands of 25% albumin contained aluminum levels within the toxic range. When the brand was changed to a brand known to have a lower aluminum (Al) content, a marked drop in priming solution Al levels was measured. The heat exchanger was examined as a possible source of soluble Al. No evidence of elevated Al levels was found in fluids perfusing this heat exchanger when compared with a stainless steel heat exchanger. The Al content of various blood products was evaluated along with various brands of 5% albumin and 25% albumin.

  3. Microglial AGE-albumin is critical for neuronal death in Parkinson’s disease: a possible implication for theranostics

    PubMed Central

    Bayarsaikhan, Enkhjargal; Bayarsaikhan, Delger; Lee, Jaesuk; Son, Myeongjoo; Oh, Seyeon; Moon, Jeongsik; Park, Hye-Jeong; Roshini, Arivazhagan; Kim, Seung U; Song, Byoung-Joon; Jo, Seung-Mook; Byun, Kyunghee; Lee, Bonghee

    2015-01-01

    Advanced glycation end products (AGEs) are known to play an important role in the pathogenesis of neurodegenerative diseases, including Parkinson’s disease (PD), by inducing protein aggregation and cross-link, formation of Lewy body, and neuronal death. In this study, we observed that AGE-albumin, the most abundant AGE product in the human PD brain, is synthesized in activated microglial cells and accumulates in the extracellular space. AGE-albumin synthesis in human-activated microglial cells is distinctly inhibited by ascorbic acid and cytochalasin treatment. Accumulated AGE-albumin upregulates the receptor to AGE, leading to apoptosis of human primary dopamine (DA) neurons. In animal experiments, we observed reduced DA neuronal cell death by treatment with soluble receptor to AGE. Our study provides evidence that activated microglial cells are one of the main contributors in AGE-albumin accumulation, deleterious to DA neurons in human and animal PD brains. Finally, activated microglial AGE-albumin could be used as a diagnostic and therapeutic biomarker with high sensitivity for neurodegenerative disorders, including PD. PMID:27601894

  4. Holograms of fluorescent albumin

    NASA Astrophysics Data System (ADS)

    Ordóñez-Padilla, M. J.; Olivares-Pérez, A.; Berriel-Valdos, L. R.; Mejias-Brizuela, N. Y.; Fuentes-Tapia, I.

    2011-09-01

    We report the characterization and analysis of photochromic films gallus gallus albumin as a matrix modified for holographic recording. Photo-oxidation of homogeneous mixtures prepared with albumin-propylene glycol, to combine chemically with aqueous solution of ammonium dichromate at certain concentrations. We analyzed the diffraction gratings, through the diffraction efficiency of the proposed material. Also, eosin was used as a fluorescent agent, so it is found that produces an inhibitory effect, thus decreasing the diffraction efficiency of the matrices prepared in near-identical circumstances. The work was to achieve stability of albumin films, were prepared with propylene glycol. Finally, experimental studies were performed with films when subjected to aqueous solution of eosin (fluorescent agent) to verify the ability to increase or decrease in diffraction efficiency.

  5. Ultralow protein adsorbing coatings from clickable PEG nanogel solutions: benefits of attachment under salt-induced phase separation conditions and comparison with PEG/albumin nanogel coatings.

    PubMed

    Donahoe, Casey D; Cohen, Thomas L; Li, Wenlu; Nguyen, Peter K; Fortner, John D; Mitra, Robi D; Elbert, Donald L

    2013-03-26

    Clickable nanogel solutions were synthesized by using the copper catalyzed azide/alkyne cycloaddition (CuAAC) to partially polymerize solutions of azide and alkyne functionalized poly(ethylene glycol) (PEG) monomers. Coatings were fabricated using a second click reaction: a UV thiol-yne attachment of the nanogel solutions to mercaptosilanated glass. Because the CuAAC reaction was effectively halted by the addition of a copper-chelator, we were able to prevent bulk gelation and limit the coating thickness to a single monolayer of nanogels in the absence of the solution reaction. This enabled the inclusion of kosmotropic salts, which caused the PEG to phase-separate and nearly double the nanogel packing density, as confirmed by quartz crystal microbalance with dissipation (QCM-D). Protein adsorption was analyzed by single molecule counting with total internal reflection fluorescence (TIRF) microscopy and cell adhesion assays. Coatings formed from the phase-separated clickable nanogel solutions attached with salt adsorbed significantly less fibrinogen than other 100% PEG coatings tested, as well as poly(L-lysine)-g-PEG (PLL-g-PEG) coatings. However, PEG/albumin nanogel coatings still outperformed the best 100% PEG clickable nanogel coatings. Additional surface cross-linking of the clickable nanogel coating in the presence of copper further reduced levels of fibrinogen adsorption closer to those of PEG/albumin nanogel coatings. However, this step negatively impacted long-term resistance to cell adhesion and dramatically altered the morphology of the coating by atomic force microscopy (AFM). The main benefit of the click strategy is that the partially polymerized solutions are stable almost indefinitely, allowing attachment in the phase-separated state without danger of bulk gelation, and thus producing the best performing 100% PEG coating that we have studied to date.

  6. Ultralow protein adsorbing coatings from clickable PEG nanogel solutions: Benefits of attachment under salt-induced phase separation conditions and comparison with PEG/albumin nanogel coatings

    PubMed Central

    Donahoe, Casey D.; Cohen, Thomas L.; Li, Wenlu; Nguyen, Peter K.; Fortner, John D.; Mitra, Robi D.; Elbert, Donald L.

    2013-01-01

    Clickable nanogel solutions were synthesized by using the copper catalyzed azide/alkyne cycloaddition (CuAAC) to partially polymerize solutions of azide and alkyne functionalized poly(ethylene glycol) (PEG) monomers. Coatings were fabricated using a second click reaction: a UV thiol-yne attachment of the nanogel solutions to mercaptosilanated glass. Because the CuAAC reaction was effectively halted by the addition of a copper-chelator, we were able to prevent bulk gelation and limit the coating thickness to a single monolayer of nanogels in the absence of the solution reaction. This enabled the inclusion of kosmotropic salts, which caused the PEG to phase-separate and nearly double the nanogel packing density, as confirmed by Quartz Crystal Microbalance with Dissipation (QCM-D). Protein adsorption was analyzed by single molecule counting with total internal reflection fluorescence (TIRF) microscopy and cell adhesion assays. Coatings formed from the phase-separated clickable nanogel solutions attached with salt adsorbed significantly less fibrinogen than other 100% PEG coatings tested, as well as poly-L-lysine-g-PEG (PLL-g-PEG) coatings. However, PEG/albumin nanogel coatings still outperformed the best 100% PEG clickable nanogel coatings. Additional surface crosslinking of the clickable nanogel coating in the presence of copper further reduced levels of fibrinogen adsorption closer to those of PEG/albumin nanogel coatings. However, this step negatively impacted long-term resistance to cell adhesion and dramatically altered the morphology of the coating by atomic force microscopy (AFM). The main benefit of the click strategy is that the partially polymerized solutions are stable almost indefinitely, allowing attachment in the phase-separated state without danger of bulk gelation, and thus, producing the best performing 100% PEG coating that we have studied to date. PMID:23441808

  7. Reversible Aggregation of Albumin

    NASA Astrophysics Data System (ADS)

    Colby, Ralph H.; Oates, Katherine M. N.; Krause, Wendy E.; Jones, Ronald L.

    2004-03-01

    We explore the interactions in synovial fluid involving the polyelectrolyte sodium hyaluronate (NaHA) and plasma proteins in their native state (albumin and globulins). Rheological measurements on synovial fluid show it to be highly viscoelastic and also rheopectic (stress increases with time in steady shear). Equilibrium dialysis confirms the findings of Ogston and Dubin that there is no association between NaHA and albumin at physiological pH and salt. What we find instead is a reversible aggregation of albumin, with an association energy of order 3kT and commensurate association lifetime of order microseconds. Certain anti-inflammatory drugs are shown to prevent this reversible aggregation. The implications of these findings for synovial fluid and blood rheology are discussed.

  8. Synthesis of bovine serum albumin-protected high fluorescence Pt16-nanoclusters and their application to detect sulfide ions in solutions

    NASA Astrophysics Data System (ADS)

    Xu, Na; Li, Hong-Wei; Yue, Yuan; Wu, Yuqing

    2016-10-01

    Highly fluorescent (quantum yield, QY = 17%) Pt16-nanoclusters (Pt16-NCs@BSA) have been prepared via a one-step ultrasonic-assistance method by using cheap and easily available ascorbic acid as reductant and bovine serum albumin (BSA) as a stabilizing agent in aqueous solution. The fluorescence properties of the Pt-NCs@BSA can be easily controlled by optimizing conditions, and the products are extremely stable and could be used for the detection of sulfide ions (S2-) in solutions as a specific luminescence sensor. The present synthesis method is performed in one step, being cost-effective with a particularly short reaction time, which could be extended to the synthesis of other kinds of protein-protected Pt-NCs.

  9. Albumin versus crystalloid solutions in patients with the acute respiratory distress syndrome: a systematic review and meta-analysis.

    PubMed

    Uhlig, Christopher; Silva, Pedro L; Deckert, Stefanie; Schmitt, Jochen; de Abreu, Marcelo Gama

    2014-01-09

    In patients with acute respiratory distress syndrome (ARDS) fluid therapy might be necessary. The aim of this systematic review and meta-analysis is to determine the effects of colloid therapy compared to crystalloids on mortality and oxygenation in adults with ARDS. Randomized controlled trials (RCTs) were identified through a systematic literature search of MEDLINE, EMBASE, CENTRAL and LILACS. Articles published up to 15th February 2013 were independently screened, abstracted, and assessed (Cochrane Risk of Bias Tool) to provide evidence-based therapy recommendations. RCTs were eligible if they compared colloid versus crystalloid therapy on lung function, inflammation, damage or mortality in adults with ARDS. Primary outcome parameters were respiratory mechanics, gas exchange lung inflammation and damage as well as hospital mortality. Kidney function, need for renal replacement therapy, hemodynamic stabilization and intensive care unit (ICU) length of stay served as secondary outcomes. A total of 3 RCTs out of 4130 potential trials found in the databases were selected for qualitative and quantitative analysis totaling 206 patients who received either albumin or saline. Overall risk of bias was unclear to high in the identified trials. Calculated pooled risk of death was not statistically significant (albumin 34 of 100 (34.0%) versus 40 of 104 (38.5%), relative risk (RR) = 0.89, 95% confidence interval (CI) 0.62 to 1.28, P = 0.539). Weighted mean difference (WMD) in PaO2/FiO2 (mmHg) improved in the first 48 hours (WMD = 62, 95% CI 47 to 77, P <0.001, I2 = 0%) after therapy start and remained stable after 7 days (WMD = 20, 95% CI 4 to 36, P = 0.017, I2 = 0%). There is a high need for RCTs investigating the effects of colloids in ARDS patients. Based on the findings of this review, colloid therapy with albumin improved oxygenation but did not affect mortality.

  10. Albumin versus crystalloid solutions in patients with the acute respiratory distress syndrome: a systematic review and meta-analysis

    PubMed Central

    2014-01-01

    Introduction In patients with acute respiratory distress syndrome (ARDS) fluid therapy might be necessary. The aim of this systematic review and meta-analysis is to determine the effects of colloid therapy compared to crystalloids on mortality and oxygenation in adults with ARDS. Methods Randomized controlled trials (RCTs) were identified through a systematic literature search of MEDLINE, EMBASE, CENTRAL and LILACS. Articles published up to 15th February 2013 were independently screened, abstracted, and assessed (Cochrane Risk of Bias Tool) to provide evidence-based therapy recommendations. RCTs were eligible if they compared colloid versus crystalloid therapy on lung function, inflammation, damage or mortality in adults with ARDS. Primary outcome parameters were respiratory mechanics, gas exchange lung inflammation and damage as well as hospital mortality. Kidney function, need for renal replacement therapy, hemodynamic stabilization and intensive care unit (ICU) length of stay served as secondary outcomes. Results A total of 3 RCTs out of 4130 potential trials found in the databases were selected for qualitative and quantitative analysis totaling 206 patients who received either albumin or saline. Overall risk of bias was unclear to high in the identified trials. Calculated pooled risk of death was not statistically significant (albumin 34 of 100 (34.0%) versus 40 of 104 (38.5%), relative risk (RR) = 0.89, 95% confidence interval (CI) 0.62 to 1.28, P = 0.539). Weighted mean difference (WMD) in PaO2/FiO2 (mmHg) improved in the first 48 hours (WMD = 62, 95% CI 47 to 77, P <0.001, I2 = 0%) after therapy start and remained stable after 7 days (WMD = 20, 95% CI 4 to 36, P = 0.017, I2 = 0%). Conclusions There is a high need for RCTs investigating the effects of colloids in ARDS patients. Based on the findings of this review, colloid therapy with albumin improved oxygenation but did not affect mortality. PMID:24405693

  11. Theoretical and experimental studies on freezing point depression and vapor pressure deficit as methods to measure osmotic pressure of aqueous polyethylene glycol and bovine serum albumin solutions.

    PubMed

    Kiyosawa, Keitaro

    2003-05-01

    For survival in adverse environments where there is drought, high salt concentration or low temperature, some plants seem to be able to synthesize biochemical compounds, including proteins, in response to changes in water activity or osmotic pressure. Measurement of the water activity or osmotic pressure of simple aqueous solutions has been based on freezing point depression or vapor pressure deficit. Measurement of the osmotic pressure of plants under water stress has been mainly based on vapor pressure deficit. However, differences have been noted for osmotic pressure values of aqueous polyethylene glycol (PEG) solutions measured by freezing point depression and vapor pressure deficit. For this paper, the physicochemical basis of freezing point depression and vapor pressure deficit were first examined theoretically and then, the osmotic pressure of aqueous ethylene glycol and of PEG solutions were measured by both freezing point depression and vapor pressure deficit in comparison with other aqueous solutions such as NaCl, KCl, CaCl(2), glucose, sucrose, raffinose, and bovine serum albumin (BSA) solutions. The results showed that: (1) freezing point depression and vapor pressure deficit share theoretically the same physicochemical basis; (2) theoretically, they are proportional to the molal concentration of the aqueous solutions to be measured; (3) in practice, the osmotic pressure levels of aqueous NaCl, KCl, CaCl(2), glucose, sucrose, and raffinose solutions increase in proportion to their molal concentrations and there is little inconsistency between those measured by freezing point depression and vapor pressure deficit; (4) the osmotic pressure levels of aqueous ethylene glycol and PEG solutions measured by freezing point depression differed from the values measured by vapor pressure deficit; (5) the osmotic pressure of aqueous BSA solution measured by freezing point depression differed slightly from that measured by vapor pressure deficit.

  12. Heparin and albumin as part of the priming solution limits exposure to anticoagulation during hemodialysis: in vitro studies.

    PubMed

    Kyrk, Tobias; Bechara, Alex; Skagerlind, Malin; Stegmayr, Bernd

    2014-10-01

    Hemodialysis patients who are subject to increased risk of hemorrhage may need specific dialysis regimes to avoid bleeding. The aim of this study was to determine in vitro which of various anticoagulation options were most beneficial. 60 in vitro hemodialyses (HD) were performed in parallel using blood from healthy donors. The dialysis circuits were rinsed with either 1 L of 0.9% NaCl alone (n = 6), or with 1 L saline and the addition of either 5 mL 20% albumin (Alb, n = 6), 5,000 U of heparin (Hep, n = 6), Hep and Alb in combination (HA, n = 30), 20,000 U of Hep and Alb (4H-A, n = 6), and finally Hep and 20 mL 20% albumin (H-4A, n = 6). The blood was recirculated for a maximum of 192 min. Clotting was graded. A 192 min dialysis was completed with all series of HA, 4H-A, and H-4A, all with a slight grade of clotting. In contrast to the above settings (p = 0.002, Fisher's test), a total clotting of the dialysis circuit occurred for all series using the NaCl rinsing alone (median time to stop: 21, range:18-27 min, p = 0.026 compared to the HA setting) and for the Alb rinsing (median 26, range: 19-35 min, p = 0.028). Priming using HA, Hep, 4H-A, and H-4A reduced clotting and allowed 192 min of HD. Clinical studies need to confirm these data in vivo.

  13. Ion release and surface oxide composition of AISI 316L, Co-28Cr-6Mo, and Ti-6Al-4V alloys immersed in human serum albumin solutions.

    PubMed

    Karimi, Shima; Alfantazi, Akram M

    2014-07-01

    The long-term weight loss, ion release, and surface composition of 316L, Co-28Cr-6Mo and Ti-6Al-4V alloys were investigated in a simulated body environment. The samples were immersed in phosphate-buffered saline (PBS) solutions with various human serum albumin (HSA) concentrations for 8, 14, and 22 weeks. The specimens initially lost weight up to 14 weeks and then slightly gained weight. The analysis of the released ions was performed by induced coupled plasma-optical emission spectrometer (ICP-OES). The results revealed that the precipitation of the dissolved Fe and Co could cause the weight gain of the 316L and Co-28Cr-6Mo alloys. The surface chemistry of the specimens was determined by X-ray photoelectron spectroscopy (XPS). The XPS analysis of Co-28Cr-6Mo alloy showed that the interaction of Mo with HSA is different from Mo with bovine serum albumin (BSA). This was also observed for Na adsorption into the oxide layer of Ti-6Al-4V alloy in the presence of HSA and BSA.

  14. Implications of levels of serum mineral metabolism markers, albumin and C-reactive protein for treatment costs of patients on maintenance dialysis.

    PubMed

    Salonen, Tapani; Piirto, Juho; Reina, Tuomo; Saha, Heikki; Pasternack, Amos

    2007-01-01

    Secondary hyperparathyroidism, malnutrition and inflammation have been reported to associate with adverse outcomes in dialysis patients. However, little is known about the implications of these conditions for treatment costs. The cost data of all adult patients who had entered dialysis therapy at Tampere University Hospital between 1991 and 1996 and had remained on dialysis for at least 1 year were collected. results of measurements of parathyroid hormone (PTH), calcium, phosphorus, albumin and C-reactive protein (CRP) were obtained from the database of the hospital. Patients (n = 109), aged 57.0 +/- 14.9 years, included 57% men and 37% diabetics; 62% started on hemodialysis and 38% on peritoneal dialysis. Average daily costs were USD 161 (range 95-360). After controlling for patients' age, body mass index, gender, dialysis modality and primary renal disease, there was a positive correlation between average CRP and average costs and a negative correlation between albumin and costs. Correlations between mineral metabolism markers and costs were not found, but there was a trend towards lower cost among patients who achieved the Kidney Disease Outcomes Quality Initiative targets of calcium, phosphorus and PTH (USD 145 +/- 31) compared with those with nonoptimal levels (USD 165 +/- 48; p = 0.095). Costs of patients with at least one in-target PTH measurement were lower than costs of patients with constantly low PTH (USD 148 +/- 31 vs. 170 +/- 48; p = 0.01). Serum levels of albumin and CRP correlated with dialysis patients' treatment costs. Achieving the Kidney Disease Outcomes Quality Initiative targets may be associated with lower costs. Copyright 2007 S. Karger AG, Basel.

  15. A study of the molecular sources of nonideal osmotic pressure of bovine serum albumin solutions as a function of pH.

    PubMed

    Kanal, K M; Fullerton, G D; Cameron, I L

    1994-01-01

    The nonideal osmotic pressure of bovine serum albumin (BSA) solutions was studied extensively by Scatchard and colleagues. The extent of pH- and salt-dependent nonideality changes are large and unexplained. In 1992, Fullerton et al. derived new empirical expressions to describe solution nonideal colligative properties including osmotic pressure (Fullerton et al. 1992. Biochem. Cell Biol. 70:1325-1331). These expressions are based on the concepts of volume occupancy and hydration force. Nonideality is accurately described by a solute/solvent interaction parameter I and an "effective" osmotic molecular weight Ae. This paper uses the interaction-corrected nonideal expressions for osmotic pressure to calculate the hydration I values and "effective" osmotic molecular weight of BSA, Ae, as a function of pH. Both factors vary in a predictable manner due to denaturing of the BSA molecule. Both contribute to an increase in osmotic pressure for the same protein concentration as the solution pH moves away from the isoelectric point. Increased nonideality is caused by larger hydration resulting from larger solvent-accessible surface areas and by the decrease in "effective" osmotic molecular weight, Ae, due to segmental motion of denatured (filamentous) molecules.

  16. A study of the molecular sources of nonideal osmotic pressure of bovine serum albumin solutions as a function of pH.

    PubMed Central

    Kanal, K M; Fullerton, G D; Cameron, I L

    1994-01-01

    The nonideal osmotic pressure of bovine serum albumin (BSA) solutions was studied extensively by Scatchard and colleagues. The extent of pH- and salt-dependent nonideality changes are large and unexplained. In 1992, Fullerton et al. derived new empirical expressions to describe solution nonideal colligative properties including osmotic pressure (Fullerton et al. 1992. Biochem. Cell Biol. 70:1325-1331). These expressions are based on the concepts of volume occupancy and hydration force. Nonideality is accurately described by a solute/solvent interaction parameter I and an "effective" osmotic molecular weight Ae. This paper uses the interaction-corrected nonideal expressions for osmotic pressure to calculate the hydration I values and "effective" osmotic molecular weight of BSA, Ae, as a function of pH. Both factors vary in a predictable manner due to denaturing of the BSA molecule. Both contribute to an increase in osmotic pressure for the same protein concentration as the solution pH moves away from the isoelectric point. Increased nonideality is caused by larger hydration resulting from larger solvent-accessible surface areas and by the decrease in "effective" osmotic molecular weight, Ae, due to segmental motion of denatured (filamentous) molecules. PMID:8130335

  17. Ag(I)-bovine serum albumin hydrosol-mediated formation of Ag3PO4/reduced graphene oxide composites for visible-light degradation of Rhodamine B solution.

    PubMed

    Ma, Peiyan; Chen, Anliang; Wu, Yan; Fu, Zhengyi; Kong, Wei; Che, Liyuan; Ma, Ruifang

    2014-03-01

    A cost-effective Ag(I)-bovine serum albumin (BSA) supramolecular hydrosol strategy was utilized to assemble Ag3PO4 nanospheres onto reduced graphene oxide (rGO) sheets. The obtained composites were characterized by X-ray diffraction, scanning electron microscopy, transmission electron microscopy, atomic force microscopy, X-ray photoelectron spectroscopy, UV-vis absorption spectroscopy and Fourier transform infrared spectroscopy. Compared with the pure Ag3PO4 crystals and Ag3PO4 particles prepared with Ag(I)-BSA hydrosol as precursor, the Ag3PO4/rGO composites obtained with different content of graphene oxide indicated improved visible-light-driven photocatalysis activity for the decomposition of Rhodamine B aqueous solution. The results pointed to the possibility of synthesizing graphene-based photocatalysts by metal ion-BSA hydrosol. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. Spectroscopic insight into the interaction of bovine serum albumin with imidazolium-based ionic liquids in aqueous solution.

    PubMed

    Satish, Lakkoji; Millan, Sabera; Sahoo, Harekrushna

    2016-11-03

    The study of protein-ionic liquid interactions is very important because of the widespread use of ionic liquids as protein stabilizer in the recent years. In this work, the interaction of bovine serum albumin (BSA) with different imidazolium-based ionic liquids (ILs) such as [1-ethyl-3-methyl-imidazolium ethyl sulfate (EmimESO4 ), 1-ethyl-3-methyl-imidazolium chloride (EmimCl) and 1-butyl-3-methyl-imidazolium chloride (BmimCl)] has been investigated using different spectroscopic techniques. The intrinsic fluorescence of BSA is quenched by ILs by the dynamic mechanism. The thermodynamic analysis demonstrates that very weak interactions exist between BSA and ILs. 8-Anilino-1-naphthalenesulfonic acid (ANS) fluorescence and lifetime measurements reveal the formation of the compact structure of BSA in IL medium. The conformational changes of BSA were monitored by CD analysis. Temperature-dependent ultraviolet (UV) measurements were done to study the thermal stability of BSA. The thermal stability of BSA in the presence of ILs follows the trend EmimESO4  > EmimCl > BmimCl and in the presence of more hydrophobic IL, destabilization increases rapidly as a function of concentration.

  19. Solution structure and stability against digestion of rproBnIb, a recombinant 2S albumin from rapeseed: relationship to its allergenic properties.

    PubMed

    Pantoja-Uceda, David; Palomares, Oscar; Bruix, Marta; Villalba, Mayte; Rodríguez, Rosalía; Rico, Manuel; Santoro, Jorge

    2004-12-28

    NMR spectroscopy has been used to determine the solution structure of the precursor form of the recombinant napin BnIb, rproBnIb, a 2S albumin, 109-residue protein from the seeds of Brassica napus. More than 90% of the side-chain proton resonances were unambiguously assigned from the analysis of two-dimensional correlation (COSY), total correlation (TOCSY), and nuclear Overhauser effect (NOESY) spectra. The final structures were computed by using restrained molecular dynamics on the basis of 1316 upper-limit distance constraints derived from NOE cross-correlation intensities. The computed structures exhibited a root-mean-square deviation (RMSD) radius of 0.66 A for the backbone and 1.16 A for the side-chain heavy atoms of the structural core. The resulting structure consists of five amphipathic helices arranged in a right-handed super helix, a folding motif found in other proteins of the prolamin superfamily. As in the case of the mature protein, the recombinant precursor behaves as a plant food allergen. To trace out the origin and characteristics of its allergenic properties, rproBnIb was assayed against simulated gastric fluid and found to be very resistant to proteolysis. Also, heat treatment of the protein followed up to 85 degrees C by circular dichroism showed a very limited unfolding, which was recovered after cooling to 20 degrees C, indicating a high thermal stability. These results suggest that rproBnIb, as other 2S albumins, may be able to reach the gut immune system intact. A comparison of the putative epitopes against IgE antibodies of the three members of the prolamine family [2S albumins, nonspecific lipid transfer proteins (nsLTPs), and alpha-amylase/trypsin inhibitors] indicates that there are not common surfaces of interaction with IgE. Though the epitopes appear to be located in different regions of the proteins, they do comply with the requirements of being solvent-exposed and flexible.

  20. Debate: Albumin administration should not be avoided

    PubMed Central

    Allison, Simon P; Lobo, Dileep N

    2000-01-01

    The recent Cochrane report on albumin administration is analysed and criticised on the grounds of clinical methodology, content and interpretation. Although it is naïve and illogical to treat hypoalbuminaemia with albumin infusions, a more balanced view on the use of albumin for resuscitation in acute hypovolaemia is necessary. Once the acute phase of critical illness is past, interstitial volume is often expanded causing oedema, with a low plasma volume. We argue for the use of salt-poor albumin solutions in this situation and conclude that, on current evidence, the assertion that albumin should be avoided in all situations is irrational and untenable. PMID:11211855

  1. Implications of bioactive solute transfer from hosts to parasitic plants.

    PubMed

    Smith, Jason D; Mescher, Mark C; De Moraes, Consuelo M

    2013-08-01

    Parasitic plants--which make their living by extracting nutrients and other resources from other plants--are important components of many natural ecosystems; and some parasitic species are also devastating agricultural pests. To date, most research on plant parasitism has focused on nutrient transfer from host to parasite and the impacts of parasites on host plants. Far less work has addressed potential effects of the translocation of bioactive non-nutrient solutes-such as phytohormones, secondary metabolites, RNAs, and proteins-on the development and physiology of parasitic plants and on their subsequent interactions with other organisms such as insect herbivores. A growing number of recent studies document the transfer of such molecules from hosts to parasites and suggest that they may have significant impacts on parasite physiology and ecology. We review this literature and discuss potential implications for management and priorities for future research.

  2. Influence of surface wettability on the tribological properties of laser textured Co-Cr-Mo alloy in aqueous bovine serum albumin solution

    NASA Astrophysics Data System (ADS)

    Qin, Liguo; Lin, Ping; Zhang, Yali; Dong, Guangneng; Zeng, Qunfeng

    2013-03-01

    Surface wettability behaviors of three kinds of laser textured Co-Cr-Mo alloy surfaces (arrays of circular, triangular and square shape dimples) were evaluated in aqueous bovine serum albumin (BSA) solution. The tribological properties of laser textured Co-Cr-Mo alloy were investigated by pin-on-disc reciprocating tribometer under BSA lubrication. The wetting surfaces ranging from superhydrophilic (CA = 21.5°) to superhydrophobic (CA = 142.2°) were obtained by dual/combined surface modification including laser surface texturing (LST) and further fluoro-alkyl silane (FAS). It was found that surface wettability behaviors of Co-Cr-Mo alloy surfaces were closely related to their tribological behaviors in BSA solution. Results showed that the contact angle of circular dimple was the most stable, sliding time of the friction pair reaching steady state stage was shortest and coefficient of friction was minimum among three regular layout shapes of dimples during the tribological tests. It suggests that the combined surface modification of LST and FAS is a promising method to improve the tribological performances and prolong the service life of Co-Cr-Mo orthopedic implants.

  3. Technical Solutions to Ensure Safe Yttrium-90 Radioembolization in Patients With Initial Extrahepatic Deposition of {sup 99m}Technetium-Albumin Macroaggregates

    SciTech Connect

    Barentsz, M. W.; Vente, M. A. D.; Lam, M. G. E. H.; Smits, M. L. J.; Nijsen, J. F. W.; Seinstra, B. A.; Rosenbaum, C. E. N. M.; Verkooijen, H. M.; Zonnenberg, B. A.; Van den Bosch, M. A. A. J.

    2011-10-15

    Purpose: To evaluate the incidence of extrahepatic deposition of technetium-99m-labeled albumin macroaggregates ({sup 99m}Tc-MAA) after pretreatment angiography, before yttrium-90 radioembolizaton ({sup 90}Y-RE), and to report on technical solutions that can be used to ensure safe delivery of {sup 90}Y-microspheres in patients with initial extrahepatic deposition. Materials and Methods: A retrospective analysis of 26 patients with primary and secondary liver malignancies, who were scheduled for treatment with {sup 90}Y-RE in our institution in 2009, was performed. The angiograms and single-photon emission computed tomography images of all patients were reviewed by an interventional radiologist and a nuclear medicine physician, respectively, to identify and localize extrahepatic deposition of {sup 99m}Tc-MAA when present. Subsequently, the technical solutions were used to successfully perform {sup 90}Y-RE in these patients were evaluated and described. Results: Extrahepatic deposition of {sup 99m}Tc-MAA was observed in 8 of 26 patients (31%). In 7 of 8 patients, a second pretreatment angiography was performed to detect the cause of extrahepatic deposition. The technical solutions to enable safe {sup 90}Y microspheres delivery included more distal placement of the microcatheter in the proper/right hepatic artery in 4 of 7 (57%) patients; (super)selective catheterization of multiple segmental branches in 2 of 7 (29%); and additional coiling of a newly detected branch in the remaining patient (14%). This was confirmed by a second MAA procedure. {sup 90}Y-RE was eventually performed in 25 of 26 (96%) patients. No procedure-related complications (<30 days) were observed. Conclusion: Extrahepatic deposition of {sup 99m}Tc-MAA after pretreatment angiography did occur in 8 of 26 (31%) patients. The technical solutions as presented allowed safe {sup 90}Y-RE delivery in 25 of 26 (96%) patients.

  4. Clinical Implications Associated With the Posttranslational Modification-Induced Functional Impairment of Albumin in Oxidative Stress-Related Diseases.

    PubMed

    Watanabe, Hiroshi; Imafuku, Tadashi; Otagiri, Masaki; Maruyama, Toru

    2017-09-01

    Recent research findings indicate that the posttranslational modification of human serum albumin (HSA) such as oxidation, glycation, truncation, dimerization, and carbamylation is related to certain types of diseases. We report herein on a simple and rapid analytical method, using an electrospray ionization time-of-flight mass spectrometry technique, that allows posttranslational modifications of HSA to be quantitatively and qualitatively evaluated with a high degree of sensitivity. In patients with chronic liver disease, chronic renal disease, and diabetes mellitus, an increase in the level of oxidized cysteine-34 (Cys-34) of HSA accompanied by a decrease in the level of reduced Cys-34 was observed. The redox status of Cys-34 was correlated with ligand binding and the antioxidative functions of HSA. Available evidence indicates that monitoring the redox state of Cys-34 not only could be a useful marker for evaluating the progression of disease and its complications but also would permit therapeutic efficacy to be predicted. The redox state of Cys-34 was also used as an index of the quality of HSA preparations. These data suggest that monitoring the posttranslational modifications of HSA can be important, because the function of HSA is related not only to its serum concentration but also to the preservation of its structural integrity under disease conditions. Copyright © 2017. Published by Elsevier Inc.

  5. The albumin-bilirubin grade improves hepatic reserve estimation post-sorafenib failure: implications for drug development.

    PubMed

    Pinato, D J; Yen, C; Bettinger, D; Ramaswami, R; Arizumi, T; Ward, C; Pirisi, M; Burlone, M E; Thimme, R; Kudo, M; Sharma, R

    2017-03-01

    Drug development in hepatocellular carcinoma (HCC) is limited by disease heterogeneity, with hepatic reserve being a major source of variation in survival outcomes. The albumin-bilirubin (ALBI) grade is a validated index of liver function in patients with HCC. To test the accuracy of the ALBI grade in predicting post-sorafenib overall survival (PSOS) in patients who permanently discontinued treatment. From a prospectively maintained international database of 447 consecutive referrals, we derived 386 eligible patients treated with sorafenib within Barcelona Clinic Liver Cancer C stage (62%), 75% of whom were of Child class A at initiation. Clinical variables at sorafenib discontinuation were analysed for their impact on post-sorafenib overall survival using uni- and multivariable analyses. Median post-sorafenib overall survival of the 386 eligible patients was 3.4 months and median sorafenib duration was 2.9 months, with commonest causes of cessation being disease progression (68%) and toxicity (24%). At discontinuation, 92 patients (24%) progressed to terminal stage, due to worsening Child class to C in 40 (10%). Median post-sorafenib overall survival in patients eligible for second-line therapies (n = 294) was 17.5, 7.5 and 1.9 months according respectively to ALBI grade 1, 2 and 3 (P < 0.001). The ALBI grade at sorafenib discontinuation identifies a subset of patients with prolonged stability of hepatic reserve and superior survival. This may allow improved patient selection for second-line therapies in advanced HCC. © 2017 John Wiley & Sons Ltd.

  6. Evolutions and equilibrium parameters of foam films from individual solutions of Bovine serum albumin, n-dodecyl-β-D-maltoside and from their mixed solutions

    NASA Astrophysics Data System (ADS)

    Gerasimova, Anelia Tsvetanova; Angarska, Jana Krumova; Tachev, Krasimir Dimov

    2017-03-01

    The evolutions of thinning of films from individual solutions of BSA, C12G2 and from their mixed solutions with molar ratios 1:1, 1:7.5, 1:50 and 1:100 with pH = 4.9 were recorded by modified (with video camera) interferometric method. Based on them the stages through which the film goes from its formation to the equilibrium state were distinguished. It was shown that: (i) the difference between the kinetic of drainage of films stabilized by high and low molecular surfactants is drastic; (ii) only the change of the pH solution under or above isoelectric point strongly retards the film drainage; (iii) the transition of the kinetic of thinning of films from mixed solutions from a kinetic typical for high molecular substances towards a kinetic for low substances depends on the molar ratio between the components in the solution. From the picture of film corresponding to its equilibrium state the type of film was determined. From the analysis of this picture the equilibrium thickness and contact angle were calculated. It was found that the criterion for Newtonium black films (based on the values of film thickness and contact angle) is not directly applicable for films from protein solutions or mixed solutions with the participation of proteins.

  7. [New recommendations on the use of human albumin solutions in patients with severe sepsis and septic shock. A critical evaluation of the literature].

    PubMed

    Latour-Pérez, J

    2013-01-01

    The third edition of the Surviving Sepsis Campaign guidelines opens the door to the use of albumin for fluid resuscitation in patients with severe sepsis and septic shock. This recommendation is based on a recent meta-analysis that included studies with evidence of insufficient plasma expansion in the control group and studies performed in children with malaria with clear statistical heterogeneity (P for interaction=.02). After excluding pediatric studies, the confidence interval of the effect estimate was consistent with a mortality excess in the group treated with albumin (OR=.87 [95%CI: .71 to 1.07]). Two new randomized studies reported after publication of the meta-analysis found no benefit in patients treated with albumin. Given the uncertainty about the true effect of albumin (due to the existence of indirectness and imprecision) and its cost considerations, it is suggested not to use albumin in the initial resuscitation of patients with severe sepsis and septic shock (GRADE2C).

  8. Urine Albumin and Albumin/ Creatinine Ratio

    MedlinePlus

    ... is detected in a urine sample collected at random , over 4 hours, or overnight, the test may ... both albumin and creatinine are measured in a random urine sample and an albumin/creatinine ratio (ACR) ...

  9. Immobilization of bovine serum albumin as a sensitive biosensor for the detection of trace lead ion in solution by piezoelectric quartz crystal impedance.

    PubMed

    Yin, Jian; Wei, Wanzhi; Liu, Xiaoying; Kong, Bo; Wu, Ling; Gong, Shuguo

    2007-01-01

    A biosensor based on bovine serum albumin (BSA) for the detection of lead (Pb(2+)) ion was developed and characterized. BSA was immobilized onto a colloidal Au-modified piezoelectric quartz crystal (PQC) as a biosensor for the detection of Pb(2+) ion by piezoelectric quartz crystal impedance (PQCI). Calibration curves for the quantification of Pb(2+) ion showed excellent linearity throughout the concentration range from 1.0 x 10(-7) to 3.0 x 10(-9)mol/L. The interaction between the Pb(2+) ions and the sensor chip is influenced significantly by the pH of the reaction buffer, and the optimal pH for the experiment was 5.4. Under the optimal conditions, the detection limit of 1.0 x 10(-9)mol/L for Pb(2+) was obtained. Kinetic parameters of the Pb(2+)-BSA interactions were also determined by using this chip. The sensor chip could be regenerated for use by dipping in the ethylenediaminetetraacetic acid (EDTA) solution for approximately 2h, and the chip was used to detect Pb(2+) ion for eight times without obvious signal attenuation.

  10. The high price of anticancer drugs: origins, implications, barriers, solutions.

    PubMed

    Prasad, Vinay; De Jesús, Kevin; Mailankody, Sham

    2017-06-01

    Globally, annual spending on anticancer drugs is around US$100 billion, and is predicted to rise to $150 billion by 2020. In the USA, a novel anticancer drug routinely costs more than $100,000 per year of treatment. When adjusted for per capita spending power, however, drugs are most unaffordable in economically developing nations, such as India and China. Not only are launch prices high and rising, but individual drug prices are often escalated during exclusivity periods. High drug prices harm patients - often directly through increased out-of-pocket expenses, which reduce levels of patient compliance and lead to unfavourable outcomes - and harms society - by imposing cumulative price burdens that are unsustainable. Moreover, high drug prices are not readily explained by rational factors, including the extent of benefit patients are likely to derive, the novelty of the agents, or spending on research and development. Herein, we summarize the available empirical evidence on the costs of anticancer drugs, probe the origins and implications of these high costs, and discuss proposed solutions.

  11. Competitive interactions of ionic surfactants with salbutamol and bovine serum albumin: a molecular spectroscopy study with implications for salbutamol in food analysis.

    PubMed

    Zhang, Qiulan; Ni, Yongnian; Kokot, Serge

    2013-08-14

    The effect of ionic surfactants, sodium dodecyl sulfate (SDS) and N-cetyl-N,N,N-trimethylammonium bromide (CTAB), on the interaction between β-agonist salbutamol (SAL) and bovine serum albumin (BSA) was investigated with the use of fluorescence spectroscopy (FLS) and chemometrics methods [multivariate curve resolution-alternating least-squares (MCR-ALS) and parallel factor analysis algorithm (PARAFAC)]. It was found that the binding constant of SAL to BSA in the presence of CTAB was much larger than that without this ligand. The ligand/BSA stoichiometry was 4:1, that is, (CTAB)4-BSA, and was 2:1 with the ligand, that is, (SAL)2-BSA. These results were obtained from the concentration profiles extracted by MCR-ALS for all three reactants. Quantitative information on the complex CTAB-BSA-SAL species was obtained with the resolution of the excitation-emission fluorescence three-way data matrices by PARAFAC. This research has implications for the analysis of SAL in food and might be performed in laboratories associated with organizations such as the U.S. Food and Drug Administration (FDA) and the International Olympic Committee (IOC).

  12. 21 CFR 640.80 - Albumin (Human).

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... a sterile solution of the albumin derived from human plasma. (b) Source material. The source material of Albumin (Human) shall be plasma recovered from Whole Blood prepared as prescribed in §§ 640.1 through 640.5, or Source Plasma prepared as prescribed in §§ 640.60 through 640.76. (c) Additives in...

  13. 21 CFR 640.80 - Albumin (Human).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... a sterile solution of the albumin derived from human plasma. (b) Source material. The source material of Albumin (Human) shall be plasma recovered from Whole Blood prepared as prescribed in §§ 640.1 through 640.5, or Source Plasma prepared as prescribed in §§ 640.60 through 640.76. (c) Additives...

  14. 21 CFR 640.80 - Albumin (Human).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... a sterile solution of the albumin derived from human plasma. (b) Source material. The source material of Albumin (Human) shall be plasma recovered from Whole Blood prepared as prescribed in §§ 640.1 through 640.5, or Source Plasma prepared as prescribed in §§ 640.60 through 640.76. (c) Additives in...

  15. 21 CFR 640.80 - Albumin (Human).

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... a sterile solution of the albumin derived from human plasma. (b) Source material. The source material of Albumin (Human) shall be plasma recovered from Whole Blood prepared as prescribed in §§ 640.1 through 640.5, or Source Plasma prepared as prescribed in §§ 640.60 through 640.76. (c) Additives in...

  16. 21 CFR 640.80 - Albumin (Human).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... a sterile solution of the albumin derived from human plasma. (b) Source material. The source material of Albumin (Human) shall be plasma recovered from Whole Blood prepared as prescribed in §§ 640.1 through 640.5, or Source Plasma prepared as prescribed in §§ 640.60 through 640.76. (c) Additives in...

  17. Flocculation of diatomite by methylated egg albumin.

    PubMed

    Seki, Hideshi; Suzuki, Akira

    2003-07-01

    A common and inexpensive protein, egg albumin, was applied to the solid-liquid separation or flocculation of diatomite. Egg albumin was methylated in a 0.05 M HCl methyl alcohol solution at room temperature. About 90% of the carboxylic groups of egg albumin could be methylated within 24 h. The adsorption of egg albumin onto diatomite at pH 6.8 was remarkably enhanced by methylation. The adsorption constant of methylated egg albumin to diatomite at 30 degrees C was about 100-fold larger than that of native egg albumin; however, the adsorption constant of methylated egg albumin decreased to about 1/100 with temperature decreasing from 30 to 6 degrees C. The saturated adsorption amount of egg albumin was also increased by the methylation. The flocculating ability of methylated egg albumin was examined with a diatomite suspension at 6 and 30 degrees C in the pH range from pH 2 to 11. The diatomite suspension was effectively flocculated by the addition of small amounts of methylated egg albumin (only 0.5-1 wt% against diatomite) over a wide pH range from pH 3 to 10.

  18. Hydration of proteins: SAXS study of native and methoxy polyethyleneglycol (mPEG)-modified L-asparaginase and bovine serum albumin in mPEG solutions.

    PubMed

    Murthy, N S; Knox, J R

    2004-08-15

    Two mPEG-modified globular proteins [mPEG: methoxy poly(ethylene glycol)], and their native unmodified forms, were examined by small-angle x-ray scattering to evaluate the extent of their surface hydration. The effects of free and protein-bound mPEG on the hydration shell were modeled with discrete electron density profiles. We show that an mPEG-depleted layer can account for the decrease in the measured radius of gyration R(g) from 34.1 to 31.1 A in native L-asparaginase, and from 32.4 to 31.0 A in native bovine serum albumin (BSA) in mPEG-containing solvents. For mPEG-modified proteins in mPEG-free solvents, we attribute the observed increase in the R(g) over that of the native proteins (approximately 3% in L-asparaginase, and 10% in BSA) to the presence of mPEG on the protein surface. The R(g) of the mPEG-modified proteins in mPEG solutions generally decrease with mPEG concentration. Relative to the corresponding unmodified protein, this decrease in R(g) is much larger in BSA (from 35.6 to 31.2 A) but much smaller (from 34.9 to 34.3 A) in L-asparaginase. From these studies, the thickness of the hydration layer around L-asparaginase and BSA is estimated to be approximately 15 A. Exclusion of polyols from the protein domain could be related to the presence of the hydration shell around the protein.

  19. Albumin and multiple sclerosis.

    PubMed

    LeVine, Steven M

    2016-04-12

    Leakage of the blood-brain barrier (BBB) is a common pathological feature in multiple sclerosis (MS). Following a breach of the BBB, albumin, the most abundant protein in plasma, gains access to CNS tissue where it is exposed to an inflammatory milieu and tissue damage, e.g., demyelination. Once in the CNS, albumin can participate in protective mechanisms. For example, due to its high concentration and molecular properties, albumin becomes a target for oxidation and nitration reactions. Furthermore, albumin binds metals and heme thereby limiting their ability to produce reactive oxygen and reactive nitrogen species. Albumin also has the potential to worsen disease. Similar to pathogenic processes that occur during epilepsy, extravasated albumin could induce the expression of proinflammatory cytokines and affect the ability of astrocytes to maintain potassium homeostasis thereby possibly making neurons more vulnerable to glutamate exicitotoxicity, which is thought to be a pathogenic mechanism in MS. The albumin quotient, albumin in cerebrospinal fluid (CSF)/albumin in serum, is used as a measure of blood-CSF barrier dysfunction in MS, but it may be inaccurate since albumin levels in the CSF can be influenced by multiple factors including: 1) albumin becomes proteolytically cleaved during disease, 2) extravasated albumin is taken up by macrophages, microglia, and astrocytes, and 3) the location of BBB damage affects the entry of extravasated albumin into ventricular CSF. A discussion of the roles that albumin performs during MS is put forth.

  20. Evaluation of albumin structural modifications through cobalt-albumin binding (CAB) assay.

    PubMed

    Lee, Eunyoung; Eom, Ji-Eun; Jeon, Kyung-Hwa; Kim, Tae Hee; Kim, Eunnam; Jhon, Gil-Ja; Kwon, Youngjoo

    2014-03-01

    Human serum albumin (HSA) is the most abundant protein in the human body. HSA injections prepared by fractionating human blood have mainly covered the demand for albumin to treat hypoalbuminemia, the state of low concentration of albumin in blood. HSA in solution may exist in various forms such as monomers, oligomers, polymers, or as mixtures, and its conformational change and/or aggregation may occur easily. Considering these characteristics, there is a great chance of modification and polymer formation during the preparation processes of albumin products, especially injections. The albumin cobalt binding (ACB) test reported by Bar-Or et al. was originally designed to detect ischemia modified albumin (IMA), which contains the modified HSA N-terminal sequence by cleavage of the last two amino acids. In this study, we developed a cobalt albumin binding (CAB) assay to correct the flaws of the ACB test with improving the sensitivity and precision. The newly developed CAB assay easily detects albumin configuration alterations and may be able to be used in developing a quality control method for albumin and its pharmaceutical formulations including albumin injections.

  1. Influence of serum and albumin on the in vitro anandamide cytotoxicity toward C6 glioma cells assessed by the MTT cell viability assay: implications for the methodology of the MTT tests.

    PubMed

    Bilmin, Krzysztof; Kopczyńska, Beata; Grieb, Paweł

    2013-01-01

    Anandamide (AEA), an endogenous ligand of cannabinoid CB1 and CB2 receptors, which also binds transient receptor potential vanilloid type 1 receptor (TRPV1), has been shown to display substantial selective cytotoxicity toward some cancer cell lines in vitro, although the relevant data are not consistent. In the present study, we employed the MTT test to assess short-term cytotoxicity of AEA on C6 rat glioma cell culture. When anandamide was administered to the culture medium with foetal bovine serum (FBS), no cytotoxic effect was observed following 24 h exposure of the glioma cells to micromolar concentrations of AEA. However, if no serum was present in the medium, micro-to-submicromolar concentrations of AEA induced dose-dependent cytotoxicity clearly detectable after 24 h. Control experiments made it possible to exclude significant interference of serum with the MTT test per se. Bovine serum albumin mimicked the effect of FBS. We conclude that the apparent inhibition of short-term cytotoxicity of AEA toward C6 rat glioma cells in vitro is caused by binding AEA to serum proteins such as albumin. Taking into account that blood serum or albumin is practically always present in cell culture media, we discuss implications of binding substances to serum proteins for methodology and interpretation of in vitro cytotoxicity testing.

  2. Different effects of fluid loading with saline, gelatine, hydroxyethyl starch or albumin solutions on acid-base status in the critically ill.

    PubMed

    Spoelstra-de Man, Angélique M E; Smorenberg, Annemieke; Groeneveld, A B Johan

    2017-01-01

    Fluid administration in critically ill patients may affect acid-base balance. However, the effect of the fluid type used for resuscitation on acid-base balance remains controversial. We studied the effect of fluid resuscitation of normal saline and the colloids gelatine 4%, hydroxyethyl starch (HES) 6%, and albumin 5% on acid-base balance in 115 clinically hypovolemic critically ill patients during a 90 minute filling pressure-guided fluid challenge by a post-hoc analysis of a prospective randomized clinical trial. About 1700 mL was infused per patient in the saline and 1500 mL in each of the colloid groups (P<0.001). Overall, fluid loading slightly decreased pH (P<0.001) and there was no intergroup difference. This mildly metabolic acidifying effect was caused by a small increase in chloride concentration and decrease in strong ion difference in the saline- and HES-, and an increase in (uncorrected) anion gap in gelatine- and albumin-loaded patients, independent of lactate concentrations. In clinically hypovolemic, critically ill patients, fluid resuscitation by only 1500-1700 mL of normal saline, gelatine, HES or albumin, resulted in a small decrease in pH, irrespective of the type of fluid used. Therefore, a progressive metabolic acidosis, even with increased anion gap, should not be erroneously attributed to insufficient fluid resuscitation. ISRCTN Registry ISRCTN19023197.

  3. Steady-state and time-resolved fluorescence investigation of 2-pyridone and 3-pyridone in solution and their specific binding to human serum albumin

    NASA Astrophysics Data System (ADS)

    Abou-Zied, Osama K.; Al-Shihi, Othman I. K.

    2008-02-01

    2-pyridone (2Py) and 3-pyridone (3Py) were examined in different solvents and their binding to human serum albumin (HSA) was studied using steady-state spectroscopy and time-resolved fluorescence. Solvation of 2Py and 3Py by water was examined in binary mixtures of 1,4-dioxane and water. Analysis of the absorption and fluorescence data reveals the solvation of the hydrogen bonding center in 2Py by one water molecule and in 3Py by three water molecules. A zwitterionic tautomer of 3Py is formed in water and shows distinct absorption peaks from the absorption of the neutral tautomer. Fluorescence of 3Py was observed in polar solvents only, whereas 2Py is fluorescent in polar and nonpolar solvents. The absorption and fluorescence spectra of 2Py in different solvents indicate less solute-solvent interaction in nonpolar solvents. This observation was confirmed by the measured longer fluorescence lifetime of 2Py in cyclohexane compared to that in water. The mechanism of binding of 2Py and 3Py as probe ligands to HSA was investigated by following the intensity change and lifetime of HSA fluorescence after excitation at 280 nm. The presence of 2Py and 3Py causes a reduction in the fluorescence intensity and lifetime of HSA. This observation indicates that subdomain IIA binding site (Sudlow site I) is the host of the probes and the reduction in the fluorescence of HSA is due to energy transfer from the Trp-214 residue to the probe in each case. The distance between Trp-214 and each of the probes was calculated using Förster theory for energy transfer to be 1.99 nm for HSA/2Py and 2.44 nm for HSA/3Py. The shorter distance in the former complex indicates more efficient energy transfer than in the latter. This was confirmed by estimating the quenching rate constant (k q) in each complex. k q was calculated to be 1.44 x 10 12 M -1s -1 for HSA/2Py and 3.45 x 10 11 M -1s -1 for HSA/3Py. The calculated distances and the k q values indicate a static quenching mechanism operative in

  4. Observation of small cluster formation in concentrated monoclonal antibody solutions and its implications to solution viscosity.

    PubMed

    Yearley, Eric J; Godfrin, Paul D; Perevozchikova, Tatiana; Zhang, Hailiang; Falus, Peter; Porcar, Lionel; Nagao, Michihiro; Curtis, Joseph E; Gawande, Pradad; Taing, Rosalynn; Zarraga, Isidro E; Wagner, Norman J; Liu, Yun

    2014-04-15

    Monoclonal antibodies (mAbs) are a major class of biopharmaceuticals. It is hypothesized that some concentrated mAb solutions exhibit formation of a solution phase consisting of reversibly self-associated aggregates (or reversible clusters), which is speculated to be responsible for their distinct solution properties. Here, we report direct observation of reversible clusters in concentrated solutions of mAbs using neutron spin echo. Specifically, a stable mAb solution is studied across a transition from dispersed monomers in dilute solution to clustered states at more concentrated conditions, where clusters of a preferred size are observed. Once mAb clusters have formed, their size, in contrast to that observed in typical globular protein solutions, is observed to remain nearly constant over a wide range of concentrations. Our results not only conclusively establish a clear relationship between the undesirable high viscosity of some mAb solutions and the formation of reversible clusters with extended open structures, but also directly observe self-assembled mAb protein clusters of preferred small finite size similar to that in micelle formation that dominate the properties of concentrated mAb solutions.

  5. Kinetics of FcRn-mediated recycling of IgG and albumin in human: Pathophysiology and therapeutic implications using a simplified mechanism-based model

    PubMed Central

    Kim, Jonghan; Hayton, William L.; Robinson, John M.; Anderson, Clark L.

    2009-01-01

    The nonclassical MHC class-I molecule, FcRn, salvages both IgG and albumin from degradation. Here we introduce a mechanism-based kinetic model for human to quantify FcRn-mediated recycling of both ligands based on saturable kinetics and data from the literature using easily measurable plasma concentrations rather than unmeasurable endosomal concentrations. The FcRn-mediated fractional recycling rates of IgG and albumin were 142% and 44% of their fractional catabolic rates, respectively. Clearly, FcRn-mediated recycling is a major contributor to the high endogenous concentrations of these two important plasma proteins. While familial hypercatabolic hypoproteinemia is caused by complete FcRn deficiency, the hypercatabolic IgG deficiency of myotonic dystrophy could be explained, based on the kinetic analyses, by a normal number of FcRn with lowered affinity for IgG but normal affinity for albumin. A simulation study demonstrates that the plasma concentrations of IgG and albumin could be dynamically controlled by both FcRn-related and -unrelated parameters. PMID:17046328

  6. Physical chemistry of supersaturated solutions and implications for oral absorption.

    PubMed

    Taylor, Lynne S; Zhang, Geoff G Z

    2016-06-01

    Amorphous solid dispersion (ASD) formulations are widely used for delivery of poorly soluble drugs for dissolution enhancement and bioavailability improvement. When administered, ASDs often exhibit fast dissolution to yield supersaturated solutions. The physical chemistry of these supersaturated solutions is not well understood. This review will discuss the concepts of solubility, supersaturation, and the connection to membrane transport rate. Liquid-liquid phase separation (LLPS), which occurs when the amorphous solubility is exceeded, leading to solutions with interesting properties is extensively discussed as a phenomenon that is relevant to all enabling formulations. The multiple physical processes occurring during dissolution of the ASD and during oral absorption are analyzed. The beneficial reservoir effect of a system that has undergone LLPS is demonstrated, both experimentally and conceptually. It is believed that formulations that rapidly supersaturate and subsequently undergo LLPS, with maintenance of the supersaturation at this maximum value throughout the absorption process, i.e. those that exhibit "spring and plateau" behavior, will give superior performance in terms of absorption. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. An electrochemical albumin-sensing system utilizing microfluidic technology

    NASA Astrophysics Data System (ADS)

    Huang, Chao-June; Lu, Chiu-Chun; Lin, Thong-Yueh; Chou, Tse-Chuan; Lee, Gwo-Bin

    2007-04-01

    This paper reports an integrated microfluidic chip capable of detecting the concentration of albumin in urine by using an electrochemical method in an automatic format. The integrated microfluidic chip was fabricated by using microelectromechanical system techniques. The albumin detection was conducted by using the electrochemical sensing method, in which the albumin in urine was detected by measuring the difference of peak currents between a bare reference electrode and an albumin-adsorption electrode. To perform the detection of the albumin in an automatic format, pneumatic microvalves and micropumps were integrated onto the microfluidic chip. The albumin sample and interference mixture solutions such as homovanillic acid, dopamine, norepinephrine and epinephrine were first stored in one of the three reservoirs. Then the solution comprising the albumin sample and interference solutions was transported to pass through the detection zone utilizing the pneumatic micropump. Experimental data showed that the developed system can successfully detect the concentration of the albumin in the existence of interference materials. When compared with the traditional albumin-sensing method, smaller amounts of samples were required to perform faster detection by using the integrated microfluidic chip. Additionally, the microfluidic chip integrated with pneumatic micropumps and microvalves facilitates the transportation of the samples in an automatic mode with lesser human intervention. The development of the integrated microfluidic albumin-sensing system may be promising for biomedical applications. Preliminary results of the current paper were presented at the 2nd International Meeting on Microsensors and Microsystems 2006 (National Cheng Kung University, Tainan, Taiwan, 15-18 January).

  8. Segregation of solutes and gases in experimental freezing of dilute solutions: implications for natural glacial systems

    NASA Astrophysics Data System (ADS)

    Killawee, J. A.; Fairchild, I. J.; Tison, J.-L.; Janssens, L.; Lorrain, R.

    1998-12-01

    Low ionic strength waters containing significant calcium and bicarbonate are common in nature, but little literature exists on their behaviour during freezing. Modelling indicates that freezing-induced concentration of solutes (in a closed-system) would lead to progressive increase in calcite saturation index, despite rising partial pressure of CO 2 (PCO 2), but the consequences of CaCO 3 precipitation for the distribution of matter between solid, liquid, and gas phases required experimental investigation. We studied the effects of variations in the rate of advance of an ice-water interface and in the initial degree of saturation for calcite on the behaviour of the system. Downward growth of ice in a 24-cm diameter cylindrical vessel was achieved at a constant linear rate of 3 or 8 mm/h by the progressive cooling of an overlying alcohol reservoir, and the expansion of volume accommodated by regular water sampling through side ports, together with a small expansion chamber. Initial air-saturated solutions (initial PCO 2 in the range 10 -3 to 10 -3.2) were prepared to reflect a range from strongly undersaturated to supersaturated for calcite. Comparative blank experiments were run using deionized water. Ice growth led to enrichment in solutes at the ice-water interface and the creation of a diffusive boundary layer, calculated to be 0.6 mm thick, truncated below by convecting fluid. The first-formed ice (stage 1), was relatively solute-rich because of initial rapid ice nucleation. Where solutions were not strongly supersaturated for calcite this was followed by formation of a solute-poor (stage 2) ice. Ice-interface water segregation coefficients of stage 2 ice were calculated to be 0.0004-0.003 for various solute ions. The relative magnitude of segregation coefficients (Mg 2+ > Ca 2+ > Sr 2+) is attributed to interstitial incorporation (coupled with HCO 3-) in the ice lattice, and controlled by ion size. Air bubbles nucleated once nitrogen supersaturation had

  9. Effects of pH and metal ions on the conformation of bovine serum albumin in aqueous solution An attenuated total reflection (ATR) FTIR spectroscopic study

    NASA Astrophysics Data System (ADS)

    Qing, Huai; Yanlin, He; Fenlin, Sheng; Zuyi, Tao

    1996-11-01

    The Hummel-Dreyer gel permeation technique has been applied to investigate the binding of bovine serum albumin (BSA) with Zn 2+ and Cd 2+, and has provided evidence for the existence of two different types of binding sites in the BSA molecule. The effects of pH and the presence of metal ions Zn 2- and Cd 2+ on the conformation of BSA were investigated using ATR FTIR Spectroscopy. The results demonstrated that there were different conformational states in BSA at pH 5.0 and 9.0. Furthermore, we observed the spectral changes of BSA in the amide I region and major metal ion (Zn 2+ and Cd 2+) binding sites which were CO and CN groups of BSA.

  10. Protein Crystal Serum Albumin

    NASA Technical Reports Server (NTRS)

    1998-01-01

    As the most abundant protein in the circulatory system albumin contributes 80% to colloid osmotic blood pressure. Albumin is also chiefly responsible for the maintenance of blood pH. It is located in every tissue and bodily secretion, with extracellular protein comprising 60% of total albumin. Perhaps the most outstanding property of albumin is its ability to bind reversibly to an incredible variety of ligands. It is widely accepted in the pharmaceutical industry that the overall distribution, metabolism, and efficiency of many drugs are rendered ineffective because of their unusually high affinity for this abundant protein. An understanding of the chemistry of the various classes of pharmaceutical interactions with albumin can suggest new approaches to drug therapy and design. Principal Investigator: Dan Carter/New Century Pharmaceuticals

  11. Protein Crystal Serum Albumin

    NASA Technical Reports Server (NTRS)

    1998-01-01

    As the most abundant protein in the circulatory system albumin contributes 80% to colloid osmotic blood pressure. Albumin is also chiefly responsible for the maintenance of blood pH. It is located in every tissue and bodily secretion, with extracellular protein comprising 60% of total albumin. Perhaps the most outstanding property of albumin is its ability to bind reversibly to an incredible variety of ligands. It is widely accepted in the pharmaceutical industry that the overall distribution, metabolism, and efficiency of many drugs are rendered ineffective because of their unusually high affinity for this abundant protein. An understanding of the chemistry of the various classes of pharmaceutical interactions with albumin can suggest new approaches to drug therapy and design. Principal Investigator: Dan Carter/New Century Pharmaceuticals

  12. Experimental investigation of the serum albumin fascia microstructure

    NASA Astrophysics Data System (ADS)

    Buzoverya, M. E.; Shcherbak, Yu. P.; Shishpor, I. V.

    2012-09-01

    The results of theoretical and experimental investigation of biological liquids are reported. Structural effects observed in fascias are considered with account of the molecular features of albumin and the concept of supramolecular organization of polymers. It is revealed that the morphology of human serum albumin fascias depends on the concentration and quality of the solvent. It is shown that the water-salt fascias of albumin are more structured than water solutions with the same concentration.

  13. C-peptide and zinc delivery to erythrocytes requires the presence of albumin: implications in diabetes explored with a 3D-printed fluidic device.

    PubMed

    Liu, Yueli; Chen, Chengpeng; Summers, Suzanne; Medawala, Wathsala; Spence, Dana M

    2015-05-01

    People with type 1 diabetes (T1D) must administer insulin exogenously due to the destruction of their pancreatic β-cells. Endogenous insulin is stored in β-cell granules along with C-peptide, a 31 amino acid peptide that is secreted from these granules in amounts equal to insulin. Exogenous co-administration of C-peptide with insulin has proven to reduce diabetes-associated complications in animals and humans. The exact mechanism of C-peptide's beneficial effects after secretion from the β-cell granules is not completely understood, thus hindering its development as an exogenously administered hormone. Monitoring tissue-to-tissue communication using a 3D-printed microfluidic device revealed that zinc and C-peptide are being delivered to erythrocytes by albumin. Upon delivery, erythrocyte-derived ATP increased by >50%, as did endothelium-derived NO, which was measured downstream in the 3D-printed device. Our results suggest that hormone replacement therapy in diabetes may be improved by exogenous administration of a C-peptide ensemble that includes zinc and albumin.

  14. Comparison of the cryoprotective solutions based on human albumin vs. autologous plasma: its effect on cell recovery, clonogenic potential of peripheral blood hematopoietic progenitor cells and engraftment after autologous transplantation.

    PubMed

    Smagur, A; Mitrus, I; Ciomber, A; Panczyniak, K; Fidyk, W; Sadus-Wojciechowska, M; Holowiecki, J; Giebel, S

    2015-05-01

    Cryopreservation of peripheral blood hematopoietic progenitor/stem cells (PBPCs) requires the addition of cryoprotectant such as DMSO, often prediluted using human serum albumin solution (HSAS). The goal of our study was to verify whether the HSAS may be replaced by autologous plasma (AP) without negative impact on PBPCs quality and engraftment. AP usage is less expensive and allows performing cell preparation in a 'closed system', and hence to reduce the risk of product contamination. Peripheral blood progenitor cells from 18 patients were divided into two aliquots (500 μl) placed in separate vials, each containing 7·5% DMSO prediluted with 5% HSAS or AP. Post-thaw cell recovery and clonogenic potential was evaluated. During clinical part of the study, the impact of both cryoprotective solution on hematopoietic engraftment was evaluated in two cohorts (n = 26) matched for diagnosis, age and the number of transplanted CD34+ cells. The median recovery of nucleated cells and the number of colony-forming units did not differ between tested cryoprotective mixtures. For AP mixture, neither total protein nor albumin concentration of plasma correlated with cell recovery and clonogenic potential of the PBPCs after cryopreservation. In clinical evaluation, the median time to leucocyte recovery and reconstitution of neutrophils was comparable in both groups: 10 days. We did not observe either significant difference with regard to the time of platelet recovery (median: 15 days for AP vs. 16 for HSAS; P = 0·79). HSA in cryoprotective mixture may be replaced by AP without negative impact on cell recovery, clonogenic potential or engraftment. © 2015 International Society of Blood Transfusion.

  15. Structure of Serum Albumin

    NASA Technical Reports Server (NTRS)

    Carter, Daniel C.; Ho, Joseph X.

    1994-01-01

    Because of its availability, low cost, stability, and unusual ligand-binding properties, serum albumin has been one of the mst extensively studied and applied proteins in biochemistry. However, as a protein, albumin is far from typical, and the widespread interest in and application of albumin have not been balanced by an understanding of its molecular structure. Indeed, for more than 30 years structural information was surmised based solely on techniques such as hydrodynamics, low-angle X-ray scattering, and predictive methods.

  16. Albumin - blood (serum) test

    MedlinePlus

    ... Crohn disease (inflammation of the digestive tract) Low-protein diets Celiac disease (damage of the lining of the ... blood albumin may be due to: Dehydration High protein diet Having a tourniquet on for a long time ...

