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Sample records for albumin total bilirubin

  1. Bilirubin Binding Capacity in the Preterm Neonate.

    PubMed

    Amin, Sanjiv B

    2016-06-01

    Total serum/plasma bilirubin (TB), the biochemical measure currently used to evaluate and manage hyperbilirubinemia, is not a useful predictor of bilirubin-induced neurotoxicity in premature infants. Altered bilirubin-albumin binding in premature infants limits the usefulness of TB in premature infants. In this article, bilirubin-albumin binding, a modifying factor for bilirubin-induced neurotoxicity, in premature infants is reviewed. PMID:27235205

  2. Circular dichroism study of the interaction between mutagens and bilirubin bound to different binding sites of serum albumins.

    PubMed

    Orlov, Sergey; Goncharova, Iryna; Urbanová, Marie

    2014-05-21

    Although recent investigations have shown that bilirubin not only has a negative role in the organism but also exhibits significant antimutagenic properties, the mechanisms of interactions between bilirubin and mutagens are not clear. In this study, interaction between bilirubin bound to different binding sites of mammalian serum albumins with structural analogues of the mutagens 2-aminofluorene, 2,7-diaminofluorene and mutagen 2,4,7-trinitrofluorenone were investigated by circular dichroism and absorption spectroscopy. Homological human and bovine serum albumins were used as chiral matrices, which preferentially bind different conformers of bilirubin in the primary binding sites and make it observable by circular dichroism. These molecular systems approximated a real system for the study of mutagens in blood serum. Differences between the interaction of bilirubin bound to primary and to secondary binding sites of serum albumins with mutagens were shown. For bilirubin bound to secondary binding sites with low affinity, partial displacement and the formation of self-associates were observed in all studied mutagens. The associates of bilirubin bound to primary binding sites of serum albumins are formed with 2-aminofluorene and 2,4,7-trinitrofluorenone. It was proposed that 2,7-diaminofluorene does not interact with bilirubin bound to primary sites of human and bovine serum albumins due to the spatial hindrance of the albumins binding domains. The spatial arrangement of the bilirubin bound to serum albumin along with the studied mutagens was modelled using ligand docking, which revealed a possibility of an arrangement of the both bilirubin and 2-aminofluorene and 2,4,7-trinitrofluorenone in the primary binding site of human serum albumin. PMID:24589992

  3. Synthesis and characterization of a biospecific adsorbent containing bovine serum albumin as a ligand and its use for bilirubin retention.

    PubMed

    Alvarez, C; Strumia, M; Bertorello, H

    2001-10-30

    Epoxy-activated gels from cross-linked polybutadiene-hydroxyethylmethacrylate (PB-HEMA) copolymer and epichlorohydrin (ECH) were prepared and characterized. Albumin was covalently bonded to the matrix and used as support of affinity chromatography in bilirubin (BR) retention experiments. PB-HEMA-ECH with different amounts of immobilized albumin (between 5.20 and 6.80 mg/g dry gel) were obtained. Bilirubin retention of 3.10 mg/g of these beads was observed at 5 degrees C. PMID:11694308

  4. Correlation Between C-reactive Protein and Non-enzymatic Antioxidants (Albumin, Ferritin, Uric Acid and Bilirubin) in Hemodialysis Patients

    PubMed Central

    Beciragic, Amela; Resic, Halima; Prohic, Nejra; Karamehic, Jasenko; Smajlovic, Ajdin; Masnic, Fahrudin; Ajanovic, Selma; Coric, Aida

    2015-01-01

    Introduction: Increased levels of C-Reactive Protein are found in 30-60% on hemodialysis patients and it is closely associated with the progression of atherosclerosis, cardiovascular morbidity and mortality. Non enzymatic antioxidants are antioxidants which primarily retain potentially dangerous ions of iron and copper in their inactive form and thereby prevent its participation in the production of free radicals. Aim: The aim of the study was to examine the relationship of CRP and non enzymatic antioxidants (albumin, ferritin, uric acid and bilirubin) i.e. examine the importance of CRP as a serum biomarker in assessing the condition of inflammation and its relationship to antioxidant protection in patients on hemodialysis. Methods: The study was cross-sectional, clinical, comparative and descriptive. The study involved 100 patients (non diabetic) on chronic hemodialysis. The control group consisted of 50 subjects without subjective and objective indicators of chronic renal disease. In all patients, the concentration of CRP as well as concentrations of non enzymatic antioxidants were determined. Results: In the group of hemodialysis patients 60% were men and 40% women. The average age of hemodialysis patients was 54.13 ± 11.8 years and the average age of the control group 41.72 ± 9.8 years. The average duration of hemodialysis treatment was 91.42 ± 76.2 months. In the group of hemodialysis patients statistically significant, negative linear correlation was determined between the concentration of CRP in and albumin concentration (rho = -0.251, p = 0.012) as well as negative, statistics insignificant, linear correlation between serum CRP and the concentration of uric acid (r = -0.077, p = 0.448). Furthermore, the positive, linear correlation was determined between serum CRP and ferritin (r = 0.159, p = 0.114) and positive linear correlation between CRP and total serum bilirubin (r = 0.121, p = 0.230). In the control group was determined a statistically significant

  5. Analysis of binding ability of two tetramethylpyridylporphyrins to albumin and its complex with bilirubin.

    PubMed

    Solomonov, Alexey V; Shipitsyna, Maria K; Vashurin, Arthur S; Rumyantsev, Evgeniy V; Timin, Alexander S; Ivanov, Sergey P

    2016-11-01

    An interaction between 5,10,15,20-tetrakis-(N-methyl-x-pyridyl)porphyrins, x=2; 4 (TMPyPs) with bovine serum albumin (BSA) and its bilirubin (BR) complex was investigated by UV-Viz and fluorescence spectroscopy under imitated physiological conditions involving molecular docking studies. The parameters of forming intermolecular complexes (binding constants, quenching rate constants, quenching sphere radius etc.) were determined. It was showed that the interaction between proteins and TMPyPs occurs via static quenching of protein fluorescence and has predominantly hydrophobic and electrostatic character. It was revealed that obtained complexes are relatively stable, but in the case of TMPyP4 binding with proteins occurs better than TMPyP2. Nevertheless, both TMPyPs have better binding ability with free protein compared to BRBSA at the same time. The influence of TMPyPs on the conformational changes in protein molecules was studied using synchronous fluorescence spectroscopy. It was found that there is no competition of BR with TMPyPs for binging sites on protein molecule and BR displacement does not occur. Molecular docking calculations have showed that TMPyPs can bind with albumin via tryptophan residue in the hydrophilic binding site of protein molecule but it is not one possible interaction way. PMID:27267279

  6. 21 CFR 862.1113 - Bilirubin (total and unbound) in the neonate test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1113 Bilirubin (total and unbound) in the neonate test system....

  7. 21 CFR 862.1113 - Bilirubin (total and unbound) in the neonate test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1113 Bilirubin (total and unbound) in the neonate test system....

  8. 21 CFR 862.1113 - Bilirubin (total and unbound) in the neonate test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1113 Bilirubin (total and unbound) in the neonate test system....

  9. 21 CFR 862.1113 - Bilirubin (total and unbound) in the neonate test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1113 Bilirubin (total and unbound) in the neonate test system....

  10. 21 CFR 862.1113 - Bilirubin (total and unbound) in the neonate test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1113 Bilirubin (total and unbound) in the neonate test system....

  11. Total Protein and Albumin/Globulin Ratio Test

    MedlinePlus

    ... limited. Home Visit Global Sites Search Help? Total Protein and Albumin/Globulin (A/G) Ratio Share this ... Globulin Ratio; A/G Ratio Formal name: Total Protein; Albumin to Globulin Ratio Related tests: Albumin ; Liver ...

  12. Characterization of erythrosine B binding to bovine serum albumin and bilirubin displacement.

    PubMed

    Mathavan, Vinodaran M K; Boh, Boon Kim; Tayyab, Saad

    2009-08-01

    The interaction of crythrosine B (ErB), a commonly used dye for coloring foods and drinks, with bovine scrum albumin (BSA) was investigated both in the absence and presence of bilirubin (BR) using absorption and absorption difference spectroscopy. ErB binding to BSA was reflected from a significant red shift of 11 nm in the absorption maximum of ErB (527 nm) with the change in absorbance at lamdamax. Analysis of absorption difference spectroscopic titration results of BSA with increasing concentrations of ErB3 using Benesi-Hildebrand equation gave the association constant, K as 6.9 x 10(4) M(-1). BR displacing action of ErB was revealed by a significant blue shift in the absorption maximum, accompanied by a decrease in absorbance difference at lamdamax in the difference spectrum of BR-BSA complex upon addition of increasing concentrations of ErB. This was further substantiated by fluorescence spectroscopy, as addition of increasing concentrations of ErB to BR-BSA complex caused a significant decrease in fluoresccnce at 510 nm. The results suggest that ErB binds to a site in the vicinity of BR binding site on BSA. Therefore, intake of ErB may increase the risk of hyperbilirubinemia in the healthy subjects. PMID:19788065

  13. Clinical assessment of bilirubin-induced neurotoxicity in premature infants.

    PubMed

    Amin, Sanjiv B

    2004-10-01

    The clinical assessment of bilirubin-induced neurotoxicity in premature infants remains difficult in the absence of a gestational age-specific total or free (unbound) bilirubin level that predicts bilirubin-induced neurotoxicity. Because the total serum bilirubin concentration is an unreliable predictor of bilirubin-induced neurotoxicity in premature infants, alternative mean for predicting bilirubin-induced neurotoxicity in jaundiced preterm newborns is needed. Over the last few years, we have witnessed substantial gain in our knowledge involving usefulness of bilirubin-binding variables (total bilirubin, free bilirubin, bilirubin:albumin molar ratio) for clinical assessment of bilirubin-induced neurotoxicity in preterm infants. The knowledge gained has provided impetus for more clinical studies that are geared toward confirming the usefulness of free bilirubin as a predictor of bilirubin-induced neurotoxicity and identifying the gestational age-specific free bilirubin level that may increase the risk of bilirubin-induced neurotoxicity in premature infants. The paper has attempted to provide an overview of bilirubin-induced auditory toxicity along with the existing clinical evidence in favor of free bilirubin assay and usefulness of auditory brainstem evoked response for evaluation of bilirubin-induced neurotoxicity in premature infants. In addition, the author has described findings that suggest an association of apnea, a clinical manifestation, with acute bilirubin encephalopathy in premature infants. PMID:15686265

  14. Comparison of transcutaneous and total serum bilirubin measurement in Turkish newborns.

    PubMed

    Şimşek, Fatih Mehmet; Narter, Fatma; Ergüven, Müferet

    2014-01-01

    Severe neonatal hyperbilirubinemia can be prevented by screening for neonatal jaundice. Transcutaneous bilirubin (TcB) measurement is a noninvasive method for screening neonates. The aim of this study was to examine the correlation between TcB measurement (using the JM-103 bilirubinometer) and total serum bilirubin (TSB) measurement. To our knowledge, this is the first study evaluating the usefulness of the JM-103 bilirubinometer in Turkish neonates. Two hundred and fifty healthy infants in our well-baby nurseries and follow-up clinic with a gestational age of ≥36 weeks who were ≤15 days old were enrolled in this study. TcB measurements were taken usinng the JM-103; almost simultaneously, TSB was checked using a spectrophotometric method. The mean±SD TSB level was 11.2±4.6 mg/dl (range, 0.9-27.0 mg/dl); 17.2% of cases had TSB>15 mg/dl. There was good correlation between transcutaneous bilirubin and total serum bilirubin measurements (Pearson's correlation coefficient 0.87 for TcB from the forehead, 0.88 for TcB from the sternum; p<0.001). The transcutaneous bilirubin measurement tended to underestimate the value with increasing discrepancy at higher TSB values. The mean difference between serum bilirubin and transcutaneous (from the sternum and forehead) bilirubin values was significantly lower in cases not requiring phototherapy than in those requiring phototherapy [2.6 mg/dl (sternum) vs 4.8 mg/dl, 2.9 mg/dl (forehead) vs. 5.2 mg/dl, respectively; p<0.001] Although the JM-103 bilirubinometer tends to underestimate serum bilirubin, especially in patients with high bilirubin levels, it is a suitable screening tool to identify jaundiced infants that require a serum bilirubin check and may reduce the need for TSB measurements. PMID:26388591

  15. Serum total bilirubin levels and coronary heart disease--Causal association or epiphenomenon?

    PubMed

    Kunutsor, Setor K

    2015-12-01

    Observational epidemiological evidence supports a linear inverse and independent association between serum total bilirubin levels and coronary heart disease (CHD) risk, but whether this association is causal remains to be ascertained. A Mendelian randomization approach was employed to test whether serum total bilirubin is causally linked to CHD. The genetic variant rs6742078--well known to specifically modify levels of serum total bilirubin and accounting for up to 20% of the variance in circulating serum total bilirubin levels--was used as an instrumental variable. In pooled analysis of estimates reported from published genome-wide association studies, every copy of the T allele of rs6742078 was associated with 0.42 standard deviation (SD) higher levels of serum total bilirubin (95% confidence interval, 0.40 to 0.43). Based on combined data from the Coronary Artery Disease Genome wide Replication and Meta-analyses and the Coronary Artery Disease (C4D) Genetics Consortium involving a total of 36,763 CHD cases and 76,997 controls, the odds ratio for CHD per copy of the T allele was 1.01 (95% confidence interval, 0.99 to 1.04). The odds ratio of CHD for a 1 SD genetically elevated serum total bilirubin level was 1.03 (95% confidence interval, 0.98 to 1.09). The current findings casts doubt on a strong causal association of serum total bilirubin levels with CHD. The inverse associations demonstrated in observational studies may be driven by biases such as unmeasured confounding and/or reverse causation. However, further research in large-scale consortia is needed. PMID:26408227

  16. The Bilirubin Albumin Ratio in the Management of Hyperbilirubinemia in Preterm Infants to Improve Neurodevelopmental Outcome: A Randomized Controlled Trial – BARTrial

    PubMed Central

    van Imhoff, Deirdre E.; Bos, Arend F.; Lopriore, Enrico; Offringa, Martin; Ruiter, Selma A. J.; van Braeckel, Koen N. J. A.; Krabbe, Paul F. M.; Quik, Elise H.; van Toledo-Eppinga, Letty; Nuytemans, Debbie H. G. M.; van Wassenaer-Leemhuis, Aleid G.; Benders, Manon J. N.; Korbeeck-van Hof, Karen K. M.; van Lingen, Richard A.; Groot Jebbink, Liesbeth J. M.; Liem, Djien; Mansvelt, Petri; Buijs, Jan; Govaert, Paul; van Vliet, Ineke; Mulder, Twan L. M.; Wolfs, Cecile; Fetter, Willem P. F.; Laarman, Celeste

    2014-01-01

    Background and Objective High bilirubin/albumin (B/A) ratios increase the risk of bilirubin neurotoxicity. The B/A ratio may be a valuable measure, in addition to the total serum bilirubin (TSB), in the management of hyperbilirubinemia. We aimed to assess whether the additional use of B/A ratios in the management of hyperbilirubinemia in preterm infants improved neurodevelopmental outcome. Methods In a prospective, randomized controlled trial, 615 preterm infants of 32 weeks' gestation or less were randomly assigned to treatment based on either B/A ratio and TSB thresholds (consensus-based), whichever threshold was crossed first, or on the TSB thresholds only. The primary outcome was neurodevelopment at 18 to 24 months' corrected age as assessed with the Bayley Scales of Infant Development III by investigators unaware of treatment allocation. Secondary outcomes included complications of preterm birth and death. Results Composite motor (100±13 vs. 101±12) and cognitive (101±12 vs. 101±11) scores did not differ between the B/A ratio and TSB groups. Demographic characteristics, maximal TSB levels, B/A ratios, and other secondary outcomes were similar. The rates of death and/or severe neurodevelopmental impairment for the B/A ratio versus TSB groups were 15.4% versus 15.5% (P = 1.0) and 2.8% versus 1.4% (P = 0.62) for birth weights ≤1000 g and 1.8% versus 5.8% (P = 0.03) and 4.1% versus 2.0% (P = 0.26) for birth weights of >1000 g. Conclusions The additional use of B/A ratio in the management of hyperbilirubinemia in preterm infants did not improve their neurodevelopmental outcome. Trial Registration Controlled-Trials.com ISRCTN74465643 PMID:24927259

  17. A Genome-Wide Association Study of Total Bilirubin and Cholelithiasis Risk in Sickle Cell Anemia

    PubMed Central

    Milton, Jacqueline N.; Sebastiani, Paola; Solovieff, Nadia; Hartley, Stephen W.; Bhatnagar, Pallav; Arking, Dan E.; Dworkis, Daniel A.; Casella, James F.; Barron-Casella, Emily; Bean, Christopher J.; Hooper, W. Craig; DeBaun, Michael R.; Garrett, Melanie E.; Soldano, Karen; Telen, Marilyn J.; Ashley-Koch, Allison; Gladwin, Mark T.; Baldwin, Clinton T.; Steinberg, Martin H.; Klings, Elizabeth S.

    2012-01-01

    Serum bilirubin levels have been associated with polymorphisms in the UGT1A1 promoter in normal populations and in patients with hemolytic anemias, including sickle cell anemia. When hemolysis occurs circulating heme increases, leading to elevated bilirubin levels and an increased incidence of cholelithiasis. We performed the first genome-wide association study (GWAS) of bilirubin levels and cholelithiasis risk in a discovery cohort of 1,117 sickle cell anemia patients. We found 15 single nucleotide polymorphisms (SNPs) associated with total bilirubin levels at the genome-wide significance level (p value <5×10−8). SNPs in UGT1A1, UGT1A3, UGT1A6, UGT1A8 and UGT1A10, different isoforms within the UGT1A locus, were identified (most significant rs887829, p = 9.08×10−25). All of these associations were validated in 4 independent sets of sickle cell anemia patients. We tested the association of the 15 SNPs with cholelithiasis in the discovery cohort and found a significant association (most significant p value 1.15×10−4). These results confirm that the UGT1A region is the major regulator of bilirubin metabolism in African Americans with sickle cell anemia, similar to what is observed in other ethnicities. PMID:22558097

  18. 21 CFR 862.1110 - Bilirubin (total or direct) test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Bilirubin (total or direct) test system. 862.1110 Section 862.1110 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry...

  19. 21 CFR 862.1110 - Bilirubin (total or direct) test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Bilirubin (total or direct) test system. 862.1110 Section 862.1110 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry...

  20. 21 CFR 862.1110 - Bilirubin (total or direct) test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Bilirubin (total or direct) test system. 862.1110 Section 862.1110 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry...

  1. 21 CFR 862.1110 - Bilirubin (total or direct) test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Bilirubin (total or direct) test system. 862.1110 Section 862.1110 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry...

  2. 21 CFR 862.1110 - Bilirubin (total or direct) test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Bilirubin (total or direct) test system. 862.1110 Section 862.1110 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry...

  3. Human serum albumin-stabilized gold nanoclusters act as an electron transfer bridge supporting specific electrocatalysis of bilirubin useful for biosensing applications.

    PubMed

    Santhosh, Mallesh; Chinnadayyala, Somasekhar R; Singh, Naveen K; Goswami, Pranab

    2016-10-01

    Human serum albumin (HSA)-stabilized Au18 nanoclusters (AuNCs) were synthesized and chemically immobilized on an Indium tin oxide (ITO) plate. The assembly process was characterized by advanced electrochemical and spectroscopic techniques. The bare ITO electrode generated three irreversible oxidation peaks, whereas the HSA-AuNC-modified electrode produced a pair of redox peaks for bilirubin at a formal potential of 0.27V (vs. Ag/AgCl). However, the native HSA protein immobilized on the ITO electrode failed to produce any redox peak for bilirubin. The results indicate that the AuNCs present in HSA act as electron transfer bridge between bilirubin and the ITO plate. Docking studies of AuNC with HSA revealed that the best docked structure of the nanocluster is located around the vicinity of the bilirubin binding site, with an orientation that allows specific oxidation. When the HSA-AuNC-modified electrode was employed for the detection of bilirubin using chronoamperometry at 0.3V (vs. Ag/AgCl), a steady-state current response against bilirubin in the range of 0.2μM to 7μM, with a sensitivity of 0.34μAμM(-1) and limit of detection of 86.32nM at S/N 3, was obtained. The bioelectrode was successfully applied to measure the bilirubin content in spiked serum samples. The results indicate the feasibility of using HSA-AuNC as a biorecognition element for the detection of serum bilirubin levels using an electrochemical technique. PMID:27126550

  4. High baseline bilirubin and low albumin predict liver decompensation and serious adverse events in HCV-infected patients treated with sofosbuvir-containing regimens.

    PubMed

    Perumalswami, P V; Patel, N; Bichoupan, K; Ku, L; Yalamanchili, R; Harty, A; Motamed, D; Khaitova, V; Chang, C; Grewal, P; Liu, L; Schiano, T D; Woodward, M; Dieterich, D T; Branch, A D

    2016-09-01

    To conduct surveillance and determine the safety profile of new hepatitis C virus treatments in real-world clinical practice. Hepatic decompensation and other serious adverse events were investigated in an observational cohort study of 511 patients treated with regimens containing sofosbuvir, December 2013-June 2014. Among 499 previously stable patients (no history of hepatic decompensation during the previous 12 months), a nested case-control study was performed to identify predictors of decompensation/serious adverse event. Cases and controls were matched 1:5 based on treatment regimen and duration. Matched conditional logistic regression was used for analysis. Providers scored the likelihood that events were treatment-related (scale = 0-4). The cumulative incidence of decompensation/events was 6.4% for the total cohort. Among 499 previously stable patients, the incidence of decompensation/events was 4.5%; the mortality rate was 0.6%. Sixteen of the 499 experienced one or more serious complications considered to be at least potentially treatment-related, and the sustained virological response rate was 7/16 (44%). Two cases, both on sofosbuvir/simeprevir (without interferon or ribavirin), had complications consistent with autoimmune events (score 3, 'likely treatment-related'), and one experienced a flare of autoimmune hepatitis. Compared to controls, cases had higher baseline median model for end-stage liver disease scores (14 vs 8, P < 0.01). Decompensation/events was independently associated with lower baseline albumin (OR = 0.12/g/dL, P = 0.01) and higher total bilirubin (OR = 4.31/mg/dL, P = 0.01). Reduced hepatic function at baseline increased the risk of liver decompensation/events. PMID:26989855

  5. The Biological Effects of Bilirubin Photoisomers.

    PubMed

    Jasprova, Jana; Dal Ben, Matteo; Vianello, Eleonora; Goncharova, Iryna; Urbanova, Marie; Vyroubalova, Karolina; Gazzin, Silvia; Tiribelli, Claudio; Sticha, Martin; Cerna, Marcela; Vitek, Libor

    2016-01-01

    Although phototherapy was introduced as early as 1950's, the potential biological effects of bilirubin photoisomers (PI) generated during phototherapy remain unclear. The aim of our study was to isolate bilirubin PI in their pure forms and to assess their biological effects in vitro. The three major bilirubin PI (ZE- and EZ-bilirubin and Z-lumirubin) were prepared by photo-irradiation of unconjugated bilirubin. The individual photoproducts were chromatographically separated (TLC, HPLC), and their identities verified by mass spectrometry. The role of Z-lumirubin (the principle bilirubin PI) on the dissociation of bilirubin from albumin was tested by several methods: peroxidase, fluorescence quenching, and circular dichroism. The biological effects of major bilirubin PI (cell viability, expression of selected genes, cell cycle progression) were tested on the SH-SY5Y human neuroblastoma cell line. Lumirubin was found to have a binding site on human serum albumin, in the subdomain IB (or at a close distance to it); and thus, different from that of bilirubin. Its binding constant to albumin was much lower when compared with bilirubin, and lumirubin did not affect the level of unbound bilirubin (Bf). Compared to unconjugated bilirubin, bilirubin PI did not have any effect on either SH-SY5Y cell viability, the expression of genes involved in bilirubin metabolism or cell cycle progression, nor in modulation of the cell cycle phase. The principle bilirubin PI do not interfere with bilirubin albumin binding, and do not exert any toxic effect on human neuroblastoma cells. PMID:26829016

  6. Bilirubin - urine

    MedlinePlus

    ... or gallbladder Considerations Bilirubin can break down in light. That is why babies with jaundice are sometimes placed under blue fluorescent lamps. Alternative Names Conjugated bilirubin - urine; Direct bilirubin - ...

  7. Use of 125I- and 51Cr-Labeled Albumin for the Measurement of Gastrointestinal and Total Albumin Catabolism*

    PubMed Central

    Kerr, Robert M.; Bois, John J. Du; Holt, Peter R.

    1967-01-01

    A method for the simultaneous measurement of gastrointestinal protein loss and total albumin turnover entailing the use of a combination of 125iodine- and 51chromium-labeled albumin is described. Albumin turnover was calculated by the measurement of albumin-125I plasma decay and cumulative urinary excretion, and the results obtained agreed closely with previous studies utilizing albumin-131I. Gastrointestinal catabolism was calculated from the rate of fecal excretion of 51Cr and the specific activity of plasma albumin-51Cr, and these data were related to the calculated albumin turnover results. During the period of 6-14 days after administration, the ratio of specific activties of albumin-125I and -51Cr in plasma and in extravascular spaces or gastric and biliary secretions remained almost identical. Fecal excretion of 51Cr was also quite stable at this time. In six normal subjects gastrointestinal catabolism accounted for less than 10% of total albumin catabolism. Excessive gastrointestinal protein losses did not contribute to the low serum albumin in three patients with cirrhosis or in two adults with the nephrotic syndrome. Multiple mechanisms leading to hypoalbuminemia were demonstrated in other subjects with a variety of gastrointestinal disorders. Images PMID:5630419

  8. Body Fat Percentage Is a Major Determinant of Total Bilirubin Independently of UGT1A1*28 Polymorphism in Young Obese

    PubMed Central

    Kohlova, Michaela; Bronze-da-Rocha, Elsa; Fernandes, João; Costa, Elísio; Catarino, Cristina; Aires, Luísa; Mansilha, Helena Ferreira; Rocha-Pereira, Petronila; Quintanilha, Alexandre; Rêgo, Carla; Santos-Silva, Alice

    2014-01-01

    Objectives Bilirubin has potential antioxidant and anti-inflammatory properties. The UGT1A1*28 polymorphism (TA repeats in the promoter region) is a major determinant of bilirubin levels and recent evidence suggests that raised adiposity may also be a contributing factor. We aimed to study the interaction between UGT1A1 polymorphism, hematological and anthropometric variables with total bilirubin levels in young individuals. Methods 350 obese (mean age of 11.6 years; 52% females) and 79 controls (mean age of 10.5 years; 59% females) were included. Total bilirubin and C-reactive protein (CRP) plasma levels, hemogram, anthropometric data and UGT1A1 polymorphism were determined. In a subgroup of 74 obese and 40 controls body composition was analyzed by dual-energy X-ray absorptiometry. Results The UGT1A1 genotype frequencies were 49.9%, 42.7% and 7.5% for 6/6, 6/7 and 7/7 genotypes, respectively. Patients with 7/7 genotype presented the highest total bilirubin levels, followed by 6/7 and 6/6 genotypes. Compared to controls, obese patients presented higher erythrocyte count, hematocrit, hemoglobin and CRP levels, but no differences in bilirubin or in UGT1A1 genotype distribution. Body fat percentage was inversely correlated with bilirubin in obese patients but not in controls. This inverse association was observed either in 6/7 or 6/6 genotype obese patients. UGT1A1 polymorphism and body fat percentage were the main factors affecting bilirubin levels within obese patients (linear regression analysis). Conclusion In obese children and adolescents, body fat composition and UGT1A1 polymorphism are independent determinants of total bilirubin levels. Obese individuals with 6/6 UGT1A1 genotype and higher body fat mass may benefit from a closer clinical follow-up. PMID:24901842

  9. Bilirubin Test

    MedlinePlus

    ... test in conjunction with other laboratory tests ( alkaline phosphatase , aspartate aminotransferase , alanine aminotransferase ) when someone shows signs ... Gilbert syndrome, due to low levels of the enzyme that produces conjugated bilirubin If conjugated (direct) bilirubin ...

  10. Serum Total Bilirubin Levels Provide Additive Risk Information over the Framingham Risk Score for Identifying Asymptomatic Diabetic Patients at Higher Risk for Coronary Artery Stenosis

    PubMed Central

    Leem, Jaechan; Koh, Eun Hee; Jang, Jung Eun; Woo, Chang-Yun; Oh, Jin Sun; Lee, Min Jung; Kang, Joon-Won; Lim, Tae-Hwan; Jung, Chang Hee; Lee, Woo Je; Park, Joong-Yeol

    2015-01-01

    Background The diagnosis of coronary artery disease (CAD) is often delayed in patients with type 2 diabetes. Serum total bilirubin levels are inversely associated with CAD. However, no studies have examined whether this can be used as a biochemical marker for identifying asymptomatic diabetic patients at higher risk for having obstructive CAD. Methods We performed a cross-sectional study of 460 consecutive asymptomatic patients with type 2 diabetes. All patients underwent coronary computed tomographic angiography, and their serum total bilirubin levels were measured. Obstructive CAD was defined as ≥50% diameter stenosis in at least one coronary artery. Results Serum total bilirubin tertiles showed an inverse association with the prevalence of obstructive CAD. In multivariate logistic regression analysis, the odds ratio for the highest versus the lowest tertile of total bilirubin was 0.227 (95% confidence interval [CI], 0.130 to 0.398), and an increment of 1 µmol/L in serum total bilirubin level was associated with a 14.6% decrease in obstructive CAD after adjustment for confounding variables. Receiver operating characteristic curve analysis showed that the area under the curve for the Framingham Risk Score (FRS) plus serum total bilirubin level was 0.712 (95% CI, 0.668 to 0.753), which is significantly greater than that of the FRS alone (P=0.0028). Conclusion Serum total bilirubin level is inversely associated with obstructive CAD and provides additive risk information over the FRS. Serum total bilirubin may be helpful for identifying asymptomatic patients with type 2 diabetes who are at higher risk for obstructive CAD. PMID:26566499

  11. The Biological Effects of Bilirubin Photoisomers

    PubMed Central

    Jasprova, Jana; Dal Ben, Matteo; Vianello, Eleonora; Goncharova, Iryna; Urbanova, Marie; Vyroubalova, Karolina; Gazzin, Silvia; Tiribelli, Claudio; Sticha, Martin; Cerna, Marcela; Vitek, Libor

    2016-01-01

    Although phototherapy was introduced as early as 1950’s, the potential biological effects of bilirubin photoisomers (PI) generated during phototherapy remain unclear. The aim of our study was to isolate bilirubin PI in their pure forms and to assess their biological effects in vitro. The three major bilirubin PI (ZE- and EZ-bilirubin and Z-lumirubin) were prepared by photo-irradiation of unconjugated bilirubin. The individual photoproducts were chromatographically separated (TLC, HPLC), and their identities verified by mass spectrometry. The role of Z-lumirubin (the principle bilirubin PI) on the dissociation of bilirubin from albumin was tested by several methods: peroxidase, fluorescence quenching, and circular dichroism. The biological effects of major bilirubin PI (cell viability, expression of selected genes, cell cycle progression) were tested on the SH-SY5Y human neuroblastoma cell line. Lumirubin was found to have a binding site on human serum albumin, in the subdomain IB (or at a close distance to it); and thus, different from that of bilirubin. Its binding constant to albumin was much lower when compared with bilirubin, and lumirubin did not affect the level of unbound bilirubin (Bf). Compared to unconjugated bilirubin, bilirubin PI did not have any effect on either SH-SY5Y cell viability, the expression of genes involved in bilirubin metabolism or cell cycle progression, nor in modulation of the cell cycle phase. The principle bilirubin PI do not interfere with bilirubin albumin binding, and do not exert any toxic effect on human neuroblastoma cells. PMID:26829016

  12. Bilirubin Neurotoxicity in Preterm Infants: Risk and Prevention

    PubMed Central

    Bhutani, Vinod K.; Wong, Ronald J.

    2013-01-01

    Hemolytic conditions in preterm neonates, including Rhesus (Rh) disease, can lead to mortality and long-term impairments due to bilirubin neurotoxicity. Universal access to Rh immunoprophylaxis, coordinated perinatal-neonatal care, and effective phototherapy has virtually eliminated the risk of kernicterus in many countries. In the absence of jaundice due to isoimmunization and without access to phototherapy or exchange transfusion (in 1955), kernicterus was reported at 10.1%, 5.5%, and 1.2% in babies <30, 31-32, and 33-34 wks gestational age, respectively. Phototherapy initiated at 24±12 hr effectively prevented hyperbilirubinemia in infants <2,000 g even in the presence of hemolysis. This approach (in 1985) reduced exchange transfusions from 23.9% to 4.8%. Now with 3 decades of experience in implementing effective phototherapy, the need for exchange transfusions has virtually been eliminated. However, bilirubin neurotoxicity continues to be associated with prematurity alone. The ability to better predict this risk, other than birthweight and gestation, has been elusive. Objective tests such as total bilirubin, unbound or free bilirubin, albumin levels, and albumin-bilirubin binding, together with observations of concurrent hemolysis, sepsis, and rapid rate of bilirubin rise have been considered, but their individual or combined predictive utility has yet to be refined. The disruptive effects of immaturity, concurrent neonatal disease, cholestasis, use of total parenteral nutrition or drugs that alter bilirubin-binding abilities augment the clinical risk of neurotoxicity. Current management options rely on the “fine-tuning” of each infant's exposure to beneficial antioxidants and avoidance of silent neurotoxic properties of bilirubin navigated within the safe spectrum of operational thresholds demarcated by experts. PMID:24049745

  13. High Total Bilirubin as a Protective Factor for Diabetes Mellitus: An Analysis of NHANES Data From 1999 - 2006

    PubMed Central

    Cheriyath, Pramil; Gorrepati, Venkata Subhash; Peters, Ian; Nookala, Vinod; Murphy, Megan E; Srouji, Nadine; Fischman, Daniel

    2010-01-01

    Background Diabetes Mellitus (DM) is a rampantly growing epidemic in the United States, affecting nearly 10% of the adult population. Studies have shown that higher levels of Total Bilirubin (TBili) convey a protective effect with regard to cardiovascular risk. In this study, we will examine the relationship between TBili level and prevalence of DM to discern whether a similar relationship exists. Methods The National Health and Nutrition Examination Survey (NHANES) is a comprehensive survey performed regularly to evaluate the overall health and nutrition status of the United States population. For the purpose of this study, we combined NHANES data collected between 1999 and 2006. Totally 15,876 eligible participants were selected after excluding all patients younger than twenty years, those with a history of abnormal liver function tests, or those who disclosed a history of liver disease. The data collected on these individuals was adjusted for demographic characteristics, as well as risk factors for DM, and was analyzed via multivariate logistic regression, using SAS proc survey methodology. Results After age adjustment, increased TBili was associated with 26% reduction in diabetes risk (OR 0.74, 95% CI 0.64 - 0.88). Multivariate analysis, adjusting for all diabetes risk factors assessed, confirmed this association (OR 0.80, 95% CI 0.67 - 0.95). Conclusions Our results show that a higher level of serum TBili is associated with odds of having a lower incidence of DM. This finding supports the hypothesis that the antioxidant nature of TBili, demonstrating a protective effect with regard to the risk of stroke, atherosclerosis, and vasculitis in prior research, also extends to DM risk. Furthermore, research has shown that higher levels of TBili increase glucose mobilization into the cells, leading to more efficient, biologic glucose utilization. There is no doubt that the beneficial effect of TBili is multifactorial; thus further investigation is warranted. Keywords

  14. Higher serum total bilirubin concentration is associated with lower risk of renal insufficiency in an adult population

    PubMed Central

    Lee, Ang-Tse; Wang, Ya-Yu; Lin, Shih-Yi; Liang, Jiin-Tsae; Sheu, Wayne Huey-Herng; Song, Yuh-Min; Chang, Wen-Dau

    2015-01-01

    Background: Chronic inflammation is proposed to play a central role in the pathogenesis of chronic kidney disease (CKD), and serum bilirubin has antioxidant and anti-inflammatory effects. We investigated the association between serum total bilirubin (Tb) concentration and renal function in an adult population. Methods: We conducted a cross-sectional study and collected anthropometric measurements, fasting blood tests, lifestyle habits and medical history of 3876 subjects attending a health examination. Renal insufficiency was defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 calculated by using the CKD-EPI equation. Results: Serum Tb concentrations were higher in subjects without renal insufficiency than in those with renal insufficiency. Multivariable linear regression analysis showed that Tb concentration was positively associated with eGFR after adjusting for important CKD risk factors (P=0.04). Multivariable logistic regression analysis also revealed that higher Tb concentration (each increment of 1.71 μmol/L) (0.1 mg/dL) was associated with a reduced risk of renal insufficiency: odds ratios were 0.94 (P=0.005) for men and 0.90 (P=0.015) for women, respectively. When subjects were divided into quartiles of serum Tb, multivariable-adjusted odds ratios for renal insufficiency comparing the fourth to the first Tb quartile were 0.49 (P=0.001) for men and 0.35 (P=0.003) for women. A stepwise exclusion of subjects, first those with possible liver disease and second, those with CKD stage 4 and 5, showed consistent results. Conclusion: Higher serum Tb concentration was associated with lower risk of renal insufficiency, regardless of other conventional CKD risk factors. PMID:26770557

  15. Bilirubin - blood

    MedlinePlus

    ... bilirubin is not processed normally by the liver ( Gilbert disease ) The following problems with gallbladder or bile ... Choledocholithiasis Cirrhosis Crigler-Najjar syndrome Dubin-Johnson syndrome Gilbert disease Glucose-6-phosphate dehydrogenase deficiency Hemoglobin Hemolytic ...

  16. Total oxidant status, total antioxidant capacity and ischemia modified albumin levels in children with celiac disease.

    PubMed

    Sayar, Ersin; Özdem, Sebahat; Uzun, Gülbahar; İşlek, Ali; Yılmaz, Aygen; Artan, Reha

    2015-01-01

    In our study, we aimed to investigate ischemia modified albumin (IMA) as an oxidative stress marker, as well as other oxidant and antioxidant markers that have not been evaluated in children with celiac disease. A total of 37 pediatric patients who were diagnosed with celiac disease (CD) and 29 healthy children were enrolled in this prospective study. We evaluated the IMA, total oxidant status, total antioxidant capacity, sulfhydryl, and advanced oxidation protein products in all of the subjects. We also compared the levels at the time of the diagnosis, and following a gluten-free diet (GFD) in the children with CD. While the IMA and the other oxidant marker levels were significantly higher in the patient group compared to the control group, the antioxidant marker levels were found to be significantly lower in the patient group, compared to the control group. We also determined that the tissue transglutaminase IgA showed a highly positive correlation, and that the IMA showed a moderately positive correlation with the Marsh-Oberhuber histopathological stage. Additionally, the IMA and other oxidant marker levels were significantly lower, while the antioxidant marker levels were significantly higher after the GFD, compared to the pre-diet period. We detected that oxidative stress played a role in the pathogenesis of CD, and that this could be evaluated using oxidative stress markers, which would regress after the GFD. We also detected that IMA is a marker that shows a correlation with the histopathological stage, and may be used in the diagnosis. PMID:27411418

  17. Continuous versus intermittent exercise effects on urinary excretion of albumin and total protein.

    PubMed

    Montelpare, W J; Klentrou, P; Thoden, J

    2002-09-01

    Several studies have reported post-exercise increases of urinary concentrations of plasma proteins. However, under normal conditions, through mechanisms of size and electrical charge selection, the kidney restricts the clearance of molecules as large as albumin. Post-exercise increases in albuminuria occur following the physiological stress of intense exercise, most likely as a result of the exercise induced blood acidity changes which lead to a change in the arrangement of the albumin molecule, and subsequently the filtration characteristics of the glomerular capillary wall. The purpose of the present study was therefore to determine the extent to which different types of exercise could induce a transient condition of post-exercise increases in the urinary output of total protein and albumin. All 14 males, who agreed to participate in the study, performed a continuous and an intermittent cycling protocol on a stationary bicycle ergometer. The results showed that: a) intermittent exercise had a greater influence than continuous exercise on the total output of urine albumin, and of urine total protein; b) concentrations of blood pH and blood lactate, were associated with changes in the clearance of urine albumin and urine total protein. Post-exercise proteinuria response seems to be transient and therefore renal trauma is not suspected at the early stages of observation. Furthermore, these results indicate that the kidney undergoes distinct physiological adjustments during exercise, and that these adjustments are relative to the intensity of the exercise stress. PMID:12413038

  18. Study of the effect of total serum protein and albumin concentrations on canine fructosamine concentration.

    PubMed Central

    Loste, A; Marca, M C

    1999-01-01

    The relationship among serum fructosamine concentration and total serum protein and albumin concentrations were evaluated in healthy and sick dogs (diabetics and dogs with insulinoma were not included). Fructosamine was determined using a commercial colorimetric nitroblue tetrazolium method applied to the Technicon RA-500 (Bayer). Serum fructosamine concentration was not correlated to total protein in normoproteinemic (r = 0.03) and hyperproteinemic dogs (r = 0.29), but there was a high correlation (r = 0.73) in hypoproteinemic dogs. Similar comparison between serum fructosamine and albumin concentrations showed middle correlation (r = 0.49) in normoalbuminemic dogs and high degree of correlation (r = 0.67) in hypoalbuminemic dogs. These results showed the importance of recognizing serum glucose concentration as well as total serum protein and albumin concentrations in the assay of canine serum fructosamine concentration. PMID:10369572

  19. Bilirubin chemistry and metabolism; harmful and protective aspects.

    PubMed

    Vítek, Libor; Ostrow, J Donald

    2009-01-01

    Unconjugated bilirubin (UCB), the principal mammalian bile pigment, is the end product of heme catabolism. Both belong to the superfamily of tetrapyrrolic compounds that serve multiple biological functions in animals and plants. Its six internal hydrogen bonds give UCB a unique structure responsible for its physico-chemical properties and biological effects. Like many weakly-polar, poorly-soluble compounds, UCB is transported in blood tightly bound to albumin, with less than 0.01% of total bilirubin circulating in an unbound form (free bilirubin, Bf). This fraction governs the diffusion of UCB into tissues, and therefore Bf is responsible for both its beneficial and toxic effects on cells. Although, UCB was long thought to be a non-functional waste product, recent studies have shown that the antioxidant effects of mildly elevated serum bilirubin levels, as well as activation of heme oxygenase, may protect against diseases associated with oxidative stress, such as atherosclerosis. By contrast, markedly elevated serum UCB levels may cause severe neurological damage, especially in neonates. The regulation of cellular UCB content, by its conjugation, oxidation, and export, are, therefore of paramount importance to cellular health. PMID:19754364

  20. Relation of plasma calcium to total protein and albumin in African grey (Psittacus erithacus) and Amazon (Amazona spp.) parrots.

    PubMed

    Lumeij, J T

    1990-10-01

    A significant correlation was found between total calcium and albumin concentration in the plasma of 70 African grey parrots (r=0.37; P<0.05). A correlation formula for plasma calcium concentration in the African grey parrot was derived on the basis of the concentration of albumin: Adjusted Ca (mmol/1) = Ca (mmol/1) - 0.015 Albumin (g/1) + 0.4. About 14% of the variability in calcium was attributable to the change in the concentration of plasma albumin concentration (R2=0.137). The correlation between calcium and total protein in African greys and between calcium and albumin and calcium and total protein in Amazons was not significant. PMID:18679980

  1. TOTAL LYMPHOCYTE COUNT AND SERUM ALBUMIN AS PREDICTORS OF NUTRITIONAL RISK IN SURGICAL PATIENTS

    PubMed Central

    ROCHA, Naruna Pereira; FORTES, Renata Costa

    2015-01-01

    Background: Early detection of changes in nutritional status is important for a better approach to the surgical patient. There are several nutritional measures in clinical practice, but there is not a complete method for determining the nutritional status, so, health professionals should only choose the best method to use. Aim: To evaluate the total lymphocyte count and albumin as predictors of identification of nutritional risk in surgical patients. Methods: Prospective longitudinal study was conducted with 69 patients undergoing surgery of the gastrointestinal tract. The assessment of nutritional status was evaluated by objective methods (anthropometry and biochemical tests) and subjective methods (subjective global assessment). Results: All parameters used in the nutritional assessment detected a high prevalence of malnutrition, with the exception of BMI which detected only 7.2% (n=5). The albumin (p=0.01), the total lymphocytes count (p=0.02), the percentage of adequacy of skinfolds (p<0.002) and the subjective global assessment (p<0.001) proved to be useful as predictors of risk of postoperative complications, since the smaller the values of albumin and lymphocyte count and higher the score the subjective global assessment were higher risks of surgical complications. Conclusions: A high prevalence of malnutrition was found, except for BMI. The use of albumin and total lymphocyte count were good predictor for the risk of postoperative complications and when used with other methods of assessing the nutritional status, such as the subjective global assessment and the percentage of adequacy of skinfolds, can be useful for identification of nutritional risk and postoperative complications. PMID:26537145

  2. Simple and sensitive method for the quantification of total bilirubin in human serum using 3-methyl-2-benzothiazolinone hydrazone hydrochloride as a chromogenic probe

    NASA Astrophysics Data System (ADS)

    Nagaraja, Padmarajaiah; Avinash, Krishnegowda; Shivakumar, Anantharaman; Dinesh, Rangappa; Shrestha, Ashwinee Kumar

    2010-11-01

    We here describe a new spectrophotometric method for measuring total bilirubin in serum. The method is based on the cleavage of bilirubin giving formaldehyde which further reacts with diazotized 3-methyl-2-benzothiazolinone hydrazone hydrochloride giving blue colored solution with maximum absorbance at 630 nm. Sensitivity of the developed method was compared with Jendrassik-Grof assay procedure and its applicability has been tested with human serum samples. Good correlation was attained between both methods giving slope of 0.994, intercept 0.015, and R2 = 0.997. Beers law obeyed in the range of 0.068-17.2 μM with good linearity, absorbance y = 0.044 Cbil + 0.003. Relative standard deviation was 0.006872, within day precision ranged 0.3-1.2% and day-to-day precision ranged 1-6%. Recovery of the method varied from 97 to 102%. The proposed method has higher sensitivity with less interference. The obtained product was extracted and was spectrally characterized for structural confirmation with FT-IR, 1H NMR.

  3. Quantitative assessment of the multiple processes responsible for bilirubin homeostasis in health and disease

    PubMed Central

    Levitt, David G; Levitt, Michael D

    2014-01-01

    Serum bilirubin measurements are commonly obtained for the evaluation of ill patients and to screen for liver disease in routine physical exams. An enormous research effort has identified the multiple mechanisms involved in the production and metabolism of conjugated (CB) and unconjugated bilirubin (UB). While the qualitative effects of these mechanisms are well understood, their expected quantitative influence on serum bilirubin homeostasis has received less attention. In this review, each of the steps involved in bilirubin production, metabolism, hepatic cell uptake, and excretion is quantitatively examined. We then attempt to predict the expected effect of normal and defective function on serum UB and CB levels in health and disease states including hemolysis, extra- and intrahepatic cholestasis, hepatocellular diseases (eg, cirrhosis, hepatitis), and various congenital defects in bilirubin conjugation and secretion (eg, Gilbert’s, Dubin–Johnson, Crigler–Najjar, Rotor syndromes). Novel aspects of this review include: 1) quantitative estimates of the free and total UB and CB in the plasma, hepatocyte, and bile; 2) detailed discussion of the important implications of the recently recognized role of the hepatic OATP transporters in the maintenance of CB homeostasis; 3) discussion of the differences between the standard diazo assay versus chromatographic measurement of CB and UB; 4) pharmacokinetic implications of the extremely high-affinity albumin binding of UB; 5) role of the enterohepatic circulation in physiologic jaundice of newborn and fasting hyperbilirubinemia; and 6) insights concerning the clinical interpretation of bilirubin measurements. PMID:25214800

  4. Blood Test: Bilirubin

    MedlinePlus

    ... two forms in the body: indirect (unconjugated) and direct (conjugated). Indirect bilirubin, which doesn't dissolve in ... liver to be changed into the soluble form, direct bilirubin. Why It's Done Healthy newborns — especially those ...

  5. Efficacy of Human Adipose Tissue-Derived Stem Cells on Neonatal Bilirubin Encephalopathy in Rats.

    PubMed

    Amini, Naser; Vousooghi, Nasim; Hadjighassem, Mahmoudreza; Bakhtiyari, Mehrdad; Mousavi, Neda; Safakheil, Hosein; Jafari, Leila; Sarveazad, Arash; Yari, Abazar; Ramezani, Sara; Faghihi, Faezeh; Joghataei, Mohammad Taghi

    2016-05-01

    Kernicterus is a neurological syndrome associated with indirect bilirubin accumulation and damages to the basal ganglia, cerebellum and brain stem nuclei particularly the cochlear nucleus. To mimic haemolysis in a rat model such that it was similar to what is observed in a preterm human, we injected phenylhydrazine in 7-day-old rats to induce haemolysis and then infused sulfisoxazole into the same rats at day 9 to block bilirubin binding sites in the albumin. We have investigated the effectiveness of human adiposity-derived stem cells as a therapeutic paradigm for perinatal neuronal repair in a kernicterus animal model. The level of total bilirubin, indirect bilirubin, brain bilirubin and brain iron was significantly increased in the modelling group. There was a significant decreased in all severity levels of the auditory brainstem response test in the two modelling group. Akinesia, bradykinesia and slip were significantly declined in the experience group. Apoptosis in basal ganglia and cerebellum were significantly decreased in the stem cell-treated group in comparison to the vehicle group. All severity levels of the auditory brainstem response tests were significantly decreased in 2-month-old rats. Transplantation results in the substantial alleviation of walking impairment, apoptosis and auditory dysfunction. This study provides important information for the development of therapeutic strategies using human adiposity-derived stem cells in prenatal brain damage to reduce potential sensori motor deficit. PMID:26818600

  6. Serum Total Bilirubin, not Cholelithiasis, is Influenced by UGT1A1 Polymorphism, Alpha Thalassemia and βs Haplotype: First Report on Comparison between Arab-Indian and African βs Genes

    PubMed Central

    Alkindi, Said Y.; Pathare, Anil; Al Zadjali, Shoaib; Panjwani, Vinodhkumar; Wasim, Fauzia; Khan, Hammad; Chopra, Pradeep; Krishnamoorthy, Rajagopal; Alkindi, Salam

    2015-01-01

    Background We explored the potential relationship between steady state serum bilirubin levels and the incidence of cholelithiasis in the context of UGT1A1 gene A(TA)nTAA promoter polymorphism in Omani sickle cell anemia (SCA) patients, homozygotes for African (Benin and Bantu) and Arab-Indian βS haplotypes, but sharing the same microgeographical environment and comparable life style factors. Methods 136 SCA patients were retrospectively studied in whom imaging data including abdominal CT scan, MRI or Ultrasonography were routinely available. Available data on the mean steady state hematological/biochemical parameters (n=136), βs haplotypes(n=136), α globin gene status (n=105) and UGT1A1 genotypes (n=133) were reviewed from the respective medical records. Results The mean serum total bilirubin level was significantly higher in the homozygous UGT1A1(AT)7 group as compared to UGT1A1(AT)6 group. Thus, not cholelithiasis but total serum bilirubin was influenced by UGT1A1 polymorphism in this SCA cohort. Conclusion As observed in other population groups, the UGT1A1 (AT)7 homozygosity was significantly associated with raised serum total bilirubin level, but the prevalence of gallstones in the Omani SCA patients was not associated with α thalassaemia, UGT1A1 polymorphism, or βs haplotypes. PMID:26543529

  7. Early postoperative albumin level following total knee arthroplasty is associated with acute kidney injury

    PubMed Central

    Kim, Ha-Jung; Koh, Won-Uk; Kim, Sae-Gyeol; Park, Hyeok-Seong; Song, Jun-Gol; Ro, Young-Jin; Yang, Hong-Seuk

    2016-01-01

    Abstract Hypoalbuminemia has been reported to be an independent risk factor for acute kidney injury (AKI). However, little is known about the relationship between the albumin level and the incidence of AKI in patients undergoing total knee arthroplasty (TKA). The aim of our study was to assess incidence and risk factors for AKI and to evaluate the relationship between albumin level and AKI following TKA. The study included a retrospective review of medical records of 1309 consecutive patients who underwent TKA between January 2008 and December 2014. The patients were divided into 2 groups according to the lowest serum albumin level within 2 postoperative days (POD2_alb level < 3.0 g/dL vs ≥3.0 g/dL). Multivariate logistic regression analysis was used to assess risk factors for AKI. A comparison of incidence of AKI, hospital stay, and overall mortality in the 2 groups was performed using propensity score analysis. Of 1309 patients, 57 (4.4%) developed AKI based on Kidney Disease Improving Global Outcomes criteria. Factors associated with AKI included age (odds ratio [OR] 1.05; 95% confidence interval [CI] 1.01–1.09; P = 0.030), diabetes (OR 3.12; 95% CI 1.65–5.89; P < 0.001), uric acid (OR 1.51; 95% CI 1.26–1.82; P < 0.001), beta blocker use (OR 2.65; 95% CI 1.48–4.73; P = 0.001), diuretics (OR 16.42; 95% CI 3.08–87.68; P = 0.001), and POD2_alb level < 3.0 g/dL (OR 1.92; 95% CI 1.09–3.37; P = 0.023). After propensity score analysis, POD2_alb level<3.0 g/dL was associated with AKI occurrence (OR 1.82; 95% CI 1.03–3.24, P = 0.041) and longer hospital stay (P = 0.001). In this study, we demonstrated that POD2_alb level<3.0 g/dL was an independent risk factor for AKI and lengthened hospital stay in patients undergoing TKA. PMID:27495094

  8. [Cytoprotective effects of bilirubin].

    PubMed

    Vítek, L

    2005-01-01

    Bilirubin, a major product of heme catabolism, belongs to compounds with pleiotropic biologic effects. For a long time bilirubin was considered as a metabolite dangerous for human health, neonatologists know well serious clinical complication of neonatal jaundice called bilirubin encephalopathy. Nevertheless, recent data has demonstrated that bilirubin exhibits potent antioxidant and even anti-inflammatory effects with substantial clinical impacts. The aim of the present study was to summarize present knowledge in this rapidly evolving field and suggest further possible clinical consequences. PMID:15981989

  9. The Association between Diabetic Retinopathy and Levels of Ischemia-Modified Albumin, Total Thiol, Total Antioxidant Capacity, and Total Oxidative Stress in Serum and Aqueous Humor

    PubMed Central

    Kirboga, Kadir; Ozec, Ayse V.; Kosker, Mustafa; Dursun, Ayhan; Toker, Mustafa I.; Aydin, Huseyin; Erdogan, Haydar; Topalkara, Aysen; Arici, Mustafa K.

    2014-01-01

    Purpose. To investigate the oxidant and antioxidant status of patients with type 2 diabetes mellitus and nonproliferative diabetic retinopathy (DRP). Methods. Forty-four patients who had cataract surgery were enrolled in the study. We included 22 patients with DRP in one group and 22 patients in the control group. Samples of aqueous humor and serum were taken from all patients. Serum and aqueous ischemia-modified albumin (IMA), total thiol, total antioxidant capacity (TAC), and total oxidative stress (TOS) levels were compared in two groups. Results. Median serum IMA levels were 44.80 absorbance units in the DRP group and 40.15 absorbance units in the control group (P = 0.031). Median serum total thiol levels in the DRP group were significantly less than those in the control group (3051.13 and 3910.12, resp., P = 0.004). Mean TOS levels in the serum were 2.93 ± 0.19 in the DRP group and 2.61 ± 0.26 in the control group (P = 0.039). The differences in mean total thiol, TAC, and TOS levels in the aqueous humor and mean TAC levels in the serum were not statistically significant. Conclusion. IMA, total thiol, and TOS levels in the serum might be useful markers in monitoring the risk of DRP development. PMID:25580282

  10. [Does bilirubin interfere with capillary electrophoresis of serum proteins?].

    PubMed

    Hellara, Ilhem; Fekih, Ons; Triki, Sonia; Elmay, Ahlem; Neffati, Fadoua; Najjar, Mohamed Fadhel

    2014-01-01

    Capillary electrophoresis of serum proteins is a fast, reliable and simple technique, but many interference exist. The objective of our work is to study the interference of bilirubin on this technique; 70 icteric sera were analysed on Capillarys ™ (Sebia). A second electrophoresis was performed on 40 samples after bilirubin photodegradation. The bilirubin and serum proteins were determinated respectively by Jendrassik and Grof and biuret methods on Konélab 20i ™ (Thermo Electron Corporation). We found abnormal spreading of the albumin fraction of the anode side wich constitute sometimes an isolated fraction in the traditional area of pre-albumin migration. This fraction varies from 2.0 ± 2.0% (0.0 to 7.3%) or 0.98 ± 1.53 g/L (0 to 5.3 g/L) and it seems to be related to the direct bilirubin since, following overloading sera with a solution of bilirubin, no further fraction was recovered. An average decrease of bilirubin after photodegradation of 58 ± 17% (26-89%) is followed by a decrease in the same order 64 ± 38% (10-100%) of the additional fraction. Acetate cellulose electrophoresis of the same samples showed no variation. The high bilirubin levels seem modify slightly the electrophoretic profile. However the impact of the interference on the interpretation of electrophoretic trace is negligible. PMID:24492101

  11. Effect of processing methods on colouration of human serum albumin preparations.

    PubMed

    McCann, Karl B; Vucica, Yvonne; Famulari, Sandy; Bertolini, Joseph

    2009-01-01

    Human serum albumin is a well tolerated therapeutic for the treatment of hypovolemia. Despite all commercial human albumin preparations being derived from plasma, these products can have a highly variable colour. Albumin samples derived from ethanol precipitation and chromatographic fractionation procedures were evaluated for bilirubin and biliverdin levels and by spectrophotometry. It was shown that albumin derived from a chromatographic process, which had a bilirubin:albumin ratio similar to that observed in plasma, had a vibrant yellow appearance. The albumin derived from ethanol precipitation had undetectable levels of bilirubin, and the amber colour of this product was attributed mainly to residual haem. The presence of bilirubin during pasteurisation led to oxidation to biliverdin, with a resultant colour change from yellow to yellow/green. Given that the antioxidant properties of bilirubin are well established, it is possible that bilirubin helps protect albumin from oxidation during the pasteurisation step. PMID:18948018

  12. Enzymic oxidation of unconjugated bilirubin by rat liver.

    PubMed Central

    Cardenas-Vazquez, R; Yokosuka, O; Billing, B H

    1986-01-01

    The presence of the enzyme bilirubin oxidase, which degrades bilirubin in vitro, was demonstrated in the liver. Subcellular-fractionation experiments indicate that bilirubin oxidase is located in both the inner and outer membranes of the mitochondria. The mean rate of the reaction is 1.57 +/- 0.38 (S.D.) nmol of bilirubin degraded/min per mg of mitochondrial protein (munits/mg of protein). With respect to the overall breakdown of bilirubin, the enzyme has a Km' of 136 microM-bilirubin and a Vmax.' of 9.13 munits/mg of protein. Its activity is influenced by the ionic strength of the media and is inhibited by KCN, thiol reagents, NADH and albumin. The enzyme is aerobic, and between 1 and 1.5 mol of O2 are consumed per mol of bilirubin degraded. The products of the reaction include propentdyopents. The hepatic bilirubin oxidase activity of the jaundiced Gunn-rat liver is not significantly different from that of the Sprague-Dawley rat, and it is not induced by beta-naphthoflavone. PMID:3790083

  13. Inherited Disorders of Bilirubin Clearance

    PubMed Central

    Memon, Naureen; Weinberger, Barry I; Hegyi, Thomas; Aleksunes, Lauren M

    2016-01-01

    Inherited disorders of hyperbilirubinemia may be caused by increased bilirubin production or decreased bilirubin clearance. Reduced hepatic bilirubin clearance can be due to defective 1) unconjugated bilirubin uptake and intrahepatic storage, 2) conjugation of glucuronic acid to bilirubin (e.g. Gilbert syndrome, Crigler-Najjar syndrome, Lucey-Driscoll syndrome, breast milk jaundice), 3) bilirubin excretion into bile (Dubin-Johnson syndrome), or 4) conjugated bilirubin re-uptake (Rotor syndrome). In this review, the molecular mechanisms and clinical manifestations of these conditions are described, as well as current approaches to diagnosis and therapy. PMID:26595536

  14. Mechanisms of bilirubin toxicity: clinical implications.

    PubMed

    Hansen, Thor Willy Ruud

    2002-12-01

    The basic mechanism of kernicterus and bilirubin encephalopathy has not been unequivocally determined. Much knowledge has been gained about phenomena that contribute to bilirubin neurotoxicity, and this knowledge has implications for clinical practice. Conditions that impact on blood-brain barrier function, increase brain blood flow, or impact on bilirubin metabolism, including its transport in serum, should be avoided, if possible. Such conditions include drugs and drug stabilizers that compete with bilirubin binding to albumin, or that inhibit P-glycoprotein in the blood-brain barrier, prematurity/immaturity, and clinically significant illness in the infant that involves hemolysis, respiratory and metabolic acidosis, infection, asphyxia, hypoxia and (perhaps) hyperoxia, and hyperosmolality. If these conditions are not avoidable then there should be a more aggressive approach to the treatment of hyperbilirubinemia. The limits of tolerance for hyperbilirubinemia varies among neonates and there are no tools to determine with certainty when a particular infant is approaching the danger zone. Neurological symptoms in a jaundiced infant require extreme vigilance, and, in most cases, immediate intervention. PMID:12516745

  15. Optical transcutaneous bilirubin detector

    DOEpatents

    Kronberg, James W.

    1993-01-01

    A transcutaneous bilirubin detector comprising a source of light having spectral components absorbable and not absorbable by bilirubin, a handle assembly, electronic circuitry and a fiber optic bundle connecting the assembly to the light source and circuitry. Inside the assembly is a prism that receives the light from one end of the fiber optic bundle and directs it onto the skin and directs the reflected light back into the bundle. The other end of the bundle is trifucated, with one end going to the light source and the other two ends going to circuitry that determines how much light of each kind has been reflected. A relatively greater amount absorbed by the skin from the portion of the spectrum absorbable by bilirubin may indicate the presence of the illness. Preferably, two measurements are made, one on the kneecap and one on the forehead, and compared to determine the presence of bilirubin. To reduce the impact of light absorption by hemoglobin in the blood carried by the skin, pressure is applied with a plunger and spring in the handle assembly, the pressure limited by points of a button slidably carried in the assembly that are perceived by touch when the pressure applied is sufficient.

  16. Optical transcutaneous bilirubin detector

    DOEpatents

    Kronberg, J.W.

    1991-03-04

    This invention consists of a transcutaneous bilirubin detector comprising a source of light having spectral components absorbable and not absorbable by bilirubin, a handle assembly, electronic circuitry and a fiber optic bundle connecting the assembly to the light source and circuitry. Inside the assembly is a prism that receives the light from one end of the fiber optic bundle and directs it onto the skin and directs the reflected light back into the bundle. The other end of the bundle is trifucated, with one end going to the light source and the other two ends going to circuitry that determines how much light of each kind has been reflected. A relatively greater amount absorbed by the skin from the portion of the spectrum absorbable by bilirubin may indicate the presence of the illness. Preferably, two measurements are made, one on the kneecap and one on the forehead, and compared to determine the presence of bilirubin. To reduce the impact of light absorption by hemoglobin in the blood carried by the skin, pressure is applied with a plunger and spring in the handle assembly, the pressure limited by points of a button slidably carried in the assembly that are perceived by touch when the pressure applied is sufficient.

  17. Optical transcutaneous bilirubin detector

    DOEpatents

    Kronberg, J.W.

    1993-11-09

    A transcutaneous bilirubin detector is designed comprising a source of light having spectral components absorbable and not absorbable by bilirubin, a handle assembly, electronic circuitry and a fiber optic bundle connecting the assembly to the light source and circuitry. Inside the assembly is a prism that receives the light from one end of the fiber optic bundle and directs it onto the skin and directs the reflected light back into the bundle. The other end of the bundle is trifucated, with one end going to the light source and the other two ends going to circuitry that determines how much light of each kind has been reflected. A relatively greater amount absorbed by the skin from the portion of the spectrum absorbable by bilirubin may indicate the presence of the illness. Preferably, two measurements are made, one on the kneecap and one on the forehead, and compared to determine the presence of bilirubin. To reduce the impact of light absorption by hemoglobin in the blood carried by the skin, pressure is applied with a plunger and spring in the handle assembly, the pressure limited by points of a button slidably carried in the assembly that are perceived by touch when the pressure applied is sufficient. 6 figures.

  18. Bilirubin UDP-glucuronyltransferase activity of wistar rat kidney.

    PubMed

    Foliot, A; Christoforov, B; Petite, J P; Etienne, J P; Housset, E; Dubois, M

    1975-08-01

    Wistar rat kidneys have been shown to possess a bilirubin glucuronyltransferase (BGT) activity capable of conjugating about 3/5 of the total pool of unconjugated bilirubin within 48 h of being grafted to Gunn rat hosts. Bilirubin conjugated by the kidney is taken up by the liver and excreted in the bile. Except when the bile duct is ligated, no conjugated bilirubin appears in the plasma or urine. Renal BGT activity is about 1/20th of the hepatic activity on a weight basis in Wistar rats. The Gunn rat's hyperbilirubinemia probably causes an induction of the renal enzyme since its activity doubles in 48 h. PMID:808968

  19. Albumin Dialysis for Liver Failure: A Systematic Review.

    PubMed

    Tsipotis, Evangelos; Shuja, Asim; Jaber, Bertrand L

    2015-09-01

    Albumin dialysis is the best-studied extracorporeal nonbiologic liver support system as a bridge or destination therapy for patients with liver failure awaiting liver transplantation or recovery of liver function. We performed a systematic review to examine the efficacy and safety of 3 albumin dialysis systems (molecular adsorbent recirculating system [MARS], fractionated plasma separation, adsorption and hemodialysis [Prometheus system], and single-pass albumin dialysis) in randomized trials for supportive treatment of liver failure. PubMed, Ovid, EMBASE, Cochrane's Library, and ClinicalTrials.gov were searched. Two authors independently screened citations and extracted data on patient characteristics, quality of reports, efficacy, and safety end points. Ten trials (7 of MARS and 3 of Prometheus) were identified (620 patients). By meta-analysis, albumin dialysis achieved a net decrease in serum total bilirubin level relative to standard medical therapy of 8.0 mg/dL (95% confidence interval [CI], -10.6 to -5.4) but not in serum ammonia or bile acids. Albumin dialysis achieved an improvement in hepatic encephalopathy relative to standard medical therapy with a risk ratio of 1.55 (95% CI, 1.16-2.08) but had no effect survival with a risk ratio of 0.95 (95% CI, 0.84-1.07). Because of inconsistency in the reporting of adverse events, the safety analysis was limited but did not demonstrate major safety concerns. Use of albumin dialysis as supportive treatment for liver failure is successful at removing albumin-bound molecules, such as bilirubin and at improving hepatic encephalopathy. Additional experience is required to guide its optimal use and address safety concerns. PMID:26311600

  20. Universal bilirubin screening for severe neonatal hyperbilirubinemia.

    PubMed

    Bhutani, V K; Vilms, R J; Hamerman-Johnson, L

    2010-10-01

    To reduce the incidence of severe neonatal hyperbilirubinemia affecting newborns with jaundice in the United States and to prevent kernicterus, there is a need to implement proven prevention strategies for severe neonatal hyperbilirubinemia as recommended in the 2004 American Academy of Pediatrics Guidelines for newborns >35 weeks gestational age. The purpose of universal predischarge bilirubin screening is to identify infants with bilirubin levels >75th percentile for age in hours and track those with rapid rates of bilirubin rise (>0.2 mg per 100 ml per h). Early identification has been reported to predict severe hyperbilirubinemia and allow for evidence-based targeted interventions. A systems approach is likely to reduce the preventable causes of acute bilirubin encephalopathy. To do so, highest priority should be given to (i) designating extreme hyperbilirubinemia (total serum bilirubin >427 μmol l(-1) or >25 mg per 100 ml) as a reportable condition by laboratories and health-care providers through public health mandates; (ii) implementation of Joint Commission's Sentinel Report for kernicterus; (iii) nursing outreach to communities for education of prospective parents; (iv) development of clinical pathways to monitor, evaluate and track infants with extreme hyperbilirubinemia; and (v) societal awareness. These efforts should be monitored by a state and national surveillance system in order to critically improve the timeliness and completeness of notifications and to allow evaluation and interventions at the policy and individual family level. PMID:20877410

  1. Bilirubin measurements in neonates

    NASA Astrophysics Data System (ADS)

    Newman, Gregory J.

    2000-04-01

    Infant Jaundice is a physiologic condition of elevated bilirubin in the tissue that affects nearly 60 percent of all term newborns and virtually 100 percent of premature infants. The high production of bilirubin in the newborn circulatory system and the inability of the immature liver to process and eliminate it case the condition. When the bilirubin levels rise, it starts to deposit in the baby's skin and in the brain. The deposits in the brain can cause neurologic impairment and death. The BiliCheck is a handheld, battery-powered device that measures the level of jaundice non-invasively using BioPhotonics at the point of care. The result is displayed on an LCD screen immediately, so physicians can now make treatment decision without waiting for results to return from the lab. The BiliCheck System has been marketed worldwide since April of 1998 and has received FDA clearance for use in the USA on pre-photo therapy infants in March of 1999.

  2. Quantification of total content of non-esterified fatty acids bound to human serum albumin.

    PubMed

    Pavićević, Ivan D; Jovanović, Vesna B; Takić, Marija M; Aćimović, Jelena M; Penezić, Ana Z; Mandić, Ljuba M

    2016-09-10

    Non-esterified fatty acids bound to the human serum albumin (HSA) contribute to several HSAs properties of special concern in pathologies, for instance to the reactivity of the free HSA-Cys34 thiol group (important antioxidative thiol pool in plasma), and to the affinity for binding of molecules and ions (for example cobalt as a prominent biomarker in heart ischemia). Therefore, the method for determination of FAs bound to HSA was developed. FAs were released from HSA (previously isolated from serum by ammonium sulfate precipitation) using acidic copper(II) sulfate in phosphoric acid, extracted by n-heptane-chloroform (4:1, v/v) mixture, spotted on TL silica-gel and then developed with n-heptane-chloroform-acetic acid (5:3:0.3, v/v/v). Common office flatbed scanner and software solution for densitometric image analysis, developed in R, were used. The linearity of calibration curve in concentration range from 0.1 to 5.0mmol/L stearic acid was achieved. The method was proved to be precise (with RSD of 1.4-4.7%) and accurate. Accuracy was examined by standard addition method (recoveries 97.2-102.5%) and by comparison to results of GC. The method is sample saving, technically less demanding, and cheap, and therefore suitable for determination of FAs/HSA ratio when elevated concentrations of free FAs are reliable diagnostic/risk parameter of pathological states. PMID:27394177

  3. Neonatal jaundice: a critical review of the role and practice of bilirubin analysis.

    PubMed

    Kirk, Jean M

    2008-09-01

    Neonatal jaundice is common, and usually harmless, because of physiological jaundice or breast-feeding. In some neonates unconjugated bilirubin concentration, coupled with other risk factors, is sufficient to allow free bilirubin to cross the blood-brain barrier and cause kernicterus. Another subgroup of infants is jaundiced because of elevated conjugated bilirubin; a marker for a number of pathological conditions. Bilirubin measurement must identify those infants at risk. Transcutaneous bilirubin measurement is increasingly used in healthy infants, especially before early discharge or at home, to assess the need for laboratory bilirubin measurement. Transcutaneous measurements are not covered by laboratory quality assessment schemes. Guidelines on management of neonatal jaundice utilize age in hours and other risk factors to define bilirubin action thresholds, which may be as low as 100 micromol/L for sick premature infants, whereas early discharged babies may only present after bilirubin concentrations are extremely high. Hence, there is a requirement for accurate total bilirubin measurement from <100 to >500 micromol/L, with sufficient precision to assess the rate of bilirubin change with time. Babies presenting with late jaundice always require conjugated bilirubin measurement. It is of concern that many total and direct bilirubin automated kit methods suffer from haemolysis interference, while use of in-house methods or modification of commercial methods has virtually disappeared. External quality assessment has a vital role in providing data on different methods' performance, including accuracy, precision and susceptibility to interference. Laboratories should consider whether their adult bilirubin methods are suitable for neonates. PMID:18753416

  4. Binding of dapsone and its analogues to human serum albumin.

    PubMed

    Karp, W B; Subramanyam, S B; Robertson, A F

    1985-06-01

    The binding of dapsone, 4,4'-sulfonylbis(aniline)(1), and its diacetylated derivative, 4,4"'-sulfonylbis(acetanilide)(2), to human serum albumin is reported. To assess the ability of these compounds to displace 4'-[(4-aminophenyl)sulfonyl]acetanilide (3) from albumin, a dialysis rate technique was used. Competition for the bilirubin binding site on albumin was measured with the peroxidase assay. Compounds 1 and 2 strongly displaced both 3 and bilirubin from human serum albumin. The association constants for 1 and 2 with respect to bilirubin binding were 1.29 X 10(3) and 1.15 X 10(4) M-1, respectively. These results suggest that the binding site for 3 and the bilirubin binding site are similar with respect to 1 and 2 and that the binding of dapsone and its derivatives probably does not involve the amino function. PMID:4020658

  5. Studies on the interaction of total saponins of panax notoginseng and human serum albumin by Fourier transform infrared spectroscopy

    NASA Astrophysics Data System (ADS)

    Liu, Yuan; Xie, Meng-Xia; Kang, Juan; Zheng, Dong

    2003-10-01

    Total saponins of panax notoginseng (TPNS), isolated from the roots of panax notoginseng (Burk) F.H. Chen, have been considered as the main active components of San-Chi and have various therapeutical actions. Their interactions with human serum albumin have been investigated by Fourier transformed infrared spectrometry and fluorescence methods. The results showed that TPNS combined with HSA through C=O and CN groups of polypeptide chain. The drug-protein combination caused the significant loss of α-helix structure and the microenvironment changes of the tyrosine residues in protein at higher drug concentration. Combining the curve-fitting results of amide I and amide III bands, the alterations of protein secondary structure after drug complexation were quantitatively determined. The α-helix structure has a decrease of ≈6%, from 55 to 49% and the β-sheet increased ≈3%, from 23 to 26% at high drug concentration. However, no major alterations were observed for the β-turn and random coil structures up on drug-protein binding.

