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Sample records for acute bilirubin encephalopathy

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

    PubMed

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

    2016-05-01

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

  2. [Pathogenesis of acute encephalitis and acute encephalopathy].

    PubMed

    Shiomi, Masashi

    2011-03-01

    Many aspects of the pathogenesis of acute encephalitis and acute encephalopathy have been clarified in this decade, although many unknown mechanisms remain to be elucidated. According to progress of MRI and neuroimmunological analysis and the observation of clinical findings, many new syndromes were found, which enhanced our understanding of acute encephalitis and acute encephalopathy. The pathogenesis of encephalitis is divided into infection and immune mediated mechanisms. The antibodies to neuronal surface antigens(NSA) such as NMDA receptors, leucin-rich glioma inactivated 1 (LGI1) and aquaporin 4 were demonstrated in specific encephalitis, limbic encephalitis and neuromyelitis optica. Anti-NSA antibody encephalitis should be treated by immunotherapy such as corticosteroid and plasmapheresis. Acute encephalitis with refractory repetitive partial seizures (AERRPS) is a devastating postinfectious disease in children and adults, although the pathogenesis of AERRPS is poorly understood. Influenza associated encephalopathy(IAE) is characterized by it's high incidence in Japanese children between 1 year and 5 years of age, its onset in the first or the second day of illness and its high mortality (15-30%) and morbidity (25-40%). We proposed the classification of IAE with poor prognosis from the neuroradiological findings. Four types of encephalopathy seem to be differentiated from each other, acute necrotizing encephalopathy (ANE) type, hemorrhagic shock and encephalopathy syndrome (HSES) type, acute brain swelling (ABS) type, febrile convulsive status epilepticus (FCSE) type. The notable radiological features are thalamic lesions in ANE, diffuse cerebral cortical cytotoxic edema in HSES, reversible cerebral swelling in ABS which sometimes reaches lethal brain herniation, and in FCSE type, dendritic high signal in subcortical white matter by DWI ("bright tree appearance") appears simultaneously with the later onset of repetitive focal seizure. These four types are

  3. Uncommon cause of acute encephalopathy in liver cirrhosis.

    PubMed

    Dieuvil, Monique; Malaty, John

    2016-01-01

    A 49-year-old woman with a medical history of alcoholic cirrhosis status post-transjugular intrahepatic portosystemic shunt (post-TIPS) in 2012, and ongoing alcohol abuse, presented to the hospital, with haematuria. CT intravenous pyelogram (IVP) was normal except for 'a large intrahepatic cystic mass adjacent to the TIPS, causing intrahepatic biliary duct dilation'. The patient also presented with acute encephalopathy, jaundice, right upper quadrant abdominal pain and hyperbilirubinaemia (total bilirubin of 8.1 mg/dL with direct bilirubin of 3.0 mg/dL). She remained encephalopathic despite adequate treatment for alcohol withdrawal, hepatic encephalopathy and enterococcus urinary tract infection. MRI of the abdomen later confirmed presence of an obstructing biloma. The biloma, drained by CT-guided percutaneous drains, demonstrated an Escherichia coli and ESBL Klebsiella infection. The patient's encephalopathy completely resolved after treatment of the infected biloma. With adequate drainage, her hyperbilirubinaemia resolved to her post-TIPS baseline (total bilirubin of 3.7 mg/dL with direct bilirubin of 3.3 mg/dL). PMID:27194673

  4. Transport and Metabolism at Blood–Brain Interfaces and in Neural Cells: Relevance to Bilirubin-Induced Encephalopathy

    PubMed Central

    Gazzin, Silvia; Strazielle, Nathalie; Tiribelli, Claudio; Ghersi-Egea, Jean-François

    2012-01-01

    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 (BBIs) into the brain, where it accumulates and exerts neurotoxic effects. In this classical view of bilirubin neurotoxicity, BBIs 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 BBIs 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–cerebrospinal fluid barriers may modulate bilirubin flux across both cellular interfaces, and that these protective functions can be affected in chronic unconjugated hyperbilirubinemia. Then the in vivo and in vitro arguments in favor of the physiological antioxidant function of intracerebral bilirubin are presented, as well as the potential role of transporters such as ABCC1 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. PMID:22629246

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  7. Determining Prevalence of Acute Bilirubin Encephalopathy in Developing Countries

    ClinicalTrials.gov

    2015-11-11

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

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

    PubMed

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

    2016-05-01

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

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

    PubMed Central

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

    2015-01-01

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

  10. Hepatic encephalopathy in acute-on-chronic liver failure.

    PubMed

    Lee, Guan-Huei

    2015-10-01

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

  11. Hemorrhagic Encephalopathy From Acute Baking Soda Ingestion.

    PubMed

    Hughes, Adrienne; Brown, Alisha; Valento, Matthew

    2016-09-01

    Baking soda is a readily available household product composed of sodium bicarbonate. It can be used as a home remedy to treat dyspepsia. If used in excessive amounts, baking soda has the potential to cause a variety of serious metabolic abnormalities. We believe this is the first reported case of hemorrhagic encephalopathy induced by baking soda ingestion. Healthcare providers should be aware of the dangers of baking soda misuse and the associated adverse effects. PMID:27625729

  12. Hemorrhagic Encephalopathy From Acute Baking Soda Ingestion

    PubMed Central

    Hughes, Adrienne; Brown, Alisha; Valento, Matthew

    2016-01-01

    Baking soda is a readily available household product composed of sodium bicarbonate. It can be used as a home remedy to treat dyspepsia. If used in excessive amounts, baking soda has the potential to cause a variety of serious metabolic abnormalities. We believe this is the first reported case of hemorrhagic encephalopathy induced by baking soda ingestion. Healthcare providers should be aware of the dangers of baking soda misuse and the associated adverse effects. PMID:27625729

  13. Hemorrhagic Encephalopathy From Acute Baking Soda Ingestion.

    PubMed

    Hughes, Adrienne; Brown, Alisha; Valento, Matthew

    2016-09-01

    Baking soda is a readily available household product composed of sodium bicarbonate. It can be used as a home remedy to treat dyspepsia. If used in excessive amounts, baking soda has the potential to cause a variety of serious metabolic abnormalities. We believe this is the first reported case of hemorrhagic encephalopathy induced by baking soda ingestion. Healthcare providers should be aware of the dangers of baking soda misuse and the associated adverse effects.

  14. Hemorrhagic Encephalopathy From Acute Baking Soda Ingestion

    PubMed Central

    Hughes, Adrienne; Brown, Alisha; Valento, Matthew

    2016-01-01

    Baking soda is a readily available household product composed of sodium bicarbonate. It can be used as a home remedy to treat dyspepsia. If used in excessive amounts, baking soda has the potential to cause a variety of serious metabolic abnormalities. We believe this is the first reported case of hemorrhagic encephalopathy induced by baking soda ingestion. Healthcare providers should be aware of the dangers of baking soda misuse and the associated adverse effects.

  15. Acute encephalopathy and tubulointerstitial nephritis associated with Yersinia pseudotuberculosis.

    PubMed

    Kaito, Hiroshi; Kamei, Koichi; Ogura, Masao; Kikuchi, Eriko; Hoshino, Hideki; Nakagawa, Satoshi; Matsuoka, Kentaro; Abe, Jun; Ito, Shuichi

    2012-12-01

    We report the case of a 28-month-old boy with encephalopathy and acute tubulointerstitial nephritis possibly associated with Yersinia pseudotuberculosis (Yp) infection. He was transferred to our center because of impairment of renal function and altered consciousness. He had fever for 5 days after recurrent vomiting and diarrhea. Computed tomography scan was normal, but electroencephalogram (EEG) analyses showed generalized slow wave patterns. Continuous hemodialysis was undergone and then his renal function was improved, but altered consciousness persisted. Single photon emission computed tomography (SPECT) revealed abnormally low signals at entire field, which suggested that he was suffered from encephalopathy. Phenobarbital administration and post-encephalopathy rehabilitation were started, and he recovered in fully premorbid state with normal EEG and SPECT findings on the 33rd hospital day. Various bacterial cultures were negative, but both Yp antibody and Yp-derived mitogen (YPM) antibody, the antibody of a specific Yp exotoxin, had an extremely high titer. This is the first report of encephalopathy potentially caused by Yp, indicated by the presence of a high Yp and YPM antibody titer.

