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

NARCIS (Netherlands)

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

1986-01-01

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

Blood Test: Bilirubin

Science.gov (United States)

... Videos for Educators Search English Español Blood Test: Bilirubin KidsHealth / For Parents / Blood Test: Bilirubin What's in ... liver or kidneys) is working. What Is a Bilirubin Test? A bilirubin test measures how much bilirubin ...

Serum Bilirubin Concentrations in Patients With Takayasu Arteritis.

Science.gov (United States)

Peng, You-Fan; Deng, Yi-Bin

2017-06-01

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

Newborn Jaundice Technologies: Unbound Bilirubin and Bilirubin Binding Capacity In Neonates

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Amin, Sanjiv B.; Lamola, Angelo A.

2011-01-01

Neonatal jaundice (hyperbilirubinemia), extremely common in neonates, can be associated with neurotoxicity. A safe level of bilirubin has not been defined in either premature or term infants. Emerging evidence suggest that the level of unbound (or “free”) bilirubin has a better sensitivity and specificity than total serum bilirubin for bilirubin-induced neurotoxicity. Although recent studies suggest the usefulness of free bilirubin measurements in managing high-risk neonates including premature infants, there currently exists no widely available method to assay the serum free bilirubin concentration. To keep pace with the growing demand, in addition to reevaluation of old methods, several promising new methods are being developed for sensitive, accurate, and rapid measurement of free bilirubin and bilirubin binding capacity. These innovative methods need to be validated before adopting for clinical use. We provide an overview of some promising methods for free bilirubin and binding capacity measurements with the goal to enhance research in this area of active interest and apparent need. PMID:21641486

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

Science.gov (United States)

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

2016-01-05

Hyperbilirubinemia is a common clinical phenomenon observed in human newborns. A high level of bilirubin can result in severe jaundice and bilirubin encephalopathy. However, the cellular mechanisms underlying bilirubin excitotoxicity are unclear. Our previous studies showed the action of gamma-aminobutyric acid (GABA)/glycine switches from excitatory to inhibitory during development in the ventral cochlear nucleus (VCN), one of the most sensitive auditory nuclei to bilirubin toxicity. In the present study, we investigated the roles of GABAA/glycine receptors in the induction of bilirubin hyperexcitation in early developing neurons. Using the patch clamp technique, GABAA/glycine receptor-mediated spontaneous inhibitory synaptic currents (sIPSCs) were recorded from bushy and stellate cells in acute brainstem slices from young mice (postnatal day 2-6). Bilirubin significantly increased the frequency of sIPSCs, and this effect was prevented by pretreatments of slices with either fast or slow Ca(2+) chelators BAPTA-AM and EGTA-AM suggesting that bilirubin can increase the release of GABA/glycine via Ca(2+)-dependent mechanisms. Using cell-attached recording configuration, we found that antagonists of GABAA and glycine receptors strongly attenuated spontaneous spiking firings in P2-6 neurons but produced opposite effect in P15-19 neurons. Furthermore, these antagonists reversed bilirubin-evoked hyperexcitability in P2-6 neurons, indicating that excitatory action of GABA/glycinergic transmission specifically contribute to bilirubin-induced hyperexcitability in the early stage of development. Our results suggest that bilirubin-induced enhancement of presynaptic release GABA/Glycine via Ca(2+)-dependent mechanisms may play a critical role in mediating neuronal hyperexcitation associated with jaundice, implicating potential new strategies for predicting, preventing, and treating bilirubin neurotoxicity. Copyright © 2015. Published by Elsevier Ireland Ltd.

Cerebral blood flow and liver function in patients with encephalopathy due to acute and chronic liver diseases

DEFF Research Database (Denmark)

Almdal, T; Schroeder, T; Ranek, L

1989-01-01

The purpose of the present investigation was to study changes in cerebral blood flow (CBF) in hepatic encephalopathy, to ascertain whether this was related to the changes in liver function and whether these changes gave any prognostic information. CBF, determined by the intravenous xenon-133 method......, and liver functions, assessed by the prothrombin index, bilirubin concentration, and the galactose elimination capacity, were studied in patients with acute fulminant liver failure and in patients with encephalopathy due to chronic liver diseases--that is, cirrhosis of various etiologies. The CBF range...

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

International Nuclear Information System (INIS)

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

2005-01-01

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

Bilirubin-albumin binding, bilirubin/albumin ratios, and free bilirubin levels : Where do we stand?

NARCIS (Netherlands)

Hulzebos, Christian V.; Dijk, Peter H.

2014-01-01

Treatment for unconjugated hyperbilirubinemia is predominantly based on one parameter, i.e., total serum bilirubin (TSB) levels. Yet, overt kernicterus has been reported in preterm infants at relatively low TSB levels, and it has been repeatedly shown that free unconjugated bilirubin (freeUCB)

Cerebral CT appearances of toxic encephalopathy of tetramine

International Nuclear Information System (INIS)

Zheng Wenlong; Wu Aiqin; Xu Chongyong; Ying Binyu; Hong Ruizhen

2003-01-01

Objective: To investigate the cerebral CT appearances of toxic encephalopathy of tetramine and improve the recognition on this disease. Methods: Four cases of toxic encephalopathy of tetramine were collected and their cerebral CT appearances were retrospectively analyzed. Results: Cerebral CT appearances in acute phase (within 8 days): (1) cerebral edema in different degree. CT abnormalities consisted of cortical hypodensities and complete loss of gray-white matter differentiation. The CT value were in 11-13 HU, and to be watery density in serious case, (2) subarachnoid hemorrhage. It demonstrated the signs of poisoning hypoxic ischemic encephalopathy in chronic phase. Conclusion: The cerebral CT appearances of toxic encephalopathy of tetramine had some character in acute phase and it can predict the serious degree of intoxication, but there was no characteristic findings in chronic phase

Bilirubin glucuronidation by intact Gunn rat fibroblasts expressing bilirubin UDP-glucuronosyltransferase

NARCIS (Netherlands)

Seppen, J.; Tada, K.; Hellwig, S.; Bakker, C. T.; Prasad, V. R.; Roy Chowdhury, N.; Roy Chowdhury, J.; Bosma, P. J.; Oude Elferink, R. P.

1996-01-01

Crigler-Najjar (CN) disease is an inherited disorder of bilirubin metabolism. The disease is caused by a deficiency of the hepatic enzyme bilirubin UDP-glucuronosyltransferase (B-UGT). Patients with CN disease have high serum levels of the toxic compound, unconjugated bilirubin. The only defect in

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

Science.gov (United States)

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

[Expression of aquaporin-4 during brain edema in rats with thioacetamide-induced acute encephalopathy].

Science.gov (United States)

Wang, Li-Qing; Zhu, Sheng-Mei; Zhou, Heng-Jun; Pan, Cai-Fei

2011-09-27

To investigate the expression of aquaporin-4 (AQP4) during brain edema in rats with thioacetamide-induced acute liver failure and encephalopathy. The rat model of acute hepatic failure and encephalopathy was induced by intraperitoneal injection of thioacetamide (TAA) at a 24-hour interval for 2 consecutive days. Thirty-two SD rats were randomly divided into the model group (n = 24) and the control group (normal saline, n = 8). And then the model group was further divided into 3 subgroups by the timepoint of decapitation: 24 h (n = 8), 48 h (n = 8) and 60 h (n = 8). Then we observed their clinical symptoms and stages of HE, indices of liver function and ammonia, liver histology and brain water content. The expression of AQP4 protein in brain tissues was measured with Western blot and the expression of AQP4mRNA with RT-PCR (reverse transcription-polymerase chain reaction). Typical clinical manifestations of hepatic encephalopathy occurred in all TAA-administrated rats. The model rats showed the higher indices of ALT (alanine aminotransferase), AST (aspartate aminotransferase), TBIL (total bilirubin) and ammonia than the control rats (P liver failure and encephalopathy plays a significant role during brain edema. AQP4 is one of the molecular mechanisms for the occurrence of brain edema in hepatic encephalopathy.

Comparison of Transcutaneous Bilirubin Measurement With Total Serum Bilirubin Levels in Preterm Neonates Receiving Phototherapy.

Science.gov (United States)

Pendse, Amruta; Jasani, Bonny; Nanavati, Ruchi; Kabra, Nandkishor

2017-08-15

To compare transcutaneous bilirubin with total serum bilirubin in preterm neonates after initiation of phototherapy. Jaundice was assessed in 30 preterm neonates with transcutaneous bilirubin and total serum bilirubin before initiation of phototherapy and at 12 hr after initiation of phototherapy. A photo-occlusive patch was applied over the sternum. Transcutaneous bilirubin has a good correlation with total serum bilirubin after initiation of phototherapy. (r=0.918, Pbilirubin at 28-32 weeks of gestation (r = 0.97) was better correlated with total serum bilirubin than those at 32-37 weeks (r =0.88). The correlation was better for neonates 72 hours of age (r = 0.82). Transcutaneous bilirubin correlates significantly with total serum bilirubin at the patched sternal site after initiation of phototherapy in preterm neonates.

Bilirubin and atherosclerotic diseases.

Science.gov (United States)

Vítek, L

2017-04-05

Bilirubin is the final product of heme catabolism in the systemic circulation. For decades, increased serum/plasma bilirubin levels were considered an ominous sign of an underlying liver disease. However, data from recent years convincingly suggest that mildly elevated bilirubin concentrations are associated with protection against various oxidative stress-mediated diseases, atherosclerotic conditions being the most clinically relevant. Although scarce data on beneficial effects of bilirubin had been published also in the past, it took until 1994 when the first clinical study demonstrated an increased risk of coronary heart disease in subjects with low serum bilirubin levels, and bilirubin was found to be a risk factor for atherosclerotic diseases independent of standard risk factors. Consistent with these results, we proved in our own studies, that subjects with mild elevation of serum levels of unconjugated bilirubin (benign hyperbilirubinemia, Gilbert syndrome) have much lower prevalence/incidence of coronary heart as well as peripheral vascular disease. We have also demonstrated that this association is even more general, with serum bilirubin being a biomarker of numerous other diseases, often associated with increased risk of atherosclerosis. In addition, very recent data have demonstrated biological pathways modulated by bilirubin, which are responsible for observed strong clinical associations.

Inherited Disorders of Bilirubin Clearance

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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

Liver function test with 99mTc-labelled bilirubin in children

International Nuclear Information System (INIS)

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

1989-01-01

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

Risk factors of kernicterus; a study in 312 icteric neonates

Directory of Open Access Journals (Sweden)

Behjati Ardakani S

2007-07-01

Full Text Available Background: Kernicterus, also known as bilirubin encephalopathy, is a neurologic syndrome resulting from the deposition of unconjugated bilirubin in the basal ganglia and brainstem nuclei. Indirect bilirubin is toxic for brain. Neurologic dysfunction (BIND that include acute phase (hyperbilirubin encephalopathy and chronic phase (Kernicterus resulting from hyperbilirubinemia and disruption of blood brain barrier. In this study, the association between bilirubin encephalopathy and risk factors was evaluated. Methods: In this retrospective study, 312 icteric neonates were admitted in the neonatal ward of Children's Hospital, Medical Center, Tehran, and 305 of these cases were evaluated. Patient histories were taken and physical examinations were performed. For each patient, the age, sex, birth weight, time of discharge from the hospital and risk factors were recorded, and a questionnaire was completed. Results: In this study, of the 305 icteric neonates evaluated, 25 cases had kernicterus. Risk factors included acidosis, prematurity, hemolysis, hypoglycemia, sepsis, respiratory distress, low birth weight, ABO incompatibility and G6PD deficiency. The mean level of bilirubin in cases of kernicterus was 32 mg/dl and in the others was 20 mg/dl (p=0.001. Kernicterus was most common among high risk neonates (p<0.001. Birth weight less than 2,500 gm was also an important factor (p=0.04. Conclusion: High-risk neonates need prompt treatment for hyperbilirubinemia compared to low risk neonates.

[Changes in serotonin and noradrenaline in hepatic encephalopathy as a result of liver failure in rat].

Science.gov (United States)

Song, Min-ning; Song, Yu-na; Chen, Fu; Luo, Mei-lan

2007-01-01

To investigate the changes in serotonin (5-HT) and noradrenaline (NA) in hepatic encephalopathy as a result of acute and chronic liver failure in rat. One hundred and ten Sprague-Dawley (SD) rats were randomly divided into groups of normal control (n=20), experimental group of acute liver failure (ALF) encephalopathy (n=45), and experimental group of chronic liver failure (CLF) encephalopathy (n=45). Two dosages of thioacetamide (TAA) of 500 mg/kg were gavaged with an interval of 24 hours to reproduce ALF model. To reproduce CLF model rats were fed with 0.03% TAA in drinking water for 10 weeks, and 50% of TAA dosage was added or withheld according to the change in weekly body weight measurement. Animals were sacrificed and venous blood specimens were obtained after successful replication of model, and 5-HT, NA, ammonia, parameters of liver function were determined, and liver and brain were studied pathologically. The experiment showed that the liver functions of rats in groups ALF encephalopathy and CLF encephalopathy deteriorated seriously, changes in alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), albumen (ALB), ALB/globulin (A/G), and blood ammonia were observed(Pliver and brain pathologies were identical to those of ALF and CLF encephalopathy. The values of 5-HT were increased in groups ALF encephalopathy and CLF encephalopathy [(16.06+/-1.08) micromol/L and (15.32+/-1.48) micromol/L] compared with the normal group [(2.75+/-0.26) micromol/L, both Pencephalopathy [(94.0+/-2.13) pmol/L vs.(121.2+/-14.8) pmol/L,Pencephalopathy and CLF encephalopathy. The content of NA decreases remarkably in CLF encephalopathy.

Early predictive value of cord blood bilirubin and dynamic monitoring of transcutaneous bilirubin for hyperbilirubinemia of newborns

Directory of Open Access Journals (Sweden)

Haishan Guan

2017-12-01

Conclusions: The increase of cord blood bilirubin effectively predict the occurrence of neonatal hyperbilirubinemia. There is a good correlation between levels of transcutaneous bilirubin and serum bilirubin. Moreover, combined detection of transcutaneous bilirubin and cord blood bilirubin can significantly improve the prediction accuracy of hyperbilirubinemia.

Brain magnetic resonance imaging in acute phase of pandemic influenza A (H1N1) 2009--associated encephalopathy in children.

Science.gov (United States)

Ishida, Yu; Kawashima, Hisashi; Morichi, Shinichiro; Yamanaka, Gaku; Okumura, Akihisa; Nakagawa, Satoshi; Morishima, Tsuneo

2015-02-01

Pandemic influenza A (H1N1) 2009 has been shown to be associated more with neurological complications than the seasonal influenza virus. In this study, we focused on the clinical usefulness of magnetic resonance imaging (MRI) in the acute phase of influenza A (H1N1) 2009-associated encephalopathy. A questionnaire was distributed to pediatric and general hospitals in Japan that treat children with encephalopathy. We conducted a questionnaire-based study involving the collection of information regarding 207 patients with encephalopathy. Brain MRI was performed in 97 of these 207 patients in the age group of 9 months to 15 years (mean, 7.5 years) within 48 hours after the development of encephalopathy symptoms. Sixty-six patients (68%) showed normal imaging. Diffuse brain edema was visible in five patients and an abnormal signal in the deep gray matter in two patients which is consistent with acute necrotizing encephalopathy. Abnormal signals of the splenial lesion, subcortical white matter (bright tree appearance), and cortical area were observed in 15, 1, and 8 patients, respectively. From our findings based on the questionnaire results, we suggest that MRI is useful for determining fatal cases of pandemic influenza A (H1N1) 2009 infection when performed in the acute phase. However, MRI is not useful in predicting the development of sequelae. Georg Thieme Verlag KG Stuttgart · New York.

Usefulness of the bilirubin/albumin ratio for predicting bilirubin-induced neurotoxicity in premature infants

NARCIS (Netherlands)

Hulzebos, C. V.; van Imhoff, D. E.; Bos, A. F.; Ahlfors, C. E.; Verkade, H. J.; Dijk, P. H.

Unconjugated hyperbilirubinaemia occurs in almost all premature infants and is potentially neurotoxic. Treatment is based on total serum bilirubin (TSB), but treatment thresholds are not evidence based. Free bilirubin (Bf) - that is, not bound to albumin, seems a better parameter for bilirubin

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

International Nuclear Information System (INIS)

Vanstapel, F.; Blanckaert, N.

1987-01-01

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

Biology of Bilirubin Photoisomers.

Science.gov (United States)

Hansen, Thor Willy Ruud

2016-06-01

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

Bilirubin present in diverse angiosperms.

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

2010-01-01

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

Photoacoustic microscopy of bilirubin in tissue phantoms

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

2012-12-01

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

Bilirubin Binding Capacity in the Preterm Neonate.

Science.gov (United States)

Amin, Sanjiv B

2016-06-01

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

Quantitative imaging of bilirubin by photoacoustic microscopy

Science.gov (United States)

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

2013-03-01

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

Bilirubin Binding to PPARα Inhibits Lipid Accumulation

Science.gov (United States)

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

Hepatic Encephalopathy

Science.gov (United States)

... Caregiver Support Caregiver Stories Home › What is Hepatic Encephalopathy? Why Your Liver is Important The Connection Between HE and Liver ... Why it’s Important to Treat HE Symptoms of Liver Failure Glossary of terms ... is Hepatic Encephalopathy? Hepatic Encephalopathy, sometimes referred to as portosystemic encephalopathy ...

Hepatic Encephalopathy

Medline Plus

Full Text Available ... Caregiver Support Caregiver Stories Home › What is Hepatic Encephalopathy? Why Your Liver is Important The Connection Between HE and Liver ... Why it’s Important to Treat HE Symptoms of Liver Failure Glossary of terms ... is Hepatic Encephalopathy? Hepatic Encephalopathy, sometimes referred to as portosystemic encephalopathy ...

Current pathogenetic aspects of hepatic encephalopathy and noncirrhotic hyperammonemic encephalopathy.

Science.gov (United States)

Cichoż-Lach, Halina; Michalak, Agata

2013-01-07

Hepatic encephalopathy is a medical phenomenon that is described as a neuropsychiatric manifestation of chronic or acute liver disease that is characterized by psychomotor, intellectual and cognitive abnormalities with emotional/affective and behavioral disturbances. This article focuses on the underlying mechanisms of the condition and the differences between hepatic encephalopathy and noncirrhotic hyperammonemic encephalopathy. Hepatic encephalopathy is a serious condition that can cause neurological death with brain edema and intracranial hypertension. It is assumed that approximately 60%-80% of patients with liver cirrhosis develop hepatic encephalopathy. This review explores the complex mechanisms that lead to hepatic encephalopathy. However, noncirrhotic hyperammonemic encephalopathy is not associated with hepatic diseases and has a completely different etiology. Noncirrhotic hyperammonemic encephalopathy is a severe occurrence that is connected with multiple pathogeneses.

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

International Nuclear Information System (INIS)

Sturrock, E.D.

1994-04-01

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

Hepatic Encephalopathy

Medline Plus

Full Text Available ... Donate Today Enroll in 123 What is Hepatic Encephalopathy? Hepatic Encephalopathy, sometimes referred to as portosystemic encephalopathy or PSE, is a condition that causes temporary ...

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

OpenAIRE

石川, 泰祐

1980-01-01

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

Reversible cortical blindness in a case of hepatic encephalopathy

Directory of Open Access Journals (Sweden)

Amlan Kanti Biswas

2016-01-01

Full Text Available Hepatic encephalopathy is a frequent and often fatal manifestation of chronic liver disease. The pathogenesis of hepatic encephalopathy is believed to be multifactorial including impaired blood-brain barrier function, imbalance between the excitatory and inhibitory neurotransmitters in cortex, accumulation of various toxic and false neurotransmitters, and lack of nutrients like oxygen and glucose. Signs and symptoms of hepatic encephalopathy varies and commonly ranges from personality changes, disturbed consciousness, sleep pattern alternation, intellectual deterioration, speech disturbances, asterixis to frank coma and even death. Reversible or transient cortical blindness is rare manifestation of hepatic encephalopathy. It may even precede the phase of altered consciousness in such patients. Very few similar cases have been reported worldwide. Hence, we would like to report a case of transient cortical blindness in a patient of hepatic encephalopathy.

Photodamage of the cells in culture sensitized with bilirubin

Science.gov (United States)

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

2016-08-01

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

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

Science.gov (United States)

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

2013-01-01

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

Functionalized SBA-15 materials for bilirubin adsorption

Science.gov (United States)

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

2011-05-01

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

CT and MRI findings of cyclosporine-related encephalopathy and hypertensive encephalopathy

International Nuclear Information System (INIS)

Yamamoto, Akira; Hayakawa, Katsumi; Houjyou, Makoto

2002-01-01

We present the MRI and CT findings of one child with cyclosporine-related encephalopathy, and one child with hypertensive encephalopathy following cyclosporine-related encephalopathy. The imaging findings were shown well on T2-weighted and fluid-attenuated inversion recovery (FLAIR) MR images. Cyclosporine-related encephalopathy was distributed predominantly in the posterior white matter. Hypertensive encephalopathy showed similar changes of CT attenuation, but with wider distribution. These two disorders seem to have the same pathogenesis. (orig.)

The effect of gamma-radiation on bilirubin

International Nuclear Information System (INIS)

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

2001-01-01

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

Current pathogenetic aspects of hepatic encephalopathy and noncirrhotic hyperammonemic encephalopathy

OpenAIRE

Cichoż-Lach, Halina; Michalak, Agata

2013-01-01

Hepatic encephalopathy is a medical phenomenon that is described as a neuropsychiatric manifestation of chronic or acute liver disease that is characterized by psychomotor, intellectual and cognitive abnormalities with emotional/affective and behavioral disturbances. This article focuses on the underlying mechanisms of the condition and the differences between hepatic encephalopathy and noncirrhotic hyperammonemic encephalopathy. Hepatic encephalopathy is a serious condition that can cause ne...

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

NARCIS (Netherlands)

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

1978-01-01

The microsomal enzyme uridine diphosphate (UDP) glucuronate glucuronyltransferase (E.C. 2.4.1.17) catalyzes formation of bilirubin mono-glucuronide from bilirubin and UDPglucuronic acid. Bilirubin glucuronoside glucuronosyltransferase (E.C. 2.4.1.95), an enzyme concentrated in plasma

Does bilirubin protect against developing diabetes mellitus?

Science.gov (United States)

Breimer, Lars H; Mikhailidis, Dimitri P

2016-01-01

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

Bilirubin bound to cells does not form photoisomers

International Nuclear Information System (INIS)

Christensen, T.; Kinn, G.

1993-01-01

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

Bilirubin Blood Test: MedlinePlus Lab Test Information

Science.gov (United States)

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

The triplet excited state of bilirubin

International Nuclear Information System (INIS)

Land, E.J.

1976-01-01

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

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

International Nuclear Information System (INIS)

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

2004-01-01

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

Serum bilirubin and the risk of rheumatoid arthritis.

Science.gov (United States)

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

2017-11-01

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

Animal pigment bilirubin discovered in plants.

Science.gov (United States)

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

2009-03-04

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

Supramolecular Complexes Formed in Systems Bile Salt-Bilirubin-Silica

Science.gov (United States)

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

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

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

DEFF Research Database (Denmark)

Honoré, B

1987-01-01

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

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

Science.gov (United States)

Ahlfors, Charles E

2016-10-01

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

Bilirubin and Stroke Risk Using a Mendelian Randomization Design.

Science.gov (United States)

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

2017-05-01

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

Bilirubin and its oxidation products damage brain white matter

Science.gov (United States)

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

2014-01-01

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

Pulse radiolysis of bilirubin in aqueous solution

International Nuclear Information System (INIS)

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

1977-01-01

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

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

NARCIS (Netherlands)

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

1984-01-01

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

Bilirubin adsorption on nanocrystalline titania films

International Nuclear Information System (INIS)

Yang Zhengpeng; Si Shihui; Fung Yingsing

2007-01-01

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

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

International Nuclear Information System (INIS)

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

1994-01-01

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

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

Science.gov (United States)

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

2014-02-01

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

Trans-Cutaneous Bilirubinometery versus Serum Bilirubin in Neonatal Jaundice.

Science.gov (United States)

Mahram, Manoochehr; Oveisi, Sonia; Jaberi, Najmeh

2015-12-01

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

Comparison of serum bilirubin estimation with transcutaneous bilirubinometry in neonates

International Nuclear Information System (INIS)

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

2010-01-01

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

A new infectious encephalopathy syndrome, clinically mild encephalopathy associated with excitotoxicity (MEEX).

Science.gov (United States)

Hirai, Nozomi; Yoshimaru, Daisuke; Moriyama, Yoko; Yasukawa, Kumi; Takanashi, Jun-Ichi

2017-09-15

Acute infectious encephalopathy is often observed in children in East Asia including Japan. More than 40% of the patients remain unclassified into specific syndromes. To investigate the underlying pathomechanisms in those with unclassified encephalopathy, we evaluated brain metabolism by MR spectroscopy. Among seven patients with acute encephalopathy admitted to our hospital from June 2016 to May 2017, three were classified into acute encephalopathy with biphasic seizures and late reduced diffusion (AESD). The other four showed consciousness disturbance lasting more than three days with no parenchymal lesion visible on MRI, which led to a diagnosis of unclassified encephalopathy. MR spectroscopy in these four patients, however, revealed an increase of glutamine with a normal N-acetyl aspartate level on days 5 to 8, which had normalized by follow-up studies on days 11 to 16. The four patients clinically recovered completely. Among 27 patients with encephalopathy, including the present seven patients, admitted to our hospital from January 2015 to March 2017, seven (26%) were classified into this type, which we propose is a new encephalopathy syndrome, clinically mild encephalopathy associated with excitotoxicity (MEEX). MEEX is the second most common subtype, following AESD (30%). This study suggests that excitotoxicity may be a common underlying pathomechanism of acute infectious encephalopathy, and prompt astrocytic neuroprotection from excitotoxicity may prevent progression of MEEX into AESD. Copyright © 2017 Elsevier B.V. All rights reserved.

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

Science.gov (United States)

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

2002-10-01

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

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

Science.gov (United States)

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

2018-02-06

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

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

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

2016-01-01

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

Hepatocyte cotransport of taurocholate and bilirubin glucuronides: Role of microtubules

International Nuclear Information System (INIS)

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

1988-01-01

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

Hepatic Encephalopathy

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Full Text Available ... OVERVIEW Donate Now Join an Event Volunteer Your Time The Legacy Society Make Gifts of Stock Donate ... problem from liver disease that gets worse over time. Hepatic Encephalopathy, sometimes referred to as portosystemic encephalopathy ...

Hepatic Encephalopathy

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Full Text Available ... Now Hepatic Encephalopathy Back Hepatic Encephalopathy is a brain disorder that develops in some individuals with liver ... is a condition that causes temporary worsening of brain function in people with advanced liver disease. When ...

Hepatic Encephalopathy

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Full Text Available ... that can be corrected . It may also occur as part of a chronic problem from liver disease ... worse over time. Hepatic Encephalopathy, sometimes referred to as portosystemic encephalopathy or PSE, is a condition that ...

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

Science.gov (United States)

2010-04-01

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

Hepatic Encephalopathy

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Full Text Available ... Disease Type 1 (von Gierke) Hemochromatosis Hepatic Encephalopathy Hepatitis A Hepatitis B Hepatitis C Intrahepatic Cholestasis of Pregnancy ( ... Disease Type 1 (von Gierke) Hemochromatosis Hepatic Encephalopathy Hepatitis A Hepatitis B Hepatitis C Intrahepatic Cholestasis of Pregnancy ( ...

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

DEFF Research Database (Denmark)

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

2013-01-01

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

Anti-Genotoxic Potential of Bilirubin In Vivo

DEFF Research Database (Denmark)

Wallner, Marlies; Antl, Nadja; Rittmannsberger, Barbara

2013-01-01

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

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

NARCIS (Netherlands)

Jansen, P. L.

1981-01-01

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

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

NARCIS (Netherlands)

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

1977-01-01

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

Conjugated Bilirubin Triggers Anemia by Inducing Erythrocyte Death

Science.gov (United States)

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

2015-01-01

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

Recent advances in the management of neonatal jaundice

Directory of Open Access Journals (Sweden)

Watchko JF

2014-11-01

Full Text Available Jon F Watchko Division of Newborn Medicine, Department of Pediatrics, University of Pittsburgh School of Medicine, Magee-Womens Research Institute, Pittsburgh, PA, USA Abstract: Advances in the clinical assessment strategies used to identify neonates at risk for the development of severe hyperbilirubinemia and bilirubin neurotoxicity, as well as the treatment measures to control hyperbilirubinemia in newborns, continue to be made. They include, among others, universal predischarge birth hospitalization bilirubin screening, the confirmation that hemolysis is an important risk factor for bilirubin neurotoxicity, the use of a numeric scoring system to help stage the severity of acute bilirubin encephalopathy, the potential advantages of turquoise-light phototherapy, and the potential role of heme-oxygenase inhibitors in preventing the need for exchange transfusions, all of which are reviewed here. Keywords: phototherapy, exchange transfusion, bilirubin, free bilirubin, bilirubin encephalopathy, kernicterus

Pathogenesis of Hepatic Encephalopathy

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Irena Ciećko-Michalska

2012-01-01

Full Text Available Hepatic encephalopathy can be a serious complication of acute liver failure and chronic liver diseases, predominantly liver cirrhosis. Hyperammonemia plays the most important role in the pathogenesis of hepatic encephalopathy. The brain-blood barrier disturbances, changes in neurotransmission, neuroinflammation, oxidative stress, GABA-ergic or benzodiazepine pathway abnormalities, manganese neurotoxicity, brain energetic disturbances, and brain blood flow abnormalities are considered to be involved in the development of hepatic encephalopathy. The influence of small intestine bacterial overgrowth (SIBO on the induction of minimal hepatic encephalopathy is recently emphasized. The aim of this paper is to present the current views on the pathogenesis of hepatic encephalopathy.

