The synthesis of 13C-bilirubin and its use in the validation of bilirubin kinetic studies in rats

International Nuclear Information System (INIS)

Sturrock, E.D.

1994-04-01

The total synthesis of [10- 13 C] bilirubin IXα], the principal waste product of haem degradation, is described. Site specific labelling was accomplished by the Vilsmeier formulation of one of the dipyrrolic fragments using [1- 13 C] dimethylformamide. The penultimate dehydrohalogenation reaction was complicated by a competing elimination reaction which yielded a bridged biliverdin derivative. The base catalysed reaction affords a novel [10- 13 C]-8,12-bis(2-methoxycarbonylethyl)-7,13,17-trimethyl-2,18-propano-3-vinylbilin-1,19(21H,24H)-dione in which the 2 and 18 positions of the macrocycle are bridged with a propano tether, the structure has been established using single crystal X-ray and 1 H nuclear Overhauser effect studies. [ 14 C]bilirubin was prepared, bio synthetically, using [ 14 C]aminolevulinic acid. Bilirubin kinetics in 4 rats were measured by the analysis of the plasma disappearance of [ 14 C]bilirubin in a two-compartment model. The plasma half-life of the first and second exponentials were 1.97 and 32.8 minutes respectively. The data were used to determine model independent parameters k 12 , k 21 , and k 20 . In the proposed model, plasma unconjugated bilirubin exchanges with a hepatic unconjugated bilirubin pool. Bilirubin is eliminated from the system via the proposed hepatic pool. These studies provide an analysis of the kinetics of unconjugated bilirubin in rates and are intended to serve as a reference point for studies using a stable isotope of bilirubin. The plasma disappearance of [10- 13 C]bilirubin IXα in three rats was studied using mass spectrometry to measure the bilirubin δ 13 C. Validation of the experimental procedure in terms of range and reproducibility of the detection method was carried out. The half lives of the initial and terminal exponentials were 2.27±2.5 and 22.8±12.9 minutes. Despite the large 95% confidence limits calculated for these clearance curves they serve as an important foundation for future bilirubin kinetic

Studies on bile acid and bilirubin in liver diseases Part 2. Clinical significance of serum bilirubin sulfate in various liver diseases

OpenAIRE

石川, 泰祐

1980-01-01

The clinical significance of serum bilirubin sulfate, one of the direct bilirubin, was evaluated in various liver diseases with over 2 mg/dl of serum bilirubin concentration. The diagnosis included 25 cases of acute hepatitis, 8 cases of chronic hepatitis, 8 cases of liver cirrhosis and 16 cases of liver cirrhosis with hepatoma. Bilirubin sulfate was fractioned by Yonei's solvent partition method. The clinical significance of bilirubin sulfate was assessed by comparison of bilirubin sulfate w...

Bilirubin-Induced Neurotoxicity in the Preterm Neonate.

Science.gov (United States)

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. Copyright © 2016 Elsevier Inc. All rights reserved.

Serum Bilirubin Concentrations in Patients With Takayasu Arteritis.

Science.gov (United States)

Peng, You-Fan; Deng, Yi-Bin

2017-06-01

- Bilirubin has strong anti-inflammatory and antioxidative stress action. Progression of inflammation involving arteries is a crucial activator in pathogenesis of Takayasu arteritis (TA). - To investigate the relationship between serum bilirubin and TA. - Our study involved 115 consecutive TA patients. Patients with active-phase disease were followed and received prednisone therapy. - Lower concentrations of serum bilirubin were detected in TA patients compared with healthy subjects (0.6 ± 0.31 versus 0.7 ± 0.22 mg/dL, P = .02). Serum bilirubin concentrations in active TA patients were lower than those in inactive patients (0.5 ± 0.20 versus 0.8 ± 0.32 mg/dL, P bilirubin correlated positively with total protein (r = 0.193, P = .04) and negatively with C-reactive protein and erythrocyte sedimentation rate (r = -0.213, P = .03, and r = -0.532, P bilirubin was associated with a 1.10 times increase in the odds for TA compared with the controls (odds ratio = 0.913, 95% CI, 0.856-0.974; P = .006). Serum bilirubin was correlated with erythrocyte sedimentation rate (β = -0.170, P bilirubin in predicting active TA patients was 0.802. Serum bilirubin levels were found to be significantly increased after prednisone treatment (0.5 ± 0.20 versus 0.7 ± 0.15 mg/dL, P = .002). - Lower serum bilirubin levels are associated with TA, and serum bilirubin may be influenced by prednisone therapy in active TA patients. Serum bilirubin levels in TA patients correlate negatively with erythrocyte sedimentation rate.

Functionalized SBA-15 materials for bilirubin adsorption

Science.gov (United States)

Tang, Tao; Zhao, Yanling; Xu, Yao; Wu, Dong; Xu, Jun; Deng, Feng

2011-05-01

To investigate the driving force for bilirubin adsorption on mesoporous materials, a comparative study was carried out between pure siliceous SBA-15 and three functionalized SBA-15 mesoporous materials: CH 3-SBA-15 (MS), NH 2-SBA-15 (AS), and CH 3/NH 2-SBA-15 (AMS) that were synthesized by one-pot method. The obtained materials exhibited large surface areas (553-810 m 2/g) and pore size (6.6-7.1 nm) demonstrated by XRD and N 2-ad/desorption analysis. The SEM images showed that the materials had similar fiberlike morphology. The functionalization extent was calculated according to 29Si MAS NMR spectra and it was close to the designed value (10%). The synthesized mesoporous materials were used as bilirubin adsorbents and showed higher bilirubin adsorption capacities than the commercial active carbon. The adsorption capacities of amine functionalized samples AMS and AS were larger than those of pure siliceous SBA-15 and MS, indicating that electrostatic interaction was the dominant driving force for bilirubin adsorption on mesoporous materials. Increasing the ionic strength of bilirubin solution by adding NaCl would decrease the bilirubin adsorption capacity of mesoporous material, which further demonstrated that the electrostatic interaction was the dominant driving force for bilirubin adsorption. In addition, the hydrophobic interaction provided by methyl groups could promote the bilirubin adsorption.

The effect of gamma-radiation on bilirubin

International Nuclear Information System (INIS)

Iqbal, M.S.; Shad, M.A.; Akhtar, M.I.

2001-01-01

The effect of gamma-radiations on bilirubin, in vitro, has been studied. It was found that gamma-radiation causes oxidation of bilirubin to biliverdine as one of the products. The likely implication of this effect in transformation of bilirubin to excretable products, in vino, in case of jaundice is discussed. (author)

Hepatic conversion of bilirubin monoglucuronide to diglucuronide in uridine diphosphate-glucuronyl transferase-deficient man and rat by bilirubin glucuronoside glucuronosyltransferase

NARCIS (Netherlands)

Chowdhury, J. R.; Jansen, P. L.; 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

Does bilirubin protect against developing diabetes mellitus?

Science.gov (United States)

Breimer, Lars H; Mikhailidis, Dimitri P

2016-01-01

After 25 years of evaluating bilirubin as a possible protective agent in neonatal and cardiovascular disease, interest has moved on to a exploring a possible protective role in diabetes mellitus (DM). This review finds conflicting prospective data for a protective relationship though there are retrospective, case-controlled data, that can only show association, which is not causality. Only prospective studies can show causality. Also, it would appear that the underlying biochemical assumptions do not readily translate from the animal to the human setting. Given that many factors impact on circulating bilirubin levels, it is not surprising that a clear-cut answer is not available; the jury is still out. Any relationship between DM and bilirubin might relate to intermediates in bilirubin metabolism, including relationships involving the genes for the enzymes participating in those steps. Nevertheless, the pursuit of bilirubin in disease causation is opening new avenues for research and if it is established that serum bilirubin can predict risks, much will have been achieved. The answer may have to come from molecular genetic analyses. Copyright © 2016 Elsevier Inc. All rights reserved.

Bilirubin bound to cells does not form photoisomers

International Nuclear Information System (INIS)

Christensen, T.; Kinn, G.

1993-01-01

Cultured cells from one human and one murine cell line were incubated with bilirubin by different methods that allowed bilirubin to be bound to cells. The cells were irradiated with visible light of different wavelengths. Bilirubin bound to human serum albumin was also irradiated with light. After irradiation, bilirubin and its photoisomers were extracted and analyzed by HPLC. No photoisomers were found in samples of irradiated cells, while the types and amounts of photoisomers that were expected from the literature were found in samples of irradiated bilirubin/albumin mixtures. It is concluded that the formation of therapeutically active photoisomers during phototherapy most probably does not take place in skin cells, but most likely in bilirubin bound to albumin in the vessels or in the interstitial space. 16 refs., 2 figs

Bilirubin Blood Test: MedlinePlus Lab Test Information

Science.gov (United States)

... this page: https://medlineplus.gov/labtests/bilirubinbloodtest.html Bilirubin Blood Test To use the sharing features on this page, please enable JavaScript. What is a Bilirubin Blood Test? A bilirubin blood test measures the ...

The triplet excited state of bilirubin

International Nuclear Information System (INIS)

Land, E.J.

1976-01-01

Pulse radiolysis of benzene solutions of 40 μM bilirubin alone or with 0.1 M biphenyl has yielded evidence for the formation of the triplet excited state of bilirubin. Measurements were made of a number of properties, including the absorption spectrum (lambdasub(max)500nm), lifetime 9μs), extinction coefficient (8800 M -1 cm -1 ), energy level (approximately 150 kJ mol -1 ) and the rate of quenching by oxygen (rate constant, 8.2 x 10 8 M -1 s -1 ). An upper limit of 0.1 has also been obtained for the singlet to triplet crossover efficiency of bilirubin following excitation by 353 nm radiation. Consideration is given to the relevance of these data to the mechanism of bilirubin photo-destruction, both in vivo and in vitro. (U.K.)

Towards bilirubin imprinted poly(methacrylic acid-co-ethylene glycol dimethylacrylate) for the specific binding of α-bilirubin

International Nuclear Information System (INIS)

Syu, M.-J.; Deng, J.-H.; Nian, Y.-M.

2004-01-01

With α-bilirubin as a molecular template, polymerization of methacrylic acid (MAA) was carried out with the aid of the initiator 2,2-azobisisobutyronitrile (AIBN) and the cross-linking agent ethylene glycol dimethylacrylate (EGDMA). Bulk polymerization was successfully carried out so that poly(methacrylic acid-co-ethylene glycol dimethylacrylate) (poly(MAA-EGDMA)) imprinted with α-bilirubin was first developed. UV irradiation polymerization and heated polymerization methods were compared. Effect of different ratios of monomer to EGDMA during the polymerization was also discussed. Proper solvent for better desorption of α-bilirubin from the imprinted poly(MAA-EGDMA) was investigated. In addition, SEM photos were provided for observing the differences between the surfaces of the imprinted poly(MAA-EGDMA) before and after extraction. The corresponding binding results of α-bilirubin imprinted poly(MAA-EGDMA) and non-imprinted poly(MAA-EGDMA) both after extraction were compared. How the pH values during extraction stage affected the binding capacities of the imprinted polymer as well as non-imprinted polymer were also discussed. Similar study and comparison were made for different binding pH values. Different compounds of similar molecular weight were used to show the specific binding of the imprinted polymer for bilirubin. The results further confirmed the successful binding as well as specificity of the imprinted poly(MAA-EGDMA) for α-bilirubin

Serum bilirubin and the risk of rheumatoid arthritis.

Science.gov (United States)

Juping, Du; Yuan, Yuan; Shiyong, Chen; Jun, Li; Xiuxiu, Zhou; Haijian, Ying; Jianfeng, Shi; Bo, Shen

2017-11-01

Oxidative stress and immune imbalance play an important role in the pathogenesis of rheumatoid arthritis (RA). Bilirubin is a powerful antioxidant and also regarded as immunomodulator. Increased evidence shows that bilirubin should be a protective factor for autoimmune disease. However, the relationship between bilirubin and RA remain unclear. We analyzed serum bilirubin levels and other laboratory and clinical data in 130 RA patients (35 patients without any complications), 81 osteoarthritis (OA) patients and 96 healthy controls. Binary logistic regression adjusted by age and gender revealed that the levels of serum total, indirect bilirubin were significantly lower in RA patients, when compared with healthy controls (P=.015, OR=0.767, 95% CI=0.619-0.951; P=.010, OR=0.664, 95% CI=0.487-0.906, respectively) or OA patients (P=.000, OR=0.763, 95% CI=0.661-0.882; P=.000, OR=0.656, 95% CI=0.532-0.808, respectively). A reduced trend of levels of bilirubin has been detected along with increased disease activity, despite with no significance (P>.05). Spearman rank test further demonstrated that IgG and ESR were negative associated with total, indirect bilirubin, and albumin, prealbumin, APOA, HDL-C were positively associated with bilirubin. In conclusion, the levels of serum bilirubins were decreased in RA, and decreased levels could be associated with IgG, albumin and inflammatory marker ESR. © 2017 Wiley Periodicals, Inc.

Animal pigment bilirubin discovered in plants.

Science.gov (United States)

Pirone, Cary; Quirke, J Martin E; Priestap, Horacio A; Lee, David W

2009-03-04

The bile pigment bilirubin-IXalpha is the degradative product of heme, distributed among mammals and some other vertebrates. It can be recognized as the pigment responsible for the yellow color of jaundice and healing bruises. In this paper we present the first example of the isolation of bilirubin in plants. The compound was isolated from the brilliant orange-colored arils of Strelitzia nicolai, the white bird of paradise tree, and characterized by HPLC-ESMS, UV-visible, (1)H NMR, and (13)C NMR spectroscopy, as well as comparison with an authentic standard. This discovery indicates that plant cyclic tetrapyrroles may undergo degradation by a previously unknown pathway. Preliminary analyses of related plants, including S. reginae, the bird of paradise, also revealed bilirubin in the arils and flowers, indicating that the occurrence of bilirubin is not limited to a single species or tissue type.

Supramolecular Complexes Formed in Systems Bile Salt-Bilirubin-Silica

Science.gov (United States)

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

The formation of supramolecular complexes between bilirubin and primary micelles of bile salts has been studied. The association constants of bile salts and binding of bilirubin with these associates have been determined. The adsorption of bilirubin and bile salts from individual and mixed aqueous solutions onto hydrophobic silica surfaces has been investigated. The interaction of bilirubin with primary bile salt micelles and the strong retention in mixed micelles, which are supramolecular complexes, result in the adsorption of bilirubin in free state only.

Stopped-flow studies of spectral changes in bilirubin-human serum albumin following an alkaline pH jump and following binding of bilirubin

DEFF Research Database (Denmark)

Honoré, B

1987-01-01

A stopped-flow technique was used to study the spectral changes occurring in bilirubin-albumin following a pH jump as well as following binding of bilirubin at 25 degrees C. The changes were studied in two wavelength ranges, 280-310 nm (tyrosine residues) and 400-510 nm (bound bilirubin). The cha......A stopped-flow technique was used to study the spectral changes occurring in bilirubin-albumin following a pH jump as well as following binding of bilirubin at 25 degrees C. The changes were studied in two wavelength ranges, 280-310 nm (tyrosine residues) and 400-510 nm (bound bilirubin......). The changes were analyzed according to a scheme of consecutive unimolecular reactions. Spectral monitoring of a pH jump from 11.3 to 11.8 reveals that the bilirubin-albumin complex changes its structure in several steps. The UV absorption spectra show that 3.8 tyrosine residues ionize in the first step, 2...

The Bilirubin Binding Panel: A Henderson-Hasselbalch Approach to Neonatal Hyperbilirubinemia.

Science.gov (United States)

Ahlfors, Charles E

2016-10-01

Poor plasma bilirubin binding increases the risk of bilirubin neurotoxicity in newborns with hyperbilirubinemia. New laboratory tests may soon make it possible to obtain a complete bilirubin binding panel when evaluating these babies. The 3 measured components of the panel are the plasma total bilirubin concentration (B Total ), which is currently used to guide clinical care; the bilirubin binding capacity (BBC); and the concentration of non-albumin bound or free bilirubin (B Free ). The fourth component is the bilirubin-albumin equilibrium dissociation constant, K D , which is calculated from B Total , BBC, and B Free The bilirubin binding panel is comparable to the panel of components used in the Henderson-Hasselbalch approach to acid-base assessment. Bilirubin binding population parameters (not prospective studies to determine whether the new bilirubin binding panel components are better predictors of bilirubin neurotoxicity than B Total ) are needed to expedite the clinical use of bilirubin binding. At any B Total , the B Free and the relative risk of bilirubin neurotoxicity increase as the K D /BBC ratio increases (ie, bilirubin binding worsens). Comparing the K D /BBC ratio of newborns with B Total of concern with that typical for the population helps determine whether the risk of bilirubin neurotoxicity varies significantly from the inherent risk at that B Total Furthermore, the bilirubin binding panel individualizes care because it helps to determine how aggressive intervention should be at any B Total , irrespective of whether it is above or below established B Total guidelines. The bilirubin binding panel may reduce anxiety, costs, unnecessary treatment, and the likelihood of undetected bilirubin neurotoxicity. Copyright © 2016 by the American Academy of Pediatrics.

Bilirubin and Stroke Risk Using a Mendelian Randomization Design.

Science.gov (United States)

Lee, Sun Ju; Jee, Yon Ho; Jung, Keum Ji; Hong, Seri; Shin, Eun Soon; Jee, Sun Ha

2017-05-01

Circulating bilirubin, a natural antioxidant, is associated with decreased risk of stroke. However, the nature of the relationship between the two remains unknown. We used a Mendelian randomization analysis to assess the causal effect of serum bilirubin on stroke risk in Koreans. The 14 single-nucleotide polymorphisms (SNPs) (bilirubin level in the KCPS-II (Korean Cancer Prevention Study-II) Biobank subcohort consisting of 4793 healthy Korean and 806 stroke cases. Weighted genetic risk score was calculated using 14 SNPs selected from the top SNPs. Both rs6742078 (F statistics=138) and weighted genetic risk score with 14 SNPs (F statistics=187) were strongly associated with bilirubin levels. Simultaneously, serum bilirubin level was associated with decreased risk of stroke in an ordinary least-squares analysis. However, in 2-stage least-squares Mendelian randomization analysis, no causal relationship between serum bilirubin and stroke risk was found. There is no evidence that bilirubin level is causally associated with risk of stroke in Koreans. Therefore, bilirubin level is not a risk determinant of stroke. © 2017 American Heart Association, Inc.

Bilirubin and its oxidation products damage brain white matter

Science.gov (United States)

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

Pulse radiolysis of bilirubin in aqueous solution

International Nuclear Information System (INIS)

Barber, D.J.W.; Richards, J.T.

1977-01-01

A pulse radiolysis study of bilirubin, the breakdown product of heme, has been made. In aqueous solution at pH 12, short-lived transient spectra have been obtained for reaction of bilirubin with e/sub aq//sup -/ and OH. Bimolecular rate constants for these reactions have been measured, namely, k/sub BR+e/sub aq//sup -/ equals 9.5 x 10 9 M -1 sec -1 and k/sub BR+OH/ equals 3.45 x 10 9 M -1 sec -1 , and the spectrum of a long-lived product resulting from decay of the bilirubin-OH adduct has been obtained. In addition, solute destruction by OH has been investigated in detail. The transient absorption spectrum for reduction of bilirubin with the H atom at neutral pH has been measured. By measuring the rate of reaction with e/sub aq//sup -/ in the presence of bovine serum albumin (BSA), the mode of binding of bilirubin to this biologically important compound has been studied

Quantitation of bilirubin conjugates with high-performance liquid chromatography in patients with low total serum bilirubin levels

NARCIS (Netherlands)

Jansen, P. L.; Cuypers, H. T.; Peters, W. H.

1984-01-01

Bilirubin mono- and diconjugates were determined by alkaline methanolysis and high-performance liquid chromatography (HPLC) in serum from patients with metastatic liver disease and liver cirrhosis. Conjugates could be detected and quantitated at normal or low total bilirubin levels. Comparison with

Bilirubin adsorption on nanocrystalline titania films

International Nuclear Information System (INIS)

Yang Zhengpeng; Si Shihui; Fung Yingsing

2007-01-01

Bilirubin produced from hemoglobin metabolism and normally conjugated with albumin is a kind of lipophilic endotoxin, and can cause various diseases when its concentration is high. Bilirubin adsorption on the nanocrystalline TiO 2 films was investigated using quartz crystal microbalance, UV-vis and IR techniques, and factors affecting its adsorption such as pH, bilirubin concentration, solution ionic strength, temperature and thickness of TiO 2 films were discussed. The amount of adsorption and parameters for the adsorption kinetics were estimated from the frequency measurements of quartz crystal microbalance. A fresh surface of the nanocrystalline TiO 2 films could be photochemically regenerated because holes and hydroxyl radicals were generated by irradiating the nanocrystalline TiO 2 films with UV light, which could oxidize and decompose organic materials, and the nanocrystalline TiO 2 films can be easily regenerated when it is used as adsorbent for the removal of bilirubin

Cells, bilirubin and light: formation of bilirubin photoproducts and cellular damage at defined wavelengths

International Nuclear Information System (INIS)

Christensen, T.; Kinn, G.; Granli, T.; Amundsen, I.

1994-01-01

Cultured cells from one human and one murine cell line were treated with bilirubin and irradiated with visible light of different wavelengths, either from phototherapy lamps or from a Xenon/Mercury lamp equipped with a monochromator. Bilirubin bound to human serum albumin was also irradiated with light. After irradiation, the bilirubin and its photoisomers were extracted with High Pressure Liquid Chromatography. The formation of single strand breaks in the DNA of treated cells was studied using a fluorescence marker. Cytotoxicity in the mouse skin cell line was measured by loss of the ability to form visible colonies in vitro. Green light exposure favours the production of lumirubin, while blue light causes more DNA damage and cytotoxicity. Green light may be more efficient and safer than shorter wavelength exposure when treating jaundiced newborns with phototherapy. 27 refs., 6 figs

A microscopic evaluation of collagen-bilirubin interactions: in vitro surface phenomenon.

Science.gov (United States)

Usharani, N; Jayakumar, G C; Rao, J R; Chandrasekaran, B; Nair, B U

2014-02-01

This study is carried out to understand the morphology variations of collagen I matrices influenced by bilirubin. The characteristics of bilirubin interaction with collagen ascertained using various techniques like XRD, CLSM, fluorescence, SEM and AFM. These techniques are used to understand the distribution, expression and colocalization patterns of collagen-bilirubin complexes. The present investigation mimic the in vivo mechanisms created during the disorder condition like jaundice. Fluorescence technique elucidates the crucial role played by bilirubin deposition and interaction during collagen organization. Influence of bilirubin during collagen fibrillogenesis and banding patterns are clearly visualize using SEM. As a result, collagen-bilirubin complex provides different reconstructed patterns because of the influence of bilirubin concentration. Selectivity, specificity and spatial organization of collagen-bilirubin are determined through AFM imaging. Consequently, it is observed that the morphology and quantity of the bilirubin binding to collagen varied by the concentrations and the adsorption rate in protein solutions. Microscopic studies of collagen-bilirubin interaction confirms that bilirubin influence the fibrillogenesis and alter the rate of collagen organization depending on the bilirubin concentration. This knowledge helps to develop a novel drug to inhibit the interface point of interaction between collagen and bilirubin. © 2013 The Authors Journal of Microscopy © 2013 Royal Microscopical Society.

Trans-Cutaneous Bilirubinometery versus Serum Bilirubin in Neonatal Jaundice.

Science.gov (United States)

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.

Comparison of serum bilirubin estimation with transcutaneous bilirubinometry in neonates

International Nuclear Information System (INIS)

Waqar, T.; Ahmad, Z.; Ali, A.

2010-01-01

Objective: To assess usefulness of Minolta Air shield transcutaneous bilirubinometer by comparing bilirubin values obtained by transcutaneous jaundice meter with serum bilirubin estimation. Design: Analytical cross sectional study. Place and duration: NICU Military Hospital Rawalpindi Pakistan Jun 2002 to May 2005. Subjects and Methods: One hundred and fifty neonates admitted to NICU because of visible jaundice were included in the study. Serum was sent to laboratory for total bilirubin estimation. At the same time bilirubin was also checked by a Jaundice Meter. Data was tabulated and t-test applied to compare the two values. Results: One hundred and fifty paired estimations were performed. The transcutaneous bilirubin values ranged from 8.0 mg/dl to 20.4 mg/dl. While serum bilirubin by jaundice meter values ranged between 5.3 mg/dl and 26.0 mg/dl. A Scatter diagram was plotted. It showed a correlation coefficient of 0.78. Conclusion: Bilirubin values obtained by transcutaneous bilirubin meter were not significantly different from laboratory values thus proving the fact that transcutaneous bilirubinometer is a useful device to measure bilirubin. (author)

Thermodynamic studies of bilirubin/cholesterol mixtures at the air/water interface

International Nuclear Information System (INIS)

Xie Anjian; Shen Yuhua; Xia Bing; Chen Hongbo; Ouyang Jianming

2005-01-01

Mixed monolayers of cholesterol and bilirubin spread at the air/water interface were used as model systems to examine the cholesterol effect on bilirubin. Miscibility and interactions between cholesterol and bilirubin were studied based on the analysis of the surface pressure-molecular area isotherms. From the isotherm data differentiated with respect to area, the condensing effect of cholesterol on the mixed monolayers could be observed distinctly. By studying surface compressibility modulus of bilirubin/cholesterol binary system vs. molecule area, we show that the liquid expanded-condensed phase transition (LE-C) of bilirubin was eliminated by cholesterol. In monolayers, bilirubin and cholesterol were found to be miscible at low surface pressure and immiscible at high surface pressure by studying the excess molecular areas of bilirubin/cholesterol system vs. mole fraction of bilirubin. The results from excess free energy of bilirubin/cholesterol system vs. mole fraction of bilirubin (X BR ) show that the maximum negative value of ΔG exc appeared at X BR =0.6, which indicates the formation of a bilirubin/cholesterol complex (M B-C ) of 3:2 stoichiometry as a result of the strong hydrogen bond between the polar groups of cholesterol and bilirubin and the self-assembly characteristics of cholesterol

Hepatocyte cotransport of taurocholate and bilirubin glucuronides: Role of microtubules

International Nuclear Information System (INIS)

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

1988-01-01

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 [ 14 C]bilirubin-[ 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 [ 14 C]bilirubin monoglucuronide-[ 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

Study of MRI characteristics of newborn bilirubin encephalopathy

International Nuclear Information System (INIS)

Wu Wulin; Wang Xiaoyi; Liao Weihua; Liu Fan; Zhang Ping

2008-01-01

Objective: To explore routine magnetic resonance imaging characteristics of newborn bilirubin encephalopathy (NBE). Methods: MRI features and clinical data of 17 patients with Newborn bilirubin encephalopathy were retrospectively analyzed, globus pallidus (GP)and subthalamic signal intensity was evaluated. The increase of GP signal intensity and serum total bilirubin peak value were analyzed using pearson correlation analysis. Serum total bilirubin peak value between patients with high signal in the subthalamic nuclei on T 1 WI and patients without high signal in the subthalamic nuclei were compared statistically. Results: The main MRI presentation in the NBE group was abnormally increased signal intensity in the GP on T 1 WI, which was not apparent on T 2 WI. One patient showed abnormal high signal intensity in the posteromedial part of GP. Nine patients had high signal in the subthalamic nuclei on T 1 WI and normal signal on T 2 WI. Four patients showed high signal in the brainstem with sparing of dorsal pontine. The increase in value of GP signal intensity was 249.0-423.8 in 12 patients and their serum total bilirubin peak values were 366.0-983.3 μmol/L. A positive correlation was found between increase of GP signal intensity and serum total bilirubin peak value. The serum total bilirubin level of abnormal subthalamic group and normal subthalamic group were 660.7±192.4 μmol/L and 513.3±107.51 μmol/L respectively. The difference between the two groups was not statistically significant (t=1.914, P>0.05). Conclusion: The routine MRI has some characteristics and is useful in the diagnosis of newborn bilirubin encephalopathy. (authors)

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

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Bilirubin (total or direct) test system. 862.1110... Systems § 862.1110 Bilirubin (total or direct) test system. (a) Identification. A bilirubin (total or direct) test system is a device intended to measure the levels of bilirubin (total or direct) in plasma...

Extreme Bilirubin Levels as a Causal Risk Factor for Symptomatic Gallstone Disease

DEFF Research Database (Denmark)

Stender, Stefan; Frikke-Schmidt, Ruth; Nordestgaard, Børge G

2013-01-01

In individuals without blockage of their bile ducts, levels of plasma bilirubin likely reflect levels of biliary bilirubin; higher biliary bilirubin levels may increase the risk of gallstone disease.......In individuals without blockage of their bile ducts, levels of plasma bilirubin likely reflect levels of biliary bilirubin; higher biliary bilirubin levels may increase the risk of gallstone disease....

Anti-Genotoxic Potential of Bilirubin In Vivo

DEFF Research Database (Denmark)

Wallner, Marlies; Antl, Nadja; Rittmannsberger, Barbara

2013-01-01

The bile pigment bilirubin is a known antioxidant and is associated with protection from cancer and cardiovascular disease (CVD) when present in too strong concentrations. Unconjugated bilirubin (UCB) might also possess anti-genotoxic potential by preventing oxidative damage to DNA. Moderately...... elevated bilirubin levels are found in individuals with Gilbert syndrome and more severe in the hyperbilirubinemic Gunn rat model. This study was therefore aimed to assess the levels of oxidative damage to DNA in Gilbert syndrome subjects and Gunn rats compared to matched controls. Seventy-six individuals...

beta-Glucuronidase-resistant bilirubin glucuronide isomers in cholestatic liver disease--determination of bilirubin metabolites in serum by means of high-pressure liquid chromatography

NARCIS (Netherlands)

Jansen, P. L.

1981-01-01

"Direct reacting bilirubin" in serum of patients with cholestatic liver disease and in serum of bile duct-ligated rats consists of a complex mixture of bilirubin metabolites. These metabolites were studied by means of high-pressure liquid chromatography. Bilirubin glucuronides in normal bile are

Enzymatic conversion of bilirubin monoglucuronide to diglucuronide by rat liver plasma membranes

NARCIS (Netherlands)

Jansen, P. L.; Chowdhury, J. R.; Fischberg, E. B.; Arias, I. M.

1977-01-01

Formation of bilirubin monoglucuronide from unconjugated bilirubin requires a microsomal enzyme, UDP-glucuronate glucuronyltransferase (EC 2.4.1.17). Conversion of bilirubin monoglucuronide to bilirubin diglucuronide, the major bilirubin conjugate in bile, was studied in subcellular fractions of rat

Conjugated Bilirubin Triggers Anemia by Inducing Erythrocyte Death

Science.gov (United States)

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

UDP-glucuronyltransferase-catalyzed deconjugation of bilirubin monoglucuronide

NARCIS (Netherlands)

Cuypers, H. T.; ter Haar, E. M.; Jansen, P. L.

1984-01-01

Bilirubin monoglucuronide is rapidly deconjugated when incubated with UDP and rat liver microsomal preparations at pH 5.1. The following evidence was found that this reaction is catalyzed by UDP-glucuronyltransferase: (i) unconjugated bilirubin and UDP-glucuronic acid were identified as the reaction

Development of bilirubin metabolism and transport in the neonate.

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Gartner, L M

1977-01-01

Comprehensive physiologic study of the developmental processes of bilirubin metabolism and transport reveal a complex interaction of various steps. Phase I Physiologic Jaundice results from the simultaneous increase in bilirubin load presented to the liver and decrease in bilirubin conjugating capacity. Phase II appears to result from a mild decrease in hepatic uptake capacity, coupled with the continuing increase in bilirubin load. Since these results are based upon studies of newborn rhesus monkeys, confirmatory studies in human neonates are required. Perhaps the most challenging aspect of these observations relates to the concept of a developmentally determined delicate imbalance between two functions. It is unlikely that pharmacologic agents could radically alter a single function. Therefore, it is perhaps more realistic to think that drug treatments which only slightly alter two functions simultaneously but in the appropriate directions could more effectively reduce the risk of toxicity. Thus, a mild increase in bilirubin conjugation coupled with a small but significant decrease in bilirubin load could markedly alleviate the severity of physiologic jaundice.

Ammonia-induced energy disorders interfere with bilirubin metabolism in hepatocytes.

Science.gov (United States)

Wang, Qiongye; Wang, Yanfang; Yu, Zujiang; Li, Duolu; Jia, Bin; Li, Jingjing; Guan, Kelei; Zhou, Yubing; Chen, Yanling; Kan, Quancheng

2014-08-01

Hyperammonemia and jaundice are the most common clinical symptoms of hepatic failure. Decreasing the level of ammonia in the blood is often accompanied by a reduction in bilirubin in patients with hepatic failure. Previous studies have shown that hyperammonemia can cause bilirubin metabolism disorders, however it is unclear exactly how hyperammonemia interferes with bilirubin metabolism in hepatocytes. The purpose of the current study was to determine the mechanism or mechanisms by which hyperammonemia interferes with bilirubin metabolism in hepatocytes. Cell viability and apoptosis were analyzed in primary hepatocytes that had been exposed to ammonium chloride. Mitochondrial morphology and permeability were observed and analyzed, intermediates of the tricarboxylic acid (TCA) cycle were determined and changes in the expression of enzymes related to bilirubin metabolism were analyzed after ammonia exposure. Hyperammonemia inhibited cell growth, induced apoptosis, damaged the mitochondria and hindered the TCA cycle in hepatocytes. This led to a reduction in energy synthesis, eventually affecting the expression of enzymes related to bilirubin metabolism, which then caused further problems with bilirubin metabolism. These effects were significant, but could be reversed with the addition of adenosine triphosphate (ATP). This study demonstrates that ammonia can cause problems with bilirubin metabolism by interfering with energy synthesis. Copyright © 2014 Elsevier Inc. All rights reserved.

Acute Alcohol Consumption Elevates Serum Bilirubin, an Endogenous Antioxidant

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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, pbilirubin 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

Preliminary development of a fiber optic sensor for measuring bilirubin.

Science.gov (United States)

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.

Prognostic significance of serum bilirubin in stroke

International Nuclear Information System (INIS)

Arslan, A.; Ismail, M.; Khan, F.; Khan, A.; Khattak, M.B.; Anwar, M.J.

2011-01-01

Background: Oxidative injury is an important cause of the neurologic lesion in stroke. Serum bilirubin is considered a natural antioxidant that may affect the prognosis of stroke. The purpose of this study was to evaluate the prognostic significance of bilirubin in stroke patients. Methods: A prospective cross-sectional study was conducted in Medical Units of Khyber Teaching Hospital, Peshawar. Inpatients admitted with acute attack of stroke were included in this study. Data regarding serum bilirubin and concurrent cerebrovascular risk factors were collected. National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) were used to analyse stroke's severity and functional outcomes, respectively. Results: Hypertension, diabetes mellitus and heart diseases were the most common risk factors. Patients were divided into 3 groups on the basis of serum bilirubin, i.e., =0.6 mg/dl (Group-1), 0.7-0.9 mg/dl (Group-2), and =1.0 mg/dl (Group-3). The mean pre-hospitalisation NIHSS score for Groups 1, 2 and 3 was 5.62, 11.66 and 25.33, respectively; and post-hospitalisation score was 0.875, 3.76 and 16.26, respectively. The pre-hospitalisation mRS score was 4 for Group-1, 4.52 for Group-2 and 4.93 for Group-3; while post-hospitalisation Mrs Score was 1.50, 2.38 and 4.26, respectively. Average serum bilirubin level was significantly higher in patients with poor outcomes as compared with good outcomes (p<0.01). Conclusions: This study suggests that higher serum bilirubin levels were associated with increased stroke severity, longer hospitalisation and poor prognosis. (author)

Preliminary Development of a Fiber Optic Sensor for Measuring Bilirubin

Directory of Open Access Journals (Sweden)

Steven M. Babin

2014-01-01

Full Text Available 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.

Membrane Transporters for Bilirubin and Its Conjugates: A Systematic Review

Directory of Open Access Journals (Sweden)

Jovana Čvorović

2017-12-01

Full Text Available Background: Bilirubin is a highly-hydrophobic tetrapyrrole which binds to plasma albumin. It is conjugated in the liver to glucuronic acid, and the water-soluble glucuronides are excreted in urine and bile. The membrane transporters of bilirubin diglucuronide are well-known. Still undefined are however the transporters performing the uptake of bilirubin from the blood into the liver, a process known to be fast and not rate-limited. The biological importance of this process may be appraised by considering that in normal adults 200–300 mg of bilirubin are produced daily, as a result of the physiologic turnover of hemoglobin and cellular cytochromes. Nevertheless, research in this field has yielded controversial and contradicting results. We have undertaken a systematic review of the literature, believing in its utility to improve the existing knowledge and promote further advancements.Methods: We have sourced the PubMed database until 30 June 2017 by applying 5 sequential searches. Screening and eligibility criteria were applied to retain research articles reporting results obtained by using bilirubin molecules in membrane transport assays in vitro or by assessing serum bilirubin levels in in vivo experiments.Results: We have identified 311 articles, retaining 44, reporting data on experimental models having 6 incremental increases of complexity (isolated proteins, membrane vesicles, cells, organ fragments, in vivo rodents, and human studies, demonstrating the function of 19 membrane transporters, encoded by either SLCO or ABC genes. Three other bilirubin transporters have no gene, though one, i.e., bilitranslocase, is annotated in the Transporter Classification Database.Conclusions: This is the first review that has systematically examined the membrane transporters for bilirubin and its conjugates. Paradoxically, the remarkable advancements in the field of membrane transport of bilirubin have pointed to the elusive mechanism(s enabling

Reduced total serum bilirubin levels are associated with ulcerative colitis.

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Kathleen M Schieffer

Full Text Available Chronic inflammation associated with inflammatory bowel disease (IBD results in increased oxidative stress that damages the colonic microenvironment. Low levels of serum bilirubin, an endogenous antioxidant, have been associated with increased risk for Crohn's disease (CD. Therefore, the aim of this study was to examine whether total serum bilirubin levels are associated with ulcerative colitis (UC. We identified a retrospective case-control population (n = 6,649 from a single tertiary care center, Penn State Hershey Medical Center (PSU and a validation cohort (n = 1,996 from Virginia Commonwealth University Medical Center (VCU. Cases were age- and sex-matched to controls (PSU: CD n = 254, UC n = 187; VCU: CD n = 233, UC n = 124. Total serum bilirubin levels were obtained from de-identified medical records and segregated into quartiles. Logistic regression analysis was performed on each quartile of total serum bilirubin compared to the last quartile (highest bilirubin levels to determine the association of total serum bilirubin with UC. Similar to CD patients, UC patients demonstrated reduced levels of total serum bilirubin compared to controls at PSU and VCU. The lowest quartile of total serum bilirubin was independently associated with UC for the PSU (OR: 1.98 [95% CI: 1.09-3.63] and VCU cohorts (OR: 6.07 [95% CI: 3.01-12.75]. Lower levels of the antioxidant bilirubin may reduce the capability of UC patients to remove reactive oxygen species leading to an increase in intestinal injury. Therapeutics that reduce oxidative stress may be beneficial for these patients.

Metabolism of bilirubin by human cytochrome P450 2A6

Energy Technology Data Exchange (ETDEWEB)

Abu-Bakar, A' edah, E-mail: a.abubakar@uq.edu.au [The University of Queensland, National Research Centre for Environmental Toxicology (Entox), 4072 Brisbane, Queensland (Australia); Arthur, Dionne M. [The University of Queensland, National Research Centre for Environmental Toxicology (Entox), 4072 Brisbane, Queensland (Australia); Cooperative Research Centre for Contamination Assessment and Remediation of the Environment, Adelaide (Australia); Wikman, Anna S. [The University of Queensland, National Research Centre for Environmental Toxicology (Entox), 4072 Brisbane, Queensland (Australia); Department of Pharmaceutical Biosciences, Uppsala University, SE-75123 Uppsala (Sweden); Rahnasto, Minna; Juvonen, Risto O.; Vepsäläinen, Jouko; Raunio, Hannu [School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, POB 1627, 70211 Kuopio (Finland); Ng, Jack C. [The University of Queensland, National Research Centre for Environmental Toxicology (Entox), 4072 Brisbane, Queensland (Australia); Cooperative Research Centre for Contamination Assessment and Remediation of the Environment, Adelaide (Australia); Lang, Matti A. [The University of Queensland, National Research Centre for Environmental Toxicology (Entox), 4072 Brisbane, Queensland (Australia)

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

Metabolism of bilirubin by human cytochrome P450 2A6

International Nuclear Information System (INIS)

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.

2012-01-01

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 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 CYP2A6

Microsomal UDP-glucuronyltransferase-catalyzed bilirubin diglucuronide formation in human liver

NARCIS (Netherlands)

Peters, W. H.; Jansen, P. L.

1986-01-01

Human liver microsomal bilirubin UDP-glucuronyltransferase catalyzes formation of bilirubin mono- and diglucuronide. KmUDPGA and Vmax of the enzyme are 0.6 mM and 1.69 nmol/mg protein X min. In vitro, bilirubin readily dissolves in the microsomal lipid phase. Taking this into account a Kmbilirubin

Percutaneous biliary drainage effectively lowers serum bilirubin to permit chemotherapy treatment.

Science.gov (United States)

Levy, Jennifer L; Sudheendra, Deepak; Dagli, Mandeep; Mondschein, Jeffrey I; Stavropoulos, S William; Shlansky-Goldberg, Richard D; Trerotola, Scott O; Teitelbaum, Ursina; Mick, Rosemarie; Soulen, Michael C

2016-02-01

For digestive tract cancers, the bilirubin threshold for administration of systemic chemotherapy can be 5 or 2 mg/dL (85.5 or 34.2 μmol/L) depending upon the regimen. We examined the ability of percutaneous biliary drainage (PBD) in patients with malignant biliary obstruction to achieve these clinically relevant endpoints. 106 consecutive patients with malignant biliary obstruction and a baseline serum bilirubin >2 mg/dL underwent PBD. Time to achieve a bilirubin of 5 mg/dL (85.5 μmol/L), 2 mg/dL (34.2 μmol/L), and survival was estimated by Kaplan-Meier analysis. Potential technical and clinical prognostic factors were subjected to univariate and multivariate analysis. Categorical variables were analyzed by the log rank test. Hazard ratios were calculated for continuous variables. Median survival was 100 days (range 1-3771 days). Among 88 patients with a pre-drainage bilirubin >5 mg/dL, 62% achieved a serum bilirubin ≤5 mg/dL within 30 days and 84% within 60 days, median 21 days. Among 106 patients with a pre-drainage bilirubin >2 mg/dL, 37% achieved a serum bilirubin ≤2 mg/dL by 30 days and 70% within 60 days, median 43 days. None of the technical or clinical factors evaluated, including pre-drainage bilirubin, were significant predictors of time to achieve a bilirubin ≤2 mg/dL (p = 0.51). Size and type of biliary device were the only technical variables found to affect time to bilirubin of 5 mg/dL (p = 0.016). PBD of malignant obstruction achieves clinically relevant reduction in serum bilirubin in the majority of patients within 1-2 months, irrespective of the pre-drainage serum bilirubin, sufficient to allow administration of systemic chemotherapy. However, the decision to undergo this procedure for this indication alone must be considered in the context of patients' prognosis and treatment goals.

Revalidation and rationale for high pKa values of unconjugated bilirubin

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Ostrow J Donald

2007-05-01

Full Text Available Abstract 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

PPARα: A Master Regulator of Bilirubin Homeostasis

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Cyril Bigo

2014-01-01

Full Text Available 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.

Influence of hemoglobin on non-invasive optical bilirubin sensing

Science.gov (United States)

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.

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

Science.gov (United States)

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

Enterohepatic circulation of nonconjugated bilirubin in rats fed with human milk

International Nuclear Information System (INIS)

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

1991-01-01

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

Does bilirubin prevent hepatic steatosis through activation of the PPARα nuclear receptor?

Science.gov (United States)

Hinds, Terry D; Adeosun, Samuel O; Alamodi, Abdulhadi A; Stec, David E

2016-10-01

Several large population studies have demonstrated a negative correlation between serum bilirubin levels and the development of obesity, hepatic steatosis, and cardiovascular disease. Despite the strong correlative data demonstrating the protective role of bilirubin, the mechanism by which bilirubin can protect against these pathologies remains unknown. Bilirubin has long been known as a powerful antioxidant and also has anti-inflammatory actions, each of which may contribute to the protection afforded by increased levels. We have recently described a novel function of bilirubin as a ligand for the peroxisome proliferator-activated receptor-alpha (PPARα), which we show specifically binds to the nuclear receptor. Bilirubin may function as a selective PPAR modulator (SPPARM) to control lipid accumulation and blood glucose. However, it is not known to what degree bilirubin activation of PPARα is responsible for the protection afforded to reduce hepatic steatosis. We hypothesize that bilirubin, acting as a novel SPPARM, increases hepatic fatty acid metabolism through a PPARα-dependent mechanism which reduces hepatic lipid accumulation and protects against hepatic steatosis and non-alcoholic fatty liver disease (NAFLD). Copyright © 2016 Elsevier Ltd. All rights reserved.

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

Science.gov (United States)

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.

Bilirubin nanoparticle preconditioning protects against hepatic ischemia-reperfusion injury.

Science.gov (United States)

Kim, Jin Yong; Lee, Dong Yun; Kang, Sukmo; Miao, Wenjun; Kim, Hyungjun; Lee, Yonghyun; Jon, Sangyong

2017-07-01

Hepatic ischemia-reperfusion injury (IRI) remains a major concern in liver transplantation and resection, despite continuing efforts to prevent it. Accumulating evidence suggests that bilirubin possesses antioxidant, anti-inflammatory and anti-apoptotic properties. However, despite obvious potential health benefits of bilirubin, its clinical applications are limited by its poor solubility. We recently developed bilirubin nanoparticles (BRNPs) consisting of polyethylene glycol (PEG)-conjugated bilirubin. Here, we sought to investigate whether BRNPs protect against IRI in the liver by preventing oxidative stress. BRNPs exerted potent antioxidant and anti-apoptotic activity in primary hepatocytes exposed to hydrogen peroxide, a precursor of reactive oxygen species (ROS). In a model of hepatic IRI in mice, BRNP preconditioning exerted profound protective effects against hepatocellular injury by reducing oxidative stress, pro-inflammatory cytokine production, and recruitment of neutrophils. They also preferentially accumulated in IRI-induced inflammatory lesions. Collectively, our findings indicate that BRNP preconditioning provides a simple and safe approach that can be easily monitored in the blood like endogenous bilirubin, and could be a promising strategy to protect against IRI in a clinical setting. Copyright © 2017 Elsevier Ltd. All rights reserved.

The kinetics of oxidation of bilirubin and ascorbic acid in solution

Science.gov (United States)

Solomonov, A. V.; Rumyantsev, E. V.; Kochergin, B. A.; Antina, E. V.

2012-07-01

The results of a comparative study of the oxidation of bilirubin, ascorbic acid, and their mixture in aqueous solutions under the action of air oxygen and hydrogen peroxide are presented. The observed and true rate constants for the oxidation reactions were determined. It was shown that the oxidation of tetrapyrrole pigment occurred under these conditions bypassing the stage of biliverdin formation to monopyrrole products. Simultaneous oxidation of bilirubin and ascorbic acid was shown to be accompanied by the inhibition of ascorbic acid oxidation by bilirubin, whereas ascorbic acid itself activated the oxidation of bilirubin.

Investigation on 3H-labelled bilirubin for study of blood-brain barrier

International Nuclear Information System (INIS)

Cao Rongzhen; Dong Mo; Zhang Yulong; Zhou Ruiju

1996-01-01

Synthesis of 3 H-labelled bilirubin is described. 3 H-bilirubin is prepared by the reduction of biliverdin using sodium boro-[ 3 H]-hydride in methanol solvent. But biliverdin is synthesized through dehydrogenation of bilirubin with 2,3- dichloro-5, 6-dicyanobenzoquinone (DDQ) in dimethyl sulphoxide and sodium boro-[ 3 H]-hydride is produced by exchange of sodium boro-hydride with tritium gas using nickel catalyst at high temperature. The specific activity of obtained 3 H-bilirubin is 306 GBq/mmol, while the radiochemical purity is over 95% by HPLC and paper chromatography. The permeated profile of 3 H-labelled bilirubin in rat brain has been obtained in animal experiments

Enzymatic Removal of Bilirubin from Blood: A Potential Treatment for Neonatal Jaundice

Science.gov (United States)

Lavin, Arthur; Sung, Cynthia; Klibanov, Alexander M.; Langer, Robert

1985-11-01

Current treatments for severe jaundice can result in major complications. Neonatal jaundice is caused by excessive accumulation of bilirubin in the blood. A small blood filter containing immobilized bilirubin oxidase was developed to reduce serum bilirubin concentrations. When human or rat blood was passed through the enzyme filter, more than 90 percent of the bilirubin was degraded in a single pass. This procedure may have important applications in the clinical treatment of neonatal jaundice.

Does bilirubin protect against hemochromatosis gene (HFE) related mortality?

NARCIS (Netherlands)

Alizadeh, Behrooz Z.; Njajou, Omer T.; Houwing-Duistermaat, Jeanine J.; de Jong, Gerard; Vergeer, Jeannette M.; Hofman, Albert; Pols, Huibert A.P.; van Duijn, Cornelia M.

2004-01-01

Serum bilirubin is an important antioxidant that is found at increased levels in hereditary hemochromatosis patients. We hypothesized that increased levels of serum bilirubin may play a protective role against oxidative stress induced by iron overload in carriers of mutations in the hereditary

Unconjugated Bilirubin Inhibits Proteolytic Cleavage of von Willebrand Factor by ADAMTS13 Protease

Science.gov (United States)

Lu, Rui-Nan; Yang, Shangbin; Wu, Haifeng M.; Zheng, X. Long

2015-01-01

Summary Background Bilirubin is a yellow breakdown product of heme catabolism. Increased serum levels of unconjugated bilirubin are conditions commonly seen in premature neonates and adults with acute hemolysis including thrombotic microangiopathy. Previous studies have shown that unconjugated bilirubin lowers plasma ADAMTS13 activity, but the mechanism is not fully understood. Objectives The study is to determine whether unconjugated bilirubin directly inhibits the cleavage of von Willebrand factor (VWF) and its analogs by ADAMTS13. Methods Fluorogenic, SELDI-TOF mass spectrometric assay, and Western blotting analyses were employed to address this question. Results Unconjugated bilirubin inhibits the cleavage of F485-rVWF73-H, D633-rVWF73-H, and GST-rVWF71-11K by ADAMTS13 in a concentration-dependent manner with a half-maximal inhibitory concentration (IC50) of ~13 μM, ~70 μM, and ~17 μM, respectively. Unconjugated bilirubin also dose-dependently inhibits the cleavage of multimeric VWF by ADAMTS13 under denaturing conditions. The inhibitory activity of bilirubin on the cleavage of D633-rVWF73-H and multimeric VWF, but not F485-rVWF73-H, was eliminated after incubation with bilirubin oxidase that converts bilirubin to biliverdin. Furthermore, plasma ADAMTS13 activity in patients with hyperbilirubinemia is lower prior to than after treatment with bilirubin oxidase. Conclusions unconjugated bilirubin directly inhibits ADAMTS13’s ability to cleave both peptidyl and native VWF substrates in addition to its interference with certain fluorogenic assays. Our findings may help proper interpretation of ADAMTS13 results under pathological conditions. Whether elevated serum unconjugated bilirubin has an adverse effect in vivo remains to be determined in our future study. PMID:25782102

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

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Urinary bilirubin and its conjugates... Clinical Chemistry Test Systems § 862.1115 Urinary bilirubin and its conjugates (nonquantitative) test system. (a) Identification. A urinary bilirubin and its conjugates (nonquantitative) test system is a...

Bilirubin-Induced Neurological Dysfunction: A Clinico-Radiological-Neurophysiological Correlation in 30 Consecutive Children.

Science.gov (United States)

van Toorn, Ronald; Brink, Philip; Smith, Johan; Ackermann, Christelle; Solomons, Regan

2016-12-01

The clinical expression of bilirubin-induced neurological dysfunction varies according to severity and location of the disease. Definitions have been proposed to describe different bilirubin-induced neurological dysfunction subtypes. Our objective was to describe the severity and clinico-radiological-neurophysiological correlation in 30 consecutive children with bilirubin-induced neurological dysfunction seen over a period of 5 years. Thirty children exposed to acute neonatal bilirubin encephalopathy were included in the study. The mean peak total serum bilirubin level was 625 μmol/L (range 480-900 μmol/L). Acoustic brainstem responses were abnormal in 73% (n = 22). Pallidal hyperintensity was observed on magnetic resonance imaging in 20 children. Peak total serum bilirubin levels correlated with motor severity (P = .03). Children with severe motor impairment were likely to manifest severe auditory neuropathy (P bilirubin-induced neurological dysfunction subtype, and the majority of children had abnormal acoustic brainstem responses and magnetic resonance imaging. © The Author(s) 2016.

Antioxidant mechanism of bilirubin: both HAT and SET are possible

International Nuclear Information System (INIS)

Adhikari, Soumyakanti; Joshi, Ravi; Mukherjee, Tulsi

2008-01-01

Bilirubin (BR) plays two extreme roles in physiology, one hand it is a toxic metabolite while at micromolar concentration it acts as antioxidant. It has been observed that hydroxyl, glutathiyl and Linoleic peroxyl radicals abstract hydrogen atom from bilirubin, whereas N 3 , Br 2 , CCl 3 OO, NO 2 radicals react via single electron transfer action. Our study demonstrates that oxidation of bilirubin occurs via both hydrogen atom transfer and single electron transfer depending on the nature of the radical. (author)

Liver function test with 99mTc-labelled bilirubin in children

International Nuclear Information System (INIS)

Teichmann, B.; Kaempfer, I.; Schneider, G.

1989-01-01

Because of central role of bilirubin in the metabolism of liver it is well suited for liver function tests. Different parameters of hepatocellular partial function and histological findings were studied in patients suffering from functional hyperbilirubinaemia (n = 15), liver cirrhosis (n = 7) and 6 patients recovering from acute hepatitis. After intravenous injection of 99m Tc-bilirubin blood clearance and intestinal excretion in percentages of bilirubin were determined. In patients with cirrhosis the initial phase as well as the intestinal excretion of bilirubin were delayed. This liver function test is useful in the pediatric special diagnosis for investigations during the course of the illness and for assessment of therapeutic activities. (author)

Unconjugated free bilirubin in preterm infants.

Science.gov (United States)

van der Schoor, Lori W E; Dijk, Peter H; Verkade, Henkjan J; Kamsma, Anna C J; Schreuder, Andrea B; Groen, Henk; Hulzebos, Christian V

Hyperbilirubinemia guidelines are based on total serum bilirubin (TSB), in combination with either gestational age (GA) or birth weight (BW), postnatal age and specific risk factors. However, TSB is a poor predictor of bilirubin-induced neurotoxicity (BIND). Free unconjugated bilirubin (UCBfree) and the UCBfree/TSB ratio are more directly related to BIND, but data on their postnatal courses are unknown. To characterize the postnatal courses of UCBfree and UCBfree/TSB ratio, and assess their relationships with clinical characteristics. 72 preterm infants≤32weeks GA, admitted to the University Medical Center Groningen, The Netherlands. During the first postnatal week, bilirubin plasma parameters were analyzed and their relationship with clinical parameters was analyzed. Postnatal changes were analyzed using Generalized Estimating Equations. Data are expressed as medians [ranges]. Less than 10% of the cohort (GA: 29 [26-31] weeks; BW: 1165 [600-1975] g) showed hyperbilirubinemic risk factors. We observed a large variation in UCBfree (27 [1-197] nmol/L), that could partly be explained by postnatal age and gender, but not by other risk factors. Maximal UCBfree levels of 50 [13-197] nmol/L occurred at day 4 and were higher in males. In contrast to TSB, UCBfree/TSB ratios (0.19 [0.01-1.04]) were higher in infants with low GA/BW. UCBfree levels vary considerably in preterm infants, despite a low incidence of hyperbilirubinemic risk factors and similar TSB-based phototherapy treatment. UCBfree could not be predicted by GA or BW, but UCBfree/TSB ratios are highest in the smallest preterms, while they have the lowest TSB levels. Copyright © 2017 Elsevier B.V. All rights reserved.

Determination of cholesterol, calcium carbonate and bilirubinate of gallstone

International Nuclear Information System (INIS)

Iqbal, Y.; Nazneen, B.I.

2004-01-01

Gallstones of seven patients were collected from different parts of North West Frontier and Punjab provinces. These stones were analyzed using Liebermann-Burchard method, estimation technique and Microlab-200 for cholesterol, calcium carbonate (CaCO/sub 3/) and bilirubinate respectively. The levels of cholesterol bilirubinate and CaCO/sub 3/ were found in the ranges of 50-81, 12-40 and 7-19% respectively. All of the stones were found to be mixed type stones that contain cholesterol, bilirubinate and calcium carbonate. The structures of the stones are also shown in the picture, which confirm our analysis data. Possible reasons, which cause formation of gallstones, are discussed in this paper. (author)

The relationship between serum bilirubin level with interleukin.6 ...

African Journals Online (AJOL)

Context: Bilirubin has been shown to influence the mechanisms of both apoptosis and inflammation. Aims: The aim of the following study is to investigate the relationship between the serum bilirubin level with sepsis progression. Settings and Design: A total of 20 patients from intensive care unit were included for this study.

Laser Transcutaneous Bilirubin Meter: A New Device For Bilirubin Monitoring In Neonatal Jaundice

Science.gov (United States)

Hamza, Mostafa; Hamza, Mohammad

1988-06-01

Neonates with jaundice require monitoring of serum bilirubin which should be repeated at frequent intervals. However, taking blood samples from neonates is not always an easy job, plus being an invasive and traumatising procedure with the additional risk of blood loss. In this paper the authors present the theory and design of a new noninvasive device for transcutaneous bilirubinometry, using a differential absorption laser system. The new technique depends upon illuminating the skin of the neonate with radiation from a two wave-length oscillation laser. The choice of the wavelengths follows the principles of optical bilirubinometry. For obtaining more accurate measurements, different pairs of two wave-lengths are incorporated in the design. The presence of hemoglobin is corrected for by appropriate selection of the laser wavelengths. The new design was tested for accuracy and precision using an argon ion laser. Correlation study between serum bilirubin determination by laser transcutaneous bilirubinometry and by American optical bilirubinometer was highly significant.

Elevated bilirubin levels are associated with a better renal prognosis and ameliorate kidney fibrosis.

Science.gov (United States)

Park, Sehoon; Kim, Do Hyoung; Hwang, Jin Ho; Kim, Yong-Chul; Kim, Jin Hyuk; Lim, Chun Soo; Kim, Yon Su; Yang, Seung Hee; Lee, Jung Pyo

2017-01-01

Bilirubin has been reported to protect against kidney injury. However, further studies highlighting the beneficial effects of bilirubin on renal fibrosis and chronic renal function decline are necessary. We assessed a prospective cohort with a reference range of total bilirubin levels. The primary outcome was a 30% reduction in the estimated glomerular filtration rate (eGFR) from baseline, and the secondary outcome was a doubling of the serum creatinine levels, halving of the eGFR and the initiation of dialysis. In addition, experiments with tubular epithelial cells and C57BL/6 mice were performed to investigate the protective effects of bilirubin on kidney fibrosis. As a result, 1,080 patients were included in the study cohort. The study group with relative hyperbilirubinemia (total bilirubin 0.8-1.2 mg/dL) showed a better prognosis in terms of the primary outcome (adjusted hazard ratio (HR) 0.33, 95% confidence interval (CI) 0.19-0.59, P bilirubin-treated mice showed less fibrosis in the unilateral ureteral obstruction (UUO) model (P bilirubin treatment decreased fibronectin expression in tubular epithelial cells in a dose-dependent manner (P bilirubin levels were associated with better renal prognosis, and bilirubin treatment induced a beneficial effect on renal fibrosis. Therefore, bilirubin could be a potential therapeutic target to delay fibrosis-related kidney disease progression.

Bilirubin Albumin Binding and Unbound Unconjugated Hyperbilirubinemia in Premature Infants.

Science.gov (United States)

Amin, Sanjiv B; Wang, Hongyue

2018-01-01

To evaluate the associations between unbound bilirubin (UB) and total serum bilirubin (TSB), bilirubin:albumin molar ratio (BAMR), and bilirubin albumin binding affinity (Ka) as a function of gestational age (GA) in infants born at 24-33 weeks GA. In a prospective observational study, TSB and UB were measured twice daily at least 8 hours apart during the first postnatal week. Serum albumin was measured to calculate BAMR on each day. The highest UB on each day, corresponding TSB, and serum albumin were used to calculate the Ka on each day. For the 166 infants studied, peak UB significantly correlated with concomitant Ka (r = -0.44, P = .001) but not with concomitant TSB or BAMR after adjusting for GA. On multiple regression analyses, there was a significant association of concomitant Ka (-0.06, 95% CI -0.08 to -0.04, P = .0001), but not concomitant TSB or BAMR with peak UB after controlling for GA, birth weight, race, and sex. GA group was a significant effect modifier for the association between Ka and peak UB (0.03, 95% CI 0.02-0.04, P bilirubin-induced neurotoxicity. Copyright © 2017 Elsevier Inc. All rights reserved.

Change in Serum Bilirubin Level as a Predictor of Incident Metabolic Syndrome.

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Lee, You-Bin; Lee, Seung-Eun; Jun, Ji Eun; Jee, Jae Hwan; Bae, Ji Cheol; Jin, Sang-Man; Kim, Jae Hyeon

2016-01-01

Serum bilirubin level was negatively associated with the prevalence of metabolic syndrome (MetS) in previous cross-sectional studies. However, bilirubin variance preceding the development of MetS has yet to be investigated. We aimed to determine the effect of change in bilirubin concentration on the risk of incident MetS in healthy Korean adults. We conducted a retrospective longitudinal study of subjects who had undergone at least four yearly health check-ups between 2006 and 2012. Of 24,185 total individuals who received annual check-ups, 11,613 non-MetS participants with a baseline bilirubin level not exceeding 34.2 μmol/l were enrolled. We evaluated the association between percent change in bilirubin and risk of incident MetS. During 55,407 person-years of follow-up, 2,439 cases of incident MetS developed (21.0%). Baseline serum bilirubin level clearly showed no association with the development of MetS in men but an independent significant inverse association in women which attenuated (hence may be mediated) by elevated homeostatic model assessment index 2 for insulin resistance (HOMA2-IR). However, increased risk for incident MetS was observed in higher percent change in bilirubin quartiles, with hazard ratios of 2.415 (95% CI 2.094-2.785) in men and 2.156 (95% CI 1.738-2.675) in women in the fourth quartile, compared to the lowest quartile, after adjusting for age, smoking status, medication history, alanine aminotransferase, uric acid, estimated glomerular filtration rate, fasting glucose, baseline diabetes mellitus prevalence, systolic blood pressure, waist circumference, and body mass index. The hazard ratios per one standard deviation increase in percent change in bilirubin as a continuous variable were 1.277 (95% CI 1.229-1.326) in men and 1.366 (95% CI 1.288-1.447) in women. Increases in serum bilirubin concentration were positively associated with a higher risk of incident MetS. Serum bilirubin increment might be a sensitive marker for the development

Bilirubin UDP-glucuronosyltransferase 1 is the only relevant bilirubin glucuronidating isoform in man

NARCIS (Netherlands)

Bosma, P. J.; Seppen, J.; Goldhoorn, B.; Bakker, C.; Oude Elferink, R. P.; Chowdhury, J. R.; Chowdhury, N. R.; Jansen, P. L.

1994-01-01

Crigler-Najjar syndrome type I (CN-I) is caused by an inherited absence of UDP-glucuronosyltransferase activity toward bilirubin (B-UGT), resulting in severe non-hemolytic unconjugated hyperbilirubinemia. Based on the expression of cDNAs in COS cells, two UGT isoforms in human liver, B-UGT1 and

Serum Bilirubin and Their Association With C-Reactive Protein in Patients With Migraine.

Science.gov (United States)

Peng, You-Fan; Xie, Li-Qiu; Xiang, Yang; Xu, Gui-Dan

2016-11-01

Increased levels of C-reactive protein (CRP) have been considered as a marker in assessing neurogenic inflammation of migraine patients. An inverse relationship between serum bilirubin and CRP has been observed in various diseases. Therefore, we analyzed serum bilirubin levels in migraine patients, and investigated the relationship between serum bilirubin and CRP in migraineurs. A total of 86 newly diagnosed migraine patients were consecutively recruited to this study. Significantly lower median serum total bilirubin, conjugated bilirubin (CB) and unconjugated bilirubin were found in patients with migraine than healthy controls, and the levels of CRP were significantly higher in migraine patients than healthy controls. A negative correlation between CRP and CB was observed in patients with migraine (r = -0.255, P = 0.018). In a multiple linear regression model, the concentrations of CRP remained negatively correlated with CB. Our study demonstrates that serum bilirubin concentrations are decreased in migraineurs, and CB levels were found to be positively correlated with CRP in migraine patents. However, larger cross-sectional and prospective studies are needed to establish whether serum bilirubin may be a useful biomarker for assessing neurogenic inflammation in migraine patients and eventually guiding the therapy. © 2016 Wiley Periodicals, Inc.

Labelling of bilirubin with /sup 99m/Tc and pharmacokinetic behavior

International Nuclear Information System (INIS)

Kaempfer, I.; Schneider, G.; Blottner, A.; Deckart, H.; Staedtisches Klinikum Berlin-Buch

1982-01-01

The yield of the bilirubin labelling with /sup 99m/Tc amounted to 97%. The labelled complex has been stable for 24 hours with the pH range 2-7.5. As evidenced in animal experiments the labelled bilirubin is probably subjected to natural degradation processes. Side effects could not be noticed. A disadvantage seems to be the slow transfer of /sup 99m/Tc-bilirubin from the hepatic cell to the biliary capillary

IN VITRO CHEMO-PREVENTATIVE ACTIVITY OF STRELITZIA NICOLAI ARIL EXTRACT CONTAINING BILIRUBIN.

