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

    Directory of Open Access Journals (Sweden)

    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. Bilirubin Test

    Science.gov (United States)

    ... Bilirubin; Indirect Bilirubin; Unconjugated Bilirubin Formal name: Bilirubin - blood Related tests: Liver Panel ; GGT ; ALP ; AST ; ALT ; Hepatitis A ; Hepatitis B ; Hepatitis C ; Complete Blood Count ; Urinalysis ; Direct Antiglobulin ...

  3. Modeling Impaired Hippocampal Neurogenesis after Radiation Exposure.

    Science.gov (United States)

    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. PMID:26943452

  4. [Cytoprotective effects of bilirubin].

    Science.gov (United States)

    Vítek, L

    2005-01-01

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

  5. Blood Test: Bilirubin

    Science.gov (United States)

    ... the blood. Babies with high levels may need phototherapy (treatment with a special light that makes bilirubin ... are afraid of needles. Explaining the test in terms your child can understand might help ease some ...

  6. Acr ylamide exposure impairs blood-cerebrospinal lfuid barrier function

    Institute of Scientific and Technical Information of China (English)

    Xue Yao; Licheng Yan; Lin Yao; Weijun Guan; Fanxu Zeng; Fuyuan Cao; Yanshu Zhang

    2014-01-01

    Previous studies show that chronic acrylamide exposure leads to central and peripheral neu-ropathy. However, the underlying mechanisms remained unclear. In this study, we examined the permeability of the blood-cerebrospinal lfuid barrier, and its ability to secrete transthyretin and transport leptin of rats exposed to acrylamide for 7, 14, 21 or 28 days. Transthyretin levels in cerebrospinal lfuid began to decline on day 7 after acrylamide exposure. The sodium lfuorescein level in cerebrospinal lfuid was increased on day 14 after exposure. Evans blue concentration in cerebrospinal lfuid was increased and the cerebrospinal lfuid/serum leptin ratio was decreased on days 21 and 28 after exposure. In comparison, the cerebrospinal lfuid/serum albumin ratio was increased on day 28 after exposure. Our ifndings show that acrylamide exposure damages the blood-cerebrospinal lfuid barrier and impairs secretory and transport functions. These changes may underlie acrylamide-induced neurotoxicity.

  7. Acrylamide exposure impairs blood-cerebrospinal fluid barrier function.

    Science.gov (United States)

    Yao, Xue; Yan, Licheng; Yao, Lin; Guan, Weijun; Zeng, Fanxu; Cao, Fuyuan; Zhang, Yanshu

    2014-03-01

    Previous studies show that chronic acrylamide exposure leads to central and peripheral neu-ropathy. However, the underlying mechanisms remained unclear. In this study, we examined the permeability of the blood-cerebrospinal fluid barrier, and its ability to secrete transthyretin and transport leptin of rats exposed to acrylamide for 7, 14, 21 or 28 days. Transthyretin levels in cerebrospinal fluid began to decline on day 7 after acrylamide exposure. The sodium fluorescein level in cerebrospinal fluid was increased on day 14 after exposure. Evans blue concentration in cerebrospinal fluid was increased and the cerebrospinal fluid/serum leptin ratio was decreased on days 21 and 28 after exposure. In comparison, the cerebrospinal fluid/serum albumin ratio was increased on day 28 after exposure. Our findings show that acrylamide exposure damages the blood-cerebrospinal fluid barrier and impairs secretory and transport functions. These changes may underlie acrylamide-induced neurotoxicity. PMID:25206854

  8. Atazanavir–bilirubin interaction: a pharmacokinetic–pharmacodynamic model

    Directory of Open Access Journals (Sweden)

    Lozano R

    2013-09-01

    Full Text Available Roberto Lozano,1 Nieves Domeque,2 Alberto-Fermin Apesteguia3 1Pharmacy Department, 2Psychiatry Department, Hospital Real Nuestra Señora de Gracia, 3Pharmacy Department, Hospital Clinico Universitario "Lozano Blesa", Zaragoza, Spain Purpose: The aim of this work was to analyze the atazanavir–bilirubin relationship, using a new mathematical approach to pharmacokinetic–pharmacodynamic models, for competitive drug interactions based on Michaelis–Menten equations. Patients and methods: Because atazanavir induces an increase of plasma bilirubin levels, in a concentration-dependent manner, we developed a mathematical model, based on increments of atazanavir and bilirubin concentrations at steady state, in HIV infected (HIV+ patients, and plotted the corresponding nomogram for detecting suboptimal atazanavir exposure. Results: By applying the obtained model, the results indicate that an absolute value or an increment of bilirubin at steady state below 3.8 µmol/L, are predictive of suboptimal atazanavir exposure and therapeutic failure. Conclusion: We have successfully implemented a new mathematical approach to pharmacokinetic–pharmacodynamic model for atazanavir–bilirubin interaction. As a result, we found that bilirubin plasma levels constitute a good marker of exposure to atazanavir and of viral suppression. Keywords: atazanavir, bilirubin, HIV/AIDS, pharmacodynamics, pharmacokinetics

  9. Bilirubin present in diverse angiosperms

    OpenAIRE

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

    2010-01-01

    Background and aims Bilirubin is an orange-yellow tetrapyrrole produced from the breakdown of heme by mammals and some other vertebrates. Plants, algae and cyanobacteria synthesize molecules similar to bilirubin, including the protein-bound bilins and phytochromobilin which harvest or sense light. Recently, we discovered bilirubin in the arils of Strelitzia nicolai, the White Bird of Paradise Tree, which was the first example of this molecule in a higher plant. Subsequently, we identified bil...

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

    Directory of Open Access Journals (Sweden)

    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.

  11. 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.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

  14. 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.

  15. 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%.

  16. A novel predictor of infarct-related artery patency before percutaneous intervention and in-hospital outcomes for ST-segment elevation myocardial infarction patients: serum bilirubin level

    OpenAIRE

    Acet, Halit; Ertş, Faruk; Akıl, Mehmet Ata; Polat, Nihat; Aydın, Mesut; Akyüz, Abdurrahman; Ayçiçek, Hilal; Alan, Sait

    2014-01-01

    Introduction Previous studies have reported a relationship between serum bilirubin levels and coronary artery disease (CAD). However, data are rare up to now regarding the relation of bilirubin levels with infarct-related artery (IRA) patency in the setting of ST-segment elevation myocardial infarction (STEMI). Moreover, previous studies reported that increased bilirubin was related to impaired post-intervention coronary flow. To our knowledge, the association between serum total bilirubin (T...

  17. Impaired Odor Identification in Children with Histories of Heavy Prenatal Alcohol Exposure

    OpenAIRE

    Bower, Emily; Szajer, Jacquelyn; Mattson, Sarah N.; Riley, Edward P.; Murphy, Claire

    2013-01-01

    Prenatal alcohol exposure can lead to behavioral and cognitive impairments across multiple domains. Many of the brain regions impacted by prenatal alcohol exposure are also linked with olfactory processing, and odor identification deficits have been documented in certain neurological disorders associated with these brain regions. As odor identification following prenatal alcohol exposure is not well studied, we compared odor identification in children with prenatal exposure to alcohol (AE) to...

  18. Taurine improves the spatial learning and memory ability impaired by sub-chronic manganese exposure

    OpenAIRE

    Lu, Cai-Ling; Tang, Shen; Meng, Zhi-Juan; He, Yi-Yuan; Song, Ling-Yong; Liu, Yin-Pin; Ma, Ning; Li, Xi-Yi; Guo, Song-Chao

    2014-01-01

    Background Excessive manganese exposure induced cognitive deficit. Several lines of evidence have demonstrated that taurine improves cognitive impairment induced by numerous neurotoxins. However, the role of taurine on manganese-induced damages in learning and memory is still elusive. This goal of this study was to investigate the beneficial effect of taurine on learning and memory capacity impairment by manganese exposure in an animal model. Results The escape latency in the Morris Water Maz...

  19. Acrylamide exposure impairs blood-cerebrospinal fluid barrier function

    OpenAIRE

    Yao, Xue; Yan, Licheng; Yao, Lin; GUAN, Weijun; Zeng, Fanxu; Cao, Fuyuan; Zhang, Yanshu

    2014-01-01

    Previous studies show that chronic acrylamide exposure leads to central and peripheral neu-ropathy. However, the underlying mechanisms remained unclear. In this study, we examined the permeability of the blood-cerebrospinal fluid barrier, and its ability to secrete transthyretin and transport leptin of rats exposed to acrylamide for 7, 14, 21 or 28 days. Transthyretin levels in cerebrospinal fluid began to decline on day 7 after acrylamide exposure. The sodium fluorescein level in cerebrospin...

  20. Impaired vascular function after exposure to diesel exhaust generated at urban transient running conditions

    OpenAIRE

    Westerholm Roger; Boman Christoffer; Söderberg Stefan; Langrish Jeremy P; Lucking Andrew J; Törnqvist Håkan; Lundbäck Magnus; Mills Nicholas L; Barath Stefan; Löndahl Jakob; Donaldson Ken; Mudway Ian S; Sandström Thomas; Newby David E; Blomberg Anders

    2010-01-01

    Abstract Background Traffic emissions including diesel engine exhaust are associated with increased respiratory and cardiovascular morbidity and mortality. Controlled human exposure studies have demonstrated impaired vascular function after inhalation of exhaust generated by a diesel engine under idling conditions. Objectives To assess the vascular and fibrinolytic effects of exposure to diesel exhaust generated during urban-cycle running conditions that mimic ambient 'real-world' exposures. ...

  1. Bilirubin Neurotoxicity in Preterm Infants: Risk and Prevention

    OpenAIRE

    Bhutani, Vinod K.; Wong, Ronald J

    2013-01-01

    Hemolytic conditions in preterm neonates, including Rhesus (Rh) disease, can lead to mortality and long-term impairments due to bilirubin neurotoxicity. Universal access to Rh immunoprophylaxis, coordinated perinatal-neonatal care, and effective phototherapy has virtually eliminated the risk of kernicterus in many countries. In the absence of jaundice due to isoimmunization and without access to phototherapy or exchange transfusion (in 1955), kernicterus was reported at 10.1%, 5.5%, and 1.2% ...

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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 nicotine exposure. RGZ improved mitochondrial function through tighter coupling of oxidative phosphorylation. PMID:26899624

  4. Impairment induced by chronic occupational cadmium exposure during brazing process

    International Nuclear Information System (INIS)

    Cadmium (CD) is considered a metal of the 20th century to which all inhabitants of develop societies are exposed. Long-term occupational and environmental exposure to CD often results in renal dysfunction as the kidney is considered the critical target organ. The aim of this work was to evalutate both resporatory and renal manifestations induced by occupational exposure to CD compounds during brazing process, and suggesting a protocol for prevention and control for CD- induced health effects. This study was conducted on 20 males occupationally exposed workers. They are divided into two groups: Group-1 included (10) exposed smokers and group-2 included (10) exposed non-smokers. Results of both groups were compared with those of 10 healthy age and sex matched non-smokers. All subjects were subjected to detailed history taking and laboratory investigations including blood and urinary CD, liver profile (SGOT, SGPT and alkline phosphates), kindey function tests (blood urea, creatinine and urinary beta2- microglobulin). The level of Cd in the atmosphere of the work plase air was also assessed to detect the degree of exposure as it was about 6 times greater than thesave level (1 mu /m3).(1) This study demonstrated elevation levels of blood CD, urea, creatinine and urinary CD and beta2 -microglobulin for both exposed worker groups than the controls. In additions no appreciable were noted for liver function tests, although the levels fell within normal range

  5. 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. PMID:27071062

  6. 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 (pbenefits to mental health, recorded after exercise, were absent after AG, indicating that AG might cause neurocognitive deconditioning. PMID:24184512

  7. Juvenile exposure to vinclozolin shifts sex ratios and impairs reproductive capacity of zebrafish.

    Science.gov (United States)

    Lor, Yer; Revak, Andrew; Weigand, Jenna; Hicks, Elisabeth; Howard, David R; King-Heiden, Tisha C

    2015-12-01

    Exposure to endocrine disruptors during critical periods of development can impact the sustainability of wild fish populations. Anti-androgenic compounds have received less attention, but are capable of modulating gonad differentiation and maturation, and impairing reproduction in fish. The fungicide vinclozolin (VZ) has been shown to impair reproduction in adult fish, but less is known about its effects following exposure earlier in development. Here we show that waterborne exposure to 400μg VZ/L during critical periods of sex differentiation (21-35 days post fertilization) permanently shifts sex ratios towards females, and alters the maturation of the gonad. Both fecundity and fertility were reduced, even when oogenesis and spermatogenesis recover and sperm motility is not altered. These results demonstrate the need to better understand the impacts of early exposure to anti-androgenic compounds on fish. PMID:26423773

  8. 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. PMID:27102012

  9. Developmental ethanol exposure-induced sleep fragmentation predicts adult cognitive impairment.

    Science.gov (United States)

    Wilson, D A; Masiello, K; Lewin, M P; Hui, M; Smiley, J F; Saito, M

    2016-05-13

    Developmental ethanol (EtOH) exposure can lead to long-lasting cognitive impairment, hyperactivity, and emotional dysregulation among other problems. In healthy adults, sleep plays an important role in each of these behavioral manifestations. Here we explored circadian rhythms (activity, temperature) and slow-wave sleep (SWS) in adult mice that had received a single day of EtOH exposure on postnatal day 7 and saline littermate controls. We tested for correlations between slow-wave activity and both contextual fear conditioning and hyperactivity. Developmental EtOH resulted in adult hyperactivity within the home cage compared to controls but did not significantly modify circadian cycles in activity or temperature. It also resulted in reduced and fragmented SWS, including reduced slow-wave bout duration and increased slow-wave/fast-wave transitions over 24-h periods. In the same animals, developmental EtOH exposure also resulted in impaired contextual fear conditioning memory. The impairment in memory was significantly correlated with SWS fragmentation. Furthermore, EtOH-treated animals did not display a post-training modification in SWS which occurred in controls. In contrast to the memory impairment, sleep fragmentation was not correlated with the developmental EtOH-induced hyperactivity. Together these results suggest that disruption of SWS and its plasticity are a secondary contributor to a subset of developmental EtOH exposure's long-lasting consequences. PMID:26892295

  10. 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…

  11. 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…

  12. A NOVEL EFFECT OF DIOXIN: EXPOSURE DURING PREGNANCY SEVERELY IMPAIRS MAMMARY GLAND DIFFERENTIATION

    Science.gov (United States)

    A novel effect of dioxin: Exposure during pregnancy severely impairs mammary gland differentiation.Beth A. Vorderstrasse1, Suzanne E. Fenton2, Andrea A. Bohn3, Jennifer A. Cundiff1, and B. Paige Lawrence1,3,4 1Department of Pharmaceutical Sciences, Washington State Universi...

  13. Impaired vascular function after exposure to diesel exhaust generated at urban transient running conditions

    Directory of Open Access Journals (Sweden)

    Westerholm Roger

    2010-07-01

    Full Text Available Abstract Background Traffic emissions including diesel engine exhaust are associated with increased respiratory and cardiovascular morbidity and mortality. Controlled human exposure studies have demonstrated impaired vascular function after inhalation of exhaust generated by a diesel engine under idling conditions. Objectives To assess the vascular and fibrinolytic effects of exposure to diesel exhaust generated during urban-cycle running conditions that mimic ambient 'real-world' exposures. Methods In a randomised double-blind crossover study, eighteen healthy male volunteers were exposed to diesel exhaust (approximately 250 μg/m3 or filtered air for one hour during intermittent exercise. Diesel exhaust was generated during the urban part of the standardized European Transient Cycle. Six hours post-exposure, vascular vasomotor and fibrinolytic function was assessed during venous occlusion plethysmography with intra-arterial agonist infusions. Measurements and Main Results Forearm blood flow increased in a dose-dependent manner with both endothelial-dependent (acetylcholine and bradykinin and endothelial-independent (sodium nitroprusside and verapamil vasodilators. Diesel exhaust exposure attenuated the vasodilatation to acetylcholine (P Conclusion Exposure to diesel exhaust generated under transient running conditions, as a relevant model of urban air pollution, impairs vasomotor function and endogenous fibrinolysis in a similar way as exposure to diesel exhaust generated at idling. This indicates that adverse vascular effects of diesel exhaust inhalation occur over different running conditions with varying exhaust composition and concentrations as well as physicochemical particle properties. Importantly, exposure to diesel exhaust under ETC conditions was also associated with a novel finding of impaired of calcium channel-dependent vasomotor function. This implies that certain cardiovascular endpoints seem to be related to general diesel

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

    Science.gov (United States)

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

    1992-05-01

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

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

    Directory of Open Access Journals (Sweden)

    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.

  16. A transcriptome analysis identifies molecular effectors of unconjugated bilirubin in human neuroblastoma SH-SY5Y cells

    Directory of Open Access Journals (Sweden)

    Giraudi Pablo

    2009-11-01

    Full Text Available Abstract Background The deposition of unconjugated bilirubin (UCB in selected regions of the brain results in irreversible neuronal damage, or Bilirubin Encephalopathy (BE. Although UCB impairs a large number of cellular functions in other tissues, the basic mechanisms of neurotoxicity have not yet been fully clarified. While cells can accumulate UCB by passive diffusion, cell protection may involve multiple mechanisms including the extrusion of the pigment as well as pro-survival homeostatic responses that are still unknown. Results Transcriptome changes induced by UCB exposure in SH-SY5Y neuroblastoma cell line were examined by high density oligonucleotide microarrays. Two-hundred and thirty genes were induced after 24 hours. A Gene Ontology (GO analysis showed that at least 50 genes were directly involved in the endoplasmic reticulum (ER stress response. Validation of selected ER stress genes is shown by quantitative RT-PCR. Analysis of XBP1 splicing and DDIT3/CHOP subcellular localization is presented. Conclusion These results show for the first time that UCB exposure induces ER stress response as major intracellular homeostasis in surviving neuroblastoma cells in vitro.

  17. 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.

  18. Brief postnatal exposure to phenobarbital impairs passive avoidance learning and sensorimotor gating in rats.

    Science.gov (United States)

    Gutherz, Samuel B; Kulick, Catherine V; Soper, Colin; Kondratyev, Alexei; Gale, Karen; Forcelli, Patrick A

    2014-08-01

    Phenobarbital is the most commonly utilized drug for the treatment of neonatal seizures. However, mounting preclinical evidence suggests that even brief exposure to phenobarbital in the neonatal period can induce neuronal apoptosis, alterations in synaptic development, and long-lasting changes in behavioral functions. In the present report, we treated neonatal rat pups with phenobarbital and evaluated behavior in adulthood. Pups were treated initially with a loading dose (80 mg/kg) on postnatal day (P)7 and with a lower dose (40 mg/kg) on P8 and P9. We examined sensorimotor gating (prepulse inhibition), passive avoidance, and conditioned place preference for cocaine when the animals reached adulthood. Consistent with our previous reports, we found that three days of neonatal exposure to phenobarbital significantly impaired prepulse inhibition compared with vehicle-exposed control animals. Using a step-though passive avoidance paradigm, we found that animals exposed to phenobarbital as neonates and tested as adults showed significant deficits in passive avoidance retention compared with matched controls, indicating impairment in associative memory and/or recall. Finally, we examined place preference conditioning in response to cocaine. Phenobarbital exposure did not alter the normal conditioned place preference associated with cocaine exposure. Our findings expand the profile of behavioral toxicity induced by phenobarbital. PMID:25112558

  19. Multistimuli-Responsive Bilirubin Nanoparticles for Anticancer Therapy.

    Science.gov (United States)

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

    2016-08-26

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

  20. Animal pigment bilirubin discovered in plants.

    Science.gov (United States)

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

    2009-03-01

    The bile pigment bilirubin-IXalpha is the degradative product of heme, distributed among mammals and some other vertebrates. It can be recognized as the pigment responsible for the yellow color of jaundice and healing bruises. In this paper we present the first example of the isolation of bilirubin in plants. The compound was isolated from the brilliant orange-colored arils of Strelitzia nicolai, the white bird of paradise tree, and characterized by HPLC-ESMS, UV-visible, (1)H NMR, and (13)C NMR spectroscopy, as well as comparison with an authentic standard. This discovery indicates that plant cyclic tetrapyrroles may undergo degradation by a previously unknown pathway. Preliminary analyses of related plants, including S. reginae, the bird of paradise, also revealed bilirubin in the arils and flowers, indicating that the occurrence of bilirubin is not limited to a single species or tissue type. PMID:19206232

  1. 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

    2015-01-01

    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. PMID:26568480

  2. Effect of recreational noise exposure on hearing impairment among teenage students.

    Science.gov (United States)

    Tung, Chen-Yin; Chao, Keh-Ping

    2013-01-01

    Several studies have focused on the potential impact of children's hearing loss on learning and development. Recently, numerous teenage students have been found to be fond of listening to music on personal devices and participating in recreational music activities. The objective of this study was to investigate teenage students' hearing impairment, their experience with recreational noise exposure, and their self-reported hearing. The participants were 1878 first-year students at a university in Taiwan. The result of the pure tone audiometry test showed that 11.9% of the participants had one or two ears with a hearing threshold over 25 dB. Over the past year, approximately 80.9% of the participants had taken part in at least one loud-noise recreational activity, and 90.9% of the participants were in the habit of using earphones. Among the participants, 190 students with a high level of recreational noise exposure were assigned to the exposure group, and 191 students with a low level of recreational noise exposure constituted the control group. The exposure group had more hearing problems than the control group, but no significant difference existed between the two groups in the pure tone audiometry test (p=0.857). It is suggested that the schools should reinforce hearing health education and proactively provide intervention measures, such as hearing tests, evaluation of noise exposure, and hearing protection. PMID:22940166

  3. 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.

  4. 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....

  5. PPARα: A Master Regulator of Bilirubin Homeostasis

    OpenAIRE

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

    2014-01-01

    Hypolipidemic fibrates activate the peroxisome proliferator-activated receptor (PPAR) α to modulate lipid oxidation and metabolism. The present study aimed at evaluating how 3 PPARα agonists, namely, fenofibrate, gemfibrozil, and Wy14,643, affect bilirubin synthesis and metabolism. Human umbilical vein epithelial cells (HUVEC) and coronary artery smooth muscle cells (CASMC) were cultured in the absence or presence of the 3 activators, and mRNA, protein, and/or activity levels of the bilirubin...

  6. 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. PMID:26834859

  7. 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.

  8. 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.

  9. Chronic exposure of juvenile rats to environmental noise impairs hippocampal cell proliferation in adulthood

    Directory of Open Access Journals (Sweden)

    Fernando Jáuregui-Huerta

    2011-01-01

    Full Text Available Increasing evidence indicates that chronic exposure to environmental noise may permanently affect the central nervous system. The aim of this study was to evaluate the long-term effects of early exposure to environmental noise on the hippocampal cell proliferation of the adult male rat. Early-weaned Wistar rats were exposed for 15 days to a rats′ audiogram-fitted adaptation to a noisy environment. Two months later, the rats were injected with the cellular proliferation marker 5΄bromodeoxiuridine (BrdU, and their brains were processed for immunohistochemical analysis. Coronal sections were immunolabeled with anti-BrdU antibodies to identify new-born cells in dentate gyrus (DG, cornu amonis areas CA1 and CA3. In addition, blood samples were obtained to evaluate corticosterone serum levels after noise exposure. All data are expressed as mean΁standard deviation. For mean comparisons between groups, we used the Student t test. We found an increase in corticosterone serum levels after environmental noise exposure. Interestingly, noise-exposed rats showed a long-term reduction of proliferating cells in the hippocampal formation, as compared to controls. These findings indicate that chronic environmental noise exposure at young ages produces persistent non-auditory impairment that modifies cell proliferation in the hippocampal formation.

  10. 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.

  11. PPARα: A Master Regulator of Bilirubin Homeostasis

    Directory of Open Access Journals (Sweden)

    Cyril Bigo

    2014-01-01

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

  12. 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.

  13. 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.

  14. 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

  15. 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.

  16. Initial photochemistry of bilirubin probed by femtosecond spectroscopy.

    Science.gov (United States)

    Zietz, Burkhard; Gillbro, Tomas

    2007-10-18

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

  17. Lead Exposure during Synaptogenesis Alters Vesicular Proteins and Impairs Vesicular Release: Potential Role of NMDA Receptor–Dependent BDNF Signaling

    OpenAIRE

    Neal, April P.; Stansfield, Kirstie H.; Worley, Paul F.; Thompson, Richard E.; Guilarte, Tomás R.

    2010-01-01

    Lead (Pb2+) exposure is known to affect presynaptic neurotransmitter release in both in vivo and cell culture models. However, the precise mechanism by which Pb2+ impairs neurotransmitter release remains unknown. In the current study, we show that Pb2+ exposure during synaptogenesis in cultured hippocampal neurons produces the loss of synaptophysin (Syn) and synaptobrevin (Syb), two proteins involved in vesicular release. Pb2+ exposure also increased the number of presynaptic contact sites. H...

  18. Prognostic significance of serum bilirubin in stroke

    International Nuclear Information System (INIS)

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

  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. 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.

  1. Acute and chronic metal exposure impairs locomotion activity in Drosophila melanogaster: a model to study Parkinsonism.

    Science.gov (United States)

    Bonilla-Ramirez, Leonardo; Jimenez-Del-Rio, Marlene; Velez-Pardo, Carlos

    2011-12-01

    The biometals iron (Fe), manganese (Mn) and copper (Cu) have been associated to Parkinson's disease (PD) and Parkinsonism. In this work, we report for the first time that acute (15 mM for up to 5 days) or chronic (0.5 mM for up to 15 days) Fe, Mn and Cu exposure significantly reduced life span and locomotor activity (i.e. climbing capabilities) in Drosophila melanogaster. It is shown that the concentration of those biometals dramatically increase in Drosophila's brain acutely or chronically fed with metal. We demonstrate that the metal accumulation in the fly's head is associated with the neurodegeneration of several dopaminergic neuronal clusters. Interestingly, it is found that the PPL2ab DAergic neuronal cluster was erode by the three metals in acute and chronic metal exposure and the PPL3 DAergic cluster was also erode by the three metals but in acute metal exposure only. Furthermore, we found that the chelator desferoxamine, ethylenediaminetetraacetic acid, and D: -penicillamine were able to protect but not rescue D. melanogaster against metal intoxication. Taken together these data suggest that iron, manganese and copper are capable to destroy DAergic neurons in the fly's brain, thereby impairing their movement capabilities. This work provides for the first time metal-induced Parkinson-like symptoms in D. melanogaster. Understanding therefore the effects of biometals in the Drosophila model may provide insights into the toxic effect of metal ions and more effective therapeutic approaches to Parkinsonism. PMID:21594680

  2. 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.

  3. Acute Acrolein Exposure Induces Impairment of Vocal Fold Epithelial Barrier Function.

    Science.gov (United States)

    Liu, Xinxin; Zheng, Wei; Sivasankar, M Preeti

    2016-01-01

    Acrolein is a ubiquitous pollutant abundant in cigarette smoke, mobile exhaust, and industrial waste. There is limited literature on the effects of acrolein on vocal fold tissue, although there are clinical reports of voice changes after pollutant exposures. Vocal folds are responsible for voice production. The overall objective of this study was to investigate the effects of acrolein exposure on viable, excised vocal fold epithelial tissue and to characterize the mechanism underlying acrolein toxicity. Vocal fold epithelia were studied because they form the outermost layer of the vocal folds and are a primary recipient of inhaled pollutants. Porcine vocal fold epithelia were exposed to 0, 50, 100, 500, 900 or 1300 μM of acrolein for 3 hours; the metabolic activity, epithelial resistance, epithelial permeability, tight junction protein (occludin and claudin 3) expression, cell membrane integrity and lipid peroxidation were investigated. The data demonstrated that acrolein exposure at 500 μM significantly reduced vocal fold epithelial metabolic activity by 27.2% (p≤0.001). Incubation with 100 μM acrolein caused a marked increase in epithelial permeability by 130.5% (presistance (TEER) by 180.0% (pchange in acrolein-treated samples, the cell membrane integrity was significantly damaged with a 45.6% increase of lipid peroxidation as compared to controls (p<0.05). Taken together, these data provide evidence that acute acrolein exposure impairs vocal fold epithelial barrier integrity. Lipid peroxidation-induced cell membrane damage may play an important role in reducing the barrier function of the epithelium. PMID:27643990

  4. Acute Acrolein Exposure Induces Impairment of Vocal Fold Epithelial Barrier Function

    Science.gov (United States)

    Zheng, Wei; Sivasankar, M. Preeti

    2016-01-01

    Acrolein is a ubiquitous pollutant abundant in cigarette smoke, mobile exhaust, and industrial waste. There is limited literature on the effects of acrolein on vocal fold tissue, although there are clinical reports of voice changes after pollutant exposures. Vocal folds are responsible for voice production. The overall objective of this study was to investigate the effects of acrolein exposure on viable, excised vocal fold epithelial tissue and to characterize the mechanism underlying acrolein toxicity. Vocal fold epithelia were studied because they form the outermost layer of the vocal folds and are a primary recipient of inhaled pollutants. Porcine vocal fold epithelia were exposed to 0, 50, 100, 500, 900 or 1300 μM of acrolein for 3 hours; the metabolic activity, epithelial resistance, epithelial permeability, tight junction protein (occludin and claudin 3) expression, cell membrane integrity and lipid peroxidation were investigated. The data demonstrated that acrolein exposure at 500 μM significantly reduced vocal fold epithelial metabolic activity by 27.2% (p≤0.001). Incubation with 100 μM acrolein caused a marked increase in epithelial permeability by 130.5% (presistance (TEER) by 180.0% (pchange in acrolein-treated samples, the cell membrane integrity was significantly damaged with a 45.6% increase of lipid peroxidation as compared to controls (p<0.05). Taken together, these data provide evidence that acute acrolein exposure impairs vocal fold epithelial barrier integrity. Lipid peroxidation-induced cell membrane damage may play an important role in reducing the barrier function of the epithelium. PMID:27643990

  5. 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

  6. Serum Bilirubin Levels and Developmental Outcome

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2006-05-01

    Full Text Available The neurodevlopmental risks associated with neonatal total serum bilirubin levels of 25 mg/dL or higher in 140 affected infants were compared with 419 randomly selected controls from a cohort of term-infants born 1995-1998 in Kaiser Permanente hospitals in northern California.

  7. Mechanisms of bilirubin toxicity: clinical implications.

    Science.gov (United States)

    Hansen, Thor Willy Ruud

    2002-12-01

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

  8. 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. PMID:27374426

  9. Impairment of mitochondrial energy metabolism of two marine fish by in vitro mercuric chloride exposure

    International Nuclear Information System (INIS)

    Highlights: • Hg levels usually found in contaminated environments may compromise fish metabolism. • Hg impairs both the oxidative phosphorylation and the electron transport chain. • The decrease of F1Fo-ATPase activity confirmed Hg inhibition of ADP phosphorylation. • The decrease of SDH activity supported Hg inhibition of the electron transport chain. • Mitochondrial respiration is a suitable biomarker of exposure to Hg. - Abstract: The goal of this work was to understand the extent of mercury toxic effects in liver metabolism under an episode of acute contamination. Hence, the effects of in vitro mercuric chloride in liver mitochondria were assessed in two commercial marine fish: Senegalese sole (Solea senegalensis) and gilthead seabream (Sparus aurata). Liver mitochondria were exposed to 0.2 mg L−1 of mercury, the average concentration found in fish inhabiting contaminated areas. Mercuric chloride depressed mitochondrial respiration state 3 and the maximal oxygen consumption in the presence of FCCP indicating inhibitory effects on the oxidative phosphorylation and on the electron transport chain, respectively. The inhibition of F1Fo-ATPase and succinate-dehydrogenase activities also corroborated the ability of mercury to inhibit ADP phosphorylation and the electron transport chain. This study brings new understanding on the mercury levels able to impair fish mitochondrial function, reinforcing the need for further assessing bioenergetics as a proxy for fish health status

  10. 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.

  11. Exposure to moderate concentrations of tropospheric ozone impairs tree stomatal response to carbon dioxide

    Energy Technology Data Exchange (ETDEWEB)

    Onandia, Gabriela [Department of Plant and Environmental Sciences, University of Gothenburg, P. O. Box 461, SE-405 30 Goeteborg (Sweden); Cavanilles Institute of Biodiversity and Evolutionary Biology, Department of Microbiology and Ecology, University of Valencia, E-46100 Burjassot, Valencia (Spain); Olsson, Anna-Karin; Barth, Sabine [Department of Plant and Environmental Sciences, University of Gothenburg, P. O. Box 461, SE-405 30 Goeteborg (Sweden); King, John S. [Department of Forestry and Environmental Resources, Campus Box 8002, North Carolina State University, Raleigh, NC 27695 (United States); Uddling, Johan, E-mail: johan.uddling@dpes.gu.se [Department of Plant and Environmental Sciences, University of Gothenburg, P. O. Box 461, SE-405 30 Goeteborg (Sweden)

    2011-10-15

    With rising concentrations of both atmospheric carbon dioxide (CO{sub 2}) and tropospheric ozone (O{sub 3}), it is important to better understand the interacting effects of these two trace gases on plant physiology affecting land-atmosphere gas exchange. We investigated the effect of growth under elevated CO{sub 2} and O{sub 3}, singly and in combination, on the primary short-term stomatal response to CO{sub 2} concentration in paper birch at the Aspen FACE experiment. Leaves from trees grown in elevated CO{sub 2} and/or O{sub 3} exhibited weaker short-term responses of stomatal conductance to both an increase and a decrease in CO{sub 2} concentration from current ambient level. The impairement of the stomatal CO{sub 2} response by O{sub 3} most likely developed progressively over the growing season as assessed by sap flux measurements. Our results suggest that expectations of plant water-savings and reduced stomatal air pollution uptake under rising atmospheric CO{sub 2} may not hold for northern hardwood forests under concurrently rising tropospheric O{sub 3}. - Exposure to moderate concentrations of tropospheric ozone impairs stomatal CO{sub 2} responsiveness of birch in the Aspen FACE experiment.