Pathogenesis of Hepatic Encephalopathy

Science.gov (United States)

Ciećko-Michalska, Irena; Szczepanek, Małgorzata; Słowik, Agnieszka; Mach, Tomasz

2012-01-01

Hepatic encephalopathy can be a serious complication of acute liver failure and chronic liver diseases, predominantly liver cirrhosis. Hyperammonemia plays the most important role in the pathogenesis of hepatic encephalopathy. The brain-blood barrier disturbances, changes in neurotransmission, neuroinflammation, oxidative stress, GABA-ergic or benzodiazepine pathway abnormalities, manganese neurotoxicity, brain energetic disturbances, and brain blood flow abnormalities are considered to be involved in the development of hepatic encephalopathy. The influence of small intestine bacterial overgrowth (SIBO) on the induction of minimal hepatic encephalopathy is recently emphasized. The aim of this paper is to present the current views on the pathogenesis of hepatic encephalopathy. PMID:23316223

UDP-glucuronyltransferase-catalyzed deconjugation of bilirubin monoglucuronide

NARCIS (Netherlands)

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

1984-01-01

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

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

Science.gov (United States)

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

2014-08-01

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

Acute Alcohol Consumption Elevates Serum Bilirubin, an Endogenous Antioxidant

Science.gov (United States)

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

2015-01-01

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

Preliminary development of a fiber optic sensor for measuring bilirubin.

Science.gov (United States)

Babin, Steven M; Sova, Raymond M

2014-01-01

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

Dopaminergic agonists for hepatic encephalopathy

DEFF Research Database (Denmark)

Als-Nielsen, B; Gluud, L L; Gluud, C

2004-01-01

Hepatic encephalopathy may be associated with an impairment of the dopaminergic neurotransmission. Dopaminergic agonists may therefore have a beneficial effect on patients with hepatic encephalopathy.......Hepatic encephalopathy may be associated with an impairment of the dopaminergic neurotransmission. Dopaminergic agonists may therefore have a beneficial effect on patients with hepatic encephalopathy....

Prognostic significance of serum bilirubin in stroke

International Nuclear Information System (INIS)

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

2011-01-01

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

Newborn jaundice - discharge

Science.gov (United States)

... Biliary atresia Bili lights Bilirubin blood test Bilirubin encephalopathy Exchange transfusion Jaundice and breastfeeding Newborn jaundice Premature infant Rh incompatibility Patient Instructions Newborn ...

Preliminary Development of a Fiber Optic Sensor for Measuring Bilirubin

Directory of Open Access Journals (Sweden)

Steven M. Babin

2014-01-01

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

Membrane Transporters for Bilirubin and Its Conjugates: A Systematic Review

Directory of Open Access Journals (Sweden)

Jovana Čvorović

2017-12-01

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

MRI of neonatal encephalopathy

International Nuclear Information System (INIS)

Khong, P.L.; Lam, B.C.C.; Tung, H.K.S.; Wong, V.; Chan, F.L.; Ooi, G.C.

2003-01-01

We present the magnetic resonance imaging (MRI) findings in neonatal encephalopathy, including hypoxic-ischaemic encephalopathy, perinatal/neonatal stroke, metabolic encephalopathy from inborn errors of metabolism, congenital central nervous system infections and birth trauma. The applications of advanced MRI techniques, such as diffusion-weighted imaging and magnetic resonance spectroscopy are emphasized

Reduced total serum bilirubin levels are associated with ulcerative colitis.

Directory of Open Access Journals (Sweden)

Kathleen M Schieffer

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

Metabolism of bilirubin by human cytochrome P450 2A6

Energy Technology Data Exchange (ETDEWEB)

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

2012-05-15

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

Metabolism of bilirubin by human cytochrome P450 2A6

International Nuclear Information System (INIS)

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

2012-01-01

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

Case of hepatic encephalopathy induced by thortrast

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Shirato, H.; Kudo, N.; Takita, K. (Nakatori Hospital, Akita (Japan))

1980-09-01

A case of hepatic encephalopathy induced by thorotrast injected as a contrast 40 years before was reported. The patient was a 64-year-old man with severe liver dysfunction, and had psychic and neurological symptoms, and hyperammonemia. There was a relationship between ammonium concentration in blood and psychic and neurological symptoms. Electroencephalogram showed three phases waves peculiar to hepatic coma intermittently. Thorotrast in the liver was detected by radiological methods and in vivo measurement of the radioactivity. From the above-mentioned result, this disease was diagnosed as hepatic encephalopathy induced by long-term sedimentation of thorotrast without complication of malignant tumors. Because of the concurrent presence of cerebral infarction, the diagnosis was difficult to make.

Treatment of Epileptic Encephalopathies.

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Balestrini, Simona; Sisodiya, Sanjay M

2017-01-01

Epileptic encephalopathies represent the most severe epilepsies, with onset in infancy and childhood and seizures continuing in adulthood in most cases. New genetic causes are being identified at a rapid rate. Treatment is challenging and the overall outcome remains poor. Available targeted treatments, based on the precision medicine approach, are currently few. To provide an overview of the treatment of epileptic encephalopathies with known genetic determinants, including established treatment, anecdotal reports of specific treatment, and potential tailored precision medicine strategies. Genes known to be associated to epileptic encephalopathy were selected. Genes where the association was uncertain or with no reports of details on treatment, were not included. Although some of the genes included are associated with multiple epilepsy phenotypes or other organ involvement, we have mainly focused on the epileptic encephalopathies and their antiepileptic treatments. Most epileptic encephalopathies show genotypic and phenotypic heterogeneity. The treatment of seizures is difficult in most cases. The available evidence may provide some guidance for treatment: for example, ACTH seems to be effective in controlling infantile spams in a number of genetic epileptic encephalopathies. There are potentially effective tailored precision medicine strategies available for some of the encephalopathies, and therapies with currently unexplained effectiveness in others. Understanding the effect of the mutation is crucial for targeted treatment. There is a broad range of disease mechanisms underlying epileptic encephalopathies, and this makes the application of targeted treatments challenging. However, there is evidence that tailored treatment could significantly improve epilepsy treatment and prognosis. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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

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

2016-02-01

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

Revalidation and rationale for high pKa values of unconjugated bilirubin

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Ostrow J Donald

2007-05-01

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

PPARα: A Master Regulator of Bilirubin Homeostasis

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Cyril Bigo

2014-01-01

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

The Levels Of Cytokines And S 100β Which Associated With The Pathogenesis Of Hepatic Encephalopathy In Rats: Role Of Lactulose And N-Acetylcysteine In Its Treatment

International Nuclear Information System (INIS)

Heibashy, M.I.A.; Mazen, G.M.A.; Ibrahim, M.A.

2012-01-01

Hepatic encephalopathy (HE) is a reversible syndrome of impaired brain function occurring in patients with advanced liver failure. Recently, it has been reported that pro inflammatory cytokines are involved in the pathogenesis of brain oedema during HE. This study was conducted to elucidate the changes of plasma and brain pro inflammatory cytokines in encephalopathy rats and to evaluate the hepato-protective activity of lactulose or N-acetylcysteine against thioacetamide (TAA) induced hepatopathy in rats. Acute hepatic encephalopathy (HE) in rats was induced by intraperitoneal injection of thioacetamide in 24 hours intervals for two consecutive days. The obtained results revealed significant increase (P<0.05) in liver function tests (ALT, AST, ALP, bilirubin), ammonia, nitric oxide and total oxidant capacity (TOC) in TAA rats than those in control ones. Brain water content was significantly elevated in TAA rats as compared with the control. In addition, the levels of pro inflammatory cytokines (IL-1Β, IL-6, TNF-α) in both serum and brain were significantly increased associated with a remarkable elevation in the level of serum S 100β in TAA rats. On the other hand, induction of hepatic encephalopathy caused significant decrease (P<0.05) in total antioxidant capacity (TAC) levels. When HE rats group was treated with lactulose or N-acetylcysteine, considerable amelioration effects in all previous studied parameters were pronounced dependent on certain mechanisms

Influence of hemoglobin on non-invasive optical bilirubin sensing

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

2012-03-01

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

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

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

2015-01-01

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

Enterohepatic circulation of nonconjugated bilirubin in rats fed with human milk

International Nuclear Information System (INIS)

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

1991-01-01

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

A case of hepatic encephalopathy induced by trotrast

International Nuclear Information System (INIS)

Shirato, Hideo; Kudo, Norishige; Takita, Kyoji

1980-01-01

A case of hepatic encephalopathy induced by thorotrast injected as a contrast 40 years before was reported. The patient was a 64-year-old man with severe liver dysfunction, and had psychic and neurological symptoms, and hyperammonemia. There was a relationship between ammonium concentration in blood and psychic and neurological symptoms. Electroencephalogram showed three phases waves peculiar to hepatic coma intermittently. Throtrast in the liver was detected by radiological methods and in vivo measurement of the radioactivity. From the above-mentioned result, this disease was diagnosed as hepatic encephalopathy induced by long-term sedimentation of thorotrast without complication of malignant tumors. Because of the concurrent presence of cerebral infarction, the diagnosis was difficult to make. (Tsunoda, M.)

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

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

2016-10-01

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

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

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

2011-01-01

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

Bilirubin nanoparticle preconditioning protects against hepatic ischemia-reperfusion injury.

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

2017-07-01

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

The kinetics of oxidation of bilirubin and ascorbic acid in solution

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

2012-07-01

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

Prognostic factors for acute encephalopathy with bright tree appearance.

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Azuma, Junji; Nabatame, Shin; Nakano, Sayaka; Iwatani, Yoshiko; Kitai, Yukihiro; Tominaga, Koji; Kagitani-Shimono, Kuriko; Okinaga, Takeshi; Yamamoto, Takehisa; Nagai, Toshisaburo; Ozono, Keiichi

2015-02-01

To determine the prognostic factors for encephalopathy with bright tree appearance (BTA) in the acute phase through retrospective case evaluation. We recruited 10 children with encephalopathy who presented with BTA and classified them into 2 groups. Six patients with evident regression and severe psychomotor developmental delay after encephalopathy were included in the severe group, while the remaining 4 patients with mild mental retardation were included in the mild group. We retrospectively analyzed their clinical symptoms, laboratory data, and magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) findings. Patients in the severe group developed subsequent complications such as epilepsy and severe motor impairment. Univariate analysis revealed that higher maximum lactate dehydrogenase (LDH) levels (p=0.055) were a weak predictor of poor outcome. Maximum creatinine levels were significantly higher (p<0.05) and minimal platelet counts were significantly lower (p<0.05) in the severe group than in the mild group. Acute renal failure was not observed in any patient throughout the study. MRS of the BTA lesion during the BTA period showed elevated lactate levels in 5 children in the severe group and 1 child in the mild group. MRI performed during the chronic phase revealed severe brain atrophy in all patients in the severe group. Higher creatinine and LDH levels and lower platelet counts in the acute phase correlated with poor prognosis. Increased lactate levels in the BTA lesion during the BTA period on MRS may predict severe physical and mental disability. Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Management and investigation of neonatal encephalopathy: 2017 update

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Martinello, Kathryn; Hart, Anthony R; Yap, Sufin; Mitra, Subhabrata

2017-01-01

This review discusses an approach to determining the cause of neonatal encephalopathy, as well as current evidence on resuscitation and subsequent management of hypoxic-ischaemic encephalopathy (HIE). Encephalopathy in neonates can be due to varied aetiologies in addition to hypoxic-ischaemia. A combination of careful history, examination and the judicious use of investigations can help determine the cause. Over the last 7 years, infants with moderate to severe HIE have benefited from the introduction of routine therapeutic hypothermia; the number needed to treat for an additional beneficial outcome is 7 (95% CI 5 to 10). More recent research has focused on optimal resuscitation practices for babies with cardiorespiratory depression, such as delayed cord clamping after establishment of ventilation and resuscitation in air. Around a quarter of infants with asystole at 10 min after birth who are subsequently cooled have normal outcomes, suggesting that individualised decision making on stopping resuscitation is needed, based on access to intensive treatment unit and early cooling. The full benefit of cooling appears to have been exploited in our current treatment protocols of 72 hours at 33.5°C; deeper and longer cooling showed adverse outcome. The challenge over the next 5–10 years will be to assess which adjunct therapies are safe and optimise hypothermic brain protection in phase I and phase II trials. Optimal care may require tailoring treatments according to gender, genetic risk, injury severity and inflammatory status. PMID:28389438

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

International Nuclear Information System (INIS)

Cao Rongzhen; Dong Mo; Zhang Yulong; Zhou Ruiju

1996-01-01

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

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

Science.gov (United States)

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

1985-11-01

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

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

NARCIS (Netherlands)

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

2004-01-01

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

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

Science.gov (United States)

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

2015-01-01

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

Benzodiazepine receptor antagonists for hepatic encephalopathy

DEFF Research Database (Denmark)

Als-Nielsen, B; Gluud, L L; Gluud, C

2004-01-01

Hepatic encephalopathy may be associated with accumulation of substances that bind to a receptor-complex in the brain resulting in neural inhibition. Benzodiazepine receptor antagonists may have a beneficial effect on patients with hepatic encephalopathy.......Hepatic encephalopathy may be associated with accumulation of substances that bind to a receptor-complex in the brain resulting in neural inhibition. Benzodiazepine receptor antagonists may have a beneficial effect on patients with hepatic encephalopathy....

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

Directory of Open Access Journals (Sweden)

Dora eBrites

2012-05-01

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

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

Science.gov (United States)

2010-04-01

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

Subcortical arteriosclerotic encephalopathy (Binswanger disease)

International Nuclear Information System (INIS)

Settanni, F.; Dumont, P.; Casella, C.L.; Pascuzzi, L.; Cecilio, S.; Caldas, J.G.

1992-01-01

Four patients with variable clinical and tomographic features were diagnosed as having subcortical arteriosclerotic encephalopathy (Binswanger disease). This diagnosis was done based on the presence of subacute progression of focal cerebral deficits, presence of hypertension, systemic vascular disease and dementia. The pathogenesis of subcortical arteriosclerotic encephalopathy is unknown; possible mechanism include diffuse ischemia and fluid transudation with subsequent gliosis related to subacute hypertensive encephalopathy. (author)

Antioxidant mechanism of bilirubin: both HAT and SET are possible

International Nuclear Information System (INIS)

Adhikari, Soumyakanti; Joshi, Ravi; Mukherjee, Tulsi

2008-01-01

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

Reversible MRI abnormalities in an unusual paediatric presentation of Wernicke's encephalopathy

International Nuclear Information System (INIS)

Sparacia, G.; Banco, A.; Lagalla, R.

1999-01-01

Background. We report an unusual paediatric presentation of acute Wernicke's encephalopathy in a 12-year-old boy affected by chronic gastrointestinal disease. MRI demonstrated, in addition to the typical diencephalic and mesencephalic signal abnormalities on T2-weighted images, enhancement of the mammillary bodies and the floor of the hypothalamus. Materials and methods. Following parenteral administration of thiamine for 4 days, the patient recovered from his neurological deficits and on follow-up enhanced MRI 1 month later, no signal abnormalities were found nor was there diencephalic or mesencephalic atrophy, as is usual in the chronic phase of the disease. Results. MRI provides crucial information in the diagnosis of Wernicke's encephalopathy, either in the acute or chronic phases of the disease. Conclusion. Our report provides an additional clue for recognition of the acute phase of the disease; enhancement of the floor of the hypothalamus has not previously been described despite its recorded involvement at autopsy. (orig.)

CDKL5 gene-related epileptic encephalopathy: electroclinical findings in the first year of life.

Science.gov (United States)

Melani, Federico; Mei, Davide; Pisano, Tiziana; Savasta, Salvatore; Franzoni, Emilio; Ferrari, Anna Rita; Marini, Carla; Guerrini, Renzo

2011-04-01

Cyclin-dependent kinase-like 5 (CDKL5) gene abnormalities cause an early-onset epileptic encephalopathy. We performed video-electroencephalography (video-EEG) monitoring early in the course of CDKL5-related epileptic encephalopathy in order to examine the early electroclinical characteristics of the condition. We used video-EEG to monitor six infants (five females, one male) with CDKL5-related epileptic encephalopathy (five mutations; one deletion), at ages 45 days to 12 months and followed them up to the ages of 14 months to 5 years (mean age 23 mo). We focused our analysis on the first year of life. The results were evaluated against those of a comparison group of nine infants (aged below 1y) with epileptic encephalography who had tested negative for CDKL5 mutations and deletions. One infant exhibited normal background activity, three exhibited moderate slowing, and two exhibited a suppression burst pattern. Two participants had epileptic spasms and four had a stereotyped complex seizure pattern, which we defined as a 'prolonged' generalized tonic-clonic event consisting of a tonic-tonic/vibratory contraction, followed by a clonic phase with series of spasms, gradually translating into repetitive distal myoclonic jerks. Seizure duration ranged from 2 to 4 minutes. The EEG correlate of each clinical phase included an initial electrodecremental event (tonic vibratory phase), irregular series of sharp waves and spike slow waves (clonic phase with series of spasms), and bilateral rhythmic sharp waves (time locked with myoclonus). Infants with CDKL5-related early epileptic encephalopathy can present in the first year of life with an unusual electroclinical pattern of 'prolonged' generalized tonic-clonic seizures. © The Authors. Journal compilation © Mac Keith Press 2011.

Unconjugated free bilirubin in preterm infants.

Science.gov (United States)

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

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

Recent advances in hepatic encephalopathy

Science.gov (United States)

DeMorrow, Sharon

2017-01-01

Hepatic encephalopathy describes the array of neurological alterations that occur during acute liver failure or chronic liver injury. While key players in the pathogenesis of hepatic encephalopathy, such as increases in brain ammonia, alterations in neurosteroid levels, and neuroinflammation, have been identified, there is still a paucity in our knowledge of the precise pathogenic mechanism. This review gives a brief overview of our understanding of the pathogenesis of hepatic encephalopathy and then summarizes the significant recent advances made in clinical and basic research contributing to our understanding, diagnosis, and possible treatment of hepatic encephalopathy. A literature search using the PubMed database was conducted in May 2017 using “hepatic encephalopathy” as a keyword, and selected manuscripts were limited to those research articles published since May 2014. While the authors acknowledge that many significant advances have been made in the understanding of hepatic encephalopathy prior to May 2014, we have limited the scope of this review to the previous three years only. PMID:29026534

Determination of cholesterol, calcium carbonate and bilirubinate of gallstone

International Nuclear Information System (INIS)

Iqbal, Y.; Nazneen, B.I.

2004-01-01

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

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

African Journals Online (AJOL)

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

Genetic disorders associated with neonatal jaundice

OpenAIRE

Morioka, Ichiro; Morikawa, Satoru; Yusoff, Surini; Harahap, Indra Sari Kusuma; Nishimura, Noriyuki; Yokoyama, Naoki; Matsuo, Masafumi; Rostenberghe, Hans Van; Nishio, Hisahide

2013-01-01

Abstract. Neonatal jaundice is very common in newborn infants. Although it is often a natural and transitional condition, some infants develop severe hyperbilirubinemia, in which unconjugated bilirubin in the serum may cross the blood-brain-barrier and cause bilirubin encephalopathy (acute bilirubin intoxication) or kernicterus (chronic bilirubin intoxication). To avoid these hazardous conditions, it is important to identify the infants at risk for developing severe hyperbilirubinemia. There ...

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

Science.gov (United States)

Hamza, Mostafa; Hamza, Mohammad

1988-06-01

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

Rifaximin in the treatment of hepatic encephalopathy

Directory of Open Access Journals (Sweden)

Iadevaia MD

2011-12-01

Full Text Available Maddalena Diana Iadevaia, Anna Del Prete, Claudia Cesaro, Laura Gaeta, Claudio Zulli, Carmelina LoguercioDepartment of Internistica Clinica e Sperimentale, F Magrassi e A Lanzara, Hepatogastroenterology Unit, Second University of Naples, Naples, ItalyAbstract: Hepatic encephalopathy is a challenging complication in patients with advanced liver disease. It can be defined as a neuropsychiatric syndrome caused by portosystemic venous shunting, ranging from minimal to overt hepatic encephalopathy or coma. Its pathophysiology is still unclear, although increased levels of ammonia play a key role. Diagnosis of hepatic encephalopathy is currently based on specific tests evaluating the neuropsychiatric state of patients and their quality of life; the severity of hepatic encephalopathy is measured by the West Haven criteria. Treatment of hepatic encephalopathy consists of pharmacological and corrective measures, as well as nutritional interventions. Rifaximin received approval for the treatment of hepatic encephalopathy in 2010 because of its few side effects and pharmacological benefits. The aim of this work is to review the use and efficacy of rifaximin both in acute and long-term management of hepatic encephalopathy. Treatment of overt hepatic encephalopathy involves management of the acute episode as well as maintenance of remission in those patients who have previously experienced an episode, in order to improve their quality of life. The positive effect of rifaximin in reducing health care costs is also discussed.Keywords: acute hepatic encephalopathy, recurrent hepatic encephalopathy, rifaximin, lactulose, cost, health-related quality of life

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

Science.gov (United States)

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

2017-01-01

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

Bilirubin Albumin Binding and Unbound Unconjugated Hyperbilirubinemia in Premature Infants.

Science.gov (United States)

Amin, Sanjiv B; Wang, Hongyue

2018-01-01

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

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

Science.gov (United States)

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

2016-01-01

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

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

NARCIS (Netherlands)

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

1994-01-01

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

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

Science.gov (United States)

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

2016-11-01

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

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

International Nuclear Information System (INIS)

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

1982-01-01

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

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

Science.gov (United States)

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

2017-01-01

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

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

Science.gov (United States)

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

2016-11-01

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

Moderate Unconjugated Hyperbilirubinemia Causes a Transient but Delayed Suppression of Amplitude-Integrated Electroencephalographic Activity in Preterm Infants

NARCIS (Netherlands)

ter Horst, Hendrik J.; Bos, Arend F.; Duijvendijk, Jildou; Hulzebos, Christian V.

2012-01-01

Background: Unconjugated hyperbilirubinemia occurs frequently in preterm infants and may result in bilirubin encephalopathy. Amplitude-integrated electroencephalography (aEEG) is used to evaluate brain function in newborns. Objectives: To investigate the influence of total serum bilirubin (TSB) on

Branched-chain amino acids for hepatic encephalopathy

DEFF Research Database (Denmark)

Als-Nielsen, B; Koretz, R L; Kjaergard, L L

2003-01-01

Hepatic encephalopathy may be caused by a decreased plasma ratio of branched-chain amino acids (BCAA) to aromatic amino acids. Treatment with BCAA may therefore have a beneficial effect on patients with hepatic encephalopathy.......Hepatic encephalopathy may be caused by a decreased plasma ratio of branched-chain amino acids (BCAA) to aromatic amino acids. Treatment with BCAA may therefore have a beneficial effect on patients with hepatic encephalopathy....

An unusual cause of anemia and encephalopathy

Directory of Open Access Journals (Sweden)

Sanjeev Kumar Sharma

2015-04-01

Full Text Available The authors present here an interesting case of recent onset anemia that was associated with an encephalopathy of the unusual cause.Although severe anemia can theoretically result in anemic hypoxia and can then lead to hypoxic encephalopathy, it is not a primary cause of encephalopathy. More frequently anemia can contribute together with other multiple causes of encephalopathy, such as infections, metabolic abnormalities, trauma, hepatic dysfunction, hypertension, toxins.

Dopamine agents for hepatic encephalopathy

DEFF Research Database (Denmark)

Junker, Anders Ellekær; Als-Nielsen, Bodil; Gluud, Christian

2014-01-01

BACKGROUND: Patients with hepatic encephalopathy may present with extrapyramidal symptoms and changes in basal ganglia. These changes are similar to those seen in patients with Parkinson's disease. Dopamine agents (such as bromocriptine and levodopa, used for patients with Parkinson's disease) have...... therefore been assessed as a potential treatment for patients with hepatic encephalopathy. OBJECTIVES: To evaluate the beneficial and harmful effects of dopamine agents versus placebo or no intervention for patients with hepatic encephalopathy. SEARCH METHODS: Trials were identified through the Cochrane...... hepatic encephalopathy that were published during 1979 to 1982 were included. Three trials assessed levodopa, and two trials assessed bromocriptine. The mean daily dose was 4 grams for levodopa and 15 grams for bromocriptine. The median duration of treatment was 14 days (range seven to 56 days). None...

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

Science.gov (United States)

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

2014-01-01

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

Genetically elevated bilirubin and risk of ischaemic heart disease

DEFF Research Database (Denmark)

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

2013-01-01

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

False high level in total bilirubin estimation in nonicteric serum

African Journals Online (AJOL)

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

[Hashimoto's encephalopathy and autoantibodies].

Science.gov (United States)

Yoneda, Makoto

2013-04-01

Encephalopathy occasionally occurs in association with thyroid disorders, but most of these are treatable. These encephalopathies include a neuropsychiatric disorder associated with hypothyroidism, called myxedema encephalopathy. Moreover, Hashimoto's encephalopathy (HE) has been recognized as a new clinical disease based on an autoimmune mechanism associated with Hashimoto's thyroiditis. Steroid treatment was successfully administered to these patients. Recently, we discovered that the serum autoantibodies against the NH2-terminal of α-enolase (NAE) are highly specific diagnostic biomarkers for HE. Further, we analyzed serum anti-NAE autoantibodies and the clinical features in many cases of HE from institutions throughout Japan and other countries. Approximately half of assessed HE patients carry anti-NAE antibodies. The age was widely distributed with 2 peaks (20-30 years and 50-70 years). Most HE patients were in euthyroid states, and all patients had anti-thyroid (TG) antibodies and anti-thyroid peroxidase (TPO) antibodies. Anti-TSH receptor (TSH-R) antibodies were observed in some cases. The common neuropsychiatry features are consciousness disturbance and psychosis, followed by cognitive dysfunction, involuntary movements, seizures, and ataxia. Abnormalities on electroencephalography (EEG) and decreased cerebral blood flow on brain SPECT were common findings, whereas abnormal findings on brain magnetic resonance imaging (MRI) were rare. HE patients have various clinical phenotypes such as the acute encephalopathy form, the chronic psychiatric form, and other particular clinical forms, including limbic encephalitis, progressive cerebellar ataxia, and Creutzfeldt-Jakob disease (CJD)-like form. The cerebellar ataxic form of HE clinically mimics spinocerebellar degeneration (SCD) and is characterized by the absence of nystagmus, absent or mild cerebellar atrophy, and lazy background activities on EEG. Taken together, these data suggest that the possibility of

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

Directory of Open Access Journals (Sweden)

Charalambos Neocleous

2014-01-01

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

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

International Nuclear Information System (INIS)

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

1986-01-01

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

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

NARCIS (Netherlands)

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

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

Screening of subclinical hepatic encephalopathy

NARCIS (Netherlands)

Groeneweg, M; Moerland, W; Quero, J C; Hop, W C; Krabbe, P F; Schalm, S W

BACKGROUND/AIMS: Subclinical hepatic encephalopathy adversely affects daily functioning. The aim of this study was to determine which elements of daily life have predictive value for subclinical hepatic encephalopathy. METHODS: The study was performed in 179 outpatients with liver cirrhosis.

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

NARCIS (Netherlands)

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

1977-01-01

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

Diagnostic value of conventional MRI combined with DTI for neonatal hyperbilirubinemia

Directory of Open Access Journals (Sweden)

Ruifang Yan

2018-04-01

Full Text Available Background: Neonatal hyperbilirubinemia (NHB is a common clinical disease and can cause bilirubin encephalopathy in severe cases. It is now widely accepted that increased signal intensity in the globus pallidus on MR T1WI is an important sign of neonatal bilirubin encephalopathy. And brain diffusion tensor imaging (DTI has not been used extensively to study hyperbilirubinemia (HB. So we compared newborns with different hyperbilirubinemia of different severities and healthy newborns in order to determine the relationships among MRI signal intensities, serum bilirubin levels, and the molecular changes in brain water diffusion in hyperbilirubinemia. Methods: Seventy-three newborns with hyperbilirubinemia were grouped into three groups: the mild increase group (M, 27 cases, the moderate increase group (O, 28 cases, and the severe group (S, 18 cases. The groups were based on serum bilirubin levels. We performed cranial MRI in these newborns, as well as 29 healthy full-term infants (group N. We compared and analyzed the mean signal values for the globus pallidus and the relationship between the bilirubin level and the score on the neonatal behavioral neurological assessment. Fifteen, 10, and 10 patients in groups M, O + S, and N were successfully examined using diffusion tensor imaging (DTI. We assessed the relationships among the signal from the globus pallidus, fractional anisotropy (FA, and average diffusion coefficient (DCav of the posterior limb of the internal capsule (PLIC. Results: There were significant differences in the mean signal value of bilateral globus pallidus between group O/S and group N [p = 0.029 and 0.000 (left, 0.038 and 0.000 (right]. There were no significant differences in bilateral FA or DCav values between the patient groups and group N. The bilateral PLIC-FA and DCav values were significantly different between the patient groups and group N (P = 0.014 and 0.047, respectively. Conclusions: Increased signal intensity

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

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

2015-12-01

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

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

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Taban Sadeghi Mohammadreza

2015-10-01

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

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

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

2018-01-01

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

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

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

2010-11-01

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

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

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

2017-10-01

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

Hepatic Encephalopathy

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Hashimoto's encephalopathy : epidemiology, pathogenesis and management.