Science.gov (United States)

Dwarka, Depika; Thaver, Veneesha; Naidu, Mickey; Koorbanally, Neil A; Baijnath, And Himansu

2017-01-01

The discovery of the only animal pigment, bilirubin, in the plant Strelitzia nicolai has triggered a vast number of questions regarding bilirubin's formation and its role in the human body. Recent studies have confirmed that bilirubin at certain levels have many medical benefits. Various case studies have revealed that bilirubin is a potent antioxidant. Cervical cancer is one of South Africa's largest womens' health crises. It is estimated that it affects one out of 41 South African women and kills approximately 8 women in the country every day. Thus, the aim of this study was to investigate if the aril extract of Strelitzia nicolai (Regel and Körn.) containing bilirubin possesses anti-cancer activity and to determine its effect on the induction of apoptosis. The DPPH activity was firstly used to determine the antioxidant effect of the extract. Thereafter, the cytotoxic effect was tested using the XTT assay. Apoptosis was confirmed and quantified using the Annexin V-PE kit and the morphology was studied using acridine orange and ethidium bromide. The aril extract decreased cell viability by 52% and induced apoptosis in HeLa cells; as shown by the Annexin V-PE Apoptosis detection kit and morphological studies with acridine orange/ethidium bromide staining. The activity of the extract as a potent antioxidant was immensely enhanced as compared to the bilirubin standard. These results suggest that S. nicolai aril extract containing bilirubin works synergistically as opposed to bilirubin on its own. Furthermore, this extract might be a good candidate for the therapeutic intervention of cervical cancer.

Bilirubin levels and phototherapy use before and after neonatal red blood cell transfusions.

Science.gov (United States)

Carroll, Patrick D; Christensen, Robert D; Baer, Vickie L; Sheffield, Mark J; Gerday, Erick; Ilstrup, Sarah J

2016-11-01

Our previous retrospective study suggested that red blood cell (RBC) transfusion of preterm neonates can be associated with an increase in bilirubin, but this has not been tested prospectively. We studied neonates before and after RBC transfusions, recording serial bilirubin levels and whether they qualified for phototherapy. Because lysed RBCs release plasma-free hemoglobin (Hb), a precursor to bilirubin, we also measured plasma free Hb and bilirubin from the donor blood. We studied 50 transfusions given to 39 neonates. Gestation ages of transfused neonates, at birth, were 26 (24-29) weeks (median [interquartile range]); birthweights were 750 (620-1070) g. The study transfusion was given on Day of Life 9.9 (3.4-19.2). In 20% (10/50) phototherapy was being administered at the beginning of and during the transfusion. In these patients neither the 4- to 6- nor the 24- to 36-hour-posttransfusion bilirubin levels were significantly higher than before transfusion. However, in 30% of the others (12/40) phototherapy was started (or restarted) after the transfusion and 15% had a posttransfusion bilirubin increase of at least 2.5 mg/dL. These neonates received donor blood with a higher plasma-free Hb (p bilirubin increase of at least 2.5 mg/dL. We speculate that neonates qualifying for a RBC transfusion, who are judged to be at high risk for bilirubin-induced neurotoxicity, might benefit from checking their serum bilirubin level after the transfusion and providing donor blood with low plasma-free Hb levels. © 2016 AABB.

Bilirubin Modulates Acetylcholine Receptors In Rat Superior Cervical Ganglionic Neurons In a Bidirectional Manner

Science.gov (United States)

Zhang, Chengmi; Wang, Zhenmeng; Dong, Jing; Pan, Ruirui; Qiu, Haibo; Zhang, Jinmin; Zhang, Peng; Zheng, Jijian; Yu, Weifeng

2014-01-01

Autonomic dysfunction as a partial contributing factor to cardiovascular instability in jaundiced patients is often associated with increased serum bilirubin levels. Whether increased serum bilirubin levels could directly inhibit sympathetic ganglion transmission by blocking neuronal nicotinic acetylcholine receptors (nAChRs) remains to be elucidated. Conventional patch-clamp recordings were used to study the effect of bilirubin on nAChRs currents from enzymatically dissociated rat superior cervical ganglia (SCG) neurons. The results showed that low concnetrations (0.5 and 2 μM) of bilirubin enhanced the peak ACh-evoked currents, while high concentrations (3 to 5.5 µM) of bilirubin suppressed the currents with an IC50 of 4 ± 0.5 μM. In addition, bilirubin decreased the extent of desensitization of nAChRs in a concentration-dependent manner. This inhibitory effect of bilirubin on nAChRs channel currents was non-competitive and voltage independent. Bilirubin partly improved the inhibitory effect of forskolin on ACh-induced currents without affecting the action of H-89. These data suggest that the dual effects of enhancement and suppression of bilirubin on nAChR function may be ascribed to the action mechanism of positive allosteric modulation and direct blockade. Thus, suppression of sympathetic ganglionic transmission through postganglionic nAChRs inhibition may partially contribute to the adverse cardiovascular effects in jaundiced patients. PMID:25503810

Genetically elevated bilirubin and risk of ischaemic heart disease

DEFF Research Database (Denmark)

Stender, Stefan; Frikke-Schmidt, R; Nordestgaard, B G

2013-01-01

Elevated plasma levels of bilirubin, an endogenous antioxidant, have been associated with reduced risk of ischaemic heart disease (IHD) and myocardial infarction (MI). Whether this is a causal relationship remains unclear.......Elevated plasma levels of bilirubin, an endogenous antioxidant, have been associated with reduced risk of ischaemic heart disease (IHD) and myocardial infarction (MI). Whether this is a causal relationship remains unclear....

False high level in total bilirubin estimation in nonicteric serum

African Journals Online (AJOL)

estimation of total bilirubin by DiaSys and Randox reagents along with simultaneous re-estimation by Roche reagents in ... been used mainly due to slightly lower cost in ... MATERIALS AND METHODS ... air-conditioned laboratory overnight. ..... Elevated IgG causing spurious elevation in serum total bilirubin assay. Asia.

A Comparison between Transcutaneous and Total Serum Bilirubin in Healthy-term Greek Neonates with Clinical Jaundice

Directory of Open Access Journals (Sweden)

Charalambos Neocleous

2014-01-01

Full Text Available The accuracy of transcutaneous bilirubin meters has been assessed in newborns from various ethnic backgrounds. However, there are limited data on Greek newborns. Our study examined the accuracy of transcutaneous bilirubin measurements in clinically jaundiced healthy-term Greek newborns, using total serum bilirubin as the reference standard, in order to re-evaluate our local guidelines about neonatal jaundice. Clinically jaundiced newborns requiring total serum bilirubin level estimation were recruited prospectively. 368 pairs of total serum bilirubin/transcutaneous bilirubin measurements were taken in 222 newborns, using a direct spectrophotometric device and the BiliCheck device, respectively. The level of agreement between the obtained transcutaneous bilirubin and total serum bilirubin values was assessed. Our data were analysed using the Stata/SE 12.0 (StataCorp LP, USA statistical programme. The mean (± SD TSB was 225.4 ± 25.4 μmol/l and the mean (± SD TcB was 237.9 ± 21.0 μmol/l. The correlation between the values was poor (Pearson’s correlation coefficient 0.439; Lin’s concordance coefficient 0.377 [95% CI 0.301 to 0.453]; P<0.001. The Bland-Altman analysis demonstrated that transcutaneous bilirubin measurements tended to overestimate the total serum bilirubin value (mean difference 12.5 ± 24.9 μmol/l, with wide 95% limits of agreement (–36.2 μmol/l to 61.3 μmol/l. Transcutaneous bilirubin values did not correlate well with total serum bilirubin values, being often imprecise in predicting the actual total serum bilirubin levels. This permits us to continue estimating total serum bilirubin in clinically jaundiced newborns according to our local guidelines, in order to safely decide the appropriate care plan.

Effect of bilirubin on the spectrophotometric and radionuclide assay for serum angiotensin-converting enzyme

International Nuclear Information System (INIS)

Saxe, A.W.; Hollinger, M.A.; Essam, T.

1986-01-01

The effect of bilirubin on serum angiotensin-converting enzyme (ACE) activity was studied with spectrophotometric and radionuclide assays. In the spectrophotometric assay addition of bilirubin to normal serum from dog, mouse, and human produced a dose-related inhibition of ACE activity. A 50% decrease in human ACE activity was produced by the addition of approximately 250 mg/L in vitro. Serum from icteric patients with elevated bilirubin was also associated with a reduction in ACE activity in the spectrophotometric assay. A 50% decrease in ACE activity in these samples was associated with a serum bilirubin of approximately 220 mg/L. In the radionuclide assay, however, addition of bilirubin to normal human serum failed to reduce measured ACE activity. The use of a radionuclide assay for serum ACE in clinical samples offers the advantage of less interference from serum bilirubin

Albumin-Bilirubin and Platelet-Albumin-Bilirubin Grades Accurately Predict Overall Survival in High-Risk Patients Undergoing Conventional Transarterial Chemoembolization for Hepatocellular Carcinoma.

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Hansmann, Jan; Evers, Maximilian J; Bui, James T; Lokken, R Peter; Lipnik, Andrew J; Gaba, Ron C; Ray, Charles E

2017-09-01

To evaluate albumin-bilirubin (ALBI) and platelet-albumin-bilirubin (PALBI) grades in predicting overall survival in high-risk patients undergoing conventional transarterial chemoembolization for hepatocellular carcinoma (HCC). This single-center retrospective study included 180 high-risk patients (142 men, 59 y ± 9) between April 2007 and January 2015. Patients were considered high-risk based on laboratory abnormalities before the procedure (bilirubin > 2.0 mg/dL, albumin 1.2 mg/dL); presence of ascites, encephalopathy, portal vein thrombus, or transjugular intrahepatic portosystemic shunt; or Model for End-Stage Liver Disease score > 15. Serum albumin, bilirubin, and platelet values were used to determine ALBI and PALBI grades. Overall survival was stratified by ALBI and PALBI grades with substratification by Child-Pugh class (CPC) and Barcelona Liver Clinic Cancer (BCLC) stage using Kaplan-Meier analysis. C-index was used to determine discriminatory ability and survival prediction accuracy. Median survival for 79 ALBI grade 2 patients and 101 ALBI grade 3 patients was 20.3 and 10.7 months, respectively (P  .05). ALBI and PALBI grades are accurate survival metrics in high-risk patients undergoing conventional transarterial chemoembolization for HCC. Use of these scores allows for more refined survival stratification within CPC and BCLC stage. Copyright © 2017 SIR. Published by Elsevier Inc. All rights reserved.

The inverse association of incident cardiovascular disease with plasma bilirubin is unaffected by adiponectin

NARCIS (Netherlands)

Dullaart, Robin P. F.; Boersema, Jeltje; Lefrandt, Joop D.; Wolffenbuttel, Bruce H. R.; Bakker, Stephan J. L.

Objective: Bilirubin may protect against atherosclerotic cardiovascular disease (CVD). The heme oxygenase pathway is crucial for bilirubin generation, and is stimulated by adiponectin. We tested the relationship of plasma bilirubin with adiponectin, and determined whether the association of incident

Bilirubin metabolism in the spiny dogfish, Squalus acanthias, and the small skate, Raja erinacea

NARCIS (Netherlands)

Jansen, P. L.; Arias, I. M.

1977-01-01

1. The main bilirubin conjugate in bile of spiny dogfish (Squalus Acanthias) and small skate (Raja Erinacea) is bilirubin monoglucuronide. 2. Microsomal preparations from dogfish and small skate liver have similar bilirubin UDPglucuronyltransferase (UDPGT) activity and catalyze the conjugation of

Prognostic impact of serum bilirubin level on long-term renal survival in IgA nephropathy.

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Tanaka, Shigeru; Ninomiya, Toshiharu; Masutani, Kosuke; Nagata, Masaharu; Tsuchimoto, Akihiro; Tsuruya, Kazuhiko; Kitazono, Takanari

2015-12-01

Serum bilirubin has been recognized as a novel endogenous antioxidant. The aim of our study was to evaluate the impact of serum bilirubin on kidney prognosis in IgA nephropathy (IgAN). We followed retrospectively 694 patients with IgAN diagnosed by renal biopsy between 1982 and 2010. The risk factors for developing end-stage renal disease (ESRD) were estimated using a Cox proportional hazard model. Predictive performance between models with or without serum bilirubin was evaluated by calculating the net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Seventy-seven patients developed ESRD during the median 4.9 years of follow-up. Estimated glomerular filtration rate, proteinuria and histological severity were inversely related to bilirubin levels. In multivariate analysis, serum bilirubin was an independent risk factor for ESRD (hazard ratio for every 0.1 mg/dL decrease in serum bilirubin, 1.18; 95 % CI, 1.04-1.33). The incidence rate of ESRD decreased linearly with the increases in bilirubin levels (P for trend bilirubin was incorporated into a model with conventional ESRD risk factors, the NRI and IDI were 0.281 (P = 0.02) and 0.019 (P = 0.01), respectively. We demonstrated that lower bilirubin levels were significantly associated with higher risk of ESRD in IgAN. In addition, bilirubin provided incremental predictive value in the risk assessment for progression of IgAN beyond that provided by standard risk factors.

The Relation of Serum Bilirubin Level With Coronary Artery Disease Based on Angiographic Findings

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Taban Sadeghi Mohammadreza

2015-10-01

Full Text Available Objective: Lipid oxidation and generation of free radicals are important factors contributing to the formation of atherosclerotic plaque. Bilirubin is supposed to play a protective role against atherosclerosis, coronary artery diseases (CAD and inflammation for its strong antioxidant property. Thus, this study aims at investigating the relationship of bilirubin level with the severity and type of coronary artery stenosis (CAS in different patient groups. Materials and Methods: In this cross-sectional study 200 consecutive patients, who underwent elective angiography in Madani Heart hospital, Tabriz, Iran, were selected and their blood samples were measured for total, direct, and indirect bilirubin level, with Diazo method using colorimetric technique. Following angiography, comparisons were made between the severity and location of CAS and therapeutic follow-up plan with total, direct, and indirect bilirubin level. Results: Of 200 studied patients, 129 (64.5% and 71 (35.5% subjects were male and female, respectively. The cases were classified into 5 subgroups based on angiography results as follows: 59 (29.5% cases with normal angiography, 11 cases (5.5% with minimal CAD, 56 cases (28% with single vessel involvement, 35 (17.5% cases with two vessel involvement and 39 cases (19.5% with three vessel involvement. The mean total bilirubin level was 1.47 ± 0.8 mg/dl, 1.27 ± 0.12 mg/dl, 1.27 ± 0.06 mg/dl, 1.6 ± 0.04 mg/dl and 0.98 ± 0.05 mg/dl, respectively for the cases with above order. The mean difference in serum total bilirubin between normal angiography group and three-vessel involvement group was 0.49 mg/dl (P < .0001. There was a significant inverse relation between bilirubin level (total, direct and indirect and number of involved vessels and involvement intensity increased as serum bilirubin level decreased. Severity of coronary arteries stenosis as well as the number of involved vessels increased as serum bilirubin level decreased

Bilirubin glucuronidation revisited: proper assay conditions to estimate enzyme kinetics with recombinant UGT1A1.

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Zhou, Jin; Tracy, Timothy S; Remmel, Rory P

2010-11-01

Bilirubin, an end product of heme catabolism, is primarily eliminated via glucuronic acid conjugation by UGT1A1. Impaired bilirubin conjugation, caused by inhibition of UGT1A1, can result in clinical consequences, including jaundice and kernicterus. Thus, evaluation of the ability of new drug candidates to inhibit UGT1A1-catalyzed bilirubin glucuronidation in vitro has become common practice. However, the instability of bilirubin and its glucuronides presents substantial technical challenges to conduct in vitro bilirubin glucuronidation assays. Furthermore, because bilirubin can be diglucuronidated through a sequential reaction, establishment of initial rate conditions can be problematic. To address these issues, a robust high-performance liquid chromatography assay to measure both bilirubin mono- and diglucuronide conjugates was developed, and the incubation conditions for bilirubin glucuronidation by human embryonic kidney 293-expressed UGT1A1 were carefully characterized. Our results indicated that bilirubin glucuronidation should be assessed at very low protein concentrations (0.05 mg/ml protein) and over a short incubation time (5 min) to assure initial rate conditions. Under these conditions, bilirubin total glucuronide formation exhibited a hyperbolic (Michaelis-Menten) kinetic profile with a K(m) of ∼0.2 μM. In addition, under these initial rate conditions, the relative proportions between the total monoglucuronide and the diglucuronide product were constant across the range of bilirubin concentration evaluated (0.05-2 μM), with the monoglucuronide being the predominant species (∼70%). In conclusion, establishment of appropriate incubation conditions (i.e., very low protein concentrations and short incubation times) is necessary to properly characterize the kinetics of bilirubin glucuronidation in a recombinant UGT1A1 system.

Relationship between red blood cell distribution width, bilirubin, and clinical characteristics of patients with gastric cancer.

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Wei, T-T; Wang, L-L; Yin, J-R; Liu, Y-T; Qin, B-D; Li, J-Y; Yin, X; Zhou, L; Zhong, R-Q

2017-10-01

Red blood cell distribution width (RDW) and bilirubin have been proved to be prognostic factors for various types of cancer. However, their prognostic value in patients with gastric cancer (GC) remains largely unknown. To verify whether RDW and bilirubin are prognostic factors for patients with GC, we performed a cross-sectional study to analyze the relationship between RDW, bilirubin, and the clinical characteristics of patients with GC. Medical records of all newly diagnosed and pathologically proved patients with GC admitted to Changzheng Hospital between January 2016 and July 2016 were retrospectively reviewed. The relationship between RDW, bilirubin, and the clinical characteristics of patients with GC was analyzed. A total of 144 patients with GC were enrolled. Patients with GC had significantly higher RDW than healthy controls, even after adjusting for hemoglobin, while total bilirubin (TBIL), direct bilirubin (DBIL) and indirect bilirubin (IBIL) were significantly decreased. Furthermore, RDW and bilirubin were significantly correlated with tumor stage, as well as carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9). Our study indicated that RDW and bilirubin could be potential prognostic factors for patients of GC. © 2017 John Wiley & Sons Ltd.

Increased conjugated bilirubin is sufficient to initiate screening for biliary atresia

DEFF Research Database (Denmark)

Madsen, Stine Skipper; Kvist, Nina; Thorup, Jørgen

2015-01-01

INTRODUCTION: Biliary atresia is the leading cause of liver transplantation in children. It affects 1:15,000 in Denmark. With a national birth rate of 60,000, four children are born every year with biliary atresia. Early correction of biliary obstruction is essential to prevent fatal biliary...... cirrhosis. The Danish Health and Medicines Authority (DHMA) demands diagnostic evaluation of children with elevated level of serum bilirubin after two weeks of age. Biliary atresia has to be excluded if conjugated bilirubin level is above than 20 μmol/l, and/or more than 20% of total bilirubin...

Higher direct bilirubin levels during mid-pregnancy are associated with lower risk of gestational diabetes mellitus.

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Liu, Chaoqun; Zhong, Chunrong; Zhou, Xuezhen; Chen, Renjuan; Wu, Jiangyue; Wang, Weiye; Li, Xiating; Ding, Huisi; Guo, Yanfang; Gao, Qin; Hu, Xingwen; Xiong, Guoping; Yang, Xuefeng; Hao, Liping; Xiao, Mei; Yang, Nianhong

2017-01-01

Bilirubin concentrations have been recently reported to be negatively associated with type 2 diabetes mellitus. We examined the association between bilirubin concentrations and gestational diabetes mellitus. In a prospective cohort study, 2969 pregnant women were recruited prior to 16 weeks of gestation and were followed up until delivery. The value of bilirubin was tested and oral glucose tolerance test was conducted to screen gestational diabetes mellitus. The relationship between serum bilirubin concentration and gestational weeks was studied by two-piecewise linear regression. A subsample of 1135 participants with serum bilirubin test during 16-18 weeks gestation was conducted to research the association between serum bilirubin levels and risk of gestational diabetes mellitus by logistic regression. Gestational diabetes mellitus developed in 8.5 % of the participants (223 of 2969). Two-piecewise linear regression analyses demonstrated that the levels of bilirubin decreased with gestational week up to the turning point 23 and after that point, levels of bilirubin were increased slightly. In multiple logistic regression analysis, the relative risk of developing gestational diabetes mellitus was lower in the highest tertile of direct bilirubin than that in the lowest tertile (RR 0.60; 95 % CI, 0.35-0.89). The results suggested that women with higher serum direct bilirubin levels during the second trimester of pregnancy have lower risk for development of gestational diabetes mellitus.

Serum bilirubin levels are inversely associated with PAI-1 and fibrinogen in Korean subjects.

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Cho, Hyun Sun; Lee, Sung Won; Kim, Eun Sook; Shin, Juyoung; Moon, Sung Dae; Han, Je Ho; Cha, Bong Yun

2016-01-01

Oxidative stress may contribute to atherosclerosis and increased activation of the coagulation pathway. Bilirubin may reduce activation of the hemostatic system to inhibit oxidative stress, which would explain its cardioprotective properties shown in many epidemiological studies. This study investigated the association of serum bilirubin with fibrinogen and plasminogen activator inhibitor-1 (PAI-1), respectively. A cross-sectional analysis was performed on 968 subjects (mean age, 56.0 ± 11.2 years; 61.1% men) undergoing a general health checkup. Serum biochemistry was analyzed including bilirubin subtypes, insulin resistance (using homeostasis model of assessment [HOMA]), C-reactive protein (CRP), fibrinogen, and PAI-1. Compared with subjects with a total bilirubin (TB) concentration of 17.1 μmol/L had a smaller waist circumference, a lower triglyceride level, a lower prevalence of metabolic syndrome, and decreased HOMA-IR and CRP levels. Correlation analysis revealed linear relationships of fibrinogen with TB and direct bilirubin (DB), whereas PAI-1 was correlated with DB. After adjustment for confounding factors, bilirubin levels were inversely associated with fibrinogen and PAI-1 levels, respectively. Multivariate regression models showed a negative linear relationship between all types of bilirubin and fibrinogen, whereas there was a significant linear relationship between PAI-1 and DB. High bilirubin concentrations were independently associated with low levels of fibrinogen and PAI-1, respectively. The association between TB and PAI-1 was confined to the highest TB concentration category whereas DB showed a linear association with PAI-1. Bilirubin may protect against the development of atherothrombosis by reducing the hemostatic response. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

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

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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. Copyright © 2015 Elsevier Inc. All rights reserved.

Highly Sensitive and Selective Sensing of Free Bilirubin Using Metal-Organic Frameworks-Based Energy Transfer Process.

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Du, Yaran; Li, Xiqian; Lv, Xueju; Jia, Qiong

2017-09-13

Free bilirubin, a key biomarker for jaundice, was detected with a newly designed fluorescent postsynthetically modified metal organic framework (MOF) (UIO-66-PSM) sensor. UiO-66-PSM was prepared based on the aldimine condensation reaction of UiO-66-NH 2 with 2,3,4-trihydroxybenzaldehyde. The fluorescence of UIO-66-PSM could be effectively quenched by free bilirubin via a fluorescent resonant energy transfer process, thus achieving its recognition of free bilirubin. It was the first attempt to design a MOF-based fluorescent probe for sensing free bilirubin. The probe exhibited fast response time, low detection limit, wide linear range, and high selectivity toward free bilirubin. The sensing system enabled the monitor of free bilirubin in real human serum. Hence, the reported free bilirubin sensing platform has potential applications for clinical diagnosis of jaundice.

Transport and metabolism at blood-brain interfaces and in neural cells: relevance to bilirubin-induced encephalopathy

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Silvia eGazzin

2012-05-01

Full Text Available Bilirubin, the end-product of heme catabolism, circulates in non pathological plasma mostly as a protein-bound species. When bilirubin concentration builds up, the free fraction of the molecule increases. Unbound bilirubin then diffuses across blood-brain interfaces into the brain, where it accumulates and exerts neurotoxic effects. In this classical view of bilirubin neurotoxicity, blood-brain interfaces act merely as structural barriers impeding the penetration of the pigment-bound carrier protein, and neural cells are considered as passive targets of its toxicity. Yet, the role of blood-brain interfaces in the occurrence of bilirubin encephalopathy appears more complex than being simple barriers to the diffusion of bilirubin, and neural cells such as astrocytes and neurons can play an active role in controlling the balance between the neuroprotective and neurotoxic effects of bilirubin. This article reviews the emerging in vivo and in vitro data showing that transport and metabolic detoxification mechanisms at the blood-brain and blood-CSF barriers may modulate bilirubin flux across both cellular interfaces, and that these protective functions can be affected in chronic hyperbilirubinemia. Then the in vivo and in vitro arguments in favor of the physiological antioxidant function of intracerebral bilirubin are presented, as well as with the potential role of transporters such as ABCC-1 and metabolizing enzymes such as cytochromes P-450 in setting the cerebral cell- and structure-specific toxicity of bilirubin following hyperbilirubinemia. The relevance of these data to the pathophysiology of bilirubin-induced neurological diseases is discussed.

Constitutive androstane receptor activation promotes bilirubin clearance in a murine model of alcoholic liver disease.

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Wang, Xiuyan; Zheng, Liyu; Wu, Jinming; Tang, Binbin; Zhang, Mengqin; Zhu, Debin; Lin, Xianfan

2017-06-01

Increased plasma levels of bilirubin have been reported in rat models and patients with alcoholic liver disease (ALD). The constitutive androstane receptor (CAR) is a known xenobiotic receptor, which induces the detoxification and transport of bilirubin. In the present study, the bilirubin transport regulatory mechanisms, and the role of CAR activation in hepatic and extrahepatic bilirubin clearance were investigated in a murine model of ALD. The mice were fed a Lieber-DeCarli ethanol diet or an isocaloric control diet for 4 weeks, followed by the administration of CAR agonists, 1,4-bis-[2‑(3,5-dichlorpyridyloxy)]benzene (TCPOBOP) and phenobarbital (PB), and their vehicles to examine the effect of the pharmacological activation of CAR on serum levels of bilirubin and on the bilirubin clearance pathway in ALD by serological survey, western blotting and reverse transcription‑quantitative polymerase chain reaction. The results showed that chronic ethanol ingestion impaired the nuclear translocation of CAR, which was accompanied by elevated serum levels of bilirubin, suppression of the expression of hepatic and renal organic anion transporting polypeptide (OATP) 1A1 and hepatic multidrug resistance‑associated protein 2 (MRP2), and induction of the expression of UDP-glucuronosyltransferase (UGT) 1A1. The activation of CAR by TCPOBOP and PB resulted in downregulation of the serum levels of bilirubin followed by selective upregulation of the expression levels of OATP1A1, OATP1A4, UGT1A1 and MRP2 in ALD. These results revealed the bilirubin transport regulatory mechanisms and highlighted the importance of CAR in modulating the bilirubin clearance pathway in the ALD mouse model.

Serum bilirubin: a simple routine surrogate marker of the progression of chronic kidney disease.

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Moolchandani, K; Priyadarssini, M; Rajappa, M; Parameswaran, S; Revathy, G

2016-10-01

Studies suggest that Chronic Kidney Disease (CKD) is a global burden health associated with significant comorbid conditions. Few biochemical parameters have gained significance in predicting the disease progression. The present work aimed to study the association of the simple biochemical parameter of serum bilirubin level with the estimated glomerular filtration rate (eGFR), and to assess their association with the co-morbid conditions in CKD. We recruited 188 patients with CKD who attended a Nephrology out-patient department. eGFR values were calculated based on the serum creatinine levels using CKD-EPI formula. Various biochemical parameters including glucose, creatinine, uric acid, total and direct bilirubin were assayed in all study subjects. Study subjects were categorized into subgroups based on their eGFR values and their diabetic status and the parameters were compared among the different subgroups. We observed a significantly decreased serum bilirubin levels (p bilirubin levels (r = 0.92). We also observed a significant positive correlation between the eGFR levels and the direct bilirubin levels (r = 0.76). On multivariate linear regression analysis, we found that total and direct bilirubin independently predict eGFR, after adjusting for potential confounders (p bilirubin may help in predicting the early progression of CKD and more so in diabetic CKD.

Magnetic polymer-silica composites as bioluminescent sensors for bilirubin detection

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Timin, Alexander S., E-mail: a_timin@mail.ru [Inorganic Chemistry Department, Ivanovo State University of Chemistry and Technology (ISUCT), 7, Sheremetevsky prosp., 153000, Ivanovo (Russian Federation); RASA Center in Tomsk, Tomsk Polytechnic University, pros. Lenina, 30, Tomsk (Russian Federation); Solomonov, Alexey V. [Inorganic Chemistry Department, Ivanovo State University of Chemistry and Technology (ISUCT), 7, Sheremetevsky prosp., 153000, Ivanovo (Russian Federation); Department of Materials and Interfaces, Weizmann Institute of Science, Rehovot, 7610001 (Israel); Kumagai, Akiko; Miyawaki, Atsushi [Cell Function Dynamics, Brain Science Institute RIKEN, 2-1 Hirosawa, Wako-city, Saitama, 351-0198 (Japan); Khashirova, Svetlana Yu; Zhansitov, Azamat [Kabardino-Balkar State University, 173 Chernyshevskogo St., Nal' chik, 360004, Kabardino-Balkaria (Russian Federation); Rumyantsev, Evgeniy V. [Inorganic Chemistry Department, Ivanovo State University of Chemistry and Technology (ISUCT), 7, Sheremetevsky prosp., 153000, Ivanovo (Russian Federation)

2016-11-01

The synthesis of multifunctional nano-sized materials is leading to the rapid development of key application, including improved drug delivery, bioimaging and protein separation. In this work, magnetic silica particles modified with novel guanidine containing co-polymers were manufactured via sol-gel method. To evaluate the chemical composition of our prepared samples, FT-IR spectroscopy and thermogravimetry were conducted. Scanning electron microscopy was used in order to investigate the morphology of final products after modification by guanidine containing co-polymers and iron nanoparticles. In addition, the surface of polymer-silica composites was functionalized by the novel bilirubin-inducible fluorescent protein UnaG. In an aqueous bilirubin solution, the silica particles decorated with the polymer-UnaG have showed bright fluorescence. Synthesis and characterization of these hybrid materials allow developing of new multifunctional nano-sized materials, which will be used for detection and separation of bilirubin, a lipophilic heme catabolite that is a clinical diagnostic for liver function. - Highlights: • Novel magnetic silicas grafted by guanidine containing co-polymers were prepared. • Unag protein was effectively loaded into polymer coated silicas. • The fluorescent properties depend on content of bilirubin.

Magnetic polymer-silica composites as bioluminescent sensors for bilirubin detection

International Nuclear Information System (INIS)

Timin, Alexander S.; Solomonov, Alexey V.; Kumagai, Akiko; Miyawaki, Atsushi; Khashirova, Svetlana Yu; Zhansitov, Azamat; Rumyantsev, Evgeniy V.

2016-01-01

The synthesis of multifunctional nano-sized materials is leading to the rapid development of key application, including improved drug delivery, bioimaging and protein separation. In this work, magnetic silica particles modified with novel guanidine containing co-polymers were manufactured via sol-gel method. To evaluate the chemical composition of our prepared samples, FT-IR spectroscopy and thermogravimetry were conducted. Scanning electron microscopy was used in order to investigate the morphology of final products after modification by guanidine containing co-polymers and iron nanoparticles. In addition, the surface of polymer-silica composites was functionalized by the novel bilirubin-inducible fluorescent protein UnaG. In an aqueous bilirubin solution, the silica particles decorated with the polymer-UnaG have showed bright fluorescence. Synthesis and characterization of these hybrid materials allow developing of new multifunctional nano-sized materials, which will be used for detection and separation of bilirubin, a lipophilic heme catabolite that is a clinical diagnostic for liver function. - Highlights: • Novel magnetic silicas grafted by guanidine containing co-polymers were prepared. • Unag protein was effectively loaded into polymer coated silicas. • The fluorescent properties depend on content of bilirubin.

Hepatic bilirubin uptake in the isolated perfused rat liver is not facilitated by albumin binding

International Nuclear Information System (INIS)

Stollman, Y.R.; Gaertner, U.; Theilmann, L.; Ohmi, N.; Wolkoff, A.W.

1983-01-01

Bilirubin uptake by the liver has kinetic characteristics which suggest carrier-mediation. Bilirubin is readily bound to albumin. A liver cell surface receptor for albumin has been postulated. The present study was designed to examine directly whether albumin facilitates the hepatic uptake of bilirubin and whether uptake of bilirubin depends on binding to albumin. Rat liver was perfused with a protein-free fluorocarbon medium, and single-pass uptake of 1, 10, or 200 nmol of [ 3 H]bilirubin was determined after injection as an equimolar complex with 125 I-albumin, with 125 I-ligandin, or free with only a [ 14 C]sucrose reference. Uptake of 10 nmol of [ 3 H]bilirubin was 67.5 +/- 3.7% of the dose when injected with 125 I-albumin, 67.4 +/- 6.5% when injected with 125 I-ligandin, and 74.9 +/- 2.4% when injected with [ 14 C]sucrose (P greater than 0.1). At 200 nmol, uptake fell to 46.4 +/- 3.1% ( 125 I-albumin) and 63.3 +/- 3.4% [( 14 C]sucrose) of injected [ 3 H]bilirubin (P less than 0.01), which suggests saturation of the uptake mechanism. When influx was quantitated by the model of Goresky, similar results were obtained. When [ 3 H]bilirubin was injected simultaneously with equimolar 125 I-albumin and a [ 14 C]sucrose reference, there was no delay in 125 I-albumin transit as compared with that of [ 14 C]sucrose. This suggested that the off-rate of albumin from a putative hepatocyte receptor would have to be very rapid, which is unusual for high affinity receptor-ligand interaction. There was no evidence for facilitation of bilirubin uptake by binding to albumin or for interaction of albumin with a liver cell surface receptor. These results suggest that the hepatic bilirubin uptake mechanism is one of high affinity which can extract bilirubin from circulating carriers such as albumin, ligandin, or fluorocarbon

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

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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.

Point Spectroscopy System for Noncontact and Noninvasive Prediction of Transcutaneous Bilirubin Concentration

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Ong, P. E.; K. C Huong, Audrey

2017-08-01

This paper presents the use of a point spectroscopy system to determine one’s transcutaneous bilirubin level using Modified Lambert Beer model and the developed fitting routine. This technique required a priori knowledge of extinction coefficient of bilirubin and hemoglobin components in the wavelength range of 440-500 nm for the prediction of the required parameter value. This work was conducted on different skin sites of six healthy Asians namely on the thenar region of the palm of their hand, back of the hand, posterior and anterior forearm. The obtained results revealed the lowest mean transcutaneous bilirubin concentration of 0.44±0.3 g/l predicted for palm site while the highest bilirubin level of 0.98±0.2 g/l was estimated for posterior forearm. These values were also compared with that presented in the literature. This study found considerably good consistency in the value predicted for different subjects especially at the thenar region of the palm. This work concluded that the proposed system and technique may be suitably served as an alternative means to noncontact and noninvasive measurement of one’s transcutaneous bilirubin level at palm site.

Serum bilirubin levels are positively associated with glycemic variability in women with type 2 diabetes.

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Kim, Lee Kyung; Roh, Eun; Kim, Min Joo; Kim, Min Kyeong; Park, Kyeong Seon; Kwak, Soo Heon; Cho, Young Min; Park, Kyong Soo; Jang, Hak Chul; Jung, Hye Seung

2016-11-01

Glycemic variability is known to induce oxidative stress. We investigated the relationships between glycemic variability and serum bilirubin levels, an endogenous anti-oxidant, in patients with diabetes. A cross-sectional study was carried out with 77 patients with type 2 diabetes who had been recruited to two clinical studies from 2008 to 2014. There were no participants with diseases of the pancreas, liver, biliary tract and chronic renal insufficiency. Glycemic variation was calculated by a continuous glucose monitoring system, and correlation analyses were carried out to evaluate their association with bilirubin levels. Multiple linear regression was carried out to identify independent factors influencing bilirubin levels and glycemic variation. Among the participants, 42.3% were men. The mean (standard deviation) age was 61.5 years (10.4 years), body mass index was 24.2 kg/m 2 (2.8 kg/m 2 ), diabetes duration was 17.7 years (9.5 years), hemoglobin A 1c was 60.7 mmol/mol (7.1 mmol/mol; 7.7 [0.7]%) and bilirubin was 11.8 μmol/L (4.10 μmol/L). Serum bilirubin levels were not different according to age, body mass index and hemoglobin A 1c . However, the mean amplitude of glucose excursion was positively associated with bilirubin levels in women (r = 0.588, P bilirubin and mean amplitude of glucose excursion remained significant (r = 0.566, P bilirubin was an independent determinant for the mean amplitude of glucose excursion in women. 1,5-Anhydroglucitol was also associated with bilirubin levels in women. Bilirubin level within the physiological range might be an independent predictor for glycemic variability in women with type 2 diabetes. © 2016 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

Amine-functionalized PVA-co-PE nanofibrous membrane as affinity membrane with high adsorption capacity for bilirubin.

Science.gov (United States)

Wang, Wenwen; Zhang, Hao; Zhang, Zhifeng; Luo, Mengying; Wang, Yuedan; Liu, Qiongzhen; Chen, Yuanli; Li, Mufang; Wang, Dong

2017-02-01

In this study, poly(vinyl alcohol-co-ethylene) (PVA-co-PE) nanofibrous membrane was activated by sodium hydroxide and cyanuric chloride, and then the activated membranes were functionalized by 1,3-propanediamine, hexamethylenediamine and diethylenetriamine to be affinity membranes for bilirubin removal, respectively. The chemical structures and morphologies of membranes were investigated by SEM, FTIR and XPS. And the adsorption ability of different amine-functionalized nanofibrous membranes for bilirubin was characterized. Furthermore, the effects of temperature, initial concentration of bilirubin, NaCl concentration and BSA concentration on the adsorption capacity for bilirubin of diethylenetriamine-functionalized nanofibrous membrane were studied. Results indicated that the adsorption capacity for bilirubin of diethylenetriamine-functionalized nanofibrous membrane could reach 85mg/g membrane when the initial bilirubin concentration was 200mg/L while the adsorption capacity could be increased to 110mg/g membrane if the initial bilirubin concentration was more than 400mg/L. The dynamic adsorption of diethylenetriamine-functionalized nanofibrous membrane showed that the ligands of amine groups on the membrane surface could be used as far as possible by recirculating the plasma with certain flow rates. Therefore, the diethylenetriamine-functionalized PVA-co-PE nanofibrous membrane possessed high adsorption capacity for bilirubin and it can be candidate as affinity membrane for bilirubin removal. Copyright © 2016. Published by Elsevier B.V.

A Novel Newborn Rat Kernicterus Model Created by Injecting a Bilirubin Solution into the Cisterna Magna

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Song, Sijie; Hu, Ying; Gu, Xianfang; Si, Feifei; Hua, Ziyu

2014-01-01

Background Kernicterus still occurs around the world; however, the mechanism of bilirubin neurotoxicity remains unclear, and effective treatment strategies are lacking. To solve these problems, several kernicterus (or acute bilirubin encephalopathy) animal models have been established, but these models are difficult and expensive. Therefore, the present study was performed to establish a novel kernicterus model that is simple and affordable by injecting unconjugated bilirubin solution into the cisterna magna (CM) of ordinary newborn Sprague-Dawley (SD) rats. Methods On postnatal day 5, SD rat pups were randomly divided into bilirubin and control groups. Then, either bilirubin solution or ddH2O (pH = 8.5) was injected into the CM at 10 µg/g (bodyweight). For model characterization, neurobehavioral outcomes were observed, mortality was calculated, and bodyweight was recorded after bilirubin injection and weaning. Apoptosis in the hippocampus was detected by H&E staining, TUNEL, flow cytometry and Western blotting. When the rats were 28 days old, learning and memory ability were evaluated using the Morris water maze test. Results The bilirubin-treated rats showed apparently abnormal neurological manifestations, such as clenched fists, opisthotonos and torsion spasms. Bodyweight gain in the bilirubin-treated rats was significantly lower than that in the controls (Pbilirubin-treated rats were both dramatically higher than those of the controls (P = 0.004 and 0.017, respectively). Apoptosis and necrosis in the hippocampal nerve cells in the bilirubin-treated rats were observed. The bilirubin-treated rats performed worse than the controls on the Morris water maze test. Conclusion By injecting bilirubin into the CM, we successfully created a new kernicterus model using ordinary SD rats; the model mimics both the acute clinical manifestations and the chronic sequelae. In particular, CM injection is easy to perform; thus, more stable models for follow-up study are

Pulse radiolysis investigations on oxidation reactions of bilirubin in aqueous solutions (Preprint No. RC-3)

International Nuclear Information System (INIS)

Mohan, Hari; Gopinathan, C.

1988-02-01

The oxidation of bilirubin in aqueous solutions have been investigated by different oxidizing species such as CH 3 I.OH, Br 2 - and CO 3 - . The rate constant for the oxidation of bilirubin has been determined from the formation kinetics of bilirubin cations. (author). 3 refs

Imbalance between production and conjugation of bilirubin: a fundamental concept in the mechanism of neonatal jaundice.

Science.gov (United States)

Kaplan, Michael; Muraca, Maurizio; Hammerman, Cathy; Rubaltelli, Firmino F; Vilei, Maria T; Vreman, Hendrik J; Stevenson, David K

2002-10-01

The objective of this study was to evaluate the roles of production and conjugation of bilirubin, individually and in combination, in the mechanism of neonatal jaundice. A cohort of healthy, term male newborns was sampled on the third day of life, coincident with routine metabolic screening, for blood carboxyhemoglobin determination, a reflection of heme catabolism, and for serum unconjugated and conjugated bilirubin fractions, reflecting bilirubin conjugation. The former was determined by gas chromatography, corrected for inspired CO (COHbc), and expressed as percentage of total hemoglobin. Serum bilirubin fractions were quantified by alkaline methanolysis and reverse phase high performance liquid chromatography. The sum of all bilirubin fractions comprised serum total bilirubin (STB). Total conjugated bilirubin (TCB) was comprised of the sum of the conjugated fractions and was expressed as percentage of STB (TCB[%]). A "bilirubin production/conjugation index" (COHbc/[TCB(%)] represented the combined roles of these modalities in the mechanism of bilirubinemia. Relationships between STB concentrations on the one hand, and COHbc values, TCB(%) proportions, and the production/conjugation index on the other, were determined by applying a best-fit regression analysis methodology. Mean (+/- standard deviation) STB concentration at the time of sampling was 114 +/- 48 micro mol/L (range: 8-263 micro mol/L). Mean COHbc value was 0.77 +/- 0.19%, and median (interquartile range) TCB(%) was 0.737 (0.465-1.260)%. COHbc values correlated directly with STB concentrations (r = 0.38; s = 46.1), and TCB(%) correlated inversely with STB (r = 0.40; s = 45.8). The production/conjugation index correlated positively with STB values (r = 0.61; s = 45.8), the r value for the index being higher than that of either COHbc or TCB(%), individually. The bilirubin production/conjugation index seemed to have a biphasic relationship to STB: STB values rose steeply in concert with increasing index

Milk-borne epidermal growth factor modulates bilirubin levels in neonatal rats

Directory of Open Access Journals (Sweden)

Didem Cemile Yesilirmak

2015-11-01

Conclusion: Results suggest that EGF supplementation in newborn rats leads to a significant increase in intestinal mucosal proliferation and a significant decrease in bilirubin elimination. These data suggest that EGF possibly increases intestinal bilirubin absorption and may have a role in development of breast milk jaundice. Further studies are needed to confirm this hypothesis.

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

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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...

Clinical system model for monitoring the physiological status of jaundice by extracting bilirubin components from skin diffuse reflectance spectra

Science.gov (United States)

Kumar, Alla S.; Clark, Joseph; Beyette, Fred R., Jr.

2009-02-01

Neonatal jaundice is a medical condition which occurs in newborns as a result of an imbalance between the production and elimination of bilirubin. The excess bilirubin in the blood stream diffuses into the surrounding tissue leading to a yellowing of the skin. As the bilirubin levels rise in the blood stream, there is a continuous exchange between the extra vascular bilirubin and bilirubin in the blood stream. Exposure to phototherapy alters the concentration of bilirubin in the vascular and extra vascular regions by causing bilirubin in the skin layers to be broken down. Thus, the relative concentration of extra vascular bilirubin is reduced leading to a diffusion of bilirubin out of the vascular region. Diffuse reflectance spectra from human skin contains physiological and structural information of the skin and nearby tissue. A diffuse reflectance spectrum must be captured before and after blanching in order to isolate the intravascular and extra vascular bilirubin. A new mathematical model is proposed with extra vascular bilirubin concentration taken into consideration along with other optical parameters in defining the diffuse reflectance spectrum from human skin. A nonlinear optimization algorithm has been adopted to extract the optical properties (including bilirubin concentration) from the skin reflectance spectrum. The new system model and nonlinear algorithm have been combined to enable extraction of Bilirubin concentrations within an average error of 10%.

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

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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.

Bilirubin treatment suppresses pulmonary inflammation in a rat model of smoke-induced emphysema.

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Wei, Jingjing; Zhao, Hui; Fan, Guoquan; Li, Jianqiang

2015-09-18

Cigarette smoking is a significant risk factor for emphysema, which is characterized by airway inflammation and oxidative damage. To assess the capacity of bilirubin to protect against smoke-induced emphysema. Smoking status and bilirubin levels were recorded in 58 patients with chronic obstructive pulmonary diseases (COPD) and 71 non-COPD participants. The impact of smoking on serum bilirubin levels and exogenous bilirubin (20 mg/kg/day) on pulmonary injury was assessed in a rat model of smoking-induced emphysema. At sacrifice lung histology, airway leukocyte accumulation and cytokine and chemokine levels in serum, bronchoalveolar lavage fluid (BALF) and lung were analyzed. Oxidative lipid damage and anti-oxidative components was assessed by measuring malondialdehyde, superoxide dismutase (SOD) activity and glutathione. Total serum bilirubin levels were lower in smokers with or without COPD than non-smoking patients without COPD (P pulmonary injury by suppressing inflammatory cell recruitment and pro-inflammatory cytokine secretion, increasing anti-inflammatory cytokine levels, and anti-oxidant SOD activity in a rat model of smoke-induced emphysema. Copyright © 2015. Published by Elsevier Inc.

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

Science.gov (United States)

2010-04-01

... levels of bilirubin (total and unbound) in the blood (serum) of newborn infants to aid in indicating the risk of bilirubin encephalopathy (kernicterus). (b) Classification. Class I. [54 FR 30206, July 19...

Serum bilirubin concentration is associated with eGFR and urinary albumin excretion in patients with type 1 diabetes mellitus.

Science.gov (United States)

Nishimura, Takeshi; Tanaka, Masami; Sekioka, Risa; Itoh, Hiroshi

2015-01-01

Although relationships of serum bilirubin concentration with estimated glomerular filtration rate (eGFR) and urinary albumin excretion (UAE) in patients with type 2 diabetes have been reported, whether such relationships exist in patients with type 1 diabetes is unknown. A total of 123 patients with type 1 diabetes were investigated in this cross-sectional study. The relationship between bilirubin (total and indirect) concentrations and log(UAE) as well as eGFR was examined by Pearson's correlation analyses. Multivariate regression analyses were used to assess the association of bilirubin (total and indirect) with eGFR as well as log(UAE). A positive correlation was found between serum bilirubin concentration and eGFR; total bilirubin (r=0.223, p=0.013), indirect bilirubin (r=0.244, p=0.007). A negative correlation was found between serum bilirubin concentration and log(UAE); total bilirubin (r=-0.258, p=0.005), indirect bilirubin (r=-0.271, p=0.003). Multivariate regression analyses showed that indirect bilirubin concentration was an independent determinant of eGFR and log(UAE). Bilirubin concentration is associated with both eGFR and log(UAE) in patients with type 1 diabetes. Bilirubin might have a protective role in the progression of type 1 diabetic nephropathy. Copyright © 2015 Elsevier Inc. All rights reserved.

Higher hydrocortisone dose increases bilirubin in hypopituitary patients- results from an RCT.

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Werumeus Buning, Jorien; Kootstra-Ros, Jenny E; Brummelman, Pauline; van den Berg, Gerrit; van der Klauw, Melanie; Wolffenbuttel, Bruce H R; van Beek, André P; Dullaart, Robin P F

2016-05-01

Bilirubin has anti-oxidative and anti-inflammatory properties, which may explain its proposed protective effects on the development of cardiometabolic disorders. Glucocorticoids affect heme oxygenase regulation in vitro, which plays a key role in bilirubin production. Effects of variations in glucocorticoid exposure on circulating bilirubin levels in humans are unknown. Here we tested whether a higher hydrocortisone replacement dose affects circulating bilirubin in hypopituitary patients. A randomized double-blind cross-over study (ClinicalTrials.gov, number NCT01546992) was performed in 47 patients with secondary adrenal failure [10-week exposure to a higher hydrocortisone dose (0·4-0·6 mg/kg body weight) vs. 10 weeks of a lower hydrocortisone dose (0·2-0·3 mg/kg body weight)]. Plasma total bilirubin was increased by 10% from 7 to 8 μM in response to the higher hydrocortisone dose (P = 0·033). This effect was inversely related to age (P = 0·042), but was unaffected by sex, obesity and (replacement for) other hormonal insufficiencies. The higher hydrocortisone dose also resulted in lower alkaline phosphatase (P = 0·006) and aspartate aminotransferase activities (P = 0·001). Bilirubin is modestly increased in response to higher glucocorticoid exposure in humans, in conjunction with lower alkaline phosphatase and aspartate aminotransferase activities, which are supposed to represent biomarkers of a pro-inflammatory state and enhanced liver fat accumulation. © 2016 The Authors. European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.

Multiple binding of bilirubin to human serum albumin and cobinding with laurate

DEFF Research Database (Denmark)

Sato, H; Honoré, B; Brodersen, R

1988-01-01

Numerical analysis of multiple binding of two ligands to one carrier has been accomplished, using the principle of several sets of acceptable binding constants, with bilirubin-laurate-albumin as an example. Binding of bilirubin to defatted human serum albumin was investigated by a spectroscopic...

Validation of a transcutaneous bilirubin meter in Mongolian neonates: comparison with total serum bilirubin.

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Akahira-Azuma, Moe; Yonemoto, Naohiro; Ganzorig, Battsengel; Mori, Rintaro; Hosokawa, Shinichi; Matsushita, Takeji; Bavuusuren, Bayasgalantai; Shonkhuuz, Enkhtur

2013-09-27

Neonatal hyperbilirubinemia, especially kernicterus, can be prevented by screening for neonatal jaundice. The transcutaneous bilirubin (TcB) meter is a non-invasive medical device for screening neonates. The study aimed to investigate the validity of a TcB meter in a resource-limited setting such as Mongolia. Term and late preterm neonates from the National Center for Maternal and Child Health of Ulaanbaatar in Mongolia who met the inclusion criteria (gestational age ≥35 weeks, birth weight ≥2000 g, postnatal age ≤ 1 month) were enrolled in the study. We used a TcB meter, JM-103 to screen for neonatal jaundice. TcB measurements at the infant's forehead and midsternum were performed within 3 h of obtaining samples for total serum bilirubin (TSB) measurement. We analyzed the correlation between TcB measurements and TSB measurements to validate the meter. A total of 47 term and six late preterm neonates were included in the study. TcB measured by the meter at both the forehead and the midsternum showed a strong correlation with TSB measured in the laboratory. The correlation equations were TSB = 1.409+0.8655 × TcB (R2=0.78871) at the forehead, and TSB = 0.7555+0.8974 × TcB (R2=0.78488) at the midsternum. Bland-Altman plots and the Bradley-Blackwood test showed no significant differences between the two methods at all measured ranges of bilirubin. The mean areas under the curves of TcB at the forehead and midsternum at three TSB levels (>10 mg/dL, >13 mg/dL, >15 mg/dL) of TcB were greater than 0.9, and all had high sensitivity and specificity. This study established the validity of the JM-103 meter as a screening tool for neonatal jaundice in term and late preterm infants in Mongolia. Future studies are needed, including the establishment of a TcB hour-specific nomogram, for more effective clinical practice to prevent severe hyperbilirubinemia.

Variation in the serum bilirubin levels in newborns according to gender and seasonal changes

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Jyoti Bala

2015-01-01

Full Text Available Introduction: Bilirubin is a substance that is produced during the process of hemolysis. Gender influences on neonatal illnesses and outcomes have remained a topic of debate and investigation. Empirical neonatological experience suggests that prevalence and degree of neonatal jaundice might be dependent on seasonal variation also. The aim of our study is to interpret the bilirubin levels in newborns according to gender and seasonal variation. Materials and Methods: The study was done from October 2012 to July of 2013 (differentiated by seasonal variation. A total of 1000 jaundiced newborn (500 of each sex diagnosed clinically and divided equally in summer and winter season were studied to assess the total, direct and indirect serum bilirubin levels using colorimetry. Results: Out of total 1676 deliveries (439 were caesarean, 13 were assisted and rest were normal during winter season and 1475 deliveries (399 were Cesarean, 14 were assisted and rest were normal during summer season, 500 male newborn and 500 female newborn were analysed, divided equally in both seasons. Serum bilirubin was higher in males in summers and mainly comprised unconjugated bilirubin while direct bilirubin was higher in females in winters. Raised indirect bilirubin was more common in males born in summer than those born in winters (P = 041. In winters raised direct bilirubin was more common in females as compared to males (P = 0.019. Among female neonates total and indirect bilirubin was significantly raised in those born in summers (P = < 0.001 and <0.001, respectively while direct was raised in those born in winters (P = 0.003. Conclusion: Physiological and pathologic phenomena associated with male gender must be integrated in the frame of understanding of both susceptibility and protection of the male newborn which has not been available for adequate investigation in the past. The higher temperature during the summer, with a greater influence of higher breastfeeding

First animal experiments and clinical investigations with sup(99m)Tc-bilirubin

International Nuclear Information System (INIS)

Schneider, G.; Kaempfer, I.; Blottner, A.; Rogos, R.; Deckart, H.

1986-01-01

Labelling of bilirubin with sup(99m)Tc is described. The distribution and elimination of the labelled substance was investigated in mice, rabbits, dogs and pigs. Within 5 minutes p.i. the labelled substance accumulated in the liver and was eliminated within several hours. Comparative studies of 14 C bilirubin and 14 C sup(99m)Tc bilirubin showed identical distribution patterns. Clinial trials were conducted in 60 patients who received 0.0015 mg/kg i.v. (total dose, 60-80 MBq of sup(99m)Tc bilirubin -> 1.6 - 2.2 mCi). Images were obtained in the first 20 min p.i. as well as after 2 and 24 hours. To determine the blood clearance blood samples were taken in the first hours and activity curves were recorded over the cardiac and temporal regions. As elimination from the liver was slow, gall bladder and bile duct imaging was not successful before 1 to 3 hours p.i. The severity of liver damage can be established on the basis of blood clearance, onset of active liver uptake, elimination from the liver and 24 hours excretion in percent. Labelled bilirubin is a suitable material for morphologic and dynamic functional imaging of the liver (e.g. for SPECT studies). Incidents were absent throughout. (Author)

Three-dimensionally porous graphene: A high-performance adsorbent for removal of albumin-bonded bilirubin.

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Ma, Chun Fang; Gao, Qiang; Xia, Kai Sheng; Huang, Zhi Yuan; Han, Bo; Zhou, Cheng Gang

2017-01-01

The development of bilirubin adsorbents with high adsorption efficiencies towards albumin-bonded bilirubin is still a considerable challenge. In this work, a three-dimensionally porous graphene (3D-pGR) has been fabricated through a simple carbon dioxide (CO 2 ) activation of thermally exfoliated graphite oxide (EGO). Intriguingly, the resultant 3D-pGR material showed hierarchically micro-meso-macroporous structure, high specific surface area of up to 843m 2 g -1 , and large pore volume as high as 2.71cm 3 g -1 . Besides, the large planar π-configuration structure of 3D-pGR made it possible to compete effectively with albumin for bilirubin binding. Taking advantages of these fantastic characteristics, the 3D-pGR was demonstrated to be extraordinarily efficient for bilirubin removal from a bovine serum albumin (BSA)-rich solution. Under optimized conditions, the maximum adsorption capacity of 3D-pGR for BSA-bonded bilirubin was up to 126.1mgg -1 , which is not only significantly higher than the adsorption capacities of currently available adsorbents towards albumin-bonded bilirubin, but also superior to those of many reported adsorbents towards free bilirubin. In addition, the hemolysis assay of 3D-pGR indicated that this material had negligible hemolysis effect. Findings from this study may open up important new possibilities for removal of protein-bonded toxins. Copyright © 2016 Elsevier B.V. All rights reserved.

Plasma malondialdehyde, bilirubin, homocysteine and total ...

African Journals Online (AJOL)

Oxidative stress has been implicated in coronary artery disease (CAD). Malondialdehyde (MDA) is lipid peroxidation end product. Bilirubin may act as an antioxidant that suppresses lipid oxidation. The role of MDA and antioxidant capacity and their inter-relationship in patients with and without CAD was investigated.

The correlation of serum bilirubin levels with disease activity in patients with rheumatoid arthritis.

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Peng, You-Fan; Wang, Jun-Li; Pan, Guo-Gang

2017-06-01

We investigated the relationship between serum bilirubin and disease activity in patients with rheumatoid arthritis (RA). We included a total of 173 consecutive RA patients without steroid treatment and 346 healthy subjects; the disease activity score in 28 joints (DAS28) was used to assess disease activity in patients with RA. Serum bilirubin concentrations were significantly lower in RA patients than in controls. Serum bilirubin was found to be negatively correlated with C-reactive protein (CRP) concentration and erythrocyte sedimentation rate (ESR) (r=-0.165, P=0.030; r=-192, P=0.012) in patients with RA. There was a negative correlation between the serum bilirubin and DAS28 score (r=-0.331, Pbilirubin was independently associated with the DAS28 score (b=-0.225, P=0.001) in the multiple linear regression analysis. Serum bilirubin concentrations are lower in patients with RA compared to controls and correlate with disease activity in patients with RA. Copyright © 2017. Published by Elsevier B.V.

Bilirubin Decreases Macrophage Cholesterol Efflux and ATP-Binding Cassette Transporter A1 Protein Expression.

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Wang, Dongdong; Tosevska, Anela; Heiß, Elke H; Ladurner, Angela; Mölzer, Christine; Wallner, Marlies; Bulmer, Andrew; Wagner, Karl-Heinz; Dirsch, Verena M; Atanasov, Atanas G

2017-04-28

Mild but chronically elevated circulating unconjugated bilirubin is associated with reduced total and low-density lipoprotein cholesterol concentration, which is associated with reduced cardiovascular disease risk. We aimed to investigate whether unconjugated bilirubin influences macrophage cholesterol efflux, as a potential mechanism for the altered circulating lipoprotein concentrations observed in hyperbilirubinemic individuals. Cholesterol efflux from THP-1 macrophages was assessed using plasma obtained from normo- and hyperbilirubinemic (Gilbert syndrome) humans (n=60 per group) or (heterozygote/homozygote Gunn) rats (n=20 per group) as an acceptor. Hyperbilirubinemic plasma from patients with Gilbert syndrome and Gunn rats induced significantly reduced cholesterol efflux compared with normobilirubinemic plasma. Unconjugated bilirubin (3-17.1 μmol/L) exogenously added to plasma- or apolipoprotein A1-supplemented media also decreased macrophage cholesterol efflux in a concentration- and time-dependent manner. We also showed reduced protein expression of the ATP-binding cassette transporter A1 (ABCA1), a transmembrane cholesterol transporter involved in apolipoprotein A1-mediated cholesterol efflux, in THP-1 macrophages treated with unconjugated bilirubin and in peripheral blood mononuclear cells obtained from hyperbilirubinemic individuals. Furthermore, we demonstrated that bilirubin accelerates the degradation rate of the ABCA1 protein in THP-1 macrophages. Cholesterol efflux from THP-1 macrophages is decreased in the presence of plasma obtained from humans and rats with mild hyperbilirubinemia. A direct effect of unconjugated bilirubin on cholesterol efflux was demonstrated and is associated with decreased ABCA1 protein expression. These data improve our knowledge concerning bilirubin's impact on cholesterol transport and represent an important advancement in our understanding of bilirubin's role in cardiovascular disease. © 2017 The Authors. Published on

Plasma bilirubin values on admission and ventricular remodeling after a first anterior ST-segment elevation acute myocardial infarction.

Science.gov (United States)

Miranda, Berta; Barrabés, José A; Figueras, Jaume; Pineda, Victor; Rodríguez-Palomares, José; Lidón, Rosa-Maria; Sambola, Antonia; Bañeras, Jordi; Otaegui, Imanol; García-Dorado, David

2016-01-01

Bilirubin may elicit cardiovascular protection and heme oxygenase-1 overexpression attenuated post-infarction ventricular remodeling in experimental animals, but the association between bilirubin levels and post-infarction remodeling is unknown. In 145 patients with a first anterior ST-segment elevation acute myocardial infarction (STEMI), we assessed whether plasma bilirubin on admission predicted adverse remodeling (left ventricular end-diastolic volume [LVEDV] increase ≥20% between discharge and 6 months, estimated by magnetic resonance imaging). Patients' baseline characteristics and management were comparable among bilirubin tertiles. LVEDV increased at 6 months (P bilirubin tertiles (10.8 [30.2], 10.1 [22.9], and 12.7 [24.3]%, P = 0.500). Median (25-75 percentile) bilirubin values in patients with and without adverse remodeling were 0.75 (0.60-0.93) and 0.73 (0.60-0.92) mg/dL (P = 0.693). Absence of final TIMI flow grade 3 (odds ratio 3.92, 95% CI 1.12-13.66) and a history of hypertension (2.04, 0.93-4.50), but not admission bilirubin, were independently associated with adverse remodeling. Bilirubin also did not predict the increase in ejection fraction at 6 months. Admission bilirubin values are not related to LVEDV or ejection fraction progression after a first anterior STEMI and do not predict adverse ventricular remodeling. Key messages Bilirubin levels are inversely related to cardiovascular disease, and overexpression of heme oxygenase-1 (the enzyme that determines bilirubin production) has prevented post-infarction ventricular remodeling in experimental animals, but the association between bilirubin levels and the progression of ventricular volumes and function in patients with acute myocardial infarction remained unexplored. In this cohort of patients with a first acute anterior ST-segment elevation myocardial infarction receiving contemporary management, bilirubin levels on admission were not predictive of the changes in left

Comparison of bilirubin level in term infants born by vaginal delivery and C/S

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Ahmad Shah Farhat

2016-12-01

Full Text Available Background: Given the overriding importance of neonatal jaundice and scarcity of studies on the role of route of delivery on its occurrence, this study aimed to investigate the association between neonatal bilirubin level and the route of delivery (i.e., normal vaginal delivery [NVD] and cesarean section [CS]. Methods: This prospective, cross-sectional study was conducted in 2012 in Imam Reza Hospital of Mashhad, Iran, 2012. In all term infants, who met the inclusion criteria, serum bilirubin level was measured by the bili-test device between the second and seventh days after birth. In cases with skin bilirubin level>5 mg/dl, serum bilirubin was also checked. The collected data were analyzed using SPSS, version 16. Results: A total of 182 neonates were enrolled in the study, 56% of whom were male. The mean bilirubin levels in the NVD and CS groups were 9.4±2.9 mg/dl and 9.8±3.4 mg/dl, respectively (P=0.53. Additionally, comparison of the mean bilirubin levels between the two groups based of demographic characteristics demonstrated no significant differences. Conclusion: This study showed no significant correlation between neonatal jaundice in term infants and the route of delivery.

Molecular imprinting polymer with polyoxometalate/carbon nitride nanotubes for electrochemical recognition of bilirubin

International Nuclear Information System (INIS)

Yola, Mehmet Lütfi; Göde, Ceren; Atar, Necip

2017-01-01

Highlights: •Bilirubin-imprinted sensor is developed for the sensitive detection of bilirubin •The prepared based on nanocomposite were characterized by several methods. •Bilirubin-imprinted sensor offers the important advantages •Bilirubin-imprinted sensor is preferred to the other methods for analysis -- Abstract: In this work, a new molecular imprinted sensor based on polyoxometalate (H 3 PW 12 O 40 , POM) functionalized carbon nitride nanotubes (C 3 N 4 NTs) nanocomposite was prepared for bilirubin (BR) analysis. The structures of prepared surfaces based on the nanocomposite were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), x-ray photoelectron spectroscopy (XPS) and energy dispersive x-ray analysis (EDX). After that, BR imprinted electrode on H 3 PW 12 O 40 /C 3 N 4 NTs nanocomposite was developed by cyclic voltammetry (CV) in 100 mM pyrrole containing 25 mM BR. The linearity range and the detection limit of the developed method were calculated as 1.0 × 10 −12 –1.0 × 10 −10 M and 3.0 × 10 −13 M, respectively. In addition, the imprinted sensor was applied to human plasma samples with high recovery and selectivity.

Chronically elevated bilirubin protects from cardiac reperfusion injury in the male Gunn rat.

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Bakrania, B; Du Toit, E F; Ashton, K J; Wagner, K-H; Headrick, J P; Bulmer, A C

2017-08-01

Bilirubin is associated with reduced risk of cardiovascular disease, as evidenced in conditions of mild hyperbilirubinaemia (Gilbert's Syndrome). Little is known regarding myocardial stress resistance in hyperbilirubinaemic conditions or whether life-long exposure modifies cardiac function, which might contribute to protection from cardiovascular disease. Hyperbilirubinaemic rats and littermate controls underwent echocardiography at 3, 6 and 12 months of age, with hearts subsequently assessed for resistance to 30 min of ischaemia. Heart tissue was then collected for assessment of bilirubin content. No difference in baseline cardiac function was evident until 6 months onwards, where Gunn rats demonstrated aortic dilatation and reduced peak ejection velocities. Additionally, duration of ventricular ejection increased progressively, indicating a negative inotropic effect of bilirubin in vivo. Ex vivo analysis of baseline function revealed reduced left ventricular pressure development (LVDP) and contractility in hyperbilirubinaemic rats. Furthermore, stress resistance was improved in Gunn hearts: post-ischaemic recoveries of LVDP (76 ± 22% vs. 29 ± 17% Control, P bilirubin exerts sex-independent effects on vascular structure, myocardial function and ischaemic tolerance, the latter likely mediated via bilirubin's antioxidant properties. © 2017 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

Transcutaneous Bilirubin Nomogram for Healthy Term and Late Preterm Neonates in First 96 Hours of Life.