  12. 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.

  13. Rat lung macrophage tumor cytotoxin production: impairment by chronic in vivo cigarette smoke exposure.

    Science.gov (United States)

    Flick, D A; Gonzalez-Rothi, R J; Harris, J O; Gifford, G E

    1985-11-01

    Macrophages in the presence of bacteria-derived lipopolysaccharide (LPS) stimuli produce a soluble cytotoxin which is toxic to tumor cells. In this study, we examined various parameters of cytotoxin production from pulmonary lavage cells obtained from Fisher 344 cesarean-derived rats. Cultures of macrophages were derived from pulmonary lavage cells and stimulated in vitro with LPS. Cytotoxin production was assayed in vitro using an L-929 cell target assay. Pulmonary lavage preparations contained a relatively pure population of macrophages, and adherence studies revealed that nonadherent lavage cells contributed negligible amounts of cytotoxin, indicating that macrophages were responsible for cytotoxin production. After LPS stimulation, cytotoxin production became maximal within 10 h and thereafter plateaued. Doses of LPS above 0.1 microgram/ml were optimal for production, and in the absence of LPS, no cytotoxin was detected. Because cigarette smoke is the major etiological factor in the development of lung cancers and because smoking is known to profoundly alter the function of alveolar macrophages in humans and experimental animals, subsequent experiments examined the role of chronic cigarette smoke exposure on tumoricidal activity of lung macrophages. Rats were exposed in vivo for 8 wk to either cigarette smoke or air (sham-treated controls). When lavage cells were cultured and stimulated with LPS (1 microgram/ml), 5- to 10-fold less cytotoxin was produced by lavage cells from rats exposed to cigarette smoke. Similarly, using a direct cytotoxicity assay, lung macrophages of smoke-exposed animals also revealed marked impairment in cytotoxicity against L-929 cell targets, and this was noted over a wide range of macrophage:tumor target cell ratios. Another product of macrophages, interferon, was also decreased in rats exposed in vivo to cigarette smoke when compared to sham-treated controls. These results suggest that cigarette smoke exposure may impair pulmonary

  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. Neonatal lipopolysaccharide exposure induces long-lasting learning impairment, less anxiety-like response and hippocampal injury in adult rats

    OpenAIRE

    Wang, Kuo-Ching; Fan, Lir-Wan; Kaizaki, Asuka; Pang, Yi; Cai, Zhengwei; Tien, Lu-Tai

    2013-01-01

    Infection during early neonatal period has been shown to cause lasting neurological disabilities and is associated with the subsequent impairment in development of learning and memory ability and anxiety-related behavior in adults. We have previously reported that neonatal lipopolysaccharide (LPS) exposure resulted in cognitive deficits in juvenile rats (P21); thus, the goal of the present study was to determine whether neonatal LPS exposure has long-lasting effects in adult rats. After an LP...

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

    DEFF Research Database (Denmark)

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

    2013-01-01

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

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

    Science.gov (United States)

    Kemmler, Julia; Bindl, Ronny; McCook, Oscar; Wagner, Florian; Gröger, Michael; Wagner, Katja; Scheuerle, Angelika; Radermacher, Peter; Ignatius, Anita

    2015-01-01

    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. PMID:26147725

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

    Directory of Open Access Journals (Sweden)

    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.

  19. Nontypeable Haemophilus influenzae Clearance by Alveolar Macrophages Is Impaired by Exposure to Cigarette Smoke ▿ †

    Science.gov (United States)

    Martí-Lliteras, Pau; Regueiro, Verónica; Morey, Pau; Hood, Derek W.; Saus, Carles; Sauleda, Jaume; Agustí, Alvar G. N.; Bengoechea, José Antonio; Garmendia, Junkal

    2009-01-01

    Nontypeable Haemophilus influenzae (NTHI) is an opportunistic gram-negative pathogen that causes respiratory infections and is associated with progression of respiratory diseases. Cigarette smoke is a main risk factor for development of respiratory infections and chronic respiratory diseases. Glucocorticoids, which are anti-inflammatory drugs, are still the most common therapy for these diseases. Alveolar macrophages are professional phagocytes that reside in the lung and are responsible for clearing infections by the action of their phagolysosomal machinery and promotion of local inflammation. In this study, we dissected the interaction between NTHI and alveolar macrophages and the effect of cigarette smoke on this interaction. We showed that alveolar macrophages clear NTHI infections by adhesion, phagocytosis, and phagolysosomal processing of the pathogen. Bacterial uptake requires host actin polymerization, the integrity of plasma membrane lipid rafts, and activation of the phosphatidylinositol 3-kinase (PI3K) signaling cascade. Parallel to bacterial clearance, macrophages secrete tumor necrosis factor alpha (TNF-α) upon NTHI infection. In contrast, exposure to cigarette smoke extract (CSE) impaired alveolar macrophage phagocytosis, although NTHI-induced TNF-α secretion was not abrogated. Mechanistically, our data showed that CSE reduced PI3K signaling activation triggered by NTHI. Treatment of CSE-exposed cells with the glucocorticoid dexamethasone reduced the amount of TNF-α secreted upon NTHI infection but did not compensate for CSE-dependent phagocytic impairment. The deleterious effect of cigarette smoke was observed in macrophage cell lines and in human alveolar macrophages obtained from smokers and from patients with chronic obstructive pulmonary disease. PMID:19620348

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

    International Nuclear Information System (INIS)

    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

  1. 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.

  2. 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.

  3. In utero exposure to low dose arsenic via drinking water impairs early life lung mechanics in mice

    Science.gov (United States)

    2013-01-01

    Background Exposure to arsenic via drinking water is a significant environmental issue affecting millions of people around the world. Exposure to arsenic during foetal development has been shown to impair somatic growth and increase the risk of developing chronic respiratory diseases. The aim of this study was to determine if in utero exposure to low dose arsenic via drinking water is capable of altering lung growth and postnatal lung mechanics. Methods Pregnant C57BL/6 mice were given drinking water containing 0, 10 (current World Health Organisation (WHO) maximum contaminant level) or 100μg/L arsenic from gestational day 8 to birth. Birth outcomes and somatic growth were monitored. Plethysmography and the forced oscillation technique were used to collect measurements of lung volume, lung mechanics, pressure-volume curves and the volume dependence of lung mechanics in male and female offspring at two, four, six and eight weeks of age. Results In utero exposure to low dose arsenic via drinking water resulted in low birth weight and impaired parenchymal lung mechanics during infancy. Male offspring were more susceptible to the effects of arsenic on growth and lung mechanics than females. All alterations to lung mechanics following in utero arsenic exposure were recovered by adulthood. Conclusions Exposure to arsenic at the current WHO maximum contaminant level in utero impaired somatic growth and the development of the lungs resulting in alterations to lung mechanics during infancy. Deficits in growth and lung development in early life may contribute to the increased susceptibility of developing chronic respiratory disease in arsenic exposed human populations. PMID:23419080

  4. Rapid clearance of a structural isomer of bilirubin during phototherapy.

    OpenAIRE

    Ennever, J F; Costarino, A T; Polin, R A; Speck, W T

    1987-01-01

    During phototherapy for neonatal jaundice, bilirubin is converted into a variety of photoproducts. Determination of the relative importance of these photoproducts to the elimination of bilirubin requires knowledge of their rates of excretion. We have measured the rate at which the structural isomer of bilirubin, lumirubin, disappeared from the serum of nine jaundiced premature infants after the cessation of phototherapy. In all patients studied, the decline in serum lumirubin could be approxi...

  5. Bilirubin/Albumin Ratio for Predicting Acute Bilirubin-induced Neurologic Dysfunction

    Directory of Open Access Journals (Sweden)

    Gholamreza Esmaeeli Djavid

    2011-03-01

    Full Text Available Objective:The aim of this study was to evaluate the bilirubin albumin (B/A ratio in comparison with total serum bilirubin (TSB for predicting acute bilirubin-induced neurologic dysfunction (BIND. Methods:Fifty two term and near term neonates requiring phototherapy and exchange transfusion for severe hyperbilirubinemia in Childrens Medical Center, Tehran, Iran, during September 2007 to September 2008, were evaluated. Serum albumin and bilirubin were measured at admission. All neonates were evaluated for acute BIND based on clinical findings. Findings:Acute BIND developed in 5 (3.8% neonates. B/A ratio in patients with BIND was significantly higher than in patients without BIND (P<0.001. Receiver operation characteristics (ROC analysis identified a TSB cut off value of 25 mg/dL [area under the curve (AUC 0.945] with a sensitivity of 100% and specificity of 85%. Also, according to the ROC curve, B/A ratio cut off value for predicting acute BIND was 8 (bil mg/al g (AUC 0.957 with sensitivity of 100% and specificity of 94%. Conclusion:Based on our results, we suggest using B/A ratio in conjunction with TSB. This can improve the specificity and prevent unnecessary invasive therapy such as exchange transfusion in icteric neonates.

  6. Comparison of serum bilirubin estimation with transcutaneous bilirubinometry in neonates

    International Nuclear Information System (INIS)

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

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

    Directory of Open Access Journals (Sweden)

    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

  8. In vivo hydroquinone exposure alters circulating neutrophil activities and impairs LPS-induced lung inflammation in mice.

    Science.gov (United States)

    Ribeiro, André Luiz Teroso; Shimada, Ana Lúcia Borges; Hebeda, Cristina Bichels; de Oliveira, Tiago Franco; de Melo Loureiro, Ana Paula; Filho, Walter Dos Reis Pereira; Santos, Alcinéa Meigikos Dos Anjos; de Lima, Wothan Tavares; Farsky, Sandra Helena Poliselli

    2011-10-01

    Hydroquinone (HQ) is an environmental contaminant which causes immune toxicity. In this study, the effects of exposure to low doses of HQ on neutrophil mobilization into the LPS-inflamed lung were investigated. Male Swiss mice were exposed to aerosolized vehicle (control) or 12.5, 25 or 50ppm HQ (1h/day for 5 days). One hour later, oxidative burst, cell cycle, DNA fragmentation and adhesion molecules expressions in circulating neutrophils were determined by flow cytometry, and plasma malondialdehyde (MDA) levels were measured by HPLC. Also, 1h later the last exposures, inflammation was induced by LPS inhalation (0.1mg/ml/10min) and 3h later, the numbers of leukocytes in peripheral blood and in the bronchoalveolar lavage fluid (BALF) were determined using a Neubauer chamber and stained smears; adhesion molecules expressed on lung microvessel endothelial cells were quantified by immunohistochemistry; myeloperoxidase (MPO) activity was measured in the lung tissue by colorimetric assay; and cytokines in the BALF were determined by ELISA. In vivo HQ exposure augmented plasma MDA levels and oxidative activity of neutrophils, but did not cause alterations in cell cycle and DNA fragmentation. Under these conditions, the number of circulating leukocytes was not altered, but HQ exposure reduced LPS-induced neutrophil migration into the alveolar space, as these cells remained in the lung tissue. The impaired neutrophil migration into BALF may not be dependent on reduced cytokines secretions in the BALF and lung endothelial adhesion molecules expressions. However, HQ exposure increased the expression of β(2) and β(3) integrins and platelet-endothelial cell adhesion molecule-1 (PECAM-1) in neutrophils, which were not further enhanced by fMLP in vitro stimulation, indicating that HQ exposure activates circulating neutrophils, impairing further stimulatory responses. Therefore, it has been shown, for the first time, that neutrophils are target of lower levels of in vivo HQ

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

    Directory of Open Access Journals (Sweden)

    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.

  10. 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. PMID:25651083

  11. 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.

  12. Lead Exposure Impairs Hippocampus Related Learning and Memory by Altering Synaptic Plasticity and Morphology During Juvenile Period.

    Science.gov (United States)

    Wang, Tao; Guan, Rui-Li; Liu, Ming-Chao; Shen, Xue-Feng; Chen, Jing Yuan; Zhao, Ming-Gao; Luo, Wen-Jing

    2016-08-01

    Lead (Pb) is an environmental neurotoxic metal. Pb exposure may cause neurobehavioral changes, such as learning and memory impairment, and adolescence violence among children. Previous animal models have largely focused on the effects of Pb exposure during early development (from gestation to lactation period) on neurobehavior. In this study, we exposed Sprague-Dawley rats during the juvenile stage (from juvenile period to adult period). We investigated the synaptic function and structural changes and the relationship of these changes to neurobehavioral deficits in adult rats. Our results showed that juvenile Pb exposure caused fear-conditioned memory impairment and anxiety-like behavior, but locomotion and pain behavior were indistinguishable from the controls. Electrophysiological studies showed that long-term potentiation induction was affected in Pb-exposed rats, and this was probably due to excitatory synaptic transmission impairment in Pb-exposed rats. We found that NMDA and AMPA receptor-mediated current was inhibited, whereas the GABA synaptic transmission was normal in Pb-exposed rats. NR2A and phosphorylated GluR1 expression decreased. Moreover, morphological studies showed that density of dendritic spines declined by about 20 % in the Pb-treated group. The spine showed an immature form in Pb-exposed rats, as indicated by spine size measurements. However, the length and arborization of dendrites were unchanged. Our results suggested that juvenile Pb exposure in rats is associated with alterations in the glutamate receptor, which caused synaptic functional and morphological changes in hippocampal CA1 pyramidal neurons, thereby leading to behavioral changes. PMID:26141123

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

    Directory of Open Access Journals (Sweden)

    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.

  14. 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

  15. 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....

  16. 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

  17. 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

  18. Maternal nicotine exposure leads to impaired disulfide bond formation and augmented endoplasmic reticulum stress in the rat placenta.

    Directory of Open Access Journals (Sweden)

    Michael K Wong

    Full Text Available Maternal nicotine exposure has been associated with many adverse fetal and placental outcomes. Although underlying mechanisms remain elusive, recent studies have identified that augmented endoplasmic reticulum (ER stress is linked to placental insufficiency. Moreover, ER function depends on proper disulfide bond formation--a partially oxygen-dependent process mediated by protein disulfide isomerase (PDI and ER oxidoreductases. Given that nicotine compromised placental development in the rat, and placental insufficiency has been associated with poor disulfide bond formation and ER stress, we hypothesized that maternal nicotine exposure leads to both placental ER stress and impaired disulfide bond formation. To test this hypothesis, female Wistar rats received daily subcutaneous injections of either saline (vehicle or nicotine bitartrate (1 mg/kg for 14 days prior to mating and during pregnancy. Placentas were harvested on embryonic day 15 for analysis. Protein and mRNA expression of markers involved in ER stress (e.g., phosphorylated eIF2α, Grp78, Atf4, and CHOP, disulfide bond formation (e.g., PDI, QSOX1, VKORC1, hypoxia (Hif1α, and amino acid deprivation (GCN2 were quantified via Western blot and/or Real-time PCR. Maternal nicotine exposure led to increased expression of Grp78, phosphorylated eIF2α, Atf4, and CHOP (p<0.05 in the rat placenta, demonstrating the presence of augmented ER stress. Decreased expression of PDI and QSOX1 (p<0.05 reveal an impaired disulfide bond formation pathway, which may underlie nicotine-induced ER stress. Finally, elevated expression of Hif1α and GCN2 (p<0.05 indicate hypoxia and amino acid deprivation in nicotine-exposed placentas, respectively, which may also cause impaired disulfide bond formation and augmented ER stress. This study is the first to link maternal nicotine exposure with both placental ER stress and disulfide bond impairment in vivo, providing novel insight into the mechanisms underlying

  19. 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. PMID:26749233

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

    Directory of Open Access Journals (Sweden)

    Manoochehr Mahram

    2015-12-01

    Full Text Available 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.

  1. Transcutaneous Bilirubin Measurement in Preterm Neonates

    Directory of Open Access Journals (Sweden)

    Paymaneh Alizadeh Taheri

    2012-11-01

    Full Text Available Hyperbilirubinemia is a common problem during neonatal period especially in preterm neonates. Transcutaneous bilirubin measurement (TcB by special devices had been documented as an effective tool for predicting neonatal jaundice in full term neonate, but for preterm infants the present evidences are controversial. We carried out a prospective study in Shariati Hospital NICU. 126 paired TcB/total serum bilirubin (TSB measurements were obtained. TcB (on forehead and sternum were measured using JH2-1A device for every admitted preterm infant who clinically showed jaundice and TSB measurements was obtained within 30 min of TcB. 58 (46% were male and 68 (54% were female. The mean gestational age was 31 week and mean birth weight was 1728 ± 60 g. 30 percent of neonates were ill. The mean value obtained by TBS was 8.8 mg/dl and for frontal TcB was 8.2mg/dl and for sternal TcB was 7.4mg/dl. There were good correlation between TBS and TcB and the maximum correlation were seen in 33-37 weeks of gestation and birth weight more than 2500 g with forehead TcB measurement. Healthy preterm infants had significant correlation of TSB and TcB (r=0.56, P<0.001 and ill preterm neonate had r =0.82, P<0.001. The correlation between TBS and TcB with and without phototherapy was r=0.66, P=0.000 and r=0.69, P=0.000 respectively. Although TcB measurement may underestimate TBS but there is significant correlation between TcB and TBS in preterm cases even in ill neonate or who receiving phototherapy. This method can be used for determination of bilirbin level in preterm neonate and reduces the number of blood sampling.

  2. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  4. Combined exposure to endocrine disrupting pesticides impairs parturition, causes pup mortality and affects sexual differentiation in rats

    DEFF Research Database (Denmark)

    Jacobsen, Pernille Rosenskjold; Christiansen, Sofie; Boberg, Julie;

    2010-01-01

    Risk assessment is currently based on the no observed adverse effect levels (NOAELs) for single compounds. Humans are exposed to a mixture of chemicals and recent studies in our laboratory have shown that combined exposure to endocrine disrupters can cause adverse effects on male sexual development...... survival in our laboratory and the dose levels used ranged from 25 to 100% of this mixture. All dose levels caused increased gestation length and dose levels above 25% caused impaired parturition leading to markedly decreased number of live born offspring and high pup perinatal mortality. The sexual...

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

    Science.gov (United States)

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

    2014-01-01

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

  6. 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.

  7. External Validation of the Bilirubin–Atazanavir Nomogram for Assessment of Atazanavir Plasma Exposure in HIV-1-Infected Patients

    OpenAIRE

    Rekić, Dinko; Röshammar, Daniel; Bergstrand, Martin; Tarning, Joel; Calcagno, Andrea; D’Avolio, Antonio; Ormaasen, Vidar; Vigan, Marie; Barrail-Tran, Aurélie; Ashton, Michael; Gisslén, Magnus; Äbelö, Angela

    2012-01-01

    Atazanavir increases plasma bilirubin levels in a concentration-dependent manner. Due to less costly and readily available assays, bilirubin has been proposed as a marker of atazanavir exposure. In this work, a previously developed nomogram for detection of suboptimal atazanavir exposure is validated against external patient populations. The bilirubin nomogram was validated against 311 matching bilirubin and atazanavir samples from 166 HIV-1-infected Norwegian, French, and Italian patients on...

  8. Influence of bilirubin on surface tension properties of lung surfactant.

    OpenAIRE

    Amato, M; Schürch, S; Grunder, R; Bachofen, H.; Burri, P H

    1996-01-01

    AIM: To investigate the influence of bilirubin on the surface tension activity of a porcine derived (Curosurf) and synthetic (Exosurf) surfactant. METHODS: The captive bubble surfactometer at phospholipid doses of 0.5 mg/ml (low dose) and 1 mg/ml (high dose) in solutions of increasing bilirubin concentrations (0.25, 0.5, and 1.0 mg/ml) was used. RESULTS: Curosurf (without bilirubin) showed a higher surface f1p4ion activity than Exosurf, as shown by area compression of 30 (SD 0.6)% compared wi...

  9. 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...

  10. 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

    2016-01-01

    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. PMID:27578147

  11. 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.

  12. 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......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...

  13. 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

  14. Prenatal Nicotine Exposure Impairs the Proliferation of Neuronal Progenitors, Leading to Fewer Glutamatergic Neurons in the Medial Prefrontal Cortex.

    Science.gov (United States)

    Aoyama, Yuki; Toriumi, Kazuya; Mouri, Akihiro; Hattori, Tomoya; Ueda, Eriko; Shimato, Akane; Sakakibara, Nami; Soh, Yuka; Mamiya, Takayoshi; Nagai, Taku; Kim, Hyoung-Chun; Hiramatsu, Masayuki; Nabeshima, Toshitaka; Yamada, Kiyofumi

    2016-01-01

    Cigarette smoking during pregnancy is associated with various disabilities in the offspring such as attention deficit/hyperactivity disorder, learning disabilities, and persistent anxiety. We have reported that nicotine exposure in female mice during pregnancy, in particular from embryonic day 14 (E14) to postnatal day 0 (P0), induces long-lasting behavioral deficits in offspring. However, the mechanism by which prenatal nicotine exposure (PNE) affects neurodevelopment, resulting in behavioral deficits, has remained unclear. Here, we report that PNE disrupted the proliferation of neuronal progenitors, leading to a decrease in the progenitor pool in the ventricular and subventricular zones. In addition, using a cumulative 5-bromo-2'-deoxyuridine labeling assay, we evaluated the rate of cell cycle progression causing the impairment of neuronal progenitor proliferation, and uncovered anomalous cell cycle kinetics in mice with PNE. Accordingly, the density of glutamatergic neurons in the medial prefrontal cortex (medial PFC) was reduced, implying glutamatergic dysregulation. Mice with PNE exhibited behavioral impairments in attentional function and behavioral flexibility in adulthood, and the deficits were ameliorated by microinjection of D-cycloserine into the PFC. Collectively, our findings suggest that PNE affects the proliferation and maturation of progenitor cells to glutamatergic neuron during neurodevelopment in the medial PFC, which may be associated with cognitive deficits in the offspring. PMID:26105135

  15. Impaired anterior swim bladder inflation following exposure to the thyroid peroxidase inhibitor 2-mercaptobenzothiazole part II: Zebrafish.

    Science.gov (United States)

    Stinckens, Evelyn; Vergauwen, Lucia; Schroeder, Anthony L; Maho, Walid; Blackwell, Brett R; Witters, Hilda; Blust, Ronny; Ankley, Gerald T; Covaci, Adrian; Villeneuve, Daniel L; Knapen, Dries

    2016-04-01

    Disruption of the thyroid hormone (TH) system, an important mode of action, can lead to ecologically relevant adverse outcomes, especially during embryonic development. The present study characterizes the effects of disruption of TH synthesis on swim bladder inflation during zebrafish early-life stages using 2-mercaptobenzothiazole (MBT), a thyroid peroxidase (TPO) inhibitor. Zebrafish were exposed to different MBT concentrations until 120/168h post fertilization (hpf) and 32days post fertilization (dpf), in two sets of experiments, to investigate the effects of TPO inhibition on posterior and anterior swim bladder inflation respectively, as well as whole body thyroid hormone concentrations (triiodothyronine (T3) and its prohormone, thyroxine (T4)). At 120hpf, MBT did not directly impair posterior chamber inflation or size, while anterior chamber inflation and size was impaired at 32dpf. As previously shown in amphibians and mammals, we confirmed that MBT inhibits TPO in fish. Whole-body T4 decreased after MBT exposure at both time points, while T3 levels were unaltered. There was a significant relationship between T4 levels and the anterior chamber surface at 32dpf. The absence of effects on posterior chamber inflation can possibly be explained by maternal transfer of T4 into the eggs. These maternally derived THs are depleted at 32dpf and cannot offset TPO inhibition, resulting in impaired anterior chamber inflation. Therefore, we hypothesize that TPO inhibition only inhibits swim bladder inflation during late development, after depletion of maternally derived T4. In a previous study, we showed that iodothyronine deiodinase (ID) knockdown impaired posterior chamber inflation during early development. Our findings, in parallel with similar effects observed in fathead minnow (see part I, this issue) suggest that thyroid disruption impacts swim bladder inflation, and imply an important distinction among specific subtypes of TH disrupting chemicals. However, the

  16. 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.

  17. 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.

  18. Combined exposure to endocrine disrupting pesticides impairs parturition and causes pup mortality in rats

    DEFF Research Database (Denmark)

    Hansen, Pernille Reimer; Christiansen, Sofie; Boberg, Julie;

    Risk assessment is currently based on the no observed adverse effect level (NOAELs) for single compounds. Humans are exposed to a mixture of chemicals and epidemiological studies have reported some associations between endocrine disrupting effects and combined exposure to certain pesticides....... Although laboratory animal studies have shown that some endocrine disrupting pesticides can affect reproduction and sexual differentiation, individual pesticides may appear to be present in human tissues at too low levels to cause concern for adverse reproductive effects. However, recent studies in our...... laboratory have shown that combined exposure to endocrine disrupters can cause adverse effects on male sexual development, even though the doses of the single compounds are below their individual NOAELs for anti-androgenic effects. Here, we present results from range finding studies with combined exposure...

  19. Diethylhexyl phthalate exposure impairs follicular development and affects oocyte maturation in the mouse.

    Science.gov (United States)

    Zhang, Xi-Feng; Zhang, Lian-Jun; Li, Lan; Feng, Yan-Ni; Chen, Bo; Ma, Jin-Mei; Huynh, Evanna; Shi, Qing-Hua; De Felici, Massimo; Shen, Wei

    2013-06-01

    Diethylhexyl phthalate (DEHP) is an estrogen-like compound widely used as a commercial plasticizer and present in medical devices, tubing, food containers and packaging. It is considered an endocrine disruptor and studies on experimental animals showed that exposure to DEHP can alter the function of several organs including liver, kidneys, lungs and reproductive system, particularly the developing testes of prenatal and neonatal males. Exposure to DEHP has been proposed as a potential human health hazard. This study assessed the effects of DEHP on folliculogenesis and oocyte maturation using the mouse as the experimental model. Newborn female mice were hypodermically injected with DEHP at doses of 20 and 40 μg/kg per body weight following different exposure regimens during the weaning period. We found that DEHP altered both folliculogenesis and oocyte development. In particular, DEHP exposure significantly decreased the number of the primordial follicles at pubertal and adult age by possibly accelerating the rate of follicle recruitment dynamics, reduced and/or delayed the level of imprinted gene methylation in the oocytes and increased metaphase II spindle abnormalities in oocytes matured in vitro. Furthermore, the weight of pups and litter size of mothers exposed to DEHP were significantly lower than controls. Finally, the number of primordial follicles appeared significantly reduced also in the F1 offspring at the adult age. These results show that DEHP may have a number of adverse effects on oogenesis, especially when exposure occurs during early postnatal age, arising concerns about the exposure of human female infants and children to this compound.

  20. 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.

  1. 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.

  2. 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.

  3. Delay and impairment in brain development and function in rat offspring after maternal exposure to methylmercury

    NARCIS (Netherlands)

    Radonjic, M.; Cappaert, N.L.M.; Vries, E.F.J. de; Esch, C.E.F. de; Kuper, F.C.; Waarde, A. van; Dierckx, R.A.J.O.; Wadman, W.J.; Wolterbeek, A.P.M.; Stierum, R.H.; Groot, D.M.G. de

    2013-01-01

    Maternal exposure to the neurotoxin methylmercury (MeHg) has been shown to have adverse effects on neural development of the offspring in man. Little is known about the underlying mechanisms by which MeHg affects the developing brain. To explore the neurodevelopmental defects and the underlying mech

  4. Perinatal Exposure to Glufosinate Ammonium Herbicide Impairs Neurogenesis and Neuroblast Migration through Cytoskeleton Destabilization

    Science.gov (United States)

    Herzine, Ameziane; Laugeray, Anthony; Feat, Justyne; Menuet, Arnaud; Quesniaux, Valérie; Richard, Olivier; Pichon, Jacques; Montécot-Dubourg, Céline; Perche, Olivier; Mortaud, Stéphane

    2016-01-01

    Neurogenesis, a process of generating functional neurons from neural precursors, occurs throughout life in restricted brain regions such as the subventricular zone (SVZ). During this process, newly generated neurons migrate along the rostral migratory stream to the olfactory bulb to replace granule cells and periglomerular neurons. This neuronal migration is pivotal not only for neuronal plasticity but also for adapted olfactory based behaviors. Perturbation of this highly controlled system by exogenous chemicals has been associated with neurodevelopmental disorders. We reported recently that perinatal exposure to low dose herbicide glufosinate ammonium (GLA), leads to long lasting behavioral defects reminiscent of Autism Spectrum Disorder-like phenotype in the offspring (Laugeray et al., 2014). Herein, we demonstrate that perinatal exposure to low dose GLA induces alterations in neuroblast proliferation within the SVZ and abnormal migration from the SVZ to the olfactory bulbs. These disturbances are not only concomitant to changes in cell morphology, proliferation and apoptosis, but are also associated with transcriptomic changes. Therefore, we demonstrate for the first time that perinatal exposure to low dose GLA alters SVZ neurogenesis. Jointly with our previous work, the present results provide new evidence on the link between molecular and cellular consequences of early life exposure to the herbicide GLA and the onset of ASD-like phenotype later in life.

  5. 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. PMID:26019008

  6. 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. PMID:27472966

  7. Brief postnatal exposure to phenobarbital impairs passive-avoidance learning and sensorimotor gating in rats

    OpenAIRE

    Gutherz, Samuel B.; Kulick, Catherine V.; Soper, Colin; Kondratyev, Alexei; Gale, Karen; Forcelli, Patrick A.

    2014-01-01

    Phenobarbital is the most commonly utilized drug for the treatment of neonatal seizures. However, mounting preclinical evidence suggests that even brief exposure to phenobarbital in the neonatal period can induce neuronal apoptosis, alterations in synaptic development, and long-lasting changes in behavioral functions. In the present report, we treated neonatal rat pups with phenobarbital and evaluated behavior in adulthood. Pups were treated initially with a loading dose (80mg/kg) on postnata...

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

    Science.gov (United States)

    Huang, Chaobin; Li, Xiangdong

    2014-01-01

    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. PMID:24810582

  9. 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.

  10. 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.

  11. Respiratory impairment due to asbestos exposure in brake-lining workers

    International Nuclear Information System (INIS)

    There is extensive evidence that exposure to asbestos causes pulmonary parenchyma fibrosis, pleural disease, and malignant neoplasm in asbestos-exposed workers. However, few data concerning brake-lining workers are available in the literature. In this study, we aimed to assess the long-term effects of chrysotile asbestos exposure on lung function and the risk of asbestos-related diseases in brake-lining workers. Seventy-four asbestos-exposed workers who processed brake-lining products and 12 unexposed office workers were offered pulmonary function tests (spirometry and transfer actor) in 1992 and 1999. In 1999, the mean duration of asbestos exposure was 0.00±4.07 and 11.02±4.81 years (7-31 years) in non smoking and smoking asbestos workers, respectively. Transfer factor (TL, CO) and transfer coefficient (KCO) decline were significant in the 7-year follow-up in both smoking and non smoking asbestos workers. However, lung function indices of he control group, whom were all current smokers; were also found to be decreased, including FEF75, TL, CO and KCO. We found minimal reticular changes in 10 asbestos workers who were all current smokers, they underwent high-resolution computed tomography scans of the chest and we found that they ad peri bronchial thickening resulting from smoking. As a conclusion, even in the absence of radiographic asbestosis, TL, CO and KCO may decrease after mean 10-year duration of exposure to asbestos in brake-lining workers and this is more noticeable with cigarette burden

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

    Science.gov (United States)

    Li, Lan; Liu, Jing-Cai; Lai, Fang-Nong; Liu, Huan-Qi; Zhang, Xi-Feng; Dyce, Paul W; Shen, Wei; Chen, Hong

    2016-01-01

    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. PMID:26845775

  13. Emphysema and pulmonary impairment in coal miners: quantitative relationship with dust exposure and cigarette smoking

    Energy Technology Data Exchange (ETDEWEB)

    E.D. Kuempel; V. Vallyathan; F.H.Y. Green [National Institute for Occupational Safety and Health, Cincinnati, OH (United States)

    2009-07-01

    Coal miners have been shown to be at increased risk of developing chronic obstructive pulmonary diseases including emphysema. The objective of this study was to determine whether lifetime cumulative exposure to respirable coal mine dust is a significant predictor of developing emphysema at a clinically-relevant level of severity by the end of life, after controlling for cigarette smoking and other covariates. Clinically-relevant emphysema severity was determined from the association between individuals' lung function during life (forced expiratory volume in one second, FEV{sub 1}, as a percentage of predicted normal values) and emphysema severity at autopsy (as the proportion of lung tissue affected). In a logistic regression model, cumulative exposure to respirable coal mine dust was a statistically significant predictor of developing clinically-relevant emphysema severity, among both ever-smokers and never-smokers. The odds ratio for developing emphysema associated with FEV1 <80% at the cohort mean cumulative coal dust exposure (87 mg/m{sup 3} x yr) was 2.30 (1.46-3.64, 95% confidence limits), and at the cohort mean cigarette smoking (among smokers: 42 pack-years) was 1.95 (1.39-2.79). 20 refs., 2 figs., 2 tabs.