  16. Acute febrile encephalopathy in adults from Northwest India

    PubMed Central

    Bhalla, Ashish; Suri, Vika; Varma, Subhash; Sharma, Navneet; Mahi, Sushil; Singh, Paramjeet; Khandelwal, Niranjan K

    2010-01-01

    Background: Acute onset fever with altered mentation is a common problem encountered by the physician practicing in tropical countries. Central nervous system (CNS) infections are the most common cause resulting in fever with altered mentation in children. Aim: In this study, we have tried to analyze the cause of encephalopathy following short febrile illness in adults presenting to a tertiary care center in Northwestern part of India. Setting and Design: A prospective observational study carried out in a tertiary care center in the Northwestern India over a period of 1 year. Material and Methods A total of 127 patients with fever of less than 2 weeks duration along with alteration in mentation were studied prospectively over a period of 12 months. The demographic variables were recorded in detail. In addition to routine investigations, cerebrospinal fluid analysis, noncontrast- and contrast-enhanced computed tomography, along with magnetic resonance imaging were performed in all the subjects. Statistical Analysis The results were analyzed using SPSS statistical software. The values were expressed as mean with standard deviation for contiguous variable as percentage for the others. Results and Conclusion Out of these, 70% had primary CNS infection as the etiology. A total of 33% patients had meningitis, 29.9% had evidence of meningoencephalitis, and 12.7% were diagnosed as sepsis-associated encephalopathy. These were followed by cerebral malaria, leptospirosis, and brain abscess as the cause of febrile encephalopathy in adults. Among the noninfectious causes, acute disseminated encephalomyelitis, cortical venous thrombosis, and neuroleptic malignant syndrome were documented in 2.36% each. In 11% of the patients, the final diagnosis could not be made in spite of the extensive investigations. Our study demonstrates that acute febrile encephalopathy in adults is a heterogeneous syndrome with primary CNS infections being the commonest etiology. PMID:20930964

  17. Acute Liver Failure and Hepatic Encephalopathy After Cleft Palate Repair.

    PubMed

    Kocaaslan, Nihal Durmuş; Tuncer, Fatma Betul; Tutar, Engin; Celebiler, Ozhan

    2015-09-01

    Paracetamol is the most commonly used analgesic after cleft palate repair. It has rarely caused acute hepatic failure at therapeutic or supratherapeutic doses. Only one case of therapeutic paracetamol toxicity after cleft palate repair had been reported previously. Here, we present a similar patient who developed acute liver failure and hepatic encephalopathy after an uncomplicated cleft palate surgery. Lack of large prospective trials in young children due to ethical concerns increases the value of the case reports of acetaminophen toxicity at therapeutic doses. The dosing recommendations of paracetamol may need to be reconsidered after cleft palate surgery.

  18. Acute encephalopathy of Bacillus cereus mimicking Reye syndrome.

    PubMed

    Ichikawa, Kazushi; Gakumazawa, Masayasu; Inaba, Aya; Shiga, Kentaro; Takeshita, Saoko; Mori, Masaaki; Kikuchi, Nobuyuki

    2010-09-01

    We present an 11-year-old boy diagnosed as having acute encephalopathy and liver failure with the underlying condition of a metabolic dysfunction. He developed convulsions and severe consciousness disturbance following gastroenteritis after the ingestion of some fried rice. He showed excessive elevation of transaminases, non-ketotic hypoglycemia and hyperammonemia, which were presumed to reflect a metabolic dysfunction of the mitochondrial beta-oxidation, and he exhibited severe brain edema throughout the 5th hospital day. He was subjected to mild hypothermia therapy for encephalopathy, and treated with high-dose methylprednisolone, cyclosporine and continuous hemodiafiltration for liver failure, systemic organ damage and hyperammonemia. The patient recovered with the sequela of just mild intelligence impairment. In this case, Bacillus cereus, producing emetic toxin cereulide, was detected in a gastric fluid specimen, a stool specimen and the fried rice. It was suggested that the cereulide had toxicity to mitochondria and induced a dysfunction of the beta-oxidation process. The patient was considered as having an acute encephalopathy mimicking Reye syndrome due to food poisoning caused by cereulide produced by B. cereus.

  19. Posterior Reversible Encephalopathy Syndrome (PRES) After Acute Pancreatitis

    PubMed Central

    Murphy, Tara; Al-Sharief, Khalid; Sethi, Vineeta; Ranger, Gurpreet S.

    2015-01-01

    Posterior reversible encephalopathy syndrome (PRES) is an unusual condition typified by acute visual impairment caused by sudden, marked parieto-occipital vasogenic edema. Thought to be inflammatory in origin, it has been described in patients undergoing chemotherapy, with autoimmune disease, and in some infections. We report a case of PRES that occurred one week after an episode of acute pancreatitis in an otherwise healthy 40-year-old female. There was progressive visual impairment over a 24-hour period with almost complete visual loss, with characteristic findings on magnetic resonance imaging. After treatment with steroids, the visual loss recovered. Clinicians should retain an index of suspicion of this rare condition in patients with visual impairment after acute pancreatitis. PMID:26759673

  20. Specific HLA genotypes confer susceptibility to acute necrotizing encephalopathy.

    PubMed

    Hoshino, A; Saitoh, M; Miyagawa, T; Kubota, M; Takanashi, J-I; Miyamoto, A; Tokunaga, K; Oka, A; Mizuguchi, M

    2016-09-01

    Acute necrotizing encephalopathy (ANE) is a rare and severe syndrome of acute encephalopathy triggered by viral infections. Cytokine storm is considered as the main pathogenetic mechanism of ANE. ANE is prevalent in East Asia, suggesting the association of host genetic factors. To elucidate the genetic background of Japanese ANE, we examined genotypes of human leukocyte antigen (HLA)-A, C, B, DRB1, DQB1 and DPB1 in 31 patients. Significant positive association was observed in both the allele frequency and positivity of DRB1*09:01 (P=0.043 and 0.025, respectively), as well as those of DQB1*03:03 (P=0.034 and 0.026, respectively). The carrier frequency of DRB1*09:01 and DQB1*03:03 alleles was higher in the patients (45.16%) than in controls (28.57%). These alleles are more common in East Asian than in European populations, and are reportedly associated with various autoimmune diseases in Japanese patients. Our data provide further evidence that altered immune response based on individual HLA genotypes may contribute to ANE pathogenesis. PMID:27467284

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

    PubMed Central

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

    2016-01-01

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

  2. Biology of Bilirubin Photoisomers.

    PubMed

    Hansen, Thor Willy Ruud

    2016-06-01

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

  3. Bilirubin - urine

    MedlinePlus

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

  4. Blood-brain barrier dysfunction in acute lead encephalopathy: a reappraisal.

    PubMed

    Bouldin, T W; Mushak, P; O'Tuama, L A; Krigman, M R

    1975-12-01

    Acute lead encephalopathy was induced in adult guinea pigs by administering daily oral doses of lead carbonate. During the development of the encephalopathy, the structural and functional integrity of the blood-brain barrier was evaluated with electron microscopy and tracer probes. Blood, cerebral gray matter, liver, and kidney were analyzed for lead, calcium, and magnesium content. The animals regularly developed an encephalopathy after four doses of lead. There were no discernible pathomorphologic alterations in the cerebral capillaries or perivascular glial sheaths. Furthermore, no evidence of blood-brain barrier dysfunction was demonstrated with Evans blue-albumin complex or horseradish peroxidase. Blood-brain barrier permeability to radiolead was not increased in the intoxicated animals. During the development of the encephalopathy there was a progressive rise in the lead concentration in all tissues. Concurrently, there was a significant rise in brain calcium. These results suggest that the encephalopathic effects of lead may be mediated directly at the neuronal level.

  5. Bilirubin Test

    MedlinePlus

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

  6. A case of life-threatening acute kidney injury with toxic encephalopathy caused by Dioscorea quinqueloba.

    PubMed

    Kang, Kyung-Sik; Heo, Sang Taek

    2015-01-01

    Some herbal medications induce acute kidney injury. The acute kidney injuries caused by herbal medications are mild and commonly treated by palliative care. A 51-years-old man who drank the juice squeezed from the raw tubers of Dioscorea quinqueloba (D. quinqueloba) was admitted with nausea, vomiting and chilling. He developed a seizure with decreased level of consciousness. He was diagnosed with acute kidney injury, which was cured by continuous venovenous hemodialfiltration. Non-detoxified D. quinqueloba can cause severe acute kidney injury with toxic encephalopathy. It is critical to inform possible adverse effects of the medicinal herbs and to implement more strict regulation of these products.

  7. Identification of Viruses in Cases of Pediatric Acute Encephalitis and Encephalopathy Using Next-Generation Sequencing.