  17. Smartphone based point-of-care detector of urine albumin

    NASA Astrophysics Data System (ADS)

    Cmiel, Vratislav; Svoboda, Ondrej; Koscova, Pavlina; Provaznik, Ivo

    2016-03-01

    Albumin plays an important role in human body. Its changed level in urine may indicate serious kidney disorders. We present a new point-of-care solution for sensitive detection of urine albumin - the miniature optical adapter for iPhone with in-built optical filters and a sample slot. The adapter exploits smart-phone flash to generate excitation light and camera to measure the level of emitted light. Albumin Blue 580 is used as albumin reagent. The proposed light-weight adapter can be produced at low cost using a 3D printer. Thus, the miniaturized detector is easy to use out of lab.

  18. [Structure of fish serum albumins].

    PubMed

    Andreeva, A M

    2010-01-01

    Data are presented about the presence of serum albumins in fishes of different classes and orders inhabiting different ecological conditions, about structure of typical albumins and albumin-like proteins, and about the degree of homology of these proteins to mammalian albumins. There is shown a wide spectrum of structural diversity of albumins in Pisces due to their participation in osmotic, plastic, and transport functions under conditions of environment and of the organism internal media. Detection of similar motifs in the piscine and mammalian albumin genes allows uniting these genes into one superfamily and considering vertebrate albumins the homologous proteins.

  19. A New Application for Albumin Dialysis in Extracorporeal Organ Support: Characterization of a Putative Interaction Between Human Albumin and Proinflammatory Cytokines IL-6 and TNFα.

    PubMed

    Pfensig, Claudia; Dominik, Adrian; Borufka, Luise; Hinz, Michael; Stange, Jan; Eggert, Martin

    2016-04-01

    Albumin dialysis in extracorporeal organ support is often performed in the treatment of liver failure as it facilitates the removal of toxic components from the blood. Here, we describe a possible effect of albumin dialysis on proinflammatory cytokine levels in vitro. Initially, albumin samples were incubated with different amounts of cytokines and analyzed by enzyme-linked immunosorbent assay (ELISA). Analysis of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNFα) levels indicated that increased concentrations of albumin reduce the measureable amount of the respective cytokines. This led to the hypothesis that the used proinflammatory cytokines may interact with albumin. Size exclusion chromatography of albumin spiked with cytokines was carried out using high-performance liquid chromatography analysis. The corresponding fractions were evaluated by immunoblotting. We detected albumin and cytokines in the same fractions indicating an interaction of the small-sized cytokines IL-6 and TNFα with the larger-sized albumin. Finally, a two-compartment albumin dialysis in vitro model was used to analyze the effect of albumin on proinflammatory cytokines in the recirculation circuit during 6-h treatment. These in vitro albumin dialysis experiments indicated a significant decrease of IL-6, but not of TNFα, when albumin was added to the dialysate solution. Taken together, we were able to show a putative in vitro interaction of human albumin with the proinflammatory cytokine IL-6, but with less evidence for TNFα, and demonstrated an additional application for albumin dialysis in liver support therapy where IL-6 removal might be indicated.

  20. Extraction and characterization of chickpea (Cicer arietinum) albumin and globulin.

    PubMed

    Liu, L H; Hung, T V; Bennett, L

    2008-06-01

    Albumin and globulin fractions of 1 Desi and 2 Kabuli varieties of chickpeas (Cicer arietinum) were extracted with water and salt solutions (K(2)SO(4) and NaCl). The extractable yields and particularly the albumin-globulin ratio varied greatly with the extraction medium and chickpea variety. Depending on the procedure employed, albumin could be extracted as a major fraction of chickpea proteins. Higher levels of essential amino acids and sulfur containing amino acids were found in albumins than in globulins of all chickpeas investigated. The common structural characteristics of both Kabuli and Desi chickpea albumins and globulins were clearly identified by densitometric profiles of their sodium dodecyl sulfate polyacrylamide gel patterns. Albumins contained subunits with higher molecular weights than those of globulins. The in vitro digestibility of the chickpea proteins by papain, pepsin, chymotrypsin, and trypsin indicated that globulins were more susceptible to proteolytic hydrolysis.

  1. Binding of Sulpiride to Seric Albumins

    PubMed Central

    da Silva Fragoso, Viviane Muniz; de Morais Coura, Carla Patrícia; Hoppe, Luanda Yanaan; Soares, Marília Amável Gomes; Silva, Dilson; Cortez, Celia Martins

    2016-01-01

    The aim of this work was to study the interaction of sulpiride with human serum albumin (HSA) and bovine serum albumin (BSA) through the fluorescence quenching technique. As sulpiride molecules emit fluorescence, we have developed a simple mathematical model to discriminate the quencher fluorescence from the albumin fluorescence in the solution where they interact. Sulpiride is an antipsychotic used in the treatment of several psychiatric disorders. We selectively excited the fluorescence of tryptophan residues with 290 nm wavelength and observed the quenching by titrating HSA and BSA solutions with sulpiride. Stern-Volmer graphs were plotted and quenching constants were estimated. Results showed that sulpiride form complexes with both albumins. Estimated association constants for the interaction sulpiride–HSA were 2.20 (±0.08) × 104 M−1, at 37 °C, and 5.46 (±0.20) × 104 M−1, at 25 °C. Those for the interaction sulpiride-BSA are 0.44 (±0.01) × 104 M−1, at 37 °C and 2.17 (±0.04) × 104 M−1, at 25 °C. The quenching intensity of BSA, which contains two tryptophan residues in the peptide chain, was found to be higher than that of HSA, what suggests that the primary binding site for sulpiride in albumin should be located next to the sub domain IB of the protein structure. PMID:26742031

  2. Binding of Sulpiride to Seric Albumins.

    PubMed

    da Silva Fragoso, Viviane Muniz; de Morais Coura, Carla Patrícia; Hoppe, Luanda Yanaan; Soares, Marília Amável Gomes; Silva, Dilson; Cortez, Celia Martins

    2016-01-04

    The aim of this work was to study the interaction of sulpiride with human serum albumin (HSA) and bovine serum albumin (BSA) through the fluorescence quenching technique. As sulpiride molecules emit fluorescence, we have developed a simple mathematical model to discriminate the quencher fluorescence from the albumin fluorescence in the solution where they interact. Sulpiride is an antipsychotic used in the treatment of several psychiatric disorders. We selectively excited the fluorescence of tryptophan residues with 290 nm wavelength and observed the quenching by titrating HSA and BSA solutions with sulpiride. Stern-Volmer graphs were plotted and quenching constants were estimated. Results showed that sulpiride form complexes with both albumins. Estimated association constants for the interaction sulpiride-HSA were 2.20 (±0.08) × 10⁴ M(-1), at 37 °C, and 5.46 (±0.20) × 10⁴ M(-1), at 25 °C. Those for the interaction sulpiride-BSA are 0.44 (±0.01) × 10⁴ M(-1), at 37 °C and 2.17 (±0.04) × 10⁴ M(-1), at 25 °C. The quenching intensity of BSA, which contains two tryptophan residues in the peptide chain, was found to be higher than that of HSA, what suggests that the primary binding site for sulpiride in albumin should be located next to the sub domain IB of the protein structure.

  3. Serum albumins - unusual allergens

    PubMed Central

    Chruszcz, Maksymilian; Mikolajczak, Katarzyna; Mank, Nicholas; Majorek, Karolina A.; Porebski, Przemyslaw J.; Minor, Wladek

    2015-01-01

    Background Albumins are multifunctional proteins present in the blood serum of animals. They can bind and transport a wide variety of ligands which they accommodate due to their conformational flexibility. Serum albumins are highly conserved both in amino acid sequence and three-dimensional structure. Several mammalian and avian serum albumins (SAs) are also allergens. Sensitization to one of the SAs coupled with the high degree of conservation between SAs may result in cross-reactive antibodies in allergic individuals. Sensitivity to SA generally begins with exposure to an aeroallergen, which can then lead to cross-sensitization to serum albumins present in food. Scope of Review This review focuses on the allergenicity of SAs presented in a structural context. Major Conclusions SA allergenicity is unusual taking into account the high sequence identity and similarity between SA from different species and human serum albumin. Cross-reactivity of human antibodies towards different SAs is one of the most important characteristics of these allergens. General Significance Establishing a relationship between sequence and structure of different SAs and their interactions with antibodies is crucial for understanding the mechanisms of cross-sensitization of atopic individuals. Structural information can also lead to better design and production of recombinant SAs to replace natural proteins in allergy testing and desensitization. Therefore, structural analyses are important for diagnostic and treatment purposes. PMID:23811341

  4. Trauma-hemorrhagic shock mesenteric lymph from rat contains a modified form of albumin that is implicated in endothelial cell toxicity.

    PubMed

    Kaiser, Vicki L; Sifri, Ziad C; Dikdan, George S; Berezina, Tamara; Zaets, Sergey; Lu, Qi; Xu, Da-Zhong; Deitch, Edwin A

    2005-05-01

    It has been proposed that factors originating from the gut after severe trauma/shock are introduced into the systemic circulation through the mesenteric lymphatics and are responsible for the cellular injury and inflammation that culminates in acute multiple organ dysfunction syndrome (MODS). Indeed, it has been shown that lymph collected from shocked but not sham-shocked animals causes endothelial cell death, neutrophil activation, and bone marrow (BM) colony growth suppression in vitro. In an attempt to isolate the factor(s) in lymph responsible for endothelial cell toxicity, lymph from shock and sham animals was fractionated by solid phase extraction (SPE) and ion exchange chromatography (IEX). The separation of shock lymph by both methodologies yielded two fractions having major detectable toxicity to endothelial cells, whereas no toxicity was detected from sham lymph separations by either method. Subsequent analysis of each SPE toxic fraction by gel electrophoresis and mass spectrometry suggests the toxicity is associated with a modified form of rat serum albumin (mod-RSA) and multiple lipid-based factors. Therefore, we have been able to demonstrate by two different separation techniques that shock lymph contains two or more factors that may account for the toxicity to endothelial cells. Further investigations are needed to determine the type of RSA modification and the identity of the lipid factors and their role in MODS.

  5. Associations of amides with bovine serum albumin (BSA) in D 2O, urea and guanidine hydrochloride (Gu·HCl) solutions - 1H NMR study

    NASA Astrophysics Data System (ADS)

    Michnik, Anna; Sulkowska, Anna

    1995-03-01

    The hydrophobic interaction between apolar fragments of denaturants and the hydrophobic pockets of protein is the most probable mechanism of denaturation for amides. However the low-affinity hydrophobic complexes are stabilised by hydrogen bonds engaging oxygen of carbonyl group and in less extend hydrogen of imino group. Amides are poorly bound by denatured BSA and the character of complexes for amides with branched chains changes in urea and guanidine hydrochloride solutions.

  6. Binding of furosemide to albumin isolated from human fetal and adult serum.

    PubMed

    Viani, A; Cappiello, M; Silvestri, D; Pacifici, G M

    1991-01-01

    Albumin was isolated from pooled fetal serum from 58 placentas obtained at normal delivery at term and from pooled adult plasma from 8 individuals. Albumin isolation was carried out by means of PEG precipitation followed by ion-exchange chromatography on DEAE-Sephadex A 50 and then on SP-Sephadex C 50. The electrophoresis on SDS-polyacrylamide gels showed only one spot that comigrated with commercial human albumin. Binding to albumin was measured by equilibrium dialysis of an aliquot of albumin solution (0.7 ml) against the same volume of 0.13 M sodium orthophosphate buffer (pH 7.4). At a total concentration of 2 micrograms/ml (therapeutic range), the unbound fraction of furosemide was 2.71% (fetal albumin) and 2.51% (adult albumin). Two classes of binding sites for furosemide were observed in fetal and adult albumin. The number of binding sites (moles of furosemide per mole of albumin) was 1.22 (fetal albumin) and 1.58 (adult albumin) for the high-affinity site and 2.97 (fetal albumin) and 3.25 (adult albumin) for the low-affinity site. The association constants (M-1) were 3.1 X 10(4) (fetal albumin) and 2.6 X 10(4) (adult albumin) for the high-affinity set of sites and 0.83 X 10(4) (fetal albumin) and 1.0 X 10(4) (adult albumin) low-affinity site. The displacement of furosemide from albumin was studied with therapeutic concentrations of several drugs. Valproic acid, salicylic acid, azapropazone and tolbutamide had the highest displacing effects which were significantly higher with fetal than with adult albumin.

  7. [Properties and clinical implications of middle molecular weight low substitution hydroxyethyl starch solution].

    PubMed

    Kotake, Yoshifumi

    2014-02-01

    In this review article, the properties and clinical implications of middle molecular weight low substitution hydroxyethyl starch (HES) solution are summarized. This preparation shows larger volume effect and longer duration compared to the currently available low-molecular weight HES solution and will be available in the near future in Japan. Effects on renal function and coagulation system are supposedly dependent on the persistence of larger HES molecule in the body and this middle molecular weight low substitution HES preparation may be advantageous to the older HES preparation due to its rapid metabolism. This preparation has been successfully used in the goal-directed fluid management in the early recovery program after surgery and will offer several advantages in fluid management when introduced in Japan.

  8. 3200 PHAETHON: IMPLICATIONS OF A UNIQUE POLE SOLUTION AND THERMAL MODELING

    NASA Astrophysics Data System (ADS)

    Ansdell, Megan; Meech, K. J.; Bauer, J.; Hainaut, O. R.; Dundon, L.; Schorghofer, N.

    2013-10-01

    3200 Phaethon is the parent body of the Geminid meteor stream, yet its activity mechanism remains debated. A pole solution is an important physical parameter used in thermal modeling for assessing the survival of volatiles and thus potential activity mechanisms forming the Geminids. We will present time-series photometry of 3200 Phaethon obtained on 15 nights from 1994 to 2004 primarily using the Tek2K CCD camera on the University of Hawaii 2.2m telescope. The data were obtained at four distinct ecliptic longitudes, allowing us to derive a pole solution of λ=98.4° and β=-15.7° with a refined rotation period of P=3.60277+/-0.00001 hours using the light-curve inversion software convexin. We applied the criteria presented in Durech et al. 2009 for using convexin to derive unique and accurate pole solutions with limited photometry datasets. Additionally, we input our pole solution into a semi-implicit, one-dimensional thermal model to create maximum, minimum, and mean surface temperature maps as a function of latitude on the surface of 3200 Phaethon. We will discuss the implications of these surface temperature variations and also present results form deep searches for faint residual dust in the orbit of 3200 Phaethon.

  9. Piezoelectric quartz crystal impedance study of the Pb2+-induced precipitation of bovine serum albumin and its dissolution with EDTA in an aqueous solution.

    PubMed

    Yuan, Yu; Cai, Yan; Xie, Qingji; Yao, Shouzhuo

    2002-07-01

    The piezoelectric quartz crystal impedance technique (QCI) was employed to monitor in situ the Pb2+-induced precipitation of BSA onto a gold electrode and the precipitate dissolution with EDTA in an aqueous solution. The critical precipitation concentration of Pb2+, at which the resonant frequency decreased significantly, was estimated to be 4.78 x 10(-4) mol/L. The saturated adherence of the precipitate on the electrode was observed when the concentration of Pb2+ was greater than 7.53 x 10(-2) mol/L. The frequency response was mainly caused by the mass effect of the precipitate adherence to the electrode, rather than the changes in the physico-chemical properties of the contacting liquid. An excess addition of Na2EDTA after the Pb2+-BSA dissolution led to new precipitation, probably due to the formation of an EDTA precipitate in this medium (pH approximately 3). The pH effect on the response of the resonant frequency was analyzed by using the sum of two exponential functions. A larger frequency response occurred at a pH greater than pI. These findings have been reasonably explained. Also, a decrease in the concentration of the background electrolyte increased the frequency response.

  10. Parents' perceptions of causes of and solutions for school violence: implications for policy.

    PubMed

    Bliss, Melanie J; Emshoff, James; Buck, Chad A; Cook, Sarah L

    2006-05-01

    This study explores perceptions of causes of and solutions for school violence in a sample of 202 parents interviewed in the wake of nationally publicized school shootings. We also investigate the effects the school shootings had on children, parents' perceptions regarding firearms, and changes in parenting behavior. Parents exhibited strong support for almost all proposed causes and solutions, and we address their desire for immediate and often invasive interventions to prevent future violence. We contrast parents' perceptions with their own parenting behaviors and with literature on effective interventions. Results are discussed within the context of policy implications.Editors' Strategic Implications: Parents' perceptions and behaviors are frequently influenced by history effects. The national attention received by school shootings provided an opportunity for exploration of those perceptions and self-reported behaviors. The authors provide evidence from timely surveys that parents struggle with identifying causal factors that may contribute to school violence and consequently support a myriad of strategies for intervention including very invasive environmental preventive strategies. The findings suggest that social scientists should play a proactive role in translating research-supported preventive strategies to effective replications in the community and make research available in formats that are available and comprehensible by the lay public.

  11. Intrarenal distribution of inorganic mercury and albumin after coadministration

    SciTech Connect

    Zalups, R.K. ); Barfuss, D.W. )

    1993-01-01

    The renal disposition and the intrarenal distribution of albumin and mercury were studied simultaneously in rats co-injected with a 0.5-[mu]mol/kg dose of albumin and a 0.25-[mu]mol/kg dose of inorganic mercury at 2, 5, 30, and 180 min after injection. These studies were carried out to test the hypothesis that one of the mechanisms involved in the renal tubular uptake of inorganic mercury is cotransport with albumin. By the end of the first 2 min after injection, the ratio of inorganic mercury to albumin in the renal cortex and outer strip of the outer medulla was approximately 2.6 and 1.6, respectively. Both the cortex and outer stripe contain segments of the proximal tubule, and it is these segments that have been shown to be principally involved in the renal tubular uptake of both albumin and inorganic mercury. The ration increased slightly in these two zones after 5 and 20 min after injection. These data demonstrate that there is a relatively close relationship in the renal content of inorganic mercury and albumin. However, the ratios are significantly greater than the ratio of inorganic mercury of albumin in the injection solution, which was 0.5. After 180 min following co-injection, the ratio increased to about 38 in the cortex and 15 in the outer stripe. This increase in the ratio is probably related to the metabolism of albumin. Based on the ratios of inorganic mercury to albumin in the renal cortex and outer stripe of the outer medulla, it appears that some proximal tubular uptake of inorganic mercury occurs by mechanisms other than endocytotic cotransport of inorganic mercury with albumin. However, since the ratios were small during the early times after injection, cotransport of inorganic mercury with albumin cannot be excluded as one of the mechanisms involved in the proximal tubular uptake of inorganic mercury. 32 refs., 12 figs., 4 tabs.

  12. Molecular spectroscopic study on the interaction of tetracyclines with serum albumins.

    PubMed

    Bi, Shuyun; Song, Daqian; Tian, Yuan; Zhou, Xin; Liu, Zhongying; Zhang, Hanqi

    2005-02-01

    A molecular spectroscopic investigation of the interaction between tetracyclines antibiotics and human serum albumin or bovine serum albumin was reported. The influences of some metal ions on the interaction were also studied. When tetracyclines drugs were added into the solution containing serum albumins, the fluorescence intensity of serum albumins decreased with the increasing of the drugs concentrations, which is due to the formation of new non-fluorescence complexes of drug-serum albumin. The tetracyclines acted as quenchers and quenched the fluorescence of the serum albumins. The binding constants and the number of the binding sites of the reaction of tetracyclines and serum albumins were obtained. The main sorts of acting force between the drugs and serum albumins were found and the action distances and the energy transfer efficiencies between donor-acceptor were calculated based on the Foster energy transference.

  13. Molecular spectroscopic study on the interaction of tetracyclines with serum albumins

    NASA Astrophysics Data System (ADS)

    Bi, Shuyun; Song, Daqian; Tian, Yuan; Zhou, Xin; Liu, Zhongying; Zhang, Hanqi

    2005-02-01

    A molecular spectroscopic investigation of the interaction between tetracyclines antibiotics and human serum albumin or bovine serum albumin was reported. The influences of some metal ions on the interaction were also studied. When tetracyclines drugs were added into the solution containing serum albumins, the fluorescence intensity of serum albumins decreased with the increasing of the drugs concentrations, which is due to the formation of new non-fluorescence complexes of drug-serum albumin. The tetracyclines acted as quenchers and quenched the fluorescence of the serum albumins. The binding constants and the number of the binding sites of the reaction of tetracyclines and serum albumins were obtained. The main sorts of acting force between the drugs and serum albumins were found and the action distances and the energy transfer efficiencies between donor-acceptor were calculated based on the Föster energy transference.

  14. Structures of bovine, equine and leporine serum albumin.

    PubMed

    Bujacz, Anna

    2012-10-01

    Serum albumin first appeared in early vertebrates and is present in the plasma of all mammals. Its canonical structure supported by a conserved set of disulfide bridges is maintained in all mammalian serum albumins and any changes in sequence are highly correlated with evolution of the species. Previous structural investigations of mammalian serum albumins have only concentrated on human serum albumin (HSA), most likely as a consequence of crystallization and diffraction difficulties. Here, the crystal structures of serum albumins isolated from bovine, equine and leporine blood plasma are reported. The structure of bovine serum albumin (BSA) was determined at 2.47 Å resolution, two crystal structures of equine serum albumin (ESA) were determined at resolutions of 2.32 and 2.04 Å, and that of leporine serum albumin (LSA) was determined at 2.27 Å resolution. These structures were compared in detail with the structure of HSA. The ligand-binding pockets in BSA, ESA and LSA revealed different amino-acid compositions and conformations in comparison to HSA in some cases; however, much more significant differences were observed on the surface of the molecules. BSA, which is one of the most extensively utilized proteins in laboratory practice and is used as an HSA substitute in many experiments, exhibits only 75.8% identity compared with HSA. The higher resolution crystal structure of ESA highlights the binding properties of this protein because it includes several bound compounds from the crystallization solution that provide additional structural information about potential ligand-binding pockets.

  15. Chicken albumin exhibits natural resistance to glycation.

    PubMed

    Zuck, Jessica; Borges, Chad R; Braun, Eldon J; Sweazea, Karen L

    2017-01-01

    Glycation of proteins and subsequent production of advanced glycation end products (AGEs) is a major contributor to the pathophysiology of diabetes. The objective of the present study was to compare the glycation of avian and human serum albumin to elucidate the mechanisms by which protein glycation in birds is prevented in the presence of naturally high plasma glucose concentrations. Solutions of purified chicken and human serum albumin (CSA and HSA) were prepared with four different glucose concentrations (0, 5.56, 11.1, and 22.2mM) and incubated at three temperatures (37.0, 39.8, and 41.4°C) for seven days. The solutions were sampled on Days 0, 3, and 7 and analyzed by liquid chromatography-electrospray ionization-mass spectrometry for the presence of glycated albumin. Four-way repeated measures ANOVA (p=0.032) indicate that all independent variables (albumin type, glucose concentration, temperature and time) interacted to affect the degree of glycation. With increasing glucose concentration, the glycation of both HSA and CSA increased with time at all temperatures. In addition, HSA was glycated to a greater extent than CSA at the two higher glucose concentrations for all temperature conditions. Glycation was elevated with increasing temperatures for HSA but not CSA. The results suggest an inherent difference between human and chicken albumin that contributes to the observed differences in glycation. Further research is needed to characterize this inherent difference in an effort to elucidate mechanisms by which avian plasma protein is glycated to a lesser degree than that of mammals (humans).

  16. A new application of micellar liquid chromatography in the determination of free ampicillin concentration in the drug-human serum albumin standard solution in comparison with the adsorption method.

    PubMed

    Stępnik, Katarzyna E; Malinowska, Irena; Maciejewska, Małgorzata

    2016-06-01

    The determination of free drug concentration is a very important issue in the field of pharmacology because only the unbound drug fraction can achieve a pharmacological effect. Due to the ability to solubilize many different compounds in micellar aggregates, micellar liquid chromatography (MLC) can be used for direct determination of free drug concentration. Proteins are not retained on the stationary phase probably due to the formation of protein - surfactant complexes which are excluded from the pores of stationary phase. The micellar method is simple and fast. It does not require any pre-preparation of the tested samples for analysis. The main aim of this paper is to demonstrate a completely new applicability of the analytical use of MLC concerning the determination of free drug concentration in the standard solution of human serum albumin. The well-known adsorption method using RP-HPLC and the spectrophotometric technique was applied as the reference method. The results show that the free drug concentration value obtained in the MLC system (based on the RP-8 stationary phase and CTAB) is similar to that obtained by the adsorption method: both RP-HPLC (95.83μgmL(-1), 79.86% of free form) and spectrophotometry (95.71μgmL(-1), 79.76%). In the MLC the free drug concentration was 93.98μgmL(-1) (78.3%). This indicates that the obtained results are within the analytical range of % of free ampicillin fraction and the MLC with direct sample injection can be treated like a promising method for the determination of free drug concentration.

  17. Influence of salt on colloidal lithography of albumin.

    PubMed

    Geng, D L; Miao, Y H; Helseth, L E

    2007-07-31

    We investigate the influence of salt on colloidal lithography of biomolecular patterns. Albumin labeled with fluorescein isothiocyanate (FITC) was adsorbed on polyelectrolyte-coated glass substrates covered by negatively charged colloids using fluorescence microscopy. After removing the colloids, a well-defined albumin pattern remains, and we study how the pattern changes upon adding salt to the protein solution. The proposed method is simple and cheap and can be used to create stable one- and two-dimensional biomolecular arrays.

  18. Albumin replacement in patients with severe sepsis or septic shock.

    PubMed

    Caironi, Pietro; Tognoni, Gianni; Masson, Serge; Fumagalli, Roberto; Pesenti, Antonio; Romero, Marilena; Fanizza, Caterina; Caspani, Luisa; Faenza, Stefano; Grasselli, Giacomo; Iapichino, Gaetano; Antonelli, Massimo; Parrini, Vieri; Fiore, Gilberto; Latini, Roberto; Gattinoni, Luciano

    2014-04-10

    Although previous studies have suggested the potential advantages of albumin administration in patients with severe sepsis, its efficacy has not been fully established. In this multicenter, open-label trial, we randomly assigned 1818 patients with severe sepsis, in 100 intensive care units (ICUs), to receive either 20% albumin and crystalloid solution or crystalloid solution alone. In the albumin group, the target serum albumin concentration was 30 g per liter or more until discharge from the ICU or 28 days after randomization. The primary outcome was death from any cause at 28 days. Secondary outcomes were death from any cause at 90 days, the number of patients with organ dysfunction and the degree of dysfunction, and length of stay in the ICU and the hospital. During the first 7 days, patients in the albumin group, as compared with those in the crystalloid group, had a higher mean arterial pressure (P=0.03) and lower net fluid balance (P<0.001). The total daily amount of administered fluid did not differ significantly between the two groups (P=0.10). At 28 days, 285 of 895 patients (31.8%) in the albumin group and 288 of 900 (32.0%) in the crystalloid group had died (relative risk in the albumin group, 1.00; 95% confidence interval [CI], 0.87 to 1.14; P=0.94). At 90 days, 365 of 888 patients (41.1%) in the albumin group and 389 of 893 (43.6%) in the crystalloid group had died (relative risk, 0.94; 95% CI, 0.85 to 1.05; P=0.29). No significant differences in other secondary outcomes were observed between the two groups. In patients with severe sepsis, albumin replacement in addition to crystalloids, as compared with crystalloids alone, did not improve the rate of survival at 28 and 90 days. (Funded by the Italian Medicines Agency; ALBIOS ClinicalTrials.gov number, NCT00707122.).

  19. Chromatographic and traditional albumin isotherms on cellulose: a model for wound protein adsorption on modified cotton.

    PubMed

    Edwards, J Vincent; Castro, Nathan J; Condon, Brian; Costable, Carmen; Goheen, Steven C

    2012-05-01

    Albumin is the most abundant protein found in healing wounds. Traditional and chromatographic protein isotherms of albumin binding on modified cotton fibers are useful in understanding albumin binding to cellulose wound dressings. An important consideration in the design of cellulosic wound dressings is adsorption and accumulation of proteins like albumin at the solid-liquid interface of the biological fluid and wound dressing fiber. To better understand the effect of fiber charge and molecular modifications in cellulose-containing fibers on the binding of serum albumin as observed in protease sequestrant dressings, albumin binding to modified cotton fibers was compared with traditional and chromatographic isotherms. Modified cotton including carboxymethylated, citrate-crosslinked, dialdehyde and phosphorylated cotton, which sequester elastase and collagenase, were compared for their albumin binding isotherms. Albumin isotherms on citrate-cellulose, cross-linked cotton demonstrated a two-fold increased binding affinity over untreated cotton. A comparison of albumin binding between traditional, solution isotherms and chromatographic isotherms on modified cellulose yielded similar equilibrium constants. Application of the binding affinity of albumin obtained in the in vitro protein isotherm to the in vivo wound dressing uptake of the protein is discussed. The chromatographic approach to assessment of albumin isotherms on modified cellulose offers a more rapid approach to evaluating protein binding on modified cellulose over traditional solution approaches.

  20. Implications of new GALLEX results for the Mikheyev-Smirnov-Wolfenstein solution of the solar neutrino problem

    NASA Technical Reports Server (NTRS)

    Gelb, James M.; Kwong, Waikwok; Rosen, S. P.

    1992-01-01

    We compare the implications for Be-7 and pp neutrinos of the two Mikheyev-Smirnov-Wolfenstein fits to the new GALLEX solar neutrino measurements. Small-mixing-angle solutions tend to suppress the former as electron neutrinos, but not the latter, and large-angle solutions tend to reduce both by about a factor of two. The consequences for BOREXINO and similar solar neutrino-electron scattering experiments are discussed.

  1. Aldolase activity of serum albumins.

    PubMed

    Benedetti, Fabio; Berti, Federico; Bidoggia, Silvia

    2011-06-21

    Bovine and human serum albumins catalyze the aldol reaction of aromatic aldehyedes and acetone, with saturation kinetics and moderate and opposite enantioselectivity. The reaction occurs at the binding site in domain IIa, and is inhibited by warfarin. Kinetic data are consistent with an enamine mechanism. The activity is conserved in a 103 aminoacid peptide derived from the albumin sequence.

  2. Albumin synthesis in surgical patients.

    PubMed

    Hülshoff, Ansgar; Schricker, Thomas; Elgendy, Hamed; Hatzakorzian, Roupen; Lattermann, Ralph

    2013-05-01

    Albumin plasma concentrations are being used as indicators of nutritional status and hepatic function based on the assumption that plasma levels reflect the rate of albumin synthesis. However, it has been shown that albumin levels are not reliable markers of albumin synthesis under a variety of clinical conditions including inflammation, malnutrition, diabetes mellitus, liver disease, and surgical tissue trauma. To date, only a few studies have measured albumin synthesis in surgical and critically ill patients. This review summarizes the findings from these studies, which used different tracer methodology in various surgical or critically ill patient populations. The results indicate that the fractional synthesis rate of albumin appears to decrease during surgery, followed by an increase during the postoperative phase. In the early postoperative phase, albumin fractional synthesis rate can be stimulated by perioperative nutrition, if enough amino acids are being provided and if nutrition is being initiated before the operation. The physiologic meaning of albumin synthesis after surgery, however, still needs to be further clarified.

  3. Adsorption of egg albumin onto methylated yeast biomass.

    PubMed

    Seki, Hideshi; Suzuki, Akira; Maruyama, Hideo

    2004-02-15

    A new biosorbent, methylated yeast (MeYE), was prepared for the adsorptive separation of proteins from aqueous solutions. Yeast was methylated in a 0.1 M HCl methyl alcohol solution at room temperature. About 80% of the carboxylic groups of yeast could be methylated within 9 h. The adsorption of egg albumin onto MeYE was studied to evaluate the protein adsorption ability of MeYE. At near neutral pH, egg albumin was scarcely adsorbed onto unmethylated yeast and the adsorbed amount of egg albumin increased with increasing methylation degree. The amount of egg albumin adsorbed onto MeYE increased with increasing pH from 4 to 7 and steeply decreased above pH 7. The Langmuir isotherm was applied to determine the apparent adsorption constant and the saturated adsorbed amount of egg albumin on MeYE. Both the apparent adsorption constant and the saturated adsorbed amount increased with the degree of methylation. The saturated adsorbed amount of egg albumin onto MeYE having methylation degree 77% was 8.41 x 10(-6) mol g(-1) or 0.378 gg(-1) at near neutral pH.

  4. Albumin administration for fluid resuscitation in burn patients: A systematic review and meta-analysis.

    PubMed

    Eljaiek, Roberto; Heylbroeck, Christophe; Dubois, Marc-Jacques

    2017-02-01

    The objective was to systematically review the literature summarizing the effect on mortality of albumin compared to non-albumin solutions during the fluid resuscitation phase of burn injured patients. We searched MEDLINE, EMBASE and CENTRAL and the content of two leading journals in burn care, Burns and Journal of Burn Care and Research. Two reviewers independently selected randomized controlled trials comparing albumin vs. non-albumin solutions for the acute resuscitation of patients with >20% body surface area involvement. Reviewers abstracted data independently and assessed methodological quality of the included trials using predefined criteria. A random effects model was used to assess mortality. We identified 164 trials of which, 4 trials involving 140 patients met our inclusion criteria. Overall, the methodological quality of the included trials was fair. We did not find a significant benefit of albumin solutions as resuscitation fluid on mortality in burn patients (relative risk (RR) 1.6; 95% confidence interval (CI), 0.63-4.08). Total volume of fluid infusion during the phase of resuscitation was lower in patients receiving albumin containing solution -1.00ml/kg/%TBSA (total body surface area) (95% CI, -1.42 to -0.58). The pooled estimate demonstrated a neutral effect on mortality in burn patients resuscitated acutely with albumin solutions. Due to limited evidence and uncertainty, an adequately powered, high quality trial could be required to assess the impact of albumin solutions on mortality in burn patients. Copyright © 2016 Elsevier Ltd and ISBI. All rights reserved.

  5. The role of non-verbal behaviour in racial disparities in health care: implications and solutions.

    PubMed

    Levine, Cynthia S; Ambady, Nalini

    2013-09-01

    People from racial minority backgrounds report less trust in their doctors and have poorer health outcomes. Although these deficiencies have multiple roots, one important set of explanations involves racial bias, which may be non-conscious, on the part of providers, and minority patients' fears that they will be treated in a biased way. Here, we focus on one mechanism by which this bias may be communicated and reinforced: namely, non-verbal behaviour in the doctor-patient interaction. We review 2 lines of research on race and non-verbal behaviour: (i) the ways in which a patient's race can influence a doctor's non-verbal behaviour toward the patient, and (ii) the relative difficulty that doctors can have in accurately understanding the nonverbal communication of non-White patients. Further, we review research on the implications that both lines of work can have for the doctor-patient relationship and the patient's health. The research we review suggests that White doctors interacting with minority group patients are likely to behave and respond in ways that are associated with worse health outcomes. As doctors' disengaged non-verbal behaviour towards minority group patients and lower ability to read minority group patients' non-verbal behaviours may contribute to racial disparities in patients' satisfaction and health outcomes, solutions that target non-verbal behaviour may be effective. A number of strategies for such targeting are discussed. © 2013 John Wiley & Sons Ltd.

  6. Near Earth Objects and Cascading Effects from the Policy Perspective: Implications from Problem and Solution Definition

    NASA Astrophysics Data System (ADS)

    Lindquist, Eric

    2016-04-01

    The characterization of near-Earth-objects (NEOs) in regard to physical attributes and potential risk and impact factors presents a complex and complicates scientific and engineering challenge. The societal and policy risks and impacts are no less complex, yet are rarely considered in the same context as material properties or related factors. Further, NEO impacts are typically considered as discrete events, not as initial events in a dynamic cascading system. The objective of this contribution is to position the characterization of NEOs within the public policy process domain as a means to reflect on the science-policy nexus in regard to risks and multi-hazard impacts associated with these hazards. This will be accomplished through, first, a brief overview of the science-policy nexus, followed by a discussion of policy process frameworks, such as agenda setting and the multiple streams model, focusing events, and punctuated equilibrium, and their application and appropriateness to the problem of NEOs. How, too, for example, does NEO hazard and risk compare with other low probability, high risk, hazards in regard to public policy? Finally, we will reflect on the implications of alternative NEO "solutions" and the characterization of the NEO "problem," and the political and public acceptance of policy alternatives as a way to link NEO science and policy in the context of the overall NH9.12 panel.

  7. Characterization of NEOs from the Policy Perspective: Implications from Problem and Solution Definitions

    NASA Astrophysics Data System (ADS)

    Lindquist, E.

    2015-12-01

    The characterization of near-Earth-objects (NEOs) in regard to physical attributes and potential risk and impact factors presents a complex and complicates scientific and engineering challenge. The societal and policy risks and impacts are no less complex, yet are rarely considered in the same context as material properties or related factors. The objective of this contribution is to position the characterization of NEOs within the public policy process domain as a means to reflect on the science-policy nexus in regard to risks associated with NEOs. This will be accomplished through, first, a brief overview of the science-policy nexus, followed by a discussion of several policy process frameworks, such as agenda setting and the multiple streams model, focusing events, and punctuated equilibrium, and their application and appropriateness to the problem of NEOs. How, too, for example, does NEO hazard and risk compare with other low probability, high risk, hazards in regard to public policy? Finally, we will reflect on the implications of alternative NEO "solutions" and the characterization of the NEO "problem," and the political and public acceptance of policy alternatives as a way to link NEO science and policy in the context of the overall NH004 panel.

  8. Rabbit serum albumin hydrolyzes the carbamate carbaryl.

    PubMed

    Sogorb, Miguel A; Carrera, Victoria; Benabent, Mónica; Vilanova, Eugenio

    2002-04-01

    One of the main detoxification processes of the carbamate insecticides is the hydrolysis of the carbamic ester bond. Carboxylesterases seem to play important roles in the metabolization of carbamates. This study performs a biochemical characterization of the capabilities of rabbit serum albumin (RSA) to hydrolyze the carbamate carbaryl. Rabbit serum albumin was able to hydrolyze carbaryl with a K(cat) of 7.1 x 10(-5) s(-1). The K(m) for this hydrolysis reaction was 240 microM. Human, chicken, and bovine serum albumins were also able to hydrolyze carbaryl. The divalent cation Cu(2+) at 1 mM concentration inhibited around 50% of the hydrolysis of carbaryl by RSA. Other mono- and divalent cations at 1 mM concentration and 5 mM EDTA exerted no significant effects on the hydrolysis of carbaryl by RSA. The inhibition of the carbaryl hydrolysis by sulfydril blocking agents suggests that a cysteine residue plays an important role in the active center of the catalytic activity. Both caprylic and palmitic acids were noncompetitive inhibitors of the carbaryl hydrolysis by RSA. The carboxyl ester p-nitrophenyl butyrate is a substrate of RSA and competitively inhibited the hydrolysis of carbaryl by this protein, suggesting that the hydrolysis of carbaryl and the hydrolysis of carboxyl esters occur in the same catalytic site and through a similar mechanism. This mechanism might be based on the carbamylation of a tyrosine residue of the RSA. Serum albumin is a protein universally present in nontarget species of insecticides; therefore, the capability of this protein to hydrolyze other carbamates must be studied because it might have important toxicological and ecotoxicological implications.

  9. Thiophilic interaction chromatography of serum albumins.

    PubMed

    Bourhim, Mustapha; Rajendran, Anita; Ramos, Yanira; Srikrishnan, Thamarapu; Sulkowski, Eugene

    2008-07-01

    An investigation of the binding of native and recombinant human serum albumin and bovine serum albumin on three thiophilic gels, PyS, 2S, and 3S was performed. In addition to these proteins, we studied serum albumins from several species such as goat, rabbit, guinea pig, rat, hamster, baboon, and pig. Our results reveal that recombinant human serum albumin (rHSA) binds completely to PyS whereas native human serum albumin and bovine serum albumin bind only partially to PyS. The binding affinities of rHSA, human serum albumin and bovine serum albumin to 2S and 3S gels are less than their binding to PyS. Serum albumins from goat, rabbit, guinea pig, rat, hamster, baboon, and pig bind much stronger to 3S gel than human and bovine serum albumins. The binding of pig and hamster serum albumins is stronger than that of rat, goat, baboon, and rabbit.

  10. Results of a survey on albumin use in clinical practice in intensive care units.

    PubMed

    Estébanez-Montiel, M B; Quintana-Díaz, M; García de Lorenzo y Mateos, A; Blancas Gomez-Casero, R; Acosta-Escribano, J; Marcos-Neira, P

    2014-10-01

    Human albumin solutions are used in a number of disorders, though their indications are not clear in all circumstances. These solutions are costly, and their benefit has not been established in all settings. It is therefore interesting to assess the presence of albumin solutions in the daily clinical practice of critical care professionals. To report the standard clinical practices and to describe the variability of albumin solutions use in critically ill patients. A survey sent by e-mail to Spanish and South American Intensive Care Units (ICUs) Planning and execution during the year 2012. A questionnaire comprising 35 questions. Fifty-seven surveys were analyzed. The use of albumin solutions was sporadic or negligible in critically ill patients (96.5%). The exceptions were patients with liver disease (87.7% of the responders administered albumin to these patients). A high percentage of professionals claimed to know the available scientific evidence on the use of albumin in patients with liver disease (82.5%) and in patients without liver disease (77.2%). Only 5.3% of the responders preferred to rely on their own experience to establish the indications of albumin use. The use of albumin solutions is infrequent in ICUs, except in patients with liver disease. Evidence-based knowledge on albumin use is declared to be extensive in ICUs. As a rule, opinions on the use of albumin solutions are based on the scientific recommendations, especially in patients with liver disease. Professional experience rarely prevails over the published clinical guidelines. Copyright © 2013 Elsevier España, S.L.U. and SEMICYUC. All rights reserved.

  11. Albumin reverses the echinocytic shape transformation of stored erythrocytes.

    PubMed

    Reinhart, Sophie A; Schulzki, Thomas; Reinhart, Walter H

    2015-01-01

    The storage of red blood cells (RBCs) leads to storage lesions, which have a negative impact on the clinical outcome after transfusion. A hallmark of storage lesions is echinocytosis. Albumin may reverse this shape transformation, which was the topic of this study. Echinocytosis was generated by incubation of blood for 48 h at room temperature or in RBC units stored 48 days at 5°C. Human serum albumin was diluted in phosphate-buffered saline. RBCs were fixed in 1% glutaraldehyde and examined by light and scanning electron microscopy. The degree of echinocytosis was quantified by calculating the morphological index. Incubation and storage of RBCs led to an echinocytic shape transformation, which was reversible upon incubation in albumin solutions. This process was time-, concentration- and hematocrit-dependent. Treating RBC units at the end of their shelf-life by adding 20% albumin or washing them in 0.2% albumin reversed all degrees of echinocytosis towards discocytosis. In conclusion, albumin has the capacity to reverse echinocytosis generated by RBC storage. This observation may improve the quality of RBC units stored for longer periods of time.

  12. Mineralisation of two phosphate ceramics in HBSS: role of albumin.

    PubMed

    Marques, P A A P; Serro, A P; Saramago, B J; Fernandes, A C; Magalhães, M C F; Correia, R N

    2003-02-01

    The role of albumin in the mineralisation process of commercial hydroxyapatite (HAp) and synthesised biphasic (HAp-tricalcium phosphate) ceramics in a bufferless simulated inorganic plasma (HBSS) was investigated by conventional in vitro tests and static and dynamic wettability measurements. Albumin was either pre-adsorbed or solubilised in HBSS. It was found that calcium complexation by albumin plays a key role in early mineralisation kinetics, so that mineralisation is favoured when albumin is pre-adsorbed and hindered when it is dissolved in HBSS. In the biphasic ceramic this picture is complicated by the fact that albumin, in solution, seems to promote the dissolution of tricalcium phosphate, and simultaneously compete for calcium with the ceramic. It also appears that albumin has a stabilising effect of octacalcium phosphate present in deposits on commercial HAp. The same effect may be present in the case of the biphasic ceramic, at earlier mineralisation times, when octacalcium phosphate appears as a precursor of HAp. Octacalcium phosphate formation on commercial apatite is accompanied by carbonate substitution in phosphate positions.

  13. Albumin administration in the acutely ill: what is new and where next?

    PubMed Central

    2014-01-01

    Albumin solutions have been used worldwide for the treatment of critically ill patients since they became commercially available in the 1940s. However, their use has become the subject of criticism and debate in more recent years. Importantly, all fluid solutions have potential benefits and drawbacks. Large multicenter randomized studies have provided valuable data regarding the safety of albumin solutions, and have begun to clarify which groups of patients are most likely to benefit from their use. However, many questions remain related to where exactly albumin fits within our fluid choices. Here, we briefly summarize some of the physiology and history of albumin use in intensive care before offering some evidence-based guidance for albumin use in critically ill patients. PMID:25042164

  14. Albumin administration in the acutely ill: what is new and where next?

    PubMed

    Vincent, Jean-Louis; Russell, James A; Jacob, Matthias; Martin, Greg; Guidet, Bertrand; Wernerman, Jan; Ferrer, Ricard; Roca, Ricard Ferrer; McCluskey, Stuart A; Gattinoni, Luciano

    2014-07-16

    Albumin solutions have been used worldwide for the treatment of critically ill patients since they became commercially available in the 1940s. However, their use has become the subject of criticism and debate in more recent years. Importantly, all fluid solutions have potential benefits and drawbacks. Large multicenter randomized studies have provided valuable data regarding the safety of albumin solutions, and have begun to clarify which groups of patients are most likely to benefit from their use. However, many questions remain related to where exactly albumin fits within our fluid choices. Here, we briefly summarize some of the physiology and history of albumin use in intensive care before offering some evidence-based guidance for albumin use in critically ill patients.

  15. Cellular specificity of the blood-CSF barrier for albumin transfer across the choroid plexus epithelium.

    PubMed

    Liddelow, Shane A; Dzięgielewska, Katarzyna M; Møllgård, Kjeld; Whish, Sophie C; Noor, Natassya M; Wheaton, Benjamin J; Gehwolf, Renate; Wagner, Andrea; Traweger, Andreas; Bauer, Hannelore; Bauer, Hans-Christian; Saunders, Norman R

    2014-01-01

    To maintain the precise internal milieu of the mammalian central nervous system, well-controlled transfer of molecules from periphery into brain is required. Recently the soluble and cell-surface albumin-binding glycoprotein SPARC (secreted protein acidic and rich in cysteine) has been implicated in albumin transport into developing brain, however the exact mechanism remains unknown. We postulate that SPARC is a docking site for albumin, mediating its uptake and transfer by choroid plexus epithelial cells from blood into cerebrospinal fluid (CSF). We used in vivo physiological measurements of transfer of endogenous (mouse) and exogenous (human) albumins, in situ Proximity Ligation Assay (in situ PLA), and qRT-PCR experiments to examine the cellular mechanism mediating protein transfer across the blood-CSF interface. We report that at all developmental stages mouse albumin and SPARC gave positive signals with in situ PLAs in plasma, CSF and within individual plexus cells suggesting a possible molecular interaction. In contrast, in situ PLA experiments in brain sections from mice injected with human albumin showed positive signals for human albumin in the vascular compartment that were only rarely identifiable within choroid plexus cells and only at older ages. Concentrations of both endogenous mouse albumin and exogenous (intraperitoneally injected) human albumin were estimated in plasma and CSF and expressed as CSF/plasma concentration ratios. Human albumin was not transferred through the mouse blood-CSF barrier to the same extent as endogenous mouse albumin, confirming results from in situ PLA. During postnatal development Sparc gene expression was higher in early postnatal ages than in the adult and changed in response to altered levels of albumin in blood plasma in a differential and developmentally regulated manner. Here we propose a possible cellular route and mechanism by which albumin is transferred from blood into CSF across a sub-population of specialised

  16. VOLUME RESUSCITATION FROM HEMORRHAGIC SHOCK WITH ALBUMIN AND HEXA PEGYLATED HUMAN SERUM ALBUMIN

    PubMed Central

    Cabrales, Pedro; Tsai, Amy G.; Ananda, K.; Acharya, Seetharama A.; Intaglietta, Marcos

    2009-01-01

    The effect of restoring intravascular volume with polyethylene glycol (PEG) conjugated to human serum albumin (PEG-Alb) on systemic parameters and microvascular hemodynamics after hemorrhagic shock resuscitation was studied in the hamster window chamber model. Moderate hemorrhagic shock was induced by controlled arterial bleeding of 50% of blood volume, and hypovolemia was maintained for 1 hour. Fluid resuscitation was accomplished by infusion of 25% of blood volume and recovery was followed over 90 minutes. The PEG-Alb (six chains of maleimide phenyl PEG conjugated human serum albumin at 4%) resuscitation group was compared human serum albumin (HSA) at 5% (HSA5) and 10% (HSA10) protein concentrations. Systemic parameters, microvascular perfusion and capillary perfusion (functional capillary density, FCD) were measured by noninvasive methods. Hyperoncotic solutions provided rapid restoration of blood pressure, blood gas parameters and microvascular perfusion. Systemic and microvascular recovery was best and most rapid with PEG-Alb and followed by HSA10 and HSA5 rapid. Only recovery with PEG-Alb was sustained beyond 90 min. Hemodynamic functional benefits of PEG-Alb and the potential disadvantages associated with HSA, suggest PEG-Alb as better resuscitation solution. PMID:18621463

  17. Human albumin: old, new, and emerging applications.

    PubMed

    Rozga, Jacek; Piątek, Tomasz; Małkowski, Piotr

    2013-05-10

    Human serum albumin has been widely used in an array of clinical settings for nearly 7 decades. Although there is no evidence to support the use of albumin rather than crystalloid in acute volume resuscitation, many clinicians continue to use albumin because it has other important physiologic effects besides the oncotic function. In keeping with the improved understanding of albumin physiology and pathophysiology of many acute and chronic diseases, use of albumin for medical applications has increased in recent years. This, along with increased costs of manufacturing and lower production volume of medical-grade albumin, has lead to an ongoing shortage and rapid increase in albumin prices. This review is based on the analysis of major publications, related to albumin chemistry, physiology, and medical uses including guidelines developed by professional and governmental organizations. Results reflect current knowledge about the role of albumin in health and disease and relevance of albumin therapy in specific clinical settings. Albumin therapy is currently recommended in spontaneous bacterial peritonitis with ascites, refractory ascites not responsive to diuretics, large-volume paracentesis, post-paracentesis syndrome, and the treatment of hepatorenal syndrome as an adjunct to vasoconstrictors. New indications for albumin therapy are linked to the antioxidant activity of albumin and its effects on capillary integrity. In recent years, large-pore hemofiltration and albumin exchange have emerged as promising liver support therapies for liver failure and other toxic syndromes. They are designed to remove a broad range of blood-borne toxins and to restore normal functions of the circulating albumin by replacing defective forms of albumin and albumin molecules saturated with toxins with normal albumin. In view of the ongoing worldwide shortage and high cost of human albumin (native and recombinant), new usage criteria, protocols, and guidelines for appropriate utilization

  18. Pharmaceutical-grade albumin: impaired drug-binding capacity in vitro

    PubMed Central

    Olsen, Harald; Andersen, Anders; Nordbø, Arve; Kongsgaard, Ulf E; Børmer, Ole P

    2004-01-01

    Background Albumin is the most abundant protein in blood plasma, and due to its ligand binding properties, serves as a circulating depot for endogenous and exogenous (e.g. drugs) compounds. Hence, the unbound drug is the pharmacologically active drug. Commercial human albumin preparations are frequently used during surgery and in critically ill patients. Recent studies have indicated that the use of pharmaceutical-grade albumin is controversial in critically ill patients. In this in vitro study we investigated the drug binding properties of pharmaceutical-grade albumins (Baxter/Immuno, Octapharma, and Pharmacia & Upjohn), native human serum, and commercially available human serum albumin from Sigma Chemical Company. Methods The binding properties of the various albumin solutions were tested in vitro by means of ultrafiltration. Naproxen, warfarin, and digitoxin were used as ligands. HPLC was used to quantitate the total and free drug concentrations. The data were fitted to a model of two classes of binding sites for naproxen and warfarin and one class for digitoxin, using Microsoft Excel and Graphpad Prism. Results The drugs were highly bound to albumin (95–99.5%). The highest affinity (lowest K1) was found with naproxen. Pharmaceutical-grade albumin solutions displayed significantly lower drug-binding capacity compared to native human serum and Sigma albumin. Thus, the free fraction was considerably higher, approximately 40 times for naproxen and 5 and 2 times for warfarin and digitoxin, respectively. The stabilisers caprylic acid and N-acetyl-DL-tryptophan used in the manufacturing procedure seem to be of importance. Adding the stabilisers to human serum and Sigma albumin reduced the binding affinity whereas charcoal treatment of the pharmaceutical-grade albumin from Octapharma almost restored the specific binding capacity. Conclusion This in vitro study demonstrates that the specific binding for warfarin and digitoxin is significantly reduced and for naproxen

  19. Evaluation of human and bovine serum albumin on oxidation characteristics by a photosensitization reaction under complete binding of talaporfin sodium.

    PubMed

    Kurotsu, Mariko; Yajima, Masahiro; Takahashi, Mei; Ogawa, Emiyu; Arai, Tsunenori

    2015-09-01

    In order to investigate the therapeutic interaction of an extra-cellular photosensitization reaction, we evaluated the oxidation characteristics of human and bovine serum albumin by this reaction with talaporfin sodium under complete binding with albumin by spectroscopic analysis in a cell-free solution. The solution was composed of 20μg/ml talaporfin sodium and 2.1mg/ml human or bovine serum albumin. A 662nm laser light was used to irradiate the solution. Visible absorbance spectra of solutions were measured to obtain the oxidized and non-oxidized relative densities of albumin and talaporfin sodium before and after the photosensitization reaction. The defined oxidation path ratio of talaporfin sodium to albumin reflected the oxidation of the solution. Absorbance wavelengths at approximately 240 and 660nm were used to calculate normalized molecular densities of oxidized albumin and talaporfin sodium, respectively. The oxidation path ratio of talaporfin sodium to albumin when binding human serum albumin was approximately 1.8 times larger than that of bovine serum albumin during the photosensitization reaction from 1 to 50J/cm(2). We hypothesized that the oxidation path ratio results might have been caused by talaporfin sodium binding affinity or binding location difference between the two albumins, because the fluorescence lifetimes of talaporfin sodium bound to human and bovine serum albumin were 7.0 and 4.9ns, respectively. Therefore, the photodynamic therapeutic interaction might be stronger with human serum albumin than with bovine serum albumin in the case of extracellular photosensitization reaction. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Protection by albumin against ischaemia- and hypoxia-induced hepatic injury.

    PubMed

    Strubelt, O; Younes, M; Li, Y

    1994-11-01

    In previous studies using isolated perfused rat livers, we have shown that reactive oxygen species are involved in hypoxic and ischaemic liver damage. Since albumin was shown to possess strong antioxidant properties we now investigated the capacity of albumin to prevent ischaemic and hypoxic damage in isolated perfused rat livers. Both, partial ischaemia and hypoxia/reoxygenation, resulted in marked hepatic injury as evidenced by an increased release of hepatic enzymes (GPT, LDH), by a strong decline of bile flow and by a decrease in hepatic GSH levels. With partial ischaemia, hepatic ATP depletion and calcium accumulation were also observed. Bovine serum albumin, added to the perfusate at concentrations of 0.1 or 1%, provided nearly complete protection against both types of liver injury. The same level of protection was also afforded by sulfhydryl-blocked and fatty acid-free bovine albumin preparations and by human albumin. In conclusion, the protective effect of albumin in our models of oxidative liver injury is neither due to the thiol moiety nor to the presence of oxidizable fatty acids in the albumin fraction. More likely, albumin provides protection by an unspecific binding of redox-active transition metal ions capable of catalyzing reactions which yield hydroxyl or hydroxyl-like radicals. Besides, unspecific sacrifice reactions of albumin with highly reactive oxygen species or other endogenous compounds may also be implicated.

  1. Does administering albumin to postoperative gastroschisis patients improve outcome?

    PubMed Central

    Tannuri, Ana Cristina A; Silva, Luanna M; Leal, Antonio José G; de Moraes, Augusto César F; Tannuri, Uenis

    2012-01-01

    OBJECTIVES: Newborns who undergo surgery for gastroschisis correction may present with oliguria, anasarca, prolonged postoperative ileus, and infection. New postoperative therapeutic procedures were tested with the objective of improving postoperative outcome. PATIENTS AND METHODS: One hundred thirty-six newborns participated in one of two phases. Newborns in the first phase received infusions of large volumes of crystalloid solution and integral enteral formula, and newborns in the second phase received crystalloid solutions in smaller volumes, with albumin solution infusion when necessary and the late introduction of a semi-elemental diet. The studied variables were serum sodium and albumin levels, the need for albumin solution expansion, the occurrence of anasarca, the length of time on parenteral nutrition, the length of time before initiating an enteral diet and reaching a full enteral diet, orotracheal intubation time, length of hospitalization, and survival rates. RESULTS: Serum sodium levels were higher in newborns in the second phase. There was a correlation between low serum sodium levels and orotracheal intubation time; additionally, low serum albumin levels correlated with the length of time before the initiation of an oral diet and the time until a full enteral diet was reached. However, the discharge weights of newborns in the second phase were higher than in the first phase. The other studied variables, including survival rates (83.4% and 92.0%, respectively), were similar for both phases. CONCLUSIONS: The administration of an albumin solution to newborns in the early postoperative period following gastroschisis repair increased their low serum sodium levels but did not improve the final outcome. The introduction of a semi-elemental diet promoted an increase in body weight at the time of discharge. PMID:22358234

  2. THE REACTIONS OF IODINE AND IODOACETAMIDE WITH NATIVE EGG ALBUMIN

    PubMed Central

    Anson, M. L.

    1940-01-01

    The following experimental results have been obtained. 1. Native egg albumin treated with iodine and then denatured no longer gives a nitroprusside test or reduces dilute ferricyanide in neutral Duponol PC solution. 2. More iodine is needed to abolish the ferricyanide reduction if the reaction between native egg albumin and iodine is carried out at pH 6.8 than if the reaction is carried out at pH 3.2. At pH 6.8 iodine reacts with tyrosine as well as with cysteine. 3. Cysteine and tryptophane are the only amino acids with reducing groups which are known to react with dilute iodine at pH 3.2 The reducing power of cysteine is abolished by the reaction with iodine, whereas the reducing power of tryptophane remains intact. Pepsin and chymotrypsinogen which contain tryptophane but not cysteine, do not react at all with dilute iodine at pH 3.2. 4. Native egg albumin treated with iodoacetamide at pH 9.0 and then denatured by Duponol PC reduces only 60 per cent as much dilute ferricyanide as egg albumin which has not been treated with iodoacetamide. 5. The SH group is the only protein reducing group which is known to react with iodoacetamide. The simplest explanation of the new observation that the SH groups of egg albumin can be modified by reactions with the native form of the protein is that the native egg albumin has free and accessible but relatively unreactive SH groups which can react with iodine and iodoacetamide despite the fact that they do not react with ferricyanide, porphyrindin, or nitroprusside. Preliminary experiments suggested by the results with egg albumin indicate that the tobacco mosaic virus is modified by iodine at pH 2.8 without being inactivated and that the tobacco mosaic and rabbit papilloma viruses are not inactivated by iodoacetamide at pH 8.0. PMID:19873158

  3. Interaction of glucocorticoids and progesterone derivatives with human serum albumin.

    PubMed

    Abboud, Rola; Akil, Mohammad; Charcosset, Catherine; Greige-Gerges, Hélène

    2017-10-01

    Glucocorticoids (GCs) and progesterone derivatives (PGDs) are steroid hormones with well-known biological activities. Their interaction with human serum albumin (HSA) may control their distribution. Their binding to albumin is poorly studied in literature. This paper deals with the interaction of a series of GCs (cortisol, cortisone, prednisolone, prednisone, 6-methylprednisolone and 9-fluorocortisol acetate) and PGDs (progesterone, hydroxylated PGDs, methylated PGDs and dydrogesterone) with HSA solution (pH 7.4) at molar ratios steroid to HSA varying from 0 to 10. Similar titrations were conducted using Trp aqueous solution. Fluorescence titration method and Fourier transform infrared spectroscopy (FTIR) are used. PGDs (except dydrogesterone), cortisone and 9-fluorocortisol acetate affected weakly the fluorescence of Trp in buffer solution while they decreased in a dose-dependent manner that of HSA. Their binding constants to HSA were then calculated. Moreover, displacement experiment was performed using bilirubin as a site marker. The binding constant of bilirubin to albumin was determined in the absence and presence of a steroid at a molar ratio steroid to HSA of 1. The results indicate that the steroids bind to HSA at site I in a pocket different from that of bilirubin. Furthermore, the peak positions of amide I and amide II bands of HSA were shifted in the presence of progesterone, dydrogesterone and GCs. Also a variation was observed in amide I region indicating the formation of hydrogen bonding between albumin and steroids. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Boiling characteristics of dilute polymer solutions and implications for the suppression of vapor explosions

    SciTech Connect

    Bang, K.H.; Kim, M.H.

    1995-09-01

    Quenching experiments of hot solid spheres in dilute aqueous solutions of polyethylene oxide polymer have been conducted for the purpose of investigating the physical mechanisms of the suppression of vapor explosions in this polymer solutions. Two spheres of 22.2mm and 9.5mm-diameter were tested in the polymer solutions of various concentrations at 30{degrees}C. Minimum film boiling temperature ({Delta}T{sub MFB}) in this highly-subcooled liquid rapidly decreased from over 700{degrees}c for pure water to about 150{degrees}C as the polymer concentration was increased up to 300ppm for 22.2mm sphere, and it decreased to 350{degrees}C for 9.5mm sphere. This rapid reduction of minimum film boiling temperature in the PEO aqueous solutions can explain its ability of the suppression of spontaneous vapor explosions. The ability of suppression of vapor explosions by dilute polyethylene oxide solutions against an external trigger pressure was tested by dropping molten tin into the polymer solutions at 25{degrees}C. It was observed that in 50ppm solutions more mass fragmented than in pure water, but produced weaker explosion pressures. The explosion was completely suppressed in 300ppm solutions with the external trigger. The debris size distributions of fine fragments smaller than 0.7mm were shown almost identical regardless of the polymer concentrations.

  5. Solution-Focused Brief Therapy: Overview and Implications for School Counselors

    ERIC Educational Resources Information Center

    Brasher, Kitty L.

    2009-01-01

    Solution-focused brief therapy is a fairly new approach of counseling that has been found to be useful in various settings. The strategy's usefulness and limitations in a school setting will be examined in this article. Included in the article are the basic components of the solution-focused approach, questions significant to the strategy,…

  6. Amadori albumin in diabetic nephropathy

    PubMed Central

    Neelofar, Km.; Ahmad, Jamal

    2015-01-01

    Nonenzymatic glycation of macromolecules in diabetes mellitus (DM) is accelerated due to persistent hyperglycemia. Reducing sugar such as glucose reacts non enzymatically with free €-amino groups of proteins through series of reactions forming Schiff bases. These bases are converted into Amadori product and further into AGEs. Non enzymatic glycation has the potential to alter the biological, structural and functional properties of macromolecules both in vitro and in vivo. Studies have suggested that amadori as well as AGEs are involved in the micro-macro vascular complications in DM, but most studies have focused on the role of AGEs in vascular complications of diabetes. Recently putative AGE-induced patho-physiology has shifted attention from the possible role of amadori-modified proteins, the predominant form of the glycated proteins in the development of the diabetic complications. Human serum albumin (HSA), the most abundant protein in circulation contains 59 lysine and 23 arginine residues that could, in theory be involved in glycation. Albumin has dual nature, first as a marker of intermediate glycation and second as a causative agent of the damage of tissues. Among the blood proteins, hemoglobin and albumin are the most common proteins that are glycated. HSA with a shorter half life than RBC, appears to be an alternative marker of glycemic control as it can indicate blood glucose status over a short period (2-3 weeks) and being unaffected by RBCs life span and variant haemoglobin, anemia etc which however, affect HbA1c. On the other hand, Amadori albumin may accumulate in the body tissues of the diabetic patients and participate in secondary complications. Amadori-albumin has potential role in diabetic glomerulosclerosis due to long term hyperglycaemia and plays an important role in the pathogenesis of diabetic nephropathy. This review is an approach to compile both the nature of glycated albumin as a damaging agent of tissues and as an intermediate

  7. PRODUCTION OF UNIFORMLY SIZED SERUM ALBUMIN AND DEXTROSE MICROBUBBLES

    PubMed Central

    Borrelli, Michael J.; O’Brien, William D.; Bernock, Laura J.; Williams, Heather R.; Hamilton, Eric; Wu, Jonah; Oelze, Michael L.; Culp, William C.

    2011-01-01

    Uniformly-sized preparations with average microbubble (MB) diameters from 1 µm to 7 µm were produced reliably by sonicating decafluorobutane-saturated solutions of serum albumin and dextrose. Detailed protocols for producing and size-separating the MBs are presented, along with the effects that changing each production parameter (serum albumin concentration, sonication power, sonication time, etc.) had on MB size distribution and acoustic stability. These protocols can be used to produce MBs for experimental applications or serve as templates for developing new protocols that yield MBs with physical and acoustic properties better suited to specific applications. Size stability and ultrasonic performance quality control tests were developed to assure that successive MB preparations perform identically and to distinguish the physical and acoustic properties of identically sized MBs produced with different serum albumin-dextrose formulations and sonication parameters. MBs can be stored at 5°C for protracted periods (2 weeks to one year depending on formulation). PMID:21689961

  8. Dielectric behavior and atomic structure of serum albumin.

    PubMed

    Oncley, J L

    2003-01-01

    After 1946, serum albumin was available for studies. Its residue sequence and internal disulfide bonding was developed by 1976. We began to make dielectric dispersion studies and apply Perrin's equations for rotational relaxation times around the two axes of revolution in 1938. These data indicated that albumin should have an elongated shape. In 1992 atomic structure data indicated the molecule was heart-shaped. A similar 1998 study of albumin complexed with fatty acid showed that the molecule was substantially rearranged. We found that the dielectric constant of albumin solutions was sensitive to fatty acid content, making this property an attractive probe in stop-flow kinetic studies. Such studies show that the fatty acid reaction is a two-step process. The fatty acid first binds to exterior sites in a diffusion-limited second order reaction complete in 1 ms. Then a first order rearrangement reaction with approximately 400 ms half-life follows. Thus the highly specialized serum albumin sequence of amino acid residues determines not only the structure of the unligated molecule, but also the distinctive structures of the numerous multiligated molecules.

