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Sample records for bilirubin exposure impairs

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

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    Filipa L Cardoso

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

  2. Apoptosis and impairment of neurite network by short exposure of immature rat cortical neurons to unconjugated bilirubin increase with cell differentiation and are additionally enhanced by an inflammatory stimulus.

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    Falcão, Ana S; Silva, Rui F M; Pancadas, Sérgio; Fernandes, Adelaide; Brito, Maria A; Brites, Dora

    2007-05-01

    Nerve cell injury induced by unconjugated bilirubin (UCB) has been implicated in brain damage during severe neonatal hyperbilirubinemia, although the molecular mechanisms underlying UCB neurotoxicity are still not clarified. It has been suggested recently that there is an association between hyperbilirubinemia and long-term neurologic dysfunctions. We incubated immature neurons with UCB to evaluate the short- and long-term effects of UCB on apoptotic death and on neuritic outgrowth and ramification. We also evaluated whether mature neurons, exposed previously to UCB in an early stage of differentiation, are more sensitive to apoptosis or to neuritic breakdown when treated with inflammatory agents, such as lipopolysaccharide and tumor necrosis factor-alpha. Results show that exposure of immature neurons to UCB increased apoptosis and provoked a reduction of both neurite extension and number of nodes. These injurious effects observed in immature cells treated with UCB were increasingly perpetuated along cell differentiation, as compared to neurons incubated in the absence of UCB. In addition, neurons that were exposed to UCB when immature showed an increased susceptibility to death by apoptosis, as well as an additional decrease in neurite outgrowth when incubated with an inflammatory agent afterward. This work shows, for the first time, that UCB induces neurite changes consistent with neurodevelopment abnormalities. Furthermore, pre-exposure to UCB followed by an inflammatory stimulus leads to an enhanced susceptibility to long-term apoptosis, as well as a greater neuritic breakdown. These data support the association between neonatal hyperbilirubinemia and the later development of mental illness, such as schizophrenia.

  3. Bilirubin - urine

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    Conjugated bilirubin - urine; Direct bilirubin - urine ... Bilirubin is not normally found in the urine. ... Increased levels of bilirubin in the urine may be due to: Biliary tract disease Cirrhosis Gallstones in the biliary tract Hepatitis Liver disease ...

  4. Bilirubin Test

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    ... than females. African Americans routinely show lower bilirubin concentrations than non-African Americans. Strenuous exercise may increase bilirubin levels. Drugs that can decrease total bilirubin include barbiturates, caffeine, penicillin, and high doses of salicylates. The drug ...

  5. Bilirubin-induced neural impairment: a special focus on myelination, age-related windows of susceptibility and associated co-morbidities.

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    Brites, Dora; Fernandes, Adelaide

    2015-02-01

    Bilirubin-induced neurologic dysfunction (BIND) and classical kernicterus are clinical manifestations of moderate to severe hyperbilirubinemia whenever bilirubin levels exceed the capacity of the brain defensive mechanisms in preventing its entrance and cytotoxicity. In such circumstances and depending on the associated co-morbidities, bilirubin accumulation may lead to short- or long-term neurodevelopmental disabilities, which may include deficits in auditory, cognitive, and motor processing. Neuronal cell death, astrocytic reactivity, and microglia activation are part of the bilirubin-induced pathogenesis. Less understood is how abnormal growth and maturation of oligodendrocytes may impact on brain development, affecting the formation of myelin tracts. Based on in-vitro and in-vivo models, as well as in clinical cases presented here, we propose the existence of impaired myelination by bilirubin with long-term sequelae, mainly in pre-term infants. Sensitive time-windows are highlighted and centered on the different developmental-dependent impairments determined by bilirubin, and the influence of sepsis and hypoxia is reviewed.

  6. Bilirubin measurements in neonates

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    Newman, Gregory J.

    2000-04-01

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

  7. Blood Test: Bilirubin

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    ... Your 1- to 2-Year-Old Blood Test: Bilirubin KidsHealth > For Parents > Blood Test: Bilirubin A A A What's in this article? What ... Análisis de sangre: bilirrubina What It Is A bilirubin test measures the level of bilirubin (a byproduct ...

  8. Modeling Impaired Hippocampal Neurogenesis after Radiation Exposure.

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    Cacao, Eliedonna; Cucinotta, Francis A

    2016-03-01

    Radiation impairment of neurogenesis in the hippocampal dentate gyrus is one of several factors associated with cognitive detriments after treatment of brain cancers in children and adults with radiation therapy. Mouse models have been used to study radiation-induced changes in neurogenesis, however the models are limited in the number of doses, dose fractions, age and time after exposure conditions that have been studied. The purpose of this study is to develop a novel predictive mathematical model of radiation-induced changes to neurogenesis using a system of nonlinear ordinary differential equations (ODEs) to represent the time, age and dose-dependent changes to several cell populations participating in neurogenesis as reported in mouse experiments exposed to low-LET radiation. We considered four compartments to model hippocampal neurogenesis and, consequently, the effects of radiation treatment in altering neurogenesis: (1) neural stem cells (NSCs), (2) neuronal progenitor cells or neuroblasts (NB), (3) immature neurons (ImN) and (4) glioblasts (GB). Because neurogenesis is decreasing with increasing mouse age, a description of the age-related dynamics of hippocampal neurogenesis is considered in the model, which is shown to be an important factor in comparisons to experimental data. A key feature of the model is the description of negative feedback regulation on early and late neuronal proliferation after radiation exposure. The model is augmented with parametric descriptions of the dose and time after irradiation dependences of activation of microglial cells and a possible shift of NSC proliferation from neurogenesis to gliogenesis reported at higher doses (∼10 Gy). Predictions for dose-fractionation regimes and for different mouse ages, and prospects for future work are then discussed.

  9. 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…

  10. Biology of Bilirubin Photoisomers.

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    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.

  11. Bilirubin oxidation in brain.

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    Hansen, T W

    2000-01-01

    Bilirubin is a product of heme catabolism which by virtue of its lipid solubility can cross the blood-brain barrier and enter the brain. Neonatal jaundice is a common transitional phenomenon which is due to the combination of increased heme catabolism and rate limitations as far as hepatic conjugation and biliary excretion of bilirubin. In the great majority of cases this is an innocuous condition, which is even posited to have some beneficial effects due to the ability of bilirubin to quench free oxygen radicals. However, because bilirubin is neurotoxic, hyperbilirubinemia in the newborn may exceptionally result in death in the neonatal period, or survival with severe neurological sequelae (kernicterus). Bilirubin enters the brain through an intact blood-brain barrier. Clearance of bilirubin from brain partly involves retro-transfer through the blood-brain barrier, and possibly also through the brain-CSF barrier into CSF. Work in our lab during the past 5 years has substantiated earlier work which had suggested that bilirubin may also be metabolized in brain. The responsible enzyme is found on the inner mitochondrial membrane, and oxidizes bilirubin at a rate of 100-300 pmol bilirubin/mg protein/minute. The enzyme activity is lower in the newborn compared with the mature animal, and is also lower in neurons compared with glia. Studies of different rat strains have documented genetic variability. The enzyme is cytochrome-c-dependent, but has as yet not been unequivocally identified. The rate of oxidation of bilirubin is such that this enzyme probably contributes meaningfully to the clearance of bilirubin from brain.

  12. Neonicotinoid pesticide exposure impairs crop pollination services provided by bumblebees

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    Stanley, Dara A.; Garratt, Michael P. D.; Wickens, Jennifer B.; Wickens, Victoria J.; Potts, Simon G.; Raine, Nigel E.

    2015-12-01

    Recent concern over global pollinator declines has led to considerable research on the effects of pesticides on bees. Although pesticides are typically not encountered at lethal levels in the field, there is growing evidence indicating that exposure to field-realistic levels can have sublethal effects on bees, affecting their foraging behaviour, homing ability and reproductive success. Bees are essential for the pollination of a wide variety of crops and the majority of wild flowering plants, but until now research on pesticide effects has been limited to direct effects on bees themselves and not on the pollination services they provide. Here we show the first evidence to our knowledge that pesticide exposure can reduce the pollination services bumblebees deliver to apples, a crop of global economic importance. Bumblebee colonies exposed to a neonicotinoid pesticide provided lower visitation rates to apple trees and collected pollen less often. Most importantly, these pesticide-exposed colonies produced apples containing fewer seeds, demonstrating a reduced delivery of pollination services. Our results also indicate that reduced pollination service delivery is not due to pesticide-induced changes in individual bee behaviour, but most likely due to effects at the colony level. These findings show that pesticide exposure can impair the ability of bees to provide pollination services, with important implications for both the sustained delivery of stable crop yields and the functioning of natural ecosystems.

  13. Early exposure to traumatic stressors impairs emotional brain circuitry.

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    Mayuresh S Korgaonkar

    Full Text Available Exposure to early life trauma (ELT is known to have a profound impact on mental development, leading to a higher risk for depression and anxiety. Our aim was to use multiple structural imaging methods to systematically investigate how traumatic stressors early in life impact the emotional brain circuits, typically found impaired with clinical diagnosis of depression and anxiety, across the lifespan in an otherwise healthy cohort. MRI data and self-reported histories of ELT from 352 healthy individuals screened for no psychiatric disorders were analyzed in this study. The volume and cortical thickness of the limbic and cingulate regions were assessed for all participants. A large subset of the cohort also had diffusion tensor imaging data, which was used to quantify white matter structural integrity of these regions. We found a significantly smaller amygdala volume and cortical thickness in the rostral anterior cingulate cortex associated with higher ELT exposure only for the adolescence group. White matter integrity of these regions was not affected. These findings demonstrate that exposure to early life trauma is associated with alterations in the gray matter of cingulate-limbic regions during adolescence in an otherwise healthy sample. These findings are interesting in the context that the affected regions are central neuroanatomical components in the psychopathology of depression, and adolescence is a peak period for risk and onset of the disorder.

  14. Hypervulnerability to Sound Exposure through Impaired Adaptive Proliferation of Peroxisomes.

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    Delmaghani, Sedigheh; Defourny, Jean; Aghaie, Asadollah; Beurg, Maryline; Dulon, Didier; Thelen, Nicolas; Perfettini, Isabelle; Zelles, Tibor; Aller, Mate; Meyer, Anaïs; Emptoz, Alice; Giraudet, Fabrice; Leibovici, Michel; Dartevelle, Sylvie; Soubigou, Guillaume; Thiry, Marc; Vizi, E Sylvester; Safieddine, Saaid; Hardelin, Jean-Pierre; Avan, Paul; Petit, Christine

    2015-11-05

    A deficiency in pejvakin, a protein of unknown function, causes a strikingly heterogeneous form of human deafness. Pejvakin-deficient (Pjvk(-/-)) mice also exhibit variable auditory phenotypes. Correlation between their hearing thresholds and the number of pups per cage suggest a possible harmful effect of pup vocalizations. Direct sound or electrical stimulation show that the cochlear sensory hair cells and auditory pathway neurons of Pjvk(-/-) mice and patients are exceptionally vulnerable to sound. Subcellular analysis revealed that pejvakin is associated with peroxisomes and required for their oxidative-stress-induced proliferation. Pjvk(-/-) cochleas display features of marked oxidative stress and impaired antioxidant defenses, and peroxisomes in Pjvk(-/-) hair cells show structural abnormalities after the onset of hearing. Noise exposure rapidly upregulates Pjvk cochlear transcription in wild-type mice and triggers peroxisome proliferation in hair cells and primary auditory neurons. Our results reveal that the antioxidant activity of peroxisomes protects the auditory system against noise-induced damage.

  15. Postnatal arsenic exposure and attention impairment in school children.

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    Rodríguez-Barranco, Miguel; Gil, Fernando; Hernández, Antonio F; Alguacil, Juan; Lorca, Andres; Mendoza, Ramón; Gómez, Inmaculada; Molina-Villalba, Isabel; González-Alzaga, Beatriz; Aguilar-Garduño, Clemente; Rohlman, Diane S; Lacasaña, Marina

    2016-01-01

    Over the last few decades there has been an increased concern about the health risks from exposure to metallic trace elements, including arsenic, because of their potential neurotoxic effects on the developing brain. This study assessed whether urinary arsenic (UA) levels are associated with attention performance and Attention-Deficit/Hyperactivity Disorder (ADHD) in children living in an area with high industrial and mining activities in Southwestern Spain. A cross-sectional study was conducted on 261 children aged 6-9 years. Arsenic levels were determined in urine samples. Attention was measured by using 4 independent tools: a) tests from the Behavioral Assessment and Research System (BARS) designed to measure attention function: Simple Reaction Time Test (RTT), Continuous Performance Test (CPT) and Selective Attention Test (SAT); b) AULA Test, a virtual reality (VR)-based test that evaluates children's response to several stimuli in an environment simulating a classroom; c) Child Behavior Checklist (CBCL), administered to parents; and d) Teacher's Report Form (TRF), administered to teachers. Multivariate linear and logistic regression models, adjusted for potential confounders, were used to estimate the magnitude of the association between UA levels and attention performance scores. Higher UA levels were associated with an increased latency of response in RTT (β = 12.3; 95% confidence interval (CI): 3.5-21.1) and SAT (β = 3.6; 95% CI: .4-6.8) as well as with worse performance on selective and focalized attention in the AULA test (β for impulsivity = .6; 95% CI: .1-1.1; β for inattention = .5; 95% CI: .03-1.0). A dose-response relationship was observed between UA levels and inattention and impulsivity scores. In contrast, results from the CBCL and TRF tests failed to show a significant association with UA levels. In conclusion, UA levels were associated with impaired attention/cognitive function, even at levels considered safe. These results provide

  16. Embryonic alcohol exposure impairs associative learning performance in adult zebrafish.

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    Fernandes, Yohaan; Tran, Steven; Abraham, Emil; Gerlai, Robert

    2014-05-15

    The zebrafish has been proposed for modeling fetal alcohol spectrum disorders (FASD). Previous FASD research with zebrafish employed high concentrations of alcohol and/or long exposure periods. Here, we exposed zebrafish eggs to low doses of alcohol (0, 0.25, 0.50, 0.75 and 1.0% (vol/vol); external bath application of which 1/20th may reach the inside of the egg) at 16-h post-fertilization (hpf) and only for a short duration (2h) in the hope to avoid gross morphological aberrations and to mimic the more frequent FASD exposure levels. Upon reaching adulthood the exposed and control zebrafish were tested for their associative learning performance in a plus-maze. Embryonic alcohol exposure led to no gross anatomical abnormalities and did not increase mortality. Unexposed (control) zebrafish showed excellent acquisition of association between a conditioned visual stimulus (CS) and food reward, demonstrated by their preference for the target zone of the maze that contained the CS during a probe trial in the absence of reward. However, alcohol-exposed fish showed no such preference and performed indistinguishable from random chance. Locomotor activity during training and the probe trial or the amount of food consumed during training did not differ between the embryonic alcohol exposed and unexposed (control) fish, suggesting that the impaired learning performance found was unlikely to be caused by altered motivation or motor function. Our results suggest that even very small amounts of alcohol reaching the embryo for only a short duration of time may have long lasting deleterious effects on cognitive function in vertebrates.

  17. Israeli adolescents with ongoing exposure to terrorism: suicidal ideation, posttraumatic stress disorder, and functional impairment.

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    Chemtob, Claude M; Pat-Horenczyk, Ruth; Madan, Anita; Pitman, Seth R; Wang, Yanping; Doppelt, Osnat; Burns, Kelly Dugan; Abramovitz, Robert; Brom, Daniel

    2011-12-01

    In this study, we examined the relationships among terrorism exposure, functional impairment, suicidal ideation, and probable partial or full posttraumatic stress disorder (PTSD) from exposure to terrorism in adolescents continuously exposed to this threat in Israel. A convenience sample of 2,094 students, aged 12 to 18, was drawn from 10 Israeli secondary schools. In terms of demographic factors, older age was associated with increased risk for suicidal ideation, OR = 1.33, 95% CI [1.09, 1.62], p terrorism was associated with increased risk for each of the measured outcomes including probable partial or full PTSD, functional impairment, and suicidal ideation. When age, gender, level of exposure to terrorism, probable partial or full PTSD, and functional impairment were examined together, only terrorism exposure and functional impairment were associated with suicidal ideation. This study underscores the importance and feasibility of examining exposure to terrorism and functional impairment as risk factors for suicidal ideation.

  18. The clinical syndrome of bilirubin-induced neurologic dysfunction.

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    Bhutani, Vinod K; Johnson-Hamerman, Lois

    2015-02-01

    Clinicians have hypothesized a spectrum of minor neurologic manifestations, consistent with neuroanatomical reports and collectively termed as a "syndrome of bilirubin-induced neurologic dysfunction (BIND)," which can occur in the absence of classical kernicterus. The current review builds on these initial reports with a focus on clinical signs and symptoms that are assessed by standardized tools and manifest from neonatal age to childhood. These clinical manifestations are characterized by the following domains: (i) neuromotor signs; (ii) muscle tone abnormalities; (iii) hyperexcitable neonatal reflexes; (iv) variety of neurobehavior manifestations; (v) speech and language abnormalities; and (vi) evolving array of central processing abnormalities, such as sensorineural audiology and visuomotor dysfunctions. Concerns remain that the most vulnerable infants are likely to acquire BIND, either because their exposure to bilirubin is not identified as severe enough to need treatment or is prolonged but slightly below current threshold levels for intervention. Knowing that a total serum/plasma bilirubin (TB) level is not the most precise indicator of neurotoxicity, the role of expanded biomarkers or a "bilirubin panel" has yet to be validated in prospective studies. Future studies that correlate early "toxic" bilirubin exposure to long-term academic potential of children are needed to explore new insights into bilirubin's effect on the structural and functional maturation of an infant's neural network topology.

  19. 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) level

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

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    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%.

  1. The Biological Effects of Bilirubin Photoisomers.

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

    2016-01-01

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

  2. Exposure to lipophilic chemicals as a cause of neurological impairments, neurodevelopmental disorders and neurodegenerative diseases

    OpenAIRE

    Zeliger, Harold I.

    2013-01-01

    Many studies have associated environmental exposure to chemicals with neurological impairments (NIs) including neuropathies, cognitive, motor and sensory impairments; neurodevelopmental disorders (NDDs) including autism and attention deficit hyperactivity disorder (ADHD); neurodegenerative diseases (NDGs) including Alzheimer′s disease, Parkinson's disease and amyotrophic lateral sclerosis (ALS). The environmental chemicals shown to induce all these diseases include persistent organic pollutan...

  3. Quantitative imaging of bilirubin by photoacoustic microscopy

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    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.

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

    Science.gov (United States)

    Hulzebos, Christian V; Dijk, Peter H

    2014-11-01

    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) levels, or bilirubin/albumin (B/A) ratios for that matter, are more closely associated with bilirubin neurotoxicity. In this article, we review bilirubin-albumin binding, UCBfree levels, and B/A ratios in addition to TSB levels to individualize and optimize treatment especially in preterm infants. Methods to measure bilirubin-albumin binding or UCBfree are neither routinely performed in Western clinical laboratories nor incorporated in current management guidelines on unconjugated hyperbilirubinemia. For bilirubin-albumin binding, this seems justified because several of these methods have been challenged, and sufficiently powered prospective trials on the clinical benefits are lacking. Technological advances in the measurement of UCBfree may provide a convenient means for integrating UCBfree measurements into routine clinical management of jaundiced infants. A point-of-care method, as well as determination of UCBfree levels in various newborn populations, is desirable to learn more about variations in time and how various clinical pathophysiological conditions affect UCBfree levels. This will improve the estimation of approximate UCBfree levels associated with neurotoxicity. To delineate the role of UCBfree in the management of jaundiced (preterm) infants, trials are needed using UCBfree as treatment parameter. The additional use of the B/A ratio in jaundiced preterms has been evaluated in the Bilirubin Albumin Ratio Trial (BARTrial; Clinical Trials: ISRCTN74465643) but failed to demonstrate better neurodevelopmental outcome in preterm infants bilirubin toxicity. Yet, different methodologies for estimating these parameters exist, and sufficiently powered, prospective clinical

  5. 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.

  6. Mild MPP(+) exposure impairs autophagic degradation through a novel lysosomal acidity-independent mechanism.

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    Miyara, Masatsugu; Kotake, Yaichiro; Tokunaga, Wataru; Sanoh, Seigo; Ohta, Shigeru

    2016-10-01

    Parkinson's disease (PD) is the second most common neurodegenerative disorder, but its underlying cause remains unknown. Although recent studies using PD-related neurotoxin MPP(+) suggest autophagy involvement in the pathogenesis of PD, the effect of MPP(+) on autophagic processes under mild exposure, which mimics the slow progressive nature of PD, remains largely unclear. We examined the effect of mild MPP(+) exposure (10 and 200 μM for 48 h), which induces a more slowly developing cell death, on autophagic processes and the mechanistic differences with acute MPP(+) toxicity (2.5 and 5 mM for 24 h). In SH-SY5Y cells, mild MPP(+) exposure predominantly inhibited autophagosome degradation, whereas acute MPP(+) exposure inhibited both autophagosome degradation and basal autophagy. Mild MPP(+) exposure reduced lysosomal hydrolase cathepsin D activity without changing lysosomal acidity, whereas acute exposure decreased lysosomal density. Lysosome biogenesis enhancers trehalose and rapamycin partially alleviated mild MPP(+) exposure induced impaired autophagosome degradation and cell death, but did not prevent the pathogenic response to acute MPP(+) exposure, suggesting irreversible lysosomal damage. We demonstrated impaired autophagic degradation by MPP(+) exposure and mechanistic differences between mild and acute MPP(+) toxicities. Mild MPP(+) toxicity impaired autophagosome degradation through novel lysosomal acidity-independent mechanisms. Sustained mild lysosomal damage may contribute to PD. We examined the effects of MPP(+) on autophagic processes under mild exposure, which mimics the slow progressive nature of Parkinson's disease, in SH-SY5Y cells. This study demonstrated impaired autophagic degradation through a reduction in lysosomal cathepsin D activity without altering lysosomal acidity by mild MPP(+) exposure. Mechanistic differences between acute and mild MPP(+) toxicity were also observed. Sustained mild damage of lysosome may be an underlying cause

  7. Impaired Lung Mitochondrial Respiration Following Perinatal Nicotine Exposure in Rats.

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    Cannon, Daniel T; Liu, Jie; Sakurai, Reiko; Rossiter, Harry B; Rehan, Virender K

    2016-04-01

    Perinatal smoke/nicotine exposure predisposes to chronic lung disease and morbidity. Mitochondrial abnormalities may contribute as the PPARγ pathway is involved in structural and functional airway deficits after perinatal nicotine exposure. We hypothesized perinatal nicotine exposure results in lung mitochondrial dysfunction that can be rescued by rosiglitazone (RGZ; PPARγ receptor agonist). Sprague-Dawley dams received placebo (CON), nicotine (NIC, 1 mg kg(-1)), or NIC + RGZ (3 mg kg(-1)) daily from embryonic day 6 to postnatal day 21. Parenchymal lung (~10 mg) was taken from adult male offspring for mitochondrial assessment in situ. ADP-stimulated O2 consumption was less in NIC and NIC + RGZ compared to CON (F[2,14] = 17.8; 4.5 ± 0.8 and 4.1 ± 1.4 vs. 8.8 ± 2.5 pmol s mg(-1); p NIC and remediated in NIC + RGZ (F[2,14] = 3.8; p < 0.05). Reduced mitochondrial oxidative capacity and abnormal coupling were evident after perinatal nicotine exposure. RGZ improved mitochondrial function through tighter coupling of oxidative phosphorylation.

  8. Motoric impairment following manganese exposure in asteroid echinoderms.

    Science.gov (United States)

    Sköld, Helen Nilsson; Baden, Susanne P; Looström, Jakob; Eriksson, Susanne P; Hernroth, Bodil E

    2015-10-01

    In the oceans, naturally occurring manganese (Mn) is released from the sediments during events of hypoxia. While neuro- and immuno-toxic effects of bioavailable manganese are well documented for crustaceans, studies of similar effects of manganese on other marine invertebrates are comparatively few. Here, we developed a new functional test "the repeated turning assay" to investigate if manganese exposure at ∼12 mg L(-1) affected motoric behaviour of two asteroid echinoderms, the Common sea star, Asterias rubens, and the Black brittle star, Ophiocomina nigra. By measuring of the turning-over capacity, from dorsal to ventral position, after one and two weeks of manganese exposure, we showed that for both species Mn exposure significantly delayed the ability to turn. After a recovery period of two weeks, the capacity of turning-over was not restored to that of unexposed animals neither for A. rubens nor for O. nigra. Further investigation of sea stars showed that Mn accumulated ∼5 fold in the tube feet, organs involved in their turning-over activity, and the high concentration remained after the recovery period. In the tube feet we also recorded an increased activity of acetylcholinesterase (AChE), here used as a proxy for neuromuscular disturbances. The results indicated that Mn induces neuromuscular disturbance in echinoderms which is important news, given that previous studies have concluded that adult echinoderms are relatively tolerant to Mn.

  9. Does acute exposure to aldehydes impair pulmonary function and structure?

    Science.gov (United States)

    Abreu, Mariana de; Neto, Alcendino Cândido; Carvalho, Giovanna; Casquillo, Natalia Vasconcelos; Carvalho, Niedja; Okuro, Renata; Ribeiro, Gabriel C Motta; Machado, Mariana; Cardozo, Aléxia; Silva, Aline Santos E; Barboza, Thiago; Vasconcellos, Luiz Ricardo; Rodrigues, Danielle Araujo; Camilo, Luciana; Carneiro, Leticia de A M; Jandre, Frederico; Pino, Alexandre V; Giannella-Neto, Antonio; Zin, Walter A; Corrêa, Leonardo Holanda Travassos; Souza, Marcio Nogueira de; Carvalho, Alysson R

    2016-07-15

    Mixtures of anhydrous ethyl alcohol and gasoline substituted for pure gasoline as a fuel in many Brazilian vehicles. Consequently, the concentrations of volatile organic compounds (VOCs) such as ketones, other organic compounds, and particularly aldehydes increased in many Brazilian cities. The current study aims to investigate whether formaldehyde, acetaldehyde, or mixtures of both impair lung function, morphology, inflammatory and redox responses at environmentally relevant concentrations. For such purpose, C57BL/6 mice were exposed to either medical compressed air or to 4 different mixtures of formaldehyde and acetaldehyde. Eight hours later animals were anesthetized, paralyzed and lung mechanics and morphology, inflammatory cells and IL-1β, KC, TNF-α, IL-6, CCL2, MCP-1 contents, superoxide dismutase and catalalase activities were determined. The extra pulmonary respiratory tract was also analyzed. No differences could be detected between any exposed and control groups. In conclusion, no morpho-functional alterations were detected in exposed mice in relation to the control group.

  10. The Biological Effects of Bilirubin Photoisomers.

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    Jana Jasprova

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

  11. Artificial gravity exposure impairs exercise-related neurophysiological benefits.

    Science.gov (United States)

    Vogt, Tobias; Abeln, Vera; Strüder, Heiko K; Schneider, Stefan

    2014-01-17

    Artificial gravity (AG) exposure is suggested to counteract health deconditioning, theoretically complementing exercise during space habitations. Exercise-benefits on mental health are well documented (i.e. well-being, enhanced executive functions). Although AG is coherent for the integrity of fundamental physiological systems, the effects of its exposure on neurophysiological processes related to cognitive performance are poorly understood and therefore characterize the primary aim of this study. 16 healthy males participated in two randomly assigned sessions, AG and exercise (30minute each). Participants were exposed to AG at continuous +2Gz in a short-arm human centrifuge and performed moderate exercise (cycling ergometer). Using 64 active electrodes, resting EEG was recorded before (pre), immediately after (post), and 15min after (post15) each session. Alpha (7.5-12.5Hz) and beta frequencies (12.5-35.0Hz) were exported for analysis. Cognitive performance and mood states were assessed before and after each session. Cognitive performance improved after exercise (pexercise, however not after AG. Frontal alpha (post pexercise. Relaxed cortical states were indicated after exercise, but were less apparent after AG. Changes in mood states failed significance after both sessions. Summarized, the benefits to mental health, recorded after exercise, were absent after AG, indicating that AG might cause neurocognitive deconditioning.

  12. Behavioral Flexibility and Response Selection Are Impaired after Limited Exposure to Oxycodone

    Science.gov (United States)

    Seip-Cammack, Katharine M.; Shapiro, Matthew L.

    2014-01-01

    Behavioral flexibility allows individuals to adapt to situations in which rewards and goals change. Potentially addictive drugs may impair flexible decision-making by altering brain mechanisms that compute reward expectancies, thereby facilitating maladaptive drug use. To investigate this hypothesis, we tested the effects of oxycodone exposure on…

  13. Degree of Exposure to Domestic Violence, Psychopathology, and Functional Impairment in Children and Adolescents

    Science.gov (United States)

    Fernandez, Eduard Bayarri; Ezpeleta, Lourdes; Granero, Roser; de la Osa, Nuria; Domenech, Josep Maria

    2011-01-01

    There are discrepancies about whether children who witness and suffer domestic violence (DV) have similar outcomes in terms of psychopathology. This work examines the relationship between different types of exposure to DV and child psychopathology and functional impairment. One hundred and forty-four Spanish children aged from 4 to 17 years and…

  14. 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.

  15. JP-8 jet fuel can promote auditory impairment resulting from subsequent noise exposure in rats.

    Science.gov (United States)

    Fechter, Laurence D; Gearhart, Caroline; Fulton, Sherry; Campbell, Jerry; Fisher, Jeffrey; Na, Kwangsam; Cocker, David; Nelson-Miller, Alisa; Moon, Patrick; Pouyatos, Benoit

    2007-08-01

    We report on the transient and persistent effects of JP-8 jet fuel exposure on auditory function in rats. JP-8 has become the standard jet fuel utilized in the United States and North Atlantic Treaty Organization countries for military use and it is closely related to Jet A fuel, which is used in U.S. domestic aviation. Rats received JP-8 fuel (1000 mg/m(3)) by nose-only inhalation for 4 h and half of them were immediately subjected to an octave band of noise ranging between 97 and 105 dB in different experiments. The noise by itself produces a small, but permanent auditory impairment. The current permissible exposure level for JP-8 is 350 mg/m(3). Additionally, a positive control group received only noise exposure, and a fourth group consisted of untreated control subjects. Exposures occurred either on 1 day or repeatedly on 5 successive days. Impairments in auditory function were assessed using distortion product otoacoustic emissions and compound action potential testing. In other rats, tissues were harvested following JP-8 exposure for assessment of hydrocarbon levels or glutathione (GSH) levels. A single JP-8 exposure by itself at 1000 mg/m(3) did not disrupt auditory function. However, exposure to JP-8 and noise produced an additive disruption in outer hair cell function. Repeated 5-day JP-8 exposure at 1000 mg/m(3) for 4 h produced impairment of outer hair cell function that was most evident at the first postexposure assessment time. Partial though not complete recovery was observed over a 4-week postexposure period. The adverse effects of repeated JP-8 exposures on auditory function were inconsistent, but combined treatment with JP-8 + noise yielded greater impairment of auditory function, and hair cell loss than did noise by itself. Qualitative comparison of outer hair cell loss suggests an increase in outer hair cell death among rats treated with JP-8 + noise for 5 days as compared to noise alone. In most instances, hydrocarbon constituents of the fuel

  16. Neonatal isoflurane exposure induces neurocognitive impairment and abnormal hippocampal histone acetylation in mice.

    Directory of Open Access Journals (Sweden)

    Tao Zhong

    Full Text Available Neonatal exposure to isoflurane may induce long-term memory impairment in mice. Histone acetylation is an important form of chromatin modification that regulates the transcription of genes required for memory formation. This study investigated whether neonatal isoflurane exposure-induced neurocognitive impairment is related to dysregulated histone acetylation in the hippocampus and whether it can be attenuated by the histone deacetylase (HDAC inhibitor trichostatin A (TSA.C57BL/6 mice were exposed to 0.75% isoflurane three times (each for 4 h at postnatal days 7, 8, and 9. Contextual fear conditioning (CFC was tested at 3 months after anesthesia administration. TSA was intraperitoneally injected 2 h before CFC training. Hippocampal histone acetylation levels were analyzed following CFC training. Levels of the neuronal activation and synaptic plasticity marker c-Fos were investigated at the same time point.Mice that were neonatally exposed to isoflurane showed significant memory impairment on CFC testing. These mice also exhibited dysregulated hippocampal H4K12 acetylation and decreased c-Fos expression following CFC training. TSA attenuated isoflurane-induced memory impairment and simultaneously increased histone acetylation and c-Fos levels in the hippocampal cornu ammonis (CA1 area 1 h after CFC training.Memory impairment induced by repeated neonatal exposure to isoflurane is associated with dysregulated histone H4K12 acetylation in the hippocampus, which probably affects downstream c-Fos gene expression following CFC training. The HDAC inhibitor TSA successfully rescued impaired contextual fear memory, presumably by promoting histone acetylation and histone acetylation-mediated gene expression.

  17. 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; Hinds, Terry D

    2016-01-01

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

  18. Prenatal exposure to arsenic impairs behavioral flexibility and cortical structure in mice

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    Kyaw Htet eAung

    2016-03-01

    Full Text Available Exposure to arsenic from well water in developing countries is suspected to cause developmental neurotoxicity. Although it has been demonstrated that exposure to sodium arsenite (NaAsO2 suppresses neurite outgrowth of cortical neurons in vitro, it is largely unknown how developmental exposure to NaAsO2 impairs higher brain function and affects cortical histology. Here, we investigated the effect of prenatal NaAsO2 exposure on the behavior of mice in adulthood, and evaluated histological changes in the prelimbic cortex (PrL, which is a part of the medial prefrontal cortex that is critically involved in cognition. Drinking water with or without NaAsO2 (85 ppm was provided to pregnant C3H mice from gestational days 8 to 18, and offspring of both sexes were subjected to cognitive behavioral analyses at 60 weeks of age. The brains of female offspring were subsequently harvested and used for morphometrical analyses. We found that both male and female mice prenatally exposed to NaAsO2 displayed an impaired adaptation to repetitive reversal tasks. In morphometrical analyses of Nissl- or Golgi-stained tissue sections, we found that NaAsO2 exposure was associated with a significant increase in the number of pyramidal neurons in layers V and VI of the PrL, but not other layers of the PrL. More strikingly, prenatal NaAsO2 exposure was associated with a significant decrease in neurite length but not dendrite spine density in all layers of the PrL. Taken together, our results indicate that prenatal exposure to NaAsO2 leads to behavioral inflexibility in adulthood and cortical disarrangement in the PrL might contribute to this behavioral impairment.

  19. Chronic exposure to low frequency noise at moderate levels causes impaired balance in mice.

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    Haruka Tamura

    Full Text Available We are routinely exposed to low frequency noise (LFN; below 0.5 kHz at moderate levels of 60-70 dB sound pressure level (SPL generated from various sources in occupational and daily environments. LFN has been reported to affect balance in humans. However, there is limited information about the influence of chronic exposure to LFN at moderate levels for balance. In this study, we investigated whether chronic exposure to LFN at a moderate level of 70 dB SPL affects the vestibule, which is one of the organs responsible for balance in mice. Wild-type ICR mice were exposed for 1 month to LFN (0.1 kHz and high frequency noise (HFN; 16 kHz at 70 dB SPL at a distance of approximately 10-20 cm. Behavior analyses including rotarod, beam-crossing and footprint analyses showed impairments of balance in LFN-exposed mice but not in non-exposed mice or HFN-exposed mice. Immunohistochemical analysis showed a decreased number of vestibular hair cells and increased levels of oxidative stress in LFN-exposed mice compared to those in non-exposed mice. Our results suggest that chronic exposure to LFN at moderate levels causes impaired balance involving morphological impairments of the vestibule with enhanced levels of oxidative stress. Thus, the results of this study indicate the importance of considering the risk of chronic exposure to LFN at a moderate level for imbalance.

  20. Degree of exposure to domestic violence, psychopathology, and functional impairment in children and adolescents.

    Science.gov (United States)

    Bayarri Fernàndez, Eduard; Ezpeleta, Lourdes; Granero, Roser; de la Osa, Núria; Domènech, Josep María

    2011-04-01

    There are discrepancies about whether children who witness and suffer domestic violence (DV) have similar outcomes in terms of psychopathology. This work examines the relationship between different types of exposure to DV and child psychopathology and functional impairment. One hundred and forty-four Spanish children aged from 4 to 17 years and exposed to DV were evaluated using a diagnostic interview and other instruments of psychopathology and functional impairment. The participants were classified in three groups according to the degree of exposure: witness (n = 72), involved (n = 52), and victim (n = 20). According to mothers' self-reports and mother-child combined information, DV equally affects psychopathology and functional impairment regardless of the degree of the exposure. Children's self-reports showed a linear trend to present greater psychopathology as a victim than as a witness. The differential effect of exposure to DV measured in this study depended on the informant, which underlines the importance of obtaining information from the children exposed to violence at home.

  1. Statins alter the hepatobiliary transport of unconjugated and conjugated bilirubin in sandwich-cultured rat hepatocytes.

    Science.gov (United States)

    Szabó, Mónika; Veres, Zsuzsa; Bátai-Konczos, Attila; Kékesi, Orsolya; Kis, Emese; Szabó, Kitti; Jemnitz, Katalin

    2014-09-01

    Several studies have reported that statins occasionally cause impairment of liver functions characterized by elevated serum bilirubin levels, which might be due to altered function of the multidrug resistance-associated proteins (Mrp2/3). We aimed to study the modulation of the hepatobiliary transport of bilirubin by four statin derivatives, atorvastatin, fluvastatin, pravastatin, and rosuvastatin in sandwich-cultured rat hepatocytes. All statins except pravastatin significantly inhibited the uptake of bilirubin. The biliary efflux of bilirubin conjugates was increased by pravastatin and rosuvastatin concentration dependently. Rosuvastatin stimulated not only the Mrp2 mediated biliary, but the Mrp3 mediated sinusoidal elimination, resulting in decreased intracellular bilirubin accumulation. The significantly induced Mrp2/3 protein levels (ranging from 1.5 to 1.8-fold) accounted for the elevated efflux. Cell polarization, the formation of biliary network was also significantly increased by fluvastatin, pravastatin and rosuvastatin (151%, 216% and 275% of the control, respectively). The simultaneous inhibition of the uptake and the stimulation of the sinusoidal and canalicular elimination may explain, at least in part, the clinical observation of elevated serum bilirubin levels. In conclusion, our results suggest that in spite of the elevated serum bilirubin levels, the altered Mrp2 and Mrp3 functions by statins is probably not associated with hepatotoxic effects.

  2. Exercise Prevents Memory Impairment Induced by Arsenic Exposure in Mice: Implication of Hippocampal BDNF and CREB.

    Science.gov (United States)

    Sun, Bao-Fei; Wang, Qing-Qing; Yu, Zi-Jiang; Yu, Yan; Xiao, Chao-Lun; Kang, Chao-Sheng; Ge, Guo; Linghu, Yan; Zhu, Jun-De; Li, Yu-Mei; Li, Qiang-Ming; Luo, Shi-Peng; Yang, Dang; Li, Lin; Zhang, Wen-Yan; Tian, Guang

    2015-01-01

    High concentrations of arsenic, which can be occasionally found in drinking water, have been recognized as a global health problem. Exposure to arsenic can disrupt spatial memory; however, the underlying mechanism remains unclear. In the present study, we tested whether exercise could interfere with the effect of arsenic exposure on the long-term memory (LTM) of object recognition in mice. Arsenic (0, 1, 3, and 10 mg/ kg, i.g.) was administered daily for 12 weeks. We found that arsenic at dosages of 1, 3, and 10 mg/kg decreased body weight and increased the arsenic content in the brain. The object recognition LTM (tested 24 h after training) was disrupted by 3 mg/ kg and 10 mg/ kg, but not 1 mg/ kg arsenic exposure. Swimming exercise also prevented LTM impairment induced by 3 mg/ kg, but not with 10 mg/ kg, of arsenic exposure. The expression of brain-derived neurotrophic factor (BDNF) and phosphorylated cAMP-response element binding protein (pCREB) in the CA1 and dentate gyrus areas (DG) of the dorsal hippocampus were decreased by 3 mg/ kg and 10 mg/ kg, but not by 1 mg/ kg, of arsenic exposure. The decrease in BDNF and pCREB in the CA1 and DG induced by 3 mg/ kg, but not 10 mg/ kg, of arsenic exposure were prevented by swimming exercise. Arsenic exposure did not affect the total CREB expression in the CA1 or DG. Taken together, these results indicated that swimming exercise prevented the impairment of object recognition LTM induced by arsenic exposure, which may be mediated by BDNF and CREB in the dorsal hippocampus.

  3. Exercise Prevents Memory Impairment Induced by Arsenic Exposure in Mice: Implication of Hippocampal BDNF and CREB.

    Directory of Open Access Journals (Sweden)

    Bao-Fei Sun

    Full Text Available High concentrations of arsenic, which can be occasionally found in drinking water, have been recognized as a global health problem. Exposure to arsenic can disrupt spatial memory; however, the underlying mechanism remains unclear. In the present study, we tested whether exercise could interfere with the effect of arsenic exposure on the long-term memory (LTM of object recognition in mice. Arsenic (0, 1, 3, and 10 mg/ kg, i.g. was administered daily for 12 weeks. We found that arsenic at dosages of 1, 3, and 10 mg/kg decreased body weight and increased the arsenic content in the brain. The object recognition LTM (tested 24 h after training was disrupted by 3 mg/ kg and 10 mg/ kg, but not 1 mg/ kg arsenic exposure. Swimming exercise also prevented LTM impairment induced by 3 mg/ kg, but not with 10 mg/ kg, of arsenic exposure. The expression of brain-derived neurotrophic factor (BDNF and phosphorylated cAMP-response element binding protein (pCREB in the CA1 and dentate gyrus areas (DG of the dorsal hippocampus were decreased by 3 mg/ kg and 10 mg/ kg, but not by 1 mg/ kg, of arsenic exposure. The decrease in BDNF and pCREB in the CA1 and DG induced by 3 mg/ kg, but not 10 mg/ kg, of arsenic exposure were prevented by swimming exercise. Arsenic exposure did not affect the total CREB expression in the CA1 or DG. Taken together, these results indicated that swimming exercise prevented the impairment of object recognition LTM induced by arsenic exposure, which may be mediated by BDNF and CREB in the dorsal hippocampus.

  4. Impaired contextual fear extinction and hippocampal synaptic plasticity in adult rats induced by prenatal morphine exposure.

    Science.gov (United States)

    Tan, Ji-Wei; Duan, Ting-Ting; Zhou, Qi-Xin; Ding, Ze-Yang; Jing, Liang; Cao, Jun; Wang, Li-Ping; Mao, Rong-Rong; Xu, Lin

    2015-07-01

    Prenatal opiate exposure causes a series of neurobehavioral disturbances by affecting brain development. However, the question of whether prenatal opiate exposure increases vulnerability to memory-related neuropsychiatric disorders in adult offspring remains largely unknown. Here, we found that rats prenatally exposed to morphine (PM) showed impaired acquisition but enhanced maintenance of contextual fear memory compared with control animals that were prenatally exposed to saline (PS). The impairment of acquisition was rescued by increasing the intensity of footshocks (1.2 mA rather than 0.8 mA). Meanwhile, we also found that PM rats exhibited impaired extinction of contextual fear, which is associated with enhanced maintenance of fear memory. The impaired extinction lasted for 1 week following extinction training. Furthermore, PM rats exhibited reduced anxiety-like behavior in the elevated plus-maze and light/dark box test without differences in locomotor activity. These alterations in PM rats were mirrored by abnormalities in synaptic plasticity in the Schaffer collateral-CA1 synapses of the hippocampus in vivo. PS rats showed blocked long-term potentiation and enabled long-term depression in CA1 synapses following contextual fear conditioning, while prenatal morphine exposure restricted synaptic plasticity in CA1 synapses. The smaller long-term potentiation in PM rats was not further blocked by contextual fear conditioning, and the long-term depression enabled by contextual fear conditioning was abolished. Taken together, our results provide the first evidence suggesting that prenatal morphine exposure may increase vulnerability to fear memory-related neuropsychiatric disorders in adulthood.

  5. Environmental Exposure to Cadmium: Health Risk Assessment and its Associations with Hypertension and Impaired Kidney Function

    Science.gov (United States)

    Wu, Haiyun; Liao, Qilin; Chillrud, Steven N.; Yang, Qiang; Huang, Lei; Bi, Jun; Yan, Beizhan

    2016-07-01

    Cadmium (Cd) is a toxic metal. This study was aimed to estimate the potential health risks in a Cd-polluted district in China, and examine the relationship between urinary cadmium(UCd) and hypertension and impaired kidney function at low exposure levels (UCd: GM 1.3 μg/g creatinine). Blood pressure measurement, questionnaires, and collection of urinary samples were conducted from 217 residents. Environmental samples, food, and cigarette samples were collected and detected to estimate the risks posed by Cd and the contribution of inhalation, ingestion, and dermal contact pathways to these risks. A logistic regression model was used in examining associations between exposure and hypertension and impaired kidney function. Results show that this population is at high risk. For non-smokers, incremental lifetime cancer risk (ILCR) and hazard quotient (HQ) are 1.74E-04 and 2.96, and for smokers, they are 1.07E-03 and 52.5, respectively. Among all exposure pathways, smoking and foods cause the major increases in ILCR and HQ. UCd is significantly associated with hypertension (odds ratio (OR) = 1.468 95% confidence interval (CI): 1.104, 1.953; P = 0.008) and impaired kidney function (OR = 1.902, 95% CI: 1.054, 3.432; P = 0.033). The results demonstrate that Cd can potentially lead to adverse health effects.

  6. 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.

    2008-01-01

    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 neuro

  7. Bumblebee learning and memory is impaired by chronic exposure to a neonicotinoid pesticide.

    Science.gov (United States)

    Stanley, Dara A; Smith, Karen E; Raine, Nigel E

    2015-11-16

    Bumblebees are exposed to pesticides applied for crop protection while foraging on treated plants, with increasing evidence suggesting that this sublethal exposure has implications for pollinator declines. The challenges of navigating and learning to manipulate many different flowers underline the critical role learning plays for the foraging success and survival of bees. We assessed the impacts of both acute and chronic exposure to field-realistic levels of a widely applied neonicotinoid insecticide, thiamethoxam, on bumblebee odour learning and memory. Although bees exposed to acute doses showed conditioned responses less frequently than controls, we found no difference in the number of individuals able to learn at field-realistic exposure levels. However, following chronic pesticide exposure, bees exposed to field-realistic levels learnt more slowly and their short-term memory was significantly impaired following exposure to 2.4 ppb pesticide. These results indicate that field-realistic pesticide exposure can have appreciable impacts on learning and memory, with potential implications for essential individual behaviour and colony fitness.

  8. 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.

  9. 77 FR 12837 - Notice of Release of the Exposure Draft, Accounting for Impairment of General Property, Plant...

    Science.gov (United States)

    2012-03-02

    ... From the Federal Register Online via the Government Publishing Office FEDERAL ACCOUNTING STANDARDS ADVISORY BOARD Notice of Release of the Exposure Draft, Accounting for Impairment of General Property, Plant, and Equipment Remaining in Use AGENCY: Federal Accounting Standards Advisory Board....

  10. Exposure to Mozart music reduces cognitive impairment in pilocarpine-induced status epilepticus rats.

    Science.gov (United States)

    Xing, Yingshou; Qin, Yi; Jing, Wei; Zhang, Yunxiang; Wang, Yanran; Guo, Daqing; Xia, Yang; Yao, Dezhong

    2016-02-01

    Patients with temporal lobe epilepsy (TLE) often display cognitive deficits. However, current epilepsy therapeutic interventions mainly aim at how to reduce the frequency and degree of epileptic seizures. Recovery of cognitive impairment is not attended enough, resulting in the lack of effective approaches in this respect. In the pilocarpine-induced temporal lobe epilepsy rat model, memory impairment has been classically reported. Here we evaluated spatial cognition changes at different epileptogenesis stages in rats of this model and explored the effects of long-term Mozart music exposure on the recovery of cognitive ability. Our results showed that pilocarpine rats suffered persisting cognitive impairment during epileptogenesis. Interestingly, we found that Mozart music exposure can significantly enhance cognitive ability in epileptic rats, and music intervention may be more effective for improving cognitive function during the early stages after Status epilepticus. These findings strongly suggest that Mozart music may help to promote the recovery of cognitive damage due to seizure activities, which provides a novel intervention strategy to diminish cognitive deficits in TLE patients.

  11. 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

  12. Exposure to lipophilic chemicals as a cause of neurological impairments, neurodevelopmental disorders and neurodegenerative diseases.

    Science.gov (United States)

    Zeliger, Harold I

    2013-09-01

    Many studies have associated environmental exposure to chemicals with neurological impairments (NIs) including neuropathies, cognitive, motor and sensory impairments; neurodevelopmental disorders (NDDs) including autism and attention deficit hyperactivity disorder (ADHD); neurodegenerative diseases (NDGs) including Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis (ALS). The environmental chemicals shown to induce all these diseases include persistent organic pollutants (POPs), the plastic exudates bisphenol A and phthalates, low molecular weight hydrocarbons (LMWHCs) and polynuclear aromatic hydrocarbons (PAHs). It is reported here that though these chemicals differ widely in their chemical properties, reactivities and known points of attack in humans, a common link does exist between them. All are lipophilic species found in serum and they promote the sequential absorption of otherwise non-absorbed toxic hydrophilic species causing these diseases.

  13. Prenatal cocaine exposure impairs cognitive function of progeny via insulin growth factor II epigenetic regulation.

    Science.gov (United States)

    Zhao, Qian; Hou, Jing; Chen, Bo; Shao, Xue; Zhu, Ruiming; Bu, Qian; Gu, Hui; Li, Yan; Zhang, Baolai; Du, Changman; Fu, Dengqi; Kong, Jueying; Luo, Li; Long, Hailei; Li, Hongyu; Deng, Yi; Zhao, Yinglan; Cen, Xiaobo

    2015-10-01

    Studies have showed that prenatal cocaine exposure (PCOC) can impair cognitive function and social behavior of the offspring; however, the mechanism underlying such effect is poorly understood. Insulin-like growth factor II (Igf-II), an imprinted gene, has a critical role in memory consolidation and enhancement. We hypothesized that epigenetic regulation of hippocampal Igf-II may attribute to the cognitive deficits of PCOC offspring. We used Morris water maze and open-field task to test the cognitive function in PCOC offspring. The epigenetic alteration involved in hippocampal Igf-II expression deficit in PCOC offspring was studied by determining Igf-II methylation status, DNA methyltransferases (DNMT) expressions and L-methionine level. Moreover, IGF-II rescue experiments were performed and the downstream signalings were investigated in PCOC offspring. In behavioral tests, we observed impaired spatial learning and memory and increased anxiety in PCOC offspring; moreover, hippocampal IGF-II mRNA and protein expressions were significantly decreased. Hippocampal methylation of cytosine-phospho-guanine (CpG) dinucleotides in differentially methylated region (DMR) 2 of Igf-II was elevated in PCOC offspring, which may be driven by the upregulation of L-methionine and DNA methyltransferase (DNMT) 1. Importantly, intra-hippocampal injection of recombinant IGF-II reactivated the repressed calcium calmodulin kinase II α (CaMKIIα) and reversed cognitive deficits in PCOC offspring. Collectively, our findings suggest that cocaine exposure during pregnancy impairs cognitive function of offspring through epigenetic modification of Igf-II gene. Enhancing IGF-II signaling may represent a novel therapeutical strategy for cocaine-induced cognitive impairment.

  14. Alcohol exposure after mild focal traumatic brain injury impairs neurological recovery and exacerbates localized neuroinflammation.

    Science.gov (United States)

    Teng, Sophie X; Katz, Paige S; Maxi, John K; Mayeux, Jacques P; Gilpin, Nicholas W; Molina, Patricia E

    2015-03-01

    Traumatic brain injury (TBI) represents a leading cause of morbidity and mortality among young individuals. Alcohol abuse is a risk factor associated with increased TBI incidence. In addition, up to 26% of TBI patients engage in alcohol consumption after TBI. Limited preclinical studies have examined the impact of post-injury alcohol exposure on TBI recovery. The aim of this study was to determine the isolated and combined effects of TBI and alcohol on cognitive, behavioral, and physical recovery, as well as on associated neuroinflammatory changes. Male Sprague-Dawley rats (∼300g) were subjected to a mild focal TBI by lateral fluid percussion (∼30PSI, ∼25ms) under isoflurane anesthesia. On day 4 after TBI, animals were exposed to either sub-chronic intermittent alcohol vapor (95% ethanol 14h on/10h off; BAL∼200mg/dL) or room air for 10days. TBI induced neurological dysfunction reflected by an increased neurological severity score (NSS) showed progressive improvement in injured animals exposed to room air (TBI/air). In contrast, TBI animals exposed to alcohol vapor (TBI/alcohol) showed impaired NSS recovery throughout the 10-day period of alcohol exposure. Open-field exploration test revealed an increased anxiety-like behavior in TBI/alcohol group compared to TBI/air group. Additionally, alcohol-exposed animals showed decreased locomotion and impaired novel object recognition. Immunofluorescence showed enhanced reactive astrocytes, microglial activation, and HMGB1 expression localized to the injured cortex of TBI/alcohol as compared to TBI/air animals. The expression of neuroinflammatory markers showed significant positive correlation with NSS. These findings indicated a close relationship between accentuated neuroinflammation and impaired neurological recovery from post-TBI alcohol exposure. The clinical implications of long-term consequences in TBI patients exposed to alcohol during recovery warrant further investigation.

  15. Exposure to multiple cholinergic pesticides impairs olfactory learning and memory in honeybees.

    Science.gov (United States)

    Williamson, Sally M; Wright, Geraldine A

    2013-05-15

    Pesticides are important agricultural tools often used in combination to avoid resistance in target pest species, but there is growing concern that their widespread use contributes to the decline of pollinator populations. Pollinators perform sophisticated behaviours while foraging that require them to learn and remember floral traits associated with food, but we know relatively little about the way that combined exposure to multiple pesticides affects neural function and behaviour. The experiments reported here show that prolonged exposure to field-realistic concentrations of the neonicotinoid imidacloprid and the organophosphate acetylcholinesterase inhibitor coumaphos and their combination impairs olfactory learning and memory formation in the honeybee. Using a method for classical conditioning of proboscis extension, honeybees were trained in either a massed or spaced conditioning protocol to examine how these pesticides affected performance during learning and short- and long-term memory tasks. We found that bees exposed to imidacloprid, coumaphos, or a combination of these compounds, were less likely to express conditioned proboscis extension towards an odor associated with reward. Bees exposed to imidacloprid were less likely to form a long-term memory, whereas bees exposed to coumaphos were only less likely to respond during the short-term memory test after massed conditioning. Imidacloprid, coumaphos and a combination of the two compounds impaired the bees' ability to differentiate the conditioned odour from a novel odour during the memory test. Our results demonstrate that exposure to sublethal doses of combined cholinergic pesticides significantly impairs important behaviours involved in foraging, implying that pollinator population decline could be the result of a failure of neural function of bees exposed to pesticides in agricultural landscapes.

  16. Impairment on sperm quality and fertility of adult rats after antiandrogen exposure during prepuberty.

    Science.gov (United States)

    Perobelli, Juliana Elaine; Alves, Thaís Regina; de Toledo, Fabíola Choqueta; Fernandez, Carla Dal Bianco; Anselmo-Franci, Janete A; Klinefelter, Gary R; Kempinas, Wilma De Grava

    2012-06-01

    This study evaluated the effects of antiandrogen exposure during the prepubertal period on reproductive development and reproductive competence in adults. Male rats were divided into two groups: flutamide, receiving 25 mg/kg/day of flutamide by oral gavage and control, receiving vehicle daily. Dosing continued from PND 21 to 44, and animals were killed on PND 50 or PND 75-80. The epididymis, prostate, vas deferens and seminal vesicle weights were lower in Flutamide group on PND 50, while on PND 80 only seminal vesicle weight was reduced. Fertility assessed by IUI revealed a decrease in the fertility potential in the flutamide-treated adults. Flutamide accelerated sperm transit time through the epididymis, impairing sperm motility and storage. A quantitative analysis of the cauda sperm membrane proteome revealed a few significant changes in protein expression. Thus, exposure to flutamide during the prepubertal period compromises the function of the epididymis along with epididymal sperm quality at adulthood.

  17. Early postnatal nicotine exposure causes hippocampus-dependent memory impairments in adolescent mice: Association with altered nicotinic cholinergic modulation of LTP, but not impaired LTP.

    Science.gov (United States)

    Nakauchi, Sakura; Malvaez, Melissa; Su, Hailing; Kleeman, Elise; Dang, Richard; Wood, Marcelo A; Sumikawa, Katumi

    2015-02-01

    Fetal nicotine exposure from smoking during pregnancy causes long-lasting cognitive impairments in offspring, yet little is known about the mechanisms that underlie this effect. Here we demonstrate that early postnatal exposure of mouse pups to nicotine via maternal milk impairs long-term, but not short-term, hippocampus-dependent memory during adolescence. At the Schaffer collateral (SC) pathway, the most widely studied synapses for a cellular correlate of hippocampus-dependent memory, the induction of N-methyl-D-aspartate receptor-dependent transient long-term potentiation (LTP) and protein synthesis-dependent long-lasting LTP are not diminished by nicotine exposure, but rather unexpectedly the threshold for LTP induction becomes lower after nicotine treatment. Using voltage sensitive dye to visualize hippocampal activity, we found that early postnatal nicotine exposure also results in enhanced CA1 depolarization and hyperpolarization after SC stimulation. Furthermore, we show that postnatal nicotine exposure induces pervasive changes to the nicotinic modulation of CA1 activity: activation of nicotinic receptors no longer increases CA1 network depolarization, acute nicotine inhibits rather than facilitates the induction of LTP at the SC pathway by recruiting an additional nicotinic receptor subtype, and acute nicotine no longer blocks LTP induction at the temporoammonic pathway. These findings reflect the pervasive impact of nicotine exposure during hippocampal development, and demonstrate an association of hippocampal memory impairments with altered nicotinic cholinergic modulation of LTP, but not impaired LTP. The implication of our results is that nicotinic cholinergic-dependent plasticity is required for long-term memory formation and that postnatal nicotine exposure disrupts this form of plasticity.

  18. Cognitive impairment in rats after long-term exposure to GSM-900 mobile phone radiation.

    Science.gov (United States)

    Nittby, Henrietta; Grafström, Gustav; Tian, Dong Ping; Malmgren, Lars; Brun, Arne; Persson, Bertil R R; Salford, Leif G; Eberhardt, Jacob

    2008-04-01

    Considering the frequent use of mobile phones, we have directed attention to possible implications on cognitive functions. In this study we investigated in a rat model the long-term effects of protracted exposure to Global System for Mobile Communication-900 MHz (GSM-900) radiation. Out of a total of 56 rats, 32 were exposed for 2 h each week for 55 weeks to radio-frequency electromagnetic radiation at different SAR levels (0.6 and 60 mW/kg at the initiation of the experimental period) emitted by a (GSM-900) test phone. Sixteen animals were sham exposed and eight animals were cage controls, which never left the animal house. After this protracted exposure, GSM-900 exposed rats were compared to sham exposed controls. Effects on exploratory behaviour were evaluated in the open-field test, in which no difference was seen. Effects on cognitive functions were evaluated in the episodic-like memory test. In our study, GSM exposed rats had impaired memory for objects and their temporal order of presentation, compared to sham exposed controls (P = 0.02). Detecting the place in which an object was presented was not affected by GSM exposure. Our results suggest significantly reduced memory functions in rats after GSM microwave exposure (P = 0.02).

  19. Drone exposure to the systemic insecticide Fipronil indirectly impairs queen reproductive potential

    Science.gov (United States)

    Kairo, Guillaume; Provost, Bertille; Tchamitchian, Sylvie; Ben Abdelkader, Faten; Bonnet, Marc; Cousin, Marianne; Sénéchal, Jacques; Benet, Pauline; Kretzschmar, André; Belzunces, Luc P.; Brunet, Jean-Luc

    2016-01-01

    A species that requires sexual reproduction but cannot reproduce is doomed to extinction. The important increasing loss of species emphasizes the ecological significance of elucidating the effects of environmental stressors, such as pesticides, on reproduction. Despite its special reproductive behavior, the honey bee was selected as a relevant and integrative environmental model because of its constant and diverse exposure to many stressors due to foraging activity. The widely used insecticide Fipronil, the use of which is controversial because of its adverse effects on honey bees, was chosen to expose captive drones in hives via syrup contaminated at 0.1 μg/L and gathered by foragers. Such environmental exposure led to decreased spermatozoa concentration and sperm viability coupled with an increased sperm metabolic rate, resulting in drone fertility impairment. Subsequently, unexposed queens inseminated with such sperm exhibited fewer spermatozoa with lower viability in their spermatheca, leaving no doubt about the detrimental consequences for the reproductive potential of queens, which are key for colony sustainability. These findings suggest that pesticides could contribute to declining honey bee populations through fertility impairment, as exemplified by Fipronil. More broadly, reproductive disorders should be taken into consideration when investigating the decline of other species. PMID:27549030

  20. Drone exposure to the systemic insecticide Fipronil indirectly impairs queen reproductive potential.

    Science.gov (United States)

    Kairo, Guillaume; Provost, Bertille; Tchamitchian, Sylvie; Ben Abdelkader, Faten; Bonnet, Marc; Cousin, Marianne; Sénéchal, Jacques; Benet, Pauline; Kretzschmar, André; Belzunces, Luc P; Brunet, Jean-Luc

    2016-08-23

    A species that requires sexual reproduction but cannot reproduce is doomed to extinction. The important increasing loss of species emphasizes the ecological significance of elucidating the effects of environmental stressors, such as pesticides, on reproduction. Despite its special reproductive behavior, the honey bee was selected as a relevant and integrative environmental model because of its constant and diverse exposure to many stressors due to foraging activity. The widely used insecticide Fipronil, the use of which is controversial because of its adverse effects on honey bees, was chosen to expose captive drones in hives via syrup contaminated at 0.1 μg/L and gathered by foragers. Such environmental exposure led to decreased spermatozoa concentration and sperm viability coupled with an increased sperm metabolic rate, resulting in drone fertility impairment. Subsequently, unexposed queens inseminated with such sperm exhibited fewer spermatozoa with lower viability in their spermatheca, leaving no doubt about the detrimental consequences for the reproductive potential of queens, which are key for colony sustainability. These findings suggest that pesticides could contribute to declining honey bee populations through fertility impairment, as exemplified by Fipronil. More broadly, reproductive disorders should be taken into consideration when investigating the decline of other species.

