Binding of bilirubin and its structural analogues to hepatic microsomal bilirubin UDP glucuronyltransferase

International Nuclear Information System (INIS)

Vanstapel, F.; Blanckaert, N.

1987-01-01

Hepatic glucuronidation of the asymmetrical natural bilirubin molecule results in formation of two different positional isomers, bilirubin C-8 monoglucuronide and bilirubin C-12 monoglucuronide. In view of the existence of multiple isoforms of UDPglucuronyltransferase, which is the microsomal enzyme system responsible for bilirubin esterification, the authors performed kinetic analysis of microsomal glucuronidation of bilirubin and a number of its structural congeners to determine whether synthesis of the two monoglucuronide isomers involved two distinct substrate-binding sites or reflected two different modes of binding to a single catalytic site. Both isomers were found in all tested species (man, rat, guinea pig, sheep), but there were marked species differences in the C-8/C-12 ratio of monoglucuronide found in bile or formed by liver microsomes. Correspondence between in vivo and in vitro results for such regioselectivity of glucuronidation was excellent in each species. On the basis of these results of kinetic analysis of bilirubin esterification at variable pigment substrate concentrations and inhibition studies with alternative substrates, the authors postulate that both natural monoglucuronide isomers are synthesized at a single binding site. Possible mechanisms responsible for the markedly regioselective esterification of bilirubin by rat and sheep liver were investigated by study of glucuronidation of selected structural analgoues of the pigment. Collectively, their findings suggest that the molecular from(s) of bilirubin able to engage in catalytically effective binding to UDPglucuronyltransferase does (do) not correspond with intramolecularly hydrogen-bonded conformers and that the nature of the β-substituents of the outer pyrromethenone rings is a key determinant of glucuronidation rate

Biology of Bilirubin Photoisomers.

Science.gov (United States)

Hansen, Thor Willy Ruud

2016-06-01

Phototherapy is the main treatment for neonatal hyperbilirubinemia. In acute treatment of extreme hyperbilirubinemia, intensive phototherapy may have a role in 'detoxifying' the bilirubin molecule to more polar photoisomers, which should be less prone to crossing the blood-brain barrier, providing a 'brain-sparing' effect. This article reviews the biology of bilirubin isomers. Although there is evidence supporting the lower toxicity of bilirubin photoisomers, there are studies showing the opposite. There are methodologic weaknesses in most studies and better-designed experiments are needed. In an infant acutely threatened by bilirubin-induced brain damage, intensified phototherapy should be used expediently and aggressively. Copyright © 2016 Elsevier Inc. All rights reserved.

Bilirubin present in diverse angiosperms.

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

2010-01-01

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

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

Directory of Open Access Journals (Sweden)

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

Newborn Bilirubin Screening for Preventing Severe Hyperbilirubinemia and Bilirubin Encephalopathy: A Rapid Review.

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Bhardwaj, Kalpana; Locke, Tiffany; Biringer, Anne; Booth, Allyson; Darling, Elizabeth K; Dougan, Shelley; Harrison, Jane; Hill, Stephen; Johnson, Ana; Makin, Susan; Potter, Beth; Lacaze-Masmonteil, Thierry; Little, Julian

2017-01-01

According to the 2004 American Academy of Pediatrics guideline on the management of hyperbilirubinemia, every newborn should be assessed for the risk of developing severe hyperbilirubinemia with the help of predischarge total serum bilirubin or transcutaneous bilirubin measurements and/or assessments of clinical risk factors. The aim of this rapid review is 1) to review the evidence for 1) predicting and preventing severe hyperbilirubinemia and bilirubin encephalopathy, 2) determining the efficacy of home/community treatments (home phototherapy) in the prevention of severe hyperbilirubinemia, and 3) non-invasive/transcutaneous methods for estimating serum bilirubin level. In this rapid review, studies were identified through the Medline database. The main outcomes of interest were severe hyperbilirubinemia and encephalopathy. A subset of articles was double screened and all articles were critically appraised using the SIGN and AMSTAR checklists. This review investigated if systems approach is likely to reduce the occurrence of severe hyperbilirubinemia. Fifty-two studies met the inclusion criteria. Included studies assessed the association between bilirubin measurement early in neonatal life and the subsequent development of severe hyperbilirubinemia and chronic bilirubin encephalopathy/kernicterus. It was observed that, highest priority should be given to (i) universal bilirubin screening programs; (ii) implementation of community and midwife practice; (iii) outreach to communities for education of prospective parents; and (iv) development of clinical pathways to monitor, evaluate and track infants with severe hyperbilirubinemia. We found substantial observational evidence that severe hyperbilirubinemia can be accurately predicted and prevented through universal bilirubin screening. So far, there is no evidence of any harm. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Photoacoustic microscopy of bilirubin in tissue phantoms

Science.gov (United States)

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

2012-12-01

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

Bilirubin Binding Capacity in the Preterm Neonate.

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Amin, Sanjiv B

2016-06-01

Total serum/plasma bilirubin (TB), the biochemical measure currently used to evaluate and manage hyperbilirubinemia, is not a useful predictor of bilirubin-induced neurotoxicity in premature infants. Altered bilirubin-albumin binding in premature infants limits the usefulness of TB in premature infants. In this article, bilirubin-albumin binding, a modifying factor for bilirubin-induced neurotoxicity, in premature infants is reviewed. Copyright © 2016 Elsevier Inc. All rights reserved.

Quantitative imaging of bilirubin by photoacoustic microscopy

Science.gov (United States)

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

2013-03-01

Noninvasive detection of both bilirubin concentration and its distribution is important for disease diagnosis. Here we implemented photoacoustic microscopy (PAM) to detect bilirubin distribution. We first demonstrate that our PAM system can measure the absorption spectra of bilirubin and blood. We also image bilirubin distributions in tissuemimicking samples, both without and with blood mixed. Our results show that PAM has the potential to quantitatively image bilirubin in vivo for clinical applications.

Bilirubin Binding to PPARα Inhibits Lipid Accumulation

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

2016-01-01

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

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

Science.gov (United States)

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

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.

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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.

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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.

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

Science.gov (United States)

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

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

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... 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.

Extra-osseous uterine pathophysiology demonstrated on skeletal scintigraphy

International Nuclear Information System (INIS)

Mansberg, R.; Lewis, G.

1999-01-01

Full text: Skeletal scintigraphy is a sensitive procedure for evaluating disease and trauma involving the skeleton. Extra-skeletal pathophysiology is also often demonstrated. This may include uptake by tumours, soft tissue calcification and infection as well as renal pathology. Skeletal scintigraphy is often performed to evaluate hip and back pain and extra-osseous uterine pathophysiology can be demonstrated in both the early and late phases of the study as in the following cases. Three women underwent skeletal scintigraphy for the investigation of low back pain in two patients and post-partum hip pain in one. A large vascular uterus with deviation of the bladder was demonstrated in the post-partum patient. Increased pelvic vascularity and bladder deviation in the second patient was shown by ultrasound to correspond to a left-sided fibroid with associated adenomyosis. In the third case, right-sided pelvic vascularity and left bladder deviation were shown on ultrasound to be due to an anteverted, anteflexed uterus tilted to the right. These cases illustrate the importance of documenting extra-osseous findings on skeletal scintigraphy and the benefits of correlation with anatomical imaging

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

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.

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.

Science.gov (United States)

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

Science.gov (United States)

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

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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

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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.

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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

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.

Influence of hemoglobin on non-invasive optical bilirubin sensing

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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

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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?

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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

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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.

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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

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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.

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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.

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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.

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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.

Science.gov (United States)

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.

Science.gov (United States)

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

Directory of Open Access Journals (Sweden)

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.

Science.gov (United States)

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.

Science.gov (United States)

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.

Bioprinting for vascular and vascularized tissue biofabrication.

Science.gov (United States)

Datta, Pallab; Ayan, Bugra; Ozbolat, Ibrahim T

2017-03-15

Bioprinting is a promising technology to fabricate design-specific tissue constructs due to its ability to create complex, heterocellular structures with anatomical precision. Bioprinting enables the deposition of various biologics including growth factors, cells, genes, neo-tissues and extra-cellular matrix-like hydrogels. Benefits of bioprinting have started to make a mark in the fields of tissue engineering, regenerative medicine and pharmaceutics. Specifically, in the field of tissue engineering, the creation of vascularized tissue constructs has remained a principal challenge till date. However, given the myriad advantages over other biofabrication methods, it becomes organic to expect that bioprinting can provide a viable solution for the vascularization problem, and facilitate the clinical translation of tissue engineered constructs. This article provides a comprehensive account of bioprinting of vascular and vascularized tissue constructs. The review is structured as introducing the scope of bioprinting in tissue engineering applications, key vascular anatomical features and then a thorough coverage of 3D bioprinting using extrusion-, droplet- and laser-based bioprinting for fabrication of vascular tissue constructs. The review then provides the reader with the use of bioprinting for obtaining thick vascularized tissues using sacrificial bioink materials. Current challenges are discussed, a comparative evaluation of different bioprinting modalities is presented and future prospects are provided to the reader. Biofabrication of living tissues and organs at the clinically-relevant volumes vitally depends on the integration of vascular network. Despite the great progress in traditional biofabrication approaches, building perfusable hierarchical vascular network is a major challenge. Bioprinting is an emerging technology to fabricate design-specific tissue constructs due to its ability to create complex, heterocellular structures with anatomical precision

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.

Science.gov (United States)

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.

Science.gov (United States)

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.

Influence of Fasciola Hepatica on Serum Biochemical Parameters and Vascular and Biliary System of Sheep Liver

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A Hodžić

2013-03-01

Full Text Available Background: The aim of this study was to evaluate the functional capacity of the liver based on the activity of specific enzymes and bilirubin in serum and also to investigate the influence of mechanical and toxic effects of Fasciola hepatica on the structures of the blood vessels and biliary tract in the sheep liver.Methods: Blood samples and liver of 63 indigenous sheep of Pramenka breed, slaughtered in the period from March to December 2009 were used. Based on parasitological findings in the liver, all animals were divided into two groups: control (n=34 and infected group (n=29. For investigation and description of pathological changes in sheep liver, naturally infected with F. hepatica, corrosion cast technique was used.Results: Biochemical analysis of tested parameters showed a significant elevation (P≤0.05 of serum gamma-glutamyl transferase (GGT, total bilirubin (TBIL and direct bilirubin (DBIL in infected sheep group comparing with the control group. No significant differences were observed for activity of aspartate aminotranferase (AST between groups. Vascular and biliary systems of the liver were found to be affected.Conclusion: Results of biochemical analysis are consistent with pathological findings and measuring of tested parameters could be used in early diagnosis of sheep fasciolosis and to test the effectiveness of anthelmintic therapy. Corrosion cast technique is very useful for investigation of pathological changes and neoangiogenesis of vascular and biliary system in sheep liver, caused by mechanical and toxic effects of F. hepatica.

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.

Vascular plugs - A key companion to Interventionists - 'Just Plug it'.

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Ramakrishnan, Sivasubramanian

2015-01-01

Vascular plugs are ideally suited to close extra-cardiac, high flowing vascular communications. The family of vascular plugs has expanded. Vascular plugs in general have a lower profile and the newer variants can be delivered even through a diagnostic catheter. These features make them versatile and easy to use. The Amplatzer vascular plugs are also used for closing intracardiac defects including coronary arterio-venous fistula and paravalvular leakage in an off-label fashion. In this review, the features of currently available vascular plugs are reviewed along with tips and tricks of using them in the cardiac catheterization laboratory. Copyright © 2015. Published by Elsevier B.V.

Pictorial essay: Vascular interventions in extra cranial head and neck

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Suyash S Kulkarni; Nitin S Shetty; Tejas P Dharia; Ashwin M Polnaya

2012-01-01

Medicine is an ever changing field and interventional radiology (IR) procedures are becoming increasingly popular because of high efficacy and its minimally invasive nature of the procedure. Management of disease processes in the extra cranial head and neck (ECHN) has always been a challenge due to the complex anatomy of the region. Cross sectional imaging of the ECHN has grown and evolved tremendously and occupies a pivotal and integral position in the clinical management of variety of head ...

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

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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.

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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

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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...

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.

Science.gov (United States)

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.

Science.gov (United States)

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

Directory of Open Access Journals (Sweden)

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.

Science.gov (United States)

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.

Science.gov (United States)

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.

Science.gov (United States)

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

Directory of Open Access Journals (Sweden)

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.

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.

Science.gov (United States)

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

Exposure of chick embryos to cadmium changes the extra-embryonic vascular branching pattern and alters expression of VEGF-A and VEGF-R2

Energy Technology Data Exchange (ETDEWEB)

Gheorghescu, Anna Kaskova [School of Medicine and Medical Science, University College Dublin, Belfield, Dublin 4 (Ireland); Tywoniuk, Bartlomiej [School of Physics, University College Dublin, Belfield, Dublin 4 (Ireland); Complex and Adaptive Systems Laboratory, University College Dublin, Belfield, Dublin 4 (Ireland); Duess, Johannes [School of Medicine and Medical Science, University College Dublin, Belfield, Dublin 4 (Ireland); National Children' s Research Centre, Our Lady' s Children' s Hospital, Crumlin, Dublin 12 (Ireland); Buchete, Nicolae-Viorel, E-mail: buchete@ucd.ie [School of Physics, University College Dublin, Belfield, Dublin 4 (Ireland); Complex and Adaptive Systems Laboratory, University College Dublin, Belfield, Dublin 4 (Ireland); Thompson, Jennifer, E-mail: jennifer.thompson@ucd.ie [School of Medicine and Medical Science, University College Dublin, Belfield, Dublin 4 (Ireland)

2015-11-15

Cadmium (Cd) has several industrial applications, and is found in tobacco products, a notable source of human exposure. Vascular endothelial cells are key targets of Cd toxicity. Here, we aim to quantify the alteration to vascular branching pattern following Cd exposure in the chick extra-embryonic membrane (EEM) using fractal analysis, and explore molecular cues to angiogenesis such as VEGF-A and VEGF-R2 expression following Cd treatment. Chicken embryos were incubated for 60 h to Hamburger–Hamilton developmental stage 16–17, then explanted and treated with 50 μL of 50 μmol cadmium acetate (CdAc) or an equivalent volume of equimolar sodium acetate (NaAc). Images of embryos and their area vasculosa (AV) were captured and analyzed at 4 different time points (4, 8, 24 and 48 h) following treatment. Vascular branching in the AV was quantified using its fractal dimension (D{sub f}), estimated using a box counting method. Gallinaceous VEGF ELISA was used to measure the VEGF-A concentration in the EEM following treatment, with determination of the relative expression of VEGF-A and VEGF-R2 using quantitative real-time RT-PCR. Vascular branching increased monotonically in the control group at all time points. The anti-angiogenic effect of Cd exposure on the AV was reflected by a significant reduction in D{sub f} when compared with controls. D{sub f} was more markedly reduced in cultures with abnormal embryos. The expression of VEGF-A protein, and VEGF-A and VEGF-R2 mRNA were reduced in Cd-exposed EEMs. Both molecules contribute to growth, vessel sprouting and branching processes, which supports our findings using fractal analysis. - Highlights: • The chick area vasculosa was undersized in embryos exposed to 50 μM cadmium acetate. • Fractal dimension was reduced in the AV after Cd exposure, indicating decreased branching. • VEGF-A protein was decreased in Cd-treated extraembryonic membranes. • VEGF-A and VEGF-R2 mRNA was decreased in Cd-treated extraembryonic

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

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

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.

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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.

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

International Nuclear Information System (INIS)

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

Science.gov (United States)

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

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?

Science.gov (United States)

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.

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.

Nonalcoholic fatty liver disease and chronic vascular complications of diabetes mellitus.

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Targher, Giovanni; Lonardo, Amedeo; Byrne, Christopher D

2018-02-01

Nonalcoholic fatty liver disease (NAFLD) and diabetes mellitus are common diseases that often coexist and might act synergistically to increase the risk of hepatic and extra-hepatic clinical outcomes. NAFLD affects up to 70-80% of patients with type 2 diabetes mellitus and up to 30-40% of adults with type 1 diabetes mellitus. The coexistence of NAFLD and diabetes mellitus increases the risk of developing not only the more severe forms of NAFLD but also chronic vascular complications of diabetes mellitus. Indeed, substantial evidence links NAFLD with an increased risk of developing cardiovascular disease and other cardiac and arrhythmic complications in patients with type 1 diabetes mellitus or type 2 diabetes mellitus. NAFLD is also associated with an increased risk of developing microvascular diabetic complications, especially chronic kidney disease. This Review focuses on the strong association between NAFLD and the risk of chronic vascular complications in patients with type 1 diabetes mellitus or type 2 diabetes mellitus, thereby promoting an increased awareness of the extra-hepatic implications of this increasingly prevalent and burdensome liver disease. We also discuss the putative underlying mechanisms by which NAFLD contributes to vascular diseases, as well as the emerging role of changes in the gut microbiota (dysbiosis) in the pathogenesis of NAFLD and associated vascular diseases.

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)

International Nuclear Information System (INIS)

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.

EXTraS: Exploring the X-ray Transient and variable Sky

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De Luca, A.; Salvaterra, R.; Tiengo, A.; D'Agostino, D.; Watson, M.; Haberl, F.; Wilms, J.

2017-10-01

The EXTraS project extracted all temporal domain information buried in the whole database collected by the EPIC cameras onboard the XMM-Newton mission. This included a search and characterisation of variability, both periodic and aperiodic, in hundreds of thousands of sources spanning more than eight orders of magnitude in time scale and six orders of magnitude in flux, as well as a search for fast transients, missed by standard image analysis. Phenomenological classification of variable sources, based on X-ray and multiwavelength information, has also been performed. All results and products of EXTraS are made available to the scientific community through a web public data archive. A dedicated science gateway will allow scientists to apply EXTraS pipelines on new observations. EXTraS is the most comprehensive analysis of variability, on the largest ever sample of soft X-ray sources. The resulting archive and tools disclose an enormous scientific discovery space to the community, with applications ranging from the search for rare events to population studies, with impact on the study of virtually all astrophysical source classes. EXTraS, funded within the EU/FP7 framework, is carried out by a collaboration including INAF (Italy), IUSS (Italy), CNR/IMATI (Italy), University of Leicester (UK), MPE (Germany) and ECAP (Germany).

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

Science.gov (United States)

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.

Science.gov (United States)

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.

Science.gov (United States)

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.

Science.gov (United States)

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.

Science.gov (United States)

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.

Science.gov (United States)

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

Science.gov (United States)

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

Energy Technology Data Exchange (ETDEWEB)

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.

Neuroprotection against vascular dementia after acupuncture combined with donepezil hydrochloride: P300 event related potential

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Qiang Liu

2016-01-01

Full Text Available Acupuncture can be used to treat various nervous system diseases. Here, 168 vascular dementia patients were orally administered donepezil hydrochloride alone (5 mg/day, once a day for 56 days, or combined with acupuncture at Shenting (DU24, Tianzhu (BL10, Sishencong (Extra, Yintang (Extra, Renzhong (DU26, Neiguan (PC6, Shenmen (HT7, Fengchi (GB20, Wangu (GB12 and Baihui (DU20 (once a day for 56 days. Compared with donepezil hydrochloride alone, P300 event related potential latency was shorter with an increased amplitude in patients treated with donepezil hydrochloride and acupuncture. Mini-Mental State Examination score was also higher. Moreover, these differences in P300 latency were identified within different infarcted regions in patients treated with donepezil hydrochloride and acupuncture. These findings indicate that acupuncture combined with donepezil hydrochloride noticeably improves cognitive function in patients with vascular dementia, and exerts neuroprotective effects against vascular dementia.