  9. Industrial stabilizers caprylate and N-acetyltryptophanate reduce the efficacy of albumin in liver patients.

    PubMed

    Stange, Jan; Stiffel, Melanie; Goetze, Anne; Strube, Sabrina; Gruenert, Juliane; Klammt, Sebastian; Mitzner, Steffen; Koball, Sebastian; Liebe, Stefan; Reisinger, Emil

    2011-06-01

    Liver failure is associated with an accumulation of toxic molecules that exert an affinity to albumin. Some of them have vasoactive activity. So far, albumin has been used as a plasma expander to improve the available circulating blood volume. However, recent studies have suggested that albumin is more effective than starch for this indication. It has not been reported yet whether the industrial stabilizers octanoate and N-acetyltryptophanate, added to albumin, occupy binding sites for vasoactive substances. The aim of this study was to determine whether the presence of the industrial stabilizers octanoate and caprylate has an impact on the effect of the albumin-binding function or circulating blood volume in patients with cirrhosis, portal hypertension, and an indication for albumin. In 25 patients who received albumin via an inline infusion filter that depleted stabilizers, there was an improvement of albumin binding, and there was less deterioration of circulating blood volume and renal function in comparison with a control group. Further studies are needed to confirm the results and identify the potential socioeconomic side effects of industrial stabilizers in commercial albumin solutions.

  10. Solution-mediated phase transformation: significance during dissolution and implications for bioavailability.

    PubMed

    Greco, Kristyn; Bogner, Robin

    2012-09-01

    Solubility improvement of poorly soluble drug compounds is a key approach to ensuring the successful development of many new drugs. Methods used to improve the solubility of drug compounds include forming a salt, cocrystal, or amorphous solid. These methods of improving solubility can often lead to a phenomenon called solution-mediated phase transformation, a phase change that is facilitated through exposure to solution. Solution-mediated phase transformation occurs in three steps: dissolution to create a supersaturated solution followed by nucleation of less soluble phase and the growth of that phase. When the growth of the less soluble phase occurs on the surface of the metastable solid, this phenomenon can cause a marked decrease in dissolution rate during in vitro dissolution evaluation, and ultimately in vivo. Therefore, transformation to a less soluble solid during dissolution is an important aspect to consider when evaluating approaches to increase the solubility of a poorly soluble drug. Identification of solution-mediated phase transformation during dissolution is reviewed for powder dissolution, rotating disk method, and channel flow-through apparatus. Types of solution-mediated phase transformation are described in this report, including those involving salts, polymorphs, amorphous solids, and cocrystals. Many experimental examples are provided. Evidence of potential solution-mediated phase transformation in vivo is discussed to better understand the relationship between in vitro dissolution evaluation and in vivo performance.

  11. Perceptions of injury causes and solutions in a Johannesburg township: implications for prevention.

    PubMed

    Butchart, A; Kruger, J; Lekoba, R

    2000-02-01

    As with other diseases, citizen perceptions of injury causes and solutions are important determinants of their response to the problem. This study explores qualitative responses to questions about the causes and solutions for injuries due to violence, transport, and unintentional burns, falls and other causes from 1,075 residents in six neighbourhoods of a low-income area in Johannesburg, South Africa. These included council houses, council apartment blocks and informal settlements. Data were analysed using content analytic procedures. Perceived causes of injury varied sharply between neighbourhoods. Violence was seen as an outcome of unemployment, socialisation, drug abuse and drug dealing in the formal housing areas, while in the informal settlements it was attributed to unemployment, poor housing and environmental conditions, and excessive alcohol consumption. In the formal housing areas, suggested solutions for violence emphasised increased policing and other repressive measures that contradicted the attribution of causes to environmental factors. In the informal areas, solutions were more congruent with perceived causes, emphasising housing development, education and employment. Perceived causes and solutions for transport injuries reflected the specific context of each neighbourhood, and indicated strong support for the implementation of environmental modifications to reduce the speed of motor vehicles and thus the number of pedestrian injuries. Where perceived causes and solutions for violence and transport-related injuries were located beyond the community in the broader environment, unintentional injuries due to other causes were seen as more in the sphere of potential personal control, except in the informal areas where electrification and formal housing provision were the most commonly suggested solutions. Popular constructions of the causes and solutions for major categories of injury are important in shaping injury prevention responses, and their

  12. Automated calibration of a stream solute transport model: Implications for interpretation of biogeochemical parameters

    USGS Publications Warehouse

    Scott, D.T.; Gooseff, M.N.; Bencala, K.E.; Runkel, R.L.

    2003-01-01

    The hydrologic processes of advection, dispersion, and transient storage are the primary physical mechanisms affecting solute transport in streams. The estimation of parameters for a conservative solute transport model is an essential step to characterize transient storage and other physical features that cannot be directly measured, and often is a preliminary step in the study of reactive solutes. Our study used inverse modeling to estimate parameters of the transient storage model OTIS (One dimensional Transport with Inflow and Storage). Observations from a tracer injection experiment performed on Uvas Creek, California, USA, are used to illustrate the application of automated solute transport model calibration to conservative and nonconservative stream solute transport. A computer code for universal inverse modeling (UCODE) is used for the calibrations. Results of this procedure are compared with a previous study that used a trial-and-error parameter estimation approach. The results demonstrated 1) importance of the proper estimation of discharge and lateral inflow within the stream system; 2) that although the fit of the observations is not much better when transient storage is invoked, a more randomly distributed set of residuals resulted (suggesting non-systematic error), indicating that transient storage is occurring; 3) that inclusion of transient storage for a reactive solute (Sr2+) provided a better fit to the observations, highlighting the importance of robust model parameterization; and 4) that applying an automated calibration inverse modeling estimation approach resulted in a comprehensive understanding of the model results and the limitation of input data.

  13. Isotope fractionation in phase-transfer processes under thermodynamic and kinetic control - Implications for diffusive fractionation in aqueous solution.

    PubMed

    Kopinke, Frank-Dieter; Georgi, Anett; Roland, Ulf

    2017-08-15

    Diffusive isotope fractionation of organic compounds in aqueous solution was investigated by means of liquid-liquid and liquid-gas partitioning experiments under kinetic control. The two-film model was used to describe phase-transfer kinetics. It assumes the diffusion of solutes across a stagnant water boundary layer as the rate-controlling step. For all investigated solutes (benzene-D0 and -D6, toluene-D0, -D5, and -D8, cyclohexane-D0 and -D12), there was no significant observable fractionation effect between nondeuterated and perdeuterated isotopologues, resulting in a ratio of diffusion coefficients Dlight: Dheavy=1.00±0.01. In addition, isotope fractionation due to equilibrium partitioning of solutes between water and n-octane or gas phase was measured. The deuterated compounds are more hydrophilic than their light isotopologues in all cases, giving rise to fractionation coefficients αHpart=Koctane/water,H: Koctane/water,D=1.085 to 1.15. Thus, thermodynamic fractionation effects are much larger than diffusion fractionation effects. Methodical and environmental implications of these findings are discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Correctional officers' perceptions of a solution-focused training program: potential implications for working with offenders.

    PubMed

    Pan, Peter Jen Der; Deng, Liang-Yu F; Chang, Shona Shih Hua; Jiang, Karen Jye-Ru

    2011-09-01

    The purpose of this exploratory study was to explore correctional officers' perceptions and experiences during a solution-focused training program and to initiate development of a modified pattern for correctional officers to use in jails. The study uses grounded theory procedures combined with a follow-up survey. The findings identified six emergent themes: obstacles to doing counseling work in prisons, offenders' amenability to change, correctional officers' self-image, advantages of a solution-focused approach (SFA), potential advantages of applying SFA to offenders, and the need for the consolidation of learning and transformation. Participants perceived the use of solution-focused techniques as appropriate, important, functional, and of only moderate difficulty in interacting with offenders. Finally, a modified pattern was developed for officers to use when working with offenders in jails. Suggestions and recommendations are made for correctional interventions and future studies.

  15. On the statistical solution of the Riemann equation and its implications for Burgers turbulence

    SciTech Connect

    E, W.; Vanden Eijnden, E.

    1999-08-01

    The statistics of the multivalued solutions of the forced Riemann equation, u{sub t}+uu{sub x}=f, is considered. An exact equation for the signed probability density function of these solutions and their gradient {xi}=u{sub x} is derived, and some properties of this equation are analyzed. It is shown in particular that the tails of the signed probability density function generally decay as {vert_bar}{xi}{vert_bar}{sup {minus}3} for large {vert_bar}{xi}{vert_bar}. Further considerations give bounds on the cumulative probability density function for the velocity gradient of the solution of Burgers equation. {copyright} {ital 1999 American Institute of Physics.}

  16. Amorphous material from the rapid evaporation of basalt weathering solutions: Implications for Amazonian alteration

    NASA Astrophysics Data System (ADS)

    Smith, R.; Horgan, B. H. N.; Christensen, P. R.

    2016-12-01

    Amorphous silicates of ambiguous origin are detected on the Martian surface through orbiter and rover measurements. Secondary amorphous silicates might precipitate from rapidly evaporating weathering solutions under Amazonian ( 3 BYA - present) surface conditions. Yet, such phases are poorly understood and are underrepresented in infrared spectral libraries. Amazonian weathering was simulated by dissolving two basaltic tephra compositions in DI water under two different atmospheres (1: oxidizing and 2: simulated Martian). The resulting weathering solutions were rapidly evaporated into sample cups. Precipitate mineralogy was studied using visible and near-infrared (VNIR) and thermal-infrared (TIR) spectroscopy and x-ray diffraction (XRD). Solution compositions were analyzed using Ion Chromatography (IC) and Inductively Coupled Plasma Mass-Spectroscopy (ICP-MS). All experiments formed hydrated amorphous silicates and nanophase iron-oxides, but precipitates from solutions formed under a simulated Martian atmosphere also contain crystalline carbonate and sulfate minerals. The oxidizing atmosphere precipitates are also S-bearing, based on solution chemistry, but no crystalline sulfates were unambiguously detected. The TIR spectra of all samples exhibit a spectral feature at 460 cm-1 that was previously only known to be present in the spectra of basaltic glass and some terrestrial palagonitized basalt samples, indicating that the precipitates are new to spectral libraries. Ongoing characterization will help determine the composition and structure of the amorphous phases. TIR spectral and XRD instruments on the Spirit and Mars Science Laboratory (MSL) rovers both indicate high abundances of basaltic glass in rock and soil samples, despite chemical evidence for aqueous alteration. Our results suggest that these measurements are consistent with secondary amorphous silicates formed through the rapid evaporation of basalt weathering solutions. Thus, transient water

  17. Ligation activity of fragmented ribozymes in frozen solution: implications for the RNA world

    PubMed Central

    Vlassov, Alexander V.; Johnston, Brian H.; Landweber, Laura F.; Kazakov, Sergei A.

    2004-01-01

    A vexing difficulty of the RNA world hypothesis is how RNA molecules of significant complexity could ever have evolved given their susceptibility to degradation. One way degradation might have been reduced is through low temperature. Here we report that truncated and fragmented derivatives of the hairpin ribozyme can catalyze ligation of a wide variety of RNA molecules to a given sequence in frozen solution despite having little or no activity under standard solution conditions. These results suggest that complex RNAs could have evolved in freezing environments on the early earth and perhaps elsewhere. PMID:15161960

  18. Comparative efficiency of final endodontic cleansing procedures in removing a radioactive albumin from root canal systems

    SciTech Connect

    Cecic, P.A.; Peters, D.D.; Grower, M.F.

    1984-09-01

    Fifty-six teeth were initially instrumented, with the use of seven irrigants or irrigant combinations, and filled with radioactive albumin. The study then showed the relative ability of three final endodontic procedures (copious reirrigation with saline solution, drying with paper points, and reassuring patency of the canal with the final instrument) to remove the albumin. Even after copious irrigation, each additional procedure removed statistically significant amounts of albumin. Alternating an organic solvent and an inorganic solvent did appear to leave the canal system in the optimal condition for final cleansing procedures. The study then correlated the relative efficiency of irrigation alone versus instrumentation plus irrigation in removing the remaining albumin from the canal systems. Reinstrumentation plus copious irrigation removed significantly more albumin than copious irrigation alone.

  19. PROPERTY CHANGES IN AQUEOUS SOLUTIONS DUE TO SURFACTANT TREATMENT OF PCE: IMPLICATIONS TO GEOPHYSICAL MEASUREMENTS

    EPA Science Inventory

    Select physicochemical properties of aqueous solutions composed of surfactants, dye, and

    perchloroethylene (PCE) were evaluated through a response surface quadratic design

    model of experiment. Nine surfactants, which are conventionally used in the

    remediation...

  20. PROPERTY CHANGES IN AQUEOUS SOLUTIONS DUE TO SURFACTANT TREATMENT OF PCE: IMPLICATIONS TO GEOPHYSICAL MEASUREMENTS

    EPA Science Inventory

    Select physicochemical properties of aqueous solutions composed of surfactants, dye, and

    perchloroethylene (PCE) were evaluated through a response surface quadratic design

    model of experiment. Nine surfactants, which are conventionally used in the

    remediation...

  1. Intrinsic Bacterial Contamination of a Commercial Iodophor Solution: Investigation of the Implicated Manufacturing Plant

    PubMed Central

    Berkelman, Ruth L.; Anderson, Roger L.; Davis, Barry J.; Highsmith, Anita K.; Petersen, Norman J.; Bond, Walter W.; Cook, E. H.; Mackel, Donald C.; Favero, Martin S.; Martone, William J.

    1984-01-01

    After an outbreak of peritoneal infections attributed to intrinsic contamination of a poloxamer-iodine solution with Pseudomonas aeruginosa, the manufacturer of the contaminated solution permitted investigation and sampling of materials within the plant. Pseudomonas spp. were recovered from two different unopened lots of solution and from numerous water samples obtained at the plant. The isolates from water identical to those of an isolate recovered from Prepodyne solution (West-Agro Chemical Co., Inc., Westwood, Kans., manufactured for AMSCO Medical Products Div., Erie, Pa.) manufactured 1 month earlier at the same plant. P. aeruginosa was not recovered from incoming city water. P. aeruginosa was recovered from sterile water and poloxamer-iodine after 48 h of incubation in a plant polyvinyl chloride pipe. Scanning electron micrographs of polyvinyl chloride pipe used in the plant showed massive concentrations of rod-shaped and coccobacillary cells apparently embedded in interior deposits of the pipe. Manufacturers of iodophors should be aware that pipes or other surfaces colonized with bacteria may be a source of contamination of their products. Images PMID:16346513

  2. Reentrant condensation of lysozyme: Implications for studying dynamics of lysozyme in aqueous solutions of lithium chloride

    SciTech Connect

    Mamontov, Eugene; O'Neill, Hugh Michael

    2014-01-01

    Recent studies have outlined the use of eutectic solution of lithium chloride in water to study microscopic dynamics of lysozyme in an aqueous solvent that is remarkably similar to pure water in many respects, yet allows experiments over a wide temperature range without the solvent crystallization. The eutectic point in (H2O)R(LiCl) system corresponds to R 7.3, and it is of interest to investigate whether less concentrated aqueous solutions of LiCl could be employed in low-temperature studies of a solvated protein. We have investigated a range of concentrations of lysozyme and LiCl in aqueous solutions to identify systems that do not show phase separation and avoid solvent crystallization on cooling down. Compared to the lysozyme concentration in solution, the concentration of LiCl in the aqueous solvent plays the major role in determining systems suitable for low-temperature studies. We have observed interesting and rich phase behavior reminiscent of reentrant condensation of proteins.

  3. Albumin-deficient mouse models for studying metabolism of human albumin and pharmacokinetics of albumin-based drugs

    PubMed Central

    Roopenian, Derry C; Low, Benjamin E; Christianson, Gregory J; Proetzel, Gabriele; Sproule, Thomas J; Wiles, Michael V

    2015-01-01

    Serum albumin is the major determinant of blood colloidal osmotic pressure acting as a depot and distributor of compounds including drugs. In humans, serum albumin exhibits an unusually long half-life mainly due to protection from catabolism by neonatal Fc receptor (FcRn)-mediated recycling. These properties make albumin an attractive courier of therapeutically-active compounds. However, pharmaceutical research and development of albumin-based therapeutics has been hampered by the lack of appropriate preclinical animal models. To overcome this, we developed and describe the first mouse with a genetic deficiency in albumin and its incorporation into an existing humanized FcRn mouse model, B6.Cg-Fcgrttm1Dcr Tg(FCGRT)32Dcr/DcrJ (Tg32). Albumin-deficient strains (Alb-/-) were created by TALEN-mediated disruption of the albumin (Alb) gene directly in fertilized oocytes derived from Tg32 mice and its non-transgenic background control, C57BL/6J (B6). The resulting Alb-/- strains are analbuminemic but healthy. Intravenous administration of human albumin to Tg32-Alb-/- mFcRn-/- hFcRnTg/Tg) mice results in a remarkably extended human albumin serum half-life of ∼24 days, comparable to that found in humans, and in contrast to half-lives of 2.6–5.8 d observed in B6, B6-Alb-/- and Tg32 strains. This striking increase can be explained by the absence of competing endogenous mouse albumin and the presence of an active human FcRn. These novel albumin-deficient models provide unique tools for investigating the biology and pathobiology of serum albumin and are a more appropriate rodent surrogates for evaluating human serum albumin pharmacokinetics and albumin-based compounds. PMID:25654695

  4. Contextual approach to technology assessment: Implications for one-factor fix solutions to complex social problems

    NASA Technical Reports Server (NTRS)

    Mayo, L. H.

    1975-01-01

    The contextual approach is discussed which undertakes to demonstrate that technology assessment assists in the identification of the full range of implications of taking a particular action and facilitates the consideration of alternative means by which the total affected social problem context might be changed by available project options. It is found that the social impacts of an application on participants, institutions, processes, and social interests, and the accompanying interactions may not only induce modifications in the problem contest delineated for examination with respect to the design, operations, regulation, and use of the posited application, but also affect related social problem contexts.

  5. Contextual approach to technology assessment: Implications for one-factor fix solutions to complex social problems

    NASA Technical Reports Server (NTRS)

    Mayo, L. H.

    1975-01-01

    The contextual approach is discussed which undertakes to demonstrate that technology assessment assists in the identification of the full range of implications of taking a particular action and facilitates the consideration of alternative means by which the total affected social problem context might be changed by available project options. It is found that the social impacts of an application on participants, institutions, processes, and social interests, and the accompanying interactions may not only induce modifications in the problem contest delineated for examination with respect to the design, operations, regulation, and use of the posited application, but also affect related social problem contexts.

  6. Injection of sodium borohydride and nzvi solutions into homogeneous sands: H2 gas production and implications

    NASA Astrophysics Data System (ADS)

    Mohammed, O.; Mumford, K. G.; Sleep, B. E.

    2016-12-01

    Gases are commonly introduced into the subsurface via external displacement (drainage). However, gases can also be produced by internal drainage (exsolution). One example is the injection of reactive solutions for in situ groundwater remediation, such as nanoscale zero-valent iron (nzvi), which produces hydrogen gas (H2). Effective implementation of nzvi requires an understanding of H2 gas generation and dynamics, and their effects on aqueous permeability, contaminant mass transfer and potential flow diversion. Several studies have reported using excess sodium borohydride (NaBH4) in nzvi applications to promote complete reaction and to ensure uniform nzvi particle growth, which also produces H2 gas. The aim of this study was to visualize and quantify H2 produced by exsolution from the injection of NaBH4 and nzvi solutions into homogeneous sands, and to investigate the reduction of hydraulic conductivity caused by the H2 gas and the subsequent increase in hydraulic conductivity as the gas dissolved. Bench-scale experiments were performed using cold (4 °C) NaBH4 solutions injected in sand packed in a 22 cm × 34 cm × 1 cm flow cell. The injected solution was allowed to warm to room temperature, for controlled production of a uniform distribution of exsolved gas. A light transmission method was used to quantify gas production and dissolution over time. The results indicate a reduction of hydraulic conductivity due to the existence of H2 and increased hydraulic conductivity as H2 gas dissolves, which could be represented using traditional relative permeability expressions. Additional experiments were performed in the flow cell to compare H2 gas exsolving from nzvi and NaBH4 solutions injected as either a point injection or a well injection. The results indicated greater amounts of H2 gas produced when injecting nzvi solutions prepared with high concentrations of excess NaBH4. H2 gas pooling at the top of the flow cell, and H2 gas trapped near the injection point

  7. Enantioselective sorption of the chiral fungicide metalaxyl on soil from non-racemic aqueous solutions: Environmental implications.

    PubMed

    Celis, Rafael; Gámiz, Beatriz; Facenda, Gracia; Hermosín, María C

    2015-12-30

    Mechanisms governing the enantioselectivity of the processes that determine the behavior of chiral pollutants in the environment need to be better understood. Understanding these mechanisms should help improve predictions of the hazards and risks chiral compounds can pose to people and the environment. We report the results of batch sorption experiments indicating that the sorption of the chiral fungicide metalaxyl on soil from non-racemic initial solutions was enantioselective. While from a racemic initial solution the two enantiomers of metalaxyl were sorbed on the soil to the same extent, increasing the fraction of R-enantiomer in the initial solution led to enhanced sorption of this enantiomer and to reduced sorption of the S-enantiomer. Considering the shape of the sorption isotherms (S-type) and the sorption behavior of model sorbents, we attributed this effect to molecular interactions between metalaxyl enantiomer species at the sorbed state, where R-R metalaxyl interactions appeared to be more favorable than R-S metalaxyl interactions. We discuss important environmental implications of the proposed mechanism, such as those related to the fact that the biological degradation of metalaxyl is known to be an enantioselective process that can yield non-racemic residues in soils shortly after application of the fungicide as a racemic mixture. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. The Thermochemical and Kinetic Properties of Ascorbate are Tuned by its Local Environment: Solution Chemistry and Biochemical Implications

    PubMed Central

    Warren, Jeffrey J.; Mayer, James M.

    2010-01-01

    Ascorbate (Vitamin C) is a ubiquitous biological cofactor. While its aqueous solution chemistry has long been studied, many in vivo reactions of ascorbate occur in enzyme active sites or at membrane interfaces, which have varying local environments. This report shows that the rate and driving force of oxidations of two ascorbate derivatives by the TEMPO radical (2,2′-6,6′-tetramethylpiperidine-1-oxyl) in acetonitrile are very sensitive to the presence of various additives. These reactions proceed by the transfer of a proton and an electron (a hydrogen atom), as is typical of biological ascorbate reactions. The measured rate and equilibrium constants vary substantially with added water or other polar solutes in acetonitrile solutions, indicating large shifts in the reducing power of ascorbate. The correlation of rate and equilibrium constants indicates that this effect has a thermochemical origin rather than being a purely kinetic effect. This contrasts with previous examples of solvent effects on hydrogen atom transfer reactions. Potential biological implications of this apparently unique effect are discussed. PMID:20476757

  9. Tolerability of Oral Xylitol Solution in Young Children: Implications for Otitis Media Prophylaxis

    PubMed Central

    Vernacchio, Louis; Vezina, Richard M.; Mitchell, Allen A.

    2007-01-01

    Objective. Xylitol, given as two grams orally five times-a-day, significantly reduces the incidence of acute otitis media (AOM) in children. A less frequent dosing schedule, if tolerable and efficacious, would promote the more widespread use of this treatment. We sought to determine the tolerability and acceptability in young children of oral xylitol solution at doses of 5 grams three times-a-day (TID) and 7.5 grams once daily (QD). Methods. The study was a three-month randomized placebo-controlled trial of the tolerability and acceptability of oral xylitol solution in 120 children 6-36 months of age performed in the SCOR Network. Results. Study withdrawals and unscheduled medical visits for gastrointestinal complaints did not differ significantly among the study groups. The proportions of subjects in the xylitol TID group who experienced excessive gas or diarrhea at months one, two, and three were 22.7%, 10.0%, and 14.3%, respectively, and in the xylitol QD group were 27.3%, 17.4%, and 14.3%, respectively, and these did not differ from the placebo groups. The proportions who accepted the study solution easily or with only minor difficulty at one, two, and three months in the xylitol TID group were 77.3%, 90.0%, and 90.5% and in the xylitol QD group, 77.3%, 82.6%, and 90.5%, respectively. Conclusions. Oral xylitol solution at dosages of 5 grams TID and 7.5 grams QD is well-tolerated by young children. Given the potential for xylitol as a safe, inexpensive option for AOM prophylaxis, clinical trials using these dosages of xylitol can be conducted. PMID:17097152

  10. Gadofosveset-Based Biomarker of Tissue Albumin Concentration: Technical Validation in Vitro and Feasibility in Vivo

    PubMed Central

    Richardson, Owen C; Bane, Octavia; Scott, Marietta LJ; Tanner, Steven F; Waterton, John C; Sourbron, Steven P; Carroll, Timothy J; Buckley, David L

    2015-01-01

    Purpose There is currently no adequate method of mapping physiologic and pathophysiologic tissue albumin concentrations in human subjects. The objective of this study was to devise and evaluate a biomarker of regional albumin concentration using gadofosveset-enhanced MRI. Theory and Methods A binding and relaxation model was devised and evaluated in vitro in solutions of albumin at 3.0 Tesla (T) and 4.7T. The method was evaluated in the heart in seven volunteers at 3.0T. Results MRI-derived estimates of albumin concentration were in good agreement with true values over the range 0.1–1.0 mM (Pearson correlation coefficients of 0.85 and 0.88 for 3.0T and 4.7T, respectively). The mean calculated albumin concentration in the myocardium for the volunteers was 0.02 mM (range, 0.01–0.03 mM). Conclusion Accurate estimates of albumin concentration in vitro suggest this may be a viable noninvasive alternative to existing techniques. In the myocardium the MRI-derived estimates of albumin concentration indicate the practical feasibility of the technique but were below expected values. Gadofosveset-enhanced MR relaxometry has potential in providing biomarkers of regional albumin concentration; further evaluation is required before it can be used reliably in vivo. Magn Reson Med 73:244–253, 2015. © 2014 Wiley Periodicals, Inc. PMID:24515975

  11. Podocytes Degrade Endocytosed Albumin Primarily in Lysosomes

    PubMed Central

    Carson, John M.; Okamura, Kayo; Wakashin, Hidefumi; McFann, Kim; Dobrinskikh, Evgenia; Kopp, Jeffrey B.; Blaine, Judith

    2014-01-01

    Albuminuria is a strong, independent predictor of chronic kidney disease progression. We hypothesize that podocyte processing of albumin via the lysosome may be an important determinant of podocyte injury and loss. A human urine derived podocyte-like epithelial cell (HUPEC) line was used for in vitro experiments. Albumin uptake was quantified by Western blot after loading HUPECs with fluorescein-labeled (FITC) albumin. Co-localization of albumin with lysosomes was determined by confocal microscopy. Albumin degradation was measured by quantifying FITC-albumin abundance in HUPEC lysates by Western blot. Degradation experiments were repeated using HUPECs treated with chloroquine, a lysosome inhibitor, or MG-132, a proteasome inhibitor. Lysosome activity was measured by fluorescence recovery after photo bleaching (FRAP). Cytokine production was measured by ELISA. Cell death was determined by trypan blue staining. In vivo, staining with lysosome-associated membrane protein-1 (LAMP-1) was performed on tissue from a Denys-Drash trangenic mouse model of nephrotic syndrome. HUPECs endocytosed albumin, which co-localized with lysosomes. Choloroquine, but not MG-132, inhibited albumin degradation, indicating that degradation occurs in lysosomes. Cathepsin B activity, measured by FRAP, significantly decreased in HUPECs exposed to albumin (12.5% of activity in controls) and chloroquine (12.8%), and declined further with exposure to albumin plus chloroquine (8.2%, p<0.05). Cytokine production and cell death were significantly increased in HUPECs exposed to albumin and chloroquine alone, and these effects were potentiated by exposure to albumin plus chloroquine. Compared to wild-type mice, glomerular staining of LAMP-1 was significantly increased in Denys-Drash mice and appeared to be most prominent in podocytes. These data suggest lysosomes are involved in the processing of endocytosed albumin in podocytes, and lysosomal dysfunction may contribute to podocyte injury and

  12. Albumin reduces the antibacterial efficacy of wound antiseptics against Staphylococcus aureus.

    PubMed

    Kapalschinski, N; Seipp, H M; Kückelhaus, M; Harati, K K; Kolbenschlag, J J; Daigeler, A; Jacobsen, F; Lehnhardt, M; Hirsch, T

    2017-04-02

    The influence of proteins on the efficacy of antiseptic solutions has been rarely investigated even though exudate can contain high levels of protien. The aim of this study was to analyse the antibacterial efficacy of commonly used solutions in the presence of albumin protein. Using Staphylococcus aureus in a standardised quantitative suspension assay, the antibacterial effects of poly (1-(2-oxo-1-pyrrolidinyl) ethylene)-iodine (PVP-I) and octenidin-dihydrochloride/phenoxyethanol (OCT/PE) were analysed in the presence of 0-3% bovine serum albumin (BSA). These were compared with previous results obtained with polyhexamethylene biguanide hydrochloride (PHMB). Presence of albumin caused a significant (p<0.001) decrease in antibacterial effect in the analysed solutions. The concentrations of albumin that provoked highly significant decreases in the bacterial reduction factors of the study agents were: 0.01875 % for PVP-I, followed by 0.75 % for OCT/PE. After addition of 3 % albumin, adequate antimicrobial effects were ensured for titrations to 5 % PVP-I and 8 % OCT/PE. As we could show before, it is not possible to titrate PHMB in order to assure adequate potency. This study demonstrates that albumin induces a significant decrease of the antibacterial potency of the analysed solutions.

  13. Effects of albumin 5% and artificial colloids on clot formation in small infants.

    PubMed

    Haas, T; Preinreich, A; Oswald, E; Pajk, W; Berger, J; Kuehbacher, G; Innerhofer, P

    2007-10-01

    Albumin is often cited in textbooks as the gold standard for fluid replacement in paediatrics, but in practice artificial colloids are more frequently used. Although one concern with the use of artificial colloids is their intrinsic action on haemostasis, the available data in children are inconclusive for 6% hydroxyethyl starch 130/0.4 (HES) and no data exist for gelatine solution with respect to coagulation. A total of 42 children (3-15 kg) undergoing surgery and needing colloid replacement were randomly assigned to receive 15 mlxkg(-1) of either albumin 5%, 4% modified gelatine solution or 6% hydroxyethyl starch 130/0.4 solution. Standard coagulation tests and modified thrombelastography (ROTEM) were performed. After colloid administration, routine coagulation test results changed significantly and comparably in all groups, although activated partial thromboplastin time values increased more with gelatine and HES. Coagulation time was unchanged in the children who received albumin or gelatine but other activated modified thrombelastography values were significantly impaired in all groups. After gelatine and after albumin the median clot firmness decreased significantly but remained within the normal range. Following HES, coagulation time increased significantly, and clot formation time, alpha angle, clot firmness, and fibrinogen/fibrin polymerisation were significantly more impaired than for albumin or gelatine, reaching median values below the normal range. From a haemostatic point of view it might be preferable to use gelatine solution as an alternative to albumin; HES showed the greatest effects on the overall coagulation process.

  14. Chromatographic evidence of the self-association of oxyhemoglobin in concentrated solutions: its biological implications.

    PubMed

    Nichol, L W; Siezen, R J; Winzor, D J

    1979-07-01

    Expressions that take into account the effects of thermodynamic non-ideality, described in terms of a high-order virial expansion, are derived for the concentration-dependence of the weight-average partition coefficient in exclusion chromatography of a single solute and of a solute undergoing reversible self-association. Comparison of the concentration-dependences predicted by those expressions with results obtained for bovine and human oxyhemoglobins on CPG-10-120 porous glass beads in 0.156 I phosphate-chloride buffer, pH 7.3, shows that neither oxyhemoglobin conforms with the concept of it being a single alpha 2 beta 2 entity with Stokes radius of 3.13 nm, the experimental value. Previously published osmotic pressure and sedimentation equilibrium results are also shown to be inconsistent with this concept. On the other hand, both sets of exclusion chromatography results are consistent with the joint operation of thermodynamic non-ideality and reversible association of the alpha 2 beta 2 species. From the magnitude of the equilibrium constant, derived for either of two possible modes of association, it is calculated that only half of the oxyhemoglobin would be in the alpha 2 beta 2 states under conditions of oxygen saturation and a concentration of 320 g/liter, that pertaining in the red blood cell. The consequences of this association phenomenon are discussed in relation to the oxygen binding curves obtained by others in the presence and absence of 2,3-diphosphoglycerate (DPG). An explanation is provided of the observed dependence on hemoglobin concentration of oxygen-binding in the presence of DPG, and of the absence of such an effect in DPG-free solutions. It is concluded that the control of oxygen binding to hemoglobin in the physiological situation involves the joint operation of self-association and allosteric effects.

  15. Bioavailability and ecotoxicity of arsenic species in solution culture and soil system: implications to remediation.

    PubMed

    Bolan, Nanthi; Mahimairaja, Santiago; Kunhikrishnan, Anitha; Seshadri, Balaji; Thangarajan, Ramya

    2015-06-01

    In this work, bioavailability and ecotoxicity of arsenite (As(III)) and arsenate (As(V)) species were compared between solution culture and soil system. Firstly, the adsorption of As(III) and As(V) was compared using a number of non-allophanic and allophanic soils. Secondly, the bioavailability and ecotoxicity were examined using germination, phytoavailability, earthworm, and soil microbial activity tests. Both As-spiked soils and As-contaminated sheep dip soils were used to test bioavailability and ecotoxicity. The sheep dip soil which contained predominantly As(V) species was subject to flooding to reduce As(V) to As(III) and then used along with the control treatment soil to compare the bioavailability between As species. Adsorption of As(V) was much higher than that of As(III), and the difference in adsorption between these two species was more pronounced in the allophanic than non-allophanic soils. In the solution culture, there was no significant difference in bioavailability and ecotoxicity, as measured by germination and phytoavailability tests, between these two As species. Whereas in the As-spiked soils, the bioavailability and ecotoxicity were higher for As(III) than As(V), and the difference was more pronounced in the allophanic than non-allophanic soils. Bioavailability of As increased with the flooding of the sheep dip soils which may be attributed to the reduction of As(V) to As(III) species. The results in this study have demonstrated that while in solution, the bioavailability and ecotoxicity do not vary between As(III) and As(V), in soils, the latter species is less bioavailable than the former species because As(V) is more strongly retained than As(III). Since the bioavailability and ecotoxicity of As depend on the nature of As species present in the environment, risk-based remediation approach should aim at controlling the dynamics of As transformation.

  16. The ubiquitous nature of accessory calcite in granitoid rocks: Implications for weathering, solute evolution, and petrogenesis

    USGS Publications Warehouse

    White, A.F.; Schulz, M.S.; Lowenstern, J. B.; Vivit, D.V.; Bullen, T.D.

    2005-01-01

    Calcite is frequently cited as a source of excess Ca, Sr and alkalinity in solutes discharging from silicate terrains yet, no previous effort has been made to assess systematically the overall abundance, composition and petrogenesis of accessory calcite in granitoid rocks. This study addresses this issue by analyzing a worldwide distribution of more than 100 granitoid rocks. Calcite is found to be universally present in a concentration range between 0.028 to 18.8 g kg-1 (mean = 2.52 g kg-1). Calcite occurrences include small to large isolated anhedral grains, fracture and cavity infillings, and sericitized cores of plagioclase. No correlation exists between the amount of calcite present and major rock oxide compositions, including CaO. Ion microprobe analyses of in situ calcite grains indicate relatively low Sr (120 to 660 ppm), negligible Rb and 87Sr/86Sr ratios equal to or higher than those of coexisting plagioclase. Solutes, including Ca and alkalinity produced by batch leaching of the granitoid rocks (5% CO2 in DI water for 75 d at 25??C), are dominated by the dissolution of calcite relative to silicate minerals. The correlation of these parameters with higher calcite concentrations decreases as leachates approach thermodynamic saturation. In longer term column experiments (1.5 yr), reactive calcite becomes exhausted, solute Ca and Sr become controlled by feldspar dissolution and 87Sr/ 86Sr by biotite oxidation. Some accessory calcite in granitoid rocks is related to intrusion into carbonate wall rock or produced by later hydrothermal alteration. However, the ubiquitous occurrence of calcite also suggests formation during late stage (subsolidus) magmatic processes. This conclusion is supported by petrographic observations and 87Sr/86Sr analyses. A review of thermodynamic data indicates that at moderate pressures and reasonable CO2 fugacities, calcite is a stable phase at temperatures of 400 to 700??C. Copyright ?? 2005 Elsevier Ltd.

  17. Complexation of serum albumins and triton X-100: Quenching of tryptophan fluorescence and analysis of the rotational diffusion of complexes

    NASA Astrophysics Data System (ADS)

    Vlasova, I. M.; Vlasov, A. A.; Saletskii, A. M.

    2016-07-01

    The polarized and nonpolarized fluorescence of bovine serum albumin and human serum albumin in Triton X-100 solutions is studied at different pH values. Analysis of the constants of fluorescence quenching for BSA and HSA after adding Triton X-100 and the hydrodynamic radii of BSA/HSA-detergent complexes show that the most effective complexation between both serum albumins and Triton X-100 occurs at pH 5.0, which lies near the isoelectric points of the proteins. Complexation between albumin and Triton X-100 affects the fluorescence of the Trp-214 residing in the hydrophobic pockets of both BSA and HSA.

  18. The effects of haemodilution with albumin on coagulation in vitro as assessed by rotational thromboelastometry.

    PubMed

    Pathirana, S; Wong, G; Williams, P; Yang, K; Kershaw, G; Dunkley, S; Kam, P C A

    2015-03-01

    We investigated the in vitro viscoelastic changes of progressive haemodilution with 4% albumin compared with normal saline (NS) using rotational thromboelastometry (ROTEM(®), Pentapharm Co., Munich, Germany). Whole blood samples obtained from 20 healthy volunteers were diluted in vitro with 4% albumin or NS by 10%, 20% and 40%. Fibrinogen concentration and ROTEM(®) (EXTEM [screening test for the extrinsic haemostasis system], FIBTEM [EXTEM-based assay for the fibrin part of the clot]) variables including coagulation time, clot formation time (CFT), α-angle, maximum clot firmness and lysis index were measured in the undiluted sample and at each degree of haemodilution. There was no significant difference in fibrinogen concentration at equivalent haemodilutions with normal saline and 4% albumin solutions. Forty percent haemodilution with albumin significantly prolonged coagulation time (EXTEM P=0.007, FIBTEM P=0.0001) and significantly decreased lysis index (FIBTEM P=0.009) compared with NS. A significant decrease in maximum clot firmness from undiluted measurements (P=0.05) was observed at lower haemodilutions with albumin (20% with EXTEM, 10% with FIBTEM) compared with NS (40% with EXTEM and FIBTEM). The adverse effects of large degrees of haemodilution with 4% albumin solution are in excess of what can be explained by haemodilution alone. This study suggests that large degrees of haemodilution with albumin impair fibrinogen activity to a greater extent than equivalent degrees of haemodilution with NS.

  19. Structure of Glycine Dihyrate: Its Implications to Crystallization of Glycine from Solution and Modification of Clycine in Space

    SciTech Connect

    Xu, Wenqian; Zhu, Qiang; Hu, Chunhua

    2017-01-01

    Glycine, the simplest amino acid, is also the most polymorphous. Herein, we report the structure determination of an unknown phase of glycine which was firstly reported by Pyne and Suryanarayanan in 2001. To date, the new phase has only been prepared at 208 K as nanocrystals within ice. Through computational crystal structure prediction and powder X-ray diffraction methods, we identified this elusive phase as glycine dihydrate (GDH), representing a first report on a hydrated glycine structure. The structure of GDH has important implications for the state of glycine in aqueous solution, and the mechanisms of glycine crystallization. GDH may also be the form of glycine that comes to Earth from extraterrestrial sources.

  20. Mechanistic and conformational studies on the interaction of a platinum(II) complex containing an antiepileptic drug, levetiracetam, with bovine serum albumin by optical spectroscopic techniques in aqueous solution.

    PubMed

    Shahabadi, Nahid; Hadidi, Saba

    2015-02-01

    Fluorescence spectroscopy in combination with circular dichroism (CD) and ultraviolet-visible (UV-vis) absorption spectroscopy were employed to investigate the binding of a new platinum(II) complex containing an antiepileptic drug "Levetiracetam" to bovine serum albumin (BSA) under the physiological conditions. In the mechanism discussion, it was proved that the fluorescence quenching of BSA by Pt(II) complex is a result of the formation of Pt(II) complex-BSA complex. The thermodynamic parameters ΔG, ΔH, and ΔS at different temperatures (283, 298, and 310 K) were calculated, and the negative value for ΔH and ΔS indicate that the hydrogen bonds and van der Waals interactions play major roles in Pt(II) complex-BSA association. Binding studies concerning the number of binding sites (n~1) and apparent binding constant K b were performed by fluorescence quenching method. The site marker competitive experiments indicated that the binding of Pt(II) complex to BSA primarily took place in site II. Based on the Förster's theory, the average binding distance between Pt(II) complex and BSA was obtained (r = 5.29 nm). Furthermore, UV-vis, CD, and synchronous fluorescence spectrum were used to investigate the structural change of BSA molecules with addition of Pt(II) complex. These results indicate that the binding of Pt(II) complex to BSA causes apparent change in the secondary structure of BSA and do affect the microenvironment around the tryptophan residue.

  1. Experimental calibration of Mg isotope fractionation between dolomite and aqueous solution and its geological implications

    NASA Astrophysics Data System (ADS)

    Li, Weiqiang; Beard, Brian L.; Li, Chengxiang; Xu, Huifang; Johnson, Clark M.

    2015-05-01

    Hydrothermal experiments at 220, 160, and 130 °C were performed to calibrate the Mg isotope fractionation factor between dolomite and aqueous Mg. Hydrothermal experiments included synthesis of dolomite using different starting materials, as well as exchange experiments that used poorly-ordered proto-dolomite. The morphology of synthesized dolomite was dependent on starting mineralogy, suggesting that dolomite was synthesized by different pathways. Hydrothermally synthesized dolomite was initially fine-grained disordered or poorly-ordered dolomite that, with time, recrystallized to coarser-grained ordered dolomite. Isotopic exchange was monitored using 87Sr/86Sr ratios and 25Mg tracers, and these indicated near-complete isotope exchange between dolomite and aqueous solutions at the end of most hydrothermal experiments. The Mg isotope fractionation factor between dolomite and aqueous solution obtained from synthesis and exchange experiments converged with time and was independent of dolomite morphology, suggesting attainment of isotopic equilibrium. Combining results from synthesis and exchange experiments, the temperature dependent Mg isotope fractionation factor for ordered dolomite is:

  2. Organics Produced by Irradiation of Frozen and Liquid HCN Solutions: Implications for Chemical Evolution Studies

    NASA Astrophysics Data System (ADS)

    Colín-García, M.; Negrón-Mendoza, A.; Ramos-Bernal, S.

    2009-04-01

    Hydrogen cyanide (HCN), an important precursor of organic compounds, is widely present in extraterrestrial environments. HCN is also readily synthesized in prebiotic simulation experiments. To gain insight into the radiation chemistry of one of the most important and highly versatile constituents of cometary ices, we examined the behavior of over-irradiated frozen and liquid HCN solutions under ionizing radiation. The samples were exposed to gamma radiation at a dose range from 0 up to 419 kGy. Ultraviolet spectroscopy and gas chromatography were used to follow the process. The analyses confirmed that gamma-ray irradiation of liquid HCN solutions generates several organic products. Many of them are essential to life; we verified the presence of carboxylic acids (some of them members of the Krebs cycle) as well as free amino acids and urea. These are the first studies to reveal the presence of these compounds in experiments performed at low temperatures and bulk irradiation. Organic material was produced even at low temperatures and low radiation doses. This work strongly supports the presumption that, as a parent molecule, HCN played a central essential role in the process of chemical evolution on early Earth, comets, and other extraterrestrial environments.

  3. Crystal Structure of a Bacterial Albumin-Binding Domain at 1.4 Angstrom Resolution

    SciTech Connect

    Cramer, J.F.; Nordberg, P.A.; Hajdu, J.; Lejon, S.; /Uppsala U. /Aalborg U. /Astra Tech, Molndal /SLAC

    2007-11-26

    The albumin-binding domain, or GA module, of the peptostreptococcal albumin-binding protein expressed in pathogenic strains of Finegoldia magna is believed to be responsible for the virulence and increased growth rate of these strains. Here we present the 1.4 Angstrom crystal structure of this domain, and compare it with the crystal structure of the GA-albumin complex. An analysis of protein-protein interactions in the two crystals, and the presence of multimeric GA species in solution, indicate the GA module is 'sticky', and is capable of forming contacts with a range of protein surfaces. This might lead to interactions with different host proteins.

  4. Crystals of Serum Albumin for Use in Genetic Engineering and Rational Drug Design

    NASA Technical Reports Server (NTRS)

    Carter, Daniel C. (Inventor)

    1996-01-01

    Serum albumin crystal forms have been produced which exhibit superior x-ray diffraction quality. The crystals are produced from both recombinant and wild-type human serum albumin, canine, and baboon serum albumin and allow the performance of drug-binding studies as well as genetic engineering studies. The crystals are grown from solutions of polyethylene glycol or ammonium sulphate within prescribed limits during growth times from one to several weeks and include the following space groups: P2(sub 1), C2, P1.

  5. Binding interactions of pefloxacin mesylate with bovine lactoferrin and human serum albumin*

    PubMed Central

    Fan, Ji-cai; Chen, Xiang; Wang, Yun; Fan, Cheng-ping; Shang, Zhi-cai

    2006-01-01

    The binding of pefloxacin mesylate (PFLX) to bovine lactoferrin (BLf) and human serum albumin (HSA) in dilute aqueous solution was studied using fluorescence spectra and absorbance spectra. The binding constant K and the binding sites n were obtained by fluorescence quenching method. The binding distance r and energy-transfer efficiency E between pefloxacin mesylate and bovine lactoferrin as well as human serum albumin were also obtained according to the mechanism of Förster-type dipole-dipole nonradiative energy-transfer. The effects of pefloxacin mesylate on the conformations of bovine lactoferrin and human serum albumin were also analyzed using synchronous fluorescence spectroscopy. PMID:16691639

  6. Albumin impacts the effects of tonicity on microvascular hydraulic permeability.

    PubMed

    Victorino, Gregory P; Chong, Terry J; Curran, Brian

    2004-12-01

    An increase in tonicity shrinks endothelial cells. This cell shrinkage may open inter-endothelial gaps and allow more fluid to escape from the microvasculature. This increase in microvascular permeability is not supported by clinical studies suggesting that water is pulled into the vascular space, not lost into the interstitium. We hypothesized that albumin influences the change in trans-endothelial water movement caused by alterations in tonicity by a mechanism other than oncotic pressure. Hydraulic permeability (L(p)) was measured in rat mesenteric venules using the Landis micro-occlusion model. Measures of L(p) were obtained after successive perfusions with 1% albumin solution (BSA) of varying sodium chloride (NaCl) concentrations (85, 135, 185, and 235 mm) (n = 6). Additional venules were perfused with 7% NaCl followed by 7% NaCl + BSA and L(p) measured (n = 6). Units for L(p) are x10(-7) cm/sec(-1) cm/H(2)O(-1). As the NaCl concentration in BSA increased from 85 mm to 235 mm, L(p) decreased from 1.93 +/- 0.41 to 0.97 +/- 0.11. Compared to results without albumin, BSA with 185 mm NaCl decreased L(p) from 3.93 +/- 0.08 to 1.25 +/- 0.18 (P = 0.04), and BSA with 235 mm NaCl decreased L(p) from 6.14 +/- 0.05 to 0.96 +/- 0.11 (P = 0.002). There was a three-fold decrease in L(p) when BSA was added to the 7% NaCl solution (P = 0.02). Albumin attenuated the increase in L(p) that is associated with higher NaCl concentrations. Because this model controls for oncotic pressure, albumin may impact L(p) by a mechanism other than oncotic force. Albumin appears to stabilize the endothelial barrier during HS perfusion and prevents the loss of intravascular fluid. Appropriate albumin levels may play an important clinical role in modulating trans-endothelial fluid efflux during HS administration.

  7. Property Changes in Aqueous Solutions due to Surfactant Treatment of PCE: Implications to Geophysical Measurements

    NASA Astrophysics Data System (ADS)

    Werkema, D. D.

    2007-12-01

    Select physicochemical properties of aqueous solutions composed of surfactants, dye, and perchloroethylene (PCE) were evaluated through a response surface quadratic design model of experiment. Nine surfactants, which are conventionally used in the remediation of PCE, were evaluated with varying concentrations of PCE and indicator dyes in aqueous solutions. Two hundred forty experiments were performed using PCE as a numerical factor (coded A) from 0 to 200 parts per million (ppm), dye type (coded B) as a 3-level categorical factor, and surfactant type (coded C) as a 10-level categorical factor. Five responses were measured: temperature (°C), pH, conductivity (μS/cm), dissolved oxygen (DO, mg/L), and density (g/mL). Diagnostics proved a normally distributed predictable response for all measured responses except pH. The Box-Cox plot for transforms recommended a power transform for the conductivity response with lambda (λ) = 0.50, and for the DO response, λ =2.2. The overall mean of the temperature response proved to be a better predictor than the linear model. The conductivity response is best fitted with a linear model using significant coded terms B and C. Both DO and density also showed a linear model with coded terms A, B, and C for DO; and terms A and C for density. Some of the surfactant treatments of PCE significantly alter the conductivity, DO, and density of the aqueous solution. However, the magnitude of the density response is so small that it does not exceed the instrument tolerance. Results for the conductivity and DO responses provide predictive models for the surfactant treatment of PCE and may be useful in determining the potential for geophysically monitoring surfactant enhanced aquifer remediation (SEAR) of PCE. As the aqueous physicochemical properties change due to surfactant remediation efforts, so will the properties of the subsurface pore water which are influential factors in geophysical measurements. Geoelectrical methods are potentially

  8. Freezing of sulfuric and nitric acid solutions: Implications for polar stratospheric cloud formation

    NASA Astrophysics Data System (ADS)

    Salcedo Gonzalez, Dara

    2000-12-01

    Polar Stratospheric Clouds (PSCs) play an important role in ozone chemistry during the polar winter. The magnitude of their effect depends on their phase, composition and formation mechanism, which are not fully understood yet. In order to understand how liquid PSCs freeze, two apparatus were designed to study the freezing behavior of small drops using a Fourier transform infrared (FTIR) spectrometer and an optical microscope. Sulfuric acid aqueous drops with composition of 10 to 50 wt % were studied with the FTIR apparatus. The surface on which the drops stand caused heterogeneous nucleation of ice, but not of the sulfuric acid hydrates. The more concentrated solutions (>40 wt %) supercooled to 130 K without freezing. Below 150 K these solutions formed an amorphous solid, which liquefied upon warming. Drops with composition of 40 to 64 wt % HNO3 were prepared and their phase transitions were detected with the optical microscope apparatus. Freezing temperatures of the drops were determined and homogeneous nucleation rates of nitric acid dihydrate (JNAD) and nitric acid trihydrate (JNAT) between 170 and 190 K were calculated. JNAT and JNAD depend predominantly on the saturation of the solid in the liquid solution: higher saturation ratios correspond to higher nucleation rates. Classical nucleation theory was used to parameterize this relation. Since the saturation ratios of NAD and NAT vary with temperature and composition in different ways, NAT or NAD can form preferentially under different conditions. Evidence was found that NAD catalyzes the nucleation of NAT below ~183 K. Mullite, cristobalite and alumina were tested as possible heterogeneous nuclei of volcanic origin for PSCs. They catalyze freezing of NAD and NAT at temperatures below 179 K, which are too low to be stratospherically important. The results suggest that the largest drops in a PSC will freeze homogeneously if the stratospheric temperature remains below the NAT condensation temperature for more

  9. Comparative Study of Laterite and Bentonite Based Organoclays: Implications of Hydrophobic Compounds Remediation from Aqueous Solutions

    PubMed Central

    Nafees, Muhammad; Waseem, Amir; Khan, Abdur Rehman

    2013-01-01

    Four cost effective organoclays were synthesized, characterized, and studied for the sorption of hydrophobic compounds (edible oil/grease and hydrocarbon oil) from aqueous solutions. Organoclays were prepared by cation exchange reaction of lattice ions (present onto the surface of laterite and bentonite clay minerals) with two surfactants, hexadecyl trimethyl ammonium chloride (HDTMA-Cl) and tetradecyl trimethyl ammonium bromide (TDTMA-Br). Fourier transform infrared spectroscopy and scanning electron microscopy were used for the characterization of synthesized organoclays. It was found that the amount of surfactant loading and the nature of the surfactant molecules used in the syntheses of organoclay strongly affect the sorption capacity of the clay mineral. Further, it was found that both the laterite and bentonite based organoclays efficiently removed the edible and hydrocarbon oil content from lab prepared emulsions; however, the adsorption capacity of clay mineral was greatly influenced by the nature of hydrophobic compounds as well. PMID:24302867

  10. Comparative study of laterite and bentonite based organoclays: implications of hydrophobic compounds remediation from aqueous solutions.

    PubMed

    Nafees, Muhammad; Waseem, Amir; Khan, Abdur Rehman

    2013-01-01

    Four cost effective organoclays were synthesized, characterized, and studied for the sorption of hydrophobic compounds (edible oil/grease and hydrocarbon oil) from aqueous solutions. Organoclays were prepared by cation exchange reaction of lattice ions (present onto the surface of laterite and bentonite clay minerals) with two surfactants, hexadecyl trimethyl ammonium chloride (HDTMA-Cl) and tetradecyl trimethyl ammonium bromide (TDTMA-Br). Fourier transform infrared spectroscopy and scanning electron microscopy were used for the characterization of synthesized organoclays. It was found that the amount of surfactant loading and the nature of the surfactant molecules used in the syntheses of organoclay strongly affect the sorption capacity of the clay mineral. Further, it was found that both the laterite and bentonite based organoclays efficiently removed the edible and hydrocarbon oil content from lab prepared emulsions; however, the adsorption capacity of clay mineral was greatly influenced by the nature of hydrophobic compounds as well.

  11. Concentration gradients at the mineral-solution interface: implications for understanding dissolution mechanisms

    NASA Astrophysics Data System (ADS)

    Ruiz-Agudo, Encarnacion; Patiño-López, Luis David; Putnis, Christine V.; Rodriguez-Navarro, Carlos; Putnis, Andrew

    2014-05-01

    Dissolution is a key process in fluid-rock interactions, such as in chemical weathering, CO2 carbonation reactions, metasomatism, and metamorphism. Many multicomponent rock-forming minerals are reported to dissolve incongruently, because the elemental molar ratios, measured in the fluid during dissolution experiments, that differ from those in the solid. This frequently results in the formation of chemically and structurally altered zones at the fluid-solid interface of varying thickness that are depleted in some elements relative to the bulk mineral composition. Although the mechanisms of the formation of these altered layers is still a matter of debate (see e.g. Ruiz-Agudo et al. 2012 and Schott et al. 2012), recent AFM studies on the dissolution of two multicomponent minerals, dolomite, Ca0.5Mg0.5CO3 (Urosevic et al. 2012), and wollastonite, CaSiO3 (Ruiz-Agudo et al. 2012), provide experimental evidence showing that these layers are formed in a two-step process: (i) stoichiometric dissolution of the pristine mineral surfaces and (ii) precipitation of a secondary phase. This occurs despite the fact that the bulk solution is undersaturated with respect to such a phase. It has been suggested that after stoichiometric dissolution of the mineral, a boundary layer of fluid in contact with the surface becomes supersaturated with respect to a secondary phase that then precipitates. Here we present in situ observations of the evolution of the fluid composition at the interface during dissolution in acidic solutions (pH 1.5) of dolomite and wollastonite using real-time phase-shift interferometry. We show that immediately when the sparingly soluble dolomite or wollastonite crystals are in contact with the solution, the refractive index of the solution at the crystal surface sharply increases. A steep refractive index gradient (i.e., concentration gradient) develops as a consequence of mineral dissolution producing an interfacial fluid with a different composition to the

  12. Hierarchical simulation of aquifer heterogeneity: implications of different simulation settings on solute-transport modeling

    NASA Astrophysics Data System (ADS)

    Comunian, Alessandro; De Micheli, Leonardo; Lazzati, Claudio; Felletti, Fabrizio; Giacobbo, Francesca; Giudici, Mauro; Bersezio, Riccardo

    2016-03-01

    The fine-scale heterogeneity of porous media affects the large-scale transport of solutes and contaminants in groundwater and it can be reproduced by means of several geostatistical simulation tools. However, including the available geological information in these tools is often cumbersome. A hierarchical simulation procedure based on a binary tree is proposed and tested on two real-world blocks of alluvial sediments, of a few cubic meters volume, that represent small-scale aquifer analogs. The procedure is implemented using the sequential indicator simulation, but it is so general that it can be adapted to various geostatistical simulation tools, improving their capability to incorporate geological information, i.e., the sedimentological and architectural characterization of heterogeneity. When compared with a standard sequential indicator approach on bi-dimensional simulations, in terms of proportions and connectivity indicators, the proposed procedure yields reliable results, closer to the reference observations. Different ensembles of three-dimensional simulations based on different hierarchical sequences are used to perform numerical experiments of conservative solute transport and to obtain ensembles of equivalent pore velocity and dispersion coefficient at the scale length of the blocks (meter). Their statistics are used to estimate the impact of the variability of the transport properties of the simulated blocks on contaminant transport modeled on bigger domains (hectometer). This is investigated with a one-dimensional transport modeling based on the Kolmogorov-Dmitriev theory of branching stochastic processes. Applying the proposed approach with diverse binary trees and different simulation settings provides a great flexibility, which is revealed by the differences in the breakthrough curves.

  13. Antioxidant flavonoids bind human serum albumin

    NASA Astrophysics Data System (ADS)

    Kanakis, C. D.; Tarantilis, P. A.; Polissiou, M. G.; Diamantoglou, S.; Tajmir-Riahi, H. A.

    2006-10-01

    Human serum albumin (HSA) is a principal extracellular protein with a high concentration in blood plasma and carrier for many drugs to different molecular targets. Flavonoids are powerful antioxidants and prevent DNA damage. The antioxidative protections are related to their binding modes to DNA duplex and complexation with free radicals in vivo. However, flavonoids are known to inhibit the activities of several enzymes such as calcium phospholipid-dependent protein kinase, tyrosine protein kinase from rat lung, phosphorylase kinase, phosphatidylinositol 3-kinase and DNA topoisomerases that exhibit the importance of flavonoid-protein interaction. This study was designed to examine the interaction of human serum albumin (HSA) with quercetin (que), kaempferol (kae) and delphinidin (del) in aqueous solution at physiological conditions, using constant protein concentration of 0.25 mM (final) and various drug contents of 1 μM-1 mM. FTIR and UV-vis spectroscopic methods were used to determine the polyphenolic binding mode, the binding constant and the effects of flavonoid complexation on protein secondary structure. The spectroscopic results showed that flavonoids are located along the polypeptide chains through H-bonding interactions with overall affinity constant of Kque = 1.4 × 10 4 M -1, Kkae = 2.6 × 10 5 M -1 and Kdel = 4.71 × 10 5 M -1. The protein secondary structure showed no alterations at low pigment concentration (1 μM), whereas at high flavonoid content (1 mM), major reduction of α-helix from 55% (free HSA) to 42-46% and increase of β-sheet from 15% (free HSA) to 17-19% and β-anti from 7% (free HSA) to 10-20% occurred in the flavonoid-HSA adducts. The major reduction of HSA α-helix is indicative of a partial protein unfolding upon flavonoid interaction.

  14. Albumin modulates S1P delivery from red blood cells in perfused microvessels: mechanism of the protein effect.

    PubMed

    Adamson, R H; Clark, J F; Radeva, M; Kheirolomoom, A; Ferrara, K W; Curry, F E

    2014-04-01

    Removal of plasma proteins from perfusates increases vascular permeability. The common interpretation of the action of albumin is that it forms part of the permeability barrier by electrostatic binding to the endothelial glycocalyx. We tested the alternate hypothesis that removal of perfusate albumin in rat venular microvessels decreased the availability of sphingosine-1-phosphate (S1P), which is normally carried in plasma bound to albumin and lipoproteins and is required to maintain stable baseline endothelial barriers (Am J Physiol Heart Circ Physiol 303: H825-H834, 2012). Red blood cells (RBCs) are a primary source of S1P in the normal circulation. We compared apparent albumin permeability coefficients [solute permeability (Ps)] measured using perfusates containing albumin (10 mg/ml, control) and conditioned by 20-min exposure to rat RBCs with Ps when test perfusates were in RBC-conditioned protein-free Ringer solution. The control perfusate S1P concentration (439 ± 46 nM) was near the normal plasma value at 37 °C and established a stable baseline Ps (0.9 ± 0.4 × 10(-6) cm/s). Ringer solution perfusate contained 52 ± 8 nM S1P and increased Ps more than 10-fold (16.1 ± 3.9 × 10(-6) cm/s). Consistent with albumin-dependent transport of S1P from RBCs, S1P concentrations in RBC-conditioned solutions decreased as albumin concentration, hematocrit, and temperature decreased. Protein-free Ringer solution perfusates that used liposomes instead of RBCs as flow markers failed to maintain normal permeability, reproducing the "albumin effect" in these mammalian microvessels. We conclude that the albumin effect depends on the action of albumin to facilitate the release and transport of S1P from RBCs that normally provide a significant amount of S1P to the endothelium.

  15. Overview of Albumin and Its Purification Methods

    PubMed Central

    Raoufinia, Ramin; Mota, Ali; Keyhanvar, Neda; Safari, Fatemeh; Shamekhi, Sara; Abdolalizadeh, Jalal

    2016-01-01

    As the most frequent plasma protein, albumin constitutes more than 50% of the serum proteins in healthy individuals. It has a key role in oncotic pressure maintenance and it is known as a versatile protein carrier for transportation of various endogenous and exogenous ligands. Reduced amounts of albumin in the body will lead to different kinds of diseases such as hypovolemia and hypoproteinemia. It also has various indications in shocks, burns, cardiopulmonary bypass, acute liver failure and etc. Further applications in research consist of cell culture supplement, drug delivery carrier and protein/drug stabilizer. So, the demand for albumin increased annually worldwide. Due to different applications of albumin, many efforts have been accomplished to achieve albumin during a long period of time. In this review, an overview of serum albumin and different purification methods are summarized. PMID:28101456

  16. Solubility of HOBr in Acidic Solution and Implications for Liberation of Halogens Via Aerosol Processing

    NASA Technical Reports Server (NTRS)

    Iraci, Laura T.; Michelsen, R. R.; Rammer, T. A.; Ashbourn, S. F. M.

    2004-01-01

    Halogen species are known to catalytically destroy ozone in several regions of the atmosphere. In addition to direct catalytic losses, bromine compounds can indirectly enhance ozone loss through coupling to other radical families. Hypobromous acid (HOBr) is a key species in the linkage of BrOx to ClOx and HOx. The aqueous- phase coupling reaction HOBr + HCI (right arrow) BrCl + H2O may provide a pathway for chlorine activation on sulfate aerosols at temperatures warmer than those required for polar stratospheric cloud formation. We have measured t h e solubility of HOBr in 45 - 70 wt% sulfuric acid solutions. Over the temperature range 201 - 252 K, HOBr is quite soluble in sulfuric acid, H* = 10(exp 4) - 10(exp 7) mol dm(exp -3) atm(exp -1). The expected inverse dependence of H* on temperature was observed, but only a weak dependence on acidity was found. The solubility of HOBr is comparable to that of HBr, indicating that equilibrium concentrations of HOBr could equal or exceed those of HBr in upper tropospheric and lower stratospheric aerosols. Despite the high solubility of HOBr, aerosol volumes are not large enough to sequester a significant fraction of inorganic bromine from the gas phase. Our measurements of HOBr uptake in aqueous sulfuric acid in the presence of other brominated gases show the evolution of gaseous products including Br2O and Br2.

  17. Solubility of HOBr in Acidic Solution and Implications for Liberation of Halogens Via Aerosol Processing

    NASA Technical Reports Server (NTRS)

    Iraci, Laura T.; Michelsen, R. R.; Rammer, T. A.; Ashbourn, S. F. M.

    2004-01-01

    Halogen species are known to catalytically destroy ozone in several regions of the atmosphere. In addition to direct catalytic losses, bromine compounds can indirectly enhance ozone loss through coupling to other radical families. Hypobromous acid (HOBr) is a key species in the linkage of BrOx to ClOx and HOx. The aqueous- phase coupling reaction HOBr + HCI (right arrow) BrCl + H2O may provide a pathway for chlorine activation on sulfate aerosols at temperatures warmer than those required for polar stratospheric cloud formation. We have measured t h e solubility of HOBr in 45 - 70 wt% sulfuric acid solutions. Over the temperature range 201 - 252 K, HOBr is quite soluble in sulfuric acid, H* = 10(exp 4) - 10(exp 7) mol dm(exp -3) atm(exp -1). The expected inverse dependence of H* on temperature was observed, but only a weak dependence on acidity was found. The solubility of HOBr is comparable to that of HBr, indicating that equilibrium concentrations of HOBr could equal or exceed those of HBr in upper tropospheric and lower stratospheric aerosols. Despite the high solubility of HOBr, aerosol volumes are not large enough to sequester a significant fraction of inorganic bromine from the gas phase. Our measurements of HOBr uptake in aqueous sulfuric acid in the presence of other brominated gases show the evolution of gaseous products including Br2O and Br2.

  18. Effect of encapsulation in the anion receptor pocket of sub-domain IIA of human serum albumin on the modulation of pKa of warfarin and structurally similar acidic guests: a possible implication on biological activity.

    PubMed

    Datta, Shubhashis; Halder, Mintu

    2014-01-05

    Supramolecular and bio-supramolecular host assisted pKa shift of biologically relevant acidic guests, warfarin and coumarin 343, has been monitored using both steady-state and time resolved fluorescence spectroscopy. The anion receptors present in sub-domain IIA of human serum albumin (HSA) stabilize the anionic form of the guest and thereby shift pKa towards acidic range. On the other hand, the preferential binding of the neutral form of guests in the non-polar hydrophobic cavity of β-cyclodextrin results in up-shifted pKa. This shifting of pKa of drugs like warfarin, etc., whose therapeutic activity depends on the position of the acid-base equilibrium in human system, is of great importance in pharmacokinetics. The release of the active form of such drugs from macrocyclic carrier and subsequent distribution through the carrier protein should depend on the modulation of the overall pKa window brought about by the encapsulation in these hosts. Present work also suggests that properly optimized encapsulation in appropriate receptor pocket can enhance the bioavailability of drugs. This work also opens up the possibility to use HSA as encapsulator, instead of traditional cyclodextrins or other polymeric hosts, since such system may overcome toxicity as well as biocompatibility issues.