  1. Impairment in Spatial Memory in adult Rats following developmental Low Lead Exposure

    Directory of Open Access Journals (Sweden)

    Rajashekar Rao Barkur

    2012-11-01

    Full Text Available The present study was aimed to investigate the effect of environmentally relevant levels of lead exposure during gestational and early postnatal period on hippocampal dependent spatial memory in rats during adulthood. The pregnant rats were allowed to drink either normal water (control group or 0.2% lead acetate solution (Leadtreated group during pregnancy and lactation. Thus rats pups of lead treated group where exposed to lead indirectly through their mothers during this period. At weaning pups of lead treated group were allowed to drink normal water till they attain the adult hood. Blood lead level was estimated on postnatal day 22 and 120. Birth weight and weight gain of the rat pups as they grew were measured at regular intervals. Both the control and lead treated groups of rats were subjected to water maze test on postnatal day 30 and 120. Results showed that lead treatment had no effect on birth weight or weight gain. Blood lead level on postnatal day 22 was significantly high in treated group compared to the control group and it was normalized by end of four months. The rats born to lead treated mothers showed impaired in spatial memory during water maze test both on postnatal day 36 and 126. These data suggests that exposure to environmentally relevant levels of lead during intrauterine and early postnatal period of brain development causes impairment in spatial memory not only during infancy but also lasts till adulthood.

  2. Drone exposure to the systemic insecticide Fipronil indirectly impairs queen reproductive potential

    Science.gov (United States)

    Kairo, Guillaume; Provost, Bertille; Tchamitchian, Sylvie; Ben Abdelkader, Faten; Bonnet, Marc; Cousin, Marianne; Sénéchal, Jacques; Benet, Pauline; Kretzschmar, André; Belzunces, Luc P.; Brunet, Jean-Luc

    2016-08-01

    A species that requires sexual reproduction but cannot reproduce is doomed to extinction. The important increasing loss of species emphasizes the ecological significance of elucidating the effects of environmental stressors, such as pesticides, on reproduction. Despite its special reproductive behavior, the honey bee was selected as a relevant and integrative environmental model because of its constant and diverse exposure to many stressors due to foraging activity. The widely used insecticide Fipronil, the use of which is controversial because of its adverse effects on honey bees, was chosen to expose captive drones in hives via syrup contaminated at 0.1 μg/L and gathered by foragers. Such environmental exposure led to decreased spermatozoa concentration and sperm viability coupled with an increased sperm metabolic rate, resulting in drone fertility impairment. Subsequently, unexposed queens inseminated with such sperm exhibited fewer spermatozoa with lower viability in their spermatheca, leaving no doubt about the detrimental consequences for the reproductive potential of queens, which are key for colony sustainability. These findings suggest that pesticides could contribute to declining honey bee populations through fertility impairment, as exemplified by Fipronil. More broadly, reproductive disorders should be taken into consideration when investigating the decline of other species.

  3. Bilirubin Oxidase Activity of Bacillus subtilis CotA

    OpenAIRE

    Sakasegawa, S; Ishikawa, H.; Imamura, S.; Sakuraba, H.; Goda, S.; Ohshima, T.

    2006-01-01

    The spore coat protein CotA from Bacillus subtilis was previously identified as a laccase. We have now found that CotA also shows strong bilirubin oxidase activity and markedly higher affinity for bilirubin than conventional bilirubin oxidase. This is the first characterization of bilirubin oxidase activity in a bacterial protein.

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

    Science.gov (United States)

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

    2007-06-01

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

  5. 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.

  6. Role of carbon monoxide in impaired endothelial function mediated by acute second-hand tobacco, incense, and candle smoke exposures.

    Science.gov (United States)

    Weber, Lynn P; Al-Dissi, Ahmad; Marit, Jordan S; German, Timothy N; Terletski, Sharilyn D

    2011-05-01

    The aim of this study was to determine if carbon monoxide (CO) is responsible for acute adverse cardiovascular effects of different sources of smoke: second-hand tobacco smoke (SHS), incense and candle smoke. Endothelial function was tested using flow-mediated dilation (FMD) in pigs and was shown to be sensitive to nitric oxide synthase blockade. Subsequent experiments showed that FMD was significantly impaired compared to sham-exposed pigs at 30 min after a 30-min exposure to all three sources of smoke. In contrast, SHS significantly increased systolic, diastolic and pulse pressures compared to sham-exposure, while both incense and candle smoke exposure had no effect. The FMD impairment correlated well with CO levels in the exposure chamber, but not total particulates or venous CO-hemoglobin. Therefore, this study suggests a gas phase component of smoke that accompanies CO, but not CO itself, is responsible for acute endothelial dysfunction after SHS, incense or candle smoke exposure.

  7. 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.

  8. Maternal LPS exposure during pregnancy impairs testicular development, steroidogenesis and spermatogenesis in male offspring.

    Science.gov (United States)

    Wang, Hua; Yang, Lu-Lu; Hu, Yong-Fang; Wang, Bi-Wei; Huang, Yin-Yin; Zhang, Cheng; Chen, Yuan-Hua; Xu, De-Xiang

    2014-01-01

    Lipopolysaccharide (LPS) is associated with adverse developmental outcomes including embryonic resorption, fetal death, congenital teratogenesis and fetal growth retardation. Here, we explored the effects of maternal LPS exposure during pregnancy on testicular development, steroidogenesis and spermatogenesis in male offspring. The pregnant mice were intraperitoneally injected with LPS (50 µg/kg) daily from gestational day (GD) 13 to GD 17. At fetal period, a significant decrease in body weight and abnormal Leydig cell aggregations were observed in males whose mothers were exposed to LPS during pregnancy. At postnatal day (PND) 26, anogenital distance (AGD), a sensitive index of altered androgen action, was markedly reduced in male pups whose mothers were exposed to LPS daily from GD13 to GD 17. At PND35, the weight of testes, prostates and seminal vesicles, and serum testosterone (T) level were significantly decreased in LPS-treated male pups. At adulthood, the number of sperm was significantly decreased in male offspring whose mothers were exposed to LPS on GD 13-17. Maternal LPS exposure during gestation obviously diminished the percent of seminiferous tubules in stages I-VI, increased the percent of seminiferous tubules in stages IX-XII, and caused massive sloughing of germ cells in seminiferous tubules in mouse testes. Moreover, maternal LPS exposure significantly reduced serum T level in male mice whose mothers were exposed to LPS challenge during pregnancy. Taken together, these results suggest that maternal LPS exposure during pregnancy disrupts T production. The decreased T synthesis might be associated with LPS-induced impairments for spermatogenesis in male offspring.

  9. Noise exposure and hearing impairment among Chinese restaurant workers and entertainment employees in Hong Kong.

    Directory of Open Access Journals (Sweden)

    Xiang Qian Lao

    Full Text Available BACKGROUND: Noise-induced hearing loss (NIHL is a major concern in the non-manufacturing industries. This study aimed to investigate the occupational noise exposure and the NIHL among Chinese restaurant workers and entertainment employees working in the service industry in Hong Kong. METHODS: This cross-sectional survey involved a total of 1,670 participants. Among them, 937 were randomly selected from the workers of Chinese restaurants and 733 were selected from workers in three entertainment sectors: radio and television stations; cultural performance halls or auditoria of the Leisure and Cultural Services Department (LCSD; and karaoke bars. Noise exposure levels were measured in the sampled restaurants and entertainment sectors. Each participant received an audiometric screening test. Those who were found to have abnormalities were required to take another diagnostic test in the health center. The "Klockhoff digit" method was used to classify NIHL in the present study. RESULTS: The main source of noise inside restaurants was the stoves. The mean hearing thresholds showed a typical dip at 3 to 6 KHz and a substantial proportion (23.7% of the workers fulfilled the criteria for presumptive NIHL. For entertainment sectors, employees in radio and television stations generally had higher exposure levels than those in the halls or auditoria of the LCSD and karaoke bars. The mean hearing thresholds showed a typical dip at 6 KHz and a substantial proportion of the employees fulfilled the criteria for presumptive NIHL (38.6%, 95%CI: 35.1-42.1%. Being male, older, and having longer service and daily alcohol consumption were associated with noise-induced hearing impairment both in restaurant workers and entertainment employees. CONCLUSION: Excessive noise exposure is common in the Chinese restaurant and entertainment industries and a substantial proportion of restaurant workers and entertainment employees suffer from NIHL. Comprehensive hearing

  10. Maternal LPS exposure during pregnancy impairs testicular development, steroidogenesis and spermatogenesis in male offspring.

    Directory of Open Access Journals (Sweden)

    Hua Wang

    Full Text Available Lipopolysaccharide (LPS is associated with adverse developmental outcomes including embryonic resorption, fetal death, congenital teratogenesis and fetal growth retardation. Here, we explored the effects of maternal LPS exposure during pregnancy on testicular development, steroidogenesis and spermatogenesis in male offspring. The pregnant mice were intraperitoneally injected with LPS (50 µg/kg daily from gestational day (GD 13 to GD 17. At fetal period, a significant decrease in body weight and abnormal Leydig cell aggregations were observed in males whose mothers were exposed to LPS during pregnancy. At postnatal day (PND 26, anogenital distance (AGD, a sensitive index of altered androgen action, was markedly reduced in male pups whose mothers were exposed to LPS daily from GD13 to GD 17. At PND35, the weight of testes, prostates and seminal vesicles, and serum testosterone (T level were significantly decreased in LPS-treated male pups. At adulthood, the number of sperm was significantly decreased in male offspring whose mothers were exposed to LPS on GD 13-17. Maternal LPS exposure during gestation obviously diminished the percent of seminiferous tubules in stages I-VI, increased the percent of seminiferous tubules in stages IX-XII, and caused massive sloughing of germ cells in seminiferous tubules in mouse testes. Moreover, maternal LPS exposure significantly reduced serum T level in male mice whose mothers were exposed to LPS challenge during pregnancy. Taken together, these results suggest that maternal LPS exposure during pregnancy disrupts T production. The decreased T synthesis might be associated with LPS-induced impairments for spermatogenesis in male offspring.

  11. Neurobehavioral impairments produced by developmental lead exposure persisted for generations in zebrafish (Danio rerio).

    Science.gov (United States)

    Xu, Xiaojuan; Weber, Daniel; Burge, Rebekah; VanAmberg, Kelsey

    2016-01-01

    The zebrafish has become a useful animal model for studying the effects of environmental contaminants on neurobehavioral development due to its ease of breeding, high number of eggs per female, short generation times, and a well-established avoidance conditioning paradigm. Using avoidance conditioning as the behavioral paradigm, the present study investigated the effects of embryonic exposure to lead (Pb) on learning in adult zebrafish and the third (F3) generation of those fish. In Experiment 1, adult zebrafish that were developmentally exposed to 0.0, 0.1, 1.0 or 10.0μM Pb (2-24h post fertilization) as embryos were trained and tested for avoidance responses. The results showed that adult zebrafish hatched from embryos exposed to 0.0 or 0.1μM Pb learned avoidance responses during training and displayed significantly increased avoidance responses during testing, while those hatched from embryos exposed to 1.0 or 10.0μM Pb displayed no significant increases in avoidance responses from training to testing. In Experiment 2, the F3 generation of zebrafish that were developmentally exposed to an identical exposure regimen as in Experiment 1 were trained and tested for avoidance responses. The results showed that the F3 generation of zebrafish developmentally exposed as embryos to 0.0 or 0.1μM Pb learned avoidance responses during training and displayed significantly increased avoidance responses during testing, while the F3 generation of zebrafish developmentally exposed as embryos to 1.0 or 10.0μM Pb displayed no significant changes in avoidance responses from training to testing. Thus, developmental Pb exposure produced learning impairments that persisted for at least three generations, demonstrating trans-generational effects of embryonic exposure to Pb.

  12. Characterization of the cognitive impairments induced by prenatal exposure to stress in the rat

    Directory of Open Access Journals (Sweden)

    Julie A. Markham

    2010-11-01

    Full Text Available We have previously shown that male rats exposed to gestational stress exhibit phenotypes resembling what is observed in schizophrenia, including hypersensitivity to amphetamine, blunted sensory gating, disrupted social behavior, impaired stress axis regulation, and aberrant prefrontal expression of genes involved in synaptic plasticity. Maternal psychological stress during pregnancy has been associated with adverse cognitive outcomes among children, as well as an increased risk for developing schizophrenia, which is characterized by significant cognitive deficits. We sought to characterize the long-term cognitive outcome of prenatal stress using a preclinical paradigm, which is readily amenable to the development of novel therapeutic strategies. Rats exposed to repeated variable prenatal stress during the third week of gestation were evaluated using a battery of cognitive tests, including the novel object recognition task, cued and contextual fear conditioning, the Morris water maze, and iterative versions of a paradigm in which working and reference memory for both objects and spatial locations can be assessed (the ‘Can Test’. Prenatally stressed males were impaired relative to controls on each of these tasks, confirming the face validity of this preclinical paradigm and extending the cognitive implications of prenatal stress exposure beyond the hippocampus. Interestingly, in experiments where both sexes were included, the performance of females was found to be less affected by prenatal stress compared to that of males. This could be related to the finding that women are less vulnerable than men to schizophrenia, and merits further investigation.

  13. Memory impairment due to fipronil pesticide exposure occurs at the GABAA receptor level, in rats.

    Science.gov (United States)

    Godinho, Antonio Francisco; de Oliveira Souza, Ana Carolina; Carvalho, Caio Cristóvão; Horta, Daniel França; De Fraia, Daniel; Anselmo, Fabio; Chaguri, João Leandro; Faria, Caique Aparecido

    2016-10-15

    Fipronil (F) a pesticide considered of second generation cause various toxic effects in target and non-target organisms including humans in which provoke neurotoxicity, having the antagonism of gamma-amino butyric acid (GABA) as their main mechanism for toxic action. GABAergic system has been involved in processes related to the memory formation and consolidation. The present work studied the importance of GABA to the mechanisms involved in the very early development of fipronil-induced memory impairment in rats. Memory behavior was assessed using new object recognition task (ORT) and eight radial arm maze task (8-RAM) to study effects on cognitive and spatial memory. Locomotor behavior was assessed using open field task (OF). The dose of fipronil utilized was studied through a pilot experiment. The GABA antagonist picrotoxin (P) was used to enhance fipronil effects on GABAergic system. Fipronil or picrotoxin decrease memory studied in ORT and 8-RAM tasks. Additionally, F and P co-exposure enhanced effects on memory compared to controls, F, and P, suggesting strongly a GABAergic effect. Weight gain modulation and fipronil in blood were utilized as animal's intoxication indicators. In conclusion, here we report that second-generation pesticides, such as fipronil, can have toxic interactions with the CNS of mammals and lead to memory impairment by modulating the GABAergic system.

  14. Blast exposure and dual sensory impairment: An evidence review and integrated rehabilitation approach

    Directory of Open Access Journals (Sweden)

    Gabrielle H. Saunders, PhD

    2012-10-01

    Full Text Available Combat exposures to blast can result in both peripheral damage to the ears and eyes and central damage to the auditory and visual processing areas in the brain. The functional effects of the latter include visual, auditory, and cognitive processing difficulties that manifest as deficits in attention, memory, and problem solving--symptoms similar to those seen in individuals with visual and auditory processing disorders. Coexisting damage to the auditory and visual system is referred to as dual sensory impairment (DSI. The number of Operation Iraqi Freedom/Operation Enduring Freedom Veterans with DSI is vast; yet currently no established models or guidelines exist for assessment, rehabilitation, or service-delivery practice. In this article, we review the current state of knowledge regarding blast exposure and DSI and outline the many unknowns in this area. Further, we propose a model for clinical assessment and rehabilitation of blast-related DSI that includes development of a coordinated team-based approach to target activity limitations and participation restrictions in order to enhance reintegration, recovery, and quality of life.

  15. Relationship between serum bilirubin, uric acid and cognition impairment in patients with subcortical ischemic vascular disease%皮质下缺血性血管病患者血清胆红素和尿酸水平与认知损害的关系

    Institute of Scientific and Technical Information of China (English)

    周霞; 王龙; 刘寒; 孙中武

    2014-01-01

    acid as well as their relationship with cognitive function in patients with subcortical ischemic vascular disease (SIVD).Methods Serum direct bilirubin (DBIL),indirect bilirubin (IBIL),total bilirubin (TBIL),uric acid (UA) and vascular risk factors were analyzed in 238 individuals comprising 161 patients with SIVD and 77 controls with normal cognitive function.SIVD patients were divided into two subgroups:those with cognitive impairment (SVMCI) and those with dementia (SVaD).All of them were subject to the cognitive assessment including Mini-mental State Examination(MMSE),the Cambridge Cognitive Examination-Chinese Version (CAMCOGC) and Clinical Demential Rating (CDR).Leukoaraiosis was graded according to the severity by their MRI scan appearances.Results MMSE and CAMCOG scores were significant lower in SVMCI and SVaD groups (17.9 ± 5.01,59.87 ± 12.89 ; 24.84 ± 1.57,83.66 ± 4.79) when compared to those in the controls (28.19 ± 1.03,91.66-± 4.93 ; Z =197.63,P =0.000 ; Z =186.54,P =0.000).In comparison with the controls,serum levels of DBIL,IBIL,and TBIL in SVaD group were significant lower ((2.85 ± 1.09) μmol/L vs (3.24 ± 1.30) iμmol/L; (7.50 ±3.27) μmol/L vs (9.06 ±3.52) μmol/L; (10.37 ±4.10) μ mol/L vs (12.31 ±4.64) μmol/L; P =0.035,P =0.005,P =0.006).Also,serum IBIL level was significant lower in SVMCI group compared to the controls ((7.86 ± 3.28) μmol/L vs (9.06 ± 3.52) μmol/L,P =0.034).While serum level of UA was significantly higher in SVMCI ((341.47 ± 92.80) μmol/L) and SVaD ((356.34 ±80.89) μmol/L) groups as compared to those in controls((310.52 ±79.85) μmol/L;P =0.025 ;P =0.001).The UA level was negatively correlated with MMSE scores and CAMCOG-C scores (r =-0.180,P =0.005; r =-0.203,P =0.002),while the bilirubin level was positively correlated with language (r =0.130,P =0.045) and recent memory (r =0.160,P =0.014) scores in CAMCOG-C.The UA level remained associated with MMSE after controlling for age

  16. 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.

  17. Perinatal exposure of mice to the pesticide DDT impairs energy expenditure and metabolism in adult female offspring.

    Science.gov (United States)

    La Merrill, Michele; Karey, Emma; Moshier, Erin; Lindtner, Claudia; La Frano, Michael R; Newman, John W; Buettner, Christoph

    2014-01-01

    Dichlorodiphenyltrichloroethane (DDT) has been used extensively to control malaria, typhus, body lice and bubonic plague worldwide, until countries began restricting its use in the 1970s. Its use in malaria control continues in some countries according to recommendation by the World Health Organization. Individuals exposed to elevated levels of DDT and its metabolite dichlorodiphenyldichloroethylene (DDE) have an increased prevalence of diabetes and insulin resistance. Here we hypothesize that perinatal exposure to DDT disrupts metabolic programming leading to impaired metabolism in adult offspring. To test this, we administered DDT to C57BL/6J mice from gestational day 11.5 to postnatal day 5 and studied their metabolic phenotype at several ages up to nine months. Perinatal DDT exposure reduced core body temperature, impaired cold tolerance, decreased energy expenditure, and produced a transient early-life increase in body fat in female offspring. When challenged with a high fat diet for 12 weeks in adulthood, female offspring perinatally exposed to DDT developed glucose intolerance, hyperinsulinemia, dyslipidemia, and altered bile acid metabolism. Perinatal DDT exposure combined with high fat feeding in adulthood further impaired thermogenesis as evidenced by reductions in core temperature and in the expression of numerous RNA that promote thermogenesis and substrate utilization in the brown adipose tissue of adult female mice. These observations suggest that perinatal DDT exposure impairs thermogenesis and the metabolism of carbohydrates and lipids which may increase susceptibility to the metabolic syndrome in adult female offspring.

  18. Perinatal exposure of mice to the pesticide DDT impairs energy expenditure and metabolism in adult female offspring.

    Directory of Open Access Journals (Sweden)

    Michele La Merrill

    Full Text Available Dichlorodiphenyltrichloroethane (DDT has been used extensively to control malaria, typhus, body lice and bubonic plague worldwide, until countries began restricting its use in the 1970s. Its use in malaria control continues in some countries according to recommendation by the World Health Organization. Individuals exposed to elevated levels of DDT and its metabolite dichlorodiphenyldichloroethylene (DDE have an increased prevalence of diabetes and insulin resistance. Here we hypothesize that perinatal exposure to DDT disrupts metabolic programming leading to impaired metabolism in adult offspring. To test this, we administered DDT to C57BL/6J mice from gestational day 11.5 to postnatal day 5 and studied their metabolic phenotype at several ages up to nine months. Perinatal DDT exposure reduced core body temperature, impaired cold tolerance, decreased energy expenditure, and produced a transient early-life increase in body fat in female offspring. When challenged with a high fat diet for 12 weeks in adulthood, female offspring perinatally exposed to DDT developed glucose intolerance, hyperinsulinemia, dyslipidemia, and altered bile acid metabolism. Perinatal DDT exposure combined with high fat feeding in adulthood further impaired thermogenesis as evidenced by reductions in core temperature and in the expression of numerous RNA that promote thermogenesis and substrate utilization in the brown adipose tissue of adult female mice. These observations suggest that perinatal DDT exposure impairs thermogenesis and the metabolism of carbohydrates and lipids which may increase susceptibility to the metabolic syndrome in adult female offspring.

  19. Inaccurate values for direct bilirubin with some commonly used direct bilirubin procedures.

    Science.gov (United States)

    Chan, K M; Scott, M G; Wu, T W; Clouse, R E; Calvin, D R; Koenig, J; Lichti, D A; Ladenson, J H

    1985-09-01

    We compared five methods for the determination of total and direct bilirubins in serum samples from normal controls, subjects with Gilbert's syndrome, and serum pools containing about 50 and 150 mg of total bilirubin per liter. The Kodak Ektachem method and a diazotized sulfanilic acid method with 0.15 mmol/L sodium nitrite concentrations are the only methods that gave accurate direct bilirubin values, as judged by liquid-chromatographic results. The aca method that involved p-nitrobenzene diazonium tetrafluoroborate and another diazotized sulfanilic acid method with a higher concentration of sodium nitrite (0.8 mmol/L) yielded falsely high values for direct bilirubin, which could lead to clinical confusion. The more recently introduced diazotized sulfanilic acid method of the aca gave substantially better results than the p-nitrobenzene diazonium tetrafluoroborate method but was still inaccurate. Systematic investigation of these procedures revealed that the overestimation of direct bilirubin by the diazotized sulfanilic acid method was related to the amount of unconjugated bilirubin present and its ability to react as direct bilirubin in the presence of higher concentrations of sodium nitrite. Inherent properties of p-nitrobenzene diazonium tetrafluoroborate appeared to be responsible for inaccuracies in that method, which could not be corrected by varying reagent concentration or the reaction conditions.

  20. Impaired acquired resistance of mice to Klebsiella pneumoniae infection induced by acute NO/sub 2/ exposure

    Energy Technology Data Exchange (ETDEWEB)

    Bouley, G.; Azoulay-Dupuis, E.; Gaudebout, C.

    1985-12-01

    The natural resistance of nonimmunized C57B1/6 mice to an intraperitoneal Klebsiella pneumoniae challenge was not significantly affected by prior continuous exposure to 20 ppm NO/sub 2/ for 4 days. In contrast, the acquired resistance of mice immunized just before and infected just after NO/sub 2/ exposure was seriously impaired. This could not be explained by the loss of appetite (about 30%) observed in NO/sub 2/ treated mice, for neither the natural nor acquired resistance of control air exposure mice given approximately 70% ad libitum food and water were significantly modified.

  1. Exposure to 100% Oxygen Abolishes the Impairment of Fracture Healing after Thoracic Trauma.

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    Julia Kemmler

    Full Text Available In polytrauma patients a thoracic trauma is one of the most critical injuries and an important trigger of post-traumatic inflammation. About 50% of patients with thoracic trauma are additionally affected by bone fractures. The risk for fracture malunion is considerably increased in such patients, the pathomechanisms being poorly understood. Thoracic trauma causes regional alveolar hypoxia and, subsequently, hypoxemia, which in turn triggers local and systemic inflammation. Therefore, we aimed to unravel the role of oxygen in impaired bone regeneration after thoracic trauma. We hypothesized that short-term breathing of 100% oxygen in the early post-traumatic phase ameliorates inflammation and improves bone regeneration. Mice underwent a femur osteotomy alone or combined with blunt chest trauma 100% oxygen was administered immediately after trauma for two separate 3 hour intervals. Arterial blood gas tensions, microcirculatory perfusion and oxygenation were assessed at 3, 9 and 24 hours after injury. Inflammatory cytokines and markers of oxidative/nitrosative stress were measured in plasma, lung and fracture hematoma. Bone healing was assessed on day 7, 14 and 21. Thoracic trauma induced pulmonary and systemic inflammation and impaired bone healing. Short-term exposure to 100% oxygen in the acute post-traumatic phase significantly attenuated systemic and local inflammatory responses and improved fracture healing without provoking toxic side effects, suggesting that hyperoxia could induce anti-inflammatory and pro-regenerative effects after severe injury. These results suggest that breathing of 100% oxygen in the acute post-traumatic phase might reduce the risk of poorly healing fractures in severely injured patients.

  2. DEHP exposure impairs mouse oocyte cyst breakdown and primordial follicle assembly through estrogen receptor-dependent and independent mechanisms

    Energy Technology Data Exchange (ETDEWEB)

    Mu, Xinyi [Laboratory of Reproductive Biology, Chongqing Medical University, Chongqing 400016 (China); Department of Histology and Embryology, College of Basic Medicine, Chongqing Medical University, Chongqing 400016 (China); Liao, Xinggui; Chen, Xuemei; Li, Yanli; Wang, Meirong; Shen, Cha; Zhang, Xue; Wang, Yingxiong; Liu, Xueqing [Laboratory of Reproductive Biology, Chongqing Medical University, Chongqing 400016 (China); He, Junlin, E-mail: hejunlin_11@aliyun.com [Laboratory of Reproductive Biology, Chongqing Medical University, Chongqing 400016 (China)

    2015-11-15

    Highlights: • DEHP inhibits primordial folliculogenesis in vivo and in vitro. • Estrogen receptors participate in the effect of DEHP on early ovarian development. • DEHP exposure impairs the expression of Notch2 signaling components. • DEHP exposure disrupts the proliferation of pregranulosa precursor cells. - Abstract: Estrogen plays an essential role in the development of mammalian oocytes, and recent studies suggest that it also regulates primordial follicle assembly in the neonatal ovaries. During the last decade, potential exposure of humans and animals to estrogen-like endocrine disrupting chemicals has become a growing concern. In the present study, we focused on the effect of diethylhexyl phthalate (DEHP), a widespread plasticizer with estrogen-like activity, on germ-cell cyst breakdown and primordial follicle assembly in the early ovarian development of mouse. Neonatal mice injected with DEHP displayed impaired cyst breakdown. Using ovary organ cultures, we revealed that impairment was mediated through estrogen receptors (ERs), as ICI 182,780, an efficient antagonist of ER, reversed this DEHP-mediated effect. DEHP exposure reduced the expression of ERβ, progesterone receptor (PR), and Notch2 signaling components. Finally, DEHP reduced proliferation of pregranulosa precursor cells during the process of primordial folliculogenesis. Together, our results indicate that DEHP influences oocyte cyst breakdown and primordial follicle formation through several mechanisms. Therefore, exposure to estrogen-like chemicals during fetal or neonatal development may adversely influence early ovarian development.

  3. Maternal PTSD following Exposure to the Wenchuan Earthquake Is Associated with Impaired Mental Development of Children

    Science.gov (United States)

    Cai, Dongge; Zhu, Zhongliang; Sun, Hongli; Qi, Yanhua; Xing, Lanying; Zhao, Xiaogui; Wan, Qiuyuan; Su, Qian; Li, Hui

    2017-01-01

    The purpose of this study was to explore whether earthquake-related maternal Post-Traumatic Stress Disorder (PTSD) is associated with impaired development of infants. Participants included 86 women who were pregnant during or after the earthquake in Ningqiang county, and their children. Data were collected from February to March of 2012. PTSD questionnaire (PTSD Checklist, Civilian Version (PCL-C)) was used to measure the effect of the earthquake on mothers, and that the scores greater than 50 were used to indicate presence of PTSD. Each child was assessed using the mental Developmental Screening Test (DST) according to age. Among the 86 women, PTSD scores equal to or greater than 50 accounted for 20.93%. Among the 86 children, 25.60% of development quotient (DQ) scores and 19.80% of mental index (MI) scores were less than 85. The correlation coefficient analysis showed that PTSD scores were inversely related to DQ and MI scores. Maternal PTSD following earthquake exposure is associated with relatively lower intellectual development in children age 0–3 years. Further research is needed to assess the persistent effects of this influence on offspring of mothers exposed to earthquake. PMID:28369095

  4. Hypermethylation of Hippocampal Synaptic Plasticity-Related genes is Involved in Neonatal Sevoflurane Exposure-Induced Cognitive Impairments in Rats.

    Science.gov (United States)

    Ju, Ling-sha; Jia, Min; Sun, Jie; Sun, Xiao-ru; Zhang, Hui; Ji, Mu-huo; Yang, Jian-jun; Wang, Zhong-yun

    2016-02-01

    General anesthetics given to immature rodents cause delayed neurobehavioral abnormalities via incompletely understood mechanisms. DNA methylation, one of the epigenetic modifications, is essential for the modulation of hippocampal synaptic plasticity through regulating the related genes. Therefore, we investigated whether abnormalities in the hippocampal DNA methylation of synaptic plasticity-related genes are involved in neonatal sevoflurane exposure-induced cognitive impairments in rats. Male Sprague-Dawley rats were exposed to 3 % sevoflurane or 30 % oxygen/air for 2 h daily from postnatal day 7 (P7) to P9 and were treated with DNA methyltransferases (DNMTs) inhibitor 5-aza-2-deoxycytidine (5-AZA) or vehicle 1 h before the first sevoflurane exposure on P7. The rats were euthanized 1, 6, 24 h, and 30 days after the last sevoflurane exposure, and the brain tissues were harvested for biochemical analysis. Cognitive functions were evaluated by the open field, fear conditioning, and Morris water maze (MWM) tests on P39, P41-43, and P50-57, respectively. In the present study, repeated neonatal sevoflurane exposure resulted in hippocampus-dependent cognitive impairments as assessed by fear conditioning and MWM tests. The cognitive impairments were associated with the increased DNMTs and hypermethylation of brain-derived neurotrophic factor (BDNF) and Reelin genes, and subsequent down-regulation of BDNF and Reelin genes, which finally led to the decrease of dendritic spines in the hippocampal pyramidal neurons in adolescent rats. Notably, pretreatment with 5-AZA reversed these sevoflurane-induced abnormalities. In conclusion, our results suggest that hypermethylation of hippocampal BDNF and Reelin is involved in neonatal sevoflurane exposure-induced cognitive impairments.

  5. Acute Free-Iron Exposure Does Not Explain the Impaired Haemorheology Associated with Haemochromatosis.

    Directory of Open Access Journals (Sweden)

    Antony P McNamee

    Full Text Available Given the severity of the current imbalance between blood donor supply and recipient demand, discarded blood drawn from the routine venesections of haemochromatosis (HFE-HH patients may serve as a valuable alternative source for blood banks and transfusion. We investigated whether functional or biochemical differences existed between HFE-HH and control blood samples, with particular focus upon the haemorheological properties, to investigate the viability of venesected blood being subsequently harvested for blood products.Blood samples were collected from HFE-HH patients undergoing venesection treatment (n = 19 and healthy volunteers (n = 8. Moreover, a second experiment investigated the effects of a dose-response of iron (0, 40, 80, 320 mM FeCl3 on haemorheology in healthy blood samples (n = 7. Dependent variables included basic haematology, iron status, haematocrit, red blood cell (RBC aggregation (native and standardised haematocrit and "aggregability" (RBC tendency to aggregate in a standard aggregating medium; 0.4 L/L haematocrit in a Dx70, and RBC deformability.Indices of RBC deformability were significantly decreased for HFE-HH when compared with healthy controls: RBC deformability was significantly decreased at 1-7 Pa (p < 0.05, and the shear stress required for half maximal deformability was significantly increased (p < 0.05 for HFE-HH. RBC aggregation in plasma was significantly increased (p < 0.001 for HFE-HH, although when RBC were suspended in plasma-free Dx70 no differences were detected. No differences in RBC deformability or RBC aggregation/aggregability were detected when healthy RBC were incubated with varying dose of FeCl3.HFE-HH impairs the haemorheological properties of blood; however, RBC aggregability was similar between HFE-HH and controls when cells were suspended in a plasma-free medium, indicating that plasma factor(s may explain the altered haemorheology in HFE-HH patients. Acute exposure to elevated iron levels does

  6. Exposure to a Low Lead Concentration Impairs Contractile Machinery in Rat Cardiac Muscle.

    Science.gov (United States)

    Silva, Marito A S C; de Oliveira, Thiago F; Almenara, Camila C P; Broseghini-Filho, Gilson B; Vassallo, Dalton V; Padilha, Alessandra S; Silveira, Edna A

    2015-10-01

    Lead exposure has been considered to be a risk factor for hypertension and cardiovascular disease. Our purpose was to evaluate the effects of low plasma lead concentration on cardiac contractility in isolated papillary muscles. Wistar rats were divided in control group or group treated with 100 ppm of lead acetate in the drinking water for 15 days. Blood pressure (BP) was measured weekly. At the end of the treatment period, the animals were anesthetized and euthanized, and parameters related to isolated papillary muscle contractility were recorded. The lead concentrations in the blood reached 12.3 ± 2 μg/dL. The BP was increased in the group treated with 100 ppm of lead acetate. Lead treatment did not alter force and time derivatives of the force of left ventricular papillary muscles. In addition, the inotropic response induced by an increase in the extracellular Ca(2+) concentration was reduced in the Pb(2+) group. However, the uptake of Ca(2+) by the sarcoplasmic reticulum and the protein expression of SERCA and phospholamban remained unchanged. Postrest contraction was similar in the both groups, and tetanic peak and plateau tension were reduced in lead group. These results demonstrated that the reduction in the inotropic response to calcium does not appear to be caused by changes in the trans-sarcolemmal calcium flux but suggest that an impairment of the contractile machinery might be taking place. Our results demonstrate that even at a concentration below the limit considered to be safe, lead exerts deleterious effects on the cardiac contractile machinery.

  7. In vitro exposure of human fibroblasts to local anaesthetics impairs cell growth

    Science.gov (United States)

    Fedder, C; Beck-Schimmer, B; Aguirre, J; Hasler, M; Roth-Z'graggen, B; Urner, M; Kalberer, S; Schlicker, A; Votta-Velis, G; Bonvini, J M; Graetz, K; Borgeat, A

    2010-01-01

    Lidocaine, bupivacaine or ropivacaine are used routinely to manage perioperative pain. Sparse data exist evaluating the effects of local anaesthetics (LA) on fibroblasts, which are involved actively in wound healing. Therefore, we investigated the effects of the three LA to assess the survival, viability and proliferation rate of fibroblasts. Human fibroblasts were exposed to 0·3 mg/ml and 0·6 mg/ml of each LA for 2 days, followed by incubation with normal medium for another 1, 4 or 7 days (group 1). Alternatively, cells were incubated permanently with LA for 3, 6 or 9 days (group 2). Live cell count was assessed using trypan blue staining. Viability was measured by the tetrazolium bromide assay. Proliferation tests were performed with the help of the colorimetric bromodeoxyuridine assay. Production of reactive oxygen species (ROS) was determined, measuring the oxidation of non-fluorescent-2,7′-dichlorofluorescin. Treatment of cells with the three LA showed a concentration-dependent decrease of live cells, mitochondrial activity and proliferation rate. Group arrangement played a significant role for cell count and proliferation, while exposure time influenced viability. Among the analysed LA, bupivacaine showed the most severe cytotoxic effects. Increased production of ROS correlated with decreased viability of fibroblasts in lidocaine- and bupivacaine-exposed cells, but not upon stimulation with ropivacaine. This study shows a concentration-dependent cytotoxic effect of lidocaine, bupivacaine and ropivacaine on fibroblasts in vitro, with more pronounced effects after continuous incubation. A possible mechanism of cell impairment could be triggered by production of ROS upon stimulation with lidocaine and bupivacaine. PMID:20819090

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

    Science.gov (United States)

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

    2008-05-01

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

  9. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) increases bilirubin formation but hampers quantitative hepatic conversion of biliverdin to bilirubin in rats with wild-type AH receptor.

    Science.gov (United States)

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

    2014-06-01

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

  10. Chronic Exposure to Water-Pipe Smoke Induces Alveolar Enlargement, DNA Damage and Impairment of Lung Function

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    Abderrahim Nemmar

    2016-03-01

    Full Text Available Background/Aim: Epidemiological evidence indicates that water-pipe smoking (WPS adversely affects the respiratory system. However, the mechanisms underlying its effects are not well understood. Recent experimental studies reported the occurrence of lung inflammation and oxidative stress following acute and subacute exposure to WPS. Here, we wanted to verify the extent of inflammation and oxidative stress in mice chronically-exposed to WPS and to evaluate, for the first time, its effect on alveolar injury and DNA damage and their association with impairment of lung function. Methods: Mice were nose-only exposed to mainstream WPS (30 min/day; 5 days/week for 6 consecutive months. Control mice were exposed using the same protocol to atmospheric air only. At the end of the exposure period, several respiratory parameters were assessed. Results: In bronchoalveolar lavage fluid, WPS increased neutrophil and lymphocyte numbers, lactate dehydrogenase, myeloperoxidase and matrix metallopeptidase 9 activities, as well as several proinflammatory cytokines. In lung tissue, lipid peroxidation, reactive oxygen species, superoxide dismutase activity and reduced glutathione were all increased by WPS exposure. Along with oxidative stress, WPS exposure significantly increased lung DNA damage index. Histologically the lungs of WPS-exposed mice had foci of mixed inflammatory cells infiltration in the interalveolar interstitium which consisted of neutrophils, lymphocytes and macrophages. Interestingly, we found dilated alveolar spaces and alveolar ducts with damaged interalveolar septae, and impairment of lung function following WPS exposure. Conclusion: We show the persistence of lung inflammation and oxidative stress in mice chronically-exposed to WPS and demonstrate, for the first time, the occurrence of DNA damage and enlargement of alveolar spaces and ducts associated with impairment of lung function. Our findings provide novel mechanistic elucidation for the

  11. BILIRUBIN AS AN INDIRECT MEASURE OF LABORATORY PERFORMANCE OF BILIRUBIN DETERMINATIONS

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    Suresh Babu

    2015-09-01

    Full Text Available OBJECTIVE : To correlate Total Serum Bilirubin (TSB values to the clinical course of hyperbilirubinemia in newborns as this can be an indirect method of quality assurance in the laboratory. METHODS : An observational study of bilirubin values from 100 randomly selected case records of newborn jaundice for a period of 6 months. TSB values were determined by diazo reaction on venous blood samples on a semi auto analyzer. MS excel sheet used for statistical analysis. RESULTS : Clinical course of hyperbilirubinemia in all subjects correlated well to the reported TSB values in first to last zones corresponding to 15 mg /dL on 3rd day to 5th day of age. Zones 3, 4 and 5 varied from 7th day of birth, as phototherapy and recovery altered visual assessment of jaundice. One patient was expired with kernicterus had very high TSB value. The median bilirubin values trend downfall which correlated clinically to recovery from jaundice and 33% rapid decline in TSB also indicated the intervention by phototherapy. CONCLUSIONS : Bilirubin is one parameter with higher inter laboratory variability since its discovery till today. Hence more quality methods are to be developed to minimize this bias in clinical interpretation of reported bilirubin levels. Our study is an intermediary quality measure useful for both clinicians and lab personnel. This study can be adopted for retrospective quality evaluation and can be adopted for other parameters as well.

  12. Docosahexaenoic Acid Rescues Synaptogenesis Impairment and Long-Term Memory Deficits Caused by Postnatal Multiple Sevoflurane Exposures

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    Guorong Tao

    2016-01-01

    Full Text Available Sevoflurane exposures were demonstrated to induce neurotoxicity in the developing brain in both human and animal studies. However, there is no effective approach to reverse it. The present study aimed to evaluate the feasibility of utilizing docosahexaenoic acid (DHA to prevent sevoflurane-induced neurotoxicity. P6 (postnatal 6 days mice were administrated DHA after exposure to 3% sevoflurane for two hours daily in three consecutive days. Molecular expressions of synaptic makers (PSD95, synaptophysin and synaptic morphological changes were investigated by Western blot analysis and transmission electron microscopy, respectively. Meanwhile, Morris water maze test was used to assess spatial memory of mice at P31 (postnatal 31 days. DHA restored sevoflurane-induced decreased level of PSD95 and synaptophysin expressions and increased PSD areas and also improved long-term spatial memory. These results suggest that DHA could rescue synaptogenesis impairment and long-term memory deficits in postnatal caused by multiple sevoflurane exposures.

  13. 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...

  14. Ethanol exposure during the early first trimester equivalent impairs reflexive motor activity and heightens fearfulness in an avian model.

    Science.gov (United States)

    Smith, Susan M; Flentke, George R; Kragtorp, Katherine A; Tessmer, Laura

    2011-02-01

    Prenatal alcohol exposure is a leading cause of childhood neurodevelopmental disability. The adverse behavioral effects of alcohol exposure during the second and third trimester are well documented; less clear is whether early first trimester-equivalent exposures also alter behavior. We investigated this question using an established chick model of alcohol exposure. In ovo embryos experienced a single, acute ethanol exposure that spanned gastrulation through neuroectoderm induction and early brain patterning (19-22h incubation). At 7 days posthatch, the chicks were evaluated for reflexive motor function (wingflap extension, righting reflex), fearfulness (tonic immobility [TI]), and fear/social reinstatement (open-field behavior). Chicks exposed to a peak ethanol level of 0.23-0.28% were compared against untreated and saline-treated controls. Birds receiving early ethanol exposure had a normal righting reflex and a significantly reduced wingflap extension in response to a sudden descent. The ethanol-treated chicks also displayed heightened fearfulness, reflected in increased frequency of TI, and they required significantly fewer trials for its induction. In an open-field test, ethanol treatment did not affect latency to move, steps taken, vocalizations, defecations, or escape attempts. The current findings demonstrate that early ethanol exposure can increase fearfulness and impair aspects of motor function. Importantly, the observed dysfunctions resulted from an acute ethanol exposure during the period when the major brain components are induced and patterned. The equivalent period in human development is 3-4 weeks postconception. The current findings emphasize that ethanol exposure during the early first trimester equivalent can produce neurodevelopmental disability in the offspring.

  15. Exposure to electronic cigarettes impairs pulmonary anti-bacterial and anti-viral defenses in a mouse model.

    Directory of Open Access Journals (Sweden)

    Thomas E Sussan

    Full Text Available Electronic cigarettes (E-cigs have experienced sharp increases in popularity over the past five years due to many factors, including aggressive marketing, increased restrictions on conventional cigarettes, and a perception that E-cigs are healthy alternatives to cigarettes. Despite this perception, studies on health effects in humans are extremely limited and in vivo animal models have not been generated. Presently, we determined that E-cig vapor contains 7 x 10(11 free radicals per puff. To determine whether E-cig exposure impacts pulmonary responses in mice, we developed an inhalation chamber for E-cig exposure. Mice that were exposed to E-cig vapor contained serum cotinine concentrations that are comparable to human E-cig users. E-cig exposure for 2 weeks produced a significant increase in oxidative stress and moderate macrophage-mediated inflammation. Since, COPD patients are susceptible to bacterial and viral infections, we tested effects of E-cigs on immune response. Mice that were exposed to E-cig vapor showed significantly impaired pulmonary bacterial clearance, compared to air-exposed mice, following an intranasal infection with Streptococcus pneumonia. This defective bacterial clearance was partially due to reduced phagocytosis by alveolar macrophages from E-cig exposed mice. In response to Influenza A virus infection, E-cig exposed mice displayed increased lung viral titers and enhanced virus-induced illness and mortality. In summary, this study reports a murine model of E-cig exposure and demonstrates that E-cig exposure elicits impaired pulmonary anti-microbial defenses. Hence, E-cig exposure as an alternative to cigarette smoking must be rigorously tested in users for their effects on immune response and susceptibility to bacterial and viral infections.

  16. Exposure to electronic cigarettes impairs pulmonary anti-bacterial and anti-viral defenses in a mouse model.

    Science.gov (United States)

    Sussan, Thomas E; Gajghate, Sachin; Thimmulappa, Rajesh K; Ma, Jinfang; Kim, Jung-Hyun; Sudini, Kuladeep; Consolini, Nicola; Cormier, Stephania A; Lomnicki, Slawo; Hasan, Farhana; Pekosz, Andrew; Biswal, Shyam

    2015-01-01

    Electronic cigarettes (E-cigs) have experienced sharp increases in popularity over the past five years due to many factors, including aggressive marketing, increased restrictions on conventional cigarettes, and a perception that E-cigs are healthy alternatives to cigarettes. Despite this perception, studies on health effects in humans are extremely limited and in vivo animal models have not been generated. Presently, we determined that E-cig vapor contains 7 x 10(11) free radicals per puff. To determine whether E-cig exposure impacts pulmonary responses in mice, we developed an inhalation chamber for E-cig exposure. Mice that were exposed to E-cig vapor contained serum cotinine concentrations that are comparable to human E-cig users. E-cig exposure for 2 weeks produced a significant increase in oxidative stress and moderate macrophage-mediated inflammation. Since, COPD patients are susceptible to bacterial and viral infections, we tested effects of E-cigs on immune response. Mice that were exposed to E-cig vapor showed significantly impaired pulmonary bacterial clearance, compared to air-exposed mice, following an intranasal infection with Streptococcus pneumonia. This defective bacterial clearance was partially due to reduced phagocytosis by alveolar macrophages from E-cig exposed mice. In response to Influenza A virus infection, E-cig exposed mice displayed increased lung viral titers and enhanced virus-induced illness and mortality. In summary, this study reports a murine model of E-cig exposure and demonstrates that E-cig exposure elicits impaired pulmonary anti-microbial defenses. Hence, E-cig exposure as an alternative to cigarette smoking must be rigorously tested in users for their effects on immune response and susceptibility to bacterial and viral infections.

  17. Chronic exposure to bisphenol a impairs progesterone receptor-mediated signaling in the uterus during early pregnancy

    Science.gov (United States)

    Li, Quanxi; Davila, Juanmahel; Bagchi, Milan K.; Bagchi, Indrani C.

    2016-01-01

    Environmental and occupational exposure to endocrine disrupting chemicals (EDCs) is a major threat to female reproductive health. Bisphenol A (BPA), an environmental toxicant that is commonly found in polycarbonate plastics and epoxy resins, has received much attention due to its estrogenic activity and high risk of chronic exposure in human. Whereas BPA has been linked to infertility and recurrent miscarriage in women, the impact of its exposure on uterine function during early pregnancy remains unclear. In a recent publication in Endocrinology, we demonstrated that prolonged exposure to an environmental relevant dose of BPA disrupts progesterone receptor-regulated uterine functions, thus affecting uterine receptivity for embryo implantation and decidua morphogenesis, two critical events for establishment and maintenance of early pregnancy. In particular we reported a marked impairment of progesterone receptor (PGR) expression and its downstream effector HAND2 in the uterine stromal cells in response to chronic BPA exposure. In an earlier study we have shown that HAND2 controls embryo implantation by repressing fibroblast growth factor (FGF) expression and the MAP kinase signaling pathway, thus inhibiting epithelial proliferation. Interestingly we observed that downregulation of PGR and HAND2 expression in uterine stroma upon BPA exposure was associated with an enhanced activation of FGFR and MAPK signaling, aberrant proliferation, and lack of uterine receptivity in the epithelium. In addition, the proliferation and differentiation of endometrial stromal cells to decidual cells, an event critical for the maintenance of early pregnancy, was severely compromised in response to BPA. This research highlight will provide an overview of our findings and discuss the potential mechanisms by which chronic BPA impairs PGR-HAND2 pathway and adversely affects implantation and the establishment of pregnancy.

  18. Neurological effects of inorganic arsenic exposure: altered cysteine/glutamate transport, NMDA expression and spatial memory impairment.

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    Lucio A Ramos-Chávez

    2015-02-01

    Full Text Available Inorganic arsenic (iAs is an important natural pollutant. Millions of individuals worldwide drink water with high levels of iAs. Chronic exposure to iAs has been associated with lower IQ and learning disabilities as well as memory impairment. iAs is methylated in tissues such as the brain generating mono and dimethylated species. iAs methylation requires cellular glutathione (GSH, which is the main antioxidant in the central nervous system. In humans, As species cross the placenta and are found in cord blood. A CD1 mouse model was used to investigate effects of gestational iAs exposure which can lead to oxidative damage, disrupted cysteine/glutamate transport and its putative impact in learning and memory. On postnatal days (PNDs 1, 15 and 90, the expression of membrane transporters related to GSH synthesis and glutamate transport and toxicity, such as xCT, EAAC1, GLAST and GLT1, as well as LAT1, were analyzed. Also, the expression of the glutamate receptor N-methyl-D-aspartate (NMDAR subunits NR2A and B as well as the presence of As species in cortex and hippocampus were investigated. On PND 90, an object location task was performed to associate exposure with memory impairment. Gestational exposure to iAs affected the expression of cysteine/glutamate transporters in cortex and hippocampus and induced a negative modulation of NMDAR NR2B subunit in the hippocampus. Behavioral tasks showed significant spatial memory impairment in males while the effect was marginal in females.

  19. Impairment of social behaviour persists two years after embryonic alcohol exposure in zebrafish: A model of fetal alcohol spectrum disorders.

    Science.gov (United States)

    Fernandes, Yohaan; Rampersad, Mindy; Gerlai, Robert

    2015-10-01

    Zebrafish naturally form social groups called shoals. Previously, we have shown that submerging zebrafish eggs into low concentrations of alcohol (0.00, 0.25, 0.50, 0.75 and 1.00 vol/vol% external bath concentration) during development (24h post-fertilization) for two hours resulted in impaired shoaling response in seven month old young adult zebrafish. Here we investigate whether this embryonic alcohol exposure induced behavioural deficit persists to older age. Zebrafish embryos were exposed either to fresh system water (control) or to 1% alcohol for two hours, 24h after fertilization, and were raised in a high-density tank system. Social behaviour was tested by presenting the experimental fish with a computer animated group of zebrafish images, while automated tracking software measured their behaviour. Control fish were found to respond strongly to animated conspecific images by reducing their distanceand remaining close to the images during image presentation, embryonic alcohol treated fish did not. Our results suggest that the impaired shoaling response of the alcohol exposed fish was not due to altered motor function or visual perception, but likely to a central nervous system alteration affecting social behaviour itself. We found the effects of embryonic alcohol exposure on social behaviour not to diminish with age, a result that demonstrates the deleterious and potentially life-long consequences of exposure to even small amount of alcohol during embryonic development in vertebrates.

  20. Cigarette smoke impairs granulosa cell proliferation and oocyte growth after exposure cessation in young Swiss mice: an experimental study

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    Paixão Larissa LO

    2012-09-01

    Full Text Available Abstract Background Cigarette smoke is associated with decreased female fertility, causing damage to ovarian function and disturbing follicle development. However, the effects of cigarette toxicants on ovarian function depend on duration and intensity of exposure. The aim of this study was to assess the effects of brief, intense exposure to tobacco smoke on granulosa cell number, oocyte growth, and follicle size during puberty in female Swiss mice. Methods Ten female Swiss mice aged 35 days were exposed to tobacco smoke from 3R4F reference research cigarettes. They were exposed to an automatic smoking machine 8 h/day, 7 days/week for 15 days. Ten age-matched controls were kept in a different room and exposed to ambient air. At the end of 15 days, five mice in each group were euthanized and the ovaries were analyzed for follicular morphometry and granulosa cell count. The remaining animals were kept for an additional 30 days for further analysis as an ex-smoker group and control group. Comparison between the two groups was evaluated by the Student’s t-test or a two-way ANOVA followed by Bonferroni post-test was applied for multiple comparisons. Results We found that cigarette smoke impaired antral follicular growth even after exposure cessation (p Conclusions The negative effects of cigarette smoking seem to last even after exposure has been interrupted. Moreover, brief exposure during puberty may induce silent oocyte disruption, which could in turn lead to decreased fecundity rates.

  1. Low dose prenatal alcohol exposure does not impair spatial learning and memory in two tests in adult and aged rats.

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    Carlie L Cullen

    Full Text Available Consumption of alcohol during pregnancy can have detrimental impacts on the developing hippocampus, which can lead to deficits in learning and memory function. Although high levels of alcohol exposure can lead to severe deficits, there is a lack of research examining the effects of low levels of exposure. This study used a rat model to determine if prenatal exposure to chronic low dose ethanol would result in deficits in learning and memory performance and if this was associated with morphological changes within the hippocampus. Sprague Dawley rats were fed a liquid diet containing 6% (vol/vol ethanol (EtOH or an isocaloric control diet throughout gestation. Male and Female offspring underwent behavioural testing at 8 (Adult or 15 months (Aged of age. Brains from these animals were collected for stereological analysis of pyramidal neuron number and dendritic morphology within the CA1 and CA3 regions of the dorsal hippocampus. Prenatal ethanol exposed animals did not differ in spatial learning or memory performance in the Morris water maze or Y maze tasks compared to Control offspring. There was no effect of prenatal ethanol exposure on pyramidal cell number or density within the dorsal hippocampus. Overall, this study indicates that chronic low dose prenatal ethanol exposure in this model does not have long term detrimental effects on pyramidal cells within the dorsal hippocampus or impair spatial learning and memory performance.

  2. Orlistat treatment increases fecal bilirubin excretion and decreases plasma bilirubin concentrations in hyperbilirubinemic Gunn rats

    NARCIS (Netherlands)

    Nishioka, T; Hafkamp, AM; Havinga, R; Van Lierop, PPE; Velvis, H; Verkade, HJ

    2003-01-01

    Objective To determine whether serum levels of unconjugated bilirubin (UCB) can be decreased by enhancing fecal fat excretion. Study design Gunn rats were fed a high-fat diet (control) or the same diet mixed with the lipase inhibitor orlistat. At regular intervals, plasma UCB concentrations were det

  3. ANG-(1–7) DEFICIENCY AND BAROREFLEX IMPAIRMENT PRECEDE THE ANTENATAL BETAMETHASONE EXPOSURE-INDUCED ELEVATION IN BLOOD PRESSURE

    Science.gov (United States)

    Shaltout, Hossam A.; Rose, James C.; Chappell, Mark C.; Diz, Debra I.

    2014-01-01

    Betamethasone is administered to accelerate lung development and improve survival of premature infants, but may be associated with hypertension later in life. In a sheep model of fetal programming resulting from exposure at 80th day of gestation to Betamethasone (Betaexposed), adult sheep at 6–9 months or 1.8 yrs of age have elevated mean arterial pressure (MAP), and attenuated spontaneous baroreflex sensitivity (sBRS) for control of heart rate compared to age-matched controls, associated with imbalances in angiotensin (Ang) II versus Ang-(1–7) tone. At 6 weeks of age, evoked BRS is already low in the Beta-exposed animals. In this study we assessed the potential contribution of the renin-angiotensin system to the impaired sBRS. Female lambs (6 weeks old) with Beta-exposure in utero had similar MAP to control lambs (78±2 vs 77±2 mm Hg, n = 4–5 per group), but lower sBRS (8±1 vs 16±3 ms/mm Hg; p < 0.05) and impaired heart rate variability (HRV). Peripheral AT1 receptor blockade using candesartan lowered MAP in both groups (~10 mm Hg) and improved sBRS and HRV in Beta-exposed lambs to a level similar to control. AT7 receptor blockade by infusion of D-ala Ang-(1–7) (700 ng/kg/min for 45 min) reduced sBRS 46±10 % in Beta-exposed vs in control lambs (p<0.15) and increased MAP in both groups (~6±2 mm Hg). Our data reveal that Beta-exposure impairs sBRS and HRV at a time point preceding the elevation in MAP via mechanisms involving an imbalance in the Ang II/Ang-(1–7) ratio consistent with a progressive loss in Ang-(1–7) function. PMID:22215705

  4. Angiotensin-(1-7) deficiency and baroreflex impairment precede the antenatal Betamethasone exposure-induced elevation in blood pressure.

    Science.gov (United States)

    Shaltout, Hossam A; Rose, James C; Chappell, Mark C; Diz, Debra I

    2012-02-01

    Betamethasone is administered to accelerate lung development and improve survival of premature infants but may be associated with hypertension later in life. In a sheep model of fetal programming resulting from exposure at day 80 of gestation to Betamethasone (Beta-exposed), adult sheep at 6 to 9 months or 1.8 years of age have elevated mean arterial pressure (MAP) and attenuated spontaneous baroreflex sensitivity (sBRS) for control of heart rate compared to age-matched controls associated with imbalances in angiotensin (Ang) II vs Ang-(1-7) tone. At 6 weeks of age, evoked BRS is already low in the Beta-exposed animals. In this study, we assessed the potential contribution of the renin-angiotensin system to the impaired sBRS. Female lambs (6 weeks old) with Beta exposure in utero had similar MAP to control lambs (78±2 vs 77±2 mm Hg, n=4-5 per group), but lower sBRS (8±1 vs 16±3 ms/mm Hg; P<0.05) and impaired heart rate variability. Peripheral AT1 receptor blockade using candesartan lowered MAP in both groups (≈10 mm Hg) and improved sBRS and heart rate variability in Beta-exposed lambs to a level similar to control. AT7 receptor blockade by infusion of D-ala Ang-(1-7) (700 ng/kg/min for 45 minutes) reduced sBRS 46%±10% in Beta-exposed vs in control lambs (P<0.15) and increased MAP in both groups (≈6±2 mm Hg). Our data reveal that Beta exposure impairs sBRS and heart rate variability at a time point preceding the elevation in MAP via mechanisms involving an imbalance in the Ang II/Ang-(1-7) ratio consistent with a progressive loss in Ang-(1-7) function.

  5. Ketogenic diet improves the spatial memory impairment caused by exposure to hypobaric hypoxia through increased acetylation of histones in rats

    Science.gov (United States)

    Zhao, Ming; Huang, Xin; Cheng, Xiang; Lin, Xiao; Zhao, Tong; Wu, Liying; Yu, Xiaodan; Wu, Kuiwu; Fan, Ming

    2017-01-01

    Exposure to hypobaric hypoxia causes neuron cell damage, resulting in impaired cognitive function. Effective interventions to antagonize hypobaric hypoxia-induced memory impairment are in urgent need. Ketogenic diet (KD) has been successfully used to treat drug-resistant epilepsy and improves cognitive behaviors in epilepsy patients and other pathophysiological animal models. In the present study, we aimed to explore the potential beneficial effects of a KD on memory impairment caused by hypobaric hypoxia and the underlying possible mechanisms. We showed that the KD recipe used was ketogenic and increased plasma levels of ketone bodies, especially β-hydroxybutyrate. The results of the behavior tests showed that the KD did not affect general locomotor activity but obviously promoted spatial learning. Moreover, the KD significantly improved the spatial memory impairment caused by hypobaric hypoxia (simulated altitude of 6000 m, 24 h). In addition, the improving-effect of KD was mimicked by intraperitoneal injection of BHB. The western blot and immunohistochemistry results showed that KD treatment not only increased the acetylated levels of histone H3 and histone H4 compared to that of the control group but also antagonized the decrease in the acetylated histone H3 and H4 when exposed to hypobaric hypoxia. Furthermore, KD-hypoxia treatment also promoted PKA/CREB activation and BDNF protein expression compared to the effects of hypoxia alone. These results demonstrated that KD is a promising strategy to improve spatial memory impairment caused by hypobaric hypoxia, in which increased modification of histone acetylation plays an important role. PMID:28355243

  6. Bilirubin dosage in cord blood: could it predict neonatal hyperbilirubinemia?

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    Adélia Jeha Nasser Bernaldo

    Full Text Available CONTEXT: With early discharge, many newborns have to be readmitted to hospital for hyperbilirubinemia to be treated, and this has been held responsible for the reappearance of kernicterus. OBJECTIVE: To evaluate whether bilirubin levels in cord blood could predict neonatal hyperbilirubinemia that would require treatment, in full-term newborns up to their third day of life. TYPE OF STUDY: Prospective study. SETTING: Neonatal Unit of Hospital Israelita Albert Einstein, São Paulo, Brazil. PARTICIPANTS: 380 full-term newborns considered normal: with or without ABO/Rh blood group incompatibility and without other complications. PROCEDURES: Blood was taken from the umbilical cord for analysis of conjugated, unconjugated and total bilirubin serum levels. The newborns were followed up until discharge, and unconjugated bilirubin that required phototherapy was compared to the cord bilirubin assay. Discriminant analysis was used to classify newborns: with or without risk of needing phototherapy by the third day of life. MAIN MEASUREMENTS: Bilirubin assay in cord blood; mother's and newborn's blood groups; phototherapy indication. RESULTS: The mean value for unconjugated bilirubin in cord blood was significantly higher in newborns whose unconjugated bilirubin required phototherapy. The presence of ABO blood group incompatibility was a significant variable in relation to unconjugated bilirubin that required phototherapy. The most useful cutoff point for unconjugated bilirubin in cord blood was 2.0 mg/100 ml. DISCUSSION: Cord blood could be collected, stored and used for further analysis of unconjugated bilirubin levels as a means for considering whether or not to discharge a moderately jaundiced child from hospital, in association with other resources. CONCLUSIONS: Blood incompatibility between mother and child was a predictor for the appearance of hyperbilirubinemia that required treatment. Considering a cutoff point of 2.0 mg/100 ml, it could be concluded

  7. Fetal alcohol exposure leads to abnormal olfactory bulb development and impaired odor discrimination in adult mice

    NARCIS (Netherlands)

    K.G. Akers (Katherine); S.A. Kushner (Steven); A.T. Leslie (Ana); L. Clarke (Laura); D. van der Kooy (Derek); J.P. Lerch (Jason); P.W. Frankland (Paul)

    2011-01-01

    textabstractBackground: Children whose mothers consumed alcohol during pregnancy exhibit widespread brain abnormalities and a complex array of behavioral disturbances. Here, we used a mouse model of fetal alcohol exposure to investigate relationships between brain abnormalities and specific behavior

  8. Early developmental bisphenol-A exposure sex-independently impairs spatial memory by remodeling hippocampal dendritic architecture and synaptic transmission in rats

    Science.gov (United States)

    Liu, Zhi-Hua; Ding, Jin-Jun; Yang, Qian-Qian; Song, Hua-Zeng; Chen, Xiang-Tao; Xu, Yi; Xiao, Gui-Ran; Wang, Hui-Li

    2016-08-01

    Bisphenol-A (BPA, 4, 4‧-isopropylidene-2-diphenol), a synthetic xenoestrogen that widely used in the production of polycarbonate plastics, has been reported to impair hippocampal development and function. Our previous study has shown that BPA exposure impairs Sprague-Dawley (SD) male hippocampal dendritic spine outgrowth. In this study, the sex-effect of chronic BPA exposure on spatial memory in SD male and female rats and the related synaptic mechanism were further investigated. We found that chronic BPA exposure impaired spatial memory in both SD male and female rats, suggesting a dysfunction of hippocampus without gender-specific effect. Further investigation indicated that BPA exposure causes significant impairment of dendrite and spine structure, manifested as decreased dendritic complexity, dendritic spine density and percentage of mushroom shaped spines in hippocampal CA1 and dentate gyrus (DG) neurons. Furthermore, a significant reduction in Arc expression was detected upon BPA exposure. Strikingly, BPA exposure significantly increased the mIPSC amplitude without altering the mEPSC amplitude or frequency, accompanied by increased GABAARβ2/3 on postsynaptic membrane in cultured CA1 neurons. In summary, our study indicated that Arc, together with the increased surface GABAARβ2/3, contributed to BPA induced spatial memory deficits, providing a novel molecular basis for BPA achieved brain impairment.