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Mocellin, Ramon; Walterfang, Mark; Velakoulis, Dennis

2007-01-01

Hashimoto's encephalopathy is a term used to describe an encephalopathy of presumed autoimmune origin characterised by high titres of antithyroid peroxidase antibodies. In a similar fashion to autoimmune thyroid disease, Hashimoto's encephalopathy is more common in women than in men. It has been reported in paediatric, adult and elderly populations throughout the world. The clinical presentation may involve a relapsing and remitting course and include seizures, stroke-like episodes, cognitive decline, neuropsychiatric symptoms and myoclonus. Thyroid function is usually clinically and biochemically normal.Hashimoto's encephalopathy appears to be a rare disorder, but, as it is responsive to treatment with corticosteroids, it must be considered in cases of 'investigation negative encephalopathies'. Diagnosis is made in the first instance by excluding other toxic, metabolic and infectious causes of encephalopathy with neuroimaging and CSF examination. Neuroimaging findings are often not helpful in clarifying the diagnosis. Common differential diagnoses when these conditions are excluded are Creutzfeldt-Jakob disease, rapidly progressive dementias, and paraneoplastic and nonparaneoplastic limbic encephalitis. In the context of the typical clinical picture, high titres of antithyroid antibodies, in particular antithyroid peroxidase antibodies, are diagnostic. These antibodies, however, can be detected in elevated titres in the healthy general population. Treatment with corticosteroids is almost always successful, although relapse may occur if this treatment is ceased abruptly. Other forms of immunomodulation, such as intravenous immune-globulin and plasma exchange, may also be effective. Despite the link to autoimmune thyroid disease, the aetiology of Hashimoto's encephalopathy is unknown. It is likely that antithyroid antibodies are not pathogenic, but titres can be a marker of treatment response. Pathological findings can suggest an inflammatory process, but features

Increased conjugated bilirubin is sufficient to initiate screening for biliary atresia

DEFF Research Database (Denmark)

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

2015-01-01

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

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

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

2017-01-01

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

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

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

2016-01-01

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

[Star fruit (Averrhoa carambola) toxic encephalopathy].

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Signaté, A; Olindo, S; Chausson, N; Cassinoto, C; Edimo Nana, M; Saint Vil, M; Cabre, P; Smadja, D

2009-03-01

Ingestion of star fruit (Averrhoa carambola) can induce severe intoxication in subjects with chronic renal failure. Oxalate plays a key role in the neurotoxicity of star fruit. We report the cases of two patients with unknown chronic renal insufficiency who developed severe encephalopathy after ingestion of star fruit. The two patients developed intractable hiccups, vomiting, impaired consciousness and status epilepticus. Diffusion-weighted MR imaging showed cortical and thalamic hyperintense lesions related to epileptic status. They improved after being submitted to continuous hemofiltration which constitutes the most effective treatment during the acute phase.

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

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Kunutsor, Setor K

2015-12-01

Observational epidemiological evidence supports a linear inverse and independent association between serum total bilirubin levels and coronary heart disease (CHD) risk, but whether this association is causal remains to be ascertained. A Mendelian randomization approach was employed to test whether serum total bilirubin is causally linked to CHD. The genetic variant rs6742078--well known to specifically modify levels of serum total bilirubin and accounting for up to 20% of the variance in circulating serum total bilirubin levels--was used as an instrumental variable. In pooled analysis of estimates reported from published genome-wide association studies, every copy of the T allele of rs6742078 was associated with 0.42 standard deviation (SD) higher levels of serum total bilirubin (95% confidence interval, 0.40 to 0.43). Based on combined data from the Coronary Artery Disease Genome wide Replication and Meta-analyses and the Coronary Artery Disease (C4D) Genetics Consortium involving a total of 36,763 CHD cases and 76,997 controls, the odds ratio for CHD per copy of the T allele was 1.01 (95% confidence interval, 0.99 to 1.04). The odds ratio of CHD for a 1 SD genetically elevated serum total bilirubin level was 1.03 (95% confidence interval, 0.98 to 1.09). The current findings casts doubt on a strong causal association of serum total bilirubin levels with CHD. The inverse associations demonstrated in observational studies may be driven by biases such as unmeasured confounding and/or reverse causation. However, further research in large-scale consortia is needed. Copyright © 2015 Elsevier Inc. All rights reserved.

Diagnostic and prognostic factors for acute encephalopathy.

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Motojima, Yukiko; Nagura, Michiaki; Asano, Yoshitaka; Arakawa, Hiroshi; Takada, Eiko; Sakurai, Yoshio; Moriwaki, Koichi; Tamura, Masanori

2016-11-01

Acute encephalopathy has the possibility of sequelae. While early treatment is required to prevent the development of sequelae, differential diagnosis is of the utmost priority. The aim of this study was therefore to identify parameters that can facilitate early diagnosis and prediction of outcome of acute encephalopathy. We reviewed the medical charts of inpatients from 2005 to 2011 and identified 33 patients with febrile status epilepticus. Subjects were classified into an acute encephalopathy group (n = 20) and a febrile convulsion group (n = 13), and the parameters serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), ammonia (NH 3 ), cerebrospinal fluid (CSF) tau protein, and CSF interleukin-6 compared between them. Furthermore, the relationship between each parameter and prognosis was investigated in the encephalopathy group. Significant differences in serum AST, ALT, and LDH were observed between the febrile convulsion and acute encephalopathy group. Moreover, a significant difference in serum LDH was noted between the patients with and without developmental regression at the time of hospital discharge in the encephalopathy group. In particular, CSF tau protein was found to be highly likely to indicate progress, with CSF tau protein >1000 pg/dL associated with poor prognosis leading to developmental regression. Serum AST, ALT and LDH may be related to early diagnosis and prognosis, and should be carefully investigated in patients with encephalopathy. CSF tau protein could also be used as an indicator of poor prognosis in acute encephalopathy. © 2016 Japan Pediatric Society.

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

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

2017-09-13

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

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

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

2017-06-01

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

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

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

2016-10-01

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

Does aetiology of neonatal encephalopathy and hypoxic-ischaemic encephalopathy influence the outcome of treatment?

Science.gov (United States)

Mcintyre, Sarah; Badawi, Nadia; Blair, Eve; Nelson, Karin B

2015-04-01

Neonatal encephalopathy, a clinical syndrome affecting term-born and late preterm newborn infants, increases the risk of perinatal death and long-term neurological morbidity, especially cerebral palsy. With the advent of therapeutic hypothermia, a treatment designed for hypoxic or ischaemic injury, associated mortality and morbidity rates have decreased. Unfortunately, only about one in eight neonates (95% confidence interval) who meet eligibility criteria for therapeutic cooling apparently benefit from the treatment. Studies of infants in representative populations indicate that neonatal encephalopathy is a potential result of a variety of antecedents and that asphyxial complications at birth account for only a small percentage of neonatal encephalopathy. In contrast, clinical case series suggest that a large proportion of neonatal encephalopathy is hypoxic or ischaemic, and trials of therapeutic hypothermia are specifically designed to include only infants exposed to hypoxia or ischaemia. This review addresses the differences, definitional and methodological, between infants studied and investigations undertaken, in population studies compared with cooling trials. It raises the question if there may be subgroups of infants with a clinical diagnosis of hypoxic-ischaemic encephalopathy (HIE) in whom the pathobiology of neonatal neurological depression is not fundamentally hypoxic or ischaemic and, therefore, for whom cooling may not be beneficial. In addition, it suggests approaches to future trials of cooling plus adjuvant therapy that may contribute to further improvement of care for these vulnerable neonates. © The Authors. Journal compilation © 2015 Mac Keith Press.

Encephalopathy and liver transplantation.

Science.gov (United States)

Chavarria, Laia; Cordoba, Juan

2013-06-01

Liver transplantation (LT) candidates experience frequently episodic or persistent hepatic encephalopathy. In addition, these patients can exhibit neurological comorbidities that contribute to cognitive impairment in the pre-transplant period. Assessment of the respective contribution of hepatic encephalopathy or comorbidities in the cognitive manifestations is critical to estimate the neurological benefits of restoring liver function. Magnetic resonance imaging and spectroscopy are useful to assess the impact of liver failure or comorbidities. This assessment is critical to decide liver transplant in difficult cases. In the early postoperative period, LT is commonly complicated by a confusional syndrome. The possible role of persisting hepatic encephalopathy in its development has not been clearly established. The origin is usually considered multifactorial and relates to complications following LT, such as infections, rejection, primary liver dysfunction, immunosuppressors, etc.… The diagnosis and treatment is based in the recognition of comorbidities and optimal care of metabolic disturbances. Several studies have demonstrated recovery of cognitive function after LT in patients that have exhibited hepatic encephalopathy. However, some deficits may persist specifically among patients with persistent HE. Other factors present before LT that contribute to a worse neuropsychological outcome after LT are diabetes mellitus and alcohol consumption. Long-term after LT, cognitive function may worsen in relation to vascular risk factors.

Hashimoto's encephalopathy

DEFF Research Database (Denmark)

Montagna, Giacomo; Imperiali, Mauro; Agazzi, Pamela

2016-01-01

Hashimoto's encephalopathy (HE) is a rare not well understood, progressive and relapsing multiform disease, characterized by seizures, movement disorders, subacute cognitive dysfunction, psychiatric symptoms and responsiveness to steroid therapy. The disorder is generally associated with thyroid ...... diseases and the most common feature is the presence of anti-thyroperoxidase antibodies (TPOAb). Patients are usually euthyroid or mildly hypothyroid at presentation. All age groups can be affected. The pathophysiology is still unclear, especially the link between elevated serum TPOAb...... and the encephalopathy. Most reported cases occurred in women and girls. Unspecific symptoms, non-pathognomonic laboratory neurophysiology and neuroimaging features make its diagnosis a real challenge for clinicians.The case of a 16 year old boy, with a clinical picture of HE associated with hypothyroidism...

Magnetic polymer-silica composites as bioluminescent sensors for bilirubin detection

Energy Technology Data Exchange (ETDEWEB)

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

2016-11-01

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

Magnetic polymer-silica composites as bioluminescent sensors for bilirubin detection

International Nuclear Information System (INIS)

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

2016-01-01

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

Association between Helicobacter pylori seropositivity and Hepatic Encephalopathy

International Nuclear Information System (INIS)

Behroozian, R.; Faramarzpur, M.; Rahimi, E.

2010-01-01

Objective: The knowledge on Helicobacter pylori (H. pylori) contribution in the pathology of the liver and biliary tract diseases in human is very limited. The aim of this study was to assess the probable association between H. pylori seropositivity and hepatic encephalopathy. Methodology: This is a case control study conducted through three groups, cirrhotics with hepatic encephalopathy (HE), cirrhotics without HE and healthy controls. All subjects were examined serologically for determination of IgG class antibodies to H. pylori based on ELISA technique. Results: H. pylori seropositivity was present in 88% cirrhotic patients with hepatic encephalopathy, 86% cirrhotics without hepatic encephalopathy and 66% healthy controls. Conclusion: According to our results, H. pylori seropositivity rate in cirrhotic patients with or without hepatic encephalopathy was higher than healthy controls. But H. pylori seropositivity rate was not significantly different among cirrhotics with hepatic encephalopathy and those without it.

Hepatic Encephalopathy

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Full Text Available ... Get Worse? How is HE Diagnosed? Prior to Treatment Who treats HE? Preparing for your Medical Appointment Hepatic Encephalopathy Treatment Options Treatment Basics Treatment Medications Importance of Adhering ...

Memantine, a noncompetitive NMDA receptor antagonist improves hyperammonemia-induced encephalopathy and acute hepatic encephalopathy in rats

NARCIS (Netherlands)

Vogels, B. A.; Maas, M. A.; Daalhuisen, J.; Quack, G.; Chamuleau, R. A.

1997-01-01

The aim of this study was to investigate the possible role of N-methyl-D-aspartate (NMDA)-receptor overactivity in two different experimental rat models of encephalopathy: subacute encephalopathy caused by severe hyperammonemia in portacaval-shunted rats (AI-PCS rats) and acute hepatic

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

International Nuclear Information System (INIS)

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

1983-01-01

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

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

Science.gov (United States)

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

2017-08-01

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

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

Science.gov (United States)

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

2016-11-01

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

Metronidazole-induced encephalopathy in a patient with liver cirrhosis.

Science.gov (United States)

Cheong, Hyeong Cheol; Jeong, Taek Geun; Cho, Young Bum; Yang, Bong Joon; Kim, Tae Hyeon; Kim, Haak Cheoul; Cho, Eun-Young

2011-06-01

Encephalopathy is a disorder characterized by altered brain function, which can be attributed to various causes. Encephalopathy associated with metronidazole administration occurs rarely and depends on the cumulative metronidazole dose, and most patients with this condition recover rapidly after discontinuation of therapy. Because metronidazole is metabolized in the liver and can be transported by the cerebrospinal fluid and cross the blood-brain barrier, it may induce encephalopathy even at a low cumulative dose in patients with hepatic dysfunction. We experienced a patient who showed ataxic gait and dysarthric speech after receiving metronidazole for the treatment of hepatic encephalopathy that was not controlled by the administration of lactulose. The patient was diagnosed as metronidazole-induced encephalopathy, and stopping drug administration resulted in a complete recovery from encephalopathy. This case shows that caution should be exercised when administering metronidazole because even a low dose can induce encephalopathy in patients with liver cirrhosis.

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

Science.gov (United States)

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

2017-02-01

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

The clinical outcome and neuroimaging of acute encephalopathy after status epilepticus in Dravet syndrome.

Science.gov (United States)

Tian, Xiaojuan; Ye, Jintang; Zeng, Qi; Zhang, Jing; Yang, Xiaoling; Liu, Aijie; Yang, Zhixian; Liu, Xiaoyan; Wu, Xiru; Zhang, Yuehua

2018-06-01

To analyze the clinical outcome and neuroimaging over a long duration follow-up in the currently largest series of acute encephalopathy after status epilepticus in patients with Dravet syndrome. Clinical and neuroimaging data of patients with Dravet syndrome with a history of acute encephalopathy (coma >24h) after status epilepticus from February 2005 to December 2016 at Peking University First Hospital were reviewed retrospectively. Thirty-five patients (15 males, 20 females) with a history of acute encephalopathy were enrolled from a total of 624 patients with Dravet syndrome (5.6%). The median onset age of acute encephalopathy was 3 years 1 month. The duration of status epilepticus varied between 40 minutes to 12 hours. Thirty-four patients had a high fever when status epilepticus occurred, and only one had a normal temperature. Coma lasted from 2 to 20 days. Twelve patients died and 23 survived with massive neurological regression. The median follow-up time was 2 years 1 month. Neuroimaging of 20 out of 23 survivors during the recovery phase showed diverse degrees of cortical atrophy with or without subcortical lesions. Acute encephalopathy after status epilepticus is more prone to occur in patients with Dravet syndrome who had a high fever. The mortality rate is high in severe cases. Survivors are left with severe neurological sequelae but often with either no seizure or low seizure frequency. Acute encephalopathy is more prone to occur in patients with Dravet syndrome with a high fever. The mortality rate is high for acute encephalopathy after status epilepticus in patients with Dravet syndrome. Survivors have neurological sequelae. © 2018 The Authors. Developmental Medicine & Child Neurology published by John Wiley & Sons Ltd on behalf of Mac Keith Press.

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

International Nuclear Information System (INIS)

Mohan, Hari; Gopinathan, C.

1988-02-01

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

Autism spectrum disorder and epileptic encephalopathy: common causes, many questions.

Science.gov (United States)

Srivastava, Siddharth; Sahin, Mustafa

2017-01-01

Epileptic encephalopathies represent a particularly severe form of epilepsy, associated with cognitive and behavioral deficits, including impaired social-communication and restricted, repetitive behaviors that are the hallmarks of autism spectrum disorder (ASD). With the advent of next-generation sequencing, the genetic landscape of epileptic encephalopathies is growing and demonstrates overlap with genes separately implicated in ASD. However, many questions remain about this connection, including whether epileptiform activity itself contributes to the development of ASD symptomatology. In this review, we compiled a database of genes associated with both epileptic encephalopathy and ASD, limiting our purview to Mendelian disorders not including inborn errors of metabolism, and we focused on the connection between ASD and epileptic encephalopathy rather than epilepsy broadly. Our review has four goals: to (1) discuss the overlapping presentations of ASD and monogenic epileptic encephalopathies; (2) examine the impact of the epilepsy itself on neurocognitive features, including ASD, in monogenic epileptic encephalopathies; (3) outline many of the genetic causes responsible for both ASD and epileptic encephalopathy; (4) provide an illustrative example of a final common pathway that may be implicated in both ASD and epileptic encephalopathy. We demonstrate that autistic features are a common association with monogenic epileptic encephalopathies. Certain epileptic encephalopathy syndromes, like infantile spasms, are especially linked to the development of ASD. The connection between seizures themselves and neurobehavioral deficits in these monogenic encephalopathies remains open to debate. Finally, advances in genetics have revealed many genes that overlap in ties to both ASD and epileptic encephalopathy and that play a role in diverse central nervous system processes. Increased attention to the autistic features of monogenic epileptic encephalopathies is warranted for

Hepatic encephalopathy. Imaging Findings

International Nuclear Information System (INIS)

Carrillo, Maria Claudia; Bermudez Munoz, Sonia; J Morillo, Anibal

2007-01-01

Hepatic encephalopathy occurs in patients with chronic hepatic insufficiency and can produce abnormalities in the central nervous system, which can be observed in MRI studies. Traditionally, these imaging findings include symmetrical hyper intensities in T1-weighted sequences in the basal ganglia (mainly globus pallidus), involving also the substantia nigra, mesencephalic tegmentum, frontal and occipital cortex. These areas appear of normal intensity in T2-weighted imaging sequences. Other entities that can lead to similar findings include manganese intoxication and type-1 neurofibromatosis. Currently, with the advent of MR spectroscopy, abnormalities in patients with clinical and subclinical hepatic encephalopathy have been described. After hepatic transplantation, hyper intensities of the basal ganglia and the MR spectroscopic findings may disappear within 3 months to 1 year, suggesting a functional, more than a structural damage. This article will demonstrate the MR findings of patients with hepatic encephalopathy due to chronic hepatic insufficiency.

Hepatic Encephalopathy

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Full Text Available ... to continue to work to my full capacity? Will I be able to drive? Patient Stories Angie M. Caregiver for Brother Charles DiAngelo Hepatic Encephalopathy Jason Dedmon Alcohol-related Cirrhosis ...

Hepatic Encephalopathy

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Full Text Available ... responsible for the daily needs of another person. Caregivers can be a friend, spouse, life partner, parent, sibling or other family member. What is HE? Hepatic Encephalopathy, sometimes referred to as ...

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

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Didem Cemile Yesilirmak

2015-11-01

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

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

Science.gov (United States)

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

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

Science.gov (United States)

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

2009-02-01

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

Management of hyperbilirubinemia in near ... term newborns according to American Academy of Pediatrics Guidelines: Report of three cases

OpenAIRE

Naomi Esthemita Dewanto; Rinawati Rohsiswatmo

2009-01-01

All neonates have a transient rise in bilirubin levels, and about 30-50% of infants become visibly jaundiced.1,2 Most jaundice is benign; however, because of the potential brain toxicity of bilirubin, newborn infants must be monitored to identify those who might develop severe hyperbilirubinemia and, in rare cases, acute bilirubin encephalopathy or kernicterus. Ten percent of term infants and 25% of near-term infants have significant hyperbilirubinemia and requir...

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

Science.gov (United States)

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

2016-02-01

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

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

Science.gov (United States)

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

2015-09-18

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

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

Science.gov (United States)

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

2015-01-01

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

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

Science.gov (United States)

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

2016-05-01

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

Hashimoto's encephalopathy: Report of three cases

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Jan-Shun Chang

2014-11-01

Full Text Available Both severe thyrotoxicosis and hypothyroidism may affect brain function and cause a change in consciousness, as seen with a thyroid storm or myxedema coma. However, encephalopathy may also develop in patients with autoimmune thyroid diseases independent of actual thyroid function level, and this is known as Hashimoto's encephalopathy. Although most patients are found to have Hashimoto's thyroiditis, less frequently they have Graves' disease. Clinical manifestations include epilepsy, disturbance of consciousness, cognitive impairment, memory loss, myoclonus, hallucinations, stroke-like episodes, tremor, involuntary movements, language impairment, and gait impairment. Hashimoto's encephalopathy is a relatively rare disease. As a good response can be obtained with corticosteroid therapy, early diagnosis and treatment is very beneficial for patients. Here we report three patients with Hashimoto's encephalopathy with typical manifestations of hallucinations that were associated with hypothyroidism, hyperthyroidism, and euthyroid status, respectively. They all showed a dramatic response to methylprednisolone pulse therapy.

Wernicke encephalopathy in a patient with liver failure

Science.gov (United States)

Zhao, Pan; Zhao, Yanling; Wei, Zhenman; Chen, Jing; Yan, Lilong

2016-01-01

Abstract Early recognition and diagnosis of Wernicke encephalopathy is pivotal for the prognosis of this medical emergency, especially in patients with liver failure which predisposes individuals to develop hepatic encephalopathy. For these patients, distinguishing between hepatic encephalopathy and Wernicke encephalopathy is a challenge in real-world clinical practice. A male patient with 21-year medical history of liver cirrhosis presented diarrhea and ascites. One month before this visit, he was noted to have poor appetite and progressive fatigue. After admission, although several major symptoms, including diarrhea, ascites, hyponatremia, and hypoproteinemia, were greatly improved through appropriate treatments, his laboratory indicators were not changed much. His appetite was not reversed at discharge. On the 5th day after discharge, the patient suddenly became reluctant to speak and did not remember the recent happenings. Simultaneously, unsteady gait and strabismus occurred. On the basis of clinical manifestations and brain magnetic resonance imaging scan results, the patient was diagnosed as Wernicke encephalopathy and these relative symptoms were resolved after intravenous vitamin B1. To our knowledge, this is the second case report of Wernicke encephalopathy developing in a critically ill cirrhotic patient without hepatocellular carcinoma or operative intervention. Wernicke encephalopathy may be underdiagnosed in these patients and this case raises physicians’ awareness of its possible onset. PMID:27399058

Minimal hepatic encephalopathy in patients with cirrhosis by measuring liver stiffness and hepatic venous pressure gradient.

Science.gov (United States)

Sharma, Praveen; Kumar, Ashish

2012-01-01

Transient elastography (TE) of liver and hepatic venous pressure gradient (HVPG) allows accurate prediction of cirrhosis and its complications in patients with chronic liver disease. There is no study on prediction of minimal hepatic encephalopathy (MHE) using TE and HVPG in patients with cirrhosis. Consecutive cirrhotic patients who never had an episode of hepatic encephalopathy (HE) were enrolled. All patients were assessed by psychometry (number connection test (NCT-A and B), digit symbol test (DST), serial dot test (SDT), line tracing test (LTT)), critical flicker frequency test (CFF), TE by FibroScan and HVPG. MHE was diagnosed if there were two or more abnormal psychometry tests (± 2 SD controls). 150 patients with cirrhosis who underwent HVPG were screened; 91 patients (61%, age 44.0 ± 11.4 years, M:F:75:16, Child's A:B:C 18:54:19) met the inclusion criteria. Fifty three (58%) patients had MHE (Child A (7/18, 39%), Child B (32/54, 59%) and Child C (14/19, 74%)). There was no significant difference between alanine aminotranferease (ALT), aspartate aminotransferase (AST) and total bilirubin level in patients with MHE versus non MHE. Patients with MHE had significantly lower CFF than non MHE patients (38.4 ± 3.0 vs. 40.2 ± 2.2 Hz, P = 0.002). TE and HVPG in patients with MHE did not significantly differ from patients with no MHE (30.9 ± 17.2 vs. 29.8 ± 18.2 KPas, P = 0.78; and 13.6 ± 2.7 vs. 13.6 ± 3.2 mmHg, P = 0.90, respectively).There was significant correlation of TE with Child's score (0.25, P = 0.01), MELD (0.40, P = 0.001) and HVPG (0.72, P = 0.001) while no correlation with psychometric tests, CFF and MHE. TE by FibroScan and HVPG cannot predict minimal hepatic encephalopathy in patients with cirrhosis.

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

DEFF Research Database (Denmark)

Sato, H; Honoré, B; Brodersen, R

1988-01-01

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

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

Science.gov (United States)

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

2013-09-27

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

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

Directory of Open Access Journals (Sweden)

Jyoti Bala

2015-01-01

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

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

International Nuclear Information System (INIS)

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

1986-01-01

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

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

Science.gov (United States)

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

2017-01-01

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

Computerized tomography in acute toxic encephalopathy

International Nuclear Information System (INIS)

Aoki, Nobuhiko; Kaneshi, Kunio; Mizuguchi, Masashi; Kurihara, Eiji.

1983-01-01

We experienced three cases of acute toxic encephalopathy, including a case of probable Reye syndrome, which had similar and unique CT findings in their acute stage; symmetrical low density area in the thalamus and the dentate nucleus, followed by changes in cerebellar hemispheres and around lateral ventricles. The CT findings, common to probable Reye syndrome and other acute toxic encephalopathy, may suggest the possibility of similar pathogenesis of brain damage in both disorders. The authors propose that present cases are a new subgroup in acute toxic encephalopathy, because of their similar and unique CT features. (author)

Hepatic Encephalopathy

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Full Text Available ... to Treatment Who treats HE? Preparing for your Medical Appointment Hepatic Encephalopathy Treatment Options Treatment Basics Treatment ... treatment. Being a fully-informed participant in your medical care is an important factor in staying as ...

Hepatic Encephalopathy

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Full Text Available ... your body when your liver isn’t working well, it may affect your brain and cause HE. ... it apparent that the liver is not doing well. These could be the symptoms of Hepatic Encephalopathy ( ...

Hepatic Encephalopathy

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Full Text Available ... build-up and painful swelling of the legs (edema) and abdomen (ascites) or hepatic encephalopathy. For more ... build up and painful swelling of the legs (edema) and abdomen (ascites) Bruising and bleeding easily Enlarged ...

Hepatic Encephalopathy

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Full Text Available ... People ALF Near You Events ALF Blogs Financial Information Policies Advocacy Patient Advisory Council Media Center Careers ... and abdomen (ascites) or hepatic encephalopathy. For more information about cirrhosis of the liver and symptoms, call ...

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Full Text Available ... Hemochromatosis Hepatic Encephalopathy Hepatitis A Hepatitis B Hepatitis C Intrahepatic Cholestasis of Pregnancy (ICP) Jaundice In Newborns ... are the common causes of cirrhosis? Hepatitis B & C Alcohol-related Liver Disease Non-alcoholic Fatty Liver ...

Plasma malondialdehyde, bilirubin, homocysteine and total ...

African Journals Online (AJOL)

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

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

Science.gov (United States)

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

2017-06-01

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

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Full Text Available ... friend, spouse, life partner, parent, sibling or other family member. What is HE? Hepatic Encephalopathy, sometimes referred ... disease is. It’s important for you and your family to become familiar with the signs of Hepatic ...

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Full Text Available ... important for you and your family to become familiar with the signs of Hepatic Encephalopathy so you ... team evaluates the person’s overall physical and mental health, plan to pay for transplant related medical expenses, ...

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Full Text Available ... become familiar with the signs of Hepatic Encephalopathy so you can tell your doctor right away if ... with continuous treatment, HE can usually be controlled. So it’s important to tell your doctor about any ...

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Full Text Available ... Hepatic Encephalopathy so you can tell your doctor right away if you think you may have it. ... Site Map © COPYRIGHT 2017 AMERICAN LIVER FOUNDATION. ALL RIGHTS RESERVED. Your Liver Overview

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Full Text Available ... Hepatic Encephalopathy Treatment Options Treatment Basics Treatment Medications Importance of Adhering to Your Treatment Plan Long-Term Considerations Patient Support Finding Support Services Peer Support Groups Financial Assistance Support for My Loved Ones Resources Find ...

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

Science.gov (United States)

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

2017-04-28

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

Qualifying and quantifying minimal hepatic encephalopathy

DEFF Research Database (Denmark)

Morgan, Marsha Y; Amodio, Piero; Cook, Nicola A

2016-01-01

Minimal hepatic encephalopathy is the term applied to the neuropsychiatric status of patients with cirrhosis who are unimpaired on clinical examination but show alterations in neuropsychological tests exploring psychomotor speed/executive function and/or in neurophysiological variables. There is ......Minimal hepatic encephalopathy is the term applied to the neuropsychiatric status of patients with cirrhosis who are unimpaired on clinical examination but show alterations in neuropsychological tests exploring psychomotor speed/executive function and/or in neurophysiological variables...... analytical techniques may provide better diagnostic information while the advent of portable wireless headsets may facilitate more widespread use. A large number of other diagnostic tools have been validated for the diagnosis of minimal hepatic encephalopathy including Critical Flicker Frequency......, the Inhibitory Control Test, the Stroop test, the Scan package and the Continuous Reaction Time; each has its pros and cons; strengths and weaknesses; protagonists and detractors. Recent AASLD/EASL Practice Guidelines suggest that the diagnosis of minimal hepatic encephalopathy should be based on the PHES test...

Chronic traumatic encephalopathy: The unknown disease.