  6. Bilirubin present in diverse angiosperms

    PubMed Central

    Pirone, Cary; Johnson, Jodie V.; Quirke, J. Martin E.; Priestap, Horacio A.; Lee, David

    2010-01-01

    Background and aims Bilirubin is an orange-yellow tetrapyrrole produced from the breakdown of heme by mammals and some other vertebrates. Plants, algae and cyanobacteria synthesize molecules similar to bilirubin, including the protein-bound bilins and phytochromobilin which harvest or sense light. Recently, we discovered bilirubin in the arils of Strelitzia nicolai, the White Bird of Paradise Tree, which was the first example of this molecule in a higher plant. Subsequently, we identified bilirubin in both the arils and the flowers of Strelitzia reginae, the Bird of Paradise Flower. In the arils of both species, bilirubin is present as the primary pigment, and thus functions to produce colour. Previously, no tetrapyrroles were known to generate display colour in plants. We were therefore interested in determining whether bilirubin is broadly distributed in the plant kingdom and whether it contributes to colour in other species. Methodology In this paper, we use HPLC/UV and HPLC/UV/electrospray ionization-tandem mass spectrometry (HPLC/UV/ESI-MS/MS) to search for bilirubin in 10 species across diverse angiosperm lineages. Principal results Bilirubin was present in eight species from the orders Zingiberales, Arecales and Myrtales, but only contributed to colour in species within the Strelitziaceae. Conclusions The wide distribution of bilirubin in angiosperms indicates the need to re-assess some metabolic details of an important and universal biosynthetic pathway in plants, and further explore its evolutionary history and function. Although colour production was limited to the Strelitziaceae in this study, further sampling may indicate otherwise. PMID:22476078

  7. Association of abnormal plasma bilirubin with aggressive hepatocellular carcinoma phenotype.

    PubMed

    Carr, Brian I; Guerra, Vito; Giannini, Edoardo G; Farinati, Fabio; Ciccarese, Francesca; Ludovico Rapaccini, Gian; Di Marco, Maria; Benvegnù, Luisa; Zoli, Marco; Borzio, Franco; Caturelli, Eugenio; Chiaramonte, Maria; Trevisani, Franco

    2014-04-01

    Cirrhosis-related abnormal liver function is associated with predisposition to hepatocellular carcinoma (HCC). It features in several HCC classification systems and is an HCC prognostic factor. The aim of the present study was to examine the phenotypic tumor differences in HCC patients with normal or abnormal plasma bilirubin levels. A 2,416-patient HCC cohort was studied and dichotomized into normal and abnormal plasma bilirubin groups. Their HCC characteristics were compared for tumor aggressiveness features, namely, blood alpha-fetoprotein (AFP) levels, tumor size, presence of portal vein thrombosis (PVT) and tumor multifocality. In the total cohort, elevated bilirubin levels were associated with higher AFP levels, increased PVT and multifocality, and lower survival, despite similar tumor sizes. When different tumor size terciles were compared, similar results were found, even among patients with small tumors. A multiple logistic regression model for PVT or tumor multifocality showed increased odds ratios for elevated levels of gamma glutamyl transpeptidase (GGTP), bilirubin, and AFP and for larger tumor sizes. We conclude that HCC patients with abnormal bilirubin levels had worse prognosis than patients with normal bilirubin. They also had an increased incidence of PVT and tumor multifocality, and higher AFP levels, in patients with both small and larger tumors. The results show an association between bilirubin levels and indices of HCC aggressiveness. PMID:24787296

  8. Association of bilirubin and malondialdehyde levels with retinopathy in type 2 diabetes mellitus

    PubMed Central

    Dave, Apoorva; Kalra, Pramila; Gowda, B. H. Rakshitha; Krishnaswamy, Malavika

    2015-01-01

    Introduction: Bilirubin as an antioxidant and malondialdehyde (MDA) as an oxidant have been shown to be associated with various complications of type 2 diabetes mellitus (DM). Aims and Objectives: The aim was to measure the levels of serum bilirubin and MDA in type 2 DM patients with and without diabetic retinopathy (DR) and to correlate them with severity of DR. Materials and Methods: A total number of 120 subjects out of which 40 were controls without type 2 DM and the rest 80 were type 2 DM patients were included in the study. Of those 80 diabetics, 44 patients did not have DR and 36 patients had DR. Results: The total bilirubin, direct bilirubin, indirect bilirubin were higher in controls as compared to cases (P = 0.017, 0.033, 0.024). Serum MDA levels were found to be higher in diabetics as compared to controls (P = 0.00). The values of all the three parameters, that is, total bilirubin, direct bilirubin and indirect bilirubin were lower in patients with retinopathy as compared to those without retinopathic changes (P = 0.00, 0.020, and 0.007). Subjects were assigned to quartiles based on serum total bilirubin concentration. The prevalence of DR was significantly lower among persons with the highest bilirubin quartile compared to those with the lowest quartile. The severity of DR was inversely proportional to the total bilirubin levels (P = 0.001). The multiple logistic regression analysis showed total bilirubin to be associated with prevalence of DR (P = 0.035). Conclusions: The levels of total bilirubin were significantly lower in patients with DR and also in the late stages of retinopathy as compared to those without retinopathy and in controls but MDA levels did not show any association with DR. PMID:25932393

  9. Acute Alcohol Consumption Elevates Serum Bilirubin, an Endogenous Antioxidant

    PubMed Central

    O’Malley, Stephanie S.; Gueorguieva, Ralitza; Wu, Ran; Jatlow, Peter I.

    2015-01-01

    Background Moderate alcohol consumption has been associated with both negative and favorable effects on health. The mechanisms responsible for reported favorable effects remain unclear. Higher (not necessarily elevated) concentrations of serum bilirubin, an antioxidant, have also been associated with reduced risk of cardiovascular disease and all-cause mortality. This study tests the hypothesis that single dose alcohol consumption elevates bilirubin providing a potential link between these observations. Methods 18 healthy individuals (8 cigarette smokers) were administered alcohol, calibrated to achieve blood concentrations of 20, 80 and 120 mg/dL, in random order in 3 laboratory sessions separated by a week. Each session was preceded by and followed by 5–7 days of alcohol abstinence. Serum bilirubin was measured at 7:45 am prior to drinking, at 2 pm, and at 7:45 the next morning. Mixed effects regression models compared baseline and 24 hr. post-drinking bilirubin concentrations. Results Total serum bilirubin (sum of indirect and direct) concentration increased significantly after drinking from baseline to 24 hours in non-smokers (from Mean=0.38, SD=0.24 to Mean=0.51 SD=0.30, F(1, 32.2) =24.24, p<.0001) but not in smokers (from Mean=0.25, SD=0.12 to Mean=0.26, SD=0.15, F(1, 31.1) =0.04, p=0.84). In nonsmokers the indirect bilirubin concentration and the ratio of indirect (unconjugated) to direct (conjugated) bilirubin also increased significantly. Conclusions Alcohol consumption leads to increases in serum bilirubin in nonsmokers. Considering the antioxidant properties of bilirubin, our findings suggest one possible mechanism for the reported association between alcohol consumption and reduced risk of some disorders that could be tested in future longitudinal studies. PMID:25707709

  10. Effects of aluminum chloride on serum proteins, bilirubin, and hepatic trace elements in chickens.

    PubMed

    Wang, Ben; Zhu, Yanzhu; Zhang, Hongling; Liu, Liming; Li, Guojiang; Song, Yongli; Li, Yanfei

    2016-09-01

    The aim of this study was to reveal the effects of aluminum chloride (AlCl3) on the hepatic metabolism function and trace elements' distribution. Two hundred healthy male chickens (1 day old) were intraperitoneally administered with AlCl3 (0, 18.31, 27.47, and 36.62 mg kg(-1) day(-1) of Al(3+)) consecutively for 3 days. Then the chickens were allowed to rest for 1 day. The cycle lasted four days. The cycle was repeated 15 times (60 days). The contents of serum total protein (TP), albumin (ALB), total bilirubin (TBI), direct bilirubin (DBI), hepatic aluminum (Al), copper (Cu), iron (Fe), and zinc (Zn) were examined. The results showed that the contents of serum TP and ALB and hepatic Fe and Zn decreased and the contents of serum TBI and DBI and hepatic Al and Cu increased in the chickens with AlCl3 This indicates that chronic administration of AlCl3 impairs the hepatic metabolism function and disorders the hepatic trace elements' distribution. PMID:25896954

  11. Low Serum Albumin Level, Male Sex, and Total Gastrectomy Are Risk Factors of Severe Postoperative Complications in Elderly Gastric Cancer Patients

    PubMed Central

    Kang, Sung Chan; Kim, Hyun Il

    2016-01-01

    Purpose It is well known that old age is a risk factor for postoperative complications. Therefore, this study aimed to explore the risk factors for poor postoperative surgical outcomes in elderly gastric cancer patients. Materials and Methods Between January 2006 and December 2015, 247 elderly gastric cancer patients who underwent curative gastrectomy were reviewed. In this study, an elderly patient was defined as a patient aged ≥65 years. All possible variables were used to explore the risk factors for poor early surgical outcomes in elderly gastric cancer patients. Results Based on multivariate analyses of preoperative risk factors, preoperative low serum albumin level (<3.5 g/dl) and male sex showed statistical significance in predicting severe postoperative complications. Additionally, in an analysis of surgery-related risk factors, total gastrectomy was a risk factor for severe postoperative complications. Conclusions Our study findings suggest that low serum albumin level, male sex, and total gastrectomy could be risk factors of severe postoperative complications in elderly gastric cancer patients. Therefore, surgeons should work carefully in cases of elderly gastric cancer patients with low preoperative serum albumin level and male sex. We believe that efforts should be made to avoid total gastrectomy in elderly gastric cancer patients. PMID:27104026

  12. [The significance of low levels of total proteins, albumins, globulins and complement factors in ascitic fluid and the development of spontaneous bacterial peritonitis in patients with liver cirrhosis].

    PubMed

    Ljubicić, N; Bilić, A; Babić, Z; Roić, D; Banić, M

    1992-01-01

    Spontaneous bacterial peritonitis is one of the most common complications of ascitic fluid in patients with liver cirrhosis. The aim of this study was to investigate the role of total protein, albumin, globulin and complement ascitic fluid concentrations in development of spontaneous bacterial peritonitis in patients with liver cirrhosis. In patients with liver cirrhosis and spontaneous bacterial peritonitis (n = 8) the ascitic fluid total protein, albumin and globulin concentrations were significantly lower than in patients with sterile ascites (n = 11) (p < 0.01). The ascitic fluid complement C3 and C4 concentrations were significantly lower in patients with spontaneous bacterial peritonitis than in patients with sterile ascites (9.1 +/- 3.1 mg/dL to 22.9 +/- 17.4 mg/dL, p < 0.01; 3.8 +/- 5.9 mg/dL to 8.2 +/- 5.9 mg/dL, p < 0.01, respectively). The ascites total protein, albumin, globulin and complement concentrations in cirrhotic patients with spontaneous bacterial peritonitis were significantly lower than in patients with sterile ascites demonstrating the importance of those factors in ascitic fluid defense against secondary bacterial infection. PMID:1343119

  13. Photoacoustic microscopy of bilirubin in tissue phantoms

    NASA Astrophysics Data System (ADS)

    Zhou, Yong; Zhang, Chi; Yao, Da-Kang; Wang, Lihong V.

    2012-12-01

    Determining both bilirubin's concentration and its spatial distribution are important in disease diagnosis. Here, for the first time, we applied quantitative multiwavelength photoacoustic microscopy (PAM) to detect bilirubin concentration and distribution simultaneously. By measuring tissue-mimicking phantoms with different bilirubin concentrations, we showed that the root-mean-square error of prediction has reached 0.52 and 0.83 mg/dL for pure bilirubin and for blood-mixed bilirubin detection (with 100% oxygen saturation), respectively. We further demonstrated the capability of the PAM system to image bilirubin distribution both with and without blood. Finally, by underlaying bilirubin phantoms with mouse skins, we showed that bilirubin can be imaged with consistent accuracy down to >400 μm in depth. Our results show that PAM has potential for noninvasive bilirubin monitoring in vivo, as well as for further clinical applications.

  14. [The effect of the albumin concentration on the relation between the concentration of ionized calcium and total calcium in the blood of dogs].

    PubMed

    Mischke, R; Hänies, R; Lange, K; Rivera Ramirez, P A

    1996-06-01

    Based on the results of 367 healthy dogs of different age, it could be demonstrated that the concentration of ionized calcium corrected to the pH-value of 7.4 ([Cai (7.4)]) as well as the concentration of total calcium ([Catot]) clearly decreased with increasing age. The most obvious changes were found during the first four months. The [Cai (7.4)] was not influenced distinctly by sex or by breed. The reference range (2.5-97.5% quantil) for [Cai (7.4)] in heparinized plasma was 1.32-1.51 mmol/l in 4-months- to 1-year-old dogs and 1.22-1.46 mmol/l in dogs older than one year, corresponding to a proportion of Cai to Catot of 44.9-54.9%. A moderately close correlation existed between [Cai (7.4)] and the [Catot] (r = 0.754) (n = 393 adult dogs: 180 healthy animals and 213 unselected patients). A similar correlation coefficient was found between the concentrations of Catot and albumin (r = 0.718) or total protein (r = 0.617), respectively. The proportion of Cai to Catot decreased with an increasing concentration of albumin, whereas [Cai (7.4)] tended to increase. The correction of the [Catot] for albumin did not lead to an increased correlation coefficient for the relation with [Cai (7.4)] (r = 0.676). In addition to albumin concentration, the relation between [Cai (7.4)] and the Catot is primarily influenced by complex-forming ions. This became clear by the transient citrate-induced decrease of [Cai (7.4)] whereas [Catot] increased after infusion of fresh frozen plasma in dogs suffering from diarrhea. This investigation shows the limits of the estimation of calcium homoeostasis on the basis of the [Catot]. PMID:8766900

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

    PubMed

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

    2015-01-01

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

  16. Bilirubin release induced by tumor necrosis factor in combination with galactosamine is toxic to mice.

    PubMed

    Van Molle, W; Libert, C

    2003-08-01

    Application of tumor necrosis factor (TNF) in combination with galactosamine (GalN) in mice causes severe apoptosis of hepatocytes, resulting in complete destruction of the liver. Administration of high levels of unconjugated bilirubin and abnormally high production of unconjugated bilirubin have been reported to cause liver damage and are associated with several human pathologies. Serum alanine aminotransferase as well as total and direct bilirubin levels in mice were determined. Bilirubin levels are shown to significantly increase after a challenge with TNF/GalN in mice. Pretreatment with a heme oxygenase-1 inhibitor significantly prevents this release in bilirubin and offers significant protection against TNF/GalN-induced lethality. A correlation between the release of unconjugated bilirubin and the toxicity accompanied with this release is provided. PMID:12906872

  17. 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

  18. Measurement of serum bilirubin and its mono- and diconjugates: application to patients with hepatobiliary disease.

    PubMed Central

    Scharschmidt, B F; Blanckaert, N; Farina, F A; Kabra, P M; Stafford, B E; Weisiger, R A

    1982-01-01

    A technique has recently been described by Blanckaert and his colleagues that specifically and accurately quantifies unconjugated bilirubin, diconjugated bilirubin, and the C-8 and C-12 isomers of monoconjugated bilirubin. This technique has now been used to determine the distribution pattern of bilirubin and its ester conjugates in 91 sera from 65 patients with hepatobiliary disease, and the results were compared with two conventional diazo assays. Both diazo assays yielded values for total bilirubin concentration that were markedly and unpredictably higher than those obtained by the new technique, and the direct-reacting fraction by diazo assay showed little or no agreement with the fraction of total ester conjugates determined by the new method. Previous studies using the new method had shown that bilirubin conjugates are undetectable in sera from healthy adults or individuals with Gilbert's syndrome, but they were found in 89 of the 91 present patient sera. The fraction of total serum bilirubin represented by C-8 monoconjugates, C-12 monoconjugates, diconjugates, and total ester conjugates was higher in patients with biliary obstruction than in those with parenchymal liver disease, but extensive overlap between groups prevented determination of these conjugated species from being diagnostically useful. Overall, bilirubin ester conjugates in serum consisted of 30% C-8 monoconjugates, 37% C-12 monoconjugates, and 33% diconjugates, while urine contained predominantly diconjugates. PMID:7095558

  19. Albumin administration prevents neurological damage and death in a mouse model of severe neonatal hyperbilirubinemia

    PubMed Central

    Vodret, Simone; Bortolussi, Giulia; Schreuder, Andrea B.; Jašprová, Jana; Vitek, Libor; Verkade, Henkjan J.; Muro, Andrés F.

    2015-01-01

    Therapies to prevent severe neonatal unconjugated hyperbilirubinemia and kernicterus are phototherapy and, in unresponsive cases, exchange transfusion, which has significant morbidity and mortality risks. Neurotoxicity is caused by the fraction of unconjugated bilirubin not bound to albumin (free bilirubin, Bf). Human serum albumin (HSA) administration was suggested to increase plasma bilirubin-binding capacity. However, its clinical use is infrequent due to difficulties to address its potential preventive and curative benefits, and to the absence of reliable markers to monitor bilirubin neurotoxicity risk. We used a genetic mouse model of unconjugated hyperbilirubinemia showing severe neurological impairment and neonatal lethality. We treated mutant pups with repeated HSA administration since birth, without phototherapy application. Daily intraperitoneal HSA administration completely rescued neurological damage and lethality, depending on dosage and administration frequency. Albumin infusion increased plasma bilirubin-binding capacity, mobilizing bilirubin from tissues to plasma. This resulted in reduced plasma Bf, forebrain and cerebellum bilirubin levels. We showed that, in our experimental model, Bf is the best marker to determine the risk of developing neurological damage. These results support the potential use of albumin administration in severe acute hyperbilirubinemia conditions to prevent or treat bilirubin neurotoxicity in situations in which exchange transfusion may be required. PMID:26541892

  20. Unconjugated Bilirubin and an Increased Proportion of Bilirubin Monoconjugates in the Bile of Patients with Gilbert's Syndrome and Crigler-Najjar Disease

    PubMed Central

    Fevery, Johan; Blanckaert, Norbert; Heirwegh, Karel P. M.; Préaux, Anne-Marie; Berthelot, Pierre

    1977-01-01

    Bilirubin pigments were studied in the bile of 20 normal adults, 25 patients with Gilbert's syndrome, 9 children with Crigler-Najjar disease, and 6 patients with hemolysis, to determine how a deficiency of hepatic bilirubin UDP-glucuronosyltransferase would affect the end products of bilirubin biotransformation. In the bile from patients with Gilbert's syndrome, a striking increase was found in the proportion of bilirubin monoconjugates (48.6±9.8% of total conjugates) relative to that in normal bile (27.2±7.8%). This increase was even more pronounced in children with Crigler-Najjar disease, in whom, even in the most severe cases, glucuronide could always be demonstrated in the bile. Furthermore, unconjugated bilirubin-IXα was unquestionably present in the bile of these children and amounted to 30-57% of their total bilirubin pigments (<1% in the controls). It was not possible to predict from the biliary bilirubin composition whether a child would respond to phenobarbital therapy or not. Bile composition was normal in patients with hemolysis, except when there was associated deficiency of hepatic glucuronosyltransferase. Therefore, the observed alterations were not a simple consequence of unconjugated hyperbilirubinemia. The present findings suggest that Crigler-Najjar disease represents a more pronounced expression than Gilbert's syndrome of a common biochemical defect. Hepatic bilirubin UDP-glucuronosyltransferase deficiency leads to decreased formation of diconjugates with an ensuing increase in the proportion of bilirubin monoconjugates in bile; in the most severe cases, an elevated content of biliary unconjugated bilirubin is also found. PMID:409736

  1. Comparison in different species of biliary bilirubin-IX alpha conjugates with the activities of hepatic and renal bilirubin-IX alpha-uridine diphosphate glycosyltransferases.

    PubMed Central

    Fevery, J; Van de Vijver, M; Michiels, R; Heirwegh, K P

    1977-01-01

    The bilrubin-IXalpha conjugates in bile and the activities of bilirubin-IX alpha--UDP-glycosyltransferases in liver and kidney were determined for ten species of mammals and for the chicken. 1. In the mammalian species, bilirubin-IX alpha glucuronide was the predominant bile pigment. Excretion of neutral glycosides was unimportant, except in the cat, the mouse, the rabbit and the dog, where glucose and xylose represented 12--41% of total conjugating groups bound to bilirubin-IX alpha. In chicken bile, glucoside and glucuronide conjugates were of equal importance. They probably represent only a small fraction of the total bile pigment. 2. The transferase activities in liver showed pronounced species variation. This was also apparent with regard to activation by digitonin, pH optimum and relative activities of transferases acting on either UDP-glucuronic acid or neutral UDP-sugars. 3. Man, the dog, the cat and the rat excrete bilirubin-IX alpha largely as diconjugated derivatives. In general, diconjugated bilirubin-IX alpha could also be synthesized in vitro with liver homogenate, bilirubin-IX alpha and UDP-sugar. In contrast, for the other species examined, bilirubin pigments consisted predominantly of monoconjugated bilirubin-IX alpha. Synthesis in vitro with UDP-glucuronic acid, UDP-glucose or UDP-xylose as the sugar donor led exclusively to the formation of monoconjugated bilirubin-IX alpha. 4. The transferase activities in the kidney were restricted to the cortex and were important only for the rat and the dog. No activity at all could be detected for several species, including man. 5. Comparison of the transferase activities in liver with reported values of the maximal rate of excretion in bile suggests a close linkage between conjugation and biliary secretion of bilirubin-IX alpha. PMID:407905

  2. Bilirubin-Induced Audiologic Injury in Preterm Infants.

    PubMed

    Olds, Cristen; Oghalai, John S

    2016-06-01

    Although hyperbilirubinemia is extremely common among neonates and is usually mild and transient, it sometimes leads to bilirubin-induced neurologic damage (BIND). The auditory pathway is highly sensitive to the effects of elevated total serum/plasma bilirubin (TB) levels, with damage manifesting clinically as auditory neuropathy spectrum disorder. Compared to full-term neonates, preterm neonates are more susceptible to BIND and suffer adverse effects at lower TB levels with worse long-term outcomes. Furthermore, although standardized guidelines for management of hyperbilirubinemia exist for term and late preterm neonates, similar guidelines for neonates less than 35 weeks gestational age are limited. PMID:27235210

  3. Malnutrition in Alzheimer’s Disease, Dementia with Lewy Bodies, and Frontotemporal Lobar Degeneration: Comparison Using Serum Albumin, Total Protein, and Hemoglobin Level

    PubMed Central

    Hashimoto, Mamoru; Tanaka, Hibiki; Fujise, Noboru; Matsushita, Masateru; Miyagawa, Yusuke; Hatada, Yutaka; Fukuhara, Ryuji; Hasegawa, Noriko; Todani, Shuji; Matsukuma, Kengo; Kawano, Michiyo; Ikeda, Manabu

    2016-01-01

    Malnutrition among dementia patients is an important issue. However, the biochemical markers of malnutrition have not been well studied in this population. The purpose of this study was to compare biochemical blood markers among patients with Alzheimer’s disease (AD), dementia with Lewy bodies (DLB), and frontotemporal lobar degeneration (FTLD). A total of 339 dementia outpatients and their family caregivers participated in this study. Low serum albumin was 7.2 times more prevalent among patients with DLB and 10.1 times more prevalent among those with FTLD than among those with AD, with adjustment for age. Low hemoglobin was 9.1 times more common in female DLB patients than in female AD patients, with adjustment for age. The levels of biochemical markers were not significantly correlated with cognitive function. Family caregivers of patients with low total protein, low albumin, or low hemoglobin were asked if the patients had loss of weight or appetite; 96.4% reported no loss of weight or appetite. In conclusion, nutritional status was worse in patients with DLB and FTLD than in those with AD. A multidimensional approach, including blood testing, is needed to assess malnutrition in patients with dementia. PMID:27336725

  4. Surface-modified anodic aluminum oxide membrane with hydroxyethyl celluloses as a matrix for bilirubin removal.

    PubMed

    Xue, Maoqiang; Ling, Yisheng; Wu, Guisen; Liu, Xin; Ge, Dongtao; Shi, Wei

    2013-01-01

    Microporous anodic aluminum oxide (AAO) membranes were modified by 3-glycidoxypropyltrimethoxysilane to produce terminal epoxy groups. These were used to covalently link hydroxyethyl celluloses (HEC) to amplify reactive groups of AAO membrane. The hydroxyl groups of HEC-AAO composite membrane were further modified with 1,4-butanediol diglycidyl ether to link arginine as an affinity ligand. The contents of HEC and arginine of arginine-immobilized HEC-AAO membrane were 52.1 and 19.7mg/g membrane, respectively. As biomedical adsorbents, the arginine-immobilized HEC-AAO membranes were tested for bilirubin removal. The non-specific bilirubin adsorption on the unmodified HEC-AAO composite membranes was 0.8mg/g membrane. Higher bilirubin adsorption values, up to 52.6mg/g membrane, were obtained with the arginine-immobilized HEC-AAO membranes. Elution of bilirubin showed desorption ratio was up to 85% using 0.3M NaSCN solution as the desorption agent. Comparisons equilibrium and dynamic capacities showed that dynamic capacities were lower than the equilibrium capacities. In addition, the adsorption mechanism of bilirubin and the effects of temperature, initial concentration of bilirubin, albumin concentration and ionic strength on adsorption were also investigated. PMID:23290920

  5. Bilirubin Binding to PPARα Inhibits Lipid Accumulation.

    PubMed

    Stec, David E; John, Kezia; Trabbic, Christopher J; Luniwal, Amarjit; Hankins, Michael W; Baum, Justin; Hinds, Terry D

    2016-01-01

    Numerous clinical and population studies have demonstrated that increased serum bilirubin levels protect against cardiovascular and metabolic diseases such as obesity and diabetes. Bilirubin is a potent antioxidant, and the beneficial actions of moderate increases in plasma bilirubin have been thought to be due to the antioxidant effects of this bile pigment. In the present study, we found that bilirubin has a new function as a ligand for PPARα. We show that bilirubin can bind directly to PPARα and increase transcriptional activity. When we compared biliverdin, the precursor to bilirubin, on PPARα transcriptional activation to known PPARα ligands, WY 14,643 and fenofibrate, it showed that fenofibrate and biliverdin have similar activation properties. Treatment of 3T3-L1 adipocytes with biliverdin suppressed lipid accumulation and upregulated PPARα target genes. We treated wild-type and PPARα KO mice on a high fat diet with fenofibrate or bilirubin for seven days and found that both signal through PPARα dependent mechanisms. Furthermore, the effect of bilirubin on lowering glucose and reducing body fat percentage was blunted in PPARα KO mice. These data demonstrate a new function for bilirubin as an agonist of PPARα, which mediates the protection from adiposity afforded by moderate increases in bilirubin. PMID:27071062

  6. Bilirubin Binding to PPARα Inhibits Lipid Accumulation

    PubMed Central

    Stec, David E.; John, Kezia; Trabbic, Christopher J.; Luniwal, Amarjit; Hankins, Michael W.; Baum, Justin

    2016-01-01

    Numerous clinical and population studies have demonstrated that increased serum bilirubin levels protect against cardiovascular and metabolic diseases such as obesity and diabetes. Bilirubin is a potent antioxidant, and the beneficial actions of moderate increases in plasma bilirubin have been thought to be due to the antioxidant effects of this bile pigment. In the present study, we found that bilirubin has a new function as a ligand for PPARα. We show that bilirubin can bind directly to PPARα and increase transcriptional activity. When we compared biliverdin, the precursor to bilirubin, on PPARα transcriptional activation to known PPARα ligands, WY 14,643 and fenofibrate, it showed that fenofibrate and biliverdin have similar activation properties. Treatment of 3T3-L1 adipocytes with biliverdin suppressed lipid accumulation and upregulated PPARα target genes. We treated wild-type and PPARα KO mice on a high fat diet with fenofibrate or bilirubin for seven days and found that both signal through PPARα dependent mechanisms. Furthermore, the effect of bilirubin on lowering glucose and reducing body fat percentage was blunted in PPARα KO mice. These data demonstrate a new function for bilirubin as an agonist of PPARα, which mediates the protection from adiposity afforded by moderate increases in bilirubin. PMID:27071062

  7. Adsorption of bovine serum albumin (BSA) onto lecithin studied by attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy.

    PubMed

    Tantipolphan, R; Rades, T; McQuillan, A J; Medlicott, N J

    2007-06-01

    The adsorption of bovine serum albumin (BSA) to lecithin was investigated by ATR-FTIR spectroscopy. Lecithin films were prepared by casting aliquots of 3.2 microg lecithin in methanol onto ZnSe ATR prisms. Surface morphology and the thickness of the films were investigated by laser scanning confocal electron microscopy and scanning electron microscopy and the thickness of the films used for adsorption studies was estimated to be 40 A. The dependency of the CO peak area on the lecithin mass in the calibration curve confirms that the thickness of the film is below the penetration depth of the infrared evanescent wave. Size exclusion HPLC and fluorescence spectroscopy show that BSA conformation in up to 1M NaCl and CaCl(2) solutions is similar to that in water with no aggregation or changes in protein conformation seen over 4h. The kinetics of BSA adsorption on the lecithin film from water, NaCl and CaCl(2) solutions demonstrates that ions promote the protein adsorption. BSA bound more in the presence of NaCl compared to CaCl(2) at equivalent concentrations. The adsorption appeared greatest at a 0.1M concentration for both NaCl and CaCl(2). The results are explained in terms of absorptive reactivity of BSA and lecithin surfaces upon salt addition. PMID:17240095

  8. Bilirubin and Its Carbohydrate Conjugates

    NASA Astrophysics Data System (ADS)

    Blanckaert, Norbert J. C.

    In mammals, the open tetrapyrrole bilirubin (structure 2, Fig. 1) is the principal degradation product of iron-protoporphyrin-IX (heme). The latter molecule is a tetrapyrrolic macrocycle and plays a critical role in aerobic metabolism by reversibly binding oxygen in hemoglobin and myoglobin, and by serving as the active site in oxidation reactions catalyzed by hemoprotein enzymes. Important cyclic tetrapyrroles in nature related to heme are chlorophylls, which contain magnesium and are derived from protoporphyrin-IX, and vitamin B12, a corrinoid derived from uroporphyrinogen-III.

  9. Albumin Test

    MedlinePlus

    ... to a variety of conditions in addition to malnutrition , a decrease in albumin needs to be evaluated ... can also be seen in inflammation , shock, and malnutrition . They may be seen with conditions in which ...

  10. 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.

  11. Serum albumin levels in burn people are associated to the total body surface burned and the length of hospital stay but not to the initiation of the oral/enteral nutrition

    PubMed Central

    Pérez-Guisado, Joaquín; de Haro-Padilla, Jesús M; Rioja, Luis F; DeRosier, Leo C; de la Torre, Jorge I

    2013-01-01

    Objective: Serum albumin levels have been used to evaluate the severity of the burns and the nutrition protein status in burn people, specifically in the response of the burn patient to the nutrition. Although it hasn’t been proven if all these associations are fully funded. The aim of this retrospective study was to determine the relationship of serum albumin levels at 3-7 days after the burn injury, with the total body surface area burned (TBSA), the length of hospital stay (LHS) and the initiation of the oral/enteral nutrition (IOEN). Subject and methods: It was carried out with the health records of patients that accomplished the inclusion criteria and were admitted to the burn units at the University Hospital of Reina Sofia (Córdoba, Spain) and UAB Hospital at Birmingham (Alabama, USA) over a 10 years period, between January 2000 and December 2009. We studied the statistical association of serum albumin levels with the TBSA, LHS and IOEN by ANOVA one way test. The confidence interval chosen for statistical differences was 95%. Duncan’s test was used to determine the number of statistically significantly groups. Results: Were expressed as mean±standard deviation. We found serum albumin levels association with TBSA and LHS, with greater to lesser serum albumin levels found associated to lesser to greater TBSA and LHS. We didn’t find statistical association with IOEN. Conclusion: We conclude that serum albumin levels aren’t a nutritional marker in burn people although they could be used as a simple clinical tool to identify the severity of the burn wounds represented by the total body surface area burned and the lenght of hospital stay. PMID:23875122

  12. The quantitative effect of serum albumin, serum urea, and valproic acid on unbound phenytoin concentrations in children.

    PubMed

    ter Heine, Rob; van Maarseveen, Erik M; van der Westerlaken, Monique M L; Braun, Kees P J; Koudijs, Suzanne M; Berg, Maarten J Ten; Malingré, Mirte M

    2014-06-01

    Dosing of phenytoin is difficult in children because of its variable pharmacokinetics and protein binding. Possible covariates for this protein binding have mostly been univariately investigated in small, and often adult, adult populations. We conducted a study to identify and quantify these covariates in children. We extracted data on serum phenytoin concentrations, albumin, triglycerides, urea, total bilirubin and creatinine concentrations and data on coadministration of valproic acid or carbamazepine in 186 children. Using nonlinear mixed effects modeling the effects of covariates on the unbound phenytoin fraction were investigated. Serum albumin, serum urea concentrations, and concomitant valproic acid use significantly influenced the unbound phenytoin fraction. For clinical practice, we recommend that unbound phenytoin concentrations are measured routinely. However, if this is impossible, we suggest to use our model to calculate the unbound concentration. In selected children, close treatment monitoring and dose reductions should be considered to prevent toxicity. PMID:23670246

  13. Determination of bilirubin glucuronide and assay of glucuronyltransferase with bilirubin as acceptor

    PubMed Central

    Van Roy, F. P.; Heirwegh, K. P. M.

    1968-01-01

    1. Conjugated bilirubin is conveniently determined by coupling with the diazonium salt of ethyl anthranilate. 2. This method has been used in the development of assays for UDP-glucuronyltransferase (EC 2.4.1.17), with bilirubin as substrate, in rat liver homogenates, microsomal preparations and partly purified fractions. 3. Chromatographic analysis suggests that bilirubin monoglucuronide is the product of the enzyme systems studied. PMID:5660631

  14. Association of Serum Bilirubin with SYNTAX Score and Future Cardiovascular Events in Patients Undergoing Coronary Intervention

    PubMed Central

    Chang, Chun-Chin; Hsu, Chien-Yi; Huang, Po-Hsun; Chiang, Chia-Hung; Huang, Shao-Sung; Leu, Hsin-Bang; Huang, Chin-Chou; Chen, Jaw-Wen; Lin, Shing-Jong

    2016-01-01

    Background Bilirubin has emerged as an important endogenous antioxidant molecule, and increasing evidence shows that bilirubin may protect against atherosclerosis. The SYNTAX score has been developed to assess the severity and complexity of coronary artery disease. The aim of this study was to evaluate whether serum bilirubin levels are associated with SYNTAX scores and whether they could be used to predict future cardiovascular events in patients undergoing coronary intervention. Methods Serum bilirubin levels and other blood parameters in patients with at least 12-h fasting states were determined. The primary endpoint was any composite cardiovascular event within 1 year, including death, nonfatal myocardial infarction, and target-vessel revascularization. Results In total, 250 consecutive patients with stable coronary artery disease (mean age 70 ± 13) who had received coronary intervention were enrolled. All study subjects were divided into two groups: group 1 was defined as high SYNTAX score (> 22), and group 2 was defined as low SYNTAX score (≤ 22). Total bilirubin levels were significantly lower in the high SYNTAX score group than in the low SYNTAX score group (0.51 ± 0.22 vs. 0.72 ± 0.29 mg/dl, p < 0.001). By multivariate analysis, serum total bilirubin levels were identified as an independent predictor for high SYNTAX score (adjusted odds ratio: 0.28, 95% confidence interval 0.04-0.42; p = 0.004). Use of the Kaplan-Meier analysis demonstrated a significant difference in 1-year cardiovascular events between high (> 0.8 mg/dl), medium (> 0.5, ≤ 0.8 mg/dl), and low (≤ 0.5 mg/dl) bilirubin levels (log-rank test p = 0.011). Conclusions Serum bilirubin level is associated with SYNTAX score and predicts future cardiovascular events in patients undergoing coronary intervention. PMID:27471354

  15. Bilirubin as a potential causal factor in type 2 diabetes risk: a Mendelian randomization study

    PubMed Central

    Abbasi, Ali; Deetman, Petronella E.; Corpeleijn, Eva; Gansevoort, Ron T.; Gans, Rijk O.B.; Hillege, Hans L.; van der Harst, Pim; Stolk, Ronald P.; Navis, Gerjan; Alizadeh, Behrooz Z.; Bakker, Stephan J.L.

    2014-01-01

    Circulating bilirubin, a natural antioxidant, is associated with decreased risk of type 2 diabetes (T2D), but the nature of the relationship remains unknown. We performed Mendelian randomization in a prospective cohort of 3,381 participants free of diabetes at baseline (aged 28-75 years; women, 52.6%). We used rs6742078 located in UDP-glucuronosyltransferase (UGT1A1) locus as instrumental variable (IV) to study a potential causal effect of serum total bilirubin on T2D risk. T2D developed in a total of 210 (6.2%) participants during a median follow-up of 7.8 years. In adjusted analyses, rs6742078, which explained 19.5% of bilirubin variation, was strongly associated with total bilirubin (a 0.68-SD increase in bilirubin levels per T allele; P<1×10−122) and was also associated with T2D risk (OR 0.69 [95%CI, 0.54-0.90]; P=0.006). Per 1-SD increase in log-transformed bilirubin levels, we observed a 25% (OR 0.75 [95%CI, 0.62-0.92]; P=0.004) lower risk of T2D. In Mendelian randomization analysis, the causal risk reduction for T2D was estimated to be 42% (causal ORIVestimation per 1-SD increase in log-transformed bilirubin 0.58 [95%CI, 0.39-0.84]; P=0.005), which was comparable to the observational estimate (Durbin-Wu-Hausman chi-square test Pfor difference =0.19). These novel results provide evidence that elevated bilirubin is causally associated with risk of T2D and support its role as a protective determinant. PMID:25368098

  16. Influence of glutathione S-transferase B (ligandin) on the intermembrane transfer of bilirubin. Implications for the intracellular transport of nonsubstrate ligands in hepatocytes.

    PubMed Central

    Zucker, S D; Goessling, W; Ransil, B J; Gollan, J L

    1995-01-01

    To examine the hypothesis that glutathione S-transferases (GST) play an important role in the hepatocellular transport of hydrophobic organic anions, the kinetics of the spontaneous transfer of unconjugated bilirubin between membrane vesicles and rat liver glutathione S-transferase B (ligandin) was studied, using stopped-flow fluorometry. Bilirubin transfer from glutathione S-transferase B to phosphatidylcholine vesicles was best described by a single exponential function, with a rate constant of 8.0 +/- 0.7 s-1 (+/- SD) at 25 degrees C. The variations in transfer rate with respect to acceptor phospholipid concentration provide strong evidence for aqueous diffusion of free bilirubin. This finding was verified using rhodamine-labeled microsomal membranes as acceptors. Bilirubin transfer from phospholipid vesicles to GST also exhibited diffusional kinetics. Thermodynamic parameters for bilirubin dissociation from GST were similar to those for human serum albumin. The rate of bilirubin transfer from rat liver basolateral plasma membranes to acceptor vesicles in the presence of glutathione S-transferase B declined asymptotically with increasing GST concentration. These data suggest that glutathione S-transferase B does not function as an intracellular bilirubin transporter, although expression of this protein may serve to regulate the delivery of bilirubin, and other nonsubstrate ligands, to sites of metabolism within the cell. Images PMID:7560084

  17. Intermolecular interactions in the bilirubin-cholate-silica system

    NASA Astrophysics Data System (ADS)

    Vlasova, N. N.; Golovkova, L. P.; Severinovskaya, O. V.

    2007-06-01

    Bilirubin-cholate interactions in aqueous solutions were studied. The constants of binding of bilirubin with taurocholate dimers and taurodeoxycholate trimers were calculated. The adsorption of bilirubin and cholates on the surface of highly dispersed silica was studied. It was shown that taurine-conjugated cholates are poorly adsorbed from micellar solutions on the silica surface, the specific amount of bilirubin adsorbed decreases with increasing concentration of cholates in the solution, the affinity of free bilirubin for the silica surface is independent of the nature of the cholic acid, and that the affinity of cholate-bilirubin complexes for the silica surface is lower than the affinity of free bilirubin.

  18. Sensitizing effect of Z,Z-bilirubin IXα and its photoproducts on enzymes in model solutions

    NASA Astrophysics Data System (ADS)

    Plavskii, V. Yu.; Mostovnikov, V. A.; Tret'yakova, A. I.; Mostovnikova, G. R.

    2008-05-01

    In model systems, we have studied side effects which may be induced by light during phototherapy of hyperbilirubinemia (jaundice) in newborn infants, with the aim of reducing the Z,Z-bilirubin IXα (Z,Z-BR IXα) level. We have shown that the sensitizing effect of Z,Z-BR IXα, localized at strong binding sites of the human serum albumin (HSA) macromolecule, is primarily directed at the amino acid residues of the carrier protein and does not involve the molecules of the enzyme (lactate dehydrogenase (LDH)) present in the buffer solution. The detected photodynamic damage to LDH is due to sensitization by bilirubin photoisomers, characterized by lower HSA association constants and located (in contrast to native Z,Z-BR IXα) on the surface of the HSA protein globule. Based on study of the spectral characteristics of the photoproducts of Z,Z-BR IXα and comparison of their accumulation kinetics in solution and the enzyme photo-inactivation kinetics, we concluded that the determining role in sensitized damage to LDH is played by lumirubin. The photosensitization effect depends on the wavelength of the radiation used for photoconversion of bilirubin. When (at the beginning of exposure) we make sure that identical numbers of photons are absorbed by the pigment in the different spectral ranges, the side effect is minimal for radiation corresponding to the long-wavelength edge of the bilirubin absorption band. We have shown that for a bilirubin/HSA concentration ratio >2 (when some of the pigment molecules are sorbed on the surface of the protein globule), the bilirubin can act as a photosensitizing agent for the enzyme present in solution. We discuss methods for reducing unfavorable side effects of light on the body of newborn infants during phototherapy of hyperbilirubinemia.

  19. Association between bilirubin and risk of Non-Alcoholic Fatty Liver Disease based on a prospective cohort study.

    PubMed

    Tian, Jianbo; Zhong, Rong; Liu, Cheng; Tang, Yuhan; Gong, Jing; Chang, Jiang; Lou, Jiao; Ke, Juntao; Li, Jiaoyuan; Zhang, Yi; Yang, Yang; Zhu, Ying; Gong, Yajie; Xu, Yanyan; Liu, Peiyi; Yu, Xiao; Xiao, Lin; Du, Min; Yang, Ling; Yuan, Jing; Wang, Youjie; Chen, Weihong; Wei, Sheng; Liang, Yuan; Zhang, Xiaomin; He, Meian; Wu, Tangchun; Yao, Ping; Miao, Xiaoping

    2016-01-01

    The study aimed to assess the association between total, direct, and indirect bilirubin and nonalcoholic fatty live disease (NAFLD) risk given its high prevalence and serious clinical prognosis. Among 27,009 subjects who participated in a healthy screening program from the Dongfeng-Tongji cohort study in 2008, 8189 eligible subjects (aged 35-86 years; males, 43.95%) were ultimately enrolled. The incidence rates of NAFLD in 2013 were compared with respect to baseline bilirubin levels among subjects free of NAFLD, and the effect sizes were estimated by logistic regression analysis. During 5 years follow-up, we observed 1956 cases of newly developed NAFLD with the overall incidence of 23.88%. Direct bilirubin was presented to inversely associate with NAFLD risk. Compared with quartile 1 of direct bilirubin, the multivariable-adjusted ORs (95% CIs) for NAFLD of quartile 2 to 4 were 1.104 (0.867-1.187), 0.843 (0.719-0.989), and 0.768 (0.652-0.905), respectively, P for trend 0.002). Similarly, inverse effects of direct bilirubin on NAFLD incidence were also observed when stratified by sex and BMI. However, no significant associations were found between total, and indirect bilirubin and NAFLD risk. Direct bilirubin reduced NAFLD risk independent of possible confounders among middle-aged and elderly Chinese population, probably based on the endogenous antioxidation of bilirubin. PMID:27484402

  20. Association between bilirubin and risk of Non-Alcoholic Fatty Liver Disease based on a prospective cohort study

    PubMed Central

    Tian, Jianbo; Zhong, Rong; Liu, Cheng; Tang, Yuhan; Gong, Jing; Chang, Jiang; Lou, Jiao; Ke, Juntao; Li, Jiaoyuan; Zhang, Yi; Yang, Yang; Zhu, Ying; Gong, Yajie; Xu, Yanyan; Liu, Peiyi; Yu, Xiao; Xiao, Lin; Du, Min; Yang, Ling; Yuan, Jing; Wang, Youjie; Chen, Weihong; Wei, Sheng; Liang, Yuan; Zhang, Xiaomin; He, Meian; Wu, Tangchun; Yao, Ping; Miao, Xiaoping

    2016-01-01

    The study aimed to assess the association between total, direct, and indirect bilirubin and nonalcoholic fatty live disease (NAFLD) risk given its high prevalence and serious clinical prognosis. Among 27,009 subjects who participated in a healthy screening program from the Dongfeng-Tongji cohort study in 2008, 8189 eligible subjects (aged 35–86 years; males, 43.95%) were ultimately enrolled. The incidence rates of NAFLD in 2013 were compared with respect to baseline bilirubin levels among subjects free of NAFLD, and the effect sizes were estimated by logistic regression analysis. During 5 years follow-up, we observed 1956 cases of newly developed NAFLD with the overall incidence of 23.88%. Direct bilirubin was presented to inversely associate with NAFLD risk. Compared with quartile 1 of direct bilirubin, the multivariable-adjusted ORs (95% CIs) for NAFLD of quartile 2 to 4 were 1.104 (0.867–1.187), 0.843 (0.719–0.989), and 0.768 (0.652–0.905), respectively, P for trend 0.002). Similarly, inverse effects of direct bilirubin on NAFLD incidence were also observed when stratified by sex and BMI. However, no significant associations were found between total, and indirect bilirubin and NAFLD risk. Direct bilirubin reduced NAFLD risk independent of possible confounders among middle-aged and elderly Chinese population, probably based on the endogenous antioxidation of bilirubin. PMID:27484402

  1. The origins and kinetics of bilirubin in dogs with hepatobiliary and haemolytic diseases.

    PubMed

    Rothuizen, J; van den Brom, W E; Fevery, J

    1992-05-01

    In 35 dogs with spontaneous hepatobiliary liver disease the kinetics and the sources of bilirubin were quantified. The disorders were extrahepatic bile duct obstruction (n = 4), fulminant hepatitis (n = 2), (sub)acute hepatitis (n = 5), chronic active hepatitis (CAH) with cirrhosis (n = 6), hepatic lymphosarcoma (n = 5), centrizonal necrosis secondary to haemolytic anaemia (n = 6) and other (n = 2). The plasma disappearance of [3H]bilirubin was analyzed with a two-compartment model in all dogs. The ratio early labeled/late labeled bilirubin was determined by measuring the incorporation of [14C]glycine into erythrocyte haem and faecal stercobilin. By introducing this relation in the model analysis the bilirubin production rates from erythrocyte destruction (PE), ineffective erythropoiesis (PI) and hepatic haemoprotein (PL) could be quantified. Total bilirubin turnover was increased in both primary haemolytic disease and most cases of hepatobiliary disease. Erythrocyte survival was reduced in all cases but one. The bilirubin clearance was impaired to 30-50% of the normal value in most cases of hepatobiliary disease and also in primary haemolysis. In dogs with fulminant hepatitis, and cirrhosis with or without CAH, the clearance rates were reduced to values below 15% of normal. In these dogs both an impaired clearance and an increased production were important determinants of hyperbilirubinaemia. In other cases plasma bilirubin was primarily determined by increased production. These clearances and production rates were similar in haemolysis and in many cases of primary hepatobiliary disease. The hepatic haemoprotein turnover was quite variable in all subgroups, ranging from 1-74% of the total bilirubin turnover.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1506635

  2. Micropinocytic Ingestion of Glycosylated Albumin by Isolated Microvessels: Possible Role in Pathogenesis of Diabetic Microangiopathy

    NASA Astrophysics Data System (ADS)

    Williams, Stuart K.; Devenny, James J.; Bitensky, Mark W.

    1981-04-01

    Microvessels isolated from rat epididymal fat exhibit differential vesicular ingestion rates for unmodified and nonenzymatically glycosylated rat albumin. While unmodified rat albumin is excluded from ingestion by endothelial micropinocytic vesicles, glycosylated albumin is avidly taken up by endocytosis. Interaction of albumin and glycosylated albumin with endothelium was studied with a double-label fluorescence assay of micropinocytosis. When glycosylated albumin was present at a concentration of 6% with respect to total albumin (the level found in ``non diabetic'' serum), only glycosylated albumin was ingested. At higher concentrations of glycosylated albumin (those found in diabetic serum), both albumin and glycosylated albumin are ingested. Glycosylation of endothelial membrane components results in stimulated ingestion of glycosylated albumin, persistent exclusion of unmodified albumin, and unaltered micropinocytic ingestion of native ferritin. These results indicate that nonenzymatic glycosylation of serum albumin may result in rapid vesicle-mediated extravasation of albumin. Chronic microvascular leakage of glycosylated albumin could contribute to the pathogenesis of diabetic microangiopathy.

  3. Association of high viral load and abnormal liver function with high aflatoxin B1–albumin adduct levels in HIV-positive Ghanaians: preliminary observations

    PubMed Central

    Jolly, P.E.; Shuaib, F.M.; Jiang, Y.; Preko, P.; Baidoo, J.; Stiles, J.K.; Wang, J.-S.; Phillips, T.D.; Williams, J.H.

    2012-01-01

    We examined the association between certain clinical factors and aflatoxin B1–albumin adduct (AF-ALB) levels in HIV-positive people. Plasma samples collected from 314 (155 HIV-positive and 159 HIV-negative) people were tested for AF-ALB levels, viral load, CD4+ T-cell count, liver function profile, malaria parasitaemia, and hepatitis B and C virus infections. HIV-positive participants were divided into high and low groups based on their median AF-ALB of 0.93 pmol mg−1 albumin and multivariable logistic and linear regression methods used to assess relationships between clinical conditions and AF-ALB levels. Multivariable logistic regression showed statistically significant increased odds of having higher HIV viral loads (OR=2.84; 95% CI=1.17–7.78) and higher direct bilirubin levels (OR=5.47; 95% CI=1.03–22.85) among HIV-positive participants in the high AF-ALB group. There were also higher levels of total bilirubin and lower levels of albumin in association with high AF-ALB. Thus, aflatoxin exposure may contribute to high viral loads and abnormal liver function in HIV-positive people and so promote disease progression. PMID:21749228

  4. Association between Serum Bilirubin and Acute Intraoperative Hyperglycemia Induced by Prolonged Intermittent Hepatic Inflow Occlusion in Living Liver Donors

    PubMed Central

    Han, Sangbin; Jin, Sang-Man; Ko, Justin Sangwook; Kim, Young Ri; Gwak, Mi Sook; Son, Hee Jeong; Joh, Jae-Won; Kim, Gaab Soo

    2016-01-01

    Background Intermittent hepatic inflow occlusion (IHIO) is associated with acute hyperglycemia during living donor hepatectomy when the ischemia is prolonged. Bilirubin is a potent antioxidant to play an important role for maintaining insulin sensitivity and preventing hyperglycemia. Thus, we aimed to test whether serum bilirubin level is associated with prolonged IHIO-induced intraoperative hyperglycemia. Methods Seventy-five living liver donors who underwent a prolonged IHIO with a >30 minute cumulative ischemia were included. The association between preoperative serum bilirubin concentrations and the risk of intraoperative hyperglycemia (blood glucose concentration >180 mg/dl) was analyzed using binary logistic regression with adjusting for potential confounders including age and steatosis. Results The number of donors who underwent 3, 4, 5, and 6 rounds of IHIO was 41, 22, 7, and 5, respectively. Twenty-nine (35%) donors developed intraoperative hyperglycemia. Total bilirubin concentration was inversely associated with hyperglycemia risk (odds ratio [OR] 0.033, 95% confidence interval [CI] 0.004–0.313, P = 0.003). There was an interaction between age and total bilirubin concentration: the effect of lower serum total bilirubin (≤0.7 mg/dl) on the development of hyperglycemia was greater in older donors (>40 years) than in younger donors (P = 0.0.028 versus P = 0.212). Both conjugated bilirubin (OR 0.001 95% CI 0.001–0.684) and unconjugated bilirubin (OR 0.011 95% CI 0.001–0.246) showed an independent association with hyperglycemia risk. Conclusions Lower preoperative serum bilirubin was associated with greater risk of prolonged IHIO-induced hyperglycemia during living donor hepatectomy particularly in older donors. Thus, more meticulous glycemic management is recommended when prolonged IHIO is necessary for surgical purposes in old living donors with lower serum bilirubin levels. PMID:27367602

  5. PPARα: A Master Regulator of Bilirubin Homeostasis.

    PubMed

    Bigo, Cyril; Kaeding, Jenny; El Husseini, Diala; Rudkowska, Iwona; Verreault, Mélanie; Vohl, Marie Claude; Barbier, Olivier

    2014-01-01

    Hypolipidemic fibrates activate the peroxisome proliferator-activated receptor (PPAR) α to modulate lipid oxidation and metabolism. The present study aimed at evaluating how 3 PPARα agonists, namely, fenofibrate, gemfibrozil, and Wy14,643, affect bilirubin synthesis and metabolism. Human umbilical vein epithelial cells (HUVEC) and coronary artery smooth muscle cells (CASMC) were cultured in the absence or presence of the 3 activators, and mRNA, protein, and/or activity levels of the bilirubin synthesizing heme oxygenase- (HO-) 1 and biliverdin reductase (BVR) enzymes were determined. Human hepatocytes (HH) and HepG2 cells sustained similar treatments, except that the expression of the bilirubin conjugating UDP-glucuronosyltransferase (UGT) 1A1 enzyme and multidrug resistance-associated protein (MRP) 2 transporter was analyzed. In HUVECs, gemfibrozil, fenofibrate, and Wy14,643 upregulated HO-1 mRNA expression without affecting BVR. Wy14,643 and fenofibrate also caused HO-1 protein accumulation, while gemfibrozil and fenofibrate favored the secretion of bilirubin in cell media. Similar positive regulations were also observed with the 3 PPARα ligands in CASMCs where HO-1 mRNA and protein levels were increased. In HH and HepG2 cells, both UGT1A1 and MRP2 transcripts were also accumulating. These observations indicate that PPARα ligands activate bilirubin synthesis in vascular cells and metabolism in liver cells. The clinical implications of these regulatory events are discussed. PMID:25147562

  6. Initial photochemistry of bilirubin probed by femtosecond spectroscopy.

    PubMed

    Zietz, Burkhard; Gillbro, Tomas

    2007-10-18

    Bilirubin is a breakdown product from heme catabolism, and reduced excretion of bilirubin can lead to jaundice. Phototherapy is the most common treatment for neonatal jaundice, a condition frequently encountered in newborn infants. Knowledge of the photochemistry of bilirubin, which is dominated by (ultra)fast components, is necessary for the profound understanding of the processes in phototherapy. Here, we report results from femtosecond fluorescence upconversion measurements on bilirubin and half-bilirubin model compounds, as well as pump-probe absorption measurements on bilirubin. A fast component of ca. 120 fs in the multiexponential fluorescence decay, being only visible in the bilirubin molecule, is interpreted as exciton localization within the molecular halves. The slower components of several hundreds of femtoseconds and a few picoseconds, occurring in bilirubin and the half-bilirubin model, are interpreted as relaxation to a (twisted) intermediate, which decays further with ca. 15 ps to the ground state. PMID:17927274

  7. Water-soluble adsorbent β-cyclodextrin-grafted polyethyleneimine for removing bilirubin from plasma.

    PubMed

    Wang, Zhi; Wei, Houliang; Jia, Lingyun; Xu, Li; Zou, Chunyi; Xie, Jian

    2012-10-01

    A water-soluble adsorbent was developed for removing bilirubin from the plasma of hyperbilirubinemia patient. The adsorbent was synthesized by grafting β-cyclodextrin (β-CD) to branched polyethyleneimine (PEI) matrix. The resulting β-CD-PEI polymer had an average molecular weight of 163.7 kD, and it contained 56.3 β-CD functional groups. In β-CD-PEI-spiked dialysis, 35.8% of plasma bilirubin was removed, which was higher than that removed by the same concentration of bovine serum albumin. β-CD-PEI also removed aromatic amino acids and bile acids. The results indicated that β-CD-PEI could be an effective adsorbent for blood purification application aiming at the removal of toxins. PMID:22836125

  8. Effect of sodium phenobarbital on bilirubin metabolism in an infant with congenital, nonhemolytic, unconjugated hyperbilirubinemia, and kernicterus

    PubMed Central

    Crigler, John F.; Gold, Norman I.

    1969-01-01

    Sodium phenobarbital and various hormones, compounds capable of hepatic enzyme induction, were given to an infant boy with congenital, nonhemolytic, unconjugated, hyperbilirubinemia and severe kernicterus for prolonged periods between the ages of 2 and 25 months to determine their effect on serum bilirubin concentrations. Phenobarbital, 5 mg/day orally, on two occasions decreased serum bilirubin concentrations approximately threefold over a period of 30 days. Withdrawal of phenobarbital after the first study resulted in a gradual (30 days) return of serum bilirubin to pretreatment levels. The lower serum bilirubin concentrations observed when phenobarbital therapy was reinstituted were maintained for 61 days on 2.5 mg/kg per day of the drug. Orally administered L-triiodothyronine, 0.05-0.1 mg/day for 71 days, intramuscular human growth hormone, 1 mg/day for 21 days, and testosterone propionate, 0.1 mg/day for 9 days, did not decrease serum bilirubin levels below lowest control values of 18 mg/100 ml. Bilirubin-3H was administered twice before and once with bilirubin-14C during phenobarbital therapy to study the kinetics of bilirubin metabolism. Results of the first and second control studies and of the bilirubin-3H and bilirubin-14C phenobarbital studies, respectively, were as follows: total body bilirubin pools, 200, 184, 73, and 72 mg; half-lives, 111, 84, 37, and 39 hr; and turnover, 30, 37, 33, and 31 mg/day. The data show that the approximate threefold decrease in serum bilirubin concentration and total body pool resulted from a comparable decrease in bilirubin half-life without a significant change in turnover. In vitro histological (electron microscopy) and enzymological studies of liver obtained by surgical biopsies before and during phenobaribtal administration showed that both the hepatocyte content of agranular endoplasmic reticulum (AER) and the ability of liver homogenate to conjugate p-nitrophenol were significantly increased during phenobarbital

  9. Bilirubin measured on a blood gas analyser: a suitable alternative for near-patient assessment of neonatal jaundice?

    PubMed

    Peake, M; Mazzachi, B; Fudge, A; Bais, R

    2001-09-01

    The reliability of a recently released total bilirubin assay for a blood gas analyser was assessed in two Australian hospital laboratories. The instrument computes total bilirubin concentration from multi-wavelength absorbance measurements of undiluted whole blood or plasma. Performance of the Radiometer ABL 735 blood gas analyser bilirubin method (software version 3.6) was compared with a proven Roche diazo method for Hitachi analysers, calibrated using primary standards prepared from NIST SRM 916a bilirubin. Acceptable bilirubin results were found over a wide concentration range for most neonatal samples of whole blood or plasma. For adult specimens, bilirubin results were approximately 10% lower on the blood gas analyser. Within-run imprecision (whole blood) was < 2.5%, between-day imprecision (synthetic controls) < 1.0%, and the bilirubin assay for both whole blood and plasma was linear to 1,000 micromol/L. Using sampling options from 35 microL to 195 microL, bilirubin results differed by less than 3%, with a 95 microL syringe option producing the highest results. We conclude that the Radiometer ABL 735 bilirubin assay is suitable for near-patient assessment of neonatal jaundice using whole blood, thus eliminating the need for sample centrifugation. Verification using laboratory methods can be used when required. A positive correction of approximately 10% is required for adult specimens to conform with Hitachi results (SRM 916a calibration), possibly due to the optical characteristics of the higher proportion of conjugated bilirubin and other substances present in most adult samples. PMID:11587132

  10. Bilirubin Levels and Thrombus Burden in Patients With ST-Segment Elevation Myocardial Infarction.

    PubMed

    Hamur, Hikmet; Duman, Hakan; Bakirci, Eftal Murat; Kucuksu, Zafer; Demirelli, Selami; Kalkan, Kamuran; Degirmenci, Husnu

    2016-07-01

    We investigated whether serum bilirubin level (a marker of heme oxygenase activity) is a predictor of thrombus burden in patients with acute myocardial infarction. Patients (n = 229; male 72.9%; mean age 63 ± 13.4 years) who were admitted with ST-segment elevation myocardial infarction (STEMI) were enrolled. Patients were divided into 2 groups. Group 1 was defined as low thrombus burden and group 2 was defined as high thrombus burden. Patients with high thrombus burden had higher total bilirubin levels (14.4 [4.3-22.9] vs 7.7 [2.4-20.3] µmol/L, P ≤ .001), (0.84 [0.25-1.34] vs 0.45 [0.14-1.19] mg/dL P ≤ .001) and direct bilirubin levels (3.1 [2.1-8.4] vs 1.7 [0.5-6.5] µmol/L, P ≤ .001), (0.18 [0.03-0.49] vs 0.10 [0.03-0.38] mg/dL, P ≤ .001). At multivariate analysis, total bilirubin (odds ratio: 1.05, 95% confidence interval: 1.03-1.08, P ≤ .001) was the independent predictor of high thrombus burden. In conclusion, total bilirubin level is independently associated with high thrombus burden in patients with STEMI. PMID:26339042

  11. Alteration of serum bilirubin level in schizophrenia.

    PubMed

    Semnani, Yousef; Nazemi, Farzad; Azariyam, Aileen; Ardakani, Mohammad Javad Ehsani

    2010-11-01

    Abstract Objective. Alteration of serum bilirubin level in acute episodes of psychosis in patients with schizophrenia has been reported but the pattern of this alteration is controversial. Methods. Patients diagnosed as schizophrenia (162, group S) or bipolar disorder (155, group B) entered the study. The control group consisted of 95 patients admitted to cardiac care unit who had no personal or family history of major psychiatric disorders. Pre- and post-admission levels of bilirubin were measured and compared within and between the groups. Patients were examined to exclude all other causes of hyperbilirubinemia. Group S and B participants were also evaluated using positive and negative syndrome subscale (PANSS) both at admission and discharge. Results. The mean admission bilirubin levels of all the groups were in the normal range (significantly higher in group S than groups B and C) and were affected by the score of general psychopathology subscale rather than the scores of positive symptoms subscale. Conclusions. Although bilirubin decreased in all three groups at discharge, the rate of decrease was significantly higher in group S. The reason for this is not clear and needs further study. PMID:24917437

  12. Can Excess Bilirubin Levels Cause Learning Difficulties?

    ERIC Educational Resources Information Center

    Pretorius, E.; Naude, H.; Becker, P. J.

    2002-01-01

    Examined learning problems in South African sample of 7- to 14-year-olds whose mothers reported excessively high infant bilirubin shortly after the child's birth. Found that this sample had lowered verbal ability with the majority also showing impaired short-term and long-term memory. Findings suggested that impaired formation of astrocytes…

  13. Bilirubin is an Endogenous Antioxidant in Human Vascular Endothelial Cells.

    PubMed

    Ziberna, Lovro; Martelanc, Mitja; Franko, Mladen; Passamonti, Sabina

    2016-01-01

    Bilirubin is a standard serum biomarker of liver function. Inexplicably, it is inversely correlated with cardiovascular disease risk. Given the role of endothelial dysfunction in originating cardiovascular diseases, direct analysis of bilirubin in the vascular endothelium would shed light on these relationships. Hence, we used high-performance liquid chromatography coupled with thermal lens spectrometric detection and diode array detection for the determination of endogenous cellular IXα-bilirubin. To confirm the isomer IXα-bilirubin, we used ultra-performance liquid chromatography coupled with a high-resolution mass spectrometer using an electrospray ionization source, as well as tandem mass spectrometric detection. We measured bilirubin in both arterial and venous rat endothelium (0.9-1.5 pmol mg(-1) protein). In the human endothelial Ea.hy926 cell line, we demonstrated that intracellular bilirubin (3-5 pmol mg(-1) protein) could be modulated by either extracellular bilirubin uptake, or by up-regulation of heme oxygenase-1, a cellular enzyme related to endogenous bilirubin synthesis. Moreover, we determined intracellular antioxidant activity by bilirubin, with EC50 = 11.4 ± 0.2 nM, in the range of reported values of free serum bilirubin (8.5-13.1 nM). Biliverdin showed similar antioxidant properties as bilirubin. We infer from these observations that intra-endothelial bilirubin oscillates, and may thus be a dynamic factor of the endothelial function. PMID:27381978

  14. Bilirubin is an Endogenous Antioxidant in Human Vascular Endothelial Cells

    PubMed Central

    Ziberna, Lovro; Martelanc, Mitja; Franko, Mladen; Passamonti, Sabina

    2016-01-01

    Bilirubin is a standard serum biomarker of liver function. Inexplicably, it is inversely correlated with cardiovascular disease risk. Given the role of endothelial dysfunction in originating cardiovascular diseases, direct analysis of bilirubin in the vascular endothelium would shed light on these relationships. Hence, we used high-performance liquid chromatography coupled with thermal lens spectrometric detection and diode array detection for the determination of endogenous cellular IXα-bilirubin. To confirm the isomer IXα-bilirubin, we used ultra-performance liquid chromatography coupled with a high-resolution mass spectrometer using an electrospray ionization source, as well as tandem mass spectrometric detection. We measured bilirubin in both arterial and venous rat endothelium (0.9–1.5 pmol mg−1 protein). In the human endothelial Ea.hy926 cell line, we demonstrated that intracellular bilirubin (3–5 pmol mg−1 protein) could be modulated by either extracellular bilirubin uptake, or by up-regulation of heme oxygenase-1, a cellular enzyme related to endogenous bilirubin synthesis. Moreover, we determined intracellular antioxidant activity by bilirubin, with EC50 = 11.4 ± 0.2 nM, in the range of reported values of free serum bilirubin (8.5–13.1 nM). Biliverdin showed similar antioxidant properties as bilirubin. We infer from these observations that intra-endothelial bilirubin oscillates, and may thus be a dynamic factor of the endothelial function. PMID:27381978

  15. Serum bilirubin value predicts hospital admission in carbon monoxide-poisoned patients. Active player or simple bystander?

    PubMed Central

    Cervellin, Gianfranco; Comelli, Ivan; Buonocore, Ruggero; Picanza, Alessandra; Rastelli, Gianni; Lippi, Giuseppe

    2015-01-01

    OBJECTIVES: Although carbon monoxide poisoning is a major medical emergency, the armamentarium of recognized prognostic biomarkers displays unsatisfactory diagnostic performance for predicting cumulative endpoints. METHODS: We performed a retrospective and observational study to identify all patients admitted for carbon monoxide poisoning during a 2-year period. Complete demographical and clinical information, along with the laboratory data regarding arterial carboxyhemoglobin, hemoglobin, blood lactate and total serum bilirubin, was retrieved. RESULTS: The study population consisted of 38 poisoned patients (23 females and 15 males; mean age 39±21 years). Compared with discharged subjects, hospitalized patients displayed significantly higher values for blood lactate and total serum bilirubin, whereas arterial carboxyhemoglobin and hemoglobin did not differ. In a univariate analysis, hospitalization was significantly associated with blood lactate and total serum bilirubin, but not with age, sex, hemoglobin or carboxyhemoglobin. The diagnostic performance obtained after combining the blood lactate and total serum bilirubin results (area under the curve, 0.90; 95% CI, 0.81-0.99; p<0.001) was better than that obtained for either parameter alone. CONCLUSION: Although it remains unclear whether total serum bilirubin acts as an active player or a bystander, we conclude that the systematic assessment of bilirubin may, alongside lactate levels, provide useful information for clinical decision making regarding carbon monoxide poisoning. PMID:26375565

  16. Human serum albumin and its relation with oxidative stress.

    PubMed

    Sitar, Mustafa Erinç; Aydin, Seval; Cakatay, Ufuk

    2013-01-01

    Human serum albumin, a negative acute phase reactant and marker of nutritive status, presents at high concentrations in plasma. Albumin has always been used in many clinical states especially to improve circulatory failure. It has been showed that albumin is involved in many bioactive functions such as regulation of plasma osmotic pressure, binding and transport of various endogenous or exogenous compounds, and finally extracellular antioxidant defenses. Molecules like transferrin, caeruloplasmin, haptoglobin, uric acid, bilirubin, alpha-tocopherol, glucose, and albumin constitute extracellular antioxidant defenses in blood plasma but albumin is the most potent one. Most of the antioxidant properties of albumin can be attributed to its unique biochemical structure. The protein possesses antioxidant properties such as binding copper tightly and iron weakly, scavenging free radicals, e.g., hypochlorous acid (HOCl) and Peroxynitrite (ONOOH) and providing thiol group (-SH). Whether it is chronic or acute, during many pathological conditions, biomarkers of oxidative protein damage increase and this observation continues with considerable oxidation of human serum albumin. There is an important necessity to specify its interactions with Reactive Oxygen Species. Generally, it may lower the availability of pro-oxidants and be preferentially oxidized to protect other macromolecules but all these findings make it necessary that researchers give a more detailed explanation of albumin and its relations with oxidative stress. PMID:24273915

  17. Bilirubin-Induced Neurotoxicity in the Preterm Neonate.

    PubMed

    Watchko, Jon F

    2016-06-01

    Bilirubin-induced neurotoxicity in preterm neonates remains a clinical concern. Multiple cellular and molecular cascades likely underlie bilirubin-induced neuronal injury, including plasma membrane perturbations, excitotoxicity, neuroinflammation, oxidative stress, and cell cycle arrest. Preterm newborns are particularly vulnerable secondary to central nervous system immaturity and concurrent adverse clinical conditions that may potentiate bilirubin toxicity. Acute bilirubin encephalopathy in preterm neonates may be subtle and manifest primarily as recurrent symptomatic apneic events. Low-bilirubin kernicterus continues to be reported in preterm neonates, and although multifactorial in nature, is often associated with marked hypoalbuminemia. PMID:27235209

  18. Repression of the albumin gene in Novikoff hepatoma cells.

    PubMed Central

    Capetanaki, Y G; Flytzanis, C N; Alonso, A

    1982-01-01

    Novikoff hepatoma cells have lost their capacity to synthesize albumin. As a first approach to study the mechanisms underlying this event, in vitro translation in a reticulocyte system was performed using total polyadenylated mRNA from rat liver and Novikoff hepatoma cells. Immunoprecipitation of the in vitro translation products with albumin-specific antibody revealed a total lack of albumin synthesis in Novikoff hepatoma, suggesting the absence of functional albumin mRNA in these cells. Titration experiments using as probe albumin cDNA cloned in pBR322 plasmid demonstrated the absence of albumin-specific sequences in both polysomal and nuclear polyadenylated and total RNA from Novikoff cells. This albumin recombinant plasmid was obtained by screening a rat liver cDNA library with albumin [32P]cDNA reverse transcribed from immuno-precipitated mRNA. The presence of an albumin-specific gene insert was documented with translation assays as well as by restriction mapping. Repression of the albumin gene at the transcriptional level was further demonstrated by RNA blotting experiments using the cloned albumin cDNA probe. Genomic DNA blots using the cloned albumin cDNA as probe did not reveal any large-scale deletions, insertions, or rearrangements in the albumin gene, suggesting that the processes involved in the suppression of albumin mRNA synthesis do not involve extensive genomic rearrangements. Images PMID:6180302

  19. Regression approach to non-invasive determination of bilirubin in neonatal blood

    NASA Astrophysics Data System (ADS)

    Lysenko, S. A.; Kugeiko, M. M.

    2012-07-01

    A statistical ensemble of structural and biophysical parameters of neonatal skin was modeled based on experimental data. Diffuse scattering coefficients of the skin in the visible and infrared regions were calculated by applying a Monte-Carlo method to each realization of the ensemble. The potential accuracy of recovering the bilirubin concentration in dermis (which correlates closely with that in blood) was estimated from spatially resolved spectrometric measurements of diffuse scattering. The possibility to determine noninvasively the bilirubin concentration was shown by measurements of diffuse scattering at λ = 460, 500, and 660 nm at three source-detector separations under conditions of total variability of the skin biophysical parameters.

  20. Smoking Cessation Is Followed by Increases in Serum Bilirubin, an Endogenous Antioxidant Associated With Lower Risk of Lung Cancer and Cardiovascular Disease

    PubMed Central

    Wu, Ran; Mayne, Susan T.; Jatlow, Peter I.

    2014-01-01

    Introduction: Lower concentrations of serum bilirubin, an endogenous antioxidant, have been associated with risk of many smoking-related diseases, including lung cancer and cardiovascular disease, and current smokers are reported to have lower bilirubin levels than nonsmokers and past smokers. This study evaluates the effects of smoking cessation on bilirubin levels. Methods: In a secondary analysis of a 6-week placebo-controlled trial of naltrexone for smoking cessation, indirect and total bilirubin concentrations were evaluated at baseline and following smoking cessation. Individuals who were continuously abstinent for 6 weeks (n = 155) were compared to those who were not (n = 193). Participants reported smoking ≥20 cigarettes daily at baseline and received smoking cessation counseling, 21mg nicotine patch daily, and either placebo or 1 of 3 doses of naltrexone (25, 50, or 100mg) for 6 weeks. Change in indirect and total bilirubin following the quit date was measured at Weeks 1, 4, and 6 compared to baseline. Results: Individuals who were continuously abstinent from smoking, independent of naltrexone condition, showed a significantly greater mean increase in indirect (~unconjugated) bilirubin (0.06mg/dl, SD = 0.165) compared to those who did not (mean = 0.02, SD = 0.148, p = .015). Similar results were obtained for total bilirubin (p = .037). Conclusions: Smoking cessation is followed by increases in bilirubin concentration that have been associated with lower risk of lung cancer and cardiovascular disease. PMID:24812024

  1. Hepatocyte cotransport of taurocholate and bilirubin glucuronides: Role of microtubules

    SciTech Connect

    Crawford, J.M.; Gollan, J.L. )

    1988-07-01

    Modulation of bile pigment excretion by bile salts has been attributed to modification of canalicular membrane transport or a physical interaction in bile. Based on the observation that a microtubule-dependent pathway is involved in the hepatocellular transport of bile salts, the authors investigated the possibility that bilirubin glucuronides are associated with bile salts during intracellular transport. Experiments were conducted in intact rats (basal) or after overnight biliary diversion and intravenous reinfusion of taurocholate (depleted/reinfused). All rats were pretreated with intravenous low-dose colchicine or its inactive isomer lumicolchicine. Biliary excretion of radiolabeled bilirubin glucuronides derived from tracer ({sup 14}C)bilirubin-({sup 3}H)bilirubin monoglucuronide (coinjected iv) was unchanged in basal rats but was consistently delayed in depleted/reinfused rats. This was accompanied by a significant shift toward bilirubin diglucuronide formation from both substrates. In basal Gunn rats, with deficient bilirubin glucuronidation, biliary excretion of intravenous ({sup 14}C)bilirubin monoglucuronide-({sup 3}H)bilirubin diglucuronide was unaffected by colchicine but was retarded in depleted/reinfused Gunn rats. Colchicine had no effect on the rate of bilirubin glucuronidation in vitro in rat liver microsomes. They conclude that a portion of the bilirubin glucuronides generated endogenously in hepatocytes or taken up directly from plasma may be cotransported with bile salts to the bile canalicular membrane via a microtubule-dependent mechanism.

  2. Albumin and multiple sclerosis.

    PubMed

    LeVine, Steven M

    2016-01-01

    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. PMID:27067000

  3. Evidence for covalent binding of acyl glucuronides to serum albumin via an imine mechanism as revealed by tandem mass spectrometry.