  9. Early developmental bisphenol-A exposure sex-independently impairs spatial memory by remodeling hippocampal dendritic architecture and synaptic transmission in rats.

    Science.gov (United States)

    Liu, Zhi-Hua; Ding, Jin-Jun; Yang, Qian-Qian; Song, Hua-Zeng; Chen, Xiang-Tao; Xu, Yi; Xiao, Gui-Ran; Wang, Hui-Li

    2016-08-31

    Bisphenol-A (BPA, 4, 4'-isopropylidene-2-diphenol), a synthetic xenoestrogen that widely used in the production of polycarbonate plastics, has been reported to impair hippocampal development and function. Our previous study has shown that BPA exposure impairs Sprague-Dawley (SD) male hippocampal dendritic spine outgrowth. In this study, the sex-effect of chronic BPA exposure on spatial memory in SD male and female rats and the related synaptic mechanism were further investigated. We found that chronic BPA exposure impaired spatial memory in both SD male and female rats, suggesting a dysfunction of hippocampus without gender-specific effect. Further investigation indicated that BPA exposure causes significant impairment of dendrite and spine structure, manifested as decreased dendritic complexity, dendritic spine density and percentage of mushroom shaped spines in hippocampal CA1 and dentate gyrus (DG) neurons. Furthermore, a significant reduction in Arc expression was detected upon BPA exposure. Strikingly, BPA exposure significantly increased the mIPSC amplitude without altering the mEPSC amplitude or frequency, accompanied by increased GABAARβ2/3 on postsynaptic membrane in cultured CA1 neurons. In summary, our study indicated that Arc, together with the increased surface GABAARβ2/3, contributed to BPA induced spatial memory deficits, providing a novel molecular basis for BPA achieved brain impairment.

  10. Impairment of the reproductive potential of male fathead minnows by environmentally relevant exposures to 4-nonylphenolf

    Science.gov (United States)

    Schoenfuss, H.L.; Bartell, S.E.; Bistodeau, T.B.; Cediel, R.A.; Grove, K.J.; Zintek, L.; Lee, K.E.; Barber, L.B.

    2008-01-01

    The synthetic organic compound 4-nonylphenol (NP) has been detected in many human-impacted surface waters in North America. In this study, we examined the ability of NP to alter reproductive competence in male fathead minnows after a 28 day flow-through exposure in a range of environmentally relevant concentrations bracketing the U.S. Environmental Protection Agency toxicity-based NP chronic exposure criterion of 6.1 ??g NP/L. Exposure to NP at and above the EPA chronic exposure criterion resulted in an induction of plasma vitellogenin (VTG) within 14 days. However, 7 days after the cessation of exposure, VTG concentrations had dropped more than 50% and few males expressed VTG above the detection threshold. All of the morphological endpoints, including gonadosomatic index, hepatosomatic index, secondary sexual characters, and histopathology, were unaltered by all NP treatments. However, when NP-exposed male fish were allowed to compete with control males for access to nest sites and females, most treatments altered the reproductive competence of exposed males. At lower NP concentrations, exposed males out-competed control males, possibly by being primed through the estrogenic NP exposure in a fashion similar to priming by pheromones released from female fathead minnows. At higher NP exposure concentrations, this priming effect was negated by the adverse effects of the exposure and control males out-competed treated males. Results of this study indicate the complexity of endocrine disrupting effects and the need for multiple analysis levels to assess the effects of these compounds on aquatic organisms. ?? 2007 Elsevier B.V. All rights reserved.

  11. Short-term exposure of zebrafish embryos to arecoline leads to retarded growth, motor impairment, and somite muscle fiber changes.

    Science.gov (United States)

    Peng, Wei-Hau; Lee, Yen-Chia; Chau, Yat-Pang; Lu, Kuo-Shyan; Kung, Hsiu-Ni

    2015-02-01

    The areca nut-chewing habit is common in Southeast Asia, India, and Taiwan, and arecoline is the most abundant and potent component in the areca nut. The effects of arecoline on birth defects have been explored in many species, including chicken, mice, and zebrafish. The effects of arecoline on embryos after long-term exposure are well established; however, the effects of short-term embryo exposure to arecoline are not understood. Using zebrafish, we study the effects of short-term exposure of arecoline on embryos to model the human habit of areca nut-chewing during early pregnancy. Arecoline, at concentrations from 0.001% to 0.04%, was administered to zebrafish embryos from 4 to 24 hours post fertilization. The morphological changes, survival rates, body length, and skeletal muscle fiber structure were then investigated by immunohistochemistry, confocal microscopy, and conventional electron microscopy. With exposure of embryos to increasing arecoline concentrations, we observed a significant decline in the hatching and survival rates, general growth retardation, lower locomotor activity, and swimming ability impairment. Immunofluorescent staining demonstrated a loose arrangement of myosin heavy chains, and ultrastructural observations revealed altered myofibril arrangement and swelling of the mitochondria. In addition, the results of flow-cytometry and JC-1 staining to assay mitochondria activity, as well as reverse transcription-polymerase chain reaction analyses of functional gene expression, revealed mitochondrial dysfunctions after exposure to arecoline. We confirmed that short-term arecoline exposure resulted in retarded embryonic development and decreased locomotor activity due to defective somitic skeletal muscle development and mitochondrial dysfunction.

  12. Neonatal Repeated Exposure to Isoflurane not Sevoflurane in Mice Reversibly Impaired Spatial Cognition at Juvenile-Age.

    Science.gov (United States)

    Liu, Jianhui; Zhao, Yanhong; Yang, Junjun; Zhang, Xiaoqing; Zhang, Wei; Wang, Peijun

    2017-02-01

    Inhalation anesthetics facilitate surgical procedures in millions of children each year. However, animal studies demonstrate that exposure to the inhalation anesthetic isoflurane may cause neuronal cell death in developing brains. The long-term cytotoxic effects of sevoflurane, the most popular pediatric anesthetic, have not been compared with isoflurane. Thus, this study was designed to compare the effects of equipotent doses of these two anesthetics on neonatal long-term neurotoxicity. Postnatal 7-day-old (P7) C57/BL male mice were exposed to 1.5% isoflurane or 2.2% sevoflurane 2 h a day for 3 days. Non-anesthetized mice served as controls. The effects of anesthesia on learning and memory were assessed using the Morris Water Maze (MWM) at Postnatal days 30 (P30) and P60 respectively. The hippocampal content of N-methyl-D-aspartate receptor subunits (NMDA), brain-derived neurotrophic factor (BDNF), and synaptophysin (Syn) were determined by Western Blot. Neuron structure and apoptosis were assessed via Nissl and TUNEL staining, respectively. The isoflurane group exhibited cognitive impairment at P30. Repeated inhalation of isoflurane or sevoflurane caused different degrees of apoptosis and damaged hippocampal neurons in neonatal mice, particularly isoflurane. In neonatal mice, repeated exposure to isoflurane, but not sevoflurane, caused spatial cognitive impairments in juvenile mice. Our findings suggest that isoflurane induces significantly greater neurodegeneration than an equipotent minimum alveolar concentration of sevoflurane.

  13. 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.

    2014-01-01

    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

  14. Low-normal free thyroxine confers decreased serum bilirubin in type 2 diabetes mellitus

    NARCIS (Netherlands)

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

    2013-01-01

    Background: Bilirubin may confer cardiovascular protection because of its strong antioxidative properties. Both thyroid dysfunction and the diabetic state affect bilirubin metabolism. Here we tested whether low-normal thyroid function affects serum bilirubin among euthyroid subjects with and without

  15. 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....

  16. 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....

  17. 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 hemoc

  18. Aflatoxin exposure during the first 36 months of life was not associated with impaired growth in Nepalese children: An extension of the MAL-ED study

    Science.gov (United States)

    Hsu, Hui-Husan; Chandyo, Ram Krishna; Shrestha, Binob; Bodhidatta, Ladaporn; Tu, Yu-Kang; Gong, Yun-Yun; Egner, Patricia A.; Ulak, Manjeswori; Groopman, John D.; Wu, Felicia

    2017-01-01

    Exposure to aflatoxin, a mycotoxin common in many foods, has been associated with child growth impairment in sub-Saharan Africa. To improve our understanding of growth impairment in relation to aflatoxin and other risk factors, we assessed biospecimens collected in Nepalese children at 15, 24, and 36 months of age for aflatoxin exposure. Children (N = 85) enrolled in the Bhaktapur, Nepal MAL-ED study encompassed the cohort analysed in this study. Exposure was assessed through a plasma biomarker of aflatoxin exposure: the AFB1-lysine adduct. The aflatoxin exposures in the study participants were compared to anthropometrics at each time period (length-for-age [LAZ], weight-for-age [WAZ], and weight-for-length [WLZ] z-scores), growth trajectories over time, age, and breastfeeding status. Results demonstrated chronic aflatoxin exposure in this cohort of children, with a geometric mean of 3.62 pg AFB1-lysine/mg albumin. However, the chronic aflatoxin exposure in this cohort was not significantly associated with anthropometric z-scores, growth trajectories, age, or feeding status, based on the available time points to assess aflatoxin exposure. Low mean levels of aflatoxin exposure and infrequent occurrence of stunting, wasting, or underweight z-score values in this cohort are possible contributing factors to a lack of evidence for an association. Further research is needed to examine whether a threshold dose of aflatoxin exists that could induce child growth impairment. PMID:28212415

  19. Perinatal exposure to low-dose methoxychlor impairs testicular development in C57BL/6 mice.

    Science.gov (United States)

    Du, Xiaohong; Zhang, Hua; Liu, Yuanwu; Yu, Wanpeng; Huang, Chaobin; Li, Xiangdong

    2014-01-01

    Methoxychlor (MXC), an organochlorine pesticide, has adverse effects on male reproduction at toxicological doses. Humans and wild animals are exposed to MXC mostly through contaminated dietary intake. Higher concentrations of MXC have been found in human milk, raising the demand for the risk assessment of offspring after maternal exposure to low doses of MXC. In this study, pregnant mice (F0) were given intraperitoneal daily evening injections of 1 mg/kg/d MXC during their gestational (embryonic day 0.5, E0.5) and lactational periods (postnatal day 21.5, P21.5), and the F1 males were assessed. F1 testes were collected at P0.5, P21.5 and P45.5. Maternal exposure to MXC disturbed the testicular development. Serum testosterone levels decreased, whereas estradiol levels increased. To understand the molecular mechanisms of exposure to MXC in male reproduction, the F1 testes were examined for changes in the expression of steroidogenesis- and spermatogenesis- related genes. RT-PCR analysis demonstrated that MXC significantly decreased Cyp11a1 and increased Cyp19a1; furthermore, it downregulated certain spermatogenic genes (Dazl, Boll, Rarg, Stra8 and Cyclin-a1). In summary, perinatal exposure to low-dose MXC disturbs the testicular development in mice. This animal study of exposure to low-dose MXC in F1 males suggests similar dysfunctional effects on male reproduction in humans.

  20. Intrauterine Exposure to Paracetamol and Aniline Impairs Female Reproductive Development by Reducing Follicle Reserves and Fertility.

    Science.gov (United States)

    Holm, Jacob Bak; Mazaud-Guittot, Severine; Danneskiold-Samsøe, Niels Banhos; Chalmey, Clementine; Jensen, Benjamin; Nørregård, Mette Marie; Hansen, Cecilie Hurup; Styrishave, Bjarne; Svingen, Terje; Vinggaard, Anne Marie; Koch, Holger Martin; Bowles, Josephine; Koopman, Peter; Jégou, Bernard; Kristiansen, Karsten; Kristensen, David Møbjerg

    2016-03-01

    Studies report that fetal exposure to paracetamol/acetaminophen by maternal consumption can interfere with male reproductive development. Moreover, recent biomonitoring data report widespread presence of paracetamol in German and Danish populations, suggesting exposure via secondary (nonpharmaceutical) sources, such as metabolic conversion from the ubiquitous industrial compound aniline. In this study, we investigated the extent to which paracetamol and aniline can interfere with female reproductive development. Intrauterine exposure to paracetamol by gavage of pregnant dams resulted in shortening of the anogenital distance in adult offspring, suggesting that fetal hormone signaling had been disturbed. Female offspring of paracetamol-exposed mothers had ovaries with diminished follicle reserve and reduced fertility. Fetal gonads of exposed animals had also reduced gonocyte numbers, suggesting that the reduced follicle count in adults could be due to early disruption of germ cell development. However, ex vivo cultures of ovaries from 12.5 days post coitum fetuses showed no decrease in proliferation or expression following exposure to paracetamol. This suggests that the effect of paracetamol occurs prior to this developmental stage. Accordingly, using embryonic stem cells as a proxy for primordial germ cells we show that paracetamol is an inhibitor of cellular proliferation, but without cytotoxic effects. Collectively, our data show that intrauterine exposure to paracetamol at levels commonly observed in pregnant women, as well as its precursor aniline, may block primordial germ cell proliferation, ultimately leading to reduced follicle reserves and compromised reproductive capacity later in life.

  1. Perinatal exposure to low-dose methoxychlor impairs testicular development in C57BL/6 mice.

    Directory of Open Access Journals (Sweden)

    Xiaohong Du

    Full Text Available Methoxychlor (MXC, an organochlorine pesticide, has adverse effects on male reproduction at toxicological doses. Humans and wild animals are exposed to MXC mostly through contaminated dietary intake. Higher concentrations of MXC have been found in human milk, raising the demand for the risk assessment of offspring after maternal exposure to low doses of MXC. In this study, pregnant mice (F0 were given intraperitoneal daily evening injections of 1 mg/kg/d MXC during their gestational (embryonic day 0.5, E0.5 and lactational periods (postnatal day 21.5, P21.5, and the F1 males were assessed. F1 testes were collected at P0.5, P21.5 and P45.5. Maternal exposure to MXC disturbed the testicular development. Serum testosterone levels decreased, whereas estradiol levels increased. To understand the molecular mechanisms of exposure to MXC in male reproduction, the F1 testes were examined for changes in the expression of steroidogenesis- and spermatogenesis- related genes. RT-PCR analysis demonstrated that MXC significantly decreased Cyp11a1 and increased Cyp19a1; furthermore, it downregulated certain spermatogenic genes (Dazl, Boll, Rarg, Stra8 and Cyclin-a1. In summary, perinatal exposure to low-dose MXC disturbs the testicular development in mice. This animal study of exposure to low-dose MXC in F1 males suggests similar dysfunctional effects on male reproduction in humans.

  2. Conjugated bilirubin in neonates with glucose-6-phosphate dehydrogenase deficiency.

    Science.gov (United States)

    Kaplan, M; Rubaltelli, F F; Hammerman, C; Vilei, M T; Leiter, C; Abramov, A; Muraca, M

    1996-05-01

    We used a system capable of measuring conjugated bilirubin and its monoconjugated and diconjugated fractions in serum to assess bilirubin conjugation in 29 glucose-6-phosphate dehydrogenase (G6PD)-deficient, term, male newborn infants and 35 control subjects; all had serum bilirubin levels > or = 256 mumol/L (15 mg/dI). The median value for diconjugated bilirubin was lower in the G6PD-deficient neonates than in control subjects (0.06 (range 0.00 to 1.84) vs 0.21 (range 0.00 to 1.02) mumol/L, p = 0.006). Diglucuronide was undetectable in 11 (38.9%) of the G6PD-deficient infants versus 3 (8.6%) of the control subjects (p = 0.015). These findings imply a partial defect of bilirubin conjugation not previously demonstrated in G6PD-deficient newborn infants.

  3. Prenatal Low Dosage Dioxin (TCDD) Exposure Impairs Cochlear Function Resulting in Auditory Neuropathy

    Science.gov (United States)

    Safe, Theresa M.; Luebke, Anne E.

    2015-01-01

    2,3,7,8-tetrachorodibenzo-p-dioxin (TCDD), a ubiquitous and persistent environmental contaminant, is a potent teratogen. Whereas developmental TCDD toxicity is mediated by the aryl hydrocarbon receptor (AhR), the normal function of the AhR is poorly understood. We tested whether dioxin exposure during a critical period of hair cell development disrupts cochlear function in three mouse strains, (C57BL6, BalbC, and CBA) that contain high affinity AhR-b alleles. C57BL/6, BalbC, and CBA dams were exposed to 500 ng/kg TCDD or olive oil (vehicle) on embryonic day 12 by gavage. Cochlear function was analyzed at 1.5 months of age by measuring 1) auditory brainstem response (ABRs) to tone pips from 5.6 to 30 kHz, and 2) distortion-product otoacoustic emissions (DPOAEs) evoked by primaries with f2 at the same frequency values. Cochlear threshold sensitivity following TCDD exposure was significantly elevated in both female and male mice in the C57BL/6 strain, carrying the Ahb-1 allele, but not significantly elevated in the BalbC or CBA strains, carrying the Ahb-2 allele. These ABR threshold deficits in mice carrying the Ahb-1 allele parallels the cleft palate incidence to higher TCDD exposures, suggesting that ABR testing could serve as a sensitive indicator of TCDD toxicity in at-risk children. Moreover, DPOAEs were not affected following TCDD exposure in any of the mouse strains, suggesting that following TCDD exposure mice with the Ahb-1 allele exhibit a mild auditory neuropathy. The causes of many auditory neuropathies are unknown, yet a developmental exposure to dioxin may be a risk factor for this condition. PMID:26464051

  4. Prenatal low dosage dioxin (TCDD) exposure impairs cochlear function resulting in auditory neuropathy.

    Science.gov (United States)

    Safe, Theresa M; Luebke, Anne E

    2016-01-01

    2,3,7,8-tetrachorodibenzo-p-dioxin (TCDD), a ubiquitous and persistent environmental contaminant, is a potent teratogen. Whereas developmental TCDD toxicity is mediated by the aryl hydrocarbon receptor (AhR), the normal function of the AhR is poorly understood. We tested whether dioxin exposure during a critical period of hair cell development disrupts cochlear function in three mouse strains, (C57BL6, BalbC, and CBA) that contain high affinity AhR-b alleles. C57BL/6, BalbC, and CBA dams were exposed to 500 ng/kg TCDD or olive oil (vehicle) on embryonic day 12 by gavage. Cochlear function was analyzed at 1.5 months of age by measuring 1) auditory brainstem response (ABRs) to tone pips from 5.6 to 30 kHz, and 2) distortion-product otoacoustic emissions (DPOAEs) evoked by primaries with f2 at the same frequency values. Cochlear threshold sensitivity following TCDD exposure was significantly elevated in both female and male mice in the C57BL/6 strain, carrying the Ahb-1 allele, but not significantly elevated in the BalbC or CBA strains, carrying the Ahb-2 allele. These ABR threshold deficits in mice carrying the Ahb-1 allele parallels the cleft palate incidence to higher TCDD exposures, suggesting that ABR testing could serve as a sensitive indicator of TCDD toxicity in at-risk children. Moreover, DPOAEs were not affected following TCDD exposure in any of the mouse strains, suggesting that following TCDD exposure mice with the Ahb-1 allele exhibit a mild auditory neuropathy. The causes of many auditory neuropathies are unknown, yet a developmental exposure to dioxin may be a risk factor for this condition.

  5. 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.

  6. Cognitive and Behavioral Impairments Evoked by Low-Level Exposure to Tobacco Smoke Components: Comparison with Nicotine Alone.

    Science.gov (United States)

    Hall, Brandon J; Cauley, Marty; Burke, Dennis A; Kiany, Abtin; Slotkin, Theodore A; Levin, Edward D

    2016-06-01

    Active maternal smoking has adverse effects on neurobehavioral development of the offspring, with nicotine (Nic) providing much of the underlying causative mechanism. To determine whether the lower exposures caused by second-hand smoke are deleterious, we administered tobacco smoke extract (TSE) to pregnant rats starting preconception and continued through the second postnatal week, corresponding to all 3 trimesters of fetal brain development. Dosing was adjusted to produce maternal plasma Nic concentrations encountered with second-hand smoke, an order of magnitude below those seen in active smokers. We then compared TSE effects to those of an equivalent dose of Nic alone, and to a 10-fold higher Nic dose. Gestational exposure to TSE and Nic significantly disrupted cognitive and behavioral function in behavioral tests given during adolescence and adulthood (postnatal weeks 4-40), producing hyperactivity, working memory deficits, and impairments in emotional processing, even at the low exposure levels corresponding to second-hand smoke. Although TSE effects were highly correlated with those of Nic, the effects of TSE were much larger than could be attributed to just the Nic in the mixture. Indeed, TSE effects more closely resembled those of the 10-fold higher Nic levels, but still exceeded their magnitude. In combination with our earlier findings, this study thus completes the chain of causation to prove that second-hand smoke exposure causes neurodevelopmental deficits, originating in disruption of neurodifferentiation, leading to miswiring of neuronal circuits, and as shown here, culminating in behavioral dysfunction. As low level exposure to Nic alone produced neurobehavioral teratology, 'harm reduction' Nic products do not abolish the potential for neurodevelopmental damage.

  7. Fetal Exposure to Sertraline Hydrochloride Impairs Pancreatic β-Cell Development.

    Science.gov (United States)

    De Long, Nicole E; Gutgesell, Marie K; Petrik, James J; Holloway, Alison C

    2015-06-01

    Ten percent to 15% of women take selective serotonin reuptake inhibitor (SSRI) antidepressants during pregnancy. Offspring exposed to SSRIs are more likely to have low birth weight; this is associated with an increased risk of development of diabetes in adulthood in part due to altered pancreatic development. The effects of perinatal exposure to SSRIs on pancreatic development are unknown. Therefore, the objective of this study was to determine the effect of fetal exposure to sertraline hydrochloride on pregnancy outcomes and pancreatic development. Wistar rats were given vehicle (n = 5) or sertraline hydrochloride (10 mg/kg/d; n = 8) via daily subcutaneous injection from the confirmation of mating until parturition. Results from this animal model demonstrated that offspring born to sertraline-exposed dams have no changes in birth weight but had a reduction in pancreatic β-cell area. The altered pancreatic islet development was a result of altered gene expression regulating islet development and survival. Therefore, fetal exposure to sertraline reduces β-cell capacity at birth, raising concerns regarding the long-term metabolic sequelae of such exposures.

  8. Sleep alterations following exposure to stress predict fear-associated memory impairments in a rodent model of PTSD.

    Science.gov (United States)

    Vanderheyden, William M; George, Sophie A; Urpa, Lea; Kehoe, Michaela; Liberzon, Israel; Poe, Gina R

    2015-08-01

    Sleep abnormalities, such as insomnia, nightmares, hyper-arousal, and difficulty initiating or maintaining sleep, are diagnostic criteria of posttraumatic stress disorder (PTSD). The vivid dream state, rapid eye movement (REM) sleep, has been implicated in processing emotional memories. We have hypothesized that REM sleep is maladaptive in those suffering from PTSD. However, the precise neurobiological mechanisms regulating sleep disturbances following trauma exposure are poorly understood. Using single prolonged stress (SPS), a well-validated rodent model of PTSD, we measured sleep alterations in response to stressor exposure and over a subsequent 7-day isolation period during which the PTSD-like phenotype develops. SPS resulted in acute increases in REM sleep and transition to REM sleep, and decreased waking in addition to alterations in sleep architecture. The severity of the PTSD-like phenotype was later assessed by measuring freezing levels on a fear-associated memory test. Interestingly, the change in REM sleep following SPS was significantly correlated with freezing behavior during extinction recall assessed more than a week later. Reductions in theta (4-10 Hz) and sigma (10-15 Hz) band power during transition to REM sleep also correlated with impaired fear-associated memory processing. These data reveal that changes in REM sleep, transition to REM sleep, waking, and theta and sigma power may serve as sleep biomarkers to identify individuals with increased susceptibility to PTSD following trauma exposure.

  9. Intrauterine Exposure to Paracetamol and Aniline Impairs Female Reproductive Development by Reducing Follicle Reserves and Fertility

    DEFF Research Database (Denmark)

    Holm, Jacob Bak; Mazaud-Guittot, Severine; Danneskiold-Samsøe, Niels Banhos

    2016-01-01

    of paracetamol occurs prior to this developmental stage. Accordingly, using embryonic stem cells as a proxy for primordial germ cells we show that paracetamol is an inhibitor of cellular proliferation, but without cytotoxic effects. Collectively, our data show that intrauterine exposure to paracetamol at levels...... in shortening of the anogenital distance in adult offspring, suggesting that fetal hormone signaling had been disturbed. Female offspring of paracetamol-exposed mothers had ovaries with diminished follicle reserve and reduced fertility. Fetal gonads of exposed animals had also reduced gonocyte numbers......, suggesting that the reduced follicle count in adults could be due to early disruption of germ cell development. However, ex vivo cultures of ovaries from 12.5 days post coitum fetuses showed no decrease in proliferation or expression following exposure to paracetamol. This suggests that the effect...

  10. Prenatal exposure to di(2-ethylhexyl) phthalate impairs development of the mouse neocortex.

    Science.gov (United States)

    Komada, Munekazu; Gendai, Yuuya; Kagawa, Nao; Nagao, Tetsuji

    2016-09-30

    Di(2-ethylhexyl) phthalate (DEHP) is currently the most commonly used phthalate for the production of flexible polyvinyl chloride. Phthalates including DEHP have been labeled as potential endocrine disruptors. The effect on the development of the neocortex, however, is unknown. To evaluate the neurodevelopmental effects of prenatal DEHP exposure at 1 and 100mg/kg/day or 100 and 500mg/kg/day in fetal and newborn mice, we performed a detailed histologic analysis of the developing dorsal telencephalon and neocortex. The observation of fetuses exposed to DEHP revealed reductions of proliferation and neurogenesis (1 and 100mg/kg) and an increase in cell death (500mg/kg). In addition, the newborns prenatally exposed to DEHP showed an abnormal neuronal distribution and a decrease in neurons. These findings suggest that prenatal DEHP exposure induces neurodevelopmental toxicity associated with the neural stem cell niche and corticogenesis.

  11. Di (2-ethylhexyl Phthalate Exposure Impairs Growth of Antral Follicle in Mice.

    Directory of Open Access Journals (Sweden)

    Lan Li

    Full Text Available Di (2-ethylhexyl phthalate (DEHP is a widely used plastic additive. As an environmental endocrine disruptor, it has been shown to be harmful to the mammalian reproductive system. Previous studies indicated that DEHP inhibited the development of mouse ovarian follicles. However, the mechanisms by which DEHP affects ovarian antral follicle development during the pre-puberty stage are poorly understand. Thus, we investigated the effects of direct DEHP exposure on antral follicle growth in pre-pubescent mice by use of intraperitoneal injection. Our results demonstrated that the percentage of large antral follicles was significantly reduced when mice were exposed to 20 or 40 μg/kg DEHP every 5 days from postnatal day 0 (0 dpp to 15 dpp. In 20 dpp, we performed microarray of these ovaries. The microarray results indicated that mRNA levels of apoptosis related genes were increased. The mRNA levels of the apoptosis and cell proliferation (negative related genes Apoe, Agt, Glo1 and Grina were increased after DEHP exposure. DEHP induced the differential gene expression of Hsp90ab1, Rhoa, Grina and Xdh which may play an important role in this process. In addition, TUNEL staining and immunofluorescence showed that DEHP exposure significantly increased the number of TUNEL, Caspase3 and γH2AX positive ovarian somatic cells within the mouse ovaries. Flow cytometer analyses of redox-sensitive probes showed that DEHP caused the accumulation of reactive oxygen species. Moreover, the mRNA expression of ovarian somatic cell antioxidative enzymes was down-regulated both in vivo and in vitro. In conclusion, our data here demonstrated that DEHP exposure induced oxidative stress and ovarian somatic cell apoptosis, and thus may impact antral follicle enlargement during the pre-pubertal stage in mice.

  12. Association of perfluoroalkyl substances exposure with impaired lung function in children.

    Science.gov (United States)

    Qin, Xiao-Di; Qian, Zhengmin Min; Dharmage, Shyamali C; Perret, Jennifer; Geiger, Sarah Dee; Rigdon, Steven E; Howard, Steven; Zeng, Xiao-Wen; Hu, Li-Wen; Yang, Bo-Yi; Zhou, Yang; Li, Meng; Xu, Shu-Li; Bao, Wen-Wen; Zhang, Ya-Zhi; Yuan, Ping; Wang, Jia; Zhang, Chuan; Tian, Yan-Peng; Nian, Min; Xiao, Xiang; Chen, Wen; Lee, Yungling Leo; Dong, Guang-Hui

    2017-02-04

    Previous studies have demonstrated associations between serum levels of perfluoroalkyl substances (PFASs) and asthma or asthma related-biomarkers. However, no studies have reported a possible relationship between PFASs exposure and lung function among children. The objective of the present study is to test the association between PFASs exposure and lung function in children from a high exposure area by using a cross-sectional case-control study, which included 132 asthmatic children and 168 non-asthmatic controls recruited from 2009 to 2010 in the Genetic and Biomarkers study for Childhood Asthma. Structured questionnaires were administered face-to-face. Lung function was measured by spirometry. Linear regression models were used to examine the influence of PFASs on lung function. The results showed that asthmatics in our study had significantly higher serum PFAS concentrations than healthy controls. Logistic regression models showed a positive association between PFASs and asthma, with adjusted odds ratios (ORs) ranging from 0.99 (95% confidence interval [CI]: 0.80-1.21) to 2.76 (95% CI: 1.82-4.17). Linear regression modeling showed serum PFASs levels were significantly negatively associated with three pulmonary function measurements (forced vital capacity: FVC; forced expiratory volume in 1s: FEV1; forced expiratory flow 25-75%: FEF25-75) among children with asthma, the adjusted coefficients between lung function and PFASs exposure ranged from -0.055 (95%CI: -0.100 to -0.010) for FVC and perfluorooctane sulfonate (PFOS) to -0.223 (95%CI: -0.400 to -0.045) for FEF25-75 and perfluorooctanoic acid (PFOA). PFASs were not, however, significantly associated with pulmonary function among children without asthma. In conclusion, this study suggests that serum PFASs are associated with decreased lung function among children with asthma.

  13. Maternal cypermethrin exposure during the perinatal period impairs testicular development in C57BL male offspring.

    Directory of Open Access Journals (Sweden)

    Chaobin Huang

    Full Text Available Numerous studies have demonstrated that endocrine-disrupting compounds (EDC are a possible cause of male reproductive organ malfunction and malformation. Cypermethrin (CYP is a widely used synthetic pyrethroid and a potential EDC. This study aimed to examine the effects of perinatal exposure to low-dose CYP on the development and function of the offspring testes. Pregnant mice were intragastrically administered 0.12 to 12 mg/kg/day CYP from embryonic day 0.5 (E0.5 to weaning (PD21.5, postnatal day 21.5. Maternal exposure to 0.12, 1.2, and 12 mg/kg/day CYP affected the body and organ weight of the offspring. Exposure of CYP led to a dose-dependent decrease in the male-to-female sex ratio. A histopathological analysis revealed a thinner seminiferous epithelium layer at PD21.5, interstitial hyperplasia at PD45.5, and germ cell vacuolization at PD90.5 in the 12 mg/kg/day CYP group. The TUNEL assay results revealed increased germ cell apoptosis in the 12 mg/kg/day CYP group. The serum testosterone (T level decreased, whereas the estradiol level increased with age in the 1.2 and 12 mg/kg/day CYP groups. The RT-PCR analysis demonstrated decreased expression of T production-related, mitosis-related, and meiosis-related genes in the 1.2 and 12 mg/kg/day CYP groups. The in vitro experimental results demonstrated reduced expression of steroidogenesis genes and decreased T levels. It is concluded that perinatal exposure to low-dose CYP affects testes development and function in adults.

  14. Relationship between serum bilirubin levels and optic neuritis

    Institute of Scientific and Technical Information of China (English)

    DENG Juan; LIANG Xue-mei; ZHANG Xiu-lan; LING Shi-qi; YANG Ting-ting; LI Min; PENG Fu-hua

    2013-01-01

    Background Bilirubin is the end product of heme catabolism and has strong antioxidant properties.Serum bilirubin levels are reported to be reduced in patients with multiple sclerosis (MS) and neuromyelitis optica (NMO).The pathophysiology of optic neuritis (ON) resembles that of MS; however,the role of endogenous bilirubin in ON is unclear.The aim of this study is to measure serum bilirubin levels in patients with ON,and to investigate the correlation between ON and serum antioxidant status of bilirubin.Methods Serum levels of bilirubin were measured in 42 patients with ON,50 patients with multiple sclerosis (MS),48 patients with neuromyelitis optica (NMO) and 48 healthy control subjects.Results Serum total bilirubin (Tbil),direct bilirubin (Dbil) and indirect bilirubin (Ibil) levels in patients with ON were significantly lower than those in the healthy controls.However,no statistical significance was found between levels in the ON and MS,ON and NMO,and MS and NMO groups.In patients with ON,serum Tbil,Dbil,and Ibil levels were lower in those with recurrence or those with ON for a longer duration (>1 year).Moreover,Tbil,Dbil,and Ibil concentrations were lower in patients with papillitis than in those with retrobulbar type ON,but the differences were not statistically significant.Conclusions Low antioxidant status may exist in patients with ON.But serum levels of Tbil,Dbil,and Ibil did not correlate with clinical presentations,such as recurrence,duration of disease and subtypes of ON.Low antioxidant status already existed in MS or NMO patients before systemic symptoms appeared.

  15. Cocaine exposure impairs multilineage hematopoiesis of human hematopoietic progenitor cells mediated by the sigma-1 receptor [corrected].

    Science.gov (United States)

    Nixon, Christopher C; Schwartz, Brandon H; Dixit, Dhaval; Zack, Jerome A; Vatakis, Dimitrios N

    2015-03-02

    Prenatal exposure to cocaine is a significant source of fetal and neonatal developmental defects. While cocaine associated neurological and cardiac pathologies are well-documented, it is apparent that cocaine use has far more diverse physiological effects. It is known that in some cell types, the sigma-1 receptor mediates many of cocaine's cellular effects. Here we present a novel and concise investigation into the mechanism that underlies cocaine associated hematopoietic pathology. Indeed, this is the first examination of the effects of cocaine on hematopoiesis. We show that cocaine impairs multilineage hematopoiesis from human progenitors from multiple donors and tissue types. We go on to present the first demonstration of the expression of the sigma-1 receptor in human CD34 + human hematopoietic stem/progenitor cells. Furthermore, we demonstrate that these cocaine-induced hematopoietic defects can be reversed through sigma-1 receptor blockade.

  16. Prenatal exposure to fenugreek impairs sensorimotor development and the operation of spinal cord networks in mice.

    Directory of Open Access Journals (Sweden)

    Loubna Khalki

    Full Text Available Fenugreek is a medicinal plant whose seeds are widely used in traditional medicine, mainly for its laxative, galactagogue and antidiabetic effects. However, consumption of fenugreek seeds during pregnancy has been associated with a range of congenital malformations, including hydrocephalus, anencephaly and spina bifida in humans. The present study was conducted to evaluate the effects of prenatal treatment of fenugreek seeds on the development of sensorimotor functions from birth to young adults. Pregnant mice were treated by gavage with 1 g/kg/day of lyophilized fenugreek seeds aqueous extract (FSAE or distilled water during the gestational period. Behavioral tests revealed in prenatally treated mice a significant delay in righting, cliff avoidance, negative geotaxis responses and the swimming development. In addition, extracellular recording of motor output in spinal cord isolated from neonatal mice showed that the frequency of spontaneous activity and fictive locomotion was reduced in FSAE-exposed mice. On the other hand, the cross-correlation coefficient in control mice was significantly more negative than in treated animals indicating that alternating patterns are deteriorated in FSAE-treated animals. At advanced age, prenatally treated mice displayed altered locomotor coordination in the rotarod test and also changes in static and dynamic parameters assessed by the CatWalk automated gait analysis system. We conclude that FSAE impairs sensorimotor and coordination functions not only in neonates but also in adult mice. Moreover, spinal neuronal networks are less excitable in prenatally FSAE-exposed mice suggesting that modifications within the central nervous system are responsible, at least in part, for the motor impairments.

  17. Residential exposure to chlorinated hydrocarbons from groundwater contamination and the impairment of renal function-An ecological study

    Science.gov (United States)

    Chen, Hui-Ming; Wu, Ming-Tsang

    2017-01-01

    Groundwater pollution from the petrochemical industry causes serious deterioration of soil and groundwater quality and impacts on human health worldwide. However, few studies have examined the effect of residential exposure to petrochemical chlorinated hydrocarbon-contaminated groundwater on renal function impairment in humans. We conducted an ecological study to investigate the two. A polyvinyl chloride (PVC) plant was located in one of the six villages, the study area, in Kaohsiung city of southwestern Taiwan. Based on the direction of groundwater flow and previous groundwater measurements of chlorinated hydrocarbons from Taiwan Environmental Protection Bureau, we divided the six villages into highly-polluted villages, moderately-polluted villages, and a non-polluted village. All inhabitants in those six villages were invited to receive free health examinations between May-June, 2010. In total, 4,432 study subjects ≥18 yrs old were analyzed. Compared to those in the non-polluted village, subjects in highly-polluted villages had 1.89- and 1.46-fold the risk of impaired estimated glomerular filtration rate (eGFR) and proteinuria (95% CI = 1.15–1.85 and 1.09–3.28, respectively) after adjusting for other covariates. Given this relative large sample size, we found that groundwater chlorinated hydrocarbon pollution can cause kidney damage in adults. PMID:28067285

  18. Impaired spatial learning and unaltered neurogenesis in a transgenic model of Alzheimer's disease after oral aluminum exposure.

    Science.gov (United States)

    Ribes, D; Colomina, M T; Vicens, P; Domingo, J L

    2010-08-01

    Although it is well established that aluminum (Al) is neurotoxic, the potential role of this element in the etiology of Alzheimer's disease (AD) is not well established. In this study, we evaluated the effects of oral Al exposure on spatial learning, memory and neurogenesis in Tg2576 mice, an animal model of AD in which Abeta plaques start to be deposited at 9 months of age. Aluminum was given as Al lactate (11 mg/g of food) for 6 months. At 11 months of age a water maze test was carried out to evaluate learning and memory. Subsequently, mice were injected with bromo-deoxyuridine (BrdU) and sacrificed 24 hours or 28 days after the last injection in order to assess proliferation, survival and differentiation of neurons. We observed impaired acquisition in the water maze task in Al-treated Tg2576 mice, as well as worse memory in the Al-exposed groups. In terms of neurogenesis, no effects of aluminum were observed in proliferation, survival and differentiation. The results of this investigation suggest that Tg2576 mice fed for 210 days with rodent chow supplemented with Al lactate at 11 mg/g of food have impaired spatial learning although their neurogenesis remains unmodified.

  19. Residential exposure to chlorinated hydrocarbons from groundwater contamination and the impairment of renal function-An ecological study

    Science.gov (United States)

    Chen, Hui-Ming; Wu, Ming-Tsang

    2017-01-01

    Groundwater pollution from the petrochemical industry causes serious deterioration of soil and groundwater quality and impacts on human health worldwide. However, few studies have examined the effect of residential exposure to petrochemical chlorinated hydrocarbon-contaminated groundwater on renal function impairment in humans. We conducted an ecological study to investigate the two. A polyvinyl chloride (PVC) plant was located in one of the six villages, the study area, in Kaohsiung city of southwestern Taiwan. Based on the direction of groundwater flow and previous groundwater measurements of chlorinated hydrocarbons from Taiwan Environmental Protection Bureau, we divided the six villages into highly-polluted villages, moderately-polluted villages, and a non-polluted village. All inhabitants in those six villages were invited to receive free health examinations between May-June, 2010. In total, 4,432 study subjects ≥18 yrs old were analyzed. Compared to those in the non-polluted village, subjects in highly-polluted villages had 1.89- and 1.46-fold the risk of impaired estimated glomerular filtration rate (eGFR) and proteinuria (95% CI = 1.15–1.85 and 1.09–3.28, respectively) after adjusting for other covariates. Given this relative large sample size, we found that groundwater chlorinated hydrocarbon pollution can cause kidney damage in adults.

  20. 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...

  1. Endosulfan exposure inhibits brain AChE activity and impairs swimming performance in adult zebrafish (Danio rerio).

    Science.gov (United States)

    Pereira, Vanessa Maynart; Bortolotto, Josiane Woutheres; Kist, Luiza Wilges; Azevedo, Mariana Barbieri de; Fritsch, Rachel Seemann; Oliveira, Renata da Luz; Pereira, Talita Carneiro Brandão; Bonan, Carla Denise; Vianna, Monica Ryff; Bogo, Maurício Reis

    2012-06-01

    Endosulfan is a broad spectrum organochlorine pesticide that is still widely in use in many developing countries. Following application, endosulfan can get to watercourses through surface runoff from agricultural fields and disturb the non-target aquatic animals including freshwater fish species. Given that the activity of the enzyme acetylcholinesterase (AChE) is one of the most recurrently used biomarkers of exposure to pesticides and there are controversial results concerning the effects of endosulfan exposure and AChE activity in fish, the aim of the present study was to evaluate the effects of endosulfan in brain AChE activity and its gene expression pattern using adult zebrafish (Danio rerio) as an animal model. Moreover, we have analyzed the effects of endosulfan exposure in different parameters of zebrafish swimming activity and in long-term memory formation. After 96 h of exposition, fish in the 2.4 μg endosulfan/L group presented a significant decrease in AChE activity (9.44 ± 1.038 μmol SCh h(-1) mg protein(-1); p=0.0205) when compared to the control group (15.87 ± 1.768 μmol SCh h(-1) mg protein(-1); p=0.0205) which corresponds to approximately 40%. The down-regulation of brain AChE activity is not directly related with the transcriptional control as demonstrated by the RT-qPCR analysis. Our results reinforce AChE activity inhibition as a pathway of endosulfan-induced toxicity in brain of fish species. In addition, exposure to 2.4 μg endosulfan/L during 96 h impaired all exploratory parameters evaluated: decreased line crossings (≈21%, 273.7 ± 28.12 number of line crossings compared to the control group 344.6 ± 21.30, p=0.0483), traveled distance (≈20%, 23.44 ± 2.127 m compared to the control group 29.39 ± 1.585, p=0.0281), mean speed (≈25%, 0.03 ± 0.003 m/s compared to the control group 0.04 ± 0.002, p=0.0275) and body turn angle (≈21%, 69,940 ± 4871 absolute turn angle compared to the control group 88,010 ± 4560, p=0.0114). These

  2. Transcutaneous bilirubin nomograms in African neonates

    Science.gov (United States)

    Mabogunje, Cecilia A.; Imosemi, Donald O.; Emokpae, Abieyuwa A.

    2017-01-01

    Background The use of transcutaneous bilirubin (TcB) as a screening tool, based on relevant population-specific nomogram, or proxy for total serum bilirubin (TSB) levels in assessing the risk of subsequent hyperbilirubinemia is supported by several clinical guidelines on the management of neonatal hyperbilirubinemia. However, while TcB has been found to significantly over-estimate TSB in neonates of African-American ancestry, with variations across TcB devices, no nomogram has been specifically reported for this racial group. This study therefore set out to develop TcB nomograms for healthy late pre-term and term black African neonates derived from two widely used bilirubinometers. Methods A retrospective analysis of 12,377 TcB measurements obtained from 6,373 neonates in the first postnatal week, over a period of 48 months using Bilichek and JM-103 bilirubinometers. TcB percentiles were computed from hour-specific TcB values and nomograms developed for each of the screening devices. Predictive ability of the 75th and 95th percentiles to detect significant hyperbilirubinemia was evaluated between 24–96 hours of age. The 95th percentile curve was compared with those from other populations. Results The velocity of TcB rise at 75th and 95th percentiles was generally higher with JM-103 than Bilichek. Both percentiles also peaked at higher TcB levels with JM-103. The 95th percentile for both instruments showed a downward trend as from approximately 114 hours. Both instruments had high negative predictive values across the selected time-epochs and lower discriminatory ability than reported in non-black populations. Conclusions The predictive utility of TcB as a potential screening tool varies across devices in black African neonates with or without risk of significant hyperbilirubinemia, and lower than levels reported in non-black populations. Equipment-specific nomograms should be considered for TcB monitoring in this racial population where TSB is not routinely

  3. Lead exposure impairs NMDA agonist-induced no production in pyramidal hippocampal cells

    Directory of Open Access Journals (Sweden)

    Seyed Nasser Ostad

    2006-03-01

    Full Text Available Chronic exposure to Lead (Pb affects neural functions in central nervous system (CNS particularly the learning and memory. On the other hand, alteration of calcium level in the CNS results in activation of NOS where it is expected to increase nitric oxide level in hippocampus. In this study the role of Lead exposure in NMDA induced NO production in pyramidal hippocampal cells (CA1HP was investigated. The NO level was determined by measurement of concentration of nitrite and nitrate as NO products using the metHb production at 401 nm. The ACBD (NMDA agonist-induced NO level was almost reduced to the control level (2.5 nM in the presence of 10 and 100 nM of Lead acetate. Lead acetate at concentrations which normally results in chronic toxicity did not increase the nitric oxide (NO production by CA1HP. One reason for this finding could be the interaction of Lead with NMDA receptors due to similarity of Pb2+ to Zn2+ ion. Another reason may be related to direct interaction of Lead with NMDA receptors that inhibit the stimulated NO production.

  4. Single and repeated sevoflurane or desflurane exposure does not impair spatial memory performance of young adult mice.

    Science.gov (United States)

    Kilicaslan, Alper; Belviranli, Muaz; Okudan, Nilsel; Nurullahoglu Atalik, Esra

    2013-12-01

    Volatile anesthetics are known to disturb the spatial memory in aged rodents, but there is insufficient information on their effects on young adult rodents. The aim of this study was to compare the effects of single and repeated exposure to desflurane and sevoflurane on spatial learning and memory functions in young adult mice. Balb/c mice (2 months old) were randomly divided into six equal groups (n = 8). The groups with single inhalation were exposed to 3.3% sevoflurane or 7.8% desflurane or vehicle gas for 4 h, respectively. The groups with repeated inhalation were exposed to 3.3% sevoflurane or 7.8% desflurane or vehicle gas for 2 h a day during 5 consecutive days. Spatial learning and memory were tested in the Morris water maze 24 h after exposure. In the learning phase, the parameters associated with finding the hidden platform and swimming speed, and in the memory phase, time spent in the target quadrant and the adjacent quadrants, were assessed and compared between the groups. In the 4-day learning process, there was no significant difference between the groups in terms of mean latency to platform, mean distance traveled and average speed (P > 0.05). During the memory-test phase, all mice exhibited spatial memory, but there was no significant difference between the groups in terms of time spent in the target quadrant (P > 0.05). Sevoflurane and desflurane anesthesia did not impair acquisition learning and retention memory in young adult mice.

  5. Gallium arsenide exposure impairs processing of particulate antigen by macrophages: modification of the antigen reverses the functional defect.

    Science.gov (United States)

    Hartmann, Constance B; McCoy, Kathleen L

    2004-06-11

    Gallium arsenide (GaAs), a semiconductor used in the electronics industry, causes systemic immunosuppression in animals. The chemical's impact on macrophages to process the particulate antigen, sheep red blood cells (SRBC), for a T cell response in culture was examined after in vivo exposure of mice. GaAs-exposed splenic macrophages were defective in activating SRBC-primed lymph node T cells that could not be attributed to impaired phagocytosis. Modified forms of SRBC were generated to examine the compromised function of GaAs-exposed macrophages. SRBC were fixed to maintain their particulate nature and subsequently delipidated with detergent. Delipidation of intact SRBC was insufficient to restore normal antigen processing in GaAs-exposed macrophages. However, chemically exposed cells efficiently processed soluble sheep proteins. These findings suggest that the problem may lie in the release of sequestered sheep protein antigens, which then could be effectively cleaved to peptides. Furthermore, opsonization of SRBC with IgG compensated for the macrophage processing defect. The influence of signal transduction and phagocytosis via Fcgamma receptors on improved antigen processing could be dissociated. Immobilized anti-Fcgamma receptor antibody activated macrophages to secrete a chemokine, but did not enhance processing of unmodified SRBC by GaAs-exposed macrophages. Restoration of normal processing of particulate SRBC by chemically exposed macrophages involved phagocytosis through Fcgamma receptors. Hence, initial immune responses may be very sensitive to GaAs exposure, and the chemical's immunosuppression may be averted by opsonized particulate antigens.

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

    NARCIS (Netherlands)

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

    2013-01-01

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

  7. Does longstanding nicotine exposure impair bone healing and osseointegration? An experimental study in rabbits

    DEFF Research Database (Denmark)

    Gotfredsen, Klaus; Lindh, Christian H; Berglundh, Tord

    2009-01-01

    OBJECTIVES: The aim of this study was to analyze the effect of longstanding nicotine exposure on bone healing and osseointegration of titanium implants. MATERIALS AND METHODS: 20 female rabbits received either nicotine (n = 10) or saline (n = 10) administered subcutaneously via mini-osmotic pumps...... for 32 weeks. The pump delivered 6 microg/kg/min of nicotine for the animals in the test group. Blood samples were collected and plasma cotinine levels were measured monthly. Six months after the commencement of nicotine or saline administration three osteotomy preparations, one in right, femoral condyle...... and two in the right tibia were made. One experimental implant was placed in the femur site and one in the most distal preparation of the tibia. The remaining site in the tibia was left empty. The osteotomy preparation and implant installation procedure was repeated in the left leg of the rabbits after 2...

  8. Acute paraquat exposure impairs colonic motility by selectively attenuating nitrergic signalling in the mouse.

    Science.gov (United States)

    Diss, Lucy; Dyball, Sarah; Ghela, Tina; Golding, Jonathan; Morris, Rachel; Robinson, Stephen; Tucker, Rosemary; Walter, Talia; Young, Paul; Allen, Marcus; Fidalgo, Sara; Gard, Paul; Mabley, Jon; Patel, Bhavik; Chatterjee, Prabal; Yeoman, Mark

    2016-02-01

    Paraquat, a common herbicide, is responsible for large numbers of deaths worldwide through both deliberate and accidental ingestion. Previous studies have eluded that the bioavailability of paraquat increases substantially with increasing dose and that these changes may in part be due to the effects that these high concentrations have on the gastrointestinal tract (GI tract). To date, the actions of acute, high concentrations (20mM for 60 min) of paraquat on the GI tract, particularly the colon which is a major site of paraquat absorption, are unknown. This study examined the effects of acute paraquat administration on colonic motility in the C57BL/6 mouse. Acute paraquat exposure decreased colonic motility and the amplitude of colonic migrating motor complexes (CMMCs), which are major motor patterns involved in faecal pellet propulsion. In isolated segments of distal colon, paraquat increased resting tension and markedly attenuated electrical field stimulation-evoked relaxations. Pharmacological dissection of paraquat's mechanism of action on both the CMMCs and field stimulated tissue using the nitric oxide synthase inhibitor NG-nitro-L-arginine and direct measurement of NO release from the myenteric plexus, demonstrated that paraquat selectively attenuates nitrergic signalling pathways. These changes did not appear to be due to alterations in colonic oxidative stress, inflammation or complex 1 activity, but were most likely caused by paraquat's ability to act as a redox couple. In summary, these data demonstrate that acute paraquat exposure attenuates colonic transit. These changes may facilitate the absorption of paraquat into the circulation and so facilitate its toxicity.

  9. Could myelin damage from radiofrequency electromagnetic field exposure help explain the functional impairment electrohypersensitivity? A review of the evidence.

    Science.gov (United States)

    Redmayne, Mary; Johansson, Olle

    2014-01-01

    Myelin provides the electrical insulation for the central and peripheral nervous system and develops rapidly in the first years of life, but continues into mid-life or later. Myelin integrity is vital to healthy nervous system development and functioning. This review outlines the development of myelin through life, and then considers the evidence for an association between myelin integrity and exposure to low-intensity radiofrequency electromagnetic fields (RF-EMFs) typical in the modern world. In RF-EMF peer-reviewed literature examining relevant impacts such as myelin sheath, multiple sclerosis, and other myelin-related diseases, cellular examination was included. There are surprisingly little data available in each area, but considered together a picture begins to emerge in RF-EMF-exposed cases: (1) significant morphological lesions in the myelin sheath of rats; (2) a greater risk of multiple sclerosis in a study subgroup; (3) effects in proteins related to myelin production; and (4) physical symptoms in individuals with functional impairment electrohypersensitivity, many of which are the same as if myelin were affected by RF-EMF exposure, giving rise to symptoms of demyelination. In the latter, there are exceptions; headache is common only in electrohypersensitivity, while ataxia is typical of demyelination but infrequently found in the former group. Overall, evidence from in vivo and in vitro and epidemiological studies suggests an association between RF-EMF exposure and either myelin deterioration or a direct impact on neuronal conduction, which may account for many electrohypersensitivity symptoms. The most vulnerable are likely to be those in utero through to at least mid-teen years, as well as ill and elderly individuals.

  10. Exposure to Kynurenic Acid during Adolescence Increases Sign-tracking and Impairs Long-term Potentiation in Adulthood

    Directory of Open Access Journals (Sweden)

    Nicole eDeAngeli

    2015-01-01

    Full Text Available Changes in brain reward systems are thought to contribute significantly to the cognitive and behavioral impairments of schizophrenia, as well as the propensity to develop co-occurring substance abuse disorders. Presently there are few treatments for persons with a dual-diagnosis and little is known about the neural substrates that underlie co-occurring schizophrenia and substance abuse. One goal of the present study was to determine if a change in the concentration of kynurenic acid (KYNA, a tryptophan metabolite that is increased in the brains of people with schizophrenia, affects reward-related behavior. KYNA is an endogenous antagonist of NMDA glutamate receptors and α7 nicotinic acetylcholine receptors, both of which are critically involved in neurodevelopment, plasticity, and behavior. In Experiment 1, rats were treated throughout adolescence with l-kynurenine (L-KYN, the precursor of KYNA. As adults, the rats were tested drug-free in an autoshaping procedure in which a lever was paired with food. Rats treated with L-KYN during adolescence exhibited increased sign-tracking behavior (lever pressing when they were tested as adults. Sign-tracking is thought to reflect the lever acquiring incentive salience (motivational value as a result of its pairing with reward. Thus, KYNA exposure may increase the incentive salience of cues associated with reward, perhaps contributing to an increase in sensitivity to drug-related cues in persons with schizophrenia. In Experiment 2, we tested the effects of exposure to KYNA during adolescence on hippocampal long-term potentiation (LTP. Rats treated with L-KYN exhibited no LTP after a burst of high frequency stimulation that was sufficient to produce robust LTP in vehicle-treated rats. This finding represents the first demonstrated consequence of elevated KYNA concentration during development and provides insight into the basis for cognitive and behavioral deficits that result from exposure to KYNA during

  11. Early-life exposure to climate change impairs tropical shark survival.

    Science.gov (United States)

    Rosa, Rui; Baptista, Miguel; Lopes, Vanessa M; Pegado, Maria Rita; Paula, José Ricardo; Trübenbach, Katja; Leal, Miguel Costa; Calado, Ricardo; Repolho, Tiago

    2014-10-22

    Sharks are one of the most threatened groups of marine animals worldwide, mostly owing to overfishing and habitat degradation/loss. Although these cartilaginous fish have evolved to fill many ecological niches across a wide range of habitats, they have limited capability to rapidly adapt to human-induced changes in their environments. Contrary to global warming, ocean acidification was not considered as a direct climate-related threat to sharks. Here we show, for the first time, that an early ontogenetic acclimation process of a tropical shark (Chiloscyllium punctatum) to the projected scenarios of ocean acidification (ΔpH = 0.5) and warming (+4°C; 30°C) for 2100 elicited significant impairments on juvenile shark condition and survival. The mortality of shark embryos at the present-day thermal scenarios was 0% both at normocapnic and hypercapnic conditions. Yet routine metabolic rates (RMRs) were significantly affected by temperature, pH and embryonic stage. Immediately after hatching, the Fulton condition of juvenile bamboo sharks was significantly different in individuals that experienced future warming and hypercapnia; 30 days after hatching, survival rapidly declined in individuals experiencing both ocean warming and acidification (up to 44%). The RMR of juvenile sharks was also significantly affected by temperature and pH. The impact of low pH on ventilation rates was significant only under the higher thermal scenario. This study highlights the need of experimental-based risk assessments of sharks to climate change. In other words, it is critical to directly assess risk and vulnerability of sharks to ocean acidification and warming, and such effort can ultimately help managers and policy-makers to take proactive measures targeting most endangered species.

  12. Ibuprofen augments bilirubin toxicity in rat cortical neuronal culture.

    Science.gov (United States)

    Berns, Monika; Toennessen, Margit; Koehne, Petra; Altmann, Rodica; Obladen, Michael

    2009-04-01

    Premature infants are at risk for bilirubin-associated brain damage. In cell cultures bilirubin causes neuronal apoptosis and necrosis. Ibuprofen is used to close the ductus arteriosus, and is often given when hyperbilirubinemia is at its maximum. Ibuprofen is known to interfere with bilirubin-albumin binding. We hypothesized that bilirubin toxicity to cultured rat embryonic cortical neurons is augmented by coincubation with ibuprofen. Incubation with ibuprofen above a concentration of 125 microg/mL reduced cell viability, measured by methylthiazole tetrazolium reduction, to 68% of controls (p < 0.05). Lactate dehydrogenase (LDH) release increased from 29 to 38% (p < 0.01). The vehicle solution did not affect cell viability. Coincubation with 10 microM unconjugated bilirubin (UCB)/human serum albumin in a molar ratio of 3:1 and 250 microg/mL ibuprofen caused additional loss of cell viability and increased LDH release (p < 0.01), DNA fragmentation, and activated caspase-3. Preincubation with the pan-caspase inhibitor z-val-ala-asp-fluoromethyl ketone abolished ibuprofen- and UCB-induced DNA fragmentation. The study demonstrates that bilirubin in low concentration of 10 microM reduces neuron viability and ibuprofen increases this effect. Apoptosis is the underlying cell death mechanism.

  13. Relationship between bilirubin free radical and formation of pigment gallstone

    Institute of Scientific and Technical Information of China (English)

    Xiang-Tao Liu; Jian Hu

    2002-01-01

    In this paper, we summarize the main progresses made inour group in the field of the mechanism of pigment gallstoneformation. It was found that after treetment with freeradicals, bilirubin (BR) was changed into free radical itself,and a semiquinone free radical and a superoxide free radicalbound with metal were recognized, which was detected byESR (electron spin resonance). By the meana of NMR(nuclear magnetic resonance) and IR (Infra-red spectra), itwas postulated that bilirubin polymerized through thereaction between the vinyl group and the hydroxyl groupunder the attack of free radicals. It was also found thatbilirubin free radical were liable to calcify in a kinetic study.Because of its chemical properties, bilirubin free radical wasshown to be cytotoxic to hepetocyte, which wasdemonstrated based on the following facts: induction ofphospholipid peroxidation (LPO), leakage of lactatedehydrogenase (LDH) and decrease of glutathione. As tothe mechanism of bilirubin-induced cytotoxicity, it waspostulated that the main target of bilirubin free radical wasthe cell membrane, including phospholipid and membranebound proteins, especially spectrin, a content ofcytoskeleton. Based on the results mentioned above, it wasdeduced that bilirubin free radical is the key factor thatinitiates and promotes the formation of pigment gallstone,which is consistent with other researches in recent years.

  14. Ozone Induced Impairment of Systemic Metabolic Processes: Influence of Prior Ozone Exposure and Metformin Pre-treatment on Aged Wistar Kyoto (WKY) Rats.

    Science.gov (United States)

    SOT2014 Abstract for presentation: March 23-27, 2014; Phoenix, AZ Ozone Induced Impairment of Systemic Metabolic Processes: Influence of Prior Ozone Exposure and Metformin Pre-treatment on Aged Wistar Kyoto (WKY) Rats. V. Bass, D. Andrews, J. Richards, M. Schladweiler, A. Ledb...

  15. Novelty exposure overcomes foot shock-induced spatial-memory impairment by processes of synaptic-tagging in rats

    Science.gov (United States)

    Almaguer-Melian, William; Bergado-Rosado, Jorge; Pavón-Fuentes, Nancy; Alberti-Amador, Esteban; Mercerón-Martínez, Daymara; Frey, Julietta U.

    2012-01-01

    Novelty processing can transform short-term into long-term memory. We propose that this memory-reinforcing effect of novelty could be explained by mechanisms outlined in the “synaptic tagging hypothesis.” Initial short-term memory is sustained by a transient plasticity change at activated synapses and sets synaptic tags. These tags are later able to capture and process the plasticity-related proteins (PRPs), which are required to transform a short-term synaptic change into a long-term one. Novelty is involved in inducing the synthesis of PRPs [Moncada D, et al. (2011) Proc Natl Acad Sci USA 108:12937–12936], which are then captured by the tagged synapses, consolidating memory. In contrast to novelty, stress can impair learning, memory, and synaptic plasticity. Here, we address questions as to whether novelty-induced PRPs are able to prevent the loss of memory caused by stress and if the latter would not interact with the tag-setting process. We used water-maze (WM) training as a spatial learning paradigm to test our hypothesis. Stress was induced by a strong foot shock (FS; 5 × 1 mA, 2 s) applied 5 min after WM training. Our data show that FS reduced long-term but not short-term memory in the WM paradigm. This negative effect on memory consolidation was time- and training-dependent. Interestingly, novelty exposure prevented the stress-induced memory loss of the spatial task and increased BDNF and Arc expression. This rescuing effect was blocked by anisomycin, suggesting that WM-tagged synapses were not reset by FS and were thus able to capture the novelty-induced PRPs, re-establishing FS-impaired long-term memory. PMID:22215603

  16. Cadmium exposure during lactation causes learning and memory-impairment in F1 generation mice: amelioration by quercetin.