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

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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.

Science.gov (United States)

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.

Science.gov (United States)

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

Science.gov (United States)

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.

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.

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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

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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

Bile pigments in pulmonary and vascular disease

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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.

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

Robotic surgery twice performed in the treatment of hilar cholangiocarcinoma with deep jaundice: delayed right hemihepatectomy following the right-hepatic vascular control.

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Zhu, Zhenyu; Liu, Quanda; Chen, Junzhou; Duan, Weihong; Dong, Maosheng; Mu, Peiyuan; Cheng, Di; Che, Honglei; Zhang, Tao; Xu, Xiaoya; Zhou, Ningxin

2014-10-01

To explore and find a new method to treat hilar cholangiocarcinoma with deep jaundice assisted by Da Vinci robot. A hilar cholangiocarcinoma patient of type Bismuch-Corlette IIIa was found with deep jaundice (total bilirubin: 635 µmol/L). On the first admission, we performed Da Vinci robotic surgery including drainage of left hepatic duct, dissection of right hepatic vessels (right portal vein and right hepatic artery), and placement of right-hepatic vascular control device. Three weeks later on the second admission when the jaundice disappeared we occluded right-hepatic vascular discontinuously for 6 days and then sustained later. On the third admission after 3 weeks of right-hepatic vascular control, the right hemihepatectomy was performed by Da Vinci robot for the second time. The future liver remnant after the right-hepatic vascular control increased from 35% to 47%. The volume of left lobe increased by 368 mL. When the total bilirubin and liver function were all normal, right hemihepatectomy was performed by Da Vinci robot 10 weeks after the first operation. The removal of atrophic right hepatic lobe with tumor in bile duct was found with no pathologic cancer remaining in the margin. The patient was followed up at our outpatient clinic every 3 months and no tumor recurrence occurs by now (1 y). Under the Da Vinci robotic surgical system, a programmed treatment can be achieved: first, the hepatic vessels were controlled gradually together with biliary drainage, which results in liver's partial atrophy and compensatory hypertrophy in the other part. Then a radical hepatectomy could be achieved. Such programmed hepatectomy provides a new treatment for patients of hilar cholangiocarcinoma with deep jaundice who have the possibility of radical heptolobectomy.

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

Anastomose arterial extra-intracraniana para tratamento de paciente com isquemia cerebral refratária ao manejo clínico

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Falavigna Asdrubal

2004-01-01

Full Text Available A anastomose extra-intracraniana pode ser utilizada em casos selecionados de insuficiência vascular encefálica refratária ao tratamento clínico. Descrevemos um caso de isquemia encefálica em território de artéria cerebral média direita devida à oclusão da artéria carótida interna homolateral com conseqüente redução da perfusão e reserva vascular nos hemisférios frontal e parietal. Apesar do tratamento clínico, a melhora do déficit motor estava relacionada diretamente com a manutenção de níveis tensionais sistêmicos elevados pelo uso de vasopressor. Após anastomose extra-intracraniana término-lateral entre as artérias temporal superficial e cerebral média direita, houve melhora significativa da perfusão cerebral com remissão do déficit motor.

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.

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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

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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

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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

Extra-Nasopharyngeal Angiofibroma in a Pre-Pubertal Child

Directory of Open Access Journals (Sweden)

Subhro Ganguly

2017-10-01

Full Text Available Nasopharyngeal Angiofibromas (NA are benign fibro-vascular tumours, predominantly occurring in the region around sphenopalatine foramen of adolescent males. Angiofibromas arising outside nasopharynx are termed as Extra-Nasopharyngeal Angiofibromas (ENA which often gets misdiagnosed because of its rarity and atypical clinical and biological behaviour. We present a case of angiofibroma of nasal septum in a seven-year-old boy presenting with two months history of left nasal obstruction and occasional nasal bleeding. CECT revealed a contrast enhanced soft tissue mass in left nasal cavity with no extension into the sinuses and nasopharynx. The mass was completely removed by lateral rhinotomy approach and a follow up of ten months showed no recurrence. Histopathology and immunohistochemistry confirmed the diagnosis of angiofibroma. The age of the patient and the location of the tumour make the case exceptionally rare. We conclude that ENA must be taken into consideration in differential diagnosis of unilateral vascular nasal mass, and nasal septum should be taken into account as a potential, yet exceptional site for the tumour. Furthermore the age and gender of the patient should not be given utmost importance for diagnosis of angiofibromas.

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.

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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.

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...

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.

The pathology and pathophysiology of vascular dementia.

Science.gov (United States)

Kalaria, Raj N

2017-12-19

Vascular dementia (VaD) is widely recognised as the second most common type of dementia. Consensus and accurate diagnosis of clinically suspected VaD relies on wide-ranging clinical, neuropsychological and neuroimaging measures in life but more importantly pathological confirmation. Factors defining subtypes of VaD include the nature and extent of vascular pathologies, degree of involvement of extra and intracranial vessels and the anatomical location of tissue changes as well as time after the initial vascular event. Atherosclerotic and cardioembolic diseases combined appear the most common subtypes of vascular brain injury. In recent years, cerebral small vessel disease (SVD) has gained prominence worldwide as an important substrate of cognitive impairment. SVD is characterised by arteriolosclerosis, lacunar infarcts and cortical and subcortical microinfarcts and diffuse white matter changes, which involve myelin loss and axonal abnormalities. Global brain atrophy and focal degeneration of the cerebrum including medial temporal lobe atrophy are also features of VaD similar to Alzheimer's disease. Hereditary arteriopathies have provided insights into the mechanisms of dementia particularly how arteriolosclerosis, a major contributor of SVD promotes cognitive impairment. Recently developed and validated neuropathology guidelines indicated that the best predictors of vascular cognitive impairment were small or lacunar infarcts, microinfarcts, perivascular space dilation, myelin loss, arteriolosclerosis and leptomeningeal cerebral amyloid angiopathy. While these substrates do not suggest high specificity, VaD is likely defined by key neuronal and dendro-synaptic changes resulting in executive dysfunction and related cognitive deficits. Greater understanding of the molecular pathology is needed to clearly define microvascular disease and vascular substrates of dementia. Copyright © 2017 Elsevier Ltd. All rights reserved.

Repair of bile duct injuries with Gore-Tex vascular grafts: experimental study in dogs.

Science.gov (United States)

Gómez, Néstor A; Alvarez, Ludwig R; Mite, Alfredo; Andrade, Jean P; Alvarez, José R; Vargas, Paola E; Tomalá, Nancy E; Vivas, Alex F; Zapatier, Jorge A

2002-01-01

Bile duct injury is the most feared complication related to biliary tract operations. The goal of this investigation was to offer an alternative treatment that might prevent this complication. Twelve mongrel dogs, thin-walled FEP-ringed Gore-Tex vascular grafts, and Gore-Tex sutures were used in this study. The dogs were randomized into three groups of four according to the length of time of graft implantation: group 1 = 1 month; group 2 = 2 months; and group 3 = 3 months. During the first part of the study, a biliary injury was induced by ligating the middle choledocus after performing a conventional cholecystectomy. During the second part of the study, biliodigestive and biliobiliary anastomosis were performed using Gore-Tex vascular grafts prior to resection of the stenotic area. Initially, an increase in serum bilirubin and alkaline phosphatase levels was noted. Two weeks later, after implantation of the grafts, these values returned to normal. Thin-walled FEP-ringed Gore-Tex vascular grafts were found to be useful in the repair of bile duct injuries, especially in complete transections of the common bile duct. The ductility and flexibility of the material allows any type of anastomosis to be performed, especially when bile duct-gut anastomosis is technically difficult.

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

Experimental comparison study of the tissue characteristics in transjugular intrahepatic portosystemic shunt and vascular stent

International Nuclear Information System (INIS)

Lu Qin; An Yanli; Deng Gang; Fang Wen; Zhu Guangyu; Niu Huanzhang; Yu Hui; Li Guozhao; Teng Gaojun; Wang Zhen; Wei Xiaoying

2009-01-01

Objective: To investigate the tissue characteristics within vascular stent and transjugular intrahepatic portosystemic shunt(TIPS) on swine and to provide more information for the understanding and prevention of vascular stent and TIPS restenosis. Methods: Animal models for TIPS were built in 6 swine and vascular stents were implanted in iliac veins simultaneously. 14-28 days after the operation, the 6 swine were killed to remove the TIPS and vascular stent and the pathological examinations were performed on the tissues within the shunt and stent. The similarities and differences of the tissues within the shunt and stent were analyzed with Krttskal Wallis test. Results: Restenosis of TIPS occurred in 4 models and complete occlusion were seen in 2, while all vascular stents were patent and coated with a thin layer of intimal tissue. Electron microscopic results showed that the tissues in restenotic TIPS were loose and with more extra matrix and fibers, and less smooth muscle, fibroblastic and myofibroblastic cells with different and irregular shape and rich secretory granules. The tissues in patent TIPS contained more extra fibers, smooth muscle and fibroblastic cells with normal organelle. The intimal tissues in vascular stent contained more fibers and fibroblasts cells, less smooth muscle cells. On immunohistochemical staining, the tissues in restenotic and patent TIPS as well as the intimal tissues in vascular stent had strong positive expression for anti-SMC- actin-α, the expression were gradually weakened for PCNA, the intimal tissues in vascular stent had a strong positive expression for vimentin, while the expression of the tissues in restenotic and patent TIPS were weakened gradually. For myoglobulin, the tissues in restenotic TIPS had weakly positive expression, the expression in patent TIPS and vascular stent were almost negative. Western blot results for TGF-β showed that the absorbance ratios of the intima tissues in vascular stent, normal vascular

Investigation of the extra-extra-push by pre-scission neutron measurements with DEMON

International Nuclear Information System (INIS)

Rudolf, Gerard

1998-01-01

The objective of this talk is to present a simple method to calculate pre- and post-scission neutron multiplicities in the frame of the Bass model. This method is of particular interest for very heavy systems for which an extra-extra-push is supposed to hinder fusion. The multiplicities calculated by the model are compared to published data covering a broad range of projectile and target masses, and to more recent ones obtained with the help of the Demon detector and addressing specifically the existence of the extra-extra-push

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

Directory of Open Access Journals (Sweden)

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.

Diagnosing antiphospholipid syndrome: 'extra-criteria' manifestations and technical advances.

Science.gov (United States)

Sciascia, Savino; Amigo, Mary-Carmen; Roccatello, Dario; Khamashta, Munther

2017-09-01

First described in the early 1980s, antiphospholipid syndrome (APS) is a unique form of acquired autoimmune thrombophilia in which patients present with clinical features of recurrent thrombosis and pregnancy morbidity and persistently test positive for the presence of antiphospholipid antibodies (aPL). At least one clinical (vascular thrombosis or pregnancy morbidity) and one lab-based (positive test result for lupus anticoagulant, anticardiolipin antibodies and/or anti-β2-glycoprotein 1 antibodies) criterion have to be met for a patient to be classified as having APS. However, the clinical spectrum of APS encompasses additional manifestations that can affect many organs and cannot be explained exclusively by patients being in a prothrombotic state; clinical manifestations not listed in the classification criteria (known as extra-criteria manifestations) include neurologic manifestations (chorea, myelitis and migraine), haematologic manifestations (thrombocytopenia and haemolytic anaemia), livedo reticularis, nephropathy and valvular heart disease. Increasingly, research interest has focused on the development of novel assays that might be more specific for APS than the current aPL tests. This Review focuses on the current classification criteria for APS, presenting the role of extra-criteria manifestations and lab-based tests. Diagnostic approaches to difficult cases, including so-called seronegative APS, are also discussed.

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.

Inhomogeneous compact extra dimensions

Energy Technology Data Exchange (ETDEWEB)

Bronnikov, K.A. [Center of Gravity and Fundamental Metrology, VNIIMS, 46 Ozyornaya st., Moscow 119361 (Russian Federation); Budaev, R.I.; Grobov, A.V.; Dmitriev, A.E.; Rubin, Sergey G., E-mail: kb20@yandex.ru, E-mail: buday48@mail.ru, E-mail: alexey.grobov@gmail.com, E-mail: alexdintras@mail.ru, E-mail: sergeirubin@list.ru [National Research Nuclear University MEPhI (Moscow Engineering Physics Institute), 115409 Moscow (Russian Federation)

2017-10-01

We show that an inhomogeneous compact extra space possesses two necessary features— their existence does not contradict the observable value of the cosmological constant Λ{sub 4} in pure f ( R ) theory, and the extra dimensions are stable relative to the 'radion mode' of perturbations, the only mode considered. For a two-dimensional extra space, both analytical and numerical solutions for the metric are found, able to provide a zero or arbitrarily small Λ{sub 4}. A no-go theorem has also been proved, that maximally symmetric compact extra spaces are inconsistent with 4D Minkowski space in the framework of pure f ( R ) gravity.

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

Directory of Open Access Journals (Sweden)

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

EXTRA LIFE

Directory of Open Access Journals (Sweden)

Ruth S. Contreras Espinosa

2016-02-01

Full Text Available El creciente número de personas jugando videojuegos significa que estos están teniendo un efecto innegable sobre nuestra cultura. Este efecto es claramente visible en una aceptación general. Los videojuegos también han cambiado la forma en que muchas otras formas de medios de comunicación, se producen y consumen. Los videojuegos tienen una influencia creciente en nuestra cultura, y en "EXTRA LIFE" diferentes autores expresan sus opiniones sobre este nuevo medio. EXTRA LIFE Abstract The increasing number of people playing video games means that they are having an undeniable effect on culture. This effect is clearly visible in the increasing mainstream acceptance of aspects of gaming culture. Video games have also changed the way that many other forms of media, are produced and consumed. Video games have an increasing influence on our culture,  and in "EXTRA LIFE" diferent authors have voiced their opinions on this new media. Keywords: Video games; culture; effects; games.

Trend, Risk Factors, and Costs of Clostridium difficile Infections in Vascular Surgery.

Science.gov (United States)

Egorova, Natalia N; Siracuse, Jeffrey J; McKinsey, James F; Nowygrod, Roman

2015-01-01

Starting in December 2013, the Hospital Inpatient Quality Reporting Program included Clostridium difficile infection (CDI) rates as a new publically reported quality measure. Our goal was to review the trend, hospital variability in CDI rates, and associated risk factors and costs in vascular surgery. The rates of CDI after major vascular procedures including aortic abdominal aneurysm (AAA) repair, carotid endarterectomy or stenting, lower extremity revascularization (LER), and LE amputation were identified using Nationwide Inpatient Sample database for 2000-2011. Risk factors associated with CDI were analyzed with hierarchical multivariate logistic regression. Extra costs, length of stay (LOS), and mortality were assessed for propensity-matched hospitalizations with and without CDI. During the study period, the rates of CDI after vascular procedures had increased by 74% from 0.6 in 2000 to 1.05% in 2011, whereas the case fatality rate was stable at 9-11%. In 2011, the highest rates were after ruptured aortic abdominal aneurysm (rAAA) repair (3.3%), followed by lower extremity amputations (2.3%) and elective open AAA (1.3%). The rates of CDI increased after all vascular procedures during the 12 years. The highest increase was after endovascular LER (151.8%) and open rAAA repair (135.7%). In 2011, patients who had experienced CDI had median LOS of 15 days (interquartile range, 9-25 days) compared with 8.3 days for matched patients without CDI, in-hospital mortality 9.1% (compared with 5.0%), and $13,471 extra cost per hospitalization. The estimated cost associated with CDI in vascular surgery in the United States was ∼$98 million in 2011. Hospital rates of CDI varied from 0 to 50% with 3.5% of hospitals having infection rates ≥5%. Factors associated with CDI included multiple chronic conditions, female gender, surgery type, emergent and weekend hospitalizations, hospital transfers, and urban locations. Despite potential reduction of infection rates as evidenced

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.

Tendinopathy of the long head of the biceps tendon: histopathologic analysis of the extra-articular biceps tendon and tenosynovium.

Science.gov (United States)

Streit, Jonathan J; Shishani, Yousef; Rodgers, Mark; Gobezie, Reuben

2015-01-01

Bicipital tendinitis is a common cause of anterior shoulder pain, but there is no evidence that acute inflammation of the extra-articular long head of the biceps (LHB) tendon is the root cause of this condition. We evaluated the histologic findings of the extra-articular portion of the LHB tendon and synovial sheath in order to compare those findings to known histologic changes seen in other tendinopathies. Twenty-six consecutive patients (mean age 45.4±13.7 years) underwent an open subpectoral biceps tenodesis for anterior shoulder pain localized to the bicipital groove. Excised tendons were sent for histologic analysis. Specimens were graded using a semiquantitative scoring system to evaluate tenocyte morphology, the presence of ground substance, collagen bundle characteristics, and vascular changes. Chronic inflammation was noted in only two of 26 specimens, and no specimen demonstrated acute inflammation. Tenocyte enlargement and proliferation, characterized by increased roundness and size of the cell and nucleus with proteoglycan matrix expansion and myxoid degenerative changes, was found in all 26 specimens. Abundant ground substance, collagen bundle changes, and increased vascularization were visualized in all samples. Anterior shoulder pain attributed to the biceps tendon does not appear to be due to an inflammatory process in most cases. The histologic findings of the extra-articular portion of the LHB tendon and synovial sheath are similar to the pathologic findings in de Quervain tenosynovitis at the wrist, and may be due to a chronic degenerative process similar to this and other tendinopathies of the body.

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

Directory of Open Access Journals (Sweden)

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

Directory of Open Access Journals (Sweden)

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.

An introduction to extra dimensions

International Nuclear Information System (INIS)

Perez-Lorenzana, Abdel

2005-01-01

Models that involve extra dimensions have introduced completely new ways of looking up on old problems in theoretical physics. The aim of the present notes is to provide a brief introduction to the many uses that extra dimensions have found over the last few years, mainly following an effective field theory point of view. Most parts of the discussion are devoted to models with flat extra dimensions, covering both theoretical and phenomenological aspects. We also discuss some of the new ideas for model building where extra dimensions may play a role, including symmetry breaking by diverse new and old mechanisms. Some interesting applications of these ideas are discussed over the notes, including models for neutrino masses and proton stability. The last part of this review addresses some aspects of warped extra dimensions, and graviton localization

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.