  14. Neurotoxic exposure and impairment of the chemical senses of taste and smell.

    Science.gov (United States)

    Doty, Richard L

    2015-01-01

    The chemical senses of taste and smell determine the flavor of foods and beverages, guide appropriate food intake, and warn of such environmental hazards as spoiled or poisonous food, leaking natural gas, smoke, and airborne pollutants. This chapter addresses the influences of neurotoxic exposures on human chemoreception and provides basic information on the adverse influences of such exposures on rodent epithelia. The focus of the chapter is in olfaction, given dearth of empiric research on the effects of neurotoxic chemical exposures on the sense of taste, i.e., sweet, sour, bitter, salty, and savory sensations. As will be apparent from the chapter, numerous neurotoxins--many of which are encountered in industrial workplaces--alter the ability to smell, including solvents, metals, and particulate matter. The olfactory system is particularly vulnerable to such agents since its receptors are more or less directly exposed to the outside environment. Importantly, some such agents can enter the brain via the olfactory nerve or surrounding perineural spaces, bypassing the blood-brain barrier and damaging central nervous system structures and inducing pathologic processes that appear to be similar to those seen in neurodegenerative diseases such as Alzheimer's and Parkinson's. PMID:26563795

  15. Emphysema and pulmonary impairment in coal miners: Quantitative relationship with dust exposure and cigarette smoking

    Science.gov (United States)

    Kuempel, E. D.; Vallyathan, V.; Green, F. H. Y.

    2009-02-01

    Coal miners have been shown to be at increased risk of developing chronic obstructive pulmonary diseases including emphysema. The objective of this study was to determine whether lifetime cumulative exposure to respirable coal mine dust is a significant predictor of developing emphysema at a clinically-relevant level of severity by the end of life, after controlling for cigarette smoking and other covariates. Clinically-relevant emphysema severity was determined from the association between individuals' lung function during life (forced expiratory volume in one second, FEV1, as a percentage of predicted normal values) and emphysema severity at autopsy (as the proportion of lung tissue affected). In a logistic regression model, cumulative exposure to respirable coal mine dust was a statistically significant predictor of developing clinically-relevant emphysema severity, among both ever-smokers and never-smokers. The odds ratio for developing emphysema associated with FEV1 <80% at the cohort mean cumulative coal dust exposure (87 mg/m3 x yr) was 2.30 (1.46-3.64, 95% confidence limits), and at the cohort mean cigarette smoking (among smokers: 42 pack-years) was 1.95 (1.39-2.79).

  16. Honey Bees' Behavior Is Impaired by Chronic Exposure to the Neonicotinoid Thiacloprid in the Field.

    Science.gov (United States)

    Tison, Léa; Hahn, Marie-Luise; Holtz, Sophie; Rößner, Alexander; Greggers, Uwe; Bischoff, Gabriela; Menzel, Randolf

    2016-07-01

    The decline of pollinators worldwide is of growing concern and has been related to the use of plant-protecting chemicals. Most studies have focused on three neonicotinoid insecticides (clothianidin, imidacloprid, and thiamethoxam) currently subject to a moratorium in the EU. Here, we focus on thiacloprid, a widely used cyano-substituted neonicotinoid thought to be less toxic to honey bees and of which use has increased in the last years. Honey bees (Apis mellifera carnica) were exposed chronically to thiacloprid in the field for several weeks at a sublethal concentration. Foraging behavior, homing success, navigation performance, and social communication were impaired, and thiacloprid residue levels increased both in the foragers and the nest mates over time. The effects observed in the field were not due to a repellent taste of the substance. For the first time, we present the necessary data for the risk evaluation of thiacloprid taken up chronically by honey bees in field conditions. PMID:27268938

  17. 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.

  18. Increased anxiety and impaired spatial memory in young adult rats following adolescent exposure to methylone.

    Science.gov (United States)

    Daniel, Jollee J; Hughes, Robert N

    2016-01-01

    This study investigated the possibility that treatment of adolescent rats with the substituted cathinone, 3,4-methylenedioxymethcathinone (methylone), might result in heightened anxiety and/or impaired memory during early adulthood, as has been shown for other designer drugs. For 10 consecutive days from 35days after birth (PND35-44, early adolescence) or 45days after birth (PND45-54, late adolescence), male and female PVG/c rats were administered saline or 8.0mg/kg methylone via intraperitoneal injection. When 90days old (early adulthood), their anxiety-related behavior was recorded in an open field and a light/dark box. Acoustic startle amplitude was also measured as well as their spatial memory which was determined by their ability to detect which arm of a Y maze had changed in brightness between an acquisition and a retention trial. Previously methylone-treated rats showed increased anxiety-related behavior only in the open field as reflected in decreased ambulation, and increased corner occupancy and defecation. In the latter two cases, the increases depended on the age of treatment. Also, for defecation, only male rats were affected. In addition, methylone-treated rats displayed signs of impaired spatial memory, independent of anxiety, through their reduced ability to detect a novel changed Y-maze arm. The results of the study suggested some possible consequences in adulthood of methylone use during adolescence. There were also several examples of female rats exhibiting higher overall frequencies of activity and anxiety-related responding than males that were consistent with them being the more active and less anxious of the two sexes. PMID:27178814

  19. Radiation-induced signaling results in mitochondrial impairment in mouse heart at 4 weeks after exposure to X-rays.

    Directory of Open Access Journals (Sweden)

    Zarko Barjaktarovic

    Full Text Available BACKGROUND: Radiation therapy treatment of breast cancer, Hodgkin's disease or childhood cancers expose the heart to high local radiation doses, causing an increased risk of cardiovascular disease in the survivors decades after the treatment. The mechanisms that underlie the radiation damage remain poorly understood so far. Previous data show that impairment of mitochondrial oxidative metabolism is directly linked to the development of cardiovascular disease. METHODOLOGY/PRINCIPAL FINDINGS: In this study, the radiation-induced in vivo effects on cardiac mitochondrial proteome and function were investigated. C57BL/6N mice were exposed to local irradiation of the heart with doses of 0.2 Gy or 2 Gy (X-ray, 200 kV at the age of eight weeks, the control mice were sham-irradiated. After four weeks the cardiac mitochondria were isolated and tested for proteomic and functional alterations. Two complementary proteomics approaches using both peptide and protein quantification strategies showed radiation-induced deregulation of 25 proteins in total. Three main biological categories were affected: the oxidative phophorylation, the pyruvate metabolism, and the cytoskeletal structure. The mitochondria exposed to high-dose irradiation showed functional impairment reflected as partial deactivation of Complex I (32% and Complex III (11%, decreased succinate-driven respiratory capacity (13%, increased level of reactive oxygen species and enhanced oxidation of mitochondrial proteins. The changes in the pyruvate metabolism and structural proteins were seen with both low and high radiation doses. CONCLUSION/SIGNIFICANCE: This is the first study showing the biological alterations in the murine heart mitochondria several weeks after the exposure to low- and high-dose of ionizing radiation. Our results show that doses, equivalent to a single dose in radiotherapy, cause long-lasting changes in mitochondrial oxidative metabolism and mitochondria-associated cytoskeleton

  20. 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...... 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...

  1. Emphysema and pulmonary impairment in coal miners: Quantitative relationship with dust exposure and cigarette smoking

    International Nuclear Information System (INIS)

    Coal miners have been shown to be at increased risk of developing chronic obstructive pulmonary diseases including emphysema. The objective of this study was to determine whether lifetime cumulative exposure to respirable coal mine dust is a significant predictor of developing emphysema at a clinically-relevant level of severity by the end of life, after controlling for cigarette smoking and other covariates. Clinically-relevant emphysema severity was determined from the association between individuals' lung function during life (forced expiratory volume in one second, FEV1, as a percentage of predicted normal values) and emphysema severity at autopsy (as the proportion of lung tissue affected). In a logistic regression model, cumulative exposure to respirable coal mine dust was a statistically significant predictor of developing clinically-relevant emphysema severity, among both ever-smokers and never-smokers. The odds ratio for developing emphysema associated with FEV1 3 x yr) was 2.30 (1.46-3.64, 95% confidence limits), and at the cohort mean cigarette smoking (among smokers: 42 pack-years) was 1.95 (1.39-2.79).

  2. 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.

  3. 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.

  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. 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

  6. 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. PMID:25209942

  7. 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.

  8. A Comparison between Transcutaneous Bilirubin (TcB and Total Serum Bilirubin (TSB Measurements in Term Neonates

    Directory of Open Access Journals (Sweden)

    Majid Mansouri

    2015-05-01

    Full Text Available Background: Transcutaneous bilirubinometry (TCB is a simple method for estimating bilirubin levels in neonates. This method is noninvasive, quick, and painless. We aimed to compare serum and cutaneous bilirubin measurements in term neonates.Method: In this descriptive cross-sectional study, 200 neonates with icter with birth weights of at least 2500 grams were studied. TCB was measured using a bilirubinometer three times on the forehead and mean levels were calculated. Then, during the subsequent 30 minutes blood samples were obtained and sent to the laboratory for determining the total serum bilirubin (TSB levels. Findings: Of the 200 neonates, 124 (62% were boys and 76 (38% were girls, with an age range of 1-22 days. The mean±SD serum and cutaneous bilirubin levels were 18.75±5.38 and 17.85±4.46 mg/dl, respectively. A high correlation (r=0.89 was observed between TSB and TCB. The sensitivity and specificity of cutaneous bilirubin measurement were 95.1% and 68%, respectively.Conclusions: Because of its high sensitivity, TCB can be a suitable tool for predicting neonatal icter. However, it is not a suitable substitute for TSB measurement in neonates at a high risk of jaundice.

  9. MiADMSA reverses impaired mitochondrial energy metabolism and neuronal apoptotic cell death after arsenic exposure in rats

    Energy Technology Data Exchange (ETDEWEB)

    Dwivedi, Nidhi; Mehta, Ashish; Yadav, Abhishek [Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Gwalior-474 002 (India); Binukumar, B.K.; Gill, Kiran Dip [Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh-160 012 (India); Flora, Swaran J.S., E-mail: sjsflora@hotmail.com [Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Gwalior-474 002 (India)

    2011-11-15

    Arsenicosis, due to contaminated drinking water, is a serious health hazard in terms of morbidity and mortality. Arsenic induced free radicals generated are known to cause cellular apoptosis through mitochondrial driven pathway. In the present study, we investigated the effect of arsenic interactions with various complexes of the electron transport chain and attempted to evaluate if there was any complex preference of arsenic that could trigger apoptosis. We also evaluated if chelation with monoisoamyl dimercaptosuccinic acid (MiADMSA) could reverse these detrimental effects. Our results indicate that arsenic exposure induced free radical generation in rat neuronal cells, which diminished mitochondrial potential and enzyme activities of all the complexes of the electron transport chain. Moreover, these complexes showed differential responses towards arsenic. These early events along with diminished ATP levels could be co-related with the later events of cytosolic migration of cytochrome c, altered bax/bcl{sub 2} ratio, and increased caspase 3 activity. Although MiADMSA could reverse most of these arsenic-induced altered variables to various extents, DNA damage remained unaffected. Our study for the first time demonstrates the differential effect of arsenic on the complexes leading to deficits in bioenergetics leading to apoptosis in rat brain. However, more in depth studies are warranted for better understanding of arsenic interactions with the mitochondria. -- Research highlights: Black-Right-Pointing-Pointer Arsenic impairs mitochondrial energy metabolism leading to neuronal apoptosis. Black-Right-Pointing-Pointer Arsenic differentially affects mitochondrial complexes, I - III and IV being more sensitive than complex II. Black-Right-Pointing-Pointer Arsenic-induced apoptosis initiates through ROS generation or impaired [Ca{sup 2+}]i homeostasis. Black-Right-Pointing-Pointer MiADMSA reverses arsenic toxicity via intracellular arsenic- chelation, antioxidant

  10. 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

    2016-07-01

    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. PMID:26446883

  11. Maternal Smoke Exposure Impairs the Long-Term Fertility of Female Offspring in a Murine Model.

    Science.gov (United States)

    Camlin, Nicole J; Sobinoff, Alexander P; Sutherland, Jessie M; Beckett, Emma L; Jarnicki, Andrew G; Vanders, Rebecca L; Hansbro, Philip M; McLaughlin, Eileen A; Holt, Janet E

    2016-02-01

    The theory of fetal origins of adult disease was first proposed in 1989, and in the decades since, a wide range of other diseases from obesity to asthma have been found to originate in early development. Because mammalian oocyte development begins in fetal life it has been suggested that environmental and lifestyle factors of the mother could directly impact the fertility of subsequent generations. Cigarette smoke is a known ovotoxicant in active smokers, yet disturbingly 13% of Australian and 12% of US women continue to smoke throughout pregnancy. The focus of our investigation was to characterize the adverse effects of smoking on ovary and oocyte quality in female offspring exposed in utero. Pregnant mice were nasally exposed to cigarette smoke for 12 wk throughout pregnancy/lactation, and ovary and oocyte quality of the F1 (maternal smoke exposed) generation was examined. Neonatal ovaries displayed abnormal somatic cell proliferation and increased apoptosis, leading to a reduction in follicle numbers. Further investigation found that altered somatic cell proliferation and reduced follicle number continued into adulthood; however, apoptosis did not. This reduction in follicles resulted in decreased oocyte numbers, with these oocytes found to have elevated levels of oxidative stress, altered metaphase II spindle, and reduced sperm-egg interaction. These ovarian and oocyte changes ultimately lead to subfertility, with maternal smoke-exposed animals having smaller litters and also taking longer to conceive. In conclusion, our results demonstrate that in utero and lactational exposure to cigarette smoke can have long-lasting effects on the fertility of the next generation of females. PMID:26764348

  12. 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.

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

    Science.gov (United States)

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

    2016-09-01

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

  14. Serum bilirubin kinetics in intermittent phototherapy of physiological jaundice.

    OpenAIRE

    Lau, S. P.; Fung, K P

    1984-01-01

    Thirty four term babies with physiological jaundice were subjected to continuous phototherapy and to two regimens of intermittent phototherapy. The difference in serum bilirubin kinetics between the three groups of treated babies was insignificant; a schedule of one in four hours of irradiation achieved the same treatment effect as continuous phototherapy.

  15. 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. PMID:27481656

  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. Solar Irradiation of Bilirubin: An Experiment in Photochemical Oxidation

    Science.gov (United States)

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

    2006-01-01

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

  18. 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

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

    International Nuclear Information System (INIS)

    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

  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. 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...

  2. 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

  3. 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

  4. 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.

  5. 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.

  6. 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.

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

    Science.gov (United States)

    Monette, M.Y.; Yada, T.; Matey, V.; McCormick, S.D.

    2010-01-01

    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??gl-1 Al), acid and low Al (LAl: pH 5.4, 11??gl-1 Al), acid and moderate Al (MAl: pH 5.3, 42??gl-1 Al), and acid and high Al (HAl: pH 5.4, 56??gl-1 Al) for two and six days. At each time-point, smolts were sampled directly from freshwater treatment tanks and after a 24h seawater challenge. Exposure to acid/MAl and acid/HAl led to accumulation of gill Al, substantial alterations in gill morphology, reduced gill Na+/K+-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- 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-course and severity of Al exposure. We propose that when smolts are

  8. Impairment of green-lipped mussel (Perna canaliculus) physiology by waterborne cadmium: Relationship to tissue bioaccumulation and effect of exposure duration

    Energy Technology Data Exchange (ETDEWEB)

    Chandurvelan, Rathishri, E-mail: rch118@uclive.ac.nz [School of Biological Sciences, University of Canterbury, Private Bag 4800, Christchurch 8140 (New Zealand); Marsden, Islay D., E-mail: islay.marsden@canterbury.ac.nz [School of Biological Sciences, University of Canterbury, Private Bag 4800, Christchurch 8140 (New Zealand); Gaw, Sally, E-mail: sally.gaw@canterbury.ac.nz [Department of Chemistry, University of Canterbury, Private Bag 4800, Christchurch 8140 (New Zealand); Glover, Chris N., E-mail: chris.glover@canterbury.ac.nz [School of Biological Sciences, University of Canterbury, Private Bag 4800, Christchurch 8140 (New Zealand)

    2012-11-15

    Laboratory studies were performed to assess the impact of acute and subchronic cadmium (Cd) exposure on the green-lipped mussel, Perna canaliculus. A 96 h median lethal concentration (LC{sub 50}) value of 8160 {mu}g L{sup -1} was determined, characterising this species as relatively tolerant to Cd exposure. Acute (96 h; at 2000 and 4000 {mu}g Cd L{sup -1}) and subchronic (28 d; at 200 and 2000 {mu}g Cd L{sup -1}) waterborne exposures were then conducted to investigate the impact of Cd exposure on physiological responses (e.g. clearance (feeding) rate, absorption efficiency, oxygen uptake, ammonia production, oxygen to nitrogen ratio, scope for growth) and tissue Cd accumulation. Cd accumulation in digestive gland showed saturation with respect to increasing exposure concentration, while the gill tissue Cd accumulation followed a positive linear relationship with Cd exposure level. Clearance rates declined during both acute and subchronic exposures at levels of 2000 {mu}g Cd L{sup -1} or higher. Impairments of clearance rates were strongly correlated with tissue Cd accumulation. Coupled with their importance as a food source, and their wide coastal distribution, these data suggests that P. canaliculus may be a species useful as an indicator species for trace metal pollution in coastal environments.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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. PMID:23195115

  14. 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

  15. Ambivalent property of bilirubin in human bile juice

    Directory of Open Access Journals (Sweden)

    Anna Blázovics, Péter Sípos, Ferenc Örsi,* Mervat Abdel Rahman

    2005-03-01

    Full Text Available Gallstones are formed as a result of many metabolic disorders e.g. chronic haemolytic anaemia, diabetes mellitus, ileal diseases, short bowel syndrome, gluten sensitive enteropathy, elevated serum lipids or Crohn's disease. The relationship between gallstone disease and free radical reactions is not known exactly even today. Free radicals are involved in many clinical conditions e.g. in hyperlipidemia and in fatty liver. Oxygen free radicals are produced and accumulated while the function of mitochondrial and microsomal electron transport or in peroxisomes and the activated arachidonic acid cascade. Spontaneous lipid peroxidation and oxygen free radical products of respiratory burst of Kupffer cells can be added to peroxide pool of liver tissue. Tissues, cells and subcellular particles exhibit different specific defence activities in pathological processes, which involve free radicals. The activity of microsomal P450 enzyme system and the microsomal structure are changed during pathological free radical attack and the cholesterol/bile acid ratio in bile juice is also altered. At the same time bilirubin metabolism can also be modified. Bile samples of 88 cholecystectomysed patients in both sexes (male: 29, female: 59 were examined. HPLC analysis (HP1090 liquid chromatograph with diode array detector was used for the detection of free bilirubin and bilirubin derivates. HP5890 gas chromatograph and flame ionization detector was used for fatty acid analysis. The induced chemiluminescence intensity was also determined in bile juice with (Berthold Lumat 9501 luminometer. As results show, the occurrence of C18:1 9, C18:2 6, C20:4 6 fatty acids were in high percentage in gallbladder bile in every case of randomly chosen 17 cholecystectomysed patients in both sexes suffered from cholecystitis chronica with gallstone. Lipid peroxidation products (diene conjugates and malondialdehyde were detected in all cases of bile as well. Mathematical statistical

  16. 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 ...

  17. Depurative capacity of molecular adsorbent recycling system (MARS): A focus on bilirubin removal.

    Science.gov (United States)

    Gong, D; Cruz, D; Ronco, C

    2008-10-01

    The molecular adsorbent recycling system (MARS) is now widely used in the treatment of patients with hepatic failure (HF). A great deal of interest has been directed toward its effect on clinical outcome, whereas its depurative capacity also needs attention. Bilirubin, a tightly albumin-bound toxin accumulating in patients with HF, is regarded as a surrogate to evaluate the depurative capacity of albumin-bound toxins by blood purification modalities. The removal of bilirubin by MARS is difficult to predict, because both the clearance of bilirubin and the reduction ratio of bilirubin after a single session differ between patients and sessions. A reduction of depurative capacity over the course of a treatment is observed. Furthermore, the later sessions are likely less efficient than previous ones. It cannot be taken for granted that the reduction of depurative capacity is due to the saturation and reduced efficiency of the adsorbent columns used in MARS. The answer lies in the property of bilirubin/albumin binding. The removal of bilirubin by MARS is a diffusion process, dependent on the free bilirubin concentration. Bilirubin binds to albumin in 3 ways with different affinity. High-affinity binding bilirubin is difficult to dissociate from albumin and is accompanied by a smaller free fraction, which means it is also difficult for MARS to remove. The factors affecting the free fraction of bilirubin will impact on bilirubin removal by MARS. Among them, the molar ratio of bilirubin to albumin is the most important one. Other factors include the interaction of other agents with bilirubin/albumin binding, the albumin concentration, plasma ion strength, and pH. PMID:19009505

  18. 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.

  19. 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.

  20. Hepatic microtubule acetylation and stability induced by chronic alcohol exposure impair nuclear translocation of STAT3 and STAT5B, but not Smad2/3.

    Science.gov (United States)

    Fernandez, David J; Tuma, Dean J; Tuma, Pamela L

    2012-12-15

    Although alcoholic liver disease is clinically well described, the molecular basis for alcohol-induced hepatotoxicity is not well understood. Previously, we found that alcohol exposure led to increased microtubule acetylation and stability in polarized, hepatic WIF-B cells and in livers from ethanol-fed rats. Because microtubules are known to regulate transcription factor nuclear translocation and dynamic microtubules are required for translocation of at least a subset of these factors, we examined whether alcohol-induced microtubule acetylation and stability impair nuclear translocation. We examined nuclear delivery of factors representing the two mechanisms by which microtubules regulate translocation. To represent factors that undergo directed delivery, we examined growth hormone-induced STAT5B translocation and IL-6-induced STAT3 translocation. To represent factors that are sequestered in the cytoplasm by microtubule attachment until ligand activation, we examined transforming growth factor-β-induced Smad2/3 translocation. We found that ethanol exposure selectively impaired translocation of the STATs, but not Smad2/3. STAT5B delivery was decreased to a similar extent by addition of taxol (a microtubule-stabilizing drug) or trichostatin A (a deacetylase inhibitor), agents that promote microtubule acetylation in the absence of alcohol. Thus the alcohol-induced impairment of STAT nuclear translocation can be explained by increased microtubule acetylation and stability. Only ethanol treatment impaired STAT5B activation, indicating that microtubules are not important for its activation by Jak2. Furthermore, nuclear exit was not changed in treated cells, indicating that this process is also independent of microtubule acetylation and stability. Together, these results raise the exciting possibility that deacetylase agonists may be effective therapeutics for the treatment of alcoholic liver disease. PMID:23064763

  1. 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.

  2. Neurobehavioral impairments, generation of oxidative stress and release of pro-apoptotic factors after chronic exposure to sulphur mustard in mouse brain

    International Nuclear Information System (INIS)

    Recent global events have focused attention on the potential threat of international and domestic chemical terrorism, as well as the possibility of chemical warfare proliferation. Sulphur mustard (SM) is one of the potent chemical warfare agents (CWA), which initiates a cascade of events that converge on the redox mechanisms common to brain injury. The present study was designed to examine the effects of chronic SM exposure on neurobehavioral impairments, mitochondrial oxidative stress in male Swiss Albino mice and its role in inducing apoptotic neuronal cell death. The animals were divided into four groups (control, low, medium and high dose) of 5 animals each. Exposure to SM was given percutaneously daily for 12 weeks. The results demonstrated impairment in neurobehavioral indices viz. rota rod, passive avoidance and water maze tests in a dose dependent manner. There was a significant increase in lipid peroxidation and protein carbonyl content whereas, decrease in the activity of manganese superoxide dismutase (MnSOD), glutathione reductase and glutathione peroxidase suggesting impaired antioxidant defense system. Immunoblotting of cytochrome c, Bcl-2, Bax and activation of caspase-3 suggest induction of apoptosis in a dose dependent manner. Finally, increased p53 expression suggests that it may target the mitochondrial pathway for inducing apoptosis in response to DNA damage signals. In conclusion, chronic SM exposure may have the potential to generate oxidative stress which may trigger the release of cytochrome c as well as caspase-3 activation in neurons leading to cell death by apoptosis in a dose dependent manner which may in the end be responsible for the disruption of cognitive functions in mice.

  3. "The effect of fluid supplementation on serum bilirubin level during phototerapy in term infants "

    OpenAIRE

    Torkaman M; Afsharpeyman SH; Khalili Matinzadeh Z; Amirsalary S; Kavehmanesh Z; Hashemi S.A.

    2007-01-01

    Background: Jaundice is a common and benign problem in neonatal period. Several therapeutic procedures for decreasing of serum bilirubin level has been recommended. phototherapy is most common them. Our goal Form this study is the evaluation of serum therapy effects in decreasing of serum bilirubin concentration in icteric infants that are treated with phototherapy. Methods: This is a prospective clinical trial in Najmeih Hospital in 2002. In this study 80 term icteric infants with bilirubin ...

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

    OpenAIRE

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

    2015-01-01

    Objective: To investigate bilirubin-induced lung alveolar epithelial cell injury together with the protection afforded by dexmedetomidine. Design: Prospective, randomized, controlled study. Setting: Research laboratory. Subjects: Sprague Dawley rats. Interventions: Alveolar epithelial A549 cell lines were cultured and received bilirubin (from 0 to 160 μM) to explore the protective pathway of dexmedetomidine on bilirubin-induced alveolar epithelial cell injury assessed by immunochemistry and f...

  5. In vitro displacement of bilirubin by antibiotics and 2-hydroxybenzoylglycine in newborns.

    OpenAIRE

    Wadsworth, S J; Suh, B

    1988-01-01

    Hyperbilirubinemia is frequently observed in neonates, and serious neurological complications such as kernicterus can be precipitated when the concentration of unconjugated bilirubin is abnormally increased. The administration of drugs which bind to albumin and compete with bilirubin can increase the possibility of such a complication. To test the bilirubin-displacing activity of pharmacological agents that are used with newborns, 52 antimicrobial agents were investigated in vitro. A glycine ...

  6. An hour-specific transcutaneous bilirubin nomogram for Mongolian neonates

    OpenAIRE

    Akahira-Azuma, Moe; Yonemoto, Naohiro; Mori, Rintaro; Hosokawa, Shinichi; Matsushita, Takeji; Sukhbat, Khulan; Nansal, Gerelmaa; Bavuusuren, Bayasgalantai; Shonkhuuz, Enkhtur

    2015-01-01

    Transcutaneous bilirubin (TcB) nomograms have been developed for different populations. However, the TcB level, rate of rise and peak varies among countries and ethnicities. The aim of this study was to establish an hour-specific TcB nomogram for healthy term and late preterm Mongolian neonates during the first 144 h after birth. A total of 5084 TcB measurements from 1297 healthy neonates (gestational age ≥35 weeks, birth weight ≥2000 g) were obtained from October 2012 to October 2013. All me...

  7. Novel 14S,21-dihydroxy-docosahexaenoic acid Rescues Wound Healing and Associated Angiogenesis Impaired by Acute Ethanol Intoxication/Exposure

    OpenAIRE

    Tian, Haibin; Lu, Yan; Shah, Shraddha P.; Hong, Song

    2010-01-01

    Acute ethanol intoxication and exposure (AE) has been known to impair wound healing and associated angiogenesis. Here we found that AE diminished the formation of novel reparative lipid mediator 14S,21-dihydroxy-docosa-4Z,7Z,10Z,12E,16Z,19Z-hexaenoic acid (14S,21-diHDHA) and its biosynthetic intermediate 14S-hydroxy-DHA (14S-HDHA) from docosahexaenoic acid (DHA) in murine wounds. However, AE did not reduce the formation of DHA and the intermediate 21-HDHA. These results indicate that in the b...

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

    DEFF Research Database (Denmark)

    Honoré, B

    1987-01-01

    A stopped-flow technique was used to study the spectral changes occurring in bilirubin-albumin following a pH jump as well as following binding of bilirubin at 25 degrees C. The changes were studied in two wavelength ranges, 280-310 nm (tyrosine residues) and 400-510 nm (bound bilirubin......). The 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...

  9. 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)...

  10. 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....

  11. Long-Term Air Pollution and Traffic Noise Exposures and Mild Cognitive Impairment in Older Adults: A Cross-Sectional Analysis of the Heinz Nixdorf Recall Study

    Science.gov (United States)

    Tzivian, Lilian; Dlugaj, Martha; Winkler, Angela; Weinmayr, Gudrun; Hennig, Frauke; Fuks, Kateryna B.; Vossoughi, Mohammad; Schikowski, Tamara; Weimar, Christian; Erbel, Raimund; Jöckel, Karl-Heinz; Moebus, Susanne; Hoffmann, Barbara

    2016-01-01

    Background: Mild cognitive impairment (MCI) describes the intermediate state between normal cognitive aging and dementia. Adverse effects of air pollution (AP) on cognitive functions have been proposed, but investigations of simultaneous exposure to noise are scarce. Objectives: We analyzed the cross-sectional associations of long-term exposure to AP and traffic noise with overall MCI and amnestic (aMCI) and nonamnestic (naMCI) MCI. Methods: At the second examination of the population-based Heinz Nixdorf Recall study, cognitive assessment was completed in 4,086 participants who were 50–80 years old. Of these, 592 participants were diagnosed as having MCI (aMCI, n = 309; naMCI, n = 283) according to previously published criteria using five neuropsychological subtests. We assessed long-term residential concentrations for size-fractioned particulate matter (PM) and nitrogen oxides with land use regression, and for traffic noise [weighted 24-hr (LDEN) and night-time (LNIGHT) means]. Logistic regression models adjusted for individual risk factors were calculated to estimate the association of environmental exposures with MCI in single- and two-exposure models. Results: Most air pollutants and traffic noise were associated with overall MCI and aMCI. For example, an interquartile range increase in PM2.5 and a 10 A-weighted decibel [dB(A)] increase in LDEN were associated with overall MCI as follows [odds ratio (95% confidence interval)]: 1.16 (1.05, 1.27) and 1.40 (1.03, 1.91), respectively, and with aMCI as follows: 1.22 (1.08, 1.38) and 1.53 (1.05, 2.24), respectively. In two-exposure models, AP and noise associations were attenuated [e.g., for aMCI, PM2.5 1.13 (0.98, 1.30) and LDEN 1.46 (1.11, 1.92)]. Conclusions: Long-term exposures to air pollution and traffic noise were positively associated with MCI, mainly with the amnestic subtype. Citation: Tzivian L, Dlugaj M, Winkler A, Weinmayr G, Hennig F, Fuks KB, Vossoughi M, Schikowski T, Weimar C, Erbel R, Jöckel KH

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

    International Nuclear Information System (INIS)

    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 μM) 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

  13. 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.

  14. 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 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.

  15. 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.

  16. 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

  17. Therapeutic and space radiation exposure of mouse brain causes impaired DNA repair response and premature senescence by chronic oxidant production

    OpenAIRE

    Suman, Shubhankar; Rodriguez, Olga C.; Winters, Thomas A.; Fornace, Albert J.; Albanese, Chris; Datta, Kamal

    2013-01-01

    Despite recent epidemiological evidences linking radiation exposure and a number of human ailments including cancer, mechanistic understanding of how radiation inflicts long-term changes in cerebral cortex, which regulates important neuronal functions, remains obscure. The current study dissects molecular events relevant to pathology in cerebral cortex of 6 to 8 weeks old female C57BL/6J mice two and twelve months after exposure to a γ radiation dose (2 Gy) commonly employed in fractionated r...

  18. Short exposure to a diet rich in both fat and sugar or sugar alone impairs place, but not object recognition memory in rats.

    Science.gov (United States)

    Beilharz, Jessica E; Maniam, Jayanthi; Morris, Margaret J

    2014-03-01

    High energy diets have been shown to impair cognition however, the rapidity of these effects, and the dietary component/s responsible are currently unclear. We conducted two experiments in rats to examine the effects of short-term exposure to a diet rich in sugar and fat or rich in sugar on object (perirhinal-dependent) and place (hippocampal-dependent) recognition memory, and the role of inflammatory mediators in these responses. In Experiment 1, rats fed a cafeteria style diet containing chow supplemented with lard, cakes, biscuits, and a 10% sucrose solution performed worse on the place, but not the object recognition task, than chow fed control rats when tested after 5, 11, and 20 days. In Experiment 2, rats fed the cafeteria style diet either with or without sucrose and rats fed chow supplemented with sucrose also performed worse on the place, but not the object recognition task when tested after 5, 11, and 20 days. Rats fed the cafeteria diets consumed five times more energy than control rats and exhibited increased plasma leptin, insulin and triglyceride concentrations; these were not affected in the sucrose only rats. Rats exposed to sucrose exhibited both increased hippocampal inflammation (TNF-α and IL-1β mRNA) and oxidative stress, as indicated by an upregulation of NRF1 mRNA compared to control rats. In contrast, these markers were not significantly elevated in rats that received the cafeteria diet without added sucrose. Hippocampal BDNF and neuritin mRNA were similar across all groups. These results show that relatively short exposures to diets rich in both fat and sugar or rich in sugar, impair hippocampal-dependent place recognition memory prior to the emergence of weight differences, and suggest a role for oxidative stress and neuroinflammation in this impairment.

  19. Short exposure to a diet rich in both fat and sugar or sugar alone impairs place, but not object recognition memory in rats.