  19. Efficient solution of large-scale electromagnetic Eigenvalue problems using the implicity restarted Arnoldi method

    SciTech Connect

    White, D; Koning, J

    1999-10-21

    The authors are interested in determining the electromagnetic fields within closed perfectly conducting cavities that may contain dielectric or magnetic materials. The vector Helmholtz equation is the appropriate partial differential equation for this problem. It is well known that the electromagnetic fields in a cavity can be decomposed into distinct modes that oscillate in time at specific resonant frequencies. These modes are referred to as eigenmodes, and the frequencies of these modes are referred to as eigenfrequencies. The authors' present application is the analysis of linear accelerator components. These components may have a complex geometry; hence numerical methods are require to compute the eigenmodes and the eigenfrequencies of these components. The Implicitly Restarted Arnoldi Method (IRAM) is a robust and efficient method for the numerical solution of the generalized eigenproblem Ax = {lambda}Bx, where A and B are sparse matrices, x is an eigenvector, and {lambda} is an eigenvalue. The IRAM is an iterative method for computing extremal eigenvalues; it is an extension of the classic Lanczos method. The mathematical details of the IRAM are too sophisticated to describe here; instead they refer the reader to [1]. A FORTRAN subroutine library that implements various versions of the IRAM is freely available, both in a serial version named ARPACK and parallel version named PARPACK. In this paper they discretize the vector Helmholtz equation using 1st order H(curl) conforming edge elements (also known as Nedelec elements). This discretization results in a generalized eigenvalue problem which can be solved using the IRAM. The question of so-called spurious modes is discussed, and it is shown that applying a spectral transformation completely eliminates these modes, without any need for an additional constraint equation. Typically they use the IRAM to compute a small set (n < 30) of eigenvalues and eigenmodes for a very large systems (N > 100,000).

  20. Frequencies of plasmodesmata in Allium cepa L. roots: implications for solute transport pathways.

    PubMed

    Ma, F; Peterson, C A

    2001-05-01

    Plasmodesmatal frequencies (PFs) were analysed in Allium cepa L. roots with a mature exodermis (100 mm from the tip). For all interfaces within the root, the numbers of plasmodesmata (PD) microm(-2) wall surface (Fw) were calculated from measurements of 60 walls on ultrathin sections. For tissues ranging from the epidermis up to the stelar parenchyma, the frequencies were also expressed as total PD numbers mm(-1) root length (Fn), which is most instructive for considering the radial transport of ions and photosynthates (because the tissues were arranged in concentric cylinders). The Fn values were constantly high at the interfaces of exodermis-central cortex, central cortex-endodermis and endodermis-pericycle (4.05x10(5), 5.13x10(5), and 5.64x10(5), respectively). If the plasmodesmata are functional, a considerable symplastic transport pathway exists between the exodermis and pericycle. Two interfaces had especially low PFs: epidermis-exodermis (Fn=8.96x10(4)) and pericycle-stelar parenchyma (Fn=6.44x10(4)). This suggests that there is significant membrane transport across the interface of epidermis-exodermis (through short cells) and direct transfer of ions from pericycle to protoxylem vessels. In the phloem, the highest PF was detected at the metaphloem sieve element-companion cell interface (Fw=0.42), and all other interfaces had much lower PFs (around 0.10). In the pericycle, the radial walls had a high PF (Fw=0.75), a feature that could permit lateral circulation of solutes, thus facilitating ion (inward) and photosynthate (outward) delivery.

  1. Non-linearity of the collagen triple helix in solution and implications for collagen function.

    PubMed

    Walker, Kenneth T; Nan, Ruodan; Wright, David W; Gor, Jayesh; Bishop, Anthony C; Makhatadze, George I; Brodsky, Barbara; Perkins, Stephen J

    2017-06-16

    Collagen adopts a characteristic supercoiled triple helical conformation which requires a repeating (Xaa-Yaa-Gly)n sequence. Despite the abundance of collagen, a combined experimental and atomistic modelling approach has not so far quantitated the degree of flexibility seen experimentally in the solution structures of collagen triple helices. To address this question, we report an experimental study on the flexibility of varying lengths of collagen triple helical peptides, composed of six, eight, ten and twelve repeats of the most stable Pro-Hyp-Gly (POG) units. In addition, one unblocked peptide, (POG)10unblocked, was compared with the blocked (POG)10 as a control for the significance of end effects. Complementary analytical ultracentrifugation and synchrotron small angle X-ray scattering data showed that the conformations of the longer triple helical peptides were not well explained by a linear structure derived from crystallography. To interpret these data, molecular dynamics simulations were used to generate 50 000 physically realistic collagen structures for each of the helices. These structures were fitted against their respective scattering data to reveal the best fitting structures from this large ensemble of possible helix structures. This curve fitting confirmed a small degree of non-linearity to exist in these best fit triple helices, with the degree of bending approximated as 4-17° from linearity. Our results open the way for further studies of other collagen triple helices with different sequences and stabilities in order to clarify the role of molecular rigidity and flexibility in collagen extracellular and immune function and disease. © 2017 The Author(s).

  2. [Urinary albumin fragmentation and immunoreactivity].

    PubMed

    Kurihara, Yuriko; Nishimaki, Junichi; Nakajima, Toshie; Ida, Takashi; Shiba, Kiyoko

    2009-02-01

    Urinary albumin (ALB) has been measured as a marker for the early detection of diabetic nephropathy. In 2004, Comper et al. developed a gel-filtration high-performance liquid chromatography (HPLC) procedure for the determination of urinary ALB. They demonstrated the presence in its albumin fraction of non immunoreactive ALB with the total molecular weight of a monomeric ALB that was non-reactive with the existing anti-ALB antibody, and reported that the level of urinary non-immunoreactive ALB was higher in diabetic patients than in normal subjects. In this study, we isolated urinary ALB from diabetic patients using an anti-ALB antibody-coupled affinity column to test its immunoreactivity. In some diabetic patients, the results of HPLC and turbidimetric immunoassay for urinary ALB were discrepant. Western blot analysis showed that ALB samples from such patients were contaminated with proteins other than ALB, and contained ALB, whose molecular weight became lower using a reductive procedure. In addition, the reactivity of ALB with anti-ALB antibody differed depending on whether it was in a reduced or non-reduced state. These results indicate that ALB in such patients is susceptible to structural changes due to disease-induced urinary factors and, thus, their urine contains ALB with an altered reactivity to antibody.

  3. Fatty acid binding sites of human and bovine albumins: Differences observed by spin probe ESR

    NASA Astrophysics Data System (ADS)

    Muravsky, Vladimir; Gurachevskaya, Tatjana; Berezenko, Stephen; Schnurr, Kerstin; Gurachevsky, Andrey

    2009-09-01

    Bovine and human serum albumins and recombinant human albumin, all non-covalently complexed with 5- and 16-doxyl stearic acids, were investigated by ESR spectroscopy in solution over a range of pH values (5.5-8.0) and temperatures (25-50 °C), with respect to the allocation and mobility of fatty acid (FA) molecules bound to the proteins and conformation of the binding sites. In all proteins bound FA undergo a permanent intra-albumin migration between the binding sites and inter-domain residence. Nature identity of the recombinant human albumin to its serum-derived analog was observed. However, the binding sites of bovine albumin appeared shorter in length and wider in diameter than those of human albumin. Presumably, less tightly folded domains in bovine albumin allow better penetration of water molecules in the interior of the globule that resulted in higher activation energy of FA dissociation from the binding site. Thus, the sensitive technique based on ESR non-covalent spin labeling allowed quantitative analysis and reliable comparison of the fine features of binding proteins.

  4. Raman microspectroscopy of nanodiamond-induced structural changes in albumin.

    PubMed

    Svetlakova, Anastasiya S; Brandt, Nikolay N; Priezzhev, Alexander V; Chikishev, Andrey Yu

    2015-04-01

    Nanodiamonds (NDs) are promising agents for theranostic applications due to reported low toxicity and high biocompatibility, which is still being extensively tested on cellular, tissue, and organism levels. It is presumed that for experimental and future clinical applications, NDs will be administered into the organism via the blood circulation system. In this regard, the interaction of NDs with blood components needs to be thoroughly studied. We studied the interaction of carboxylated NDs (cNDs) with albumin, one of the major proteins of blood plasma. After 2-h long in vitro incubation in an aqueous solution of the protein, 100-nm cNDs were dried and the dry samples were studied with the aid of Raman microspectroscopy. The spectroscopic data indicate significant conformational changes that can be due to cND–protein interaction. A possible decrease in the functional activity of albumin related to the conformational changes must be taken into account in the in vivo applications.

  5. Raman microspectroscopy of nanodiamond-induced structural changes in albumin

    NASA Astrophysics Data System (ADS)

    Svetlakova, Anastasiya S.; Brandt, Nikolay N.; Priezzhev, Alexander V.; Chikishev, Andrey Yu.

    2015-04-01

    Nanodiamonds (NDs) are promising agents for theranostic applications due to reported low toxicity and high biocompatibility, which is still being extensively tested on cellular, tissue, and organism levels. It is presumed that for experimental and future clinical applications, NDs will be administered into the organism via the blood circulation system. In this regard, the interaction of NDs with blood components needs to be thoroughly studied. We studied the interaction of carboxylated NDs (cNDs) with albumin, one of the major proteins of blood plasma. After 2-h long in vitro incubation in an aqueous solution of the protein, 100-nm cNDs were dried and the dry samples were studied with the aid of Raman microspectroscopy. The spectroscopic data indicate significant conformational changes that can be due to cND-protein interaction. A possible decrease in the functional activity of albumin related to the conformational changes must be taken into account in the in vivo applications.

  6. Cisplatin loaded albumin mesospheres for lung cancer treatment

    PubMed Central

    Lee, Hung-Yen; Mohammed, Kamal A; Goldberg, Eugene P; Kaye, Frederic; Nasreen, Najmunnisa

    2015-01-01

    The low solubility of cisplatin in aqueous solution limits the treatment effectiveness and the application of cisplatin in various kinds of drug-eluting devices. Although cisplatin has a high solubility in Dimethyl sulfoxide (DMSO), the toxicity of cisplatin can be greatly reduced while dissolved in DMSO. In this study, the solid powder of cisplatin-loaded albumin mesospheres (CDDP/DMSO-AMS), in a size range of 1 to 10 µm, were post-loaded with cisplatin and showed high cisplatin content (16% w/w) and effective cytotoxicity to lung cancer cells. Cisplatin were efficiently absorbed into the albumin mesospheres (AMS) in DMSO and, most importantly, the toxicity of cisplatin was remained at 100% after the loading process. This CDDP/DMSO-AMS was designed for the intratumoral injection through the bronchoscopic catheter or dry powder inhalation (DPI) due to its high stability in air or in solution. This CDDP/DMSO-AMS showed a fast cisplatin release within 24 hours. In the in vitro study, CDDP/DMSO-AMS showed high effectiveness on killing the lung cancer cells including the non-small cell lung cancer (NCL-H23 and A549), malignant mesothelioma (CRL-2081) and the mouse lung carcinoma (Lewis lung carcinoma) cell lines. The albumin based mesospheres provide an ideal loading matrix for cisplatin and other metal-based drugs due to the high swelling degree and fast uptake rate in the organic solvents with high polarity. In addition, to investigate the effects of polysaccharides, such as chitosan and chondroitin, on enhancing loading efficiency and lasting cytotoxicity of cisplatin, the polysaccharide-modified albumin mesospheres were synthesized and loaded with cisplatin in this study. PMID:25973300

  7. Ultrasonic frequency analysis for estimating pH in albumin-rich biofluids.

    PubMed

    Rackov, Andrien A; Burns, David H

    2016-01-01

    Ultrasound is known as a non-invasive imaging modality capable of propagating through highly scattering media such as tissue, blood, and other biological fluids, yet currently provides little chemical information. We have developed a straightforward and rapid methodology for estimating pH in albumin-rich biofluids based on analysis of ultrasonic frequencies. Albumin is the most abundant protein in serum and undergoes conformational changes with pH. It was shown that when ultrasound propagated through albumin solutions, the attenuation of collected ultrasound signals increased with pH. By measuring the ultrasound frequency spectra at several albumin concentrations and pH values, the pH of the solutions could be determined by multilinear regression. Differences in absolute protein content contributed to signal differences in the frequency profiles and were minimized through normalization of each spectrum by the sum of all its frequency intensities. This strategy was applied to human serum samples from multiple donors, for which a multilinear regression model was developed with a coefficient of determination (R(2)) of 0.93 and a standard error of estimate (SEE) of 0.08 pH units. The use of albumin as a pH indicator opens the doors for estimations in other albumin-rich media, such as amniotic fluid and cerebrospinal fluid.

  8. Impact of manufacturing improvements on clinical safety of albumin: Australian pharmacovigilance data for 1988-2005.

    PubMed

    Che, Yan; Wilson, Fiona J; Bertolini, Joseph; Schiff, Peter; Maher, Darryl W

    2006-12-01

    To evaluate the impact of manufacturing improvements on the clinical safety of human albumin solutions in Australia. This retrospective study examined the incidence of spontaneously reported post-market adverse drug reactions (ADRs) in Australia associated with successive generations of albumin products manufactured by the Bioplasma Division of CSL Limited (CSL Bioplasma) over 18 years (1988-2005). Key characteristics of each product generation which could affect clinical safety, such as purity, aggregates and prekallikrein activator (PKA) levels, were also identified from CSL batch release records. A total of 3.7 million bottles of iso-oncotic and hyperoncotic albumin products were distributed in Australia over the period. Improvements to manufacturing processes resulted in products with increased albumin purity, lower levels of impurities such as aggregates and PKA, and reduced batch-to-batch variation. The total ADR incidence (number of ADRs per 100 000 bottles distributed) associated with the products currently supplied was 1.5 and 1.7 for Albumex 4 (2VI) and Albumex 20 (2VI), respectively. This was a significant reduction compared with the earlier generation products Stable Plasma Protein Solution (14.1) and 20% Normal Serum Albumin (11.5), respectively (P<0.0001). In particular, hypotensive reactions declined substantially. Post-market pharmacovigilance data collected for successive generations of human albumin products supplied in Australia over 18 years indicates that manufacturing improvements have significantly improved the clinical safety profile of this product.

  9. Evaluation of the influence of albumin on the mineralization of a glass by Atomic Force Microscopy.

    PubMed

    Paiva, A O; Costa, N; Cachinho, S C P; Fernandes, M H V

    2007-04-01

    Bioactive glasses have been used as a graft material that can stimulate the formation of a new bone. In vitro tests usually give sensible indications about the potential bioactivity of these glasses. In the present work the influence of egg albumin on the formation of a Ca-P precipitate on a glass of the system SiO(2)-CaO-MgO-P(2)O(5) was evaluated. The samples were immersed in simulated body fluid (SBF) that simulates the composition of human plasma, with and without albumin. After immersion in this solution for 7 and 14 days, the glass was characterized by X-Ray Diffraction (XRD) and Atomic Force Microscopy (AFM). AFM results of the samples after immersion in SBF with albumin show the development of a precipiate formed from the solution/substrate reaction. Glasses immersed in albumin-free SBF exhibit the formation of a thin layer easily detached from the substrate. XRD results indicate that the precipitate is essentially amorphous, evolving to octacalcium phosphate. As the formation of an adherent precipitate on the glass samples only occurred when the substrate was immersed in SBF with albumin, it is suggested that albumin improves the mineralization on the glasses.

  10. [Spectral and fluorescent study of the interaction of squarylium dyes, derivatives of 3H-indolium, with albumins].

    PubMed

    Tatikolov, A S; Panova, I G; Ishchenko, A A; Kudinova, M A

    2010-01-01

    Noncovalent interactions of intraionic squarylium dyes, derivatives of 3H-indolium, as well as the structurally analogous ionic indodicarbocyanine dye with serum albumins (human, bovine, rat) and, for comparison, with ovalbumin has been studied by spectral and fluorescent methods. The hydrophilic squarylium dye with sulfonate groups was found to interact with albumins more efficiently, which is probably due to the double negative charge on the dye molecule at the expense of the sulfonate groups and the ability to form hydrogen bonds with albumin. The hydrophilic indodicarbocyanine dye without the squarylium group in its structure binds to albumins much more weaker than the structurally analogous squarylium dye. The dyes bind to ovalbumin less efficiently than to serum albumins. Along with the binding of monomeric dye molecules, the aggregation of the dyes on albumins is also observed. The hydrophobic squarylium dye without sulfonate groups tends to form aggregates in aqueous solutions, which partially decompose upon the introduction of albumin into the solution. The hydrophilic squarylium dye with sulfonate groups can be recommended for tests as a spectral-fluorescent probe for serum albumins in extracellular media of living organisms.

  11. Tyrosine fluorescence probing of conformational changes in tryptophan-lacking domain of albumins

    NASA Astrophysics Data System (ADS)

    Zhdanova, N. G.; Maksimov, E. G.; Arutyunyan, A. M.; Fadeev, V. V.; Shirshin, E. A.

    2017-03-01

    We addressed the possibility of using tyrosine (Tyr) fluorescence for monitoring conformational changes of proteins which are undetectable via tryptophan (Trp) fluorescence. The model objects, human (HSA) and bovine (BSA) serum albumins, contain one and two Trp residues, respectively, while Tyr is more uniformly distributed over their structure. The results of the investigation of albumins interaction with ethanol using intrinsic Trp and Tyr steady-state and time-resolved picosecond fluorescence indicated the presence of an intermediate at 10% (v/v) of ethanol in solution, that was supported by the results of extrinsic fluorescence measurements with the Nile Red dye. Based on the comparison of HSA and BSA Trp and Tyr fluorescence, it was suggested that conformational changes at low ethanol concentration are located in the domain III of albumins, which lacks tryptophan residues. The sensitivity of Tyr fluorescence to domain III alterations was further verified by studying albumins interaction with GdnHCl.

  12. Tyrosine fluorescence probing of conformational changes in tryptophan-lacking domain of albumins.

    PubMed

    Zhdanova, N G; Maksimov, E G; Arutyunyan, A M; Fadeev, V V; Shirshin, E A

    2017-03-05

    We addressed the possibility of using tyrosine (Tyr) fluorescence for monitoring conformational changes of proteins which are undetectable via tryptophan (Trp) fluorescence. The model objects, human (HSA) and bovine (BSA) serum albumins, contain one and two Trp residues, respectively, while Tyr is more uniformly distributed over their structure. The results of the investigation of albumins interaction with ethanol using intrinsic Trp and Tyr steady-state and time-resolved picosecond fluorescence indicated the presence of an intermediate at 10% (v/v) of ethanol in solution, that was supported by the results of extrinsic fluorescence measurements with the Nile Red dye. Based on the comparison of HSA and BSA Trp and Tyr fluorescence, it was suggested that conformational changes at low ethanol concentration are located in the domain III of albumins, which lacks tryptophan residues. The sensitivity of Tyr fluorescence to domain III alterations was further verified by studying albumins interaction with GdnHCl.

  13. Adsorption of small biological molecules on silica from diluted aqueous solutions: Quantitative characterization and implications to the Bernal's hypothesis

    NASA Astrophysics Data System (ADS)

    Basiuk, Vladimir A.; Gromovoy, Taras Yu.; Khil'Chevskaya, Elena G.

    1995-08-01

    To describe quantitatively the adsorption of prebiotically important compounds of low molecular weight (amino acids, short linear peptides, cyclic dipeptides, the Krebs's cycle and other carboxylic acids, nucleosides and related phosphates) on silica surface from diluted neutral aqueous solutions, equilibrium constants (K) and free energies (-ΔG) of adsorption were determined from the retention values measured by means of high-performance liquid chromatography on a silica gel column and from the isotherms measured under static conditions. For most carboxylic acids (including amino acids and linear peptides) -ΔG values were negative and K<1, thus showing very weak adsorption. Cyclic dipeptides (2,5-piperazinediones) exhibited higher adsorbability; -ΔG>0 and K>1 were found for most of them. Influence of the structure of α-substituent on the adsorbability is analyzed. A linear dependence of -ΔG on the number of aliphatic carbon atoms in a sorbate molecule was found for the series of aliphatic bifunctional amino acids, related dipeptides and 2,5-piperazinediones, as well as for the row from glycine to triglycyl glycine. The adsorption of nucleosides and their phosphates is characterized by much higherK and -ΔG values (of the order of 102 and 104, respectively). The adsorption data available from our work and literature are summarized and discussed with implications to the Bernal's hypothesis on the roles of solid surfaces in the prebiotic formation of biopolymers from monomeric ‘building blocks’.

  14. Comparison between protein repulsions by diblock PLA-PEO and albumin nanocoatings using OWLS.

    PubMed

    Leclercq, Laurent; Vert, Michel

    2017-02-01

    A previous investigation suggested that a surface bearing a rinsing-resistant depot (nanocoating) of albumin is more protein-repulsive than the same surface physically pegylated by a poly(D,L-lactic acid)-poly(ethylene oxide) diblock copolymer. To complement the study, Optical Waveguide Lightmode Spectroscopy was used to compare the mass and the thickness of protein depots from different systems, namely albumin alone at different concentrations, a mixture of albumin + fibrinogen + γ-globulin at their physiological concentrations, and sheep serum. The same standard OWLS protocol was applied to compare data for bare sensor chips, for chips covered by an albumin nanocoating, and for chips physically pegylated using poly(D,L-lactic acid)-poly(ethylene oxide) diblock copolymers with different compositions and block lengths. The strategy and the conditions being rather different from those generally used to study pegylation-related antifouling properties; the literature was first reviewed critically. Then full coverage of sensor chips by albumin was demonstrated. The comparative study confirmed that albumin was more protein-repulsive than any of the diblock copolymers, irrespective of the protein system. Furthermore, it was found that pegylated surfaces were albumin-repulsive only when the concentration of the protein solution flowing over the surface was very low (0.1 g/L). It was not possible to correlate the copolymer data to PEO chain density, chain length and existence of brush. The in vitro repulsive activity of albumin was not affected by drying and rehydration, a feature of interest for storage of albumin-coated surfaces. All these observations confirmed our preliminary findings and showed that considering model proteins individually or in mixtures at concentrations far from physiological concentrations are not suitable to reflect the reality of full blood-surface interactions.

  15. Is albumin administration in the acutely ill associated with increased mortality? Results of the SOAP study

    PubMed Central

    Vincent, Jean-Louis; Sakr, Yasser; Reinhart, Konrad; Sprung, Charles L; Gerlach, Herwig; Ranieri, V Marco

    2005-01-01

    Introduction Albumin administration in the critically ill has been the subject of some controversy. We investigated the use of albumin solutions in European intensive care units (ICUs) and its relationship to outcome. Methods In a cohort, multicenter, observational study, all patients admitted to one of the participating ICUs between 1 May and 15 May 2002 were followed up until death, hospital discharge, or for 60 days. Patients were classified according to whether or not they received albumin at any time during their ICU stay. Results Of 3,147 admitted patients, 354 (11.2%) received albumin and 2,793 (88.8%) did not. Patients who received albumin were more likely to have cancer or liver cirrhosis, to be surgical admissions, and to have sepsis. They had a longer length of ICU stay and a higher mortality rate, but were also more severely ill, as manifested by higher simplified acute physiology score (SAPS) II and sequential organ failure assessment (SOFA) scores than the other patients. A Cox proportional hazard model indicated that albumin administration was significantly associated with decreased 30-day survival. Moreover, in 339 pairs matched according to a propensity score, ICU and hospital mortality rates were higher in the patients who had received albumin than in those who had not (34.8 versus 20.9% and 41.3 versus 27.7%, respectively, both p < 0.001). Conclusion Albumin administration was associated with decreased survival in this population of acutely ill patients. Further prospective randomized controlled trials are needed to examine the effects of albumin administration in sub-groups of acutely ill patients. PMID:16356223

  16. Total Protein and Albumin/Globulin Ratio Test

    MedlinePlus

    ... Policy | Opportunities Total Protein and Albumin/Globulin (A/G) Ratio Share this page: Was this page helpful? Also known as: TP; Albumin/Globulin Ratio; A/G Ratio Formal name: Total Protein; Albumin to Globulin ...

  17. Cubilin is an albumin binding protein important for renal tubular albumin reabsorption.

    PubMed

    Birn, H; Fyfe, J C; Jacobsen, C; Mounier, F; Verroust, P J; Orskov, H; Willnow, T E; Moestrup, S K; Christensen, E I

    2000-05-01

    Using affinity chromatography and surface plasmon resonance analysis, we have identified cubilin, a 460-kDa receptor heavily expressed in kidney proximal tubule epithelial cells, as an albumin binding protein. Dogs with a functional defect in cubilin excrete large amounts of albumin in combination with virtually abolished proximal tubule reabsorption, showing the critical role for cubilin in the uptake of albumin by the proximal tubule. Also, by immunoblotting and immunocytochemistry we show that previously identified low-molecular-weight renal albumin binding proteins are fragments of cubilin. In addition, we find that mice lacking the endocytic receptor megalin show altered urinary excretion, and reduced tubular reabsorption, of albumin. Because cubilin has been shown to colocalize and interact with megalin, we propose a mechanism of albumin reabsorption mediated by both of these proteins. This process may prove important for understanding interstitial renal inflammation and fibrosis caused by proximal tubule uptake of an increased load of filtered albumin.

  18. Human serum albumin crystals and method of preparation

    NASA Technical Reports Server (NTRS)

    Carter, Daniel C. (Inventor)

    1989-01-01

    Human serum albumin (HSA) crystals are provided in the form of tetragonal plates having the space groups P42(sub 1)2, the crystals being grown to sizes in excess of 0.5 mm in two dimensions and a thickness of 0.1 mm. Growth of the crystals is carried out by a hanging drop method wherein a precipitant solution containing polyethylene glycol (PEG) and a phosphate buffer is mixed with an HSA solution, and a droplet of mixed solution is suspended over a well of precipitant solution. Crystals grow to the desired size in 3 to 7 days. Concentration of reagents, pH and other parameters are controlled within prescribed limits. The resulting crystals exhibit a size and quality such as to allow performance of x ray diffraction studies and enable the conduct of drug binding studies as well as genetic engineering studies.

  19. Resveratrol binding to human serum albumin.

    PubMed

    N' soukpoe-Kossi, C N; St-Louis, C; Beauregard, M; Subirade, M; Carpentier, R; Hotchandani, S; Tajmir-Riahi, H A

    2006-12-01

    Resveratrol (Res), a polyphenolic compound found largely in the skin of red grape and wine, exhibits a wide range of pharmaceutical properties and plays a role in prevention of human cardiovascular diseases [Pendurthi et al., Arterioscler. Thromb. Vasc. Biol. 19, 419-426 (1999)]. It shows a strong affinity towards protein binding and used as inhibitor for cyclooxygenase and ribonuclease reductase. The aim of this study was to examine the interaction of resveratrol with human serum albumin (HSA) in aqueous solution at physiological conditions, using a constant protein concentration (0.3 mM) and various pigment contents (microM to mM). FTIR, UV-Visible, CD, and fluorescence spectroscopic methods were used to determine the resveratrol binding mode, the binding constant and the effects of pigment complexation on protein secondary structure. Structural analysis showed that resveratrol bind non-specifically (H-bonding) via polypeptide polar groups with overall binding constant of K(Res) = 2.56 x 10(5) M(-1). The protein secondary structure, analysed by CD spectroscopy, showed no major alterations at low resveratrol concentrations (0.125 mM), whereas at high pigment content (1 mM), major increase of alpha-helix from 57% (free HSA) to 62% and a decrease of beta-sheet from 10% (free HSA) to 7% occurred in the resveratrol-HSA complexes. The results indicate a partial stabilization of protein secondary structure at high resveratrol content.

  20. Review: Glycation of human serum albumin

    PubMed Central

    Anguizola, Jeanethe; Matsuda, Ryan; Barnaby, Omar S.; Joseph, K.S.; Wa, Chunling; DeBolt, Erin; Koke, Michelle; Hage, David S.

    2013-01-01

    Glycation involves the non-enzymatic addition of reducing sugars and/or their reactive degradation products to amine groups on proteins. This process is promoted by the presence of elevated blood glucose concentrations in diabetes and occurs with various proteins that include human serum albumin (HSA). This review examines work that has been conducted in the study and analysis of glycated HSA. The general structure and properties of HSA are discussed, along with the reactions that can lead to modification of this protein during glycation. The use of glycated HSA as a short-to-intermediate term marker for glycemic control in diabetes is examined, and approaches that have been utilized for measuring glycated HSA are summarized. Structural studies of glycated HSA are reviewed, as acquired for both in vivo and in vitro glycated HSA, along with data that have been obtained on the rate and thermodynamics of HSA glycation. In addition, this review considers various studies that have investigated the effects of glycation on the binding of HSA with drugs, fatty acids and other solutes and the potential clinical significance of these effects. PMID:23891854

  1. Protease Inhibition by Oleic Acid Transfer From Chronic Wound Dressings to Albumin

    SciTech Connect

    Edwards, J. V.; Howley, Phyllis; Davis, Rachel M.; Mashchak, Andrew D.; Goheen, Steven C.

    2007-08-01

    High elastase and cathepsin G activities have been observed in chronic wounds. These levels can inhibit healing through degradation of growth factors, cytokines, and extracellular matrix proteins. Oleic acid (18:1) is a non-toxic elastase inhibitor with some potential for redressing the imbalance of elastase activity found in chronic wounds. Cotton wound dressing material was characterized as a transfer carrier for affinity uptake of 18:1 by albumin under conditions mimicking chronic wounds. 18:1-treated cotton was examined for its ability to bind and release the fatty acid in the presence of albumin. The mechanism of 18:1 uptake from cotton and binding by albumin was examined with both intact dressings and cotton fiber-designed chromatography. Raman spectra of the albumin-18:1 complexes under liquid-liquid equilibrium conditions revealed fully saturated albumin-18:1 complexes with a 1:1 weight ratio of albumin:18:1. Cotton chromatography under liquid-solid equilibrium conditions revealed oleic acid transfer from cotton to albumin at 27 mole equivalents of 18:1 per mole albumin. Cotton was contrasted with hydrogel, and hydrocolloid wound dressing for its comparative ability to lower elastase activity. Each dressing material evaluated was found to release 18:1 in the presence of albumin with significant inhibition of elastase activity. The 18:1-formulated wound dressings lowered elastase activity in a dose dependent manner in the order cotton gauze > hydrogel > hydrocolloid. In contrast the cationic serine protease Cathepsin G was inihibited by 18:1 within a narrow range of 18:1-cotton formulations. Four per cent Albumin solutions were most effective in binding cotton bound-18:1. However, 2% albumin was sufficient to transfer quantities of 18:1 necessary to achieve a significant elastase-lowering effect. Formulations with 128 mg 18:1/g cotton gauze had equivalent elastase lowering with 1 - 4% albumin. 18:1 bound to cotton wound dressings may have promise in the

  2. Albumin for end-stage liver disease.

    PubMed

    Lee, June Sung

    2012-03-01

    Albumin has been widely used in patients with cirrhosis in an attempt to improve circulatory and renal functions. The benefits of albumin infusions in preventing the deterioration in renal function associated with large-volume paracentesis, spontaneous bacterial peritonitis, and established hepatorenal syndrome in conjunction with a vasoconstrictor are well established. While some of these indications are supported by the results of randomized studies, others are based only on clinical experience and have not been proved in prospective studies. The paucity of well-designed trials, the high cost of albumin, the lack of a clear-cut survival benefit, and fear of transmitting unknown infections make the use of albumin controversial. The recent development of the molecular adsorbent recirculating system, an albumin dialysis, is an example of the capacity of albumin to act by mechanisms other than its oncotic effect. Efforts should be made to define the indications for albumin use, the dose required, and predictors of response, so that patients gain the maximum benefit from its administration.

  3. Multiple fatty acid binding to albumin in human blood plasma.

    PubMed

    Brodersen, R; Andersen, S; Vorum, H; Nielsen, S U; Pedersen, A O

    1990-04-30

    Binding equilibria of long-chain fatty acids to human serum albumin, in serum or plasma, were studied by a dialysis exchange rate technique. Palmitate was added to citrated plasma in vitro and it was observed that between six and ten palmitate molecules were bound to albumin with nearly equal affinity. Observations in vivo gave similar results in the following series: (a) in two volunteers with increased fatty acid concentrations after fasting, exercise, and a cold shower: (b) in three male volunteers in whom high concentrations of non-esterified fatty acids, up to 4.6 mM, were induced by intravenous administration of a preparation of lecithin/glycocholate mixed micelles, and (c) in 81 patients with diabetes mellitus, type I. The binding pattern of palmitate in serum or plasma is essentially different from that observed with palmitate added to buffered solutions of pure albumin when two molecules are tightly bound and about four additional molecules with lower affinity. The differences may partly be explained by the presence of chloride ions in blood plasma, reducing the affinity for binding of the first two fatty acid molecules, and partly by facilitated binding of several molecules of mixed fatty acids, as found in plasma.

  4. Investigation of Bovine Serum Albumin (BSA) Attachment onto Self-Assembled Monolayers (SAMs) Using Combinatorial Quartz Crystal Microbalance with Dissipation (QCM-D) and Spectroscopic Ellipsometry (SE).

    PubMed

    Phan, Hanh T M; Bartelt-Hunt, Shannon; Rodenhausen, Keith B; Schubert, Mathias; Bartz, Jason C

    2015-01-01

    Understanding protein adsorption kinetics to surfaces is of importance for various environmental and biomedical applications. Adsorption of bovine serum albumin to various self-assembled monolayer surfaces including neutral and charged hydrophilic and hydrophobic surfaces was investigated using in-situ combinatorial quartz crystal microbalance with dissipation and spectroscopic ellipsometry. Adsorption of bovine serum albumin varied as a function of surface properties, bovine serum albumin concentration and pH value. Charged surfaces exhibited a greater quantity of bovine serum albumin adsorption, a larger bovine serum albumin layer thickness, and increased density of bovine serum albumin protein compared to neutral surfaces at neutral pH value. The quantity of adsorbed bovine serum albumin protein increased with increasing bovine serum albumin concentration. After equilibrium sorption was reached at pH 7.0, desorption of bovine serum albumin occurred when pH was lowered to 2.0, which is below the isoelectric point of bovine serum albumin. Our data provide further evidence that combinatorial quartz crystal microbalance with dissipation and spectroscopic ellipsometry is a sensitive analytical tool to evaluate attachment and detachment of adsorbed proteins in systems with environmental implications.

  5. Investigation of Bovine Serum Albumin (BSA) Attachment onto Self-Assembled Monolayers (SAMs) Using Combinatorial Quartz Crystal Microbalance with Dissipation (QCM-D) and Spectroscopic Ellipsometry (SE)

    PubMed Central

    Phan, Hanh T. M.; Bartelt-Hunt, Shannon; Rodenhausen, Keith B.; Schubert, Mathias; Bartz, Jason C.

    2015-01-01

    Understanding protein adsorption kinetics to surfaces is of importance for various environmental and biomedical applications. Adsorption of bovine serum albumin to various self-assembled monolayer surfaces including neutral and charged hydrophilic and hydrophobic surfaces was investigated using in-situ combinatorial quartz crystal microbalance with dissipation and spectroscopic ellipsometry. Adsorption of bovine serum albumin varied as a function of surface properties, bovine serum albumin concentration and pH value. Charged surfaces exhibited a greater quantity of bovine serum albumin adsorption, a larger bovine serum albumin layer thickness, and increased density of bovine serum albumin protein compared to neutral surfaces at neutral pH value. The quantity of adsorbed bovine serum albumin protein increased with increasing bovine serum albumin concentration. After equilibrium sorption was reached at pH 7.0, desorption of bovine serum albumin occurred when pH was lowered to 2.0, which is below the isoelectric point of bovine serum albumin. Our data provide further evidence that combinatorial quartz crystal microbalance with dissipation and spectroscopic ellipsometry is a sensitive analytical tool to evaluate attachment and detachment of adsorbed proteins in systems with environmental implications. PMID:26505481

  6. In vitro inhibition of human neutrophil elastase by oleic acid albumin formulations from derivatized cotton wound dressings.

    PubMed

    Edwards, J Vincent; Howley, Phyllis; Cohen, I Kelman

    2004-10-13

    Human neutrophil elastase (HNE) is elevated in chronic wounds. Oleic acid albumin formulations that inhibit HNE may be applicable to treatment modalities for chronic wounds. Oleic acid/albumin formulations with mole ratios of 100:1, 50:1, and 25:1 (oleic acid to albumin) were prepared and found to have dose response inhibition properties against HNE. The IC50 values for inhibition of HNE with oleic acid/albumin formulations were 0.029-0.049 microM. Oleic acid/albumin (BSA) formulations were bound to positively and negatively charged cotton wound dressings and assessed for elastase inhibition using a fiber bound formulation in an assay designed to mimic HNE inhibition in the wound. Cotton derivatized with both carboxylate and amine functional groups were combined with oleic acid/albumin formulations at a maximum loading of 0.030 mg oleic acid + 0.14 mg BSA/mg fiber. The IC50 values for inhibition of HNE with oleic acid/albumin formulations bound to derivatized cotton were 0.26-0.42 microM. Release of the oleic acid/albumin formulation from the fiber was measured by measuring oleic acid levels with quantitative GC analysis. Approximately, 35-50% of the fiber bound formulation was released into solution within the first 15 min of incubation. Albumin was found to enhance the rate of elastase hydrolysis of the substrate within a concentration range of 0.3-50 g/L. The acceleration of HNE substrate hydrolysis by albumin required increased concentration of inhibitor in the formulation to obtain complete inhibition of HNE. Oleic acid formulations prepared with albumin enable transport, solubility and promote dose response inhibition of HNE from derivatized cotton fibers under aqueous conditions mimicking the chronic wound.

  7. Asymmetric ( UC)albumin transport across bullfrog alveolar epithelium

    SciTech Connect

    Kim, K.J.; LeBon, T.R.; Shinbane, J.S.; Crandall, E.D.

    1985-10-01

    Bullfrog lungs were prepared as planar sheets and bathed with Ringer solution in Ussing chambers. In the presence of a constant electrical gradient (20, 0, or -20 mV) across the tissue, UC-labeled bovine serum albumin or inulin was instilled into the upstream reservoir and the rate of appearance of the tracer in the downstream reservoir was monitored. Two lungs from the same animal were used to determine any directional difference in tracer fluxes. An apparent permeability coefficient was estimated from a relationship between normalized downstream radioactivities and time. Results showed that the apparent permeability of albumin in the alveolar to pleural direction across the alveolar epithelial barrier is 2.3 X 10(-7) cm/s, significantly greater (P less than 0.0005) than that in the pleural to alveolar direction (5.3 X 10(-8) cm/s) when the tissue was short circuited. Permeability of inulin, on the other hand, did not show any directional dependence and averaged 3.1 X 10(-8) cm/s in both directions. There was no effect on radiotracer fluxes permeabilities of different electrical gradients across the tissue. Gel electrophoretograms and corresponding radiochromatograms suggest that the large and asymmetric isotope fluxes are not primarily due to digestion or degradation of labeled molecules. Inulin appears to traverse the alveolar epithelial barrier by simple diffusion through hydrated paracellular pathways. On the other hand, ( UC)albumin crosses the alveolar epithelium more rapidly than would be expected by simple diffusion. These asymmetric and large tracer fluxes suggest that a specialized mechanism is present in alveolar epithelium that may be capable of helping to remove albumin from the alveolar space.

  8. Surface tension in situ in flooded alveolus unaltered by albumin.

    PubMed

    Kharge, Angana Banerjee; Wu, You; Perlman, Carrie E

    2014-09-01

    In the acute respiratory distress syndrome, plasma proteins in alveolar edema liquid are thought to inactivate lung surfactant and raise surface tension, T. However, plasma protein-surfactant interaction has been assessed only in vitro, during unphysiologically large surface area compression (%ΔA). Here, we investigate whether plasma proteins raise T in situ in the isolated rat lung under physiologic conditions. We flood alveoli with liquid that omits/includes plasma proteins. We ventilate the lung between transpulmonary pressures of 5 and 15 cmH2O to apply a near-maximal physiologic %ΔA, comparable to that of severe mechanical ventilation, or between 1 and 30 cmH2O, to apply a supraphysiologic %ΔA. We pause ventilation for 20 min and determine T at the meniscus that is present at the flooded alveolar mouth. We determine alveolar air pressure at the trachea, alveolar liquid phase pressure by servo-nulling pressure measurement, and meniscus radius by confocal microscopy, and we calculate T according to the Laplace relation. Over 60 ventilation cycles, application of maximal physiologic %ΔA to alveoli flooded with 4.6% albumin solution does not alter T; supraphysiologic %ΔA raise T, transiently, by 51 ± 4%. In separate experiments, we find that addition of exogenous surfactant to the alveolar liquid can, with two cycles of maximal physiologic %ΔA, reduce T by 29 ± 11% despite the presence of albumin. We interpret that supraphysiologic %ΔA likely collapses the interfacial surfactant monolayer, allowing albumin to raise T. With maximal physiologic %ΔA, the monolayer likely remains intact such that albumin, blocked from the interface, cannot interfere with native or exogenous surfactant activity. Copyright © 2014 the American Physiological Society.

  9. Fusion to a highly stable consensus albumin binding domain allows for tunable pharmacokinetics.

    PubMed

    Jacobs, Steven A; Gibbs, Alan C; Conk, Michelle; Yi, Fang; Maguire, Diane; Kane, Colleen; O'Neil, Karyn T

    2015-10-01

    A number of classes of proteins have been engineered for high stability using consensus sequence design methods. Here we describe the engineering of a novel albumin binding domain (ABD) three-helix bundle protein. The resulting engineered ABD molecule, called ABDCon, is expressed at high levels in the soluble fraction of Escherichia coli and is highly stable, with a melting temperature of 81.5°C. ABDCon binds human, monkey and mouse serum albumins with affinity as high as 61 pM. The solution structure of ABDCon is consistent with the three-helix bundle design and epitope mapping studies enabled a precise definition of the albumin binding interface. Fusion of a 10 kDa scaffold protein to ABDCon results in a long terminal half-life of 60 h in mice and 182 h in cynomolgus monkeys. To explore the link between albumin affinity and in vivo exposure, mutations were designed at the albumin binding interface of ABDCon yielding variants that span an 11 000-fold range in affinity. The PK properties of five such variants were determined in mice in order to demonstrate the tunable nature of serum half-life, exposure and clearance with variations in albumin binding affinity.

  10. Three-dimensional structure of human serum albumin

    NASA Technical Reports Server (NTRS)

    Carter, Daniel C.; He, Xiao-Min; Munson, Sibyl H.; Twigg, Pamela D.; Gernert, Kim M.; Broom, M. Beth; Miller, Teresa Y.

    1989-01-01

    The three-dimensional structure of human serum albumin has been solved at 6.0 A resolution by the method of multiple isomorphous replacement. Crystals were grown from solutions of polyethylene glycol in the infrequently observed space group P42(1)2 and diffracted X-rays to lattice d-spacings of less than 2.9 A. The electron density maps are of high quality and revealed the structure as a predominantly alpha-helical globin protein in which the course of the polypeptide can be traced. The binding loci of several organic compounds have been determined.

  11. [Modified albumin in harp seal blood serum].

    PubMed

    Erokhina, I A

    1999-01-01

    The content of modified albumin (Am) in harp seal (Pagophilus groenlandica Erxleben, 1777) blood serum was studied. Am was determined by paper electrophoresis by means of re-precipitation in the trichloroacetic acid-ethanol system. Modified albumin content in normal seal pups' blood serum increased from 1990 to 1994. The Am level in undernourished pups was stable from year to year and higher than in normal pups. In oceanarium investigations it was revealed a low albumin resistance to denaturation and the dependence of Am content on the animals' physiological state. Thus there is a possibility to regard modified albumin content as one of the significant parameters in biomonitoring of harp seal population and, moreover, as a supplementary criterion for estimation of seals' health state in captivity.

  12. Paclitaxel Albumin-stabilized Nanoparticle Formulation

    Cancer.gov

    This page contains brief information about paclitaxel albumin-stabilized nanoparticle formulation and a collection of links to more information about the use of this drug, research results, and ongoing clinical trials.

  13. Albumin-stabilized fluorescent silver nanodots

    NASA Astrophysics Data System (ADS)

    Sych, Tomash; Polyanichko, Alexander; Kononov, Alexei

    2017-07-01

    Ligand-stabilized Ag nanoclusters (NCs) possess many attractive features including high fluorescence quantum yield, large absorption cross-section, good photostability, large Stokes shift and two-photon absorption cross sections. While plenty of fluorescent clusters have been synthesized on various polymer templates, only a few studies have been reported on the fluorescent Ag clusters on peptides and proteins. We study silver NCs synthesized on different protein matrices, including bovine serum albumin, human serum albumin, egg albumin, equine serum albumin, and lysozyme. Our results show that red-emitting Ag NCs can effectively be stabilized by the disulfide bonds in proteins and that the looser structure of the denatured protein favors formation of the clusters.

  14. Albumin treatment reduces neurological deficit and protects blood-brain barrier integrity after acute intracortical hematoma in the rat.

    PubMed

    Belayev, Ludmila; Saul, Isabel; Busto, Raul; Danielyan, Kristine; Vigdorchik, Alexey; Khoutorova, Larissa; Ginsberg, Myron D

    2005-02-01

    Acute intracerebral hemorrhage (ICH) is a common and severe form of stroke. To date, medical management of ICH has had scant impact on morbidity and mortality. Because albumin therapy is markedly neuroprotective in preclinical models of ischemic stroke, and because ischemic and hemorrhagic stroke share several common injury mechanisms, we hypothesized that albumin therapy might also benefit ICH. Acute intracortical hematoma was produced in anesthetized, normothermic rats by the single stereotaxic injection of 50 muL of autologous, nonheparinized whole blood over 5 minutes. Separate animal groups were treated either with 25% human albumin, 1.25 g/kg, or with intravenous saline vehicle at 60 minutes after ICH. Neurobehavior was quantified sequentially over the next 2 to 7 days. Damage to the blood-brain barrier was assessed at 2 days after ICH by fluorometric measurement of Evans blue extravasation in dissected brain regions. High-grade neurological deficits were present in all rats at 50 minutes after ICH (score 10.3+/-0.2, mean+/-SEM [maximal score 12]). Albumin-treated rats showed improved neuroscores relative to saline-treated animals beginning within hours of treatment and persisting throughout the 7-day survival period. At 3 and 7 days, mean total neuroscores of the albumin group were 38% to 43% lower than in saline-treated animals. Perihematomal Evans blue discoloration was readily evident in saline-treated ICH rats but was reduced by albumin treatment. Hemispheric Evans blue content ipsilateral to the hematoma was reduced by 49% by albumin treatment (albumin 93.9+/-13.3 versus saline 184.7+/-33.7 mg/g, P<0.05). Hematoma volume and brain swelling were not affected by albumin treatment. Prompt albumin therapy improves neurological function and blood-brain barrier integrity after acute intracortical hematoma. These observations have important potential clinical implications.

  15. Bisalbuminemia. A new molecular variant, albumin Vancouver.

    PubMed

    Frohlich, J; Kozier, J; Campbell, D J; Curnow, J V; Tárnoky, A L

    1978-11-01

    Of 18 members of a Fiji Indian family investigated, eight of the 12 males and two of the six females had an electrophoretically slow-type bisalbuminemia (alloalbuminemia). The albumin was characterized by the hiterto unique ratio of the two bands (Al A 35%: variant 65%), and by dye-binding studies and electrophoretic mobility in different media. The data suggest that this is a new variant, which we propose to call albumin Vancouver (Al Va).

  16. Albumin nanostructures as advanced drug delivery systems.

    PubMed

    Karimi, Mahdi; Bahrami, Sajad; Ravari, Soodeh Baghaee; Zangabad, Parham Sahandi; Mirshekari, Hamed; Bozorgomid, Mahnaz; Shahreza, Somayeh; Sori, Masume; Hamblin, Michael R

    2016-11-01

    One of the biggest impacts that the nanotechnology has made on medicine and biology, has been in the area of drug delivery systems (DDSs). Many drugs suffer from serious problems concerning insolubility, instability in biological environments, poor uptake into cells and tissues, sub-optimal selectivity for targets and unwanted side effects. Nanocarriers can be designed as DDSs to overcome many of these drawbacks. One of the most versatile building blocks to prepare these nanocarriers is the ubiquitous, readily available and inexpensive protein, serum albumin. Areas covered: This review covers the use of different types of albumin (human, bovine, rat, and chicken egg) to prepare nanoparticle and microparticle-based structures to bind drugs. Various methods have been used to modify the albumin structure. A range of targeting ligands can be attached to the albumin that can be recognized by specific cell receptors that are expressed on target cells or tissues. Expert opinion: The particular advantages of albumin used in DDSs include ready availability, ease of chemical modification, good biocompatibility, and low immunogenicity. The regulatory approvals that have been received for several albumin-based therapeutic agents suggest that this approach will continue to be successfully explored.

  17. Portal copper transport in rats by albumin

    SciTech Connect

    Gordon, D.T.; Leinart, A.S.; Cousins, R.J.

    1987-03-01

    The distribution of newly absorbed copper among serum proteins obtained from the portal circulation of rats was examined by conventional and high-performance gel filtration chromatography, affinity chromatography, and Western blotting. Within 10-30 min after being administered by gavage or directly into the intestine, /sup 67/Cu and /sup 64/Cu, respectively, were recovered in the albumin fraction. By 8 h after administration of the radionuclides, virtually all of the radioactivity was found with ceruloplasmin. Affigel blue fractionation and subsequent Superose-6 chromatography further demonstrated that all of the copper in the albumin-containing fractions was in fact bound to this protein rather than high molecular weight moieties. Vascular perfusion of the isolated rat intestine, where /sup 64/Cu was infused into the lumen, showed that newly absorbed /sup 64/Cu in the vascular perfusate collected from the cannulated portal vein was associated with albumin. Uptake of radioactivity by isolated rat liver parenchymal cells from medium containing rat serum with /sup 67/Cu bound to albumin was demonstrated. In vitro binding of /sup 64/Cu to serum proteins that were transferred to nitrocellulose by Western blotting techniques showed that albumin is essentially the only protein that binds appreciable amounts of copper. The data suggest that albumin is the plasma protein that is responsible for the initial transport of copper after absorption.

  18. Lungfish albumin is more similar to tetrapod than to teleost albumins: purification and characterisation of albumin from the Australian lungfish, Neoceratodus forsteri.

    PubMed

    Metcalf, Victoria J; George, Peter M; Brennan, Stephen O

    2007-07-01

    Lobe-finned fish, particularly lungfish, are thought of as the closest extant relatives to tetrapods. Albumin, the major vertebrate plasma protein, has been well studied in tetrapods, but there exists no comparative study of the presence and characteristics of albumin in lobe-finned fish versus other vertebrates. There is a controversy over the presence of albumin in fish, although it is present in salmonids and lamprey. The presence of albumin in lungfish has also recently been documented. We identified albumin in plasma of the Australian lungfish, Neoceratodus forsteri, using a combination of agarose gel electrophoresis, [(14)C]palmitic acid binding and SDS-PAGE. Lungfish albumin was purified using DEAE-ion exchange chromatography, and has a mass of 67 kDa, is present at approximately 8 g/L in plasma and like other fish albumins, does not bind nickel. However, like tetrapod albumins, it is not glycosylated. N-terminal and internal peptide sequencing generated 101 amino acids of sequence, which showed a high degree of identity with tetrapod albumins. Despite the similarity in sequence but congruent with the evolutionary distances separating them, lungfish albumin did not cross-react with anti-chicken or anti-tuatara A albumin antisera. Lungfish albumin has characteristics more akin with tetrapod albumin and less like those of other fish.

  19. Expulsion of bovine serum albumin from the air/water interface by a sparingly soluble lecithin lipid.

    PubMed

    Phang, Tze-Lee; Franses, Elias I

    2004-07-15

    Dynamic surface tensiometry, ellipsometry, and infrared reflection-absorption spectroscopy (IRRAS) were used to study the dynamic adsorption and surface tensions of dilauroylphosphatidylcholine (DLPC) in the presence of bovine serum albumin (BSA). Results show that the equilibrium adsorbed layers consist mostly of DLPC, which can produce dynamic surface tensions (1 mN/m) as low as the more successful lung surfactant replacement formulations. When the aqueous surface expands and contracts sinusoidally, BSA can coadsorb and lead to slightly higher dynamic surface tensions than when DLPC is alone. Similar results were obtained with BSA and sodium myristate [McClellan and Franses, Colloids Surf. B 30 (2003) 1]. Expulsion of the BSA in the layer by DLPC can take from 5 to 15 min, depending on relative concentrations and history of solute addition. This is shown by tensiometry measurements on mixtures, and also by injecting aqueous DLPC underneath adsorbed BSA layers and probing the surface layer with ellipsometry and IRRAS. Albumin layers from buffer solutions aged up to 30 h can be expelled by DLPC. In pure water, there is an initial enhancement in protein adsorption after the DLPC is injected. This can be explained by the hypothesis that DLPC molecules bind with BSA molecules to form a hydrophobic lipoprotein complex, which is more hydrophobic than the protein itself. Since DLPC produces lower surface energy than BSA and--being slightly soluble--adsorbs to the surface by a molecular mechanism, it fulfills the thermodynamic and dynamic requirements for expelling the BSA from the surface. The results have implications for minimizing lung surfactant inhibition by serum proteins, as it occurs in the cases of adult or acute respiratory distress syndrome.

  20. Polyamine analogues bind human serum albumin.

    PubMed

    Beauchemin, R; N'soukpoé-Kossi, C N; Thomas, T J; Thomas, T; Carpentier, R; Tajmir-Riahi, H A

    2007-10-01

    Polyamine analogues show antitumor activity in experimental models, and their ability to alter activity of cytotoxic chemotherapeutic agents in breast cancer is well documented. Association of polyamines with nucleic acids and protein is included in their mechanism of action. The aim of this study was to examine the interaction of human serum albumin (HSA) with several polyamine analogues, such as 1,11-diamino-4,8-diazaundecane (333), 3,7,11,15-tetrazaheptadecane.4HCl (BE-333), and 3,7,11,15,19-pentazahenicosane.5HCl (BE-3333), in aqueous solution at physiological conditions using a constant protein concentration and various polyamine contents (microM to mM). FTIR, UV-visible, and CD spectroscopic methods were used to determine the polyamine binding mode and the effects of polyamine complexation on protein stability and secondary structure. Structural analysis showed that polyamines bind nonspecifically (H-bonding) via polypeptide polar groups with binding constants of K333 = 9.30 x 10(3) M(-1), KBE-333 = 5.63 x 10(2) M(-1), and KBE-3333 = 3.66 x 10(2) M(-1). The protein secondary structure showed major alterations with a reduction of alpha-helix from 55% (free protein) to 43-50% and an increase of beta-sheet from 17% (free protein) to 29-36% in the 333, BE-333, and BE-3333 complexes, indicating partial protein unfolding upon polyamine interaction. HSA structure was less perturbed by polyamine analogues compared to those of the biogenic polyamines.

  1. Albumin-Like Proteins Are Critical Regulators of Vascular Redox Signaling

    PubMed Central

    Ramos, Kenneth S.; Stribinskis, Vilius; Steffen, Marlene C.; Nanez, Adrian; Montoya-Durango, Diego; He, Qiang

    2013-01-01

    This laboratory previously identified an albumin-like protein (denoted as p70) as a component of the macromolecular complex assembled within the 5′-regulatory region of redox-sensitive genes in vascular smooth muscle cells (vSMCs). Here we show that p70 is present in the cytosolic and nuclear compartments of vSMCs and dynamically responsive to redox status. Intense cytoplasmic and perinuclear staining, coupled with enhanced nuclear localization, was observed in vSMCs, but not HepG2 cells, treated with benzo(a)pyrene (BaP), H2O2, or N-acetylcysteine, agents known to modulate redox status. 3′ RACE indicated that p70 is not generated as a product of endogenous gene expression, but rather taken up from the extracellular compartment. While p70 was undetectable in cells grown for 24 hours under serum-free conditions, cell-associated, acid-resistant albumin was detected 30 min after the addition of exogenous albumin. vSMCs incubated at 4°C with 100 μg/mL unlabeled BSA and 10 μg/mL FITC-BSA for 60 minutes and switched to 37°C to examine temperature-sensitive label uptake showed punctate structures throughout the cell consistent with albumin internalization at the higher temperature. Albumin was found to influence redox-signaling, as evidenced by modulation of cyp1a1 gsta1 and Ha-ras gene inducibility. Together, these results implicate albumin and albumin-like proteins as critical regulators of vascular redox signaling. PMID:23476722

  2. A step toward simplified detection of serum albumin on SDS-PAGE using an environment-sensitive flavone sensor.

    PubMed

    Liu, Bin; Pang, Yi; Bouhenni, Rachida; Duah, Ernest; Paruchuri, Sailaja; McDonald, Lucas

    2015-07-14

    In this study, we report a series of novel flavone-based sensors that exhibit a superior fluorescence response when interacting with serum albumin in real serum samples and in acrylamide gels. The detection limit of probe 4 for serum albumin solution is 0.09 μg mL(-1), and the detectable volume for monkey serum reaches as low as 0.03 μL.

  3. A step toward simplified detection of serum albumin on SDS-PAGE using an environment-sensitive flavone sensor

    PubMed Central

    Liu, Bin; Bouhenni, Rachida; Duah, Ernest; Paruchuri, Sailaja; McDonald, Lucas

    2015-01-01

    In this study, we report a series of novel flavone-based sensors that exhibit superior fluorescence response when interacting with serum albumin in real serum samples and in acrylamide gel. The detection limit of probe 4 for serum albumin solution is 0.09 μg/mL, and the detectable volume for monkey serum reaches as low as 0.03 μL. PMID:26068596

  4. Cu(II) bis(thiosemicarbazone) radiopharmaceutical binding to serum albumin: further definition of species dependence and associated substituent effects.

    PubMed

    Basken, Nathan E; Green, Mark A

    2009-07-01

    The pyruvaldehyde bis(N(4)-methylthiosemicarbazonato)copper(II) (Cu-PTSM) and diacetyl bis(N(4)-methylthiosemicarbazonato)copper(II) (Cu-ATSM) radiopharmaceuticals exhibit strong, species-dependent binding to the IIA site of human serum albumin (HSA), while the related ethylglyoxal bis(thiosemicarbazonato)copper(II) (Cu-ETS) radiopharmaceutical appears to exhibit only nonspecific binding to HSA and animal serum albumins. To further probe the structural basis for the species dependence of this albumin binding interaction, we examined protein binding of these three radiopharmaceuticals in solutions of albumin and/or serum from a broader array of mammalian species (rat, sheep, donkey, rabbit, cow, pig, dog, baboon, mouse, cat and elephant). We also evaluated the albumin binding of several copper(II) bis(thiosemicarbazone) chelates offering more diverse substitution of the ligand backbone. Cu-PTSM and Cu-ATSM exhibit a strong interaction with HSA that is not apparent with the albumins of other species, while the binding of Cu-ETS to albumin is much less species dependent. The strong interaction of Cu-PTSM with HSA does not appear to simply correlate with variation, relative to the animal albumins, of a single amino acid lining HSA's IIA site. Those agents that selectively interact with HSA share the common feature of only methyl or hydrogen substitution at the carbon atoms of the diimine fragment of the ligand backbone. The interspecies variations in albumin binding of Cu-PTSM and Cu-ATSM are not simply explained by unique amino acid substitutions in the IIA binding pocket of the serum albumins. However, the specific affinity for this region of HSA is disrupted when substituents bulkier than a methyl group appear on the imine carbons of the copper bis(thiosemicarbazone) chelate.

  5. Modification of continuous venovenous hemodiafiltration with single-pass albumin dialysate allows for removal of serum bilirubin.

    PubMed

    Chawla, Lakhmir S; Georgescu, Florin; Abell, Bruce; Seneff, Michael G; Kimmel, Paul L

    2005-03-01

    A 53-year-old woman was admitted to the hospital with ischemic colitis and underwent a subtotal colectomy. She developed acute renal failure, severe hyperbilirubinemia, and intense pruritus resistant to medical treatment. Extracorporeal albumin dialysis using a Molecular Adsorbent Recirculating System (MARS; Gambro Co, Lund, Sweden) has been used to treat liver failure and reduce total serum bilirubin (SB) levels. A trial of extracorporeal albumin dialysis with continuous renal replacement therapy (RRT) was instituted to achieve net removal of SB. A 25% albumin solution was mixed with conventional dialysate to yield a dialysate concentration of 1.85% or 5.0% albumin. The patient underwent 2 continuous RRT sessions using extracorporeal albumin dialysis (1.85% and 5.0% albumin dialysate). Pretreatment and posttreatment SB levels were determined, and total bilirubin concentration (TB) also was measured in each of the collection bags during conventional and albumin dialysis. Pretreatment and posttreatment SB levels were 50.4 mg/dL (862 micromol/L) and 39.0 mg/dL (667 micromol/L) with 1.85% albumin dialysate and 47.1 mg/dL (805 micromol/L) and 39.7 mg/dL (679 micromol/L) with 5.0% albumin dialysate, respectively. The collected dialysate TB level was 0.3 mg/dL (5 micromol/L) during nonalbumin RRT and increased to 1.37 +/- 0.06 mg/dL (23 +/- 1 micromol/L) with 1.85% albumin dialysis. The collected dialysate fluid TB level was 0.3 mg/dL (5 micromol/L) during the nonalbumin RRT and increased to 1.38 +/- 0.15 mg/dL (24 +/- 3 micromol/L) during 5.0% albumin RRT. Single-pass albumin dialysis with continuous RRT cleared SB better than standard continuous RRT. Single-pass albumin dialysis with continuous RRT is feasible and may be a viable alternative in centers that do not have access to MARS therapy. This modality merits additional evaluation for its efficacy in clearing albumin-bound serum toxins.

  6. Bromophenol blue binding to mammalian albumins and displacement of albumin-bound bilirubin.

    PubMed

    Kim, B Boon; Abdul Kadir, H; Tayyab, S

    2008-10-15

    Interaction of bromophenol blue (BPB) with serum albumins from different mammalian species, namely, human (HSA), bovine (BSA), goat (GSA), sheep (SSA), rabbit (RbSA), porcine (PSA) and dog (DSA) was studied using absorption and absorption difference spectroscopy. BPB-albumin complexes showed significant differences in the spectral characteristics, i.e., extent of bathochromic shift and hypochromism relative to the spectral features of free BPB. Absorption difference spectra of these complexes also showed variations in the position of maxima and absorption difference (deltaAbs.) values. Absorption difference spectra of different bilirubin (BR)-albumin complexes showed a significant blue shift accompanied by decrease in deltaAbs. values in presence of BPB which were indicative of the displacement of bound BR from its binding site in BR-albumin complexes. These changes in the difference spectral characteristics of BR-albumin complexes were more marked at higher BPB concentration. However, the extent of these changes was different for different BR-albumin complexes. Taken together, all these results suggest that BPB partially shares BR binding site on albumin and different mammalian albumins show differences in the microenvironment of the BR/BPB binding site.

  7. Photolytic insertion of albumin on activated carbon modified with ozone.

    PubMed

    Peralta Muniz Moreira, Regina de Fátima; Humeres, Eduardo; Berger, Carolina; Isabel Fernández, M; Santaballa, J A; Canle, Moisés

    2017-09-01

    254nm photolyses of bovine serum albumin [BSA] in aqueous solutions, were carried out in the presence of activated carbons modified by reaction with ozone. The photolyses were monitored by fluorescence spectroscopy and UV spectrophotometry, and the products were characterized by elemental analysis, FTIR, TGA, total organic carbon analyses [TOC], and XPS. The ozonation reaction was carried out at room temperature with O3 under dry and wet conditions. The carbon characterization showed that the reaction increased the amount of epoxide and carbonyl groups on the carbon matrix. The activated carbon modified with dry O3 exhibited higher concentration of oxidized groups in its surface, smaller surface area and lower thermal stability. Characterization of the photolysis of ozonized carbons pointed to a small release of carbon organic groups during the reaction with elimination of epoxide groups and increase of carbonyl groups without change of thermal stability. Photolysis of BSA in aqueous solution occurred with fluorescence quenching due to changes of the local microenvironment and/or macromolecular conformational changes. Absorbance increase of the UV spectrum indicated a hyperchromic effect due to albumin structure modifications during photolysis. TGA analysis of the photolysed activated carbons in the presence of BSA suggested that ozonized carbon samples underwent insertion of BSA upon photolysis, in particular the sample ozonized under dry conditions. The changes observed for the FTIR and elemental analysis agreed with this conclusion, which was further supported by (13)C SS-NMR, fluorescence emission and XPS. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. X-ray diffraction and reflectivity validation of the depletion attraction in the competitive adsorption of lung surfactant and albumin.

    PubMed

    Stenger, Patrick C; Wu, Guohui; Miller, Chad E; Chi, Eva Y; Frey, Shelli L; Lee, Ka Yee C; Majewski, Jaroslaw; Kjaer, Kristian; Zasadzinski, Joseph A

    2009-08-05

    Lung surfactant (LS) and albumin compete for the air-water interface when both are present in solution. Equilibrium favors LS because it has a lower equilibrium surface pressure, but the smaller albumin is kinetically favored by faster diffusion. Albumin at the interface creates an energy barrier to subsequent LS adsorption that can be overcome by the depletion attraction induced by polyethylene glycol (PEG) in solution. A combination of grazing incidence x-ray diffraction (GIXD), x-ray reflectivity (XR), and pressure-area isotherms provides molecular-resolution information on the location and configuration of LS, albumin, and polymer. XR shows an average electron density similar to that of albumin at low surface pressures, whereas GIXD shows a heterogeneous interface with coexisting LS and albumin domains at higher surface pressures. Albumin induces a slightly larger lattice spacing and greater molecular tilt, similar in effect to a small decrease in the surface pressure. XR shows that adding PEG to the LS-albumin subphase restores the characteristic LS electron density profile at the interface, and confirms that PEG is depleted near the interface. GIXD shows the same LS Bragg peaks and Bragg rods as on a pristine interface, but with a more compact lattice corresponding to a small increase in the surface pressure. These results confirm that albumin adsorption creates a physical barrier that inhibits LS adsorption, and that PEG in the subphase generates a depletion attraction between the LS aggregates and the interface that enhances LS adsorption without substantially altering the structure or properties of the LS monolayer.

  9. X-Ray Diffraction and Reflectivity Validation of the Depletion Attraction in the Competitive Adsorption of Lung Surfactant and Albumin

    PubMed Central

    Stenger, Patrick C.; Wu, Guohui; Miller, Chad E.; Chi, Eva Y.; Frey, Shelli L.; Lee, Ka Yee C.; Majewski, Jaroslaw; Kjaer, Kristian; Zasadzinski, Joseph A.