Science.gov (United States)

Martínez-Pérez, R; Paredes, I; Munarriz, P M; Paredes, B; Alén, J F

2017-04-01

Chronic traumatic encephalopathy is a neurodegenerative disease produced by accumulated minor traumatic brain injuries; no definitive premortem diagnosis and no treatments are available for chronic traumatic encephalopathy. Risk factors associated with chronic traumatic encephalopathy include playing contact sports, presence of the apolipoprotein E4, and old age. Although it shares certain histopathological findings with Alzheimer disease, chronic traumatic encephalopathy has a more specific presentation (hyperphosphorylated tau protein deposited as neurofibrillary tangles, associated with neuropil threads and sometimes with beta-amyloid plaques). Its clinical presentation is insidious; patients show mild cognitive and emotional symptoms before progressing to parkinsonian motor signs and finally dementia. Results from new experimental diagnostic tools are promising, but these tools are not yet available. The mainstay of managing this disease is prevention and early detection of its first symptoms. Copyright © 2014 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

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

Science.gov (United States)

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

2016-01-01

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

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Full Text Available ... 1 (von Gierke) Hemochromatosis Hepatic Encephalopathy Hepatitis A Hepatitis B Hepatitis C Intrahepatic Cholestasis of Pregnancy (ICP) Jaundice ... diseases. What are the common causes of cirrhosis? Hepatitis B & C Alcohol-related Liver Disease Non-alcoholic Fatty ...

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

Directory of Open Access Journals (Sweden)

Ahmad Shah Farhat

2016-12-01

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

MRI finding of ethylmalonic encephalopathy: case report

International Nuclear Information System (INIS)

Kim, Jin Yong; Lee, Shi Kyung; Han, Chun Hwan; Rho, Eun Jin

2002-01-01

Ethylmalonic encephalopathy is a rare syndrom characterized by developmental delay, acrocyanosis, petechiae, chronic diarrhea, and ethylmalonic, lactic, and methylsuccinic aciduria. We report the MRI finding of ethylmalonic encephalopathy including previously unreported intracranial hematoma

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

International Nuclear Information System (INIS)

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

2017-01-01

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

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

Science.gov (United States)

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

2017-08-01

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

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

Science.gov (United States)

Thakkar, Pareshkumar; Chavda, Hardas; Doshi, Vikas

2017-05-15

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

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

Science.gov (United States)

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

1991-06-01

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

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

Science.gov (United States)

De Luca, Daniele; Dell'Orto, Valentina

2017-09-01

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

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

LENUS (Irish Health Repository)

Cotter, Aoife G

2013-05-16

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

Follow-up of extreme neonatal hyperbilirubinaemia in 5- to 10-year-old children

DEFF Research Database (Denmark)

Vandborg, Pernille Kure; Hansen, Bo Mølholm; Greisen, Gorm

2015-01-01

AIM: To investigate whether infants with neonatal hyperbilirubinaemia but without intermediate or advanced bilirubin encephalopathy develop long-term sequelae, with impairment of motor development, executive function, or hearing. METHOD: This nested double-cohort study included 167 exposed children...... (107 males, 60 females) born in Denmark 2000 to 2005 at gestational age ≥35 weeks with a total serum bilirubin ≥450 μmol/L (26.3mg/dL) and 163 age-, sex-, and gestational age-matched unexposed children (103 males, 60 females). The children were examined at a mean age of 7.7 years (SD 1.7y) using...... spectrum disorder recorded in national registries. INTERPRETATION: No evidence was found of an increased risk of deficits in motor development, executive function, or hearing in children with extreme hyperbilirubinaemia who did not have intermediate or advanced bilirubin encephalopathy....

Evaluation of BiliCare™ transcutaneous bilirubin device in Japanese newborns.

Science.gov (United States)

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

2017-10-01

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

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

Science.gov (United States)

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

2016-09-01

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

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

Science.gov (United States)

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

2014-01-01

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

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

Science.gov (United States)

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

2017-01-24

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

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

NARCIS (Netherlands)

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

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

Posterior encephalopathy with vasospasm: MRI and angiography

International Nuclear Information System (INIS)

Weidauer, S.; Gaa, J.; Lanfermann, H.; Zanella, F.E.; Sitzer, M.; Hefner, R.

2003-01-01

Posterior encephalopathy is characterised by headache, impairment of consciousness, seizures and progressive visual loss. MRI shows bilateral, predominantly posterior, cortical and subcortical lesions with a distribution. Our aim was to analyse the MRI lesion pattern and angiographic findings because the pathophysiology of posterior encephalopathy is incompletely understood. We report three patients with clinical and imaging findings consistent with posterior encephalopathy who underwent serial MRI including diffusion-weighted imaging (DWI) and construction of apparent diffusion coefficient (ADC) maps, and four-vessel digital subtraction angiography (DSA). DWI revealed symmetrical subcortical and cortical parieto-occipital high signal. High and also low ADCs indicated probable vasogenic and cytotoxic oedema. On follow-up there was focal cortical laminar necrosis, while the white-matter lesions resolved almost completely, except in the arterial border zones. DSA revealed diffuse arterial narrowing, slightly more marked in the posterior circulation. These findings suggest that posterior encephalopathy may in some cases be due to diffuse, severe vasospasm affecting especially in the parieto-occipital grey matter, with its higher vulnerability to ischemia. Cerebral vasospasm due to digitoxin intoxication, resulting in posterior encephalopathy, has not yet been described previously. (orig.)

Bilirubin in Urine: MedlinePlus Lab Test Information

Science.gov (United States)

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

Portal hemodynamics in chronic portal-systemic encephalopathy

International Nuclear Information System (INIS)

Takashi, Motohide; Igarashi, Masahiko; Hino, Shinichi; Takayasu, Kenichi; Goto, Nobuaki; Musha, Hirotaka; Ohnishi, Kunihiko; Okuda, Kunio

1985-01-01

A portal hemodynamic study was made in 7 consecutive patients with chronic portal-systemic encephalopathy by percutaneous transhepatic catheterization of the portal vein and injecting contrast medium into the superior mesenteric vein or by superior mesenteric arterial portography in comparison with patients without encephalopathy studied by percutaneous catheterization of these veins. It is suggested that chronic portal-systemic encephalopathy is a result of a large collateral route shunting a large proportion of the superior mesenteric venous blood into systemic circulation, and that development of such collaterals precludes formation of large esophageal varices. (Auth.)

No oxygen delivery limitation in hepatic encephalopathy

DEFF Research Database (Denmark)

Gjedde, Albert; Keiding, Susanne; Vilstrup, Hendrik

2010-01-01

to choose between cause and effect in three groups of volunteers, including healthy control subjects (HC), patients with cirrhosis of the liver without hepatic encephalopathy (CL), and patients with cirrhosis with acute hepatic encephalopathy. Compared to HC subjects, blood flow and energy metabolism had......Hepatic encephalopathy is a condition of reduced brain functioning in which both blood flow and brain energy metabolism declined. It is not known whether blood flow or metabolism is the primary limiting factor of brain function in this condition. We used calculations of mitochondrial oxygen tension...

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

Science.gov (United States)

Alla, Suresh K.

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

Monitoring and analysis of bovine spongiform encephalopathy (BSE) testing in Denmark using statistical models

DEFF Research Database (Denmark)

Paisley, Larry

2002-01-01

The evolution of monitoring and surveillance for bovine spongiform encephalopathy (BSE) from the phase of passive surveillance that began in the United Kingdom in 1988 until the present is described. Currently, surveillance for BSE in Europe consists of mass testing of cattle slaughtered for human...

Diffusion MR findings in cyclosporin-A induced encephalopathy

International Nuclear Information System (INIS)

Aydin, Kubilay; Minareci, Ozenc; Donmez, Fuldem; Tuzun, Umit; Atamer, Tanju

2004-01-01

Cyclosporin encephalopathy is a well-known entity, which is clinically characterized by altered mental status, vision problems, focal neurological deficits and seizures. The exact pathophysiology of the cyclosporin encephalopathy has not yet been defined. We report the diffusion-weighted MR imaging and proton MR spectroscopy findings in a case of cyclosporin encephalopathy. The white-matter lesions with reversible restricted diffusion supported the hypothesis of reversible vasospasm induced by the cyclosporin. (orig.)

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

Science.gov (United States)

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

2014-01-01

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

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

Science.gov (United States)

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

2016-08-03

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

Birth defects in children with newborn encephalopathy

NARCIS (Netherlands)

Felix, JF; Badawi, N; Kurinczuk, JJ; Bower, C; Keogh, JM; Pemberton, PJ

2000-01-01

This study was designed to investigate birth defects found in association with newborn encephalopathy. All possible birth defects were ascertained in a population-based study of 276 term infants with moderate or severe encephalopathy and 564 unmatched term control infants. A strong association

Role of central nervous system in acute radiation syndrome functional metabolic encephalopathy

International Nuclear Information System (INIS)

Court, L.; Fatome, M.; Gueneau, J.; Rouif, G.; Pasquier, C.; Bassant, M.H.; Dufour, R.

In adult rabbit, the effect on the brain of a whole-body or encephalic gamma irradiation is a function of the absorbed dose and begins after 25 rads. Three phases are described in the mechanism of radiation effect. In the initial phase, irradiation acts as a direct stimulus of cerebral structures. The second phase is a response towards aggression which includes: the effect of stimulation of various cerebral structures; their response and the induced feed-back mechanism; the release of metabolites inducing a functional metabolic encephalopathy in which occur: modification of blood pressure; modification of pulmonary ventilation; modification of acido-basic blood equilibrium. The third phase consists of functional recovery [fr

Frequency of helicobacter pylori antibodies in porto-systemic encephalopathy,

International Nuclear Information System (INIS)

Sethar, G.H.; Ahmed, R.; Afsar, S.; Zuberi, B.F.

2004-01-01

Objective: To study the frequency of Helicobacter pylori antibodies in patients presenting with porto-systemic encephalopathy due to liver disease. Patients and Methods: During the study period, seventy-six patients of porto-systemic encephalopathy due to liver diseases was selected. These subjects were evaluated for hepatic encephalopathy grade, modified Child-Pugh classification and were managed according to the standard practices. These patients were evaluated for Helicobacter (H. pylori) antibody status by ELlSA (Abbott Laboratories) method. Results: Out of 76 patients studied and tested for H. pylori antibodies, 48(63.2%) were males and 28(36.8%) were females with age ranging between 17 and 85 years. Out of 76 patients who presented with porto-systemic encephalopathy, 59(77.6%) had a positive H. pylori antibody test. Thirty-five of these were males and 24 were females. A significant number of patients who presented with higher grade of encephalopathy were H. pylori antibody positive (p<0.001). Conclusion: In this study, frequency of H. pylori antibodies was significantly high in patients of porto-systematic encephalopathy. (author)

Acute hyperammonemic encephalopathy with features on diffusion-weighted images: Report of two cases

International Nuclear Information System (INIS)

Kim, Ja Young; Yu, In Kyu

2015-01-01

Acute hyperammonemic encephalopathy is a rare toxic encephalopathy caused by accumulated plasma ammonia. A few literatures are reported about MRI findings of acute hyperammonemic encephalopathy. It is different from the well-known chronic hepatic encephalopathy. The clinical symptom and MRI findings of acute hyperammonemic encephalopathy can be reversible with proper treatment. Acute hepatic encephalopathy involves the cingulate cortex, diffuse cerebral cortices, insula, bilateral thalami on diffusion-weighted imaging (DWI), and fluid-attenuated inversion-recovery. Acute hepatic encephalopathy might mimic hypoxic-ischemic encephalopathy because of their similar predominant involving sites. We experienced 2 cases of acute hyperammonemic encephalopathy consecutively. They showed restricted diffusion at the cingulate cortex, cerebral cortices, insula, and bilateral dorsomedial thalami on DWI. One patient underwent acute fulminant hepatitis A, the other patient with underlying chronic liver disease had acute liver failure due to hepatotoxicity of tuberculosis medication. In this report, we presented the characteristic features of DWI in acute hyperammonemic encephalopathy. In addition, we reviewed articles on MRI findings of acute hyperammonemic encephalopathy.

Acute hyperammonemic encephalopathy with features on diffusion-weighted images: Report of two cases

Energy Technology Data Exchange (ETDEWEB)

Kim, Ja Young; Yu, In Kyu [Dept. of Radiology, Eulji University Hospital, Daejeon (Korea, Republic of)

2015-02-15

Acute hyperammonemic encephalopathy is a rare toxic encephalopathy caused by accumulated plasma ammonia. A few literatures are reported about MRI findings of acute hyperammonemic encephalopathy. It is different from the well-known chronic hepatic encephalopathy. The clinical symptom and MRI findings of acute hyperammonemic encephalopathy can be reversible with proper treatment. Acute hepatic encephalopathy involves the cingulate cortex, diffuse cerebral cortices, insula, bilateral thalami on diffusion-weighted imaging (DWI), and fluid-attenuated inversion-recovery. Acute hepatic encephalopathy might mimic hypoxic-ischemic encephalopathy because of their similar predominant involving sites. We experienced 2 cases of acute hyperammonemic encephalopathy consecutively. They showed restricted diffusion at the cingulate cortex, cerebral cortices, insula, and bilateral dorsomedial thalami on DWI. One patient underwent acute fulminant hepatitis A, the other patient with underlying chronic liver disease had acute liver failure due to hepatotoxicity of tuberculosis medication. In this report, we presented the characteristic features of DWI in acute hyperammonemic encephalopathy. In addition, we reviewed articles on MRI findings of acute hyperammonemic encephalopathy.

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

Science.gov (United States)

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

2013-01-01

Microporous anodic aluminum oxide (AAO) membranes were modified by 3-glycidoxypropyltrimethoxysilane to produce terminal epoxy groups. These were used to covalently link hydroxyethyl celluloses (HEC) to amplify reactive groups of AAO membrane. The hydroxyl groups of HEC-AAO composite membrane were further modified with 1,4-butanediol diglycidyl ether to link arginine as an affinity ligand. The contents of HEC and arginine of arginine-immobilized HEC-AAO membrane were 52.1 and 19.7mg/g membrane, respectively. As biomedical adsorbents, the arginine-immobilized HEC-AAO membranes were tested for bilirubin removal. The non-specific bilirubin adsorption on the unmodified HEC-AAO composite membranes was 0.8mg/g membrane. Higher bilirubin adsorption values, up to 52.6mg/g membrane, were obtained with the arginine-immobilized HEC-AAO membranes. Elution of bilirubin showed desorption ratio was up to 85% using 0.3M NaSCN solution as the desorption agent. Comparisons equilibrium and dynamic capacities showed that dynamic capacities were lower than the equilibrium capacities. In addition, the adsorption mechanism of bilirubin and the effects of temperature, initial concentration of bilirubin, albumin concentration and ionic strength on adsorption were also investigated. Copyright © 2012 Elsevier B.V. All rights reserved.

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

International Nuclear Information System (INIS)

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

1982-01-01

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

Electroencephalography and Brain MRI Patterns in Encephalopathy.

Science.gov (United States)

Wabulya, Angela; Lesser, Ronald P; Llinas, Rafael; Kaplan, Peter W

2016-04-01

Using electroencephalography (EEG) and histology in patients with diffuse encephalopathy, Gloor et al reported that paroxysmal synchronous discharges (PSDs) on EEG required combined cortical gray (CG) and "subcortical" gray (SCG) matter pathology, while polymorphic delta activity (PDA) occurred in patients with white matter pathology. In patients with encephalopathy, we compared EEG findings and magnetic resonance imaging (MRI) to determine if MRI reflected similar pathological EEG correlations. Retrospective case control study of 52 cases with EEG evidence of encephalopathy and 50 controls without evidence of encephalopathy. Review of clinical, EEG and MRI data acquired within 4 days of each other. The most common EEG finding in encephalopathy was background slowing, in 96.1%. We found PSDs in 0% of cases with the combination of CG and SCG abnormalities. Although 13.5% (n=7) had PSDs on EEG; 3 of these had CG and 4 had SCG abnormalities. A total of 73.1% (38/52) had white matter abnormalities-of these 28.9% (11/38) had PDA. PSDs were found with either CG or "SCG" MRI abnormalities and did not require a combination of the two. In agreement with Gloor et al, PDA occurred with white matter MRI abnormalities in the absence of gray matter abnormalities. © EEG and Clinical Neuroscience Society (ECNS) 2015.

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

Science.gov (United States)

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

2013-04-01

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

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

Science.gov (United States)

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

2015-01-01

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

STXBP1 encephalopathy

DEFF Research Database (Denmark)

Stamberger, Hannah; Nikanorova, Marina; Willemsen, Marjolein H

2016-01-01

OBJECTIVE: To give a comprehensive overview of the phenotypic and genetic spectrum of STXBP1 encephalopathy (STXBP1-E) by systematically reviewing newly diagnosed and previously reported patients. METHODS: We recruited newly diagnosed patients with STXBP1 mutations through an international networ......, and the degree of ID. Accordingly, we hypothesize that seizure severity and ID present 2 independent dimensions of the STXBP1-E phenotype. STXBP1-E may be conceptualized as a complex neurodevelopmental disorder rather than a primary epileptic encephalopathy....

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

Science.gov (United States)

Orlov, Sergey; Goncharova, Iryna; Urbanová, Marie

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

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

Science.gov (United States)

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

2017-01-26

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

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

NARCIS (Netherlands)

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

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

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

NARCIS (Netherlands)

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

2011-01-01

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

Malnutrition-induced Wernicke's encephalopathy following a water-only fasting diet.

Science.gov (United States)

Hutcheon, Deborah A

2015-02-01

Wernicke's encephalopathy is a critical condition of neurological dysfunction resulting from a deficiency in thiamine. Chronic alcoholism is recognized as the most common cause of Wernicke's encephalopathy, but other causes, including fasting/starvation and malnutrition, have been documented within the scientific literature. These causes may not be readily recognized by healthcare professionals and may lead to Wernicke's encephalopathy being overlooked as a diagnosis when a nonalcoholic patient presents with classic signs and symptoms of the disorder. A narrative review of thiamine and its relationship to the development, diagnosis, and treatment of Wernicke's encephalopathy is presented based on a review of evidence-based guidelines and published research. To heighten awareness of the development of Wernicke's encephalopathy in fasted/starved and malnourished patients and to contribute to the scientific body of knowledge for the identification and management of Wernicke's encephalopathy in these patients, the clinical course and treatment of an adult woman who developed Wernicke's encephalopathy following a 40-day water-only fasting diet is outlined. Clinical suspicion was required to identify the patient's condition and initiate immediate intervention through parenteral thiamine administration. Oral thiamine supplementation of 100 to 800 mg per day for 6 months was required to aid recovery. The patient's clinical course and response to treatment illustrate the necessity for clinical awareness and suspicion of Wernicke's encephalopathy among healthcare professionals, timely and adequate parenteral thiamine administration, and oral thiamine supplementation at therapeutic doses to correct the nutrient deficiency, halt the progression of Wernicke's encephalopathy, and promote recovery. © 2014 American Society for Parenteral and Enteral Nutrition.

Radiographical findings in patients with liver cirrhosis and hepatic encephalopathy.

Science.gov (United States)

Elwir, Saleh; Hal, Hassan; Veith, Joshua; Schreibman, Ian; Kadry, Zakiyah; Riley, Thomas

2016-08-01

Hepatic encephalopathy is a common complication encountered in patients with liver cirrhosis. Hepatic encephalopathy is not reflected in the current liver transplant allocation system. Correlation was sought between hepatic encephalopathy with findings detected on radiographic imaging studies and the patient's clinical profile. A retrospective analysis was conducted of patients with cirrhosis, who presented for liver transplant evaluation in 2009 and 2010. Patients with hepatocellular carcinoma, ejection fraction less than 60% and who had a TIPS (transjugular intrahepatic portosystemic shunting) procedure or who did not complete the evaluation were excluded. Statistical analysis was performed and variables found to be significant on univariate analysis (P encephalopathy group (n = 58) and a control group (n = 59). Univariate analysis found that a smaller portal vein diameter, smaller liver antero-posterior diameter, liver nodularity and use of diuretics or centrally acting medications showed significant correlation with hepatic encephalopathy. This association was confirmed for smaller portal vein, use of diuretics and centrally acting medications in the multivariate analysis. A decrease in portal vein diameter was associated with increased risk of encephalopathy. Identifying patients with smaller portal vein diameter may warrant screening for encephalopathy by more advanced psychometric testing, and more aggressive control of constipation and other factors that may precipitate encephalopathy. © The Author(s) 2015. Published by Oxford University Press and the Digestive Science Publishing Co. Limited.

Brain Magnetic Resonance Imaging and Magnetic Resonance Spectroscopy Findings of Children with Kernicterus

International Nuclear Information System (INIS)

Sarı, Sahabettin; Yavuz, Alpaslan; Batur, Aabdussamet; Bora, Aydın; Caksen, Huseyin

2015-01-01

The term kernicterus, or bilirubin encephalopathy, is used to describe pathological bilirubin staining of the basal ganglia, brain stem, and cerebellum, and is associated with hyperbilirubinemia. Kernicterus generally occurs in untreated hyperbilirubinemia or cases where treatment is delayed. Magnetic resonance imaging (MRI)-based studies have shown characteristic findings in kernicterus. The objective of our study was to describe the role of 1 H magnetic resonance spectroscopy (MRS) in demonstrating these metabolic changes and to review conventional MRI findings of kernicterus. Forty-eight pediatric cases with kernicterus were included in this study. MRI and MRS examinations were performed on variable dates (10–29 days after birth). NAA, Cr, Cho, NAA/Cr, NAA/Cho, and Cho/Cr values were evaluated visually and by computer analysis. There was no statistically significant difference between the NAA and Cho levels in the acute kernicterus patients and the control group (healthy patients), whereas both were significantly elevated in the chronic kernicterus patients. Both the mean NAA/Cr and Cho/Cr ratio values were significantly higher in the acute and chronic cases compared to the control group. The NAA/Cho ratio value was statistically lower in the acute cases than in the control group while it was similar in the chronic cases. Conventional MR imaging and 1 H-MRS are important complementary tools in the diagnostics of neonatal bilirubin encephalopathy. This study provided important information for applying these MR modalities in the evaluation of neonates with bilirubin encephalopathy

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

Science.gov (United States)

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

2017-07-01

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

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

Science.gov (United States)

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

2018-06-01

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

Bovine Spongiform Encephalopathy (BSE), or Mad Cow Disease

Science.gov (United States)

... the CDC Bovine Spongiform Encephalopathy (BSE), or Mad Cow Disease Note: Javascript is disabled or is not ... spongiform encephalopathy) is a progressive neurological disorder of cattle that results from infection by an unusual transmissible ...

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

Science.gov (United States)

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

2016-01-01

Bilirubin has shown cutaneous wound healing potential in some preliminary studies. Here we hypothesize that bilirubin facilitates wound healing in diabetic rats by modulating important healing factors/candidates and antioxidant parameters in a time-dependent manner. Diabetes was induced in male Wistar rats by streptozotocin. In all diabetic rats wounds were created under pentobarbitone anesthesia. All the rats were divided into two groups, of which one (control) was treated with ointment base and other with bilirubin ointment (0.3%). Wound closer measurement and tissue collection were done on days 3, 7, 14 and 19 post-wounding. The relative expressions of hypoxia inducible factor-1 alpha (HIF-1α), vascular endothelial growth factor (VEGF), stromal cell-derived factor-1 alpha (SDF-1α), transforming growth factor- beta1 (TGF-β1()), tumor necrosis factor-α (TNF-α) and interlukin-10 (IL-10) mRNA and proteins and the mRNA of interlukin-1 beta (IL-1β) and matrix metalloprteinase-9 (MMP-9) were determined in the wound tissues. CD-31 staining and collagen content were evaluated by immunohistochemistry and picrosirius red staining, respectively. Histopathological changes were assessed by H&E staining. The per cent wound closer was significantly higher from day 7 onwards in bilirubin-treated rats. HIF-1α, VEGF, SDF-1α, TGF-β1, IL-10 mRNA and protein levels were significantly higher on days 3, 7 and 14 in bilirubin-treated rats. The mRNA expression and protein level of TNF-α and the mRNA of IL-1β and MMP-9 were progressively and markedly reduced in bilirubin-treated rats. The collagen deposition and formation of blood vessels were greater in bilirubin-treated rats. Bilirubin markedly facilitated cutaneous wound healing in diabetic rats by modulating growth factors, cytokines, neovasculogenesis and collagen contents to the wound site. Topical application of bilirubin ointment might be of great use in cutaneous wound healing in diabetic patients. Copyright © 2015

Hypertensive encephalopathy in a patient with neonatal thyrotoxicosis

NARCIS (Netherlands)

Pijnenburg, MWH; Zweens, MJ; Bink, MTE; Odink, RJ

1999-01-01

Neonatal hyperthyroidism may give rise to serious cardiovascular complications. A girl with severe thyrotoxicosis in whom hypertensive encephalopathy developed is described. Conclusion Neonatal thyrotoxicosis can give rise to hypertension and may lead to hypertensive encephalopathy.

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

Science.gov (United States)

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

2016-06-01

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

Hepatic Encephalopathy

Medline Plus

Full Text Available ... of brain function in people with advanced liver disease. When your liver is damaged it can no longer remove toxic substances from your blood. These toxins build up and can travel through your body until they reach your brain, causing mental and physical symptoms of HE. Hepatic Encephalopathy often ...

Molecular & Genetic Investigation of Tau in Chronic Traumatic Encephalopathy

Science.gov (United States)

2015-10-01

AWARD NUMBER: W81XWH-14-1-0399 TITLE: Molecular & Genetic Investigation of Tau in Chronic Traumatic Encephalopathy PRINCIPAL INVESTIGATOR: John F...Include area code) October 2015 Annual Report 30 Sep 2014 - 29 Sep 2015 Molecular & Genetic Investigation of Tau in Chronic Traumatic Encephalopathy John... encephalopathy (CTE), but the underlying molecular changes remain unclear. Here, biochemical and genetic studies that deepen our understanding of the

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

Science.gov (United States)

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

2015-11-15

Bilirubin is thought to exert anti-inflammatory effects by inhibiting vascular cell adhesion molecule-1 (VCAM-1)-dependent leukocyte migration and by suppressing the expression of inducible nitric oxide synthase (iNOS). As VCAM-1 and iNOS are important mediators of tissue injury in the dextran sodium sulfate (DSS) murine model of inflammatory colitis, we examined whether bilirubin prevents colonic injury in DSS-treated mice. Male C57BL/6 mice were administered 2.5% DSS in the drinking water for 7 days, while simultaneously receiving intraperitoneal injections of bilirubin (30 mg/kg) or potassium phosphate vehicle. Disease activity was monitored, peripheral blood counts and serum nitrate levels were determined, and intestinal specimens were analyzed for histological injury, leukocyte infiltration, and iNOS expression. The effect of bilirubin on IL-5 production by HSB-2 cells and on Jurkat cell transendothelial migration also was determined. DSS-treated mice that simultaneously received bilirubin lost less body weight, had lower serum nitrate levels, and exhibited reduced disease severity than vehicle-treated animals. Concordantly, histopathological analyses revealed that bilirubin-treated mice manifested significantly less colonic injury, including reduced infiltration of eosinophils, lymphocytes, and monocytes, and diminished iNOS expression. Bilirubin administration also was associated with decreased eosinophil and monocyte infiltration into the small intestine, with a corresponding increase in peripheral blood eosinophilia. Bilirubin prevented Jurkat migration but did not alter IL-5 production. In conclusion, bilirubin prevents DSS-induced colitis by inhibiting the migration of leukocytes across the vascular endothelium and by suppressing iNOS expression. Copyright © 2015 the American Physiological Society.

Evaluation and Management of Hepatic Encephalopathy: Current Status and Future Directions

OpenAIRE

Suraweera, Duminda; Sundaram, Vinay; Saab, Sammy

2016-01-01

Hepatic encephalopathy is a spectrum of neurocognitive manifestations often seen in patients with liver injury or rarely in patients with portosystemic shunting without liver injury. It can be divided into minimal (covert) hepatic encephalopathy and overt hepatic encephalopathy, depending on the severity. Patients with hepatic encephalopathy have compromised clinical outcomes, decreased quality of life, and increased healthcare utilization, often resulting in a heavy financial and personal bu...

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

Science.gov (United States)

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

2018-04-01

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

Wernicke's encephalopathy as a complication of gastroparesis after ...

African Journals Online (AJOL)

Wernicke's encephalopathy is a common complication of malnutrition, alcohol abuse and gastric outlet obstruction. We describe a patient who developed Wernicke's encephalopathy secondary to gastroparesis, with no significant evidence of malnutrition, alcohol abuse, or gastric outlet obstruction.

Genetics Home Reference: STXBP1 encephalopathy with epilepsy

Science.gov (United States)

... Resources (8 links) Boston Children's Hospital: Epilepsy and Seizure Disorder in Children Centers for Disease Control and Prevention: ... stxbp1 encephalopathy with epilepsy Merck Manual Consumer Version: Seizure Disorders Orphanet: Early infantile epileptic encephalopathy Patient Support and ...

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

Science.gov (United States)

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

2017-03-31

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

Reversible dementia with psychosis: Hashimoto's encephalopathy.

Science.gov (United States)

Mocellin, Ramon; Lubman, Dan I; Lloyd, John; Tomlinson, E Bruce; Velakoulis, Dennis

2006-12-01

A case of presumed Hashimoto's encephalopathy (HE) is presented. The presentation included memory loss, delusions, functional decline and culminated in a generalized seizure. Anti-thyroid antibodies were detected and symptoms resolved with prednisolone. Patients with HE may present with prominent neuropsychiatric symptoms, attract psychiatric diagnoses and present to psychiatric services. Primarily a diagnosis of exclusion, HE should be considered in cases of encephalopathy in which standard investigations are negative.

