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Sample records for celleskade ved bilirubin

  1. Bilirubin - urine

    MedlinePlus

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

  2. Bilirubin Test

    MedlinePlus

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

  3. Bilirubin - blood

    MedlinePlus

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

  4. Blood Test: Bilirubin

    MedlinePlus

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

  5. [Cytoprotective effects of bilirubin].

    PubMed

    Vítek, L

    2005-01-01

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

  6. Inherited Disorders of Bilirubin Clearance

    PubMed Central

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

    2016-01-01

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

  7. Optical transcutaneous bilirubin detector

    DOEpatents

    Kronberg, James W.

    1993-01-01

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

  8. Optical transcutaneous bilirubin detector

    DOEpatents

    Kronberg, J.W.

    1991-03-04

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

  9. Optical transcutaneous bilirubin detector

    DOEpatents

    Kronberg, J.W.

    1993-11-09

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

  10. Bilirubin measurements in neonates

    NASA Astrophysics Data System (ADS)

    Newman, Gregory J.

    2000-04-01

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

  11. Bilirubin present in diverse angiosperms

    PubMed Central

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

    2010-01-01

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

  12. The Biological Effects of Bilirubin Photoisomers.

    PubMed

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

    2016-01-01

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

  13. Bilirubin Binding Capacity in the Preterm Neonate.

    PubMed

    Amin, Sanjiv B

    2016-06-01

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

  14. Photoacoustic microscopy of bilirubin in tissue phantoms

    NASA Astrophysics Data System (ADS)

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

    2012-12-01

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

  15. The Biological Effects of Bilirubin Photoisomers

    PubMed Central

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

    2016-01-01

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

  16. Bilirubin Binding to PPARα Inhibits Lipid Accumulation.

    PubMed

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

    2016-01-01

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

  17. Bilirubin Binding to PPARα Inhibits Lipid Accumulation

    PubMed Central

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

    2016-01-01

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

  18. Bilirubin and Its Carbohydrate Conjugates

    NASA Astrophysics Data System (ADS)

    Blanckaert, Norbert J. C.

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

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

    PubMed

    Amin, Sanjiv B

    2004-10-01

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

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

    PubMed Central

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

    1968-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2007-06-01

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

  2. Universal bilirubin screening for severe neonatal hyperbilirubinemia.

    PubMed

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

    2010-10-01

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

  3. PPARα: A Master Regulator of Bilirubin Homeostasis.

    PubMed

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

    2014-01-01

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

  4. Initial photochemistry of bilirubin probed by femtosecond spectroscopy.

    PubMed

    Zietz, Burkhard; Gillbro, Tomas

    2007-10-18

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

  5. Alteration of serum bilirubin level in schizophrenia.

    PubMed

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

    2010-11-01

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

  6. Mechanisms of bilirubin toxicity: clinical implications.

    PubMed

    Hansen, Thor Willy Ruud

    2002-12-01

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

  7. Can Excess Bilirubin Levels Cause Learning Difficulties?

    ERIC Educational Resources Information Center

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

    2002-01-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  10. Bilirubin-Induced Neurotoxicity in the Preterm Neonate.

    PubMed

    Watchko, Jon F

    2016-06-01

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

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

    SciTech Connect

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

    1988-07-01

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

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

    PubMed

    Babin, Steven M; Sova, Raymond M

    2014-01-01

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

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

    PubMed Central

    Babin, Steven M; Sova, Raymond M

    2014-01-01

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

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

    PubMed

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

    1975-08-01

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

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

    PubMed

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

    2014-11-01

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

  16. Bilirubin and its oxidation products damage brain white matter

    PubMed Central

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

    2014-01-01

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

  17. Enzymic oxidation of unconjugated bilirubin by rat liver.

    PubMed Central

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

    1986-01-01

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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  19. Conjugated Bilirubin Triggers Anemia by Inducing Erythrocyte Death

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2016-06-20

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

  1. In Cellulo Mapping of Subcellular Localized Bilirubin.

    PubMed

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

    2016-08-19

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

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

    PubMed

    Mahram, Manoochehr; Oveisi, Sonia; Jaberi, Najmeh

    2015-12-01

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

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

    PubMed

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

    2014-01-01

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

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

    PubMed

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

    2014-04-01

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

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

    PubMed Central

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

    2015-01-01

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

  6. Bilirubin Neurotoxicity in Preterm Infants: Risk and Prevention

    PubMed Central

    Bhutani, Vinod K.; Wong, Ronald J.

    2013-01-01

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

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

    PubMed

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

    2008-08-01

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

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

    PubMed Central

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

    1978-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2012-03-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed

    Mano, Nicolas; Edembe, Lise

    2013-12-15

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

  13. Bilirubin-Induced Audiologic Injury in Preterm Infants.

    PubMed

    Olds, Cristen; Oghalai, John S

    2016-06-01

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

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

    PubMed

    Matsudo, T; Saitoh, T; Matsubara, C

    2001-02-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed

    Kirk, Jean M

    2008-09-01

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

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

    PubMed

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

    2016-08-16

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

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

    PubMed

    Gopi, Manigandan; Seshadri, Mandalam Subramanian

    2016-04-01

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

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

    PubMed Central

    Seshadri, Mandalam Subramanian

    2016-01-01

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

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

    ERIC Educational Resources Information Center

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

    2006-01-01

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

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

    PubMed

    Vítek, Libor; Ostrow, J Donald

    2009-01-01

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

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

    PubMed

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

    2015-09-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2011-01-01

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

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

    PubMed Central

    Billing, B H

    1978-01-01

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

  5. Multistimuli-Responsive Bilirubin Nanoparticles for Anticancer Therapy.

    PubMed

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

    2016-08-26

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

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

    PubMed Central

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

    2009-01-01

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

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

    PubMed

    Mustafa, Mir Faisal; Bano, Bilqees

    2014-05-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    1977-01-01

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

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

    PubMed Central

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

    1977-01-01

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

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

    PubMed

    Van Molle, W; Libert, C

    2003-08-01

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

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

    Code of Federal Regulations, 2011 CFR

    2011-04-01

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

  13. 21 CFR 862.1113 - Bilirubin (total and unbound) in the neonate test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

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

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

    Code of Federal Regulations, 2010 CFR

    2010-04-01

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

  15. 21 CFR 862.1113 - Bilirubin (total and unbound) in the neonate test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

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

  16. 21 CFR 862.1113 - Bilirubin (total and unbound) in the neonate test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

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

  17. 21 CFR 862.1115 - Urinary bilirubin and its conjugates (nonquantitative) test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

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

  18. 21 CFR 862.1113 - Bilirubin (total and unbound) in the neonate test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

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

  19. 21 CFR 862.1115 - Urinary bilirubin and its conjugates (nonquantitative) test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

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

  20. 21 CFR 862.1113 - Bilirubin (total and unbound) in the neonate test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

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

  1. 21 CFR 862.1115 - Urinary bilirubin and its conjugates (nonquantitative) test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed

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

    2015-05-01

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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    PubMed

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

    2016-04-21

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

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

    PubMed

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

    2001-01-01

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

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

    PubMed

    Celier, C; Foliot, A

    1984-04-01

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

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

    PubMed Central

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

    1982-01-01

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

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

    ERIC Educational Resources Information Center

    Rubin, Rosalyn A.; And Others

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

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

    PubMed Central

    Stremmel, W; Berk, P D

    1986-01-01

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

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

    PubMed Central

    Ostrow, J Donald; Mukerjee, Pasupati

    2007-01-01

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

  12. Metabolism of bilirubin by human cytochrome P450 2A6

    SciTech Connect

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

    2012-05-15

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

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

    PubMed

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

    1978-02-01

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

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

    PubMed Central

    Hartmann, F; Bissell, D M

    1982-01-01

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

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

    PubMed

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

    2014-01-01

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

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

    SciTech Connect

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

    1991-03-01

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

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

    PubMed Central

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

    2009-01-01

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

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

    PubMed

    Rohmer, Thierry; Matysik, Jörg; Mark, Franz

    2011-10-27

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    1992-05-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-02-01

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

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

    PubMed Central

    Levitt, David G; Levitt, Michael D

    2014-01-01

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

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

    PubMed

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

    2013-01-01

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

  5. Life and consciousness - The Vedāntic view.

    PubMed

    Shanta, Bhakti Niskama

    2015-01-01

    In the past, philosophers, scientists, and even the general opinion, had no problem in accepting the existence of consciousness in the same way as the existence of the physical world. After the advent of Newtonian mechanics, science embraced a complete materialistic conception about reality. Scientists started proposing hypotheses like abiogenesis (origin of first life from accumulation of atoms and molecules) and the Big Bang theory (the explosion theory for explaining the origin of universe). How the universe came to be what it is now is a key philosophical question. The hypothesis that it came from Nothing (as proposed by Stephen Hawking, among others), proves to be dissembling, since the quantum vacuum can hardly be considered a void. In modern science, it is generally assumed that matter existed before the universe came to be. Modern science hypothesizes that the manifestation of life on Earth is nothing but a mere increment in the complexity of matter - and hence is an outcome of evolution of matter (chemical evolution) following the Big Bang. After the manifestation of life, modern science believed that chemical evolution transformed itself into biological evolution, which then had caused the entire biodiversity on our planet. The ontological view of the organism as a complex machine presumes life as just a chance occurrence, without any inner purpose. This approach in science leaves no room for the subjective aspect of consciousness in its attempt to know the world as the relationships among forces, atoms, and molecules. On the other hand, the Vedāntic view states that the origin of everything material and nonmaterial is sentient and absolute (unconditioned). Thus, sentient life is primitive and reproductive of itself - omne vivum ex vivo - life comes from life. This is the scientifically verified law of experience. Life is essentially cognitive and conscious. And, consciousness, which is fundamental, manifests itself in the gradational forms of all

  6. Life and consciousness – The Vedāntic view

    PubMed Central

    Shanta, Bhakti Niskama

    2015-01-01

    In the past, philosophers, scientists, and even the general opinion, had no problem in accepting the existence of consciousness in the same way as the existence of the physical world. After the advent of Newtonian mechanics, science embraced a complete materialistic conception about reality. Scientists started proposing hypotheses like abiogenesis (origin of first life from accumulation of atoms and molecules) and the Big Bang theory (the explosion theory for explaining the origin of universe). How the universe came to be what it is now is a key philosophical question. The hypothesis that it came from Nothing (as proposed by Stephen Hawking, among others), proves to be dissembling, since the quantum vacuum can hardly be considered a void. In modern science, it is generally assumed that matter existed before the universe came to be. Modern science hypothesizes that the manifestation of life on Earth is nothing but a mere increment in the complexity of matter — and hence is an outcome of evolution of matter (chemical evolution) following the Big Bang. After the manifestation of life, modern science believed that chemical evolution transformed itself into biological evolution, which then had caused the entire biodiversity on our planet. The ontological view of the organism as a complex machine presumes life as just a chance occurrence, without any inner purpose. This approach in science leaves no room for the subjective aspect of consciousness in its attempt to know the world as the relationships among forces, atoms, and molecules. On the other hand, the Vedāntic view states that the origin of everything material and nonmaterial is sentient and absolute (unconditioned). Thus, sentient life is primitive and reproductive of itself – omne vivum ex vivo – life comes from life. This is the scientifically verified law of experience. Life is essentially cognitive and conscious. And, consciousness, which is fundamental, manifests itself in the gradational forms of all

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

    Kunutsor, Setor K

    2015-12-01

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

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

    NASA Astrophysics Data System (ADS)

    Alla, Suresh K.

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

    Kim, Sung Young; Park, Sang Chul

    2012-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2016-06-01

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

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

    PubMed

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

    2008-01-18

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

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed

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

    2016-07-01

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

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

    PubMed

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

    2016-05-01

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

  18. A Content Analysis of the VEDS Data Collection and Reporting Procedures Used by the 57 State Boards for Vocational Education.

    ERIC Educational Resources Information Center

    Russo, Rocco P.

    Congress, using Public Law 94-482 entitled Education Amendments of 1976, instructed the National Center for Education Statistics (NCES) to develop, implement, and operate the Vocational Education Data System (VEDS). As mandated by legislation, the primary purpose of VEDS is to provide a national reporting system to generate uniform data from the…

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2007-01-01

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

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

    PubMed Central

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

    1978-01-01

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

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

    PubMed

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

    2016-05-01

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

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

    PubMed Central

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

    1975-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2008-05-01

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

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

    PubMed

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

    2007-04-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed

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

    2016-09-01

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

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

    PubMed

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

    2013-12-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2012-07-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

    Crigler, John F.; Gold, Norman I.

    1969-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2001-09-01

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

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

    PubMed

    Orlov, Sergey; Goncharova, Iryna; Urbanová, Marie

    2014-05-21

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

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

    PubMed

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

    2016-06-01

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

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

    Code of Federal Regulations, 2012 CFR

    2012-04-01

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

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

    Code of Federal Regulations, 2014 CFR

    2014-04-01

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

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

    Code of Federal Regulations, 2013 CFR

    2013-04-01

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

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

    Code of Federal Regulations, 2010 CFR

    2010-04-01

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

  3. 21 CFR 862.1110 - Bilirubin (total or direct) test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

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

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

    PubMed

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

    2015-03-01

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

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

    PubMed

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

    2014-11-15

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

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

    PubMed

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

    1994-05-01

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

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

    PubMed Central

    Vítek, Libor

    2012-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed

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

    2016-02-01

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

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

    PubMed

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

    2015-11-15

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

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

    SciTech Connect

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

    2011-11-15

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

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

    PubMed

    Davis, D R; Yeary, R A

    1980-02-01

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

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

    PubMed

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

    2016-05-01

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

  15. ABC and VED Analysis of the Pharmacy Store of a Tertiary Care Teaching, Research and Referral Healthcare Institute of India.

    PubMed

    Devnani, M; Gupta, Ak; Nigah, R

    2010-04-01

    The ABC and VED (vital, essential, desirable) analysis of the pharmacy store of Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India, was conducted to identify the categories of items needing stringent management control. The annual consumption and expenditure incurred on each item of pharmacy for the year 2007-08 was analyzed and inventory control techniques, i.e. ABC, VED and ABC-VED matrix analysis, were applied. The drug formulary of the pharmacy consisted of 421 items. The total annual drug expenditure (ADE) on items issued in 2007-08 was Rs. 40,012,612. ABC analysis revealed 13.78%, 21.85% and 64.37% items as A, B and C category items, respectively, accounting for 69.97%, 19.95% and 10.08% of ADE of the pharmacy. VED analysis showed 12.11%, 59.38% and 28.51% items as V, E, and D category items, respectively, accounting for 17.14%, 72.38% and 10.48% of ADE of the pharmacy. On ABC-VED matrix analysis, 22.09%, 54.63% and 23.28% items were found to be category I, II and III items, respectively, accounting for 74.21%, 22.23% and 3.56% of ADE of the pharmacy. The ABC and VED techniques need to be adopted as a routine practice for optimal use of resources and elimination of out-of-stock situations in the hospital pharmacy. PMID:21264126

  16. Performance of viscoelastic dampers (VED) under various temperatures and application of magnetorheological dampers (MRD) for seismic control of structures

    NASA Astrophysics Data System (ADS)

    Bhatti, Abdul Qadir

    2013-08-01

    A number of studies have been carried out to investigate the performance of viscoelastic dampers (VEDs) and magnetorheological dampers (MRDs) in controlling the seismic response of buildings, but very few of them regarding the effect of temperature on the behavior of those dampers. The energy absorption properties of the VEDs are dependent on the ambient temperature, excitation frequency and strain amplitude. Several mathematical models have been investigated for reproducing the experimental behavior of single degree of freedom VEDs and MEDs. Of these, only the fractional derivative model can reflect the influence of temperature which is, however, so complex that it is difficult to apply in structural analysis. In order to verify the effect of temperature, two case studies of structural element have been conducted: once using VED and once using MRD. Kelvin-Voigt mathematical model applied, they were investigated and after analyzing the results, the force vs. displacement showed that MRD achieved a high force capacity and a better performance than VED. Furthermore, the effect of the temperature in case of VED observed via plotting the dissipated energy hysteresis at different temperatures. These results validate the effect of the temperature as the lower the temperature the more viscous the dashpot element becomes, hence improving damping, but this is up to a specific low temperature.

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

    PubMed

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

    2012-10-01

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

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

    PubMed

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

    2015-11-16

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

  19. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) increases bilirubin formation but hampers quantitative hepatic conversion of biliverdin to bilirubin in rats with wild-type AH receptor.

    PubMed

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

    2014-06-01

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

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

    PubMed

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

    2005-08-01

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

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

    PubMed Central

    Jansen, Thomas; Daiber, Andreas

    2012-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

    Ricci, G L; Fevery, J

    1989-01-01

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

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

    PubMed

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

    2012-11-01

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

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

    PubMed Central

    Maksinovic, Rada; Ketin, Sonja; Biocanin, Rade

    2015-01-01

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

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

    PubMed

    Call, N B; Tisher, C C

    1975-02-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

    Kaplan, D; Navon, G

    1982-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  11. Terahertz-Regime, Micro-VEDs: Evaluation of Micromachined TWT Conceptual Designs

    NASA Technical Reports Server (NTRS)

    Booske, John H.; Kory, Carol L.; Gallagher, D.; van der Weide, Daniel W.; Limbach, S; Gustafson, P; Lee, W.-J.; Gallagher, S.; Jain, K.

    2001-01-01

    Summary form only given. The Terahertz (THz) region of the electromagnetic spectrum (approx.300-3000 GHz) has enormous potential for high-data-rate communications, spectroscopy, astronomy, space research, medicine, biology, surveillance, remote sensing, industrial process control, etc. The most critical roadblock to full exploitation of the THz band is lack of coherent radiation sources that are powerful (0.01-10.0 W continuous wave), efficient (>1 %), frequency agile (instantaneously tunable over 1% bandwidths or more), reliable, and relatively inexpensive. Micro-machined Vacuum Electron Devices (micro-VEDs) represent a promising solution. We describe prospects for miniature, THz-regime TWTs fabricated using micromachining techniques. Several approx.600 GHz conceptual designs are compared. Their expected performance has been analyzed using SD, 2.51), and 3D TWT codes. A folded waveguide (FWG) TWT forward-wave amplifier design is presented based on a Northrop Grumman (NGC) optimized design procedure. This conceptual device is compared to the simulated performance of a novel, micro-VED helix TWT. Conceptual FWG TWT backward-wave amplifiers and oscillators are also discussed. A scaled (100 GHz) FWG TWT operating at a relatively low voltage (-12 kV) is under development at NGC. Also, actual-size micromachining experiments are planned to evaluate the feasibility of arrays of micro-VED TWTs. Progress and results of these efforts are described. This work was supported, in part by AFOSR, ONR, and NSF.

  12. Vedāntic view of life: Reply to Gustavo Caetano-Anollés

    PubMed Central

    2016-01-01

    ABSTRACT The author would like to thank Professor Gustavo Caetano-Anollés from Department of Crop Sciences, University of Illinois for his interest in his work. We may sometimes observe that there is a noticeable difference between the anecdote people narrate about the implications of a scientific paper and the real conclusion of the paper. Prof. Gustavo Caetano-Anollés's response1 is an ideal example of the same, where he has tried to make great hay about the implications of the article “Life and consciousness – The Vedāntic view.”2 The Vedāntic view subscribes neither to the views of ‘Creationist Movement’/‘Intelligent Design’, nor it supports some splendid anti-science proposal. Vedāntic view refutes the dominant reductionistic view of life in modern biology by proposing a viable alternative concept of ‘Organic Whole’ and thus serves a scientific critique to the nescience (avidyā) that is practiced on the name of science. PMID:27195069

  13. Vedāntic view of life: Reply to Gustavo Caetano-Anollés.

    PubMed

    Shanta, Bhakti Niskama

    2016-01-01

    The author would like to thank Professor Gustavo Caetano-Anollés from Department of Crop Sciences, University of Illinois for his interest in his work. We may sometimes observe that there is a noticeable difference between the anecdote people narrate about the implications of a scientific paper and the real conclusion of the paper. Prof. Gustavo Caetano-Anollés's response(1) is an ideal example of the same, where he has tried to make great hay about the implications of the article "Life and consciousness - The Vedāntic view."(2) The Vedāntic view subscribes neither to the views of 'Creationist Movement'/'Intelligent Design', nor it supports some splendid anti-science proposal. Vedāntic view refutes the dominant reductionistic view of life in modern biology by proposing a viable alternative concept of 'Organic Whole' and thus serves a scientific critique to the nescience (avidyā) that is practiced on the name of science. PMID:27195069

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2015-04-01

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

  16. Feasibility Study of Impact of the Proposed National Vocational Education Data Reporting and Accounting System (VEDS) Forms on Reporting Systems for Secondary Vocational Education in Wisconsin. Project Report.

    ERIC Educational Resources Information Center

    Poehlmann, M. M.

    A study was conducted to determine the feasibility of implementing a reporting system, the National Vocational Education Reporting and Accounting System (VEDS), for secondary vocational education in Wisconsin. As proposed by the National Center for Educational Statistics, the VEDS system is a comprehensive information collection package to provide…

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

    SciTech Connect

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

    2015-01-01

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

  18. Consciousness, Cognition and the Cognitive Apparatus in the Vedānta Tradition

    PubMed Central

    Balasubramanian, R.

    2011-01-01

    A human being is a complex entity consisting of the Self (also known as Consciousness), mind, senses and the body. The Vedānta tradition holds that the mind, the senses and the body are essentially different from the Self or Consciousness. It is through consciousness that we are able to know the things of the world, making use of the medium of the mind and the senses. Furthermore, the mind, though material, is able to reveal things, borrowing the light from consciousness. From the phenomenological point of view, we have to answer the following questions: how does one know the mind/the mental operations/the cogitations of the mind? Does the mind know itself? Is it possible? There is, again, the problem of the intentionality of consciousness. Is consciousness intentional? According to Vedānta, consciousness by its very nature is not intentional, but it becomes intentional through the mind. The mind or the ego is not part of the consciousness; on the contrary, it is transcendent to consciousness. It is difficult to spell out the relation between consciousness and the mind. How does consciousness, which is totally different from the mind, get related to the mind in such a way that it makes the latter capable of comprehending the things of the world? The Vedānta tradition provides the answer to this question in terms of the knower-known relation. Consciousness is pure light, self-luminous by its very nature, that is, although it reveals other objects, it is not revealed by anything else. When Sartre describes it as nothingness, bereft of even ego, it is to show that it is pure light revealing objects outside it. PMID:21694962

  19. Consciousness, cognition and the cognitive apparatus in the vedānta tradition.

    PubMed

    Balasubramanian, R

    2011-01-01

    A human being is a complex entity consisting of the Self (also known as Consciousness), mind, senses and the body. The Vedānta tradition holds that the mind, the senses and the body are essentially different from the Self or Consciousness. It is through consciousness that we are able to know the things of the world, making use of the medium of the mind and the senses. Furthermore, the mind, though material, is able to reveal things, borrowing the light from consciousness. From the phenomenological point of view, we have to answer the following questions: how does one know the mind/the mental operations/the cogitations of the mind? Does the mind know itself? Is it possible? There is, again, the problem of the intentionality of consciousness. Is consciousness intentional? According to Vedānta, consciousness by its very nature is not intentional, but it becomes intentional through the mind. The mind or the ego is not part of the consciousness; on the contrary, it is transcendent to consciousness. It is difficult to spell out the relation between consciousness and the mind. How does consciousness, which is totally different from the mind, get related to the mind in such a way that it makes the latter capable of comprehending the things of the world? The Vedānta tradition provides the answer to this question in terms of the knower-known relation. Consciousness is pure light, self-luminous by its very nature, that is, although it reveals other objects, it is not revealed by anything else. When Sartre describes it as nothingness, bereft of even ego, it is to show that it is pure light revealing objects outside it. PMID:21694962

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

    PubMed

    Zipursky, Alvin; Bhutani, Vinod K

    2015-02-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2014-11-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2016-09-01

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

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

    PubMed

    Lamola, Angelo A; Russo, Marie

    2014-01-01

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

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

    PubMed Central

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

    1998-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2015-07-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed

    Alvarez, C; Strumia, M; Bertorello, H

    2001-10-30

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

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

    PubMed Central

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

    2010-01-01

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

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

    PubMed Central

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

    1995-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

    Kuenzle, Clive C.

    1970-01-01

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

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

    PubMed

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

    2016-03-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2016-05-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed

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

    2016-06-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2004-07-01

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

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

    PubMed

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

    2016-11-01

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

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

    PubMed

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

    2016-04-01

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

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

    PubMed

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

    2009-08-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2004-11-01

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

  7. A Comparison of Community College Responders and Non-Responders to the VEDS Student Follow-Up Survey.

    ERIC Educational Resources Information Center

    Carifio, James; And Others

    In September 1984, a Vocational Education Data System (VEDS) follow-up survey was conducted of all 5,267 students who had graduated from Massachusetts public community colleges in 1982-83. Of these graduates, 1,881 (35.7%) returned the survey, and 3,386 (64.3%) did not. A subsequent study was conducted to compare the characteristics of survey…

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

    NASA Astrophysics Data System (ADS)

    King, Angela G.

    2009-08-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

    Zhang, Lei; Jin, Gu

    2005-07-01

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

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

    PubMed

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

    2016-05-15

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

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

    PubMed

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

    2016-07-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2002-08-01

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

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

    PubMed

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

    2016-10-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    SciTech Connect

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

    2013-08-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2007-07-01

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

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

    PubMed

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

    1999-09-01

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

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

    PubMed Central

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

    2016-01-01

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

  1. Heme Degradation by Heme Oxygenase Protects Mitochondria but Induces ER Stress via Formed Bilirubin

    PubMed Central

    Müllebner, Andrea; Moldzio, Rudolf; Redl, Heinz; Kozlov, Andrey V.; Duvigneau, J. Catharina

    2015-01-01

    Heme oxygenase (HO), in conjunction with biliverdin reductase, degrades heme to carbon monoxide, ferrous iron and bilirubin (BR); the latter is a potent antioxidant. The induced isoform HO-1 has evoked intense research interest, especially because it manifests anti-inflammatory and anti-apoptotic effects relieving acute cell stress. The mechanisms by which HO mediates the described effects are not completely clear. However, the degradation of heme, a strong pro-oxidant, and the generation of BR are considered to play key roles. The aim of this study was to determine the effects of BR on vital functions of hepatocytes focusing on mitochondria and the endoplasmic reticulum (ER). The affinity of BR to proteins is a known challenge for its exact quantification. We consider two major consequences of this affinity, namely possible analytical errors in the determination of HO activity, and biological effects of BR due to direct interaction with protein function. In order to overcome analytical bias we applied a polynomial correction accounting for the loss of BR due to its adsorption to proteins. To identify potential intracellular targets of BR we used an in vitro approach involving hepatocytes and isolated mitochondria. After verification that the hepatocytes possess HO activity at a similar level as liver tissue by using our improved post-extraction spectroscopic assay, we elucidated the effects of increased HO activity and the formed BR on mitochondrial function and the ER stress response. Our data show that BR may compromise cellular metabolism and proliferation via induction of ER stress. ER and mitochondria respond differently to elevated levels of BR and HO-activity. Mitochondria are susceptible to hemin, but active HO protects them against hemin-induced toxicity. BR at slightly elevated levels induces a stress response at the ER, resulting in a decreased proliferative and metabolic activity of hepatocytes. However, the proteins that are targeted by BR still have

  2. Heme oxygenase-1 induction prevents neuronal damage triggered during mitochondrial inhibition: role of CO and bilirubin.

    PubMed

    Orozco-Ibarra, Marisol; Estrada-Sánchez, Ana María; Massieu, Lourdes; Pedraza-Chaverrí, José

    2009-06-01

    Heme oxygenase (HO) catalyzes the breakdown of heme to iron, carbon monoxide (CO), and biliverdin, the latter being further reduced to bilirubin (BR). A protective role of the inducible isoform, HO-1, has been described in pathological conditions associated with reactive oxygen species (ROS) and oxidative damage. The aim of this study was to investigate the role of HO-1 in the neurotoxicity induced by the mitochondrial toxin 3-nitropropionic acid (3-NP) in primary cultures of cerebellar granule neurons (CGNs). Toxicity of 3-NP is associated with ROS production, and this metabolic toxin has been used to mimic pathological conditions such as Huntington's disease. We found that cell death caused by 3-NP exposure was exacerbated by inhibition of HO with tin mesoporphyrin (SnMP). In addition, HO-1 up-regulation induced by the exposure to cobalt protoporphyrin (CoPP) before the incubation with 3-NP, prevented the cell death and the increase in ROS induced by 3-NP. Interestingly, addition of SnMP to CoPP-pretreated CGNs exposed to 3-NP, abolished the protective effect of CoPP suggesting that HO activity was responsible for this protective effect. This was additionally supported by the fact that CORM-2, a CO-releasing molecule, and BR, were able to protect against cell death and the increase in ROS induced by 3-NP. Our data clearly show that HO-1 elicits in CGNs a neuroprotective action against the neurotoxicity of 3-NP and that CO and BR may be involved, at least in part, in this protective effect. The present results increase our knowledge about the role of HO-1 in neuropathological conditions. PMID:19063990

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

    PubMed Central

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

    2016-01-01

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

  4. Grasping at ontological straws: overcoming reductionism in the Advaita Vedānta-Neuroscience dialogue.

    PubMed

    Kaplan, Stephen

    2009-01-01

    Contemporary neuropsychology reveals that the parietal lobe contains neurons that are specifically attuned to the act of grasping and this act may be fundamental to the establishment of the phenomenal boundaries between subject and object. Furthermore, alterations to this process, such as the hypoactivation of this region during meditation or the hyperactivation associated with schizophrenia, may eliminate or confuse, respectively, the phenomenal boundaries between subject and object. Traversing disciplines, the Advaita Vedānta school of Hinduism traces some of its key terms for subject and object to the verbal root grah, to grasp. The subject is literally the grasper. Furthermore, the practice of asparśa yoga, the yoga of no-touch, is aimed at stopping, hypoactivating, the grasping process in order to transcend all subject-object boundaries. This paper will argue that while we have not uncovered an identity of thought, we have uncovered a confluence of ideas between these two disciplines. We will see that this confluence of ideas has not pitted the believer against the critic-not forced us into the great reductionism debate that has dominated so much of the interchange between religious studies and the sciences. This case study will illuminate some of the methodological ways around this reductionism battle and also the boundaries of both disciplines for the intellectual benefit of each. PMID:20681086

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

    PubMed Central

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

    2014-01-01

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

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

    SciTech Connect

    Kim, Sangsoo Daniel; Antenos, Monica; Squires, E. James; Kirby, Gordon M.

    2013-07-15

    Bilirubin (BR) has recently been identified as the first endogenous substrate for cytochrome P450 2A5 (CYP2A5) and it has been suggested that CYP2A5 plays a major role in BR clearance as an alternative mechanism to BR conjugation by uridine-diphosphate glucuronyltransferase 1A1. This study investigated the mechanisms of Cyp2a5 gene regulation by BR and the cytoprotective role of CYP2A5 in BR hepatotoxicity. BR induced CYP2A5 expression at the mRNA and protein levels in a dose-dependent manner in primary mouse hepatocytes. BR treatment also caused nuclear translocation of Nuclear factor-E2 p45-related factor 2 (Nrf2) in hepatocytes. In reporter assays, BR treatment of primary hepatocytes transfected with a Cyp2a5 promoter-luciferase reporter construct resulted in a 2-fold induction of Cyp2a5 reporter activity. Furthermore, cotransfection of the hepatocytes with a Nrf2 expression vector without BR treatment resulted in an increase in Cyp2a5 reporter activity of approximately 2-fold and BR treatment of Nrf2 cotransfectants further increased reporter activity by 4-fold. In addition, site-directed mutation of the ARE in the reporter construct completely abolished both the BR- and Nrf2-mediated increases in reporter activity. The cytoprotective role of CYP2A5 against BR-mediated apoptosis was also examined in Hepa 1–6 cells that lack endogenous CYP2A5. Transient overexpression of CYP2A5 partially blocked BR-induced caspase-3 cleavage in Hepa 1–6 cells. Furthermore, in vitro degradation of BR was increased by microsomes from Hepa 1–6 cells overexpressing CYP2A5 compared to control cells transfected with an empty vector. Collectively, these results suggest that Nrf2-mediated CYP2A5 transactivation in response to BR may provide an additional mechanism for adaptive cytoprotection against BR hepatotoxicity. - Highlights: • The mechanism of Cyp2a5 gene regulation by BR was investigated. • The cytoprotective role of CYP2A5 in BR hepatotoxicity was determined. • BR

  7. Thymoquinone, an active constituent of Nigella sativa seeds, binds with bilirubin and protects mice from hyperbilirubinemia and cyclophosphamide-induced hepatotoxicity.

    PubMed

    Laskar, Amaj A; Khan, Masood A; Rahmani, Arshad H; Fatima, Sana; Younus, Hina

    2016-08-01

    Some reports indicate that thymoquinone (TQ), the main constituent of Nigella sativa seeds, is hepatoprotective. The aim of this study was to determine whether TQ is able to bind directly to bilirubin, and whether TQ or liposomal formulation of TQ (Lip-TQ) can reduce cyclophosphamide (CYP)-induced liver toxicity, serum bilirubin level in mice. The binding of TQ with bilirubin was studied by UV-VIS, fluorescence and Near-UV CD spectroscopy. Inhibition of binding of bilirubin to erythrocytes by TQ was also examined. To increase the in vivo efficacy, Lip-TQ was prepared and used against CYP-induced toxicity. The protective role of TQ or Lip-TQ against CYP-induced toxicity was assessed by determining the liver function parameters, the levels of superoxide dismutase (SOD) and catalase (CAT), and histological studies. It was found that TQ binds to bilirubin and significantly inhibits the binding of bilirubin to erythrocytes. Lip-TQ (10 mg/kg) significantly reduced the levels of aspartate transaminase (AST) from 254 ± 48 to 66 ± 18 IU/L (P < 0.001), alanine transaminase (ALT) from 142 ± 28 to 47.8 ± 16 IU/L (P < 0.05) and serum bilirubin from 2.8 ± 0.50 to 1.24 ± 0.30 mg/dl (P < 0.05). Treatment with Lip-TQ reduced the CYP-induced inflammation and hemorrhage in liver tissues. Moreover, treatment with free or Lip-TQ protected the activity of SOD and CAT in CYP-injected mice. Therefore, TQ can reduce the level of bilirubin in systemic circulation in disease conditions that lead to hyperbilirubinemia and liver toxicity and hence may be used as a supplement in the treatment of liver ailments. PMID:27265787

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

    PubMed Central

    Tasca, Federico; Farias, Diego; Castro, Carmen; Acuna-Rougier, Cristina; Antiochia, Riccarda

    2015-01-01

    The oxygen reduction reaction is one of the most important chemical processes in energy converting systems and living organisms. Mediator-less, direct electro-catalytic reduction of oxygen to water was achieved on spectrographite electrodes modified by physical adsorption of bilirubin oxidases from Myrothecium verrucaria. The existence of an alternative resting form of the enzyme is validated. The effect on the catalytic cycle of temperature, pH and the presence of halogens in the buffer was investigated. Previous results on the electrochemistry of bilirubin oxidase and on the impact of the presence of halogens are reviewed and reinterpreted. PMID:26196288

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

    PubMed Central

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

    2015-01-01

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

  10. Polymer resins with amino acid containing pendants for sorption of bilirubin. II. Polyamide resins with various basic amino acids.

    PubMed

    Henning, D S; Brown, G R; St-Pierre, L E

    1986-01-01

    Short peptides, three to eight amino acids in length, containing various combinations of alanine, arginine, lysine, histidine and tyrosine have been synthesized onto water-swellable polyamide resin by the solid phase peptide synthesis method. The amount of bilirubin adsorbed from aqueous buffer solution (pH = 7.8) by the resins increases with increasing basicity of the amino acids in the pendant. As the number of basic amino acids on the pendant is increased from one to five a 4.7 fold enhancement in the adsorption capacity is seen for arginine while a 9.3 fold enhancement is obtained for lysine. A corresponding increase in length for the non-basic histidine results in a 6 fold enhancement. With alanine the adsorption capacity is uneffected by an increase in pendant length. PMID:3957453

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

    PubMed Central

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

    2015-01-01

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

  12. Increasing the catalytic activity of Bilirubin oxidase from Bacillus pumilus: Importance of host strain and chaperones proteins.

    PubMed

    Gounel, Sébastien; Rouhana, Jad; Stines-Chaumeil, Claire; Cadet, Marine; Mano, Nicolas

    2016-07-20

    Aggregation of recombinant proteins into inclusion bodies (IBs) is the main problem of the expression of multicopper oxidase in Escherichia coli. It is usually attributed to inefficient folding of proteins due to the lack of copper and/or unavailability of chaperone proteins. The general strategies reported to overcome this issue have been focused on increasing the intracellular copper concentration. Here we report a complementary method to optimize the expression in E. coli of a promising Bilirubin oxidase (BOD) isolated from Bacillus pumilus. First, as this BOD has a disulfide bridge, we switched E.coli strain from BL21 (DE3) to Origami B (DE3), known to promote the formation of disulfide bridges in the bacterial cytoplasm. In a second step, we investigate the effect of co-expression of chaperone proteins on the protein production and specific activity. Our strategy allowed increasing the final amount of enzyme by 858% and its catalytic rate constant by 83%. PMID:27165502

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

    PubMed Central

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

    2010-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-09-01

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

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

    PubMed Central

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

    2016-01-01

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

  17. Endogenously elevated bilirubin modulates kidney function and protects from circulating oxidative stress in a rat model of adenine-induced kidney failure

    PubMed Central

    Boon, Ai-Ching; Lam, Alfred K.; Gopalan, Vinod; Benzie, Iris F.; Briskey, David; Coombes, Jeff S.; Fassett, Robert G.; Bulmer, Andrew C.

    2015-01-01

    Mildly elevated bilirubin is associated with a reduction in the presence and progression of chronic kidney disease and related mortality, which may be attributed to bilirubin’s antioxidant properties. This study investigated whether endogenously elevated bilirubin would protect against adenine-induced kidney damage in male hyperbilirubinaemic Gunn rats and littermate controls. Animals were orally administered adenine or methylcellulose solvent (vehicle) daily for 10 days and were then monitored for 28 days. Serum and urine were assessed throughout the protocol for parameters of kidney function and antioxidant/oxidative stress status and kidneys were harvested for histological examination upon completion of the study. Adenine-treated animals experienced weight-loss, polyuria and polydipsia; however, these effects were significantly attenuated in adenine-treated Gunn rats. No difference in the presence of dihydroadenine crystals, lymphocytic infiltration and fibrosis were noted in Gunn rat kidneys versus controls. However, plasma protein carbonyl and F2-isoprostane concentrations were significantly decreased in Gunn rats versus controls, with no change in urinary 8-oxo-7,8-dihydro-2′-deoxyguanosine or kidney tissue F2-isoprostane concentrations. These data indicated that endogenously elevated bilirubin specifically protects from systemic oxidative stress in the vascular compartment. These data may help to clarify the protective relationship between bilirubin, kidney function and cardiovascular mortality in clinical investigations. PMID:26498893

  18. Developmental onset of bilirubin-induced neurotoxicity involves Toll-like receptor 2-dependent signaling in humanized UDP-glucuronosyltransferase1 mice.

    PubMed

    Yueh, Mei-Fei; Chen, Shujuan; Nguyen, Nghia; Tukey, Robert H

    2014-02-21

    Biological and signaling events that connect developmentally induced hyperbilirubinemia to bilirubin-induced neurological dysfunction (BIND) and CNS toxicity in humans are poorly understood. In mammals, UDP-glucuronosyltransferase 1A1 (UGT1A1) is the sole enzyme responsible for bilirubin glucuronidation, a rate-limiting step necessary for bilirubin metabolism and clearance. Humanized mice that express the entire UGT1 locus (hUGT1) and the UGT1A1 gene, develop neonatal hyperbilirubinemia, with 8-10% of hUGT1 mice succumbing to CNS damage, a phenotype that is presented by uncontrollable seizures. We demonstrate that neuroinflammation and reactive gliosis are prominent features of bilirubin brain toxicity, and a disturbed redox status resulting from activation of NADPH oxidase is an important contributing mechanism found in BIND. Using knock-out mice and primary brain cells, we connect a key pattern recognition receptor, Toll-like receptor 2 (TLR2), to hyperbilirubinemia-induced signaling. We illustrate a requirement for TLR2 signaling in regulating gliosis, proinflammatory mediators, and oxidative stress when neonatal mice encounter severe hyperbilirubinemia. TLR2-mediated gliosis strongly correlates with pronounced neuroinflammation in the CNS with up-regulation of TNFα, IL-1β, and IL-6, creating a pro-inflammatory CNS environment. Gene expression and immunohistochemistry staining show that hUGT1/Tlr2(-/-) mice fail to activate glial cells, proinflammatory cytokines, and stress response genes. In addition, bilirubin-induced apoptosis was significantly enhanced by blocking TLR2 signaling indicating its anti-apoptotic property. Consequently, a higher neonatal death rate (57.1%) in hUGT1/Tlr2(-/-) mice was observed when compared with hUGT1 mice (8.7%). These results suggest that TLR2 signaling and microglia neuroinflammation are linked to a repair and/or protection mode against BIND. PMID:24403077

  19. Substrate recycling scheme for tetrachloro-p-benzoquinone using bilirubin oxidase and NADH: Application for pentachlorophenol assay

    SciTech Connect

    Cybulski, D.; Luong, J.H.T.; Male, K.B.; Scharer, J.M.; Moo-Young, M.