    2009-01-01

    Abstract Lung surfactant (LS) and albumin compete for the air-water interface when both are present in solution. Equilibrium favors LS because it has a lower equilibrium surface pressure, but the smaller albumin is kinetically favored by faster diffusion. Albumin at the interface creates an energy barrier to subsequent LS adsorption that can be overcome by the depletion attraction induced by polyethylene glycol (PEG) in solution. A combination of grazing incidence x-ray diffraction (GIXD), x-ray reflectivity (XR), and pressure-area isotherms provides molecular-resolution information on the location and configuration of LS, albumin, and polymer. XR shows an average electron density similar to that of albumin at low surface pressures, whereas GIXD shows a heterogeneous interface with coexisting LS and albumin domains at higher surface pressures. Albumin induces a slightly larger lattice spacing and greater molecular tilt, similar in effect to a small decrease in the surface pressure. XR shows that adding PEG to the LS-albumin subphase restores the characteristic LS electron density profile at the interface, and confirms that PEG is depleted near the interface. GIXD shows the same LS Bragg peaks and Bragg rods as on a pristine interface, but with a more compact lattice corresponding to a small increase in the surface pressure. These results confirm that albumin adsorption creates a physical barrier that inhibits LS adsorption, and that PEG in the subphase generates a depletion attraction between the LS aggregates and the interface that enhances LS adsorption without substantially altering the structure or properties of the LS monolayer. PMID:19651036

  10. Bioactivity of albumins bound to silver nanoparticles.

    PubMed

    Mariam, Jessy; Sivakami, S; Kothari, D C; Dongre, P M

    2014-06-01

    The last decade has witnessed a tremendous rise in the proposed applications of nanomaterials in the field of medicine due to their very attractive physiochemical properties and novel actions such as the ability to reach previously inaccessible targets such as brain. However biological activity of functional molecules bound to nanoparticles and its physiological consequences is still unclear and hence this area requires immediate attention. The functional properties of Human Serum Albumin (HSA) and Bovine Serum Albumin (BSA) bound to silver nanoparticles (~60 nm) have been studied under physiological environment. Esterase activity, binding of drugs (warfarin and ibuprofen), antioxidant activity and copper binding by albumins was evaluated. The catalytic efficiencies of HSA and BSA diminished upon binding to silver nanoparticles. Perturbation in binding of warfarin and ibuprofen, loss of free sulphydryls, antioxidant activity and enhancement of copper binding were observed in albumins bound to nanoparticles. These alterations in functional activity of nanoparticle bound albumins which will have important consequences should be taken into consideration while using nanoparticles for diagnostic and therapeutic purposes.

  11. Induced Long-Range Attractive Potentials of Human Serum Albumin by Ligand Binding

    SciTech Connect

    Sato, Takaaki; Komatsu, Teruyuki; Nakagawa, Akito; Tsuchida, Eishun

    2007-05-18

    Small-angle x-ray scattering and dielectric spectroscopy investigation on the solutions of recombinant human serum albumin and its heme hybrid revealed that heme incorporation induces a specific long-range attractive potential between protein molecules. This is evidenced by the enhanced forward intensity upon heme binding, despite no hindrance to rotatory Brownian motion, unbiased colloid osmotic pressure, and discontiguous nearest-neighbor distance, confirming monodispersity of the proteins. The heme-induced potential may play a trigger role in recognition of the ligand-filled human serum albumins in the circulatory system.

  12. Thermal effects of carbonated hydroxyapatite modified by glycine and albumin

    NASA Astrophysics Data System (ADS)

    Gerk, S. A.; Golovanova, O. A.; Kuimova, M. V.

    2017-01-01

    In this work calcium phosphate powders were obtained by precipitation method from simulated solutions of synovial fluid containing glycine and albumin. X-ray diffraction and IR spectroscopy determined that all samples are single-phase and are presented by carbonate containing hydroxyapatite (CHA). The thermograms of solid phases of CHA were obtained and analyzed; five stages of transformation in the temperature range of 25-1000°C were marked. It is shown that in this temperature range dehydration, decarboxylation and thermal degradation of amino acid and protein connected to the surface of solid phase occur. The tendency of temperature lowering of the decomposition of powders synthesized from a medium containing organic substances was determined. Results demonstrate a direct dependence between the concentration of the amino acid in a model solution and its content in the solid phase.

  13. Thermal effects of carbonated hydroxyapatite modified by glycine and albumin

    NASA Astrophysics Data System (ADS)

    Gerk, S. A.; Golovanova, O. A.; Kuimova, M. V.

    2017-01-01

    In this work calcium phosphate powders were obtained by precipitation method from simulated solutions of synovial fluid containing glycine and albumin. X-ray diffraction and IR spectroscopy determined that all samples are single-phase and are presented by carbonate containing hydroxyapatite (CHA). The thermograms of solid phases of CHA were obtained and analyzed; five stages of transformation in the temperature range of 25-1000°C were marked. It is shown that in this temperature range dehydration, decarboxylation and thermal degradation of amino acid and protein connected to the surface of solid phase occur. The tendency of temperature lowering of the decomposition of powders synthesized from a medium containing organic substances was determined. Results demonstrate a direct dependence between the concentration of the amino acid in a model solution and its content in the solid phase.

  14. Proximal Tubules Have the Capacity to Regulate Uptake of Albumin

    PubMed Central

    Wagner, Mark C.; Campos-Bilderback, Silvia B.; Chowdhury, Mahboob; Flores, Brittany; Lai, Xianyin; Myslinski, Jered; Pandit, Sweekar; Sandoval, Ruben M.; Wean, Sarah E.; Wei, Yuan; Satlin, Lisa M.; Wiggins, Roger C.; Witzmann, Frank A.

    2016-01-01

    Evidence from multiple studies supports the concept that both glomerular filtration and proximal tubule (PT) reclamation affect urinary albumin excretion rate. To better understand these roles of glomerular filtration and PT uptake, we investigated these processes in two distinct animal models. In a rat model of acute exogenous albumin overload, we quantified glomerular sieving coefficients (GSC) and PT uptake of Texas Red-labeled rat serum albumin using two-photon intravital microscopy. No change in GSC was observed, but a significant decrease in PT albumin uptake was quantified. In a second model, loss of endogenous albumin was induced in rats by podocyte-specific transgenic expression of diphtheria toxin receptor. In these albumin-deficient rats, exposure to diphtheria toxin induced an increase in albumin GSC and albumin filtration, resulting in increased exposure of the PTs to endogenous albumin. In this case, PT albumin reabsorption was markedly increased. Analysis of known albumin receptors and assessment of cortical protein expression in the albumin overload model, conducted to identify potential proteins and pathways affected by acute protein overload, revealed changes in the expression levels of calreticulin, disabled homolog 2, NRF2, angiopoietin-2, and proteins involved in ATP synthesis. Taken together, these results suggest that a regulated PT cell albumin uptake system can respond rapidly to different physiologic conditions to minimize alterations in serum albumin level. PMID:26054544

  15. Proximal Tubules Have the Capacity to Regulate Uptake of Albumin.

    PubMed

    Wagner, Mark C; Campos-Bilderback, Silvia B; Chowdhury, Mahboob; Flores, Brittany; Lai, Xianyin; Myslinski, Jered; Pandit, Sweekar; Sandoval, Ruben M; Wean, Sarah E; Wei, Yuan; Satlin, Lisa M; Wiggins, Roger C; Witzmann, Frank A; Molitoris, Bruce A

    2016-02-01

    Evidence from multiple studies supports the concept that both glomerular filtration and proximal tubule (PT) reclamation affect urinary albumin excretion rate. To better understand these roles of glomerular filtration and PT uptake, we investigated these processes in two distinct animal models. In a rat model of acute exogenous albumin overload, we quantified glomerular sieving coefficients (GSC) and PT uptake of Texas Red-labeled rat serum albumin using two-photon intravital microscopy. No change in GSC was observed, but a significant decrease in PT albumin uptake was quantified. In a second model, loss of endogenous albumin was induced in rats by podocyte-specific transgenic expression of diphtheria toxin receptor. In these albumin-deficient rats, exposure to diphtheria toxin induced an increase in albumin GSC and albumin filtration, resulting in increased exposure of the PTs to endogenous albumin. In this case, PT albumin reabsorption was markedly increased. Analysis of known albumin receptors and assessment of cortical protein expression in the albumin overload model, conducted to identify potential proteins and pathways affected by acute protein overload, revealed changes in the expression levels of calreticulin, disabled homolog 2, NRF2, angiopoietin-2, and proteins involved in ATP synthesis. Taken together, these results suggest that a regulated PT cell albumin uptake system can respond rapidly to different physiologic conditions to minimize alterations in serum albumin level.

  16. Albumin reduces the antibacterial activity of polyhexanide-biguanide-based antiseptics against Staphylococcus aureus and MRSA.

    PubMed

    Kapalschinski, N; Seipp, H M; Onderdonk, A B; Goertz, O; Daigeler, A; Lahmer, A; Lehnhardt, M; Hirsch, T

    2013-09-01

    Wound infection is one of the major complications in acute and chronic wound healing. Antiseptic solutions and wound irrigating agents are routinely used for therapy and prevention in healthcare today. Even if wound exudate contains total protein concentrations up to 9.3% and albumin concentrations up to 2.7% its influence to the antibacterial efficacy of these agents is barely investigated. This study analyzed the antibacterial effect of polyhexanide biguanide (PHMB) agents (PHMB-concentration 0.005-0.1%) against Staphylococcus aureus and methicillin-resistant-S. aureus (MRSA) after 2min incubation in presents of albumin in different concentrations (0-3%) in a standardized quantitative suspension assay. A significant decrease of the antibacterial activity against S. aureus was shown for a PHMB-concentration of 0.005% from 0.3% albumin (p<0.05), respectively highly significant from 0.75% (p<0.01) on. Thereby the loss of antimicrobial effect was presented as a linear correlation to the rising concentration of albumin. Furthermore a reduction of the antibacterial activity against MRSA in comparison to S. aureus was presented, for albumin concentrations from 3% on highly significant (p<0.01). The study showed that albumin causes a significant decrease of the antibacterial potency of PHMB-based antiseptics. Furthermore a diminished potency of the investigated substances for MRSA-contaminated wounds must be taken in consideration. If in vitro experiments show a significant decrease of antibacterial efficacy in the presence of albumin a sufficient activity of PHMB-based agents in clinical practice, especially in cases of exuding wounds or dried-up exudates, cannot be expected. Copyright © 2013 Elsevier Ltd and ISBI. All rights reserved.

  17. Polymerized soluble venom--human serum albumin

    SciTech Connect

    Patterson, R.; Suszko, I.M.; Grammer, L.C.

    1985-03-01

    Extensive previous studies have demonstrated that attempts to produce polymers of Hymenoptera venoms for human immunotherapy resulted in insoluble precipitates that could be injected with safety but with very limited immunogenicity in allergic patients. We now report soluble polymers prepared by conjugating bee venom with human serum albumin with glutaraldehyde. The bee venom-albumin polymer (BVAP) preparation was fractionated on Sephacryl S-300 to have a molecular weight range higher than catalase. /sup 125/I-labeled bee venom phospholipase A was almost completely incorporated into BVAP. Rabbit antibody responses to bee venom and bee venom phospholipase A were induced by BVAP. Human antisera against bee venom were absorbed by BVAP. No new antigenic determinants on BVAP were present as evidenced by absorption of antisera against BVAP by bee venom and albumin. BVAP has potential immunotherapeutic value in patients with anaphylactic sensitivity to bee venom.

  18. Use of urine albumin/creatinine ratio for estimation of proteinuria in cats and dogs.

    PubMed

    Kuwahar, Yasuhito; Nishii, Naohito; Takasu, Masaki; Ohba, Yasunori; Maeda, Sadatoshi; Kitagawa, Hitoshi

    2008-08-01

    The clinical utility of the urine albumin/creatinine ratio (UAC) using a simplified analyzer for estimation of proteinuria was studied in cats and dogs. Measurement results for diluted feline and canine albumin standard solutions showed linearity. Although conversion formulas (y=1.28x+1.04 and y=1.67x+10.47 for cats and dogs, respectively) were necessary, urine albumin concentrations could be determined in both animals. In cats and dogs with proteinuria, the UAC changed parallel with the urine protein/ creatinine ratio (UPC), and the Log UAC and Log UPC were significantly correlated (r=0.803 (p<0.01) in cats, r=0.801 (p<0.01) in dogs). The UAC using an UAC analyzer could be used clinically as one of the basic in-hospital laboratory tests for estimation of proteinuria in cats and dogs.

  19. Interaction of Water-Soluble CdTe Quantum Dots with Bovine Serum Albumin

    PubMed Central

    2011-01-01

    Semiconductor nanoparticles (quantum dots) are promising fluorescent markers, but it is very little known about interaction of quantum dots with biological molecules. In this study, interaction of CdTe quantum dots coated with thioglycolic acid (TGA) with bovine serum albumin was investigated. Steady state spectroscopy, atomic force microscopy, electron microscopy and dynamic light scattering methods were used. It was explored how bovine serum albumin affects stability and spectral properties of quantum dots in aqueous media. CdTe–TGA quantum dots in aqueous solution appeared to be not stable and precipitated. Interaction with bovine serum albumin significantly enhanced stability and photoluminescence quantum yield of quantum dots and prevented quantum dots from aggregating. PMID:27502633

  20. Bovine Serum Albumin binding to CoCrMo nanoparticles and the influence on dissolution

    NASA Astrophysics Data System (ADS)

    Simoes, T. A.; Brown, A. P.; Milne, S. J.; Brydson, R. M. D.

    2015-10-01

    CoCrMo alloys exhibit good mechanical properties, excellent biocompatibility and are widely utilised in orthopaedic joint replacements. Metal-on-metal hip implant degradation leads to the release of metal ions and nanoparticles, which persist through the implant's life and could be a possible cause of health complications. This study correlates preferential binding between proteins and metal alloy nanoparticles to the alloy's corrosion behaviour and the release of metal ions. TEM images show the formation of a protein corona in all particles immersed in albumin containing solutions. Only molybdenum release was significant in these tests, suggesting high dissolution of this element when CoCrMo alloy nanoparticles are produced as wear debris in the presence of serum albumin. The same trend was observed during extended exposure of molybdenum reference nanoparticles to albumin.

  1. THE INFLUENCE OF SALTS UPON THE IONISATION OF EGG ALBUMIN

    PubMed Central

    Sørensen, S. P. L.; Linderstrøm-Lang, K.; Lund, Ellen

    1927-01-01

    Introduction. A description is given of the principle followed in the experimental determination of the ionisation of egg albumin, its capacity to combine with acids and bases. Egg albumin is regarded as an ampholyte, and in accordance with J. N. Brønsted's definition of acids and bases, ampholytes are considered as substances capable of both taking up and giving off hydrogen ions. The theoretical treatment of the capacity of ampholytes to combine with acids (and bases) has been carried out on this basis. Section A. Several experimental series are noted, comprising the determination of the activity coefficient of the hydrogen ion (fH) in ammonium chloride solutions of different concentration. Section B. The general method of experimental determination of the ionisation (capacity to combine with adds and bases) of egg albumin in ammonium chloride and potassium chloride solutions is briefly described, and the results of the experiments are compared. Section C. 1). In a brief theoretical survey we have suggested that distinction should be made between isoelectric and isoionic reaction of an ampholyte, the former defined as the hydrogen ion activity (value of paH) at which the mean valency of the ampholyte is 0, the latter as the hydrogen ion activity at which the quantity of acid or base combined with the ampholyte is 0; or, as we prefer to express it, the hydrogen ion activity at which the specific hydrogen ionisation of the ampholyte is 0. If the ampholyte does not combine with other ions than the hydrogen ion, then isoelectric and isoionic reaction coincide. Isoionic reaction is determined by acid-combining experiments. The principle of this determination is briefly described. A theoretical investigation of the alteration with salt concentration of both isoelectric (isoionic) reaction and the shape and direction of the ionisation curves is made, with regard to ampholytes capable only of combining with hydrogen ions, on the basis of the Debye-Hückel formulæ and

  2. Preliminary crystallographic studies of four crystal forms of serum albumin

    NASA Technical Reports Server (NTRS)

    Carter, D. C.; Chang, B.; Ho, J. X.; Keeling, K.; Krishnasami, Z.

    1994-01-01

    Several crystal forms of serum albumin suitable for three-dimensional structure determination have been grown. These forms include crystals of recombinant and wild-type human serum albumin, baboon serum albumin, and canine serum albumin. The intrinsic limits of X-ray diffraction for these crystals are in the range 0.28-0.22 nm. Two of the crystal forms produced from human and canine albumin include incorporated long-chain fatty acids. Molecular replacement experiments have been successfully conducted on each crystal form using the previously determined atomic coordinates of human serum albumin illustrating the conserved tertiary structure.

  3. Preliminary crystallographic studies of four crystal forms of serum albumin

    NASA Technical Reports Server (NTRS)

    Carter, D. C.; Chang, B.; Ho, J. X.; Keeling, K.; Krishnasami, Z.

    1994-01-01

    Several crystal forms of serum albumin suitable for three-dimensional structure determination have been grown. These forms include crystals of recombinant and wild-type human serum albumin, baboon serum albumin, and canine serum albumin. The intrinsic limits of X-ray diffraction for these crystals are in the range 0.28-0.22 nm. Two of the crystal forms produced from human and canine albumin include incorporated long-chain fatty acids. Molecular replacement experiments have been successfully conducted on each crystal form using the previously determined atomic coordinates of human serum albumin illustrating the conserved tertiary structure.

  4. Albumin and pre-albumin levels do not reflect the nutritional status of female adolescents with restrictive eating disorders.

    PubMed

    Huysentruyt, Koen; De Schepper, Jean; Vanbesien, Jesse; Vandenplas, Yvan

    2016-04-01

    Albumin and pre-albumin are frequently used as nutritional markers in clinical practice. We examined whether serum albumin and pre-albumin were predicted by body mass index (BMI), hydration and/or inflammation in female adolescents with a recently diagnosed restrictive eating disorder (RED). This was a retrospective study of female adolescents with RED from 2002 to 2011. Low albumin and pre-albumin levels were defined as <3.5 g/dL and <20 mg/dL, respectively. We assessed inflammation using the erythrocyte sedimentation rate (ESR) and dehydration using the haematocrit levels. We included 75 females with a mean age of 15.2 years and 64% had a BMI Z score of <-2. The mean albumin and pre-albumin levels were 4.8 g/dL and 22.2 mg/dL, respectively, with 24% of the children having low pre-albumin and none having low albumin levels. The stepwise multiple regression for albumin identified ESR and haematocrit as significant predictors, which explained 14.8% of the variance. Age was the only significant predictor for pre-albumin, which explained 15.3% of the variance. Albumin, but not pre-albumin, levels were primarily predicted by low-grade inflammation and hydration, but not by BMI. These markers should not be used to assess nutritional status in adolescents with RED. ©2015 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  5. Synthetic nanoparticles of bovine serum albumin with entrapped salicylic acid

    PubMed Central

    Bronze-Uhle, ES; Costa, BC; Ximenes, VF; Lisboa-Filho, PN

    2017-01-01

    Bovine serum albumin (BSA) is highly water soluble and binds drugs or inorganic substances noncovalently for their effective delivery to various affected areas of the body. Due to the well-defined structure of the protein, containing charged amino acids, albumin nanoparticles (NPs) may allow electrostatic adsorption of negatively or positively charged molecules, such that substantial amounts of drug can be incorporated within the particle, due to different albumin-binding sites. During the synthesis procedure, pH changes significantly. This variation modifies the net charge on the surface of the protein, varying the size and behavior of NPs as the drug delivery system. In this study, the synthesis of BSA NPs, by a desolvation process, was studied with salicylic acid (SA) as the active agent. SA and salicylates are components of various plants and have been used for medication with anti-inflammatory, antibacterial, and antifungal properties. However, when administered orally to adults (usual dose provided by the manufacturer), there is 50% decomposition of salicylates. Thus, there has been a search for some time to develop new systems to improve the bioavailability of SA and salicylates in the human body. Taking this into account, during synthesis, the pH was varied (5.4, 7.4, and 9) to evaluate its influence on the size and release of SA of the formed NPs. The samples were analyzed using field-emission scanning electron microscopy, transmission electron microscopy, Fourier transform infrared, zeta potential, and dynamic light scattering. Through fluorescence, it was possible to analyze the release of SA in vitro in phosphate-buffered saline solution. The results of chemical morphology characterization and in vitro release studies indicated the potential use of these NPs as drug carriers in biological systems requiring a fast release of SA. PMID:28096662

  6. Electrostatic unfolding and interactions of albumin driven by pH changes: a molecular dynamics study.

    PubMed

    Baler, K; Martin, O A; Carignano, M A; Ameer, G A; Vila, J A; Szleifer, I

    2014-01-30

    A better understanding of protein aggregation is bound to translate into critical advances in several areas, including the treatment of misfolded protein disorders and the development of self-assembling biomaterials for novel commercial applications. Because of its ubiquity and clinical potential, albumin is one of the best-characterized models in protein aggregation research; but its properties in different conditions are not completely understood. Here, we carried out all-atom molecular dynamics simulations of albumin to understand how electrostatics can affect the conformation of a single albumin molecule just prior to self-assembly. We then analyzed the tertiary structure and solvent accessible surface area of albumin after electrostatically triggered partial denaturation. The data obtained from these single protein simulations allowed us to investigate the effect of electrostatic interactions between two proteins. The results of these simulations suggested that hydrophobic attractions and counterion binding may be strong enough to effectively overcome the electrostatic repulsions between the highly charged monomers. This work contributes to our general understanding of protein aggregation mechanisms, the importance of explicit consideration of free ions in protein solutions, provides critical new insights about the equilibrium conformation of albumin in its partially denatured state at low pH, and may spur significant progress in our efforts to develop biocompatible protein hydrogels driven by electrostatic partial denaturation.

  7. Adsorbed serum albumin is permissive to macrophage attachment to perfluorocarbon polymer surfaces in culture

    PubMed Central

    Godek, M.L.; Michel, R.; Chamberlain, L. M.; Castner, D. G.; Grainger, D.W.

    2013-01-01

    Monocyte/macrophage adhesion to biomaterials, correlated with foreign body response, occurs through protein-mediated surface interactions. Albumin-selective perfluorocarbon (FC) biomaterials are generally poorly cell-conducive due to insufficient receptor-mediated surface interactions, but macrophages bind to albumin-coated substrates and also preferentially to highly hydrophobic fluorinated surfaces. Bone marrow macrophages (BMMO) and IC-21, RAW 264.7 and J774A.1 monocyte/macrophage cells were cultured on FC surfaces. Protein deposition onto two distinct FC surfaces from complex and single-component solutions was tracked using fluorescence and time-of-flight secondary ion mass spectrometry (ToF-SIMS) methods. Cell adhesion and growth on protein pre-treated substrates were compared by light microscopy. Flow cytometry and integrin-directed antibody receptor blocking assessed integrins critical for monocyte/macrophage adhesion in vitro. Albumin predominantly adsorbs onto both FC surfaces from 10% serum. In cultures pre-adsorbed with albumin or serum-dilutions, BMMO responded similar to IC-21 at early time points. Compared to Teflon® AF, plasma-polymerized FC was less permissive to extended cell proliferation. The β2 integrins play major roles in macrophage adhesion to FC surfaces: antibody blocking significantly disrupted cell adhesion. Albumin-mediated cell adhesion mechanisms to FC surfaces could not be clarified. Primary BMMO and secondary IC-21 macrophages behave similarly on FC surfaces, regardless of pre-adsorbed protein biasing, with respect to adhesion, cell morphology, motility and proliferation. PMID:18306309

  8. Ischemia modified albumin (IMA) and albumin adjusted-IMA (AAIMA) as biomarkers for diabetic retinopathy.

    PubMed

    Reddy, Varikasuvu Seshadri; Sethi, Sumita; Agrawal, Poonam; Gupta, Navdeep; Garg, Renu

    2015-07-01

    Oxidative stress has important role in the pathophysiology of diabetic retinopathy (DR). Ischemia modified albumin (IMA) has been recently considered as a marker of oxidative damage in diabetes. However, there is scarcity of published information about both IMA and albumin adjusted-IMA (AAIMA) in DR patients. To evaluate the serum levels of IMA and AAIMA in patients with DR and in healthy controls. This was a cross sectional study. Serum was obtained to measure lipids, albumin and IMA from the the patients with DR and non-diabetic subjects. The IMA level was measured by a colorimetric albumin cobalt binding (ACB) assay and the values were presented as absorbance units (ABSU). The IMA levels were adjusted for albumin interference and the AAIMA by using a formula [Individual serum albumin/median albumin concentration of the population X IMA]. This study was done on 18 DR and 20 non- diabetic patients. The mean Serum IMA values in DR group and controls were 0.50±0.17 and 0.32±0.17, respectively (P=0.002). The mean serum AAIMA values in DR group and controls were 0.48±0.20 and 0.32±0.17, respectively (P=0.01). The albumin and HDL- Cholesterol levels were significantly lower in DR patients compared to controls (p=0.004 and p=0.01, respectively). The level of IMA and AAIMA were higher in cases of DR compared to that of non-diabetic subjects. The levels of albumin and HDL-Cholesterol were lower in DR patients compared to controls. © NEPjOPH.

  9. Capillary-based instrument for the simultaneous measurement of solution viscosity and solute diffusion coefficient at pressures up to 2000 bar and implications for ultrahigh pressure liquid chromatography.

    PubMed

    Kaiser, Theodore J; Thompson, J Will; Mellors, J Scott; Jorgenson, James W

    2009-04-15

    An instrument based on the Poiseuille flow principle capable of measuring solution viscosities at high pressures has been modified to observe UV-absorbent analytes in order to allow for the simultaneous measurement of analyte diffusivity. A capillary time-of-flight (CTOF) instrument was used to measure the viscosity of acetonitrile-water mixtures in all decade volume percent increments and the corresponding diffusion coefficients of small aromatic molecules in these solvent mixtures from atmospheric pressure to 2000 bar (approximately 30,000 psi) at 25 degrees C. The instrument works by utilizing a relatively small pressure drop (<100 bar) across a fused-silica capillary which has both the inlet and outlet pressurized so that the average column pressure can be significantly elevated (up to 2000 bar). Measurements with this instrument agree with high-pressure viscosity data collected previously using a CTOF viscometer, as well as with literature values obtained with falling-body viscometers of the Bridgman design. It has been further determined that, for the small molecules included in this study, trends in solute diffusivity with respect to pressure follow the predictions of the Stokes-Einstein equation when the solvent viscosity is corrected as a function of pressure. Because the instrument described herein determines viscosity and diffusivity independently, the effect of pressure on analyte hydrodynamic radius can also be monitored. An analysis of ultrahigh pressure liquid chromatography (UHPLC) data was performed using the pressure-corrected diffusion coefficient of hydroquinone to demonstrate the effect of this phenomenon on the analysis of chromatographic performance.

  10. A model comparing how rapidly transfusion of solvent detergent plasma restores clotting factors versus infusion of albumin-saline.

    PubMed

    Jilma-Stohlawetz, Petra; Kursten, Friedrich W; Horvath, Michaela; Leitner, Gerda; List, Jana; Marcek, Jana; Quehenberger, Peter; Schwameis, Michael; Bartko, Johann; Jilma, Bernd

    2015-12-01

    A recent randomized controlled trial demonstrated the bioequivalence between universally applicable and AB0 compatible transfusion plasma in healthy volunteers. There was a limited change in coagulation factor levels and inhibitors before and after plasmapheresis and subsequent plasma transfusion. The aim of this extension trial was to investigate the true capacity of these plasma products to restore baseline levels of coagulation factors and inhibitors after plasma depletion in comparison to haemodilution induced by infusion of albumin solution. Fourteen healthy subjects, who completed both plasma transfusion periods, underwent an additional plasmapheresis (600 mL) followed by an infusion of 1200 mL albumin (3.125%) in a third period. The fibrinogen levels, as well as other clotting factors (FII, FV, FVII and FXI), decreased by 10% after plasmapheresis, and subsequent infusion of albumin solution further aggravated this drop in clotting factors to approximately 20-25%. The clotting factors with a long half-life were not even restored 24 hours after infusion of albumin solution, whereas those with a short half-life were replenished by endogenous synthesis within 24 hours. In contrast, transfusion of either plasma product rapidly restored all clotting parameters and inhibitors (protein S and plasmin inhibitor) immediately after transfusion. This study demonstrates that albumin solution induces an enhanced dilution of clotting factors and inhibitors, whereas both plasma products quickly compensated for the experimental loss of these plasma proteins. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  11. Characterization of isomeric VX nerve agent adducts on albumin in human plasma using liquid chromatography-tandem mass spectrometry.

    PubMed

    Saeidian, Hamid; Mirkhani, Valioallah; Mousavi Faraz, Sajjad; Taghi Naseri, Mohammad; Babri, Mehran

    2015-01-01

    This study includes the characterization of isomeric VX organophosphorus adducts on albumin in human plasma using liquid chromatography-tandem mass spectrometry (LC-MS/MS). VX or its structural isomers were spiked into a vial containing plasma in order to obtain phosphorylated albumin. After pronase and trypsin digestion, the resulting solutions were analyzed to confirm adduct formation with the amino acid tyrosine on the albumin in human plasma. The LC-MS/MS experiments show that VX and its isomers can be attached to tyrosine on the albumin in human blood. Mass spectrometric studies revealed some interesting fragmentation pathways during the ionization process, such as ethylene, formic acid and ammonia elimination and an intermolecular electrophilic aromatic substitution reaction. The proposed mechanisms for the formation of the fragments were confirmed through the analysis of fragments of deuterated adducts.

  12. Albumin modulates lateral assembly of fibrin polymers: evidence of enhanced fine fibril formation and of unique synergism with fibrinogen

    SciTech Connect

    Galanakis, D.K.; Lane, B.P.; Simon, S.R.

    1987-04-21

    The authors identified a new property of human albumin. It enhances formation of fine fibril (or leptofibril) structure during fibrin gelation, and by nephelometric and electron microscopic measurements, this property is independent of and synergistic with that of fibrinogen. They examined fibrin aggregation using physiologic temperatures and pH and albumin:fibrin concentration ratios below those at which the known accelerating effect on fibrin aggregation occurs. An albumin concentration dependent decrease in gel turbidity maxima was consistently demonstrable in buffers containing or lacking (2-5 mM) CaCl/sub 2/. Electron microscopic measurements of cross-sectional fibril widths, performed on sections of glutaraldehyde-fixed gels, disclosed differences between albumin-containing and control gels which were significant. Spin-labeled albumin displayed no change in electron (para) magnetic spin resonance spectral measurements during its inhibition of fibrin, indicating no perturbation on albumin conformation in the vicinities of Cys-34 and of fatty acid binding sites. Certain fibrinogen:albumin ratios designed to induce maximal inhibition yet permit gelation in the presence of either alone prevented gelation of buffer-diluted fibrin monomers. Aliquots from these which were dried and negatively stained on formvar-coated grids disclosed strands of 5-17 nm width, most displaying a 60-250-nm approximate length. The amounts of /sup 131/I-labeled coagulable fibrin which remained soluble in fibrinogen solutions were increased by albumin. They conclude that albumin enhances formation of leptofibril-rich gel domains when other plasma factors favor formation of such structures. Available evidence indicating decreased permeability implies that such gel domains limit efflux rates from the intrathrombus environment and from intra- to extravascular space.

  13. Glycine exists mainly as monomers, not dimers, in supersaturated aqueous solutions: implications for understanding its crystallization and polymorphism.

    PubMed

    Huang, Jun; Stringfellow, Thomas C; Yu, Lian

    2008-10-22

    Glycine, the simplest amino acid, is described as existing as hydrogen-bonded cyclic dimers in supersaturated aqueous solutions and, as a result, crystallizing in a centrosymmetric polymorph (polymorph alpha) for which the dimer can be viewed as the building unit, in favor of other polymorphs of polar structures. In exhibiting this relation between polymorphic selectivity and self-association in solution, glycine is thought to illustrate a general principle. We measured the freezing-point depression of glycine-water up to 30% supersaturation and found that glycine exists mainly as monomers, not dimers, and that the dimer stability constant K D is smaller than 0.1 kg of H 2O/mol if the observed osmotic abnormality is attributed to dimerization. We also revisited a report cited as evidence for glycine dimerization: the slowdown of glycine diffusion with solution age. Pulsed gradient spin-echo NMR spectroscopy was used in place of the previous method of Gouy interferometry to avoid perturbations to sloution structure caused by the interdiffusion between two solutions of different concentrations. No aging effect was observed on glycine diffusion up to 24% supersaturation after five days. The solute size calculated from diffusivity, viscosity, and the Stokes-Einstein relation showed no increase with concentration or solution age. We conclude that glycine exists in supersaturated aqueous solutions mainly as monomers, not dimers, and remains so upon aging. This result does not invalidate the theories of how pH and additives affect glycine's polymorphic preference, because they begin with the assumption that alpha glycine is the preferred polymorph under normal conditions, but requires a new explanation for that assumption itself.

  14. Cubic exact solutions for the estimation of pairwise haplotype frequencies: implications for linkage disequilibrium analyses and a web tool 'CubeX'

    PubMed Central

    Gaunt, Tom R; Rodríguez, Santiago; Day, Ian NM

    2007-01-01

    Background The frequency of a haplotype comprising one allele at each of two loci can be expressed as a cubic equation (the 'Hill equation'), the solution of which gives that frequency. Most haplotype and linkage disequilibrium analysis programs use iteration-based algorithms which substitute an estimate of haplotype frequency into the equation, producing a new estimate which is repeatedly fed back into the equation until the values converge to a maximum likelihood estimate (expectation-maximisation). Results We present a program, "CubeX", which calculates the biologically possible exact solution(s) and provides estimated haplotype frequencies, D', r2 and χ2 values for each. CubeX provides a "complete" analysis of haplotype frequencies and linkage disequilibrium for a pair of biallelic markers under situations where sampling variation and genotyping errors distort sample Hardy-Weinberg equilibrium, potentially causing more than one biologically possible solution. We also present an analysis of simulations and real data using the algebraically exact solution, which indicates that under perfect sample Hardy-Weinberg equilibrium there is only one biologically possible solution, but that under other conditions there may be more. Conclusion Our analyses demonstrate that lower allele frequencies, lower sample numbers, population stratification and a possible |D'| value of 1 are particularly susceptible to distortion of sample Hardy-Weinberg equilibrium, which has significant implications for calculation of linkage disequilibrium in small sample sizes (eg HapMap) and rarer alleles (eg paucimorphisms, q < 0.05) that may have particular disease relevance and require improved approaches for meaningful evaluation. PMID:17980034

  15. Cubic exact solutions for the estimation of pairwise haplotype frequencies: implications for linkage disequilibrium analyses and a web tool 'CubeX'.

    PubMed

    Gaunt, Tom R; Rodríguez, Santiago; Day, Ian Nm

    2007-11-02

    The frequency of a haplotype comprising one allele at each of two loci can be expressed as a cubic equation (the 'Hill equation'), the solution of which gives that frequency. Most haplotype and linkage disequilibrium analysis programs use iteration-based algorithms which substitute an estimate of haplotype frequency into the equation, producing a new estimate which is repeatedly fed back into the equation until the values converge to a maximum likelihood estimate (expectation-maximisation). We present a program, "CubeX", which calculates the biologically possible exact solution(s) and provides estimated haplotype frequencies, D', r2 and chi2 values for each. CubeX provides a "complete" analysis of haplotype frequencies and linkage disequilibrium for a pair of biallelic markers under situations where sampling variation and genotyping errors distort sample Hardy-Weinberg equilibrium, potentially causing more than one biologically possible solution. We also present an analysis of simulations and real data using the algebraically exact solution, which indicates that under perfect sample Hardy-Weinberg equilibrium there is only one biologically possible solution, but that under other conditions there may be more. Our analyses demonstrate that lower allele frequencies, lower sample numbers, population stratification and a possible |D'| value of 1 are particularly susceptible to distortion of sample Hardy-Weinberg equilibrium, which has significant implications for calculation of linkage disequilibrium in small sample sizes (eg HapMap) and rarer alleles (eg paucimorphisms, q < 0.05) that may have particular disease relevance and require improved approaches for meaningful evaluation.

  16. 21 CFR 866.5040 - Albumin immunological test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... the reagents used to measure by immunochemical techniques the albumin (a plasma protein) in serum and other body fluids. Measurement of albumin aids in the diagnosis of kidney and intestinal diseases....

  17. A reference system for urinary albumin: current status.

    PubMed

    Lieske, John C; Bondar, Olga; Miller, W Greg; Bachmann, Lorin M; Narva, Andrew S; Itoh, Yoshihisa; Zegers, Ingrid; Schimmel, Heinz; Phinney, Karen; Bunk, David M

    2013-05-01

    Increased urinary excretion of albumin reflects kidney damage and is a recognized risk factor for progression of renal and cardiovascular disease. Considerable inter-method differences have been reported for both albumin and creatinine measurement results, and therefore the albumin-to-creatinine ratio. Measurement accuracy is unknown and there are no independent reference measurement procedures for albumin and no reference materials for either measurand in urine. The National Kidney Disease Education Program (NKDEP) Laboratory Working Group and the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) have initiated joint projects to facilitate standardization of urinary albumin and creatinine measurement. A candidate LC-MS/MS reference measurement procedure for urinary albumin and candidate reference materials for urinary albumin and creatinine has been developed. The status of validations of these reference system components is reported. The development of certified reference materials and reference measurement procedures for urinary albumin will enable standardization of this important measurand.

  18. Interaction of amphiphilic drugs with human and bovine serum albumins

    NASA Astrophysics Data System (ADS)

    Khan, Abbul Bashar; Khan, Javed Masood; Ali, Mohd. Sajid; Khan, Rizwan Hasan; Kabir-ud-Din

    2012-11-01

    To know the interaction of amphiphilic drugs nortriptyline hydrochloride (NOT) and promazine hydrochloride (PMZ) with serum albumins (i.e., human serum albumin (HSA) and bovine serum albumin (BSA)), techniques of UV-visible, fluorescence, and circular dichroism (CD) spectroscopies are used. The binding affinity is more in case of PMZ with both the serum albumins. The quenching rate constant (kq) values suggest a static quenching process for all the drug-serum albumin interactions. The UV-visible results show that the change in protein conformation of PMZ-serum albumin interactions are more prominent as compared to NOT-serum albumin interactions. The CD results also explain the conformational changes in the serum albumins on binding with the drugs. The increment in %α-helical structure is slightly more for drug-BSA complexes as compared to drug-HSA complexes.

  19. Interaction of amphiphilic drugs with human and bovine serum albumins.

    PubMed

    Khan, Abbul Bashar; Khan, Javed Masood; Ali, Mohd Sajid; Khan, Rizwan Hasan; Kabir-Ud-Din

    2012-11-01

    To know the interaction of amphiphilic drugs nortriptyline hydrochloride (NOT) and promazine hydrochloride (PMZ) with serum albumins (i.e., human serum albumin (HSA) and bovine serum albumin (BSA)), techniques of UV-visible, fluorescence, and circular dichroism (CD) spectroscopies are used. The binding affinity is more in case of PMZ with both the serum albumins. The quenching rate constant (k(q)) values suggest a static quenching process for all the drug-serum albumin interactions. The UV-visible results show that the change in protein conformation of PMZ-serum albumin interactions are more prominent as compared to NOT-serum albumin interactions. The CD results also explain the conformational changes in the serum albumins on binding with the drugs. The increment in %α-helical structure is slightly more for drug-BSA complexes as compared to drug-HSA complexes.

  20. Interaction of Citrinin with Human Serum Albumin

    PubMed Central

    Poór, Miklós; Lemli, Beáta; Bálint, Mónika; Hetényi, Csaba; Sali, Nikolett; Kőszegi, Tamás; Kunsági-Máté, Sándor

    2015-01-01

    Citrinin (CIT) is a mycotoxin produced by several Aspergillus, Penicillium, and Monascus species. CIT occurs worldwide in different foods and drinks and causes health problems for humans and animals. Human serum albumin (HSA) is the most abundant plasma protein in human circulation. Albumin forms stable complexes with many drugs and xenobiotics; therefore, HSA commonly plays important role in the pharmacokinetics or toxicokinetics of numerous compounds. However, the interaction of CIT with HSA is poorly characterized yet. In this study, the complex formation of CIT with HSA was investigated using fluorescence spectroscopy and ultrafiltration techniques. For the deeper understanding of the interaction, thermodynamic, and molecular modeling studies were performed as well. Our results suggest that CIT forms stable complex with HSA (logK ~ 5.3) and its primary binding site is located in subdomain IIA (Sudlow’s Site I). In vitro cell experiments also recommend that CIT-HSA interaction may have biological relevance. Finally, the complex formations of CIT with bovine, porcine, and rat serum albumin were investigated, in order to test the potential species differences of CIT-albumin interactions. PMID:26633504

  1. Lymphatic albumin clearance from psoriatic skin

    SciTech Connect

    Staberg, B.; Klemp, P.; Aasted, M.; Worm, A.M.; Lund, P.

    1983-12-01

    In nine patients with untreated psoriasis vulgaris, human serum albumin labelled with /sup 125/I or /sup 131/I was injected intradermally in symmetrically located involved and uninvolved skin. The activity of the depots was followed by external detection, and the arrival of labelled albumin in plasma was monitored. In involved psoriatic skin the local mean half-time (T1/2) for tracer disappearance was 20.8 +/- 8.2 (S.D.) hr and in clinically normal skin, 29.1 +/- 9.6 (S.D.) hr. The difference was significant (p less than 0.002). Accordingly, the tracer from involved skin reached higher plasma levels than the tracer from uninvolved skin. However, under slight lymphatic stasis the appearance rate of radiolabelled albumin in plasma from both tissues was minimal during 1 to 2 hours after the injection, indicating that a local direct transvascular drainage of plasma albumin from the interstitium of diseased and normal skin was negligible. We conclude that the previously demonstrated increased extravasation of plasma proteins in involved psoriatic skin is compensated by an increased lymphatic drainage of plasma proteins, and not by an increased local transvascular return.

  2. Albumin holograms with gentian violet dye

    NASA Astrophysics Data System (ADS)

    Olivares-Pérez, A.; Dorantes-García, V.; Ortiz-Gutiérrez, Mauricio; Toxqui-López, Santa; Ordoñez-Padilla, Manuel J.; Mejias-Brizuela, Nildia Y.

    2017-03-01

    Transmission holograms made with egg's albumin, used as a matrix and violet of gentian as dye, and ammonium dichromate as sensitizers. Behavior is outlined of the diffraction efficiency of gratings based on the parameters of exposure energy, and thickness. All the gratings were recorded at line 442 nm of laser He-Cd.

  3. Albumin-Based Nanodevices as Drug Carriers.

    PubMed

    Loureiro, Ana; Azoia, Nuno G; Gomes, Andreia C; Cavaco-Paulo, Artur

    2016-01-01

    Nanomedicine, the application of nanotechnology to medicine, is being increasingly used to improve and exploit the advantages of efficient drug delivery. Different nanodevices have been developed in recent years, among them protein-based nanoparticles which have gained considerable interest. Albumin is a versatile protein carrier with several characteristics that make it an ideal candidate for drug delivery, such as its availability, its biocompatibility, its biodegradability, and its lack of toxicity and immunogenicity. This review embodies an overview of different methods available for production of albumin-based nanoparticles, with focus on high-energy emulsification methods. A comparison between production by using sonication, which involves acoustic cavitation, and the high pressure homogenization method, where occurs hydrodynamic cavitation, is presented. Taking into account important properties of nanoparticles required for intravenous administration, the use of poloxamers, tri-block copolymer surfactants is discussed as it improves blood circulation time and bioavailability of nanoparticles. Thus, nanoparticles can be engineered to provide adequate features to therapeutic applications, in which can be included surface functionalization with targeting agents. Different albumin-based formulations and their therapeutic applications are presented in this review, with emphasis on applications in cancer therapy, where albumin-based strategies are promising for targeted drug delivery in innovative clinical strategies.

  4. [Current role of albumin in critical care].

    PubMed

    Aguirre Puig, P; Orallo Morán, M A; Pereira Matalobos, D; Prieto Requeijo, P

    2014-11-01

    The use of colloids in fluid therapy has been, and still continues to be a controversial topic, particularly when referring to the critical patient. The choice of the fluid that needs to be administered depends on several factors, many of which are theoretical, and continue being an object of debate. The interest in the clinical use of the albumin has emerged again, immediately after recent publications in the search of the most suitable colloid. It is the most abundant protein in the plasma, being responsible for 80% of the oncotic pressure. It regulates the balance between the intra- and extra-vascular volumes. Recent multicenter studies question the supposed lack of safety that was previously assigned to it. Furthermore, in vitro studies demonstrate other important actions besides oncotic, for example neutralization of free radicals, and exogenous (drugs) and endogenous substances (bile pigments, cholesterol). Being aware of these secondary properties of albumin, and evaluating the pathophysiology of the critical patient (in particular, sepsis), to maintain plasma albumin levels within the normal range, could be of great importance. Based on the most recent publications, the aim of this review is to briefly analyze the pathophysiology of albumin, as well as to discuss its possible indications in the critical patient.

  5. Design of Albumin-Coated Microbubbles Loaded With Polylactide Nanoparticles.

    PubMed

    Gauthier, Marianne; Yin, Qian; Cheng, Jianjun; O'Brien, William D

    2015-08-01

    A protocol was designed to produce albumin-coated microbubbles (MBs) loaded with functionalized polylactide (PLA) nanoparticles (NPs) for future drug delivery studies. Microbubbles resulted from the sonication of 5% bovine serum albumin and 15% dextrose solution. Functionalized NPs were produced by mixing fluorescent PLA and PLA-polyethylene glycol-carboxylate conjugates. Nanoparticle-loaded MBs resulted from the covalent conjugation of functionalized NPs and MBs. Three NP/MB volume ratios (1/1, 1/10, and 1/100) and unloaded MBs were produced and compared. Statistical evaluations were based on quantitative analysis of 3 parameters at 4 time points (1, 4, 5, and 6 days post MB fabrication): MB diameter using a circle detection routine based on the Hough transform, MB number density using a hemocytometer, and NP-loading yield based on MB counts from fluorescence and light microscopic images. Loading capacity of the albumin-coated MBs was evaluated by fluorescence. Loaded MB sizes were stable over 6 days after production and were not significantly different from that of time-matched unloaded MBs. Number density evaluation showed that only 1/1 NP/MB volume ratio and unloaded MB number densities were stable over time, and that the 1/1 MB number density evaluated at each time point was not significantly different from that of unloaded MBs. The 1/10 and 1/100 NP/MB volume ratios had unstable number densities that were significantly different from that of unloaded MBs (P < .05). Fluorescence evaluation suggested that 1/1 MBs had a higher NP-loading yield than 1/10 and 1/100 MBs. Quantitative loading evaluation suggested that the 1/1 MBs had a loading capacity of 3700 NPs/MB. A protocol was developed to load albumin MBs with functionalized PLA NPs for further drug delivery studies. The 1/1 NP/MB volume ratio appeared to be the most efficient to produce stable loaded MBs with a loading capacity of 3700 NPs/MB. © 2015 by the American Institute of Ultrasound in Medicine.

  6. Design of Albumin-Coated Microbubbles Loaded With Polylactide Nanoparticles

    PubMed Central

    Gauthier, Marianne; Yin, Qian; Cheng, Jianjun; O'Brien, William D.

    2015-01-01

    Objectives A protocol was designed to produce albumin-coated microbubbles (MBs) loaded with functionalized polylactide (PLA) nanoparticles (NPs) for future drug delivery studies. Methods Microbubbles resulted from the sonication of 5% bovine serum albumin and 15% dextrose solution. Functionalized NPs were produced by mixing fluorescent PLA and PLA-polyethylene glycol-carboxylate conjugates. Nanoparticle-loaded MBs resulted from the covalent conjugation of functionalized NPs and MBs. Three NP/MB volume ratios (1/1, 1/10, and 1/100) and unloaded MBs were produced and compared. Statistical evaluations were based on quantitative analysis of 3 parameters at 4 time points (1, 4, 5, and 6 days post MB fabrication): MB diameter using a circle detection routine based on the Hough transform, MB number density using a hemocytometer, and NP-loading yield based on MB counts from fluorescence and light microscopic images. Loading capacity of the albumin-coated MBs was evaluated by fluorescence. Results Loaded MB sizes were stable over 6 days after production and were not significantly different from that of time-matched unloaded MBs. Number density evaluation showed that only 1/1 NP/MB volume ratio and unloaded MB number densities were stable over time, and that the 1/1 MB number density evaluated at each time point was not significantly different from that of unloaded MBs. The 1/10 and 1/100 NP/MB volume ratios had unstable number densities that were significantly different from that of unloaded MBs (P < .05). Fluorescence evaluation suggested that 1/1 MBs had a higher NP-loading yield than 1/10 and 1/100 MBs. Quantitative loading evaluation suggested that the 1/1 MBs had a loading capacity of 3700 NPs/MB. Conclusions A protocol was developed to load albumin MBs with functionalized PLA NPs for further drug delivery studies. The 1/1 NP/MB volume ratio appeared to be the most efficient to produce stable loaded MBs with a loading capacity of 3700 NPs/MB. PMID:26206822

  7. Impacts of albumin synergized with hydroxyethyl starch on early microvascular albumin leakage after major abdominal surgery in rabbits.

    PubMed

    Li, Weiming; Xu, Pengyuan; Cen, Yunyun; Sun, Dali; Yang, Ting; Xu, Qingwen; Li, Shumin; Li, Yijun; Ding, Bo

    2017-02-01

    To investigate the impacts of albumin synergized with hydroxyethyl starch (HES) on early microvascular albumin leakage after major abdominal surgery in rabbits. Forty male Japanese rabbits were randomly divided into four groups: the control group, the saline group, the albumin group, and the Syn group (hydroxyethyl starch+albumin). The latter three groups were performed gastrectomy plus resection of pancreatic body and tail and splenectomy. The serum albumin concentration was detected before and 48h after surgery, and the conditions of mesenteric microvascular leakage in these 4 groups were observed under microscope 48 h after surgery to calculate the leakage rate. Compared with the saline group, the albumin group and the Syn group exhibited significantly increased serum albumin concentrations 48h after surgery (P<0.05). The albumin leakage rate was the most obvious in the albumin group, followed by the saline group, while that in the Syn group was the minimal, and there existed significant differences among these groups (P<0.05) . Simple administration of albumin in the early stage after major abdominal surgery could increase the albumin leakage, while the synergization of albumin and hydroxyethyl starch could reduce the albumin leakage.

  8. Peritoneal Albumin Dialysis as a Novel Approach for Liver Support: Study in a Porcine Model of Acute Hepatic Failure.

    PubMed

    Defterevos, Georgios; Nastos, Constantinos; Papalois, Apostolos; Kalimeris, Konstantinos; Margelos, Vassileios; Fragulidis, George; Pafiti, Agathi; Mikrovas, Aggeliki; Nomikos, Tzortzis; Smyrniotis, Vassilios; Arkadopoulos, Nikolaos

    2016-08-01

    Artificial liver support gained considerable interest in recent years due to the development of various albumin dialysis systems, which prolong survival of some patients with acute liver failure (ALF). Τhis study aims to examine the role of peritoneal albumin dialysis in a postoperative ALF model. ALF was induced in 14 female Landrace pigs by a combination of major liver resection (70-75% of total parenchyma) and ischemic-reperfusion injury on the liver remnant. Animals were randomly divided in two groups (n = 7 each). Both were monitored for 12 h of reperfusion and received peritoneal dialysis for 6 h, beginning 6 h after reperfusion. The albumin group received an albumin-rich solution and the control group received albumin-free solution. The control group gradually developed intracranial hypertension, whereas, in the albumin group, rise in the intracranial pressure was substantially attenuated (P < 0.01, t = 12 h). Albumin-treated animals had significantly lower levels of ammonia (P < 0.01), total bile acids (P < 0.01), free fatty acids (P < 0.05), lactate (P < 0.01), and total bilirubin (P < 0.05). Liver malondialdehyde and protein carbonyl were significantly reduced (P = 0.007 and P = 0.001 at t = 12 h) after albumin dialysis. Results suggest that this method may become a useful adjunct in the management of ALF, thus, justifying further study. © 2016 Wiley Periodicals, Inc. and International Center for Artificial Organs and Transplantation.

  9. Phase Separation in Solutions of Monoclonal Antibodies

    NASA Astrophysics Data System (ADS)

    Benedek, George; Wang, Ying; Lomakin, Aleksey; Latypov, Ramil

    2012-02-01

    We report the observation of liquid-liquid phase separation (LLPS) in a solution of humanized monoclonal antibodies, IgG2, and the effects of human serum albumin, a major blood protein, on this phase separation. We find a significant reduction of phase separation temperature in the presence of albumin, and a preferential partitioning of the albumin into the antibody-rich phase. We provide a general thermodynamic analysis of the antibody-albumin mixture phase diagram and relate its features to the magnitude of the effective inter-protein interactions. Our analysis suggests that additives (HSA in this report), which have moderate attraction with antibody molecules, may be used to forestall undesirable protein condensation in antibody solutions. Our findings are relevant to understanding the stability of pharmaceutical solutions of antibodies and the mechanisms of cryoglobulinemia.

  10. Albumin and Ricinus communis agglutinin decrease endothelial permeability via interactions with matrix.

    PubMed

    Qiao, R; Siflinger-Birnboim, A; Lum, H; Tiruppathi, C; Malik, A B

    1993-08-01

    We studied the effects of albumin and the lectin Ricinus communis agglutinin (RCA) on hydraulic conductivity (Lp) of bovine pulmonary microvascular endothelial cell monolayers (BPMVEC) because of the evidence that albumin and RCA can interfere with transendothelial albumin permeability (Siflinger-Birnboim, A., J. Schnitzer, H. Lum, F. Blumenstock, C. Shen, P. Del Vecchio, and A. Malik. J. Cell. Physiol. 149: 575-584, 1991). BPMVEC were seeded on microporous polycarbonate filters, and the liquid flux was measured by collecting effluent into a tubing of known inner diameter at transendothelial hydrostatic pressures (P) ranging from 5 to 20 cmH2O. Lp was calculated as the slope of the relationship of liquid flux per unit surface area (Jv) vs. P. Addition of RCA (50 micrograms/ml) or albumin (5 mg/ml) to the endothelial cell medium containing albumin-free Hanks' balanced saline solution (HBSS) decreased total Lp (expressed x 10(-6) cm.s-1 x cmH2O-1) from 17.2 +/- 3.6 during HBSS to 4.7 +/- 0.9 during albumin and 5.7 +/- 1.6 during RCA (P < 0.01 for both). The RCA effect, but not that of albumin, was prevented by the addition of D-galactose (0.1 M) (the cognate hapten monosaccharide of RCA). We determined the contribution of the extracellular matrix (ECM) in decreasing the Lp by obtaining ECM after treatment of the monolayers with 0.025 M NH4OH to detach endothelial cells from the ECM. Basal ECM Lp (expressed x 10(-6) cm.s-1 x cmH2O-1) was 57.0 +/- 15.3, and it decreased to 19.7 +/- 4.3 and 17.5 +/- 2.9 during RCA and albumin, respectively (P < 0.01 for both). In contrast, RCA and albumin did not alter the filter Lp values. Another lectin, Ulex europaeus agglutinin, and the protein immunoglobulin G had no effect on Lp values.(ABSTRACT TRUNCATED AT 250 WORDS)

  11. Pseudo-esterase Activity of Human Albumin

    PubMed Central

    Lockridge, Oksana; Xue, Weihua; Gaydess, Andrea; Grigoryan, Hasmik; Ding, Shi-Jian; Schopfer, Lawrence M.; Hinrichs, Steven H.; Masson, Patrick

    2008-01-01

    Human albumin is thought to hydrolyze esters because multiple equivalents of product are formed for each equivalent of albumin. Esterase activity with p-nitrophenyl acetate has been attributed to turnover at tyrosine 411. However, p-nitrophenyl acetate creates multiple, stable, acetylated adducts, a property contrary to turnover. Our goal was to identify residues that become acetylated by p-nitrophenyl acetate and determine the relationship between stable adduct formation and turnover. Fatty acid-free human albumin was treated with 0.5 mm p-nitrophenyl acetate for 5 min to 2 weeks, or with 10 mm p-nitrophenyl acetate for 48 h to 2 weeks. Aliquots were digested with pepsin, trypsin, or GluC and analyzed by mass spectrometry to identify labeled residues. Only Tyr-411 was acetylated within the first 5 min of reaction with 0.5 mm p-nitrophenyl acetate. After 0.5–6 h there was partial acetylation of 16–17 residues including Asp-1, Lys-4, Lys-12, Tyr-411, Lys-413, and Lys-414. Treatment with 10 mm p-nitrophenyl acetate resulted in acetylation of 59 lysines, 10 serines, 8 threonines, 4 tyrosines, and Asp-1. When Tyr-411 was blocked with diisopropylfluorophosphate or chlorpyrifos oxon, albumin had normal esterase activity with β-naphthyl acetate as visualized on a nondenaturing gel. However, after 82 residues had been acetylated, esterase activity was almost completely inhibited. The half-life for deacetylation of Tyr-411 at pH 8.0, 22 °C was 61 ± 4 h. Acetylated lysines formed adducts that were even more stable. In conclusion, the pseudo-esterase activity of albumin is the result of irreversible acetylation of 82 residues and is not the result of turnover. PMID:18577514

  12. Potential of mean force between hydrophobic solutes in the Jagla model of water and implications for cold denaturation of proteins.

    PubMed

    Maiti, Moumita; Weiner, Saul; Buldyrev, Sergey V; Stanley, H Eugene; Sastry, Srikanth

    2012-01-28

    Using the Jagla model potential we calculate the potential of mean force (PMF) between hard sphere solutes immersed in a liquid displaying water-like properties. Consistent estimates of the PMF are obtained by (a) umbrella sampling, (b) calculating the work done by the mean force acting on the hard spheres as a function of their separation, and (c) determining the position dependent chemical potential after calculating the void space in the liquid. We calculate the PMF for an isobar along which cold denaturation of a model protein has previously been reported. We find that the PMF at contact varies non-monotonically, which is consistent with the observed cold denaturation. The Henry constant also varies non-monotonically with temperature. We find, on the other hand, that a second (solvent separated) minimum of the PMF becomes deeper as temperature decreases. We calculate the solvent-solvent pair correlation functions for solvents near the solute and in the bulk, and show that, as temperature decreases, the two pair correlation functions become indistinguishable, suggesting that the perturbation of solvent structure by the solute diminishes as temperature decreases. The solvent-solute pair correlation function at contact grows as the temperature decreases. We calculate the cavity correlation function and show the development of a solvent-separated peak upon decrease of temperature. These observations together suggest that cold denaturation occurs when the solvent penetrates between hydrophobic solutes in configurations with favorable free energy. Our results thus suggest that cold denatured proteins are structured and that cold denaturation arises from strong solvent-solute interactions, rather than from entropic considerations as in heat denaturation. © 2012 American Institute of Physics

  13. Relationship of two lacustrine ostracode species to solute composition and salinity: implications for paleohydrochemistry ( Limnocythere sappaensis/staplini).

    USGS Publications Warehouse

    Forester, R.M.

    1983-01-01

    Examination of the solute composition and salinities of the lakes where Limnocythere sappaensis and L. staplini live reveals that solute composition and not salinity is the most critical factor that controls their occurrence. L. sappaensis lives in water that is enriched in Na-HCO3-CO3 and depleted in Ca. L. staplini lives in water that is enriched in various combinations of Na-Mg-Ca-SO4-Cl and is depleted in HCO3. These taxa may be used as reliable paleohydrochemical indicators. -from Author

  14. Exact Solution of a Faraday's Law Problem that Includes a Nonlinear Term and Its Implication for Perturbation Theory.

    ERIC Educational Resources Information Center

    Fulcher, Lewis P.

    1979-01-01

    Presents an exact solution to the nonlinear Faraday's law problem of a rod sliding on frictionless rails with resistance. Compares the results with perturbation calculations based on the methods of Poisson and Pincare and of Kryloff and Bogoliuboff. (Author/GA)

  15. Implications of Stream Gains and Losses for Hydrologic Turnover and Solute Retention/Transport at the Stream Network Scale

    NASA Astrophysics Data System (ADS)

    Covino, T. P.; McGlynn, B. L.; Mallard, J.

    2010-12-01

    The exchange of water between streams and groundwater can influence streamwater quality, hydrologic mass balances, and attenuate solute export from watersheds. We used conservative tracer injections (chloride, Cl-) across 10 stream reaches to investigate streamwater gains and losses at larger spatial and temporal scales than typically associated with hyporheic exchanges. We found strong relationships between reach discharge, median tracer velocity, and gross hydrologic loss across a broad range of stream types and sizes in the 11.7 km2 Bull Trout Watershed of central ID. We used these empirical relationships to constrain a network model that simulates streamwater gains and losses and subsequent fractional hydrologic turnover across the stream network. We found that variable gains and losses can influence solute signatures across stream networks and lead to increasing dissolved solute concentration inertia moving downstream. These results also elucidate the proportional influence and distance support to stream discharge and solute signatures from runoff generation locations across the stream network and can provide insight into the internal mechanisms that partially control the hydrologic and biogeochemical signals observed at watershed outlets.

  16. Coupled dissolution and precipitation at the cerussite-phosphate solution interface: implications for immobilization of lead in soils.

    PubMed

    Wang, Lijun; Putnis, Christine V; Ruiz-Agudo, Encarnación; King, Helen E; Putnis, Andrew

    2013-01-01

    In situ atomic force microscopy (AFM) has been used to study the interaction of phosphate-bearing solutions with cerussite, PbCO3, (010) surfaces. During the dissolution of cerussite we observed simultaneous growth of needle-shaped or spherical pyromorphite phases. This occurred at two different pH values and ionic strengths relevant to soil solution conditions. The initial dissolution processes occurring at the cerussite solid-phosphate solution interface were clearly distinguished, and heterogeneous nucleation and growth rates of pyromorphites at phosphate concentrations ranging from 0.1 μM to 10 mM were quantitatively defined. Enhanced cerussite dissolution in the presence of high salt (NaCl or NaF) concentrations leads to an increase in pyromorphite nucleation and growth rates. The newly formed pyromorphites were found to be stable upon contact with water or citrate-bearing solutions under acidic or alkaline conditions in the pH range 4-8. These in situ observations may improve the mechanistic understanding of processes resulting in lead immobilization in diverse soil systems as well as to enhance the effectiveness of phosphate-based treatments for remediation of lead-polluted soils.

  17. Water activity and mobility in solutions of glycerol and small molecular weight sugars: Implication for cryo- and lyopreservation

    NASA Astrophysics Data System (ADS)

    He, Xiaoming; Fowler, Alex; Toner, Mehmet

    2006-10-01

    In this study, the free volume models, originally developed for large molecular weight polymer-solvent systems, were used to study the water activity and mobility in solutions of four small molecular weight cryo-/lyoprotectants, viz., glycerol, a monosaccharide (fructose), and two disaccharides (sucrose and trehalose). The free volume model parameters were determined by fitting the models to available experimental data using a nonlinear optimization procedure. It was found that free volume models could accurately predict the available experimental data, which suggests that the free volume models might be generally applicable to aqueous solutions of small molecular weight cryo-/lyoprotectants. Furthermore, several models for estimating the mutual diffusion coefficient were tested using available experimental data for aqueous solutions of glycerol and a better method to estimate the mutual diffusion coefficient was proposed. Free volume models were used to predict and analyze the water activity and mobility in solutions of four cryo-/lyoprotectants under conditions frequently encountered in cryo-/lyopreservation applications. It was found that the water mobility in the glassy state of the above four solutions is essentially negligible in the case of cryopreservation with storage temperature lower than -110°C. However, the water mobility in a glass at higher temperature (>-80°C) may be significant. As a result, a subcooling of up to 50°C may be necessary for the long-term cryo-/lyopreservation of biomaterials depending on the water content and the type of cryo-/lyoprotectants. It was further shown that trehalose might be the best of the four protectants studied for lyopreservation (water mass fraction ⩽0.1) when the storage temperature is above the room temperature. The results from this study might be useful for the development of more effective protocols for both cryopreservation and lyopreservation of living cells and other biomaterials.

  18. Albumin oxidation leads to neutrophil activation in vitro and inaccurate measurement of serum albumin in patients with diabetic nephropathy.

    PubMed

    Michelis, Regina; Kristal, Batya; Zeitun, Teuta; Shapiro, Galina; Fridman, Yoav; Geron, Ronit; Sela, Shifra

    2013-07-01

    Previous studies suggest that oxidative modifications of serum albumin lead to underestimation of albumin concentrations using conventional assays. In addition, oxidation of serum albumin may cause neutrophil activation and further oxidation of albumin, which may result in a series of reciprocal cyclical processes. Because hypoalbuminemia, systemic inflammation, and oxidative stress are common in diabetic nephropathy patients, the aim of this study was to show that albumin modifications and neutrophil activation underlie these reciprocal systemic processes. Blood samples from a cohort of 19 patients with diabetic nephropathy and 15 healthy controls were used for albumin separation. An oxidation-dependent "albumin detection index," representing the detection efficacy of the universal bromocresol green assay, was determined for each subject. This index was correlated with serum albumin levels, various markers of oxidative stress or inflammation, and kidney function. Activation of separated neutrophils by glycoxidized albumin was assessed by the release of neutrophil gelatinase-associated lipocalin (NGAL) and myeloperoxidase (MPO). The albumin detection index of diabetic nephropathy patients was significantly lower compared to that of controls, correlating positively with serum levels of albumin and kidney function and negatively with albumin glycoxidation and inflammatory markers. Glycoxidized albumin had a direct role in neutrophil activation, resulting in NGAL and MPO release. The hypoalbuminemia observed in patients with diabetic nephropathy partially results from underestimation of modified/oxidized albumin using the bromocresol green assay. However, modified or oxidized albumin may lead to a cycle of accelerated oxidative stress and inflammation involving neutrophil activation. We suggest that the albumin detection index, a new marker of oxidative stress, may also serve as a biomarker of diabetic nephropathy severity and its progression.

  19. Lack of a synergistic effect of arginine-glutamic acid on the physical stability of spray-dried bovine serum albumin.