Post-partum posterior reversible encephalopathy syndrome

OpenAIRE

B. V. Triveni; Salman Mohammed Sheikh; Deepak Shedde

2014-01-01

Posterior Reversible Encephalopathy Syndrome (PRES) is a clinicopathological syndrome associated with various clinical conditions presenting with headache, encephalopathy, seizure and cortical visual disturbances. Radiological findings in PRES are thought to be due to vasogenic edema predominantly in posterior cerebral hemispheres and are reversible with appropriate management. We present a case of post partum PRES,A 29 year old primigravida of 33 weeks 3 days period of gestation who prese...

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

Science.gov (United States)

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

1995-08-01

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

Cell damage by bilirubin and light

International Nuclear Information System (INIS)

Granli, T.

1993-01-01

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

[Follow-up of newborns with hypoxic-ischaemic encephalopathy].

Science.gov (United States)

Martínez-Biarge, M; Blanco, D; García-Alix, A; Salas, S

2014-07-01

Hypothermia treatment for newborn infants with hypoxic-ischemic encephalopathy reduces the number of neonates who die or have permanent neurological deficits. Although this therapy is now standard of care, neonatal hypoxic-ischaemic encephalopathy still has a significant impact on the child's neurodevelopment and quality of life. Infants with hypoxic-ischaemic encephalopathy should be enrolled in multidisciplinary follow-up programs in order to detect impairments, to initiate early intervention, and to provide counselling and support for families. This article describes the main neurodevelopmental outcomes after term neonatal hypoxic-ischaemic encephalopathy. We offer recommendations for follow-up based on the infant's clinical condition and other prognostic indicators, mainly neonatal neuroimaging. Other aspects, such as palliative care and medico-legal issues, are also briefly discussed. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

Wernicke’s encephalopathy following hyperemesis gravidarum

Directory of Open Access Journals (Sweden)

Leila Pourali

2016-06-01

Full Text Available Background: ″Wernicke’s Korsakoff″ syndrome is the most important complication of severe thiamine deficiency. The term refers to two different syndromes, each representing a different stage of the disease. Wernicke’s encephalopathy (WE is an acute syndrome requiring emergent treatment to prevent death and neurologic morbidity. Korsakoff syndrome (KS refers to a chronic neurologic condition that usually occurs as a consequence of WE. It is a rare complication of hyperemesis gravidarum that confusion, ocular signs, and gait ataxia are the most prevalent symptoms, respectively. Typical brain lesions of wernicke’s encephalopathy (WE are observed at autopsy in 0.4 to 2.8 percent of the general population in the western world and the majority of affected patients are alcoholic. The prevalence of wernicke’s encephalopathy lesions seen on autopsy was 12.5% of alcohol abusers in one report. Among those who with alcohol-related death, it has been reported to be even higher, 29 to 59%. The aim of this study was to report a case of wernicke’s encephalopathy following hyperemesis gravidarum. Case Presentation: A 28-year-old-pregnant woman in 19th weeks of gestation referred to the hospital with hyperemesis, gait ataxia, and dysarthria before that she had hyperemesis gravidarum with weight loss and unresponsive to outpatient and inpatient medical therapy. MRI showed hyperdense lesion around thalamus which was characteristic of wernicke’s encephalopathy. Rapid improvement in patient’s condition occurred after high dose thiamine infusion. Conclusion: In hyperemesis gravidarum, presence of either symptoms of ocular or mental disorder or ataxia must be considered to rule out and appropriate treatment of Wernicke’s syndrome which can cause maternal and fetal death.

The Frequency and Severity of Magnetic Resonance Imaging Abnormalities in Infants with Mild Neonatal Encephalopathy.

Science.gov (United States)

Walsh, Brian H; Neil, Jeffrey; Morey, JoAnn; Yang, Edward; Silvera, Michelle V; Inder, Terrie E; Ortinau, Cynthia

2017-08-01

To assess and contrast the incidence and severity of abnormalities on cerebral magnetic resonance imaging (MRI) between infants with mild, moderate, and severe neonatal encephalopathy who received therapeutic hypothermia. This retrospective cohort studied infants with mild, moderate, and severe neonatal encephalopathy who received therapeutic hypothermia at a single tertiary neonatal intensive care unit between 2013 and 2015. Two neuroradiologists masked to the clinical condition evaluated brain MRIs for cerebral injury after therapeutic hypothermia using the Barkovich classification system. Additional abnormalities not included in this classification system were also noted. The rate, pattern, and severity of abnormalities/injury were compared across the grades of neonatal encephalopathy. Eighty-nine infants received therapeutic hypothermia and met study criteria, 48 with mild neonatal encephalopathy, 35 with moderate neonatal encephalopathy, and 6 with severe neonatal encephalopathy. Forty-eight infants (54%) had an abnormality on MRI. There was no difference in the rate of overall MRI abnormalities by grade of neonatal encephalopathy (mild neonatal encephalopathy 54%, moderate neonatal encephalopathy 54%, and severe neonatal encephalopathy 50%; P= .89). Basal ganglia/thalamic injury was more common in those with severe neonatal encephalopathy (mild neonatal encephalopathy 4%, moderate neonatal encephalopathy 9%, severe neonatal encephalopathy 34%; P = .03). In contrast, watershed injury did not differ between neonatal encephalopathy grades (mild neonatal encephalopathy 36%, moderate neonatal encephalopathy 32%, severe neonatal encephalopathy 50%; P = .3). Mild neonatal encephalopathy is commonly associated with MRI abnormalities after therapeutic hypothermia. The grade of neonatal encephalopathy during the first hours of life may not discriminate adequately between infants with and without cerebral injury noted on MRI after therapeutic hypothermia

Hemolytic Uremic Syndrome-associated Encephalopathy Successfully Treated with Corticosteroids.

Science.gov (United States)

Hosaka, Takashi; Nakamagoe, Kiyotaka; Tamaoka, Akira

2017-11-01

The encephalopathy that occurs in association with hemolytic uremic syndrome (HUS), which is caused by enterohemorrhagic Escherichia coli (E. coli), has a high mortality rate and patients sometimes present sequelae. We herein describe the case of a 20-year-old woman who developed encephalopathy during the convalescent stage of HUS caused by E.coli O26. Hyperintense lesions were detected in the pons, basal ganglia, and cortex on diffusion-weighted brain MRI. From the onset of HUS encephalopathy, we treated the patient with methylprednisolone (mPSL) pulse therapy alone. Her condition improved, and she did not present sequelae. Our study shows that corticosteroids appear to be effective for the treatment of some patients with HUS encephalopathy.

CT diagnosis of hypoxic ischemic encephalopathy

International Nuclear Information System (INIS)

Zhao Xiang; Ma Jiwei; Wu Lide

2004-01-01

Objective: To explore CT characteristics of hypoxic ischemic encephalopathy (HIE), and to improve the accuracy of CT diagnosis. Methods: 50 cases of neonatal asphyxia in perinatal period diagnosed as hypoxic ischemic encephalopathy by CT was analyzed. Results: The main manifestation of hypoxic ischemic encephalopathy is cerebral edema and intracranial hemorrhage. Focal or diffuse hypo-dense lesion and hyper-dense area in various location and morphology were seen on CT images. (1) Localized diffuse hypo-dense area in 1 or 2 cerebral lobe were found in 17 cases, and the lesions were localized in frontal lobe (n=6), in frontotemporal lobe (n=5), and in temporo-occipital lobe (n=6). (2) Hypo-density region involving more than three cerebral lobes were found in 18 cases, and abnormalities were found in frontotemporal and parietal lobe (n=8), accompanying with subarachnoid hemorrhage (n=2); in frontal, temporal and occipital lobe (n=6), in which cerebral hemorrhage was complicated (n=1); and in other cerebral lobe (n=4). (3) Diffuse low-density region in all cerebral lobe were found in 15 cases, in which subarachnoid hemorrhage was complicated in 4 cases, and ventricular hemorrhage was found in 2 case. Conclusion: CT imaging plays an important role in diagnosis of hypoxic ischemic encephalopathy and has shown its clinical value

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

Directory of Open Access Journals (Sweden)

Min Du

2016-12-01

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

LGI1 antibody encephalopathy overlapping with sporadic Creutzfeldt-Jakob disease

Science.gov (United States)

Kim, Boaz; Yoo, Patrick; Sutherland, Tom; Boyd, Alison; Stehmann, Christiane; McLean, Catriona

2016-01-01

Objective: To report a rare case of leucine-rich, glioma inactivated 1 (LGI1) antibody–mediated autoimmune encephalopathy clinically overlapping with pathologically confirmed sporadic Creutzfeldt-Jakob disease (CJD). Methods: The patient was investigated with repeated brain MRI, EEG, CSF examination, whole-body fluorodeoxy-glucose positron emission tomography, genetic analysis of the prion protein gene (PRNP), and extensive serologic screening for paraneoplastic and autoimmune encephalopathy markers. Written informed consent was obtained from the patient's next of kin for access to clinical files for research purposes and for publication. Results: The patient was a 77-year-old man who presented with faciobrachial dystonic seizures (FBDS) secondary to LGI1 antibody–mediated autoimmune encephalopathy, with suggestive MRI findings and a complete response to treatment with combinatorial immunosuppression. Stereotactic biopsy of a nonenhancing T1 hyperintense basal ganglia lesion during the initial FBDS phase, albeit following immunosuppression, did not disclose evidence of lymphocytic inflammation. Following full remission of the FBDS, the patient manifested a rapidly progressive dementia associated with gross motor decline confirmed to be CJD at autopsy (molecular subtype VV3), with no evidence of a pathogenic PRNP mutation. Conclusions: Our patient highlights that these rare diseases are not invariably mutually exclusive and underscores the benefits of comprehensive neuropathologic examination of the brain to achieve an accurate diagnosis, especially in complex cases when the clinical trajectory dramatically deviates and a concomitant disease may need to be conscientiously considered to best explain the new clinical course. PMID:27354985

Evaluation and Management of Hepatic Encephalopathy: Current Status and Future Directions

Science.gov (United States)

Suraweera, Duminda; Sundaram, Vinay; Saab, Sammy

2016-01-01

Hepatic encephalopathy is a spectrum of neurocognitive manifestations often seen in patients with liver injury or rarely in patients with portosystemic shunting without liver injury. It can be divided into minimal (covert) hepatic encephalopathy and overt hepatic encephalopathy, depending on the severity. Patients with hepatic encephalopathy have compromised clinical outcomes, decreased quality of life, and increased healthcare utilization, often resulting in a heavy financial and personal burden on caregivers. The diagnosis remains largely clinical, with the exclusion of possible other causes for the altered mental status. Current treatment strategies include nonabsorbable disaccharides and antibiotics. This review will focus on the diagnosis, management and clinical impact of hepatic encephalopathy. PMID:27377741

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

Directory of Open Access Journals (Sweden)

Levitt DG

2014-09-01

Full Text Available David G Levitt,1 Michael D Levitt2 1Department of Integrative Biology and Physiology, University of Minnesota, Minneapolis, MN, USA; 2Research Service, Veterans Affairs Medical Center, Minneapolis, MN, USAAbstract: Serum bilirubin measurements are commonly obtained for the evaluation of ill patients and to screen for liver disease in routine physical exams. An enormous research effort has identified the multiple mechanisms involved in the production and metabolism of conjugated (CB and unconjugated bilirubin (UB. While the qualitative effects of these mechanisms are well understood, their expected quantitative influence on serum bilirubin homeostasis has received less attention. In this review, each of the steps involved in bilirubin production, metabolism, hepatic cell uptake, and excretion is quantitatively examined. We then attempt to predict the expected effect of normal and defective function on serum UB and CB levels in health and disease states including hemolysis, extra- and intrahepatic cholestasis, hepatocellular diseases (eg, cirrhosis, hepatitis, and various congenital defects in bilirubin conjugation and secretion (eg, Gilbert's, Dubin–Johnson, Crigler–Najjar, Rotor syndromes. Novel aspects of this review include: 1 quantitative estimates of the free and total UB and CB in the plasma, hepatocyte, and bile; 2 detailed discussion of the important implications of the recently recognized role of the hepatic OATP transporters in the maintenance of CB homeostasis; 3 discussion of the differences between the standard diazo assay versus chromatographic measurement of CB and UB; 4 pharmacokinetic implications of the extremely high-affinity albumin binding of UB; 5 role of the enterohepatic circulation in physiologic jaundice of newborn and fasting hyperbilirubinemia; and 6 insights concerning the clinical interpretation of bilirubin measurements.Keywords: liver, conjugation, diazo, albumin, Rotor

Can Excess Bilirubin Levels Cause Learning Difficulties?

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

2002-01-01

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

Rare and unusual ... or are they? Less commonly diagnosed encephalopathies associated with systemic disease.

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Weathers, Allison L; Lewis, Steven L

2009-04-01

Encephalopathy due to hepatic or renal failure, electrolyte disturbances, or the administration of benzodiazepines and narcotics is commonly encountered, well reviewed in the literature, and, therefore, not usually missed. This article focuses on encephalopathies that were previously well described but may be overlooked by modern clinicians, as well as those that are still taught in the classroom but seldom thought of in practice. Due to the presumed relative rarity of these cases and emphasis on the well-memorized "classic" clinical presentations, these often treatable, and perhaps not so rare, encephalopathies due to systemic medical illness may go undiagnosed and untreated. Pancreatic encephalopathy, Wernicke's encephalopathy, and pellagra encephalopathy are reviewed in detail; cefepime and ifosfamide encephalopathies are discussed as examples of specific medication-induced encephalopathies. Septic encephalopathy, central pontine myelinolysis, and fat embolism syndrome are briefly reviewed. The encephalopathies reviewed have the potential for devastating neurological consequences if recognition and, therefore, treatment are delayed. Clinical improvement for many of these syndromes depends on prompt intervention. This article highlights some representative examples of less-commonly diagnosed metabolic and toxic encephalopathies.

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

NARCIS (Netherlands)

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

2000-01-01

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

Research progress of BOLD-fMRI in minimal hepatic encephalopathy

International Nuclear Information System (INIS)

Zhou Zhiming; Zhao Jiannong

2013-01-01

The minimal hepatic encephalopathy is the early stage of hepatic encephalopathy. It has few apparent clinical symptoms and specific manifestations, and is difficult to diagnose. In the recent years, BOLD-fMRI has been used to study hepatic encephalopathy gradually. Through detection of the brain neuron activities in different states, it can not only locate the abnormal activity of brain functional areas, but also can find the changes of brain functional connectivity. BOLD- fMRI combining with other MR technologies can explore the pathology and pathogenesis of minimal hepatic encephalopathy from micro to macro and from structure to function. (authors)

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

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

2016-06-01

Captive waterbuck ( Kobus ellipsiprymnus ) that appear clinically healthy have been noted to have high serum bilirubin concentrations compared with other ruminants; however, questions remain about the physiologic factors affecting bilirubin concentration and its potential association with underlying disease and icteric serum or mucous membranes. Serum bilirubin concentrations of healthy and diseased waterbuck housed at the San Diego Zoo Safari Park from 1989 to 2012 were retrospectively analyzed to determine any link between icteric serum, total bilirubin concentration (tBili), and disease entities in this species. Total bilirubin and direct (dBili) bilirubin concentrations and the prevalence of icteric serum were compared by subspecies, age group, and health status; associations with complete blood count and biochemical results and clinical diagnosis were assessed. No significant differences were found in tBili or dBili between Ellipsen (n = 32) and Defassa (n = 29) subspecies or in juveniles (n = 22) versus adults (n = 39). Clinically healthy waterbuck (n = 40) had significantly higher tBili (mean ± 2SD, 7.9 ± 1.2 mg/dl; P bilirubin (2.2-6.2 mg/dl). These results suggest healthy waterbuck have relatively high tBili and dBili compared with related species. Icteric serum may be seen in up to 15% of healthy animals in the absence of icteric tissues.

Potentially modifiable factors contributing to sepsis-associated encephalopathy.

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Sonneville, Romain; de Montmollin, Etienne; Poujade, Julien; Garrouste-Orgeas, Maïté; Souweine, Bertrand; Darmon, Michael; Mariotte, Eric; Argaud, Laurent; Barbier, François; Goldgran-Toledano, Dany; Marcotte, Guillaume; Dumenil, Anne-Sylvie; Jamali, Samir; Lacave, Guillaume; Ruckly, Stéphane; Mourvillier, Bruno; Timsit, Jean-François

2017-08-01

Identifying modifiable factors for sepsis-associated encephalopathy may help improve patient care and outcomes. We conducted a retrospective analysis of a prospective multicenter database. Sepsis-associated encephalopathy (SAE) was defined by a score on the Glasgow coma scale (GCS) sepsis at ICU admission, of whom 1341 (53%) had sepsis-associated encephalopathy. After adjusting for baseline characteristics, site of infection, and type of admission, the following factors remained independently associated with sepsis-associated encephalopathy: acute renal failure [adjusted odds ratio (aOR) = 1.41, 95% confidence interval (CI) 1.19-1.67], hypoglycemia 10 mmol/l (aOR = 1.37, 95% CI 1.09-1.72), hypercapnia >45 mmHg (aOR = 1.91, 95% CI 1.53-2.38), hypernatremia >145 mmol/l (aOR = 2.30, 95% CI 1.48-3.57), and S. aureus (aOR = 1.54, 95% CI 1.05-2.25). Sepsis-associated encephalopathy was associated with higher mortality, higher use of ICU resources, and longer hospital stay. After adjusting for age, comorbidities, year of admission, and non-neurological SOFA score, even mild alteration of mental status (i.e., a score on the GCS of 13-14) remained independently associated with mortality (adjusted hazard ratio = 1.38, 95% CI 1.09-1.76). Acute renal failure and common metabolic disturbances represent potentially modifiable factors contributing to sepsis-associated encephalopathy. However, a true causal relationship has yet to be demonstrated. Our study confirms the prognostic significance of mild alteration of mental status in patients with sepsis.

Dengue viral infections as a cause of encephalopathy

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Malavige G

2007-01-01

Full Text Available The aim of this study was to determine the clinical characteristics and poor prognostic factors associated with high mortality in dengue encephalopathy. Fifteen patients with confirmed dengue infections, who developed encephalopathy, were recruited from two tertiary care hospitals in Colombo, Sri Lanka. Among the factors that contributed to encephalopathy were: Acute liver failure (73%, electrolyte imbalances (80% and shock (40%. Five (33.3% patients developed seizures. Disseminated intravascular coagulation was seen in five (33.3%. Secondary bacterial infections were observed in 8 (53.3% of our patients. The overall mortality rate was 47%.

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

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Gianfranco Cervellin

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

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

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

2018-02-01

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

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

International Nuclear Information System (INIS)

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

1981-01-01

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

Bilirubin: an endogenous molecule with antiviral activity in vitro.

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Rosaria eSantangelo

2012-03-01

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

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

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

2017-09-01

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

Minimal hepatic encephalopathy characterized by parallel use of the continuous reaction time and portosystemic encephalopathy tests

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Lauridsen, M M; Schaffalitzky de Muckadell, O B; Vilstrup, H

2015-01-01

Minimal hepatic encephalopathy (MHE) is a frequent complication to liver cirrhosis that causes poor quality of life, a great burden to caregivers, and can be treated. For diagnosis and grading the international guidelines recommend the use of psychometric tests of different modalities (computer...... based vs. paper and pencil). To compare results of the Continuous Reaction time (CRT) and the Portosystemic Encephalopathy (PSE) tests in a large unselected cohort of cirrhosis patients without clinically detectable brain impairment and to clinically characterize the patients according to their test...

The research of melatonin in hypoxic-ischemic encephalopathy

International Nuclear Information System (INIS)

Sun Bin; Feng Xing; Qian Zhihong; Shi Ming

2006-01-01

Objective: To elucidate the function of melatonin in the pathogenesis and the prognosis of hypoxic-ischemic encephalopathy (HIE) and provide the pathophysiology basis for therapying HIE with melatonin. Methods: The level of plasma melatonin of twenty normal term infants and twenty modest HIE and twenty middle-severity HIE in their acute phase and recovery phase were assayed respectively with radioimmunoassay (RIA). Then compare the difference of the melatonin level among these neonates. Results: (1) For modest HIE, the melatonin level was higher than that in the normal in the acute phase and there was no difference to the normal in the recovery phase. (2) There was no difference between the melatonin level in middle-severity HIE in the acute phase and that in the normal, but in the recovery phase it was higher than that in the normal. (3) For modest HIE, the melatonin level in acute phase was higher than that in the recovery phase, but for middle-severity HIE, it was adverse. (4) In the acute phase, the level in modest HIE was higher than that in the middle-severity HIE, but on the contrary in the recovery phase. Conclusion: Melatonin have protection action on HIE. The prognosis of modest HIE neonates with rising melatonin level in the acute phase is better than that with lower melatonin level of middle-severity HIE. (authors)

Normalization of the psychometric hepatic encephalopathy score for ...

African Journals Online (AJOL)

Aim: To construct normal values for the tests of the psychometric hepatic encephalopathy score (PHES) and evaluate the prevalence of minimal hepatic encephalopathy (MHE) among Turkish patients with liver cirrhosis. Materials and Methods: One hundred and eighty-five healthy subjects and sixty patients with liver ...

Topiramate increases the risk of valproic acid-induced encephalopathy.

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Noh, Young; Kim, Dong Wook; Chu, Kon; Lee, Soon-Tae; Jung, Keun-Hwa; Moon, Hye-Jin; Lee, Sang Kun

2013-01-01

Metabolic encephalopathy is a rare but serious complication of valproic acid (VPA) therapy that usually presents with impaired consciousness or increased seizure frequency. Although it has been suggested that topiramate (TPM) increases the risk of VPA-induced encephalopathy, the additional risk in patients receiving TPM therapy has not been evaluated. We reviewed all adult patients who took VPA between January 2005 and February 2009 at the Seoul National University Hospital and identified patients with VPA-induced encephalopathy based on clinical and electroencephalography (EEG) data. Information on sex, age, serum ammonia level, serum VPA level, liver function test, and EEG was collected from patient registry and medical data. We enrolled 8,372 patients who received VPA therapy and 1,236 patients who received VPA/TPM combination therapy. We identified 11 patients with VPA-induced encephalopathy (0.13%), 7 of whom received a combination therapy of VPA and TPM. The odds ratio of VPA-induced encephalopathy with TPM over that without TPM was 10.16. There were no significant differences in sex distribution, number of antiepileptic agents, ammonia level, VPA serum level, underlying diseases, dosage of VPA, duration of VPA treatment, treatment of encephalopathy, and outcomes between the two groups. Our study showed that the prevalence of VPA-induced encephalopathy is approximately 0.1% among patients treated with VPA and that the risk of this condition, although still low, can increase by approximately 10 times in the presence of TPM therapy. Based on these results, we suggest that TPM should be carefully used in patients receiving VPA treatment. Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.

Hepatic encephalopathy in acute-on-chronic liver failure.

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Lee, Guan-Huei

2015-10-01

The presence of hepatic encephalopathy (HE) within 4 weeks is part of the criteria for defining acute-on-chronic liver failure (ACLF). The pathophysiology of HE is complex, and hyperammonemia and cerebral hemodynamic dysfunction appear to be central in the pathogenesis of encephalopathy. Recent data also suggest that inflammatory mediators may have a significant role in modulating the cerebral effect of ammonia. Multiple prospective and retrospective studies have shown that hepatic encephalopathy in ACLF patients is associated with higher mortality, especially in those with grade III-IV encephalopathy, similar to that of acute liver failure (ALF). Although significant cerebral edema detected by CT in ACLF patients appeared to be less common, specialized MRI imaging was able to detect cerebral edema even in low grade HE. Ammonia-focused therapy constitutes the basis of current therapy, as in the treatment of ALF. Emerging treatment strategies focusing on modulating the gut-liver-circulation-brain axis are discussed.

Clinical manifestations and treatment response of steroid in pediatric Hashimoto encephalopathy.

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Yu, Hee Joon; Lee, Jeehun; Seo, Dae Won; Lee, Munhyang

2014-07-01

Hashimoto encephalopathy is a steroid-responsive encephalopathy associated with elevated titers of antithyroid antibodies. Clinical symptoms are characterized by behavioral and cognitive changes, speech disturbance, seizures, myoclonus, psychosis, hallucination, involuntary movements, cerebellar signs, and coma. The standard treatment is the use of corticosteroids along with the treatment of any concurrent dysthyroidism. Other options are immunoglobulins and plasmapheresis. We described symptoms and outcomes on 3 teenage girls with Hashimoto encephalopathy. Presenting symptoms were seizure or altered mental status. One patient took levothyroxine due to hypothyroidism before presentation of Hashimoto encephalopathy. After confirmation of elevated antithyroid antibodies, all patients were treated with steroids. One patient needed plasmapheresis because of the lack of response to steroids and immunoglobulins. Hashimoto encephalopathy should be considered in any patient presenting with acute or subacute unexplained encephalopathy and seizures. Even though the use of steroids is the first line of treatment, plasmapheresis can rescue steroid-resistant patients. © The Author(s) 2013.

Wernicke encephalopathy in children and adolescents.

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Lallas, Matt; Desai, Jay

2014-11-01

Wernicke encephalopathy is caused by thiamine (vitamin B1) deficiency. It is generally considered to be a disease of adult alcoholics. However, it is known to occur in the pediatric population and in non-alcoholic conditions. We searched PubMed with the key words Wernicke, thiamine, pediatric, children and adolescents and selected publications that were deemed appropriate. The global prevalence rates of hunger, poverty and resultant nutrient deprivation have decreased in the 21st century. However, several scenarios which may predispose to Wernicke encephalopathy may be increasingly prevalent in children and adolescents such as malignancies, intensive care unit stays and surgical procedures for the treatment of obesity. Other predisposing conditions include magnesium deficiency and defects in the SLC19A3 gene causing thiamine transporter-2 deficiency. The classic triad consists of encephalopathy, oculomotor dysfunction and gait ataxia but is not seen in a majority of patients. Treatment should be instituted immediately when the diagnosis is suspected clinically without waiting for laboratory confirmation. Common magnetic resonance findings include symmetric T2 hyperintensities in dorsal medial thalamus, mammillary bodies, periaqueductal gray matter, and tectal plate. Wernicke encephalopathy is a medical emergency. Delay in its recognition and treatment may lead to significant morbidity, irreversible neurological damage or even death. This article aims to raise the awareness of this condition among pediatricians.

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

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Gorchynski, Julie

2009-05-01

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

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

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

2009-05-01

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

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

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Rubin, Rosalyn A.; And Others

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

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

International Nuclear Information System (INIS)

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

1977-01-01

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

Genetics Home Reference: familial encephalopathy with neuroserpin inclusion bodies

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... Home Health Conditions FENIB Familial encephalopathy with neuroserpin inclusion bodies Printable PDF Open All Close All Enable ... expand/collapse boxes. Description Familial encephalopathy with neuroserpin inclusion bodies ( FENIB ) is a disorder that causes progressive ...

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

International Nuclear Information System (INIS)

Mohan, Hari; Gopinathan, C.

1989-01-01

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

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

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

2017-11-01

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

Cannabidiol improves brain and liver function in a fulminant hepatic failure-induced model of hepatic encephalopathy in mice.

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Avraham, Y; Grigoriadis, Nc; Poutahidis, T; Vorobiev, L; Magen, I; Ilan, Y; Mechoulam, R; Berry, Em

2011-04-01

Hepatic encephalopathy is a neuropsychiatric disorder of complex pathogenesis caused by acute or chronic liver failure. We investigated the effects of cannabidiol, a non-psychoactive constituent of Cannabis sativa with anti-inflammatory properties that activates the 5-hydroxytryptamine receptor 5-HT(1A) , on brain and liver functions in a model of hepatic encephalopathy associated with fulminant hepatic failure induced in mice by thioacetamide. Female Sabra mice were injected with either saline or thioacetamide and were treated with either vehicle or cannabidiol. Neurological and motor functions were evaluated 2 and 3 days, respectively, after induction of hepatic failure, after which brains and livers were removed for histopathological analysis and blood was drawn for analysis of plasma liver enzymes. In a separate group of animals, cognitive function was tested after 8 days and brain 5-HT levels were measured 12 days after induction of hepatic failure. Neurological and cognitive functions were severely impaired in thioacetamide-treated mice and were restored by cannabidiol. Similarly, decreased motor activity in thioacetamide-treated mice was partially restored by cannabidiol. Increased plasma levels of ammonia, bilirubin and liver enzymes, as well as enhanced 5-HT levels in thioacetamide-treated mice were normalized following cannabidiol administration. Likewise, astrogliosis in the brains of thioacetamide-treated mice was moderated after cannabidiol treatment. Cannabidiol restores liver function, normalizes 5-HT levels and improves brain pathology in accordance with normalization of brain function. Therefore, the effects of cannabidiol may result from a combination of its actions in the liver and brain. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

MRI and CT appearances in metabolic encephalopathies due to systemic diseases in adults

International Nuclear Information System (INIS)

Bathla, G.; Hegde, A.N.