    1999-03-01

    A novel assay for tetrachloro-p-benzoquinone (TCBQ), the main oxidation product of pentachlorophenol (PCP), was developed using bilirubin oxidase (BOX) in the presence of excess NADH. TCBQ was easily and rapidly reduced by NADH to 1,4-tetrachlorohydroquinone (TCHQ), which was then recycled back to TCBQ by the enzyme. BOX exhibited no reactivity toward NADH while its catalytic activity for the oxidation of TCHQ was very high. Under an optimized condition, the rate of NADH consumption determined by measuring the absorbance decrease at 340 nm yielded a detection limit for TCBQ of 110 nM. Fluorescence detection of the NADH using a lower enzyme concentration with excitation and emission wavelengths of 345 and 450 nm, respectively, allowed for a TCBQ detection limit of 30 nM. PCP was oxidized to TCBQ with high yield using bis(trifluoroacetoxy)iodobenzene in 0.05 M trichloroacetic acid. Coupling this oxidation reaction to the BOX/NADH assay attained PCT detection limits of 170 and 50 nM using absorbance and fluorescence measurements, respectively. When tested on PCP-contaminated soil samples, the BOX assay compared very well with HPLC measurements.

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

    NASA Astrophysics Data System (ADS)

    Rakshit, Rupali; Pal, Monalisa; Chaudhuri, Arka; Mandal, Madhuri; Mandal, Kalyan

    2015-11-01

    Herein, we report an unprecedented bilirubin (BR) adsorption efficiency of CoFe2O4 (CFO) nanostructures in contrast to the commercially available activated carbon and resin which are generally used for haemoperfusion and haemodialysis. We have synthesized CFO nanoparticles of diameter 100 nm and a series of nano-hollow spheres of diameter 100, 160, 250, and 350 nm using a simple template free solvothermal technique through proper variation of reaction time and capping agent, oleylamine (OLA), respectively, and carried out SiO2 coating by employing Stöber method. The comparative BR adsorption study of CFO and SiO2 coated CFO nanostructures indicates that apart from porosity and hollow configuration of nanostructures, the electrostatic affinity between anionic carboxyl group of BR and cationic amine group of OLA plays a significant role in adsorbing BR. Finally, we demonstrate that the BR adsorption capacity of the nanostructures can be tailored by varying the morphology as well as size of the nanostructures. We believe that our developed magnetic nanostructures could be considered as a potential material towards therapeutic applications against hyperbilirubinemia.

  1. How the Intricate Interactions between Carbon Nanotubes and Two Bilirubin Oxidases Control Direct and Mediated O2 Reduction.

    PubMed

    Mazurenko, Ievgen; Monsalve, Karen; Rouhana, Jad; Parent, Philippe; Laffon, Carine; Goff, Alan Le; Szunerits, Sabine; Boukherroub, Rabah; Giudici-Orticoni, Marie-Thérèse; Mano, Nicolas; Lojou, Elisabeth

    2016-09-01

    Due to the lack of a valid approach in the design of electrochemical interfaces modified with enzymes for efficient catalysis, many oxidoreductases are still not addressed by electrochemistry. We report in this work an in-depth study of the interactions between two different bilirubin oxidases, (from the fungus Myrothecium verrucaria and from the bacterium Bacillus pumilus), catalysts of oxygen reduction, and carbon nanotubes bearing various surface charges (pristine, carboxylic-, and pyrene-methylamine-functionalized). The surface charges and dipole moment of the enzymes as well as the surface state of the nanomaterials are characterized as a function of pH. An original electrochemical approach allows determination of the best interface for direct or mediated electron transfer processes as a function of enzyme, nanomaterial type, and adsorption conditions. We correlate these experimental results to theoric voltammetric curves. Such an integrative study suggests strategies for designing efficient bioelectrochemical interfaces toward the elaboration of biodevices such as enzymatic fuel cells for sustainable electricity production. PMID:27533778

  2. Study of Model Systems for Bilirubin and Bilin Chromophores: Determination and Modification of Thermal and Photochemical Properties.

    PubMed

    García-Iriepa, Cristina; Ernst, Hanna A; Liang, Yu; Unterreiner, Andreas-Neil; Frutos, Luis Manuel; Sampedro, Diego

    2016-08-01

    Bilin chromophores and bilirubin are involved in relevant biological functions such as light perception in plants and as protective agents against Alzheimer and other diseases. Despite their extensive use, a deep rationalization of the main factors controlling the thermal and photochemical properties has not been performed yet, which in turn hampers further applications of these versatile molecules. In an effort to understand those factors and allow control of the relevant properties, a combined experimental and computational study has been carried out for diverse model systems to understand the interconversion between Z and E isomers. In this study, we have demonstrated the crucial role of steric hindrance and hydrogen-bond interactions in thermal stability and the ability to control them by designing novel compounds. We also determined several photochemical properties and studied the photodynamics of two model systems in more detail, observing a fast relaxation of the excited state shorter than 2 ps in both cases. Finally, the computational study allowed us to rationalize the experimental evidence. PMID:27391671

  3. The effect of premature and delayed birth on the development of UDP-glucuronosyltransferase activities towards bilirubin, morphine and testosterone in the rat.

    PubMed Central

    Campbell, M T; Wishart, G J

    1980-01-01

    In the rat, UDP-glucuronosyltransferase activities towards bilirubin, morphine and testosterone increase markedly after normal or premature birth. This rapid development is superimposed upon a much slower maturation of activity which occurs in utero during the last 2 days of normal gestation and gestation when birth is delayed. Development of all three activities is similar under these different conditions, suggesting a common developmenpal regulatory mechanism. PMID:6769435

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

    PubMed Central

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

    1992-01-01

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

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

    SciTech Connect

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

    2014-07-18

    Highlights: • Proton transport pathway in bilirubin oxidase was mutated. • Two intermediates in the dioxygen reduction steps were trapped and characterized. • A specific glutamate for dioxygen reduction by multicopper oxidases was identified. - Abstract: The hydrogen bond network leading from bulk water to the trinuclear copper center in bilirubin oxidase is constructed with Glu463 and water molecules to transport protons for the four-electron reduction of dioxygen. Substitutions of Glu463 with Gln or Ala were attributed to virtually complete loss or significant reduction in enzymatic activities due to an inhibition of the proton transfer steps to dioxygen. The single turnover reaction of the Glu463Gln mutant afforded the highly magnetically interacted intermediate II (native intermediate) with a broad g = 1.96 electron paramagnetic resonance signal detectable at cryogenic temperatures. Reactions of the double mutants, Cys457Ser/Glu463Gln and Cys457Ser/Glu463Ala afforded the intermediate I (peroxide intermediate) because the type I copper center to donate the fourth electron to dioxygen was vacant in addition to the interference of proton transport due to the mutation at Glu463. The intermediate I gave no electron paramagnetic resonance signal, but the type II copper signal became detectable with the decay of the intermediate I. Structural and functional similarities between multicopper oxidases are discussed based on the present mutation at Glu463 in bilirubin oxidase.

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

    PubMed Central

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

    2010-01-01

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

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

    PubMed

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

    2014-03-01

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

  8. Influence of Phosphatidylcholine and Calcium on Self-Association and Bile Salt Mixed Micellar Binding of the Natural Bile Pigment, Bilirubin Ditaurate.

    PubMed

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

    2015-11-17

    Recently [Neubrand, M. W., et al. (2015) Biochemistry 54, 1542-1557], we determined a concentration-dependent monomer-dimer-tetramer equilibrium in aqueous bilirubin ditaurate (BDT) solutions and explored the nature of high-affinity binding of BDT monomers with monomers and micelles of the common taurine-conjugated bile salts (BS). We now investigate, employing complementary physicochemical methods, including fluorescence emission spectrophotometry and quasi-elastic light scattering spectroscopy, the influence of phosphatidylcholine (PC), the predominant phospholipid of bile and calcium, the major divalent biliary cation, on these self-interactions and heterointeractions. We have used short-chain, lyso and long-chain PC species as models and contrasted our results with those of parallel studies employing unconjugated bilirubin (UCB) as the fully charged dianion. Both bile pigments interacted with the zwitterionic headgroup of short-chain lecithins, forming water-soluble (BDT) and insoluble ion-pair complexes (UCB), respectively. Upon micelle formation, BDT monomers apparently remained at the headgroup mantle of short-chain PCs, but the ion pairs with UCB became internalized within the micelle's hydrophobic core. BDT interacted with the headgroups of unilamellar egg yolk (EY) PC vesicles; however, with the simultaneous addition of CaCl2, a reversible aggregation took place, but not vesicle fusion. With mixed EYPC/BS micelles, BDT became bound to the hydrophilic surface (as with simple BS micelles), and in turn, both BDT and BS bound calcium, but not other divalent cations. The calcium complexation of BDT and BS was enhanced strongly with increases in micellar EYPC, suggesting calcium-mediated cross-bridging of hydrophilic headgroups at the micelle's surface. Therefore, the physicochemical binding of BDT to BS in an artificial bile medium is influenced not only by BS species and concentration but also by long-chain PCs and calcium ions that exert a specific rather

  9. Bilirubin UDP-Glucuronosyltransferase 1A1 (UGT1A1) Gene Promoter Polymorphisms and HPRT, Glycophorin A, and Micronuclei Mutant Frequencies in Human Blood

    SciTech Connect

    Grant, D; Hall, I J; Eastmond, D; Jones, I M; Bell, D A

    2004-10-06

    A dinucleotide repeat polymorphism (5-, 6-, 7-, or 8-TA units) has been identified within the promoter region of UDP-glucuronosyltransferase 1A1 gene (UGT1A1). The 7-TA repeat allele has been associated with elevated serum bilirubin levels that cause a mild hyperbilirubinemia (Gilbert's syndrome). Studies suggest that promoter transcriptional activity of UGT1A1 is inversely related to the number of TA repeats and that unconjugated bilirubin concentration increases directly with the number of TA repeat elements. Because bilirubin is a known antioxidant, we hypothesized that UGT1A1 repeats associated with higher bilirubin may be protective against oxidative damage. We examined the effect of UGT1A1 genotype on somatic mutant frequency in the hypoxanthine-guanine phosphoribosyl-transferase (HPRT) gene in human lymphocytes and the glycophorin A (GPA) gene of red blood cells (both N0, NN mutants), and the frequency of lymphocyte micronuclei (both kinetochore (K) positive or micronuclei K negative) in 101 healthy smoking and nonsmoking individuals. As hypothesized, genotypes containing 7-TA and 8-TA displayed marginally lower GPA{_}NN mutant frequency relative to 5/5, 5/6, 6/6 genotypes (p<0.05). In contrast, our analysis showed that lower expressing UGT1A1 alleles (7-TA and 8-TA) were associated with modestly increased HPRT mutation frequency (p<0.05) while the same low expression genotypes were not significantly associated with micronuclei frequencies (K-positive or K-negative) when compared to high expression genotypes (5-TA and 6-TA). We found weak evidence that UGT1A1 genotypes containing 7-TA and 8-TA were associated with increased GPA{_}N0 mutant frequency relative to 5/5, 5/6, 6/6 genotypes (p<0.05). These data suggest that UGT1A1 genotype may modulate somatic mutation of some types, in some cell lineages, by a mechanism not involving bilirubin antioxidant activity. More detailed studies examining UGT1A1 promoter variation, oxidant/antioxidant balance and genetic

  10. Hydrophilic bile acids protect human blood-brain barrier endothelial cells from disruption by unconjugated bilirubin: an in vitro study

    PubMed Central

    Palmela, Inês; Correia, Leonor; Silva, Rui F. M.; Sasaki, Hiroyuki; Kim, Kwang S.; Brites, Dora; Brito, Maria A.

    2015-01-01

    Ursodeoxycholic acid and its main conjugate glycoursodeoxycholic acid are bile acids with neuroprotective properties. Our previous studies demonstrated their anti-apoptotic, anti-inflammatory, and antioxidant properties in neural cells exposed to elevated levels of unconjugated bilirubin (UCB) as in severe jaundice. In a simplified model of the blood-brain barrier, formed by confluent monolayers of a cell line of human brain microvascular endothelial cells, UCB has shown to induce caspase-3 activation and cell death, as well as interleukin-6 release and a loss of blood-brain barrier integrity. Here, we tested the preventive and restorative effects of these bile acids regarding the disruption of blood-brain barrier properties by UCB in in vitro conditions mimicking severe neonatal hyperbilirubinemia and using the same experimental blood-brain barrier model. Both bile acids reduced the apoptotic cell death induced by UCB, but only glycoursodeoxycholic acid significantly counteracted caspase-3 activation. Bile acids also prevented the upregulation of interleukin-6 mRNA, whereas only ursodeoxycholic acid abrogated cytokine release. Regarding barrier integrity, only ursodeoxycholic acid abrogated UCB-induced barrier permeability. Better protective effects were obtained by bile acid pre-treatment, but a strong efficacy was still observed by their addition after UCB treatment. Finally, both bile acids showed ability to cross confluent monolayers of human brain microvascular endothelial cells in a time-dependent manner. Collectively, data disclose a therapeutic time-window for preventive and restorative effects of ursodeoxycholic acid and glycoursodeoxycholic acid against UCB-induced blood-brain barrier disruption and damage to human brain microvascular endothelial cells. PMID:25821432

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

    PubMed Central

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

    2010-01-01

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

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

    PubMed

    Koníčková, Renata; Vaňková, Kateřina; Vaníková, Jana; Váňová, Kateřina; Muchová, Lucie; Subhanová, Iva; Zadinová, Marie; Zelenka, Jaroslav; Dvořák, Aleš; Kolář, Michal; Strnad, Hynek; Rimpelová, Silvie; Ruml, Tomáš; J Wong, Ronald; Vítek, Libor

    2014-01-01

    Spirulina platensis is a blue-green alga used as a dietary supplement because of its hypocholesterolemic properties. Among other bioactive substances, it is also rich in tetrapyrrolic compounds closely related to bilirubin molecule, a potent antioxidant and anti-proliferative agent. The aim of our study was to evaluate possible anticancer effects of S. platensis and S. platensis-derived tetrapyrroles using an experimental model of pancreatic cancer. The anti-proliferative effects of S. platensis and its tetrapyrrolic components [phycocyanobilin (PCB) and chlorophyllin, a surrogate molecule for chlorophyll A] were tested on several human pancreatic cancer cell lines and xenotransplanted nude mice. The effects of experimental therapeutics on mitochondrial reactive oxygen species (ROS) production and glutathione redox status were also evaluated. Compared to untreated cells, experimental therapeutics significantly decreased proliferation of human pancreatic cancer cell lines in vitro in a dose-dependent manner (from 0.16 g•L-1 [S. platensis], 60 μM [PCB], and 125 μM [chlorophyllin], p<0.05). The anti-proliferative effects of S. platensis were also shown in vivo, where inhibition of pancreatic cancer growth was evidenced since the third day of treatment (p < 0.05). All tested compounds decreased generation of mitochondrial ROS and glutathione redox status (p = 0.0006; 0.016; and 0.006 for S. platensis, PCB, and chlorophyllin, respectively). In conclusion, S. platensis and its tetrapyrrolic components substantially decreased the proliferation of experimental pancreatic cancer. These data support a chemopreventive role of this edible alga. Furthermore, it seems that dietary supplementation with this alga might enhance systemic pool of tetrapyrroles, known to be higher in subjects with Gilbert syndrome. PMID:24552870

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

    PubMed Central

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

    2014-01-01

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

  14. Rescue of bilirubin-induced neonatal lethality in a mouse model of Crigler-Najjar syndrome type I by AAV9-mediated gene transfer

    PubMed Central

    Bortolussi, Giulia; Zentilin, Lorena; Baj, Gabriele; Giraudi, Pablo; Bellarosa, Cristina; Giacca, Mauro; Tiribelli, Claudio; Muro, Andrés F.

    2012-01-01

    Crigler-Najjar type I (CNI) syndrome is a recessively inherited disorder characterized by severe unconjugated hyperbilirubinemia caused by uridine diphosphoglucuronosyltransferase 1A1 (UGT1A1) deficiency. The disease is lethal due to bilirubin-induced neurological damage unless phototherapy is applied from birth. However, treatment becomes less effective during growth, and liver transplantation is required. To investigate the pathophysiology of the disease and therapeutic approaches in mice, we generated a mouse model by introducing a premature stop codon in the UGT1a1 gene, which results in an inactive enzyme. Homozygous mutant mice developed severe jaundice soon after birth and died within 11 d, showing significant cerebellar alterations. To rescue neonatal lethality, newborns were injected with a single dose of adeno-associated viral vector 9 (AAV9) expressing the human UGT1A1. Gene therapy treatment completely rescued all AAV-treated mutant mice, accompanied by lower plasma bilirubin levels and normal brain histology and motor coordination. Our mouse model of CNI reproduces genetic and phenotypic features of the human disease. We have shown, for the first time, the full recovery of the lethal effects of neonatal hyperbilirubinemia. We believe that, besides gene-addition-based therapies, our mice could represent a very useful model to develop and test novel technologies based on gene correction by homologous recombination.—Bortolussi, G., Zentilin, L., Baj, G., Giraudi, P., Bellarosa, C., Giacca, M., Tiribelli, C., Muro, A. F. Rescue of bilirubin-induced neonatal lethality in a mouse model of Crigler-Najjar syndrome type I by AAV9-mediated gene transfer. PMID:22094718

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

    NASA Astrophysics Data System (ADS)

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

    2010-11-01

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

  16. Breast milk jaundice: in vitro inhibition of rat liver bilirubin-uridine diphosphate glucuronyltransferase activity and Z protein-bromosulfophthalein binding by human breast milk.

    PubMed

    Foliot, A; Ploussard, J P; Housset, E; Christoforov

    1976-06-01

    Twenty-four samples of breast milk from nine mothers of infants suffering from breast milk jaundice were studied. Eight samples of milk from mothers of nonjaundiced infants, along with five formula milks enriched with polyunsaturated fatty acids, served as controls. Milks from mothers with jaundiced infants had no inhibitory effect when assayed immediately after thawing. However, after these milk samples were stores at 4 degrees, they strongly inhibited bilirubin conjugation (80.3% inhibition of uridine diphosphate glucuronyltransferase (UDPGT) activity) and bromosulfophthalein (BSP) binding to cytoplasmic Z protein (dye binding inhibited 82.1%). There was no effect on BSP binding to Y protein (see Table 1). Heating the milk to 56 degrees modified the results in the following manner; when the milk was heated immediately after thawing, no inhibitory effect was seen, even after storage for 96 hr. On the other hand, when the milk was first stored at 96 hr and then heated, it had the same inhibitory effects as the milks which were stored without heating. The present study shows that pathologic breast milk will inhibit BSP-Z protein binding only when stored under conditions that also cause the appearance of the capacity to inhibit bilirubin conjugation in vitro, as well as causing the liberation of nonesterified fatty acids. Thus, the appearance of this inhibitory capacity in vitro seems linked to the lipolytic activity particular to pathologic milks. PMID:818610

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

    PubMed Central

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

    2015-01-01

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

  18. Modelling Aṣṭādhyāyī: An Approach Based on the Methodology of Ancillary Disciplines (Vedāṅga)

    NASA Astrophysics Data System (ADS)

    Mishra, Anand

    This article proposes a general model based on the common methodological approach of the ancillary disciplines (Vedāṅga) associated with the Vedas taking examples from Śikṣā, Chandas, Vyākaraṇa and Prātiśā khya texts. It develops and elaborates this model further to represent the contents and processes of Aṣṭādhyāyī. Certain key features are added to my earlier modelling of Pāṇinian system of Sanskrit grammar. This includes broader coverage of the Pāṇinian meta-language, mechanism for automatic application of rules and positioning the grammatical system within the procedural complexes of ancillary disciplines.

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

    PubMed

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

    2014-11-15

    Two types of carbon nanotube electrodes (1) buckypaper (BP) and (2) vertically aligned carbon nanotubes (vaCNT) have been used for elaboration of glucose/O2 enzymatic fuel cells exploiting direct electron transfer. For the anode pyrroloquinoline quinone dependent glucose dehydrogenase ((PQQ)GDH) has been immobilized on [poly(3-aminobenzoic acid-co-2-methoxyaniline-5-sulfonic acid), PABMSA]-modified electrodes. For the cathode bilirubin oxidase (BOD) has been immobilized on PQQ-modified electrodes. PABMSA and PQQ act as promoter for enzyme bioelectrocatalysis. The voltammetric characterization of each electrode shows current densities in the range of 0.7-1.3 mA/cm(2). The BP-based fuel cell exhibits maximal power density of about 107 µW/cm(2) (at 490 mV). The vaCNT-based fuel cell achieves a maximal power density of 122 µW/cm(2) (at 540 mV). Even after three days and several runs of load a power density over 110 µW/cm(2) is retained with the second system (10mM glucose). Due to a better power exhibition and an enhanced stability of the vaCNT-based fuel cells they have been studied in human serum samples and a maximal power density of 41 µW/cm(2) (390 mV) can be achieved. PMID:24967753

  20. Membraneless enzymatic ethanol/O2 fuel cell: Transitioning from an air-breathing Pt-based cathode to a bilirubin oxidase-based biocathode

    NASA Astrophysics Data System (ADS)

    Aquino Neto, Sidney; Milton, Ross D.; Hickey, David P.; De Andrade, Adalgisa R.; Minteer, Shelley D.

    2016-08-01

    The bioelectrooxidation of ethanol was investigated in a fully enzymatic membraneless ethanol/O2 biofuel cell assembly using hybrid bioanodes containing multi-walled carbon nanotube (MWCNT)-decorated gold metallic nanoparticles with either a pyrroloquinoline quinone (PQQ)-dependent alcohol dehydrogenase (ADH) enzyme or a nicotinamide adenine dinucleotide (NAD+)-dependent ADH enzyme. The biofuel cell anode was prepared with the PQQ-dependent enzyme and designed using either a direct electron transfer (DET) architecture or via a mediated electron transfer (MET) configuration through a redox polymer, 1,1‧-dimethylferrocene-modified linear polyethyleneimine (FcMe2-C3-LPEI). In the case of the bioanode containing the NAD+-dependent enzyme, only the mediated electron transfer mechanism was employed using an electropolymerized methylene green film to regenerate the NAD+ cofactor. Regardless of the enzyme being employed at the anode, a bilirubin oxidase-based biocathode prepared within a DET architecture afforded efficient electrocatalytic oxygen reduction in an ethanol/O2 biofuel cell. The power curves showed that DET-based bioanodes via the PQQ-dependent ADH still lack high current densities, whereas the MET architecture furnished maximum power density values as high as 226 ± 21 μW cm-2. Considering the complete membraneless enzymatic biofuel cell with the NAD+-dependent ADH-based bioanode, power densities as high as 111 ± 14 μW cm-2 were obtained. This shows the advantage of PQQ-dependent ADH for membraneless ethanol/O2 biofuel cell applications.

  1. Review: Bilirubin pKa studies; new models and theories indicate high pKa values in water, dimethylformamide and DMSO

    PubMed Central

    2010-01-01

    Background Correct aqueous pKa values of unconjugated bilirubin (UCB), a poorly-soluble, unstable substance, are essential for understanding its functions. Our prior solvent partition studies, of unlabeled and [14C] UCB, indicated pKa values above 8.0. These high values were attributed to effects of internal H-bonding in UCB. Many earlier and subsequent studies have reported lower pKa values, some even below 5.0, which are often used to describe the behavior of UCB. We here review 18 published studies that assessed aqueous pKa values of UCB, critically evaluating their methodologies in relation to essential preconditions for valid pKa measurements (short-duration experiments with purified UCB below saturation and accounting for self-association of UCB). Results These re-assessments identified major deficiencies that invalidate the results of all but our partition studies. New theoretical modeling of UCB titrations shows remarkable, unexpected effects of self-association, yielding falsely low pKa estimates, and provides some rationalization of the titration anomalies. The titration behavior reported for a soluble thioether conjugate of UCB at high aqueous concentrations is shown to be highly anomalous. Theoretical re-interpretations of data in DMSO and dimethylformamide show that those indirectly-derived aqueous pKa values are unacceptable, and indicate new, high average pKa values for UCB in non-aqueous media (>11 in DMSO and, probably, >10 in dimethylformamide). Conclusions No reliable aqueous pKa values of UCB are available for comparison with our partition-derived results. A companion paper shows that only the high pKa values can explain the pH-dependence of UCB binding to phospholipids, cyclodextrins, and alkyl-glycoside and bile salt micelles. PMID:20350304

  2. Metastable and equilibrium phase diagrams of unconjugated bilirubin IXα as functions of pH in model bile systems: Implications for pigment gallstone formation

    PubMed Central

    Berman, Marvin D.

    2014-01-01

    Metastable and equilibrium phase diagrams for unconjugated bilirubin IXα (UCB) in bile are yet to be determined for understanding the physical chemistry of pigment gallstone formation. Also, UCB is a molecule of considerable biomedical importance because it is a potent antioxidant and an inhibitor of atherogenesis. We employed principally a titrimetric approach to obtain metastable and equilibrium UCB solubilities in model bile systems composed of taurine-conjugated bile salts, egg yolk lecithin (mixed long-chain phosphatidylcholines), and cholesterol as functions of total lipid concentration, biliary pH values, and CaCl2 plus NaCl concentrations. Metastable and equilibrium precipitation pH values were obtained, and average pKa values of the two carboxyl groups of UCB were calculated. Added lecithin and increased temperature decreased UCB solubility markedly, whereas increases in bile salt concentrations and molar levels of urea augmented solubility. A wide range of NaCl and cholesterol concentrations resulted in no specific effects, whereas added CaCl2 produced large decreases in UCB solubilities at alkaline pH values only. UV-visible absorption spectra were consistent with both hydrophobic and hydrophilic interactions between UCB and bile salts that were strongly influenced by pH. Reliable literature values for UCB compositions of native gallbladder biles revealed that biles from hemolytic mice and humans with black pigment gallstones are markedly supersaturated with UCB and exhibit more acidic pH values, whereas biles from nonstone control animals and patients with cholesterol gallstone are unsaturated with UCB. PMID:25359538

  3. Metastable and equilibrium phase diagrams of unconjugated bilirubin IXα as functions of pH in model bile systems: Implications for pigment gallstone formation.

    PubMed

    Berman, Marvin D; Carey, Martin C

    2015-01-01

    Metastable and equilibrium phase diagrams for unconjugated bilirubin IXα (UCB) in bile are yet to be determined for understanding the physical chemistry of pigment gallstone formation. Also, UCB is a molecule of considerable biomedical importance because it is a potent antioxidant and an inhibitor of atherogenesis. We employed principally a titrimetric approach to obtain metastable and equilibrium UCB solubilities in model bile systems composed of taurine-conjugated bile salts, egg yolk lecithin (mixed long-chain phosphatidylcholines), and cholesterol as functions of total lipid concentration, biliary pH values, and CaCl2 plus NaCl concentrations. Metastable and equilibrium precipitation pH values were obtained, and average pKa values of the two carboxyl groups of UCB were calculated. Added lecithin and increased temperature decreased UCB solubility markedly, whereas increases in bile salt concentrations and molar levels of urea augmented solubility. A wide range of NaCl and cholesterol concentrations resulted in no specific effects, whereas added CaCl2 produced large decreases in UCB solubilities at alkaline pH values only. UV-visible absorption spectra were consistent with both hydrophobic and hydrophilic interactions between UCB and bile salts that were strongly influenced by pH. Reliable literature values for UCB compositions of native gallbladder biles revealed that biles from hemolytic mice and humans with black pigment gallstones are markedly supersaturated with UCB and exhibit more acidic pH values, whereas biles from nonstone control animals and patients with cholesterol gallstone are unsaturated with UCB. PMID:25359538

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

    PubMed

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

    2016-09-01

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

  5. Membraneless enzymatic ethanol/O2 fuel cell: Transitioning from an air-breathing Pt-based cathode to a bilirubin oxidase-based biocathode

    NASA Astrophysics Data System (ADS)

    Aquino Neto, Sidney; Milton, Ross D.; Hickey, David P.; De Andrade, Adalgisa R.; Minteer, Shelley D.

    2016-08-01

    The bioelectrooxidation of ethanol was investigated in a fully enzymatic membraneless ethanol/O2 biofuel cell assembly using hybrid bioanodes containing multi-walled carbon nanotube (MWCNT)-decorated gold metallic nanoparticles with either a pyrroloquinoline quinone (PQQ)-dependent alcohol dehydrogenase (ADH) enzyme or a nicotinamide adenine dinucleotide (NAD+)-dependent ADH enzyme. The biofuel cell anode was prepared with the PQQ-dependent enzyme and designed using either a direct electron transfer (DET) architecture or via a mediated electron transfer (MET) configuration through a redox polymer, 1,1‧-dimethylferrocene-modified linear polyethyleneimine (FcMe2-C3-LPEI). In the case of the bioanode containing the NAD+-dependent enzyme, only the mediated electron transfer mechanism was employed using an electropolymerized methylene green film to regenerate the NAD+ cofactor. Regardless of the enzyme being employed at the anode, a bilirubin oxidase-based biocathode prepared within a DET architecture afforded efficient electrocatalytic oxygen reduction in an ethanol/O2 biofuel cell. The power curves showed that DET-based bioanodes via the PQQ-dependent ADH still lack high current densities, whereas the MET architecture furnished maximum power density values as high as 226 ± 21 μW cm-2. Considering the complete membraneless enzymatic biofuel cell with the NAD+-dependent ADH-based bioanode, power densities as high as 111 ± 14 μW cm-2 were obtained. This shows the advantage of PQQ-dependent ADH for membraneless ethanol/O2 biofuel cell applications.

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

    PubMed Central

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

    2015-01-01

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

  7. Endothelial Cells Derived from the Blood-Brain Barrier and Islets of Langerhans Differ in their Response to the Effects of Bilirubin on Oxidative Stress Under Hyperglycemic Conditions.

    PubMed

    Kapitulnik, Jaime; Benaim, Clara; Sasson, Shlomo

    2012-01-01

    Unconjugated bilirubin (UCB) is a neurotoxic degradation product of heme. Its toxic effects include induction of apoptosis, and ultimately neuronal cell death. However, at low concentrations, UCB is a potent antioxidant that may protect cells and tissues against oxidative stress by neutralizing toxic metabolites such as reactive oxygen species (ROS). High glucose levels (hyperglycemia) generate reactive metabolites. Endothelial cell dysfunction, an early vascular complication in diabetes, has been associated with hyperglycemia-induced oxidative stress. Both glucose and UCB are substrates for transport proteins in microvascular endothelial cells of the blood-brain barrier (BBB). In the current study we show that UCB (1-40 μM) induces apoptosis and reduces survival of bEnd3 cells, a mouse brain endothelial cell line which serves as an in vitro model of the BBB. These deleterious effects of UCB were enhanced in the presence of high glucose (25 mM) levels. Interestingly, the bEnd3 cells exhibited an increased sensitivity to the apoptotic effects of UCB when compared to the MS1 microcapillary endothelial cell line. MS1 cells originate from murine pancreatic islets of Langerhans, and are devoid of the barrier characteristics of BBB-derived endothelial cells. ROS production was increased in both bEnd3 and MS1 cells exposed to high glucose, as compared with cells exposed to normal (5.5 mM) glucose levels. While UCB (0.1-40 μM) did not alter ROS production in cells exposed to normal glucose, relatively low ("physiological") UCB concentrations (0.1-5 μM) attenuated ROS generation in both cell lines exposed to high glucose levels. Most strikingly, higher UCB concentrations (20-40 μM) increased ROS generation in bEnd3 cells exposed to high glucose, but not in similarly treated MS1 cells. These results may be of critical importance for understanding the vulnerability of the BBB endothelium upon exposure to increasing UCB levels under hyperglycemic conditions

  8. Endothelial Cells Derived from the Blood-Brain Barrier and Islets of Langerhans Differ in their Response to the Effects of Bilirubin on Oxidative Stress Under Hyperglycemic Conditions

    PubMed Central

    Kapitulnik, Jaime; Benaim, Clara; Sasson, Shlomo

    2012-01-01

    Unconjugated bilirubin (UCB) is a neurotoxic degradation product of heme. Its toxic effects include induction of apoptosis, and ultimately neuronal cell death. However, at low concentrations, UCB is a potent antioxidant that may protect cells and tissues against oxidative stress by neutralizing toxic metabolites such as reactive oxygen species (ROS). High glucose levels (hyperglycemia) generate reactive metabolites. Endothelial cell dysfunction, an early vascular complication in diabetes, has been associated with hyperglycemia-induced oxidative stress. Both glucose and UCB are substrates for transport proteins in microvascular endothelial cells of the blood-brain barrier (BBB). In the current study we show that UCB (1–40 μM) induces apoptosis and reduces survival of bEnd3 cells, a mouse brain endothelial cell line which serves as an in vitro model of the BBB. These deleterious effects of UCB were enhanced in the presence of high glucose (25 mM) levels. Interestingly, the bEnd3 cells exhibited an increased sensitivity to the apoptotic effects of UCB when compared to the MS1 microcapillary endothelial cell line. MS1 cells originate from murine pancreatic islets of Langerhans, and are devoid of the barrier characteristics of BBB-derived endothelial cells. ROS production was increased in both bEnd3 and MS1 cells exposed to high glucose, as compared with cells exposed to normal (5.5 mM) glucose levels. While UCB (0.1–40 μM) did not alter ROS production in cells exposed to normal glucose, relatively low (“physiological”) UCB concentrations (0.1–5 μM) attenuated ROS generation in both cell lines exposed to high glucose levels. Most strikingly, higher UCB concentrations (20–40 μM) increased ROS generation in bEnd3 cells exposed to high glucose, but not in similarly treated MS1 cells. These results may be of critical importance for understanding the vulnerability of the BBB endothelium upon exposure to increasing UCB levels under hyperglycemic

  9. Unconjugated bilirubin elevation impairs the function and expression of breast cancer resistance protein (BCRP) at the blood-brain barrier in bile duct-ligated rats

    PubMed Central

    Xu, Ping; Ling, Zhao-li; Zhang, Ji; Li, Ying; Shu, Nan; Zhong, Ze-yu; Chen, Yang; Di, Xin-yu; Wang, Zhong-jian; Liu, Li; Liu, Xiao-dong

    2016-01-01

    Aim: Liver failure is associated with dyshomeostasis of efflux transporters at the blood-brain barrier (BBB), which contributes to hepatic encephalopathy. In this study we examined whether breast cancer resistance protein (BCRP), a major efflux transporter at the BBB, was altered during liver failure in rats. Methods: Rats underwent bile duct ligation (BDL) surgery, and then were sacrificed after intravenous injection of prazosin on d3, d7 and d14. The brains and blood samples were collected. BCRP function at the BBB was assessed by the brain-to-plasma prazosin concentration ratio; Evans Blue extravasation in the brain tissues was used as an indicator of BBB integrity. The protein levels of BCRP in the brain tissues were detected. Human cerebral microvessel endothelial cells (HCMEC/D3) and Madin-Darby canine kidney cells expressing human BCRP (MDCK-BCRP) were tested in vitro. In addition, hyperbilirubinemia (HB) was induced in rats by intravenous injection of unconjugated bilirubin (UCB). Results: BDL rats exhibited progressive decline of liver function and HB from d3 to d14. In the brain tissues of BDL rats, both the function and protein levels of BCRP were progressively decreased, whereas the BBB integrity was intact. Furthermore, BDL rat serum significantly decreased BCRP function and protein levels in HCMEC/D3 cells. Among the abnormally altered components in BDL rat serum tested, UCB (10, 25 μmol/L) dose-dependently inhibit BCRP function and protein levels in HCMEC/D3 cells, whereas 3 bile acids (CDCA, UDCA and DCA) had no effect. Similar results were obtained in MDCK-BCRP cells and in the brains of HB rats. Correlation analysis revealed that UCB levels were negatively correlated with BCRP expression in the brain tissues of BDL rats and HB rats as well as in two types of cells tested in vitro. Conclusion: UCB elevation in BDL rats impairs the function and expression of BCRP at the BBB, thus contributing to hepatic encephalopathy. PMID:27180978

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

    PubMed

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

    2015-02-24

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

  11. Conjugated Bilirubin Differentially Regulates CD4+ T Effector Cells and T Regulatory Cell Function through Outside-In and Inside-Out Mechanisms: The Effects of HAV Cell Surface Receptor and Intracellular Signaling.

    PubMed

    Corral-Jara, Karla F; Trujillo-Ochoa, Jorge L; Realpe, Mauricio; Panduro, Arturo; Gómez-Leyva, Juan F; Rosenstein, Yvonne; Jose-Abrego, Alexis; Roman, Sonia; Fierro, Nora A

    2016-01-01

    We recently reported an immune-modulatory role of conjugated bilirubin (CB) in hepatitis A virus (HAV) infection. During this infection the immune response relies on CD4+ T lymphocytes (TLs) and it may be affected by the interaction of HAV with its cellular receptor (HAVCR1/TIM-1) on T cell surface. How CB might affect T cell function during HAV infection remains to be elucidated. Herein, in vitro stimulation of CD4+ TLs from healthy donors with CB resulted in a decrease in the degree of intracellular tyrosine phosphorylation and an increase in the activity of T regulatory cells (Tregs) expressing HAVCR1/TIM-1. A comparison between CD4+ TLs from healthy donors and HAV-infected patients revealed changes in the TCR signaling pathway relative to changes in CB levels. The proportion of CD4+CD25+ TLs increased in patients with low CB serum levels and an increase in the percentage of Tregs expressing HAVCR1/TIM-1 was found in HAV-infected patients relative to controls. A low frequency of 157insMTTTVP insertion in the viral receptor gene HAVCR1/TIM-1 was found in patients and controls. Our data revealed that, during HAV infection, CB differentially regulates CD4+ TLs and Tregs functions by modulating intracellular pathways and by inducing changes in the proportion of Tregs expressing HAVCR1/TIM-1. PMID:27578921

  12. Conjugated Bilirubin Differentially Regulates CD4+ T Effector Cells and T Regulatory Cell Function through Outside-In and Inside-Out Mechanisms: The Effects of HAV Cell Surface Receptor and Intracellular Signaling

    PubMed Central

    Corral-Jara, Karla F.; Gómez-Leyva, Juan F.; Rosenstein, Yvonne; Jose-Abrego, Alexis; Roman, Sonia

    2016-01-01

    We recently reported an immune-modulatory role of conjugated bilirubin (CB) in hepatitis A virus (HAV) infection. During this infection the immune response relies on CD4+ T lymphocytes (TLs) and it may be affected by the interaction of HAV with its cellular receptor (HAVCR1/TIM-1) on T cell surface. How CB might affect T cell function during HAV infection remains to be elucidated. Herein, in vitro stimulation of CD4+ TLs from healthy donors with CB resulted in a decrease in the degree of intracellular tyrosine phosphorylation and an increase in the activity of T regulatory cells (Tregs) expressing HAVCR1/TIM-1. A comparison between CD4+ TLs from healthy donors and HAV-infected patients revealed changes in the TCR signaling pathway relative to changes in CB levels. The proportion of CD4+CD25+ TLs increased in patients with low CB serum levels and an increase in the percentage of Tregs expressing HAVCR1/TIM-1 was found in HAV-infected patients relative to controls. A low frequency of 157insMTTTVP insertion in the viral receptor gene HAVCR1/TIM-1 was found in patients and controls. Our data revealed that, during HAV infection, CB differentially regulates CD4+ TLs and Tregs functions by modulating intracellular pathways and by inducing changes in the proportion of Tregs expressing HAVCR1/TIM-1. PMID:27578921

  13. Comparison of Serum Uric Acid, Bilirubin, and C-Reactive Protein as Prognostic Biomarkers of In-Hospital MACE Between Women and Men With ST-Segment Elevation Myocardial Infarction.

    PubMed

    Baumann, Stefan; Huseynov, Aydin; Koepp, Johanna; Jabbour, Claude; Behnes, Michael; Becher, Tobias; Renker, Matthias; Lang, Siegfried; Borggrefe, Martin; Lehmann, Ralf; Akin, Ibrahim

    2016-03-01

    Levels of C-reactive protein (CRP), uric acid (UA), and total bilirubin (TB) are associated with coronary artery disease and major adverse cardiac events (MACEs) in patients with ST-segment elevation myocardial infarction (STEMI). We retrospectively included 1167 patients with STEMI who underwent percutaneous coronary intervention and routine blood sampling. The study cohort consisted of 803 patients (73.1% male, mean age 62.5 ± 13.4 years). In men, the levels of CRP, TB, and UA were significantly higher in the MACE than in the non-MACE group (P < .05). The receiver-operating characteristic (ROC) analysis shows that CRP (area under the curve [AUC]: 0.59; 95% confidence interval [CI]: 0.53-0.66; P = .014) and TB (AUC: 0.58; 95% CI: 0.51-0.65; P = .019) are significantly associated with MACE but not UA (AUC: 0.61; 95% CI: 0.42-0.76; P = .083). Logistic regression revealed CRP (odds ratio [OR] 1.01; 95% CI: 1.00-1.01; P = .006) and TB (OR 2.03; 95% CI: 1.12-3.40; P = .007) as an independent predictor for MACE. In women, none of the biomarkers was associated with MACE by ROC analysis or logistic regression analysis. This study demonstrated that high CRP and TB serum levels have a prognostic association with in-hospital MACE in male patients with STEMI. PMID:26032849

  14. [Maltodextrin in a 13% solution as a supplement in the first 4 days of life in breast-fed mature newborn infants. Effect on drinking behavior, weight curve, blood picture, blood glucose and bilirubin].