    PubMed Central

    Ding, A; Ojingwa, J C; McDonagh, A F; Burlingame, A L; Benet, L Z

    1993-01-01

    Acyl glucuronide metabolites of bilirubin and many drugs can react with serum albumin in vivo to form covalent adducts. Such adducts may be responsible for some toxic effects of carboxylic nonsteroidal antiinflammatory agents. The mechanism of formation of the adducts and their chemical structures are unknown. In this paper we describe the use of tandem mass spectrometry to locate binding sites and elucidate the binding mechanism involved in the formation of covalent adducts from tolmetin glucuronide and albumin in vitro. Human serum albumin and excess tolmetin glucuronide were coincubated in the presence of sodium cyanoborohydride to trap imine intermediates. The total protein product was reduced, carboxymethylated, and digested with trypsin. Six tolmetin-containing peptides (indicated by absorbance at 313 nm) were isolated by high-pressure liquid chromatography and analyzed by liquid secondary-ion mass spectrometry and collision-induced dissociation, using a four-sector tandem mass spectrometer. All six peptides contained tolmetin linked covalently via a glucuronic acid to protein lysine groups. Major attachment sites on the protein were Lys-195, -199, and -525; minor sites were identified as Lys-137, -351, and -541. Our results show unambiguously that the glucuronic acid moiety of acyl glucuronides can be retained within the structure when these reactive metabolites bind covalently to proteins, and they suggest that acyl migration followed by Schiff base (imine) formation is a credible mechanism for the generation of covalent adducts in vivo. PMID:8483897

  4. Albumin - blood (serum) test

    MedlinePlus

    ... nutrients, such as with: After weight-loss surgery Crohn disease Low-protein diets Celiac disease Whipple disease Increased ... Bilirubin blood test Burns Celiac disease - sprue Cirrhosis Crohn disease Diabetes and kidney disease Glomerulonephritis Hepatitis Hepatorenal syndrome ...

  5. Serum Bilirubin Is Inversely Associated with Increased Arterial Stiffness in Men with Pre-Hypertension but Not Normotension

    PubMed Central

    Huang, Yao-Hsien; Yang, Yi-Ching; Lu, Feng-Hwa; Sun, Zih-Jie; Wu, Jin-Shang; Chang, Chih-Jen

    2016-01-01

    Objective Serum bilirubin level has shown to be inversely associated with coronary atherosclerosis, and may serve as a protective biomarker of coronary artery disease. Serum bilirubin has also been shown to be negatively associated with brachial-ankle pulse wave velocity (baPWV) in men without a history of hypertension, and in men with hypertension. It is unknown whether such associations can be observed in the pre-hypertensive or normotensive population. This study thus aimed to investigate the relationship between serum bilirubin level and increased arterial stiffness in subjects with pre-hypertension and normotension for both genders. Methods A cross-sectional sample of 3,399 apparently healthy subjects undergoing a medical check-up at National Cheng Kung University Hospital was enrolled between October 2006 and August 2009, after excluding subjects with serum total bilirubin level greater than 20.52 μmol/L. Increased arterial stiffness was defined as baPWV of 1,400 cm/s or higher as the dichotomous variable and bilirubin as the continuous variable. Results Based on multiple linear regression analysis, serum bilirubin level was inversely associated with baPWV in non-hypertensive men (β = -0.066, p < 0.001) but not in non-hypertensive women. In addition, the inverse relationship between bilirubin level and baPWV was found statistically significant only in pre-hypertensive men (β = -0.110, p < 0.001). Multiple logistic regression analysis showed that serum bilirubin was inversely associated with increased arterial stiffness in men with pre-hypertension (odds ratio = 0.955, 95% confidence interval = 0.916–0.996, p < 0.05) but not normotension after adjustment for other confounding factors. However, the relationship between total bilirubin level and increased arterial stiffness did not reach statistical significance for female subjects with pre-hypertension and normotension. Conclusion Serum bilirubin is inversely associated with increased arterial stiffness in

  6. Preliminary development of a fiber optic sensor for measuring bilirubin.

    PubMed

    Babin, Steven M; Sova, Raymond M

    2014-01-01

    Preliminary development of a fiber optic bilirubin sensor is described, where an unclad sensing portion is used to provide evanescent wave interaction of the transmitted light with the chemical environment. By using a wavelength corresponding to a bilirubin absorption peak, the Beer-Lambert Law can be used to relate the concentration of bilirubin surrounding the sensing portion to the amount of absorbed light. Initial testing in vitro suggests that the sensor response is consistent with the results of bulk absorption measurements as well as the Beer-Lambert Law. In addition, it is found that conjugated and unconjugated bilirubin have different peak absorption wavelengths, so that two optical frequencies may potentially be used to measure both types of bilirubin. Future development of this device could provide a means of real-time, point-of-care monitoring of intravenous bilirubin in critical care neonates with hyperbilirubinemia. PMID:25057239

  7. Preliminary Development of a Fiber Optic Sensor for Measuring Bilirubin

    PubMed Central

    Babin, Steven M; Sova, Raymond M

    2014-01-01

    Preliminary development of a fiber optic bilirubin sensor is described, where an unclad sensing portion is used to provide evanescent wave interaction of the transmitted light with the chemical environment. By using a wavelength corresponding to a bilirubin absorption peak, the Beer–Lambert Law can be used to relate the concentration of bilirubin surrounding the sensing portion to the amount of absorbed light. Initial testing in vitro suggests that the sensor response is consistent with the results of bulk absorption measurements as well as the Beer–Lambert Law. In addition, it is found that conjugated and unconjugated bilirubin have different peak absorption wavelengths, so that two optical frequencies may potentially be used to measure both types of bilirubin. Future development of this device could provide a means of real-time, point-of-care monitoring of intravenous bilirubin in critical care neonates with hyperbilirubinemia. PMID:25057239

  8. Human podocytes perform polarized, caveolae-dependent albumin endocytosis

    PubMed Central

    Dobrinskikh, Evgenia; Okamura, Kayo; Kopp, Jeffrey B.; Doctor, R. Brian

    2014-01-01

    The renal glomerulus forms a selective filtration barrier that allows the passage of water, ions, and small solutes into the urinary space while restricting the passage of cells and macromolecules. The three layers of the glomerular filtration barrier include the vascular endothelium, glomerular basement membrane (GBM), and podocyte epithelium. Podocytes are capable of internalizing albumin and are hypothesized to clear proteins that traverse the GBM. The present study followed the fate of FITC-labeled albumin to establish the mechanisms of albumin endocytosis and processing by podocytes. Confocal imaging and total internal reflection fluorescence microscopy of immortalized human podocytes showed FITC-albumin endocytosis occurred preferentially across the basal membrane. Inhibition of clathrin-mediated endocytosis and caveolae-mediated endocytosis demonstrated that the majority of FITC-albumin entered podocytes through caveolae. Once internalized, FITC-albumin colocalized with EEA1 and LAMP1, endocytic markers, and with the neonatal Fc receptor, a marker for transcytosis. After preloading podocytes with FITC-albumin, the majority of loaded FITC-albumin was lost over the subsequent 60 min of incubation. A portion of the loss of albumin occurred via lysosomal degradation as pretreatment with leupeptin, a lysosomal protease inhibitor, partially inhibited the loss of FITC-albumin. Consistent with transcytosis of albumin, preloaded podocytes also progressively released FITC-albumin into the extracellular media. These studies confirm the ability of podocytes to endocytose albumin and provide mechanistic insight into cellular mechanisms and fates of albumin handling in podocytes. PMID:24573386

  9. Bilirubin and its oxidation products damage brain white matter.

    PubMed

    Lakovic, Katarina; Ai, Jinglu; D'Abbondanza, Josephine; Tariq, Asma; Sabri, Mohammed; Alarfaj, Abdullah K; Vasdev, Punarjot; Macdonald, Robert Loch

    2014-11-01

    Brain injury after intracerebral hemorrhage (ICH) occurs in cortex and white matter and may be mediated by blood breakdown products, including hemoglobin and heme. Effects of blood breakdown products, bilirubin and bilirubin oxidation products, have not been widely investigated in adult brain. Here, we first determined the effect of bilirubin and its oxidation products on the structure and function of white matter in vitro using brain slices. Subsequently, we determined whether these compounds have an effect on the structure and function of white matter in vivo. In all, 0.5 mmol/L bilirubin treatment significantly damaged both the function and the structure of myelinated axons but not the unmyelinated axons in brain slices. Toxicity of bilirubin in vitro was prevented by dimethyl sulfoxide. Bilirubin oxidation products (BOXes) may be responsible for the toxicity of bilirubin. In in vivo experiments, unmyelinated axons were found more susceptible to damage from bilirubin injection. These results suggest that unmyelinated axons may have a major role in white-matter damage in vivo. Since bilirubin and BOXes appear in a delayed manner after ICH, preventing their toxic effects may be worth investigating therapeutically. Dimethyl sulfoxide or its structurally related derivatives may have a potential therapeutic value at antagonizing axonal damage after hemorrhagic stroke. PMID:25160671

  10. Bilirubin and its oxidation products damage brain white matter

    PubMed Central

    Lakovic, Katarina; Ai, Jinglu; D'Abbondanza, Josephine; Tariq, Asma; Sabri, Mohammed; Alarfaj, Abdullah K; Vasdev, Punarjot; Macdonald, Robert Loch

    2014-01-01

    Brain injury after intracerebral hemorrhage (ICH) occurs in cortex and white matter and may be mediated by blood breakdown products, including hemoglobin and heme. Effects of blood breakdown products, bilirubin and bilirubin oxidation products, have not been widely investigated in adult brain. Here, we first determined the effect of bilirubin and its oxidation products on the structure and function of white matter in vitro using brain slices. Subsequently, we determined whether these compounds have an effect on the structure and function of white matter in vivo. In all, 0.5 mmol/L bilirubin treatment significantly damaged both the function and the structure of myelinated axons but not the unmyelinated axons in brain slices. Toxicity of bilirubin in vitro was prevented by dimethyl sulfoxide. Bilirubin oxidation products (BOXes) may be responsible for the toxicity of bilirubin. In in vivo experiments, unmyelinated axons were found more susceptible to damage from bilirubin injection. These results suggest that unmyelinated axons may have a major role in white-matter damage in vivo. Since bilirubin and BOXes appear in a delayed manner after ICH, preventing their toxic effects may be worth investigating therapeutically. Dimethyl sulfoxide or its structurally related derivatives may have a potential therapeutic value at antagonizing axonal damage after hemorrhagic stroke. PMID:25160671

  11. [Quantifying intestino-esophageal reflux with a fiberoptic bilirubin detection probe].

    PubMed

    Stein, H J; Kraemer, S J; Feussner, H; Siewert, J R

    1994-05-01

    Currently available methods to assess reflux of duodenal contents into the esophagus are cumbersome, unphysiologic, and inaccurate. The role of intestino-esophageal reflux has therefore been controversial. We assessed intestino-esophageal reflux using a new system which allows prolonged intraesophageal measurement of bilirubin, the major pigment of bile. Measurements were made with a newly developed fiber-optic sensor electrode connected to a portable data processing unit (BILITEC 2000, Synectics Medical Inc., Sweden). Light absorption was measured at the absorption peak of bilirubin and a reference point. Studies were performed in 9 subjects without esophagitis, 9 subjects with esophagitis and primary reflux disease and 7 subjects with erosive esophagitis after a total or subtotal gastrectomy. The fiberoptic electrode was placed 5 cm above the lower esophageal sphincter. In vitro studies showed linear correlations between absorbance measurements obtained with the BILITEC-unit and known bilirubin and bile acid concentrations, respectively (p < 0.01). Compared to both other groups, light absorption was markedly increased in the subjects who had esophagitis after a total or subtotal gastrectomy (p < 0.05) indicating severe biliary reflux. An increase in bilirubin absorption occurred particularly during the post-prandial and supine periodes (p < 0.01). A Roux-en-Y biliary diversion procedure completely abolished bile reflux in 2 of these patients. These data indicate that ambulatory 24-hour fiberoptic measurement of bilirubin in the esophagus is feasible and allows quantitation of intestino-esophageal reflux. Intestino-esophageal reflux occurs particularly during the postprandial period and the early morning hours in patients who had a previous subtotal or total gastrectomy. PMID:8073796

  12. Functionalized Magnetic Fe3O4-β-Cyclodextran Nanoparticles for Efficient Removal of Bilirubin.

    PubMed

    Han, Lulu; Chu, Simin; Wei, Houliang; Ren, Jun; Xu, Li; Jia, Lingyun

    2016-06-01

    Bilirubin (BR), as a lipophilic toxin, can binds and deposits in various tissues, especially the brain tissue, leading to hepatic coma and even death. Magnetic nanoparticles adsorbent modified by β-cyclodextran (Fe3O4-β-CD) was developed to remove the BR from the plasma. Fe3O4-β-CD nanoparticles was prepared through Schiff base reaction between the polyethylenimine (PEI)-modified Fe3O4 and aldehyde-functionalized β-CD, and characterized by Fourier transform infrared (FTIR) spectra, X-ray diffraction (XRD), transmission electron microscopy (TEM), vibrating sample magnetometer (VSM) and dynamic light scattering (DLS). Under optimized conditions, the Fe3O4-β-CD adsorbent could adsorb 225.6 mg/g free BR in PBS and reach the adsorption equilibrium within 90 min mainly through hydrophobic interaction; Moreover, the adsorbent displayed better adsorption capability in a dialysis system for BSA-bound bilirubin, plasma bilirubin and total bile acid, and the removal rates of those were 66%, 31% and 41% respectively. Because of the advantages of fast separation and purification process, low preparation cost, good adsorption capability for plasma bilirubin, Fe3O4-β-CD may become an economical and promising absorbent of BR for clinical applications. PMID:27427594

  13. INDUCTION OF BILIRUBIN CLEARANCE BY THE CONSTITUTIVE ANDROSTANE RECEPTOR (CAR)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bilirubin clearance is one of the numerous important functions of the liver. Defects in this process result in jaundice, which is particularly common in neonates. Elevated bilirubin levels can be decreased by treatment with phenobarbital. Because the nuclear hormone receptor constitutive androstane ...

  14. Conjugated Bilirubin Triggers Anemia by Inducing Erythrocyte Death

    PubMed Central

    Lang, Elisabeth; Gatidis, Sergios; Freise, Noemi F; Bock, Hans; Kubitz, Ralf; Lauermann, Christian; Orth, Hans Martin; Klindt, Caroline; Schuier, Maximilian; Keitel, Verena; Reich, Maria; Liu, Guilai; Schmidt, Sebastian; Xu, Haifeng C; Qadri, Syed M; Herebian, Diran; Pandyra, Aleksandra A; Mayatepek, Ertan; Gulbins, Erich; Lang, Florian; Häussinger, Dieter; Lang, Karl S; Föller, Michael; Lang, Philipp A

    2015-01-01

    Hepatic failure is commonly associated with anemia, which may result from gastrointestinal bleeding, vitamin deficiency, or liver-damaging diseases, such as infection and alcohol intoxication. At least in theory, anemia during hepatic failure may result from accelerated clearance of circulating erythrocytes. Here we show that bile duct ligation (BDL) in mice leads to severe anemia despite increased reticulocyte numbers. Bilirubin stimulated suicidal death of human erythrocytes. Mechanistically, bilirubin triggered rapid Ca2+ influx, sphingomyelinase activation, formation of ceramide, and subsequent translocation of phosphatidylserine to the erythrocyte surface. Consistent with our in vitro and in vivo findings, incubation of erythrocytes in serum from patients with liver disease induced suicidal death of erythrocytes in relation to their plasma bilirubin concentration. Consistently, patients with hyperbilirubinemia had significantly lower erythrocyte and significantly higher reticulocyte counts compared to patients with low bilirubin levels. Conclusion: Bilirubin triggers suicidal erythrocyte death, thus contributing to anemia during liver disease. (Hepatology 2015;61:275–284) PMID:25065608

  15. Bilirubin Nanoparticles as a Nanomedicine for Anti-inflammation Therapy.

    PubMed

    Lee, Yonghyun; Kim, Hyungjun; Kang, Sukmo; Lee, Jinju; Park, Jinho; Jon, Sangyong

    2016-06-20

    Despite the high potency of bilirubin as an endogenous anti-inflammatory compound, its clinical translation has been hampered because of its insolubility in water. Bilirubin-based nanoparticles that may overcome this critical issue are presented. A polyethylene glycol compound (PEG) was covalently attached to bilirubin, yielding PEGylated bilirubin (PEG-BR). The PEG-BR self-assembled into nanoscale particles with a size of approximately 110 nm, termed bilirubin nanoparticles (BRNPs). BRNPs are highly efficient hydrogen peroxide scavengers, thereby protecting cells from H2 O2 -induced cytotoxicity. In a murine model of ulcerative colitis, intravenous injection of BRNPs showed preferential accumulation of nanoparticles at the sites of inflammation and significantly inhibited the progression of acute inflammation in the colon. Taken together, BRNPs show potential for use as a therapeutic nanomedicine in various inflammatory diseases. PMID:27144463

  16. In Cellulo Mapping of Subcellular Localized Bilirubin.

    PubMed

    Park, Jong-Seok; Nam, Eunju; Lee, Hye-Kyeong; Lim, Mi Hee; Rhee, Hyun-Woo

    2016-08-19

    Bilirubin (BR) is a de novo synthesized metabolite of human cells. However, subcellular localization of BR in the different organelles of human cells has been largely unknown. Here, utilizing UnaG as a genetically encoded fluorescent BR sensor, we report the existence of relatively BR-enriched and BR-depleted microspaces in various cellular organelles of live cells. Our studies indicate that (i) the cytoplasmic facing membrane of the endoplasmic reticulum (ER) and the nucleus are relatively BR-enriched spaces and (ii) mitochondrial intermembrane space and the ER lumen are relatively BR-depleted spaces. Thus, we demonstrate a relationship between such asymmetrical BR distribution in the ER membrane and the BR metabolic pathway. Furthermore, our results suggest plausible BR-transport and BR-regulating machineries in other cellular compartments, including the nucleus and mitochondria. PMID:27232847

  17. Trans-Cutaneous Bilirubinometery versus Serum Bilirubin in Neonatal Jaundice.

    PubMed

    Mahram, Manoochehr; Oveisi, Sonia; Jaberi, Najmeh

    2015-12-01

    Hyperbilirubinemia is a common problem in neonates and causes serious complications. Thus, serial measurements of bilirubin should be done. This assessment is done through two methods of laboratory measurement in serum sample and transcutaneous bilirubinometer. This descriptive study compared transcutaneous bilirubin assessment and laboratory serum bilirubin. Bilirubin level was assessed among 256 neonates admitted to the Qods Children's Hospital in Qazvin- Iran, because of neonatal indirect jaundice, through two methods of transcutaneous bilirubinometery from two sites of forehead and sternum and laboratory measurement of bilirubin in serum. The cases were non-hemolytic icteric term neonates weighing 2500 gram or more and had not received phototherapy or other treatments. Neonates with hemolytic forms of jaundice, sepsis and suspicious to metabolic disorders were excluded. Assessments by means of KJ-8000 transcutaneous bilirubinometer from two sites of forehead and sternum and through laboratory measurement of serum bilirubin were registered and analyzed. The results of the current study showed that there was a correlation of 0.82 between serum bilirubin and transcutaneous forehead bilirubin assessment and for the used device sensitivity of 0.844; specificity of 0.842, Youden Index of 0.709 and Shortest of 0.042 for a cut-off of 12.4 in bilirubin of participants. Furthermore, Likelihood Ratio positive and negative (LR) were 5.665 and 0.164, respectively and diagnostic Odds Ratio (LR+/LR-) was 34.56. Transcutaneous bilirubinometery can be considered as a reliable tool to assess bilirubin for the screening of neonatal jaundice in term neonates. PMID:26749233

  18. Rapid LC-TOFMS method for identification of binding sites of covalent acylglucuronide-albumin complexes.

    PubMed

    Ohkawa, T; Norikura, R; Yoshikawa, T

    2003-04-10

    A method for rapid identification of binding sites of covalent adducts was developed using delta bilirubin as a model compound. Delta bilirubin, containing intact human serum albumin (HSA), was digested with trypsin and the peptide fragments were monitored at 436 nm, but no predominant peaks were detected indicating the instability of the digested peptides containing bilirubin-related compounds. Therefore, the high-performance liquid chromatography time-of-flight mass spectrometer (LC-TOFMS) data of digested fragments of delta bilirubin were compared with those of control digests of HSA, revealing a characteristic peptide in the digest mixture of delta bilirubin. This peptide was sequenced by high-performance liquid chromatography time-of-flight tandem mass spectrometry (LC-TOFMS/MS) and identified as LDELRDEGKASSAK (Leu182 to Lys195) with a modification of a 178 Da increase at Lys190. This indicated the Lys190 to be a predominant covalent binding site of BGs on HSA via the imine mechanism and the binding between the bilirubin moiety and the glucuronic acid moiety to be unstable to digestion with trypsin. The method of comparing LC-TOFMS data requires no specific detection such as fluorescence or radioactivity for every compound. This should accelerate the structure elucidation of covalent adducts and be helpful for studying the relationship between the structure of ligands and specific binding sites. PMID:12667932

  19. Early postoperative albumin level following total knee arthroplasty is associated with acute kidney injury: A retrospective analysis of 1309 consecutive patients based on kidney disease improving global outcomes criteria.

    PubMed

    Kim, Ha-Jung; Koh, Won-Uk; Kim, Sae-Gyeol; Park, Hyeok-Seong; Song, Jun-Gol; Ro, Young-Jin; Yang, Hong-Seuk

    2016-08-01

    Hypoalbuminemia has been reported to be an independent risk factor for acute kidney injury (AKI). However, little is known about the relationship between the albumin level and the incidence of AKI in patients undergoing total knee arthroplasty (TKA). The aim of our study was to assess incidence and risk factors for AKI and to evaluate the relationship between albumin level and AKI following TKA.The study included a retrospective review of medical records of 1309 consecutive patients who underwent TKA between January 2008 and December 2014. The patients were divided into 2 groups according to the lowest serum albumin level within 2 postoperative days (POD2_alb level < 3.0 g/dL vs ≥3.0 g/dL). Multivariate logistic regression analysis was used to assess risk factors for AKI. A comparison of incidence of AKI, hospital stay, and overall mortality in the 2 groups was performed using propensity score analysis.Of 1309 patients, 57 (4.4%) developed AKI based on Kidney Disease Improving Global Outcomes criteria. Factors associated with AKI included age (odds ratio [OR] 1.05; 95% confidence interval [CI] 1.01-1.09; P = 0.030), diabetes (OR 3.12; 95% CI 1.65-5.89; P < 0.001), uric acid (OR 1.51; 95% CI 1.26-1.82; P < 0.001), beta blocker use (OR 2.65; 95% CI 1.48-4.73; P = 0.001), diuretics (OR 16.42; 95% CI 3.08-87.68; P = 0.001), and POD2_alb level < 3.0 g/dL (OR 1.92; 95% CI 1.09-3.37; P = 0.023). After propensity score analysis, POD2_alb level<3.0 g/dL was associated with AKI occurrence (OR 1.82; 95% CI 1.03-3.24, P = 0.041) and longer hospital stay (P = 0.001).In this study, we demonstrated that POD2_alb level<3.0 g/dL was an independent risk factor for AKI and lengthened hospital stay in patients undergoing TKA. PMID:27495094

  20. Effects of branched-chain amino acid granules on serum albumin level and prognosis are dependent on treatment adherence in patients with liver cirrhosis

    PubMed Central

    Takaguchi, Koichi; Moriwaki, Hisataka; Doyama, Hisashi; Iida, Masayuki; Yagura, Michiyasu; Shimada, Noritomo; Kang, Masahiro; Yamada, Haruki; Kumada, Hiromitsu

    2013-01-01

    Aim To test if the treatment adherence to branched-chain amino acid (BCAA) granules influences the serum albumin level and prognosis in prospective 2984 patients with decompensated liver cirrhosis who were prescribed BCAA granules containing 952 mg of L-isoleucine, 1904 mg of L-leucine and 1144 mg of L-valine at 4.15 g/sachet three times a day after meals. Methods The primary end-point was the time to the event defined as “hospital admission due to progression of hepatic failure”, and factors affecting this outcome were explored. Changes in serum albumin level were evaluated as the secondary end-point. Results Patients were divided into the good adherence group (those who reported to have taken “nearly all” prescribed doses) and the poor adherence group (those who reported to have taken “approximately half” or “less” doses), because such stratification was validated by treatment responses in plasma BCAA/tyrosine ratio. Factors related to the primary end-point were age, drug adherence during 6 months of study treatment, previous hepatic cancer, current clinical manifestations, previous clinical manifestations, baseline serum albumin level, platelet count and total bilirubin level. The cumulative event-free survival was significantly higher in the good adherence group. Increase in the serum albumin level was also greater in the good adherence group. Conclusion Higher BCAA treatment adherence better raised the serum albumin level, leading to improvement of event-free survival. These results indicate the importance of patient instruction for the adequate use of BCAA granules. PMID:23046471

  1. Bilirubin as an endogenous modulator of neurotrophin redox signaling.

    PubMed

    Mancuso, Cesare; Capone, Caterina; Ranieri, Sofia Chiatamone; Fusco, Salvatore; Calabrese, Vittorio; Eboli, Maria Luisa; Preziosi, Paolo; Galeotti, Tommaso; Pani, Giovambattista

    2008-08-01

    Bilirubin is neurotoxic upon excess accumulation in the brain, but it also plays important physiological roles related to its antioxidant properties. Here we report that exposure of PC12 and primary rat cerebellar granule neurons to bilirubin (0.5-10 microM) drastically decreases nerve growth factor (NGF)/brain-derived neurotrophic factor signaling to Akt and extracellular signal-regulated kinases (ERKs), indicating a direct interference of the molecule with crucial prosurvival signaling pathways. This effect likely involves the scavenging capacity of bilirubin, the latter being able to inhibit, in PC12 cells, accumulation of intracellular reactive oxygen species and phosphorylation of Akt and ERKs in response to extracellular hydrogen peroxide. Interestingly, in the absence of exogenous growth factor, bilirubin elicited the phosphorylation of ERKs and of the cAMP responsive element binding (CREB) transcription factor, a signature of NGF-dependent survival signaling. These growth factor-like signaling effects were paralleled by the induction of the neuronal nitric oxide synthase (nNOS) and generation of nitric oxide (NO). Pharmacological dissection of the signaling cascade triggered by bilirubin revealed that phosphorylation of ERKs requires NO signaling through soluble guanylyl cyclase, and, further upstream, influx of extracellular calcium is necessary for nNOS induction and NO release, likely through calcium-dependent phosphorylation of CREB. Importantly, the cascade elicited by bilirubin through NO and ERK is cytoprotective, as revealed by exacerbated bilirubin toxicity in cultures treated by either NOS or MEK inhibitors. Taken together, these observations indicate an important action of bilirubin on redox signaling by neurotrophins, with either inhibitory or agonistic effects based on growth factor availability. PMID:18338802

  2. Longitudinal Blood Pressure Control, Long-Term Mortality, and Predictive Utility of Serum Liver Enzymes and Bilirubin in Hypertensive Patients.

    PubMed

    McCallum, Linsay; Panniyammakal, Jeemon; Hastie, Claire E; Hewitt, Jonathan; Patel, Rajan; Jones, Gregory C; Muir, Scott; Walters, Matthew; Sattar, Naveed; Dominiczak, Anna F; Padmanabhan, Sandosh

    2015-07-01

    There is accruing evidence from general population studies that serum bilirubin and liver enzymes affect blood pressure (BP) and cardiovascular risk, but it is unclear whether these have an impact on hypertensive patients in terms of long-term survival or BP control. We analyzed 12 000 treated hypertensive individuals attending a tertiary care clinic followed up for 35 years for association between baseline liver function tests and cause-specific mortality after adjustment for conventional cardiovascular covariates. Generalized estimating equations were used to study the association of liver tests and follow-up BP. The total time at risk was 173 806 person years with median survival 32.3 years. Follow-up systolic BP over 5 years changed by -0.4 (alanine transaminase and bilirubin), +2.1(alkaline phosphatase), +0.9(γ-glutamyl transpeptidase) mm Hg for each standard deviation increase. Serum total bilirubin and alanine transaminase showed a significant negative association with all-cause and cardiovascular mortality, whereas alkaline phosphatase and γ-glutamyl transpeptidase showed a positive association and aspartate transaminase showed a U-shapedassociation. Serum bilirubin showed an incremental improvement of continuous net reclassification improvement by 8% to 26% for 25 year and 35 year cardiovascular mortality, whereas all liver markers together improved continuous net reclassification improvement by 19% to 47% compared with reference model. In hypertensive patients, serum liver enzymes and bilirubin within 4 standard deviations of the mean show independent effects on mortality and BP control. Our findings would support further studies to elucidate the mechanisms by which liver enzymes and bilirubin may exert an effect on BP and cardiovascular risk, but there is little support for using them in risk stratification. PMID:25941342

  3. Hepatic Conversion of Bilirubin Monoglucuronide to Diglucuronide in Uridine Diphosphate-Glucuronyl Transferase-Deficient Man and Rat by Bilirubin Glucuronoside Glucuronosyltransferase

    PubMed Central

    Chowdhury, J. Roy; Jansen, P. L. M.; Fischberg, E. B.; Daniller, A.; Arias, I. M.

    1978-01-01

    The microsomal enzyme uridine diphosphate (UDP) glucuronate glucuronyltransferase (E.C. 2.4.1.17) catalyzes formation of bilirubin mono-glucuronide from bilirubin and UDPglucuronic acid. Bilirubin glucuronoside glucuronosyltransferase (E.C. 2.4.1.95), an enzyme concentrated in plasma membrane-enriched fractions of rat liver, converts bilirubin monoglucuronide to bilirubin diglucuronide. Bilirubin glucuronoside glucuronosyltransferase activity was studied in homogenates of liver biopsy specimens obtained from patients with the Crigler-Najjar syndrome (Type I) and in subcellular liver fractions of rats homozygous for UDP glucuronate glucuronyltransferase deficiency (Gunn strain). In patients with the Crigler-Najjar syndrome (Type I) and in Gunn rats, hepatic UDPglucuronate glucuronyltransferase activity was not measurable; however, bilirubin glucuronoside glucuronosyltransferase activity was similar to that in normal controls. The subcellular distribution of bilirubin glucuronoside glucuronosyltransferase activity in Gunn rat liver was similar to the distribution observed in normal Wistar rat liver. When bilirubin monoglucuronide was infused intravenously into Gunn rats, 29±5% of the conjugated bilirubin excreted in bile was bilirubin diglucuronide. After transplantation of normal Wistar rat kidney, which contained UDPglucuronate glucuronyltransferase activity, in Gunn rats, the serum bilirubin concentration decreased by 80% in 4 days. The major route of bilirubin removal was biliary excretion of conjugated bilirubin, approximately 70% of which was bilirubin diglucuronide. Although patients with the Crigler-Najjar syndrome (Type I) and Gunn rats lack UDP glucuronate glucuronyltransferase, their livers enzymatically convert bilirubin monoglucuronide to diglucuronide in vitro. Conversion in bilirubin monoglucuronide to diglucuronide was demonstrated in Gunn rats in vivo. PMID:96142

  4. Direct quantification of human serum albumin in human blood serum without separation of gamma-globulin by the total internal reflected resonance light scattering of thorium-sodium dodecylbenzene sulfonate at water/tetrachloromethane interface.

    PubMed

    Feng, Ping; Huang, Cheng Zhi; Li, Yuan Fang

    2002-09-01

    A direct quantification of human serum albumin (HSA) in blood serum samples without separation is proposed based on the measurements of total internal reflected resonance light scattering (TIR-RLS) at water/tetrachloromethane (H(2)O/CCl(4)) interfaces. In the pH range of 6.37-6.59, the coadsorption of the binary complex of HSA-Th(IV) with sodium dodecylbenzene sulfonate occurs at the H(2)O/CCl(4) interface, forming an amphiphilic layer and displaying greatly enhanced TIR-RLS signals with the maximum peak located at 340-370 nm. The enhanced TIR-RLS intensity is in proportion to the HSA concentration in the range 0.15-1.0 micro gml(-1). The limit of detection is 14.4 ngml(-1). The contents of HSA in blood serum samples were determined with the recovery of 97.1-102.3% and RSD of 0.6-2.9%, which are identical to those obtained according to the spectrofluorimetric method using chrome azurol S. PMID:12234467

  5. 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.

  6. Influence of hemoglobin on non-invasive optical bilirubin sensing

    NASA Astrophysics Data System (ADS)

    Jiang, Jingying; Gong, Qiliang; Zou, Da; Xu, Kexin

    2012-03-01

    Since the abnormal metabolism of bilirubin could lead to diseases in the human body, especially the jaundice which is harmful to neonates. Traditional invasive measurements are difficult to be accepted by people because of pain and infection. Therefore, the real-time and non-invasive measurement of bilirubin is of great significance. However, the accuracy of currently transcutaneous bilirubinometry(TcB) is generally not high enough, and affected by many factors in the human skin, mostly by hemoglobin. In this talk, absorption spectra of hemoglobin and bilirubin have been collected and analyzed, then the Partial Least Squares (PLS) models have been built. By analyzing and comparing the Correlation and Root Mean Square Error of Prediction(RMSEP), the results show that the Correlation of bilirubin solution model is larger than that of the mixture solution added with hemoglobin, and its RMSEP value is smaller than that of mixture solution. Therefore, hemoglobin has influences on the non-invasive optical bilirubin sensing. In next step, it is necessary to investigate how to eliminate the influence.

  7. Fluorescent protein-based detection of unconjugated bilirubin in newborn serum

    PubMed Central

    Iwatani, Sota; Nakamura, Hajime; Kurokawa, Daisuke; Yamana, Keiji; Nishida, Kosuke; Fukushima, Sachiyo; Koda, Tsubasa; Nishimura, Noriyuki; Nishio, Hisahide; Iijima, Kazumoto; Miyawaki, Atsushi; Morioka, Ichiro

    2016-01-01

    Increased serum levels of unconjugated bilirubin are associated with the development of brain damage in newborns. In current clinical settings, there are no methods for directly determining serum levels of unconjugated bilirubin. UnaG, a fluorescent protein from Japanese eel muscle that specifically binds to unconjugated bilirubin was used in this study. Linear regression analysis was carried out to compare unconjugated bilirubin levels measured by UnaG and conventional bilirubin oxidase methods. Unconjugated bilirubin levels in the serum of newborns who were untreated or treated with phototherapy were compared. Effects of interfering factors in the serum (conjugated bilirubin, hemoglobin, and lipid) on unconjugated bilirubin concentration measured by the UnaG method were also evaluated. Unconjugated bilirubin levels measured by the UnaG method were highly correlated with those determined by the bilirubin oxidase assay. Unconjugated bilirubin levels determined by bilirubin oxidase and UnaG assays were similar in serum samples containing conjugated bilirubin. The performance of the UnaG assay was unaffected by phototherapy and the presence of serum hemoglobin and lipid emulsion. These results demonstrate the clinical applicability of the UnaG method for direct measurement of unconjugated bilirubin levels in newborn serum. PMID:27324682

  8. Fluorescent protein-based detection of unconjugated bilirubin in newborn serum.

    PubMed

    Iwatani, Sota; Nakamura, Hajime; Kurokawa, Daisuke; Yamana, Keiji; Nishida, Kosuke; Fukushima, Sachiyo; Koda, Tsubasa; Nishimura, Noriyuki; Nishio, Hisahide; Iijima, Kazumoto; Miyawaki, Atsushi; Morioka, Ichiro

    2016-01-01

    Increased serum levels of unconjugated bilirubin are associated with the development of brain damage in newborns. In current clinical settings, there are no methods for directly determining serum levels of unconjugated bilirubin. UnaG, a fluorescent protein from Japanese eel muscle that specifically binds to unconjugated bilirubin was used in this study. Linear regression analysis was carried out to compare unconjugated bilirubin levels measured by UnaG and conventional bilirubin oxidase methods. Unconjugated bilirubin levels in the serum of newborns who were untreated or treated with phototherapy were compared. Effects of interfering factors in the serum (conjugated bilirubin, hemoglobin, and lipid) on unconjugated bilirubin concentration measured by the UnaG method were also evaluated. Unconjugated bilirubin levels measured by the UnaG method were highly correlated with those determined by the bilirubin oxidase assay. Unconjugated bilirubin levels determined by bilirubin oxidase and UnaG assays were similar in serum samples containing conjugated bilirubin. The performance of the UnaG assay was unaffected by phototherapy and the presence of serum hemoglobin and lipid emulsion. These results demonstrate the clinical applicability of the UnaG method for direct measurement of unconjugated bilirubin levels in newborn serum. PMID:27324682

  9. Surface receptors for serum albumin in group C and G streptococci show three different types of albumin specificity.

    PubMed Central

    Wideback, K; Kronvall, G

    1982-01-01

    A total of 100 bacterial strains were tested for binding uptake of radiolabeled albumin preparations from 15 mammalian species. Three types of surface structures with specific binding sites for albumin were defined. A previously described receptor for albumin was separated into type a in Streptococcus equisimilis strains and in human group G streptococcal strains and type b in bovine group C streptococci. A new type of albumin receptor, type c, was found in Streptococcus dysgalactiae strains, the only receptor type so far with high affinity for bovine serum albumin. Type of albumin receptor correlated with bacterial species. The three receptor types showed high binding capacities; 2 X 10(8) bacterial organisms bound from 5 to 16 micrograms of albumin. All types of albumin receptors were stable to heat treatment at 80 degrees C for 5 min, but susceptible to both pepsin and trypsin treatment. Bacteria-bound albumin preparations were eluted at various concentrations of KSCN, reflecting differences in affinity. Up to 500 micrograms of human fibrinogen or polyclonal human immunoglobulin G had no inhibitory effect on the uptake of albumin, indicating a separate molecular localization of receptors for these proteins. PMID:6295942

  10. Bilirubin oxidases in bioelectrochemistry: features and recent findings.

    PubMed

    Mano, Nicolas; Edembe, Lise

    2013-12-15

    Bilirubin oxidases, a sub class of the Multicopper oxidases family, were discovered in 1981 by Tanaka and Murao (Murao and Tanaka, 1981) and first used for the detection of bilirubin. Since 2001 and the pioneering work of Tsujimura, these BODs have attracted a lot of attention for the reduction of O2. Unlike laccases, these BODs are stable in physiological conditions (20mM phosphate buffer, pH 7.4, 0.14 M NaCl, 37 °C) and more than 120 papers have been published in the last 7 years. Here, we will first briefly describe some general features of BODs and then review the use of BODs for bilirubin biosensors and the recent achievements and progress toward the elaboration of efficient O2 reducing cathodes. PMID:23911663

  11. [Micelle-mediated extraction for concentrating conjugated bilirubin in urine].

    PubMed

    Matsudo, T; Saitoh, T; Matsubara, C

    2001-02-01

    An extraction method based on the phase separation of aqueous micellar solutions of n-octyl-beta-D-thioglucoside (OTG) was applied to the concentrating conjugated bilirubin in urine. The analyte in sample solutions could be efficiently concentrated into a small volume of surfactant-rich phase, while hydrophilic matrix components including urinary protein, ascorbic acid, and saccharide remained in the aqueous phase. The concentrated OTG negligibly affected the diazo reaction and the subsequent spectrophotometric detection. Conjugated bilirubin was successfully determined in the concentration range from 0.05 microgram/ml to 5 micrograms/ml with a 96-well microplate reader absorption spectrophotometer. PMID:11218735

  12. Galactosaemia: an unusual cause of chronic bilirubin encephalopathy.

    PubMed

    Sahoo, Tanushree; Thukral, Anu; Agarwal, Ramesh; Sankar, Mari Jeeva

    2015-01-01

    Galactosaemia is a disorder of galactose metabolism in which raised levels of galactose and galactose-1-phosphate damage various organs. Although galactosaemia is a common metabolic liver disease in childhood, it is a rare cause of neonatal hyperbilirubinemia requiring intervention. We report an unusual case of neonatal galactosaemia that at presentation had features of acute bilirubin encephalopathy requiring exchange transfusion and at discharge had features of chronic bilirubin encephalopathy. This case report emphasises the need for timely suspicion and diagnosis of this disease for prevention of chronic morbidity. PMID:25618877

  13. Serum Bilirubin and 6-min Walk Distance as Prognostic Predictors for Inoperable Chronic Thromboembolic Pulmonary Hypertension: A Prospective Cohort Study

    PubMed Central

    Gong, Juan-Ni; Zhai, Zhen-Guo; Yang, Yuan-Hua; Liu, Yan; Gu, Song; Kuang, Tu-Guang; Xie, Wan-Mu; Miao, Ran; Wang, Chen

    2015-01-01

    Background: Inoperable chronic thromboembolic pulmonary hypertension (CTEPH) is a severe clinical syndrome characterized by right cardiac failure and possibly subsequent liver dysfunction. However, whether serum markers of liver dysfunction can predict prognosis in inoperable CTEPH patients has not been determined. Our study aimed to evaluate the potential role of liver function markers (such as serum levels of transaminase, bilirubin, and gamma-glutamyl transpeptidase [GGT]) combined with 6-min walk test in the prediction of prognosis in patients with inoperable CTEPH. Methods: From June 2005 to May 2013, 77 consecutive patients with inoperable CTEPH without confounding co-morbidities were recruited for this prospective cohort study. Baseline clinical characteristics and 6-min walk distance (6MWD) results were collected. Serum biomarkers of liver function, including levels of aspartate aminotransferase, alanine aminotransferase, GGT, uric acid, and serum bilirubin, were also determined at enrollment. All-cause mortality was recorded during the follow-up period. Results: During the follow-up, 22 patients (29%) died. Cox regression analyses demonstrated that increased serum concentration of total bilirubin (hazard ratio [HR] = 7.755, P < 0.001), elevated N-terminal of the prohormone brain natriuretic peptide (HR = 1.001, P = 0.001), decreased 6MWD (HR = 0.990, P < 0.001), increased central venous pressure (HR = 1.074, P = 0.040), and higher pulmonary vascular resistance (HR = 1.001, P = 0.018) were associated with an increased risk of mortality. Serum concentrations of total bilirubin (HR = 4.755, P = 0.007) and 6MWD (HR = 0.994, P = 0.017) were independent prognostic predictors for CTEPH patients. Patients with hyperbilirubinemia (≥23.7 μmol/L) had markedly worse survival than those with normobilirubinemia. Conclusion: Elevated serum bilirubin and decreased 6MWD are potential predictors for poor prognosis in inoperable CTEPH. PMID:26612283

  14. 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.

  15. BILIRUBIN CONCENTRATIONS IN CLINICALLY HEALTHY AND DISEASED CAPTIVE WATERBUCK (KOBUS ELLIPSIPRYMNUS) AT THE SAN DIEGO ZOO SAFARI PARK.

    PubMed

    Sadler, Ryan A; Lamberski, Nadine; Christopher, Mary M

    2016-06-01

    Captive waterbuck ( Kobus ellipsiprymnus ) that appear clinically healthy have been noted to have high serum bilirubin concentrations compared with other ruminants; however, questions remain about the physiologic factors affecting bilirubin concentration and its potential association with underlying disease and icteric serum or mucous membranes. Serum bilirubin concentrations of healthy and diseased waterbuck housed at the San Diego Zoo Safari Park from 1989 to 2012 were retrospectively analyzed to determine any link between icteric serum, total bilirubin concentration (tBili), and disease entities in this species. Total bilirubin and direct (dBili) bilirubin concentrations and the prevalence of icteric serum were compared by subspecies, age group, and health status; associations with complete blood count and biochemical results and clinical diagnosis were assessed. No significant differences were found in tBili or dBili between Ellipsen (n = 32) and Defassa (n = 29) subspecies or in juveniles (n = 22) versus adults (n = 39). Clinically healthy waterbuck (n = 40) had significantly higher tBili (mean ± 2SD, 7.9 ± 1.2 mg/dl; P < 0.001) and dBili (3.7 ± 1.0 mg/dl; P < 0.001) than did diseased waterbuck (n = 21; tBili: 4.9 ± 2.56 mg/dl; dBili: 2.2 ± 0.8 mg/dl). No waterbuck had icteric tissues on physical examination. Twelve (19.7%) waterbuck (six healthy, six diseased) had icteric serum. Few minor correlations were seen between tBili or dBili and clinical, laboratory, or necropsy evidence of disease, though an inverse correlation between dBili and blood glucose was noted. Of the 40 healthy animals, reference intervals were calculated for tBili (5.5-10.3 mg/dl), dBili (1.7-5.7 mg/dl), and indirect bilirubin (2.2-6.2 mg/dl). These results suggest healthy waterbuck have relatively high tBili and dBili compared with related species. Icteric serum may be seen in up to 15% of healthy animals in the absence of icteric tissues. PMID:27468025

  16. Higher Serum Direct Bilirubin Levels Were Associated with a Lower Risk of Incident Chronic Kidney Disease in Middle Aged Korean Men

    PubMed Central

    Ryu, Seungho; Chang, Yoosoo; Zhang, Yiyi; Woo, Hee-Yeon; Kwon, Min-Jung; Park, Hyosoon; Lee, Kyu-Beck; Son, Hee Jung; Cho, Juhee; Guallar, Eliseo

    2014-01-01

    Background The association between serum bilirubin levels and incident chronic kidney disease (CKD) in the general population is unknown. We aimed to examine the association between serum bilirubin concentration (total, direct, and indirect) and the risk of incident CKD. Methods and Findings Longitudinal cohort study of 12,823 Korean male workers 30 to 59 years old without CKD or proteinuria at baseline participating in medical health checkup program in a large worksite. Study participants were followed for incident CKD from 2002 through 2011. Estimated glomerular filtration rate (eGFR) was estimated by using the CKD-EPI equation. CKD was defined as eGFR <60 mL/min per 1.73 m2. Parametric Cox models and pooled logistic regression models were used to estimate adjusted hazard ratios for incident CKD. We observed 238 incident cases of CKD during 70,515.8 person-years of follow-up. In age-adjusted models, the hazard ratios for CKD comparing quartiles 2–4 vs. quartile 1 of serum direct bilirubin were 0.93 (95% CI 0.67–1.28), 0.88 (0.60–1.27) and 0.60 (0.42–0.88), respectively. In multivariable models, the adjusted hazard ratio for CKD comparing the highest to the lowest quartile of serum direct bilirubin levels was 0.60 (95% CI 0.41–0.87; P trend = 0.01). Neither serum total nor indirect bilirubin levels were significantly associated with the incidence of CKD. Conclusions Higher serum direct bilirubin levels were significantly associated with a lower risk of developing CKD, even adjusting for a variety of cardiometabolic parameters. Further research is needed to elucidate the mechanisms underlying this association and to establish the role of serum direct bilirubin as a marker for CKD risk. PMID:24586219

  17. Nanofibrous polymeric beads from aramid fibers for efficient bilirubin removal.

    PubMed

    Peng, Zihang; Yang, Ye; Luo, Jiyue; Nie, Chuanxiong; Ma, Lang; Cheng, Chong; Zhao, Changsheng

    2016-08-16

    Polymer based hemoperfusion has been developed as an effective therapy to remove the extra bilirubin from patients. However, the currently applied materials suffer from either low removal efficiency or poor blood compatibility. In this study, we report the development of a new class of nanofibrous absorbent that exhibited high bilirubin removal efficiency and good blood compatibility. The Kevlar nanofiber was prepared by dissolving micron-sized Kevlar fiber in proper solvent, and the beads were prepared by dropping Kevlar nanofiber solutions into ethanol. Owing to the nanofiborous structure of the Kevlar nanofiber, the beads displayed porous structures and large specific areas, which would facilitate the adsorption of toxins. In the adsorption test, it was noticed that the beads possessed an adsorption capacity higher than 40 mg g(-1) towards bilirubin. In plasma mimetic solutions, the beads still showed high bilirubin removal efficiency. Furthermore, after incorporating with carbon nanotubes, the beads were found to have increased adsorption capacity for human degradation waste. Moreover, the beads showed excellent blood compatibility in terms of a low hemolysis ratio, prolonged clotting times, suppressed coagulant activation, limited platelet activation, and inhibited blood related inflammatory activation. Additionally, the beads showed good compatibility with endothelial cells. In general, the Kevlar nanofiber beads, which integrated with high adsorption capacity, good blood compatibility and low cytotoxicity, may have great potential for hemoperfusion and some other applications in biomedical fields. PMID:27481656

  18. Biphasic Effect of Rifampicin on Bilirubin- A Case Report.

    PubMed

    Gopi, Manigandan; Seshadri, Mandalam Subramanian

    2016-04-01

    Drug induced hepatitis is a major problem which a physician encounters in his clinical practice. In view of increasing incidence of tuberculosis in our country a large number of infected individuals are started on Antituberculous (ATT) drugs and rifampicin is invariably part of the regimen. One of the major adverse effects of ATT drugs is drug- induced hepatitis which is characterized by elevation of liver enzymes and bilirubin. Hepatotoxicity is usually idiosyncratic or dose-dependent. Rifampicin causes transient elevation of transaminases in 10-20 percent of individuals and this does not warrant dose adjustments of the drug. Rarely rifampicin can lead to severe hepatitis with hyperbilirubinaemia and marked elevations of SGOT and SGPT and in some patients this can be fatal. The exact mechanism of Rifampicin induced hepatotoxicity is not known but it is postulated to be due to idiosyncratic reaction to rifampicin metabolites which may be directly toxic or induce an immunologically mediated liver injury. Rarely rifampicin may cause hyperbilirubinaemia without enzyme elevation. Here we report a patient with bilateral pulmonary tuberculosis who developed transient severe indirect hyperbilirubinaemia on rifampicin. On review of relevant literature we find that rifampicin can have a biphasic effect on bilirubin, an initial increase in indirect bilirubin and later normalization of bilirubin. We have reported this case because of its rarity in clinical practice. PMID:27190870

  19. Biphasic Effect of Rifampicin on Bilirubin- A Case Report

    PubMed Central

    Seshadri, Mandalam Subramanian

    2016-01-01

    Drug induced hepatitis is a major problem which a physician encounters in his clinical practice. In view of increasing incidence of tuberculosis in our country a large number of infected individuals are started on Antituberculous (ATT) drugs and rifampicin is invariably part of the regimen. One of the major adverse effects of ATT drugs is drug- induced hepatitis which is characterized by elevation of liver enzymes and bilirubin. Hepatotoxicity is usually idiosyncratic or dose-dependent. Rifampicin causes transient elevation of transaminases in 10-20 percent of individuals and this does not warrant dose adjustments of the drug. Rarely rifampicin can lead to severe hepatitis with hyperbilirubinaemia and marked elevations of SGOT and SGPT and in some patients this can be fatal. The exact mechanism of Rifampicin induced hepatotoxicity is not known but it is postulated to be due to idiosyncratic reaction to rifampicin metabolites which may be directly toxic or induce an immunologically mediated liver injury. Rarely rifampicin may cause hyperbilirubinaemia without enzyme elevation. Here we report a patient with bilateral pulmonary tuberculosis who developed transient severe indirect hyperbilirubinaemia on rifampicin. On review of relevant literature we find that rifampicin can have a biphasic effect on bilirubin, an initial increase in indirect bilirubin and later normalization of bilirubin. We have reported this case because of its rarity in clinical practice. PMID:27190870

  20. Solar Irradiation of Bilirubin: An Experiment in Photochemical Oxidation

    ERIC Educational Resources Information Center

    Pillay A. E.; Salih, F. M.

    2006-01-01

    An experiment in photochemical oxidation, which deals with bilirubin, a well-known light-sensitive biological compound that is pedagogically ideal for photochemical experiments at tertiary institutes, is presented. The experiment would benefit students in chemistry who eventually branch out into the health sciences or biochemistry.

  1. The pharmacological features of bilirubin: the question of the century.

    PubMed

    Zahir, Farhana; Rabbani, Gulam; Khan, Rizwan Hasan; Rizvi, Shamim J; Jamal, Mohammad Sarwar; Abuzenadah, Adel M

    2015-09-01

    This review looks at the toxicity and metabolism of bilirubin in terms of its pharmacological potential. Its role has gained importance as more research has revealed the functional significance and interrelationship between the gasotransmitters nitric oxide and carbon monoxide. The biological actions of bilirubin have mostly been characterized in the high micromolar range where toxic effects occur. However, it could also prove to be an important cytoprotector for brain tissue, which is inherently less equipped for antioxidant defense. Plasma bilirubin levels negatively correlate to a number of disease states. Higher levels of bilirubin that are still within the normal range provide a protective effect to the body. The effects on various disorders could be tested using controlled pharmacological upregulation of the molecule with animal models. At nanomolar concentrations, considerable benefits have been obtained when the molecule was delivered pharmacologically under in vitro or in vivo test conditions, particularly in neurodegenerative disorders and after tissue or organ transplantation. The induction of heme oxygenase-1 (HMOX-1) via the activation of nuclear factor erythroid 2-related factor or the use of bile pigments in the harvesting of diseased tissue are novel applications, and like every new therapy, should be used with caution. HMOX-1 is tissue specific, and in exceptional states, such as schizophrenia and specific types of renal disorder, the same therapy may have disastrous effects. PMID:26208389

  2. Distant Determination of Bilirubin Distribution in Skin by Multi-Spectral Imaging

    NASA Astrophysics Data System (ADS)

    Saknite, I.; Jakovels, D.; Spigulis, J.

    2011-01-01

    For mapping the bilirubin distribution in bruised skin the multi-spectral imaging technique was employed, which made it possible to observe temporal changes of the bilirubin content in skin photo-types II and III. The obtained results confirm the clinical potential of this technique for skin bilirubin diagnostics.

  3. Twenty-five years of progress in bilirubin metabolism (1952-77).

    PubMed Central

    Billing, B H

    1978-01-01

    This review deals with the development of our understanding of the chemistry of bilirubin and its glucuronide derivatives during the years 1952-1977. It examines the relation between haem metabolism and bilirubin formation and our present knowledge of hepatic transport of bilirubin. The heterogeneity of familial hyperbilirubinaemia is discussed. PMID:98394

  4. Influence of black cohosh (Cimicifuga racemosa) use by postmenopausal women on total hepatic perfusion and liver functions.

    PubMed

    Nasr, Ahmed; Nafeh, Hanan

    2009-11-01

    In this prospective longitudinal clinical trial, 87 postmenopausal women receiving for 12 consecutive months a daily dose of 40 mg of a dry extract preparation of Cimicifuga racemosa (Klimadynon) for relief of vasomotor symptoms were followed up by evaluation of total hepatic blood flow, assessed by color Doppler ultrasound, as well as prothrombin time and concentration, serum albumin, bilirubin, gamma-glutamyltransferase, alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase. Because no significant changes in total hepatic blood flow or any of the liver functions tested were reported, we concluded that use of C. racemosa for 1 year by healthy postmenopausal women without evidence of liver disease does not seem to influence the liver. PMID:19539907

  5. Serum albumin: touchstone or totem?

    PubMed

    Margarson, M P; Soni, N

    1998-08-01

    A decrease in serum albumin concentrations is an almost inevitable finding in disease states, and is primarily mediated in the acute phase by alterations in vascular permeability and redistribution. This change is not disease specific but marked changes that persist are generally associated with a poorer prognosis. Critical appraisal of long-standing practices and the availability of alternative colloid solutions have led to a reduction in albumin replacement therapy, and a widespread tolerance of lower albumin concentrations in patients. The factors determining serum albumin concentrations, their measurement and the implications of hypoalbuminaemia are reviewed. The clinical value of serum albumin measurement is discussed. PMID:9797524

  6. Interaction of cucurbitacins with human serum albumin: Thermodynamic characteristics and influence on the binding of site specific ligands.

    PubMed

    Abou-Khalil, Rony; Jraij, Alia; Magdalou, Jacques; Ouaini, Naïm; Tome, Daniel; Greige-Gerges, Hélène

    2009-06-01

    Cucurbitacins (Cuc) are cytotoxic oxygenated triterpenes. Their binding to albumin may control their diffusion and consequently their biological effects. The specific binding site of Cuc to albumin is important to be defined as it could determine some of the drug interactions of the compounds. This paper deals with the interaction between human serum albumin and a series of four cucurbitacins (B, D, E and I) measured by fluorescence and circular dichroism spectroscopies. Cuc B and E at C25, are the acetylated forms of Cuc D and I. The binding parameters (K(a) and n) of Cuc B, D and E to albumin were determined at 288, 293, 298 and 303K. Cuc B possesses the higher binding constant (K(a)) values followed by Cuc E and D. The thermodynamic parameters DeltaH, DeltaG and DeltaS were calculated. They indicated hydrophobic and electrostatic interactions for Cuc B, hydrophobic interaction for Cuc E, hydrophobic and hydrogen bond interactions for Cuc D. In addition to bilirubin, Cuc B, D, and E increased the binding constant values for warfarin to albumin, whereas they did not affect the binding of other ligands of site I such as chloroform and salicylate. The increase of the K(a) values of warfarin and bilirubin was associated with an increase of the binding constant value of cucurbitacin to albumin. Cuc I did not bind to albumin and could be considered less capable to affect the interaction of ligands to albumin than Cuc B, D and E. CD spectra indicated that Cuc binding to HSA was not associated with substantial structural changes of the protein. PMID:19380237

  7. Multistimuli-Responsive Bilirubin Nanoparticles for Anticancer Therapy.

    PubMed

    Lee, Yonghyun; Lee, Soyoung; Lee, Dong Yun; Yu, Byeongjun; Miao, Wenjun; Jon, Sangyong

    2016-08-26

    Although stimuli-responsive materials hold potential for use as drug-delivery carriers for treating cancers, their clinical translation has been limited. Ideally, materials used for the purpose should be biocompatible and nontoxic, provide "on-demand" drug release in response to internal or external stimuli, allow large-scale manufacturing, and exhibit intrinsic anticancer efficacy. We present multistimuli-responsive nanoparticles formed from bilirubin, a potent endogenous antioxidant that possesses intrinsic anticancer and anti-inflammatory activity. Exposure of the bilirubin nanoparticles (BRNPs) to either reactive oxygen species (ROS) or external laser light causes rapid disruption of the BRNP nanostructure as a result of a switch in bilirubin solubility, thereby releasing encapsulated drugs. In a xenograft tumor model, BRNPs loaded with the anticancer drug doxorubicin (DOX@BRNPs), when combined with laser irradiation of 650 nm, significantly inhibited tumor growth. This study suggests that BRNPs may be used as a drug-delivery carrier as well as a companion medicine for effectively treating cancers. PMID:27485478

  8. Bilirubin oxidation products (BOXes): synthesis, stability and chemical characteristics

    PubMed Central

    Wurster, W. L.; Pyne-Geithman, G. J.; Peat, I. R.; Clark, J. F.

    2009-01-01

    Summary Bilirubin oxidation products (BOXes) have been a subject of interest in neurosurgery because they are purported to be involved in subarachnoid hemorrhage induced cerebral vasospasm. There is a growing body of information concerning their putative role in vasospasm; however, there is a dearth of information concerning the chemical and biochemical characteristics of BOXes. A clearer understanding of the synthesis, stability and characteristics of BOXes will be important for a better understanding of the role of BOXes post subarachnoid hemorrhage. We used hydrogen peroxide to oxidize bilirubin and produce BOXes. BOXes were extracted and analyzed using conventional methods such as HPLC and mass spectrometry. Characterization of the stability BOXes demonstrates that light can photodegrade BOXes with a t1/2 of up to 10 h depending upon conditions. Mixed isomers of BOXes have an apparent extinction coefficient of ε = 6985, and a λmax of 310 nm. BOXes are produced by the oxidation of bilirubin, yielding a mixture of isomers: 4-methyl-5-oxo-3-vinyl-(1,5-dihydropyrrol-2-ylidene)acetamide (BOX A) and 3-methyl-5-oxo-4-vinyl-(1,5-dihydropyrrol-2-ylidene)acetamide (BOX B). The BOXes are photodegraded by ambient light and can be analyzed spectrophotometrically with their extinction coefficient as well as with HPLC or mass spectrometry. Their small molecular weight and photodegradation may have made them difficult to characterize in previous studies. PMID:18456996

  9. Bilirubin binding with liver cystatin induced structural and functional changes.

    PubMed

    Mustafa, Mir Faisal; Bano, Bilqees

    2014-05-01

    Cysteine proteinases and their inhibitors play a significant role in the proteolytic environment of the cells. Inhibitors of cysteine proteinases regulate the activity of these enzymes helping in checking the degdration activity of cathepsins. The bilirubin secreated by liver cells can bind to cystatin present in the liver resulting in its functional inactivation, which may further lead to the increase in cathepsins level causing liver cirrhosis. In case of some pathophysiological conditions excess bilirubin gets accumulated e.g. in presence of Fasciola hepatica (liver fluke) in mammals and humans, leading to liver cirrhosis and possibly jaundice or normal blockade of bile duct causing increased level of bilirubin in blood. Protease-cystatin imbalance causes disease progression. In the present study, Bilirubin (BR) and liver cystatin interaction was studied to explore the cystatin inactivation and structural alteration. The binding interaction was studied by UV-absorption, FT-IR and fluorescence spectroscopy. The quenching of protein fluorescence confirmed the binding of BR with buffalo liver cystatin (BLC). Stern-Volmer analysis of BR-BLC system indicates the presence of static component in the quenching mechanism and the number of binding sites to be close to 1. The fluorescence data proved that the fluorescence quenching of liver cystatin by BR was the result of BR-cystatin complex formation. FTIR analysis of BR-Cystatin complex revealed change in the secondary structure due to perturbation in the microenvironment further confirmed by the decreased caseinolytic activity of BLC against papain. Fluorescence measurements also revealed quenching of fluorescence and shift in peak at different time intervals and at varying pH values. Photo-illumination of BR-cystatin complex causes change in the surrounding environment of liver cystatin as indicated by red-shift. The binding constant for BR-BLC complex was found to be 9.279 × 10(4) M(-1). The cystatin binding with

  10. Inhibitory Effects of Palm Tocotrienol-Rich Fraction Supplementation on Bilirubin-Metabolizing Enzymes in Hyperbilirubinemic Adult Rats

    PubMed Central

    Kamisah, Yusof; Lim, Jing Jye; Lim, Chew-Lian; Asmadi, Ahmad Y.

    2014-01-01

    Background Phenylhydrazine, a hemolytic agent, is widely used as a model of experimental hyperbilirubinemia. Palm tocotrienol-rich fraction (TRF) was shown to exert beneficial effects in hyperbilirubinemic rat neonates. Aim To investigate the effects of palm TRF supplementation on hepatic bilirubin-metabolizing enzymes and ocidative stress status in rats administered phenylhydrazine. Methods Twenty-four male Wistar rats were divided into two groups; one group was intraperitoneally injected with palm TRF at the dose of 30 mg/kg/day, while another group was only given vehicle (control) (vitamin E-free palm oil) for 14 days. Twenty-four hours after the last dose, each group was further subdivided into another two groups. One group was administered phenylhydrazine (100 mg/kg, intraperitoneally) and another group was administered normal saline. Twenty-four hours later, blood and liver were collected for biochemical parameter measurements. Results Phenylhydrazine increased plasma total bilirubin level and oxidative stress in the erythrocytes as well as in the liver, which were reduced by the pretreatment of palm TRF. Palm TRF also prevented the increases in hepatic heme oxygenase, biliverdin reductase and UDP-glucuronyltransferase activities induced by phenylhydrazine. Conclusion Palm tocotrienol-rich fraction was able to afford protection against phenylhydrazine-induced hyperbilirubinemia, possibly by reducing oxidative stress and inhibiting bilirubin-metabolizing enzymes in the liver. PMID:24586630

  11. Predictive effects of bilirubin on response of colorectal cancer to irinotecan-based chemotherapy

    PubMed Central

    Yu, Qian-Qian; Qiu, Hong; Zhang, Ming-Sheng; Hu, Guang-Yuan; Liu, Bo; Huang, Liu; Liao, Xin; Li, Qian-Xia; Li, Zhi-Huan; Yuan, Xiang-Lin

    2016-01-01

    AIM: To examine the predictive effects of baseline serum bilirubin levels and UDP-glucuronosyltransferase (UGT) 1A1*28 polymorphism on response of colorectal cancer to irinotecan-based chemotherapy. METHODS: The present study was based on a prospective multicenter longitudinal trial of Chinese metastatic colorectal cancer (mCRC) patients treated with irinotecan-based chemotherapy (NCT01282658). Baseline serum bilirubin levels, including total bilirubin (TBil) and unconjugated bilirubin (UBil), were measured, and genotyping of UGT1A1*28 polymorphism was performed. Receiver operating characteristic curve (ROC) analysis was used to determine cutoff values of TBil and UBil. The TBil values were categorized into > 13.0 or ≤ 13.0 groups; the UBil values were categorized into > 4.1 or ≤ 4.1 groups. Combining the cutoff values of TBil and UBil, which was recorded as CoBil, patients were classified into three groups. The classifier’s performance of UGT1A1*28 and CoBil for predicting treatment response was evaluated by ROC analysis. Associations between response and CoBil or UGT1A1*28 polymorphism were estimated using simple and multiple logistic regression models. RESULTS: Among the 120 mCRC patients, the serum bilirubin level was significantly different between the UGT1A1*28 wild-type and mutant genotypes. Patients with the mutant genotype had an increased likelihood of a higher TBil (P = 0.018) and a higher UBil (P = 0.014) level compared with the wild-type genotype. Patients were stratified into three groups based on CoBil. Group 1 was patients with TBil > 13.0 and UBil > 4.1; Group 2 was patients with TBil ≤ 13.0 and UBil > 4.1; and Group 3 was patients with TBil ≤ 13.0 and UBil ≤ 4.1. Patients in Group 3 had more than a 10-fold higher likelihood of having a response in the simple (OR = 11.250; 95%CI: 2.286-55.367; P = 0.003) and multiple (OR = 16.001; 95%CI: 2.802 -91.371; P = 0.002) analyses compared with the Group 1 individuals. Patients carrying the UGT1

  12. 21 CFR 862.1115 - Urinary bilirubin and its conjugates (nonquantitative) test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1115 Urinary bilirubin and its conjugates (nonquantitative)...

  13. 21 CFR 862.1115 - Urinary bilirubin and its conjugates (nonquantitative) test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1115 Urinary bilirubin and its conjugates (nonquantitative)...

  14. 21 CFR 862.1115 - Urinary bilirubin and its conjugates (nonquantitative) test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1115 Urinary bilirubin and its conjugates (nonquantitative)...

  15. 21 CFR 862.1115 - Urinary bilirubin and its conjugates (nonquantitative) test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1115 Urinary bilirubin and its conjugates (nonquantitative)...

  16. 21 CFR 862.1115 - Urinary bilirubin and its conjugates (nonquantitative) test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1115 Urinary bilirubin and its conjugates (nonquantitative)...

  17. Unconjugated bilirubin mediates heme oxygenase-1-induced vascular benefits in diabetic mice.

    PubMed

    Liu, Jian; Wang, Li; Tian, Xiao Yu; Liu, Limei; Wong, Wing Tak; Zhang, Yang; Han, Quan-Bin; Ho, Hing-Man; Wang, Nanping; Wong, Siu Ling; Chen, Zhen-Yu; Yu, Jun; Ng, Chi-Fai; Yao, Xiaoqiang; Huang, Yu

    2015-05-01

    Heme oxygenase-1 (HO-1) exerts vasoprotective effects. Such benefit in diabetic vasculopathy, however, remains unclear. We hypothesize that bilirubin mediates HO-1-induced vascular benefits in diabetes. Diabetic db/db mice were treated with hemin (HO-1 inducer) for 2 weeks, and aortas were isolated for functional and molecular assays. Nitric oxide (NO) production was measured in cultured endothelial cells. Hemin treatment augmented endothelium-dependent relaxations (EDRs) and elevated Akt and endothelial NO synthase (eNOS) phosphorylation in db/db mouse aortas, which were reversed by the HO-1 inhibitor SnMP or HO-1 silencing virus. Hemin treatment increased serum bilirubin, and ex vivo bilirubin treatment improved relaxations in diabetic mouse aortas, which was reversed by the Akt inhibitor. Biliverdin reductase silencing virus attenuated the effect of hemin. Chronic bilirubin treatment improved EDRs in db/db mouse aortas. Hemin and bilirubin reversed high glucose-induced reductions in Akt and eNOS phosphorylation and NO production. The effect of hemin but not bilirubin was inhibited by biliverdin reductase silencing virus. Furthermore, bilirubin augmented EDRs in renal arteries from diabetic patients. In summary, HO-1-induced restoration of endothelial function in diabetic mice is most likely mediated by bilirubin, which preserves NO bioavailability through the Akt/eNOS/NO cascade, suggesting bilirubin as a potential therapeutic target for clinical intervention of diabetic vasculopathy. PMID:25475440

  18. Bilirubin scavenges chloramines and inhibits myeloperoxidase-induced protein/lipid oxidation in physiologically relevant hyperbilirubinemic serum.

    PubMed

    Boon, A C; Hawkins, C L; Coombes, J S; Wagner, K H; Bulmer, A C

    2015-09-01

    Hypochlorous acid (HOCl), an oxidant produced by myeloperoxidase (MPO), induces protein and lipid oxidation, which is implicated in the pathogenesis of atherosclerosis. Individuals with mildly elevated bilirubin concentrations (i.e., Gilbert syndrome; GS) are protected from atherosclerosis, cardiovascular disease, and related mortality. We aimed to investigate whether exogenous/endogenous unconjugated bilirubin (UCB), at physiological concentrations, can protect proteins/lipids from oxidation induced by reagent and enzymatically generated HOCl. Serum/plasma samples supplemented with exogenous UCB (≤250µM) were assessed for their susceptibility to HOCl and MPO/H2O2/Cl(-) oxidation, by measuring chloramine, protein carbonyl, and malondialdehyde (MDA) formation. Serum/plasma samples from hyperbilirubinemic Gunn rats and humans with GS were also exposed to MPO/H2O2/Cl(-) to: (1) validate in vitro data and (2) determine the relevance of endogenously elevated UCB in preventing protein and lipid oxidation. Exogenous UCB dose-dependently (P<0.05) inhibited HOCl and MPO/H2O2/Cl(-)-induced chloramine formation. Albumin-bound UCB efficiently and specifically (3.9-125µM; P<0.05) scavenged taurine, glycine, and N-α-acetyllysine chloramines. These results were translated into Gunn rat and GS serum/plasma, which showed significantly (P<0.01) reduced chloramine formation after MPO-induced oxidation. Protein carbonyl and MDA formation was also reduced after MPO oxidation in plasma supplemented with UCB (P<0.05; 25 and 50µM, respectively). Significant inhibition of protein and lipid oxidation was demonstrated within the physiological range of UCB, providing a hypothetical link to protection from atherosclerosis in hyperbilirubinemic individuals. These data demonstrate a novel and physiologically relevant mechanism whereby UCB could inhibit protein and lipid modification by quenching chloramines induced by MPO-induced HOCl. PMID:26057938

  19. Bilirubin as a Protective Factor for Rheumatoid Arthritis: An NHANES Study of 2003 - 2006 Data

    PubMed Central

    Fischman, Daniel; Valluri, Ashok; Gorrepati, Venkata Subhash; Murphy, Megan E.; Peters, Ian; Cheriyath, Pramil

    2010-01-01

    Background Rheumatoid arthritis(RA) is a chronic inflammatory, autoimmune polyarthritis, with a prevalence estimated at one percent of the United States(US) population. Serum bilirubin, because of its antioxidant nature, has been conjectured to exert an anti-inflammatory biologic effect. The objective of this study is to discern whether higher serum Total Bilirubin(TBili) levels are protective against RA. Methods This is a secondary analysis of National Health and Nutrition Examination Survey (NHANES) data collected between 2003-2006. Study participants completed a comprehensive questionnaire regarding their health history, underwent a physical examination, and had body fluids collected for laboratory studies. In NHANES, to assess for the presence of RA, the following questions were asked: "Doctor ever said you had arthritis?" If so, "Which type of arthritis". Statistical analysis was performed, using SAS version 9.1, proc survey methods. Participant data were adjusted for demographic characteristics as well as risk factors for RA. Results NHANES 2003-2006 included 20,470 individuals, chosen as a representative sampling of the entire US population. Exclusion criteria included age less than twenty years or liver dysfunction, defined as history of abnormal liver function tests or liver disease. 8,147 subjects did not have any exclusion criteria and were included in the data analysis. RA is inversely related to the serum level of TBili with an odds ratio of 0.679 (95% CI 0.533-0.865) and remained significant even after adjusting for age, gender, race, education, and tobacco history, with an odds ratio 0.749 (95% CI 0.575 - 0.976). Conclusions Our study supports the hypothesis that higher TBili levels are protective against RA. A plausible mechanism for this association would be that the anti-oxidant effects of TBili exert a physiologic anti-inflammatory effect, which provides protection against RA. This explanation is supported by prior studies which show that higher

  20. Albumin impregnated vascular grafts: albumin resorption and tissue reactions.

    PubMed

    Cziperle, D J; Joyce, K A; Tattersall, C W; Henderson, S C; Cabusao, E B; Garfield, J D; Kim, D U; Duhamel, R C; Greisler, H P

    1992-01-01

    This study aimed to determine the kinetics of albumin resorption from and the healing of two types of albumin impregnated Vasculour II (Bard Cardiovascular) Dacron grafts (ACG-A and ACG-B) using whole blood preclotted Vasculour II Dacron grafts (without albumin) as controls (PCC). Prostheses measuring 4 mm ID x 50 mm length were implanted in the aortoiliac position in 24 dogs (ACG-A n = 12, ACG-B n = 24, PCC n = 12) and explanted after 1, 2 4, and 6 months. Platelet count, platelet aggregometry to 10(-5) M ADP, prothrombin time (PT), and partial thromboplastin time (PTT) were determined preoperatively and at explantation. Sections of the explanted grafts were assayed for human albumin by immunohistochemical techniques utilizing a rabbit polyclonal mono-specific antibody for human albumin followed by the addition of a biotinylated goat anti-rabbit IgG. Immunoperoxidase staining was then performed using Avidin D horse-radish peroxidase. Histology of the grafts (light microscopy, scanning electron microscopy, and transmission electron microscopy) as well as percent thrombus free surface area (TFSA) by computerized planimetry were also determined. Seven of 48 grafts were occluded (85.4% patency) with no difference among the three groups. Platelet aggregometry was not predictive of graft patency. No change in PT or PTT occurred nor was there any difference among the three groups. Retained albumin was detected in every one-month explant but not beyond that time, with the sensitivity for detecting human albumin in this assay being 20 mg albumin per gram of Dacron. All ACG explants at one month revealed inner capsular fibrin coagula not present in PCC specimens.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1388174

  1. Purification, characterization and decolorization of bilirubin oxidase from Myrothecium verrucaria 3.2190

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Myrothecium verrucaria 3.2190 is a nonligninolytic fungus that produces bilirubin oxidase. Both Myrothecium verrucaria and the extracellular bilirubin oxidase were tested for their ability to decolorize indigo carmine. The biosorption and biodegradation of the dye were detected during the process of...