    Science.gov (United States)

    Halder, Sumita; Kar, Rajarshi; Galav, Vikas; Mehta, Ashish K; Bhattacharya, Swapan K; Mediratta, Pramod K; Banerjee, Basu D

    2016-01-01

    Cadmium (Cd) is a known pollutant present in the environment at low levels and is reported to affect reproduction in many ways. The present study was undertaken to explore the effect of Cd in F1 generation mice on cognitive parameters, and to further investigate whether quercetin could modulate these effects. In this study, female lactating mice were exposed to cadmium for seven days just after delivery. The new born pups in their adulthood were tested for learning and memory parameters by passive avoidance task and Morris water maze (MWM) test. It was observed that pups exposed to Cd showed significant impairment of memory in step down latency test, which was reversed by quercetin (100 mg/kg). In MWM test for spatial memory, animals exposed to Cd exhibited increased escape latency, which was reversed by quercetin (50 mg/kg) significantly. Quercetin alone (50 and 100 mg/kg) also demonstrated improved spatial memory, and showed improved retention memory in the passive avoidance paradigm at dose 50 mg/kg. On testing oxidative stress parameters, we observed significantly increased malondialdehyde (MDA) levels in brain tissue of Cd-treated mice. Moreover, co-treatment with quercetin (50 mg/kg) and Cd significantly reduced these MDA levels. The other doses (25 and 100 mg/kg) also showed reduction in MDA levels as compared to the group exposed to Cd alone, though the difference was not statistically significant. Hence, this study highlights the possibility of cognitive impairment in adulthood if there is Cd exposure during lactation and oxidative stress could possibly attribute to this effect.

  17. Impaired structural and functional development of cerebellum following gestational exposure of deltamethrin in rats: role of reelin.

    Science.gov (United States)

    Kumar, Kamendra; Patro, Nisha; Patro, Ishan

    2013-07-01

    Reelin is an extracellular matrix molecule that is involved in the normal development of the cerebellar lamination, Bergmann glial fibres alignment, Purkinje cell monolayer arrangement and granule cell migration. In this study, we have examined the effects of maternal exposure of deltamethrin (DLT), a type II pyrethroid insecticide, on the structural and functional development of rat cerebellum during postnatal life. DLT (0.75 mg/kg body weight, intraperitoneally dissolved in dimethylsulphoxide) was administered in timed pregnant rats during two different gestational time periods, i.e. gestational days of 7-10 and 11-14, respectively. In DLT exposed rats, a significant overexpression of reelin was observed in the cells of the external granule cell layer (EGL) and internal granule cell layer along with an ectopic expression of reelin in the EGL as well as in the migrating granule cells just below the EGL, revealing an arrest of granule cell migration in this zone. Mis-orientation and hypertrophy of the Bergmann glial fibres further hampered the journey of the granule cells to their final destination. Possibly reelin overexpression also caused misalignment of the Purkinje cells and inhibited the neurite growth leading to a significant decrease in the spine density, main dendritic length and width of the dendritic arbour. Thus, it is proposed that the DLT exerts its neurotoxic effects possibly via the intracellular accumulation and low release of reelin leading to an impaired granule cell and Purkinje cell migration, inhibition of neurite outgrowth and reduced spine density. Such impaired cerebellar development leads to motor coordination deficits.

  18. Exposure to low-dose bisphenol A impairs meiosis in the rat seminiferous tubule culture model: a physiotoxicogenomic approach.

    Directory of Open Access Journals (Sweden)

    Sazan Ali

    Full Text Available BACKGROUND: Bisphenol A (BPA is one of the most widespread chemicals in the world and is suspected of being responsible for male reproductive impairments. Nevertheless, its molecular mode of action on spermatogenesis is unclear. This work combines physiology and toxicogenomics to identify mechanisms by which BPA affects the timing of meiosis and induces germ-cell abnormalities. METHODS: We used a rat seminiferous tubule culture model mimicking the in vivo adult rat situation. BPA (1 nM and 10 nM was added to the culture medium. Transcriptomic and meiotic studies were performed on the same cultures at the same exposure times (days 8, 14, and 21. Transcriptomics was performed using pangenomic rat microarrays. Immunocytochemistry was conducted with an anti-SCP3 antibody. RESULTS: The gene expression analysis showed that the total number of differentially expressed transcripts was time but not dose dependent. We focused on 120 genes directly involved in the first meiotic prophase, sustaining immunocytochemistry. Sixty-two genes were directly involved in pairing and recombination, some of them with high fold changes. Immunocytochemistry indicated alteration of meiotic progression in the presence of BPA, with increased leptotene and decreased diplotene spermatocyte percentages and partial meiotic arrest at the pachytene checkpoint. Morphological abnormalities were observed at all stages of the meiotic prophase. The prevalent abnormalities were total asynapsis and apoptosis. Transcriptomic analysis sustained immunocytological observations. CONCLUSION: We showed that low doses of BPA alter numerous genes expression, especially those involved in the reproductive system, and severely impair crucial events of the meiotic prophase leading to partial arrest of meiosis in rat seminiferous tubule cultures.

  19. NLRP3 inflammasome activation by mitochondrial reactive oxygen species plays a key role in long-term cognitive impairment induced by paraquat exposure.

    Science.gov (United States)

    Chen, Liuji; Na, Ren; Boldt, Erin; Ran, Qitao

    2015-09-01

    Exposure to environmental toxins such as pesticides is implicated in increasing Alzheimer's disease risk. In this study, we investigated the long-term effects of paraquat exposure on cognition of Alzheimer's disease animal model APP/PS1 mice and wild-type (WT) mice. Our results showed that APP/PS1 mice had exacerbated cognition impairment and elevated Aβ levels at 5 months after paraquat exposure, and that WT mice had cognition impairment at 5 and 16 months after paraquat exposure. In addition, increased mitochondrial oxidative stress and augmented brain inflammation were observed in both paraquat-exposed APP/PS1 mice and WT mice. Interestingly, activation of NLRP3 inflammasome, which triggers inflammation in response to mitochondrial stress, was enhanced in paraquat-exposed mice. Moreover, transgenic mice overexpressing Prdx3, a key enzyme in detoxifying mitochondrial H2O2, had suppressed NLRP3 inflammasome activation, reduced brain inflammation, and attenuated cognition impairment after paraquat exposure. Together, our results indicate that NLRP3 inflammasome activation induced by mitochondrial reactive oxygen species plays a key role in mediating paraquat-induced long-term cognition decline by elevating brain inflammation.

  20. Prenatal alcohol exposure modifies glucocorticoid receptor subcellular distribution in the medial prefrontal cortex and impairs frontal cortex-dependent learning.

    Directory of Open Access Journals (Sweden)

    Andrea M Allan

    Full Text Available Prenatal alcohol exposure (PAE has been shown to impair learning, memory and executive functioning in children. Perseveration, or the failure to respond adaptively to changing contingencies, is a hallmark on neurobehavioral assessment tasks for human fetal alcohol spectrum disorder (FASD. Adaptive responding is predominantly a product of the medial prefrontal cortex (mPFC and is regulated by corticosteroids. In our mouse model of PAE we recently reported deficits in hippocampal formation-dependent learning and memory and a dysregulation of hippocampal formation glucocorticoid receptor (GR subcellular distribution. Here, we examined the effect of PAE on frontal cortical-dependent behavior, as well as mPFC GR subcellular distribution and the levels of regulators of intracellular GR transport. PAE mice displayed significantly reduced response flexibility in a Y-maze reversal learning task. While the levels of total nuclear GR were reduced in PAE mPFC, levels of GR phosphorylated at serines 203, 211 and 226 were not significantly changed. Cytosolic, but not nuclear, MR levels were elevated in the PAE mPFC. The levels of critical GR trafficking proteins, FKBP51, Hsp90, cyclophilin 40, dynamitin and dynein intermediate chain, were altered in PAE mice, in favor of the exclusion of GR from the nucleus, indicating dysregulation of GR trafficking. Our findings suggest that there may be a link between a deficit in GR nuclear localization and frontal cortical learning deficits in prenatal alcohol-exposed mice.

  1. Exposure to runoff from coal-tar-sealed pavement induces genotoxicity and impairment of DNA repair capacity in the RTL-W1 fish liver cell line

    Energy Technology Data Exchange (ETDEWEB)

    Kienzler, Aude, E-mail: aude.kienzler@entpe.fr [Université de Lyon, UMR LEHNA 5023, USC INRA, ENTPE, rue Maurice Audin, Vaulx-en-Velin F-69518 (France); Mahler, Barbara J., E-mail: bjmahler@usgs.gov [U.S. Geological Survey, 1505 Ferguson Lane, Austin, TX 78754 (United States); Van Metre, Peter C., E-mail: pcvanmet@usgs.gov [U.S. Geological Survey, 1505 Ferguson Lane, Austin, TX 78754 (United States); Schweigert, Nathalie [Université de Lyon, UMR LEHNA 5023, USC INRA, ENTPE, rue Maurice Audin, Vaulx-en-Velin F-69518 (France); Devaux, Alain, E-mail: alain.devaux@entpe.fr [Université de Lyon, UMR LEHNA 5023, USC INRA, ENTPE, rue Maurice Audin, Vaulx-en-Velin F-69518 (France); Bony, Sylvie, E-mail: bony@entpe.fr [Université de Lyon, UMR LEHNA 5023, USC INRA, ENTPE, rue Maurice Audin, Vaulx-en-Velin F-69518 (France)

    2015-07-01

    Coal-tar-based (CTB) sealcoat, frequently applied to parking lots and driveways in North America, contains elevated concentrations of polycyclic aromatic hydrocarbons (PAHs) and related compounds. The RTL-W1 fish liver cell line was used to investigate two endpoints (genotoxicity and DNA-repair-capacity impairment) associated with exposure to runoff from asphalt pavement with CTB sealcoat or with an asphalt-based sealcoat hypothesized to contain about 7% CTB sealcoat (AS-blend). Genotoxic potential was assessed by the Formamido pyrimidine glycosylase (Fpg)-modified comet assay for 1:10 and 1:100 dilutions of runoff samples collected from 5 h to 36 d following sealcoat application. DNA-repair capacity was assessed by the base excision repair comet assay for 1:10 dilution of samples collected 26 h and 36 d following application. Both assays were run with and without co-exposure to ultraviolet-A radiation (UVA). With co-exposure to UVA, genotoxic effects were significant for both dilutions of CTB runoff for three of four sample times, and for some samples of AS-blend runoff. Base excision repair was significantly impaired for CTB runoff both with and without UVA exposure, and for AS-blend runoff only in the absence of UVA. This study is the first to investigate the effects of exposure to the complex mixture of chemicals in coal tar on DNA repair capacity. The results indicate that co-exposure to runoff from CT-sealcoated pavement and UVA as much as a month after sealcoat application has the potential to cause genotoxicity and impair DNA repair capacity. - Highlights: • Co-exposure to runoff from coal-tar-sealcoated pavement and UVA caused DNA damage. • Significant genotoxicity occurred with a 1:100 dilution of runoff. • Runoff collected up to 36 d following coal-tar-sealcoat application was genotoxic. • Exposure to runoff from sealed pavement impaired an important DNA repair pathway. • Repair capacity was impaired with a 1:10 dilution of runoff (1:100 not

  2. Blood-brain interfaces and bilirubin-induced neurological diseases.

    Science.gov (United States)

    Ghersi-Egea, J F; Gazzin, S; Strazielle, N

    2009-01-01

    The endothelium of the brain microvessels and the choroid plexus epithelium form highly specialized cellular barriers referred to as blood-brain interfaces through which molecular exchanges take place between the blood and the neuropil or the cerebrospinal fluid, respectively. Within the brain, the ependyma and the pia-glia limitans modulate exchanges between the neuropil and the cerebrospinal fluid. All these interfaces are key elements of neuroprotection and fulfill trophic functions; both properties are critical to harmonious brain development and maturation. By analogy to hepatic bilirubin detoxification pathways, we review the transport and metabolic mechanisms which in all these interfaces may participate in the regulation of bilirubin cerebral bioavailability in physiologic conditions, both in adult and in developing brain. We specifically address the role of ABC and OATP transporters, glutathione-S-transferases, and the potential involvement of glucuronoconjugation and oxidative metabolic pathways. Regulatory mechanisms are explored which are involved in the induction of these pathways and represent potential pharmacological targets to prevent bilirubin accumulation into the brain. We then review the possible alteration of the neuroprotective and trophic barrier functions in the course of bilirubin-induced neurological dysfunctions resulting from hyperbilirubinemia. Finally, we highlight the role of the blood-brain and blood-CSF barriers in regulating the brain biodisposition of candidate drugs for the treatment or prevention of bilirubin-induced brain injury.

  3. Functional polyethersulfone particles for the removal of bilirubin.

    Science.gov (United States)

    Jiang, Xin; Xiang, Tao; Xie, Yi; Wang, Rui; Zhao, Weifeng; Sun, Shudong; Zhao, Chang-Sheng

    2016-02-01

    In this study, polyethersulfone/poly (glycidyl methacrylate) particles are prepared via in situ cross-linked polymerization coupled with a phase inversion technique. The surfaces of these particles are then further modified by grafting amino groups using tetraethylenepentamine, dethylenetriamine, ethylenediamine, or 1,6-hexanediamine for the removal of bilirubin. The particles are characterized by Flourier transform infrared spectroscopy, thermogravimetric analysis, and scanning electron microscopy. Batch adsorption experiments are performed to verify the adsorption capability, and the effect of bilirubin initial concentration, bovine serum albumin concentration, and solution ionic strength on the adsorption is also investigated. In addition, both adsorption kinetic and isotherm models are applied to analyze the adsorption process of bilirubin, and a particle column is used to further study the bilirubin removal ability.To prove that the method was a universal portal to prepare functional particles, polysulfone, polystyrene, and poly(vinylidene fluoride) based functional particles were also prepared and used for the removal of bilirubin. This study and the results indicated that the particles had a great potential to be used in hemoperfusion treatment for hyperbilirubinemia.

  4. Study on Removal of Bilirubin with Magnetic Affinity Separation Technique

    Institute of Scientific and Technical Information of China (English)

    张凤宝; 王淑兰; 徐辉; 张国亮

    2003-01-01

    An affinity adsorbent, Cibacron Blue 3GA immobilized magnetic polyvinyl alcohol (PVA) microspheres was used for bilirubin removal taking the advantage of easy separation of magnetic sorbent from the biosystem.Fe3 O4 superparamagnetic particles was synthesized with hydrothermal reaction of ferrous chloride (FeC12) and ferric chloride (FeCl3). Such magnetic particles are then encapsulated in biocompatible PVA to form magnetic polymer microspheres sized from 2 to 15 nm with hydroxyl groups on its surface. Cibacron Blue 3GA, a dye-ligand, was covalently coupled with the polyvinyl alcohol through the nucleophilic reaction between the chloride of its triazine ring and the hydroxyl groups of PVA molecules under alkaline condition. The affinity adsorbent carried 21.1μmol Cibacron Blue 3GA per gram magnetic polymer microspheres was used to remove unconjugated and conjugated bilirubin from the solution which was composed of bilirubin or bilirubin and protein. After the adsorption, the adsorbent loaded with bilirubin was removed easily in the magnetic field.

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

    Science.gov (United States)

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

    2012-03-01

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

  6. Exposure to runoff from coal-tar-sealed pavement induces genotoxicity and impairment of DNA repair capacity in the RTL-W1 fish liver cell line

    Science.gov (United States)

    Kienzler, Aude; Mahler, Barbara J.; Van Metre, Peter C.; Schweigert, Nathalie; Devaux, Alain; Bony, Sylvie

    2015-01-01

    Coal-tar-based (CTB) sealcoat, frequently applied to parking lots and driveways in North America, contains elevated concentrations of polycyclic aromatic hydrocarbons (PAHs) and related compounds. The RTL-W1 fish liver cell line was used to investigate two endpoints (genotoxicity and DNA-repair-capacity impairment) associated with exposure to runoff from asphalt pavement with CTB sealcoat or with an asphalt-based sealcoat hypothesized to contain about 7% CTB sealcoat (AS-blend). Genotoxic potential was assessed by the Formamido pyrimidine glycosylase (Fpg)-modified comet assay for 1:10 and 1:100 dilutions of runoff samples collected from 5 h to 36 d following sealcoat application. DNA-repair capacity was assessed by the base excision repair comet assay for 1:10 dilution of samples collected 26 h and 36 d following application. Both assays were run with and without co-exposure to ultraviolet-A radiation (UVA). With co-exposure to UVA, genotoxic effects were significant for both dilutions of CTB runoff for three of four sample times, and for some samples of AS-blend runoff. Base excision repair was significantly impaired for CTB runoff both with and without UVA exposure, and for AS-blend runoff only in the absence of UVA. This study is the first to investigate the effects of exposure to the complex mixture of chemicals in coal tar on DNA repair capacity. The results indicate that co-exposure to runoff from CT-sealcoated pavement and UVA as much as a month after sealcoat application has the potential to cause genotoxicity and impair DNA repair capacity.

  7. Differing roles of autophagy in HIV-associated neurocognitive impairment and encephalitis with implications for morphine co-exposure

    Directory of Open Access Journals (Sweden)

    Seth M Dever

    2015-07-01

    Full Text Available We investigated the role of autophagy in HIV-infected subjects with neurocognitive impairment (NCI ± HIV encephalitis (HIVE, many of which had a history of polysubstance abuse/dependence, using post-mortem brain tissues to determine whether differences in autophagy related factors may be more associated with NCI or NCI-encephalitis. Using qRT-PCR, we detected significant differences in gene expression levels with SQSTM1, LAMP1 higher in HIV-infected subjects without NCI while ATG5, SQSTM1 were then lower in HIV infection/NCI and ATG7, SQSTM1 being higher in NCI-HIVE. Immunohistochemical labeling of these autophagy associated proteins (also including Beclin 1 and LC3B in Iba1-postive microglial cells showed generally higher immunoreactivity in the NCI and NCI-HIVE groups with more focal vs. diffuse patterns of expression in the NCI-HIVE group. Furthermore, analysis of microarray data from these same subjects found significantly higher levels of LAMP1 in NCI-HIVE compared to uninfected subjects in the basal ganglia. Finally, we tested the effect of supernatant from HIV-1-infected microglia and HIV-1 Tat protein in combination with morphine on neurons in vitro and found opposing events with both significant inhibition of autophagic flux and reduced dendrite length for morphine and supernatant treatment while Tat and morphine exposure resulted in lower autophagic activity at an earlier time point and higher levels in the later. These results suggest autophagy genes and their corresponding proteins may be differentially regulated at the transcriptional, translational, and post-translational levels in the brain during various stages of the HIV disease and that infected individuals exposed to morphine can experience mixed signaling of autophagic activity which could lead to more severe NCI than those without opioid use.

  8. Developmental exposure to paraquat and maneb can impair cognition, learning and memory in Sprague-Dawley rats.

    Science.gov (United States)

    Li, Bai; He, Xi; Sun, Yan; Li, Baixiang

    2016-10-20

    Paraquat and maneb are identified environmental pollutants. Combined exposure to paraquat and maneb is a latent risk factor for many diseases, particularly those of the central nervous system, including Parkinson's disease and Alzheimer's disease. Hippocampus is the key structure in memory formation and babies are more sensitive to environmental stimuli than adults, so we investigated the neurotoxicity of paraquat and maneb on the hippocampi of rat pups. Female and male Sprague-Dawley rats were mated (female : male = 2 : 1) every night for a week. The gravid rats were randomly divided into three groups (one control and two experimental groups). A mixed solution of paraquat-maneb was administered twice a week by lavage at a dose of 10 or 15 mg kg(-1) bodyweight (containing 30 or 45 mg kg(-1) bodyweight maneb, respectively) from day 6 after pregnancy till ablactation. Maternal weight gain and offspring bodyweights were not affected by the drugs. However, behavioral tests showed that reaction latency and mistake frequency increased after treatment. Intuitively, we found significant changes in the hippocampal neurons in the morphological observation. Taking into account the interaction of the related genes in the cAMP-PKA-CREB pathway, we used a variety of methods to detect the gene and protein levels. Reduced expression of cAMP and related genes and proteins in the hippocampus and serum was also observed. These results indicate that PQ-MB stimulates cAMP to reduce the production of PKA, thus reducing the phosphorylation of CREB and inhibiting the activation of other elements (BDNF, C-JUN, and C-FOS). These changes lead to hippocampal damage and impaired abilities (learning, cognition, and memory). Our results demonstrate that PQ-MB induces hippocampal toxicity in the early life of rats, and they thus provide a theoretical foundation for further investigation of the bathypelagic mechanism involved and measures that can be taken to avoid PQ-MB neurotoxicity.

  9. Effect of pH and temperature on the binding of bilirubin to human erythrocyte membranes

    Indian Academy of Sciences (India)

    H Rashid; Mohammad K Ali; S Tayyab

    2000-06-01

    Effect of pH and temperature on the binding of bilirubin to human erythrocyte membranes was studied by incubating the membranes at different pH and temperatures and determining the bound bilirubin. At all pH values, the amount of membrane-bound bilirubin increased with the increase in bilirubin-to-albumin molar ratios (B/As), being highest at lower pH values in all cases. Further, linear increase in bound bilirubin with the increase in bilirubin concentration in the incubate was observed at a constant B/A and at all pH values. However, the slope value increased with the decrease in pH suggesting more bilirubin binding to membranes at lower pH values. Increase in bilirubin binding at lower pH can be explained on the basis of increased free bilirubin concentration as well as more conversion of bilirubin dianion to monoanion. Temperature dependence of bilirubin binding to membranes was observed within the temperature range of 7°–60°C, showing minimum binding at 27°C and 37°C which increased on either side. Increase in bilirubin binding at temperatures lower than 20°C and higher than 40°C can be ascribed to the change in membrane topography as well as bilirubin-albumin interaction.

  10. Studies on the molecular significance in the interaction of bilirubin with collagen.

    Science.gov (United States)

    Nagarajan, Usharani; Gladstone Christopher, Jayakumar; Chandrasekaran, Bangaru; Jonnalagadda, Raghava Rao; Balachandran, Unni Nair; Kohsaku, Kawakami

    2013-10-01

    The present investigation is aimed to understand the physiological significance of bilirubin interaction with collagen. In human skin, collagen absorbs both free bilirubin and serum bound bilirubin from the human system. Interaction between bilirubin and collagen depends on time, temperature and concentration of bilirubin. There is an increase in the aggregation rate of collagen in the presence of biliruibin. At physiological condition, 125 nM of bilirubin is the maximum concentration absorbed by per mg of collagen molecule. Bilirubin accelerates the lateral growth of collagen fibrils by shifting its rate of nucleation. Moreover, collagen-bilirubin complex exhibit a tendency to undergo adsorption onto the surface of the fibroblast cells, showing detrimental effects on fibroblasts proliferations. Based on the collagen binding assays, the binding of bilirubin to collagen is found to be electrostatic in nature, which confirms binding between the amino acid fragment of α1 (I) region of collagen and carboxyl group of bilirubin. The biotinylated bilirubin derivatives show better binding to α1 (I) chain rather than α2 (I) chains which clearly designates that bilirubin shows greater affinity to α1 chains of collagen. This novel approach directs to reduce the occurrence of bilirubin in hyperbilirubinemia patients.

  11. 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.

    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

  12. 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.

    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

  13. Reduction of phosphorylated synapsin I (ser-553 leads to spatial memory impairment by attenuating GABA release after microwave exposure in Wistar rats.

    Directory of Open Access Journals (Sweden)

    Simo Qiao

    Full Text Available BACKGROUND: Abnormal release of neurotransmitters after microwave exposure can cause learning and memory deficits. This study investigated the mechanism of this effect by exploring the potential role of phosphorylated synapsin I (p-Syn I. METHODS: Wistar rats, rat hippocampal synaptosomes, and differentiated (neuronal PC12 cells were exposed to microwave radiation for 5 min at a mean power density of 30 mW/cm2. Sham group rats, synaptosomes, and cells were otherwise identically treated and acted as controls for all of the following post-exposure analyses. Spatial learning and memory in rats was assessed using the Morris Water Maze (MWM navigation task. The protein expression and presynaptic distribution of p-Syn I and neurotransmitter transporters were examined via western blotting and immunoelectron microscopy, respectively. Levels amino acid neurotransmitter release from rat hippocampal synaptosomes and PC12 cells were measured using high performance liquid chromatograph (HPLC at 6 hours after exposure, with or without synapsin I silencing via shRNA transfection. RESULTS: In the rat experiments, there was a decrease in spatial memory performance after microwave exposure. The expression of p-Syn I (ser-553 was decreased at 3 days post-exposure and elevated at later time points. Vesicular GABA transporter (VGAT was significantly elevated after exposure. The GABA release from synaptosomes was attenuated and p-Syn I (ser-553 and VGAT were both enriched in small clear synaptic vesicles, which abnormally assembled in the presynaptic terminal after exposure. In the PC12 cell experiments, the expression of p-Syn I (ser-553 and GABA release were both attenuated at 6 hours after exposure. Both microwave exposure and p-Syn I silencing reduced GABA release and maximal reduction was found for the combination of the two, indicating a synergetic effect. CONCLUSION: p-Syn I (ser-553 was found to play a key role in the impaired GABA release and cognitive

  14. DECREASED BILIRUBIN TRANSPORT IN THE PERFUSED LIVER OF ENDOTOXEMIC RATS

    NARCIS (Netherlands)

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

    1994-01-01

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

  15. Plasma bilirubin and late graft failure in renal transplant recipients

    NARCIS (Netherlands)

    Deetman, Petronella E.; Zelle, Dorien M.; van der Heide, Jaap J. Homan; Navis, Gerjan J.; Gans, Reinold O. B.; Bakker, Stephan J. L.

    2012-01-01

    Exogenous bilirubin has been shown to protect against oxidative stress in ischemia-reperfusion injury. Oxidative stress has been implicated in the pathophysiology of chronic transplant dysfunction leading to late graft failure after renal transplantation. We prospectively investigated whether high e

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

    Science.gov (United States)

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

    2016-08-16

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

  17. Serum bilirubin levels, polymorphisms and risk for coronary artery disease

    OpenAIRE

    Lingenhel, Arno; Kollerits, Barbara; Johannes P. Schwaiger; Hunt, Steven C.; Gress, Richard; Hopkins, Paul N.; Schoenborn, Veit; Heid, Iris M; Kronenberg, Florian

    2008-01-01

    Serum bilirubin levels, UGT1A1 polymorphisms and risk for coronary artery disease correspondence: Corresponding author. Tel.: +43 512 9003 70560; fax: +43 512 9003 73560. (Kronenberg, Florian) (Kronenberg, Florian) Division of Genetic Epidemiology; Department of Medical Genetics, Molecular and Clinical Pharmacology; Innsbruck Medical University - AUSTRIA (Lingenhel, Arno) Division of Genetic Epidemiology; Depa...

  18. RAPID ASSOCIATION OF UNCONJUGATED BILIRUBIN WITH AMORPHOUS CALCIUM-PHOSPHATE

    NARCIS (Netherlands)

    VANDERVEERE, CN; SHOEMAKER, B; VANDERMEER, R; GROEN, AK; JANSEN, PLM; ELFERINK, RPJO

    1995-01-01

    The association of unconjugated bilirubin (UCB) with amorphous calcium phosphate was studied in vitro. To this end UCB, solubilized in different micellar bile salt solutions, was incubated with freshly prepared calcium phosphate precipitate. It was demonstrated that amorphous calcium phosphate (ACP)

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

    DEFF Research Database (Denmark)

    Honoré, B; Frandsen, P C

    1986-01-01

    Light-absorption, c.d. and fluorescence of the bilirubin-albumin complex were investigated at extreme alkaline pH. Above pH 11.1 albumin binds the bilirubin molecule, twisted oppositely to the configuration at more neutral pH. On the basis of light-absorption it is shown that two alkaline...... between tryptophan-214 and bilirubin, and partly exposing the liganded bilirubin to the solvent. Udgivelsesdato: 1986-Jun-1...

  20. Clinical Significance of Serum Bilirubin Detection of Patient with Coronary Heart Disease

    Institute of Scientific and Technical Information of China (English)

    TAO Li; LUO Rui; ZHUANG Diankui

    2004-01-01

    Objective To explore the relation between serum bilirubin and coronary heart disease.Methods Compare the level of serum bilirubin among patients with coronary heart disease, patients with other disease and normal persons. Results The level of serum bilirubin of patients with coronary heart disease is higher than that of normal persons. Conclusion The reduction of density of serum bilirubin is one of the independent risk factors of coronary heart disease.

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

    Science.gov (United States)

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

    2012-07-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-07-15

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

  3. Impaired brain development in the rat following prenatal exposure to methylazoxymethanol acetate at gestational day 17 and neurotrophin distribution

    NARCIS (Netherlands)

    Fiore, M; Grace, AA; Korf, J; Stampachiacchiere, B; Aloe, L

    2004-01-01

    Several neuropsychiatric disorders, including schizophrenia, are the consequence of a disrupted development of the CNS. Accordingly, intrauterine exposure to toxins may increase the risk for psychopathology. We investigated whether prenatal exposure of rats to the neurotoxin methylaxoxymethanol acet

  4. Ultrafine particulate matter exposure in vitro impairs vasorelaxant response in superoxide dismutase 2 deficient and aged murine aortic rings

    Science.gov (United States)

    Epidemiological studies positively associate exposure to inhaled ultrafine particulate matter (UFPM) and adverse cardiovascular events. PM-induced oxidative stress is believed to be a key mechanism contributing to the adverse short-term vascular effects of air pollution exposure....

  5. Intestinal excretion of unconjugated bilirubin in man and rats with inherited unconjugated hyperbilirubinemia

    NARCIS (Netherlands)

    Kotal, P; VanderVeere, CN; Sinaasappel, M; Elferink, RO; Vitek, L; Brodanova, M; Jansen, PLM; Fevery, J

    1997-01-01

    Patients with Crigler-Najjar syndrome and Gunn rats cannot form bilirubin glucuronides owing to a lack of bilirubin UDP-glucuronosyltransferase activity. Because increased serum and tissue bilirubin levels remain constant, an alternative excretory route has to substitute for this deficiency. Gunn ra

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

    Science.gov (United States)

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

    2011-01-01

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

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

    Science.gov (United States)

    Mustafa, Mir Faisal; Bano, Bilqees

    2014-05-01

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

  8. Whole body exposure to 2.4 GHz WIFI signals: effects on cognitive impairment in adult triple transgenic mouse models of Alzheimer's disease (3xTg-AD).

    Science.gov (United States)

    Banaceur, Sana; Banasr, Sihem; Sakly, Mohsen; Abdelmelek, Hafedh

    2013-03-01

    The present investigation aimed at evaluating the effects of long-term exposure to WIFI type radiofrequency (RF) signals (2.40 GHz), two hours per day during one month at a Specific Absorption Rate (SAR) of 1.60 W/kg. The effects of RF exposure were studied on wildtype mice and triple transgenic mice (3xTg-AD) destined to develop Alzheimer's-like cognitive impairment. Mice were divided into four groups: two sham groups (WT, TG; n=7) and two exposed groups (WTS, TGS; n=7). The cognitive interference task used in this study was designed from an analogous human cognitive interference task including the Flex field activity system test, the two-compartment box test and the Barnes maze test. Our data demonstrate for the first time that RF improves cognitive behavior of 3xTg-AD mice. We conclude that RF exposure may represent an effective memory-enhancing approach in Alzheimer's disease.

  9. Heme oxygenase-1-derived bilirubin protects endothelial cells against high glucose-induced damage.

    Science.gov (United States)

    He, Meihua; Nitti, Mariapaola; Piras, Sabrina; Furfaro, Anna Lisa; Traverso, Nicola; Pronzato, Maria Adelaide; Mann, Giovanni E

    2015-12-01

    Hyperglycemia and diabetes are associated with endothelial cell dysfunction arising from enhanced oxidative injury, leading to the progression of diabetic vascular pathologies. The redox-sensitive transcription factor nuclear factor-E2-related factor 2 (Nrf2) is a master regulator of antioxidant genes, such as heme oxygenase-1 (HO-1), involved in cellular defenses against oxidative stress. We have investigated the pathways involved in high glucose-induced activation of HO-1 in endothelial cells and examined the molecular mechanisms underlying cytoprotection. Elevated d-glucose increased intracellular generation of reactive oxygen species (ROS), leading to nuclear translocation of Nrf2 and HO-1 expression in bovine aortic endothelial cells, with no changes in cell viability. Superoxide scavenging and inhibition of endothelial nitric oxide synthase (eNOS) abrogated upregulation of HO-1 expression by elevated glucose. Inhibition of HO-1 increased the sensitivity of endothelial cells to high glucose-mediated damage, while addition of bilirubin restored cell viability. Our findings establish that exposure of endothelial cells to high glucose leads to activation of endogenous antioxidant defense genes via the Nrf2/ARE pathway. Upregulation of HO-1 provides cytoprotection against high glucose-induced oxidative stress through the antioxidant properties of bilirubin. Modulation of the Nrf2 pathway in the early stages of diabetes may thus protect against sustained damage by hyperglycemia during progression of the disease.

  10. GESTATIONAL AND LACTATIONAL EXPOSURE TO PROPYLTHIOURACIL INDUCES HYPOTHYROIDISM AND IMPAIRS SYNAPTIC TRANSMISSION AND PLASTICITY IN AREA CA1 OF HIPPOCAMPUS.

    Science.gov (United States)

    Although severe developmental hypothyroidism leads to stunted growth, alterations in hippocampal structure, and impaired performance on a variety of behavioral learning tasks, the impact of milder forms of hypothyroidism has not been adequately assessed. Preliminary reports of ...

  11. Perinatal exposure to bisphenol-A impairs spatial memory through upregulation of neurexin1 and neuroligin3 expression in male mouse brain.

    Directory of Open Access Journals (Sweden)

    Dhiraj Kumar

    Full Text Available Bisphenol-A (BPA, a well known endocrine disruptor, impairs learning and memory in rodents. However, the underlying molecular mechanism of BPA induced impairment in learning and memory is not well known. As synaptic plasticity is the cellular basis of memory, the present study investigated the effect of perinatal exposure to BPA on the expression of synaptic proteins neurexin1 (Nrxn1 and neuroligin3 (Nlgn3, dendritic spine density and spatial memory in postnatal male mice. The pregnant mice were orally administered BPA (50 µg/kgbw/d from gestation day (GD 7 to postnatal day (PND 21 and sesame oil was used as a vehicle control. In Morris water maze (MWM test, BPA extended the escape latency time to locate the hidden platform in 8 weeks male mice. RT-PCR and Immunoblotting results showed significant upregulation of Nrxn1 and Nlgn3 expression in both cerebral cortex and hippocampus of 3 and 8 weeks male mice. This was further substantiated by in-situ hybridization and immunofluorescence techniques. BPA also significantly increased the density of dendritic spines in both regions, as analyzed by rapid Golgi staining. Thus our data suggest that perinatal exposure to BPA impairs spatial memory through upregulation of expression of synaptic proteins Nrxn1 and Nlgn3 and increased dendritic spine density in cerebral cortex and hippocampus of postnatal male mice.

  12. Microwave Exposure Impairs Synaptic Plasticity in the Rat Hippocampus and PC12 Cells through Over-activation of the NMDA Receptor Signaling Pathway

    Institute of Scientific and Technical Information of China (English)

    XIONG Lu; DONG Ji; YAO Bin Wei; ZHAO Li; PENG Rui Yun; SUN Cheng Feng; ZHANG Jing; GAO Ya Bing; WANG Li Feng; ZUO Hong Yan; WANG Shui Ming; ZHOU Hong Mei; XU Xin Ping

    2015-01-01

    Objective The aim of this study is to investigate whether microwave exposure would affect the N-methyl-D-aspartate receptor (NMDAR) signaling pathway to establish whether this plays a role in synaptic plasticity impairment. Methods 48 male Wistar rats were exposed to 30 mW/cm² microwave for 10 min every other day for three times. Hippocampal structure was observed through H&E staining and transmission electron microscope. PC12 cells were exposed to 30 mW/cm² microwave for 5 min and the synapse morphology was visualized with scanning electron microscope and atomic force microscope. The release of amino acid neurotransmitters and calcium influx were detected. The expressions of several key NMDAR signaling molecules were evaluated. Results Microwave exposure caused injury in rat hippocampal structure and PC12 cells, especially the structure and quantity of synapses. The ratio of glutamic acid and gamma-aminobutyric acid neurotransmitters was increased and the intracellular calcium level was elevated in PC12 cells. A significant change in NMDAR subunits (NR1, NR2A, and NR2B) and related signaling molecules (Ca2+/calmodulin-dependent kinase II gamma and phosphorylated cAMP-response element binding protein) were examined. Conclusion 30 mW/cm² microwave exposure resulted in alterations of synaptic structure, amino acid neurotransmitter release and calcium influx. NMDAR signaling molecules were closely associated with impaired synaptic plasticity.

  13. Bilirubin exerts pro-angiogenic property through Akt-eNOS-dependent pathway.

    Science.gov (United States)

    Ikeda, Yasumasa; Hamano, Hirofumi; Satoh, Akiho; Horinouchi, Yuya; Izawa-Ishizawa, Yuki; Kihira, Yoshitaka; Ishizawa, Keisuke; Aihara, Ken-Ichi; Tsuchiya, Koichiro; Tamaki, Toshiaki

    2015-11-01

    Low serum bilirubin levels are associated with the risk of cardiovascular diseases including peripheral artery disease. Bilirubin is known to exert its property such as antioxidant effect or the enhancement of flow-mediated vasodilation, however, bilirubin action on angiogenesis remains unclear. To investigate the molecular mechanism of bilirubin on angiogenic effect, we first employed C57BL/6J mice with unilateral hindlimb ischemia surgery and divided the mice into two groups (vehicle-treated group and bilirubin-treated group). The analysis of laser speckle blood flow demonstrated the enhancement of blood flow recovery in response to ischemia of mice with bilirubin treatment. The density of capillaries was significantly higher in ischemic-adductor muscles of bilirubin-treated mice. The phosphorylated levels of endothelial nitric oxide synthase (eNOS) and Akt were increased in ischemic skeletal muscles of mice with bilirubin treatment compared with vehicle treatment. In in vitro experiments by using human aortic endothelial cells, bilirubin augmented eNOS and Akt phosphorylation, cell proliferation, cell migration and tube formation. These bilirubin actions on endothelial cell activation were inhibited by LY294002, a phosphatidylinositol 3-kinase inhibitor. In conclusion, bilirubin promotes angiogenesis through endothelial cells activation via Akt-eNOS-dependent manner.

  14. Determination of bilirubin by thermal lens spectrometry and studies of its transport into hepatic cells

    Science.gov (United States)

    Margon, A.; Terdoslavich, M.; Cocolo, A.; Decorti, G.; Passamonti, S.; Franko, M.

    2005-06-01

    The liver is responsible for clearance of bilirubin, the end product of heme catabolism, from the bloodstream. The main aim of our investigation was to determine the role of the carrier protein bilitranslocase in bilirubin uptake into the liver. Our experiments consisted of exposing cell cultures to bilirubin solutions under different conditions and measuring the uptake of bilirubin into the cells. However, since bilirubin is only slightly soluble in aqueous solution (pH 7.4), we had to use bilirubin concentrations that are far below the limit of detection of the commonly used techniques (e.g. LOD for HPLC with UV-Vis detection \\cong 10 μM). TLS showed up to be a suitable technique for investigation of bilirubin uptake with an LOD of 2 nM. Under basal conditions, bilirubin uptake did not occur. However, increase of cytosolic NADH due to catabolism of specific substrates (e.g. lactate or ethanol) seemed to trigger bilirubin uptake. Furthermore, bilirubin uptake was completely inhibited by addition of specific anti-bilitranslocase antibodies. We can thus infer that, under these conditions, bilitranslocase is the main bilirubin transporter.

  15. A New Bilirubin Concentration Detection Method by Light Reflection

    CERN Document Server

    Subasilar, B

    1999-01-01

    A new and simple method of blood bilirubin detection through light reflection from skin is developed. The basic improvement over the existing methods is in the design of the light emitter and detector geometry which facilitates a two-stream plane parallel homogenous medium solution to the emitting-scatterig radiative transfer equation. The forward peak in the scattering phase function that is characteristic of water droplets and water filled media is accounted for through a proper method named delta-Eddington approximation.

  16. The Relationship of the Anti-Oxidant Bilirubin with Free Thyroxine Is Modified by Insulin Resistance in Euthyroid Subjects

    NARCIS (Netherlands)

    Deetman, Petronella E.; Bakker, Stephan J. L.; Kwakernaak, Arjan J.; Navis, Gerjan; Dullaart, Robin P. F.

    2014-01-01

    Background: The strong anti-oxidative properties of bilirubin largely explain its cardioprotective effects. Insulin resistance is featured by low circulating bilirubin. Thyroid hormone affects both bilirubin generation and its biliary transport, but it is unknown whether circulating bilirubin is ass

  17. Bilirubin: an endogenous molecule with antiviral activity in vitro.

    Directory of Open Access Journals (Sweden)

    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.

  18. Molecularly Imprinted Quartz Crystal Microbalance Sensor (QCM for Bilirubin Detection

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    Çiğdem Çiçek

    2016-11-01

    Full Text Available This study aims the preparation of a QCM sensor for the detection of bilirubin in human plasma. Bilirubin-imprinted poly-(2-hydroxyethyl methacrylate-N-methacryloyl-l-tryptophan methyl ester (PHEMATrp nanofilm (MIP on the gold surface of a QCM chip was synthesized by the molecular imprinting technique. Meanwhile, the non-imprinted PHEMATrp (NIP nanofilm was synthesized by the same experimental technique to examine the imprinting effect. Characterization of MIP and NIP nanofilms on the QCM chip surface was achieved by atomic force microscopy (AFM, ellipsometry, Fourier transform infrared spectrophotometry-attenuated total reflectance (FTIR-ATR and contact angle measurements (CA. The observations indicated that the nanofilm was almost in a monolayer. Thereinafter, the imprinted and the non-imprinted QCM chips were connected to the QCM system to investigate kinetic and affinity properties. In order to examine the selectivity of the MIP-PHEMATrp nanofilm, competitive adsorption of bilirubin with cholesterol and estradiol was performed. Limit of detection (LOD and limit of quantitation (LOQ values were calculated as 0.45 μg/mL and 0.9 μg/mL, respectively.

  19. Spectroscopic studies on the interaction of bilirubin with liver cystatin.

    Science.gov (United States)

    Shah, Aaliya; Bano, Bilqees

    2011-02-01

    Studies on the role of endogenous metabolites such as bilirubin and their interactions with biomolecules have attracted considerable attention over the past several years. In this work, the interaction of bilirubin (BR) with purified goat liver cystatin (LC) was studied using fluorescence and ultraviolet (UV) spectroscopy. The fluorescence data proved that the fluorescence quenching of liver cystatin by BR was the result of BR-cystatin complex formation. Stern-Volmer analysis of fluorescence quenching data showed the binding constant to be 9.27 x 10⁴ M⁻¹ and the number of binding sites to be close to unity. The conformation of the BR-cystatin complex was found to change upon varying the pH of the complex. The BR-cystatin complex was found to have reduced papain inhibitory activity. Photo-illumination of BR-cystatin complex causes perturbation in the micro-environment of goat liver cystatin as indicated by red-shift. This report summarizes our research efforts to reveal the mechanism of interaction of bilirubin with liver cystatin.

  20. Long-term exposure to arsenic affects head kidney and impairs humoral immune responses of Clarias batrachus

    Energy Technology Data Exchange (ETDEWEB)

    Ghosh, Debabrata [Immunobiology Laboratory, School of Life Sciences, Visva-Bharati University, Santiniketan 731235 (India); Datta, Soma [Immunobiology Laboratory, School of Life Sciences, Visva-Bharati University, Santiniketan 731235 (India); Bhattacharya, Shelley [Environmental Toxicology Laboratory, School of Life Sciences, Visva-Bharati University, Santiniketan 731235 (India); Mazumder, Shibnath [Immunobiology Laboratory, School of Life Sciences, Visva-Bharati University, Santiniketan 731235 (India)]. E-mail: shibnath1@yahoo.co.in

    2007-02-15

    The present study was aimed at determining the effects of long-term arsenic exposure on the head kidney (HK) and ensuing humoral immune responses in Clarias batrachus L. Long-term exposure (150 days) to non-lethal concentrations of arsenic (42.42 {mu}M) resulted in significant time-dependent alterations in HK cell number eventually affecting the HK somatic index. Prolonged exposure to arsenic also suppressed HK-B cell proliferation and led to significant reduction in serum immunoglobulin levels and antigen-specific serum bacterial agglutinin titers. A decline in the number of antigen-specific plaque-forming cells with duration of arsenic exposure was noted in the HK. Enzyme linked immunosorbent assays further revealed that arsenic exposure inhibited the release of 'IL-4 like factors' from HK-T cells. Histological studies documented time-dependent changes in the structure and cellular composition of HK characterized by extensive lymphocytopenia, decrease in melano-macrophage population and hemosiderin accumulation. From exposure-challenge studies with Aeromonas hydrophila it was evident that pathogens could efficiently disseminate and colonize distant host tissues in the exposed fish. Moreover, the ability to decrease the pathogen load was also significantly reduced in the arsenic-exposed fish. Thus long-term exposure to non-lethal concentrations of arsenic affects HK and interferes with the humoral immune system of C. batrachus rendering them immunocompromised and susceptible to pathogenic challenge.

  1. Physiological, molecular, and cellular mechanisms of impaired seawater tolerance following exposure of Atlantic salmon, Salmo salar, smolts to acid and aluminum

    Energy Technology Data Exchange (ETDEWEB)

    Monette, Michelle Y., E-mail: michelle.monette@yale.edu [Organismic and Evolutionary Biology Program, University of Massachusetts, Amherst, MA 01003 (United States); USGS, Conte Anadromous Fish Research Center, Turners Falls, MA 01376 (United States); Yada, Takashi [Freshwater Fisheries Research Department, National Research Institute of Fisheries Science, Nikko (Japan); Matey, Victoria [Department of Biology, San Diego State University, San Diego, CA 92182 (United States); McCormick, Stephen D. [Organismic and Evolutionary Biology Program, University of Massachusetts, Amherst, MA 01003 (United States); USGS, Conte Anadromous Fish Research Center, Turners Falls, MA 01376 (United States)

    2010-08-01

    We examined the physiological, molecular, and cellular mechanisms of impaired ion regulation in Atlantic salmon, Salmo salar, smolts following acute acid and aluminum (Al) exposure. Smolts were exposed to: control (pH 6.5, 3.4 {mu}g l{sup -1} Al), acid and low Al (LAl: pH 5.4, 11 {mu}g l{sup -1} Al), acid and moderate Al (MAl: pH 5.3, 42 {mu}g l{sup -1} Al), and acid and high Al (HAl: pH 5.4, 56 {mu}g l{sup -1} Al) for two and six days. At each time-point, smolts were sampled directly from freshwater treatment tanks and after a 24 h seawater challenge. Exposure to acid/MAl and acid/HAl led to accumulation of gill Al, substantial alterations in gill morphology, reduced gill Na{sup +}/K{sup +}-ATPase (NKA) activity, and impaired ion regulation in both freshwater and seawater. Exposure to acid/MAl for six days also led to a decrease in gill mRNA expression of the apical Cl{sup -} channel (cystic fibrosis transmembrane conductance regulator I), increased apoptosis upon seawater exposure, an increase in the surface expression of mitochondria-rich cells (MRCs) within the filament epithelium of the gill, but reduced abundance of gill NKA-positive MRCs. By contrast, smolts exposed to acid and the lowest Al concentration exhibited minor gill Al accumulation, slight morphological modifications in the gill, and impaired seawater tolerance in the absence of a detectable effect on freshwater ion regulation. These impacts were accompanied by decreased cell proliferation, a slight increase in the surface expression of MRCs within the filament epithelium, but no impact on gill apoptosis or total MRC abundance was observed. However, MRCs in the gills of smolts exposed to acid/LAl exhibited morphological alterations including decreased size, staining intensity, and shape factor. We demonstrate that the seawater tolerance of Atlantic salmon smolts is extremely sensitive to acute exposure to acid and low levels of Al, and that the mechanisms underlying this depend on the time

  2. 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

  3. Prenatal melamine exposure impairs spatial cognition and hippocampal synaptic plasticity by presynaptic and postsynaptic inhibition of glutamatergic transmission in adolescent offspring.

    Science.gov (United States)

    An, Lei; Sun, Wei

    2017-03-05

    Our previous studies showed that prenatal melamine exposure (PME) could impair spatial cognition and hippocampal long-term potentiation (LTP). More importantly, the synaptic dysfunction induced by PME was associated with the probability of presynaptic glutamate release. Considering the crucial role of the other form of synaptic plasticity, long-term depression (LTD), in some types of learning and memory process, the aim of present study was to investigate if the hippocampal LTD and cognitive flexibility were affected. And then we attempted to explore the underlying mechanism. The animal model was produced by melamine exposure throughout gestational period with 400mg/kg bodyweight, the male offspring rats were used in the study. Morris water maze (MWM) test was performed, and then LTD was recorded from Schaffer collaterals to CA1 region in the hippocampus. Behavioral test showed that learning, reference memory and re-acquisition learning abilities were impaired significantly by PME. The field excitatory postsynaptic potentials (fEPSPs) slopes of LTD were significantly higher after PME. Furthermore, the data of whole-cell patch-clamp experiments showed that PME markedly diminished the frequencies of spontaneous EPSCs (sEPSCs) and simultaneously reduced the amplitude of sEPSCs. In conclusion, PME inhibited glutamate transmission presynaptically and postsynaptically which could contribute importantly to the depressed hippocampal synaptic plasticity and further induced cognitive deficits in MWM tests.

  4. Exposure to cows is not associated with diarrhoea or impaired child growth in rural Odisha, India: a cohort study.

    Science.gov (United States)

    Schmidt, W-P; Boisson, S; Routray, P; Bell, M; Cameron, M; Torondel, B; Clasen, T

    2016-01-01

    Exposure to animal livestock has been linked to zoonotic transmission, especially of gastrointestinal pathogens. Exposure to animals may contribute to chronic asymptomatic intestinal infection, environmental enteropathy and child under-nutrition in low-income settings. We conducted a cohort study to explore the effect of exposure to cows on growth and endemic diarrhoea in children aged <5 years in a rural, low-income setting in the Indian state of Odisha. The study enrolled 1992 households with 2739 children. Height measurements were available for 824 children. Exposure to cows was measured as (1) the presence of a cowshed within or outside the compound, (2) the number of cows owned by a household, and (3) the number of cowsheds located within 50 m of a household. In a sub-study of 518 households, fly traps were used to count the number of synanthropic flies that may act as vectors for gastrointestinal pathogens. We found no evidence that environmental exposure to cows contributes to growth deficiency in children in rural India, neither directly by affecting growth, nor indirectly by increasing the risk of diarrhoea. We found no strong evidence that the presence of a cowshed increased the number synanthropic flies in households.

  5. Age-related impairment of long-term depression in area CA1 and dentate gyrus of rat hippocampus following developmental lead exposure in vitro.

    Science.gov (United States)

    Sui, L; Ge, S Y; Ruan, D Y; Chen, J T; Xu, Y Z; Wang, M

    2000-01-01

    Chronic developmental lead exposure is known to be associated with cognitive dysfunction in children. Impairment of the induction of long-term depression (LTD) has been reported in area CA1 and dentate gyrus (DG) of rat hippocampus following chronic lead exposure. The present study was carried out to investigate age-related alterations of LTD in area CA1 and DG of rat hippocampus following developmental lead exposure in vitro. Neonatal Wistar rats were exposed to lead from parturition to weaning via milk of dams drinking 0.2% lead acetate solution. Field excitatory postsynaptic potentials (EPSPs) were recorded in hippocampal slices at various postnatal ages: postnatal day (PND) 17-23, 27-33, and 57-63. Following low-frequency stimulation (LFS, 900 pulses/1 Hz), the average magnitude of LTD is age related. In the controls, LTD magnitude in area CA1 decreased with age, whereas in DG it increased with age. In the lead-exposed groups, the magnitude of LTD declined during development in both area CA1 and DG. The differences of LTD magnitude between the control and lead-exposed rats were 27.26 +/- 9.15% (PND 17-23), 21.59 +/- 12.93% (PND 27-33), and 16.96 +/- 9.33% (PND 57-63) in area CA1, and were 6.95 +/- 9.26%, 17.60 +/- 3.91%, and 33.63 +/- 10.47% in DG, respectively. These results demonstrated that the lead-induced impairment of LTD magnitude was an age-related decline in area CA1 and an age-related increase in area DG of rat hippocampus. Published by Elsevier Science Inc.

  6. Association between flavonoid-rich fruit and vegetable consumption and total serum bilirubin.

    Science.gov (United States)

    Loprinzi, Paul D; Mahoney, Sara E

    2015-03-01

    Emerging work demonstrates that serum bilirubin is a novel biomarker implicated in cardiovascular and metabolic diseases. However, we have a limited understanding of the influence of flavonoid-rich fruit and vegetable consumption on bilirubin levels, which was the purpose of this study. Data from the 2003 to 2006 National Health and Nutrition Examination survey were used (n = 1783; 18-85 years of age), with analyses performed in 2014. Total serum bilirubin was measured from a blood sample. Using a food frequency questionnaire (FFQ), a flavonoid index variable was created summing the frequency of consumption of flavonoid-rich foods. After adjustments, greater consumption of flavonoid-rich fruits and vegetables was positively associated with bilirubin levels. Our findings suggest an association between flavonoid-rich fruit and vegetable consumption and bilirubin levels. If confirmed by prospective and experimental studies, then regular consumption of flavonoid-rich fruits and vegetables should be promoted to increase levels of bilirubin.

  7. Influence of pre-exposure to morphine on cannabinoid-induced impairment of spatial memory in male rats.

    Science.gov (United States)

    Farahmandfar, Maryam; Kadivar, Mehdi; Naghdi, Nasser; Choopani, Samira; Zarrindast, Mohammad-Reza

    2013-11-01

    In the present study, we investigated the effects of repeated morphine pre-treatment on impairment of spatial memory acquisition induced by intra dorsal hippocampus (intra-CA1) administration of the non-selective cannabinoid CB1/CB2 receptor agonist, WIN55,212-2 in adult male rats. 2-day version of Morris water maze task has been used for the assessment of spatial memory. On the training day, rats were trained by a single training session of eight trials and 24 h later a probe trial test consist of 60s free swim period without a platform and the visible test was administered. Animals received pre-treatment subcutaneous (s.c.) injections of morphine, once daily for three days followed by five days drug-free treatment before training trials. The results indicated that bilateral pre-training intra-CA1 infusions of WIN55,212-2 (0.25 and 0.5 μg/rat) impaired acquisition of spatial memory on the training and test day. The amnesic effect of WIN55, 212-2 (0.5 μg/rat) was prevented in rats previously injected with morphine (20 mg/kg/day × 3 days, s.c.). Improvement in spatial memory acquisition in morphine-pretreated rats was inhibited by once daily administration of naloxone (1 and 2 mg/kg, s.c.) 15 min prior to injection of morphine for three days. The results suggest that sub-chronic morphine treatment may produced sensitization to cannabinoids, which in turn reversed the impairment of spatial memory acquisition induced by WIN55,212-2 and mu- opioid receptors may play an important role in this effect.

  8. Exposure to activity based anorexia impairs contextual learning in weight-restored rats without affecting spatial learning, taste, anxiety, or dietary-fat preference

    Science.gov (United States)

    Boersma, Gretha J.; Treesukosol, Yada; Cordner, Zachary A.; Kastelein, Anneke; Choi, Pique; Moran, Timothy H.; Tamashiro, Kellie L.

    2016-01-01

    Relapse rates are high amongst cases of Anorexia Nervosa (AN) suggesting that some alterations induced by AN may remain after weight restoration. Objective To study the consequences of AN without confounds of environmental variability, a rodent model of activity based anorexia (ABA) can be employed. We hypothesized that exposure to ABA during adolescence may have long-term consequences in taste function, cognition, and anxiety-like behavior after weight restoration. Methods To test this hypothesis we exposed adolescent female rats to ABA (1.5 hrs food access, combined with voluntary running wheel access) and compared their behavior to that of control rats after weight restoration was achieved. The rats were tested for learning /memory, anxiety, food preference and taste in a set of behavioral tests performed during the light period. Results Our data show that ABA exposure leads to reduced performance during the novel object recognition task, a test for contextual learning, without altering performance in the novel place recognition task or the Barnes maze, both tasks that test spatial learning. Furthermore, we do not observe alterations in unconditioned lick responses to sucrose nor quinine (described by humans as “sweet” and “bitter” respectively). Nor did we find alterations in anxiety-like behavior during an elevated plus maze or an open field test. Finally, preference for a diet high in fat was not altered. Discussion Overall our data suggest that ABA exposure during adolescence impairs contextual learning in adulthood without altering spatial leaning, taste, anxiety, or fat preference. PMID:26711541

  9. High preoperative bilirubin values protect against reperfusion injury after live donor liver transplantation.

    Science.gov (United States)

    Spetzler, Vinzent N; Goldaracena, Nicolas; Kaths, Johann M; Marquez, Max; Selzner, Nazia; Cattral, Mark S; Greig, Paul D; Lilly, Les; McGilvray, Ian D; Levy, Gary A; Ghanekar, Anand; Renner, Eberhard L; Grant, David R; Selzner, Markus

    2015-11-01

    Heme Oxygenase-1 and its product biliverdin/bilirubin have been demonstrated to protect against ischemia/reperfusion injury (IRI). We investigated whether increased preoperative bilirubin values of transplant recipients decrease IRI. Preoperative bilirubin levels of live donor liver recipients were correlated to postoperative liver transaminase as a marker of IRI. Additionally, two recipient groups with pretransplant bilirubin levels >24 μmol/l (n = 348) and ≤24 μmol/l (n = 118) were compared. Post-transplant liver function, complications, length of hospital stay, and patient and graft survival were assessed. Preoperative bilirubin levels were negatively correlated to the postoperative increase in transaminases suggesting a protective effect against IRI. The maximal rise of ALT after transplantation in high versus low bilirubin patients was 288 (-210-2457) U/l vs. 375 (-11-2102) U/l, P = 0.006. Bilirubin remained a significant determining factor in a multivariate linear regression analysis. The MELD score and its individual components as a marker of severity of chronic liver disease were significantly higher in the high versus low bilirubin group (P bilirubin levels of liver recipients before live donor transplantation is associated with decreased postoperative IRI.

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

    Science.gov (United States)

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

    2015-05-28

    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.

  11. The kinetics of oxidation of bilirubin and ascorbic acid in solution

    Science.gov (United States)

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

    2012-07-01

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

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

    Science.gov (United States)

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

    2015-05-01

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

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

    Science.gov (United States)

    2010-04-01

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

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

    Science.gov (United States)

    2010-04-01

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

  15. Acute but not chronic ethanol exposure impairs retinol oxidation in the small and large intestine of the rat

    DEFF Research Database (Denmark)

    Parlesak, Alexandr; Ellendt, K.; Lindros, K.;

    2005-01-01

    BACKGROUND AND AIM: Ethanol has been shown to inhibit retinol oxidation at the level of alcohol dehydrogenase in liver and colon but not previously in the small intestine. In the present study we investigated how chronic alcohol feeding and acute ethanol exposure affects retinol dehydrogenase...... activity in the colon and small intestine of the rat. METHODS: Rats were fed ethanol in a liquid diet for six weeks. Control rats received a similar diet but with ethanol isocalorically replaced by carbohydrates. Retinol dehydrogenase was analyzed from cell cytosol samples from the small and the large...... higher, respectively). While chronic alcohol feeding did not affect these parameters, acute ethanol exposure reduced V(max) and V(max)/K(m) dose-dependently (p retinol...

  16. Bilirubin as an antioxidant: kinetic studies of the reaction of bilirubin with peroxyl radicals in solution, micelles, and lipid bilayers.

    Science.gov (United States)

    Hatfield, Gillian L; Barclay, L Ross C

    2004-05-13

    Bilirubin (BR) showed very weak antioxidant activity in a nonpolar medium of styrene or cumene in chlorobenzene. In contrast, BR exhibited strong antioxidant activity in polar media such as aqueous lipid bilayers or SDS micelles/methyl linoleate (pH 7.4), where the rate with peroxyl radicals, k(inh) = 5.0 x 10(4) M(-)(1) s(-)(1), was comparable to that with vitamin E analogues, Trolox, or PMHC. An electron-transfer mechanism accounts for the effect of the medium on the antioxidant properties of BR.

  17. Nitrosamine exposure exacerbates high fat diet-mediated type 2 diabetes mellitus, non-alcoholic steatohepatitis, and neurodegeneration with cognitive impairment

    Directory of Open Access Journals (Sweden)

    de la Monte Suzanne M

    2009-12-01

    Full Text Available Abstract Background The current epidemics of type 2 diabetes mellitus (T2DM, non-alcoholic steatohepatitis (NASH, and Alzheimer's disease (AD all represent insulin-resistance diseases. Previous studies linked insulin resistance diseases to high fat diets or exposure to streptozotocin, a nitrosamine-related compound that causes T2DM, NASH, and AD-type neurodegeneration. We hypothesize that low-level exposure to nitrosamines that are widely present in processed foods, amplifies the deleterious effects of high fat intake in promoting T2DM, NASH, and neurodegeneration. Methods Long Evans rat pups were treated with N-nitrosodiethylamine (NDEA by i.p. Injection, and upon weaning, they were fed with high fat (60%; HFD or low fat (5%; LFD chow for 6 weeks. Rats were evaluated for cognitive impairment, insulin resistance, and neurodegeneration using behavioral, biochemical, molecular, and histological methods. Results NDEA and HFD ± NDEA caused T2DM, NASH, deficits in spatial learning, and neurodegeneration with hepatic and brain insulin and/or IGF resistance, and reductions in tau and choline acetyltransferase levels in the temporal lobe. In addition, pro-ceramide genes, which promote insulin resistance, were increased in livers and brains of rats exposed to NDEA, HFD, or both. In nearly all assays, the adverse effects of HFD+NDEA were worse than either treatment alone. Conclusions Environmental and food contaminant exposures to low, sub-mutagenic levels of nitrosamines, together with chronic HFD feeding, function synergistically to promote major insulin resistance diseases including T2DM, NASH, and AD-type neurodegeneration. Steps to minimize human exposure to nitrosamines and consumption of high-fat content foods are needed to quell these costly and devastating epidemics.