Coexistence of pheochromocytoma with uncommon vascular lesions

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Sunil Kumar Kota

2012-01-01

Full Text Available Background: Pheochromocytoma/paragangliomas have been described to be associated with rare vascular abnormalities like renal artery stenosis. Coexistence of physiologically significant renal artery lesions is a compounding factor that alters management and prognosis of pheochromocytoma patients. Apart from individual case reports, data on such association in Indian population is not available. The aim of this study is to find the nature and prevalence of associated vascular abnormalities. Materials and Methods: From 1990 to 2010, a total of 50 patients were diagnosed with pheochromocytoma/paragangliomas. Hospital charts of these patients were reviewed retrospectively to identify those with unusual vascular abnormalities. Available literature was also reviewed. Results: Of the 50 patients with pheochromocytoma, 7 (14% had coexisting vascular lesions including renal artery stenosis in 4, aortoarteritis in 1, aortic aneurysm in 1 and inferior vena cava thrombosis in 1. Pheochromocytoma was adrenal in 42 and extra adrenal in 8. Laparoscopic adrenalectomy was done in the patients. One patient with renal artery stenosis due to intimal fibrosis was subjected to percutaneous balloon angioplasty; the other three improved after adrenalectomy and lysis of fibrous adhesive bands. The patient with aortoarteritos was treated with oral steroids. Inferior vena cava thrombosis was reversed with anticoagulants. The patient with abdominal aortic aneurysm was advised for annual follow-up on account of its size of 4.5 cm and asymptomatic presentation. Conclusion: There are multiple mechanisms that can lead to renal artery stenosis and other vascular abnormalities in a case of pheochromocytoma. A high index of suspicion is necessary to enable both entities to be diagnosed preoperatively and allow proper planning of surgical therapy. Incomplete diagnosis may lead to persistent hypertension postoperatively in a case of associated renal artery stenosis.

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

EXTRA-OSSEOUS EWING SARCOMA

NARCIS (Netherlands)

van den Berg, Hendrik; Heinen, Richard C.; van der Pal, Heleen J.; Merks, Johannes H. M.

2009-01-01

Background: Clinical data and data on outcome of extra-osseous Ewing tumors are scarce. Procedure: After a search for Ewing tumors in the database of a single institution over a period of 20 years, 16 out of 192 cases were found to have extra-osseous primary tumors. Results: Ages at initial

Visualization of the extra-articular portion of the long head of the biceps tendon during intra-articular shoulder arthroscopy.

Science.gov (United States)

Festa, Anthony; Allert, Jesse; Issa, Kimona; Tasto, James P; Myer, Jonathan J

2014-11-01

To quantify the amount of the extra-articular long head of the biceps tendon (LHBT) seen during intra-articular shoulder arthroscopy by pulling the tendon into the joint with a probe through an anterior portal while viewing through a standard posterior portal. Intra-articular shoulder arthroscopy was performed on 10 forequarter cadaveric specimens. The extra-articular portion of the LHBT was evaluated by pulling the tendon into the joint with an arthroscopic probe inserted through an anterior portal. The tendon was marked at the pulley insertion on the humerus with a vascular clip before and after the tendon was pulled into the joint. An open deltopectoral approach was performed, and the amount of extra-articular tendon visualized was calculated as an absolute amount and in relation to nearby anatomic structures. An additional 1.9 cm (range, 1.4 to 2.6 cm) of extra-articular LHBT was viewed by pulling the tendon into the joint with an arthroscopic probe through an anterior portal during shoulder arthroscopy. This represented 30.8% of the extra-articular portion of the tendon, 47.7% of tendon in the bicipital groove, and 76.3% of the tendon that lies under the area from the pulley insertion to the distal edge of the transverse humeral ligament. During intra-articular shoulder arthroscopy, the extra-articular portion of the LHBT is incompletely visualized by pulling the tendon into the joint with a probe placed through an anterior portal while viewing through a standard posterior portal. An additional extra-articular portion of the LHBT may be viewed by pulling the tendon into the joint with an arthroscopic probe during shoulder arthroscopy. Copyright © 2014 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Optical spectroscopy of radiotherapy and photodynamic therapy responses in normal rat skin shows vascular breakdown products

Science.gov (United States)

Teles de Andrade, Cintia; Nogueira, Marcelo S.; Kanick, Stephen C.; Marra, Kayla; Gunn, Jason; Andreozzi, Jacqueline; Samkoe, Kimberley S.; Kurachi, Cristina; Pogue, Brian W.

2016-03-01

Photodynamic therapy (PDT) and radiotherapy are non-systemic cancer treatment options with different mechanisms of damage. So combining these techniques has been shown to have some synergy, and can mitigate their limitations such as low PDT light penetration or radiotherapy side effects. The present study monitored the induced tissue changes after PDT, radiotherapy, and a combination protocol in normal rat skin, using an optical spectroscopy system to track the observed biophysical changes. The Wistar rats were treated with one of the protocols: PDT followed by radiotherapy, PDT, radiotherapy and radiotherapy followed by PDT. Reflectance spectra were collected in order to observe the effects of these combined therapies, especially targeting vascular response. From the reflectance, information about oxygen saturation, met-hemoglobin and bilirubin concentration, blood volume fraction (BVF) and vessel radius were extracted from model fitting of the spectra. The rats were monitored for 24 hours after treatment. Results showed that there was no significant variation in the vessel size or BVF after the treatments. However, the PDT caused a significant increase in the met-hemoglobin and bilirubin concentrations, indicating an important blood breakdown. These results may provide an important clue on how the damage establishment takes place, helping to understand the effect of the combination of those techniques in order to verify the existence of a known synergistic effect.

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

Directory of Open Access Journals (Sweden)

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...

Adding an extra storey

DEFF Research Database (Denmark)

Engelmark, Jesper; Dahl, Torben; Melgaard, Ebbe

2007-01-01

of them had to be renovated after a shorter period. In stead of just replacing the original roof with a new one, it is now a days rather common to ad an extra storey where that is possible according to local planning. The reason is as a rule based on economical benefits, but very often this extra storey...

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

Particle Phenomenology of Compact Extra Dimensions

International Nuclear Information System (INIS)

Melbeus, Henrik

2012-01-01

This thesis is an investigation of the subject of extra dimensions in particle physics. In recent years, there has been a large interest in this subject. In particular, a number of models have been suggested that provide solutions to some of the problem with the current Standard Model of particle physics. These models typically give rise to experimental signatures around the TeV energy scale, which means that they could be tested in the next generation of high-energy experiments, such as the LHC. Among the most important of these models are the universal extra dimensions model, the large extra dimensions model by Arkani-Hamed, Dimopolous, and Dvali, and models where right-handed neutrinos propagate in the extra dimensions. In the thesis, we study phenomenological aspects of these models, or simple modifications of them. In particular, we focus on Kaluza-Klein dark matter in universal extra dimensions models, different aspects of neutrino physics in higher dimensions, and collider phenomenology of extra dimensions. In addition, we consider consequences of the enhanced renormalization group running of physical parameters in higher-dimensional models

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

Tendinopathy of the long head of the biceps tendon: histopathologic analysis of the extra-articular biceps tendon and tenosynovium

Directory of Open Access Journals (Sweden)

Streit JJ

2015-03-01

Full Text Available Jonathan J Streit,1 Yousef Shishani,1 Mark Rodgers,2 Reuben Gobezie1 1The Cleveland Shoulder Institute, 2Department of Pathology, University Hospitals of Cleveland, Cleveland, OH, USA Background: Bicipital tendinitis is a common cause of anterior shoulder pain, but there is no evidence that acute inflammation of the extra-articular long head of the biceps (LHB tendon is the root cause of this condition. We evaluated the histologic findings of the extra-articular portion of the LHB tendon and synovial sheath in order to compare those findings to known histologic changes seen in other tendinopathies. Methods: Twenty-six consecutive patients (mean age 45.4±13.7 years underwent an open subpectoral biceps tenodesis for anterior shoulder pain localized to the bicipital groove. Excised tendons were sent for histologic analysis. Specimens were graded using a semiquantitative scoring system to evaluate tenocyte morphology, the presence of ground substance, collagen bundle characteristics, and vascular changes. Results: Chronic inflammation was noted in only two of 26 specimens, and no specimen demonstrated acute inflammation. Tenocyte enlargement and proliferation, characterized by increased roundness and size of the cell and nucleus with proteoglycan matrix expansion and myxoid degenerative changes, was found in all 26 specimens. Abundant ground substance, collagen bundle changes, and increased vascularization were visualized in all samples. Conclusion: Anterior shoulder pain attributed to the biceps tendon does not appear to be due to an inflammatory process in most cases. The histologic findings of the extra-articular portion of the LHB tendon and synovial sheath are similar to the pathologic findings in de Quervain tenosynovitis at the wrist, and may be due to a chronic degenerative process similar to this and other tendinopathies of the body. Keywords: biceps tendinitis, biceps tendinopathy, tenosynovium, anterior shoulder pain, long head biceps

Inflation from periodic extra dimensions

Energy Technology Data Exchange (ETDEWEB)

Higaki, Tetsutaro [Department of Physics, Keio University, Kanagawa 223-8522 (Japan); Tatsuta, Yoshiyuki, E-mail: thigaki@rk.phys.keio.ac.jp, E-mail: y_tatsuta@akane.waseda.jp [Department of Physics, Waseda University, Tokyo 169-8555 (Japan)

2017-07-01

We discuss a realization of a small field inflation based on string inspired supergravities. In theories accompanying extra dimensions, compactification of them with small radii is required for realistic situations. Since the extra dimension can have a periodicity, there will appear (quasi-)periodic functions under transformations of moduli of the extra dimensions in low energy scales. Such a periodic property can lead to a UV completion of so-called multi-natural inflation model where inflaton potential consists of a sum of multiple sinusoidal functions with a decay constant smaller than the Planck scale. As an illustration, we construct a SUSY breaking model, and then show that such an inflaton potential can be generated by a sum of world sheet instantons in intersecting brane models on extra dimensions containing orbifold. We show also predictions of cosmic observables by numerical analyzes.

Extra-nodal extension is a significant prognostic factor in lymph node positive breast cancer.

Directory of Open Access Journals (Sweden)

Sura Aziz

Full Text Available Presence of lymph node (LN metastasis is a strong prognostic factor in breast cancer, whereas the importance of extra-nodal extension and other nodal tumor features have not yet been fully recognized. Here, we examined microscopic features of lymph node metastases and their prognostic value in a population-based cohort of node positive breast cancer (n = 218, as part of the prospective Norwegian Breast Cancer Screening Program NBCSP (1996-2009. Sections were reviewed for the largest metastatic tumor diameter (TD-MET, nodal afferent and efferent vascular invasion (AVI and EVI, extra-nodal extension (ENE, number of ENE foci, as well as circumferential (CD-ENE and perpendicular (PD-ENE diameter of extra-nodal growth. Number of positive lymph nodes, EVI, and PD-ENE were significantly increased with larger primary tumor (PT diameter. Univariate survival analysis showed that several features of nodal metastases were associated with disease-free (DFS or breast cancer specific survival (BCSS. Multivariate analysis demonstrated an independent prognostic value of PD-ENE (with 3 mm as cut-off value in predicting DFS and BCSS, along with number of positive nodes and histologic grade of the primary tumor (for DFS: P = 0.01, P = 0.02, P = 0.01, respectively; for BCSS: P = 0.02, P = 0.008, P = 0.02, respectively. To conclude, the extent of ENE by its perpendicular diameter was independently prognostic and should be considered in line with nodal tumor burden in treatment decisions of node positive breast cancer.

Splenic Artery Syndrome After Orthotopic Liver Transplantation: Treatment With the Amplatzer Vascular Plug

International Nuclear Information System (INIS)

Maurer, M. H.; Mogl, M. T.; Podrabsky, P.; Denecke, T.; Grieser, C.; Fröling, V.; Scheurig-Münkler, C.; Guckelberger, O.; Kroencke, T. J.

2011-01-01

Purpose: To evaluate the safety and efficacy of the Amplatzer vascular plug (AVP) for embolization of the splenic artery in patients with hepatic hypoperfusion after orthotopic liver transplantation (OLT). Materials and Methods: Thirteen patients (9 men and 4 women) with a mean age of 56 years (range 22–70) who developed splenic artery syndrome after OLT with decreased liver perfusion and clinically relevant impairment of liver function (increased transaminase or serum bilirubin levels, thrombocytopenia, and/or therapy-refractory ascites) were treated by embolization of the proximal third of the splenic artery using the AVP. The plugs ranged in diameter from 6 to 16 mm, and they were introduced through femoral (n = 9), axillary (n = 3), or brachial (n = 1) access using a 5F or 8F guiding catheter. Results: The plugs were successfully placed, and complete occlusion of the splenic artery was achieved in all patients. Placement of two plugs was necessary for complete occlusion in 3 of the 13 patients. Occlusion took on average 10 min (range 4–35). There was no nontarget embolization or plug migration into more distal segments of the splenic artery. All patients showed improved arterial perfusion, including the liver periphery, on postinterventional angiogram. After embolization, liver function parameters (transaminase and bilirubin levels) improved with normalization of concomitant thrombocytopenia and a decrease in ascites volume. Conclusion: Our initial experience in a small patient population with SAS suggests that the AVP enables precise embolization of the proximal splenic artery, thus providing safe and effective treatment for poor liver perfusion after OLT due to SAS.

Supersymmetry breaking with extra dimensions

International Nuclear Information System (INIS)

Zwirner, Fabio

2004-01-01

This talk reviews some aspects of supersymmetry breaking in the presence of extra dimensions. The first part is a general introduction, recalling the motivations for supersymmetry and extra dimensions, as well as some unsolved problems of four-dimensional models of supersymmetry breaking. The central part is a more focused introduction to a mechanism for (super)symmetry breaking, proposed first by Scherk and Schwarz, where extra dimensions play a crucial role. The last part is devoted to the description of some recent results and of some open problems. (author)

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

Hydraulic efficiency and safety of vascular and non-vascular components in Pinus pinaster leaves.

Science.gov (United States)

Charra-Vaskou, Katline; Badel, Eric; Burlett, Régis; Cochard, Hervé; Delzon, Sylvain; Mayr, Stefan

2012-09-01

Leaves, the distal section of the soil-plant-atmosphere continuum, exhibit the lowest water potentials in a plant. In contrast to angiosperm leaves, knowledge of the hydraulic architecture of conifer needles is scant. We investigated the hydraulic efficiency and safety of Pinus pinaster needles, comparing different techniques. The xylem hydraulic conductivity (k(s)) and embolism vulnerability (P(50)) of both needle and stem were measured using the cavitron technique. The conductance and vulnerability of whole needles were measured via rehydration kinetics, and Cryo-SEM and 3D X-ray microtomographic observations were used as reference tools to validate physical measurements. The needle xylem of P. pinaster had lower hydraulic efficiency (k(s) = 2.0 × 10(-4) m(2) MPa(-1) s(-1)) and safety (P(50) = - 1.5 MPa) than stem xylem (k(s) = 7.7 × 10(-4) m(2) MPa(-1) s(-1); P(50) = - 3.6 to - 3.2 MPa). P(50) of whole needles (both extra-vascular and vascular pathways) was - 0.5 MPa, suggesting that non-vascular tissues were more vulnerable than the xylem. During dehydration to - 3.5 MPa, collapse and embolism in xylem tracheids, and gap formation in surrounding tissues were observed. However, a discrepancy in hydraulic and acoustic results appeared compared with visualizations, arguing for greater caution with these techniques when applied to needles. Our results indicate that the most distal parts of the water transport pathway are limiting for hydraulics of P. pinaster. Needle tissues exhibit a low hydraulic efficiency and low hydraulic safety, but may also act to buffer short-term water deficits, thus preventing xylem embolism.

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

Quantifying inbreeding avoidance through extra-pair reproduction.

Science.gov (United States)

Reid, Jane M; Arcese, Peter; Keller, Lukas F; Germain, Ryan R; Duthie, A Bradley; Losdat, Sylvain; Wolak, Matthew E; Nietlisbach, Pirmin

2015-01-01

Extra-pair reproduction is widely hypothesized to allow females to avoid inbreeding with related socially paired males. Consequently, numerous field studies have tested the key predictions that extra-pair offspring are less inbred than females' alternative within-pair offspring, and that the probability of extra-pair reproduction increases with a female's relatedness to her socially paired male. However, such studies rarely measure inbreeding or relatedness sufficiently precisely to detect subtle effects, or consider biases stemming from failure to observe inbred offspring that die during early development. Analyses of multigenerational song sparrow (Melospiza melodia) pedigree data showed that most females had opportunity to increase or decrease the coefficient of inbreeding of their offspring through extra-pair reproduction with neighboring males. In practice, observed extra-pair offspring had lower inbreeding coefficients than females' within-pair offspring on average, while the probability of extra-pair reproduction increased substantially with the coefficient of kinship between a female and her socially paired male. However, simulations showed that such effects could simply reflect bias stemming from inbreeding depression in early offspring survival. The null hypothesis that extra-pair reproduction is random with respect to kinship therefore cannot be definitively rejected in song sparrows, and existing general evidence that females avoid inbreeding through extra-pair reproduction requires reevaluation given such biases. © 2014 The Author(s). Evolution © 2014 The Society for the Study of Evolution.

Índices para estimar o tempo transcorrido entre o surto hemorrágico subaracnóideo e a colheita de líquido cefalorraqueano Appraisement of the time elapsed between cerebro-vascular accidents and cerebrospinal fluid examination. An experimental study

Directory of Open Access Journals (Sweden)

José M. Marlet

1973-12-01

Full Text Available O autor simulou, experimentalmente, acidente vascular cerebral hemorrágico em cães injetando sangue do próprio animal no espaço subaracnóideo, colhendo amostras diárias de LCR durante 14 dias, sendo estudada a evolução das concentrações de oxiemoglobina e de bilirrubina, empregando métodos espectrofotométricos. Define um coeficiente hemoglobínico como a relação entre a concentração de oxiemoglobina e o total de pigmentos do LCR e um índice hemoglobina-bilirrubina como a relação entre as concentrações de oxiemoglobina e bilirrubina. Depois do tratamento estatístico, chega à conclusão de que ambos permitem estimar o tempo transcorrido desde o surto hemorrágico subaracnóideo e a colheita de LCR. São apresentadas sugestões quanto à aplicabilidade prática destes indicadores em Neurologia e Medicina Preventiva.Hemorrhagic cerebro-vascular accidents were simulated in dogs by injecting their own blood in the subarachnoidal space. Gathering daily samples of cerebrospinal fluid during 14 days the evolution of the concentrations of oxyhemoglobin and bilirubin using the spectrosphotometric method was studied. The author defines hemoglobin coefficient as being the relatinship between the oxyhemoglobin concentration and the sum of the cerebrospinal fluid pigments and the hemoglobin-bilirubin index as the relationship between the oxyhemoglobin and the bilirubin concentration. After statistical treatment the author concludes that both permit to calculate the time span between the subarachnoidal hemorrhage and the examination of the cerebrospinal fluid. Some suggestions on the practical applicability of these indexes in Clinical Neurology and Preventive Medicine are discussed.

Extra-anatomic bypass for recurrent abdominal aortic and renal in-stent stenoses following radiotherapy for neuroblastoma.

Science.gov (United States)

Luehr, Maximilian; Siepe, Matthias; Beyersdorf, Friedhelm; Schlensak, Christian

2009-04-01

We describe the case of an 11-year-old girl with an abdominal neuroblastoma which was operated and intraoperatively irradiated nine years ago. After six years, she developed stenoses of the infrarenal abdominal aorta and both renal arteries. Initial treatment of the stenosed vessels comprised endovascular balloon dilatations and repeated stent-graft implantations, including drug eluting stents. However, severe in-stent stenoses occurred during follow-up and the girl developed acute renal failure. Open surgery was performed with two extra-anatomic bypasses, a thoracic-to-abdominal aortic bypass and a left iliac-to-renal bypass, on an urgent basis. The postoperative course was uneventful and the patient was discharged home two weeks after the operation with full recovery of renal function. We conclude that endovascular stent-graft placement in children can only be a palliative treatment due to outgrowing of the stent-graft and the potential risk of re-stenosis, especially after a history of irradiation. Vascular surgery with placement of extra-anatomic bypasses will provide a definite treatment.