    PubMed

    Kawada, Jun-Ichi; Okuno, Yusuke; Torii, Yuka; Okada, Ryo; Hayano, Satoshi; Ando, Shotaro; Kamiya, Yasuko; Kojima, Seiji; Ito, Yoshinori

    2016-01-01

    Acute encephalitis/encephalopathy is a severe neurological syndrome that is occasionally associated with viral infection. Comprehensive virus detection assays are desirable because viral pathogens have not been identified in many cases. We evaluated the utility of next-generation sequencing (NGS) for detecting viruses in clinical samples of encephalitis/encephalopathy patients. We first determined the sensitivity and quantitative performance of NGS by comparing the NGS-determined number of sequences of human herpesvirus-6 (HHV-6) in clinical serum samples with the HHV-6 load measured using real-time PCR. HHV-6 was measured as it occasionally causes neurologic disorders in children. The sensitivity of NGS for detection of HHV-6 sequences was equivalent to that of real-time PCR, and the number of HHV-6 reads was significantly correlated with HHV-6 load. Next, we investigated the ability of NGS to detect viral sequences in 18 pediatric patients with acute encephalitis/encephalopathy of unknown etiology. A large number of Coxsackievirus A9 and mumps viral sequences were detected in the cerebrospinal fluid of 2 and 1 patients, respectively. In addition, Torque teno virus and Pepper mild mottle viral sequences were detected in the sera of one patient each. These data indicate that NGS is useful for detection of causative viruses in patients with pediatric encephalitis/encephalopathy. PMID:27625312

  8. Identification of Viruses in Cases of Pediatric Acute Encephalitis and Encephalopathy Using Next-Generation Sequencing

    PubMed Central

    Kawada, Jun-ichi; Okuno, Yusuke; Torii, Yuka; Okada, Ryo; Hayano, Satoshi; Ando, Shotaro; Kamiya, Yasuko; Kojima, Seiji; Ito, Yoshinori

    2016-01-01

    Acute encephalitis/encephalopathy is a severe neurological syndrome that is occasionally associated with viral infection. Comprehensive virus detection assays are desirable because viral pathogens have not been identified in many cases. We evaluated the utility of next-generation sequencing (NGS) for detecting viruses in clinical samples of encephalitis/encephalopathy patients. We first determined the sensitivity and quantitative performance of NGS by comparing the NGS-determined number of sequences of human herpesvirus-6 (HHV-6) in clinical serum samples with the HHV-6 load measured using real-time PCR. HHV-6 was measured as it occasionally causes neurologic disorders in children. The sensitivity of NGS for detection of HHV-6 sequences was equivalent to that of real-time PCR, and the number of HHV-6 reads was significantly correlated with HHV-6 load. Next, we investigated the ability of NGS to detect viral sequences in 18 pediatric patients with acute encephalitis/encephalopathy of unknown etiology. A large number of Coxsackievirus A9 and mumps viral sequences were detected in the cerebrospinal fluid of 2 and 1 patients, respectively. In addition, Torque teno virus and Pepper mild mottle viral sequences were detected in the sera of one patient each. These data indicate that NGS is useful for detection of causative viruses in patients with pediatric encephalitis/encephalopathy. PMID:27625312

  9. Hepatic encephalopathy in patients with acute decompensation of cirrhosis and acute-on-chronic liver failure.

    PubMed

    Romero-Gómez, Manuel; Montagnese, Sara; Jalan, Rajiv

    2015-02-01

    Hepatic encephalopathy in a hospitalized cirrhotic patient is associated with a high mortality rate and its presence adds further to the mortality of patients with acute-on-chronic liver failure (ACLF). The exact pathophysiological mechanisms of HE in this group of patients are unclear but hyperammonemia, systemic inflammation (including sepsis, bacterial translocation, and insulin resistance) and oxidative stress, modulated by glutaminase gene alteration, remain as key factors. Moreover, alcohol misuse, hyponatremia, renal insufficiency, and microbiota are actively explored. HE diagnosis requires exclusion of other causes of neurological, metabolic and psychiatric dysfunction. Hospitalization in the ICU should be considered in every patient with overt HE, but particularly if this is associated with ACLF. Precipitating factors should be identified and treated as required. Evidence-based specific management options are limited to bowel cleansing and non-absorbable antibiotics. Ammonia lowering drugs, such as glycerol phenylbutyrate and ornithine phenylacetate show promise but are still in clinical trials. Albumin dialysis may be useful in refractory cases. Antibiotics, prebiotics, and treatment of diabetes reduce systemic inflammation. Where possible and not contraindicated, large portal-systemic shunts may be embolized but liver transplantation is the most definitive step in the management of HE in this setting. HE in patients with ACLF appears to be clinically and pathophysiologically distinct from that of acute decompensation and requires further studies and characterization.

  10. Influenza Virus-Associated Fatal Acute Necrotizing Encephalopathy: Role of Nonpermissive Viral Infection?

    PubMed Central

    Mungaomklang, Anek; Chomcheoy, Jiraruj; Wacharapluesadee, Supaporn; Joyjinda, Yutthana; Jittmittraphap, Akanitt; Rodpan, Apaporn; Ghai, Siriporn; Saraya, Abhinbhen; Hemachudha, Thiravat

    2016-01-01

    In 2014, two unusual peaks of H1N1 influenza outbreak occurred in Nakhon Ratchasima Province, in Thailand. Among 2,406 cases, one of the 22 deaths in the province included a 6-year-old boy, who initially presented with acute necrotizing encephalopathy. On the other hand, his sibling was mildly affected by the same influenza virus strain, confirmed by whole-genome sequencing, with one silent mutation. Absence of acute necrotizing encephalopathy and other neurological illnesses in the family and the whole province, with near identical whole viral genomic sequences from the two siblings, and an absence of concomitant severe lung infection (cytokine storm) at onset suggest nonpermissive infection as an alternative pathogenetic mechanism of influenza virus. PMID:27812294

  11. Distinguishing Acute Encephalopathy with Biphasic Seizures and Late Reduced Diffusion from Prolonged Febrile Seizures by Acute Phase EEG Spectrum Analysis

    PubMed Central

    Oguri, Masayoshi; Saito, Yoshiaki; Fukuda, Chisako; Kishi, Kazuko; Yokoyama, Atsushi; Lee, Sooyoung; Torisu, Hiroyuki; Toyoshima, Mitsuo; Sejima, Hitoshi; Kaji, Shunsaku; Hamano, Shin-ichiro; Okanishi, Toru; Tomita, Yutaka; Maegaki, Yoshihiro

    2016-01-01

    Background To differentiate the features of electroencephalography (EEG) after status epileptics in febrile children with final diagnosis of either febrile seizure (FS) or acute encephalopathy for an early diagnosis. Methods We retrospectively collected data from 68 children who had status epilepticus and for whom EEGs were recorded within 120 h. These included subjects with a final diagnosis of FS (n = 20), epileptic status (ES; n = 11), acute encephalopathy with biphasic seizures and late reduced diffusion (AESD; n = 18), mild encephalopathy with a reversible splenial lesion (MERS; n = 7), other febrile encephalopathies (n = 10), hypoxic-ischemic encephalopathy (n = 1), and intracranial bleeding (n = 1). Initially, all EEGs were visually assessed and graded, and correlation with outcome was explored. Representative EEG epochs were then selected for quantitative analyses. Furthermore, data from AESD (n = 7) and FS (n = 16) patients for whom EEG was recorded within 24 h were also compared. Results Although milder and most severe grades of EEG correlated with neurological outcome, the outcome of moderate EEG severity group was variable and was not predictable from usual inspection. Frequency band analysis revealed that solid delta power was not significantly different among the five groups (AESD, MERS, FS, ES and control), and that MERS group showed the highest theta band power. The ratios of delta/alpha and (delta + theta)/(alpha + beta) band powers were significantly higher in the AESD group than in other groups. The alpha and beta band powers in EEGs within 24 h from onset were significantly lower in the AESD group. The band powers and their ratios showed earlier improvement towards 24 h in FS than in AESD. Conclusion Sequential EEG recording up to 24 h from onset appeared to be helpful for distinction of AESD from FS before emergence of the second phase of AESD. PMID:27046946

  12. Bilirubin - blood

    MedlinePlus

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

  13. [Acute encephalopathy due to late-onset maple syrup urine disease in a school boy].