  18. Impairment of object recognition memory by maternal bisphenol A exposure is associated with inhibition of Akt and ERK/CREB/BDNF pathway in the male offspring hippocampus.

    Science.gov (United States)

    Wang, Chong; Li, Zhihui; Han, Haijun; Luo, Guangying; Zhou, Bingrui; Wang, Shaolin; Wang, Jundong

    2016-02-03

    Bisphenol A (BPA) is a commonly used endocrine-disrupting chemical used as a component of polycarbonates plastics that has potential adverse effects on human health. Exposure to BPA during development has been implicated in memory deficits, but the mechanism of action underlying the effect is not fully understood. In this study, we investigated the effect of maternal exposure to BPA on object recognition memory and the expressions of proteins important for memory, especially focusing on the ERK/CREB/BDNF pathway. Pregnant Sprague-Dawley female rats were orally treated with either vehicle or BPA (0.05, 0.5, 5 or 50 mg/kg BW/day) during days 9-20 of gestation. Male offspring were tested on postnatal day 21 with the object recognition task. Recognition memory was assessed using the object recognition index (index=the time spent exploring the novel object/(the time spent exploring the novel object+the time spent exploring the familiar object)). In the test session performed 90 min after the training session, BPA-exposed male offspring not only spent more time in exploring the familiar object at the highest dose than the control, but also displayed a significantly decreased the object recognition index at the doses of 0.5, 5 and 50 mg/kg BW/day. During the test session performed 24h after the training session, BPA-treated males did not change the time spent exploring the familiar object, but had a decreased object recognition index at 5 and 50 mg/kg BW/day, when compared to control group. These findings indicate that object recognition memory was susceptible to maternal BPA exposure. Western blot analysis of hippocampi from BPA-treated male offspring revealed a decrease in Akt, phospho-Akt, p44/42 MAPK and phospho-p44/42 MAPK protein levels, compared to controls. In addition, BPA significantly inhibited the levels of phosphorylation of CREB and BDNF in the hippocampus. Our results show that maternal BPA exposure may full impair object recognition memory, and that

  19. Biochemical measurement of bilirubin with an evanescent wave optical sensor

    Science.gov (United States)

    Poscio, Patrick; Depeursinge, Christian D.; Emery, Y.; Parriaux, Olivier M.; Voirin, Guy

    1991-09-01

    Optical sensing techniques can be considered as powerful information sources on the biochemistry of tissue, blood, and physiological fluids. Various sensing modalities can be considered: spectroscopic determination of the fluorescence or optical absorption of the biological medium itself, or more generally, of a reagent in contact with the biological medium. The principle and realization of the optical sensor developed are based on the use of polished fibers: the cladding of a monomode fiber is removed on a longitudinal section. The device can then be inserted into an hypodermic needle for in-vivo measurements. Using this minute probe, local measurements of the tissue biochemistry or metabolic processes can be obtained. The sensing mechanism is based on the propagation of the evanescent wave in the tissues or reagent: the proximity of the fiber core allows the penetration of the model field tail into the sensed medium, with a uniquely defined field distribution. Single or multi-wavelength analysis of the light collected into the fiber yields the biochemical information. Here an example of this sensing technology is discussed. In-vitro measurement of bilirubin in gastric juice demonstrates that the evanescent wave optical sensor provides a sensitivity which matches the physiological concentrations. A device is proposed for in-vivo monitoring of bilirubin concentration in the gastro-oesophageal tract.

  20. Bilirubin inhibits iNOS expression and NO production in response to endotoxin in rats.

    Science.gov (United States)

    Wang, Weizheng W; Smith, Darcey L H; Zucker, Stephen D

    2004-08-01

    The inducible isoform of heme oxygenase (HO), HO-1, has been shown to play an important role in attenuating tissue injury. Because HO-1 catalyzes the rate-limiting step in bilirubin synthesis, we examined the hypothesis that bilirubin is a key mediator of HO-1 cytoprotection, employing a rat model of endotoxemia. Bilirubin treatment resulted in improved survival and attenuated liver injury in response to lipopolysaccharide infusion. Serum levels of NO and tumor necrosis factor alpha, key mediators of endotoxemia, and hepatic inducible nitric oxide synthase (iNOS) expression were significantly lower in bilirubin-treated rodents versus control animals. Both intraperitoneal and local administration of bilirubin also was found to ameliorate hindpaw inflammation induced by the injection of lambda-carrageenan. Consistent with in vivo results, bilirubin significantly inhibited iNOS expression and suppressed NO production in lipopolysaccharide (LPS)-stimulated RAW 264.7 murine macrophages. In contrast, bilirubin treatment induced a threefold increase in LPS-mediated prostaglandin synthesis in the absence of significant changes in cyclooxygenase expression or activity, suggesting that bilirubin enhances substrate availability for eicosanoid synthesis. Bilirubin had no effect on LPS-mediated activation of nuclear factor kappaB or p38 mitogen-activated protein kinase, consistent with a nuclear factor kappaB-independent mechanism of action. Taken together, these data support a cytoprotective role for bilirubin that is mediated, at least in part, through the inhibition of iNOS expression and, potentially, through stimulation of local prostaglandin E2 production. In conclusion, our findings suggest a role for bilirubin in mollifying tissue injury in response to inflammatory stimuli and support the possibility that the phenomenon of "jaundice of sepsis" represents an adaptive physiological response to endotoxemia. Supplementary material for this article can be found on the

  1. Environmental enrichment improves age-related immune system impairment: long-term exposure since adulthood increases life span in mice.

    Science.gov (United States)

    Arranz, Lorena; De Castro, Nuria M; Baeza, Isabel; Maté, Ianire; Viveros, Maria Paz; De la Fuente, Mónica

    2010-08-01

    Age-related changes in immunity have been shown to highly influence morbidity and mortality. The aim of the present work was to study the effects of environmental enrichment (EE) (8-16 weeks) on several functions and oxidative stress parameters of peritoneal leukocytes, previously described as health and longevity markers, in mice at different ages, namely adult (44 +/- 4 weeks), old (69 +/- 4 weeks), and very old (92 +/- 4 weeks). Mortality rates were monitored in control and enriched animals, and effects on survival of long-term exposure to EE until natural death were determined. The results showed that exposure to EE was efficient in improving the function (i.e., macrophage chemotaxis and phagocytosis, lymphocyte chemotaxis and proliferation, natural killer cell activity, interleukin-2 and tumor necrosis factor-alpha levels) and decreasing the oxidative-inflammatory stress (i.e., lowered oxidized glutathione content, xanthine oxidase activity, expression of Toll-like receptors 2 and 4 on CD4 and CD8 cells, and increased reduced glutathione and glutathione peroxidase and catalase activities) of immune cells. These positive effects of EE were especially remarkable in animals at older ages. Importantly, long-term exposure to EE from adult age and until natural death stands out as a useful strategy to extend longevity. Thus, the present work confirms the importance of maintaining active mental and/or physical activity aiming to improve quality of life in terms of immunity, and demonstrates that this active life must be initiated at early stages of the aging process and preserved until death to improve life span.

  2. In vivo manganese exposure modulates Erk, Akt and Darpp-32 in the striatum of developing rats, and impairs their motor function.

    Directory of Open Access Journals (Sweden)

    Fabiano M Cordova

    Full Text Available Manganese (Mn is an essential metal for development and metabolism. However, exposures to high Mn levels may be toxic, especially to the central nervous system (CNS. Neurotoxicity is commonly due to occupational or environmental exposures leading to Mn accumulation in the basal ganglia and a Parkinsonian-like disorder. Younger individuals are more susceptible to Mn toxicity. Moreover, early exposure may represent a risk factor for the development of neurodegenerative diseases later in life. The present study was undertaken to investigate the developmental neurotoxicity in an in vivo model of immature rats exposed to Mn (5, 10 and 20 mg/kg; i.p. from postnatal day 8 (PN8 to PN12. Neurochemical analysis was carried out on PN14. We focused on striatal alterations in intracellular signaling pathways, oxidative stress and cell death. Moreover, motor alterations as a result of early Mn exposure (PN8-12 were evaluated later in life at 3-, 4- and 5-weeks-of-age. Mn altered in a dose-dependent manner the activity of key cell signaling elements. Specifically, Mn increased the phosphorylation of DARPP-32-Thr-34, ERK1/2 and AKT. Additionally, Mn increased reactive oxygen species (ROS production and caspase activity, and altered mitochondrial respiratory chain complexes I and II activities. Mn (10 and 20 mg/kg also impaired motor coordination in the 3(rd, 4(th and 5(th week of life. Trolox™, an antioxidant, reversed several of the Mn altered parameters, including the increased ROS production and ERK1/2 phosphorylation. However, Trolox™ failed to reverse the Mn (20 mg/kg-induced increase in AKT phosphorylation and motor deficits. Additionally, Mn (20 mg/kg decreased the distance, speed and grooming frequency in an open field test; Trolox™ blocked only the decrease of grooming frequency. Taken together, these results establish that short-term exposure to Mn during a specific developmental window (PN8-12 induces metabolic and neurochemical alterations in

  3. 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

    ). 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.......5 in the second, none in the third, and 0.8 in the fourth and following steps. The visible absorption spectrum of bound bilirubin changes in the second, third, and fourth steps. The bilirubin spectra of the different bilirubin-albumin complexes occurring in the transition show a common isosbestic point at 445 nm...

  4. Exposure to an agricultural contaminant, 17β-trenbolone, impairs female mate choice in a freshwater fish.

    Science.gov (United States)

    Tomkins, Patrick; Saaristo, Minna; Allinson, Mayumi; Wong, Bob B M

    2016-01-01

    Despite the pivotal role sexual selection plays in population dynamics and broader evolutionary processes, the impact of chemical pollution on female mate choice is poorly understood. One group of chemical contaminants with the potential to disrupt the mechanisms of female mate choice is endocrine disrupting chemicals (EDCs); a broad class of environmental pollutants that can interfere with the endocrinology of organisms at extremely low concentrations. Recent research has revealed that estrogenic EDCs can affect female mate choice in fish, but the impact of androgenic EDC exposure is yet to be studied. To address this, we investigated the effects of an environmentally relevant concentration of trenbolone - an androgenic steroid used as a growth promoter in the cattle industry - on female mate choice in wild-caught guppies (Poecilia reticulata). We exposed male and female guppies to 17β-trenbolone for 21 days (measured concentration 4ng/L) via a flow-through system, and found that trenbolone-exposed female guppies spent less time associating with males, and were less choosy, compared to unexposed females. In contrast, trenbolone had no impact on male reproductive behavior or morphology. This is the first study to show that androgenic EDC exposure can disrupt female mate choice, highlighting the need for studies to investigate the behavioral impacts of environmental contaminants on both sexes.

  5. Low-level environmental lead exposure and intellectual impairment in children--the current concepts of risk assessment.

    Science.gov (United States)

    Jakubowski, Marek

    2011-03-01

    Lead is an environmental contaminant. The majority of epidemiological research on the health effects of lead has been focused on children, because they are more vulnerable to lead than adults. In children, an elevated blood lead (B-Pb) is associated with reduced Intelligence Quotient (IQ) score. This paper summarizes the current opinions on the assessment of the health risk connected with the children's environmental exposure to lead. The B-Pb level of concern of 100 μg/l proposed by the US Centers of Disease Control in 1991 was for a long time accepted as the guideline value. In the meantime there has been a significant worldwide decrease of B-Pb levels in children and present geometric mean values in the European countries range from 20 to 30 μg/l. The recent analyses of the association of intelligence test scores and B-Pb levels have revealed that the steepest declines in IQ occur at blood levels Food Safety Authority (EFSA) concluded in 2010, on the basis of results of Benchmark Dose (BMD) analysis, that an increase in B-Pb of 12 μg/l (BMDL₀₁) could decrease the IQ score by one point. It seems that this value can be used as a "unit risk" to calculate the possible decrease of IQ and, consequently, influence of the low-level exposure to lead (< 100 μg/l) on the health and socioeconomic status of the exposed population.

  6. Exposure to environmentally persistent free radicals during gestation lowers energy expenditure and impairs skeletal muscle mitochondrial function in adult mice.

    Science.gov (United States)

    Stephenson, Erin J; Ragauskas, Alyse; Jaligama, Sridhar; Redd, JeAnna R; Parvathareddy, Jyothi; Peloquin, Matthew J; Saravia, Jordy; Han, Joan C; Cormier, Stephania A; Bridges, Dave

    2016-06-01

    We have investigated the effects of in utero exposure to environmentally persistent free radicals (EPFRs) on growth, metabolism, energy utilization, and skeletal muscle mitochondria in a mouse model of diet-induced obesity. Pregnant mice were treated with laboratory-generated, combustion-derived particular matter (MCP230). The adult offspring were placed on a high-fat diet for 12 wk, after which we observed a 9.8% increase in their body weight. The increase in body size observed in the MCP230-exposed mice was not associated with increases in food intake but was associated with a reduction in physical activity and lower energy expenditure. The reduced energy expenditure in mice indirectly exposed to MCP230 was associated with reductions in skeletal muscle mitochondrial DNA copy number, lower mRNA levels of electron transport genes, and reduced citrate synthase activity. Upregulation of key genes involved in ameliorating oxidative stress was also observed in the muscle of MCP230-exposed mice. These findings suggest that gestational exposure to MCP230 leads to a reduction in energy expenditure at least in part through alterations to mitochondrial metabolism in the skeletal muscle.

  7. Low-dose thioperamide injected into the cerebellar vermis of mice immediately after exposure to the elevated plus-maze impairs their avoidance behavior on re-exposure to the apparatus

    Directory of Open Access Journals (Sweden)

    J. Costa Neto

    2013-11-01

    Full Text Available The present study investigated the effect of thioperamide (THIO, an H3 histaminergic receptor antagonist, microinjected into the cerebellar vermis on emotional memory consolidation in male Swiss albino mice re-exposed to the elevated plus-maze (EPM. We implanted a guide cannula into the cerebellar vermis using stereotactic surgery. On the third day after surgery, we performed behavioral tests for two consecutive days. On the first day (exposure, the mice (n=10/group were exposed to the EPM and received THIO (0.06, 0.3, or 1.5 ng/0.1 µL immediately after the end of the session. Twenty-four hours later, the mice were re-exposed to the EPM under the same experimental conditions, but without drug injection. A reduction in the exploration of the open arms upon re-exposure to the EPM (percentage of number of entries and time spent in open arms compared with the initial exposure was used as an indicator of learning and memory. One-way analysis of variance (ANOVA followed by the Duncan post hoc test was used to analyze the data. Upon re-exposure, exploratory activity in the open arms was reduced in the control group, and with the two highest THIO doses: 0.3 and 1.5 ng/0.1 µL. No reduction was seen with the lowest THIO dose (0.06 ng/0.1 µL, indicating inhibition of the consolidation of emotional memory. None of the doses interfered with the animals' locomotor activity. We conclude that THIO at the lowest dose (0.06 ng/0.1 µL microinjected into the cerebellum impaired emotional memory consolidation in mice.

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

    Science.gov (United States)

    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…

  9. 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.

    2015-01-01

    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 ri

  10. New Sorbent for Bilirubin Removal from Human Plasma: Albumin Immobilized Microporous Membranous PTFE Capillaries

    Institute of Scientific and Technical Information of China (English)

    Lei ZHANG; Gu JIN

    2005-01-01

    In this study, we developed a tailored capillary sorbent for bilirubin removal. For immobilized bioligand, capillaries were grafted with epoxy groups using RIGP. The HSA immobilized capillaries has a high affinity adsorption capacity (71.2 mg bilirubin/g polymer) and a shorter adsorption equilibrium time (about 60 min).

  11. Association of bilirubin and protein thiols in relation to copper and ceruloplasmin in hyperbilirubinemic patients

    Institute of Scientific and Technical Information of China (English)

    Mungli Prakash; Jeevan K Shetty; Roshan D'Souza; Suhasa Upadhya; Vijay Kumar

    2009-01-01

    Objective:Bilirubin is a double edged sword in biological system,acting as a toxic molecule and cytoprotecrant.Unconjugated bilirubin is proved to show antioxidant activity in vitro and in vivo.In the current work we tried to know the relationship between both conjugated and unconjugated bilirubin with copper and protein thiols in patients with hyperbilirnbinemia.Methods:Study was conducted on 56 hyperbilirubinemic cases and 56 healthy controls.Serum copper,ceruloplasmin,protein thiols,total bilirubin,conjugated and unconjugated bilirubin,unconjugated bilimbin/albumin ratio,total protein,albumin,AST,ALT and ALP were estimated.Results:There was significant increase in serum copper,total bilirubin,conjugated and unconjugated bilimbin.uriconjugated bilirubin/albumin ratio,AST,ALT,and ALP,and decrease in serum ceruloplasmin,protein thiols,total protein,and albumin in hyperbilimbinemic cases when compared to healthy controls.Conjugated bilimbin correlated positively with liver enzymes AST and ALP,and negatively with protein thials,total protein and albumin.Unconjugated bilirubin correlated positively with ALT.Protein thiols correlated negatively with copper and positively with ceruloplasmin,and also correlated negativelv with liver enzymes like AST,ALT and ALP,and positively with total protein and albumin.Conclusion:Combination of elevated levels of trace elements like copper and availability of reducing agent like bilimbin may prove deleterious by generating free radicals.

  12. EXPERIMENTAL AND CLINICAL STUDY ON BILIRUBIN NEUROTOXICITY DETECTED BY VISUAL EVOKED POTENTIALS TO FLASH

    Institute of Scientific and Technical Information of China (English)

    贲晓明; 秦玉明; 吴圣楣; 张惠民; 陈舜年; 夏振炜

    2001-01-01

    Objective Evaluate the sensitivity and reliability of visual evoked potential to flash ( FVEP ) in detecting bilirubin neurotoxicity and approach the risk parameters of bilirubin neurotoxicity in hyperbilirubinernia newborns. Methods Based on the successful establishment of animal models for acute bilirubin encephalopathy by intraperitoneal infusion of bilirubin with a dosage of 100~200μg /g body weight to 1-weekold guinea pigs, the F-VEP was recorded in animal models and human neonates with hyperbilirubinemia, and the sensitivity and reliability of F-VEP in detecting bilirubin neurotoxicity were evaluated. Results F-VEP features and its P1 latency significantly correlated to brain adenosine triphosphate (ATP) level, neurobehavioral and neuropathological changes in experimental bilirubin encephalopathy ; neonates with hyperbilirubinemia showed significant F-VEP changes characterized by absence of P1 or P1 latency prolonged in 1~7-dayold newborns, especially when the jaundice was caused by immunoincompatibility and infectious diseases. Conclusion F-VEP would be a good discriminator for bilirubin neurotoxicity, and can become a promising technique in monitoring bilirubin encephalopathy.

  13. Effect of bilirubin on triglyceride synthesis in streptozotocin-induced diabetic nephropathy.

    Science.gov (United States)

    Xu, Jianwei; Lee, Eun Seong; Baek, Seon Ha; Ahn, Shin-Young; Kim, Sejoong; Na, Ki Young; Chae, Dong-Wan; Chin, Ho Jun

    2014-09-01

    We aimed to elucidate the effect of bilirubin on dyslipidemia and nephropathy in a diabetes mellitus (DM) type I animal model. Sprague-Dawley rats were separated into control, DM, and bilirubin-treated DM (Bil) groups. The Bil group was injected intraperitoneally with 60 mg/kg bilirubin 3 times per week and hepatoma cells were cultured with bilirubin at a concentration of 0.3 mg/dL. The Bil group showed lower serum creatinine levels 5 weeks after diabetes onset. Bilirubin treatment also decreased the amount of mesangial matrix, lowered the expression of renal collagen IV and transforming growth factor (TGF)-β1, and reduced the level of apoptosis in the kidney, compared to the DM group. These changes were accompanied by decreased tissue levels of hydrogen superoxide and NADPH oxidase subunit proteins. Bilirubin decreased serum total cholesterol, high-density lipoprotein cholesterol (HDL-C), free fatty acids, and triglycerides (TGs), as well as the TG content in the liver tissues. Bilirubin suppressed protein expression of LXRα, SREBP-1, SCD-1, and FAS, factors involved in TG synthesis that were elevated in the livers of DM rats and hepatoma cells under high-glucose conditions. In conclusion, bilirubin attenuates renal dysfunction and dyslipidemia in diabetes by suppressing LXRα and SREBP-1 expression and oxidative stress.

  14. 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...

  15. 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 m...

  16. 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 biliverdi

  17. The Contribution of Childhood Parental Rejection and Early Androgen Exposure to Impairments in Socio-Cognitive Skills in Intimate Partner Violence Perpetrators with High Alcohol Consumption

    Directory of Open Access Journals (Sweden)

    Luis Moya-Albiol

    2013-08-01

    Full Text Available Alcohol consumption, a larger history of childhood parental rejection, and high prenatal androgen exposure have been linked with facilitation and high risk of recidivism in intimate partner violence (IPV perpetrators. Participants were distributed into two groups according to their alcohol consumption scores as high (HA and low (LA. HA presented a higher history of childhood parental rejection, prenatal masculinization (smaller 2D:4D ratio, and violence-related scores than LA IPV perpetrators. Nonetheless, the former showed poor socio-cognitive skills performance (cognitive flexibility, emotional recognition and cognitive empathy. Particularly in HA IPV perpetrators, the history of childhood parental rejection was associated with high hostile sexism and low cognitive empathy. Moreover, a masculinized 2D:4D ratio was associated with high anger expression and low cognitive empathy. Parental rejection during childhood and early androgen exposure are relevant factors for the development of violence and the lack of adequate empathy in adulthood. Furthermore, alcohol abuse plays a key role in the development of socio-cognitive impairments and in the proneness to violence and its recidivism. These findings contribute to new coadjutant violence intervention programs, focused on the rehabilitation of basic executive functions and emotional decoding processes and on the treatment of alcohol dependence.

  18. PM2.5, SO2 and NO2 co-exposure impairs neurobehavior and induces mitochondrial injuries in the mouse brain.

    Science.gov (United States)

    Ku, Tingting; Ji, Xiaotong; Zhang, Yingying; Li, Guangke; Sang, Nan

    2016-11-01

    Air pollution is a serious environmental health problem that has been previously associated with neuropathological disorders. However, current experimental evidence mainly focuses on the adverse effects of a single air pollutant, ignoring the biological responses to the co-existence of these pollutants. In the present study, we co-exposed C57BL/6 J mice to PM2.5, SO2 and NO2 and explored their neurobehavior, histopathologic abnormalities, apoptosis-related protein expression and mitochondrial dysfunction. The results indicate that co-exposure to PM2.5, SO2 and NO2 impaired spatial learning and memory and caused abnormal expression of apoptosis-related genes (p53, bax and bcl-2). Additionally, these alterations were related to morphological changes in mitochondria, a reduction of ATP, the elevation of mitochondrial fission proteins and the downregulation of fusion proteins. These findings provide a basis for the understanding of mitochondrial abnormality-related neuropathological dysfunction in response to co-exposure to ambient air pollutants, which suggests an adaptive response to the frangibility of the central nerve system.

  19. Repeated Acute Oral Exposure to Cannabis sativa Impaired Neurocognitive Behaviours and Cortico-hippocampal Architectonics in Wistar Rats.

    Science.gov (United States)

    Imam, A; Ajao, M S; Akinola, O B; Ajibola, M I; Ibrahim, A; Amin, A; Abdulmajeed, W I; Lawal, Z A; Ali-Oluwafuyi, A

    2017-03-06

    The most abused illicit drug in both the developing and the developed world is Cannabis disposing users to varying forms of personality disorders. However, the effects of cannabis on cortico-hippocampal architecture and cognitive behaviours still remain elusive.  The present study investigated the neuro-cognitive implications of oral cannabis use in rats. Eighteen adult Wistar rats were randomly grouped to three. Saline was administered to the control rats, cannabis (20 mg/kg) to the experimental group I, while Scopolamine (1 mg/kg. ip) was administered to the last group as a standard measure for the cannabis induced cognitive impairment. All treatments lasted for seven consecutive days. Open Field Test (OFT) was used to assess locomotor activities, Elevated Plus Maze (EPM) for anxiety-like behaviour, and Y maze paradigm for spatial memory and data subjected to ANOVA and T test respectively. Thereafter, rats were sacrificed and brains removed for histopathological studies. Cannabis significantly reduced rearing frequencies in the OFT and EPM, and increased freezing period in the OFT. It also reduced percentage alternation similar to scopolamine in the Y maze, and these effects were coupled with alterations in the cortico-hippocampal neuronal architectures. These results point to the detrimental impacts of cannabis on cortico-hippocampal neuronal architecture and morphology, and consequently cognitive deficits.

  20. Exposure of BALB/c mice to diesel engine exhaust origin secondary organic aer-osol (DE-SOA) during the developmental stages impairs the social behavior in adult life of the males

    OpenAIRE

    2016-01-01

    Secondary organic aerosol (SOA) is a component of particulate matter (PM) 2.5 and formed in the atmosphere by oxidation of volatile organic compounds. Recently, we have reported that inhalation exposure to diesel engine exhaust (DE) originated SOA (DE-SOA) affect novel object recognition ability and impair maternal behavior in adult mice. However, it is not clear whether early life exposure to SOA during the de-velopmental stages affect social behavior in adult life or not. In the present stu...

  1. 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

  2. Antioxidant activity of inulin and its role in the prevention of human colonic muscle cell impairment induced by lipopolysaccharide mucosal exposure.

    Directory of Open Access Journals (Sweden)

    Valentina Pasqualetti

    Full Text Available BACKGROUND: Fructans, such as inulin, are dietary fibers which stimulate gastro-intestinal (GI function acting as prebiotics. Lipopolysaccharide (LPS impairs GI motility, through production of reactive oxygen species. The antioxidant activity of various fructans was tested and the protective effect of inulin on colonic smooth muscle cell (SMC impairment, induced by exposure of human mucosa to LPS, was assessed in an ex vivo experimental model. METHODS: The antioxidant capacity of fructans was measured in an in vitro system that simulates cooking and digestion processes. Human colonic mucosa and submucosa, obtained from disease-free margins of resected segments for cancer, were sealed between two chambers, with the mucosal side facing upwards with Krebs solution with or without purified LPS from a pathogenic strain of Escherichia coli (O111:B4 and inulin (Frutafit IQ, and the submucosal side facing downwards into Krebs solution. The solutions on the submucosal side were collected following mucosal exposure to Krebs in the absence (N-undernatant or presence of LPS (LPS-undernatant or LPS+inulin (LPS+INU-undernatant. Undernatants were tested for their antioxidant activity and the effects on SMCs contractility. Inulin protective effects on mucosa and submucosa layers were assessed measuring the protein oxidation level in the experimental conditions analyzed. RESULTS: Antioxidant activity of inulin, which was significantly higher compared to simple sugars, remained unaltered despite cooking and digestion processes. Inulin protected the mucosal and submucosal layers against protein oxidation. Following exposure to LPS-undernatant, a significant decrease in maximal acetylcholine (Ach-induced contraction was observed when compared to the contraction induced in cells incubated with the N-undernatant (4±1% vs 25±5% respectively, P<0.005 and this effect was completely prevented by pre-incubation of LPS with Inulin (35±5%. CONCLUSIONS: Inulin protects

  3. Neonatal Exposure to Endocrine Disrupting Chemicals Impair Learning Behaviour by Disrupting Hippocampal Organization in Male Swiss Albino Mice.

    Science.gov (United States)

    Bhaskar, Rakesh; Mishra, Ashish K; Mohanty, Banalata

    2017-02-16

    Hippocampus is highly susceptible to endocrine disrupting chemicals exposure particularly during the critical phase of brain development. In the present study, mice offspring were exposed to endocrine disruptors mancozeb (MCZ) and imidacloprid (IMI) individually (40 mg MCZ and 0.65 mg IMI/kg/day) as well as to their equimixture (40 mg MCZ + 0.65 mg IMI/kg/day) through the diet of lactating mothers from post-natal day (PND) 1 to PND 28. Half of the randomly selected male offspring were killed at PND 29 and the rest half were left unexposed and killed at PND 63. Brain weight, histology, plasma hormone profile and working memory performance were the various endpoints studied. Brain weight was significantly decreased in the mixture-exposed group at PND 29, which persisted to PND 63. Total thickness of pyramidal cell layers decreased significantly along with misalignment, shrinkage and degeneration of pyramidal neurons in CA1 and CA3 regions of the IMI and mixture-exposed groups. The length and branch points of dendrites of pyramidal neurons were decreased significantly in mixture-exposed group at both PND 29 and PND 63. Dendritic spine density was also reduced in mixture-exposed group offspring. Testosterone level was significantly decreased only at PND 29 but corticosterone level was increased at both PND 29 and PND 6 in mixture-exposed offspring. T-maze task performance revealed significantly increased time duration and reduced path efficiency in mixture-exposed group offspring. The results thus indicate that pesticide mixture exposure could lead to changes in learning behaviour even at doses that individually did not induce any adverse effect on hippocampal organization. This article is protected by copyright. All rights reserved.

  4. 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

    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......: During the period, 73 patients where operated with a portoenterostomy ad modum Kasai. Patients older than 84 days at the time of operation were excluded, 54 patients were available for analysis. Conjugated bilirubin in μmol/l and the percentage value were significantly above the DHMA threshold limit......: mean 129.7 μmol/l (42-334 μmol/l) and 73% (28-97%), respectively. CONCLUSION: The total amount of conjugated bilirubin above 20 μmol/l is sufficient to require further evaluation for biliary atresia. The percentage value is unnecessary and may cause confusion. FUNDING: none. TRIAL REGISTRATION...

  5. Exposure to 900 MHz electromagnetic fields activates the mkp-1/ERK pathway and causes blood-brain barrier damage and cognitive impairment in rats.

    Science.gov (United States)

    Tang, Jun; Zhang, Yuan; Yang, Liming; Chen, Qianwei; Tan, Liang; Zuo, Shilun; Feng, Hua; Chen, Zhi; Zhu, Gang

    2015-03-19

    With the rapid increase in the number of mobile phone users, the potential adverse effects of the electromagnetic field radiation emitted by a mobile phone has become a serious concern. This study demonstrated, for the first time, the blood-brain barrier and cognitive changes in rats exposed to 900 MHz electromagnetic field (EMF) and aims to elucidate the potential molecular pathway underlying these changes. A total of 108 male Sprague-Dawley rats were exposed to a 900 MHz, 1 mW/cm(2) EMF or sham (unexposed) for 14 or 28 days (3h per day). The specific energy absorption rate (SAR) varied between 0.016 (whole body) and 2 W/kg (locally in the head). In addition, the Morris water maze test was used to examine spatial memory performance determination. Morphological changes were investigated by examining ultrastructural changes in the hippocampus and cortex, and the Evans Blue assay was used to assess blood brain barrier (BBB) damage. Immunostaining was performed to identify heme oxygenase-1 (HO-1)-positive neurons and albumin extravasation detection. Western blot was used to determine HO-1 expression, phosphorylated ERK expression and the upstream mediator, mkp-1 expression. We found that the frequency of crossing platforms and the percentage of time spent in the target quadrant were lower in rats exposed to EMF for 28 days than in rats exposed to EMF for 14 days and unexposed rats. Moreover, 28 days of EMF exposure induced cellular edema and neuronal cell organelle degeneration in the rat. In addition, damaged BBB permeability, which resulted in albumin and HO-1 extravasation were observed in the hippocampus and cortex. Thus, for the first time, we found that EMF exposure for 28 days induced the expression of mkp-1, resulting in ERK dephosphorylation. Taken together, these results demonstrated that exposure to 900 MHz EMF radiation for 28 days can significantly impair spatial memory and damage BBB permeability in rat by activating the mkp-1/ERK pathway.

  6. Selective TNF-α targeting with infliximab attenuates impaired oxygen metabolism and contractile function induced by an acute exposure to air particulate matter.

    Science.gov (United States)

    Marchini, Timoteo; D'Annunzio, Verónica; Paz, Mariela L; Cáceres, Lourdes; Garcés, Mariana; Perez, Virginia; Tasat, Deborah; Vanasco, Virginia; Magnani, Natalia; Gonzalez Maglio, Daniel; Gelpi, Ricardo J; Alvarez, Silvia; Evelson, Pablo

    2015-11-15

    Inflammation plays a central role in the onset and progression of cardiovascular diseases associated with the exposure to air pollution particulate matter (PM). The aim of this work was to analyze the cardioprotective effect of selective TNF-α targeting with a blocking anti-TNF-α antibody (infliximab) in an in vivo mice model of acute exposure to residual oil fly ash (ROFA). Female Swiss mice received an intraperitoneal injection of infliximab (10 mg/kg body wt) or saline solution, and were intranasally instilled with a ROFA suspension (1 mg/kg body wt). Control animals were instilled with saline solution and handled in parallel. After 3 h, heart O2 consumption was assessed by high-resolution respirometry in left ventricle tissue cubes and isolated mitochondria, and ventricular contractile reserve and lusitropic reserve were evaluated according to the Langendorff technique. ROFA instillation induced a significant decrease in tissue O2 consumption and active mitochondrial respiration by 32 and 31%, respectively, compared with the control group. While ventricular contractile state and isovolumic relaxation were not altered in ROFA-exposed mice, impaired contractile reserve and lusitropic reserve were observed in this group. Infliximab pretreatment significantly attenuated the decrease in heart O2 consumption and prevented the decrease in ventricular contractile and lusitropic reserve in ROFA-exposed mice. Moreover, infliximab-pretreated ROFA-exposed mice showed conserved left ventricular developed pressure and cardiac O2 consumption in response to a β-adrenergic stimulus with isoproterenol. These results provides direct evidence linking systemic inflammation and altered cardiac function following an acute exposure to PM and contribute to the understanding of PM-associated cardiovascular morbidity and mortality.

  7. Influences of Chronic Mild Stress Exposure on Motor, Non-Motor Impairments and Neurochemical Variables in Specific Brain Areas of MPTP/Probenecid Induced Neurotoxicity in Mice.

    Directory of Open Access Journals (Sweden)

    Udaiyappan Janakiraman

    Full Text Available Parkinson's disease (PD is regarded as a movement disorder mainly affecting the elderly population and occurs due to progressive loss of dopaminergic (DAergic neurons in nigrostriatal pathway. Patients suffer from non-motor symptoms (NMS such as depression, anxiety, fatigue and sleep disorders, which are not well focussed in PD research. Depression in PD is a predominant /complex symptom and its pathology lies exterior to the nigrostriatal system. The main aim of this study is to explore the causative or progressive effect of chronic mild stress (CMS, a paradigm developed as an animal model of depression in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (25 mg/kg. body wt. with probenecid (250 mg/kg, s.c. (MPTP/p induced mice model of PD. After ten i.p. injections (once in 3.5 days for 5 weeks of MPTP/p or exposure to CMS for 4 weeks, the behavioural (motor and non-motor impairments, levels and expressions of dopamine (DA, serotonin (5-HT, DAergic markers such as tyrosine hydroxylase (TH, dopamine transporter (DAT, vesicular monoamine transporters-2 (VMAT 2 and α-synuclein in nigrostriatal (striatum (ST and substantia nigra (SN and extra-nigrostriatal (hippocampus, cortex and cerebellum tissues were analysed. Significantly decreased DA and 5-HT levels, TH, DAT and VMAT 2 expressions and increased motor deficits, anhedonia-like behaviour and α-synuclein expression were found in MPTP/p treated mice. Pre and/or post exposure of CMS to MPTP/p mice further enhanced the MPTP/p induced DA and 5-HT depletion, behaviour abnormalities and protein expressions. Our results could strongly confirm that the exposure of stress after MPTP/p injections worsens the symptoms and neurochemicals status of PD.

  8. 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 sub

  9. Maternal Exposure to Cadmium and Manganese Impairs Reproduction and Progeny Fitness in the Sea Urchin Paracentrotus lividus.

    Directory of Open Access Journals (Sweden)

    Oriana Migliaccio

    Full Text Available Metal contamination represents one of the major sources of pollution in marine environments. In this study we investigated the short-term effects of ecologically relevant cadmium and manganese concentrations (10(-6 and 3.6 x 10(-5 M, respectively on females of the sea urchin Paracentrotus lividus and their progeny, reared in the absence or presence of the metal. Cadmium is a well-known heavy metal, whereas manganese represents a potential emerging contaminant, resulting from an increased production of manganese-containing compounds. The effects of these agents were examined on both P. lividus adults and their offspring following reproductive state, morphology of embryos, nitric oxide (NO production and differential gene expression. Here, we demonstrated that both metals differentially impaired the fertilization processes of the treated female sea urchins, causing modifications in the reproductive state and also affecting NO production in the ovaries. A detailed analysis of the progeny showed a high percentage of abnormal embryos, associated to an increase in the endogenous NO levels and variations in the transcriptional expression of several genes involved in stress response, skeletogenesis, detoxification, multi drug efflux processes and NO production. Moreover, we found significant differences in the progeny from females exposed to metals and reared in metal-containing sea water compared to embryos reared in non-contaminated sea water. Overall, these results greatly expanded previous studies on the toxic effects of metals on P. lividus and provided new insights into the molecular events induced in the progeny of sea urchins exposed to metals.

  10. Primary Biliary Cirrhosis and Hemolytic Anemia Confusing Serum Bilirubin Levels

    Directory of Open Access Journals (Sweden)

    M Brackstone

    2000-01-01

    Full Text Available Hemolysis is observed in more than 50% of patients with cirrhosis. However, there has been little documention of the association of primary biliary cirrhosis with autoimmune hemolytic anemia. Two cases, found within a single practice, of primary biliary cirrhosis coexisting with autoimmune hemolysis and a third case coexisting with hereditary spherocytosis are presented. Anemia in such patients is commonly attributed to chronic disease, and hyperbilirubinemia is attributed to primary biliary cirrhosis. These patients were considered for liver transplantation until the diagnosis of a comorbid hemolytic process was established. This association may be more prevalent than previously recognized. A diagnosis of comorbid hemolysis must always be considered in context with anemia and serum bilirubin levels that rise out of proportion to the severity of the primary biliary cirrhosis.

  11. Maternal low-dose estradiol-17β exposure during pregnancy impairs postnatal progeny weight development and body composition

    Energy Technology Data Exchange (ETDEWEB)

    Werner Fürst, Rainer [Physiology Weihenstephan, Technische Universität München, 85354 Freising-Weihenstephan (Germany); ZIEL PhD Graduate school ‘Epigenetics, Imprinting and Nutrition’, Technische Universität München, 85354 Freising-Weihenstephan (Germany); Pistek, Veronika Leopoldine; Kliem, Heike [Physiology Weihenstephan, Technische Universität München, 85354 Freising-Weihenstephan (Germany); Skurk, Thomas; Hauner, Hans [ZIEL Dep. Nutritional Medicine, Technische Universität München, 85354 Freising-Weihenstephan (Germany); Klinikum rechts der Isar, Technische Universität München, 81675 München (Germany); Meyer, Heinrich Herman Dietrich [Physiology Weihenstephan, Technische Universität München, 85354 Freising-Weihenstephan (Germany); Ulbrich, Susanne Ernestine, E-mail: ulbrich@wzw.tum.de [Physiology Weihenstephan, Technische Universität München, 85354 Freising-Weihenstephan (Germany)

    2012-09-15

    Endocrine disrupting chemicals with estrogenic activity play an important role as obesogens. However, studies investigating the most potent natural estrogen, estradiol-17β (E2), at low dose are lacking. We examined endocrine and physiological parameters in gilts receiving distinct concentrations of E2 during pregnancy. We then investigated whether adverse effects prevail in progeny due to a potential endocrine disruption. E2 was orally applied to gilts during the entire period of pregnancy. The concentrations represented a daily consumption at the recommended ADI level (0.05 μg/kg body weight/day), at the NOEL (10 μg/kg body weight/day) and at a high dosage (1000 μg/kg body weight/day). Plasma hormone concentrations were determined using enzyme immuno assays. Offspring body fat was assessed by dual-energy X-ray absorptiometry scanning. In treated gilts receiving 1000 μg E2/kg body weight/day we found significantly elevated plasma E2 levels during pregnancy, paralleled by an increased weight gain. While offspring showed similar weight at birth, piglets exhibited a significant reduction in weight at weaning even though their mothers had only received 0.05 μg E2/kg body weight/day. At 8 weeks of age, specifically males showed a significant increase in overall body fat percentage. In conclusion, prenatal exposure to low doses of E2 affected pig offspring development in terms of body weight and composition. In line with findings from other obesogens, our data suggest a programming effect during pregnancy for E2 causative for the depicted phenotypes. Therefore, E2 exposure may imply a possible contribution to childhood obesity. -- Highlights: ► We investigate the potential role of estradiol-17β (E2) as an obesogen. ► We orally apply E2 at the ADI, NOEL and a high dose to gilts during pregnancy. ► Offspring weight is similar at birth but reduced at weaning even after ADI treatment. ► Male offspring only exhibit an increase in overall body fat percentage

  12. Peripubertal Caffeine Exposure Impairs Longitudinal Bone Growth in Immature Male Rats in a Dose- and Time-Dependent Manner.

    Science.gov (United States)

    Choi, Yun-Young; Choi, Yuri; Kim, Jisook; Choi, Hyeonhae; Shin, Jiwon; Roh, Jaesook

    2016-01-01

    This study investigated the dose- and time-dependent effects of caffeine consumption throughout puberty in peripubertal rats. A total of 85 male SD rats were randomly divided into four groups: control and caffeine-fed groups with 20, 60, or 120 mg/kg/day through oral gavage for 10, 20, 30, or 40 days. Caffeine decreased body weight gain and food consumption in a dose- and time-dependent manner, accompanied by a reduction in muscle and body fat. In addition, it caused a shortening and lightening of leg bones and spinal column. The total height of the growth plate decreased sharply at 40 days in the controls, but not in the caffeine-fed groups, and the height of hypertrophic zone in the caffeine-fed groups was lower than in the control. Caffeine increased the height of the secondary spongiosa, whereas parameters related to bone formation, such as bone area ratio, thickness and number of trabeculae, and bone perimeter, were significantly reduced. Furthermore, serum levels of IGF-1, estradiol, and testosterone were also reduced by the dose of caffeine exposure. Our results demonstrate that caffeine consumption can dose- and time-dependently inhibit longitudinal bone growth in immature male rats, possibly by blocking the physiologic changes in body composition and hormones relevant to bone growth.

  13. Bilirubin and Progression of Nephropathy in Type 2 Diabetes : A Post Hoc Analysis of RENAAL With Independent Replication in IDNT

    NARCIS (Netherlands)

    Riphagen, Ineke J.; Deetman, Petronella E.; Bakker, Stephan J. L.; Navis, Gerarda; Cooper, Mark E.; Lewis, Julia B.; de Zeeuw, Dick; Lambers Heerspink, Hiddo

    2014-01-01

    Bilirubin, a potent endogenous antioxidant, was found to protect against the development of diabetic nephropathy (DN) in rodents. In humans, cross-sectional studies found an inverse relation between bilirubin and DN. We prospectively investigated whether bilirubin is associated with progression of D

  14. [Haemolysis and turbidity influence on three analysis methods of quantitative determination of total and conjugated bilirubin on ADVIA 1650].

    Science.gov (United States)

    Gobert De Paepe, E; Munteanu, G; Schischmanoff, P O; Porquet, D

    2008-01-01

    Plasma bilirubin testing is crucial to prevent the occurrence of neonatal kernicterus. Haemolysis may occur during sampling and interfere with bilirubin determination. Moreover, lipidic infusions may induce plasma lipemia and also interfere with bilirubin measurement. We evaluated the interference of haemolysis and lipemia with three methods of total and direct bilirubin measurement adaptated on an Advia 1650 analyser (Siemens Medical Solutions Diagnostics) : Synermed (Sofibel), Bilirubin 2 (Siemens) and Bilirubin Auto FS (Diasys). The measurement of total bilirubin was little affected by haemolysis with all three methods. The Bilirubin 2 (Siemens) method was the less sensitive to haemolysis even at low bilirubin levels. The measurement of conjugated bilirubin was significantly altered by low heamoglobin concentrations for Bilirubin Auto FS(R) (30 microM or 0,192 g/100 mL haemoglobin) and for Synermed (60 microM or 0,484 g/100 mL haemoglobin). In marked contrast, we found no haemoglobin interference with the Direct Bilirubin 2 reagent which complied with the method validation criteria from the French Society for Biological Chemistry. The lipemia up to 2 g/L of Ivelip did not affect neither the measurement of total bilirubin for all three methods nor the measurement of conjugated bilirubin with the Diasys and Siemens reagents. However, we observed a strong interference starting at 0,5 g/L of Ivelip with the Synermed reagent. Our data suggest that both Siemens and Diasys methods allow to measure accurately total and conjugated bilirubin in hemolytic and lipemic samples, nevertheless, the Siemens methodology is less affected by these interferences.

  15. Intraperitoneal Bilirubin Administration Decreases Infarct Area in a Rat Coronary Ischemia/Reperfusion Model

    Directory of Open Access Journals (Sweden)

    Ron eBen-Amotz

    2014-02-01

    Full Text Available Bilirubin was previously considered a toxin byproduct of heme catabolism. However, a mounting body of evidence suggests that at physiological doses, bilirubin is a powerful antioxidant and anti-atherosclerotic agent. Recent clinical studies have shown that human beings with genetically-induced hyperbilirubinemia (Gilbert Syndrome are protected against coronary heart disease. The purpose of this study was to investigate whether administration of exogenous bilirubin to normal rats would convey similar protective effects in an experimental model of coronary ischemia. We hypothesized that intraperitoneal bilirubin administration 1 hour before injury would decrease infarct area and preserve left ventricular (LV systolic function when compared to non-treated rats. Coronary ischemia was induced by temporary (30 min ligation of the left anterior descending coronary artery in control or bilirubin treated rats, followed by a 1-hour period of reperfusion. LV function was estimated by measurements of fractional shortening and fractional area shortening using echocardiography. LV function decreased in both experimental groups after ischemia and reperfusion, although in bilirubin-treated rats fractional shortening was less depressed during the period of ischemia (18.8 vs 25.8%, p = 0.034. Infarct size was significantly reduced in the bilirubin treated group compared to the non-treated group (13.34% vs 25.5%, p = 0.0067. Based on the results of this study, bilirubin supplementation appears to provide significant decrease in infarct size although protective effects on LV function were noted only during the period of ischemia. This result also suggests that lipid soluble antioxidant bilirubin prevents the oxidation of cardiolipin and decreases the infarct size in the heart during ischemia.

  16. Relation of Pre-anthracycline Serum Bilirubin Levels to Left Ventricular Ejection Fraction After Chemotherapy.

    Science.gov (United States)

    Vera, Trinity; D'Agostino, Ralph B; Jordan, Jennifer H; Whitlock, Matthew C; Meléndez, Giselle C; Lamar, Zanetta S; Porosnicu, Mercedes; Bonkovsky, Herbert L; Poole, Leslie B; Hundley, W Gregory

    2015-12-01

    Myocardial injury because of oxidative stress manifesting through reductions in left ventricular ejection fraction (LVEF) may occur after the administration of anthracycline-based chemotherapy (A-bC). We hypothesized that bilirubin, an effective endogenous antioxidant, may attenuate the reduction in LVEF that sometimes occurs after receipt of A-bC. We identified 751 consecutively treated patients with cancer who underwent a pre-A-bC LVEF measurement, exhibited a serum total bilirubin level bilirubin and LVEF changes. The LVEF decreased by 10.7 ± 13.7%, 8.9 ± 11.8%, and 7.7 ± 11.5% in group 1 (bilirubin at baseline ≤0.5 mg/dl), group 2 (bilirubin 0.6 to 0.8 mg/dl), and group 3 (bilirubin 0.9 to 1.9 mg/dl), respectively. More group 1 patients experienced >15% decrease in LVEF compared with those in group 3 (p = 0.039). After adjusting for age, coronary artery disease/myocardial infarction, diabetes mellitus, hematocrit, and the use of cardioactive medications, higher precancer treatment bilirubin levels and lesser total anthracycline doses were associated with LVEF preservation (p = 0.047 and 0.011, respectively). In patients treated with anthracyclines who subsequently develop symptoms associated with heart failure, pre-anthracycline treatment serum bilirubin levels inversely correlate with subsequent deterioration in post-cancer treatment LVEF. In conclusion, these results suggest that increased levels of circulating serum total bilirubin, an intrinsic antioxidant, may facilitate preservation of LVEF in patients receiving A-bC for cancer.

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

    DEFF Research Database (Denmark)

    Honoré, B; Sato, H; Brodersen, R

    1988-01-01

    Light absorption and CD spectra of bound bilirubin and albumin fluorescence spectra have been recorded from mixtures containing albumin, A, bilirubin, B, and laurate, L, in Tris-NaCl buffer at pH 8.2, 25 degrees C. Concentrations of the corresponding stoichiometric complexes, ABiLj, for i = 0....... Brodersen et al. (1987) Eur. J. Biochem. 169, 487-495). The results were utilized at the microscopic level to investigate ligand-induced conformational changes. When laurate was bound to AB, a decrease of the distance between Trp-214 and the bound bilirubin occurred, as measured according to Förster...

  18. Enhanced bilirubin binding to different mammalian erythrocytes in the presence of magnesium ions

    OpenAIRE

    M. K. Ali; Siddiqui, M. U.; Tayyab, S.

    2001-01-01

    Effect of magnesium ions on the binding of bilirubin to erythrocytes of different mammalian species, namely, human, buffalo, goat and sheep was studied. Increase in the concentration of magnesium ions led to a gradual increase in the erythrocyte-bound bilirubin in both human and buffalo erythrocytes whereas in sheep and goat erythrocytes, the pronounced increase was found beyond 2.0 and 2.7 mM MgCl2 concentrations respectively. Percentage increase in erythrocyte-bound bilirubin was found high...

  19. Functional induction of the cystine-glutamate exchanger system Xc(- activity in SH-SY5Y cells by unconjugated bilirubin.

    Directory of Open Access Journals (Sweden)

    Pablo J Giraudi

    Full Text Available We have previously reported that exposure of SH-SY5Y neuroblastoma cells to unconjugated bilirubin (UCB resulted in a marked up-regulation of the mRNA encoding for the Na(+-independent cystine∶glutamate exchanger System X(c(- (SLC7A11 and SLC3A2 genes. In this study we demonstrate that SH-SY5Y cells treated with UCB showed a higher cystine uptake due to a significant and specific increase in the activity of System X(c(-, without the contribution of the others two cystine transporters (X(AG(- and GGT reported in neurons. The total intracellular glutathione content was 2 folds higher in the cells exposed to bilirubin as compared to controls, suggesting that the internalized cystine is used for gluthathione synthesis. Interestingly, these cells were significantly less sensitive to an oxidative insult induced by hydrogen peroxide. If System X(c(- is silenced the protection is lost. In conclusion, these results suggest that bilirubin can modulate the gluthathione levels in neuroblastoma cells through the induction of the System X(c(-, and this renders the cell less prone to oxidative damage.

  20. Preparation of Aminated Macroporous Polyvinyl Alcohol Resins and Evaluation for Bilirubin Adsorption

    Institute of Scientific and Technical Information of China (English)

    WANG Wei-chao; ZHANG Sheng-nan; HU Yue-han; XIE Hui; OU Lai-liang; YU Yao-ting; KONG De-ling; GU Han-qing

    2008-01-01

    In the present study we prepared macroporous polyvinyl alcohol beads. A series of bilirubin adsorbents were generated by immobilization of eight amine agents to the beads as ligands. The adsorption of bilirubin was evaluated by in vitro static and dynamic adsorption tests. The results show that these adsorbents have excellent adsorption efficiency and capacity. Among the eight ligands, trimethylamine (TMA), triethylamine (TEA) and 1,6- hexanediamine(HAD) showed the highest adsorption capacity. The adsorption equilibrium can be achieved in half an hour, and the adsorption percentage of bilirubin was up to 80%. Static electricity and hydrophobic interaction played the main role in bilirubin adsorption, and the adsorption was found to match the monolayer model. The excellent adsorption of these adsorbents indicates their potential in clinical treatment.

  1. 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.

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

    Directory of Open Access Journals (Sweden)

    Shivanand Gamanagatti

    2016-01-01

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

  3. The effect of bilirubin on lipid peroxidation and antioxidant enzymes in cumene hydroperoxide-treated erythrocytes.

    Science.gov (United States)

    Yeşilkaya, A; Yeğin, A; Ozdem, S; Aksu, T A

    1998-01-01

    Recently, it has been suggested that bilirubin may act as a potent biological chain-breaking antioxidant. To observe the effects of free bilirubin on antioxidant reactions in cumene hydroperoxide-treated erythrocytes (15 g hemoglobin/dl), we added bilirubin at four different concentrations (0.5, 1, 5, and 10 mg/dl). We measured the thiobarbituric acid-reactive substance and reduced glutathione levels, and some antioxidant enzyme activities, namely superoxide dismutase, catalase, and glucose-6-phosphate dehydrogenase. Thiobarbituric acid-reactive substance and chemiluminescent signals decreased during the incubation. Superoxide dismutase activities also decreased but not as much as in the control group. Glucose-6-phosphate dehydrogenase activities and reduced glutathione levels increased, but catalase activities remained the same as the control group. Our results suggest that bilirubin--in the concentrations we have used--partially prevented the oxidant effects of cumene hydroperoxide.

  4. Serum bilirubin levels, UGT1A1 polymorphisms and risk for coronary artery disease.

    Science.gov (United States)

    Lingenhel, Arno; Kollerits, Barbara; Schwaiger, Johannes P; Hunt, Steven C; Gress, Richard; Hopkins, Paul N; Schoenborn, Veit; Heid, Iris M; Kronenberg, Florian

    2008-12-01

    Low levels of the antioxidative serum bilirubin are associated with vascular aging and an increased risk for coronary artery disease (CAD). UGT1A1 is the major gene influencing bilirubin concentrations. Therefore, we investigated an association of bilirubin levels and two polymorphisms in the promoter of UGT1A1 (-53(TA-repeat) polymorphism and T-3279G) in 477 patients with premature, familial CAD and 619 age- and sex-matched controls. Bilirubin concentrations were significantly lower in cases than in controls (0.62+/-0.36 vs. 0.76+/-0.41 mg/dl for men, p=1.2 x 10(-10); and 0.42+/-0.29 vs. 0.55+/-0.23 mg/dl, p=1.9 x 10(-9) for women). Both polymorphisms showed a strong association with bilirubin levels with higher levels for homozygote carriers of the minor allele. These associations were most pronounced in male controls and patients (p=5.9 x 10(-26) and p=3.4 x 10(-16), respectively, for the -53(TA-repeat) polymorphism). Logistic regression analysis revealed low bilirubin levels but not the UGT1A1 polymorphisms to be significantly associated with CAD: OR (95% CI) 0.90 (0.86-0.94), p=2.6 x 10(-6) for men and 0.77 (0.68-0.87), p=3.2 x 10(-5) for women, respectively for each 0.1mg/dl increase of bilirubin. These results indicate that it is rather decreased bilirubin levels in general than the changes in the genetic variation of this gene that increase the risk for CAD.

  5. Evaluation of oxidant and antioxidant status in term neonates: a plausible protective role of bilirubin.

    Science.gov (United States)

    Shekeeb Shahab, M; Kumar, Praveen; Sharma, Neeraj; Narang, Anil; Prasad, Rajendra

    2008-10-01

    In vitro studies have shown unequivocally that bilirubin is an antioxidant. We hypothesized that bilirubin serves a physiological role of an antioxidant in vivo. To investigate the probable protective role of bilirubin in vivo, term babies with clinical jaundice were grouped into four categories-serum total bilirubin (STB) 200 mg/l, and kernicterus. Serum bilirubin, serum albumin, plasma glucose-6-phosphate dehydrogenase (G6PD), lipid peroxidation in blood cells, and reduced glutathione (GSH) content in whole blood were investigated. We also measured superoxide dismutase (SOD) and catalase in hemolysate and total plasma antioxidant capacity (TAC). Lipid peroxidation and antioxidant enzymes were significantly lower in babies with STB 200 mg/l and in babies with bilirubin encephalopathy. Elevated levels of MDA, SOD, and catalase and significantly decreased levels of reduced glutathione and total antioxidant capacity were observed in STB >200 mg/l group. Antioxidant enzymes were also significantly inhibited in bilirubin encephalopathy babies. Post phototherapy, MDA production and antioxidant levels were significantly increased whilst total antioxidant capacity and reduced glutathione were significantly decreased compared to pre-phototherapy values. Exchange transfusion resulted in reduced oxidative stress in subjects with encephalopathy, whereas no significant difference was observed in other babies with STB >200 mg/l. Taken together, the present study propounds that bilirubin acts as a physiological antioxidant till 200 mg/l concentration in full-term normal neonates. It is conjectured that beyond 200 mg/l, it can no longer be considered physiologic. However, the cause of pathological jaundice needs to be identified and treated. The present data documents that phototherapy also induces oxidative stress.

  6. Studies on The Adsorption Capacity for Bilirubin of The Adsorbent Chitosan-β-Cyclodextrin

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The adsorbent crosslinked chitosan-β-cyclodextrin (β-CD) was prepared by the reaction of glutaraldehyde with chitosan and β-cyclodextrin. This type of adsorbent has high adsorption capacity for unconjugated bilirubin. The adsorption capacity was related to the β-CD content of the adsorbent; phosphate buffer concentration; temperature; pH value; ionic strength and the adsorbent beads. The results indicated that the chitosan-β-CD was a good adsorbent for unconjugated bilirubin with high capacity.

  7. Quantitative determination of cerebrospinal fluid bilirubin on a high throughput chemistry analyzer

    OpenAIRE

    Said Ahmed, Degmo

    2009-01-01

    Background Subarachnoid hemorrhage is a condition with high rates of mortality and morbidity. The diagnosis requires an urgent cerebral computed tomography scan and also a lumbar puncture if the scan fails to demonstrate intracranial blood. In Sweden the cerebrospinal fluid (CSF) is analyzed by spectrophotometric scanning for the presence of hemoglobin and bilirubin. The aim of the study was to develop a quantitative diazo reagent based analysis of cerebrospinal fluid bilirubin as a replaceme...

  8. Successive determination of urinary bilirubin and creatinine employing simultaneous injection effective mixing flow analysis.

    Science.gov (United States)

    Ponhong, Kraingkrai; Teshima, Norio; Grudpan, Kate; Vichapong, Jitlada; Motomizu, Shoji; Sakai, Tadao

    2015-02-01

    A novel four-channel simultaneous injection effective mixing flow analysis (SIEMA) system has been assembled for successive determination of bilirubin and creatinine in urinary samples. The chemical variables and physical parameters in the flow system were optimized for the enhancement of successive analytical performances. The interferences from urine matrices on the determination of bilirubin and creatinine were eliminated to dilute urine samples. The calibration graphs with the optimum conditions were achieved to be in 0.024-5.0 mg L(-1) for bilirubin and 2-100 mg L(-1) for creatinine. The relative standard deviations (RSDs) at 3 mg L(-1) of bilirubin and at 50 mg L(-1) of creatinine for 11 runs were 1.5 and 1.0%, respectively. The limits of detections (3σ of blank) for bilirubin and creatinine were 7 µg L(-1) and 0.6 mg L(-1), respectively. The sample throughput for stepwise detection was 22 h(-1). The proposed method was applied to the successive determination of bilirubin and creatinine in urine samples.

  9. Visual Impairment

    Science.gov (United States)

    ... Loss Surgery? A Week of Healthy Breakfasts Shyness Visual Impairment KidsHealth > For Teens > Visual Impairment Print A ... with the brain, making vision impossible. What Is Visual Impairment? Many people have some type of visual ...

  10. 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.

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

    Science.gov (United States)

    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.

  12. Study on the Property of β -CDEP Supported by Methylated Polystyrene for Inclusion and Adsorption of Bilirubin

    Institute of Scientific and Technical Information of China (English)

    MAO LuYuan; SHEN HanXi; ZHUANG YunFeng; YANG Yong; FAN YunGe

    2001-01-01

    @@ How to utilize functional material to eliminate uncombined bilirubin is a key problem in the research of artificial hepatic supporter [1]. There have been reports on the utilization of cyclodextrin and its polymer as biomedical materials [2,3]. In this paper, it was studied that the property of cyclodextrin polymers (MPS-CDEP) synthesized by us for the inclusion and adsorption of bilirubin. Bilirubin is the degradation product of heme (ferriprotoporohyrin IX), which body contain, and structures of both as follows:

  13. The relationship of the anti-oxidant bilirubin with free thyroxine is modified by insulin resistance in euthyroid subjects.

    Directory of Open Access Journals (Sweden)

    Petronella E Deetman

    Full Text Available BACKGROUND: The strong anti-oxidative properties of bilirubin largely explain its cardioprotective effects. Insulin resistance is featured by low circulating bilirubin. Thyroid hormone affects both bilirubin generation and its biliary transport, but it is unknown whether circulating bilirubin is associated with thyroid function in euthyroid subjects. Aim is to determine relationships of bilirubin with TSH, free T4 and free T3 in euthyroid subjects without type 2 diabetes mellitus (T2DM, and to assess whether such a relationship would be modified by the degree of insulin resistance. METHODS: Total bilirubin, TSH, free T4, free T3, glucose, insulin, lipids and transaminases were measured in 1854 fasting euthyroid subjects without T2DM, recruited from the general population (PREVEND cohort. Insulin resistance was assessed by homeostasis model assessment. RESULTS: Bilirubin was positively related to free T4 (β = 0.116, P<0.001 and free T3 (β = 0.078, P = 0.001, but bilirubin was unrelated to TSH. The relationship of bilirubin with free T4 was modified by insulin resistance with a larger effect in more insulin resistant individuals (adjusted for age and sex: β = 0.043, P = 0.056 for interaction; additionally adjusted for smoking, alcohol intake, transaminases and total cholesterol (β = 0.044, P = 0.044 for interaction. The association of bilirubin with free T4 was also modified by high density lipoprotein cholesterol (age- and sex-adjusted: β = 0.040, P = 0.072. CONCLUSIONS: Low bilirubin relates to low free T4 in euthyroid non-diabetic subjects. Low normal free T4 may particularly confer low bilirubin in more insulin resistant individuals.

  14. 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.

  15. 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.