    PubMed

    Reslan, Mouhamad; Demir, Yusuf K; Trout, Bernhardt L; Chan, Hak-Kim; Kayser, Veysel

    2017-09-01

    Improving the physical stability of spray-dried proteins is essential for enabling pulmonary delivery of biotherapeutics as a noninvasive alternative to injections. Recently, a novel combination of two amino acids - l-arginine (l-Arg) and l-glutamic acid (l-Glu), has been reported to have synergistic protein-stabilizing effects on various protein solutions. Using spray-dried bovine serum albumin (BSA) reconstituted in solution as a model protein, we investigated the synergistic effect of these amino acids on the physical stability of proteins. Five BSA solutions were prepared: (1) BSA with no amino acids (control); (2) with 50 mM l-Arg; (3) with 200 mM l-Arg, (4) with 50 mM l-Glu and (5) with 25:25 mM of Arg:Glu. All solutions were spray-dried and accelerated studies at high temperatures were performed. Following accelerated studies, monomer BSA loss was measured using SE-HPLC. We found that l-Arg significantly improved the physical stability of spray-dried BSA even at low concentrations, however, when combined with l-Glu, was ineffective at reducing monomer BSA loss. Our findings demonstrate the limitations in using Arg-Glu for the stabilization of spray-dried BSA. Furthermore, we found that a low concentration of l-Glu enhanced monomer BSA loss. These findings may have significant implications on the design of future biotherapeutic formulations.

  20. Hydrophobic conjugated microporous polymers for sorption of human serum albumin

    NASA Astrophysics Data System (ADS)

    Zheng, Chunli; Du, Miaomiao; Feng, Shanshan; Sun, Hanxue; Li, An; He, Chi; Zhang, TianCheng; Wang, Qiaorui; Wei, Wei

    2016-02-01

    This paper investigated the sorption of human serum albumin (HSA) from water by three kinds of conjugated microporous polymers (CMPs) with surface hydrophobicity and intrinsic porosity. It was found that the three CMPs captured HSA with fast sorption kinetics and good working capacity. Equilibrium was obtained at 80 min for all the tests, and the maximum sorption quantity (qm) ranged from 0.07 to 0.14 mg/mg. With the increase in the particle external surface area of the CMPs, a greater extent of HSA sorption was achieved. Moreover, promoting the dispersion of CMPs in HSA aqueous solution was also beneficial to the extraction. Attenuated Total Reflection Fourier Transform Infrared spectroscopy verified the interactions between the CMPs and the Nsbnd H, Cdbnd O, and Csbnd N groups of HSA. This paper might provide fundamental guidance for the practical application of CMPs to proteins separation and recovery.

  1. Spectroscopic investigation of interaction between mangiferin and bovine serum albumin

    NASA Astrophysics Data System (ADS)

    Lin, Hui; Lan, Jingfeng; Guan, Min; Sheng, Fenling; Zhang, Haixia

    2009-09-01

    The mechanism of interaction between mangiferin (MA) and bovine serum albumin (BSA) in aqueous solution was investigated by fluorescence spectra, synchronous fluorescence spectra, absorbance spectra and Fourier transform infrared (FT-IR) spectroscopy. The binding constants and binding sites of MA to BSA at different reaction times were calculated. And the distance between MA and BSA was estimated to be 5.20 nm based on Föster's theory. In addition, synchronous fluorescence and FT-IR measurements revealed that the secondary structures of the protein changed after the interaction of MA with BSA. As a conclusion, the interaction between the anti-diabetes Chinese medicine MA and BSA may provide some significant information for the mechanism of the traditional chinese medicine MA on the protein level to cure diabetes or other diseases.

  2. Production of Molecular Iodine and Tri-iodide in the Frozen Solution of Iodide: Implication for Polar Atmosphere.

    PubMed

    Kim, Kitae; Yabushita, Akihiro; Okumura, Masanori; Saiz-Lopez, Alfonso; Cuevas, Carlos A; Blaszczak-Boxe, Christopher S; Min, Dae Wi; Yoon, Ho-Il; Choi, Wonyong

    2016-02-02

    The chemistry of reactive halogens in the polar atmosphere plays important roles in ozone and mercury depletion events, oxidizing capacity, and dimethylsulfide oxidation to form cloud-condensation nuclei. Among halogen species, the sources and emission mechanisms of inorganic iodine compounds in the polar boundary layer remain unknown. Here, we demonstrate that the production of tri-iodide (I3(-)) via iodide oxidation, which is negligible in aqueous solution, is significantly accelerated in frozen solution, both in the presence and the absence of solar irradiation. Field experiments carried out in the Antarctic region (King George Island, 62°13'S, 58°47'W) also showed that the generation of tri-iodide via solar photo-oxidation was enhanced when iodide was added to various ice media. The emission of gaseous I2 from the irradiated frozen solution of iodide to the gas phase was detected by using cavity ring-down spectroscopy, which was observed both in the frozen state at 253 K and after thawing the ice at 298 K. The accelerated (photo-)oxidation of iodide and the subsequent formation of tri-iodide and I2 in ice appear to be related with the freeze concentration of iodide and dissolved O2 trapped in the ice crystal grain boundaries. We propose that an accelerated abiotic transformation of iodide to gaseous I2 in ice media provides a previously unrecognized formation pathway of active iodine species in the polar atmosphere.

  3. A counter-reductionist argument for the influence of solute composition on ostracode distribution: Implications for paleoecology

    SciTech Connect

    Taylor, L.C.; Howard, K.W.F. )

    1992-01-01

    The utility of fossil ostracodes for tracking climatically-driven Holocene physicochemical changes of lakes has been a recurrent theme in paleoenvironmental research. Recent studies, aimed at improving the precision of ostracode-mediated environmental reconstructions, have attempted to decipher this robust, ostracode-climate, couplet, and strong correlational evidence concerning the influence of solute composition on ostracode distribution has emerged. By drawing on two examples, namely the response of ostracodes to (1) Holocene hydrocompositional changes in a lake from Russell, Manitoba, and (2) the anthropogenic contamination of groundwater along an urban-rural transect in south-central Ontario, a hypothesis is generated to explain this apparent association. Contrary to the reductionist opinions (i.e. that hydrochemistry operates on ostracode distribution through the direct imposition of physiological barriers), solute composition is viewed as a surrogate variable through which to evaluate cumulative, immeasurable effects of climate, geology, hydrology and the biosphere (including humans). By virtue of their short life-cycles, it is suggested that ostracodes would overcome evolutionary barriers imposed by gradual changes in solute composition if it uniquely controlled their occurrence. Solving this problem would enhance the resolving power of paleoenvironmental reconstructions and, if the proposed argument is valid, it may lend credibility to uniformitarian principles operative in Quaternary paleoecology. The replacement of one group of species by another better adapted to an environment in its totality, seems more likely to hold up in ecological time, than adaptation to a single, specific, overriding hydrochemical parameter.

  4. Spatial Connectivity and Temporal Response of Variable Source Areas (VSAs): Implications for Catchment Scale Water and Solute Mixing

    NASA Astrophysics Data System (ADS)

    Inamdar, S.; Mitchell, M.; McDonnell, J.; McGlynn, B.; Shanley, J.

    2001-05-01

    The significance of variable source areas (VSAs) in storm runoff generation and as loci for mixing of event and pre-event waters has long been recognized. Recent research suggests that VSAs may also play an important role in regulating the export of C and N solutes from catchments. We hypothesize that the spatial distribution of VSAs in the catchment and their connectedness with the stream network is a first order control on the temporal dynamics and expression of water and solutes from the catchment. We examined two contrasting scenarios of VSA distribution: (1) VSAs located lower in the catchment and well connected to the stream network, versus, (2) discrete VSAs located in the upper portions of the catchment and disconnected from the stream network. We evaluated the potential impact of these scenarios on: (a) the timing and peak of event water contributions, and (b) the timing and peak of solute signatures. We hypothesized that if VSAs are well connected to the stream network (Scenario 1), then event water contributions would be distinct and would predominate early on during the rising limb of the hydrograph of stream discharge. In contrast, if VSAs are isolated and disconnected (Scenario 2), then event water contributions would be damped and delayed and possibly continue to be observed through hydrograph recession. We believe solutes such as dissolved organic carbon (DOC), which are primarily flushed from near surface soil horizons, will follow an event water trajectory. We tested these hypotheses for a 135 ha forested headwater catchment in the Adirondack Mountains of New York. Detailed storm runoff and solute data for the catchment are available since 1994. A two-component separation model using base cations (Na, Mg, Ca, and K) was used to partition stormflow discharge into pre-event and event components. Event water contributions were small on the rising limb of the hydrograph, reached their maximum just after the discharge peak, and continued through the

  5. Transcytotic passage of albumin through lens epithelial cells.

    PubMed

    Sabah, Judith R; Schultz, Bruce D; Brown, Zach W; Nguyen, Annelise T; Reddan, John; Takemoto, Larry J

    2007-03-01

    To characterize the transcytotic passage of albumin through lens epithelial cells. N/N 1003A rabbit lens epithelial cells were grown to a confluent monolayer on porous filter supports (Transwell Corning, Inc., Corning, NY). Monolayers were exposed apically to Alexa 488-labeled albumin (Alexa 488-BSA) in the absence and presence of endocytic inhibitors (filipin; dansylcadaverine [DCV]). Transcytotic passage of albumin was monitored for 4 hours by quantitating fluorescence in the basolateral compartment. The mechanism of albumin passage was studied by labeling cell monolayers and cryosections of whole rat lenses for clathrin or caveolin. The monolayer of cells formed a barrier to the passage of albumin, as shown by the 44% reduction in albumin passage in comparison to nonseeded membranes. Treatment with filipin or DCV reduced the passage of Alexa 488-BSA through lens epithelial cells by 73% and 66%, respectively. Confocal microscopy showed that albumin passage was predominantly transcellular and demonstrated colocalization of albumin with caveolin-1 and clathrin in lens epithelial and fiber cells. The Transwell apparatus is an excellent system to monitor transport systems across cell monolayers. In this study, rabbit lens epithelial cells formed a confluent monolayer that acted as a barrier to the passive diffusion of albumin. The kinetics of albumin movement across the monolayer and the inhibitor pharmacology suggests that lens cells actively transport albumin from the apical to the basolateral compartment. The inhibitory profile suggests the involvement of caveolae and clathrin-coated vesicles in the transcytotic process.

  6. Interaction of triterpenoids with human serum albumin: A review.

    PubMed

    Abboud, Rola; Charcosset, Catherine; Greige-Gerges, Hélène

    2017-10-01

    Triterpenoids are a large group of natural and synthetic products. This review deals with the current state of knowledge on their interaction with serum albumin. The binding of drugs to albumin may control their distribution in tissues. In literature, different techniques were used to investigate the albumin-triterpenoid interaction and include fluorescence spectroscopy, Fourier transform infrared spectroscopy, circular dichroism, calorimetric techniques and molecular modeling. Changes in fluorescence intensity of albumin were observed upon triterpenoid-albumin complex formation. Thermodynamic analyses proved that hydrophobic interactions and hydrogen bonds were the mainly binding forces in triterpenoid-albumin systems. Molecular docking and site marker competitive experimental results revealed that triterpenoids bound to Sudlow's site I of albumin. Furthermore, Fourier transform infrared spectroscopy and circular dichroism spectra analysis indicated that the native conformation of the protein is affected upon binding to triterpenoids. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Fluorescent holograms with albumin-acrylamide

    NASA Astrophysics Data System (ADS)

    Ordóñez-Padilla, M. J.; Olivares-Pérez, A.; Fuentes-Tapia, I.

    2014-02-01

    We describe fluorescent holograms were made with photosensitive films of albumin (protein) quail, used as modified matrices. Albumin is mixed with acrylamide and eosin Y. Therefore, prepare a photosensitive emulsion and solid hydrated with the ability to phase transmission holograms and volume (VPH). Eosin Y is a fluorescent agent that acts as a photo-sensitizing dye which stimulates the polymerization of acrylamide. To record the interference pattern produced by two waves superimposed on the modified matrix, we use a He-Cd laser. To reconstruct the diffraction pattern is observed with He- Ne laser, λ = 632.8nm, the material is self-developing properties. Measure the diffraction efficiency of the diffracted orders (η[-1, +1]) as a function of exposure energy. We work with various thicknesses and measure the variation of the refractive index using the coupled wave theory of Kogelnik, the holographic gratings meet Bragg condition.

  8. A Dual Electrochemical Sensor Based on a Test-strip Assay for the Quantitative Determination of Albumin and Creatinine.

    PubMed

    Yasukawa, Tomoyuki; Kiba, Yuya; Mizutani, Fumio

    2015-01-01

    A dual-electrochemical sensor based on a test-strip assay with immunochemistry and enzyme reactions has been developed for the determination of albumin and creatinine. Each nitrocellulose membrane with an immobilization area of an anti-albumin antibody or three enzymes was prepared in the device with three working electrodes for measuring albumin, creatinine, and ascorbic acid, as well as an Ag/AgCl electrode used as a counter/pseudo-reference electrode. The reactions of three enzymes were initiated by flowing a solution containing creatinine to detect an oxidation current of hydrogen peroxide. A sandwich-type immunocomplex was formed by albumin and antibody labeled with glucose oxidase (GOx). Captured GOx catalyzed the reduction of Fe(CN)6(3-) to Fe(CN)6(4-), which was oxidized electrochemically to determine the captured albumin. The responses for creatinine and albumin increased with the concentrations in millimolar order and over the range 18.75 - 150 μg mL(-1), respectively. The present sensor would be a distinct demonstration for producing quantitative dual-assays for various biomolecules used for clinical diagnoses.

  9. (PCG) Protein Crystal Growth Horse Serum Albumin

    NASA Technical Reports Server (NTRS)

    1995-01-01

    Horse Serum Albumin crystals grown during the USML-1 (STS-50) mission's Protein Crystal Growth Glovebox Experiment. These crystals were grown using a vapor diffusion technique at 22 degrees C. The crystals were allowed to grow for nine days while in orbit. Crystals of 1.0 mm in length were produced. The most abundant blood serum protein, regulates blood pressure and transports ions, metabolites, and therapeutic drugs. Principal Investigator was Edward Meehan.

  10. (PCG) Protein Crystal Growth Horse Serum Albumin

    NASA Technical Reports Server (NTRS)

    1995-01-01

    Horse Serum Albumin crystals grown during the USML-1 (STS-50) mission's Protein Crystal Growth Glovebox Experiment. These crystals were grown using a vapor diffusion technique at 22 degrees C. The crystals were allowed to grow for nine days while in orbit. Crystals of 1.0 mm in length were produced. The most abundant blood serum protein, regulates blood pressure and transports ions, metabolites, and therapeutic drugs. Principal Investigator was Edward Meehan.

  11. (PCG) Protein Crystal Growth Human Serum Albumin

    NASA Technical Reports Server (NTRS)

    1989-01-01

    (PCG) Protein Crystal Growth Human Serum Albumin. Contributes to many transport and regulatory processes and has multifunctional binding properties which range from various metals, to fatty acids, hormones, and a wide spectrum of therapeutic drugs. The most abundant protein of the circulatory system. It binds and transports an incredible variety of biological and pharmaceutical ligands throughout the blood stream. Principal Investigator on STS-26 was Larry DeLucas.

  12. Universal fractal scaling in stream chemistry and its implications for solute transport and water quality trend detection.

    PubMed

    Kirchner, James W; Neal, Colin

    2013-07-23

    The chemical dynamics of lakes and streams affect their suitability as aquatic habitats and as water supplies for human needs. Because water quality is typically monitored only weekly or monthly, however, the higher-frequency dynamics of stream chemistry have remained largely invisible. To illuminate a wider spectrum of water quality dynamics, rainfall and streamflow were sampled in two headwater catchments at Plynlimon, Wales, at 7-h intervals for 1-2 y and weekly for over two decades, and were analyzed for 45 solutes spanning the periodic table from H(+) to U. Here we show that in streamflow, all 45 of these solutes, including nutrients, trace elements, and toxic metals, exhibit fractal 1/f(α) scaling on time scales from hours to decades (α = 1.05 ± 0.15, mean ± SD). We show that this fractal scaling can arise through dispersion of random chemical inputs distributed across a catchment. These 1/f time series are non-self-averaging: monthly, yearly, or decadal averages are approximately as variable, one from the next, as individual measurements taken hours or days apart, defying naive statistical expectations. (By contrast, stream discharge itself is nonfractal, and self-averaging on time scales of months and longer.) In the solute time series, statistically significant trends arise much more frequently, on all time scales, than one would expect from conventional t statistics. However, these same trends are poor predictors of future trends-much poorer than one would expect from their calculated uncertainties. Our results illustrate how 1/f time series pose fundamental challenges to trend analysis and change detection in environmental systems.

  13. Universal fractal scaling in stream chemistry and its implications for solute transport and water quality trend detection

    PubMed Central

    Kirchner, James W.; Neal, Colin

    2013-01-01

    The chemical dynamics of lakes and streams affect their suitability as aquatic habitats and as water supplies for human needs. Because water quality is typically monitored only weekly or monthly, however, the higher-frequency dynamics of stream chemistry have remained largely invisible. To illuminate a wider spectrum of water quality dynamics, rainfall and streamflow were sampled in two headwater catchments at Plynlimon, Wales, at 7-h intervals for 1–2 y and weekly for over two decades, and were analyzed for 45 solutes spanning the periodic table from H+ to U. Here we show that in streamflow, all 45 of these solutes, including nutrients, trace elements, and toxic metals, exhibit fractal 1/fα scaling on time scales from hours to decades (α = 1.05 ± 0.15, mean ± SD). We show that this fractal scaling can arise through dispersion of random chemical inputs distributed across a catchment. These 1/f time series are non–self-averaging: monthly, yearly, or decadal averages are approximately as variable, one from the next, as individual measurements taken hours or days apart, defying naive statistical expectations. (By contrast, stream discharge itself is nonfractal, and self-averaging on time scales of months and longer.) In the solute time series, statistically significant trends arise much more frequently, on all time scales, than one would expect from conventional t statistics. However, these same trends are poor predictors of future trends—much poorer than one would expect from their calculated uncertainties. Our results illustrate how 1/f time series pose fundamental challenges to trend analysis and change detection in environmental systems. PMID:23842090

  14. [Albumin and artificial colloids for massive bleeding].

    PubMed

    Iijima, Takehiko

    2011-01-01

    Rapid and massive bleeding has to be counteracted by efficient volume restoration against rapid loss of intravascular volume. There are two phases of volume management for massive bleeding, uncontrolled phase and controlled phase. During initial uncontrolled phase, rapid infusion of crystalloid with RCC (red cell concentrate) is the first choice of volume management to prevent shock and profound decline of hemoglobin level. After shifting to the next controlled phase, artificial colloids and RCC become the next choice for efficient volume restoration. Although albumin has not been proven to improve prognosis in clinical studies, anti-inflammatory effect could be expected. Albumin infusion may be followed in this phase, and also albumin concentrate may be beneficial to reduce subsequent tissue edema due to massive infusion of crystalloid and artificial colloid. A new generation of hydroxyethyl starch is a promising blood substitute, designed with minimum side effect. Although renal damage especially in septic patient and coagulation disorder are theoretically suspected, beneficial effect as volume expansion overwhelms these stochastic side effects. Since the side effect depends on the dose and how much it remains in the body, a purposeful use during volume expansion phase should be recommended.

  15. Pyrogen reactions to human serum albumin during plasma exchange.

    PubMed

    Pool, M; McLeod, B C

    1995-01-01

    Reactions to human serum albumin (HSA) in therapeutic plasma exchange (TPE) are rare. Nevertheless, older literature describes possible adverse effects, including specific immune responses to albumin or other proteins, and reactions due to contaminating organisms or pyrogen. During an eight day period three patients in our unit had unusual reactions after infusion of 1.5-2 L of HSA. Patient 1 had trembling that persisted for 20 min. Patient 2 had shaking for 40 min despite calcium gluconate infusion, and fever to 100.8 degrees F. Patient 3 had severe rigors that subsided after 90 min when meperidine was finally given, and fever to 103.5 degrees F. Record reviews revealed that all three patients had received HSA from the same lot, and that only one other TPE patient had received HSA from that lot. Neither our pharmacy nor the manufacturer was aware of other reactions associated with that lot. Material from a bottle only partially infused to patient 3 was negative in culture and was negative for pyrogen when retested by the manufacturer. Nevertheless, because patients 1 and 2 had each had multiple previous uneventful TPEs and because all three patients tolerated subsequent TPEs without incident when another brand of HSA was used, we conclude that these patients had pyrogen reactions to the implicated HSA lot. This experience illustrates the value of cluster recognition in arousing suspicion of unusual reactions to HSA and the value of recorded lot numbers in pursuing such suspicions. Apheresis personnel should be aware of the potential for pyrogen reactions with HSA and should record lot numbers of all fluids infused during TPE.

  16. Urinary clearance of albumin is critically determined by its tertiary structure.

    PubMed

    Clavant, Steven P; Comper, Wayne D

    2003-12-01

    The excretion of serum albumin in the urine is considered the net result of renal glomerular filtration and tubular uptake. During routine experiments, we observed that a batch of tritium-labeled albumin yielded anomalous results, being excreted in the urine of isolated perfused kidneys at 10 times the rate of normal tritiated albumin. This anomalous albumin, when simultaneously studied with normal carbon 14-labeled albumin, exhibited 10 times greater excretion than normal [(14)C]albumin. Anomalous albumin could not be reversed to normal albumin by means of conditioning with blood. In vivo clearances of anomalous albumin could not be quantitated because anomalous albumin is degraded during circulation. Anomalous albumin appeared to have the same molecular size (as determined with sodium dodecyl sulfate-polyacrylamide gel electrophoresis, capillary electrophoresis, and gel chromatography) and isoelectric-point profile (2-dimensional electrophresis) as normal albumin. Normal albumin could be transformed to anomalous albumin with alkali/heat treatment. Reverse-phase high-pressure liquid chromatography analysis of fragments from tryptic digests of anomalous albumin, alkali/heat-treated albumin, and normal albumin suggest that anomalous albumin and alkali/heat-treated albumin have altered tertiary structure, possibly as a result of denaturation and disulfide exchange. These studies show that the tertiary structure of albumin, beyond simple size and charge, is a critical determinant for albumin processing by the kidney and suggest that a specific albumin-recognition event by the kidneys is critical to normal renal handling of albumin.

  17. Differential modulation in binding of ketoprofen to bovine serum albumin in the presence and absence of surfactants: spectroscopic and calorimetric insights.

    PubMed

    Misra, Pinaki P; Kishore, Nand

    2013-07-01

    Surfactants have long been implicated in the unique static and dynamic effect on the structure and function of serum albumins. However, there is very little information on the mode of interactions of drugs to serum albumins in presence of surfactants. The importance of such studies lay in the fact that apart from binding to serum albumins, surfactants are known to radically influence the solvents' micro environment and protein structure. Thus, we have studied the binding of the racemic form of ketoprofen with bovine serum albumin at pH 7.4 in the presence and absence of hexadecyl trimethyl ammonium bromide, sodium dodecyl sulfate, Triton X-100, and NaCl. The structural studies of ketoprofen with bovine serum albumin as investigated by circular dichroism spectroscopy revealed a significant stabilization of bovine serum albumin. However, the combined presence of the surfactants, NaCl and ketoprofen, demonstrated an extremely erratic behavior in terms of stabilization. Further the values of Stern-Volmer and dynamic quenching constant suggested the binding site of ketoprofen to be scattered in the region of domain I B and II A, close to Trp 134. The results of differential scanning calorimetry revealed that the binding of ketoprofen to bovine serum albumin leads to its temperature-dependent separation into two units. The binding parameters of bovine serum albumin obtained from isothermal titration calorimetry in the combined presence of ketoprofen and surfactants/NaCl correlate well with the differential scanning calorimetry studies further confirming the localization of ketoprofen in domain I B and II A. In the combined presence of surfactants, NaCl and ketoprofen, the binding of ketoprofen to bovine serum albumin exhibited altered binding parameters far different from the binding of ketoprofen alone. Overall, the experimental findings strongly indicated positive as well as negative modulation in the binding of ketoprofen to bovine serum albumin in the presence of

  18. Binding of aluminum to human serum transferrin, human serum albumin and rat serum proteins

    SciTech Connect

    El-Sebae, A.K.H.; Zeid, M.M.A.; Abdel-Rahman, F.H.; Saleh, M.A. . Environmental Chemistry and Toxicology Lab.)

    1994-01-01

    Human serum transferrin (HSTF), human serum albumin (HSA) and rat serum were compared for their interaction with AlCl[sub 3], in a Tris-HCl buffer solutions. The AlCl[sub 3] was tested in series of concentrations in the range of 50 [mu]M up to 500 [mu]M. HSTF, HSA and their 1:1 mixture and rat serum were incubated at 37 C with series of AlCl[sub 3] concentrations. The protein profile of the incubated solutions were compared to control using SDS-PAGE and FPLC tests. The results indicated that HSTF was more specifically responsive to AlCl[sub 3] showing a characteristic increase in it UV absorption, peak and area dimensions. Simultaneously, HSA was less affected, but it showed a significant shift with an increase in molecular weight accompanied with a change in its profile. The respective bands of transferrin and albumin in rat serum behaved similarly.

  19. Preparation of Tc-99m-macroaggregated albumin from recombinant human albumin for lung perfusion imaging.

    PubMed

    Hunt, A P; Frier, M; Johnson, R A; Berezenko, S; Perkins, A C

    2006-01-01

    Human serum albumin (HSA) extracted from pooled blood taken from human donors is used in the production of (99m)Tc-labelled macroaggregated albumin (MAA) for lung perfusion imaging. However, concerns for the safety of blood-derived products due to potential contamination by infective agents (e.g. new variant CJD), make alternative production methods necessary. Recombinant DNA technology is a promising method of albumin production avoiding problems associated with human-derived HSA. This paper presents results comparing MAA prepared from recombinant human albumin (rHA, Recombumin) (rMAA) with in-house produced HSA MAA (hMAA) and commercially available MAA (cMAA). (99m)Tc-MAA was prepared using previously published production methods by heating a mixture of albumin and stannous chloride in acetate buffer (pH 5.4) at 70 degrees C for 20 min. Parameters investigated include aggregate size, radiolabelling efficiency, radiochemical and aggregate stability at 4 degrees C and in vitro (in whole human blood) at 37 degrees C and biodistribution studies. Results showed that rMAA could be produced with similar morphology, labelling efficiency and stability to hMAA and cMAA. Our findings confirm that rHA shows significant potential as a direct replacement for HSA in commercially available MAA.

  20. Photoreactions of macrocyclic dyes bound to human serum albumin.

    PubMed

    Davila, J; Harriman, A

    1990-01-01

    The photophysical properties of tetrakis(4-sulfonatophenyl)porphyrin (H2TSPP), its tin (IV) complex (SnTSPP), aluminium(III) trisulfonatophthalocyanine (AIPCS), and the corresponding zinc(II) complex (ZnPCS), have been measured in H2O, D2O, and upon binding to human serum albumin (HSA). The triplet excited states of the various macrocyclic dyes generate singlet molecular oxygen, O2(1 delta g) in high quantum yield upon illumination in O2-saturated solution, even in the presence of HSA. The triplet states also abstract an electron from 4-aminophenol, forming the radical anion of the macrocycle. Quenching rate constants and quantum yields have been measured for the various processes in the presence and absence of HSA. It is found that HSA binds all the dyes at nonspecific sites close to the interface in such a manner that the dyes remain accessible to species residing in the solution phase. Dyes that do not possess axial ligands complexed to the central cation (e.g. H2TSPP, ZnPCS) are able to bind also at a deeper, more specific site on the protein where they are protected from species in solution. Under such conditions, triplet quenching by 4-aminophenol is restricted to long-distance electron tunnelling, for which the rate is relatively slow.

  1. [Preparation of Human Serum Albumin Micro/Nanotubes].

    PubMed

    Jiao, Pei-pei; Guo, Yan-li; Niu, Ai-hua; Kang, Xiao-feng

    2016-01-01

    In this research, protein micro/nanotubes were fabricated by alternate layer-by-layer (LbL) assembly of human serum albumin (HSA) and polyethyleneimine (PEI) into polycarbonate (PC) membranes. The experimental conditions of pH values, ionic strength, the depositions cycles and the diameter of porous membrane were discussed. The morphology and composition of tubes were characterized by scanning electron microscope (SEM), transmission electron microscope (TEM), fourier transform infrared spectroscopy (FTIR) and energy dispersive spectroscopy (EDS). The results show that pH and ionic strength of the solution are the key factors that influence the effect of assembly. Micro/nanotubes with good opening hollow tubular structure were obtained when pH 7.4 HSA solution and pH 10.3 PEI solution without NaCl were used in synthesis procedure. The outer diameter of tube was dependent on the PC template, thus the micro/nanotubes size was controlled by the wall thickness, which can be adjusted by the number of layers of the HSA and PEI deposited along the pore walls. To avoid the thin wall being damaged in dissolving the template and vacuum drying, the PEI/HSA bilayer number should not be less than 3. The polar solvent N,N-dimethylformamide (DMF) can dissolve PC template to release the micro/nanotubes.

  2. Superhydrophobic Effect on the Adsorption of Human Serum Albumin

    PubMed Central

    Leibner, Evan S.; Barnthip, Naris; Chen, Weinan; Baumrucker, Craig R.; Badding, John V.; Pishko, Michael; Vogler, Erwin A.

    2009-01-01

    Analytical protocol greatly influences measurement of human-serum albumin (HSA) adsorption to commercial expanded polytetrafluororethylene (ePTFE) exhibiting superhydrophobic wetting properties. Degassing of buffer solutions and evacuation of ePTFE adsorbent to remove trapped air immediately prior to contact with protein solutions are shown to be essential. Results obtained with ePTFE as a prototypical superhydrophobic test material suggest that vacuum degassing should be applied in the measurement of protein adsorption to any surface exhibiting superhydrophobicity. Solution depletion quantified using radiometry (I-125 labeled HSA) or electrophoresis yield different measures of adsorption, with nearly four-fold higher surface concentrations of unlabeled HSA measured by the electrophoresis method. This outcome is attributed to the influence of the radiolabel on HSA hydrophilicity which decreases radiolabeled-HSA affinity for a hydrophobic adsorbent in comparison to unlabeled HSA. These results indicate that radiometry underestimates the actual amount of protein adsorbed to a particular material. Removal of radiolabeled HSA adsorbed to ePTFE by 3X serial buffer rinses also shows that the remaining “bound fraction” was about 35% lower than the amount measured by radiometric depletion. This observation implies that measurement of protein bound after surface rinsing significantly underestimates the actual amount of protein concentrated by adsorption into the surface region of a protein-contacting material. PMID:19135420

  3. Complexation of bovine serum albumin and sugar beet pectin: stabilising oil-in-water emulsions.

    PubMed

    Li, Xiangyang; Fang, Yapeng; Al-Assaf, Saphwan; Phillips, Glyn O; Jiang, Fatang

    2012-12-15

    In a previous study (Langmuir 28 (2012) 10164-10176.), we investigated the complexation of bovine serum albumin (BSA) with sugar beet pectin (SBP). A pH-composition phase diagram was established and structural transitions in relation to the phase diagram during complexation were identified. The present study examines the implications of these interactions on the emulsifying performance of BSA/SBP mixtures. Middle-chain triglycerides (MCTs) in water emulsions were prepared using conditions corresponding to different regions of the phase diagram. At high pHs and in the stable region of mixed individual soluble polymers where complexation is absent, there is no improved emulsifying performance, compared with the individual protein and polysaccharide. For these mixtures, the emulsion characteristics are controlled by the major component in the solutions, as determined by the competitive adsorption of the two components at the oil-water interface. At low pHs and low BSA/SBP ratios, and so mainly within the stable region of intramolecular soluble complexes, BSA/SBP mixtures greatly improve the stability of emulsions. Here, stabilisation is controlled by the cooperative adsorption of the two components at the oil-water interface. Through electrostatic complexation BSA promotes the adsorption of SBP on to interfaces to form a thick steric layer around emulsion droplets and thus providing better stability. At low pHs and high BSA/SBP ratios, that is, mainly within the unstable region of intermolecular insoluble complexes, emulsions prepared are extremely unstable due to bridging flocculation between emulsion droplets.

  4. Albumin and glycated albumin activate KIM-1 release in tubular epithelial cells through distinct kinetics and mechanisms.

    PubMed

    Lim, Ai Ing; Chan, Loretta Y Y; Tang, Sydney C W; Lai, Kar Neng; Leung, Joseph C K

    2014-10-01

    Kidney injury molecule-1 (KIM-1) serves as a useful marker for monitoring tubular injury, and sustained KIM-1 expression may be implicated in chronic kidney fibrosis. In this study, we examine the kinetics and mechanisms of KIM-1 release in human proximal tubular epithelial cells (PTEC) under the activation by major pathologic players in diabetic nephropathy, including human serum albumin (HSA), glycated albumin (AGE-BSA) and high glucose. The kinetics of KIM-1 release by PTEC under activation with HSA, AGE-BSA and high glucose, were determined by RT-PCR and ELISA. The activation profiles of major signaling pathways in PTEC were identified by PCR array. Based on the array data, blockade experiments were designed to assess their regulatory roles in KIM-1 release. Prompt shedding of KIM-1 was observed in PTEC cultured for 4 h with HSA and AGE-BSA, but not with high glucose. Culturing PTEC for 3 days with AGE-BSA exhibited sustained up-regulation of KIM-1 release, but not with HSA. In all culture experiments, high glucose did not induce KIM-1 release in PTEC. HSA and AGE-BSA activated multiple signaling pathways in PTEC including NFκB, ERK1/2 and the oxidative stress pathways. Long-term culturing PTEC with AGE-BSA but not HSA activated the Jak-Stat pathway. While incubation of PTEC with diphenylene iodonium blocked the short-term release of KIM-1 mediated by HSA or AGE-BSA, Jak-Stat inhibitors diminished the long-term KIM-1 release by PTEC induced by AGE-BSA. KIM-1 release in PTEC was differentially up-regulated by HSA and AGE-BSA. The short-term KIM-1 shedding was mediated by the reactive oxygen species, whereas Jak-Stat pathway regulates the long-term KIM-1 release.

  5. Solute hydrogen and hydride phase implications on the plasticity of zirconium and titanium alloys: a review and some recent advances

    NASA Astrophysics Data System (ADS)

    Conforto, E.; Guillot, I.; Feaugas, X.

    2017-06-01

    In this contribution, we propose a review of the possible implications of hydrogen on mechanical behaviour of Zr and Ti alloys with emphasis on the mechanisms of plasticity and strain hardening. Recent advances on the impact of oxygen and hydrogen on the activation volume show that oxygen content hinders creep but hydrogen partially screens this effect. Both aspects are discussed in terms of a locking-unlocking model of the screw dislocation mobility in prismatic slip. Additionally, possible extension of this behaviour is suggested for the slip. The low hydrogen solubility in both Zr and Ti leads in many cases to hydride precipitation. The nature of these phases depends on the hydrogen content and can show crystallographic orientation relationships with the hexagonal compact structure of the alloys. Some advances on the thermal stability of these phases are illustrated and discussed in relation with the deepening of the misfit dislocations. Under tensile loading, we showed that hydrides enhance the hardening process in relation with internal stress due to strain incompatibilities between the Zr and Ti matrix and hydride phases. Different plastic yielding processes of hydrides were identified, which progressively reduce these strain incompatibilities. This article is part of the themed issue 'The challenges of hydrogen and metals'.

  6. Viscosity of supercooled aqueous glycerol solutions, validity of the Stokes-Einstein relationship, and implications for cryopreservation.

    PubMed

    Trejo González, José A; Longinotti, M Paula; Corti, Horacio R

    2012-10-01

    The viscosity of supercooled glycerol aqueous solutions, with glycerol mass fractions between 0.70 and 0.90, have been determined to confirm that the Avramov-Milchev equation describes very well the temperature dependence of the viscosity of the binary mixtures including the supercooled regime. On the contrary, it is shown that the free volume model of viscosity, with the parameters proposed in a recent work (He, Fowler, Toner, J. Appl. Phys. 100 (2006) 074702), overestimates the viscosity of the glycerol-rich mixtures at low temperatures by several orders of magnitude. Moreover, the free volume model for the water diffusion leads to predictions of the Stokes-Einstein product, which are incompatible with the experimental findings. We conclude that the use of these free volume models, with parameters obtained by fitting experimental data far from the supercooled and glassy regions, lead to incorrect predictions of the deterioration rates of biomolecules, overestimating their life times in these cryopreservation media.

  7. An Analytical Solution for Depletion-induced Principal Stress Rotations In 3D and its Implications for Fault Stability

    NASA Astrophysics Data System (ADS)

    Jin, L.; Zoback, M. D.

    2015-12-01

    Depletion-induced faulting in hydrocarbon reservoirs has mostly been attributed to poroelastic effects: in-situ stresses are coupled with a pore pressure change according to a stress path. As a result, for a fault of certain orientation, the shear stress and normal stress resolved on the fault increase in a manner such that the stress state exceeds the shear failure envelop. An underlying assumption associated with this mechanism is that homogeneous pore pressure depletion occurs on both sides of the fault. This study addresses an additional mechanism for depletion-induced faulting in cases where the pore pressure reduction is bounded by a hydraulically impermeable fault. We assume that the overburden and shear stresses are decoupled from pore pressure, while the two horizontal principal stresses are coupled with pore pressure by their respective stress paths (we show that the poroelastic coupling effect is anisotropic). Unbalanced pore pressure changes on the two sides of the fault, in conjunction with the poroelastic response, cause redistribution of the stress state. Given a fault that is arbitrarily oriented with respect to the original stress field, we derive a generalized 3D analytical solution for the new state of stress after depletion. We then quantify the magnitude change and the rotation of the three principal stresses. Finally, we compare the corresponding Coulomb Failure Functions and Mohr circles before and after depletion. For demonstration purposes, we determine the stress path tensor using poroelastic plane strain solutions in conjunction with frictional equilibrium for three different stress regimes. Our hypothetical case studies show that, for bounded reservoirs, depletion-induced principal stress rotation and magnitude changes have a significant impact on fault stability, and are a complex function of fault orientation, the original in-situ stress state and pore pressure, the degree of depletion, and the degree of poroelastic coupling.

  8. Binding of volatile anesthetics to serum albumin: measurements of enthalpy and solvent contributions.

    PubMed

    Sawas, Abdul H; Pentyala, Srinivas N; Rebecchi, Mario J

    2004-10-05

    This study directly examines the enthalpic contributions to binding in aqueous solution of closely related anesthetic haloethers (desflurane, isoflurane, enflurane, and sevoflurane), a haloalkane (halothane), and an intravenous anesthetic (propofol) to bovine and human serum albumin (BSA and HSA) using isothermal titration calorimetry. Binding to serum albumin is exothermic, yielding enthalpies (DeltaH(obs)) of -3 to -6 kcal/mol for BSA with a rank order of apparent equilibrium association constants (K(a) values): desflurane > isoflurane approximately enflurane > halothane >or= sevoflurane, with the differences being largely ascribed to entropic contributions. Competition experiments indicate that volatile anesthetics, at low concentrations, share the same sites in albumin previously identified in crystallographic and photo-cross-linking studies. The magnitude of the observed DeltaH increased linearly with increased reaction temperature, reflecting negative changes in heat capacities (DeltaC(p)). These -DeltaC(p) values significantly exceed those calculated for burial of each anesthetic in a hydrophobic pocket. The enhanced stabilities of the albumin/anesthetic complexes and -DeltaC(p) are consistent with favorable solvent rearrangements that promote binding. This idea is supported by substitution of D(2)O for H(2)O that significantly reduces the favorable binding enthalpy observed for desflurane and isoflurane, with an opposing increase of DeltaS(obs). From these results, we infer that solvent restructuring, resulting from release of water weakly bound to anesthetic and anesthetic-binding sites, is a dominant and favorable contributor to the enthalpy and entropy of binding to proteins.

  9. Laser structuring of carbon nanotubes in the albumin matrix for the creation of composite biostructures.

    PubMed

    Gerasimenko, Alexander Yu; Glukhova, Olga E; Savostyanov, Georgy V; Podgaetsky, Vitaly M

    2017-06-01

    This paper presents the composite biostructures created by laser structuring of the single-walled carbon nanotubes (SWCNTs) in an albumin matrix. Under the exposure of femtosecond laser radiation, the heating of the albumin aqueous solution causes liquid water to evaporate. As a result, we obtained a solid-state composite in the bulk or film form. Using the molecular dynamic method, we showed the formation of a framework from SWCNTs by the example of splicing of the open end of one nanotube with the defect region of another nanotube under the action of the laser heating. Laser heating of SWCNTs up to a temperature of 80°C to 100°C causes the C ? C bond formation. Raman spectra measured for the composite biostructures allowed us to describe the binding of oxygen atoms of amino acid residues of the albumin with the carbon atoms of the SWCNTs. It is found that the interaction energy of the nanotube atoms and albumin atoms amounts up to 580 ?? kJ / mol . We used atomic force microscopy to investigate the surface of the composite biostructures. The pore size is in the range of 30 to 120 nm. It is proved that the proliferation of the fibroblasts occurred on the surface of the composite biostructures during 72 h of incubation.

  10. Determination of the distribution of selenium between selenoprotein P, glutathione peroxidase and albumin in plasma

    SciTech Connect

    Whanger, P.D.; Butler, J.A.; Deagen, J.T. )

    1991-03-11

    A chromatographic method was developed to determine the distribution of selenium between selenoprotein P, glutathione peroxidase (GSH-Px) and albumin, using two small columns of heparin-Sepharose CL-6B (white) and Reactive Blue 2-Sepharose CL-6B (blue) linked together in tandem. One ml of plasma was diluted to 10 ml with 0.02 M sodium phosphate buffer, pH 7.0, the equilibration buffer, and applied to the white column. This was eluted at flow rate of 30 ml per hour. GSHp-Px was not retained by either column but selenoprotein P was retained by the white column and albumin by the blue column. After the two columns were separated, selenoprotein P was eluted for 90 min from the white column with a solution containing 500 units of heparin per ml. The albumin was eluted for 55 min from the blue column with 1.4 M NaCl. This method indicated that over 50% of the selenium in plasma from rats, monkeys, humans and sheep was with selenoprotein P, even during deficiency. From 15 to 22% of the selenium was associated with GSH-Px. The percentage of selenium with albumin was dependent upon the selenomethionine content of the diet.

  11. Investigation of competitive binding of ibuprofen and salicylic acid with serum albumin by affinity capillary electrophoresis.

    PubMed

    Li, Zhu-Mei; Wei, Chuan-Wan; Zhang, Yintang; Wang, Di-Shan; Liu, You-Nian

    2011-07-01

    Ibuprofen and salicylic acid, two typical non-steroidal anti-inflammatory drugs, are used commonly as analgesic drug in clinical medicine and sometimes are co-administered. When the drugs are co-administered, the drug-drug interactions may occur, and can lead to alter the safety and efficacy of drugs, resulting in variations in drug response of the co-administered drugs. Affinity capillary electrophoresis (ACE) was employed to investigate the competitive binding of ibuprofen and salicylic acid on serum albumin. Mobility ratio, derivatives from mobility shift method, was used to deduce the binding constant (K(b)). The binding constants of ibuprofen with HSA are 2.97×10⁶ M⁻¹ and 7.07×10⁴ M⁻¹, respectively; while for salicylic acid, the binding constant is 5.99×10⁴ M⁻¹. The competitive binding of the two drugs was investigated by addition of excessive ibuprofen into the solutions containing constant concentrations of salicylic acid and serum albumin. The results confirmed that ibuprofen and salicylic acid have different high-affinity binding site, but share some low-affinity binding sites on the serum albumin; and ibuprofen is able to partially replace salicylic acid from the preformed binary complexes of serum albumin and salicylic acid. Copyright © 2011 Elsevier B.V. All rights reserved.

  12. Laser structuring of carbon nanotubes in the albumin matrix for the creation of composite biostructures

    NASA Astrophysics Data System (ADS)

    Gerasimenko, Alexander Yu.; Glukhova, Olga E.; Savostyanov, Georgy V.; Podgaetsky, Vitaly M.

    2017-06-01

    This paper presents the composite biostructures created by laser structuring of the single-walled carbon nanotubes (SWCNTs) in an albumin matrix. Under the exposure of femtosecond laser radiation, the heating of the albumin aqueous solution causes liquid water to evaporate. As a result, we obtained a solid-state composite in the bulk or film form. Using the molecular dynamic method, we showed the formation of a framework from SWCNTs by the example of splicing of the open end of one nanotube with the defect region of another nanotube under the action of the laser heating. Laser heating of SWCNTs up to a temperature of 80°C to 100°C causes the C-C bond formation. Raman spectra measured for the composite biostructures allowed us to describe the binding of oxygen atoms of amino acid residues of the albumin with the carbon atoms of the SWCNTs. It is found that the interaction energy of the nanotube atoms and albumin atoms amounts up to 580 kJ/mol. We used atomic force microscopy to investigate the surface of the composite biostructures. The pore size is in the range of 30 to 120 nm. It is proved that the proliferation of the fibroblasts occurred on the surface of the composite biostructures during 72 h of incubation.

  13. Influence of oxygen, albumin and pH on copper dissolution in a simulated uterine fluid.

    PubMed

    Bastidas, D M; Cano, E; Mora, E M

    2005-06-01

    The aim of this paper is to study the influence of albumin content, from 5 to 45 g/L, on copper dissolution and compounds composition in a simulated uterine solution. Experiments were performed in atmospheric pressure conditions and with an additional oxygen pressure of 0.2 atmospheres, at 6.3 and 8.0 pH values, and at a temperature of 37 +/- 0.1 degrees C for 1, 3, 7, and 30 days experimentation time. The copper dissolution rate has been determined using absorbance measurements, finding the highest value for pH 8.0, 35 g/L albumin, and with an additional oxygen pressure of 0.2 atmospheres: 674 microg/day for 1 day, and 301 microg/day for 30 days. X-ray photoelectron spectroscopy (XPS) results show copper(II) as the main copper oxidation state at pH 8.0; and copper(I) and metallic copper at pH 6.3. The presence of albumin up to 35 g/L, accelerates copper dissolution. For high albumin content a stabilisation on the copper dissolution takes place. Corrosion product layer morphology is poorly protective, showing paths through which copper ions can release.

  14. Preparation and characterization of novel biocompatible cryogels of poly (vinyl alcohol) and egg-albumin and their water sorption study.

    PubMed

    Bajpai, A K; Saini, Rajesh

    2006-01-01

    Polyvinyl alcohol (PVA) and egg albumin are water-soluble, biocompatible and biodegradable polymers and have been widely employed in biomedical fields. In this paper, novel physically cross-linked hydrogels composed of poly (vinyl alcohol) and egg albumin were prepared by cyclic freezing/thawing processes of aqueous solutions containing PVA and egg albumin. The FTIR analysis of prepared cryogels indicated that egg albumin was successfully introduced into the formed hydrogel possibly via hydrogen bonds among hydroxyl groups, amide groups and amino groups present in PVA and egg albumin. The gels were also characterized thermally and morphologically by DSC and SEM-techniques, respectively. The prepared so called 'cryogels' were evaluated for their water uptake potential and influence of various factors such as chemical architecture of the spongy hydrogels, pH and temperature of the swelling bath were investigated on the degree of water sorption by the cryogels. The effect of salt solution and various simulated biological fluids on the swelling of cryogel was also studied. The in vitro biocompatibility of the prepared cryogel was also judged by methods such as protein (BSA) adsorption, blood clot formation and percentage hemolysis measurements.

  15. A structurally driven analysis of thiol reactivity in mammalian albumins.

    PubMed

    Spiga, Ottavia; Summa, Domenico; Cirri, Simone; Bernini, Andrea; Venditti, Vincenzo; De Chiara, Matteo; Priora, Raffaella; Frosali, Simona; Margaritis, Antonios; Di Giuseppe, Danila; Di Simplicio, Paolo; Niccolai, Neri

    2011-04-01

    Understanding the structural basis of protein redox activity is still an open question. Hence, by using a structural genomics approach, different albumins have been chosen to correlate protein structural features with the corresponding reaction rates of thiol exchange between albumin and disulfide DTNB. Predicted structures of rat, porcine, and bovine albumins have been compared with the experimentally derived human albumin. High structural similarity among these four albumins can be observed, in spite of their markedly different reactivity with DTNB. Sequence alignments offered preliminary hints on the contributions of sequence-specific local environments modulating albumin reactivity. Molecular dynamics simulations performed on experimental and predicted albumin structures reveal that thiolation rates are influenced by hydrogen bonding pattern and stability of the acceptor C34 sulphur atom with donor groups of nearby residues. Atom depth evolution of albumin C34 thiol groups has been monitored during Molecular Dynamic trajectories. The most reactive albumins appeared also the ones presenting the C34 sulphur atom on the protein surface with the highest accessibility. High C34 sulphur atom reactivity in rat and porcine albumins seems to be determined by the presence of additional positively charged amino acid residues favoring both the C34 S⁻ form and the approach of DTNB.

  16. Can biofuels be a solution to climate change? The implications of land use change-related emissions for policy

    PubMed Central

    Khanna, Madhu; Crago, Christine L.; Black, Mairi

    2011-01-01

    Biofuels have gained increasing attention as an alternative to fossil fuels for several reasons, one of which is their potential to reduce the greenhouse gas (GHG) emissions from the transportation sector. Recent studies have questioned the validity of claims about the potential of biofuels to reduce GHG emissions relative to the liquid fossil fuels they are replacing when emissions owing to direct (DLUC) and indirect land use changes (ILUC) that accompany biofuels are included in the life cycle GHG intensity of biofuels. Studies estimate that the GHG emissions released from ILUC could more than offset the direct GHG savings by producing biofuels and replacing liquid fossil fuels and create a ‘carbon debt’ with a long payback period. The estimates of this payback period, however, vary widely across biofuels from different feedstocks and even for a single biofuel across different modelling assumptions. In the case of corn ethanol, this payback period is found to range from 15 to 200 years. We discuss the challenges in estimating the ILUC effect of a biofuel and differences across biofuels, and its sensitivity to the assumptions and policy scenarios considered by different economic models. We also discuss the implications of ILUC for designing policies that promote biofuels and seek to reduce GHG emissions. In a first-best setting, a global carbon tax is needed to set both DLUC and ILUC emissions to their optimal levels. However, it is unclear whether unilateral GHG mitigation policies, even if they penalize the ILUC-related emissions, would increase social welfare and lead to optimal emission levels. In the absence of a global carbon tax, incentivizing sustainable land use practices through certification standards, government regulations and market-based pressures may be a viable option for reducing ILUC. PMID:22482030

  17. Can biofuels be a solution to climate change? The implications of land use change-related emissions for policy.

    PubMed

    Khanna, Madhu; Crago, Christine L; Black, Mairi

    2011-04-06

    Biofuels have gained increasing attention as an alternative to fossil fuels for several reasons, one of which is their potential to reduce the greenhouse gas (GHG) emissions from the transportation sector. Recent studies have questioned the validity of claims about the potential of biofuels to reduce GHG emissions relative to the liquid fossil fuels they are replacing when emissions owing to direct (DLUC) and indirect land use changes (ILUC) that accompany biofuels are included in the life cycle GHG intensity of biofuels. Studies estimate that the GHG emissions released from ILUC could more than offset the direct GHG savings by producing biofuels and replacing liquid fossil fuels and create a 'carbon debt' with a long payback period. The estimates of this payback period, however, vary widely across biofuels from different feedstocks and even for a single biofuel across different modelling assumptions. In the case of corn ethanol, this payback period is found to range from 15 to 200 years. We discuss the challenges in estimating the ILUC effect of a biofuel and differences across biofuels, and its sensitivity to the assumptions and policy scenarios considered by different economic models. We also discuss the implications of ILUC for designing policies that promote biofuels and seek to reduce GHG emissions. In a first-best setting, a global carbon tax is needed to set both DLUC and ILUC emissions to their optimal levels. However, it is unclear whether unilateral GHG mitigation policies, even if they penalize the ILUC-related emissions, would increase social welfare and lead to optimal emission levels. In the absence of a global carbon tax, incentivizing sustainable land use practices through certification standards, government regulations and market-based pressures may be a viable option for reducing ILUC.

  18. Experimental investigation and planetary implications of the stability of clathrate hydrates in aqueous solution at icy satellite conditions

    NASA Astrophysics Data System (ADS)

    Dunham, M.; Choukroun, M.; Barmatz, M.; Hodyss, R. P.; Smythe, W. D.

    2012-12-01

    Clathrate hydrates consist of hydrogen-bonded water molecules forming cages in which gas molecules are trapped individually. They are among the favored volatile reservoirs in solar system bodies, and are expected to play an important role in many processes: accretion of volatiles in planetesimals, outgassing on Titan, Enceladus, and comets. Their insulating thermal properties and high mechanical strength also bear important implications for understanding the evolution of icy satellites like Europa. However, the conditions allowing for their formation and/or their dissociation and the release of volatiles to the atmosphere (Titan) or the plumes (Enceladus) are still poorly understood. This is mainly because of a lack of knowledge on the stability of mixed clathrate hydrates in presence of anti-freeze agents such as ammonia. We have developed a high-pressure cryogenic calorimeter to address this deficiency in the literature. This liquid nitrogen - cooled Setaram BT2.15 calorimeter is located at the JPL Ice Physics Laboratory. The temperature range achievable with this instrument is 77-473 K. This calorimeter uses Calvet elements (3D arrays of thermocouples) to measure the heat flow required to follow a predefined heating rate within a sample and a reference cell with a resolution of 0.1 μW. A gas handling system has been designed and fabricated in house to reach pressures up to 100 bars, corresponding to several km depth in icy satellites. The thermodynamic properties of CO2 and CH4 clathrates with ammonia are under investigation, and the results will be used to constrain a statistical thermodynamic model of clathrates for applications to planetary environments. Preliminary results will be shown at the meeting. This work has been conducted at the Jet Propulsion Laboratory, California Institute of Technology, under contract to NASA. Support from the Minnesota Space Grant Consortium, the NASA Outer Planets Research program, and government sponsorship are gratefully

  19. Investigation of Cu(II) Binding to Bovine Serum Albumin by Potentiometry with an Ion Selective Electrode

    ERIC Educational Resources Information Center

    Jie Liu

    2004-01-01

    A laboratory project that investigates Cu(II) bind to bovine serum albumin (BSA) in an aqueous solution is developed to assist undergraduate students in gaining better understanding of the interaction of ligands with biological macromolecule. Thus, students are introduced to investigation of Cu(II) binding to BSA by potentiometry with the Cu(II)…

  20. Investigation of Cu(II) Binding to Bovine Serum Albumin by Potentiometry with an Ion Selective Electrode

    ERIC Educational Resources Information Center

    Jie Liu

    2004-01-01

    A laboratory project that investigates Cu(II) bind to bovine serum albumin (BSA) in an aqueous solution is developed to assist undergraduate students in gaining better understanding of the interaction of ligands with biological macromolecule. Thus, students are introduced to investigation of Cu(II) binding to BSA by potentiometry with the Cu(II)…

  1. Properties of CO2 clathrate hydrates formed in the presence of MgSO4 solutions with implications for icy moons

    NASA Astrophysics Data System (ADS)

    Safi, E.; Thompson, S. P.; Evans, A.; Day, S. J.; Murray, C. A.; Parker, J. E.; Baker, A. R.; Oliveira, J. M.; van Loon, J. Th.

    2017-04-01

    Context. There is evidence to suggest that clathrate hydrates have a significant effect on the surface geology of icy bodies in the solar system. However the aqueous environments believed to be present on these bodies are likely to be saline rather than pure water. Laboratory work to underpin the properties of clathrate hydrates in such environments is generally lacking. Aims: We aim to fill this gap by carrying out a laboratory investigation of the physical properties of CO2 clathrate hydrates produced in weak aqueous solutions of MgSO4. Methods: We use in situ synchrotron X-ray powder diffraction to investigate clathrate hydrates formed at high CO2 pressure in ice that has formed from aqueous solutions of MgSO4 with varying concentrations. We measure the thermal expansion, density and dissociation properties of the clathrates under temperature conditions similar to those on icy solar system bodies. Results: We find that the sulphate solution inhibits the formation of clathrates by lowering their dissociation temperatures. Hysteresis is found in the thermal expansion coefficients as the clathrates are cooled and heated; we attribute this to the presence of the salt in solution. We find the density derived from X-ray powder diffraction measurements is temperature and pressure dependent. When comparing the density of the CO2 clathrates to that of the solution in which they were formed, we conclude that they should sink in the oceans in which they form. We also find that the polymorph of ice present at low temperatures is Ih rather than the expected Ic, which we tentatively attribute to the presence of the MgSO4. Conclusions: We (1) conclude that the density of the clathrates has implications for their behaviour in satellite oceans as their sinking and floating capabilities are temperature and pressure dependent; (2) conclude that the presence of MgSO4 inhibits the formation of clathrates and in some cases may even affect their structure and (3) report the dominance

  2. Extreme hemodilution with PEG-hemoglobin vs. PEG-albumin.

    PubMed

    Cabrales, Pedro; Tsai, Amy G; Winslow, Robert M; Intaglietta, Marcos

    2005-12-01

    Isovolemic hemodilution to 11% systemic hematocrit was performed in the hamster window chamber model using 6% dextran 70 kDa (Dx 70) and 5% human serum albumin (HSA). Systemic and microvascular effects of these solutions were compared with polyethylene glycol (PEG)-conjugated 5% albumin (MPA) and PEG-conjugated 4.2% Hb (MP4). These studies were performed for the purpose of comparing systemic and microvascular responses of PEG vs. non-PEG plasma expanders and similar oxygen-carrying vs. noncarrying blood replacement fluids. Mean arterial blood pressure was statistically significantly reduced for all groups compared with baseline (P < 0.05), HSA, MPA, and MP4 higher than Dx 70 (P < 0.05). MP4 and MPA had a significantly higher cardiac index than HSA and Dx 70, in addition to a positive base excess. Microvascular blood flow and capillary perfusion were significantly higher for the PEG compounds compared with HSA and Dx 70. Intravascular PO2 for MP4 and MPA was higher in arterioles (P < 0.05) compared with HSA and Dx 70, but there was no difference in either tissue or venular PO2 between groups. Total Hb in the MP4 group was 4.8 +/- 0.4 g/dl, whereas the remaining groups had a range of 3.6-3.8 g/dl. The hemodilution results showed that PEG compounds maintained microvascular conditions with lower concentrations than conventional plasma expanders. Furthermore, microvascular oxygen delivery and extraction in the window chamber tissue were significantly higher for the PEG compounds. MP4 was significantly higher than MPA (P < 0.05) and was not statistically different from baseline, an effect due to the additional oxygen release to the tissue by the Hb MP4.

  3. Biogenic and synthetic polyamines bind bovine serum albumin.

    PubMed

    Dubeau, S; Bourassa, P; Thomas, T J; Tajmir-Riahi, H A

    2010-06-14

    Biogenic polyamines are found to modulate protein synthesis at different levels, while polyamine analogues have shown major antitumor activity in multiple experimental models, including breast cancer. The aim of this study was to examine the interaction of bovine serum albumin (BSA) with biogenic polyamines, spermine and spermidine, and polyamine analogues 3,7,11,15-tetrazaheptadecane x 4 HCl (BE-333) and 3,7,11,15,19-pentazahenicosane x 5 HCl (BE-3333) in aqueous solution at physiological conditions. FTIR, UV-visible, CD, and fluorescence spectroscopic methods were used to determine the polyamine binding mode and the effects of polyamine complexation on protein stability and secondary structure. Structural analysis showed that polyamines bind BSA via both hydrophilic and hydrophobic interactions. Stronger polyamine-protein complexes formed with biogenic than synthetic polyamines with overall binding constants of K(spm) = 3.56 (+/-0.5) x 10(5) M(-1), K(spmd) = 1.77 (+/-0.4) x 10(5) M(-1), K(BE-333) = 1.11 (+/-0.3) x 10(4) M(-1) and K(BE-3333) = 3.90 (+/-0.7) x 10(4) M(-1) that correlate with their positively charged amino group contents. Major alterations of protein conformation were observed with reduction of alpha-helix from 63% (free protein) to 55-33% and increase of turn 12% (free protein) to 28-16% and random coil from 6% (free protein) to 24-17% in the polyamine-BSA complexes, indicating a partial protein unfolding. These data suggest that serum albumins might act as polyamine carrier proteins in delivering polyamine analogues to target tissues.

  4. Self-assembly behaviour of colistin and its prodrug colistin methanesulfonate: implications for solution stability and solubilization

    PubMed Central

    Wallace, Stephanie J.; Li, Jian; Nation, Roger L.; Prankerd, Richard J.; Velkov, Tony; Boyd, Ben J.

    2010-01-01

    Colistin is an amphiphilic antibiotic that has re-emerged into clinical use due to the increasing prevalence of difficult-to-treat Gram-negative infections. The existence of self-assembling colloids in solutions of colistin and its derivative prodrug, colistin methanesulfonate (CMS) was investigated. Colistin and CMS reduced the air-water interfacial tension, and dynamic light scattering (DLS) studies showed the existence of 2.07 ± 0.3 nm aggregates above 1.5 mM for colistin, and of 1.98 ± 0.36 nm aggregates for CMS above 3.5 mM (mean ± SD). Above the respective critical micelle concentrations (CMC) the solubility of azithromycin, a hydrophobic antibiotic, increased approximately linearly with increasing surfactant concentration (5:1 mol ratio colistin:azithromycin), suggestive of hydrophobic domains within the micellar cores. Rapid conversion of CMS to colistin occurred below the CMC (60 % over 48 hr), while conversion above the CMC was less than 1 %. The formation of colistin and CMS micelles demonstrated in this study is the proposed mechanism for solubilization of azithromycin and the concentration-dependent stability of CMS. PMID:20302384

  5. Routes of drug delivery into the nail apparatus: Implications for the efficacy of topical nail solutions in onychomycosis.

    PubMed

    Gupta, Aditya K; Simpson, Fiona C

    2016-01-01

    The route of antifungal drug entry into the nail plate and the underlying nail bed plays an important role in determining the efficacy of therapy. Oral antifungal agents reach the nail bed and nail plate by being ingested and achieving antifungal levels in the blood stream that are well in excess of the minimum inhibitory concentration. The reticular circulation at the distal end of the digit enables the drug to reach the nail bed, the proximal matrix and the lateral nail folds. The drug then diffuses into the proximal, ventral and lateral nail plate. The primary route of drug delivery for topical lacquers is transungual, with drug applied to the dorsal aspect of the nail plate and penetrating to the underlying nail bed. The new topical agents approved in the US for the treatment of onychomycosis are solutions with lower viscosity and increased nail penetration characteristics; therefore, these agents penetrate through the transungual route, but also through the space between the nail plate and the nail bed. This subungual route is an important method of drug delivery and is able to in part circumvent the thickness of the nail plate.

  6. Isotopic geochemistry of the Saratoga springs: Implications for the origin of solutes and source of carbon dioxide

    NASA Astrophysics Data System (ADS)

    Siegel, Donald I.; Lesniak, Keri A.; Stute, Martin; Frape, Shaun

    2004-03-01

    We report the results of an isotopic study designed to determine the source of solutes and carbon dioxide in the famed Saratoga Springs (New York) mineral waters. These waters have thousands of milligrams per liter total dissolved solid concentrations and are highly charged with carbon dioxide gas. The spring waters are cold (˜12 °C) and there is no local, deep-seated thermal anomaly. They emerge through thick shale caprock along the surface expression of normal faults. The δ13C (-5.8‰ to +0.8‰ Vienna Peedee belemnite) of the dissolved inorganic carbon and elevated 3He/4He ratios suggest that the source of the CO2 is the mantle or an ancient deep crystallized igneous melt. The stable isotopic content of the spring waters defines a mixing line between modern local meteoric waters (δ ˜ 70‰) and a component with heavier δD but similar δ18O values. This trend and that of 87Sr/86Sr of dissolved strontium versus 1/Sr are consistent with the hypothesis that Canadian Shield type brines contribute salinity to the springs. These brines plausibly migrate from the Adirondack Mountains to the topographically low McGregor fault system in the Hudson River lowlands, where the Saratoga springs discharge.

  7. SAM-II Riboswitch Samples at least Two Conformations in Solution in the Absence of Ligand: Implications for Recognition.

    PubMed

    Chen, Bin; LeBlanc, Regan; Dayie, T Kwaku

    2016-02-18

    Conformational equilibria are increasingly recognized as pivotal for biological function. Traditional structural analyses provide a static image of conformers in solution that sometimes present conflicting views. From (13) C and (1) H chemical exchange saturation transfer experiments, in concert with ligation and selective labeling strategies, we show that in the absence of metabolite, a Mg(2+) (0-0.5 mm)-bound apo SAM-II riboswitch RNA exists in a minor (≈10 %) partially closed state that rapidly exchanges with a predominantly (≈90 %) open form with a lifetime of ≈32 ms. The base and sugar (H6,C6, H1',C1') chemical shifts of C43 for the dominant conformer are similar to those of a free CMP, but those of the minor apo species are comparable to shifts of CMPs in helical RNA regions. Our results suggest that these transient, low populated states stabilized by Mg(2+) will likely enhance rapid ligand recognition and, we anticipate, will play potentially ubiquitous roles in RNA signaling. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. African American Participation in Oncology Clinical Trials--Focus on Prostate Cancer: Implications, Barriers, and Potential Solutions.

    PubMed

    Ahaghotu, Chiledum; Tyler, Robert; Sartor, Oliver

    2016-04-01

    In the United States, the incidence and mortality rates of many cancers, especially prostate cancer, are disproportionately high among African American men compared with Caucasian men. Recently, mortality rates for prostate cancer have declined more rapidly in African American versus Caucasian men, but prostate cancer is still the most common cancer and the second leading cause of cancer deaths in African American men in the United States. Compared with Caucasian men, prostate cancer occurs at younger ages, has a higher stage at diagnosis, and is more likely to progress after definitive treatments in African American men. Reasons for racial discrepancies in cancer are multifactorial and potentially include socioeconomic, cultural, nutritional, and biologic elements. In addition to improving access to novel therapies, clinical trial participation is essential to adequately establish the risks and benefits of treatments in African American populations. Considering the disproportionately high mortality rates noted in these groups, our understanding of the natural history and responses to therapies is limited. This review will explore African American underrepresentation in clinical trials with a focus on prostate cancer, and potentially effective strategies to engage African American communities in prostate cancer research. Solutions targeting physicians, investigators, the community, and health care systems are identified. Improvement of African American participation in prostate cancer clinical trials will benefit all stakeholders.