Science.gov (United States)

Thakkar, Pareshkumar; Chavda, Hardas; Doshi, Vikas

2017-05-15

To develop nomogram of Transcutaneous Bilirubin among healthy term and late-preterm neonates during first 96 hours of age. Longitudinal observational study. Neonatal unit of a tertiary care Hospital of Central Gujarat, India. 1075 healthy term and late preterm neonates (≥35weeks). Six-hourly transcutaneous bilirubin was obtained from birth to 96 hour of life using Drager JM 103 Transcutaneous Bilirubinometer. Main outcome measures: Nomogram of Transcutaneous Bilirubin with percentile values was obtained, rate of rise of bilirubin was calculated and predictive ability of normative data was analyzed for subsequent need of phototherapy. The age-specific percentile curves and nomogram were developed from the transcutaneous bilirubin readings of 1,010 neonates. Rate of rise in first 12 hour was 0.2 mg/dL and was 0.17 mg/dL in 12 to 24 hour of life which decreased on second day of life. Neonates who required phototherapy had consistently higher readings of transcutaneous bilirubin and also higher rate of rise in first 48 hrs. Neonates whose transcutaneous bilirubin is above the 50th percentile should be monitored for the development of significant hyperbilirubinemia.

Conformational analysis and circular dichroism of bilirubin, the yellow pigment of jaundice

Science.gov (United States)

Lightner, David A.; Person, Richard; Peterson, Blake; Puzicha, Gisbert; Pu, Yu-Ming; Bojadziev, Stefan

1991-06-01

Conformational analysis of (4Z, 15Z)-bilirubin-IX(alpha) by molecular mechanics computations reveals a global energy minimum folded conformation. Powerful added stabilization is achieved through intramolecular hydrogen bonding. Theoretical treatment of bilirubin as a molecular exciton predicts an intense bisignate circular dichroism spectrum for the folded conformation: (Delta) (epsilon) is congruent to 270 L (DOT) mole-1 (DOT) cm-1 for the $OM450 nm electronic transition(s). Synthesis of bilirubin analogs with propionic acid groups methylated at the (alpha) or (beta) position introduces an allosteric effect that allows for an optical resolution of the pigments, with enantiomers exhibiting the theoretically predicted circular dichroism.

Patched Skin Bilirubin Assay to Monitor Neonates Born Extremely Preterm Undergoing Phototherapy.

Science.gov (United States)

De Luca, Daniele; Dell'Orto, Valentina

2017-09-01

To verify the reliability and safety of transcutaneous bilirubin (TcB) measurements in patched skin areas in neonates born extremely preterm under phototherapy. Sixty neonates (bilirubin (TSB), lactate, pH, hemoglobin, and skin temperature were measured within 10 minutes of the TcB assay. Clinicians were blinded to TcB values, and clinical decisions about phototherapy were made with the TSB measurement only. TcB and TSB significantly were correlated (r = 0.84; P bilirubin passage. TcB overestimated TSB, and this may expose infants born preterm to unnecessary phototherapy, although it could spare approximately 65% of TSB assays. Copyright © 2017 Elsevier Inc. All rights reserved.

Predictors of the change in bilirubin levels over twelve weeks of treatment with atazanavir

LENUS (Irish Health Repository)

Cotter, Aoife G

2013-05-16

AbstractObjectiveTo determine the factors associated with change in bilirubin concentration 12 weeks after the initiation of an atazanavir (ATV)-containing antiretroviral regimen.MethodsWe performed a retrospective case note review of all patients prescribed ATV between January 2004 and October 2007 in a cohort of HIV infected subjects. Data collected included baseline demographics, hepatitis B and C serology, current antiretroviral therapy, baseline and week 12 routine bloods. The primary endpoint was the change in bilirubin concentration at 12 weeks after start of ATV. Multvariable linear regression was performed to assess the relationships between the change in bilirubin and variables of interest. Results: Eighty-three ATV-treated patients were included in the analysis of whom 46 (60.5%) were hepatitis C antibody positive. The median (interquartile range) change in bilirubin by week 12 was 16 (4, 22) umol\\/L; only 1 patient developed grade 4 hyperbilirubinaemia at week 12. After controlling for baseline bilirubin levels, HCV seropositivity and baseline ALP were associated with a smaller change in bilirubin over the 12 weeks with a trend towards lower increases in those receiving tenofovir. Sensitivity analyses reported similar associations with methadone use and injection drug use, when these variables replaced HCV sero-positivity in the model. Conclusion: Patients with hepatitis C co-infection experience smaller changes in bilirubin upon exposure to ATV. Although the underlying mechanism for this association remains unclear, these data support the safe use of this drug in this patient setting. Further research into the clinical predictors of ATV-related hyperbilirubinaemia is warranted.

Evaluation of BiliCare™ transcutaneous bilirubin device in Japanese newborns.

Science.gov (United States)

Yamana, Keiji; Morioka, Ichiro; Kurokawa, Daisuke; Fukushima, Sachiyo; Nishida, Kosuke; Ohyama, Shohei; Nishimura, Noriyuki; Nozu, Kandai; Taniguchi-Ikeda, Mariko; Nagase, Hiroaki; Fujioka, Kazumichi; Iwatani, Sota; Nakamura, Hajime; Iijima, Kazumoto

2017-10-01

Non-invasive transcutaneous bilirubin (TcB) monitoring has been widely used to screen for hyperbilirubinemia. TcB measured using the recently developed BiliCare™ system, however, has not been fully evaluated. One hundred and seven TcB measurements were obtained from 82 Japanese newborns ≥35 weeks' gestational age within 2 weeks after birth. Measurements were taken at the scaphoid fossa, conchal cavity, and lobe of the ear using BiliCare. BiliCare TcB were compared with total serum bilirubin (TB) and TcB obtained using another bilirubinometer (JM-105™). Transcutaneous bilirubin measured at all three sites significantly correlated with TB (r = 0.91, 0.93, and 0.93 at the scaphoid fossa, conchal cavity, and lobe, respectively). The mean differences were 0.1, -0.3, and 3.6 at the scaphoid fossa, conchal cavity, and lobe, respectively. BiliCare TcB at the scaphoid fossa significantly correlated with that using the JM-105 (r = 0.91). The mean difference was 0.0. BiliCare, however, produced a significantly higher and lower TcB than the JM-105 for TB bilirubin measurements taken at the scaphoid fossa or conchal cavity using BiliCare were more reliable than those at the earlobe. BiliCare TcB differed from those of the JM-105, for TB <7 or ≥15 mg/dL. © 2017 Japan Pediatric Society.

Higher Bilirubin Levels of Healthy Living Liver Donors Are Associated With Lower Posttransplant Hepatocellular Carcinoma Recurrence.

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Han, Sangbin; Yang, Ju Dong; Sinn, Dong Hyun; Ko, Justin Sangwook; Kim, Jong Man; Shin, Jun Chul; Son, Hee Jeong; Gwak, Mi Sook; Joh, Jae-Won; Kim, Gaab Soo

2016-09-01

Serum bilirubin level, which may reflect the host defense against increased oxidative stress, is inversely associated with the risk of cancer development. In liver transplantation, the intrinsic bilirubin metabolism of donor liver is subsequently translated into recipient. Thus, we hypothesized that liver transplantation conducted with living donors with higher serum bilirubin reduces hepatocellular carcinoma (HCC) recurrence. Two hundred fifty recipients who underwent liver transplantation for treating HCC within the Milan criteria were included in the study. The association between donor preoperative total bilirubin concentration and the risk of HCC recurrence was analyzed using the Fine and Gray regression model with posttransplant death as a competing risk event with adjustment for tumor biology including α-fetoprotein, histological differentiation, and microvascular invasion. All donors were confirmed to have no underlying hepatobiliary diseases or hematological disorders. Donor preoperative total bilirubin concentration was 0.7 mg/dL in median and ranged from 0.2 to 2.7 mg/dL. Thirty-five (14.0%) recipients developed HCC recurrence. Multivariable analysis demonstrated that donor preoperative total bilirubin concentration was inversely associated with the recurrence risk (hazard ratio, 0.22; 95% confidence interval, 0.07-0.72; P = 0.013). The highest (≥1.0 mg/dL) versus lowest (≤0.6 mg/dL) tertile of donor preoperative total bilirubin showed a significant reduction of the recurrence risk (hazard ratio, 0.28; 95% confidence interval, 0.11-0.70; P = 0.006). Hepatocellular carcinoma recurrence risk decreases in relation to the increase in total serum bilirubin level of healthy living donors without underlying hepatobiliary or hematological disorders. Further validation of bilirubin as a potent anticancer substance against HCC is warranted.

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

Science.gov (United States)

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

Physiologic Doses of Bilirubin Contribute to Tolerance of Islet Transplants by Suppressing the Innate Immune Response.

Science.gov (United States)

Adin, Christopher A; VanGundy, Zachary C; Papenfuss, Tracey L; Xu, Feng; Ghanem, Mostafa; Lakey, Jonathan; Hadley, Gregg A

2017-01-24

Bilirubin has been recognized as a powerful cytoprotectant when used at physiologic doses and was recently shown to have immunomodulatory effects in islet allograft transplantation, conveying donor-specific tolerance in a murine model. We hypothesized that bilirubin, an antioxidant, acts to suppress the innate immune response to islet allografts through two mechanisms: 1) by suppressing graft release of damage-associated molecular patterns (DAMPs) and inflammatory cytokines, and 2) by producing a tolerogenic phenotype in antigen-presenting cells. Bilirubin was administered intraperitoneally before pancreatic procurement or was added to culture media after islet isolation in AJ mice. Islets were exposed to transplant-associated nutrient deprivation and hypoxia. Bilirubin significantly decreased islet cell death after isolation and hypoxic stress. Bilirubin supplementation of islet media also decreased the release of DAMPs (HMGB1), inflammatory cytokines (IL-1β and IL-6), and chemokines (MCP-1). Cytoprotection was mediated by the antioxidant effects of bilirubin. Treatment of macrophages with bilirubin induced a regulatory phenotype, with increased expression of PD-L1. Coculture of these macrophages with splenocytes led to expansion of Foxp3+ Tregs. In conclusion, exogenous bilirubin supplementation showed cytoprotective and antioxidant effects in a relevant model of islet isolation and hypoxic stress. Suppression of DAMP release, alterations in cytokine profiles, and tolerogenic effects on macrophages suggest that the use of this natural antioxidant may provide a method of preconditioning to improve outcomes after allograft transplantation.

Circulating Total Bilirubin and Risk of Incident Cardiovascular Disease in the General Population

NARCIS (Netherlands)

Kunutsor, Setor K.; Bakker, Stephan J. L.; Gansevoort, Ronald T.; Chowdhury, Rajiv; Dullaart, Robin P. F.

OBJECTIVE: To assess the association of circulating total bilirubin and cardiovascular disease (CVD) risk in a new prospective study and to determine whether adding information on total bilirubin values to established cardiovascular risk factors is associated with improvement in prediction of CVD

Bilirubin in Urine: MedlinePlus Lab Test Information

Science.gov (United States)

... K. Brunner & Suddarth's Handbook of Laboratory and Diagnostic Tests. 2 nd Ed, Kindle. Philadelphia: Wolters Kluwer Health, Lippincott Williams & Wilkins; c2014. Bilirubin (Urine); 86–87 p. Lab ...

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

Science.gov (United States)

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.

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

Science.gov (United States)

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; Pbilirubin 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

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

Science.gov (United States)

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

2016-08-03

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.

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

Science.gov (United States)

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

2016-01-05

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. Copyright © 2015. Published by Elsevier Ireland Ltd.

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

Science.gov (United States)

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. Copyright © 2012 Elsevier B.V. All rights reserved.

The effect of elimination of environmental light on the metabolism of unconjugated bilirubin in the Gunn rat

International Nuclear Information System (INIS)

Zenone, E.A.; Stoll, M.S.; Ostrow, J.D.

1982-01-01

In the homozygous jaundiced Gunn rat, bilirubin catabolism is augmented by intense illumination (phototherapy) and by induction of microsomal cytochrome P448. To assess the relative importance of less intense environmental light versus intrinsic mechanisms in the maintenance of bilirubin turnover, Gunn rats were kept for three weeks under either ordinary laboratory lighting (0.3-0.8 mW/cm2, wavelength range 400-600 nm) or in absolute darkness. No differences in plasma concentration, miscible pool, turnover of bilirubin, or in hepatic cytochrome P448 activity were noted between the two groups over this period. A greater than twofold increase in the biliary excretion of unconjugated bilirubin was noted in the animals maintained under light, but this represented only 2% of total bilirubin turnover. These results suggest that intrinsic(enzymatic .) pathways are of primary importance in the maintenance of bilirubin metabolism in the glucuronyltransferase-deficient state under ordinary levels of environmental light

Computational chemical analysis of unconjugated bilirubin anions and insights into pKa values clarification

Science.gov (United States)

Vega-Hissi, Esteban G.; Estrada, Mario R.; Lavecchia, Martín J.; Pis Diez, Reinaldo

2013-01-01

The pKa, the negative logarithm of the acid dissociation equilibrium constant, of the carboxylic acid groups of unconjugated bilirubin in water is a discussed issue because there are quite different experimental values reported. Using quantum mechanical calculations we have studied the conformational behavior of unconjugated bilirubin species (in gas phase and in solution modeled implicitly and explicitly) to provide evidence that may clarify pKa values because of its pathophysiological relevance. Our results show that rotation of carboxylate group, which is not restricted, settles it in a suitable place to establish stronger interactions that stabilizes the monoanion and the dianion to be properly solvated, demonstrating that the rationalization used to justify the high pKa values of unconjugated bilirubin is inappropriate. Furthermore, low unconjugated bilirubin (UCB) pKa values were estimated from a linear regression analysis.

Bilirubin nomogram for prediction of significant hyperbilirubinemia in north Indian neonates.

Science.gov (United States)

Pathak, Umesh; Chawla, Deepak; Kaur, Saranjit; Jain, Suksham

2013-04-01

(i) To construct hour-specific serum total bilirubin (STB) nomogram in neonates born at =35 weeks of gestation; (ii)To evaluate efficacy of pre-discharge bilirubin measurement in predicting hyperbilirubinemia needing treatment. Diagnostic test performance in a prospective cohort study. Teaching hospital in Northern India. Healthy neonates with gestation =35 weeks or birth weight =2000 g. Serum total bilirubin was measured in all enrolled neonates at 24 ± 6, 72-96 and 96-144 h of postnatal age and when indicated clinically. Neonates were followed up during hospital stay and after discharge till completion of 7th postnatal day. Key outcome was significant hyperbilirubinemia (SHB) defined as need of phototherapy based on modified American Academy of Pediatrics (AAP) guidelines. In neonates born at 38 or more weeks of gestation middle line and in neonates born at 37 or less completed weeks of gestation, lower line of phototherapy thresholds were used to initiate phototherapy. For construction of nomogram, STB values were clubbed in six-hour epochs (age ± 3 hours) for postnatal age up to 48 h and twelve-hour epochs (age ± 6 hours) for age beyond 48 h. Predictive ability of the nomogram was assessed by calculating sensitivity, specificity, positive predictive value, negative predictive value and likelihood ratio, by plotting receiver-operating characteristics (ROC) curve and calculating c-statistic. 997 neonates (birth weight: 2627 ± 536 g, gestation: 37.8 ± 1.5 weeks) were enrolled, of which 931 completed followup. Among enrolled neonates 344 (34.5%) were low birth weight. Rate of exclusive breastfeeding during hospital stay was more than 80%. Bilirubin nomogram was constructed using 40th, 75th and 95th percentile values of hour-specific bilirubin. Pre-discharge STB of =95th percentile was assigned to be in high-risk zone, between 75th and 94th centile in upper-intermediate risk zone, between 40th and 74th centile in lower-intermediate risk zone and below 40th

Continuous de novo biosynthesis of haem and its rapid turnover to bilirubin are necessary for cytoprotection against cell damage

Science.gov (United States)

Takeda, Taka-aki; Mu, Anfeng; Tai, Tran Tien; Kitajima, Sakihito; Taketani, Shigeru

2015-01-01

It is well known that haem serves as the prosthetic group of various haemoproteins that function in oxygen transport, respiratory chain, and drug metabolism. However, much less is known about the functions of the catabolites of haem in mammalian cells. Haem is enzymatically degraded to iron, carbon monoxide (CO), and biliverdin, which is then converted to bilirubin. Owing to difficulties in measuring bilirubin, however, the generation and transport of this end product remain unclear despite its clinical importance. Here, we used UnaG, the recently identified bilirubin-binding fluorescent protein, to analyse bilirubin production in a variety of human cell lines. We detected a significant amount of bilirubin with many non-blood cell types, which was sensitive to inhibitors of haem metabolism. These results suggest that there is a basal level of haem synthesis and its conversion into bilirubin. Remarkably, substantial changes were observed in the bilirubin generation when cells were exposed to stress insults. Since the stress-induced cell damage was exacerbated by the pharmacological blockade of haem metabolism but was ameliorated by the addition of biliverdin and bilirubin, it is likely that the de novo synthesis of haem and subsequent conversion to bilirubin play indispensable cytoprotective roles against cell damage. PMID:25990790

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

Science.gov (United States)

Orlov, Sergey; Goncharova, Iryna; Urbanová, Marie

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.

Serum total bilirubin levels are negatively correlated with metabolic syndrome in aged Chinese women: a community-based study.

Science.gov (United States)

Zhong, P; Sun, D M; Wu, D H; Li, T M; Liu, X Y; Liu, H Y

2017-01-26

We evaluated serum total bilirubin levels as a predictor for metabolic syndrome (MetS) and investigated the relationship between serum total bilirubin levels and MetS prevalence. This cross-sectional study included 1728 participants over 65 years of age from Eastern China. Anthropometric data, lifestyle information, and previous medical history were collected. We then measured serum levels of fasting blood-glucose, total cholesterol, triglycerides, and total bilirubin, as well as alanine aminotransferase activity. The prevalence of MetS and each of its individual component were calculated per quartile of total bilirubin level. Logistic regression was used to assess the correlation between serum total bilirubin levels and MetS. Total bilirubin level in the women who did not have MetS was significantly higher than in those who had MetS (Pbilirubin quartiles were linearly and negatively correlated with MetS prevalence and hypertriglyceridemia (HTG) in females (Pbilirubin was an independent predictor of MetS for females (OR: 0.910, 95%CI: 0.863-0.960; P=0.001). The present study suggests that physiological levels of serum total bilirubin might be an independent risk factor for aged Chinese women, and the prevalence of MetS and HTG are negatively correlated to serum total bilirubin levels.

Measurements of neonatal bilirubin and albumin concentrations : a need for improvement and quality control

NARCIS (Netherlands)

van Imhoff, Deirdre E.; Dijk, Peter H.; Weykamp, Cas W.; Cobbaert, Christa M.; Hulzebos, Christian V.

Accurate and precise bilirubin and albumin measurements are essential for proper management of jaundiced neonates. Data hereon are lacking for Dutch laboratories. We aimed to determine variability of measurements of bilirubin and albumin concentrations typical for (preterm) neonates. Aqueous, human

Measurements of neonatal bilirubin and albumin concentrations: a need for improvement and quality control

NARCIS (Netherlands)

Imhoff, D.E. van; Dijk, P.H.; Weykamp, C.W.; Cobbaert, C.M.; Hulzebos, C.V.; Liem, K.D.; et al.,

2011-01-01

Accurate and precise bilirubin and albumin measurements are essential for proper management of jaundiced neonates. Data hereon are lacking for Dutch laboratories. We aimed to determine variability of measurements of bilirubin and albumin concentrations typical for (preterm) neonates. Aqueous, human

PEGylated bilirubin nanoparticle as an anti-oxidative and anti-inflammatory demulcent in pancreatic islet xenotransplantation.

Science.gov (United States)

Kim, Min Jun; Lee, Yonghyun; Jon, Sangyong; Lee, Dong Yun

2017-07-01

Transplanted islets suffer hypoxic stress, which leads to nonspecific inflammation. This is the major cause of islet graft failure during the early stage of intrahepatic islet transplantation. Although bilirubin has shown potent anti-oxidative and anti-inflammatory functions, its clinical applications have been limited due to its insolubility and short half-life. To overcome this problem, novel amphiphilic bilirubin nanoparticles are designed. Hydrophilic poly(ethylene glycol) (PEG) is conjugated to the hydrophobic bilirubin molecule. Then, the PEG-bilirubin conjugates form nanoparticles via self-assembly, i.e., so-called to BRNPs. BRNPs can protect islet cells not only from chemically induced oxidative stress by scavenging reactive oxygen species molecules, but also from activated macrophages by suppressing cytokine release. Importantly, in vivo experiments demonstrate that BRNP treatment can dramatically and significantly prolong islet graft survival compared to bilirubin treatment. In addition, immunohistochemical analysis shows BRNPs have potent anti-oxidative and anti-inflammatory capabilities. Collectively, novel BRNPs can be a new potent remedy for successful islet transplantation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Blue emitting copper nanoclusters as colorimetric and fluorescent probe for the selective detection of bilirubin

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R. S., Aparna; J. S., Anjali Devi; John, Nebu; Abha, K.; S. S., Syamchand; George, Sony

2018-06-01

Hurdles to develop point of care diagnostic methods restrict the translation of progress in the health care sector from bench side to bedside. In this article a simple, cost effective fluorescent as well as colorimetric nanosensor was developed for the early and easy detection of hyperbilirubinemia. A stable, water soluble bovine serum albumin stabilised copper nanocluster (BSA CuNC) was used as the fluorescent probe which exhibited strong blue emission (404 nm) upon 330 nm excitation. The fluorescence of the BSA CuNC can be effectively quenched by the addition of bilirubin by the formation of copper-bilirubin complex. Meanwhile the copper-bilirubin complex resulted in an observable colour change from pale violet to green facilitating colorimetric detection. The prepared sensor displayed good selectivity and sensitivity over other co-existing molecules, and can be used for quantifying bilirubin with a detection limit down to 257 fM. Additionally, the as-prepared probe was coated on a paper strip to develop a portable paper strip sensor of bilirubin. Moreover, the method was successfully applied in real sample analysis and obtained promising result.

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

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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. Copyright © 2015

Unbound Bilirubin and Auditory Neuropathy Spectrum Disorder in Late Preterm and Term Infants with Severe Jaundice.

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Amin, Sanjiv B; Wang, Hongyue; Laroia, Nirupama; Orlando, Mark

2016-06-01

This study evaluates whether unbound bilirubin is a better predictor of auditory neuropathy spectrum disorder (ANSD) than total serum bilirubin (TSB) or the bilirubin:albumin molar ratio (BAMR) in late preterm and term neonates with severe jaundice (TSB ≥20 mg/dL or TSB that met exchange transfusion criteria). Infants ≥34 weeks' gestation with severe jaundice during the first 2 weeks of life were eligible for the prospective observational study. A comprehensive auditory evaluation was performed within 72 hours of peak TSB. ANSD was defined as absent or abnormal auditory brainstem evoked response waveform morphology at 80-decibel click intensity in the presence of normal outer hair cell function. TSB, serum albumin, and unbound bilirubin were measured using the colorimetric, bromocresol green, and modified peroxidase method, respectively. Five of 44 infants developed ANSD. By logistic regression, peak unbound bilirubin but not peak TSB or peak BAMR was associated with ANSD (OR, 4.6; 95% CI, 1.6-13.5; P = .002). On comparing receiver operating characteristic curves, the area under the curve for unbound bilirubin (0.92) was significantly greater (P = .04) compared with the area under the curve for TSB (0.50) or BAMR (0.62). Unbound bilirubin is a more sensitive and specific predictor of ANSD than TSB or BAMR in late preterm and term infants with severe jaundice. Copyright © 2016 Elsevier Inc. All rights reserved.

Studying neonatal bilirubin encephalopathy with conventional MRI, MRS, and DWI

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Wang, Xiaoyi; Wu, Wulin; Chineah, Ashley; Liu, Fan; Liao, Weihua; Hou, Bob L.; Zhang, Ping

2008-01-01

The purpose of this study was to evaluate the diagnostic value of conventional magnetic resonance imaging (MRI), proton magnetic resonance spectroscopy ( 1 H-MRS), and diffusion-weighted imaging (DWI) for neonatal bilirubin encephalopathy. We collected conventional MRI in 24 neonates with neonatal bilirubin encephalopathy. We performed 1 H-MRS and DWI sequences to nine of the 24 patients and seven age-matched healthy control subjects. Multiple-voxel 1 H-MRS data were acquired using PRESS pulse sequence with TE=135 ms and TR=1500 ms. The spectroscopic regions of interest were the bilateral basal ganglia and thalamus with a 1.0 mL spatial resolution. The data from DWI were collected by using a single shot-spin echo-echo planar imaging sequence with TR/TE: 2900/98, and imaging regions were also focused on the bilateral basal ganglia and thalamus. Nineteen of the 24 patients had abnormal T 1 -weighted image hyperintensity in the globus pallidus, but these lesions appeared as normal T 2 -weighted image intensity in the same region. Ten of the 24 patients had T 1 -weighted image high signal intensity in the subthalamic nucleus and appeared as normal intensity in the region for the T 2 -weighted images. The peak area ratios of NAA/Cho and NAA/Cr were significantly decreased (t-test, P 1 H-MRS are important complementary tools in the diagnosis of neonatal bilirubin encephalopathy. The study provides important information for applying these MR modalities to evaluate neonates with bilirubin encephalopathy. (orig.)

Photodamage of the cells in culture sensitized with bilirubin

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Kozlenkova, O. A.; Plavskaya, L. G.; Mikulich, A. V.; Leusenko, I. A.; Tretyakova, A. I.; Plavskii, V. Yu

2016-08-01

It has been shown that exposure to radiation of LED sources of light with an emission band maximum at about 465 and 520 nm having substantially identical damaging effects on animal cells in culture, that are in a logarithmic growth phase and preincubated with pigment. Photobiological effect is caused by photodynamic processes involving singlet oxygen generated by triplet excited sensitizer. Mono-exponential type dependence of cell survival on the energy dose indicates that it is bilirubin that acts as a sensitizer but not its photoproducts. The inclusion of bilirubin in the cells, where it is primarily localized in the mitochondria cells, it is accompanied by multiple amplification photochemical stability compared to pigment molecules bound with albumin

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

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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. Copyright © 2015 the American Physiological Society.

The role of magnetic resonance imaging in the prediction of the neurodevelopmental outcome of acute bilirubin encephalopathy in newborns

OpenAIRE

TATLI, Mustafa Mansur

2009-01-01

Aim: Magnetic resonance imaging (MRI) is widely used in the diagnosis of acute bilirubin encephalopathy, but the relationship between MRI findings and neurodevelopmental outcome in newborns with acute bilirubin encephalopathy remains unclear. The aim of this study was to investigate the relationship between acute bilirubin encephalopathy, MRI findings, and neurodevelopmental outcome. Materials and Methods: The study included 13 infants with acute bilirubin encephalopathy. MRI was performed ...

Is there any relationship between serum levels of total bilirubin and the severity of erectile dysfunction?

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Keskin, Ercüment; Karabakan, Mehmet; Bozkurt, Aliseydi; Hirik, Erkan; Karabulut, İbrahim; Gunay, Murat; Çakan, Murat

2018-04-01

Recent studies have shown that atherosclerosis is associated with erectile dysfunction and the serum bilirubin level. In this study, the serum total bilirubin levels of patients with erectile dysfunction were measured to investigate the relationship between the levels of erectile dysfunction and total bilirubin. A total of 94 patients with erectile dysfunction were divided into three groups; severe erectile dysfunction (33 patients), moderate erectile dysfunction (31 patients), and mild erectile dysfunction (30 patients). In addition, a control group was formed with 31 healthy men. The International Index of Erectile Function-5 Questionnaire was used to measure the quality of erection in all the groups. The body mass index was calculated for all the participants. The serum glucose, low-density lipoprotein and high-density lipoprotein, cholesterol, triglyceride, total bilirubin, and total testosterone levels were also determined. No statistically significant difference was observed between the groups in terms of the mean age, hypertension, smoking status, alcohol use, cardiovascular diseases, hepatobiliary disease, diabetes mellitus, and levels of total testosterone, low-density lipoprotein-cholesterol, and triglyceride. However, high-density lipoprotein, body mass index, and total bilirubin were significantly lower compared to the control group (p < 0.001). The serum total bilirubin level was found to be 0.41 ± 0.21 ng/dL in the severe erectile dysfunction, 0.43 ± 0.19 ng/dL in the moderate erectile dysfunction, and 0.48 ± 0.11 ng/dL in the mild erectile dysfunction groups (p < 0.001). Considering the significant differences between the erectile dysfunction and control groups in terms of serum total bilirubin levels, a low level of bilirubin may have a role in the etiology of erectile dysfunction.

Relationship between serum bilirubin concentrations and diabetic nephropathy in Shanghai Han's patients with type 1 diabetes mellitus.

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Li, Xu; Zhang, Lei; Chen, Haibing; Guo, Kaifeng; Yu, Haoyong; Zhou, Jian; Li, Ming; Li, Qing; Li, Lianxi; Yin, Jun; Liu, Fang; Bao, Yuqian; Han, Junfeng; Jia, Weiping

2017-03-31

Recent studies highlight a negative association between total bilirubin concentrations and albuminuria in patients with type 2 diabetes mellitus. Our study evaluated the relationship between bilirubin concentrations and the prevalence of diabetic nephropathy (DN) in Chinese patients with type 1 diabetes mellitus (T1DM). A total of 258 patients with T1DM were recruited and bilirubin concentrations were compared between patients with or without diabetic nephropathy. Multiple stepwise regression analysis was used to examine the relationship between bilirubin concentrations and 24 h urinary microalbumin. Binary logistic regression analysis was performed to assess independent risk factors for diabetic nephropathy. Participants were divided into four groups according to the quartile of total bilirubin concentrations (Q1, 0.20-0.60; Q2, 0.60-0.80; Q3, 0.80-1.00; Q4, 1.00-1.90 mg/dL) and the chi-square test was used to compare the prevalence of DN in patients with T1DM. The median bilirubin level was 0.56 (interquartile: 0.43-0.68 mg/dL) in the DN group, significantly lower than in the non-DN group (0.70 [interquartile: 0.58-0.89 mg/dL], P 1). Spearman's correlational analysis showed bilirubin concentrations were inversely correlated with 24 h urinary microalbumin (r = -0.13, P 1.90% to 2.00%. High bilirubin concentrations are independently and negatively associated with albuminuria and the prevalence of DN in patients with T1DM.

Influence of photoisomers in bilirubin determinations on Kodak Ektachem and Hitachi analysers in neonatal specimens study of the contribution of structural and configurational isomers.

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Gulian, J M; Dalmasso, C; Millet, V; Unal, D; Charrel, M

1995-08-01

We compared data obtained with the Kodak Ektachem and Hitachi 717 Analysers and HPLC from 83 neonates under phototherapy. Total bilirubin values determined with the Kodak and Hitachi are in good agreement, but we observed a large discrepancy in the results for conjugated (Kodak) and direct (Hitachi) bilirubin. HPLC revealed that all the samples contained configurational isomers, while only 7.7% and 30.8% contained conjugated bilirubin and structural isomers, respectively. We developed a device for the specific and quantitative production of configurational or structural isomers, by irradiation with blue or green light. In vitro, total bilirubin values are coherent for the routine analysers in the presence of configurational or structural isomers. With configurational isomers, unconjugated bilirubin (Kodak) is lower than total bilirubin (Kodak), and conjugated bilirubin (Kodak) is always equal to zero, so the apparatus gives a false positive response for delta bilirubin. In contrast, the direct bilirubin (Hitachi) is constant. Furthermore, in the presence of structural isomers, unconjugated bilirubin (Kodak) is unexpectedly higher than total bilirubin (Kodak), conjugated bilirubin (Kodak) is proportional to the quantity of these isomers, and direct bilirubin (Hitachi) is constant. The contribution of photoisomers in bilirubin measurements is discussed.

Cell damage by bilirubin and light

International Nuclear Information System (INIS)

Granli, T.

1993-01-01

Large doses of light are given to newborns during phototherapy for hyperbilirubinemia. Tissues containing concentrations of bilirubin almost in the mM range may be subjected to irradiation. Therefore it is of interest to study cellular effects of light and bilirubin on cells. In order to select the optimal wavelength, possible detrimental effects of light on cells must be taken into consideration among a number of other factors. In this study cellular effects of selected wavelengths of blue-green light are compared. It is not clear whether cullular damage occurs in vivo during phototherapy of newborns. Since a possibility exists that some adverse effects are caused by light, one should choose wavelengths where these effects are minimal without loosing therapeutic efficiency. Todays knowledge of the photochemical mechanisms of phototherapy, indicates that short waved light with wavelengths below 450 nm has a low therapeutic effect. The data in this paper indicate that the cellular damage is most severe at short wavelengths, and these should be reduced to a minimum in the spectra of phototherapy lamps. Further studies of possible side effects of phototherapy should be made. 64 refs., 34 figs., 1 tab

Prevalence of Bilirubin Encephalopathy in Calabar, South-South Nigeria: A Five-year Review Study

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Sunny Oteikwu Ochigbo

2016-03-01

Full Text Available Background: Bilirubin encephalopathy is a clinical syndrome, associated with bilirubin toxicity in the central nervous system, resulting in chronic and permanent sequelae. It has been estimated that approximately 60% and 80% of term and preterm newborns develop jaundice in the first week of life, respectively. In the present study, we aimed to determine the prevalence, morbidity, and mortality of bilirubin encephalopathy in the neonatal unit of the University of Calabar Teaching Hospital, Calabar, Nigeria. Methods: In this retrospective, descriptive review, medical records of all newborns, diagnosed with bilirubin encephalopathy over the past five years (from January 2010 to December 2014, were studied. Information retrieved from the medical records included age, sex, presence of fever, duration of disease, place of delivery, causes of the disease, and selected treatments. Variables such as hospital discharge, discharge against medical advice, and mortality were also evaluated. Results: Out of 2,820 newborns, 21 (0.74% cases were admitted on account of bilirubin encephalopathy. Among these affected cases, 17 (81% were male and 4 (19% were female (male-to-female ratio of 5:1. Based on the findings, 18 newborns (85.7% had pyrexia, while 8 (38.1% and 6 (28.6% cases were hypertonic and hypotonic, respectively upon admission. Only 33.3% of deliveries took place in healthcare facilities. The established factors responsible for jaundice included infection, i.e., septicemia (n=15, 71.4%, ABO incompatibility (n=4, 19.1%, and glucose-6-phosphate-dehydrogenase (G6PD deficiency (n=2, 9.5%. The mean maximum total bilirubin level in subjects was 321.3 μmol/L (range: 242.5–440.3 μmol/L. Also, mortality was reported in 4 (19% out of 21 cases. Conclusion: Based on the findings, neonatal septicemia is associated with bilirubin encephalopathy. Therefore, identification and prompt treatment are of utmost importance in preventing the associated morbidity and

The Relationship between Serum Bilirubin and Elevated Fibrotic Indices among HBV Carriers: A Cross-Sectional Study of a Chinese Population

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Min Du

2016-12-01

Full Text Available The study probed the association between bilirubin and hepatitis B virus (HBV infection and progression. A cross-sectional analysis of 28,500 middle aged and elderly Chinese participants was performed to analyze the differences of bilirubin in terms of hepatitis B surface antigen (HBsAg positive or negative and the correlation between bilirubin and severity of hepatic fibrosis estimated by non-invasive indices. Bilirubin was significantly higher in the HBsAg (+ group than the HBsAg (− group. Higher bilirubin levels were consistently associated with elevated liver fibrosis indices among HBsAg carriers. Compared with quartile 1 of total bilirubin (TBil, the multivariable-adjusted ORs (95% CIs for elevated fibrosis indices of quartile 4 were 2.24 (95% CIs, 1.57–3.21 estimated by fibrosis 4 score (FIB-4 and 2.22 (95% CIs, 1.60–3.08 estimated by aspartate transaminase to platelet ratio index (APRI. In addition, direct bilirubin (DBil had a stronger association with elevated liver fibrosis indices than did indirect bilirubin (IBil. Furthermore, the relationship between DBil and elevated fibrosis indices was more robust among participants who were female, overweight or had central fat distribution. These findings suggested that bilirubin levels, especially DBil, were independently associated with an increased risk of increased fibrosis indices.

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

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Levitt DG

2014-09-01

Full Text Available David G Levitt,1 Michael D Levitt2 1Department of Integrative Biology and Physiology, University of Minnesota, Minneapolis, MN, USA; 2Research Service, Veterans Affairs Medical Center, Minneapolis, MN, USAAbstract: 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.Keywords: liver, conjugation, diazo, albumin, Rotor

Can Excess Bilirubin Levels Cause Learning Difficulties?

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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…

Thyroid hormone uptake in cultured rat anterior pituitary cells: effects of energy status and bilirubin

NARCIS (Netherlands)

F.W.J.S. Wassen (Frank); E.P.C.M. Moerings (Ellis); H. van Toor (Hans); G. Hennemann; M.E. Everts (Maria)

2000-01-01

textabstractTransport of thyroxine (T(4)) into the liver is inhibited in fasting and by bilirubin, a compound often accumulating in the serum of critically ill patients. We tested the effects of chronic and acute energy deprivation, bilirubin and its precursor

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

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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 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.

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

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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.

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

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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

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

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Gianfranco Cervellin

Full Text Available 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.

Simultaneous estimation of transcutaneous bilirubin, hemoglobin, and melanin based on diffuse reflectance spectroscopy

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Nishidate, Izumi; Abdul, Wares MD.; Ohtsu, Mizuki; Nakano, Kazuya; Haneishi, Hideaki

2018-02-01

We propose a method to estimate transcutaneous bilirubin, hemoglobin, and melanin based on the diffuse reflectance spectroscopy. In the proposed method, the Monte Carlo simulation-based multiple regression analysis for an absorbance spectrum in the visible wavelength region (460-590 nm) is used to specify the concentrations of bilirubin (Cbil), oxygenated hemoglobin (Coh), deoxygenated hemoglobin (Cdh), and melanin (Cm). Using the absorbance spectrum calculated from the measured diffuse reflectance spectrum as a response variable and the extinction coefficients of bilirubin, oxygenated hemoglobin, deoxygenated hemoglobin, and melanin, as predictor variables, multiple regression analysis provides regression coefficients. Concentrations of bilirubin, oxygenated hemoglobin, deoxygenated hemoglobin, and melanin, are then determined from the regression coefficients using conversion vectors that are numerically deduced in advance by the Monte Carlo simulations for light transport in skin. Total hemoglobin concentration (Cth) and tissue oxygen saturation (StO2) are simply calculated from the oxygenated hemoglobin and deoxygenated hemoglobin. In vivo animal experiments with bile duct ligation in rats demonstrated that the estimated Cbil is increased after ligation of bile duct and reaches to around 20 mg/dl at 72 h after the onset of the ligation, which corresponds to the reference value of Cbil measured by a commercially available transcutaneous bilirubin meter. We also performed in vivo experiments with rats while varying the fraction of inspired oxygen (FiO2). Coh and Cdh decreased and increased, respectively, as FiO2 decreased. Consequently, StO2 was dramatically decreased. The results in this study indicate potential of the method for simultaneous evaluation of multiple chromophores in skin tissue.

Intracellular distribution of organic anions (131I-BSP and 3H-bilirubin)

International Nuclear Information System (INIS)

Kamisaka, Kazuaki; Iida, Yoshitaka; Azegami, Nobuhisa; Oda, Hiroyuki; Maezawa, Hidenori

1981-01-01

About 2 μ Ci of 131 I-BSP were injected intravenously into normal wister rats and the distributions of the isotope were determined in subcellular fractions of rat liver by the method of De Duve et al. Approximately 33% of the total activity was localized in nuclear fraction and cell debris, 28.5% was in supernatant fraction, 16.5% in microsome, 13% in lysosome and 8% in mitochondrial fraction. The subcellular distributions of radioactivity remained unchanged for 1.5 hours. Using autoradiographic method, the intracellular distribution of 3 H-bilirubin was examined by the extracted liver, 5 min, after intravenous injection of 3 H-bilirubin. 3 H-bilirubin was localized mainly in the cytoplasm and small amounts was already distributed on the canalicular membrane. It is suggested that these small molecules are mainly transported through cytoplasm and there is no specific pathway for the hepatic intracellular transport system. (author)

Bilirubin: an endogenous molecule with antiviral activity in vitro.

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Rosaria eSantangelo

2012-03-01

Full Text Available Bilirubin-IX-alpha (BR is the final product of heme metabolism through the heme oxygenase/biliverdin reductase (HO/BVR system. Previous papers reported on the microbicidal effects of the HO by-products biliverdin-IX-alpha, carbon monoxide and iron, through either direct or indirect mechanisms. In this paper the evidence of a virucidal effect of BR against human herpes simplex virus type 1 (HSV-1 and the enterovirus EV71 was provided. Bilirubin-IX-alpha, at concentrations 1-10 µM, close to those found in blood and tissues, significantly reduced HSV-1 and EV71 replication in Hep-2 and Vero cell lines, respectively. Bilirubin-IX-alpha inhibited viral infection of Hep-2 and Vero cells when given 2 hours before, concomitantly and 2 hours after viral infection. Furthermore, BR retained its antiviral activity even complexed with a saturating concentration of human serum-albumin. Moreover, 10 µM BR increased the formation of nitric oxide and the phosphorylation of JNK in Vero and Hep-2 cell lines, respectively, thus implying a role of these two pathways in the mechanism of antiviral activity of the bile pigment. In conclusion, these results support the antiviral effect of BR against HSV-1 and enterovirus in vitro, and put the basis for further basic and clinical studies to understand the real role of BR as an endogenous antiviral molecule.

Bilirubin nanoparticles ameliorate allergic lung inflammation in a mouse model of asthma.

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Kim, Dong Eon; Lee, Yonghyun; Kim, MinGyo; Lee, Soyoung; Jon, Sangyong; Lee, Seung-Hyo

2017-09-01

Although asthma, a chronic inflammatory airway disease, is relatively well-managed by inhaled corticosteroids, the side effects associated with the long-term use of these agents precipitate the need for alternative therapeutic options based on differing modes of action. Bilirubin, a potent endogenous antioxidant, and anti-inflammatory molecule have been shown to ameliorate asthmatic symptoms; however, its clinical translation has been limited owing to its water insolubility and associated potential toxicity. Here we report the first application of bilirubin-based nanoparticles (BRNPs) as a nanomedicine for the treatment of allergic lung inflammatory disease. BRNPs were prepared directly from self-assembly of PEGylated bilirubin in aqueous solution and had a hydrodynamic diameter of ∼100 nm. Because allergen-specific type 2 T-helper (Th2) cells play a key role in the pathogenesis and progression of allergic asthma, the effects of BRNPs on Th2 immune responses were investigated both in vivo and in vitro. BRNPs after intravenous injection (i.v.) showed much higher serum concentration and a longer circulation time of bilirubin than the intraperitoneal injection (i.p.) of BRNPs or unconjugated bilirubin (UCB). The anti-asthmatic effects of BRNPs were assessed in a mouse model of allergen-induced asthma. Compared with UCB, treatment with BRNPs suppressed the symptoms of experimental allergic asthma and dramatically ameliorated Th2-related allergic lung inflammation. Consistent with these results, BRNPs caused a reduction of Th2 cell populations and the expression of related cytokines by antibody-stimulated CD4 + T cells in vitro. Therefore, our results establish BRNPs as an important immunomodulatory agent that may be useful as a therapeutic for allergic lung inflammatory disease and other immune-mediated disorders. Copyright © 2017 Elsevier Ltd. All rights reserved.

Analysis of Urobilinogen and Urine Bilirubin for Intra-Abdominal Injury in Blunt Trauma Patients

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Gorchynski, Julie

2009-05-01

Full Text Available OBJECTIVE: To determine the point prevalence of urine bilirubin, urine hemoglobin and urobilinogen in blunt trauma patients, and to evaluate its utility as a screening tool for intra-abdominal injury.METHODS: Data analysis of 986 consecutive trauma patients of which 698 were adult blunt trauma patients. Five-hundred sixteen subjects had a urinalysis and a CT scan of the abdomen/pelvis or exploratory laparotomy. We reviewed initial urinalysis results from trauma patients in the emergency department (ED for the presence of urine hemoglobin, uroblinogen and urine bilirubin. Computed tomography (CT scan results and operative reports were reviewed from the trauma registry for evidence of liver laceration, spleen laceration, bowel or mesenteric injuries.RESULTS: There were 73 injuries and 57/516 patients (11% with intra-abdominal injury. Urinalysis was positive for urobilinogen in 28/516 (5.4% patients, urine bilirubin in 15/516 (2.9% patients and urine hemoglobin in 313/516 (61% patients. Nineteen/forty-seven (4% subjects had liver lacerations, 28/56 (5% splenic lacerations, and 15/5 (3% bowel or mesenteric injury. Comparing the proportion of patients that had urobilinogen detected in the group with and without intra-abdominal injury, 8/28 (29% subjects with urobilinogen, 5/15 (33% subjects with bilirubin and 47/313 (15% subjects with urine hemoglobin were found to have liver lacerations, spleen lacerations, or bowel/mesenteric injuries. Preexisting liver or biliary conditions were not statistically associated with elevation of urine bilirubin, urine hemoglobin or urobilinogen on initial urinalysis after blunt abdominal trauma. Point prevalence for urobilinogen, urine bilirubin and urine hemoglobin are 5.43% (28/516, 2.91% (15/516 and 60.7% (313/516 respectively.CONCLUSIONS: The utility of the initial routine urinalysis in the ED for adult blunt abdominal trauma patients should not be used as a screening tool for the evaluation of intra

Analysis of urobilinogen and urine bilirubin for intra-abdominal injury in blunt trauma patients.

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Gorchynski, Julie; Dean, Kevin; Anderson, Craig L

2009-05-01

To determine the point prevalence of urine bilirubin, urine hemoglobin and urobilinogen in blunt trauma patients, and to evaluate its utility as a screening tool for intra-abdominal injury. Data analysis of 986 consecutive trauma patients of which 698 were adult blunt trauma patients. Five-hundred sixteen subjects had a urinalysis and a CT scan of the abdomen/pelvis or exploratory laparotomy. We reviewed initial urinalysis results from trauma patients in the emergency department (ED) for the presence of urine hemoglobin, uroblinogen and urine bilirubin. Computed tomography (CT) scan results and operative reports were reviewed from the trauma registry for evidence of liver laceration, spleen laceration, bowel or mesenteric injuries. There were 73 injuries and 57/516 patients (11%) with intra-abdominal injury. Urinalysis was positive for urobilinogen in 28/516 (5.4%) patients, urine bilirubin in 15/516 (2.9%) patients and urine hemoglobin in 313/516 (61%) patients. Nineteen/forty-seven (4%) subjects had liver lacerations, 28/56 (5%) splenic lacerations, and 15/5 (3%) bowel or mesenteric injury. Comparing the proportion of patients that had urobilinogen detected in the group with and without intra-abdominal injury, 8/28 (29%) subjects with urobilinogen, 5/15 (33%) subjects with bilirubin and 47/313 (15%) subjects with urine hemoglobin were found to have liver lacerations, spleen lacerations, or bowel/mesenteric injuries. Preexisting liver or biliary conditions were not statistically associated with elevation of urine bilirubin, urine hemoglobin or urobilinogen on initial urinalysis after blunt abdominal trauma. Point prevalence for urobilinogen, urine bilirubin and urine hemoglobin are 5.43% (28/516), 2.91% (15/516) and 60.7% (313/516) respectively. The utility of the initial routine urinalysis in the ED for adult blunt abdominal trauma patients should not be used as a screening tool for the evaluation of intra-abdominal injury.

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

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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…

Studies on the kinetics of unconjugated [14C]bilirubin metabolism in normal subjects and patients with compensated cirrhosis

International Nuclear Information System (INIS)

Owens, D.; Jones, E.A.; Carson, E.R.

1977-01-01

The kinetics of unconjugated 14 C-bilirubin metabolism have been investigated and analysed in terms of a three-pool model in a group of seven normal subjects and in a group of eight cirrhotic patients who had appreciable impairment of liver cell function. The results indicate that, in patients with compensated cirrhosis, the efficiency of the liver in extracting unconjugated bilirubin from plasma against a concentration gradient is impaired, even though the liver's capacity to conjugate bilirubin may be normal. As a consequence of the increased volume of distribution, the absolute hepatic clearance of unconjugated bilirubin is relatively well maintained. (author)

Pulse radiolysis investigations on the oxidation of bilirubin by chlorinated peroxyl radicals (Preprint No. RC.18)

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Mohan, Hari; Gopinathan, C.

1989-01-01

Chlorinated peroxyl radicals were observed to oxidize bilirubin. The rate constants, estimated from the formation kinetics of bilirubin cation, were observed to decrease with decrease in the chlorine substitution of various chlorinated peroxyl radicals. (author)

Significance of change in serum bilirubin in predicting left ventricular reverse remodeling and outcomes in heart failure patients with cardiac resynchronization therapy.

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Hosoda, Junya; Ishikawa, Toshiyuki; Matsumoto, Katsumi; Iguchi, Kohei; Matsushita, Hirooki; Ogino, Yutaka; Taguchi, Yuka; Sugano, Teruyasu; Ishigami, Tomoaki; Kimura, Kazuo; Tamura, Kouichi

2017-11-01

Research on the correlation of serum bilirubin level with cardiac function as well as outcomes in heart failure patients with cardiac resynchronization therapy (CRT) has not yet been reported. The aim of this study was to analyze the relationship between change in serum bilirubin level and left ventricular reverse remodeling, and also to clarify the impact of bilirubin change on clinical outcomes in CRT patients. We evaluated 105 consecutive patients who underwent CRT. Patients who had no serum total-bilirubin data at both baseline and 3-9 months' follow-up or had died less than 3 months after CRT implantation were excluded. Accordingly, a total of 69 patients were included in the present analysis. The patients were divided into two groups: decreased bilirubin group (serum total-bilirubin level at follow-up≤that at baseline; n=48) and increased bilirubin group (serum total-bilirubin level at follow-up>that at baseline; n=21). Mean follow-up period was 39.3 months. In the decreased bilirubin group, mean left ventricular end-systolic diameter decreased from 54.5mm to 50.2mm (p=0.001) and mean left ventricular ejection fraction increased significantly from 29.8% to 37.0% (p=0.001). In the increased bilirubin group, there was no significant change in echocardiographic parameters from baseline to follow-up. In Kaplan-Meyer analysis, cardiac mortality combined with heart failure hospitalization in the increased bilirubin group was significantly higher than that in the decreased bilirubin group (log-rank p=0.018). Multivariate Cox regression analysis revealed that increased bilirubin was an independent predictor of cardiac mortality combined with heart failure hospitalization (OR=2.66, p=0.023). The change in serum bilirubin is useful for assessment of left ventricular reverse remodeling and prediction of outcomes in heart failure patients with CRT. Copyright © 2017 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Association Of Serum Total Bilirubin Level With Diabetic Retinopathy In Type 2 Diabetes Mellitus.

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Ghaffar, Tahir; Marwat, Zahid Irfan; Ullah, Fahim; Khan, Salman; Hassan Aamir, Aziz Ul

2016-01-01

Serum bilirubin has anti-inflammatory, antioxidant and immunological properties. It is considered a protective substance against atherosclerotic and microvascular complications of diabetes mellitus (DM). This study was designed to find the association between total serum bilirubin concentration and diabetic retinopathy (DR). This case control study was conducted in the Department of Endocrinology, Diabetes and Metabolic Diseases, Hayatabad Medical Complex, Peshawar. Type-2 DM patients more than 18 years of age of either gender with duration of T2DM more than 6 months were included and sub categorized in two groups. Cases (DM with DR) and Controls (DM without DR) while patients with acute and chronic liver diseases, haemolytic anaemia, history of chronic alcohol consumption, use of hepatotoxic drugs (anti-tuberculous, anti-epileptic), women on oral contraceptive pills were excluded. All participants underwent ophthalmic examination at diabetic retinopathy screening clinic followed by pre designed set of investigations. A total of 152 patients, 76 cases and 76 controls were included. Serum bilirubin concentration was found inversely and independently (p 0.000) associated and inversely co related (r -0.345and p 0.000) with prevalence of DR. Cases were concentrated in the lower quartiles of serum bilirubin concentration and vice versa. Low haemoglobin (p 0.00) and longer duration of DM (0.003) were independently and directly associated with prevalence of DR. Serum bilirubin concentration is inversely and independently associated and inversely correlated with the prevalence of DR and may predict progression of DR over time.

The influence of bilirubin, haemolysis and turbidity on 20 analytical tests performed on automatic analysers. Results of an interlaboratory study.

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Grafmeyer, D; Bondon, M; Manchon, M; Levillain, P

1995-01-01

The director of a laboratory has to be sure to give out reliable results for routine tests on automatic analysers regardless of the clinical context. However, he may find hyperbilirubinaemia in some circumstances, parenteral nutrition causing turbidity in others, and haemolysis occurring if sampling is difficult. For this reason, the Commission for Instrumentation of the Société Française de Biologie Clinique (SFBC) (president Alain Feuillu) decided to look into "visible" interferences--bilirubin, haemolysis and turbidity--and their effect on 20 major tests: 13 substrates/chemistries: albumin, calcium, cholesterol, creatinine, glucose, iron, magnesium, phosphorus, total bilirubin, total proteins, triacylglycerols, uric acid, urea, and 7 enzymatic activities: alkaline phosphatase, alanine aminotransferase, alpha-amylase, aspartate aminotransferase, creatine kinase, gamma-glutamyl transferase and lactate dehydrogenase measured on 15 automatic analysers representative of those found on the French market (Astra 8, AU 510, AU 5010, AU 5000, Chem 1, CX 7, Dax 72, Dimension, Ektachem, Hitachi 717, Hitachi 737, Hitachi 747, Monarch, Open 30, Paramax, Wako 30 R) and to see how much they affect the accuracy of results under routine conditions in the laboratory. The study was carried out following the SFBC protocol for the validation of techniques using spiked plasma pools with bilirubin, ditauro-bilirubin, haemoglobin (from haemolysate) and Intralipid (turbidity). Overall, the following results were obtained: haemolysis affects tests the most often (34.5% of cases); total bilirubin interferes in 21.7% of cases; direct bilirubin and turbidity seem to interfere less at around 17%. The different tests are not affected to the same extent; enzyme activity is hardly affected at all; on the other hand certain major tests are extremely sensitive, increasingly so as we go through the following: creatinine (interference of bilirubin), triacylglycerols (interference of bilirubin and

Evaluation of 99mTc-Mercaptoacetyltriglycine-Biocytin as a new hepatobiliary imaging agent in mice coinjected with bilirubin

International Nuclear Information System (INIS)

Kim, Meyoung-kon; Seidel, Juergen; Le Nhat; Kim, In-Sook; Yoo, Tae-Moo; Barker, Craig; Kobayashi, Hisataka; Green, Michael V.; Carrasquillo, Jorge A.; Paik, Chang H.

1999-01-01

We evaluated 99m Tc-labeled mercaptoacetyltriglycine ( 99m Tc-MAG3)-biocytin as a hepatobiliary imaging agent in the absence and presence of bilirubin in mice. We then compared its pharmacokinetic parameters; peak liver/heart activity ratio (r max ) and half clearance time (HCT) with those of 99m Tc-labeled diisopropyl-iminodiacetic acid ( 99m Tc-disofenin). Balb/c mice were injected intravenously with hepatobiliary agent ( 99m Tc-MAG3-biocytin or 99m Tc-disofenin) alone or in combination with bilirubin at two doses (7 and 14 mg/kg) dissolved in 5% human serum albumin. Images were acquired every 15 s for 30 min with a gamma-camera equipped with a pinhole collimator. Dynamic images showed rapid hepatic uptake of 99m Tc-MAG3-biocytin, with rapid clearance from the blood and rapid excretion via the biliary system. Its hepatic uptake was not affected by bilirubin coinjection, whereas 99m Tc-disofenin coinjected with bilirubin showed a higher blood background than 99m Tc-disofenin alone. These qualitative findings were reflected in pharmacokinetic parameters, r max and HCT. The r max was obtained from plots of time versus liver/heart activity ratios obtained in equal-area regions of interest over the heart and liver. The HCT was calculated from the hepatic clearance curve from plots of time versus liver activity. 99m Tc-MAG3-biocytin without bilirubin coinjection showed an r max of 8.9±1.3 and an HCT of 399±36 s. These values did not change even when 14 mg/kg of bilirubin were coinjected. By contrast, the parameters for 99m Tc-disofenin with bilirubin were significantly (p max was decreased from 7.9±2.5 to 1.4±0.2 and HCT was increased from 292±32 s to 782±133 s. 99m Tc-MAG3-biocytin hepatobiliary scintigraphy in mice is not affected by bilirubin coinjection, and this hepatobiliary agent appears to offer promise for estimating hepatic function in patients with high bilirubin levels

Electrochemical Sensor for Bilirubin Detection Using Screen Printed Electrodes Functionalized with Carbon Nanotubes and Graphene

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Madasamy Thangamuthu

2018-03-01

Full Text Available Practice oriented point-of-care diagnostics require easy-to-handle, miniaturized, and low-cost analytical tools. In a novel approach, screen printed carbon electrodes (SPEs, which were functionalized with nanomaterials, are employed for selective measurements of bilirubin, which is an important biomarker for jaundice. Multi-walled carbon nanotubes (MWCNT and graphene separately deposited on SPEs provide the core of an electrochemical sensor for bilirubin. The electrocatalytic activity towards bilirubin oxidation (bilirubin to biliverdin was observed at +0.25 V. In addition, a further peak corresponding to the electrochemical conversion of biliverdin into purpurin appeared at +0.48 V. When compared to MWCNT, the graphene type shows a 3-fold lower detection limit (0.3 ± 0.022 nM and 0.1 ± 0.018 nM, respectively, moreover, the graphene type exhibits a larger linear range (0.1–600 µM than MWCNT (0.5–500 µM with a two-fold better sensitivity, i.e., 30 nA µM−1 cm−2, and 15 nA µM−1 cm−2, respectively. The viability is validated through measurements of bilirubin in blood serum samples and the selectivity is ensured by inhibiting common interfering biological substrates using an ionic nafion membrane. The presented approach enables the design and implementation of low cost and miniaturized electrochemical sensors.

Electrochemical Sensor for Bilirubin Detection Using Screen Printed Electrodes Functionalized with Carbon Nanotubes and Graphene.

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Thangamuthu, Madasamy; Gabriel, Willimann Eric; Santschi, Christian; Martin, Olivier J F

2018-03-07

Practice oriented point-of-care diagnostics require easy-to-handle, miniaturized, and low-cost analytical tools. In a novel approach, screen printed carbon electrodes (SPEs), which were functionalized with nanomaterials, are employed for selective measurements of bilirubin, which is an important biomarker for jaundice. Multi-walled carbon nanotubes (MWCNT) and graphene separately deposited on SPEs provide the core of an electrochemical sensor for bilirubin. The electrocatalytic activity towards bilirubin oxidation (bilirubin to biliverdin) was observed at +0.25 V. In addition, a further peak corresponding to the electrochemical conversion of biliverdin into purpurin appeared at +0.48 V. When compared to MWCNT, the graphene type shows a 3-fold lower detection limit (0.3 ± 0.022 nM and 0.1 ± 0.018 nM, respectively), moreover, the graphene type exhibits a larger linear range (0.1-600 µM) than MWCNT (0.5-500 µM) with a two-fold better sensitivity, i.e., 30 nA µM -1 cm -2 , and 15 nA µM -1 cm -2 , respectively. The viability is validated through measurements of bilirubin in blood serum samples and the selectivity is ensured by inhibiting common interfering biological substrates using an ionic nafion membrane. The presented approach enables the design and implementation of low cost and miniaturized electrochemical sensors.

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

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

2016-02-28

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. 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. 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. Higher serum direct bilirubin concentration was associated with the increased risk of LNM and poor prognosis in our rectal cancers.

Antioxidant status of serum bilirubin and uric acid in patients with polymyositis and dermatomyositis.

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Chen, Zhibo; Su, Zhongqian; Pang, Wanhui; Huang, Yuanyuan; Lin, Jie; Ding, Zhangna; Wu, Senmin; Xu, Shunyao; Quan, Weiwei; Zheng, Juzeng; Chen, Huale; Li, Zhengzheng; Li, Xiang; Li, Jia; Weng, Yiyun; Zhang, Xu

2017-07-01

Oxidative stress and variations in antioxidant status are implicated in the pathogenesis of inflammatory and autoimmune diseases. Polymyositis and dermatomyositis (PM/DM) are autoimmune diseases with inflammatory cells infiltrating into skeletal muscles, and the antioxidant status is still controversial. The aim of our study was to investigate the correlation between PM/DM and the antioxidant status of serum bilirubin (Tbil, Dbil and Ibil) and uric acid (UA). We measured serum concentrations of bilirubin (Tbil, Dbil and Ibil) and uric acid in 384 individuals, including 110 PM/DM patients and 274 healthy controls. We found that PM/DM patients had significantly lower serum concentrations of bilirubin (Tbil and Ibil) and uric acid than healthy controls, whether male or female. Also, after separately adjusting the covariances of age and gender, Tbil, Dbil, Ibil and UA were all relevant factors for PM/DM. Moreover, there were no significant differences in serum antioxidant molecule levels between PM and DM subgroups. Our study demonstrated the low serum levels of bilirubin and uric acid in patients with PM/DM. This suggested low antioxidant status in PM/DM patients with excessive oxidative stress.

Evaluation of bilirubin interference and accuracy of six creatinine assays compared with isotope dilution-liquid chromatography mass spectrometry.

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Nah, Hyunjin; Lee, Sang-Guk; Lee, Kyeong-Seob; Won, Jae-Hee; Kim, Hyun Ok; Kim, Jeong-Ho

2016-02-01

The aim of this study was to estimate bilirubin interference and accuracy of six routine methods for measuring creatinine compared with isotope dilution-liquid chromatography mass spectrometry (ID-LC/MS). A total of 40 clinical serum samples from 31 patients with serum total bilirubin concentration >68.4μmol/L were collected. Serum creatinine was measured using two enzymatic reagents and four Jaffe reagents as well as ID-LC/MS. Correlations between bilirubin concentration and percent difference in creatinine compared with ID-LC/MS were analyzed to investigate bilirubin interference. Bias estimations between the six reagents and ID-LC/MS were performed. Recovery tests using National Institute of Standards and Technology (NIST) Standard Reference Material (SRM) 967a were also performed. Both the enzymatic methods showed no bilirubin interference. However, three of the four Jaffe methods demonstrated significant bilirubin concentration-dependent interference in samples with creatinine levels creatinine levels ranging from 53.0 to 97.2μmol/L. Comparison of these methods with ID-LC/MS using patients' samples with elevated bilirubin revealed that the tested methods failed to achieve the bias goal at especially low levels of creatinine. In addition, recovery test using NIST SRM 967a showed that bias in one Jaffe method and two enzymatic methods did not achieve the bias goal at either low or high level of creatinine, indicating they had calibration bias. One enzymatic method failed to achieve all the bias goals in both comparison experiment and recovery test. It is important to understand that both bilirubin interference and calibration traceability to ID-LC/MS should be considered to improve the accuracy of creatinine measurement. Copyright © 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Association of serum total bilirubin level with diabetic retinopathy in type 2 diabetes mellitus

International Nuclear Information System (INIS)

Ghaffar, T.; Khan, S.; Aamir, A.U.H.; Marwat, Z.I.

2016-01-01

Serum bilirubin has anti-inflammatory, antioxidant and immunological properties. It is considered a protective substance against atherosclerotic and microvascular complications of diabetes mellitus (DM). This study was designed to find the association between total serum bilirubin concentration and diabetic retinopathy (DR). Methods: This case control study was conducted in the Department of Endocrinology, Diabetes and Metabolic Diseases, Hayatabad Medical Complex, Peshawar. Type-2 DM patients more than 18 years of age of either gender with duration of T2DM more than 6 months were included and sub categorized in two groups. Cases (DM with DR) and Controls (DM without DR) while patients with acute and chronic liver diseases, haemolytic anaemia, history of chronic alcohol consumption, use of hepatotoxic drugs (anti-tuberculous, anti-epileptic), women on oral contraceptive pills were excluded. All participants underwent ophthalmic examination at diabetic retinopathy screening clinic followed by pre designed set of investigations. Results: A total of 152 patients, 76 cases and 76 controls were included. Serum bilirubin concentration was found inversely and independently (p 0.000) associated and inversely co related (r -0.345 and p 0.000) with prevalence of DR. Cases were concentrated in the lower quartiles of serum bilirubin concentration and vice versa. Low haemoglobin (p 0.00) and longer duration of DM (0.003) were independently and directly associated with prevalence of DR. Conclusion: Serum bilirubin concentration is inversely and independently associated and inversely correlated with the prevalence of DR and may predict progression of DR over time. (author)

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

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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.

Persistent high serum bilirubin level after percutaneous transhepatic biliary drainage: analysis of 32 cases

International Nuclear Information System (INIS)

Choo, In Wook; Choi, Byung Ihn; Park, Jae Hyung; Han, Man Chung; Kim, Chu Wan

1986-01-01

The aim of percutaneous transhepatic biliary drainage (PTBD) is to decrease serum bilirubin level and promote liver function in patient with biliary tract disease, especially obstruction by malignant disease. But some patients showed persistent high serum bilirubin level or higher than pre-PTBD level. Percutaneous transhepatic biliary drainage was performed in 341 patients of obstructive jaundice for 5 years form July, 1981 to July, 1986 at department of radiology, Seoul National University Hospital. Follow up check of the serum bilirubin level was possible in 188 patients. Among them the authors analysed 32 patients who showed persistent high serum bilirubin level after PTBD. The results were as follows: 1. The male to female ratio was 3.4:1 and the age ranged from 33 to 75. 2. The causes of obstructive jaundice included 30 malignant diseases and 2 benign diseases. Malignant disease were 16 cases of bile duct carcinoma, 7 cases of pancreatic cancer and 7 cases of metastasis from stomach, colon and uterine cervix. Benign disease were 1 case of common hepatic duct stone and 1 case of intrahepatic duct stones. 3. The most common level of obstruction was trifurcation in 17 cases. 4. The most common indication of PTBD was palliative drainage of obstruction secondary to malignant tumor in 28 cases. 5. Change of serum bilirubin level ratio (post-PTBD level/pre-PTBD level) was 1.28, 1.22, 1.38, 1.51 in serial period of 1-3 days, 4-6 days, 1-2 week 2-3 week after PTBD. 6. Causes of persistent high serum bilirubin level after PTBD were 12 cases of partial drainage of intrahepatic bile, 13 cases of hepatic dysfunction including 9 cases of metastatic nodule, 2 cases of biliary cirrhosis, 2 cases of multiple liver abscess, and 7 cases of poor function of catheter including 4 cases of hemobilia, 1 case of multiple intrahepatic stones, pyobilia and intrahepatic Clonorchis sinensis.