    Science.gov (United States)

    Beilharz, Jessica E; Maniam, Jayanthi; Morris, Margaret J

    2014-03-01

    High energy diets have been shown to impair cognition however, the rapidity of these effects, and the dietary component/s responsible are currently unclear. We conducted two experiments in rats to examine the effects of short-term exposure to a diet rich in sugar and fat or rich in sugar on object (perirhinal-dependent) and place (hippocampal-dependent) recognition memory, and the role of inflammatory mediators in these responses. In Experiment 1, rats fed a cafeteria style diet containing chow supplemented with lard, cakes, biscuits, and a 10% sucrose solution performed worse on the place, but not the object recognition task, than chow fed control rats when tested after 5, 11, and 20 days. In Experiment 2, rats fed the cafeteria style diet either with or without sucrose and rats fed chow supplemented with sucrose also performed worse on the place, but not the object recognition task when tested after 5, 11, and 20 days. Rats fed the cafeteria diets consumed five times more energy than control rats and exhibited increased plasma leptin, insulin and triglyceride concentrations; these were not affected in the sucrose only rats. Rats exposed to sucrose exhibited both increased hippocampal inflammation (TNF-α and IL-1β mRNA) and oxidative stress, as indicated by an upregulation of NRF1 mRNA compared to control rats. In contrast, these markers were not significantly elevated in rats that received the cafeteria diet without added sucrose. Hippocampal BDNF and neuritin mRNA were similar across all groups. These results show that relatively short exposures to diets rich in both fat and sugar or rich in sugar, impair hippocampal-dependent place recognition memory prior to the emergence of weight differences, and suggest a role for oxidative stress and neuroinflammation in this impairment. PMID:24309633

  20. Radiation-Induced Signaling Results in Mitochondrial Impairment in Mouse Heart at 4 Weeks after Exposure to X-Rays

    OpenAIRE

    Zarko Barjaktarovic; Dominik Schmaltz; Alena Shyla; Omid Azimzadeh; Sabine Schulz; Julia Haagen; Wolfgang Dörr; Hakan Sarioglu; Alexander Schäfer; Atkinson, Michael J.; Hans Zischka; Soile Tapio

    2011-01-01

    BACKGROUND: Radiation therapy treatment of breast cancer, Hodgkin's disease or childhood cancers expose the heart to high local radiation doses, causing an increased risk of cardiovascular disease in the survivors decades after the treatment. The mechanisms that underlie the radiation damage remain poorly understood so far. Previous data show that impairment of mitochondrial oxidative metabolism is directly linked to the development of cardiovascular disease. METHODOLOGY/PRINCIPAL FINDINGS: I...

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

    Science.gov (United States)

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

    2016-04-21

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

  2. 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.

  3. 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

  4. 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).

  5. 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.

  6. 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

  7. 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...... method, based upon a difference of light absorption spectrum for free and bound bilirubin. The observations were supplemented with previous data from an independent technique, measurement of oxidation rates of free bilirubin with hydrogen peroxide and peroxidase. A continuous isotherm was obtained......, showing binding of at least 4 mol bilirubin per mole albumin with the following stoichiometric binding constants, 1.11 X 10(8), 1.7 X 10(7), 8 X 10(5), and 4 X 10(4) M-1 at pH 8.2, ionic strength 0.15 M, 25 degrees C. The binding is anticooperative at all steps. A saturation level was not reached...

  8. 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...

  9. Paternal BPA exposure in early life alters Igf2 epigenetic status in sperm and induces pancreatic impairment in rat offspring.

    Science.gov (United States)

    Mao, Zhenxing; Xia, Wei; Chang, Huailong; Huo, Wenqian; Li, Yuanyuan; Xu, Shunqing

    2015-11-01

    Exposure to endocrine disruptors in utero appears to alter epigenetics in the male germ-line and subsequently promote adult-onset disease in subsequent generations. Fetal exposure to bisphenol A (BPA), a highly prevalent endocrine disruptor in environment, has been shown to alter epigenetic modification and result in glucose intolerance in adulthood. However, whether fetal exposure to BPA can induce epigenetic modification and phenotypic changes in their subsequent offspring are still unclear. The present study was designed to investigate whether exposure to BPA in early life induced glucose intolerance in the offspring through male germ line, and the underlying epigenetic molecular basis. F0 pregnant SD rats were received corn oil or 40 μg/kg/day of BPA during gestation and lactation. F1 male rats were maintained to generate F2 offspring by mating with untreated female rats. Both the F1 rats after weaning and the F2 offspring were not received any other treatments. Our results showed that male F2 offspring in the BPA group exhibited glucose intolerance and β-cell dysfunction. Decreased expression of Igf2 and associated hypermethylation of Igf2 were observed in islets of male F2 offspring. In addition, similar effects were observed in female F2 animals, but the effects were more pronounced in males. Moreover, abnormal expression and methylation of Igf2 was observed in sperm of adult F1 male rats, indicating that epigenetic modification in germ cells can be partly progressed to the next generation. Overall, our study suggests that BPA exposure during early life can result in generational transmission of glucose intolerance and β-cell dysfunction in the offspring through male germ line, which is associated with hypermethylation of Igf2 in islets. The changes of epigenetics in germ cells may contribute to this generational transmission. PMID:26276081

  10. 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...

  11. Repeated exposures to low-level chlorpyrifos results in impairments in sustained attention and increased impulsivity in rats

    OpenAIRE

    Middlemore-Risher, M.L.; Buccafusco, J.J.; Terry, A.V.

    2010-01-01

    Organophosphates such as chlorpyrifos (CPF) are among the most commonly used pesticides in the world. Therefore, it is not surprising that measurable levels of organophosphates (including CPF) are found in over 50% of fresh fruits, vegetables and grains that we consume and that approximately 80% of adults in the US have detectable levels of CPF metabolites in their urine. It is well known that acute exposure to organophosphates can cause cognitive deficits; however, the effects of daily or in...

  12. Therapeutic and space radiation exposure of mouse brain causes impaired DNA repair response and premature senescence by chronic oxidant production.

    Science.gov (United States)

    Suman, Shubhankar; Rodriguez, Olga C; Winters, Thomas A; Fornace, Albert J; Albanese, Chris; Datta, Kamal

    2013-08-01

    Despite recent epidemiological evidences linking radiation exposure and a number of human ailments including cancer, mechanistic understanding of how radiation inflicts long-term changes in cerebral cortex, which regulates important neuronal functions, remains obscure. The current study dissects molecular events relevant to pathology in cerebral cortex of 6 to 8 weeks old female C57BL/6J mice two and twelve months after exposure to a γ radiation dose (2 Gy) commonly employed in fractionated radiotherapy. For a comparative study, effects of 1.6 Gy heavy ion 56Fe radiation on cerebral cortex were also investigated, which has implications for space exploration. Radiation exposure was associated with increased chronic oxidative stress, oxidative DNA damage, lipid peroxidation, and apoptosis. These results when considered with decreased cortical thickness, activation of cell-cycle arrest pathway, and inhibition of DNA double strand break repair factors led us to conclude to our knowledge for the first time that radiation caused aging-like pathology in cerebral cortical cells and changes after heavy ion radiation were more pronounced than γ radiation. PMID:23928451

  13. Maternal DHA supplementation protects rat offspring against impairment of learning and memory following prenatal exposure to valproic acid.

    Science.gov (United States)

    Gao, Jingquan; Wu, Hongmei; Cao, Yonggang; Liang, Shuang; Sun, Caihong; Wang, Peng; Wang, Ji; Sun, Hongli; Wu, Lijie

    2016-09-01

    Docosahexaenoic acid (22:6n-3; DHA) is known to play a critical role in postnatal brain development. However, there have been no studies investigating the preventive effect of DHA on prenatal valproic acid (VPA)-induced behavioral and molecular alterations in offspring. The present study was to evaluate the neuroprotective effects in offspring using maternal feeding of DHA to rats exposed to VPA in pregnancy. In the present study, rats were exposed to VPA on day 12.5 of pregnancy; DHA was administered at the dosages of 100, 300 and 500 mg/kg/day for 3 weeks from day 1 to 21 of pregnancy. The results showed that maternal feeding of DHA to the prenatal exposed to VPA (1) prevented VPA-induced learning and memory impairment but did not change social-related behavior, (2) increased total DHA content in offspring plasma and hippocampus, (3) rescued VPA-induced neuronal loss and apoptosis of pyramidal cells in hippocampal CA1, (4) influenced the content of malondialdehyde and glutathione and the activities of superoxide dismutase and glutathione in the hippocampus, (5) altered levels of apoptosis-related proteins (Bcl-2, Bax and caspase-3) and inhibited the activity of caspase-3 in offspring hippocampus and (6) enhanced relative levels of p-CaMKII and p-CREB proteins in the hippocampus. These findings suggest that maternal feeding with DHA may prevent prenatal VPA-induced impairment of learning and memory, normalize several different molecules associated with oxidative stress and apoptosis in the hippocampus of offspring, and exert preventive effects on prenatal VPA-induced brain dysfunction. PMID:27469996

  14. 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.

  15. 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.

  16. [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.

  17. 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.

  18. 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. PMID:26466515

  19. 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.

  20. 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...

  1. 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.

    Science.gov (United States)

    Romero-Martínez, Ángel; Lila, Marisol; Catalá-Miñana, Alba; Williams, Ryan K; Moya-Albiol, Luis

    2013-08-01

    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. PMID:23965927

  2. Broad-spectrum antibiotic or G-CSF as potential countermeasures for impaired control of bacterial infection associated with an SPE exposure during spaceflight.

    Directory of Open Access Journals (Sweden)

    Minghong Li

    Full Text Available A major risk for astronauts during prolonged space flight is infection as a result of the combined effects of microgravity, situational and confinement stress, alterations in food intake, altered circadian rhythm, and radiation that can significantly impair the immune system and the body's defense systems. We previously reported a massive increase in morbidity with a decrease in the ability to control a bacterial challenge when mice were maintained under hindlimb suspension (HS conditions and exposed to solar particle event (SPE-like radiation. HS and SPE-like radiation treatment alone resulted in a borderline significant increase in morbidity. Therefore, development and testing of countermeasures that can be used during extended space missions in the setting of exposure to SPE radiation becomes a serious need. In the present study, we investigated the efficacy of enrofloxacin (an orally bioavailable antibiotic and Granulocyte colony stimulating factor (G-CSF (Neulasta on enhancing resistance to Pseudomonas aeruginosa infection in mice subjected to HS and SPE-like radiation. The results revealed that treatment with enrofloxacin or G-CSF enhanced bacterial clearance and significantly decreased morbidity and mortality in challenged mice exposed to suspension and radiation. These results establish that antibiotics, such as enrofloxacin, and G-CSF could be effective countermeasures to decrease the risk of bacterial infections after exposure to SPE radiation during extended space flight, thereby reducing both the risk to the crew and the danger of mission failure.

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. Single exposure to cocaine impairs aspartate uptake in the pre-frontal cortex via dopamine D1-receptor dependent mechanisms.

    Science.gov (United States)

    Sathler, Matheus Figueiredo; Stutz, Bernardo; Martins, Robertta Silva; Dos Santos Pereira, Maurício; Pecinalli, Ney Roner; Santos, Luis E; Taveira-da-Silva, Rosilane; Lowe, Jennifer; de Freitas, Isis Grigorio; de Melo Reis, Ricardo Augusto; Manhães, Alex C; Kubrusly, Regina C C

    2016-08-01

    Dopamine and glutamate play critical roles in the reinforcing effects of cocaine. We demonstrated that a single intraperitoneal administration of cocaine induces a significant decrease in [(3)H]-d-aspartate uptake in the pre-frontal cortex (PFC). This decrease is associated with elevated dopamine levels, and requires dopamine D1-receptor signaling (D1R) and adenylyl cyclase activation. The effect was observed within 10min of cocaine administration and lasted for up to 30min. This rapid response is related to D1R-mediated cAMP-mediated activation of PKA and phosphorylation of the excitatory amino acid transporters EAAT1, EAAT2 and EAAT3. We also demonstrated that cocaine exposure increases extracellular d-aspartate, l-glutamate and d-serine in the PFC. Our data suggest that cocaine activates dopamine D1 receptor signaling and PKA pathway to regulate EAATs function and extracellular EAA level in the PFC. PMID:27208619

  8. 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.

  9. Fluoride and arsenic exposure impairs learning and memory and decreases mGluR5 expression in the hippocampus and cortex in rats.

    Directory of Open Access Journals (Sweden)

    Shoufang Jiang

    Full Text Available Fluoride and arsenic are two common inorganic contaminants in drinking water that are associated with impairment in child development and retarded intelligence. The present study was conducted to explore the effects on spatial learning, memory, glutamate levels, and group I metabotropic glutamate receptors (mGluRs expression in the hippocampus and cortex after subchronic exposure to fluoride, arsenic, and a fluoride and arsenic combination in rats. Weaned male Sprague-Dawley rats were assigned to four groups. The control rats drank tap water. Rats in the three exposure groups drank water with sodium fluoride (120 mg/L, sodium arsenite (70 mg/L, and a sodium fluoride (120 mg/L and sodium arsenite (70 mg/L combination for 3 months. Spatial learning and memory was measured in Morris water maze. mGluR1 and mGluR5 mRNA and protein expression in the hippocampus and cortex was detected using RT-PCR and Western blot, respectively. Compared with controls, learning and memory ability declined in rats that were exposed to fluoride and arsenic both alone and combined. Combined fluoride and arsenic exposure did not have a more pronounced effect on spatial learning and memory compared with arsenic and fluoride exposure alone. Compared with controls, glutamate levels decreased in the hippocampus and cortex of rats exposed to fluoride and combined fluoride and arsenic, and in cortex of arsenic-exposed rats. mGluR5 mRNA and protein expressions in the hippocampus and mGluR5 protein expression in the cortex decreased in rats exposed to arsenic alone. Interestingly, compared with fluoride and arsenic exposure alone, fluoride and arsenic combination decreased mGluR5 mRNA expression in the cortex and protein expression in the hippocampus, suggesting a synergistic effect of fluoride and arsenic. These data indicate that fluoride and arsenic, either alone or combined, can decrease learning and memory ability in rats. The mechanism may be associated with changes of

  10. 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.

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

    International Nuclear Information System (INIS)

    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. 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

  13. 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.

  14. 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.

  15. 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.

  16. 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.

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

    OpenAIRE

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

    2007-01-01

    Management of newborn bilirubin spans the inpatient and outpatient continuum of care. Intermountain Healthcare has developed and implemented a web-based tool for managing bilirubin that follows newborn patients across care settings and providers with a consistent plan of care. The underlying model for the tool is derived from published guidelines. The model divides the time-sensitive data into risk zones and associates each zone with the appropriate order set for follow-up care. The tool inte...

  18. 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.

  19. "The effect of fluid supplementation on serum bilirubin level during phototerapy in term infants "

    Directory of Open Access Journals (Sweden)

    Torkaman M

    2007-04-01

    Full Text Available Background: Jaundice is a common and benign problem in neonatal period. Several therapeutic procedures for decreasing of serum bilirubin level has been recommended. phototherapy is most common them. Our goal Form this study is the evaluation of serum therapy effects in decreasing of serum bilirubin concentration in icteric infants that are treated with phototherapy. Methods: This is a prospective clinical trial in Najmeih Hospital in 2002. In this study 80 term icteric infants with bilirubin level greater than 17 mg/dl were randomized in two groups, both groups underwent phototherapy and in the case group intravenous fluid supplementation was added. There were no significant differences in the mean gestational age, birth weight, hemoglobin, and also in total serum bilirubin level at admission in the two groups. Results: There were no significant differences in the mean rate of of serum bilirubin level decline during first 24 and 48 hours of hospitalization and also the time of bilirubin decreasing to less than 15 mg/dl and the length of hospitalization in two groups. Conclution: Our study showed intravenous fluid supplementation could be limited to special cases of neonatal icter such as moderate to severe dehydration.

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

    Science.gov (United States)

    Levitt, David G; Levitt, Michael D

    2014-01-01

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

  1. 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. PMID:26408227

  2. 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:

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

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

    2016-01-01

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

  4. 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.

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

    Science.gov (United States)

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

    2016-06-01

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

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

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    Maria do Sameiro-Faria

    2014-01-01

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

  7. STUDY TO PREDICT NEWBORN AT RISK OF DEVELOPING NEONATAL HYPERBILIRUBINAEMIA BY MEASURING CORD BLOOD BILIRUBIN

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    Uthaya

    2016-04-01

    Full Text Available BACKGROUND NNH is a common problem in neonates during 1st week of life. Early discharge of healthy-term newborn is a common practice and NNH is a cause for readmission in most babies. Our aim was to predict the risk of NNH using cord bilirubin values. METHODS Around 150 intramurally delivered healthy term neonates were prospectively enrolled. Cord bilirubin and serum bilirubin at or after 72 hours were estimated. RESULTS AND DISCUSSION Using statistical analysis SPSS 19.0.2 program for windows, significant hyperbilirubinaemia was found in 14% of the neonates. Using cord bilirubin >2 mg/dL, significant hyperbilirubinaemia can be predicted with sensitivity of 90.4%, specificity of 75.1%, PPV of 37.2%, NPV of 97.9% and a p value of <0.05. CONCLUSION A high NPV in our study suggests that healthy term babies with cord bilirubin <2 mg/dL can be discharged early with assurance to parents.

  8. Physiological antioxidative network of the bilirubin system in aging and age-related diseases

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    Sung Young eKim

    2012-03-01

    Full Text Available Oxidative stress is detrimental to life processes and is particularly responsible for aging and age-related diseases. Thus, most organisms are well equipped with a spectrum of biological defense mechanisms against oxidative stress. The major efficient antioxidative mechanism is the glutathione system, operating a redox cycling mechanism for glutathione utilization, which consists of glutathione and its peroxidase and reductase. However, this system is mainly effective for hydrophilic oxidants, while lipophilic oxidants require another scavenging system. Since many age-related pathological conditions are related to lipid peroxidation, especially in association with the aging process, the physiological role of the scavenging system for lipophilic oxidants should be considered. In this regard, the biliverdin to bilirubin conversion pathway, via biliverdin reductase, is suggested to be another major protective mechanism that scavenges lipophilic oxidants because of the lipophilic nature of bilirubin. The efficiency of this bilirubin system might be potentiated by operation of the intertwined bicyclic systems of the suggested redox metabolic cycle of biliverdin and bilirubin and the transcriptional control cycle of biliverdin reductase and heme oxygenase-1. In order to combat oxidative stress, both anti-oxidative systems, against hydrophilic and lipophilic oxidants, respectively, are required to work cooperatively. In this regard, the roles of the bilirubin system in aging and age-related diseases are reassessed in this review, and their interacting networks are evaluated.

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

    Science.gov (United States)

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

    2014-01-01

    Severe neonatal hyperbilirubinemia can be prevented by screening for neonatal jaundice. Transcutaneous bilirubin (TcB) measurement is a noninvasive method for screening neonates. The aim of this study was to examine the correlation between TcB measurement (using the JM-103 bilirubinometer) and total serum bilirubin (TSB) measurement. To our knowledge, this is the first study evaluating the usefulness of the JM-103 bilirubinometer in Turkish neonates. Two hundred and fifty healthy infants in our well-baby nurseries and follow-up clinic with a gestational age of ≥36 weeks who were ≤15 days old were enrolled in this study. TcB measurements were taken usinng the JM-103; almost simultaneously, TSB was checked using a spectrophotometric method. The mean±SD TSB level was 11.2±4.6 mg/dl (range, 0.9-27.0 mg/dl); 17.2% of cases had TSB>15 mg/dl. There was good correlation between transcutaneous bilirubin and total serum bilirubin measurements (Pearson's correlation coefficient 0.87 for TcB from the forehead, 0.88 for TcB from the sternum; pjaundiced infants that require a serum bilirubin check and may reduce the need for TSB measurements. PMID:26388591

  10. Lipopolysaccharide exposure during late embryogenesis results in diminished locomotor activity and amphetamine response in females and spatial cognition impairment in males in adult, but not adolescent rat offspring.

    Science.gov (United States)

    Batinić, Bojan; Santrač, Anja; Divović, Branka; Timić, Tamara; Stanković, Tamara; Obradović, Aleksandar Lj; Joksimović, Srđan; Savić, Miroslav M

    2016-02-15

    Numerous basic and epidemiological studies have connected prenatal maternal immune activation with the occurrence of schizophrenia and/or autism. Depending on subtle differences in protocols of the used animal model, a variety of behavioral abnormalities has been reported. This study investigated behavioral differences in Wistar rat offspring of both genders, exposed to the 100 μg/kg per day dose of lipopolysaccharide (LPS) in late embryogenesis (embryonic days 15 and 16), while tested at their adolescent and young adult age (postnatal days 40 and 60, respectively). Immune activation was confirmed by detecting high levels of TNF-α and IL-6 in dam blood withdrawn 2h after the first dose of LPS. The animals were assessed in three consecutive trials of locomotor activity (novelty exploration, response to i.p. saline injection and challenge with 0.5mg/kg amphetamine), Morris water maze and social interaction tests. Overt behavioral dysfunction was perceived in adult rats only, and these changes were gender-distinctive. When compared with control rats, LPS females displayed baseline hypolocomotion and a decreased reactivity to amphetamine, while LPS males exhibited spatial learning (acquisition trials) and memory (probe trial) impairments. Prenatal treatment did not affect the time spent in social interaction. As maternal exposure to LPS in late gestation resulted in behavioral changes in offspring in early adulthood, it may model schizophrenia-like, but not autism-like endophenotypes. However, lack of a potentiated response to amphetamine testified that this model could not mimic positive symptoms, but rather certain traits of cognitive dysfunction and deficit symptoms, in males and females, respectively. PMID:26620494

  11. A Combination Supplement of Fructo- and Xylo-Oligosaccharides Significantly Abrogates Oxidative Impairments and Neurotoxicity in Maternal/Fetal Milieu Following Gestational Exposure to Acrylamide in Rat.

    Science.gov (United States)

    Krishna, Gokul; Divyashri, Gangaraju; Prapulla, S G; Muralidhara

    2015-09-01

    Prebiotic oligosaccharides are demonstrated to confer a wide spectrum of physiological benefits during pregnancy. In view of this, focused attempts are being directed towards understanding their role as modulators of brain chemistry and behavior. Epidemiological studies have identified that exposure to neurotoxins during prenatal/early life can profoundly impact neurodevelopment/function. In this context, we have tested the hypothesis that a combination of prebiotic supplements during gestation has the propensity to attenuate acrylamide (ACR) induced oxidative impairments, mitochondrial dysfunction and neurotoxicity in maternal and fetal brain of rats. To achieve this, pregnant dams given oral supplements of a combination of fructo- and xylooligosaccharides (FOS + XOS, 3 g/kg/day) during gestation days (GD 0-19) were exposed to ACR (200 ppm in drinking water, GD 6-19). The behavioral analysis revealed that ACR dams fed prebiotics displayed higher exploratory behavior in the open field test. The prenatal evaluation showed that ACR-induced decrements of placental/fetal weights were markedly restored with prebiotic feeding. Prebiotics significantly offset markers of oxidative stress, restored enzymic antioxidants, cholinergic and mitochondrial function in the maternal and fetal brain. Concomitantly, prebiotics restored ACR-induced depletion in the levels of dopamine and γ-aminobutyric acid in the maternal cortex that positively correlated with cecal bacterial numbers. Collectively, these data suggest that prenatal prebiotic oligosaccharide supplements protect developing brain against oxidative stress-mediated neurotoxicity. While the underlying mechanism/s by which prebiotics abrogate the impact of neurotoxicants in the developing brain merits further studies, we speculate that it may be mediated predominantly through attenuation of oxidative stress and proliferation of enteric microbiota. PMID:26248513

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

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    Levitt DG

    2014-09-01

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

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

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    Silvia eGazzin

    2012-05-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

  15. 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

  16. 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

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

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    Christian V Hulzebos

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

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

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    Tanujjal Bora

    2013-11-01

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

  19. Combined effects of smoking and bilirubin levels on the risk of lung cancer in Korea: the severance cohort study.

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    Jung-Eun Lim

    Full Text Available BACKGROUND: Smoking is a major risk factor for lung cancer. Bilirubin, an antioxidant, is inversely associated with the risk of diseases related to oxidative stress. This study was conducted to determine the influence of smoking and bilirubin levels on the risk of lung cancer in the Severance cohort study. METHODS: This study included 68,676 Korean who received a health examination at Severance Health Promotion Center from 1994 to 2004. Serum bilirubin measurements within normal range were divided into tertiles whereas smoking states were divided as never-smokers, former smokers and current smokers. A diagnosis of lung cancer was coded as occurring based on the report from the National Cancer Registry. Hazard ratios (HRs and 95% confidence intervals (95% CIs were calculated using Cox proportional hazards model. RESULTS: At the end of the study period, 240 patients (men: 181, women: 59 developed lung cancer. Compared to those with bilirubin levels ≥ 1.0 mg/dL, HRs (95% CI for lung cancer were 2.8 (1.8-4.2 for subjects having bilirubin levels from 0.2 to 0.7 mg/dL in men. When we stratified our analysis by smoking status, bilirubin consistently showed a protective effect on the risk of lung cancer on both never- and current smokers. Current smokers having bilirubin levels from 0.2 to 0.7 mg/dL had a risk of lung cancer by 6.0-fold higher than never-smokers with bilirubin levels ≥ 1.0 mg/dL in men. CONCLUSION: In this large prospective study, higher baseline bilirubin level in the normal range was associated with low risk of lung cancer. Smoking and low bilirubin levels were cumulatively associated with a higher risk of lung cancer.

  20. Profile of Minocycline Neuroprotection in Bilirubin-Induced Auditory System Dysfunction

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    Rice, Ann C.; Chiou, Victoria; Zuckoff, Sarah B; Shapiro, Steven M

    2010-01-01

    Excessive hyperbilirubinemia in human neonates can cause permanent dysfunction of the auditory system, as assessed with brainstem auditory evoked potentials (BAEPs). Jaundiced Gunn rat pups (jjs) exhibit similar BAEP abnormalities as hyperbilirubinemic neonates. Sulfadimethoxine (sulfa) administration to jjs, which displaces bilirubin from serum albumin into tissues including brain, exacerbates acute toxicity. Minocycline administered prior to sulfa in jjs protects against BAEP abnormalities....

  1. 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...

  2. 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

  3. 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.

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

    NARCIS (Netherlands)

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

    2015-01-01

    Circulating bilirubin, a natural antioxidant, is associated with decreased risk of type 2 diabetes (T2D), but the nature of the relationship remains unknown. We performed Mendelian randomization in a prospective cohort of 3,381 participants free of diabetes at baseline (aged 28-75 years; women, 52.6

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

    Science.gov (United States)

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

    1994-05-01

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

  6. 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.

  7. 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 UA concentrations were also lower than the controls (P IBIL = 0.013, P UA = 0.000). Although IBIL concentration was positively correlated with UA concentration in controls (R IBIL = 0.229, P IBIL = 0.004), this positive association was not observed in the PD group (R IBIL = -0.032, P IBIL = 0.724). Decreased levels of serum IBIL and UA were observed in PD patients. It is possible that individuals with decreased serum 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.

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

    Science.gov (United States)

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

    2016-01-01

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

  9. 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.

  10. 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.

  11. 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

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

    Science.gov (United States)

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

    2015-11-16

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

  13. Ionization of tyrosine residues in human serum albumin and in its complexes with bilirubin and laurate

    DEFF Research Database (Denmark)

    Honoré, B; Brodersen, R

    1992-01-01

    .7, and in the bilirubin-albumin complex between pH 11.2 and 11.7 with a Hill coefficient 1.6. With a stopped-flow technique it is shown that about seven of the tyrosines ionize fast, with rate constants well above 10(2) s-1, when pH is suddenly changed from near neutral to pH 11.76. Further residues ionize slowly......, with rate constants around 10(2) s-1 or less. The N-form of albumin (pH 6) contains one more fast ionizing tyrosine than the B-form of albumin (pH 10). Binding of bilirubin or laurate to the albumin molecule (molar ratio 1:1) transforms one to three of the fast ionizing tyrosines to slowly ionizing...

  14. 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.

  15. 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.

  16. Safety and pharmacology of paclitaxel in patients with impaired liver function : a population pharmacokinetic-pharmacodynamic study

    NARCIS (Netherlands)

    Joerger, M.; Huitema, A. D. R.; Huizing, M. T.; Willemse, P. H. B.; Rosing, H.; Schellens, J. H. M.; Beijnen, J. H.; Vermorken, J. B.

    2007-01-01

    Aims To assess quantitatively the safety and pharmacology of paclitaxel in patients with moderate to severe hepatic impairment. Methods Solid tumour patients were enrolled into five liver function cohorts as defined by liver transaminase and total bilirubin concentrations. Paclitaxel was administere

  17. Effect of Intravenous Fluid Supplementation on Serum Bilirubin Level in Jaundiced Healthy Neonates during Conventional Phototherapy

    OpenAIRE

    R.Iranpour; R Nohekhan; I Haghshenas

    2004-01-01

    Background: Adequate hydration and good urine output improve the efficacy of phototherapy. The aim of this study was to evaluate the effect of intravenous fluid supplementation on decrease of serum bilirubin levels in jaundiced healthy term infants during conventional phototherapy. Methods: Sixty healthy breast-fed neonates with non-hemolytic hyperbilirubinemia were assigned randomly to receive either breast milk exclusively (non-supplemented group; n=30) or intravenous fluid in addition to b...

  18. The Effect of Clofibrate on Decreasing Serum Bilirubin in Healthy Term Neonates under Home Phototherapy

    OpenAIRE

    Simin Sharafi; Zhaleh Mortazavi; Reza Sharafi; Reza Moradi Parashkouh

    2010-01-01

    Objective: this study was designed to determine the effect of clofibrate on neonatal uncomplicated jaundice treated with home phototherapy. Methods:This clinical trial study was performed on 60 newborns with jaundice that received home phototherapy. Inclusion criteria were body weight between 2500 to 4000 gr, breastfed, total serum bilirubin (TSB) between 14 to 20 mg/dl, aged over 72 hours. The neonates were randomly divided into two groups. All received home phototherapy. Group i received a ...

  19. 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.

  20. 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.

  1. Bilirubin influence on oxidative lung damage and surfactant surface tension properties

    OpenAIRE

    Dani C.; Martelli E.; Tronchin M.; Buonocore G.; Longini M.; Di Filippo A; Giossi M.; Rubaltelli F.F.

    2004-01-01

    To study the hypothesis that hyperbilirubinemia might reduce in vivo oxidative lung damage while also diminishing lung surfactant surface tension properties during acute lung injury, we performed a randomized study in a rabbit model of acute lung injury. Twenty rabbits were randomized to receive bilirubin or saline intravenously. Acute lung injury was induced by lung lavages with saline. Lung tissue oxidation was evaluated by measuring total hydroperoxide (TH), advanced oxidation protein prod...

  2. Effect of Intravenous Fluid Supplementation on Serum Bilirubin Level in Jaundiced Healthy Neonates during Conventional Phototherapy

    Directory of Open Access Journals (Sweden)

    R Iranpour

    2004-08-01

    Full Text Available Background: Adequate hydration and good urine output improve the efficacy of phototherapy. The aim of this study was to evaluate the effect of intravenous fluid supplementation on decrease of serum bilirubin levels in jaundiced healthy term infants during conventional phototherapy. Methods: Sixty healthy breast-fed neonates with non-hemolytic hyperbilirubinemia were assigned randomly to receive either breast milk exclusively (non-supplemented group; n=30 or intravenous fluid in addition to breast milk (supplemented group; n=30 during conventional phototherapy. Results: The mean total serum bilirubin (TSB levels at the time of enrollment and within 84 hours after phototherapy were not statistically different between two groups. Similarly, the mean rate of decrease in TSB levels during the first 12 h of phototherapy were 0.13±0.06 and 0.10 ± 0.1 mg/dL/h in supplemented and non supplemented groups , respectively (P=0.13. Duration of phototherapy required in supplemented and non-supplemented groups was 58 ± 13.02 and 63.20 ± 13.71 hours, respectively (P=0.13. Conclusion: These data show that administration of extra intravenous fluid in jaundiced healthy, term, breastfed neonates have no beneficial effect on the rate of serum bilirubin reduction during conventional phototherapy. Keywords: Hyperbilirubinemia, Phototherapy, Neonates, Fluid Supplementation, Dehydration.

  3. 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...

  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. Fluorescence Excitation Spectrum of Bilirubin in Blood: A Model for the Action Spectrum for Phototherapy of Neonatal Jaundice†

    OpenAIRE

    Lamola, Angelo A.; Russo, Marie

    2013-01-01

    A recent report (Lamola et al. 2013 Pediatric Research, 74, 54–60) presents a semi-empirical model for facile calculation of an action spectrum for bilirubin photochemistry in vivo using the most current knowledge of the optics of neonatal skin. The calculations indicate that competition for phototherapy light by hemoglobin in the skin is the predominant factor that defines the spectrum of light absorbed by bilirubin. If the latter is correct, a valid physical analog of the calculated spectru...

  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. PMID:26834549

  7. 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.

  8. 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.

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

    International Nuclear Information System (INIS)

    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 μg/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

  10. Impaired Driving

    Science.gov (United States)

    ... help prevent injuries and deaths from alcohol-impaired driving. The Problem Risk Factors BAC Effects Prevention Additional Resources How big is the problem? In 2014, 9,967 people were killed in alcohol-impaired driving crashes, accounting for nearly one-third (31%) of ...

  11. Decreased Hippocampal 5-HT and DA Levels Following Sub-Chronic Exposure to Noise Stress: Impairment in both Spatial and Recognition Memory in Male Rats

    OpenAIRE

    Haider, Saida; Naqvi, Fizza; Batool, Zehra; Tabassum, Saiqa; Perveen, Tahira; Saleem, Sadia; Haleem, Darakhshan Jabeen

    2012-01-01

    Mankind is exposed to a number of stressors, and among them noise is one which can cause intense stress. High levels of background noise can severely impair one’s ability to concentrate. The present study was aimed to investigate the effect of sub-chronic noise stress on cognitive behavior and hippocampal monoamine levels in male rats. The study was performed on 12 male Wistar rats, divided into two groups; the control and noise-exposed. The rats in the test group were subjected to noise stre...

  12. 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

  13. 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

  14. 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.

  15. 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.