    PubMed

    Rosegger, H

    1986-05-16

    200 mature healthy newborn infants (birthweight 3382 +/- 377 g) were randomly divided into 2 groups of 100 each: all were breast fed according to the guidelines recommended by 'La Leche League'. If possible breast feeding was commenced in the delivery room. When breast feeds did not suffice infants of group A were supplemented ad libitum with a fully adapted formula (67 kcal/dl), those of group B with a 13% maltodextrine solution (52 kcal, 160 mOsm/l). Total fluid intake was similar in both groups. Group A took less supplementary feeds on day 2, the caloric uptake, however, was not different from that of group B. On day 4 group A had a somewhat higher caloric uptake due to supplementation, whereas group B needed less supplementation but had a higher intake of breast milk. On day 5 all babies were entirely breast fed. No supplementation was handed over to the mothers for at home use. The frequency of breast meals and supplementary meals was almost equal for both groups, as were sucking activity, appetite and degree of saturation. 18.6% of the infants in both groups had no need for any supplementary feeding at all. Temperature, stools, weight loss, blood glucose and bilirubin (taken on day 4 simultaneously with the Guthrie test) were almost identical. The red blood cell count showed slightly higher values in group A. Supplementation with fully adapted formula was not advantageous over supplementation with 13% maltodextrine solution. The latter was, indeed, tolerated well in all cases and satisfied all infants who remained hungry after being breast fed; additional early exposure to cow-milk protein was, thus, avoided in all these cases. PMID:3727591

  15. Early steps in bilirubin-mediated apoptosis in murine hepatoma (Hepa 1c1c7) cells are characterized by aryl hydrocarbon receptor-independent oxidative stress and activation of the mitochondrial pathway.

    PubMed

    Oakes, Garth H; Bend, John R

    2005-01-01

    Unconjugated bilirubin (UCB), the end product of heme catabolism, causes apoptosis in cells of the central nervous system, endothelial cells, and hepatotoma cells. However, the molecular mechanisms that contribute to UCB cytotoxicity remain unclear. The purpose of this study was to characterize the sequence of early events leading to UCB-mediated cytotoxicity in murine hepatoma Hepa 1c1c7 cells. In the present study, UCB (5-50 microM) was found to markedly increase the intracellular generation of reactive oxygen species (ROS) in a concentration-dependent manner, which is significantly elevated by 30 min post-treatment. This generation of ROS by UCB is not dependent on aryl hydrocarbon receptor (Ahr) signaling, as cells deficient in the Ahr (C12 cells) or the Ahr nuclear translocator protein (Arnt; C4 cells) were as efficient at generating ROS as wild type (WT) Hepa 1c1c7 cells. Mitochondrial membrane depolarization, evaluated with the lipophilic cationic dye, JC-1, occurred at least by 2 h after treatment with 50 muM UCB. Analysis of the caspase cascade demonstrated that activation of caspase-9 preceded activation of caspase-3. No conversion of procaspase-2 to active caspase-2 was detected in this study. These results demonstrate that UCB-mediated apoptosis in Hepa 1c1c7 cells is associated with increased oxidative stress and that caspase-9, and definitely not caspase-2, is the initiator caspase for apoptosis in UCB-treated Hepa 1c1c7 cells. PMID:16173058

  16. Acute, severe bilirubin encephalopathy in a newborn.

    PubMed

    Mollen, Thomas J; Scarfone, Richard; Harris, Mary Catherine

    2004-09-01

    In recent years, changes in health care practices including the early discharge of newborns have transformed the management of neonatal jaundice into an outpatient problem. At the same time, there has been a resurgence in the incidence of kernicterus. We report the case of a term male infant who presented to our emergency department at 4 days of age with severe jaundice and who subsequently died with autopsy findings of kernicterus. We review the infant's presentation and hospital course, diagnostic and therapeutic interventions, and autopsy findings. In the current era of increased frequency of breast-feeding, shortened hospital stays, and inconsistent follow-up after hospital discharge, emergency department physicians should be alerted to the rare but increasing occurrence of severe hyperbilirubinemia and kernicterus. PMID:15599261

  17. Determining Prevalence of Acute Bilirubin Encephalopathy in Developing Countries

    ClinicalTrials.gov

    2015-11-11

    Demonstrate BIND II Score of >=5, is Valid for Detecting Moderate to Severe ABE in Neonates <14 Days Old.; Demonstrate Community-BIND Instrument, a Modified BIND II, is a Valid and Reliable Tool for Detecting ABE.; Demonstrate That Community-BIND Can be Used for Acquiring Population-based Prevalence of ABE in the Community.

  18. Changes of blood plasma optical absorption spectrum due to bilirubin photoconversion

    NASA Astrophysics Data System (ADS)

    Altshuler, V. M.; Khanin, Yakov I.; Mironov, Yury A.

    1993-06-01

    This paper discusses some of our experimental results on the organism immunity increase caused by an intravenous UV irradiation of blood. The rabbits from an experimental group were treated with an optical fiber (620 micrometers core diameter) introduced to vena auricularis superficialis lateralis of the rabbits' ear. Pulsed UV laser emission was introduced through the optical fiber and rabbits' blood was irradiated for 10 minutes with the pulse repetition rate of 10 Hz. Subsequently, all rabbits from the experimental and a reference group were infected with the virulent strain of Staphylococcus aureus H 470. These results clearly indicate that the intravenous UV laser irradiation of blood had a positive therapeutic effect on the course of the animals' staphylococcal infection.

  19. Crigler-Najjar syndrome

    MedlinePlus

    ... biopsy Total bilirubin level Unconjugated (unbound) bilirubin in blood ... this is done using bilirubin lights (bili or 'blue' lights). ... Blood transfusions may help control the amount of bilirubin ...

  20. Transient response of a vertical electric dipole (VED) on a two-layer medium

    NASA Astrophysics Data System (ADS)

    Poh, S. Y.; Kong, J. A.

    The transient electromagnetic radiation by a vertical electric dipole on a two-layer medium is analyzed using the double deformation technique, which is a modal technique based on identification of singularities in the complex frequency and wavenumber planes. Previous application of the double deformation technique to the solution of this problem is incomplete in the early time response. In this paper it is shown that the existence of a pole locus on the negative imaginary frequency axis, which dominates the early time response, proves crucial in obtaining the solution for all times. A variety of combinations of parameters are used to illustrate the double deformation technique, and results will be compared with those obtained via explicit inversion, and a single deformation method.

  1. A Comparison of Community College Responders and Nonresponders to the VEDS Student Follow-Up Survey.

    ERIC Educational Resources Information Center

    Carifio, James; And Others

    1991-01-01

    A survey of respondents and nonrespondents to the Vocational Education Data System's follow-up survey of Massachusetts community college graduates was designed to measure response bias. The survey investigated employment patterns, wages, and degree of job relatedness. Results suggest original data was biased, if at all, toward underestimation, not…

  2. Interplay of co-inherited diseases can turn benign syndromes in a deadly combination: haemoglobinopathy and bilirubin transport disorder.

    PubMed

    Stolmeijer, T M; van der Berg, A P; Koeze, J; Gouw, A S H; Croles, F N; Sieders, E; Zijlstra, J G

    2015-06-01

    We present a case about a 25-year-old male patient suffering from a rare genetic disorder called Mizuho haemoglobin. He was admitted to the Intensive Care Unit with acute liver and renal failure. During admission he also developed a cardiac tamponade twice. Finally he received a liver transplantation. Hereafter the patient stabilised and his liver and renal functions improved. His symptoms could not be explained solely by his known disease. After searching the literature, similarities between his symptoms and a rare complication of sickle cell disease were found. Molecular diagnostics showed that the patient also suffered from Gilbert's syndrome. Due to his chronic haemolysis, symptoms of this other disease were masked. This stresses the importance of always looking for other causes if symptoms or changes cannot be explained by a known rare disorder. PMID:26087805

  3. Tumour suppressor protein p53 regulates the stress activated bilirubin oxidase cytochrome P450 2A6.

    PubMed

    Hu, Hao; Yu, Ting; Arpiainen, Satu; Lang, Matti A; Hakkola, Jukka; Abu-Bakar, A'edah

    2015-11-15

    Human cytochrome P450 (CYP) 2A6 enzyme has been proposed to play a role in cellular defence against chemical-induced oxidative stress. The encoding gene is regulated by various stress activated transcription factors. This paper demonstrates that p53 is a novel transcriptional regulator of the gene. Sequence analysis of the CYP2A6 promoter revealed six putative p53 binding sites in a 3kb proximate promoter region. The site closest to transcription start site (TSS) is highly homologous with the p53 consensus sequence. Transfection with various stepwise deletions of CYP2A6-5'-Luc constructs--down to -160bp from the TSS--showed p53 responsiveness in p53 overexpressed C3A cells. However, a further deletion from -160 to -74bp, including the putative p53 binding site, totally abolished the p53 responsiveness. Electrophoretic mobility shift assay with a probe containing the putative binding site showed specific binding of p53. A point mutation at the binding site abolished both the binding and responsiveness of the recombinant gene to p53. Up-regulation of the endogenous p53 with benzo[α]pyrene--a well-known p53 activator--increased the expression of the p53 responsive positive control and the CYP2A6-5'-Luc construct containing the intact p53 binding site but not the mutated CYP2A6-5'-Luc construct. Finally, inducibility of the native CYP2A6 gene by benzo[α]pyrene was demonstrated by dose-dependent increases in CYP2A6 mRNA and protein levels along with increased p53 levels in the nucleus. Collectively, the results indicate that p53 protein is a regulator of the CYP2A6 gene in C3A cells and further support the putative cytoprotective role of CYP2A6. PMID:26343999

  4. ABC-VED Analysis of a Drug Store in the Department of Community Medicine of a Medical College in Delhi.

    PubMed

    Anand, T; Ingle, G K; Kishore, J; Kumar, R

    2013-01-01

    A matrix based on coupling of cost (always, better and control) analysis and criticality (vital, essential and desirable) analysis was employed for drug inventory containing 129 items of drug store in the Department of Community Medicine of a Medical College in Delhi. The annual drug expenditure incurred on 129 drug items for the year 2010-2011 was found to be Rs. 4,35,847.85. On always, better and control analysis, 18.6, 24.0 and 57.4% drugs were found to be always, better and control category items, respectively, amounting for 69.1, 20.8 and 10.1% of annual drug expenditure. About 13.2 (17), 38.8 (50) and 48.0% (62) items were found to be vital, essential and desirable category items, respectively, amounting for 18.7, 49.5 and 31.8% of annual drug expenditure. Based on always, better and control-vital, essential and desirable matrix analysis there were 37 (28.68%) items in category I, 53 (41.09%) items in category II and 39 (30.23%) items in category III, amounting for 73.0, 22.2 and 4.8% of annual drug expenditure, respectively. To conclude, scientific inventory management tools are needed to be applied in routine for efficient management of the pharmacy stores as it contributes to not only in improvement in patient care but also judicious use of resources as well. PMID:23901172

  5. [Diabetes and alternative medicine: diabetic patients experiences with Ayur-Ved, "clinical ecology" and "cellular nutrition" methods].

    PubMed

    Vanelli, M; Chiari, G; Gugliotta, M; Capuano, C; Giacalone, T; Gruppi, L; Condò, M

    2002-04-01

    In the last two years we discovered that three of our patients with type 1 diabetes mellitus (0.8%) suffered an unexpected worsening in their glycemic control due to a reduction of their insulin dosage in favour of some "alternative" diabetes treatments using herbs, vitamins, fantastic diets and trace elements prescribed by non-medical practitioners. The first patient, a 6.6 year old boy, was admitted to hospital because of a severe ketoacidosis with first degree coma as a result of his parents having reduced his insulin dosage by 77% and replacing the insulin with an ayurvedic herbal preparation (Bardana Actium Lapp). The second patient, a 10.4 year old boy, was admitted to hospital after his teachers noticed that he appeared tired, thinner and polyuric. During hospital admission for mild ketoacidosis the mother, reluctant at first, finally confessed that her son was under the care of a "clinical ecologist". Having identified several food allergies this "clinical ecologist" had placed the child on a spartan diet of bread, water and salt, and had reduced his insulin dosage by 68%. The third patient, a 21 year old male, upon transfer to the Adult Diabetic Center, reported that he had been under the care of a pranotherapist for several years. The pranotherapist had prescribed a cellular nutrition preparation (called "Madonna drops"), a meditation program and also a 50% reduction in his insulin dosage. During this period his HbAlc values had increased from 6.4% to 12%. Current orthodox diabetes treatments are considered unsatisfactory by many people and it is thus not surprising that they search for "miracle" cures. It is important, however, that hospital staff do not ridicule the patients or their parents for trying these alternative therapies. Nevertheless, it would be useful for staff to discuss in advance these "therapies" with patients, highlighting their ineffectiveness and strongly discouraging cures that call for a reduction or elimination of the insulin treatment. PMID:11981532

  6. Cloning and stable expression of a new member of the human liver phenol/bilirubin: UDP-glucuronosyltransferase cDNA family.

    PubMed Central

    Wooster, R; Sutherland, L; Ebner, T; Clarke, D; Da Cruz e Silva, O; Burchell, B

    1991-01-01

    A new human liver UDP-glucuronosyltransferase (HlugP4) has been cloned and expressed in cell culture. The expressed enzyme has a molecular mass of 56 kDa and preferentially catalysed the glucuronidation of halogenated and bulky alkyl phenols. The C-terminal half of the sequence (246 amino acids) is 96% identical with the same portion of HlugP1, whereas the N-terminal half of the deduced protein sequences are only 38% identical. These results suggest that the two isoenzymes may be derived from the same gene by differential splicing of the gene product. Images Fig. 2. PMID:1910331

  7. Bili lights

    MedlinePlus

    Phototherapy for jaundice; Bilirubin - bili lights; Neonatal care - bili lights; Newborn care - bili lights ... Phototherapy involves shining fluorescent light from the bili lights on bare skin. A specific wavelength of light can break down bilirubin into a form that ...

  8. Blood Test: Comprehensive Metabolic Panel (CMP)

    MedlinePlus

    ... may signal a decrease in kidney function. Alkaline phosphatase (ALP) , alanine amino transferase (ALT) , aspartate amino transferase (AST) , and bilirubin ; ALP, ALT, and AST are liver enzymes; bilirubin is produced by the liver. Elevated concentrations ...

  9. Bile duct obstruction

    MedlinePlus

    ... the liver. It contains cholesterol, bile salts, and waste products such as bilirubin . Bile salts help your ... can lead to life-threatening infection and a dangerous buildup of bilirubin. If the blockage lasts a ...

  10. How Is Rh Incompatibility Treated?

    MedlinePlus

    ... of the skin and whites of the eyes). High levels of bilirubin cause jaundice. Reducing the blood's bilirubin level is important because high levels of this compound can cause brain damage. High ...

  11. Penile rehabilitation with a vacuum erectile device in an animal model is related to an antihypoxic mechanism: blood gas evidence.

    PubMed

    Lin, Hao-Cheng; Yang, Wen-Li; Zhang, Jun-Lan; Dai, Yu-Tian; Wang, Run

    2013-05-01

    Our previous study showed that vacuum erectile device (VED) therapy has improved erectile function in rats with bilateral cavernous nerve crush (BCNC) injuries. This study was designed to explore the mechanism of VED in penile rehabilitation by analyzing cavernous oxygen saturation (SO2) and to examine the effect of VED therapy on preventing penile shrinkage after BCNC. Thirty adult Sprague-Dawley rats were randomly assigned into three groups: group 1, sham surgery; group 2, BCNC; and group 3, BCNC+VED. Penile length and diameter were measured on a weekly basis. After 4 weeks of therapy, the penile blood was extracted by three methods for blood gas analysis (BGA): method 1, cavernous blood was aspirated at the flaccid state; method 2, cavernous blood was aspirated at the traction state; and method 3, cavernous blood was aspirated immediately after applying VED. SO2 values were tested by the blood gas analyzer. The results showed that VED therapy is effective in preventing penile shrinkage induced by BCNC (Penile shortening: BCNC group 1.9±1.1 mm; VED group 0.3±1.0 mm; P<0.01. Penile diameter reduction: BCNC group 0.28±0.14 mm; VED group 0.04±0.14 mm; P<0.01). The mean SO2±s.d. values were increased by VED application (88.25%±4.94%) compared to the flaccid (76.53%±4.16%) or traction groups (78.93%±2.56%) (P<0.05). The calculated blood constructs in the corpus cavernosum right after VED application were 62% arterial and 38% venous blood. These findings suggest that VED therapy can effectively preserve penile size in rats with BCNC injury. The beneficial effect of VED therapy is related to antihypoxia by increasing cavernous blood SO2. PMID:23564044

  12. Hyperbilirubinemia in Preterm Neonates.

    PubMed

    Bhutani, Vinod K; Wong, Ronald J; Stevenson, David K

    2016-06-01

    Preterm neonates with increased bilirubin production loads are more likely to sustain adverse outcomes due to either neurotoxicity or overtreatment with phototherapy and/or exchange transfusion. Clinicians should rely on expert consensus opinions to guide timely and effective interventions until there is better evidence to refine bilirubin-induced neurologic dysfunction or benefits of bilirubin. In this article, we review the evolving evidence for bilirubin-induced brain injury in preterm infants and highlight the clinical approaches that minimize the risk of bilirubin neurotoxicity. PMID:27235203

  13. Utilizing Federal Reporting Requirements to Generate Useful Data at the Local Level: Creating an Open-Book Data Base.

    ERIC Educational Resources Information Center

    Carifio, James; Shwedel, Allan

    Various procedures, technologies, and products were developed by the Massachusetts Board of Regents and the Massachusetts Community Colleges in implementing the student followup component of the Vocational Education Data System (VEDS). The Board of Regents took the lead in coordinating the VEDS followup study among the 15 state-supported community…

  14. Structure-permeability relationship analysis of the permeation barrier properties of the stratum corneum and viable epidermis/dermis of rat skin.

    PubMed

    Yamaguchi, Koji; Mitsui, Tetsuya; Aso, Yoshinori; Sugibayashi, Kenji

    2008-10-01

    The purpose of this study was to evaluate structure-permeability relationships for chemicals through stratum corneum (SC) and viable epidermis/dermis (VED). In vitro skin permeation of ten compounds through excised rat skin was analyzed based on a two-layer diffusion model and the diffusion coefficients in SC (D(SC)) and VED (D(VED)) were determined. The relationships between the permeation parameters and the physicochemical parameters (octanol-water partition coefficient (log K(o/w)), and hydrogen bond donor number (HBD)) of the compounds were analyzed. D(SC) increased as lipophilicity increased, whereas D(VED) decreased for log K(o/w) > 2. Increases in log K(o/w) caused a decrease in the permeability coefficient from SC through VED (P(VED/SC)) for log K(o/w) > 1. The simulation study suggests that the in vitro skin permeation of a highly lipophilic compound is strongly controlled by skin thickness due to low diffusivity in VED. The present study suggests that VED act as a considerable permeation barrier for highly lipophilic compounds due to low diffusivity. PMID:18228598

  15. Vacuum therapy in penile rehabilitation after radical prostatectomy: review of hemodynamic and antihypoxic evidence

    PubMed Central

    Qian, Sheng-Qiang; Gao, Liang; Wei, Qiang; Yuan, Jiuhong

    2016-01-01

    Generally, hypoxia is a normal physiological condition in the flaccid penis, which is interrupted by regular nocturnal erections in men with normal erectile function.1 Lack of spontaneous and nocturnal erections after radical prostatectomy due to neuropraxia results in persistent hypoxia of cavernosal tissue, which leads to apoptosis and degeneration of cavernosal smooth muscle fibers. Therefore, overcoming hypoxia is believed to play a crucial role during neuropraxia. The use of a vacuum erectile device (VED) in penile rehabilitation is reportedly effective and may prevent loss of penile length. The corporal blood after VED use is increased and consists of both arterial and venous blood, as revealed by color Doppler sonography and blood gas analysis. A similar phenomenon was observed in negative pressure wound therapy (NPWT). However, NPWT employs a lower negative pressure than VED, and a hypoperfused zone, which increases in response to negative pressure adjacent to the wound edge, was observed. Nonetheless, questions regarding ideal subatmospheric pressure levels, modes of action, and therapeutic duration of VED remain unanswered. Moreover, it remains unclear whether a hypoperfused zone or PO2 gradient appears in the penis during VED therapy. To optimize a clinical VED protocol in penile rehabilitation, further research on the mechanism of VED, especially real-time PO2 measurements in different parts of the penis, should be performed. PMID:26289397

  16. Vacuum therapy in penile rehabilitation after radical prostatectomy: review of hemodynamic and antihypoxic evidence.

    PubMed

    Qian, Sheng-Qiang; Gao, Liang; Wei, Qiang; Yuan, Jiuhong

    2016-01-01

    Generally, hypoxia is a normal physiological condition in the flaccid penis, which is interrupted by regular nocturnal erections in men with normal erectile function. [1] Lack of spontaneous and nocturnal erections after radical prostatectomy due to neuropraxia results in persistent hypoxia of cavernosal tissue, which leads to apoptosis and degeneration of cavernosal smooth muscle fibers. Therefore, overcoming hypoxia is believed to play a crucial role during neuropraxia. The use of a vacuum erectile device (VED) in penile rehabilitation is reportedly effective and may prevent loss of penile length. The corporal blood after VED use is increased and consists of both arterial and venous blood, as revealed by color Doppler sonography and blood gas analysis. A similar phenomenon was observed in negative pressure wound therapy (NPWT). However, NPWT employs a lower negative pressure than VED, and a hypoperfused zone, which increases in response to negative pressure adjacent to the wound edge, was observed. Nonetheless, questions regarding ideal subatmospheric pressure levels, modes of action, and therapeutic duration of VED remain unanswered. Moreover, it remains unclear whether a hypoperfused zone or PO 2 gradient appears in the penis during VED therapy. To optimize a clinical VED protocol in penile rehabilitation, further research on the mechanism of VED, especially real-time PO 2 measurements in different parts of the penis, should be performed. PMID:26289397

  17. Functional and hierarchical interactions among zebrafish vox/vent homeobox genes.

    PubMed

    Gilardelli, Claudio N; Pozzoli, Ombretta; Sordino, Paolo; Matassi, Giorgio; Cotelli, Franco

    2004-07-01

    The vertebrate Vox/Vent family of transcription factors plays a crucial role in the establishment of the dorsoventral (DV) axis, by repressing organizer genes such as bozozok/dharma, goosecoid, and chordino. In Danio rerio (zebrafish), members of the vox/vent gene family (vox/vega1, vent/vega2, and ved) are thought to share expression patterns and functional properties. Bringing novel insights in the differential activity of the zebrafish vox/vent genes, we propose a critical role for the ved gene in DV patterning of vertebrate embryos. ved is not only expressed as a maternal gene, but it also appears to function as a repressor of dorsal factors involved in organizer formation. At early- and mid-gastrula stage, ved appears to be finely controlled by antagonist crosstalks in a complex regulatory network, involving gradients of bone morphogenetic protein (BMP) activity, dorsal factors, and vox/vent family members. We show that ved transcripts are ventrally restricted by BMP factors such as bmp2b, bmp7, smad5, and alk8, and by dorsal factors (chd and gsc). Alteration of ved expression in both vox and vent deletion mutants and vox and vent mRNAs-injected embryos, suggests that vox and vent function downstream of BMP signaling to negatively regulate ved expression. This inhibitory role is emphasized by a vox and vent redundant activity, compared with single gene effects. PMID:15188434

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

    PubMed

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

    2009-01-01

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

  19. Spontaneous decidualization in pseudopregnant rats with vitamin E deficiency.

    PubMed

    Lang, Nan; Wu, Bin; He, Bin; Wang, Lili; Wang, Jiedong

    2016-05-13

    Successful implantation of an embryo requires adequate depth of invasion in the endometrium, which depends upon decidualization. The aim of the present study was to elucidate why humans experience spontaneous decidualization and menstruation while most other mammals do not. We established a spontaneous decidualization model in pseudopregnant rats with vitamin E deficiency (VED) to investigate mechanisms associated with spontaneous decidualization. Vaginal smears were used to monitor bleeding while vitamin E levels were analyzed with a commercial vitamin E assay kit. Trypan blue staining was used to observe the implantation site at 5.5 days post-coitum (dpc). Uterine morphology, estradiol (E2) and progesterone levels, and the anti-oxidation system were evaluated at 5.5, 7.5, and 9.5 dpc. The proportion of rats in the VED group exhibiting endometrial bleeding gradually increased (5.9%, 32.3%, and 50%) over three consecutive cycles of pseudopregnancy. Vitamin E levels in the VED group were markedly lower compared to the control group in both the plasma and uterus, while the level of vitamin E in the liver did not differ between the control and VED groups. Spontaneous decidualization in the VED group was validated by histological examination and immunohistochemistry. At 5.5 dpc, the mean serum E2 level in the VED group was more than twice that of the control group. The mean total anti-oxidizing capability, catalase level, and glutathione peroxidase activity were significantly reduced in the decidualized portion of the VED group compared to controls, while the malondialdehyde level was also significantly higher in the decidualized portion of the VED group. We hypothesize that the E2 surge at 5.5 dpc and increasing levels of reactive oxygen species are responsible for spontaneous decidualization in VED rats. PMID:27033606

  20. Mechanisms underlying benign and reversible unconjugated hyperbilirubinemia observed with faldaprevir administration in hepatitis C virus patients.

    PubMed

    Sane, Rucha S; Steinmann, Gerhard G; Huang, Qihong; Li, Yongmei; Podila, Lalitha; Mease, Kirsten; Olson, Stephen; Taub, Mitchell E; Stern, Jerry O; Nehmiz, Gerhard; Böcher, Wulf O; Asselah, Tarik; Tweedie, Donald

    2014-11-01

    Faldaprevir, an investigational agent for hepatitis C virus treatment, is well tolerated but associated with rapidly reversible, dose-dependent, clinically benign, unconjugated hyperbilirubinemia. Multidisciplinary preclinical and clinical studies were used to characterize mechanisms underlying this hyperbilirubinemia. In vitro, faldaprevir inhibited key processes involved in bilirubin clearance: UDP glucuronosyltransferase (UGT) 1A1 (UGT1A1) (IC50 0.45 µM), which conjugates bilirubin, and hepatic uptake and efflux transporters, organic anion-transporting polypeptide (OATP) 1B1 (IC50 0.57 µM), OATP1B3 (IC50 0.18 µM), and multidrug resistance-associated protein (MRP) 2 (IC50 6.2 µM), which transport bilirubin and its conjugates. In rat and human hepatocytes, uptake and biliary excretion of [(3)H]bilirubin and/or its glucuronides decreased on coincubation with faldaprevir. In monkeys, faldaprevir (≥20 mg/kg per day) caused reversible unconjugated hyperbilirubinemia, without hemolysis or hepatotoxicity. In clinical studies, faldaprevir-mediated hyperbilirubinemia was predominantly unconjugated, and levels of unconjugated bilirubin correlated with the UGT1A1*28 genotype. The reversible and dose-dependent nature of the clinical hyperbilirubinemia was consistent with competitive inhibition of bilirubin clearance by faldaprevir, and was not associated with liver toxicity or other adverse events. Overall, the reversible, unconjugated hyperbilirubinemia associated with faldaprevir may predominantly result from inhibition of bilirubin conjugation by UGT1A1, with inhibition of hepatic uptake of bilirubin also potentially playing a role. Since OATP1B1/1B3 are known to be involved in hepatic uptake of circulating bilirubin glucuronides, inhibition of OATP1B1/1B3 and MRP2 may underlie isolated increases in conjugated bilirubin. As such, faldaprevir-mediated hyperbilirubinemia is not associated with any liver injury or toxicity, and is considered to result from decreased

  1. [Physiopathology of neonatal hyperbilirubinemia].

    PubMed

    Vert, P

    1998-09-01

    The most important steps of bilirubin metabolism involved in the pathophysiology of neonatal hyperbilirubinemia are: 1) hemoglobin degradation by heme oxygenase; 2) bilirubin binding to serum albumin; 3) bilirubin conjugation to acid glucoronic by glucoronyl transferase. Progress in the knowledge of these metabolic steps allows to understanding of why massive hemolysis, infections, hypoxia and prematurity increase the risk of kernicterus and therefore justify adapted preventive and therapeutic measures. PMID:9789638

  2. Diagnosing Jaundice by Eye-Outpatient Assessment of Conjunctival Icterus in the Newborn.

    PubMed

    Maisels, M Jeffrey; Coffey, Mary P; Gendelman, Brian; Smyth, Mary; Kendall, Ada; Clune, Sarah; Coleman, Kimberlee; McManus, Sharon

    2016-05-01

    In pediatric office practices, we compared transcutaneous bilirubin levels in 689 newborns, age 3-10 days, with and without conjunctival icterus. In this age range, and in the absence of other clinical or laboratory indications, the presence of conjunctival icterus does not imply the need to measure the transcutaneous bilirubin or serum bilirubin level, but the absence of conjunctival icterus helps to rule out significant hyperbilirubinemia. PMID:26898809

  3. The field of the vertical electric dipole immersed in the heterogeneous half-space

    NASA Astrophysics Data System (ADS)

    Barsukov, P. O.; Fainberg, E. B.

    2014-07-01

    The field of the vertical electric dipole (VED) immersed in the heterogeneous conductive halfspace (sea) is analyzed in time domain. In the near field of the source, the amplitudes of the electric and magnetic components of the field are proportional to power 3/2 and power 5/2 of the conductivity of the medium, respectively. After termination of the transmitter pulse, all the VED components decay with time as ˜1/ t 5/2. The possibility of applying the VED field for estimating the electrical properties of the offshore geological sections is demonstrated.

  4. Finiteness of the vacuum energy density in quantum electrodynamics

    NASA Astrophysics Data System (ADS)

    Manoukian, Edward B.

    1983-03-01

    Recent interest in the finiteness problem of the vacuum energy density (VED) in finite QED has motivated us to reexamine this problem in the light of an analysis we have carried out earlier. By a loopwise summation procedure, supplemented by a renormalization-group analysis, we study the finiteness of the VED with α, the renormalized fine-structure constant, fixed in the process as the (infinite order) zero of the eigenvalue condition F[1](x)|x=α=0∞, and with the electron mass totally dynamical of origin. We propose a possible finite solution for the VED in QED which may require only one additional eigenvalue condition for α.

  5. Spontaneous Splenic Rupture in Vascular Ehlers-Danlos Syndrome.

    PubMed

    Batagini, Nayara Cioffi; Gornik, Heather; Kirksey, Lee

    2015-01-01

    Vascular Ehlers-Danlos Syndrome (VEDS) is a rare autosomal dominant collagen vascular disorder. Different from other Ehler-Danlos Syndrome subtypes, VEDS has poor prognosis due to severe fragility of connective tissues and association with life-threatening vascular and gastrointestinal complications. Spontaneous splenic rupture is a rare but hazardous complication related to this syndrome. To date, only 2 cases have been reported in the literature. Here we present another case of this uncommon complication, occurring in a 54-year-old woman in clinical follow-up for VEDS who presented with sudden onset of abdominal pain and hypotension. PMID:26323967

  6. Evaluation of digital halftones image by vector error diffusion

    NASA Astrophysics Data System (ADS)

    Kouzaki, Masahiro; Itoh, Tetsuya; Kawaguchi, Takayuki; Tsumura, Norimichi; Haneishi, Hideaki; Miyake, Yoichi

    1998-12-01

    The vector error diffusion (VED) method is applied to proudce the digital halftone images by an electrophotographic printer with 600 dpi. Objective image quality of those obtained images is evaluated and analyzed. As a result, in the color reproduction of halftone image by the VED method, it was clear that there are large color difference between target color and printed color typically in the mid-tone colors. We consider it is due to the printer properties including dot-gain. It was also clear that the color noise of the VED method is larger compared with that of the conventional scalar error diffusion method in some patches. It was remarkable that ununiform patterns are generated by the VED method.

  7. [Abdominal ischemia and lesions of the pancreas].

    PubMed

    Myshanych, T V; Moskal', O M; Arkhiĭ, E Ĭ; Sozoniuk, O V

    2014-01-01

    The analysis of the results of 50 patients with diseases of coronary heart disease (25 pers.) And chronic pancreatitis (25 people) are submitted. Along with the standard test from these patients underwent Doppler-ultrasonography of abdominal aorta and its visceral branches. Conclusions: A characteristic feature of Doppler indices in AIC is to reduce Vps and Ved, and PI BbA, increase Vps, Ved, IR and PI after exercise in chBA, chC and BbA. At patients with CP with IHD feature is the increase in Ved and IR in the chC, and Ved and PI in BbA under act of loading Bleed a feature at CP with IHD must be taken into account for optimization of treatment of IHD at CP. PMID:25796868

  8. Effect of agmatine on experimental vascular endothelial dysfunction.

    PubMed

    Nader, M A; Gamiel, N M; El-Kashef, H; Zaghloul, M S

    2016-05-01

    This study was designed to investigate the effect of agmatine sulfate (AG, CAS2482-00-0) in nicotine (NIC)-induced vascular endothelial dysfunction (VED) in rabbits. NIC was administered to produce VED in rabbits with or without AG for 6 weeks. Serum lipid profile, serum thiobarbituric acid reactive substances, reduced glutathione, superoxide dismutase generation, serum nitrite/nitrate, serum vascular cellular adhesion molecule-1 (VCAM-1), and aortic nuclear factor κB (NF-κB) levels were analyzed.Treatment with AG markedly improves lipid profile and prevented NIC-induced VED and oxidative stress. The mechanism of AG in improving NIC-induced VED may be due to the significant reduction in serum VCAM-1 levels and aortic NF-κB. Thus, it may be concluded that AG reduces the oxidative stress, nitric oxide production, VCAM-1 levels, and aortic NF-κB expression, thereby consequently improving the integrity of vascular endothelium. PMID:26424770

  9. Oral phenotype and scoring of vascular Ehlers–Danlos syndrome: a case–control study

    PubMed Central

    Frank, Michael; Gogly, Bruno; Golmard, Lisa; Naveau, Adrien; Chérifi, Hafida; Emmerich, Joseph; Gaultier, Frédérick; Berdal, Ariane; Jeunemaitre, Xavier; Fournier, Benjamin P J

    2012-01-01

    Objective Vascular Ehlers–Danlos syndrome (vEDS) is a rare genetic condition related to mutations in the COL3A1 gene, responsible of vascular, digestive and uterine accidents. Difficulty of clinical diagnosis has led to the design of diagnostic criteria, summarised in the Villefranche classification. The goal was to assess oral features of vEDS. Gingival recession is the only oral sign recognised as a minor diagnostic criterion. The authors aimed to check this assumption since bibliographical search related to gingival recession in vEDS proved scarce. Design Prospective case–control study. Setting Dental surgery department in a French tertiary hospital. Participants 17 consecutive patients with genetically proven vEDS, aged 19–55 years, were compared with 46 age- and sex-matched controls. Observations Complete oral examination (clinical and radiological) with standardised assessment of periodontal structure, temporomandibular joint function and dental characteristics were performed. COL3A1 mutations were identified by direct sequencing of genomic or complementary DNA. Results Prevalence of gingival recession was low among patients with vEDS, as for periodontitis. Conversely, patients showed marked gingival fragility, temporomandibular disorders, dentin formation defects, molar root fusion and increased root length. After logistic regression, three variables remained significantly associated to vEDS. These variables were integrated in a diagnostic oral score with 87.5% and 97% sensitivity and specificity, respectively. Conclusions Gingival recession is an inappropriate diagnostic criterion for vEDS. Several new specific oral signs of the disease were identified, whose combination may be of greater value in diagnosing vEDS. PMID:22492385

  10. A Product of Heme Catabolism Modulates Bacterial Function and Survival

    PubMed Central

    Nobles, Christopher L.; Green, Sabrina I.; Maresso, Anthony W.

    2013-01-01

    Bilirubin is the terminal metabolite in heme catabolism in mammals. After deposition into bile, bilirubin is released in large quantities into the mammalian gastrointestinal (GI) tract. We hypothesized that intestinal bilirubin may modulate the function of enteric bacteria. To test this hypothesis, we investigated the effect of bilirubin on two enteric pathogens; enterohemorrhagic E. coli (EHEC), a Gram-negative that causes life-threatening intestinal infections, and E. faecalis, a Gram-positive human commensal bacterium known to be an opportunistic pathogen with broad-spectrum antibiotic resistance. We demonstrate that bilirubin can protect EHEC from exogenous and host-generated reactive oxygen species (ROS) through the absorption of free radicals. In contrast, E. faecalis was highly susceptible to bilirubin, which causes significant membrane disruption and uncoupling of respiratory metabolism in this bacterium. Interestingly, similar results were observed for other Gram-positive bacteria, including B. cereus and S. aureus. A model is proposed whereby bilirubin places distinct selective pressure on enteric bacteria, with Gram-negative bacteria being protected from ROS (positive outcome) and Gram-positive bacteria being susceptible to membrane disruption (negative outcome). This work suggests bilirubin has differential but biologically relevant effects on bacteria and justifies additional efforts to determine the role of this neglected waste catabolite in disease processes, including animal models. PMID:23935485

  11. Why should we care about neonatal hyperbilirubinemia in 2011?

    PubMed

    Raimondi, Francesco; Maffucci, Rosalba; Milite, Paola; Ferrara, Teresa; Borrelli, Angela Carla; Sodano, Angela; Capasso, Letizia

    2011-10-01

    Recent research links serum bilirubin levels to a positive function in human health. Yet in the neonate hyperbilirubinemia is associated to damage to the CNS and beyond. This article summarizes the evidence for the double edged role of bilirubin with a focus on the neonatal period. Also we briefly describe some of the current shortcomings in the treatment of neonatal hyperbilirubinemia. PMID:21942598

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

    PubMed Central

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

    2015-01-01

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

  13. REGULATION OF RAT HEPATIC DELTA-AMINOLEVULINIC ACID SYNTHETASE AND HEME OXYGENASE ACTIVITIES: EVIDENCE FOR CONTROL BY HEME AND AGAINST MEDIATION BY PROSTHETIC IRON

    EPA Science Inventory

    The effects of in vivo administration of 6 compounds on the activity of delta-aminolevulinic acid (ALA) synthetase and heme oxygenase were determined. The order of decreasing potency in reducing ALA synthetase activity was heme, bilirubin, protoporphyrin IX, bilirubin dimethyl es...

  14. [Simultaneous long-term measurement of duodenogastric reflux and gastroduodenal motility].

    PubMed

    Thomas, H; Wilhelm, L; Petermann, J; Rosenbaum, K D; Lorenz, D

    1997-06-01

    We combined a newly developed ambulatory fiberoptic system for detecting intragastric bilirubin (Bilitec 2000, Synectics Medical Inc., Sweden) with prolonged measurement of gastroduodenal motility in 10 healthy volunteers and 10 patients followed BI resection. Circadian intragastric bilirubin exposure and the total number of tremendous changes of bilirubin absorption (more than 20%, over a period of at least 5 min) were significantly increased in the BI-resected patients (P < 0.05). In patients the interdigestive motility cycle (IMC) was characterized by the appearance of several types of abnormally propagated phase III activity fronts. Of the tremendous increases of bilirubin absorption in the patient group, 90.1% were associated with abnormally propagated phase III activity fronts. In cases of increased duodenogastric reflux, the combination of ambulatory intragastric bilirubin measurement and long-term manometry seems to be feasible to assess motility and reflux simultaneously. PMID:9324442

  15. Vascular Ehlers-Danlos syndrome without the characteristic facial features: a case report.

    PubMed

    Inokuchi, Ryota; Kurata, Hideaki; Endo, Kiyoshi; Kitsuta, Yoichi; Nakajima, Susumu; Hatamochi, Atsushi; Yahagi, Naoki

    2014-12-01

    As a type of Ehlers-Danlos syndrome (EDS), vascular EDs (vEDS) is typified by a number of characteristic facial features (eg, large eyes, small chin, sunken cheeks, thin nose and lips, lobeless ears). However, vEDs does not typically display hypermobility of the large joints and skin hyperextensibility, which are features typical of the more common forms of EDS. Thus, colonic perforation or aneurysm rupture may be the first presentation of the disease. Because both complications are associated with a reduced life expectancy for individuals with this condition, an awareness of the clinical features of vEDS is important. Here, we describe the treatment of vEDS lacking the characteristic facial attributes in a 24-year-old healthy man who presented to the emergency room with abdominal pain. Enhanced computed tomography revealed diverticula and perforation in the sigmoid colon. The lesion of the sigmoid colon perforation was removed, and Hartmann procedure was performed. During the surgery, the control of bleeding was required because of vascular fragility. Subsequent molecular and genetic analysis was performed based on the suspected diagnosis of vEDS. These analyses revealed reduced type III collagen synthesis in cultured skin fibroblasts and identified a previously undocumented mutation in the gene for a1 type III collagen, confirming the diagnosis of vEDS. After eliciting a detailed medical profile, we learned his mother had a history of extensive bruising since childhood and idiopathic hematothorax. Both were prescribed oral celiprolol. One year after admission, the patient was free of recurrent perforation. This case illustrates an awareness of the clinical characteristics of vEDS and the family history is important because of the high mortality from this condition even in young people. Importantly, genetic assays could help in determining the surgical procedure and offer benefits to relatives since this condition is inherited in an autosomal dominant manner. PMID

  16. Vascular Ehlers-Danlos Syndrome Without the Characteristic Facial Features

    PubMed Central

    Inokuchi, Ryota; Kurata, Hideaki; Endo, Kiyoshi; Kitsuta, Yoichi; Nakajima, Susumu; Hatamochi, Atsushi; Yahagi, Naoki

    2014-01-01

    Abstract As a type of Ehlers-Danlos syndrome (EDS), vascular EDs (vEDS) is typified by a number of characteristic facial features (eg, large eyes, small chin, sunken cheeks, thin nose and lips, lobeless ears). However, vEDs does not typically display hypermobility of the large joints and skin hyperextensibility, which are features typical of the more common forms of EDS. Thus, colonic perforation or aneurysm rupture may be the first presentation of the disease. Because both complications are associated with a reduced life expectancy for individuals with this condition, an awareness of the clinical features of vEDS is important. Here, we describe the treatment of vEDS lacking the characteristic facial attributes in a 24-year-old healthy man who presented to the emergency room with abdominal pain. Enhanced computed tomography revealed diverticula and perforation in the sigmoid colon. The lesion of the sigmoid colon perforation was removed, and Hartmann procedure was performed. During the surgery, the control of bleeding was required because of vascular fragility. Subsequent molecular and genetic analysis was performed based on the suspected diagnosis of vEDS. These analyses revealed reduced type III collagen synthesis in cultured skin fibroblasts and identified a previously undocumented mutation in the gene for a1 type III collagen, confirming the diagnosis of vEDS. After eliciting a detailed medical profile, we learned his mother had a history of extensive bruising since childhood and idiopathic hematothorax. Both were prescribed oral celiprolol. One year after admission, the patient was free of recurrent perforation. This case illustrates an awareness of the clinical characteristics of vEDS and the family history is important because of the high mortality from this condition even in young people. Importantly, genetic assays could help in determining the surgical procedure and offer benefits to relatives since this condition is inherited in an autosomal dominant

  17. Hyperbilirubinemia Diminishes Respiratory Drive in a Rat Pup Model

    PubMed Central

    Mesner, Oded; Miller, Martha J.; Iben, Sabine C.; Kc, Prabha; Mayer, Catherine A.; A. Haxhiu, Musa; Martin, Richard J.