2013-01-01

The term encephalopathy refers to a clinical scenario of diffuse brain dysfunction, commonly due to a systemic, metabolic, or toxic derangement. Often the clinical evaluation is unsatisfactory in this scenario and imaging plays an important role in the diagnosis, assessment of treatment response, and prognostication of the disorder. Hence, it is important for radiologists to be familiar with the imaging features of some relatively frequently acquired metabolic encephalopathies encountered in the hospital setting. This study reviews the computed tomography (CT) and magnetic resonance imaging (MRI) features of a number of metabolic encephalopathies that occur as part of systemic diseases in adults. The following conditions are covered in this review: hypoglycaemic encephalopathy, hypoxic ischaemic encephalopathy, non-ketotic hyperglycaemia, hepatic encephalopathy, uraemic encephalopathy, hyperammonaemic encephalopathy, and posterior reversible encephalopathy syndrome. MRI is the imaging method of choice in evaluating these conditions. Due to their high metabolic activity, bilateral basal ganglia changes are evident in the majority of cases. Concurrent imaging abnormalities in other parts of the central nervous system often provide useful diagnostic information about the likely underlying cause of the encephalopathy. Besides this, abnormal signal intensity and diffusion restriction patterns on MRI and MR spectroscopy features may provide important clues as to the diagnosis and guide further management. Frequently, the diagnosis is not straightforward and typical imaging features require correlation with clinical and laboratory data for accurate assessment

The Spectrum of Disease in Chronic Traumatic Encephalopathy

Science.gov (United States)

McKee, Ann C.; Stein, Thor D.; Nowinski, Christopher J.; Stern, Robert A.; Daneshvar, Daniel H.; Alvarez, Victor E.; Lee, Hyo-Soon; Hall, Garth; Wojtowicz, Sydney M.; Baugh, Christine M.; Riley, David O.; Kubilus, Caroline A.; Cormier, Kerry A.; Jacobs, Matthew A.; Martin, Brett R.; Abraham, Carmela R.; Ikezu, Tsuneya; Reichard, Robert Ross; Wolozin, Benjamin L.; Budson, Andrew E.; Goldstein, Lee E.; Kowall, Neil W.; Cantu, Robert C.

2013-01-01

Chronic traumatic encephalopathy is a progressive tauopathy that occurs as a consequence of repetitive mild traumatic brain injury. We analysed post-mortem brains obtained from a cohort of 85 subjects with histories of repetitive mild traumatic brain injury and found evidence of chronic traumatic encephalopathy in 68 subjects: all males, ranging…

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

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

2016-01-01

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

Recent advances in hepatic encephalopathy [version 1; referees: 4 approved

Directory of Open Access Journals (Sweden)

Victoria Liere

2017-09-01

Full Text Available Hepatic encephalopathy describes the array of neurological alterations that occur during acute liver failure or chronic liver injury. While key players in the pathogenesis of hepatic encephalopathy, such as increases in brain ammonia, alterations in neurosteroid levels, and neuroinflammation, have been identified, there is still a paucity in our knowledge of the precise pathogenic mechanism. This review gives a brief overview of our understanding of the pathogenesis of hepatic encephalopathy and then summarizes the significant recent advances made in clinical and basic research contributing to our understanding, diagnosis, and possible treatment of hepatic encephalopathy. A literature search using the PubMed database was conducted in May 2017 using “hepatic encephalopathy” as a keyword, and selected manuscripts were limited to those research articles published since May 2014. While the authors acknowledge that many significant advances have been made in the understanding of hepatic encephalopathy prior to May 2014, we have limited the scope of this review to the previous three years only.

Safety, efficacy, and patient acceptability of rifaximin for hepatic encephalopathy

DEFF Research Database (Denmark)

Kimer, Nina; Krag, Aleksander; Gluud, Lise L

2014-01-01

Hepatic encephalopathy is a complex disease entity ranging from mild cognitive dysfunction to deep coma. Traditionally, treatment has focused on a reduction of ammonia through a reduced production, absorption, or clearance. Rifaximin is a nonabsorbable antibiotic, which reduces the production of ...... and safety of long-term treatment with rifaximin and evaluate effects of combination therapy with lactulose and branched-chain amino acids for patients with liver cirrhosis and hepatic encephalopathy.......Hepatic encephalopathy is a complex disease entity ranging from mild cognitive dysfunction to deep coma. Traditionally, treatment has focused on a reduction of ammonia through a reduced production, absorption, or clearance. Rifaximin is a nonabsorbable antibiotic, which reduces the production...... of ammonia by gut bacteria and, to some extent, other toxic derivatives from the gut. Clinical trials show that these effects improve episodes of hepatic encephalopathy. A large randomized trial found that rifaximin prevents recurrent episodes of hepatic encephalopathy. Most patients were treated...

Wernicke encephalopathy in a patient with liver failure: Clinical case report.

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Zhao, Pan; Zhao, Yanling; Wei, Zhenman; Chen, Jing; Yan, Lilong

2016-07-01

Early recognition and diagnosis of Wernicke encephalopathy is pivotal for the prognosis of this medical emergency, especially in patients with liver failure which predisposes individuals to develop hepatic encephalopathy. For these patients, distinguishing between hepatic encephalopathy and Wernicke encephalopathy is a challenge in real-world clinical practice.A male patient with 21-year medical history of liver cirrhosis presented diarrhea and ascites. One month before this visit, he was noted to have poor appetite and progressive fatigue. After admission, although several major symptoms, including diarrhea, ascites, hyponatremia, and hypoproteinemia, were greatly improved through appropriate treatments, his laboratory indicators were not changed much. His appetite was not reversed at discharge. On the 5th day after discharge, the patient suddenly became reluctant to speak and did not remember the recent happenings. Simultaneously, unsteady gait and strabismus occurred. On the basis of clinical manifestations and brain magnetic resonance imaging scan results, the patient was diagnosed as Wernicke encephalopathy and these relative symptoms were resolved after intravenous vitamin B1.To our knowledge, this is the second case report of Wernicke encephalopathy developing in a critically ill cirrhotic patient without hepatocellular carcinoma or operative intervention. Wernicke encephalopathy may be underdiagnosed in these patients and this case raises physicians' awareness of its possible onset.

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

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

1995-01-01

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

Need for early diagnosis of mental and mobility changes in Wernicke encephalopathy.

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Wijnia, Jan W; Oudman, Erik; Bresser, Esmay L; Gerridzen, Ineke J; van de Wiel, Albert; Beuman, Carla; Mulder, Cornelis L

2014-12-01

Korsakoff syndrome is a chronic form of amnesia resulting from thiamine deficiency. The syndrome can develop from unrecognized or undertreated Wernicke encephalopathy. The intra-individual course of Wernicke-Korsakoff syndrome has not been studied extensively, nor has the temporal progression of gait disturbances and other symptoms of Wernicke encephalopathy. Here we present the detailed history of a patient whose acute symptoms of Wernicke encephalopathy were far from stable. We follow his mobility changes and the shifts in his mental status from global confusion and impaired consciousness to more selective cognitive deficits. His Wernicke encephalopathy was missed and left untreated, being labeled as "probable" Korsakoff syndrome. Patients with a history of self-neglect and alcohol abuse, at risk of or suffering with Wernicke encephalopathy, should receive immediate and adequate vitamin replacement. Self-neglecting alcoholics who are bedridden may have severe illness and probably active Wernicke encephalopathy. In these patients, mobility changes, delirium, or impaired consciousness can be an expression of Wernicke encephalopathy, and should be treated to prevent further damage from the neurologic complications of thiamine deficiency.

MRI findings in acute hyperammonemic encephalopathy resulting from decompensated chronic liver disease.

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Sureka, Jyoti; Jakkani, Ravi Kanth; Panwar, Sanuj

2012-06-01

Hyperammonemic encephalopathy is a type of metabolic encephalopathy with diversified etiology. Hyperammonemia is the end result of several metabolic disorders such as congenital deficiencies of urea cycle enzymes, hepatic encephalopathy, Reye's syndrome and other toxic encephalopathies. Non-specific clinical presentation poses a great challenge in early diagnosis of this entity. Irrespective of the underlying etiology, hyperammonemia causes a distinctive pattern of brain parenchymal injury. The cingulate gyrus and insular cortex are more vulnerable to this type of toxic insult. Characteristic magnetic resonance imaging findings in combination with laboratory parameters can help to differentiate this entity from other metabolic encephalopathy and thus aiding in early diagnosis and treatment.

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

International Nuclear Information System (INIS)

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

1999-01-01

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

77 FR 29914 - Bovine Spongiform Encephalopathy; Importation of Bovines and Bovine Products

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2012-05-21

... Spongiform Encephalopathy; Importation of Bovines and Bovine Products AGENCY: Animal and Plant Health... derived from bovines with regard to bovine spongiform encephalopathy. This action will allow interested... importation of live bovines and products derived from bovines with regard to bovine spongiform encephalopathy...

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

Directory of Open Access Journals (Sweden)

Madasamy Thangamuthu

2018-03-01

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

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

Science.gov (United States)

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

2018-03-07

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

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

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

2016-02-28

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

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

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

2017-07-01

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

Flumazenil versus placebo or no intervention for people with cirrhosis and hepatic encephalopathy

DEFF Research Database (Denmark)

Goh, Ee Teng; Andersen, Mette L.; Morgan, Marsha Y.

2017-01-01

Background: Hepatic encephalopathy is a common complication of cirrhosis which results in poor brain functioning. The spectrum of changes associated with hepatic encephalopathy ranges from the clinically 'indiscernible' or minimal hepatic encephalopathy to the clinically 'obvious' or overt hepatic...... encephalopathy. Flumazenil is a synthetic benzodiazepine antagonist with high affinity for the central benzodiazepine recognition site. Flumazenil may benefit people with hepatic encephalopathy through an indirect negative allosteric modulatory effect on gamma-aminobutyric acid receptor function. The previous...... version of this review, which included 13 randomised clinical trials, found no effect of flumazenil on all-cause mortality, based on an analysis of 10 randomised clinical trials, but found a beneficial effect on hepatic encephalopathy, based on an analysis of eight randomised clinical trials. Objectives...

Evaluation of the zoonotic potential of transmissible mink encephalopathy

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Successful transmission of Transmissible Mink Encephalopathy (TME) to cattle supports the bovine hypothesis to the still controversial origin of TME outbreaks. Human and primate susceptibility to classical Bovine Spongiform Encephalopathy (c-BSE) and the transmissibility of L-type BSE to macaques as...

Branched-chain amino acids for people with hepatic encephalopathy

DEFF Research Database (Denmark)

Gluud, Lise Lotte; Dam, Gitte; Les, Iñigo

2015-01-01

-chain amino acids (BCAA) versus control interventions has evaluated if BCAA may benefit people with hepatic encephalopathy. OBJECTIVES: To evaluate the beneficial and harmful effects of BCAA versus any control intervention for people with hepatic encephalopathy. SEARCH METHODS: We identified trials through...

Branched-chain amino acids for people with hepatic encephalopathy

DEFF Research Database (Denmark)

Gluud, Lise Lotte; Dam, Gitte; Les, Iñigo

2017-01-01

-chain amino acids (BCAA) versus control interventions has evaluated if BCAA may benefit people with hepatic encephalopathy. Objectives: To evaluate the beneficial and harmful effects of BCAA versus any control intervention for people with hepatic encephalopathy. Search methods: We identified trials through...

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

Science.gov (United States)

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

2016-02-01

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

Maternal or neonatal infection: association with neonatal encephalopathy outcomes.

Science.gov (United States)

Jenster, Meike; Bonifacio, Sonia L; Ruel, Theodore; Rogers, Elizabeth E; Tam, Emily W; Partridge, John Colin; Barkovich, Anthony James; Ferriero, Donna M; Glass, Hannah C

2014-07-01

Perinatal infection may potentiate brain injury among children born preterm. The objective of this study was to examine whether maternal and/or neonatal infection are associated with adverse outcomes among term neonates with encephalopathy. This study is a cohort study of 258 term newborns with encephalopathy whose clinical records were examined for signs of maternal infection (chorioamnionitis) and infant infection (sepsis). Multivariate regression was used to assess associations between infection, pattern, and severity of injury on neonatal magnetic resonance imaging, as well as neurodevelopment at 30 mo (neuromotor examination, or Bayley Scales of Infant Development, second edition mental development index encephalopathy, chorioamnionitis was associated with a lower risk of brain injury and adverse outcomes, whereas signs of neonatal sepsis carried an elevated risk. The etiology of encephalopathy and timing of infection and its associated inflammatory response may influence whether infection potentiates or mitigates injury in term newborns.

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

International Nuclear Information System (INIS)

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

2016-01-01

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

CT and MR in non-neonatal hypoxic-ischemic encephalopathy: radiological findings with pathophysiological correlations

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Gutierrez, Leonardo Guilhermino; Portela, Luiz Antonio Pezzi [Hospital Alemao Oswaldo Cruz and Hospital do Coracao, Diagnostic Imaging Division, Sao Paulo (Brazil); Rovira, Alex [University Hospital Vall d' Hebron, MR Unit, Department of Radiology, Barcelona (Spain); Costa Leite, Claudia da [Clinics Hospital of the University of Sao Paulo, School of Medicine, Department of Radiology, Sao Paulo (Brazil); Lucato, Leandro Tavares [Hospital Alemao Oswaldo Cruz and Hospital do Coracao, Diagnostic Imaging Division, Sao Paulo (Brazil); Clinics Hospital of the University of Sao Paulo, School of Medicine, Department of Radiology, Sao Paulo (Brazil)

2010-11-15

Non-neonatal hypoxic-ischemic encephalopathy is a clinical condition often related to cardiopulmonary arrest that demands critical management and treatment decisions. Management depends mainly on the degree of neurological impairment and prognostic considerations. Computed tomography (CT) is often used to exclude associated or mimicking pathology. If any, only nonspecific signs such as cerebral edema, sulci effacement, and decreased gray matter (GM)/white matter (WM) differentiation are evident. Pseudosubarachnoid hemorrhage, a GM/WM attenuation ratio <1.18, and inverted GM attenuation are associated with a poor prognosis. Magnetic resonance (MR) imaging is more sensitive than CT in assessing brain damage in hypoxic-ischemic encephalopathy. Some MR findings have similarities to those seen pathologically, based on spatial distribution and time scale, such as lesions distributed in watershed regions and selective injury to GM structures. In the acute phase, lesions are better depicted using diffusion-weighted imaging (DWI) because of the presence of cytotoxic edema, which, on T2-weighted images, only become apparent later in the early subacute phase. In the late subacute phase, postanoxic leukoencephalopathy and contrast enhancement could be observed. In the chronic phase, atrophic changes predominate over tissue signal changes. MR can be useful for estimating prognosis when other tests are inconclusive. Some findings, such as the extent of lesions on DWI and presence of a lactate peak and depleted N-acetyl aspartate peak on MR spectroscopy, seem to have prognostic value. (orig.)

CT and MR in non-neonatal hypoxic-ischemic encephalopathy: radiological findings with pathophysiological correlations

International Nuclear Information System (INIS)

Gutierrez, Leonardo Guilhermino; Portela, Luiz Antonio Pezzi; Rovira, Alex; Costa Leite, Claudia da; Lucato, Leandro Tavares

2010-01-01

Non-neonatal hypoxic-ischemic encephalopathy is a clinical condition often related to cardiopulmonary arrest that demands critical management and treatment decisions. Management depends mainly on the degree of neurological impairment and prognostic considerations. Computed tomography (CT) is often used to exclude associated or mimicking pathology. If any, only nonspecific signs such as cerebral edema, sulci effacement, and decreased gray matter (GM)/white matter (WM) differentiation are evident. Pseudosubarachnoid hemorrhage, a GM/WM attenuation ratio <1.18, and inverted GM attenuation are associated with a poor prognosis. Magnetic resonance (MR) imaging is more sensitive than CT in assessing brain damage in hypoxic-ischemic encephalopathy. Some MR findings have similarities to those seen pathologically, based on spatial distribution and time scale, such as lesions distributed in watershed regions and selective injury to GM structures. In the acute phase, lesions are better depicted using diffusion-weighted imaging (DWI) because of the presence of cytotoxic edema, which, on T2-weighted images, only become apparent later in the early subacute phase. In the late subacute phase, postanoxic leukoencephalopathy and contrast enhancement could be observed. In the chronic phase, atrophic changes predominate over tissue signal changes. MR can be useful for estimating prognosis when other tests are inconclusive. Some findings, such as the extent of lesions on DWI and presence of a lactate peak and depleted N-acetyl aspartate peak on MR spectroscopy, seem to have prognostic value. (orig.)

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

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

2012-07-01

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

Genetics Home Reference: glycine encephalopathy

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... seizures. As they get older, many develop intellectual disability, abnormal movements, and behavioral problems. Other atypical types of glycine encephalopathy appear later in childhood or adulthood ...

Determination of lactic acid level in systemic liquids in children with progressive encephalopathies.

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Marszał, Elzbieta; Wojaczyńska-Stanek, Katarzyna; Pietruszewski, Jerzy; Emich-Widera, Ewa; Bielińska-Bujniewicz, Eugenia

2002-03-01

This article reports the results of research into the activities of lactic acid concentrations in the body fluids of children with progressive encephalopathies (PE) in comparison to patients with non-progressive encephalopathies (NPE) and those with non-progressive encephalopathies with concomitant epilepsy (NPEE). The study was designed to determine whether there is difference between the serum and CSF lactic acid concentrations in children with progressive encephalopathies (PE), static (non-progressive) encephalopathies (NPE) and non progressive encephalopathies with concomitant epilepsy (NPEE), and whether the clinical status correlates with the concentration of these biochemical markers in children with PE. The assessment involved 138 children of both sexes, whose age ranged between 8 months and 15 years, diagnosed and treated in the Neurology Department at the Pediatric Clinic of the Silesian Medical Academy in Katowice between 1995 and 1997. Lactate concentrations were determined in serum and cerebro-spinal fluid and analyzed statistically. The findings showed higher serum and CSF concentrations in children with PE than in patients who manifested non-progressive forms of encephalopathy. The degree of clinical symptom aggravation in PE children was likewise analyzed and compared to the values of lactate concentrations in body fluids; however, no correlation was found between these parameters. Children with progressive encephalopathies present higher lactate concentrations in serum and cerebrospinal fluid than patients with static (non-progressive) encephalopathy.

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

International Nuclear Information System (INIS)

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

1986-01-01

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

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

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

1986-12-15

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

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

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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.

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

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Silvia Gazzin

2011-01-01

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

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

NARCIS (Netherlands)

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

2014-01-01

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

Neonatal encephalopathy and socioeconomic status: population-based case-control study.

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Blume, Heidi K; Loch, Christian M; Li, Christopher I

2007-07-01

To investigate the association between maternal socioeconomic status and the risk of encephalopathy in full-term newborns. Population-based case-control study. Washington State births from 1994 through 2002 recorded in the linked Washington State Birth Registry and Comprehensive Hospital Abstract Reporting System. Cases (n = 1060) were singleton full-term newborns with Comprehensive Hospital Abstract Reporting System International Classification of Diseases, Ninth Revision diagnoses of seizures, birth asphyxia, central nervous system dysfunction, or cerebral irritability. Control cases (n = 5330) were singleton full-term newborns selected from the same database. Main Exposures Socioeconomic status was defined by median income of the census tract of the mother's residence, number of years of maternal educational achievement, or maternal insurance status. Odds ratios estimating the risk of encephalopathy associated with disadvantaged socioeconomic status were calculated in 3 separate analyses using multivariate adjusted logistic regression. Newborns of mothers living in neighborhoods in which residents have a low median income were at increased risk of encephalopathy compared with newborns in neighborhoods in which residents have a median income more than 3 times the poverty level (adjusted odds ratio, 1.9; 95% confidence interval, 1.5-2.3). There was also a trend for increasing risk of encephalopathy associated with decreasing neighborhood income (PNewborns of mothers with less than 12 years of educational achievement had a higher risk of encephalopathy compared with newborns of mothers with more than 16 years of educational achievement (adjusted odds ratio, 1.7; 95% confidence interval, 1.3-2.3). Newborns of mothers receiving public insurance also had a higher risk of encephalopathy compared with newborns of mothers who have commercial insurance (adjusted odds ratio, 1.4; 95% confidence interval, 1.2-1.7). Disadvantaged socioeconomic status was independently

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

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Neha Dhungana

2017-08-01

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

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

International Nuclear Information System (INIS)

Jin Gu; Yao Qizhi; Zhang Shanzi; Zhang Lei

2008-01-01

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

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

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

2017-09-01

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

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

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Eghbalian, Fatemeh; Rafienezhad, Haneyeh; Farmal, Javad

2017-11-01

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

Hepatic Encephalopathy: Early Diagnosis in Pediatric Patients With Cirrhosis

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DARA, Naghi; SAYYARI, Ali-Akbar; IMANZADEH, Farid

2014-01-01

Objective As acute liver failure (ALF) and chronic liver disease (cirrhosis) continue to increase in prevalence, we will see more cases of hepatic encephalopathy. Primary care physician are often the first to suspect it, since they are familiar with the patient’s usual physical and mental status. This serious complication typically occurs in patients with severe comorbidities and needs multidisciplinary evaluation and care. Hepatic encephalopathy should be considered in any patient with acute liver failure and cirrhosis who presents with neuropsychiatric manifestations, decrease level of consciousness (coma), change of personality, intellectual and behavioral deterioration, speech and motor dysfunction. Every cirrhotic patient may be at risk; potential precipitating factors should be addressed in regular clinic visits. The encephalopathy of liver disease may be prominent, or can be present in subtle forms, such as decline of school performance, emotional outbursts, or depression. “Subtle form” of hepatic encephalopathy may not be obvious on clinical examination, but can be detected by neurophysiologic and neuropsychiatric testing. PMID:24665321

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

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

2014-01-01

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

Stimulus induced bursts in severe postanoxic encephalopathy.

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Tjepkema-Cloostermans, Marleen C; Wijers, Elisabeth T; van Putten, Michel J A M

2016-11-01

To report on a distinct effect of auditory and sensory stimuli on the EEG in comatose patients with severe postanoxic encephalopathy. In two comatose patients admitted to the Intensive Care Unit (ICU) with severe postanoxic encephalopathy and burst-suppression EEG, we studied the effect of external stimuli (sound and touch) on the occurrence of bursts. In patient A bursts could be induced by either auditory or sensory stimuli. In patient B bursts could only be induced by touching different facial regions (forehead, nose and chin). When stimuli were presented with relatively long intervals, bursts persistently followed the stimuli, while stimuli with short intervals (encephalopathy can be induced by external stimuli, resulting in stimulus-dependent burst-suppression. Stimulus induced bursts should not be interpreted as prognostic favourable EEG reactivity. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Metformin inhibits glutaminase activity and protects against hepatic encephalopathy.

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Javier Ampuero

Full Text Available AIM: To investigate the influence of metformin use on liver dysfunction and hepatic encephalopathy in a retrospective cohort of diabetic cirrhotic patients. To analyze the impact of metformin on glutaminase activity and ammonia production in vitro. METHODS: Eighty-two cirrhotic patients with type 2 diabetes were included. Forty-one patients were classified as insulin sensitizers experienced (metformin and 41 as controls (cirrhotic patients with type 2 diabetes mellitus without metformin treatment. Baseline analysis included: insulin, glucose, glucagon, leptin, adiponectin, TNFr2, AST, ALT. HOMA-IR was calculated. Baseline HE risk was calculated according to minimal hepatic encephalopathy, oral glutamine challenge and mutations in glutaminase gene. We performed an experimental study in vitro including an enzymatic activity assay where glutaminase inhibition was measured according to different metformin concentrations. In Caco2 cells, glutaminase activity inhibition was evaluated by ammonia production at 24, 48 and 72 hours after metformina treatment. RESULTS: Hepatic encephalopathy was diagnosed during follow-up in 23.2% (19/82: 4.9% (2/41 in patients receiving metformin and 41.5% (17/41 in patients without metformin treatment (logRank 9.81; p=0.002. In multivariate analysis, metformin use [H.R.11.4 (95% CI: 1.2-108.8; p=0.034], age at diagnosis [H.R.1.12 (95% CI: 1.04-1.2; p=0.002], female sex [H.R.10.4 (95% CI: 1.5-71.6; p=0.017] and HE risk [H.R.21.3 (95% CI: 2.8-163.4; p=0.003] were found independently associated with hepatic encephalopathy. In the enzymatic assay, glutaminase activity inhibition reached 68% with metformin 100 mM. In Caco2 cells, metformin (20 mM decreased glutaminase activity up to 24% at 72 hours post-treatment (p<0.05. CONCLUSIONS: Metformin was found independently related to overt hepatic encephalopathy in patients with type 2 diabetes mellitus and high risk of hepatic encephalopathy. Metformin inhibits glutaminase

Chronic traumatic encephalopathy: contributions from the Boston University Center for the Study of Traumatic Encephalopathy.

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Riley, David O; Robbins, Clifford A; Cantu, Robert C; Stern, Robert A

2015-01-01

Chronic Traumatic Encephalopathy (CTE) is a neurodegenerative disease associated with repetitive brain trauma (RBT). Initially described in boxers, CTE has now been found in other contact sport athletes with a history of RBT. In recent years, there has been tremendous media attention regarding CTE, primarily because of the deaths of high profile American football players who were found to have CTE upon neuropathological examination. However, the study of CTE remains in its infancy. This review focuses on research from the Centre for the Study of Traumatic Encephalopathy (CSTE) at Boston University. This study reviews the formation of the CSTE, major CSTE publications and current ongoing research projects at the CSTE. The neuropathology of CTE has been well-described. Current research focuses on: methods of diagnosing the disease during life (including the development of biomarkers), examination of CTE risk factors (including genetic susceptibility and head impact exposure variables); description of the clinical presentation of CTE; development of research diagnostic criteria for Traumatic Encephalopathy Syndrome; and assessment of mechanism and pathogenesis. Current research at the BU CSTE is aimed at increasing understanding of the long-term consequences of repetitive head impacts and attempting to begin to answer several of the unanswered questions regarding CTE.

Genetics Home Reference: SCN8A-related epilepsy with encephalopathy

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... Resources (6 links) Boston Children's Hospital: Epilepsy and Seizure Disorder in Children Centers for Disease Control and Prevention: ... related epilepsy with encephalopathy Merck Manual Consumer Version: Seizure Disorders Orphanet: Early infantile epileptic encephalopathy Patient Support and ...

Novel diode-based laser system for combined transcutaneous monitoring and computer-controlled intermittent treatment of jaundiced neonates

Science.gov (United States)

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.

Current concepts in the assessment and treatment of hepatic encephalopathy.

LENUS (Irish Health Repository)

Cash, W J

2012-02-01

Hepatic encephalopathy (HE) is defined as a metabolically induced, potentially reversible, functional disturbance of the brain that may occur in acute or chronic liver disease. Standardized nomenclature has been proposed but a standardized approach to the treatment, particularly of persistent, episodic and recurrent encephalopathy associated with liver cirrhosis has not been proposed. This review focuses on the pathogenesis and treatment of HE in patients with cirrhosis. The pathogenesis and treatment of hepatic encephalopathy in fulminant hepatic failure is quite different and is reviewed elsewhere.

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

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

2017-03-01

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

Brain hypothermia therapy for childhood acute encephalopathy based on clinical evidence

OpenAIRE

IMATAKA, GEORGE; ARISAKA, OSAMU

2015-01-01

Although previous studies have reported on the effectiveness of brain hypothermia therapy in childhood acute encephalopathy, additional studies in this field are necessary. In this review, we discussed brain hypothermia therapy methods for two clinical conditions for which sufficient evidences are currently available in the literature. The first condition is known as hypoxic-ischemic encephalopathy and occurs in newborns and the second condition is acute encephalopathy which occurs in adults ...

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

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

1994-05-10

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

Seeing more clearly through the fog of encephalopathy.

Science.gov (United States)

Kaplan, Peter W; Sutter, Raoul

2013-10-01

Patients with acute confusional states (often referred to as encephalopathy or delirium) pose diagnostic and management challenges for treating physicians. Encephalopathy is associated with a high morbidity and mortality rate, and the diagnosis rests on clinical grounds but may also be supported by the finding of electroencephalographic (EEG) evidence for diffuse cerebral dysfunction. The myriad cerebral transmitter and metabolic disruptions are generated by systemic organ system failures, principal among which are those of the liver, kidneys, lungs, heart, and endocrine system, along with the effects of exogenous toxins and medications. In most cases, several of these organ failures together contribute to the confusional state, frequently in the context of a diffuse cerebral atrophy that affects the aging brain. This special issue of the Journal of Clinical Neurophysiology is dedicated to exploring the electrophysiology of these conditions. It reviews the pathophysiology, psychiatric manifestations, clinical and imaging correlations of the many causes and types of encephalopathy. A literature review of the EEG abnormalities in the various types of encephalopathy provides an overview that ranges from paraneoplastic causes, through organ system failures, postcardiorespiratory arrest, to postoperative delirium. The issue is supplemented by tables of relevant clinical correlations, graphs, Venn diagrams, and the use of mathematical modeling used to explain how defects in the neuronal interplay might generate the EEG patterns seen in encephalopathy. We hope that this assembly will act as a springboard for further discussion and investigation into the EEG underpinnings, clinical correlations, diagnosis. and prognostication of these common and morbid disturbances of brain function.

Transient dysautonomia in an acute phase of encephalopathy with biphasic seizures and late reduced diffusion.