    PubMed

    Qu, Su-Qing; Yang, Li-Cai; Luan, Zuo; Du, Kan; Yang, Hui

    2012-03-01

    Maple syrup urine disease is a common amino acids metabolic disease. In most patients, onset occurs in the neonatal period and infancy. In this study, the case of a school boy with acute encephalopathy due to late-onset maple syrup urine disease is summarized. The boy (8.5 years) was admitted because of acute encephalopathy after suffering from infection for two days at the age of eight and a half years. Metabolic acidosis, hyperuricemia and decreased protein level in cerebrospinal fluid were found by general laboratory tests. Magnetic resonance imaging of the brain revealed signal intensity abnormalities in the bilateral cerebellum dentate nucleus, brainstem, thalamus, putamen, caudate nucleus and cortex of the cerebral hemispheres. On T1WI and T2WI scanning, hyperintensive signal was found. Blood leucine and valine were significantly elevated. Urinary 2-hydroxy isovaleric acid, 3-hydroxybutyric acid, 2-keto isovaleric acid, and 2-keto acid also increased. Both the blood amino acid and urine organic acid profiles led to the diagnosis of maple syrup urine disease. In the acute period, the patient was treated with a large dose of vitamin B1, glucose, L-carnitine and a protein-restrict diet. The patient's condition improved significantly after five days of treatment, and he recovered completely two days later. Afterwards, treatment with vitamin B1, L-carnitine and a protein-restrict diet (1 g/kg/day) was continued. One and a half months later, blood amino acids and urine organic acids returned to normal. Magnetic resonance imaging of the brain also indicated a great improvement. It was concluded that inborn metabolic disease should be considered in the patients with an onset similar to acute encephalopathy. Early diagnosis and proper treatment can prevent brain damage and improve prognosis.

  14. Acute multiple focal neuropathies and delayed postanoxic encephalopathy after alcohol intoxication

    PubMed Central

    Wang, Wei-Che; Yang, Hsiu-Chun; Chen, Yao-Jen

    2015-01-01

    Acute-onset alcohol-associated neuropathy is only occasionally reported, and delayed postanoxic encephalopathy is rare. Here, we report a male who developed acute multiple focal neuropathies and later delayed postanoxic encephalopathy after alcohol intoxication. He had hypoxia and rhabdomyolysis, presenting with acute renal failure initially, and cardiopulmonary support, including mechanical ventilation, led to improvement of the patient at the acute stage. He suffered from bilateral hand numbness and mild weakness of the right lower limb thereafter. Nerve-conduction study revealed no pickup of compound muscle action potential or sensory nerve action potential in the bilateral ulnar nerve, but showed attenuated amplitude of compound muscle action potential in the right femoral nerve. Multiple focal neuropathies were suspected, and he received outpatient rehabilitation after being discharged. However, the patient developed gradual onset of weakness in four limbs and cognitive impairment 23 days after the hypoxia event. Brain computed tomography showed low attenuation over bilateral globus pallidus, and brain magnetic resonance imaging disclosed diffuse increased signal intensity on T2-weighted images and fluid-attenuated inversion recovery in bilateral white matter. He was admitted again under the impression of delayed postanoxic brain injury. Supportive treatment and active rehabilitation were given. He had gradual improvement in motor and functional status after rehabilitation. He could walk with festinating gait under supervision, and needed only minimal assistance in performing activities of daily living approximately 1 year later. PMID:26229472

  15. [Acute edematous encephalopathy presenting with refractory generalized status epilepticus: an autopsy case].

    PubMed

    Yamashita, M; Yamamoto, T; Yasuda, T

    2001-11-01

    A previously healthy, 29-year-old man developed generalized convulsion with disturbed consciousness 3 days after the flu-like symptoms. On the next day, his convulsion evolved into generalized status epilepticus (GSE) that was unresponsive to administration of various anticonvulsants. Then, intravenous anesthetic agents, including midazolam, propofol and vecuronium sodium, were continuously infused. During the following 9 days, despite of high-dose infusion of these anesthetic agents, his GSE could not be suppressed, and complex partial seizure with secondary generalization frequently occurred. The patient was comatose and mechanically ventilated, whereas the brainstem reflexes were preserved. Electroencephalogram revealed a diffuse slowing of the background activity and occasional focal spike and wave complexes with secondary generalization. Cerebrospinal fluid analysis showed pleocytosis and elevated protein concentration. Cranial CT scans obtained on day 8 demonstrated brain edema. On day 10, his GSE ceased with abolition of the brainstem reflexes, and he lapsed into brain death resulting from the progressive brain edema. Over the following six days, his systemic circulation gradually worsened, and he died on day 16. On postmortem examination, the brain was markedly edematous and showed the findings consistent with acute anoxic encephalopathy with extensive circulatory stasis. Mild gliosis was observed in the insular cortex, yet no evidence of inflammatory disease was found throughout the brain. This patient was characterized by acutely progressive severe brain edema without inflammatory changes, suggesting that his primary disease was acute toxic encephalopathy presumably induced by viral infection. His GSE was refractory and unresponsive to the intensive treatment with the intravenous anesthetic agents. This case epitomizes the difficulties in controlling refractory seizures in some patients with encephalopathy or encephalitis.

  16. Acute encephalopathy associated with ingestion of a mushroom, Pleurocybella porrigens (angel's wing), in a patient with chronic renal failure.

    PubMed

    Obara, Koji; Wada, Chizu; Yoshioka, Toshiaki; Enomoto, Katsuhiko; Yagishita, Saburo; Toyoshima, Itaru

    2008-04-01

    The authors report an autopsy case of acute encephalopathy in which generalized convulsion and coma occurred after ingestion of Pleurocybella porrigens (angel's wing mushroom). The patient was a 65-year-old man who had undergone hemodialysis for 3 months due to chronic renal failure. Pathologic examination of the brain revealed extensive postinfarction-like cystic necrosis in the bilateral putamens and multiple spotty necroses in the deep cerebral and cerebellar cortices. In 2004, similar acute encephalopathy related to ingestion of the mushroom was endemic in Japan, the pathogenesis of which remains to be elucidated.

  17. Drug-Related Hyponatremic Encephalopathy: Rapid Clinical Response Averts Life-Threatening Acute Cerebral Edema

    PubMed Central

    Siegel, Arthur J.; Forte, Sophie S.; Bhatti, Nasir A.; Gelda, Steven E.

    2016-01-01

    Patient: Female, 63 Final Diagnosis: Drug-induced hyponatremic encephalopathy Symptoms: Seizures • coma Medication: Hypertonic 3% saline infusion Clinical Procedure: — Specialty: Internal Medicine Objective: Unusual clinical course Background: Drug-induced hyponatremia characteristically presents with subtle psychomotor symptoms due to its slow onset, which permits compensatory volume adjustment to hypo-osmolality in the central nervous system. Due mainly to the syndrome of inappropriate antidiuretic hormone secretion (SIADH), this condition readily resolves following discontinuation of the responsible pharmacological agent. Here, we present an unusual case of life-threatening encephalopathy due to adverse drug-related effects, in which a rapid clinical response facilitated emergent treatment to avert life-threatening acute cerebral edema. Case Report: A 63-year-old woman with refractory depression was admitted for inpatient psychiatric care with a normal physical examination and laboratory values, including a serum sodium [Na+] of 144 mEq/L. She had a grand mal seizure and became unresponsive on the fourth day of treatment with the dual serotonin and norepinephrine reuptake inhibitor [SNRI] duloxetine while being continued on a thiazide-containing diuretic for a hypertensive disorder. Emergent infusion of intravenous hypertonic (3%) saline was initiated after determination of a serum sodium [Na+] of 103 mEq/L with a urine osmolality of 314 mOsm/kg H20 and urine [Na+] of 12 mEq/L. Correction of hyposmolality in accordance with current guidelines resulted in progressive improvement over several days, and she returned to her baseline mental status. Conclusions: Seizures with life-threatening hyponatremic encephalopathy in this case likely resulted from co-occurring SIADH and sodium depletion due to duloxetine and hydrochlorothiazide, respectively. A rapid clinical response expedited diagnosis and emergent treatment to reverse life-threatening acute cerebral edema