    2008-01-01

    Although apnea is common in premature babies, there is a paucity of information concerning the pathophysiologic basis of these episodes and their relationship to other perinatal conditions such as hyperbilirubinemia. Unconjugated hyperbilirubinemia in premature infants, even in moderately high levels, may cause encephalopathy affecting brainstem functions and has been linked to increased incidence of apnea in these infants. Thus, there is a need to clarify mechanisms by which bilirubin may alter respiratory control and induce apnea of prematurity. In this study, bilirubin or placebo was infused intravenously in 9 day-old rat pups, n=36. Serum hyperbilirubinemia peaked in the first hours after bilirubin infusion. Twenty four hours after bilirubin infusion, respiration was recorded by plethysmography at rest and under hypercapnic and hypoxic conditions. In treated pups, minute ventilation on room air was significantly reduced, hyperventilatory response to CO2 was blunted and hypoxic ventilatory depression was increased, as compared to placebo injected rat pups. Brainstem bilirubin deposition and immunoreactivity to bilirubin was detected in the brainstem on histologic analysis. We speculate that high serum bilirubin levels may cause prolonged inhibition of brainstem autonomic function and that this could underlie the exacerbation of apnea noted in premature babies who have experienced jaundice. PMID:18458654

  18. Recipient Hyperbilirubinemia May Reduce Ischemia-Reperfusion Injury but Fails to Improve Outcome in Clinical Liver Transplantation

    PubMed Central

    Oltean, Mihai; Barrenäs, Christian; Martins, Paulo Ney; Herlenius, Gustaf; Gustafsson, Bengt; Friman, Styrbjörn; Bennet, William

    2016-01-01

    Background. Exogenous bilirubin may reduce experimental ischemia-reperfusion injury (IRI) due to its antioxidant properties. We studied if early graft exposure to high bilirubin levels in the recipient affects the early IRI and outcomes after liver transplantation (LTx). Methods. In 427 LTx patients, the AUROC curve based on bilirubin and AST at day 1 identified a cutoff of 2.04 mg/dL for the recipient pretransplant bilirubin. Recipients were grouped as having low (group L, n = 152) or high (group H, n = 275) bilirubin. Both groups had similar donor-related variables (age, preservation time, donor BMI > 28, and donor risk index (DRI)). Results. Alanine (ALT) and aspartate (AST) aminotransferase levels were higher in group L at day 1; ALT levels remained higher at day 2 in group L. LTx from high risk donors (DRI > 2) revealed a trend towards lower transaminases during the first two days after transplantation in group H. One month and 1-year patient survival were similar in groups L and H. High preoperative bilirubin did not affect the risk for early graft dysfunction (EGD), death, or graft loss during the first year after transplantation nor the incidence of acute rejection. LTx using donors with DRI > 2 resulted in similar rates of EGD in both groups. Conclusion. Increased bilirubin appears to reduce the early IRI after LTx yet this improvement was insufficient to improve the clinical outcome.

  19. Prolonged Hyperbilirubinemia in a Neonate with a Novel Mutation in the UDP-glucuronosyltransferase 1A1 Gene.

    PubMed

    Mu, Shu-Chi; Chen, Yi-Ling; Tsai, Li-Yi; Shih, Yung-Luen; Chen, En-Sung; Huang, Ching-Shan

    2016-01-01

    The total bilirubin value of a male infant was 385 μmol/l on day 5. Liver function test results were normal and there was no evidence of sepsis and no hemolysis reaction. Phototherapy was administered and on day 8 the patient's total bilirubin level was 255 μmol/l. Intermittent episodes of hyperbilirubinemia occurred without phototherapy, with the total bilirubin level reaching 335 μmol/l on day 19. A 3-day regimen of phenobarbital was administered and on day 24 his total bilirubin level was 180 μmol/l. The patient was discharged. At the age of 2 months, the total bilirubin value was 27 μmol/l. His direct bilirubin value was <15% of total bilirubin in every determination. A family study of the UDP-glucuronosyltransferase(UGT)1A1 gene showed that the infant carries a homozygous mutation at nucleotide -3279 plus compound heterozygous mutations at nucleotides 782 and 1091. The mutation at nucleotide 782 is a novel finding. Gilbert's syndrome was diagnosed. PMID:26859599

  20. Endogenous production of carbon monoxide in normal and erythroblastotic newborn infants

    PubMed Central

    Maisels, M. Jeffrey; Pathak, Ambadas; Nelson, Nicholas M.; Nathan, David G.; Smith, Clement A.

    1971-01-01

    The endogenous production of carbon monoxide (˙VCO) in newborn infants was measured by serial determinations of blood carboxyhemoglobin during rebreathing in a closed system. Mean ˙VCO in nine full-term infants was 13.7 ±3.6 μl CO/kg per hr (SD), and in four erythroblastotic infants ˙VCO ranged from 37 to 154 μl CO/kg per hr preceding exchange transfusion. Mean red cell life-span (MLS) and total bilirubin production were calculated from ˙VCO. MLS in normal newborns was 88 ±15 days (SD), and bilirubin production was 8.5 ±2.3 mg/kg per 24 hr. This is more than twice the amount of bilirubin normally produced in the adult per kilogram of body weight. Normal infants achieved a net excretion of bilirubin of at least 5.6 ±2.3 mg/kg per 24 hr (SD) as calculated from the bilirubin production and the measured rise in serum bilirubin concentration. The measurement of ˙VCO should prove valuable in the study of red blood cell survival and bilirubin metabolism in the newborn infant. Images PMID:5543875

  1. Clinical and Pharmacogenetic Factors Affecting Neonatal Bilirubinemia Following Atazanavir Treatment of Mothers During Pregnancy

    PubMed Central

    Huang, Shu-Pang; Conradie, Francesca; Zorrilla, Carmen D.; Josipovic, Deirdre; Botes, Mariëtte; Osiyemi, Olayemi; Hardy, Hélène; Bertz, Richard; McGrath, Donnie

    2013-01-01

    Abstract A theoretical concern exists that atazanavir (ATV) use during pregnancy may exacerbate physiologic neonatal hyperbilirubinemia. The aim of this substudy was to evaluate patterns of neonatal bilirubin following ATV/ritonavir (RTV) treatment of pregnant mothers and clinical and pharmacogenetic factors that may correlate. The design involved a subanalysis of study AI424182, a multicenter, open-label, prospective, single-arm Phase I study. The study had two treatment arms: (1) ATV/RTV 300/100 mg once daily or (2) ATV/RTV 400/100 mg once daily, both in combination with zidovudine/lamivudine 300/150 mg twice daily. Total bilirubin was assessed at baseline, each visit, and delivery day for mothers and on days 1 (delivery day), 3, 5, and 7 and weeks 2 and 6 for neonates. Blood samples were obtained for UGT1A1 genotyping and ATV cord blood concentration. Bilirubin elevation of any grade occurred in 14/40 neonates (35%). All Grade 3 to 4 bilirubin abnormalities (n=7) occurred after day 14. The pattern of neonatal bilirubin levels reported was consistent with neonatal physiologic elevations of bilirubin. Little correlation was observed between either maternal bilirubin levels over the last 4 weeks of pregnancy (including delivery) or ATV cord concentration and neonatal bilirubin. There was a significant association between UGT1A1 genotype and bilirubin grade in the maternal population (p=0.0006) but not neonates (p=0.49). Neither neonatal UGT1A1 genotype nor cord blood ATV concentration is a good predictor of neonatal hyperbilirubinemia. ATV/RTV treatment of mothers does not appear to exacerbate neonatal physiologic hyperbilirubinemia. PMID:23782005

  2. Clinical and pharmacogenetic factors affecting neonatal bilirubinemia following atazanavir treatment of mothers during pregnancy.

    PubMed

    Eley, Timothy; Huang, Shu-Pang; Conradie, Francesca; Zorrilla, Carmen D; Josipovic, Deirdre; Botes, Mariëtte; Osiyemi, Olayemi; Hardy, Hélène; Bertz, Richard; McGrath, Donnie

    2013-10-01

    A theoretical concern exists that atazanavir (ATV) use during pregnancy may exacerbate physiologic neonatal hyperbilirubinemia. The aim of this substudy was to evaluate patterns of neonatal bilirubin following ATV/ritonavir (RTV) treatment of pregnant mothers and clinical and pharmacogenetic factors that may correlate. The design involved a subanalysis of study AI424182, a multicenter, open-label, prospective, single-arm Phase I study. The study had two treatment arms: (1) ATV/RTV 300/100 mg once daily or (2) ATV/RTV 400/100 mg once daily, both in combination with zidovudine/lamivudine 300/150 mg twice daily. Total bilirubin was assessed at baseline, each visit, and delivery day for mothers and on days 1 (delivery day), 3, 5, and 7 and weeks 2 and 6 for neonates. Blood samples were obtained for UGT1A1 genotyping and ATV cord blood concentration. Bilirubin elevation of any grade occurred in 14/40 neonates (35%). All Grade 3 to 4 bilirubin abnormalities (n=7) occurred after day 14. The pattern of neonatal bilirubin levels reported was consistent with neonatal physiologic elevations of bilirubin. Little correlation was observed between either maternal bilirubin levels over the last 4 weeks of pregnancy (including delivery) or ATV cord concentration and neonatal bilirubin. There was a significant association between UGT1A1 genotype and bilirubin grade in the maternal population (p=0.0006) but not neonates (p=0.49). Neither neonatal UGT1A1 genotype nor cord blood ATV concentration is a good predictor of neonatal hyperbilirubinemia. ATV/RTV treatment of mothers does not appear to exacerbate neonatal physiologic hyperbilirubinemia. PMID:23782005

  3. Novel diode-based laser system for combined transcutaneous monitoring and computer-controlled intermittent treatment of jaundiced neonates

    NASA Astrophysics Data System (ADS)

    Hamza, Mostafa; El-Ahl, Mohammad H. S.; Hamza, Ahmad M.

    2001-06-01

    The high efficacy of laser phototherapy combined with transcutaneous monitoring of serum bilirubin provides optimum safety for jaundiced infants from the risk of bilirubin encephalopathy. In this paper the authors introduce the design and operating principles of a new laser system that can provide simultaneous monitoring and treatment of several jaundiced babies at one time. The new system incorporates diode-based laser sources oscillating at selected wavelengths to achieve both transcutaneous differential absorption measurements of bilirubin concentration in addition to the computer controlled intermittent laser therapy through a network of optical fibers. The detailed description and operating characteristics of this system are presented.

  4. Therapeutic Effect of Agaricus brasiliensis on Phenylhydrazine-Induced Neonatal Jaundice in Rats

    PubMed Central

    Zhang, Lan; Yuan, Bo; Wang, HuiPing; Gao, Ya

    2015-01-01

    The present study was designed to investigate the effect of Agaricus brasiliensis extract (ABE) on phenylhydrazine-induced neonatal jaundice in rats. Administration of ABE dose-dependently reduced the elevated bilirubin level induced by phenylhydrazine. It can be somewhat supported from the results of in vitro bilirubin degradation experiment. ABE treatment also reduced the total antioxidant status (TAOS), cascade O2−/SOD, level of NF-κB protein, and adrenomedullin (AM). Overall, the results of this study demonstrated that Agaricus brasiliensis extract may be beneficial to reducing bilirubin level without causing hepatotoxicity in neonatal jaundice. PMID:25883968

  5. Therapeutic effect of Agaricus brasiliensis on phenylhydrazine-induced neonatal jaundice in rats.

    PubMed

    Zhang, Lan; Yuan, Bo; Wang, HuiPing; Gao, Ya

    2015-01-01

    The present study was designed to investigate the effect of Agaricus brasiliensis extract (ABE) on phenylhydrazine-induced neonatal jaundice in rats. Administration of ABE dose-dependently reduced the elevated bilirubin level induced by phenylhydrazine. It can be somewhat supported from the results of in vitro bilirubin degradation experiment. ABE treatment also reduced the total antioxidant status (TAOS), cascade O2(-)/SOD, level of NF-κB protein, and adrenomedullin (AM). Overall, the results of this study demonstrated that Agaricus brasiliensis extract may be beneficial to reducing bilirubin level without causing hepatotoxicity in neonatal jaundice. PMID:25883968

  6. Vessel enhancing diffusion: a scale space representation of vessel structures.

    PubMed

    Manniesing, Rashindra; Viergever, Max A; Niessen, Wiro J

    2006-12-01

    A method is proposed to enhance vascular structures within the framework of scale space theory. We combine a smooth vessel filter which is based on a geometrical analysis of the Hessian's eigensystem, with a non-linear anisotropic diffusion scheme. The amount and orientation of diffusion depend on the local vessel likeliness. Vessel enhancing diffusion (VED) is applied to patient and phantom data and compared to linear, regularized Perona-Malik, edge and coherence enhancing diffusion. The method performs better than most of the existing techniques in visualizing vessels with varying radii and in enhancing vessel appearance. A diameter study on phantom data shows that VED least affects the accuracy of diameter measurements. It is shown that using VED as a preprocessing step improves level set based segmentation of the cerebral vasculature, in particular segmentation of the smaller vessels of the vasculature. PMID:16876462

  7. Spontaneous Dissection of the Renal Artery in Vascular Ehlers-Danlos Syndrome.

    PubMed

    Pereira, Filipa; Cardoso, Teresa; Sá, Paula

    2015-01-01

    Ehlers-Danlos syndrome (EDS) is a rare heterogeneous group of connective tissue disorders. The vascular type (vEDS) is an autosomal dominant disorder caused by heterozygous mutations in the COL3A1 gene predisposing to premature arterial, intestinal, or uterine rupture. We report a case of a 38-year-old woman with a recent diagnosis of vEDS admitted in the Emergency Department with a suspicion of a pyelonephritis that evolved to a cardiopulmonary arrest. A fatal retroperitoneal hematoma related with a haemorrhagic dissection of the right renal artery was found after emergency surgery. This case highlights the need to be aware of the particular characteristics of vEDS, such as a severe vascular complication that can lead to a fatal outcome. PMID:26175915

  8. Total pleural covering technique for intractable pneumothorax in patient with Ehlers-Danlos syndrome.

    PubMed

    Kadota, Yoshihisa; Fukui, Eriko; Kitahara, Naoto; Okura, Eiji; Ohta, Mitsunori

    2016-07-01

    We report a patient with vascular-type Ehlers-Danlos syndrome (vEDS) who developed pneumothorax and was treated with a total pleural covering technique (TPC). A 24-year-old man developed repeat pneumothorax with intermittent hemo-sputum. Based on unusual radiological manifestations of lung lesions and physical findings, EDS was suspected as an underlying cause of the pneumothorax. Surgical treatment was performed using a mediastinal fat pad and TPC, and no relapse was seen up to 2 years after surgery. TPC is a less invasive surgical approach for selected patients with vEDS. Accurate underlying diagnosis of vEDS and systemic evaluation of vascular complications are necessary before planning surgery. PMID:25512090

  9. Spontaneous Dissection of the Renal Artery in Vascular Ehlers-Danlos Syndrome

    PubMed Central

    Pereira, Filipa; Cardoso, Teresa; Sá, Paula

    2015-01-01

    Ehlers-Danlos syndrome (EDS) is a rare heterogeneous group of connective tissue disorders. The vascular type (vEDS) is an autosomal dominant disorder caused by heterozygous mutations in the COL3A1 gene predisposing to premature arterial, intestinal, or uterine rupture. We report a case of a 38-year-old woman with a recent diagnosis of vEDS admitted in the Emergency Department with a suspicion of a pyelonephritis that evolved to a cardiopulmonary arrest. A fatal retroperitoneal hematoma related with a haemorrhagic dissection of the right renal artery was found after emergency surgery. This case highlights the need to be aware of the particular characteristics of vEDS, such as a severe vascular complication that can lead to a fatal outcome. PMID:26175915

  10. Hemolytic disease of the newborn

    MedlinePlus

    ... immature red blood cell (reticulocyte) count Bilirubin level Blood typing ... receiving extra fluids Light therapy (phototherapy) using ... Medicines to raise blood pressure if it drops too low In severe ...

  11. Paroxysmal cold hemoglobinuria (PCH)

    MedlinePlus

    ... condition. Bilirubin levels are high in blood and urine Complete blood count (CBC) shows anemia. Coombs test is negative. Donath-Landsteiner test is positive. Level of hemoglobin is increased during attacks. Lactate ...

  12. Jaundice

    MedlinePlus

    ... Autoimmune hepatitis Bile Biliary atresia Biliary stricture Bilirubin blood test Cholestasis Delta agent (Hepatitis D) Dubin-Johnson syndrome Gallstones Gilbert disease Hemolytic anemia Hepatitis A Hepatitis B Hepatitis C Malaria Newborn jaundice Pancreatic cancer Primary ...

  13. 76 FR 4918 - Drug-Induced Liver Injury: Are We Ready to Look?; Public Conference; Request for Comments

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-27

    ... for industry entitled ``Drug-Induced Liver Injury: Premarketing Clinical Evaluation'' (see 74 FR 38035... DILI by periodic tests of serum enzyme activities and bilirubin concentration elevations, and how...

  14. Treatment Options for Extrahepatic Bile Duct Cancer

    MedlinePlus

    ... checked to measure the amounts of bilirubin and alkaline phosphatase released into the blood by the liver. ... which a stent (a thin, flexible tube or metal tube) is placed in the bile duct to ...

  15. Biliary stricture

    MedlinePlus

    ... help reveal a problem with the biliary system . Alkaline phosphatase (ALP) is higher than normal. Bilirubin level ... the small intestine. In some cases, a tiny metal or plastic mesh tube ( stent ) is placed across ...

  16. Treatment Option Overview (Extrahepatic Bile Duct Cancer)

    MedlinePlus

    ... checked to measure the amounts of bilirubin and alkaline phosphatase released into the blood by the liver. ... which a stent (a thin, flexible tube or metal tube) is placed in the bile duct to ...

  17. Stages of Extrahepatic Bile Duct Cancer

    MedlinePlus

    ... checked to measure the amounts of bilirubin and alkaline phosphatase released into the blood by the liver. ... which a stent (a thin, flexible tube or metal tube) is placed in the bile duct to ...

  18. Immune hemolytic anemia

    MedlinePlus

    ... Absolute reticulocyte count Direct or indirect Coombs' test Hemoglobin in the urine LDH (level of this enzyme ... of tissue damage) Red blood cell count (RBC), hemoglobin, and hematocrit Serum bilirubin level Serum free hemoglobin ...

  19. Urine - abnormal color

    MedlinePlus

    ... can be caused by: Beets, blackberries, or certain food colorings Hemolytic anemia Injury to the kidneys or urinary tract Medicine Porphyria Urinary tract disorders that cause ... or drugs Bilirubin Medicines, including methylene blue Urinary ...

  20. Biliary Tract Disorders, Gallbladder Disorders, and Gallstone Pancreatitis

    MedlinePlus

    ... of bile from the liver (ALT, AST, alkaline phosphatase and bilirubin). Inflammation of the pancreas is best ... associated with an increase in the products and enzymes made by the liver, gallbladder and pancreas, which ...

  1. Urinalysis

    MedlinePlus

    ... or cloudy? Is it is pale, or dark yellow, or another color? MICROSCOPIC APPEARANCE The urine sample is examined under ... Normal urine varies in color from almost colorless to dark yellow. ... glucose, ketones, protein, and bilirubin are not detectable ...

  2. ALP (Alkaline Phosphatase) Test

    MedlinePlus

    ... known as: ALK PHOS; Alkp Formal name: Alkaline Phosphatase Related tests: AST ; ALT ; GGT ; Bilirubin ; Liver Panel ; Bone Markers ; Alkaline Phosphatase Isoenzymes; Bone Specific ALP All content on Lab ...

  3. AMA Test

    MedlinePlus

    ... Smooth muscle antibodies (SMA) Antinuclear antibodies (ANA) Alkaline phosphatase (ALP) IgM level Bilirubin Albumin Prothrombin time (PT) ... a liver panel (elevated liver enzymes), especially alkaline phosphatase (ALP) . An AMA or AMA-M2 test may ...

  4. PubMed Central

    Emond, Michel; Erlinger, Serge; Berthelot, Pierre; Benhamou, Jean-Pierre; Fauvert, Rene

    1966-01-01

    A case of novobiocin-induced jaundice is described in which the main feature was elevated unconjugated bilirubin in the serum. No evidence of hemolysis or hepato-cellular failure was demonstrated. The effect of novobiocin on serum bilirubin was studied by administering 2 g. of the drug daily in four divided oral doses for two days. An increase in serum unconjugated bilirubin was nearly always observed in the normal subjects and in patients with cirrhosis of the liver. This rise was particularly significant in three patients with hemolytic anemia and in two patients with Gilbert's disease. After an oral dose of 500 mg. the BSP clearance was decreased after one hour and it was close to normal after three hours. Since hemolysis is not responsible for this elevation of serum unconjugated bilirubin, the novobiocin-induced hyperbilirubinemia appears to be due to a direct effect of the drug upon the liver. PMID:4952370

  5. Application of optical diffusion theory to transcutaneous bilirubinometry

    NASA Astrophysics Data System (ADS)

    Spott, Thorsten; Svaasand, Lars O.; Anderson, R. E.; Schmedling, P. F.

    1998-01-01

    Neonatal hyperbilirubinemia affects more than half of the newborns and represents a potentially serious condition due to the toxicity of bilirubin to the central nervous system. A precise non-invasive technique for the monitoring of bilirubin concentration is desirable for the treatment of icteric babies. Transcutaneous bilirubinometry based on optical reflectance spectra is complicated by the superposition of the spectral absorption properties of melanin and haemoglobin with those of bilirubin. Diffusion theory forms a suitable model for the description of light propagation in tissue. In this treatment, an inverse diffusion approach is developed to measure bilirubin concentration in tissue by means of the reflectance spectrum. First results of its application to in vivo measurements are encouraging.

  6. Kernicterus

    MedlinePlus

    ... loss. The term "kernicterus" refers to the yellow staining caused by bilirubin. This is seen in parts ... diseases that involve the destruction of red blood cells (hemolysis). All newborns have a follow-up appointment ...

  7. Albumin - blood (serum) test

    MedlinePlus

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

  8. Role of extrahepatic UDP-glucuronosyltransferase 1A1: Advances in understanding breast milk-induced neonatal hyperbilirubinemia.

    PubMed

    Fujiwara, Ryoichi; Maruo, Yoshihiro; Chen, Shujuan; Tukey, Robert H

    2015-11-15

    Newborns commonly develop physiological hyperbilirubinemia (also known as jaundice). With increased bilirubin levels being observed in breast-fed infants, breast-feeding has been recognized as a contributing factor for the development of neonatal hyperbilirubinemia. Bilirubin undergoes selective metabolism by UDP-glucuronosyltransferase (UGT) 1A1 and becomes a water soluble glucuronide. Although several factors such as gestational age, dehydration and weight loss, and increased enterohepatic circulation have been associated with breast milk-induced jaundice (BMJ), deficiency in UGT1A1 expression is a known cause of BMJ. It is currently believed that unconjugated bilirubin is metabolized mainly in the liver. However, recent findings support the concept that extrahepatic tissues, such as small intestine and skin, contribute to bilirubin glucuronidation during the neonatal period. We will review the recent advances made towards understanding biological and molecular events impacting BMJ, especially regarding the role of extrahepatic UGT1A1 expression. PMID:26342858

  9. Infant Jaundice

    MedlinePlus

    ... treatment for jaundice get light therapy (also called phototherapy). During phototherapy, your baby is placed under special lights or ... baby’s body get rid of the excess bilirubin. Phototherapy usually lasts for 1 or 2 days. If ...

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

    PubMed

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

    1985-06-01

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

  11. Genetics Home Reference: Crigler-Najjar syndrome

    MedlinePlus

    ... from the body only after it undergoes a chemical reaction in the liver, which converts the toxic form ... the body. The bilirubin-UGT enzyme performs a chemical reaction called glucuronidation. During this reaction, the enzyme transfers ...

  12. Genetics Home Reference: Gilbert syndrome

    MedlinePlus

    ... from the body only after it undergoes a chemical reaction in the liver, which converts the toxic form ... the body. The bilirubin-UGT enzyme performs a chemical reaction called glucuronidation. During this reaction, the enzyme transfers ...

  13. Gallstones

    MedlinePlus

    ... of gallstones are cholesterol stones. 1 • Pigment stones, dark in color, are made of bilirubin. Who is ... To learn more about clinical trials, why they matter, and how to participate, visit the NIH Clinical ...

  14. Effect of rosiglitazone in sodium arsenite-induced experimental vascular endothelial dysfunction.

    PubMed

    Kaur, Tajpreet; Goel, Rajesh Kumar; Balakumar, Pitchai

    2010-04-01

    The present study has been designed to investigate the effect of rosiglitazone, a peroxisome proliferator activated receptor gamma agonist in sodium arsenite-induced vascular endothelial dysfunction (VED) in rats. The rats were administered sodium arsenite (1.5 mg/kg/day, i.p., 2 weeks) to induce VED. The development of VED was assessed by employing isolated aortic ring preparation and estimating serum nitrite/nitrate concentration. Further, the integrity of the aortic endothelium was assessed histologically using haematoxylin-eosin staining. Moreover, the oxidative stress was assessed by estimating serum thiobarbituric acid reactive substances, aortic reactive oxygen species and reduced form of glutathione. The administration of sodium arsenite produced VED by impairing acetylcholine-induced endothelium dependent relaxation, diminishing the integrity of vascular endothelium and decreasing the serum nitrite/nitrate concentration. In addition, sodium arsenite was noted to produce oxidative stress as it increased serum thiobarbituric acid reactive substances and aortic reactive oxygen species and consequently decreased glutathione. Treatment with rosiglitazone (3 mg/kg/day, p.o., 2 weeks and 5 mg/kg/day, p.o., 2 weeks) significantly prevented sodium arsenite-induced VED by enhancing acetylcholine-induced endothelium dependent relaxation, improving the integrity of vascular endothelium, increasing the nitrite/nitrate concentration and decreasing the oxidative stress. However, the vascular protective effect of rosiglitazone was markedly abolished by co-administration of nitric oxide synthase inhibitor, N-Omega-Nitro-L-Arginine Methyl Ester (L-NAME) (25 mg/kg/day, i.p., 2 weeks). Thus, it may be concluded that rosiglitazone reduces oxidative stress, activates eNOS and enhances the generation of nitric oxide to prevent sodium arsenite-induced VED in rats. PMID:20422371

  15. Benfotiamine attenuates nicotine and uric acid-induced vascular endothelial dysfunction in the rat.

    PubMed

    Balakumar, Pitchai; Sharma, Ramica; Singh, Manjeet

    2008-01-01

    The study has been designed to investigate the effect of benfotiamine, a thiamine derivative, in nicotine and uric acid-induced vascular endothelial dysfunction (VED) in rats. Nicotine (2 mg kg(-1)day(-1), i.p., 4 weeks) and uric acid (150 mg kg(-1)day(-1), i.p., 3 weeks) were administered to produce VED in rats. The development of VED was assessed by employing isolated aortic ring preparation and estimating serum and aortic concentration of nitrite/nitrate. Further, the integrity of vascular endothelium was assessed using the scanning electron microscopy (SEM) of thoracic aorta. Moreover, the oxidative stress was assessed by estimating serum thiobarbituric acid reactive substances (TBARS) and aortic superoxide anion generation. The administration of nicotine and uric acid produced VED by impairing the integrity of vascular endothelium and subsequently decreasing serum and aortic concentration of nitrite/nitrate and attenuating acetylcholine-induced endothelium dependent relaxation. Further, nicotine and uric acid produced oxidative stress, which was assessed in terms of increase in serum TBARS and aortic superoxide generation. However, treatment with benfotiamine (70 mg kg(-1)day(-1), p.o.) or atorvastatin (30 mg kg(-1)day(-1) p.o., a standard agent) markedly prevented nicotine and uric acid-induced VED and oxidative stress by improving the integrity of vascular endothelium, increasing the concentration of serum and aortic nitrite/nitrate, enhancing the acetylcholine-induced endothelium dependent relaxation and decreasing serum TBARS and aortic superoxide anion generation. Thus, it may be concluded that benfotiamine reduces the oxidative stress and consequently improves the integrity of vascular endothelium and enhances the generation of nitric oxide to prevent nicotine and uric acid-induced experimental VED. PMID:18951979

  16. Inheritance of type 2 Crigler-Najjar hyperbilirubinaemia

    PubMed Central

    Hunter, J. O.; Thompson, R. P. H.; Dunn, P. M.; Williams, Roger

    1973-01-01

    The families of three patients with Crigler-Najjar hyperbilirubinaemia, type 2, whose plasma bilirubin levels had responded to phenobarbitone treatment, were investigated. All the parents and several relatives had mildly raised bilirubin levels. It is suggested that this condition may be an example of genetic heterogeneity and that the propositi had inherited two different abnormal genes. The separation of the Gilbert and type 2 Crigler-Najjar syndromes is at present arbitrary. PMID:4692254

  17. [Transitory hyperbilirubinemia and oxytocin infusion].

    PubMed

    Quoss, I

    1978-01-01

    Serum bilirubin levels at 5th day of life was compared between 100 mature newborns with oxytocin infusion to the mother during labour and 100 mature newborns without oxytocin. Newborns, whose mothers received more than 5 IU oxytocin had significant higher bilirubin values than the controll group without oxytocin and the cases with oxytocin administration under 5 U. Hyperbilirubinaemie was also present in babies after vacuum extraction and oxytocin infusion. PMID:645287

  18. A rapid and sensitive method for HPLC cholesterol determination in bile.

    PubMed

    Bocos, C; Castro, M; Orozco, E; Contreras, J A; Herrera, E

    1992-09-01

    A relatively little time consuming simple method based on the treatment of bile with cholesterol oxidase and subsequent high performance liquid chromatography measurement of the 3-ketocholesterol produced in order to determine the level of the cholesterol concentration is described. The method avoids bilirubin interferences, has high reproducibility and recovery assays give 100% values. It is highly sensitive and suitable for use in the determination of cholesterol concentrations in bile and other bilirubin containing biological fluids. PMID:1301638

  19. Conjugation Inhibitors and Early Neonatal Hyperbilirubinaemia

    PubMed Central

    Cole, A. P.; Hargreaves, T.

    1972-01-01

    Milk and serum were obtained from 50 mothers on the 6th day post partum and examined for inhibitory activity against bilirubin conjugation in rat liver slices. Neonatal serum bilirubin levels were also analysed at this time. There was no relation between the amount of inhibitory substance in breast milk or serum and the degree of neonatal hyperbilirubinaemia. It was observed that inhibitory activity increased in frozen breast milk but not in frozen autoclaved breast milk. PMID:5034671

  20. Vitamin E deficiency ataxia associated with adenoma.

    PubMed

    Benomar, A; Yahyaoui, M; Marzouki, N; Birouk, N; Bouslam, N; Belaidi, H; Amarti, A; Ouazzani, R; Chkili, T

    1999-01-01

    Vitamin E is one of the most important lipid-soluble antioxidant nutrient. Severe vitamin E deficiency (VED) can have a profound effect on the central nervous system. VED causes ataxia and peripheral neuropathy that resembles Friedreich's ataxia. We report here a patient presenting this syndrome, but also a prolactin and FSH adenoma. Both the neurological syndromes and the adenoma regressed after treatment with alpha-tocopherol. Although, the presence of the prolactinoma in this patient may not be related to his vitamin E deficiency, alpha-tocopherol treatment seems to be beneficial and might usefully be tested in patients with hypophyseal secreting other forms of adenoma. PMID:10064178

  1. Cervical artery dissections and type A aortic dissection in a family with a novel missense COL3A1 mutation of vascular type Ehlers-Danlos syndrome.

    PubMed

    Makrygiannis, Georgios; Loeys, Bart; Defraigne, Jean-Olivier; Sakalihasan, Natzi

    2015-11-01

    Cervical artery dissection (CeAD) is a rare condition. One of the causes is the vascular type of Ehlers-Danlos syndrome (vEDS). A novel missense mutation in COL3A1 was found in a young patient with CeAD as the single manifestation of vEDS. This is a heterozygous c.953G > A mutation in exon 14, disrupting the normal Gly-X-Y repeats of type III procollagen, by converting glycine to aspartic acid. PMID:26497932

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

    PubMed

    Ohkawa, T; Norikura, R; Yoshikawa, T

    2003-04-10

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

  3. A Culture-Based Model for Strategic Implementation of Virtual Education Delivery

    ERIC Educational Resources Information Center

    Burn, Janice; Thongprasert, Nalinee

    2005-01-01

    This study was designed to examine the critical success factors for implementing Virtual Education Delivery (VED) in Thailand, and to identify ways to facilitate such adoption and lead to effective outcomes. The study incorporated an analysis of three specific factors related to Thai culture: high power distance "Bhun Khun", uncertainty…

  4. Types of Empathy and Adolescent Sexual Offenders

    ERIC Educational Resources Information Center

    Varker, Tracey; Devilly, Grant J.

    2007-01-01

    The purpose of this study was to examine general empathy, general victim empathy and own victim empathy in adolescent sexual offenders. Sixteen adolescent sexual offenders completed the Interpersonal Reactivity Index (IRI), the Personal Reaction Inventory, a "general sexual abuse victim" form of the Victim Empathy Distortions Scale (VEDS) and an…

  5. Hearings on Reauthorization of the Vocational Education Act of 1963. Part 10: Vocational Education Data System. Hearing before the Subcommittee on Elementary, Secondary, and Vocational Education of the Committee on Education and Labor. House of Representatives. Ninety-Seventh Congress. First Session (December 10, 1981).

    ERIC Educational Resources Information Center

    Congress of the U.S., Washington, DC. House Committee on Education and Labor.

    This is a report of a hearing on December 10, 1981, before the Subcommittee on Elementary, Secondary, and Vocational Education of the Committee on Education and Labor, House of Representatives, regarding reauthorization of the Vocational Education Act of 1963. It focuses on the vocational education data system known as VEDS. Testimony includes…

  6. Community College Journal for Research and Planning.

    ERIC Educational Resources Information Center

    Carter, Edith H., Ed.

    1981-01-01

    This journal, designed as a forum for the exchange of ideas among research and planning professionals, offers articles of research studies and practices. After Timothy Lightfield highlights upcoming professional association events, Janice S. Ancarrow's article, "The National Vocational Education Data Reporting and Accounting System (VEDS): Its…

  7. Performance of an array of vertical dipoles over an inhomogeneous ground system

    SciTech Connect

    King, R.J.; Mathur, N.C.

    1983-03-01

    The elevation radiation patterns of a stacked array of vertical electric dipoles (VEDs) over several different azimuthally symmetric inhomogeneous ground systems are studied using an integral formulation. As the ground influences the pattern of each VED differently, there is no known optimum array excitation which can be used to achieve desired beam shaping and steering. Patterns in an array of 21 VEDs spaced 0.1 lambda apart are computed and compared to HF (10 MHz) for three excitation functions: (a) conventional linear spacial phasing, (b) phasing according to the complex conjugate of the field produced by each VED in the direction of steering, and (c) spacially sinusoidal excitation with constant phasing. Results are given for grounds consisting of homogeneous earth, a perfectly conducting ground plane, a perfectly conducting disk on homogeneous earth and 2 lambda long radial wire ground systems on well- and poorly-conducting earth. It is found that the radiation pattern cannot be steered below about 9/sup 0/ in elevation for any of the excitation functions or the ground systems used. For low-angle steering conjugate excitation produces a slightly narrower beam with smaller sidelobes. Highly conducting grounds tend to permit steering to slightly higher elevations with narrower beams.

  8. Vocational Education. Report by the Secretary of Education to the Congress, 1981.

    ERIC Educational Resources Information Center

    Office of Vocational and Adult Education (ED), Washington, DC.

    This annual report provides an overview of the status of vocational education during school year 1980-81. It includes final data for school year 1979-80 obtained through the Vocational Education Data System (VEDS), the national vocational education reporting and accounting system. Part 1 of the report describes the status of vocational education…

  9. Exploring the Meaningful Learning of Students in Second Life

    ERIC Educational Resources Information Center

    Keskitalo, Tuulikki; Pyykko, Elli; Ruokamo, Heli

    2011-01-01

    This study reports a case study in which a pedagogical model, namely the Global Virtual Education (GloVEd) model, which is based on the teaching-studying-learning process (TSL process) and the characteristics of meaningful learning, is developed and used to evaluate students' meaningful learning experiences during the Global Virtual Collaboration…

  10. Embolization of Life-Threatening Arterial Rupture in Patients with Vascular Ehlers–Danlos Syndrome

    SciTech Connect

    Okada, Takuya; Frank, Michael; Pellerin, Olivier Primio, Massimiliano Di Angelopoulos, Georgios; Boughenou, Marie-Fazia; Pagny, Jean-Yves; Messas, Emmanuel; Sapoval, Marc

    2013-05-09

    PurposeTo evaluate the safety and efficacy of transarterial embolization of life-threatening arterial rupture in patients with vascular Ehlers–Danlos syndrome (vEDS) in a single tertiary referral center.MethodsWe retrospectively analyzed transarterial embolization for vEDS performed at our institution from 2000 to 2012. The indication of embolization was spontaneous arterial rupture or pseudoaneurysm with acute bleeding. All interventions used a percutaneous approach through a 5F or less introducer sheath. Embolic agents were microcoils and glue in 3 procedures, glue alone in 2, and microcoils alone in 2.ResultsFive consecutive vEDS patients were treated by 7 embolization procedures (4 women, mean age 29.8 years). All procedures were successfully performed. Two patients required a second procedure for newly arterial lesions at a different site from the first procedure. Four of the five patients were still alive after a mean follow-up of 19.4 (range 1–74.7) months. One patient died of multiple organ failure 2 days after procedure. Minor procedural complications were observed in 3 procedures (43 %), all directly managed during the same session. Remote arterial lesions occurred after 3 procedures (43 %); one underwent a second embolization, and the other 2 were observed conservatively. Puncture site complication was observed in only one procedure (14 %).ConclusionEmbolization for vEDS is a safe and effective method to manage life-threatening arterial rupture.