Collapse of large extra dimensions

International Nuclear Information System (INIS)

Geddes, James

2002-01-01

In models of spacetime that are the product of a four-dimensional spacetime with an 'extra' dimension, there is the possibility that the extra dimension will collapse to zero size, forming a singularity. We ask whether this collapse is likely to destroy the spacetime. We argue, by an appeal to the four-dimensional cosmic censorship conjecture, that--at least in the case when the extra dimension is homogeneous--such a collapse will lead to a singularity hidden within a black string. We also construct explicit initial data for a spacetime in which such a collapse is guaranteed to occur and show how the formation of a naked singularity is likely avoided

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.

Introduction to Extra Dimensions

Energy Technology Data Exchange (ETDEWEB)

Rizzo, Thomas G.; /SLAC

2010-04-29

Extra dimensions provide a very useful tool in addressing a number of the fundamental problems faced by the Standard Model. The following provides a very basic introduction to this very broad subject area as given at the VIII School of the Gravitational and Mathematical Physics Division of the Mexican Physical Society in December 2009. Some prospects for extra dimensional searches at the 7 TeV LHC with {approx}1 fb{sup -1} of integrated luminosity are provided.

Cosmology in theories with extra dimensions

International Nuclear Information System (INIS)

Kolb, E.W.

1985-01-01

Some possible cosmological effects of the existence of extra compact dimensions are discussed. Particular attention is given to the possibility that extra dimensions might naturally lead to an inflationary Universe scenario

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.

Color coded duplex sonography. Interdisciplinary vascular ultrasonography; Farbkodierte Duplexsonographie. Interdisziplinaerer vaskulaerer Ultraschall

Energy Technology Data Exchange (ETDEWEB)

Kubale, R. [Institut fuer Radiologie, Sonographie und Nuklearmedizin, Pirmasens (Germany); Stiegler, H. [Staedtisches Krankenhaus Schwabing, Muenchen (Germany). 7. Medizinische Abt.

2002-07-01

An interdisciplinary team of experts impart the state of the art in color coded duplex sonography applied for examination of all anatomic areas. Detailed information is given for every vascular area, describing the examination procedure, possible origins of mistakes or faults, and means to avoid them. In addition to the classical applications, eg. for examination of the extra- and intracranial vessels, vessels of the limbs, visceral vessels and the vessels of liver and kidney, there are chapters devoted to: haemodialysis shunts, arteriovenous malformations, duplex sonography of the penis, tumor vascularisation. (orig./CB) [German] Ein interdisziplinaeres Autorenteam vermittelt Ihnen den State of the Art der FKDS fuer alle anatomischen Regionen. Fuer jede der Gefaessregionen werden detaillierte Angaben zum Untersuchungsablauf, zu moeglichen Fehlerquellen und zu deren Vermeidung geboten. Neben den klassischen Anwendungen bei der Untersuchung - der extra- und intrakraniellen Gefaesse, - der Extremitaetengefaesse, - der viszeralen Gefaesse sowie der Gefaesse von Niere und Leber finden Sie Kapitel zu den Themen: Haemodialyseshunt, arteriovenoese Malformationen, Duplexsonographie des Penis und Tumorvaskularisation. (orig./AJ)

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

Screening and validation of EXTraS data products

Science.gov (United States)

Carpano, Stefania; Haberl, F.; De Luca, A.; Tiengo, A.: Israel, G.; Rodriguez, G.; Belfiore, A.; Rosen, S.; Read, A.; Wilms, J.; Kreikenbohm, A.; Law-Green, D.

2015-09-01

The EXTraS project (Exploring the X-ray Transient and variable Sky) is aimed at fullyexploring the serendipitous content of the XMM-Newton EPIC database in the timedomain. The project is funded within the EU/FP7-Cooperation Space framework and is carried out by a collaboration including INAF (Italy), IUSS (Italy), CNR/IMATI (Italy), University of Leicester (UK), MPE (Germany) and ECAP (Germany). The several tasks consist in characterise aperiodicvariability for all 3XMM sources, search for short-term periodic variability on hundreds of thousands sources, detect new transient sources that are missed by standard source detection and hence not belonging to the 3XMM catalogue, search for long term variability by measuring fluxes or upper limits for both pointed and slew observations, and finally perform multiwavelength characterisation andclassification. Screening and validation of the different products is essentially in order to reject flawed results, generated by the automatic pipelines. We present here the screening tool we developed in the form of a Graphical User Interface and our plans for a systematic screening of the different catalogues.

Role of hydrogen sulfide in portal hypertension and esophagogastric junction vascular disease

Science.gov (United States)

Wang, Chao; Han, Juan; Xiao, Liang; Jin, Chang-E; Li, Dong-Jian; Yang, Zhen

2014-01-01

AIM: To investigate the association between endogenous hydrogen sulfide (H2S) and portal hypertension as well as its effect on vascular smooth muscle cells. METHODS: Portal hypertension patients were categorized by Child-Pugh score based on bilirubin and albumin levels, prothrombin time, ascites and hepatic encephalopathy. Plasma H2S concentrations and portal vein diameters (PVDs) were compared between portal hypertension patients and control participants, as well as between portal hypertension patients with varying degrees of severity. In addition, we established a rabbit hepatic schistosomiasis portal hypertension (SPH) model and analyzed liver morphology, fibrosis grade, plasma and liver tissue H2S concentrations, as well as cystathionine γ-lyase (CSE) activity and phosphorylated extracellular signal-regulated kinase (pERK)1/2, B cell lymphoma (Bcl)-2 and Bcl-XL expression in portal vein smooth muscle cells, in addition to their H2S-induced apoptosis rates. RESULTS: In portal hypertension patients, endogenous H2S levels were significantly lower than those in healthy controls. The more severe the disease was, the lower were the H2S plasma levels, which were inversely correlated with PVD and Child-Pugh score. Liver tissue H2S concentrations and CSE expression were significantly lower in the SPH rabbit livers compared with the control animals, starting at 3 wk, whereas pERK 1/2 expressions gradually increased 12-20 wk after SPH model establishment. In portal vein smooth muscle cells, increasing H2S levels led to increased apoptosis, while Bcl-2 and Bcl-XL expression decreased. CONCLUSION: H2S prevents vascular restructuring caused by excessive proliferation of smooth muscle cells via apoptosis induction, which helps to maintain normal vascular structures. PMID:24574782

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...

Towards the Proper Integration of Extra-Functional Requirements

Directory of Open Access Journals (Sweden)

Elke Hochmuller

1999-05-01

Full Text Available In spite of the many achievements in software engineering, proper treatment of extra-functional requirements (also known as non-functional requirements within the software development process is still a challenge to our discipline. The application of functionality-biased software development methodologies can lead to major contradictions in the joint modelling of functional and extra-functional requirements. Based on a thorough discussion on the nature of extra-functional requirements as well as on open issues in coping with them, this paper emphasizes the role of extra-functional requirements in the software development process. Particularly, a framework supporting the explicit integration of extra functional requirements into a conventional phase-driven process model is proposed and outlined.

Extra dimensions and color confinement

Energy Technology Data Exchange (ETDEWEB)

Pleitez, V

1995-04-01

An extension of the ordinary four dimensional Minkowski space by introducing additional dimensions which have their own Lorentz transformation is considered. Particles can transform in a different way under each Lorentz group. It is shown that only quark interactions are slightly modified and that color confinement automatic since these degrees of freedom run only in the extra dimensions. No compactification of the extra dimensions is needed. (author). 4 refs.

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

Bio-absorbable antibiotic impregnated beads for the treatment of prosthetic vascular graft infections.

Science.gov (United States)

Genovese, Elizabeth A; Avgerinos, Efthymios D; Baril, Donald T; Makaroun, Michel S; Chaer, Rabih A

2016-12-01

There is limited investigation into the use of bio-absorbable antibiotic beads for the treatment of prosthetic vascular graft infections. Our goal was to investigate the rates of infection eradication, graft preservation, and limb salvage in patients who are not candidates for graft explant or extensive reconstruction. A retrospective review of patients implanted with antibiotic impregnated bio-absorbable calcium sulfate beads at a major university center was conducted. Six patients with prosthetic graft infections were treated with bio-absorbable antibiotics beads from 2012-2014. Grafts included an aortobifemoral, an aorto-hepatic/superior mesenteric artery, and four extra-anatomic bypasses. Pathogens included Gram-positive and Gram-negative bacteria. Half of the patients underwent graft explant with reconstruction and half debridement of the original graft, all with antibiotic bead placement around the graft. Mean follow-up was 7.3 ± 8.3 months; all patients had infection resolution, healed wounds, and 100% graft patency, limb salvage, and survival. This report details the successful use of bio-absorbable antibiotic beads for the treatment prosthetic vascular graft infections in patients at high risk for graft explant or major vascular reconstruction. At early follow-up, we demonstrate successful infection suppression, graft preservation, and limb salvage with the use of these beads in a subset of vascular patients. © The Author(s) 2016.

Bio-absorbable antibiotic impregnated beads for the treatment of prosthetic vascular graft infections

Science.gov (United States)

Genovese, Elizabeth A; Avgerinos, Efthymios D; Baril, Donald T; Makaroun, Michel S; Chaer, Rabih A

2017-01-01

Objective There is limited investigation into the use of bio-absorbable antibiotic beads for the treatment of prosthetic vascular graft infections. Our goal was to investigate the rates of infection eradication, graft preservation, and limb salvage in patients who are not candidates for graft explant or extensive reconstruction. Methods A retrospective review of patients implanted with antibiotic impregnated bio-absorbable calcium sulfate beads at a major university center was conducted. Results Six patients with prosthetic graft infections were treated with bio-absorbable antibiotics beads from 2012–2014. Grafts included an aortobifemoral, an aorto-hepatic/superior mesenteric artery, and four extra-anatomic bypasses. Pathogens included Gram-positive and Gram-negative bacteria. Half of the patients underwent graft explant with reconstruction and half debridement of the original graft, all with antibiotic bead placement around the graft. Mean follow-up was 7.3±8.3 months; all patients had infection resolution, healed wounds, and 100% graft patency, limb salvage, and survival. Conclusion This report details the successful use of bio-absorbable antibiotic beads for the treatment prosthetic vascular graft infections in patients at high risk for graft explant or major vascular reconstruction. At early follow-up, we demonstrate successful infection suppression, graft preservation, and limb salvage with the use of these beads in a subset of vascular patients. PMID:26896286

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.

23 CFR 635.120 - Changes and extra work.

Science.gov (United States)

2010-04-01

... CONSTRUCTION AND MAINTENANCE Contract Procedures § 635.120 Changes and extra work. (a) Following authorization to proceed with a project, all major changes in the plans and contract provisions and all major extra... to what constitutes a non-major change and non-major extra work. (c) Changes in contract time, as...

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

Science.gov (United States)

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.

Directory of Open Access Journals (Sweden)

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.

Osteocalcin, Vascular Calcification, and Atherosclerosis: A Systematic Review and Meta-analysis

Directory of Open Access Journals (Sweden)

Sophie A. Millar

2017-07-01

Full Text Available BackgroundOsteocalcin (OC is an intriguing hormone, concomitantly being the most abundant non-collagenous peptide found in the mineralized matrix of bone, and expanding the endocrine function of the skeleton with far-reaching extra-osseous effects. A new line of enquiry between OC and vascular calcification has emerged in response to observations that the mechanism of vascular calcification resembles that of bone mineralisation. To date, studies have reported mixed results. This systematic review and meta-analysis aimed to identify any association between OC and vascular calcification and atherosclerosis.Methods and resultsDatabases were searched for original, peer reviewed human studies. A total of 1,453 articles were retrieved, of which 46 met the eligibility criteria. Overall 26 positive, 17 negative, and 29 neutral relationships were reported for assessments between OC (either concentration in blood, presence of OC-positive cells, or histological staining for OC and extent of calcification or atherosclerosis. Studies that measured OC-positive cells or histological staining for OC reported positive relationships (11 studies. A higher percentage of Asian studies found a negative relationship (36% in contrast to European studies (6%. Studies examining carboxylated and undercarboxylated forms of OC in the blood failed to report consistent results. The meta-analysis found no significant difference between OC concentration in the blood between patients with “atherosclerosis” and control (p = 0.13, n = 1,197.ConclusionNo definitive association was determined between OC and vascular calcification or atherosclerosis; however, the presence of OC-positive cells and histological staining had a consistent positive correlation with calcification or atherosclerosis. The review highlighted several themes, which may influence OC within differing populations leading to inconclusive results. Large, longitudinal studies are required to further

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

Directory of Open Access Journals (Sweden)

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 search for extra dimensions

International Nuclear Information System (INIS)

Abel, Steven; March-Russell, John

2000-01-01

The possibility of extra dimensions, beyond the three dimensions of space of our everyday experience, sometimes crops up as a convenient, if rather vague, plot in science fiction. In science, however, the idea of extra dimensions has a rich history, dating back at least as far as the 1920s. Recently there has been a remarkable renaissance in this area due to the work of a number of theoretical physicists. It now seems possible that we, the Earth and, indeed, the entire visible universe are stuck on a membrane in a higher-dimensional space, like dust particles that are trapped on a soap bubble. In this article the authors look at the major issues behind this new development. Why, for example, don't we see these extra dimensions? If they exist, how can we detect them? And perhaps the trickiest question of all: how did this fanciful idea come to be considered in the first place? (U.K.)

Extra force and extra mass from non-compact Kaluza-Klein theory in a cosmological model

International Nuclear Information System (INIS)

MadrizAguilar, J.E.; Bellini, M.

2005-01-01

Using the Hamilton-Jacobi formalism, we study extra force and extra mass in a recently introduced non-compact Kaluza-Klein cosmological model. We examine the inertial 4D mass m 0 of the inflaton field on a 4D FRW bulk in two examples. We find that m 0 has a geometrical origin and antigravitational effects on a non-inertial 4D bulk should be a consequence of the motion of the fifth coordinate with respect to the 4D bulk. (orig.)

Extra osseous primary Ewing's sarcoma.

Science.gov (United States)

Ali, Syed Asad; Muhammad, Agha Taj; Soomro, Abdul Ghani; Siddiqui, Akmal Jamal

2010-01-01

The case of 20 years old boy with an extra osseous Ewing's sarcoma is described. He was initially diagnosed as a case of infiltrative malignant tumour of left suprarenal gland on the basis of preoperative workup but postoperative biopsy of surgically excised specimen confirmed Extra-osseous Ewing's Sarcoma (EES) suprarenal gland with no evidence of malignancy on skeletal scintiscan, bone marrow aspirate and histopathology Suprarenal location of primary EES is unknown and probably has not been reported in literature. We report a unique case of EES.

Towards the Proper Integration of Extra-Functional Requirements

OpenAIRE

Elke Hochmuller

1999-01-01

In spite of the many achievements in software engineering, proper treatment of extra-functional requirements (also known as non-functional requirements) within the software development process is still a challenge to our discipline. The application of functionality-biased software development methodologies can lead to major contradictions in the joint modelling of functional and extra-functional requirements. Based on a thorough discussion on the nature of extra-functional requirements as wel...

[Bone metabolism and cardiovascular function update. Estrogen and its therapeutic potential for bone and vascular health].

Science.gov (United States)

Ohta, Hiroaki

2014-07-01

Despite its long-standing role as a "guardian angel" for the female body, estrogen has recently been dethroned from its status as an "elixir" and its use has been restricted due to its oncogenic potential as well as its coagulation system-associated risk. However, it is recognized that estrogen not only works against bone resorption but also improves vascular function. In this regard, it is suggested that estrogen may have a role in improving deteriorated bone quality through its antioxidant action, while this same effect with the SERMs, which may be accounted for by the presence of estrogen, remains yet to be established. Not only evidence needs to be accumulated to support the vascular effects of the SERMs, but their pleiotropic, rather than extra-skeletal, effects, as likely mediated by the estrogen receptors distributed throughout the body, remain to be elucidated.

Extra-pulmonary tuberculosis in Uyo, South - South, Nigeria | Abudu ...

African Journals Online (AJOL)

Background: Tuberculosis is a disease of the poor, affecting the pulmonary and extra-pulmonary organs. Objectives: To assess the frequency and morphologic pattern of extra-pulmonary tuberculosis as well as determining the occurrence of other acid fast organisms from extra-pulmonary tissue biopsies using common ...

Major Vascular Neurocognitive Disorder: A Reappraisal to Vascular Dementia

Directory of Open Access Journals (Sweden)

Emre Kumral

2017-03-01

Full Text Available Major vascular neurocognitive disorder (NCD is the second leading form of dementia after Alzheimer’s disease, accounting for 17-20% of all dementias. Vascular NCD is a progressive disease caused by reduced cerebral blood flow related to multiple large volume or lacunar infarcts that induce a sudden onset and stepwise decline in cognitive abilities. Despite its prevalence and clinical importance, there is still controversy in the terminology of vascular NCD. Only after the release of Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5 (2013 did the American Psychiatric Association define vascular dementia as “major vascular NCD”. This review includes an overview of risk factors, pathophysiology, types, diagnostic and clinical features of major vascular NCD, and current treatment options of vascular NCD regarding to DSM-5 criteria

Extra colonic Findings on CT Colonography in Symptomatic Patients

International Nuclear Information System (INIS)

Drahovska, I.; Nigut, F.; Mach, P.; Lazurova, I.; Gombosova, L.

2011-01-01

The paper is an analysis of the consequences of the extra colonic findings identified on CT colonography examination of symptomatic patients and the validity of the intravenous application of contrast medium in this examination. The authors enrolled 252 patients, who underwent CT colonogprahy.128 extra colonic findings was identified in 80 patients (31.74%). The average age was 65.62 years (SD = 12.7, min. age was 29, max. age. 85 years). According the clinical significance the extra colonic findings have been divided into three groups – low, moderate and very important extra colonic findings. Low significant findings were 68 (53.12%), moderate 26 (20.31%) and very important extra colonic findings were 34 (26.56%), of which 30 were malignant nature. (author)

Vascular ring presenting as dysphagia in an adult woman: a case report.

Science.gov (United States)

Powell, B L

2017-01-01

A 48-year-old woman was seen in a surgical outpatient clinic with a 2 year history of progressive dysphagia with occasional regurgitation, partially controlled with a proton pump inhibitor. Primary investigations of pH testing and gastroscopy were normal, although a barium swallow study revealed significant hold-up at the aortic arch impression and a posterior right-sided oesophageal impression suggestive of a right-sided aortic arch. A follow-up computed tomography angiogram discovered a vascular ring encircling the trachea and oesophagus, formed by a right-sided aortic arch with aberrant aortic branches, and a Kommerell's diverticulum. It was deemed that the patient's symptoms were related to this vascular ring. The patient underwent stage-one surgery - an extra-anatomic bypass of the double aortic arch and right subclavian artery - and 4 months later a stent graft insertion over the origin of the diverticulum with the aim of complete symptomatic relief. This case presents a common symptom familiar to any clinician (dysphagia), which has been caused by a rare pathology. It is even more unusual that this should present itself in adulthood.

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.

Additive Manufacturing of Vascular Grafts and Vascularized Tissue Constructs.