  9. Cu(II) Bis(thiosemicarbazone) Radiopharmaceutical Binding to Serum Albumin: Further Definition of Species-Dependence and Associated Substituent Effects

    PubMed Central

    Basken, Nathan E.; Green, Mark A.

    2009-01-01

    Introduction The Cu-PTSM (pyruvaldehyde bis(N4-methylthiosemicarbazonato)copper(II)) and Cu-ATSM (diacetyl bis(N4-methylthiosemicarbazonato)copper(II)) radiopharmaceuticals exhibit strong, species-dependent binding to the IIA site of human serum albumin (HSA), while the related Cu-ETS (ethylglyoxal bis(thiosemicarbazonato)copper(II)) radiopharmaceutical appears to only exhibit non-specific binding to human and animal serum albumins. Methods To further probe the structural basis for the species-dependence of this albumin binding interaction, protein binding of these three radiopharmaceuticals was examined in solutions of albumin and/or serum from a broader array of mammalian species (rat, sheep, donkey, rabbit, cow, pig, dog, baboon, mouse, cat, elephant). We also evaluated the albumin binding of several copper(II) bis(thiosemicarbazone) chelates offering more diverse substitution of the ligand backbone. Results Cu-PTSM and Cu-ATSM exhibit a strong interaction with HSA that is not apparent with the albumins of other species, while the binding of Cu-ETS to albumin is much less species-dependent. The strong interaction of Cu-PTSM with HSA does not appear to simply correlate with variation, relative to the animal albumins, of a single amino acid lining HSA's IIA site. Those agents that selectively interact with HSA share the common feature of only methyl or hydrogen substitution at the carbon atoms of the diimine fragment of the ligand backbone. Conclusions The interspecies variations in albumin binding of Cu-PTSM and Cu-ATSM are not simply explained by unique amino acid substitutions in the IIA binding pocket of the serum albumins. However, the specific affinity for this region of HSA is disrupted when substituents bulkier than a methyl group appear on the imine carbons of the copper bis(thiosemicarbazone) chelate. PMID:19520290

  10. The combination of octreotide and midodrine is not superior to albumin in preventing recurrence of ascites after large-volume paracentesis.

    PubMed

    Bari, Khurram; Miñano, Cecilia; Shea, Martha; Inayat, Irteza B; Hashem, Hashem J; Gilles, Hochong; Heuman, Douglas; Garcia-Tsao, Guadalupe

    2012-10-01

    Large-volume paracentesis (LVP) is the treatment of choice for patients with cirrhosis and refractory ascites. However, LVP can lead to postparacentesis circulatory dysfunction (PCD), which is associated with faster ascites recurrence and renal failure. PCD results from vasodilatation, which reduces effective blood volume, and is prevented by intravenous administration of albumin. Vasoconstrictors could be used instead of albumin and, with longer use, prevent PCD and delay ascites recurrence. We performed a multicenter, randomized, double-blind, placebo-controlled trial to compare albumin with the vasoconstrictor combination of octreotide and midodrine in patients with refractory ascites who underwent LVP. Patients in the albumin group received a single intravenous dose of albumin at the time of LVP plus placebos for midodrine and octreotide (n = 13). Patients in the vasoconstrictor group received saline solution (as a placebo for albumin), 10 mg of oral midodrine (3 times/day), and a monthly 20-mg intramuscular injection of long-acting octreotide (n = 12). Patients were followed up until recurrence of ascites. The median times to recurrence of ascites were 10 days in the albumin group and 8 days in the vasoconstrictor group (P = .318). There were no significant differences in PCD between the albumin group (18%) and the vasoconstrictor group (25%, P = .574). When ascites recurred, serum levels of creatinine were higher in the vasoconstrictor group (1.2 vs 0.9 mg/dL in the albumin group; P = .051). The combination of midodrine and octreotide after LVP is not superior to albumin in delaying recurrence of ascites or preventing PCD in patients with cirrhosis. Outcomes appear to be worse in patients given octreotide and midodrine. ClinicalTrials.gov number, NCT00108355. Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.

  11. The Combination of Octreotide and Midodrine is not Superior to Albumin in Preventing Recurrence of Ascites after Large-Volume Paracentesis

    PubMed Central

    Bari, Khurram; Minano, Cecilia; Shea, Martha; Inayat, Irteza B.; Hashem, Hashem J.; Gilles, HoChong; Heuman, Douglas; Garcia-Tsao, Guadalupe

    2012-01-01

    Background & Aims Large-volume paracentesis (LVP) is the treatment of choice for patients with cirrhosis and refractory ascites. However, LVP can lead to post-paracentesis circulatory dysfunction (PCD), which is associated with faster ascites recurrence and renal failure. PCD results from vasodilatation, which reduces effective blood volume, and is prevented by intravenous administration of albumin. Vasoconstrictors could be used instead of albumin and, with longer use, prevent PCD and delay ascites recurrence. Methods We performed a multicenter, randomized, double-blind, placebo controlled trial to compare albumin with the vasoconstrictor combination of octreotide and midodrine in patients with refractory ascites who underwent LVP. Patients in the albumin group received a single intravenous dose of albumin at the time of LVP plus placebos for midodrine and octreotide (n=13). Patients in the vasoconstrictor group received saline solution (as a placebo for albumin), 10 mg of oral midodrine (3 times daily), and a monthly, 20 mcg intra-muscular injection of long-acting octreotide (n=12). Patients were followed until recurrence of ascites. Results The median times to recurrence of ascites were 10 days in the albumin group and 8 days in the vasoconstrictor group (P=.318). There were no significant differences in PCD between the albumin group (18%) and the vasoconstrictor group (25%, P=.574). When ascites recurred, serum levels of creatinine were higher in the vasoconstrictor group (1.2 vs 0.9 mg/dL in the albumin group, P=.051). Conclusions The combination of midodrine and octreotide after LVP is not superior to albumin in delaying recurrence of ascites or preventing PCD in patients with cirrhosis. Outcomes appear to be worse in patients given octreotide and midodrine. PMID:22801062

  12. Albumin regeneration in liver support-comparison of different methods.

    PubMed

    Mitzner, Steffen; Klammt, Sebastian; Stange, Jan; Schmidt, Reinhart

    2006-04-01

    Albumin is the most abundant human plasma protein. Among many other functions it is an important transporter of hydrophobic internal and external substances such as intermediate and end products of metabolism and drugs. In liver failure the albumin binding capacity is decreased because of a disproportion between available albumin molecules caused by decreased hepatic synthesis and hydrophobic toxins because of decreased hepatic clearance. The resulting increase in plasma and tissue concentrations of these substances is associated with multiple organ dysfunctions frequently seen in severe liver failure. The scope of the present article is to compare different liver support strategies with regard to their ability to regenerate the patients albumin pool by removing albumin-bound toxins. Most prominent technique in this group is the molecular adsorbent recirculating system (MARS). It will be compared with single pass albumin dialysis (SPAD), fractionated plasma separation and adsorption system (FPSA, Prometheus), and plasma perfusion/bilirubin adsorption with special regard to efficacy and selectivity.

  13. Synthesis and characterization of 2-mercaptoethanesulfonic acid albumin.

    PubMed

    Bauer, H H; Ehmig, S; Engels, J W; Voelcker, G

    1998-06-01

    Autoimmune patients treated with ifosfamide (CAS 3778-73-2) and mesna (2-mercaptoethanesulfonic acid, CAS 3375-50-6) in some cases suffered from severe allergic reactions that were proposed to be due to mesna linked to serum albumin by a disulfide bond. To prove the existence of the hypothetic mesna albumin adduct in vivo it was synthesized: The free thiol group of albumin (molecular mass determined by MALDI spectroscopy: 67009 Da) was converted to S-phenylsulfonyl albumin and reacted with mesna to albumin mesna (molecular mass: 67159 Da). In an alternative synthesis albumin was incubated with mesna at pH 8, 40 degrees C (molecular mass of the adduct: 67166 Da).

  14. Establishment and implications of a characterization method for magnetic nanoparticle using cell tracking velocimetry and magnetic susceptibility modified solutions.

    PubMed

    Zhang, Huading; Moore, Lee R; Zborowski, Maciej; Williams, P Stephen; Margel, Shlomo; Chalmers, Jeffrey J

    2005-04-01

    Magnetic micro and nanoparticles conjugated to affinity labels have become a significant, commercial reagent. It has been demonstrated that the performance of cell separation systems using magnetic labels is a function of the magnitude of the magnetic force that can be generated through labeling. This magnetic force is proportional to the number of magnetic particles bound to the cell, the magnetic energy gradient, and the particle-field interaction parameter. This particle-field interaction parameter, which is the product of the relative volumetric, magnetic susceptibility and the volume of the micro or nanoparticle, is a fundamental parameter which can be used to characterize the magnetic particles. An experimental technique is presented which measures the volumetric magnetic susceptibility of particles through the use of susceptibility modified solutions and an experimental instrument, Cell Tracking Velocimetry, CTV. Experimental studies were conducted on polystyrene microspheres alone and those bound to four different magnetic nanoparticles. The experimentally determined values of the magnetic susceptibility of the polystyrene microspheres are consistent with values found from literature. Consequently, magnetic susceptibility measurements of these polystyrene microspheres bound with the magnetic nanoparticles combined with particle size measurements using commercial dynamic light scattering instrument allowed estimates of the particle-field interaction parameter to be made for four commercial, magnetic nanoparticles. The value found for MACS beads is close to what is reported from an independent study. The values for MACS beads and Imag beads are found to agree with what is observed from experiments. Finally, an experimental demonstration of the impact that differences in this field interaction parameter has on the labeling of human lymphocytes is presented.

  15. Chemical transformation of iodate(IO3-) and nitrite(NO2-) in frozen solution and its environmental implications.

    NASA Astrophysics Data System (ADS)

    Kim, Kitae

    2017-04-01

    Ice is ubiquitous on earth and involved in various chemical reactions in the environment. Most chemical reactions are slowed down when temperature decreases according to Arrhenius equation. However, several chemical processes can be enhanced in frozen state. Reactive halogen species play important roles in the global environment. In particular, the presence of gaseous halogens in the polar and marine boundary layers is of great interest because these highly reactive species can affect ozone and mercury depletion events, oxidizing capacity, and DMS(dimethylsulfide) oxidation to form cloud-condensation nuclei. Among halogen compounds, the sources and emission mechanisms of inorganic iodine species in the polar region remain unclear. Iodide(I-) and iodate(IO3-) are the most dominant iodine species in nature and their chemical transformation or I-/IO3- ratio in frozen state remains poorly understood. Recent study shows that the production of active iodine compounds from frozen iodate salts during photochemical reaction. In previous study, nitrite(NO2-) oxidation to nitrate(NO3-), which is very slow reaction in aqueous solution, was significantly (105 times) accelerated in frozen state. The enhanced proton and oxygen concentration within ice grain boundaries are suspected that the enhanced oxidation of nitrite by freezing. Here we investigate chemical transformation of iodate/nitrite mixture in ice. The results show that the chemical reaction between iodate and nitrite in ice can potentially provide a new pathway for the source of reactive iodine species to the polar atmosphere. The detailed experimental conditions and mechanism will be discussed in the presentation.

  16. [Characteristics of serum albumin in patients with intracerebral hemorrhagic stroke].

    PubMed

    Martynov, M Iu; Koplik, E V; Shchukin, I A; Smolina, N V; Kapel'nitskiĭ, P V; Chubykin, V I; Glukhareva, A P; Makarov, A N; Sudakov, K V

    2012-01-01

    Authors studied the influence of the psychoemotional stress preceding the stroke on the dynamics of neurological symptoms (Glasgo coma scale, Scandinavian stroke scale and Barthel index) and on the conformational changes of albumin in 59 patients with intracerebral hemorrhage due to arterial hypertension. The psychoemotional stress was associated with less favorable clinical course and outcome of intracerebral hemorrhage. Conformational properties of albumin were changed in all patients with intracerebral hemorrhage compared to controls. Psychoemotional stress preceding stroke aggravated changes in albumin molecule.

  17. Transfer of Oleic Acid between Albumin and Phospholipid Vesicles

    NASA Astrophysics Data System (ADS)

    Hamilton, James A.; Cistola, David P.

    1986-01-01

    The net transfer of oleic acid between egg phosphatidylcholine unilamellar vesicles and bovine serum albumin has been monitored by 13C NMR spectroscopy and 90% isotopically substituted [1-13C]oleic acid. The carboxyl chemical shifts of oleic acid bound to albumin were different from those for oleic acid in phospholipid vesicles. Therefore, in mixtures of donor particles (vesicles or albumin with oleic acid) and acceptor particles (fatty acid-free albumin or vesicles), the equilibrium distribution of oleic acid was determined from chemical shift and peak intensity data without separation of donor and acceptor particles. In a system containing equal masses of albumin and phospholipid and a stoichiometry of 4-5 mol of oleic acid per mol of albumin, the oleic acid distribution was pH dependent, with >= 80% of the oleic acid associated with albumin at pH 7.4; association was >= 90% at pH 8.0. Decreasing the pH below 7.4 markedly decreased the proportion of fatty acid bound to albumin; at pH 5.4, <= 10% of the oleic acid was bound to albumin and >90% was associated with vesicles. The distribution was reversible with pH and was independent of whether vesicles or albumin acted as a donor. These data suggest that pH may strongly influence the partitioning of fatty acid between cellular membranes and albumin. The 13C NMR method is also advantageous because it provides information about the structural environments of oleic acid bound to albumin or phospholipid, the ionization state of oleic acid in each environment, and the structural integrity of the vesicles. In addition, minimum and maximum limits for the exchange rates of oleic acid among different environments were obtained from the NMR data.

  18. Development of an albumin copper binding (ACuB) assay to detect ischemia modified albumin.

    PubMed

    Eom, Ji-Eun; Lee, Eunyoung; Jeon, Kyung-Hwa; Sim, Jeongeun; Suh, Minah; Jhon, Gil-Ja; Kwon, Youngjoo

    2014-01-01

    Myocardial ischemia (MI) induces many changes in the body, including pH decrease and electrolyte imbalance. No obvious symptoms of MI appear until irreversible cellular injuries occur. Since early treatment is critical for recovery from ischemia, the development of reliable diagnostic tool is demanded to detect the early ischemic status. Ischemia modified albumin (IMA), formed by cleavage of the last two amino acids of the human serum albumin (HSA) N-terminus, has been considered so far as the most trustworthy and accurate marker for the investigation of ischemia. IMA levels are elevated in plasma within a few minutes of ischemic onset, and may last for up to 6 h. In the present study, we developed a novel assay for the examination of IMA levels to ameliorate the known albumin cobalt binding (ACB) test established previously. We observed a stronger copper ion bound to the HSA N-terminal peptide than cobalt ion by HPLC and ESI-TOF mass spectrometric analyses. The copper ion was employed with lucifer yellow (LY), a copper-specific reagent to develop a new albumin copper binding (ACuB) assay. The parameters capable of affecting the assay results were optimized, and the finally-optimized ACuB assay was validated. The result of the IMA level measurement in normal versus stroke rat serum suggests that the ACuB assay is likely to be a reliable and sensitive method for the detection of ischemic states.

  19. Ligand-dependent conformational equilibria of serum albumin revealed by tryptophan fluorescence quenching.

    PubMed Central

    Chadborn, N; Bryant, J; Bain, A J; O'Shea, P

    1999-01-01

    Ligand-dependent structural changes in serum albumin are suggested to underlie its role in physiological solute transport and receptor-mediated cellular selection. Evidence of ligand-induced (oleic acid) structural changes in serum albumin are shown in both time-resolved and steady-state fluorescence quenching and anisotropy measurements of tryptophan 214 (Trp214). These studies were augmented with column chromatography separations. It was found that both the steady-state and time-resolved Stern-Volmer collisional quenching studies of Trp214 with acrylamide pointed to the existence of an oleate-dependent structural transformation. The bimolecular quenching rate constant of defatted human serum albumin, 1.96 x 10(9) M-1 s-1, decreased to 0.94 x 10(9) M-1 s-1 after incubation with oleic acid (9:1). Furthermore, Stern-Volmer quenching studies following fractionation of the structural forms by hydrophobic interaction chromatography were in accordance with this interpretation. Time-resolved fluorescence anisotropy measurements of the Trp214 residue yielded information of motion within the protein together with the whole protein molecule. Characteristic changes in these motions were observed after the binding of oleate to albumin. The addition of oleate was accompanied by an increase in the rotational diffusion time of the albumin molecule from approximately 22 to 33.6 ns. Within the body of the protein, however, the rotational diffusion time for Trp214 exhibited a slight decrease from 191 to 182 ps and was accompanied by a decrease in the extent of the angular motion of Trp214, indicating a transition after oleate binding to a more spatially restricted but less viscous environment. PMID:10096914

  20. Behavior of drug excited states within macromolecules: binding of colchicine and derivatives to albumin.

    PubMed

    Bosca, Francisco; Tormos, Rosa

    2013-06-27

    The aqueous solutions of colchicine (COL) and analogues such as colchiceine (CEI), and N-deacetylcolchiceine (DCEI) have been studied by laser flash photolysis (LFP) with and without the presence of human serum albumin (HSA) to determine the possible interactions between the drugs and the albumin. When irradiation of these drugs was performed in aqueous media, transient absorption species were not detected. However, triplet excited states of CEI and DCEI were detected when the experiments were carried out in the presence of albumin. Contrary to expectations, in the case of COL, no transient absorption species was observed. A deep study of COL triplet excited-state properties has revealed that intersystem crossing quantum yield (φ(ISC)) decreases from organic media such as dichloromethane to water with φ(ISC) values ca. 0.035 and <0.001 respectively. This fact together the inappreciable reactivity of (3)COL with tyrosine and tryptophan agree with the unbinding of COL to HSA. This study will show for the first time a way to determine the association constant (K(a)) using the LFP technique. Thus, for CEI and DCEI binding to HSA, K(a) values of 8 ± 3 × 10(4) M(-1) and 2 ± 1 × 10(4) M(-1) were obtained, respectively. Moreover, it was also established that these drugs are mainly placed into site II of the albumin using this technique. Therefore, this study validates the LFP as a useful methodology to study the interactions of COL and its analogues with serum albumins, and consequently it could be applied to others proteins such as tubulin.

  1. Interactions of aptamers with sera albumins

    NASA Astrophysics Data System (ADS)

    Cortez, Célia Martins; Silva, Dilson; Silva, Camila M. C.; Missailidis, Sotiris

    2012-09-01

    The interactions of two short aptamers to human and bovine serum albumins were studied by fluorescence spectroscopic techniques. Intrinsic fluorescence of BSA and HSA were measured by selectively exciting their tryptophan residues. Gradual quenching was observed by titration of both proteins with aptamers. Aptamers are oligonucleic acid or peptide molecules that bind a specific target and can be used for both biotechnological and clinical purposes, since they present molecular recognition properties like that commonly found in antibodies. Two aptamers previously selected against the MUC1 tumour marker were used in this study, one selected for the protein core and one for the glycosylated MUC1. Stern-Volmer graphs were plotted and quenching constants were estimated. Plots obtained from experiments carried out at 25 °C and 37 °C showed the quenching of fluorescence of by aptamers to be a collisional phenomenon. Stern-Volmer constants estimated for HSA quenched by aptamer A were 1.68 × 105 (±5 × 103) M-1 at 37 °C, and 1.37 × 105 (±103) M-1 at 25 °C; and quenched by aptamer B were 1.67 × 105 (±5 × 103) M-1 at 37 °C, and 1.32 × 105 (±103) M-1 at 25 °C. Results suggest that the primary binding site for aptamers on albumin is close to tryptophan residues in sub domain IIA.

  2. Preparation of Curcumin Loaded Egg Albumin Nanoparticles Using Acetone and Optimization of Desolvation Process.

    PubMed

    Aniesrani Delfiya, D S; Thangavel, K; Amirtham, D

    2016-04-01

    In this study, acetone was used as a desolvating agent to prepare the curcumin-loaded egg albumin nanoparticles. Response surface methodology was employed to analyze the influence of process parameters namely concentration (5-15%w/v) and pH (5-7) of egg albumin solution on solubility, curcumin loading and entrapment efficiency, nanoparticles yield and particle size. Optimum processing conditions obtained from response surface analysis were found to be the egg albumin solution concentration of 8.85%w/v and pH of 5. At this optimum condition, the solubility of 33.57%, curcumin loading of 4.125%, curcumin entrapment efficiency of 55.23%, yield of 72.85% and particles size of 232.6 nm were obtained and these values were related to the values which are predicted using polynomial model equations. Thus, the model equations generated for each response was validated and it can be used to predict the response values at any concentration and pH.

  3. Bovine serum albumin promotes IL-1beta and TNF-alpha secretion by N9 microglial cells.

    PubMed

    Zhao, Tian-zhi; Xia, Yong-zhi; Li, Lan; Li, Jian; Zhu, Gang; Chen, Shi; Feng, Hua; Lin, Jiang-kai

    2009-10-01

    Bovine serum albumin (BSA) is generally used in biomedical experiments. In the solution of some reagents, BSA is necessary to maintain the stability and concentration of the effective component. Therefore, the potential impact of BSA on experimental results should not be neglected when BSA is used. In this study, we observed that BSA induced significant upregulation of mRNA expression and release of pro-inflammatory cytokines, IL-1beta, and TNF-alpha, by N9 microglial cells. Our results suggest that the effects of BSA should be taken into account in experiments on microglia or the central nervous system when BSA is used. In light of the high similarity and homology among mammalian albumins, our findings also indicate that serum albumin may be a potent trigger of cytokine release by microglia.

  4. Spectral Fluorescence Properties of an Anionic Oxacarbocyanine Dye in Complexes with Human Serum Albumin

    NASA Astrophysics Data System (ADS)

    Pronkin, P. G.; Tatikolov, A. S.

    2015-07-01

    The spectral fluorescence properties of the anionic oxacarbocyanine dye 3,3'-di-(γ-sulfopropyl)-5,5'-diphenyl-9-ethyloxacarbocyanine betaine (OCC) were studied in solutions and in complexes with human serum albumin (HSA). Interaction with HSA leads to a significant increase in the fluorescence of the dye. We studied quenching of the fluorescence of OCC in a complex with HSA by ibuprofen and warfarin. Data on quenching of fluorescence by ibuprofen indicate binding of the dye to binding site II of subdomain IIIA in the HSA molecule. Synchronous fluorescence spectra of human serum albumin in the presence of OCC showed that complexation with OCC does not lead to appreciable rearrangement of the protein molecule at the binding site.

  5. Photodynamic effect occurance in photosensitizer mixtures with albumin or blood serum, or hemoglobin and blood

    NASA Astrophysics Data System (ADS)

    Torshina, Nadezgda L.; Posypanova, Anna M.; Volkova, Anna I.

    1996-05-01

    Under laser irradiation of different photosensitizers (PS) mixtures with pure albumin or without hemolysis blood serum the photodynamic effect (PE) is scarcely to be manifested. The coupling of PS with albumins prevents the interactions of dissolved oxygen molecules with PS molecules and formation of active oxygen forms. In order to promote the PE it is necessary to add the solution of hemoglobin. The PE is readily recognized in mixtures of PS with the blood. Such mixing leads to the erythrocytes' destruction and yields uncombined hemoglobin in blood plasma. The irradiation of hemoglobin mixtures with PS leads to the destruction of hemoglobin. In this case the direct combination of oxygen molecules with hemoglobin is important for PE performance (the deoxy hemoglobin can not promote PE otherwise).

  6. Dialysate with high dissolved hydrogen facilitates dissociation of indoxyl sulfate from albumin.

    PubMed

    Tange, Yoshihiro; Takesawa, Shingo; Yoshitake, Shigenori

    2015-03-01

    Protein-bound toxins such as indoxyl sulfate (IS) are not efficiently removed by conventional hemodialysis (HD). To improve the removal of IS, we performed an in vitro study to evaluate the effects of high dissolved hydrogen on the dissociation of IS from albumin using simulated HD. Wasted dialysate from peritoneal dialysis was concentrated a hundred times using extracorporeal ultrafiltration method. Dialysate with high dissolved hydrogen was made by mixing concentrated dialysis solution and electrolyzed-reduced water. The amounts of free fractions of IS were determined by high performance liquid chromatography. IS was significantly dissociated from albumin using dialysate with high dissolved hydrogen compared with conventional dialysate (P < 0.05). Effective removal of IS is expected using a dialysate with high dissolved hydrogen.

  7. Immobilization of Bovine Serum Albumin Upon Multiwall Carbon Nanotube for High Speed Humidity Sensing Application.

    PubMed

    Bhattacharya, Sankhya; Sasmal, Milan

    2016-01-01

    We present a high-speed humidity sensor based on immobilization of bovine serum albumin upon multiwall carbon nanotube (IBC). A simple and versatile drop casting technique was employed to make the humidity sensor using novel material IBC at room temperature. IBC was synthesized using easy solution process technique. The working principle of the IBC humidity sensor depends upon the variation of output current or conductance with the exposure of different humidity level. Humidity sensing properties of our device is explained on the basis of charge transfer from water molecules to IBC and bovine serum albumin to multiwall carbon nanotube (MWCNT). Our sensor exhibits faster response time around 1.2 s and recovery time 1.5 s respectively.

  8. Reversible exposure of hydrophobic residues on albumin as a novel strategy for formulation of nanodelivery vehicles for taxanes

    PubMed Central

    Garro, AG; Beltramo, DM; Alasino, RV; Leonhard, V; Heredia, V; Bianco, ID

    2011-01-01

    Background: We report herein a novel strategy for the preparation of protein-based nanode-livery vehicles for hydrophobic active pharmaceutical ingredients. Methods: The procedure consisted of three steps, ie, exposure of hydrophobic residues of a protein to a pH-induced partial unfolding: interaction between hydrophobic residues on the protein and the hydrophobic active pharmaceutical ingredient, and a final step where the structure of the protein was reversed to a native-like state by returning to neutral pH. As proof of concept, the interaction of paclitaxel with partially unfolded states of human serum albumin was evaluated as a potential method for the preparation of water-soluble complexes of the taxane with albumin. Results: We found that paclitaxel readily binds to pH-induced partially unfolded albumin, leading to the formation of optically clear water-soluble complexes. The complexes thus formed were more stable in solution when the albumin native state was at least partially restored by neutralization of the solution to a pH around 7. It was also observed that the hydrodynamic radius of human serum albumin was only slightly increased after the cycle of pH changes, remaining in a monomeric state with a size according to paclitaxel binding. Furthermore, paclitaxel binding did not affect the overall exposure of charged groups of human serum albumin, as evaluated by its interaction with an ionic exchange resin. Conclusion: The in vitro biological activity of the complexes formed was qualitatively equivalent to that of a Cremophor®-based formulation. PMID:21822381

  9. Solution structure, domain features, and structural implications of mutants of the chromo domain from the fission yeast histone methyltransferase Clr4.

    PubMed

    Horita, D A; Ivanova, A V; Altieri, A S; Klar, A J; Byrd, R A

    2001-03-30

    The encapsulation of otherwise transcribable loci within transcriptionally inactive heterochromatin is rapidly gaining recognition as an important mechanism of epigenetic gene regulation. In the fission yeast Schizosaccharomyces pombe, heterochromatinization of the mat2/mat3 loci silences the mating-type information encoded within these loci. Here, we present the solution structure of the chromo domain from the cryptic loci regulator protein Clr4. Clr4 is known to regulate silencing and switching at the mating-type loci and to affect chromatin structure at centromeres. Clr4 and its human and Drosophila homologs have been identified as histone H3-specific methyltransferases, further implicating this family of proteins in chromatin remodeling. Our structure highlights a conserved surface that may be involved in chromo domain-ligand interactions. We have also analyzed two chromo domain mutants (W31G and W41G) that previously were shown to affect silencing and switching in full-length Clr4. Both mutants are significantly destabilized relative to wild-type. Copyright 2001 Academic Press.

  10. A kinetic model for beta-amyloid adsorption at the air/solution interface and its implication to the beta-amyloid aggregation process.

    PubMed

    Jiang, Dianlu; Dinh, Kim Lien; Ruthenburg, Travis C; Zhang, Yi; Su, Lei; Land, Donald P; Zhou, Feimeng

    2009-03-12

    At the air/buffer solution interface the kinetics of adsorption of amyloid beta peptide, Abeta(1-42), whose bulk concentration (submicromolar) is more than 2 orders of magnitude lower than that typically used in other in vitro aggregation studies, has been studied using a Langmuir-Blodgett trough. The pressure-time curves exhibit a lag phase, wherein the surface pressure essentially remains at zero, and a rising phase, corresponding to the Abeta adsorption at the interface. The duration of the lag phase was found to be highly dependent on both the Abeta bulk concentration and the solution temperature. A large activation energy (62.2 +/- 4.1 KJ/mol) was determined and the apparent adsorption rate constant was found to be linearly dependent on the Abeta bulk concentration. Attenuated total reflection-IR spectra of the adsorbed Abeta transferred to a solid substrate and circular dichroism measurements of Abeta in the solution layer near the interface reveal that the natively unstructured Abeta in the bulk undergo a conformation change (folding) to mainly the alpha-helical structure. The results suggest that, prior to the adsorption step, an equilibrium between Abeta conformations is established within the subsurface. The kinetic equation derived from this model confirms that the overall Abeta adsorption is kinetically controlled and the apparent rate constant is proportional to the Abeta bulk concentration. This model also indicates that interfaces such as cell membranes and lipid bilayers may facilitate Abeta aggregation/ fibrillation by providing a thin hydrophobic layer adjacent to the interface for the initial A/beta conformation change (misfolding) and accumulation. Such a preconcentration effect offers a plausible explanation of the fact that Abeta fibrillation occurs in vivo at nanomolar concentrations. Another important biological implication from our work is that Abeta misfolding may occur before its adsorption onto a cell membrane. This general kinetic model

  11. Fluorescence dilution technique for measurement of albumin reflection coefficient in isolated glomeruli.

    PubMed

    Fan, Fan; Chen, Chun Cheng Andy; Zhang, Jin; Schreck, Carlos M N; Roman, Eric A; Williams, Jan M; Hirata, Takashi; Sharma, Mukut; Beard, Daniel A; Savin, Virginia J; Roman, Richard J

    2015-12-15

    This study describes a high-throughput fluorescence dilution technique to measure the albumin reflection coefficient (σAlb) of isolated glomeruli. Rats were injected with FITC-dextran 250 (75 mg/kg), and the glomeruli were isolated in a 6% BSA solution. Changes in the fluorescence of the glomerulus due to water influx in response to an imposed oncotic gradient was used to determine σAlb. Adjustment of the albumin concentration of the bath from 6 to 5, 4, 3, and 2% produced a 10, 25, 35, and 50% decrease in the fluorescence of the glomeruli. Pretreatment of glomeruli with protamine sulfate (2 mg/ml) or TGF-β1 (10 ng/ml) decreased σAlb from 1 to 0.54 and 0.48, respectively. Water and solute movement were modeled using Kedem-Katchalsky equations, and the measured responses closely fit the predicted behavior, indicating that loss of albumin by solvent drag or diffusion is negligible compared with the movement of water. We also found that σAlb was reduced by 17% in fawn hooded hypertensive rats, 33% in hypertensive Dahl salt-sensitive (SS) rats, 26% in streptozotocin-treated diabetic Dahl SS rats, and 21% in 6-mo old type II diabetic nephropathy rats relative to control Sprague-Dawley rats. The changes in glomerular permeability to albumin were correlated with the degree of proteinuria in these strains. These findings indicate that the fluorescence dilution technique can be used to measure σAlb in populations of isolated glomeruli and provides a means to assess the development of glomerular injury in hypertensive and diabetic models. Copyright © 2015 the American Physiological Society.

  12. Fluorescence dilution technique for measurement of albumin reflection coefficient in isolated glomeruli

    PubMed Central

    Fan, Fan; Chen, Chun Cheng Andy; Zhang, Jin; Schreck, Carlos M. N.; Williams, Jan M.; Hirata, Takashi; Sharma, Mukut; Beard, Daniel A.; Savin, Virginia J.; Roman, Richard J.

    2015-01-01

    This study describes a high-throughput fluorescence dilution technique to measure the albumin reflection coefficient (σAlb) of isolated glomeruli. Rats were injected with FITC-dextran 250 (75 mg/kg), and the glomeruli were isolated in a 6% BSA solution. Changes in the fluorescence of the glomerulus due to water influx in response to an imposed oncotic gradient was used to determine σAlb. Adjustment of the albumin concentration of the bath from 6 to 5, 4, 3, and 2% produced a 10, 25, 35, and 50% decrease in the fluorescence of the glomeruli. Pretreatment of glomeruli with protamine sulfate (2 mg/ml) or TGF-β1 (10 ng/ml) decreased σAlb from 1 to 0.54 and 0.48, respectively. Water and solute movement were modeled using Kedem-Katchalsky equations, and the measured responses closely fit the predicted behavior, indicating that loss of albumin by solvent drag or diffusion is negligible compared with the movement of water. We also found that σAlb was reduced by 17% in fawn hooded hypertensive rats, 33% in hypertensive Dahl salt-sensitive (SS) rats, 26% in streptozotocin-treated diabetic Dahl SS rats, and 21% in 6-mo old type II diabetic nephropathy rats relative to control Sprague-Dawley rats. The changes in glomerular permeability to albumin were correlated with the degree of proteinuria in these strains. These findings indicate that the fluorescence dilution technique can be used to measure σAlb in populations of isolated glomeruli and provides a means to assess the development of glomerular injury in hypertensive and diabetic models. PMID:26447220

  13. Serum albumin promotes ATP-binding cassette transporter-dependent sterol uptake in yeast.

    PubMed

    Marek, Magdalena; Silvestro, Daniele; Fredslund, Maria D; Andersen, Tonni G; Pomorski, Thomas G

    2014-12-01

    Sterol uptake in fungi is a multistep process that involves interaction between external sterols and the cell wall, incorporation of sterol molecules into the plasma membrane, and subsequent integration into intracellular membranes for turnover. ATP-binding cassette (ABC) transporters have been implicated in sterol uptake, but key features of their activity remain to be elucidated. Here, we apply fluorescent cholesterol (NBD-cholesterol) to monitor sterol uptake under anaerobic and aerobic conditions in two fungal species, Candida glabrata (Cg) and Saccharomyces cerevisiae (Sc). We found that in both fungal species, ABC transporter-dependent uptake of cholesterol under anaerobic conditions and in mutants lacking HEM1 gene is promoted in the presence of the serum protein albumin that is able to bind the sterol molecule. Furthermore, the C. glabrata ABC transporter CgAus1p expressed in S. cerevisiae requires the presence of serum or albumin for efficient cholesterol uptake. These results suggest that albumin can serve as sterol donor in ABC transporter-dependent sterol uptake, a process potentially important for growth of C. glabrata inside infected humans. © 2014 The Authors. FEMS Yeast Research published by John Wiley & Sons Ltd on behalf of Federation of European Microbiological Societies.

  14. Detergents as probes of hydrophobic binding cavities in serum albumin and other water-soluble proteins.

    PubMed Central

    Kragh-Hansen, U; Hellec, F; de Foresta, B; le Maire, M; Møller, J V

    2001-01-01

    As an extension of our studies on the interaction of detergents with membranes and membrane proteins, we have investigated their binding to water-soluble proteins. Anionic aliphatic compounds (dodecanoate and dodecylsulfate) were bound to serum albumin with high affinity at nine sites; related nonionic detergents (C12E8 and dodecylmaltoside) were bound at seven to eight sites, many in common with those of dodecanoate. The compounds were also bound in the hydrophobic cavity of beta-lactoglobulin, but not to ovalbumin. In addition to the generally recognized role of the Sudlow binding region II of serum albumin (localized at the IIIA subdomain) in fatty acid binding, quenching of the fluorescence intensity of tryptophan-214 by 7,8-dibromododecylmaltoside and 12-bromododecanoate also implicate the Sudlow binding region I (subdomain IIA) as a locus for binding of aliphatic compounds. Our data document the usefulness of dodecyl amphipathic compounds as probes of hydrophobic cavities in water-soluble proteins. In conjunction with recent x-ray diffraction analyses of fatty acid binding as the starting point we propose a new symmetrical binding model for the location of nine high-affinity sites on serum albumin for aliphatic compounds. PMID:11371462

  15. Neo-epitopes on methylglyoxal modified human serum albumin lead to aggressive autoimmune response in diabetes.

    PubMed

    Jyoti; Mir, Abdul Rouf; Habib, Safia; Siddiqui, Sheelu Shafiq; Ali, Asif; Moinuddin

    2016-05-01

    Glyco-oxidation of proteins has implications in the progression of diabetes type 2. Human serum albumin is prone to glyco-oxidative attack by sugars and methylglyoxal being a strong glycating agent may have severe impact on its structure and consequent role in diabetes. This study has probed the methylglyoxal mediated modifications of HSA, the alterations in its immunological characteristics and possible role in autoantibody induction. We observed an exposure of chromophoric groups, loss in the fluorescence intensity, generation of AGEs, formation of cross-linked products, decrease in α-helical content, increase in hydrophobic clusters, FTIR band shift, attachment of methylglyoxal to HSA and the formation of N(ε)-(carboxyethyl) lysine in the modified HSA, when compared to the native albumin. MG-HSA was found to be highly immunogenic with additional immunogenicity invoking a highly specific immune response than its native counterpart. The binding characteristics of circulating autoantibodies in type 2 diabetes mellitus (DM) patients showed the generation of anti-MG-HSA auto-antibodies in the these patients, that are preferentially recognized by the modified albumin. We propose that MG induced structural perturbations in HSA, result in the generation of neo-epitopes leading to an aggressive auto-immune response and may contribute to the immunopathogenesis of diabetes type 2 associated complications.

  16. Potentiation of alpha7-containing nicotinic acetylcholine receptors by select albumins.

    PubMed

    Conroy, William G; Liu, Qing-Song; Nai, Qiang; Margiotta, Joseph F; Berg, Darwin K

    2003-02-01

    Nicotinic receptors containing alpha7 subunits are ligand-gated ion channels widely distributed in the nervous system; they influence a diverse array of events because of their high relative calcium permeability. We show here that nicotine-induced whole-cell responses generated by such receptors can be dramatically potentiated in a rapidly reversible manner by some but not all albumins. The potentiation involves increases both in potency and efficacy with no obvious differences in rise and fall times of the response. The potentiation is not reduced by removing absorbed components; it is abolished by proteolysis, suggesting that the albumin protein backbone is essential. The fact that some albumins are ineffective indicates that minor differences in amino acid sequence may be critical. Experiments with open channel blockers indicate that the potentiation involves increased responses from active receptors rather than recruitment of receptors from a previously silent pool. Single channel recordings reveal that the potentiation correlates with increased single channel opening probability, reflected in increased frequency of channel opening and increased mean channel open time. The potentiation can be exploited to overcome blockade by noncompetitive inhibitors such as beta-amyloid peptide. The results raise the possibility that endogenous compounds use the site to modulate receptor function in vivo, and suggest that the receptors may represent useful targets for therapeutic intervention in cases where they have been implicated in neuropathologies such as Alzheimer's disease.

  17. Calorimetric investigation of diclofenac drug binding to a panel of moderately glycated serum albumins.

    PubMed

    Indurthi, Venkata S K; Leclerc, Estelle; Vetter, Stefan W

    2014-08-01

    Glycation alters the drug binding properties of serum proteins and could affect free drug concentrations in diabetic patients with elevated glycation levels. We investigated the effect of bovine serum albumin glycation by eight physiologically relevant glycation reagents (glucose, ribose, carboxymethyllysine, acetoin, methylglyoxal, glyceraldehyde, diacetyl and glycolaldehyde) on diclofenac drug binding. We used this non-steroidal anti-inflammatory drug diclofenac as a paradigm for acidic drugs with high serum binding and because of its potential cardiovascular risks in diabetic patients. Isothermal titration calorimetry showed that glycation reduced the binding affinity Ka of serum albumin and diclofenac 2 to 6-fold by reducing structural rigidity of albumin. Glycation affected the number of drug binding sites in a glycation reagent dependent manner and lead to a 25% decrease for most reagent, expect for ribose, with decreased by 60% and for the CML-modification, increased the number of binding sites by 60%. Using isothermal titration calorimetry and differential scanning calorimetry we derived the complete thermodynamic characterization of diclofenac binding to all glycated BSA samples. Our results suggest that glycation in diabetic patients could significantly alter the pharmacokinetics of the widely used over-the-counter NSDAI drug diclofenac and with possibly negative implications for patients.

  18. Albumin binds self-assembling dyes as specific polymolecular ligands.

    PubMed

    Stopa, Barbara; Rybarska, Janina; Drozd, Anna; Konieczny, Leszek; Król, Marcin; Lisowski, Marek; Piekarska, Barbara; Roterman, Irena; Spólnik, Paweł; Zemanek, Grzegorz

    2006-12-15

    Self-assembling dyes with a structure related to Congo red (e.g. Evans blue) form polymolecular complexes with albumin. The dyes, which are lacking a self-assembling property (Trypan blue, ANS) bind as single molecules. The supramolecular character of dye ligands bound to albumin was demonstrated by indicating the complexation of dye molecules outnumbering the binding sites in albumin and by measuring the hydrodynamic radius of albumin which is growing upon complexation of self-assembling dye in contrast to dyes lacking this property. The self-assembled character of Congo red was also proved using it as a carrier introducing to albumin the intercalated nonbonding foreign compounds. Supramolecular, ordered character of the dye in the complex with albumin was also revealed by finding that self-assembling dyes become chiral upon complexation. Congo red complexation makes albumin less resistant to low pH as concluded from the facilitated N-F transition, observed in studies based on the measurement of hydrodynamic radius. This particular interference with protein stability and the specific changes in digestion resulted from binding of Congo red suggest that the self-assembled dye penetrates the central crevice of albumin.

  19. Albumin Is Recycled from the Primary Urine by Tubular Transcytosis

    PubMed Central

    Tenten, Verena; Menzel, Sylvia; Kunter, Uta; Sicking, Eva-Maria; van Roeyen, Claudia R. C.; Sanden, Silja K.; Kaldenbach, Michaela; Boor, Peter; Fuss, Astrid; Uhlig, Sandra; Lanzmich, Regina; Willemsen, Brigith; Dijkman, Henry; Grepl, Martin; Wild, Klemens; Kriz, Wilhelm; Smeets, Bart; Floege, Jürgen

    2013-01-01

    Under physiologic conditions, significant amounts of plasma protein pass the renal filter and are reabsorbed by proximal tubular cells, but it is not clear whether the endocytosed protein, particularly albumin, is degraded in lysosomes or returned to the circulatory system intact. To resolve this question, a transgenic mouse with podocyte-specific expression of doxycycline-inducible tagged murine albumin was developed. To assess potential glomerular backfiltration, two types of albumin with different charges were expressed. On administration of doxycycline, podocytes expressed either of the two types of transgenic albumin, which were secreted into the primary filtrate and reabsorbed by proximal tubular cells, resulting in serum accumulation. Renal transplantation experiments confirmed that extrarenal transcription of transgenic albumin was unlikely to account for these results. Genetic deletion of the neonatal Fc receptor (FcRn), which rescues albumin and IgG from lysosomal degradation, abolished transcytosis of both types of transgenic albumin and IgG in proximal tubular cells. In summary, we provide evidence of a transcytosis within the kidney tubular system that protects albumin and IgG from lysosomal degradation, allowing these proteins to be recycled intact. PMID:23970123

  20. Effects of glycation on meloxicam binding to human serum albumin

    NASA Astrophysics Data System (ADS)

    Trynda-Lemiesz, Lilianna; Wiglusz, Katarzyna

    2011-05-01

    The current study reports a binding of meloxicam a pharmacologically important new generation, non-steroidal anti-inflammatory drug to glycated form of the human serum albumin (HSA). The interaction of the meloxicam with nonglycated and glycated albumin has been studied at pH 7.4 in 0.05 M sodium phosphate buffer with 0.1 M NaCl, using fluorescence quenching technique and circular dichroism spectroscopy. Results of the present study have shown that the meloxicam could bind both forms of albumin glycated and nonglycated at a site, which was close to the tryptophan residues. Similarly, how for native albumin glycated form has had one high affinity site for the drug with association constants of the order of 10 5 M -1. The glycation process of the HSA significantly has affected the impact of the meloxicam on the binding of other ligands such as warfarin and bilirubin. The affinity of the glycated albumin for bilirubin as for native albumin has been reduced by meloxicam but observed effect was weaker by half (about 20%) compared with nonglycated albumin. In contrast to the native albumin meloxicam binding to glycated form of the protein only slightly affected the binding of warfarin. It seemed possible that the effects on warfarin binding might be entirely attributable to the Lys 199 modification which was in site I.

  1. Single Pass Albumin Dialysis-A Dose-Finding Study to Define Optimal Albumin Concentration and Dialysate Flow.

    PubMed

    Schmuck, Rosa Bianca; Nawrot, Gesa-Henrike; Fikatas, Panagiotis; Reutzel-Selke, Anja; Pratschke, Johann; Sauer, Igor Maximilian

    2017-02-01

    Several artificial liver support concepts have been evaluated both in vitro and clinically. Single pass albumin dialysis (SPAD) has shown to be one of the most simple approaches for removing albumin-bound toxins and water-soluble substances. Being faced with acute liver failure (ALF) in everyday practice encouraged our attempt to define the optimal conditions for SPAD more precisely in a standardized experimental setup. Albumin concentration was adjusted to either 1%, 2%, 3%, or 4%, while the flow rate of the dialysate was kept constant at a speed of 700 mL/h. The flow rate of the dialysate was altered between 350, 500, 700, and 1000 mL/h, whereas the albumin concentration was continuously kept at 3%. This study revealed that the detoxification of albumin-bound substances could be improved by increasing the concentration of albumin in the dialysate with an optimum at 3%. A further increase of the albumin concentration to 4% did not lead to a significant increase in detoxification. Furthermore, we observed a gradual increase of the detoxification efficiency for albumin-bound substances, from 350 mL/h to 700 mL/h (for bilirubin) or 1000 mL/h (for bile acids) of dialysate flow. Water-soluble toxins (ammonia, creatinine, urea, uric acid) were removed almost completely, regardless of albumin concentration or flow rate. In conclusion, this study confirmed that SPAD is effective in eliminating albumin-bound as well as water-soluble toxins using a simulation of ALF. Furthermore, this project was successful in evaluating the most effective combination of albumin concentration (3%) and dialysate flow (700 mL/h-1000 mL/h) in SPAD for the first time. © 2016 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

  2. Affinity of human serum albumin for bilirubin varies with albumin concentration and buffer composition: results of a novel ultrafiltration method.

    PubMed

    Weisiger, R A; Ostrow, J D; Koehler, R K; Webster, C C; Mukerjee, P; Pascolo, L; Tiribelli, C

    2001-08-10

    Albumin binding is a crucial determinant of bilirubin clearance in health and bilirubin toxicity in certain disease states. However, prior attempts to measure the affinity of albumin for bilirubin have yielded highly variable results, reflecting both differing conditions and the confounding influence of impurities. We therefore have devised a method based on serial ultrafiltration that successively removes impurities in [(14)C]bilirubin until a stable binding affinity is achieved, and then we used it to assess the effect of albumin concentration and buffer composition on binding. The apparent binding affinity of human serum albumin for [(14)C]bilirubin was strongly dependent on assay conditions, falling from (5.09 +/- 0.24) x 10(7) liters/mol at lower albumin concentrations (15 microm) to (0.54 +/- 0.05) x 10(7) liters/mol at higher albumin concentrations (300 microm). To determine whether radioactive impurities were responsible for this change, we estimated impurities in the stock bilirubin using a novel modeling approach and found them to be 0.11-0.13%. Formation of new impurities during the study and their affinity for albumin were also estimated. After correction for impurities, the binding affinity remained heavily dependent on the albumin concentration (range (5.37 +/- 0.26) x 10(7) liters/mol to (0.65 +/- 0.03) x 10(7) liters/mol). Affinities decreased by about half in the presence of chloride (50 mm). Thus, the affinity of human albumin for bilirubin is not constant, but varies with both albumin concentration and buffer composition. Binding may be considerably less avid at physiological albumin concentrations than previously believed.

  3. Foam fractionation of binary mixtures of lysozyme and albumin.

    PubMed

    Lockwood, C E; Jay, M; Bummer, P M

    2000-06-01

    A nitrogen gas-based foam fractionation method was employed to separate model proteins, bovine serum albumin (BSA) and hen egg white lysozyme, from each other. Fractionation was characterized by the separation ratio and by recovery of proteins in the retentate as a function of the nominal pore size of the gas dispersion frit and solution conditions (pH and ionic strength). For binary mixtures of the proteins at pH 7.4, and ionic strength (mu) of 0.18 M, the recovery of lysozyme and the separation ratio were both dependent on the frit size employed to generate the foam. At low ionic strength (mu = 0.01 M), separation was only somewhat greater with the small pore size frits, although at values significantly lower than those found for high ionic strength. The diminished separations appear to be due to the only slight changes in recoveries observed for BSA and lysozyme.%Separation ratios of lysozyme from BSA in solutions either of high or low ionic strength were maximal at pH values equal to or less than the isoelectric point (pI) of BSA. Separation ratios were lower when foaming was carried out under low compared with high ionic strength. The recovery of lysozyme was enhanced by foaming from solutions of low pH and high ionic strength. Recoveries of BSA were greatest when the molecule was negatively charged. Electrical interactions between the positively charged lysozyme and negatively charged BSA may explain the diminished separation ratios and enhanced recoveries. Enzyme activity studies of lysozyme remaining in the retentate showed no change from prefoam activity.

  4. Low molecular weight silicones particularly facilitate human serum albumin denaturation.

    PubMed

    Nayef, Lamees M; Khan, Madiha F; Brook, Michael A

    2015-04-01

    There is a market trend towards the administration of therapeutic proteins using sterilized, pre-filled glass syringes lubricated with silicone oil. It has been widely reported that initially clear solutions of proteins can become turbid during transport and storage, with unclear outcomes with respect to bioefficacy. While the basic processes of interactions of proteins with hydrophobic entities, leading to denaturation and aggregation, are increasingly well understood, the apparently random occurrence of such processes in syringes is not. To better understand the parameters that may be responsible for this change, we report the systematic examination of a series of factors that can affect the behavior of the protein human serum albumin (HSA) when in contact with silicone oil in water. Fluorescence spectroscopy showed that greater mixing times and greater concentrations of silicones (polydimethylsiloxane (PDMS)), especially lower molecular weight hydrophobic silicones like octamethyltetracyclosiloxane (D4), were associated with increased protein denaturation. The turbidity of HSA solutions, due to the formation both of silicone oil-in-water (O/W) emulsions and protein aggregates, was also facilitated by the presence of D4. A series of mixtures of silicone oils, all of which exhibited a viscosity of 1000 cSt but which were comprised of different silicone constituents, clearly showed a correlation between the presence of lower molecular silicones and enhanced solution turbidity. While the addition of a non-ionic silicone-polyether surfactant led to greater turbidity by increasing the number of stabilized oil droplets, it was not accompanied by protein denaturation. These results are consistent with HSA denaturation and subsequent aggregation as a consequence of contact particularly with low molecular weight, hydrophobic silicones that are more mobile, leading to more efficient protein/silicone contact.

  5. Interaction of lipid vesicle with silver nanoparticle-serum albumin protein corona

    NASA Astrophysics Data System (ADS)

    Chen, Ran; Choudhary, Poonam; Schurr, Ryan N.; Bhattacharya, Priyanka; Brown, Jared M.; Chun Ke, Pu

    2012-01-01

    The physical interaction between a lipid vesicle and a silver nanoparticle (AgNP)-human serum albumin (HSA) protein "corona" has been examined. Specifically, the binding of AgNPs and HSA was analyzed by spectrophotometry, and the induced conformational changes of the HSA were inferred from circular dichroism spectroscopy. The fluidity of the vesicle, a model system for mimicking cell membrane, was found to increase with the increased exposure to AgNP-HSA corona, though less pronounced compared to that induced by AgNPs alone. This study offers additional information for understanding the role of physical forces in nanoparticle-cell interaction and has implications for nanomedicine and nanotoxicology.

  6. Ghrelin binding to serum albumin and its biological impact.

    PubMed

    Lufrano, Daniela; Trejo, Sebastián A; Llovera, Ramiro E; Salgueiro, Mariano; Fernandez, Gimena; Martínez Damonte, Valentina; González Flecha, F Luis; Raingo, Jesica; Ermácora, Mario R; Perelló, Mario

    2016-11-15

    Ghrelin is an octanoylated peptide hormone that plays a key role in the regulation of the body weight and glucose homeostasis. In plasma, ghrelin circulates bound to larger proteins whose identities are partially established. Here, we used size exclusion chromatography, mass spectrometry and isothermal titration microcalorimetry to show that ghrelin interacts with serum albumin. Furthermore, we found that such interaction displays an estimated dissociation constant (KD) in the micromolar range and involves albumin fatty-acid binding sites as well as the octanoyl moiety of ghrelin. Notably, albumin-ghrelin interaction reduces the spontaneous deacylation of the hormone. Both in vitro experiments-assessing ghrelin ability to inhibit calcium channels-and in vivo studies-evaluating ghrelin orexigenic effects-indicate that the binding to albumin affects the bioactivity of the hormone. In conclusion, our results suggest that ghrelin binds to serum albumin and that this interaction impacts on the biological activity of the hormone.

  7. [Indications of albumin for vascular loading during pregnancy].

    PubMed

    Palot, M; Visseaux, H; Pire, J C

    1996-01-01

    Albumin infusion is used during pregnancy for volume loading in preeclampsia and/or intra-uterine growth retardation, before regional anaesthesia for Caesarean section, compensation of blood loss during haemorrhages of parturition, as well as prevention and treatment of ovarian hyperstimulation syndrome after in vitro fertilization. In preeclampsia, albumin is used for volume loading before initiating antihypertensive therapy. However it neither decreases blood pressure, nor increases uterine blood flow. Before regional anaesthesia for Caesarean section, an infusion of albumin 5% at a rate of 15 mL.kg-1 prevents hypotension in mothers (P < 0.05 versus Ringer lactate) and provides better Apgar scores in neonates (P < 0.05). Albumin is used to treat hypovolaemia in severe ovarian hyperstimulation syndrome. Recent studies have shown that in patients at high risk of ovarian hyperstimulation syndrome, 500 mL albumin 5% administered after ovocytes retrieval diminished the incidence of this syndrome (P < 0.05 versus normal saline).

  8. Interaction of sulpiride and serum albumin: Modeling from spectrofluorimetric data

    NASA Astrophysics Data System (ADS)

    Fragoso, Viviane Muniz da Silva; Silva, Dilson

    2015-12-01

    We have applied the fluorescence quenching modeling to study the process of interaction of sulpiride with human serum albumin (HSA) and bovine (BSA). Albumin is more abundant protein in blood and it emits fluorescence when excited by 260-295 nm. Sulpiride is an atypical antipsychotic used in the treatment of many psychiatric disorders. As sulpiride is fluorescent, we developed a mathematical model to analyzing the interaction of two fluorescent substances. This model was able to separate the albumin fluorescence from the quencher fluorescence. Results have shown that sulpiride quenches the fluorescence of both albumins by a static process, due to the complex formation drugalbumin. The association constants calculated for sulpiride-HSA was 2.20 (± 0.08) × 104 M-1 at 37° C, and 5.46 (± 0.20) × 104 M-1, 25 ° C, and the primary binding site to sulpiride in the albumin is located closer to the subdomain IB.

  9. Interaction of coffee compounds with serum albumins. Part II: Diterpenes.

    PubMed

    Guercia, Elena; Forzato, Cristina; Navarini, Luciano; Berti, Federico

    2016-05-15

    Cafestol and 16-O-methylcafestol are diterpenes present in coffee, but whilst cafestol is found in both Coffea canephora and Coffea arabica, 16-O-methylcafestol (16-OMC) was reported to be specific of only C. canephora. The interactions of such compounds, with serum albumins, have been studied. Three albumins have been considered, namely human serum albumin (HSA), fatty acid free HSA (ffHSA) and bovine serum albumin (BSA). The proteins interact with the diterpenes at the interface between Sudlow site I and the fatty acid binding site 6 in a very peculiar way, leading to a significant change in the secondary structure. The diterpenes do not displace reference binding drugs of site 2, but rather they enhance the affinity of the site for the drugs. They, therefore, may alter the pharmacokinetic profile of albumin - bound drugs. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Serum albumin induces osmotic swelling of rat retinal glial cells.

    PubMed

    Löffler, Silvana; Wurm, Antje; Kutzera, Franziska; Pannicke, Thomas; Krügel, Katja; Linnertz, Regina; Wiedemann, Peter; Reichenbach, Andreas; Bringmann, Andreas

    2010-03-04

    Edema in the ischemic neural tissue develops by increased vascular permeability associated with extravasation of albumin, and by glial swelling. Here, we show that bovine serum albumin acutely administered to slices of the rat retina causes swelling of glial somata under hypoosmotic conditions. The effect of albumin was dose-dependent, with half-maximal and maximal effects at 10 nM and 1 microM, respectively, and was mediated by activation of transforming growth factor-beta receptor type II, oxidative stress, and the production of arachidonic acid and prostaglandins. Albumin-induced glial swelling was prevented by glutamate and purinergic receptor agonists. The data suggest that serum albumin may induce glial swelling in the presence of osmotic gradients.

  11. Platelet retention by albuminated glass and polystyrene beads.

    PubMed

    Coleman, D L; Atwood, A I; Andrade, J D

    1976-11-01

    Ex vivo platelet retention by albuminated glass and polystyrene beads has been evaluated as a function of flow rate, bead surface area, blood exposure time and albumin treatment. The stability of the albumin coatings as well as scanning electron microscopy of the various surfaces before and after blood exposure has also been included. Results indicate that platelet retention is sensitive to changes in the above parameters and that albumin pretreatment of different substrates can decrease platelet retention. This decrease is substrate dependent in that platelet retention is different for the albuminated glass and polystyrene substrates. Chemical analysis of the substrate materials by X-ray photoelectron spectroscopy (XPS) as well as bulk chemical analysis is also reported.

  12. Laboratory reporting of urine protein and albumin.

    PubMed

    Jones, Graham Rd

    2011-05-01

    Communication between pathology laboratories and clients involves more than just a result. There may be advice on recommended specimen type as well as the units and reference intervals used to report results. Between-laboratory variability in these factors has the potential to cause unnecessary confusion and even to lead to variation in interpretation for samples sent to different laboratories. A survey of Australian and New Zealand laboratories covering sample recommendations, specimens received, units and reference intervals for urine albumin and urine protein was conducted through the Royal College of Pathologists of Australasia Quality Assurance Program (RCPA QAP). The results confirm earlier findings of wide between-laboratory variability in all these factors. It is proposed that only recommendations developed by relevant professional societies and adopted by all laboratories can lead to reduction in this variability.

  13. Cubilin Maintains Blood Levels of HDL and Albumin

    PubMed Central

    Aseem, Obaidullah; Smith, Brian T.; Cooley, Marion A.; Wilkerson, Brent A.; Argraves, Kelley M.; Remaley, Alan T.

    2014-01-01

    Cubilin is an endocytic receptor highly expressed in renal proximal tubules, where it mediates uptake of albumin and filtered forms of apoA-I/HDL. Cubilin deficiency leads to urinary loss of albumin and apoA-I; however, the consequences of cubilin loss on the homeostasis of blood albumin and apoA-I/HDL have not been studied. Using mice heterozygous for cubilin gene deletion (cubilin HT mice), we show that cubilin haploinsufficiency leads to reduced renal proximal tubular uptake of albumin and apoA-I and significantly increased urinary loss of albumin and apoA-I. Moreover, cubilin HT mice displayed significantly decreased blood levels of albumin, apoA-I, and HDL. The levels of albumin and apoA-I protein or mRNA expressed in the liver, kidney, or intestine of cubilin HT mice did not change significantly. The clearance rate of small HDL3 particles (density>1.13 g/ml) from the blood increased significantly in cubilin HT mice. In contrast, the rate of clearance of larger HDL2 particles from the blood did not change significantly, indicating a decreased half-life for HDL particles capable of filtering through the glomerulus. On the basis of these findings, we conclude that cubilin deficiency reduces renal salvage and delivery back to the blood of albumin and apoA-I, which decreases blood levels of albumin and apoA-I/HDL. These findings raise the possibility that therapeutic increase of renal cubilin expression might reduce proteinuria and increase blood levels of albumin and HDL. PMID:24357674

  14. Thrombin-induced increase in albumin permeability across the endothelium

    SciTech Connect

    Garcia, J.G.; Siflinger-Birnboim, A.; Bizios, R.; Del Vecchio, P.J.; Fenton, J.W. 2d.; Malik, A.B.

    1986-07-01

    We studied the effect of thrombin on albumin permeability across the endothelial monolayer in vitro. Bovine pulmonary artery endothelial cells were grown on micropore membranes. Morphologic analysis confirmed the presence of a confluent monolayer with interendothelial junctions. Albumin permeability was measured by the clearance of 125I-albumin across the endothelial monolayer. The control 125I-albumin clearance was 0.273 +/- 0.02 microliter/min. The native enzyme, alpha-thrombin (10(-6) to 10(-10) M), added to the luminal side of the endothelium produced concentration-dependent increases in albumin clearance (maximum clearance of 0.586 +/- 0.08 microliter/min at 10(-6) M). Gamma (gamma) thrombin (10(-6) M and 10(-8) M), which lacks the fibrinogen recognition site, also produced a concentration-dependent increase in albumin clearance similar to that observed with alpha-thrombin. Moreover, the two proteolytically inactive forms of the native enzyme, i-Pr2 P-alpha-thrombin and D-Phe-Pro-Arg-CH2-alpha-thrombin, increased the 125I-albumin clearance (0.610 +/- 0.09 microliter/min and 0.609 +/- 0.02 microliter/min for i-Pr2 P-alpha-thrombin and D-Phe-Pro-Arg-CH2-alpha-thrombin at 10(-6) M, respectively). Since the modified forms of thrombin lack the fibrinogen recognition and active serine protease sites, the results indicate that neither site is required for increased albumin permeability. The increase in albumin clearance with alpha-thrombin was not secondary to endothelial cell lysis because lactate dehydrogenase concentration in the medium following thrombin was not significantly different from baseline values. There was also no morphological evidence of cell lysis. Moreover, the increase in 125I-albumin clearance induced by alpha-thrombin was reversible by washing thrombin from the endothelium.

  15. Cubilin maintains blood levels of HDL and albumin.

    PubMed

    Aseem, Obaidullah; Smith, Brian T; Cooley, Marion A; Wilkerson, Brent A; Argraves, Kelley M; Remaley, Alan T; Argraves, W Scott

    2014-05-01

    Cubilin is an endocytic receptor highly expressed in renal proximal tubules, where it mediates uptake of albumin and filtered forms of apoA-I/HDL. Cubilin deficiency leads to urinary loss of albumin and apoA-I; however, the consequences of cubilin loss on the homeostasis of blood albumin and apoA-I/HDL have not been studied. Using mice heterozygous for cubilin gene deletion (cubilin HT mice), we show that cubilin haploinsufficiency leads to reduced renal proximal tubular uptake of albumin and apoA-I and significantly increased urinary loss of albumin and apoA-I. Moreover, cubilin HT mice displayed significantly decreased blood levels of albumin, apoA-I, and HDL. The levels of albumin and apoA-I protein or mRNA expressed in the liver, kidney, or intestine of cubilin HT mice did not change significantly. The clearance rate of small HDL3 particles (density>1.13 g/ml) from the blood increased significantly in cubilin HT mice. In contrast, the rate of clearance of larger HDL2 particles from the blood did not change significantly, indicating a decreased half-life for HDL particles capable of filtering through the glomerulus. On the basis of these findings, we conclude that cubilin deficiency reduces renal salvage and delivery back to the blood of albumin and apoA-I, which decreases blood levels of albumin and apoA-I/HDL. These findings raise the possibility that therapeutic increase of renal cubilin expression might reduce proteinuria and increase blood levels of albumin and HDL.

  16. Impact of heat treatment on miscibility of proteins and disaccharides in frozen solutions.

    PubMed

    Izutsu, Ken-ichi; Yomota, Chikako; Okuda, Haruhiro; Kawanishi, Toru; Randolph, Theodore W; Carpenter, John F

    2013-10-01

    The purpose of this study was to elucidate the effect of heat treatment (annealing) on the miscibility of concentrated protein and disaccharide mixtures in the freezing segment of lyophilization. Frozen solutions containing a protein (e.g., recombinant human albumin, chicken egg lysozyme, bovine plasma immunoglobulin G, or a humanized IgG1k monoclonal antibody) and a non-reducing disaccharide (e.g., sucrose or trehalose) showed single thermal transitions of the solute mixtures (glass transition temperature of maximally freeze-concentrated solutes: T(g)(')) in their first heating scans. Heat treatment (e.g., -5 °C, 30 min) of some disaccharide-rich mixture frozen solutions at temperatures far above their T(g)(') induced two-step T(g)(') transitions in the subsequent scans, suggesting the separation of the solutes into concentrated protein-disaccharide mixture phase and disaccharide phase. Other frozen solutions showed a single transition of the concentrated solute mixture both before and after heat treatment. The apparent effects of the heat treatment temperature and time on the changes in thermal properties suggest molecular reordering of the concentrated solutes from a kinetically fixed mixture state to a more thermodynamically favorable state as a result of increased mobility. The implications of these phenomena on the quality of protein formulations are discussed. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. An artificially evolved albumin binding module facilitates chemical shift epitope mapping of GA domain interactions with phylogenetically diverse albumins.

    PubMed

    He, Yanan; Chen, Yihong; Rozak, David A; Bryan, Philip N; Orban, John

    2007-07-01

    Protein G-related albumin-binding (GA) modules occur on the surface of numerous Gram-positive bacterial pathogens and their presence may promote bacterial growth and virulence in mammalian hosts. We recently used phage display selection to evolve a GA domain, PSD-1 (phage selected domain-1), which tightly bound phylogenetically diverse albumins. With respect to PSD-1's broad albumin binding specificity, it remained unclear how the evolved binding epitope compared to those of naturally occurring GA domains and whether PSD-1's binding mode was the same for different albumins. We investigate these questions here using chemical shift perturbation measurements of PSD-1 with rabbit serum albumin (RSA) and human serum albumin (HSA) and put the results in the context of previous work on structure and dynamics of GA domains. Combined, these data provide insights into the requirements for broad binding specificity in GA-albumin interactions. Moreover, we note that using the phage-optimized PSD-1 protein significantly diminishes the effects of exchange broadening at the binding interface between GA modules and albumin, presumably through stabilization of a ligand-bound conformation. The employment of artificially evolved domains may be generally useful in NMR structural studies of other protein-protein complexes.