  18. Periodic synchronous discharge occurred in an elderly with acute valacyclovir-associated encephalopathy.

    PubMed

    Nakatani, Mitsuyoshi; Tsukino, Mitsuhiro; Takahashi, Ryosuke; Ikeda, Akio

    2016-07-28

    An 81-year-old woman suffering from sarcoidosis, chronic renal failure caused by hypertention was treated by valacyclovir 500 mg/day, for the diagnosis of herpes zoster of her right back. Her consciousness gradually became worse, and 3 days after taking the drug, she was sent to the emergency department of the hospital. Her conscious level was E2V2M5 (Glasgow Coma Scale) and myoclonus especially in her lower extremities occurred. Head CT and MRI show no obvious, acute abnormal findings other than chronic ischemic lesions, while an electroencephalogram (EEG) shows periodic synchronous discharges (PSDs) and disorganized background activity. Based on these findings, she was diagnosed as valacyclovir-associated acute encephalopathy. After conservative therapy of maintenance hemodialysis, her consciousness gradually improved, and PSDs disappeared accordingly and background activity of EEG became improved. In this case report, we presented valacyclovir-associated neurotoxicity with PSDs in EEG as potentially a surrogate marker. We should be cautious to use valaciclovir which may cause drug-induced encephalopathy especially in elderly or patients with renal failure even though the dose was adjusted in advance. PMID:27356736

  19. Acute encephalopathy with biphasic seizures and late reduced diffusion associated with hemophagocytic syndrome.

    PubMed

    Tadokoro, Rieko; Okumura, Akihisa; Nakazawa, Tomoyuki; Hara, Satoshi; Yamakawa, Yoko; Kamata, Ayako; Kinoshita, Keiji; Obinata, Kaoru; Shimizu, Toshiaki

    2010-06-01

    We reported a girl with HHV-6 infection associated with both acute encephalopathy with biphasic seizures and late reduced diffusion, and hemophagocytic syndrome. She had a prolonged convulsion after a one-day history of febrile illness. Cerebrospinal fluid or brain CT showed no abnormalities on admission and her consciousness was recovered on the next day. However, a prolonged seizure and deterioration of consciousness appeared on the sixth day of illness. Diffusion-weighted images revealed marked reduction of water diffusion in the bilateral frontal areas. HHV-6 infection was virologically proven by polymerase chain reaction. She was treated with gamma-globulin, steroid pulse therapy, and brain hypothermia. In addition, decrease in white blood cells and platelet counts, and elevation of liver enzymes and ferritin were noted on the fourth day of illness. Hemophagocytic macrophages were revealed by bone marrow aspiration on the sixth day. Her hematological and blood chemistry abnormalities recovered gradually after steroid pulse therapy. An elevation of interleukin-6, -8, and -10, and tumor necrosis factor in the serum and that of interleukin-4, -6, and-8 in the cerebrospinal fluid were observed at the onset of a late seizure. These facts suggested that hypercytokinemia will be related to the pathogenesis of acute encephalopathy of our patient. PMID:19556082

  20. Acute confusional state caused by Hashimoto's encephalopathy in a patient with hypothyroidism: a case report

    PubMed Central

    Nookala, Vinod; Srivastava, Anupam; Qazizadeh, Salim; Fischman, Daniel

    2009-01-01

    Introduction Hashimoto's Encephalopathy is an unusual condition associated with Hashimoto's Thyroiditis. This immune-mediated, steroid-dependent entity was first described thirty years ago. In this case report, we discuss the importance of considering this diagnosis in the evaluation of confusion. Case presentation The patient is a 55-year-old African-American woman residing in United States, who was admitted to the hospital with a four-day history of mental status changes. Her past medical history was significant for type II Diabetes Mellitus, Hypertension, and Hypothyroidism. There was no reported seizure activity. The patient's vital signs were stable on admission. On examination, the patient was awake, alert, oriented to place and time. Her neurological examination revealed agraphia and dyslexia. Her speech showed lack of fluency and hesitation. Her complete blood count and electrolytes were within normal limits. The patient's brain CT scan did not reveal any significant findings. Her Magnetic Resonance Imaging only revealed mild chronic microangiopathy, which caused by “small vessel disease.” Her Electroencephalogram did not reveal any finding consistent with seizure activity. Cerebral spinal fluid analysis was likewise did not reveal a cause for this patient's acute onset of confusion. In contrast to the above negative finding, this patient's Thyroid stimulating hormone was discovered to be 15 UIU/ml. She was subsequently given 1000 mg of intravenous Methylprednisolone daily for 3 days. This three-day course of high-dose, intravenous steroids resulted complete resolution of the patient's symptoms. She was then discharged on an eleven-day course of oral prednisone 60 mg. Conclusion Hashimoto's Encephalopathy should be considered in the differential diagnosis of an acute confusional state since it is responsive to steroid therapy and represents a readily reversible cause acute mental status changes. Clues to this diagnosis include elevated antithyroid

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

    PubMed

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

    2015-11-15

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

  2. Long-term survival in acute arsenic encephalopathy. Follow-up using newer measures of electrophysiologic parameters.

    PubMed

    Fincher, R M; Koerker, R M

    1987-03-01

    A 20-year-old man survived acute massive arsenic ingestion. The resultant severe encephalopathy and peripheral neuropathy showed limited long-term recovery over the following two years. The patient's clinical course was followed using visual and auditory evoked potentials, computed tomography, electroencephalography, and electromyography.

  3. The Optimal Management of Acute Febrile Encephalopathy in the Aged Patient: A Systematic Review

    PubMed Central

    Sheybani, Fereshte; Naderi, HamidReza; Sajjadi, Sareh

    2016-01-01

    The elderly comprise less than 13 percent of world population. Nonetheless, they represent nearly half of all hospitalized adults. Acute change in mental status from baseline is commonly seen among the elderly even when the main process does not involve the central nervous system. The term “geriatric syndrome” is used to capture those clinical conditions in older people that do not fit into discrete disease categories, including delirium, falls, frailty, dizziness, syncope, and urinary incontinence. Despite the growing number of elderly population, especially those who require hospitalization and the high burden of common infections accompanied by encephalopathy among them, there are several unresolved questions regarding the optimal management they deserve. The questions posed in this systematic review concern the need to rule out CNS infection in all elderly patients presented with fever and altered mental status in the routine management of febrile encephalopathy. In doing so, we sought to identify all potentially relevant articles using searches of web-based databases with no language restriction. Finally, we reviewed 93 research articles that were relevant to each part of our study. No prospective study was found to address how should AFE in the aged be optimally managed. PMID:26989409

  4. The Optimal Management of Acute Febrile Encephalopathy in the Aged Patient: A Systematic Review.

    PubMed

    Sheybani, Fereshte; Naderi, Hamid Reza; Sajjadi, Sareh

    2016-01-01

    The elderly comprise less than 13 percent of world population. Nonetheless, they represent nearly half of all hospitalized adults. Acute change in mental status from baseline is commonly seen among the elderly even when the main process does not involve the central nervous system. The term "geriatric syndrome" is used to capture those clinical conditions in older people that do not fit into discrete disease categories, including delirium, falls, frailty, dizziness, syncope, and urinary incontinence. Despite the growing number of elderly population, especially those who require hospitalization and the high burden of common infections accompanied by encephalopathy among them, there are several unresolved questions regarding the optimal management they deserve. The questions posed in this systematic review concern the need to rule out CNS infection in all elderly patients presented with fever and altered mental status in the routine management of febrile encephalopathy. In doing so, we sought to identify all potentially relevant articles using searches of web-based databases with no language restriction. Finally, we reviewed 93 research articles that were relevant to each part of our study. No prospective study was found to address how should AFE in the aged be optimally managed. PMID:26989409

  5. [Fractionated P-bilirubins].

    PubMed

    Schou, C S; Mortensen, H

    1989-08-14

    A diazo-based dry film technique for the estimation of different bilirubins in plasma is now available. This procedure separates bilirubins from icteric sera into three separate fractions: bilirubin (unconjugated), bilirubin-glucuronides (mono + diglucuronide) and bilirubin-albumin. In newborns with prolonged jaundice classification of hyperbilirubinemia is of importance for choice of treatment. While binding of bilirubin and bilirubin-glucuronides to albumin is non covalent, reversible, bilirubin-albumin appears to be firmly associated with albumin by covalent bonds. This causes delayed clearance of this bilirubin fraction from plasma as the half-life of albumin is approximately 18 days. Hence the substance concentration of bilirubin-albumin will decrease at a slower rate than will bilirubin and bilirubin-glucuronide, despite hepatobiliary recovery. Bilirubin-albumin may therefore prove of value in the differentiation between different clinical entities with hyperbilirubinemia. PMID:2773134

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

    PubMed

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

    2016-01-01

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

  7. Pathogenesis of Hepatic Encephalopathy

    PubMed Central

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

    2012-01-01

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

  8. Acute intermittent porphyria presenting with posterior reversible encephalopathy syndrome and lateralized periodic discharges plus fast activity on EEG.