  11. Effect of poly (2-methoxyethyl acrylate)-coated oxygenators on haemolysis.

    PubMed

    Kocakulak, M; Ozgürtaş, T; Ayhan, H

    2006-01-01

    Blood contact with artificial device surfaces and mechanical trauma are two major factors for haemolysis. Poly(2-methoxyethyl acrylate) (PMEA) is an amphiphilic polymer with a polyethylene chain that is hydrophobic and a mildly hydrophilic tail. PMEA coating has showed positive effects on protein adsorption, platelet loss, platelet aggregation and post-operative bleeding in previous studies. In this study, effects of poly(2-metoxyethyl acrylate) (PMEA)-coated oxygenators on haemolysis was investigated. PMEA-coated (SX18-Capiox) oxygenators were used. Desorbed erythrocyte, free haemoglobin indirect bilirubin and total bilirubin quantities from fibre samples of oxygenators were studied. Erythrocyte, total bilirubin and direct bilirubin values were measured from blood aliquots taken in five different times during cardiopulmonary by-pass (CPB); baseline (T1), during CPB (T2), at the end of CPB (T3), after protamine injection (T4) and in intensive care (T5). In both coated and non-coated oxygenators haemolysis rate was in clinically acceptable safety range. Average desorbed free haemoglobin was 6663 mg/dl from coated and 29.405 mg/dl from non-coated fibres. Average desorbed total bilirubin was 0.0068 mg/dl from coated and 0.023 mg/dl from noncoated fibres. We observed less haemolysis, as reflected by lower desorbed free haemoglobin and indirect bilirubin from coated oxygenators and less decrease in blood erythrocyte number. Blood bilirubin concentration was low in the coated group when compared to the control group. This study describes the relationship between PMEA coating and haemolysis at the blood contacting surface. PMEA coating reduces red blood cell damage during extracorporeal circulation. PMID:16768295

  12. Pancreatic islet regeneration and some liver biochemical parameters of leaf extracts of Vitex doniana in normal and streptozotocin-induced diabetic albino rats

    PubMed Central

    Oche, Okpe; Sani, Ibrahim; Chilaka, Njoku Godwin; Samuel, Ndidi Uche; Samuel, Atabo

    2014-01-01

    Objective To test two water soluble extracts (aqueous and ethanolic) obtained from the leaves of Vitex doniana in normal and streptozotocin-induced diabetic rats for their effects on pancreatic endocrine tissues and serum marker enzymes for a period of 21 d. Methods A total of 55 rats divided into 11 groups of 5 rats each were assigned into diabetic and non-diabetic groups and followed by a daily administration of ethanolic and aqueous extracts for 21 d. Group 1 was the normal control while group 7 was treated with standard drug. Results The histopathological studies of the diabetic rats indicated increase in the volume density of islets, percent of β-cells and size of islet in the groups that received the plant extracts, which suggested regeneration of β-cells along with β-cells repairs, as compared with the non-treated diabetic control which showed complete degeneration of the islet cells. There was significant reduction (P<0.05) in the serum activities of marker enzymes, alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase in diabetes treated rats, whereas an insignificant increase (P>0.01) in the serum activities of marker enzymes was observed for non-diabetic treated rats. Results of total bilirubin, direct bilirubin and unconjugated bilirubin showed that diabetic control group was significantly higher (P<0.05) in total bilirubin and unconjugated bilirubin compared with treated groups while non-diabetic treated groups showed no significant increase (P>0.01) in total bilirubin and direct bilirubin compared with the normal control. Conclusion This herbal therapy appears to bring about repair/regeneration of the endocrine pancreas and hepatic cells protection in the diabetic rat. PMID:25182283

  13. Fenofibrate attenuates nicotine-induced vascular endothelial dysfunction in the rat.

    PubMed

    Chakkarwar, Vishal Arvind

    2011-01-01

    The study has been designed to investigate the effect of fenofibrate on nicotine-induced vascular endothelial dysfunction (VED) in rats. Nicotine (2 mg/kg/day, i.p., 4 weeks) was administered to produce VED in rats. The development of VED was assessed by employing isolated aortic ring preparation and estimating serum and aortic concentration of nitrite/nitrate. Further, the integrity of vascular endothelium was assessed using the scanning electron microscopy of thoracic aorta. The expression of mRNA for p22phox and eNOS was assessed by using reverse transcriptase-polymerase chain reaction. Serum thiobarbituric acid reactive substances concentration (TBARS) and aortic superoxide anion concentration were estimated to assess oxidative stress. Moreover, the serum lipid profile was assessed by estimating serum cholesterol, triglycerides and high density lipoprotein. The administration of nicotine induces VED by increased oxidative stress, altered lipid profile and impaired the integrity of vascular endothelium as assessed in terms of decrease in expression of mRNA for endothelial nitric oxide synthase (eNOS), impairing the integrity of vascular endothelium and subsequently decreasing serum and aortic nitrite/nitrate and attenuating acetylcholine-induced endothelium dependent relaxation. Further, nicotine produced oxidative stress, assessed in terms of increase in serum TBARS and aortic superoxide anion generation and increase in expression of mRNA for p22phox. Nicotine altered the lipid profile by increasing the serum cholesterol, triglycerides and decreasing the high density lipoprotein. However, treatment with fenofibrate (32 mg/kg, p.o.) markedly prevented nicotine-induced VED by decreasing oxidative stress and improving integrity of vascular endothelium, normalising the altered lipid profile, increasing the concentration of serum and aortic nitrite/nitrate, enhancing the acetylcholine-induced endothelium dependent relaxation and decreasing serum TBARS and aortic

  14. Electrical activity of corpus cavernosum in vasculogenic and non-vasculogenic erectile dysfunction.

    PubMed

    Atahan, O; Kayigil, O; Metin, A

    1997-12-01

    We aimed to compare the electrical activity of corpus cavernosum before and after intracavernous papaverine injection and to determine the blood lipid profile in vascular and non-vascular erectile dysfunction, and also to assess whether vascular pathology and abnormal blood lipid levels impair cavernosal smooth-muscle relaxation. We determined total cholesterol (TC), triglyceride (TG) and high-density lipoprotein (HDL) levels in peripheral and cavernosal blood in 39 patients with erectile dysfunction. Electromyography of the corpus cavernosum was performed before and after an intracavernous injection with 60 mg of papaverine in all patients. Thirty-nine impotent patients have been divided into two groups: vasculogenic erectile dysfunction (VED) and non-vasculogenic erectile dysfunction (NVED), according to colour Doppler ultrasonic flowmetry, dynamic infusion cavernosometry and the pressure difference between the brachial arterial systolic pressure and cavernosal arterial systolic pressure measurements. Biochemical values and amplitude changes were compared in both groups. The TC level was higher in both peripheral and cavernosal samples of the VED group than in the NVED group (p = 0.000), with no differences between peripheral and cavernosal blood levels within the same groups (p > 0.05). There were no significant changes in TG and HDL levels in any of the groups (p > 0.05). The mean amplitude differences before and after papaverine injection (delta A) were found to be 2.05 +/- 0.78 microV in the VED group and 4.68 +/- 2.53 microV in the NVED group, showing that the relaxation response to papaverine was more significant in the NVED than in the VED group (p = 0.003). The moderate decreases in the amplitude of electrical activity of corpus cavernosum and the higher TC levels found in the VED group can be accepted as the parameters of impairment in the relaxation of corpus cavernosum, showing the role of hypercholesterolaemia and vascular pathologies in erectile

  15. Involvement of Rho-kinase in experimental vascular endothelial dysfunction.

    PubMed

    Shah, Dhvanit I; Singh, Manjeet

    2006-02-01

    The present study has been designed to investigate the effect of fasudil (Rho-kinase inhibitor) in diabetes mellitus (DM) and hyperhomocyteinemia (HHcy) induced vascular endothelial dysfunction (VED). Streptozotocin (55 mg kg(-1), i.v., once only) and methionine (1.7% w/w, p.o., daily for 4 weeks) were administered to rats to produce DM (serum glucose >140 mg dl(-1)) and HHcy (serum homocysteine >10 microM) respectively. VED was assessed using isolated aortic ring, electron microscopy of thoracic aorta, and serum concentration of nitrite/nitrate. Serum thiobarbituric acid reactive substances (TBARS) concentration was estimated to assess oxidative stress. Atorvastatin has been employed in the present study as standard agent to improve vascular endothelial dysfunction. Fasudil (15 mg kg(-1) and 30 mg kg(-1), p.o., daily) and atorvastatin (30 mg kg(-1), p.o., daily) treatments significantly attenuated increase in serum glucose and homocysteine but their concentrations remained markedly higher than sham control value. Fasudil and atorvastatin treatments markedly prevented DM and HHcy-induced (i) attenuation of acetylcholine induced endothelium-dependent relaxation, (ii) impairment of vascular endothelial lining, (iii) decrease in serum nitrite/nitrate concentration, and (iv) increase in serum TBARS. It may be concluded that fasudil prevented DM and HHcy-induced VED partially by decreasing serum glucose and homocysteine concentration due to inhibition of Rho-kinase. Moreover, inhibition of Rho-kinase by fasudil and consequent prevention of oxidative stress may have directly improved VED in diabetic and hyperhomocysteinemic rats. The Rho-kinase appears to be a pivotal target site involved in DM and HHcy-induced VED. PMID:16444602

  16. Is early measles vaccination better than later measles vaccination?

    PubMed

    Aaby, Peter; Martins, Cesário L; Ravn, Henrik; Rodrigues, Amabelia; Whittle, Hilton C; Benn, Christine S

    2015-01-01

    WHO recommends delaying measles vaccination (MV) until maternal antibody has waned. However, early MV may improve child survival by reducing mortality from conditions other than measles infection. We tested whether early MV improves child survival compared with later MV. We found 43 studies comparing measles-vaccinated and measles-unvaccinated children; however, only 16 studies had specific information that MV had been provided at 4-13 months of age, many before 9 months of age. In the 10 best studies (4 randomized trials and 6 observational studies) control children did not receive MV during follow-up. In eight of these studies the vaccine efficacy against death (VED) was 60% or more. In four studies with information on MV provided both before and after 12 months of age, the all-cause mortality reduction was significantly larger for children vaccinated in infancy (VED=74%; 95% CI 51-86%) than for children vaccinated after 12 months of age (VED=29%; CI 8-46%). Prevention of measles explained little of the reduction in mortality. In five studies with information on measles infection, VED was 67% (51-78%) and when measles deaths were excluded, VED was only reduced to 65% (47-77%). One natural experiment compared MV at 4-8 months versus MV at 9-11 months of age and found significantly lower all-cause mortality with early vaccination, the difference being 39% (8-60%). Child mortality may be reduced if MV is given earlier than currently recommended by international organizations. PMID:25573106

  17. Interleukin-27 inhibits vaccine-enhanced pulmonary disease following respiratory syncytial virus infection by regulating cellular memory responses.

    PubMed

    Zeng, Ruihong; Zhang, Huixian; Hai, Yan; Cui, Yuxiu; Wei, Lin; Li, Na; Liu, Jianxun; Li, Caixia; Liu, Ying

    2012-04-01

    Respiratory syncytial virus (RSV) is the most important cause of lower respiratory tract disease in young children. In the 1960s, infants vaccinated with formalin-inactivated RSV developed a more severe disease characterized by excessive inflammatory immunopathology in lungs upon natural RSV infection. The fear of causing the vaccine-enhanced disease (VED) is an important obstacle for development of safe and effective RSV vaccines. The recombinant vaccine candidate G1F/M2 immunization also led to VED. It has been proved that cellular memory induced by RSV vaccines contributed to VED. Interleukin-27 (IL-27) and IL-23 regulate Th1, Th17, and/or Th2 cellular immune responses. In this study, mice coimmunized with pcDNA3-IL-27 and G1F/M2 were fully protected and, importantly, did not develop vaccine-enhanced inflammatory responses and immunopathology in lungs after RSV challenge, which was correlated with moderate Th1-, suppressed Th2-, and Th17-like memory responses activated by RSV. In contrast, G1F/M2- or pcDNA3-IL-23+G1F/M2-immunized mice, in which robust Th2- and Th17-like memory responses were induced, developed enhanced pulmonary inflammation and severe immunopathology. Mice coimmunized with G1F/M2 and the two cytokine plasmids exhibited mild inflammatory responses as well as remarkable Th1-, suppressed Th2-, and Th17-like memory responses. These results suggested that Th1-, Th2-, and Th17-like memory responses and, in particular, excessive Th2- and Th17-like memory responses were closely associated with VED; IL-27 may inhibit VED following respiratory syncytial virus infection by regulating cellular memory responses. PMID:22301139

  18. Preparation and properties of crystalline biliverdin IX alpha. Simple methods for preparing isomerically homogeneous biliverdin and [14C[biliverdin by using 2,3-dichloro-5,6-dicyanobenzoquinone.

    PubMed Central

    McDonagh, A F; Palma, L A

    1980-01-01

    Amorphous isomerically pure biliverdin IX alpha is readily prepared in more than 70% yield by dehydrogenation of bilirubin with 2,3-dichloro-5,6-dicyanobenzoquinone in dimethyl sulphoxide under carefully controlled conditions. Crystalline biliverdin IX alpha and amorphous [14C]biliverdin can be obtained similarly in more than 40+ yield. The pure crystalline pigment was characterized by elemental analysis, methylation, chemical and enzymic reduction to bilirubin, i.r.- and u.v.-visible-absorption spectroscopy, n.m.r. spectroscopy and field-desorption mass spectrometry, and its solubility was determined. Under certain conditions, dehydrogenation, gave biliverdin contaminated with III alpha and XIII alpha isomers as a result of disproporationation of bilirubin. Formation of non-IX alpha isomers depends on the concentrations of the reagents and the order in which they are mixed, and occurs under neutral anaerobic conditions. Free-radical reactions probably are responsible, suggesting that the first step in the deydrogenation of bilirubin with 2,3-dichloro-5,6-dicyanobenzoquinone in dimethyl sulphoxide is formation of a bilirubin cation radical, rather than hydride ion abstraction. Images Fig. 1. Fig. 2. PMID:7458909

  19. Monte Carlo Simulation of Visible Light Diffuse Reflection in Neonatal Skin

    NASA Astrophysics Data System (ADS)

    Atencio, J. A. Delgado; Rodríguez, E. E.; Rodríguez, A. Cornejo; Rivas-Silva, J. F.

    2008-04-01

    Neonatal jaundice is a medical condition that happens commonly in newborns as result of desbalance between the production and the elimination of the bilirubin. Around 50% of newborns in term and something more of 60% of the near-term becomes jaundiced in the first week of life. This excess of bilirubin in the blood is exhibited in the skin, the sclera of the eyes and the mucous of mouth like a characteristic yellow coloration. In this work we make several numerical simulations of the spectral diffuse reflection for the skin of newborns that present different values of the biological parameters (bilirubin content, grade of pigmentation and content of blood) that characterize it. These simulations will allow us to evaluate the influence of these parameters on the experimental determination of bilirubin by noninvasive optical methods. The simulations are made in the spectral range of 400-700 nm using the Monte Carlo code MCML and two programs developed in LabVIEW by the authors. We simulated the diffuse reflection spectrum of neonatal skin for concentrations of bilirubin in skin that covers an ample range: from physiological to harmful numbers. We considered the influence of factors such as grade of pigmentation and content of blood.

  20. Effect of Bile Pigments on the Compromised Gut Barrier Function in a Rat Model of Bile Duct Ligation

    PubMed Central

    Liu, Yuanli; Qu, Yilin; Shi, Guojing; Yang, Xinguang; Qin, Xiaofa; Wang, Xiuhong

    2014-01-01

    Background Studies have shown that the absence of bile in the gut lumen, either by bile duct ligation or bile diversion, induces mucosal injury. However, the mechanism remains elusive. In this study, the role of bile pigments in gut barrier function was investigated in a rat model of bile duct ligation. Methods Male Sprague Dawley (SD) rats were used in this study. After ligation of bile duct, the animals were administrated with free bilirubin, bilirubin ditaurate, or biliverdin by intragastric gavage. 1, 2, or 3 days later, the animals were sacrificed and the damage of mucosa was assessed by histological staining as well as biochemical parameters such as changes of diamine oxidase (DAO) and D-lactate (D-Lac) in the blood. Trypsin and chymotrypsin of the gut were also measured to determine how these digestive proteases may relate to the observed effects of bile pigments. Results Bile duct ligation (BDL) caused significant increases in gut trypsin and chymotrypsin along with damage of the mucosa as demonstrated by the histological findings under microscope, the reduced expression of tight junction molecules like occludin, and significant changes in DAO and D-lac in the blood. Free bilirubin but not bilirubin ditaurate or biliverdin showed significant inhibitions on trypsin and chymotrypsin as well as alleviated changes of histological and biochemical parameters related to gut barrier disruption. Conclusion Bile may protect the gut from damage through inhibiting digestive proteases like trypsin and chymotrypsin by free bilirubin. PMID:24892651

  1. Possible Ibuprofen-Induced Kernicterus in a Near-Term Infant with Moderate Hyperbilirubinemia.

    PubMed Central

    Gal, Peter; Ransom, J Laurence; Davis, Sherri A

    2006-01-01

    A 36-week gestation newborn was admitted to the neonatal intensive care unit for treatment of primary pulmonary hypertension and possible sepsis. The infant developed hyperbilirubinemia on day 4 of life and peaked on day 5 at a total serum bilirubin of 19 mg/dL. Phototherapy was started on day 4 and continued for 5 days. On day 8 of life, ibuprofen was started for fever; a concurrent total serum bilirubin was 15.7 mg/dL. The subsequent hospital course was uneventful, and discharge occurred on day 22 of life. Because the patient failed a hearing screen at discharge, he was referred for a diagnostic audiology workup. He subsequently failed formal audiometric testing on two occasions one week apart, and was given a diagnosis of auditory dys-synchrony and/or auditory neuropathy, consistent with kernicterus. At 5½ months of age, he was reported to be hypotonic and to have frequent arching movements. Since the total serum bilirubin did not exceed 19 mg/dL, concern was raised that ibuprofen may have caused displacement of bilirubin from its albumin binding site, resulting in kernicterus due to excessive unbound bilirubin concentrations. Ibuprofen should be administered with caution in preterm infants at risk for kernicterus. PMID:23115541

  2. Screening for neonatal hyperbilirubinaemia and ABO alloimmunization at the time of testing for phenylketonuria and congenital hypothyreosis.

    PubMed

    Meberg, A; Johansen, K B

    1998-12-01

    In a population-based study including 2463 infants, serum bilirubin measurements were added to the neonatal screening programme for phenylketonuria and congenital hypothyreosis. This screening programme detected 11/17 (65%) of infants with serum bilirubin levels >350 micromol 1(-1), of whom 7 (3 per 1000) were readmitted from home (6 treated with phototherapy). A total of 139 infants (5.6%) received phototherapy. Maternal blood type O occurred significantly more often in term infants treated (30/54; 55.6%) compared with preterm infants treated (32/85; 37.6%) and with blood type O occurrence in the total population of mothers (906/2426; 37.3%) (p < 0.05). The blood type constellations mother O/infant A or B showed a sensitivity of 64%, specificity 65%, positive predictive value 12% and a negative predictive value of 96% for the requirement of phototherapy for the whole material. Exchange transfusion was not required in any of the infants. No infant developed bilirubin encephalopathy (kemicterus). Adding bilirubin to a neonatal screening programme detects some cases with unexpectedly high bilirubin levels in need of intervention. Routine ABO blood typing of pregnant women, ABO cord blood typing and Coombs' test in infants of mothers with blood type O cannot be recommended because of low positive predictive value for the requirement of intervention (phototherapy) by these tests. PMID:9894828

  3. Anti-hyperbilirubinemic and wound healing activity of aqueous extract of Calotropis procera leaves in Wistar rats

    PubMed Central

    Patil, Rupali Arun; Makwana, Aakash B.

    2015-01-01

    Aims: The aim of this study was to evaluate the bilirubin lowering and wound healing property of aqueous extract of Calotropis procera (AECP) leaves in Wistar rats. Materials and Methods: Albino Wistar rats of either sex were used for the study. Bilirubin lowering property of C. procera leaves was evaluated using phenylhydrazine and paracetamol as inducing agents followed by measuring the concentration of serum total bilirubin in hyperbilirubinemic rats. Wound healing property was evaluated using incision and excision models by measuring tensile breaking strength, percentage wound contractions, and epithelization days, respectively. Statistical Analysis: Statistical comparison between groups in each experiment was done with one-way analysis of variance followed by Dunnett's test. Results: AECP showed a significant (P < 0.05) decrease in concentrations of serum total bilirubin in hyperbilirubinemic rats as well as significant (P < 0.05) increase in breaking strength and percentage wound contractions with decreased epithelization period when compared to control groups. Conclusions: AECP showed significant bilirubin lowering and wound healing property in Wistar rats. PMID:26288472

  4. Effect of Vimala Massage on Physiological Jaundice in Infants: A Randomized Controlled Trial

    PubMed Central

    Seyyedrasooli, Alehe; Valizadeh, Leila; Hosseini, Mohammad Bager; Asgari Jafarabadi, Mohammad; Mohammadzad, Masoome

    2014-01-01

    Introduction: Considering the prevalence of Jaundice in newborn infants and the risk of developing acute Bilirubin encephalopathy, in early weeks after birth. the importance of Infancy, as well as positive effects of giving massage on physical and behavioral growth and evolution of infants, the current study has been aimed to investigate the effects of Vimala massage on neonatal physiological Jaundice. Methods: This is a single blind clinical trial study, 43 healthy term infants, with 1st day Bilirubin levels of less than 5mg/dl, carried out in Tabriz Al-Zahra hospital. Newborns were selected through convenience sampling and then randomly assigned to intervention and control groups. Control group received routine care, while newborns of intervention group received four days of Vimala massage starting from the first day of their birth. Main variables of study include transcutaneous Bilirubin and frequency of defecation. Collected data were analyzed by SPSS Ver.13 through Chi-square and Mann-Whitney tests. Results: There were no statistical significant differences between two groups for skin bilirubin, however the number of defecations in the intervention group exceeded than of control group, and was statistically significant. Conclusion: The Results show that Vimala massage within four days has no effect on increasing process of bilirubin, yet can affect the incidence rate of physiological Jaundice and care of infants by increasing defecation frequency. PMID:25276760

  5. [How reliable are assays with the ictometer? Comparative studies with direct measurement of billirubin and a diazo technique (author's transl)].

    PubMed

    Schulz, D; Gerstheimer, A

    1976-01-01

    Comparison of measurements of a diazo technique with those of a direct assessment of bilirubin with the photo-ictometer type II (Hirtz & Co., Cologne). Comparative analysis of total bilirubin-concentration in 172 non-hemolytic sera of neonates and in dilution series with and without contamination by hemoglobin and/or lipid-suspension gave the following results and conclusions drawn from them: 1. In non-contaminated sera the relation between the two techniques is linear, well correlated, parallel and with little divergence. 2. In contrast to the ictometer the diazo technique used underrates the bilirubin content in hemolytic sera. 3. In contrast to the diazo technique the ictometer underrates the bilirubin content in strongly turbid sera. 4. The precision of the ictometer is superior in series and from day to day to the already good precision of the diazo technique. 5. The standard built- in after calibration has to be checked daily and adjusted during the first working hour of the ictometer on several occasions. 6. In order to aboid major systematic faults each apparatus should be compared with a safely calibrated technique. 7. The very simple and rapidly serviced apparatus is suitable for the assay of total bilirubin in sera of the newborn. For older neonates and after exchanges transfusions the results should not be trusted. PMID:943668

  6. Rv2074 is a novel F420 H2 -dependent biliverdin reductase in Mycobacterium tuberculosis.

    PubMed

    Ahmed, F Hafna; Mohamed, A Elaaf; Carr, Paul D; Lee, Brendon M; Condic-Jurkic, Karmen; O'Mara, Megan L; Jackson, Colin J

    2016-09-01

    Bilirubin is a potent antioxidant that is produced from the reduction of the heme degradation product biliverdin. In mammalian cells and Cyanobacteria, NADH/NADPH-dependent biliverdin reductases (BVRs) of the Rossmann-fold have been shown to catalyze this reaction. Here, we describe the characterization of Rv2074 from Mycobacterium tuberculosis, which belongs to a structurally and mechanistically distinct family of F420 H2 -dependent BVRs (F-BVRs) that are exclusively found in Actinobacteria. We have solved the crystal structure of Rv2074 bound to its cofactor, F420 , and used this alongside molecular dynamics simulations, site-directed mutagenesis and NMR spectroscopy to elucidate its catalytic mechanism. The production of bilirubin by Rv2074 could exploit the anti-oxidative properties of bilirubin and contribute to the range of immuno-evasive mechanisms that have evolved in M. tuberculosis to allow persistent infection. PMID:27364382

  7. How to use: transcutaneous bilirubinometry.

    PubMed

    O'Connor, Matthew C; Lease, Meredith A; Whalen, Bonny L

    2013-08-01

    The National Institute for Health and Clinical Excellence neonatal jaundice guidelines recommend checking the bilirubin level in all infants with visible jaundice. The gold standard for this measurement is total serum bilirubin (TSB). Transcutaneous bilirubinometry (TcB) is an alternative to TSB that has been validated for clinical use through extensive study. TcB provides many advantages over TSB including instantaneous measurements without requiring a painful lab draw. For infants >35 weeks gestation, TcB can reliably identify infants at risk for severe hyperbilirubinaemia and can decrease the number of TSB measurements obtained. However, paediatric providers should be aware of limitations in clinical use of TcB including decreasing accuracy at higher bilirubin levels, lack of independently validated nomograms for interpretation and limited research regarding its use during phototherapy. PMID:23660389

  8. Effect of omeprazole 20 mg twice daily on duodenogastric and gastro-oesophageal bile reflux in Barrett's oesophagus

    PubMed Central

    Marshall, R; Anggiansah, A; Manifold, D; Owen, W; Owen, W

    1998-01-01

    Background—Both acid and duodenal contents are thought to be responsible for the mucosal damage in Barrett's oesophagus, a condition often treated medically. However, little is known about the effect of omeprazole on duodenogastric reflux (DGR) and duodenogastro-oesophageal reflux (DGOR).
Aims—To study the effect of omeprazole 20 mg twice daily on DGR and DGOR, using the technique of ambulatory bilirubin monitoring.
Methods—Twenty three patients with Barrett's oesophagus underwent manometry followed by 24 hour oesophageal and gastric pH monitoring. In conjunction with pH monitoring, 11 patients (group 1) underwent oesophageal bilirubin monitoring and 12 patients (group 2) underwent gastric bilirubin monitoring, both before and during treatment with omeprazole 20 mg twice daily.
Results—In both groups there was a significant reduction in oesophageal acid (pH<4) reflux (p<0.005) and a significant increase in the time gastric pH was above 4 (p<0.005). In group 1, median total oesophageal bilirubin exposure was significantly reduced from 28.9% to 2.4% (p<0.005). In group 2, median total gastric bilirubin exposure was significantly reduced from 24.9% to 7.2% (p<0.005). 
Conclusions—Treatment of Barrett's oesophagus with omeprazole 20 mg twice daily results in a notable reduction in the exposure of the oesophagus to both acid and duodenal contents. In addition, delivery of duodenal contents to the upper gastric body is reduced. 

 Keywords: bilirubin monitoring; Barrett's oesophagus; omeprazole; pH monitoring; duodenogastric reflux; duodenogastro-oesophageal reflux PMID:9824338

  9. Identification of an A-to-G missense mutation in exon 2 of the UGT1 gene complex that causes Crigler-Najjar syndrome type 2

    SciTech Connect

    Moghrabi, N.; Clarke, D.J.; Boxer, M.; Burchell, B. )

    1993-10-01

    Crigler-Najjar syndrome is an inborn error of metabolism that is characterized by severe unconjugated hyperbilirubinemia. The disease is caused by a deficiency in the hepatic enzyme bilirubin UDP-glucoronosyl-transferase (UGT), which is responsible for the safe elimination of the toxic heme breakdown product bilirubin from the body via bile. Two types of the disease have been classified according to their clinical severity. Crigler-Najjar syndrome type 2 (CN-2) is a less severe form of the disease that is caused by a reduced ability to glucoronidate bilirubin, with serium bilirubin levels ranging from 60 to 340 [mu]M. The recent identification of a large gene locus termed UGT1 that encodes two bilirubin UGTs (UGT1*1 and UGT1*4) and two phenol UGTs (UGT1*02 and UGT1*6) has provided the tools for studying hereditary unconjugated hyperbilirubinemias. Recent analysis of five unrelated CN-1 patients has revealed the presence of several mutations in the UGT1 gene complex. Here, the authors present the first report of a mutation identified in a CN-2 patient and discuss the correlation of this mutation with the severity of the disease. The missense mutation identified in exon 2 of the CN-2 patient's DNA that is shared by several UGT1 genes is predicted to change a glutamine codon (CAG) to an arginine codon (CGG) at residue 331 of the bilirubin UGT isoenzymes, UGT1*1 and UGT1*4, and residue 329 of UGT1*02 and residue 327 of UGT1*6 of the phenol UGT isoenzymes. This agreed with enzymological and immunochemical studies, which demonstrated that the expression of all UGT1 proteins was affected in the CN-2 patient. 12 refs., 1 fig.

  10. UGT1A1 promoter polymorphisms and the development of hyperbilirubinemia and gallbladder disease in children with sickle cell anemia.

    PubMed

    Carpenter, Shannon L; Lieff, Susan; Howard, Thad A; Eggleston, Barry; Ware, Russell E

    2008-10-01

    Genetic modifiers contribute to phenotypic variability in patients with sickle cell anemia (SCA). The influence of the bilirubin UDP-glucuronosyltransferase (UGT) 1A1 (TA)(n)TAA promoter polymorphism on bilirubin levels and gallbladder disease in SCA was examined using prospectively collected data from the Cooperative Study of Sickle Cell Disease. A total of 324 children with HbSS (median age 6.9 years) had UGT1A1 genotyping; 243 (75%) had common (TA)(6) or (TA)(7) alleles, whereas 81 (25.0%) had variant (TA)(5) or (TA)(8) alleles. The UGT1A1 genotype significantly influenced average bilirubin levels for the common alleles: 6/6 genotype = 2.36 +/- 1.13 mg/dL, 6/7 genotype = 2.90 +/- 1.54 mg/dL, and 7/7 genotype = 4.24 +/- 2.11 mg/dL (P < 0.0001). Thirty-nine percent of children with the 7/7 genotype had documented gallbladder disease, compared with 18.2% with the 6/7 genotype and only 9.9% with the wildtype 6/6 UGT1A1 genotype (P = 0.001). To analyze the (TA)(5) and (TA)(8) variant alleles, three groups were generated, showing increasing bilirubin levels with increasing TA repeats and age. Group 3 (genotypes 6/8, 7/7, and 7/8) had a significantly greater rate of bilirubin change than Groups 1 (genotypes 5/6, 5/7, and 6/6) or 2 (genotype 6/7). These results validate previous smaller studies and confirm that the UGT1A1 promoter polymorphism exerts a powerful influence on bilirubin levels and the development of gallbladder disease in children with SCA. UGT1A1 genotyping should be considered as a screening tool for predicting children most likely to develop gallbladder disease at a young age. PMID:18756540

  11. Lineage-Specific Changes in Biomarkers in Great Apes and Humans.

    PubMed

    Ronke, Claudius; Dannemann, Michael; Halbwax, Michel; Fischer, Anne; Helmschrodt, Christin; Brügel, Mathias; André, Claudine; Atencia, Rebeca; Mugisha, Lawrence; Scholz, Markus; Ceglarek, Uta; Thiery, Joachim; Pääbo, Svante; Prüfer, Kay; Kelso, Janet

    2015-01-01

    Although human biomedical and physiological information is readily available, such information for great apes is limited. We analyzed clinical chemical biomarkers in serum samples from 277 wild- and captive-born great apes and from 312 healthy human volunteers as well as from 20 rhesus macaques. For each individual, we determined a maximum of 33 markers of heart, liver, kidney, thyroid and pancreas function, hemoglobin and lipid metabolism and one marker of inflammation. We identified biomarkers that show differences between humans and the great apes in their average level or activity. Using the rhesus macaques as an outgroup, we identified human-specific differences in the levels of bilirubin, cholinesterase and lactate dehydrogenase, and bonobo-specific differences in the level of apolipoprotein A-I. For the remaining twenty-nine biomarkers there was no evidence for lineage-specific differences. In fact, we find that many biomarkers show differences between individuals of the same species in different environments. Of the four lineage-specific biomarkers, only bilirubin showed no differences between wild- and captive-born great apes. We show that the major factor explaining the human-specific difference in bilirubin levels may be genetic. There are human-specific changes in the sequence of the promoter and the protein-coding sequence of uridine diphosphoglucuronosyltransferase 1 (UGT1A1), the enzyme that transforms bilirubin and toxic plant compounds into water-soluble, excretable metabolites. Experimental evidence that UGT1A1 is down-regulated in the human liver suggests that changes in the promoter may be responsible for the human-specific increase in bilirubin. We speculate that since cooking reduces toxic plant compounds, consumption of cooked foods, which is specific to humans, may have resulted in relaxed constraint on UGT1A1 which has in turn led to higher serum levels of bilirubin in humans. PMID:26247603

  12. Lineage-Specific Changes in Biomarkers in Great Apes and Humans

    PubMed Central

    Ronke, Claudius; Dannemann, Michael; Halbwax, Michel; Fischer, Anne; Helmschrodt, Christin; Brügel, Mathias; André, Claudine; Atencia, Rebeca; Mugisha, Lawrence; Scholz, Markus; Ceglarek, Uta; Thiery, Joachim; Pääbo, Svante; Prüfer, Kay; Kelso, Janet

    2015-01-01

    Although human biomedical and physiological information is readily available, such information for great apes is limited. We analyzed clinical chemical biomarkers in serum samples from 277 wild- and captive-born great apes and from 312 healthy human volunteers as well as from 20 rhesus macaques. For each individual, we determined a maximum of 33 markers of heart, liver, kidney, thyroid and pancreas function, hemoglobin and lipid metabolism and one marker of inflammation. We identified biomarkers that show differences between humans and the great apes in their average level or activity. Using the rhesus macaques as an outgroup, we identified human-specific differences in the levels of bilirubin, cholinesterase and lactate dehydrogenase, and bonobo-specific differences in the level of apolipoprotein A-I. For the remaining twenty-nine biomarkers there was no evidence for lineage-specific differences. In fact, we find that many biomarkers show differences between individuals of the same species in different environments. Of the four lineage-specific biomarkers, only bilirubin showed no differences between wild- and captive-born great apes. We show that the major factor explaining the human-specific difference in bilirubin levels may be genetic. There are human-specific changes in the sequence of the promoter and the protein-coding sequence of uridine diphosphoglucuronosyltransferase 1 (UGT1A1), the enzyme that transforms bilirubin and toxic plant compounds into water-soluble, excretable metabolites. Experimental evidence that UGT1A1 is down-regulated in the human liver suggests that changes in the promoter may be responsible for the human-specific increase in bilirubin. We speculate that since cooking reduces toxic plant compounds, consumption of cooked foods, which is specific to humans, may have resulted in relaxed constraint on UGT1A1 which has in turn led to higher serum levels of bilirubin in humans. PMID:26247603

  13. Role of vitamin C transporters and biliverdin reductase in the dual pro-oxidant and anti-oxidant effect of biliary compounds on the placental-fetal unit in cholestasis during pregnancy

    SciTech Connect

    Perez, Maria J.; Castano, Beatriz; Jimenez, Silvia; Serrano, Maria A.; Gonzalez-Buitrago, Jose M.; Marin, Jose J.G.

    2008-10-15

    Maternal cholestasis causes oxidative damage to the placental-fetal unit that may challenge the outcome of pregnancy. This has been associated with the accumulation of biliary compounds able to induce oxidative stress. However, other cholephilic compounds such as ursodeoxycholic acid (UDCA) and bilirubin have direct anti-oxidant properties. In the present study we investigated whether these compounds exert a protective effect on cholestasis-induced oxidative stress in placenta as compared to maternal and fetal livers, and whether this is due in part to the activation of anti-oxidant mechanisms involving vitamin C uptake and biliverdin/bilirubin recycling. In human placenta (JAr) and liver (HepG2) cells, deoxycholic acid (DCA) similar rates of free radical generation. In JAr (not HepG2), the mitochondrial membrane potential and cell viability were impaired by low DCA concentrations; this was partly prevented by bilirubin and UDCA. In HepG2, taurocholic acid (TCA) and UDCA up-regulated biliverdin-IX{alpha} reductase (BVR{alpha}) and the vitamin C transporter SVCT2 (not SVCT1), whereas bilirubin up-regulated both SVCT1 and SVCT2. In JAr, TCA and UDCA up-regulated BVR{alpha}, SVCT1 and SVCT2, whereas bilirubin up-regulated only SVCT2. A differential response to these compounds of nuclear receptor expression (SXR, CAR, FXR and SHP) was found in both cell types. When cholestasis was induced in pregnant rats, BVR{alpha}, SVCT1 and SVCT2 expression in maternal and fetal livers was stimulated, and this was further enhanced by UDCA treatment. In placenta, only BVR{alpha} was up-regulated. In conclusion, bilirubin accumulation and UDCA administration may directly and indirectly protect the placental-fetal unit from maternal cholestasis-induced oxidative stress.

  14. Life-Long Correction of Hyperbilirubinemia with a Neonatal Liver-Specific AAV-Mediated Gene Transfer in a Lethal Mouse Model of Crigler–Najjar Syndrome

    PubMed Central

    Bortolussi, Giulia; Zentillin, Lorena; Vaníkova, Jana; Bockor, Luka; Bellarosa, Cristina; Mancarella, Antonio; Vianello, Eleonora; Tiribelli, Claudio; Giacca, Mauro; Vitek, Libor

    2014-01-01

    Abstract Null mutations in the UGT1A1 gene result in Crigler–Najjar syndrome type I (CNSI), characterized by severe hyperbilirubinemia and constant risk of developing neurological damage. Phototherapy treatment lowers plasma bilirubin levels, but its efficacy is limited and liver transplantation is required. To find alternative therapies, we applied AAV liver-specific gene therapy to a lethal mouse model of CNSI. We demonstrated that a single neonatal hUGT1A1 gene transfer was successful and the therapeutic effect lasted up to 17 months postinjection. The therapeutic effect was mediated by the presence of transcriptionally active double-stranded episomes. We also compared the efficacy of two different gene therapy approaches: liver versus skeletal muscle transgene expression. We observed that 5–8% of normal liver expression and activity levels were sufficient to significantly reduce bilirubin levels and maintain lifelong low plasma bilirubin concentration (3.1±1.5 mg/dl). In contrast, skeletal muscle was not able to efficiently lower bilirubin (6.4±2.0 mg/dl), despite 20–30% of hUgt1a1 expression levels, compared with normal liver. We propose that this remarkable difference in gene therapy efficacy could be related to the absence of the Mrp2 and Mrp3 transporters of conjugated bilirubin in muscle. Taken together, our data support the concept that liver is the best organ for efficient and long-term CNSI gene therapy, and suggest that the use of extra-hepatic tissues should be coupled to the presence of bilirubin transporters. PMID:25072305

  15. Early Hepatic Dysfunction Is Associated with a Worse Outcome in Patients Presenting with Acute Respiratory Distress Syndrome: A Post-Hoc Analysis of the ACURASYS and PROSEVA Studies

    PubMed Central

    Dizier, Stéphanie; Forel, Jean-Marie; Ayzac, Louis; Richard, Jean-Christophe; Hraiech, Sami; Lehingue, Samuel; Loundou, Anderson; Roch, Antoine; Guerin, Claude; Papazian, Laurent

    2015-01-01

    Introduction Bilirubin is well-recognized marker of hepatic dysfunction in intensive care unit (ICU) patients. Multiple organ failure often complicates acute respiratory distress syndrome (ARDS) evolution and is associated with high mortality. The effect of early hepatic dysfunction on ARDS mortality has been poorly investigated. We evaluated the incidence and the prognostic significance of increased serum bilirubin levels in the initial phase of ARDS. Methods The data of 805 patients with ARDS were retrospectively analysed. This population was extracted from two recent multicenter, prospective and randomised trials. Patients presenting with ARDS with a ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen < 150 mmHg measured with a PEEP ≥ 5 cm of water were included. The total serum bilirubin was measured at inclusion and at days 2, 4, 7 and 14. The primary objective was to analyse the bilirubin at inclusion according to the 90-day mortality rate. Results The 90-day mortality rate was 33.8% (n = 272). The non-survivors were older, had higher Sepsis-related Organ Failure Assessment (SOFA) score and were more likely to have a medical diagnosis on admission than the survivors. At inclusion, the SOFA score without the liver score (10.3±2.9 vs. 9.0±3.0, p<0.0001) and the serum bilirubin levels (36.1±57.0 vs. 20.5±31.5 μmol/L, p<0.0001) were significantly higher in the non-survivors than in the survivors. Age, the hepatic SOFA score, the coagulation SOFA score, the arterial pH level, and the plateau pressure were independently associated with 90-day mortality in patients with ARDS. Conclusion Bilirubin used as a surrogate marker of hepatic dysfunction and measured early in the course of ARDS was associated with the 90-day mortality rate. PMID:26636318

  16. Molecular diagnosis in Vascular Ehlers-Danlos Syndrome Predicts Pattern of Arterial Involvement and Outcomes

    PubMed Central

    Shalhub, Sherene; Black, James H; Cecchi, Alana C.; Xu, Zhi; Griswold, Ben F; Safi, Hazim J; Milewicz, Dianna M.; McDonnell, Nazli B.