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

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    Eun Sook Kim

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

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

    Science.gov (United States)

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

    2015-04-01

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

  18. 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

    OpenAIRE

    Luis Moya-Albiol; Williams, Ryan K.; Marisol Lila; Alba Catalá-Miñana; Ángel Romero-Martínez

    2013-01-01

    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 perpetra...

  19. Exposure in utero to 2,2',3,3',4,6'-hexachlorobiphenyl (PCB 132) impairs sperm function and alters testicular apoptosis-related gene expression in rat offspring

    International Nuclear Information System (INIS)

    Toxicity of the polychlorinated biphenyls (PCBs) depends on their molecular structure. Mechanisms by prenatal exposure to a non-dioxin-like PCB, 2,2',3,4',5',6-hexachlorobiphenyl (PCB 132) that may act on reproductive pathways in male offspring are relatively unknown. The purpose was to determine whether epididymal sperm function and expression of apoptosis-related genes were induced or inhibited by prenatal exposure to PCB 132. Pregnant rats were treated with a single dose of PCB 132 at 1 or 10 mg/kg on gestational day 15. Male offspring were killed and the epididymal sperm counts, motility, velocity, reactive oxygen species (ROS) generation, sperm-oocyte penetration rate (SOPR), testicular histopathology, apoptosis-related gene expression and caspase activation were assessed on postnatal day 84. Prenatal exposure to PCB 132 with a single dose of 1 or 10 mg/kg decreased cauda epididymal weight, epididymal sperm count and motile epididymal sperm count in adult offspring. The spermatozoa of PCB 132-exposed offspring produced significantly higher levels of ROS than the controls; ROS induction and SOPR reduction were dose-related. In the low-dose PCB 132 group, p53 was significantly induced and caspase-3 was inhibited. In the high-dose group, activation of caspase-3 and -9 was significantly increased, while the expressions of Fas, Bax, bcl-2, and p53 genes were significantly decreased. Gene expression and caspase activation data may provide insight into the mechanisms by which exposure to low-dose or high-dose PCB 132 affects reproduction in male offspring in rats. Because the doses of PCB 132 administered to the dams were approximately 625-fold in low-dose group and 6250-fold higher in high-dose group than the concentration in human tissue levels, the concentrations are not biologically or environmentally relevant. Further studies using environmentally relevant doses are needed for hazard identification

  20. 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

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

    OpenAIRE

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

    2014-01-01

    We evaluated the potential cardiovascular risk protection of bilirubin in hemodialysis (HD) patients. An enlarged set of studies were evaluated in 191 HD patients, including hematological study, lipid profile, iron metabolism, nutritional, inflammatory markers, and dialysis adequacy. The TA duplication screening in the UDP-glucuronosyltransferase 1 A1 (UGT1A1) promoter region was also performed. The UGT1A1 genotype frequencies in HD patients were 49.2%, 42.4%, and 8.4% for 6/6, 6/7, and 7/7 g...

  2. 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

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

    OpenAIRE

    Go Miyano; Hiroki Nakamura; Toshiaki Takahashi; Lane, Geoffrey J.; Atsuyuki Yamataka

    2013-01-01

    Background: The aim of our study was to investigate if total bilirubin (T-bil), amylase (Amy), and sodium (Na) in nasogastric (NG) aspirates can reflect gastrointestinal motility reliably. Materials and Methods: NG aspirates from all laparotomies lasting more than 150 min in children less than 12 months old were studied for 3 months. Color of aspirates and intensity of bowel sounds were graded every 3 h by nursing staff and aspirate samples for measuring T-bil, Amy, and Na were collected inde...

  4. 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.

  5. Daily Exposure to Sucrose Impairs Subsequent Learning About Food Cues: A Role for Alterations in Ghrelin Signaling and Dopamine D2 Receptors.

    Science.gov (United States)

    Sharpe, M J; Clemens, K J; Morris, M J; Westbrook, R F

    2016-04-01

    The prevalence of hedonic foods and associated advertising slogans has contributed to the rise of the obesity epidemic in the modern world. Research has shown that intake of these foods disrupt dopaminergic systems. It may be that a disruption of these circuits produces aberrant learning about food-cue relationships. We found that rodents given 28 days of intermittent access to sucrose exhibited a deficit in the ability to block learning about a stimulus when it is paired in compound with food and another stimulus that has already been established as predictive of the food outcome. This deficit was characterized by an approach to a cue signaling food delivery that is usually blocked by prior learning, an effect dependent on dopaminergic prediction-error signaling in the midbrain. Administering the D2 agonist quinpirole during learning restored blocking in animals with a prior history of sucrose exposure. Further, repeated central infusions of ghrelin produced a deficit in blocking in the same manner as sucrose exposure. We argue that changes in dopaminergic systems resulting from sucrose exposure are mediated by a disruption of ghrelin signaling as rodents come to anticipate delivery of the highly palatable sucrose outside of normal feeding schedules. This suggestion is supported by our finding that both sucrose and ghrelin treatments resulted in increases in amphetamine-induced locomotor responding. Thus, for the first time, we have provided evidence of a potential link between alterations in D2 receptors caused by the intake of hedonic foods and aberrant learning about cue-food relationships capable of promoting inappropriate feeding habits. In addition, we have found preliminary evidence to suggest that this is mediated by changes in ghrelin signaling, a finding that should stimulate further research into modulation of ghrelin activity to treat obesity. PMID:26365954

  6. The predictive value of first day bilirubin levels for early discharged newborns.

    Directory of Open Access Journals (Sweden)

    MUSTAFA TOLGA ÜNSÜR

    2015-09-01

    Full Text Available Objective: Early discharge of newborns is essential because of social, economic an medical reasons in our area, but it increases readmission rates especially for hyperbilirubinemia. Hence, predicting the high risk neonates for subsequent hyperbilirubinemia is required. This study was designed to investigate which level of total serum bilirubin (TSB at the first day could be used to predict hyperbilirubinemia .Methods: The venous blood samples obtained from 300 newborns at post-partum 24±6 hours for blood group, direct coomb’s, TSB and direct bilirubin level (DBL. These newborns were followed up during 5- day and TSB and DBLwere detected in 90 newborns with jaundice again according to Kramer dermal zones at 120±6 hours of age.Results: In 23.3% of 90 newborns phototherapy was needed. The cut off value of TSB at the first day to define newborns at high risk for subsequent hyperbilirubinemia was 6.50 mg/dl with positive predictive value 19.75%, negative predictive value 97.72%. At that point sensitivity was 76.19%, specificity was 76.70%.Conclusion: The cut-off point of 6.5 mg/dl of TSB at the first day might be used to predict subsequent hyperbilirubinemia risk at healthy, full-term early discharged newborns as the test is economic and available in all healthcare units.

  7. 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.

  8. 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).

  9. 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.

  10. 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.

  11. Short-term exposure to a diet high in fat and sugar, or liquid sugar, selectively impairs hippocampal-dependent memory, with differential impacts on inflammation.

    Science.gov (United States)

    Beilharz, J E; Maniam, J; Morris, M J

    2016-06-01

    Chronic high-energy diets are known to induce obesity and impair memory; these changes have been associated with inflammation in brain areas crucial for memory. In this study, we investigated whether inflammation could also be related to diet-induced memory deficits, prior to obesity. We exposed rats to chow, chow supplemented with a 10% sucrose solution (Sugar) or a diet high in fat and sugar (Caf+Sugar) and assessed hippocampal-dependent and perirhinal-dependent memory at 1 week. Both high-energy diet groups displayed similar, selective hippocampal-dependent memory deficits despite the Caf+Sugar rats consuming 4-5 times more energy, and weighing significantly more than the other groups. Extreme weight gain and excessive energy intake are therefore not necessary for deficits in memory. Weight gain across the diet period however, was correlated with the memory deficits, even in the Chow rats. The Sugar rats had elevated expression of a number of inflammatory genes in the hippocampus and WAT compared to Chow and Caf+Sugar rats but not in the perirhinal cortex or hypothalamus. Blood glucose concentrations were also elevated in the Sugar rats, and were correlated with the hippocampal inflammatory markers. Together, these results indicate that liquid sugar can rapidly elevate markers of central and peripheral inflammation, in association with hyperglycemia, and this may be related to the memory deficits in the Sugar rats. PMID:26970578

  12. 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. PMID:26774980

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

    Science.gov (United States)

    Lamola, Angelo A; Russo, Marie

    2014-01-01

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

  14. 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.

  15. 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.

  16. 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.

  17. Nutrient digestibility and growth in rainbow trout (Oncorhynchus mykiss) are impaired by short term exposure to moderate supersaturation in total gas pressure

    DEFF Research Database (Denmark)

    Skov, Peter Vilhelm; Pedersen, Lars-Flemming; Pedersen, Per Bovbjerg

    2013-01-01

    maintained at or above saturation, this leads to a supersaturation in total gas pressure (TGP). Depending on severity, total gas pressures above saturation may lead to gas bubble trauma, evident by visual inspection of the fish. Physiological effects of subclinical levels of TGP are not well known and have...... not been investigated for rainbow trout. The present study examined the effects of N2 supersaturation, with or without simultaneous excess TGP. Supersaturation with N2 (ΔP 22mmHg) without total gas supersaturation (ΔTGP −6mmHg) did not have any significant effects on feed intake, feed conversion or growth....... Short term (16days) exposure to N2 supersaturation (ΔP 36mmHg) in combination with a ΔTGP of 23mmHg did not affect feed intake, nor did it cause GBT or any apparent changes in behaviour. Excess TGP did, however, significantly reduce apparent lipid digestibility, feed conversion, and the thermal growth...

  18. 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

  19. Hearing Impairment

    Science.gov (United States)

    ... hearing loss is present at birth. Acquired hearing loss happens later in life — during childhood, the teen years, or in adulthood — ... for your ears to avoid a permanent hearing loss. See your doctor right away ... basis. What's Life Like for People Who Are Hearing Impaired? For ...

  20. 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.

  1. 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. PMID:26708410

  2. 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

  3. The Effect of Clofibrate on Decreasing Serum Bilirubin in Healthy Term Neonates Under Home Phototherapy

    Directory of Open Access Journals (Sweden)

    Simin Sharafi

    2010-03-01

    Full Text Available Objective: this study was designed to determine the effect of clofibrate on neonatal uncomplicated jaundice treated with home phototherapy. Methods:This clinical trial study was performed on 60 newborns with jaundice that received home phototherapy. Inclusion criteria were body weight between 2500 to 4000 gr, breastfed, total serum bilirubin (TSB between 14 to 20 mg/dl, aged over 72 hours. The neonates were randomly divided into two groups. All received home phototherapy. Group i received a single dose of 50 mg/kg clofibrate and the other group served as control group. Total serum bilirubin level was measured every 24 hours. Findings:Two groups were matched regarding weight, sex, age and first TSB. At 24 and 48 hours of treatment, the mean values of TSB in the clofibrate group were 13.72 (1.56, 9.5 (0.56 and in the control group 15.30 (1.44, 12.6 (1.44. The results show that TSB was significantly decreased after 24 and 48 hours in clofibrate group (P<0.001. The mean duration of phototherapy in group I was 72(0.0 hours and in the control group 76.80 (±9.76 hours. The duration of phototherapy was significantly shorter in clofibrate group (P<0.001. Conclusion:Clofibrate is effective for outpatients with neonatal hyperbilirubinemia who are under home phototherapy. Of course, further studies are needed for approved routine use of this drug in the treatment of neonatal jaundice.

  4. [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.

  5. 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

  6. 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 < 0.001) and dBili (3.7 ± 1.0 mg/dl; P < 0.001) than did diseased waterbuck (n = 21; tBili: 4.9 ± 2.56 mg/dl; dBili: 2.2 ± 0.8 mg/dl). No waterbuck had icteric tissues on physical examination. Twelve (19.7%) waterbuck (six healthy, six diseased) had icteric serum. Few minor correlations were seen between tBili or dBili and clinical, laboratory, or necropsy evidence of disease, though an inverse correlation between dBili and blood glucose was noted. Of the 40 healthy animals, reference intervals were calculated for tBili (5.5-10.3 mg/dl), dBili (1.7-5.7 mg/dl), and indirect bilirubin (2.2-6.2 mg/dl). These results suggest healthy waterbuck have relatively high tBili and dBili compared with related species. Icteric serum may be seen in up to 15% of healthy animals in the absence of icteric tissues.

  7. 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.

  8. 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.

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

    Science.gov (United States)

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

    2004-07-01

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

  10. 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.

  11. Theory of the variable quantum yield of Bilirubin-IX Photoisomers: the end of a chapter

    International Nuclear Information System (INIS)

    Full text: Bilirubin-IX (BR-IX), responsible for neonatal jaundice, has two slightly different chromophores which undergo the Davidoff (exciton) interaction. Because of this, BR-IX in certain solvents, e.g. human serum albumin (but not Me/OH) exhibits magnetic circular dichroism (MCD), due to the exciton lines only. The absoption spectrum of BR-IX in the exciton line region is best fitted by two gaussian lines of equal width, but the MCD spectrum best fit requires two gaussian of unequal width: the gaussian assumption is made for ease of calculation. The difference between the fitted spectra shows up as a single broad line of maximum smaller than that of the gaussian lines, and in the region of the central portion of the gaussians overlap. The origin of this line is as yet unknown, so that much further work needs to be done on the structure of the excited state of BR-IX giving rise to the exciton interaction. This is currently being undertaken. However, the variation of the exciton interaction energy with wavelength as deduced from present theory seems reasonably certain though its origin may not be

  12. 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. PMID:19788065

  13. 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. PMID:27267279

  14. 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.

  15. Rapid determination of amphotericin B levels in serum by high-performance liquid chromatography without interference by bilirubin.

    OpenAIRE

    Hosotsubo, H; Takezawa, J; Taenaka, N; Hosotsubo, K; Yoshiya, I

    1988-01-01

    A high-performance liquid chromatographic method for the determination of amphotericin B concentrations in human serum without bilirubin interference was developed and compared with a microbiological assay. The high-performance liquid chromatographic assay utilized a reversed-phase trimethyl silica column, simple sample preparation, and visible detection. Reproducibility studies yielded coefficient-of-variation ranges from 1.02 to 2.11% for within-day precision and 2.88 to 4.32% for between-d...

  16. 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.

  17. Pharmacokinetics and tolerability of cediranib, a potent VEGF signalling inhibitor, in cancer patients with hepatic impairment

    DEFF Research Database (Denmark)

    van Herpen, Carla M L; Lassen, Ulrik; Desar, Ingrid M E;

    2013-01-01

    tumours received a single 45 mg dose of cediranib, followed by 30 mg continuous once-daily oral dosing for 21 days after a 7-day washout period (clinicaltrials.gov identifier NCT00621725). The primary objective was to compare the single-dose pharmacokinetics (PK) of cediranib in patients with different...... levels of hepatic impairment classified according to the bilirubin level. Safety, tolerability, multiple-dose PK and PK stratified according to the Child-Pugh criteria were also assessed. Thirty patients received cediranib: 18 with normal-mild hepatic impairment and 12 with moderate hepatic impairment...... not influence PK results in multiple dosing. After continuous once-daily dosing, the geometric least square means ratio was 0.72 (90% CI 0.51-1.03) for AUCSS and 0.67 (90% CI 0.47-0.94) for CSS,max. Similar results were obtained when patients were classified for hepatic impairment according to the...

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

    Science.gov (United States)

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

    2016-07-01

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

  19. 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. PMID:27126550

  20. 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.

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

    Directory of Open Access Journals (Sweden)

    Go Miyano

    2013-01-01

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

  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. 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

  5. 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

  6. 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

  7. 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...

  8. The Relationship between the Behavioral Hearing Thresholds and Maximum Bilirubin Levels at Birth in Children with a History of Neonatal Hyperbilirubinemia

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    Rasool Panahi

    2013-06-01

    Full Text Available Introduction: Neonatal hyperbilirubinemia is one of the most important factors affecting the auditory system and can cause sensorineural hearing loss. This study investigated the relationship between behavioral hearing thresholds in children with a history of jaundice and the maximum level of bilirubin concentration in the blood.   Materials and Methods: This study was performed on 18 children with a mean age of 5.6 years and with a history of neonatal hyperbilirubinemia. Behavioral hearing thresholds, transient evoked emissions and brainstem evoked responses were evaluated in all children.   Results: Six children (33.3 % had normal hearing thresholds and the remaining (66.7 % had some degree of hearing loss. There was no significant relationship (r= -0.28, P= 0.09 between the mean total bilirubin levels and behavioral hearing thresholds in all samples. A transient evoked emission was seen only in children with normal hearing thresholds however in eight cases brainstem evoked responses had not detected.   Conclusion:  Increased blood levels of bilirubin at the neonatal period were potentially one of the causes of hearing loss. There was a lack of a direct relationship between neonatal bilirubin levels and the average hearing thresholds which emphasizes on the necessity of monitoring the various amounts of bilirubin levels.

  9. 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

  10. A COMPARISON STUDY: CORD SERUM ALBUMIN IS COMPARED WITH CORD SERUM BILIRUBIN AS A RISK INDICATOR IN PREDICTING NEONATAL JAUNDICE

    Directory of Open Access Journals (Sweden)

    Venkatamurthy

    2014-04-01

    Full Text Available : OBJECTIVE: 1. Comparing Cord Serum Albumin level (CSA with Cord Serum Bilirubin (CSB in predicting neonatal hyperbilirubinemia. 2. To know the sensitivity, specificity, Positive predictive value and negative predictive value of CSA and CSB in predicting neonatal jaundice in term neonates. METHOD: Prospective study was performed on 174 healthy term neonates. Relevant maternal history is collected. Cord blood was collected from the healthy term neonates at birth, CSA and CSB measured. Neonate was assessed clinically every day. Total Serum Bilirubin (TSB and blood group were assessed in neonate during 72-96 hours of life. TSB value ≥17mg/dl is considered Neonatal Hyperbilirubinemia (NH which requires intervention like phototherapy (PT or Exchange transfusion (ExT. RESULT: Study cohort is grouped in Group 1, Group 2 and Group 3 based on Cord Serum Albumin level ≤2.8g/dl, 2.9-3.3g/dl and ≥3.4g/dl, respectively. Based on CSB, study cohort divided into neonates with CSB ≤ 2mg/dl and CSB ≥ 2.1mg/dl. Statistical analysis done for correlation of CSA and CSB with NH. Statistical significance is seen for both CSA and CSB. CONCLUSION: Both CSA and CSB are equally effective in predicting NH at birth. These study variables can be considered as neonatal screening tool for NH for term neonates.

  11. Impaired nonspecific cellular immunity in experimental cholestasis.

    Science.gov (United States)

    Roughneen, P T; Drath, D B; Kulkarni, A D; Rowlands, B J

    1987-11-01

    The abilities of polymorphonuclear leukocytes (PMN) and pulmonary alveolar macrophages (PAM), to demonstrate chemotaxis, phagocytosis, and superoxide release after bile duct ligation in the rat were investigated to determine the effect of cholestasis on nonspecific cellular immune mechanisms. Chemotactic response to C5a and FMLP, phagocytosis of 14C labeled Staphylococcus aureus, and zymosan-induced superoxide release were evaluated 21 days after bile duct ligation (BDL), sham operation, or in normal controls. Serum total bilirubin level was elevated after BDL (p less than 0.01). Chemotactic ability was similar to each group. PMN phagocytic uptake of 14C labeled Staphylococcus aureus was depressed in BDL (p less than 0.05). BDL rats exhibited impaired PAM phagocytic indices and improved PMN superoxide release (p less than 0.03). PAM superoxide release was similar in each study group. Alterations in phagocytic function with cholestasis are important deficits in nonspecific cellular immunity that may contribute to the high incidence of infective complications associated with obstructive jaundice. PMID:2823730

  12. 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 < 0.001), alanine transaminase (ALT) from 142 ± 28 to 47.8 ± 16 IU/L (P < 0.05) and serum bilirubin from 2.8 ± 0.50 to 1.24 ± 0.30 mg/dl (P < 0.05). Treatment with Lip-TQ reduced the CYP-induced inflammation and hemorrhage in liver tissues. Moreover, treatment with free or Lip-TQ protected the activity of SOD and CAT in CYP-injected mice. Therefore, TQ can reduce the level of bilirubin in systemic circulation in disease conditions that lead to hyperbilirubinemia and liver toxicity and hence may be used as a supplement in the treatment of liver ailments. PMID:27265787

  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. 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

  15. 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%.

  16. 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.

  17. 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).

  18. 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.

  19. 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.

  20. Visual impairment in the hearing impaired students

    Directory of Open Access Journals (Sweden)

    Gogate Parikshit

    2009-01-01

    Full Text Available Background : Ocular problems are more common in children with hearing problems than in normal children. Neglected visual impairment could aggravate educational and social disability. Aim : To detect and treat visual impairment, if any, in hearing-impaired children. Setting and Design : Observational, clinical case series of hearing-impaired children in schools providing special education. Materials and Methods : Hearing-impaired children in selected schools underwent detailed visual acuity testing, refraction, external ocular examination and fundoscopy. Ocular motility testing was also performed. Teachers were sensitized and trained to help in the assessment of visual acuity using Snellen′s E charts. Refractive errors and squint were treated as per standard practice. Statistical Analysis : Excel software was used for data entry and SSPS for analysis. Results : The study involved 901 hearing-impaired students between four and 21 years of age, from 14 special education schools. A quarter of them (216/901, 24% had ocular problems. Refractive errors were the most common morbidity 167(18.5%, but only 10 children were using appropriate spectacle correction at presentation. Fifty children had visual acuity less than 20/80 at presentation; after providing refractive correction, this number reduced to three children, all of whom were provided low-vision aids. Other common conditions included strabismus in 12 (1.3% children, and retinal pigmentary dystrophy in five (0.6% children. Conclusion : Ocular problems are common in hearing-impaired children. Screening for ocular problems should be made mandatory in hearing-impaired children, as they use their visual sense to compensate for the poor auditory sense.

  1. 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

  2. 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

  3. 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

  4. 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.

  5. 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.

  6. Depression in Cognitive Impairment

    Science.gov (United States)

    Pellegrino, Laurel D.; Lyketsos, Constantine G.; Marano, Christopher M.

    2014-01-01

    Depression and cognitive disorders, including dementia and mild cognitive impairment, are common in the elderly. Depression is also a common feature of cognitive impairment although the symptoms of depression in cognitive impairment differ from depression without cognitive impairment. Pre-morbid depression approximately doubles the risk of subsequent dementia. There are two predominant, though not mutually exclusive, constructs linking pre-morbid depression to subsequent cognitive impairment: Alzheimer’s pathology and the vascular depression hypothesis. When evaluating a patient with depression and cognitive impairment, it is important to obtain caregiver input and to evaluate for alternative etiologies for depressive symptoms such as delirium. We recommend a sequential approach to the treatment of depression in dementia patients: (1) a period of watchful waiting for milder symptoms, (2) psychosocial treatment program, (3) a medication trial for more severe symptoms or failure of psychosocial interventions, and (4) possible ECT for refractory symptoms. PMID:23933974

  7. 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...

  8. 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…

  9. 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

  10. 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

  11. 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。

  12. Emotion-Induced Amnesia in Rats: Working Memory-Specific Impairment, Corticosterone-Memory Correlation, and Fear Versus Arousal Effects on Memory

    OpenAIRE

    Woodson, James C.; Macintosh, Deric; Fleshner, Monika; Diamond, David M

    2003-01-01

    We have shown previously that psychological stress (predator exposure) impairs spatial memory in rats. We have extended that finding here to show that predator stress selectively impaired recently acquired (hippocampal-dependent) spatial working memory without affecting long-term (hippocampal-independent) spatial reference memory. We also investigated why predator exposure impairs memory. Was spatial memory impaired because of the fear-provoking aspects of predator exposure or only because th...

  13. Criteria for driver impairment

    NARCIS (Netherlands)

    Brookhuis, K.A.; De Waard, D.; Fairclough, S.H

    2003-01-01

    Most traffic accidents can be attributed to driver impairment, e.g. inattention, fatigue, intoxication, etc. It is now technically feasible to monitor and diagnose driver behaviour with respect to impairment with the aid of a limited number of in-vehicle sensors. However, a valid framework for the e

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

    Directory of Open Access Journals (Sweden)

    Rupali Rakshit

    2015-11-01

    Full Text Available 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.

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

    Science.gov (United States)

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

    2016-08-01

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

  16. 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

    OpenAIRE

    Mahmoud A.F. Kaabneh; Ghassan S. A. Salama; Ayoub G.A Shakkoury; Ibrahim M. H. Al-abdallah; Afrah Alshamari; Ruba A.A. Halaseh

    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 di...

  17. 新生儿胆红素脑病43例临床分析%Clinical Analysis of 43 Cases With Neonatal Bilirubin Encephalopathy

    Institute of Scientific and Technical Information of China (English)

    刘向红; 郎玉洁

    2015-01-01

    目的:了解胆红素脑病的病因及后遗症的发生情况,重视胆红素脑病的早期诊断、早期干预。方法43例胆红素脑病患儿进行病因、辅助检查、治疗、转归及随访结果进行分析研究。结果胆红素脑病的病因主要为感染占46.5%(23/43),出血占34.9%(15/43)和溶血占18.6%(8/43),后遗症的发生率为40.6%。结论应早期就诊,针对病因综合积极治疗,可减少智力落后、脑瘫等后遗症的发生。%Objective To investigate the etiology and the sequelae of bilirubin encephalopathy,pay attention to early diagnosis and early intervention of neonatal bilirubin encephalopathy.Methods 43 cases of bilirubin encephalopathy etiology,auxiliary examination,treatment,prognosis and folow-up results were analyzed.ResultsThe causes of bilirubin encephalopathy were mainly infection accounted for 46.5%(23/43),hemorrhage accounted for 34.9%(15/43)and hemolysis accounted for 18.6%(8/43),the incidence of sequelae rate was 40.6%.Conclusion Early treatment,comprehensive treatment for the cause,and can reduce mental retardation,cerebral palsy sequela.

  18. Development and validation of serum bilirubin nomogram to predict the absence of risk for severe hyperbilirubinaemia before discharge: a prospective, multicenter study

    OpenAIRE

    Romagnoli Costantino; Tiberi Eloisa; Barone Giovanni; De Curtis Mario; Regoli Daniela; Paolillo Piermichele; Picone Simonetta; Anania Stefano; Finocchi Maurizio; Cardiello Valentina; Giordano Lucia; Paolucci Valentina; Zecca Enrico

    2012-01-01

    Abstract Background Early discharge of healthy late preterm and full term newborn infants has become common practice because of the current social and economic necessities. Severe jaundice, and even kernicterus, has developed in some term infants discharged early. This study was designed to elaborate a percentile-based hour specific total serum bilirubin (TSB) nomogram and to assess its ability to predict the absence of risk for subsequent non physiologic severe hyperbilirubinaemia before dis...

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

    OpenAIRE

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

    2014-01-01

    OBJECTIVE: to prospectively validate a previously constructed transcutaneous bilirubin (TcB) nomogram for identifying severe hyperbilirubinemia in healthy Chinese term and late-preterm infants. METHODS: this was a multicenter study that included 9,174 healthy term and late-preterm infants in eight hospitals of China. TcB measurements were performed using a JM-103 bilirubinometer. TcB values were plotted on a previously developed TcB nomogram, to identify the predictive ability for subseq...

  20. 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

  1. 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...

  2. 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.

  3. 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.

  4. 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

  5. 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

  6. Speech impairment (adult)

    Science.gov (United States)

    ... brain tumors or degenerative diseases that affect the language areas of the brain. This term does not apply to children who ... gradually, but anyone can develop a speech and language impairment ... Brain tumor (more common in aphasia than dysarthria) Dementia ...

  7. 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 ...

  8. Aids for visual impairment.

    OpenAIRE

    Dudley, N. J.

    1990-01-01

    This article provides only a flavour of the type and range of aids available to the visually impaired person. Many other aids for leisure, learning, and daily living are illustrated in the RNIB equipment and games catalogue.

  9. Kids' Quest: Vision Impairment

    Science.gov (United States)

    ... and neighborhood . Step 8: Now see if your attitudes have changed. Take the Fact Checkup again. ... impairment also have at least one other developmental disability, such as intellectual disabilities, cerebral palsy, hearing loss, ...

  10. 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 somatic mutant frequency in the hypoxanthine-guanine phosphoribosyl-transferase (HPRT) gene in human lymphocytes and the glycophorin A (GPA) gene of red blood cells (both N0, NN mutants), and the frequency of lymphocyte micronuclei (both kinetochore (K) positive or micronuclei K negative) in 101 healthy smoking and nonsmoking individuals. As hypothesized, genotypes containing 7-TA and 8-TA displayed marginally lower GPA{_}NN mutant frequency relative to 5/5, 5/6, 6/6 genotypes (p<0.05). In contrast, our analysis showed that lower expressing UGT1A1 alleles (7-TA and 8-TA) were associated with modestly increased HPRT mutation frequency (p<0.05) while the same low expression genotypes were not significantly associated with micronuclei frequencies (K-positive or K-negative) when compared to high expression genotypes (5-TA and 6-TA). We found weak evidence that UGT1A1 genotypes containing 7-TA and 8-TA were associated with increased GPA{_}N0 mutant frequency relative to 5/5, 5/6, 6/6 genotypes (p<0.05). These data suggest that UGT1A1 genotype may modulate somatic mutation of some types, in some cell lineages, by a mechanism not involving bilirubin antioxidant activity. More detailed studies examining UGT1A1 promoter variation, oxidant/antioxidant balance and

  11. 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

  12. 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

  13. Vascular cognitive impairment

    OpenAIRE

    Rebecca F. Gottesman; Hillis, Argye E.

    2014-01-01

    The term vascular cognitive impairment (VCI) has been proposed to encompass all people with cognitive impairment of cerebrovascular origin. VCI is not a single condition, but has several clinical presentations, etiologies, and treatment. VCI forms a spectrum that includes vascular dementia, mixed Alzheimer’s disease with a vascular component, and VCI that does not meet dementia criteria. Multiple pathophysiological mechanisms contribute to VCI, accounting for its heterogeneity. Although main ...

  14. 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.

  15. 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], p<0.05). The anti-proliferative effects of S. platensis were also shown in vivo, where inhibition of pancreatic cancer growth was evidenced since the third day of treatment (p < 0.05). All tested compounds decreased generation of mitochondrial ROS and glutathione redox status (p = 0.0006; 0.016; and 0.006 for S. platensis, PCB, and chlorophyllin, respectively). In conclusion, S. platensis and its tetrapyrrolic components substantially decreased the proliferation of experimental pancreatic cancer. These data support a chemopreventive role of this edible alga. Furthermore, it seems that dietary supplementation with this alga might enhance systemic pool of tetrapyrroles, known to be higher in subjects with Gilbert syndrome. PMID:24552870

  16. Cerebral palsy associated with bilirubin-encephalopathy and its precipitating factors%胆红素脑病引起的脑性瘫痪及其促发因素分析

    Institute of Scientific and Technical Information of China (English)

    侯梅; 王海桥; 孙殿荣; 王珂; 赵建慧

    2009-01-01

    each patient, including physical examination, auditory brainstem respose(ABR) , brain CT/MRI , and Gesell development scales. Results All the 35 cases (female 10, male 25, ranging from six months to nine years and two months) showed involuntary motor pattern associated with dyskinestic cerebral palsy, 16 cases with dental dysplasia, six accompanied by bilateral hearing impairment and their hearing threshold measured by ABR from 75 dB to 105dB, one with West syndrome. Among the 35 children, 22 cases were admitted due to "kernicterus" and "bilirubin-encephalopathy" during neonatal period with etiological diagnosis mainly as ABO hemocytolysis or infection. Intervention time of hyperbilirubinemia was from 2 days to 1 month (the median seven days)after birth with TSB ranging from 400~ 889.9 μmol/L(the median 580 μmol/L). Ten cases had accepted exchange transfusion, the others accepted phototherapy, albumin infusion and Yin-zhi-huang peros. The other 14 cases hadn't seen doctors or been treated during neonatal period. Conclusion Our series indicate that the parents and elementary medical staff are still not aware enough of the importance of neonatal jaundice, which results in the delayed diagnosis and treatment of hyperbilirubi-naemia.How to do a good job in primary and secondary prevention of bilirubin-encephalopathy and to avoid the occur- rence of related cerebral palsy is a critical problem we should solve.

  17. Vascular cognitive impairment

    Directory of Open Access Journals (Sweden)

    N.V. Vakhnina

    2014-01-01

    Full Text Available Vascular pathology of the brain is the second most common cause of cognitive impairment after Alzheimer's disease. The article describes the modern concepts of etiology, pathogenetic mechanisms, clinical features and approaches to diagnosis and therapy of vascular cognitive impairment (VCI. Cerebrovascular accident, chronic cerebral circulatory insufficiency and their combination, sometimes in combination with a concomitant neurodegenerative process, are shown to be the major types of brain lesions leading to VCI. The clinical presentation of VCI is characterized by the neuropsychological status dominated by impairment of the executive frontal functions (planning, control, attention in combination with focal neurological symptoms. The diagnosis is based on comparing of the revealed neuropsychological and neurological features with neuroimaging data. Neurometabolic, acetylcholinergic, glutamatergic, and other vasoactive drugs and non-pharmacological methods are widely used to treat VCI. 