Persistent high serum bilirubin level after percutaneous transhepatic biliary drainage: analysis of 32 cases

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Choo, In Wook; Choi, Byung Ihn; Park, Jae Hyung; Han, Man Chung; Kim, Chu Wan [Seoul National University College of Medicine, Seoul (Korea, Republic of)

1986-12-15

The aim of percutaneous transhepatic biliary drainage (PTBD) is to decrease serum bilirubin level and promote liver function in patient with biliary tract disease, especially obstruction by malignant disease. But some patients showed persistent high serum bilirubin level or higher than pre-PTBD level. Percutaneous transhepatic biliary drainage was performed in 341 patients of obstructive jaundice for 5 years form July, 1981 to July, 1986 at department of radiology, Seoul National University Hospital. Follow up check of the serum bilirubin level was possible in 188 patients. Among them the authors analysed 32 patients who showed persistent high serum bilirubin level after PTBD. The results were as follows: 1. The male to female ratio was 3.4:1 and the age ranged from 33 to 75. 2. The causes of obstructive jaundice included 30 malignant diseases and 2 benign diseases. Malignant disease were 16 cases of bile duct carcinoma, 7 cases of pancreatic cancer and 7 cases of metastasis from stomach, colon and uterine cervix. Benign disease were 1 case of common hepatic duct stone and 1 case of intrahepatic duct stones. 3. The most common level of obstruction was trifurcation in 17 cases. 4. The most common indication of PTBD was palliative drainage of obstruction secondary to malignant tumor in 28 cases. 5. Change of serum bilirubin level ratio (post-PTBD level/pre-PTBD level) was 1.28, 1.22, 1.38, 1.51 in serial period of 1-3 days, 4-6 days, 1-2 week 2-3 week after PTBD. 6. Causes of persistent high serum bilirubin level after PTBD were 12 cases of partial drainage of intrahepatic bile, 13 cases of hepatic dysfunction including 9 cases of metastatic nodule, 2 cases of biliary cirrhosis, 2 cases of multiple liver abscess, and 7 cases of poor function of catheter including 4 cases of hemobilia, 1 case of multiple intrahepatic stones, pyobilia and intrahepatic Clonorchis sinensis.

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

Science.gov (United States)

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.

Increased large VLDL and small LDL particles are related to lower bilirubin in Type 2 diabetes mellitus

NARCIS (Netherlands)

Dullaart, Robin P F; de Vries, Rindert; Lefrandt, Joop D

2014-01-01

OBJECTIVES: Bilirubin may protect against atherosclerotic cardiovascular disease by virtue of its anti-oxidative properties, but lower bilirubin may also be associated to atherogenic lipoprotein abnormalities. We determined associations of plasma (apo)lipoproteins and lipoprotein subfractions in

Operational impact of using a vanadate oxidase method for direct bilirubin measurements at an academic medical center clinical laboratory

Directory of Open Access Journals (Sweden)

Neha Dhungana

2017-08-01

Full Text Available Objectives: The aim of this study was to compare the operational impact of using vanadate oxidase versus diazo direct bilirubin assays for an academic medical center patient population. Design and methods: Retrospective study was done over an approximately 3.5 year period. The main automated chemistry instrumentation was a Roche Diagnostics cobas 8000 line. The Roche Direct Bilirubin assay was compared to Diazyme Laboratories Direct Bilirubin Assay and Randox Laboratories Direct Bilirubin assay using manufacturer's guidelines for hemolysis index, lipemia index, and analytical measurement range (AMR. Results: Retrospective data was analyzed for 47,333 serum/plasma specimens that had clinical orders for direct bilirubin. A total of 5943 specimens (12.6% exceeded the hemolysis index limit for the Roche method compared to only 0.2% and 0.05% of specimens for the Diazyme and Randox methods, respectively. The impact was particularly large on patients less than 2 years old, for which 51.3% of specimens exceeded the hemolysis index for the Roche method. A total of 1671 specimens (3.5% exceeded the lipemia index limit for the Roche method compared to less than 0.1% for the Randox method. Lastly, 988 (2.1% of specimens had direct bilirubin concentrations exceeding the upper AMR limit of 10 mg/dL [171 µmol/L] for the Roche assay compared to less than 1% of specimens for the vanadate oxidase methods. Conclusions: Vanadate oxidase direct bilirubin methods offer advantages over diazo methods in terms of less interference by hemolysis and lipemia, as well as wider AMR. The advantages are particularly evident for neonatal and infant populations. Keywords: Bilirubin, Clinical chemistry tests, Hemolysis, Hyperlipidemias, Jaundice, Photometry

Surface modifying of microporous PTFE capillary for bilirubin removing from human plasma and its blood compatibility

International Nuclear Information System (INIS)

Jin Gu; Yao Qizhi; Zhang Shanzi; Zhang Lei

2008-01-01

In this study, human serum albumin (HSA) was covalently immobilized onto the inner surface of microporous poly(tetrafluoroethylene) (MPTFE) capillaries for direct bilirubin removal from human plasma. To obtain active binding sites for HSA, the MPTFE capillaries were chemically functionalized by using a coating of poly(vinyl alcohol) (PVA)-glycidyl methacrylate (GMA) copolymers. Characterization of grafted MPTFE capillaries was verified by XPS, Fourier transform infrared spectroscopy (FT-IR), scanning electronic microscopy (SEM). Non-specific adsorption on the PVA-GMA coated capillary remains low (< 0.38 mg bilirubin/g), and higher affinity adsorption capacity, of up to 73.6 mg bilirubin/g polymer was obtained after HSA is immobilized. Blood compatibility of the grafted MPTFE capillary was evaluated by SEM and platelet rich plasma (PRP) contacting experiments. The experimental data on blood compatibility indicated that PVA-coated and PVA-GMA-HSA coated PTFE capillary showed a sharp suppress on platelets adhesion. The proposed method has the potential of serving in bilirubin removal in clinical application

Bilirubin exposure is associated with neonatal sepsis in the eight days preceding symptoms: a retrospective study.

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Raimondi, Francesco; Borrelli, Angela Carla; Ferrara, Teresa; Giannattasio, Antonietta; Capasso, Letizia

2017-09-01

To compare levels of bilirubin (using the area under the curve, AUC) in preterm infants before the onset of sepsis with healthy matched-controls. Preterm infants born between January 2011 and December 2015 with late-onset sepsis were enrolled in our retrospective study and were matched with healthy controls (sex, birth weight and gestational age). Levels of bilirubin were registered in the eight days preceding the onset of sepsis and the AUC was calculated for both groups. Eighty-eight neonates (44 cases) were studied. GA and BW did not differ between cases and controls. In cases, we found a higher value of AUC (30.7 versus 22.5; p = 0.021). In our retrospective cohort, we found that the levels of bilirubin and the AUC in the first eight days before the onset of sepsis in preterm infants were significantly higher than the healthy controls. These data suggest that the prolonged exposition to high levels of bilirubin could increase the infection susceptibility in preterm infants.

The lowering of bilirubin levels in patients with neonatal jaundice using massage therapy: A randomized, double-blind clinical trial.

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Eghbalian, Fatemeh; Rafienezhad, Haneyeh; Farmal, Javad

2017-11-01

Due to the effects of massage on various laboratory parameters (including those related to jaundice) in infants and the expansion of existing studies to achieve effective and safe therapy in the treatment of neonatal jaundice, this study aimed to investigate the effect of massage on bilirubin levels in cases of neonatal jaundice. In this study, 134 patients were randomly assigned to either an intervention group (massage combined with phototherapy, n=67) or a control group (phototherapy only, n=67). In both groups, serum total bilirubin level and frequency of daily bowel movements were measured and compared during each of the first four days of treatment. Baseline levels of bilirubin were similar between the two groups (P>0.05). During the measurements obtained post-intervention, significant differences surfaces between the two groups in bilirubin levels and frequency of daily bowel movements (Pmassage therapy between daily frequency of bowel movements and serum bilirubin level (P>0.05); this relationship became significant during the third and fourth days (PMassage therapy combined with phototherapy is an effective method for reducing serum total bilirubin in infants with neonatal jaundice. Copyright © 2017 Elsevier Inc. All rights reserved.

Bilirubin Increases Insulin Sensitivity in Leptin-Receptor Deficient and Diet-Induced Obese Mice Through Suppression of ER Stress and Chronic Inflammation

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Dong, Huansheng; Huang, Hu; Yun, Xinxu; Kim, Do-sung; Yue, Yinan; Wu, Hongju; Sutter, Alton; Chavin, Kenneth D.; Otterbein, Leo E.; Adams, David B.; Kim, Young-Bum

2014-01-01

Obesity-induced endoplasmic reticulum (ER) stress causes chronic inflammation in adipose tissue and steatosis in the liver, and eventually leads to insulin resistance and type 2 diabetes (T2D). The goal of this study was to understand the mechanisms by which administration of bilirubin, a powerful antioxidant, reduces hyperglycemia and ameliorates obesity in leptin-receptor-deficient (db/db) and diet-induced obese (DIO) mouse models. db/db or DIO mice were injected with bilirubin or vehicle ip. Blood glucose and body weight were measured. Activation of insulin-signaling pathways, expression of inflammatory cytokines, and ER stress markers were measured in skeletal muscle, adipose tissue, and liver of mice. Bilirubin administration significantly reduced hyperglycemia and increased insulin sensitivity in db/db mice. Bilirubin treatment increased protein kinase B (PKB/Akt) phosphorylation in skeletal muscle and suppressed expression of ER stress markers, including the 78-kDa glucose-regulated protein (GRP78), CCAAT/enhancer-binding protein (C/EBP) homologous protein, X box binding protein (XBP-1), and activating transcription factor 4 in db/db mice. In DIO mice, bilirubin treatment significantly reduced body weight and increased insulin sensitivity. Moreover, bilirubin suppressed macrophage infiltration and proinflammatory cytokine expression, including TNF-α, IL-1β, and monocyte chemoattractant protein-1, in adipose tissue. In liver and adipose tissue of DIO mice, bilirubin ameliorated hepatic steatosis and reduced expression of GRP78 and C/EBP homologous protein. These results demonstrate that bilirubin administration improves hyperglycemia and obesity by increasing insulin sensitivity in both genetically engineered and DIO mice models. Bilirubin or bilirubin-increasing drugs might be useful as an insulin sensitizer for the treatment of obesity-induced insulin resistance and type 2 diabetes based on its profound anti-ER stress and antiinflammatory properties. PMID

Serum bilirubin concentrations and incident coronary heart disease risk among patients with type 2 diabetes: the Dongfeng-Tongji cohort.

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Wang, Jing; Wu, Xiaofen; Li, Yaru; Han, Xu; Hu, Hua; Wang, Fei; Yu, Caizheng; Li, Xiulou; Yang, Kun; Yuan, Jing; Yao, Ping; Miao, Xiaoping; Wei, Sheng; Wang, Youjie; Chen, Weihong; Liang, Yuan; Guo, Huan; Yang, Handong; Wu, Tangchun; Zhang, Xiaomin; He, Meian

2017-03-01

Elevated serum bilirubin levels are associated with decreased coronary heart disease (CHD) risk in cross-sectional studies among diabetic patients, but prospective evidence is limited. We investigated the relationship of serum bilirubin levels with incident CHD risk among type 2 diabetes patients. In a prospective study of 2918 type 2 diabetes embedded in the Dongfeng-Tongji cohort, serum total bilirubin (TBil), direct bilirubin (DBil), and indirect bilirubin (IBil) were measured at baseline. Cox proportional hazards models were used to examine the association between serum bilirubin levels and CHD risk. A total of 440 CHD cases were identified during 12,017 person-years of follow-up. Compared with extreme quartiles, the adjusted hazard ratio and 95% confidence interval of incident CHD were 0.74 (0.56-0.99) with P trend = 0.08 in IBil, while in TBil and DBil, the bilirubin-CHD associations were not significant. Moreover, serum TBil and IBil levels were interacted with drinking status on the risk of incident CHD (P interaction = 0.021 and 0.037, respectively), and the associations were evident in ever drinkers. In drinkers, when serum TBil or IBil concentrations increased 1 μmol/L, the CHD risk both decreased 6% (95% CIs 0.89-0.99 and 0.87-1.00, respectively). Serum IBil levels were marginally related to decreased incident CHD risk among type 2 diabetes. Drinking could potentially enhance the associations of serum TBil and DBil levels with incident CHD risk.

[Bilirubin in the early neonatal period. Is there a positive aspect of hyperbilirubinemia?--A medical hypothesis].

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Bervoets, K; Schlenzig, J S; Böhles, H

1994-05-10

The fact that almost all neonates exhibit a "physiological" jaundice, prompts the question whether bilirubin, usually exclusively considered a potentially toxic endproduct of the metabolism of heme, might not also have a positive task in the first days of life. A recently discovered property of bilirubin under in vitro conditions is its ability to combine with free oxygen radicals such as are produced in the oxidative metabolic processes of the neonate immediately following birth. In the present article, the concept of the anti-oxidative effect of bilirubin, and its translation to the early neonatal period is presented and discussed on the basis of a number of examples.

Post-test probability for neonatal hyperbilirubinemia based on umbilical cord blood bilirubin, direct antiglobulin test, and ABO compatibility results.

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Peeters, Bart; Geerts, Inge; Van Mullem, Mia; Micalessi, Isabel; Saegeman, Veroniek; Moerman, Jan

2016-05-01

Many hospitals opt for early postnatal discharge of newborns with a potential risk of readmission for neonatal hyperbilirubinemia. Assays/algorithms with the possibility to improve prediction of significant neonatal hyperbilirubinemia are needed to optimize screening protocols and safe discharge of neonates. This study investigated the predictive value of umbilical cord blood (UCB) testing for significant hyperbilirubinemia. Neonatal UCB bilirubin, UCB direct antiglobulin test (DAT), and blood group were determined, as well as the maternal blood group and the red blood cell antibody status. Moreover, in newborns with clinically apparent jaundice after visual assessment, plasma total bilirubin (TB) was measured. Clinical factors positively associated with UCB bilirubin were ABO incompatibility, positive DAT, presence of maternal red cell antibodies, alarming visual assessment and significant hyperbilirubinemia in the first 6 days of life. UCB bilirubin performed clinically well with an area under the receiver-operating characteristic curve (AUC) of 0.82 (95 % CI 0.80-0.84). The combined UCB bilirubin, DAT, and blood group analysis outperformed results of these parameters considered separately to detect significant hyperbilirubinemia and correlated exponentially with hyperbilirubinemia post-test probability. Post-test probabilities for neonatal hyperbilirubinemia can be calculated using exponential functions defined by UCB bilirubin, DAT, and ABO compatibility results. • The diagnostic value of the triad umbilical cord blood bilirubin measurement, direct antiglobulin testing and blood group analysis for neonatal hyperbilirubinemia remains unclear in literature. • Currently no guideline recommends screening for hyperbilirubinemia using umbilical cord blood. What is New: • Post-test probability for hyperbilirubinemia correlated exponentially with umbilical cord blood bilirubin in different risk groups defined by direct antiglobulin test and ABO blood group

Modulation of bilirubin neurotoxicity by the Abcb1 transporter in the Ugt1-/- lethal mouse model of neonatal hyperbilirubinemia.

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Bockor, Luka; Bortolussi, Giulia; Vodret, Simone; Iaconcig, Alessandra; Jašprová, Jana; Zelenka, Jaroslav; Vitek, Libor; Tiribelli, Claudio; Muro, Andrés F

2017-01-01

Moderate neonatal jaundice is the most common clinical condition during newborn life. However, a combination of factors may result in acute hyperbilirubinemia, placing infants at risk of developing bilirubin encephalopathy and death by kernicterus. While most risk factors are known, the mechanisms acting to reduce susceptibility to bilirubin neurotoxicity remain unclear. The presence of modifier genes modulating the risk of developing bilirubin-induced brain damage is increasingly being recognised. The Abcb1 and Abcc1 members of the ABC family of transporters have been suggested to have an active role in exporting unconjugated bilirubin from the central nervous system into plasma. However, their role in reducing the risk of developing neurological damage and death during neonatal development is still unknown.To this end, we mated Abcb1a/b-/- and Abcc1-/- strains with Ugt1-/- mice, which develop severe neonatal hyperbilirubinemia. While about 60% of Ugt1-/- mice survived after temporary phototherapy, all Abcb1a/b-/-/Ugt1-/- mice died before postnatal day 21, showing higher cerebellar levels of unconjugated bilirubin. Interestingly, Abcc1 role appeared to be less important.In the cerebellum of Ugt1-/- mice, hyperbilirubinemia induced the expression of Car and Pxr nuclear receptors, known regulators of genes involved in the genotoxic response.We demonstrated a critical role of Abcb1 in protecting the cerebellum from bilirubin toxicity during neonatal development, the most clinically relevant phase for human babies, providing further understanding of the mechanisms regulating bilirubin neurotoxicity in vivo. Pharmacological treatments aimed to increase Abcb1 and Abcc1 expression, could represent a therapeutic option to reduce the risk of bilirubin neurotoxicity. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Bilirubin Prevents Atherosclerotic Lesion Formation in Low-Density Lipoprotein Receptor-Deficient Mice by Inhibiting Endothelial VCAM-1 and ICAM-1 Signaling.

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Vogel, Megan E; Idelman, Gila; Konaniah, Eddy S; Zucker, Stephen D

2017-04-01

Numerous epidemiological studies support an inverse association between serum bilirubin levels and the incidence of cardiovascular disease; however, the mechanism(s) by which bilirubin may protect against atherosclerosis is undefined. The goals of the present investigations were to assess the ability of bilirubin to prevent atherosclerotic plaque formation in low-density lipoprotein receptor-deficient ( Ldlr -/- ) mice and elucidate the molecular processes underlying this effect. Bilirubin, at physiological concentrations (≤20 μmol/L), dose-dependently inhibits THP-1 monocyte migration across tumor necrosis factor α-activated human umbilical vein endothelial cell monolayers without altering leukocyte binding or cytokine production. A potent antioxidant, bilirubin effectively blocks the generation of cellular reactive oxygen species induced by the cross-linking of endothelial vascular cell adhesion molecule 1 (VCAM-1) or intercellular adhesion molecule 1 (ICAM-1). These findings were validated by treating cells with blocking antibodies or with specific inhibitors of VCAM-1 and ICAM-1 signaling. When administered to Ldlr -/- mice on a Western diet, bilirubin (30 mg/kg intraperitoneally) prevents atherosclerotic plaque formation, but does not alter circulating cholesterol or chemokine levels. Aortic roots from bilirubin-treated animals exhibit reduced lipid and collagen deposition, decreased infiltration of monocytes and lymphocytes, fewer smooth muscle cells, and diminished levels of chlorotyrosine and nitrotyrosine, without changes in VCAM-1 or ICAM-1 expression. Bilirubin suppresses atherosclerotic plaque formation in Ldlr -/- mice by disrupting endothelial VCAM-1- and ICAM-1-mediated leukocyte migration through the scavenging of reactive oxygen species signaling intermediaries. These findings suggest a potential mechanism for the apparent cardioprotective effects of bilirubin. © 2017 The Authors. Published on behalf of the American Heart Association, Inc

Kinetics of oxidation of bilirubin and its protein complex by hydrogen peroxide in aqueous solutions

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Solomonov, A. V.; Rumyantsev, E. V.; Antina, E. V.

2010-12-01

A comparative study of oxidation reactions of bilirubin and its complex with albumin was carried out in aqueous solutions under the action of hydrogen peroxide and molecular oxygen at different pH values. Free radical oxidation of the pigment in both free and bound forms at pH 7.4 was shown not to lead to the formation of biliverdin, but to be associated with the decomposition of the tetrapyrrole chromophore into monopyrrolic products. The effective and true rate constants of the reactions under study were determined. It was assumed that one possible mechanism of the oxidation reaction is associated with the interaction of peroxyl radicals and protons of the NH groups of bilirubin molecules at the limiting stage with the formation of a highly reactive radical intermediate. The binding of bilirubin with albumin was found to result in a considerable reduction in the rate of the oxidation reaction associated with the kinetic manifestation of the protein protection effect. It was found that the autoxidation of bilirubin by molecular oxygen with the formation of biliverdin at the intermediate stage can be observed with an increase in the pH of solutions.

Operational impact of using a vanadate oxidase method for direct bilirubin measurements at an academic medical center clinical laboratory.

Science.gov (United States)

Dhungana, Neha; Morris, Cory; Krasowski, Matthew D

2017-08-01

The aim of this study was to compare the operational impact of using vanadate oxidase versus diazo direct bilirubin assays for an academic medical center patient population. Retrospective study was done over an approximately 3.5 year period. The main automated chemistry instrumentation was a Roche Diagnostics cobas 8000 line. The Roche Direct Bilirubin assay was compared to Diazyme Laboratories Direct Bilirubin Assay and Randox Laboratories Direct Bilirubin assay using manufacturer's guidelines for hemolysis index, lipemia index, and analytical measurement range (AMR). Retrospective data was analyzed for 47,333 serum/plasma specimens that had clinical orders for direct bilirubin. A total of 5943 specimens (12.6%) exceeded the hemolysis index limit for the Roche method compared to only 0.2% and 0.05% of specimens for the Diazyme and Randox methods, respectively. The impact was particularly large on patients less than 2 years old, for which 51.3% of specimens exceeded the hemolysis index for the Roche method. A total of 1671 specimens (3.5%) exceeded the lipemia index limit for the Roche method compared to less than 0.1% for the Randox method. Lastly, 988 (2.1%) of specimens had direct bilirubin concentrations exceeding the upper AMR limit of 10 mg/dL [171 µmol/L] for the Roche assay compared to less than 1% of specimens for the vanadate oxidase methods. Vanadate oxidase direct bilirubin methods offer advantages over diazo methods in terms of less interference by hemolysis and lipemia, as well as wider AMR. The advantages are particularly evident for neonatal and infant populations.

Diagnostic value of blood urea and bilirubin levels determination in patients with gastroduodenal zone diseases

Directory of Open Access Journals (Sweden)

I. B. Zhakun

2017-12-01

Full Text Available The study of relationships of urea and bilirubin blood levels in patients with Helicobacter pylori associated gastroduodenal pathology (HP-aGDP has the considerable relevance for clinicians, since these indicators represent the status and function of the gastroduodenal zone. The aim of this study was to estimate changes of bilirubin and urea blood levels in patients with HP-aGDP before and after treatment. Materials and methods. Our study has included 59 patients of the main group with different HP-aGDP and 40 patients of the control group with community-acquired pneumonia (CAP. Results. In patients with HP-aGDP the doubly severe reduction of urea concentration was observed in significantly greater number of patients, while half of the patients in the controls had an increase of its level by 10.4 %. The bilirubin concentration decrease was more pronounced (37.1 % vs. 3.5 % and significant (p < 0.05 in patients with HP-aGDP. Its rate depended on the dynamics of urea exactly in patients with HP-aGDP and it was more pronounced in case of urea reduction (p < 0.05. Thus, the revealed association of bilirubin and urea levels changes, namely their decrease owing to the treatment, was inherent only to patients with HP-aGDP unlike to the patients with CAD. We also determined the involvement of lipid, carbohydrate and protein metabolism, electrolytes, composition of blood in the processes of local and systemic inflammation caused by HP and its relationship with adaptive reactions, which generally depended on other individual characteristics of patients in the study group (age, duration of disease, ulcer size, etc.. Conclusions. The monitoring of urea and bilirubin blood levels in patients especially with HP-aGDP during the eradication has a specific diagnostic and prognostic value. The bilirubin level in such cases reflects the severity of cholestasis, inflammatory lesions of the duodenal mucosa, comorbid hepatobiliary disease, while the urea level

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

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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

Bilirubin provides perforator flap protection from ischaemia-reperfusion injury in a rat model: a preliminary result.

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Kim, Sung Young; Rah, Dong Kyun; Chong, Yosep; Lee, Song Hyun; Park, Tae Hwan

2016-10-01

The use of bilirubin, a well-known and powerful antioxidant, has gained popularity in recent years because of its role in the prevention of ischaemic heart disease in patients with Gilbert's syndrome. We investigate the effects of bilirubin on ischaemia-reperfusion (I/R) injury using a rat perforator flap model. Forty-eight rats were randomly divided into two groups: experimental (bilirubin) group (n = 24) and control group (n = 24). In each group, elevated bilateral deep inferior epigastric perforator (DIEP) flaps were created. The right (no ischaemia side) and left (ischaemia side) DIEP flaps were separated according to the presence of ischaemia induction. Ischaemia was induced in anaesthetised rats by perforator clamping for 15 or 30 minutes. After surgery, the flap survival was assessed daily on postoperative days 0 to 5, and overall histological changes of DIEP flaps above the perforator were analysed at postoperative day 5. The flap survival rate in the bilirubin group was significantly higher than that in the control group at the ischaemia side following perforator clamping for 15 or 30 minutes (93·42 ± 4·48% versus 89·63 ± 3·98%, P = 0·002; and 83·96 ± 4·23% versus 36·46 ± 6·38%, P bilirubin was found to alleviate perforator flap necrosis caused by I/R injury in this experimental rat model. © 2015 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

DECREASED BILIRUBIN TRANSPORT IN THE PERFUSED LIVER OF ENDOTOXEMIC RATS

NARCIS (Netherlands)

ROELOFSEN, H; VANDERVEERE, CN; OTTENHOFF, R; SCHOEMAKER, B; JANSEN, PLM; ELFERINK, RPJO

1994-01-01

Background/Aims: Hyperbilirubinemia associated with sepsis is frequently observed in humans. In this study, an experimental rat model was developed to study bilirubin metabolism and transport during endotoxemia. Methods: Rats were injected intravenously with a single bolus of lipopolysaccharide (1

Bilirubin and beyond : A review of lipid status in Gilbert's syndrome and its relevance to cardiovascular disease protection

NARCIS (Netherlands)

Bulmer, A. C.; Verkade, H. J.; Wagner, K. -H.

Gilbert's syndrome (GS) is characterized by a benign, mildly elevated bilirubin concentration in the blood. Recent reports show clear protection from cardiovascular disease in this population. Protection of lipids, proteins and other macromolecules from oxidation by bilirubin represents the most

Decreased bilirubin transport in the perfused liver of endotoxemic rats

NARCIS (Netherlands)

Roelofsen, H.; van der Veere, C. N.; Ottenhoff, R.; Schoemaker, B.; Jansen, P. L.; Oude Elferink, R. P.

1994-01-01

Hyperbilirubinemia associated with sepsis is frequently observed in humans. In this study, an experimental rat model was developed to study bilirubin metabolism and transport during endotoxemia. Rats were injected intravenously with a single bolus of lipopolysaccharide (1 mg/kg); after 18 hours, the

The value of transcutaneous method of bilirubin measurement in newborn population with the risk of ABO hemolytic disease.

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Stoniene, Dalia; Buinauskiene, Jūrate; Markūniene, Egle

2009-01-01

OBJECTIVE OF THE STUDY. To evaluate the correlation between total serum bilirubin (TSB) and transcutaneous bilirubin (TcB) levels in newborn infants at risk of ABO hemolytic disease. MATERIAL AND METHODS. During a prospective study, 130 full-term (>or=37 weeks of gestation) newborn infants with diagnosed ABO blood group incompatibility were examined. TSB level was measured at the age of 6 hours; further measurements were performed at 24, 48, and 72 hours following the first measurement. Blood samples were collected from the peripheral veins. In clinical laboratory, total serum bilirubin level was measured using Jendrassik-Grof method. TcB level in the forehead was measured using a noninvasive bilirubinometer BiliCheck (SpectRX Inc, Norcross, GA) according to the manufacturer's instructions within +/-30 min after getting a blood sample. RESULTS. During the study, 387 double tests were performed to measure TSB and TcB levels. TSB level (114.83 [62.85] micromol/L) closely correlated with TcB level (111.51 [61.31] micromol/L) (r=0.92, Por=98 micromol/L, ABO hemolytic disease in newborns may be diagnosed with 100% sensitivity and 98% specificity; positive predictive value was 62% and negative predictive value was 100%. While a newborn's age increases, TcB sensitivity and specificity for diagnosing ABO hemolytic disease decrease. CONCLUSION. While evaluating bilirubin level transcutaneously according to nomograms of serum bilirubin level, the results should be considered with caution, especially for newborns with a risk of ABO hemolytic disease. The hour-specific nomograms of transcutaneous bilirubin level should be used to evaluate hyperbilirubinemia using only a noninvasive method.

Low antioxidant status of serum bilirubin, uric acid, albumin and creatinine in patients with myasthenia gravis.

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Yang, Dehao; Su, Zhongqian; Wu, Shengjie; Bi, Yong; Li, Xiang; Li, Jia; Lou, Kangliang; Zhang, Hongyu; Zhang, Xu

2016-12-01

Oxidative stress and low antioxidant status play a major role in the pathogenesis of inflammatory and autoimmune diseases. Myasthenia gravis (MG) is an autoimmune condition targeting the neuromuscular junction, and its antioxidant status is still controversial. Our study aimed to investigate the correlation between the clinical characteristics of MG and the serum antioxidant status of bilirubin (Tbil, Dbil and Ibil), uric acid, albumin and creatinine. We measured serum antioxidant molecule levels of bilirubin (Tbil, Dbil and Ibil), uric acid, albumin and creatinine in 380 individuals, including 166 MG and 214 healthy controls. We found that MG patients had significantly lower serum levels of bilirubin (Tbil, Dbil and Ibil), uric acid, albumin and creatinine than healthy controls, whether male or female. Moreover, it was also shown in our study that uric acid, albumin and creatinine levels in patients with MG were correlated with disease activity and classifications performed by the Myasthenia Gravis Foundation of America. Our findings demonstrated that serum levels of bilirubin (Tbil, Dbil and Ibil), uric acid, albumin and creatinine were reduced in patients with MG. This suggested an active oxidative process in MG patients who had low antioxidant status.

Increment of serum bilirubin as an independent marker predicting new-onset type 2 diabetes mellitus in a Korean population.

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Lee, S-E; Lee, Y-B; Jun, J E; Jin, S-M; Jee, J H; Bae, J C; Kim, J H

2017-03-01

Several cross-sectional studies reported that serum bilirubin concentrations had an inverse association with type 2 diabetes mellitus (T2DM) prevalence. The aim of the current study was to investigate the relationship between percentage change in bilirubin levels (PCB) and incident risk of T2DM using a longitudinal model. 22,084 participants who received regular health check-ups between 2006 and 2012 were enrolled. Multivariable-adjusted Cox regression models were used to determine the hazard ratio (HR) of incident T2DM based on PCB. PCB was determined by subtracting baseline serum bilirubin level (BB) from the bilirubin level at the end of follow-up or a year before the last date of diagnosis, dividing by BB and multiplying by 100. Compared to non-diabetics, BB was lower in the diabetic group at the initial visit. There were 20,098 participants without T2DM at the initial visit; 1253 new cases occurred during follow-up. As PCB increased, T2DM incidence also increased (P bilirubin level of the Incident T2DM group increased before T2DM development and decreased rapidly thereafter compared to others (P Bilirubin level increment over time is associated with T2DM development. Copyright © 2016 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

Mildly elevated serum total bilirubin levels are negatively associated with carotid atherosclerosis among elderly persons with type 2 diabetes.

Science.gov (United States)

Kawamoto, Ryuichi; Ninomiya, Daisuke; Hasegawa, Yoichi; Kasai, Yoshihisa; Kusunoki, Tomo; Ohtsuka, Nobuyuki; Kumagi, Teru; Abe, Masanori

2016-01-01

Diabetes is strongly associated with several mechanisms of tissue damage such as oxidative stress. Serum bilirubin may have a beneficial role in preventing oxidative changes in cardiovascular disease (CVD). Limited information is available on whether serum bilirubin is an independent confounding factor for carotid atherosclerosis among elderly persons with type 2 diabetes. The study subjects were 169 men aged 79 ± 8 (mean ± SD) years and 205 women aged 81 ± 8 years that were enrolled consecutively from patients in the medical department. Carotid intima-media thickness (IMT) and plaque were derived via B-mode ultrasonography. Multiple linear regression analysis showed that serum total bilirubin (β = -0.160) was significantly associated with carotid IMT. Compared to subjects with a serum total bilirubin of tertile-1 (0.13-0.58 mg/dL), the multivariate-adjusted odds ratio (95% confidence interval) of carotid IMT ≥1.0 mm including plaque and carotid plaque was 0.46 (0.23-0.93) and 0.32 (0.17-0.60) in the Tertile-3 group (0.87-1.93 mg/dL), respectively. Next, data were further stratified by gender, age, smoking status, medication and prevalence of CVD. There were no significant differences in serum total bilirubin levels between selected subgroups. Our data demonstrated a negative association between serum total bilirubin and carotid atherosclerosis among elderly persons with type 2 diabetes.

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

Energy Technology Data Exchange (ETDEWEB)

Abu-Bakar, A' edah, E-mail: a.abubakar@uq.edu.au [The University of Queensland, National Research Centre for Environmental Toxicology (Entox), 4072 Brisbane, Queensland (Australia); Arthur, Dionne Maioha [The University of Queensland, National Research Centre for Environmental Toxicology (Entox), 4072 Brisbane, Queensland (Australia); Cooperative Research Centre for Contamination Assessment and Remediation of the Environment, Adelaide (Australia); Aganovic, Simona [Department of Pharmaceutical Biosciences, Uppsala University, Biomedical Centre, Box 578, S-751 23 Uppsala (Sweden); Ng, Jack C. [The University of Queensland, National Research Centre for Environmental Toxicology (Entox), 4072 Brisbane, Queensland (Australia); Cooperative Research Centre for Contamination Assessment and Remediation of the Environment, Adelaide (Australia); Lang, Matti A. [The University of Queensland, National Research Centre for Environmental Toxicology (Entox), 4072 Brisbane, Queensland (Australia); Department of Pharmaceutical Biosciences, Uppsala University, Biomedical Centre, Box 578, S-751 23 Uppsala (Sweden)

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

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

International Nuclear Information System (INIS)

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

2011-01-01

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: ► CYP2A5 metabolizes bilirubin to biliverdin and dipyrroles. ► Bilirubin increased the hepatic CYP2A5 protein and activity levels. ► Bilirubin does not change the hepatic CYP2A5 mRNA levels. ► Co-treatment with a protein synthesis inhibitor

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

Science.gov (United States)

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 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

Cobinding of bilirubin and laurate to human serum albumin: spectroscopic characterization of stoichiometric complexes

DEFF Research Database (Denmark)

Honoré, B; Sato, H; Brodersen, R

1988-01-01

Light absorption and CD spectra of bound bilirubin and albumin fluorescence spectra have been recorded from mixtures containing albumin, A, bilirubin, B, and laurate, L, in Tris-NaCl buffer at pH 8.2, 25 degrees C. Concentrations of the corresponding stoichiometric complexes, ABiLj, for i = 0....../3 and j = 0/3, have been calculated from previously determined stoichiometric cobinding constants (H. Sato et al. (1988) Arch. Biochem. Biophys. 260, 811-821). Spectral data of the complexes have finally been found by iterative computer fitting using the principle of several acceptable solutions (R...

Mildly Elevated Serum Bilirubin Levels Are Negatively Associated with Carotid Atherosclerosis among Elderly Persons

Science.gov (United States)

Kawamoto, Ryuichi; Ninomiya, Daisuke; Hasegawa, Yoichi; Kasai, Yoshihisa; Kusunoki, Tomo; Ohtsuka, Nobuyuki; Kumagi, Teru; Abe, Masanori

2014-01-01

Serum bilirubin may have a beneficial role in preventing oxidative changes in atherosclerosis. Limited information is available on whether serum total bilirubin is an independent confounding factor for carotid atherosclerosis {for example, intima-media thickness (IMT), plaque} measured noninvasively by B-mode ultrasonography only among elderly persons. The study subjects were 325 men aged 79±8 (mean ± standard deviation) years and 509 women aged 81±8 years that were enrolled consecutively from patients aged ≥60 years in the medical department. Carotid IMT and plaque were derived via B-mode ultrasonography. Multiple linear regression analysis showed that in men age (β = 0.199, p = 0.002), smoking status (β = 0.154, p = 0.006), GGT (β = -0.139, p = 0.039), and GGT (β = -0.133, p = 0.022) were significantly and independently associated with carotid IMT, and in women age (β = 0.186, pbilirubin (β = -0.119, p = 0.006), and prevalence of cardiovascular disease (CVD) (β = 0.103, p = 0.017) were also independently associated with carotid IMT. The odds ratios (ORs) {95% confidence interval (CI)} of increasing serum bilirubin category were negatively associated with carotid IMT ≥1.0 mm and plaque in both genders. Compared to subjects with a serum bilirubin of Quartile-1, the multivariate-OR (95% CI) of carotid plaque was 0.25 (0.11–0.57) in the Quartile-4 male group, and 0.41 (0.21–0.78) in the Quartile-2 female group, 0.51 (0.26–0.98) in the Quartile-3 female group, and 0.46 (0.24–0.89) in the Quartile-4 female group. Our data demonstrated an independently negative association between serum bilirubin and carotid atherosclerosis in both genders. PMID:25479598

Oxidation reactions of bilirubin in aqueous solutions

International Nuclear Information System (INIS)

Mohan, Hari; Gopinathan, C.

1990-01-01

The radical cation of bilirubin (BR) has been tentatively identified as a transient intermediate in the reactions of BR with different oxidizing species such as Br 2 - , I 2 - and CH 3 I . OH. The rate constants for these reactions have been determined as 2.4 x 10 9 , l.0 x 10 9 and 2.7 x 10 9 dm 3 mol -1 s -1 , respectively. Biliverdin is likely to be among the stable products formed on oxidation of BR by these oxidizing species. (author)

Association between serum bilirubin levels and decline in estimated glomerular filtration rate among patients with type 2 diabetes.

Science.gov (United States)

Wang, Jing; Li, Yaru; Han, Xu; Hu, Hua; Wang, Fei; Yu, Caizheng; Li, Xiulou; Yang, Kun; Yuan, Jing; Yao, Ping; Miao, Xiaoping; Wei, Sheng; Wang, Youjie; Chen, Weihong; Liang, Yuan; Zhang, Xiaomin; Guo, Huan; Pan, An; Yang, Handong; Wu, Tangchun; He, Meian

2016-01-01

Studies indicate that elevated serum total bilirubin (TBil) levels are associated with lower risk of diabetic kidney disease (DKD). Few studies examined the associations of direct bilirubin (DBil) and indirect bilirubin (IBil) with the development of DKD. Type 2 diabetes patients (n=2,958) with estimated glomerular filtration (eGFR)≥60mlmin(-1) 1.73m(-2) from the Dongfeng-Tongji cohort were selected and followed up for 5years. Development of DKD was defined as decline in eGFR≥30% during follow-up. Generalize linear model was used to assess the associations of bilirubin levels with DKD development. Compared with those in the first tertile of serum TBil, the relative risks (RRs) and 95% confidence intervals (CIs) of incident eGFR decline for tertile 2 to 3 were 0.83 (0.64-1.09) and 0.74 (0.56-0.98), Ptrend=0.04. The counterpart RRs (95% CIs) in IBil were 0.74 (0.57-0.97) and 0.75 (0.57-0.98), Ptrend=0.04. No significant associations were observed in DBil. Moreover, TBil and IBil interacted with smoking, the bilirubin-DKD associations were evident in ever smokers. Our findings suggest that elevation of serum TBil or IBil levels are independent protective factors for development of DKD, particularly in smokers. Copyright © 2016 Elsevier Inc. All rights reserved.

Bile Gastritis Following Laparoscopic Single Anastomosis Gastric Bypass: Pilot Study to Assess Significance of Bilirubin Level in Gastric Aspirate.

Science.gov (United States)

Shenouda, Michael M; Harb, Shady ElGhazaly; Mikhail, Sameh A A; Mokhtar, Sherif M; Osman, Ayman M A; Wassef, Arsany T S; Rizkallah, Nayer N H; Milad, Nader M; Anis, Shady E; Nabil, Tamer Mohamed; Zaki, Nader Sh; Halepian, Antoine

2018-02-01

Laparoscopic single anastomosis gastric bypass (SAGB) is increasingly performed for morbidly obese patients. This pilot study aims primarily at evaluating the incidence of bile gastritis after SAGB. The occurrence of reflux oesophagitis and reflux symptoms were also assessed. This study included 20 patients having no reflux symptoms. All patients underwent a SAGB as a primary bariatric procedure by a single surgeon. Patients included consented to have an upper GI endoscopy done at 6 months postoperatively. Gastric aspirate was sent for bilirubin level assessment. Gastric and esophageal biopsies were submitted for histopathology and campylobacter-like organism (CLO) test. In our study, the rate of bile gastritis was 30%. In 18 patients, the level of bilirubin in gastric aspirate seems to be related to the degree of mucosal inflammation. The remaining two patients had microscopic moderate to severe gastritis with normal aspirate bilirubin level. Two patients with bilirubin level in aspirate more than 20 mg/dl had severe oesophagitis, gastritis with erosions, and metaplasia. Relationship between bilirubin level and histopathological findings of gastric biopsy examination was statistically significant with a P value of 0.001. The incidence of bile gastritis in this cohort is higher than reported in the literature, and this may be worrying. The correlation between endoscopic findings and patients' symptoms is poor. Bilirubin level and pH in aspirate might be useful tools to confirm alkaline reflux. Its level might help to choose candidates for revision surgery after SAGB. This needs further validation with larger sample size.

Bilirubin isomer distribution in jaundiced neonates during phototherapy with LED light centered at 497 nm (turquoise) vs. 459 nm (blue).

Science.gov (United States)

Ebbesen, Finn; Madsen, Poul H; Vandborg, Pernille K; Jakobsen, Lasse H; Trydal, Torleif; Vreman, Hendrik J

2016-10-01

Phototherapy using blue light is the treatment of choice worldwide for neonatal hyperbilirubinemia. However, treatment with turquoise light may be a desirable alternative. Therefore, the aim of this randomized, controlled study was to compare the bilirubin isomer distribution in serum of jaundiced neonates after 24 h of therapy with narrow-band (LED) light centered at 497 nm (turquoise) vs. 459 nm (blue), of essentially equal irradiance. Eighty-three neonates (≥33 wk gestational age) with uncomplicated hyperbilirubinemia were included in the study. Forty neonates were exposed to light centered at 497 nm and 43 infants with light centered at 459 nm. Irradiances were 5.2 × 10(15) and 5.1 × 10(15) photons/cm(2)/s, respectively. After 24 h of treatment no significant differences in serum concentrations of total bilirubin isomers and Z,Z-bilirubin were observed between the 2 groups. Interestingly, concentrations of Z,E-bilirubin, and thus also total bilirubin isomers formed during therapy, were highest for infants receiving light centered at 459 nm, while the concentration of E,Z-bilirubin was highest for those receiving light centered at 497 nm. No significant difference was found between concentrations of E,Z-lumirubin. Therapy with LED light centered at 497 nm vs. 459 nm, applied with equal irradiance on the infants, resulted in a different distribution of bilirubin isomers in serum.

Bilirubin levels determine vascular complications in diabetes mellitus type 2

Directory of Open Access Journals (Sweden)

Yu V Pankratova

2013-03-01

Full Text Available Реферат по материалам статьи Katsiki N, Karagiannis A, Mikhailidis DP. Diabetes, bilirubin and amputations: is there a link? Diabetologia. DOI 10.1007/s00125-013-2840-1

Structures of bilirubin conjugates synthesized in vitro from bilirubin and uridine diphosphate glucuronic acid, uridine diphosphate glucose or uridine diphosphate xylose by preparations from rat liver

NARCIS (Netherlands)

Fevery, J.; Leroy, P.; van de Vijver, M.; Heirwegh, K. P.

1972-01-01

1. In incubation mixtures containing digitonin-activated or untreated preparations from rat liver, albumin-solubilized bilirubin as the acceptor substrate and (a) UDP-glucuronic acid, (b) UDP-glucose or (c) UDP-xylose as the sugar donor, formation of the following ester glycosides was demonstrated:

Conformational changes in the bilirubin-human serum albumin complex at extreme alkaline pH

DEFF Research Database (Denmark)

Honoré, B; Frandsen, P C

1986-01-01

Light-absorption, c.d. and fluorescence of the bilirubin-albumin complex were investigated at extreme alkaline pH. Above pH 11.1 albumin binds the bilirubin molecule, twisted oppositely to the configuration at more neutral pH. On the basis of light-absorption it is shown that two alkaline...... transitions occur. The first alkaline transition takes place at pH between 11.3 and 11.8, co-operatively dissociating at least six protons. The second alkaline transition takes place at pH between 11.8 and 12.0. It probably implies a reversible unfolding of the albumin molecule, increasing the distance...

Direct antioxidant properties of bilirubin andbiliverdin. Is there a role for biliverdin reductase?

Directory of Open Access Journals (Sweden)

Thomas eJansen

2012-03-01

Full Text Available 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 reactive oxygen species. 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 RONS. 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 (CO, biliverdin/bilirubin, and the release of free iron with subsequent ferritin induction. With the present review we would like to highlight the important antioxidant role of the heme oxygenase system and especially discuss the contribution of the biliverdin, bilirubin and biliverdin reductase to these beneficial effects. The bilierdin reductase 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 biliverdin reductase, 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.

Total serum bilirubin levels and sensorineural hearing loss in the US adolescents: NHANES 2007-2010.

Science.gov (United States)

Zhou, Guoli; Fu, Wenjiang

2018-02-01

We aimed to investigate whether current levels of total serum bilirubin are associated with different subtypes of sensorineural hearing loss (SNHL) in adolescents. A set of cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) (2007-2010) was used. A subset of 1404 adolescents was sampled for measurements of total serum bilirubin, tympanometry, and average pure tone threshold at low-frequencies (LPTA: 500, 1000, 2000 Hz) or high-frequencies (HPTA: 3000, 4000, 6000, and 8000 Hz). SNHL was defined as the hearing loss that had type A tympanograms with a peak admittance of 0.3 ml or greater. Associations between serum bilirubin (square-root transformed) and different subtypes of SNHL were evaluated using binary or multinomial logistic regression models with 4-year sampling weights. The bootstrap method was used for estimation of variance and 10-fold cross-validation for assessment of overfitting issue. Total serum bilirubin levels were found to be associated with any high-frequency (HPTA>15 dB in at least one ear, adjusted odds-ratio (OR a )(bootstrap 95% confidence interval) = 3.29(1.31-8.19), p = 0.011), but not with any low-frequency (LPTA>15 dB in at least one ear), SNHL in the US adolescents. Furthermore, high-frequency SNHL with HPTA>15 dB in both ears (bilateral) or HPTA≥25 dB in at least one ear, compared to that with HPTA>15 dB in one ear only (unilateral) or HPTA = 15-25 dB in at least one ear, had a stronger association with total serum bilirubin levels (OR a  = 5.37(1.27-22.65), p = 0.022 for bilateral; OR a  = 2.64(0.84-8.25), p = 0.094 for unilateral; OR a  = 5.00(0.95-26.58), p = 0.058 for HPTA≥25 dB in at least one ear; as well as OR a  = 3.06(1.15-8.25), p = 0.025 for HPTA = 15-25 dB in at least one ear). No severe overfitting problems were found. Our findings suggest that current levels of total serum bilirubin may be informative in predicting and/or targeting high-frequency SNHL

Clinical value of serum bilirubin subfractionation by high-performance liquid chromatography and conventional methods in patients with primary biliary cirrhosis

NARCIS (Netherlands)

Jansen, P. L.; Peters, W. H.; Janssens, A. R.

1986-01-01

The clinical value of serum bilirubin subfractionation, using high-performance liquid chromatography (HPLC), was studied in 26 patients with primary biliary cirrhosis (PBC) from whom 59 serum samples were obtained. Total bilirubin (TB) levels were determined by alkaline methanolysis and HPLC

Total bilirubin in nasogastric aspirates: A potential new indicator of ...

African Journals Online (AJOL)

Background: The aim of our study was to investigate if total bilirubin (T-bil), amylase (Amy), and sodium (Na) in nasogastric (NG) aspirates can refl ect gastrointestinal motility reliably. Materials and Methods: NG aspirates from all laparotomies lasting more than 150 min in children less than 12 months old were studied for 3 ...

Exploring the relationship of peripheral total bilirubin, red blood cell, and hemoglobin with blood pressure during childhood and adolescence.

Science.gov (United States)

Chen, Xiao-Tian; Yang, Song; Yang, Ya-Ming; Zhao, Hai-Long; Chen, Yan-Chun; Zhao, Xiang-Hai; Wen, Jin-Bo; Tian, Yuan-Rui; Yan, Wei-Li; Shen, Chong

2017-11-04

Total bilirubin is beneficial for protecting cardiovascular diseases in adults. The authors aimed to investigate the association of total bilirubin, red blood cell, and hemoglobin levels with the prevalence of high blood pressure in children and adolescents. A total of 3776 students (aged from 6 to 16 years old) were examined using cluster sampling. Pre-high blood pressure and high blood pressure were respectively defined as the point of 90th and 95th percentiles based on the Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents. Both systolic and diastolic blood pressure were standardized into z-scores. Peripheral total bilirubin, red blood cell and hemoglobin levels were significantly correlated with age, and also varied with gender. Peripheral total bilirubin was negatively correlated with systolic blood pressure in 6- and 9-year-old boys, whilst positively correlated with diastolic blood pressure in the 12-year-old boys and 13- to 15-year-old girls (p0.05). Total bilirubin could be weakly correlated with both systolic and diastolic blood pressure, as correlations varied with age and gender in children and adolescents; in turn, the increased levels of red blood cell and hemoglobin are proposed to be positively associated with the prevalence of high blood pressure. Copyright © 2017 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Relationship between serum total bilirubin levels and mortality in uremia patients undergoing long-term hemodialysis: A nationwide cohort study.

Science.gov (United States)

Su, Hui-Hsien; Kao, Chia-Man; Lin, Yi-Chun; Lin, Yen-Chung; Kao, Chih-Chin; Chen, Hsi-Hsien; Hsu, Chih-Cheng; Chen, Kuan-Chou; Peng, Chiung-Chi; Wu, Mai-Szu

2017-10-01

Previous studies show that serum bilirubin has potent antioxidant effect and is associated with protection from kidney damage and reduce cardiovascular events. The aim of this study was to examine the association of serum total bilirubin level and mortality in uremia patients who underwent hemodialysis. This is a nationwide retrospective long-term cohort study. Patients were registered in the Taiwan Renal Registry Data System (TWRDS) from 2005 to 2012. A total of 115,535 hemodialysis patients were surveyed and those with valid baseline total bilirubin (TB) data were enrolled. All-cause mortality was the primary outcome. A total of 47,650 hemodialysis patients followed for 27.6 ± 12 months, were divided into 3 groups according to different baseline serum total bilirubin levels (0.1-0.3, 0.3-0.7, 0.7-1.2 mg/dL). Mean age was 61.4 ± 13.6 years, 50% were male, 13% were hepatitis B carriers, and 20% were hepatitis C carriers. Primary outcome was the 3-year mortality. The TB level 0.7-1.2 mg/dL group had high mortality, statistically significant hazard ratio of mortality was 1.14 (crude HR, 95% 1.07-1.20, p bilirubin on hemodialysis patients are needed. Copyright © 2017 Elsevier B.V. All rights reserved.

Ultrastructural changes in the isolated rat kidney induced by conjugated bilirubin and bile acids.

Science.gov (United States)

Gollan, J L; Billing, B H; Huang, S N

1976-10-01

The effects of bilirubin and bile acids on the ultrastructure of proximal renal tubules have been studied using an isolated rat kidney preparation, perfused with a protein-free dextran medium. Control kidneys perfused for 1 h had a normal glomerular filtration rate and effective renal plasma flow; the ultrastructure of proximal tubular cells was well preserved, with normal mitochondria, nuclear and plasma membranes, and microvilli of the brush border. When conjugated bilirubin, prepared from human hepatic bile, was added to the perfusion medium (5-0-7-5 mg/100 ml), marked alterations were observed in some cells, particularly with regard to the mitochondria and plasma membranes. These changes were greatly diminished by the inclusion of bovine albumin in the medium, indicating that the unbound fraction was primarily responsible for the tubular damage. The addition of taurocholate (450 muM), taurochenodeoxycholate (550 muM) or taurolithocholate (250 muM, bound to albumin) also produced plasma membrane changes, but only slight abnormalities were seen in the mitochondria and other structures. These ultrastructural observations support the concept that the elevated plasma levels of conjugated bilirubin and to a lesser extent bile acids are related to the renal failure associated with obstructive jaundice.

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

International Nuclear Information System (INIS)

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

2013-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

Song, Shasha [Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical, University (Daqing), Daqing 163319 (China); Wang, Shuang [Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical, University (Daqing), Daqing 163319 (China); Biopharmaceutical Key Laboratory of Heilongjiang Province, Harbin 150081 (China); Ma, Jun; Yao, Lan; Xing, Hao; Zhang, Lei; Liao, Lin [Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical, University (Daqing), Daqing 163319 (China); Zhu, Daling, E-mail: dalingz@yahoo.com [Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical, University (Daqing), Daqing 163319 (China); Biopharmaceutical Key Laboratory of Heilongjiang Province, Harbin 150081 (China)

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.

Serum bilirubin and antioxidant levels in first degree relatives of patients with ischemic heart disease and normal subjects

International Nuclear Information System (INIS)

Mahmood, N.; Naseem, T.; Mukhtar, F.; Basheer, R.

2011-01-01

Background: Coronary diseases appear to result from an overbalance between radical-generating, compared with radical-scavenging systems, a condition called as oxidative stress. Total antioxidant status (TAS) in human plasma reflects the balance between oxidants and antioxidants in each system. Bilirubin has been considered an antioxidant, with capacity to remove reactive species of oxygen. Present study tried to measure the total antioxidant status of first degree relatives of patients with IHD. Study also tried to evaluate the prognostic role of serum bilirubin in disease prevention or progression. Methods: Seventy five apparently healthy subjects in age group 20-50 years, comprising equal number of males and females, who were first degree relatives of ischemic heart disease patients, were included in the study. Family members were divided on the bases of their numbers, i.e., one family member (Group-A), 2 family members (Group-B) and more than 3 family members (Group-C). Study was cross sectional and carried out in a period of 6 months (Jun 2008-Jan 2009). Subjects with letter of consent were taken from general population. Seventy five healthy age matched people with no history of ischemic heart disease in family were taken as control. An overnight fasting blood sample was taken. Total antioxidant status was determined using a commercially available kit. Serum bilirubin was estimated by auto analyzer. Results: Family history of ischemic heart disease with serum bilirubin showed a significant negative correlation (p<0.05). But the values of TAS failed to show any significant correlation with the family history. It was observed that the value of serum bilirubin was decreased significantly (p<0.05) with an increased number of family members. Total antioxidant status failed to show any significant difference among all the three groups. Conclusion: Our data demonstrated that reduced serum levels of bilirubin were seen in people with a higher prevalence of coronary

No effect modification of serum bilirubin or coffee consumption on the association of gamma-glutamyltransferase with glycated hemoglobin in a cross-sectional study of Japanese men and women

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Wang Zhenjie

2012-10-01

Full Text Available Abstract Background Oxidative stress has been implicated in the development of type 2 diabetes mellitus. Bilirubin is a potent endogenous antioxidant, and coffee is a major source of exogenous antioxidants. Serum gamma-glutamyltransferase (GGT, a marker of oxidative stress, is a strong predictor of the risk of type 2 diabetes mellitus. This study evaluated the effect modification of bilirubin and coffee consumption on the association of serum GGT with glycated hemoglobin (HbA1c and the combined effect of bilirubin and coffee on HbA1c concentrations. Methods The subjects were 4492 men and 6242 women aged 49–76 years who participated in the baseline survey of an on-going cohort study on lifestyle-related diseases in Fukuoka, Japan. Geometric means of HbA1c were examined according to quartile categories of GGT, with stratification by serum total bilirubin (≥ 0.6 mg/dL versus less in men and ≥ 0.5 mg/dL versus less in women and coffee consumption ( Results HbA1 concentrations increased progressively with increasing levels of GGT in both men and women. The increasing trend of HbA1c concentrations associated with GGT did not differ by either bilirubin status or coffee consumption. Both men and women with high bilirubin had consistently lower concentrations of HbA1c across the GGT quartiles. Higher coffee consumption was associated with lower concentrations of HbA1c in women with low bilirubin (trend P = 0.04, but not with high bilirubin (trend P = 0.37. There was no such association between coffee and HbA1c in men with either low or high bilirubin levels. Conclusions Bilirubin is possibly protective against deterioration of glucose metabolism. Further studies are needed regarding the combined effect of bilirubin and coffee on glucose metabolism.

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

Energy Technology Data Exchange (ETDEWEB)

Muhsain, Siti Nur Fadzilah, E-mail: sitinurfadzilah077@ppinang.uitm.edu.my [The University of Queensland, National Research Centre for Environmental Toxicology (Entox), 4072 Brisbane, Queensland (Australia); Faculty of Pharmacy, University Teknologi Mara (Malaysia); Lang, Matti A., E-mail: m.lang@uq.edu.au [The University of Queensland, National Research Centre for Environmental Toxicology (Entox), 4072 Brisbane, Queensland (Australia); Abu-Bakar, A' edah, E-mail: a.abubakar@uq.edu.au [The University of Queensland, National Research Centre for Environmental Toxicology (Entox), 4072 Brisbane, Queensland (Australia)

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

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

International Nuclear Information System (INIS)

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

Transcutaneous bilirubin--comparing the accuracy of BiliChek(R) and JM 103(R) in a regional postnatal unit.

LENUS (Irish Health Repository)

Qualter, Yvonne M

2012-01-31

OBJECTIVE: Transcutaneous bilirubin (TcB) has the potential to reduce serum bilirubin sampling. During a recent survey on the use of TcB in postnatal units in the Republic of Ireland, we identified that only 58% of the 19 units were using TcB and that only two devices were in use, the BiliChek(R) and JM 103(R). We aimed to evaluate and compare these two devices in a regional postnatal unit. METHODS: To evaluate and compare the accuracy of the BiliChek(R) and JM 103(R), we studied simultaneous TcB and total serum bilirubin (TSB) measurements from a population of jaundiced term and near term infants. We evaluated each device with regard to correlation with TSB and potential to safely reduce serum bilirubin testing. RESULTS: Both TcB devices strongly correlated with TSB (r = 0.88 for BiliChek(R) and r = 0.70 for JM 103(R). The BiliChek(R) and JM 103(R) were accurate up to cut-off values of 200 mumol\\/L and 180 mumol\\/L, respectively. Using Bhutani\\'s nomogram, 100% sensitivity was achieved using the 75th percentile for BiliChek(R) and the 40th percentile for JM 103(R). CONCLUSION: Both TcB devices correlated closely with moderately increased TSB levels and are suitable screening tools to identify jaundiced infants that require a serum bilirubin, with upper limit cut-off values. Both devices reduced the need for TSB levels. We found the BiliChek(R) slightly more accurate than the JM 103(R) for our study population. TcB however, is not in widespread use.

Influence of bilirubin on the distribution of 99mTc-HIDA and 99mTc-IODIDA in rats and their interaction with HSA

International Nuclear Information System (INIS)

Jovanovic, M.S.; Zmbova, B.; Zivanov-Stakic, D.; Vladimirov, S.

1993-01-01

The interaction of bilirubin and 99m Tc-HIDA and 99m Tc-IODIDA has been studied in rats. The mechanism of this interaction has been examined at the level of binding with human serum albumin (HSA) by the in vitro method. Percentage of binding with HSA, and affinity constants for 99m Tc-IODIDA were determined with and without bilirubin. Bilirubin was labeled with 99m Tc and its interaction with HSA was also examined. (author) 8 refs.; 2 figs.; 4 tabs

Comparison of the vanadate oxidase method with the diazo method for serum bilirubin determination in dog, monkey, and rat.

Science.gov (United States)

Ameri, Mehrdad; Schnaars, Henry; Sibley, John; Honor, David

2011-01-01

The most widely used method for bilirubin concentration determination is the diazo method, which measures the color of azobilirubin. The vanadate oxidase method is based on oxidation of bilirubin to biliverdin by vanadate. The objective of this study was to compare total and direct bilirubin concentration ([Bt] and [Bd], respectively) determined by the diazo and vanadate oxidase methods in pooled serum samples from dogs, monkeys, and rats spiked with panels of different concentrations of bilirubin standards. Pooled serum samples from 40 dogs, 40 monkeys, and 60 rats were spiked with either ditaurine conjugates of bilirubin or a standard reference material. The results obtained from both assays were compared using Deming regression analysis. The intra- and interassay precision, expressed as a percentage of the coefficient of variation (%CV), was determined for [Bt] and [Bd], and the mean percentage of recovery was calculated. The vanadate oxidase method displayed an excellent correlation (r  =  0.99-1.00) with the diazo method. Using Deming regression, there were minimal negative or positive constant and proportional biases for [Bt] and [Bd]. The precision studies revealed that the vanadate oxidase method has comparable between-run and within-run CVs to those of the diazo method. The recovery study demonstrated that the diazo method more closely approximates the expected values of [Bt]. In conclusion, the vanadate oxidase method is a simple and rapid method that can be employed as an alternative to the diazo method when interfering substances are present in the serum samples of dog, monkey, and rat.

Independent and combined effect of bilirubin and smoking on the progression of chronic kidney disease

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Wang J

2018-01-01

Full Text Available Jiancheng Wang,1,* Binyan Wang,1,2,* Min Liang,1 Guobao Wang,1 Jianping Li,3 Yan Zhang,3 Yong Huo,3 Yimin Cui,4 Xiping Xu,1,5 Xianhui Qin1 1National Clinical Research Center for Kidney Disease, State Key Laboratory for Organ Failure Research, Renal Division, Nanfang Hospital, Southern Medical University, Guangzhou, 2Institute for Biomedicine, Anhui Medical University, Hefei, 3Department of Cardiology, 4Department of Pharmacy, Peking University First Hospital, Beijing, 5Beijing Advanced Innovation Center for Food Nutrition and Human Health, Key Laboratory of Functional Dairy, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China *These authors contributed equally to this work Objective: Whether serum bilirubin and cigarette smoking affect the risk of renal function decline remains inconclusive. We aimed to test the independent and combined effects of bilirubin and cigarette smoking on the progression of chronic kidney disease (CKD in hypertensive adults. Methods: The study population consisted of 12,633 patients in the renal sub-study of the China Stroke Primary Prevention Trial. The primary outcome was progression of CKD, defined as a decrease in estimated glomerular filtration rate (eGFR of ≥30% and to a level of <60 mL/min/1.73 m2 if baseline eGFR was ≥60 mL/min/1.73 m2, or a decrease in eGFR of ≥50% if baseline eGFR was <60 mL/min/1.73 m2, or end-stage renal disease. The secondary outcomes included 1 rapid decline in renal function and 2 annual rate of eGFR decline. Results: The median follow-up duration was 4.4 years. Cigarette smoking had no significant effect on the progression of CKD (odds ratio [OR]: 1.11, 95% confidence interval [95% CI]: 0.78–1.57. However, a significantly lower risk of the primary event (OR: 0.72, 95% CI: 0.55–0.95 was found in participants in tertile 3 compared to those in tertiles 1–2 for total bilirubin (TBiL levels. More importantly, there was an interaction

Intracellular accumulation of bilirubin as a defense mechanism against increased oxidative stress

Czech Academy of Sciences Publication Activity Database

Zelenka, Jaroslav; Muchová, L.; Zelenková, M.; Váňová, K.; Vreman, H.J.; Wong, R.J.; Vítek, L.

2012-01-01

Roč. 94, č. 8 (2012), s. 1821-1827 ISSN 0300-9084 Grant - others:GA MZd(CZ) NT11327 Institutional research plan: CEZ:AV0Z50110509 Keywords : bilirubin * heme oxygenase * hyperbilirubinemia * lipopolysacccharide * oxidative stress Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 3.142, year: 2012

Preparation of chitosan/amino multiwalled carbon nanotubes nanocomposite beads for bilirubin adsorption in hemoperfusion.

Science.gov (United States)

Zong, Wenhui; Chen, Jian; Han, Wenyan; Chen, Jie; Wang, Yue; Wang, Weichao; Cheng, Guanghui; Ou, Lailiang; Yu, Yaoting

2018-01-01

Chitosan-carbon nanotube composite beads combines the advantages of chitosan in forming a stable biocompatible framework and carbon nanotube that provide nanometer effects (high strength and high specific surface area etc.). In this study, chitosan/amino multiwalled carbon nanotubes (CS/AMWCNT) composite beads was prepared by phase-inversion method, in which CS and AMWCNT was crosslinked by ethylene glycol diglycidyl ether (EGDE). The CS/AMWCNT nanocomposite beads produced has been characterized by BET, SEM, TGA, and Raman spectroscopy which exhibited enhanced thermal stability due to the incorporation of AMWCNT. Mechanical test results showed that mechanical strength of the CS/AMWCNT composite beads was significantly enhanced when comparing to unmodified chitosan beads, the breakage percentage decreased from 34.1% to 0.67%. The adsorption capacity for bilirubin was measured in PBS and BSA solutions, and the CS/AMWCNT composite beads with 5 wt% AMWCNT showed much higher adsorption capacity (12.7 mg/g in PBS and 7.6 mg/g in BSA) to bilirubin than chitosan beads (8.5 mg/g in PBS and 4.2 mg/g in BSA). Our nanocomposite beads with excellent hemocompatibility has a high potential application in blood purification as an efficient adsorbent for bilirubin. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 96-103, 2018. © 2016 Wiley Periodicals, Inc.

The albumin-bilirubin grade uncovers the prognostic relationship between hepatic reserve and immune dysfunction in HIV-associated hepatocellular carcinoma.