    2015-01-01

    OBJECTIVES The management of arterial pathology in individuals with vascular Ehlers-Danlos syndrome (vEDS) remains a challenge. Here we describe the correlation between COL3A1 gene mutation type and the clinical phenotype in individuals with vEDS. METHODS Individuals with confirmed molecular diagnoses of vEDS were enrolled in a multi institutional natural history study. Data collected included demographics, clinical and family histories, arterial pathology (aneurysm, dissection, and rupture), operative details, and autopsy reports. Individuals were classified into two cohorts based on the type of COL3A1 mutations and their effect on the amount of normal collagen produced: MIN group had mutations that lead to minimal (10–15%) production of normal type III collagen and HI group had haploinsufficiency mutations that lead to production of half the normal type III collagen. RESULTS A cohort of 68 (72%) individuals from 56 families had arterial pathology (44% male, 13% HI). The HI group was older at the time of their first vascular event (mean 42 years, range 26–58 vs. 33 years, range 8–62, P = .016). The HI group had a higher incidence of aortic pathology compared to the MIN group (56% vs. 21%. P = .025). Visceral arterial pathology was seen in 43 arteries in 23 individuals in the MIN group versus only a single artery in 5 individuals in the HI group. Emergent surgical procedures were more likely to be undertaken when vEDS diagnosis was not known (81% vs. 41%, P = .005) and the majority of these procedures were open surgical repair compared to endovascular repair (81% vs. 19%, P = .019). In the elective setting, there was equal use of open and endovascular repair. Post-operative complications were highest when the diagnosis of vEDS was not known (62% vs. 14%, P < .001) and when procedures were undertaken in an emergency setting (5% vs. 55% P < .001). There was no mortality due to arterial complications in the HI cohort and 21% in the MIN cohort (P = .132

  17. Novel mutations in the Dubin-Johnson syndrome gene ABCC2/MRP2 and associated biochemical changes.

    PubMed

    Devgun, Manjit S; El-Nujumi, Adil M; O'Dowd, Geraldine J; Barbu, Véronique; Poupon, Raoul

    2012-11-01

    A patient with sepsis and jaundice was admitted for diagnosis and treatment. Associated biochemical changes included increased C-reactive protein, conjugated bilirubin and gamma-glutamyltransferase, the duration of which was protracted. High urine coproporphyrin isomer-1 and immunostaining of liver tissue suggested Dubin-Johnson syndrome. DNA sequencing using polymerase chain reaction amplification of the ABCC2 gene revealed the patient to have a compound heterozygous variant of MRP2, a molecule involved in canalicular transport of bilirubin. There was a history of jaundice since infancy. PMID:23065530

  18. Detecting jaundice by using digital image processing

    NASA Astrophysics Data System (ADS)

    Castro-Ramos, J.; Toxqui-Quitl, C.; Villa Manriquez, F.; Orozco-Guillen, E.; Padilla-Vivanco, A.; Sánchez-Escobar, JJ.

    2014-03-01

    When strong Jaundice is presented, babies or adults should be subject to clinical exam like "serum bilirubin" which can cause traumas in patients. Often jaundice is presented in liver disease such as hepatitis or liver cancer. In order to avoid additional traumas we propose to detect jaundice (icterus) in newborns or adults by using a not pain method. By acquiring digital images in color, in palm, soles and forehead, we analyze RGB attributes and diffuse reflectance spectra as the parameter to characterize patients with either jaundice or not, and we correlate that parameters with the level of bilirubin. By applying support vector machine we distinguish between healthy and sick patients.

  19. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for UGT1A1 and Atazanavir Prescribing.

    PubMed

    Gammal, R S; Court, M H; Haidar, C E; Iwuchukwu, O F; Gaur, A H; Alvarellos, M; Guillemette, C; Lennox, J L; Whirl-Carrillo, M; Brummel, S S; Ratain, M J; Klein, T E; Schackman, B R; Caudle, K E; Haas, D W

    2016-04-01

    The antiretroviral protease inhibitor atazanavir inhibits hepatic uridine diphosphate glucuronosyltransferase (UGT) 1A1, thereby preventing the glucuronidation and elimination of bilirubin. Resultant indirect hyperbilirubinemia with jaundice can cause premature discontinuation of atazanavir. Risk for bilirubin-related discontinuation is highest among individuals who carry two UGT1A1 decreased function alleles (UGT1A1*28 or *37). We summarize published literature that supports this association and provide recommendations for atazanavir prescribing when UGT1A1 genotype is known (updates at www.pharmgkb.org). PMID:26417955

  20. Spontaneous improvement in sensorineural hearing loss developed as a complication of neonatal hyperbilirubinemia.

    PubMed

    Khalid, Sameen; Qadir, Maqbool; Salat, Muhammad Sohail

    2015-09-01

    Icterus neonatorum, or neonatal jaundice, is defined as a total serum bilirubin level above 5mg/dl. Acute bilirubin encephalopathy and kernicterus are known to be the two major complications associated with it, resulting in neurotoxic effects, including sensorineural hearing loss, hypotonia, delayed motor skills and intellectual deficits. We report two similar cases of neonatal jaundice requiring exchange transfusion that subsequently developed sensorineural hearing loss. Follow-up at the end of 1year revealed spontaneous recovery of hearing with normal speech. This report aims at increasing awareness of this condition among physicians to allow early detection of risk factors and prompt management and follow-up. PMID:26338755

  1. [Clofibrate for the treatment of hyperbilirubinemia in neonates born at term: a double blind controlled study (author's transl)].

    PubMed

    Lindenbaum, A; Hernandorena, X; Vial, M; Benattar, C; Janaud, J C; Dehan, M; Foliot, A; Leluc, R; Gabilan, J C

    1981-12-01

    A double blind controlled study of the therapeutic effect of clofibrate, an inductor of bilirubin glucuronyl transferase, was performed in neonates born at term and presenting with physiologic jaundice. 47 children were treated with a single oral dose of clofibrate. 46 control children were given corn oil alone. Results show that mean plasma bilirubin levels are significantly lower in the treated group as compared with the control group, from the 16th hour of treatment, if there is no ABO incompatibility. Clofibrate treatment also resulted in a shorter duration of jaundice and a restricted use of phototherapy. No undesirable side-effect was observed. PMID:7036932

  2. Phototherapy in Gunn rats. A study to assess the photobiologically most effective radiant energy and dose/response relationships.

    PubMed

    Ballowitz, L; Geutler, G; Krochmann, J; Pannitschka, R; Roemer, G; Roemer, I

    1977-01-01

    In order to get a more realistic spectral efficiency curve and to evaluate dose/response relationships in phototherapy, homozygous weanling Gunn rats -- nondepilated, with fur -- were illuminated under standardized conditions with 8 different fluorescent tubes. Some of the tubes were operated with different electric power. Clear spectal differences in the extent and the rapidity of the bilirubin decay could be ascertained. Furthermore, the sharpness of the bilirubin decrease depended on the baseline concentration. For the calculations the animals were therefore divided into 3 groups with starting levels of larger than or equal to 8 mg%, 6.5--7.9 mg% and less than 6.5 mg%. Correlating the spectral power distribution of the lamps with the bilirubin decomposition found in the experiment, the spectral response function s(lambda)bili, rel was calculated by an integral method. A comparison of our results with data from the literature shows that so far near UV radiation was evaluated too high. A new radiometer for digital measuring the effective irradiance Ebili was developed. On a logarithmic scale a comparatively sharp dose/response relationship could be demonstrated in dependence on the measured effective radiant exposure. Serum bilirubin decrease is directly proportional to log Ebili. A dose of about 2.5 mW - h/cm2 is necessary to achieve a constant serum bilirubin decrease at all. Good results were obtained at doses of about 35 mW - h/cm2 with the most efficient being at 160 mW - h/cm2. Highly effective doses can be applied with different types of lamps. However, there are great differences in the time of illumination required. 24 h are necessary with daylight tubes (Osram L 20 W/19) to apply 20 mW - h/cm2, whereas the same dose is already attained after 4 h with BAM blue tubes (Philips). The accuracy of the radiometer was finally controlled by screening Westinghouse special blue and Osram standard blue tubes with black tapes, so that the effective irradiance (Ebili

  3. A decision-making tool for exchange transfusions in infants with severe hyperbilirubinemia in resource-limited settings.

    PubMed

    Olusanya, B O; Iskander, I F; Slusher, T M; Wennberg, R P

    2016-05-01

    Late presentation and ineffective phototherapy account for excessive rates of avoidable exchange transfusions (ETs) in many low- and middle-income countries. Several system-based constraints sometimes limit the ability to provide timely ETs for all infants at risk of kernicterus, thus necessitating a treatment triage to optimize available resources. This article proposes a practical priority-setting model for term and near-term infants requiring ET after the first 48 h of life. The proposed model combines plasma/serum bilirubin estimation, clinical signs of acute bilirubin encephalopathy and neurotoxicity risk factors for predicting the risk of kernicterus based on available evidence in the literature. PMID:26938921

  4. Hemolysis in Preterm Neonates.

    PubMed

    Christensen, Robert D; Yaish, Hassan M

    2016-06-01

    Hemolysis can be an important cause of hyperbilirubinemia in premature and term neonates. It can result from genetic abnormalities intrinsic to or factors exogenous to normal to red blood cells (RBCs). Hemolysis can lead to a relatively rapid increase in total serum/plasma bilirubin, hyperbilirubinemia that is somewhat slow to fall with phototherapy, or hyperbilirubinemia that is likely to rebound after phototherapy. Laboratory methods for diagnosing hemolysis are more difficult to apply, or less conclusive, in preterm infants. Transfusion of donor RBCs can present a bilirubin load that must be metabolized. Genetic causes can be identified by next-generation sequencing panels. PMID:27235204

  5. Glucose-6-Phosphate Dehydrogenase Deficiency and the Need for a Novel Treatment to Prevent Kernicterus.

    PubMed

    Cunningham, Anna D; Hwang, Sunhee; Mochly-Rosen, Daria

    2016-06-01

    Hyperbilirubinemia occurs frequently in newborns, and in severe cases can progress to kernicterus and permanent developmental disorders. Glucose-6-phosphate dehydrogenase (G6PD) deficiency, one of the most common human enzymopathies, is a major risk factor for hyperbilirubinemia and greatly increases the risk of kernicterus even in the developed world. Therefore, a novel treatment for kernicterus is needed, especially for G6PD-deficient newborns. Oxidative stress is a hallmark of bilirubin toxicity in the brain. We propose that the activation of G6PD via a small molecule chaperone is a potential strategy to increase endogenous defense against bilirubin-induced oxidative stress and prevent kernicterus. PMID:27235212

  6. The Preterm Infant: A High-Risk Situation for Neonatal Hyperbilirubinemia Due to Glucose-6-Phosphate Dehydrogenase Deficiency.

    PubMed

    Kaplan, Michael; Hammerman, Cathy; Bhutani, Vinod K

    2016-06-01

    Prematurity and glucose-6-phosphate dehydrogenase (G6PD) deficiency are risk factors for neonatal hyperbilirubinemia. The 2 conditions may interact additively or synergistically, contributing to extreme hyperbilirubinemia, with the potential for bilirubin neurotoxicity. This hyperbilirubinemia is the result of sudden, unpredictable, and acute episodes of hemolysis in combination with immaturity of bilirubin elimination, primarily of conjugation. Avoidance of contact with known triggers of hemolysis in G6PD-deficient individuals will prevent some, but not all, episodes of hemolysis. All preterm infants with G6PD deficiency should be vigilantly observed for the development of jaundice both in hospital and after discharge home. PMID:27235211

  7. [Vascular-type Ehlers-Danlos syndrome incidentally diagnosed at surgical treatment for hemothorax; report of a case].

    PubMed

    Kamiya, Kazunori; Yoshizu, Akira; Kashizaki, Fumihiro

    2013-02-01

    Vascular-type Ehlers-Danlos syndrome(vEDS) is a rare autosomal dominant inherited disorder of the connective tissue, which often causes arterial ruptures and surgical complications. We report the case of a vEDS patient who was incidentally diagnosed at surgical treatment for hemothorax. A 64-year-old woman with a past history of hysterectomy due to excessive bleeding during childbirth visited our hospital complaining of chest pain. Chest computed tomography revealed right pleural effusion suspected of hemothorax and a high density area behind the right anterior chest wall. Emergency thoracoscopy revealed bloody spots throughout the mediastinal pleura, suggestive of bleeding from the right internal thoracic artery. During thoracoscopy, easy bruising of the tissue by surgical manipulation was noted which led us to suspect connective tissue disease. A biochemical analysis by cultured dermal fibroblasts and molecular biological examination established the diagnosis of vEDS. PMID:23381370

  8. Micromachined TWTs for THz Radiation Sources

    NASA Technical Reports Server (NTRS)

    Booske, John H.; vanderWeide, Daniel W.; Kory, Carol L.; Limbach, S.; Downey, Alan (Technical Monitor)

    2001-01-01

    The Terahertz (THz) region of the electromagnetic spectrum (about 300 - 3000 GHz in frequency or about 0.1 - 1 mm free space wavelength) has enormous potential for high-data-rate communications, spectroscopy, astronomy, space research, medicine, biology, surveillance, remote sensing, industrial process control, etc. It has been characterized as the most scientifically rich, yet under-utilized, region of the electromagnetic spectrum. The most critical roadblock to full exploitation of the THz band is lack of coherent radiation sources that are powerful (0.001 - 1.0 W continuous wave), efficient (> 1%), frequency agile (instantaneously tunable over 1% bandwidths or more), reliable, and comparatively inexpensive. To develop vacuum electron device (VED) radiation sources satisfying these requirements, fabrication and packaging approaches must be heavily considered to minimize costs, in addition to the basic interaction physics and circuit design. To minimize size of the prime power supply, beam voltage must be minimized, preferably 10 kV. Solid state sources satisfy the low voltage requirement, but are many orders of magnitude below power, efficiency, and bandwidth requirements. On the other hand, typical fast-wave VED sources in this regime (e.g., gyrotrons, FELs) tend to be large, expensive, high voltage and very high power devices unsuitable for most of the applications cited above. VEDs based on grating or inter-digital (ID) circuits have been researched and developed. However, achieving forward-wave amplifier operation with instantaneous fractional bandwidths > 1% is problematic for these devices with low-energy (< 15 kV) electron beams. Moreover, the interaction impedance is quite low unless the beam-circuit spacing is kept particularly narrow, often leading to significant beam interception. One solution to satisfy the THz source requirements mentioned above is to develop micromachined VEDs, or "micro-VEDs". Among other benefits, micro-machining technologies

  9. Melatonin ameliorates vascular endothelial dysfunction, inflammation, and atherosclerosis by suppressing the TLR4/NF-κB system in high-fat-fed rabbits.

    PubMed

    Hu, Ze-Ping; Fang, Xiao-Ling; Fang, Nan; Wang, Xiao-Bian; Qian, Hai-Yan; Cao, Zhong; Cheng, Yuan; Wang, Bang-Ning; Wang, Yuan

    2013-11-01

    Vascular endothelial dysfunction (VED) and inflammation contribute to the initiation and progression of atherosclerosis. Melatonin (MLT) normalizes lipid profile, improves endothelial function, and possesses anti-inflammatory properties. However, the precise mechanisms are still unclear. This study investigated whether MLT could ameliorate VED, inflammation, and atherosclerosis by suppressing the Toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) system in high-fat-fed rabbits. Rabbits were randomly divided into three groups that received a standard diet (control group), high-cholesterol diet (atherosclerosis group), or high-cholesterol diet plus 10 mg/kg/day MLT (MLT group) for 12 wk. After treatment, high-fat diet significantly increased serum lipid and inflammatory markers in rabbits in atherosclerosis group compared with that in control group. In addition, high-fat diet also induced VED and typical atherosclerotic plaque formation and increased intima/media thickness ratio, which were significantly improved by MLT therapy as demonstrated in MLT group. Histological and immunoblot analysis further showed that high-fat diet enhanced the expressions of TLR4, myeloid differentiation primary response protein (MyD88), and NF-κB p65, but decreased inhibitor of NF-κB (IκB) expression. By contrast, MLT therapy decreased the expressions of TLR4, MyD88, and NF-κB p65 and increased IκB expression. This study has demonstrated that MLT ameliorates lipid metabolism, VED, and inflammation and inhibits the progression of atherosclerosis in high-fat-fed rabbits. Moreover, our study indicates for the first time that suppression of the TLR4/NF-κB system in local vasculature with atherosclerotic damage is important for the protective effects of MLT. PMID:24006943

  10. Optimum connecting dampers to reduce the seismic responses of parallel structures

    NASA Astrophysics Data System (ADS)

    Zhu, H. P.; Ge, D. D.; Huang, X.

    2011-04-01

    Parameters of connecting dampers between two adjacent structures and twin-tower structure with large podium are optimized through theoretical analysis. The connecting visco-elastic damper (VED) is represented by the Kelvin model and the connecting viscous fluid damper (VFD) is represented by the Maxwell model. Two optimization criteria are selected to minimize the vibration energy of the primary structure and to minimize the vibration energy of both structures. Two representative numerical examples of adjacent structures and one three-dimensional finite element model of a twin-tower with podium structure are used to verify the correctness of the theoretical approach. On the one hand, by means of theoretical analysis, the first natural circular frequencies and total mass of the two structures can be taken as parameters in the general formula to get the optimal parameters of the coupling dampers. On the other hand, using the Kanai-Tajimi filtered white-noise ground motion model and several actual earthquake records, the appropriate parameters of two types of linking dampers are obtained through extensive parametric studies. By comparison, it can be found that the results of parametric studies are consistent with the results of theoretical studies for the two types of dampers under the two optimization criteria. The effectiveness of VED and VFD is investigated in terms of the seismic response reduction of the neighboring structures. The numerical results demonstrate that the seismic response and vibration energy of parallel structures are mitigated significantly. The performances of VED and VFD are comparable to one another. The explicit formula of VED and VFD can help engineers in application of coupled structure control strategies.

  11. The novel role of fenofibrate in preventing nicotine- and sodium arsenite-induced vascular endothelial dysfunction in the rat.

    PubMed

    Kaur, Jagdeep; Reddy, Krishna; Balakumar, Pitchai

    2010-09-01

    The present study investigated the effect of fenofibrate, an agonist of PPAR-alpha, in nicotine- and sodium arsenite-induced vascular endothelial dysfunction (VED) in rats. Nicotine (2 mg/kg/day, i.p., 4 weeks) and sodium arsenite (1.5 mg/kg/day, i.p., 2 weeks) were administered to produce VED in rats. The scanning electron microscopy study in thoracic aorta revealed that administration of nicotine or sodium arsenite impaired the integrity of vascular endothelium. Further, administration of nicotine or sodium arsenite significantly decreased serum and aortic concentrations of nitrite/nitrate and subsequently reduced acetylcholine-induced endothelium-dependent relaxation. Moreover, nicotine or sodium arsenite produced oxidative stress by increasing serum thiobarbituric acid reactive substances (TBARS) and aortic superoxide generation. However, treatment with fenofibrate (30 mg/kg/day, p.o.) or atorvastatin (30 mg/kg/day p.o., a standard agent) significantly prevented nicotine- and sodium arsenite-induced VED and oxidative stress by improving the integrity of vascular endothelium, increasing the concentrations of serum and aortic nitrite/nitrate, enhancing the acetylcholine-induced endothelium-dependent relaxation and decreasing serum TBARS and aortic superoxide anion generation. Conversely, co-administration of L-NAME (25 mg/kg/day, i.p.), an inhibitor of nitric oxide synthase, markedly attenuated these vascular protective effects of fenofibrate. The administration of nicotine or sodium arsenite altered the lipid profile by increasing serum cholesterol and triglycerides and consequently decreasing high-density lipoprotein levels, which were significantly prevented by treatment with fenofibrate or atorvastatin. It may be concluded that fenofibrate improves the integrity and function of vascular endothelium, and the vascular protecting potential of fenofibrate in preventing the development of nicotine- and sodium arsenite-induced VED may be attributed to its

  12. Reduction in visceral adiposity is highly related to improvement in vascular endothelial dysfunction among obese women: an assessment of endothelial function by radial artery pulse wave analysis.

    PubMed

    Park, Si-Hoon; Shim, Kyung-Won

    2005-08-31

    Because obesity is frequently complicated by other cardiovascular risk factors, the impact of a reduction in visceral adiposity on vascular endothelial dysfunction (VED) in obese patients is difficult to determine. In the present study, we evaluated the impact of a reduction in visceral adiposity on VED in obese women. Thirty-six premenopausal obese women (BMI >/= 25 kg/m2) without complications were enrolled in the study. VED was evaluated by determining the augmentation index (AIx) from radial artery pulse waves obtained by applanation tonometry. Changes in AIx in response to nitroglycerin- induced endothelium-independent vasodilatation (DeltaAIx-NTG) and in response to salbutamol administration (DeltaAIx-Salb) were determined before and after weight reduction. After a 12-week weight reduction program, the average weight loss was 7.96 +/- 3.47 kg, with losses of 21.88 +/- 20.39 cm2 in visceral fat areas (p < 0.001). Pulse wave analysis combined with provocative pharmacological testing demonstrated preserved endothelium-independent vasodilation in healthy premenopausal obese women (DeltaAIx-NTG: 31.36 +/- 9.80% before weight reduction vs. 28.25 +/- 11.21% after weight reduction, p > 0.1) and an improvement in endothelial-dependent vasodilation following weight reduction (DeltaAIx-Salb: 10.03 +/- 6.49% before weight reduction vs. 19.33 +/- 9.28% after reduction, p < 0.001). A reduction in visceral adipose tissue was found to be most significantly related to an increase in DeltaAIx-Salb (beta=-0.57, p < 0.001). A reduction in visceral adiposity was significantly related to an improvement in VED. This finding suggests that reduction of visceral adiposity may be as important as the control of other major risk factors in the prevention of atherosclerosis in obese women. PMID:16127776

  13. Astronomy of the Vedic Age

    NASA Astrophysics Data System (ADS)

    Ôhashi, Yukio

    Aryans who produced Vedic literature migrated to India in the middle of the second millennium BC. After this, they gradually developed astronomical knowledge which was associated with local climate, agriculture, and their predecessors' culture. Toward the end of the Vedic period, sometime around the middle of the first millennium BC, the Vedic calendrical astronomy text entitled Jyotiṣa-vedāṅga was created.

  14. Resistance of nanofill and nanohybrid resin composites to toothbrush abrasion with calcium carbonate slurry.

    PubMed

    Suzuki, Toshimitsu; Kyoizumi, Hideaki; Finger, Werner J; Kanehira, Masafumi; Endo, Tatsuo; Utterodt, Andreas; Hisamitsu, Hisashi; Komatsu, Masashi

    2009-11-01

    The aim of this study was to investigate the wear of four nanofilled resin composites using simulated toothbrushing for 50,000 cycles with calcium carbonate slurry. The depth of abrasion and roughness (Ra) were measured after each 10,000 brushing cycle. The surface texture of the worn samples was examined by SEM.The wear depths of the nanofill Filtek Supreme XT (FIL), the nanohybrides Grandio (GRA), Tetric EvoCeram (TET), and Venus Diamond (VED) increased linearly with numbers of brushing cycles or approximately 80, 12, 600, and 60 mum, respectively after 50,000 strokes. Surface roughness showed virtually no change between 10,000 and 50,000 brushing cycles; the ranking order was TET < FIL < GRA < VED. FIL showed rather uniform abrasion with nanoclusters protruding from the surface. TET was very smoothly abraded without signs of debonding of the prepolymerized particles, whereas GRA and VED showed pronounced wear of the matrix polymer surrounding larger glass filler particles. PMID:20019422

  15. Transvenous Embolization for Carotid-Cavernous Fistula in a Patient with Vascular Type of Ehlers-Danlos Syndrome—Direct Superior Ophthalmic Vein Approach: Case Report

    PubMed Central

    TANAKA, Teppei; HAYAKAWA, Motoharu; SADATO, Akiyo; ADACHI, Kazuhide; WATABE, Takeya; MAEDA, Shingo; OHMURA, Masahiro; HIROSE, Yuichi

    2014-01-01

    The vascular type of Ehlers-Danlos syndrome (vEDS) is an autosomal dominant hereditary disease characterized by connective tissue fragility throughout the body, including the arteries, viscera, and gastrointestinal tract. We report a case in which we performed transvenous embolization (TVE) via direct superior ophthalmic vein (SOV) approach to treat a direct carotid-cavernous fistula (CCF) in a patient with Ehlers-Danlos syndrome (EDS). The patient was a 37-year-old woman who developed tinnitus in her left ear and a headache during examination in the outpatient clinic of another hospital in order to make a definitive diagnosis of vEDS, and she was referred to our hospital and examined. Based on the results of all of the studies she was diagnosed with a CCF. Conservative treatment was attempted, but was not very effective. Because of progressing aphasia, TVE was performed via the SOV direct cut. There were no intraoperative or postoperative complications. It has been reported that cerebral angiography is generally contraindicated in vEDS and that the morbimortality associated with endovascular treatment is very high. When performing treatment it is necessary to be sufficiently aware of the risks it entails. PMID:24418783

  16. The Immune Response to Herpes Simplex Virus Encephalitis in Mice Is Modulated by Dietary Vitamin E12

    PubMed Central

    Sheridan, Patricia A.; Beck, Melinda A.

    2008-01-01

    Herpes simplex virus encephalitis (HSE) is the most common fatal sporadic encephalitis in humans. HSE is primarily caused by herpes simplex virus (HSV)-1 infection of the brain. HSE results in increased levels of oxidative stress, including the production of reactive oxygen species, free radicals, and neuroinflammation. The most biologically active form of vitamin E (VE) is α-tocopherol (α-TOC). In cellular membranes, α-TOC prevents lipid peroxidation by scavenging free radicals and functioning as an antioxidant. Supplementation with VE has been shown to decrease immunosenescence, improve immune function, and may be neuroprotective. To determine how VE deficiency and VE supplementation would alter the pathogenesis of HSE, we placed weanling male BALB/cByJ mice on VE-deficient (VE-D), VE-adequate (VE-A), or 10× VE-supplemented diets for 4 wk, and then infected the mice intranasally with HSV-1. VE-D mice had more severe symptoms of encephalitis than VE-A mice, including weight loss, keratitis, hunched posture, and morbidity. VE-D mice had increased cytokine and chemokine expression in the brain and increased viral titers. In contrast, VE supplementation failed to decrease cytokine production and had no effect on viral titer. We demonstrated that adequate levels of VE are important in limiting HSE pathology and that 10× supplementation does not enhance protection. PMID:18156415

  17. Estimation of skin concentrations of topically applied lidocaine at each depth profile.

    PubMed

    Oshizaka, Takeshi; Kikuchi, Keisuke; Kadhum, Wesam R; Todo, Hiroaki; Hatanaka, Tomomi; Wierzba, Konstanty; Sugibayashi, Kenji

    2014-11-20

    Skin concentrations of topically administered compounds need to be considered in order to evaluate their efficacies and toxicities. This study investigated the relationship between the skin permeation and concentrations of compounds, and also predicted the skin concentrations of these compounds using their permeation parameters. Full-thickness skin or stripped skin from pig ears was set on a vertical-type diffusion cell, and lidocaine (LID) solution was applied to the stratum corneum (SC) in order to determine in vitro skin permeability. Permeation parameters were obtained based on Fick's second law of diffusion. LID concentrations at each depth of the SC were measured using tape-stripping. Concentration-depth profiles were obtained from viable epidermis and dermis (VED) by analyzing horizontal sections. The corresponding skin concentration at each depth was calculated based on Fick's law using permeation parameters and then compared with the observed value. The steady state LID concentrations decreased linearly as the site became deeper in SC or VED. The calculated concentration-depth profiles of the SC and VED were almost identical to the observed profiles. The compound concentration at each depth could be easily predicted in the skin using diffusion equations and skin permeation data. Thus, this method was considered to be useful for promoting the efficient preparation of topically applied drugs and cosmetics. PMID:25158219

  18. A Recombinant G Protein Plus Cyclosporine A-Based Respiratory Syncytial Virus Vaccine Elicits Humoral and Regulatory T Cell Responses against Infection without Vaccine-Enhanced Disease.

    PubMed

    Li, Chaofan; Zhou, Xian; Zhong, Yiwei; Li, Changgui; Dong, Aihua; He, Zhonghuai; Zhang, Shuren; Wang, Bin

    2016-02-15

    Respiratory syncytial virus (RSV) infection can cause severe disease in the lower respiratory tract of infants and older people. Vaccination with a formalin-inactivated RSV vaccine (FI-RSV) and subsequent RSV infection has led to mild to severe pneumonia with two deaths among vaccinees. The vaccine-enhanced disease (VED) was recently demonstrated to be due to an elevated level of Th2 cell responses following loss of regulatory T (Treg) cells from the lungs. To induce high levels of neutralizing Abs and minimize pathogenic T cell responses, we developed a novel strategy of immunizing animals with a recombinant RSV G protein together with cyclosporine A. This novel vaccine induced not only a higher level of neutralizing Abs against RSV infection, but, most importantly, also significantly higher levels of Treg cells that suppressed VED in the lung after RSV infection. The induced responses provided protection against RSV challenge with no sign of pneumonia or bronchitis. Treg cell production of IL-10 was one of the key factors to suppress VED. These finding indicate that G protein plus cyclosporine A could be a promising vaccine against RSV infection in children and older people. PMID:26792805

  19. 40 CFR 799.5055 - Hazardous waste constituents subject to testing.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... measure of clotting potential such as clotting time, prothrombin time, thromboplastin time, or platelet count. (2) Certain clinical biochemistry determinations on blood shall be carried out at least two times... nitrogen, albumen blood creatinine, total bilirubin and total serum protein measurements....

  20. 40 CFR 799.5055 - Hazardous waste constituents subject to testing.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... measure of clotting potential such as clotting time, prothrombin time, thromboplastin time, or platelet count. (2) Certain clinical biochemistry determinations on blood shall be carried out at least two times... nitrogen, albumen blood creatinine, total bilirubin and total serum protein measurements....

  1. 40 CFR 799.5055 - Hazardous waste constituents subject to testing.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... measure of clotting potential such as clotting time, prothrombin time, thromboplastin time, or platelet count. (2) Certain clinical biochemistry determinations on blood shall be carried out at least two times... nitrogen, albumen blood creatinine, total bilirubin and total serum protein measurements....

  2. 40 CFR 799.5055 - Hazardous waste constituents subject to testing.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... measure of clotting potential such as clotting time, prothrombin time, thromboplastin time, or platelet count. (2) Certain clinical biochemistry determinations on blood shall be carried out at least two times... nitrogen, albumen blood creatinine, total bilirubin and total serum protein measurements....

  3. Severe Hemolysis in a Patient With Erythrocytosis During Coupled Plasma Filtration Adsorption Therapy Was Prevented by Changing From Membrane-Based Technique to a Centrifuge-Based One.

    PubMed

    Fan, Rong; Wu, Buyun; Kong, Ling; Gong, Dehua

    2016-01-01

    Coupled plasma filtration adsorption (CPFA) usually adopts membrane to separate plasma from blood. Here, we reported a case with erythrocytosis experienced severe hemolysis and membrane rupture during CPFA, which was avoided by changing from membrane-based technique to a centrifuge-based one. A 66-year-old man was to receive CPFA for severe hyperbilirubinemia (total bilirubin 922 μmol/L, direct bilirubin 638 μmol/L) caused by obstruction of biliary tract. He had erythrocytosis (hemoglobin 230 g/L, hematocrit 0.634) for years because of untreated tetralogy of Fallot. Severe hemolysis and membrane rupture occurred immediately after blood entering into the plasma separator even at a low flow rate (50 mL/min) and persisted after changing a new separator. Finally, centrifugal plasma separation technique was used for CPFA in this patient, and no hemolysis occurred. After 3 sessions of CPFA, total bilirubin level decreased to 199 μmol/L with an average decline by 35% per session. Thereafter, the patient received endoscopic biliary stent implantation, and total bilirubin level returned to nearly normal. Therefore, centrifugal-based plasma separation can also be used in CPFA and may be superior to a membrane-based one in patients with hyperviscosity. PMID:25909925

  4. Gallbladder visualization during technetium-99m-labeled red cell scintigraphy for gastrointestinal bleeding

    SciTech Connect

    Brill, D.R.

    1985-12-01

    Localization of radionuclide activity in the gallbladder was seen on delayed views following injection of 99mTc-labeled red blood cells for gastrointestinal bleeding in five patients. The mechanism for this unusual finding probably relates to labeling of heme, the biochemical precursor of bilirubin. All patients had had prior transfusions. All but one had severe renal impairment, probably an important predisposing factor.

  5. Uncommon cause of acute encephalopathy in liver cirrhosis.

    PubMed

    Dieuvil, Monique; Malaty, John

    2016-01-01

    A 49-year-old woman with a medical history of alcoholic cirrhosis status post-transjugular intrahepatic portosystemic shunt (post-TIPS) in 2012, and ongoing alcohol abuse, presented to the hospital, with haematuria. CT intravenous pyelogram (IVP) was normal except for 'a large intrahepatic cystic mass adjacent to the TIPS, causing intrahepatic biliary duct dilation'. The patient also presented with acute encephalopathy, jaundice, right upper quadrant abdominal pain and hyperbilirubinaemia (total bilirubin of 8.1 mg/dL with direct bilirubin of 3.0 mg/dL). She remained encephalopathic despite adequate treatment for alcohol withdrawal, hepatic encephalopathy and enterococcus urinary tract infection. MRI of the abdomen later confirmed presence of an obstructing biloma. The biloma, drained by CT-guided percutaneous drains, demonstrated an Escherichia coli and ESBL Klebsiella infection. The patient's encephalopathy completely resolved after treatment of the infected biloma. With adequate drainage, her hyperbilirubinaemia resolved to her post-TIPS baseline (total bilirubin of 3.7 mg/dL with direct bilirubin of 3.3 mg/dL). PMID:27194673

  6. Evaluation of Neonatal Hemolytic Jaundice: Clinical and Laboratory Parameters

    PubMed Central

    Cherepnalkovski, Anet Papazovska; Krzelj, Vjekoslav; Zafirovska-Ivanovska, Beti; Gruev, Todor; Markic, Josko; Aluloska, Natasa; Zdraveska, Nikolina; Piperkovska, Katica

    2015-01-01

    BACKGROUND: Neonatal jaundice that occurs in ABO or Rhesus issoimunisation has been recognized as one of the major risk factors for development of severe hyperbilirubinemia and bilirubin neurotoxicity. AIM: Aim of our study was to investigate clinical and laboratory parameters associated with hemolytic jaundice due to Rh and ABO incompatibility and compare results with the group of unspecific jaundice. MATERIAL AND METHODS: One hundred sixty seven (167) neonatal hyperbilirubinemia cases were included in the study, 24.6% of which presented with ABO/Rhesus type hemolytic jaundice, and the rest with unspecific jaundice. Evaluation included: blood count, reticulocites, serum bilirubin, aminotransferases, blood grouping, and Coombs test, also the day of bilirubin peak, duration of the hyperbilirubinemia, and additional bilirubin measurements. RESULTS: We showed significantly lower mean values of hemoglobin, erythrocytes and hematocrit and significantly higher values of reticulocytes in the group of ABO/Rh incompatibility compared to the group of jaundice of unspecific etiology; also an earlier presentation and a higher-grade jaundice in this group. CONCLUSIONS: The laboratory profile in ABO/Rh isoimmunisation cases depicts hemolytic mechanism of jaundice. These cases carry a significant risk for early and severe hyperbilirubinemia and are eligible for neurodevelopmental follow-up. Hematological parameters and blood grouping are simple diagnostic methods that assist the etiological diagnosis of neonatal hyperbilirubinemia. PMID:27275310

  7. Neonatal jaundice.

    PubMed

    Allen, Daniel

    2016-07-01

    Essential facts The National Institute for Health and Care Excellence (NICE) first published guidelines on jaundice in newborn babies in 2010 and updated them in May. Jaundice is caused by raised bilirubin levels when red blood cells are broken down. PMID:27387624

  8. 29 CFR 1910.1017 - Vinyl chloride.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... appropriate respirators specified in paragraph (d)(3)(i)(A) of 29 CFR 1910.134. (B) Provide an organic vapor... determinations made of: (A) Total bilirubin; (B) Alkaline phosphatase; (C) Serum glutamic oxalacetic transaminase... Suspect Agent or (ii) In accordance with 49 CFR Parts 170 through 189, with the additional legend:...

  9. 29 CFR 1910.1017 - Vinyl chloride.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... appropriate respirators specified in paragraph (d)(3)(i)(A) of 29 CFR 1910.134. (B) Provide an organic vapor... determinations made of: (A) Total bilirubin; (B) Alkaline phosphatase; (C) Serum glutamic oxalacetic transaminase... Suspect Agent or (ii) In accordance with 49 CFR Parts 170 through 189, with the additional legend:...

  10. 75 FR 47475 - Acetamiprid, Mepiquat; Order Denying NRDC’s Objections on Remand: Environmental Protection Agency

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-06

    .... (70 FR 46706 (August 10, 2005)). NRDC sought judicial review of the August, 2005 order, and the U.S..., total bilirubin, albumin, hormones, and enzymes such as alkaline phosphatase, alanine aminotransfersase... Exposure to Pesticides in Food (June 21, 2000). (See 73 FR 42683, 42687 (July 23, 2008)). ii. Exposure...

  11. [Photoprevention or phototherapy in newborn infants born prematurely?].

    PubMed

    Romagnoli, C; Muzii, U; Maggio, L; De Carolis, M P; Zecca, E; Zuppa, A A; Tortorolo, G

    1987-01-01

    The authors studied the effects of different kinds of phototherapy in 186 newborns with a gestational age less than 33 weeks and weighing less than 2500 g. A control group of 60 infants was compared with a group of 31 infants submitted to photoprophylaxis, a group of 54 infants treated with day light, and a group of 41 infants treated with day light + special blue light. As far as the serum bilirubin variations in the first week, the maximum levels attained and the number of exchange transfusions are concerned, phototherapy always proved effective in reducing potentially neurotoxic serum bilirubin concentrations. Among the infants subjected to treatment, those treated with the day light showed a significant smaller decrease of serum bilirubin compared to those treated with the day light + special blue light, even if levels above 15 mg/dl were found in a similar percentage. Only 3.2% of the babies treated with photoprophylaxis showed serum bilirubin values above 15 mg/dl. The authors conclude that prophylaxis seems to be preferable to other phototherapeutic schedules used in the treatment of hyperbilirubinemia in low gestational age infants. PMID:3658802

  12. Genetics Home Reference: Rotor syndrome

    MedlinePlus

    ... called organic anion transporting polypeptide 1B1 (OATP1B1) and organic anion transporting polypeptide 1B3 (OATP1B3), respectively. Both proteins are found in liver cells; they transport bilirubin and other compounds from the blood into the liver so that ...

  13. Mechanisms of disease: update on the molecular etiology and fundamentals of parenteral nutrition associated cholestasis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Since its introduction into clinical practice in the 1970s, parenteral nutrition has revolutionized the care of premature neonates. Serum transaminase and bilirubin levels are commonly elevated in infants on parenteral nutrition, but their normalization is typical in the setting of short-term admini...

  14. Toxicological evaluation of the hydro-alcohol extract of the dry leaves of Peumus boldus and boldine in rats.

    PubMed

    Almeida, E R; Melo, A M; Xavier, H

    2000-03-01

    The hydro-alcohol extract of the dry leaves of Peumus boldus and boldine, showed abortive and teratogenic action and changes in the blood levels of bilirubin, cholesterol, glucose, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and urea in rats. The long term administration of the extract and boldine did not cause histological modification during a period of 90 days. PMID:10685105

  15. [Conservative treatment of echinococcus alveolaris of the liver: preliminary observations (author's transl)].

    PubMed

    Starke, J

    1979-08-10

    Mebendazol (Vermox) was given for six months at an oral daily dose of 2 g to three patients with inoperable infestation of the liver by Echinococcus alveolaris. In two patients the general state improved greatly, with reduction in the size of the liver infiltrate, regression in serum bilirubin and alkaline phosphatase levels. Treatment continues in the third case. PMID:89026

  16. Brainstem Evoked Response Audiometry (BERA) in Neonates with Hyperbillirubinemia.

    PubMed

    Soni, Annanya; Kanaujia, Surendra Kumar; Kaushik, Sandeep

    2016-09-01

    (1) To study the BERA changes in neonates with unconjugated hyperbilirubinemia. (2) To compare the BERA changes in the neonates with unconjugated hyperbilirubinemia before and after therapy. Thirty consecutive term appropriate for gestational age (AGA) neonates presenting to NICU with total serum bilirubin requiring intervention (using the American Academy of Pediatrics guidelines) were included in the study as cases and thirty normal term AGA neonates with uneventful peri-natal period and a maximum measured serum bilirubin <12 mg/dl in case of term baby were included as controls after obtaining informed consent. Initial BERA was done within 3-24 h of hospitalization after obtaining informed consent from parents, at the time of discharge and at 3 month followup. Machine used for recording BERA was intelligent hearing system version 3.3. In our study out of the 30 cases 10 (33.3 %) cases were found to have BERA changes in the form of absent wave forms, raised threshold, prolonged latencies or prolonged inter peak latencies. In our study, it was observed that there was statistically significant correlation (p value < 0.005) between increasing bilirubin level and BERA changes. Correlation of the findings of this study with previous few studies indicates that BERA can be used as a useful non invasive tool to determine auditory functions in the neonate especially changes of early bilirubin toxicity. PMID:27508136

  17. Development and optimization of a noncontact optical device for online monitoring of jaundice in human subjects.

    PubMed

    Polley, Nabarun; Saha, Srimoyee; Singh, Soumendra; Adhikari, Aniruddha; Das, Sukhen; Choudhury, Bhaskar Roy; Pal, Samir Kumar

    2015-06-01

    Jaundice is one of the notable markers of liver malfunction in our body, revealing a significant rise in the concentration of an endogenous yellow pigment bilirubin. We have described a method for measuring the optical spectrum of our conjunctiva and derived pigment concentration by using diffused reflection measurement. The method uses no prior model and is expected to work across the races (skin color) encompassing a wide range of age groups. An optical fiber-based setup capable of measuring the conjunctival absorption spectrum from 400 to 800 nm is used to monitor the level of bilirubin and is calibrated with the value measured from blood serum of the same human subject. We have also developed software in the LabVIEW platform for use in online monitoring of bilirubin levels in human subjects by nonexperts. The results demonstrate that relative absorption at 460 and 600 nm has a distinct correlation with that of the bilirubin concentration measured from blood serum. Statistical analysis revealed that our proposed method is in agreement with the conventional biochemical method. The innovative noncontact, low-cost technique is expected to have importance in monitoring jaundice in developing/underdeveloped countries, where the inexpensive diagnosis of jaundice with minimally trained manpower is obligatory. PMID:26052974

  18. Non-invasive physiological measurements

    SciTech Connect

    Rolfe, P.