  18. 血清胆红素与老年冠心病的相关性探讨%Correlation study of serum bilirubin and coronary heart disease in elderly patients

    Institute of Scientific and Technical Information of China (English)

    颜承靖; 颜群

    2013-01-01

    目的 探讨血清胆红素与老年冠心病的相关性. 方法 选取本院冠心病患者37例和体检健康老年者54例.记录所有研究对象基本资料,检测血清胆红素、血脂、肝功能,并进行相关分析.结果 冠心病组的血清总胆红素(TBIL)和间接胆红素(IBIL)浓度显著低于非冠心病组(P<0.05),而直接胆红素(DBIL)的水平在2组之间无统计学差异. 结论 在老年冠心病患者中血清胆红素(TBIL、IBIL)水平降低,在生理范围内轻度升高的胆红素是冠心痛的一个保护因素.%Objective To investigate the relationship between serum bilirubin and coronary heart disease in elderly patients. Methods Thirty-seven patients with coronary heart disease and 54 healthy cases were enrolled in this study. The clinical data of all the subjects were recorded. The levels of serum bilirubin,blood lipid,liver function were analyzed. Results The levels of serum total bilirubin (TBIL) and indirect bilirubin (IBIL) in the patients with coronary heart disease were significantly lower than those in the healthy cases (P <0. 05). The level of direct bilirubin ( DBIL) showed no difference between the two groups. Conclusions The level of serum bilirubin are decreased in elderly patients with coronary artery disease. In the physiological range mildly elevated bilirubin is one of the protective factors to coronary heart disease.

  19. Endocrine disruptors and childhood social impairment.

    Science.gov (United States)

    Miodovnik, Amir; Engel, Stephanie M; Zhu, Chenbo; Ye, Xiaoyun; Soorya, Latha V; Silva, Manori J; Calafat, Antonia M; Wolff, Mary S

    2011-03-01

    Prenatal exposure to endocrine disruptors has the potential to impact early brain development. Neurodevelopmental toxicity in utero may manifest as psychosocial deficits later in childhood. This study investigates prenatal exposure to two ubiquitous endocrine disruptors, the phthalate esters and bisphenol A (BPA), and social behavior in a sample of adolescent inner-city children. Third trimester urines of women enrolled in the Mount Sinai Children's Environmental Health Study between 1998 and 2002 (n=404) were analyzed for phthalate metabolites and BPA. Mother-child pairs were asked to return for a follow-up assessment when the child was between the ages of 7 and 9 years. At this visit, mothers completed the Social Responsiveness Scale (SRS) (n=137), a quantitative scale for measuring the severity of social impairment related to Autistic Spectrum Disorders (ASD) in the general population. In adjusted general linear models increasing log-transformed low molecular weight (LMW) phthalate metabolite concentrations were associated with greater social deficits (β=1.53, 95% CI 0.25-2.8). Among the subscales, LMWP were also associated with poorer Social Cognition (β=1.40, 95% CI 0.1-2.7); Social Communication (β=1.86, 95% CI 0.5-3.2); and Social Awareness (β=1.25, 95% CI 0.1-2.4), but not for Autistic Mannerisms or Social Motivation. No significant association with BPA was found (β=1.18, 95% CI -0.75, 3.11). Prenatal phthalate exposure was associated with childhood social impairment in a multiethnic urban population. Even mild degrees of impaired social functioning in otherwise healthy individuals can have very important adverse effects over a child's lifetime. These results extend our previous finding of atypical neonatal and early childhood behaviors in relation to prenatal phthalate exposure. PMID:21182865

  20. 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

  1. Specific Language Impairment

    Science.gov (United States)

    ... to distinguish between children who are struggling to learn a new language and children with true language impairments. After studying a large group of Hispanic children who speak English as a second language, NIDCD-funded researchers have developed a dual ...

  2. Visual Impairment, Including Blindness

    Science.gov (United States)

    ... top Adapting the Environment Making adaptations to the environment where a child with a visual impairment lives, works, or plays ... can consult, depending on your role in the child’s life, are: Family Connect ... to the Physical Environment: Setting up a Classroom for Students with Visual ...

  3. 高血压患者血清胆红素与脉搏波速度相关性研究%Relationship between Serum Bilirubin and Pulse Wave Velocity in Hypertensive Patients

    Institute of Scientific and Technical Information of China (English)

    黎兰芳

    2013-01-01

    目的 探讨高血压患者血清胆红素与脉搏波速度的关系.方法 应用康普乐全自动动脉硬化检测系统检测508例确诊为原发性高血压患者的颈-股动脉脉搏波速度(CF-PWV),并检测空腹血清总胆红素.将总胆红素>11 μmol·L-1者作为高胆红素组(n= 221),总胆红素≤11μmol·L-1者作为低胆红素组(n=287),对血清总胆红素与CF-PWV值进行相关性分析.结果 高胆红素组CF-PWV值为(9.04士1.20)m·s-1低于低胆红素组的(10.89±2.18)m·s-1,2组比较差异有统计学意义(P<0.01);血清总胆红素与CF-PWV值呈负相关(r=-0.636,P<0.01).结论 高血压患者血清总胆红素与脉搏波速度呈负相关.%Objective To study the relationship between serum bilirubin and pulse wave velocity (PWV) in hypertensive patients.Methods Carotid-femoral PWV(CF-PWV) was determined by using Complior SP automatic arteriosclerosis measurement system in 508 patients with essential hypertension.According to the fasting serum total bilirubin levels,patients were divided into high bilirubin group (>11 μmol · L-1,n=221) and low bilirubin group (≤11 μmol · L-1,n=287).The correlation between serum total bilirubin and CF-PWV was analyzed.Results Compared with low bilirubin group,CF-PWV significantly decreased in high bilirubin group [(9.04±1.20)m · s-1 vs (10.89±2.18)m · s-1,P<0.01].There was a negative correlation between serum total bilirubin levels and CF-PWV (r=-0.636,P<0.01).Conclusion Serum total bilirubin levels are negatively correlated with PWV in hypertensive patients.

  4. Principles of a competitive binding assay for the study of the interactions of poorly water-soluble ligands with their soluble binding partners. Application to bilirubin with the use of Sephadex G-10 as a competitive adsorbent.

    Science.gov (United States)

    Meuwissen, J A; Kinnaert, M; Michiels, G; Heirwegh, K P

    1988-01-01

    1. A generally applicable method is described for obtaining experimental data on the interactions between a poorly water-soluble ligand and soluble binding factors, with the use of chemically inert solid adsorbent. The equilibrium distribution of the ligand between the liquid phase containing the soluble binders and the adsorbent must be measured and knowledge of the binding isotherm of the adsorbent is required. Procedures are given for the calculation of the binding parameters. 2. The method has been applied to quantify the interactions of bilirubin with serum and liver cytosol from the rat, Sephadex G-10 serving as the competing adsorbent. Reversible adsorption keeps the concentration of the free ligand low, thereby preventing formation of colloidal bilirubin. The sensitivity of the procedure accommodates the rather high binding affinities by which bilirubin generally interacts with its specific binding proteins. 3. The binding activities of serum and liver cytosol are of comparable magnitude. Binding of bilirubin by rat serum can be described by two independent binding sites, the affinities of which differ by two orders of magnitude. Only the site with the higher affinity appears to be of physiological importance. The major bilirubin-binding sites of rat liver cytosol seem to contribute equally to the overall binding activity of this preparation, provided that GSH is present. PMID:2449176

  5. Impaired inhibitory control in recreational cocaine users.

    Directory of Open Access Journals (Sweden)

    Lorenza S Colzato

    Full Text Available Chronic use of cocaine is associated with impairment in response inhibition but it is an open question whether and to which degree findings from chronic users generalize to the upcoming type of recreational users. This study compared the ability to inhibit and execute behavioral responses in adult recreational users and in a cocaine-free-matched sample controlled for age, race, gender distribution, level of intelligence, and alcohol consumption. Response inhibition and response execution were measured by a stop-signal paradigm. Results show that users and non users are comparable in terms of response execution but users need significantly more time to inhibit responses to stop-signals than non users. Interestingly, the magnitude of the inhibitory deficit was positively correlated with the individuals lifetime cocaine exposure suggesting that the magnitude of the impairment is proportional to the degree of cocaine consumed.

  6. Evaluation of new oxidation methods for the measurement of bilirubin on the aeroset clinical chemistry analyzer and comparison with methods on the Hitachi 717.

    Science.gov (United States)

    Sturm, Ernhard; Albrecht-Groos, Ragnhild; Seyfarth, Michael

    2002-01-01

    We evaluated analytical and performance quality of the new oxidation methods for direct and total bilirubin on the Abbott Aeroset clinical chemistry analyzer. Within-day imprecisions for Abbott Aeroset assays ranged from 0.7 to 2.9% and between-day imprecisions from 2.1 to 7.3%. Inaccuracies as compared with the control "target values" for the Jendrassik-Gróf method showed deviations of -18.2 to +4.2%. Limits of detection were determined and showed very low values of 300 micromol/l. A method comparison for 100 patient samples with established Jendrassik-Gróf and DPD methods on the Roche Hitachi 717 showed good linearities between the investigated methods (r > or = 0.995). Due to slopes that ranged from 0.829 to 0.950, reference ranges for the oxidation methods differ slightly from those of established Roche Jendrassik-Gróf methods, but results can be adapted by the introduction of converting factors. In conclusion, the oxidation bilirubin assays revealed convincing analytical and performance qualities for medical needs that were similar or even better than for established methods. Application of the oxidation methods on the Aeroset clinical chemistry analyzer also improves laboratory efficiency by increasing throughput, speed of obtaining results and lowered sample and reagent volumes compared to established methods.

  7. Study on the risk factors and preventive measures of neonatal bilirubin encephalopathy%新生儿胆红素脑病危险因素与预防措施研究

    Institute of Scientific and Technical Information of China (English)

    吴俊超; 刘军民; 刘华勇

    2011-01-01

    目的:探讨导致新生儿胆红索脑病的危险因索,优化其关键性预防措施.方法:回顾性分析1998年1月~2007年12月4 683例新生儿高间接胆红素血症(HB)及其中64例并发胆红素脑病(BE)的临床资料.结果:①4 683例HB患儿中的甲组2 366例为该院分娩,接受胆红素动态监测,HB得到及时治疗,无BE发生;乙组2 317例为市、县、乡镇分娩,没有动态监测胆红素并及时治疗HB,并发64例BE.甲乙两组病因分布对比,差异无统计学意义(P>0.05);②乙组2 317例中,1 187例接受过围产期保健服务者,并发16例BE,1 130例未接受服务者,并发48例BE,对比检验,差异有统计学意义(P<0.01);③导致64例BE的危险因素为:一是围产期母儿因素、溶血因素,感染因素等多病因并存,二是存在缺氧、酸中毒、低体温、低蛋白、低血糖、低热量等合并症.结论:建立健全对HB发生、发展的动态监测机制,针对病因,及早治疗HB,防治合并症,是预防或消除BE的关键措施;加强围产期保键服务,也能有效地降低BE发生率.%Objective: To explore the risk factors of neonatal bilirubin encephalopathy, and optimize its key preventive measures. Methods: The clinical data of 4 683 neonates with indirect hyperbilirubinemia and 64 neonates with indirect hyperbilirubinemia combined with bilirubin encephalopathy from January 1998 to December 2007 were analyzed retrospectively. Results: Among 4 683 neonates with indirect hyperbilirubinemia, 2 366 neonates in group A deliveried in the hospital received dynamic monitoring of bilirubin and they were treated timely, no bilirubin encephalopathy occurred; 2 317 neonates in group B deliveried in hospitals in other cities, counties and townships didn't receive dynamic monitoring of bilirubin and they were not treated timely, 64 neonates combined with bilirubin encephalopathy. There was no significant difference in the distribution of etiological causes between the two groups

  8. Clinical application value of bilirubin detection in cerebrospinal fluid of neonates with hyperbilirubinemia%高胆红素血症新生儿脑脊液胆红素检测的临床应用价值探讨

    Institute of Scientific and Technical Information of China (English)

    周柏林; 王全震; 吕清秀; 董静

    2013-01-01

    Objective:To explore the clinical application value of unconjugated bilirubin detection in cerebrospinal fluid of neonates with hyperbilirubinemia.Methods:The levels of unconjugated bilirubin in cerebrospinal fluid and blood of 285 neonates with hyperbilirubinemia were detected,the ratio of unconjugated bilirubin to albumin (B/A) was calculated,and neonatal behavioral neurological assessment (NBNA) was performed.Results:The levels of unconjugated bilirubin in blood and cerebrospinal fluid,B/A in blood in neonates with bilirubin encephalopathy at warning period and spasm period were statistically significantly higher than those in neonates with simple hyperbilirubinemia (P < 0.05),the level of unconjugated bilirubin in cerebrospinal fluid of neonates with bilirubin encephalopathy at spasm period was statistically significantly higher than that of neonates with bilirubin encephalopathy at warning period (P < 0.05),the levels of unconjugated bilirubin in blood and cerebrospinal fluid,B/A in cerebrospinal fluid of neonates with abnormal NBNA score were statistically significantly higher than those of neonates with normal NBNA score,there was a significant correlation between unconjugated bilirubin and NBNA score in cerebrospinal fluid.Conclusion:Unconjugated bilirubin detection in cerebrospinal fluid not only diagnose bilirubin encephalopathy early,but also reflect the brain function of neonates with hyperbilirubinemia.%目的:探讨脑脊液中未结合胆红素检测在高胆红素血症新生儿中的临床应用价值.方法:对285例高胆红素血症新生儿的脑脊液和血液未结合胆红素水平进行检测,计算未结合胆红素/白蛋白比值(B/A),并进行新生儿行为神经评分(NBNA).结果:警告期和痉挛期的胆红素脑病新生儿血中未结合胆红素(UCB)、脑脊液(CSF)中UCB和血B/A比值均明显高于单纯高胆红素血症的新生儿,差异有统计学意义(P<0.05),并且出现痉挛期的新生儿CSF中UCB高于警

  9. Night time aircraft noise exposure and children′s cognitive performance

    OpenAIRE

    Stephen Stansfeld; Staffan Hygge; Charlotte Clark; Tamuno Alfred

    2010-01-01

    Chronic aircraft noise exposure in children is associated with impairment of reading and long-term memory. Most studies have not differentiated between day or nighttime noise exposure. It has been hypothesized that sleep disturbance might mediate the association of aircraft noise exposure and cognitive impairment in children. This study involves secondary analysis of data from the Munich Study and the UK Road Traffic and Aircraft Noise Exposure and Children′s Cognition and Health (RANCH) Stud...

  10. Cryotherapy impairs proprioception function?

    OpenAIRE

    Cordeiro, Nuno; Henriques, Sara

    2014-01-01

    INTRODUCTION: Cryotherapy application over a joint causes a nerve conduction velocity decrease and proprioceptive changes. OBJECTIVE: This study aims to determine if cryotherapy impairs proprioception acuity. METHODS: Proprioception was assessed by joint position sense (JPS), measured with an isokinetic dynamometer Biodex System 3, in twenty one females on experimental group, before 15 minutes cryotherapy (T0) and immediately after (T1). A control group (n=20) performed also the JPS...

  11. Neurological Impairment: Nomenclature and Consequences.

    Science.gov (United States)

    Spears, Catherine E.; Weber, Robert E.

    Neurological impairment as discussed includes a range of disabilities referred to as neurological impairment: minimal brain dysfunction/damage, developmental disability, perceptual handicap, learning disability, hyperkinetic behavioral syndrome, and others. Defined are causes of neurological impairment and methods of diagnosis. Symptoms…

  12. Impairment, disability, and handicap.

    Science.gov (United States)

    Mooney, V

    1987-08-01

    It seems clear that the orthopedic surgeon cannot separate impairment from disability. The measurement of impairment is clouded by the inability to measure dynamic function. A range of motion demonstrated by a patient in the doctor's office does not fully describe the functional potential of either the extremity or the spine. Moreover, the rules by which disability is defined are interpreted with a natural sympathy of the physician's care for the patient. The physician may have less sympathy if the individual being reviewed is a client of an insurance company or of an attorney, compared to being a "private" patient. In the future, the orthopedic surgeon would focus on the musculoskeletal handicap rather than disability, or function rather than impairment. Function must be measured in a dynamic manner. The guidelines for definition of function or dysfunction should be similar to those used in sports medicine regarding the decision as to when the athlete can resume sports. What was the capacity before injury? How close to the normal capacity has medical care restored function? This includes measurements of passage of time and consideration of the desire to return to previous activity. The goal is the development of methods that will accurately measure dynamic musculoskeletal function. Visceral organ systems have biochemical standards of measurement; comparable standards must be devised for the musculoskeletal system. PMID:2955986

  13. Study of relationship between the levels of serum bilirubin ,uric acid and unstable angina pectoris%不稳定型心绞痛患者血清胆红素及尿酸水平的分析

    Institute of Scientific and Technical Information of China (English)

    梁启权; 曾胜宏

    2009-01-01

    目的 探讨冠心病不稳定型心绞痛与胆红素及尿酸的关系.方法 将入选202例冠心病不稳定型心绞痛患者,采集空腹静脉血测定总胆红素、直接胆红素、间接胆红素及尿酸,比较其心绞痛发作时、3个月、6个月及1年内未再发作时胆红素及尿酸的变化情况.结果 心绞痛发作时胆红素降低,尿酸偏高.结论 胆红素和尿酸水平可间接反映不稳定型心绞痛机体氧化、抗氧化情况,胆红素对评估病情有一定帮助.%Objective To investigate the relationship between the levels of serum bilirubin,uric acid(UA) and coronary heart disease unstable angina pectoris.Methods The leves of total bilirubin (TBIL),direct bilirubin (DBIL),indirect bilirubin(IBIL) and UA in venous blood by limosis were determind in 202 patients with unstable angina pectoris.We determine the different levels of TBIL,DBIL,IBIL and UA when they were suffering from angina pectoris.Then we respectively determine the levels of TBIL,DBIL,IBIL and UA in 3 months,6 months and 12 months after they had been suffered from angina pectoris.Results The levels of serum bilirubin were lower and UA were higher,when the patients were suffering from angina pectoris.Conclusion We can indirectly assess the oxidative and antioxidative activities by testing bilirubin and UA in unstable angina pectoris.

  14. Maternal nicotine exposure leads to higher liver oxidative stress and steatosis in adult rat offspring.

    Science.gov (United States)

    Conceição, E P; Peixoto-Silva, N; Pinheiro, C R; Oliveira, E; Moura, E G; Lisboa, P C

    2015-04-01

    Early nicotine exposure causes future obesity and insulin resistance. We evaluated the long-term effect of the maternal nicotine exposure during lactation in liver oxidative status, insulin sensitivity and morphology in adult offspring. Two days after birth, osmotic minipumps were implanted in the dams: nicotine (N), 6 mg/kg/day for 14 days or saline (C). Offspring were killed at 180 days. Protein content of superoxide dismutase, glutathione peroxidase, catalase, nitrotyrosine, 4HNE, IRS1, Akt1 and PPARs were measured. MDA, bound protein carbonyl content, SOD, GPx and catalase activities were determined in liver and plasma. Hepatic morphology and triglycerides content were evaluated. Albumin and bilirubin were determined. In plasma, N offspring had higher catalase activity, and SOD/GPx ratio, albumin and bilirubin levels but lower MDA content. In liver, they presented higher MDA and 4HNE levels, bound protein carbonyl content, SOD activity but lower GPx activity. N offspring presented an increase of lipid droplet, higher triglyceride content and a trend to lower PPARα in liver despite unchanged insulin signaling pathway. Early nicotine exposure causes oxidative stress in liver at adulthood, while protect against oxidative stress at plasma level. In addition, N offspring develop liver microsteatosis, which is related to oxidative stress but not to insulin resistance. PMID:25662863

  15. 急性脑梗死后胆红素升高与卒中严重性的相关研究%Research on Bilirubin increased after AIS associated with the severity of stroke

    Institute of Scientific and Technical Information of China (English)

    张俊玲

    2015-01-01

    Objectives To observe the changes of bilirubin in earlier acute ischemic stroke ( AIS) and whether such changes are associated with the severity of the stroke.Methods Bilirubin and other biochemical indexes were measured in 108 AIS patients and 38 transientischemic attack ( TIA) patients which set as the control group.First, the level of bilirubin and it’s distribution were com-pared between the AIS and control group.According to a cut-off point, we next analyzed the impacted factors of elevated bilirubin in-cluding the direct bilirubin (Dbil) and total bilirubin(Tbil), especially the correlation between elevated bilirubin and the severity of stroke.Results The serum direct bilirubin and total bilirubin in patients with AIS group was significantly higher than the TIA group.In both groups, we found the distribution of intervals is different.The percentage of low bilirubin is lower in AIS group com-pared with TIA group,while the percentage of high bilirubin is higher in AIS group compared with TIA group.Conclusions The ser-um levels of Dbil and Tbil were increased after AIS, which linked to the severity of stroke.%目的:观察急性脑梗死( acute ischemic stroke,AIS)早期胆红素的变化情况及此种改变是否与卒中的严重程度相关。方法选取108例AIS患者作为试验组,38例TIA患者作为对照组,测定所有患者的胆红素以及其他相关的生化指标。首先,比较AIS组与对照组胆红素的水平以及其分布。根据设立的节点,我们分析了胆红素(包括直接胆红素以及总胆红素)升高的影响因素,尤其是分析升高的胆红素与卒中严重程度之间的相关性。结果 AIS组患者血清直接胆红素以及总胆红素显著高于TIA组。在两组中我们发现其分布区间也不同,AIS的低胆红素组比率低于TIA组,而AIS组高胆红素的百分比相比TIA组较高。结论血清直接胆红素和总胆红素水平在脑卒中后升高,并与卒中的严重程度相关。

  16. 糖尿病肾病患者胆红素和血红蛋白的相关性及临床意义%Patients with Diabetic Nephropathy and its Clinical Significance of Bilirubin and Hemoglobin

    Institute of Scientific and Technical Information of China (English)

    尤守堂; 沈红艳

    2015-01-01

    Objective To analyze the relationship between the diabetic nephropathy patients peripheral blood bilirubin and hemoglobin, to explore the factors inlfuencing the serum bilirubin in patients with nephropathy of diabetes. Methods This study included 106 patients with diabetic nephropathy patients, 113 cases of diabetic patients without complications and 120 healthy controls were detected in the peripheral blood, the total bilirubin, direct bilirubin, indirect bilirubin and hemoglobin content and total bilirubin and hemoglobin correlation analysis. Results Compared with the control group and diabetic group without complications, diabetic nephropathy group total bilirubin, direct bilirubin, indirect bilirubin and hemoglobin levels were signiifcantly reduced, the differences were statistically signiifcant (P<0.001);correlation analysis showed, diabetic nephropathy group total bilirubin level was positively associated with hemoglobin (r=0.455, P<0.001). Conclusion Decreased serum bilirubin in patients with diabetic nephropathy associated with the lower hemoglobin, positive correction has an important role for the treatment of anemia in patients with diabetic nephropathy.%目的:分析糖尿病肾病患者外周血胆红素水平与血红蛋白之间的关系,探讨糖尿病肾病患者血清胆红素变化的影响因素。方法研究对象包括106例糖尿病肾病患者,113例糖尿病无并发症患者和120例健康对照者,检测上述各组外周血总胆红素、直接胆红素、间接胆红素和血红蛋白含量并分析总胆红素与血红蛋白相关性。结果与对照组和糖尿病无并发症组比较,糖尿病肾病组总胆红素、直接胆红素、间接胆红素及血红蛋白水平均显著降低,差异均有统计学意义(P<0.001);相关分析显示,糖尿病肾病组总胆红素水平与血红蛋白呈正相关(r=0.455,P<0.001)。结论糖尿病肾病患者血清胆红素的降低与血红蛋白降低有关,积

  17. Correlations between periparturient serum concentrations of non-esterified fatty acids, beta-hydroxybutyric acid, bilirubin, and urea and the occurrence of clinical and subclinical postpartum bovine endometritis

    Directory of Open Access Journals (Sweden)

    Tenhagen Bernd-Alois

    2010-10-01

    Full Text Available Abstract Background Postpartum endometritis in cattle is a multifactorial disease with high economic impact. Both, clinical endometritis (CE and subclinical endometritis (SCE result in decreased reproductive performance. Results from in vitro studies led to the implication that non-esterified fatty acids (NEFA, beta-hydroxybutyric acid (BHBA, bilirubin, and urea could be used as predictors for endometritis in veterinary practice. In this field study, we set out to establish optimal predictor cut points of these metabolic parameters for the detection of CE and SCE. Serum samples were collected one week prior to parturition (wk -1, in the first week postpartum (wk +1 and between 28 and 35 days postpartum (wk +5 from 209 Holstein-Friesian cows. At wk +5, all cows were examined for signs of CE and SCE. Results Higher concentrations of urea at wk +1 were associated with increased odds of CE (OR = 1.7, P = 0.04 in primiparous (PP cows. A predictor cut point of 3.9 mmol/L (sensitivity: 61%, specificity: 70% was determined. In multiparous (MP cows, the logistic regression model revealed that higher concentrations of NEFA at wk -1 were associated with increased odds of CE and SCE (healthy vs. CE: OR = 9.1, P = 0.05; healthy vs. SCE: OR = 12.1, P = 0.04. A predictor cut point of 0.3 mmol/L (sensitivity: 38%, specificity: 87% and sensitivity: 35%, specificity: 89%, respectively was determined. Increasing concentrations of urea at wk +5 were associated with decreased odds of CE (healthy vs. CE: OR = 0.6, P = 0.01; SCE vs. CE: OR = 0.5, P = 0.03. A predictor cut point of 3.8 mmol/L (sensitivity: 52%, specificity: 81% was determined. For BHBA and bilirubin relationships with CE or SCE were not detected. Conclusions The corresponding combinations of sensitivity and specificity of the determined predictor cut points were not satisfactory for practical use. Thus, the analysed parameters, i.e. NEFA, BHBA, bilirubin, and urea, at the chosen time points, i.e. at wk

  18. Correlations between periparturient serum concentrations of non-esterified fatty acids, beta-hydroxybutyric acid, bilirubin, and urea and the occurrence of clinical and subclinical postpartum bovine endometritis

    Science.gov (United States)

    2010-01-01

    Background Postpartum endometritis in cattle is a multifactorial disease with high economic impact. Both, clinical endometritis (CE) and subclinical endometritis (SCE) result in decreased reproductive performance. Results from in vitro studies led to the implication that non-esterified fatty acids (NEFA), beta-hydroxybutyric acid (BHBA), bilirubin, and urea could be used as predictors for endometritis in veterinary practice. In this field study, we set out to establish optimal predictor cut points of these metabolic parameters for the detection of CE and SCE. Serum samples were collected one week prior to parturition (wk -1), in the first week postpartum (wk +1) and between 28 and 35 days postpartum (wk +5) from 209 Holstein-Friesian cows. At wk +5, all cows were examined for signs of CE and SCE. Results Higher concentrations of urea at wk +1 were associated with increased odds of CE (OR = 1.7, P = 0.04) in primiparous (PP) cows. A predictor cut point of 3.9 mmol/L (sensitivity: 61%, specificity: 70%) was determined. In multiparous (MP) cows, the logistic regression model revealed that higher concentrations of NEFA at wk -1 were associated with increased odds of CE and SCE (healthy vs. CE: OR = 9.1, P = 0.05; healthy vs. SCE: OR = 12.1, P = 0.04). A predictor cut point of 0.3 mmol/L (sensitivity: 38%, specificity: 87% and sensitivity: 35%, specificity: 89%, respectively) was determined. Increasing concentrations of urea at wk +5 were associated with decreased odds of CE (healthy vs. CE: OR = 0.6, P = 0.01; SCE vs. CE: OR = 0.5, P = 0.03). A predictor cut point of 3.8 mmol/L (sensitivity: 52%, specificity: 81%) was determined. For BHBA and bilirubin relationships with CE or SCE were not detected. Conclusions The corresponding combinations of sensitivity and specificity of the determined predictor cut points were not satisfactory for practical use. Thus, the analysed parameters, i.e. NEFA, BHBA, bilirubin, and urea, at the chosen time points, i.e. at wk -1, at wk +1

  19. The visually impaired child.

    Science.gov (United States)

    Thompson, Lisa; Kaufman, Lawrence M

    2003-02-01

    This article discusses the causes of childhood blindness and how the primary care provider may begin the appropriate steps toward diagnosing and managing the visually impaired child. Community resources (see Box 3) and low-vision programs in schools should be used so that parents do not need to reinvent strategies to raise a blind child. Worldwide, childhood blindness, which places is a tremendous burden on families and communities of the third world, is mostly preventable with improved hygiene, diet, and immunization. PMID:12713115

  20. Specific language impairment.

    Science.gov (United States)

    Kamhi, Alan G; Clark, Mary Kristen

    2013-01-01

    The acquisition of language is one of the most important achievements in young children, in part because most children appear to acquire language with little effort. Some children are not so fortunate, however. There is a large group of children who also have difficulty learning language, but do not have obvious neurological, cognitive, sensory, emotional, or environmental deficits. Clinicians often refer to these children as language disordered or language impaired. Researchers tend to refer to these children as specific language impaired (SLI). Children with SLI have intrigued researchers for many years because there is no obvious reason for their language learning difficulties. SLI has been found to be an enduring condition that begins in early childhood and often persists into adolescence and adulthood. The language problems of children with SLI are not limited to spoken language; they also affect reading and writing and thus much of academic learning. Knowledge of the characteristics of SLI should aid physicians, pediatricians, and early childhood specialists to identify these children during the preschool years and ensure that they receive appropriate services. With high-quality language intervention and literacy instruction, most children with SLI should be able to perform and function adequately in school and beyond. PMID:23622167

  1. Fertility impairment in radiotherapy.

    Science.gov (United States)

    Biedka, Marta; Kuźba-Kryszak, Tamara; Nowikiewicz, Tomasz; Żyromska, Agnieszka

    2016-01-01

    Infertility as a result of antineoplastic therapy is becoming a very important issue due to the growing incidence of neoplastic diseases. Routinely applied antineoplastic treatments and the illness itself lead to fertility disorders. Therapeutic methods used in antineoplastic treatment may cause fertility impairment or sterilization due to permanent damage to reproductive cells. The risk of sterilization depends on the patient's sex, age during therapy, type of neoplasm, radiation dose and treatment area. It is known that chemotherapy and radiotherapy can lead to fertility impairment and the combination of these two gives an additive effect. The aim of this article is to raise the issue of infertility in these patients. It is of growing importance due to the increase in the number of children and young adults who underwent radiotherapy in the past. The progress in antineoplastic therapy improves treatment results, but at the same time requires a deeper look at existential needs of the patient. Reproductive function is an integral element of self-esteem and should be taken into account during therapy planning. PMID:27647982

  2. Bilirubin nomograms for identification of neonatal hyperbilirubinemia in healthy term and late-preterm infants:a systematic review and meta-analysis

    Institute of Scientific and Technical Information of China (English)

    Zhang-Bin Yu; Shu-Ping Han; Chao Chen

    2014-01-01

    Background: Hyperbilirubinemia occurs in most healthy term and late-preterm infants, and must be monitored to identify those who might develop severe hyperbilirubinemia. Total serum bilirubin (TSB) or transcutaneous bilirubin (TcB) nomograms have been developed and validated to identify neonatal hyperbilirubinemia. This study aimed to review previously published studies and compare the TcB nomograms with the TSB nomogram, and to determine if the former has the same predictive value for signifi cant hyperbilirubinemia as TSB nomogram does. Methods: A predefined search strategy and inclusion criteria were set up. We selected studies assessing the predictive ability of TSB/TcB nomograms to identify significant hyperbilirubinemia in healthy term and latepreterm infants. Two independent reviewers assessed the quality and extracted the data from the included studies. Meta-Disc 1.4 analysis software was used to calculate the pooled sensitivity, specificity, and positive likelihood ratio of TcB/TSB nomograms. A pooled summary of the receiver operating characteristic of the TcB/TSB nomograms was created. Results: After screening 187 publications from electronic database searches and reference lists of eligible articles, we included 14 studies in the systematic review and meta-analysis. Eleven studies were of medium methodological quality. The remaining three studies were of low methodological quality. Seven studies evaluated the TcB nomograms, and seven studies assessed TSB nomograms. There were no differences between the predictive abilities of the TSB and TcB nomograms (the pooled area under curve was 0.819 vs. 0.817). Conclusions: This study showed that TcB nomograms had the same predictive value as TSB nomograms, both of which could be used to identify subsequent signifi cant hyperbilirubinemia. But this result should be interpreted cautiously because some methodological limitations of these included studies were identifi ed in this review.