Science.gov (United States)

Pinato, D J; Sharma, R; Citti, C; Platt, H; Ventura-Cots, M; Allara, E; Chen, T-Y; Dalla Pria, A; Jain, M; Mínguez, B; Kikuchi, L; Kaufman West, E; Merli, M; Kaplan, D E; Hasson, H; Marks, K; Nelson, M; Núñez, M; Aytaman, A; Bower, M; Bräu, N

2018-01-01

Hepatocellular carcinoma (HCC) is a leading cause of liver-related mortality in people living with HIV, where co-infection with hepatotropic viruses accelerates the course of chronic liver disease. To evaluate whether the albumin-bilirubin (ALBI) grade, a more accurate marker of liver dysfunction in HCC, might identify patients with progressive liver dysfunction in the context of HIV/hepatitis co-infection. Using uni- and multi-variable analyses, we studied the albumin-bilirubin grade as a predictor of overall survival (OS) in a large, multi-center cohort of patients with HIV-associated HCC recruited from 44 centres in 9 countries within the Liver Cancer in HIV study group. Patients who underwent liver transplantation were excluded. A total of 387 patients, predominantly HCV co-infected (78%) with balanced representation of all Barcelona Clinic Liver Cancer (BCLC) stages (A = 33%, B = 18%, C = 37%, D = 12%) were recruited. At HCC diagnosis, 84% had been on anti-retrovirals for a median duration of 8.8 years. The albumin-bilirubin grade identified significant differences in median survival of 97 months for grade 1 (95% CI 13-180 months), 17 months for grade 2 (95% CI 11-22 months) and 6 months for grade 3 (95% CI 4-9 months, P bilirubin grade correlated with lower CD4 counts (464/373/288 cells/mm 3 for grades 1/2/3) and higher HIV viraemia (3.337/8.701/61.845 copies/mL for grades 1/2/3, P bilirubin grade highlights the interplay between liver reserve and immune dysfunction as prognostic determinants in HIV-associated HCC. © 2017 John Wiley & Sons Ltd.

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

Science.gov (United States)

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

2016-04-28

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. 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. 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 UGT1A1*28 (TA)7 allele were 4

Dynamic Change of Total Bilirubin after Portal Vein Embolization is Predictive of Major Complications and Posthepatectomy Mortality in Patients with Hilar Cholangiocarcinoma.

Science.gov (United States)

Ou Yang, Qing; Zhang, Sheng; Cheng, Qing-Bao; Li, Bin; Feng, Fei-Ling; Yu, Yong; Luo, Xiang-Ji; Lin, Zhao-Fen; Jiang, Xiao-Qing

2016-05-01

This study aims to evaluate the role of dynamic change in total bilirubin after portal vein embolization (PVE) in predicting major complications and 30-day mortality in patients with hilar cholangiocarcinoma (HCCA). Retrospective analysis of prospectively maintained data of 64 HCCA patients who underwent PVE before hepatectomy in our institution was used. Total bilirubin and other parameters were measured daily in peri-PVE period. The difference between them and the baseline value from days 0-5 to day -1 (∆D1) and days 5-14 to day -1 (∆D2) were calculated. The relationship between ∆D1 and ∆D2 of total bilirubin and major complications as well as 30-day mortality was analyzed. Out of 64 patients, 10 developed major complications (15.6 %) and 6 patients (9.3 %) had died within 30 days after surgery. The ∆D2 of total bilirubin after PVE was most significantly associated with major complications (P 3 (OR = 12.048; 95 % CI 1.019-143.321), ∆D2 of total bilirubin (OR = 1.058; 95 % CI 1.007-1.112), and ∆D2 of prealbumin (OR = 0.975; 95 % CI 0.952-0.999) were associated with higher risk of 30-day mortality after PVE. Receiver operating characteristic curves showed that ∆D2 of total bilirubin were better predictors than ∆D1 for major complications (AUC (∆D2) 0.817; P = 0.002 vs. AUC (∆D1) 0.769; P = 0.007) and 30-day mortality (ACU(∆D2) 0.868; P = 0.003 vs. AUC(∆D1) 0.721;P = 0.076). Patients with increased total bilirubin in 5-14 days after PVE may indicate a higher risk of major complications and 30-day mortality if the major hepatectomy were performed.

Association of human liver bilirubin UDP-glucuronyltransferase activity with a polymorphism in the promoter region of the UGT1A1 gene

NARCIS (Netherlands)

Raijmakers, MTM; Jansen, PLM; Steegers, EAP; Peters, WHM

Background/Aims: Gilbert's syndrome is a benign form of a deficiency in bilirubin glucuronidation. It is associated with a homozygous polymorphism, A(TA)(7)TAA instead of A(TA)(6)TAA, in the TATA-box of the promoter region of the bilirubin UDP-glucuronyltransferase gene. In this study the

Assessment of adjuvant ademetionine therapy for the bilirubin metabolism and target organ function of neonatal jaundice

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Fang Xu

2017-11-01

Full Text Available Objective: To study the effect of adjuvant ademetionine (SAMe therapy on the bilirubin metabolism and target organ function of neonatal jaundice. Methods: A total of 68 children who were diagnosed with neonatal jaundice in Hubei Jianghan Oilfield General Hospital between March 2015 and April 2017 were selected as the research subjects and randomly divided into the SAMe group who received ademetionine combined with blue ray irradiation and the control group who received blue ray irradiation. The serum contents of bilirubin metabolism indexes and target organ injury markers before treatment as well as 3 d and 7 d after treatment. Results: 3 d and 7 d after treatment, serum TBIL, ALT, AST, GGT, TBA, CK-MB, cTnT, MYO, HBDH, NSE, S100B and GFAP levels of both groups were lower than those before treatment, and serum TBIL, ALT, AST, GGT, TBA, CK-MB, cTnT, MYO, HBDH, NSE, S100B and GFAP levels of SAMe group were lower than those of control group. Conclusion: Adjuvant ademetionine therapy can improve the bilirubin metabolism of neonatal jaundice and reduce the central nerve, myocardial and liver injury.

Unilobar versus bilobar biliary drainage: effect on quality of life and bilirubin level reduction

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Shivanand Gamanagatti

2016-01-01

Conclusion: Percutaneous biliary drainage provides good palliation of malignant obstructive jaundice. Partial-liver drainage achieved results as good as those after complete liver drainage with significant improvements in QOL and reduction of the bilirubin level.

Studies on preparing and adsorption property of grafting terpolymer microbeads of PEI-GMA/AM/MBA for bilirubin.

Science.gov (United States)

Gao, Baojiao; Lei, Haibo; Jiang, Liding; Zhu, Yong

2007-06-15

Crosslinking copolymer microbeads with a diameter range of 100-150 microm were synthesized by suspension copolymerization of glycidyl methacrylate (GMA), acrylamide (AM) and N,N'-methylene bisacrylamide (MBA). Subsequently, polyethyleneimine (PEI) was grafted on the surfaces of the terpolymer microbeads GMA/AM/MBA via the ring-opening reaction of the epoxy groups, and the grafting microbeads PEI-GMA/AM/MBA were prepared. In this paper, the adsorption property of the grafting microbeads for bilirubin was mainly investigated, and the effects of various factors, such as pH value, ionic strength and grafting degree of PEI on the surface of grafting microbeads and the adsorption capacity of the grafting microbeads for bilirubin were examined. The batch adsorption experiment results show that by right of the action of grafted polyamine macromolecules PEI, the grafting microbeads PEI-GMA/AM/MBA have quite strong adsorption ability for bilirubin; the isotherm adsorption conforms to Freundlich equation. The pH value of the medium affects the adsorption capacity greatly, As in the nearly neutral solutions with pH 6, the grafting microbeads have the strongest adsorption ability for bilirubin, whereas in acidic and basic solutions their adsorption ability is weak. The ionic strength hardly affects the adsorption ability of the grafting microbeads. The grafting degree of PEI on the surfaces of the grafting microbeads also has a great effect on the adsorption capacity, and higher the grafting degree of PEI on the surface of the microbead PEI-GMA/AM/MBA, the stronger is the adsorption ability of the microbeads.

Prediction of Neonatal Hyperbilirubinemia Using 1st Day Serum Bilirubin Levels.

Science.gov (United States)

Spoorthi, S M; Dandinavar, Siddappa F; Ratageri, Vinod H; Wari, Prakash K

2018-02-15

The study was conducted on Full term neonates with birth weight > 2.5 kg born in KIMS, Hubballi with an objective to determine the first day Total Serum Bilirubin (TSB) value so as to predict subsequent development of significant hyperbilirubinemia in term neonates. All enrolled neonates were sampled for TSB and blood group on Day 1 at 20 ± 4 h and then followed up clinically by Kramer's rule and when the clinical jaundice by Kramer's rule was >10 mg/dl, TSB levels were repeated. A total of 180 newborns were enrolled for the study and 165 babies completed the study. Out of these, 17(10.3%) babies had significant hyperbilirubinemia by day 5 of life. Using Receiver Operating Characteristic (ROC) Curve, a cut off TSB value of 6.15 mg/dl was determined with sensitivity of 82.4%, specificity of 81.8%, positive predictive value of 32.8%, negative predictive value 97.6%. In term neonates, the first day total bilirubin level at 20 ± 4 h of life <6.15 predicts the low risk of subsequent significant hyperbilirubinemia with high probability.

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

Science.gov (United States)

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.

Bioelectrocatalytic mediatorless dioxygen reduction at carbon ceramic electrodes modified with bilirubin oxidase

International Nuclear Information System (INIS)

Nogala, Wojciech; Celebanska, Anna; Szot, Katarzyna; Wittstock, Gunther; Opallo, Marcin

2010-01-01

Carbon ceramic electrodes were prepared by sol-gel processing of a hydrophobic precursor - methyltrimethoxysilane (MTMOS) - together with dispersed graphite microparticles according to a literature procedure. Bilirubin oxidase (BOx) was adsorbed on this electrode from buffer solution and this process was followed by atomic force microscopy (AFM). The electrodes exhibited efficient mediatorless electrocatalytic activity towards dioxygen reduction. The activity depends on the time of adsorption of the enzyme and the pH. The electrode remains active in neutral solution. The bioelectrocatalytic activity is further increased when a fraction of the carbon microparticles is replaced by sulfonated carbon nanoparticles (CNPs). This additive enhances the electrical communication between the enzyme and the electronic conductor. At pH 7 the carbon ceramic electrode modified with bilirubin oxidase retains ca. half of its highest activity. The role of the modified nanoparticles is confirmed by experiments in which a film embedded in a hydrophobic silicate matrix also exhibited efficient mediatorless biocatalytic dioxygen reduction. Scanning electrochemical microscopy (SECM) of the studied electrodes indicated a rather even distribution of the catalytic activity over the electrode surface.

A green and facile approach for synthesizing imine to develop optical biosensor for wide range detection of bilirubin in human biofluids.

Science.gov (United States)

Ellairaja, Sundaram; Shenbagavalli, Kathiravan; Ponmariappan, Sarkaraisamy; Vasantha, Vairathevar Sivasamy

2017-05-15

Bilirubin, a key biomarker for the jaundice and its clinical diagnosis needs a better analytical tool. A novel and simple fluorescent platform based on (2,2'-((1E,1'E)-((6-bromopyridine-2,3-diyl) bis(azanylylidene)) bis(methanylylidene diphenol) (BAMD) was designed. BAMD showed a remarkable fluorescent intensity with a very good quantum yield of 0.85 and lifetime of 870ps. Hence, it was applied for the determination of bilirubin using both colorimetric and fluorimetric techniques in physiological and basic pH. Under optimized experimental conditions, the probe detects bilirubin selectively in the presence of other interfering biomolecules and metal ions. The linear range of detection is 1pM-500µM at pH=7.4 and LOD is 2.8 and 3.3 pM at pH=7.4 and 9.0, respectively, which were reported so far. The probe detects the bilirubin through FRET mechanism. The practical application of the probe was successfully tested in the human blood and urine samples. Based on all above advantages, this simple idea can be applied to design a simple clinical diagnostic tool for jaundice. Copyright © 2016. Published by Elsevier B.V.

A cross-sectional study to evaluate second line virological failure and elevated bilirubin as a surrogate for adherence to atazanavir/ritonavir in two urban HIV clinics in Lilongwe, Malawi.

Science.gov (United States)

Ongubo, Dennis Miyoge; Lim, Robertino; Tweya, Hannock; Stanley, Christopher Chikhosi; Tembo, Petros; Broadhurst, Richard; Gugsa, Salem; Ngongondo, McNeil; Speight, Colin; Heller, Tom; Phiri, Sam; Hosseinipour, Mina C

2017-07-03

Malawi's national antiretroviral therapy program provides atazanavir/ritonavir-based second line regimens which cause concentration-dependent rise in indirect bilirubin. We sought to determine if elevated bilirubin, as a surrogate of atazanavir/ritonavir adherence, can aid in the evaluation of second line virological failure in Malawi. We conducted a cross-sectional study of HIV-infected patients ≥15 years who were on boosted protease inhibitor-based second line antiretroviral therapy for at least 6 months in two urban HIV clinics in Lilongwe, Malawi. Antiretroviral therapy history and adherence data were extracted from the electronic medical records and blood was drawn for viral load, complete blood count, total bilirubin, and CD4 cell count at a clinic visit. Factors associated with virological failure were assessed using multivariate logistic regression model. Out of 376 patients on second line antiretroviral therapy evaluated, 372 (98.9%) were on atazanavir/ritonavir-based therapy and 142 (37.8%) were male. Mean age was 40.9 years (SD ± 10.1), mean duration on second line antiretroviral therapy was 41.9 months (SD ± 27.6) and 256 patients (68.1%) had elevated bilirubin >1.3 mg/dL. Overall, 35 (9.3%) patients had viral load >1000 copies/ml (virological failure). Among the virologically failing vs. non-failing patients, bilirubin was elevated in 34.3% vs. 72.0% respectively (p bilirubin levels (aOR 5.4, p bilirubin levels better predicted virological failure than pill count adherence. Therefore, strategic use of bilirubin and viral load testing to target adherence counseling and support may be cost-effective in monitoring second line antiretroviral therapy adherence and virological failure. Drug resistance testing targeted for patients with virological failure despite elevated bilirubin levels would facilitate timely switch to third line antiretroviral regimens whenever available.

Association of serum bilirubin and promoter variations in HMOX1 and UGT1A1 genes with sporadic colorectal cancer

Czech Academy of Sciences Publication Activity Database

Jirásková, A.; Novotný, J.; Novotný, L.; Vodička, Pavel; Pardini, Barbara; Naccarati, Alessio; Schwertner, H. A.; Hubáček, J. A.; Punčochářová, L.; Šmerhovský, Z.; Vítek, L.

2012-01-01

Roč. 131, č. 7 (2012), s. 1549-1555 ISSN 0020-7136 R&D Projects: GA ČR GA310/07/1430 Grant - others:GA MŠk(CZ) ME849; GA MŠk(CZ) 2B06155; GA MŠk(CZ) LH11030 Program:2B Institutional research plan: CEZ:AV0Z50390703 Keywords : bilirubin * bilirubin UDP-glucuronosyl transferase * colorectal cancer Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 6.198, year: 2012

Bilirubin oxidase bound to multi-walled carbon nanotube-modified gold

International Nuclear Information System (INIS)

Schubert, Kirsten; Goebel, Gero; Lisdat, Fred

2009-01-01

We report on direct electron transfer (DET) reactions of bilirubin oxidase at multi-walled carbon nanotube-(MWCNT) modified gold electrodes. MWCNTs are very suitable for protein immobilisation and provide surface groups that can be used for the stable fixation on electrodes. They can also effectively replace the natural substrate of BOD - bilirubin, the electron donor for oxygen reduction. The bioelectrocatalytic oxygen reduction was recorded using linear sweep voltammetry (LSV) with BOD covalently linked to the nanotubes. The start potential of the bioelectrocatalytic oxygen reduction at pH 7 and a scan rate of 10 mV/s was determined to be 485 ± 10 mV vs. Ag/AgCl, 1 M KCl (720 mV vs. SHE). Current densities up to 500 μA/cm 2 were detected in an air-saturated buffer at room temperature (25 ± 5 deg. C). Experiments with a rotating disk electrode (RDE) indicate a diffusion controlled electrode reaction. A k s value in the range of 80-100 s -1 could be estimated. The DET could also be observed directly by the redox conversion of a copper centre of BOD under anaerobic conditions. A peak pair with a formal potential of 680 ± 10 mV vs. SHE was found. The T1 site is probably addressed by the electrode as indicated by several experimental studies

MODULATION OF THE INFLAMMATORY CYTOKINES AND CYTOPROTECTIVE ENZYME BY BILIRUBIN TREATMENT TO ENHANCE CUTANEOUS WOUND HEALING IN RATS

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Raju Prasad

2017-06-01

Full Text Available Inflammation is the main process of wound healing where expression of certain cytokines likes Interleukin-10 (IL-10 and Tumour necrosis factor ∝ (TNF ∝ plays an important role. In view of the antioxidant potential of bilirubin, the present study was aimed to evaluate time-dependent (day 3, 7, 14 wound healing effects of bilirubin ointment (0.3% in excisional wound model in rats. Thirty-six acclimatized healthy male Wistar rats (120-150g were divided into control and treated groups containing 18 rats each. Each group was further sub- divided into three sub-groups (day 3, 7 and 14 days, n= 6. The ointment base (soft paraffin 90%, lanolin 5% and hard paraffin 5% and bilirubin ointment (0.3% were applied topically once daily for 14 days in control and treated group respectively. The wound area was determined on days 3, 7, and 14. The mRNA expression of TNF ∝ gene and IL-10 gene were determined on days 3, 7 and 14 by Real Time PCR and their protein levels by ELISA method. The protein expression of cyto-protective enzyme HO-1 (Heme oxygenage-1 and growth factor VEGF (Vascular growth factor was determined by western blotting method. The mRNA expression and protein level of TNF ∝ was significantly reduced and IL-10 was significantly increased whereas the expression of HO-1 enzyme and VEGF was significantly increased in treated group on days 3, 7 and 14. It may be concluded that the bilirubin has pro-healing potential.

Indicators of inflammation and cellular damage in chronic asymptomatic or oligosymptomatic alcoholics: correlation with alteration of bilirubin and hepatic and pancreatic enzymes

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Borini Paulo

1999-01-01

Full Text Available Biochemical and hematimetric indicators of inflammation and cell damage were correlated with bilirubin and hepatic and pancreatic enzymes in 30 chronic male alcoholics admitted into psychiatric hospital for detoxification and treatment of alcoholism. Aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase, alkaline phosphatase, and total bilirubin were altered, respectively, in 90%, 63%, 87%, 23% and 23% of the cases. None of the indicators of inflammation (lactic dehydrogenase, altered in 16% of the cases; alpha-1 globulin, 24%; alpha-2 globulin, 88%; leucocyte counts, 28% was correlated with alterations of bilirubin or liver enzymes. Lactic dehydrogenase was poorly sensitive for detection of hepatocytic or muscular damage. Alterations of alpha-globulins seemed to have been due more to alcohol metabolism-induced increase of lipoproteins than to inflammation. Among indicators of cell damage, serum iron, increased in 40% of the cases, seemed to be related to liver damage while creatine phosphokinase, increased in 84% of the cases, related to muscle damage. Hyperamylasemia was found in 20% of the cases and significantly correlated with levels of bilirubin, alkaline phosphatase and gamma-glutamyltransferase. It was indicated that injuries of liver, pancreas, salivary glands, and muscle occurred in asymptomatic or oligosymptomatic chronic alcoholics.

Indicators of inflammation and cellular damage in chronic asymptomatic or oligosymptomatic alcoholics: correlation with alteration of bilirubin and hepatic and pancreatic enzymes

OpenAIRE

Borini, Paulo; Guimarães, Romeu Cardoso

1999-01-01

Biochemical and hematimetric indicators of inflammation and cell damage were correlated with bilirubin and hepatic and pancreatic enzymes in 30 chronic male alcoholics admitted into psychiatric hospital for detoxification and treatment of alcoholism. Aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase, alkaline phosphatase, and total bilirubin were altered, respectively, in 90%, 63%, 87%, 23% and 23% of the cases. None of the indicators of inflammation (lactic dehy...

A Prospective Comparison of Transcutaneous and Serum Bilirubin Within Brief Time Intervals.

Science.gov (United States)

Jones, Denise F; McRea, Abigail R; Knowles, James D; Lin, Feng-Chang; Burnette, Erin; Reller, Lara A; Lohr, Jacob A

2017-10-01

The American Academy of Pediatrics recommends screening newborns ≥35 weeks' gestation with total serum bilirubin (TSB) or transcutaneous bilirubin (TcB) to detect hyperbilirubinemia. Retrospective studies show TcB measurements strongly correlate with TSB; however, few prospective trials document this relationship. Furthermore, Dräger's newest TcB instrument, JM-105, remains unstudied in the United States. We measure TcB on foreheads and sternums of newborns using JM-105 and Bilichek devices within 30 minutes of TSB measurement. We find best overall TcB/TSB correlation with JM-105 on the sternum (mean TcB-TSB difference: -0.21 ± 1.15 mg/dL). Correlations between paired measurements for TcB on the sternum using JM-105 were 0.93 for all TSB levels (n = 178), 0.82 for TSB > 10 (n = 19), 0.69 for TSB > 12 (n = 11), and 0.52 for TSB > 15 (n = 6). TcB accuracy via JM-105 on the sternum significantly differed among races ( P < .001). For 5% of paired measurements, TcB with JM-105 on the sternum underestimated TSB by ≥2 mg/dL, and for <1% by ≥3 mg/dL.

Avaliação laboratorial da estabilidade do padrão calibrador de bilirrubina Laboratorial evaluation of standard bilirubin stability

Directory of Open Access Journals (Sweden)

Maria das Graças da Cunha Leite

2003-01-01

Full Text Available Introdução: O preparo do padrão calibrador de bilirrubina é essencial para um controle adequado das dosagens laboratoriais da bilirrubinemia, visto que estas estão sujeitas a grande variabilidade nos resultados, dependendo do método de dosagem escolhido e da falta de padronização rigorosa na sua execução. Uma vez preparado, este padrão calibrador deve ser dividido em alíquotas e estocado para ser utilizado de rotina. Objetivo: Avaliar os efeitos de diferentes condições de armazenamento de um padrão calibrador de bilirrubina sobre sua estabilidade, com finalidade de calibração de equipamentos utilizados na determinação da bilirrubinemia em neonatos. Material e métodos: Após o preparo de um padrão calibrador com 25mg/dl de bilirrubina, este foi armazenado a 4°C, congelado a - 20°C e a - 70°C. Durante nove meses foram feitas dosagens consecutivas da bilirrubina da solução padrão, as quais foram analisadas através da análise de variância de duas vias com blocagem. Resultados: As amostras congeladas a - 70°C não sofreram degradação significativa nos nove meses estudados, enquanto que, no período de três meses, as congeladas a - 20°C e a 4°C sofreram uma degradação de 5% e 24,18%, respectivamente, dos níveis iniciais de bilirrubina. Conclusão: A estocagem do padrão calibrador de bilirrubina a - 70°C é a recomendada para a preservação dos níveis de bilirrubina.Background: The preparation of a standard bilirubin is essential for an adequate quality control of laboratorial bilirubinemia measurements because they are subjected to a large variability in results depending on the dosage method used and the lack of a rigorous standardization of its performance. Once prepared, this standard solution has to be divided in aliquots and stored to be routinely used. Objective: To evaluate the effect of different conditions of the standard solution storage in the stability of bilirubin with the purpose of using it for

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

International Nuclear Information System (INIS)

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

The crystal structure of bilirubin oxidase (BOD) from M. verrucaria has been determined at 2.3 Å resolution using a merohedrally twinned crystal. BOD has four copper-coordination sites that are almost identical to those of other multicopper oxidases and is also very similar to them in overall structure. 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 P6 3 . 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

Identification of heme oxygenase-1 stimulators by a convenient ELISA-based bilirubin quantification assay.

Science.gov (United States)

Rücker, Hannelore; Amslinger, Sabine

2015-01-01

The upregulation of heme oxygenase-1 (HO-1) has proven to be a useful tool for fighting inflammation. In order to identify new HO-1 inducers, an efficient screening method was developed which can provide new lead structures for drug research. We designed a simple ELISA-based HO-1 enzyme activity assay, which allows for the screening of 12 compounds in parallel in the setting of a 96-well plate. The well-established murine macrophage cell line RAW264.7 is used and only about 26µg of protein from whole cell lysates is needed for the analysis of HO-1 activity. The quantification of HO-1 activity is based on an indirect ELISA using the specific anti-bilirubin antibody 24G7 to quantify directly bilirubin in the whole cell lysate, applying a horseradish peroxidase-tagged antibody together with ortho-phenylenediamine and H2O2 for detection. The bilirubin is produced on the action of HO enzymes by converting their substrate heme to biliverdin and additional recombinant biliverdin reductase together with NADPH at pH 7.4 in buffer. This sensitive assay allows for the detection of 0.57-82pmol bilirubin per sample in whole cell lysates. Twenty-three small molecules, mainly natural products with an α,β-unsaturated carbonyl unit such as polyphenols, including flavonoids and chalcones, terpenes, an isothiocyanate, and the drug oltipraz were tested at typically 6 or 24h incubation with RAW264.7 cells. The activity of known HO-1 inducers was confirmed, while the chalcones cardamonin, flavokawain A, calythropsin, 2',3,4'-trihydroxy-4-methoxychalcone (THMC), and 2',4'-dihydroxy-3,4-dimethoxychalcone (DHDMC) were identified as new potent HO-1 inducers. The highest inductive power after 6h incubation was found at 10µM for DHDMC (6.1-fold), carnosol (3.9-fold), butein (3.1-fold), THMC (2.9-fold), and zerumbone (2.5-fold). Moreover, the time dependence of HO-1 protein production for DHDMC was compared to its enzyme activity, which was further evaluated in the presence of

Deracemization of bilirubin as the marker of the chirality of micellar aggregates.

Science.gov (United States)

Sorrenti, Alessandro; Altieri, Barbara; Ceccacci, Francesca; Di Profio, Pietro; Germani, Raimondo; Giansanti, Luisa; Savelli, Gianfranco; Mancini, Giovanna

2012-01-01

The deracemization of bilirubin in micellar aggregates of structurally correlated chiral surfactants was studied by circular dichroism experiments and exploited as the marker of the expression of chirality of the aggregates. The obtained results suggest that the hydrophobic interactions control the transfer of chirality from the monomers to the aggregates, and that different regions of the same aggregate might feature opposite enantiorecognition capabilities. Copyright © 2011 Wiley-Liss, Inc.

Identification of a liver growth factor as an albumin-bilirubin complex.

OpenAIRE

Díaz-Gil, J J; Gavilanes, J G; Sánchez, G; García-Cañero, R; García-Segura, J M; Santamaría, L; Trilla, C; Escartín, P

1987-01-01

We have reported the purification and characterization of a protein that behaves as a liver growth factor, showing activity either in vivo or in vitro [Díaz-Gil et al. (1986) Biochem. J. 235, 49-55]. In the present paper, we identify this liver growth factor (LGF) as an albumin-bilirubin complex. This conclusion is supported by the results of chemical and spectroscopic characterization of this protein as well as by experiments in vivo. Incubation of albumin isolated from normal rats with bili...

Adjusting CA19-9 values to predict malignancy in obstructive jaundice: Influence of bilirubin and C-reactive protein

Science.gov (United States)

La Greca, Gaetano; Sofia, Maria; Lombardo, Rosario; Latteri, Saverio; Ricotta, Agostino; Puleo, Stefano; Russello, Domenico

2012-01-01

AIM: To find a possible relationship between inflammation and CA19-9 tumor marker by analyzing data from patients with benign jaundice (BJ) and malignant jaundice (MJ). METHODS: All patients admitted for obstructive jaundice, in the period 2005-2009, were prospectively enrolled in the study, obtaining a total of 102 patients. On admission, all patients underwent complete standard blood test examinations including C-reactive protein (CRP), bilirubin, CA19-9. Patients were considered eligible for the study when they presented obstructive jaundice confirmed by instrumental examinations and increased serum bilirubin levels (total bilirubin > 2.0 mg/dL). The standard cut-off level for CA19-9 was 32 U/mL, whereas for CRP this was 1.5 mg/L. The CA19-9 level was adjusted by dividing it by the value of serum bilirubin or by the CRP value. The patients were divided into 2 groups, MJ and BJ, and after the adjustment a comparison between the 2 groups of patients was performed. Sensitivity, specificity and positive predictive values were calculated before and after the adjustment. RESULTS: Of the 102 patients, 51 were affected by BJ and 51 by MJ. Pathologic CA19-9 levels were found in 71.7% of the patients. In the group of 51 BJ patients there were 29 (56.9%) males and 22 (43.1%) females with a median age of 66 years (range 24-96 years), whereas in the MJ group there were 24 (47%) males and 27 (53%) females, with a mean age of 70 years (range 30-92 years). Pathologic CA19-9 serum level was found in 82.3% of MJ. CRP levels were pathologic in 66.6% of the patients with BJ and in 49% with MJ. Bilirubin and CA19-9 average levels were significantly higher in MJ compared with BJ (P = 0.000 and P = 0.02), while the CRP level was significantly higher in BJ (P = 0.000). Considering a CA19-9 cut-off level of 32 U/mL, 82.3% in the MJ group and 54.9% in the BJ group were positive for CA19-9 (P = 0.002). A CA19-9 cut-off of 100 U/mL increases the difference between the two groups: 35.3% in

The effect of the pre-pregnancy weight of the mother and the gestational weight gain on the bilirubin level of term newborn.

Science.gov (United States)

Özdek, Suat; Kul, Mustafa; Barış Akcan, Abdullah; Çekmez, Ferhat; Aydemir, Gökhan; Aydınöz, Seçil; Karademir, Ferhan; Süleymanoğlu, Selami

2016-01-01

Jaundice is a problem in newborns. There are many maternal and infant-related factors affecting neonatal jaundice. The maternal pre-pregnancy weight, maternal body mass index (BMI) and gestational weight gain may have an effect on the newborn bilirubin levels. We research the effect of the maternal pre-pregnancy weight and gestational weight gain on the bilirubin levels of the newborn infants in the first 2 weeks prospectively. Term and healthy infants who were born between 38 and 42 weeks in our clinic were included in the study. Maternal pre-pregnancy BMIs were calculated. Babies were divided into three groups according to their mothers' advised amount of gestational weight gain. Total serum bilirubin (TSB) values of the newborns were measured in the 2nd, 5th and 15th postnatal days. In our study, the 5th and 15th day capillary bilirubin level of the babies with mothers who gained more weight than the advised amount during pregnancy were found statistically significant higher compared to the other two groups (p mothers who gained more weight than the advised amount were found statistically significant higher compared to the other two groups (p mothers who gained more weight than the advised amount were under risk for newborn jaundice. Therefore, these babies should be monitored more closely for neonatal jaundice and prolonged jaundice.

Interaction of bilirubin with Ag and Au ions: green synthesis of bilirubin-stabilized nanoparticles

Energy Technology Data Exchange (ETDEWEB)

Shukla, Shashi P. [Bhabha Atomic Research Centre, Radiation and Photochemistry Division (India); Roy, Mainak [Bhabha Atomic Research Centre, Chemistry Division (India); Mukherjee, Poulomi [Bhabha Atomic Research Centre, Nuclear Agriculture and Biotechnology Division (India); Tyagi, A. K. [Bhabha Atomic Research Centre, Chemistry Division (India); Mukherjee, Tulsi [Bhabha Atomic Research Centre, Chemistry Group (India); Adhikari, Soumyakanti, E-mail: asoumya@barc.gov.in [Bhabha Atomic Research Centre, Radiation and Photochemistry Division (India)

2012-07-15

We report a simple green chemistry to synthesize and stabilize monodispersed silver and gold nanoparticles sols by reducing aqueous solution of the respective metal salts in the presence of bilirubin (BR). No additional capping agent was used in the process of stabilization of the nanoparticles. As a completely new finding, we have observed that BR known to be toxic at higher concentration in one hand and conversely an antioxidant at physiological concentration reduces these metal ions to form the respective metal nanoparticles. Moreover, BR and its oxidized products also serve as capping agents to the nanoparticles. The particles were characterized by transmission electron microscopy. BR and its oxidized products capped nanoparticles are stable for months. The UV-Vis absorption spectra of the silver sol show the plasmon peak of symmetric spherical particles which was further reflected in the TEM images. The sizes of the silver particles were about 5 nm. These silver particles showed reasonably high antibacterial activity in Gram negative wild type E. coli. In the case of interaction of BR with gold ions, we could obtain cubic gold nanoparticles of average sizes 20-25 nm. Possible modes of anchorage of BR and/its oxidized products to silver nanoparticles were demonstrated by surface-enhanced resonance Raman spectroscopy (SERS) that in turn demonstrated the feasibility of using these nanoparticles as SERS substrates.

Interaction of bilirubin with Ag and Au ions: green synthesis of bilirubin-stabilized nanoparticles

Science.gov (United States)

Shukla, Shashi P.; Roy, Mainak; Mukherjee, Poulomi; Tyagi, A. K.; Mukherjee, Tulsi; Adhikari, Soumyakanti

2012-07-01

We report a simple green chemistry to synthesize and stabilize monodispersed silver and gold nanoparticles sols by reducing aqueous solution of the respective metal salts in the presence of bilirubin (BR). No additional capping agent was used in the process of stabilization of the nanoparticles. As a completely new finding, we have observed that BR known to be toxic at higher concentration in one hand and conversely an antioxidant at physiological concentration reduces these metal ions to form the respective metal nanoparticles. Moreover, BR and its oxidized products also serve as capping agents to the nanoparticles. The particles were characterized by transmission electron microscopy. BR and its oxidized products capped nanoparticles are stable for months. The UV-Vis absorption spectra of the silver sol show the plasmon peak of symmetric spherical particles which was further reflected in the TEM images. The sizes of the silver particles were about 5 nm. These silver particles showed reasonably high antibacterial activity in Gram negative wild type E. coli. In the case of interaction of BR with gold ions, we could obtain cubic gold nanoparticles of average sizes 20-25 nm. Possible modes of anchorage of BR and/its oxidized products to silver nanoparticles were demonstrated by surface-enhanced resonance Raman spectroscopy (SERS) that in turn demonstrated the feasibility of using these nanoparticles as SERS substrates.

Influence of skin optical losses on configurational photoisomerization of bilirubin during phototherapy

International Nuclear Information System (INIS)

Pratesi, R.; Cecchi, G.

1984-01-01

Kubelka-Munk theory of radiation transfer in turbid media is applied to determine the influence of skin optical losses on the efficiency of phototherapy of neonatal hyperbilirubinemia. By using a multilayer model of the skin and a rate equation analysis of bilirubin photoisomerization, the photon absorption rates of birilubin and of its configurational photoisomers and, in turn, the photoequilibrium concentrations and rise time are calculated for spectrally Gaussian light sources and fluorescent lamps used in phototherapy

Identification of bilirubin reduction products formed by Clostridium perfringens isolated from human neonatal fecal flora

Czech Academy of Sciences Publication Activity Database

Vítek, L.; Majer, F.; Muchová, L.; Zelenka, J.; Jirásková, A.; Branny, Pavel; Malina, J.; Ubik, Karel

2006-01-01

Roč. 833, - (2006), s. 149-157 ISSN 1570-0232 R&D Projects: GA ČR GA310/02/1436 Institutional research plan: CEZ:AV0Z50200510; CEZ:AV0Z40550506 Keywords : bilirubin * bacteria l reduction * intestinal microflora Subject RIV: EE - Microbiology, Virology Impact factor: 2.647, year: 2006

Anti-cancer effects of blue-green alga Spirulina platensis, a natural source of bilirubin-like tetrapyrrolic compounds

Czech Academy of Sciences Publication Activity Database

Koníčková, R.; Vaňková, K.; Vaníková, J.; Váňová, K.; Muchová, L.; Subhanová, I.; Zadinová, M.; Zelenka, Jaroslav; Dvořák, Aleš; Kolář, Michal; Strnad, Hynek; Rimpelová, S.; Ruml, T.; Wong, R.J.; Vítek, L.

2014-01-01

Roč. 13, č. 2 (2014), s. 273-283 ISSN 1665-2681 Institutional support: RVO:67985823 ; RVO:68378050 Keywords : bilirubin * chlorophyll * heme oxygenase * phycocyanin * phycocyanobilin * Spirulina platensis * tetrapyrroles Subject RIV: FD - Oncology ; Hematology Impact factor: 2.065, year: 2014

Acute effect of weight loss on levels of total bilirubin in obese, cardiovascular high-risk patients: an analysis from the lead-in period of the Sibutramine Cardiovascular Outcome trial

DEFF Research Database (Denmark)

Andersson, Charlotte; Weeke, Peter; Fosbøl, Emil Loldrup

2009-01-01

Low levels of bilirubin are associated with an increased risk of cardiovascular adverse events. Weight reduction is known to reduce several cardiovascular risk factors, but effects on bilirubin levels have not been reported. We studied the response of weight loss therapy with sibutramine and life......Low levels of bilirubin are associated with an increased risk of cardiovascular adverse events. Weight reduction is known to reduce several cardiovascular risk factors, but effects on bilirubin levels have not been reported. We studied the response of weight loss therapy with sibutramine...... and lifestyle change on levels of total bilirubin in an overweight or obese, cardiovascular high-risk population. Data from the first 4 weeks of the lead-in period of the Sibutramine Cardiovascular Outcome study were analyzed. A total of 10 198 patients provided body weight measurements before and after 4 weeks...... of sibutramine treatment (10 mg daily), of whom 1059 (10.4%) gained weight, 1467 (13.7%) lost greater than 0% to 1%, 2492 (23.2%) lost greater than 1% to 2%, 2280 (21.2%) lost greater than 2% to 3%, 1498 (13.9%) lost greater than 3% to 4%, and 1402 (13.1%) lost greater than 4% of their initial weight...

Phenobarbital and Phototherapy Combination Enhances Decline of Total Serum Bilirubin and May Decrease the Need for Blood Exchange Transfusion in Newborns with Isoimmune Hemolytic Disease

Science.gov (United States)

Kaabneh, Mahmoud AF; Salama, Ghassan SA; Shakkoury, Ayoub GA; Al-abdallah, Ibrahim MH; Alshamari, Afrah; Halaseh, Ruba AA

2015-01-01

OBJECTIVE The objective of this study was to evaluate the effect of phenobarbital and phototherapy combination on the total serum bilirubin of the newborn infants with isoimmune hemolytic disease (IHD) and its impact on blood exchange transfusion rates. PATIENTS AND METHOD This single-blinded, prospective, randomized, controlled trial was conducted between March 2013 and December 2014 at the pediatric ward of two Military Hospitals in Jordan. A total of 200 full-term neonates with IHD were divided randomly into two groups: (1) the phenobarbital plus phototherapy group (n = 103), and (2) the phototherapy-only group (n = 97). Infants in group 1 received an oral dose of 2.5 mg/kg phenobarbital every 12 hours for 3 days in addition to phototherapy. The total serum bilirubin was observed. RESULTS Of the total 200 included newborn infants, 186 infants completed the study: 97 infants were included in group 1 and 89 infants in group 2. The difference between the mean total serum bilirubin levels at 24, 48, and 72 hours after starting the trial was clinically and statistically significant at P newborn infants with IHD, as it results in a faster decline in total serum bilirubin, thus decreasing the need for blood exchange transfusion than phototherapy alone. PMID:26309423

Increased conjugated bilirubin is sufficient to initiate screening for biliary atresia

DEFF Research Database (Denmark)

Madsen, Stine Skipper; Kvist, Nina; Thorup, Jørgen

2015-01-01

. This percentage value has caused diagnostic trouble over the years. The objective of the present study was to investigate the possibility of changing the recommendations. METHODS: This was a retrospective analysis of the medical records of children operated for biliary atresia in the 1993-2012 period. RESULTS......: mean 129.7 μmol/l (42-334 μmol/l) and 73% (28-97%), respectively. CONCLUSION: The total amount of conjugated bilirubin above 20 μmol/l is sufficient to require further evaluation for biliary atresia. The percentage value is unnecessary and may cause confusion. FUNDING: none. TRIAL REGISTRATION...

Bilirubin concentration is positively associated with haemoglobin concentration and inversely associated with albumin to creatinine ratio among Indigenous Australians: eGFR Study.

Science.gov (United States)

Hughes, J T; Barzi, F; Hoy, W E; Jones, G R D; Rathnayake, G; Majoni, S W; Thomas, M A B; Sinha, A; Cass, A; MacIsaac, R J; O'Dea, K; Maple-Brown, L J

2017-12-01

Low serum bilirubin concentrations are reported to be strongly associated with cardio-metabolic disease, but this relationship has not been reported among Indigenous Australian people who are known to be at high risk for diabetes and chronic kidney disease (CKD). serum bilirubin will be negatively associated with markers of chronic disease, including CKD and anaemia among Indigenous Australians. A cross-sectional analysis of 594 adult Aboriginal and Torres Strait Islander (TSI) people in good health or with diabetes and markers of CKD. Measures included urine albumin: creatinine ratio (ACR), estimated glomerular filtration rate (eGFR), haemoglobin (Hb) and glycated haemoglobin (HbA1c). Diabetes was defined by medical history, medications or HbA1c≥6.5% or ≥48mmol/mol. Anaemia was defined as Hbbilirubin was performed. Participants mean (SD) age was 45.1 (14.5) years, and included 62.5% females, 71.7% Aboriginal, 41.1% with diabetes, 16.7% with anaemia, 41% with ACR>3mg/mmol and 18.2% with eGFRbilirubin concentration was lower in females than males (6 v 8μmol/L, pbilirubin; Hb and cholesterol (both positively related) and ACR, triglycerides, Aboriginal ethnicity and female gender (all inversely related). Serum bilirubin concentrations were positively associated with Hb and total cholesterol, and inversely associated with ACR. Further research to determine reasons explaining lower bilirubin concentrations among Aboriginal compared with TSI participants are needed. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

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

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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. Copyright © 2016 Elsevier Inc. All rights reserved.

Bilirubin Oxidase from Myrothecium verrucaria Physically Absorbed on Graphite Electrodes. Insights into the Alternative Resting Form and the Sources of Activity Loss.

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Federico Tasca

Full Text Available 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.

Photo-isomerization and oxidation of bilirubin in mammals is dependent on albumin binding.

Science.gov (United States)

Goncharova, Iryna; Jašprová, Jana; Vítek, Libor; Urbanová, Marie

2015-12-01

The bilirubin (BR) photo-conversion in the human body is a protein-dependent process; an effective photo-isomerization of the potentially neurotoxic Z,Z-BR as well as its oxidation to biliverdin in the antioxidant redox cycle is possible only when BR is bound on serum albumin. We present a novel analytical concept in the study of linear tetrapyrroles metabolic processes based on an in-depth mapping of binding sites in the structure of human serum albumin (HSA). A combination of fluorescence spectroscopy, circular dichroism (CD) spectroscopy, and molecular modeling methods was used for recognition of the binding site for BR, its derivatives (mesobilirubin and bilirubin ditaurate), and the products of the photo-isomerization and oxidation (lumirubin, biliverdin, and xanthobilirubic acid) on HSA. The CD spectra and fluorescent quenching of the Trp-HSA were used to calculate the binding constants. The results of the CD displacement experiments performed with hemin were interpreted together with the findings of molecular docking performed on the pigment-HSA complexes. We estimated that Z,Z-BR and its metabolic products bind on two independent binding sites. Our findings support the existence of a reversible antioxidant redox cycle for BR and explain an additional pathway of the photo-isomerization process (increase of HSA binding capacity; the excess free [unbound] BR can be converted and also bound to HSA). Copyright © 2015 Elsevier Inc. All rights reserved.

Inverse association between serum bilirubin levels and arterial stiffness in Korean women with type 2 diabetes.

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Eun Sook Kim

Full Text Available BACKGROUND: Considerable evidence suggests that bilirubin is a potent physiologic antioxidant that may provide important protection against cardiovascular disease (CVD and inflammation. We investigated the relationship between serum total bilirubin (TB levels and arterial stiffness, measured by the brachial-ankle pulse wave velocity (baPWV, in patients with type 2 diabetes. METHODS: We conducted a cross-sectional analysis of 1,711 subjects with type 2 diabetes (807 men and 904 women; mean age, 57.1 years. The subjects were stratified based on gender-specific tertiles of TB values, and a high baPWV was defined as greater than 1,745 cm/s ( >75th percentile. RESULTS: The serum TB concentration was negatively correlated with the duration of diabetes, HbA1c, the 10-year Framingham risk score, and baPWV and was positively correlated with high-density lipoprotein cholesterol and the eGFR in both genders. Inverse association between TB categories and unadjusted prevalence of high PWV was only observed in women. After adjusting for confounding factors, the TB levels were inversely associated with a greater risk of a high baPWV, both as a continuous variable [a 1-SD difference; odds ratio (OR, 0.70; 95% confidence interval (CI, 0.54-0.90; P = 0.005] and when categorized in tertiles (the highest vs. the lowest tertile; OR, 0.49; 95% CI, 0.28-0.85; P = 0.011 in women but not in men. The relationship remained significant even after adjusting for retinopathy and nephropathy. CONCLUSIONS: Low TB levels were significantly associated with arterial stiffness in Korean women with type 2 diabetes. Our data suggested that bilirubin may protect against macrovascular disease in diabetic women.

ABO hemolytic disease of the fetus and newborn: thirteen years of data after implementing a universal bilirubin screening and management program.

Science.gov (United States)

Christensen, R D; Baer, V L; MacQueen, B C; O'Brien, E A; Ilstrup, S J

2018-02-06

ABO hemolytic disease occurs among neonates with blood groups A or B delivered to group O women. Extreme neonatal hyperbilirubinemia due to ABO disease has been reported, but its frequency is not well known. We sought to determine the odds of developing severe ABO hemolytic disease in the 13 years since adopting universal bilirubin screening/management in the Intermountain Healthcare system. We conducted a retrospective analysis of neonates born between 2004 and 2016, defining "severe hemolytic disease" as; (1) total serum bilirubin (TSB) >25 mg/dL, or (2) hospital readmission for jaundice, or (3) bilirubin encephalopathy. Neonates born to group O (+) mothers were included and considered either; (1) Controls (not at risk for ABO disease because they were group O), (2) Study subjects (at risk for ABO disease because they were group A or B). Of 400,531 live births, 47% were to group O women; 86% of whom were group O (+). Overall, 42,529 (27%) neonates born to group O (+) women had their blood group determined; 29,729 (68%) were O, 10,682 (25%) A, and 3109 (7%) B. Peak TSBs during the first 10 days were higher in group A (11.0 ± 4.2 mg/dL) and B (11.5 ± 4.3) than group O neonates (10.3 ± 4.1). However the relative risks of a TSB ≥25 mg/dL, readmission for jaundice, or kernicterus, were the same in the control vs. study groups. In our health system, severe hemolytic disease in neonates born to group O (+) woman is not more likely in group A or B neonates than in controls (group O). We recognize that in other practices, particularly those who do not have a universal bilirubin screening/management program, ABO hemolytic disease severity might be different than in our system.

Veno-Occlusive Disease of the Liver in the Absence of Elevation in Bilirubin in Pediatric Patients after Hematopoietic Stem Cell Transplantation

Science.gov (United States)

Myers, Kasiani C.; Dandoy, Christopher; El-Bietar, Javier; Davies, Stella M.; Jodele, Sonata

2016-01-01

Veno-occlusive disease (VOD) of the liver is a well-described and significant complication of hematopoietic stem cell transplantation (HSCT), with limited successful therapeutic options in severe cases. Prompt diagnosis and initiation of treatment is crucial to restrict the extent of disease. However, a subset of patients may not meet all current diagnostic criteria at presentation, and waiting for these to be met may delay therapy. We retrospectively reviewed 794 HSCT patients treated at our institution between 2003 and 2013, identifying 17 (2.1%) who developed VOD. Of these, 5 (29%) were noted to have an absence of elevated bilirubin at the time of VOD diagnosis and reversal of portal venous flow on ultrasound. Median total and conjugated bilirubin at VOD diagnosis were 1.0 and 0.2 mg/dL, respectively. All 5 patients were subsequently diagnosed with multiorgan failure associated with VOD, including 1 with encephalopathy. Four were treated with intravenous high-dose methylprednisolone (500 mg/m2 per dose every 12 hours for 6 doses). One patient received defibrotide therapy in addition to steroids and another supportive care alone. VOD resolved in 4 of 5 patients, with median time to resolution of VOD, defined as recovery of all organ function and normalization of bilirubin and portal venous flow, of 8 days. Two patients died later from progressive primary disease and chronic graft-versus-host disease, respectively. We conclude that a high index of suspicion for VOD should be maintained in patients despite lack of bilirubin elevation in the presence of other diagnostic criteria such as hepatomegaly, abdominal pain, ascites, or weight gain. Early ultrasound evaluation in these patients may lead to more timely diagnosis and therapeutic interventions. PMID:25300869

Evaluation of Treatment Thresholds for Unconjugated Hyperbilirubinemia in Preterm Infants : Effects on Serum Bilirubin and on Hearing Loss?

NARCIS (Netherlands)

Hulzebos, Christian V.; van Dommelen, Paula; Verkerk, Paul H.; Dijk, Peter H.; Van Straaten, Henrica L. M.

2013-01-01

Background: Severe unconjugated hyperbilirubinemia may cause deafness. In the Netherlands, 25% lower total serum bilirubin (TSB) treatment thresholds were recently implemented for preterm infants. Objective: To determine the rate of hearing loss in jaundiced preterms treated at high or at low TSB

Evaluation of Treatment Thresholds for Unconjugated Hyperbilirubinemia in Preterm Infants: Effects on Serum Bilirubin and on Hearing Loss?

NARCIS (Netherlands)

Hulzebos, C.V.; Dommelen, P. van; Verkerk, P.H.; Dijk, P.H.; Straaten, H.L.M. van

2013-01-01

Background:Severe unconjugated hyperbilirubinemia may cause deafness. In the Netherlands, 25% lower total serum bilirubin (TSB) treatment thresholds were recently implemented for preterm infants.Objective:To determine the rate of hearing loss in jaundiced preterms treated at high or at low TSB

The study on clinical value of the detection about serum and Unconjugated Bilirubin in diagnosis of neonatal jaundice.

Science.gov (United States)

Wang, Guangzhou; Wang, Jiefei; Huang, Nannan; Yu, Fengqin

2016-01-01

In this paper, the clinical value of the detection about serum and unconjugated bilirubin (UCB) in neonatal jaundice was studied to found an effective and rapid method for diagnose of neonatal jaundice. ALB (Serum Albumin), total serum bilirubin (TSB) and UCB were detected by ELISA method among the 100 cases with neonatal jaundice selected for the study. The values of ALB, UCB and TSB in moderate jaundice patients were (42.83±3.87) g/L, (287.35±44.38) μm/L, (304.16±43.40) μm/L, respectively; as for the severe jaundice patients, the values were (38.41±4.82) g/L, (354.38±48.75) μm/L, (375.20±47.51) μm/L. The results showed significant differences with the pjaundice patients. The level of ALB, UCB, TSB in hemolytic jaundice, obstructive jaundice and jaundice caused by other infections also had significant differences, and the difference was statistically significant (pjaundice.

High sensitive C-reactive protein and serum amyloid A are inversely related to serum bilirubin : effect-modification by metabolic syndrome

NARCIS (Netherlands)

Deetman, Petronella E.; Bakker, Stephan J. L.; Dullaart, Robin P. F.

2013-01-01

Background: Bilirubin has been implicated in cardiovascular protection by virtue of its anti-inflammatory and anti-oxidative properties. The metabolic syndrome is featured by enhanced low-grade systemic inflammation and oxidative stress. Serum amyloid A (SAA) impairs anti-oxidative properties of

Clinical value and diagnostic relevance of 99mTc-diethyl-IODO-IDA (IODIDA) compared to 99mTc-diethyl-IDA (HEPATOBIDA) in patients with increased serum bilirubin

International Nuclear Information System (INIS)

Spitz, J.; Hildebrandt, H.; Clemenz, N.; Schattenberg, J.; Weigand, H.

1987-01-01

In a combined study 20 patients with diseases of liver parenchyma and/or of the bile duct system were investigated with SOLCO-SCINT-IODIDA and SOLCOSCINT-HEPATOBIDA. Patients with normal serum bilirubin do not show qualitative or quantitative differences in hepatobiliary function parameters. With increasing serum bilirubin (X = 15,4 ng/ml, range 3,9 to 42,6 ng/ml) a markedly increased diagnostic relevance could be shown up for IODIDA. Image contrast between liver and heart is better for IODIDA by a factor 2, and there was never seen any renal activity excretion in IODIDA-studies up to serum bilirubin of 40 mg/dl. In 2/3 of the studies IODIDA provided better clinical results, whereas in 1/3 of the cases both compounds did not show significant differences. In no case HIDA showed better results compared to IODIDA. IODIDA proves to be the radiopharmaceutical of choice for all hepatobiliary function studies. (orig.) [de

Spontaneous evolution in bilirubin levels predicts liver-related mortality in patients with alcoholic hepatitis.

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Minjong Lee

Full Text Available The accurate prognostic stratification of alcoholic hepatitis (AH is essential for individualized therapeutic decisions. The aim of this study was to develop a new prognostic model to predict liver-related mortality in Asian AH patients. We conducted a hospital-based, retrospective cohort study using 308 patients with AH between 1999 and 2011 (a derivation cohort and 106 patients with AH between 2005 and 2012 (a validation cohort. The Cox proportional hazards model was constructed to select significant predictors of liver-related death from the derivation cohort. A new prognostic model was internally validated using a bootstrap sampling method. The discriminative performance of this new model was compared with those of other prognostic models using a concordance index in the validation cohort. Bilirubin, prothrombin time, creatinine, potassium at admission, and a spontaneous change in bilirubin levels from day 0 to day 7 (SCBL were incorporated into a model for AH to grade the severity in an Asian patient cohort (MAGIC. For risk stratification, four risk groups were identified with cutoff scores of 29, 37, and 46 based on the different survival probabilities (P<0.001. In addition, MAGIC showed better discriminative performance for liver-related mortality than any other scoring system in the validation cohort. MAGIC can accurately predict liver-related mortality in Asian patients hospitalized for AH. Therefore, SCBL may help us decide whether patients with AH urgently require corticosteroid treatment.

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

Science.gov (United States)

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 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 level and hyperbilirubinemia risk in elderly subjects. UGT1A1 intronic single-nucleotide polymorphisms (SNPs) (rs6742078, rs887829, rs4148324) serve as proxy markers for the low-frequency and rare UGT1A1 variants, thereby providing mechanistic explanation to the relationship between UGT1A1 intronic SNPs and the UGT1A1 enzyme activity. UGT1A1 and UGT1A6 variants might be potentially associated with gallstone-related cholecystectomy risk. PMID:26039129

Phenobarbital and Phototherapy Combination Enhances Decline of Total Serum Bilirubin and May Decrease the Need for Blood Exchange Transfusion in Newborns with Isoimmune Hemolytic Disease

Directory of Open Access Journals (Sweden)

Mahmoud A. F. Kaabneh

2015-01-01

Full Text Available Objective The objective of this study was to evaluate the effect of phenobarbital and phototherapy combination on the total serum bilirubin of the newborn infants with isoimmune hemolytic disease (IHD and its impact on blood exchange transfusion rates. Patients and Method This single-blinded, prospective, randomized, controlled trial was conducted between March 2013 and December 2014 at the pediatric ward of two Military Hospitals in Jordan. A total of 200 full-term neonates with IHD were divided randomly into two groups: (1 the phenobarbital plus phototherapy group ( n = 103, and (2 the phototherapy-only group ( n = 97. Infants in group 1 received an oral dose of 2.5 mg/kg phenobarbital every 12 hours for 3 days in addition to phototherapy. The total serum bilirubin was observed. Results Of the total 200 included newborn infants, 186 infants completed the study: 97 infants were included in group 1 and 89 infants in group 2. The difference between the mean total serum bilirubin levels at 24, 48, and 72 hours after starting the trial was clinically and statistically significant at P < 0.05. The differences between the two groups were also statistically significant at P < 0.05. Of the total 186 who completed the study, only 22 underwent blood exchange transfusion [7 from group 1, and 15 from group 2 ( P = 0.0478]. Conclusion In a limited-resources setting, phenobarbital in combination with phototherapy may be helpful to newborn infants with IHD, as it results in a faster decline in total serum bilirubin, thus decreasing the need for blood exchange transfusion than phototherapy alone.

Electrochemical characterization of adsorbed bilirubin oxidase on Vulcan XC 72R for the biocathode preparation in a glucose/O2 biofuel cell

International Nuclear Information System (INIS)

Habrioux, A.; Napporn, T.; Servat, K.; Tingry, S.; Kokoh, K.B.

2010-01-01

A new biocathode was built and tested. It consisted of bilirubin oxidase adsorbed on Vulcan XC 72 R and immobilized into a Nafion matrix. The possibility of direct electron transfer between bilirubin oxidase and Vulcan XC 72 R was also demonstrated. The kinetics on biocathode were enhanced by including 2,2'-azinobis-3-ethylbenzothiazoline-5-sulfonic acid in the catalytic film. A first order reaction rate was observed for oxygen concentrations lower than 22%. A complete kinetic investigation of the system was shown. A biofuel cell test performed with this biocathode and Au 70 Pt 30 nanoparticles as anode catalyst permitted to reach a power density of 170 μW cm -2 at a cell voltage of 0.6 V, which is superior to what can be obtained with the concentric design.

Cross-talk between neurons and astrocytes in response to bilirubin: adverse secondary impacts.

Science.gov (United States)

Falcão, Ana Sofia; Silva, Rui F M; Vaz, Ana Rita; Gomes, Cátia; Fernandes, Adelaide; Barateiro, Andreia; Tiribelli, Claudio; Brites, Dora

2014-07-01

Previous studies using monotypic nerve cell cultures have shown that bilirubin-induced neurological dysfunction (BIND) involves apoptosis and necrosis-like cell death, following neuritic atrophy and astrocyte activation,and that glycoursodeoxycholic acid (GUDCA) has therapeutic efficacy against BIND. Cross-talk between neurons and astrocytes may protect or aggravate neurotoxicity by unconjugated bilirubin (UCB). In a previous work we have shown that bidirectional signaling during astrocyte-neuron recognition attenuates neuronal damage by UCB. Here, we investigated whether the establishment of neuron-astrocyte homeostasis prior to cell exposure to UCB was instead associated with a lower resistance of neurons to UCB toxicity, and if the pro-survival properties of GUDCA were replicated in that experimental model. We have introduced a 24 h adaptation period for neuron-glia communication prior to the 48 h treatment with UCB. In such conditions, UCB induced glial activation, which aggravated neuronal damage, comprising increased apoptosis,cell demise and neuritic atrophy, which were completely prevented in the presence of GUDCA. Neuronal multidrug resistance-associated protein 1 expression and tumor necrosis factor-a secretion, although unchanged by UCB, increased in the presence of astrocytes. The rise in S100B and nitric oxide in the co-cultures medium may have contributed to UCB neurotoxicity. Since the levels of these diffusible molecules did not change by GUDCA we may assume that they are not directly involved in its beneficial effects. Data indicate that astrocytes, in an indirect neuron-astrocyte co-culture model and after homeostatic setting regulation of the system, are critically influencing neurodegeneration by UCB, and support GUDCA for the prevention of BIND.

Effects of delayed cord clamping on residual placental blood volume, hemoglobin and bilirubin levels in term infants: a randomized controlled trial.

Science.gov (United States)

Mercer, J S; Erickson-Owens, D A; Collins, J; Barcelos, M O; Parker, A B; Padbury, J F

2017-03-01

The objective of the study was to measure the effects of a 5-min delay (DCC) versus immediate cord clamping (ICC) on residual placental blood volume (RPBV) at birth, and hemoglobin and serum bilirubin at 24 to 48 h of age. In this prospective randomized controlled trial, 73 women with term (37 to 41 weeks) singleton fetuses were randomized to DCC (⩾5 min; n=37) or ICC (protocol violations. Cord milking was the proxy for DCC (n=11) when the provider could not wait. Infants randomized to DCC compared with ICC had significantly less RPBV (20.0 versus 30.8 ml kg -1 , Phemoglobin levels (19.4 versus 17.8 g dl -1 , P=0.002) at 24 to 48 h, with no difference in bilirubin levels. Term infants had early hematological advantage of DCC without increases in hyperbilirubinemia or symptomatic polycythemia.

Effect of Probiotics on Serum Bilirubin Level in Term Neonates with Jaundice; A Randomized Clinical Trial

OpenAIRE

Yadollah Zahed Pasha; Mousa Ahmadpour-kacho; Abes Ahmadi Jazi; Hemmat Gholinia

2017-01-01

Background In recent years, tendency to use drugs has been increasing in the treatment of neonatal jaundice. Several drugs have been used since then, but the effect of probiotics on serum bilirubin level (SBL) is not so clear. This study was conducted to evaluate the effect of probiotics on SBL and the duration of phototherapy in term neonates with hyperbilirubinemia. Materials and Methods: In this randomized clinical trial, we studied 150 term neonate with jaundice hospitalized for photother...

Essential Roles of Raf/Extracellular Signal-regulated Kinase/Mitogen-activated Protein Kinase Pathway, YY1, and Ca2+ Influx in Growth Arrest of Human Vascular Smooth Muscle Cells by Bilirubin*

Science.gov (United States)

Stoeckius, Marlon; Erat, Anna; Fujikawa, Tatsuya; Hiromura, Makoto; Koulova, Anna; Otterbein, Leo; Bianchi, Cesario; Tobiasch, Edda; Dagon, Yossi; Sellke, Frank W.; Usheva, Anny

2012-01-01

The biological effects of bilirubin, still poorly understood, are concentration-dependent ranging from cell protection to toxicity. Here we present data that at high nontoxic physiological concentrations, bilirubin inhibits growth of proliferating human coronary artery smooth muscle cells by three events. It impairs the activation of Raf/ERK/MAPK pathway and the cellular Raf and cyclin D1 content that results in retinoblastoma protein hypophosphorylation on amino acids S608 and S780. These events impede the release of YY1 to the nuclei and its availability to regulate the expression of genes and to support cellular proliferation. Moreover, altered calcium influx and calpain II protease activation leads to proteolytical degradation of transcription factor YY1. We conclude that in the serum-stimulated human vascular smooth muscle primary cell cultures, bilirubin favors growth arrest, and we propose that this activity is regulated by its interaction with the Raf/ERK/MAPK pathway, effect on cyclin D1 and Raf content, altered retinoblastoma protein profile of hypophosphorylation, calcium influx, and YY1 proteolysis. We propose that these activities together culminate in diminished 5 S and 45 S ribosomal RNA synthesis and cell growth arrest. The observations provide important mechanistic insight into the molecular mechanisms underlying the transition of human vascular smooth muscle cells from proliferative to contractile phenotype and the role of bilirubin in this transition. PMID:22262839

On the Possibility of Uphill Intramolecular Electron Transfer in Multicopper Oxidases: Electrochemical and Quantum Chemical Study of Bilirubin Oxidase

Czech Academy of Sciences Publication Activity Database

Shleev, S.; Andoralov, V.; Falk, M.; Reimann, C. T.; Ruzgas, T.; Srnec, Martin; Ryde, U.; Rulíšek, Lubomír

2012-01-01

Roč. 24, č. 7 (2012), s. 1524-1540 ISSN 1040-0397 Grant - others:7th Framework Program(XE) NMP4-SL-2009-229255 Institutional research plan: CEZ:AV0Z40550506 Keywords : bilirubin oxidase * intramolecular electron transfer * rate-limiting catalytic step * reorganization energy * QM/MM calculations Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 2.817, year: 2012

A needle extraction utilizing a molecularly imprinted-sol-gel xerogel for on-line microextraction of the lung cancer biomarker bilirubin from plasma and urine samples.

Science.gov (United States)

Moein, Mohammad Mahdi; Jabbar, Dunia; Colmsjö, Anders; Abdel-Rehim, Mohamed

2014-10-31

In the present work, a needle trap utilizing a molecularly imprinted sol-gel xerogel was prepared for the on-line microextraction of bilirubin from plasma and urine samples. Each prepared needle could be used for approximately one hundred extractions before it was discarded. Imprinted and non-imprinted sol-gel xerogel were applied for the extraction of bilirubin from plasma and urine samples. The produced molecularly imprinted sol-gel xerogel polymer showed high binding capacity and fast adsorption/desorption kinetics for bilirubin in plasma and urine samples. The adsorption capacity of molecularly imprinted sol-gel xerogel polymer was approximately 60% higher than that of non-imprinted polymer. The effect of the conditioning, washing and elution solvents, pH, extraction time, adsorption capacity and imprinting factor were investigated. The limit of detection and the lower limit of quantification were set to 1.6 and 5nmolL(-1), respectively using plasma or urine samples. The standard calibration curves were obtained within the concentration range of 5-1000nmolL(-1) in both plasma and urine samples. The coefficients of determination values (R(2)) were ≥0.998 for all runs. The extraction recovery was approximately 80% for BR in the human plasma and urine samples. Copyright © 2014 Elsevier B.V. All rights reserved.

Study on dioxygen reduction by mutational modifications of the hydrogen bond network leading from bulk water to the trinuclear copper center in bilirubin oxidase

International Nuclear Information System (INIS)

Morishita, Hirotoshi; Kurita, Daisuke; Kataoka, Kunishige; Sakurai, Takeshi

2014-01-01

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

Study on dioxygen reduction by mutational modifications of the hydrogen bond network leading from bulk water to the trinuclear copper center in bilirubin oxidase

Energy Technology Data Exchange (ETDEWEB)

Morishita, Hirotoshi; Kurita, Daisuke; Kataoka, Kunishige; Sakurai, Takeshi, E-mail: tsakurai@se.kanazawa-u.ac.jp

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.

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

Science.gov (United States)

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.

Evaluation of Treatment Thresholds for Unconjugated Hyperbilirubinemia in Preterm Infants: Effects on Serum Bilirubin and on Hearing Loss?

OpenAIRE

Hulzebos, Christian V.; van Dommelen, Paula; Verkerk, Paul H.; Dijk, Peter H.; Van Straaten, Henrica L. M.