  18. Predictive Value of Serum Albumin Level for the Prognosis of Severe Sepsis Without Exogenous Human Albumin Administration.

    PubMed

    Yin, Mei; Si, Lei; Qin, Weidong; Li, Chen; Zhang, Jianning; Yang, Hongna; Han, Hui; Zhang, Fan; Ding, Shifang; Zhou, Min; Wu, Dawei; Chen, Xiaomei; Wang, Hao

    2016-01-01

    The prognostic significance of serum albumin levels in patients with sepsis has previously been reported; however, these studies have not excluded the potential confounding effect of exogenous albumin administration. In this study, we investigate the predictive value of serum albumin for the prognosis of severe sepsis without the interference of exogenous albumin administration. A prospective cohort study was conducted from April to November 2014 in the internal and surgical intensive care units of a tertiary care hospital. During the study period, due to a supply shortage, patients were not treated with human albumin. Serum albumin levels were measured, and laboratory and clinical data were collected at the onset of severe sepsis. Prognostic factors were analyzed using receiver operating characteristic curve and multivariate Cox proportional hazard regression analysis. Survival was assessed by Kaplan-Meier method. One hundred sixteen patients were included in the study. The overall 28-day mortality was 26.7%. The most common infection sources were lower respiratory tract, abdomen/pelvis, and bloodstream. Compared to patients who survived, those who died had lower serum albumin levels and higher Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA) scores. Receiver operating characteristic curves demonstrate that albumin level is a strong predictor of 28-day mortality, and the optimal cutoff value maximizing sensitivity and specificity is 29.2 g/L. Through multivariate Cox regression analysis, low serum albumin levels (<29.2 g/L) and APACHE II scores are identified as independent risk factors for mortality. Patients with lower serum albumin levels more often had abdominal/pelvic sources of infection, acute kidney or liver injury, septic shock, and higher APACHE II and SOFA scores. The 28-day survival rate was lower for patients with serum albumin below 29.2 g/L than for patients with serum albumin at or above

  19. Rheological aspects of mucin-containing solutions and saliva substitutes.

    PubMed

    Mellema, J; Holterman, H J; Waterman, H A; Blom, C; Gravenmade, E J

    1992-01-01

    In this study rheological properties of aqueous solutions of mucin, albumin and mucin-albumin have been investigated in search for saliva substitutes. They were compared with commercially available saliva substitutes on the one hand and natural human saliva on the other hand. For the latter a few measurements on saliva are reported here in addition to previously reported measurements done in our laboratory. Proteins absorb at the interface and saliva proteins do so strongly and rapidly. Therefore rheological measurements were carried out on the interface and on the bulk underneath the layer. In both cases the flow curve and the complex viscosity was determined. The results show that specific mucin-albumin solutions were rheologically similar to human whole saliva with respect to both bulk liquid and surface properties. The rheological properties of commercial saliva substitutes were essentially different from those of human saliva. It is concluded that mucin-albumin solutions have good perspectives as saliva substitutes.

  20. Study of the cross-reaction between rabbit anti-bovine serum albumin antibodies and equine serum albumin

    PubMed Central

    Rangel, H.

    1965-01-01

    Cross-reactions between bovine serum albumin and equine serum albumin were studied using heterologous soluble complexes and specifically purified cross-reacting antibody. Experiments with soluble complexes showed that homologous antigen can displace heterologous antigen specifically bound to antibody but heterologous antigen cannot displace homologous antigen. On gel precipitation tests a specific precipitation resulted when heterologous soluble complex reacted with homologous antigen. By using equine serum albumin conjugated to polyaminopolystyrene the cross-reacting antibodies from anti-bovine serum albumin imune sera could be isolated. These are divalent 7S, γ-globulin antibodies. A figure of cross-reaction was obtained when these purified antibodies were tested by double diffusion in agar with bovine and equine serum albumins. The results obtained both with soluble complexes and with purified antibody support the view that cross-reacting antibody is more avid for the homologous than for the heterologous antigen. ImagesFIG. 3FIG. 4FIG. 5 PMID:14245318

  1. Interactions of human serum albumin with doxorubicin in different media

    NASA Astrophysics Data System (ADS)

    Gun'ko, Vladimir M.; Turov, Vladimir V.; Krupska, Tetyana V.; Tsapko, Magdalina D.

    2017-02-01

    Interactions of human serum albumin (10 wt% H2O and 0.3 wt% sodium caprylate) with doxorubicin hydrochloride (1 wt%) were studied alone or with addition of HCl (3.6 wt% HCl) using 1H NMR spectroscopy. A model of hydrated HSA/12DOX was calculated using PM7 method with COSMO showing large variations in the binding constant depending on structural features of DOX/HSA complexes. DOX molecules/ions displace bound water from narrow intramolecular voids in HSA that leads to diminution of freezing-melting point depression of strongly bound water (SBW). Structure of weakly bound water (WBW) depends much weaker on the presence of DOX than SBW because a major fraction of DOX is bound to adsorption sites of HSA. Addition of HCl results in strong changes in structure of macromolecules and organization of water in hydration shells of HSA (i.e., mainly SBW) and in the solution (i.e., WBW + non-bound bulk water).

  2. [Effect of tobacco combustion on the immunochemical properties of albumin].

    PubMed

    Martínez, R D; Chávez, R

    1997-01-01

    During tobacco burning smoker to run up substances to contain smoke as far as pulmonary tissue that is damage. In cigarette 600 degrees C are in ignition extreme, but in the other side, in contact with edge of the mouth smoker, the temperature is lower. Smoke could be delivery tobacco products until respiratory tract when temperature gradients occur in cigarette burn. For demonstration of the immunoreactive substances in tobacco smoke condense (TSC) we used a model with two cigarette arrangements: several concentrations of bovine seric albumin (BSA) applied to experimental group of cigarettes and phosphate-saline solution (PBS), 0.15 M pH 7.5 without protein to control cigarettes. Both series, experimental and control, remained at 20 degrees C during 48 h, soon afterward TSC was obtained. Higher protein concentration was observe in the experimental TSC of cigarettes expose to more elevated quantities of BSA, this was identify with polyclonal antibodies toward BSA employing counter-immunoelectrophoresis, immunoelectrophoresis, radial immunodiffusion and hemagglutination inhibition test. In summary: TSC of treat cigarettes had a little quantity of protein (BSA), but immunochemical properties of BSA in TSC were preserve because polyclonal antibodies against BSA bind to this protein. In habitual smoker some compounds present in cigarette smoke could be induce an immune response due to immunogen in tobacco substances.

  3. Serum albumin in 2D: a Langmuir monolayer approach.

    PubMed

    Crawford, Nicholas F; Leblanc, Roger M

    2014-05-01

    Understanding of protein interaction at the molecular level raises certain difficulties which is the reason a model membrane system such as the Langmuir monolayer technique was developed. Ubiquitous proteins such as serum albumin comprise 50% of human blood plasma protein content and are involved in many biological functions. The important nature of this class of protein demands that it be studied in detail while modifying the experimental conditions in two dimensions to observe it in all types of environments. While different from bulk colloidal solution work, the two dimensional approach allows for the observation of the interaction between molecules and subphase at the air-water interface. Compiled in this review are studies which highlight the characterization of this protein using various surroundings and also observing the types of interactions it would have when at the biomembrane interface. Free-energy changes between molecules, packing status of the bulk analyte at the interface as well as phase transitions as the monolayer forms a more organized or aggregated state are just some of the characteristics which are observed through the Langmuir technique. This unique methodology demonstrates the chemical behavior and physical behavior of this protein at the phase boundary throughout the compression of the monolayer. © 2013 Elsevier B.V. All rights reserved.

  4. Virus-Enabled Biosensor for Human Serum Albumin.

    PubMed

    Ogata, Alana F; Edgar, Joshua M; Majumdar, Sudipta; Briggs, Jeffrey S; Patterson, Shae V; Tan, Ming X; Kudlacek, Stephan T; Schneider, Christine A; Weiss, Gregory A; Penner, Reginald M

    2017-01-17

    The label-free detection of human serum albumin (HSA) in aqueous buffer is demonstrated using a simple, monolithic, two-electrode electrochemical biosensor. In this device, both millimeter-scale electrodes are coated with a thin layer of a composite containing M13 virus particles and the electronically conductive polymer poly(3,4-ethylenedioxy thiophene) or PEDOT. These virus particles, engineered to selectively bind HSA, serve as receptors in this biosensor. The resistance component of the electrical impedance, Zre, measured between these two electrodes provides electrical transduction of HSA binding to the virus-PEDOT film. The analysis of sample volumes as small as 50 μL is made possible using a microfluidic cell. Upon exposure to HSA, virus-PEDOT films show a prompt increase in Zre within 5 s and a stable Zre signal within 15 min. HSA concentrations in the range from 100 nM to 5 μM are detectable. Sensor-to-sensor reproducibility of the HSA measurement is characterized by a coefficient-of-variance (COV) ranging from 2% to 8% across this entire concentration range. In addition, virus-PEDOT sensors successfully detected HSA in synthetic urine solutions.

  5. Size exclusion chromatographic analysis of polyphenol-serum albumin complexes.

    PubMed

    Hatano, Tsutomu; Hori, Mami; Hemingway, Richard W; Yoshida, Takashi

    2003-08-01

    Formation of water-soluble polyphenol-protein complexes was investigated by size-exclusion chromatography (SEC). The combination of (-)-epigallocatechin gallate (EGCG) and bovine serum albumin (BSA), which did not form a precipitate after the solutions were mixed, showed an SEC peak due to complex formation 2-24 h after mixing. Peak size of the complex varied with time, suggesting slow change of the conformation of the protein accompanied by complexation. Formation of the complex was substantiated by ultrafiltration of the mixture; the complex did not pass through a membrane with a 100,000 nominal molecular weight limit (NMWL). The SEC profile varied with the combination of compounds. The peaks due to the complexes showed that the apparent value of the number average molecular weight (M(n)) of the EGCG-BSA complex was 2.8x10(5), while that of a pentagalloylglucose (PGG)-BSA complex was 9.5x10(5) under the conditions used. Dimeric hydrolyzable tannins, oenothein B and cornusiin A, also caused changes in the SEC profile of BSA, although the combinations did not show peaks attributable to formation of such large complexes observed for EGCG and PGG. Procyanidin B3 and (+)-catechin did not cause changes in the SEC profile of BSA. With cytochrome c, EGCG did not show any chromatographic changes.

  6. Elevation of CSF albumin in old sheep: relations to CSF turnover and albumin extraction at blood-CSF barrier.

    PubMed

    Chen, Ruo-Li; Chen, Carl Pai-Chu; Preston, Jane Elizabeth

    2010-06-01

    Albumin is the most abundant protein in both CSF and plasma, and albumin quotient is often used to assess the functions of brain barriers especially that of the blood-CSF barrier [i.e. the choroid plexus (CP) which also secretes CSF]. In this study, we took albumin as a model molecule to investigate ageing-related alterations in the CSF-CP system in sheep. We found significant ageing-related increases in the weight of lateral CP [122.4 +/- 14.0 mg in the young, 198.6 +/- 35.4 mg in the middle aged, 286.1 +/- 25.1 mg in the old (p < 0.05)], in the CSF albumin as well as the albumin quotient. Albumin protein spots in old CSF displayed wider on 2D western immunoblotting images, and had higher densities on images of 2D large gels stained with Pro-Q Emerald 488 compared to the young samples, suggesting ageing-related post-translational modification in the albumin. CSF secretion was reduced with age: 0.148 +/- 0.013 mL/min/g in the young, 0.092 +/- 0.02 mL/min/g in the middle aged, 0.070 +/- 0.013 mL/min/g in the old (p < 0.05). The (125)I-BSA extraction was not different among the sheep groups, nor was altered by temperature reduction, monensin, nocodazole, anti-transforming growth factor beta receptor II antibody, as well as unlabelled albumins. In conclusion, elevation of albumin in old CSF is associated with reduced CSF secretion by the CP, which size increases with age. (125)I-BSA extract, reflecting the extracellular space rather than the active albumin uptake in the CP, is not different between ages. These early changes in health ageing may result in the accumulation and modifications of CSF proteins leading to neurotoxicity.

  7. Bilirubin-albumin binding, bilirubin/albumin ratios, and free bilirubin levels: where do we stand?

    PubMed

    Hulzebos, Christian V; Dijk, Peter H

    2014-11-01

    Treatment for unconjugated hyperbilirubinemia is predominantly based on one parameter, i.e., total serum bilirubin (TSB) levels. Yet, overt kernicterus has been reported in preterm infants at relatively low TSB levels, and it has been repeatedly shown that free unconjugated bilirubin (freeUCB) levels, or bilirubin/albumin (B/A) ratios for that matter, are more closely associated with bilirubin neurotoxicity. In this article, we review bilirubin-albumin binding, UCBfree levels, and B/A ratios in addition to TSB levels to individualize and optimize treatment especially in preterm infants. Methods to measure bilirubin-albumin binding or UCBfree are neither routinely performed in Western clinical laboratories nor incorporated in current management guidelines on unconjugated hyperbilirubinemia. For bilirubin-albumin binding, this seems justified because several of these methods have been challenged, and sufficiently powered prospective trials on the clinical benefits are lacking. Technological advances in the measurement of UCBfree may provide a convenient means for integrating UCBfree measurements into routine clinical management of jaundiced infants. A point-of-care method, as well as determination of UCBfree levels in various newborn populations, is desirable to learn more about variations in time and how various clinical pathophysiological conditions affect UCBfree levels. This will improve the estimation of approximate UCBfree levels associated with neurotoxicity. To delineate the role of UCBfree in the management of jaundiced (preterm) infants, trials are needed using UCBfree as treatment parameter. The additional use of the B/A ratio in jaundiced preterms has been evaluated in the Bilirubin Albumin Ratio Trial (BARTrial; Clinical Trials: ISRCTN74465643) but failed to demonstrate better neurodevelopmental outcome in preterm infants <32 weeks assigned to the study group. Awaiting a study in which infants are assigned to be managed solely on the basis of their B

  8. Metal Concentrations of Mississippi Valley-type Ore Fluids Predicted from Solid Solution Metal Concentrations in Ore-Stage Calcite and Implications for Ore Formation

    NASA Astrophysics Data System (ADS)

    Smith, S. E.; Appold, M. S.

    2016-12-01

    Mississippi-Valley-type (MVT) ore deposits represent significant enrichments of Zn, Pb, Ba, and F in the Earth's crust. Knowledge of the ore fluid concentrations of these elements is key to understanding their transport and precipitation to form deposits. LA-ICP-MS analyses of fluid inclusions have been the principle method used in recent research to determine the composition of MVT ore fluids. However, LA-ICP-MS results for Pb and Zn concentrations are ambiguous due to interferences from the host mineral matrix or possibly mineral accidentals within the fluid inclusions, motivating research for other methods to determine metal concentrations in MVT ore fluids. The present study was undertaken in an attempt to calculate ore fluid metal concentrations from their solid solution concentration in ore-stage calcite. Experimental distribution coefficients from Rimstidt et al. (1998) at 100° C were used in conjunction with solid solution metal concentrations of ore-stage calcite from the Illinois-Kentucky (IK) and Central-Tennessee (CT) MVT districts to predict ore fluid concentrations of Zn, Fe, Mg, and Mn. Predicted Mg and Mn ore fluid concentrations, which along with Zn and Fe form carbonate minerals (magnesite, rhodochrosite, smithsonite, and siderite) with the calcite structure, agreed well with available fluid inclusion data for these elements. Thus, the 1's of ppm Zn and 0.1's to 1's of ppm Fe ore fluid concentrations predicted in this study are also likely to be correct. Conversely, the predicted ore fluid concentrations of Sr and Ba, which along with Pb form carbonate minerals (strontianite, witherite, and cerrusite) with the aragonite structure, were in poor agreement with available fluid inclusion data for these elements. Thus, the predicted 1's of ppm ore fluid concentrations of Pb are unlikely to be accurate. The Zn concentrations calculated in this study for the IK and CT ore fluids have direct implications for the time needed to form the ores in these

  9. Uptake and Reactions of Formaldehyde, Acetaldehyde, Acetone, Propanal and Ethanol in Sulfuric Acid solutions at 200-240 K: Implications for upper tropospheric aerosol composition

    NASA Astrophysics Data System (ADS)

    Iraci, L. T.; Williams, M. B.; Axson, J.; Michelsen, R.

    2007-12-01

    The production of light absorbing, organic material in aerosol that is normally considered to be transparent in the UV and visible wavelength regions has significant implications for biogeochemical cycling and climate modelling. Production mechanisms likely involve carbonyl compounds such as formaldehyde, acetone, acetaldehyde and propanal that are present in significant quantities in the upper troposphere (UT). In this study, we have performed experiments focusing on a class of acid catalyzed carbonyl reactions, the formation of acetals. R2C=O + 2R'OH --> R2C(OR')2 + H2O Using a Knudsen cell apparatus, we have measured the rate of uptake of formaldehyde, acetaldehyde, acetone, propanal, and ethanol into sulfuric acid solutions ranging between 40-70 wt% of acid, containing 0-0.1 M of ethanol, acetone or formaldehyde at temperatures of 220-250 K. For all reactant pairs, the aldol condensation path, including self reaction, should be insignificant at the acidities studied. Evidence for reaction between organics was observed for all pairs, except those involving propanal which were likely limited by the very low solubility. We attribute enhanced uptake to the formation of acetals, such as 1,1-diethoxyethane and 2,2- diethoxypropane, among others. Enhanced uptake was observed to proceed on timescales > 1 hour and sometimes shows complex dependence on acidity that is likely related to speciation of the individual carbonyls in acidic solution. The acetal products do not absorb in the visible but are less volatile than parent molecules, allowing for accumulation in sulfuric acid particles, and enhanced uptake. Cross reactions of carbonyls with alcohols in sulfuric acid medium have not been previously measured, yet methanol and ethanol show high solubility and are present at significant concentrations in the UT. Thus even at slow reaction rates, the acetal reaction has ample starting material and proceeds under conditions common to the UT. We will present results for the

  10. Albumin infusion may deleteriously promote extracellular fluid overload without improving circulating hypovolemia in patients of advanced cirrhosis with diabetes mellitus and sepsis.

    PubMed

    Kumar, Ramesh; Kumar, Sachin; Lata, Suman

    2013-04-01

    In patients with liver cirrhosis, albumin is given to improve relative hypovolemia caused by marked splanchnic arteriolar vasodilatation. However, the volume effect of albumin is not predictable and depends also on capillary permeability, hydrostatic pressure and lymphatic ability to re-circulate albumin from interstitium to plasma. In patients with decompensated cirrhosis, the capillary permeability is increased, hydrostatic pressure is higher, and the lymphatics functions are deficient. Hence the albumin molecules are more likely to be extravasated rapidly into the interstitium and are subsequently less likely to be re-circulated back into the plasma. This would not only fail to correct circulating hypovolemia, the purpose for which it is given, but also would favor development of reverse colloid oncotic pressure and fluid movement out of the capillaries leading to development of edema. Thus, anything else which could further increase capillary permeability or hydrostatic pressure in cirrhotic patients might create more problems with albumin infusion. An increased capillary permeability is the hallmark of diabetes mellitus. Furthermore, diabetes mellitus may worsen immunodepression in cirrhotic patients thus increasing the incidence of severe infections which may further have a deleterious effect on hemodynamics and capillary permeability. A diabetic patient with advanced cirrhosis and sepsis usually has markedly increased capillary permeability, high hydrostatic pressure due to hyperdynamic circulation, and compromised lymphatic drainage capacity. Hence, using albumin infusion in them would not only fail to improve relative hypovolemia, but also would deleteriously promote extravascular accumulation of fluid, which might impair the functions of many vital organs. However, the efficacy and safety of albumin infusion in diabetic patients with advanced cirrhosis and sepsis is not known. Such data can have a great clinical implication and would necessitate search of

  11. Albumin micro/nanoparticles entrapping liposomes for itraconazole green formulation.

    PubMed

    de Jesús Valle, María José; Maderuelo Martín, Cristina; Zarzuelo Castañeda, Aránzazu; Sánchez Navarro, Amparo

    2017-08-30

    Itraconazole-loaded micro/nanoparticles containing albumin and liposomes were prepared by a technological process that avoids the use of organic solvents and crosslinker agents. The particles were characterized, lyophilized and formulated as tablets. Dynamic light scattering was used to determine the hydrodynamic diameter and zeta potential of the particles; optical and scanning-electron microscopy was used to evaluate their morphology. Spherical shaped particles of different sizes and zeta potential were obtained. An exponential relationship between the zeta potential and the albumin/cationic lipid molar ratio was established. Drug entrapment efficiency values were in the range of 51-68%, with no statistical differences among albumin feeding concentrations. Mannitol was used as lyophilization additive and the freeze-dried cake was directly compressed into tablets, suitable for vaginal administration. The results from the in vitro drug delivery assay show the influence of albumin on the itraconazole delivery profile; a rapid release was observed for particles with higher albumin amount compared to those with lower protein content. According to the results of this study, albumin particles entrapping liposomes prove to be a green pharmaceutical vehicle with a high potential for delivery of hydrophobic and highly albumin-bound drugs. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Albumin grafting on biomaterial surfaces using gamma-irradiation

    SciTech Connect

    Kamath, K.R.

    1993-01-01

    Surface modification has been used extensively in various fields to introduce desirable surface properties without affecting the bulk properties of the material. In the area of biomaterials, the approach of surface modification offers an effective alternative to the synthesis of new biomaterials. The specific objective of this study was to modify different biomaterial surfaces by albumin grafting to improve their blood compatibility. The modified surfaces were characterized for surface-induced platelet activation and thrombus formation. This behavior was correlated with the conditions used for grafting. In particular, albumin was functionalized to introduce pendant double bonds into the molecule. The functionalized albumin was covalently attached to various surfaces, such as dimethyldichlorosilane-coated glass, polypropylene, polycarbonate, poly(vinyl chloride), and polyethylene by gamma-irradiation. Platelet adhesion and activation on these surfaces was examined using video microscopy and scanning electron microscopy. The extent of grafting was found to be dependent on the albumin concentration used for adsorption and the gamma-irradiation time. Release of the grafted albumin during exposure to blood was minimal. The albumin-grafted fibers maintained their thromboresistant properties even after storage at elevated temperatures for prolonged time periods. Finally, the approach was used to graft albumin on the PLEXUS Adult Hollow Fiber Oxygenators (Shiley). The blood compatibility of the grafted oxygenators improved significantly when compared to controls.

  13. Nephroprotective Potential of Human Albumin Infusion: A Narrative Review

    PubMed Central

    Wiedermann, Christian J.; Joannidis, Michael

    2015-01-01

    Albumin infusion improves renal function in cirrhosis; however, mechanisms are incompletely understood. In clinical practice, human albumin is used in various intensive care unit indications to deal with a wide range of problems, from volume replacement in hypovolemic shock, or sepsis, to treatment of ascites in patients with liver cirrhosis. Against the background of the results of recent studies on the use of human albumin in septic patients, the importance of the natural colloid in these critically ill patients is being redefined. In addition to the hemodynamic effects of administration of human albumin impacting on sympathetic tone, attention is being paid to other effects in which its pharmacodynamics is associated with the physiological importance of endogenous albumin. The morbidity and mortality data discussed in this paper support the importance of both the hemodynamic and the pharmacological effects of the administration of human albumin in various indications. The contribution that human albumin could make towards the maintenance of renal function in the course and treatment of severe sepsis and cirrhosis of the liver is the subject of this narrative review. PMID:26136776

  14. Albumin, steroid hormones and the origin of vertebrates.

    PubMed

    Baker, M E

    2002-10-01

    Albumin, the major serum protein, binds a wide variety of lipophilic compounds including steroids, other lipophilic hormones and various phytochemicals and xenobiotics that bind to receptors for steroids and other lipophilic hormones. Despite albumin's low affinity (K(d) approximately 10(-4) M to 10(-6) M) for these lipophilic compounds, the high concentration of albumin in serum makes this protein a major carrier of steroids and lipophilic hormones and a regulator of their access to receptors. Albumin also functions as a sink for xenobiotics, diminishing the binding of xenobiotics to hormone receptors and other cellular proteins. This protects animals from endocrine disruption by xenobiotics. We propose that these properties of albumin were important in protochordates and primitive vertebrates, such as jawless fish, about 600 to 530 million years ago, just before and during the Cambrian period. It is at that time that the ancestral receptors of adrenal and sex steroids - androgens, estrogens, glucocorticoids, mineralocorticoids, and progestins - arose in multicellular animals. Albumin regulated access of steroids to their receptors, as well as protecting animals from endocrine disruptors, such as phytochemicals, fungal chemicals and phenolics, and other chemicals formed at hydrothermal vents by geochemical processes. Thus, animals in which albumin expression was high had a selective advantage in regulating the steroid response and avoiding endocrine disruption by xenobiotics.

  15. Quantification of carbamylated albumin in serum based on capillary electrophoresis.

    PubMed

    Delanghe, Sigurd; Moerman, Alena; Pletinck, Anneleen; Schepers, Eva; Glorieux, Griet; Van Biesen, Wim; Delanghe, Joris R; Speeckaert, Marijn M

    2017-09-01

    Protein carbamylation, a nonenzymatic posttranslational modification promoted during uremia, is linked to a poor prognosis. In the present study, carbamylation of serum albumin was assayed using the symmetry factor on a capillary electrophoresis instrument (Helena V8). The symmetry factor has been defined as the distance from the center line of the peak to the back slope, divided by the distance from the center line of the peak to the front slope, with all measurements made at 10% of the maximum peak height. Serum albumin, creatinine, and urea concentrations were assayed using routine methods, whereas uremic toxins were determined using HPLC. In vitro carbamylation induced a marked albumin peak asymmetry. Reference values for the albumin symmetry factor were 0.69-0.92. In kidney patients, albumin peak asymmetry corresponded to the chronic kidney disease stage (p < 0.0001). The symmetry factor correlated well with serum urea (r = -0.5595, p < 0.0001) and creatinine (r = -0.5986, p < 0.0001) concentrations. Several protein-bound uremic toxins showed a significant negative correlation with the symmetry factor. Morphology of the albumin fraction was not affected by presence of glycated albumin and protein-bound antibiotics. In conclusion, the presented method provides a simple, practical way for monitoring protein carbamylation. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Cationized bovine serum albumin with pendant RGD groups forms efficient biocoatings for cell adhesion.

    PubMed

    Ng, Jeck Fei; Weil, Tanja; Jaenicke, Stephan

    2011-11-01

    Cationized bovine serum albumin (cBSA-147) has been modified by attaching the cyclic pentapeptide cRGDfK to its surface through linkers of different length. Coatings of these bioconjugates on glass surfaces were studied for their ability to stimulate cell adhesion. These chemically modified albumins combine a high number of positive charges which facilitate the initial cell adhesion to the surface with multiple Arg-Gly-Asp groups which enable focal adhesion of fibroblast cells by specific interactions with cell-surface receptors. The biocoatings are easily prepared within a few minutes by simple incubation from a dilute solution of the modified albumin. This constitutes a convenient approach for preparing surfaces for cell adhesion. Excellent focal adhesion of NIH 3T3 fibroblast cells on the biocoatings was observed. About 75% of the seeded cells attached to the cRGDfK-cBSA-147 coated surfaces, and 97% of them underwent focal adhesion. Adhering cells were able to grow and proliferate on the coated surfaces, confirming the outstanding biocompatibility of these biocoatings.

  17. Preparation of albumin preferential surfaces on poly(vinyl chloride) membranes via surface self-segregation.

    PubMed

    Ji, Jian; Feng, Linxian; Shen, Jiacong; Barbosa, M A

    2002-08-01

    Poly(vinyl chlorides)-graft-[omega-stearyl-poly(ethylene oxide)] (PVC-g-SPEO), which has a poly(vinyl chloride) (PVC) backbone, poly(ethylene oxide) (PEO) side chain, and stearyl end groups, has been synthesized. Self-organizing blends of the amphiphilic comb polymer in poly(vinyl chlorides) have been examined as a means to create albumin preferential surfaces on polymer films. X-ray photoelectron spectroscopy (XPS) analysis indicates substantial surface segregation of the PVC-g-SPEO. A surface concentration of 59.9 EO wt % is achieved by the solution casting and heat treatment of a film with a bulk concentration of only 3.78 EO wt %. In the aqueous environment, the surface rearrangement of PVC-g-SPEO/PVC blend film is limited and presents a high interfacial energy and high depolar component of interfacial energy due to the "tail-like" SPEO side chain. Protein adsorption tests confirm that PVC-g-SPEO/PVC blend films absorb high levels of albumin and dramatically resist fibrinogen adsorption. Surfaces to attract and reversibly bind albumin, which might diminish the occurrence of thrombosis, inflammation, and infection, are developed by self-organizing blends of the amphiphilic comb polymer in poly(vinyl chlorides).

  18. Chlorpromazine interactions to sera albumins. A study by the quenching of fluorescence

    NASA Astrophysics Data System (ADS)

    Silva, Dilson; Cortez, Célia M.; Louro, Sônia R. W.

    2004-04-01

    Binding of chlorpromazine (CPZ) and hemin (Hmn) to human (HSA) and bovine (BSA) serum albumin was studied by fluorescence quenching technique. Intrinsic fluorescences of BSA and HSA were measured by selectively exciting their tryptophan residues. Gradual quenching was observed by titration of both proteins with CPZ and Hmn. CPZ is a widely used anti-psychosis drug that causes severe side effects and strongly interacts with biomembranes, both in its lipidic and proteic regions. CPZ also interacts with blood components, influences bioavailability, and affects the function of several biomolecules. Albumin plays an important role in the transport and storage of hormones, ions, fatty acids and others substances, including CPZ, affecting the regulation of their plasmatic concentration. Hmn is an important ferric residue of hemoglobin that binds within the hydrophobic region of albumin with great specificity. Hmn added to HSA and BSA solutions at a molar ratio of 1:1 quenched about half of their fluorescence. Stern-Volmer plots obtained from experiments carried out at 25 and 35 °C showed the quenching of fluorescence of HSA and BSA by CPZ to be a collisional phenomenon. Hmn quenches fluorescence by a static process, which specifically indicates the formation of a complex. Our results suggest the prime binding site for CPZ and Hmn on both HSA and BSA to be near tryptophan residues.

  19. Albumin for Prehospital Fluid Resuscitation of Hemorrhagic Shock in Tactical Combat Casualty Care.

    PubMed

    Studer, Nicholas M; April, Michael D; Bowling, F; Danielson, Paul D; Cap, Andrew P

    Optimal fluid resuscitation on the battlefield in the absence of blood products remains unclear. Contemporary Combat medics are generally limited to hydroxyethyl starch or crystalloid solutions, both of which present significant drawbacks. Obtaining US Food and Drug Administration (FDA)-approved freeze-dried plasma (FDP) is a top casualty care research priority for the US Military. Interest in this agent reflects a desire to simultaneously expand intravascular volume and address coagulopathy. The history of FDP dates to the Second World War, when American expeditionary forces used this agent frequently. Also fielded was 25% albumin, an agent that lacks coagulation factors but offers impressive volume expansion with minimal weight to carry and requires no reconstitution in the field. The current potential value of 25% albumin is largely overlooked. Although FDP presents an attractive future option for battlefield prehospital fluid resuscitation once FDA approved, this article argues that in the interim, 25% albumin, augmented with fibrinogen concentrate and tranexamic acid to mitigate hemodilution effects on coagulation capacity, offers an effective volume resuscitation alternative that could save lives on the battlefield immediately. 2017.

  20. Albumin and all-cause mortality risk in insurance applicants.

    PubMed

    Fulks, Michael; Stout, Robert L; Dolan, Vera F

    2010-01-01

    Determine the relationship between albumin levels and all-cause mortality in life insurance applicants. By use of the Social Security Death Master File, mortality was determined in 1,704,566 insurance applicants for whom blood samples were submitted to Clinical Reference Laboratory. There were 53,211 deaths observed in this healthy adult population during a median follow-up of 12 years. Results were stratified by 6 age-sex groups: females: ages 20 to 49, 50 to 69 and 70+; and males: ages 20 to 49, 50 to 69 and 70+. The middle 50% of albumin values specific to each group was used as the reference band for that group. The mortality in bands representing other percentiles of albumin values higher and lower than the middle 50% were compared to the mortality in the reference band for each age-sex group. The highest percentile bands represent the lowest albumin values. Relative risk exceeded 150% of each age- and sex-specific reference band for all groups between the 90th and 95th percentile of albumin values. This translates into 150% risk thresholds at approximately 3.8 mg/dL for all females and for males 70+, and 4.1 mg/dL for males ages 20 to 69. Conversely, the highest 25% of albumin values were associated with approximately a 20% reduction in risk in males and a variable 10% reduction in risk in females when compared to the middle 50% of albumin values. Excluding those with total cholesterol < or = 160 mg/dL, or with AST, GGT or alkaline phosphatase elevations, had little impact on relative risk except at the lowest 0.5% of albumin values. When stratified by age and sex, albumin discriminated between all-cause mortality risks in healthy adults at all ages and across a wide range of values independent of other laboratory tests.

  1. Transfer of oleic acid between albumin and phospholipid vesicles

    SciTech Connect

    Hamilton, J.A.; Cistola, D.P.

    1986-01-01

    The net transfer of oleic acid between egg phosphatidylcholine unilamellar vesicles and bovine serum albumin has been monitored by TC NMR spectroscopy and 90% isotopically substituted (1- TC)oleic acid. The carboxyl chemical shifts of oleic acid bound to albumin were different from those for oleic acid in phospholipid vesicles. Therefore, in mixtures of donor particles, the equilibrium distribution of oleic acid was determined from chemical shift and peak intensity data without separation of donor and acceptor particles. In a system containing equal masses of albumin and phospholipid and a stoichiometry of 4-5 mol of oleic acid per mol of albumin, the oleic acid distribution was pH dependent, with greater than or equal to80% of the oleic acid associated with albumin at pH 7.4; association was greater than or equal to90% at pH 8.0. Decreasing the pH below 7.4 markedly decreased the proportion of fatty acid bound to albumin. The distribution was reversible with pH and was independent of whether vesicles or albumin acted as a donor. These data suggest that pH may strongly influence the partitioning of fatty acid between cellular membranes and albumin. The TC NMR method is also advantageous because it provides information about the structural environments of oleic acid bound to albumin or phospholipid, the ionization state of oleic acid in each environment, and the structural integrity of the vesicles. In addition, minimum and maximum limits for the exchange rates of oleic acid among different environments were obtained from the NMR data.

  2. Gene families encoding isoforms of two major sesame seed storage proteins, 11S globulin and 2S albumin.

    PubMed

    Hsiao, Eric S L; Lin, Li-Jen; Li, Feng-Yin; Wang, Miki M C; Liao, Ming-Yuan; Tzen, Jason T C

    2006-12-13

    Sesame (Sesamum indicum L.) seed has been recognized as a nutritional protein source owing to its richness in methionine. Storage proteins have been implicated in allergenic responses to sesame consumption. Two abundant storage proteins, 11S globulin and 2S albumin, constitute 60-70 and 15-25% of total sesame proteins, respectively. Two gene families separately encoding four 11S globulin and three 2S albumin isoforms were identified in a database search of 3328 expressed sequence tag (EST) sequences from maturing sesame seeds. Full-length cDNA sequences derived from these two gene families were completed by PCR using a maturing sesame cDNA library as the template. The amino acid compositions of these deduced storage proteins revealed that the richness in methionine is attributed mainly to two 2S albumin isoforms and partly to one 11S globulin isoform. The presence of four 11S globulin and three 2S albumin isoforms resolved in SDS-PAGE was confirmed by MALDI-MS analyses. The abundance of these isoforms was in accord with the occurrence frequency of their EST sequences in the database. A comprehensive understanding of these storage proteins at the molecular level may also facilitate the identification of allergens in crude sesame products that have caused severe allergic reactions increasingly reported in the past decade.

  3. Atomic structure and chemistry of human serum albumin

    NASA Technical Reports Server (NTRS)

    He, Xiao M.; Carter, Daniel C.

    1992-01-01

    The three-dimensional structure of human serum albumin has been determined crystallographically to a resolution of 2.8 A. It comprises three homologous domains that assemble to form a heart-shaped molecule. Each domain is a product of two subdomains that possess common structural motifs. The principal regions of ligand binding to human serum albumin are located in hydrophobic cavities in subdomains IIA and ILIA, which exhibit similar chemistry. The structure explains numerous physical phenomena and should provide insight into future pharmacokinetic and genetically engineered therapeutic applications of serum albumin.

  4. Serum albumin concentrations and oedema in the newborn.

    PubMed Central

    Cartlidge, P H; Rutter, N

    1986-01-01

    Serum albumin concentration was measured in 195 infants of 25 to 42 weeks' gestation during the neonatal period. Concentrations were significantly lower in preterm infants, rising from a mean of 19 g/l at 26 weeks to 31 g/l at term. There was a 15% increase in albumin concentrations in the first three weeks of life. Oedema in the early and late neonatal period was common in preterm infants but correlated poorly with hypoalbuminaemia. Measurement of serum albumin concentrations in preterm infants either routinely or because of oedema is not clinically useful. PMID:3740904

  5. Genetic variants of serum albumin in Americans and Japanese

    SciTech Connect

    Madison, J.; Sakamoto, Yasushi; Watkins, S.; Davis, E.; Putnam, F.W. ); Arai, Kunio ); Feld, R.D. ); Kyle R.A. ); Matsuda, Yuhichi; Amaki, Itta )

    1991-11-01

    A collaborative search for albumin genetic variants (alloalbumins) was undertaken by cellulose acetate and agarose electrophoresis at pH 8.6 of the sera of patients at two major medical centers in the United States and of nearly 20,000 blood donors in Japan. Seventeen instances of alloalbuminemia were ascertained, and seven different alloalbumin types were characterized by structural study. Two previously unreported alloalbumin types were identified. All of the variants characterized in this study are point mutants, and the sites are spread throughout the albumin gene. However, about one-fourth of all known albumin mutations are clustered in the sequence segment from position 354 through 382.

  6. Preparation and characterization of albumin nanoparticles encapsulating curcumin intended for the treatment of breast cancer

    PubMed Central

    Jithan, AV; Madhavi, K; Madhavi, M; Prabhakar, K

    2011-01-01

    Introduction: For the real-time clinical utilization of curcumin (an ayurvedic natural product) to treat breast cancer, its dissolution, rate limited solubility, poor tissue absorption, and extensive in vivo metabolism that leads to its poor systemic bioavailability should be overcome. A polymer-based nanoparticle formulation using bovine serum albumin can increase its aqueous solubility and can achieve protected, sustained, and targeted therapy in breast cancer. Materials and Methods: Desolvation technique was optimized for the preparation of albumin nanoparticles. Particle size, drug release, encapsulation efficiency, drug polymer interaction were the in vitro properties that were determined. Cell culture studies, in vivo pharmacokinetics in rats were used for biological characterization of the formulation. Results: The formulations were successfully prepared using 1:1, 1:2, 1:3, 1:4 drug: polymer ratios and the percent entrapment was found to be 74.76%, 91.01%, 85.36%, 86.42%, respectively, and particle size determined by zetasizer was found to be 225.1, 223.5, 226.3, 228.7 nm, respectively, and in vitro release was sustained for at least one month with drug release of 75.74%, 65.97%, 64.42%, 54%, respectively. The dissolution rate and aqueous solubility of curcumin was enhanced with this formulation. Fourier transform infrared spectroscopy (FTIR) studies demonstrated that the drug was not changed in the formulation during the fabrication process. The proliferation assays in MDA-MB-231 tumor cell lines indicated more effectiveness of the formulation compared to its solution form. In rats, albumin nanoparticles sustained drug release, demonstrated more bioavailability, improved pharmacokinetic properties, and enhanced tissue targetability of the drug. Conclusions: An effective curcumin-albumin nanoparticle formulation was successfully developed using a desolvation technique. PMID:23071931

  7. Polynitroxyl albumin and albumin therapy after pediatric asphyxial cardiac arrest: effects on cerebral blood flow and neurologic outcome.

    PubMed

    Manole, Mioara D; Kochanek, Patrick M; Foley, Lesley M; Hitchens, T Kevin; Bayır, Hülya; Alexander, Henry; Garman, Robert; Ma, Li; Hsia, Carleton J C; Ho, Chien; Clark, Robert S B

    2012-03-01

    Postresuscitation cerebral blood flow (CBF) disturbances and generation of reactive oxygen species likely contribute to impaired neurologic outcome after pediatric cardiac arrest (CA). Hence, we determined the effects of the antioxidant colloid polynitroxyl albumin (PNA) versus albumin or normal saline (NS) on CBF and neurologic outcome after asphyxial CA in immature rats. We induced asphyxia for 9 minutes in male and female postnatal day 16 to 18 rats randomized to receive PNA, albumin, or NS at resuscitation from CA or sham surgery. Regional CBF was measured serially from 5 to 150 minutes after resuscitation by arterial spin-labeled magnetic resonance imaging. We assessed motor function (beam balance and inclined plane), spatial memory retention (water maze), and hippocampal neuronal survival. Polynitroxyl albumin reduced early hyperemia seen 5 minutes after CA. In contrast, albumin markedly increased and prolonged hyperemia. In the delayed period after resuscitation (90 to 150 minutes), CBF was comparable among groups. Both PNA- and albumin-treated rats performed better in the water maze versus NS after CA. This benefit was observed only in males. Hippocampal neuron survival was similar between injury groups. Treatment of immature rats with PNA or albumin resulted in divergent acute changes in CBF, but both improved spatial memory retention in males after asphyxial CA.

  8. Hyaluronan secretion into the synovial cavity of rabbit knees and comparison with albumin turnover.

    PubMed Central

    Coleman, P J; Scott, D; Ray, J; Mason, R M; Levick, J R

    1997-01-01

    1. Hyaluronan is not only a lubricant but also enhances the synovial lining's resistance to fluid outflow. This finding led to the proposal that hyaluronan (> 2 x 10(6) Da, approximately 210 nm radius) may escape across the synovial lining less freely than smaller solutes (e.g. albumin, 6.7 x 10(4) Da, 3.6 nm radius) or water. Here multiple washouts were used to measure intraarticular hyaluronan mass and secretion rate in rabbit knees, leading to an estimate of hyaluronan turnover time. Plasma albumin permeation into the joint cavity was also measured to enable comparison of turnover times between molecules of very disparate size. 2. Endogenous hyaluronan mass in the joint cavity, analysed by high performance liquid chromatography of joint washes, was 182 +/- 9.9 micrograms (mean +/- S.E.M; n = 21). Since hyaluronan concentration in synovial fluid averages 3.62 +/- 0.19 micrograms microliters-1, the endogenous synovial fluid volume was calculated to be 50 microliters (mass/concentration), about double the aspiratable volume. 3. The hyaluronan secretion rate over 4 h was 4.80 +/- 0.77 micrograms h-1 (n = 5). The rate was significantly higher in contralateral joints expanded by 2 ml Ringer solution (5.80 +/- 0.84 micrograms h-1, n = 5, P = 0.01, Student's paired t test), indicating a stretch/hydration sensitive secretory mechanism. The newly secreted chains ((2.05-2.48) x 10(6) Da) were not significantly different in length from the endogenous chains (2.95 x 10(6) Da). 4. Hyaluronan turnover time, calculated as mass/secretion rate, was 31.4-37.9 h. This is more than an order of magnitude longer than turnover time for intra-articular albumin. The latter, determined from the intra-articular albumin mass and plasma-to-cavity permeation rate was 1.8 h (95% confidence intervals 1.2-3.5 h, n = 9). The big difference in turnover times support the view that, relative to albumin and water, hyaluronan is partially sieved out and retained in the joint cavity by the synovial

  9. Carbon nanotubes induce secondary structure changes of bovine albumin in aqueous phase.

    PubMed

    Yang, Man; Meng, Jie; Mao, Xiaobo; Yang, Yang; Cheng, Xuelian; Yuan, Hui; Wang, Chen; Xu, Haiyan

    2010-11-01

    Interaction of nanomaterials to protein molecules is one of the most important issues to deeply understand the influences of the nanomaterials upon physiological processes and protein functions. So far most of investigations focused on the protein molecules adsorbed on the nanomaterials surface, less is known about those in the aqueous phase (not absorbed). In this work, luminescent spectroscopy analysis, circular dichroism measurement, atomic force microscopy, matrix-assisted laser desorption/ionization time of flight mass spectrometry, isoelectric focusing and sulfate polyacrylamide gel electrophoresis were used to investigate the influence of oxidized water-soluble multiwalled carbon nanotubes (CNT) dispersing in aqueous solution upon the structures of bovine serum albumin (BSA) through co-incubation. We focused on BSA molecules that stayed in the aqueous phase instead of those adsorbed by CNT. Experimental results show that the fractions of beta-sheet decreased from 33.3% to 29.8% and beta-turn increased from 2% to 5% in reference with native BSA. There was a slight increase of alpha-helix and a slight reduction of random coil. BSA molecules that had been encountered with CNT and were left in the solution formed a loose and flatten morphology on graphite substrates instead of their native tight and round morphology observed by AFM. The value of isoelectric point for BSA after exposed to CNT moved towards to a higher pH position compared with native BSA. All together, it was concluded that the oxidized water-soluble multiwalled carbon nanotubes not only adsorb bovine serum albumin molecules to their surface, but also induces albumin molecules in the aqueous solution undergo secondary structure changes, which lead to a conformation change.

  10. Terlipressin plus albumin versus midodrine and octreotide plus albumin in the treatment of hepatorenal syndrome: A randomized trial.

    PubMed

    Cavallin, Marta; Kamath, Patrick S; Merli, Manuela; Fasolato, Silvano; Toniutto, Pierluigi; Salerno, Francesco; Bernardi, Mauro; Romanelli, Roberto Giulio; Colletta, Cosimo; Salinas, Freddy; Di Giacomo, Antonio; Ridola, Lorenzo; Fornasiere, Ezio; Caraceni, Paolo; Morando, Filippo; Piano, Salvatore; Gatta, Angelo; Angeli, Paolo

    2015-08-01

    Hepatorenal syndrome (HRS), a serious complication of cirrhosis, is associated with high mortality without treatment. Terlipressin with albumin is effective in the reversal of HRS. Where terlipressin is not available, as in the United States, midodrine and octreotide with albumin are used as an alternative treatment of HRS. The aim was to compare the effectiveness of terlipressin plus albumin versus midodrine and octreotide plus albumin in the treatment of HRS in a randomized controlled trial. Twenty-seven patients were randomized to receive terlipressin with albumin (TERLI group) and 22 to receive midodrine and octreotide plus albumin (MID/OCT group). The TERLI group received terlipressin by intravenous infusion, initially 3 mg/24 hours, progressively increased to 12 mg/24 hours if there was no response. The MID/OCT group received midodrine orally at an initial dose of 7.5 mg thrice daily, with the dose increased to a maximum of 12.5 mg thrice daily, together with octreotide subcutaneously: initial dose 100 μg thrice daily and up to 200 μg thrice daily. Both groups received albumin intravenously 1 g/kg of body weight on day 1 and 20-40 g/day thereafter. There was a significantly higher rate of recovery of renal function in the TERLI group (19/27, 70.4%) compared to the MID/OCT group (6/21, 28.6%), P = 0.01. Improvement in renal function and lower baseline Model for End-Stage Liver Disease score were associated with better survival. Terlipressin plus albumin is significantly more effective than midodrine and octreotide plus albumin in improving renal function in patients with HRS. © 2015 by the American Association for the Study of Liver Diseases.

  11. Structural basis of transport of lysophospholipids by human serum albumin

    SciTech Connect

    Guo, Shihui; Shi, Xiaoli; Yang, Feng; Chen, Liqing; Meehan, Edward J.; Bian, Chuanbing; Huang, Mingdong

    2010-10-08

    Lysophospholipids play important roles in cellular signal transduction and are implicated in many biological processes, including tumorigenesis, angiogenesis, immunity, atherosclerosis, arteriosclerosis, cancer and neuronal survival. The intracellular transport of lysophospholipids is through FA (fatty acid)-binding protein. Lysophospholipids are also found in the extracellular space. However, the transport mechanism of lysophospholipids in the extracellular space is unknown. HSA (human serum albumin) is the most abundant carrier protein in blood plasma and plays an important role in determining the absorption, distribution, metabolism and excretion of drugs. In the present study, LPE (lysophosphatidylethanolamine) was used as the ligand to analyse the interaction of lysophospholipids with HSA by fluorescence quenching and crystallography. Fluorescence measurement showed that LPE binds to HSA with a K{sub d} (dissociation constant) of 5.6 {micro}M. The presence of FA (myristate) decreases this binding affinity (K{sub d} of 12.9 {micro}M). Moreover, we determined the crystal structure of HSA in complex with both myristate and LPE and showed that LPE binds at Sudlow site I located in subdomain IIA. LPE occupies two of the three subsites in Sudlow site I, with the LPE acyl chain occupying the hydrophobic bottom of Sudlow site I and the polar head group located at Sudlow site I entrance region pointing to the solvent. This orientation of LPE in HSA suggests that HSA is capable of accommodating other lysophospholipids and phospholipids. The study provides structural information on HSA-lysophospholipid interaction and may facilitate our understanding of the transport and distribution of lysophospholipids.

  12. Albumin (BSA) adsorption onto graphite stepped surfaces

    NASA Astrophysics Data System (ADS)

    Rubio-Pereda, Pamela; Vilhena, J. G.; Takeuchi, Noboru; Serena, Pedro A.; Pérez, Rubén

    2017-06-01

    Nanomaterials are good candidates for the design of novel components with biomedical applications. For example, nano-patterned substrates may be used to immobilize protein molecules in order to integrate them in biosensing units. Here, we perform long MD simulations (up to 200 ns) using an explicit solvent and physiological ion concentrations to characterize the adsorption of bovine serum albumin (BSA) onto a nano-patterned graphite substrate. We have studied the effect of the orientation and step size on the protein adsorption and final conformation. Our results show that the protein is stable, with small changes in the protein secondary structure that are confined to the contact area and reveal the influence of nano-structuring on the spontaneous adsorption, protein-surface binding energies, and protein mobility. Although van der Waals (vdW) interactions play a dominant role, our simulations reveal the important role played by the hydrophobic lipid-binding sites of the BSA molecule in the adsorption process. The complex structure of these sites, that incorporate residues with different hydrophobic character, and their flexibility are crucial to understand the influence of the ion concentration and protein orientation in the different steps of the adsorption process. Our study provides useful information for the molecular engineering of components that require the immobilization of biomolecules and the preservation of their biological activity.

  13. In vivo albumin labeling and lymphatic imaging

    PubMed Central

    Wang, Yu; Lang, Lixin; Huang, Peng; Wang, Zhe; Jacobson, Orit; Kiesewetter, Dale O.; Ali, Iqbal U.; Teng, Gaojun; Niu, Gang; Chen, Xiaoyuan

    2015-01-01

    The ability to accurately and easily locate sentinel lymph nodes (LNs) with noninvasive imaging methods would assist in tumor staging and patient management. For this purpose, we developed a lymphatic imaging agent by mixing fluorine-18 aluminum fluoride-labeled NOTA (1,4,7-triazacyclononane-N,N',N''-triacetic acid)-conjugated truncated Evans blue (18F-AlF-NEB) and Evans blue (EB) dye. After local injection, both 18F-AlF-NEB and EB form complexes with endogenous albumin in the interstitial fluid and allow for visualizing the lymphatic system. Positron emission tomography (PET) and/or optical imaging of LNs was performed in three different animal models including a hind limb inflammation model, an orthotropic breast cancer model, and a metastatic breast cancer model. In all three models, the LNs can be distinguished clearly by the apparent blue color and strong fluorescence signal from EB as well as a high-intensity PET signal from 18F-AlF-NEB. The lymphatic vessels between the LNs can also be optically visualized. The easy preparation, excellent PET and optical imaging quality, and biosafety suggest that this combination of 18F-AlF-NEB and EB has great potential for clinical application to map sentinel LNs and provide intraoperative guidance. PMID:25535368

  14. Albumin (BSA) adsorption onto graphite stepped surfaces.

    PubMed

    Rubio-Pereda, Pamela; Vilhena, J G; Takeuchi, Noboru; Serena, Pedro A; Pérez, Rubén

    2017-06-07

    Nanomaterials are good candidates for the design of novel components with biomedical applications. For example, nano-patterned substrates may be used to immobilize protein molecules in order to integrate them in biosensing units. Here, we perform long MD simulations (up to 200 ns) using an explicit solvent and physiological ion concentrations to characterize the adsorption of bovine serum albumin (BSA) onto a nano-patterned graphite substrate. We have studied the effect of the orientation and step size on the protein adsorption and final conformation. Our results show that the protein is stable, with small changes in the protein secondary structure that are confined to the contact area and reveal the influence of nano-structuring on the spontaneous adsorption, protein-surface binding energies, and protein mobility. Although van der Waals (vdW) interactions play a dominant role, our simulations reveal the important role played by the hydrophobic lipid-binding sites of the BSA molecule in the adsorption process. The complex structure of these sites, that incorporate residues with different hydrophobic character, and their flexibility are crucial to understand the influence of the ion concentration and protein orientation in the different steps of the adsorption process. Our study provides useful information for the molecular engineering of components that require the immobilization of biomolecules and the preservation of their biological activity.

  15. Photophysical investigations of squaraine and cyanine dyes and their interaction with bovine serum albumin

    NASA Astrophysics Data System (ADS)

    Saikiran, M.; Sato, D.; Pandey, S. S.; Kato, T.

    2016-04-01

    A model far-red sensitive symmetrical squaraine dye (SQ-3) and unsymmetrical near infra-red sensitive cyanine dye (UCD-1) bearing direct-COOH functionalized indole ring were synthesized, characterized and subjected to photophysical investigations including their interaction with bovine serum albumin (BSA) as a model protein in phosphate buffer solution (PBS). Both of the dyes exhibit strong interaction with BSA in phosphate buffer with high apparent binding constant. A judicious tuning of hydrophobic main backbone with reactive functionality for associative interaction with active site of BSA has been found to be necessary for BSA detection in PBS.

  16. On the interaction of luminol with human serum albumin: Nature and thermodynamics of ligand binding

    NASA Astrophysics Data System (ADS)

    Moyon, N. Shaemningwar; Mitra, Sivaprasad

    2010-09-01

    The mechanism and thermodynamic parameters for the binding of luminol (LH 2) with human serum albumin was explored by steady state and picosecond time-resolved fluorescence spectroscopy. It was shown that out of two possible LH 2 conformers present is solution, only one is accessible for binding with HSA. The thermodynamic parameters like enthalpy (Δ H) and entropy (Δ S) change corresponding to the ligand binding process were also estimated by performing the experiment at different temperatures. The ligand replacement experiment with bilirubin confirms that LH 2 binds into the sub-domain IIA of the protein.

  17. EPR study of the effect of terahertz radiation on the albumin conformation dynamics

    NASA Astrophysics Data System (ADS)

    Nemova, Eugenia F.; Cherkasova, Olga P.; Fedorov, Vyacheslav I.

    2010-09-01

    Effect of the preliminary irradiation of bovine serum albumin (BSA) in the terahertz spectral range on the conformation changes revealed with the help of EPR spectroscopy was investigated using the spin probing technique. The formation of the spin probe occurs directly in the aqueous solution of BSA from a nitrone compound (dihydropyrazine dioxide). It was shown that irradiation causes changes in the parameters of the EPR spectrum of the spin probe. An approach to linking the observed changes with the structural characteristics of reaction centres - the functional groups of amino acids comprising BSA - was outlined.

  18. Triplet-triplet energy transfer between luminescent probes bound to albumins

    NASA Astrophysics Data System (ADS)

    Mel'Nikov, A. G.; Saletskii, A. M.; Kochubey, V. I.; Pravdin, A. B.; Kurchatov, I. S.; Mel'Nikov, G. V.

    2010-08-01

    The interaction of polar and nonpolar luminescent probes with human blood serum albumins is studied by absorption and luminescence spectroscopy. It is found that the probes (polar eosin and nonpolar anthracene) can efficiently bind to proteins. The radii of the quenching spheres of energy-donor (eosin) triplet states in the presence of an acceptor (anthracene) in the process of the triplet-triplet energy transfer in proteins are determined for homogeneous and inhomogeneous distributions of acceptor molecules over the solution volume. It is shown that a decrease in the radius of the quenching sphere observed upon the addition of sodium dodecylsulfate surfactant is caused by structural changes in the protein.

  19. Enantiomeric separations using bovine serum albumin immobilized on ion-exchange stationary phases

    SciTech Connect

    Jacobson, S.C.; Guiochon, G. |

    1992-07-01

    Bovine serum albumin (BSA) can be readily immobilized on ion-exchange stationary phases by frontal analysis of a proper solution. This provides a simple means of adjusting the amount of BSA contained in the column and of measuring it accurately. Although the immobilization is ionic and not covalent, the columns are stable for extensive periods of time. If needed, they can be easily regenerated by the same frontal analysis procedure. Results for the separation of various organic compounds on these columns are reported. 11 refs., 3 figs., 2 tabs.

  20. Urinary Albumin Detection: Comparison of Two Different Methods.

    PubMed

    Molinario, Rossana; Pocino, Krizia; Daloiso, Pio Dante; Giannace, Angela; Spirito, Giulia; Zuppi, Cecilia; Antenucci, Mirca

    2016-11-01

    Monitoring urinary albumin is a useful method in clinical practice for the management of diabetic nephropathy, chronic kidney disease, and hypertension. Currently there are neither standardized methods nor reference material for the determination of urinary albumin; for this reason it is useful to compare different assays used in clinical laboratory. The aim of this study is to verify analytical performance of an immunoturbidimetric assay on Roche Cobas 8000 platform and to compare urinary albumin results with those obtained by immunonephelometry on Siemens Dade Behring BN II Nephelometer. The method comparison showed a good linear relationship, confirmed by Passing-Bablok and Bland-Altman plots. The turbidimetric assay meets the requirements of accuracy and precision for the practice of medical diagnostics and clinical use. The present study can contribute to the methods standardization and harmonization of urinary albumin assay. © 2016 Wiley Periodicals, Inc.

  1. Distribution of chylomicrons and albumin in dog kidney

    PubMed Central

    Pinter, G. G.

    1967-01-01

    1. Under specified experimental conditions the distribution space of labelled chylomicrons in the kidney was 13·8 ± 0·9 ml./100 g. tissue. The assumption is supported that this provides a measure for the quantity of intravascular plasma constituents. 2. Values for red blood cells and albumin distribution spaces were 5·2 ± 0·6 and 20·2 ± 1·0 ml./100 g tissue, respectively, in the whole kidney. The ratio of tissue haematocrit over simultaneous arterial haematocrit averaged 0·56. The extravascular albumin fraction amounted to about 31·0% of the total albumin in the whole kidney. 3. A statistically significant correlation was demonstrated between osmotic urine/plasma (U/P) ratios (within the approximate limits of 0·6-1·8) and quantities of extravascular albumin in the medulla. PMID:6059001

  2. Dielectric properties of albumin and yolk of avian egg.

    PubMed

    Lokhande, M P; Arbad, B R; Landge, M G; Mehrotra, S C

    1996-04-01

    The dielectric properties of albumin and yolk of eggs of hen and duck have been investigated using the time domain reflectometry (TDR) technique in the frequency range 10 MHz to 10 GHz at room temperature. The conductivity and pH values were also measured. It has been found that the values of dielectric constant (epsilon s) is lower, while the values of relaxation time tau(ps) are higher than that of pure water possibly due to the bound water present in the yolk and albumin of the avian egg. The dielectric constant for albumin is more than that for yolk of eggs, while reverse is found with the values of relaxation time. Also albumin shows approximately three times higher conductivity than that of yolk. In the case of relatively older (by 2 days) eggs, the dielectric parameters tend to be slightly increased.

  3. Exercise improves albumin fractional synthetic rate in chronic hemodialysis patients.

    PubMed

    Pupim, L B; Flakoll, P J; Ikizler, T A

    2007-05-01

    To determine whether exercise augments the improvements in fractional synthetic rate (FSR) of albumin observed with nutrition alone. Randomized crossover study. Each patient randomly participated in two protein metabolism kinetic studies using primed-constant infusion of (13C) leucine 2 h before, during and 2 h after hemodialysis. Plasma enrichments of (13C) leucine and (13C) ketoisocaproate were examined to determine the FSR of albumin. General Clinical Research Center at Vanderbilt University Medical Center. Five chronic hemodialysis (CHD) patients. Intra-dialytic parenteral nutrition (IDPN) with or without exercise. Exercise performance during hemodialysis significantly improves the FSR of albumin beyond what is observed with IDPN alone (26.2+/-3.1% per day versus 17.7+/-1.9% per day, P<0.05). Exercise improves albumin fractional synthetic rate beyond what is observed with IDPN alone in the acute setting in CHD patients.

  4. 99M-technetium labeled macroaggregated human serum albumin pharmaceutical

    DOEpatents

    Winchell, Harry S.; Barak, Morton; Van Fleet, III, Parmer

    1977-05-17

    A reagent comprising macroaggregated human serum albumin having dispersed therein particles of stannous tin and a method for instantly making a labeled pharmaceutical therefrom, are disclosed. The labeled pharmaceutical is utilized in organ imaging.

  5. Packing density of the PEG-shell in PEG-albumins: PEGylation induced viscosity and COP are inverse correlate of packing density.

    PubMed

    Ananda, K; Manjula, Belur N; Meng, Fantao; Acharya, Vivek N; Intaglietta, Marcos; Acharya, Seetharama A

    2012-02-01

    PEG-Alb represents a new class of low viscogenic plasma expanders that achieve super perfusion in vivo by mimicking the vasodilatory influence of high viscogenic plasma expanders. PEGylation-engineered structure of PEG albumin can be envisaged as a deformable molecular domain around the rigid central protein core. The correlation between the structure of PEG-shell in terms of packing of the PEG inside the PEG shell and PEGylation induced plasma expander (PE)-like properties of albumin has been investigated as a function of the number and length of the PEG-chain. The increase in molecular radius of albumin on PEGylation is non-linear as a function of the number of PEG chains conjugated. The packing density of PEG within the PEG-shell is an inverse correlate of PEG-chain size; i.e. the shorter chains pack more compactly than the longer ones. The PEGylation induced increase in the viscosity and COP of albumin is an exponential correlation of the number of ethylene oxide units (-CH(2)-CH(2)-O-) conjugated and is also a function of the PEG-chain length. At equivalence of PEG mass conjugated, the viscosity and COP of PEG-albumin adducts correlate inversely with packing density of PEG. All PEGylated albumins are not equivalent on the basis of total PEG mass conjugated. Accordingly, the structure of PEG albumin and its solution properties can be engineered to optimize a given total PEG mass for the application of PEG albumin as a resuscitation fluid. The extension arms minimize the influence of PEG shell on the structure of the protein core. We speculate that EAF-PEGylation is a preferable platform for PEGylation of protein therapeutics and is expected to generate products with better therapeutic efficacy.

  6. Preparation of Bovine Serum Albumin (BSA) nanoparticles by desolvation using a membrane contactor: a new tool for large scale production.

    PubMed

    Yedomon, B; Fessi, H; Charcosset, C

    2013-11-01

    Albumin nanoparticles are attractive drug delivery systems as they can be prepared under soft conditions and incorporate several kinds of molecules. The aim of this study was to upscale the desolvation process for preparing Bovine Serum Albumin (BSA) nanoparticles using a membrane contactor. At a first step, the BSA nanoparticles were prepared at small scale using a syringe pump. BSA nanoparticles of 139 nm in size, with a polydispersity index of 0.046, were obtained at the optimal conditions: pH 8.2, 100 mg mL(-1) BSA albumin solution (2 mL), and 1 mL min(-1) flow rate of ethanol addition (8 mL). The upscaling with a membrane contactor was achieved by permeating ethanol through the pores of a Shirasu Porous Glass (SPG Technology Co., Japan) membrane and circulating the aqueous phase tangentially to the membrane surface. By increasing the pressure of the ethanol from 1 to 2.7 bars, a progressive decrease in nanoparticle size was obtained with a high nanoparticles yield (around 94-96%). In addition, the flow rate of the circulating phase did not affect the BSA nanoparticle characteristics. At the optimal conditions (pH 8.2, 100 mg mL(-1) BSA albumin solution, pressure of ethanol 2.7 bars, flow rate of the circulating phase 30.7 mL s(-1)), the BSA nanoparticles showed similar characteristics to those obtained with the syringe pump. Large batches of BSA nanoparticles were prepared up to 10 g BSA. The BSA nanoparticles were stable at least during 2 months at 4 °C, and their characteristics were reproducible. It was then concluded that the membrane contactor technique could be a suitable method for the preparation of albumin nanoparticles at large scale with properties similar to that obtained at small scale.

  7. Effects of saline or albumin resuscitation on standard coagulation tests.

    PubMed

    Bellomo, Rinaldo; Morimatsu, Hiroshi; Presneill, Jeff; French, Craig; Cole, Louise; Story, David; Uchino, Shigehiko; Naka, Toshio; Finfer, Simon; Cooper, D James; Myburgh, John

    2009-12-01

    To explore whether fluid resuscitation with normal saline or 4% albumin is associated with differential changes in routine clinical coagulation tests. Substudy from a large double-blind randomised controlled trial, the SAFE (Saline versus Albumin Fluid Evaluation) study. Three general intensive care units. Cohort of 687 critically ill patients. We randomly allocated patients to receive either 4% human albumin or normal saline for fluid resuscitation, and collected demographic and haematological data. Albumin was administered to 338 patients and saline to 349. At baseline, the two groups had similar mean activated partial thromboplastin time (APTT) of 37.2 s (albumin) v 39.1 s (saline); mean international normalised ratio (INR) of 1.38 v 1.34, and mean platelet count of 244 x 10(9)/L v 249 x 10(9)/L. After randomisation, during the first day of treatment, the APTT in the albumin group was prolonged by a mean of 2.7 s, but shortened slightly by a mean of -0.9 s in the saline group. The INR did not change in either group, while the platelet count decreased transiently in both groups. Using multivariate analysis of covariance to account for baseline coagulation status, albumin fluid resuscitation (P = 0.01) and a greater overall volume of resuscitation (P = 0.03) were independently associated with prolongation of APTT during the first day. Administration of albumin or of larger fluid volumes is associated with a prolongation of APTT. In ICU patients, the choice and amount of resuscitation fluid may affect a routinely used coagulation test.

  8. Albumin Antioxidant Response to Stress in Diabetic Nephropathy Progression

    PubMed Cent