  16. Bilirubin degradation in methanol induced by continuous UV-B irradiation: a UHPLC--ESI-MS study.

    Science.gov (United States)

    Stanojević, J S; Zvezdanović, J B; Marković, D Z

    2015-04-01

    Degradation of bilirubin in aerobic methanol solution by continuous UV-B irradiation has been investigated in this work. The purpose of this study was to shed more light on bilirubin interaction with the UV-B component of natural sunlight, since bilirubin is a very efficient UV-B absorber located in the skin epidermis. The degradation products have been detected and studied by a combined method of Ultra High Performance Liquid Chromatography-Electrospray Ionization Mass Spectrometry (UHPLC-ESI-MS). Bilirubin, a toxic pigment which itself is a product of (hemoglobin) degradation in organisms, undergoes its own degradation under aerobic conditions of UV-B continuous irradiation (e.g. photooxidation) that can be partly self-sensitized. Two dipyrrolic structures have been identified as a result of the bilirubin degradation, not including the bilirubin derivative biliverdin whose increase in the irradiated system is synchronous with a time dynamics of bilirubin degradation. It appears that one of dipyrrolic products originates directly from bilirubin and biliverdin molecules, while the other one is probably connected to bilirubin self-sensitized degradation. The precursor role of biliverdin in the degradation process--related to the detected dipyrroles--has not been confirmed.

  17. Efficient voltammetric discrimination of free bilirubin from uric acid and ascorbic acid by a CVD nanographite-based microelectrode.

    Science.gov (United States)

    Taurino, Irene; Van Hoof, Viviane; Magrez, Arnaud; Forró, László; De Micheli, Giovanni; Carrara, Sandro

    2014-12-01

    We report a novel electrochemical sensor based on nanographite grown on platinum microelectrodes for the determination of bilirubin in the presence of normal concentrations of albumin. The albumin is a protein with an intrinsic ability to bind the bilirubin therefore reducing the concentration of the free electroactive metabolite in human fluids. In addition, the proposed device permits the discrimination of free bilirubin from two interferents, uric acid and ascorbic acid, by the separation of their oxidation peaks in voltammetry. Preliminary measurements in human serum prove that the proposed nanostructured platform can be used to detect bilirubin.

  18. Lower Serum Bilirubin and Uric Acid Concentrations in Patients with Parkinson's Disease in China.

    Science.gov (United States)

    Qin, Xiao-Ling; Zhang, Qing-Shan; Sun, Li; Hao, Meng-Wei; Hu, Zhao-Ting

    2015-05-01

    The objective of the study is to investigate the correlation between bilirubin and uric acid (UA) concentrations and symptoms of Parkinson's disease (PD) in Chinese population. A total of 425 PD patients and 460 controls were included in the current study. Patients were diagnosed by a neurologist and assessed using the Hoehn & Yahr (H&Y) scale. Venous blood samples were collected, and bilirubin and UA concentrations were analyzed. Compared to controls, indirect bilirubin (IBIL) and UA concentrations were lower in PD patients (P IBIL = 0.015, P UA = 0.000). Serum IBIL in different age subgroups and H&Y stage subgroups were also lower compared to the control group (P IBIL = 0.000, P UA = 0.000) but were not significantly different among these subgroups. Females in the control group had significantly lower serum IBIL and UA concentrations than males (P IBIL = 0.000, P UA = 0.000) and the PD group (P IBIL = 0.027, P UA = 0.000). In early PD (patients with bilirubin and UA concentrations lack the endogenous defense system to prevent peroxynitrite and other free radicals from damaging and destroying dopaminergic cells in the substantia nigra. Our results provide a basis for further investigation into the role of bilirubin in PD.

  19. Evaluation of region selective bilirubin-induced brain damage as a basis for a pharmacological treatment

    Science.gov (United States)

    Dal Ben, Matteo; Bottin, Cristina; Zanconati, Fabrizio; Tiribelli, Claudio; Gazzin, Silvia

    2017-01-01

    The neurologic manifestations of neonatal hyperbilirubinemia in the central nervous system (CNS) exhibit high variations in the severity and appearance of motor, auditory and cognitive symptoms, which is suggestive of a still unexplained selective topography of bilirubin-induced damage. By applying the organotypic brain culture (OBC: preserving in vitro the cellular complexity, connection and architecture of the in vivo brain) technique to study hyperbilirubinemia, we mapped the regional target of bilirubin-induced damage, demonstrated a multifactorial toxic action of bilirubin, and used this information to evaluate the efficacy of drugs applicable to newborns to protect the brain. OBCs from 8-day-old rat pups showed a 2–13 fold higher sensitivity to bilirubin damage than 2-day-old preparations. The hippocampus, inferior colliculus and cerebral cortex were the only brain regions affected, presenting a mixed inflammatory-oxidative mechanism. Glutamate excitotoxicity was appreciable in only the hippocampus and inferior colliculus. Single drug treatment (indomethacin, curcumin, MgCl2) significantly improved cell viability in all regions, while the combined (cocktail) administration of the three drugs almost completely prevented damage in the most affected area (hippocampus). Our data may supports an innovative (complementary to phototherapy) approach for directly protecting the newborn brain from bilirubin neurotoxicity. PMID:28102362

  20. A genome-wide association study of total bilirubin and cholelithiasis risk in sickle cell anemia.

    Directory of Open Access Journals (Sweden)

    Jacqueline N Milton

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

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

    Directory of Open Access Journals (Sweden)

    Silvia eGazzin

    2012-05-01

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

  2. Protein-encapsulated bilirubin: paving the way to a useful probe for singlet oxygen.

    Science.gov (United States)

    Pimenta, Frederico M; Jensen, Jan K; Etzerodt, Michael; Ogilby, Peter R

    2015-04-01

    When dissolved in a bulk solvent, bilirubin efficiently removes singlet molecular oxygen, O2(a(1)Δg), through a combination of chemical reactions and by promoting the O2(a(1)Δg)→O2(X(3)Σg(-)) nonradiative transition to populate the ground state of oxygen. To elucidate how such processes can be exploited in the development of a biologically useful fluorescent probe for O2(a(1)Δg), pertinent photophysical and photochemical parameters of bilirubin encapsulated in a protein were determined. The motivation for studying a protein-encapsulated system reflects the ultimate desire to (a) use genetic engineering to localize the probe at a specific location in a living cell, and (b) provide a controlled environment around the chromophore/fluorophore. Surprisingly, explicit values of oxygen- and O2(a(1)Δg)-dependent parameters that characterize the behavior of a given chromophore/fluorophore encased in a protein are not generally available. To the end of quantifying the effects of such an encasing protein, a recently discovered bilirubin-binding protein isolated from a Japanese eel was used. The data show that this system indeed preferentially responds to O2(a(1)Δg) and not to the superoxide ion. However, this protein not only shields bilirubin such that the rate constants for interaction with O2(a(1)Δg) decrease relative to what is observed in a bulk solvent, but the fraction of the total O2(a(1)Δg)-bilirubin interaction that results in a chemical reaction between O2(a(1)Δg) and bilirubin also decreases appreciably. The rate constants thus obtained provide a useful starting point for the general design and development of reactive protein-encased fluorescent probes for O2(a(1)Δg).

  3. 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

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

    Science.gov (United States)

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

    2012-07-01

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

  5. Bilirubin diglucuronide synthesis by a UDP-glucuronic acid-dependent enzyme system in rat liver microsomes.

    Science.gov (United States)

    Blanckaert, N; Gollan, J; Schmid, R

    1979-01-01

    Incubation of rat liver homogenate or microsomal preparations with bilirubin or bilirubin monoglucuronide with (BMG) resulted in formation of bilirubin diglucuronide (BDG). Both synthesis of BMG and its conversion to BDG were critically dependent on the presence of UDP-glucuronic acid. Pretreatment of the animals with phenobarbital stimulated both reactions. When 33 microM bilirubin was incubated with microsomal preparations from phenobarbital-treated rats, 80-90% of the substrate was converted to bilirubin glucuronides; the reaction products consisted of almost equal amounts of BMG and BDG. When phenobarbital pretreatment was omitted or when the substrate concentration was increased to 164 microM bilirubin, proportionally more BMG and less BDG were formed. Homogenate and microsomes from homozygous Gunn rats neither synthesized BMG nor converted BMG to BDG. These findings in vitro suggest an explanation for the observations in vivo that, in conditions of excess bilirubin load or of genetically decreased bilirubin UDP glucuronosyltransferase (EC 2.4.1.17) activity, proportionally more BMG and less BDG are excreted in bile. PMID:109837

  6. 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

    2016-01-01

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

  7. Evaluation of the Predictive Value of Umbilical Cord Serum Bilirubin Level for the Development of Subsequent Hyperbilirubinemia in Term and Late-Preterm Neonates

    Directory of Open Access Journals (Sweden)

    Fariba Hemmati

    2016-03-01

    Conclusion: Based on the findings, UCS bilirubin level could not predict subsequent hyperbilirubinemia. Therefore, the best predictive marker for neonatal jaundice is the assessment of clinical risk factors and predischarge bilirubin level.

  8. Microchip capillary electrophoresis for frontal analysis of free bilirubin and study of its interaction with human serum albumin.

    Science.gov (United States)

    Nie, Zhou; Fung, Ying Sing

    2008-05-01

    To meet the need for bedside monitoring of free bilirubin for neonates under critical conditions, a microfluidic chip was fabricated and tested for its coupling with CE/frontal analysis (FA) to determine free bilirubin and study of its binding interaction with HSA, which regulated its concentration in plasma. The poly(methyl methacrylate) (PMMA) multichannel chip was fabricated by CO2 laser ablation and bonded with a fused-silica separation capillary for CE/FA separation with UV detection. The chip was designed to allow a complete assay of four electrophoretic runs using preconditioned channels to speed up the determination of free bilirubin and to deliver quick results for bedside monitoring. Under optimized conditions, the linear working range for free bilirubin was from 10 to 200 micromol with RSDs from 2.1 to 5.0% for n=3, and the LOD at 9 micromol for S/N=3. From a binding study between bilirubin and HSA under FA condition, the second binding constant for bilirubin-HSA was determined as 1.07x10(5) L/mol and the number of binding sites per HSA as 3.46. The results enabled the calculation of free bilirubin for jaundiced infants based on the clinically significant level of total bilirubin, producing a range of 118.3-119.4 micromol/L. The developed method is shown to meet the clinical requirement with additional margin of protection to detect the early rising level of free bilirubin prior to jaundice condition. The low-cost microchip CE/FA device is shown to produce quick results with high potential to deliver a suitable bed-side monitoring method for bilirubin management in neonates.

  9. 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.

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

    Directory of Open Access Journals (Sweden)

    Christian V Hulzebos

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

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

    Directory of Open Access Journals (Sweden)

    Tanujjal Bora

    2013-11-01

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

  12. Preparation and adsorption property of aminated cross linking microbeads of GMA/EGDMA for bilirubin

    Indian Academy of Sciences (India)

    Zhiping Chen; Baojiao Gao; Xiaofeng Yang

    2009-11-01

    Cross linking microbeads with a controllable diameter were synthesized by suspension copolymerization of the monomer glycidyl methacrylate (GMA) and the cross linking agent ethylene glycol dimethylacrylate (EGDMA). By the ring-opening reaction of the epoxy groups, the microbeads GMA/EGDMA were modified with different aminating agents and resulting in the aminated microbeads. The morphology of the microbeads was characterized by SEM. The adsorption property of aminated microbeads for bilirubin was investigated, and the effects of various factors, such as the chemical structures of the aminating agents, pH values of the medium and the presence of bovine serum albumin in the adsorption medium, on the adsorption property were examined. The experimental results show that the aminated microbeads have strong adsorption ability for bilirubin, and the isotherm adsorption behaviour is fitted to Freundlich equation satisfactorily. The adsorption ability of the aminated microbeads modified with hexanediamine is stronger than that of others, and the longer the molecule of multi-ethylene multiamine, the weaker the adsorption ability for bilirubin. The pH value of the medium affects the adsorption ability greatly, as pH = 6, the adsorption ability is strongest. In the presence of BSA, the microbeads still have a higher adsorption capacity towards bilirubin.

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

    Science.gov (United States)

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

    2012-01-01

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

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

    Science.gov (United States)

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

    2016-06-01

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

  15. 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.

  16. Prognostic value of serum total bilirubin in patients with acute coronary syndrome after percutaneous coronary intervention

    Institute of Scientific and Technical Information of China (English)

    孙同文

    2013-01-01

    Objective To investigate the predictive value of serum total bilirubin (STB) level in patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI) .Methods A total of 1273 consecutive patients treated with PCI in cardiology department,First Affiliated Hospital of Zhengzhou University from June

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

    Energy Technology Data Exchange (ETDEWEB)

    Jin Gu [Department of Chemistry, University of Science and Technology of China, HeFei, 230026 (China)], E-mail: Gjin@ustc.edu.cn; Yao Qizhi; Zhang Shanzi [Department of Chemistry, University of Science and Technology of China, HeFei, 230026 (China); Zhang Lei [Department of Chemistry, University of Science and Technology of China, HeFei, 230026 (China); AnHui Entry Exit Inspection and Quarantine Bureau, HeFei, 230001 (China)

    2008-12-01

    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.

  18. EKTACHEM bilirubin fraction Bc as a predictor of liver transplant rejection.

    Science.gov (United States)

    Cox, C J; Valdiserri, R O; Zerbe, T R; Genter, J L

    1987-10-01

    Bilirubin fractions Bc and DELTA, not routinely available prior to the EKTACHEM Chemistry Analyzer and its slide methodology, were studied in an outpatient population of liver transplant recipients. A preliminary evaluation by the authors has shown that direct bilirubin (DBILI) levels in the normal range consist almost exclusively of DELTA (protein-bound conjugated bilirubin), while at elevated DBILI levels, an increasing amount of Bc (non-protein-bound conjugated bilirubin) is measured as well. The present study evaluated the clinical significance of Bc in the serum of 80 liver transplant recipients as a means of identifying episodes of rejection. Each patient was classified into rejection or nonrejection categories based on clinical status, liver biopsy results, and/or response to therapy. Eighteen patients were classified as experiencing an episode of rejection during the period of this study. Fourteen of these (77.8%) had Bc levels that ranged from 0.1 to 6.8 mg/dl. Sixty two patients were classified in the nonrejection category. Fourteen (22.6%) of these patients had Bc levels that ranged from 0.1 to 0.6 mg/dl. In our outpatient liver transplant recipients with Bc greater than or equal to 0.1 mg/dl, the relative risk of rejection (% of rejection patients with Bc/% of nonrejection patients with Bc) was 3.44. This value indicates that Bc determination may be a helpful adjunct in the assessment of rejection.

  19. 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 Section 862.1110 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry...

  20. A pro-inflammatory glycoprotein biomarker is associated with lower bilirubin in metabolic syndrome

    NARCIS (Netherlands)

    Dullaart, Robin P. F.; Gruppen, Eke G.; Connelly, Margery A.; Lefrandt, Joop D.

    2015-01-01

    Objectives: Bilirubin exerts anti-oxidative and anti-inflammatory properties which may beneficially influence the development of cardio-metabolic disorders. A nuclear magnetic resonance (NMR) spectroscopy-based glycoprotein biomarker, designated GlycA, whose signal originates from several glycosylat

  1. Association between antiretroviral exposure and renal impairment among HIV-positive persons with normal baseline renal function : the D:A:D study

    NARCIS (Netherlands)

    Ryom, Lene; Mocroft, Amanda; Kirk, Ole; Worm, Signe W; Kamara, David A; Reiss, Peter; Ross, Michael; Fux, Christoph A; Morlat, Philippe; Moranne, Olivier; Smith, Colette; Lundgren, Jens D; Schölvinck, Elisabeth H.

    2013-01-01

    BACKGROUND: Several antiretroviral agents (ARVs) are associated with chronic renal impairment, but the extent of such adverse events among human immunodeficiency virus (HIV)-positive persons with initially normal renal function is unknown. METHODS: D:A:D study participants with an estimated glomerul

  2. Assessment of duodenogastric reflux by combined continuous intragastric pH and bilirubin monitoring

    Institute of Scientific and Technical Information of China (English)

    Fei Dai; Jun Gong; Ru Zhang; Jin-Yan Luo; You-Ling Zhu; Xue-Qin Wang

    2002-01-01

    AIM: To assess the diagnostic value of a combination of continuous intragastric pH and bilirubin monitoring in the detection of duodenogastric reflux (DGR), and the effects of diet on the bilirubin absorbance.METHODS: 30 healthy volunteers were divided into twogroups: standard diet group (Group 1) 18 cases, free diet group (Group 2) 12 cases. Each subjects were subjected to simultaneous 24 hour intragastric pH and spectrophotometric bilirubin concentration monitoring (Bilitec 2000).RESULTS: There was no difference of preprandial phasebilirubin absorbance between two groups. The absorbanceof postprandial phase was significantly increased in group 2than group 1. There was no difference between preprandialphase and postprandial phase absorbance in group 1.Postprandial phase absorbance was significantly higher ingroup 2. In a comparison of bile reflux with intragastric pHduring night time, there were 4 types of reflux:Simultaneous increase in absorbance and pH in only 19.6%, increase in bilirubin with unchanged pH 33. 3 %, pHincrease with unchanged absorbance 36. 3 %, and bothunchanged in 10. 8 %. Linear regression analysis showed nocorrelation between percertage total time of pH < 4 aridpercentage total time of absortance > 0. 14, r=0.068, P<0.05.CONCLUSION: Because of the dietary effect, highabsorbance fluids or foods should be avoided in detection.Intrsgastric pH and bilirubin monitoring separately predictthe presence of duodenal (and/or pancreatic) reflux and bilereflux. They can not substitute for each other. The detectionof DGR is improved if the two parameters are combinedsimultanoously.

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

    Science.gov (United States)

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

    2014-11-15

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

  4. Gulf War agent exposure causes impairment of long-term memory formation and neuropathological changes in a mouse model of Gulf War Illness.

    Directory of Open Access Journals (Sweden)

    Zuchra Zakirova

    Full Text Available Gulf War Illness (GWI is a chronic multisymptom illness with a central nervous system component such as memory deficits, neurological, and musculoskeletal problems. There are ample data that demonstrate that exposure to Gulf War (GW agents, such as pyridostigmine bromide (PB and pesticides such as permethrin (PER, were key contributors to the etiology of GWI post deployment to the Persian GW. In the current study, we examined the consequences of acute (10 days exposure to PB and PER in C57BL6 mice. Learning and memory tests were performed at 18 days and at 5 months post-exposure. We investigated the relationship between the cognitive phenotype and neuropathological changes at short and long-term time points post-exposure. No cognitive deficits were observed at the short-term time point, and only minor neuropathological changes were detected. However, cognitive deficits emerged at the later time point and were associated with increased astrogliosis and reduction of synaptophysin staining in the hippocampi and cerebral cortices of exposed mice, 5 months post exposure. In summary, our findings in this mouse model of GW agent exposure are consistent with some GWI symptom manifestations, including delayed onset of symptoms and CNS disturbances observed in GWI veterans.

  5. In utero exposure to prepregnancy maternal obesity and postweaning high-fat diet impair regulators of mitochondrial dynamics in rat placenta and offspring

    OpenAIRE

    Borengasser, Sarah J.; Faske, Jennifer; KANG, PING; Blackburn, Michael L.; Badger, Thomas M.; Shankar, Kartik

    2014-01-01

    The proportion of pregnant women who are obese at conception continues to rise. Compelling evidence suggests the intrauterine environment is an important determinant of offspring health. Maternal obesity and unhealthy diets are shown to promote metabolic programming in the offspring. Mitochondria are maternally inherited, and we have previously shown impaired mitochondrial function in rat offspring exposed to maternal obesity in utero. Mitochondrial health is maintained by mitochondrial dynam...

  6. Exposure of BALB/c Mice to Diesel Engine Exhaust Origin Secondary Organic Aerosol (DE-SOA) during the Developmental Stages Impairs the Social Behavior in Adult Life of the Males.

    Science.gov (United States)

    Win-Shwe, Tin-Tin; Kyi-Tha-Thu, Chaw; Moe, Yadanar; Fujitani, Yuji; Tsukahara, Shinji; Hirano, Seishiro

    2015-01-01

    Secondary organic aerosol (SOA) is a component of particulate matter (PM) 2.5 and formed in the atmosphere by oxidation of volatile organic compounds. Recently, we have reported that inhalation exposure to diesel engine exhaust (DE) originated SOA (DE-SOA) affect novel object recognition ability and impair maternal behavior in adult mice. However, it is not clear whether early life exposure to SOA during the developmental stages affect social behavior in adult life or not. In the present study, to investigate the effects of early life exposure to DE-SOA during the gestational and lactation stages on the social behavior in the adult life, BALB/c mice were exposed to clean air (control), DE, DE-SOA and gas without any PM in the inhalation chambers from gestational day 14 to postnatal day 21 for 5 h a day and 5 days per week. Then adult mice were examined for changes in their social behavior at the age of 13 week by a sociability and social novelty preference, social interaction with a juvenile mouse and light-dark transition test, hypothalamic mRNA expression levels of social behavior-related genes, estrogen receptor-alpha and oxytocin receptor as well as of the oxidative stress marker gene, heme oxygenase (HO)-1 by real-time RT-PCR method. In addition, hypothalamic level of neuronal excitatory marker, glutamate was determined by ELISA method. We observed that sociability and social novelty preference as well as social interaction were remarkably impaired, expression levels of estrogen receptor-alpha, oxytocin receptor mRNAs were significantly decreased, expression levels of HO-1 mRNAs and glutamate levels were significantly increased in adult male mice exposed to DE-SOA compared to the control ones. Findings of this study indicate early life exposure of BALB/c mice to DE-SOA may affect their late-onset hypothalamic expression of social behavior related genes, trigger neurotoxicity and impair social behavior in the males.

  7. Exposure of BALB/c mice to diesel engine exhaust origin secondary organic aer-osol (DE-SOA during the developmental stages impairs the social behavior in adult life of the males

    Directory of Open Access Journals (Sweden)

    Tin-Tin eWin-Shwe

    2016-01-01

    Full Text Available Secondary organic aerosol (SOA is a component of particulate matter (PM 2.5 and formed in the atmosphere by oxidation of volatile organic compounds. Recently, we have reported that inhalation exposure to diesel engine exhaust (DE originated SOA (DE-SOA affect novel object recognition ability and impair maternal behavior in adult mice. However, it is not clear whether early life exposure to SOA during the de-velopmental stages affect social behavior in adult life or not. In the present study, to investigate the effects of early life exposure to DE-SOA during the gestational and lactation stages on the social behavior in the adult life, BALB/c mice were exposed to clean air (control, DE, DE-SOA and gas without any particulate matter in the inhala-tion chambers from gestational day 14 to postnatal day 21 for 5 h a day and 5 days per week. Then adult mice were examined for changes in their social behavior at the age of 13 week by a sociability and social novelty preference, social interaction with a juvenile mouse and light-dark transition test, hypothalamic mRNA expression levels of social behavior-related genes, estrogen receptor-alpha and oxytocin receptor as well as of the oxidative stress marker gene, heme oxygenase (HO-1 by real-time RT-PCR method. In addition, hypothalamic level of neuronal excitatory marker, glutamate was determined by ELISA method. We observed that sociability and social novelty pref-erence as well as social interaction were remarkably impaired, expression levels of es-trogen receptor-alpha, oxytocin receptor mRNAs were significantly decreased, ex-pression levels of HO-1 mRNAs and glutamate levels were significantly increased in adult male mice exposed to DE-SOA compared to the control ones. Findings of this study indicate early life exposure of BALB/c mice to DE-SOA may affect their late-onset hypothalamic expression of social behavior related genes, trigger neurotoxi-city and impair social behavior in the males.

  8. 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 (CO2) 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.

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

    Science.gov (United States)

    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.

  10. Impaired terrestrial and arboreal locomotor performance in the western fence lizard (Sceloporus occidentalis) after exposure to an AChE-inhibiting pesticide

    Energy Technology Data Exchange (ETDEWEB)

    DuRant, Sarah E. [Wildlife Ecotoxicology and Physiological Ecology Program, Department of Fisheries and Wildlife Sciences, Virginia Polytechnic Institute and State University, 444 Latham Hall, Blacksburg, VA 24061 (United States); University of Georgia, Savannah River Ecology Laboratory, PO Drawer E, Aiken, SC 29802 (United States); Hopkins, William A. [Wildlife Ecotoxicology and Physiological Ecology Program, Department of Fisheries and Wildlife Sciences, Virginia Polytechnic Institute and State University, 444 Latham Hall, Blacksburg, VA 24061 (United States) and University of Georgia, Savannah River Ecology Laboratory, PO Drawer E, Aiken, SC 29802 (United States)]. E-mail: hopkinsw@vt.edu; Talent, Larry G. [Department of Zoology, Oklahoma State University, Stillwater, OK 74078 (United States)

    2007-09-15

    We examined the effects of a commonly used AChE-inhibiting pesticide on terrestrial and arboreal sprint performance, important traits for predator avoidance and prey capture, in the western fence lizard (Sceloporus occidentalis). Lizards were exposed to carbaryl (2.5, 25, and 250 {mu}g/g) and were raced before and 4, 24, and 96 h after dosing. In the terrestrial setting, exposure to low concentrations of carbaryl had stimulatory effects on performance, but exposure to the highest concentration was inhibitory. No stimulatory effects of carbaryl were noted in the arboreal environment and performance in lizards was reduced after exposure to both the medium and highest dose of carbaryl. Our findings suggest that acute exposure to high concentrations of carbaryl can have important sublethal consequences on fitness-related traits in reptiles and that arboreal locomotor performance is a more sensitive indicator of AChE-inhibiting pesticide poisoning than terrestrial locomotor performance. - Exposure to an acetylcholinesterase-inhibiting pesticide alters locomotor performance in western fence lizards.

  11. Pre-exposure of Mycobacterium tuberculosis-infected macrophages to crystalline silica impairs control of bacterial growth by deregulating the balance between apoptosis and necrosis.

    Directory of Open Access Journals (Sweden)

    Leslie Chávez-Galán

    Full Text Available Inhalation of crystalline silica (CS particles increases the risk of pulmonary tuberculosis; however, the precise mechanism through which CS exposure facilitates Mycobacterium tuberculosis (Mtb infection is unclear. We speculate that macrophage exposure to CS deregulates the cell death pathways that could explain, at least in part, the association observed between exposure to CS and pulmonary tuberculosis. We therefore established an in vitro model in which macrophages were exposed to CS and then infected with Mtb. Expression of surface markers was analyzed by flow cytometry, JNK1/2, ASK1, caspase 9, P-p38, Bcl-2 and Mcl-1 were analyzed by Western blot, and cytokines by ELISA. Our results show that exposure to CS limits macrophage ability to control Mtb growth. Moreover, this exposure reduced the expression of TLR2, Bcl-2 and Mcl-1, but increased that of JNK1 and ASK1 molecules in the macrophages. Finally, when the pre-exposed macrophages were infected with Mtb, the concentrations of TNFα, IL-1β and caspase-9 expression increased. This pro-inflammatory profile of the macrophage unbalanced the apoptosis/necrosis pathway. Taken together, these data suggest that macrophages exposed to CS are sensitized to cell death by MAPK kinase-dependent signaling pathway. Secretion of TNF-α and IL-1β by Mtb-infected macrophages promotes necrosis, and this deregulation of cell death pathways may favor the release of viable bacilli, thus leading to the progression of tuberculosis.

  12. Looking to the horizon: the role of bilirubin in the development and prevention of age-related chronic diseases.

    Science.gov (United States)

    Wagner, Karl-Heinz; Wallner, Marlies; Mölzer, Christine; Gazzin, Silvia; Bulmer, Andrew Cameron; Tiribelli, Claudio; Vitek, Libor

    2015-07-01

    Bilirubin, the principal tetrapyrrole, bile pigment and catabolite of haem, is an emerging biomarker of disease resistance, which may be related to several recently documented biological functions. Initially believed to be toxic in infants, the perception of bilirubin has undergone a transformation: it is now considered to be a molecule that may promote health in adults. Data from the last decade demonstrate that mildly elevated serum bilirubin levels are strongly associated with reduced prevalence of chronic diseases, particularly cardiovascular diseases (CVDs), as well as CVD-related mortality and risk factors. Recent data also link bilirubin to other chronic diseases, including cancer and Type 2 diabetes mellitus, and to all-cause mortality. Therefore, there is evidence to suggest that bilirubin is a biomarker for reduced chronic disease prevalence and a predictor of all-cause mortality, which is of important clinical significance. In the present review, detailed information on the association between bilirubin and all-cause mortality, as well as the pathological conditions of CVD, cancer, diabetes and neurodegenerative diseases, is provided. The mechanistic background concerning how bilirubin and its metabolism may influence disease prevention and its clinical relevance is also discussed. Given that the search for novel biomarkers of these diseases, as well as for novel therapeutic modalities, is a key research objective for the near future, bilirubin represents a promising candidate, meeting the criteria of a biomarker, and should be considered more carefully in clinical practice as a molecule that might provide insights into disease resistance. Clearly, however, greater molecular insight is warranted to support and strengthen the conclusion that bilirubin can prevent disease, with future research directions also proposed.

  13. Bilirubin activates transcription of HIF-1α in human proximal tubular cells cultured in the physiologic oxygen content.

    Science.gov (United States)

    Kim, Sung Gyun; Ahn, Shin-Young; Lee, Eun Seong; Kim, Sejoong; Na, Ki Young; Chae, Dong-Wan; Chin, Ho Jun

    2014-09-01

    The expression of hypoxia-inducible factor (HIF) is influenced by reactive oxygen species (ROS). Effect of bilirubin on HIF-1 expression in proximal tubular cells was investigated under physiological oxygen concentration, which is relative hypoxic condition mimicking oxygen content in the medulla of renal tissue. The human kidney (HK2) cells were cultured in 5% oxygen with or without bilirubin. HIF-1α protein expression was increased by bilirubin treatment at 0.01-0.2 mg/dL concentration. The messenger RNA expression of HIF-1α was increased by 1.69±0.05 folds in the cells cultured with 0.1 mg/dL bilirubin, compared to the control cells. The inhibitors of PI3K/mTOR, PI3K/AKT, and ERK 1/2 pathways did not attenuate increased HIF-1α expression by bilirubin. HIF-1α expression decreased by 10 µM exogenous hydrogen peroxide (H2O2); scavenger of ROS with or without bilirubin in the HK2 cells increased HIF-1α concentration more than that in the cells without bilirubin. Exogenous H2O2 decreased the phosphorylation of P70S6 kinase, which was completely reversed by bilirubin treatment. Knockdown of NOX4 gene by small interfering RNA (siRNA) increased HIF-1α mRNA expression. In coonclusion, bilirubin enhances HIF-1α transcription as well as the up-regulation of HIF-1α protein translation through the attenuation of ROS and subunits of NADPH oxidase.

  14. 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.

  15. Gene therapy with bilirubin-UDP-glucuronosyltransferase in the Gunn rat model of Crigler-Najjar syndrome type 1.

    Science.gov (United States)

    Li, Q; Murphree, S S; Willer, S S; Bolli, R; French, B A

    1998-03-01

    Crigler-Najjar syndrome type 1 (CN type 1) is an autosomal recessive disorder characterized by nonhemolytic jaundice resulting from mutations to the gene encoding bilirubin-UDP-glucuronosyltransferase (UDPGT). The Gunn rat is an accurate animal model of this disease because the bilirubin-UDPGT gene in this strain carries a premature stop codon. The primary objective of this study was to complement this deficiency in vivo using liver-directed gene therapy. The efficiency of adenovirus type 5 (Ad5)-mediated gene transfer to the neonatal rat liver was first assessed by intravenous (i.v.) injection of an Ad5 vector carrying a nuclear-localized LacZ gene. An Ad5 vector expressing the cDNA encoding human bilirubin-UDPGT (Ad5/CMV/hUG-Br1) was then generated and injected i.v. into neonatal Gunn rats. Plasma samples were collected and bilirubin levels were determined at regular intervals. Although the mean level of bilirubin in homozygous Gunn rats 1-2 days after birth was already 14.5-fold higher than that of heterozygous siblings, treatment with Ad5/CMV/hUG-Br1 reduced plasma bilirubin to normal levels within 1 week. Plasma bilirubin in the treated homozygous rats remained normal for 4 weeks before gradually climbing to intermediate levels that were approximately half that of untreated homozygotes by 12 weeks. Administration of Ad5-mediated gene therapy to neonatal Gunn rats effectively complemented the deficiency in bilirubin-UDPGT, resulting in substantial reductions in plasma bilirubin over a 3-month period. The efficacy of Ad5-mediated gene therapy in neonates suggests that this approach might be effective against other hepatic disorders, including autosomal recessive deficiencies in lipid metabolism and vascular homeostasis.

  16. Mildly elevated serum bilirubin levels are negatively associated with carotid atherosclerosis among elderly persons.

    Directory of Open Access Journals (Sweden)

    Ryuichi Kawamoto

    Full Text Available 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, p < 0.001, systolic blood pressure (β = 0.104, p = 0.046, diastolic blood pressure (β = -0.148, p = 0.004, prevalence of antihypertensive medication (β = 0.126, p = 0.004, fasting plasma glucose (β = 0.135, p = 0.003, GGT (β = -0.104, p = 0.032, estimated glomerular filtration rate, serum bilirubin (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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-11-15

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

  18. In utero exposure to prepregnancy maternal obesity and postweaning high-fat diet impair regulators of mitochondrial dynamics in rat placenta and offspring.

    Science.gov (United States)

    Borengasser, Sarah J; Faske, Jennifer; Kang, Ping; Blackburn, Michael L; Badger, Thomas M; Shankar, Kartik

    2014-12-01

    The proportion of pregnant women who are obese at conception continues to rise. Compelling evidence suggests the intrauterine environment is an important determinant of offspring health. Maternal obesity and unhealthy diets are shown to promote metabolic programming in the offspring. Mitochondria are maternally inherited, and we have previously shown impaired mitochondrial function in rat offspring exposed to maternal obesity in utero. Mitochondrial health is maintained by mitochondrial dynamics, or the processes of fusion and fission, which serve to repair damaged mitochondria, remove irreparable mitochondria, and maintain mitochondrial morphology. An imbalance between fusion and fission has been associated with obesity, insulin resistance, and reproduction complications. In the present study, we examined the influence of maternal obesity and postweaning high-fat diet (HFD) on key regulators of mitochondrial fusion and fission in rat offspring at important developmental milestones which included postnatal day (PND)35 (2 wk HFD) and PND130 (∼16 wk HFD). Our results indicate HFD-fed offspring had reduced mRNA expression of presenilin-associated rhomboid-like (PARL), optic atrophy (OPA)1, mitofusin (Mfn)1, Mfn2, fission (Fis)1, and nuclear respiratory factor (Nrf)1 at PND35, while OPA1 and Mfn2 remained decreased at PND130. Putative transcriptional regulators of mitochondrial dynamics were reduced in rat placenta and offspring liver and skeletal muscle [peroxisome proliferator-activated receptor gamma coactivator (PGC1)α, PGC1β, and estrogen-related receptor (ERR)α], consistent with indirect calorimetry findings revealing reduced energy expenditure and impaired fat utilization. Overall, maternal obesity detrimentally alters mitochondrial targets that may contribute to impaired mitochondrial health and increased obesity susceptibility in later life.

  19. Arsenic Exposure and Calpain-10 Polymorphisms Impair the Function of Pancreatic Beta-Cells in Humans: A Pilot Study of Risk Factors for T2DM

    Science.gov (United States)

    Díaz-Villaseñor, Andrea; Cruz, Laura; Cebrián, Arturo; Hernández-Ramírez, Raúl U.; Hiriart, Marcia; García-Vargas, Gonzálo; Bassol, Susana; Sordo, Monserrat; Gandolfi, A. Jay; Klimecki, Walter T.; López-Carillo, Lizbeth; Cebrián, Mariano E.; Ostrosky-Wegman, Patricia

    2013-01-01

    The incidence of type 2 diabetes mellitus (T2DM) is increasing worldwide and diverse environmental and genetic risk factors are well recognized. Single nucleotide polymorphisms (SNPs) in the calpain-10 gene (CAPN-10), which encodes a protein involved in the secretion and action of insulin, and chronic exposure to inorganic arsenic (iAs) through drinking water have been independently associated with an increase in the risk for T2DM. In the present work we evaluated if CAPN-10 SNPs and iAs exposure jointly contribute to the outcome of T2DM. Insulin secretion (beta-cell function) and insulin sensitivity were evaluated indirectly through validated indexes (HOMA2) in subjects with and without T2DM who have been exposed to a gradient of iAs in their drinking water in northern Mexico. The results were analyzed taking into account the presence of the risk factor SNPs SNP-43 and -44 in CAPN-10. Subjects with T2DM had significantly lower beta-cell function and insulin sensitivity. An inverse association was found between beta-cell function and iAs exposure, the association being more pronounced in subjects with T2DM. Subjects without T2DM who were carriers of the at-risk genotype SNP-43 or -44, also had significantly lower beta-cell function. The association of SNP-43 with beta-cell function was dependent on iAs exposure, age, gender and BMI, whereas the association with SNP-44 was independent of all of these factors. Chronic exposure to iAs seems to be a risk factor for T2DM in humans through the reduction of beta-cell function, with an enhanced effect seen in the presence of the at-risk genotype of SNP-43 in CAPN-10. Carriers of CAPN-10 SNP-44 have also shown reduced beta-cell function. PMID:23349674

  20. Arsenic exposure and calpain-10 polymorphisms impair the function of pancreatic beta-cells in humans: a pilot study of risk factors for T2DM.

    Directory of Open Access Journals (Sweden)

    Andrea Díaz-Villaseñor

    Full Text Available The incidence of type 2 diabetes mellitus (T2DM is increasing worldwide and diverse environmental and genetic risk factors are well recognized. Single nucleotide polymorphisms (SNPs in the calpain-10 gene (CAPN-10, which encodes a protein involved in the secretion and action of insulin, and chronic exposure to inorganic arsenic (iAs through drinking water have been independently associated with an increase in the risk for T2DM. In the present work we evaluated if CAPN-10 SNPs and iAs exposure jointly contribute to the outcome of T2DM. Insulin secretion (beta-cell function and insulin sensitivity were evaluated indirectly through validated indexes (HOMA2 in subjects with and without T2DM who have been exposed to a gradient of iAs in their drinking water in northern Mexico. The results were analyzed taking into account the presence of the risk factor SNPs SNP-43 and -44 in CAPN-10. Subjects with T2DM had significantly lower beta-cell function and insulin sensitivity. An inverse association was found between beta-cell function and iAs exposure, the association being more pronounced in subjects with T2DM. Subjects without T2DM who were carriers of the at-risk genotype SNP-43 or -44, also had significantly lower beta-cell function. The association of SNP-43 with beta-cell function was dependent on iAs exposure, age, gender and BMI, whereas the association with SNP-44 was independent of all of these factors. Chronic exposure to iAs seems to be a risk factor for T2DM in humans through the reduction of beta-cell function, with an enhanced effect seen in the presence of the at-risk genotype of SNP-43 in CAPN-10. Carriers of CAPN-10 SNP-44 have also shown reduced beta-cell function.

  1. 农药暴露对人体健康损害研究的文献计量分析%Bibliometric analysis on human health impairment induced by pesticide exposure

    Institute of Scientific and Technical Information of China (English)

    张超; 孙艺夺; 李钟华; 胡瑞法; 蔡金阳

    2016-01-01

    Human health impairment induced by pesticide exposure has become a hot research topic. In this study, a bibliometric analysis on 481 English articles indexed by Science Citation Index Expanded (SCI-E) and Social Sciences Citation Index (SSCI) in Web of Science, and 46 Chinese articles indexed by China National Knowledge Infrastructure (CNKI) has been conducted. Generally, the number of articles about the health impairment induced by pesticide exposure is increasing, and the developed countries represented by the United States of America play a dominant role in this research field. The case-control study, the cohort study and the cross-sectional study are the three major research types, and Logistic regression and linear regression are the two most commonly adopted quantitative research methods. The impairment effect induced by pesticide exposure on all the human body systems, especially the nerve system, the reproductive system, and the circulatory system are the major research areas, which have also become the hot research issues during the period of 2011 to 2015. Substantial articles have also analyzed the correlations between pesticide exposure and the human cancer as well as death. It is noteworthy that there is a large gap between China and the developed countries in terms of the research performance in the field of the health impairment induced by pesticide exposure.%农药暴露对人体的健康损害已成为热点研究课题。对 Web of Science平台中 Science Citation Index Expanded (SCI-E)和 Social Sciences Citation Index (SSCI)检索的481篇英文论文和中国知网(CNKI)收录的46篇中文论文进行了文献计量分析。农药暴露对健康损害的论文数量总体呈现上升趋势,而以美国为代表的发达国家在该方面研究中占据主导地位。病例对照研究、队列研究和横截面研究是该方面最主要研究类型,而 Logistic回归和线性回归是被采用最多的定量研究方法。农药暴露

  2. THE ROLE OF DIETARY PROPOLIS ON ALBUMINS AND BILIRUBIN CONTENT IN CHICKENS

    Directory of Open Access Journals (Sweden)

    Marcela Capcarová

    2013-12-01

    Full Text Available The present study was designed to determinate the effect of propolis as a feed additive on the serum bilirubin and albumin content of female and male chickens. Broiler chickens hybrid Hubbard JV (n=500 were divided into five groups in each gender (control – C and four experimental groups E1 – E4. Experimental chickens received a propolis extract in feed mixture in various doses (E1 – 150 mg/kg; E2 – 450 mg/kg; E3 – 600 mg/kg; E4 – 800 mg/kg. The group that received feed without propolis addition served as the control. Contents of albumin and bilirubin were determined with spectrophotometer. Supplementation of the diet with propolis in the dose of 600 mg/kg significantly (P<0.05 increased albumin content in male chickens. Propolis addition to diets may be a source for antioxidant capacity in human and animals.

  3. Increased conjugated bilirubin is sufficient to initiate screening for biliary atresia

    DEFF Research Database (Denmark)

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

    2015-01-01

    . This percentage value has caused diagnostic trouble over the years. The objective of the present study was to investigate the possibility of changing the recommendations. METHODS: This was a retrospective analysis of the medical records of children operated for biliary atresia in the 1993-2012 period. RESULTS......: During the period, 73 patients where operated with a portoenterostomy ad modum Kasai. Patients older than 84 days at the time of operation were excluded, 54 patients were available for analysis. Conjugated bilirubin in μmol/l and the percentage value were significantly above the DHMA threshold limit......: mean 129.7 μmol/l (42-334 μmol/l) and 73% (28-97%), respectively. CONCLUSION: The total amount of conjugated bilirubin above 20 μmol/l is sufficient to require further evaluation for biliary atresia. The percentage value is unnecessary and may cause confusion. FUNDING: none. TRIAL REGISTRATION...

  4. Effects of OATP -C gene polymorphisms and low-dose rifampicin on serum bilirubin level

    Institute of Scientific and Technical Information of China (English)

    WeiZHANG; Yi-jingHE; QingLI; Hong-haoZHOU

    2005-01-01

    AIM OATP-C is a liver-specific organic anion uptake transporter and shows high affinity for bilirubin uptaking. Rifampicin has been identified as a potent inhibitor of OATP-C both in vitro and in vivo. This study was set to determine the allele frequencies of OATP-C*1a', OATP-C*1b, and OATP-C* 15 in Chinese population, and secondly, to quantitate the contribution of the OATP-C gene polymorphisms and low-dose rifampicin adminstration to the serum bilirubin level in vivo. METHODS Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) and a novel tetreprimers method were used to identify OATP-C*1a, OATP-C*1b, and OATP-C*15 genotypes.

  5. The role of bilirubin in diabetes, metabolic syndrome, and cardiovascular diseases

    Directory of Open Access Journals (Sweden)

    Libor eVitek

    2012-04-01

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

  6. Influence of bilirubin and other antioxidants on nitrergic relaxation in the pig gastric fundus.

    Science.gov (United States)

    Colpaert, E E; Lefebvre, R A

    2000-03-01

    1. The influence of several antioxidants (bilirubin, urate, ascorbate, alpha-tocopherol, glutathione (GSH), Cu/Zn superoxide dismutase (SOD) and the manganese SOD mimic EUK-8) on nitrergic relaxations induced by either exogenous nitric oxide (NO; 10(-5) M) or electrical field stimulation (4 Hz; 10 s and 3 min) was studied in the pig gastric fundus. 2. Ascorbate (5x10(-4) M), alpha-tocopherol (4x10(-4) M), SOD (300 - 1000 u ml(-1)) and EUK-8 (3x10(-4) M) did not influence the relaxations to exogenous NO. In the presence of GSH (5x10(-4) M), the short-lasting relaxation to NO became biphasic, potentiated and prolonged. Urate (4x10(-4) M) and bilirubin (2x10(-4) M) also potentiated the relaxant effect of NO. None of the antioxidants influenced the electrically evoked relaxations. 3. 6-Anilino-5,8-quinolinedione (LY83583; 10(-5) M) had no influence on nitrergic nerve stimulation but nearly abolished the relaxant response to exogenous NO. Urate and GSH completely prevented this inhibitory effect, while it was partially reversed by SOD and bilirubin. Ascorbate, alpha-tocopherol and EUK-8 were without effect. 4. Hydroquinone (10(-4) M) did not affect the electrically induced nitrergic relaxations, but markedly reduced NO-induced relaxations. The inhibition of exogenous NO by hydroquinone was completely prevented by urate and GSH. SOD and ascorbate afforded partial protection, while bilirubin, EUK-8 and alpha-tocopherol were ineffective. 5. Hydroxocobalamin (10(-4) M) inhibited relaxations to NO by 50%, but not the electrically induced responses. Full protection versus this inhibitory effect was obtained with urate, GSH and alpha-tocopherol. 6. These results strengthen the hypothesis that several endogenous antioxidant defense mechanisms, enzymatic as well as non-enzymatic, might play a role in the nitrergic neurotransmission process.

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

    Directory of Open Access Journals (Sweden)

    Thomas eJansen

    2012-03-01

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

  8. The antioxidant effect of free bilirubin on cumene-hydroperoxide treated human leukocytes.

    Science.gov (United States)

    Yesilkaya, A; Altinayak, R; Korgun, D K

    2000-07-01

    To examine the antioxidant effect of bilirubin (BR) on leukocyte, we treated leukocytes obtained from healthy subjects with an oxidant and various concentrations of BR. High concentrations of BR decreased thiobarbituric acid reactive substances (TBARS) and catalase activities, increased superoxide dismutase (SOD) activity, but had no effect on glutathione (GSH) concentration. Our results showed that under physiological conditions, BR has an antioxidant effect only in high concentrations.

  9. Antioxidant potential of bilirubin-accelerated wound healing in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Ram, Mahendra; Singh, Vishakha; Kumar, Dhirendra; Kumawat, Sanjay; Gopalakrishnan, Anu; Lingaraju, Madhu C; Gupta, Priyanka; Tandan, Surendra Kumar; Kumar, Dinesh

    2014-10-01

    Oxidative injury is markedly responsible for wound complications in diabetes mellitus. The biological actions of bilirubin may be relevant to prevent oxidant-mediated cell death, as bilirubin application at a low concentration scavenges reactive oxygen species. Hence, we hypothesized that topical bilirubin application might improve wound healing in diabetic rats. Diabetes was induced in adult male Wistar rats, which were divided into two groups, i.e., diabetic control and diabetic treated. Non-diabetic healthy rats were also taken as healthy control group. Wound area was measured on days 3, 7, 14, and 19 post-wounding. The levels of malondialdehyde (MDA) and reduced glutathione (GSH) and the activities of glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) were estimated in the granulation tissue. There was a significant increase in percent wound closure in healthy control and diabetic treated rats on days 7, 14, and 19, as compared to diabetic control rats on days 7, 14, and 19. There was significant decrease in MDA levels on days 7, 14, and 19 in diabetic treated rats, as compared to diabetic control rats. Levels of GSH were significantly increased on days 3, 7, 14, and 19 in diabetic treated rats, as compared to diabetic control rats. GPx, SOD, and CAT activities were significantly higher on days 3, 7, and 14 in diabetic treated rats, as compared to diabetic control rats. The findings indicate that bilirubin is effective in reducing the oxidant status in wounds of diabetic rats which might have accelerated wound healing in these rats.

  10. The preventive effect of lotus seedpod procyanidins on cognitive impairment and oxidative damage induced by extremely low frequency electromagnetic field exposure.

    Science.gov (United States)

    Duan, Yuqing; Wang, Zhigao; Zhang, Haihui; He, Yuanqing; Lu, Rongzhu; Zhang, Rui; Sun, Guibo; Sun, Xiaobo

    2013-08-01

    The present study investigated the effects of lotus seedpod procyanidins (LSPCs) administered by oral gavage on the cognitive deficits and oxidative damage of mice at extremely low frequency electromagnetic field (ELF-EMF) exposure (50 Hz, 8 mT, 28 days). The results showed that 90 mg kg⁻¹ LSPCs treatment significantly increased body weight compared with the ELF-EMF group at ELF-EMF exposure and effectively maintained liver index, thymus index, kidney index and spleen index close to normal. A water maze test indicated that learning and memory abilities of the ELF-EMF group deteriorated significantly with ELF-EMF exposure when compared with the control group, but the ELF-EMF + LSPCs90 group had remarkably improved learning and memory abilities compared with the ELF-EMF group. Malondialdehyde (MDA), reactive oxygen species (ROS), nitric oxide (NO) and nitric oxide synthase (NOS) mostly exhibited significant increases, while the activities of glutathione peroxidase (GPx), catalase (CAT) and superoxide dismutase (SOD) decreased significantly under ELF-EMF exposure in the ELF-EMF group. LSPCs (especially 60, 90 mg kg⁻¹) administration decreased MDA, ROS, NO content and lowered NOS activity in LSPCs treatment groups. Furthermore, LSPCs (60, 90 mg kg⁻¹) treatment significantly augmented GPx, CAT, SOD activity in the hippocampus and serum. Pathological observation showed that number of pyramidal cells of the CA1 and CA3 regions of the hippocampus of the LSPCs treatment groups was significantly greater than the ELF-EMF group. All the data suggested that the LSPCs can effectively prevent learning and memory damage and oxidative damage caused by the ELF-EMF, most likely through the ability of LSPCs to scavenge oxygen free radicals and to stimulate antioxidant enzyme activity.

  11. Ternary complexes of albumin-Mn(II)-bilirubin and Electron Spin Resonance studies of gallstones

    CERN Document Server

    Chikvaidze, E N; Kirikashvili, I N; Mamniashvili, G I

    2009-01-01

    The stability of albumin-bilirubin complex was investigated depending on pH of solution. It was shown that the stability of complex increases in presence of Mn(II) ions. It was also investigated the paramagnetic composition of gallstones by the electron spin resonance (ESR) method. It turned out that all investigated gallstones contain a free bilirubin radical-the stable product of its radical oxidation. Accordingly the paramagnetic composition gallstones could be divided on three main types: cholesterol, brown pigment and black pigment stones. ESR spectra of cholesterol stones is singlet with g=2.003 and splitting between components 1.0 mT. At the same time the brown gallstones, besides aforementioned signal contain the ESR spectrum which is characteristics for Mn(II) ion complexes with inorganic compounds and, finally, in the black pigment stones it was found out Fe(III) and Cu(II) complexes with organic compounds and a singlet of bilirubin free radical. It is supposed that crystallization centers of gallst...

  12. Impairment of Hepatic and Renal Functions by 2,5-Hexanedione Is Accompanied by Oxidative Stress in Rats

    Directory of Open Access Journals (Sweden)

    Isaac A. Adedara

    2014-01-01

    Full Text Available 2,5-Hexanedione (2,5-HD is the toxic metabolite of n-hexane which is widely used as solvent in numerous industries. The present study elucidated the precise mechanism of 2,5-HD in hepatorenal toxicity by determining the involvement of oxidative stress in rats. Adult male Wistar rats were exposed to 0, 0.25, 0.5, and 1% 2,5-HD in drinking water for 21 days. Exposure to 2,5-HD caused liver and kidney atrophy evidenced by significant elevation in serum aminotransferases, alkaline phosphatase, albumin, bilirubin, urea, creatinine, and electrolytes levels compared with control. The marked dose-dependent increase in total cholesterol (TC, triglyceride (TG, and low-density lipoprotein (LDL was accompanied with significant decrease in high-density lipoprotein (HDL levels in 2,5-HD-exposed animals when compared with the control. Administration of 2,5-HD significantly diminished glutathione (GSH level but increased the activities of superoxide dismutase (SOD, catalase, glutathione peroxidase (GPx, and glutathione-S-transferase (GST concomitantly with marked elevation in hydrogen peroxide (H2O2 and malondialdehyde (MDA levels in liver and kidney of the treated groups compared with control. These findings suggest that undue exposure to 2,5-HD at environmentally relevant levels may impair liver and kidney functions through induction of oxidative stress.

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

    Science.gov (United States)

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

    2016-01-01

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

  14. Usefulness of serum bilirubin levels as a biomarker for long-term clinical outcomes after percutaneous coronary intervention.

    Science.gov (United States)

    Kim, Hyun-Wook; Choi, Dong-Hyun; Lim, Leejin; Lee, Young-Min; Kang, Joon Tae; Chae, Seung Seok; Ki, Young-Jae; Song, Heesang; Koh, Young-Youp

    2015-11-01

    The aim of this study was to evaluate the prognostic value of serum total bilirubin on the development of adverse outcomes after percutaneous coronary intervention (PCI) besides high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-B type natriuretic peptide (NT-proBNP). Serum total bilirubin, hs-cTnT, and NT-proBNP were analyzed in 372 patients who underwent PCI. The primary endpoint was cardiac death. There were 21 events of cardiac death during a mean of 25.8 months of follow-up. When the serum total bilirubin cut-off level (median value) was set to 0.58 mg/dL using the receiver operating characteristic curve, the sensitivity was 95.2 % and the specificity was 51.0 % for differentiating between the group with cardiac death and the group without cardiac death. Kaplan-Meier analysis revealed that the lower serum total bilirubin group (bilirubin group (≥0.58 mg/dL) (10.4 vs. 0.6 %, log-rank: P = 0.0001). In conclusion, low serum total bilirubin is a predictive marker for cardiac death after PCI.

  15. Does corticosteroid treatment cause prolonged recovery and increased total bilirubin level in severe ADAMTS-13-deficient TTP patient?

    Science.gov (United States)

    Sayiner, Zeynel Abidin; Acik, Didar Yanardag; Yilmaz, Mehmet; Subari, Salih; Mete, Ayse Ozlem; Dai, M Sinan

    2015-10-01

    A 41-year-old female patient complaining of fatigue, headache, mild confusion, and rush on her lower extremities was admitted to our emergency department. Laboratory tests revealed that he had anemia, thrombocytopenia, and increased levels of indirect bilirubin and lactic dehydrogenase (LDH) in blood tests. Direct and indirect Coombs tests were negative, and fragmented erythrocytes were observed in peripheral blood smears. The patient was diagnosed with thrombotic thrombocytopenic purpura (TTP). The best supportive care was provided. Therapeutic plasma exchange (TPE) and 1 mg/kg methylprednisolone treatments were administered. On the 10th day of treatment, LDH level and fragmented red blood cells in peripheral blood smear were decreased, but his direct and indirect bilirubin levels increased despite the fact that he was treated with 1 mg/kg methylprednisolone and TPE. The patient had severe ADAMTS-13 deficiency. After discontinued steroids treatment, his bilirubin level normalized within 4 days. On the 4th day after bilirubin level normalized, vincristine treatment was administered. TPE was also continued. There was no consensus about the optimal schedule for discontinuing plasmapheresis therapy, and also we observed total bilirubin level improvement with discontinued corticosteroid treatment. In this case, corticosteroid treatment was linked with the increase of total bilirubin level in severe ADAMTS-13-deficient TTP patient.

  16. High serum total bilirubin as a protective factor against hip bone loss in healthy middle-aged men.

    Science.gov (United States)

    Kim, Beom-Jun; Koh, Jung-Min; Ahn, Seong Hee; Lee, Seung Hun; Kim, Eun Hee; Bae, Sung Jin; Kim, Hong-Kyu; Choe, Jae Won; Kim, Ghi Su

    2013-06-01

    Bilirubin is known to have a physiologic role as an antioxidant that efficiently scavenges peroxyl radicals and suppresses oxidation, and oxidative stress has detrimental effects on bone metabolism. In the present study, we performed a 3-year longitudinal study of healthy middle-aged men, investigating the association between serum total bilirubin concentrations and annualized changes in bone mineral density (BMD). The study enrolled a total of 917 Korean men aged 40 years or older who had undergone comprehensive routine health examinations with an average follow-up interval of 3 years. BMD at proximal femur sites was measured with dual-energy X-ray absorptiometry using the same equipment at baseline and follow-up. The overall mean annualized rates of bone loss at the total femur, femoral neck, and trochanter were -0.25 %/year, -0.34 %/year, and -0.44 %/year, respectively. After adjustment for potential confounders, the rates of bone loss at all proximal femur sites were significantly attenuated in a dose-response fashion across increasing bilirubin concentrations (P = 0.006-0.046). Moreover, compared to subjects in the lowest bilirubin quartile category, those in the highest bilirubin quartile category showed significantly less bone loss at all proximal femur sites after adjustment for confounding factors (P = 0.010-0.048). This study provides the first clinical evidence that serum total bilirubin could be a protective marker against future bone loss, especially in subjects without liver diseases.

  17. Prolonged exposure of cortical neurons to oligomeric amyloid-β impairs NMDA receptor function via NADPH oxidase-mediated ROS production: protective effect of green tea (–-epigallocatechin-3-gallate

    Directory of Open Access Journals (Sweden)

    Grace Y Sun

    2011-02-01

    Full Text Available Excessive production of Aβ (amyloid β-peptide has been shown to play an important role in the pathogenesis of AD (Alzheimer's disease. Although not yet well understood, aggregation of Aβ is known to cause toxicity to neurons. Our recent study demonstrated the ability for oligomeric Aβ to stimulate the production of ROS (reactive oxygen species in neurons through an NMDA (N-methyl-d-aspartate-dependent pathway. However, whether prolonged exposure of neurons to aggregated Aβ is associated with impairment of NMDA receptor function has not been extensively investigated. In the present study, we show that prolonged exposure of primary cortical neurons to Aβ oligomers caused mitochondrial dysfunction, an attenuation of NMDA receptor-mediated Ca2+ influx and inhibition of NMDA-induced AA (arachidonic acid release. Mitochondrial dysfunction and the decrease in NMDA receptor activity due to oligomeric Aβ are associated with an increase in ROS production. Gp91ds-tat, a specific peptide inhibitor of NADPH oxidase, and Mn(III-tetrakis(4-benzoic acid-porphyrin chloride, an ROS scavenger, effectively abrogated Aβ-induced ROS production. Furthermore, Aβ-induced mitochondrial dysfunction, impairment of NMDA Ca2+ influx and ROS production were prevented by pre-treatment of neurons with EGCG [(−-epigallocatechin-3-gallate], a major polyphenolic component of green tea. Taken together, these results support a role for NADPH oxidase-mediated ROS production in the cytotoxic effects of Aβ, and demonstrate the therapeutic potential of EGCG and other dietary polyphenols in delaying onset or retarding the progression of AD.

  18. Visual Impairment

    Science.gov (United States)

    ... What Causes Visual Impairment? People rarely lose their eyesight during their teen years. When they do, it's ... inflammation in the eye. It's often found in poor rural countries that have overcrowded living conditions and ...

  19. Exposure of E. coli to DNA-methylating agents impairs biofilm formation and invasion of eukaryotic cells via down regulation of the N-acetylneuraminate lyase NanA

    Directory of Open Access Journals (Sweden)

    Pamela eDi Pasquale

    2016-02-01

    Full Text Available DNA methylation damage can be induced by endogenous and exogenous chemical agents, which has led every living organism to develop suitable response strategies. We investigated protein expression profiles of Escherichia coli upon exposure to the alkylating agent methyl-methane sulfonate (MMS by differential proteomics. Quantitative proteomic data showed a massive downregulation of enzymes belonging to the glycolytic pathway and fatty acids degradation, strongly suggesting a decrease of energy production. A strong reduction in the expression of the N-acetylneuraminate lyases (NanA involved in the sialic acid metabolism was also observed. Using a null NanA mutant and DANA, a substrate analogue acting as competitive inhibitor, we demonstrated that down regulation of NanA affects biofilm formation and adhesion properties of E. coli MV1161. Exposure to alkylating agents also decreased biofilm formation and bacterial adhesion to Caco-2 eukaryotic cell line by the adherent invasive E. coli (AIEC strain LF82. Our data showed that methylation stress impairs E. coli adhesion properties and suggest a possible role of NanA in biofilm formation and bacteria host interactions.

  20. Exposure of E. coli to DNA-Methylating Agents Impairs Biofilm Formation and Invasion of Eukaryotic Cells via Down Regulation of the N-Acetylneuraminate Lyase NanA.

    Science.gov (United States)

    Di Pasquale, Pamela; Caterino, Marianna; Di Somma, Angela; Squillace, Marta; Rossi, Elio; Landini, Paolo; Iebba, Valerio; Schippa, Serena; Papa, Rosanna; Selan, Laura; Artini, Marco; Palamara, Anna Teresa; Palamara, Annateresa; Duilio, Angela

    2016-01-01

    DNA methylation damage can be induced by endogenous and exogenous chemical agents, which has led every living organism to develop suitable response strategies. We investigated protein expression profiles of Escherichia coli upon exposure to the alkylating agent methyl-methane sulfonate (MMS) by differential proteomics. Quantitative proteomic data showed a massive downregulation of enzymes belonging to the glycolytic pathway and fatty acids degradation, strongly suggesting a decrease of energy production. A strong reduction in the expression of the N-acetylneuraminate lyases (NanA) involved in the sialic acid metabolism was also observed. Using a null NanA mutant and DANA, a substrate analog acting as competitive inhibitor, we demonstrated that down regulation of NanA affects biofilm formation and adhesion properties of E. coli MV1161. Exposure to alkylating agents also decreased biofilm formation and bacterial adhesion to Caco-2 eukaryotic cell line by the adherent invasive E. coli (AIEC) strain LF82. Our data showed that methylation stress impairs E. coli adhesion properties and suggest a possible role of NanA in biofilm formation and bacteria host interactions.