2013-01-01

Background:Severe unconjugated hyperbilirubinemia may cause deafness. In the Netherlands, 25% lower total serum bilirubin (TSB) treatment thresholds were recently implemented for preterm infants.Objective:To determine the rate of hearing loss in jaundiced preterms treated at high or at low TSB thresholds.Design/Methods:In this retrospective study conducted at two neonatal intensive care units in the Netherlands, we included preterms (gestational age 35 dB).Results:There were 479 patients in t...

The Evolving Landscape of Neurotoxicity by Unconjugated Bilirubin: Role of Glial Cells and Inflammation

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Dora eBrites

2012-05-01

Full Text Available Unconjugated hyperbilirubinemia is a common condition in the first week of postnatal life. Although generally harmless, some neonates may develop very high levels of unconjugated bilirubin (UCB, which may surpass the protective mechanisms of the brain at preventing UCB accumulation. In this case, both short-term and long-term neurodevelopmental disabilities, such as acute and chronic UCB encephalopathy, known as kernicterus, or more subtle alterations designed as bilirubin-induced neurological dysfunction (BIND may be produced. There is a tremendous variability in babies’ vulnerability towards UCB for reasons not yet explained, but preterm birth, sepsis, hypoxia and haemolytic disease are comprised as risk factors. Therefore, UCB levels and neurological abnormalities are not strictly correlated. Even nowadays, the mechanisms of UCB neurotoxicity are still unclear, as are specific biomarkers, and little is known about lasting sequelae attributable to hyperbilirubinemia. On autopsy, UCB was shown to be within neurons, neuronal processes and microglia, and to produce loss of neurons, demyelination and gliosis. In isolated cell cultures, UCB was shown to impair neuronal arborization and to induce the release of proinflammatory cytokines from microglia and astrocytes. However, cell dependent-sensitivity to UCB toxicity and the role of each nerve cell type remain understood. This review provides a comprehensive insight into cell susceptibilities and molecular targets of UCB in neurons, astrocytes, and oligodendrocytes, and on phenotypic and functional responses of microglia to UCB. Interplay among glia elements and cross-talk with neurons, with a special emphasis in the UCB-induced immunostimulation, and the role of sepsis in BIND pathogenesis are highlighted. New and interesting data on the anti-inflammatory and antioxidant activities of different pharmacological agents are also presented, as novel and promising additional therapeutic approaches to

THE ASSOCIATION BETWEEN G6PD DEFICIENCY AND TOTAL SERUM BILIRUBIN LEVEL IN ICTERIC NEONATES

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S. Behjati-Ardakani

2007-07-01

Full Text Available "nGlucose-6-phosphate dehydrogenase (G6PD deficiency is the most important disease of the hexose monophosphate pathway. Deficiency of this enzym can lead to hemolysis of red blood cells. Our aim was to study the prevalence of G6PD deficiency in relation to neonatal jaundice. We studied 456 clinically icteric neonates Laboratory investigations included determination of direct and indirect serum bilirubin concentrations, blood group typing, direct coomb's test, hemoglobin, blood smear, reticulocyte count and G6PD level. We divided these neonates to 3 groups based on total serum bilirubin level (TSB: TSB< 20 mg%, TSB=20-25 mg%, and TSB>25 mg%. In only 35 (7.6% of cases G6PD deficiency was diagnosed. All of these babies were male. From 456 icteric neonates, 213 cases belong to group 1 (TSB<20 mg%, 158 cases belong to group 2 (TSB=20-25 mg% and 85 cases belong to group 3 (TSB>25 mg%. 16 neonates from 213 neonates of group 1, 6 neonates from 158 neonates of group 2 and 13 neonates from 85 neonates of group 3 had G6PD deficiency. There was statistically significant difference of prevalence of G6PD deficiency between group 2 and 3 ( 15.3% vs 3.8%( P = 0.001. Between groups 1 vs 2 and 1 vs 3 no statistically significant difference was found. Early detection of this enzymopathy regardless of sex and close surveillance of the affected newborns may be important in reducing the risk of severe hyperbilirubinemia. This emphasizes the necessity of neonatal screening on cord blood samples for G6PD deficiency.

Pulse radiolytic and spectrophotometric investigation of the binding of bilirubin to bovine serum albumin

International Nuclear Information System (INIS)

Adhikari, S.; Guha, S.N.; Gopinathan, C.

1994-01-01

Bilirubin (BR) exhibits marked change in its absorption properties in the presence of bovine serum albumin (BSA). The λ max of BR observed at 440 nm is red shifted by about 20 nm with 8% increase in band intensity when BSA is present in the matrix. Medium polarity and salt effects were also studied in this system and it was inferred that BR is bound to BSA to form a complex, which becomes unstable at high salt concentration or in a medium of low dielectric constant such as water-alcohol mixture. Pulse radiolysis study of this system employing CO 2 .- radical revealed that BR blocks the sites of CO 2 .- attack in the BSA molecule. (author). 3 refs., 2 figs

Predictive value of cord blood bilirubins for hyperbilirubinemia in neonates at risk for maternal-fetal blood group incompatibility and hemolytic disease of the newborn

Science.gov (United States)

Calkins, Kara L.; Roy, Devika; Molchan, Lauren; Bradley, Lyndsey; Grogan, Tristan; Elashoff, David; Walker, Valencia P.

2015-01-01

Objective To determine the predictive ability of cord blood bilirubin (CBB) for hyperbilirubinemia in a population at risk for maternal-fetal blood group incompatibility and hemolytic disease of the newborn. Study Design This is a single center retrospective case-control study. Cases received phototherapy; controls did not. Cases were matched 1:3 to controls by gender and treating physician. Inclusion criteria included: ≥ 35 weeks gestation, CBB, and one or more total serum bilirubin (TSB) concentrations. The primary outcome was CBB. Secondary outcomes were a TSB > 75th percentile, length of stay, and neonatal intensive care unit admission. The prognostic ability of CBB for phototherapy and TSB > 75th percentile was assessed using area under the receiver operating characteristic (ROC) curve. Logistic regression analyses were performed to determine predictors for phototherapy and TSB > 75th percentile. Result When compared to controls (n=142), cases (n=54) were more likely to have a positive Coombs’ test (82% vs. 41%, p 75th percentile (85% vs. 21%, p75th percentile was 0.87±0.03 (phemolytic disease of the newborn. PMID:26518407

Predictive value of cord blood bilirubin for hyperbilirubinemia in neonates at risk for maternal-fetal blood group incompatibility and hemolytic disease of the newborn.

Science.gov (United States)

Calkins, K; Roy, D; Molchan, L; Bradley, L; Grogan, T; Elashoff, D; Walker, V

2015-01-01

To determine the predictive ability of cord blood bilirubin (CBB) for hyperbilirubinemia in a population at risk for maternal-fetal blood group incompatibility and hemolytic disease of the newborn. This is a single center retrospective case-control study. Cases received phototherapy; controls did not. Cases were matched 1:3 to controls by gender and treating physician. Inclusion criteria included: ≥35 weeks gestation, CBB, and one or more total serum bilirubin (TSB) concentrations. The primary outcome was CBB. Secondary outcomes were a TSB >75th percentile, length of stay, and neonatal intensive care unit admission. The prognostic ability of CBB for phototherapy and TSB >75th percentile was assessed using area under the receiver operating characteristic (ROC) curve. Logistic regression analyses were performed to determine predictors for phototherapy and TSB >75th percentile. When compared to controls (n = 142), cases (n = 54) were more likely to have a positive Coombs' test (82% vs. 41% , p 75th percentile (85% vs. 21% , p 75th percentile was 0.87 ± 0.03 (p hemolytic disease of the newborn.

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

Science.gov (United States)

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.

Selected Abstracts of the 2nd Congress of joint European Neonatal Societies (jENS 2017; Venice (Italy; October 31-November 4, 2017; Session "Neonatal Hematology and Bilirubin"

Directory of Open Access Journals (Sweden)

--- Various Authors

2017-10-01

Full Text Available Selected Abstracts of the 2nd Congress of joint European Neonatal Societies (jENS 2017; Venice (Italy; October 31-November 4, 201758th ESPR Annual Meeting, 7th International Congress of UENPS, 3rd International Congress of EFCNIORGANIZING INSTITUTIONSEuropean Society for Paediatric Research (ESPR, European Society for Neonatology (ESN, Union of European Neonatal & Perinatal Societies (UENPS, European Foundation for the Care of Newborn Infants (EFCNIORGANIZING COMMITTEELuc Zimmermann (President of ESPR, Morten Breindahl (President of ESN, Manuel Sánchez Luna (President of UENPS, Silke Mader (Chairwoman of the Executive Board and Co-Founder of EFCNISCIENTIFIC COMMITTEEVirgilio P. Carnielli (Congress President Chair, Pierre Gressens (Past Scientific President, Umberto Simeoni, Manon Benders, Neil Marlow, Ola D. Saugstad, Petra Hüppi, Agnes van den HoogenSession "Neonatal Hematology and Bilirubin"ABS 1. PROLONGED JAUNDICE SCREENING: FULL BLOOD COUNT (FBC OR NO FBC! • N. Storring, R. Doherty, V. PonnusamyABS 2. EFFECT OF PROBIOTIC SUPPLEMENTATION ON BREAST MILK JAUNDICE • N. Koksal, O. Bagcı, H. Ozkan, I. Varal, P. DoganABS 3. LABORATORY FINDINGS, DIAGNOSIS AND TREATMENT OF THE NEWBORN ADMITTED DUE TO HEMATEMESIS OR BLOODY STOOL IN 11 YEARS • I. Hokuto, Y. Ito, T. Mori, S. KomachiABS 4. AN UNUSUAL CAUSE OF CYANOSIS: SEVERE METHEMOGLOBINEMIA IN A PRETERM INFANT WITH SEPSIS • F. Bakar, M. BerberABS 5. THE INFLUENCE OF INTRAUTERINE TRANSFUSION ON THE OUTCOMES OF NEWBORNS WITH SEVERE HEMOLYTIC DISEASE • E. Balashova, O. Bystrykh, T. Fedorova, O. Ionov, A. Kirtbaya, D. Sharafutdinova, V. Zubkov, D. Degtyarev, O. Horoshkeeva, N. Fedorova, N. Tetruashvili, K. Kostukov, N. KaretnikovaABS 6. PATCHED SKIN BILIRUBIN ASSAY TO MONITOR EXTREMELY PRETERM NEONATES UNDERGOING PHOTOTHERAPY • D. De Luca, V. Dell’OrtoABS 7. A PRETERM MODEL OF HYPERBILIRUBINEMIA-INDUCED CEREBELLAR DYSFUNCTION • C.F. Bearer, M. He, J.F. Watchko, J.M. Simard, N. Tang

Lysozyme and bilirubin bind to ACE and regulate its conformation and shedding

Science.gov (United States)

Danilov, Sergei M.; Lünsdorf, Heinrich; Akinbi, Henry T.; Nesterovitch, Andrew B.; Epshtein, Yuliya; Letsiou, Eleftheria; Kryukova, Olga V.; Piegeler, Tobias; Golukhova, Elena Z.; Schwartz, David E.; Dull, Randal O.; Minshall, Richard D.; Kost, Olga A.; Garcia, Joe G. N.

2016-01-01

Angiotensin I-converting enzyme (ACE) hydrolyzes numerous peptides and is a critical participant in blood pressure regulation and vascular remodeling. Elevated tissue ACE levels are associated with increased risk for cardiovascular and respiratory disorders. Blood ACE concentrations are determined by proteolytic cleavage of ACE from the endothelial cell surface, a process that remains incompletely understood. In this study, we identified a novel ACE gene mutation (Arg532Trp substitution in the N domain of somatic ACE) that increases blood ACE activity 7-fold and interrogated the mechanism by which this mutation significantly increases blood ACE levels. We hypothesized that this ACE mutation disrupts the binding site for blood components which may stabilize ACE conformation and diminish ACE shedding. We identified the ACE-binding protein in the blood as lysozyme and also a Low Molecular Weight (LMW) ACE effector, bilirubin, which act in concert to regulate ACE conformation and thereby influence ACE shedding. These results provide mechanistic insight into the elevated blood level of ACE observed in patients on ACE inhibitor therapy and elevated blood lysozyme and ACE levels in sarcoidosis patients. PMID:27734897

Fabrication of high performance bioanode based on fruitful association of dendrimer and carbon nanotube used for design O2/glucose membrane-less biofuel cell with improved bilirubine oxidase biocathode.

Science.gov (United States)

Korani, Aazam; Salimi, Abdollah

2013-12-15

In this study, the preparation of an integrated modified electrode based on the covalent attachment of glucose dehydrogenase (GDH) enzyme and safranin O to amine-derivative multiwalled carbon nanotubes (MWCNTs-NH2) modified glassy carbon (GC) electrode using G2.5-carboxylated PAMAM dendrimer (Den) as linking agent is reported. The obtained results indicated that the proposed system has effective bioelectrocatalytic activity toward glucose oxidation at 100 mV with onset potential of -130 mV (vs. Ag/AgCl). The performance of the prepared hybrid system of GC/MWCNTs-NH2/Den/GDH/Safranin as anode in a membraneless enzyme-based glucose/O2 biofuel cell is further evaluated. The biocathode in this system was composed of bilirubin oxidase (BOX) enzyme immobilized onto a bilirubin modified carbon nanotube GC electrode. Immobilized BOX onto CNTs/bilirubin not only show direct electron transfer but also it has excellent electrocatalytic activity toward oxygen reduction at a positive potential of 610 mV. The open circuit voltage of the cell was 590 mV. The maximum current density was 0.5 mA cm(-2), while maximum power density of 108 μW cm(-2) was achieved at voltage of 330 mV. The immobilized enzymes in anode and cathode are very stable and output power of the BFC is approximately constant after 12 h continues operation. Copyright © 2013 Elsevier B.V. All rights reserved.

Preparation and surface properties of mesoporous silica particles modified with poly(N-vinyl-2-pyrrolidone) as a potential adsorbent for bilirubin removal

Energy Technology Data Exchange (ETDEWEB)

Timin, Alexander, E-mail: a_timin@mail.ru [Inorganic Chemistry Department, Ivanovo State University of Chemistry and Technology (ISUCT), 7, Sheremetevsky prosp., 153000 Ivanovo (Russian Federation); Rumyantsev, Evgeniy, E-mail: evr@isuct.ru [Inorganic Chemistry Department, Ivanovo State University of Chemistry and Technology (ISUCT), 7, Sheremetevsky prosp., 153000 Ivanovo (Russian Federation); Lanin, Sergey N., E-mail: SNLanin@phys.chem.msu.ru [Chemistry Department, Physical Chemistry Division, Lomonosov Moscow State University, 1-3 Leninskie Gory, 119991 Moscow (Russian Federation); Rychkova, Sveta A. [Chemistry Department, Physical Chemistry Division, Lomonosov Moscow State University, 1-3 Leninskie Gory, 119991 Moscow (Russian Federation); Guseynov, Sabir S. [Krestov Institute of Solution Chemistry of Russian Academy of Sciences, 153000 Ivanovo (Russian Federation); Solomonov, Alexey V. [Inorganic Chemistry Department, Ivanovo State University of Chemistry and Technology (ISUCT), 7, Sheremetevsky prosp., 153000 Ivanovo (Russian Federation); Antina, Elena V. [Krestov Institute of Solution Chemistry of Russian Academy of Sciences, 153000 Ivanovo (Russian Federation)

2014-10-15

The surface of silica particles was modified with polyvinyl pyrrolidone (PVP) through sol–gel process. The different experimental techniques, i.e., thermogravimetric analysis (TGA and DTG), nitrogen adsorption, scanning electron microscopy (SEM), laser diffraction analysis (LDA), fourier transform spectroscopy (FTIR) are used to characterize the pure non-functionalized and functionalized silicas containing different amount of PVP. It was shown that PVP-modified silica samples have well developed porous structure; the values of specific surface area for PVP-modified silicas are in the range of 140–264 m{sup 2} g{sup −1}. While the non-functionalized silica shows the low surface area (S{sub BET} = 40 m{sup 2} g{sup −1}). The BJH analysis showed that PVP can be used as an effective agent to increase an average pore size and total pore volume. The results indicate that PVP functionalized silicas show a potential as effective adsorbents for bilirubin removal compared to other available adsorbents. - Highlights: • PVP functionalized silicas were synthesized via sol–gel method. • Modification of silica by PVP leads to the formation of mesoporous structure. • PVP functionalized mesoporous silicas demonstrate good adsorption properties for bilirubin removal.

Mechanisms of redox interactions of bilirubin with copper and the effects of penicillamine.

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Božić, Bojana; Korać, Jelena; Stanković, Dalibor M; Stanić, Marina; Popović-Bijelić, Ana; Bogdanović Pristov, Jelena; Spasojević, Ivan; Bajčetić, Milica

2017-12-25

Toxic effects of unconjugated bilirubin (BR) in neonatal hyperbilirubinemia have been related to redox and/or coordinate interactions with Cu 2+ . However, the development and mechanisms of such interactions at physiological pH have not been resolved. This study shows that BR reduces Cu 2+ to Cu 1+ in 1:1 stoichiometry. Apparently, BR undergoes degradation, i.e. BR and Cu 2+ do not form stable complexes. The binding of Cu 2+ to inorganic phosphates, liposomal phosphate groups, or to chelating drug penicillamine, impedes redox interactions with BR. Cu 1+ undergoes spontaneous oxidation by O 2 resulting in hydrogen peroxide accumulation and hydroxyl radical production. In relation to this, copper and BR induced synergistic oxidative/damaging effects on erythrocytes membrane, which were alleviated by penicillamine. The production of reactive oxygen species by BR and copper represents a plausible cause of BR toxic effects and cell damage in hyperbilirubinemia. Further examination of therapeutic potentials of copper chelators in the treatment of severe neonatal hyperbilirubinemia is needed. Copyright © 2017 Elsevier B.V. All rights reserved.

Preoperative Albumin-Bilirubin Grade Predicts Recurrences After Radical Gastrectomy in Patients with pT2-4 Gastric Cancer.

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Kanda, Mitsuro; Tanaka, Chie; Kobayashi, Daisuke; Uda, Hiroaki; Inaoka, Kenichi; Tanaka, Yuri; Hayashi, Masamichi; Iwata, Naoki; Yamada, Suguru; Fujii, Tsutomu; Sugimoto, Hiroyuki; Murotani, Kenta; Fujiwara, Michitaka; Kodera, Yasuhiro

2018-03-01

The albumin-bilirubin (ALBI) score was initially developed for assessing liver dysfunction severity and was suggested to have prognostic value in patients with hepatocellular carcinoma. We aimed to evaluate the prognostic impact of ALBI grade in patients with advanced gastric cancer (GC) after radical gastrectomy. This study included 283 patients who underwent radical gastrectomy for pT2-4 GC without preoperative treatment. ALBI was calculated as follows: (log 10 bilirubin (μmol/L) × 0.66) + (albumin (g/L) × -0.0852) and categorized into grades 1 (≤-2.60), 2 (-2.60<, ≤-1.39) and 3 (-1.39<). The median ALBI score was -2.96, and a number of patients in ALBI grades 1, 2 and 3 were 228, 55 and 0, respectively. Patients with ALBI grade 2 had a lower administration rate of adjuvant chemotherapy than those with ALBI grade 1, whereas no significant differences were found in morbidity rate and disease stage. The ALBI grade 2 group was more likely to have shorter disease-specific and disease-free survival compared with the ALBI grade 1 group. Multivariable analysis identified ALBI grade 2 as an independent prognostic factor for disease-free survival (hazard ratio 1.97, 95% confidence interval 1.10-3.47, p = 0.0242). Survival differences between ALBI grade 1 and 2 groups were increased in the patient subset that received adjuvant chemotherapy. ALBI grade 2 was correlated with a shortened duration of administration of postoperative S-1 adjuvant. ALBI grade serves as a simple and promising predictive factor for disease-free and disease-specific survival in patients with pT2-4 GC after radical gastrectomy.

Decolorization and biodegradation of remazol brilliant blue R by bilirubin oxidase.

Science.gov (United States)

Liu, Youxun; Huang, Juan; Zhang, Xiaoyu

2009-12-01

The dye-decolorizing potential of bilirubin oxidase (BOX) was demonstrated for an anthraquinone dye, remazol brilliant blue R (RBBR). The dye was decolorized 40% within 4 h by the BOX alone, whereas it was more efficient in the presence of 2, 2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), showing 91.5% decolorization within 25 min. The effects of operational parameters on decolorization were examined. The results showed that the decolorization efficiency decreased with increasing RBBR concentration, and a marked inhibition effect was exhibited when the dye concentrations were above 100 mg l(-1). The optimum temperature for enzymatic decolorization was 40 degrees C. BOX showed efficient decolorization of the dye with a wide pH range of 5-8.5. The maximum decolorization activity occurred at pH 8 with ABTS and at pH 5 without ABTS. Analysis of RBBR ultraviolet and visible (UV-VIS) spectra after BOX treatment indicated that the decolorization of RBBR was due to biodegradation. Our results suggested that ABTS can serve as an electron mediator to facilitate the oxidation of RBBR, and the BOX-ABTS mediator-involved dye decolorization mechanism was similar to that of laccase. Operation over a wide range of pH and efficient decolorization suggested that the BOX can be used to decolorize synthetic dyes from effluents, especially for anthraquinonic dyes.

Photophysics of the variable quantum yield of asymmetric bilirubin

International Nuclear Information System (INIS)

Troup, G.J.

1998-01-01

Full text: Bilirubin (BR), responsible for neonatal jaundice, is a molecule containing two pyrromethenone chromophores conjoined by a 'saturated' carbon CH 2 group. Because this disease is cured by phototherapy, BR has been extensively studied by laser means. When the chromophores in each half of the molecule are identical, we have symmetrical BR (SBR); when they are not, we have asymmetric BR (ASBR). The quantum yield of the photoproducts in simple organic solution from SBR is not wavelength-dependent, while that from ASBR is. Because of the proximity of the two chromophores, both the SBR and ASBR systems are subject to Davidoff (dynamic electric dipole) splitting of the chromophore excited states. A quantum mechanical calculation shows that when the two (ASBR) chromophore states are not degenerate, the higher Davidoff state is preferentially occupied by the chromophore with the 'original' higher energy, and the lower Davidoff state by the chromophore of 'original' lower energy. This is just what is required for the quantum yield to vary with wavelength. If the variation of the quantum yield of ASBR in the presence of human serum albumen is approximated by a square-wave (narrow line approximation), the deduced ratio of the short wavelength photoproduct yield with the long wavelength one is in agreement with accepted values for the 'original' energy difference of the chromophores, and the Davidoff splitting parameter. A previous explanation has involved variation of relaxation processes with wavelength, but only qualitatively. The quantum yields for SBRs bonded to HSA are not yet published, but show wavelength variation, possibly from asymmetric bonding. In 0.1% ammonia/methanol however, there is no such variation for the SBRs, while for ASBR, there is, and the photoproduct ratios for long and short wavelength are reciprocals of one another, as predicted by our theory

Electrochemical pretreatment of amino-carbon nanotubes on graphene support as a novel platform for bilirubin oxidase with improved bioelectrocatalytic activity towards oxygen reduction.

Science.gov (United States)

Navaee, Aso; Salimi, Abdollah; Jafari, Fereydoon

2015-03-23

The electrochemical conditioning of amino-carbon nanotubes (CNTs) on a graphene support in an alkaline solution is used to produce -NHOH as hydrophilic functional groups for the efficient immobilization of bilirubin oxidase enzyme. The application of the immobilized enzyme for the direct electrocatalytic reduction of O2 is investigated. The onset potential of 0.81 V versus NHE and peak current density of 2.3 mA cm(-2) for rotating modified electrode at 1250 rpm, indicate improved biocatalytic activity of the proposed system for O2 reduction. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Modulation of defect-mediated energy transfer from ZnO nanoparticles for the photocatalytic degradation of bilirubin

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Tanujjal Bora

2013-11-01

Full Text Available In recent years, nanotechnology has gained significant interest for applications in the medical field. In this regard, a utilization of the ZnO nanoparticles for the efficient degradation of bilirubin (BR through photocatalysis was explored. BR is a water insoluble byproduct of the heme catabolism that can cause jaundice when its excretion is impaired. The photocatalytic degradation of BR activated by ZnO nanoparticles through a non-radiative energy transfer pathway can be influenced by the surface defect-states (mainly the oxygen vacancies of the catalyst nanoparticles. These were modulated by applying a simple annealing in an oxygen-rich atmosphere. The mechanism of the energy transfer process between the ZnO nanoparticles and the BR molecules adsorbed at the surface was studied by using steady-state and picosecond-resolved fluorescence spectroscopy. A correlation of photocatalytic degradation and time-correlated single photon counting studies revealed that the defect-engineered ZnO nanoparticles that were obtained through post-annealing treatments led to an efficient decomposition of BR molecules that was enabled by Förster resonance energy transfer.

Efficient Photocatalytic Bilirubin Removal over the Biocompatible Core/Shell P25/g-C3N4 Heterojunctions with Metal-free Exposed Surfaces under Moderate Green Light Irradiation

Science.gov (United States)

Kang, Shifei; Qin, Hengfei; Zhang, Lu; Huang, Yongkui; Bai, Xia; Li, Xi; Sun, Di; Wang, Yangang; Cui, Lifeng

2017-03-01

Highly-monodispersed g-C3N4/TiO2 hybrids with a core/shell structure were synthesized from a simple room temperature impregnation method, in which g-C3N4 was coated through self-assembly on the commercially available Degussa P25 TiO2 nanoparticles. Structural and surface characterizations showed that the presence of g-C3N4 notably affected the light absorption characteristics of TiO2. The g-C3N4/TiO2 heterojunctions with metal-free exposed surfaces were directly used as biocompatible photocatalysts for simulated jaundice phototherapy under low-power green-light irradiation. The photocatalytic activity and stability of g-C3N4/TiO2 were enhanced relative to pure P25 or g-C3N4, which could be ascribed to the effective Z-scheme separation of photo-induced charge carriers in g-C3N4/TiO2 heterojunction. The photoactivity was maximized in the 4 wt.% g-C3N4-coated P25, as the bilirubin removal rate under green light irradiation was more than 5-fold higher than that under the clinically-used blue light without any photocatalyst. This study approves the future applications of the photocatalyst-assisted bilirubin removal in jaundice treatment under moderate green light which is more tolerable by humans.

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

Science.gov (United States)

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.

Research Update: Facile synthesis of CoFe2O4 nano-hollow spheres for efficient bilirubin adsorption

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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.

Cross-Sectional and Longitudinal Associations between Serum Bilirubin and Prediabetes in a Health Screening Population.

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Oda, Eiji

2016-06-01

Longitudinal associations between total bilirubin (TB) and prediabetes have not been reported. This study investigated cross-sectional and longitudinal associations between TB and prediabetes. Cross-sectional associations between TB and prediabetes were investigated in 3681 nondiabetic subjects. Longitudinal associations between TB and prediabetes over 6 years were investigated in 2149 subjects who were normoglycemic at baseline. Prediabetes was defined as fasting plasma glucose (FPG) levels of ≥5.6 mmol/L or glycated hemoglobin levels of ≥5.7% excluding diabetes. The prevalence of prediabetes was 25.4%, and the cumulative incidence of prediabetes during 6 years was 25.5% in a Japanese health screening population. Prevalent prediabetes was significantly associated with the quintiles of TB in nonsmoking men (trend, pprediabetes was not significantly associated with the quintiles of TB, while it was positively associated with 1 standard deviation increase in TB in nonsmoking men (hazard ratio [95% confidence interval]; 1.21 [1.07 to 1.37], p=0.002). TB levels were significantly inversely associated with prevalent prediabetes in nonsmokers, but not in smokers, whereas an inverse association between TB levels and incident prediabetes seemed to be unlikely. Copyright © 2016 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.

Lack of utility of measuring serum bilirubin concentration in distinguishing perforation status of pediatric appendicitis.

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Bonadio, William; Bruno, Santina; Attaway, David; Dharmar, Logesh; Tam, Derek; Homel, Peter

2017-06-01

Pediatric appendicitis is a common, potentially serious condition. Determining perforation status is crucial to planning effective management. Determine the efficacy of serum total bilirubin concentration [STBC] in distinguishing perforation status in children with appendicitis. Retrospective review of 257 cases of appendicitis who received abdominal CT scan and measurement of STBC. There were 109 with perforation vs 148 without perforation. Although elevated STBC was significantly more common in those with [36%] vs without perforation [22%], the mean difference in elevated values between groups [0.1mg/dL] was clinically insignificant. Higher degrees of hyperbilirubinemia [>2mg/dL] were rarely encountered [5%]. Predictive values for elevated STBC in distinguishing perforation outcome were imprecise [sensitivity 38.5%, specificity 78.4%, PPV 56.8%, NPV 63.4%]. ROC curve analysis of multiple clinical and other laboratory factors for predicting perforation status was unenhanced by adding the STBC variable. Specific analysis of those with perforated appendicitis and percutaneously-drained intra-abdominal abscess which was culture-positive for Escherichia coli showed an identical rate of STBC elevation compared to all with perforation. The routine measurement of STBC does not accurately distinguish perforation status in children with appendicitis, nor discern infecting organism in those with perforation and intra-abdominal abscess. Copyright © 2017 Elsevier Inc. All rights reserved.

Modulation of Mrp1 (ABCc1 and Pgp (ABCb1 by bilirubin at the blood-CSF and blood-brain barriers in the Gunn rat.

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Silvia Gazzin

2011-01-01

Full Text Available Accumulation of unconjugated bilirubin (UCB in the brain causes bilirubin encephalopathy. Pgp (ABCb1 and Mrp1 (ABCc1, highly expressed in the blood-brain barrier (BBB and blood-cerebrospinal fluid barrier (BCSFB respectively, may modulate the accumulation of UCB in brain. We examined the effect of prolonged exposure to elevated concentrations of UCB on expression of the two transporters in homozygous, jaundiced (jj Gunn rats compared to heterozygous, not jaundiced (Jj littermates at different developmental stages (2, 9, 17 and 60 days after birth. BBB Pgp protein expression was low in both jj and Jj pups at 9 days (about 16-27% of adult values, despite the up-regulation in jj animals (2 and 1.3 fold higher than age matched Jj animals at P9 and P17-P60, respectively; Mrp1 protein expression was barely detectable. Conversely, at the BCSFB Mrp1 protein expression was rather high (60-70% of the adult values in both jj and Jj at P2, but was markedly (50% down-regulated in jj pups starting at P9, particularly in the 4(th ventricle choroid plexuses: Pgp was almost undetectable. The Mrp1 protein down regulation was accompanied by a modest up-regulation of mRNA, suggesting a translational rather than a transcriptional inhibition. In vitro exposure of choroid plexus epithelial cells obtained from normal rats to UCB, also resulted in a down-regulation of Mrp1 protein. These data suggest that down-regulation of Mrp1 protein at the BSCFB, resulting from a direct effect of UCB on epithelial cells, may impact the Mrp1-mediated neuroprotective functions of the blood-cerebrospinal fluid barrier and actually potentiate UCB neurotoxicity.

Total bilirubin in nasogastric aspirates: A potential new indicator of postoperative gastrointestinal recovery

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Go Miyano

2013-01-01

Full Text Available Background: The aim of our study was to investigate if total bilirubin (T-bil, amylase (Amy, and sodium (Na in nasogastric (NG aspirates can reflect gastrointestinal motility reliably. Materials and Methods: NG aspirates from all laparotomies lasting more than 150 min in children less than 12 months old were studied for 3 months. Color of aspirates and intensity of bowel sounds were graded every 3 h by nursing staff and aspirate samples for measuring T-bil, Amy, and Na were collected independently every 12 h until an oral fluid challenge was tolerated. Results: There were 26 subjects. Mean age at surgery was 5.6 months; mean body weight at surgery was 5.8 kg. No postoperative complications occurred. While there was no reduction in average volume of NG aspirates, color change was subjective, and bowel sounds could not be standardized, T-bil decreased over time (0d: 4.4 mg/dL; 0.5d: 2.7 mg/dL; 1.0d: 1.6 mg/dL; 1.5d: 1.3 mg/dL; 2.0d: 0.4 mg/dL; 2.5d: 0.33 mg/dL; 3.0d: 0.21 mg/dL; 3.5d: 0.15 mg/dL; 4.0d: 0.06 mg/dL; 4.5d: 0.05 mg/dL; 5.0d: 0.02 mg/dL; 5.5d: 0.02 mg/dL; 6.0d: 0.01 mg/dL. Amy and Na were inconclusive. Conclusion: T-bil levels in NG aspirates may be useful as a reliable objective quantitative marker of gastrointestinal motility postoperatively.

Detecting paraprotein interference on a direct bilirubin assay by reviewing the photometric reaction data.

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García-González, Elena; Aramendía, Maite; González-Tarancón, Ricardo; Romero-Sánchez, Naiara; Rello, Luis

2017-07-26

The direct bilirubin (D-Bil) assay on the AU Beckman Coulter instrumentation can be interfered by paraproteins, which may result in spurious D-Bil results. In a previous work, we took advantage of this fact to detect this interference, thus helping with the identification of patients with unsuspected monoclonal gammopathies. In this work, we investigate the possibility to detect interference based on the review of the photometric reactions, regardless of the D-Bil result. The D-Bil assay was carried out in a set of 2164 samples. It included a group of 164 samples with paraproteins (67 of which caused interference on the assay), as well as different groups of samples for which high absorbance background readings could also be expected (i.e. hemolyzed, lipemic, or icteric samples). Photometric reaction data were reviewed and receiver operating characteristics (ROC) curves were used to establish a cut-off for absorbance that best discriminates interference. The best cut-off was 0.0100 for the absorbance at the first photometric point of the complementary wavelength in the blank cuvette. Once the optimal cut-off for probable interference was selected, all samples analyzed in our laboratory that provided absorbance values above this cut-off were further investigated to try to discover paraproteins. During a period of 6 months, we detected 44 samples containing paraproteins, five of which belonged to patients with non-diagnosed monoclonal gammopathies. Review of the photometric reaction data permits the systematic detection of paraprotein interference on the D-Bil AU assay, even for samples for which reasonable results are obtained.

Effects of UV light alone and in combination with phenobarbital on bilirubin concentration in serum and on bromosulfophthalein elimination from blood as well as cytochrome P 450-dependent biotransformation reactions in rats

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Ankermann, K.J.; Klinger, W.; Mueller, D.

1979-01-01

In studying the effects of UV light alone and combined with the phenobarbital inductor, a shortening of the barbital and hexobarbital lateral position time, a lowering of the bilirubin concentration and an acceleration of the bromosulfophthalein (BSP) clearance could be revealed. Effects not accompanied with an increase of biotransformation reactions such as cytochrome P 450 concentration in liver microsomes and binding of BSP on cytoplasmic acceptor proteins Y and Z of the liver as well as the amidopyridine N demethylation remained unchanged

A self-powered glucose biosensor based on pyrolloquinoline quinone glucose dehydrogenase and bilirubin oxidase operating under physiological conditions.

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Kulkarni, Tanmay; Slaughter, Gymama

2017-07-01

A novel biosensing system capable of simultaneously sensing glucose and powering portable electronic devices such as a digital glucometer is described. The biosensing system consists of enzymatic glucose biofuel cell bioelectrodes functionalized with pyrolloquinoline quinone glucose dehydrogenase (PQQ-GDH) and bilirubin oxidase (BOD) at the bioanode and biocathode, respectively. A dual-stage power amplification circuit is integrated with the single biofuel cell to amplify the electrical power generated. In addition, a capacitor circuit was incorporated to serve as the transducer for sensing glucose. The open circuit voltage of the optimized biofuel cell reached 0.55 V, and the maximum power density achieved was 0.23 mW/ cm 2 at 0.29 V. The biofuel cell exhibited a sensitivity of 0.312 mW/mM.cm 2 with a linear dynamic range of 3 mM - 20 mM glucose. The overall self-powered glucose biosensor is capable of selectively screening against common interfering species, such as ascorbate and urate and exhibited an operational stability of over 53 days, while maintaining 90 % of its activity. These results demonstrate the system's potential to replace the current glucose monitoring devices that rely on external power supply, such as a battery.

The activation of autophagy protects neurons and astrocytes against bilirubin-induced cytotoxicity.

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Qaisiya, Mohammed; Mardešić, Paula; Pastore, Beatrice; Tiribelli, Claudio; Bellarosa, Cristina

2017-11-20

Unconjugated bilirubin (UCB) neurotoxicity involves oxidative stress, calcium signaling and ER-stress. The same insults can also induce autophagy, a process of "self-eating", with both a pro-survival or a pro-apoptotic role. Our aim was to study the outcome of autophagy activation by UCB in the highly sensitive neuronal SH-SY5Y cells and in the resistant astrocytoma U87 cells. Upon treatment with a toxic dose of UCB, the conversion of LC3-I to LC3-II was detected in both cell lines. Inhibition of autophagy by E64d before UCB treatment increased SH-SY5Y cell mortality and made U87 cells sensitive to UCB. In SH-SY5Y autophagy related genes ATG8 (5 folds), ATG18 (5 folds), p62 (3 folds) and FAM 129A (4.5 folds) were induced 8h after UCB treatment while DDIT4 upregulation (13 folds) started at 4h. mTORC1 inactivation by UCB was confirmed by phosphorylation of 4EBP1. UCB induced LC3-II conversion was completely prevented by pretreating cells with the calcium chelator BAPTA and reduced by 65% using the ER-stress inhibitor 4-PBA. Pretreatment with the PKC inhibitor reduced LC3 mRNA by 70% as compared to cells exposed to UCB alone. Finally, autophagy induction by Trifluoroperazine (TFP) increased the cell viability of rat hippocampal primary neurons upon UCB treatment from 60% to 80%. In SH-SY5Y cells, TFP pretreatment blocked the UCB-induced cleaved caspase-3 protein expression, decreased LDH release from 50% to 23%, reduced the UCB-induction of HO1, CHOP and IL-8 mRNAs by 85%, 70% and 97%. Collectively these data indicate that the activation of autophagy protects neuronal cells from UCB cytotoxicity. The mechanisms of autophagy activation by UCB involves mTOR/ER-stress/PKC/calcium signaling. Copyright © 2017 Elsevier B.V. All rights reserved.

Effects of haemolysis, urea and bilirubin on the precision of digoxin and insulin radioimmunoassays

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Dwenger, A.; Trautschold, I.

1982-01-01

The influence of haemolysis, uraemia and hyperbilirubinaemia on the radioimmunoassay for both digoxin and insulin has been investigated for five separation techniques (dextran/charcoal; coated tube; polyethyleneglycol 4000; sodium sulphite; double antibody). Recoveries, and intra- and interassay precision were calculated. It was demonstrated that even in serum samples with a rather high degree of haemolysis (haemoglobin up to 50 g/l) digoxin can be measured by using each of the five separation techniques without any significant interference. Visible haemolysis (haemoglobin above 200 mg/l) leads either to disturbance or to a complete failure of insulin radioimmunoassays with all separation techniques. This effect can be largely neutralized, and precision improved, by using N-ethyl-maleimide. With the exception of the coated tube separation technique the intraassay precision has a CV of < 10%, and the interassay CV is between 10 and 20%. Elevated urea concentrations interfered in the digoxin radioimmuno-assay only when the coated tube technique was used. The insulin radioimmunoassay, however was affected by high urea when either the double antibody or the coated tube technique was used. Here the intraassay precision also has a coefficient of variation < 10%, the interassay CV lying between 10 and 20%. Bilirubin influenced the digoxin test when the sodium sulphite separation was used, and it affected the insulin determinations with polyethyleneglycol 4000 and sodium sulphite. The intra- and interassay precision were however also around 10% and between 10 and 20% respectively. Compared with the interassay precision of 15% CV for digoxin and 13% for insulin for a pool-serum from blood donors, the decrease of interassay precision caused by haemolysis, uraemia and hyperbilirubin-aemia was insignificant.

Plasma exchange combining with plasma bilirubin adsorption effectively removes toxic substances and improves liver functions of hepatic failure patients.

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Che, X-Q; Li, Z-Q; Chen, Z; Guo, D; Jia, Q-Y; Jiang, S-C; Cai, J

2018-02-01

Hepatic failure (HF) is a kind of complex disease characterizing with liver dysfunction and a few clinical complications. Artificial liver support system (ALSS) has been applied to HF patients to improve dysfunctional liver in recent years. This study aims to evaluate therapeutic effects of ALSS approaches, including plasma exchange (PE), plasma diafiltration (PDF) and plasma bilirubin adsorption (PBA), on liver function of HF patients. This study is a retrospective analysis involving 516 patients diagnosed as HF between February 2014 and February 2015. Patients were randomly divided into PE, PDF, PE plus PBA, and PDF plus PBA group. Meanwhile, single-drug group and combined-drug group were also divided. The liver functions, capability of removing toxic substances and coagulation functions were evaluated both pre-treatment and post-treatment. The side effects and hospital improvement rate were also observed post-treatment. Hospital improvement rate achieves to 69.6%. TBIL levels and MELD scores were significantly decreased post-treatment compared to pre-treatment (phigher compared to PE and PDF group (p=0.002, 0.002, respectively). MELD scores were significantly decreased post-treatment compared to pre-treatment in each group (pbetter role in removing toxic substances, improving liver functions of HF patients.

A decrease in total bilirubin predicted hyper-LDL cholesterolemia in a health screening population.

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Oda, Eiji

2014-08-01

To investigate cross-sectional and longitudinal associations between serum total bilirubin (TB) and LDL cholesterol. It is a retrospective observational study. Cross-sectional and longitudinal associations between TB and hyper-LDL cholesterolemia were investigated in a health screening population. Odds ratios (ORs) of coexisting hyper-LDL cholesterolemia for TB were calculated in 3,866 subjects, Spearman's correlation coefficients between baseline TB and LDL cholesterol at baseline and after 4 years were calculated in 1,735 subjects who did not use antihyperlipidemic drugs and hazard ratios (HRs) of incident hyper-LDL cholesterolemia for TB were calculated in 1,992 followed subjects. The ORs (p values) of coexisting hyper-LDL cholesterolemia for each 1 SD increase in TB was 1.04 (0.998) adjusted for sex, age, smoking, LDL cholesterol and other confounders. Spearman's correlation coefficients (p values) between baseline TB and LDL cholesterol at baseline and after 4 years and changes in LDL cholesterol were -0.026 (0.271), -0.078 (0.001) and -0.062 (0.010), respectively. Among 1,992 followed subjects, 481 developed hyper-LDL cholesterolemia during 4 years (60.4 per 1,000 person-years). The HRs (95% confidence intervals; p values) of incident hyper-LDL cholesterolemia for each 1 SD increase in TB was 0.86 (0.77-0.96; 0.006) adjusted for sex, age, smoking, LDL cholesterol, body mass index, triglycerides, HDL cholesterol, fasting glucose and other confounders. The quintiles of TB were significantly associated with the incident hyper-LDL cholesterolemia adjusted for the above covariates (p for trend = 0.008). A decrease in TB predicted incident hyper-LDL cholesterolemia in a health screening population. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Bilirubin oxidase-like proteins from Podospora anserina: promising thermostable enzymes for application in transformation of plant biomass.

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Xie, Ning; Ruprich-Robert, Gwenaël; Silar, Philippe; Chapeland-Leclerc, Florence

2015-03-01

Plant biomass degradation by fungi is a critical step for production of biofuels, and laccases are common ligninolytic enzymes envisioned for ligninolysis. Bilirubin oxidases (BODs)-like are related to laccases, but their roles during lignocellulose degradation have not yet been fully investigated. The two BODs of the ascomycete fungus Podospora anserina were characterized by targeted gene deletions. Enzymatic assay revealed that the bod1(Δ) and bod2(Δ) mutants lost partly a thermostable laccase activity. A triple mutant inactivated for bod1, bod2 and mco, a previously investigated multicopper oxidase gene distantly related to laccases, had no thermostable laccase activity. The pattern of fruiting body production in the bod1(Δ) bod2(Δ) double mutant was changed. The bod1(Δ) and bod2(Δ) mutants were reduced in their ability to grow on ligneous and cellulosic materials. Furthermore, bod1(Δ) and bod2(Δ) mutants were defective towards resistance to phenolic substrates and H2 O2 , which may also impact lignocellulose breakdown. Double and triple mutants were more affected than single mutants, evidencing redundancy of function among BODs and mco. Overall, the data show that bod1, bod2 and mco code for non-canonical thermostable laccases that participate in the degradation of lignocellulose. Thanks to their thermal stability, these enzymes may be more promising candidate for biotechnological application than canonical laccases. © 2014 Society for Applied Microbiology and John Wiley & Sons Ltd.

Astrocyte reactivity to unconjugated bilirubin requires TNF-α and IL-1β receptor signaling pathways.

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Fernandes, Adelaide; Barateiro, Andreia; Falcão, Ana Sofia; Silva, Sandra Leit-Ao; Vaz, Ana Rita; Brito, Maria Alexandra; Silva, Rui Fernando Marques; Brites, Dora

2011-01-01

Jaundice and sepsis are common neonatal conditions that can lead to neurodevelopment sequelae, namely if present at the same time. We have reported that tumor necrosis factor (TNF)-α and interleukin (IL)-1β are produced by cultured neurons and mainly by glial cells exposed to unconjugated bilirubin (UCB). The effects of these cytokines are mediated by cell surface receptors through a nuclear factor (NF)-κB-dependent pathway that we have showed to be activated by UCB. The present study was designed to evaluate the role of TNF-α and IL-1β signaling on astrocyte reactivity to UCB in rat cortical astrocytes. Exposure of astrocytes to UCB increased the expression of both TNF-α receptor (TNFR)1 and IL-1β receptor (IL-1R)1, but not TNFR2, as well as their activation, observed by augmented binding of receptors' molecular adaptors, TRAF2 and TRAF6, respectively. Silencing of TNFR1, using siRNA technology, or blockade of IL-1β cascade, using its endogenous antagonist, IL-1 receptor antagonist (IL-1ra), prevented UCB-induced cytokine release and NF-κB activation. Interestingly, lack of TNF-α signal transduction reduced UCB-induced cell death for short periods of incubation, although an increase was observed after extended exposure; in contrast, inhibition of IL-1β cascade produced a sustained blockade of astrocyte injury by UCB. Together, our data show that inflammatory pathways are activated during in vitro exposure of rat cortical astrocytes to UCB and that this activation is prolonged in time. This supports the concept that inflammatory pathways play a role in brain damage by UCB, and that they may represent important pharmacological targets. Copyright © 2010 Wiley-Liss, Inc.

Spectrofluorimetric quantification of bilirubin using yttrium-norfloxacin complex as a fluorescence probe in serum samples

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Kamruzzaman, Mohammad; Alam, Al-Mahmnur [Department of Chemistry, Kyungpook National University, Daegu 702-701 (Korea, Republic of); Hak Lee, Sang, E-mail: shlee@knu.ac.kr [Department of Chemistry, Kyungpook National University, Daegu 702-701 (Korea, Republic of); Ho Kim, Young, E-mail: youngkim@knu.ac.kr [Research Institute of Advanced Energy Technology, Kyungpook National University, Daegu 702-701 (Korea, Republic of); Kim, Gyu-Man [School of Mechanical Engineering, Kyungpook National University, Daegu 702-701 (Korea, Republic of); Hyub Oh, Sang [Center for Gas Analysis, Korea Research Institute of Standards and Science, Daejeon 305-600 (Korea, Republic of)

2012-11-15

A simple and sensitive spectrofluorimetric method was developed to determine trace amounts of bilirubin (BR) using yttrium (Y{sup 3+})-norfloxacin (NFLX) complex as a fluorescence (FL) probe. NFLX can form a stable binary complex with Y{sup 3+} and markedly enhances the weak FL signal of the NFLX. The FL intensity of the Y{sup 3+}-NFLX complex decreased significantly in the presence of BR in a buffer solution at pH=7.2. Under optimal conditions, the FL intensity decreased according to the BR concentration and showed a good linear relationship in the range of 0.03-2.3 {mu}g mL{sup -1} of BR with a correlation coefficient of 0.9988. The limit of detection for the determination of BR was 2.8 ng mL{sup -1} with a relative standard deviation (RSD) of 1.55% for five replicate determination of 0.05 {mu}g mL{sup -1} BR. The presented method offers higher sensitivity with simple instrumentation and was applied successfully in detecting BR at low concentrations. Highlights: Black-Right-Pointing-Pointer Weak FL signal of NFLX was enhanced at 419 nm by forming binary complex with Y{sup 3+}. Black-Right-Pointing-Pointer The FL intensity of Y{sup 3+}-NFLX complex was quenched markedly in the presence of ATP. Black-Right-Pointing-Pointer NFLX can transfer energy to Y{sup 3+} and BR and form the Y{sup 3+}-NFLX-ATP ternary complex. Black-Right-Pointing-Pointer The reduced FL intensity of the system was correlated with the concentration of BR. Black-Right-Pointing-Pointer The method is applied to determine BR at low concentration (2.8 ng mL{sup -1}) in serum.

Evaluation of treatment thresholds for unconjugated hyperbilirubinemia in preterm infants: effects on serum bilirubin and on hearing loss?

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Christian V Hulzebos

Full Text Available BACKGROUND: Severe unconjugated hyperbilirubinemia may cause deafness. In the Netherlands, 25% lower total serum bilirubin (TSB treatment thresholds were recently implemented for preterm infants. OBJECTIVE: To determine the rate of hearing loss in jaundiced preterms treated at high or at low TSB thresholds. DESIGN/METHODS: In this retrospective study conducted at two neonatal intensive care units in the Netherlands, we included preterms (gestational age 35 dB. RESULTS: There were 479 patients in the high and 144 in the low threshold group. Both groups had similar gestational ages (29.5 weeks and birth weights (1300 g. Mean and mean peak TSB levels were significantly lower after the implementation of the novel thresholds: 152 ± 43 µmol/L and 212 ± 52 µmol/L versus 131 ± 37 µmol/L and 188 ± 46 µmol/L for the high versus low thresholds, respectively (P<0.001. The incidence of hearing loss was 2.7% (13/479 in the high and 0.7% (1/144 in the low TSB threshold group (NNT = 50, 95% CI, 25-3302. CONCLUSIONS: Implementation of lower treatment thresholds resulted in reduced mean and peak TSB levels. The incidence of hearing impairment in preterms with a gestational age <32 weeks treated at low TSB thresholds was substantially lower compared to preterms treated at high TSB thresholds. Further research with larger sample sizes and power is needed to determine if this effect is statistically significant.

Effect of Probiotics on Serum Bilirubin Level in Term Neonates with Jaundice; A Randomized Clinical Trial

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Yadollah Zahed Pasha

2017-10-01

Full Text Available Background In recent years, tendency to use drugs has been increasing in the treatment of neonatal jaundice. Several drugs have been used since then, but the effect of probiotics on serum bilirubin level (SBL is not so clear. This study was conducted to evaluate the effect of probiotics on SBL and the duration of phototherapy in term neonates with hyperbilirubinemia. Materials and Methods: In this randomized clinical trial, we studied 150 term neonate with jaundice hospitalized for phototherapy in Amirkola Children’s Hospital, Babol- Iran, during October 5, 2016 till May 19, 2017. Eligible neonates were randomly divided into two; intervention (n=75, and control (n=75 groups. Both groups received standard conventional phototherapy, but the intervention group received 10 drop/day of probiotics (Pedilact Zisttakhmir. Co. Iran, until hospital discharge. The outcome variables were SBL and the duration of phototherapy. The data was analyzed by SPSS 22.0 and   the P 0.05.After 24, 48 and 72hours it decreased to 13.73±1.72, 10.92±1.87 and 10.25±1.32 in the intervention and 13.66±1.91, 11.01±1.69 and10.09 ±1.38 in the control groups, respectively but comparison of the amount of SBL reduction  between the two groups was not significant (P>0.05. The duration of phototherapy in the intervention group and the control group was 3.61±1.17 days and 3.72±1.18 days respectively (P>0.05. Conclusion Oral probiotics in neonates with jaundice has no significant effect on SBL and the duration of phototherapy. Further studies are needed to with longer time follow-up.

Elevated serum urate is a potential factor in reduction of total bilirubin: a Mendelian randomization study

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Zhang, Hui; Liu, Jing; Dong, Zheng; Ding, Yue; Qian, Qiaoxia; Zhou, Jingru; Ma, Yanyun; Mei, Zhendong; Chen, Xiangxiang; Li, Yuan; Yuan, Ziyu; Zhang, Juan; Yang, Yajun; Chen, Xingdong; Jin, Li; Zou, Hejian; Wang, Xiaofeng; Wang, Jiucun

2017-01-01

Aim A Mendelian randomization study (MRS) can be linked to a “natural” randomized controlled trial in order to avoid potential bias of observational epidemiology. We aimed to study the possible association between serum urate (SU) and total bilirubin (TBIL) using MRS. Materials and Methods An observational epidemiological study using ordinary least squares (OLS) regression and MRS using two-stage least square (TLS) regression was conducted to assess the effect of SU on TBIL. The comparison between the OLS regression and the TLS regression was analyzed by the Durbin-Hausman test. If the p value is significant, it suggests that the OLS regression cannot evaluate the relationship between exposure and outcome, and the TLS regression is precise; while if the p value is not significant, there would be no significant difference between the two regressions. Results A total of 3,753 subjects were analyzed. In OLS regression, there was no significant association between SU and TBIL in all subjects and subgroup analysis (all p > 0.05). However, MRS revealed a negative correlation between SU and TBIL after adjustment for confounders (beta = –0.021, p = 0.010). Further analysis was conducted in different SU subgroups, and results show that elevated SU was associated with a significant reduction in TBIL after adjustment for hyperuricemic subjects (beta = –0.053, p = 0.027). In addition, the results using the Durbin-Hausman test further confirmed a negative effect of SU on TBIL (p = 0.002 and 0.010, respectively). Conclusions This research shows for the first time that elevated SU was a potential causal factor in the reduction of TBIL and it provides strong evidence to resolve the controversial association between SU and TBIL. PMID:29262606

Biofuel cells based on direct enzyme-electrode contacts using PQQ-dependent glucose dehydrogenase/bilirubin oxidase and modified carbon nanotube materials.

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Scherbahn, V; Putze, M T; Dietzel, B; Heinlein, T; Schneider, J J; Lisdat, F

2014-11-15

Two types of carbon nanotube electrodes (1) buckypaper (BP) and (2) vertically aligned carbon nanotubes (vaCNT) have been used for elaboration of glucose/O2 enzymatic fuel cells exploiting direct electron transfer. For the anode pyrroloquinoline quinone dependent glucose dehydrogenase ((PQQ)GDH) has been immobilized on [poly(3-aminobenzoic acid-co-2-methoxyaniline-5-sulfonic acid), PABMSA]-modified electrodes. For the cathode bilirubin oxidase (BOD) has been immobilized on PQQ-modified electrodes. PABMSA and PQQ act as promoter for enzyme bioelectrocatalysis. The voltammetric characterization of each electrode shows current densities in the range of 0.7-1.3 mA/cm(2). The BP-based fuel cell exhibits maximal power density of about 107 µW/cm(2) (at 490 mV). The vaCNT-based fuel cell achieves a maximal power density of 122 µW/cm(2) (at 540 mV). Even after three days and several runs of load a power density over 110 µW/cm(2) is retained with the second system (10mM glucose). Due to a better power exhibition and an enhanced stability of the vaCNT-based fuel cells they have been studied in human serum samples and a maximal power density of 41 µW/cm(2) (390 mV) can be achieved. Copyright © 2014 Elsevier B.V. All rights reserved.

Exposure to lipopolysaccharide and/or unconjugated bilirubin impair the integrity and function of brain microvascular endothelial cells.

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Filipa L Cardoso

Full Text Available BACKGROUND: Sepsis and jaundice are common conditions in newborns that can lead to brain damage. Though lipopolysaccharide (LPS is known to alter the integrity of the blood-brain barrier (BBB, little is known on the effects of unconjugated bilirubin (UCB and even less on the joint effects of UCB and LPS on brain microvascular endothelial cells (BMEC. METHODOLOGY/PRINCIPAL FINDINGS: Monolayers of primary rat BMEC were treated with 1 µg/ml LPS and/or 50 µM UCB, in the presence of 100 µM human serum albumin, for 4 or 24 h. Co-cultures of BMEC with astroglial cells, a more complex BBB model, were used in selected experiments. LPS led to apoptosis and UCB induced both apoptotic and necrotic-like cell death. LPS and UCB led to inhibition of P-glycoprotein and activation of matrix metalloproteinases-2 and -9 in mono-cultures. Transmission electron microscopy evidenced apoptotic bodies, as well as damaged mitochondria and rough endoplasmic reticulum in BMEC by either insult. Shorter cell contacts and increased caveolae-like invaginations were noticeable in LPS-treated cells and loss of intercellular junctions was observed upon treatment with UCB. Both compounds triggered impairment of endothelial permeability and transendothelial electrical resistance both in mono- and co-cultures. The functional changes were confirmed by alterations in immunostaining for junctional proteins β-catenin, ZO-1 and claudin-5. Enlargement of intercellular spaces, and redistribution of junctional proteins were found in BMEC after exposure to LPS and UCB. CONCLUSIONS: LPS and/or UCB exert direct toxic effects on BMEC, with distinct temporal profiles and mechanisms of action. Therefore, the impairment of brain endothelial integrity upon exposure to these neurotoxins may favor their access to the brain, thus increasing the risk of injury and requiring adequate clinical management of sepsis and jaundice in the neonatal period.

Influence of bilirubin, alcohol and certain drugs on the kinetics of sup(99m)Tc-diethyl IDA (EHIDA) in humans

Energy Technology Data Exchange (ETDEWEB)

Coenegracht, J.M.; Oei, T.L.; van Breda Vriesman, P.J.C.

1983-04-01

On the basis of the mathematical analysis of sup(99m)Tc-EHIDA hepatobiliary time-activity curves of normal individuals two rate constants, one related to accumulation of radioactivity (uptake) and the other to excretion, were calculated indicating a two-compartmental model. By means of computerized fitting the rate constant of excretion (Ksub(b)), the time of maximum uptake (Tsub(max)) and the rate constant of uptake (Ksub(a)) were calculated. In severely jaundiced patients (serum bilirubin concentrations >140 ..mu..mol/l) a markedly decreased or absent uptake of sup(99m)Tc-EHIDA was observed. In moderately jaundiced patients a low Ksub(b) was invariably observed; in obstructive jaundice due to malignant disease - but not in jaundice of benign obstructive or hepatocellular origin - an increase in Ksub(a) was frequently present. This latter finding was not always present, however, and consequently kinetic studies do not unequivocally differentiate between jaundice of obstructive and hepatocellular origin. A markedly increased uptake (a high Ksub(a)) was noticed in alcoholics and patients taking phenobarbital and diphenylhydantoin possibly because of drug-induced membrane alterations. When the alcoholics developed hepatocellular injury the Ksub(a) converted to normal values. Thus, sup(99m)Tc-EHIDA kinetics may be useful in the follow-up of patients with established or suspected alcoholism by virtue of the fact that it appears to be a sensitive monitor of functional changes in hepatocyte plasma membrane properties.

Validation of transcutaneous bilirubin nomogram for identifying neonatal hyperbilirubinemia in healthy Chinese term and late-preterm infants: a multicenter study

Directory of Open Access Journals (Sweden)

Zhangbin Yu

2014-06-01

Full Text Available OBJECTIVE: to prospectively validate a previously constructed transcutaneous bilirubin (TcB nomogram for identifying severe hyperbilirubinemia in healthy Chinese term and late-preterm infants. METHODS: this was a multicenter study that included 9,174 healthy term and late-preterm infants in eight hospitals of China. TcB measurements were performed using a JM-103 bilirubinometer. TcB values were plotted on a previously developed TcB nomogram, to identify the predictive ability for subsequent significant hyperbilirubinemia. RESULTS: in the present study, 972 neonates (10.6% developed significant hyperbilirubinemia. The 40th percentile of the nomogram could identify all neonates who were at risk of significant hyperbilirubinemia, but with a low positive predictive value (PPV (18.9%. Of the 453 neonates above the 95th percentile, 275 subsequently developed significant hyperbilirubinemia, with a high PPV (60.7%, but with low sensitivity (28.3%. The 75th percentile was highly specific (81.9% and moderately sensitive (79.8%. The area under the curve (AUC for the TcB nomogram was 0.875. CONCLUSIONS: this study validated the previously developed TcB nomogram, which could be used to predict subsequent significant hyperbilirubinemia in healthy Chinese term and late-preterm infants. However, combining TcB nomogram and clinical risk factors could improve the predictive accuracy for severe hyperbilirubinemia, which was not assessed in the study. Further studies are necessary to confirm this combination.

Validation of transcutaneous bilirubin nomogram for identifying neonatal hyperbilirubinemia in healthy Chinese term and late-preterm infants: a multicenter study.

Science.gov (United States)

Yu, Zhangbin; Han, Shuping; Wu, Jinxia; Li, Mingxia; Wang, Huaiyan; Wang, Jimei; Liu, Jiebo; Pan, Xinnian; Yang, Jie; Chen, Chao

2014-01-01

to prospectively validate a previously constructed transcutaneous bilirubin (TcB) nomogram for identifying severe hyperbilirubinemia in healthy Chinese term and late-preterm infants. this was a multicenter study that included 9,174 healthy term and late-preterm infants in eight hospitals of China. TcB measurements were performed using a JM-103 bilirubinometer. TcB values were plotted on a previously developed TcB nomogram, to identify the predictive ability for subsequent significant hyperbilirubinemia. in the present study, 972 neonates (10.6%) developed significant hyperbilirubinemia. The 40(th) percentile of the nomogram could identify all neonates who were at risk of significant hyperbilirubinemia, but with a low positive predictive value (PPV) (18.9%). Of the 453 neonates above the 95(th) percentile, 275 subsequently developed significant hyperbilirubinemia, with a high PPV (60.7%), but with low sensitivity (28.3%). The 75(th) percentile was highly specific (81.9%) and moderately sensitive (79.8%). The area under the curve (AUC) for the TcB nomogram was 0.875. this study validated the previously developed TcB nomogram, which could be used to predict subsequent significant hyperbilirubinemia in healthy Chinese term and late-preterm infants. However, combining TcB nomogram and clinical risk factors could improve the predictive accuracy for severe hyperbilirubinemia, which was not assessed in the study. Further studies are necessary to confirm this combination. Copyright © 2014 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Changes in erythrocytic deformability and plasma viscosity in neonatal ictericia.

Science.gov (United States)

Bonillo-Perales, A; Muñoz-Hoyos, A; Martínez-Morales, A; Molina-Carballo, A; Uberos-Fernández, J; Puertas-Prieto, A

1999-01-01

We studied 45 full-term newborns divided into 3 groups. Group 1: 17 newborns with bilirubin ictericia (bilirubin 11-20 mg/dL) and Group 3: 10 newborns with moderate hemolytic ictericia needing exchange transfusion. The following were studied: erythrocytic deformability, plasma viscosity, plasmatic osmolarity, seric bilirubin, bilirubin/albumin ratio, free fatty acids and corpuscular volume of the erythrocytes. In full-term newborns, the following are risk factors for increased erythrocytic rigidity: neonatal hemolytic illness (p = 0.004, odds ratio: 7.02), increases in total bilirubin (p = 0.02, odds ratio: 4.3) and increases in the bilirubin/albumin ratio (p = 0.025, odds ratio: 4.25). Furthermore, the most important risk factor for high plasma viscosity is also neonatal hemolytic illness (p = 0.01, odds ratio: 2.30). The role of total bilirubin is also important (p = 0.09, odds ratio: 2.10), while that of the bilirubin/albumin ratio (p = 0.012, NS) is less so. The greater the hemolysis, the greater the erythrocytic rigidity and plasma viscosity (p ictericia, hemolytic illness and increases in the bilirubin/albumin ratio are accompanied by rheological alterations that could affect cerebral microcirculation and cause a neurological deficit not exclusively related to the levels of bilirubin in plasma.

Cytochrome P450 2A5 and bilirubin: Mechanisms of gene regulation and cytoprotection

Energy Technology Data Exchange (ETDEWEB)

Kim, Sangsoo Daniel; Antenos, Monica [Department of Biomedical Sciences, University of Guelph, Guelph, Ontario, N1G 2W1 (Canada); Squires, E. James [Department of Animal and Poultry Sciences, University of Guelph, Guelph, Ontario, N1G 2W1 (Canada); Kirby, Gordon M., E-mail: gkirby@uoguelph.ca [Department of Biomedical Sciences, University of Guelph, Guelph, Ontario, N1G 2W1 (Canada)

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

Update on phototherapy in jaundiced neonates

DEFF Research Database (Denmark)

Ebbesen, Finn; Hansen, Thor Willy Ruud; Maisels, M Jeffrey

2017-01-01

is the current treatment of choice. OBJECTIVE: To present an update on the most important issues involved in phototherapy for jaundiced infants. RESULTS: Light absorption by bilirubin in the skin transforms the native Z,Z-bilirubin to conformational photoisomers Z,E-bilirubin and E,Z-bilirubin and structural...

The influence of bilirubin, alcohol and certain drugs on the kinetics of sup(99m)Tc-diethyl IDA (EHIDA) in humans

International Nuclear Information System (INIS)

Coenegracht, J.M.; Oei, T.L.; Breda Vriesman, P.J.C. van; Rijksuniversiteit Limburg, Maastricht

1983-01-01

On the basis of the mathematical analysis of sup(99m)Tc-EHIDA hepatobiliary time-activity curves of normal individuals two rate constants, one related to accumulation of radioactivity (uptake) and the other to excretion, were calculated indicating a two-compartmental model. By means of computerized fitting the rate constant of excretion (Ksub(b)), the time of maximum uptake (Tsub(max)) and the rate constant of uptake (Ksub(a)) were calculated. In severely jaundiced patients (serum bilirubin concentrations >140 μmol/l) a markedly decreased or absent uptake of sup(99m)Tc-EHIDA was observed. In moderately jaundiced patients a low Ksub(b) was invariably observed; in obstructive jaundice due to malignant disease - but not in jaundice of benign obstructive or hepatocellular origin - an increase in Ksub(a) was frequently present. This latter finding was not always present, however, and consequently kinetic studies do not unequivocally differentiate between jaundice of obstructive and hepatocellular origin. A markedly increased uptake (a high Ksub(a)) was noticed in alcoholics and patients taking phenobarbital and diphenylhydantoin possibly because of drug-induced membrane alterations. When the alcoholics developed hepatocellular injury the Ksub(a) converted to normal values. Thus, sup(99m)Tc-EHIDA kinetics may be useful in the follow-up of patients with established or suspected alcoholism by virtue of the fact that it appears to be a sensitive monitor of functional changes in hepatocyte plasma membrane properties. (orig.)