  2. Protein-Support Interactions for Rationally Designed Bilirubin Oxidase Based Cathode: A Computational Study.

    PubMed

    Matanovic, Ivana; Babanova, Sofia; Chavez, Madelaine Seow; Atanassov, Plamen

    2016-04-21

    An example of biocathode based on bilirubin oxidase (BOx) was used to demonstrate how density functional theory can be combined with docking simulations in order to study the interface interactions between the enzyme and specifically designed electrode surface. The electrode surface was modified through the adsorption of bilirubin, the natural substrate for BOx, and the prepared electrode was electrochemically characterized using potentiostatic measurements. The experimentally determined current densities showed that the presence of bilirubin led to significant improvement of the cathode operation. On the basis of the computationally calculated binding energies of bilirubin to the graphene support and BOx and the analysis of the positioning of bilirubin relative to the support and T1 Cu atom of the enzyme, we hypothesize that the bilirubin serves as a geometric and electronic extension of the support. The computational results further confirm that the modification of the electrode surface with bilirubin provides an optimal orientation of BOx toward the support but also show that bilirubin facilitates the interfacial electron transfer by decreasing the distance between the electrode surface and the T1 Cu atom. PMID:27015361

  3. Reproducibility and intragastric variation of duodenogastric reflux using ambulatory gastric bilirubin monitoring.

    PubMed

    Manifold, D K; Anggiansah, A; Marshall, R E; Owen, W J

    2001-01-01

    Duodenogastric reflux has long been considered to be important in the pathogenesis of many gastric disorders that exhibit regional variation within the stomach. Ambulatory gastric bilirubin monitoring is a new technique and, although extensively validated, reproducibility and gastric regional variation have not been specifically addressed. Fourteen patients with symptoms of gastroesophageal reflux and 12 healthy subjects underwent 24-h ambulatory gastric bilirubin monitoring with the bilirubin sensor in the upper stomach. Gastric bilirubin monitoring with two simultaneous bilirubin probes, one in the upper stomach and the other in the antrum, was performed on a separate occasion. Gastric bilirubin exposure in the initial and repeat studies showed a good correlation (R = 0.60, P < 0.01). Gastric bilirubin exposure in the upper stomach and the antrum showed a high degree of correlation (R = 0.90, P < 0.01). In conclusion, reproducible results are obtained with ambulatory gastric bilirubin monitoring and duodenogastric reflux does not exhibit significant regional variation within the stomach. PMID:11270798

  4. Bilirubin content and 4-nitrophenol glucuronosyltransferase activity in Gunn rat liver.

    PubMed

    Celier, C; Foliot, A

    1984-04-01

    The purpose of this study was to determine whether the hepatic content of bilirubin could influence liver 4-nitrophenolglucuronosyltransferase (4-NP-GT) in the Gunn rat. In animals fed on a 45% lipid diet, compared with rats fed on a normal lipid diet (3%), the bilirubin content of the hepatic microsomal fraction decreased and the bilirubin/protein ratio was reduced. 4-NP-GT activities were comparable in both groups. Administration of clofibrate to Gunn rats greatly enhanced the bilirubin content of liver microsomal fraction. Since this treatment raised the microsomal protein content, the bilirubin/protein ratio was not modified. No significant change in 4-NP-GT was noted. After bilirubin perfusion in Gunn and Wistar rats, no change was observed in hepatic monooxygenase activities or in 4-NP-GT, although the bilirubin/protein ratio was dramatically increased in the microsomal fraction. From these results the low activity of liver 4-NP-GT in Gunn rats does not seem directly related to the hepatic content of bilirubin. PMID:6421531

  5. Relationship of Bilirubin Levels in Infancy to Later Intellectual Development. Interim Report No. 20.

    ERIC Educational Resources Information Center

    Rubin, Rosalyn A.; And Others

    The relationship of bilirubin (a red bile pigment that is sometimes found in the urine and occurs in the blood and tissues in jaundice) in infancy to later intellectual development was investigated in 241 infants with moderately elevated and high bilirubin levels. Ss were administered motor, psycholinguistic, and intelligence tests at age 8…

  6. Hepatocellular uptake of sulfobromophthalein and bilirubin is selectively inhibited by an antibody to the liver plasma membrane sulfobromophthalein/bilirubin binding protein.

    PubMed Central

    Stremmel, W; Berk, P D

    1986-01-01

    To clarify sulfobromophthalein (BSP) and bilirubin uptake mechanisms, isolated rat hepatocytes were incubated with [35S]BSP. The initial uptake velocity (V0), determined from the first, linear portion of the cumulative uptake curve, was saturable (Michaelis constant [Km] = 6.2 +/- 0.5 microM; Vmax = 638 +/- 33 pmol X min-1 per 10(5) hepatocytes), maximal at 37 degrees C and pH 7.4, and competitively inhibited by bilirubin, but not by taurocholate, cholate, or oleate. Preloading with unlabeled BSP led to trans-stimulation of V0. Sodium substitution or pretreatment of hepatocytes with ouabain or metabolic inhibitors had no effect on V0; trypsin reduced V0 by 39% (P less than 0.001). A rabbit antiserum to the rat liver plasma membrane (LPM)-BSP/bilirubin binding protein selectively reduced V0 of 5 microM [35S]BSP and [14C]bilirubin by 41 and 42%, respectively (P less than 0.01); uptakes of [3H]oleate, [3H]cholate and [3H]taurocholate were not affected. Hence, the LPM-BSP/bilirubin binding protein plays a role in the carrier-mediated uptake of BSP and bilirubin by hepatocytes. PMID:3745441

  7. Revalidation and rationale for high pKa values of unconjugated bilirubin

    PubMed Central

    Ostrow, J Donald; Mukerjee, Pasupati

    2007-01-01

    Background Our prior solvent partition analysis, published in 1992, yielded pKa values for unconjugated bilirubin of about 8.1 and 8.4, but these results have been challenged and studies by other methods have suggested pKa values below 5.0. Methods We repeated our published solvent partition studies, using 14C-unconjugated bilirubin highly purified by extraction of residual labeled impurities from CHCl3 into an aqueous buffer, pH 7.0. Partition ratios at six pH values from 5.0 to 9.0 were determined by radioassay and compared with our prior values obtained by diazo assay. Results At pH values ranging from 4.8 to 9.2, stable aqueous/chloroform 14C-partition ratios did not differ significantly from our published partition ratios based on diazo assay. Conclusion These results support the high pKa values of unconjugated bilirubin, above 8.0, derived from our earlier solvent partition study. In both studies, our measurements were based on the rapid analysis of clearly under-saturated solutions of highly-purified bilirubin over a wide pH range, using properly purified and preserved solvents. No previous direct estimate of the aqueous pKa values of unconjugated bilirubin meets all these preconditions. Three theoretical factors acting in combination, each related to the unique, extensive internal H-bonding of the -COOH groups, are proposed to support high pKa values of unconjugated bilirubin in water: a) donation of an H-bond from the -OH moiety of the -COOH group, which is broken on ionization; b) hindered solvation of the -COO- group after ionization; and c) restricted rotation of the -COO- and -COOH groups. Our findings and rationale rebut methodological and theoretical criticisms leveled against our prior work. High pKa values for unconjugated bilirubin dictate that: a) bilirubin diacid, which readily diffuses across membranes and can cause neurotoxicity, is the dominant unbound bilirubin species of unconjugated bilirubin in plasma at physiological pH; b) at the near

  8. Metabolism of bilirubin by human cytochrome P450 2A6

    SciTech Connect

    Abu-Bakar, A'edah; Arthur, Dionne M.; Wikman, Anna S.; Rahnasto, Minna; Juvonen, Risto O.; Vepsäläinen, Jouko; Raunio, Hannu; Ng, Jack C.; Lang, Matti A.

    2012-05-15

    The mouse cytochrome P450 (CYP) 2A5 has recently been shown to function as hepatic “Bilirubin Oxidase” (Abu-Bakar, A., et al., 2011. Toxicol. Appl. Pharmacol. 257, 14–22). To date, no information is available on human CYP isoforms involvement in bilirubin metabolism. In this paper we provide novel evidence for human CYP2A6 metabolising the tetrapyrrole bilirubin. Incubation of bilirubin with recombinant yeast microsomes expressing the CYP2A6 showed that bilirubin inhibited CYP2A6-dependent coumarin 7-hydroxylase activity to almost 100% with an estimated K{sub i} of 2.23 μM. Metabolite screening by a high-performance liquid chromatography/electrospray ionisation mass spectrometry indicated that CYP2A6 oxidised bilirubin to biliverdin and to three other smaller products with m/z values of 301, 315 and 333. Molecular docking analyses indicated that bilirubin and its positively charged intermediate interacted with key amino acid residues at the enzyme's active site. They were stabilised at the site in a conformation favouring biliverdin formation. By contrast, the end product, biliverdin was less fitting to the active site with the critical central methylene bridge distanced from the CYP2A6 haem iron facilitating its release. Furthermore, bilirubin treatment of HepG2 cells increased the CYP2A6 protein and activity levels with no effect on the corresponding mRNA. Co-treatment with cycloheximide (CHX), a protein synthesis inhibitor, resulted in increased half-life of the CYP2A6 compared to cells treated only with CHX. Collectively, the observations indicate that the CYP2A6 may function as human “Bilirubin Oxidase” where bilirubin is potentially a substrate and a regulator of the enzyme. -- Highlights: ► Human CYP2A6 interacts with bilirubin with a high affinity. ► Bilirubin docking to the CYP2A6 active site is more stable than biliverdin docking. ► Recombinant CYP2A6 microsomes metabolised bilirubin to biliverdin. ► Bilirubin increased the hepatic CYP2

  9. Multiple Genetic Modifiers of Bilirubin Metabolism Involvement in Significant Neonatal Hyperbilirubinemia in Patients of Chinese Descent

    PubMed Central

    Yang, Hui; Zheng, Lei; Lin, Min; Zheng, Xiang-bin; Lin, Fen

    2015-01-01

    The potential for genetic variation to modulate neonatal hyperbilirubinemia risk is increasingly being recognized. A case-control study was designed to assess comprehensive contributions of the multiple genetic modifiers of bilirubin metabolism on significant neonatal hyperbilirubinemia in Chinese descendents. Eleven common mutations and polymorphisms across five bilirubin metabolism genes, namely those encoding UGT1A1, HMOX1, BLVRA, SLCO1B1 and SLCO1B3, were determined using the high resolution melt (HRM) assay or PCR-capillary electrophoresis analysis. A total of 129 hyperbilirubinemic infants and 108 control subjects were evaluated. Breastfeeding and the presence of the minor A allele of rs4148323 (UGTA*6) were correlated with an increased risk of hyperbilirubinemia (OR=2.17, P=0.02 for breastfeeding; OR=9.776, P=0.000 for UGTA*6 homozygote; OR=3.151, P=0.000 for UGTA*6 heterozygote); whereas, increasing gestational age and the presence of –TA7 repeat variant of UGT1A1 decreased the risk (OR=0.721, P=0.003 for gestational age; OR=0.313, P=0.002 for heterozygote TA6/TA7). In addition, the SLCO1B1 and SLCO1B3 polymorphisms also contributed to an increased risk of hyperbilirubinemia. This detailed analysis revealed the impact of multiple genetic modifiers on neonatal hyperbilirubinemia. This may support the use of genetic tests for clinical risk assessment. Furthermore, the established HRM assay can serve as an effective method for large-scale investigation. PMID:26146841

  10. Hepatic bilirubin UDP-glucuronyltransferase in patients with sickle cell anemia.

    PubMed

    Maddrey, W C; Cukier, J O; Maglalang, A C; Boitnott, J K; Odell, G B

    1978-02-01

    In sickle cell anemia the shortened survival of red blood cells presents the liver with an augmented load of bilirubin for hepatic clearance. To determine the effects of this excessive bilirubin load on the microsomal conjugating enzyme, hepatic bilirubin UDP-glucuronyltransferase, levels of this enzyme were measured in liver biopsies from patients with sickle cell anemia and several comparison groups. UDP-glucuronyltransferase activity in 14 patients with sickle cell anemia was 2-fold greater (P less than 0.005) than in 14 nonjaundiced comparison patients without liver disease. The elevated UDP-glucuronyltransferase activity in sickle cell anemia was similar to that found in 10 patients who chronically ingested drugs (barbiturates or estrogens) known to increase UDP-glucuronyltransferase activity. These observations suggest enhanced conjugation of bilirubin in patients with sickle cell anemia may result from substrate (bilirubin) induction of UDP-glycuronyltransferase. PMID:413760

  11. Metabolism of heme and bilirubin in rat and human small intestinal mucosa.

    PubMed Central

    Hartmann, F; Bissell, D M

    1982-01-01

    Formation of heme, bilirubin, and bilirubin conjugates has been examined in mucosal cells isolated from the rat upper small intestine. Intact, viable cells were prepared by enzymatic dissociation using a combined vascular and luminal perfusion and incubated with an isotopically labeled precursor, delta-amino-[2,3-3H]levulinic acid. Labeled heme and bile pigment were formed with kinetics similar to those exhibited by hepatocytes. Moreover, the newly formed bilirubin was converted rapidly to both mono- and diglucuronide conjugates. In addition, cell-free extracts of small intestinal mucosa from rats or humans exhibited a bilirubin-UDP-glucuronyl transferase activity that was qualitatively similar to that present in liver. The data suggest that the small intestinal mucosa normally contributes to bilirubin metabolism. PMID:6806320

  12. Caveolae-Dependent and -Independent Uptake of Albumin in Cultured Rodent Pulmonary Endothelial Cells

    PubMed Central

    Li, Hui-Hua; Li, Jin; Wasserloos, Karla J.; Wallace, Callen; Sullivan, Mara G.; Bauer, Philip M.; Stolz, Donna B.; Lee, Janet S.; Watkins, Simon C.; St Croix, Claudette M.; Pitt, Bruce R.; Zhang, Li-Ming

    2013-01-01

    Although a critical role for caveolae-mediated albumin transcytosis in pulmonary endothelium is well established, considerably less is known about caveolae-independent pathways. In this current study, we confirmed that cultured rat pulmonary microvascular (RPMEC) and pulmonary artery (RPAEC) endothelium endocytosed Alexa488-labeled albumin in a saturable, temperature-sensitive mode and internalization resulted in co-localization by fluorescence microscopy with cholera B toxin and caveolin-1. Although siRNA to caveolin-1 (cav-1) in RPAEC significantly inhibited albumin uptake, a remnant portion of albumin uptake was cav-1-independent, suggesting alternative pathways for albumin uptake. Thus, we isolated and cultured mouse lung endothelial cells (MLEC) from wild type and cav-1-/- mice and noted that ~ 65% of albumin uptake, as determined by confocal imaging or live cell total internal reflectance fluorescence microscopy (TIRF), persisted in total absence of cav-1. Uptake of colloidal gold labeled albumin was evaluated by electron microscopy and demonstrated that albumin uptake in MLEC from cav-1-/- mice was through caveolae-independent pathway(s) including clathrin-coated pits that resulted in endosomal accumulation of albumin. Finally, we noted that albumin uptake in RPMEC was in part sensitive to pharmacological agents (amiloride [sodium transport inhibitor], Gö6976 [protein kinase C inhibitor], and cytochalasin D [inhibitor of actin polymerization]) consistent with a macropinocytosis-like process. The amiloride sensitivity accounting for macropinocytosis also exists in albumin uptake by both wild type and cav-1-/- MLEC. We conclude from these studies that in addition to the well described caveolar-dependent pulmonary endothelial cell endocytosis of albumin, a portion of overall uptake in pulmonary endothelial cells is cav-1 insensitive and appears to involve clathrin-mediated endocytosis and macropinocytosis-like process. PMID:24312378

  13. Enterohepatic circulation of nonconjugated bilirubin in rats fed with human milk

    SciTech Connect

    Alonso, E.M.; Whitington, P.F.; Whitington, S.H.; Rivard, W.A.; Given, G. )

    1991-03-01

    To test the hypothesis that enhanced intestinal absorption of bilirubin may contribute to prolonged nonconjugated hyperbilirubinemia in human milk-fed infants, we studied a cross-section of 36 healthy infants and mothers. Milk from mothers and serum from infants were collected at 16.3 +/- 2.4 days. Milk was studied for its effect on the absorption of bilirubin labeled with carbon 14 in rats and compared with buffer and iron-fortified infant formula (Similac With Iron). The percentage of a 1 mg bilirubin dose absorbed by the rat was 25.29 +/- 4.0% when it was administered into the duodenum with buffer, 4.67 +/- 2.4% with Similac formula, and 7.7 +/- 2.9% with human milk. Linear regression analysis, using the infant's serum nonconjugated bilirubin level as the dependent variable and the percentage of (14C)bilirubin absorbed by the rat with the corresponding mother's milk as the independent variable, revealed a significant correlation (r = 0.40; p = 0.016). Inspection of the data suggested that absorptive permissiveness correlated closely with infant serum bilirubin values greater than 24 mumol/L (1.4 mg/dl) (r = 0.55; p = 0.007), whereas in those with bilirubin values less than or equal to 24 mumol/L, there was no apparent correlation. Milk was also analyzed for beta-glucuronidase, nonesterified fatty acids, and the ability to inhibit glucuronosyltransferase activity of rat liver microsomes in vitro, none of which correlated with the infant's serum bilirubin. These data support the theory that enhanced intestinal absorption of bilirubin contributes to the jaundice associated with breast-feeding.

  14. Does Serum Bilirubin level on admission predict TIMI flow grade and in-hospital MACE in patients with STEMI undergoing primary PCI.

    PubMed

    Celik, Turgay; Kaya, Mehmet G; Akpek, Mahmut; Yarlioglues, Mikail; Sarli, Bahadir; Topsakal, Ramazan; Gibson, Charles Michael

    2014-03-01

    We evaluated the association of total bilirubin with post-percutaneous coronary intervention (PCI) coronary blood flow and in-hospital major adverse cardiac events (MACEs) in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary PCI. A total of 536 consecutive patients with STEMI (male 79%, mean age = 59.9 ± 12.6 years) admitted within 6 hours from symptom onset were enrolled. Patients were divided into 2 groups based on the thrombolysis in myocardial infarction (MI) flow grade. In-stent thrombosis, nonfatal MI, and in-hospital mortality were significantly higher in no-reflow group (P = .007, P = .002, and P < .001, respectively). On multivariate regression, the total bilirubin levels remained independent predictors of no-reflow (odds ratio [OR] 1.586, 95% confidence interval [CI] 1.02-2.47; P = .042) and in-hospital MACE (OR 1.399, 95% CI 1.053-1.857; P = .020). Serum bilirubin levels were independently associated with no-reflow and in-hospital MACE in patients with STEMI undergoing primary PCI. PMID:23378197

  15. Amadori albumin in diabetic nephropathy.

    PubMed

    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

  16. Bilirubin as a Determinant for Altered Neurogenesis, Neuritogenesis, and Synaptogenesis

    PubMed Central

    Fernandes, Adelaide; Falcão, Ana Sofia; Abranches, Elsa; Bekman, Evguenia; Henrique, Domingos; Lanier, Lorene M.; Brites, Dora

    2009-01-01

    Elevated levels of serum unconjugated bilirubin (UCB) in the first weeks of life may lead to long-term neurologic impairment. We previously reported that an early exposure of developing neurons to UCB, in conditions mimicking moderate to severe neonatal jaundice, leads to neuritic atrophy and cell death. Here, we have further analyzed the effect of UCB on nerve cell differentiation and neuronal development, addressing how UCB may affect the viability of undifferentiated neural precursor cells and their fate decisions, as well as the development of hippocampal neurons in terms of dendritic and axonal elongation and branching, the axonal growth cone morphology, and the establishment of dendritic spines and synapses. Our results indicate that UCB reduces the viability of proliferating neural precursors, decreases neurogenesis without affecting astrogliogenesis, and increases cellular dysfunction in differentiating cells. In addition, an early exposure of neurons to UCB decreases the number of dendritic and axonal branches at 3 and 9 days in vitro (DIV), and a higher number of neurons showed a smaller growth cone area. UCB-treated neurons also reveal a decreased density of dendritic spines and synapses at 21 DIV. Such deleterious role of UCB in neuronal differentiation, development, and plasticity may compromise the performance of the brain in later life. PMID:19449315

  17. A retrospective analysis of 25% human serum albumin supplementation in hypoalbuminemic dogs with septic peritonitis

    PubMed Central

    Horowitz, Farrah B.; Read, Robyn L.; Powell, Lisa L.

    2015-01-01

    This study describes the influence of 25% human serum albumin (HSA) supplementation on serum albumin level, total protein (TP), colloid osmotic pressure (COP), hospital stay, and survival in dogs with septic peritonitis. Records of 39 dogs with septic peritonitis were evaluated. In the HSA group, initial and post-transfusion TP, albumin, COP, and HSA dose were recorded. In the non-supplemented group, repeated values of TP, albumin, and COP were recorded over their hospitalization. Eighteen dogs survived (53.8% mortality). Repeat albumin values were higher in survivors (mean 23.9 g/L) and elevated repeat albumin values were associated with HSA supplementation. Repeat albumin and TP were higher in the HSA supplemented group (mean 24 g/L and 51.9 g/L, respectively) and their COP increased by 5.8 mmHg. Length of hospitalization was not affected. Twenty-five percent HSA increases albumin, TP, and COP in canine patients with septic peritonitis. Higher postoperative albumin levels are associated with survival. PMID:26028681

  18. Solvation and crystal effects in bilirubin studied by NMR spectroscopy and density functional theory.

    PubMed

    Rohmer, Thierry; Matysik, Jörg; Mark, Franz

    2011-10-27

    The open-chain tetrapyrrole compound bilirubin was investigated in chloroform and dimethyl sulfoxide solutions by liquid-state NMR and as solid by (1)H, (13)C, and (15)N magic-angle spinning (MAS) solid-state NMR spectroscopy. Density functional theory (DFT) calculations were performed to interpret the data, using the B3LYP exchange-correlation functional to optimize geometries and to compute NMR chemical shieldings by the gauge-including atomic orbital method. The dependence of geometries and chemical shieldings on the size of the basis sets was investigated for the reference molecules tetramethylsilane, NH(3), and H(2)O, and for bilirubin as a monomer and in clusters consisting of up to six molecules. In order to assess the intrinsic errors of the B3LYP approximation in calculating NMR shieldings, complete basis set estimates were obtained for the nuclear shielding values of the reference molecules. The experimental liquid-state NMR data of bilirubin are well reproduced by a monomeric bilirubin molecule using the 6-311+G(2d,p) basis set for geometry optimization and for calculating chemical shieldings. To simulate the bilirubin crystal, a hexameric model was required. It was constructed from geometry-optimized monomers using information from the X-ray structure of bilirubin to fix the monomeric entities in space and refined by partial optimization. Combining experimental (1)H-(13)C and (1)H-(15)N NMR correlation spectroscopy and density functional theory, almost complete sets of (1)H, (13)C, and (15)N chemical shift assignments were obtained for both liquid and solid states. It is shown that monomeric bilirubin in chloroform solution is formed by 3-vinyl anti conformers, while bilirubin crystals are formed by 3-vinyl syn conformers. This conformational change leads to characteristic differences between the liquid- and solid-state NMR resonances. PMID:21846145

  19. Extended mathematical model for "in vivo" quantification of the interaction betweeen atazanavir and bilirubin.

    PubMed

    Lozano, Roberto; Domeque, Nieves; Apesteguia, Alberto-Fermín

    2014-02-01

    The objective of the present work was to conduct an "in vivo" analysis of the atazanavir-bilirubin interaction. We developed a new mathematical approach to PK/PDPK models for competitive interaction based on the Michaelis-Menten equation, which was applied to patients with polymorphisms in the gene for UDP-glucuronosyltransferase 1A1 (UGT1A1). Atazanavir is known to induce concentration-dependent increases in bilirubin plasma levels. Thus, we employed our mathematical model to analyse rises in steady state atazanavir and bilirubin concentrations, ultimately plotting a nomogram for detection of suboptimal atazanavir exposure. Application of our model revealed that an absolute value or a steady state increase in bilirubin falling below 3.8Φ µmol/L (where Φ is a correction factor, =1 for UGT1A1 wild type and ≠1 for UGT1A1 variants) could be used to predict suboptimal atazanavir exposure and treatment failure. Thus, we have successfully established a new mathematical approach for pharmacodynamic-pharmacokinetic modelling of the interaction between atazanavir and bilirubin, as it relates to genetic variants of UGT1A1. Taken together, our findings indicate that bilirubin plasma levels represent a valuable marker of atazanavir exposure. PMID:24243081

  20. 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

  1. Thrombin stimulates albumin transcytosis in lung microvascular endothelial cells via activation of acid sphingomyelinase.

    PubMed

    Kuebler, Wolfgang M; Wittenberg, Claudia; Lee, Warren L; Reppien, Eike; Goldenberg, Neil M; Lindner, Karsten; Gao, Yizhuo; Winoto-Morbach, Supandi; Drab, Marek; Mühlfeld, Christian; Dombrowsky, Heike; Ochs, Matthias; Schütze, Stefan; Uhlig, Stefan

    2016-04-15

    Transcellular albumin transport occurs via caveolae that are abundant in lung microvascular endothelial cells. Stimulation of albumin transcytosis by proinflammatory mediators may contribute to alveolar protein leak in lung injury, yet the regulation of albumin transport and its underlying molecular mechanisms are so far incompletely understood. Here we tested the hypothesis that thrombin may stimulate transcellular albumin transport across lung microvascular endothelial cells in an acid-sphingomyelinase dependent manner. Thrombin increased the transport of fluorescently labeled albumin across confluent human lung microvascular endothelial cell (HMVEC-L) monolayers to an extent that markedly exceeds the rate of passive diffusion. Thrombin activated acid sphingomyelinase (ASM) and increased ceramide production in HMVEC-L, but not in bovine pulmonary artery cells, which showed little albumin transport in response to thrombin. Thrombin increased total caveolin-1 (cav-1) content in both whole cell lysates and lipid rafts from HMVEC-L, and this effect was blocked by inhibition of ASM or de novo protein biosynthesis. Thrombin-induced uptake of albumin into lung microvascular endothelial cells was confirmed in isolated-perfused lungs by real-time fluorescence imaging and electron microscopy of gold-labeled albumin. Inhibition of ASM attenuated thrombin-induced albumin transport both in confluent HMVEC-L and in intact lungs, whereas HMVEC-L treatment with exogenous ASM increased albumin transport and enriched lipid rafts in cav-1. Our findings indicate that thrombin stimulates transcellular albumin transport in an acid sphingomyelinase-dependent manner by inducing de novo synthesis of cav-1 and its recruitment to membrane lipid rafts. PMID:26851257

  2. Dexmedetomidine Attenuates Bilirubin-Induced Lung Alveolar Epithelial Cell Death In Vitro and In Vivo*

    PubMed Central

    Cui, Jian; Zhao, Hailin; Yi, Bin; Zeng, Jing; Lu, Kaizhi

    2015-01-01

    Objective: To investigate bilirubin-induced lung alveolar epithelial cell injury together with the protection afforded by dexmedetomidine. Design: Prospective, randomized, controlled study. Setting: Research laboratory. Subjects: Sprague Dawley rats. Interventions: Alveolar epithelial A549 cell lines were cultured and received bilirubin (from 0 to 160 μM) to explore the protective pathway of dexmedetomidine on bilirubin-induced alveolar epithelial cell injury assessed by immunochemistry and flow cytometry. Sprague-Dawley rats were subjected to common bile duct ligation surgery to explore the protective effect of dexmedetomidine on hyperbilirubinemia-induced alveolar epithelial cell injury and respiratory failure in comparison with the Sham (subjected to the surgery procedure but without bile duct ligation) or dexmedetomidine control (only received intraperitoneal injection of dexmedetomidine). Measurements and Main Results: In vitro, dexmedetomidine reversed the collapse of mitochondrial membrane potential (Δψm), upregulation of cytochrome C, B cell leukemia 2 associated X protein, and cleaved-caspase 3 and 9 in A549 epithelial cells with bilirubin challenge. Furthermore, dexmedetomidine reversed the arrest of cell cycle and the downregulation of the transforming growth factorβ, phosphorylated mammalian target of rapamycin, and p42/44 mitogen-activated protein kinase induced by bilirubin. In vivo, pulmonary edema and inflammation were found after common bile duct ligation. Bilirubin and Paco2 were significantly increased, and oxygen (Pao2) was significantly decreased in the blood of common bile duct ligation rats from the postsurgery day 7 to day 21 when compared with those in the sham controls, respectively (p < 0.01). Daily intraperitoneal injection of dexmedetomidine significantly alleviated the lung edema and injury and prevented respiratory failure. Conclusion: Our data both in vitro and in vivo demonstrated that dexmedetomidine protected alveolar

  3. Development of a System Model for Non-Invasive Quantification of Bilirubin in Jaundice Patients

    NASA Astrophysics Data System (ADS)

    Alla, Suresh K.

    Neonatal jaundice is a medical condition which occurs in newborns as a result of an imbalance between the production and elimination of bilirubin. Excess bilirubin in the blood stream diffuses into the surrounding tissue leading to a yellowing of the skin. An optical system integrated with a signal processing system is used as a platform to noninvasively quantify bilirubin concentration through the measurement of diffuse skin reflectance. Initial studies have lead to the generation of a clinical analytical model for neonatal jaundice which generates spectral reflectance data for jaundiced skin with varying levels of bilirubin concentration in the tissue. The spectral database built using the clinical analytical model is then used as a test database to validate the signal processing system in real time. This evaluation forms the basis for understanding the translation of this research to human trials. The clinical analytical model and signal processing system have been successful validated on three spectral databases. First spectral database is constructed using a porcine model as a surrogate for neonatal skin tissue. Samples of pig skin were soaked in bilirubin solutions of varying concentrations to simulate jaundice skin conditions. The resulting skins samples were analyzed with our skin reflectance systems producing bilirubin concentration values that show a high correlation (R2 = 0.94) to concentration of the bilirubin solution that each porcine tissue sample is soaked in. The second spectral database is the spectral measurements collected on human volunteers to quantify the different chromophores and other physical properties of the tissue such a Hematocrit, Hemoglobin etc. The third spectral database is the spectral data collected at different time periods from the moment a bruise is induced.

  4. Podocytes degrade endocytosed albumin primarily in lysosomes.

    PubMed

    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

  5. 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

  6. X-ray analysis of bilirubin oxidase from Myrothecium verrucaria at 2.3 Å resolution using a twinned crystal

    PubMed Central

    Mizutani, Kimihiko; Toyoda, Mayuko; Sagara, Kenta; Takahashi, Nobuyuki; Sato, Atsuko; Kamitaka, Yuji; Tsujimura, Seiya; Nakanishi, Yuji; Sugiura, Toshiyuki; Yamaguchi, Shotaro; Kano, Kenji; Mikami, Bunzo

    2010-01-01

    Bilirubin oxidase (BOD), a multicopper oxidase found in Myrothecium verrucaria, catalyzes the oxidation of bilirubin to biliverdin. Oxygen is the electron acceptor and is reduced to water. BOD is used for diagnostic analysis of bilirubin in serum and has attracted considerable attention as an enzymatic catalyst for the cathode of biofuel cells that work under neutral conditions. Here, the crystal structure of BOD is reported for the first time. Blue bipyramid-shaped crystals of BOD obtained in 2-methyl-2,4-pentanediol (MPD) and ammonium sulfate solution were merohedrally twinned in space group P63. Structure determination was achieved by the single anomalous diffraction (SAD) method using the anomalous diffraction of Cu atoms and synchrotron radiation and twin refinement was performed in the resolution range 33–2.3 Å. The overall organization of BOD is almost the same as that of other multicopper oxidases: the protein is folded into three domains and a total of four copper-binding sites are found in domains 1 and 3. Although the four copper-binding sites were almost identical to those of other multicopper oxidases, the hydrophilic Asn residue (at the same position as a hydrophobic residue such as Leu in other multicopper oxidases) very close to the type I copper might contribute to the characteristically high redox potential of BOD. PMID:20606269

  7. Urinary Albumin Excretion and Vascular Function in Rheumatoid Arthritis

    PubMed Central

    2016-01-01

    Rheumatoid arthritis (RA) is associated with significant cardiovascular (CV) morbidity and mortality. Increased urinary albumin excretion is a marker of CV risk. There are only few data on urinary albumin excretion in RA patients. Aim of the present study was to investigate urinary albumin excretion in RA patients and analyze, whether there is an association between urinary albumin excretion and vascular function as measured by the augmentation index (AIx). In a total of 341 participants (215 with RA, 126 without RA) urinary albumin-creatinine ratio (ACR) was determined and the AIx was measured. The Kolmogorov-Smirnov-test was used to cluster patient groups whose distributions of ACR can be considered to be equal. A crude analysis showed a median ACR of 6.6 mg/g in the RA group and 5.7 mg/g in patients without RA (P > 0.05). In order to account for diabetes (DM) we formed 4 distinct patient groups. Group 1: RA-/DM- (n = 74); group 2: RA+/DM- (n = 195); group 3: RA-/DM+ (n = 52); group 4: RA+/DM+ (n = 20). Clustering of these groups revealed two distinct patient groups: those without RA and DM, and those with either RA or DM or both. The latter group showed statistically significant higher ACR (median 8.1 mg/g) as the former (median 4.5 mg/g). We found no significant correlation between AIx and ACR. Urinary albumin excretion in patients with RA or DM or both is higher than in subjects without RA and DM. This can be seen as a sign of vascular alteration and increased CV risk in these patients. PMID:26955238

  8. Urinary Albumin Excretion and Vascular Function in Rheumatoid Arthritis.

    PubMed

    Pieringer, Herwig; Brummaier, Tobias; Piringer, Bettina; Auer-Hackenberg, Lorenz; Hartl, Andreas; Puchner, Rudolf; Pohanka, Erich; Schmid, Michael

    2016-03-01

    Rheumatoid arthritis (RA) is associated with significant cardiovascular (CV) morbidity and mortality. Increased urinary albumin excretion is a marker of CV risk. There are only few data on urinary albumin excretion in RA patients. Aim of the present study was to investigate urinary albumin excretion in RA patients and analyze, whether there is an association between urinary albumin excretion and vascular function as measured by the augmentation index (AIx). In a total of 341 participants (215 with RA, 126 without RA) urinary albumin-creatinine ratio (ACR) was determined and the AIx was measured. The Kolmogorov-Smirnov-test was used to cluster patient groups whose distributions of ACR can be considered to be equal. A crude analysis showed a median ACR of 6.6 mg/g in the RA group and 5.7 mg/g in patients without RA (P > 0.05). In order to account for diabetes (DM) we formed 4 distinct patient groups. Group 1: RA-/DM- (n = 74); group 2: RA+/DM- (n = 195); group 3: RA-/DM+ (n = 52); group 4: RA+/DM+ (n = 20). Clustering of these groups revealed two distinct patient groups: those without RA and DM, and those with either RA or DM or both. The latter group showed statistically significant higher ACR (median 8.1 mg/g) as the former (median 4.5 mg/g). We found no significant correlation between AIx and ACR. Urinary albumin excretion in patients with RA or DM or both is higher than in subjects without RA and DM. This can be seen as a sign of vascular alteration and increased CV risk in these patients. PMID:26955238

  9. Identification of a genetic alteration in the code for bilirubin UDP-glucuronosyltransferase in the UGT1 gene complex of a Crigler-Najjar type I patient.

    PubMed Central

    Ritter, J K; Yeatman, M T; Ferreira, P; Owens, I S

    1992-01-01

    Patients with Crigler-Najjar syndrome (CN) type I inherit an autosomal recessive trait for hyperbilirubinemia, which is characterized by the total absence of bilirubin UDP-glucuronosyltransferase (transferase) activity. The recent identification of two bilirubin transferase isoforms with identical carboxyl termini (Ritter, J. K., J. M. Crawford, and I. S. Owens. 1991. J. Biol. Chem. 266:1043-1047) led to the discovery of a unique locus, UGT1, which encodes a family of UDP-glucuronosyltransferase isozymes, including the two bilirubin forms (Ritter, J. K., F. Chen, Y. Y. Sheen, H. M. Tran, S. Kimura, M. T. Yeatman, and I. S. Owens. 1992. J. Biol. Chem. 267:3257-3261). The UGT1 locus features a complex of six overlapping transcriptional units encoding transferases, each of which shares the four most 3' exons (2, 3, 4, and 5) specifying the 3' half of the transferase coding regions (condons 289-533) and the entire 3' untranslated region of each mRNA. This gene model predicts that a single critical mutation in any of these four "common" exons may inactivate the entire family of encoded transferases. In agreement with this prediction, we show here that in the first CN type I individual analyzed (patient F.B.), a 13-bp deletion has occurred in exon 2. Analysis of product generated by the polymerase chain reaction and genomic DNA demonstrated that F.B. is homozygous for the defective allele (UGT1*FB), and that the consanguineous parents are both heterozygotic at this locus. The mutation is predicted to result in the synthesis of severely truncated bilirubin transferase isozymes that are lacking a highly conserved sequence in the carboxyl-terminus and the characteristic membrane (endoplasmic reticulum)-anchoring segment of the protein molecule. Images PMID:1634606

  10. Bilirubin modulated cytokines, growth factors and angiogenesis to improve cutaneous wound healing process in diabetic rats.

    PubMed

    Ram, Mahendra; Singh, Vishakha; Kumawat, Sanjay; Kant, Vinay; Tandan, Surendra Kumar; Kumar, Dinesh

    2016-01-01

    Bilirubin has shown cutaneous wound healing potential in some preliminary studies. Here we hypothesize that bilirubin facilitates wound healing in diabetic rats by modulating important healing factors/candidates and antioxidant parameters in a time-dependent manner. Diabetes was induced in male Wistar rats by streptozotocin. In all diabetic rats wounds were created under pentobarbitone anesthesia. All the rats were divided into two groups, of which one (control) was treated with ointment base and other with bilirubin ointment (0.3%). Wound closer measurement and tissue collection were done on days 3, 7, 14 and 19 post-wounding. The relative expressions of hypoxia inducible factor-1 alpha (HIF-1α), vascular endothelial growth factor (VEGF), stromal cell-derived factor-1 alpha (SDF-1α), transforming growth factor- beta1 (TGF-β1()), tumor necrosis factor-α (TNF-α) and interlukin-10 (IL-10) mRNA and proteins and the mRNA of interlukin-1 beta (IL-1β) and matrix metalloprteinase-9 (MMP-9) were determined in the wound tissues. CD-31 staining and collagen content were evaluated by immunohistochemistry and picrosirius red staining, respectively. Histopathological changes were assessed by H&E staining. The per cent wound closer was significantly higher from day 7 onwards in bilirubin-treated rats. HIF-1α, VEGF, SDF-1α, TGF-β1, IL-10 mRNA and protein levels were significantly higher on days 3, 7 and 14 in bilirubin-treated rats. The mRNA expression and protein level of TNF-α and the mRNA of IL-1β and MMP-9 were progressively and markedly reduced in bilirubin-treated rats. The collagen deposition and formation of blood vessels were greater in bilirubin-treated rats. Bilirubin markedly facilitated cutaneous wound healing in diabetic rats by modulating growth factors, cytokines, neovasculogenesis and collagen contents to the wound site. Topical application of bilirubin ointment might be of great use in cutaneous wound healing in diabetic patients. PMID:26679676

  11. Physiological Antioxidative Network of the Bilirubin System in Aging and Age-Related Diseases

    PubMed Central

    Kim, Sung Young; Park, Sang Chul

    2012-01-01

    Oxidative stress is detrimental to life process and is particularly responsible for aging and age-related diseases. Thus, most organisms are well equipped with a spectrum of biological defense mechanisms against oxidative stress. The major efficient antioxidative mechanism is the glutathione system, operating a redox cycling mechanism for glutathione utilization, which consists of glutathione and its peroxidase and reductase. However, this system is mainly effective for hydrophilic oxidants, while lipophilic oxidants require another scavenging system. Since many age-related pathological conditions are related to lipid peroxidation, especially in association with the aging process, the physiological role of the scavenging system for lipophilic oxidants should be considered. In this regard, the biliverdin to bilirubin conversion pathway, via biliverdin reductase (BVR), is suggested to be another major protective mechanism that scavenges lipophilic oxidants because of the lipophilic nature of bilirubin. The efficiency of this bilirubin system might be potentiated by operation of the intertwined bicyclic systems of the suggested redox metabolic cycle of biliverdin and bilirubin and the interactive control cycle of BVR and heme oxygenase. In order to combat oxidative stress, both antioxidative systems against hydrophilic and lipophilic oxidants are required to work cooperatively. In this regard, the roles of the bilirubin system in aging and age-related diseases are reassessed in this review, and their interacting networks are evaluated. PMID:22457648

  12. Potential Cardiovascular Risk Protection of Bilirubin in End-Stage Renal Disease Patients under Hemodialysis

    PubMed Central

    do Sameiro-Faria, Maria; Kohlova, Michaela; Ribeiro, Sandra; Rocha-Pereira, Petronila; Teixeira, Laetitia; Nascimento, Henrique; Reis, Flávio; Miranda, Vasco; Bronze-da-Rocha, Elsa; Quintanilha, Alexandre; Belo, Luís; Costa, Elísio; Santos-Silva, Alice

    2014-01-01

    We evaluated the potential cardiovascular risk protection of bilirubin in hemodialysis (HD) patients. An enlarged set of studies were evaluated in 191 HD patients, including hematological study, lipid profile, iron metabolism, nutritional, inflammatory markers, and dialysis adequacy. The TA duplication screening in the UDP-glucuronosyltransferase 1 A1 (UGT1A1) promoter region was also performed. The UGT1A1 genotype frequencies in HD patients were 49.2%, 42.4%, and 8.4% for 6/6, 6/7, and 7/7 genotypes, respectively. Although no difference was found in UGT1A1 genotype distribution between the three tertiles of bilirubin, significant differences were found with increasing bilirubin levels, namely, a decrease in platelet, leukocyte, and lymphocyte counts, transferrin, oxidized low-density lipoprotein (ox-LDL), ox-LDL/low-density lipoprotein cholesterol ratio, apolipoprotein (Apo) A, Apo B, and interleukin-6 serum levels and a significant increased concentration of hemoglobin, hematocrit, erythrocyte count, iron, transferrin saturation, Apo A/Apo B ratio, adiponectin, and paraoxonase 1 serum levels. After adjustment for age these results remained significant. Our data suggest that higher bilirubin levels are associated with beneficial effects in HD patients, by improving lipid profile and reducing the inflammatory grade, which might contribute to increase in iron availability. These results suggest a potential cardiovascular risk protection of bilirubin in HD patients. PMID:25276769

  13. Pro-healing effects of bilirubin in open excision wound model in rats.

    PubMed

    Ahanger, Azad A; Leo, Marie D; Gopal, Anu; Kant, Vinay; Tandan, Surendra K; Kumar, Dinesh

    2016-06-01

    Bilirubin, a by-product of heme degradation, has an important role in cellular protection. Therefore, we speculated that bilirubin could be of potential therapeutic value in wound healing. To validate the hypothesis, we used a full-thickness cutaneous wound model in rats. Bilirubin (30 mg/kg) was administered intraperitoneally every day for 9 days. The surface area of the wound was measured on days 0, 2, 4, 7 and 10 after the creation of the wound. The granulation tissue was collected on day 10 post-wounding for analysing various parameters of wound healing. Bilirubin treatment accelerated wound contraction and increased hydroxyproline and glucosamine contents. mRNA expression of pro-inflammatory factors such as intercellular cell adhesion molecule-1 (ICAM-1) and tumour necrosis factor-α (TNF-α) were down-regulated and that of anti-inflammatory cytokine interleukin-10 (IL-10) was up-regulated. The findings suggest that bilirubin could be a new agent for enhancing cutaneous wound healing. PMID:24947136

  14. An amperometric bilirubin biosensor based on a conductive poly-terthiophene-Mn(II) complex.

    PubMed

    Rahman, Md Aminur; Lee, Kyung-Sun; Park, Deog-Su; Won, Mi-Sook; Shim, Yoon-Bo

    2008-01-18

    An amperometric bilirubin biosensor was fabricated by complexing the Mn(II) ion with a conducting polymer and the final biosensor surface was coated with a thin polyethyleneimine (PEI) film containing an enzyme, ascorbate oxidase (AsOx). The complexation between poly-5,2'-5',2''-terthiophene-3-carboxylic acid (PolyTTCA) and Mn(II) through the formation of Mn-O bond was confirmed by XPS. The PolyTTCA-Mn(II) complex was also characterized using cyclic voltammetry. The PolyTTCA-Mn(II)/PEI-AsOx biosensor specifically detect bilirubin through the mediated electron transfer by the Mn(II) ion. To optimize the experimental condition, various experimental parameters such as pH, temperature, and applied potential were examined. A linear calibration plot for bilirubin was obtained between 0.1 microM and 50 microM with the detection limit of 40+/-3.8 nM. Interferences from other biological compounds, especially ascorbate and dopamine were efficiently minimized by coating the biosensor surface with PEI-AsOx. The bilirubin sensor exhibited good stability and fast response time (<5s). The applicability of this bilirubin sensor was tested in a human serum sample. PMID:17964773

  15. N-Methyl-d-Aspartate Receptor and Neuronal Nitric Oxide Synthase Activation Mediate Bilirubin-Induced Neurotoxicity

    PubMed Central

    Brito, Maria A; Vaz, Ana R; Silva, Sandra L; Falcão, Ana S; Fernandes, Adelaide; Silva, Rui FM; Brites, Dora

    2010-01-01

    Hyperbilirubinemia may lead to neurotoxicity and neuronal death. Although the mechanisms of nerve cell damage by unconjugated bilirubin (UCB) appear to involve a disruption of the redox status and excitotoxicity, the contribution of nitric oxide (NO·) and of N-methyl-d-aspartate (NMDA) glutamate receptors is unclear. We investigated the role of NO· and NMDA glutamate receptors in the pathways of nerve cell demise by UCB. Neurons were incubated with 100 μmol/L UCB, in the presence of 100 μmol/L human serum albumin for 4 h at 37ºC, alone or in combination with N-ω-nitro-l-arginine methyl ester (l-NAME) (an inhibitor of neuronal nitric oxide synthase [nNOS]), hemoglobin (an NO· scavenger) or (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801) (an NMDA-receptor antagonist). Exposure to UCB led to increased expression of nNOS and production of both NO· and cyclic guanosine 3′,5′-monophosphate (cGMP), along with protein oxidation and depletion of glutathione. These events concurred for cell dysfunction and death and were counteracted by l-NAME. Moreover, the UCB-induced loss of neuronal viability was abolished by hemoglobin, whereas the activation of nNOS and production of both NO· and cGMP were counteracted by MK-801, resulting in significant protection from cell dysfunction and death. These results reinforce the involvement of oxidative stress by showing that nerve cell damage by UCB is mediated by NO· and therefore is counteracted by NO· inhibitors or scavengers. Our findings strongly suggest that the activation of nNOS and neurotoxicity occur through the engagement of NMDA receptors. These data reveal a role for overstimulation of glutamate receptors in mediating oxidative damage by UCB. PMID:20593111

  16. A Humanized Mouse Model to Study Human Albumin and Albumin Conjugates Pharmacokinetics.

    PubMed

    Low, Benjamin E; Wiles, Michael V

    2016-01-01

    Albumin is a large, highly abundant protein circulating in the blood stream which is regulated and actively recycled via the neonatal Fc receptor (FcRn). In humans this results in serum albumin having an exceptional long half-life of ~21 days. Some time ago it was realized that these intrinsic properties could be harnessed and albumin could be used as a privileged drug delivery vehicle. However, active development of albumin based therapeutics has been hampered by the lack of economic, relevant experimental models which can accurately recapitulate human albumin metabolism and pharmacokinetics. In mice for example, introduced human albumin is not recycled and is catabolized rapidly. This is mainly due to the failure of mouse FcRn to bind human albumin consequently, human albumin has a half-life of only 2-3 days in mice. To overcome this we developed and characterized a humanized mouse model which is null for mouse FcRn and mouse albumin, but is transgenic for, and expressing functional human FcRn. Published data clearly demonstrate that upon injection of human albumin into this model animal that it accurately recapitulates human albumin FcRn dependent serum recycling, with human albumin now having a half-life ~24 days, closely mimicking that observed in humans. In this practical review we briefly review this model and outline its use for pharmacokinetic studies of human albumin. PMID:27150087

  17. Higher plasma bilirubin predicts veno-occlusive disease in early childhood undergoing hematopoietic stem cell transplantation with cyclosporine

    PubMed Central

    Kim, Kwi Suk; Moon, Aree; Kang, Hyoung Jin; Shin, Hee Young; Choi, Young Hee; Kim, Hyang Sook; Kim, Sang Geon

    2016-01-01

    AIM: To analyze the association between plasma bilirubin levels and veno-occlusive disease (VOD) in non-adult patients undergoing hematopoietic stem cell transplantation (HSCT) during cyclosporine therapy. METHODS: A total of 123 patients taking cyclosporine were evaluated using an electronic medical system at the Seoul National University Children’s Hospital from the years 2004 through 2011. Patients were grouped by age and analyzed for incidence and type of adverse drug reactions (ADRs) including VOD. RESULTS: The HSCT patients were divided into three age groups: G#1 ≥ 18; 9 ≤ G#2 ≤ 17; and G#3 ≤ 8 years of age). The majority of transplant donor types were cord blood transplantations. Most prevalent ADRs represented acute graft-vs-host disease (aGVHD) and VOD. Although the incidences of aGVHD did not vary among the groups, the higher frequency ratios of VOD in G#3 suggested that an age of 8 or younger is a risk factor for developing VOD in HSCT patients. After cyclosporine therapy, the trough plasma concentrations of cyclosporine were lower in G#3 than in G#1, indicative of its increased clearance. Moreover, in G#3 only, a maximal total bilirubin level (BILmax) of ≥ 1.4 mg/dL correlated with VOD incidence after cyclosporine therapy. CONCLUSION: HSCT patients 8 years of age or younger are more at risk for developing VOD, diagnosed as hyperbilirubinemia, tender hepatomegaly, and ascites/weight gain after cyclosporine therapy, which may be represented by a criterion of plasma BILmax being ≥ 1.4 mg/dL, suggestive of more sensitive VOD indication in this age group. PMID:27358786

  18. Magnetic Resonance Imaging of Bilirubin Encephalopathy: Current Limitations and Future Promise

    PubMed Central

    Wisnowski, Jessica L.; Panigrahy, Ashok; Painter, Michael J.; Watchko, Jon F.

    2014-01-01

    Infants with chronic bilirubin encephalopathy often demonstrate abnormal bilateral, symmetric, high-signal intensity on T2-weighted magnetic resonance imaging of the globus pallidus and subthalamic nucleus, consistent with the neuropathology of kernicterus. Early magnetic resonance imaging of at risk infants, while frequently showing increased T1-signal in these regions, may give false positive findings due to the presence of myelin in these structures. Advanced magnetic resonance imaging including diffusion-weighted imaging, magnetic resonance spectroscopy, and diffusion tensor imaging with tractography may shed new insights into the pathogenesis of bilirubin-induced brain injury and the neural basis of long-term disability in infants and children with chronic bilirubin encephalopathy. PMID:25267277

  19. Neonatal bilirubin management as an implementation example of interdisciplinary continuum of care tools.

    PubMed

    Thornton, Sidney N; Thompson, Bryce S; Millar, Jean A; Eggert, Larry D; Wilcox, Adam B

    2007-01-01

    Management of newborn bilirubin spans the inpatient and outpatient continuum of care. Intermountain Healthcare has developed and implemented a web-based tool for managing bilirubin that follows newborn patients across care settings and providers with a consistent plan of care. The underlying model for the tool is derived from published guidelines. The model divides the time-sensitive data into risk zones and associates each zone with the appropriate order set for follow-up care. The tool integrates Intermountain's Help2 infrastructure for authoring terms, guidelines, and order sets, with alerts, results, and data entry within the context of the care model. Implementation of the bilirubin management tool is shown to improve communication, ease workflow, and improve guideline compliance. Lessons learned from the implementation include recommendations for handling point-of-care laboratory data and managing archival views, which are insightful to health networks managing longitudinal data. PMID:18693932

  20. Role of bilirubin overproduction in revealing Gilbert's syndrome: is dyserythropoiesis an important factor?

    PubMed Central

    Metreau, J M; Yvart, J; Dhumeaux, D; Berthelot, P

    1978-01-01

    Gilbert's syndrome was diagnosed in 37 patients with unconjugated hyperbilirubinaemia without overt haemolysis or structural liver abnormality, who had a marked reduction in hepatic bilirubin UDP-glucuronosyltransferase activity (B-GTA) (as compared with that of 23 normal subjects). No significant correlation existed in these patients between serum bilirubin level and the values of B-GTA, thus suggesting that factors other than a low B-GTA must influence the degree of hyperbilirubinaemia in Gilbert's syndrome. Studies of 51Cr erythrocyte survival and 59Fe kinetics in 10 unselected patients demonstrated slight haemolysis in eight, whereas mild ineffective erythropoiesis was suggested in all from a low 24-hour incorporation of radioactive iron into circulating red cells. This overproduction of bilirubin resulting from mild haemolysis and perhaps dyserythropoiesis might reflect only an extreme degree of the normal situation. It certainly contributes to the hyperbilirubinaemia of Gilbert's syndrome and may play a major role in the manifestation of this condition. PMID:101425

  1. Bilirubin Encephalopathy in a Domestic Shorthair Cat With Increased Osmotic Fragility and Cholangiohepatitis.

    PubMed

    Contreras, E T; Giger, U; Malmberg, J L; Quimby, J M; Schaffer, P A

    2016-05-01

    A 7-month-old female domestic shorthair cat was diagnosed with chronic regenerative hemolytic anemia characterized by increased osmotic fragility of unknown etiology. At 13 months of age, the cat was evaluated for acute collapse. The cat was icteric with severe hyperbilirubinemia but no hematocrit changes. Severe obtundation and lateral recumbency progressed to tetraparesis and loss of proprioception in all 4 limbs, and a cerebellar or brainstem lesion was suspected. Postmortem examination revealed suppurative cholangiohepatitis and acute neuronal necrosis in the nuclei of the brainstem and cerebellum, consistent with bilirubin encephalopathy. This is the first known occurrence of cholangiohepatitis and bilirubin encephalopathy in an adult cat with chronic hemolytic anemia. Although rare, bilirubin encephalopathy should be considered a possible sequela to hyperbilirubinemia in adult patients. It remains unknown whether increased osmotic fragility was related to the cholangiohepatopathy. PMID:26354310

  2. Separation by thin-layer chromatography and structure elucidation of bilirubin conjugates isolated from dog bile.

    PubMed Central

    Heirwegh, K P; Fevery, J; Michiels, R; van Hees, G P; Compernolle, F

    1975-01-01

    1. A system for separation of bile pigments by t.l.c. and for their structure elucidation is presented. Separated bile pigments are characterized by t.l.c. of derived dipyrrolic azopigments. 2. At the tetrapyrrolic stage hydrolysis in strongly alkaline medium followed by t.l.c. demonstrates the presence of bilirubin-IIIalpha, -IXalpha and -XIIIalpha and allows assessment of their relative amounts. 3. Most structural information is derived from analysis of dipyrrolic azopigments. Such derivatives, obtained by treatment of separated bile pigments with diazotized ethyl anthranilate, were separated and purified by t.l.c. Micro methods showed (a) the nature of the dipyrrolic aglycone, (b) the nature of the bonds connecting aglycone to a conjugating group, (c) the ratio of vinyl/isovinyl isomers present in the aglycone and, (d) the nature of the conjugating groups (by suitable derivative formation and t.l.c. with reference to known compounds). 4. In bile of normal dogs at least 20 tetrapyrrolic, diazo-positive bile pigments could be recognized. Except for two pigments the tetrapyrrolic nucleus corresponded predominantly to bilirubin-IXalpha. All conjugated pigments had their conjugating groups connected in ester linkage to the tetrapyrrolic aglycone, Apart from bilirubin-IXalpha, monoconjugates and homogeneous and mixed diconjugates of bilirubin were demonstrated; conjugating groups of major importance were xylose, glucose and glucuronic acid. 5. Bilirubin isomer determination on native bile and isolated bile pigments, and dipyrrole-exchange assays with [14C8]bilirubin indicated (a) that the conjugates pre-exist in bile, and (b) that no significant dipyrrole exchange occurs during isolation of the pigments. PMID:1156357

  3. Reduction of bilirubin by targeting human heme oxygenase-1 through siRNA.

    PubMed

    Xia, Zhen-Wei; Li, Chun-E; Jin, You-Xin; Shi, Yi; Xu, Li-Qing; Zhong, Wen-Wei; Li, Yun-Zhu; Yu, Shan-Chang; Zhang, Zi-Li

    2007-04-01

    Neonatal hyperbilirubinemia is a common clinical condition caused mainly by the increased production and decreased excretion of bilirubin. Current treatment is aimed at reducing the serum levels of bilirubin. Heme oxygenase-1 (HO-1) is a rate-limiting enzyme that generates bilirubin. In this study we intended to suppress HO-1 using the RNA interference technique. Small interfering RNA (siRNA)-A, -B, and -C were designed based on human HO-1 (hHO-1) mRNA sequences. siRNA was transfected into a human hepatic cell line (HL-7702). hHO-1 transcription and protein levels were then determined. In addition, the inhibitory effect of siRNA on hHO-1 was assessed in cells treated with hemin or transfected with an hHO-1 plasmid. siRNA-C showed the most potent suppressive effect on hHO-1. This inhibition is dose and time dependent. Compared with control, both hemin and hHO-1 plasmids up-regulated hHO-1 expression in HL-7702 cells. However, the up-regulation was significantly attenuated by siRNA-C. Furthermore, the decrease in hHO-1 activity was coincident with the suppression of its transcription. Finally, siRNA-C was shown to reduce hHO-1 enzymatic activity and bilirubin levels. Thus, this study provides a novel therapeutic rationale by blocking bilirubin formation via siRNA for preventing and treating neonatal hyperbilirubinemia and bilirubin encephalopathy at an early clinical stage. PMID:17392485

  4. Shank2 Regulates Renal Albumin Endocytosis

    PubMed Central

    Dobrinskikh, Evgenia; Lewis, Linda; Doctor, R Brian; Okamura, Kayo; Lee, Min Goo; Altmann, Christopher; Faubel, Sarah; Kopp, Jeffrey B; Blaine, Judith

    2015-01-01

    Albuminuria is a strong and independent predictor of kidney disease progression but the mechanisms of albumin handling by the kidney remain to be fully defined. Previous studies have shown that podocytes endocytose albumin. Here we demonstrate that Shank2, a large scaffolding protein originally identified at the neuronal postsynaptic density, is expressed in podocytes in vivo and in vitro and plays an important role in albumin endocytosis in podocytes. Knockdown of Shank2 in cultured human podocytes decreased albumin uptake, but the decrease was not statistically significant likely due to residual Shank2 still present in the knockdown podocytes. Complete knockout of Shank2 in podocytes significantly diminished albumin uptake in vitro. Shank2 knockout mice develop proteinuria by 8 weeks of age. To examine albumin handling in vivo in wild-type and Shank2 knockout mice we used multiphoton intravital imaging. While FITC-labeled albumin was rapidly seen in the renal tubules of wild-type mice after injection, little albumin was seen in the tubules of Shank2 knockout mice indicating dysregulated renal albumin trafficking in the Shank2 knockouts. We have previously found that caveolin-1 is required for albumin endocytosis in cultured podocytes. Shank2 knockout mice had significantly decreased expression and altered localization of caveolin-1 in podocytes suggesting that disruption of albumin endocytosis in Shank2 knockouts is mediated via caveolin-1. In summary, we have identified Shank2 as another component of the albumin endocytic pathway in podocytes. PMID:26333830

  5. A Hypothesis for Using Pathway Genetic Load Analysis for Understanding Complex Outcomes in Bilirubin Encephalopathy.

    PubMed

    Riordan, Sean M; Bittel, Douglas C; Le Pichon, Jean-Baptiste; Gazzin, Silvia; Tiribelli, Claudio; Watchko, Jon F; Wennberg, Richard P; Shapiro, Steven M

    2016-01-01

    Genetic-based susceptibility to bilirubin neurotoxicity and chronic bilirubin encephalopathy (kernicterus) is still poorly understood. Neonatal jaundice affects 60-80% of newborns, and considerable effort goes into preventing this relatively benign condition from escalating into the development of kernicterus making the incidence of this potentially devastating condition very rare in more developed countries. The current understanding of the genetic background of kernicterus is largely comprised of mutations related to alterations of bilirubin production, elimination, or both. Less is known about mutations that may predispose or protect against CNS bilirubin neurotoxicity. The lack of a monogenetic source for this risk of bilirubin neurotoxicity suggests that disease progression is dependent upon an overall decrease in the functionality of one or more essential genetically controlled metabolic pathways. In other words, a "load" is placed on key pathways in the form of multiple genetic variants that combine to create a vulnerable phenotype. The idea of epistatic interactions creating a pathway genetic load (PGL) that affects the response to a specific insult has been previously reported as a PGL score. We hypothesize that the PGL score can be used to investigate whether increased susceptibility to bilirubin-induced CNS damage in neonates is due to a mutational load being placed on key genetic pathways important to the central nervous system's response to bilirubin neurotoxicity. We propose a modification of the PGL score method that replaces the use of a canonical pathway with custom gene lists organized into three tiers with descending levels of evidence combined with the utilization of single nucleotide polymorphism (SNP) causality prediction methods. The PGL score has the potential to explain the genetic background of complex bilirubin induced neurological disorders (BIND) such as kernicterus and could be the key to understanding ranges of outcome severity in

  6. A Novel Perspective on the Biology of Bilirubin in Health and Disease.

    PubMed

    Gazzin, Silvia; Vitek, Libor; Watchko, Jon; Shapiro, Steven M; Tiribelli, Claudio

    2016-09-01

    Unconjugated bilirubin (UCB) is known to be one of the most potent endogenous antioxidant substances. While hyperbilirubinemia has long been recognized as an ominous sign of liver dysfunction, recent data strongly indicate that mildly elevated bilirubin (BLB) levels can be protective against an array of diseases associated with increased oxidative stress. These clinical observations are supported by new discoveries relating to the role of BLB in immunosuppression and inhibition of protein phosphorylation, resulting in the modulation of intracellular signaling pathways in vascular biology and cancer, among others. Collectively, the evidence suggests that targeting BLB metabolism could be considered a potential therapeutic approach to ameliorate a variety of conditions. PMID:27515064

  7. Oxygen biosensor based on bilirubin oxidase immobilized on a nanostructured gold electrode.

    PubMed

    Pita, Marcos; Gutierrez-Sanchez, Cristina; Toscano, Miguel D; Shleev, Sergey; De Lacey, Antonio L

    2013-12-01

    Gold disk electrodes modified with gold nanoparticles have been used as a scaffold for the covalent immobilization of bilirubin oxidase. The nanostructured bioelectrodes were tested as mediator-less biosensors for oxygen in a buffer that mimics the content and the composition of human physiological fluids. Chronoamperometry measurements showed a detection limit towards oxygen of 6 ± 1 μM with a linear range of 6-300 μM, i.e. exceeding usual physiological ranges of oxygen in human tissues and fluids. The biosensor presented is the first ever-reported oxygen amperometric biosensor based on direct electron transfer of bilirubin oxidase. PMID:23973738

  8. A Hypothesis for Using Pathway Genetic Load Analysis for Understanding Complex Outcomes in Bilirubin Encephalopathy

    PubMed Central

    Riordan, Sean M.; Bittel, Douglas C.; Le Pichon, Jean-Baptiste; Gazzin, Silvia; Tiribelli, Claudio; Watchko, Jon F.; Wennberg, Richard P.; Shapiro, Steven M.

    2016-01-01

    Genetic-based susceptibility to bilirubin neurotoxicity and chronic bilirubin encephalopathy (kernicterus) is still poorly understood. Neonatal jaundice affects 60–80% of newborns, and considerable effort goes into preventing this relatively benign condition from escalating into the development of kernicterus making the incidence of this potentially devastating condition very rare in more developed countries. The current understanding of the genetic background of kernicterus is largely comprised of mutations related to alterations of bilirubin production, elimination, or both. Less is known about mutations that may predispose or protect against CNS bilirubin neurotoxicity. The lack of a monogenetic source for this risk of bilirubin neurotoxicity suggests that disease progression is dependent upon an overall decrease in the functionality of one or more essential genetically controlled metabolic pathways. In other words, a “load” is placed on key pathways in the form of multiple genetic variants that combine to create a vulnerable phenotype. The idea of epistatic interactions creating a pathway genetic load (PGL) that affects the response to a specific insult has been previously reported as a PGL score. We hypothesize that the PGL score can be used to investigate whether increased susceptibility to bilirubin-induced CNS damage in neonates is due to a mutational load being placed on key genetic pathways important to the central nervous system's response to bilirubin neurotoxicity. We propose a modification of the PGL score method that replaces the use of a canonical pathway with custom gene lists organized into three tiers with descending levels of evidence combined with the utilization of single nucleotide polymorphism (SNP) causality prediction methods. The PGL score has the potential to explain the genetic background of complex bilirubin induced neurological disorders (BIND) such as kernicterus and could be the key to understanding ranges of outcome severity

  9. Age-dependent pattern of cerebellar susceptibility to bilirubin neurotoxicity in vivo in mice

    PubMed Central

    Bortolussi, Giulia; Baj, Gabriele; Vodret, Simone; Viviani, Giulia; Bittolo, Tamara; Muro, Andrés F.

    2014-01-01

    Neonatal jaundice is caused by high levels of unconjugated bilirubin. It is usually a temporary condition caused by delayed induction of UGT1A1, which conjugates bilirubin in the liver. To reduce bilirubin levels, affected babies are exposed to phototherapy (PT), which converts toxic bilirubin into water-soluble photoisomers that are readily excreted out. However, in some cases uncontrolled hyperbilirubinemia leads to neurotoxicity. To study the mechanisms of bilirubin-induced neurological damage (BIND) in vivo, we generated a mouse model lacking the Ugt1a1 protein and, consequently, mutant mice developed jaundice as early as 36 hours after birth. The mutation was transferred into two genetic backgrounds (C57BL/6 and FVB/NJ). We exposed mutant mice to PT for different periods and analyzed the resulting phenotypes from the molecular, histological and behavioral points of view. Severity of BIND was associated with genetic background, with 50% survival of C57BL/6‑Ugt1−/− mutant mice at postnatal day 5 (P5), and of FVB/NJ-Ugt1−/− mice at P11. Life-long exposure to PT prevented cerebellar architecture alterations and rescued neuronal damage in FVB/NJ-Ugt1−/− but not in C57BL/6-Ugt1−/− mice. Survival of FVB/NJ-Ugt1−/− mice was directly related to the extent of PT treatment. PT treatment of FVB/NJ-Ugt1−/− mice from P0 to P8 did not prevent bilirubin-induced reduction in dendritic arborization and spine density of Purkinje cells. Moreover, PT treatment from P8 to P20 did not rescue BIND accumulated up to P8. However, PT treatment administered in the time-window P0–P15 was sufficient to obtain full rescue of cerebellar damage and motor impairment in FVB/NJ-Ugt1−/− mice. The possibility to modulate the severity of the phenotype by PT makes FVB/NJ-Ugt1−/− mice an excellent and versatile model to study bilirubin neurotoxicity, the role of modifier genes, alternative therapies and cerebellar development during high bilirubin conditions. PMID

  10. Recombinant albumin monolayers on latex particles.

    PubMed

    Sofińska, Kamila; Adamczyk, Zbigniew; Kujda, Marta; Nattich-Rak, Małgorzata

    2014-01-14

    The adsorption of recombinant human serum albumin (rHSA) on negatively charged polystyrene latex micro-particles was studied at pH 3.5 and the NaCl concentration range of 10(-3) to 0.15 M. The electrophoretic mobility of latex monotonically increased with the albumin concentration in the suspension. The coverage of adsorbed albumin was quantitatively determined using the depletion method, where the residual protein concentration was determined by electrokinetic measurements and AFM imaging. It was shown that albumin adsorption was irreversible. Its maximum coverage on latex varied between 0.7 mg m(-2) for 10(-3) M NaCl to 1.3 mg m(-2) for 0.15 M NaCl. The latter value matches the maximum coverage previously determined for human serum albumin on mica using the streaming potential method. The increase in the maximum coverage was interpreted in terms of reduced electrostatic repulsion among adsorbed molecules. These facts confirm that albumin adsorption at pH 3.5 is governed by electrostatic interactions and proceeds analogously to colloid particle deposition. The stability of albumin monolayers was measured in additional experiments where changes in the latex electrophoretic mobility and the concentration of free albumin in solutions were monitored over prolonged time periods. Based on these experimental data, a robust procedure of preparing albumin monolayers on latex particles of well-controlled coverage and molecule distribution was proposed. PMID:24354916

  11. Evaluation and comparison of postoperative levels of serum bilirubin, serum transaminases and alkaline phosphatase in laparoscopic cholecystectomy versus open cholecystectomy

    PubMed Central

    Singal, Rajinder Pal; Sandhu, Karamjot; Singh, Bir; Bhatia, Gaurav; Khatri, Abhishek; Sharma, Bhanu Pratap

    2015-01-01

    Background Laparoscopic cholecystectomy (LC) requires the creation of a pneumoperitoneum via insufflations of carbon dioxide; resulting in increased partial pressure of carbon dioxide (CO2) and intraperitoneal pressure which leads to the changes in pulmonary function and hemodynamic measurements. Hypercarbia leads to visceral organ ischemia including liver and venous stasis/thromboembolism or both due to impaired flow. The present study has been undertaken to see the changes in liver function tests (LFTs) after laparoscopic/open cholecystectomy (OC), the incidences of such change, their relation to age, sex, duration of surgery and to know the clinical significances of such disturbances. Aims and objectives To compare and correlate the serum level of bilirubin, alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) in patients who underwent LC to those who underwent OC. Materials and methods The present study was conducted in the Department of Surgery at MMIMSR, MM University, Mullana, Ambala. A total number of 200 patients diagnosed as cholelithiasis were included in the study from May 2012 to May 2014. These cases were randomly divided into two groups (A and B) consisting of 100 cases each. LC was performed in group A patients and OC was done in group B patients. Three blood samples were taken: (I) pre-operatively; (II) after 24 hours of surgery; and (III) after 72 hours of surgery for comparison of the enzyme level alterations. Results In LC patients, there were rise in the levels of serum bilirubin, AST and ALT after 24 hrs of surgery from the preoperative value and then again fall was noted (near to normal value) after 72 hrs of surgery except in that of ALP. ALP levels showed slight fall after 24 hrs of surgery and then slight rise after 72 hrs which was within the normal limit. Whereas in OC patients, there were slight variations in the liver enzymes (which were within the normal range). Conclusions Transient elevation of serum

  12. The Negative Relationship between Bilirubin Level and Diabetic Retinopathy: A Meta-Analysis

    PubMed Central

    Wu, Xiaomei; Ning, Kang; Jiang, Feng; Zhang, Lu

    2016-01-01

    Objectives Findings on the relationship between total bilirubin level (TBL) and diabetic retinopathy (DR) are inconsistent. Thus, we carried out a meta-analysis to investigate the relationship between TBL and the risk of DR. Methods Relevant studies were selected from six databases up to 31 May 2016 using a search strategy. The relevant data were extracted from the included studies according to the inclusion and exclusion criteria, and the mean value with standard errors or odds ratio (OR) with 95% confidence intervals (CIs) were calculated. We compared TBL in patients with DR with that in patients with diabetes but without retinopathy (NDR), and analyzed the dose-response relationship between TBL and the risk of DR. Results Twenty-four studies were selected in this meta-analysis. Twenty studies were included to calculate the pooled SMD, and the results showed that TBL in the DR group was lower than that in the NDR group (SMD: –0.52, 95% CI: –0.67, –0.38). Nine studies were included to calculate the pooled ORs, and the results showed that there was a significant negative relationship between TBL and the risk of DR (OR: 0.19, 95% CI: 0.14, 0.25). Six studies were included to investigate the dose-response relationship between TBL and the risk of DR, and we found a nonlinear relationship between TBL and the risk of DR. The results of our meta-analysis were found to be reliable using subgroup and sensitivity analyses. Conclusions The results of our meta-analysis indicate that higher TBL may be protective against DR in subjects with diabetes, and TBL could be used as a biomarker to predict the risk of DR. PMID:27571522

  13. Bilirubin, platelet activation and heart disease: a missing link to cardiovascular protection in Gilbert's syndrome?

    PubMed

    Kundur, Avinash R; Singh, Indu; Bulmer, Andrew C

    2015-03-01

    Gilbert's syndrome (GS) is a relatively common condition, inducing a benign, non-hemolytic, unconjugated hyperbilirubinemia. Gilbert's Syndrome is associated with mutation in the Uridine Glucuronosyl Transferase 1A1 (UGT1A1) gene promoter, reducing UGT1A1 activity, which normally conjugates bilirubin allowing its elimination from the blood. Individuals with GS demonstrate mildly elevated plasma antioxidant capacity caused by elevated levels of unconjugated bilirubin (UCB), reduced thiols and glutathione. Interestingly, the development of, and risk of mortality from, cardiovascular disease is remarkably reduced in GS individuals. An explanation for this protection may be explained by bilirubin's ability to inhibit multiple processes that induce platelet hyper-reactivity and thrombosis, thus far under-appreciated in the literature. Reactive oxygen species are produced continuously via metabolic processes and have the potential to oxidatively modify proteins and lipids within cell membranes, which may encourage the development of thrombosis and CVDs. Oxidative stress induced platelet hyper-reactivity significantly increases the risk of thrombosis, which can potentially lead to tissue infarction. Here, we discuss the possible mechanisms by which increased antioxidant status might influence platelet function and link this to cardiovascular protection in GS. In summary, this is the first article to discuss the possible role of bilirubin as an anti-thrombotic agent, which inhibits platelet activation and potentially, organ infarction, which could contribute to the reduced mortality rate in mildly hyperbilirbinemic individuals. PMID:25576848

  14. 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...

  15. 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...

  16. 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...

  17. 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...

  18. 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...

  19. Comparison of Calcium Phosphate and Zinc Oxide Nanoparticles as Dermal Penetration Enhancers for Albumin

    PubMed Central

    Shokri, Narges; Javar, H. A.