    1983-01-01

    This book discusses the diagnostic techniques of nondestructive type for monitoring the physiology of various organ systems. The topics covered are: non-invasive assessment of gastric activity; uterine activity, intestinal activity; monitoring of fetal cardiovascular system and bilirubin physiology of infants. Respiratory system of infants is monitored and ultrasonography of heart is discussed.

  19. HCC size: platelets, gamma glutamyl transpeptidase and alkaline phosphatase

    PubMed Central

    Carr, Brian I.; Guerra, Vito

    2013-01-01

    Background Thrombocytopenia is a cirrhosis surrogate, which is associated with HCC development. Aims To compare clinical characteristics of HCC in presence and absence of thrombocytopenia. Methods Baseline clinical data of a large cohort of randomly presenting, biopsy-proven HCC patients was examined for phenotypic patterns, after ordering by tumor size and sub-division into tumor size terciles. Results Small size tercile I patients had lowest platelet counts. Patients with higher platelets within each size tercile had lowest bilirubin and PT and higher GGTP and ALKP levels. When patients with similar platelet and bilirubin levels were compared, AFP, GGTP and ALKP were significantly increased in patients with larger tumors and in presence of PVT. Large size tercile III patients without thrombocytopenia, had larger tumors, higher GGTP and ALKP and lower bilirubin levels than patients with thrombocytopenia. Conclusions Thrombocytopenia occurred in 40.7% of patients with smaller tumors, but only 11.3% with larger tumors. Patients without thrombocytopenia had elevated GGTP and ALKP and lower bilirubin levels, regardless of tumor size, but they also had larger tumors within the large tumor tercile. PMID:23988857

  20. Refractory obstructive jaundice in a child affected with thalassodrepanocytosis: a new endoscopic approach

    PubMed Central

    2010-01-01

    Background Liver involvement, including elevated direct-reacting bilirubin levels, is common in patients with sickle cell disease. Fifty to seventy percent of sickle cell patients have pigmented gallstones due to precipitation of unconjugated bilirubin, and cholelithiasis or choledocholithiasis are common complications. The highest prevalence of these complications occurs in patients with Gilbert's syndrome because of the combined effect of increased bilirubin production and reduced bilirubin-diphosphate-glucuronosyltransferase enzyme activity. Cholelithiasis is also a common complication in patients with thalassemia. Endoscopic removal of choledochal stones does not always resolve the clinical picture, as in cases of dysfunction of the Vater's papilla, increased bile density due to persistently impaired bile flow or distortion of the choledocus due to dilatation, or inflammation secondary to gallstone. Case presentation We report here a case of severe and persistent obstructive jaundice in a child affected with thalassodrepanocytosis and Gilbert's syndrome, previously, and unsuccessfully, treated with endoscopic removal of choledochal stones. Deep and thorough biliary washing, and stenting with a new removable polytetrafluoroethylene (PTFE)-covered flared-type stent led to complete resolution of the obstructive jaundice. Conclusions This report shows that an aggressive endoscopic approach in this select category of patients can help resolve the severe complication of hemolytic anemia, thus avoiding surgery. PMID:20942922

  1. Association of neonatal hyperbilirubinemia in breast-fed infants with UGT1A1 or SLCOs polymorphisms.

    PubMed

    Sato, Hiroko; Uchida, Toshihiko; Toyota, Kentaro; Nakamura, Tomohiro; Tamiya, Gen; Kanno, Miyako; Hashimoto, Taeko; Watanabe, Masashi; Aoki, Kuraaki; Hayasaka, Kiyoshi

    2015-01-01

    Neonates have physiologically increased bilirubin production and immature bilirubin metabolism, and present hyperbilirubinemia in association with genetic and or epigenetic factors. We previously reported that maximal body weight loss (inadequate feeding) is an independent risk factor for the development of hyperbilirubinemia in breast-fed Japanese neonates, and the UGT1A1 211G>A genotype becomes a risk factor under conditions of inadequate feeding. We extended the study to the association of other genetic factors, the UGT1A1 (TA)7 and solute-carrier organic anion transporters (SLCOs) polymorphisms with neonatal hyperbilirubinemia. We enrolled 401 full-term Japanese infants who were exclusively breastfeeding and classified them into two groups based on the degree of maximal body weight loss. We analyzed the clinical characteristics and UGT1A1 and SLCOs genotypes. Statistical analysis revealed that maximal body weight loss is the only independent risk factor for the development of neonatal hyperbilirubinemia. UGT1A1, SLCO1B1 and SLCO1B3 polymorphisms become risk factors in neonates showing 10% or greater body weight loss during the neonatal period. Inadequate feeding may increase the bilirubin burden and cause apparent hyperbilirubinemia in neonates, who have a polymorphic change in the genes involved in the transport and/or metabolism of bilirubin. PMID:25391605

  2. [The jaundiced newborn: which early monitoring for a safe discharge?].

    PubMed

    Pratesi, S; Dani, C

    2013-01-01

    Neonatal jaundice is one of the most common causes of prolonged hospital stay or readmission of a near-term or term baby. Reason of concern at early discharge of a jaundiced newborn is that of bilirubin neurotoxicity, even if a serum bilirubin concentration surely toxic for the brain is still unknown. Kernicterus and severe neonatal hyperbilirubinemia are still problems in the third millennium and the American Academy of Pediatrics claimed the pediatric community to increase vigilance in order to reduce the occurrence of these dramatic events. The only existing kernicterus registry is the pilot USA kernicterus registry whose data on 125 kernicteric term and near term babies from 1992 to 2004 have been recently published. Nobody of the kenicteric babies into the USA register had a serum bilirubin levels below 20 mg/dL. All the babies who suffered from kernicteric sequelae were discharged as healthy from hospital and then, 86% of them, readmitted in the first ten days of life. In the majority of babies (69%) a cause of the severe hyperbilirubinemia was not found. Current knowledge on mechanism of neurological damage induced by bilirubin, unfortunately, does not allow to have a universal evidenced based guideline on how to manage neonatal jaundice. Thus, the existing national guidelines contain inevitable differences in the recommended procedure. Waiting for the future italian guidelines the paper illustrates a proposal of management of neonatal jaundice in term or near term newborns based on available scientific evidence and national guidelines published in english language. PMID:24245097

  3. Newborn jaundice - discharge

    MedlinePlus

    ... hours after therapy stops, to make sure the level is not rising again. Possible side effects of phototherapy are watery ... 3 to 5 days old. If the bilirubin level is not too high or not rising quickly, you can do phototherapy at home with ...

  4. Development and optimization of a noncontact optical device for online monitoring of jaundice in human subjects

    NASA Astrophysics Data System (ADS)

    Polley, Nabarun; Saha, Srimoyee; Singh, Soumendra; Adhikari, Aniruddha; Das, Sukhen; Choudhury, Bhaskar Roy; Pal, Samir Kumar

    2015-06-01

    Jaundice is one of the notable markers of liver malfunction in our body, revealing a significant rise in the concentration of an endogenous yellow pigment bilirubin. We have described a method for measuring the optical spectrum of our conjunctiva and derived pigment concentration by using diffused reflection measurement. The method uses no prior model and is expected to work across the races (skin color) encompassing a wide range of age groups. An optical fiber-based setup capable of measuring the conjunctival absorption spectrum from 400 to 800 nm is used to monitor the level of bilirubin and is calibrated with the value measured from blood serum of the same human subject. We have also developed software in the LabVIEW platform for use in online monitoring of bilirubin levels in human subjects by nonexperts. The results demonstrate that relative absorption at 460 and 600 nm has a distinct correlation with that of the bilirubin concentration measured from blood serum. Statistical analysis revealed that our proposed method is in agreement with the conventional biochemical method. The innovative noncontact, low-cost technique is expected to have importance in monitoring jaundice in developing/underdeveloped countries, where the inexpensive diagnosis of jaundice with minimally trained manpower is obligatory.

  5. Serum ultrafiltration for the elimination of endogenous interfering substances in creatinine determination.

    PubMed

    da Fonseca-Wollheim, F; Heinze, K G; Lomsky, K; Schreiner, H

    1988-08-01

    Serum, at neutral pH, was submitted to a simple filtration, using centrifugation in the disposable Centrisart. The ultrafiltrate was similar to serum in its creatinine content but was virtually free from proteins, including protein-bound bilirubin, haemoglobin and lipoproteins. The creatinine concentrations of anicteric serum specimens and the corresponding ultrafiltrates as determined with Jaffé and enzymic procedures show a high correlation and are convertible. With icteric sera the negative interference effect of bilirubin in a particular analytical procedure can be quantified using ultrafiltrate as the reference. It is suggested that ultrafiltration is useful in selected cases for eliminating elevated concentrations of bilirubin, haemoglobin and turbidity, which would interfere in the direct creatinine determination. Relative to the continuous flow methods with dialysis of the analyte, direct methods for creatinine are more susceptible to interference by endogenous factors like hyperbilirubinaemia, hypertriglyceridaemia and haemolysis (1). The negative interference by bilirubin is of special importance, since it interferes in some modifications of the kinetic Jaffé method (2) and in the chromogenic enzymatic method (3). As a simple alternative, we evaluated the use of serum ultrafiltrate for the accurate determination of creatinine by the Jaffé and enzymatic methods, free from interfering by the high-molecular serum matrix and compounds bound to it. PMID:3221182

  6. The linear effects of alpha-thalassaemia, the UGT1A1 and HMOX1 polymorphisms on cholelithiasis in sickle cell disease.

    PubMed

    Vasavda, Nisha; Menzel, Stephan; Kondaveeti, Sheila; Maytham, Emma; Awogbade, Moji; Bannister, Sybil; Cunningham, Juliette; Eichholz, Andrew; Daniel, Yvonne; Okpala, Iheanyi; Fulford, Tony; Thein, Swee Lay

    2007-07-01

    Serum bilirubin levels and predisposition to gallstones in sickle cell disease (SCD) are influenced by genetic variation in the hepatic uridine diphosphate (UDP)-glucuronosyltransferase (UGT1A1) gene, but the association is not consistent. This study investigated whether variation in the gene encoding haem oxygenase (HMOX1), a rate-limiting enzyme upstream of UGT1A in the haem catabolic pathway, and alpha-thalassaemia could explain some of the inconsistent effects. The UGT1A1 [TA](n) and HMOX1 [GT](n) promoter polymorphisms and alpha globin genotypes were determined in 263 SCD patients (199 HbSS, 5 HbS/beta(0), 59 HbSC). Detection of gallstones was based on ultrasound of the liver/biliary tree. Regression analysis showed that serum bilirubin levels and the incidence of gallstones were strongly associated with the number of UGT1A1 [TA] repeats in all subjects (P < 0.0001 and P < 0.01, respectively). While HMOX1 genotype had no effect, co-inheritance of alpha-thalassaemia reduced serum bilirubin levels in all SCD patients independently of the number of UGT1A1 [TA] repeats. Each additional [TA] repeat is associated with an increase in mean serum bilirubin levels of 21% and cholelithiasis risk of 87% in SCD. PMID:17593033

  7. Evanescent field: A potential light-tool for theranostics application

    NASA Astrophysics Data System (ADS)

    Polley, Nabarun; Singh, Soumendra; Giri, Anupam; Pal, Samir Kumar

    2014-03-01

    A noninvasive or minimally invasive optical approach for theranostics, which would reinforce diagnosis, treatment, and preferably guidance simultaneously, is considered to be major challenge in biomedical instrument design. In the present work, we have developed an evanescent field-based fiber optic strategy for the potential theranostics application in hyperbilirubinemia, an increased concentration of bilirubin in the blood and is a potential cause of permanent brain damage or even death in newborn babies. Potential problem of bilirubin deposition on the hydroxylated fiber surface at physiological pH (7.4), that masks the sensing efficacy and extraction of information of the pigment level, has also been addressed. Removal of bilirubin in a blood-phantom (hemoglobin and human serum albumin) solution from an enhanced level of 77 μM/l (human jaundice >50 μM/l) to ˜30 μM/l (normal level ˜25 μM/l in human) using our strategy has been successfully demonstrated. In a model experiment using chromatography paper as a mimic of biological membrane, we have shown efficient degradation of the bilirubin under continuous monitoring for guidance of immediate/future course of action.

  8. Effect of syrepar and oxaphenamide on liver function in experimental hypokinesia

    NASA Technical Reports Server (NTRS)

    Skakun, L. N.

    1980-01-01

    Experiments on albino rats showed that 30 day hypokinesia changes the reaction of the liver to cholagogues. The choleretic action of oxaphenamide as well as its inhibitory effect on synthesis of bile acids diminishes, while the influence of bilirubin secretion increases.

  9. Does routine repeat testing of critical laboratory values improve their accuracy?

    PubMed Central

    Baradaran Motie, Pooya; Zare-Mirzaie, Ali; Shayanfar, Nasrin; Kadivar, Maryam

    2015-01-01

    Background: Routine repeat testing of critical laboratory values is very common these days to increase their accuracy and to avoid reporting false or infeasible results. We figure that repeat testing of critical laboratory values has any benefits or not. Methods: We examined 2233 repeated critical laboratory values in 13 different hematology and chemistry tests including: hemoglobin, white blood cell, platelet, international normalized ratio, partial thromboplastin time, glucose, potassium, sodium, phosphorus, magnesium, calcium, total bilirubin and direct bilirubin. The absolute difference and the percentage of change between the two tests for each critical value were calculated and then compared with the College of American Pathologists/Clinical Laboratory Improvement Amendments allowable error. Results: Repeat testing yielded results that were within the allowable error on 2213 of 2233 specimens (99.1%). There was only one outlier (0.2%) in the white blood cell test category, 9 (2.9%) in the platelet test category, 5 (4%) in the partial thromboplastin time test category, 5 (4.8%) in the international normalized ratio test category and none in other test categories. Conclusion: Routine, repeat testing of critical hemoglobin, white blood cell, platelet, international normalized ratio, partial thromboplastin time, glucose, potassium, sodium, phosphorus, magnesium, calcium, total bilirubin and direct bilirubin results does not have any benefits to increase their accuracy. PMID:26034729

  10. Bilhemia: A Rare Complication of Transjugular Intraheptic Portosytemic Shunt

    PubMed Central

    Zhang, Michael

    2015-01-01

    A 56-year-old woman with cirrhosis due to chronic hepatitis C underwent emergent transjugular intrahepatic portosystemic shunt (TIPS) due to a ruptured esophageal varix during esophagogastroduodenoscopy. Following TIPS, the patient experienced a rapid rise in serum bilirubin with no evidence of biliary obstruction or hepatic injury. She was determined to have bilhemia, a rare but serious complication of TIPS. PMID:26504882

  11. Isolation of an agent causing bilirubinemia and jaundice in raccoons

    USGS Publications Warehouse

    Kilham, L.; Herman, C.M.

    1954-01-01

    An infectious agent, which appears to be a virus (RJV) has been isolated from the liver of a wild raccoon which has led to a highly fatal type of disease characterized by conjunctivitis and an elevated serum bilirubin frequently accompanied by jaundice on inoculation of raccoons. Ferrets also appear to be susceptible to infections with this agent.

  12. Fetal Intrahepatic Cholestasis Secondary to BO Hemolytic Disease

    PubMed Central

    Raju, T. N. K.; Javed, Durr-I-Shahwar

    1981-01-01

    A rare occurrence of severe, direct hyperbilirubinemia in an infant with BO incompatibility was noted at four hours of age. Severe fetal hemolysis and markedly elevated indirect bilirubin levels might have caused induction of conjugating enzymes during fetal life in this case. Intrahepatic cholestasis was responsible for persistent conjugated hyperbilirubinemia after birth. This responded favorably to cholestyramine therapy. PMID:7196459

  13. Effects of Cholestasis on Learning and Locomotor Activity in Bile Duct Ligated Rats

    PubMed Central

    HOSSEINI, Nasrin; ALAEI, Hojjatallah; NASEHI, Mohammad; RADAHMADI, Maryam; Mohammad Reza, ZARRINDAST

    2014-01-01

    Background: Cognitive functions are impaired in patients with liver disease. Bile duct ligation causes cholestasis that impairs liver function. This study investigated the impact of cholestasis progression on the acquisition and retention times in the passive avoidance test and on the locomotor activity of rats. Methods: Cholestasis was induced in male Wistar rats by ligating the main bile duct. Locomotor activity, learning and memory were assessed by the passive avoidance learning test at day 7, day 14, and day 21 post-bile duct ligation. The serum levels of bilirubin, alanine aminotransferase, and alkaline phosphatase were measured. Results: The results showed that acquisition time and locomotor activity were not affected at day 7 and day 14, but they were significantly (P < 0.05) impaired at day 21 post-bile duct ligation compared with the results for the control group. Additionally, memory was significantly impaired on day 7 (P < 0.01), day 14, and day 21 (P < 0.001) compared with the control groups. The levels of total bilirubin, direct bilirubin, indirect bilirubin, alanine aminotransferase, and alkaline phosphatase were significantly higher at day 7, day 14, and day 21 post-bile duct ligation compared with the levels in the sham group. Conclusion: Based on these findings, both liver and memory function were affected in the early stage of cholestasis (7 days after bile duct ligation), while learning and locomotor activity were impaired at 21 days after bile duct ligation following the progression of cholestasis. PMID:24639608

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

    PubMed

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

    1983-05-01

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

  15. Case study 5. Deconvoluting hyperbilirubinemia: differentiating between hepatotoxicity and reversible inhibition of UGT1A1, MRP2, or OATP1B1 in drug development.

    PubMed

    Templeton, Ian; Eichenbaum, Gary; Sane, Rucha; Zhou, Jin

    2014-01-01

    New molecular entities (NMEs) are evaluated using a rigorous set of in vitro and in vivo studies to assess their safety and suitability for testing in humans. Regulatory health authorities require that therapeutic and supratherapeutic doses be administered, by the intended route of administration, to two nonclinical species prior to human testing (ICH Expert Working Group. The international conference on harmonization of technical requirements for registration of pharmaceuticals for human use (ICH); Multidisciplinary guidelines; Nonclinical safety studies (M3). http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Multidisciplinary/M3_R2/Step4/M3_R2__Guideline.pdf , 2009). The purpose of these studies is to identify potential target organ toxicity and to determine if the effects are reversible. Liver is a potential site for toxicity caused by orally administered NMEs due to high exposure during first pass after oral administration. A range of clinical chemistry analytes are routinely measured in both nonclinical and clinical studies to evaluate and monitor for hepatotoxicity. While bilirubin itself circulates within a wide range of concentrations in many animal species and humans, without causing adverse effects and possibly providing benefits (Sedlak and Snyder. Pediatrics 113(6):1776-1782, 2004), bilirubin is one of the few readily monitored circulating biomarkers that can provide insight into liver function. Therefore, any changes in plasma or urine bilirubin levels must be carefully evaluated. Changes in bilirubin may occur as a result of adaptive nontoxic changes or severe toxicity. Examples of adaptive nontoxic changes in liver function, which may elevate direct (conjugated) and/or indirect (unconjugated) bilirubin above baseline levels, include reversible inhibition of UGT1A1-mediated bilirubin metabolism and OATP1B1-, OATP1B3-, or MRP2-mediated transport (Keogh. Adv Pharmacol 63:1-42, 2012). Alternatively, hepatocellular necrosis

  16. Analysis of gastrointestinal and hepatic chronic GVHD manifestations on major outcomes: A Chronic GVHD Consortium study

    PubMed Central

    Pidala, Joseph; Chai, Xiaoyu; Kurland, Brenda F.; Inamoto, Yoshihiro; Flowers, Mary E.D.; Palmer, Jeanne; Khera, Nandita; Jagasia, Madan; Cutler, Corey; Arora, Mukta; Vogelsang, Georgia; Lee, Stephanie J.

    2013-01-01

    While data support adverse prognosis of overlap subtype of chronic GVHD, the importance of site of gastrointestinal (GI) and type of hepatic involvement is not known. Using data from the Chronic GVHD Consortium observational cohort study (n=567, total of 2115 visits), we examined whether the site of GI (esophageal, upper GI, lower GI) and type of hepatic (bilirubin, alkaline phosphatase (AP), alanine aminotransferase (ALT)) involvement are associated with overall survival (OS)and non-relapse mortality (NRM), symptoms, quality of life (QOL) and functional status measures. In multivariate analysis utilizing data from enrollment visits only, lower GI involvement (HR 1.67, p=0.05) and elevated bilirubin (HR 2.46, p=0.001) were associated with OS; both were also associated with NRM. In multivariable analysis using all visits (time-dependent covariates), GI score greater than zero (HR 1.69, p=0.02) and elevated bilirubin (HR 3.73, p<0.001) were associated with OS; results were similar for NRM. Any esophageal involvement and GI score greater than zero were associated with both symptoms and QOL while elevated bilirubin was associated with QOL. We found no consistent evidence that upper GI involvement, AP, ALT, or NIH liver score add prognostic value for survival, overall symptom burden, or quality of life. These data support important differences in patient-reported outcomes according to GI and hepatic involvement among chronic GVHD affected patients, and identify those with elevated bilirubin or higher GI score at any time, or lower GI involvement at cohort enrollment, as patients at greater risk for mortality under current treatment approaches. PMID:23395601

  17. Danning tablets attenuates α-naphthylisothiocyanate-induced cholestasis by modulating the expression of transporters and metabolic enzymes

    PubMed Central

    2014-01-01

    Background The Danning tablets (DNts) is commonly prescribed in China as a cholagogic formula. Our previous studies showed that DNts exerted the protective effect on α-naphthylisothiocyanate (ANIT)-induced liver injury with cholestasis in a dose-dependent mannar. However, the detailed molecular mechanisms of DNts against ANIT-induced cholestasis are still not fully explored. Methods Danning tablet (3 g/kg body weight/day) was administered orally to experimental rats for seven days before they were treated with ANIT (60 mg/kg daily via gastrogavage) which caused cholestasis. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin (T-Bil), direct bilirubin (D-Bil) and total bile acid (TBA) were measured to evaluate the protective effect of Danning tablet at 12, 24 and 48h after ANIT treatment. Meanwhile, total bilirubin or total bile acid in the bile, urine and liver were also measured at 48h after ANIT treatment. Furthermore, the hepatic or renal mRNA and protein levels of metabolic enzymes and transports were investigated to elucidate the protective mechanisms of Danning tablet against ANIT-induced cholestasis. Results In this study, we found that DNts significantly attenuated translocation of multidrug resistance-associated protein 2 (Mrp2) from the canalicular membrane into an intracellular and up-regulated the hepatic mRNA and protein expressions of metabolic enzymes including cytochrome P450 2b1(Cyp2b1) and uridine diphosphate-5¢- glucuronosyltransferase (Ugt1a1)) and transporters including bile salt export pump (Bsep) and multidrug resistance protein 2 (Mdr2)) as well as renal organic solute transporter beta (Ostβ), accompanied by further increase in urinary and biliary excretion of bile acid and bilirubin. Conclusions DNts might promote bile acid and bilirubin elimination by regulating the expressions of hepatic and renal transporters as well as hepatic metabolic enzymes. PMID:25033983

  18. Prediction of Severe Neonatal Hyperbilirubinemia Using Cord Blood Hydrogen Peroxide: A Prospective Study

    PubMed Central

    Chou, Hung-Chieh; Chien, Chiang-Ting; Tsao, Po-Nien; Hsieh, Wu-Shiun; Chen, Chien-Yi; Chang, Mei-Hwei

    2014-01-01

    Background We hypothesized that cord blood hydrogen peroxide (H2O2) could be utilized to predict the severity of neonatal hyperbilirubinemia. Methods We prospectively enrolled term or near-term healthy neonates. Cord blood and capillary blood at three days of age were measured for hydrogen peroxide and bilirubin concentrations. For newborns with hyperbilirubinemia, further blood samples were obtained at five and seven days of age. Newborns were divided into severe or less severe hyperbilirubinemic groups (peak bilirubin ≥17 mg/dL or not). The sensitivity, specificity, and negative predictive values were determined. Results There were 158 neonates enrolled. The incidence of neonatal hyperbilirubinemia was 30.5% for a concentration ≥15 mg/dl. The rising patterns were similar among bilirubin concentrations and hydrogen peroxide levels during the first few days of life. There was a strong positive correlation between bilirubin concentrations and hydrogen peroxide levels after correlation analysis. The rate of severe hyperbilirubinemia was 13.3%. It revealed that a cord blood hydrogen peroxide signal level of 2500 counts/10 seconds was an appropriate cut-off for predicting severe hyperbilirubinemia. Sensitivity and the negative predictive value were 76.2% and 93.3%, respectively. Conclusions Our findings confirm that hydrogen peroxide levels and bilirubin concentrations in cord and neonatal blood are closely related. A cord blood hydrogen peroxide level above 2500 counts/10 seconds associated with a high predictive value for severe hyperbilirubinemia. This method provides information about which neonate should be closely followed after discharge from the nursery. PMID:24466244

  19. Systemic effects of orally-administered zinc and tin (IV) metalloporphyrins on heme oxygenase expression in mice.

    PubMed

    Morioka, Ichiro; Wong, Ronald J; Abate, Aida; Vreman, Hendrik J; Contag, Christopher H; Stevenson, David K

    2006-05-01

    Some metalloporphyrins (Mps) inhibit heme oxygenase (HO), the rate-limiting enzyme in the production of bilirubin, and are potential compounds for the treatment of neonatal jaundice. We studied the safety and efficacy of Mps following oral administration. Adult HO-1-luc reporter mice were administered 30 micromol/kg body weight of tin mesoporphyrin (SnMP), zinc bis glycol deuteroporphyrin (ZnBG), or zinc protoporphyrin (ZnPP), or vehicle by oral gavage. Bilirubin production was measured as total body carbon monoxide (CO) excretion (VeCO). HO activity was quantitated via CO measurements by gas chromatography. HO-1 protein was determined by Western blot. HO-1 transcription levels were assessed by in vivo bioluminescence imaging. A significant 28% decrease in bilirubin production occurred within 3 h of SnMP treatment and persisted beyond 48 h. Bilirubin production decreased 15% and 9% by 3 h after administration of ZnBG and ZnPP, respectively, but returned to baseline within 48 h. Maximal inhibition of liver, spleen, and intestine HO activity was seen at 3 h with inhibitory effects decreasing in the order: SnMP > or = ZnBG > or = ZnPP. After SnMP treatment, HO-1 transcription increased 5.7-fold after 24 h. Furthermore, liver and spleen HO-1 protein significantly increased 3.7- and 2.0-fold, respectively, after 24 h. HO-1 transcription and protein were not affected in ZnBG- or ZnPP-treated mice. We conclude that the three Mps are absorbed at different rates in the mouse and affect bilirubin production and HO-1 expression in a tissue- and time-dependent manner. PMID:16627879

  20. Screening for UGT1A1 Genotype in Study A5257 Would Have Markedly Reduced Premature Discontinuation of Atazanavir for Hyperbilirubinemia

    PubMed Central

    Vardhanabhuti, Saran; Ribaudo, Heather J.; Landovitz, Raphael J.; Ofotokun, Ighovwerha; Lennox, Jeffrey L.; Currier, Judith S.; Olson, Lana M.; Haas, David W.

    2015-01-01

    Background. Some patients are not prescribed atazanavir because of concern about possible jaundice. Atazanavir-associated hyperbilirubinemia correlates with UGT1A1 rs887829 genotype. We examined bilirubin-related discontinuation of atazanavir in participants from AIDS Clinical Trials Group Study A5257. Methods. Discriminatory properties of UGT1A1 T/T genotype for predicting bilirubin-related atazanavir discontinuation through 96 weeks after antiretroviral initiation were estimated. Results. Genetic analyses involved 1450 participants, including 481 who initiated randomized atazanavir/ritonavir. Positive predictive values of rs887829 T/T for bilirubin-related discontinuation of atazanavir (with 95% confidence intervals [CIs]) were 20% (CI, 9%–36%) in Black, 60% (CI, 32%–84%) in White, and 29% (CI, 8%–58%) in Hispanic participants; negative predictive values were 97% (CI, 93%–99%), 95% (CI, 90%–98%), and 97% (CI, 90%–100%), respectively. Conclusions. Bilirubin-related discontinuation of atazanavir was rare in participants not homozygous for rs887829 T/T, regardless of race or ethnicity. We hypothesize that the higher rate of discontinuation among White participants homozygous for rs887829 T/T may reflect differences in physical manifestations of jaundice by race and ethnicity. Selective avoidance of atazanavir initiation among individuals with T/T genotypes would markedly reduce the likelihood of bilirubin-related discontinuation of atazanavir while allowing atazanavir to be prescribed to the majority of individuals. This genetic association will also affect atazanavir/cobicistat. PMID:26180834

  1. Hyperbilirubinemia exaggerates endotoxin-induced hypothermia

    PubMed Central

    Pakai, Eszter; Garami, Andras; Nucci, Tatiane B; Ivanov, Andrei I; Romanovsky, Andrej A

    2015-01-01

    Systemic inflammation is accompanied by an increased production of reactive oxygen species (ROS) and by either fever or hypothermia (or both). To study aseptic systemic inflammation, it is often induced in rats by the intravenous administration of bacterial lipopolysaccharide (LPS). Knowing that bilirubin is a potent ROS scavenger, we compared responses to LPS between normobilirubinemic Gunn rats (heterozygous, asymptomatic; J/+) and hyperbilirubinemic Gunn rats (homozygous, jaundiced; J/J) to establish whether ROS mediate fever and hypothermia in aseptic systemic inflammation. These two genotypes correspond to undisturbed versus drastically suppressed (by bilirubin) tissue accumulation of ROS, respectively. A low dose of LPS (10 μg/kg) caused a typical triphasic fever in both genotypes, without any intergenotype differences. A high dose of LPS (1,000 μg/kg) caused a complex response consisting of early hypothermia followed by late fever. The hypothermic response was markedly exaggerated, whereas the subsequent fever response was strongly attenuated in J/J rats, as compared to J/+ rats. J/J rats also tended to respond to 1,000 μg/kg with blunted surges in plasma levels of all hepatic enzymes studied (alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase), thus suggesting an attenuation of hepatic damage. We propose that the reported exaggeration of LPS-induced hypothermia in J/J rats occurs via direct inhibition of nonshivering thermogenesis by bilirubin and possibly via a direct vasodilatatory action of bilirubin in the skin. This hypothermia-exaggerating effect might be responsible, at least in part, for the observed tendency of J/J rats to be protected from LPS-induced hepatic damage. The attenuation of the fever response to 1,000 μg/kg could be due to either direct actions of bilirubin on thermoeffectors or the ROS-scavenging action of bilirubin. However, the experiments with 10 μg/kg strongly suggest that ROS signaling is

  2. Hyperbilirubinemia exaggerates endotoxin-induced hypothermia.

    PubMed

    Pakai, Eszter; Garami, Andras; Nucci, Tatiane B; Ivanov, Andrei I; Romanovsky, Andrej A

    2015-01-01

    Systemic inflammation is accompanied by an increased production of reactive oxygen species (ROS) and by either fever or hypothermia (or both). To study aseptic systemic inflammation, it is often induced in rats by the intravenous administration of bacterial lipopolysaccharide (LPS). Knowing that bilirubin is a potent ROS scavenger, we compared responses to LPS between normobilirubinemic Gunn rats (heterozygous, asymptomatic; J/+) and hyperbilirubinemic Gunn rats (homozygous, jaundiced; J/J) to establish whether ROS mediate fever and hypothermia in aseptic systemic inflammation. These two genotypes correspond to undisturbed versus drastically suppressed (by bilirubin) tissue accumulation of ROS, respectively. A low dose of LPS (10 μg/kg) caused a typical triphasic fever in both genotypes, without any intergenotype differences. A high dose of LPS (1,000 μg/kg) caused a complex response consisting of early hypothermia followed by late fever. The hypothermic response was markedly exaggerated, whereas the subsequent fever response was strongly attenuated in J/J rats, as compared to J/+ rats. J/J rats also tended to respond to 1,000 μg/kg with blunted surges in plasma levels of all hepatic enzymes studied (alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase), thus suggesting an attenuation of hepatic damage. We propose that the reported exaggeration of LPS-induced hypothermia in J/J rats occurs via direct inhibition of nonshivering thermogenesis by bilirubin and possibly via a direct vasodilatatory action of bilirubin in the skin. This hypothermia-exaggerating effect might be responsible, at least in part, for the observed tendency of J/J rats to be protected from LPS-induced hepatic damage. The attenuation of the fever response to 1,000 μg/kg could be due to either direct actions of bilirubin on thermoeffectors or the ROS-scavenging action of bilirubin. However, the experiments with 10 μg/kg strongly suggest that ROS signaling is not

  3. AB161. High resolution melting analysis of buccal DNA revealed a significant association between UGT1A1 c.211G>A and neonatal hyperbilirubinemia development in Malay population

    PubMed Central

    Cheung, Tian Pei; Van Rostenberghe, Hans; Ismail, Rosliza; Nawawi, Noor Namirah; Abdullah, Nurul Amierah; Ramli, Noraida; Ibrahim, Nor Rosidah; Hj Abd Majid, Noorizan; Mohd Yusoff, Narazah; Nishio, Hisahide; Yusoff, Surini

    2015-01-01

    Background Severe neonatal hyperbilirubinemia or neonatal jaundice (NNJ) characterised by an elevated total serum bilirubin (TSB) level may result in kernicterus or even death. Uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) is the key enzyme which conjugates bilirubin with glucuronic acid for the subsequent bilirubin excretion. Conversely, constitutive androstane receptor (CAR), encoded by nuclear receptor subfamily 1, group I, member 3 (NR1I3) gene, regulates bilirubin excretion by activating the components of the bilirubin clearance pathway. Thus, genetic variants in UGT1A1 and NR1I3 genes may modulate bilirubin excretion and lead to NNJ. This study aimed to determine the association between UGT1A1 and NR1I3 genetic variants and NNJ development in Malay population by genotyping the DNA isolated from buccal swabs. The accuracy and reliability of the genotyping results produced by buccal DNA was also compared with that of the whole blood DNA. Methods Buccal swabs were collected from 232 hyperbilirubinemia and 232 non-hyperbilirubinemia newborns admitted to and/or born in Hospital Universiti Sains Malaysia (HUSM). Hyperbilirubinemia subjects were those with TSB levels ≥250 µmol/L within the first week after birth while non-hyperbilirubinemia subjects were newborns without significant hyperbilirubinemia. The UGT1A1 (c.211G>A) and NR1I3 [MPJ6_1I3008 (G>A), IVS8+116T>G and 540A>G] variants were genotyped by using high resolution melting (HRM) analysis. Binary logistic regression was used to assess the association between variant genotypes and risk of NNJ. Whole blood samples were also collected from 60 subjects and genotyped to compare the HRM genotyping results with that of the buccal swabs. Results When compared with wild-type genotype, both heterozygous and homozygous variant genotypes of MPJ6_1I3008 (G>A), IVS8+116T>G and 540A>G were not significantly associated with NNJ. However, the heterozygous genotype (GA) of c.211G>A was found to increase the

  4. The Possible Efficacy of Artichoke in Fluconazole Related Hepatotoxicity

    PubMed Central

    Toprak, Omer

    2014-01-01

    Although fluconazole related hepatotoxicity (FRH) is rare, mortal acute hepatic necrosis and jaundice were reported in immunocompromised states such as acquired immunodeficiency syndrome (AIDS) and bone marrow transplant (BMT). We present a case of a patient with multiple sclerosis who developed hepatotoxicity with the use of a single 150 mg fluconazole tablet for fungal vaginitis, 10 days after methylprednisolone pulse treatment. Our patient's alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were decreased, 1200 U/L and 800 U/L, respectively, and bilirubin levels were consistent at 37 mg/dL. Artichoke which has anticholestatic and antioxidant properties was used by our patient. She consumed a 30 mg artichoke leaf extract tea 3 times a day. The bilirubin levels significantly declined at the end of the first week and all liver function tests were normalized within 2 months. PMID:25374729

  5. Green pigmentation in human teeth. A stereomicroscopic study.

    PubMed

    Rakauskaite, Asta; Juodzbalys, Gintaras; Pauza, Dainius H; Cicciù, Marco

    2014-01-01

    Green pigmentation in teeth is an uncommon condition associated with bilirubin deposits in hard dental tissues. Its occurrence can cause anxiety to both the child and parents and is not diagnosed easily by clinicians. The aim of this study is to analyze the current knowledge about the etiology, the intraoral alterations, and the macroscopic and microscopic features of green teeth pigmentation related to a high bilirubin levels. A primary tooth was extracted and manually sliced into 600 microns thin sections. The slenderized slices were examined with a light microscope AxioImager M1 to evaluate the microscopic teeth structure. The clinical characteristics of teeth may help in the diagnosis of current or past systemic diseases. Pediatricians should be able to quickly note the signs in order to perform the proper diagnosis. This study may help clinicians gain more knowledge about the current status of this uncommon pathology. PMID:25571689

  6. Actinomyces naeslundii and Eikenella corrodens as rare causes of liver abscesses.

    PubMed

    Jaqua, Nathan Thomas; Smith, Adam J; Shin, Terry T; Jahanmir, Jay

    2013-01-01

    A 48-year-old man with an unremarkable medical history was admitted with vague conditions of fever, chills, myalgias and malaise. Physical examination was remarkable for only scleral icterus. Laboratory evaluation revealed elevated aminotransferases, alkaline phosphatase and bilirubin. Imaging demonstrated two masses in the right lobe of his liver, which were ultimately drained and cultures demonstrated Actinomyces and Eikenella. He continued to have fever on broad-spectrum antibiotics until catheter drainage of the abscesses was performed. He was eventually discharged in improved condition on amoxicillin-clavulanate. His aminotransferases, alkaline phosphatase and bilirubin continued to improve and he remained afebrile and asymptomatic. A repeat CT 2 months after discharge demonstrated resolution of the abscesses. Actinomyces and Eikenella are rare causes of liver abscesses and treatment requires drainage and an extended course of antibiotics. The polymicrobial character typical of liver abscesses makes antibiotic therapy challenging when cultures reveal rare organisms such as Actinomyces and Eikenella. PMID:23867879

  7. Management of pregnancy in Crigler Najjar syndrome type 2

    PubMed Central

    Chaubal, Alisha Nitin; Patel, Ruchir; Choksi, Dhaval; Shah, Kaivan; Ingle, Meghraj; Sawant, Prabha

    2016-01-01

    Crigler Najjar syndrome is associated with indirect hyperbilirubinemia due to a deficiency of enzyme Uridine Di Phospho Glucoronosyl Transferase (UDPGT). Presented here is a case of a female in the first trimester of pregnancy, who was diagnosed to have type 2 Crigler Najjar syndrome. We also discuss the management of this rare disease especially in pregnancy. Unconjugated bilirubin can cross the placental barrier causing neurological damage in the newborn. Patient was carefully monitored during pregnancy and treatment with phenobarbitone in low doses was adjusted such that the serum bilirubin levels were below 10 mg/dL. Crigler Najjar syndrome being rare needs to be diagnosed early in pregnancy to avoid adverse fetal outcomes. Phenobarbitone being an inducer of enzyme UDPGT is used as the first line of treatment and is not teratogenic in the low doses used. Treatment protocol followed was on the basis of previous reported cases and successful perinatal outcome was achieved. PMID:27099654

  8. When less is more: a case of phenytoin toxicity

    PubMed Central

    Robertson, Kit; von Stempel, Conrad Brice; Arnold, Ian

    2013-01-01

    The authors present a case of an 87-year-old gentleman who presented with general deterioration, increased confusion, recurrent falls and unsteadiness. He was treated for a urinary tract infection but was found to deteriorate rapidly, developing bilateral nystagmus, marked pastpointing, dysarthria and central ataxia. He had a complex medical history including epilepsy controlled with long-term phenytoin. Phenytoin is 90% protein bound and displaced by bilirubin. At the time of deterioration his total phenytoin concentration was within the limits of the laboratory's recommended therapeutic range. The biochemistry report also denoted the patient was hypoalbuminaemic and hyperbilirubinaemic. His symptoms completely resolved with phenytoin dose reduction. The combination of low albumin and high bilirubin may cause an increase in the free phenytoin concentration, resulting in toxicity, despite the measured total phenytoin concentration being within the therapeutic interval. PMID:23536644

  9. Effect of road transportation on the serum biochemical parameters of cynomolgus monkeys and beagle dogs

    PubMed Central

    OCHI, Takehiro; YAMADA, Azusa; NAGANUMA, Yuki; NISHINA, Noriko; KOYAMA, Hironari

    2016-01-01

    To determine the effect of long-distance (approximately 600 km) road transportation on the blood biochemistry of laboratory animals, we investigated the changes in serum biochemical parameters in healthy cynomolgus monkeys and beagle dogs transported by truck from Osaka to Tsukuba, Japan. The concentrations of serum cortisol, total bilirubin and aspartate aminotransferase in monkeys increased during transportation. Serum cortisol and total bilirubin levels in dogs also increased during transportation, but serum triglyceride decreased. Serum parameter values in truck-transported monkeys and dogs returned to baseline levels within two weeks following arrival. Taken together, these results suggest that a two-week acclimation period is the minimum duration required for adaptation following road transportation. PMID:26833142

  10. [Treatment of neonatal hyperbilirubinemia

    PubMed

    Carvalho, M D

    2001-07-01

    OBJECTIVE: To review the recent medical literature on the treatment of neonatal jaundice, focusing on practical aspects that are relevant to pediatricians and neonatologists. SOURCES: An extensive review of the related literature was performed, also including the authors clinical experience in this field of investigation. SUMMARY OF THE FINDINGS: Jaundice is very common among infants during the first days of life. Several factors such as maternal and neonatal history have to be considered before implementing treatment. Significant advances have been made in the past few years concerning the treatment of jaundiced newborn infants. This review focuses on three forms of treatment of neonatal hyperbilirubinemia: phototherapy, exchange transfusion and the use of drugs to reduce serum bilirubin concentration. CONCLUSIONS: Nowadays, the in-depth knowledge about the mechanism of action of phototherapy, the development of intensified phototherapy units and the use of drugs to reduce bilirubin formation, have contributed to significantly decrease the need for exchange transfusion. PMID:14676895

  11. Hyperbilirubinemia: new approaches to an old problem.

    PubMed

    Schwoebel, A; Sakraida, S

    1997-12-01

    Hyperbilirubinemia continues to be a common problem of the term and near-term neonate. Each year more than 60% of infants born in the United States develop jaundice, making it difficult at times to differentiate jaundice due to pathologic reasons from jaundice due to physiologic ones. Now, the knowledge that bilirubin may even have a beneficial role as an antioxidant has caused a great deal of renewed interest in the management of jaundice. The American Academy of Pediatrics has published revised guidelines for management of neonatal jaundice that have resulted in much discussion. The article reviews current theories of bilirubin production and clearance, noninvasive and nonintrusive techniques to assess and care for jaundice, and newer concepts of preventive and treatment modalities from a nursing perspective. PMID:9451194

  12. Kernicterus in sick and preterm infants (1999-2002): a need for an effective preventive approach.

    PubMed

    Bhutani, Vinod K; Johnson, Lois H; Shapiro, Steven M

    2004-10-01

    Kernicterus in sick and preterm infants is a rarity. Universal availability of phototherapy and concerted clinical efforts to identify, effectively manage and establish clinical guidelines have been instrumental in preventing kernicterus in US intensive care nurseries. However, in sick and preterm infants the absence of precise data on prevalence of bilirubin induced neurologic injury, the lack of proven predictive indices and the absence of evidence-based studies that clearly demonstrate the actual risk of kernicterus. These leave questions regarding the basis for clinical strategies and recommendations for the management of neonatal jaundice in this select population. This article reviews 6 preterm infants selected from the Pilot Kernicterus Registry who had recovered from life-threatening neonatal illnesses, briefly discusses current indices used to ascertain risk, and offers an initial bilirubin level based identification of infants while future directions and studies are conducted to supplement our presently incomplete knowledge for safer clinical practice. PMID:15686262

  13. Icterus Neonatorum in Near-Term and Term Infants

    PubMed Central

    Ali, Rehan; Ahmed, Shakeel; Qadir, Maqbool; Ahmad, Khalil

    2012-01-01

    Neonatal jaundice is the yellowish discoloration of the skin and/or sclerae of newborn infants caused by tissue deposition of bilirubin. Physiological jaundice is mild, unconjugated (indirect-reacting) bilirubinaemia, and affects nearly all newborns. Physiological jaundice levels typically peak at 5 to 6 mg/dL (86 to 103 μmol/L) at 72 to 96 hours of age, and do not exceed 17 to 18 mg/dL (291–308 μmol/L). Levels may not peak until seven days of age in Asian infants, or in infants born at 35 to 37 weeks’ gestation. Higher levels of unconjugated hyperbilirubinaemia are considered pathological and occur in a variety of conditions. The clinical features and management of unconjugated hyperbilirubinaemia in healthy near-term and term infants, as well as bilirubin toxicity and the prevention of kernicterus, are reviewed here. The pathogenesis and aetiology of this disorder are discussed separately. PMID:22548133

  14. Diagnosis of acute cholecystitis using hepatobiliary scan with technetium-99m PIPIDA

    SciTech Connect

    Bennett, M.T.; Sheldon, M.I.; dos Remedios, L.V.; Weber, P.M.