Membraneless enzymatic ethanol/O2 fuel cell: Transitioning from an air-breathing Pt-based cathode to a bilirubin oxidase-based biocathode

Science.gov (United States)

Aquino Neto, Sidney; Milton, Ross D.; Hickey, David P.; De Andrade, Adalgisa R.; Minteer, Shelley D.

2016-08-01

The bioelectrooxidation of ethanol was investigated in a fully enzymatic membraneless ethanol/O2 biofuel cell assembly using hybrid bioanodes containing multi-walled carbon nanotube (MWCNT)-decorated gold metallic nanoparticles with either a pyrroloquinoline quinone (PQQ)-dependent alcohol dehydrogenase (ADH) enzyme or a nicotinamide adenine dinucleotide (NAD+)-dependent ADH enzyme. The biofuel cell anode was prepared with the PQQ-dependent enzyme and designed using either a direct electron transfer (DET) architecture or via a mediated electron transfer (MET) configuration through a redox polymer, 1,1‧-dimethylferrocene-modified linear polyethyleneimine (FcMe2-C3-LPEI). In the case of the bioanode containing the NAD+-dependent enzyme, only the mediated electron transfer mechanism was employed using an electropolymerized methylene green film to regenerate the NAD+ cofactor. Regardless of the enzyme being employed at the anode, a bilirubin oxidase-based biocathode prepared within a DET architecture afforded efficient electrocatalytic oxygen reduction in an ethanol/O2 biofuel cell. The power curves showed that DET-based bioanodes via the PQQ-dependent ADH still lack high current densities, whereas the MET architecture furnished maximum power density values as high as 226 ± 21 μW cm-2. Considering the complete membraneless enzymatic biofuel cell with the NAD+-dependent ADH-based bioanode, power densities as high as 111 ± 14 μW cm-2 were obtained. This shows the advantage of PQQ-dependent ADH for membraneless ethanol/O2 biofuel cell applications.

A Perspective on a Possible Relation Between the Psychopathology of the Schizophrenia/Schizoaffective Spectrum and Unconjugated Bilirubin: A Longitudinal Protocol Study.

Science.gov (United States)

Gama Marques, João; Arantes-Gonçalves, Filipe

2018-01-01

Some authors suggest a relation between Unconjugated Bilirubin (UCB) plasma high levels and schizophrenia, as schizophrenia patients have been showing higher UCB levels when compared with other psychiatric patients and general population. These higher UCB levels have been already correlated with acute psychotic states, positive symptoms, and poor outcome in patients with schizophrenia. Schizophrenia and schizoaffective disorders share common symptoms but there aren't yet accepted biomarkers for their distinction. In our study protocol we propose an observational longitudinal study on a sample composed of two subgroups: patients with schizophrenia and patients with schizoaffective disorder. We will compare the UCB levels between groups, and search for a possible correlation with patient's psychopathology. For that purpose we will use nosological, psychopathological, neuropsychological, and psychosocial instruments. Thus we will be testing two different hypotheses: (1) Is UCB serum level a diagnosis indicator, with categorical distinction potential, between groups of patients with different psychotic disorders? (2) Is UCB serum level a severity indicator, with dimensional distinction potential, among groups of patients with the same psychotic disorder? We believe that UCB mean levels may contribute to some clarification of this controversy, as a potential biological indicator, facilitating the distinction between these two diagnostic categories and\\or discriminating the dimensional severity among each of these psychotic conditions. Thus we may be opening a new opportunities for innovative and exciting biological psychiatry research regarding organic aspects in the schizophrenia spectrum.

Recent advances in the management of neonatal jaundice

Directory of Open Access Journals (Sweden)

Watchko JF

2014-11-01

Full Text Available Jon F Watchko Division of Newborn Medicine, Department of Pediatrics, University of Pittsburgh School of Medicine, Magee-Womens Research Institute, Pittsburgh, PA, USA Abstract: Advances in the clinical assessment strategies used to identify neonates at risk for the development of severe hyperbilirubinemia and bilirubin neurotoxicity, as well as the treatment measures to control hyperbilirubinemia in newborns, continue to be made. They include, among others, universal predischarge birth hospitalization bilirubin screening, the confirmation that hemolysis is an important risk factor for bilirubin neurotoxicity, the use of a numeric scoring system to help stage the severity of acute bilirubin encephalopathy, the potential advantages of turquoise-light phototherapy, and the potential role of heme-oxygenase inhibitors in preventing the need for exchange transfusions, all of which are reviewed here. Keywords: phototherapy, exchange transfusion, bilirubin, free bilirubin, bilirubin encephalopathy, kernicterus

Correlation between smoking and serum direct bilirubin level in male patients with coronary atherosclerotic heart disease%男性冠状动脉粥样硬化性心脏病患者吸烟与血清直接胆红素水平相关性分析

Institute of Scientific and Technical Information of China (English)

张艳艳; 贺建勋; 赵松; 袁慧; 王爱萍; 李志忠; 王苏

2016-01-01

Objective To analyze the correlation between smoking and serum direct bilirubin level in male patients with coronary atherosclerotic heart disease(CHD).Methods Totally 1 560 male patients with CHD from January 2009 to December 2012 in Beijing Anzhen Hospital,Capital Medical University were divided into 2 groups according to the median serum direct bilirubin level [2.890(0.010,9.960)μmol/L]:observation group (780 cases,serum direct bilirubin ≤ 2.890 μmol/L) and control group (780 cases,serum direct bilirubin ＞2.890.μmol/L).Age,body mass index,smoking,alcoho-drinking,hypertension history,diabetes history,acute myocardial infarction history,hemoglobin(Hb),white blood cell count(WBC),alanine aminotransferase(ALT),creatinine (Cr),uric acid (UC),total cholesterol (TC),triacylglycerol(TG),high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were analyzed.Results Age,Hb,Cr,UC and HDL-C in observation group were significantly lower than those in control group;smoking ratio,drinking ratio,TC,TG and LDL-C were significantly higher than those in control group [55 (32,80) years vs 57 (24,83) years,146(120,198) g/L vs 148 (120,187) g/L,81.0 (24.0,186.9) μmol/L vs 82.0 (45.0,197.0) μmol/L,348 (152,852) μmol/L vs 362 (132,741) μ mol/L,0.9 (0.4,2.1) mmol/L vs 0.9 (0.5,2.3) mmoL/L,68.7％ (536/780) vs 56.5％ (441/780),26.7％ (208/780) vs 21.7％ (169/780),4.3 (2.0,10.9) mmol/L vs4.0(2.1,9.1)mmol/L,1.74(0.27,16.71)mmol/L vs 1.45(0.05,18.29)mmol/L,2.7(1.0,8.5) mmol/L vs 2.5 (0.8,5.4) mmol/L] (P ＜ 0.05).Spearman rank correlation analysis showed a negative correlation between smoking and serum direct bilirubin level (r =-0.175,P ＜ 0.001).Multivariate logistic regression analysis revealed that smoking was an independent influence factor of serum direct bilirubin level (odds ratio =1.468,95％ confidence interval:1.170-1.842,P =0.001).Conclusion Smoking is correlated with low serum direct bilirubin level in male patients with CHD

The mechanisms of haem catabolism

International Nuclear Information System (INIS)

Brown, S.B.; King, R.F.G.J.

1978-01-01

The pathway of haem breakdown in living rats was studied by using 18 0 in the oxygen that the animals consumed. By cannulation of the common bile duct and collection of bile, labelled bilirubin was isolated and its mass spectrum determined. One set of results was obtained for a rat to which haemoglobin had been intravenously administered and another set obtained for a rat that was not given exogenous haem. Isomerization of bilirubin IXα to the XIIIα and IIIα isomers did not occur to any significant extent. The 18 O-labelling pattern obtained in the bilirubin was consistent with a Two-Molecule Mechanism, whereby the terminal lactam oxygen atoms of bilirubin are derived from different oxygen molecules. The consequences of this mechanism are discussed in terms of the possible intermediates of the catabolic pathway. 18 0-labelled bilirubin appeared in the bile in less than 10 min after exposure of the animals to labelled oxygen. This result suggests that all of the chemical transformations involving production of biliverdin, reduction to bilirubin and conjugation of the bilirubin are fast processes. The quantitative recovery of label obtained in the experiments suggests that there is little or no exchange of newly synthesized bilirubin with existing bilirubin pools in the animal. (author)

Review: Bilirubin pKa studies; new models and theories indicate high pKa values in water, dimethylformamide and DMSO

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Ostrow J

2010-03-01

Full Text Available Abstract Background Correct aqueous pKa values of unconjugated bilirubin (UCB, a poorly-soluble, unstable substance, are essential for understanding its functions. Our prior solvent partition studies, of unlabeled and [14C] UCB, indicated pKa values above 8.0. These high values were attributed to effects of internal H-bonding in UCB. Many earlier and subsequent studies have reported lower pKa values, some even below 5.0, which are often used to describe the behavior of UCB. We here review 18 published studies that assessed aqueous pKa values of UCB, critically evaluating their methodologies in relation to essential preconditions for valid pKa measurements (short-duration experiments with purified UCB below saturation and accounting for self-association of UCB. Results These re-assessments identified major deficiencies that invalidate the results of all but our partition studies. New theoretical modeling of UCB titrations shows remarkable, unexpected effects of self-association, yielding falsely low pKa estimates, and provides some rationalization of the titration anomalies. The titration behavior reported for a soluble thioether conjugate of UCB at high aqueous concentrations is shown to be highly anomalous. Theoretical re-interpretations of data in DMSO and dimethylformamide show that those indirectly-derived aqueous pKa values are unacceptable, and indicate new, high average pKa values for UCB in non-aqueous media (>11 in DMSO and, probably, >10 in dimethylformamide. Conclusions No reliable aqueous pKa values of UCB are available for comparison with our partition-derived results. A companion paper shows that only the high pKa values can explain the pH-dependence of UCB binding to phospholipids, cyclodextrins, and alkyl-glycoside and bile salt micelles.

Genetic disorders associated with neonatal jaundice

OpenAIRE

Morioka, Ichiro; Morikawa, Satoru; Yusoff, Surini; Harahap, Indra Sari Kusuma; Nishimura, Noriyuki; Yokoyama, Naoki; Matsuo, Masafumi; Rostenberghe, Hans Van; Nishio, Hisahide

2013-01-01

Abstract. Neonatal jaundice is very common in newborn infants. Although it is often a natural and transitional condition, some infants develop severe hyperbilirubinemia, in which unconjugated bilirubin in the serum may cross the blood-brain-barrier and cause bilirubin encephalopathy (acute bilirubin intoxication) or kernicterus (chronic bilirubin intoxication). To avoid these hazardous conditions, it is important to identify the infants at risk for developing severe hyperbilirubinemia. There ...

Risk factors of kernicterus; a study in 312 icteric neonates

OpenAIRE

Behjati Ardakani S; Nikkhah A; Sedaghat M

2007-01-01

Background: Kernicterus, also known as bilirubin encephalopathy, is a neurologic syndrome resulting from the deposition of unconjugated bilirubin in the basal ganglia and brainstem nuclei. Indirect bilirubin is toxic for brain. Neurologic dysfunction (BIND) that include acute phase (hyperbilirubin encephalopathy) and chronic phase (Kernicterus) resulting from hyperbilirubinemia and disruption of blood brain barrier. In this study, the association between bilirubin encephalopathy and risk fact...

High performance glucose/O2 compartment-less biofuel cell using DNA/CNTs as platform for immobilizing bilirubin oxidase as novel biocathode and integrated NH2-CNTs/dendrimer/glucose dehydrogenase/nile blue as bioanode

International Nuclear Information System (INIS)

Korani, Aazam; Salimi, Abdollah

2015-01-01

Highlights: • A biocathode based on immobilization of bilirubin oxidase onto MWCNTs/DNA is designed. • The performance of MWCNTs/DNA/BOD biocathode for O 2 reduction reaction is improved. • Compared to MWCNTs/BOD,at present biocathode current density to ORR increased 3 folds. • The onset potential for ORR is 0.57 V and its current density increased to 270 μA cm −2 . • A glucose/O 2 BFC with voltage of 0.66 V, J = 172 μAcm −2 and power of 45 μW cm −2 fabricated. - Abstract: Herein, deoxyribonucleic acid (DNA)/multi-walled carbon nanotube (MWCNTs) with enhanced negative charged density was used as a novel electrochemical platform for oriented immobilization of bilirubin oxidase. The proposed support improved the direct electron transfer kinetics of BOD and its catalytic activity toward oxygen reduction reaction (ORR). In comparison to BOD enzyme which immobilized directly onto MWCNTs the current density increased three folds and reached to 270 μA cm −2 at 0.405 V with an onset potential of 0.57 V (vs. Ag/AgCl). The ability of this modified electrode as a biocathode is investigated after assembling with bioanode. The bioanode prepared with covalent attachment of glucose dehydrogenase enzyme (GDH) and nile blue (NB) as an efficient mediator for coenzyme regeneration onto glassy carbon electrode modified with amino-carbon nanotubes(MWCNTs-NH 2 ) and carboxyl terminated polyamidoamin dendrimer (PAMAM-Den) as a multifunctional linker. Finally, the performance of one-compartment glucose/O 2 biofuel cell without separators is also investigated. The open circuit voltage of the cell and maximum current density are obtained 660 mV and 172 μA cm −2 , respectively, while the maximum power density of 45 μW cm −2 is achieved at 428 mV of the cell voltage in buffer solution saturated with O 2 and containing 50 mM of glucose. The stability of the constructed EBFC is investigated under continuous operation at maximum power. It is observed that the biofuel

Bili lights

Science.gov (United States)

... 3 things: Gestational age Bilirubin level in the blood Newborn's age (in hours) In severe cases of increased bilirubin, an exchange transfusion may be done instead. Alternative Names Phototherapy for jaundice; Bilirubin - bili lights; Neonatal ...

A product of heme catabolism modulates bacterial function and survival.

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Christopher L Nobles

Full Text Available Bilirubin is the terminal metabolite in heme catabolism in mammals. After deposition into bile, bilirubin is released in large quantities into the mammalian gastrointestinal (GI tract. We hypothesized that intestinal bilirubin may modulate the function of enteric bacteria. To test this hypothesis, we investigated the effect of bilirubin on two enteric pathogens; enterohemorrhagic E. coli (EHEC, a Gram-negative that causes life-threatening intestinal infections, and E. faecalis, a Gram-positive human commensal bacterium known to be an opportunistic pathogen with broad-spectrum antibiotic resistance. We demonstrate that bilirubin can protect EHEC from exogenous and host-generated reactive oxygen species (ROS through the absorption of free radicals. In contrast, E. faecalis was highly susceptible to bilirubin, which causes significant membrane disruption and uncoupling of respiratory metabolism in this bacterium. Interestingly, similar results were observed for other Gram-positive bacteria, including B. cereus and S. aureus. A model is proposed whereby bilirubin places distinct selective pressure on enteric bacteria, with Gram-negative bacteria being protected from ROS (positive outcome and Gram-positive bacteria being susceptible to membrane disruption (negative outcome. This work suggests bilirubin has differential but biologically relevant effects on bacteria and justifies additional efforts to determine the role of this neglected waste catabolite in disease processes, including animal models.

An albumin-fixed membrane for the removal of protein-bound toxins

International Nuclear Information System (INIS)

Ge Dongtao; Wu Dewang; Shi Wei; Ma Yuanyuan; Tian Xiangdong; Liang Pengfei; Zhang Qiqing

2006-01-01

Established methods for kidney dialysis do not work for liver failure because kidney dialysis removes only water-soluble toxins, while the liver normally removes albumin-bound toxins. In the present study, a polysulfone dialysis membrane with a -OH reactive group was prepared by hydrolyzing the chloromethylated polysulfone membrane, and the bovine serum albumin molecules were fixed into the membrane with 1,1'-carbonyldiimidazole activation. The content of albumin of the albumin-fixed membrane was 121.3 mg (g membrane) -1 . The albumin-fixed dialysis membranes were used to remove protein-bound toxins, bilirubin, from the bilirubin-albumin solution. The transfer rate of bilirubin of the albumin-fixed membrane was obviously higher compared to the normal dialysis membrane. The clearance of bilirubin with the albumin-fixed membrane was 49.8%. The albumin-fixed membrane can easily be regenerated by the bovine serum albumin and NaOH solution. Regeneration of the membrane suggested good mechanical and chemical stability, as well as good clearance of bilirubin. In addition, the effects of membrane thickness and bilirubin initial concentration on the removal of bilirubin were discussed

Metastable and equilibrium phase diagrams of unconjugated bilirubin IXα as functions of pH in model bile systems: Implications for pigment gallstone formation

Science.gov (United States)

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

The UGT1A1*28 allele and disease in childhood

DEFF Research Database (Denmark)

Petersen, Jesper Padkær

2014-01-01

Baggrund: Bilirubin er slutproduktet i hæms metabolisme. Ukonjugeret bilirubin er neuro-toksisk, men også en potent antioxidant af mulig klinisk relevans. Fortolkningen af observationelle bilirubin studier vanskeliggøres af potentiel revers kausalitet og adskillige tænkelige confoundere. En måde ...

The molecular basis of jaundice: An old symptom revisited.

Science.gov (United States)

Gazzin, Silvia; Masutti, Flora; Vitek, Libor; Tiribelli, Claudio

2017-08-01

Increased serum bilirubin level is a widely used diagnostic marker for hepatic illnesses. Nevertheless, mild elevation of unconjugated serum bilirubin (such as in Gilbert syndrome) has been recently demonstrated to correlate with low risk of chronic inflammatory and/or oxidative stress-mediated diseases. In accord, a low serum bilirubin level has emerged as an important predisposing factor or a biomarker of these pathologic conditions including cardiovascular, tumour, and possibly neurodegenerative diseases. Bilirubin possesses multiple biological actions with interaction in a complex network of enzymatic and signalling pathways. The fact that the liver is the main organ controlling the bioavailability of bilirubin emphasizes the central role of this organ in human health. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Metastable and equilibrium phase diagrams of unconjugated bilirubin IXα as functions of pH in model bile systems: Implications for pigment gallstone formation.

Science.gov (United States)

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. Copyright © 2015 the American Physiological Society.

Prediction of hyperbilirubinemia by noninvasive methods in full-term newborns

Directory of Open Access Journals (Sweden)

Danijela Furlan

2013-02-01

Full Text Available Introduction: The noninvasive screening methods for bilirubin determination were studied prospectively in a group of full-term healthy newborns with the aim of early prediction of pathological neonatal hyperbilirubinemia. Laboratory determination of bilirubin (Jendrassik-Grof (JG was compared to the noninvasive transcutaneous bilirubin (TcBIL together with the determination of bilirubin in cord blood.Methods: The study group consisted of 284 full-term healthy consecutively born infants in the period from March to June 2011. The whole group was divided into a group of physiological (n=199, and a group of pathological hyperbilirubinemia (n=85 according to the level of total bilirubin (220 μmol/L. Bilirubin in cord blood (CbBIL and from capillary blood at the age of three days was determined according to the JG, on the 3rd day TcBIL was also detected by Bilicheck bilirubinometer. The Kolmogorov-Smirnov and Mann-Whitney tests were used for the statistical analysis.Results: Bilirubin concentrations were statisti cally significantly different (CbBIL (p<0,001 on the 3rd day control sample (p<0,001, TcBil (p<0,001 between the groups of newborns with physiological (n=199 and pathological (n=85 hyperbilirubinemia. Using the cut-off value of cord blood bilirubin 28 μmol/L, we could predict the development of pathological hyperbiliru binemia with 98.8% prognostic specificity, and with 100% sensitivity that newborns will not require a phototherapy (all irradiated newborns were taken into account. We confirmed an excellent agreement between bilirubin concentrations determined by the TcBIL and JG methods for both groups of healthy full-term newborns.Conclusion: Based on our results, we could recommend that determination of the cord blood bilirubin in combination with the measurement of TcBIL should be implemented into practice for early prediction of pathological hyperbilirubinemia in full-term healthy newborns. The advantages of both methods in the routine

Effect of ultraviolet light on creatinine measurement in jaundiced specimens

International Nuclear Information System (INIS)

Nisbet, J.A.; D'Souza, R.

1986-01-01

During initial evaluation of a creatinine method using the RA-1000 analyser, experiments with addition of bilirubin indicated negligible interference. However the finding of a 'zero' creatinine value in an extremely jaundiced specimen prompted to re-examine the method. In contrast to earlier findings with normal plasma containing added bilirubin, the authors found that plasma from moderately or severely jaundiced patients gave creatinine values lower than those obtained with a reference method. Since bilirubin has been implicated in the interference, the authors studied the effect of destroying bilirubin with ultraviolet light to see if this provided a practical solution to the problem. (Auth.)

Estudo comparativo entre a medida plasmática e transcutânea de bilirrubina em recém-nascidos Factores asociados a la hipotermia durante transporte intrahospitalario en pacientes internados en una unidad de terapia intensiva neonatal Comparative study between plasma and transcutaneous bilirubin measurements in newborns

Directory of Open Access Journals (Sweden)

Patrícia Povaluk

2011-03-01

postnatal y presencia de factores de riesgo para hiperbilirrubinemia significativa. RESULTADOS: La asociación entre bilirrubina plasmática y transcutánea, en el momento de la indicación y después de 24 horas de fototerapia en las regiones frontal y esternal fue muy homogénea, debido a la fuerte correlación y los intervalos de confianza estrechos, tanto a 95% como a 99%. Se observó, además, respecto a la medida transcutánea en el área cubierta, 24 horas después del inicio de la fototerapia, la medida en el área esternal presentó correlación más fuerte con la plasmática (r=0,8599; p=0,0001. Las variables del RN analizadas no interfirieron significativamente en las medidas de bilirrubina. CONCLUSIÓN: Las dosificaciones transcutánea y plasmática presentan correlación fuerte antes de la fototerapia en las regiones frontal y esternal. Tras 24 horas de la fototerapia, la medida transcutánea esternal en área cubierta presentó mejor correlación.OBJECTIVE: To compare transcutaneous and plasma bilirubin measurements before and during phototerapy, on exposed and covered body areas, and to verify the association of the obtained levels with neonatal characteristics. METHODS: This cross-sectional study enrolled 44 newborn infants from April to October 2008. Simultaneous plasmatic and transcutaneous (frontal and sternal regions bilirubin assays were performed before and 24 hours after the beginning of phototerapy. On frontal and sternal regions, a small cover was placed and transcutaneous measurement was obtained from covered and exposed adjacent areas. The association between the measurements and neonatal weigh, sex, race, gestational and postnatal ages and risk factors for severe hyperbilirubinemia was calculated. RESULTS: There was a strong correlation between plasma and transcutaneous bilirubin assays measured in the frontal and sternal regions before the phototerapy, with narrow 95 and 99% confidence intervals. The covered sternal area presented the strongest

Hepatobiliary phase images using gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid-enhanced MRI as an imaging surrogate for the albumin–bilirubin grading system

Energy Technology Data Exchange (ETDEWEB)

Takatsu, Yasuo, E-mail: pcblue2@yahoo.co.jp [Department of Radiology, Osaka Red Cross Hospital, 5-30 Fudegasaki, Tennouji-ku, Osaka, 543-8555 (Japan); Division of Health Sciences, Graduate School of Medical Sciences, Kanazawa University, 5-11-80 Kodatsuno, Kanazawa, 920-0942 (Japan); Kobayashi, Satoshi, E-mail: satoshik@staff.kanazawa-u.ac.jp [Division of Health Sciences, Graduate School of Medical Sciences, Kanazawa University, 5-11-80 Kodatsuno, Kanazawa, 920-0942 (Japan); Miyati, Tosiaki, E-mail: ramiyati@mhs.mp.kanazawa-u.ac.jp [Division of Health Sciences, Graduate School of Medical Sciences, Kanazawa University, 5-11-80 Kodatsuno, Kanazawa, 920-0942 (Japan); Shiozaki, Toshiki, E-mail: shiozaki.toshiki@gmail.com [Department of Radiology, Osaka Red Cross Hospital, 5-30 Fudegasaki, Tennouji-ku, Osaka, 543-8555 (Japan)

2016-12-15

Objectives: To clarify the correlation between hepatobiliary phase (HBP) images using gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid (Gd-EOB-DTPA) and albumin–bilirubin (ALBI) grading system. Materials and methods: We evaluated 220 consecutive patients who underwent liver magnetic resonance imaging with Gd-EOB-DTPA. Quantitative liver–spleen contrast ratio (Q-LSC) was calculated in HBP images approximately 20 min after Gd-EOB-DTPA administration. To evaluate the degree of association between Q-LSC and ALBI grade, the Child–Pugh (C-P) score was used for comparison. Correlation coefficients were calculated, and median Q-LSC values were compared with the C-P scores and ALBI grades. The Steel–Dwass multiple comparison test was used for statistical analysis. Results: The correlation coefficient between Q-LSC and C-P score was −0.35, P < 0.0001, and the ALBI grade was −0.61, P < 0.0001. Q-LSC of overall median, C-P A, B, and C were 1.94, 1.91, 1.96, and 1.33, respectively. The differences between C-P A and C-P B, C-P B and C-P C, and C-P A and C-P C were P = 0.999, 0.126, and 0.149, respectively. Q-LSC of the overall median, ALBI grade 1, 2, and 3 were 1.94, 2.12, 1.69, and 1.30, respectively. The differences between ALBI grades 1 and 2, 2 and 3, and 1 and 3 were P < 0.0001, P = 0.0466, and P = 0.0035, respectively. Q-LSC was better correlated and discriminated by ALBI grade than C-P score. Conclusion: A strong correlation was observed between Q-LSC of an HBP image with Gd-EOB-DTPA and ALBI grade; HBP imaging could be a surrogate for the ALBI grade.

Newborn jaundice - discharge

Science.gov (United States)

... Biliary atresia Bili lights Bilirubin blood test Bilirubin encephalopathy Exchange transfusion Jaundice and breastfeeding Newborn jaundice Premature infant Rh incompatibility Patient Instructions Newborn ...

Cisplatin and gemcitabine in patients with advanced biliary tract cancer (ABC) and persistent jaundice despite optimal stenting: Effective intervention in patients with luminal disease.

Science.gov (United States)

Lamarca, Angela; Benafif, Sarah; Ross, Paul; Bridgewater, John; Valle, Juan W

2015-09-01

The advanced biliary tract cancer (ABC)-02 study established cisplatin and gemcitabine (CisGem) as a reference 1(st)-line regimen for patients with advanced/metastatic biliary tract cancer; patients with bilirubin ⩾ 1.5 × upper limit of normal (ULN) were excluded and there are few extant data for systemic treatment in the context of elevated bilirubin. Patients with ABC, receiving CisGem with a baseline bilirubin of ⩾ 1.5 × ULN were eligible for this retrospective analysis; response, toxicity and survival data were collected. Thirty-three patients of 545 screened; median age 59 years, range 23-79; 58% male, 58% with metastases (79% in the liver) of performance status (PS) 0 (33%), 1 (64%) or 2 (3%) were eligible. The median baseline bilirubin was 55 μmol/L (range 32-286); due to biliary tract obstruction (BTO, 76%) or liver metastases (LM, 24%). Toxicity was comparable to the ABC-02 study; bilirubin normalised in 64% during chemotherapy/follow-up. The median progression-free survival (PFS) was 6.9 months (95% confidence interval (CI): 4.4-9.0) and median overall survival (OS) 9.5 months (95% CI: 5.7-12.8). Patients with BTO had a longer PFS and OS than those with LM (7.0 versus 2.6 months; p = 0.1633 and 9.8 versus 4.4 months, hazard ratio (HR) 0.74; p = 0.465, respectively); not statistically significant (due to small sample size). Normalisation of bilirubin and completion of eight CisGem cycles were associated with longer OS (11.4 versus 2.9 months, HR 0.49; p = 0.08 and 15.2 versus 5.4 months, HR 0.12 p < 0.001, respectively). No difference in OS was shown between the bilirubin percentiles (for either PFS or OS). For PS 0-1 patients with ABC and high bilirubin due to luminal disease despite optimal stenting CisGem can be used safely with results similar to those in patients with normal bilirubin. Copyright © 2015 Elsevier Ltd. All rights reserved.

Bile pigments in pulmonary and vascular disease

Directory of Open Access Journals (Sweden)

Stefan W. Ryter

2012-03-01

Full Text Available The bile pigments, biliverdin and bilirubin, are endogenously-derived substances generated during enzymatic heme degradation. These compounds have been shown to act as chemical antioxidants in vitro. Bilirubin formed in tissues circulates in the serum, prior to undergoing hepatic conjugation and biliary excretion. The excess production of bilirubin has been associated with neurotoxicity, in particular to the newborn. Nevertheless, clinical evidence suggests that mild states of hyperbilirubinemia may be beneficial in protecting against cardiovascular disease in adults. Pharmacological application of either bilirubin and/or its biological precursor biliverdin, can provide therapeutic benefit in several animal models of cardiovascular and pulmonary disease. Furthermore, biliverdin and bilirubin can confer protection against ischemia/reperfusion injury and graft rejection secondary to organ transplantation in animal models. Several possible mechanisms for these effects have been proposed, including direct antioxidant and scavenging effects, and modulation of signaling pathways regulating inflammation, apoptosis, cell proliferation, and immune responses. The practicality and therapeutic-effectiveness of bile pigment application to humans remains unclear.

Effects of Zinc Deuteroporphyrin Bis Glycol on Newborn Mice After Heme-Loading

OpenAIRE

He, Cynthia X.; Campbell, Claire M.; Zhao, Hui; Kalish, Flora S.; Schulz, Stephanie; Vreman, Hendrik J.; Wong, Ronald J.; Stevenson, David K.

2011-01-01

Infants with hemolytic diseases frequently develop hyperbilirubinemia, but standard phototherapy only eliminates bilirubin after its production. A better strategy might be to directly inhibit heme oxygenase (HO), the rate-limiting enzyme in bilirubin production. Metalloporphyrins (Mps) are heme analogs that competitively inhibit HO activity in vitro and in vivo and suppress plasma bilirubin levels in vivo. A promising Mp, zinc deuteroporphyrin bis glycol (ZnBG), is orally absorbed and effecti...

Management of hyperbilirubinemia in near ... term newborns according to American Academy of Pediatrics Guidelines: Report of three cases

OpenAIRE

Naomi Esthemita Dewanto; Rinawati Rohsiswatmo

2009-01-01

All neonates have a transient rise in bilirubin levels, and about 30-50% of infants become visibly jaundiced.1,2 Most jaundice is benign; however, because of the potential brain toxicity of bilirubin, newborn infants must be monitored to identify those who might develop severe hyperbilirubinemia and, in rare cases, acute bilirubin encephalopathy or kernicterus. Ten percent of term infants and 25% of near-term infants have significant hyperbilirubinemia and requir...

Constitutional hepatic dysfunction (Gilbert's disease), about eleven cases studied in the Hospital Obrero de Lima

OpenAIRE

León Navarro, Oswaldo

2014-01-01

We report eleven cases of Constitutional Hepatic dysfunction (Gilbert's disease), studied at the Department of Gastroenterology of the Hospital Obrero de Lima. We place this disease in the group of non Chronicles Hemolytic jaundice due to congenital defects in bilirubin metabolism. It is noted, according to the new concepts of bilirubin metabolism, the pathogenic mechanism of this disease is related to deficient activity of glucuronyltransferase, the enzyme responsible for bilirubin conjugati...

3.3. Sorption activity of cross-linked polymers of ethynyl-piperidol

International Nuclear Information System (INIS)

Khalikov, D.Kh.

2012-01-01

The sorption activity of cross-linked polymers of ethynyl-piperidol was studied. The bilirubin sorption was studied as well. The kinetic of bilirubin sorption and human serum albumin at their joint presence in hydrogel solutions was defined. Bilirubin sorption and change of albumin composition was considered. The sorption of middle molecular peptides was considered as well. The sorption of endogenous toxin by means of ethynyl-piperidol polymers was done.

Gene replacement therapy for genetic hepatocellular jaundice.

Science.gov (United States)

van Dijk, Remco; Beuers, Ulrich; Bosma, Piter J

2015-06-01

Jaundice results from the systemic accumulation of bilirubin, the final product of the catabolism of haem. Inherited liver disorders of bilirubin metabolism and transport can result in reduced hepatic uptake, conjugation or biliary secretion of bilirubin. In patients with Rotor syndrome, bilirubin (re)uptake is impaired due to the deficiency of two basolateral/sinusoidal hepatocellular membrane proteins, organic anion-transporting polypeptide 1B1 (OATP1B1) and OATP1B3. Dubin-Johnson syndrome is caused by a defect in the ATP-dependent canalicular transporter, multidrug resistance-associated protein 2 (MRP2), which mediates the export of conjugated bilirubin into bile. Both disorders are benign and not progressive and are characterised by elevated serum levels of mainly conjugated bilirubin. Uridine diphospho-glucuronosyl transferase 1A1 (UGT1A1) is responsible for the glucuronidation of bilirubin; deficiency of this enzyme results in unconjugated hyperbilirubinaemia. Gilbert syndrome is the mild and benign form of inherited unconjugated hyperbilirubinaemia and is mostly caused by reduced promoter activity of the UGT1A1 gene. Crigler-Najjar syndrome is the severe inherited form of unconjugated hyperbilirubinaemia due to mutations in the UGT1A1 gene, which can cause kernicterus early in life and can be even lethal when left untreated. Due to major disadvantages of the current standard treatments for Crigler-Najjar syndrome, phototherapy and liver transplantation, new effective therapeutic strategies are under development. Here, we review the clinical features, pathophysiology and genetic background of these inherited disorders of bilirubin metabolism and transport. We also discuss the upcoming treatment option of viral gene therapy for genetic disorders such as Crigler-Najjar syndrome and the possible immunological consequences of this therapy.

A Comparison of Y-Type and T-Type Metallic Bilateral Biliary Stents in Patients with Malignant Hilar Biliary Obstruction

International Nuclear Information System (INIS)

Koh, Esther; Jin, Gong Yong; Hwang, Seung Bae; Choi, Eun Jung; Song, Ji Soo; Han, Young Min; Kwon, Keun Sang

2013-01-01

To compare the Y type (side-by-side) and T type (stent-in-stent) bilateral biliary metal stenting in malignant hilar obstruction in terms of treatment outcomes, including post-stenting serum bilirubin level and stent patency. 41 consecutive patients with advanced hilar malignancies who underwent percutaneous placement of bilateral metallic stents - Y (n = 23) and T types (n = 18) - were retrospectively reviewed. We evaluated stent patency after the procedure by cholangiogram and abdominal CT. Pre- and post-stenting serum bilirubin level (total, direct bilirubin) at 1 week and at 1 month were compared. Student t-test and Kaplan-Meier method were used in the statistical analysis. After comparing the median stent patency according to both types, they did not differ significantly (Y: 38 days, T: 61 days; p 0.141). There was a more decrease in the total and direct bilirubin of the T type compared to the Y type after 1 week (p = 0.013, 0.025). However, no significant difference existed between the decreasing bilirubin rates of both types after 1 month (p = 0.923, 0.742). In patients with malignant hilar obstruction, both Y and T type bilateral metallic biliary stents are effective methods. Stent patency and bilirubin decrease rates were not significantly different.

A Comparison of Y-Type and T-Type Metallic Bilateral Biliary Stents in Patients with Malignant Hilar Biliary Obstruction

Energy Technology Data Exchange (ETDEWEB)

Koh, Esther; Jin, Gong Yong; Hwang, Seung Bae; Choi, Eun Jung; Song, Ji Soo; Han, Young Min; Kwon, Keun Sang [Dept. of Chonbuk National University Hospital and Medical School, Jeonju (Korea, Republic of)

2013-04-15

To compare the Y type (side-by-side) and T type (stent-in-stent) bilateral biliary metal stenting in malignant hilar obstruction in terms of treatment outcomes, including post-stenting serum bilirubin level and stent patency. 41 consecutive patients with advanced hilar malignancies who underwent percutaneous placement of bilateral metallic stents - Y (n = 23) and T types (n = 18) - were retrospectively reviewed. We evaluated stent patency after the procedure by cholangiogram and abdominal CT. Pre- and post-stenting serum bilirubin level (total, direct bilirubin) at 1 week and at 1 month were compared. Student t-test and Kaplan-Meier method were used in the statistical analysis. After comparing the median stent patency according to both types, they did not differ significantly (Y: 38 days, T: 61 days; p 0.141). There was a more decrease in the total and direct bilirubin of the T type compared to the Y type after 1 week (p = 0.013, 0.025). However, no significant difference existed between the decreasing bilirubin rates of both types after 1 month (p = 0.923, 0.742). In patients with malignant hilar obstruction, both Y and T type bilateral metallic biliary stents are effective methods. Stent patency and bilirubin decrease rates were not significantly different.

Role of extrahepatic UDP-glucuronosyltransferase 1A1: Advances in understanding breast milk-induced neonatal hyperbilirubinemia

International Nuclear Information System (INIS)

Fujiwara, Ryoichi; Maruo, Yoshihiro; Chen, Shujuan; Tukey, Robert H.

2015-01-01

Newborns commonly develop physiological hyperbilirubinemia (also known as jaundice). With increased bilirubin levels being observed in breast-fed infants, breast-feeding has been recognized as a contributing factor for the development of neonatal hyperbilirubinemia. Bilirubin undergoes selective metabolism by UDP-glucuronosyltransferase (UGT) 1A1 and becomes a water soluble glucuronide. Although several factors such as gestational age, dehydration and weight loss, and increased enterohepatic circulation have been associated with breast milk-induced jaundice (BMJ), deficiency in UGT1A1 expression is a known cause of BMJ. It is currently believed that unconjugated bilirubin is metabolized mainly in the liver. However, recent findings support the concept that extrahepatic tissues, such as small intestine and skin, contribute to bilirubin glucuronidation during the neonatal period. We will review the recent advances made towards understanding biological and molecular events impacting BMJ, especially regarding the role of extrahepatic UGT1A1 expression. - Highlights: • Breast-feeding can be a factor for the development of neonatal hyperbilirubinemia. • UDP-glucuronosyltransferase (UGT) 1A1 is the sole bilirubin-metabolizing enzyme. • Extrahepatic UGT1A1 plays an important role in bilirubin metabolism. • We discuss the potential mechanism of breast milk-induced neonatal jaundice.

Role of extrahepatic UDP-glucuronosyltransferase 1A1: Advances in understanding breast milk-induced neonatal hyperbilirubinemia

Energy Technology Data Exchange (ETDEWEB)

Fujiwara, Ryoichi, E-mail: fujiwarar@pharm.kitasato-u.ac.jp [Department of Pharmaceutics, School of Pharmacy, Kitasato University, Tokyo (Japan); Maruo, Yoshihiro [Department of Pediatrics, Shiga University of Medical Science, Shiga (Japan); Chen, Shujuan [Department of Pharmacology, Laboratory of Environmental Toxicology, University of California at San Diego, La Jolla, CA 92093 (United States); Tukey, Robert H., E-mail: rtukey@ucsd.edu [Department of Pharmacology, Laboratory of Environmental Toxicology, University of California at San Diego, La Jolla, CA 92093 (United States); Department of Chemistry & Biochemistry, Laboratory of Environmental Toxicology, University of California at San Diego, La Jolla, CA 92093 (United States)

2015-11-15

Newborns commonly develop physiological hyperbilirubinemia (also known as jaundice). With increased bilirubin levels being observed in breast-fed infants, breast-feeding has been recognized as a contributing factor for the development of neonatal hyperbilirubinemia. Bilirubin undergoes selective metabolism by UDP-glucuronosyltransferase (UGT) 1A1 and becomes a water soluble glucuronide. Although several factors such as gestational age, dehydration and weight loss, and increased enterohepatic circulation have been associated with breast milk-induced jaundice (BMJ), deficiency in UGT1A1 expression is a known cause of BMJ. It is currently believed that unconjugated bilirubin is metabolized mainly in the liver. However, recent findings support the concept that extrahepatic tissues, such as small intestine and skin, contribute to bilirubin glucuronidation during the neonatal period. We will review the recent advances made towards understanding biological and molecular events impacting BMJ, especially regarding the role of extrahepatic UGT1A1 expression. - Highlights: • Breast-feeding can be a factor for the development of neonatal hyperbilirubinemia. • UDP-glucuronosyltransferase (UGT) 1A1 is the sole bilirubin-metabolizing enzyme. • Extrahepatic UGT1A1 plays an important role in bilirubin metabolism. • We discuss the potential mechanism of breast milk-induced neonatal jaundice.

The Influence of histamine H1-receptor on liver functions in immunized rabbits.

Science.gov (United States)

Tripathi, Trivendra; Shahid, Mohammad; Khan, Haris M; Khan, Rahat Ali; Siddiqui, Mashiatullah; Mahdi, Abbas Ali

2011-10-01

This study was designed to investigate the functional roles of histamine and histamine H1-receptor agonist and antagonist in the development of liver function impairment in immunized rabbits. The study comprised of six groups containing 18 rabbits each. Group III-VI received histamine (100 μg/kg, s.c.), H1R-agonist (HTMT, 10 μg/kg, s.c.), H1R-antagonist (pheniramine, 10 mg/kg, i.m.), and H1R-antagonist (pheniramine, 10 mg/kg, i.m.) plus histamine (100 μg/kg, s.c.), respectively, b.i.d. for 10 days. Group I (negative control) and group II (positive control) received sterile distilled water intramuscularly b.i.d. for 10 days. Groups II-VI were immunized on day 3 with intravenous injection of SRBC (1 × 10(9) cells/ml). Blood samples were collected on pre-immunization day 0, as well as on days 7-, 14-, 21-, 28-, and 58-post-immunization. Biochemical parameters AST, ALT, alkaline phosphatase and bilirubin [total bilirubin (TB), direct bilirubin (DB), and indirect bilirubin (IB)] were determined. On each experimental day, the mean values of serum enzymes and bilirubin in group I and group II showed no significant changes while in group III, IV, V, and VI, these enzymes and bilirubin levels showed significant changes (p pheniramine, and combination of histamine + pheniramine cause hepatic function impairment in terms of altered serum enzymes and bilirubin levels. The present findings suggest that HTMT causes moderate liver function impairment while others show mild impairment.

Clinical evaluation of Tc-99m-mebrofenin and comparison with Tc-disofenin for radionuclide hepatobiliary imaging

International Nuclear Information System (INIS)

Klingensmith, W. III; Fritzberg, A.; Spitzer, V.

1982-01-01

The clinical comparison reported indicates that Tc-mebrofenin has a significantly lower level of renal excretion that Tc-disofenin at all bilirubin levels. At a total bilirubin level of 25 mg/dl the renal excretion of Tc-mebrofenin is still less than the renal excretion of Tc-disofenin in subjects with normal bilirubin levels. In addition, renal radioactivity in images was never seen in subjects with normal bilirubins while visualization of renal radioactivity is routine in normal subjects with Tc-disofenin. No significant differences were found in any other parameter including hepatocyte extraction efficiency, time of maximum hepatic radioactivity, and hepatic parenchymal washout. This study indicates that Tc-mebrofenin is equal to Tc-disofenin in its hepatobiliary characteristics and superior in its renal characteristics

Neonatal jaundice

OpenAIRE

Evans, David

2007-01-01

About 50% of term and 80% of preterm babies develop jaundice, which usually appears 2-4 days after birth, and resolves spontaneously after 1-2 weeks. Jaundice is caused by bilirubin deposition in the skin. Most jaundice in newborn infants is a result of increased red cell breakdown and decreased bilirubin excretion.Breastfeeding, haemolysis, and some metabolic and genetic disorders also increase the risk of jaundice.Unconjugated bilirubin can be neurotoxic, causing an acute or chronic ence...

Neonatal jaundice: phototherapy

OpenAIRE

Woodgate, Paul; Jardine, Luke Anthony

2015-01-01

About 50% of term and 80% of preterm babies develop jaundice, which usually appears 2 to 4 days after birth, and resolves spontaneously after 1 to 2 weeks. Jaundice is caused by bilirubin deposition in the skin. Most jaundice in newborn infants is a result of increased red cell breakdown and decreased bilirubin excretion.Breastfeeding, haemolysis, and some metabolic and genetic disorders also increase the risk of jaundice.Unconjugated bilirubin can be neurotoxic, causing an acute or chroni...

Refractometric total protein concentrations in icteric serum from dogs.

Science.gov (United States)

Gupta, Aradhana; Stockham, Steven L

2014-01-01

To determine whether high serum bilirubin concentrations interfere with the measurement of serum total protein concentration by refractometry and to assess potential biases among refractometer measurements. Evaluation study. Sera from 2 healthy Greyhounds. Bilirubin was dissolved in 0.1M NaOH, and the resulting solution was mixed with sera from 2 dogs from which food had been withheld to achieve various bilirubin concentrations up to 40 mg/dL. Refractometric total protein concentrations were estimated with 3 clinical refractometers. A biochemical analyzer was used to measure biuret assay-based total protein and bilirubin concentrations with spectrophotometric assays. No interference with refractometric measurement of total protein concentrations was detected with bilirubin concentrations up to 41.5 mg/dL. Biases in refractometric total protein concentrations were detected and were related to the conversion of refractive index values to total protein concentrations. Hyperbilirubinemia did not interfere with the refractometric estimation of serum total protein concentration. The agreement among total protein concentrations estimated by 3 refractometers was dependent on the method of conversion of refractive index to total protein concentration and was independent of hyperbilirubinemia.

A dose-response model for the conventional phototherapy of the newborn.

Science.gov (United States)

Osaku, Nelson Ossamu; Lopes, Heitor Silvério

2006-06-01

Jaundice of the newborn is a common problem as a consequence of the rapid increment of blood bilirubin in the first days of live. In most cases, it is considered a physiological transient situation, but unmanaged hyperbilirubinemia can lead to death or serious injuries for the survivors. For decades, phototherapy has been used as the main method for prevention and treatment of hyperbilirubinaemia of the newborn. This work aims at finding a predictive model for the decrement of blood bilirubin for patients submitted to conventional phototherapy. Data from the phototherapy of 90 term newborns were collected and used in a multiple regression method. A rigorous statistical analysis was done in order to guarantee a correct and valid model. The obtained model was able to explain 78% of the variation of the dependent variable. We show that it is possible to predict the total serum bilirubin of the patient under conventional phototherapy by knowing its birth weight, bilirubin level at the beginning of treatment and the radiant energy density (dose). Besides, it is possible to infer the time necessary for a given decrement of bilirubin, under approximately constant irradiance. Statistical analysis of the obtained model shows that it is valid for several ranges of birth weight, initial bilirubin level, and radiant energy density. It is expected that the proposed model can be useful in the clinical management of hyperbilirubinemia of the newborn.

The Value of Bilicheck® as a Screening Tool for Neonatal Jaundice in the South of Iran

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Fariba Hemmati

2013-06-01

Full Text Available The gold standard to assess jaundice in neonates is the serum bilirubin measurement. Blood sampling for the determination of total serum bilirubin (TSB is painful for newborns and stressful for parents. The Bilicheck®, a new transcutaneous bilirubinometer, is considered as a more accurate measurement of bilirubin compared to the previous bilirubinometers courtesy of its advanced technology. The objective of this study was to evaluate the correlation between transcutaneous bilirubin (TcB measurements using the Bilicheck® device and TSB in some Iranian neonates and to determine the most reliable cut-off value with the highest sensitivity and desirable specificity for bilirubin measured by the Bilicheck® on the forehead. This prospective observational study was conducted in 2011 on 560 healthy neonates with jaundice. TcB was measured using the Bilicheck® (Respironic, USA within 30 minutes of TSB measurement via direct spectrophotometry. The results were assessed by simple linear regression analysis and receiver operative characteristic curve. There was good a correlation between TcB and TSB (r=0.969, r2=0.94, and this was not affected by sex, gestational age, postnatal age, and birth weight. TSB can be calculated through the measurement of TcB and use of the linear regression equation: TSB=-0.99+1.06TcB. Sensitivity and specificity of the Bilicheck® at the most reliable cut-off value (15 mg/dl were 96.6% and 99%, respectively. The findings of the present study indicate that the Bilicheck® is a non-invasive, simple, easy, and reliable method for bilirubin measurement in neonatal jaundice, especially in neonates with bilirubin levels ≤15 mg/dl.

Multi-wavelength spectrophotometric analysis for detection of xanthochromia in cerebrospinal fluid and accuracy for the diagnosis of subarachnoid hemorrhage.

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Smith, Andrew; Wu, Alan H B; Lynch, Kara L; Ko, Nerissa; Grenache, David G

2013-09-23

Cerebrospinal fluid (CSF) was examined for bilirubin, an important indicator for diagnosis of subarachnoid hemorrhage (SAH). A multi-wavelength (340, 415, and 460 nm) spectrophotometric assay was developed for the quantitative measurement of bilirubin in CSF, enabling the mathematical correction for absorbance of hemoglobin and proteins. Bilirubin and hemoglobin results were correlated to HPLC and a standard colorimetric assay, respectively. A subset of samples was sent for an absorbance reading at 450 nm following baseline correction. The multi-wavelength bilirubin assay was validated on 70 patients with confirmed SAH and 70 patients with neurologic symptoms who ruled out for SAH. The multi-wavelength spectrophometric assay demonstrated no interferences due to proteins (albumin) up to 30 g/l or oxyhemoglobin up to 260 mg/l. The assay limit of detection was 0.2 mg/l, linear to 20 mg/l, and CVs ranged from 1 to 6% at bilirubin concentrations of 0.84 and 2.1mg/l. The spectrophotometric assay correlated to HPLC and the colorimetric assay for bilirubin and hemoglobin, respectively. Results also correlated to the absorbance method (with removal of samples with high hemoglobin and proteins). The area under the ROC curve for diagnosis of SAH was 0.971 and 0.954 for the HPLC and spectrophotometric assay, respectively. At a cutoff of 0.2mg/l, the clinical specificity was 100% for both assays, and the clinical sensitivity was 94.3% and 88.6% for SAH for the HPLC and spectrophotometric asays, respectively. The multi-wavelength spectrophotometric assay is an objective alternative to visual inspection, HPLC, and absorbance for CSF bilirubin. Copyright © 2013 Elsevier B.V. All rights reserved.

Treated Neem Kernel Cake. *1A. Aruwayo, 2S.A

African Journals Online (AJOL)

The mean values for per cell volume (PCV), haemoglobin concentration ... protein, albumin, globulin, SGPT, total bilirubin and conjugated bilirubin in the .... Total proteins were estimated by the Biuret ... determined by Jaffe reaction (Sarre and.

Genetics Home Reference: Gilbert syndrome

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... instance because of dehydration, prolonged periods without food (fasting), illness, vigorous exercise, or menstruation. Some people with ... to conjugated bilirubin. Glucuronidation makes bilirubin dissolvable in water so that it can be removed from the ...

Hepatobiliary transporter expression and post-operative jaundice in patients undergoing partial hepatectomy.

Science.gov (United States)

Bernhardt, Gerwin A; Zollner, Gernot; Cerwenka, Herwig; Kornprat, Peter; Fickert, Peter; Bacher, Heinz; Werkgartner, Georg; Müller, Gabriele; Zatloukal, Kurt; Mischinger, Hans-Jörg; Trauner, Michael

2012-01-01

Post-operative hyperbilirubinaemia in patients undergoing liver resections is associated with high morbidity and mortality. Apart from different known factors responsible for the development of post-operative jaundice, little is known about the role of hepatobiliary transport systems in the pathogenesis of post-operative jaundice in humans after liver resection. Two liver tissue samples were taken from 14 patients undergoing liver resection before and after Pringle manoeuvre. Patients were retrospectively divided into two groups according to post-operative bilirubin serum levels. The two groups were analysed comparing the results of hepatobiliary transporter [Na-taurocholate cotransporter (NTCP); multidrug resistance gene/phospholipid export pump(MDR3); bile salt export pump (BSEP); canalicular bile salt export pump (MRP2)], heat shock protein 70 (HSP70) expression as well as the results of routinely taken post-operative liver chemistry tests. Patients with low post-operative bilirubin had lower levels of NTCP, MDR3 and BSEP mRNA compared to those with high bilirubin after Pringle manoeuvre. HSP70 levels were significantly higher after ischaemia-reperfusion (IR) injury in both groups resulting in 4.5-fold median increase. Baseline median mRNA expression of all four transporters prior to Pringle manoeuvre tended to be lower in the low bilirubin group whereas expression of HSP70 was higher in the low bilirubin group compared to the high bilirubin group. Higher mRNA levels of HSP70 in the low bilirubin group could indicate a possible protective effect of high HSP70 levels against IR injury. Although the exact role of hepatobiliary transport systems in the development of post-operative hyper bilirubinemia is not yet completely understood, this study provides new insights into the molecular aspects of post-operative jaundice after liver surgery. © 2011 John Wiley & Sons A/S.

Hemadsorption with Adult CytoSorb® in a Low Weight Pediatric Case

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Catalin Gabriel Cirstoveanu

2017-01-01

Full Text Available Cytokine adsorber (CytoSorb has been used successfully as adjunctive treatment for adult patients with elevated cytokine levels in the setting with severe sepsis and septic shock and to reduce blood myoglobin, unconjugated bilirubin, and conjugated bilirubin. In this article we present the case of a nine-month-old male infant who was admitted to the NICU due to sepsis after cardiac surgery, Fallot tetralogy, and multisystem organ failure (MSOF including liver failure and renal failure which was successfully treated by a combination of continuous hemodiafiltration (HDF and hemadsorption with CytoSorb. HDF was safe and effective from the first day for urea removal, but the patient’s bilirubin levels kept increasing gradually, culminating on the 9th day with a maximum value of 54 mg/dL of total bilirubin and 31.67 mg/dL of direct bilirubin when we performed hemadsorption with CytoSorb. Over the 49-hour period of hemadsorption, the total bilirubin value decreased from 54 to 14 mg/dL, and the patient’s general status improved considerably accompanied by a rapid drop of aminotransferases. Hemodynamic status has been improved as well and inotropes dropped rapidly. The patient’s ventilation settings improved during CytoSorb treatment permitting weaning the patient from mechanical ventilation after five days of hemadsorption. The patient was discharged home after 34 days of hospitalization, in a good general status.

Moderate Unconjugated Hyperbilirubinemia Causes a Transient but Delayed Suppression of Amplitude-Integrated Electroencephalographic Activity in Preterm Infants

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ter Horst, Hendrik J.; Bos, Arend F.; Duijvendijk, Jildou; Hulzebos, Christian V.

2012-01-01

Background: Unconjugated hyperbilirubinemia occurs frequently in preterm infants and may result in bilirubin encephalopathy. Amplitude-integrated electroencephalography (aEEG) is used to evaluate brain function in newborns. Objectives: To investigate the influence of total serum bilirubin (TSB) on

Mildly elevated serum total bilirubin is negatively associated with hemoglobin A1c independently of confounding factors among community-dwelling middle-aged and elderly persons

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Ryuichi Kawamoto

2017-08-01

Full Text Available Abnormally high glycated hemoglobin (Hb (HbA1c is significantly associated with oxidative stress and an increased risk of cardiovascular disease (CVD. Serum total bilirubin (T-B may have a beneficial role in preventing oxidative changes and be a negative risk factor of CVD. Limited information is available on whether serum T-B is an independent confounding factor of HbA1c. The study subjects were 633 men aged 70 ± 9 (mean ± standard deviation (SD years and 878 women aged 70 ± 8 years who were enrolled consecutively from among patients aged ≥40 years through a community-based annual check-up process. We evaluated the relationship between various confounding factors including serum T-B and HbA1c in each gender. Multiple linear regression analysis pertaining to HbA1c showed that in men, serum T-B ( β = −0.139 as well as waist circumference ( β = 0.099, exercise habit ( β = 0.137, systolic blood pressure (SBP ( β = 0.076, triglycerides ( β = 0.087, and uric acid ( β = −0.123 were significantly and independently associated with HbA1c, and in women, serum T-B ( β = −0.084 as well as body mass index ( β = 0.090, smoking status ( β = −0.077, SBP ( β = 0.117, diastolic blood pressure (DBP ( β = −0.155, low-density lipoprotein cholesterol ( β = 0.074, prevalence of antidyslipidemic medication ( β = 0.174, and uric acid ( β = 0.090 were also significantly and independently associated with HbA1c. Multivariate-adjusted serum HbA1c levels were significantly high in subjects with the lowest serum T-B levels in both genders. Serum T-B is an independent confounding factor for HbA1c among community-dwelling middle-aged and elderly persons.

Conjugated Bilirubin Differentially Regulates CD4+ T Effector Cells and T Regulatory Cell Function through Outside-In and Inside-Out Mechanisms: The Effects of HAV Cell Surface Receptor and Intracellular Signaling

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Corral-Jara, Karla F.; Gómez-Leyva, Juan F.; Rosenstein, Yvonne; Jose-Abrego, Alexis; Roman, Sonia

2016-01-01

We recently reported an immune-modulatory role of conjugated bilirubin (CB) in hepatitis A virus (HAV) infection. During this infection the immune response relies on CD4+ T lymphocytes (TLs) and it may be affected by the interaction of HAV with its cellular receptor (HAVCR1/TIM-1) on T cell surface. How CB might affect T cell function during HAV infection remains to be elucidated. Herein, in vitro stimulation of CD4+ TLs from healthy donors with CB resulted in a decrease in the degree of intracellular tyrosine phosphorylation and an increase in the activity of T regulatory cells (Tregs) expressing HAVCR1/TIM-1. A comparison between CD4+ TLs from healthy donors and HAV-infected patients revealed changes in the TCR signaling pathway relative to changes in CB levels. The proportion of CD4+CD25+ TLs increased in patients with low CB serum levels and an increase in the percentage of Tregs expressing HAVCR1/TIM-1 was found in HAV-infected patients relative to controls. A low frequency of 157insMTTTVP insertion in the viral receptor gene HAVCR1/TIM-1 was found in patients and controls. Our data revealed that, during HAV infection, CB differentially regulates CD4+ TLs and Tregs functions by modulating intracellular pathways and by inducing changes in the proportion of Tregs expressing HAVCR1/TIM-1. PMID:27578921

Diagnostic value of conventional MRI combined with DTI for neonatal hyperbilirubinemia

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Ruifang Yan

2018-04-01

Full Text Available Background: Neonatal hyperbilirubinemia (NHB is a common clinical disease and can cause bilirubin encephalopathy in severe cases. It is now widely accepted that increased signal intensity in the globus pallidus on MR T1WI is an important sign of neonatal bilirubin encephalopathy. And brain diffusion tensor imaging (DTI has not been used extensively to study hyperbilirubinemia (HB. So we compared newborns with different hyperbilirubinemia of different severities and healthy newborns in order to determine the relationships among MRI signal intensities, serum bilirubin levels, and the molecular changes in brain water diffusion in hyperbilirubinemia. Methods: Seventy-three newborns with hyperbilirubinemia were grouped into three groups: the mild increase group (M, 27 cases, the moderate increase group (O, 28 cases, and the severe group (S, 18 cases. The groups were based on serum bilirubin levels. We performed cranial MRI in these newborns, as well as 29 healthy full-term infants (group N. We compared and analyzed the mean signal values for the globus pallidus and the relationship between the bilirubin level and the score on the neonatal behavioral neurological assessment. Fifteen, 10, and 10 patients in groups M, O + S, and N were successfully examined using diffusion tensor imaging (DTI. We assessed the relationships among the signal from the globus pallidus, fractional anisotropy (FA, and average diffusion coefficient (DCav of the posterior limb of the internal capsule (PLIC. Results: There were significant differences in the mean signal value of bilateral globus pallidus between group O/S and group N [p = 0.029 and 0.000 (left, 0.038 and 0.000 (right]. There were no significant differences in bilateral FA or DCav values between the patient groups and group N. The bilateral PLIC-FA and DCav values were significantly different between the patient groups and group N (P = 0.014 and 0.047, respectively. Conclusions: Increased signal intensity

Jaundice

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Jaundice causes your skin and the whites of your eyes to turn yellow. Too much bilirubin causes jaundice. Bilirubin is a yellow chemical in hemoglobin, the ... may look yellow. Many healthy babies have some jaundice during the first week of life. It usually ...

Hemoglobin in samples with leukocytosis can be measured on ABL 700 series blood gas analyzers

NARCIS (Netherlands)

Scharnhorst, V.; Laar, van der P.D.; Vader, H.

2003-01-01

To compare lactate, bilirubin and Hemoglobin F concentrations obtained on ABL 700 series blood gas analyzers with those from laboratory methods. Pooled neonatal plasma, cord blood and adult plasma samples were used for comparison of bilirubin, hemoglobin F and lactate concentrations respectively.

Estimation of liver parameters and oxidative stress in chronic renal failure patients on hemodialysis in Erbil governorate

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Kakey, Musher Ismail Salih; Abdoulrahman, Kamaran Kaiani

2017-09-01

The present study aims to evaluate iron related parameters in chronic renal failure (CRF) patients on hemodialysis (HD). The study was carried out in Kidney Dialysis Center of Hawler Teaching Hospital in Erbil governorate. This study comprised (76) patients with chronic renal failure on hemodialysis and 41 healthy subjects as a control group of same ages. All hemodialysis patients were taking erythropoietin. The blood samples were taken from the patients before and after the process of hemodialysis for liver parameters and oxidative stress estimations. The results of this study showed lower levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin, total bilirubin, total protein and total antioxidant capacity (TAC), while higher levels of alkaline phosphatase (ALP), direct bilirubin and malondialdeyhde (MDA) before analysis was seen. Hemodialysis causes increasing in AST, ALT, albumin, total bilirubin, total protein and decreasing in ALP, direct bilirubin MDA and TAC.

The prevalence of neonatal jaundice and risk factors in healthy term neonates at National District Hospital in Bloemfontein

Science.gov (United States)

2018-01-01

Background Neonatal jaundice affects one in two infants globally. The jaundice is the result of an accumulation of bilirubin as foetal haemoglobin is metabolised by the immature liver. High serum levels of bilirubin result in lethargy, poor feeding and kernicterus of the infant. Aim The main aim of this article was to determine the prevalence of neonatal jaundice and secondly to explore its risk factors in healthy term neonates. Setting Maternity ward, National District Hospital, Bloemfontein, South Africa. Methods In this cross-sectional study, mothers and infants were conveniently sampled after delivery and before discharge. The mothers were interviewed and their case records were reviewed for risk factors for neonatal jaundice and the clinical appearance and bilirubin levels of the infants were measured with a non-invasive transcutaneous bilirubin meter. Results A total of 96 mother-infant pairs were included in the study. The prevalence of neonatal jaundice was 55.2%; however, only 10% of black babies who were diagnosed with jaundice appeared clinically jaundiced. Normal vaginal delivery was the only risk factor associated with neonatal jaundice. Black race and maternal smoking were not protective against neonatal jaundice as in some other studies. Conclusion More than half (55.2%) of healthy term neonates developed neonatal jaundice. As it is difficult to clinically diagnose neonatal jaundice in darker pigmented babies, it is recommended that the bilirubin level of all babies should be checked with a non-invasive bilirubin meter before discharge from hospital or maternity unit as well as during the first clinic visit on day 3 after birth.

A Randomized Controlled Trial of Glycerin Suppositories During Phototherapy in Premature Neonates.

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Butler-O'Hara, Meggan; Reininger, Ann; Wang, Hongyue; Amin, Sanjiv B; Rodgers, Nathan J; D'Angio, Carl T

To determine if glycerin suppositories were effective in reducing total duration of phototherapy in premature neonates. We hypothesized that glycerin suppositories would have no effect on phototherapy duration or total serum bilirubin levels. Prospective randomized controlled double-blinded trial. Level IV NICU. Neonates born between 30 weeks, 0 days and 34 weeks, 6 days gestational age who developed physiologic hyperbilirubinemia needing phototherapy. Neonates were randomized to the no-suppository group or to the suppository group. Neonates were randomized to receive glycerin suppositories every 8 hours while under phototherapy or to a sham group. The primary outcome was total hours of phototherapy. Secondary outcomes included peak total serum bilirubin levels, time from start to discontinuation of phototherapy, rate of decline in bilirubin levels, repeat episodes of phototherapy, and number of stools while the neonates received phototherapy. A total of 39 neonates were assigned to the no-suppository group and 40 to the suppository group. Withholding suppositories was not inferior to providing suppositories. The total hours of phototherapy were not longer (i.e., noninferior) among neonates not provided suppositories (61 ± 53 hours) than among those given suppositories (72 ± 49 hours). There were no differences in peak bilirubin levels, rate of bilirubin decline, or repeat episodes of phototherapy. Routine use of glycerin suppositories among preterm neonates who receive phototherapy does not affect bilirubin levels or phototherapy duration. Copyright © 2017 AWHONN, the Association of Women’s Health, Obstetric and Neonatal Nurses. Published by Elsevier Inc. All rights reserved.

A new diagnostic approach for bilious pleural effusion.

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Saraya, Takeshi; Light, Richard W; Sakuma, Sho; Nakamoto, Yasuo; Wada, Shoko; Ishida, Manabu; Inui, Toshiya; Koide, Takashi; Ishii, Haruyuki; Takizawa, Hajime

2016-09-01

Bilious pleural effusion is an extremely rare condition associated with liver diseases, subphrenic or subhepatic abscess formation, biliary peritonitis, and invasive procedures (i.e., percutaneous biliary drainage or liver biopsy). The current diagnostic test is based on the measurement of the ratio of pleural total bilirubin to serum total bilirubin, which is greater than 1 in patients with bilious pleural effusion. Given the low incidence of bilious pleural effusion, the precise diagnostic yield of this ratio based test has not been evaluated. We retrospectively reviewed the medical records of our institution and searched the PubMed database for reports of bilious pleural effusion. We identified a total of 12 cases of bilious pleural effusion (9 from 8 Pubmed reports and 3 from our institutional records). The factors causing this condition were broadly classified into three categories based on the pathophysiology: 1) liver diseases (echinococcosis, tuberculosis and amebiasis); 2) subhepatic/subphrenic abscess or biliary peritonitis, with or without biliary tract obstruction; and 3) iatrogenic disease after percutaneous biliary drainage and/or liver biopsy. The sensitivity of detection was 76.9% when the ratio of pleural total bilirubin to serum total bilirubin was greater than 1. The sensitivity increased to 100% when a combination test including pleural glycoholic acid was adopted. This study demonstrates the high diagnostic yield for bilious pleural effusion using a combination of two test criteria; a ratio of pleural total bilirubin to serum total bilirubin greater than 1 and the presence of pleural glycoholic acid. Copyright © 2016 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

Haematological and serum biochemical characteristics of weaner ...