    2015-01-01

    quicker. Maximum cumulative (total) permeated albumin in presence of zinc oxide nanoparticles was obtained at time of 1.5 h, which was 40.2±3.6 mg, while in presence of calcium phosphate nanoparticles, it was obtained at 1 h, which was 33.8±5.5 mg. Skin distribution of the nanoparticles and albumin confirmed the above profiles. PMID:26997697

  20. Comparison of Calcium Phosphate and Zinc Oxide Nanoparticles as Dermal Penetration Enhancers for Albumin.

    PubMed

    Shokri, Narges; Javar, H A

    2015-01-01

    quicker. Maximum cumulative (total) permeated albumin in presence of zinc oxide nanoparticles was obtained at time of 1.5 h, which was 40.2±3.6 mg, while in presence of calcium phosphate nanoparticles, it was obtained at 1 h, which was 33.8±5.5 mg. Skin distribution of the nanoparticles and albumin confirmed the above profiles. PMID:26997697

  1. Glycated Serum Albumin and AGE Receptors.

    PubMed

    Vetter, Stefan W

    2015-01-01

    In vivo modification of proteins by molecules with reactive carbonyl groups leads to intermediate and advanced glycation end products (AGE). Glucose is a significant glycation reagent due to its high physiological concentration and poorly controlled diabetics show increased albumin glycation. Increased levels of glycated and AGE-modified albumin have been linked to diabetic complications, neurodegeneration, and vascular disease. This review discusses glycated albumin formation, structural consequences of albumin glycation on drug binding, removal of circulating AGE by several scavenger receptors, as well as AGE-induced proinflammatory signaling through activation of the receptor for AGE. Analytical methods for quantitative detection of protein glycation and AGE formation are compared. Finally, the use of glycated albumin as a novel clinical marker to monitor glycemic control is discussed and compared to glycated hemoglobin (HbA1c) as long-term indicator of glycemic status. PMID:26471084

  2. Selective nonenzymatic bilirubin detection in blood samples using a Nafion/Mn-Cu sensor.

    PubMed

    Noh, Hui-Bog; Won, Mi-Sook; Shim, Yoon-Bo

    2014-11-15

    The specific detection of biological organics without the use of an enzyme is challenging, and it is crucial for analytical and clinical chemistry. We report specific nonenzymatic bilirubin detection through the catalytic oxidation of bilirubin molecule on the Nafion/Mn-Cu surface. The catalytic ability, true surface area, morphology, crystallinity, composition, and oxidation state of the sensor surface were assessed using voltammetry, coulometry, XPS, XRD, Brunauer-Emmett-Teller (BET), SEM, EDXS, and TOF-SIMS experiments. The results showed that the surface was composed of microporous Mn-Cu bimetallic crystal in flake shape with a large BET surface area (3.635 m(2)g(-1)), where the surface area and crystallinity mainly affected the sensor performance. Product analysis of the catalytic reaction on the sensor probe revealed a specific two-electron oxidation of dipyrromethane moiety to dipyrromethene in the bilirubin molecule. Experimental variables affecting the analysis of bilirubin were optimized in terms of probe composition, temperature, pH, and potential. At the optimized condition, the dynamic range was between 1.2 μM and 0.42 mM, which yielded the equation of ΔI (μA)=(1.03 ± 0.72)+(457.0 ± 4.03) [C] (mM) with 0.999 of correlation coefficient, and the detection limit was 25.0 ± 1.8 nM (n=5, k=3). The stability test, interference effects, and analysis of real clinical samples, human whole blood and certified serum samples were demonstrated to confirm the reliability of the proposed bilirubin sensor. PMID:24953842

  3. The Role of Bilirubin in Diabetes, Metabolic Syndrome, and Cardiovascular Diseases

    PubMed Central

    Vítek, Libor

    2012-01-01

    Bilirubin belongs to a phylogenetically old superfamily of tetrapyrrolic compounds, which have multiple biological functions. Although for decades bilirubin was believed to be only a waste product of the heme catabolic pathway at best, and a potentially toxic compound at worst; recent data has convincingly demonstrated that mildly elevated serum bilirubin levels are strongly associated with a lower prevalence of oxidative stress-mediated diseases. Indeed, serum bilirubin has been consistently shown to be negatively correlated to cardiovascular diseases (CVD), as well as to CVD-related diseases and risk factors such as arterial hypertension, diabetes mellitus, metabolic syndrome, and obesity. In addition, the clinical data are strongly supported by evidence arising from both in vitro and in vivo experimental studies. This data not only shows the protective effects of bilirubin per se; but additionally, of other products of the heme catabolic pathway such as biliverdin and carbon monoxide, as well as its key enzymes (heme oxygenase and biliverdin reductase); thus, further underlining the biological impacts of this pathway. In this review, detailed information on the experimental and clinical evidence between the heme catabolic pathway and CVD, and those related diseases such as diabetes, metabolic syndrome, and obesity is provided. All of these pathological conditions represent an important threat to human civilization, being the major killers in developed countries, with a steadily increasing prevalence. Thus, it is extremely important to search for novel markers of these diseases, as well as for novel therapeutic modalities to reverse this unfavorable situation. The heme catabolic pathway seems to fulfill the criteria for both diagnostic purposes as well as for potential therapeutical interventions. PMID:22493581

  4. Studies on sodium-borohydride-reducible hexose in glucosyl-albumin.

    PubMed

    Sharma, K K; Rai, K B; Pattabiraman, T N

    1983-08-01

    Glucosylated albumin of human serum isolated by dye-ligand chromatography on blue Sepharose, was not found to be completely reducible by sodium borohydride. The percentage reducible hexose as judged by phenol-sulphuric acid reaction was in the range of 49.7 +/- 12.8 in control subjects (n = 24) and 53.8 +/- 14.2 in diabetics (n = 50). Increase in the level of total hexose bound to albumin and reducible hexose were equally significant in diabetes (P less than 0.001). Sodium chloride gradient elution during chromatography on blue Sepharose showed that glucosylated albumin had lesser affinity than the native protein to the matrix. It is proposed that an addition product between hexose and albumin is formed during nonenzymatic reaction and this adduct is fairly stable and is not reducible by sodium borohydride. PMID:6626188

  5. Purification, identification and preliminary crystallographic studies of a 2S albumin seed protein from Lens culinaris

    SciTech Connect

    Gupta, Pankaj; Gaur, Vineet; Salunke, Dinakar M.

    2008-08-01

    A 2S albumin from L. culinaris was purified and crystallized and preliminary crystallographic studies were carried out. Lens culinaris (lentil) is a widely consumed high-protein-content leguminous crop. A 2S albumin protein (26.5 kDa) has been identified using NH{sub 2}-terminal sequencing from a 90% ammonium sulfate saturation fraction of total L. culinaris seed protein extract. The NH{sub 2}-terminal sequence shows very high homology to PA2, an allergy-related protein from Pisum sativum. The 2S albumin protein was purified using a combination of size-exclusion and ion-exchange chromatography. Crystals of the 2S seed albumin obtained using the hanging-drop vapour-diffusion method diffracted to 2.5 Å resolution and were indexed in space group P4{sub 1} (or P4{sub 3}), with unit-cell parameters a = b = 78.6, c = 135.2 Å.

  6. Oxidative changes in the blood and serum albumin differentiate rats with monoarthritis and polyarthritis.

    PubMed

    Bracht, Adelar; Silveira, Sandra Silva; Castro-Ghizoni, Cristiane Vizioli; Sá-Nakanishi, Anacharis Babeto; Oliveira, Márcia Rosângela Neves; Bersani-Amado, Ciomar Aparecida; Peralta, Rosane Marina; Comar, Jurandir Fernando

    2016-01-01

    Adjuvant arthritis in rats, as rheumatoid arthritis in humans, may be of greater or lesser severity, namely polyarthritis and monoarthritis, respectively. The present study was planned to evaluate the oxidative changes in the blood and specifically in the serum albumin of rats with adjuvant-induced mono- and poly-arthritis. Total antioxidant capacity, thiols, carbonyl groups, albumin, uric acid and ascorbic acid were measured in the total serum. The specific oxidative status of albumin was also measured after separation by affinity chromatography. All serum oxidative parameters were close to normal in monoarthritic rats with the exception of the ascorbic acid concentration, which was 23 % lower, and albumin carbonyl groups, which were 64 % higher. Many modifications were found in polyarthritic rats, specially the ascorbic acid concentration (35 % lower) and albumin carbonyl groups (102 % higher). The results revealed that the levels of ascorbic acid in the serum and carbonyl groups in the albumin molecule can be regarded as indicators of the severity of arthritis since they were modified by both monoarthritis and polyarthritis, but to different degrees. PMID:26835218

  7. The effect of bilirubin on the excitability of mitral cells in the olfactory bulb of the rat

    PubMed Central

    Chen, Xiao-Juan; Zhou, Hui-Qun; Ye, Hai-bo; Li, Chun-Yan; Zhang, Wei-Tian

    2016-01-01

    Olfactory dysfunction is a common clinical phenomenon observed in various liver diseases. Previous studies have shown a correlation between smell disorders and bilirubin levels in patients with hepatic diseases. Bilirubin is a well-known neurotoxin; however, its effect on neurons in the main olfactory bulb (MOB), the first relay in the olfactory system, has not been examined. We investigated the effect of bilirubin (>3 μM) on mitral cells (MCs), the principal output neurons of the MOB. Bilirubin increased the frequency of spontaneous firing and the frequency but not the amplitude of spontaneous excitatory postsynaptic currents (sEPSCs). TTX completely blocked sEPSCs in almost all of the cells tested. Bilirubin activity was partially blocked by N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepro pionic acid (AMPA) receptor antagonists. Furthermore, we found that bilirubin increased the frequency of intrinsic firing independent of synaptic transmission in MCs. Our findings suggest that bilirubin enhances glutamatergic transmission and strengthens intrinsic firing independent of synaptic transmission, all of which cause hyperexcitability in MCs. Our findings provide the basis for further investigation into the mechanisms underlying olfactory dysfunction that are often observed in patients with severe liver disease. PMID:27611599

  8. The effect of bilirubin on the excitability of mitral cells in the olfactory bulb of the rat.

    PubMed

    Chen, Xiao-Juan; Zhou, Hui-Qun; Ye, Hai-Bo; Li, Chun-Yan; Zhang, Wei-Tian

    2016-01-01

    Olfactory dysfunction is a common clinical phenomenon observed in various liver diseases. Previous studies have shown a correlation between smell disorders and bilirubin levels in patients with hepatic diseases. Bilirubin is a well-known neurotoxin; however, its effect on neurons in the main olfactory bulb (MOB), the first relay in the olfactory system, has not been examined. We investigated the effect of bilirubin (>3 μM) on mitral cells (MCs), the principal output neurons of the MOB. Bilirubin increased the frequency of spontaneous firing and the frequency but not the amplitude of spontaneous excitatory postsynaptic currents (sEPSCs). TTX completely blocked sEPSCs in almost all of the cells tested. Bilirubin activity was partially blocked by N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepro pionic acid (AMPA) receptor antagonists. Furthermore, we found that bilirubin increased the frequency of intrinsic firing independent of synaptic transmission in MCs. Our findings suggest that bilirubin enhances glutamatergic transmission and strengthens intrinsic firing independent of synaptic transmission, all of which cause hyperexcitability in MCs. Our findings provide the basis for further investigation into the mechanisms underlying olfactory dysfunction that are often observed in patients with severe liver disease. PMID:27611599

  9. Role of brain cytochrome P450 mono-oxygenases in bilirubin oxidation-specific induction and activity.

    PubMed

    Gambaro, Sabrina E; Robert, Maria C; Tiribelli, Claudio; Gazzin, Silvia

    2016-02-01

    In the Crigler-Najjar type I syndrome, the genetic absence of efficient hepatic glucuronidation of unconjugated bilirubin (UCB) by the uridine 5'-diphospho-glucuronosyltransferase1A1 (UGT1A1) enzyme produces the rise of UCB level in blood. Its entry to central nervous system could generate toxicity and neurological damage, and even death. In the past years, a compensatory mechanism to liver glucuronidation has been indicated in the hepatic cytochromes P450 enzymes (Cyps) which are able to oxidize bilirubin. Cyps are expressed also in the central nervous system, the target of bilirubin toxicity, thus making them theoretically important to confer a protective activity toward bilirubin accumulation and neurotoxicity. We therefore investigated the functional induction (mRNA, EROD/MROD) and the ability to oxidize bilirubin of Cyp1A1, 1A2, and 2A3 in primary astrocytes cultures obtained from two rat brain region (cortex: Cx and cerebellum: Cll). We observed that Cyp1A1 was the Cyp isoform more easily induced by beta-naphtoflavone (βNF) in both Cx and Cll astrocytes, but oxidized bilirubin only after uncoupling by 3, 4,3',4'-tetrachlorobiphenyl (TCB). On the contrary, Cyp1A2 was the most active Cyp in bilirubin clearance without uncoupling, but its induction was confined only in Cx cells. Brain Cyp2A3 was not inducible. In conclusion, the exposure of astrocytes to βNF plus TCB significantly enhanced Cyp1A1 mediating bilirubin clearance, improving cell viability in both regions. These results may be a relevant groundwork for the manipulation of brain Cyps as a therapeutic approach in reducing bilirubin-induced neurological damage. PMID:25370011

  10. Bilirubin prevents acute DSS-induced colitis by inhibiting leukocyte infiltration and suppressing upregulation of inducible nitric oxide synthase.

    PubMed

    Zucker, Stephen D; Vogel, Megan E; Kindel, Tammy L; Smith, Darcey L H; Idelman, Gila; Avissar, Uri; Kakarlapudi, Ganesh; Masnovi, Michelle E

    2015-11-15

    Bilirubin is thought to exert anti-inflammatory effects by inhibiting vascular cell adhesion molecule-1 (VCAM-1)-dependent leukocyte migration and by suppressing the expression of inducible nitric oxide synthase (iNOS). As VCAM-1 and iNOS are important mediators of tissue injury in the dextran sodium sulfate (DSS) murine model of inflammatory colitis, we examined whether bilirubin prevents colonic injury in DSS-treated mice. Male C57BL/6 mice were administered 2.5% DSS in the drinking water for 7 days, while simultaneously receiving intraperitoneal injections of bilirubin (30 mg/kg) or potassium phosphate vehicle. Disease activity was monitored, peripheral blood counts and serum nitrate levels were determined, and intestinal specimens were analyzed for histological injury, leukocyte infiltration, and iNOS expression. The effect of bilirubin on IL-5 production by HSB-2 cells and on Jurkat cell transendothelial migration also was determined. DSS-treated mice that simultaneously received bilirubin lost less body weight, had lower serum nitrate levels, and exhibited reduced disease severity than vehicle-treated animals. Concordantly, histopathological analyses revealed that bilirubin-treated mice manifested significantly less colonic injury, including reduced infiltration of eosinophils, lymphocytes, and monocytes, and diminished iNOS expression. Bilirubin administration also was associated with decreased eosinophil and monocyte infiltration into the small intestine, with a corresponding increase in peripheral blood eosinophilia. Bilirubin prevented Jurkat migration but did not alter IL-5 production. In conclusion, bilirubin prevents DSS-induced colitis by inhibiting the migration of leukocytes across the vascular endothelium and by suppressing iNOS expression. PMID:26381705

  11. Inducible bilirubin oxidase: A novel function for the mouse cytochrome P450 2A5

    SciTech Connect

    Abu-Bakar, A'edah; Arthur, Dionne Maioha; Aganovic, Simona; Ng, Jack C.; Lang, Matti A.

    2011-11-15

    We have previously shown that bilirubin (BR), a breakdown product of haem, is a strong inhibitor and a high affinity substrate of the mouse cytochrome P450 2A5 (CYP2A5). The antioxidant BR, which is cytotoxic at high concentrations, is potentially useful in cellular protection against oxygen radicals if its intracellular levels can be strictly controlled. The mechanisms that regulate cellular BR levels are still obscure. In this paper we provide preliminary evidence for a novel function of CYP2A5 as hepatic 'BR oxidase'. A high-performance liquid chromatography/electrospray ionisation mass spectrometry screening showed that recombinant yeast microsomes expressing the CYP2A5 oxidise BR to biliverdin, as the main metabolite, and to three other smaller products with m/z values of 301, 315 and 333. The metabolic profile is significantly different from that of chemical oxidation of BR. In chemical oxidation the smaller products were the main metabolites. This suggests that the enzymatic reaction is selective, towards biliverdin production. Bilirubin treatment of primary hepatocytes increased the CYP2A5 protein and activity levels with no effect on the corresponding mRNA. Co-treatment with cycloheximide (CHX), a protein synthesis inhibitor, resulted in increased half-life of the CYP2A5 compared to cells treated only with CHX. Collectively, the observations suggest that the CYP2A5 is potentially an inducible 'BR oxidase' where BR may accelerate its own metabolism through stabilization of the CYP2A5 protein. It is possible that this metabolic pathway is potentially part of the machinery controlling intracellular BR levels in transient oxidative stress situations, in which high amounts of BR are produced. -- Highlights: Black-Right-Pointing-Pointer CYP2A5 metabolizes bilirubin to biliverdin and dipyrroles. Black-Right-Pointing-Pointer Bilirubin increased the hepatic CYP2A5 protein and activity levels. Black-Right-Pointing-Pointer Bilirubin does not change the hepatic CYP2A5

  12. Interaction of bilirubin and indocyanine green with the binding and conjugation of sulfobromophthalein by rat liver cytosol proteins.

    PubMed

    Davis, D R; Yeary, R A

    1980-02-01

    The interaction of bilirubin and indocyanine green with sulfobromophthalein (BSP) binding and conjugation by rat liver cytosol proteins was studied. BSP bound to cytosol proteins X, ligandin and Z and the BSP-glutathione conjugate were isolated by sephadex gel chromatography. Neither bilirubin nor indocyanine green affected the binding of BSP to ligandin and Z protein. However, indocyanine green did significantly reduce BSP conjugation in both in vitro and in vivo experiments. Diethyl maleate significantly reduced liver glutathione levels and BSP conjugation. It is suggested that indocyanine gree competitively binds at the ligandin catalytic site whereas the primary binding site for bilirubin is probably a noncatalytic site. PMID:7367753

  13. Enhancements of the production of bilirubin and the expression of β-globin by carbon monoxide during erythroid differentiation.

    PubMed

    Mu, Anfeng; Li, Ming; Tanaka, Masakazu; Adachi, Yasushi; Tai, Tran Tien; Liem, Pham Hieu; Izawa, Shingo; Furuyama, Kazumichi; Taketani, Shigeru

    2016-05-01

    Heme is degraded by heme oxygenase to form iron, carbon monoxide (CO), and biliverdin. However, information about the catabolism of heme in erythroid cells is limited. In this study, we showed the production and export of bilirubin in murine erythroleukemia (MEL) cells. The production of bilirubin by MEL cells was enhanced when heme synthesis was induced. When mouse bone marrow cells were induced with erythropoietin to differentiate into erythroid cells, the synthesis of bilirubin increased. The expression of β-globin was enhanced by CO at the transcriptional level. These results indicate that constant production of CO from heme regulates erythropoiesis. PMID:27087140

  14. 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. PMID:26055641

  15. 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.

  16. Fully Oriented Bilirubin Oxidase on Porphyrin-Functionalized Carbon Nanotube Electrodes for Electrocatalytic Oxygen Reduction.

    PubMed

    Lalaoui, Noémie; Le Goff, Alan; Holzinger, Michael; Cosnier, Serge

    2015-11-16

    The efficient immobilization and orientation of bilirubin oxidase from Myrothecium verrucaria on multi-walled carbon nanotube electrodes by using π-stacked porphyrins as a direct electron-transfer promoter is reported. By comparing the use of different types of porphyrin, the rational effect of the porphyrin structure on both the immobilization and orientation of the enzyme is demonstrated. The best performances were obtained for protoporphyrin IX, which is the natural precursor of bilirubin. These electrodes exhibit full orientation of the enzyme, as confirmed by the observable non-catalytic redox system corresponding to the T1 copper center associated with pure Nernstian electrocatalytic behavior with high catalytic currents of almost 5 mA cm(-2) at neutral pH. PMID:26449635

  17. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) increases bilirubin formation but hampers quantitative hepatic conversion of biliverdin to bilirubin in rats with wild-type AH receptor.

    PubMed

    Niittynen, Marjo; Simanainen, Ulla; Pohjanvirta, Raimo; Sankari, Satu; Tuomisto, Jouni T

    2014-06-01

    In haem degradation, haem oxygenase-1 (HO-1) first cleaves haem to biliverdin, which is reduced to bilirubin by biliverdin IXα reductase (BVR-A). The environmental pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) causes hepatic accumulation of biliverdin in moderately TCDD-resistant line B (Kuopio) rats. Using line B and two TCDD-sensitive rat strains, the present study set out to probe the dose-response and biochemical mechanisms of this accumulation. At 28 days after exposure to 3-300 μg/kg TCDD in line B rats, already the lowest dose of TCDD tested, 3 μg/kg, affected serum bilirubin conjugates, and after doses ≥100 μg/kg, the liver content of bilirubin, biliverdin and their conjugates (collectively 'bile pigments') as well as HO-1 was elevated. BVR-A activity and serum bile acids were increased only by the doses of 100 and 300 μg/kg TCDD, respectively. Biliverdin conjugates correlated best with biliverdin suggesting it to be their immediate precursor. TCDD (100 μg/kg, 10 days) increased hepatic bilirubin and biliverdin levels also in TCDD-sensitive Long-Evans (Turku/AB; L-E) rats. Hepatic bilirubin and bile acids, but not biliverdin, were increased in feed-restricted L-E control rats. In TCDD-sensitive line C (Kuopio) rats, 10 μg/kg of TCDD increased the body-weight-normalized biliary excretion of bilirubin. Altogether, the results suggest that at acutely toxic doses, TCDD induces the formation of bilirubin in rats. However, concurrently, TCDD seems to hamper the quantitative conversion of biliverdin to bilirubin in line B and L-E rats' liver. Biliverdin conjugates are most likely formed as secondary products of biliverdin. PMID:24418412

  18. Albumin quotient, IgG concentration, and IgG index determinations in cerebrospinal fluid of neonatal foals.

    PubMed

    Andrews, F M; Geiser, D R; Sommardahl, C S; Green, E M; Provenza, M

    1994-06-01

    Total protein (TP), albumin, and IgG concentrations were measured in CSF from the atlanto-occipital (AO) and lumbosacral (LS) sites and in serum of 15 clinically normal neonatal foals < or = 10 days old (mean, 7.0 days). The albumin quotient (AQ; CSF albumin/serum albumin x 100) and IgG index ([CSF IgG/serum IgG] x [serum albumin/CSF albumin]), indicators of blood-brain barrier permeability and intrathecal IgG production, respectively, were then calculated. Mean +/- SD values obtained from the foals of this study were: serum albumin, 2,900 +/- 240 mg/dl; serum IgG, 1,325 +/- 686 mg/dl; AO CSF total protein (TP), 82.8 +/- 19.2 mg/dl; LS CSF TP, 83.6 +/- 16.1 mg/dl; AO CSF albumin, 52.0 +/- 8.6 mg/dl; LS CSF albumin, 53.8 +/- 15.7 mg/dl; AO CSF IgG, 10.2 +/- 5.5 mg/dl; LS CSF IgG, 9.9 +/- 5.7 mg/dl; AO AQ, 1.86 +/- 0.29; LS AQ, 1.85 +/- 0.51, AO IgG index, 0.52 +/- 0.28; and LS IgG index, 0.48 +/- 0.27. Significant difference between values for the AO and LS sites was not found. A CSF albumin concentration > 85.2 mg/dl or AQ > 2.4, as determined by mean +/- 2 SD, may indicate increased blood-brain barrier permeability. An IgG index value > 1.0 may indicate intrathecal IgG production. Values obtained for foals of this study should serve as baseline for comparison in the evaluation of blood-brain barrier permeability and intrathecal IgG production in neonatal foals with neurologic disease. PMID:7944008

  19. CAR and PXR agonists stimulate hepatic bile acid and bilirubin detoxification and elimination pathways in mice.

    PubMed

    Wagner, Martin; Halilbasic, Emina; Marschall, Hanns-Ulrich; Zollner, Gernot; Fickert, Peter; Langner, Cord; Zatloukal, Kurt; Denk, Helmut; Trauner, Michael

    2005-08-01

    Induction of hepatic phase I/II detoxification enzymes and alternative excretory pumps may limit hepatocellular accumulation of toxic biliary compounds in cholestasis. Because the nuclear xenobiotic receptors constitutive androstane receptor (CAR) and pregnane X receptor (PXR) regulate involved enzymes and transporters, we aimed to induce adaptive alternative pathways with different CAR and PXR agonists in vivo. Mice were treated with the CAR agonists phenobarbital and 1,4-bis-[2-(3,5-dichlorpyridyloxy)]benzene, as well as the PXR agonists atorvastatin and pregnenolone-16alpha-carbonitrile. Hepatic bile acid and bilirubin-metabolizing/detoxifying enzymes (Cyp2b10, Cyp3a11, Ugt1a1, Sult2a1), their regulatory nuclear receptors (CAR, PXR, farnesoid X receptor), and bile acid/organic anion and lipid transporters (Ntcp, Oatp1,2,4, Bsep, Mrp2-4, Mdr2, Abcg5/8, Asbt) in the liver and kidney were analyzed via reverse-transcriptase polymerase chain reaction and Western blotting. Potential functional relevance was tested in common bile duct ligation (CBDL). CAR agonists induced Mrp2-4 and Oatp2; PXR agonists induced only Mrp3 and Oatp2. Both PXR and CAR agonists profoundly stimulated bile acid-hydroxylating/detoxifying enzymes Cyp3a11 and Cyp2b10. In addition, CAR agonists upregulated bile acid-sulfating Sult2a1 and bilirubin-glucuronidating Ugt1a1. These changes were accompanied by reduced serum levels of bilirubin and bile acids in healthy and CBDL mice and by increased levels of polyhydroxylated bile acids in serum and urine of cholestatic mice. Atorvastatin significantly increased Oatp2, Mdr2, and Asbt, while other transporters and enzymes were moderately affected. In conclusion, administration of specific CAR or PXR ligands results in coordinated stimulation of major hepatic bile acid/bilirubin metabolizing and detoxifying enzymes and hepatic key alternative efflux systems, effects that are predicted to counteract cholestasis. PMID:15986414

  20. Direct Antioxidant Properties of Bilirubin and Biliverdin. Is there a Role for Biliverdin Reductase?

    PubMed Central

    Jansen, Thomas; Daiber, Andreas

    2012-01-01

    Reactive oxygen species (ROS) and signaling events are involved in the pathogenesis of endothelial dysfunction and represent a major contribution to vascular regulation. Molecular signaling is highly dependent on ROS. But depending on the amount of ROS production it might have toxic or protective effects. Despite a large number of negative outcomes in large clinical trials (e.g., HOPE, HOPE-TOO), antioxidant molecules and agents are important players to influence the critical balance between production and elimination of reactive oxygen and nitrogen species. However, chronic systemic antioxidant therapy lacks clinical efficacy, probably by interfering with important physiological redox signaling pathways. Therefore, it may be a much more promising attempt to induce intrinsic antioxidant pathways in order to increase the antioxidants not systemically but at the place of oxidative stress and complications. Among others, heme oxygenase (HO) has been shown to be important for attenuating the overall production of ROS in a broad range of disease states through its ability to degrade heme and to produce carbon monoxide and biliverdin/bilirubin. With the present review we would like to highlight the important antioxidant role of the HO system and especially discuss the contribution of the biliverdin, bilirubin, and biliverdin reductase (BVR) to these beneficial effects. The BVR was reported to confer an antioxidant redox amplification cycle by which low, physiological bilirubin concentrations confer potent antioxidant protection via recycling of biliverdin from oxidized bilirubin by the BVR, linking this sink for oxidants to the NADPH pool. To date the existence and role of this antioxidant redox cycle is still under debate and we present and discuss the pros and cons as well as our own findings on this topic. PMID:22438843

  1. Association between Serum Bilirubin and Estimated Glomerular Filtration Rate among Diabetic Patients

    PubMed Central

    Katoh, Takeaki; Kawamoto, Ryuichi; Kohara, Katsuhiko; Miki, Tetsuro

    2015-01-01

    The subjects comprised 230 men aged 77 ± 10 (range: 50–100) years and 279 women aged 81 ± 10 (50–101) years that visited the medical department. We examined the relationship between increased serum bilirubin and renal function evaluated by estimated glomerular filtration rate (eGFR) using CKD-EPI equations modified by a Japanese coefficient. Compared with the fourth quartile in serum bilirubin (1.01–1.97 mg/dL), the nonadjusted, age and gender-adjusted, and multivariate-adjusted odds ratios {95% confidence interval (CI)} of eGFR <60 mL/min/1.73 m2 for the first quartile in serum bilirubin (0.13–0.50 mg/dL) were 2.08 (1.25–3.44), 1.82 (1.07–3.09), and 1.53 (0.83–2.81), respectively. Moreover, compared with the fourth quartile, nonadjusted, age and gender-adjusted, and multivariate-adjusted odds ratios (95% CI) of eGFR <45 mL/min/1.73 m2 for the first quartile were 3.50 (1.95–6.23), 3.12 (1.72–5.65), and 3.53 (1.71–7.26), respectively. The data were further stratified by gender, age, medication (antihypertensive, antidyslipidemic, and antidiabetic agents), and prevalence of cardiovascular disease (CVD). The standardized coefficients for eGFR were significant in all the subgroups other than the prevalence of CVD, and there were significant interactions between the two groups regarding CVD. Our data demonstrated an independent positive association between serum bilirubin and eGFR among diabetic patients.

  2. Growth Status and Its Relationship with Serum Lipids and Albumin in Children with Cystic Fibrosis.

    PubMed

    Fallahi, Gholam Hossein; Latifi, Sahar; Mahmoudi, Maryam; Kushki, Davood; Haghhi Ashtiani, Mohammad Taghi; Morteza, Afsaneh; Rezaei, Nima

    2016-04-01

    Cystic fibrosis (CF) is an autosomal recessive disease, which affects many organs as it impairs chloride channel. This study was performed to evaluate growth status and its relationship with some laboratory indices such as Cholesterol (chol), Triglyceride (TG), albumin and total protein in children with CF referred to pediatrics center. This study was designed as a cross-sectional study in one year section. Demographic features were compared with standard percentiles curves. Chol, TG, albumin, total protein, prothrombin time, and hemoglobin were measured. Stool exams were also performed. A questionnaire was designed to obtain a history of the first presentation of disease, birth weight, type of labor and parent relativity. In 52% of patients, failure to thrive (FTT) was the first presentation. Steatorrhea and respiratory infections were the first presentations, which were seen in 13.7% and 33% of the cases, respectively. The weight of 88% of patients was below the 15th percentile while 82% had a height percentile below 15th. Head circumference in 53% of patients was below the 15th percentile. There was a significant association between weight percentile and serum albumin and total protein (P=0.03 and P=0.007, respectively). There was also a significant relationship between height percentile and serum albumin and total protein (P<0.001 and P<0.000, respectively). The relationships between head circumference and serum albumin and total protein were also significant (P=0.006 and P<0.000, respectively). There was also a significant association between height percentile and hemoglobin. The decrease in anthropometric percentiles leads to decreased serum albumin and total protein. PMID:27309270

  3. Somatostatin inhibits the effect of secretin on bile flow and on hepatic bilirubin transport in the rat.

    PubMed Central

    Ricci, G L; Fevery, J

    1989-01-01

    Increasing amounts of porcine secretion (0.05 to 2.00 clinical units/h/100 g body wt) given to rats during a continuous infusion of bilirubin, increased bile flow and the apparent maximal biliary excretion of bilirubin ('Tm'). This increment was caused by an enhanced biliary output of bilirubin monoconjugates. The effect was dose dependent but maximal at a secretin infusion of 0.80 CU. Somatostatin 0.2 and 0.8 microgram/h/100 g body wt caused a dose related inhibition of the hepatic effects of secretin both on bile flow and on biliary output of bilirubin conjugates. As secretin elicits the release of somatostatin, a feed-back system could be envisaged whereby the somatostatin released stops the effects of secretin. PMID:2572517

  4. Bilirubin induces auditory neuropathy in neonatal guinea pigs via auditory nerve fiber damage.

    PubMed

    Ye, Hai-Bo; Shi, Hai-Bo; Wang, Jian; Ding, Da-Lian; Yu, Dong-Zhen; Chen, Zheng-Nong; Li, Chun-Yan; Zhang, Wei-Tian; Yin, Shan-Kai

    2012-11-01

    Bilirubin can cause temporary or permanent sensorineural deafness in newborn babies with hyperbilirubinemia. However, the underlying targets and physiological effects of bilirubin-induced damage in the peripheral auditory system are unclear. Using cochlear functional assays and electron microscopy imaging of the inner ear in neonatal guinea pigs, we show here that bilirubin exposure resulted in threshold elevation in both compound action potential (CAP) and auditory brainstem response (ABR), which was apparent at 1 hr and peaked 8 hr after drug administration. The threshold elevation was associated with delayed wave latencies and elongated interwave intervals in ABR and CAP. At 72 hr postinjection, these measures returned to control levels, except for the CAP amplitude. Cochlear microphonics remained unchanged during the experiment. Morphological abnormalities were consistent with the electrophysiological dysfunction, revealing fewer auditory nerve fibers (ANFs) in the basal turn, myelin sheath lesions of spiral ganglion neurons (SGNs) and ANFs, and loss of type 1 afferent endings beneath inner hair cells (IHCs) without loss of hair cells at 8 hr posttreatment. Similar to the electrophysiological findings, morphological changes were mostly reversed 10 days after treatment, except for the ANF reduction in the basal turn. These results suggest that hyperbilirubinemia in neonatal guinea pigs impaired auditory peripheral neuromechanisms that targeted mainly the IHC synapses and the myelin sheath of SGNs and their fibers. Our observations indicate a potential connection between hyperbilirubinemia and auditory neuropathy. PMID:22847875

  5. Interference of Bilirubin in the Determination of Magnesium with Methyl Thymol Blue

    PubMed Central

    Maksinovic, Rada; Ketin, Sonja; Biocanin, Rade

    2015-01-01

    Introduction: Jaundice is a disease named for the yellow color of the skin. This color is the result of elevated levels of bilirubin in the blood serum. In Roma from Krusevac region in the last few years have seen the emergence of jaundice. Material and methods: In 80 of them (40 suffering and 40 from control group) were performed tests of numerous parameters in the laboratories of the Health Center in Krusevac. Magnesium was determined by spectrophotometry with methyl thymol blue, titanium yellow and blue xylidene. Bilirubin was determined by Jandrešek Grofov’s method. Results: The results were within the expectations, in addition to magnesium which was determined with methyl thymol blue. In all patients suffering from jaundice concentration of magnesium (0.67 ±0.14 mmol/l) statistically was significantly lower than tested of the control group (0.91± 0.059 mmol/). There is no theoretical data to reduce the concentration of magnesium in serum as a result of jaundice. That’s why we determined magnesium both in the control group and in sufferings with two methods as the titanium yellow, and xylidene blew. With these two methods we obtained results that were examined were within normal limits. Conclusion: This has led us to conclude that the determination of bilirubin interferes with magnesium methyl thymol blue. PMID:26244045

  6. The urinary concentrating defect in the Gunn strain of rat. Role of bilirubin.

    PubMed

    Call, N B; Tisher, C C

    1975-02-01

    The role of high serum and tissue levels of unconjegated bilirubin in the pathogenesis of the impaired urinary concentrating ability was investigated in homozygous (jj) Gunn rats with the congenital absence of hepatic glucuronyl transferase. Continuous phototherapy with blue fluorescent lights at a wave length of 460 nm or oral cholestyramine feeding or both reduced serum levels of unconjugated hilirubin to levels consistently below 3.0 mg/100 ml for several weeks in both weanling and adult jj Gunn rats. The renal concentrating defect was already present in weanling jj Gunn rats by 21 days of age. In treated weanling jj animals, maximum concentrating ability and the concentration of urea and nonurea solutes in the papilla and medulla, determined after 24 h of fluid deprivation, were normal when compared to unaffected heterozygous (Jj) littermates. Solute-free water reabsorption which is reduced in jaundiced jj Gunn rats was restored to normal in treated weanling jj rats. The tissue concentration of unconjugated bilirubin was reduced throughout the papilla and inner and outer medulla in the treated jj rats in comparison with untreated jj littermates. The defect in urinary concentrating ability was only partially reversible and sometimes irreversible in adult jj rats, probably because of permanent renal parenchymal damage occurring secondary to massive crystalline deposits in the papilla and medulla. It is concluded that unconjugated bilirubin is directly involved in the pathogenesis of the concentrating defect in jaundiced jj Gunn rats. PMID:1127102

  7. Albumin in Burn Shock Resuscitation: A Meta-Analysis of Controlled Clinical Studies

    PubMed Central

    Greenhalgh, David G.; Wilkes, Mahlon M.

    2016-01-01

    Critical appraisal of outcomes after burn shock resuscitation with albumin has previously been restricted to small relatively old randomized trials, some with high risk of bias. Extensive recent data from nonrandomized studies assessing the use of albumin can potentially reduce bias and add precision. The objective of this meta-analysis was to determine the effect of burn shock resuscitation with albumin on mortality and morbidity in adult patients. Randomized and nonrandomized controlled clinical studies evaluating mortality and morbidity in adult patients receiving albumin for burn shock resuscitation were identified by multiple methods, including computer database searches and examination of journal contents and reference lists. Extracted data were quantitatively combined by random-effects meta-analysis. Four randomized and four nonrandomized studies with 688 total adult patients were included. Treatment effects did not differ significantly between the included randomized and nonrandomized studies. Albumin infusion during the first 24 hours showed no significant overall effect on mortality. However, significant statistical heterogeneity was present, which could be abolished by excluding two studies at high risk of bias. After those exclusions, albumin infusion was associated with reduced mortality. The pooled odds ratio was 0.34 with a 95% confidence interval of 0.19 to 0.58 (P < .001). Albumin administration was also accompanied by decreased occurrence of compartment syndrome (pooled odds ratio, 0.19; 95% confidence interval, 0.07–0.50; P < .001). This meta-analysis suggests that albumin can improve outcomes of burn shock resuscitation. However, the scope and quality of current evidence are limited, and additional trials are needed. PMID:25426807

  8. Significance and prognostic value of increased serum direct bilirubin level for lymph node metastasis in Chinese rectal cancer patients

    PubMed Central

    Gao, Chun; Fang, Long; Li, Jing-Tao; Zhao, Hong-Chuan

    2016-01-01

    AIM: To determine the significance of increased serum direct bilirubin level for lymph node metastasis (LNM) in Chinese rectal cancer patients, after those with known hepatobiliary and pancreatic diseases were excluded. METHODS: A cohort of 469 patients, who were treated at the China-Japan Friendship Hospital, Ministry of Health (Beijing, China), in the period from January 2003 to June 2011, and with a pathological diagnosis of rectal adenocarcinoma, were recruited. They included 231 patients with LNM (49.3%) and 238 patients without LNM. Follow-up for these patients was taken through to December 31, 2012. RESULTS: The baseline serum direct bilirubin concentration was (median/inter-quartile range) 2.30/1.60-3.42 μmol/L. Univariate analysis showed that compared with patients without LNM, the patients with LNM had an increased level of direct bilirubin (2.50/1.70-3.42 vs 2.10/1.40-3.42, P = 0.025). Multivariate analysis showed that direct bilirubin was independently associated with LNM (OR = 1.602; 95%CI: 1.098-2.338, P = 0.015). Moreover, we found that: (1) serum direct bilirubin differs between male and female patients; a higher concentration was associated with poor tumor classification; (2) as the baseline serum direct bilirubin concentration increased, the percentage of patients with LNM increased; and (3) serum direct bilirubin was associated with the prognosis of rectal cancer patients and higher values indicated poor prognosis. CONCLUSION: Higher serum direct bilirubin concentration was associated with the increased risk of LNM and poor prognosis in our rectal cancers. PMID:26937145

  9. Studies of the conformation of bilirubin and its dimethyl ester in dimethyl sulphoxide solutions by nuclear magnetic resonance.

    PubMed Central

    Kaplan, D; Navon, G

    1982-01-01

    The conformation of bilirubin and its dimethyl ester in dimethyl sulphoxide (DMSO) was investigated by n.m.r. spectroscopy. The chemical shifts of the pyrrole NH and Lactam protons of bilirubin and its dimethyl ester in DMSO indicate a strong interaction with the solvent. Inter-proton distances were calculated from nuclear Overhauser effects (NOE), selective and non-selective relaxation times (T1) and rotational correlation times taken from 13C relaxation times. The interproton distances indicate that the conformation of the skeleton of bilirubin and its dimethyl ester in DMSO is similar to that of bilirubin and mesobilirubin in the crystalline state and in chloroform solutions, except for a possible slight twist of the pyrrolenone rings about the methine bonds, which may be a consequence of solvation of the NH groups by DMSO. Unlike in chloroform solutions, no direct hydrogen-bonding occurs between the carboxylic acid and the lactam groups of bilirubin in DMSO, as shown by the absence of an NOE between these groups. The fast exchange of the pyrrole NH protons with 2H shows that no hydrogen-bonding occurs between these protons and the propionic residues, in line with their solvation by DMSO. From the above results, and from the slowness of the internal motion of the propionic residues of bilirubin and its dimethyl ester, it is concluded that these residues are tied to the skeleton via bound solvent molecules. PMID:6284124

  10. Unilobar Versus Bilobar Biliary Drainage: Effect on Quality of Life and Bilirubin Level Reduction

    PubMed Central

    Gamanagatti, Shivanand; Singh, Tejbir; Sharma, Raju; Srivastava, Deep N; Dash, Nihar Ranjan; Garg, Pramod Kumar

    2016-01-01

    Background: Percutaneous biliary drainage is an accepted palliative treatment for malignant biliary obstruction. Purpose: To assess the effect on quality of life (QOL) and bilirubin level reduction in patients with inoperable malignant biliary obstruction treated by unilobar or bilobar percutaneous transhepatic biliary drainage (PTBD). Materials and Methods: Over a period of 2 years, 49 patients (age range, 22–75 years) of inoperable malignant biliary obstruction were treated by PTBD. Technical and clinical success rates, QOL, patency rates, survival rates, and complications were recorded. Clinical success rates, QOL, and bilirubin reduction were compared in patients treated with complete (n = 21) versus partial (n = 28) liver parenchyma drainage. QOL before and 1 month after biliary drainage were analyzed retrospectively between these two groups. Results: Biliary drainage was successful in all 49 patients, with an overall significant reduction of the postintervention bilirubin levels (P < 0.001) resulting in overall clinical success rate of 89.97%. Clinical success rates were similar in patients treated with whole-liver drainage versus partial-liver drainage. Mean serum bilirubin level before PTBD was 19.85 mg/dl and after the procedure at 1 month was 6.02 mg/dl. The mean baseline functional score was 39.35, symptom scale score was 59.55, and global health score was 27.45. At 1 month, mean functional score was 61.25, symptom scale score was 36.0 4, and global health score was 56.33, with overall significant improvement in QOL (<0.001). There was a statistically significant difference in the improvement of the QOL scores (P = 0.002), among patients who achieved clinical success, compared with those patients who did not achieve clinical success at 1 month. We did not find any significant difference in the QOL scores in patients according to the amount of liver drained (unilateral or bilateral drainage), the type of internalization used (ring biliary or stent

  11. Exploring the interaction between picoplatin and human serum albumin: The effects on protein structure and activity.

    PubMed

    Wang, Yanqing; Wu, Peirong; Zhou, Xinchun; Zhang, Hongmei; Qiu, Ligan; Cao, Jian

    2016-09-01

    For the first time, the effects of picoplatin on the structure and esterase-like catalytic activity of human serum albumin (HSA) have been investigated by spectroscopic approaches and molecular modeling. The circular dichroism (CD) spectral examinations indicated that the binding of picoplatin with HSA induced a slight decrease of a-helix content of protein and unfolded the constituent polypeptides of the protein. The synchronous fluorescence and three-dimensional fluorescence spectral methods were used to estimate the effect of picoplatin on the micro-environmental changes of the Trp and Tyr residues of HSA, indicating that the micro-environment around the Tyr and Trp residue is partly disturbed by picoplatin. UV-vis absorption spectral result indicated the formation of the ground state complex between picoplatin with HSA. The ANS binding assay indicated the existence of competitive combination of picoplatin and ANS with HSA. The studies on the effects of picoplatin on the binding of HSA with bilirubin and heme showed that picoplatin binding caused a change of angle between two chromophores of bound bilirubin and the binding site of picoplatin does not locate in subdomain IB in HSA that bound with heme. The molecular modeling results showed that picoplatin binds to the connection between domain I and domain II by hydrophobic, hydrogen bonds, and van der Waals forces. In addition, HSA maintains most of its esterase activity in the presence of picoplatin. The investigations on how picoplatin interacts with HSA are important for the understanding of the anticancer mechanism and toxicity of platinum-based anticancer drug. PMID:27484966

  12. 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

  13. 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

    2016-01-01

    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

  14. 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.

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

    PubMed

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

    1994-12-15

    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. PMID:7813459

  16. 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.

  17. Utility of bilirubins and bile acids as endogenous biomarkers for the inhibition of hepatic transporters.

    PubMed

    Watanabe, Tomoko; Miyake, Manami; Shimizu, Toshinobu; Kamezawa, Miho; Masutomi, Naoya; Shimura, Takesada; Ohashi, Rikiya

    2015-04-01

    It is useful to identify endogenous substrates for the evaluation of drug-drug interactions via transporters. In this study, we investigated the utility of bilirubins, substrates of OATPs and MRP2, and bile acids and substrates of NTCP and BSEP, as biomarkers for the inhibition of transporters. In rats administered 20 and 80 mg/kg rifampicin, the plasma levels of bilirubin glucuronides were elevated, gradually decreased, and almost returned to the baseline level at 24 hours after administration without an elevation of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). This result indicates the transient inhibition of rOatps and/or rMrp2. Although the correlation between free plasma concentrations and IC50 values of rOatps depended on the substrates used in the in vitro studies, the inhibition of rOatps by rifampicin was confirmed in the in vivo study using valsartan as a substrate of rOatps. In rats administered 10 and 30 mg/kg cyclosporin A, the plasma levels of bile acids were elevated and persisted for up to 24 hours after administration without an elevation of ALT and AST. This result indicates the continuous inhibition of rNtcp and/or rBsep, although there were differences between the free plasma or liver concentrations and IC50 values of rNtcp or rBsep, respectively. This study suggests that the monitoring of bilirubins and bile acids in plasma is useful in evaluating the inhibitory potential of their corresponding transporters. PMID:25581390

  18. Mitochondrial targeting of bilirubin regulatory enzymes: An adaptive response to oxidative stress

    SciTech Connect

    Muhsain, Siti Nur Fadzilah; Lang, Matti A.; Abu-Bakar, A'edah

    2015-01-01

    The intracellular level of bilirubin (BR), an endogenous antioxidant that is cytotoxic at high concentrations, is tightly controlled within the optimal therapeutic range. We have recently described a concerted intracellular BR regulation by two microsomal enzymes: heme oxygenase 1 (HMOX1), essential for BR production and cytochrome P450 2A5 (CYP2A5), a BR oxidase. Herein, we describe targeting of these enzymes to hepatic mitochondria during oxidative stress. The kinetics of microsomal and mitochondrial BR oxidation were compared. Treatment of DBA/2J mice with 200 mg pyrazole/kg/day for 3 days increased hepatic intracellular protein carbonyl content and induced nucleo-translocation of Nrf2. HMOX1 and CYP2A5 proteins and activities were elevated in microsomes and mitoplasts but not the UGT1A1, a catalyst of BR glucuronidation. A CYP2A5 antibody inhibited 75% of microsomal BR oxidation. The inhibition was absent in control mitoplasts but elevated to 50% after treatment. An adrenodoxin reductase antibody did not inhibit microsomal BR oxidation but inhibited 50% of mitochondrial BR oxidation. Ascorbic acid inhibited 5% and 22% of the reaction in control and treated microsomes, respectively. In control mitoplasts the inhibition was 100%, which was reduced to 50% after treatment. Bilirubin affinity to mitochondrial and microsomal CYP2A5 enzyme is equally high. Lastly, the treatment neither released cytochrome c into cytoplasm nor dissipated membrane potential, indicating the absence of mitochondrial membrane damage. Collectively, the observations suggest that BR regulatory enzymes are recruited to mitochondria during oxidative stress and BR oxidation by mitochondrial CYP2A5 is supported by mitochondrial mono-oxygenase system. The induced recruitment potentially confers membrane protection. - Highlights: • Pyrazole induces oxidative stress in the mouse liver. • Pyrazole-induced oxidative stress induces mitochondrial targeting of key bilirubin regulatory enzymes, HMOX1

  19. Comparison of antioxidant properties of different therapeutic albumin preparations.

    PubMed

    Plantier, Jean-Luc; Duretz, Véronique; Devos, Véronique; Urbain, Rémi; Jorieux, Sylvie

    2016-07-01

    Albumin displays several important functions for homeostasis amongst which the maintenance of the plasma redox-state. The study aim was to compare the redox state of pharmaceutical human albumin preparations since it reflects the oxidation-reduction status of the surrounding environment. Using an array of analytical methods, four commercially available albumins were compared with respect to their structural characteristics (cobalt ion binding, glycation, spectrophotometric and fluorometric profiles) and their ability to scavenge hydroxyl, peroxyl or free radicals. The different albumins exhibited a similar structural profile as well as hydroxyl and peroxyl scavenging activities. By contrast, the albumin from LFB (Vialebex(®)) possessed a significantly higher capacity to transfer electrons to DPPH, as compared with other albumins that was correlated with the level of free cysteine-34. Commercially available albumins differed for some of their antioxidant properties. The albumin preparation possessing the highest level of free cysteine-34 exhibited the highest antioxidant potential. PMID:27156143

  20. Effect of different albumin concentrations in extracorporeal circuit prime on perioperative fluid status in young children.

    PubMed

    Yu, Kun; Liu, Yinglong; Hei, Feilong; Li, Jingwen; Long, Cun

    2008-01-01

    This study examined the effects of different dosages of albumin priming for extracorporeal circuit (ECC) on perioperative fluid status and fluid management in young children. A total of 151 consecutive pediatric patients (2-36 months old) scheduled for open heart surgery, were divided into two groups randomly, to receive either a 3% albumin solution (L group, n = 68) or a 5% albumin (H group, n = 83). Perioperative fluid intake, urine output, blood loss, diuretic dosage, the use of allogeneic blood products, ultrafiltration, and daily balance were recorded for 24 hrs in intensive care unit (ICU). Serial hematocrits, colloid osmotic pressure (COP) were measured. Outcomes and complications were documented. There were no significant differences in demographics, types of surgical procedures, baseline data such as hemoglobin, COP, and serum albumin. Patients in H group had significantly higher COPs, less urine output and more diuretic usage during operation and postoperatively (p < 0.05); at 6 hrs postoperatively, there were no differences between two groups. No statistically significant differences were found between the two groups in blood loss and the amount of allogenic blood products infused, length of mechanical ventilation, ICU or hospital stay, complications, or mortality. Higher concentration of albumin prime in ECC showed decreased positive fluid balances, but produced less urine output and required more diuretic usage postoperatively. Thus, no significant clinical benefit resulted from the increased dosage. PMID:18812733

  1. Trajectories of Serum Albumin Predict Survival of Peritoneal Dialysis Patients

    PubMed Central

    Chiu, Ping-Fang; Tsai, Chun-Chieh; Wu, Chia-Lin; Yang, Tse-Yen; Liou, Hung-Hsiang; Chen, Hung-Lin; Kor, Chew-Teng; Chang, Chia-Chu; Chang, Horng-Rong

    2016-01-01

    Abstract Although initial serum albumin level is highly associated with overall and cardiovascular mortality in peritoneal dialysis (PD) patients, we consider that the dynamic change and trend of albumin after initiation of PD are also essential. We enrolled patients who received PD for more than 3 months from January 1999 to March 2014. We categorized these patients into 2 groups by the difference in serum albumin level (Δalbumin = difference between peak with initial albumin level = peak albumin level − initial albumin level) after PD. The patients with Δalbumin < 0.2 g/dL (median level) were considered as group A (n, number = 238) and those with Δalbumin ≥ 0.2 g/dL were considered as group B (n = 278). Further, we stratified these patients into quartiles: Q1 Δalbumin < −0.2 g/dL; Q2, −0.2 ≦∼ <0.2 g/dL; Q3, 0.2 ≦∼ <0.6 g/dL; and Q4, ≥0.6 g/dL. Regression analysis was performed to determine the correlation of initial albumin and Δalbumin. Group A patients presented with higher levels of serum albumin (3.71 ± 0.54 vs 3.04 ± 0.55 g/dL; P < 0.001) and hematocrit as well as better initial residual renal function. However, those in group A had lower serum albumin increment and downward-sloped trends after dialysis. In contrast, the albumin trend was upward sloped and the increment of albumin was remarkable in group B, despite the high prevalence of cardiovascular diseases and diabetes. Overtime, group A patients had poorer survival and experienced more frequent and longer hospitalizations. Group Q1 patients with least albumin increment had worst survival. Group Q4 patients with lowest initial albumin also had poor survival. Age, diabetes, cardiovascular diseases, BMI, initial albumin, and Δalbumin could affect patient outcomes independently. Regression analysis showed a better outcome can be obtained if the initial albumin level is at least above 3.15 g/dL. (Initial albumin level

  2. 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

  3. 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.

  4. Impact of Rhesus disease on the global problem of bilirubin-induced neurologic dysfunction.

    PubMed

    Zipursky, Alvin; Bhutani, Vinod K

    2015-02-01

    Clinical experience with Rhesus (Rh) disease and its post-icteric sequelae is limited among high-income countries because of nearly over four decades of effective prevention care. We hypothesized that Rh disease is prevalent in other regions of the world because it is likely that protection is limited or non-existent. Following a worldwide study, it has been concluded that Rh hemolytic disease is a significant public health problem resulting in stillbirths and neonatal deaths, and is a major cause of severe hyperbilirubinemia with its sequelae, kernicterus and bilirubin-induced neurologic dysfunction. Knowing that effective Rh-disease prophylaxis depends on maternal blood-type screening, healthcare afforded to the high-risk mothers needs to be free of bottlenecks and coupled with unfettered access to effective Rh-immunoglobulin. Future studies that match the universal identification of Rh-negative status of women and targeted use of immunoprophylaxis to prevent childhood bilirubin neurotoxicity are within reach, based on vast prior experiences. PMID:25582277

  5. Method for Estimating Bilirubin Isomerization Efficiency in Phototherapy to Treat Neonatal Jaundice

    NASA Astrophysics Data System (ADS)

    Lisenko, S. A.; Kugeiko, M. M.

    2014-11-01

    We propose a method for quantitative assessment of the efficacy of phototherapy to treat neonatal jaundice using the diffuse reflectance spectrum for the newborn's skin, based on the analytical dependence of the measured spectrum on the structural and morphological parameters of the skin, affecting the optical conditions in the medium, and an algorithm for rapid calculation of the bilirubin photoisomerization rate in the skin tissues as a function of the structural and morphological parameters of the skin and the wavelength of the exciting radiation. From the results of a numerical simulation of the process of radiation transport in the skin, we assess the stability of our method to variations in the scattering properties of the skin and the concentrations of its optically active chromophores (melanin, oxyhemoglobin, deoxyhemoglobin). We show that in order to achieve the maximum efficacy of phototherapy, we should use light from the range 484-496 nm. In this case, the intensity of the exciting radiation should be selected individually for each newborn according to the bilirubin photoisomerization rate characteristic for it.

  6. Unconjugated Bilirubin exerts Pro-Apoptotic Effect on Platelets via p38-MAPK activation

    PubMed Central

    NaveenKumar, Somanathapura K.; Thushara, Ram M.; Sundaram, Mahalingam S.; Hemshekhar, Mahadevappa; Paul, Manoj; Thirunavukkarasu, Chinnasamy; Basappa; Nagaraju, Ganesh; Raghavan, Sathees C.; Girish, Kesturu S.; Kemparaju, Kempaiah; Rangappa, Kanchugarakoppal S.

    2015-01-01

    Thrombocytopenia is one of the most frequently observed secondary complications in many pathological conditions including liver diseases, where hyperbilirubinemia is very common. The present study sought to find the cause of thrombocytopenia in unconjugated hyperbilirubinemic conditions. Unconjugated bilirubin (UCB), an end-product of heme catabolism, is known to have pro-oxidative and cytotoxic effects at high serum concentration. We investigated the molecular mechanism underlying the pro-apoptotic effect of UCB on human platelets in vitro, and followed it up with studies in phenylhydrazine-induced hyperbilirubinemic rat model and hyperbilirubinemic human subjects. UCB is indeed found to significantly induce platelet apoptotic events including elevated endogenous reactive oxygen species generation, mitochondrial membrane depolarization, increased intracellular calcium levels, cardiolipin peroxidation and phosphatidylserine externalization (p < 0.001) as evident by FACS analysis. The immunoblots show the elevated levels of cytosolic cytochrome c and caspase activation in UCB-treated platelets. Further, UCB is found to induce mitochondrial ROS generation leading to p38 activation, followed by downstream activation of p53, ultimately resulting in altered expression of Bcl-2 and Bax proteins as evident from immunoblotting. All these parameters conclude that elevated unconjugated bilirubin causes thrombocytopenia by stimulating platelet apoptosis via mitochondrial ROS-induced p38 and p53 activation. PMID:26459859

  7. Drug Delivery Vehicles Based on Albumin-Polymer Conjugates.

    PubMed

    Jiang, Yanyan; Stenzel, Martina

    2016-06-01

    Albumin has been a popular building block to create nanoparticles for drug delivery purposes. The performance of albumin as a drug carrier can be enhanced by combining protein with polymers, which allows the design of carriers to encompass a broader spectrum of drugs while features unique to synthetic polymers such as stimuli-responsiveness are introduced. Nanoparticles based on polymer-albumin hybrids can be divided into two classes: one that carries album as a bioactive surface coating and the other that uses albumin as biocompatible, although nonbioactive, building block. Nanoparticles with bioactive albumin surface coating can either be prepared by self-assembly of albumin-polymer conjugates or by postcoating of existing nanoparticles with albumin. Albumin has also been used as building block, either in its native or denatured form. Existing albumin nanoparticles are coated with polymers, which can influence the degradation of albumin or impact on the drug release. Finally, an alternative way of using albumin by denaturing the protein to generate a highly functional chain, which can be modified with polymer, has been presented. These albumin nanoparticles are designed to be extremely versatile so that they can deliver a wide variety of drugs, including traditional hydrophobic drugs, metal-based drugs and even therapeutic proteins and siRNA. PMID:26947019

  8. 21 CFR 866.5040 - Albumin immunological test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Albumin immunological test system. 866.5040... (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5040 Albumin immunological test system. (a) Identification. An albumin immunological test system is a device that consists...

  9. Fluorescence excitation spectrum of bilirubin in blood: a model for the action spectrum for phototherapy of neonatal jaundice.

    PubMed

    Lamola, Angelo A; Russo, Marie

    2014-01-01

    A recent report (Lamola et al. 2013 Pediatric Research, 74, 54-60) presents a semiempirical model for facile calculation of an action spectrum for bilirubin photochemistry in vivo using the most current knowledge of the optics of neonatal skin. The calculations indicate that competition for phototherapy light by hemoglobin in the skin is the predominant factor that defines the spectrum of light absorbed by bilirubin. If the latter is correct, a valid physical analog of the calculated spectrum is the excitation spectrum of bilirubin in blood. The fluorescence excitation spectrum was recorded and, indeed, found to be very similar to the calculated spectrum. Both spectra exhibit maxima near 476 nm and widths at half height of about 50 nm. This result supports the conclusion that light between 460 and 490 nm is most effective for phototherapy of neonatal jaundice. PMID:23998276

  10. Molecular basis of bilirubin UDP-glucuronosyltransferase induction in spontaneously diabetic rats, acetone-treated rats and starved rats.

    PubMed Central

    Braun, L; Coffey, M J; Puskás, F; Kardon, T; Nagy, G; Conley, A A; Burchell, B; Mandl, J

    1998-01-01

    The co-ordinated induction of several hepatic drug-metabolizing enzymes is a common feature in the regulation of drug biotransformation under normal and pathological conditions. In the present study the activity and expression of bilirubin UDP-glucuronosyltransferase (UGT1A1) were investigated in livers of BioBreeding/Worcester diabetic, fasted and acetone-treated rats. Bilirubin glucuronidation was stimulated by all three treatments; this was correlated with an increase in the UGT1A1 protein concentration in hepatic microsomes. Transcriptional induction of UGT1A1 was also observed in diabetes and starvation but not with acetone treatment, which apparently caused translational stabilization of the enzyme protein. The hormonal/metabolic alterations in diabetes and starvation might be a model for postnatal development. The sudden interruption of maternal glucose supply signals the enhanced expression of UGT1A1, giving a novel explanation for the physiological induction of bilirubin glucuronidation in newborn infants. PMID:9841869

  11. Comparison Between Measured and Calculated Free Calcium Values at Different Serum Albumin Concentrations

    PubMed Central

    Mir, Altaf Ahmad; Goyal, Bela; Datta, Sudip Kumar; Ikkurthi, Saidaiah; Pal, Arnab

    2016-01-01

    Introduction: Free ionic calcium is the metabolically active component of total calcium (TCa) in blood. However, most laboratories report TCa levels that are dependent on serum albumin concentration. Hence, several formulae have evolved to calculate free calcium levels from TCa after adjustment for albumin. However, free calcium can directly be measured using direction selective electrodes rather than spectrophotometric methods used in autoanalyzers. Objectives: This study compares the levels of free calcium obtained by measurement by direct ion selective electrode (ISE) and the one calculated as a function of TCa by formulae. Materials and Methods: A total of 254 serum samples submitted to clinical biochemistry laboratory of a tertiary care hospital were analyzed for total protein, albumin, and TCa by standard spectrophotometric methods and for free calcium by direct ISE. Three commonly used formulae viz. Orrell, Berry et al. and Payne et al. were used to calculate adjusted TCa. Calculated free calcium was obtained by taking 50% of these values. Results: A significant difference (P < 0.05) was observed between calculated free calcium by all the three formulae and measured free calcium estimated by direct ISE using paired t-test and Bland–Altman plots. Conclusion: Formulae for predicting free calcium by estimating TCa and albumin lacks consistency in prediction and free calcium should be evaluated by direct measurement. PMID:27365914

  12. Zinc inhibits glycation induced structural, functional modifications in albumin and protects erythrocytes from glycated albumin toxicity.

    PubMed

    Tupe, Rashmi; Kulkarni, Amruta; Adeshara, Krishna; Sankhe, Neena; Shaikh, Shamim; Dalal, Sayli; Bhosale, Siddharth; Gaikwad, Sushama

    2015-08-01

    The present work aims to investigate the concentration and time dependant effect of zinc on the in vitro non enzymatic modifications of albumin by diabetic levels of glucose. Further, preventive and curative effect of zinc was studied by adding zinc before and after initiation of glycation respectively. Glycation of albumin was done at different concentrations of zinc (125, 250 and 500 μM) at different time intervals (21, 28 and 35 days) with appropriate controls. The antiglycation potential of zinc was assessed by estimating different markers of albumin glycation (fructosamines, carbonyls, bound sugar, AGEs), structural modifications (free amino, thiol group, β amyloid, native PAGE, ANS binding, fluorescence lifetime decay and CD analysis) and functional properties (antioxidant activity, hemolysis). Zinc at highest concentration (500 μM) significantly reduced modifications of albumin which was comparable to aminoguanidine and also protected secondary and tertiary structure of albumin after 28 days of incubation. Zinc exhibited significant protective effect on erythrocytes by inhibiting hemolysis. Thus the present study indicate preventive mode of albumin glycation inhibition by zinc. PMID:26027608

  13. The role of gamma-aminobutyric acid/glycinergic synaptic transmission in mediating bilirubin-induced hyperexcitation in developing auditory neurons.

    PubMed

    Yin, Xin-Lu; Liang, Min; Shi, Hai-Bo; Wang, Lu-Yang; Li, Chun-Yan; Yin, Shan-Kai

    2016-01-01

    Hyperbilirubinemia is a common clinical phenomenon observed in human newborns. A high level of bilirubin can result in severe jaundice and bilirubin encephalopathy. However, the cellular mechanisms underlying bilirubin excitotoxicity are unclear. Our previous studies showed the action of gamma-aminobutyric acid (GABA)/glycine switches from excitatory to inhibitory during development in the ventral cochlear nucleus (VCN), one of the most sensitive auditory nuclei to bilirubin toxicity. In the present study, we investigated the roles of GABAA/glycine receptors in the induction of bilirubin hyperexcitation in early developing neurons. Using the patch clamp technique, GABAA/glycine receptor-mediated spontaneous inhibitory synaptic currents (sIPSCs) were recorded from bushy and stellate cells in acute brainstem slices from young mice (postnatal day 2-6). Bilirubin significantly increased the frequency of sIPSCs, and this effect was prevented by pretreatments of slices with either fast or slow Ca(2+) chelators BAPTA-AM and EGTA-AM suggesting that bilirubin can increase the release of GABA/glycine via Ca(2+)-dependent mechanisms. Using cell-attached recording configuration, we found that antagonists of GABAA and glycine receptors strongly attenuated spontaneous spiking firings in P2-6 neurons but produced opposite effect in P15-19 neurons. Furthermore, these antagonists reversed bilirubin-evoked hyperexcitability in P2-6 neurons, indicating that excitatory action of GABA/glycinergic transmission specifically contribute to bilirubin-induced hyperexcitability in the early stage of development. Our results suggest that bilirubin-induced enhancement of presynaptic release GABA/Glycine via Ca(2+)-dependent mechanisms may play a critical role in mediating neuronal hyperexcitation associated with jaundice, implicating potential new strategies for predicting, preventing, and treating bilirubin neurotoxicity. PMID:26476400

  14. Efficacy of extracorporeal albumin dialysis for acute kidney injury due to cholestatic jaundice nephrotoxicity.

    PubMed

    Sens, Florence; Bacchetta, Justine; Rabeyrin, Maud; Juillard, Laurent

    2016-01-01

    We report a case of a 37-year-old man with Maturity Onset Diabetes of the Youth (MODY) type 5, admitted for an episode of cholestasis and a simultaneous acute kidney injury (AKI). Chronic liver disease was due to a mutation in the transcription factor 2 (TCF2) gene, thus highlighting the need for a close liver follow-up in these patients. AKI was attributed to a cholemic nephropathy based on the following rationale: (1) alternative diagnoses were actively ruled out; (2) the onset of AKI coincided with the onset of severe hyperbilirubinaemia; (3) renal pathology showed large bile tubular casts and a marked tubular necrosis and (4) creatinine serum dramatically decreased when bilirubin levels improved after the first sessions of extracorporeal albumin dialysis (ECAD), thus suggesting its role in renal recovery. Even though cholestasis can precipitate renal injury, the diagnosis of cholemic nephropathy could require a renal biopsy at times. Future studies should confirm the benefits of ECAD in cholemic nephropathy. PMID:27389722

  15. Bilirubin conjugates of human bile. The excretion of bilirubin as the acyl glycosides of aldobiouronic acid, pseudoaldobiouronic acid and hexuronosylhexuronic acid, with a branched-chain hexuronic acid as one of the components of hexuronosylhexuronide

    PubMed Central

    Kuenzle, Clive C.

    1970-01-01

    Structure elucidations have been performed on the bilirubin conjugates isolated from human hepatic bile as the phenylazo derivatives. The major bilirubin conjugates are excreted, not as was formerly thought in the form of glucuronides, but as the acyl glycosides of aldobiouronic acid, pseudoaldobiouronic acid and hexuronosylhexuronic acid. The isolated aldobiouronides are proposed to have the structures of an acyl 6-O-hexopyranosyluronic acid-hexopyranoside, an acyl 4-O-hexofuranosyluronic acid-d-glucopyranoside, and an acyl 4-O-β-d-glucofuranosyluronic acid-d-glucopyranoside respectively, with the acyl radicals being those of the phenylazo derivative of bilirubin. The pseudoaldobiouronide is suggested to be the acyl 4-O-α-d-glucofuranosyl-β-d -glucopyranosiduronic acid, with the acyl radical being that of the phenylazo derivative of vinylneoxanthobilirubinic acid. The hexuronosylhexuronide presumably is the acyl 4-O-(3-C-hydroxymethylribofuranosyluronic acid)-β-d-glucopyranosiduronic acid, with the acyl radical being that of the phenylazo derivative of bilirubin. The 3-C-hydroxymethylriburonic acid, isolated as one of the components of the hexuronosylhexuronide, is the first natural branched-chain hexuronic acid to be detected, and the first branched-chain sugar ever detected in humans. PMID:5500303

  16. Serum albumin and muscle measures in a cohort of healthy young and old participants.

    PubMed

    Reijnierse, E M; Trappenburg, M C; Leter, M J; Sipilä, S; Stenroth, L; Narici, M V; Hogrel, J Y; Butler-Browne, G; McPhee, J S; Pääsuke, M; Gapeyeva, H; Meskers, C G M; Maier, A B

    2015-10-01

    Consensus on clinically valid diagnostic criteria for sarcopenia requires a systematical assessment of the association of its candidate measures of muscle mass, muscle strength, and physical performance on one side and muscle-related clinical parameters on the other side. In this study, we systematically assessed associations between serum albumin as a muscle-related parameter and muscle measures in 172 healthy young (aged 18-30 years) and 271 old participants (aged 69-81 year) from the European MYOAGE study. Muscle measures included relative muscle mass, i.e., total- and appendicular lean mass (ALM) percentage, absolute muscle mass, i.e., ALM/height(2) and total lean mass in kilograms, handgrip strength, and walking speed. Muscle measures were standardized and analyzed in multivariate linear regression models, stratified by age. Adjustment models included age, body composition, C-reactive protein and lifestyle factors. In young participants, serum albumin was positively associated with lean mass percentage (p = 0.007) and with ALM percentage (p = 0.001). In old participants, serum albumin was not associated with any of the muscle measures. In conclusion, the association between serum albumin and muscle measures was only found in healthy young participants and the strongest for measures of relative muscle mass. PMID:26310888

  17. Albumin infusion in humans does not model exercise induced hypervolaemia after 24 hours

    NASA Technical Reports Server (NTRS)

    Haskell, A.; Gillen, C. M.; Mack, G. W.; Nadel, E. R.

    1998-01-01

    We rapidly infused 234 +/- 3 mL of 5% human serum albumin in eight men while measuring haematocrit, haemoglobin concentration, plasma volume (PV), albumin concentration, total protein concentration, osmolality, sodium concentration, renin activity, aldosterone concentration, and atrial natriuretic peptide concentration to test the hypotheses that plasma volume expansion and plasma albumin content expansion will not persist for 24 h. Plasma volume and albumin content were expanded for the first 6 h after infusion (44.3 +/- 1.9-47.2 +/- 2.0 mL kg-1 and 1.9 +/- 0.1-2.1 +/- 0.1 g kg-1 at pre-infusion and 1 h, respectively, P < 0.05), but by 24 h plasma volume and albumin content decreased significantly from 1 h post-infusion and were not different from pre-infusion (44.8 +/- 1.9 mL kg-1 and 1.9 +/- 0.1 g kg-1, respectively). Plasma aldosterone concentration showed a significant effect of time over the 24 h after infusion (P < 0.05), and showed a trend to decrease at 2 h after infusion (167.6 +/- 32.5(-1) 06.2 +/- 13.4 pg mL-1, P = 0.07). These data demonstrate that a 6.8% expansion of plasma volume and 10.5% expansion of plasma albumin content by infusion does not remain in the vascular space for 24 h and suggest a redistribution occurs between the intravascular space and interstitial fluid space.

  18. (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.

  19. (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.