Science.gov (United States)

Elomaa, Laura; Yang, Yunzhi Peter

2017-10-01

There is a great need for engineered vascular grafts among patients with cardiovascular diseases who are in need of bypass therapy and lack autologous healthy blood vessels. In addition, because of the severe worldwide shortage of organ donors, there is an increasing need for engineered vascularized tissue constructs as an alternative to organ transplants. Additive manufacturing (AM) offers great advantages and flexibility of fabrication of cell-laden, multimaterial, and anatomically shaped vascular grafts and vascularized tissue constructs. Various inkjet-, extrusion-, and photocrosslinking-based AM techniques have been applied to the fabrication of both self-standing vascular grafts and porous, vascularized tissue constructs. This review discusses the state-of-the-art research on the use of AM for vascular applications and the key criteria for biomaterials in the AM of both acellular and cellular constructs. We envision that new smart printing materials that can adapt to their environment and encourage rapid endothelialization and remodeling will be the key factor in the future for the successful AM of personalized and dynamic vascular tissue applications.

search of extra space dimensions with ATLAs

Indian Academy of Sciences (India)

search of extra space dimensions with ATLAs. AMBREEsH GUPTA (for the ATLAs Collaboration). 5640 South Ellis Avenue, Enrico Fermi Institute, University of Chicago, Chicago,. IL 60637, USA. Abstract. If extra spatial dimensions were to exist, they could provide a solution to the hierarchy problem. The studies done by the ...

Extra-pair mating and evolution of cooperative neighbourhoods.

Directory of Open Access Journals (Sweden)

Sigrunn Eliassen

Full Text Available A striking but unexplained pattern in biology is the promiscuous mating behaviour in socially monogamous species. Although females commonly solicit extra-pair copulations, the adaptive reason has remained elusive. We use evolutionary modelling of breeding ecology to show that females benefit because extra-pair paternity incentivizes males to shift focus from a single brood towards the entire neighbourhood, as they are likely to have offspring there. Male-male cooperation towards public goods and dear enemy effects of reduced territorial aggression evolve from selfish interests, and lead to safer and more productive neighbourhoods. The mechanism provides adaptive explanations for the common empirical observations that females engage in extra-pair copulations, that neighbours dominate as extra-pair sires, and that extra-pair mating correlates with predation mortality and breeding density. The models predict cooperative behaviours at breeding sites where males cooperate more towards public goods than females. Where maternity certainty makes females care for offspring at home, paternity uncertainty and a potential for offspring in several broods make males invest in communal benefits and public goods. The models further predict that benefits of extra-pair mating affect whole nests or neighbourhoods, and that cuckolding males are often cuckolded themselves. Derived from ecological mechanisms, these new perspectives point towards the evolution of sociality in birds, with relevance also for mammals and primates including humans.

Vascular map combined with CT colonography for evaluating candidates for laparoscopic colorectal surgery

International Nuclear Information System (INIS)

Flor, Nicola; Ceretti, Andrea Pisani; Maroni, Nirvana; Opocher, Enrico; Cornalba, Gianpaolo; Campari, Alessandro; Ravelli, Anna; Lombardi, Maria Antonietta

2015-01-01

Contrast-enhanced computed tomography colonography (CE-CTC) is a useful guide for the laparoscopic surgeon to avoid incorrectly removing the colonic segment and the failure to diagnose of synchronous colonic and extra-colonic lesions. Lymph node dissection and vessel ligation under a laparoscopic approach can be time-consuming and can damage vessels and organs. Moreover, mesenteric vessels have extreme variations in terms of their courses and numbers. We describe the benefit of using an abdominal vascular map created by CE-CTC in laparoscopic colorectal surgery candidates. We describe patients with different diseases (colorectal cancer, diverticular disease, and inflammatory bowel disease) who underwent CE-CTC just prior to laparoscopic surgery

Vascular map combined with CT colonography for evaluating candidates for laparoscopic colorectal surgery

Energy Technology Data Exchange (ETDEWEB)

Flor, Nicola; Ceretti, Andrea Pisani; Maroni, Nirvana; Opocher, Enrico; Cornalba, Gianpaolo [Azienda Ospedaliera San Paolo, Milan (Italy); Campari, Alessandro; Ravelli, Anna; Lombardi, Maria Antonietta [University degli Studi di Milano, Milan (Italy)

2015-08-15

Contrast-enhanced computed tomography colonography (CE-CTC) is a useful guide for the laparoscopic surgeon to avoid incorrectly removing the colonic segment and the failure to diagnose of synchronous colonic and extra-colonic lesions. Lymph node dissection and vessel ligation under a laparoscopic approach can be time-consuming and can damage vessels and organs. Moreover, mesenteric vessels have extreme variations in terms of their courses and numbers. We describe the benefit of using an abdominal vascular map created by CE-CTC in laparoscopic colorectal surgery candidates. We describe patients with different diseases (colorectal cancer, diverticular disease, and inflammatory bowel disease) who underwent CE-CTC just prior to laparoscopic surgery.

Dimensiones Extra y los Límites de la Física Dimensiones Extra y los Límites de la Física

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Selim Gómez Ávila

2012-02-01

Full Text Available The history and cultural impact of extra dimensional models in physics is briefl y examined. Emphasis is put in the influence in the fine arts, and in particular the case of Marcel Duchamp is used as an example. Some perspectives of the study of extra dimensions aresketched.Se examina brevemente la historia y el impacto cultural de modelos de dimensiones extraen física. Se enfatiza la influencia en las bellas artes, y en particular el caso de Marcel Duchamp es usado como ejemplo. Se bosquejan algunas perspectivas del estudio de dimensiones extra.

Extra-pair parentage and personality in a cooperatively breeding bird

NARCIS (Netherlands)

Edwards, Hannah A; Dugdale, Hannah L; Richardson, David S; Komdeur, Jan; Burke, Terry

Abstract: Why so much variation in extra-pair parentage occurs within and among populations remains unclear. Often the fitness costs and benefits of extra-pair parentage are hypothesised to explain its occurrence; therefore, linking extra-pair parentage with traits such as personality (behavioural

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

Non-invasive vascular imaging: assessing tumour vascularity

International Nuclear Information System (INIS)

Delorme, S.; Knopp, M.V.

1998-01-01

Non-invasive assessment of vascularity is a new diagnostic approach to characterise tumours. Vascular assessment is based on the pathophysiology of tumour angiogenesis and its diagnostic implications for tumour biology, prognosis and therapy response. Two current techniques investigating vascular features in addition to morphology are Doppler ultrasonography and contrast-enhanced MRI. Diagnostic differentiation has been shown to be possible with Doppler, and a high degree of observed vascularity could be linked to an aggressive course of the disease. Dynamic MRI using gadolinium chelates is already used clinically to detect and differentiate tumours. The histological correlation shows that capillary permeability is increased in malignant tumours and is the best criterion for differentiation from benign processes. Permeability and perfusion factors seem to be more diagnostic than overall vessel density. New clinical applications are currently being established for therapy monitoring. Further instrumental developments will bring harmonic imaging in Doppler, and faster imaging techniques, higher spatial resolution and novel pharmacokinetic concepts in MRI. Upcoming contrast agents for both Doppler and MRI will further improve estimation of intratumoural blood volume and vascular permeability. (orig.)

CKM pattern from localized generations in extra dimension

International Nuclear Information System (INIS)

Matti, C.

2006-01-01

We revisit the issue of the quark masses and mixing angles in the framework of large extra dimension. We consider three identical standard model families resulting from higher-dimensional fields localized on different branes embedded in a large extra dimension. Furthermore we use a decaying profile in the bulk different form previous works. With the Higgs field also localized on a different brane, the hierarchy of masses between the families results from their different positions in the extra space. When the left-handed doublet and the right-handed singlets are localized with different couplings on the branes, we found a set of brane locations in one extra dimension which leads to the correct quark masses and mixing angles with the sufficient strength of CP-violation. We see that the decaying profile of the Higgs field plays a crucial role for producing the hierarchies in a rather natural way. (orig.)

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.

The comparative characteristic of extra- and intracranial hemodynamics in patients with traumatic brain injury in the long-term period

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Shkolnyk V.M.

2017-04-01

Full Text Available Traumatic brain injury (TBI remains an actual problem of modern medicine, as well as of economic and social sectors. Vascular factor plays a leading role in forming of the clinical presentation of the disease in the long-term period of TBI. The aim of the study was to clarify the characteristics of hemodynamic changes at different levels of cerebral blood supply (main extra- and intracranial arteries and level of cerebral vessels depending on the severity of TBI. We examined 100 patients in the long-term period of mild, moderate and severe TBI. All patients underwent rheoencephalography, ultrasound duplex scanning of the main arteries of the head and neck with transcranial dopplerography and functional test with visual load. Extracranial vascular changes in the long-term period of TBI are characterized by significant increase of carotid intima-media thickness and the diameters of right internal carotid artery and left internal carotid artery together with the severity of TBI. The qualitative analysis of linear blood flow velocity reveals the decrease in the number of patients with a compensatory reaction in the form of its acceleration in the middle cerebral artery with increasing TBI severity but the number of patients with reduced linear blood flow velocity increases. Abnormal autoregulation of the cerebral circulation and reduction of vascular reactivity was established in the majority of patients of all groups. In addition, the incidence of vascular disturbances increased from 1st to 3rd group. According to the results of rheoencephalography, we detected prevailing spastic changes of the curve in all groups of patients. The degree of disturbances manifestations increases with the severity of TBI.

Demographic mechanisms of inbreeding adjustment through extra-pair reproduction.

Science.gov (United States)

Reid, Jane M; Duthie, A Bradley; Wolak, Matthew E; Arcese, Peter

2015-07-01

One hypothesis explaining extra-pair reproduction is that socially monogamous females mate with extra-pair males to adjust the coefficient of inbreeding (f) of extra-pair offspring (EPO) relative to that of within-pair offspring (WPO) they would produce with their socially paired male. Such adjustment of offspring f requires non-random extra-pair reproduction with respect to relatedness, which is in turn often assumed to require some mechanism of explicit pre-copulatory or post-copulatory kin discrimination. We propose three demographic processes that could potentially cause mean f to differ between individual females' EPO and WPO given random extra-pair reproduction with available males without necessarily requiring explicit kin discrimination. Specifically, such a difference could arise if social pairings formed non-randomly with respect to relatedness or persisted non-randomly with respect to relatedness, or if the distribution of relatedness between females and their sets of potential mates changed during the period through which social pairings persisted. We used comprehensive pedigree and pairing data from free-living song sparrows (Melospiza melodia) to quantify these three processes and hence investigate how individual females could adjust mean offspring f through instantaneously random extra-pair reproduction. Female song sparrows tended to form social pairings with unrelated or distantly related males slightly less frequently than expected given random pairing within the defined set of available males. Furthermore, social pairings between more closely related mates tended to be more likely to persist across years than social pairings between less closely related mates. However, these effects were small and the mean relatedness between females and their sets of potential extra-pair males did not change substantially across the years through which social pairings persisted. Our framework and analyses illustrate how demographic and social structuring within

TEVATRON Searches for Large Extra Dimensions and Leptoquarks

International Nuclear Information System (INIS)

Mattingly, S.

2002-01-01

This paper presents searches for large extra dimensions and leptoquarks in p(anti)p collisions from Run 1 at the Tevatron. Large extra dimensions are searched for in real graviton production with a monojet or monophoton and in virtual graviton exchange processes with electron or photon pairs. Results from leptoquark searches are presented for three generations of leptoquarks. No evidence of signal is found in any searches for large extra dimensions or leptoquarks and limits are placed. Perceptivities for these searches in the Tevatron's Run 2 are discussed and initial Run 2 data is presented. (author)

Extra Molting and Selection on Nymphal Growth in the Desert Locust.

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Benjamin Pélissié

Full Text Available In insects, extra-molting has been viewed as a compensatory mechanism for nymphal growth that contributes to optimize body weight for successful reproduction. However, little is known on the capacity of extra-molting to evolve in natural populations, which limits our understanding of how selection acts on nymphal growth. We used a multi-generational pedigree, individual monitoring and quantitative genetics models to investigate the evolution of extra-molting and its impact on nymphal growth in a solitarious population of the desert locust, Schistocerca gregaria. Growth compensation via extra-molting was observed for 46% of the females, whose adult weight exceeded by 4% that of other females, at a cost of a 22% longer development time. We found a null heritability for body weight threshold only, and the highest and a strongly female-biased heritability for extra molting. Our genetic estimates show that (1 directional selection can act on growth rate, development time and extra-molting to optimize body weight threshold, the target of stabilizing selection, (2 extra-molting can evolve in natural populations, and (3 a genetic conflict, due to sexually antagonistic selection on extra-molting, might prevent its fixation. Finally, we discuss how antagonistic selection between solitarious and gregarious environments and/or genetic correlations between growth and phase traits might also impact the evolution of extra-molting in locusts.

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

Graviton collider effects in one and more large extra dimensions

International Nuclear Information System (INIS)

Giudice, Gian F.; Plehn, Tilman; Strumia, Alessandro

2005-01-01

Astrophysical bounds severely limit the possibility of observing collider signals of gravity with less than 3 flat extra dimensions. However, small distortions of the compactified space can lift the masses of the lightest graviton excitations, evading astrophysical bounds without affecting collider signals of quantum gravity. Following this procedure we reconsider theories with one large extra dimension. A slight space warping gives a model which is safe in the infrared against astrophysical and observational bounds, and which has the ultraviolet properties of gravity with a single flat extra dimension. We extend collider studies to the case of one extra dimension, pointing out its peculiarities. Finally, for a generic number of extra dimensions, we compare different channels in LHC searches for quantum gravity, introducing an ultraviolet cutoff as an additional parameter besides the Planck mass

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.

7 CFR 51.300 - U.S. Extra Fancy.

Science.gov (United States)

2010-01-01

... Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE REGULATIONS AND STANDARDS UNDER THE AGRICULTURAL MARKETING ACT OF 1946... Standards for Grades of Apples Grades § 51.300 U.S. Extra Fancy. “U.S. Extra Fancy” consists of apples of...

Estimation of vascular spaces using radiolabeled erythrocytes

International Nuclear Information System (INIS)

Nasseri, K.

2002-01-01

Measurement of vascular volume is important in many physiological and pathological studies. For isolated organ preparations, this is usually performed using normal erythrocytes (red blood cell; RBC) and in the whole body studies, labeled RBCs are used. The aim of the present project was to compare the two methods in model organ (the liver) in terms of sensitivity and packed RBCs are suspended in normal saline. 100 u l aliquot is injected into the portal vein of rat. The outflow samples collected, hemo lysed and measured by colorimeter. In the second method, the packed RBCs are incubated with Cr-sodium and then resuspended in normal saline. A bolus of labelled RBCs with known activity is injected into portal vein of rats and the outflow activity is determined by gamma spectrometry. The extend of Cr binding to RBCs was investigated; in all experiments less than 2% of the total radioactivity after washing was extra cellular. Both methods were tested in 30 preparations. The normalized frequency outflow profiles of RBCs counted by two methods were then compared. The standard curves of the two methods were also obtained and the correlation was compared. The shape of the curves and calculated vascular volume obtained from the two methods were similar. A good correlation was observed between the methods of measurement of RBCs. The results indicated the second method is more precise and sensitive to low grade changes while the first method is quicker and better preserves RBCs than the second method. Theses advantages, together with safety considerations, favour the first method when it is applicable

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.

Exploring extra dimensions through inflationary tensor modes

Science.gov (United States)

Im, Sang Hui; Nilles, Hans Peter; Trautner, Andreas

2018-03-01

Predictions of inflationary schemes can be influenced by the presence of extra dimensions. This could be of particular relevance for the spectrum of gravitational waves in models where the extra dimensions provide a brane-world solution to the hierarchy problem. Apart from models of large as well as exponentially warped extra dimensions, we analyze the size of tensor modes in the Linear Dilaton scheme recently revived in the discussion of the "clockwork mechanism". The results are model dependent, significantly enhanced tensor modes on one side and a suppression on the other. In some cases we are led to a scheme of "remote inflation", where the expansion is driven by energies at a hidden brane. In all cases where tensor modes are enhanced, the requirement of perturbativity of gravity leads to a stringent upper limit on the allowed Hubble rate during inflation.

Search for Extra Dimensions With ATLAS at LHC

CERN Document Server

Benslama, Kamal

2004-01-01

Theories with extra space time dimensions aiming at resolving the hierarchy problem have recently been developed. These scenarios have provided exciting new grounds for experimental probes. A review of the studies done by the ATLAS collaboration on the sensitivity of the detector to various extra dimension models is reported in this document

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.

Practitioners' Perceptions of the Soccer Extra-Time Period: Implications for Future Research.

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Liam D Harper

Full Text Available Qualitative research investigating soccer practitioners' perceptions can allow researchers to create practical research investigations. The extra-time period of soccer is understudied compared to other areas of soccer research. Using an open-ended online survey containing eleven main and nine sub questions, we gathered the perceptions of extra-time from 46 soccer practitioners, all working for different professional soccer clubs. Questions related to current practices, views on extra-time regulations, and ideas for future research. Using inductive content analysis, the following general dimensions were identified: 'importance of extra-time', 'rule changes', 'efficacy of extra-time hydro-nutritional provision', 'nutritional timing', 'future research directions', 'preparatory modulations' and 'recovery'. The majority of practitioners (63% either agreed or strongly agreed that extra-time is an important period for determining success in knockout football match-play. When asked if a fourth substitution should be permitted in extra-time, 67% agreed. The use of hydro-nutritional strategies prior to extra-time was predominately considered important or very important. However; only 41% of practitioners felt that it was the most important time point for the use of nutritional products. A similar number of practitioners account (50% and do not (50% account for the potential of extra-time when training and preparing players and 89% of practitioners stated that extra-time influences recovery practices following matches. In the five minute break prior to extra-time, the following practices (in order of priority were advocated to players: hydration, energy provision, massage, and tactical preparations. Additionally, 87% of practitioners advocate a particular nutritional supplementation strategy prior to extra-time. In order of importance, practitioners see the following as future research areas: nutritional interventions, fatigue responses, acute injury risk

Practitioners' Perceptions of the Soccer Extra-Time Period: Implications for Future Research.