    PubMed

    Silveira, Diosely C; Bashir, Mahrukh; Daniel, Joshua; Lucena, Michelle H; Bonpietro, Frank

    2016-01-01

    We report on a 20-year-old patient with a 6-month history of recurrent abdominal pain and a 3-day history of vomiting, hypertension, seizures, and encephalopathy. The brain MRI showed posterior reversible encephalopathy syndrome, and continuous EEG (cEEG) monitoring showed lateralized periodic discharges plus fast activity. Comprehensive CSF studies were negative. Because of severe abdominal pain without a definite etiology, we requested urine porphobilinogen and serum and fecal porphyrins, which suggested acute intermittent porphyria (AIP). The patient had a complete resolution of her symptoms with carbohydrate loading and high caloric diet. Acute intermittent porphyria is potentially life-threatening without proper management and prevention of triggers if it is not recognized.

  9. Acute intermittent porphyria presenting with posterior reversible encephalopathy syndrome and lateralized periodic discharges plus fast activity on EEG.

    PubMed

    Silveira, Diosely C; Bashir, Mahrukh; Daniel, Joshua; Lucena, Michelle H; Bonpietro, Frank

    2016-01-01

    We report on a 20-year-old patient with a 6-month history of recurrent abdominal pain and a 3-day history of vomiting, hypertension, seizures, and encephalopathy. The brain MRI showed posterior reversible encephalopathy syndrome, and continuous EEG (cEEG) monitoring showed lateralized periodic discharges plus fast activity. Comprehensive CSF studies were negative. Because of severe abdominal pain without a definite etiology, we requested urine porphobilinogen and serum and fecal porphyrins, which suggested acute intermittent porphyria (AIP). The patient had a complete resolution of her symptoms with carbohydrate loading and high caloric diet. Acute intermittent porphyria is potentially life-threatening without proper management and prevention of triggers if it is not recognized. PMID:27660746

  10. Acute encephalopathy of the temporal lobes leading to m.3243A>G. When MELAS is not always MELAS.

    PubMed

    Caldarazzo Ienco, Elena; Orsucci, Daniele; Simoncini, Costanza; Montano, Vincenzo; LoGerfo, Annalisa; Siciliano, Gabriele; Bonuccelli, Ubaldo; Mancuso, Michelangelo

    2016-09-01

    MELAS syndrome (mitochondrial encephalopathy with lactic acidosis and stroke-like episodes) is a rare genetic condition whose differential diagnosis is often posed with juvenile stroke, but more rarely even with inflammatory/infectious encephalitis, causing diagnostic challenges. Here we report the case of a young man harbouring the m.3243A>G MELAS mutation presenting an acute onset mimicking the clinical and neuroimaging features of infective encephalitis.

  11. [Recurrent posterior reversible encephalopathy due to vasospasm and cerebral hypoperfusionin in acute leukemia: a case report].

    PubMed

    Hiraide, Takuya; Matsubayashi, Tomoko; Ishigaki, Hidetoshi; Asahina, Miki; Sakaguchi, Kimiyoshi; Fukuda, Tokiko

    2015-11-01

    We report the case of a 4-year-old girl who presented with recurrent posterior reversible encephalopathy syndrome (PRES). She was diagnosed with B-precursor acute lymphocytic leukemia (ALL), and was administered remission-induction chemotherapy. On day 28 of the induction therapy, she experienced seizure and prolonged unconsciousness. Blood pressure was slightly elevated. MRI revealed cortical cytotoxic edema in the right temporal and occipital lobes. In the right occipital white matter the lesion with vasogenic edema also existed. Three days later, MRI showed vasogenic edema in subcortical white matter of the right temporal right occipital and bilateral occipital lobes. The lesions had receded with time. Since the seizure occurred, the chemotherapy had been discontinued. The episodes of seizure and prolonged consciousness recurred 22 days later. MRI revealed vasogenic edema in the right occipital lobe, and MR angiography demonstrated vessel irregularity and reduced branch visualization in the middle and posterior cerebral arteries. Arterial spin-labeling (ASL) showed hypoperfusion in both occipital lobes. It suggests that vasoconstriction and hypoperfusion could lead to recurrent PRES in this case. It is possible that ASL might be more sensitive than MRI in detecting the lesions of PRES. It should be noted that PRES might recur in leukemia. PMID:26717647

  12. A new approach to define acute kidney injury in term newborns with hypoxic ischemic encephalopathy

    PubMed Central

    Gupta, Charu; Massaro, An N.

    2016-01-01

    Background Current definitions of acute kidney injury (AKI) are not sufficiently sensitive to identify all newborns with AKI during the first week of life. Methods To determine whether the rate of decline of serum creatinine (SCr) during the first week of life can be used to identify newborns with AKI, we reviewed the medical records of 106 term neonates at risk of AKI who were treated with hypothermia for hypoxic ischemic encephalopathy (HIE). Results Of the newborns enrolled in the study, 69 % showed a normal rate of decline of SCr to ≥50 % and/or reached SCr levels of ≤0.6 mg/dl before the 7th day of life, and therefore had an excellent clinical outcome (control group). Thirteen newborns with HIE (12 %) developed AKI according to an established neonatal definition (AKI–KIDGO group), and an additional 20 newborns (19 %) showed a rate of decline of SCr of <33, <40, and <46 % from birth to days 3, 5, or 7 of life, respectively (delayed rise in estimated SCr clearance group). Compared to the control group, newborns in the other two groups required more days of mechanical ventilation and vasopressor drugs and had higher gentamicin levels, more fluid overload, lower urinary epidermal growth factor levels, and a prolonged length of stay. Conclusions The rate of decline of SCr provides a sensitive approach to identify term newborns with AKI during the first week of life. PMID:26857710

  13. A case of acute post-streptococcal glomerulonephritis that developed posterior reversible encephalopathy syndrome.

    PubMed

    Kasap, Belde; Çarman, Kürşat Bora; Yiş, Uluç

    2014-12-01

    A 10-year male patient presented with swelling in the face, legs and scrotal area which developed 8 days after tonsillitis treatment. Acute post-sterotococcal glomerulonephritis (APSGN) was considered in the patient whose urinalysis revealed hematuria and proteinuria at nephrotic level, whose urea, creatinine, lipid profile and anti-streptolysine O antibody levels were increased, albumin and C3 value were decreased and whose 24-hour urine test revealed proteinuria. Renal biopsy was found to be compatible with APSGN. In the follow-up, severe headache, vomiting and convulsion were observed under antihypertensive and diuretic treatment and when the blood pressure was 130/80 mmHg (the 99(th) percentile for the patient: 129/88 mmHg). During the follow-up, the blood pressure values increased to 160/90 mmHg. The electroencephalogram (EEG) performed was found to be normal and magnetic resonance imaging (MRI) findings were compatible with posterior reversible encephalopathy syndrome (PRES). MRI was found to be normal at the first month following antihypertensive and anticonvulsive treatment. In the first year of the follow-up, the blood pressure, neurological examination and urinalysis findings were found to be normal. This patient was presented to draw attention to the fact that PRES can also present with a blood pressure tending to increase and with blood pressure values which are not so high. PMID:26078688

  14. Acute necrotising encephalopathy in a child with H1N1 influenza infection: a clinicoradiological diagnosis and follow-up.

    PubMed

    Yoganathan, Sangeetha; Sudhakar, Sniya Valsa; James, Ebor Jacob; Thomas, Maya Mary

    2016-01-11

    Acute necrotising encephalopathy of childhood (ANEC) is a fulminant disorder with rapid progressive encephalopathy, seizures and poor outcome. It has been reported in association with various viral infections. We describe the clinicoradiological findings and short-term follow-up in a child with H1N1 influenza-associated ANEC. Laminar, target or tricolour pattern of involvement of the thalami was seen on apparent diffusion coefficient images. Our patient had significant morbidity at discharge despite early diagnosis and management with oseltamivir and immunoglobulin. Repeat imaging after 3 months had shown significant resolution of thalamic swelling, but there was persistence of cytotoxic oedema involving bilateral thalami. She was pulsed with intravenous steroids and maintained on a tapering schedule of oral steroids. This report emphasises the need for a high index of suspicion to establish early diagnosis, promotion of widespread immunisation strategies to prevent influenza outbreak, and more research to establish standard treatment protocols for this under-recognised entity.