  20. Ultrafast deactivation of bilirubin: dark intermediates and two-photon isomerization.

    PubMed

    Carreira-Blanco, Carlos; Singer, Patrick; Diller, Rolf; Luis Pérez Lustres, J

    2016-03-01

    Bilirubin is a neurotoxic product responsible for neonatal jaundice, which is generally treated by phototherapy. The photoreaction involves ultrafast internal conversion via an elusive intermediate and Z-E isomerization with minor yield (less than 3% in solution). The structure of the intermediate remains unclear. Here, the combination of UV-vis and mid-IR ultrafast transient absorption spectroscopy reports a comprehensive picture of the mechanism and provides essential structural information about the intermediate species. Thus, spectral dynamics during the earliest ps unveils a wavepacket travelling from the Franck-Condon region to the crossing point with a dark state. The latter shows a tighter molecular skeleton than the ground state and decays with 15 ps time constant. Remarkably, the relative contribution of a non-decaying component increases linearly with pump energy, suggesting that Z-E isomerization could also be triggered by two-photon excitation. Implications for the photochemistry of protein-bound open tetrapyrroles are discussed. PMID:26887629

  1. The role of albumin in nutritional support.

    PubMed

    Mobarhan, S

    1988-12-01

    Hypoalbuminemia is considered one of the hallmarks of protein-calorie malnutrition and chronic liver disease. Recently, serum albumin has also been proposed as a critical predictor of the response to nutritional support and tolerance to enteral feeding in critically ill patients. Albumin is essential for maintenance of plasma colloidal osmotic pressure, prevention of edema, and transport of certain drugs and nutrients. Experimental studies have shown that rapid plasma expansion and reduced plasma protein concentration and osmotic pressure induce a net secretion of sodium and water into the small intestinal lumen. However, the effects of chronic hypoalbuminemia per se on intestinal absorption, independent of malnutrition, have not been fully studied. It is documented that both chronic illness and malnutrition may profoundly affect intestinal anatomical structure and function, inducing some degree of malabsorption. In the last few years, some have advocated albumin infusion to improve clinical response to patients with hypoalbuminemia receiving parenteral nutritional support or to reduce intestinal intolerance and diarrhea in patients receiving enteral tube feeding. A review of the literature shows that both clinical and experimental data to support these suggestions are scarce and further investigations are needed. Hypoalbuminemia is one of many parameters of malnutrition, and it is unlikely that correction of a single parameter for a short time would lead to major clinical benefits. PMID:3147998

  2. Serum albumin complexation of acetylsalicylic acid metabolites.

    PubMed

    Jurkowski, Wiktor; Porebski, Grzegorz; Obtułowicz, Krystyna; Roterman, Irena

    2009-06-01

    One possible origin of the type I hypersensitivity reaction is reaction of drugs such as acetylsalicylic acid and its metabolites being complexed with human serum albumin. Albumin, being transporting molecule abundant in blood plasma is able to bind large array of ligands varying from small single carbon particles to long hydrophobic tailed lipidic acids (e.g. myristic acid). This non specificity is possible because of multi domain scaffold and large flexibility of inter-domain loops, which results in serious reorientation of domains. Hypothesis that acetylsalicylic acid metabolites may play indirect role in activation of allergic reaction has been tested. Binding of acetylsalicylic acid metabolites in intra-domain space causes significant increase of liability of domains IIIA and IIIB. One of metabolites, salicyluric acid, once is bound causes distortion and partial unfolding of helices in domains IA, IIB and IIIB. Changed are both directions and amplitude of relative motions as well as intra-domain distances. In result albumin is able to cross-link of adjacent IgE receptors which subsequently starts allergic reaction. PMID:19689242

  3. Heme oxygenase-1-derived bilirubin counteracts HIV protease inhibitor-mediated endothelial cell dysfunction.

    PubMed

    Liu, Xiao-Ming; Durante, Zane E; Peyton, Kelly J; Durante, William

    2016-05-01

    The use of HIV protease inhibitors (PIs) has extended the duration and quality of life for HIV-positive individuals. However there is increasing concern that this antiviral therapy may promote premature cardiovascular disease by impairing endothelial cell (EC) function. In the present study, we investigated the effect of HIV PIs on EC function and determined if the enzyme heme oxygenase (HO-1) influences the biological action of these drugs. We found that three distinct PIs, including ritonavir, atazanavir, and lopinavir, stimulated the expression of HO-1 protein and mRNA. The induction of HO-1 was associated with an increase in NF-E2-related factor-2 (Nrf2) activity and reactive oxygen species (ROS). PIs also stimulated HO-1 promoter activity and this was prevented by mutating the antioxidant responsive element or by overexpressing dominant-negative Nrf2. In addition, the PI-mediated induction of HO-1 was abolished by N-acetyl-l-cysteine and rotenone. Furthermore, PIs blocked EC proliferation and migration and stimulated the expression of intercellular adhesion molecule-1 and the adhesion of monocytes on ECs. Inhibition of HO-1 activity or expression potentiated the anti-proliferative and inflammatory actions of PIs which was reversed by bilirubin but not carbon monoxide. Alternatively, adenovirus-mediated overexpression of HO-1 attenuated the growth-inhibitory and inflammatory effect of PIs. In contrast, blocking HO-1 activity failed to modify the anti-migratory effect of the PIs. Thus, induction of HO-1 via the ROS-Nrf2 pathway in human ECs counteracts the anti-proliferative and inflammatory actions of PIs by generating bilirubin. Therapeutic approaches targeting HO-1 may provide a novel approach in preventing EC dysfunction and vascular disease in HIV-infected patients undergoing antiretroviral therapy. PMID:26968795

  4. Mitochondrial targeting of bilirubin regulatory enzymes: An adaptive response to oxidative stress.

    PubMed

    Muhsain, Siti Nur Fadzilah; Lang, Matti A; Abu-Bakar, A'edah

    2015-01-01

    The intracellular level of bilirubin (BR), an endogenous antioxidant that is cytotoxic at high concentrations, is tightly controlled within the optimal therapeutic range. We have recently described a concerted intracellular BR regulation by two microsomal enzymes: heme oxygenase 1 (HMOX1), essential for BR production and cytochrome P450 2A5 (CYP2A5), a BR oxidase. Herein, we describe targeting of these enzymes to hepatic mitochondria during oxidative stress. The kinetics of microsomal and mitochondrial BR oxidation were compared. Treatment of DBA/2J mice with 200mgpyrazole/kg/day for 3days increased hepatic intracellular protein carbonyl content and induced nucleo-translocation of Nrf2. HMOX1 and CYP2A5 proteins and activities were elevated in microsomes and mitoplasts but not the UGT1A1, a catalyst of BR glucuronidation. A CYP2A5 antibody inhibited 75% of microsomal BR oxidation. The inhibition was absent in control mitoplasts but elevated to 50% after treatment. An adrenodoxin reductase antibody did not inhibit microsomal BR oxidation but inhibited 50% of mitochondrial BR oxidation. Ascorbic acid inhibited 5% and 22% of the reaction in control and treated microsomes, respectively. In control mitoplasts the inhibition was 100%, which was reduced to 50% after treatment. Bilirubin affinity to mitochondrial and microsomal CYP2A5 enzyme is equally high. Lastly, the treatment neither released cytochrome c into cytoplasm nor dissipated membrane potential, indicating the absence of mitochondrial membrane damage. Collectively, the observations suggest that BR regulatory enzymes are recruited to mitochondria during oxidative stress and BR oxidation by mitochondrial CYP2A5 is supported by mitochondrial mono-oxygenase system. The induced recruitment potentially confers membrane protection. PMID:25478736

  5. Exome-Wide Association Study Identifies New Low-Frequency and Rare UGT1A1 Coding Variants and UGT1A6 Coding Variants Influencing Serum Bilirubin in Elderly Subjects

    PubMed Central

    Oussalah, Abderrahim; Bosco, Paolo; Anello, Guido; Spada, Rosario; Guéant-Rodriguez, Rosa-Maria; Chery, Céline; Rouyer, Pierre; Josse, Thomas; Romano, Antonino; Elia, Maurizzio; Bronowicki, Jean-Pierre; Guéant, Jean-Louis

    2015-01-01

    Abstract Genome-wide association studies (GWASs) have identified loci contributing to total serum bilirubin level. However, no exome-wide approaches have been performed to address this question. Using exome-wide approach, we assessed the influence of protein-coding variants on unconjugated, conjugated, and total serum bilirubin levels in a well-characterized cohort of 773 ambulatory elderly subjects from Italy. Coding variants were replicated in 227 elderly subjects from the same area. We identified 4 missense rare (minor allele frequency, MAF < 0.5%) and low-frequency (MAF, 0.5%–5%) coding variants located in the first exon of the UGT1A1 gene, which encodes for the substrate-binding domain (rs4148323 [MAF = 0.06%; p.Gly71Arg], rs144398951 [MAF = 0.06%; p.Ile215Val], rs35003977 [MAF = 0.78%; p.Val225Gly], and rs57307513 [MAF = 0.06%; p.Ser250Pro]). These variants were in strong linkage disequilibrium with 3 intronic UGT1A1 variants (rs887829, rs4148325, rs6742078), which were significantly associated with total bilirubin level (P = 2.34 × 10−34, P = 7.02 × 10−34, and P = 8.27 × 10−34), as well as unconjugated, and conjugated bilirubin levels. We also identified UGT1A6 variants in association with total (rs6759892, p.Ser7Ala, P = 1.98 × 10−26; rs2070959, p.Thr181Ala, P = 2.87 × 10−27; and rs1105879, p.Arg184Ser, P = 3.27 × 10−29), unconjugated, and conjugated bilirubin levels. All UGT1A1 intronic variants (rs887829, rs6742078, and rs4148325) and UGT1A6 coding variants (rs6759892, rs2070959, and rs1105879) were significantly associated with gallstone-related cholecystectomy risk. The UGT1A6 variant rs2070959 (p.Thr181Ala) was associated with the highest risk of gallstone–related cholecystectomy (OR, 4.58; 95% CI, 1.58–13.28; P = 3.21 × 10−3). Using an exome-wide approach we identified coding variants on UGT1A1 and UGT1A6 genes in association with serum bilirubin

  6. A new automated method for the determination of the Total Antioxidant Capacity (TAC) of human plasma, based on the crocin bleaching assay

    PubMed Central

    Kampa, Marilena; Nistikaki, Anastasia; Tsaousis, Vassilios; Maliaraki, Niki; Notas, George; Castanas, Elias

    2002-01-01

    Background Antioxidant molecules, which scavenge free radical species to prevent or delay oxidative damage of important macromolecules, membrane lipids and lipoproteins, are prevalent in plasma and other biological fluids. Among them, bilirubin, uric acid and protein thiols are the major endogenous antioxidants, while vitamins C and E, as well as a number of food-derived (poly)aromatic substances, belonging to stilbens, flavonoids and phenolic acids, are the main classes of nutritional antioxidants. Assays for total antioxidant capacity in plasma differ in their type of oxidation source, target and measurement used to detect the oxidized product. Methods In the present work we present an automated assay for the estimation of blood total antioxidant capacity (TAC assay), based on the crocin bleaching (oxidation) method. This method was adapted on a modern autoanalyzer, was linear over a wide range of values (0–3 mmol/L), and performed using an end point measurement. Results The TAC method presented a linear correlation with another automated commercial Total Antioxidant Status (TAS) test. Detection of the interference of different metabolites revealed a significant participation of TAC from uric acid, bilirubin, albumin, a minor interference from ascorbic acid, and no interference from hemoglobin. TAC was not modified by two freeze/thawing cycles, and was stable in samples stored at room temperature for 4 hours. K-EDTA and heparin were the best anticoagulants, while citrate decreased TAC by 20%. Reference values derived from samples of normal blood donors was 1.175 ± 0.007 mmol/L (mean ± SEM), while a diet rich in antioxidants more than doubled this value. Conclusions The proposed TAC assay, is fully automated, stable and reliable, and could be of value in the estimation of the AC of plasma. It is further proposed to calculate the antioxidant capacity of plasma after a subtraction of all interference deriving from endogenous and/or exogenous metabolites. The

  7. 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.

  8. Mechanisms of albumin uptake by proximal tubular cells.

    PubMed

    Brunskill, N

    2001-01-01

    The likely role of albumin in the induction tubulo-interstitial injury in proteinuria has stimulated considerable interest in the entry of albumin into the proximal tubule and its subsequent uptake by proximal tubular cells. Currently, there is considerable controversy over the degree of glomerular permeability to albumin. After filtration, however, albumin binds to megalin and cubulin, two giant receptors in the apical membrane of proximal tubular cells. Albumin is subsequently re-absorbed by proximal tubular cells by receptor-mediated endocytosis, a process subject to complex regulation. The interaction of albumin with proximal tubule cells also leads to the generation of intracellular signals. The understanding of these pathways may provide important insights into the pathogenesis of renal scarring in proteinuria. PMID:11158855

  9. Preoperative Body Mass Index, Blood Albumin and Triglycerides Predict Survival for Patients with Gastric Cancer

    PubMed Central

    Liu, Bin Zheng; Tao, Lin; Chen, Yun Zhao; Li, Xu Zhe; Dong, Yu Ling; Ma, Ya Jing; Li, Shu Gang; Li, Feng; Zhang, Wen Jie

    2016-01-01

    Background Gastric cancer (GC) is common and its prognosis is often poor due to difficulties in early diagnosis and optimal treatment strategies. TNM staging system is useful in predicting prognosis but only possible after surgery. Therefore, it is desirable to investigate prognostic factors/markers that may predict prognosis before surgery by which helps appropriate management decisions preoperatively. Methods A total of 320 GC patients were consecutively recruited from 2004 to 2013 and followed up for 127 months (10.6 years) after surgery. These patients’ were examined for body mass index (BMI) and blood levels of albumin, triglyceride, total cholesterol, low density lipoprotein cholesterol (LDL-C), and high density lipoprotein cholesterol (HDL-C). Kaplan-Meier method and log rank test were used to analyze long-term survival using the above potential risk markers. We first employed medians of these variables to reveal maximal potentials of the above prognostic predictors. Results Three major findings were obtained: (1) Preoperative BMI was positively correlated with albumin (r = 0.144, P<0.05) and triglyceride (r = 0.365, P<0.01), but negatively correlated with TNM staging (r = -0.265, P<0.05). Preoperative albumin levels were positively correlated with triglyceride (r = 0.173, P<0.05) but again, negatively correlated with TNM staging (r = -0.137, P<0.05); (2) Poor survival was observed in GC patients with lower levels of BMI (P = 0.028), albumin (P = 0.004), and triglyceride (P = 0.043), respectively. Receiver operating characteristic (ROC) curve analyses suggested BMI, albumin and triglyceride to have survival-predictor powers similar to TNM system; and (3) Cox multi-factorial analyses demonstrated that age (P = 0.049), BMI (P = 0.016), cell differentiation (P = 0.001), and TNM staging (P = 0.011) were independent overall survival-predictors for GC patients. Conclusions Preoperative BMI, albumin, and triglyceride levels are capable of predicting survival for

  10. A Novel Albumin Gene Mutation (R222I) in Familial Dysalbuminemic Hyperthyroxinemia

    PubMed Central

    Schoenmakers, Nadia; Moran, Carla; Campi, Irene; Agostini, Maura; Bacon, Olivia; Rajanayagam, Odelia; Schwabe, John; Bradbury, Sonia; Barrett, Timothy; Geoghegan, Frank; Druce, Maralyn; Beck-Peccoz, Paolo; O'Toole, Angela; Clark, Penelope; Bignell, Michelle; Lyons, Greta; Halsall, David; Gurnell, Mark

    2014-01-01

    Context: Familial dysalbuminemic hyperthyroxinemia, characterized by abnormal circulating albumin with increased T4 affinity, causes artefactual elevation of free T4 concentrations in euthyroid individuals. Objective: Four unrelated index cases with discordant thyroid function tests in different assay platforms were investigated. Design and Results: Laboratory biochemical assessment, radiolabeled T4 binding studies, and ALB sequencing were undertaken. 125I-T4 binding to both serum and albumin in affected individuals was markedly increased, comparable with known familial dysalbuminemic hyperthyroxinemia cases. Sequencing showed heterozygosity for a novel ALB mutation (arginine to isoleucine at codon 222, R222I) in all four cases and segregation of the genetic defect with abnormal biochemical phenotype in one family. Molecular modeling indicates that arginine 222 is located within a high-affinity T4 binding site in albumin, with substitution by isoleucine, which has a smaller side chain predicted to reduce steric hindrance, thereby facilitating T4 and rT3 binding. When tested in current immunoassays, serum free T4 values from R222I heterozygotes were more measurably abnormal in one-step vs two-step assay architectures. Total rT3 measurements were also abnormally elevated. Conclusions: A novel mutation (R222I) in the ALB gene mediates dominantly inherited dysalbuminemic hyperthyroxinemia. Susceptibility of current free T4 immunoassays to interference by this mutant albumin suggests likely future identification of individuals with this variant binding protein. PMID:24646103

  11. Relative rates of albumin equilibration in the skin interstitium and lymph during vasodilation

    SciTech Connect

    Powers, M.R.; Wallace, J.R.; Bell, D.R.

    1986-03-01

    The initial equilibration of /sup 125/I-labeled albumin between the vascular and extravascular compartments was studied in hindpaw skin of 6 anesthetized rabbits. Papavarine (200 ug/min) was infused into a small branch of the femoral artery of one limb with the contralateral limb as a control. There was a 1.2-fold increase in lymph flow (p < 0.01) with no significant change in the lymph-to-plasma total protein concentration ratio from prepopliteal lymphatics following papavarine. After reaching a constant, elevated lymph flow, tracer labeled albumin was infused to maintain the plasma activity constant for 3 hrs. The plasma volume in tissue samples was measured using /sup 131/I-labeled albumin injected 10 min before ending the experiment. Endogenous albumin was measured in plasma, lymph, and tissue samples using rocket electroimmunoassay. After 3 hrs of tracer infusion, lymph specific activity relative to plasma was significantly greater in the vasodilated hindlimb (0.30 +/- 0.07 vs 0.13 +/- 0.05; mean +/- SE; p < 0.01). Extravascular specific activity relative to plasma was greater in the vasodilated limb (0.13 +/- 0.02 vs 0.09 +/- 0.02; p < 0.05). Thus, vasodilation increased the rates at which lymph and tissue equilibrate with plasma. Also, the difference between lymph and tissue equilibration was greater in the vasodilated hindlimb.

  12. The thiol pool in human plasma: The central contribution of albumin to redox processes

    PubMed Central

    Turell, Lucía; Radi, Rafael; Alvarez, Beatriz

    2013-01-01

    The plasma compartment has particular features regarding the nature and concentration of low and high molecular weight thiols and oxidized derivatives. Plasma is relatively poor in thiol-based antioxidants; thiols are in lower concentrations than in cells and mostly oxidized. The different thiol-disulfide pairs are not in equilibrium and the steady-state concentrations of total thiols as well as reduced versus oxidized ratios are maintained by kinetic barriers, including the rates of reactions and transport processes. The single thiol of human serum albumin (HSA-SH) is the most abundant plasma thiol. It is an important target for oxidants and electrophiles due to its reactivity with a wide variety of species and its relatively high concentration. A relatively stable sulfenic (HSA-SO3H) acid can be formed in albumin exposed to oxidants. Plasma increases in mixed disulfides (HSA-SSR) or in sulfinic (HSA-SO2H) and sulfonic (HSA-SO3H) acids are associated with different pathologies and may constitute biomarkers of the antioxidant role of the albumin thiol. In this work we provide a critical review of the plasma thiol pool with a focus on human serum albumin. PMID:23747983

  13. 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.

  14. 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.

  15. Photoinduced conformational changes to porphyrin-bound albumin reduces albumin binding to Osteonectin

    NASA Astrophysics Data System (ADS)

    Rozinek, Sarah C.; Thomas, Robert J.; Brancaleon, Lorenzo

    2015-03-01

    Low intensity laser irradiation of photoactive ligands bound non-covalently to proteins can generate a structural change in the proteins, which is detectable spectroscopically. This light induced protein modification could help to study the structure/function relationship in proteins or to prompt non-native protein properties. That is, only if we can determine if and how protein function is effected. Much work has shown small light-induced secondary and tertiary structural changes to albumin have occurred when the protein is bound to a porphyrin such as protoporphyrin IX or meso-tetra(4- sulfonatophenyl)porphyrin (TSPP) and irradiated. This Affinity-Depletion study aims to explore the conformational change of TSPP-bound albumin after visible-light irradiation by testing its ability to bind the biologically relevant albumin receptor, osteonectin. Osteonectin has been covalently attached to magnetic beads, forming an affinity column, but after ten trials (of varied protocol) no substantial albumin-to-osteonectin binding could be achieved.

  16. Research on prevention of bilirubin-induced brain injury and kernicterus: National Institute of Child Health and Human Development conference executive summary. 2003.

    PubMed

    Blackmon, Lillian R; Fanaroff, Avroy A; Raju, Tonse N K

    2004-07-01

    In July 2003, the National Institute of Child Health and Human Development convened a conference, "Research on Prevention of Bilirubin-Induced Brain Injury and Kernicterus: Bench-to-Bedside." This article will provide a summary of presentations and discussions from this conference. The summary will focus on the identified knowledge gaps in 5 areas related to bilirubin-induced brain injury and kernicterus: 1) neurobiology and neuroimaging; 2) epidemiology and issues of clinical management; 3) methodologies for assessing clinical jaundice and direct and noninvasive measurement of serum bilirubin and hemolysis; 4) therapies for management of neonatal hyperbilirubinemia; and 5) public health surveillance and systems-based approaches to prevention. PMID:15231933

  17. Self-assembly of aqueous bilirubin ditaurate, a natural conjugated bile pigment, to contraposing enantiomeric dimers and M(-) and P(+) tetramers and their selective hydrophilic disaggregation by monomers and micelles of bile salts.

    PubMed

    Neubrand, Michael W; Carey, Martin C; Laue, Thomas M

    2015-02-24

    The solution behavior of bilirubin ditaurate (BDT), the first naturally occurring conjugated bile pigment to be physically and chemically characterized, was assessed in aqueous solution and in monomeric and micellar solutions of common taurine-conjugated bile salts (BS). Analytical ultracentrifugation revealed that BDT self-associates in monomer-dimer equilibria between 1 and 500 μM, forming limiting tetramers at low millimolar concentrations. Self-association was enthalpically driven with ΔG values of ≈5 kcal/mol, suggesting strong hydrophobic interactions. Added NaCl and decreases in temperature shifted the oligomerization to lower BDT concentrations. On the basis of circular dichroism spectra and the limiting size of the self-aggregates, we infer that the tetramers are composed of 2P(+) and 2M(-) enantiomeric BDT pairs in "ridge-tile" conformations interacting in a "double-bookend" structure. With added monomeric BS, blue shifts in the UV-vis spectra and tight isosbestic points revealed that BDT/BS heterodimers form, followed by BDT "decorating" BS micelles mostly via hydrophilic interactions. Conformational enantiomerism, fluorescence intensities, and anisotropy, as well as resistance of the hybrid particles to disaggregation in 6 M urea, suggested that two or three hydrogen-bonding sites bound BDT monomers to the hydroxyl groups of BS, possibly via pyrrole-π-orbital-OH interactions. BDT stabilized these interactions by enveloping the BS in its "ridge-tile" pincers with variable strain that maximized van der Waals interactions. Possibly because the BDT molecule becomes highly strained with BS subtending a 7β-hydroxyl group, BDT became totally resistant to oxidation in air. This work predicts that, because of BS dissolution of the BDT self-aggregates, BS/bilirubin hybrid particles, which are stabilized hydrophilically, are likely to be the dominant mode of transport for all conjugated bilirubins in bile. PMID:25671490

  18. Influence of saline infusion on blood-tissue albumin transport.

    PubMed

    Renkin, E M; Rew, K; Wong, M; O'Loughlin, D; Sibley, L

    1989-08-01

    Anesthetized rats were infused with lactated Ringer solution (LR) at constant rate for 30 or 60 min; delivered volume loads ranged from 0.03 to 0.08 ml/g body wt. Controls were given only a sustaining infusion of saline at 0.002 ml.g-1.h-1. Only 7-14% of the LR remained in the plasma at the end of the infusion; 76-88% entered the interstitial compartment, and 7-17% was excreted. The amount of plasma protein lost from the circulation with the extravasated fluid was studied simultaneously by two methods: 1) material balance in the whole animal and 2) changes in 131I-labeled albumin uptake (VA) and water content (VW) in individual tissues. The extravasation of 0.03-0.06 ml fluid/g body wt (75-160% initial plasma volume) did not significantly increase plasma protein extravasation in the whole rat. Nearly all of the sampled tissues of LR-infused rats had higher VW than controls. Tissue VA tended to increase with VW, but the regression slopes (delta VA/delta VW), a measure of the tracer albumin concentration of capillary filtrate relative to plasma, were low; skin, 0.006; paw, 0.018; skeletal muscles, 0.007; heart, 0.057; jejunum, 0.095; ileum, 0.045; cecum, 0.026; and colon, 0.027. These ratios are consistent with the very small loss of total plasma protein observed and attest to high solvent-drag reflection coefficients (sigma approximately equal to 1 - delta VA/delta VW): greater than 0.98 in capillaries of skeletal muscles, skin, and paw and 0.91-0.97 in heart and intestine. PMID:2764135

  19. 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.

  20. Binding and hydrolysis of soman by human serum albumin.

    PubMed

    Li, Bin; Nachon, Florian; Froment, Marie-Thérèse; Verdier, Laurent; Debouzy, Jean-Claude; Brasme, Bernardo; Gillon, Emilie; Schopfer, Lawrence M; Lockridge, Oksana; Masson, Patrick

    2008-02-01

    Human plasma and fatty acid free human albumin were incubated with soman at pH 8.0 and 25 degrees C. Four methods were used to monitor the reaction of albumin with soman: progressive inhibition of the aryl acylamidase activity of albumin, the release of fluoride ion from soman, 31P NMR, and mass spectrometry. Inhibition (phosphonylation) was slow with a bimolecular rate constant of 15 +/- 3 M(-1) min (-1). MALDI-TOF and tandem mass spectrometry of the soman-albumin adduct showed that albumin was phosphonylated on tyrosine 411. No secondary dealkylation of the adduct (aging) occurred. Covalent docking simulations and 31P NMR experiments showed that albumin has no enantiomeric preference for the four stereoisomers of soman. Spontaneous reactivation at pH 8.0 and 25 degrees C, measured as regaining of aryl acylamidase activity and decrease of covalent adduct (pinacolyl methylphosphonylated albumin) by NMR, occurred at a rate of 0.0044 h (-1), indicating that the adduct is quite stable ( t1/2 = 6.5 days). At pH 7.4 and 22 degrees C, the covalent soman-albumin adduct, measured by MALDI-TOF mass spectrometry, was more stable ( t1/2 = 20 days). Though the concentration of albumin in plasma is very high (about 0.6 mM), its reactivity with soman (phosphonylation and phosphotriesterase activity) is too slow to play a major role in detoxification of the highly toxic organophosphorus compound soman. Increasing the bimolecular rate constant of albumin for organophosphates is a protein engineering challenge that could lead to a new class of bioscavengers to be used against poisoning by nerve agents. Soman-albumin adducts detected by mass spectrometry could be useful for the diagnosis of soman exposure. PMID:18163544

  1. Determinants of formation of aflatoxin-albumin adducts: a seven-township study in Taiwan

    PubMed Central

    Sun, C-A; Wu, D-M; Wang, L-Y; Chen, C-J; You, S-L; Santella, R M

    2002-01-01

    Dietary exposure to aflatoxins is one of the major risk factors for hepatocellular carcinoma. Individual susceptibility to aflatoxin-induced hepatocarcinogenesis may be modulated by both genetic and environmental factors affecting metabolism. A cross-sectional study was performed to evaluate determinants of the formation of aflatoxin covalently bound to albumin (AFB1-albumin adducts). A total of 474 subjects who were free of liver cancer and cirrhosis and were initially selected as controls for previous case–control studies of aflatoxin-induced hepatocarcinogenesis in Taiwan, were employed in this study. Aflatoxin-albumin adducts were determined by competitive enzyme-linked immunosorbent assay, hepatitis B surface antigen and antibodies to hepatitis C virus by enzyme immunoassay, as well as genotypes of glutathione S-transferase M1-1 and T1-1 by polymerase chain reaction. The detection rate of AFB1-albumin adducts was significantly higher in males (42.5%) than in females (21.6%) (multivariate-adjusted odds ratio=2.6, 95% confidence interval=1.4–5.0). The formation of detectable albumin adducts was moderately higher in hepatitis B surface antigen carriers (42.8%) than in non-carriers (36.6%) (multivariate-adjusted odds ratio=1.4, 95% confidence interval=1.0–2.1). In addition, the detection rate of AFB1-albumin adducts tended to increase with the increasing number of null genotypes of glutathione S-transferase M1-1 and glutathione S-transferase T1-1. In conclusion, this cross-sectional study has assessed the relative contributions of environmental exposure and host susceptibility factors in the formation of AFB1-albumin adducts in a well characterised Chinese adult population. This study further emphasises the necessity to reduce aflatoxin exposure in people living in an area endemic for chronic hepatitis B virus infection. British Journal of Cancer (2002) 87, 966–970. doi:10.1038/sj.bjc.6600584 www.bjcancer.com © 2002 Cancer Research UK PMID:12434285

  2. Bilirubin oxidase based enzymatic air-breathing cathode: Operation under pristine and contaminated conditions.

    PubMed

    Santoro, Carlo; Babanova, Sofia; Erable, Benjamin; Schuler, Andrew; Atanassov, Plamen

    2016-04-01

    The performance of bilirubin oxidase (BOx) based air breathing cathode was constantly monitored over 45 days. The effect of electrolyte composition on the cathode oxygen reduction reaction (ORR) output was investigated. Particularly, deactivation of the electrocatalytic activity of the enzyme in phosphate buffer saline (PBS) solution and in activated sludge (AS) was evaluated. The greatest drop in current density was observed during the first 3 days of constant operation with a decrease of ~60 μA cm(-2) day(-1). The rate of decrease slowed to ~10 μA cm(-2) day(-1) (day 3 to 9) and then to ~1.5 μA cm(-2)day(-1) thereafter (day 9 to 45). Despite the constant decrease in output, the BOx cathode generated residual current after 45 days operations with an open circuit potential (OCP) of 475 mV vs. Ag/AgCl. Enzyme deactivation was also studied in AS to simulate an environment close to the real waste operation with pollutants, solid particles and bacteria. The presence of low-molecular weight soluble contaminants was identified as the main reason for an immediate enzymatic deactivation within few hours of cathode operation. The presence of solid particles and bacteria does not affect the natural degradation of the enzyme. PMID:26544631

  3. Rethinking the immune properties of bilirubin in viral hepatitis: from bench to bedside

    PubMed Central

    Corral-Jara, Karla F; Trujillo-Ochoa, Jorge L; Realpe, Mauricio; Panduro, Arturo; Roman, Sonia; Fierro, Nora A

    2015-01-01

    Communication between the immune system and metabolic components can be exemplified by the process of heme catabolism. The immunomodulatory functions of the enzymes, substrates and active products related to catabolism of the heme group have been extensively studied. Bilirubin (BR), the final breakdown product of heme, is primarily considered to be a toxic waste product but has recently been considered to be an immunomodulatory metabolite. Through mechanisms that include intracellular signaling and transcriptional control, BR affects those immune cell functions that regulate cell proliferation, differentiation and apoptosis. During the pathogenesis of viral hepatitis, the heme degradation pathway is disrupted, resulting in changes to normal BR concentrations. These alterations have been previously studied mainly as a consequence of the infection. However, little is known about the potential immunomodulatory role played by BR in the development of infectious hepatocellular diseases. Differences in BR levels in the context of viral hepatitis are likely to provide important insights into the metabolite-mediated mechanisms controlling the immune responses underlying both the long-term persistence of hepatitis C virus (HCV) infection and the resolution of hepatitis A virus (HAV) infection during the acute phase. In this review, the cross-talk between heme catabolism and immune function is described in detail. Special emphasis is given to discoveries that hold promise for identifying immunologic features of metabolic products in the resolution of viral diseases. PMID:26719800

  4. Development of a diagnostic system for bilirubin detection in cerebral spinal fluid

    NASA Astrophysics Data System (ADS)

    Bhadri, Prashant R.; Salgaonkar, Vasant A.; Majumdar, Anindya; Morgan, Chad J.; Zuccarello, Mario; Pyne, Gail J.; Dulaney, Elizabeth; Caffery, James, Jr.; Shukla, Rakesh; Beyette, Fred R., Jr.

    2004-11-01

    A weakened portion of an artery in the brain leads to a medical condition known as a cerebral aneurysm. A subarachnoid hemorrhage (SAH) occurs when an aneurysm ruptures. For those individuals suspected of having a SAH, a computerized tomography (CT) scan of the brain usually demonstrates evidence of the bleeding. However, in a considerable portion of people, the CT scan is unable to detect the blood that has escaped from the blood vessel. Recent studies have indicated nearly 30% of patients with a SAH are initially misdiagnosed. For circumstances when a SAH is suspected despite a normal CT scan, physicians make the diagnosis of SAH by performing a spinal tap. A spinal tap uses a needle to sample the cerebrospinal fluid (CSF) collected from the patient"s lumbar spine. However, it is also possible for blood to be introduced into the CSF as a result of the spinal tap procedure. Therefore, an effective solution is required to help medical personnel differentiate between the blood that results from a tap and that from a ruptured aneurysm. In this paper, the development of a prototype is described which is sensitive and specific for measuring bilirubin in CSF, hemorrhagic-CSF and CSF-like solutions. To develop this instrument a combination of spectrophotometric analysis, custom data analysis software and other hardware interfaces are assembled that lay the foundation for the development of portable and user-friendly equipment suitable for assisting trained medical personnel with the diagnosis of a ruptured cerebral aneurysm.

  5. Total protein

    MedlinePlus

    The total protein test measures the total amount of two classes of proteins found in the fluid portion of your ... nutritional problems, kidney disease or liver disease . If total protein is abnormal, you will need to have more ...

  6. Total protein

    MedlinePlus

    ... page: //medlineplus.gov/ency/article/003483.htm Total protein To use the sharing features on this page, please enable JavaScript. The total protein test measures the total amount of two classes ...

  7. [Pulsed radiolysis of aqueous solutions of serum albumin containing naphthoquinones].

    PubMed

    Pribush, A G; Savich, A V

    1987-01-01

    As was shown by the pulse radiolysis method the simultaneous presence of naphthoquinone and human serum albumin molecules in an aqueous solution leads to the adsorption of the former on the surface of the latter. It is suggested that in these conditions the protein tertiary structure changes. New conformation reduces the reactivity of albumin toward the hydrated electron. PMID:3628723

  8. Facile cell patterning on an albumin-coated surface.

    PubMed

    Yamazoe, Hironori; Uemura, Toshimasa; Tanabe, Toshizumi

    2008-08-19

    Fabrication of micropatterned surfaces to organize and control cell adhesion and proliferation is an indispensable technique for cell-based technologies. Although several successful strategies for creating cellular micropatterns on substrates have been demonstrated, a complex multistep process and requirements for special and expensive equipment or materials limit their prevalence as a general experimental tool. To circumvent these problems, we describe here a novel facile fabrication method for a micropatterned surface for cell patterning by utilizing the UV-induced conversion of the cell adhesive property of albumin, which is the most abundant protein in blood plasma. An albumin-coated surface was prepared by cross-linking albumin with ethylene glycol diglycidyl ether and subsequent casting of the cross-linked albumin solution on the cell culture dish. While cells did not attach to the albumin surface prepared in this way, UV exposure renders the surface cell-adhesive. Thus, surface micropatterning was achieved simply by exposing the albumin-coated surface to UV light through a mask with the desired pattern. Mouse fibroblast L929 cells were inoculated on the patterned albumin substrates, and cells attached and spread in a highly selective manner according to the UV-irradiated pattern. Although detailed investigation of the molecular-level mechanism concerning the change in cell adhesiveness of the albumin-coated surface is required, the present results would give a novel facile method for the fabrication of cell micropatterned surfaces. PMID:18627191

  9. Investigation of bovine serum albumin glycation by THz spectroscopy

    NASA Astrophysics Data System (ADS)

    Cherkasova, Olga P.; Nazarov, Maxim M.; Shkurinov, Alexander P.

    2016-04-01

    Protein glycation is accelerated under hyperglycemic conditions resulting to loss in the structure and biological functions of proteins. The transmission THz spectroscopy has been used for measuring of bovine serum albumin glycation dynamics. It was found that amplitude of albumin THz absorption depends on type of sugars and incubation time.

  10. 21 CFR 866.5040 - Albumin immunological test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Albumin immunological test system. 866.5040 Section 866.5040 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... other body fluids. Measurement of albumin aids in the diagnosis of kidney and intestinal diseases....

  11. 21 CFR 866.5040 - Albumin immunological test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Albumin immunological test system. 866.5040 Section 866.5040 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... other body fluids. Measurement of albumin aids in the diagnosis of kidney and intestinal diseases....

  12. 21 CFR 866.5040 - Albumin immunological test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Albumin immunological test system. 866.5040 Section 866.5040 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... other body fluids. Measurement of albumin aids in the diagnosis of kidney and intestinal diseases....

  13. 21 CFR 866.5040 - Albumin immunological test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Albumin immunological test system. 866.5040 Section 866.5040 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... other body fluids. Measurement of albumin aids in the diagnosis of kidney and intestinal diseases....

  14. Research Advances. Image Pinpoints All 5 Million Atoms in Viral Coat; Bilirubin, "Animals-Only" Pigment, Found in Plants; New Evidence Shows Humans Make Salicylic Acid

    NASA Astrophysics Data System (ADS)

    King, Angela G.

    2009-08-01

    Recent "firsts" in chemical research: image of a viral capsid pinpointing 5 million atoms; isolation and identification of an "animal" pigment, bilirubin, from a plant source; evidence that humans make salicylic acid.

  15. Bilirubin removal from human plasma by Cibacron Blue F3GA using immobilized microporous affinity membranous capillary method.

    PubMed

    Zhang, Lei; Jin, Gu

    2005-07-01

    A novel affinity sorbent system for direct bilirubin removal from human plasma was developed. These new adsorbents comprise Cibacron Blue F3GA as the specific ligand, and microporous membranous poly(tetrafluoroethylene) capillary (modified by coating with a hydrophilic layer of poly(vinyl alcohol) after activation) as the carrier matrix. The affinity adsorbents carrying 126.5 micromol Cibacron Blue F3GA/g polymer was then used to remove bilirubin in a flow-injection system. Non-specific adsorption on the poly(vinyl alcohol) coated capillary remains low, and higher affinity adsorption capacity, of up to 76.2 mg/g polymer was obtained after dye immobilization. The bilirubin adsorption capacity of the affinity capillary decreased with increase in the recirculation rate of plasma. The adsorption capacity increased with increase the temperature while decreased with increase the ionic strength. The maximum adsorption was only observed in neutral solution (pH 6-7). The adsorption isotherm fitted the Langmuir model well. These new adsorbents have higher velocity of mass transfer, better adsorption capacity, less fouling, longer service life and good reusability. The results of blood tests suggested the dye affinity capillary has good blood compatibility. PMID:15894520

  16. Dimethyl ester of bilirubin exhibits anti-inflammatory activity through inhibition of secretory phospholipase A2, lipoxygenase and cyclooxygenase.

    PubMed

    Joshi, Vikram; Umashankara, M; Ramakrishnan, Chandrasekaran; Nanjaraj Urs, Ankanahalli N; Suvilesh, Kanve Nagaraj; Velmurugan, Devadasan; Rangappa, Kanchugarakoppal S; Vishwanath, Bannikuppe Sannanaik

    2016-05-15

    Overproduction of arachidonic acid (AA) mediated by secretory phospholipase A2 group IIA (sPLA2IIA) is a hallmark of many inflammatory disorders. AA is subsequently converted into pro-inflammatory eicosanoids through 5-lipoxygenase (5-LOX) and cyclooxygenase-1/2 (COX-1/2) activities. Hence, inhibition of sPLA2IIA, 5-LOX and COX-1/2 activities is critical in regulating inflammation. We have previously reported unconjugated bilirubin (UCB), an endogenous antioxidant, as sPLA2IIA inhibitor. However, lipophilic UCB gets conjugated in liver with glucuronic acid into hydrophilic conjugated bilirubin (CB). Since hydrophobicity is pre-requisite for sPLA2IIA inhibition, conjugation reduces the efficacy of UCB. In this regard, UCB was chemically modified and derivatives were evaluated for sPLA2IIA, 5-LOX and COX-1/2 inhibition. Among the derivatives, BD1 (dimethyl ester of bilirubin) exhibited ∼ 3 fold greater inhibitory potency towards sPLA2IIA compared to UCB. Both UCB and BD1 inhibited human 5-LOX and COX-2 activities; however only BD1 inhibited AA induced platelet aggregation. Molecular docking studies demonstrated BD1 as better inhibitor of aforesaid enzymes than UCB and other endogenous antioxidants. These data suggest that BD1 exhibits strong anti-inflammatory activity through inhibition of AA cascade enzymes which is of great therapeutic importance. PMID:27060751

  17. Liver function tests and urinary albumin in house painters with previous heavy exposure to organic solvents.

    PubMed

    Lundberg, I; Nise, G; Hedenborg, G; Högberg, M; Vesterberg, O

    1994-05-01

    The serum activities or concentrations of aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), alkaline phosphatase (ALP), albumin, gamma-glutamyl transpeptidase (GGT), bilirubin (BIL), cholic acid (CHOL), chenodeoxycholic acid (CHENO), and transferrin with isoelectric point 5.7, and the urinary excretion of albumin were determined among male current or former house painters (n = 135) and house carpenters (n = 71) who had worked in their trades for at least 10 years before 1970. Workers who showed a value above the 90th percentile among the carpenters in at least one of the tests ASAT, ALAT, GGT, BIL, CHOL, or CHENO were regarded as showing "possible signs of liver dysfunction". Each participant's lifetime solvent exposure was evaluated by interview. The painters were divided into categories with low, intermediate, and heavy cumulative exposure during life (LTSE) or during the most exposed year (MEYSE). All participants stated none or slight recent exposure. The prevalence of possible signs of liver dysfunction increased with solvent exposure category according to LTSE as well as MEYSE with a numerically higher risk estimate in the heavy exposure category for MEYSE than for LTSE. ALP activity increased with exposure category according to both exposure estimates. This increase seemed to be due to an interaction between exposure to solvents and current or previous long term intake of medicines potentially toxic to the liver. None of these results was affected by whether or not the subjects had been exposed to solvents during the year before the investigation. The exposure to solvents was not significantly related to any other outcome variable. It is concluded that long term heavy exposure to solvents may elicit changes in conventional liver function tests indicative of a mild chronic effect on the liver. The findings also suggest that heavy solvent exposure during short time periods is a more likely cause of the findings than lifetime cumulative

  18. Albumin adsorption on to aluminium oxide and polyurethane surfaces.

    PubMed

    Sharma, C P; Sunny, M C

    1990-05-01

    The changes in protein adsorption onto aluminium surfaces coated with different thicknesses of oxide layers were examined. The oxide layers on aluminium substrates were derived by the anodizing technique. Protein adsorption studies were conducted using 125I-labelled albumin and the amount of albumin adsorbed was estimated with the help of a gamma counter. An increase in albumin adsorption was observed on oxide layer coated aluminium surfaces. The effect of anti-Hageman factor on albumin and fibrinogen adsorption on to bare aluminium, oxide layer coated aluminium and bare polyether urethane urea surfaces was also investigated. It was observed that the presence of anti-Hageman factor increased the adsorption of albumin and fibrinogen on to all these substrates. PMID:2383620

  19. 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.

  20. 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. PMID:26776001

  1. Application of high-performance liquid chromatography combined with ultra-sensitive thermal lens spectrometric detection for simultaneous biliverdin and bilirubin assessment at trace levels in human serum.

    PubMed

    Martelanc, Mitja; Žiberna, Lovro; Passamonti, Sabina; Franko, Mladen

    2016-07-01

    We present the applicability of a new ultra-sensitive analytical method for the simultaneous determination of biliverdin and bilirubin in human serum. The method comprises isocratic reversed-phase (RP) C18 high-performance liquid chromatography (HPLC) and thermal lens spectrometric detection (TLS) based on excitation by a krypton laser emission line at 407nm. This method enables the separation of IX-α biliverdin and IX-α bilirubin in 11min with limit of detection (LOD) and limit of quantitation (LOQ) for biliverdin of 1.2nM and 3nM, and 1nM and 2.8nM for bilirubin, respectively. In addition, a step-gradient elution was set up, by changing the mobile phase composition, in order to further enhance the sensitivity for bilirubin determination with LOD and LOQ of 0.5nM and 1.5nM, respectively. In parallel, an isocratic HPLC-DAD method was developed for benchmarking against HPLC-TLS methods. The LOD and LOQ for biliverdin were 6nM and 18nM, and 2.5nM and 8nM for bilirubin, respectively. Additionally, both isocratic methods were applied for measuring biliverdin and free bilirubin in human serum samples (from 2 male and 2 female healthy donors). Combining isocratic HPLC method with TLS detector was crucial for first ever biliverdin determination in serum together with simultaneous free bilirubin determination. We showed for the first time the concentration ratio of free bilirubin versus unbound biliverdin in human serum samples. PMID:27154653

  2. Apoptosis in murine hepatoma hepa 1c1c7 wild-type, C12, and C4 cells mediated by bilirubin.

    PubMed

    Seubert, John M; Darmon, Alison J; El-Kadi, Ayman O S; D'Souza, Sudhir J A; Bend, John R

    2002-08-01

    Elevated serum and tissue bilirubin concentrations that occur in pathological conditions such as cholestasis, jaundice, and other liver diseases are known to stimulate cytotoxic responses. In preliminary studies, we noted that bilirubin seemed to cause apoptosis in murine hepatoma Hepa 1c1c7 wild-type (WT) cells. Consequently, we investigated apoptosis caused by bilirubin in WT, mutant C12 [aryl hydrocarbon receptor (AHR)-deficient], and C4 (AHR nuclear translocator-deficient) Hepa 1c1c7 cells. Three independent measures of apoptosis were used to quantify the effects of exogenous bilirubin (0, 1, 10, 25, 50, or 100 microM). Caspase-3 activity and cytochrome c release from mitochondria increased at 3 h post-treatment, before increased caspase-8 activity at 6 h, and nuclear condensation by 24 h after treatment with bilirubin. No differences in whole-cell lipid peroxidation were observed between the cell types; however, intracellular reactive oxygen species (ROS) production was greater in WT cells than C12 or C4 cells 3 h after bilirubin exposure. Pretreatment of cells for 1 h with 1 or 10 microM alpha-naphthoflavone, an AHR antagonist, before bilirubin exposure resulted in decreased caspase-3 activity at 6 h and nuclear condensation at 24 h in WT cells. These results indicate that bilirubin, a potential AHR ligand, causes apoptosis in murine Hepa 1c1c7 WT cells by a mechanism(s) partially involving the AHR, disruption of membrane integrity, and increased intracellular ROS production. PMID:12130676

  3. Impairment of enzymatic antioxidant defenses is associated with bilirubin-induced neuronal cell death in the cerebellum of Ugt1 KO mice

    PubMed Central

    Bortolussi, G; Codarin, E; Antoniali, G; Vascotto, C; Vodret, S; Arena, S; Cesaratto, L; Scaloni, A; Tell, G; Muro, A F

    2015-01-01

    Severe hyperbilirubinemia is toxic during central nervous system development. Prolonged and uncontrolled high levels of unconjugated bilirubin lead to bilirubin-induced encephalopathy and eventually death by kernicterus. Despite extensive studies, the molecular and cellular mechanisms of bilirubin toxicity are still poorly defined. To fill this gap, we investigated the molecular processes underlying neuronal injury in a mouse model of severe neonatal jaundice, which develops hyperbilirubinemia as a consequence of a null mutation in the Ugt1 gene. These mutant mice show cerebellar abnormalities and hypoplasia, neuronal cell death and die shortly after birth because of bilirubin neurotoxicity. To identify protein changes associated with bilirubin-induced cell death, we performed proteomic analysis of cerebella from Ugt1 mutant and wild-type mice. Proteomic data pointed-out to oxidoreductase activities or antioxidant processes as important intracellular mechanisms altered during bilirubin-induced neurotoxicity. In particular, they revealed that down-representation of DJ-1, superoxide dismutase, peroxiredoxins 2 and 6 was associated with hyperbilirubinemia in the cerebellum of mutant mice. Interestingly, the reduction in protein levels seems to result from post-translational mechanisms because we did not detect significant quantitative differences in the corresponding mRNAs. We also observed an increase in neuro-specific enolase 2 both in the cerebellum and in the serum of mutant mice, supporting its potential use as a biomarker of bilirubin-induced neurological damage. In conclusion, our data show that different protective mechanisms fail to contrast oxidative burst in bilirubin-affected brain regions, ultimately leading to neurodegeneration. PMID:25950469

  4. A 25-year experience with total portosystemic shunts and reappraisal of colon exclusion.

    PubMed

    Talman, E A; Johns, T N; Regan, W W

    1983-05-01

    The results of 43 total shunt procedures for bleeding esophageal varices performed consecutively at two community hospitals from 1956 to 1981 are reviewed. Of 15 patients with immediate preoperative bilirubins greater than 2.0 mg/dl, 11 died following shunt surgery. Of 28 other shunted patients with immediate preoperative bilirubins of less than 2.0 mg/dl, there was only one in-hospital death, thus substantiating the contention that the last preoperative serum bilirubin value is the best predictor of operative mortality. Of ten patients with appreciable ascites verified at the time of operation, there were only two survivors, and both of these had preoperative bilirubins of less than 2.0 mg/dl. Twenty-nine of the 31 patients who left the hospital were still living at least one year after operation. All 23 patients operated on prior to 1977 were available for 5-year follow-up, and there were 14 survivors (60%). Thirteen of the 31 patients (42%) manifested some degree of hepatic encephalopathy, as interpreted by necessity for protein restriction and either Neomycin or Lactulose. Incapacitating post-shunt hepatic encephalopathy developed in one patient who required recurrent hospitalizations for episodic coma. This patient underwent a total abdominal colectomy and ileorectal anastomosis, with elimination of all episodes of encephalopathy for the subsequent 4 1/2 years. The previous 16 cases in the literature of surgical treatment of post-shunt encephalopathy are reviewed, and the efficacy of such colon exclusion is reassessed. PMID:6601935

  5. Biliverdin reductase/bilirubin mediates the anti-apoptotic effect of hypoxia in pulmonary arterial smooth muscle cells through ERK1/2 pathway

    SciTech Connect

    Song, Shasha; Wang, Shuang; Ma, Jun; Yao, Lan; Xing, Hao; Zhang, Lei; Liao, Lin; Zhu, Daling

    2013-08-01

    Inhibition of pulmonary arterial smooth muscle cell (PASMC) apoptosis induced by hypoxia plays an important role in pulmonary arterial remodeling leading to aggravate hypoxic pulmonary arterial hypertension. However, the mechanisms of hypoxia acting on PASMC apoptosis remain exclusive. Biliverdin reductase (BVR) has many essential biologic roles in physiological and pathological processes. Nevertheless, it is unclear whether the hypoxia-induced inhibition on PASMC apoptosis is mediated by BVR. In the present work, we found BVR majorly localized in PASMCs and was up-regulated in levels of protein and mRNA by hypoxia. Then we studied the contribution of BVR to anti-apoptotic response of hypoxia in PASMCs. Our results showed that siBVR, blocking generation of bilirubin, reversed the effect of hypoxia on enhancing cell survival and apoptotic protein (Bcl-2, procasepase-9, procasepase-3) expression, preventing nuclear shrinkage, DNA fragmentation and mitochondrial depolarization in starved PASMCs, which were recovered by exogenous bilirubin. Moreover, the inhibitory effect of bilirubin on PASMC apoptosis under hypoxic condition was blocked by the inhibitor of ERK1/2 pathway. Taken together, our data indicate that BVR contributes to the inhibitory process of hypoxia on PASMC apoptosis, which is mediated by bilirubin through ERK1/2 pathway. Highlights: • BVR expresses in PASMC and is up-regulated by hypoxia in protein and mRNA levels. • BVR/bilirubin contribute to the inhibitive process of hypoxia on PASMC apoptosis. • Bilirubin protects PASMC from apoptosis under hypoxia via ERK1/2 pathway.

  6. The effect of the initial reactant molar ratio and doping with Fe3+ on the formation of calcium bilirubinate in water-oil microemulsions

    NASA Astrophysics Data System (ADS)

    Liu, Siyun; Zhu, Jinmiao; Shen, Yuhua; Xie, Anjian; Zhang, Chunyan; Qiu, Lingguang

    2007-07-01

    A series of calcium bilirubinate nanoparticles were synthesized in microemulsions consisting of polyoxyethylene octylphenol ether (Triton X-100), n-hexyl alcohol (n-C6H13OH), cyclohexane (c-C6H12), and an aqueous solution. The particles were characterized by Fourier transform infrared (FT-IR) spectra, powder X-ray diffraction (XRD), inductively coupled plasma atomic emission spectrometry (ICP-AES), transmission electron microscopy (TEM), and zeta potential measurements. The results showed that the initial CaCl2/Na2BR molar ratio and the molar ratio of water to surfactant (ω0) influenced the morphology and microstructure of calcium bilirubinate nanoparticles and the sites of Ca2+ coordination to BR2-. The composition of synthesized calcium bilirubinate was nonstoichiometric. The stability of calcium bilirubinate nanoparticles dispersed in water changes as the Ca2+/BR2- molar ratio and solution pH varied. Dopant Fe2+ ions played a certain role in the simulated mineralization of calcium bilirubinate. A possible mechanism of calcium bilirubinate formation in inverse microemulsions is discussed.

  7. Early predictors of transplant-related mortality (TRM) after allogeneic bone marrow transplants (BMT): blood urea nitrogen (BUN) and bilirubin.

    PubMed

    Bacigalupo, A; Oneto, R; Bruno, B; Soracco, M; Lamparelli, T; Gualandi, F; Occhini, D; Raiola, A; Mordini, N; Berisso, G; Bregante, S; Dini, G; Lombardi, A; Lint, M V; Brand, R

    1999-09-01

    Transplant-related mortality (TRM) following allo- geneic bone marrow transplantation (BMT) remains a major concern and early identification of patients at risk may be clinically relevant. In this study we describe a predictive score based on bilirubin and blood urea nitrogen (BUN) levels on day +7 after BMT. The patient population consisted of 309 consecutive patients who underwent BMT from sibling (n = 263) or unrelated donors (n = 46) for hematologic disorders between December 1990 and December 1996. Of 27 laboratory tests taken on day +7 after BMT, serum bilirubin (P = 0.02) and BUN (P = 0.007) were found to be independent predictors of TRM in multivariate analysis. The median levels of bilirubin (0.9 mg/dl) and of BUN (21 mg/dl) were then used as a cut-off and a score of 1 was given for values equal/greater than the median. There were 216 patients with scores 0-1 (low risk) on day +7 (bilirubin <0.9 and/or BUN <21) and 93 patients with score 2 (high risk) (bilirubin >/=0.9 and BUN >/=21): the latter had more grade III-IV acute graft-versus-host disease (P = 0.03), slower neutrophil (P = 0.02) and slower platelet engraftment (P = 0.002). The actuarial 5 year TRM is 22% for low risk vs44% for high risk patients (P = 0.0003). For HLA-identical siblings TRM is 20% vs35% (P = 0.01), for unrelated donors it is 20% vs 65% (P = 0.01). Day +7 score was highly predictive of TRM on multivariate analysis (hazard ratio 1.9, P < 0.01), after adjustment for year of transplant (P < 0.00001), unrelated vs sibling donors (P = 0.001), patient age (P = 0.01) and diagnosis (P = 0.01). These results were validated on an independent group of 82 allogeneic BMT recipients in a pediatric Unit who showed an actuarial TRM of 16% for low risk vs 46% for high risk patients (P = 0.002). This study suggests that it may be possible to identify patients with different risks of TRM on day +7 after BMT: high risk patients could be eligible for programs designed to intensify prophylaxis of post

  8. Ameliorative Effect of Vanillic Acid on Serum Bilirubin, Chronotropic and Dromotropic Properties in the Cholestasis-Induced Model Rats

    PubMed Central

    Atefipour, Narges; Dianat, Mahin; Badavi, Mohammad; Sarkaki, Alireza

    2016-01-01

    Introduction The liver modulates several important roles, such as metabolism and liver cirrhosis, which have several cardiovascular problems. Due to preservative role of antioxidant agents in cardiovascular disease, consequently, many of them are applied as medicinal plants in traditional medicine. Vanillic acid (VA), as an antioxidant agent, has a principal preservative role on some diseases. In this study, the effect of vanillic acid was examined on heart rate (as chronotropic property), P-R interval (as dromotropic property), and serum bilirubin in cholestasis-induced model rats. Methods In this study, 32 male Sprague-Dawley rats weighing 200–250 g were allocated into four groups, and each group contained eight rats as follows: Control (normal saline, 1 ml/kg, gavage, daily for 4 weeks), cirrhotic (normal saline, 1 ml/kg, gavage, daily for 4 weeks), vanillic acid (10 mg/kg, gavage, daily for 4 weeks), cirrhotic treated with vanillic acid (10 mg/kg, gavage, daily for 4 weeks). Chronic biliary cirrhosis was induced in cirrhotic groups by four weeks Bile Duct Ligation (BDL). At the first day and four weeks after surgery, the animals were anesthetized, electrocardiograms were recorded (lead II), and chronotropic and dromotropic properties (HR and PR interval) were investigated. At the end of experimental duration, the animals were anesthetized, and blood samples were taken to measure serum bilirubin. The results were analyzed using t-test and one-way ANOVA by SPSS software, version 22. Results After induced of BDL, the results presented that laboratory parameter (bilirubin) in the cirrhotic group significantly increased compared to the control group. The P-R interval was reduced in the cirrhotic group compared to the control group, and there was no significant difference between heart rate in all groups. Bilirubin were reduced in cirrhotic groups treated with vanillic acid (VA) compared to cirrhotic group and also administration of VA in the cirrhotic treated with

  9. Radioactive excretion in human milk following administration of /sup 99m/Tc macroaggregated albumin

    SciTech Connect

    Pittard, W.B.; Merkatz, R.; Fletcher, B.D.

    1982-08-01

    Albumin-tagged sodium pertechnetate (technetium) is routinely used in nuclear medicine for scanning procedures of the lung. The rate of excretion of this radionuclide into breast milk and the resultant potential radiation hazard to the nursing infant have received little attention. Therefore the milk from a nursing mother who required a lung scan because of suspected pulmonary emboli using an intravenous injection of 4 mCi of /sup 99m/Tc macroaggregated human serum albumin was monitored. Albumin tagging severely limited the entrance of technetium into her milk and the radioactivity of the milk returned to base line by 24 hours. A total of 2.02 muCi of technetium was measured in the 24-hour milk collection after technetium injection and 94% of this amount was excreted by 15.5 hours. This amount of technetium administered orally to a newborn would deliver a total body radiation dose of .3 mrad. Therefore, an infant would receive trivial doses of radiation if breast-feeding were resumed 15.5 hours after administration of the radionuclide to the mother and nursing can clearly be resumed safely 24 hours after injection.

  10. ACCURACY OF SERUM - ASCITES ALBUMIN GRADIENT IN THE AETIOLOGICAL DIAGNOSIS OF ASCITES.

    PubMed

    Seth, A K; Rangarao, R; Pakhetra, R; Baskaran, V; Rana, Pvs; Rajamani, S

    2002-04-01

    50 adults with ascites admitted to our hospital were studied. Simultaneous samples of ascitic fluid and blood were collected and subjected to analysis including ascitic fluid total protein and serum ascites albumin gradient The cut off value of serum-ascites albumin gradient for differentiating between high and low gradient was taken as 1.1 gm % and of ascitic fluid protein for differentiating exudate and transudate as 2.5 gm%. The sensitivity, specificity, positive predictive value and negative predictive value of high gradient and transudative ascites in diagnosing portal hypertension were 943%, 60%, 84.6%, 81.8% and 62.9%, 133%, 91.7% and 50% respectively. High gradient ascites is a sensitive test in the diagnosis of portal hypertension as a cause of ascites. The exudate-transudate approach has severe limitations in the differential diagnosis of ascites. PMID:27407357

  11. Comparison of Albumin, Hydroxyethyl Starch and Ringer Lactate Solution as Priming Fluid for Cardiopulmonary Bypass in Paediatric Cardiac Surgery

    PubMed Central

    Prajapati, Mrugesh; Solanki, Atul; Pandya, Himani

    2016-01-01

    Introduction In paediatric cardiac surgery, there is still not any information with regard to the best choice of priming fluids for Cardiopulmonary Bypass (CPB). Albumin, Hydroxyethyl Starch (HES) & ringer lactate are equally used, but each has its advantages & disadvantages. Albumin & HES had better fluid balance which affect outcome in paediatric cardiac surgery significantly. Aim To compare priming solution containing albumin, hydroxyethyl starch and ringer lactate during elective open-heart surgery in paediatrics aged up to 3 years. Materials and Methods All patients were managed by standardized institution protocol and were randomly distributed into three groups based on the priming solution which is used in the CPB Circuit and having 35 patients in each group. Group A: Receive albumin 10 ml/kg in priming solution, Group B: Receive Hydroxyethyl starch (HES130/0.4) 6% 20ml/kg in priming solution, Group C: Receive ringer lactate priming solution. Primary outcome variable included perioperative haemoglobin, total protein, colloid osmotic pressure, platelets, fluid balance, urine output, post-operative blood loss, blood products usage, renal & liver function, extubation time, ICU stay & outcome. Results Patients receiving albumin had higher perioperative platelet count, total protein level & colloid osmotic pressure, lesser post-operative blood loss & blood products requirement. Patients receiving HES had lower level of platelets postoperatively than ringer lactate group but not associated with increase blood loss. HES did not affect renal function & haemostasis in this dose. Patients receiving ringer lactate had positive fluid balance intraoperatively. All three groups have similar effect on renal & liver function, urine output, time to extubation, ICU stay & outcome. Conclusion We conclude that albumin is expensive but better prime as maintain haemostasis, colloid oncotic pressure & reduced blood product requirement. HES will not hamper haemostasis & renal

  12. Heme Degradation by Heme Oxygenase Protects Mitochondria but Induces ER Stress via Formed Bilirubin

    PubMed Central

    Müllebner, Andrea; Moldzio, Rudolf; Redl, Heinz; Kozlov, Andrey V.; Duvigneau, J. Catharina

    2015-01-01

    Heme oxygenase (HO), in conjunction with biliverdin reductase, degrades heme to carbon monoxide, ferrous iron and bilirubin (BR); the latter is a potent antioxidant. The induced isoform HO-1 has evoked intense research interest, especially because it manifests anti-inflammatory and anti-apoptotic effects relieving acute cell stress. The mechanisms by which HO mediates the described effects are not completely clear. However, the degradation of heme, a strong pro-oxidant, and the generation of BR are considered to play key roles. The aim of this study was to determine the effects of BR on vital functions of hepatocytes focusing on mitochondria and the endoplasmic reticulum (ER). The affinity of BR to proteins is a known challenge for its exact quantification. We consider two major consequences of this affinity, namely possible analytical errors in the determination of HO activity, and biological effects of BR due to direct interaction with protein function. In order to overcome analytical bias we applied a polynomial correction accounting for the loss of BR due to its adsorption to proteins. To identify potential intracellular targets of BR we used an in vitro approach involving hepatocytes and isolated mitochondria. After verification that the hepatocytes possess HO activity at a similar level as liver tissue by using our improved post-extraction spectroscopic assay, we elucidated the effects of increased HO activity and the formed BR on mitochondrial function and the ER stress response. Our data show that BR may compromise cellular metabolism and proliferation via induction of ER stress. ER and mitochondria respond differently to elevated levels of BR and HO-activity. Mitochondria are susceptible to hemin, but active HO protects them against hemin-induced toxicity. BR at slightly elevated levels induces a stress response at the ER, resulting in a decreased proliferative and metabolic activity of hepatocytes. However, the proteins that are targeted by BR still have

  13. Heme oxygenase-1 induction prevents neuronal damage triggered during mitochondrial inhibition: role of CO and bilirubin.

    PubMed

    Orozco-Ibarra, Marisol; Estrada-Sánchez, Ana María; Massieu, Lourdes; Pedraza-Chaverrí, José

    2009-06-01

    Heme oxygenase (HO) catalyzes the breakdown of heme to iron, carbon monoxide (CO), and biliverdin, the latter being further reduced to bilirubin (BR). A protective role of the inducible isoform, HO-1, has been described in pathological conditions associated with reactive oxygen species (ROS) and oxidative damage. The aim of this study was to investigate the role of HO-1 in the neurotoxicity induced by the mitochondrial toxin 3-nitropropionic acid (3-NP) in primary cultures of cerebellar granule neurons (CGNs). Toxicity of 3-NP is associated with ROS production, and this metabolic toxin has been used to mimic pathological conditions such as Huntington's disease. We found that cell death caused by 3-NP exposure was exacerbated by inhibition of HO with tin mesoporphyrin (SnMP). In addition, HO-1 up-regulation induced by the exposure to cobalt protoporphyrin (CoPP) before the incubation with 3-NP, prevented the cell death and the increase in ROS induced by 3-NP. Interestingly, addition of SnMP to CoPP-pretreated CGNs exposed to 3-NP, abolished the protective effect of CoPP suggesting that HO activity was responsible for this protective effect. This was additionally supported by the fact that CORM-2, a CO-releasing molecule, and BR, were able to protect against cell death and the increase in ROS induced by 3-NP. Our data clearly show that HO-1 elicits in CGNs a neuroprotective action against the neurotoxicity of 3-NP and that CO and BR may be involved, at least in part, in this protective effect. The present results increase our knowledge about the role of HO-1 in neuropathological conditions. PMID:19063990

  14. Transport of nitrated albumin across continuous vascular endothelium

    PubMed Central

    Predescu, Dan; Predescu, Sanda; Malik, Asrar B.

    2002-01-01

    Because modification of plasma albumin on tyrosine residues generates nitrated albumin (NOA) that may function as a mechanism of nitrogen monoxide clearance from microcirculation, we investigated biochemicaly and morphologically the cell surface binding and the transendothelial transport of NOA. An electron microscopic study was carried out with mouse lungs and hearts perfused in situ with NOA and NOA-Au complexes. The results indicate that NOA-Au can bind to the endothelial cell surface, and its binding can be blocked by albumin plus nitrotyrosine (NO-tyrosine) or abolished by excess NOA. We detected NOA-Au into perivascular spaces as early as 30 sec after the beginning of its perfusion. NOA, unlike native albumin, leaves the vascular lumina via both endothelial caveolae and open junctions. By cross-linking and ligand blotting analysis, we showed that NOA interacted with the same albumin binding proteins of 16–18, 30–32, 60, and 74 kDa as native albumin. ELISA performed on tissue homogenates obtained from the same specimens showed that NOA transport was 2- to 4-fold greater than native albumin. The augmented transendothelial transport of NOA reflects its transcytosis as well as its exit from the microcirculation via open junctions. The increased transport of NOA may serve as an important mechanism that protects a vascular bed against the damaging effects of nitrogen monoxide and peroxynitrite. PMID:12370442

  15. 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.

  16. Albumin contributes to kidney disease progression in Alport syndrome.

    PubMed

    Jarad, George; Knutsen, Russell H; Mecham, Robert P; Miner, Jeffrey H

    2016-07-01

    Alport syndrome is a familial kidney disease caused by defects in the collagen type IV network of the glomerular basement membrane. Lack of collagen-α3α4α5(IV) changes the glomerular basement membrane morphologically and functionally, rendering it leaky to albumin and other plasma proteins. Filtered albumin has been suggested to be a cause of the glomerular and tubular injuries observed at advanced stages of Alport syndrome. To directly investigate the role that albumin plays in the progression of disease in Alport syndrome, we generated albumin knockout (Alb(-/-)) mice to use as a tool for removing albuminuria as a component of kidney disease. Mice lacking albumin were healthy and indistinguishable from control littermates, although they developed hypertriglyceridemia. Dyslipidemia was observed in Alb(+/-) mice, which displayed half the normal plasma albumin concentration. Alb mutant mice were bred to collagen-α3(IV) knockout (Col4a3(-/-)) mice, which are a model for human Alport syndrome. Lack of circulating and filtered albumin in Col4a3(-/-);Alb(-/-) mice resulted in dramatically improved kidney disease outcomes, as these mice lived 64% longer than did Col4a3(-/-);Alb(+/+) and Col4a3(-/-);Alb(+/-) mice, despite similar blood pressures and serum triglyceride levels. Further investigations showed that the absence of albumin correlated with reduced transforming growth factor-β1 signaling as well as reduced tubulointerstitial, glomerular, and podocyte pathology. We conclude that filtered albumin is injurious to kidney cells in Alport syndrome and perhaps in other proteinuric kidney diseases, including diabetic nephropathy. PMID:27147675

  17. 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.

  18. 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.

  19. The effects of Hespan on serum and lymphatic albumin, globulin, and coagulant protein.

    PubMed Central

    Lucas, C E; Denis, R; Ledgerwood, A M; Grabow, D

    1988-01-01

    The effects of hydroxyethyl starch (Hespan) resuscitation on serum and lymphatic proteins following hemorrhagic shock were studied in 34 splenectomized dogs. Following shock, five randomly assigned treatment groups received the shed blood plus 50 mL/kg of salt solution (RL) or RL with varying concentrations (0.22-1.5 gm/kg) of Hespan. Each dog received 50 ml/kg/d of the test solution for three days after shock. Prothrombin time, partial thromboplastin time, thrombin time, total serum protein, albumin, globulin, and coagulant protein activity of fibrinogen, prothrombin, and factor VIII were measured before shock, at the end of shock, following resuscitation, and on day 3; thoracic duct lymph values were obtained on day 3. Hespan-supplemented resuscitation lowered all serum proteins including albumin, globulin and coagulant proteins; concomitantly, the lymph protein rose after Hespan resuscitation. This decrease in serum proteins and rise in lymph proteins parallels similar results after albumin resuscitation in man and animals and suggests that Hespan induces an oncotically controlled extravascular protein relocation. Further studies on the significance of these findings need to be conducted. PMID:2451485

  20. Chromatographic removal and heat inactivation of hepatitis B virus during the manufacture of human albumin.

    PubMed

    Adcock, W L; MacGregor, A; Davies, J R; Hattarki, M; Anderson, D A; Goss, N H

    1998-10-01

    The purpose of the present study was to examine the efficacy of the chromatographic and pasteurization steps, employed in the manufacture of human albumin, in the removal and/or inactivation of hepatitis B virus (HBV). Most human albumins manufactured today are prepared from donor plasma by fractionation methods that use precipitation with cold ethanol. CSL Limited, an Australian biopharmaceutical company, has recently converted its method of manufacture for albumin from a traditional Cohn fractionation method to a method employing chromatographic techniques. A step-by-step validation of virus removal and inactivation was performed on this manufacturing process, which includes a DEAE-Sepharose(R) and CM-Sepharose(R) Fast Flow ion-exchange step, a Sephacryl(R) S200 High-Resolution gel-filtration step and a bulk pasteurization step where product is held at 60 degreesC for 10 h. HBV partitioning experiments were conducted on scaled-down chromatographic columns with hepatitis B surface antigen (HBsAg) as a marker, whereas the HBV model virus, duck HBV, was used to study the inactivation kinetics during pasteurization. Reductions for HBsAg through the three chromatographic steps resulted in a total log10 decrease of 1.5 log10, whereas more than 6.5 log10 decrease in duck HBV in Albumex(R)5 was achieved during pasteurization. PMID:9756468

  1. Cytochrome P450 2A5 and bilirubin: Mechanisms of gene regulation and cytoprotection

    SciTech Connect

    Kim, Sangsoo Daniel; Antenos, Monica; Squires, E. James; Kirby, Gordon M.

    2013-07-15

    Bilirubin (BR) has recently been identified as the first endogenous substrate for cytochrome P450 2A5 (CYP2A5) and it has been suggested that CYP2A5 plays a major role in BR clearance as an alternative mechanism to BR conjugation by uridine-diphosphate glucuronyltransferase 1A1. This study investigated the mechanisms of Cyp2a5 gene regulation by BR and the cytoprotective role of CYP2A5 in BR hepatotoxicity. BR induced CYP2A5 expression at the mRNA and protein levels in a dose-dependent manner in primary mouse hepatocytes. BR treatment also caused nuclear translocation of Nuclear factor-E2 p45-related factor 2 (Nrf2) in hepatocytes. In reporter assays, BR treatment of primary hepatocytes transfected with a Cyp2a5 promoter-luciferase reporter construct resulted in a 2-fold induction of Cyp2a5 reporter activity. Furthermore, cotransfection of the hepatocytes with a Nrf2 expression vector without BR treatment resulted in an increase in Cyp2a5 reporter activity of approximately 2-fold and BR treatment of Nrf2 cotransfectants further increased reporter activity by 4-fold. In addition, site-directed mutation of the ARE in the reporter construct completely abolished both the BR- and Nrf2-mediated increases in reporter activity. The cytoprotective role of CYP2A5 against BR-mediated apoptosis was also examined in Hepa 1–6 cells that lack endogenous CYP2A5. Transient overexpression of CYP2A5 partially blocked BR-induced caspase-3 cleavage in Hepa 1–6 cells. Furthermore, in vitro degradation of BR was increased by microsomes from Hepa 1–6 cells overexpressing CYP2A5 compared to control cells transfected with an empty vector. Collectively, these results suggest that Nrf2-mediated CYP2A5 transactivation in response to BR may provide an additional mechanism for adaptive cytoprotection against BR hepatotoxicity. - Highlights: • The mechanism of Cyp2a5 gene regulation by BR was investigated. • The cytoprotective role of CYP2A5 in BR hepatotoxicity was determined. • BR

  2. Importance of albumin binding in the assay for carnitine palmitoyltransferase.

    PubMed Central

    McCormick, K; Notar-Francesco, V J

    1983-01-01

    Alterations in the long-chain acyl-CoA binding to albumin in the carnitine palmitoyltransferase (CPT) assay appreciably affect the reaction at commonly used substrate concentrations. Since in the CPT assay the latter are typically well below saturation or Vmax. values, the measured enzyme activity depends on both the absolute quantity of albumin in the CPT assay and any biochemical modification of its binding. The present study verifies the striking dependence of the K0.5 for palmitoyl-CoA on albumin and the misleading 'activation' of the enzyme by compounds that also avidly bind to albumin. In assessing the intracellular physiological relevance of any modifier of CPT, the effects of protein binding in the assay assume particular importance. Indeed, any compound that alters CPT activity may do so, not directly, but as an assay artifact changing the free or unbound substrate concentrations. PMID:6661210

  3. 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.

  4. Development of FET-type albumin sensor for diagnosing nephritis.

    PubMed

    Park, Keun-Yong; Sohn, Young-Soo; Kim, Chang-Kyu; Kim, Hong-Seok; Bae, Young-Seuk; Choi, Sie-Young

    2008-07-15

    An albumin biosensor based on a potentiometric measurement using Biofield-effect-transistor (BioFET) has been designed and fabricated, and its characteristics were investigated. The BioFET was fabricated using semiconductor integrated circuit (IC) technology. The gate surface of the BioFET was chemically modified by newly developed self-assembled monolayer (SAM) synthesized by a thiazole benzo crown ether ethylamine (TBCEA)-thioctic acid to immobilize anti-albumin. SAM formation, antibody immobilization, and antigen-antibody interaction were verified using surface plasmon resonance (SPR). The output voltage changes of the BioFET with respect to various albumin concentrations were obtained. Quasi-reference electrode (QRE) and reference FET (ReFET) has been integrated with the BioFET, and its output characteristic was investigated. The results demonstrate the feasibility of the BioFET as the albumin sensor for diagnosing nephritis. PMID:18440216

  5. A high-capacity hydrophobic adsorbent for human serum albumin.

    PubMed

    Belew, M; Peterson, E A; Porath, J

    1985-12-01

    A simple method, based on salting out hydrophobic interaction chromatography, for the efficient removal of trace amounts of serum albumin from partially purified protein preparations is described. The method is also successfully applied for the purification of albumin from Cohn fraction IV, a by-product obtained from the commercial fractionation of human serum proteins by the ethanol precipitation procedure. About 70% of the adsorbed albumin can be eluted by buffer of low ionic strength and can thus be lyophilized directly, if required. The adsorbent can be used for several cycles of adsorption and desorption without affecting its selectivity or capacity. Its adsorption properties and capacity for serum albumin are compared with those of the commercially available adsorbent Blue Sepharose CL-6B. PMID:3879424

  6. Molecular interactions between albumin and proximal tubular cells.

    PubMed

    Brunskill, N J

    1998-01-01

    In glomerular diseases the filtration of excess proteins into the proximal tubule, together with their subsequent reabsorption may represent an important pathological mechanism underlying progressive renal scarring. The most prominent protein in glomerular filtrate, albumin, is reabsorbed by receptor-mediated endocytosis by proximal tubular cells. It binds both to scavenger-type receptors and to megalin in the proximal tubule. Some of these receptors appear to be shared with other cell types, particularly endothelial cells. The endocytic uptake of albumin is subjected to complex hormonal and enzymatic regulation. In addition to being reabsorbed in the proximal tubule, albumin may act as a signalling molecule in these cells, and may induce the expression of numerous pro-inflammatory genes. Modulation of the interaction of albumin with proximal tubular cells may eventually prove to be of therapeutic importance in the treatment of renal diseases. PMID:9807019

  7. Albumin microspheres for oral delivery of iron.

    PubMed

    Shivakumar, H N; Vaka, Siva Ram Kiran; Murthy, S Narasimha

    2010-01-01

    Bovine serum albumin (BSA) microspheres of ferric pyrophosphate (FPP) intended for passive targeting to the Peyer's patches has been proposed for oral iron supplementation. Microspheres prepared by emulsification chemical cross linking method were characterized for surface topography, entrapment efficiency, particle size, particle charge and in vitro drug release. Microspheres of batch C with FPP to BSA ratio of 1:5 were found to be most suitable for targeting as they exhibited high entrapment (83.88 +/- 4.31), high monodispersity (span = 1.24 +/- 0.01), and least particle size (d(vm) = 4.40 +/- 0.01). In addition the amount of iron retained in these microspheres despite exposure to simulated gastrointestinal conditions for 5 h was found to be 83.72 +/- 4.22%, the highest in the three batches. The in vivo serum iron profiles in normal rats following oral administration displayed a reduced T(max) (2 h), elevated C(max) (106.06 +/- 12.18 mug/dL) and increased AUC (0-16 h) (647.44 +/- 52.33 mug.h/dL) for these microspheres which significantly differed (P <0.05) from FPP solution indicating a higher iron repletion potential of the BSA microspheres. PMID:19635031

  8. 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

  9. In vivo albumin labeling and lymphatic imaging.

    PubMed

    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 ((18)F-AlF-NEB) and Evans blue (EB) dye. After local injection, both (18)F-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 (18)F-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 (18)F-AlF-NEB and EB has great potential for clinical application to map sentinel LNs and provide intraoperative guidance. PMID:25535368

  10. Complexes of dendrimers with bovine serum albumin.

    PubMed

    Mandeville, J S; Tajmir-Riahi, H A

    2010-02-01

    We report the complexation of bovine serum albumin (BSA) with several dendrimers of different compositions mPEG-PAMAM (G3), mPEG-PAMAM (G4), and PAMAM (G4) at physiological conditions using constant protein concentration and various dendrimer contents. FTIR, CD, and fluorescence spectroscopic methods were used to analyze polymer binding mode, the binding constant, and the effects of dendrimer complexation on BSA stability and conformation. Structural analysis showed that dendrimers bind BSA via hydrophilic and hydrophobic interactions with a number of bound polymers (n): 1.30 for mPEG-PAMAM-G3, 1.30 for mPEG-PAMAM-G4, and 1.0 for PAMAM-G4. The polymer-BSA binding constants were K(mPEG-G3) = 5.0 (+/-0.8) x 10(3) M(-1), K(mPEG-G4) = 1.0 (+/-0.3) x 10(4) M(-1), and K(PAMAM-G4) = 1.1 (+/-0.4) x 10(4) M(-1). Dendrimer binding altered BSA conformation with a major reduction of alpha-helix and an increase in random coil and turn structures, indicating a partial protein unfolding. PMID:20085247

  11. THE SECRETORY PATHWAYS OF RAT SERUM GLYCOPROTEINS AND ALBUMIN

    PubMed Central

    Redman, Colvin M.; Cherian, M. George

    1972-01-01

    These studies compare the secretory pathways of newly formed rat serum glycoproteins and albumin by studying their submicrosomal localization at early times after the beginning of their synthesis and also by determining the submicrosomal site of incorporation of N-acetylglucosamine, mannose, galactose, and leucine into protein. N-acetylglucosamine, mannose, and galactose were only incorporated in vitro into proteins from membrane-attached polysomes and not into proteins from free polysomes. Mannose incorporation occurred in the rough endoplasmic reticulum, was stimulated by puromycin but not by cycloheximide, and 90% of the mannose-labeled protein was bound to the membranes. Galactose incorporation, by contrast, occurred in the smooth microsome fraction and 89% of the radioactive protein was in the cisternae. Albumin was mostly recovered (98%) in the cisternae, with negligible amounts in the membranes. To determine whether the radio-active sugars were being incorporated into serum proteins or into membrane protein, the solubilized in vivo-labeled proteins were treated with specific antisera to rat serum proteins or to albumin. Immunoelectrophoresis of the 14C-labeled leucine membrane and cisternal proteins showed that the membranes contained radioactive serum glycoprotein but no albumin, while the cisternal fraction contained all of the radioactive albumin and some glycoproteins. The results indicate that newly formed serum glycoproteins remain attached to the membranes of the rough endoplasmic reticulum after they are released from the membrane-attached polysomes, while albumin passes directly into the cisternae. PMID:5057975

  12. Measurement of lung fluid volumes and albumin exclusion in sheep

    SciTech Connect

    Pou, N.A.; Roselli, R.J.; Parker, R.E.; Clanton, J.A.; Harris, T.R. )

    1989-10-01

    A radioactive tracer technique was used to determine interstitial diethylenetriaminepentaacetic acid (DTPA) and albumin distribution volume in sheep lungs. {sup 125}I- and/or {sup 131}I-labeled albumin were injected intravenously and allowed to equilibrate for 24 h. {sup 99m}Tc-labeled DTPA and {sup 51}Cr-labeled erythrocytes were injected and allowed to equilibrate (2 h and 15 min, respectively) before a lethal dose of thiamylal sodium. Two biopsies (1-3 g) were taken from each lung and the remaining tissue was homogenized for wet-to-dry lung weight and volume calculations. Estimates of distribution volumes from whole lung homogenized samples were statistically smaller than biopsy samples for extravascular water, interstitial {sup 99m}Tc-DTPA, and interstitial albumin. The mean fraction of the interstitium (Fe), which excludes albumin, was 0.68 +/- 0.04 for whole lung samples compared with 0.62 +/- 0.03 for biopsy samples. Hematocrit may explain the consistent difference. To make the Fe for biopsy samples match that for homogenized samples, a mean hematocrit, which was 82% of large vessel hematocrit, was required. Excluded volume fraction for exogenous sheep albumin was compared with that of exogenous human albumin in two sheep, and no difference was found at 24 h.