Science.gov (United States)

Harper, Liam D; Fothergill, Melissa; West, Daniel J; Stevenson, Emma; Russell, Mark

2016-01-01

Qualitative research investigating soccer practitioners' perceptions can allow researchers to create practical research investigations. The extra-time period of soccer is understudied compared to other areas of soccer research. Using an open-ended online survey containing eleven main and nine sub questions, we gathered the perceptions of extra-time from 46 soccer practitioners, all working for different professional soccer clubs. Questions related to current practices, views on extra-time regulations, and ideas for future research. Using inductive content analysis, the following general dimensions were identified: 'importance of extra-time', 'rule changes', 'efficacy of extra-time hydro-nutritional provision', 'nutritional timing', 'future research directions', 'preparatory modulations' and 'recovery'. The majority of practitioners (63%) either agreed or strongly agreed that extra-time is an important period for determining success in knockout football match-play. When asked if a fourth substitution should be permitted in extra-time, 67% agreed. The use of hydro-nutritional strategies prior to extra-time was predominately considered important or very important. However; only 41% of practitioners felt that it was the most important time point for the use of nutritional products. A similar number of practitioners account (50%) and do not (50%) account for the potential of extra-time when training and preparing players and 89% of practitioners stated that extra-time influences recovery practices following matches. In the five minute break prior to extra-time, the following practices (in order of priority) were advocated to players: hydration, energy provision, massage, and tactical preparations. Additionally, 87% of practitioners advocate a particular nutritional supplementation strategy prior to extra-time. In order of importance, practitioners see the following as future research areas: nutritional interventions, fatigue responses, acute injury risk, recovery

Functional paraganglioma extra-adrenal

International Nuclear Information System (INIS)

Arroyo-Martinez, Laura; Alvarez-Pertuz, Humberto; Acuna-Calvo, Jorge; Montoya-Calles, Juan Diego

2006-01-01

Functioning paragangliomas are rare tumours that produce catecholamines.They originate from extra-adrenal chromaffin cells. They are frequently malignant and are associated with high incidence of persistent or recurrent disease after their primary treatment. They are known as glomus, chemodectomas, chromaffin paragangliomas and glomerulocytomas. The location is diverse and reflects the paragangliomar distribution in the body from the base of the skull to the pelvic floor. The paragangliomas are found where there are nodes of the autonomous system, however, approximately 90% of these tumours appear in the adrenal glands (and they constitute the pheochromocytomas) and the remaining 10% is a location extra adrenal, but it has been said that its impact can be underestimated, ranging from 18% to 22% in adults and children up to 30%. The extra-adrenal are originated more frequently in the abdomen (85%), other in the chest (12%) and more rarely in the head and neck (3%). Imaging studies and measurement of non-physiological production of catecholamines may aid in the diagnosis of this entity. Surgery is the treatment of choice. It is presented the case of a primigravidas patient aged 32 with HTAIE requiring caesarean section, who had a postpartum torpid and despite to multiple antihypertensive treatments their pathology was difficult to deal, with ophthalmic complications. Some time later, the patient is studied by hyperhidrosis, laboratory tests and images are requested and it is documented incidentally, a left retroperitoneal tumour, the studies are expanded and reach the correct diagnosis. The tumour required surgical resection. The patient had a satisfactory postoperative period and she discharged with control in the external consultation. (author) [es

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...

Extra Z neutral bosons, families and heavy fermions

International Nuclear Information System (INIS)

Li Tiezhong

1989-08-01

The minimal Grand Unified Theories with three-family should include two extra Z neufral bosons which belong to the different broken scales. Georgi's argument on heavy Dirac fermions has been realized. These fermions should not be bizarre. The extra Z and Dirac fermions are not too heavy. The difficulty of the proton decay may be resolved

a clarification on extra curial statements and hearsay

African Journals Online (AJOL)

MJM Venter

court in Ndhlovu applied section 3 of the Law of Evidence Amendment Act 3 and found that the hearsay extra curial ... law rule, which is that the extra curial statement of an accused (whether an informal admission or a ..... their cellular telephones.38 One patron was assaulted and in the violent gun battle which ensued ...

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

Some Anti-Nutritional and Mineral Contents of Extra-Cotyledonous ...

African Journals Online (AJOL)

The edible extra-cotyledonous deposit of Pride of Barbados (Caesalpina pulcherrima) was investigated for some minerals and antinutritional factors. Results obtained showed that while phytohaemagglutinin was absent, vanadium was very low in the extra-cotyledons of this legume. However, oxalate, trypsin inhibitor, ...

La tuberculose extra-ganglionnaire de la sphere O.R.L. | Mighri ...

African Journals Online (AJOL)

Conclusion : La tuberculose extra-ganglionnaire en ORL pose surtout des problèmes diagnostiques. Son diagnostic est le plus souvent histo-pathologique. Son traitement repose sur la himiothérapie anti-tuberculeuse. Extra-nodal tuberculosis is a rare in ENT practice. We report 10 cases of extra-ganglionic localizations of ...

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.

Vascular anomalies in the mesenteric circulation of patients with Crohn’s disease: a pilot study

Directory of Open Access Journals (Sweden)

Matilde Zamboni

2017-07-01

Full Text Available Crohn’s disease (CD is a chronic inflammatory bowel disease and its pathogenesis is still not well understood. Previous studies suggested the possibility of the involvement of vascular system, but, todate, the mesenteric circulation has poor been investigated, especially in complicated CD cases requiring colectomy. We investigated the mesenteric circulation in a case-control pilot study, including 19 controls and 7 patients affected by complicated cases of CD. Cases and controls underwent selective angiography of both superior and inferior mesenteric district. Transit time was found either significantly shortened in 2/7 cases (29%, or prolonged 5/7 (71% (P=0.0034 in the superior mesenteric district; P=0.0079 in the inferior mesenteric district, respectively due to the presence of A-V malformations and of a miscellaneous of venous abnormalities, which included thrombosis, hypoplasia and extra-truncular venous malformations. Our study demonstrates the presence of congenital or acquired vascular anomalies in a small sample of CD patients not responder to current treatment and with severe complications. The present pilot study warrants further investigations.

Signatures of extra dimensions in gravitational waves

Energy Technology Data Exchange (ETDEWEB)

Andriot, David; Gómez, Gustavo Lucena, E-mail: andriotphysics@gmail.com, E-mail: glucenag@aei.mpg.de [Max-Planck-Institut für Gravitationsphysik, Albert-Einstein-Institut, Am Mühlenberg 1, 14467 Potsdam-Golm (Germany)

2017-06-01

Considering gravitational waves propagating on the most general 4+ N -dimensional space-time, we investigate the effects due to the N extra dimensions on the four-dimensional waves. All wave equations are derived in general and discussed. On Minkowski{sub 4} times an arbitrary Ricci-flat compact manifold, we find: a massless wave with an additional polarization, the breathing mode, and extra waves with high frequencies fixed by Kaluza-Klein masses. We discuss whether these two effects could be observed.

Olive oil compounds inhibit vascular endothelial growth factor receptor-2 phosphorylation

International Nuclear Information System (INIS)

Lamy, Sylvie; Ouanouki, Amira; Béliveau, Richard; Desrosiers, Richard R.

2014-01-01

Vascular endothelial growth factor (VEGF) triggers crucial signaling processes that regulate tumor angiogenesis and, therefore, represents an attractive target for the development of novel anticancer therapeutics. Several epidemiological studies have confirmed that abundant consumption of foods from plant origin is associated with reduced risk of developing cancers. In the Mediterranean basin, the consumption of extra virgin olive oil is an important constituent of the diet. Compared to other vegetable oils, the presence of several phenolic antioxidants in olive oil is believed to prevent the occurrence of a variety of pathological processes, such as cancer. While the strong antioxidant potential of these molecules is well characterized, their antiangiogenic activities remain unknown. The aim of this study is to investigate whether tyrosol (Tyr), hydroxytyrosol (HT), taxifolin (Tax), oleuropein (OL) and oleic acid (OA), five compounds contained in extra virgin olive oil, can affect in vitro angiogenesis. We found that HT, Tax and OA were the most potent angiogenesis inhibitors through their inhibitory effect on specific autophosphorylation sites of VEGFR-2 (Tyr951, Tyr1059, Tyr1175 and Tyr1214) leading to the inhibition of endothelial cell (EC) signaling. Inhibition of VEGFR-2 by these olive oil compounds significantly reduced VEGF-induced EC proliferation and migration as well as their morphogenic differentiation into capillary-like tubular structures in Matrigel. Our study demonstrates that HT, Tax and OA are novel and potent inhibitors of the VEGFR-2 signaling pathway. These findings emphasize the chemopreventive properties of olive oil and highlight the importance of nutrition in cancer prevention. - Highlights: • We investigated five compounds contained in extra virgin olive oil on angiogenesis. • Hydroxytyrosol, taxifolin and oleic acid are the best angiogenesis inhibitors. • Olive oil compounds affect endothelial cell functions essential for

Olive oil compounds inhibit vascular endothelial growth factor receptor-2 phosphorylation

Energy Technology Data Exchange (ETDEWEB)

Lamy, Sylvie, E-mail: lamy.sylvie@uqam.ca; Ouanouki, Amira; Béliveau, Richard; Desrosiers, Richard R.

2014-03-10

Vascular endothelial growth factor (VEGF) triggers crucial signaling processes that regulate tumor angiogenesis and, therefore, represents an attractive target for the development of novel anticancer therapeutics. Several epidemiological studies have confirmed that abundant consumption of foods from plant origin is associated with reduced risk of developing cancers. In the Mediterranean basin, the consumption of extra virgin olive oil is an important constituent of the diet. Compared to other vegetable oils, the presence of several phenolic antioxidants in olive oil is believed to prevent the occurrence of a variety of pathological processes, such as cancer. While the strong antioxidant potential of these molecules is well characterized, their antiangiogenic activities remain unknown. The aim of this study is to investigate whether tyrosol (Tyr), hydroxytyrosol (HT), taxifolin (Tax), oleuropein (OL) and oleic acid (OA), five compounds contained in extra virgin olive oil, can affect in vitro angiogenesis. We found that HT, Tax and OA were the most potent angiogenesis inhibitors through their inhibitory effect on specific autophosphorylation sites of VEGFR-2 (Tyr951, Tyr1059, Tyr1175 and Tyr1214) leading to the inhibition of endothelial cell (EC) signaling. Inhibition of VEGFR-2 by these olive oil compounds significantly reduced VEGF-induced EC proliferation and migration as well as their morphogenic differentiation into capillary-like tubular structures in Matrigel. Our study demonstrates that HT, Tax and OA are novel and potent inhibitors of the VEGFR-2 signaling pathway. These findings emphasize the chemopreventive properties of olive oil and highlight the importance of nutrition in cancer prevention. - Highlights: • We investigated five compounds contained in extra virgin olive oil on angiogenesis. • Hydroxytyrosol, taxifolin and oleic acid are the best angiogenesis inhibitors. • Olive oil compounds affect endothelial cell functions essential for

BOOK REVIEW: Black Holes, Cosmology and Extra Dimensions Black Holes, Cosmology and Extra Dimensions

Science.gov (United States)

Frolov, Valeri P.

2013-10-01

The book Black holes, Cosmology and Extra Dimensions written by Kirill A Bronnikov and Sergey G Rubin has been published recently by World Scientific Publishing Company. The authors are well known experts in gravity and cosmology. The book is a monograph, a considerable part of which is based on the original work of the authors. Their original point of view on some of the problems makes the book quite interesting, covering a variety of important topics of the modern theory of gravity, astrophysics and cosmology. It consists of 11 chapters which are organized in three parts. The book starts with an introduction, where the authors briefly discuss the main ideas of General Relativity, giving some historical remarks on its development and application to cosmology, and mentioning some more recent subjects such as brane worlds, f(R)-theories and gravity in higher dimensions. Part I of the book is called 'Gravity'. Chapters two and three are devoted to the Einstein equations and their spherical symmetric black hole solutions. This material is quite standard and can be found in practically any book on General Relativity. A brief summary of the Kerr metric and black hole thermodynamics are given in chapter four. The main part of this chapter is devoted to spherically symmetric black holes in non-Einstein gravity (with scalar and phantom fields), black holes with regular interior, and black holes in brane worlds. Chapters five and six are mainly dedicated to wormholes and the problem of their stability. Part II (Cosmology) starts with discussion of the Friedmann-Robertson-Walker and de Sitter solutions of the Einstein equations and their properties. It follows by describing a `big picture' of the modern cosmology (inflation, post-inflationary reheating, the radiation-dominated and matter-dominated states, and modern stage of the (secondary) inflation). The authors explain how the inflation models allow one to solve many of the long-standing problems of cosmology, such as

Radiotherapy studies and extra-nodal non-Hodgkin lymphomas, progress and challenges

DEFF Research Database (Denmark)

Specht, L

2012-01-01

Extra-nodal lymphomas may arise in any organ, and different histological subtypes occur in distinct patterns. Prognosis and treatment depend not only on the histological subtype and disease extent, but also on the particular involved extra-nodal organ. The clinical course and response to treatment...... for the more common extra-nodal organs, e.g. stomach, Waldeyer's ring, skin and brain, are fairly well known and show significant variation. A few randomised trials have been carried out testing the role of radiotherapy in these lymphomas. However, for most extra-nodal lymphomas, randomised trials have...... not been carried out, and treatment decisions are made on small patient series and extrapolations from nodal lymphomas. Hopefully, wide international collaboration will make controlled clinical trials possible in the less common extra-nodal lymphomas. Modern highly conformal radiotherapy allows better...

Canonical structure and extra mode of generalized unimodular gravity

Science.gov (United States)

Bufalo, Rodrigo; Oksanen, Markku

2018-02-01

We consider a recently proposed generalization of unimodular gravity, where the lapse function is constrained to be equal to a function of the determinant of the spatial metric f (h ), as a potential origin of a dark fluid with a generally h -dependent equation of state parameter. We establish the Hamiltonian analysis and the canonical path integral for the theory. All the special cases that do not match unimodular gravity involve the violation of general covariance, and consequently the physical content of the theory is changed significantly. Particularly, the case of a constant function f is shown to contain an extra physical degree of freedom in each point of space. Physical consequences of the extra degree of freedom are studied in a linearized theory, where the extra mode is carried by the trace of the metric perturbation. The trace mode does not propagate as a wave, since it satisfies an elliptic partial differential equation in spacetime. Consequently, the trace perturbation is shown to grow exponentially with time, which implies instability. The case of a general f (h ) involves additional second-class constraints, which implies the presence of an extra global degree of freedom that depends only on time (instead of the extra local degree of freedom in the case of a constant f ).

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.

Evidence for extra radiation?

DEFF Research Database (Denmark)

Hamann, J.

2012-01-01

A number of recent analyses of cosmological data have reported hints for the presence of extra radiation beyond the standard model expectation. In order to test the robustness of these claims under different methods of constructing parameter constraints, we perform a Bayesian posterior-based and ......A number of recent analyses of cosmological data have reported hints for the presence of extra radiation beyond the standard model expectation. In order to test the robustness of these claims under different methods of constructing parameter constraints, we perform a Bayesian posterior...... during the marginalisation process, and we demonstrate that the effect is related to the fact that cosmic microwave background (CMB) data constrain N_eff only indirectly via the redshift of matter-radiation equality. Once present CMB data are combined with external information about, e.g., the Hubble...... parameter, the difference between the methods becomes small compared to the uncertainty of N_eff. We conclude that the preference of precision cosmological data for excess radiation is "real" and not an artifact of a specific choice of credible/confidence interval construction....

Exploring the Contribution of Extra Credit in Marketing Education

Science.gov (United States)

Elbeck, Matt; DeLong, Deborah

2015-01-01

This study advances the literature on the incidence, attitudes and motivations to complete extra credit assignments. Behavioral feedback from 59 marketing instructors and 43 Principles of Marketing students aligned with reported incidence rates of offering and completing extra credit assignments, respectively. This was followed with open-ended…

Female bluethroats enhance offspring immunocompetence through extra-pair copulations.

Science.gov (United States)

Johnsen, A; Andersen, V; Sunding, C; Lifjeld, J T

2000-07-20

Female birds frequently copulate with extra-pair males, but the adaptive value of this behaviour is poorly understood. Some studies have suggested that 'good genes' may be involved, where females seek to have their eggs fertilized by high-quality males without receiving any material benefits from them. Nevertheless, it remains to be shown that a genetic benefit is passed on to offspring. Here we report that nestling bluethroats, Luscinia svecica, sired by extra-pair males had a higher T-cell-mediated immune response than their maternal half-siblings raised in the same nest. The difference could not be attributed to nestling body mass, sex or hatching order, but may be an effect of paternal genotype. Extra-pair young were also more immunocompetent than their paternal half-sibs raised in the genetic father's own nest, which indicates an additional effect of maternal genotype. Our results are consistent with the idea that females engage in extra-pair copulations to obtain compatible viability genes, rather than 'good genes' per se.

Extra dimensions and micro black holes at the LHC

International Nuclear Information System (INIS)

Valuev, V.

2009-01-01

Models with extra dimensions have been proposed to solve outstanding problems of the Standard Model. In some of those models the strength of gravity is increased at TeV energies and unified with the electroweak interaction. New studies are presented on the sensitivity to searches for new gauge bosons, such as W' and Z' bosons and other high mass resonances, as predicted e.g. by Randall-Sundrum models; to searches for large (ADD) extra dimensions in channels with missing transverse energy; to searches with di-photon final states; to searches for universal extra dimensions, and to searches for micro black hole production at the LHC. (author)

Pediatric vascular access

International Nuclear Information System (INIS)

Donaldson, James S.

2006-01-01

Pediatric interventional radiologists are ideally suited to provide vascular access services to children because of inherent safety advantages and higher success from using image-guided techniques. The performance of vascular access procedures has become routine at many adult interventional radiology practices, but this service is not as widely developed at pediatric institutions. Although interventional radiologists at some children's hospitals offer full-service vascular access, there is little or none at others. Developing and maintaining a pediatric vascular access service is a challenge. Interventionalists skilled in performing such procedures are limited at pediatric institutions, and institutional support from clerical staff, nursing staff, and technologists might not be sufficiently available to fulfill the needs of such a service. There must also be a strong commitment by all members of the team to support such a demanding service. There is a slippery slope of expected services that becomes steeper and steeper as the vascular access service grows. This review is intended primarily as general education for pediatric radiologists learning vascular access techniques. Additionally, the pediatric or adult interventional radiologist seeking to expand services might find helpful tips. The article also provides education for the diagnostic radiologist who routinely interprets radiographs containing vascular access devices. (orig.)

Physics with large extra dimensions

Indian Academy of Sciences (India)

can then be accounted by the existence of large internal dimensions, in the sub- ... strongly coupled heterotic theory with one large dimension is described by a weakly ..... one additional U(1) factor corresponding to an extra 'U(1)' D-brane is ...

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.

XQCAT eXtra Quark Combined Analysis Tool

CERN Document Server

Barducci, D; Buchkremer, M; Marrouche, J; Moretti, S; Panizzi, L

2015-01-01

XQCAT (eXtra Quark Combined Analysis Tool) is a tool aimed to determine exclusion Confidence Levels (eCLs) for scenarios of new physics characterised by the presence of one or multiple heavy extra quarks (XQ) which interact through Yukawa couplings with any of the Standard Model (SM) quarks. The code uses a database of efficiencies for pre-simulated processes of Quantum Chromo-Dynamics (QCD) pair production and on-shell decays of extra quarks. In the version 1.0 of XQCAT the efficiencies have been computed for a set of seven publicly available search results by the CMS experiment, and the package is subject to future updates to include further searches by both ATLAS and CMS collaborations. The input for the code is a text file in which masses, branching ratios (BRs) and dominant chirality of the couplings of the new quarks are provided. The output of the code is the eCL of the test point for each implemented experimental analysis considered individually and, when possible, in statistical combination.