  3. 血清胆红素与尿酸检验对冠心病的诊断价值分析%Diagnostic Value of Serum Bilirubin and Uric Acid in Patients with Coronary Heart Disease

    Institute of Scientific and Technical Information of China (English)

    黄飞

    2016-01-01

    Objective To investigate the role of serum bilirubin and uric acid in the detection of coronary artery disease.Methods Biochemical analysis of 82 cases of various indicators of coronary heart disease patients and healthy people for comparison.Results Bilirubin in observation group was significantly lower than healthy people;higher serum uric acid levels ( <0.05),different groups of serum bilirubin and uric acid levels in patients with coronary heart disease were significantly different ( <0.05).Conclusion Serum bilirubin and uric acid levels in patients with coronary heart disease is detected may be clinically assess the extent of reference.%目的:探讨血清胆红素与尿酸检测对冠心病的作用。方法82例冠心病患者与健康人员对比各生化指标分析。结果观察组胆红素明显低于健康体检者。血清尿酸水平较高(<0.05)﹐不同组别冠心病患者血清胆红素与尿酸水平差异显著(<0.05)。结论冠心病患者血清胆红素与尿酸水平检测可为临床评估病症程度参考。

  4. 2型糖尿病患者血清胆红素水平与糖尿病病程负相关%Increased duration of diabetes is associated with lower serum bilirubin concentration in type 2 diabetic patients

    Institute of Scientific and Technical Information of China (English)

    李佳霖; 陈艳曙; 徐淼; 褚建平; 励丽

    2016-01-01

    Objective To investigate the association between physiological serum bilirubin concentration and duration of type 2 diabetes. Methods A total of 1 272 patients with type 2 diabetes admitted to the Department of Endocrinology of Ningbo First Hospital from January 2013 to June 2015 were included for the study. Clinic parameters were collected from electronic medical records. All subjects were classified into four groups by diabetes duration quartiles (<5 years, 5-9 years, 10-14 years and≥15 years). The adjusted concentration of three types of bilirubin were calculated and compared using covariance analysis. Pearson correlation analysis and multiple linear regression analysis were adopted to examine the relationship between duration of diabetes and serum bilirubin. Results With increase of diabetes duration from the lowest quartiles to the highest quartiles, serum total bilirubin, direct bilirubin and indirect bilirubin concentration tended to decrease. This trend persisted after adjustment for age, gender, hemoglobin, smoking, drinking, blood pressure, lipid profile, weight, ALT, AST, HbA1c and statin use. The adjusted mean concentration of total bilirubin from the lowest quartiles to the highest quartiles for diabetes duration was 13.26, 12.36, 12.07 and 11.71mmol/L (F=4.36, P=0.005). The direct bilirubin was 5.01, 4.67, 4.47 and 4.35mmol/L (F=4.63, P=0.003).The indirect bilirubin was 8.25, 7.69, 7.60 and 7.37 μmol/L(F=2.96, P=0.033). Pearson correlation analysis showed that total bilirubin concentration (r=-0.241, P<0.01), direct bilirubin concentration (r=-0.23,P<0.01), and indirect bilirubin concentration (r=-0.21,P<0.01) were inversely correlated with duration of diabetes. Multiple linear regression analysis showed that an increment of one year in diabetes duration was associated with 0.087mmol/L decrease in total bilirubin, 0.037mmol/L in direct bilirubin and 0.051mmol/L in indirect bilirubin separately. Conclusion Serum bilirubin concentration is negatively

  5. Vascular cognitive impairment and dementia.

    Science.gov (United States)

    Gorelick, Philip B; Counts, Scott E; Nyenhuis, David

    2016-05-01

    Vascular contributions to cognitive impairment are receiving heightened attention as potentially modifiable factors for dementias of later life. These factors have now been linked not only to vascular cognitive disorders but also Alzheimer's disease. In this chapter we review 3 related topics that address vascular contributions to cognitive impairment: 1. vascular pathogenesis and mechanisms; 2. neuropsychological and neuroimaging phenotypic manifestations of cerebrovascular disease; and 3. prospects for prevention of cognitive impairment of later life based on cardiovascular and stroke risk modification. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock. PMID:26704177

  6. [Multilingualism and specific language impairment].

    Science.gov (United States)

    Arkkila, Eva; Smolander, Sini; Laasonen, Marja

    2013-01-01

    Specific language impairment is one of the most common developmental disturbances in childhood. With the increase of the foreign language population group an increasing number of children assimilating several languages and causing concern in language development attend clinical examinations. Knowledge of factors underlying the specific language impairment and the specific impairment in general, special features of language development of those learning several languages, as well as the assessment and support of the linguistic skills of a multilingual child is essential. The risk of long-term problems and marginalization is high for children having specific language impairment.

  7. 新生儿小时胆红素百分位曲线图预测高胆红素血症的研究进展%Prediction of neonatal hyperbilirubinemia by the hour-specific bilirubin nomogram

    Institute of Scientific and Technical Information of China (English)

    孙小凡

    2015-01-01

    Neonatal hyperbilirubinemia,a common disease in the newborn period,account for about 8% ~ 11% in all newborns.Without getting proper controlling or being treated on time,severe hyperbilirubinemia may develop bilirubin encephalopathy leading to nerve damage and functional disability,which causes society and family problems.The hour-specific bilirubin nomogram is used to evaluate neonatal bilirubin discharge risks,intervention and follow-up.All pediatricians all over the world are focus on reducing the occurrence of bilirubin encephalopathy.In this study,we reviewed all researches about predicting the occurrence of neonatal hyperbilirubinemia after discharge using the hour-specific bilirubin nomogram which will better guide clinical diagnosis and treatment.%新生儿高胆红素血症是新生儿期的常见病,约8%~11%的新生儿发生严重的高胆红素血症.严重高胆红素血症如果没有得到及时控制和治疗,可发展为胆红素脑病,导致神经损害和功能残疾.利用小时胆红素百分位曲线图对新生儿进行出院的风险预测、干预及随访,降低胆红素脑病的发生,是国内外儿科医生关注的焦点.该文就各国制备的小时胆红素百分位曲线预测出院后高胆红素血症发生风险的研究进展作一综述,以便于小时胆红素百分位曲线更好地指导临床诊疗.

  8. Occupational exposure to manganese.

    Science.gov (United States)

    Sarić, M; Markićević, A; Hrustić, O

    1977-05-01

    The relationship between the degree of exposure and biological effects of manganese was studied in a group of 369 workers employed in the production of ferroalloys. Two other groups of workers, from an electrode plant and from an aluminium rolling mill, served as controls. Mean manganese concentrations at work places where ferroalloys were produced varied from 0-301 to 20-442 mg/m3. The exposure level of the two control groups was from 2 to 30 microgram/m3 and from 0-05 to 0-07 microgram/m3, in the electrode plant and rolling mill respectively. Sixty-two (16-8%) manganese alloy workers showed some signs of neurological impairment. These signs were noticeably less in the two control groups (5-8% and 0%) than in the occupationally exposed group. Subjective symptoms, which are nonspecific but may be symptoms of subclinical manganism, were not markedly different in the three groups. However, in the manganese alloy workers some of the subjective symptoms occurred more frequently in heavier smokers than in light smokers or nonsmokers. Heavier smokers engaged in manganese alloy production showed some of the subjective symptoms more often than heavier smokers from the control groups.

  9. Effects of Perfluorooctanoic Acid on Mouse Mammary Gland Development and Differentiation Resulting from Cross-Foster and Restricted Gestational Exposures

    Science.gov (United States)

    The adverse consequences of developmental exposures to perfluorooctanoic acid (PFOA) have been established, and include impaired development of the offspring mammary gland (MG). However, the relationship between the timing or route of exposure, and the phenotypic consequences in ...

  10. 亲和膜配基的结构和密度对胆红素吸附的影响%Effect of ligand composition and ligand density of affinity membrane on bilirubin removal

    Institute of Scientific and Technical Information of China (English)

    鞠佳; 聂飞; 段志军; 贺高红

    2013-01-01

    High concentration of bilirubin may cause neurotoxicity, permanent brain damage, and even death in severe cases. It is difficult to remove bilirubin from serum by circulated adsorption, because bilirubin can be tightly bound with albumin as a complex in human serum. The albumin in the complex has a larger volume than that of bilirubin, which results in high steric hindrance of adsorption or displacement of bilirubin. In order to enhance serum bilirubin adsorption capacity, five kinds of amines and eight kinds of amino acids as specific ligands were immobilized on cellulose acetate (CA) /polyethyleneimine (PEI) membrane via the glutaraldehyde modification method. Experimental results indicated that although the primary amine contents of modified membranes were only one third of CA/PEI membrane, bilirubin adsorption capacities of four kinds of modified membranes increased by more than 100%. Moreover, the adsorption selectivity of the four modified membranes for bilirubin/human albumin pair was greater than that of CA/ PEI membrane. Prolongation of the spacer and immobilization of specific ligand could be the cause of such results. Ligand composition had a significant influence on bilirubin adsorption capacity. The ligands containing hydrophobic and primary amino groups could enhance bilirubin adsorption capacity, and the ligands with carboxyl radicals could decrease bilirubin adsorption capacity of the modified membrane. Moreover, ligand density, ligand steric hindrance, and other factors could also influence bilirubin adsorption capacity. In the experiments, the ligands containing high steric hindrance groups, such as phenyl groups had a negative effect on bilirubin adsorption capacity of the modified membrane, and its bilirubin adsorption capacity could not be enhanced via increasing ligand density. However, bilirubin adsorption capacity of the membrane modified with low steric hindrance ligand, for example hexamethylene-diamine (3-HMD) -modified membrane

  11. Astrocytes Underlie Neuroinflammatory Memory Impairment

    OpenAIRE

    Osso, LA; Chan, JR

    2015-01-01

    © 2015 Elsevier Inc. All rights reserved. Neuroinflammation is being increasingly recognized as a potential mediator of cognitive impairments in various neurological conditions. Habbas et al. demonstrate that the pro-inflammatory cytokine tumor necrosis factor alpha signals through astrocytes to alter synaptic transmission and impair cognition in a mouse model of multiple sclerosis.

  12. Optimal time of phototherapy for newborns whose total bilirubin ranges from 75 th to 95th percentile in the hour - specific serum bilirubin nomogram%对总胆红素位于小时胆红素第75-95百分位的新生儿光疗时机的研究

    Institute of Scientific and Technical Information of China (English)

    韩金粉; 彭艳松; 刘学工

    2012-01-01

    Objective To study the optimal time of phototherapy for newborns (gestational age≥36 weeks and birth weight≥2500 g) whose total bilirubin ranges from 75th to 95th percentile in the hour - specific serum bilirubin nomogram.Methods The hour - specific serum bilirubin nomogram recommended by America in 2004 was used in this study.Newborns total serum bilirubin (TSB) values from 75th to 95th percentile were divided into 2 groups based on high -risk factors of jaundice inside 72 hours after birth:the observed group with high - risk factors of jaundice and the CK group without them.The number of TSB of the newborns TSB beyond 95th percentile outside 72 h after birth was researched in the two groups.Results Before discharge,total serum bilirubin (TSB) values of 12.8% (5/39) infants were in the high risk zone ( >95th percentile) in the CK group and of 32.2% (10/31) were in that zone in the observed group.The difference was significant ( x2 =3.876,P < 0.05 ).Conclusions Phototherapy should begin inside 72 hours after birth for the newborns with high - risk factors of jaundice and (TSB) values from 75 th to 95 th percentile,and the primary diseases should be treated actively.%目的 探讨胎龄≥36周、体质量≥2500 g、总胆红素值位于小时胆红素百分位值列线图第75~95百分位的新生儿合理光疗时机.方法 利用美国2004年推荐使用的小时胆红素百分位值列线图,将生后72 h内总胆红素值位于第75 ~95百分位的新生儿,分为有黄疸高危因素的研究组及无黄疸高危因素的对照组,比较两组新生儿生后72 h后胆红素上升至第95百分位病例数的统计学差异.结果 对照组39倒,生后72 h后总胆红素上升至第95百分位5倒,发生率为12.8% (5/39);研究组31例,生后72 h后总胆红素上升至第95百分位10例,发生率为32.2%( 10/31),差异有统计学意义(x2=3.876,P< 0.05).结论 对生后72 h内总胆红素值位于小时胆

  13. PREPARATION AND ADSORPTION PROPERTIES OF BILIRUBIN ADSORBENTS WITH DIFFERENT LIGANDS BASED ON SEPHAROSE CL-4B%胆红素吸附剂功能基组成及其吸附特性研究

    Institute of Scientific and Technical Information of China (English)

    王智; 陈书博; 徐丽; 谢健; 贾凌云

    2011-01-01

    为了获得性能较佳的胆红素吸附剂,本研究考察了功能基种类、链长、偶联密度等因素对吸附剂吸附性能的影响.结果表明,当功能基具有足够的链长,与胆红素相似的疏水性及较高的偶联密度时,能够提高吸附剂的胆红素吸附能力.实验表明,链长21个原子、偶联73μmol/mL正丁胺的吸附剂对胆红素的吸附能力最强,在30℃、300mg/L的白蛋白结合胆红素溶液中,吸附1h即达到平衡,胆红素吸附量达到3.01 mg/mL (90.3mg/g干重);较高的温度有利于其对胆红素的吸附.50mL材料对500mL实际病人血浆动态吸附2.5h,总胆红素(277.4mg/L)去除率达到55.2%,同时对血浆蛋白的吸附较低.所有结果显示该吸附剂具有很强的实际应用的潜力.%A series of bilirubin adsorbents with different ligand type, length and density were prepared by activation of Sepharose CL-4B and their adsorption capacities to bilirubin were measured in static adsorption experiments. The results showed that the structure and properties of ligands, such as sufficient spacer-length, higher grafting density on the adsorbent and the similar hydrophobicity with bilirubin, were helpful to improve adsorption capacity of bilirubin. These experiments provided some ideas for designing new adsorbents. Among these adsorbents, the adsorbent with 73μmol/mL butylamine and 23-atom spacer showed the strongest adsorption ability to bilirubin in BSA-bilirubin solution, which could reach the adsorption balance at 30°C in lh, and got binding capacity of 3.01mg/mL gel. Moreover, higher temperature was more favorable to the adsorption of bilirubin. The in vitro hemoperfusion experiments were carried out by adding 50mL adsorbent into 500mL patient's plasma and 55.2% of bilirubin (277.4mg/L) was removed after 2.5h, and at the same time, adsorption for plasma proteins was low. These results indicated that the Butylamine-Sepharose adsorbents could be a potential choice for specific

  14. Quantitative olfactory disorders and occupational exposure to phenolic resins

    OpenAIRE

    Matteo Riccó; Carlo Signorelli; Enrico Pistelli; Silvia Cattani

    2016-01-01

    Background: To investigate whether exposure to phenolic resins (PR) is associated with quantitative olfactory disorders (QOD), a cross-sectional study of self-reported olfactory impairment (SROI) was performed in occupationally exposed subjects. Material and Methods: Sixty-six workers (45 males, 21 females) at the age (mean ± standard deviation) of 39.8±10.15 years old were divided into 3 exposure groups on the basis of biological exposure indices (BEI) for urinary phenols. It was asked wheth...

  15. PROPYLTHIOURACIL (PTU)-INDUCED HYPOTHYROIDISM REDUCES FIELD POTENTIAL AMPLITUDE BUT DOES NOT IMPAIR DENTATE GYRUS LTP IN VIVO.

    Science.gov (United States)

    Developmental exposure to hypothyroid-inducing agents leads to reductions in body weight, alterations in hippocampal structure, and impaired performance on a variety of behavioral learning tasks. Electrophysiological properties of the hippocampus in hypothyroid animals, however...

  16. 胆红素在纳米CdSe表面吸附行为的QCM研究%Investigation of Absorption Behavior of Bilirubin on nanocrystalline CdSe microlayers using QCM

    Institute of Scientific and Technical Information of China (English)

    刘国聪; 梁达文; 庞起; 董辉; 曾楚杰; 韦庆敏; 段学臣

    2007-01-01

    The absorption behavior of bilirubin on nanocrystal CdSe was investigated in detail using quartz crystal microbalance (QCM). The adsorption kinetic parameters estimated from the in situ frequency measurement is (1.5 ± 0.32)×106 M-1(mean ± S.D).with the present method, Impedance characteristic of CdSe suspension and response of the Piezoelectric crystal Impedance (PCI)sensor were detailedly analysed. It was found that the adsorption of bilirubin on the surface of CdSe electrodes strongly depended on a few influencing factors such as pH,solution concentration temperature,and solution ionicstrength.The results indicate the amount of adsorbed bilirubin increased with increasing of hydroxyl ions, bilirubin concentration and higher solution ionic strength, but small at higher temperature. The sensors based on the CdSe microlavers show especial sensitive to bilirubin. QCM measurement provides a facile method for monitoring the adsoption/desorption process of bilirubin on nanocrystalline CdSe.%用石英微天平技术详细研究了胆红素在纳米CdSe晶体表面上的吸附行为.从频率测试中得出的吸附动力学参数约是(1.5±0.32)×106 M-1(平均数±相对误差).此法细致研究了CdSe悬浮液的阻抗性能和压电性能.实验中发现胆红素在CdSe纳米晶上的吸附作用受体系温度、pH和离子强度等因素影响:较高温度不利于胆红素的吸收,但随着pH、离子强度和胆红素浓度的增大胆红素的吸附量明显增大.研究表明基于CdSe纳米组装的传感器对胆红素十分敏感.此技术为分析胆红素在CdSe纳米拓扑界面的吸附与解吸机制提供了有效的方法.

  17. Study on serum levels of lipids and bilirubin in patients with coronary heart disease%冠心病患者血脂和胆红素变化的研究

    Institute of Scientific and Technical Information of China (English)

    韦光海

    2008-01-01

    Objective To investigate the relationship of the levels of serum lipids and bilirubin with occurrence and development of coronary heart disease (CHD). Methods 139 CHD patients and 118 healthy controls were involved in the study. The serum levels of triglyeride (TG), total cholester-ol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C)and bilirubin were measured and compared. Results In CHD group, the levels of TG, TC, LDL-C,TG, HDL-C, LDL-C and HDL-C were significantly elevated, while the levels of HDL-C, total biliru-bin (Tbil) and indirect bilirubin (Ibil) were markedly declined. The changes were associated with the severity of coronary artery disease. There wasn't significant difference of direct bilirubin level between CHD group and healthy control group. Conclusion Blood lipid abnormality and declination of bilirubin level are closely associated with coronary heart disease. It is possible to prevent the occurrence of car-diovascular event by early intervention.%目的 探讨血脂、胆红素与冠心病发生、发展的关系.方法 随机抽取139例冠心病患者和118例健康者进行血清甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)及胆红素水平检测与对比分析.结果 冠心病组患者TG、TC、LDL-C、TG/HDL-C、LDL-C/HDL-C显著升高(P0.05).结论 血脂异常和胆红素水平降低与冠心病密切相关.早期干预有可能预防心血管事件的发生.

  18. 经皮测胆红素在新生儿高胆红素血症中的应用价值%The Application Value of Transcutaneous Bilirubin in Neonatal Hyperbilirubinemia

    Institute of Scientific and Technical Information of China (English)

    周琼; 张飞忠

    2014-01-01

    Objectiv:To investigate the application value of transcutaneous bilirubin (TCB) in neonatal hyperbilirubinemia. Methods:215 cases of children with hyperbilirubinemia were dynamically tested by transcutaneous bilirubin method and blood bilirubin method at 6h, 12h, 2d, 4d, 7d and other time points respectively after the admission, and the correlation of the two sets of data was compared.Results:the values measured by transcutaneous bilirubin method and blood bilirubin method at 6h, 12h, 2d, 4d, 7d and other time points showed a linear correlation relationship (P<0.05).Conclusion:TCB has many advantages such as non-invasive, repeatable testing, easy to perform, rapid detection, dynamic monitoring of neonatal bilirubin changes, etc. it deserves clinical application.%目的::探讨经皮测胆红素(TCB)在新生儿高胆红素血症中的应用价值。方法:在入院第6h、12h、2d、4d、7d等时间点采用经皮测胆红素和经血测胆红素方法对215例高胆红素血症患儿进行动态检测,比较两组数据的相关性。结果:经皮测胆红素值和经血测胆红素值在新生儿入院第6h、12h、2d、4d、7d等时间点呈直线相关性关系(P<0.05)。结论:TCB具有无创伤性、可重复多次检测、操作简单易学、检测迅速、可动态监测新生儿胆红素变化情况等优点,值得临床推广使用。

  19. Impaired Striatal Akt Signaling Disrupts Dopamine Homeostasis and Increases Feeding

    OpenAIRE

    Nicole Speed; Christine Saunders; Davis, Adeola R.; W Anthony Owens; Heinrich J.G. Matthies; Sanaz Saadat; Jack P Kennedy; Vaughan, Roxanne A.; Neve, Rachael L.; Lindsley, Craig W.; Russo, Scott J.; Daws, Lynette C.; Niswender, Kevin D.; Aurelio Galli

    2011-01-01

    BACKGROUND: The prevalence of obesity has increased dramatically worldwide. The obesity epidemic begs for novel concepts and therapeutic targets that cohesively address "food-abuse" disorders. We demonstrate a molecular link between impairment of a central kinase (Akt) involved in insulin signaling induced by exposure to a high-fat (HF) diet and dysregulation of higher order circuitry involved in feeding. Dopamine (DA) rich brain structures, such as striatum, provide motivation stimuli for fe...

  20. Management of impaired fracture healing: Historical aspects

    OpenAIRE

    Gajdobranski Đorđe; Micić Ivan; Mitković Milorad B.; Mladenović Desimir; Milankov Miroslav

    2005-01-01

    Introduction Establishing continuity of long bones in cases of impaired bone healing and pseudo-arthrosis is one of the most complex problems in orthopedics. Impaired bone healing The problem of impaired fracture healing is not new. As in other areas of human life, the roots of modern treatment of impaired bone healing lie in ancient medicine. A relatively high percentage of impaired bone healing, as well as unsatisfactory results of standard therapies of impaired bone healing and pseudoarthr...

  1. EEG in Specific Language Impairment

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2008-11-01

    Full Text Available The value of routine wake electroencephalography in children with specific language impairment was reviewed retrospectively in 111 children examined over a 10-year interval at Montreal Children’s Hospital, Quebec, Çanada.

  2. Intracerebral hemorrhage and cognitive impairment.

    Science.gov (United States)

    Xiong, Li; Reijmer, Yael D; Charidimou, Andreas; Cordonnier, Charlotte; Viswanathan, Anand

    2016-05-01

    Vascular cognitive impairment and vascular dementia are composed of cognitive deficits resulted from a range of vascular lesions and pathologies, including both ischemic and hemorrhagic. However the contribution of spontaneous intracerebral hemorrhage presumed due to small vessel diseases on cognitive impairment is underestimated, in contrast to the numerous studies about the role of ischemic vascular disorders on cognition. In this review we summarize recent findings from clinical studies and appropriate basic science research to better elucidate the role and possible mechanisms of intracerebral hemorrhage in cognitive impairment and dementia. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock.

  3. [Cognitive Impairment in Multiple Sclerosis].

    Science.gov (United States)

    Niino, Masaaki; Miyazaki, Yusei

    2016-04-01

    While cognitive impairment is a major symptom of multiple sclerosis (MS), it is commonly overlooked. This may be explained by the fact that it is difficult to evaluate cognitive function in patients with MS using screening batteries for the detection of dementia such as the mini-mental state examination. Further more, cognitive impairment in MS typically involves domain-specific deficits such as imparement of sustained attention and information processing speed rather than global cognitive decline. Cognitive impairment may influence the daily living and social lines of affected patients. This review discusses the characteristics of cognitive impairment, appropreate tests to evaluate its symptoms, and the current status of clinical trials for the treatment of MS. PMID:27056855

  4. ENVIRONMENTAL INJUSTICE AND MOBILITY IMPAIRMENT

    Directory of Open Access Journals (Sweden)

    Michael Cahill

    2013-06-01

    Full Text Available The study of mobility is a growth area in the social sciences.  The car system (automobility has had as one of its consequences reduced opportunities for mobility impaired people to walk in their local environment. Immobility has resulted for many people with disabilities. Despite the promotion of physical activity by public health guidance local environments are often hazardous for mobility impaired people.  In particular, there is a problem with cars parking on pavements and pavement cycling.

  5. Vascular contributions to cognitive impairment

    OpenAIRE

    Wright, Clinton B.; Flores, Alan

    2015-01-01

    Unlike many neurodegenerative causes of cognitive impairment and dementia, vascular damage is preventable. Despite the heterogeneity of vascular cognitive impairment (VCI) and the complexity of its clinical presentations, the potential for limiting progression and changing the trajectory of damage makes it all the more important for physicians to be educated about the syndrome and to remain vigilant when taking care of patients. In this review, we outline an approach to patients with possible...

  6. Chemistry for the Visually Impaired

    Science.gov (United States)

    Ratliff, Judy L.

    1997-06-01

    Methods used to try to provide a valuable experience for visually impaired students in a general education or an introductory chemistry class are discussed. Modifications that can be made cheaply and with little time commitment which will allow visually impaired students to participate productively in the laboratory are examined. A conductivity tester that cost less than $4.00 to construct, is easy to assemble, very rugged, and provides a great deal of entertainment for sighted and non-sighted students is described.

  7. 血清胆红素和血脂对冠心病发生的作用%Effection of serum bilirubin and serum lipid on coronary heart disease

    Institute of Scientific and Technical Information of China (English)

    李现立; 郑晓晖; 郝增光; 杨睿; 葛慧敏

    2010-01-01

    目的 探讨血清胆红素和血脂在冠心病发生中的作用.方法 75例冠心病患者被分为高脂血症组(46例)和非高脂血症组(29例),35例正常健康成人作为对照组,分别测定血清总胆红素(TBIL)、直接胆红素(DBIL)、间接胆红素(IBIL)以及总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL)和高密度脂蛋白(HDL)水平等指标作对比分析.结果 高脂血症组TBIL、DBIL、IBIL均低于非高脂血症组和正常对照组,差异有统计学意义(P<0.05);非高脂血症组血清胆红素水平低于正常对照组,差异有统计学意义(P<0.05).高脂血症组同非高脂血症组、正常对照组比较,TC、TG和LDL增高,HDL降低,差异有统计学意义(P<0.05);非高脂血症组同正常对照组比较,TC、TG和LDL增高,HDL降低,但差异无统计学意义(P>0.05).结论 低胆红素水平在高脂血症和非高脂血症的冠心病发生中起着重要的作用,是冠心病的独立危险因素.%Objective To investigate the effection of serum bilirubin and serum lipid on coronary heart disease (CHD). Methods Seventy -five patients with CHD group were divided into hyperlipidemia group(46 cases) and non- hyperlipidemia group (29 cases),35 healthy controls (healthy control group)were enrolled in the study. Serum total bilirubin (TBIL), direct bilirubin (DBIL), indirect bilirubin (IBIL)serum triglycride ( TG), total cholestrol ( TC ), low density lipoprotein (LDL), high density lipoprotein (HDLand serum lipid were examined for all subiects,and then the results were compared and analyzed. Results The contents of serum TBIL, direct bilirubin (DBIL), indirect bilirubin (IBIL)were lower in hyperlipidemia group than those of non - hyperlipidemia and healthy control group, the difference was significant (P <0. 05 ). The contents of serum bilirubin were lower in non - hyperlipidemia group than those of healthy control group, the difference was significant( P < 0.05 ). TC,TG and LDL were

  8. Determination of Effect of Low Dose Vs Moderate Dose of Clofibrate on the Decreasing in Serum Bilirubin Level in the Term Healthy Neonate

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    Mohammad Ashkan Moslehi

    2007-05-01

    Full Text Available Objective: This study was performed to determine the effect of low doses (25 mg/Kg vs. moderate doses (50 mg/Kg of clofibrate in treatment of non-hemolytic hyperbilirubin¬emia in healthy term neonates. Material & Methods: A clinical randomized controlled trial was performed in three groups of healthy term neonates. One group was treated with a single low dose of clofibrate (25 mg/Kg while another group received a single moderate dose (50mg/kg both orally plus phototherapy; the results were compared with those of a control group that received only phototherapy. Findings: The mean total serum bilirubin (TSB levels of 12th and 24th hours were significantly lower in the two clofibrate-treated groups as compared with the control group (P=0.002 and P=0.003, respectively. There was no statistically significant difference between the mean of TSB levels in the two clofibrate-treated groups. Treatment with clofibrate also resulted in a shorter duration of jaundice and a decreased use of phototherapy (P=0.01. No side effects were observed. Conclusion: The present study demonstrated that there was no significant difference between a low (25mg/Kg and moderate (50mg/Kg doses of clofibrate in reducing TSB levels and also decreased need of phototherapy in healthy breastfed term newborns with marked hyperbilirubin¬emia (TSB>16 mg/dL.

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

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    Zhangbin Yu

    2014-06-01

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

  10. Development and validation of serum bilirubin nomogram to predict the absence of risk for severe hyperbilirubinaemia before discharge: a prospective, multicenter study

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    Romagnoli Costantino

    2012-02-01

    Full Text Available Abstract Background Early discharge of healthy late preterm and full term newborn infants has become common practice because of the current social and economic necessities. Severe jaundice, and even kernicterus, has developed in some term infants discharged early. This study was designed to elaborate a percentile-based hour specific total serum bilirubin (TSB nomogram and to assess its ability to predict the absence of risk for subsequent non physiologic severe hyperbilirubinaemia before discharge. Methods A percentile-based hour-specific nomogram for TSB values was performed using TSB data of 1708 healthy full term neonates. The nomogram's predictive ability was then prospectively assessed in five different first level neonatal units, using a single TSB value determined before discharge. Results The 75 th percentile of hour specific TSB nomogram allows to predict newborn babies without significant hyperbilirubinemia only after the first 72 hours of life. In the first 48 hours of life the observation of false negative results did not permit a safe discharge from the hospital. Conclusion The hour-specific TSB nomogram is able to predict all neonates without risk of non physiologic hyperbilirubinemia only after 48 to 72 hours of life. The combination of TSB determination and risk factors for hyperbilirubinemia could facilitate a safe discharge from the hospital and a targeted intervention and follow-up.

  11. Enhancement of the performances of a single concentric glucose/O{sub 2} biofuel cell by combination of bilirubin oxidase/Nafion cathode and Au-Pt anode

    Energy Technology Data Exchange (ETDEWEB)

    Habrioux, A.; Servat, K.; Kokoh, K.B. [LACCO ' ' Equipe Electrocatalyse' ' , UMR 6503 CNRS-Universite de Poitiers, 40 Avenue du Recteur Pineau, 86022 Poitiers (France); Tingry, S. [Institut Europeen des Membranes, UMR 5635, ENSCM-UMII-CNRS Place Eugene Bataillon, CC 047, 34095 Montpellier, Cedex 5 (France)

    2009-01-15

    This work deals with a novel preparation method of bilirubin oxidase/2,2'-azinobis-3-ethylbenzothiazoline-6-sulfonic acid electrode. The enzyme and its mediator were adsorbed on carbon Vulcan XC-72R before their immobilization into a Nafion {sup registered} matrix. Promising results were obtained when this biocathode was associated with Au{sub 70}Pt{sub 30} nanoparticles as anode in a single concentric glucose/O{sub 2} biofuel cell (BFC). The latter BFC delivered at 37 C a power density of 90 {mu}W cm{sup -2} for a cell voltage of 0.4 V in phosphate buffer (pH 7.4) containing 0.01 M glucose. Moreover, the electrical performances were increased with the concentration of glucose by generating up to 190 {mu}W cm{sup -2} for a cell voltage of 0.52 V when the concentration of the renewable fuel reached 0.7 M. (author)

  12. [What is impaired consciousness? Revisiting impaired consciousness as psychiatric concept].

    Science.gov (United States)

    Kanemoto, Kousuke

    2004-01-01

    For decades, psychiatrists have considered that concepts of impaired consciousness in the study of psychiatry were inconsistent with those applied in the field of neurology, in which the usefulness of the concept of consciousness has long been seriously doubted. Gloor concluded that the concept of consciousness does not further the understanding of seizure mechanisms or brain function, which is the current representative opinion of most epileptologists. Loss of consciousness tends to be reduced to aggregates of individual impairments of higher cognitive functions, and the concept of consciousness is preferably avoided by neurologists by assigning various behavioral disturbances during disturbed consciousness to particular neuropsychological centers. In contrast, psychiatrists, especially those in Europe, are more likely to include phenomena involving problems related to phenomenological intentionality in impaired consciousness. For the present study, we first divided consciousness into vigilance and recursive consciousness, and then attempted to determine what kind of impaired consciousness would be an ideal candidate to represent pure disturbance of recursive consciousness. Then, 4 patients, 1 each with pure amnestic states followed immediately by complex partial seizures, an akinetic mutistic state caused by absence status, and mental diplopia as a manifestation of postictal psychosis, as well as a patient with Alzheimer's disease who gracefully performed Japanese tea ceremony, were studied. Based on our findings, we concluded that impaired consciousness as a generic term in general medicine does not indicate any unitary entity corresponding to some well-demarcated physiological function or constitute a base from which recursive consciousness emerges as a superstructure. From that, we stressed that a pure form of impairment of recursive consciousness could occur without the impaired consciousness named generically in general medicine. Second, following

  13. [What is impaired consciousness? Revisiting impaired consciousness as psychiatric concept].

    Science.gov (United States)

    Kanemoto, Kousuke

    2004-01-01

    For decades, psychiatrists have considered that concepts of impaired consciousness in the study of psychiatry were inconsistent with those applied in the field of neurology, in which the usefulness of the concept of consciousness has long been seriously doubted. Gloor concluded that the concept of consciousness does not further the understanding of seizure mechanisms or brain function, which is the current representative opinion of most epileptologists. Loss of consciousness tends to be reduced to aggregates of individual impairments of higher cognitive functions, and the concept of consciousness is preferably avoided by neurologists by assigning various behavioral disturbances during disturbed consciousness to particular neuropsychological centers. In contrast, psychiatrists, especially those in Europe, are more likely to include phenomena involving problems related to phenomenological intentionality in impaired consciousness. For the present study, we first divided consciousness into vigilance and recursive consciousness, and then attempted to determine what kind of impaired consciousness would be an ideal candidate to represent pure disturbance of recursive consciousness. Then, 4 patients, 1 each with pure amnestic states followed immediately by complex partial seizures, an akinetic mutistic state caused by absence status, and mental diplopia as a manifestation of postictal psychosis, as well as a patient with Alzheimer's disease who gracefully performed Japanese tea ceremony, were studied. Based on our findings, we concluded that impaired consciousness as a generic term in general medicine does not indicate any unitary entity corresponding to some well-demarcated physiological function or constitute a base from which recursive consciousness emerges as a superstructure. From that, we stressed that a pure form of impairment of recursive consciousness could occur without the impaired consciousness named generically in general medicine. Second, following

  14. 吸附于银胶颗粒表面的胆红素及胆绿素分子吸附取向研究%The Study of Orientations of Bilirubin and Biliverdin by Surface-enhanced Raman Spectroscopy

    Institute of Scientific and Technical Information of China (English)

    胡军; 方清; 盛蓉生; 徐知三; 曾云鹗

    2001-01-01

    胆红素、胆绿素作为重要的生物小分子被广泛研究。本文采用表面增强拉曼光谱技术获得了胆红素和胆绿素分子吸附于银胶颗粒表面的拉曼光谱。通过对其谱带的指认分析,表明胆红素形成了三对内氢键,并以其两个吡咯亚甲基酮环沿银胶颗粒表面切向方向镶嵌在银胶颗粒上,而胆绿素则以顺式-顺式-顺式构型平躺吸附于银胶颗粒表面。%The surface-enhanced Raman spectra of bilirubin and biliverdin were obtained.By the bands analysis of the spectra,the orientation of bilirubin and biliverdin on the surface of silver colloid was discussed.In such case,the bilirubin was adsorbed on the silver colloid particle with the two planar pyrromethenone groups intercalated into the globe silver colloid particle,however,the biliverdin might lie flat on the surface of silver colloid with syn-synsyn conformation.