Science.gov (United States)

Ichimiya, Yuko; Kaku, Noriyuki; Sakai, Yasunari; Yamashita, Fumiya; Matsuoka, Wakato; Muraoka, Mamoru; Akamine, Satoshi; Mizuguchi, Soichi; Torio, Michiko; Motomura, Yoshitomo; Hirata, Yuichiro; Ishizaki, Yoshito; Sanefuji, Masafumi; Torisu, Hiroyuki; Takada, Hidetoshi; Maehara, Yoshihiko; Ohga, Shouichi

2017-08-01

Paroxysmal sympathetic hyperactivity (PSH) is a dysautonomic condition that is associated with various types of acquired brain injuries. Traumatic brain lesions have been documented as the leading cause of PSH. However, detailed clinical features of pediatric PSH caused by intrinsic brain lesions remain to be elusive. We present a 3-year-old boy, who had been diagnosed as having cerebral palsy, developmental delay and epilepsy after perinatal hypoxia-induced brain injury. He developed status epilepticus with fever on the third day of respiratory infection. Whereas the seizure was terminated by systemic infusion of midazolam, consciousness remained disturbed for the next 48h. Serial magnetic resonance imaging studies revealed that acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) evolved on 3days after the seizure. Therapeutic hypothermia was immediately introduced, however, the brain lesion extended to the whole subcortical white matters on day 8. The intermittent bilateral dilation of pupils with increased blood pressure and tachycardia were observed until day 12. Real-time monitoring of electroencephalograms ruled out the recurrent attacks of seizures. The abnormal signs of autonomic nervous system gradually ceased and never relapsed after recovery from the hypothermia. PSH or a transient condition of dysautonomia may emerge and persist during the acute phase of AESD. Copyright © 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Acute hepatic encephalopathy with diffuse cortical lesions

Energy Technology Data Exchange (ETDEWEB)

Arnold, S.M.; Spreer, J.; Schumacher, M. [Section of Neuroradiology, Univ. of Freiburg (Germany); Els, T. [Dept. of Neurology, University of Freiburg (Germany)

2001-07-01

Acute hepatic encephalopathy is a poorly defined syndrome of heterogeneous aetiology. We report a 49-year-old woman with alcoholic cirrhosis and hereditary haemorrhagic telangiectasia who developed acute hepatic coma induced by severe gastrointestinal bleeding. Laboratory analysis revealed excessively elevated blood ammonia. MRI showed lesions compatible with chronic hepatic encephalopathy and widespread cortical signal change sparing the perirolandic and occipital cortex. The cortical lesions resembled those of hypoxic brain damage and were interpreted as acute toxic cortical laminar necrosis. (orig.)

Acute hepatic encephalopathy with diffuse cortical lesions

International Nuclear Information System (INIS)

Arnold, S.M.; Spreer, J.; Schumacher, M.; Els, T.

2001-01-01

Acute hepatic encephalopathy is a poorly defined syndrome of heterogeneous aetiology. We report a 49-year-old woman with alcoholic cirrhosis and hereditary haemorrhagic telangiectasia who developed acute hepatic coma induced by severe gastrointestinal bleeding. Laboratory analysis revealed excessively elevated blood ammonia. MRI showed lesions compatible with chronic hepatic encephalopathy and widespread cortical signal change sparing the perirolandic and occipital cortex. The cortical lesions resembled those of hypoxic brain damage and were interpreted as acute toxic cortical laminar necrosis. (orig.)

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

Science.gov (United States)

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

2016-05-01

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

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

Science.gov (United States)

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

2017-04-01

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

Performance of the hepatic encephalopathy scoring algorithm in a clinical trial of patients with cirrhosis and severe hepatic encephalopathy

DEFF Research Database (Denmark)

Hassanein, T.; Blei, A.T.; Perry, W.

2009-01-01

OBJECTIVES: The grading of hepatic encephalopathy (HE) is based on a combination of indicators that reflect the state of consciousness, intellectual function, changes in behavior, and neuromuscular alterations seen in patients with liver failure. METHODS: We modified the traditional West Haven...... criteria (WHC) to provide an objective assessment of the cognitive parameters to complement the subjective clinical ratings for the performance of extracorporeal albumin dialysis (ECAD) using a molecular adsorption recirculating system in patients with cirrhosis and severe (grade III / IV) encephalopathy...

Investigation of metabolic encephalopathy

African Journals Online (AJOL)

cycle defects is the X-linked recessive disorder, ornithine ... life, or if the child is fed the compounds that they are unable .... as learning difficulties, drowsiness and avoidance of ... Table 2. Laboratory investigation of suspected metabolic encephalopathy. Laboratory .... Clinical approach to treatable inborn metabolic diseases:.

GRIN2B encephalopathy

DEFF Research Database (Denmark)

Platzer, Konrad; Yuan, Hongjie; Schuetz, Hannah

2017-01-01

BACKGROUND: We aimed for a comprehensive delineation of genetic, functional and phenotypic aspects of GRIN2B encephalopathy and explored potential prospects of personalised medicine. METHODS: Data of 48 individuals with de novo GRIN2B variants were collected from several diagnostic and research c...

Benzodiazepine receptor antagonists for acute and chronic hepatic encephalopathy

DEFF Research Database (Denmark)

Als-Nielsen, B; Kjaergard, L L; Gluud, C

2001-01-01

The pathogenesis of hepatic encephalopathy is unknown. It has been suggested that liver failure leads to the accumulation of substances that bind to a receptor-complex in the brain resulting in neural inhibition which may progress to coma. Several trials have assessed benzodiazepine receptor...... antagonists for hepatic encephalopathy, but the results are conflicting....

Newborns Referred for Therapeutic Hypothermia: Association between Initial Degree of Encephalopathy and Severity of Brain Injury (What About the Newborns with Mild Encephalopathy on Admission?).

Science.gov (United States)

Gagne-Loranger, Maude; Sheppard, Megan; Ali, Nabeel; Saint-Martin, Christine; Wintermark, Pia

2016-01-01

The aim of this article was to describe the severity of brain injury and/or mortality in a cohort of newborns referred for therapeutic hypothermia, in relation to the degree of encephalopathy on admission, and to especially look at the ones with initial mild encephalopathy. Term newborns with perinatal depression referred to our neonatal intensive care unit for possible hypothermia treatment from 2008 to 2012 were enrolled prospectively. The modified Sarnat score on admission was correlated with severity of brain injury on brain imaging and/or autopsy. A total of 215 newborns were referred for possible cooling. Sixty percent (128/215) were cooled. Most of the not-cooled newborns with an available brain magnetic resonance imaging (85% = 50/59) had an initial mild encephalopathy, and 40% (20/50) developed brain injury. Some cooled newborns had an initial mild encephalopathy (12% = 13/108); only 31% (4/13) developed brain injury. Our results demonstrated that several newborns with an initial mild encephalopathy developed subsequent brain injury, especially when they were not cooled. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

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

Science.gov (United States)

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

2010-12-01

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

The ketogenic diet can be used successfully in combination with corticosteroids for epileptic encephalopathies.

Science.gov (United States)

Ville, Dorothée; Chiron, Catherine; Laschet, Jacques; Dulac, Olivier

2015-07-01

Hormonal therapy or ketogenic diet often permits overcoming the challenging periods of many epileptic encephalopathies (West and Lennox-Gastaut syndromes and encephalopathy with continuous spike-waves in slow sleep), but relapse affects over 20% of patients. We report here a monocenter pilot series of 42 consecutive patients in whom we combined oral steroids with the ketogenic diet for corticosteroid-resistant or -dependent epileptic encephalopathy. We retrospectively evaluated the effect on seizure frequency, interictal spike activity, neuropsychological course, and steroid treatment course. Twenty-three patients had West syndrome (WS), 13 had encephalopathy with continuous spike-waves in slow sleep (CSWS), and six others had miscellaneous epileptic encephalopathies. All patients succeeded to reach 0.8 to 1.6g/l ketone bodies in the urine following the usual KD regimen. For at least 6 months, 14/42 responded to the addition of the ketogenic diet: 4/23 with WS, 8/13 with CSWS, and 2/6 with miscellaneous epileptic encephalopathies. The addition of the KD allowed withdrawing steroids in all responders. Among them, 10/15 had been patients with steroid-dependent epileptic encephalopathy and 4/27 patients with steroid-resistant epileptic encephalopathy. Therefore, the ketogenic diet can be used successfully in combination with corticosteroids for epileptic encephalopathies. Patients presenting with steroid-dependent CSWS seem to be the best candidates. Copyright © 2015 Elsevier Inc. All rights reserved.

Nationwide survey of rotavirus-associated encephalopathy and sudden unexpected death in Japan.

Science.gov (United States)

Kawamura, Yoshiki; Ohashi, Masahiro; Ihira, Masaru; Hashimoto, Shuji; Taniguchi, Koki; Yoshikawa, Tetsushi

2014-08-01

Rotavirus can cause severe complications such as encephalopathy/encephalitis and sudden unexpected death. The incidence of rotavirus-associated encephalopathy/encephalitis or sudden unexpected death remains unknown. To clarify the clinical features of rotavirus-associated encephalitis/encephalopathy and sudden unexpected death, we conducted a nationwide survey in Japan. A two-part questionnaire was designed to determine the number of the cases and the clinical features of severe cases of rotavirus infection, including encephalitis/encephalopathy and sudden unexpected death, between 2009 and 2011. Of the 1365 questionnaires sent to hospitals, 963 (70.5%) were returned and eligible for analysis. We determined 58 cases of rotavirus-associated encephalitis/encephalopathy and 7 cases of sudden unexpected death. These patients were diagnosed with rotavirus infection by immunochromatography. Although 36/58 (62.1%) encephalitis/encephalopathy patients had no sequelae, 15/58 (25.9%) patients had neurological sequelae, and 7/58 (12.1%) patients had fatal outcomes. Pleocytosis was observed in 9/40 (22.5%) patients and cerebrospinal fluid protein levels were elevated in only 4/40 (10%) patients. Elevated lactate dehydrogenase (LDH) (>500 IU/L) or acidemia (pHdeath were 44.0 and 4.9 cases in Japan, respectively. Elevated LDH (>500 IU/L) or acidemia (pH<7.15) were related to a poor prognosis of the encephalitis/encephalopathy. Copyright © 2013 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Hemorrhagic shock and encephalopathy syndrome: a case report

International Nuclear Information System (INIS)

Yoon, Sook Ja; Choi, Yun Sun; Shin, Chung Ho; Cho, Sung Bum; Cho, Jae Min; Kim, Hyun Sook; Han, Tae Il; Yoon, Yong Kyu

2001-01-01

Hemorrhagic shock and encephalopathy syndrome (HSES) is a sudden-onset symptom complex that involves multisystem failure and includes encephalopathy, shock, coma, convulsions, prerenal azotemia, hepatic dysfunction, and bleeding coagulopathy and progressive thrombocytopenia in previously healthy infants and children. Its radiologic findings have rarely been reported, and it has not been described in Korea. We present a case of clinically diagnosed HSES, and include the CT and MRI findings

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

Science.gov (United States)

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

2017-08-01

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

Risk factors and outcome of Shigella encephalopathy in Bangladeshi children.

Directory of Open Access Journals (Sweden)

Farzana Afroze

2017-04-01

Full Text Available Although, Shigella encephalopathy, a serious extra-intestinal complication of shigellosis, significantly increases the risks of death, data are very limited on predicting factors particularly related to electrolyte profiles in children below five years of age with Shigella encephalopathy. Our objective was to determine the clinical as well as laboratory predicting factors and outcome of children with Shigella encephalopathy.In this unmatched case-control design, children aged 2-59 months having a positive stool culture for Shigella and who had their serum electrolytes been done from July 2012 to June 2015 were studied. Children with Shigella encephalopathy, defined as having abnormal mentation, constituted the cases, and those without encephalopathy constituted the controls. During the study period, we identified a total of 541 children less than five years of age, who had Shigella in their stool culture. Only 139 children fulfilled the study criteria and among them 69 were cases and 70 were controls. The cases more often had fatal outcome compared to the controls (7% vs. 0%, P = 0.02. In logistic regression analysis, the cases were independently associated with shorter duration (1.2 ± 0.4 days of diarrhea prior to admission, dehydrating diarrhea, sepsis and hyponatremia (p<0.05 for all. Among 139 Shigella isolates, S. flexneri (88/139, 63% and S. sonnei(34/139, 24% were the dominant species. S. dysenteriae was not isolated throughout the study period. S.sonnei was more frequently isolated from the cases (24/69, 35% than the controls (10/70, 14%, whereas the isolation of S. flexneri was comparable between the groups (40/69, 58% vs 48/70, 69%. A total of 94 (67.6% isolates were resistant to trimethoprim-sulphamethoxazole, 84 (60.4% to ciprofloxacin, 66/138 (48% to ampicillin, 5 (3.5% to ceftriaxone, 17 (12.2% to mecillinum and 35 (25% to azithromycin.The case-fatality-rate was significantly higher among the children with Shigella encephalopathy

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

Directory of Open Access Journals (Sweden)

I. B. Zhakun

2017-12-01

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

Clinical utility of high b-value diffusion-weighted magnetic resonance imaging in post-resuscitative encephalopathy

International Nuclear Information System (INIS)

Kano, Hitoshi; Danjou, Wataru; Yamazaki, Kei

2002-01-01

It is very important to estimate brain functional capacity immediately after successful cardiopulmonary resuscitation (CPR) to determine subsequent treatment strategy and to elucidate the pathophysiology of patients with post-resuscitative encephalopathy. However, computed tomography scanning, electric encephalography and conventional magnetic resonance imaging do not contribute significantly to the assessment of brain functions immediately after CPR. Recently, diffusion-weighted magnetic resonance imaging (DW-MRI) has been applied to the patients with post-resuscitative encephalopathy. However, no papers have described serial clinical and repeated DW-MRI studies of patients during the acute phase of post-resuscitative encephalopathy. Moreover, in some cases, high signal intensity in the cortex after CPR is indistinguishable from normal cortex. Thus, we tried to apply high b-value DW-MRI to estimate the brain function of patients with post-resuscitative encephalopathy. This study was performed on 11 patients with post-resuscitative encephalopathy and 5 healthy volunteers as controls. DW-MRI was performed using GYROSCAN 1.5 Tesla MR imager (Philips) with single-shot echo-planner imaging sequences performed 3 times, first within 24 hours after CPR, second between day 3 to 6, and third more than 7 days after CPR. And we tested the usefulness of DW-MRI at 800, 1000, 1500, 2000 and 3000 in b value. Five patients survived, one fully recovered and four remained in a vegetative state. The other six died with clinical brain death. The first DW-MRI revealed in high signal intensity in the frontal and the parietal lobes in all patients who eventually progressed to a vegetative state or brain death. This result was much more wide-spread in the latter patients, while it was never seen in the patients who recovered fully. The high signal intensity areas increased in follow-up DW-MRI studies. The signal intensity remained high in some parts, while it decreased in other parts with

Clinical utility of high b-value diffusion-weighted magnetic resonance imaging in post-resuscitative encephalopathy

Energy Technology Data Exchange (ETDEWEB)

Kano, Hitoshi; Danjou, Wataru; Yamazaki, Kei [Sapporo City General Hospital (Japan)] (and others)

2002-03-01

It is very important to estimate brain functional capacity immediately after successful cardiopulmonary resuscitation (CPR) to determine subsequent treatment strategy and to elucidate the pathophysiology of patients with post-resuscitative encephalopathy. However, computed tomography scanning, electric encephalography and conventional magnetic resonance imaging do not contribute significantly to the assessment of brain functions immediately after CPR. Recently, diffusion-weighted magnetic resonance imaging (DW-MRI) has been applied to the patients with post-resuscitative encephalopathy. However, no papers have described serial clinical and repeated DW-MRI studies of patients during the acute phase of post-resuscitative encephalopathy. Moreover, in some cases, high signal intensity in the cortex after CPR is indistinguishable from normal cortex. Thus, we tried to apply high b-value DW-MRI to estimate the brain function of patients with post-resuscitative encephalopathy. This study was performed on 11 patients with post-resuscitative encephalopathy and 5 healthy volunteers as controls. DW-MRI was performed using GYROSCAN 1.5 Tesla MR imager (Philips) with single-shot echo-planner imaging sequences performed 3 times, first within 24 hours after CPR, second between day 3 to 6, and third more than 7 days after CPR. And we tested the usefulness of DW-MRI at 800, 1000, 1500, 2000 and 3000 in b value. Five patients survived, one fully recovered and four remained in a vegetative state. The other six died with clinical brain death. The first DW-MRI revealed in high signal intensity in the frontal and the parietal lobes in all patients who eventually progressed to a vegetative state or brain death. This result was much more wide-spread in the latter patients, while it was never seen in the patients who recovered fully. The high signal intensity areas increased in follow-up DW-MRI studies. The signal intensity remained high in some parts, while it decreased in other parts with

Research progress of BOLD-functional MRI of hepatic encephalopathy

International Nuclear Information System (INIS)

Ni Ling; Zhang Longjiang; Lu Guangming

2013-01-01

Hepatic encephalopathy (HE), characterized by a wide spectrum of clinical manifestations, ranging from behavior abnormality, conscious disorder and even coma, is a consequence of liver dysfunction in both acute and chronic hepatic diseases. Minimal hepatic encephalopathy (MHE) refers to a subgroup of cirrhotic patients without clinical overt hepatic encephalopathy symptoms hut with abnormalities in neuro -cognitive functions. HE/MHE can have a far-reaching impact on quality of life and prognosis. The exact neuropathology mechanism was still unclear. Recently, functional MRI (fMRI) has been increasingly applied for investigating the neuro-pathophysiological mechanism of HE. This paper will review the fMRI research applied on uncovering the neuropathology mechanism of HE. (authors)

Wernicke’s encephalopathy associated with liver abscess.

Science.gov (United States)

Verma, Rajesh; Garg, Vipul

2017-07-31

Wernicke's encephalopathy is a rare neurological disorder caused by thiamine deficiency, characterised by ocular motor dysfunction, ataxia and impairment in consciousness. It predominantly affects brain regions with a high metabolic rate such as mammillary bodies, medial thalamic nuclei, the tectal region and the cerebellum. Although chronic alcoholism is the most common cause of Wernicke's encephalopathy, various other conditions not related to alcohol consumption such as bariatric surgery, acute pancreatitis, hyperemesis gravidarum, prolonged fasting and gastrointestinal surgery have been implicated in its aetiology. We report the case of a patient who underwent surgery for liver abscess and subsequently developed Wernicke's encephalopathy; he showed a positive response to thiamine supplementation. This is the first report describing liver abscess as the cause of Wernicke's encephalopathy. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Celiac crisis presenting with status epilepticus and encephalopathy.

Science.gov (United States)

Hijaz, Nadia M; Bracken, Julia M; Chandratre, Sonal R

2014-12-01

Celiac crisis is a life-threatening presentation of celiac disease which is described in the context of classic gastrointestinal (GI) symptoms of diarrhea, leading to dehydration and electrolyte imbalance. Neurologic manifestations are atypical symptoms of celiac crisis. To the best of our knowledge, there is no published report on seizure or encephalopathy as the presenting manifestation of celiac crisis. We describe a 2-year-old boy presenting with acute status epilepticus and lethargy. Prior to presentation, he had mild abdominal distention and intermittent diarrhea. Laboratory analysis revealed hyponatremia, anemia, hypocalcemia, transaminitis, and hyperglycemia. Electroencephalography revealed severe diffuse encephalopathy, and complete infectious work-up was negative. Initial brain magnetic resonance imaging was normal; however, repeat imaging showed osmotic demyelination syndrome. Given the history of GI symptoms and hyperglycemia, celiac serology was obtained revealing elevated tissue transglutaminase, and a diagnosis was confirmed by Marsh 3c lesions in the duodenum. He significantly improved with steroid therapy in addition to adequate nutrition, fluids, and initiation of a gluten-free diet. We report herein on the first case of celiac crisis presenting with status epilepticus and encephalopathy in the absence of profound GI symptoms. Our case suggests that celiac crisis should be considered in the differential of seizures and encephalopathy in children.

Clinical and radiological features of hypertensive brainstem encephalopathy

Directory of Open Access Journals (Sweden)

Xiao-qiu LI

2015-07-01

Full Text Available Objective　To discuss the diagnosis and treatment of hypertensive brainstem encephalopathy. Methods　 The clinical and imaging data of 3 cases of hypertensive brainstem encephalopathy were summarized and analyzed for the purpose of improving the acumen in diagnosis and treatment. Results　All the 3 patients showed relatively mild clinical symptoms, and they were misdiagnosed in different degrees during the treatment, but their clinical symptoms were improved by rapid and effective antihypertensive therapy. Cerebral CT and MRI scans revealed extensive abnormal signals in brain stem, with or without supratentorial lesions and brain stem hemorrhage. The lesions as revealed by imaging were improved significantly after treatment. Conclusions　Clinical-radiographic dissociation is the classic feature of hypertensive brainstem encephalopathy. The clinical symptoms and lesions as shown by imaging could be improved after active treatment. DOI: 10.11855/j.issn.0577-7402.2015.06.03

Expression and role of neuroglobin in rats with sepsis-associated encephalopathy.

Science.gov (United States)

Zhang, Li-Na; Ai, Yu-Hang; Gong, Hua; Guo, Qu-Lian; Huang, Li; Liu, Zhi-Yong; Yao, Bo

2014-01-01

To determine the role of neuroglobin in the pathology of sepsis-associated encephalopathy and ascertain if neuroglobin has any protective effects against sepsis-associated encephalopathy. Randomized laboratory animal study. Research university animal laboratory. Two hundred and forty adult male Sprague-Dawley rats. Rats received cecal puncture and ligation (or sham) surgery to induce sepsis, then broken up into groups based on whether or not the rat developed sepsis-associated encephalopathy as determined by electroencephalograph and evoked potential recordings. The rats were then left untreated to examine the effect of sepsis-associated encephalopathy on neuroglobin, treated with a neuroglobin antisense nucleotide to block gene expression, or given hemin, a neuroglobin inducer. Following sepsis induction, diagnosis, and treatment, the brains were analyzed for both gross and ultrastructural morphology. Also, neuronal neuroglobin immunoreactivity and apoptosis (via terminal uridine nucleotide end-labeling) were examined. Blood serum levels were then analyzed for neuroglobin, superoxide dismutase, and malondialdehyde levels. We determined that sepsis-associated encephalopathy induces damage evident when examining both gross and ultrastructural morphology, as well as induces neuronal neuroglobin expression. Also, blockade of neuroglobin expression via antisense treatment will exacerbate these pathological effects, while increasing neuroglobin levels via hemin will ameliorate them. Blood analysis found that levels of superoxide dismutase and malondialdehyde mirrored the level of pathology found in the brain, while plasma neuroglobin levels reflected the amount of neuronal neuroglobin immunoreactivity. We conclude that neuroglobin is involved in the pathogenesis of sepsis-associated encephalopathy and has neuroprotective effects. We also determined that hemin has protective effects against sepsis-associated encephalopathy as well, most probably due to its effect on

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

Science.gov (United States)

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

2016-10-01

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

Changes in Cerebrospinal Fluid Biomarkers in Human Herpesvirus-6-Associated Acute Encephalopathy/Febrile Seizures

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Naoyuki Tanuma

2014-01-01

Full Text Available To determine the involvement of oxidative stress in the pathogenesis of acute encephalopathy associated with human herpesvirus-6 (HHV-6 infection, we measured the levels of oxidative stress markers 8-hydroxy-2′-deoxyguanosine (8-OHdG and hexanoyl-lysine adduct (HEL, tau protein, and cytokines in cerebrospinal fluid (CSF obtained from patients with HHV-6-associated acute encephalopathy (HHV-6 encephalopathy (n=16 and complex febrile seizures associated with HHV-6 (HHV-6 complex FS (n=10. We also examined changes in CSF-8OHdG and CSF-HEL levels in patients with HHV-6 encephalopathy before and after treatment with edaravone, a free radical scavenger. CSF-8-OHdG levels in HHV-6 encephalopathy and HHV-6 complex FS were significantly higher than in control subjects. In contrast, CSF-HEL levels showed no significant difference between groups. The levels of total tau protein in HHV-6 encephalopathy were significantly higher than in control subjects. In six patients with HHV-6 infection (5 encephalopathy and 1 febrile seizure, the CSF-8-OHdG levels of five patients decreased after edaravone treatment. Our results suggest that oxidative DNA damage is involved in acute encephalopathy associated with HHV-6 infection.

DECREASED BILIRUBIN TRANSPORT IN THE PERFUSED LIVER OF ENDOTOXEMIC RATS

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

1994-01-01

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

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

NARCIS (Netherlands)

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

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

Bronchiolitis-associated encephalopathy in critically-ill infants: an underestimated complication?

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Antonucci, Roberto; Chiappe, Stefano; Porcella, Annalisa; Rosatelli, Daniela; Fanos, Vassilios

2010-05-01

To investigate the bronchiolitis-associated encephalopathy in critically ill infants. The records of infants with severe bronchiolitis admitted to our intensive care unit between 1991 and 2003 were reviewed. Subjects with underlying neurological disorders were excluded. Encephalopathy was defined as occurrence of seizures or at least two nonconvulsive neurologic manifestations. A semistructured telephone interview investigated long-term neurodevelopmental outcome. Twenty-one infants (11 newborns) were enrolled. All patients required oxygen supplementation and 14 required mechanical ventilation. Encephalopathy occurred in 10 infants, six of whom developed seizures. Encephalopathic infants frequently (six of nine) showed transient EEG abnormalities, and occasionally (one of nine) cranial ultrasound abnormalities. A positive respiratory syncytial virus test was found in five of nine encephalopathic infants. One encephalopathic patient died, while 20 infants clinically normalised before discharge and showed a good neurodevelopmental outcome. Acute encephalopathy was frequently observed in our patients with severe bronchiolitis. Long-term prognosis of encephalopathic infants was good.

The mechanisms and treatment of asphyxial encephalopathy

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Guido eWassink

2014-02-01

Full Text Available Acute post-asphyxial encephalopathy occurring around the time of birth remains a major cause of death and disability. The recent seminal insight that allows active neuroprotective treatment is that even after profound asphyxia (the primary phase, many brain cells show initial recovery from the insult during a short latent phase, typically lasting approximately 6 h, only to die hours to days later after a secondary deterioration characterized by seizures, cytotoxic edema, and progressive failure of cerebral oxidative metabolism. Although many of these secondary processes are potentially injurious, they appear to be primarily epiphenomena of the ‘execution’ phase of cell death. Animal and human studies designed around this conceptual framework have shown that moderate cerebral hypothermia initiated as early as possible but before the onset of secondary deterioration, and continued for a sufficient duration to allow the secondary deterioration to resolve, has been associated with potent, long-lasting neuroprotection. Recent clinical trials show that while therapeutic hypothermia significantly reduces morbidity and mortality, many babies still die or survive with disabilities. The challenge for the future is to find ways of improving the effectiveness of treatment. In this review, we will dissect the known mechanisms of hypoxic-ischemic brain injury in relation to the known effects of hypothermic neuroprotection.

Diabetic encephalopathy: a cerebrovascular disorder?

NARCIS (Netherlands)

Manschot, S.M.

2006-01-01

Animal study: The aim was to investigate the role of vascular disturbances in the development of experimental diabetic encephalopathy. We describe the effects of treatment with the Angiotensin Converting Enzyme(ACE)-inhibitor enalapril (treatment aimed at the

Decreased bilirubin transport in the perfused liver of endotoxemic rats

NARCIS (Netherlands)

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

1994-01-01

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

SCN8A encephalopathy: Research progress and prospects.

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Meisler, Miriam H; Helman, Guy; Hammer, Michael F; Fureman, Brandy E; Gaillard, William D; Goldin, Alan L; Hirose, Shinichi; Ishii, Atsushi; Kroner, Barbara L; Lossin, Christoph; Mefford, Heather C; Parent, Jack M; Patel, Manoj; Schreiber, John; Stewart, Randall; Whittemore, Vicky; Wilcox, Karen; Wagnon, Jacy L; Pearl, Phillip L; Vanderver, Adeline; Scheffer, Ingrid E

2016-07-01

On April 21, 2015, the first SCN8A Encephalopathy Research Group convened in Washington, DC, to assess current research into clinical and pathogenic features of the disorder and prepare an agenda for future research collaborations. The group comprised clinical and basic scientists and representatives of patient advocacy groups. SCN8A encephalopathy is a rare disorder caused by de novo missense mutations of the sodium channel gene SCN8A, which encodes the neuronal sodium channel Nav 1.6. Since the initial description in 2012, approximately 140 affected individuals have been reported in publications or by SCN8A family groups. As a result, an understanding of the severe impact of SCN8A mutations is beginning to emerge. Defining a genetic epilepsy syndrome goes beyond identification of molecular etiology. Topics discussed at this meeting included (1) comparison between mutations of SCN8A and the SCN1A mutations in Dravet syndrome, (2) biophysical properties of the Nav 1.6 channel, (3) electrophysiologic effects of patient mutations on channel properties, (4) cell and animal models of SCN8A encephalopathy, (5) drug screening strategies, (6) the phenotypic spectrum of SCN8A encephalopathy, and (7) efforts to develop a bioregistry. A panel discussion of gaps in bioregistry, biobanking, and clinical outcomes data was followed by a planning session for improved integration of clinical and basic science research. Although SCN8A encephalopathy was identified only recently, there has been rapid progress in functional analysis and phenotypic classification. The focus is now shifting from identification of the underlying molecular cause to the development of strategies for drug screening and prioritized patient care. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

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

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Stoniene, Dalia; Buinauskiene, Jūrate; Markūniene, Egle

2009-01-01

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

About pathognomonic images: an infrequent case of acute encephalopathy

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Alessandro Grasso

2013-05-01

Full Text Available BACKGROUND The occurrence of acute encephalopathy is a dramatic clinical dilemma when usual diagnostic techniques (blood tests, cerebral CT and cerebrospinal fluid analysis show no abnormalities. CLINICAL CASE We describe a case of a 73 years old man admitted in our Internal Medicine Unit for acute diarrhoea with vomiting and fever who developed a prolonged gastrointestinal dysmotility syndrome with poor nutritional intake. Although a parenteral support was provided, he developed acute encephalopathy followed by hypotension and lactic acidosis without evidence of renal and hepatic disease or glycemic alterations. Likewise, no cerebral CT and cerebrospinal fluid alterations were found. Conversely, cerebral MRI showed marked and diffuse DP-2 and FLAIR hyperintensity of the mesencephalic tectal plate, of the periaqueductal area, and of the periventricular region of the third ventricle including the median thalamic area. These MRI descriptions were considered pathognomonic of Wernicke encephalopathy. Thus, the immediate use of ev thiamine was followed by a prompt and complete recovery of neurological, hemodinamic and metabolic conditions. CONCLUSIONS Non-alcoholic Wernicke encephalopathy is a rare and dramatic clinical event with high mortality. In this context, brain MRI is the best diagnostic tool providing a typical picture.