  13. Fluorescence lifetime measurements of native and glycated human serum albumin and bovine serum albumin

    NASA Astrophysics Data System (ADS)

    Joshi, Narahari V.; Joshi, Virgina O. d.; Contreras, Silvia; Gil, Herminia; Medina, Honorio; Siemiarczuk, Aleksander

    1999-05-01

    Nonenzymatic glycation, also known as Maillard reaction, plays an important role in the secondary complications of the diabetic pathology and aging, therefore, human serum albumin (HSA) and bovine serum albumin (BSA) were glycated by a conventional method in our laboratory using glucose as the glycating agent. Fluorescence lifetime measurements were carried out with a laser strobe fluorometer equipped with a nitrogen/dye laser and a frequency doubler as a pulsed excitation source. The samples were excited at 295 nm and the emission spectra were recorded at 345 nm. The obtained decay curves were tried for double and triple exponential functions. It has been found that the shorter lifetime increases for glycated proteins as compared with that of the native ones. For example, in the case of glycated BSA the lifetime increased from 1.36 ns to 2.30 ns. Similarly, for HSA, the lifetime increases from 1.58 ns to 2.26 ns. Meanwhile, the longer lifetime changed very slightly for both proteins (from 6.52 ns to 6.72 ns). The increase in the lifetime can be associated with the environmental effect; originated from the attachment of glucose to some lysine residues. A good example is Trp 214 which is in the cage of Lys 225, Lys 212, Lys 233, Lys 205, Lys 500, Lys 199 and Lys 195. If fluorescence lifetime technique is calibrated and properly used it could be employed for assessing glycation of proteins.

  14. Interaction of ergosterol with bovine serum albumin and human serum albumin by spectroscopic analysis.

    PubMed

    Cheng, Zhengjun

    2012-10-01

    This study was designed to examine the interactions of ergosterol with bovine serum albumin (BSA) and human serum albumin (HSA) under physiological conditions with the drug concentrations in the range of 2.99-105.88 μM and the concentration of proteins was fixed at 5.0 μM. The analysis of emission spectra quenching at different temperatures revealed that the quenching mechanism of HSA/BSA by ergosterol was the static quenching. The number of binding sites n and the binding constants K were obtained at various temperatures. The distance r between ergosterol and HSA/BSA was evaluated according to Föster non-radioactive energy transfer theory. The results of synchronous fluorescence, 3D fluorescence, FT-IR, CD and UV-Vis absorption spectra showed that the conformations of HSA/BSA altered in the presence of ergosterol. The thermodynamic parameters, free energy change (ΔG), enthalpy change (ΔH) and entropy change (ΔS) for BSA-ergosterol and HSA-ergosterol systems were calculated by the van't Hoff equation and discussed. Besides, with the aid of three site markers (for example, phenylbutazone, ibuprofen and digitoxin), we have reported that ergosterol primarily binds to the tryptophan residues of BSA/HSA within site I (subdomain II A). PMID:22733490

  15. Suggested mechanism for the selective excretion of glucosylated albumin. The effects of diabetes mellitus and aging on this process and the origins of diabetic microalbuminuria.

    PubMed

    Kowluru, A; Kowluru, R; Bitensky, M W; Corwin, E J; Solomon, S S; Johnson, J D

    1987-11-01

    In previous studies in the Sprague-Dawley rat, Williams and coworkers reported the phenomenon of selective urinary excretion of glucosylated albumin (editing, i.e., the percent glucosylation of urinary albumin is more than that of plasma albumin) by the mammalian kidney. Ghiggeri and coworkers subsequently found that the extent of editing is reduced in human diabetics. Moreover, the reduction in editing in diabetes correlates inversely with levels of microalbuminuria. We also find reduction in the extent of editing in diabetic humans. We find a striking inverse correlation not only with the magnitude of microalbuminuria but also with the extent of plasma albumin glucosylation. In contrast, we found little correlation between the reduction in editing and the duration of diabetes in human subjects. Stz induced diabetes in the Sprague-Dawley rat is associated with a striking and rapid reduction in editing which develops virtually with the same kinetics exhibited by the appearance of hyperglycemia. This loss of editing is rapidly reversed by daily administration of insulin but not by aldose reductase inhibitors. Mannitol infusion in anesthetized Wistar rats resulted in an increase in urine volume, GFR, and microalbuminuria, and was also accompanied by a marked reduction in editing. This reduction was rapidly reversed by a cessation of mannitol infusion. We propose here that glucosylated albumin (in contrast to unmodified albumin) is not reabsorbed by the proximal tubule, and thus, is preferentially excreted in the urine. We postulate that the increase in GFR which emerges as a consequence of increased plasma osmolality in diabetes mellitus delivers more albumin to the proximal tubule than can be reabsorbed. This results in a dilution of excreted glucosylated albumin molecules by excreted unmodified albumin, which appears as the early microscopic albuminuria of diabetes. Paradoxically, the fall in apparent editing is accompanied by an absolute increase in the total

  16. Coordinate secretion of mouse alphafetoprotein, mouse albumin and rat albumin by mouse hepatoma-rat hepatoma hybrid cells.

    PubMed

    Cassio, D; Hassoux, R; Dupiers, M; Uriel, J; Weiss, M C

    1980-09-01

    Mouse heptoma cells that secrete large amounts of alpha-fetoprotein (AFP) and albumin have been crossed with rat hepatoma cells that secret only albumin, and in relatively small amounts, to investigate the influence of each parental genome upon the expression of serum proteins. All of the ten independent hybrid clones examined produce mouse AFP and both mouse and rat albumin; none produces rat AFP. The absence of production of rat AFP by the hybrids suggests that different mechanisms are involved in the initiation and in the maintenance of expression of this function. The secretion of the three proteins by the hybrid cells is coordinate: Whatever the growth phase (exponential or stationary) and irrespective of the amounts produced over a wide range, the ratio secreted of mouse AFP to mouse albumin is near to one, and that of mouse albumin to rat albumin is near to five. In addition, even though the pattern of protein secretion during the growth cycle of hybrid cells is different from those of both parents, the products of both parental genomes conform to the new hybrid pattern. Finally, some hybrids secrete less of the proteins with increasing numbers of cell generations, yet all three continue to be secreted in coordinate fashion. Since the rates of secretion of serum proteins probably reflect their rates of synthesis, we conclude that coordinate secretion indicates coordinate synthesis, and may reflect coordinate transcription of the relevant genes. PMID:6158520

  17. Albumin concentration significantly impacts on free teicoplanin plasma concentrations in non-critically ill patients with chronic bone sepsis.

    PubMed

    Brink, A J; Richards, G A; Lautenbach, E E G; Rapeport, N; Schillack, V; van Niekerk, L; Lipman, J; Roberts, J A

    2015-06-01

    The impact of decreased serum albumin concentrations on free antibiotic concentrations in non-critically ill patients is poorly described. This study aimed to describe the pharmacokinetics of a high-dose regimen of teicoplanin, a highly protein-bound antibiotic, in non-critically ill patients with hypoalbuminaemia. Ten patients with chronic bone sepsis and decreased serum albumin concentrations (<35 g/L) receiving teicoplanin 12 mg/kg 12-hourly intravenously for 48 h followed by 12 mg/kg once daily were enrolled. Surgical debridement was performed on Day 3. Samples of venous blood were collected pre-infusion and post-infusion during the first 4 days of therapy. Total and free teicoplanin concentrations were assayed using validated chromatographic methods. The median serum albumin concentration for the cohort was 18 (IQR 15-24) g/L. After 48 h, the median (IQR) free trough (fC(min)) and total trough (tC(min)) concentrations were 2.90 (2.67-3.47) mg/L and 15.54 (10.28-19.12) mg/L, respectively, although trough concentrations declined thereafter. Clearance of the free concentrations was significantly high relative to the total fraction at 38.6 (IQR 29.9-47.8) L/h and 7.0 (IQR 6.8-9.8) L/h, respectively (P<0.001). Multiple linear regression analysis demonstrated that whereas total teicoplanin concentration did not impact on free concentrations (P=0.174), albumin concentration did (P<0.001). This study confirms the significant impact of hypoalbuminaemia on free concentrations of teicoplanin in non-critically ill patients, similar to that in critically ill patients. Furthermore, the poor correlation with total teicoplanin concentration suggests that therapeutic drug monitoring of free concentrations should be used in these patients. PMID:25819167

  18. Serum Albumin Levels and Economic Status in Japanese Older Adults

    PubMed Central

    Ota, Asami; Kondo, Naoki; Murayama, Nobuko; Tanabe, Naohito; Shobugawa, Yugo; Kondo, Katsunori

    2016-01-01

    Background Low serum albumin levels are associated with aging and medical conditions such as cancer, liver dysfunction, inflammation, and malnutrition and might be an independent predictor of long-term mortality in healthy older populations. We tested the hypothesis that economic status is associated with serum albumin levels and explained by nutritional and health status in Japanese older adults. Design We performed a cross-sectional analysis using data from the Japan Gerontological Evaluation study (JAGES). The study participants were 6528 functionally independent residents (3189 men and 3339 women) aged ≥65 years living in four municipalities in Aichi prefecture. We used household income as an indicator of economic status. Multiple linear regression was used to compare serum albumin levels in relation to household income, which was classified as low, middle, and high. Additionally, mediation by nutritional and health-related factors was analyzed in multivariable models. Results With the middle-income group as reference, participants with low incomes had a significantly lower serum albumin level, even after adjustment for sex, age, residential area, education, marital status, and household structure. The estimated mean difference was −0.17 g/L (95% confidence interval, −0.33 to −0.01 g/L). The relation between serum albumin level and low income became statistically insignificant when “body mass index”, “consumption of meat or fish”, “self-rated health”, “presence of medical conditions”, “hyperlipidemia”, or “respiratory disease “was included in the model. Conclusion Serum albumin levels were lower in Japanese older adults with low economic status. The decrease in albumin levels appears to be mediated by nutrition and health-related factors with low household incomes. Future studies are needed to reveal the existence of other pathways. PMID:27276092

  19. RBC-/Cr-51/ half-life and albumin turnover in growing Beagle dogs during chronic radial acceleration

    NASA Technical Reports Server (NTRS)

    Beckman, D. A.; Evans, J. W.; Oyama, J.

    1979-01-01

    The effects of chronic centrifugation on growing Beagle dogs exposed to -2 or -2.6 Gx on albumin and RBC turnover rates, albumin concentration and space, and total blood volume were determined and compared with caged and run control of animals. Albumin-(I-125) and autologous RBC-(Cr-51) preparations were injected into all dogs at day 82 of the centrifugation periods, and the disappearance curves were determined by successive bleedings of the animals over the next 35 d, during which the centrifugation was continued. There were no differences in albumin turnover rates or space. Two populations of RBCs were found in both centrifugated groups, one with a normal half-life of 27 + or - 1 S.E.M. d, and one with a significantly (p less than 0.01) shorter half-life of 15 + or - 2 S.E.M. d. An absolute polycythemia was also observed in both centrifuged groups. The results suggest that chronic centrifugation acts through some as-yet unknown mechanism to affect RBC population kinetics.

  20. Tangential Flow Ultrafiltration Allows Purification and Concentration of Lauric Acid-/Albumin-Coated Particles for Improved Magnetic Treatment

    PubMed Central

    Zaloga, Jan; Stapf, Marcus; Nowak, Johannes; Pöttler, Marina; Friedrich, Ralf P.; Tietze, Rainer; Lyer, Stefan; Lee, Geoffrey; Odenbach, Stefan; Hilger, Ingrid; Alexiou, Christoph

    2015-01-01

    Superparamagnetic iron oxide nanoparticles (SPIONs) are frequently used for drug targeting, hyperthermia and other biomedical purposes. Recently, we have reported the synthesis of lauric acid-/albumin-coated iron oxide nanoparticles SEONLA-BSA, which were synthesized using excess albumin. For optimization of magnetic treatment applications, SPION suspensions need to be purified of excess surfactant and concentrated. Conventional methods for the purification and concentration of such ferrofluids often involve high shear stress and low purification rates for macromolecules, like albumin. In this work, removal of albumin by low shear stress tangential ultrafiltration and its influence on SEONLA-BSA particles was studied. Hydrodynamic size, surface properties and, consequently, colloidal stability of the nanoparticles remained unchanged by filtration or concentration up to four-fold (v/v). Thereby, the saturation magnetization of the suspension can be increased from 446.5 A/m up to 1667.9 A/m. In vitro analysis revealed that cellular uptake of SEONLA-BSA changed only marginally. The specific absorption rate (SAR) was not greatly affected by concentration. In contrast, the maximum temperature Tmax in magnetic hyperthermia is greatly enhanced from 44.4 °C up to 64.9 °C by the concentration of the particles up to 16.9 mg/mL total iron. Taken together, tangential ultrafiltration is feasible for purifying and concentrating complex hybrid coated SPION suspensions without negatively influencing specific particle characteristics. This enhances their potential for magnetic treatment. PMID:26287178

  1. Tangential Flow Ultrafiltration Allows Purification and Concentration of Lauric Acid-/Albumin-Coated Particles for Improved Magnetic Treatment.

    PubMed

    Zaloga, Jan; Stapf, Marcus; Nowak, Johannes; Pöttler, Marina; Friedrich, Ralf P; Tietze, Rainer; Lyer, Stefan; Lee, Geoffrey; Odenbach, Stefan; Hilger, Ingrid; Alexiou, Christoph

    2015-01-01

    Superparamagnetic iron oxide nanoparticles (SPIONs) are frequently used for drug targeting, hyperthermia and other biomedical purposes. Recently, we have reported the synthesis of lauric acid-/albumin-coated iron oxide nanoparticles SEON(LA-BSA), which were synthesized using excess albumin. For optimization of magnetic treatment applications, SPION suspensions need to be purified of excess surfactant and concentrated. Conventional methods for the purification and concentration of such ferrofluids often involve high shear stress and low purification rates for macromolecules, like albumin. In this work, removal of albumin by low shear stress tangential ultrafiltration and its influence on SEON(LA-BSA) particles was studied. Hydrodynamic size, surface properties and, consequently, colloidal stability of the nanoparticles remained unchanged by filtration or concentration up to four-fold (v/v). Thereby, the saturation magnetization of the suspension can be increased from 446.5 A/m up to 1667.9 A/m. In vitro analysis revealed that cellular uptake of SEON(LA-BSA) changed only marginally. The specific absorption rate (SAR) was not greatly affected by concentration. In contrast, the maximum temperature Tmax in magnetic hyperthermia is greatly enhanced from 44.4 °C up to 64.9 °C by the concentration of the particles up to 16.9 mg/mL total iron. Taken together, tangential ultrafiltration is feasible for purifying and concentrating complex hybrid coated SPION suspensions without negatively influencing specific particle characteristics. This enhances their potential for magnetic treatment. PMID:26287178

  2. Thymoquinone, an active constituent of Nigella sativa seeds, binds with bilirubin and protects mice from hyperbilirubinemia and cyclophosphamide-induced hepatotoxicity.

    PubMed

    Laskar, Amaj A; Khan, Masood A; Rahmani, Arshad H; Fatima, Sana; Younus, Hina

    2016-08-01

    Some reports indicate that thymoquinone (TQ), the main constituent of Nigella sativa seeds, is hepatoprotective. The aim of this study was to determine whether TQ is able to bind directly to bilirubin, and whether TQ or liposomal formulation of TQ (Lip-TQ) can reduce cyclophosphamide (CYP)-induced liver toxicity, serum bilirubin level in mice. The binding of TQ with bilirubin was studied by UV-VIS, fluorescence and Near-UV CD spectroscopy. Inhibition of binding of bilirubin to erythrocytes by TQ was also examined. To increase the in vivo efficacy, Lip-TQ was prepared and used against CYP-induced toxicity. The protective role of TQ or Lip-TQ against CYP-induced toxicity was assessed by determining the liver function parameters, the levels of superoxide dismutase (SOD) and catalase (CAT), and histological studies. It was found that TQ binds to bilirubin and significantly inhibits the binding of bilirubin to erythrocytes. Lip-TQ (10 mg/kg) significantly reduced the levels of aspartate transaminase (AST) from 254 ± 48 to 66 ± 18 IU/L (P < 0.001), alanine transaminase (ALT) from 142 ± 28 to 47.8 ± 16 IU/L (P < 0.05) and serum bilirubin from 2.8 ± 0.50 to 1.24 ± 0.30 mg/dl (P < 0.05). Treatment with Lip-TQ reduced the CYP-induced inflammation and hemorrhage in liver tissues. Moreover, treatment with free or Lip-TQ protected the activity of SOD and CAT in CYP-injected mice. Therefore, TQ can reduce the level of bilirubin in systemic circulation in disease conditions that lead to hyperbilirubinemia and liver toxicity and hence may be used as a supplement in the treatment of liver ailments. PMID:27265787

  3. Bilirubin Oxidase from Myrothecium verrucaria Physically Absorbed on Graphite Electrodes. Insights into the Alternative Resting Form and the Sources of Activity Loss

    PubMed Central

    Tasca, Federico; Farias, Diego; Castro, Carmen; Acuna-Rougier, Cristina; Antiochia, Riccarda

    2015-01-01

    The oxygen reduction reaction is one of the most important chemical processes in energy converting systems and living organisms. Mediator-less, direct electro-catalytic reduction of oxygen to water was achieved on spectrographite electrodes modified by physical adsorption of bilirubin oxidases from Myrothecium verrucaria. The existence of an alternative resting form of the enzyme is validated. The effect on the catalytic cycle of temperature, pH and the presence of halogens in the buffer was investigated. Previous results on the electrochemistry of bilirubin oxidase and on the impact of the presence of halogens are reviewed and reinterpreted. PMID:26196288

  4. Prognostic significance of pretreatment albumin/globulin ratio in patients with hepatocellular carcinoma

    PubMed Central

    Deng, Yan; Pang, Qing; Miao, Run-Chen; Chen, Wei; Zhou, Yan-Yan; Bi, Jian-Bin; Liu, Su-Shun; Zhang, Jing-Yao; Qu, Kai; Liu, Chang

    2016-01-01

    Background Pretreatment nutritional and immunological statuses play an indispensable role in predicting the outcome of patients with various types of malignancies. The purpose of this study is to evaluate the predictive value of albumin/globulin ratio (AGR) in overall survival (OS) and recurrence in patients with hepatocellular carcinoma (HCC) following radical hepatic carcinectomy. Patients and methods This retrospective study included a total of 172 patients with HCC with complete medical and follow-up information between 2002 and 2012. AGR was calculated according to the following formula: AGR = albumin/globulin. Receiver operating characteristic curve analysis was performed to determine the optimal cutoff value. The associations of AGR with clinicopathological characteristics and prognosis were assessed. Further multivariate analysis using Cox regression model and subgroup analysis was performed to evaluate the predictive value. Results Receiver operating characteristic curve determined 37.65, 31.99, and 1.48 as the optimal cutoff values of albumin, globulin, and AGR in terms of 5-year OS or death, respectively. On the basis of the cutoff value of AGR, all the patients were divided, respectively, into low-AGR (n=105) and high-AGR (n=67) groups. AGR was found to be significantly correlated with age, cancer embolus, international normalized ratio, and postoperative outcome (P<0.05). Hepatitis B virus infection (hazard ratio [HR]: 2.125; 95% confidence interval [CI]: 1.285–3.153), tumor node metastasis stage (HR: 1.656; 95% CI: 1.234–2.223), serum albumin (HR: 0.546; 95% CI: 0.347–0.857), and AGR (HR: 0.402; 95% CI: 0.233–0.691) were independent predictors of OS via univariate and multivariate survival analyses. However, alpha-fetoprotein (HR: 1.708; 95% CI: 1.027–2.838), tumor node metastasis stage (HR: 1.464; 95% CI: 1.078–1.989), and AGR (HR: 0.493; 95% CI: 0.293–0.828) functioned as independent risk variables for predicting recurrence. Moreover

  5. Albumin Kinetics in Patients Undergoing Major Abdominal Surgery

    PubMed Central

    Norberg, Åke; Rooyackers, Olav; Segersvärd, Ralf; Wernerman, Jan

    2015-01-01

    Background The drop in plasma albumin concentration following surgical trauma is well known, but the temporal pattern of the detailed mechanisms behind are less well described. The aim of this explorative study was to assess changes in albumin synthesis and transcapillary escape rate (TER) following major surgical trauma, at the time of peak elevations in two well-recognized markers of inflammation. Methods This was a clinical trial of radiolabeled human serum albumin for the study of TER and plasma volume. Ten patients were studied immediately preoperatively and on the 2nd postoperative day after major pancreatic surgery. Albumin synthesis rate was measured by the flooding dose technique employing incorporation of isotopically labelled phenylalanine. Results Fractional synthesis rate of albumin increased from 11.7 (95% CI: 8.9, 14.5) to 15.0 (11.7, 18.4) %/day (p = 0.027), whereas the corresponding absolute synthesis rate was unchanged, 175 (138, 212) versus 150 (107, 192) mg/kg/day (p = 0.21). TER was unchanged, 4.9 (3.1, 6.8) %/hour versus 5.5 (3.9, 7.2) (p = 0.63). Plasma volume was unchanged but plasma albumin decreased from 33.5 (30.9, 36.2) to 22.1 (19.8, 24.3) g/L. (p<0.001). Conclusion Two days after major abdominal surgery, at the time-point when two biomarkers of generalised inflammation were at their peak and the plasma albumin concentration had decreased by 33%, we were unable to show any difference in the absolute synthesis rate of albumin, TER and plasma volume as compared with values obtained immediately pre-operatively. This suggests that capillary leakage, if elevated postoperatively, had ceased at that time-point. The temporal relations between albumin kinetics, capillary leakage and generalised inflammation need to be further explored. Trial Registration clinicaltrialsregister.eu: EudraCT 2010-08529-21 ClinicalTrials.gov NCT01194492 PMID:26313170

  6. Specific albumin binding to microvascular endothelium in culture

    SciTech Connect

    Schnitzer, J.E.; Carley, W.W.; Palade, G.E. )

    1988-03-01

    The specific binding of rat serum albumin (RSA) to confluent microvascular endothelial cells in culture derived from the vasculature of the rat epididymal fat pad was studied at 4{degree}C by radioassay and immunocytochemistry. Radioiodinated RSA ({sup 125}I-RSA) binding to the cells reached equilibrium at {approximately} 20 min incubation. Albumin binding was a slowly saturating function over concentrations ranging from 0.01 to 50 mg/ml. Specific RSA binding with a moderate apparent affinity constant of 1.0 mg/ml and with a maximum binding concentration of 90 ng/cm{sup 2} was immunolocalized with anti-RSA antibody to the outer (free) side of the enothelium. Scatchard analysis of the binding yielded a nonlinear binding curve with a concave-upward shape. Dissociation rate analysis supports negative cooperativity of albumin binding, but multiple binding sites may also be present. Albumin binding fulfilled many requirements for ligand specificity including saturability, reversibility, competibility, and dependence on both cell type and cell number. The results are discussed in terms of past in situ investigations on the localization of albumin binding to vascular endothelium and its effect on transendothelial molecular transport.

  7. Albumin-based nanocomposite spheres for advanced drug delivery systems.

    PubMed

    Misak, Heath E; Asmatulu, Ramazan; Gopu, Janani S; Man, Ka-Poh; Zacharias, Nora M; Wooley, Paul H; Yang, Shang-You

    2014-01-01

    A novel drug delivery system incorporating human serum albumin, poly(lactic-co-glycolic acid, magnetite nanoparticles, and therapeutic agent(s) was developed for potential application in the treatment of diseases such as rheumatoid arthritis and skin cancer. An oil-in-oil emulsion/solvent evaporation (O/OSE) method was modified to produce a drug delivery system with a diameter of 0.5–2 μm. The diameter was mainly controlled by adjusting the viscosity of albumin in the discontinuous phase of the O/OSE method. The drug-release study showed that the release of drug and albumin was mostly dependent on the albumin content of the drug delivery system, which is very similar to the drug occlusion-mesopore model. Cytotoxicity tests indicated that increasing the albumin content in the drug delivery system increased cell viability, possibly due to the improved biocompatibility of the system. Overall, these studies show that the proposed system could be a viable option as a drug delivery system in the treatment of many illnesses, such as rheumatoid arthritis, and skin and breast cancers. PMID:24106002

  8. Regional differences in pleural lymphatic albumin concentration in sheep

    SciTech Connect

    Albertine, K.H.; Schultz, E.L.; Wiener-Kronish, J.P.; Staub, N.C.

    1987-01-01

    We used quantitative reflectance autoradiography to compare the concentration of albumin in visceral pleural lymphatics at the cranial and caudal ends of the sheep's lung in the vertical (60 degrees head-up) and horizontal (supine) positions. Twelve to fourteen hours after injecting 125I-albumin intravenously we placed four anesthetized sheep in the vertical position to establish a microvascular hydrostatic pressure gradient along the vertical height of the lung. We placed two anesthetized sheep in the horizontal position. Four hours later, we fixed the left lung and removed visceral pleural tissue blocks from the cranial and caudal ends, separated by a 15-cm distance, along the costovertebral margin. We measured the silver grain density in the pleural lymphatic autoradiograms by dark-field reflectance microspectrophotometry. In the vertical position, the lymph albumin concentration at the cranial end (top) of the lung averaged 2.5 +/- 0.4 g/dl compared with the caudal end (bottom), which averaged 1.8 +/- 0.3 g/dl. The difference (42% greater at the top than the bottom) is significant (P less than 0.05). The computed gradient in perimicrovascular interstitial albumin osmotic pressure was 0.26 +/- 0.13 cmH2O/cm lung height. There were no differences between the cranial and caudal lymphatic groups in the two horizontal sheep. We conclude that in the sheep lung there is a gradient in perimicrovascular albumin concentration due to the vertical gradient in microvascular hydrostatic pressure.

  9. A Homogeneous Fluorescent Sensor for Human Serum Albumin

    PubMed Central

    Wang, Rongsheng E.; Tian, Ling; Chang, Yie-Hwa

    2012-01-01

    Human serum albumin is the most abundant protein in the body and is an important biomarker used for disease-related diagnosis. Although the traditional enzyme-linked immunosorbent assay (ELISA) approach can precisely measure the concentration of human serum albumin, the multi-step procedure and time-consuming preparations of ELISA limit its diagnostic applications, preventing accurate point-of-care testing, for example. Herein, we report the recent development of an antibody-based albumin sensor that allows for a homogeneous measurement of albumin concentrations in saliva, urine and serum, in which this type of sensor is validated for the first time. The assay only requires simple mixing, and relies on time-resolved (TR) fluorescence resonance energy transfer (FRET) to produce robust, sensitive signals. The whole process, from sample preparation to final read-out, is expected to take less than one hour and requires only a standard plate-reader, thus making the sensor a convenient and cost-effective tool for albumin analysis. PMID:22326845

  10. Biocompatibility of electrospun human albumin: a pilot study.

    PubMed

    Noszczyk, B H; Kowalczyk, T; Łyżniak, M; Zembrzycki, K; Mikułowski, G; Wysocki, J; Kawiak, J; Pojda, Z

    2015-01-01

    Albumin is rarely used for electrospinning because it does not form fibres in its native globular form. This paper presents a novel method for electrospinning human albumin from a solution containing pharmaceutical grade protein and 25% polyethylene oxide (PEO) used as the fibre-forming agent. After spontaneous cross-linking at body temperature, with no further chemicals added, the fibres become insoluble and the excess PEO can be washed out. Albumin deposited along the fibres retains its native characteristics, such as its non-adhesiveness to cells and its susceptibility for degradation by macrophages. To demonstrate this we evaluated the mechanical properties, biocompatibility and biodegradability of this novel product. After subcutaneous implantation in mice, albumin mats were completely resorbable within six days and elicited only a limited local inflammatory response. In vitro, the mats suppressed cell attachment and migration. As this product is inexpensive, produced from human pharmaceutical grade albumin without chemical modifications, retains its native protein properties and fulfils the specific requirements for anti-adhesive dressings, its clinical use can be expedited. We believe that it could specifically be used when treating paediatric patients with epidermolysis bullosa, in whom non-healing wounds occur after minor hand injuries which lead to rapid adhesions and devastating contractures. PMID:25727172

  11. Seeded growth of hydroxyapatite in the presence of dissolved albumin.

    PubMed

    Gilman, H; Hukins, D W

    1994-07-01

    Hydroxyapatite (HAP) crystals were grown from a supersaturated solution by the addition of a suspension of seed crystals at a controlled pH value of 7.4 and a temperature of 37 degrees C. The degree of supersaturation was comparable to that in biological fluids and was such that all HAP precipitated would be expected to deposit on the seeds. Albumin was added to some of the solutions to give a concentration in the range 75-250 micrograms cm-3. Samples of solution were removed at known times after the addition of seed crystals and their calcium ion concentrations were determined by atomic absorption spectroscopy. The decrease in the dissolved calcium concentration was taken to be a measure of crystal growth. In the absence of seeds, no decrease in calcium concentration occurred. The initial rate of HAP growth decreased linearly with albumin concentration, i.e., albumin was found to inhibit crystal growth. Inhibition kinetics were consistent with a Langmuir model in which a single albumin molecule was capable of binding to more than one growth site on the crystal surface. Comparison with published results indicated that albumin was a less potent inhibitor of HAP growth than phosphoproteins but was a more potent inhibitor than magnesium or citrate ions. PMID:8046435

  12. Albumin microvascular leakage in brains with diabetes mellitus.

    PubMed

    Fujihara, Ryuji; Chiba, Yoichi; Nakagawa, Toshitaka; Nishi, Nozomu; Murakami, Ryuta; Matsumoto, Koichi; Kawauchi, Machi; Yamamoto, Tetsuji; Ueno, Masaki

    2016-09-01

    Their aim was to examine whether microvascular leakage of endogenous albumin, a representative marker for blood-brain barrier (BBB) damage, was induced in the periventricular area of diabetic db/db mice because periventricular white matter hyperintensity formation in magnetic resonance images was accelerating in elderly patients with diabetes mellitus. Using light and electron microscopes, and semi-quantitative analysis techniques, immunoreactivity of endogenous albumin, indicating vascular permeability, was examined in the periventricular area and spinal cord of db/db mice and db/+m control mice. Greater immunoreactivity of albumin was observed in the vessel wall of the periventricular area of db/db mice than in controls. Additionally, weak immunoreactivity was observed in the spinal cord of both db/db mice and controls. The number of gold particles, indicating immunoreactivity of albumin, in the perivascular area of db/db mice was significantly higher than that of control mice, but there was no significant difference in the number of particles in the spinal cord between db/db mice and controls. These findings suggest that albumin microvascular leakage, or BBB breakdown, is induced in the periventricular area of diabetic mice. Microsc. Res. Tech. 79:833-837, 2016. © 2016 Wiley Periodicals, Inc. PMID:27333535

  13. Glycated albumin is an optimal biomarker for gestational diabetes mellitus

    PubMed Central

    HUANG, YAPING; HU, YONGWEI; MA, YU; YE, GUANGYONG

    2015-01-01

    Gestational diabetes mellitus (GDM) refers to abnormal glucose tolerance, which is a common complication that occurs in some women for the first time during the gestation period. However, the relationship between onset of GDM and factors including advanced age and a family history of diabetes remains to be determined. The study aimed to examine the clinical significance of the detection of glycated albumin (GA) in pregnant women with GDM. A total of 893 cases of pregnant women with GDM were included, with 661 healthy pregnant women serving as the normal controls. A conditional logistic regression model was used to analyze the univariate and multivariate data to estimate the odds ratio (OR) and 95% confidence interval (95% CI). As the gestational weeks increased, the fasting blood glucose (FGP) concentration and GA-L value of the pregnant women in the normal control group gradually decreased whereas those of pregnant women with GDM greatly increased. The univariate analysis revealed that the impact factors on the occurrence of early-onset neonatal sepsis included, mother's age >35 years, complication of pregnancy hypertension, family history of hypertension, family history of diabetes, cesarean delivery, height, BMI, GA-L, and FGP. The multivariate logistic regression analysis revealed that the complication of pregnancy hypertension (OR=3.302; 95% CI, 1.705–6.394), family history of hypertension (OR=2.970; 95% CI, 1.520–5.801), GA-L (OR=1.556; 95% CI, 0.940–2.012) and FGP (OR=5.431; 95% CI, 4.097–7.198) were the main factors for pregnant women with GDM. In conclusion, pregnant women with GDM may be affected by various factors. Additionally, GA may be applied to reflect the recent blood glucose control on pregnant women with GDM. PMID:26668607

  14. Metastable and equilibrium phase diagrams of unconjugated bilirubin IXα as functions of pH in model bile systems: Implications for pigment gallstone formation

    PubMed Central

    Berman, Marvin D.

    2014-01-01

    Metastable and equilibrium phase diagrams for unconjugated bilirubin IXα (UCB) in bile are yet to be determined for understanding the physical chemistry of pigment gallstone formation. Also, UCB is a molecule of considerable biomedical importance because it is a potent antioxidant and an inhibitor of atherogenesis. We employed principally a titrimetric approach to obtain metastable and equilibrium UCB solubilities in model bile systems composed of taurine-conjugated bile salts, egg yolk lecithin (mixed long-chain phosphatidylcholines), and cholesterol as functions of total lipid concentration, biliary pH values, and CaCl2 plus NaCl concentrations. Metastable and equilibrium precipitation pH values were obtained, and average pKa values of the two carboxyl groups of UCB were calculated. Added lecithin and increased temperature decreased UCB solubility markedly, whereas increases in bile salt concentrations and molar levels of urea augmented solubility. A wide range of NaCl and cholesterol concentrations resulted in no specific effects, whereas added CaCl2 produced large decreases in UCB solubilities at alkaline pH values only. UV-visible absorption spectra were consistent with both hydrophobic and hydrophilic interactions between UCB and bile salts that were strongly influenced by pH. Reliable literature values for UCB compositions of native gallbladder biles revealed that biles from hemolytic mice and humans with black pigment gallstones are markedly supersaturated with UCB and exhibit more acidic pH values, whereas biles from nonstone control animals and patients with cholesterol gallstone are unsaturated with UCB. PMID:25359538

  15. Metastable and equilibrium phase diagrams of unconjugated bilirubin IXα as functions of pH in model bile systems: Implications for pigment gallstone formation.

    PubMed

    Berman, Marvin D; Carey, Martin C

    2015-01-01

    Metastable and equilibrium phase diagrams for unconjugated bilirubin IXα (UCB) in bile are yet to be determined for understanding the physical chemistry of pigment gallstone formation. Also, UCB is a molecule of considerable biomedical importance because it is a potent antioxidant and an inhibitor of atherogenesis. We employed principally a titrimetric approach to obtain metastable and equilibrium UCB solubilities in model bile systems composed of taurine-conjugated bile salts, egg yolk lecithin (mixed long-chain phosphatidylcholines), and cholesterol as functions of total lipid concentration, biliary pH values, and CaCl2 plus NaCl concentrations. Metastable and equilibrium precipitation pH values were obtained, and average pKa values of the two carboxyl groups of UCB were calculated. Added lecithin and increased temperature decreased UCB solubility markedly, whereas increases in bile salt concentrations and molar levels of urea augmented solubility. A wide range of NaCl and cholesterol concentrations resulted in no specific effects, whereas added CaCl2 produced large decreases in UCB solubilities at alkaline pH values only. UV-visible absorption spectra were consistent with both hydrophobic and hydrophilic interactions between UCB and bile salts that were strongly influenced by pH. Reliable literature values for UCB compositions of native gallbladder biles revealed that biles from hemolytic mice and humans with black pigment gallstones are markedly supersaturated with UCB and exhibit more acidic pH values, whereas biles from nonstone control animals and patients with cholesterol gallstone are unsaturated with UCB. PMID:25359538

  16. Scaffold materials from glycosylated and PEGylated bovine serum albumin.

    PubMed

    Wang, Kai; David, Allan E; Choi, Young-Suk; Wu, Yonnie; Buschle-Diller, Gisela

    2015-09-01

    Bovine serum albumin has been PEGylated and glycosylated to create mimetic materials for the extracellular matrix (ECM) with potential tissue engineering applications. Different surfaces for cell adhesion were achieved by crosslinking the initial albumin product and forming either a coating or a sponge-like three-dimensional morphology to mimic the mesh structure of natural ECM. The biocompatibility of the albumin matrix with mammalian cells was evaluated using cell culture assays with NIH 3T3 cells. The results indicated that glycoprotein composition and specific morphology of the assembly can improve the cell growth environment. These ECM mimetic structures might eventually be considered to serve as alternatives for the more expensive collagen and elastin based ECM substances currently in use in tissue engineering. PMID:25691091

  17. 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

  18. Unraveling the Interaction between FcRn and Albumin: Opportunities for Design of Albumin-Based Therapeutics

    PubMed Central

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

    2015-01-01

    The neonatal Fc receptor (FcRn) was first found to be responsible for transporting antibodies of the immunoglobulin G (IgG) class from the mother to the fetus or neonate as well as for protecting IgG from intracellular catabolism. However, it has now become apparent that the same receptor also binds albumin and plays a fundamental role in homeostatic regulation of both IgG and albumin, as FcRn is expressed in many different cell types and organs at diverse body sites. Thus, to gain a complete understanding of the biological function of each ligand, and also their distribution in the body, an in-depth characterization of how FcRn binds and regulates the transport of both ligands is necessary. Importantly, such knowledge is also relevant when developing new drugs, as IgG and albumin are increasingly utilized in therapy. This review discusses our current structural and biological understanding of the relationship between FcRn and its ligands, with a particular focus on albumin and design of albumin-based therapeutics. PMID:25674083

  19. PEGylated Albumin-Based Polyion Complex Micelles for Protein Delivery.

    PubMed

    Jiang, Yanyan; Lu, Hongxu; Chen, Fan; Callari, Manuela; Pourgholami, Mohammad; Morris, David L; Stenzel, Martina H

    2016-03-14

    An increasing amount of therapeutic agents are based on proteins. However, proteins as drug have intrinsic problems such as their low hydrolytic stability. Delivery of proteins using nanoparticles has increasingly been the focus of interest with polyion complex micelles, prepared from charged block copolymer and the oppositely charged protein, as an example of an attractive carrier for proteins. Inspired by this approach, a more biocompatible pathway has been developed here, which replaces the charged synthetic polymer with an abundant protein, such as albumin. Although bovine serum albumin (BSA) was observed to form complexes with positively charged proteins directly, the resulting protein nanoparticle were not stable and aggregated to large precipitates over the course of a day. Therefore, maleimide functionalized poly(oligo (ethylene glycol) methyl ether methacrylate) (MI-POEGMEMA) (Mn = 26000 g/mol) was synthesized to generate a polymer-albumin conjugate, which was able to condense positively charged proteins, here lysozyme (Lyz) as a model. The PEGylated albumin polyion complex micelle with lysozyme led to nanoparticles between 15 and 25 nm in size depending on the BSA to Lyz ratio. The activity of the encapsulated protein was tested using Sprouty 1 (C-12; Spry1) proteins, which can act as an endogenous angiogenesis inhibitor. Condensation of Spry1 with the PEGylated albumin could improve the anticancer efficacy of Spry1 against the breast cancer cells lowering the IC50 value of the protein. Furthermore, the high anticancer efficacy of the POEGMEMA-BSA/Spry1 complex micelle was verified by effectively inhibiting the growth of three-dimensional MCF-7 multicellular tumor spheroids. The PEGylated albumin complex micelle has great potential as a drug delivery vehicle for a new generation of cancer pharmaceuticals. PMID:26809948

  20. Statin-sensitive endocytosis of albumin by glomerular podocytes.

    PubMed

    Eyre, Jeanette; Ioannou, Kyriakos; Grubb, Blair D; Saleem, Moin A; Mathieson, Peter W; Brunskill, Nigel J; Christensen, Erik I; Topham, Peter S

    2007-02-01

    Glomerular podocytes are critical regulators of glomerular permeability via the slit diaphragm and may play a role in cleaning the glomerular filter. Whether podocytes are able to endocytose proteins is uncertain. We studied protein endocytosis in conditionally immortalized mouse and human podocytes using FITC-albumin by direct quantitative assay and by fluorescence microscopy and electron microscopy in mouse podocytes. Furthermore, in vivo uptake was studied in human, rat, and mouse podocytes. Both mouse and human podocytes displayed specific one-site binding for FITC-albumin with K(d) of 0.91 or 0.44 mg/ml and B(max) of 3.15 or 0.81 microg/mg cell protein, respectively. In addition, they showed avid endocytosis of FITC-albumin with K(m) of 9.48 or 4.5 mg/ml and V(max) of 474.3 or 97.4 microg.mg cell protein(-1).h(-1), respectively. Immunoglobulin and transferrin were inefficient competitors of this process, indicating some specificity for albumin. Accumulation of endocytosed albumin could be demonstrated in intracellular vesicles by fluorescence confocal microscopy and electron microscopy. Endocytosis was sensitive to pretreatment with simvastatin. In vivo accumulation of albumin was found in all three species but was most pronounced in the rat. We conclude that podocytes are able to endocytose protein in a statin-sensitive manner. This function is likely to be highly significant in health and disease. In addition, protein endocytosis by podocytes may represent a useful, measurable phenotypic characteristic against which potentially injurious or beneficial interventions can be assessed. PMID:17032937

  1. Polymer resins with amino acid containing pendants for sorption of bilirubin. II. Polyamide resins with various basic amino acids.

    PubMed

    Henning, D S; Brown, G R; St-Pierre, L E

    1986-01-01

    Short peptides, three to eight amino acids in length, containing various combinations of alanine, arginine, lysine, histidine and tyrosine have been synthesized onto water-swellable polyamide resin by the solid phase peptide synthesis method. The amount of bilirubin adsorbed from aqueous buffer solution (pH = 7.8) by the resins increases with increasing basicity of the amino acids in the pendant. As the number of basic amino acids on the pendant is increased from one to five a 4.7 fold enhancement in the adsorption capacity is seen for arginine while a 9.3 fold enhancement is obtained for lysine. A corresponding increase in length for the non-basic histidine results in a 6 fold enhancement. With alanine the adsorption capacity is uneffected by an increase in pendant length. PMID:3957453

  2. Increasing the catalytic activity of Bilirubin oxidase from Bacillus pumilus: Importance of host strain and chaperones proteins.

    PubMed

    Gounel, Sébastien; Rouhana, Jad; Stines-Chaumeil, Claire; Cadet, Marine; Mano, Nicolas

    2016-07-20

    Aggregation of recombinant proteins into inclusion bodies (IBs) is the main problem of the expression of multicopper oxidase in Escherichia coli. It is usually attributed to inefficient folding of proteins due to the lack of copper and/or unavailability of chaperone proteins. The general strategies reported to overcome this issue have been focused on increasing the intracellular copper concentration. Here we report a complementary method to optimize the expression in E. coli of a promising Bilirubin oxidase (BOD) isolated from Bacillus pumilus. First, as this BOD has a disulfide bridge, we switched E.coli strain from BL21 (DE3) to Origami B (DE3), known to promote the formation of disulfide bridges in the bacterial cytoplasm. In a second step, we investigate the effect of co-expression of chaperone proteins on the protein production and specific activity. Our strategy allowed increasing the final amount of enzyme by 858% and its catalytic rate constant by 83%. PMID:27165502

  3. Neuronal uptake of serum albumin is associated with neuron damage during the development of epilepsy

    PubMed Central

    Liu, Zanhua; Liu, Jinjie; Wang, Suping; Liu, Sibo; Zhao, Yongbo

    2016-01-01

    It is well established that brain blood barrier dysfunction following the onset of seizures may lead to serum albumin extravasation into the brain. However, the effect of albumin extravasation on the development of epilepsy is yet to be fully elucidated. Previous studies have predominantly focused on the effect of albumin absorption by astrocytes; however, the present study investigated the effects of neuronal uptake of albumin in vitro and in kainic acid-induced Sprague-Dawley rat models of temporal lobe epilepsy. In the present study, electroencephalogram recordings were conducted to record seizure onset, Nissl and Evans blue staining were used to detect neuronal damage and albumin extravasation, respectively, and double immunofluorescence was used to explore neuronal absorption of albumin. Cell counting was also conducted in vitro to determine whether albumin contributes to neuronal death. The results of the present study indicated that extravasated serum albumin was absorbed by neurons, and the neurons that had absorbed albumin died and were dissolved 28 days after seizure onset in vivo. Furthermore, significant neuronal death was detected after albumin absorption in vitro in a dose- and time-dependent manner. These results suggested that albumin may be absorbed by neurons following the onset of seizures. Furthermore, the results indicated that neuronal albumin uptake may be associated with neuronal damage and death in epileptic seizures. Therefore, attenuating albumin extravasation following epileptic seizures may reduce brain damage and slow the development of epilepsy. PMID:27446263

  4. Mechanism of increased clearance of glycated albumin by proximal tubule cells.

    PubMed

    Wagner, Mark C; Myslinski, Jered; Pratap, Shiv; Flores, Brittany; Rhodes, George; Campos-Bilderback, Silvia B; Sandoval, Ruben M; Kumar, Sudhanshu; Patel, Monika; Ashish; Molitoris, Bruce A

    2016-05-01

    Serum albumin is the most abundant plasma protein and has a long half-life due to neonatal Fc receptor (FcRn)-mediated transcytosis by many cell types, including proximal tubule cells of the kidney. Albumin also interacts with, and is modified by, many small and large molecules. Therefore, the focus of the present study was to address the impact of specific known biological albumin modifications on albumin-FcRn binding and cellular handling. Binding at pH 6.0 and 7.4 was performed since FcRn binds albumin strongly at acidic pH and releases it after transcytosis at physiological pH. Equilibrium dissociation constants were measured using microscale thermophoresis. Since studies have shown that glycated albumin is excreted in the urine at a higher rate than unmodified albumin, we studied glucose and methylgloxal modified albumins (21 days). All had reduced affinity to FcRn at pH 6.0, suggesting these albumins would not be returned to the circulation via the transcytotic pathway. To address why modified albumin has reduced affinity, we analyzed the structure of the modified albumins using small-angle X-ray scattering. This analysis showed significant structural changes occurring to albumin with glycation, particularly in the FcRn-binding region, which could explain the reduced affinity to FcRn. These results offer an explanation for enhanced proximal tubule-mediated sorting and clearance of abnormal albumins. PMID:26887834

  5. Acute hypoproteinemic fluid overload: its determinants, distribution, and treatment with concentrated albumin and diuretics.

    PubMed

    Pappova, E; Bachmeier, W; Crevoisier, J L; Kollar, J; Kollar, M; Tobler, P; Zahler, H W; Zaugg, D; Lundsgaard-Hansen, P

    1977-01-01

    We simulated the use of massive volumes of crystalloid fluids as a treatment of acute plasma loss in a standardized experimental model and studied the factors determining the retention or excretion of the resulting acute hypoproteinemic fluid overload, its distribution within the body, and its treatment with concentrated albumin and diuretics. In accordance with the classic Starling concept, the serum protein level, i.e. the serum colloid osmotic pressure, determined the excretion/retention ratio of a given water and sodium load. Of the total fluid retention, fat and muscle each accommodated 25%, whereas the skin, which contributes only 7% to the total body weight, accounted for 37% and increased its volume by roughly one third. Concentrated albumin promoted fluid excretion in direct proportion to the achieved increment of the serum protein level and abolished the edema of fat, muscle and skin. Furosemide was virtually ineffective. The implications of these results for the 'adult respiratory distress syndrome' and disturbed wound healing are discussed and related to the concept of a critical threshold of the serum protein level. PMID:919420

  6. Ischemia-Modified Albumin: Could It Be a New Oxidative Stress Biomarker for Colorectal Carcinoma?

    PubMed Central

    Bulbuller, Nurullah; Eren, Esin; Abusoglu, Sedat; Akgol, Evren; Cetiner, Mustafa; Yılmaz, Necat

    2013-01-01

    Background/Aims An impaired oxidative/antioxidative status plays an important role in the pathogenesis of many diseases, including cancer. The aim of this study was to evaluate the levels of the novel marker ischemia-modified albumin (IMA) and albumin-adjusted IMA (Adj-IMA) in patients with colorectal cancer (CRC) and look for the associations of these with the total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI). Methods Forty patients with CRC (19 females and 21 males; mean age, 56.5±2.1 years) and 39 age- and sex-matched healthy people (22 females and 17 males; mean age, 56.0±1.7 years) were included in this study. Serum levels of IMA, TAS, and TOS were analyzed, and the OSI was calculated. Results Serum IMA, TOS, and OSI levels were significantly higher in patients with CRC than in controls (p<0.0001), whereas TAS levels were significantly lower in CRC patients (p=0.03). There was no significant difference in serum Adj-IMA levels between groups (p=0.32). Conclusions In this study, the oxidative/antioxidant status was impaired in favor of oxidative stress in CRC patients. This observation was not confirmed by IMA measurement. Further studies are needed to establish the relationship between IMA and oxidative stress parameters in CRC and other cancers. PMID:24312708

  7. Endogenously elevated bilirubin modulates kidney function and protects from circulating oxidative stress in a rat model of adenine-induced kidney failure

    PubMed Central

    Boon, Ai-Ching; Lam, Alfred K.; Gopalan, Vinod; Benzie, Iris F.; Briskey, David; Coombes, Jeff S.; Fassett, Robert G.; Bulmer, Andrew C.

    2015-01-01

    Mildly elevated bilirubin is associated with a reduction in the presence and progression of chronic kidney disease and related mortality, which may be attributed to bilirubin’s antioxidant properties. This study investigated whether endogenously elevated bilirubin would protect against adenine-induced kidney damage in male hyperbilirubinaemic Gunn rats and littermate controls. Animals were orally administered adenine or methylcellulose solvent (vehicle) daily for 10 days and were then monitored for 28 days. Serum and urine were assessed throughout the protocol for parameters of kidney function and antioxidant/oxidative stress status and kidneys were harvested for histological examination upon completion of the study. Adenine-treated animals experienced weight-loss, polyuria and polydipsia; however, these effects were significantly attenuated in adenine-treated Gunn rats. No difference in the presence of dihydroadenine crystals, lymphocytic infiltration and fibrosis were noted in Gunn rat kidneys versus controls. However, plasma protein carbonyl and F2-isoprostane concentrations were significantly decreased in Gunn rats versus controls, with no change in urinary 8-oxo-7,8-dihydro-2′-deoxyguanosine or kidney tissue F2-isoprostane concentrations. These data indicated that endogenously elevated bilirubin specifically protects from systemic oxidative stress in the vascular compartment. These data may help to clarify the protective relationship between bilirubin, kidney function and cardiovascular mortality in clinical investigations. PMID:26498893

  8. Crigler-Najjar syndrome

    MedlinePlus

    ... biopsy Total bilirubin level Unconjugated (unbound) bilirubin in blood ... this is done using bilirubin lights (bili or 'blue' lights). ... Blood transfusions may help control the amount of bilirubin ...

  9. Developmental onset of bilirubin-induced neurotoxicity involves Toll-like receptor 2-dependent signaling in humanized UDP-glucuronosyltransferase1 mice.

    PubMed

    Yueh, Mei-Fei; Chen, Shujuan; Nguyen, Nghia; Tukey, Robert H

    2014-02-21

    Biological and signaling events that connect developmentally induced hyperbilirubinemia to bilirubin-induced neurological dysfunction (BIND) and CNS toxicity in humans are poorly understood. In mammals, UDP-glucuronosyltransferase 1A1 (UGT1A1) is the sole enzyme responsible for bilirubin glucuronidation, a rate-limiting step necessary for bilirubin metabolism and clearance. Humanized mice that express the entire UGT1 locus (hUGT1) and the UGT1A1 gene, develop neonatal hyperbilirubinemia, with 8-10% of hUGT1 mice succumbing to CNS damage, a phenotype that is presented by uncontrollable seizures. We demonstrate that neuroinflammation and reactive gliosis are prominent features of bilirubin brain toxicity, and a disturbed redox status resulting from activation of NADPH oxidase is an important contributing mechanism found in BIND. Using knock-out mice and primary brain cells, we connect a key pattern recognition receptor, Toll-like receptor 2 (TLR2), to hyperbilirubinemia-induced signaling. We illustrate a requirement for TLR2 signaling in regulating gliosis, proinflammatory mediators, and oxidative stress when neonatal mice encounter severe hyperbilirubinemia. TLR2-mediated gliosis strongly correlates with pronounced neuroinflammation in the CNS with up-regulation of TNFα, IL-1β, and IL-6, creating a pro-inflammatory CNS environment. Gene expression and immunohistochemistry staining show that hUGT1/Tlr2(-/-) mice fail to activate glial cells, proinflammatory cytokines, and stress response genes. In addition, bilirubin-induced apoptosis was significantly enhanced by blocking TLR2 signaling indicating its anti-apoptotic property. Consequently, a higher neonatal death rate (57.1%) in hUGT1/Tlr2(-/-) mice was observed when compared with hUGT1 mice (8.7%). These results suggest that TLR2 signaling and microglia neuroinflammation are linked to a repair and/or protection mode against BIND. PMID:24403077

  10. Effect of baseline serum albumin concentration on outcome of resuscitation with albumin or saline in patients in intensive care units: analysis of data from the saline versus albumin fluid evaluation (SAFE) study

    PubMed Central

    Study Investigators, SAFE

    2006-01-01

    Objective To determine whether outcomes of resuscitation with albumin or saline in the intensive care unit depend on patients' baseline serum albumin concentration. Design Analysis of data from a double blind, randomised controlled trial. Setting Intensive care units of 16 hospitals in Australia and New Zealand. Participants 6045 participants in the saline versus albumin fluid evaluation (SAFE) study. Interventions Fluid resuscitation with 4% albumin or saline in patients with a baseline serum albumin concentration of 25 g/l or less or more than 25 g/l. Main outcome measures Primary outcome was all cause mortality at 28 days. Secondary outcomes were length of stay in the intensive care unit, length of stay in hospital, duration of renal replacement therapy, and duration of mechanical ventilation. Main results The odds ratios for death for albumin compared with saline for patients with a baseline serum albumin concentration of 25 g/l or less and more than 25 g/l were 0.87 and 1.09, respectively (ratio of odds ratios 0.80, 95% confidence interval 0.63 to 1.02); P=0.08 for heterogeneity. No significant interaction was found between baseline serum albumin concentration as a continuous variable and the effect of albumin and saline on mortality. No consistent interaction was found between baseline serum albumin concentration and treatment effects on length of stay in the intensive care unit, length of hospital stay, duration of renal replacement therapy, or duration of mechanical ventilation. Conclusion The outcomes of resuscitation with albumin and saline are similar irrespective of patients' baseline serum albumin concentration. Trial registration ISRCTN76588266. PMID:17040925

  11. Use of perioperative hydroxyethyl starch 6% and albumin 5% in elective joint arthroplasty and association with adverse outcomes: a retrospective population based analysis

    PubMed Central

    Opperer, Mathias; Poeran, Jashvant; Rasul, Rehana; Mazumdar, Madhu

    2015-01-01

    Objective To determine whether the perioperative use of hydroxyethyl starch 6% and albumin 5% in elective joint arthroplasties are associated with an increased risk for perioperative complications. Design Retrospective cohort study of population based data between 2006 and 2013. Setting Data from 510 different hospitals across the United States participating in the Premier Perspective database. Participants 1 051 441 patients undergoing elective total hip and knee arthroplasties. Exposures Perioperative fluid resuscitation with hydroxyethyl starch 6% or albumin 5%, or neither. Main outcome measures Acute renal failure and thromboembolic, cardiac, and pulmonary complications. Results Compared with patients who received neither colloid, perioperative fluid resuscitation with hydroxyethyl starch 6% or albumin 5% was associated with an increased risk of acute renal failure (odds ratios 1.23 (95% confidence interval 1.13 to 1.34) and 1.56 (1.36 to 1.78), respectively) and most other complications. A recent decrease in hydroxyethyl starch 6% use was noted, whereas that of albumin 5% increased. Conclusions Similar to studies in critically ill patients, we showed that use of hydroxyethyl starch 6% was associated with an increased risk of acute renal failure and other complications in the elective perioperative orthopedic setting. This increased risk also applied to albumin 5%. These findings raise questions regarding the widespread use of these colloids in elective joint arthroplasty procedures. PMID:25817299

  12. Liver Support With Albumin Dialysis Reduces Hepatitis C Virus Viremia and Facilitates Antiviral Treatment of Severe Hepatitis C Virus Recurrence After Liver Transplantation.

    PubMed

    Ibáñez-Samaniego, Luis; Catalina, María-Vega; Rincón, Diego; Lo Iacono, Oreste; Fernández, Ainhoa; Clemente, Gerardo; Bañares, Rafael; Vaquero, Javier; Salcedo, Magdalena

    2016-04-01

    Patients with severe hepatitis C virus (HCV) recurrence after liver transplantation (LT) present an ominous prognosis, rarely achieving sustained virological response (SVR). Dialysis procedures may transiently decrease the HCV viral load, but the effect of albumin dialysis is currently unknown. Here, we evaluated the impact of albumin dialysis using the Molecular Adsorbent Recirculating System (MARS) used as a co-adjuvant antiviral treatment for severe HCV recurrence after LT. Thirteen patients (11 males, median age 48 years) with fibrosing cholestatic hepatitis or METAVIR fibrosis score ≥ F3 with severe portal hypertension underwent three consecutive MARS sessions. Antiviral therapy was initiated in 11 patients within 24 h after the MARS sessions. A contemporary cohort of seven patients who did not follow the MARS protocol is shown for comparison. MARS treatment resulted in consistent decreases of viral load from 7.59 log10 IU/mL [6.15-8.90] to 6.79 log10 IU/mL [5.18-7.84] (P = 0.003) as well as in decreases of serum bilirubin, gamma-glutamyl transpeptidase, alanine aminotransferase and aspartate aminotransferase (all P < 0.05). The overall rate of SVR was 0% in the Control group and 54.6% in patients initiating antiviral therapy within 24 h after MARS. Survival at 1 and 3 years was, respectively, 93% and 70% in patients undergoing MARS, compared with 29% and 14% in the Control group (P = 0.001). No major adverse events related to MARS treatment were observed. In conclusion, the use of MARS may facilitate the achievement of SVR and improve the prognosis of patients with severe HCV-recurrence after LT by reducing viral load and improving liver function prior to antiviral therapy. PMID:26929255

  13. Human serum albumin homeostasis: a new look at the roles of synthesis, catabolism, renal and gastrointestinal excretion, and the clinical value of serum albumin measurements.

    PubMed

    Levitt, David G; Levitt, Michael D

    2016-01-01

    Serum albumin concentration (CP) is a remarkably strong prognostic indicator of morbidity and mortality in both sick and seemingly healthy subjects. Surprisingly, the specifics of the pathophysiology underlying the relationship between CP and ill-health are poorly understood. This review provides a summary that is not previously available in the literature, concerning how synthesis, catabolism, and renal and gastrointestinal clearance of albumin interact to bring about albumin homeostasis, with a focus on the clinical factors that influence this homeostasis. In normal humans, the albumin turnover time of about 25 days reflects a liver albumin synthesis rate of about 10.5 g/day balanced by renal (≈6%), gastrointestinal (≈10%), and catabolic (≈84%) clearances. The acute development of hypoalbuminemia with sepsis or trauma results from increased albumin capillary permeability leading to redistribution of albumin from the vascular to interstitial space. The best understood mechanism of chronic hypoalbuminemia is the decreased albumin synthesis observed in liver disease. Decreased albumin production also accounts for hypoalbuminemia observed with a low-protein and normal caloric diet. However, a calorie- and protein-deficient diet does not reduce albumin synthesis and is not associated with hypoalbuminemia, and CP is not a useful marker of malnutrition. In most disease states other than liver disease, albumin synthesis is normal or increased, and hypoalbuminemia reflects an enhanced rate of albumin turnover resulting either from an increased rate of catabolism (a poorly understood phenomenon) or enhanced loss of albumin into the urine (nephrosis) or intestine (protein-losing enteropathy). The latter may occur with subtle intestinal pathology and hence may be more prevalent than commonly appreciated. Clinically, reduced CP appears to be a result rather than a cause of ill-health, and therapy designed to increase CP has limited benefit. The ubiquitous occurrence of

  14. Human serum albumin homeostasis: a new look at the roles of synthesis, catabolism, renal and gastrointestinal excretion, and the clinical value of serum albumin measurements

    PubMed Central

    Levitt, David G; Levitt, Michael D

    2016-01-01

    Serum albumin concentration (CP) is a remarkably strong prognostic indicator of morbidity and mortality in both sick and seemingly healthy subjects. Surprisingly, the specifics of the pathophysiology underlying the relationship between CP and ill-health are poorly understood. This review provides a summary that is not previously available in the literature, concerning how synthesis, catabolism, and renal and gastrointestinal clearance of albumin interact to bring about albumin homeostasis, with a focus on the clinical factors that influence this homeostasis. In normal humans, the albumin turnover time of about 25 days reflects a liver albumin synthesis rate of about 10.5 g/day balanced by renal (≈6%), gastrointestinal (≈10%), and catabolic (≈84%) clearances. The acute development of hypoalbuminemia with sepsis or trauma results from increased albumin capillary permeability leading to redistribution of albumin from the vascular to interstitial space. The best understood mechanism of chronic hypoalbuminemia is the decreased albumin synthesis observed in liver disease. Decreased albumin production also accounts for hypoalbuminemia observed with a low-protein and normal caloric diet. However, a calorie- and protein-deficient diet does not reduce albumin synthesis and is not associated with hypoalbuminemia, and CP is not a useful marker of malnutrition. In most disease states other than liver disease, albumin synthesis is normal or increased, and hypoalbuminemia reflects an enhanced rate of albumin turnover resulting either from an increased rate of catabolism (a poorly understood phenomenon) or enhanced loss of albumin into the urine (nephrosis) or intestine (protein-losing enteropathy). The latter may occur with subtle intestinal pathology and hence may be more prevalent than commonly appreciated. Clinically, reduced CP appears to be a result rather than a cause of ill-health, and therapy designed to increase CP has limited benefit. The ubiquitous occurrence of

  15. Effect of Human and Bovine Serum Albumin on kinetic Chemiluminescence of Mn (III)-Tetrakis (4-Sulfonatophenyl) Porphyrin-Luminol-Hydrogen Peroxide System

    PubMed Central

    Kazemi, Sayed Yahya; Abedirad, Seyed Mohammad

    2012-01-01

    The present work deals with an attempt to study the effect of human and bovine serum albumin on kinetic parameters of chemiluminescence of luminol-hydrogen peroxide system catalyzed by manganese tetrasulfonatophenyl porphyrin (MnTSPP). The investigated parameters involved pseudo-first-order rise and fall rate constant for the chemiluminescence burst, maximum level intensity, time to reach maximum intensity, total light yield, and values of the intensity at maximum CL which were evaluated by nonlinear least square program KINFIT. Because of interaction of metalloporphyrin with proteins, the CL parameters are drastically affected. The systems resulted in Stern-Volmer plots with kQ values of 3.17 × 105 and 3.7 × 105 M−1 in the quencher concentration range of 1.5 × 10−6 to 1.5 × 10−5 M for human serum albumin (HSA) and bovine serum albumin (BSA), respectively. PMID:22645466

  16. Prognostic Significance of Preoperative Albumin-Globulin Ratio in Patients with Upper Tract Urothelial Carcinoma

    PubMed Central

    Zhou, Li-Qun; He, Zhi-Song; Shen, Cheng; He, Qun; Li, Jun; Liu, Li-Bo; Wang, Cong; Chen, Xiao-Yu; Fan, Yu; Hu, Shuai; Zhang, Lei; Han, Wen-Ke; Jin, Jie

    2015-01-01

    Background Preoperative albumin-globulin ratio (AGR) reflects both malnutrition and systemic inflammation in cancer patients. In particular, systemic inflammation has been reported to contribute to tumor progression and poor oncological outcome in various malignancies. However, the prognostic value of preoperative AGR in upper tract urothelial carcinoma (UTUC) has not been examined. Methods We retrospectively reviewed medical data of 187 operable UTUC patients in a Chinese cohort with a high incidence of chronic kidney disease (CKD). AGR was calculated as [AGR = albumin/(serum total protein—albumin)]. The associations of preoperative AGR with clinicopathologic characteristics and prognosis were assessed. Multivariate analyses using Cox regression models were performed to determine the independent prognostic factors. Results The median (IQR) preoperative AGR was 1.50 (1.30–1.70), and the optimal cutoff value was determined to be 1.45 according to the receiver operating curve analysis. Low AGR was significantly associated with female gender, high CKD stage and tumor grade (P < 0.05). Eighty-three patients died before the follow-up endpoint. Kaplan-Meier analysis showed that an AGR < 1.45 predicted significantly poorer overall and cancer-specific survivals compared to an AGR ≥ 1.45 (P < 0.001 and P = 0.008, respectively). Multivariate analyses showed that an AGR < 1.45 was an independent risk factor for poorer overall and cancer-specific survivals (P = 0.002 and P = 0.015, respectively). Conclusions Preoperative AGR can act as an effective biomarker with easy accessibility for evaluating the prognosis of patients with UTUC. AGR should be applied in UTUC patients for risk stratification and determination of optimal therapeutic regimens. PMID:26681341

  17. Impact of albumin on drug delivery--new applications on the horizon.

    PubMed

    Elsadek, Bakheet; Kratz, Felix

    2012-01-10

    Over the past decades, albumin has emerged as a versatile carrier for therapeutic and diagnostic agents, primarily for diagnosing and treating diabetes, cancer, rheumatoid arthritis and infectious diseases. Market approved products include fatty acid derivatives of human insulin or the glucagon-like-1 peptide (Levemir(®) and Victoza(®)) for treating diabetes, the taxol albumin nanoparticle Abraxane(®) for treating metastatic breast cancer which is also under clinical investigation in further tumor indications, and (99m)Tc-aggregated albumin (Nanocoll(®) and Albures(®)) for diagnosing cancer and rheumatoid arthritis as well as for lymphoscintigraphy. In addition, an increasing number of albumin-based or albumin-binding drugs are in clinical trials such as antibody fusion proteins (MM-111) for treating HER2/neu positive breast cancer (phase I), a camelid albumin-binding nanobody anti-HSA-anti-TNF-α (ATN-103) in phase II studies for treating rheumatoid arthritis, an antidiabetic Exendin-4 analog bound to recombinant human albumin (phase I/II), a fluorescein-labeled albumin conjugate (AFL)-human serum albumin for visualizing the malignant borders of brain tumors for improved surgical resection, and finally an albumin-binding prodrug of doxorubicin (INNO-206) entering phase II studies against sarcoma and gastric cancer. In the preclinical setting, novel approaches include attaching peptides with high-affinity for albumin to antibody fragments, the exploitation of albumin-binding gadolinium contrast agents for magnetic resonance imaging, and physical or covalent attachment of antiviral, antibacterial, and anticancer drugs to albumin that are permanently or transiently attached to human serum albumin (HSA) or act as albumin-binding prodrugs. This review gives an overview of the expanding field of preclinical and clinical drug applications and developments that use albumin as a protein carrier to improve the pharmacokinetic profile of the drug or to target the drug

  18. Protein extracts from cultured cells contain nonspecific serum albumin.

    PubMed

    Miyara, Masatsugu; Umeda, Kanae; Ishida, Keishi; Sanoh, Seigo; Kotake, Yaichiro; Ohta, Shigeru

    2016-06-01

    Serum is an important component of cell culture media. The present study demonstrates contamination of intracellular protein extract by bovine serum albumin from the culture media and illustrates how this contamination can cause the misinterpretation of western blot results. Preliminary experiments can prevent the misinterpretation of some experimental results, and optimization of the washing process may enable specific protein detection. PMID:26967711

  19. Albumin induced cytokine expression in porcine adipose tissue explants

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Albumin has historically been included in medium designed for use with adipose tissue when evaluating metabolism, gene expression or protein secretion. However, recent studies with mouse adipocytes (Ruan et al., J. Biol. Chem. 278:47585-47593, 2003) and human adipose tissue (Schlesinger et al., Ame...

  20. 21 CFR 862.1035 - Albumin test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Albumin test system. 862.1035 Section 862.1035 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems §...

  1. 21 CFR 862.1035 - Albumin test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Albumin test system. 862.1035 Section 862.1035 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems §...

  2. 21 CFR 862.1035 - Albumin test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Albumin test system. 862.1035 Section 862.1035 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems §...

  3. 21 CFR 862.1035 - Albumin test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Albumin test system. 862.1035 Section 862.1035 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems §...

  4. 21 CFR 862.1035 - Albumin test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Albumin test system. 862.1035 Section 862.1035 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems §...

  5. Interaction of purine bases and nucleosides with serum albumin

    NASA Astrophysics Data System (ADS)

    Sułkowska, A.; Michnik, A.

    1997-06-01

    The proton NMR spectra of alkyl derivatives of adenine and adenosine have been studied. High-resolution (400 MHz) proton spectra were recorded at 300 K at increasing concentrations of serum albumin. The dependence of the chemical shifts and the line width of the individual spectral lines on the protein concentration provides some detailed information about the nature of the complexes between the purine derivatives and albumin. Comparison of data for the methylated and non-methylated purine bases and nucleosides indicates the formation of non-specific complexes with serum albumin. However, the presence of the ethyl group in 8-ethyl-9 N-methyladenine means that in the adenine derivative-serum albumin complex the ethyl chain preserves its dominant role in binding. An advantage of our model is that the π-π interaction between the adenine ring and the amino acids of the protein can be replaced by hydrophobic interaction in the case of complexation of the ethyl adenine derivative.

  6. Point substitutions in albumin genetic variants from Asia.

    PubMed Central

    Arai, K; Madison, J; Shimizu, A; Putnam, F W

    1990-01-01

    Despite their rarity and physiologically neutral character, more inherited structural variants of serum albumin (alloalbumins) are known than for any other human protein except hemoglobin. Including three previously unreported examples described here, we have identified 13 different point substitutions in alloalbumins of Japanese origin. Of these only albumin B and two proalbumins have been reported in other ethnic groups, and these are the most common variants of European origin. Some alloalbumins of Asiatic origin, but not yet identified in Japanese, are present in diverse ethnic groups. An alloalbumin found in indigenes of New Guinea (lysine----asparagine at position 313) is also present in Caucasians of various European descents. Albumin Lambadi, occurring in a tribal group in south India, has a mutation (glutamic acid----lysine at position 501) also found as a rare variant in individuals of diverse ethnic origin resident on four continents. These results suggest that some alloalbumins with the same substitution may have originated by independent mutations in various populations. This, together with the apparent clustering of point substitutions in the protein structure, may reflect hypermutability of the albumin gene. PMID:2404284

  7. Decreased albumin mRNA in immunodeficient wasted' mice

    SciTech Connect

    Libertin, C.R.; Buczek, N.; Weaver, P.; Mobarhan, S.; Woloschak, G.E. Argonne National Lab., IL )

    1991-03-15

    Mice bearing the autosomal recessive gene wst (wst/wst) develop a wasting syndrome' that leads to death by 28-32 days of age. These mice have faulty repair of damage induced by ionizing radiation, immunodeficiency at secretory sites, and neurologic abnormalities. In addition to a progressively more apparent wasted phenotype, wst/wst mice show other features of failure to thrive and malnutrition. Daily body weights of the animals revealed a loss in weight between 25 and 30 days of age, a time during which normal littermates were progressively and rapidly gaining weight. Albumin mRNA levels were measured by dilution dot blot hybridizations of liver-derived RNA preparations from wasted mice, littermates, and parental controls. In all wasted mice, albumin mRNA levels were reduced 5 to 10 fold compared to controls. Northern blots revealed that the albumin mRNA present in wasted mice was normal in length though reduced in amount. These results suggest there may be a relationship between low albumin synthesis and the wasting syndrome of the wst/wst mouse.