  15. SERUM TOTAL BILIRUBIN, NOT CHOLELITHIASIS, IS INFLUENCED BY UGT1A1 POLYMORPHISM, ALPHA THALASSEMIA AND S GENOTYPE: FIRST REPORT ON COMPARISON BETWEEN ARAB-INDIAN AND AFRICAN S GENES

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    Said Y ALkindi

    2015-10-01

    Full Text Available Background: We explored the potential relationship between steady state serum bilirubin levels and the incidence of cholelithiasis in the context of UGT1A1 gene A(TAnTAA promoter polymorphism in Omani sickle cell anemia (SCA patients, homozygotes for African (Benin and Bantu and Arab-Indian bS haplotypes, but sharing the same microgeographical environment and comparable life style factors.   Methods: 136 SCA patients were retrospectively studied in whom imaging data including abdominal CT scan, MRI or Ultrasonography was routinely available. Available data on the mean steady state hematological/biochemical parameters (n=136,  bs haplotypes(n=136, a globin gene status (n=105 and UGT1A1 genotypes(n=133 were reviewed from the respective medical records.   Results: The mean serum total bilirubin level was significantly higher in the homozygous UGT1A1(AT7 group as compared to  UGT1A1(AT6 group. Strikingly, cholelithiasis was not influenced by age, gender, alpha globin genotype or bS haplotypes in this SCA cohort.   Conclusion: As observed in other population groups, the UGT1A1 (AT7 homozygosity was significantly associated with raised serum total bilirubin level, but the prevalence of gallstones in the Omani SCA patients was not associated with a thalassaemia, UGT1A1 polymorphism, or bs haplotypes.

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

    Science.gov (United States)

    Korani, Aazam; Salimi, Abdollah

    2013-12-15

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

  17. On the impact of oxytocin on high neonatal bilirubin levels, clinical studies%催产素对新生儿高胆红素血症影响的临床研究

    Institute of Scientific and Technical Information of China (English)

    罗嫚丽

    2016-01-01

    Objective to explore the application of oxytocin during labor and maternal high different dose of oxytocin on neonatal bilirubin hematic disease, provide guidance for clinical. Methods to select 339 full-term healthy newborns born to our hospital patients as the research object, according to whether or not to use in the process of childbirth oxytocin is divided into two groups, 223 cases of patients who did not use the oxytocin neonatal as control group, and use of oxytocin, 116 cases of neonatal as observation group, and all 3, 5, and 7 days after birth detect neonatal bilirubin, was born in 7 d after record high neonatal bilirubin levels and the incidence of asphyxia. Results in the control group after the birth of blood bilirubin value ex-ists significant difference, and after the birth of 3 d, 5 d after birth no difference, after the birth of the 7 d significantly reduced, the observation group after the birth of blood bilirubin value exists significant difference, and after the birth of 3 d, 5 d after birth there is significant difference, after the birth of the 7 d significantly reduced, between the two groups in 3 d, 5 d, 7 d after birth blood bilirubin value exists significant difference; In 3 d after birth, the different dose of oxytocin blood bilirubin value differ-ences between groups, 5 IU group and 10 IU group is significantly higher than 1.5 IU group and 2.5 IU group, 5 d and 7 d after birth, blood bilirubin values between different dose of oxytocin group differences, with the increase of dosage, blood bilirubin values significantly increased; Newborn on the incidence of high blood bilirubin, control group was 21.97% (49/223), the ob-servation group of newborns was 37.93% (44/116), there were significant differences; Newborn on the incidence of asphyxia, control group was 4.04% (9/223), the observation group of newborns was 14.66% (17/116), there were significant differences.Conclusion pregnant women in childbirth using oxytocin but high neonatal

  18. Assessing functional impairment in individuals with mild cognitive impairment

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    Patrícia Belchior

    2016-04-01

    Full Text Available To date, there is no consensus on how to assess functional impairment in individuals with mild cognitive impairment (MCI, and this lack of consensus is reflected in the clinical practice. Since the criterion used in the literature is very vague, clinicians are still left without much guidance in this area. Thus, the main goal of this study was to examine how functional impairment in individuals with MCI has been assessed in the literature. An electronic database search strategy was developed in consultation with an experienced librarian. Four databases (CINAHL, PsycINFO, PubMed, and MEDLINE were searched from 2000 to May 2014 to provide a comprehensive coverage of the literature. The literature search yielded 14 tools that assessed functional impairment in MCI. Among those, nine tools were performance-based measures in which participants were observed while executing a task in a simulated environment using real life material. In terms of questionnaires (either informant- or self-reports, five tools were found. Different functional domains have been assessed in each tool. According to this review, the characteristics of the instruments used in the literature to assess functional impairment in individuals with MCI vary greatly. Nonetheless, results of this study allow clinicians to make better-informed decisions when choosing a functional assessment for this population.

  19. Patterns of Semantic Memory Impairment in Mild Cognitive Impairment

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    Sven Joubert

    2008-01-01

    Full Text Available Although the semantic memory impairment has been largely documented in Alzheimer's disease, little is known about semantic memory in the preclinical phase of the disease (Mild Cognitive Impairment. The purpose of this study was to document the nature of semantic breakdown using a battery of tests assessing different aspects of conceptual knowledge: knowledge about common objects, famous people and famous public events. Results indicate that all domains of semantic memory were impaired in MCI individuals but knowledge about famous people and famous events was affected to a greater extent than knowledge about objects. This pattern of results suggests that conceptual entities with distinctive and unique properties may be more prone to semantic breakdown in MCI. In summary, results of this study support the view that genuine semantic deficits are present in MCI. It could be useful to investigate the etiological outcome of patients failing or succeeding at such tests.

  20. Occupational exposure to pesticides and respiratory health

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    Ali Mamane

    2015-06-01

    Full Text Available This article aims to review the available literature regarding the link between occupational exposure to pesticides and respiratory symptoms or diseases. Identification of epidemiological studies was performed using PubMed. 41 articles were included, 36 regarding agricultural workers and five regarding industry workers. Among the 15 cross-sectional studies focusing on respiratory symptoms and agricultural pesticide exposure, 12 found significant associations with chronic cough, wheeze, dyspnoea, breathlessness or chest tightness. All four studies on asthma found a relationship with occupational exposure, as did all three studies on chronic bronchitis. The four studies that performed spirometry reported impaired respiratory function linked to pesticide exposure, suggestive of either obstructive or restrictive syndrome according to the chemical class of pesticide. 12 papers reported results from cohort studies. Three out of nine found a significant relationship with increased risk of wheeze, five out of nine with asthma and three out of three with chronic bronchitis. In workers employed in pesticide production, elevated risks of chronic obstructive pulmonary disease (two studies out of three and impaired respiratory function suggestive of an obstructive syndrome (two studies out of two were reported. In conclusion, this article suggests that occupational exposure to pesticides is associated with an increased risk of respiratory symptoms, asthma and chronic bronchitis, but the causal relationship is still under debate.

  1. Language Impairment and Generative Analysis

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    Andrej Stopar

    2004-12-01

    Full Text Available This article deals with different types of language impairment from the perspective of generative grammar. The paper focuses on syntactic deficiencies observed in aphasic and SLI (specific language impairment patients. We show that the observed ungrammatical structures do not appear in a random fashion but can be predicted by that theory of universal sentence structure which posits a strict hierarchy of its constituent parts. The article shows that while the hierarchically lower elements remain unaffected, the higher positions in the hierarchy show various degrees of syntactic impairment. The paper supports the implementation of recent developments in the field of generative grammar with the intention of encouraging further theoretical, experimental and therapeutic research in the field.

  2. Mercury exposure in children: a review

    International Nuclear Information System (INIS)

    Exposure to toxic mercury (Hg) is a growing health hazard throughout the world today. Recent studies show that mercury exposure may occur in the environment, and increasingly in occupational and domestic settings. Children are particularly vulnerable to Hg intoxication, which may lead to impairment of the developing central nervous system, as well as pulmonary and nephrotic damage. Several sources of toxic Hg exposure in children have been reported in biomedical literature: (1) methylmercury, the most widespread source of Hg exposure, is most commonly the result of consumption of contaminated foods, primarily fish; (2) ethylmercury, which has been the subject of recent scientific inquiry in relation to the controversial pediatric vaccine preservative thimerosal; (3) elemental Hg vapor exposure through accidents and occupational and ritualistic practices; (4) inorganic Hg through the use of topical Hg-based skin creams and in infant teething powders; (5) metallic Hg in dental amalgams, which release Hg vapors, and Hg2+ in tissues. This review examines recent epidemiological studies of methylmercury exposure in children. Reports of elemental Hg vapor exposure in children through accidents and occupational practices, and the more recent observations of the increasing use of elemental Hg for magico-religious purposes in urban communities are also discussed. Studies of inorganic Hg exposure from the widespread use of topical beauty creams and teething powders, and fetal/neonatal Hg exposure from maternal dental amalgam fillings are reviewed. Considerable attention was given in this review to pediatric methylmercury exposure and neurodevelopment because it is the most thoroughly investigated Hg species. Each source of Hg exposure is reviewed in relation to specific pediatric health effects, particularly subtle neurodevelopmental disorders

  3. Cosmic radiation exposure and persistent cognitive dysfunction

    Science.gov (United States)

    Parihar, Vipan K.; Allen, Barrett D.; Caressi, Chongshan; Kwok, Stephanie; Chu, Esther; Tran, Katherine K.; Chmielewski, Nicole N.; Giedzinski, Erich; Acharya, Munjal M.; Britten, Richard A.; Baulch, Janet E.; Limoli, Charles L.

    2016-01-01

    The Mars mission will result in an inevitable exposure to cosmic radiation that has been shown to cause cognitive impairments in rodent models, and possibly in astronauts engaged in deep space travel. Of particular concern is the potential for cosmic radiation exposure to compromise critical decision making during normal operations or under emergency conditions in deep space. Rodents exposed to cosmic radiation exhibit persistent hippocampal and cortical based performance decrements using six independent behavioral tasks administered between separate cohorts 12 and 24 weeks after irradiation. Radiation-induced impairments in spatial, episodic and recognition memory were temporally coincident with deficits in executive function and reduced rates of fear extinction and elevated anxiety. Irradiation caused significant reductions in dendritic complexity, spine density and altered spine morphology along medial prefrontal cortical neurons known to mediate neurotransmission interrogated by our behavioral tasks. Cosmic radiation also disrupted synaptic integrity and increased neuroinflammation that persisted more than 6 months after exposure. Behavioral deficits for individual animals correlated significantly with reduced spine density and increased synaptic puncta, providing quantitative measures of risk for developing cognitive impairment. Our data provide additional evidence that deep space travel poses a real and unique threat to the integrity of neural circuits in the brain. PMID:27721383

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

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    Ostrow J

    2010-03-01

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

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

    Science.gov (United States)

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

    2016-09-01

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

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

    Science.gov (United States)

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

    2016-08-01

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

  7. Combining serum cystatin C with total bilirubin improves short-term mortality prediction in patients with HBV-related acute-on-chronic liver failure.

    Directory of Open Access Journals (Sweden)

    Zhihong Wan

    Full Text Available BACKGROUND & AIMS: HBV-related acute-on-chronic liver failure (HBV-ACLF is a severe liver disease which results in a high mortality in China. To early predict the prognosis of the patients may prevent the complications and improve the survival. This study was aimed to develop a new prognostic index to estimate the survival related to HBV-ACLF. METHODS: Consecutive patients with HBV-ACLF were included in a prospective observational study. Serum Cystatin C concentrations were measured by using the particle-enhanced immunonephelometry assay. All of the patients were followed for at least 3 months. Cox regression analysis was carried out to identify which factors were predictive of mortality. The area under the receiver operating characteristic curve (AUC was used to evaluate the efficacy of the variates for early predicting mortality. RESULTS: Seventy-two patients with HBV-ACLF were recruited between January 2012 and January 2013. Thirty patients died (41.7% during 3-months followed up. Cox multivariate regression analysis identified serum cystatin C (CysC and total bilirubin (TBil were independent factors significantly (P < 0.01 associated with survival. Our results further showed that new prognostic index (PI combining serum CysC with TBil was a good indicator for predicting the mortality of patients with HBV-ACLF. Specifically, the PI had a higher accuracy than the CTP, MELD, or MELD-Na scoring for early prediction short-term survival of HBV-ACLF patients with normal levels of serum creatinine (Cr. The survival rate in low risk group (PI < 3.91 was 94.3%, which was markedly higher than those in the high-risk group (PI ≥ 3.91 (17.4%, P < 0.001. CONCLUSION: We developed a new prognostic index combining serum CysC with TBil which early predicted the short-term mortality of HBV-ACLF patients.

  8. Vascular contributions to cognitive impairment

    Science.gov (United States)

    Flores, Alan

    2015-01-01

    Summary Unlike many neurodegenerative causes of cognitive impairment and dementia, vascular damage is preventable. Despite the heterogeneity of vascular cognitive impairment (VCI) and the complexity of its clinical presentations, the potential for limiting progression and changing the trajectory of damage makes it all the more important for physicians to be educated about the syndrome and to remain vigilant when taking care of patients. In this review, we outline an approach to patients with possible VCI, summarize current treatment and prevention guidelines, and provide an overview with case examples. PMID:26124978

  9. ESTIMATED RATE OF FATAL AUTOMOBILE ACCIDENTS ATTRIBUTABLE TO ACUTE SOLVENT EXPOSURE AT LOW INHALED CONCENTRATIONS

    Science.gov (United States)

    Acute solvent exposures may contribute to automobile accidents because they increase reaction time and decrease attention, in addition to impairing other behaviors. These effects resemble those of ethanol consumption, both with respect to behavioral effects and neurological mecha...

  10. FETAL DEXAMETHASONE EXPOSURE ACCELERATES DEVELOPMENT OF RENAL FUNCTION: RELATIONSHIP TO DOSE, CELL DIFFERENTIATION AND GROWTH INHIBITION

    Science.gov (United States)

    Fetal exposure to high doses of glucocorticoids slows cellular development and impairs organ performance, in association with growth retardation. evertheless, low doses of glucocorticoids may enhance cell differentiation and accelerate specific functions. he current study examine...

  11. NEUROSENSORY EFFECTS OF CHRONIC HUMAN EXPOSURE TO ARSENIC ASSOCIATED WITH BODY BURDEN AND ENVIRONMENTAL MEASURES

    Science.gov (United States)

    Exposure to arsenic in drinking water is known to produce a variety of health problems including peripheral neuropathy. Auditory, visual and somatosensory impairments have been reported in Mongolian farmers living in the Yellow River Valley where drinking water is contami...

  12. Severe adverse effects related to dermal exposure to a glyphosate-surfactant herbicide

    DEFF Research Database (Denmark)

    Mariager, T P; Madsen, P V; Ebbehøj, N E;

    2013-01-01

    This is a case of severe chemical burns following prolonged accidental exposure to a glyphosate-surfactant herbicide. The patient developed local swelling, bullae and exuding wounds. Neurological impairment followed affecting finger flexion and sensation with reduced nerve conduction. Imaging...

  13. Cognitive impairment and mortality among nonagenarians

    DEFF Research Database (Denmark)

    Andersen, Kjeld; Nybo, Hanne; Gaist, David;

    2002-01-01

    Cognitive impairment has been associated with increased mortality. Most studies, however, have only included small numbers, if at all, of the very old. In a large nationwide survey of all Danes born in 1905 and still alive in 1998, where the baseline examination was conducted, we examined...... interval) of 1.24 (1.00-1.55) for mildly impaired and 1.73 (1.37-2.20) for severely impaired Danes compared to individuals with no impairment. Cognitive impairment predicts mortality among the very old, even after controlling for most known predictors of mortality....... the impact of cognitive impairment on mortality over a 2-year period. No cognitive impairment was defined as a score of 24-30 points on the Mini Mental State Examination, mild cognitive impairment was defined as a score of 18-23 points, and severe impairment was defined as a score of 0-17 points. Cox...

  14. Language Impairment in Autistic Children.

    Science.gov (United States)

    Deaton, Ann Virginia

    Discussed is the language impairment of children with infantile autism. The speech patterns of autistic children, including echolalia, pronomial reversal, silent language, and voice imitation, are described. The clinical picture of the autistic child is compared to that of children with such other disorders as deafness, retardation, and…

  15. Cognitive Impairment in Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Farnaz Etesam

    2014-01-01

    Full Text Available Cognitive impairment can emerge in the earliest phases of multiple sclerosis. It strongly impacts different aspects of Multiple Sclerosis (MS patients' lives, like employment, social relationships and the overall quality of life; thus, its on-time recognition and treatment is mandatory. This paper discusses issues, diagnostic methods and treatment options for cognitive dysfunctions in MS. This paper is a descriptive review of the related studies in the recent 10 years, performing a keyword search in the main databases4T. Cognitive impairment mostly involves aspects of information processing, memory and executive functioning in MS. Neuropsychological tests like MACFIMS and BRB-N are recommended for its assessment. Still, there is no fully efficient treatment for cognitive impairment. Researchers have shown some positive effects, using disease-modifying therapies and cognitive rehabilitation. Depression, pain, fatigue and other factors influencing cognitive functions must be paid attention to4T. Recognizing cognitive impairment as a major symptom for MS, makes studying this subject one of the priorities in dealing with the disease. Therefore, a consecutive research for identification and management of this part of quality of life in MS patients is obligatory4T.4T

  16. Electrophysiology in visually impaired children

    NARCIS (Netherlands)

    Genderen, Maria Michielde van

    2006-01-01

    Inherited retinal disorders and posterior visual pathway abnormalities are important causes of visual impairment in children. Visual electrophysiology often is indispensable in diagnosing these conditions. This thesis shows the wide range of use of pediatric electro-ophthalmology, and demonstrates i

  17. Oceanography for the Visually Impaired

    Science.gov (United States)

    Fraser, Kate

    2008-01-01

    Amy Bower is a physical oceanographer and senior scientist at the Woods Hole Oceanographic Institution (WHOI) in Woods Hole, Massachusetts--she has also been legally blind for 14 years. Through her partnership with the Perkins School for the Blind in Watertown, Massachusetts, the oldest K-12 school for the visually impaired in the United States,…

  18. Language Impairment in Cerebellar Ataxia

    NARCIS (Netherlands)

    van Gaalen, Judith; de Swart, Bert J. M.; Oostveen, Judith; Knuijt, Simone; van de Warrenburg, Bart P. C.; Kremer, Berry (H. ) P. H.

    2014-01-01

    Background: Several studies have suggested that language impairment can be observed in patients with cerebellar pathology. The aim of this study was to investigate language performance in patients with spinocerebellar ataxia type 6 (SCA6). Methods: We assessed speech and language in 29 SCA6 patients

  19. Levothyroxine rescues the lead-induced hypothyroidism and impairment of long-term potentiation in hippocampal CA1 region of the developmental rats

    International Nuclear Information System (INIS)

    Lead (Pb) exposure during development has been associated with impaired long-term potentiation (LTP). Hypothyroidism happening upon subjects with occupational exposure to Pb is suggestive of an adverse effect of Pb on thyroid homeostasis, leading to the hypothesis that Pb exposure may alter thyroid hormone homeostasis. Hippocampus is one of the targets of Pb exposure, and is sensitive to and dependent on thyroid hormones, leading us to explore whether levothyroxine (L-T4) administration could alter the thyroid disequilibrium and impairment of LTP in rat hippocampus caused by Pb exposure. Our results show that Pb exposure caused a decrease in triiodothyronine (T3) and tetraiodothyronine (T4) levels accompanied by a dramatic decrease of TSH and application of L-T4 restored these changes to about control levels. Hippocampal and blood Pb concentration were significantly reduced following L-T4 treatment. L-T4 treatment rescued the impairment of LTP induced by the Pb exposure. These results suggest that Pb exposure may lead to thyroid dysfunction and induce hypothyroidism and provide a direct electrophysiological proof that L-T4 relieves chronic Pb exposure-induced impairment of synaptic plasticity. - Highlights: → Lead may interfere with thyroid hormone homeostasis and induce hypothyroidism. → Levothyroxine decreases the hippocampal and blood Pb concentration. → Levothyroxine amends the T3, T4 and TSH levels in blood. → Levothyroxine rescues the impaired LTP in CA1.

  20. Prenatal Exposure to Organophosphate Pesticides and Reciprocal Social Behavior in Childhood

    OpenAIRE

    Furlong, Melissa A.; Engel, Stephanie M.; Barr, Dana Boyd; Wolff, Mary S.

    2014-01-01

    Prenatal exposure to organophosphate pesticides (OPs) has been associated with adverse neurodevelopmental outcomes in childhood, including low IQ, Pervasive Developmental Disorder (PDD), attention problems and ADHD. Many of these disorders involve impairments in social functioning. Thus, we investigated the relationship between biomarkers of prenatal OP exposure and impaired reciprocal social behavior in childhood, as measured by the Social Responsiveness Scale (SRS). Using a multi-ethnic urb...

  1. The Relationship between Prenatal PCB Exposure and Intelligence (IQ) in 9-Year-Old Children

    OpenAIRE

    Stewart, Paul W.; Lonky, Edward; Reihman, Jacqueline; Pagano, James; Gump, Brooks B.; Darvill, Thomas

    2008-01-01

    Background Several epidemiologic studies have demonstrated relationships between prenatal exposure to polychlorinated biphenyls (PCBs) and modest cognitive impairments in infancy and early childhood. However, few studies have followed cohorts of exposed children long enough to examine the possible impact of prenatal PCB exposure on psychometric intelligence in later childhood. Of the few studies that have done so, one in the Great Lakes region of the United States reported impaired IQ in chil...

  2. The relationship between transcutaneous bilirubin changes after surgery and the prognosis in biliary atresia%测定胆道闭锁术后皮肤胆红素动态变化与预后的关系

    Institute of Scientific and Technical Information of China (English)

    王文晓; 李龙; 张金山; 刘树立; 谢华伟; 明安晓; 崔龙; 周峻

    2011-01-01

    Objective To study the relationship between the post-op transcutaneous bilirubin changes after Surgery and the prognosis in children with biliary atresia. Methods Between July 2009to December 2009,52 children( 19 males and 33 female, age: 36 d~304 d, the mean age 83d, including 5cholestasis and 47 biliary atresia)with jaundice and 59 non-jaundiced children's (28 males and 31 females,aged 26 d~200 d and the mean age 119 d) were recruited for the study. The transcutaneous bilirubin and total serum bilirubin of children with jaundice and non-jaundice were measured at the same time. Twenty-three children with biliary atresia (8 males and 15 females, aged 36 d~ 127 d and the mean age 63 d) underwent Kasai operation. The children were divided into good or poor prognosis groups according to the serum bilirubin levels of 20 μmol/L three months after operation. Measurements were compared between the two groups during hospital stay. Results Linear regression oftranscutaneous bilirubin (x) correlated with that of serum bilirubin (y) (y = 0. 945x - 46. 273, P<0. 05). The 95% confidence interval of transcutaneous bilirubin in normal children was 33. 14~96. 14μmol/L. The transcutaneous bilirubin of children with good prognosis was significantly lower than that of children with poor prognosis on postoperative day 11 ( 159 μmol/L vs 205 μmol/L,P<0. 05) and 12(151 μmol/L vs 210μmol/L,P<0. 05). Postoperative average daily decline of transcutaneous bilirubin in children with good prognosis was faster (5. 04 μmol/L vs 2. 33 μmol/L, P<0. 05). Conclusions Transcutaneous bilirubin measurement is a safe and reliable method of monitoring the decline of jaundice of children with biliary atresia.%目的 初步探讨胆道闭锁患儿术后测定皮肤胆红素动态变化与黄疸消退及预后的关系.方法 2009年7月至12月,收治黄疸患儿52例,男19例,女33例,年龄36 d~304 d,平均年龄83 d,包括胆汁淤积5例,胆道闭锁47例,采血测血清胆

  3. Application value of umbilical cord blood bilirubin levels in predicting neonatal jaundice%脐血胆红素水平在预测新生儿黄疸中的应用价值

    Institute of Scientific and Technical Information of China (English)

    李莎

    2015-01-01

    目的:探讨脐血胆红素水平在预测新生儿黄疸中的应用价值。方法选取2013年1月-2015年1月医院足月新生儿132例。于出生时、出生后24、48、72h 测定脐血胆红素水平,并按浓度分为﹤30μmol/L、≥30μmol/L、≥36μmol/L、≥42μmol/L 4组。所有新生儿均于出生时、生后24、48、72h测定经皮胆红素(测定新生儿前额及前胸2个部位,读数取平均值后记录),比较高胆红素症与非高胆红素血症组的脐血胆红素水平及不同脐血胆红素水平组高胆红素症发生率。结果新生儿脐血胆红素﹤30μmol/L组黄疸发生率为16.7%明显低于≥30μmol/L组的34.2%、≥36μmol/L组的73.3%及≥45μmol/L组的85.0%,比较差异均有统计学意义( P﹤0.05)。非高胆红素组脐血胆红素、出生后24、48、72h经皮胆红素指数均低于高胆红素组,比较差异均有统计学意义( P﹤0.05)。结论高胆红素血症新生儿的脐血胆红素相应升高,测定脐血胆红素对预测新生儿黄疸有实际的应用价值。%Objective To eXplore the application Value of umbilical cord blood bilirubin leVels in predicting neonatal jaundice. Methods Select 132 cases of term newborns. The leVel of cord blood bilirubin was measured at birth,and at 24 hours,48 hours and 72 hours after birth,according to the concentration diVided into( ﹤30μmol/L)group,(≥30μmol/L) group,(≥36μmol/L)group and(≥42μmol/L)group. The leVel of transcutaneous bilirubinometer was also measured( De-termination of the forehead and chest in two parts,taking the aVerage Value)at birth,and at 24 hours,48 hours and 72 hours after birth. comparison high bilirubin group and non hyperbilirubinemia group cord blood bilirubin leVel,and the incidence of high bilirubin in different leVels of serum bilirubin. Results Neonatal umbilical cord blood bilirubin﹤30μmol/L jaundice in-cidence was 16. 7%μmol/L group was obViously lower acuity 30

  4. Chronic Stress During Adolescence Impairs and Improves Learning and Memory in Adulthood

    OpenAIRE

    Lauren Evelyn Chaby; Cavigelli, Sonia A; Kendall Mackensie Warg; Braithwaite, Victoria A.

    2015-01-01

    HIGHLIGHTS This study tested the effects of adolescent-stress on adult learning and memory. Adolescent-stressed rats had enhanced reversal learning compared to unstressed rats. Adolescent-stress exposure made working memory more vulnerable to disturbance. Adolescent-stress did not affect adult associative learning or reference memory. Exposure to acute stress can cause a myriad of cognitive impairments, but whether negative experiences continue to hinder individual as they ag...

  5. Cognitive impairments in cerebrovascular disease

    Directory of Open Access Journals (Sweden)

    A. Yu. Emelin

    2014-01-01

    Full Text Available Cerebrovascular diseases belong to a group of the major causes of cognitive impairments, in the elderly in particular. The paper presents current ideas on the etiology and pathogenesis of vascular cognitive impairments (VCI. The etiological factors of VCI may be divided into genetic, sociodemographic, and common risk factors for vascular and other diseases. The pathogenesis of VCI is multifactorial; cognitive function decrement results from brain damage due to cerebral circulatory disorders. Damage to the deep white matter portions and basal ganglions plays a leading role in the development of cognitive deficit in cerebral circulatory insufficiency, disrupting the connections between the frontal lobes and subcortical structures (a dissociation phenomenon. Regulatory functions are impaired; instability of volitional attention develops; the speed of thinking processes and the performance of professional and everyday skills are suffered, mnestic functions being impaired to a lesser extent. Impairments in other higher cortical functions, such as speech, gnosis, praxis, thinking, generally occur in the later stages of cognitive deficit. The comprehensive approach to examining patients with cognitive dysfunctions, which encompasses physical examination with a mandatory evaluation of neurological symptoms, neuropsychological testing, laboratory studies, instrumental diagnostic methods, and structural and functional neuroimaging techniques, are most justified now. VCI therapy is a challenging task requiring the specific features of different types of cognitive deficit to be analyzed, by providing a rationale for the choice of medications. Therapeutic effectiveness may be enhanced by rational combined multimodal therapy, by keeping in mind a variety of factors for the pathogenesis of VCI.

  6. Cognitive impairments may mimic delusions.

    Science.gov (United States)

    Eterović, Marija; Kozarić-Kovačić, Dragica

    2015-12-01

    Delusions are often recognized as key to the concept of psychosis. What is delusion is one of the basic questions of psychopathology. The common denominator of definitions of delusions is the divergence between the strong conviction in the delusional belief and superior evidences to the contrary which are continually ignored. An implicit, sustainably unspoken assumption is that the person with delusional belief has cognitive capacities to process the (counter-)arguments relevant to their delusion. However, individual's cognitive capacities are not being emphasized when delusions are evaluated. Moreover, the impact of cognitive decline on formation of delusions is neglected, both in theory and practice. We elaborate that cognitive deficits may facilitate, oppose, or mimic delusions. We focus on the last, which can lead to diagnosing as delusion what could be explained by cognitive decline and better called pseudo-delusion. The risk is significant when cognition is impaired, as in demented people; an issue which has not yet been debated. True delusions are incompatible with person's cognitive capacities, i.e., if we take into account person's cognitive status, we still cannot understand how the person holds the strange belief with an extraordinary conviction. Pseudo-delusions would be beliefs, thoughts or judgments that at first seem delusional (they are false, subculturally atypical beliefs that are strongly maintained in the face of counterargument), but lose the essence of delusions after we take cognitive impairment into account. Pseudo-delusions could actually be explained or understood by person's cognitive impairments, they "fit into" them. The reported reality-based contents of delusions in the elderly, poor response to antipsychotics and lack of association with early or family history of psychiatric disorders could in part be accounted for by the bias of misdiagnosing the cognitive impairment as the delusion. Not recognizing that the cognitive impairment

  7. Chlorine gas exposure increases susceptibility to invasive lung fungal infection

    OpenAIRE

    Gessner, Melissa A.; Doran, Stephen F.; Yu, Zhihong; Dunaway, Chad W.; Matalon, Sadis; Steele, Chad

    2013-01-01

    Chlorine (Cl2) is a highly irritating and reactive gas with potential occupational and environmental hazards. Acute exposure to Cl2 induces severe epithelial damage, airway hyperreactivity, impaired alveolar fluid clearance, and pulmonary edema in the presence of heightened inflammation and significant neutrophil accumulation in the lungs. Herein, we investigated whether Cl2 exposure affected the lung antimicrobial immune response leading to increased susceptibility to opportunistic infection...

  8. 血清胆红素与尿酸检验在冠心病患者诊断中的价值分析%Value of Serum Bilirubin and Uric Acid Test in the Diagnosis of Patients With Coronary Heart Disease

    Institute of Scientific and Technical Information of China (English)

    代劲

    2015-01-01

    Objective Analysis of serum bilirubin and uric acid value to the diagnosis of coronary heart disease.MethodsSelect 80 cases of coronary heart disease patients as observation group,in the same period 80 cases of healthy subjects as control group,serum bilirubin and uric acid in test,compare test results.Results Observation group serum bilirubin level is lower than the control group,uric acid level is higher than that of control group(P<0.05); Observation group of total bilirubin,combination of bilirubin,the bilirubin decreased as the Gensini score,uric acid wil increase (P<0.05). Conclusion Inspection of serum bilirubin and uric acid levels to provide a strong basis for the diagnosis and treatment of coronary heart disease.%目的:分析血清胆红素与尿酸对冠心病的诊断价值。方法选取80例冠心病患者为观察组,同期80例健康者为对照组,均行血清胆红素和尿酸检验,比较检测结果。结果观察组血清胆红素水平低于对照组,尿酸水平则高于对照组(P<0.05);观察组总胆红素、结合胆红素、非结合胆红素随着Gensini积分的增加而减少,尿酸则会增加(P<0.05)。结论检验血清胆红素和尿酸水平可为诊疗冠心病提供有力依据。

  9. Impaired glycemia increases disease progression in mild cognitive impairment

    OpenAIRE

    Morris, Jill K.; Vidoni, Eric D.; Honea, Robyn A.; Burns, Jeffrey M.

    2013-01-01

    Insulin resistance and Type 2 Diabetes are associated with cognitive decline and increased risk for Alzheimer’s disease (AD). Relatively few studies have assessed the impact of metabolic dysfunction on conversion to AD in mild cognitive impairment (MCI), and it is unclear whether glycemic status is associated with clinically-relevant measures of cognitive decline and brain structure in MCI. This study used the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database to examine the relation...

  10. Colour Vision Impairment in Young Alcohol Consumers.

    Directory of Open Access Journals (Sweden)

    Alódia Brasil

    Full Text Ava