  1. Exposure of E. coli to DNA-Methylating Agents Impairs Biofilm Formation and Invasion of Eukaryotic Cells via Down Regulation of the N-Acetylneuraminate Lyase NanA

    Science.gov (United States)

    Di Pasquale, Pamela; Caterino, Marianna; Di Somma, Angela; Squillace, Marta; Rossi, Elio; Landini, Paolo; Iebba, Valerio; Schippa, Serena; Papa, Rosanna; Selan, Laura; Artini, Marco; Palamara, Anna Teresa; Duilio, Angela

    2016-01-01

    DNA methylation damage can be induced by endogenous and exogenous chemical agents, which has led every living organism to develop suitable response strategies. We investigated protein expression profiles of Escherichia coli upon exposure to the alkylating agent methyl-methane sulfonate (MMS) by differential proteomics. Quantitative proteomic data showed a massive downregulation of enzymes belonging to the glycolytic pathway and fatty acids degradation, strongly suggesting a decrease of energy production. A strong reduction in the expression of the N-acetylneuraminate lyases (NanA) involved in the sialic acid metabolism was also observed. Using a null NanA mutant and DANA, a substrate analog acting as competitive inhibitor, we demonstrated that down regulation of NanA affects biofilm formation and adhesion properties of E. coli MV1161. Exposure to alkylating agents also decreased biofilm formation and bacterial adhesion to Caco-2 eukaryotic cell line by the adherent invasive E. coli (AIEC) strain LF82. Our data showed that methylation stress impairs E. coli adhesion properties and suggest a possible role of NanA in biofilm formation and bacteria host interactions. PMID:26904018

  2. Caffeine exposure during rat brain development causes memory impairment in a sex selective manner that is offset by caffeine consumption throughout life.

    Science.gov (United States)

    Ardais, Ana Paula; Rocha, Andréia S; Borges, Maurício Felisberto; Fioreze, Gabriela T; Sallaberry, Cássia; Mioranzza, Sabrina; Nunes, Fernanda; Pagnussat, Natália; Botton, Paulo Henrique S; Cunha, Rodrigo A; Porciúncula, Lisiane de Oliveira

    2016-04-15

    Caffeine is the psychostimulant most consumed worldwide. In moderate doses, it affords a beneficial effect in adults and upon aging, but has a deleterious effect during brain development. We now tested if caffeine consumption by rats (0.1, 0.3, 1.0 g/L in the drinking water, only during active cycle and weekdays) during adulthood could revert the potentially negative effects of caffeine during early life. Thus, we compared caffeine intake starting 15 days before mating and lasting either up to weaning (development) or up to adulthood, on behavior and synaptic proteins in male and female rats. Recognition memory was impaired only in female rats receiving caffeine (0.3 and 1.0 g/L) during development, coincident with increased proBDNF and unchanged BDNF levels in the hippocampus. Caffeine in both treatment regimens caused hyperlocomotion only in male rats, whereas anxiety-related behavior was attenuated in both sexes by caffeine (1.0 g/L) throughout life. Both caffeine treatment regimens decreased GFAP (as an astrocyte marker) and SNAP-25 (as a nerve terminals marker) in the hippocampus from male rats. TrkB receptor was decreased in the hippocampus from both sexes and treatment regimens. These findings revealed that caffeine intake during a specific time window of brain development promotes sex-dependent behavioral outcomes related to modification in BDNF signaling. Furthermore, caffeine throughout life can overcome the deleterious effects of caffeine on recognition memory during brain development in female rats.

  3. Inorganic mercury accumulation in brain following waterborne exposure elicits a deficit on the number of brain cells and impairs swimming behavior in fish (white seabream-Diplodus sargus).

    Science.gov (United States)

    Pereira, Patrícia; Puga, Sónia; Cardoso, Vera; Pinto-Ribeiro, Filipa; Raimundo, Joana; Barata, Marisa; Pousão-Ferreira, Pedro; Pacheco, Mário; Almeida, Armando

    2016-01-01

    The current study contributes to fill the knowledge gap on the neurotoxicity of inorganic mercury (iHg) in fish through the implementation of a combined evaluation of brain morphometric alterations (volume and total number of neurons plus glial cells in specific regions of the brain) and swimming behavior (endpoints related with the motor activity and mood/anxiety-like status). White seabream (Diplodus sargus) was exposed to realistic levels of iHg in water (2μgL(-1)) during 7 (E7) and 14 days (E14). After that, fish were allowed to recover for 28 days (PE28) in order to evaluate brain regeneration and reversibility of behavioral syndromes. A significant reduction in the number of cells in hypothalamus, optic tectum and cerebellum was found at E7, accompanied by relevant changes on swimming behavior. Moreover, the decrease in the number of neurons and glia in the molecular layer of the cerebellum was followed by a contraction of its volume. This is the first time that a deficit on the number of cells is reported in fish brain after iHg exposure. Interestingly, a recovery of hypothalamus and cerebellum occurred at E14, as evidenced by the identical number of cells found in exposed and control fish, and volume of cerebellum, which might be associated with an adaptive phenomenon. After 28 days post-exposure, the optic tectum continued to show a decrease in the number of cells, pointing out a higher vulnerability of this region. These morphometric alterations coincided with numerous changes on swimming behavior, related both with fish motor function and mood/anxiety-like status. Overall, current data pointed out the iHg potential to induce brain morphometric alterations, emphasizing a long-lasting neurobehavioral hazard.

  4. Age-dependent impairment of IgG responses to glycosylphosphatidylinositol with equal exposure to Plasmodium falciparum among Javanese migrants to Papua, Indonesia.

    Science.gov (United States)

    Hudson Keenihan, Sarah N; Ratiwayanto, Sutanti; Soebianto, Saraswati; Krisin; Marwoto, Harijani; Krishnegowda, Gowdahalli; Gowda, D Channe; Bangs, Michael J; Fryauff, David J; Richie, Thomas L; Kumar, Sanjai; Baird, J Kevin

    2003-07-01

    Immune responses directed at glycosylphosphatidylinositol (GPI) anchors of Plasmodium falciparum may offer protection against symptomatic malaria. To independently explore the effect of age on generation of the anti-GPI IgG response, we measured serum anti-GPI IgGs in a longitudinal cohort of migrant Javanese children (6-12 years old) and adults (> or = 20 years old) with equivalent numbers of exposures to P. falciparum in Papua, Indonesia. While the peak response in adults was achieved after a single infection, comparable responses in children required > or = 3-4 infections. Significantly fewer children (16%) than adults (41%) showed a high (optical density > 0.44) anti-GPI IgG response (odds ratio [OR] = 3.8, 95% confidence interval [CI] = 2.3-6.3, P < 0.0001), and adults were more likely to show a persistently high response (OR = 5.5, 95% CI = 1.0-56.8, P = 0.03). However, the minority of children showing a strong response were significantly less likely to experience symptoms with subsequent parasitemia compared with those with a weak response (OR = 4.0, 95% CI = 1.1-13.8, P = 0.02). This effect was not seen among high- and low-responding adults (OR = 1.2, 95% CI = 0.5-2.8, P = 0.60). Host age, independent of cumulative exposure, apparently represents a key determinant of the quantitative and qualitative nature of the IgG response to P. falciparum GPI.

  5. Dietary early-life exposure to contaminated eels does not impair spatial cognitive performances in adult offspring mice as assessed in the Y-maze and the Morris water maze.

    Science.gov (United States)

    Dridi, Imen; Leroy, Delphine; Guignard, Cédric; Scholl, Georges; Bohn, Torsten; Landoulsi, Ahmed; Thomé, Jean-Pierre; Eppe, Gauthier; Soulimani, Rachid; Bouayed, Jaouad

    2014-12-01

    Many environmental contaminants are introduced via the diet and may act as neurotoxins and endocrine disrupters, especially influencing growing organisms in early life. The purpose of this study was to examine whether dietary exposure of dams to fish naturally contaminated with xenobiotics, especially with polychlorinated biphenyls (PCBs) and heavy metals (e.g., mercury and lead), resulted in cognitive function deficits in adult offspring mice. Daily, four groups of dams (n = 10/group) ingested standard diet plus paste with/without eels, during gestation and lactation, from gestational day (GD) six until post natal day (PND) 21 (weaning). Dams orally ingested a standardized amount of eel (0.8 mg kg(-1) d(-1)) containing the six non-dioxin-like (NDL) PCBs (Σ6 NDL-PCBs: 28, 52, 101, 138, 153, and 180) at 0, 85, 216, and 400 ng kg(-1) d(-1). Results showed that early-life exposure to contaminated eels did not (compared to non-exposed controls) impair immediate working memory in the Y-maze in the offspring assessed at PND 38. Furthermore, it did not significantly impact spatial learning and retention memory as measured in the Morris water maze in adult offspring mice (PND 120-123). Our results suggest that perinatal exposure to contaminated eels does not affect spatial cognitive performances, as assessed by the Y-maze and Morris water maze at adult age. Adverse effects of xenobiotics reported earlier might be camouflaged by beneficial eel constituents, such as n-3 fatty acids. However, additional studies are needed to differentiate between potential positive and negative effects following consumption of food items both rich in nutrients and contaminants.

  6. Chronic exposure to chlorpyrifos triggered body weight increase and memory impairment depending on human apoE polymorphisms in a targeted replacement mouse model.

    Science.gov (United States)

    Peris-Sampedro, Fiona; Basaure, Pia; Reverte, Ingrid; Cabré, Maria; Domingo, José L; Colomina, Maria Teresa

    2015-05-15

    Despite restrictions on their use, humans are still constantly exposed to organophosphates (OPs). A huge number of studies have ratified the neurotoxic effects of chlorpyrifos (CPF) and suggested its association with neurodegenerative diseases, but data are still scarce. Human apolipoprotein E (apoE) plays an important role in lipid transport and distribution. In humans, the apoE4 isoform has been linked to an increased risk of Alzheimer's disease (AD). ApoE3 is the most prevalent isoform worldwide, and has been often established as the healthful one. The current study, performed in targeted replacement (TR) adult male mice, aimed to inquire whether genetic variations of the human apoE respond differently to a chronic dietary challenge with CPF. At four/five months of age, mice carrying apoE2, apoE3 or apoE4 were pair-fed a diet supplemented with CPF at 0 or 2mg/kg body weight/day for 13weeks. Cholinergic signs were monitored daily and body weight changes weekly. In the last week of treatment, learning and memory were assessed in a Barnes maze task. Dietary CPF challenge increased body weight only in apoE3 mice. Differences in the acquisition and retention of the Barnes maze were attributed to apoE genetic differences. Our results showed that apoE4 mice performed worse than apoE2 and apoE3 carriers in the acquisition period of the spatial task, and that apoE2 mice had poorer retention than the other two genotypes. On the other hand, CPF increased the search velocity of apoE2 subjects during the acquisition period. Retention was impaired only in CPF-exposed apoE3 mice. These results underline that gene×environment interactions need to be taken into account in epidemiological studies. Given that apoE3, the most common polymorphism in humans, has proved to be the most sensitive to CPF, the potential implications for human health merit serious thought.

  7. Bilirubin - blood

    Science.gov (United States)

    ... Gastroenterology. In: Rennie JM, ed. Rennie and Robsertson's Textbook of Neonatology. 5th ed. Philadelphia, PA: Elsevier; 2012:chap 29. Pratt DS. Liver chemistry and function tests. In: Feldman M, Friedman LS, ...

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

    Science.gov (United States)

    Rücker, Hannelore; Amslinger, Sabine

    2015-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-01-01

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

  10. 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.

  11. Abbreviated exposure to hypoxia is sufficient to induce CNS dysmyelination, modulate spinal motor neuron composition, and impair motor development in neonatal mice.

    Science.gov (United States)

    Watzlawik, Jens O; Kahoud, Robert J; O'Toole, Ryan J; White, Katherine A M; Ogden, Alyssa R; Painter, Meghan M; Wootla, Bharath; Papke, Louisa M; Denic, Aleksandar; Weimer, Jill M; Carey, William A; Rodriguez, Moses

    2015-01-01

    Neonatal white matter injury (nWMI) is an increasingly common cause of cerebral palsy that results predominantly from hypoxic injury to progenitor cells including those of the oligodendrocyte lineage. Existing mouse models of nWMI utilize prolonged periods of hypoxia during the neonatal period, require complex cross-fostering and exhibit poor growth and high mortality rates. Abnormal CNS myelin composition serves as the major explanation for persistent neuro-motor deficits. Here we developed a simplified model of nWMI with low mortality rates and improved growth without cross-fostering. Neonatal mice are exposed to low oxygen from postnatal day (P) 3 to P7, which roughly corresponds to the period of human brain development between gestational weeks 32 and 36. CNS hypomyelination is detectable for 2-3 weeks post injury and strongly correlates with levels of body and brain weight loss. Immediately following hypoxia treatment, cell death was evident in multiple brain regions, most notably in superficial and deep cortical layers as well as the subventricular zone progenitor compartment. PDGFαR, Nkx2.2, and Olig2 positive oligodendrocyte progenitor cell were significantly reduced until postnatal day 27. In addition to CNS dysmyelination we identified a novel pathological marker for adult hypoxic animals that strongly correlates with life-long neuro-motor deficits. Mice reared under hypoxia reveal an abnormal spinal neuron composition with increased small and medium diameter axons and decreased large diameter axons in thoracic lateral and anterior funiculi. Differences were particularly pronounced in white matter motor tracts left and right of the anterior median fissure. Our findings suggest that 4 days of exposure to hypoxia are sufficient to induce experimental nWMI in CD1 mice, thus providing a model to test new therapeutics. Pathological hallmarks of this model include early cell death, decreased OPCs and hypomyelination in early postnatal life, followed by

  12. Morphological and antioxidant impairments in the spinal cord of male offspring rats following exposure to a continuous 900MHz electromagnetic field during early and mid-adolescence.

    Science.gov (United States)

    İkinci, Ayşe; Mercantepe, Tolga; Unal, Deniz; Erol, Hüseyin Serkan; Şahin, Arzu; Aslan, Ali; Baş, Orhan; Erdem, Havva; Sönmez, Osman Fikret; Kaya, Haydar; Odacı, Ersan

    2016-09-01

    The effects of devices emitting electromagnetic field (EMF) on human health have become the subject of intense research among scientists due to the rapid increase in their use. Children and adolescents are particularly attracted to the use of devices emitting EMF, such as mobile phones. The aim of this study was therefore to investigate changes in the spinal cords of male rat pups exposed to the effect of 900MHz EMF. The study began with 24 Sprague-Dawley male rats aged 3 weeks. Three groups containing equal numbers of rats were established-control group (CG), sham group (SG) and EMF group (EMFG). EMFG rats were placed inside an EMF cage every day between postnatal days (PD) 21 and 46 and exposed to the effect of 900MHz EMF for 1h. SG rats were kept in the EMF cage for 1h without being exposed to the effect of EMF. At the end of the study, the spinal cords in the upper thoracic region of all rats were removed. Tissues were collected for biochemistry, light microscopy (LM) and transmission electron microscopic (TEM) examination. Biochemistry results revealed significantly increased malondialdehyde and glutathione levels in EMFG compared to CG and SG, while SG and EMFG catalase and superoxide dismutase levels were significantly higher than those in CG. In EMFG, LM revealed atrophy in the spinal cord, vacuolization, myelin thickening and irregularities in the perikarya. TEM revealed marked loss of myelin sheath integrity and invagination into the axon and broad vacuoles in axoplasm. The study results show that biochemical alterations and pathological changes may occur in the spinal cords of male rats following exposure to 900MHz EMF for 1h a day on PD 21-46.

  13. All Vision Impairment

    Science.gov (United States)

    ... Home > Statistics and Data > All Vision Impairment All Vision Impairment Vision Impairment Defined Vision impairment is defined as the ... Ethnicity 2010 U.S. Age-Specific Prevalence Rates for Vision Impairment by Age and Race/Ethnicity Table for ...

  14. Chronic exposure to MDMA (ecstasyinduces DNA damage, impairs functional antioxidant cellular defenses, enhances the lipid peroxidation process and alters testes histopathology in male rat

    Directory of Open Access Journals (Sweden)

    Nadia Gamal Zaki, ** Laila Abdel Kawy

    2013-04-01

    Full Text Available Background : 3,4-Methylenedioxymethamphetamine (MDMA or "ecstasy" is consumed mainly by young population. For this reason, it is especially relevant to take into consideration the effects on the reproductive system. The influence of MDMA on the fertility and reproduction of the male rat was assessed in this study. Material and methods: MDMA was administered orally at 0 mg/kg (control, 10 and 30 mg/kg to male rats for 15,30,45 consecutive days followed by 15 days withdrawal. Hormonal, biochemical, histological and testicular were evaluated in the rats. The present study aimed to investigate if daily oral administration of ecstasy at low doses(10mg for 45 days has any deleterious effects on reproductive functions of male rats. Animals were randomly divided into four groups of ten rats each, assigned as control rats, or(0mg ecstasy, rats treated with 10mg ecstasy for, (15,30,45 days, rats treated with 30mg/kg body weight ecstasy for(,15,30,45days by oral gavage. The third group(45 days was followed by 15 withdrawal period(W15. Results: The activities of superoxide dismutase, catalase, glutathione reductase and glutathione peroxidase in testicular homogenate were decreased while the levels of lipid peroxidation increased significantly in the treated rats as compared with the corresponding group of control animals. In group 30mg, only, arachidonic acid was significantly elevated in the testicular homogenate while linoleic acid was decresed when compared to control. Testis DNA fragmentation was observed in 30mg group, but not 10.mg. It is concluded that low doses of ecstasy exposure(10 mg/Kg had moderate detrimental effects on reproductive organ system and more severe effects are likely to be observed at higher dose levels. These results indicate that ecstasy is directly toxic to primary Leydig cells, and that the decreased percentage of normal cells and the increased level of DNA damage in ecstasy -exposed Leydig cells may be responsible for

  15. 胆红素脑病与胆红素/血浆白蛋白比值关系探讨%The study of the relationship between bilirubin encephalopathy and bilirubin/albumin

    Institute of Scientific and Technical Information of China (English)

    刘新晖; 李贵南; 胡月圆; 张慧; 周勇

    2011-01-01

    目的 探讨胆红素脑病与血清胆红素/血浆白蛋白比值( B/A)的关系.方法 对2008年11月至2009年10月本院住院的高胆红素血症患儿进行回顾性总结,分为胆红素脑病组(病例组)与非胆红素脑病组(对照组),对住院期间的血清胆红素高峰值、血浆白蛋白以及B/A等因素之间的关系进行统计学分析.结果 共收集到2253例高胆红素血症患儿,其中88例诊断胆红素脑病.病例组B/A为(1.59±0.47),对照组B/A为(0.80±0.28),差异有统计学意义(t=474.537,P=0.000).B/A比值为0~1.0、1.1 ~2.0、2.1 ~3.0时,胆红素脑病发生率分别为0.5%、12.9%、69.2%.结论 胆红素脑病的发生与B/A比值有关,B/A越高,发生胆红素脑病的危险性越大.%Objective The relationship between the bilirubin encephalopathy and bilirubin/ albumin (B/A) is discussed. Methods Cases with hyperbilirubinemia in hospital from Dec 2008 to Oct 2009, assigned into bilirubin encephalopathy group and control group, the relationship among bilirubin peak, albumin and B/A were analyzed retrospectively. Results Of the 2253 babies with hyperbilirubinemia, A total of 88 babies developed bilirubin encephalopathy. The B/A value in bilirubin encephalopathy group was 1. 59 ±0. 47, and control group was 0. 80 ±0. 28, with significant differences between two groups (t = 474. 537, P = 0. 000). The incidence of bilirubin encephalopathy at different levels of B/A was different; 0 - 1. 0, 0. 5% ; 1. 1 -2.0, 12. 9% ; 2. 1 - 3. 0, 69. 2% . Conclusion The incidence of bilirubin encephalopathy is significantly associated with the levels of B/A.

  16. Impaired cholecystokinin-induced gallbladder emptying incriminated in spontaneous "black" pigment gallstone formation in germfree Swiss Webster mice.

    Science.gov (United States)

    Woods, Stephanie E; Leonard, Monika R; Hayden, Joshua A; Brophy, Megan Brunjes; Bernert, Kara R; Lavoie, Brigitte; Muthupalani, Sureshkumar; Whary, Mark T; Mawe, Gary M; Nolan, Elizabeth M; Carey, Martin C; Fox, James G

    2015-02-15

    "Black" pigment gallstones form in sterile gallbladder bile in the presence of excess bilirubin conjugates ("hyperbilirubinbilia") from ineffective erythropoiesis, hemolysis, or induced enterohepatic cycling (EHC) of unconjugated bilirubin. Impaired gallbladder motility is a less well-studied risk factor. We evaluated the spontaneous occurrence of gallstones in adult germfree (GF) and conventionally housed specific pathogen-free (SPF) Swiss Webster (SW) mice. GF SW mice were more likely to have gallstones than SPF SW mice, with 75% and 23% prevalence, respectively. In GF SW mice, gallstones were observed predominately in heavier, older females. Gallbladders of GF SW mice were markedly enlarged, contained sterile black gallstones composed of calcium bilirubinate and cholecystokinin (CCK), gallbladders of fasted GF SW mice showed impaired emptying (females: 29%; males: 1% emptying), whereas SPF SW females and males emptied 89% and 53% of volume, respectively. Bilirubin secretion rates of GF SW mice were not greater than SPF SW mice, repudiating an induced EHC. Gallstones likely developed in GF SW mice because of gallbladder hypomotility, enabled by features of GF physiology, including decreased intestinal CCK concentration and delayed intestinal transit, as well as an apparent genetic predisposition of the SW stock. GF SW mice may provide a valuable model to study gallbladder stasis as a cause of black pigment gallstones.

  17. The association between indirect bilirubin levels and liver fibrosis due to chronic hepatitis C virus infection.

    Science.gov (United States)

    Cengiz, Mustafa; Yılmaz, Guldal; Ozenirler, Seren

    2014-08-01

    We proposed to evaluate the association between serum indirect bilirubin levels and liver fibrosis in patients with chronic hepatitis C (CHC) genotype 1b. Biopsy proven CHC genotype 1b patients' demographics, clinical and histopathological characteristics were evaluated. Logistic regression analysis was done to evaluate the clinical, laboratory and demographic features of the histologically proven liver fibrosis in CHC patients. A total of 112 biopsy proven CHC genotype 1b patients were enrolled into the study. Liver fibrosis scores were measured by using Ishak fibrosis scores and were divided into two groups; fibrosis scores ≤ 2 were categorized as mild fibrosis, 82 patients (73.2%), whereas fibrosis scores >2 were categorized as advanced fibrosis group, 30 patients (26.8%). Patients with advanced fibrosis had lower indirect bilirubin levels than the mild fibrosis group (0.28 ± 0.02 mg/dl vs. 0.44 ± 0.032 mg/dl, pbilirubin level was negatively correlated with advanced fibrosis scores (r=-0.416 and pbilirubin level was an independent predicting factor of advanced liver fibrosis (OR: 0.001, 95% CI: 0.0-0.005, pbilirubin levels and advanced liver fibrosis caused by CHC genotype 1b.

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

    Science.gov (United States)

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

    2014-11-01

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

  19. Effects of Calcium Ions on Thermodynamic Properties of Mixed Bilirubin/Cholesterol Monolayers

    Science.gov (United States)

    Wu, Qiong; Tang, Yu-feng; Li, Ye-min; Xie, An-jian; Shen, Yu-hua; Zhu, Jin-miao; Li, Chuan-hao

    2008-04-01

    The mixed monolayer behavior of bilirubin/cholesterol was studied through surface pressure-area (π-A) isotherms on aqueous solutions containing various concentrations of calcium ions. Based on the data of π-A isotherms, the mean area per molecule, collapse pressure, surface compressibility modulus, excess molecular areas, free energy of mixing, and excess free energy of mixing of the monolayers on different subphases were calculated. The results show an expansion in the structure of the mixed monolayer with Ca2+ in subphase, and non-ideal mixing of the components at the air/water interface is observed with positive deviation from the additivity rule in the excess molecular areas. The miscibility between the components is weakened with the increase of concentration of Ca2+ in subphase. The facts indicate the presence of coordination between Ca2+ and the two components. The mixed monolayer, in which the molar ratio of bilirubin to cholesterol is 3:2, is more stable from a thermodynamic point of view on pure water. But the stable 3:2 stoichiometry complex is destroyed with the increase of the concentration of Ca2+ in subphase. Otherwise, the mixed monolayers have more thermodynamic stability at lower surface pressure on Ca2+ subphase.

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

    Energy Technology Data Exchange (ETDEWEB)

    Nogala, Wojciech; Celebanska, Anna; Szot, Katarzyna [Institute of Physical Chemistry, Polish Academy of Sciences, Warsaw (Poland); Wittstock, Gunther, E-mail: gunther.wittstock@uni-oldenburg.d [Carl von Ossietzky University of Oldenburg, Faculty of Mathematics and Science, Center of Interface Science (CIS), Department of Pure and Applied Chemistry, D-26111 Oldenburg (Germany); Opallo, Marcin, E-mail: mopallo@ichf.edu.p [Institute of Physical Chemistry, Polish Academy of Sciences, Warsaw (Poland)

    2010-08-01

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

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

    Directory of Open Access Journals (Sweden)

    Minjong Lee

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

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

    Science.gov (United States)

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

    2015-12-01

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

  3. Effects of Calcium Ions on Thermodynamic Properties of Mixed Bilirubin/Cholesterol Monolayers

    Institute of Scientific and Technical Information of China (English)

    Qiong Wu; Yu-feng Tang; Ye-min Li; An-jian Xie; Yu-hua Shen; Jin-miao Zhu; Chuan-hao Li

    2008-01-01

    The mixed monolayer behavior of bilirubin/cholesterol was studied through surface pressure-area (π-A) isotherms on aqueous solutions containing various concentrations of calcium ions.Based on the data of π-A isotherms,the mean area per molecule,collapse pressure,surface compressibility modulus,excess molecular areas,free energy of mixing,and excess free energy of mixing of the monolayers on different subphases were calculated.The results show an expansion in the structure of the mixed monolayer with Ca2+ in subphase, and non-ideal mixing of the components at the air/water interface is observed with positive deviation from the additivity rule in the excess molecular areas.The miscibility between the components is weakened with the increase of concentration of Ca2+ in subphase.The facts indicate the presence of coordination between Ca2+ and the two components.The mixed monolayer,in which the molar ratio of bilirubin to cholesterol is 3:2,is more stable from a thermodynamic point of view on pure water.But the stable 3:2 stoichiometry complex is destroyed with the increase of the concentration of Ca2+ in subphase.Otherwise,the mixed monolayers have more thermodynamic stability at lower surface pressure on Ca2+ subphase.

  4. Amplifying the fluorescence of bilirubin enables the real-time detection of heme oxygenase activity.

    Science.gov (United States)

    Klemz, Roman; Mashreghi, Mir-Farzin; Spies, Claudia; Volk, Hans-Dieter; Kotsch, Katja

    2009-01-15

    Heme oxygenases (HO) are the rate-limiting enzymes in the degradation of heme to equimolar amounts of antioxidant bile pigments, the signaling molecule carbon monoxide, and ferric iron. The inducible form HO-1 confers protection on cells and tissues that mediates beneficial effects in many diseases. Consequently, measurement of the enzymatic activity is vital in the investigation of the regulatory role of HO. Here we report that the fluorescence characteristics of bilirubin in complex with serum albumin can be used for the real-time detection of HO activity in enzymatic kinetics measurements. We characterized the enzymatic activity of a truncated human HO-1 and measured the HO activity for various cell types and organs, in either the basal naive or the HO-1-induced state. The bilirubin-dependent increase in fluorescence over time monitored by this assay facilitates a very fast, sensitive, and reliable measurement of HO activity. Our approach offers the basis for a highly sensitive high-throughput screening, which provides, inter alia, the opportunity to discover new therapeutic HO-1-inducing agents.

  5. EFFECT OF BENZOIN RESIN ON THE SERUM BILIRUBIN LEVELS IN TEMPORARY JAUNDICE INDUCED BY PHENYLHYDRAZINE: A PRELIMINARY STUDY

    Directory of Open Access Journals (Sweden)

    RAJU.S, UMA MAHESHWARA RAO.V SREERAMULU REDDY.K, RAMYA.G, VASANTH KUMAR. G

    2013-10-01

    Full Text Available Bilirubin is the degradation product of heme, thebulk of which is derived from hemoglobin of senescenterythrocytes and hepatic hemoproteins. Bilirubin ispotentially toxic, but is normally rendered harmless bybinding to plasma albumin, and efficient hepatic clearance.Jaundice, (also known as icterus is a yellowishpigmentation of the skin, the conjunctival membranes overthe sclerae (whites of the eyes, and other mucousmembranes caused by hyperbilirubinemia (increased levelsof bilirubin in the blood. Complications of jaundiceinclude sepsis especially cholangitis, biliary cirrhosis,pancreatitis, coagulopathy, renal and liver failure.Treatment of rats with Phenylhydrazine 5 mg/ kg bodyweight for five days resulted in the development ofjaundice as BR level was found to be higher than 2 mg/dL.Bilirubin lowering potential of Benzoin ethyl alcoholextract was evaluated in temporarily jaundiced adultwistar rats. Treatment of these rats with Benzoin extractfor seven days reduced the BR level significantly to thenormal value. Whereas smaller dose (10mg/kg bodyweight resulted in the reduction in BR level from 2.51 ±0.02 to 0.90 ± 0.01 mg/dL, higher doses of 20 and 40mg/kg body weight were found to be more effective inreducing the bilirubin level from 2.54 ± 0.01 to 0.82 ±0.01 mg/dL and from 2.49±0.02 to 0.66±0.01 mg/dL,respectively. Therefore, Benzoin ethyl alcohol extract canbe used to reduce bilirubin concentration to a normal levelin jaundiced subjects.

  6. Lower carotid intima media thickness is predicted by higher serum bilirubin in both non-diabetic and Type 2 diabetic subjects

    NARCIS (Netherlands)

    Dullaart, Robin P. F.; Kappelle, Paul J.W.H.; de Vries, Rindert

    2012-01-01

    Background: Higher serum bilirubin levels may be implicated cardiovascular protection. It is unknown whether the impact of serum bilirubin on carotid artery intima media thickness (IMT), a marker of subclinical atherosclerosis, is different in diabetic subjects compared to non-diabetic subjects. We

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

    Science.gov (United States)

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

    2016-08-01

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

  8. Significance of total bilirubin/albumin in predicting bilirubin neurotoxicity%新生儿总胆红素与白蛋白比值对预测胆红素神经毒性的临床意义

    Institute of Scientific and Technical Information of China (English)

    陈清; 苏卫东; 瞿尔力; 黄育丹; 邓秀睿

    2011-01-01

    目的 探讨新生儿血清总胆红素/白蛋白在预测胆红素神经毒性方面的临床意义.方法 选择2007年5月至2010年8月住院治疗的高胆红素血症新生儿83例,检测其血清总胆红素和白蛋白等,并计算血清总胆红素/白蛋白,同时根据脑干听觉诱发电位(BAEP)的检测结果分为BAEP正常组和BAEP异常组,并对比观察.结果 BAEP异常组27例,BAEP正常组56例,BAEP 异常组的血清总胆红素、血清总胆红素/白蛋白均显著高于BAEP正常组[(356.50±59.23)μmol/L比(318.70±55.12)μmol/L、(5.02±0.49)×10-3比(4.56±0.43)×10-3],差异有统计学意义(P0.05).结论 血清总胆红素/白蛋白较血清总胆红素更能反映高胆红素血症新生儿血中游离胆红素的水平,可作为评估胆红素神经毒性危险因素的指标之一.%Objective To investigate the significance of total bilirubin/albumin in predicting bilirubin neurotoxicity.Methods Eighty-three cases with hyperbilirubinemia who treated from May 2007 to August 2010 were selected,the serum total bilirubin and albumin were detected and total bilirubin/albumin was calculated.According to brainstem auditory evoked potential(BAEP)results,the patients were divided into normal BAEP group and abnormal BAEP group and compared.Results There were 27 cases of abnormal BAEP group and 56 cases of normal BAEP group.Total bilirubin and total bilirubin/albumin in abnormal BAEP group were higher than those in normal BAEP group[(356.50±59.23)μmol/L vs.(318.70±55.12)μmol/L,(5.02±0.49)×10-3 vs.(4.56±0.43)×10-3],the differences were significant (P0.05).Conclusion Total bilirubin/albumin can reflect serum unconjugated bilirubin level of neonatus with hyperbilirubinemia better than total bilirubin,and it can can be taken as one index to evaluate the risk factors of bilirubin neurotoxicity.

  9. Subtle bilirubin-induced neurodevelopmental dysfunction (BIND) in the term and late preterm infant : Does it exist?

    NARCIS (Netherlands)

    Lunsing, Roelineke J.

    2014-01-01

    Subtle bilirubin-induced neurological dysfunction (BIND) is defined as disturbances in sensory and sensorimotor integration, central auditory processing, coordination, and muscle tone in the absence of the classical findings of kernicterus. This review is restricted to the (sensori)motor signs of BI

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

    NARCIS (Netherlands)

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

    2013-01-01

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

  11. [Postpartal serum bilirubin levels in the newborn after induction of labour with "prostaglandin cap" or oxytocin (author's transl)].

    Science.gov (United States)

    Grünberger, W; Coradello, H; Huber, J; Husslein, P

    1981-04-01

    In the course of a prospective study the development of Serum bilirubine levels was controlled in 90 neonates. In 30 cases labour had been induced by means of intravenous oxytocin infusion, in a further 30 cases by means of local peri-cervical prostaglandine E2 (PGE2)-application. The control group consisted of 30 children, with spontaneous onset of labour. Anamnesis, duration of gravidity, course of labour and method of delivery were the same in all groups; the neonates were all treated the same. The serum bilirubine was determined fotometrically with the Greiner Selective Analyzer GSA II on the 1st, 3rd and 5th post partum day and the results assessed by the multivariant analysis according to Newman-Keuls. No differences were found between the PGE2- and the control group, the bilirubine values of the oxytocin groups were significantly higher (p less than 0.001). Icteric neonates with serum bilirubine values of greater than 12 mg% were found more than double as often in the oxytocin group than in the PGE2- group (7:3). The results indicate, that for labour induction by pharmaceuticals, local application of PGE2 by means of a portio cap should be favored over intravenous oxytocin administration.

  12. The Research of Bilirubin Levels in Neonatal Cerebrospinal Fluid in the Diagnosis of Bilirubin Encephalopathy%新生儿脑脊液胆红素在胆红素脑病诊断中的研究

    Institute of Scientific and Technical Information of China (English)

    孙路璐; 金玉莲; 刘光辉; 张健; 郑洪

    2013-01-01

    Objective To investigate the value of concentration of bilirubin in cerebrospinal fluid for early diagnosis of neonatal bilirubin encephalopathy.Methods 34 cases with bilirubin encephalopathy and 37 cases with non-bilirubin encephalopathy as control group were chosen from February 2011 to October 2012.The concentrations of unconjugated bilirubin in cerebrospinal fluid and unconjugated bilirubin in serum of two groups were compared.According to the ROC curve,their critical value,sensitivity,specificity,positive predictive value and negative predictive value in the diagnosis of bilirubin encephalopathy were analyzed.Results The unconjugated bilirubin in cerebrospinal fluid in the bilirubin encephalopathy group (13.88 ± 5.03)μmol/L was significant higher than that in the control group (5.83 ± 4.30)μmol/L(P < 0.01),there was statistical significance in difference (P < 0.01).The area under curve of unconjugated bilirubin in cerebrospinal fluid(0.909) was larger than that of unconjugated bilirubin in serum(0.692),according to the ROC curve.When the critical value was 9.55 μmol/L,the sensitivity and specificity of unconjugated bilirubin in cerebrospinal fluid in the diagnosis of neonatal bilirubin encephalopathy were 86.7% and 93.9%,respectively.Conclusion Unconjugated bilirubin in cerebros-pinal fluid value was a good indicator for predicting bilirubin encephalopathy and it was helpful to provide information for rational clinical treatment of hyperbilirubinemia.%目的 探讨高胆红素血症新生儿脑脊液未结合胆红素水平对胆红素脑病的早期诊断价值.方法 以2011年2月-2012年10月入院的34例胆红素脑病患儿(病例组)和37例单纯高胆红素血症患儿(对照组)为研究对象,比较两组脑脊液及血清未结合胆红素水平,并绘制ROC曲线,计算脑脊液未结合胆红素及血清未结合胆红素水平在诊断胆红素脑病中的临界值、灵敏度、特异度、阳性预

  13. Prenatal Caffeine Exposure Impairs Pregnancy in Rats

    Directory of Open Access Journals (Sweden)

    Maryam Yadegari

    2016-12-01

    Full Text Available Background: In recent years, concerns have been raised about human reproductive disorders. Caffeine consumption is increasing by the world’s population and there is a relationship between caffeine intake and adverse reproductive outcomes. The aim of this study was to evaluate the effects of caffeine on implantation sites, number of live births, birth weight, crown-rump length (CRL and abnormality in pregnant rats. Materials and Methods: In this experimental study, 40 female albino rats (170-190 g were randomly divided into two experimental and two control groups (n=10/each group. In both experimental groups, animals received caffeine intraperitoneally (IP: 150 mg/kg/day on days 1-5 of pregnancy. In experimental group 1, treated animals were euthanized on day 7of pregnancy and the number of implantation sites was counted. In experimental group 2, treated animals maintained pregnant and after delivery, the number of live births, birth weight, CRL and abnormality of neonates were investigated. In control group, animals received IP injections of distilled water. Data were analyzed by independent t test. Results: Results showed that administration of caffeine significantly decreased the number of implantation sites, number of live births and CRL as compared with control group (P<0.05. There were no significant differences regarding birth weight and abnormality of neonate rats between experimental and control groups. Conclusion: These results suggest that caffeine caused anti-fertility effect and significantly decreased CRL in neonate rats.

  14. Effects of Bilirubin on Alveolar Macrophages in Rats with Emphysema and Expression of iNOS and NO in Them

    Institute of Scientific and Technical Information of China (English)

    李建强; 赵卉; 宋满景; 徐永健; 张珍祥

    2004-01-01

    To explore the effects of bilirubin on alveolar macrophages (AM) and expression of iNOS and NO in them in emphysema model, the rats were pretreated with bilirubin before exposed to smoke. AM were isolated from bronchoalveolar lavage fluid (BALF) and cultured. Pathological microscopic examination of AM and immunohistochemical analysis of iNOS were performed. Nitric oxide (NO) content in the samples was determined by nitrate reductase technique. The results showed both alveoli and alveolar septum appeared normal in size and shape in normal group. AM showed kidney-shaped nucleus and were rich in Golgi complexes and primary lysosomes in the cytoplasm. The inner membrane of mitochondrion was continuous. Most cristae of the mitochondria were intact. In model group, the alveoli were expanded, ruptured and bullaes were formed. Both the population and sizes of AM increased significantly. Secondary lysosomes were rich in the cytoplasm. Deformation and pyknosis of the nucleus, swelling of the mitochondrions and rupture of the inner mitochondrial membrane could also be seen. At high magnification, most of the mitochondrial cristae were broken, or completely lost at certain points. In bilirubin group, alveoli partly expanded and the population of AM also increased, with morphological changes being slighter than that in model group. Both NO contents and expression of iNOS in model group were higher than those in normal group (P<0.05). In bilirubin group the two indice were lower than those in model group (P<0.05). Our findings suggested that high expression of iNOS and high NO content in AM accelerate the development of emphysema associated with smoking in rats. Bilirubin may exert protective effects on AM and retards the development of emphysema in rats.

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

    LENUS (Irish Health Repository)

    Qualter, Yvonne M

    2012-01-31

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2015-01-01

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

  17. NAD+ Attenuates Bilirubin-Induced Hyperexcitation in the Ventral Cochlear Nucleus by Inhibiting Excitatory Neurotransmission and Neuronal Excitability

    Science.gov (United States)

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

    2017-01-01

    Nicotinamide adenine dinucleotide (NAD+) is an important molecule with extensive biological functions in various cellular processes, including protection against cell injuries. However, little is known regarding the roles of NAD+ in neuronal excitation and excitotoxicity associated with many neurodegenerative disorders and diseases. Using patch-clamp recordings, we studied its potential effects on principal neurons in the ventral cochlear nucleus (VCN), which is particularly vulnerable to bilirubin excitotoxicity. We found that NAD+ effectively decreased the size of evoked excitatory postsynaptic currents (eEPSCs), increased paired-pulse ratio (PPR) and reversed the effect of bilirubin on eEPSCs, implicating its inhibitory effects on the presynaptic release probability (Pr). Moreover, NAD+ not only decreased the basal frequency of miniature EPSCs (mEPSCs), but also reversed bilirubin-induced increases in the frequency of mEPSCs without affecting their amplitude under either condition. Furthermore, we found that NAD+ decreased the frequency of spontaneous firing of VCN neurons as well as bilirubin-induced increases in firing frequency. Whole-cell current-clamp recordings showed that NAD+ could directly decrease the intrinsic excitability of VCN neurons in the presence of synaptic blockers, suggesting NAD+ exerts its actions in both presynaptic and postsynaptic loci. Consistent with these observations, we found that the latency of the first postsynaptic spike triggered by high-frequency train stimulation of presynaptic afferents (i.e., the auditory nerve) was prolonged by NAD+. These results collectively indicate that NAD+ suppresses presynaptic transmitter release and postsynaptic excitability, jointly weakening excitatory neurotransmission. Our findings provide a basis for the exploration of NAD+ for the prevention and treatment of bilirubin encephalopathy and excitotoxicity associated with other neurological disorders. PMID:28217084

  18. Excessive bilirubin elevation in a patient with hereditary spherocytosis and intrahepatic cholestasis.

    Science.gov (United States)

    Wree, A; Canbay, A; Müller-Beissenhirtz, H; Dechêne, A; Gerken, G; Dührsen, U; Lammert, F; Nückel, H

    2011-08-01

    Hereditary spherocytosis is a common hemolytic anemia with an estimated incidence of 1 / 2500 births. It is caused by a molecular defect in one or more of the proteins of the red blood cell cytoskeleton. Mutations in the ABCB11 gene, encoding the bile salt export pump, can entail progressive familial intrahepatic cholestasis and benign recurred intrahepatic cholestasis. A 18 year old Turkish patient with hereditary spherocytosis was admitted to hospital with pruritus and severe jaundice. Ultrasound examination presented stones in gallbladder and bile duct. After endoscopic retrograde cholangiography with extraction of small bile duct stones abdominal pain resolved and liver enzymes normalized within a few days, but bilirubin and bile acids remained highly elevated. Liver biopsy revealed a severe canalicular cholestasis. Genetic analysis showed the compound heterozygous variants ABCB11 A 444V and 3084A > G. Treatment with ursodesoxycholic acid and intermittent therapy with prednisone reduced pruritus and jaundice with concomitant improvement of blood test. Here we report the first case of a patient with combined hereditary spherocytosis and compound heterozygous ABCB11 gene variants predisposing to intrahepatic cholestasis. Therefore, patients with hemolytic disorders should be investigated for bile acid transporter diseases in case of hyperbilirubinemia and severe cholestasis.

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

    Science.gov (United States)

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

    2016-11-01

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

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

    Science.gov (United States)

    Liu, Youxun; Huang, Juan; Zhang, Xiaoyu

    2009-12-01

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

  1. Bilirubin oxidation end products directly alter K+ channels important in the regulation of vascular tone.

    Science.gov (United States)

    Hou, Shangwei; Xu, Rong; Clark, Joseph F; Wurster, William L; Heinemann, Stefan H; Hoshi, Toshinori

    2011-01-01

    The exact etiology of delayed cerebral vasospasm following cerebral hemorrhage is not clear, but a family of compounds termed 'bilirubin oxidation end products (BOXes)' derived from heme has been implicated. As proper regulation of vascular smooth muscle tone involves large-conductance Ca(2+)- and voltage-dependent Slo1 K(+) (BK, maxiK, K(Ca)1.1) channels, we examined whether BOXes altered functional properties of the channel. Electrophysiological measurements of Slo1 channels heterologously expressed in a human cell line and of native mouse BK channels in isolated cerebral myocytes showed that BOXes markedly diminished open probability. Biophysically, BOXes specifically stabilized the conformations of the channel with its ion conduction gate closed. The results of chemical amino-acid modifications and molecular mutagenesis together suggest that two specific lysine residues in the structural element linking the transmembrane ion-permeation domain to the carboxyl cytosolic domain of the Slo1 channel are critical in determining the sensitivity of the channel to BOXes. Inhibition of Slo1 BK channels by BOXes may contribute to the development of delayed cerebral vasospasm following brain hemorrhage.

  2. Sixth hour transcutaneous bilirubin predicting significant hyperbilirubinemia in ABO incompatible neonates

    Institute of Scientific and Technical Information of China (English)

    Ramesh Y Bhat; Pavan CG Kumar

    2014-01-01

    Background: Neonates with ABO hemolytic disease are at greater risk for developing significant hyperbilirubinemia. We aimed to determine whether sixth hour transcutaneous bilirubin (TcB) could predict such a risk. Methods: TcB measurements were obtained at the 6th hour of life in blood group A or B neonates born to blood group O, rhesus factor compatible mothers. Subsequent hyperbilirubinemia was monitored and considered significant if a neonate required phototherapy/exchange transfusion. The predictive role of sixth hour TcB was estimated. Results: Of 144 ABO incompatible neonates, 41(OA, 24; O-B, 17) had significant hyperbilirubinemia. Mean sixth hour TcB was significantly higher among neonates who developed significant hyperbilirubinemia than those who did not (5.83±1.35 mg/dL vs. 3.65±0.96 mg/dL, P4 mg/dL had the highest sensitivity of 93.5% and >6 mg/dL had the highest specifi city of 99%. Area under receiver operating characteristic curve was 0.898. Conclusion: Sixth hour TcB predicts subsequent significant hyperbilirubinemia in ABO incompatible neonates.

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

    Science.gov (United States)

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

    2016-04-01

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

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

    Science.gov (United States)

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

    2009-08-01

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

  5. Is bilirubin able to affect the cell cycle in Gunn rat brain? - An in vivo and in vitro study -

    OpenAIRE

    Robert, Maria Celeste

    2012-01-01

    The hyperbilirubinemic jj Gunn rat is a well established animal model for Crigler-Najjar type I Syndrome and neonatal jaundice. Similarly to humans, they present neurological deficits and what is more a marked cerebellar hypoplasia with a prominent loss and degeneration of Purkinje cells and granule neurons. Since high levels of bilirubin have been proven to arrest the cell cycle progression, we addressed the question if the cerebellar hypoplasia observed in the hyperbilirubinemic Gunn rat co...

  6. Effect of bilirubin on expression and localization of PGP and Mrp1 in the central nervous system

    OpenAIRE

    Gazzin, Silvia

    2008-01-01

    INTRODUZIONE A basse concentrazioni la bilirubina non coniugata (unconjugated bilirubin, UCB) prodotta dalla degradazione dell’emoglobina, sembra essere un potente anti-ossidante, mentre è estremamente dannosa ad alte concentrazioni, causando encefalopatia nei neonati con severo ittero. Il 70% dei bambini che presentano kernittero muoiono entro sette giorni di vita, mentre il 30% dei sopravvissuti manifesta irreversibili conseguenze come sordità, ritardo mentale e danni cerebrali perman...

  7. Analysis of observed values of glucose, creatinine, bilirubin and ALT examinations in Blood(Serum,Plasma) in hospital population

    OpenAIRE

    Soni, Heratkumar D.; Kapadia, Manisha P.; Modi, Kamal R.; Patel, Shaileshkumar M.; Saxena, Puneet

    2015-01-01

    Objectives: Find reference range by Hoffman's method and compare it with published reference range in standard textbooks.Method: Observed values (results) of glucose (FBS, RBS and PP2BS), creatinine, bilirubin (total and direct) and ALT were collected from LIS of biochemistry section of New civil hospital surat laboratory services. Data were analysed using computarised hoffman's method as described by Alex K, Claudiu B and David WS2. Reference range derived by computarised hoffman's method we...

  8. The Effects of Field Massage Technique on Bilirubin Level and the Number of Defecations in Preterm Infants

    Directory of Open Access Journals (Sweden)

    Soheila Karbandi

    2015-12-01

    Full Text Available Background: Hyperbilirubinemia is a common physiological problem in approximately 80% of preterm infants during the first week after birth. Increase in bowel movements reduces enterohepatic circulation and increases bilirubin excretion. Aim: This study aimed to evaluate the effects of Field massage technique on bilirubin level and the number of defecations in preterm infants Method: This clinical trial was performed on 80 preterm infants aged 30-36 weeks, who were hospitalized in neonatal intensive care units of Qaem, Imam Reza, and Ommolbanin hospitals of Mashhad, Iran, in 2011. The enrolled infants were randomized into intervention and control groups. The control group received the routine care, and the intervention group received a 15-minute massage twice a day (morning and evening, for five consecutive days. Field massage technique was applied by the researcher. The number of defecations and cutaneous bilirubin level were recorded on a daily basis until the sixth day after birth. Independent t-test and Mann-Whitney U test were performed to analyze the data, using SPSS version 14. Results: The mean age of the intervention and control groups was 17.2±4.5 and 17.1±4.5 hours, respectively. The mean level of cutaneous bilirubin in the intervention and control groups on the first and sixth days were not significantly different (10.7±1.5, 10.8±1.4, 13.4±2.0, and 13.4±2.6, respectively; the first day: P=0.67, the sixth day: P=0.98. The number of defecations on the fourth (P=0.01, fifth (P

  9. Inverse association between serum total bilirubin levels and diabetic peripheral neuropathy in patients with type 2 diabetes.

    Science.gov (United States)

    Kim, Eun Sook; Lee, Sung Won; Mo, Eun Young; Moon, Sung Dae; Han, Je Ho

    2015-11-01

    Several studies have suggested that bilirubin, a potent innate antioxidant, plays a protective role against cardiovascular and microvascular disease. This study investigated the association between serum concentrations of total bilirubin (TB) and the presence of diabetic peripheral neuropathy (DPN) in Korean diabetic patients. This cross-sectional study involved 1207 patients aged more than 30 years with type 2 diabetes. DPN was assessed according to clinical symptoms and physical examinations using Michigan Neuropathy Screening Instrument examination score, 10-g monofilament sensation, and current perception threshold. The subjects were stratified into gender-specific tertiles based on TB values, and the relationship between the TB values and DPN was analyzed. Compared with patients within the lowest TB tertile, those with higher TB levels consisted of patients with shorter duration of diabetes, lower HbA1c, better renal function, and less autonomic neuropathy, retinopathy, and albuminuria. Serum TB levels were inversely associated with DPN. In multivariate analysis for the development of DPN after adjusting for potential confounding factors including retinopathy, albuminuria, and autonomic neuropathy, the TB levels were inversely associated with the presence of DPN, both as a continuous variable [odds ratio (OR) per log standard deviation (SD) 0.79; 95% confidence interval (CI) 0.65-0.97; P = 0.022] and when categorized in tertiles (the highest vs. the lowest tertile; OR 0.63; 95% CI 0.40-0.99; P = 0.046). Low serum bilirubin levels are significantly associated with DPN, independently of classic risk factors and other microvascular complications. Further investigation is necessary to determine whether serum bilirubin has a prognostic significance on DPN.

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

    Science.gov (United States)

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

    2007-06-15

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

  11. Prognostic significance of pretreatment serum levels of albumin, LDH and total bilirubin in patients with non-metastatic breast cancer.

    Science.gov (United States)

    Liu, Xiaoan; Meng, Qing H; Ye, Yuanqing; Hildebrandt, Michelle A T; Gu, Jian; Wu, Xifeng

    2015-02-01

    Liver function tests (LFTs) have been reported as independent predictors of non-liver disease-related morbidity and mortality in general population and cancer patients. In this study, we evaluated the relationship between pretreatment serum LFTs and overall survival (OS) in non-metastatic Caucasian breast cancer patients. Seven LFTs, including albumin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase (LDH), total bilirubin and total protein, were measured in pretreatment serum from 2425 female Caucasian patients with newly diagnosed, histologically confirmed non-metastatic invasive breast cancer. Multivariate Cox model was used to estimate hazard ratio (HR) and 95% confidence interval (CI) for the association of individual LFTs with 5-year OS while adjusting for age, smoking status, pathological characteristics and treatment regimen. We found that serum albumin, LDH and total bilirubin were significantly associated with 5-year OS in multivariate Cox analyses. Patients with higher albumin level exhibited 45% reduced risk of death (HR = 0.55, 95% CI: 0.40-0.75) compared with those with lower albumin level. Patients with higher total bilirubin level had a nearly 40% reduction in the risk of death (HR = 0.62, 95% CI: 0.45-0.85) and patients with higher LDH levels had a 1.42-fold increased risk of death (HR = 1.42, 95% CI: 1.08-1.88). Furthermore, cumulative analysis showed a significant dose-response trend of significantly increasing risk of death with increasing number of unfavorable LFT levels. Our result highlighted the potential of using pretreatment serum levels of albumin, LDH and total bilirubin as prognostic factors for OS in patients with non-metastatic breast cancer.

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

    Science.gov (United States)

    King, Angela G.

    2009-08-01

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

  13. Cortical Visual Impairment

    Science.gov (United States)

    ... Frequently Asked Questions Español Condiciones Chinese Conditions Cortical Visual Impairment En Español Read in Chinese What is cortical visual impairment? Cortical visual impairment (CVI) is a decreased ...

  14. Investigation of the potential modulatory effect of biliverdin, carbon monoxide and bilirubin on nitrergic neurotransmission in the pig gastric fundus.

    Science.gov (United States)

    Colpaert, Erwin E; Timmermans, Jean-Pierre; Lefebvre, Romain A

    2002-12-20

    In porcine gastric fundus, we have investigated the colocalization of the bile pigment biosynthetic enzymes heme oxygenase-2 and biliverdin reductase with neuronal nitric oxide synthase (nNOS), the effect of carbon monoxide (CO) on fundic circular smooth muscle and the possible modulatory effect of the bile pigments biliverdin and bilirubin on CO-mediated relaxations and on nitrergic relaxation. Heme oxygenase-2 and biliverdin reductase immunoreactivity was present in all nNOS containing myenteric neurons. CO induced a concentration-dependent relaxation of fundic circular smooth muscle strips, which was completely blocked by the specific guanylate cyclase inhibitor 1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one (ODQ). 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole (YC-1), biliverdin and bilirubin strongly enhanced the amplitude of the CO-induced relaxation. Tin protoporphyrin had no effect on electrically induced nitrergic relaxation, but spectrophotometric analysis learned that incubation of porcine gastric fundus circular muscle strips with tin protoporphyrin did not influence heme oxygenase activity. In conclusion, our data suggest that nitrergic neurons in the pig gastric fundus are able to produce biliverdin and bilirubin, and that these agents potentiate the relaxant effect of CO, which is formed concomitantly with biliverdin by heme oxygenase-2.

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

    Science.gov (United States)

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

    2016-10-01

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

  16. Selective and sensitive detection of free bilirubin in blood serum using human serum albumin stabilized gold nanoclusters as fluorometric and colorimetric probe.

    Science.gov (United States)

    Santhosh, Mallesh; Chinnadayyala, Somasekhar R; Kakoti, Ankana; Goswami, Pranab

    2014-09-15

    We report here a fluorescence quenching based non-enzymatic method for sensitive and reliable detection of free bilirubin in blood serum samples using human serum albumin (HSA) stabilized gold nanoclusters (HSA-AuNCs) as fluorescent probe. The fluorescence of the nanoclusters was strongly quenched by bilirubin in a concentration dependent manner by virtue of the inherent specific interaction between bilirubin and HSA. A strong binding constant of 0.55×10(6) L mole(-1) between the HSA-AuNC and bilirubin was discerned. The nano clusters each with size ~1.0 nm (in diameter) and a core of Au18 were homogeneously distributed in HSA molecules as revealed from the respective high resolution transmission electron microscopic and mass spectroscopic studies. The fluorescence quenching phenomena which obeyed a simple static quenching mechanism, was utilized for interference free detection of bilirubin with minimum detection limit (DL) of 248±12 nM (S/N=3). The fluorescence response of HSA-AuNCs against bilirubin was practically unaltered over a wide pH (6-9) and temperature (25-50 °C) range. Additionally, peroxidase-like catalytic activity of these nanoclusters was exploited for colorimetric detection of bilirubin in serum sample with a DL of 200±19 nM by following the decrease in absorbance (at λ440 nm) of the reaction and its rate constant (Kp) of 2.57±0.63 mL μg(-1) min(-1). Both these fluorometric and colorimetric methods have been successfully used for detection of free bilirubin in blood serum samples.

  17. PREDICTION OF SIGNIFICANT NEONATAL HYPERBILIRUBINAEMIA IN HEALTHY TERM NEW BORNS USING 22-26 HOURS’ SPECIFIC SERUM BILIRUBIN – A PROSPECTIVE STUDY

    OpenAIRE

    Reddy, MR; Swathi; Sangamitra; Pratap Rao; Sugunakar; Mohd. Nasir

    2016-01-01

    INTRODUCTION Hyperbilirubinemia invariably occurs in the newborns and is discerned as clinical jaundice in nearly 50% of infants. It is a cause of concern not only for the parents but also for the paediatricians. Bilirubin production is 2-3 times higher in normal term newborns compared with adults. The colour in jaundice usually results from accumulation of unconjugated, non-polar, lipid soluble, bilirubin pigment in the skin which is formed from haemoglobin by the action of h...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-08-01

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

  19. Noise exposure and public health

    NARCIS (Netherlands)

    Passchier-Vermeer, W.; Passchier, W.F.

    2000-01-01

    Exposure to noise constitutes a health risk. There is sufficient scientific evidence that noise exposure can induce hearing impairment, hypertension and ischemic heart disease, annoyance, sleep disturbance, and decreased school performance. For other effects such as changes in the immune system and

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

    Directory of Open Access Journals (Sweden)

    Andrea Müllebner

    2015-04-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-11-15

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

  2. Study on correlation among three kinds of bilirubin detection method%三种胆红素检测方法相关性研究

    Institute of Scientific and Technical Information of China (English)

    李守卫; 姚强

    2013-01-01

    目的 探讨三种胆红素检测方法的相关性.方法 选取生后7d内目测存在黄疸的住院新生儿50例,抽取血清标本用生化法测定血清总胆红素值,并同步以微量法和经皮法测定胆红素值,分别计算经皮胆红素值(TcB)与静脉血总胆红素值、末梢微量血胆红素值、静脉血总胆红素值之间的相关系数、检验其统计学意义.结果 末梢微量血胆红素检测法、经皮胆红素检测法分别与静脉血生化法均有很好的相关性(r=0.948、0.935,均P<0.01),并且末梢微量血胆红素检测法与静脉血生化法相关性更好.结论 采用微量血测定法检测胆红素值,不失为一种操作简便、结果可靠的方法.%Objective To explore which operation and the accuracy of the detection method is better by exploring the correlation among three bilirubin detection methods.Methods 50 hospitalized neonates within 7 days after birth with visual jaundice were randomly selected.The total serum bilirubin level was measured by the routine laboratory method.At the same time,the serum bilirubin level was measured by bilirubin analyzer for capillary blood and transcutaneous bilirubin(TcB) measurement,then calculated the linear correlation coefficient of TcB level and TSB level,capillary blood bilirubin level and TSB level respectively to analyze their statistical significance,and get the linear regression model at last.Results Close correlation is existed between the capillary blood bilirubin measurement and the routine laboratory method,also the transcutaneous bilirubin measurement and the routine laboratory method.Moreover,the former is better than the later.Conclusion Capillary blood bilirubin is reliable in measuring serum bilirubin level of newborns.

  3. Comparison of different methods in detection of neonatal bilirubin%不同方法对新生儿胆红素测定的比较

    Institute of Scientific and Technical Information of China (English)

    符宝铭; 韦蓉; 石明芳; 杨广林; 闫芳; 黄战; 周春浪; 欧珊

    2011-01-01

    Objective: To explore the differences of neonatal bilirubin detection with different methods, find a good method to monitor the dynamic changes of neonatal bilirubin. Methods; Three methods including automatic biochemical analyzer (biochemical method) , trace bilirubin analyzer (micromethod) and percutaneous bilirubin meter (percutaneous method) were used to detect the bilirubin levels of 90 neonates, then the differences were compared; micromethod and percutaneous method both were used to monitor the bilirubin levels of 392 normal full - term neonates at 1 ~7 days after birth dynamically, then the difference was compared. Results; There was no significant difference in measured value of bilirubin between micromethod and biochemical method ( P > 0. 05 ) ; when the level of bilirubin was less than 200 junol/L and within 201 -300 uJnol/L, there was no significant difference in measured value of bilirubin between percutaneous method and biochemical method (P >0.05); when the level of bilirubin was more than 300 jtmol/L, there was significant difference in measured value of bilirubin between percutaneous method and biochemical method (P < 0. 05) ; there was significant difference in measured value of bilirubin in neonates at 1 -7 days after birth between micromethod and percutaneous method (P <0. 05) . Conclusion; Micromethod is accurate and easy to operate in detection of neonatal bilirubin, which is superior to biochemical method and percutaneous method in dynamic monitoring of neonatal bilirubin.%目的:探讨不同方法对新生儿胆红素测定的差异,以寻找监测新生儿胆红素动态变化的好方法.方法:应用3种测定方法:全自动生化分析仪(生化法)、微量胆红素测定仪(微量法)、经皮测胆仪(经皮法)对90例新生儿进行胆红素测定并比较其差异,用微量法和经皮法同时对392例正常足月新生儿生后1~7天胆红素进行动态监测并比较其差异.结果:微量法胆红素测定值与生

  4. Inhibition of cholesterol crystallization under bilirubin deconjugation: partial characterization of mechanisms whereby infected bile accelerates pigment stone formation.