  15. A novel autoantibody against ephrin type B receptor 2 in acute necrotizing encephalopathy

    PubMed Central

    2013-01-01

    Acute necrotizing encephalopathy (ANE) is characterized by symmetrical brain necrosis, suggested to be due to breakdown of the blood–brain barrier (BBB). We experienced a rare case of ANE complicated with systemic lupus erythematosus (SLE), and found that the patient’s serum (V10-5) had binding activity to human umbilical vein endothelial cells (HUVECs). By SARF (Serological identification system for Autoantigens using a Retroviral vector and Flow cytometry) method using V10-5 IgG, a clone bound to V10-5 IgG was isolated. This cell clone was integrated with cDNA identical to EphB2, which plays critical roles in neuronal cells and endothelial cells. HUVECs and human brain microvascular endothelial cells expressed EphB2 and the V10-5 IgG bound specifically to EphB2-transfected cells. Anti-EphB2 antibody was not detected in other SLE patients without ANE. In this report, we identified EphB2 as a novel autoantigen, and anti-EphB2 antibody may define a novel group of brain disorders. Anti-EphB2 antibody can interfere not only with endothelial cells including those of the BBB (acting as an anti-endothelial cell antibody), but also neuronal cells (acting as an anti-neuronal antibody) if the BBB has been breached. Future studies should determine the clinical prevalence and specificity of anti-EphB2 antibody, and the molecular mechanisms by which anti-EphB2 antibody mediates neuronal and vascular pathological lesions. PMID:24139226

  16. A novel autoantibody against ephrin type B receptor 2 in acute necrotizing encephalopathy.

    PubMed

    Shirai, Tsuyoshi; Fujii, Hiroshi; Ono, Masao; Watanabe, Ryu; Shirota, Yuko; Saito, Shinichiro; Ishii, Tomonori; Nose, Masato; Harigae, Hideo

    2013-10-18

    Acute necrotizing encephalopathy (ANE) is characterized by symmetrical brain necrosis, suggested to be due to breakdown of the blood-brain barrier (BBB). We experienced a rare case of ANE complicated with systemic lupus erythematosus (SLE), and found that the patient's serum (V10-5) had binding activity to human umbilical vein endothelial cells (HUVECs). By SARF (Serological identification system for Autoantigens using a Retroviral vector and Flow cytometry) method using V10-5 IgG, a clone bound to V10-5 IgG was isolated. This cell clone was integrated with cDNA identical to EphB2, which plays critical roles in neuronal cells and endothelial cells. HUVECs and human brain microvascular endothelial cells expressed EphB2 and the V10-5 IgG bound specifically to EphB2-transfected cells. Anti-EphB2 antibody was not detected in other SLE patients without ANE. In this report, we identified EphB2 as a novel autoantigen, and anti-EphB2 antibody may define a novel group of brain disorders. Anti-EphB2 antibody can interfere not only with endothelial cells including those of the BBB (acting as an anti-endothelial cell antibody), but also neuronal cells (acting as an anti-neuronal antibody) if the BBB has been breached. Future studies should determine the clinical prevalence and specificity of anti-EphB2 antibody, and the molecular mechanisms by which anti-EphB2 antibody mediates neuronal and vascular pathological lesions.

  17. Human African trypanosomiasis (T.b. gambiense): a study of 16 fatal cases of sleeping sickness with some observations on acute reactive arsenical encephalopathy.

    PubMed

    Adams, J H; Haller, L; Boa, F Y; Doua, F; Dago, A; Konian, K

    1986-01-01

    The principal clinical and pathological findings in 16 fatal cases of human African trypanosomiasis caused by T.b. Gambiense are described. The changes in the brain took the form of a non-specific lymphoplasmacytic meningo-encephalitis of varying intensity. Other features included morular cells, diffuse microglial hyperplasia, and large reactive astrocytes in the white matter. Carditis was identified in 10 cases. Acute reactive arsenical encephalopathy appeared to be the principal cause of death in 10 patients. Convulsions figured prominently in this type of encephalopathy in seven patients and were sufficiently severe to produce hypoxic brain damage. In three cases of acute reactive arsenical encephalopathy the structural changes in the brain were those of acute haemorrhagic leucoencephalopathy.

  18. Dengue encephalopathy.

    PubMed

    Hendarto, S K; Hadinegoro, S R

    1992-06-01

    Dengue encephalopathy or dengue hemorrhagic fever (DHF) with CNS involvement used to be considered a relatively rare condition; but the number of cases reported in human studies has been increasing every year. Diagnosis of dengue encephalopathy is based on clinically diagnosed DHF according to the W.H.O. criteria (1980), with CNS manifestations consisting of abrupt onset of hyperpyrexia, non-transient alteration of consciousness, headache, vomiting--with or without seizures--and normal CSF. Many factors may be considered to be directly or indirectly associated with CNS signs and symptoms in DHF, the main pathology being leakage of plasma into serous spaces and abnormal hemostasis, leading to hypovolemic shock and hemorrhage in many organs of the body. Acute liver failure is considered to be one of the main factors causing brain pathology. One hundred fifty-two cases of dengue encephalopathy admitted during 3 periods at the Cipto Mangunkusumo Hospital in Jakarta were studied retrospectively. The overall incidence was 152 out of 2,441 DHF cases, or 6.2%. The most pronounced symptoms were hyperpyrexia, alteration of consciousness and convulsions. Laboratory examination showed an unusually high increase of serum transaminases, hyponatremia, and hypoxia. Neurologic abnormalities detected were hemiparesis and tetraparesis of the extremities, and second nerve atrophy; such abnormalities were found in 10 out of the 152 cases, or 6.5%.

  19. [Scapular and vertebral osteopathies during acute myoclonic bismuth encephalopathies. Apropos of 8 cases].

    PubMed

    Emile, J; De Bray, J M; Bernat, M; Morer, T; Allain, P

    1979-01-01

    Among 59 cases of bismuth encephalopathy, 8 patients were observed to have osteo-articular lesions of the shoulders and dorsal vertebral. These included osteonecrosis of the head of the humerus, which has been reported previously, uni- or bi-lateral fractures of the upper end of the humerus, and vertebral fractures. Severe and repeated myoclonic spasms appear to be capable of causing fractures; microscopic fractures in the spongy bone could explain the osteonecrotic images observed. PMID:434718

  20. Hemolytic-uremic syndrome with acute encephalopathy in a pregnant woman infected with epidemic enterohemorrhagic Escherichia coli: characteristic brain images and cytokine profiles.

    PubMed

    Ito, M; Shiozaki, A; Shimizu, M; Saito, S

    2015-05-01

    A food-poisoning outbreak due to enterohemorrhagic Escherichia coli (EHEC) occurred in Toyama, Japan. The case of a 26-year-old pregnant woman with hemolytic-uremic syndrome who developed acute encephalopathy due to EHEC infection after eating raw meat is presented herein. On day 2 following admission, a cesarean section was performed because of a non-reassuring fetal status. Fecal bacterial culture confirmed an O111/O157 superinfection. Intensive care therapies including continuous hemodiafiltration and plasma exchange were performed. After the operation, the patient developed encephalopathy for which steroid pulse therapy was added. Her condition improved gradually and she was discharged 55 days after delivery.

  1. Hepatic encephalopathy: a review.

    PubMed

    Lizardi-Cervera, Javier; Almeda, Paloma; Guevara, Luis; Uribe, Misael

    2003-01-01

    Hepatic encephalopathy (HE) is a complication that presents in as many as 28% of patients with cirrhosis, and reported up to ten years after the diagnosis of cirrhosis. Commonly, it is observed in patients with severe hepatic failure and is characterized by neuropsychiatric manifestations that can range in severity from a mild alteration in mental state to a coma; additionally, some neuromuscular symptoms can be observed. This complication of either acute or chronic hepatic disease is the result of a diminished hepatic reservoir and inability to detoxify some toxins that originate in the bowel. Today, the role of astrocytes, specifically the Alzheimer type II cells, is known to be very important in the pathogenesis of the hepatic encephalopathy, and will be reviewed later. In conclusion, the objectives of this review are: To understand the pathogenesis of hepatic encephalopathy, To recognize the precipitating factors, as well as preventive measures for the development of the hepatic encephalopathy, To describe the new classification of hepatic encephalopathy and its clinical implications, To recognize the clinical manifestations and stages of the disease, To understand the main diagnostic tests used to detect the hepatic encephalopathy, To describe the main therapeutic treatments of hepatic encephalopathy. PMID:15115963

  2. [A young patient of acute encephalitis complicated with acyclovir encephalopathy without renal dysfunction].