  8. Spontaneous formation of small sized albumin/acacia coacervate particles.

    PubMed

    Burgess, D J; Singh, O N

    1993-07-01

    Microgel coacervate particles form spontaneously on mixing aqueous solutions of oppositely charged albumin and acacia, under specific conditions of pH, ionic strength, and polyion concentration, close to but not at the optimum conditions for maximum coacervate yield. The mean particle diameter of these coacervate particles is approximately 6 microns when suspended in aqueous media, as determined by HIAC/Royco particle analysis. The geometric standard deviation of the particles falls in the range 1.2-1.9 microns. The particle size was not dependent on the method of emulsification of the coacervate in the equilibrium phase, or on the stirring speed applied during the manufacturing process. The microgel particles were stable on storage, for periods up to forty-six days, without the addition of a chemical cross-linking agent, or the application of heat. Stability was measured with respect to the change in particle size of samples stored at different temperatures. The non-cross-linked microcapsules were also shown to be stable on pH change, to pH values outside the coacervation pH range. At the optimum conditions for maximum coacervate yield the albumin/acacia system formed a very viscous coacervate phase, which was unsuitable for microcapsule preparation. The rheological properties of albumin/acacia and gelatin/acacia complex coacervates optimized for maximum coacervate yield were compared. The albumin/acacia coacervate was shown to be three orders of magnitude more viscous than the gelatin/acacia system. PMID:8105049

  9. Separation of Albumin, Ceruloplasmin, and Transferrin from Human Plasma.

    ERIC Educational Resources Information Center

    Barnes, Grady; Frieden, Earl

    1982-01-01

    Procedures are provided for separating the principal metalloproteins (albumin, ceruloplasmin, and transferrin) from plasma using column chromatographic techniques. The experiment can be completed in two separate three-hour laboratory periods during which column chromatography is illustrated and the effect of pH on charge and affinity of a protein…

  10. Lipid-rich bovine serum albumin improves the viability and hatching ability of porcine blastocysts produced in vitro

    PubMed Central

    SUZUKI, Chie; SAKAGUCHI, Yosuke; HOSHI, Hiroyoshi; YOSHIOKA, Koji

    2015-01-01

    The effects of lipid-rich bovine serum albumin (LR-BSA) on the development of porcine blastocysts produced in vitro were examined. Addition of 0.5 to 5 mg/ml LR-BSA to porcine blastocyst medium (PBM) from Day 5 (Day 0 = in vitro fertilization) significantly increased the hatching rates of blastocysts on Day 7 and the total cell numbers in Day-7 blastocysts. When Day-5 blastocysts were cultured with PBM alone, PBM containing LR-BSA, recombinant human serum albumin or fatty acid-free BSA, addition of LR-BSA significantly enhanced hatching rates and the cell number in blastocysts that survived compared with other treatments. The diameter, ATP content and numbers of both inner cell mass and total cells in Day-6 and Day-7 blastocysts cultured with PBM containing LR-BSA were significantly higher than in blastocysts cultured with PBM alone, whereas LR-BSA had no effect on mitochondrial membrane potential. The mRNA levels of enzymes involved in fatty acid metabolism and β-oxidation (ACSL1, ACSL3, CPT1, CPT2 and KAT) in Day-7 blastocysts were significantly upregulated by the addition of LR-BSA. The results indicated that LR-BSA enhanced hatching ability and quality of porcine blastocysts produced in vitro, as determined by ATP content, blastocyst diameter and expression levels of the specific genes, suggesting that the stimulatory effects of LR-BSA arise from lipids bound to albumin. PMID:26582048

  11. Comparison of hetastarch to albumin for perioperative bleeding in patients undergoing abdominal aortic aneurysm surgery. A prospective, randomized study.

    PubMed Central

    Gold, M S; Russo, J; Tissot, M; Weinhouse, G; Riles, T

    1990-01-01

    The effects of hetastarch and human albumin solutions on perioperative bleeding and coagulation parameters during abdominal aortic aneurysm repair were compared. In two randomized groups of 20 patients, albumin 5% (group 1) or hetastarch 6% (group 2) 1 g/kg was given during surgery. The remaining perioperative fluids consisted of lactated ringers and packed red blood cells. Perioperative coagulation measurements included partial thromboplastin time, prothrombin time, activated clotting time, platelet count, and bleeding time. Estimated blood loss and the total amount of crystalloid and blood infused were also measured. The surgeon, blind to the colloid used, subjectively rated bleeding on a scale of 1 to 10. There was no significant difference between groups for any measured parameter at any time. Measurements of coagulation function were within normal limits for both groups. Hetastarch does not cause clotting disorders in patients undergoing abdominal aortic aneurysm repair, at least if the quantities used in this study are not exceeded. PMID:1690974

  12. 21 CFR 862.1645 - Urinary protein or albumin (nonquantitative) test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Urinary protein or albumin (nonquantitative) test... Chemistry Test Systems § 862.1645 Urinary protein or albumin (nonquantitative) test system. (a) Identification. A urinary protein or albumin (nonquantitative) test system is a device intended to...

  13. 21 CFR 862.1645 - Urinary protein or albumin (nonquantitative) test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Urinary protein or albumin (nonquantitative) test... Chemistry Test Systems § 862.1645 Urinary protein or albumin (nonquantitative) test system. (a) Identification. A urinary protein or albumin (nonquantitative) test system is a device intended to...

  14. 21 CFR 862.1645 - Urinary protein or albumin (nonquantitative) test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Urinary protein or albumin (nonquantitative) test... Chemistry Test Systems § 862.1645 Urinary protein or albumin (nonquantitative) test system. (a) Identification. A urinary protein or albumin (nonquantitative) test system is a device intended to...

  15. 21 CFR 862.1645 - Urinary protein or albumin (nonquantitative) test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Urinary protein or albumin (nonquantitative) test... Chemistry Test Systems § 862.1645 Urinary protein or albumin (nonquantitative) test system. (a) Identification. A urinary protein or albumin (nonquantitative) test system is a device intended to...

  16. 21 CFR 862.1645 - Urinary protein or albumin (nonquantitative) test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Urinary protein or albumin (nonquantitative) test... Chemistry Test Systems § 862.1645 Urinary protein or albumin (nonquantitative) test system. (a) Identification. A urinary protein or albumin (nonquantitative) test system is a device intended to...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Albumin is the most abundant protein found in healing wounds. Traditional and chromatogrpahic 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 dressin...

  18. Uptake of palmitate by hepatocyte suspensions: facilitation by albumin?

    PubMed

    Pond, S M; Davis, C K; Bogoyevitch, M A; Gordon, R A; Weisiger, R A; Bass, L

    1992-05-01

    Albumin-dependent uptake of unbound [3H]palmitic acid by hepatocytes isolated from female rat livers was studied and the experimental results compared with the predictions of a noncompartmental diffusion-reaction theory for the cellular uptake of protein-bound ligands. The outright theoretical predictions involve values for the parameters of the system, some newly measured (hepatocyte radii and the rate constant for the dissociation of palmitate-albumin complex) and some taken from the literature (diffusion coefficients and the equilibrium association constant for the palmitate-albumin complex). The measured unbound clearance of [3H]palmitic acid, defined as the initial uptake velocity divided by the unbound [3H]palmitic acid concentration in the medium, was enhanced 6.6-fold as the concentration of human serum albumin was increased from approximately 5 to 480 microM. This enhancement factor was predicted by the theory, according to which the enhancement reflects codiffusion of bound ligand across the unstirred layer adjacent to the cell membrane and, therefore, an increased delivery of unbound ligand to the cell surface. In contrast, the absolute magnitude of the unbound clearance was consistent with the theory only for the lowest published value for the equilibrium association constant, 15 microM-1. For higher published values (62 and 94 microM-1), the magnitude of the unbound clearance observed experimentally was severalfold higher than that predicted by the theory. If in fact the association constant exceeds 30 microM-1, the data would imply that an albumin-dependent facilitation mechanism exists which enhances the availability of palmitate to the cell over and above the enhancement predicted by the diffusion-reaction theory. PMID:1590397

  19. Albumin testing in urine using a smart-phone

    PubMed Central

    Coskun, Ahmet F.; Nagi, Richie; Sadeghi, Kayvon; Phillips, Stephen; Ozcan, Aydogan

    2013-01-01

    We demonstrate a digital sensing platform, termed Albumin Tester, running on a smart-phone that images and automatically analyses fluorescent assays confined within disposable test tubes for sensitive and specific detection of albumin in urine. This light-weight and compact Albumin Tester attachment, weighing approximately 148 grams, is mechanically installed on the existing camera unit of a smart-phone, where test and control tubes are inserted from the side and are excited by a battery powered laser diode. This excitation beam, after probing the sample of interest located within the test tube, interacts with the control tube, and the resulting fluorescent emission is collected perpendicular to the direction of the excitation, where the cellphone camera captures the images of the fluorescent tubes through the use of an external plastic lens that is inserted between the sample and the camera lens. The acquired fluorescent images of the sample and control tubes are digitally processed within one second through an Android application running on the same cellphone for quantification of albumin concentration in urine specimen of interest. Using a simple sample preparation approach which takes ~ 5 minutes per test (including the incubation time), we experimentally confirmed the detection limit of our sensing platform as 5–10 μg/mL (which is more than 3 times lower than clinically accepted normal range) in buffer as well as urine samples. This automated albumin testing tool running on a smart-phone could be useful for early diagnosis of kidney disease or for monitoring of chronic patients, especially those suffering from diabetes, hypertension, and/or cardiovascular diseases. PMID:23995895

  20. Albumin testing in urine using a smart-phone.

    PubMed

    Coskun, Ahmet F; Nagi, Richie; Sadeghi, Kayvon; Phillips, Stephen; Ozcan, Aydogan

    2013-11-01

    We demonstrate a digital sensing platform, termed Albumin Tester, running on a smart-phone that images and automatically analyses fluorescent assays confined within disposable test tubes for sensitive and specific detection of albumin in urine. This light-weight and compact Albumin Tester attachment, weighing approximately 148 grams, is mechanically installed on the existing camera unit of a smart-phone, where test and control tubes are inserted from the side and are excited by a battery powered laser diode. This excitation beam, after probing the sample of interest located within the test tube, interacts with the control tube, and the resulting fluorescent emission is collected perpendicular to the direction of the excitation, where the cellphone camera captures the images of the fluorescent tubes through the use of an external plastic lens that is inserted between the sample and the camera lens. The acquired fluorescent images of the sample and control tubes are digitally processed within one second through an Android application running on the same cellphone for quantification of albumin concentration in the urine specimen of interest. Using a simple sample preparation approach which takes ~5 min per test (including the incubation time), we experimentally confirmed the detection limit of our sensing platform as 5-10 μg mL(-1) (which is more than 3 times lower than the clinically accepted normal range) in buffer as well as urine samples. This automated albumin testing tool running on a smart-phone could be useful for early diagnosis of kidney disease or for monitoring of chronic patients, especially those suffering from diabetes, hypertension, and/or cardiovascular diseases. PMID:23995895

  1. Renal Type A Intercalated Cells Contain Albumin in Organelles with Aldosterone-Regulated Abundance

    PubMed Central

    Jensen, Thomas Buus; Cheema, Muhammad Umar; Szymiczek, Agata; Damkier, Helle Hasager; Praetorius, Jeppe

    2015-01-01

    Albumin has been identified in preparations of renal distal tubules and collecting ducts by mass spectrometry. This study aimed to establish whether albumin was a contaminant in those studies or actually present in the tubular cells, and if so, identify the albumin containing cells and commence exploration of the origin of the intracellular albumin. In addition to the expected proximal tubular albumin immunoreactivity, albumin was localized to mouse renal type-A intercalated cells and cells in the interstitium by three anti-albumin antibodies. Albumin did not colocalize with markers for early endosomes (EEA1), late endosomes/lysosomes (cathepsin D) or recycling endosomes (Rab11). Immuno-gold electron microscopy confirmed the presence of albumin-containing large spherical membrane associated bodies in the basal parts of intercalated cells. Message for albumin was detected in mouse renal cortex as well as in a wide variety of other tissues by RT-PCR, but was absent from isolated connecting tubules and cortical collecting ducts. Wild type I MDCK cells showed robust uptake of fluorescein-albumin from the basolateral side but not from the apical side when grown on permeable support. Only a subset of cells with low peanut agglutinin binding took up albumin. Albumin-aldosterone conjugates were also internalized from the basolateral side by MDCK cells. Aldosterone administration for 24 and 48 hours decreased albumin abundance in connecting tubules and cortical collecting ducts from mouse kidneys. We suggest that albumin is produced within the renal interstitium and taken up from the basolateral side by type-A intercalated cells by clathrin and dynamin independent pathways and speculate that the protein might act as a carrier of less water-soluble substances across the renal interstitium from the capillaries to the tubular cells. PMID:25874770

  2. Laser nanostructuring 3-D bioconstruction based on carbon nanotubes in a water matrix of albumin

    NASA Astrophysics Data System (ADS)

    Gerasimenko, Alexander Y.; Ichkitidze, Levan P.; Podgaetsky, Vitaly M.; Savelyev, Mikhail S.; Selishchev, Sergey V.

    2016-04-01

    3-D bioconstructions were created using the evaporation method of the water-albumin solution with carbon nanotubes (CNTs) by the continuous and pulsed femtosecond laser radiation. It is determined that the volume structure of the samples created by the femtosecond radiation has more cavities than the one created by the continuous radiation. The average diameter for multi-walled carbon nanotubes (MWCNTs) samples was almost two times higher (35-40 nm) than for single-walled carbon nanotubes (SWCNTs) samples (20-30 nm). The most homogenous 3-D bioconstruction was formed from MWCNTs by the continuous laser radiation. The hardness of such samples totaled up to 370 MPa at the nanoscale. High strength properties and the resistance of the 3-D bioconstructions produced by the laser irradiation depend on the volume nanotubes scaffold forming inside them. The scaffold was formed by the electric field of the directed laser irradiation. The covalent bond energy between the nanotube carbon molecule and the oxygen of the bovine serum albumin aminoacid residue amounts 580 kJ/mol. The 3-D bioconstructions based on MWCNTs and SWCNTs becomes overgrown with the cells (fibroblasts) over the course of 72 hours. The samples based on the both types of CNTs are not toxic for the cells and don't change its normal composition and structure. Thus the 3-D bioconstructions that are nanostructured by the pulsed and continuous laser radiation can be applied as implant materials for the recovery of the connecting tissues of the living body.

  3. Increased nutritive value of transgenic potato by expressing a nonallergenic seed albumin gene from Amaranthus hypochondriacus.

    PubMed

    Chakraborty, S; Chakraborty, N; Datta, A

    2000-03-28

    Improvement of nutritive value of crop plants, in particular the amino acid composition, has been a major long-term goal of plant breeding programs. Toward this end, we reported earlier the cloning of the seed albumin gene AmA1 from Amaranthus hypochondriacus. The AmA1 protein is nonallergenic in nature and is rich in all essential amino acids, and the composition corresponds well with the World Health Organization standards for optimal human nutrition. In an attempt to improve the nutritional value of potato, the AmA1 coding sequence was successfully introduced and expressed in tuber-specific and constitutive manner. There was a striking increase in the growth and production of tubers in transgenic populations and also of the total protein content with an increase in most essential amino acids. The expressed protein was localized in the cytoplasm as well as in the vacuole of transgenic tubers. Thus we have been able to use a seed albumin gene with a well-balanced amino acid composition as a donor protein to develop a transgenic crop plant. The results document, in addition to successful nutritional improvement of potato tubers, the feasibility of genetically modifying other crop plants with novel seed protein composition. PMID:10716698

  4. Study on the interaction of the toxic food additive carmoisine with serum albumins: a microcalorimetric investigation.

    PubMed

    Basu, Anirban; Kumar, Gopinatha Suresh

    2014-05-30

    The interaction of the synthetic azo dye and food colorant carmoisine with human and bovine serum albumins was studied by microcalorimetric techniques. A complete thermodynamic profile of the interaction was obtained from isothermal titration calorimetry studies. The equilibrium constant of the complexation process was of the order of 10(6)M(-1) and the binding stoichiometry was found to be 1:1 with both the serum albumins. The binding was driven by negative standard molar enthalpy and positive standard molar entropy contributions. The binding affinity was lower at higher salt concentrations in both cases but the same was dominated by mostly non-electrostatic forces at all salt concentrations. The polyelectrolytic forces contributed only 5-8% of the total standard molar Gibbs energy change. The standard molar enthalpy change enhanced whereas the standard molar entropic contribution decreased with rise in temperature but they compensated each other to keep the standard molar Gibbs energy change almost invariant. The negative standard molar heat capacity values suggested the involvement of a significant hydrophobic contribution in the complexation process. Besides, enthalpy-entropy compensation phenomenon was also observed in both the systems. The thermal stability of the serum proteins was found to be remarkably enhanced on binding to carmoisine. PMID:24742664

  5. Synthesis and characterization of imprinted sorbent for separation of gramine from bovine serum albumin.

    PubMed

    Luliński, Piotr; Klejn, Dorota; Maciejewska, Dorota

    2016-08-01

    The aim of this study was to develop an efficient sorbent for separation of N,N-dimethyl-3-aminomethylindole (gramine) from bovine serum albumin. An imprinting technology was involved in the synthesis of polymers from nine different functional monomers in the presence of ethylene glycol dimethacrylate as a cross-linker. The analysis of binding capacities showed that the highest specificity towards gramine was achieved when 4-vinylbenzoic acid was used as the functional monomer in methanol to form the bulk imprinted polymer, MIP1 (imprinting factor equal to 21.3). The Scatchard analysis of MIP1 showed two classes of binding sites with the dissociation constants Kd equal to 0.105 and 6.52μmolL(-1). The composition and morphology of polymers were defined by (13)C CP/MAS NMR, BET and SEM-EDS analyses. The recognition mechanism of MIP1 was tested using the structurally related bioanalytes, and the dominant role of indole moiety and ethylamine side chain was revealed. A new MISPE protocol was optimized for separation of gramine. The total recoveries on MIP1 were equal to 94±12 % from standard solutions and 85±11 % from bovine serum albumin. PMID:27157767

  6. Vanillin restrains non-enzymatic glycation and aggregation of albumin by chemical chaperone like function.

    PubMed

    Awasthi, Saurabh; Saraswathi, N T

    2016-06-01

    Vanillin a major component of vanilla bean extract is commonly used a natural flavoring agent. Glycation is known to induce aggregation and fibrillation of globular proteins such as albumin, hemoglobin. Here we report the inhibitory potential of vanillin toward early and advanced glycation modification and amyloid like aggregation of albumin based on the determination of both early and advanced glycation and conformational changes in albumin using circular dichroism. Inhibition of aggregation and fibrillation of albumin was determined based on amyloid specific dyes i.e., Congo red and Thioflavin T and microscopic imaging. It was evident that vanillin restrains glycation of albumin and exhibits protective effect toward its native conformation. PMID:26893056

  7. A Monoclonal IgM Protein with Antibody-like Activity for Human Albumin

    PubMed Central

    Hauptman, Stephen; Tomasi, Thomas B.

    1974-01-01

    The serum of a patient (L'ec) with an IgM lambda monoclonal protein was noted to bind albumin on immunoelectrophoresis. Analytical ultracentrifugation of the L'ec serum demonstrated 23S and 12S peaks, but no 4S (albumin) boundary. Immunologically identical 20S and 9S IgM proteins were isolated from the serum and the addition in vitro of either the patient's albumin or albumin isolated from normal serum was shown to reconstitute the 23S and 12S boundaries. The binding of high molecular weight IgM to albumin was demonstated by Sephadex G200 chromatography with 125I-labeled albumin and isolated IgM. Immunoelectrophoresis of the L'ec IgM developed with aggregated albumin (reverse immunoelectrophoresis) also demonstrated the binding of albumin to IgM. That all of the patient's IgM complexed with albumin was shown by affinity chromatography employing an aggregated albumin-immunoadsorbent column. Binding was shown to be of the noncovalent type by polyacrylamide gel electrophoresis in 8 M urea. With hot trypsin proteolysis, Fabμ and Fcμ5 fragments were isolated, and monomer albumin was shown to complex only with the Fabμ fragment by both analytical ultracentrifugation and molecular sieve chromatogaphy employing 125I-labeled Fab fragments. 1 mol of Fabμ fragment bound 1 mol of monomer albumin. Polymers of human albumin, produced by heat aggregation, precipitated with the isolated L'ec protein on gel diffusion analysis and, when coated on sheep red blood cells, gave a hemagglutination titer greater than 1 million with the whole L'ec serum. 50 additional monoclonal IgM, 33 IgA, and 80 IgG sera failed to show precipitation or hemagglutination with aggregated albumin. Native monomer albumin inhibited precipitation only at high concentrations (> 50 mg/ml); dimer albumin or fragments of albumin produced by trypsin digestion inhibited at low concentrations (0.4 mg/ml). No reactivity occurred with the albumin of five other mammalian species, including bovine. The L'ec protein

  8. Buoyancy-activated cell sorting using targeted biotinylated albumin microbubbles.

    PubMed

    Liou, Yu-Ren; Wang, Yu-Hsin; Lee, Chia-Ying; Li, Pai-Chi

    2015-01-01

    Cell analysis often requires the isolation of certain cell types. Various isolation methods have been applied to cell sorting, including fluorescence-activated cell sorting and magnetic-activated cell sorting. However, these conventional approaches involve exerting mechanical forces on the cells, thus risking cell damage. In this study we applied a novel isolation method called buoyancy-activated cell sorting, which involves using biotinylated albumin microbubbles (biotin-MBs) conjugated with antibodies (i.e., targeted biotin-MBs). Albumin MBs are widely used as contrast agents in ultrasound imaging due to their good biocompatibility and stability. For conjugating antibodies, biotin is conjugated onto the albumin MB shell via covalent bonds and the biotinylated antibodies are conjugated using an avidin-biotin system. The albumin microbubbles had a mean diameter of 2 μm with a polydispersity index of 0.16. For cell separation, the MDA-MB-231 cells are incubated with the targeted biotin-MBs conjugated with anti-CD44 for 10 min, centrifuged at 10 g for 1 min, and then allowed 1 hour at 4 °C for separation. The results indicate that targeted biotin-MBs conjugated with anti-CD44 antibodies can be used to separate MDA-MB-231 breast cancer cells; more than 90% of the cells were collected in the MB layer when the ratio of the MBs to cells was higher than 70:1. Furthermore, we found that the separating efficiency was higher for targeted biotin-MBs than for targeted avidin-incorporated albumin MBs (avidin-MBs), which is the most common way to make targeted albumin MBs. We also demonstrated that the recovery rate of targeted biotin-MBs was up to 88% and the sorting purity was higher than 84% for a a heterogenous cell population containing MDA-MB-231 cells (CD44(+)) and MDA-MB-453 cells (CD44-), which are classified as basal-like breast cancer cells and luminal breast cancer cells, respectively. Knowing that the CD44(+) is a commonly used cancer-stem-cell biomarker, our

  9. Buoyancy-Activated Cell Sorting Using Targeted Biotinylated Albumin Microbubbles

    PubMed Central

    Liou, Yu-Ren; Wang, Yu-Hsin; Lee, Chia-Ying; Li, Pai-Chi

    2015-01-01

    Cell analysis often requires the isolation of certain cell types. Various isolation methods have been applied to cell sorting, including florescence-activated cell sorting and magnetic-activated cell sorting. However, these conventional approaches involve exerting mechanical forces on the cells, thus risking cell damage. In this study we applied a novel isolation method called buoyancy-activated cell sorting, which involves using biotinylated albumin microbubbles (biotin-MBs) conjugated with antibodies (i.e., targeted biotin-MBs). Albumin MBs are widely used as contrast agents in ultrasound imaging due to their good biocompatibility and stability. For conjugating antibodies, biotin is conjugated onto the albumin MB shell via covalent bonds and the biotinylated antibodies are conjugated using an avidin-biotin system. The albumin microbubbles had a mean diameter of 2μm with a polydispersity index of 0.16. For cell separation, the MDA-MB-231 cells are incubated with the targeted biotin-MBs conjugated with anti-CD44 for 10 min, centrifuged at 10g for 1 min, and then allowed 1 hour at 4°C for separation. The results indicate that targeted biotin-MBs conjugated with anti-CD44 antibodies can be used to separate MDA-MB-231 breast cancer cells; more than 90% of the cells were collected in the MB layer when the ratio of the MBs to cells was higher than 70:1. Furthermore, we found that the separating efficiency was higher for targeted biotin-MBs than for targeted avidin-incorporated albumin MBs (avidin-MBs), which is the most common way to make targeted albumin MBs. We also demonstrated that the recovery rate of targeted biotin-MBs was up to 88% and the sorting purity was higher than 84% for a a heterogenous cell population containing MDA-MB-231 cells (CD44+) and MDA-MB-453 cells (CD44–), which are classified as basal-like breast cancer cells and luminal breast cancer cells, respectively. Knowing that the CD44+ is a commonly used cancer-stem-cell biomarker, our targeted

  10. Serum albumin analysis for type II diabetes detection using surface-enhanced Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Lin, Jinyong; Cao, Gang; Lin, Juqiang; Liu, Nenrong; Liao, Fadian; Ruan, Qiuyong; Wu, Shanshan; Huang, Zufang; Li, Ling; Chen, Rong

    2014-09-01

    Surface-enhanced Raman scattering (SERS) spectroscopy combined with membrane electrophoresis (ME) was firstly employed to detect albumin variation in type II diabetic development. Albumin was first purified from human serum by ME and then mixed with silver nanoparticles to perform SERS spectral analysis. SERS spectra were obtained from blood albumin samples of 20 diabetic patients and 19 healthy volunteers. Subtle but discernible changes in the acquired mean spectra of the two groups were observed. Tentative assignment of albumin SERS bands indicated specific structural changes of albumin molecule with diabetic development. Meanwhile, PCA-LDA diagnostic algorithms were employed to classify the two kinds of albumin SERS spectra, yielding the diagnostic sensitivity of 90% and specificity of 94.7%. The results from this exploratory study demonstrated that the EM-SERS method in combination with multivariate statistical analysis has great potential for the label-free detection of albumin variation for improving type II diabetes screening.

  11. Insulin Is Required to Maintain Albumin Expression by Inhibiting Forkhead Box O1 Protein.

    PubMed

    Chen, Qing; Lu, Mingjian; Monks, Bobby R; Birnbaum, Morris J

    2016-01-29

    Diabetes is accompanied by dysregulation of glucose, lipid, and protein metabolism. In recent years, much effort has been spent on understanding how insulin regulates glucose and lipid metabolism, whereas the effect of insulin on protein metabolism has received less attention. In diabetes, hepatic production of serum albumin decreases, and it has been long established that insulin positively controls albumin gene expression. In this study, we used a genetic approach in mice to identify the mechanism by which insulin regulates albumin gene transcription. Albumin expression was decreased significantly in livers with insulin signaling disrupted by ablation of the insulin receptor or Akt. Concomitant deletion of Forkhead Box O1 (Foxo1) in these livers rescued the decreased albumin secretion. Furthermore, activation of Foxo1 in the liver is sufficient to suppress albumin expression. These results suggest that Foxo1 acts as a repressor of albumin expression. PMID:26668316

  12. Factors Associated With Serum Albumin in Diabetes Mellitus Type 2 With Microalbuminuria Using Non-Normal Mixed Models: A Prospective Cohort Study

    PubMed Central

    Khoundabi, Batoul; Kazemnejad, Anoshirvan; Mansourian, Marjan; Faghihimani, Elham

    2016-01-01

    Background: The globally increasing epidemic of diabetes will lead to serious problems including diabetic nephropathy and kidney diseases in near future. The first clinical diagnosable stage in a diabetic kidney disease is microalbuminuria (urinary albumin excretion of 30 - 300 g/24 hours). Objectives: This prospective cohort study investigated the risk factors of microalbuminuria in patients with type 2 diabetes who had been registered in endocrine and metabolism research center in Isfahan city, Iran. Patients and Methods: This prospective cohort study was performed on 90 diabetic type 2 patients with microalbuminuria, who were selected according to the consecutive sample selection method during 6 years. Data were collected through regular and systematic measurements of serum albumin as the response variable and body mass index, systolic and diastolic blood pressure, the duration of diabetes, glycosylated hemoglobin (HbA1c), total cholesterol, triglyceride (TG), fasting blood sugar (FBS), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) as the related factors. Non-normal mixed models were used to investigate the impact of effective factors on the amount of excreted serum albumin. Results: According to the deviance information criterion (DIC = 56.2), the non-normal mixed effects model with the skewed t distribution had a best fit and indicated that HbA1c, HDL and total cholesterol had a significant effect on the amount of albumin in urine (P < 0.05). Conclusions: Using nonnormal mixed models may lead to the best results as compared to common normality assumption. PMID:26889385

  13. Absorptive-mediated endocytosis of cationized albumin and a beta-endorphin-cationized albumin chimeric peptide by isolated brain capillaries. Model system of blood-brain barrier transport

    SciTech Connect

    Kumagai, A.K.; Eisenberg, J.B.; Pardridge, W.M.

    1987-11-05

    Cationized albumin (pI greater than 8), unlike native albumin (pI approximately 4), enters cerebrospinal fluid (CSF) rapidly from blood. This suggests that a specific uptake mechanism for cationized albumin may exist at the brain capillary wall, i.e. the blood-brain barrier. Isolated bovine brain capillaries rapidly bound cationized (/sup 3/H)albumin and approximately 70% of the bound radioactivity was resistant to mild acid wash, which is assumed to represent internalized peptide. Binding was saturable and a Scatchard plot gave a maximal binding capacity (Ro) = 5.5 +/- 0.7 micrograms/mgp (79 +/- 10 pmol/mgp), and a half-saturation constant (KD) = 55 +/- 8 micrograms/ml (0.8 +/- 0.1 microM). The binding of cationized (/sup 3/H)albumin (pI = 8.5-9) was inhibited by protamine, protamine sulfate, and polylysine (molecular weight = 70,000) with a Ki of approximately 3 micrograms/ml for all three proteins. The use of cationized albumin in directed delivery of peptides through the blood-brain barrier was examined by coupling (/sup 3/H)beta-endorphin to unlabeled cationized albumin (pI = 8.5-9) using the bifunctional reagent, N-succinimidyl 3-(2-pyridyldithio)proprionate. The (/sup 3/H)beta-endorphin-cationized albumin chimeric peptide was rapidly bound and endocytosed by isolated bovine brain capillaries, and this was inhibited by unlabeled cationized albumin but not by unconjugated beta-endorphin or native bovine albumin. Cationized albumin provides a new tool for studying absorptive-mediated endocytosis at the brain capillary and may also provide a vehicle for directed drug delivery through the blood-brain barrier.

  14. Recent advancements in erythrocytes, platelets, and albumin as delivery systems

    PubMed Central

    Xu, Peipei; Wang, Ruju; Wang, Xiaohui; Ouyang, Jian

    2016-01-01

    In the past few years, nanomaterial-based drug delivery systems have been applied to enhance the efficacy of therapeutics and to alleviate negative effects through the controlled delivery of targeting and releasing agents. However, few drug carriers can achieve high targeting efficacy, even when targeting modalities and surface markers are introduced. Immunological problems have also limited their wide applications. Biological drug delivery systems, such as erythrocytes, platelets, and albumin, have been extensively investigated because of their unique properties. In this review, erythrocytes, platelets, and albumin are described as efficient drug delivery systems. Their properties, applications, advantages, and limitations in disease treatment are explained. This review confirms that these systems can be used to facilitate a specific, biocompatible, and smart drug delivery. PMID:27274282

  15. Recent topics in chemical and clinical research on glycated albumin.

    PubMed

    Ueda, Yuki; Matsumoto, Hideyuki

    2015-03-01

    The measuring method for glycated albumin (GA) has been developed as a new glycemic control marker since the beginning of the 21st century. Since GA has an advantage in reflecting glycemic status over a shorter period than hemoglobin A1c (HbA1c), much research and many reviews have been reported. However, so far there have been few reports on glycation sites based on the tertiary structure of human serum albumin (HSA) and the comparison of glycation rates between GA and HbA1c in detail. The present review discusses how the glycation sites of lysine residues in HSA are modified with glucose, whereas the glycation sites of lysine residues are located inside of HSA as well as the direct comparison of glycation rates between GA and HbA1c using human blood. Moreover, the most recent clinical researches on GA are described. PMID:25614014

  16. 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. PMID:25901656

  17. Curcumin-incorporated albumin nanoparticles and its tumor image

    NASA Astrophysics Data System (ADS)

    Gong, Guangming; Pan, Qinqin; Wang, Kaikai; Wu, Rongchun; Sun, Yong; Lu, Ying

    2015-01-01

    Albumin is an ideal carrier for hydrophobic drugs. This paper reports a facile route to develop human serum albumin (HSA)-curcumin (CCM) nanoparticles, in which β-mercaptoethanol (β-ME) acted as an inducer and CCM acted as a bridge. Fluorescence quenching and conformational changes in HSA-CCM nanoparticles occurred during assembly. Disulfide bonds and hydrophobic interactions may play a key role in assembly. HSA-CCM nanoparticles were about 130 nm in size, and the solubility of CCM increased by more than 500 times. The HSA-CCM nanoparticles could accumulate at the cytoplasm of tumor cells and target the tumor tissues. Therefore, HSA nanoparticles fabricated by β-ME denaturation are promising nanocarriers for hydrophobic substances from chemotherapy drugs to imaging probes.

  18. Iodide and albumin kinetics in normal canine wrists and knees

    SciTech Connect

    Simkin, P.A.; Benedict, R.S. )

    1990-01-01

    The clearance rates of free iodide and of radioiodinated serum albumin were measured in the knee and wrist joints of 9 normal adult dogs. Iodide clearance from the knee was 3 times greater than that from the wrist. In contrast, radioiodinated serum albumin clearance from the knee was only slightly greater than that from the wrist. Interpreted as respective indices of effective synovial plasma flow and lymphatic drainage, these values indicate that the filtration fraction is normally greater in microvessels of the wrist than in those of the knee. These findings complement the results of companion studies of Starling forces that indicate a higher pressure microvascular bed in the wrist than in the knee.

  19. Tamoxifen and curcumin binding to serum albumin. Spectroscopic study

    NASA Astrophysics Data System (ADS)

    Maciążek-Jurczyk, M.; Maliszewska, M.; Pożycka, J.; Równicka-Zubik, J.; Góra, A.; Sułkowska, A.

    2013-07-01

    Tamoxifen (TMX) is widely used for the breast cancer treatment and is known as chemopreventive agent. Curcumin (CUR) is natural phenolic compound with broad spectrum of biological activity e.g. anti-inflammatory, antimicrobial, antiviral, antifungal and chemopreventive. Combination of tamoxifen and curcumin could be more effective with lower toxicity than each agent alone in use for the treatment or chemoprevention of breast cancer. Binding of drugs to serum albumin is an important factor, which determines toxicity and therapeutic dosage of the drugs. When two drugs are administered together the competition between them for the binding site on albumin can result in a decrease in bound fraction and an increase in the concentration of free biologically active fraction of drug.

  20. The pretreatment albumin to globulin ratio predicts survival in patients with natural killer/T-cell lymphoma

    PubMed Central

    Bi, Xi-wen; Wang, Liang; Zhang, Wen-wen; Yan, Shu-mei; Sun, Peng; Xia, Yi; Li, Zhi-ming

    2016-01-01

    Background. The pretreatment albumin to globulin ratio (AGR) has been reported to be a predictor of survival in several types of cancer. The aim of this study was to evaluate the prognostic impact of AGR in patients with natural killer/T-cell lymphoma (NKTCL). Methods. We retrospectively reviewed the available serum biochemistry results for 331 NKTCL patients before treatment. AGR was calculated as albumin/(total protein—albumin), and a cut-off value of 1.3 was used to define AGR as low or high. Survival analysis was used to assess the prognostic value of AGR. Results. A low AGR (<1.3) was associated with significantly more adverse clinical features, including old age, poor performance status, advanced stage, elevated lactate dehydrogenase, B symptoms, and high International Prognostic Index (IPI) and natural killer/T-cell lymphoma prognostic index (NKPI) scores. Patients with a low AGR had a significantly lower 5-year overall survival (44.5 vs. 65.2%, P < 0.001) and progression-free survival (33.1 vs. 57.4%, P < 0.001). In the multivariate analysis, a low AGR remained an independent predictor of poorer survival. Additionally, AGR distinguished patients with different outcomes in the IPI low-risk group and in the NKPI high-risk group. Discussion. Pretreatment AGR may serve as a simple and effective predictor of prognosis in patients with NKTCL. PMID:26966671

  1. Substrate recycling scheme for tetrachloro-p-benzoquinone using bilirubin oxidase and NADH: Application for pentachlorophenol assay

    SciTech Connect

    Cybulski, D.; Luong, J.H.T.; Male, K.B.; Scharer, J.M.; Moo-Young, M.

    1999-03-01

    A novel assay for tetrachloro-p-benzoquinone (TCBQ), the main oxidation product of pentachlorophenol (PCP), was developed using bilirubin oxidase (BOX) in the presence of excess NADH. TCBQ was easily and rapidly reduced by NADH to 1,4-tetrachlorohydroquinone (TCHQ), which was then recycled back to TCBQ by the enzyme. BOX exhibited no reactivity toward NADH while its catalytic activity for the oxidation of TCHQ was very high. Under an optimized condition, the rate of NADH consumption determined by measuring the absorbance decrease at 340 nm yielded a detection limit for TCBQ of 110 nM. Fluorescence detection of the NADH using a lower enzyme concentration with excitation and emission wavelengths of 345 and 450 nm, respectively, allowed for a TCBQ detection limit of 30 nM. PCP was oxidized to TCBQ with high yield using bis(trifluoroacetoxy)iodobenzene in 0.05 M trichloroacetic acid. Coupling this oxidation reaction to the BOX/NADH assay attained PCT detection limits of 170 and 50 nM using absorbance and fluorescence measurements, respectively. When tested on PCP-contaminated soil samples, the BOX assay compared very well with HPLC measurements.

  2. Research Update: Facile synthesis of CoFe2O4 nano-hollow spheres for efficient bilirubin adsorption

    NASA Astrophysics Data System (ADS)

    Rakshit, Rupali; Pal, Monalisa; Chaudhuri, Arka; Mandal, Madhuri; Mandal, Kalyan

    2015-11-01

    Herein, we report an unprecedented bilirubin (BR) adsorption efficiency of CoFe2O4 (CFO) nanostructures in contrast to the commercially available activated carbon and resin which are generally used for haemoperfusion and haemodialysis. We have synthesized CFO nanoparticles of diameter 100 nm and a series of nano-hollow spheres of diameter 100, 160, 250, and 350 nm using a simple template free solvothermal technique through proper variation of reaction time and capping agent, oleylamine (OLA), respectively, and carried out SiO2 coating by employing Stöber method. The comparative BR adsorption study of CFO and SiO2 coated CFO nanostructures indicates that apart from porosity and hollow configuration of nanostructures, the electrostatic affinity between anionic carboxyl group of BR and cationic amine group of OLA plays a significant role in adsorbing BR. Finally, we demonstrate that the BR adsorption capacity of the nanostructures can be tailored by varying the morphology as well as size of the nanostructures. We believe that our developed magnetic nanostructures could be considered as a potential material towards therapeutic applications against hyperbilirubinemia.

  3. How the Intricate Interactions between Carbon Nanotubes and Two Bilirubin Oxidases Control Direct and Mediated O2 Reduction.

    PubMed

    Mazurenko, Ievgen; Monsalve, Karen; Rouhana, Jad; Parent, Philippe; Laffon, Carine; Goff, Alan Le; Szunerits, Sabine; Boukherroub, Rabah; Giudici-Orticoni, Marie-Thérèse; Mano, Nicolas; Lojou, Elisabeth

    2016-09-01

    Due to the lack of a valid approach in the design of electrochemical interfaces modified with enzymes for efficient catalysis, many oxidoreductases are still not addressed by electrochemistry. We report in this work an in-depth study of the interactions between two different bilirubin oxidases, (from the fungus Myrothecium verrucaria and from the bacterium Bacillus pumilus), catalysts of oxygen reduction, and carbon nanotubes bearing various surface charges (pristine, carboxylic-, and pyrene-methylamine-functionalized). The surface charges and dipole moment of the enzymes as well as the surface state of the nanomaterials are characterized as a function of pH. An original electrochemical approach allows determination of the best interface for direct or mediated electron transfer processes as a function of enzyme, nanomaterial type, and adsorption conditions. We correlate these experimental results to theoric voltammetric curves. Such an integrative study suggests strategies for designing efficient bioelectrochemical interfaces toward the elaboration of biodevices such as enzymatic fuel cells for sustainable electricity production. PMID:27533778

  4. Study of Model Systems for Bilirubin and Bilin Chromophores: Determination and Modification of Thermal and Photochemical Properties.

    PubMed

    García-Iriepa, Cristina; Ernst, Hanna A; Liang, Yu; Unterreiner, Andreas-Neil; Frutos, Luis Manuel; Sampedro, Diego

    2016-08-01

    Bilin chromophores and bilirubin are involved in relevant biological functions such as light perception in plants and as protective agents against Alzheimer and other diseases. Despite their extensive use, a deep rationalization of the main factors controlling the thermal and photochemical properties has not been performed yet, which in turn hampers further applications of these versatile molecules. In an effort to understand those factors and allow control of the relevant properties, a combined experimental and computational study has been carried out for diverse model systems to understand the interconversion between Z and E isomers. In this study, we have demonstrated the crucial role of steric hindrance and hydrogen-bond interactions in thermal stability and the ability to control them by designing novel compounds. We also determined several photochemical properties and studied the photodynamics of two model systems in more detail, observing a fast relaxation of the excited state shorter than 2 ps in both cases. Finally, the computational study allowed us to rationalize the experimental evidence. PMID:27391671

  5. Binding of several benzodiazepines to bovine serum albumin: Fluorescence study

    NASA Astrophysics Data System (ADS)

    Machicote, Roberta G.; Pacheco, María E.; Bruzzone, Liliana

    2010-10-01

    The interactions of lorazepam, oxazepam and bromazepam with bovine serum albumin (BSA) were studied by fluorescence spectrometry. The Stern-Volmer quenching constants and corresponding thermodynamic parameters Δ H, Δ G and Δ S were calculated. The binding constants and the number of binding sites were also investigated. The distances between the donor (BSA) and the acceptors (benzodiazepines) were obtained according to fluorescence resonance energy transfer and conformational changes of BSA were observed from synchronous fluorescence spectra.

  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. Cisplatin loaded albumin mesospheres for lung cancer treatment.

    PubMed

    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

  8. Reactions of trimethylphosphine analogues of auranofin with bovine serum albumin

    SciTech Connect

    Isab, A.A.; Shaw, C.F. III; Hoeschele, J.D.; Locke, J.

    1988-10-05

    The reactions of bovine serum albumin (BSA) with (trimethylphosphine)(2,3,4,6-tetra-O-acetyl-1-thio-..beta..-D-glucopyranosato-S)gold(I), Me/sub 3/PAuSAtg, and its chloro analogue, Me/sub 3/PAuCl, were studied to develop insights into the role of the phosphine ligand in the serum chemistry of the related antiarthritic drug auranofin (triethylphosphine)(2,3,4,6-tetra-O-acetyl-1-thio-..beta..-D-glucopyranosato-S)gold(I). /sup 31/P NMR spectroscopy, protein modification, and gel-exclusion chromatography methods were employed. Comparison of the reactions of the methyl derivatives to the previously reported reactions of auranofin and Et/sub 3/PAuCl with BSA demonstrated that similar chemical species are formed but revealed three major differences. Despite these differences, the results for the methyl analogues provide important confirmation for previously developed chemical models of auranofin reactions in serum. Me/sub 3/PO was not observed in reaction mixtures lacking tetraacetylthioglucose (AtgSH); this result affirms the role of AtgSH, displaced by the reaction of Me/sub 3/PAuSAtg at Cys-34, in the generation of the phosphine oxide (an important metabolite in vivo). The weak binding sites on albumin react with Me/sub 3/PAuCl, but not Me/sub 3/PAuSAtg, demonstrating the importance of the strength and reactivity of the anionic ligand-gold bond on the reactions of auranofin analogues. The gold binding capacity of albumin is enhanced after Me/sub 3/PO is formed, consistent with reductive cleavage of albumin disulfide bonds by trimethylphosphine. 24 references, 2 figures, 3 tables.

  9. 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. PMID:24970853

  10. Increased regional vascular albumin permeation in the rat during anaphylaxis

    SciTech Connect

    Leng, W.; Chang, K.; Williamson, J.R.; Jakschik, B.A.

    1989-03-15

    The changes in vascular albumin permeation induced by systemic anaphylaxis were studied simultaneously in 21 different tissues of the same animal. Before Ag challenge sensitized rats were injected i.v. with 125I-albumin (test tracer), 51Cr-RBC (vascular space marker) and 57Co-EDTA (extravascular space marker). The index of vascular permeation used was the tissue to blood isotope ratio (tbir), which was obtained by dividing the ratio of 125I/51Cr counts in each tissue by the ratio of the same isotopes in the arterial blood sample. After Ag challenge, the increase in the tbir varied considerably among the different tissues. The most pronounced increase was noted in the lymph node (ninefold) followed by the aorta and mesentery (six- to sevenfold) and the various parts of the gastrointestinal tract (four- to sixfold). In the skin less than skeletal muscle less than lung less than liver and eye two- to fourfold increases occurred. Relatively minor increases in albumin permeation (less than twofold) were observed in the brain less than kidney less than heart and less than spleen. The testis was the only organ in which no significant change occurred. For some of the tissues there was also an increase in the tbir for 57Co/51Cr (an index of the extracellular fluid space) suggesting edema formation. The highest increase was noted in the aorta (fourfold). Minor increases occurred in the atrium of the heart, stomach, duodenum, and lymph nodes. There was also a 36% increase in hematocrit. Therefore, systemic anaphylaxis caused extensive extravasation of albumin and hemoconcentration.

  11. The effect of premature and delayed birth on the development of UDP-glucuronosyltransferase activities towards bilirubin, morphine and testosterone in the rat.

    PubMed Central

    Campbell, M T; Wishart, G J

    1980-01-01

    In the rat, UDP-glucuronosyltransferase activities towards bilirubin, morphine and testosterone increase markedly after normal or premature birth. This rapid development is superimposed upon a much slower maturation of activity which occurs in utero during the last 2 days of normal gestation and gestation when birth is delayed. Development of all three activities is similar under these different conditions, suggesting a common developmenpal regulatory mechanism. PMID:6769435

  12. Early albumin infusion to infants at risk for respiratory distress

    PubMed Central

    Bland, R. D.; Clarke, T. L.; Harden, L. B.; Mayer, Judith L.; Ries, J. P.; Madden, W. A.; Crast, F. W.; Coyer, W. F.; Bass, J. W.

    1973-01-01

    In a randomized prospective study, 100 high-risk infants (selected on the basis of a cord serum protein level of 4·6 g/100 ml or less, gestational age under 37 weeks, birthweight 2500 g or less, and/or arterial pH below 7·25) received 8 ml/kg of either 25% salt-poor albumin or 5% dextrose in water before the age of 2 hours. All infants were then managed supportively with warmth, appropriate oxygen supplementation, isotonic fluid infusion, and close monitoring, without further administration of colloid or hypertonic alkali solutions over the first 4 hours of life. No statistically significant difference was shown between early colloid and early dextrose-water administration for either the incidence of idiopathic respiratory distress syndrome (RDS) or the mortality of high-risk infants, suggesting no apparent advantage of albumin over simple glucose-water infusion to hypoproteinaemic newborns shortly after birth. However, among the infants of 28 weeks' gestation or less admitted to the study, 3 of 4 albumin-treated patients survived, while 5 comparable infants in the dextrose-water group died within 12 hours of birth. For the 100 infants taken together there was a significant improvement in morbidity and mortality from previous experience in the same nursery, indicating that prompt supportive care, including early fluid administration, may be instrumental in reducing the incidence and severity of RDS. PMID:4749684

  13. Immunodetection of Serum Albumin Adducts as Biomarkers for Organophosphorus Exposure

    PubMed Central

    Chen, Sigeng; Zhang, Jun; Lumley, Lucille

    2013-01-01

    A major challenge in organophosphate (OP) research has been the identification and utilization of reliable biomarkers for the rapid, sensitive, and efficient detection of OP exposure. Although Tyr 411 OP adducts to human serum albumin (HSA) have been suggested to be one of the most robust biomarkers in the detection of OP exposure, the analysis of HSA-OP adduct detection has been limited to techniques using mass spectrometry. Herein, we describe the procurement of two monoclonal antibodies (mAb-HSA-GD and mAb-HSA-VX) that recognized the HSA Tyr 411 adduct of soman (GD) or S-[2-(diisopropylamino)ethyl]-O-ethyl methylphosphonothioate (VX), respectively, but did not recognize nonphosphonylated HSA. We showed that mAb-HSA-GD was able to detect the HSA Tyr 411 OP adduct at a low level (i.e., human blood plasma treated with 180 nM GD) that could not be detected by mass spectrometry. mAb-HSA-GD and mAb-HSA-VX showed an extremely low-level detection of GD adducted to HSA (on the order of picograms). mAb-HSA-GD could also detect serum albumin OP adducts in blood plasma samples from different animals administered GD, including rats, guinea pigs, and monkeys. The ability of the two antibodies to selectively recognize nerve agents adducted to serum albumin suggests that these antibodies could be used to identify biomarkers of OP exposure and provide a new biologic approach to detect OP exposure in animals. PMID:23192655

  14. Superior serum half life of albumin tagged TNF ligands

    SciTech Connect

    Mueller, Nicole; Schneider, Britta; Pfizenmaier, Klaus; Wajant, Harald

    2010-06-11

    Due to their immune stimulating and apoptosis inducing properties, ligands of the TNF family attract increasing interest as therapeutic proteins. A general limitation of in vivo applications of recombinant soluble TNF ligands is their notoriously rapid clearance from circulation. To improve the serum half life of the TNF family members TNF, TWEAK and TRAIL, we genetically fused soluble variants of these molecules to human serum albumin (HSA). The serum albumin-TNF ligand fusion proteins were found to be of similar bioactivity as the corresponding HSA-less counterparts. Upon intravenous injection (i.v.), serum half life of HSA-TNF ligand fusion proteins, as determined by ELISA, was around 15 h as compared to approximately 1 h for all of the recombinant control TNF ligands without HSA domain. Moreover, serum samples collected 6 or 24 h after i.v. injection still contained high TNF ligand bioactivity, demonstrating that there is only limited degradation/inactivation of circulating HSA-TNF ligand fusion proteins in vivo. In a xenotransplantation model, significantly less of the HSA-TRAIL fusion protein compared to the respective control TRAIL protein was required to achieve inhibition of tumor growth indicating that the increased half life of HSA-TNF ligand fusion proteins translates into better therapeutic action in vivo. In conclusion, our data suggest that genetic fusion to serum albumin is a powerful and generally applicable mean to improve bioavailability and in vivo activity of TNF ligands.

  15. Albumin extravasation rates in tissues of anesthetized and unanesthetized rats

    SciTech Connect

    Renkin, E.M.; Joyner, W.L.; Gustafson-Sgro, M.; Plopper, G.; Sibley, L.

    1989-05-01

    Bovine serum albumin (BSA) labeled with /sup 131/I was injected intravenously in chronically prepared, unanesthetized rats and into pentobarbital-anesthetized rats that had received 2 ml 5% BSA to help sustain plasma volume. Initial uptake rates (clearances) in skin, skeletal muscles, diaphragm, and heart (left ventricle) were measured over 1 h. BSA labeled with /sup 125/I was injected terminally to correct for intravascular /sup 131/I-BSA. Observed clearances were in the following order in both groups of animals: heart much greater than diaphragm approximately equal to skin greater than resting skeletal muscles. Differences between unanesthetized and anesthetized animals were small and inconsistently directed. Our results suggest that the lower albumin clearances reported in the literature for anesthetized rats are not the result of their immobility or any direct effect of anesthesia on albumin transport in these tissues. The lower transport rates appear to result indirectly from changes produced by anesthesia and/or surgery in controllable parameters such as plasma volume and intravascular protein mass.

  16. Pru du 2S albumin or Pru du vicilin?

    PubMed

    Garino, Cristiano; De Paolis, Angelo; Coïsson, Jean Daniel; Arlorio, Marco

    2015-06-01

    A short partial sequence of 28 amino acids is all the information we have so far about the putative allergen 2S albumin from almond. The aim of this work was to analyze this information using mainly bioinformatics tools, in order to verify its rightness. Based on the results reported in the paper describing this allergen from almond, we analyzed the original data of amino acids sequencing through available software. The degree of homology of the almond 12kDa protein with any other known 2S albumin appears to be much lower than the one reported in the paper that firstly described it. In a publicly available cDNA library we discovered an expressed sequence tag which translation generates a protein that perfectly matches both of the sequencing outputs described in the same paper. A further analysis indicated that the latter protein seems to belong to the vicilin superfamily rather than to the prolamin one. The fact that also vicilins are seed storage proteins known to be highly allergenic would explain the IgE reactivity originally observed. Based on our observations we suggest that the IgE reactive 12kDa protein from almond currently known as Pru du 2S albumin is in reality the cleaved N-terminal region of a 7S vicilin like protein. PMID:25854802

  17. The interaction between bovine serum albumin and surfactants.

    PubMed Central

    Jones, M N; Skinner, H A; Tipping, E

    1975-01-01

    1. Potassium n-decyl phosphate binds exothermically to bovine serum albumin at pH 7.0 to form a specific complex containing approx. 60 phosphate anions. 2. The formation of the complex is accompanied by changes in the u.v. difference spectrum of the protein. 3. At higher phosphate concentrations (above 0.4mM) surfactant molecules continue to be bound, and the protein undergoes a gross change in conformation. 4. n-Dodecyltri-methylammonium bromide binds endothermically to bovine serum albumin at pH7.0 but the extent of binding for a given free surfactant concentration is less than for the phosphate surfactant. 5. Binding is accompanied by a small change in the specific viscosity and by changes in the u.v. difference spectrum of the protein. 6. It is suggested that over the surfactant concentration ranges studied n-decyl phosphate ions first bind to the C-terminal part of the protein and then to the more compact N-terminal part whereas n-dodecyltrimethylammonium ions bind only to the C-terminal part of bovine serum albumin. PMID:1180891

  18. Effect of tribology processes on adsorption of albumin

    NASA Astrophysics Data System (ADS)

    Yan, Yu; Yang, Hongjuan; Wang, Linghe; Su, Yanjing; Qiao, Lijie

    2016-03-01

    As soon as artificial joint replacements are implanted into patients, the adsorption of proteins can occur. Joint implants operate in a protein-rich and relatively corrosive environment under tribological contact. The contacted area acted as an anodic part and the rest of the surface was more cathodic. Therefore, the adsorption of proteins is different in and outside the wear track. Adsorbed proteins would denature during rubbing and a tribofilm could form. The tribofilm can lubricate the surface and act as a barrier to corrosion damage. However, to observe the adsorption of proteins in situ has always been a challenge. Scanning Kelvin probe force microscope (SKPFM) was used to study the adsorption of albumin on the surface of CoCrMo alloy under simulated tribology movement. Fluorescence microscopy (FM) was employed to reveal the protein molecules in the wear scar. It was found that albumin molecules can decrease the surface potential and accelerate the corrosion process. In the wear track, albumin denatured and changed the surface potential as time progressed.

  19. Study on dioxygen reduction by mutational modifications of the hydrogen bond network leading from bulk water to the trinuclear copper center in bilirubin oxidase

    SciTech Connect

    Morishita, Hirotoshi; Kurita, Daisuke; Kataoka, Kunishige; Sakurai, Takeshi

    2014-07-18

    Highlights: • Proton transport pathway in bilirubin oxidase was mutated. • Two intermediates in the dioxygen reduction steps were trapped and characterized. • A specific glutamate for dioxygen reduction by multicopper oxidases was identified. - Abstract: The hydrogen bond network leading from bulk water to the trinuclear copper center in bilirubin oxidase is constructed with Glu463 and water molecules to transport protons for the four-electron reduction of dioxygen. Substitutions of Glu463 with Gln or Ala were attributed to virtually complete loss or significant reduction in enzymatic activities due to an inhibition of the proton transfer steps to dioxygen. The single turnover reaction of the Glu463Gln mutant afforded the highly magnetically interacted intermediate II (native intermediate) with a broad g = 1.96 electron paramagnetic resonance signal detectable at cryogenic temperatures. Reactions of the double mutants, Cys457Ser/Glu463Gln and Cys457Ser/Glu463Ala afforded the intermediate I (peroxide intermediate) because the type I copper center to donate the fourth electron to dioxygen was vacant in addition to the interference of proton transport due to the mutation at Glu463. The intermediate I gave no electron paramagnetic resonance signal, but the type II copper signal became detectable with the decay of the intermediate I. Structural and functional similarities between multicopper oxidases are discussed based on the present mutation at Glu463 in bilirubin oxidase.

  20. The impact of oxidized serum albumin on the oncotic pressure and hydration status of peritoneal dialysis patients

    PubMed Central

    Hassan, Kamal; Kristal, Batya; Hassan, Fadi; Abo Saleh, Saad; Michelis, Regina

    2016-01-01

    Objective Hypoalbuminemia, fluid overload (FO), and oxidative stress (OS) may be related to cardiovascular morbidity and mortality in peritoneal dialysis (PD) patients. OS produces molecular modifications of serum albumin that interfere with its quantification by the commonly used bromocresol green assay. This study evaluated the impact of oxidized serum albumin (OSA) on oncotic pressure (OP) and hydration status. Patients and methods Twenty-four stable hypoalbuminemic PD patients were enrolled in the study. After performing physical examination, assessment of the hydration status using a whole-body bioimpedance spectroscopy technique was performed, and blood samples were drawn for determination of OP, serum albumin levels, and OSA. Results Extracellular to total body water (E/TBW) ratio was higher in patients with FO ≥1.5 L with or without edema than in patients with FO <1.5 L (P≤0.043). E/TBW ratio was higher in patients with FO ≥1.5 L and edema compared to those with FO ≥1.5 L but without edema (P=0.004). OP was significantly higher in patients with FO ≥1.5 L and without edema compared to those with FO ≥1.5 L and with edema (P<0.001). Albumin-detection index (ADI) in patients with FO ≥1.5 L and without edema was similar to ADI in patients with FO <1.5 L (P=0.520). ADI was significantly lower in patients with FO ≥1.5 L and without edema compared to those with FO ≥1.5 L and edema (P=0.034). E/TBW ratio correlated positively with the ADI (r=0.60, P=0.001) and inversely with the OP (r=−0.54, P=0.002). Conclusion Overhydration may be clinically undetectable in PD patients. Assessing the hydration status and measuring the total serum albumin levels, including the oxidized fraction, should be considered in evaluating hydration status in PD patients. PMID:27069365

  1. Glycated serum albumin: a potential disease marker and an intermediate index of diabetes control.

    PubMed

    Raghav, Alok; Ahmad, Jamal

    2014-01-01

    Glycation is a non-enzymatic spontaneous process in proteins which has remarkable impact on its physical and functional aspect. This alteration with addition of carbohydrate residue to human serum albumin leads to several pathological events such as diabetic nephropathy, neuropathy, retinopathy and cardiovascular complications. Human serum albumin is the major protein and is most susceptible to non-enzymatic glycation. Structural and biological properties of functional albumin alter due to the addition of reducing carbohydrate to free amino terminal residues vivo. These irreversible changes in functional albumin are stable which makes this modified albumin as new gold standard future diagnostic marker in diabetes associated complications. Glycated albumin can be used to determine the glycemic control due to short half life than erythrocytes which makes it an alternate reliable disease marker in diabetes. In this review, Human serum albumin glycation has been overviewed, stating concept of glycation and sites that are prone to this modifications. Impact of non-enzymatic addition of carbohydrate to albumin's structural and biological properties has also been elaborated. Accurate measurements of glycated albumin with implications of new highly sensitive techniques have also been described briefly. Interestingly human serum albumin imposed glycation can serve as future tool not for diagnosing diabetes but also its potential in assessment of diabetes associated complications. PMID:25311816

  2. The relationship between serum albumin levels and 24-h ambulatory blood pressure monitoring recordings in non-diabetic essential hypertensive patients

    PubMed Central

    Ahbap, Elbis; Sakaci, Tamer; Kara, Ekrem; Sahutoglu, Tuncay; Koc, Yener; Basturk, Taner; Sevinc, Mustafa; Akgol, Cuneyt; Kayalar, Arzu O.; Ucar, Zuhal A.; Bayraktar, Feyza; Unsal, Abdulkadir

    2016-01-01

    OBJECTIVES: The goal of this study was to evaluate the relationship between serum albumin levels and 24-hour ambulatory blood pressure monitoring (24-h ABPM) recordings in non-diabetic essential hypertensive patients. METHODS: A total of 354 patients (mean [SD] age: 55.5 [14.3] years, 50% females) with essential hypertension and 24-h ABPM recordings were included. Patient 24-h nighttime and daytime ABPM values, systolic and diastolic dipping status and average nocturnal dipping were recorded. The correlations between serum albumin levels and nocturnal systolic and diastolic dipping were evaluated, and correlates of average nocturnal systolic dipping were determined via a linear regression model. RESULTS: Overall, 73.2% of patients were determined to be non-dippers. The mean (SD) levels of serum albumin (4.2 [0.3] g/dL vs. 4.4 [0.4] g/dL, p<0.001) and the average nocturnal systolic (15.2 [4.8] mmHg vs. 0.3 [6.6] mmHg, p<0.001) and diastolic dipping (4.2 [8.6] mmHgvs. 18.9 [7.0] mmHg, p<0.001) were significantly lower in non-dippers than in dippers. A significant positive correlation was noted between serum albumin levels and both systolic (r=0.297, p<0.001) and diastolic dipping (r=0.265, p<0.001). The linear regression analysis revealed that for each one-unit increase in serum albumin, the average nocturnal dip in systolic BP increased by 0.17 mmHg (p=0.033). CONCLUSION: Our findings indicate an association between serum albumin levels and the deterioration of circadian BP rhythm among essential hypertensive patients along with the identification of a non-dipper pattern in more than two-thirds of patients. Our findings emphasize the importance of serum albumin levels, rather than urinary albumin excretion, as an independent predictor of nocturnal systolic dipping, at least in non-diabetic essential hypertensive patients with moderate proteinuria. PMID:27276394

  3. Novel Transgenic Mouse Model for Studying Human Serum Albumin as a Biomarker of Carcinogenic Exposure.

    PubMed

    Sheng, Jonathan; Wang, Yi; Turesky, Robert J; Kluetzman, Kerri; Zhang, Qing-Yu; Ding, Xinxin

    2016-05-16

    Albumin is a commonly used serum protein for studying human exposure to xenobiotic compounds, including therapeutics and environmental pollutants. Often, the reactivity of albumin with xenobiotic compounds is studied ex vivo with human albumin or plasma/serum samples. Some studies have characterized the reactivity of albumin with chemicals in rodent models; however, differences between the orthologous peptide sequences of human and rodent albumins can result in the formation of different types of chemical-protein adducts with different interaction sites or peptide sequences. Our goal is to generate a human albumin transgenic mouse model that can be used to establish human protein biomarkers of exposure to hazardous xenobiotics for human risk assessment via animal studies. We have developed a human albumin transgenic mouse model and characterized the genotype and phenotype of the transgenic mice. The presence of the human albumin gene in the genome of the model mouse was confirmed by genomic PCR analysis, whereas liver-specific expression of the transgenic human albumin mRNA was validated by RT-PCR analysis. Further immunoblot and mass spectrometry analyses indicated that the transgenic human albumin protein is a full-length, mature protein, which is less abundant than the endogenous mouse albumin that coexists in the serum of the transgenic mouse. The transgenic protein was able to form ex vivo adducts with a genotoxic metabolite of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, a procarcinogenic heterocyclic aromatic amine formed in cooked meat. This novel human albumin transgenic mouse model will facilitate the development and validation of albumin-carcinogen adducts as biomarkers of xenobiotic exposure and/or toxicity in humans. PMID:27028147

  4. The transport of albumin across the ferret in vitro whole trachea.

    PubMed Central

    Webber, S E; Widdicombe, J G

    1989-01-01

    1. The whole trachea of the ferret has been isolated in vitro in an organ bath and used to study the transport of bovine serum albumin (BSA) and two dextrans (70,000 and 9000 Da) from external buffer solution to air-filled lumen, assessed by fluorescent-labelled tracers. 2. In control conditions, when mucus secretion was not stimulated by drugs, the concentration of albumin in the lumen was over half that in the buffer, and about six times greater than those of the two dextrans. 3. Methacholine and phenylephrine caused large increases in mucus secretion and albumin output and decreases in albumin concentration. The responses were proportional to drug concentration. We concluded that albumin output is increased but diluted with submucosal gland secretion. 4. Salbutamol caused a small increase in mucus secretion and large increases in output and concentration of albumin. The concentration of albumin became greater than that in the external buffer medium. The responses were proportional to concentration of salbutamol. 5. Histamine increased mucus secretion and albumin output and concentration. 6. None of the four drugs increased the output of dextran-70,000. Methacholine and phenylephrine increased the output of dextran-9000, but to a far less extent than for albumin. 7. Cooling the trachea and buffer to 4 degrees C almost abolished the stimulation of mucus and albumin outputs due to methacholine. 8. Increasing the concentration of albumin external to the trachea did not proportionally increase albumin secretion, the logarithmic relationship suggesting saturation of an active transport system. 9. We conclude that albumin is secreted by active transport into the tracheal lumen, and that the rate of transport can be augmented by salbutamol to build up a higher concentration in the lumen than in the external buffer. Images Fig. 7 PMID:2476558

  5. Cellular Specificity of the Blood–CSF Barrier for Albumin Transfer across the Choroid Plexus Epithelium

    PubMed Central

    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

  6. 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

  7. Role of Serum Interleukin 6, Albumin and C-Reactive Protein in COPD Patients

    PubMed Central

    Emami Ardestani, Mohammad

    2015-01-01

    Background: Chronic obstructive pulmonary disease (COPD) is a non-specific inflammation, which involves the airways, lung parenchyma and pulmonary vessels. The inflammation causes the activation of inflammatory cells and the release of various inflammatory mediators such as interleukin-8 (IL-8), IL-6 and tumor necoris factor alpha (TNF-a). The purpose of the present study was to measure serum IL-6, C-reactive protein (CRP) (as a positive phase reactant) and albumin level (as a negative phase reactant) in COPD patients (only due to cigarette smoking not bio-mass), non COPD smokers and healthy subjects using enzyme-linked immunosorbent assay (ELISA); we compared the differences in inflammatory factors among groups. Materials and Methods: A total of 180 males were enrolled in this study and divided into three equal groups. The first group was 60 smokers who had COPD. The second group included 60 smokers without COPD and the third group consisted of people who were not smokers and did not have COPD; 5 mL of venous blood was taken from all participants and it was collected in a test tube containing anticoagulant and then centrifuged at 3000 rpm for 10 minutes. Serum was separated and used to measure the amount of IL-6, CRP and albumin. Spirometry was performed according to the criteria set by the American Thoracic Society. Results: The mean serum level of IL-6 was 83.2±7.5 pg/mL in group I, 54.9±24.3 pg/mL in group II and 46.9±10.4 pg/mL in group III. There was a significant difference among the three groups (P<0.001). The mean serum level of CRP was 28.9±14.9 mg/dL in the first group, 19.9±8.5 mg/dL in the second group and 4.2±2.3 mg/dL in the third group (P=0.02). But by controlling the confounding effects of age, this difference was not significant (P=0.49). The mean serum level of albumin was I 4.1±0.57 mg/dL in group I, 4.3±0.56 mg/dL in group II and 4.1±0.53 mg/dL in group III. There was no significant difference among the three groups in this regard (P=0

  8. Influence of Phosphatidylcholine and Calcium on Self-Association and Bile Salt Mixed Micellar Binding of the Natural Bile Pigment, Bilirubin Ditaurate.

    PubMed

    Neubrand, Michael W; Carey, Martin C; Laue, Thomas M

    2015-11-17

    Recently [Neubrand, M. W., et al. (2015) Biochemistry 54, 1542-1557], we determined a concentration-dependent monomer-dimer-tetramer equilibrium in aqueous bilirubin ditaurate (BDT) solutions and explored the nature of high-affinity binding of BDT monomers with monomers and micelles of the common taurine-conjugated bile salts (BS). We now investigate, employing complementary physicochemical methods, including fluorescence emission spectrophotometry and quasi-elastic light scattering spectroscopy, the influence of phosphatidylcholine (PC), the predominant phospholipid of bile and calcium, the major divalent biliary cation, on these self-interactions and heterointeractions. We have used short-chain, lyso and long-chain PC species as models and contrasted our results with those of parallel studies employing unconjugated bilirubin (UCB) as the fully charged dianion. Both bile pigments interacted with the zwitterionic headgroup of short-chain lecithins, forming water-soluble (BDT) and insoluble ion-pair complexes (UCB), respectively. Upon micelle formation, BDT monomers apparently remained at the headgroup mantle of short-chain PCs, but the ion pairs with UCB became internalized within the micelle's hydrophobic core. BDT interacted with the headgroups of unilamellar egg yolk (EY) PC vesicles; however, with the simultaneous addition of CaCl2, a reversible aggregation took place, but not vesicle fusion. With mixed EYPC/BS micelles, BDT became bound to the hydrophilic surface (as with simple BS micelles), and in turn, both BDT and BS bound calcium, but not other divalent cations. The calcium complexation of BDT and BS was enhanced strongly with increases in micellar EYPC, suggesting calcium-mediated cross-bridging of hydrophilic headgroups at the micelle's surface. Therefore, the physicochemical binding of BDT to BS in an artificial bile medium is influenced not only by BS species and concentration but also by long-chain PCs and calcium ions that exert a specific rather

  9. Bilirubin UDP-Glucuronosyltransferase 1A1 (UGT1A1) Gene Promoter Polymorphisms and HPRT, Glycophorin A, and Micronuclei Mutant Frequencies in Human Blood

    SciTech Connect

    Grant, D; Hall, I J; Eastmond, D; Jones, I M; Bell, D A

    2004-10-06

    A dinucleotide repeat polymorphism (5-, 6-, 7-, or 8-TA units) has been identified within the promoter region of UDP-glucuronosyltransferase 1A1 gene (UGT1A1). The 7-TA repeat allele has been associated with elevated serum bilirubin levels that cause a mild hyperbilirubinemia (Gilbert's syndrome). Studies suggest that promoter transcriptional activity of UGT1A1 is inversely related to the number of TA repeats and that unconjugated bilirubin concentration increases directly with the number of TA repeat elements. Because bilirubin is a known antioxidant, we hypothesized that UGT1A1 repeats associated with higher bilirubin may be protective against oxidative damage. We examined the effect of UGT1A1 genotype on somatic mutant frequency in the hypoxanthine-guanine phosphoribosyl-transferase (HPRT) gene in human lymphocytes and the glycophorin A (GPA) gene of red blood cells (both N0, NN mutants), and the frequency of lymphocyte micronuclei (both kinetochore (K) positive or micronuclei K negative) in 101 healthy smoking and nonsmoking individuals. As hypothesized, genotypes containing 7-TA and 8-TA displayed marginally lower GPA{_}NN mutant frequency relative to 5/5, 5/6, 6/6 genotypes (p<0.05). In contrast, our analysis showed that lower expressing UGT1A1 alleles (7-TA and 8-TA) were associated with modestly increased HPRT mutation frequency (p<0.05) while the same low expression genotypes were not significantly associated with micronuclei frequencies (K-positive or K-negative) when compared to high expression genotypes (5-TA and 6-TA). We found weak evidence that UGT1A1 genotypes containing 7-TA and 8-TA were associated with increased GPA{_}N0 mutant frequency relative to 5/5, 5/6, 6/6 genotypes (p<0.05). These data suggest that UGT1A1 genotype may modulate somatic mutation of some types, in some cell lineages, by a mechanism not involving bilirubin antioxidant activity. More detailed studies examining UGT1A1 promoter variation, oxidant/antioxidant balance and genetic

  10. Inhibitory effect of gold nanoparticles on the D-ribose glycation of bovine serum albumin

    PubMed Central

    Liu, Weixi; Cohenford, Menashi A; Frost, Leslie; Seneviratne, Champika; Dain, Joel A

    2014-01-01

    Formation of advanced glycation end products (AGEs) by nonenzymatic glycation of proteins is a major contributory factor to the pathophysiology of diabetic conditions including senile dementia and atherosclerosis. This study describes the inhibitory effect of gold nanoparticles (GNPs) on the D-ribose glycation of bovine serum albumin (BSA). A combination of analytical methods including ultraviolet–visible spectrometry, high performance liquid chromatography, circular dichroism, and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry were used to determine the extent of BSA glycation in the presence of citrate reduced spherical GNPs of various sizes and concentrations. GNPs of particle diameters ranging from 2 nm to 20 nm inhibited BSA’s AGE formation. The extent of inhibition correlated with the total surface area of the nanoparticles. GNPs of highest total surface area yielded the most inhibition whereas those with the lowest total surface area inhibited the formation of AGEs the least. Additionally, when GNPs’ total surface areas were set the same, their antiglycation activities were similar. This inhibitory effect of GNPs on BSA’s glycation by D-ribose suggests that colloidal particles may have a therapeutic application for the treatment of diabetes and conditions that promote hyperglycemia. PMID:25473284

  11. Hydrophilic bile acids protect human blood-brain barrier endothelial cells from disruption by unconjugated bilirubin: an in vitro study

    PubMed Central

    Palmela, Inês; Correia, Leonor; Silva, Rui F. M.; Sasaki, Hiroyuki; Kim, Kwang S.; Brites, Dora; Brito, Maria A.

    2015-01-01

    Ursodeoxycholic acid and its main conjugate glycoursodeoxycholic acid are bile acids with neuroprotective properties. Our previous studies demonstrated their anti-apoptotic, anti-inflammatory, and antioxidant properties in neural cells exposed to elevated levels of unconjugated bilirubin (UCB) as in severe jaundice. In a simplified model of the blood-brain barrier, formed by confluent monolayers of a cell line of human brain microvascular endothelial cells, UCB has shown to induce caspase-3 activation and cell death, as well as interleukin-6 release and a loss of blood-brain barrier integrity. Here, we tested the preventive and restorative effects of these bile acids regarding the disruption of blood-brain barrier properties by UCB in in vitro conditions mimicking severe neonatal hyperbilirubinemia and using the same experimental blood-brain barrier model. Both bile acids reduced the apoptotic cell death induced by UCB, but only glycoursodeoxycholic acid significantly counteracted caspase-3 activation. Bile acids also prevented the upregulation of interleukin-6 mRNA, whereas only ursodeoxycholic acid abrogated cytokine release. Regarding barrier integrity, only ursodeoxycholic acid abrogated UCB-induced barrier permeability. Better protective effects were obtained by bile acid pre-treatment, but a strong efficacy was still observed by their addition after UCB treatment. Finally, both bile acids showed ability to cross confluent monolayers of human brain microvascular endothelial cells in a time-dependent manner. Collectively, data disclose a therapeutic time-window for preventive and restorative effects of ursodeoxycholic acid and glycoursodeoxycholic acid against UCB-induced blood-brain barrier disruption and damage to human brain microvascular endothelial cells. PMID:25821432

  12. Anti-cancer effects of blue-green alga Spirulina platensis, a natural source of bilirubin-like tetrapyrrolic compounds.

    PubMed

    Koníčková, Renata; Vaňková, Kateřina; Vaníková, Jana; Váňová, Kateřina; Muchová, Lucie; Subhanová, Iva; Zadinová, Marie; Zelenka, Jaroslav; Dvořák, Aleš; Kolář, Michal; Strnad, Hynek; Rimpelová, Silvie; Ruml, Tomáš; J Wong, Ronald; Vítek, Libor

    2014-01-01

    Spirulina platensis is a blue-green alga used as a dietary supplement because of its hypocholesterolemic properties. Amo