    Science.gov (United States)

    Nakai, Kuniharu; Tazuma, Susumu; Nishioka, Tomoji; Chayama, Kazuaki

    2003-06-10

    Pigment gallstones have been reported to be closely associated with biliary tract infection. We previously reported that addition of unconjugated bilirubin (UCB), which is deconjugated by beta-glucuronidase in infected bile, could enhance cholesterol crystal formation in supersaturated model bile (MB). The present study evaluated the effect of beta-glucuronidase on the processes of pigment gallstone formation and cholesterol crystallization. Supersaturated MB (taurocholate/lecithin/cholesterol at 71:18:11, a total lipid concentration of 10.0 g/dl and a cholesterol saturation index (CSI) of 2.0) and native rat bile were mixed at a ratio of 3:1. Then, mixed bile was incubated with or without beta-glucuronidase and changes of the following parameters were investigated over time: (1) the UCB/total bilirubin ratio; (2) cholesterol crystal formation; (3) the precipitate weight and the cholesterol concentration in the precipitate and supernatant; and (4) the lipid distribution of vesicles in the supernatant. Compared with beta-glucuronidase-free bile, (1) beta-glucuronidase-containing bile showed a significant increase of the UCB/total bilirubin ratio, (2) as well as a significantly longer nucleation time (96+/-17.0 vs. 114+/-20.0) and fewer cholesterol crystals. (3) The precipitate weight and the cholesterol concentration in the precipitate were significantly increased, while the cholesterol concentration in supernatant was decreased. (4) When mixed bile was incubated with beta-glucuronidase, the cholesterol concentration in the vesicles was lower than in bile without beta-glucuronidase. The precipitate weight and the cholesterol concentration in the precipitate was increased by incubation with beta-glucuronidase, while cholesterol concentration was decreased in the supernatant (especially in the vesicles). This means that bile vesicles were more stable and it was more difficult for cholesterol crystals to form. Thus, the presence of beta-glucuronidase may inhibit the

  5. 关于胆红素升高的实验室检测与临床%Detection of bilirubin: from laboratory to clinical practice

    Institute of Scientific and Technical Information of China (English)

    王豪

    2012-01-01

    Jaundice (abnormal elevation of bilirubin) is common in clinical practice.At present bilirubin is detected by measuring total bilirubin (TB) and direct bilirubin (DB) in hospital.Indirect bilirubin (IB) is the difference of TB and DB.Direct bilirubin reflects mainly the conjugated bilirubin but they are not all equivalent.Indirect bilirubin and unconjugated bilirubin are the same condition.In clinical practice,the proportion of DB (or IB) in TB is more significant than their level of elevation.The cause of jaundice could be roughly determined by analyzing the proportion of DB (or IB) in TB.The methodology and quality of bilirubin detection are quite different in hospitals in our country.The proportion of DB aud IB in TB in detection of bilirubin is also quite different in hospitals.It leads to a big puzzle to the diagnosis and differential diagnosis of jaundice for clinical doctors.It is suggested that the quality control of bilirubin detection should be strengthened in laboratory in hospital.On the bases of strict quality control of bilirubin detection,proper adjustment of the proportion of DB and IB as to make it consistiug with clinical practice and pathogenesis of diseases,and making the proportion stable for long time are also suggested.%黄疸即胆红素异常升高在临床上很常见.目前医院检测胆红素通常测定血中的总胆红素和直接胆红素,而以总胆红素减去直接胆红素得到间接胆红素的数值.直接胆红素主要反映结合胆红素,但二者并不完全等同.与此类似,间接胆红素主要反映非结合胆红素.在临床上,对黄疸的诊断和鉴别诊断,直接胆红素(或间接胆红素)占总胆红素的比例较之胆红素升高的幅度更有意义.通过分析直接或间接胆红素的比例,往往可以对黄疸的原因做出大致的诊断和鉴别诊断.但目前各家医院检测胆红素的方法和水平差别较大,不同疾病状态下所测出的直接或间接胆红素的比

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-07-15

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

  7. PREDICTION OF SIGNIFICANT NEONATAL HYPERBILIRUBINAEMIA IN HEALTHY TERM NEW BORNS USING 22-26 HOURS’ SPECIFIC SERUM BILIRUBIN – A PROSPECTIVE STUDY

    Directory of Open Access Journals (Sweden)

    Reddy

    2016-03-01

    Full Text Available INTRODUCTION Hyperbilirubinemia invariably occurs in the newborns and is discerned as clinical jaundice in nearly 50% of infants. It is a cause of concern not only for the parents but also for the paediatricians. Bilirubin production is 2-3 times higher in normal term newborns compared with adults. The colour in jaundice usually results from accumulation of unconjugated, non-polar, lipid soluble, bilirubin pigment in the skin which is formed from haemoglobin by the action of heme oxygenase, biliverdin reductase and non-enzymatic reducing agents in the reticulo-endothelial cells. AIMS & OBJECTIVE To determine hour specific serum bilirubin (22-26 hrs which will predict, subsequent significant hyperbilirubinemia in healthy term newborns. MATERIALS & METHODS A total of 250 healthy full term newborns were enrolled into the study. First bilirubin estimation (TSB 1 was estimated at 22- 26 hrs. The neonates were followed up clinically every 12 hrs for 72 hrs (till discharge. Second bilirubin estimation (TSB S was done whenever clinical suspicion of jaundice was present (usually at 72 hours. Depending upon the TSB 1 value, the infants were evaluated by using two available protocols (Arbitrary cut off value of 5 mg/dl and average value of 4.06 mg%. Sensitivity, specificity, negative and positive predictive values and likelihood ratio of the test were calculated. P-value was used to determine the level of significance. RESULTS Of 250 neonates included in the study, 13 neonates developed hyperbilirubinemia and were subjected to phototherapy. No infants with average bilirubin value of ≤4.06 mg% developed subsequent hyperbilirubinemia. However, 2 infants with arbitrary cut off value of ≤5 mg/dl developed hyperbilirubinemia. There was significant difference in TSB I value of neonates who subsequently did and those who did not developed significant hyperbilirubinemia (P-value-<0.01. The negative predictive value to these two applied protocol is very high

  8. Evaluating the role of indirect bilirubin, urobilinogen and Shine AND Lal index as an alternative screening tool for beta thalassemia minor

    Directory of Open Access Journals (Sweden)

    Ridham A. Khanderia

    2015-06-01

    Methods: The present study was conducted on 100 (n=100 subjects in blood bank, department of pathology, government medical college Rajkot, Gujarat, India. In first group 50 subjects (Thalassemia minor were selected while in second group 50 (n2=50 normal individuals from hospital staff were selected. Complete-haemogram, serum-direct, indirect and total bilirubin, urine urobilinogen and their sensitivity and specificity were calculated. Results: Of the 50 cases in test group, 41 had higher Indirect Bilirubin level (>0.7 mg/dl, 35 had high urobilinogen level (>1 mg/dl. In control group out of 50 cases, 3 had high indirect bilirubin levels, 4 had high urobilinogen levels. Indirect-bilirubin had sensitivity of 82%, specificity of 94%. Urobilinogen showed sensitivity of 70% and specificity of 92%. Conclusion: Indirect bilirubin and urine-urobilinogen is a valuable, cost-effective screening test for beta-thalassemia-trait with sensitivity and specificity comparable to RBC indices. [Int J Res Med Sci 2015; 3(3.000: 730-737

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

    DEFF Research Database (Denmark)

    Ebbesen, Finn; Madsen, Poul H; Vandborg, Pernille K;

    2016-01-01

    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. MATERIALS: 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. RESULTS: 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...

  10. Visual Impairment, Including Blindness

    Science.gov (United States)

    ... Who Knows What? Survey Item Bank Search for: Visual Impairment, Including Blindness Links updated, April 2017 En ... doesn’t wear his glasses. Back to top Visual Impairments in Children Vision is one of our ...

  11. Exposure Forecaster

    Data.gov (United States)

    U.S. Environmental Protection Agency — The Exposure Forecaster Database (ExpoCastDB) is EPA's database for aggregating chemical exposure information and can be used to help with chemical exposure...

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

    Science.gov (United States)

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

    2015-01-01

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

  13. 非结合胆红素/白蛋白比值与脑干诱发电位相关性及对胆红素脑损伤预测价值%Correlation and predictive value between non conjugated bilirubin/albumin ratio and brain stem evoked potential in predicting bilirubin brain damage

    Institute of Scientific and Technical Information of China (English)

    扈志银; 郑小亮; 户振军

    2015-01-01

    目的:研究新生儿非结合胆红素/白蛋白比值与ABR相关性及对胆红素脑损伤的预测价值,为防治提供临床依据. 方法:以2013年1月至2014年12月在庆阳市妇幼保健院新生儿病房收住的113例足月高胆红素血症患儿为观察对象,检查血清总胆红素、非结合胆红素水平、计算总胆红素/白蛋白(B/A)、非结合胆红素/白蛋白(UCB/A)比值, ABR,并监测其伴随疾病. 结果:观察时间内,113例高胆红素血症的足月新生儿中合并胆红素脑病31例,无胆红素脑病患儿82例. 分析了B/A、UCB/A及ABR诊断胆红素脑病的灵敏度、特异性及Youden指数. 提示UCB/A及ABR作为诊断胆红素脑病的指标有一定价值. 结论:UCB/A值与ABR对胆红素脑损伤有诊断价值,可作为目前临床检测新生儿胆红素脑损伤的方法.%Objective:To study the predictive value of neonatal bilirubin/albumin ratio with ABR correlation to bilirubin brain damage in order to provide the clinical basis for the prevention and control. Methods:113 cases of full-term neonatal hyperbilirubinemia in Qingyang maternal and child care from Jan 2013 to Dec 2014 were checked levels of the serum total bilirubin and the combination of bilirubin, calculates ratio of total bilirubin/albumin(B/A) and the combination of bilirubin/albumin(UCB/A), ABR and its associated with disease. Results: In the observation period, there were 31 cases of bilirubin encephalopathy and no bilirubin encephalopathy of 82 cases. The sensitivity and specificity of B/A, UCB/A, ABR and Youden index in the diagnosis of neonatal hyperbilirubinemia were analyzed. Conclusion:UCB/A value and ABR have diagnostic value to the bilirubin brain damage, which can be used as a method to detect neonatal bilirubin brain injury at present.

  14. Virtual Reality Exposure and Imaginal Exposure in the Treatment of Fear of Flying: A Pilot Study

    Science.gov (United States)

    Rus-Calafell, Mar; Gutierrez-Maldonado, Jose; Botella, Cristina; Banos, Rosa M.

    2013-01-01

    Fear of flying (FF) is an impairing psychological disorder that is extremely common in developed countries. The most effective treatment for this particular type of phobia is exposure therapy. However, there are few studies comparing imaginal exposure (IE) and virtual reality (VR) exposure for the treatment of FF. The present study compared the…

  15. Mandatory notification of impaired doctors.

    Science.gov (United States)

    Beran, R G

    2014-12-01

    Mandatory reporting of impaired doctors is compulsory in Australasia. Australian Health Practitioner Regulation Agency guidelines for notification claim high benchmark though the Royal Australasian College of Surgeons and the Royal Australasian College of Physicians suggest they still obstruct doctors seeking help. Western Australia excludes mandatory reporting of practitioner-patients. This study examines reporting, consequences and international experiences with notification. Depressed doctors avoid diagnosis and treatment, fearing consequences, yet are more prone to marital problems, substance dependence and needing psychotherapy. South African research confirms isolation of impaired doctors and delayed seeking help with definable characteristics of those at risk. New Zealand data acknowledge: errors occur; questionable contribution from mandatory reporting; issues concerning competence assessment; favouring reporting to senior colleagues or self-intervention to compliance with mandatory reporting. UK found an anaesthetist guilty of professional misconduct for not reporting and sanctioned doctors regarding Harold Shipman. Australians are reluctant to report, fearing legalistic intrusion into care. Australian research confirmed definable characteristics for doctors with psychiatric illness or alcohol abuse. Exposure to legal medicine evokes personal disenchantment for doctors involved. Medicine poses barriers for impaired doctors. Spanish and UK doctors do not use general practitioners and may have suboptimal care. US and European doctors self-medicate using samples. US drug-dependent doctors also prescribe for spouses. Junior doctors are losing empathy with the profession. UK doctors favour private care, avoiding public scrutiny. NZ and Brazil created specific services for doctors, which appear effective. Mandatory reporting may be counterproductive requiring reappraisal.

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

    Institute of Scientific and Technical Information of China (English)

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

    2012-01-01

    AIM:To find a possible relationship between inflammation and CA19-9 tumor marker by analyzing data from patients with benign jaundice (BJ) and malignant jaundice (MJ).METHODS:All patients admitted for obstructive jaundice,in the period 2005-2009,were prospectively enrolled in the study,obtaining a total of 102 patients.On admission,all patients underwent complete standard blood test examinations including C-reactive protein (CRP),bilirubin,CA19-9.Patients were considered eligible for the study when they presented obstructive jaundice confirmed by instrumental examinations and increased serum bilirubin levels (total bilirubin > 2.0 mg/dL).The standard cut-off level for CA19-9 was 32 U/mL,whereas for CRP this was 1.5 mg/L.The CA19-9 level was adjusted by dividing it by the value of serum bilirubin or by the CRP value.The patients were divided into 2 groups,MJ and BJ,and after the adjustment a comparison between the 2 groups of patients was performed.Sensitivity,specificity and positive predictive values were calculated before and after the adjustment.RESULTS:Of the 102 patients,51 were affected by BJ and 51 by MJ.Pathologic CA19-9 levels were found in 71.7% of the patients.In the group of 51 BJ patients there were 29 (56.9%) males and 22 (43.1%) females with a median age of 66 years (range 24-96 years),whereas in the MJ group there were 24 (47%) males and 27 (53%) females,with a mean age of 70 years (range 30-92 years).Pathologic CA19-9 serum level was found in 82.3% of MJ.CRP levels were pathologic in 66.6% of the patients with BJ and in 49% with MJ.Bilirubin and CA19-9 average levels were significantly higher in MJ compared with BJ (P =0.000 and P =0.02),while the CRP level was significantly higher in BJ (P =0.000).Considering a CA19-9 cut-off level of 32 U/mL,82.3% in the MJ group and 54.9% in the BJ group were positive for CA19-9 (P =0.002).A CA19-9 cut-off of 100 U/mL increases the difference between the two groups:35.3% in BJ and 68.6

  17. Energy change in the formation of conjugated bilirubin: A possible responsive mechanism for liver cell pathology Cambio energético durante la conjugación de la bilirrubina: un posible mecanismo de lesión hepatocelular

    Directory of Open Access Journals (Sweden)

    V. Wiwanitkit

    2007-02-01

    Full Text Available Bilirubin is formed when red blood cells die and their hemoglobin is broken down within the macrophages into heme and globins. In the liver, bilirubin is conjugated with UDP-glucuronate, making it water-soluble diglucuronide. Concerning this conjugation, a molecule of bilirubin reacts with two molecules of glucoronic acid. However, the nature of this energy-consuming reaction in the formation of conjugated bilirubin has never been reported, and this can be important for its potential implication in hyperbilirubinemia. In this work, the author calculated the energy required by conjugated-bilirubin formation per molecule. The energy required for complex formation is -22 kCal/mol. The nature of this energy-producing reaction can be a good explanation. Increased energy delivery in conjugated hyperbilirubinemia in liver disease might be a responsive mechanism to hepatic damage.

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

    Science.gov (United States)

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

    2016-07-20

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

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

    Directory of Open Access Journals (Sweden)

    Borini Paulo

    1999-01-01

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

  20. 用于清除胆红素的磁性亲和分离方法%Study on Removal of Bilirubin with Magnetic Affinity Separation Technique

    Institute of Scientific and Technical Information of China (English)

    徐辉; 张国亮; 张凤宝; 王淑兰

    2003-01-01

    An affinity adsorbent, Cibacron Blue 3GA immobilized magnetic polyvinyl alcohol (PVA) microsphereswas used for bilirubin removal taking the advantage of easy separation of magnetic sorbent from the biosystem.Fe3 O4 superparamagnetic particles was synthesized with hydrothermal reaction of ferrous chloride (FeCl2) and ferricchloride (FeCl3). Such magnetic particles are then encapsulated in biocompatible PVA to form magnetic polymermicrospheres sized from 2 to 15 nm with hydroxyl groups on its surface. Cibacron Blue 3GA, a dye-ligand, wascovalently coupled with the polyvinyl alcohol through the nucleophilic reaction between the chloride of its triazinering and the hydroxyl groups of PVA molecules under alkaline condition. The affinity adsorbent carried 21.1 μmolCibacron Blue 3GA per gram magnetic polymer microspheres was used to remove unconjugated and conjugatedbilirubin from the solution which was composed of bilirubin or bilirubin and protein. After the adsorption, theadsorbent loaded with bilirubin was removed easily in the magnetic field.

  1. 新生儿胆红素脑病发病机制与临床评价%Pathogenesis and clinical evaluation of bilirubin encephalopathy in newborn infant

    Institute of Scientific and Technical Information of China (English)

    毛健

    2006-01-01

    @@ 新生儿时期严重的高胆红素血症,特别是生后1周内发生的严重高胆红素血症常易导致急性神经系统功能障碍,即急性胆红素脑病(Acute bilirubin encephalopathy,ABE).

  2. Effect of preoperative biliary drainage on surgical results after pancreaticoduodenectomy in patients with distal common bile duct cancer:Focused on the rate of decrease in serum bilirubin

    Institute of Scientific and Technical Information of China (English)

    Yun Mee Choi; Seok-Hwan Shin; Kyung Rae Kim; Ze-Hong Woo; Eung-Ho Cho; Keon-Young Lee; Seung-Ik Ahn; Sun Keun Choi; Sei Joong Kim; Yoon Seok Hut; Young Up Cho; Kee-Chun Hang

    2008-01-01

    AIM:To examine if the rate of decrease in serum bilirubin after preoperative biliary drainagecan be used as a predicting factor for surgical complications and postoperative recovery after pancreaticoduodenectomy in patients with distal common bile duct cancer.METHODS:A retrospective study was performed in 49 consecutive patients who underwent pancreaticoduodenectomy for distal common bile duct cancer.Potential risk factors were compared between the complicated and uncomplicated groups.Also,the rates of decrease in serum bilirubin were compared pre-and postoperatively.RESULTS:Preoperative biliary drainage (PBD) was performed in 40 patients (81.6%).Postoperative morbidity and mortality rates were 46.9% (23/49) and 6.1% (3/49),respectively.The presence or absence of PBD was not different between the complicated and uncomplicated groups.In patients with PBD,neither the absolute level nor the rate of decrease in serum bilirubin was significantly different.Patients with rapid decrease preoperatively showed faster decrease during the first postoperative week (5.5±4.4 μmol/L vs-1.7±9.9μmol/L,P=0.004).CONCLUSION:PBD does not affect the surgical outcome of pancreaticoduodenectomy in patients with distal common bile duct cancer.There is a certain group of patients with a compromised hepatic excretory function,which is represented by the slow rate of decrease in serum bilirubin after PBD.

  3. 新生儿胆红素脑病脑脊液胆红素及脑干听觉诱发电位检测的临床意义%The clinical significance of cerebrospinal fluid bilirubin and brainstem auditory evoked potential tests in neonatal bilirubin encephalopathy

    Institute of Scientific and Technical Information of China (English)

    李先红; 张健; 查萍; 王丽丽; 孔萤; 孙璐路; 郑洪

    2014-01-01

    Objective To explore the clinical significance of cerebrospinal fluid bilirubin level and brainstem auditory evoked poten -tial in neonatal bilirubin encephalopathy .Methods All the cases with hyperbilirubinemia were selected from July 2011 to July 2013 in our department,and were divided into the bilirubin encephalopathy group (44 cases) and the non-bilirubin encephalopathy group (79 cases).Ce-rebrospinal fluid ,serum bilirubin level and brainstem auditory evoked potential ( BAEP ) changes were compared between the two groups of children .Results The cerebrospinal fluid bilirubin level in bilirubin encephalopathy group was higher than that of non -bilirubin encephalopa-thy group [(11.0 +3.9) tendency/L vs (7.4 +4.0) tendency/L],and the difference was statistically significant (P<0.01).The inci-dence of abnormal BAEP (61.4%) in bilirubin encephalopathy group was higher than that of non-bilirubin encephalopathy group (16.5%), and the difference was statistically significant (P<0.01).Conclusion Cerebrospinal fluid bilirubin can be used as a reliable indicator for bilirubin encephalopathy in the early diagnosis ,and newborn infants with bilirubin encephalopathy accompanied by higher incidence of hearing damage require early intervention treatment .%目的:探讨新生儿胆红素脑病脑脊液胆红素水平及脑干听觉诱发电位(BAEP)检查的临床意义。方法选取高胆红素血症新生儿为研究对象,分为胆红素脑病组(44例)和非胆红素脑病组(79例),比较两组患儿脑脊液、血清胆红素水平以及BAEP变化。结果胆红素脑病组患儿脑脊液胆红素水平高于非胆红素脑病组[(11.0±3.9) mol/L VS (7.4±4.0) mol/L],差异有统计学意义(P<0.05);胆红素脑病组BAEP异常发生率(61.4%)高于非胆红素脑病组(16.5%),差异有统计学意义(P<0.01)。结论脑脊液胆红素水平检测可作为新生儿胆红素脑病早期诊断的可

  4. Co-Electrodeposition of Bilirubin Oxidase with Redox Polymer through Ligand Substitution for Use as an Oxygen Reduction Cathode

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Hyo Sul; Kang, Chan [Chonbuk National University, Jeonju (Korea, Republic of)

    2010-11-15

    The water soluble redox polymer, poly(N-vinylimidazole) complexed with Os(4,4'-dichloro-2,2'-bipyridine){sub 2}Cl]{sup +} (PVI-[Os(dCl-bpy){sub 2}Cl]{sup +}), was electrodeposited on the surface of a glassy carbon electrode by applying cycles of alternating square wave potentials between 0.2 V (2 s) and 0.7 V (2 s) to the electrode in a solution containing the redox polymer. The coordinating anionic ligand, Cl- of the osmium complex, became labile in the reduced state of the complex and was substituted by the imidazole of the PVI chain. The ligand substitution reactions resulted in crosslinking between the PVI chains, which made the redox polymer water insoluble and caused it to be deposited on the electrode surface. The deposited film was still electrically conducting and the continuous electrodeposition of the redox polymer was possible. When cycles of square wave potentials were applied to the electrode in a solution of bilirubin oxidase and the redox polymer, the enzyme was co-electrodeposited with the redox polymer, because the enzymes could be bound to the metal complexes through the ligand exchange reactions. The electrode with the film of the PVI-[Os(dCl-bpy){sub 2}Cl]{sup +} redox polymer and the co-electrodeposited bilirubin oxidase was employed for the reduction of O{sub 2} and a large increase of the currents was observed due to the electrocatalytic O{sub 2} reduction with a half wave potential at 0.42 V vs. Ag/AgCl.

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

    Science.gov (United States)

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

    2015-09-01

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

  6. 血清胆红素与代谢综合征的相关性研究%Relationship Between Serum Bilirubin and Metabolic Syndrome

    Institute of Scientific and Technical Information of China (English)

    韩硕; 张壬; 金元哲

    2015-01-01

    Objective] To explore the correlation between serum bilirubin and metabolic syndrome (MS) .[Methods] A total of 2 ,125 participants in our survey of atherosclerosis and related diseases were recruited to complete questionnaire ,physical examinations and laboratory tests .They were divided into metabolic syndrome (MS) and non‐metabolic syndrome (NMS) groups according to the International Diabetes Federation (IDF) diag‐nostic criteria for MS .And the correlations were analyzed for MS and serum total bilirubin ,direct bilirubin and in‐direct bilirubin .[Results] Their age range was 35~64 years .With an overall incidence rate of MS of 36 .1% ,it was higher in females than males (43 .5% vs 18 .4% ,P <0 .01) .Direct bilirubin was higher in MS group than that in NMS group [(2 .07 ± 0 .86) vs (2 .29 ± 0 .96)μmol/L ,P <0 .01] .With a rising number of MS composi‐tion factors ,bilirubin levels decreased .Among MS individuals ,serum total bilirubin and direct bilirubin levels were higher in males than those in females ( P<0 .05) .Logistic regression analysis showed that a low direct bili‐rubin level was more susceptible to MS .[Conclusion]Serum bilirubin may be associated with MS and direct biliru‐bin has greater correlations with MS .Individuals with lower serum direct bilirubin levels are more susceptible to MS .%【目的】研究血清胆红素与代谢综合征(MS)的相关性。【方法】对参与辽宁省沈阳市城区动脉硬化及其相关疾病调查的居民进行问卷调查、体格检查和实验室检查,依据国际糖尿病联盟诊断标准将其分为MS组及非代谢综合征(NMS)组。分析受试者血清总胆红素(TBIL)、直接胆红素(DBIL)及间接胆红素(IBIL)与MS的相关性。【结果】共纳入2125名35~64周岁居民,MS的总发生率为36.1%,女性高于男性(43.5%vs18.4%,P<0.01)。MS组DBIL浓度低于NMS组[(2.07±0.86)μmol/Lvs(2.29±0.96

  7. Relationship between serum bilirubin and diabetic kideny disease in patients with type 2 diabetes%2型糖尿病患者血清胆红素水平与糖尿病肾病关系的研究

    Institute of Scientific and Technical Information of China (English)

    陈宇; 周永华; 韩晓骏; 严冲; 苏如婷; 李小飞

    2011-01-01

    目的 探讨2型糖尿病(type 2 diabetes mellitus,T2DM)患者血清胆红素水平与糖尿病肾病(diabetickidney disease,DKD)之间的关系.方法 789例T2DM患者,按照24小时尿白蛋白定量分为正常尿白蛋白组(尿白蛋白300 mg),并以168例正常成人作为对照组,观察各组之间血清胆红素的差异,探讨血清胆红素水平与DKD的关系.结果 T2DM患者血清总胆红素、直接胆红素和间接胆红素水平均低于正常对照组(P0.05);临床尿白蛋白组的总胆红素、直接胆红素以及间接胆红素均低于其他两组(P0.05;r=-0.106,P0.05;r=0.12,P<0.05.结论 胆红素可能是T2DM患者肾脏的保护性因子.糖尿病早期采取积极的抗氧化治疗对防止DKD的发生发展有重要意义.%Objective To approach the relationship between serum bilirubin level and diabetic kideny disease in patients with type 2 diabetes mellitus(T2DM).Methods 789 T2DM patients were classified into normoalbuminuria group (urinary albumin excretion less than 30 mg per 24 h), microalbuminuria group (urinary albumin excretion range from 30 to 300 mg per 24 h) and macroalbuminuria group (urinary albumin excretion more than 300 mg per 24 h) according to the degree of urinary albumin excretion.We chose 168 healthy adults randomly as the control group.The difference in serum bilirubin among groups and the correlation between serum bilirubin and diabetic nephropathy were analyzed.Results T2DM group had higher levels of serum total bilirubin, direct bilirubin and unconjugated bilirubin significantly than those of the control group ( P <0.01 or P <0.05).The total bilirubin and unconjugated bilirubin levels of the microalbuminuria group were lower compared with those of the normoalbuminuria group ( P <0.01, P < 0.05), while there was no significant difference in the direct bilirubin (P >0.05).Compared with the other two groups, the macroalbuminuria group had lower serum total bilirubin, direct bilirubin as well as

  8. Influence of curcumin on cyclosporin-induced reduction of biliary bilirubin and cholesterol excretion and on biliary excretion of cyclosporin and its metabolites.

    Science.gov (United States)

    Deters, M; Siegers, C; Hänsel, W; Schneider, K P; Hennighausen, G

    2000-06-01

    We investigated the ability of curcumin, which can be extracted from different Curcuma species, to prevent cyclosporin-induced reduction of biliary bilirubin and cholesterol excretion, and its influence on biliary excretion of cyclosporin (CS) and its metabolites in the bile fistula model in rats. I.v. injection of curcumin (25 and 50 mg/kg) after 30 min increased dose-dependently basal bile flow (30 microliters/kg/min) up to 200%, biliary bilirubin excretion (3000 pmol/kg/min) up to 150%, and biliary cholesterol excretion (22 nmol/kg/min) up to 113%. CS (30 mg/kg) reduced bile flow to 66% and biliary excretion of bilirubin and of cholesterol to 33% of the basal value 30 min after i.v. injection. I.v. administration of curcumin (25 and 50 mg/kg) 30 min after CS increased bile flow dose dependently again to 130% for 1 hour and biliary excretion of cholesterol and of bilirubin to 100% of the basal value for 30 and 150 min, respectively. Injection of curcumin 15 min before CS prevented the CS-induced drop of bile flow at 50 mg/kg and reduction of biliary bilirubin excretion already at 25 mg/kg until the end of the experiment (180 min). The CS-induced reduction of biliary cholesterol excretion, however, was not prevented by curcumin. Finally, the biliary excretions of CS (1200 ng/kg/min) and its metabolites (1200 ng/kg/min) were slightly reduced by curcumin at a dose of 50 mg/kg (to 83% of the initial values). The clinical importance of these controversial effects remains to be shown.

  9. 胆红素对凝血功能检测结果的影响%Influence of bilirubin on the coagulation function test results

    Institute of Scientific and Technical Information of China (English)

    刘淑芹

    2015-01-01

    目的:探讨不同胆红素浓度对血浆凝血酶原时间(PT)和活化部分凝血活酶时间(APTT)检测结果的影响.方法:对含有不同总胆红素浓度的质控血浆进行血浆凝血酶原时间和活化部分凝血活酶时间指标测定,比较不同浓度的胆红素对上述指标的影响.结果:随着血浆总胆红素浓度的升高,PT、APTT检测结果升高,胆红素水平低于20 μmol/L时,对血浆PT、APTT测定结果影响的差异无统计学意义(P>0.05),当胆红素浓度高于41 μmol/L时,APTT检测结果显著高于对照血浆水平(P0.05).When the bilirubin concentration was more than 41 μmol/L,the APTT test result was significantly higher than the controlled plasma level(P<0.05).When the bilirubin concentration was more than 62 μ mol/L,the PT test result was significantly higher than the controlled plasma level(P<0.05).Conclusion:When the bilirubin level is less than 20 μ mol/L,the influence on the coagulation function test results is not big.However the plasma bilirubin concentration is significantly increased,it has distraction on the PT and APTT test results.When simply because of elevated bilirubin levels lead to PT, APTT results abnormal increase,it could be used the regression equation for correction to provide more accurate detection results in clinic.

  10. Conjugated bilirubin affects cytokine profiles in hepatitis A virus infection by modulating function of signal transducer and activator of transcription factors.

    Science.gov (United States)

    Castro-García, Flor P; Corral-Jara, Karla F; Escobedo-Melendez, Griselda; Sandoval-Hernandez, Monserrat A; Rosenstein, Yvonne; Roman, Sonia; Panduro, Arturo; Fierro, Nora A

    2014-12-01

    Hepatitis A virus (HAV) infection is the major cause of acute liver failure in paediatric patients. The clinical spectrum of infection is variable, and liver injury is determined by altered hepatic enzyme function and bilirubin concentration. We recently reported differences in cytokine profiles between distinct HAV-induced clinical courses, and bilirubin has been recognized as a potential immune-modulator. However, how bilirubin may affect cytokine profiles underlying the variability in the course of infection has not been determined. Herein, we used a transcription factor (TF) binding site identification approach to retrospectively analyse cytokine expression in HAV-infected children and to predict the entire set of TFs associated with the expression of specific cytokine profiles. The results suggested that modulation of the activity of signal transducers and activators of transcription proteins (STATs) may play a central role during HAV infection. This led us to compare the degree of STAT phosphorylation in peripheral blood lymphoid cells (PBLCs) from paediatric patients with distinct levels of conjugated bilirubin (CB). Low CB levels in sera were associated with increased STAT-1 and STAT-5 phosphorylation. A positive correlation was observed between the serum interleukin-6 (IL-6) content and CB values, whereas higher levels of CB correlated with reduced serum IL-8 values and with a reduction in the proportion of PBLCs positive for STAT-5 phosphorylation. When CB was used to stimulate patients' PBLCs in vitro, the levels of IL-6 and tumour necrosis factor-α were increased. The data showed that bilirubin plays a role in STAT function and affects cytokine profile expression during HAV infection.

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

    Science.gov (United States)

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

    2014-02-21

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

  12. Endothelial cells derived from the blood-brain barrier and islets of Langerhans differ in their response to the effects of bilirubin on oxidative stress under hyperglycemic conditions

    Directory of Open Access Journals (Sweden)

    Jaime eKapitulnik

    2012-07-01

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

  13. Development or Impairment?

    Science.gov (United States)

    Hakansson, Gisela

    2010-01-01

    Joanne Paradis' Keynote Article on bilingualism and specific language impairment (SLI) is an impressive overview of research in language acquisition and language impairment. Studying different populations is crucial both for theorizing about language acquisition mechanisms, and for practical purposes of diagnosing and supporting children with…

  14. Specific Language Impairment

    Science.gov (United States)

    ... impairments. After studying a large group of Hispanic children who speak English as a second language, NIDCD-funded researchers have developed a dual language diagnostic test to identify bilingual children with language impairments. It’s now being tested in ...

  15. Occupational solvent exposure and cognition

    Science.gov (United States)

    Sabbath, E.L.; Glymour, M.M.; Berr, C.; Singh-Manoux, A.; Zins, M.; Goldberg, M.

    2012-01-01

    Objective: Chronic occupational solvent exposure is associated with long-term cognitive deficits. Cognitive reserve may protect solvent-exposed workers from cognitive impairment. We tested whether the association between chronic solvent exposure and cognition varied by educational attainment, a proxy for cognitive reserve. Methods: Data were drawn from a prospective cohort of French national gas and electricity (GAZEL) employees (n = 4,134). Lifetime exposure to 4 solvent types (chlorinated solvents, petroleum solvents, benzene, and nonbenzene aromatic solvents) was assessed using a validated job-exposure matrix. Education was dichotomized at less than secondary school or below. Cognitive impairment was defined as scoring below the 25th percentile on the Digit Symbol Substitution Test at mean age 59 (SD 2.8; 88% of participants were retired at testing). Log-binomial regression was used to model risk ratios (RRs) for poor cognition as predicted by solvent exposure, stratified by education and adjusted for sociodemographic and behavioral factors. Results: Solvent exposure rates were higher among less-educated patients. Within this group, there was a dose-response relationship between lifetime exposure to each solvent type and RR for poor cognition (e.g., for high exposure to benzene, RR = 1.24, 95% confidence interval 1.09–1.41), with significant linear trends (p < 0.05) in 3 out of 4 solvent types. Recency of solvent exposure also predicted worse cognition among less-educated patients. Among those with secondary education or higher, there was no significant or near-significant relationship between any quantification of solvent exposure and cognition. Conclusions: Solvent exposure is associated with poor cognition only among less-educated individuals. Higher cognitive reserve in the more-educated group may explain this finding. PMID:22641403

  16. 新生儿胆红素脑病33例临床分析%A retrospective study of neonatal severe bilirubin encephalopathy in 33 newborns

    Institute of Scientific and Technical Information of China (English)

    徐瑞峰; 吴珠明; 高红霞; 易彬

    2011-01-01

    目的 探讨新生儿胆红素脑病的病因及临床特点.方法 选择2006年1月至2010年1月我院新生儿科收治的重症新生儿高胆红素血症患儿,分为胆红素脑病组(脑病组)与非胆红素脑病组(非脑病组),比较两组患儿病因、临床特征、胆红素水平、胆红素/白蛋白比值(B/A)以及治疗转归.结果 脑病组黄疸病因以溶血性因素占首位(48.5%),其次是感染因素(24.2%);非脑病组黄疸病因主要为溶血(69.7%).脑病组总胆红素、B/A比值、入院日龄和黄疸持续时间均大于非脑病组[( 555.2±113.9) μmol/L比(431.3±62.3)μmol/L,(0.87±0.17)比(0.67±0.11),(129.5±60.7)h比(53.0±22.6)h,(81.6±39.6)h比(34.2±15.8)h,P均<0.001].胆红素脑病警告期与痉挛期患儿入院日龄、血清胆红素及B/A比值差异无统计学意义(P>0.05).85%的胆红素脑病患儿预后不良.结论 溶血与感染是新生儿胆红素脑病的主要原因,总胆红素浓度过高和干预延迟是引起胆红素脑病的高危因素.%Objective To investigate the etiology and clinical features of neonatal bilirubin encephalopathy. Methods To select severe hyperbilirubinemia infant admitted in Gansu Provincial Maternity and Children's Hospital from January 2006 to January 2010, assigned into encephalopathy group and non-encephalopathy group, comparing their clinical characteristics, bilirubin level, bilirubin/ albumin ratio (B/A) and outcome. Results The main etiology of neonatal bilirubin encephalopathy is hemolytic (48. 5% ) , followed by infection (24. 2% ) ; but the etiology of non-encephalopathy is mainly for hemolysis, accounted for 69. 7%. Total bilirubin, B/A ratio, admission day and jaundice duration of Encephalopathy group are larger than them in non-encephalopathy group, the difference was statistically significant, (555. 2 ±113. 9) μmol/Lvs. (431. 3 ±62. 3) |xmol/L, (0.87 ±0.17) us. (0.67 ±0. 11) , (129.5 ±60.7) h ts. (53.0 ±22.6) h and (81.6 ±39.6) h

  17. 新生儿胆红素脑病脑脊液总胆红素及颅脑MRI检查的临床意义%Clinical Significance of Cerebrospinal Fluid Bilirubin and Craniocerebral Magnetic Resonance Imaging Measurements in Newborns with Bilirubin Encephalopathy

    Institute of Scientific and Technical Information of China (English)

    李先红; 张健; 郑洪; 孔萤; 孙路璐; 刘光辉

    2014-01-01

    Objective To explore the clinical significance of changes in cerebrospinal fluid bilirubin levels and craniocerebral magnetic resonance imaging (MRI)features in newborns with bilir-ubin encephalopathy. Methods Total bilirubin levels in serum and cerebrospinal fluid were determined using vanadate oxidation method with automatic biochemical analyzer in 44 newborns with bilirubin encephalopathy (bilirubin encephalopathy group)and 79 newborns without bilirubin enceph-alopathy (non-bilirubin encephalopathy group).In addition,craniocerebral MRI was performed in both groups. Results Total bilirubin levels in serum and cerebrospinal fluid in bilirubin encephalopathy group were significantly higher than those in non-bilirubin encephalopathy group (P<0.01).In bilirubin enceph-alopathy group,MRI showed symmetrical high signal intensity in the globus pallidus on T1WI in 33 newborns,abnormal signal in lateral side of posterior limb of internal capsule in the right basal ganglion region in 1 newborn,high signal intensity in the head of the right caudate nucleus on T1WI in 1 newborn, abnormal signal in the lateral ventricle in 3 newborns,abnormal signal in the bilateral frontal lobes in 1 newborn, short T1T2 signal in the torcular herophili in 1 newborn,and normal signal in 4 newborns. In non-bilirubin encephalopathy group,MRI showed symmetrical high signal intensity in the globus pallidus on T1WI in 3 newborns, abnormal signal in the right side of top occipital in 1 newborn, and normal signal in 75 newborns. The incidence of symmetrical high T1WI signal intensity in the globus pallidus in bilirubin encephalopathy group was significantly higher than that in non-bilirubin encephalopathy group (P<0.01).Conclusion Cerebrospinal fluid bilirubin can be used as a reliable indicator for the early diagnosis of bilirubin encephalopathy. The symmetrical high signal intensity in the globus pallidus on T1WI is the main feature of bilirubin encephalopathy in newborns. Regular fol-low-up and

  18. Vascular Cognitive Impairment.

    Science.gov (United States)

    Dichgans, Martin; Leys, Didier

    2017-02-03

    Cerebrovascular disease typically manifests with stroke, cognitive impairment, or both. Vascular cognitive impairment refers to all forms of cognitive disorder associated with cerebrovascular disease, regardless of the specific mechanisms involved. It encompasses the full range of cognitive deficits from mild cognitive impairment to dementia. In principle, any of the multiple causes of clinical stroke can cause vascular cognitive impairment. Recent work further highlights a role of microinfarcts, microhemorrhages, strategic white matter tracts, loss of microstructural tissue integrity, and secondary neurodegeneration. Vascular brain injury results in loss of structural and functional connectivity and, hence, compromise of functional networks within the brain. Vascular cognitive impairment is common both after stroke and in stroke-free individuals presenting to dementia clinics, and vascular pathology frequently coexists with neurodegenerative pathology, resulting in mixed forms of mild cognitive impairment or dementia. Vascular dementia is now recognized as the second most common form of dementia after Alzheimer's disease, and there is increasing awareness that targeting vascular risk may help to prevent dementia, even of the Alzheimer type. Recent advances in neuroimaging, neuropathology, epidemiology, and genetics have led to a deeper understanding of how vascular disease affects cognition. These new findings provide an opportunity for the present reappraisal of vascular cognitive impairment. We further briefly address current therapeutic concepts.

  19. INVESTIGATION ON ASSOCIATION OF SERUM BILIRUBIN CONCENTRATION WITH RISK OF CORONARY HEART DISEASE%血清胆红素与冠心病的关系探讨

    Institute of Scientific and Technical Information of China (English)

    张书亚; 陈红涛

    2001-01-01

    Objective  To investigate the relationship between of serum bilirubin concentrations and risk of coronary heart drsease (CHD). Methods  Serum bilirubin concentrations were determined in 12 cases with acute myocardial infarction(AMI)、37 cases with unstable angina pectoris (UAP) and 30 cases with UAP with arrhythmia. Results  The serum total bilirubin(TB)、direct bilirubin(DB)、indirect bilirubin(IB) concentrations were lower in the three study groups of CHD than in the controls. There was significant difference between the patients with CHD and the controls. However, there was no significant difference among the three study groups of CHD. Conclusion  Serum bilirubin concentrations was inversely and statistically significantly related to risk of CHD.%目的探讨血清胆红素浓度与冠心病(CHD)发生的危险性之间的关系。方法观察79例CHD患者血清胆红素浓度,再据冠心病分型将其分为急性心肌梗死(AMI)组12例,不稳定型心绞痛(UAP)组37例,不稳定型心绞痛并心律失常组30例。同时观察30例健康体检组血清胆红素浓度。结果冠心病组及不同类型冠心病组血清总胆红素、直接胆红素、间接胆红素浓度均降低,与健康对照组比较均有显著性差异,而不同类型冠心病组间比较差异无显著性。结论血清胆红素浓度与冠心病发生的危险性之间呈显著的负相关。

  20. Adolescent exposure to nicotine and/or the cannabinoid agonist CP 55,940 induces gender-dependent long-lasting memory impairments and changes in brain nicotinic and CB(1) cannabinoid receptors.

    Science.gov (United States)

    Mateos, B; Borcel, E; Loriga, R; Luesu, W; Bini, V; Llorente, R; Castelli, M P; Viveros, M-P

    2011-12-01

    We have analysed the long-term effects of adolescent (postnatal day 28-43) exposure of male and female rats to nicotine (NIC, 1.4 mg/kg/day) and/or the cannabinoid agonist CP 55,940 (CP, 0.4 mg/kg/day) on the following parameters measured in the adulthood: (1) the memory ability evaluated in the object location task (OL) and in the novel object test (NOT); (2) the anxiety-like behaviour in the elevated plus maze; and (3) nicotinic and CB(1) cannabinoid receptors in cingulated cortex and hippocampus. In the OL, all pharmacological treatments induced significant decreases in the DI of females, whereas no significant effects were found among males. In the NOT, NIC-treated females showed a significantly reduced DI, whereas the effect of the cannabinoid agonist (a decrease in the DI) was only significant in males. The anxiety-related behaviour was not changed by any drug. Both, nicotine and cannabinoid treatments induced a long-lasting increase in CB(1) receptor activity (CP-stimulated GTPγS binding) in male rats, and the nicotine treatment also induced a decrease in nicotinic receptor density in the prefrontal cortex of females. The results show gender-dependent harmful effects of both drugs and long-lasting changes in CB(1) and nicotinic receptors.

  1. Stormwater Impaired Watersheds

    Data.gov (United States)

    Vermont Center for Geographic Information — Stormwater impaired watersheds occuring on both the Priority Waters (Part D - Completed TMDL) and 303(d) list of waters (Part A - need TMDL) The Vermont State...

  2. Impairments to Vision

    Science.gov (United States)

    ... an external Non-Government web site. Impairments to Vision Normal Vision Diabetic Retinopathy Age-related Macular Degeneration In this ... pictures, fixate on the nose to simulate the vision loss. In diabetic retinopathy, the blood vessels in ...

  3. Speech impairment (adult)

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003204.htm Speech impairment (adult) To use the sharing features on ... 2017, A.D.A.M., Inc. Duplication for commercial use must be authorized in writing by ADAM ...

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

    Directory of Open Access Journals (Sweden)

    Maria das Graças da Cunha Leite

    2003-01-01

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

  5. Electrochemical characterization of adsorbed bilirubin oxidase on Vulcan XC 72R for the biocathode preparation in a glucose/O{sub 2} biofuel cell

    Energy Technology Data Exchange (ETDEWEB)

    Habrioux, A.; Napporn, T.; Servat, K. [LACCO ' Equipe Electrocatalyse' UMR 6503 CNRS-Universite de Poitiers, 40 av. du Recteur Pineau 86022 Poitiers (France); Tingry, S. [Institut Europeen des Membranes, UMR 5635, Place Eugene Bataillon, CC 047, 34095 Montpellier, cedex 5 (France); Kokoh, K.B., E-mail: boniface.kokoh@univ-poitiers.f [LACCO ' Equipe Electrocatalyse' UMR 6503 CNRS-Universite de Poitiers, 40 av. du Recteur Pineau 86022 Poitiers (France)

    2010-11-01

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

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

    Science.gov (United States)

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

    2014-01-01

    Spirulina platensis is a blue-green alga used as a dietary supplement because of its hypocholesterolemic properties. Among other bioactive substances, it is also rich in tetrapyrrolic compounds closely related to bilirubin molecule, a potent antioxidant and anti-proliferative agent. The aim of our study was to evaluate possible anticancer effects of S. platensis and S. platensis-derived tetrapyrroles using an experimental model of pancreatic cancer. The anti-proliferative effects of S. platensis and its tetrapyrrolic components [phycocyanobilin (PCB) and chlorophyllin, a surrogate molecule for chlorophyll A] were tested on several human pancreatic cancer cell lines and xenotransplanted nude mice. The effects of experimental therapeutics on mitochondrial reactive oxygen species (ROS) production and glutathione redox status were also evaluated. Compared to untreated cells, experimental therapeutics significantly decreased proliferation of human pancreatic cancer cell lines in vitro in a dose-dependent manner (from 0.16 g•L-1 [S. platensis], 60 μM [PCB], and 125 μM [chlorophyllin], palga. Furthermore, it seems that dietary supplementation with this alga might enhance systemic pool of tetrapyrroles, known to be higher in subjects with Gilbert syndrome.

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

    Science.gov (United States)

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

    2015-11-01

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

  8. Decolorization of anthraquinone-type dye by bilirubin oxidase-producing nonligninolytic fungus Myrothecium sp. IMER1.

    Science.gov (United States)

    Zhang, Xiaoyu; Liu, Youxun; Yan, Keliang; Wu, Hangjun

    2007-08-01

    The decolorization of an anthraquinone dye, Remazol Brilliant Blue R (RBBR), was carried out using a new isolated nonligninolytic fungus, strain Myrothecium sp. IMER1. In potato dextrose broth (PDB) containing RBBR, this strain was able to grow and decolorize the dye efficiently at pHs ranging from 4.0 to 9.0, and the optimal pH and temperature were pH 7.0 and 28 degrees C. A decolorization efficiency of approximately 90% was achieved by cultivation for 7 d at an initial dye concentration of 80 mg l(-1). The adsorption of the dye by cells was observed at the beginning of the decolorization, then the color became faint and finally disappeared when bilirubin oxidase (BOX) was released by the strain. Additionally, the visual observation and ultraviolet- visible (UV-VIS) spectral analysis demonstrated that decolorization involved biosorption and biodegradation. Native polyacrylamide gel electrophoresis of crude enzyme and purified BOX confirmed that BOX, which is an important extracellular oxidoreductase, played a major role in decolorization. Furthermore, purified BOX was demonstrated to degrade RBBR and other dyes by in vitro enzymatic experiments. Our results suggest that both the strain and its extracellular BOX have promising applications in dye effluent decolorization.

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

    Science.gov (United States)

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

    2015-03-01

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

  10. An ethanol/O{sub 2} biofuel cell based on an electropolymerized bilirubin oxidase/Pt nanoparticle bioelectrocatalytic O{sub 2}-reduction cathode

    Energy Technology Data Exchange (ETDEWEB)

    Yan, Yi-Ming; Baravik, Ilina; Tel-Vered, Ran; Willner, Itamar [Institute of Chemistry, Hebrew University of Jerusalem (Israel)

    2009-11-13

    An effective O{sub 2}-reducing bioelectrocatalytic electrode is prepared by the electrochemical crosslinking of thioaniline-modified Pt nanoparticles (NPs) and thioaniline-functionalized bilirubin oxidase (BOD). An O{sub 2}/ethanol biofuel cell element is constructed by integrating the Pt NP/BOD cathode and an electrically contacted alcohol dehydrogenase (AlcDH)-based anode. (Abstract Copyright [2009], Wiley Periodicals, Inc.)

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

    Science.gov (United States)

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

    2015-01-01

    OBJECTIVE The objective of this study was to evaluate the effect of phenobarbital and phototherapy combination on the total serum bilirubin of the newborn infants with isoimmune hemolytic disease (IHD) and its impact on blood exchange transfusion rates. PATIENTS AND METHOD This single-blinded, prospective, randomized, controlled trial was conducted between March 2013 and December 2014 at the pediatric ward of two Military Hospitals in Jordan. A total of 200 full-term neonates with IHD were divided randomly into two groups: (1) the phenobarbital plus phototherapy group (n = 103), and (2) the phototherapy-only group (n = 97). Infants in group 1 received an oral dose of 2.5 mg/kg phenobarbital every 12 hours for 3 days in addition to phototherapy. The total serum bilirubin was observed. RESULTS Of the total 200 included newborn infants, 186 infants completed the study: 97 infants were included in group 1 and 89 infants in group 2. The difference between the mean total serum bilirubin levels at 24, 48, and 72 hours after starting the trial was clinically and statistically significant at P < 0.05. The differences between the two groups were also statistically significant at P < 0.05. Of the total 186 who completed the study, only 22 underwent blood exchange transfusion [7 from group 1, and 15 from group 2 (P = 0.0478)]. CONCLUSION In a limited-resources setting, phenobarbital in combination with phototherapy may be helpful to newborn infants with IHD, as it results in a faster decline in total serum bilirubin, thus decreasing the need for blood exchange transfusion than phototherapy alone. PMID:26309423

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

    DEFF Research Database (Denmark)

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

    2009-01-01

    Low levels of bilirubin are associated with an increased risk of cardiovascular adverse events. Weight reduction is known to reduce several cardiovascular risk factors, but effects on bilirubin levels have not been reported. We studied the response of weight loss therapy with sibutramine...... and lifestyle change on levels of total bilirubin in an overweight or obese, cardiovascular high-risk population. Data from the first 4 weeks of the lead-in period of the Sibutramine Cardiovascular Outcome study were analyzed. A total of 10 198 patients provided body weight measurements before and after 4 weeks......, respectively. At screening, bilirubin concentrations were similar between weight loss groups (around 11 micromol/L, P = .7) and increased linearly as a function of weight loss. The effect was significantly more pronounced in men compared with women (P for interaction = .003). Adjusted for multiple variables...

  13. 原发性肝癌切除术后高胆红素血症临床分析%Clinical investigation on postoperative high serum bilirubin in patients with primary liver cancer after resection

    Institute of Scientific and Technical Information of China (English)

    黄涛; 周进学; 杨楠木; 宫东伟

    2011-01-01

    目的 探讨原发性肝癌切除术后胆红素变化的规律及导致高胆红素血症的临床因素.方法 回顾性分析97例原发性肝癌切除术患者临床资料,根据术后血清总胆红素水平分为高胆红素组和胆红素正常组,观察术后胆红素变化特点,分析导致术后高胆红素血症的临床因素.结果 红素正常组术后血清总胆红素4 d达峰值[(21.5±9.2)μmol/L],术后14 d可降至正常水平;高胆红素血症组血清总胆红素7 d达峰值[(49.2±25.4)μmol/L],术后14 d仍高于正常值2倍[(36.1 ±17.6)μmol/L].单因素Logistic分析显示:术前胆红素水平,肝功能Child分级,术中肝血流阻断方式,出血量,输血情况以及术后合并低钠血症与术后高胆红素血症有关;多因素Logistic回归分析结果 表明术前胆红素水平是原发性肝癌切除术后高胆红素血症独立预测指标(OR=5.406,χ2=11.319,P=0.001).结论 原发性肝癌切除术后动态监测血清胆红素水平是重要的.围手术期对发生商胆红素血症的相关临床因素积极防范并处理,可降低肝癌切除术后并发症发生率.%Objective To investigate the features of postoperative serum bilirubin changes and the clinical factors associated with high serum bilirubin level in patients with primary liver cancer after resection. Methods The clinical data of 97 patients with primary liver cancer who underwent hepatectomy were analysed retrospectively. The cases were divided into two groups: high serum bilirubin group and normal bilirubin group, respectively, according to serum bilirubin level during two weeks after operation. The features of postoperative serum bilirubin changes and the causitive factors of postoperative high serum bilirubin were analyzed. Results The postoperative serum bilirubin reached the peak value [ (21. 5 ± 9.2 )μmol/L ] on d4, and then decreased to normal on d 14 in normal bilirubin group. But in high serum bilirubin group the postoperative serum

  14. Research on Fetal Bilirubin Metabolism and the Relationship Between It and Fetal Outcome%胎儿胆红素代谢及其与胎儿结局的关系

    Institute of Scientific and Technical Information of China (English)

    王晓璐

    2011-01-01

    胆红素代谢对人体有重要作用,游离型胆红素可自由穿过脂膜和血脑屏障等,产生细胞毒性而引发新生儿核黄疸.胎儿胆红素代谢与成人不同,胎儿期肝脏尚未发育成熟,其体内只有少量胆红素可经肝脏转化为无毒的结合型胆红素,大部分是非结合型胆红素以胆红素-白蛋白复合物的形式溶于血浆中,通过胎盘上的胆红素转运载体运送至母体代谢.当胎儿体内胆红素浓度过高或白蛋白浓度降低等病理情况下,胆红素可从白蛋白结合位点上解离成为游离型胆红素,其可对胎儿产生神经毒性作用,造成胎儿不良结局.%Bilirubin metabolism plays an important role for the human,free bilirubin can pass through cell membranes, blood-brain barrier and lipid membranes freely, resulting in cell toxicity and neonatal kernicterus.Fetal bilirubin metabolism is different from the adults'. Because of the immaturity of fetal liver function, only a small amount of fetal bilirubin can be transformed into non-toxic conjugated bilirubin via fetal liver, while most of the unconjugated bilirubin dissolved in the plasma in the form of bilirubin-albumin complex is transferred to mother to be metabolized by bilirubin carriers in the placenta. In certain pathological conditions, such as high concentration of bilirubin or low concentration of albumin, bilirubin-albumin complex may be dissociated from albumin binding sites to free bilirubin, which can result in neurotoxic effects on fetus, causing fetal adverse outcomes.

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

    Science.gov (United States)

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

    2014-10-31

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-07-18

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

  17. Bilirubin inhibits the up-regulation of inducible nitric oxide synthase by scavenging reactive oxygen species generated by the toll-like receptor 4-dependent activation of NADPH oxidase.

    Science.gov (United States)

    Idelman, Gila; Smith, Darcey L H; Zucker, Stephen D

    2015-08-01

    It has been previously shown that bilirubin prevents the up-regulation of inducible nitric oxide synthase (iNOS) in response to LPS. The present study examines whether this effect is exerted through modulation of Toll-Like Receptor-4 (TLR4) signaling. LPS-stimulated iNOS and NADPH oxidase (Nox) activity in RAW 264.7 murine macrophages was assessed by measuring cellular nitrate and superoxide ( [Formula: see text] ) production, respectively. The generation of both nitrate and [Formula: see text] in response to LPS was suppressed by TLR4 inhibitors, indicating that activation of iNOS and Nox is TLR4-dependent. While treatment with superoxide dismutase (SOD) and bilirubin effectively abolished LPS-mediated [Formula: see text] production, hydrogen peroxide and nitrate release were inhibited by bilirubin and PEG-catalase, but not SOD, supporting that iNOS activation is primarily dependent upon intracellular H2O2. LPS treatment increased nuclear translocation of the redox-sensitive transcription factor Hypoxia Inducible Factor-1α (HIF-1α), an effect that was abolished by bilirubin. Cells transfected with murine iNOS reporter constructs in which the HIF-1α-specific hypoxia response element was disrupted exhibited a blunted response to LPS, supporting that HIF-1α mediates Nox-dependent iNOS expression. Bilirubin, but not SOD, blocked the cellular production of interferon-β, while interleukin-6 production remained unaffected. These data support that bilirubin inhibits the TLR4-mediated up-regulation of iNOS by preventing activation of HIF-1α through scavenging of Nox-derived reactive oxygen species. Bilirubin also suppresses interferon-β release via a ROS-independent mechanism. These findings characterize potential mechanisms for the anti-inflammatory effects of bilirubin.

  18. 新生儿经皮胆红素与血清胆红素测定影响因素及高胆红素血症感染的临床分析%Factors influencing determination of neonatal transcutaneous bilirubin and serum bilirubin and clinical analysis of hyperbilirubinemia

    Institute of Scientific and Technical Information of China (English)

    金霆; 费政芳; 严争

    2013-01-01

    OBJECTIVE To explore the related factors influencing the determination of the neonatal transcutaneous bilirubin and serum bilirubin and to analyze the causes of the neonatal infection hyperbilirubinemia. METHODS The transcutaneous bilirubin value in 250 children with hyperbilirubinemia and the bilirubin value of the bypass peripheral blood and serum bilirubin value were compared and analyzed, then the predisposing factors were analyzed. RESULTS The determination values of the transcutaneous bilirubin, peripheral blood bilirubin, and total serum bilirubin were(145.6±23. 5)mol/L, (148.3±20. l)mol/L, and (155. 2±15. 2) μmol/L, respectively, the differences were statistically significant(P<0. 001 ). There were 107 (42. 8%) cases of neonates who caught the neonatal hyperbilirubinemia primarily due to the perinatal factors, 81 (32. 4%) cases due to the infection factors. The infection factors mainly consisted of omphalitis, impetigo, septicemia, pneumonia, purulent meningitis, toxoplas-mosis infection, giant CMV infection, and congenital syphilis. CONCLUSION The determination of transcutaneous bilirubin is highly correlated with the level of serum bilirubin. The infection factors take a secondary place to cause the hyperbilirubinemia, the treatment should be conducted according to the specific cause by taking different treatment programs.%目的 探讨新生儿经皮胆红素与血清胆红素测定的影响因素及高胆红素血症感染因素的临床分析.方法 对发生胆红素血症250例患儿经皮胆红素值与经末梢血和血清测定的总胆红素值进行对照,同时对患儿的发病因素进行分析.结果 婴儿经皮胆红素与末梢血胆红素以及血清总胆红素测定值分别为(145.6±23.5)、(148.3±20.1)、(155.2±15.2)μmol/L,差异有统计学意义(P<0.01);导致新生儿高胆红素血症的最主要因素为围产因素107例,占42.8%,感染因素81例,占32.4%,感染因素主要包括脐炎、脓疱疹、败血症

  19. Exposure to secondhand smoke and cognitive impairment in non-smokers: national cross sectional study with cotinine measurement%非吸烟者被动吸烟与认知损害:可替宁检测的全国横断面研究

    Institute of Scientific and Technical Information of China (English)

    David J Llewellyn; Iain A Lang; Kenneth M Langa; Felix Naughton; Fiona E Matthews; 彭晶晶

    2009-01-01

    Objective To examine the association between a biomarker of exposure to secondhand smoke ( salivary cotinine concentration) and cognitive impairment. Design Cross sectional analysis of a national population based study. Setting Stratified random sample of households throughout England. Participants 4809 non-smoking adults aged 50 years or more from the 1998, 1999, and 2001 waves of the Health Survey for England who also participated in the 2002 wave of the English Longitudinal Study of Ageing and provided saliva samples for cotinine assay and a detailed smoking history. Main outcome measure Cognitive impairment as defined by the lowest 10% of scores on a battery of neuropsychological tests. Results Participants who did not smoke, use nicotine products, or have salivary cotinine concentrations of 14. 1 ng/ml or more were divided into four equal size groups on the basis of cotinine concentrations. Compared with the lowest fourth of cotinine concentration (0. 0-0. 1 ng/ml) the odds ratios (95% confidenco intervals) for cognitive impairment in the second (0.2-0.3 ng/ml), third (0.4-0.7 ng/ml), and highest fourths (0. 8-13. 5 ng/ml ) were 1.08 (0.78 to 1.48), 1. 13 (0.81 to 1.56), and 1.44 (1.07 to 1.94; P for trend 0. 02), after adjustment for a wide range of established risk factors for cognitive impairment. A similar pattern of associations was observed for never smokers and former smokers. Conclusions Exposure to secondhand smoke may be associated with increased odds of cognitive impairment. Prospective nationally representative studies relating biomarkers of exposure to cognitive decline and risk of dementia are needed.%目的 检测被动吸烟者的生物标记物(唾液可替宁浓度)与认知损害的关系.设计基于全国人口横断面分析的研究.样本全英格兰家庭的分层随机样本.参与者年龄≥50岁非吸烟的成年人4809例.他们来源于参加1998、1999和2001年英格兰健康调查且再次参加2002年英国人口老龄化纵

  20. Study on the quality control of bilirubin in self-made serum%自制血清总胆红素质控品研究

    Institute of Scientific and Technical Information of China (English)

    牟虹; 李强

    2009-01-01

    目的 自制胆红素室内质控品作为测定总胆红素(TBIL)参比血清,评价自制室内质控品是否符合临床要求,降低检验成本.方法 收集日常工作中TBIL高、中、低值标本分别混合后分装并加入赋形剂,经低温干燥至干粉,低温避光冷藏,即为自制质控品.结果 自制室内质控品在26 d内与新鲜混合血清的TBIL比较,差异无统计学意义(P>0.05).结论 自制TBIL室内质控品符合室内质控要求,该分装方法用于自制室内质控品,可降低检验成本.%Objective Using bilirubin self-made laboratory quality control of products as a total bilirubin (TB) Reference Serum to evaluate the self-made laboratory quality control about whether to fit the clinical requirements and to reduce the cost of testing.Methods Collect the high,medium,low and mixed loaded total bilirubin(TB) respectively at the routine working days, and then add some excipients and put it in the place under low temperature till dry powder, which should be stored in cold 、dark and frozen environment.Results Within 26 days, compared the self-made laboratory quality control products(frozen mixed serum) with the fresh mixed blood plasma total bilirubin (TB),the difference was not significant (P> 0.05).Conclusion Total bilirubin self-made laboratory quality control of products meet with the requirements, so this sub-loaded method can be used for quality control laboratory of self-made products, and reduce testing costs.

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

    Science.gov (United States)

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

    2015-11-17

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2004-10-06

    A dinucleotide repeat polymorphism (5-, 6-, 7-, or 8-TA units) has been identified within the promoter region of UDP-glucuronosyltransferase 1A1 gene (UGT1A1). The 7-TA repeat allele has been associated with elevated serum bilirubin levels that cause a mild hyperbilirubinemia (Gilbert's syndrome). Studies suggest that promoter transcriptional activity of UGT1A1 is inversely related to the number of TA repeats and that unconjugated bilirubin concentration increases directly with the number of TA repeat elements. Because bilirubin is a known antioxidant, we hypothesized that UGT1A1 repeats associated with higher bilirubin may be protective against oxidative damage. We examined the effect of UGT1A1 genotype on