    1981-09-01

    Sixty patients were evaluated for acute abdominal pain using technetium-99m PIPIDA hepatobiliary imaging. The sensitivity of the test was 90.6 percent in all patients and the accuracy was 93.3 percent. In the evaluation of acutely ill patients with right upper quadrant pain, fever, nausea and vomiting, hepatobiliary imaging with PIPIDA is the preferred test for diagnosing acute cholecystitis. If the test is positive, disease of the gallbladder and probably acute cholecystitis are present. Early operation can proceed if desirable. If the test is negative and the bilirubin level is less than 5.0 mg/dl, acute cholecystitis is not present. In such cases conservative treatment is appropriate, and follow-up tests should be performed to evaluate the possibility of chronic cholecystitis. When the bilirubin level exceeds 5.0 mg/dl, the test is often indeterminate.

  15. Bile cast nephropathy: A case report and review of the literature

    PubMed Central

    Patel, Jaymon; Walayat, Saqib; Kalva, Nikhil; Palmer-Hill, Sidney; Dhillon, Sonu

    2016-01-01

    Bile cast nephropathy is a condition of renal dysfunction in the setting of hyperbilirubinemia. There are very few cases of this condition reported in the last decade and a lack of established treatment guidelines. While the exact etiology remains unknown, bile cast nephropathy is presumed to be secondary to multiple concurrent insults to the kidney including direct toxicity from bile acids, obstructive physiology from bile casts, and systemic hypoperfusion from vasodilation. Therapy directed at bilirubin reduction may improve renal function, but will likely need dialysis or plasmapheresis as well. We report our case of bile cast nephropathy and the therapeutic measures undertaken in a middle-aged male with chronic renal insufficiency that developed hyperbilirubinemia and drug-induced liver injury secondary to antibiotic use. He developed acute renal injury in the setting of rising bilirubin. He subsequently had a progressive decline in renal and hepatic function, requiring dialysis and plasmapheresis with some improvement, ultimately requiring transplantation. PMID:27468221

  16. Development and operation of gold and cobalt oxide nanoparticles containing polypropylene based enzymatic fuel cell for renewable fuels.

    PubMed

    Kilic, Muhammet Samet; Korkut, Seyda; Hazer, Baki; Erhan, Elif

    2014-11-15

    Newly synthesized gold and cobalt oxide nanoparticle embedded Polypropylene-g-Polyethylene glycol was used for a compartment-less enzymatic fuel cell. Glucose oxidase and bilirubin oxidase were selected as anodic and cathodic enzymes, respectively. Electrode fabrication and EFC operation parameters were optimized to achieve high power output. Maximum power density of 23.5 µW cm(-2) was generated at a cell voltage of +560 mV vs Ag/AgCl, in 100mM PBS pH 7.4 with the addition of 20mM of synthetic glucose solution. 20 µg of polymer amount with 185 µg of glucose oxidase and 356 µg of bilirubin oxidase was sufficient to get maximum performance. The working electrodes could harvest glucose, produced during photosynthesis reaction of Carpobrotus Acinaciformis plant, and readily found in real domestic wastewater of Zonguldak City in Turkey. PMID:24951919

  17. Protective effects of Capparis sepiaria root extracts against acetaminophen-induced hepatotoxicity in Wistar rats.

    PubMed

    Madhavan, V; Pandey, Ajay Shankar; Murali, Anita; Yoganarasimhan, S N

    2012-01-01

    Capparis sepiaria L. known as Himsra is an important drug in Ayurveda. In this study extracts of the root of C. sepiaria were evaluated for their hepatoprotective potential on acetaminophen-induced hepatotoxicity in albino Wistar rats. The extent of hepatoprotection was evaluated by estimating the serum levels of hepatic transaminases (SGPT and SGOT), alkaline phosphatase (ALP), total protein (TP), and bilirubin (total and direct). Aqueous and ethanol extracts of C. sepiaria significantly reduced the increased liver weight as well as serum levels of SGPT, SGOT, ALP, and bilirubin, and normalized the reduced serum protein levels in the treated rats. These observations were supported by the results of histopathology studies as well. The extracts were also subjected to preliminary organic analysis and chromatographic studies including HPTLC finger print studies. The results indicate that the roots of C. sepiaria show significant hepatoprotective effect on acetaminophen-induced hepatotoxicity, thus substantiating its use as a potential hepatoprotective drug. PMID:22718675

  18. Successful operation for mitral regurgitation in a patient with Gilbert's syndrome.

    PubMed

    Minami, Hiroya; Asada, Tatsuro; Gan, Kunio; Yamada, Akitoshi; Yano, Yoshihiko

    2011-05-01

    A 72-year-old woman complaining of dyspnea on effort was diagnosed as having mitral regurgitation (MR). Asymptomatic jaundice had initially been noticed during primary school, and an examination had shown hyperbilirubinemia. After the diagnosis of constitutional jaundice, she had remained well without further examination or medical treatment. Laboratory data showed a total serum bilirubin (TB) level of 12.2 mg/dl and a direct bilirubin level of 0.6 mg/dl. Transesophageal echocardiography showed severe MR, and we replaced the mitral valve. Postoperatively, genetic analyses identified constitutional jaundice as Gilbert's syndrome with Y486D mutation. The TB level gradually decreased. Four years after operation she is doing well with moderate hyperbilirubinemia and a TB level of 5 mg/dl. She is free from heart failure. PMID:21547629

  19. Bile cast nephropathy: A case report and review of the literature.

    PubMed

    Patel, Jaymon; Walayat, Saqib; Kalva, Nikhil; Palmer-Hill, Sidney; Dhillon, Sonu

    2016-07-21

    Bile cast nephropathy is a condition of renal dysfunction in the setting of hyperbilirubinemia. There are very few cases of this condition reported in the last decade and a lack of established treatment guidelines. While the exact etiology remains unknown, bile cast nephropathy is presumed to be secondary to multiple concurrent insults to the kidney including direct toxicity from bile acids, obstructive physiology from bile casts, and systemic hypoperfusion from vasodilation. Therapy directed at bilirubin reduction may improve renal function, but will likely need dialysis or plasmapheresis as well. We report our case of bile cast nephropathy and the therapeutic measures undertaken in a middle-aged male with chronic renal insufficiency that developed hyperbilirubinemia and drug-induced liver injury secondary to antibiotic use. He developed acute renal injury in the setting of rising bilirubin. He subsequently had a progressive decline in renal and hepatic function, requiring dialysis and plasmapheresis with some improvement, ultimately requiring transplantation. PMID:27468221

  20. Descriptive urological record of chimpanzees (Pan troglodytes) in the wild and limitations associated with using multi-reagent dipstick test strips.

    PubMed

    Kaur, Taranjit; Huffman, Michael A

    2004-08-01

    Ten urine chemistry parameters were measured on 74 voided urine samples from 34 wild chimpanzees (Pan troglodytes). Multi-reagent urine dipstick tests were performed and results determined using colorimetric scales. Urine pH measured between 8 and 9 units in 91% of the chimpanzees. Test pads detected protein, erythrocytes, leukocyte esterase activity, and nitrites, ketones and bilirubin in 47, 32, 29, and <10% of the chimpanzees, respectively. No apparent association between positive test results for blood in adult females and reproductive status was found. Overall, 17 of the 34 chimpanzees had positive urine test results for protein, hemoglobin, erythrocytes, leukocytes, nitrites, ketones, and/or bilirubin. Dipstick urinalysis alone is an unreliable method for assessing health and physiological status of wild chimpanzees. However, if combined with other diagnostics it could prove to be a valuable health-monitoring tool. Limitations associated with this methodology need to be considered when interpreting urinary dipstick test results. PMID:15271068

  1. Homorubins and Homoverdins

    PubMed Central

    Pfeiffer, William P.; Dey, Sanjeev K.; Falk, Heinz

    2014-01-01

    The syntheses are described for centrally expanded bilirubin analogs: b-homorubins with propionic and butyric acid groups in the positions corresponding to the propionic acids of bilirubin. Their syntheses were accomplished by coupling two equivalents of a reactive monopyrrole (5-(bromomethylene)pyrrolin-2-one) to a dipyrrylethane. The corresponding b-homoverdins and dehydro-b-homoverdins were prepared by dehydrogenating the rubins or their dimethyl esters using DDQ. As supported by NMR measurements and molecular mechanics calculations, the homorubins are found to engage in conformation-determining intramolecular hydrogen bonding between the dipyrrinone and carboxylic acid moieties. Likewise, the homoverdins are believed to favor intramolecularly hydrogen-bonded conformations. PMID:25110360

  2. Clinicopathological evaluation of downer dairy cows with fatty liver

    PubMed Central

    Kalaitzakis, Emmanouil; Panousis, Nikolaos; Roubies, Nikolaos; Giadinis, Nektarios; Kaldrymidou, Eleni; Georgiadis, Marios; Karatzias, Harilaos

    2010-01-01

    This study evaluated the relationship between severity of fatty liver and macromineral status in downer dairy cows and determined the usefulness of selected biochemical analytes for assessing prognosis. Blood and liver biopsy specimens were obtained from 36 Holstein downer cows shortly after the cows became recumbent and before they were treated. Liver tissue was examined histologically and serum activity of liver-derived enzymes and concentration of total lipids, triglycerides, bile acids, glucose, β-hydroxybutyrate, acetoacetic acid, total bilirubin, non-esterified fatty acids (NEFA), cholesterol and macrominerals (Ca, Mg, K, Na, P) were determined. Fatty liver infiltration was severe in 44% of the cows and moderate in 44%. Serum activities of ornithine carbamoyltransferase and glutamate dehydrogenase, and NEFA/cholesterol ratio were good indicators of fatty liver. Cows with severe fatty liver had the lowest mean K values. The prognosis is guarded for downer cows with moderate and severe fatty liver and when total bilirubin concentration is high. PMID:20808573

  3. Operational use of neem oil as an alternative anopheline larvicide. Part B: Environmental impact and toxicological potential.

    PubMed

    Awad, O M

    2003-07-01

    This study was conducted to investigate the preliminary environmental and mammalian toxicology of neem oil, temephos and chlorpyriphos-methyl/fenitrothion. Culex pipiens, Daphnia magna and Gambusia affinis were used to study environmental impact. A high level of toxicity was observed, with slight differences between organisms. The emulsifiers individually also displayed toxicity towards the tested organisms. Up to 90 days daily oral crude neem oil treatment (5 g/kg body weight) of laboratory mice did not cause any significant changes in weekly body weight gain, nor in serum liver damage indicators, direct bilirubin or total bilirubin. Blood parameters of treated mice up to 90 days were not statistically different from those of control mice. Neem oil could be used as an environmentally friendly alternative to the traditional chemical anopheline larvicides. PMID:15748062

  4. Antihepatotoxic effect of golden berry (Physalis peruviana Linn.) in carbon tetrachloride (CCl4) intoxicated rats.

    PubMed

    Taj, Darakhshan; Khan, Hira; Sultana, Viqar; Ara, Jehan; Ehteshamul-Haque, Syed

    2014-05-01

    Liver is the main site in the body for intense metabolism and excretion. A number of chemicals and drugs which are used routinely cause liver damage. The present study investigates the antihepatotoxic effect of Physalis peruviana whole ripe fruit, water and ethanol extracts of fruit in normal as well as in carbon tetrachloride (CCl(4)) intoxicated rats. The CCl(4) treated rats showed marked elevation in liver enzymes: alanine transaminse, aspratate transaminase, alkaline phosphatase, lactate dehydrogenase and other biochemical parameters: bilirubin, creatinine and urea, thus indicating liver injury. Whereas animal treated/fed with various preparations of Physalis peruviana showed significant lowering effect (p<0.05) in the elevated levels of serum markers like ALAT, ASAT, ALP, LDH, creatinine, urea and bilirubin indicating the protection against hepatic cell damage. The water extract of Physalis peruviana showed highest activity in both rat models while ripe fruit and ethanol extract showed moderate activity compared to standard drug. PMID:24811807

  5. Molecular analysis of patients of Sardinian descent with Crigler-Najjar syndrome type I.

    PubMed Central

    Rosatelli, M C; Meloni, A; Faa, V; Saba, L; Crisponi, G; Clemente, M G; Meloni, G; Piga, M T; Cao, A

    1997-01-01

    This study reports the molecular characterisation of the bilirubin UDP-glucuronosyl-transferase gene (UGT1) in a group of patients of Sardinian descent with Crigler-Najjar syndrome type I and their relatives. Sequence analysis of both UGT1A exon 1 and common exons 2-5 was performed in all patients, leading to the detection of AF170 and a novel mutation (470insT), both residing in UGT1A exon 1. All but two heterozygotes for the AF170 mutation showed normal serum bilirubin levels. These two subjects were also heterozygous for the sequence variation A(TA)7TAA in the promoter region of the UGT1A gene. Images PMID:9039987

  6. Possible involvement of PPARγ-associated eNOS signaling activation in rosuvastatin-mediated prevention of nicotine-induced experimental vascular endothelial abnormalities.

    PubMed

    Kathuria, Sonam; Mahadevan, Nanjaian; Balakumar, Pitchai

    2013-02-01

    Nicotine exposure via cigarette smoking and tobacco chewing is associated with vascular complications. The present study investigated the effect of rosuvastatin in nicotine (2 mg/kg/day, i.p., 4 weeks)-induced vascular endothelial dysfunction (VED) in rats. The development of VED was assessed by employing isolated aortic ring preparation and estimating aortic and serum nitrite/nitrate concentration. Further, scanning electron microscopy and hematoxylin-eosin staining of thoracic aorta were performed to assess the vascular endothelial integrity. Moreover, oxidative stress was assessed by estimating aortic superoxide anion generation and serum thiobarbituric acid-reactive substances. The nicotine administration produced VED by markedly reducing acetylcholine-induced endothelium-dependent relaxation, impairing the integrity of vascular endothelium, decreasing aortic and serum nitrite/nitrate concentration, increasing oxidative stress, and inducing lipid alteration. However, treatment with rosuvastatin (10 mg/kg/day, i.p., 4 weeks) markedly attenuated nicotine-induced vascular endothelial abnormalities, oxidative stress, and lipid alteration. Interestingly, the co-administration of peroxisome proliferator-activated receptor γ (PPARγ) antagonist, GW9662 (1 mg/kg/day, i.p., 2 weeks) submaximally, significantly prevented rosuvastatin-induced improvement in vascular endothelial integrity, endothelium-dependent relaxation, and nitrite/nitrate concentration in rats administered nicotine. However, GW9662 co-administration did not affect rosuvastatin-associated vascular anti-oxidant and lipid-lowering effects. The incubation of aortic ring, isolated from rosuvastatin-treated nicotine-administered rats, with L-NAME (100 μM), an inhibitor of nitric oxide synthase (NOS), significantly attenuated rosuvastatin-induced improvement in acetylcholine-induced endothelium-dependent relaxation. Rosuvastatin prevents nicotine-induced vascular endothelial abnormalities by activating

  7. Usefulness of visceral obesity (waist/hip ratio) in predicting vascular endothelial function in healthy overweight adults.

    PubMed

    Brook, R D; Bard, R L; Rubenfire, M; Ridker, P M; Rajagopalan, S

    2001-12-01

    Vascular endothelial dysfunction (VED) is associated with obesity; however, its etiology remains controversial. By determining the predictors of fasting and postprandial endothelial function in overweight adults without other cardiovascular risk factors, we were able to investigate novel mechanisms directly linking obesity to VED. Thirty-two healthy adults (body mass index [BMI] > or =27 kg/m(2)) underwent determination of fasting low-density lipoprotein (LDL) particle size, high sensitivity C-reactive protein levels, anthropometric measurements, and endothelial function by flow-mediated dilation (FMD) of the brachial artery. Postprandial lipemia and FMD were measured 4 hours after ingestion of a high-fat meal. Blood pressures and fasting levels of lipoproteins, glucose, insulin, and fatty acids were within normal limits in all subjects. An abdominal fat pattern, as determined by an increased waist/hip ratio (WHR), was the sole significant predictor of FMD (r = -0.58, p = 0.001), despite no significant correlation between whole body obesity (BMI) and FMD. At comparable levels of BMI, obese subjects with a WHR > or =0.85 had a significantly blunted FMD compared with those with a WHR <0.85 (3.93 +/- 2.85% vs 8.34 +/- 5.47%, p = 0.016). Traditional coronary risk factors, C-reactive protein, postprandial lipemia, and LDL particle size did not predict FMD. We found no appreciable alteration in the postprandial state from fasting FMD (6.31 +/- 4.62% vs 6.25 +/- 5.47%, p = 0.95). The same results were found when women were analyzed alone. Increased abdominal adiposity determined by a simple WHR is a strong independent predictor of VED even in healthy overweight adults; this is a finding unexplained by alterations in conventional risk factors, systemic inflammation, or the atherogenic lipoprotein pattern. PMID:11728354

  8. On the electromagnetic fields produced by marine frequency domain controlled sources

    NASA Astrophysics Data System (ADS)

    Chave, Alan D.

    2009-12-01

    In recent years, marine controlled source electromagnetics (CSEM) has found increasing use in hydrocarbon exploration due to its ability to detect thin resistive zones beneath the seafloor. Although it must be recognized that the quantitative interpretation of marine CSEM data over petroleum-bearing formations will typically require 2-D surveys and 2-D or 3-D modelling, the use of the 1-D approximation is useful under some circumstances and provides considerable insight into the physics of marine CSEM. It is the purpose of this paper to thoroughly explore the 1-D solutions for all four fundamental source types-vertical and horizontal, electric and magnetic dipole (VED, HED, VMD and HMD)-using a set of canonical reservoir models that encompass brine to weak to strong hydrocarbon types. The paper introduces the formalism to solve the Maxwell equations for a 1-D structure in terms of independent and unique toroidal and poloidal magnetic modes that circumscribe the salient diffusion physics. Green's functions for the two modes from which solutions for arbitrary source current distributions can be constructed are derived and used to obtain the electromagnetic (EM) fields produced by finite VED, HED, VMD and HMD sources overlying an arbitrary 1-D electrical structure. Field behaviour is analysed using the Poynting vector that represents the time-averaged flow of energy through the structure and a polarization ellipse decomposition of the triaxial seafloor EM field that is a complete field description. The behaviour of the two EM modes using unimodal VED and VMD sources is presented. The paper closes by extending these results to the bimodal HED and HMD sources.

  9. Computational simulations of vorticity enhanced diffusion

    NASA Astrophysics Data System (ADS)

    Vold, Erik L.

    1999-11-01

    Computer simulations are used to investigate a phenomenon of vorticity enhanced diffusion (VED), a net transport and mixing of a passive scalar across a prescribed vortex flow field driven by a background gradient in the scalar quantity. The central issue under study here is the increase in scalar flux down the gradient and across the vortex field. The numerical scheme uses cylindrical coordinates centered with the vortex flow which allows an exact advective solution and 1D or 2D diffusion using simple numerical methods. In the results, the ratio of transport across a localized vortex region in the presence of the vortex flow over that expected for diffusion alone is evaluated as a measure of VED. This ratio is seen to increase dramatically while the absolute flux across the vortex decreases slowly as the diffusion coefficient is decreased. Similar results are found and compared for varying diffusion coefficient, D, or vortex rotation time, τv, for a constant background gradient in the transported scalar vs an interface in the transported quantity, and for vortex flow fields constant in time vs flow which evolves in time from an initial state and with a Schmidt number of order unity. A simple analysis shows that for a small diffusion coefficient, the flux ratio measure of VED scales as the vortex radius over the thickness for mass diffusion in a viscous shear layer within the vortex characterized by (Dτv)1/2. The phenomenon is linear as investigated here and suggests that a significant enhancement of mixing in fluids may be a relatively simple linear process. Discussion touches on how this vorticity enhanced diffusion may be related to mixing in nonlinear turbulent flows.

  10. Initial validation of a novel rat model of vasculogenic erectile dysfunction with generalized atherosclerosis.

    PubMed

    Park, K; Son, H; Kim, S W; Paick, J-S

    2005-01-01

    Although rats have been widely used in evaluating various causes of vasculogenic erectile dysfunction (VED), the atherosclerotic rat model has seldom been tried probably due to its inherent tolerance to a cholesterol diet. To enhance endothelial sensitivity to cholesterol diet, we tested the effects of transient interruption of nitric oxide synthase on atherogenesis induced by cholesterol diet in a rat model. Rats with atherosclerosis (AS group) received 1% cholesterol diet for 6 weeks. During the initial 2 weeks, they drank water that contained N(G)-nitro-L-arginine methyl ester (L-NAME) (3 mg/ml). After 6 weeks, we carried out histologic and hemodynamic evaluation to confirm pelvic atherosclerosis and erectile dysfunction, respectively, and the results were compared with those of cholesterol only (Chol) group and normal control (C) group. Compared to the C or Chol group, the mean intima/media (I/M) of the internal pudendal artery, which contributes approximately 70% of the total resistance of the penile vasculature, was markedly increased by the treatment (1.82+/-0.25 vs 0.77+/-0.13, P<0.05). Correspondingly, significantly diminished erectile function was observed. Combined treatment for 2 weeks elicited early atherosclerotic changes in proximal arteries and erectile impairment and further 4 weeks of cholesterol diet spread overt atherosclerosis to the periphery. The Chol group showed no arterial pathology, although they showed mild VED. A correlation study showed that atherosclerosis of the distal artery was better correlated with erectile dysfunction than the proximal artery. Based on these results, our study demonstrates that combination treatment of cholesterol diet with L-NAME would be used as a rapid, effective protocol of developing atherosclerotic rat model of VED. PMID:15889122

  11. Effects of chronic methamphetamine exposure on heart function in uninfected and retrovirus-infected mice.

    PubMed

    Yu, Qianli; Montes, Sergio; Larson, Douglas F; Watson, Ronald R

    2002-07-12

    Methamphetamine (MA) increases catecholamine levels, which have detrimental effects on heart function through vasoconstriction, myocardial hypertrophy, and fibrosis. Murine retrovirus infection induces dilated cardiomyopathy (DCM). The present study investigated the cardiovascular effects of chronic MA treatment on uninfected and retrovirus-infected mice. C57BL/6 mice were studied after 12 weeks treatment. The four study groups were (group I) uninfected, MA placebo; (group II) infected, MA placebo; (group III) uninfected, MA treatment; and (group IV) infected and MA treatment. MA injections were given i.p. once a day for 5 days/week with a increasing dose from 15 mg/kg to 40 mg/kg. Left ventricular mechanics were measured in situ a using Millar conductance catheter system for pressure-volume loop analysis. Cardiac pathology was determined with histological analysis. In the uninfected mice, the load independent contractile parameters, pre-load recruitable stroke work (PRSW) and dP/dt(max) vs. Ved, significantly decreased by 32% and 35% in MA treated mice when compared to the saline injected mice. In retrovirus-infected mice, although there were no significant difference in Ees, PRSW, and dP/dt(max) vs. Ved due to MA treatment, they were increased 45%, 15% and 42% respectively when compared to saline treated mice. No further lowered heart function during murine AIDS may be due to the counteraction of the retroviral DCM and the MA induced myocardial fibrosis and hypertrophy (thickening of the ventricular walls). This is supported by increases in the End-diastolic volume (Ved, 38%) and End-systolic volume (Ves, 84%) in the retrovirus-infected saline injected mice, the decreases of 33% and 17% in the uninfected MA-treated mice, but no significant changes in the retrovirus-infected MA treated mice when compared to uninfected saline injected mice. These data suggest that MA induced myocardial cellular changes compensate for retrovirus induced DCM. PMID:12084392

  12. Autoimmune-Like Hepatitis: A "Hepatitic" Manifestation of Chronic Graft Versus Host Disease in Post-Stem Cell Transplant.

    PubMed

    Baniak, Nick M; Kanthan, Rani

    2016-04-01

    A 59-year-old female received a matched related donor stem cell transplant for chronic myelogenous leukemia. After being successfully treated with prednisone for chronic graft versus host disease that initially started 50 days posttransplant, she developed hepatic dysfunction during the steroid taper on day 531, as evidenced by jaundice, elevated liver enzymes, and increased bilirubin. Liver biopsy showed histology suggestive of autoimmune-like hepatitis, which is a rare manifestation of chronic "hepatitic" graft versus host disease. PMID:26464160

  13. ESPGHAN Committee on Nutrition Position Paper. Intravenous Lipid Emulsions and Risk of Hepatotoxicity in Infants and Children: a Systematic Review and Meta-analysis.

    PubMed

    Hojsak, Iva; Colomb, Virginie; Braegger, Christian; Bronsky, Jiri; Campoy, Cristina; Domellöf, Magnus; Embleton, Nicholas; Fidler Mis, Nataša; Hulst, Jessie M; Indrio, Flavia; Lapillonne, Alexandre; Mihatsch, Walter; Molgaard, Christian; van Goudoever, Johannes; Fewtrell, Mary

    2016-05-01

    The aim of the present article was to perform a systematic review with meta-analysis of available scientific evidence regarding the role of different intravenous lipid emulsions (ILE) in the pathogenesis of cholestasis and parenteral nutrition-associated liver disease. A systematic review of the literature (up to March 2015) identified 23 randomized controlled trials (RCTs). Of these, 17 were performed in preterm infants or critically ill neonates with a short duration of intervention, 2 in older children with short-term use (following surgery or bone marrow transplantation), 1 in neonates with long-term use, and 3 in infants and children receiving long-term parenteral nutrition (PN). Meta-analysis showed no differences in the rate of cholestasis or bilirubin levels associated with short-term use of different ILEs. Because of high heterogeneity of the long-term studies no meta-analysis could be performed. Available studies found that the use of multicomponent fish oil (FO)-containing ILE compared with pure soya bean oil (SO), ILE-reduced liver enzymes, and bilirubin levels in noncholestatic children on long-term PN and one other RCT found that FO-based ILE-reversed cholestasis in a proportion of patients. The ESPGHAN Committee on Nutrition concludes that there is no evidence of a difference in rates of cholestasis or bilirubin levels between different ILE for short-term use in neonates. The use of multicomponent FO-containing ILE may contribute to a decrease in total bilirubin levels in children with IF on prolonged PN. Well-designed RCTs are, however, lacking and long-term effects have not been determined. PMID:26825766

  14. A membraneless air-breathing hydrogen biofuel cell based on direct wiring of thermostable enzymes on carbon nanotube electrodes.

    PubMed

    Lalaoui, Noémie; de Poulpiquet, Anne; Haddad, Raoudha; Le Goff, Alan; Holzinger, Michael; Gounel, Sébastien; Mermoux, Michel; Infossi, Pascale; Mano, Nicolas; Lojou, Elisabeth; Cosnier, Serge

    2015-05-01

    A biocathode was designed by the modification of a carbon nanotube (CNT) gas-diffusion electrode with bilirubin oxidase from Bacillus pumilus, achieving high current densities up to 3 mA cm(-2) for the reduction of O2 from air. A membraneless air-breathing hydrogen biofuel cell was designed by combination of this cathode with a functionalized CNT-based hydrogenase anode. PMID:25845356

  15. A Pharmacologic View of Phototherapy.

    PubMed

    Lamola, Angelo A

    2016-06-01

    A pharmacologic view of phototherapy for neonatal jaundice is presented. By considering the photons of therapy light as molecules of a drug, this view connects therapeutic efficacy with photon wavelength, photon dose, dose rate and regimen, efficiency of photon absorption by bilirubin, quantum yields of photoproducts, and their metabolic courses. Based on this view, recommendations to ultimately improve efficacy and safety are presented. Special attention is given to phototherapy regimens for low gestational age, low birthweight infants. PMID:27235206

  16. Eel green fluorescent protein is associated with resistance to oxidative stress.

    PubMed

    Funahashi, Aki; Komatsu, Masaharu; Furukawa, Tatsuhiko; Yoshizono, Yuki; Yoshizono, Hikari; Orikawa, Yasuhiro; Takumi, Shota; Shiozaki, Kazuhiro; Hayashi, Seiichi; Kaminishi, Yoshio; Itakura, Takao

    2016-01-01

    Green fluorescent protein (GFP) from eel (Anguilla japonica) muscle (eelGFP) is unique in the vertebrates and requires bilirubin as a ligand to emit fluorescence. This study was performed to clarify the physiological function of the unique GFP. Investigation of susceptibility to oxidative stress was carried out using three types of cell lines including jellyfish (Aequorea coerulescens) GFP (jfGFP)-, or eel GFP (eelGFP)-expressing HEK293 cells, and control vector-transfected HEK293 cells. Binding of eelGFP to bilirubin was confirmed by the observation of green fluorescence in HEK293-eelGFP cells. The growth rate was compared with the three types of cells in the presence or absence of phenol red which possessed antioxidant activity. The growth rates of HEK293-CV and HEK293-jfGFP under phenol red-free conditions were reduced to 52 and 31% of those under phenol red. Under the phenol red-free condition, HEK293-eelGFP had a growth rate of approximately 70% of the phenol red-containing condition. The eelGFP-expressing cells were approximately 2-fold resistant to oxidative stress such as H2O2 exposure. The fluorescence intensity partially decreased or disappeared after exposure to H2O2, and heterogeneous intensity of fluorescence was also observed in isolated eel skeletal muscle cells. These results suggested eelGFP, but not jfGFP, coupled with bilirubin provided the antioxidant activity to the cells as compared to non-bound free bilirubin. PMID:26746389

  17. Impaired cholecystokinin-induced gallbladder emptying incriminated in spontaneous “black” pigment gallstone formation in germfree Swiss Webster mice

    PubMed Central

    Woods, Stephanie E.; Leonard, Monika R.; Hayden, Joshua A.; Brophy, Megan Brunjes; Bernert, Kara R.; Lavoie, Brigitte; Muthupalani, Sureshkumar; Mawe, Gary M.; Nolan, Elizabeth M.; Carey, Martin C.; Fox, James G.

    2014-01-01

    “Black” pigment gallstones form in sterile gallbladder bile in the presence of excess bilirubin conjugates (“hyperbilirubinbilia”) from ineffective erythropoiesis, hemolysis, or induced enterohepatic cycling (EHC) of unconjugated bilirubin. Impaired gallbladder motility is a less well-studied risk factor. We evaluated the spontaneous occurrence of gallstones in adult germfree (GF) and conventionally housed specific pathogen-free (SPF) Swiss Webster (SW) mice. GF SW mice were more likely to have gallstones than SPF SW mice, with 75% and 23% prevalence, respectively. In GF SW mice, gallstones were observed predominately in heavier, older females. Gallbladders of GF SW mice were markedly enlarged, contained sterile black gallstones composed of calcium bilirubinate and <1% cholesterol, and had low-grade inflammation, edema, and epithelial hyperplasia. Hemograms were normal, but serum cholesterol was elevated in GF compared with SPF SW mice, and serum glucose levels were positively related to increasing age. Aged GF and SPF SW mice had deficits in gallbladder smooth muscle activity. In response to cholecystokinin (CCK), gallbladders of fasted GF SW mice showed impaired emptying (females: 29%; males: 1% emptying), whereas SPF SW females and males emptied 89% and 53% of volume, respectively. Bilirubin secretion rates of GF SW mice were not greater than SPF SW mice, repudiating an induced EHC. Gallstones likely developed in GF SW mice because of gallbladder hypomotility, enabled by features of GF physiology, including decreased intestinal CCK concentration and delayed intestinal transit, as well as an apparent genetic predisposition of the SW stock. GF SW mice may provide a valuable model to study gallbladder stasis as a cause of black pigment gallstones. PMID:25477375

  18. Human neonatal hepatocyte transplantation induces long-term rescue of unconjugated hyperbilirubinemia in the Gunn rat.

    PubMed

    Tolosa, Laia; López, Silvia; Pareja, Eugenia; Donato, María Teresa; Myara, Anne; Nguyen, Tuan Huy; Castell, José Vicente; Gómez-Lechón, María José

    2015-06-01

    Crigler-Najjar type 1 disease is a rare inherited metabolic disease characterized by high levels of unconjugated bilirubin due to the complete absence of hepatic uridine diphosphoglucuronate-glucuronosyltransferase activity. Hepatocyte transplantation (HT) has been proposed as an alternative treatment for Crigler-Najjar syndrome, but it is still limited by the quality and the low engraftment and repopulation ability of the cells used. Because of their attachment capability and expression of adhesion molecules as well as the higher proportion of hepatic progenitor cells, neonatal hepatocytes may have an advantage over adult cells. Adult or neonatal hepatocytes were transplanted into Gunn rats, a model for Crigler-Najjar disease. Engraftment and repopulation were studied and compared by immunofluorescence (IF). Additionally, the serum bilirubin levels, the presence of bilirubin conjugates in rat serum, and the expression of uridine diphosphate glucuronosyltransferase 1 family polypeptide A1 (UGT1A1) in rat liver samples were also analyzed. Here we show that neonatal HT results in long-term correction in Gunn rats. In comparison with adult cells, neonatal cells showed better engraftment and repopulation capability 3 days and 6 months after transplantation, respectively. Bilirubinemia decreased in the transplanted animals during the whole experimental follow-up (6 months). Bilirubin conjugates were also present in the serum of the transplanted animals. Western blots and IF confirmed the presence and expression of UGT1A1 in the liver. This work is the first to demonstrate the advantage of using neonatal hepatocytes for the treatment of Crigler-Najjar in vivo. PMID:25821167

  19. The Effect of UGT1A1 Promoter Polymorphism in the Development of Hyperbilirubinemia and Cholelithiasis in Hemoglobinopathy Patients

    PubMed Central

    AlFadhli, Suad; Al-Jafer, Hassan; Hadi, Mays; Al-Mutairi, Mashael; Nizam, Rasheeba

    2013-01-01

    Present study was aimed to explore the effect of (TA)n UGT1A1 gene promoter polymorphism on bilirubin metabolism, bilirubinaemia, predisposition to cholelithiasis and subsequent cholecystectomy, in Sickle-Cell Anemia (SCA) and beta-Thalasemia major (bTH) in Kuwaiti subjects compared to other population. This polymorphism was analyzed and correlated to total bilirubin and cholelithiasis in 270 age, gender, ethnically matched subjects (92 bTH, 116 SCA and 62 Controls) using PCR, dHPLC, fragment analysis and direct sequencing. Four genotypes of UGT1A1 were detected in this study (TA6/6, TA6/7, TA6/8 and TA7/7). (TA)6/8 was found only in four individuals; hence it was not included in the analysis. There was a statistically significant association of genotypes with serum total bilirubin levels in both bTH and SCA groups (p<0.001). Subjects with (TA)7/7 had the highest total serum bilirubin level (178.7±3.5 µmole/l). A significant association was observed between allele (TA)7 and cholelithiasis development (p = 0.0001). The 40%, 67.5% and 100% of SCA with (TA)6/6, (TA)6/7 and (TA)7/7 respectively developed cholelithiasis and were subsequently cholecystectomized. Our results confirm UGT1A1 (TA)7 allele as one of the factors accounting for the hyperbilirubinemia and cholelithiasis observed in SCA and bTH. PMID:24204915

  20. New pathophysiological concepts underlying pathogenesis of pigment gallstones

    PubMed Central

    Vítek, Libor; Carey, Martin C.

    2011-01-01

    SUMMARY Pigment gallstones, which are much less frequent than cholesterol stones, are classified descriptively as ‘black’ or ‘brown’. They are composed mostly of calcium hydrogen bilirubinate, Ca(HUCB)2, which is polymerized and oxidized in ‘black‘ stones but remains unpolymerized in ‘brown’ stones. Black stones form in sterile gallbladder bile but brown stones form secondary to stasis and anaerobic bacterial infection in any part of the biliary tree, including the gallbladder. Other calcium salts coprecipitate in both stone types; crystalline calcium phosphate and/or carbonate in the case of ‘black’ stones and amorphous calcium salts of long chain saturated fatty acids (‘soaps’) in the case of ‘brown’ stones. Cholesterol is present in variable proportions in ‘brown’ more than ‘black’ stones and, in the latter, the bile sterol may be totally absent. The ‘scaffolding’ of both stone types is a mixed mucin glycoprotein matrix secreted by epithelial cells lining the biliary tree. The critical pathophysiological prerequisite for ‘black’ stone formation is ‘hyperbilirubinbilia’ (biliary hypersecretion of bilirubin conjugates). It is due principally to hemolysis, ineffective erythropoiesis, or pathologic enterohepatic cycling of unconjugated bilirubin. Endogenous biliary β-glucuronidase hydrolysis of bilirubin conjugates in gallbladder bile provides HUCB− molecules that precipitate as insoluble salts with ionized Ca. Putatively, reactive oxygen species secreted by an inflamed gallbladder mucosa are responsible for transforming the initial soft yellow precipitates into hard black [Ca(HUCB)2]n polymers. Despite ‘brown’ gallstones being soft and amenable to mechanical removal, chronic anaerobic infection of the biliary tree is often markedly resistant to eradication. PMID:21978438