An Extra Push from Entrance-Channel Effects

International Nuclear Information System (INIS)

Grar, Nabila; Rowley, Neil

2006-01-01

The fusion probability for heavy symmetric systems is known to show certain very specific features. Apart from the large variance of the fusion barrier distribution, it is found that the energy at which the s-wave transmission is 0.5 is shifted to an energy significantly higher than the nominal (e.g. Bass) Coulomb barrier. This last feature is referred to in the literature as the 'extra push' effect. Many models have been devised to explain the origin of these findings. It is worth noting, however, that despite the extra push, the capture cross section is still greatly enhanced at the very lowest energies. This fact cannot be explained within the framework of macroscopic theories involving conditional saddle points or frictional forces. We have performed full coupled-channel calculations for heavy, symmetric systems treating correctly the long-range Coulomb excitations of the collective quadrupole- and octupole-phonon states in the target and projectile. The results obtained show that the extra push and the overall shape of the fusion probability are simply explained by these entrance-channel effects

Transition from galactic to extra-galactic cosmic rays

International Nuclear Information System (INIS)

Aloisio, Roberto

2006-01-01

In this paper we review the main features of the observed Cosmic Rays spectrum in the energy range 10 17 eV to 10 20 eV. We present a theoretical model that explains the main observed features of the spectrum, namely the second Knee and Dip, and implies a transition from Galactic to Extra-Galactic cosmic rays at energy E ≅ 10 18 eV, with a proton dominated Extra-Galactic spectrum

Intersection democracy for winding branes and stabilization of extra dimensions

International Nuclear Information System (INIS)

Rador, Tonguc

2005-01-01

We show that, in the context of pure Einstein gravity, a democratic principle for intersection possibilities of branes winding around extra dimensions in a given partitioning yield stabilization, while what the observed space follows is matter-like dust evolution. Here democracy is used in the sense that, in a given decimation of extra dimensions, all possible wrappings and hence all possible intersections are allowed. Generally, the necessary and sufficient condition for this is that the dimensionality m of the observed space dimensions obey 3= =3, where N is the decimation order of the extra dimensions

Extra Oral Periapical Radiography: A Review

Directory of Open Access Journals (Sweden)

Rachna Kaul

2014-01-01

Full Text Available Background: Intra oral periapical radiographs remain the backbone of diagnostic assessment of dento-facial pathologies. However, in some clinical situation like in developmentally disabled individuals, those with an exaggerated gag reflex, pediatric dental patients and anxious dental patients, it may be very difficult to obtain an intra-oral periapical radiograph of diagnostic quality. In such situations, extra oral periapical radiographs are very useful. They are obtained by placing a sensor outside the oral cavity and then making the radiographic exposure using a digital X ray machine for intra oral radiographs. The radiation dose in this technique is much lesser as compared to panoramic radiographs. This article reviews the technique, advantages, disadvantages and indications of extra oral periapical radiographs.

Vascular Access in Children

International Nuclear Information System (INIS)

Krishnamurthy, Ganesh; Keller, Marc S.

2011-01-01

Establishment of stable vascular access is one of the essential and most challenging procedures in a pediatric hospital. Many clinical specialties provide vascular service in a pediatric hospital. At the top of the “expert procedural pyramid” is the pediatric interventional radiologist, who is best suited and trained to deliver this service. Growing awareness regarding the safety and high success rate of vascular access using image guidance has led to increased demand from clinicians to provide around-the-clock vascular access service by pediatric interventional radiologists. Hence, the success of a vascular access program, with the pediatric interventional radiologist as the key provider, is challenging, and a coordinated multidisciplinary team effort is essential for success. However, there are few dedicated pediatric interventional radiologists across the globe, and also only a couple of training programs exist for pediatric interventions. This article gives an overview of the technical aspects of pediatric vascular access and provides useful tips for obtaining vascular access in children safely and successfully using image guidance.

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...

[Prevalence and risk factors of extra-coronary artery disease in patients with diabetes which confirmed atherosclerosis of coronary arteries].

Science.gov (United States)

Gracheva, S A; Biragova, M S; Glazunova, A M; Klefortova, I I; Melkozerov, K V; Shamkhalova, M Sh; Dzhavelidze, M I; Soldatova, T V; Il'in, A V; Deev, A D; Shestakova, M V; Tugeeva, E F; Buziashvili, Iu I

2014-01-01

To assess prevalence and risk factors of extra-coronary artery disease (peripheral artery (PA) disease (D) of lower extremities (LE), brachiocephalic arterial (BCA) stenosis (S), renal arterial (RA) S in type 1 and 2 (T1 and T2) diabetes (D) patients (P) with confirmed atherosclerosis of coronary arteries (CA). 100 P (48 with T2D, 18 with T1D, 34 without diabetes - PWD), with hemodynamically significant atherosclerosis of CA confirmed by coronary angiography. All patients underwent duplex ultrasonography of PA LE, BCA, RA. Other studies included assessment of clinical characteristics and measurement of the following parameters: profibrogenic cytokines (transforming growth factor [TGF] beta1, matrix metalloproteinase 9 [MMP9], monocyte chemotactic protein-1 [MCP-1], regulated on activation normal T-cell expressed and secreted [RANTES), markers of endothelial dysfunction (von Willebrand factor [VWF], homocystein [HCYST], plasminogen activator inhibitor-1 [PAI-1], vascular cell adhesion molecule [VCAM], soluble intercellular adhesion molecules-1 [sICAM], vascular endothelial growth factor [VEGF], asymmetric dimethylarginine [ADMAD, N-terminal fragment of pro-brain natriuretic peptide (NT-pro BNP), fibroblast growth factor 23 (FGF-23), and fibrinogen. Portions of P with multivessel CA disease were similar in all three groups (T1D - 88.9, T2D - 85.5, WD - 82.3%). Coexistence of atherosclerosis in 2 or more vascular beds was identified in 85.3% of T2D and in 50% of WD P (p = 0.005). In T1D group 61.1 and 11.1% of P had atherosclerosis in 2 and 3 vascular beds, respectively. Levels of profibrogenic cytokines and factors of endothelial activation (RANTES, MMP-9, PAI-I, VCAM, sICAM, ADMA) were significantly higher in P with diabetes vs P WD. P with diabetes and multifocal atherosclerosis demonstrated significant increases of CRP, fibrinogen, NT-proBNP, VWF, PAI-1, ADMA, sICAM, and decrease of GFR compared with P with atherosclerosis in 1 vascular bed. Logistic regression

The Universe’s extra bits

CERN Multimedia

CERN Bulletin

2010-01-01

Parallel universes, unknown forms of matter, extra dimensions….This is not cheap science fiction but very concrete physics theories that the scientists are trying to confirm with the LHC and other ongoing experiments. Although it's enough to make us dream about going to a parallel world for the weekend, let’s keep our feet firmly on the ground and try to work out what all these things really are…   Given the astonishing fact that 96% of the Universe is actually unknown, we can think of filling it with all sorts of weird and exotic things. Extra dimensions and parallel universes may indeed be real, that is, their existence is accepted by a large community of scientists who have worked out mathematical models and physical constraints. “The idea of a fifth dimension was first introduced by Kaluza and Klein at the beginning of the last century in an attempt to unify gravity and electromagnetism”, confirms Ignatios Antoniadis from CERN’s Th...

Oscillation of Angiogenesis and Vascular Dropout in Progressive Human Vascular Disease. [Vascular Pattern as Useful Read-Out of Complex Molecular Signaling

Science.gov (United States)

Parsons-Wingerter, Patricia

2010-01-01

When analyzed by VESsel GENeration Analysis (VESGEN) software, vascular patterns provide useful integrative read-outs of complex, interacting molecular signaling pathways. Using VESGEN, we recently discovered and published our innovative, surprising findings that angiogenesis oscillated with vascular dropout throughout progression of diabetic retinopathy, a blinding vascular disease. Our findings provide a potential paradigm shift in the current prevailing view on progression and treatment of this disease, and a new early-stage window of regenerative therapeutic opportunities. The findings also suggest that angiogenesis may oscillate with vascular disease in a homeostatic-like manner during early stages of other inflammatory progressive diseases such as cancer and coronary vascular disease.

Early pulmonary response is critical for extra-pulmonary carbon nanoparticle mediated effects: comparison of inhalation versus intra-arterial infusion exposures in mice.

Science.gov (United States)

Ganguly, Koustav; Ettehadieh, Dariusch; Upadhyay, Swapna; Takenaka, Shinji; Adler, Thure; Karg, Erwin; Krombach, Fritz; Kreyling, Wolfgang G; Schulz, Holger; Schmid, Otmar; Stoeger, Tobias

2017-06-20

The death toll associated with inhaled ambient particulate matter (PM) is attributed mainly to cardio-vascular rather than pulmonary effects. However, it is unclear whether the key event for cardiovascular impairment is particle translocation from lung to circulation (direct effect) or indirect effects due to pulmonary particle-cell interactions. In this work, we addressed this issue by exposing healthy mice via inhalation and intra-arterial infusion (IAI) to carbon nanoparticles (CNP) as surrogate for soot, a major constituent of (ultrafine) urban PM. Equivalent surface area CNP doses in the blood (30mm 2 per animal) were applied by IAI or inhalation (lung-deposited dose 10,000mm 2 ; accounting for 0.3% of lung-to-blood CNP translocation). Mice were analyzed for changes in hematology and molecular markers of endothelial/epithelial dysfunction, pro-inflammatory reactions, oxidative stress, and coagulation in lungs and extra-pulmonary organs after CNP inhalation (4 h and 24 h) and CNP infusion (4 h). For methodological reasons, we used two different CNP types (spark-discharge and Printex90), with very similar physicochemical properties [≥98 and ≥95% elemental carbon; 10 and 14 nm primary particle diameter; and 800 and 300 m 2 /g specific surface area] for inhalation and IAI respectively. Mild pulmonary inflammatory responses and significant systemic effects were observed following 4 h and 24 h CNP inhalation. Increased retention of activated leukocytes, secondary thrombocytosis, and pro-inflammatory responses in secondary organs were detected following 4 h and 24 h of CNP inhalation only. Interestingly, among the investigated extra-pulmonary tissues (i.e. aorta, heart, and liver); aorta revealed as the most susceptible extra-pulmonary target following inhalation exposure. Bypassing the lungs by IAI however did not induce any extra-pulmonary effects at 4 h as compared to inhalation. Our findings indicate that extra-pulmonary effects due to CNP

Black Holes, Cosmology and Extra Dimensions

International Nuclear Information System (INIS)

Frolov, Valeri P

2013-01-01

Book review: The book Black holes, Cosmology and Extra Dimensions written by Kirill A Bronnikov and Sergey G Rubin has been published recently by World Scientific Publishing Company. The authors are well known experts in gravity and cosmology. The book is a monograph, a considerable part of which is based on the original work of the authors. Their original point of view on some of the problems makes the book quite interesting, covering a variety of important topics of the modern theory of gravity, astrophysics and cosmology. It consists of 11 chapters which are organized in three parts. The book starts with an introduction, where the authors briefly discuss the main ideas of General Relativity, giving some historical remarks on its development and application to cosmology, and mentioning some more recent subjects such as brane worlds, f (R)−theories and gravity in higher dimensions. Part I of the book is called ‘Gravity’. Chapters two and three are devoted to the Einstein equations and their spherical symmetric black hole solutions. Part II (Cosmology) starts with discussion of the Friedmann–Robertson–Walker and de Sitter solutions of the Einstein equations and their properties. Part III covers the material on extra dimensions. It describes how Einstein gravity is modified in the presence of one or more additional spatial dimensions and how these extra dimensions are compactified in the Kaluza–Klein scheme

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

Directory of Open Access Journals (Sweden)

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

[Vascular Calcification - Pathological Mechanism and Clinical Application - . Role of vascular smooth muscle cells in vascular calcification].

Science.gov (United States)

Kurabayashi, Masahiko

2015-05-01

Vascular calcification is commonly seen with aging, chronic kidney disese (CKD), diabetes, and atherosclerosis, and is closely associated with cardiovascular morbidity and mortality. Vascular calcification has long been regarded as the final stage of degeneration and necrosis of arterial wall and a passive, unregulated process. However, it is now known to be an active and tightly regulated process involved with phenotypic transition of vascular smooth muscle cells (VSMC) that resembles bone mineralization. Briefly, calcium deposits of atherosclerotic plaque consist of hydroxyapatite and may appear identical to fully formed lamellar bone. By using a genetic fate mapping strategy, VSMC of the vascular media give rise to the majority of the osteochondrogenic precursor- and chondrocyte-like cells observed in the calcified arterial media of MGP (- / -) mice. Osteogenic differentiation of VSMC is characterized by the expression of bone-related molecules including bone morphogenetic protein (BMP) -2, Msx2 and osteopontin, which are produced by osteoblasts and chondrocytes. Our recent findings are that (i) Runx2 and Notch1 induce osteogenic differentiation, and (ii) advanced glycation end-product (AGE) /receptor for AGE (RAGE) and palmitic acid promote osteogenic differentiation of VSMC. To understand of the molecular mechanisms of vascular calcification is now under intensive research area.

Extra dimensions in space and time

CERN Document Server

Bars, Itzhak

2010-01-01

Covers topics such as Einstein and the Fourth Dimension; Waves in a Fifth Dimension; and String Theory and Branes Experimental Tests of Extra Dimensions. This book offers a discussion on Two-Time Physics

Extra-oral halitosis : an overview

NARCIS (Netherlands)

Tangerman, A.; Winkel, E. G.

Halitosis can be subdivided into intra-oral and extra-oral halitosis, depending on the place where it originates. Most reports now agree that the most frequent sources of halitosis exist within the oral cavity and include bacterial reservoirs such as the dorsum of the tongue, saliva and periodontal

The Resurrection of Jesus: do extra-canonical sources change the landscape?

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F P Viljoen

2005-10-01

Full Text Available The resurrection of Jesus is assumed by the New Testament to be a historical event. Some scholars argue, however, that there was no empty tomb, but that the New Testament accounts are midrashic or mythological stories about Jesus.� In this article extra-canonical writings are investigated to find out what light it may throw on intra-canonical tradition. Many extra-canonical texts seemingly have no knowledge of the passion and resurrection, and such traditions may be earlier than the intra-canonical traditions. Was the resurrection a later invention?� Are intra-canonical texts developments of extra-canonical tradition, or vice versa?� This article demonstrates that extra-canonical texts do not materially alter the landscape of enquiry.

Perceived organizational support and extra-role performance: which leads to which?

Science.gov (United States)

Chen, Zhixia; Eisenberger, Robert; Johnson, Kelly M; Sucharski, Ivan L; Aselage, Justin

2009-02-01

L. Rhoades and R. Eisenberger (2002) reported the meta-analytic finding of a highly statistically significant relation between perceived organizational support (POS) and performance but concluded that the reviewed studies' methodology allowed no conclusion concerning the direction of the association. To investigate this issue, the authors assessed POS and extra-role performance 2 times, separated by a 3-year interval, among 199 employees of an electronic and appliance sales organization. Using a cross-lagged panel design, the authors found that POS was positively associated with a temporal change in extra-role performance. In contrast, the relation between extra-role performance and temporal change in POS was not statistically significant. These findings provide evidence that POS leads to extra-role performance.

Uterine Vascular Lesions

Science.gov (United States)

Vijayakumar, Abhishek; Srinivas, Amruthashree; Chandrashekar, Babitha Moogali; Vijayakumar, Avinash

2013-01-01

Vascular lesions of the uterus are rare; most reported in the literature are arteriovenous malformations (AVMs). Uterine AVMs can be congenital or acquired. In recent years, there has been an increasing number of reports of acquired vascular lesions of the uterus following pregnancy, abortion, cesarean delivery, and curettage. It can be seen from these reports that there is confusion concerning the terminology of uterine vascular lesions. There is also a lack of diagnostic criteria and management guidelines, which has led to an increased number of unnecessary invasive procedures (eg, angiography, uterine artery embolization, hysterectomy for abnormal vaginal bleeding). This article familiarizes readers with various vascular lesions of the uterus and their management. PMID:24340126

Extra dimensions and black hole production

International Nuclear Information System (INIS)

Pagliarona, C.

2001-01-01

This article reviews recent development in models with Large Extra Dimensions and Black hole production at future colliders. Experimental results from current experiments as well as the expectation for the future colliders are summarized

Celulitis por cuerpo extraño

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Miguel B. Carrasco Guzmán

2016-01-01

Full Text Available Las infecciones de la piel y el tejido celular subcutáneo surgen como un grupo importante de afecciones con una alta morbilidad en edades pediátricas, generalmente relacionada con traumatismo y cuerpos extraños. Se presenta el caso de una escolar femenina de 6 años de edad, con síntomas y signos clínicos que sugieren celulitis en el muslo derecho,  por su evolución tórpida se le realizó el estudio ultrasonográfico que confirmó el diagnóstico etiológico de una celulitis secundaria a un traumatismo, provocada por la introducción de un gran cuerpo extraño, que pasó inadvertido para a familia de la menor.

Acute abdomen in children due to extra-abdominal causes.

Science.gov (United States)

Tsalkidis, Aggelos; Gardikis, Stefanos; Cassimos, Dimitrios; Kambouri, Katerina; Tsalkidou, Evanthia; Deftereos, Savas; Chatzimichael, Athanasios

2008-06-01

Acute abdominal pain in children is a common cause for referral to the emergency room and for subsequent hospitalization to pediatric medical or surgical departments. There are rare occasions when the abdominal pain is derived from extra-abdominal organs or systems. The aim of the present study was to establish the most common extra-abdominal causes of acute abdominal pain. The notes of all children (1 month-14 years of age) examined for acute abdominal pain in the Accident and Emergency (A&E) Department of Alexandroupolis District University Hospital in January 2001-December 2005 were analyzed retrospectively. Demographic data, clinical signs and symptoms, and laboratory findings were recorded, as well as the final diagnosis and outcome. Of a total number of 28 124 children who were brought to the A&E department, in 1731 the main complaint was acute abdominal pain. In 51 children their symptoms had an extra-abdominal cause, the most frequent being pneumonia (n = 15), tonsillitis (n = 10), otitis media (n = 9), and acute leukemia (n = 5). Both abdominal and extra-abdominal causes should be considered by a pediatrician who is confronted with a child with acute abdominal pain.

Extra-Anatomic Revascularization of Extensive Coral Reef Aorta.

Science.gov (United States)

Gaggiano, Andrea; Kasemi, Holta; Monti, Andrea; Laurito, Antonella; Maselli, Mauro; Manzo, Paola; Quaglino, Simone; Tavolini, Valeria

2017-10-01

Coral reef aorta (CRA) is a rare, potential lethal disease of the visceral aorta as it can cause visceral and renal infarction. Various surgical approaches have been proposed for the CRA treatment. The purpose of this article is to report different extensive extra-anatomic CRA treatment modalities tailored on the patients' clinical and anatomic presentation. From April 2006 to October 2012, 4 symptomatic patients with extensive CRA were treated at our department. Extra-anatomic aortic revascularization with selective visceral vessels clamping was performed in all cases. Technical success was 100%. No perioperative death was registered. All patients remained asymptomatic during the follow-up period (62, 49, 25, and 94 months, respectively), with bypasses and target vessels patency. The extra-anatomic bypass with selective visceral vessels clamping reduces the aortic occlusion time and the risk of organ ischemia. All approaches available should be considered on a case-by-case basis and in high-volume centers. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

Estrogen, vascular estrogen receptor and hormone therapy in postmenopausal vascular disease.