Advanced neuroimaging techniques for the term newborn with encephalopathy.

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Chau, Vann; Poskitt, Kenneth John; Miller, Steven Paul

2009-03-01

Neonatal encephalopathy is associated with a high risk of morbidity and mortality in the neonatal period and of long-term neurodevelopmental disability in survivors. Advanced magnetic resonance techniques now play a major role in the clinical care of newborns with encephalopathy and in research addressing this important condition. From conventional magnetic resonance imaging, typical patterns of injury have been defined in neonatal encephalopathy. When applied in contemporary cohorts of newborns with encephalopathy, the patterns of brain injury on magnetic resonance imaging distinguish risk factors, clinical presentation, and risk of abnormal outcome. Advanced magnetic resonance techniques such as magnetic resonance spectroscopy, diffusion-weighted imaging, and diffusion tensor imaging provide novel perspectives on neonatal brain metabolism, microstructure, and connectivity. With the application of these imaging tools, it is increasingly apparent that brain injury commonly occurs at or near the time of birth and evolves over the first weeks of life. These observations have complemented findings from trials of emerging strategies of brain protection, such as hypothermia. Application of these advanced magnetic resonance techniques may enable the earliest possible identification of newborns at risk of neurodevelopmental impairment, thereby ensuring appropriate follow-up with rehabilitation and psychoeducational resources.

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

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

2016-12-01

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

A Rare Case of Reversible Encephalopathy Syndrome Accompanying Late Postpartum Eclampsia or Hypertensive Encephalopathy-A Clinical Dilemma

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Shakuntala PN

2012-04-01

Full Text Available Posterior Reversible Encephalopathy Syndrome (PRES refers to a clinic-radiologic diagnosis. Clinically it is characterized by non specific symptoms such as headache, confusion, visual disturbances and seizures. The radiological findings in PRES are thought to be due to vasogenic oedema, predominantly in the posterior cerebral hemispheres, and are reversible with appropriate management. We report a case of reversible encephalopathy diagnosed by MRI scan occurring in atypical areas like the caudate and lentiform nuclei of the brain following an uneventful lower segment caesarean section in a normotensive patient, who was successfully treated with antihypertensives, anticonvulsants and supportive treatment. The differential diagnosis of convulsions in the post-partum period is discussed.

Hypothermia therapy for newborns with hypoxic ischemic encephalopathy.

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Silveira, Rita C; Procianoy, Renato S

2015-01-01

Therapeutic hypothermia reduces cerebral injury and improves the neurological outcome secondary to hypoxic ischemic encephalopathy in newborns. It has been indicated for asphyxiated full-term or near-term newborn infants with clinical signs of hypoxic-ischemic encephalopathy (HIE). A search was performed for articles on therapeutic hypothermia in newborns with perinatal asphyxia in PubMed; the authors chose those considered most significant. There are two therapeutic hypothermia methods: selective head cooling and total body cooling. The target body temperature is 34.5 °C for selective head cooling and 33.5 °C for total body cooling. Temperatures lower than 32 °C are less neuroprotective, and temperatures below 30 °C are very dangerous, with severe complications. Therapeutic hypothermia must start within the first 6h after birth, as studies have shown that this represents the therapeutic window for the hypoxic-ischemic event. Therapy must be maintained for 72 h, with very strict control of the newborn's body temperature. It has been shown that therapeutic hypothermia is effective in reducing neurologic impairment, especially in full-term or near-term newborns with moderate hypoxic-ischemic encephalopathy. Therapeutic hypothermia is a neuroprotective technique indicated for newborn infants with perinatal asphyxia and hypoxic-ischemic encephalopathy. Copyright © 2015 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Uremic Encephalopathy with Atypical Magnetic Resonance Features on Diffusion-Weighted Images

International Nuclear Information System (INIS)

Kang, Eu Gene; Jeon, Se Jeong; Choi, See Sung

2012-01-01

Uremic encephalopathy is a well-known disease with typical MR findings including bilateral vasogenic or cytotoxic edema at the cerebral cortex or basal ganglia. Involvement of the basal ganglia has been very rarely reported, typically occurring in uremic-diabetic patients. We recently treated a patient who had non-diabetic uremic encephalopathy with an atypical lesion distribution involving the supratentorial white matter, without cortical or basal ganglia involvement. To the best of our knowledge, this is only the second reported case of non-diabetic uremic encephalopathy with atypical MR findings.

Uremic Encephalopathy with Atypical Magnetic Resonance Features on Diffusion-Weighted Images

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Kang, Eu Gene; Jeon, Se Jeong; Choi, See Sung [Dept. of Radiology, Wonkwang University School of Medicine and Hospital, Iksan (Korea, Republic of)

2012-11-15

Uremic encephalopathy is a well-known disease with typical MR findings including bilateral vasogenic or cytotoxic edema at the cerebral cortex or basal ganglia. Involvement of the basal ganglia has been very rarely reported, typically occurring in uremic-diabetic patients. We recently treated a patient who had non-diabetic uremic encephalopathy with an atypical lesion distribution involving the supratentorial white matter, without cortical or basal ganglia involvement. To the best of our knowledge, this is only the second reported case of non-diabetic uremic encephalopathy with atypical MR findings.

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

Science.gov (United States)

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

2017-03-01

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

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

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

2016-01-01

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

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

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

2011-11-15

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

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

International Nuclear Information System (INIS)

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

2011-01-01

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

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

Science.gov (United States)

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

2014-01-01

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

EPILEPTIC ENCEPHALOPATHY WITH CONTINUOUS SPIKES-WAVES ACTIVITY DURING SLEEP

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E. D. Belousova

2012-01-01

Full Text Available The author represents the review and discussion of current scientific literature devoted to epileptic encephalopathy with continuous spikes-waves activity during sleep — the special form of partly reversible age-dependent epileptic encephalopathy, characterized by triad of symptoms: continuous prolonged epileptiform (spike-wave activity on EEG in sleep, epileptic seizures and cognitive disorders. The author describes the aspects of classification, pathogenesis and etiology, prevalence, clinical picture and diagnostics of this disorder, including the peculiar anomalies on EEG. The especial attention is given to approaches to the treatment of epileptic encephalopathy with continuous spikeswaves activity during sleep. Efficacy of valproates, corticosteroid hormones and antiepileptic drugs of other groups is considered. The author represents own experience of treatment this disorder with corticosteroids, scheme of therapy and assessment of efficacy.

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

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Honoré, B; Sato, H; Brodersen, R

1988-01-01

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

Effect of antibiotics, prebiotics and probiotics in treatment for hepatic encephalopathy.

NARCIS (Netherlands)

Bongaerts, G.P.A.; Severijnen, R.S.V.M.; Timmerman, H.

2005-01-01

In order to reduce ammonia production by urease-positive bacteria Solga recently hypothesised (S.F. Solga, Probiotics can treat hepatic encephalopathy, Medical Hypotheses 2003; 61: 307-13), that probiotics are new therapeutics for hepatic encephalopathy (HE), and that they may replace antibiotics

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

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

2014-01-01

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

Nonconvulsive Status Epilepticus in Hepatic Encephalopathy

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Hyung Kim

2011-05-01

Full Text Available We discuss a case of a 64-year-old male with a history of liver failure presenting with altered mental status, initially diagnosed with hepatic encephalopathy but ultimately diagnosed with nonconvulsive status epilepticus (NCSE by electroencephalogram (EEG. NCSE is a difficult diagnosis to make, given no clear consensus on diagnostic criteria. Especially in the intensive care unit setting of persistent altered mental status with no clear etiology, NCSE must be considered in the differential diagnosis, as the consequences of delayed diagnosis and treatment can be substantial. EEG can be useful in the evaluation of patients with hepatic encephalopathy who have persistently altered levels of consciousness despite optimal medical management. [West J Emerg Med. 2011;12(4:372–374.

Can the tyrosine kinase inhibitors trigger metabolic encephalopathy in cirrhotic patients?

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Brandi, Giovanni; de Rosa, Francesco; Calzà, Laura; Girolamo, Stefania Di; Tufoni, Manuel; Ricci, Carmen Serena; Cirignotta, Fabio; Caraceni, Paolo; Biasco, Guido

2013-03-01

Sorafenib is the standard treatment of advanced hepatocarcinoma (HCC) in cirrhotic patients with preserved liver function. It shares many adverse effects with other tyrosine-kinase (TK) inhibitors and antiangiogenic drugs. TK inhibitors could have a direct toxicity on CNS, both by interfering with TK-related pathways and by inhibiting angiogenesis. The aim of this study was to investigate whether sorafenib administration can be associated to metabolic encephalopathy in patients with cirrhosis. We retrospectively reviewed medical records of all cirrhotic patients treated with sorafenib for HCC afferent at our Department from January 2009 to December 2011. Among 62 patients, we identified 10 patients with clinically significant cognitive impairment. Seven of these were clearly diagnosed with overt hepatic encephalopathy (HE), one with brain metastases and two with drug-related toxic-metabolic encephalopathy. These last two cases were characterized by severe cognitive impairment, mood alteration and memory deficit. Clinical exam, blood tests and brain CT excluded organic causes of encephalopathy and precipitating factors of HE. Sorafenib discontinuation was associated with complete reversal of the syndrome, which recurred on drug re-administration in one case. Our study suggests that sorafenib may be a precipitating factor of metabolic encephalopathy in cirrhotic patients with advanced HCC. This neurological syndrome appears to be not responsive to the conventional treatment for HE, but it is fully reversible by drug discontinuation. It can be speculated that the potential direct neuronal action of sorafenib may represent a trigger for the onset of metabolic encephalopathy in a subset of cirrhotic patients. © 2012 John Wiley & Sons A/S.

Diffusion weighted MR imaging of acute Wernicke's encephalopathy

International Nuclear Information System (INIS)

Chung, Tae-Ick; Kim, Joong-Seok; Park, Soung-Kyeong; Kim, Beum-Saeng; Ahn, Kook-Jin; Yang, Dong-Won

2003-01-01

We report a case of Wernicke's encephalopathy in which diffusion-weighted MR images demonstrated symmetrical hyperintense lesions in the paraventricular area of the third ventricles and medial thalami. Apparent diffusion coefficient mapping showed isointensity in the aforementioned areas. Diffusion-weighted MR images may provide evidence of vasogenic edema associated with thiamine deficiency, proven in the histopathology of experimental animals. In addition, diffusion-weighted MRI has many advantages over T2 or FLARE-weighted brain MRI in detecting structural and functional abnormalities in Wernicke's encephalopathy

Oxidation reactions of bilirubin in aqueous solutions

International Nuclear Information System (INIS)

Mohan, Hari; Gopinathan, C.

1990-01-01

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

Localized Cerebral Energy Failure in DNA Polymerase Gamma-Associated Encephalopathy Syndromes

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Tzoulis, Charalampos; Neckelmann, Gesche; Mork, Sverre J.; Engelsen, Bernt E.; Viscomi, Carlo; Moen, Gunnar; Ersland, Lars; Zeviani, Massimo; Bindoff, Laurence A.

2010-01-01

Mutations in the catalytic subunit of the mitochondrial DNA-polymerase gamma cause a wide spectrum of clinical disease ranging from infantile hepato-encephalopathy to juvenile/adult-onset spinocerebellar ataxia and late onset progressive external ophthalmoplegia. Several of these syndromes are associated with an encephalopathy that…

The Thompson Encephalopathy Score and Short-Term Outcomes in Asphyxiated Newborns Treated With Therapeutic Hypothermia

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Thorsen, Patricia; Jansen-van der Weide, Martine C.; Groenendaal, Floris; Onland, Wes; van Straaten, Henrika L. M.; Zonnenberg, Inge; Vermeulen, Jeroen R.; Dijk, Peter H.; Dudink, Jeroen; Rijken, Monique; van Heijst, Arno; Dijkman, Koen P.; Cools, Filip; Zecic, Alexandra; van Kaam, Anton H.; de Haan, Timo R.

2016-01-01

The Thompson encephalopathy score is a clinical score to assess newborns suffering from perinatal asphyxia. Previous studies revealed a high sensitivity and specificity of the Thompson encephalopathy score for adverse outcomes (death or severe disability). Because the Thompson encephalopathy score

Severe posterior reversible encephalopathy in pheochromocytoma: Importance of susceptibility-weighted MRI

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Serter, Asil; Alkan, Alpay; Aralasmak, Ayse; Kocakoc, Ercan [Dept. of Radiology, Bezmialem Vakif University School of Medicine, Istanbul (Turkmenistan)

2013-10-15

Pheochromocytoma is a rare cause of hypertension in children. Hypertension is one of the common reasons of posterior reversible encephalopathy. Intracerebral hemorrhage is a serious and unexpected complication of hypertensive encephalopathy due to pheochromocytoma, and very rarely seen in the childhood. Intracerebral hemorrhages should be searched if there are hypertensive reversible signal changes on the brain. Susceptibility weighted imaging (SWI) is a more sensitive method than conventional MRI when demonstrating cerebral microhemorrhagic foci. This is the first report of SWI findings on intracerebral hemorrhages in basal ganglia, brain stem and periventricular white matter due to hypertensive encephalopathy in a child with pheochromocytoma.

Valproic Acid Induced Hyperammonaemic Encephalopathy

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Amanat, S.; Shahbaz, N.; Hassan, Y.

2013-01-01

Objective: To observe clinical and laboratory features of valproic acid-induced hyperammonaemic encephalopathy in patients taking valproic acid. Methods: Observational study was conducted at the Neurology Department, Dow University of Health Sciences, Civil Hospital, Karachi, from February 26, 2010 to March 20, 2011. Ten patients on valproic acid therapy of any age group with idiopathic or secondary epilepsy, who presented with encephalopathic symptoms, were registered and followed up during the study. Serum ammonia level, serum valproic acid level, liver function test, cerebrospinal fluid examination, electroencephalogram and brain imaging of all the patients were done. Other causes of encephalopathy were excluded after clinical and appropriate laboratory investigations. Microsoft Excel 2007 was used for statistical analysis. Results: Hyperammonaemia was found in all patients with encephalopathic symptoms. Rise in serum ammonia was independent of dose and serum level of valproic acid. Liver function was also found to be normal in 80% (n=8) of the patients. Valproic acid was withdrawn in all patients. Three (30%) patients improved only after the withdrawal of valproic acid. Six (60%) patients improved after L-Carnitine replacement, one (10%) after sodium benzoate. On followup, serum ammonia had reduced to normal in five (50%) patients and to more than half of the baseline level in two (20%) patients. Three (30%) patients were lost to followup after complete clinical improvement. Conclusion: Within therapeutic dose and serum levels, valproic acid can cause symptomatic hyperammonaemia resulting in encephalopathy. All patients taking valproic acid presenting with encephalopathic symptoms must be monitored for the condition. (author)

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

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

2016-01-01

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

Treatment of Hyponatremic Encephalopathy in the Critically Ill.

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Achinger, Steven G; Ayus, Juan Carlos

2017-10-01

Hyponatremic encephalopathy, symptomatic cerebral edema due to a low osmolar state, is a medical emergency and often encountered in the ICU setting. This article provides a critical appraisal and review of the literature on identification of high-risk patients and the treatment of this life-threatening disorder. Online search of the PubMed database and manual review of articles involving risk factors for hyponatremic encephalopathy and treatment of hyponatremic encephalopathy in critical illness. Hyponatremic encephalopathy is a frequently encountered problem in the ICU. Prompt recognition of hyponatremic encephalopathy and early treatment with hypertonic saline are critical for successful outcomes. Manifestations are varied, depending on the extent of CNS's adaptation to the hypoosmolar state. The absolute change in serum sodium alone is a poor predictor of clinical symptoms. However, certain patient specific risks factors are predictive of a poor outcome and are important to identify. Gender (premenopausal and postmenopausal females), age (prepubertal children), and the presence of hypoxia are the three main clinical risk factors and are more predictive of poor outcomes than the rate of development of hyponatremia or the absolute decrease in the serum sodium. In patients with hyponatremic encephalopathy exhibiting neurologic manifestations, a bolus of 100 mL of 3% saline, given over 10 minutes, should be promptly administered. The goal of this initial bolus is to quickly treat cerebral edema. If signs persist, the bolus should be repeated in order to achieve clinical remission. However, the total change in serum sodium should not exceed 5 mEq/L in the initial 1-2 hours and 15-20 mEq/L in the first 48 hours of treatment. It has recently been demonstrated in a prospective fashion that 500 mL of 3% saline at an infusion rate of 100 mL per hour can be given safely. It is critical to recognize the early signs of cerebral edema (nausea, vomiting, and headache

Magnetic resonance imaging in a case of Wernicke's encephalopathy

International Nuclear Information System (INIS)

Pagnan, L.; Pozzi-Mucelli, R.S.; Berlot, G.

1998-01-01

Wernicke's encephalopathy is an uncommon disorder caused by a thiamine deficiency which is clinically characterized by the triad of ophthalmoplegia, ataxia and disturbances of consciousness, each finding being variably present. The disease is caused by malnutrition or malabsorption, and is often associated with prolonged alcohol intake, neoplasm and extensive inflammatory processes of the digestive tract and parenteral hyperalimentation-induced gastrointestinal mucosal atrophy. Clinical diagnosis can be elusive and MRI may be the only imaging technique able to detect the cerebral lesions, whose type and distribution are characteristic of the Wernicke's encephalopathy, whereas CT is positive only in exceptional cases. We report a case of a 56-year-old woman who developed a Wernicke's encephalopathy 1 month after a colonic resection with signal intensity changes located in the mammillary bodies and in the medial thalamic nuclei. (orig.)

Acute Infantile Encephalopathy Predominantly Affecting The Frontal Lobes (AIEF).

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Raha, Sarbani; Udani, Vrajesh

2012-12-01

Acute Infantile Encephalopathy Predominantly Affecting the Frontal Lobes (AIEF) is a relatively recent described entity. This article includes case reports of two patients who had bifrontal involvement during acute febrile encephalopathy. Case 1 describes a 1-y-old boy who presented with hyperpyrexia and dialeptic seizures. Imaging revealed significant bilateral frontal lobe involvement while serology proved presence of Influenza B infection. Over a period of one wk, he recovered with significant cognitive decline and perseveratory behavior. Another 6-y-old boy presented with language and behavioral problems suggestive of frontal dysfunction after recovering from prolonged impairment of consciousness following a convulsive status epilepticus. Bilateral superior frontal lesions with gyral swelling was evident on neuroimaging. These cases are among the very few cases of AIEF described in recent literature and the article also reviews this unique subtype of acute encephalopathy.

Probiotics for people with hepatic encephalopathy.

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Dalal, Rohan; McGee, Richard G; Riordan, Stephen M; Webster, Angela C

2017-02-23

Hepatic encephalopathy is a disorder of brain function as a result of liver failure or portosystemic shunt or both. Both hepatic encephalopathy (clinically overt) and minimal hepatic encephalopathy (not clinically overt) significantly impair patient's quality of life and daily functioning, and represent a significant burden on healthcare resources. Probiotics are live micro-organisms, which when administered in adequate amounts, may confer a health benefit on the host. To determine the beneficial and harmful effects of probiotics in any dosage, compared with placebo or no intervention, or with any other treatment for people with any grade of acute or chronic hepatic encephalopathy. This review did not consider the primary prophylaxis of hepatic encephalopathy. We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, Science Citation Index Expanded, conference proceedings, reference lists of included trials, and the World Health Organization International Clinical Trials Registry Platform until June 2016. We included randomised clinical trials that compared probiotics in any dosage with placebo or no intervention, or with any other treatment in people with hepatic encephalopathy. We used standard methodological procedures expected by The Cochrane Collaboration. We conducted random-effects model meta-analysis due to obvious heterogeneity of participants and interventions. We defined a P value of 0.05 or less as significant. We expressed dichotomous outcomes as risk ratio (RR) and continuous outcomes as mean difference (MD) with 95% confidence intervals (CI). We included 21 trials with 1420 participants, of these, 14 were new trials. Fourteen trials compared a probiotic with placebo or no treatment, and seven trials compared a probiotic with lactulose. The trials used a variety of probiotics; the most commonly used group of probiotic was VSL#3, a proprietary name for a group of eight probiotics. Duration of administration

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

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

2018-02-01

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

Delayed encephalopathy after acute carbon monoxide poisoning

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Mehmet İbrahim Turan

2014-03-01

Full Text Available Carbon monoxide poisoning is a major cause of death following attempted suicide and accidental exposures. Although clinical presentation depends on the duration and the intensity of exposure, the assessment of the severity of intoxication is difficult. A small percentage of patients who show complete initial recovery may develop delayed neurological deficits. Delayed encephalopathy after acute carbon monoxide poisoning is a rare and poor prognosis neurologic disorders and there is no specific treatment. We present a case with early onset of delayed encephalopathy after acute carbon monoxide poisoning with typical cranial imaging findings in a child with atypical history and clinical presentation.

Correlation of hyponatremia with hepatic encephalopathy and severity of liver disease.

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Qureshi, Muhammad Omar; Khokhar, Nasir; Saleem, Atif; Niazi, Tariq Khan

2014-02-01

To assess the frequency of low serum sodium levels and to correlate it with the severity of liver disease and hepatic encephalopathy (HE) in patients coming to the tertiary care hospital. Observational study. Shifa International Hospital, Islamabad, from January 2011 to January 2012. A total of 202 patients with hepatic encephalopathy and chronic liver disease had serum sodium measured. The HE was graded according to the West Haven classification (4 grades). Relationship of hyponatremia was correlated with severity grade of encephalopathy using Spearman rank correlation test. Out of 202 patients, 62 (30.7%) patients had serum sodium less than 130 meq/l. Out of 202, HE was present in 69 (34.15%) patients and out of these, 38 had grade III-IV HE and 31 had grade I - II HE. Out of 69 patients with HE 57 had sodium less than 135 (p liver disease. The existence of serum sodium concentration encephalopathy compared with patients with serum sodium concentration > 135 mmol/L.

Brain gamma-aminobutyric acid deficiency in dialysis encephalopathy.

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Sweeney, V P; Perry, T L; Price, J D; Reeve, C E; Godolphin, W J; Kish, S J

1985-02-01

We measured levels of gamma-aminobutyric acid (GABA) in the CSF and in the autopsied brain of patients with dialysis encephalopathy. GABA concentrations were low in the CSF of three of five living patients. Mean GABA content was reduced by 30 to 50% in five brain regions (frontal, occipital, and cerebellar cortex, caudate nucleus, and medial dorsal thalamus) in five fatal cases. GABA content was normal in brain regions where GABA is characteristically reduced in Huntington's disease. Choline acetyltransferase activity was diminished (by 25 to 35%) in cerebral cortex of the dialysis encephalopathy patients.

The thalamus in cirrhotic patients with and without hepatic encephalopathy: A volumetric MRI study

International Nuclear Information System (INIS)

Tao, Ran; Zhang, Jiuquan; You, Zhonglan; Wei, Luqing; Fan, Yi; Cui, Jinguo; Wang, Jian

2013-01-01

Background and aims: The thalamus is a major relay and filter station in the central neural system. Some previous studies have suggested that the thalamus maybe implicated in the pathogenesis of hepatic encephalopathy. The aim of our study was to investigate changing thalamic volumes in cirrhotic patients with and without hepatic encephalopathy. Methods: Neuropsychological tests and structural MR scanning were performed on 24 cirrhotic patients, 23 cirrhotic patients with minimal hepatic encephalopathy, 24 cirrhotic patients during their first episode of overt hepatic encephalopathy, and 33 healthy controls. Voxel-based morphometry analysis was performed to detect gray matter morphological changes. The thalamus and whole brain volume were extrapolated. A receiver operating characteristic curve analysis of thalamic volumes was used to discriminate patients with minimal hepatic encephalopathy from those with hepatic cirrhosis. Results: Thalamic volume increased in a stepwise manner in patients with progressively worse stages of hepatic encephalopathy compared to healthy subjects. Additionally, a comparison of gray matter morphometry between patients with Child–Pugh grades A, B, or C and controls revealed a progression in thalamic volumes in parallel with the degree of liver failure. Moreover, thalamic volume was significantly correlated with the number connection test A time and digit-symbol test score in cirrhotic patients with minimal hepatic encephalopathy (r = 0.659, P = 0.001; r = −0.577, P = 0.004; respectively). The area under the receiver operating characteristic curve was 0.827 (P = 0.001). Conclusions: A significantly increased thalamic volume may be provide an objective imaging measure for predicting seizures due to minimal hepatic encephalopathy in cirrhotic patients

The thalamus in cirrhotic patients with and without hepatic encephalopathy: A volumetric MRI study

Energy Technology Data Exchange (ETDEWEB)

Tao, Ran, E-mail: taoran1648@yahoo.cn [Department of Radiology, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China); Department of Radiology, Bethune International Peace Hospital of People' s Liberty Army, Shijiazhuang 050082, Hebei Province (China); Zhang, Jiuquan, E-mail: jiuquanzhang@yahoo.com [Department of Radiology, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China); You, Zhonglan, E-mail: you_zhonglan@163.com [Department of Infectious Diseases, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China); Wei, Luqing, E-mail: weiluqing@foxmail.com [Department of Radiology, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China); Fan, Yi, E-mail: fanyi1978@yahoo.cn [Department of Infectious Diseases, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China); Cui, Jinguo, E-mail: cuijinguo2005@163.com [Department of Radiology, Bethune International Peace Hospital of People' s Liberty Army, Shijiazhuang 050082, Hebei Province (China); Wang, Jian, E-mail: wangjian_811@yahoo.com [Department of Radiology, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China)

2013-11-01

Background and aims: The thalamus is a major relay and filter station in the central neural system. Some previous studies have suggested that the thalamus maybe implicated in the pathogenesis of hepatic encephalopathy. The aim of our study was to investigate changing thalamic volumes in cirrhotic patients with and without hepatic encephalopathy. Methods: Neuropsychological tests and structural MR scanning were performed on 24 cirrhotic patients, 23 cirrhotic patients with minimal hepatic encephalopathy, 24 cirrhotic patients during their first episode of overt hepatic encephalopathy, and 33 healthy controls. Voxel-based morphometry analysis was performed to detect gray matter morphological changes. The thalamus and whole brain volume were extrapolated. A receiver operating characteristic curve analysis of thalamic volumes was used to discriminate patients with minimal hepatic encephalopathy from those with hepatic cirrhosis. Results: Thalamic volume increased in a stepwise manner in patients with progressively worse stages of hepatic encephalopathy compared to healthy subjects. Additionally, a comparison of gray matter morphometry between patients with Child–Pugh grades A, B, or C and controls revealed a progression in thalamic volumes in parallel with the degree of liver failure. Moreover, thalamic volume was significantly correlated with the number connection test A time and digit-symbol test score in cirrhotic patients with minimal hepatic encephalopathy (r = 0.659, P = 0.001; r = −0.577, P = 0.004; respectively). The area under the receiver operating characteristic curve was 0.827 (P = 0.001). Conclusions: A significantly increased thalamic volume may be provide an objective imaging measure for predicting seizures due to minimal hepatic encephalopathy in cirrhotic patients.

Hypothyroidism-induced Reversible Encephalopathy as a Cause of Aggravation of Parkinsonism and Myoclonus in Parkinson's Disease.

Science.gov (United States)

Ehm, Gwanhee; Kim, Han-Joon; Jeon, Beomseok

2017-01-01

Myoclonus and encephalopathy are unusual in patients with Parkinson's disease (PD). We describe the case of a 59-year-old male with PD who developed myoclonus and encephalopathy. Underlying hypothyroidism was revealed after admission and treated with levothyroxine. Myoclonus and encephalopathy were completely resolved following thyroid hormone replacement. Hypothyroidism can cause reversible myoclonus and encephalopathy along with unusual aggravation of parkinsonism symptoms in patients with PD.

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

Science.gov (United States)

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

2016-10-01

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

Bilirubin levels determine vascular complications in diabetes mellitus type 2

Directory of Open Access Journals (Sweden)

Yu V Pankratova

2013-03-01

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

Early Recognition of Chronic Traumatic Encephalopathy Through FDDNP PET Imaging

Science.gov (United States)

2017-10-01

characteristic distribution is felt to be the cardinal pathologic feature of Chronic Traumatic Encephalopathy. This project will examine whether FDDNP PET...chronic traumatic encephalopathy (CTE). Pathological series have indicated that a characteristic feature of CTE is accumulation of tau protein in the...3. Accomplishments: Major goals: Upon receiving approval from the Human Research Protection Office, enrollment of participants began in March , 2015