African Journals Online (AJOL)

However, monocyte, eosinophil, creatinine, total bilirubin, conjugated bilirubin, aspartate aminotranferase and alanine aminotransferase did not differ (P>0.05) significantly among the treatment means. The result indicated that raw bambara groundnut offal can be incorporated into diet for weaner pigs at 30% level of ...

Novel diode-based laser system for combined transcutaneous monitoring and computer-controlled intermittent treatment of jaundiced neonates

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Hamza, Mostafa; El-Ahl, Mohammad H. S.; Hamza, Ahmad M.

2001-06-01

The high efficacy of laser phototherapy combined with transcutaneous monitoring of serum bilirubin provides optimum safety for jaundiced infants from the risk of bilirubin encephalopathy. In this paper the authors introduce the design and operating principles of a new laser system that can provide simultaneous monitoring and treatment of several jaundiced babies at one time. The new system incorporates diode-based laser sources oscillating at selected wavelengths to achieve both transcutaneous differential absorption measurements of bilirubin concentration in addition to the computer controlled intermittent laser therapy through a network of optical fibers. The detailed description and operating characteristics of this system are presented.

Correlation between chemical components of billary calculi and bile & sera and bile of gallstone patients.

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Chandran, Prasheeda; Garg, Pradeep; Pundir, Chandra S

2005-07-01

Total cholesterol, total bilirubin, calcium, oxalate, inorganic phosphate, magnesium, iron, copper, sodium and potassium were analyzed quantitatively in gallstones, bile of gall bladder and sera of 200 patients of cholelithiasis (52 cholesterol, 76 mixed and 72 pigment stone patients) and their contents were correlated between calculi and bile and sera and bile in these three type of stone patients. A significant positive correlation was observed between total cholesterol, total bilirubin of calculi and bile, copper of bile and sera of cholesterol stone patients, copper of calculi and bile, total bilirubin, oxalate, magnesium, potassium of sera and bile of pigment stone patients and oxalate and iron of stone and bile, total bilirubin, oxalate, sodium of sera and bile of mixed stone patients. A significant negative correlation was found between magnesium of serum and bile of cholesterol stone patients, oxalate of calculi and bile of pigment stone patients and magnesium of serum and bile of mixed stone patients.

Evaluation of Jaundice in Adults.

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Fargo, Matthew V; Grogan, Scott P; Saguil, Aaron

2017-02-01

Jaundice in adults can be an indicator of significant underlying disease. It is caused by elevated serum bilirubin levels in the unconjugated or conjugated form. The evaluation of jaundice relies on the history and physical examination. The initial laboratory evaluation should include fractionated bilirubin, a complete blood count, alanine transaminase, aspartate transaminase, alkaline phosphatase, ?-glutamyltransferase, prothrombin time and/or international normalized ratio, albumin, and protein. Imaging with ultrasonography or computed tomography can differentiate between extrahepatic obstructive and intrahepatic parenchymal disorders. Ultrasonography is the least invasive and least expensive imaging method. A more extensive evaluation may include additional cancer screening, biliary imaging, autoimmune antibody assays, and liver biopsy. Unconjugated hyperbilirubinemia occurs with increased bilirubin production caused by red blood cell destruction, such as hemolytic disorders, and disorders of impaired bilirubin conjugation, such as Gilbert syndrome. Conjugated hyperbilirubinemia occurs in disorders of hepatocellular damage, such as viral and alcoholic hepatitis, and cholestatic disorders, such as choledocholithiasis and neoplastic obstruction of the biliary tree.

Role of extrahepatic UDP-glucuronosyltransferase 1A1: Advances in understanding breast milk-induced neonatal hyperbilirubinemia.

Science.gov (United States)

Fujiwara, Ryoichi; Maruo, Yoshihiro; Chen, Shujuan; Tukey, Robert H

2015-11-15

Newborns commonly develop physiological hyperbilirubinemia (also known as jaundice). With increased bilirubin levels being observed in breast-fed infants, breast-feeding has been recognized as a contributing factor for the development of neonatal hyperbilirubinemia. Bilirubin undergoes selective metabolism by UDP-glucuronosyltransferase (UGT) 1A1 and becomes a water soluble glucuronide. Although several factors such as gestational age, dehydration and weight loss, and increased enterohepatic circulation have been associated with breast milk-induced jaundice (BMJ), deficiency in UGT1A1 expression is a known cause of BMJ. It is currently believed that unconjugated bilirubin is metabolized mainly in the liver. However, recent findings support the concept that extrahepatic tissues, such as small intestine and skin, contribute to bilirubin glucuronidation during the neonatal period. We will review the recent advances made towards understanding biological and molecular events impacting BMJ, especially regarding the role of extrahepatic UGT1A1 expression. Copyright © 2015 Elsevier Inc. All rights reserved.

Phototherapy of the newborn: a predictive model for the outcome.

Science.gov (United States)

Ossamu Osaku, Nelson; Silverio Lopes, Heitor

2005-01-01

Jaundice in one of the most common problems of the newborn. In most cases, jaundice is considered a physiological transient situation, but sometimes it can lead to death or serious injuries for the survivors. For decades, phototherapy has been used as the main method for prevention and treatment of hyperbilirubinaemia of the newborn. This work aims at finding a predictive model for the decrement of blood bilirubin followed conventional phototherapy. Data from 90 patients were collected and used in the multiple regression method. A rigorous statistical analysis was done in order to guarantee a correct and valid model. The obtained model was able to explain 78% of the variation of the dependent variable We found that it is possible to predict the total sugar bilirubin of the patient under phototherapy by knowing its birth weight, bilirubin level at the beginning of treatment, duration of exposition, and irradiance. Besides, it is possible to infer the time necessary for a given decrement of bilirubin, under approximately constant irradiance.

Immobilization of bilirubin oxidase on graphene oxide flakes with different negative charge density for oxygen reduction. The effect of GO charge density on enzyme coverage, electron transfer rate and current density.

Science.gov (United States)

Filip, Jaroslav; Andicsová-Eckstein, Anita; Vikartovská, Alica; Tkac, Jan

2017-03-15

Previously we showed that an effective bilirubin oxidase (BOD)-based biocathode using graphene oxide (GO) could be prepared in 2 steps: 1. electrostatic adsorption of BOD on GO; 2. electrochemical reduction of the BOD-GO composite to form a BOD-ErGO (electrochemically reduced GO) film on the electrode. In order to identify an optimal charge density of GO for BOD-ErGO composite preparation, several GO fractions differing in an average flake size and ζ-potential were prepared using centrifugation and consequently employed for BOD-ErGO biocathode preparation. A simple way to express surface charge density of these particular GO nanosheets was developed. The values obtained were then correlated with biocatalytic and electrochemical parameters of the prepared biocathodes, i.e. electrocatalytically active BOD surface coverage (Γ), heterogeneous electron transfer rate (k S ) and a maximum biocatalytic current density. The highest bioelectrocatalytic current density of (597±25)μAcm -2 and the highest Γ of (23.6±0.9)pmolcm -2 were obtained on BOD-GO composite having the same moderate negative charge density, but the highest k S of (79.4±4.6)s -1 was observed on BOD-GO composite having different negative charge density. This study is a solid foundation for others to consider the influence of a charge density of GO on direct bioelectrochemistry/bioelectrocatalysis of other redox enzymes applicable for construction of biosensors, bioanodes, biocathodes or biofuel cells. Copyright © 2016 Elsevier B.V. All rights reserved.

Role of vitamin C transporters and biliverdin reductase in the dual pro-oxidant and anti-oxidant effect of biliary compounds on the placental-fetal unit in cholestasis during pregnancy

International Nuclear Information System (INIS)

Perez, Maria J.; Castano, Beatriz; Jimenez, Silvia; Serrano, Maria A.; Gonzalez-Buitrago, Jose M.; Marin, Jose J.G.

2008-01-01

Maternal cholestasis causes oxidative damage to the placental-fetal unit that may challenge the outcome of pregnancy. This has been associated with the accumulation of biliary compounds able to induce oxidative stress. However, other cholephilic compounds such as ursodeoxycholic acid (UDCA) and bilirubin have direct anti-oxidant properties. In the present study we investigated whether these compounds exert a protective effect on cholestasis-induced oxidative stress in placenta as compared to maternal and fetal livers, and whether this is due in part to the activation of anti-oxidant mechanisms involving vitamin C uptake and biliverdin/bilirubin recycling. In human placenta (JAr) and liver (HepG2) cells, deoxycholic acid (DCA) similar rates of free radical generation. In JAr (not HepG2), the mitochondrial membrane potential and cell viability were impaired by low DCA concentrations; this was partly prevented by bilirubin and UDCA. In HepG2, taurocholic acid (TCA) and UDCA up-regulated biliverdin-IXα reductase (BVRα) and the vitamin C transporter SVCT2 (not SVCT1), whereas bilirubin up-regulated both SVCT1 and SVCT2. In JAr, TCA and UDCA up-regulated BVRα, SVCT1 and SVCT2, whereas bilirubin up-regulated only SVCT2. A differential response to these compounds of nuclear receptor expression (SXR, CAR, FXR and SHP) was found in both cell types. When cholestasis was induced in pregnant rats, BVRα, SVCT1 and SVCT2 expression in maternal and fetal livers was stimulated, and this was further enhanced by UDCA treatment. In placenta, only BVRα was up-regulated. In conclusion, bilirubin accumulation and UDCA administration may directly and indirectly protect the placental-fetal unit from maternal cholestasis-induced oxidative stress

Hyperbilirubinaemia: its utility in non-perforated appendicitis.

Science.gov (United States)

Sandstrom, Anna; Grieve, David A

2017-07-01

The diagnosis of acute appendicitis is made using clinical findings and investigations. Recent studies have suggested that serum bilirubin, a cheap and simple biochemical test, is a positive predictor in the diagnosis of appendiceal perforation and may be more specific than C-reactive protein (CRP) and white cell count (WCC). The aim of this study was to investigate the utility of the serum bilirubin level in patients with suspected acute but non-perforative appendicitis. A retrospective chart review of 213 patients who presented with suspected appendicitis in a 6-month period to Nambour General Hospital was performed. Serum bilirubin, WCC and CRP were recorded and analysed as to their utility in relation to the final diagnosis. A total of 196 patients underwent an appendicectomy and 41 of these were negative. The specificity of hyperbilirubinaemia for appendicitis overall was 0.83 with a positive predictive value (PPV) of 0.86, compared with CRP (specificity 0.40, PPV 0.75) and WCC (specificity 0.67, PPV 0.85). The area under the receiver operating characteristic curve for bilirubin was 0.6289 compared to 0.6171 for CRP and 0.7219 for WCC. A subgroup analysis of those with complicated appendicitis demonstrated a PPV for bilirubin of 0.66 compared to 0.58 for WCC and 0.34 for CRP in agreement with the literature. Subgroup analysis of hyperbilirubinaemia in simple appendicitis demonstrated a PPV of 0.81 compared to CRP (0.71) and WCC (0.82). Bilirubin had a higher specificity than CRP and WCC overall in patients with appendicitis. Hyperbilirubinaemia had a high PPV in patients with simple appendicitis. © 2015 Royal Australasian College of Surgeons.

REVIEW ARTICLE Conjugated Hyperbilirubinaemia in Early Infancy ...

African Journals Online (AJOL)

REVIEW ARTICLE Conjugated Hyperbilirubinaemia in Early Infancy. AOK Johnson. Abstract. Conjugated hyperbilirubinaemia exists when the conjugated serum bilirubin level is more than 2 mg/dl or more than 20 per cent of the total serum bilirubin. It is always pathological in early infancy. The causes are many and diverse ...

The safety of using the aqueous extract of Ranunculus multifidus ...

African Journals Online (AJOL)

Marizvikuru

2011-03-28

Mar 28, 2011 ... The plant is potentially toxic when used consecutively for a long period. Key words: ... INTRODUCTION ... The productivity of these ... water by means of a bulbed steel needle and groups 2 to 5 .... magnesium, bilirubin total, bilirubin conjugated, GGT and ..... are critical for the maintenance of host defence.

Interaction of indomethacin with adult human albumin and neonatal serum

DEFF Research Database (Denmark)

Honoré, B; Brodersen, R; Robertson, A

1983-01-01

The binding of indomethacin to albumin was investigated at 37 degrees C, pH 7.4. The first stoichiometric binding constant is 2.5 X 10(5) M-1. Indomethacin utilizes both the bilirubin and diazepam binding functions equally. The effect on bilirubin binding to albumin is negligible at therapeutic...

Indications for Laparoscopic Cholecystectomy or Oral Dissolution Therapy with Ursodeoxycholic Acid in Symptomatic Gallstone Disease

Directory of Open Access Journals (Sweden)

Andrea Cariati

2014-06-01

A large Danish study has shown that high bilirubin plasma levels and the genetic variant rs6742078 TT of the enzyme bilirubin glucuronidase UGT1A1 are associated with an increased risk of developing symptomatic gallstone disease. Recent reports regarding the significant association between bilirubin levels and symptomatic gallstone disease open a new chapter about the indication and exclusion criteria for oral dissolution therapy of symptomatic gallstone disease. A highly select subgroup of patients with small, single, radiolucent cholesterol gallstones who received oral dissolution therapy with ursodeoxycholic acid (UDCA had a reported recurrence of symptomatic gallstone disease of 50% over five years. This is probably related to the persistence of other causal risk factors for gallstones in addition to that of cholesterol suprasaturation. A subgroup of patients with high plasma bilirubin levels and the UGT1A1 genetic variant rs6742078 have a greater risk of recurrence. In conclusion, oral dissolution therapy with UDCA might still be appropriate for patients that refuse laparoscopic cholecystectomy provided they have small (< 0.5 cm, radiolucent cholesterol gallstones and a functioning gallbladder, and have mean plasma bilirubin levels below 1.33 mg/dL and are not homozygous for the UGT1A1 rs6742078 TT genotype. [Arch Clin Exp Surg 2014; 3(3.000: 161-165

Effects of Zinc Deuteroporphyrin Bis Glycol on Newborn Mice After Heme-Loading

Science.gov (United States)

He, Cynthia X.; Campbell, Claire M.; Zhao, Hui; Kalish, Flora S.; Schulz, Stephanie; Vreman, Hendrik J.; Wong, Ronald J.; Stevenson, David K.

2011-01-01

Infants with hemolytic diseases frequently develop hyperbilirubinemia, but standard phototherapy only eliminates bilirubin after its production. A better strategy might be to directly inhibit heme oxygenase (HO), the rate-limiting enzyme in bilirubin production. Metalloporphyrins (Mps) are heme analogs that competitively inhibit HO activity in vitro and in vivo and suppress plasma bilirubin levels in vivo. A promising Mp, zinc deuteroporphyrin bis glycol (ZnBG), is orally absorbed and effectively inhibits HO activity at relatively low doses. We determined the I50 (the dose needed to inhibit HO activity by 50%) of orally administered ZnBG in vivo and then evaluated ZnBG’s effects on in vivo bilirubin production, HO activity, HO protein levels, and HO-1 gene expression in newborn mice following heme-loading, a model analogous to a hemolytic infant. The I50 of ZnBG was found to be 4.0 μmol/kg body weight (BW). At a dose of 15-μmol/kg BW, ZnBG reduced in vivo bilirubin production, inhibited heme-induced liver HO activity and spleen HO activity to and below baseline, respectively, transiently induced liver and spleen HO-1 gene transcription, and induced liver and spleen HO-1 protein levels. We conclude that ZnBG may be an attractive compound for treating severe neonatal hyperbilirubinemia caused by hemolytic disease. PMID:21785387

Risk factors of kernicterus; a study in 312 icteric neonates

Directory of Open Access Journals (Sweden)

Behjati Ardakani S

2007-07-01

Full Text Available Background: Kernicterus, also known as bilirubin encephalopathy, is a neurologic syndrome resulting from the deposition of unconjugated bilirubin in the basal ganglia and brainstem nuclei. Indirect bilirubin is toxic for brain. Neurologic dysfunction (BIND that include acute phase (hyperbilirubin encephalopathy and chronic phase (Kernicterus resulting from hyperbilirubinemia and disruption of blood brain barrier. In this study, the association between bilirubin encephalopathy and risk factors was evaluated. Methods: In this retrospective study, 312 icteric neonates were admitted in the neonatal ward of Children's Hospital, Medical Center, Tehran, and 305 of these cases were evaluated. Patient histories were taken and physical examinations were performed. For each patient, the age, sex, birth weight, time of discharge from the hospital and risk factors were recorded, and a questionnaire was completed. Results: In this study, of the 305 icteric neonates evaluated, 25 cases had kernicterus. Risk factors included acidosis, prematurity, hemolysis, hypoglycemia, sepsis, respiratory distress, low birth weight, ABO incompatibility and G6PD deficiency. The mean level of bilirubin in cases of kernicterus was 32 mg/dl and in the others was 20 mg/dl (p=0.001. Kernicterus was most common among high risk neonates (p<0.001. Birth weight less than 2,500 gm was also an important factor (p=0.04. Conclusion: High-risk neonates need prompt treatment for hyperbilirubinemia compared to low risk neonates.

Non-operative management of right side thoracoabdominal penetrating injuries--the value of testing chest tube effluent for bile.

Science.gov (United States)

De Rezende Neto, João Baptista; Guimarães, Tiago Nunes; Madureira, João Lopo; Drumond, Domingos André Fernandes; Leal, Juliana Campos; Rocha, Aroldo; Oliveira, Rodrigo Guimarães; Rizoli, Sandro B

2009-05-01

While mandatory surgery for all thoracoabdominal penetrating injuries is advocated by some, the high rate of unnecessary operations challenges this approach. However, the consequences of intrathoracic bile remains poorly investigated. We sought to evaluate the outcome of patients who underwent non-operative management of right side thoracoabdominal (RST) penetrating trauma, and the levels of bilirubin obtained from those patients' chest tube effluent. We managed non-operatively all stable patients with a single RST penetrating injury. Chest tube effluent samples were obtained six times within (4-8 h; 12-16 h; 20-24 h; 28-32 h; 36-40 h; 48 h and 72 h) of admission for bilirubin measurement and blood for complete blood count, bilirubin, alanine (ALT) and aspartate aminotransferases (AST) assays. For comparison we studied patients with single left thoracic penetrating injury. Forty-two patients with RST injuries were included. All had liver and lung injuries confirmed by CT scans. Only one patient failed non-operative management. Chest tube bilirubin peaked at 48 h post-trauma (mean 3.3+/-4.1 mg/dL) and was always higher than both serum bilirubin (pchest tube effluent from control group (27 patients with left side thoracic trauma). Serum ALT and AST were higher in RST injury patients (ptrauma appears to be safe. Bile originating from the liver injury reaches the right thoracic cavity but does not reflect the severity of that injury. The highest concentration was found in the patient failing non-operative management. The presence of intrathoracic bile in selected patients who sustain RST penetrating trauma, with liver injury, does not preclude non-operative management. Our study suggests that monitoring chest tube effluent bilirubin may provide helpful information when managing a patient non-operatively.

Three-dimensional drip infusion CT cholangiography in patients with suspected obstructive biliary disease: a retrospective analysis of feasibility and adverse reaction to contrast material

International Nuclear Information System (INIS)

Persson, A; Dahlström, N; Smedby, Ö; Brismar, TB

2006-01-01

Computed Tomography Cholangiography (CTC) is a fast and widely available alternative technique to visualise hepatobiliary disease in patients with an inconclusive ultrasound when MRI cannot be performed. The method has previously been relatively unknown and sparsely used, due to concerns about adverse reactions and about image quality in patients with impaired hepatic function and thus reduced contrast excretion. In this retrospective study, the feasibility and the frequency of adverse reactions of CTC when using a drip infusion scheme based on bilirubin levels were evaluated. The medical records of patients who had undergone upper abdominal spiral CT with subsequent three-dimensional rendering of the biliary tract by means of CTC during seven years were retrospectively reviewed regarding serum bilirubin concentration, adverse reaction and presence of visible contrast media in the bile ducts at CT examination. In total, 153 consecutive examinations in 142 patients were reviewed. Contrast media was observed in the bile ducts at 144 examinations. In 110 examinations, the infusion time had been recorded in the medical records. Among these, 42 examinations had an elevated bilirubin value (>19 umol/L). There were nine patients without contrast excretion; 3 of which had a normal bilirubin value and 6 had an elevated value (25–133 umol/L). Two of the 153 examinations were inconclusive. One subject (0.7%) experienced a minor adverse reaction – a pricking sensation in the face. No other adverse effects were noted. We conclude that drip infusion CTC with an infusion rate of the biliary contrast agent iotroxate governed by the serum bilirubin value is a feasible and safe alternative to MRC in patients with and without impaired biliary excretion. In this retrospective study the feasibility and the frequency of adverse reactions when using a drip infusion scheme based on bilirubin levels has been evaluated

PIPIDA excretory scintigraphy in the diagnosis of hepatobiliary disorders

International Nuclear Information System (INIS)

Pelot, D.; Berk, J.E.; Wistow, B.W.; Morton, M.E.

1981-01-01

The diagnostic accuracy of hepatobiliary radionuclide imaging using 99 mTC-labeled para-isopropyl acetanilido-iminodiacetic acid ( 99 mTc-PIPIDA) in patients with hepatobiliary disorders was assessed in 50 patients. Thirty of the study group were jaundiced; the remaining 20 had other clinical features suggestive of some hepatobiliary disorder. The findings using PIPIDA proved to be correct in 22 (73%) of the 30 jaundiced patients and in 18 (90%) of 20 patients without jaundice. There appears to be a close relationship between the diagnostic accuracy of the test and the level of serum bilirubin. Thus, the diagnosis indicated by the PIPIDA test was correct in 30 (88%) of 34 patients in whom the serum bilirubin was less than 5 mg./dl. but only in 10 (62%) of 16 patients whose serum bilirubin exceeded 5 mg./dl. It is concluded from these observations that: 1. PIPIDA is diagnostically useful in the evaluation of hepatobiliary disorders, especially when the serum bilirubin is less than 5 mg./dl. and 2. the accuracy of this test is not absolute and the findings are not always definitive

Analysis of human gallstones by FTIR

International Nuclear Information System (INIS)

Channa, Naseem A.; Khand, Fateh D.

2008-01-01

The present study was aimed at determining the composition of gallstones removed from patients in Southern Sindh, Pakistan. 109 gallstone samples surgically removed from as many patients (98 females and 11 males; age range 20 to 80 years) admitted for treatment in Liaquat University hospital, Jamshsoro during 2000 to 2003, were analyzed for composition by Fourier Transform Infrared (FTIR) spectroscopy. 74 (67.9%) of the 109 gallstone samples were found to be pure cholesterol stones, 5 (4.6%) pure calcium carbonate stones, 13 (11.9%) cholesterol + calcium carbonate, 10 (9.2%) cholesterol + bilirubin and 07 (6.4%) calcium bilirubinate stones. In mixed composition gallstones cholesterol was concentrated more at periphery than in the center of stone. Cholesterol either singly (67.9%) or in combination with either calcium carbonate (11.9%) or bilirubin (9.2%) was the most predominant component of gallstones. Analysis of gallstones based on FTIR suggests that cholesterol either singly or in combination with either calcium carbonate or bilirubin is the most predominant component of gallstones from Southern Sindh, Pakistan. (author)

Tc-99m-diethyl-IDA imaging: clinical evaluation in jaundiced patients

International Nuclear Information System (INIS)

Pauwels, S.; Piret, L.; Schoutens, A.; Vandermoten, G.; Beckers, C.

1980-01-01

Hepatobiliary imaging with Tc-99m-N,α-(2,6-diethylacetanilide)-iminodiacetic acid (Tc-diethyl-IDA) was performed in 91 jaundiced patients with documented hepatobiliary damage and serum total bilirubin up to 35 mg/dl. There were 56 patients with obstructive jaundice and 35 with hepatocellular disease. Correct discrimination between hepatocellular and obstructive jaundice was possible with an overall accuracy of 90%. Agreement with the final clinical diagnosis was obtained in 97% of patients with hepatocellular disease, and in 86% of patients with obstructive jaundice. The reliability of the test was inversely related to the serum bilirubin levels below 10 mg/dl to 83% for bilirubin between 10 and 20 mg/dl. Above 20 mg/dl, the demonstration of a mechanical obstruction was possible in only one out of the four patients with obstructive jaundice. The high predictive values of the test illustrate that Tc-diethyl-IDA imaging constitutes a reliable method to demonstrate an obstructive cause for the jaundice as long as the bilirubin level remains below 20 mg/dl

Refinement of exclusionary criteria for lithotripsy

International Nuclear Information System (INIS)

Trefeiner, E.; Burrell, M.; McCarthy, S.; Rosenfield, A.

1989-01-01

This paper reports gallstones from 200 cholecystectomy patients examined with CT, US, and MR imaging. On CT scans, stones of over 50 HU had a mean bilirubinate content of 23%, versus 6.2% in those less than 50 HU. Forty-four percent of stones had MR signal on both T1- and T2-weighted images. When compared with stones without signal, these also has significantly higher CT numbers. Chemical shift imaging identified the signal as water protons. Therefore, stones above 50 HU are probably poor candidates for lithotripsy because of the increased concentrations of calcium bilirubinate and carbonate. The associated increased incidence of MR signal may be attributed to layers of water associated with bilirubinate salts

Violation of specific indicators pigment and lipid metabolism in experimental pneumonia in an immobilization stress and correction of corvitin

Directory of Open Access Journals (Sweden)

N. M. Ferenc

2015-09-01

  Abstract   The aim of study was to investigate the features change cholesterol and bilirubin in the blood serum of guinea pigs (males with experimental pneumonia (EP under conditions of immobilization stress (IS and prove the feasibility of Corvitin. The study was conducted on 48 guinea pigs (males were divided into 6 groups. The research results make it possible to detect liver damage in terms of IS EP and in violation of its functional state. Application domestic preparation Corvitin led to a significant reduction in the changed parameters bilirubin and cholesterol under conditions of formation of EP and IP, which indicates its positive corrective effect.   Keywords: experimental pneumonia, stress, liver, cholesterol, bilirubin.

Clinical use of 99mTc mebrofenin

International Nuclear Information System (INIS)

Chen Shaoliang; Zhao Huiyang

1989-01-01

A study of 124 subjects was undertaken to evaluate the image patterns of 99m Tc trimethylbromo iminodiacetic acid ( 99m Tc mebrofenin) in hepatobiliary disorders. It exhibits: (a) high specificity for the hepatobiliary system with low urinary excretion rate; (b) high competition to bilirubin; and (c) clearing more rapidly from the blood and rapid transit through the hepatobiliary system. Therefore 99m Tc mebrofenin result in the best visualization of the biliary system either in nonjaundiced or joundiced patient, and the hepatobiliary system can be clearly visualized even in patients with serum bilirubin level up to 30 mg%. The major drawback of this agent is that the urinary excretion rate increased in case of high serum bilirubin

Concept of BuBc in neonatal jaundice – needs a change

OpenAIRE

Singh, Kalpana; Borrison, Auxilia; Mahdi, Abbas Ali

2014-01-01

Orthoclinical diagnostics Vitros microslide came with a method by which Bu and Bc can be estimated directly. The advantage of this microslide technology is that conjugated bilirubin (Bc) does not contain delta bilirubin and the fractions i.e BuBc are actually estimated. TBil estimation is also available based on traditional diazo method on the same instrument

[Usefullness of the Kramer's index in the diagnosis of hyperbilirubinemia of the newborn].

Science.gov (United States)

Acosta-Torres, Sara M; Torres-Espina, Marco T; Colina-Araujo, José A; Colina-Chourio, José A

2012-06-01

The objective of the present study was to correlate seric values of bilirubin with the Kramer's index in a group of newborns with neonatal jaundice, from three different ethnic groups. This was a prospective, randomized, observational, descriptive-analytical, longitudinal, comparative and controlled study of 50 newborns with neonatal jaundice, without complications. They were divided into three groups: A (Control), n = 25, of Caucasian descent; B, n = 15, of local indigenous descent (Wayúu) and C, n = 10, of Afro-American descent. Each newborn was screened at the start of the study for their Kramer's dermic areas and simultaneously, a venous blood sample from the arm was taken for bilirubin quantification. They were compared through a correlation-regression analysis. Values at the beginning of the study were: serum bilirubin 12.02 +/- 3.41 mg/dL, and 62.8% of neonates were at Kramer's level 3. There were no differences among the ethnic groups studied and the correlation bilirubin/Kramer's index was r= 0.93 (p < 0.005). At the third day, both bilirubin and Kramer's indexes started to decrease. There were no ethnic differences. In conclusion, the Kramer's method offers multiple advantages to evaluate a jaundiced newborn; it is a safe, non-invasive method with no cost. Besides, it is of great help in the prevention of the kernicterus. It is recommended to implement the use of the Kramer method in all the newborns units in our Hospitals, preferably in those lacking transcutaneous bilirubinometers.

Carboxyhemoglobin - the forgotten parameter of neonatal hyperbilirubinemia.

Science.gov (United States)

Bailey, Douggl G N; Fuchs, Hans; Hentschel, Roland

2017-07-26

Neonatal hyperbilirubinemia is influenced by a wide variety of factors, one of which is hemolysis. Serious hyperbilirubinemia may lead to a kernicterus with detrimental neurologic sequelae. Patients suffering from hemolytic disease have a higher risk of developing kernicterus. Carbon monoxide (CO), a byproduct of hemolysis or heme degradation, was described by Sjöstrand in the 1960s. It is transported as carboxyhemoglobin (COHb) and exhaled through the lungs. We were interested in a potential correlation between COHb and total serum bilirubin (TSB) and the time course of both parameters. We used a point of care (POC) blood gas analyzer and did a retrospective analysis of bilirubin and COHb data collected over a 60-day period. An arbitrary cut-off point set at 2% COHb identified four patients with hemolytic disease of different origins who required phototherapy. In one patient with atypical hemolytic uremic syndrome (aHUS), COHb preceded the rise in bilirubin by about 2 days. Despite this displacement, there was a moderately good correlation of COHb with TSB levels <15 mg/dL (257 μmol/L) (r2: 0.80) and direct bilirubin (r2: 0.78) in the first patient. For all the four patients and all time points the correlation was slightly lower (r2: 0.59). COHb might be useful as a marker for high hemoglobin turnover to allow an earlier identification of newborns at risk to a rapid rise in bilirubin.

Hyperbilirubinaemia and erythrocytic glucose 6 phosphate dehydrogenase deficiency in Malaysian children.

Science.gov (United States)

Hon, A T; Balakrishnan, S; Ahmad, Z

1989-03-01

Cord blood from 8,975 babies delivered in Hospital Sultanah Aminah Johor Bahru over a period of eight months (1st August 1985 to 31st March 1986) were screened for G6PD deficiency. The overall incidence was 4.5% in Chinese, 3.5% in Malays and 1.5% in Indian babies. One hundred of these babies were observed in the nursery for seven days and their daily serum bilirubin recorded. The serum bilirubin peaked at 96 hours to a value of 12mg%. None of the babies in the nursery developed a serum bilirubin level of more than 15mg%. Six of the babies with G6PD deficiency that were sent home were readmitted with hyperbilirubinaemia that needed exchange transfusion.

[Neonatal hyperbilirubinemia and molecular mechanisms of jaundice].

Science.gov (United States)

Jirsa, M; Sticová, E

2013-07-01

The introductory summarises the classical path of heme degradation and classification of jaundice. Subsequently, a description of neonatal types of jaundice is given, known as Crigler Najjar, Gilberts, DubinJohnson and Rotor syndromes, emphasising the explanation of the molecular mechanisms of these metabolic disorders. Special attention is given to a recently discovered molecular mechanism of the Rotor syndrome. The mechanism is based on the inability of the liver to retrospectively uptake the conjugated bilirubin fraction primarily excreted into the blood, not bile. A reduced ability of the liver to uptake the conjugated bilirubin contributes to the development of hyperbilirubinemia in common disorders of the liver and bile ducts and to the toxicity of xenobiotics and drugs using transport proteins for conjugated bilirubin.

Effect of different pectin on bile acid biosynthesis

International Nuclear Information System (INIS)

Khalikova, M.D.; Mukhiddinov, Z.K.; Nuraliev, Yu.N.; Khaydarov, K.Kh.

2009-01-01

The objective of the study was to examine the effects of consumption of different pectins from peach, quince, and apricot on bile flow and bile secretion of bile acids, cholesterol, phospholipids and bilirubin in rats. Six groups of nine rats were fed diets containing pectin 20 mg/kg once a day for two weeks. These groups of rats were compared with the group fed on physiological solution as a control and two groups fed on flamenol. Results of our study indicate that pectins, by decreasing cholesterol levels and enhancing bile acid secretion may cause increased hepatic synthesis of bile acids, phospholipids and reduced bilirubin synthesis. Among the studied pectins the apricot pectin shows in a very consistent lowering of cholesterol and bilirubin levels

Severe Hemolysis in a Patient With Erythrocytosis During Coupled Plasma Filtration Adsorption Therapy Was Prevented by Changing From Membrane-Based Technique to a Centrifuge-Based One.

Science.gov (United States)

Fan, Rong; Wu, Buyun; Kong, Ling; Gong, Dehua

2016-01-01

Coupled plasma filtration adsorption (CPFA) usually adopts membrane to separate plasma from blood. Here, we reported a case with erythrocytosis experienced severe hemolysis and membrane rupture during CPFA, which was avoided by changing from membrane-based technique to a centrifuge-based one. A 66-year-old man was to receive CPFA for severe hyperbilirubinemia (total bilirubin 922 μmol/L, direct bilirubin 638 μmol/L) caused by obstruction of biliary tract. He had erythrocytosis (hemoglobin 230 g/L, hematocrit 0.634) for years because of untreated tetralogy of Fallot. Severe hemolysis and membrane rupture occurred immediately after blood entering into the plasma separator even at a low flow rate (50 mL/min) and persisted after changing a new separator. Finally, centrifugal plasma separation technique was used for CPFA in this patient, and no hemolysis occurred. After 3 sessions of CPFA, total bilirubin level decreased to 199 μmol/L with an average decline by 35% per session. Thereafter, the patient received endoscopic biliary stent implantation, and total bilirubin level returned to nearly normal. Therefore, centrifugal-based plasma separation can also be used in CPFA and may be superior to a membrane-based one in patients with hyperviscosity.

Application of dry elixir system to oriental traditional medicine: taste masking of peonjahwan by coated dry elixir.

Science.gov (United States)

Choi, H G; Kim, C K

2000-02-01

Peonjahwan, an oriental traditional medicine composed of crude herbal drugs and animal tissues is bitter and poorly water-soluble. To mask the bitterness of peonjahwan and enhance the release of bilirubin, one of the crude active ingredients of peonjahwan, peonja dry elixir (PDE), was prepared using a spray-dryer after extracting the crude materials in ethanol-water solution. Coated peonja dry elixir (CPDE) was then prepared by coating the PDE with Eudragit acrylic resin. Panel assessed bitterness and release test of bilirubin from PDE and CPDE were carried out and compared with peonjahwan alone. PDE was found to have little effect upon the reduction of the bitterness of peonjahwan. However, the bitterness of CPDE was found to reduce to 1/4 of that of peonjahwan due to the encapsulation of crude active ingredients by the dextrin and Eudragit shell (P<0.05). The release rate of bilirubin from PDE and CPDE for 60 min increased about 3.5- and 2.5- fold, respectively, compared to peonjahwan at pH 1.2. It is concluded that CPDE, which masked the bitterness of peonjahwan and enhanced the release of bilirubin, is a preferable delivery system for peonjahwan.

Phototherapy of neonatal hyperbilirubinemia

International Nuclear Information System (INIS)

Moan, J.

1992-01-01

In a significant fraction of newborns the skin becomes yellow for a few days after birth due to accumulation of bilirubin, a product of heme catabolism. If the concentration of bilirubin in the serum approches the binding capacity of albumin, bilirubin may penetrate into the central nervous system and cause irreversible damage. Phototherapy is the most common form of therapy, used on 5 to 10% of all newborns in Norway. Three photochemical reactions are of importance in this treatment: Photooxydation of bilirubin followed by fragmentation of the molecule and formation of watersoluble products. Reversible formation of (4Z,15E) and (less important) (4E,15Z) configurational isomers. Irreversible formation of the structure isomer Z-lumirubin, which is relatively water-soluble and can be excreted. The (4E,15Z) isomer is probably an intermediate in the formation of Z-lumirubin, whose formation therefore requires the absorption of two photons. Irreversible formation of Z-lumirubin, which has a quantum yield that increases with increasing wavelength of the light, is believed to be the most important reaction in phototherapy. All known side-effects of phototherapy are transient and not serious. 16 refs., 8 figs

Evanescent field: A potential light-tool for theranostics application

Science.gov (United States)

Polley, Nabarun; Singh, Soumendra; Giri, Anupam; Pal, Samir Kumar

2014-03-01

A noninvasive or minimally invasive optical approach for theranostics, which would reinforce diagnosis, treatment, and preferably guidance simultaneously, is considered to be major challenge in biomedical instrument design. In the present work, we have developed an evanescent field-based fiber optic strategy for the potential theranostics application in hyperbilirubinemia, an increased concentration of bilirubin in the blood and is a potential cause of permanent brain damage or even death in newborn babies. Potential problem of bilirubin deposition on the hydroxylated fiber surface at physiological pH (7.4), that masks the sensing efficacy and extraction of information of the pigment level, has also been addressed. Removal of bilirubin in a blood-phantom (hemoglobin and human serum albumin) solution from an enhanced level of 77 μM/l (human jaundice >50 μM/l) to ˜30 μM/l (normal level ˜25 μM/l in human) using our strategy has been successfully demonstrated. In a model experiment using chromatography paper as a mimic of biological membrane, we have shown efficient degradation of the bilirubin under continuous monitoring for guidance of immediate/future course of action.

An extended chemical analysis of gallstone

OpenAIRE

Chandran, P.; Kuchhal, N. K.; Garg, P.; Pundir, C. S.

2007-01-01

Chemical composition of gall stones is essential for aetiopathogensis of gallstone disease. We have reported quantitative chemical analysis of total cholesterol bilirubin, calcium, iron and inorganic phosphate in 120 gallstones from haryana. To extend this chemical analysis of gall stones by studying more cases and by analyzing more chemical constituents. A quantitative chemical analysis of total cholesterol, total bilirubin, fatty acids, triglycerides, phospholipids, bile acids, soluble prot...

Role of extrahepatic UDP-glucuronosyltransferase 1A1: advances in understanding breast milk-induced neonatal hyperbilirubinemia

OpenAIRE

Fujiwara, Ryoichi; Maruo, Yoshihiro; Chen, Shujuan; Tukey, Robert H.

2015-01-01

Newborns commonly develop physiological hyperbilirubinemia (also known as jaundice). With increased bilirubin levels being observed in breast-fed infants, breast-feeding has been recognized as a contributing factor for the development of neonatal hyperbilirubinemia. Bilirubin undergoes selective metabolism by UDP-glucuronosyltransferase (UGT) 1A1 and becomes a water soluble glucuronide. Although several factors such as gestational age, dehydration and weight loss, and increased enterohepatic ...

Pleiotropic effects of HNF1A rs1183910 in a population-based study of 60,283 individuals

DEFF Research Database (Denmark)

Allin, Kristine H; Nordestgaard, Børge G

2014-01-01

with increased levels of non-fasting plasma glucose (p(trend) = 3 × 10(-5)), apolipoprotein B (ApoB; p(trend) = 1 × 10(-4)) and alkaline phosphatase (p(trend) = 5 × 10(-14)), and decreased levels of bilirubin (p trend = 3 × 10(-5)). Our results suggest that the association with increased risk of type 2 diabetes...... effects through decreased levels of CRP, γ-glutamyltransferase and bilirubin....

Measurements and monitoring of phototherapy in newborn jaundice

International Nuclear Information System (INIS)

Sisson, T.R.

1982-01-01

Hyperbilirubinemia in the newborn (neonatal jaundice) may cause irreversible brain damage if plasma concentrations of bilirubin exceed the number of binding sites on albumin and other blood components. Phototherapy or exchange transfusions to prevent the excessive rise in concentration of the pigment should be instituted in appropriate clinical situations. In phototherapy, the jaundiced infant is exposed to visible light containing the wavelength (about 450 nm) bilirubin will absorb. Because bilirubin is quite photolabile and will readily isomerize in vivo, it is rapidly converted to excretable forms. The effectiveness of this therapy, however, depends upon the maintenance of adequate radiant flux in the required wavelength. Energy output and spectral distributions of phototherapy lamps must be measured. The long-term effects of irradiation of newborn infants over several days are not yet known

Prognostic value of Child-Turcotte criteria in medically treated cirrhosis

DEFF Research Database (Denmark)

Christensen, E; Schlichting, P; Fauerholdt, L

1984-01-01

The Child- Turcotte criteria (CTC) (based on serum bilirubin and albumin, ascites, neurological disorder and nutrition) are established prognostic factors in patients with cirrhosis having portacaval shunt surgery. The objective of this study was to evaluate the prognostic value of CTC in conserv......The Child- Turcotte criteria (CTC) (based on serum bilirubin and albumin, ascites, neurological disorder and nutrition) are established prognostic factors in patients with cirrhosis having portacaval shunt surgery. The objective of this study was to evaluate the prognostic value of CTC...... compared using the log-rank test. Survival decreased significantly with increasing degree of abnormality (A----B----C) of albumin (p less than 0.001), ascites (p less than 0.001), bilirubin (p = 0.02) and nutritional status (p = 0.03). Survival was insignificantly influenced by neurological status (p = 0...

Prognosis of external radiotherapy for unresected bile duct carcinoma

International Nuclear Information System (INIS)

Hirokawa, Yutaka; Kashiwado, Kozo; Kashimoto, Kazuki

1991-01-01

Thirty two patients with unresectable bile duct carcinoma were treated with external irradiation. The outcome of these patients was retrospectively analyzed in terms of survival time and prognostic variables. Nine prognostic variables were examined as follows: sex, performance status, age, radiation doses; irradiation fields, the presence or absence of chemotherapy, values of lactic dehydrogenase before the beginning of treatment, total bilirubin values, and hemoglobin values. In all patients, median survival was 7.3 months, and one-year survival time was 34.4%. The most significant prognostic variable was total radiation doses, followed by performance status, total bilirubin values, and irradiation fields. Higher survival rate was associated with 60 Gy or more doses, the combination of UFT chemotherapy, and 4 mg/dl or less of total bilirubin values. (N.K.)

Evaluation of the correlation between transcutaneous measurement andconcentration ofbilirubin inthe blood serum ofa newborn

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Małgorzata Morawiecka-Pietrzak

2016-09-01

Full Text Available Aim: Due to the potential toxicity of high concentrations of bilirubin, newborns are monitored in terms of the potential emergence of a group at risk of the development of severe hyperbilirubinaemia and, rarely, encephalopathy and kernicterus. The transcutaneous measurement of bilirubin, as a non-invasive method, is applied in neonatal centres. The paper presents an evaluation of the correlation between the transcutaneous measurement and the concentration of bilirubin in the blood serum of a newborn, taking into consideration the reduction of the necessity to carry out blood tests related to the transcutaneous measurement. Material and method: The analysis comprised 1,076 medical histories of newborns hospitalised at the Department of Neonatology of the Municipal Hospital in Zabrze in the period from 1 January to 31 December 2013 (a primary referral centre. The inclusion criteria for the study were: performing a simultaneous transcutaneous measurement and a blood serum concentration measurement of bilirubin, gestational age ≥35 Hbd and birth weight >2,500 g. 272 children were qualified for the study. Results: Boys constituted 51.7%, and girls 48.3% of the research group. The mean gestational age was 38.7 Hbd and the mean birth weight was 3,323.4 g; 67.8% of the children were born by natural labour and 32.2% – by caesarean section. The mean Apgar score in the 5th minute was 9.8 points. The measurement of the concentration of bilirubin was performed on average on the 3.9 day of life. The mean transcutaneous measurement was 9.67 mg% (2.7–17.2 mg% and the mean concentration of bilirubin in the blood serum was 13.18 mg% (7.0–19.8 mg%; the difference was 3.5 mg% (p < 0.0001. A statistically significant positive correlation was found between the concentrations of bilirubin obtained in the transcutaneous measurement and the concentrations in the blood serum (according to Spearman, r

Correlation between chemical components of billary calculi and bile & sera and bile of gallstone patients

OpenAIRE

Chandran, Prasheeda; Garg, Pradeep; Pundir, Chandra S.

2005-01-01

Total cholesterol, total bilirubin, calcium, oxalate, inorganic phosphate, magnesium, iron, copper, sodium and potassium were analyzed quantitatively in gallstones, bile of gall bladder and sera of 200 patients of cholelithiasis (52 cholesterol, 76 mixed and 72 pigment stone patients) and their contents were correlated between calculi and bile and sera and bile in these three type of stone patients. A significant positive correlation was observed between total cholesterol, total bilirubin of ...

Identification of pathogens for differential diagnosis of fever with jaundice in the Central African Republic: a retrospective assessment, 2008–2010

OpenAIRE

Gadia, Christelle Luce Bobossi; Manirakiza, Alexandre; Tekpa, Gaspard; Konamna, Xavier; Vickos, Ulrich; Nakoune, Emmanuel

2017-01-01

Background Febrile jaundice results clinically in generalized yellow coloration of the teguments and mucous membranes due to excess plasma bilirubin, accompanied by fever. Two types are found: conjugated and unconjugated bilirubin jaundice. Jaundice is a sign in several diseases due to viruses (viral hepatitis and arbovirus), parasites (malaria) and bacteria (leptospirosis). In the Central African Republic (CAR), only yellow fever is included on the list of diseases for surveillance. The aim ...

Identification of cellular targets for specific therapies in neurodevelopmental disorders

OpenAIRE

Vaz, Ana Rita Mendonça, 1984-

2010-01-01

Tese de doutoramento, Farmácia (Biologia Celular e Molecular), Universidade de Lisboa, Faculdade de Farmácia, 2010 The present dissertation is focused in neonatal hyperbilirubinemia, a very common condition in the neonatal period, characterized by increased concentrations of unconjugated bilirubin (UCB). High levels of UCB may lead to bilirubin-induced neurologic dysfunction (BIND), particularly in premature infants, which may be a starting point to the appearance of long-term ...

Screening of Glucose-6-Phosphate Dehydrogenase Deficiency in Cord Blood

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Can Acipayam

2014-02-01

Aim: Glucose-6-phosphate dehydrogenase deficiency is an important factor in etiology of pathologic neonatal jaundice. The aim of this study was to indicate the significance of screening glucose-6-phosphate dehydrogenase deficiency in the cord blood of neonates and the frequency of this deficiency in the etiology of neonatal hyperbilirubinemia. Material and Method: The study was performed consecutive 1015 neonates were included. Five hundred fifty six (54.8% of them were male and 459 (45.2% were female. The following parameters were recorded: Gender, birth weight, birth height, head circumference and gestational age. The glucose-6-phosphate dehydrogenase level of neonates were measured with quantitative method in cord blood. Also, hemoglobine, hematocrite, red blood cell count and blood group were measured. The following parameters were recorded in cases with jaundice: exchange transfusion, phototherapy, physiologic and pathologic jaundice, peak bilirubin day, maximum bilirubin level, total bilirubin level at the first day of jaundice, beginning time of jaundice. Results: Enzyme deficiency was detected in 133 (13.1% of neonates and 76 (57% of them were male, 57 (43% were female. Significant difference was detected in low glucose-6-phosphate dehydrogenase enzyme level with jaundice group for total bilirubin level at the first day of jaundice, maximum total bilirubin level and pathologic jaundice (p<0.05. Discussion: The ratio of glucose-6-phosphate dehydrogenase deficiency was found in Edirne in this study and this ratio was higher than other studies conducted in our country. For this reason, glucose-6-phosphate dehydrogenase enzyme level in cord blood of neonates should be measured routinely and high risk neonates should be followed up for hyperbilirubinemia and parents should be informed in our region.

Development and optimization of a noncontact optical device for online monitoring of jaundice in human subjects

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Polley, Nabarun; Saha, Srimoyee; Singh, Soumendra; Adhikari, Aniruddha; Das, Sukhen; Choudhury, Bhaskar Roy; Pal, Samir Kumar

2015-06-01

Jaundice is one of the notable markers of liver malfunction in our body, revealing a significant rise in the concentration of an endogenous yellow pigment bilirubin. We have described a method for measuring the optical spectrum of our conjunctiva and derived pigment concentration by using diffused reflection measurement. The method uses no prior model and is expected to work across the races (skin color) encompassing a wide range of age groups. An optical fiber-based setup capable of measuring the conjunctival absorption spectrum from 400 to 800 nm is used to monitor the level of bilirubin and is calibrated with the value measured from blood serum of the same human subject. We have also developed software in the LabVIEW platform for use in online monitoring of bilirubin levels in human subjects by nonexperts. The results demonstrate that relative absorption at 460 and 600 nm has a distinct correlation with that of the bilirubin concentration measured from blood serum. Statistical analysis revealed that our proposed method is in agreement with the conventional biochemical method. The innovative noncontact, low-cost technique is expected to have importance in monitoring jaundice in developing/underdeveloped countries, where the inexpensive diagnosis of jaundice with minimally trained manpower is obligatory.

Hepatobiliary gammagraphy and its importance for differential diagnosis of mechanic and hepatocellular jaundice

International Nuclear Information System (INIS)

Takacs, J.

1983-01-01

The reliability of hepatobiliary gammagraphy following sup(99m)Tc-EHIDA administration and its variations with the concentration of the total plasma bilirubin were assessed in 155 hepatitis patients in whom differential diagnosis was performed for mechanical or hepatocellular jaundice. In mechanical jaundice (28 patients), sensitivity of the method was 75.8%, specificity 95.9%, diagnostic accuracy 90.9%. In hepatocellular jaundice (127 patients) the respective values were 95.9%, 90.3%, 94.8%. The differential diagnosis reliability was found to decrease with the increasing level of total bilirubin. For a level of up to 21.5 μmol/l, diagnostic accuracy was 93.6%, for a level between 21.6 and 85.5 μmol/l it was 91.0%, from 85.6 to 171.0 μmol/l it was 66.6%, from 171.1 to 242.0 μmol/l it was 50.0%, and above 242.0 μmol/l, diagnostic accuracy was 28.5%. At the same time, the sensitivity and specificity of examination decreased with increasing bilirubin level. In respect of differential diagnosis of jaundice, a concentration of the total plasma bilirubin of 242.O μmol/l is considered to be the limit concentration. (author)

Refractory obstructive jaundice in a child affected with thalassodrepanocytosis: a new endoscopic approach

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Barresi Luca

2010-10-01

Full Text Available Abstract Background Liver involvement, including elevated direct-reacting bilirubin levels, is common in patients with sickle cell disease. Fifty to seventy percent of sickle cell patients have pigmented gallstones due to precipitation of unconjugated bilirubin, and cholelithiasis or choledocholithiasis are common complications. The highest prevalence of these complications occurs in patients with Gilbert's syndrome because of the combined effect of increased bilirubin production and reduced bilirubin-diphosphate-glucuronosyltransferase enzyme activity. Cholelithiasis is also a common complication in patients with thalassemia. Endoscopic removal of choledochal stones does not always resolve the clinical picture, as in cases of dysfunction of the Vater's papilla, increased bile density due to persistently impaired bile flow or distortion of the choledocus due to dilatation, or inflammation secondary to gallstone. Case presentation We report here a case of severe and persistent obstructive jaundice in a child affected with thalassodrepanocytosis and Gilbert's syndrome, previously, and unsuccessfully, treated with endoscopic removal of choledochal stones. Deep and thorough biliary washing, and stenting with a new removable polytetrafluoroethylene (PTFE-covered flared-type stent led to complete resolution of the obstructive jaundice. Conclusions This report shows that an aggressive endoscopic approach in this select category of patients can help resolve the severe complication of hemolytic anemia, thus avoiding surgery.

Follow-up of extreme neonatal hyperbilirubinaemia in 5- to 10-year-old children

DEFF Research Database (Denmark)

Vandborg, Pernille Kure; Hansen, Bo Mølholm; Greisen, Gorm

2015-01-01

AIM: To investigate whether infants with neonatal hyperbilirubinaemia but without intermediate or advanced bilirubin encephalopathy develop long-term sequelae, with impairment of motor development, executive function, or hearing. METHOD: This nested double-cohort study included 167 exposed children...... (107 males, 60 females) born in Denmark 2000 to 2005 at gestational age ≥35 weeks with a total serum bilirubin ≥450 μmol/L (26.3mg/dL) and 163 age-, sex-, and gestational age-matched unexposed children (103 males, 60 females). The children were examined at a mean age of 7.7 years (SD 1.7y) using...... spectrum disorder recorded in national registries. INTERPRETATION: No evidence was found of an increased risk of deficits in motor development, executive function, or hearing in children with extreme hyperbilirubinaemia who did not have intermediate or advanced bilirubin encephalopathy....

ESPGHAN Committee on Nutrition Position Paper. Intravenous lipid emulsions and risk of hepatotoxicity in infants and children

DEFF Research Database (Denmark)

Hojsak, Iva; Colomb, Virginie; Braegger, Christian

2016-01-01

The aim of this paper was to perform a systematic review with meta-analysis of available scientific evidence regarding the role of different intravenous lipid emulsions (ILE) in the pathogenesis of cholestasis and parenteral nutrition associated liver disease (PNALD).A systematic review...... term use and 3 in infants and children receiving long term parenteral nutrition (PN).Meta-analysis showed no differences in the rate of cholestasis or bilirubin levels associated with short term use of different ILEs. Due to high heterogeneity of the long-term studies no meta-analysis could...... of patients. The ESPGHAN Committee on Nutrition concludes that there is no evidence of a difference in rates of cholestasis or bilirubin levels between different ILE for short term use in neonates. The use of multicomponent FO containing ILE may contribute to a decrease in total bilirubin levels in children...

Technetium-99m biliary imaging in pediatric surgical problems

International Nuclear Information System (INIS)

Sty, J.R.; Glicklich, M.; Babbitt, D.P.; Starshak, R.J.

1981-01-01

The results of scintigraphic imaging of the hepatobiliary system with 99mTc-PIPIDA (IDA derivative p-isopropylacetanilidoiminodiacetic acid) in forty children are reported. 99mTc-PIPIDA imaging is a noninvasive, rapid, safe examination that provides both functional and anatomical information about the hepatobiliary system. Although interpretation is limited by elevated direct serum bilirubin, this agent allows diagnostic information to be obtained with direct serum bilirubin levels up to 8 mg/dl

Practice patterns in neonatal hyperbilirubinemia.

Science.gov (United States)

Gartner, L M; Herrarias, C T; Sebring, R H

1998-01-01

To determine practice patterns of office-based pediatricians and neonatologists in the treatment of neonatal hyperbilirubinemia in healthy, term newborns during 1992, before the publication of the practice guideline for treatment of neonatal jaundice by the American Academy of Pediatrics (AAP). The survey was undertaken to inform the AAP's Subcommittee on Hyperbilirubinemia on current practices and to aid it in its preparation of the guidelines. It was also anticipated that this survey would serve as a basis for comparison for a second survey to be performed several years after the publication of the practice guidelines. A self-administered questionnaire describing a single case of a jaundiced, breastfed 36-hour-old healthy, full-term infant with a total serum bilirubin concentration of 11.0 mg/dL (188 microM/L) was sent to a random sample of 600 office-based pediatricians and 606 neonatologists who were members of the AAP. The final response rate was 74%. Respondents were asked to answer questions regarding treatment of the case based on their actual practices. Ranges of total serum bilirubin concentration were provided as possible answers to questions on initiation of phototherapy and exchange transfusion, and interruption of breastfeeding. Respondents were also queried about frequency of serum bilirubin testing, locations of phototherapy administration, and factors influencing their therapeutic decisions. Four hundred forty-two office-based pediatricians and 444 neonatologists completed the survey. There was a tendency for neonatologists to initiate both phototherapy and exchange transfusions at lower serum bilirubin concentrations than office-based general pediatricians. At a serum bilirubin of 13 to 19 mg/dL (222 to 325 microM/L), 54% of office-based pediatricians stated they would initiate phototherapy whereas 76% of neonatologists would do so. Forty percent of office-based practitioners said they would perform exchange transfusions at serum bilirubin levels

Peculiarities of prolonged neonatal jaundice and possibility of their pharmacological correction

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Yablon O.

2017-03-01

Full Text Available Purpose: to study of peculiarities of prolonged neonatal jaundice and the possibility of pharmacological correction based on ursodeoxycholic acid. Patients and methods. Were examined 42 children (29 boys and 13 girls with prolonged neonatal jaundice. The study group included 22 children, who in complex of pharmacological treatment received the ursodeoxycholic acid, the comparison group comprised 20 children who received only basic treatment such as phototherapy. The effectiveness of the treatment was evaluated by biochemical parameters of blood (bilirubin and its fractions, liver transaminase, the level of serum alpha&fetoprotein, epidermal growth factor were determined by ELISA. Results. All children were full term. The mean age of children in the study group was 20.8±1.9 days in the control group and 22±1.5 days. In the main group indirect bilirubin was above on 35 μmol/l, but significant differences in the level of indirect bilirubin were absent at the beginning of treatment in both groups of children included in the study, respectively, 286±14,3 μmol/l and 250±16.4 μmol/l (p>0.05. The average indirect bilirubin after treatment significantly decreased in both groups but in the main group, a decline of 49% in the comparison group decrease of bilirubin was on 30%. It was also noted signs of neonatal cholestasis: every fifth child had the increased level of direct bilirubin, every third child had elevated liver transaminase. Also, there were no significant differenses in the mean levels of serum AFP and EGF, there were higher in children of both study groups, respectively, mean level of serum AFP in the main group was 834±28 ng/ml in the comparison group — 809±26 ng/ml(p>0.05; mean level of serum EGF in the main group 651±57,2 ng/ml in the comparison group — 714±27 ng/ml(p>0.05. However, in children who were treated with ursodeoxycholic acid (UkrlivR suspension the levels of serum AFP and EGF were significantly decreased, in

Relation Between Interleukin-1-β And Interleukin-8 Levels In Breast Milk (Colostrum) And Neonatal Physiological Jaundice

International Nuclear Information System (INIS)

Mohamed, A.A.; Moawad, A.T.; Marei, E.S.

2011-01-01

The immune system of neonates is influenced by maternal immunity during pregnancy and lactation. Breast-fed neonates have higher incidence of neonatal jaundice and higher level of total serum bilirubin than formula-fed infants. The aim of this study was to find a relationship between neonatal physiological jaundice and interleukin-1-beta (IL-1-β) and interleukin-8 (IL-8) in the colostrum of nursing mothers. Breast milk (colostrum) was collected from 45 nursing mothers of healthy full term neonates. The sharing mothers and their neonates were divided into two groups according to the presence of neonatal jaundice and the level of total serum bilirubin. All jaundiced neonates had total serum bilirubin level more than 12 mg/dl which appeared on the third postpartum day, all of them were breast-fed only. They were subjected to full history through clinical examination and laboratory investigations including determination of colostral levels of IL-1-β and IL-8, by ELISA, and determination of neonatal total serum bilirubin levels. This study revealed that mothers of neonates with physiological jaundice had higher concentrations of IL-1-β and IL-8 in their colostrums as compared with control group. Moreover, it displayed that total serum bilirubin level of jaundiced neonates was higher than its level in non-jaundiced neonates. There were significant correlations between IL- 1-β and IL-8 with mother's age in all groups, while there were inverse correlations between IL-1-β, IL-8 and gestational age of non- jaundiced neonates. Additionally, there was significant correlation between IL-1-β and IL-8 in the colostrum of all mothers enrolled in this study. On the other hand, no correlation was determined between cytokines IL-1-β, IL-8 and total serum bilirubin in all neonates sharing in this study. This study clearly demonstrated that the levels of immunomodulating agents such as cytokines IL-1-β and IL-8 were elevated in the colostrum of mothers with jaundiced neonates

Phototherapy in the newborn: what’s new?

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Murat Yurdakök

2015-10-01

Full Text Available When exposed to light, bilirubin undergoes photoisomerization which are water-soluble and can be excreted in bile and urine. Photoisomerization starts as soon as the lights turned on, and risk of bilirubin encephalopathy is lower in infants who receive phototherapy even in the same serum bilirubin levels. Blue light is absorbed most readily if bilirubin is in a tube, but skin penetration and albumin binding shift of the most effective light to blue-green region. However, there is no consensus on the most effective wavelength for phototherapy. The light sources used in conventional phototherapy are fluorescent bulbs, halogen lamps or light-emitting diodes (LED with equally effective in reducing serum bilirubin levels. Fiberoptic devices are less effective. Despite higher irradiance in double or triple phototherapy, there is no superiority in clinical settings. Hyperthermia and skin rashes are higher when used super (high-intensity LED devices. Watery loose stools may cause dehydration in preterm infants. Riboflavin loss and lipid peroxidation are prevented with using dark tubing or covering the line with aluminum foil. The consequences of light penetration into deep brain in newborn infants because of open wide fontanel and thin skull is unknown. Non-ocular light exposure and suppressed melatonin secretion may affect autonomic and behavioral disturbances. Phototherapy-induced hypocalcemia may be prevented by covering the head. Phototherapy does not effect ductal patency or reopening, its effect on the incidence of retinopathy of prematurity have yielded conflicting results. Neonatal phototherapy increases the risk of asthma and allergic disorders in older age groups. Aggressive (low-threshold phototherapy increase mortality risk in small preterm infants less than 750 g at birth, which may be related to the reduced bilirubin with its antioxidant effects. In conclusion, phototherapy is not a treatment without side effects and overtreatment should

Plasma catecholamine level and portal venous pressure as guides to prognosis in patients with cirrhosis

DEFF Research Database (Denmark)

Tage-Jensen, U; Henriksen, Jens Henrik; Christensen, E

1988-01-01

clinical and biochemical variables and survival. Forty-seven (58%) of the patients died during the follow-up period. Univariate analysis showed that plasma noradrenaline and adrenaline concentrations, portal pressure, indocyanine green clearance, serum sodium, bilirubin, and albumin concentrations......, and the presence of ascites or cardiovascular disease were of significant prognostic value. In a multivariate analysis (Cox regression model), plasma noradrenaline concentration, portal pressure, serum bilirubin concentration, and the presence of ascites and cardiovascular disease remained significant independent...

Hodgkin's lymphoma-related vanishing bile duct syndrome: A case report and literature review

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Kiong-Ming Wong

2013-11-01

Full Text Available We report the case of a 38-year-old man who developed vanishing bile duct syndrome in association with Hodgkin's lymphoma. He was noted to have cervical lymphadenopathy and marked elevation of total serum bilirubin at diagnosis. He achieved complete remission with normalization of serum bilirubin after eight courses of Adriamycin, bleomycin, vinblastine, and dacarbazine chemotherapy followed with autologous hematopoietic cell transplantation. Consecutive liver biopsies performed at diagnosis and at the stage of complete remission revealed the disappearance and regeneration of interlobular bile ducts, respectively. Our case provides pathological evidence that Hodgkin's lymphoma-related vanishing bile duct syndrome is a reversible bile duct injury disease. Bilirubin is a reliable serum marker to monitor the treatment response of these cases. The mechanism to develop hyperbilirubinemia with vanishing bile duct in such a case of Hodgkin's lymphoma remains to be studied. A literature review was carried out.

The clinical pharmacology of technetium diethyl-IDA

International Nuclear Information System (INIS)

Tjen, H.S.L.M.

1979-01-01

In this presentation the performance of the cholescintigraphic study is evaluated from a patho-physiological point of view. With this approach studies of bilirubin metabolism may also provide important information about the mechanisms whereby other organic compounds are transported, metabolized and excreted by the liver cells. The results indicate that diethyl-IDA is a hepatobiliary agent with excellent biological properties. The behaviour of the reagent in normal and pathological individuals can be correlated to bilirubin metabolism. The performance of the cholescintigraphic study is less dependent on the serum bilirubin level in contrast to routinely used radiologic examinations. The level of alkaline phosphatase and serum transaminases is of no influence to the performance of the examination. Combining serial scintigraphy with time-activity curves and functional images from the computer provides additional information so that a differentiation between parenchymal liver disease and bile duct obstruction can be made. (Auth.)

[Treatment of neonatal jaundice by efficient phototherapy].

Science.gov (United States)

Wiese, G

1985-01-01

Idiopathic neonatal jaundice derives from an initial insufficiency of all processes which metabolize hydrophobic bilirubin into diglucuronide excretable in bile. The term 'neonatal hyperbilirubinemia' should only be used when there is a potential risk of bilirubin intoxication. Thus, the concept hyperbilirubinemia is not necessarily linked to the exceeding of a certain threshold value, but rather to the maturity of the child and its clinical condition. In this sense, hyperbilirubinemia is, therefore, always a syndrome requiring treatment. Besides substitution transfusion, which is highly effective per se, but risky and costly, enzyme induction (e.g., by administration of phenobarbital) represents an elegant causal therapy; however, because of its slow onset of action, it has to be given prophylactically to almost all newborns. In addition, this method requires a general induction of all microsomal enzyme systems, and is hence a major intervention in the process of maturation of the neonatal enzyme systems. Therefore, phototherapy must be regarded as the treatment of choice in cases of idiopathic neonatal hyperbilirubinemia. It leads to a bypassing of the hepatic enzyme insufficiency in that by interaction between light with a wavelength of around 460 nm and the bilirubin molecules in the skin, an isomeric, water-soluble, renally secretable bilirubin is produced. The effect of phototherapy, i.e., the reduction in the serum bilirubin concentration under phototherapy, may be described as a simple e-function. The evaluation of this regular occurrence provides important information applicable to the phototherapy procedure: it should not be initiated prematurely, the duration of radiation should be as short as possible, the irradiated surface as large as possible, the radiation source should be exploited to a maximum by keeping the distance from the light source short and using lateral reflectors. As supporting measures intestinal lavage, early oral administration of