Science.gov (United States)

Khalil, Raouf A

2013-12-15

Cardiovascular disease (CVD) is less common in premenopausal women than men of the same age or postmenopausal women, suggesting vascular benefits of estrogen. Estrogen activates estrogen receptors ERα, ERβ and GPR30 in endothelium and vascular smooth muscle (VSM), which trigger downstream signaling pathways and lead to genomic and non-genomic vascular effects such as vasodilation, decreased VSM contraction and growth and reduced vascular remodeling. However, randomized clinical trials (RCTs), such as the Women's Health Initiative (WHI) and Heart and Estrogen/progestin Replacement Study (HERS), have shown little vascular benefits and even adverse events with menopausal hormone therapy (MHT), likely due to factors related to the MHT used, ER profile, and RCT design. Some MHT forms, dose, combinations or route of administration may have inadequate vascular effects. Age-related changes in ER amount, distribution, integrity and post-ER signaling could alter the vascular response to MHT. The subject's age, preexisting CVD, and hormone environment could also reduce the effects of MHT. Further evaluation of natural and synthetic estrogens, phytoestrogens, and selective estrogen-receptor modulators (SERMs), and the design of appropriate MHT combinations, dose, route and 'timing' could improve the effectiveness of conventional MHT and provide alternative therapies in the peri-menopausal period. Targeting ER using specific ER agonists, localized MHT delivery, and activation of specific post-ER signaling pathways could counter age-related changes in ER. Examination of the hormone environment and conditions associated with hormone imbalance such as polycystic ovary syndrome may reveal the causes of abnormal hormone-receptor interactions. Consideration of these factors in new RCTs such as the Kronos Early Estrogen Prevention Study (KEEPS) could enhance the vascular benefits of estrogen in postmenopausal CVD. Copyright © 2013 Elsevier Inc. All rights reserved.

The vascular surgery workforce: a survey of consultant vascular surgeons in the UK, 2014.

Science.gov (United States)

Harkin, D W; Beard, J D; Shearman, C P; Wyatt, M G

2015-04-01

The purpose of this study was to describe the demographics, training, and practice characteristics of consultant vascular surgeons across the UK to provide an assessment of current, and inform future prediction of workforce needs. A questionnaire was developed using a modified Delphi process to generate questionnaire items. The questionnaire was emailed to all consultant vascular surgeons (n = 450) in the UK who were members of the Vascular Society of Great Britain & Ireland. 352 consultant vascular surgeons from 95 hospital trusts across the UK completed the survey (78% response rate). The mean age was 50.6 years old, the majority (62%) were mid-career, but 24% were above the age of 55. Currently, 92% are men and only 8% women. 93% work full-time, with 60% working >50 hours, and 21% working >60 hours per week. The average team was 5 to 6 (range 2-10) vascular surgeons, with 23% working in a large team of ≥8. 17% still work in small teams of ≤3. Over 90% of consultant vascular surgeons perform the major index vascular surgery procedures (aneurysm repair, carotid endarterectomy, infra-inguinal bypass, amputation). While 84% perform standard endovascular abdominal aortic aneurysm repair (EVAR), <50% perform more complex endovascular aortic therapy. The majority of vascular surgeons "like their job" (85%) and are "satisfied" (69%) with their job. 34% of consultant vascular surgeons indicated they were "extremely likely" to retire within the next 10 years. This study provides the first detailed analysis of the new specialty of vascular surgery as practiced in the UK. There is a need to plan for a significant expansion in the consultant vascular surgeon workforce in the UK over the next 10 years to maintain the status quo. Copyright © 2014 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Extra generations and discrepancies of electroweak precision data

OpenAIRE

Novikov, V. A.; Okun, L. B.; Rozanov, A. N.; Vysotsky, M. I.

2001-01-01

It is shown that additional chiral generations are not excluded by the latest electroweak precision data if one assumes that there is no mixing with the known three generations. In the case of ``heavy extra generations'', when all four new particles are heavier than $Z$ boson, quality of the fit for the one new generation is as good as for zero new generations (Standard Model). In the case of neutral leptons with masses around 50 GeV (``partially heavy extra generations'') the minimum of $\\ch...

Extra-Articular Manifestations of Seronegative and Seropositive Rheumatoid Arthritis

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Vjollca Sahatçiu-Meka

2010-02-01

Full Text Available Although considered a “joint disease,” rheumatoid arthritis is associated with the involvement of extra-articular manifestations. The aim of the study is the investigation and comparison of frequency and type of extra-articular manifestations in a well defined community based cohort of patients with seropositive and seronegative rheumatoid arthritis. Using the ACR (1987 criteria for rheumatoid arthritis, patients have been classified into the 2nd and 3rd functional class (ARA. The studied group consisted of 125 seronegative patients with titters lower than 1:64 as defined by Rose-Waaler test, whereas the control group consisted of 125 seropositive patients with titters of 1:64 or higher. All patients were between 25-60 years of age (Xb=49,96, with disease duration between 1-27 years (Xb=6,41. In order to present the findings of the study, the structure, prevalence, arithmetic mean (Xb, standard deviation (SB, variation quotient (QV% and variation interval (Rmax-Rmin have been used. Probability level has been expressed by p<0,01 and p<0,05. Correlation between the number of extra-articular manifestations and duration of the disease has been calculated by means of Pearson linear correlation. Higher presence of diffuse lung fibrosis, central and peripheral nervous system damages have been confirmed in the seropositive group, and osteoporosis in the seronegative; however, no statistical difference has been found. In extra-articular manifestations, “rheumatoid core” in the seropositive subset (χ2=4,80, p<0,05 presented significant statistical difference. Rheumatoid nodules were more frequent in seropositive subset (12%:16%, in both sexes; however, they were not of significant statistical difference. Neuropathy and lung diseases were also frequently present in seropositive group, but no statistical difference has been found regarding the statistical difference. Longer duration of the disease resulted in an increase of the number of extra

Extra-articular manifestations of seronegative and seropositive rheumatoid arthritis.

Science.gov (United States)

Sahatciu-Meka, Vjollca; Rexhepi, Sylejman; Manxhuka-Kerliu, Suzana; Rexhepi, Mjellma

2010-02-01

Although considered a "joint disease," rheumatoid arthritis is associated with the involvement of extra-articular manifestations. The aim of the study is the investigation and comparison of frequency and type of extra-articular manifestations in a well defined community based cohort of patients with seropositive and seronegative rheumatoid arthritis. Using the ACR (1987) criteria for rheumatoid arthritis, patients have been classified into the 2nd and 3rd functional class (ARA). The studied group consisted of 125 seronegative patients with titters lower than 1:64 as defined by Rose-Waaler test, whereas the control group consisted of 125 seropositive patients with titters of 1:64 or higher. All patients were between 25-60 years of age (Xb=49,96), with disease duration between 1-27 years (Xb=6,41). In order to present the findings of the study, the structure, prevalence, arithmetic mean (Xb), standard deviation (SB), variation quotient (QV%) and variation interval (Rmax-Rmin) have been used. Probability level has been expressed by p<0,01 and p<0,05. Correlation between the number of extra-articular manifestations and duration of the disease has been calculated by means of Pearson linear correlation. Higher presence of diffuse lung fibrosis, central and peripheral nervous system damages have been confirmed in the seropositive group, and osteoporosis in the seronegative; however, no statistical difference has been found. In extra-articular manifestations, "rheumatoid core" in the seropositive subset (chi2=4,80, p<0,05) presented significant statistical difference. Rheumatoid nodules were more frequent in seropositive subset (12%:16%), in both sexes; however, they were not of significant statistical difference. Neuropathy and lung diseases were also frequently present in seropositive group, but no statistical difference has been found regarding the statistical difference. Longer duration of the disease resulted in an increase of the number of extra

Building on comparative experience : the Venezuelan extra-heavy crude oil projects

International Nuclear Information System (INIS)

Valentine, T.E.

2004-01-01

This paper reviewed legal considerations regarding heavy and extra heavy oil production in both Canada and Venezuela. The paper focused on Venezuela's extra heavy oil projects in the Orinoco Oil Belt, one of the world's largest accumulation of bitumen with an estimated reserve of 1.2 trillion barrels. The paper described the following four projects: the Petrozuata, Cerro Negro, SINCOR, and Hamaca heavy oil projects which are all congressionally approved joint ventures for extra-heavy crudes in the Orinoco Belt. It also described the legal regime which governs heavy oil projects in Venezuela, including the Organic Gaseous Hydrocarbon Law and the Organic Hydrocarbon Law. Twenty congressional conditions which have been imposed were also outlined along with the legal considerations and lessons learned regarding new extra-heavy crude projects under the two legal regimes. 1 fig

VEGFR tyrosine kinase inhibitor II (VRI) induced vascular insufficiency in zebrafish as a model for studying vascular toxicity and vascular preservation

International Nuclear Information System (INIS)

Li, Shang; Dang, Yuan Ye; Oi Lam Che, Ginny; Kwan, Yiu Wa; Chan, Shun Wan; Leung, George Pak Heng; Lee, Simon Ming Yuen; Hoi, Maggie Pui Man

2014-01-01

In ischemic disorders such as chronic wounds and myocardial ischemia, there is inadequate tissue perfusion due to vascular insufficiency. Besides, it has been observed that prolonged use of anti-angiogenic agents in cancer therapy produces cardiovascular toxicity caused by impaired vessel integrity and regeneration. In the present study, we used VEGFR tyrosine kinase inhibitor II (VRI) to chemically induce vascular insufficiency in zebrafish in vivo and human umbilical vein endothelial cells (HUVEC) in vitro to further study the mechanisms of vascular morphogenesis in these pathological conditions. We also explored the possibility of treating vascular insufficiency by enhancing vascular regeneration and repair with pharmacological intervention. We observed that pretreatment of VRI induced blood vessel loss in developing zebrafish by inhibiting angiogenesis and increasing endothelial cell apoptosis, accompanied by down-regulation of kdr, kdrl and flt-1 genes expression. The VRI-induced blood vessel loss in zebrafish could be restored by post-treatment of calycosin, a cardiovascular protective isoflavone. Similarly, VRI induced cytotoxicity and apoptosis in HUVEC which could be rescued by calycosin post-treatment. Further investigation of the underlying mechanisms showed that the PI3K/AKT/Bad cell survival pathway was a main contributor of the vascular regenerative effect of calycosin. These findings indicated that the cardiovascular toxicity in anti-angiogenic therapy was mainly caused by insufficient endothelial cell survival, suggesting its essential role in vascular integrity, repair and regeneration. In addition, we showed that VRI-induced blood vessel loss in zebrafish represented a simple and effective in vivo model for studying vascular insufficiency and evaluating cancer drug vascular toxicities. - Highlights: • In vivo VRI model • Rescue effects of calycosin • Calycosin EC survival pathways

Non-Alcoholic Fatty Liver Disease and Extra-Hepatic Cancers

Directory of Open Access Journals (Sweden)

Claudia Sanna

2016-05-01

Full Text Available Non-alcoholic fatty liver disease (NAFLD is a leading cause of chronic liver disease but the second cause of death among NAFLD patients are attributed to malignancies at both gastrointestinal (liver, colon, esophagus, stomach, and pancreas and extra-intestinal sites (kidney in men, and breast in women. Obesity and related metabolic abnormalities are associated with increased incidence or mortality for a number of cancers. NAFLD has an intertwined relationship with metabolic syndrome and significantly contributes to the risk of hepatocellular carcinoma (HCC, but recent evidence have fuelled concerns that NAFLD may be a new, and added, risk factor for extra-hepatic cancers, particularly in the gastrointestinal tract. In this review we critically appraise key studies on NAFLD-associated extra-hepatic cancers and speculate on how NAFLD may influence carcinogenesis at these sites.

Extra-oral Appliances in Orthodontic Treatment.

Science.gov (United States)

Almuzian, Mohammed; Alharbi, Fahad; McIntyre, Grant

2016-01-01

Extra-oral appliances are used in orthodontics to apply forces to the jaws, dentition or both and the popularity of these appliances is cyclical. Although the use of retraction headgear for the management of Class II malocclusion has declined over the last 20 years with the refinement of non-compliance approaches, including temporary anchorage devices, headgear still has a useful role in orthodontics. The use of protraction headgear has increased as more evidence of its effectiveness for the treatment of Class lIl malocclusion has become available. This paper describes the mechanics and contemporary uses of headgear in orthodontics for primary care dentists and specialist orthodontists. CPD/CLINICAL RELEVANCE: Extra-oral appliances have specific uses in orthodontic biomechanics. Clinicians using retraction headgear and protraction headgear should be familiar with their clinical indications, the potential problems and how these can be avoided.

Extra-Curricular Social Studies in an Open Air History Museum

Science.gov (United States)

Morris, Ronald Vaughan

2008-01-01

This article discusses extra-curricular social studies in an Open Air History Museum. Open Air History Museum, Conner Prairie Interpretive Park in Fishers, Indiana, is a cultural institution that encourages and supports talented students as they participate in an extra-curricular program. Ten-to sixteen-year-old youths "apply for jobs"…

Vascular pattern formation in plants.

Science.gov (United States)

Scarpella, Enrico; Helariutta, Ykä

2010-01-01

Reticulate tissue systems exist in most multicellular organisms, and the principles underlying the formation of cellular networks have fascinated philosophers, mathematicians, and biologists for centuries. In particular, the beautiful and varied arrangements of vascular tissues in plants have intrigued mankind since antiquity, yet the organizing signals have remained elusive. Plant vascular tissues form systems of interconnected cell files throughout the plant body. Vascular cells are aligned with one another along continuous lines, and vascular tissues differentiate at reproducible positions within organ environments. However, neither the precise path of vascular differentiation nor the exact geometry of vascular networks is fixed or immutable. Several recent advances converge to reconcile the seemingly conflicting predictability and plasticity of vascular tissue patterns. A control mechanism in which an apical-basal flow of signal establishes a basic coordinate system for body axis formation and vascular strand differentiation, and in which a superimposed level of radial organizing cues elaborates cell patterns, would generate a reproducible tissue configuration in the context of an underlying robust, self-organizing structure, and account for the simultaneous regularity and flexibility of vascular tissue patterns. Copyright 2010 Elsevier Inc. All rights reserved.

Breast metastases primitive extra mammary

International Nuclear Information System (INIS)

Terzieff, V.; Vázquez, A.; Alonso, I.; Sabini, G.

2004-01-01

Less than 3% of all breast cancers originate from a primitive extra mammary. In 40% of cases it is the first manifestation of the primitive properly studied but 80% are associated with widely disseminated disease. It typically presents as a nodule on external quadrant s painful in half the cases. The majority (60%) of metastases derived from breast contralateral breast tumors are believed to via the lymphatic system. of the ; extra mammary the most common tumors are melanoma; hematologic and neuroendocrine. Although some imaging characteristics can guide diagnosis is histological. Cytology has good performance in experienced hands; but up to 25% of cases there may be difficulty in establishing diagnosis. Treatment depends on the type of tumor. Mastectomy should not be practiced or axillary clearance routine as is generally the context of disease disseminated. Radiation therapy may be useful for local control. It has been proposed laser ablation but no experience with it. The overall prognosis is bad. For a man of 45 with a breast metastasis occurs only a clear cell carcinoma of the kidney

Implementing a citizen's DWI reporting program using the Extra Eyes model

Science.gov (United States)

2008-09-01

This manual is a guide for law enforcement agencies and community organizations in creating and implementing a citizens DWI reporting program in their communities modeling the Operation Extra Eyes program. Extra Eyes is a program that engages volu...

Practitioners' Perceptions of the Soccer Extra-Time Period: Implications for Future Research

OpenAIRE

Harper, Liam D.; Fothergill, Melissa; West, Daniel J.; Stevenson, Emma; Russell, Mark

2016-01-01

Qualitative research investigating soccer practitioners’ perceptions can allow researchers to create practical research investigations. The extra-time period of soccer is understudied compared to other areas of soccer research. Using an open-ended online survey containing eleven main and nine sub questions, we gathered the perceptions of extra-time from 46 soccer practitioners, all working for different professional soccer clubs. Questions related to current practices, views on extra-time reg...

Deviations from Newton's law in supersymmetric large extra dimensions

International Nuclear Information System (INIS)

Callin, P.; Burgess, C.P.

2006-01-01

Deviations from Newton's inverse-squared law at the micron length scale are smoking-gun signals for models containing supersymmetric large extra dimensions (SLEDs), which have been proposed as approaches for resolving the cosmological constant problem. Just like their non-supersymmetric counterparts, SLED models predict gravity to deviate from the inverse-square law because of the advent of new dimensions at sub-millimeter scales. However SLED models differ from their non-supersymmetric counterparts in three important ways: (i) the size of the extra dimensions is fixed by the observed value of the dark energy density, making it impossible to shorten the range over which new deviations from Newton's law must be seen; (ii) supersymmetry predicts there to be more fields in the extra dimensions than just gravity, implying different types of couplings to matter and the possibility of repulsive as well as attractive interactions; and (iii) the same mechanism which is purported to keep the cosmological constant naturally small also keeps the extra-dimensional moduli effectively massless, leading to deviations from general relativity in the far infrared of the scalar-tensor form. We here explore the deviations from Newton's law which are predicted over micron distances, and show the ways in which they differ and resemble those in the non-supersymmetric case

Effects of albumin administration in serum liver enzymes of rats in the presence of extrahepatic biliary obstruction Efeitos da administração de albumina nos níveis séricos de enzimas hepáticas em ratos com obstrução biliar extra-hepática

Directory of Open Access Journals (Sweden)

Jorge Fernando Rebouças Lessa

2011-01-01

Full Text Available PURPOSE: To study the influence of albumin on changes of liver function in the extrahepatic biliary obstruction through an experimental model in rats. METHODS: Sixty rats were divided into four groups: Group C (Control: 6 animals. Group M (Fictitious Operation: 18 rats underwent laparotomy and handling of the bile ducts; Groups O (extrahepatic biliary obstruction and A (Treated with 2% albumin: 18 animals in each group underwent ligation of the ductus liver; The animals in groups M, O and A were divided into three subgroups of 6 animals each to be killed in the 7, 14 and 21 days postoperative (POD. Blood was drawn for determination of total bilirubin (TB, indirect bilirubin (IB, direct bilirubin (DB, alkaline phosphatase (ALP, aspartate aminotransferase (AST and alanine aminotransferase (ALT. RESULTS: On POD 7, BI levels were 4.5 mg / dl in group O and 2.1 mg / dl in group A (p = 0.025. On the 14th POD, the levels of PA were 1185.2 U / l in the group and O 458.3 U / l in group A (p = 0.004. ALT levels were 101.7 U / l in the group O and 75.7 U / l in group A (= 0.037. On POD 21, the levels of ALP were 1069.5 U / l in the group O and 468.3 U / l in group A (p = 0, 004. CONCLUSION: The administration of albumin reduced the serum levels of bilirubin in the 7th day of supplementationOBJETIVO: Estudar a influência da albumina em alterações funcionais do fígado na obstrução biliar extra-hepática por meio de um modelo experimental desenvolvido em ratos. MÉTODOS: 60 ratos distribuídos em quatro grupos: Grupo C (Controle: 6 animais. Grupo M (Operação Fictícia: 18 ratos submetidos à laparotomia e manuseio das vias biliares; Grupos O (Obstrução Biliar Extra-hepática e A (Tratados com albumina a 2%: 18 animais, em cada grupo, submetidos à ligadura do ducto hepático; Os animais dos grupos M, O e A foram distribuídos em três subgrupos de 6 animais cada, para serem mortos nos 7°, 14° e 21° dias pós- operatórios (DPO. Foi colhido sangue

The Formulation of Extra-Territorial Recognition

Czech Academy of Sciences Publication Activity Database

Hrubec, Marek

2010-01-01

Roč. 1, č. 1 (2010), s. 65-72 ISSN 1674-1277 R&D Projects: GA MŠk(CZ) LC06013 Institutional research plan: CEZ:AV0Z90090514 Keywords : global justice * extra-territorial recognition Subject RIV: AA - Philosophy ; Religion

Differential diagnosis of extra-axial intracranial tumours by dynamic spin-echo MRI