    PubMed

    Tomori, Koji; Isozumi, Kazuo; Motohashi, Sachiko; Komatsumoto, Satoru; Fukuuchi, Yasuo

    2003-08-01

    A previously healthy 30-year-old woman was admitted to our hospital because of impaired consciousness after convulsion. A temporary diagnosis of herpes simplex encephalitis was made, and intravenous acyclovir (ACV) therapy (250 mg four times daily in normal saline over 2 hours) was started. Three days later, she became confused, and was having hallucinations, dysarthria and generalized painful seizures occurred without focal neurologic deficit. Whether the neuropsychiatric symptoms were related to herpes simplex encephalitis or acyclovir neurotoxity was initially unclear. The brain MRI and lumbar puncture findings were initially normal, but abnormal FLAIR lesions appeared later. ACV-associated encephalopathy was considered. ACV was discontinued, and she recovered from the neurological disorder within 24 hours. Although blood levels of acyclovir were not determined, it is unlikely that they were in a toxic range, in view of her normal renal function.

  3. MR Imaging Findings in Alcoholic and Nonalcoholic Acute Wernicke's Encephalopathy: A Review

    PubMed Central

    Manzo, Gaetana; De Gennaro, Angela; Cozzolino, Attilio; Serino, Antonietta; Fenza, Giacomo; Manto, Andrea

    2014-01-01

    Wernicke's encephalopathy (WE) is a severe neurological syndrome caused by thiamine (vitamin B1) deficiency and clinically characterized by the sudden onset of mental status changes, ocular abnormalities, and ataxia. Apart from chronic alcoholism, the most common cause of WE, a lot of other conditions causing malnutrition and decreasing thiamine absorption such as gastrointestinal surgical procedures and hyperemesis gravidarum must be considered as predisposing factors. Due to its low prevalence and clinical heterogeneity, WE is often misdiagnosed, leading to persistent dysfunctions and, in some cases, to death. Nowadays, MR imaging of the brain, showing T2 and FLAIR hyperintensities in typical (thalami, mammillary bodies, tectal plate, and periaqueductal area) and atypical areas (cerebellum, cranial nerve nuclei, and cerebral cortex), is surely the most important and effective tool in the diagnostic assessment of WE. The aim of this paper is to propose a state of the art of the role of MR imaging in the early diagnosis of this complex disease. PMID:25050351

  4. Infusion of branched-chain enriched amino acid solution in patients with hepatic encephalopathy.

    PubMed

    Freund, H; Dienstag, J; Lehrich, J; Yoshimura, N; Bradford, R R; Rosen, H; Atamian, S; Slemmer, E; Holroyde, J; Fischer, J E

    1982-08-01

    Hospitalized patients with hepatic insufficiency often suffer from severe catabolic states and are in urgent need of nutritional support during their acute illness. Protein intolerence, however, remains a significant problem with respect to the provision of adequate nutrition, either enterally or parenterally. The following report is an anecdotal series of 63 consecutive patients in a large urban hospital treated prospectively with nutritional support using a prototype high branched-chain amino acid solution (FO80) given by technique of total parenteral nutrition by the subclavian or internal jugular route with hypertonic dextrose. Sixty-three patients, of which 42 had chronic liver disease (cirrhosis) with acute decompensation and 17 with acute hepatic injury as well as four with hepatorenal syndrome, are the subject of this report. All required intravenous nutritional support and were either intolerant to commercially available parenteral nutrition solutions or were in hepatic encephalopathy at the time they were initially seen. The cirrhotic patients had been hospitalized for a mean of 14.5 +/- 1.9 days before therapy, had a mean bilirubin of 13 mg/100 ml, and had been in coma for 4.8 +/- 0.7 days despite standard therapy. Patients with acute hepatitis had been in the hospital for 16.2 +/- 4.1 days before therapy, had a mean bilirubin of 25 mg/100 ml, and had been in coma 5.2 +/- 1.6 days before therapy. Routine tests of liver function, blood chemistries, amino acids, EEGs, and complex neurological testing including Reitan trailmaking tests were used in the evaluation of these patients. Up to 120 grams of synthetic amino acid solution with hypertonic dextrose was tolerated in these patients with improvement noted in encephalopathy of at least one grade in 87% of the patients with cirrhosis and 75% of the patients with hepatitis. Nitrogen balance was achieved when 75 to 80 grams of synthetic amino acids were administered. Survival was 45% in the cirrhotic group

  5. Epidemiological analysis of a large enterohaemorrhagic Escherichia coli O111 outbreak in Japan associated with haemolytic uraemic syndrome and acute encephalopathy.

    PubMed

    Yahata, Y; Misaki, T; Ishida, Y; Nagira, M; Watahiki, M; Isobe, J; Terajima, J; Iyoda, S; Mitobe, J; Ohnishi, M; Sata, T; Taniguchi, K; Tada, Y; Okabe, N

    2015-10-01

    A large outbreak of enterohaemorrhagic Escherichia coli (EHEC) O111 and O157 occurred in Japan in April 2011. We conducted an unmatched case-control study and trace-back investigation to determine the source of EHEC O111 infection and risk factors for severe complications. Pulsed-field gel electrophoresis was performed to help define cases. A total of 86 individuals met the case definition. Of these, 40% experienced haemolytic uraemic syndrome (HUS), 24% acute encephalopathy, and 6% died. Illness was significantly associated with eating the raw beef dish yukhoe (odds ratio 19·64, 95% confidence interval 7·03-54·83), the likely food vehicle. EHEC O111 and its closely related stx-negative variants were found in the beef. HUS occurred most frequently in individuals aged 5-9 years, and this age group was significantly associated with acute encephalopathy. The prevalence of HUS and acute encephalopathy was higher than in previous non-O157-related outbreaks, indicating a high risk of severe complications. PMID:25600435

  6. Inherited Disorders of Bilirubin Clearance

    PubMed Central

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

    2016-01-01

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

  7. Inherited disorders of bilirubin clearance.

    PubMed

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

    2016-03-01

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

  8. Toxic Encephalopathy

    PubMed Central

    Kim, Jae Woo

    2012-01-01

    This article schematically reviews the clinical features, diagnostic approaches to, and toxicological implications of toxic encephalopathy. The review will focus on the most significant occupational causes of toxic encephalopathy. Chronic toxic encephalopathy, cerebellar syndrome, parkinsonism, and vascular encephalopathy are commonly encountered clinical syndromes of toxic encephalopathy. Few neurotoxins cause patients to present with pathognomonic neurological syndromes. The symptoms and signs of toxic encephalopathy may be mimicked by many psychiatric, metabolic, inflammatory, neoplastic, and degenerative diseases of the nervous system. Thus, the importance of good history-taking that considers exposure and a comprehensive neurological examination cannot be overemphasized in the diagnosis of toxic encephalopathy. Neuropsychological testing and neuroimaging typically play ancillary roles. The recognition of toxic encephalopathy is important because the correct diagnosis of occupational disease can prevent others (e.g., workers at the same worksite) from further harm by reducing their exposure to the toxin, and also often provides some indication of prognosis. Physicians must therefore be aware of the typical signs and symptoms of toxic encephalopathy, and close collaborations between neurologists and occupational physicians are needed to determine whether neurological disorders are related to occupational neurotoxin exposure. PMID:23251840

  9. Optical transcutaneous bilirubin detector

    DOEpatents

    Kronberg, J.W.

    1993-11-09

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

  10. Optical transcutaneous bilirubin detector

    DOEpatents

    Kronberg, James W.

    1993-01-01

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

  11. Optical transcutaneous bilirubin detector

    DOEpatents

    Kronberg, J.W.

    1991-03-04

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

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

    PubMed

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

    2016-06-20

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

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

    PubMed

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

    2016-06-20

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

  14. Metabolic encephalopathies.

    PubMed

    Angel, Michael J; Young, G Bryan

    2011-11-01

    Kinnier Wilson coined the term metabolic encephalopathy to describe a clinical state of global cerebral dysfunction induced by systemic stress that can vary in clinical presentation from mild executive dysfunction to deep coma with decerebrate posturing; the causes are numerous. Some mechanisms by which cerebral dysfunction occurs in metabolic encephalopathies include focal or global cerebral edema, alterations in transmitter function, the accumulation of uncleared toxic metabolites, postcapillary venule vasogenic edema, and energy failure. This article focuses on common causes of metabolic encephalopathy, and reviews common causes, clinical presentations and, where relevant, management.

  15. Eosinophilic Fasciitis and Acute Encephalopathy Toxicity from Pembrolizumab Treatment of a Patient with Metastatic Melanoma.

    PubMed

    Khoja, Leila; Maurice, Catherine; Chappell, MaryAnne; MacMillan, Leslie; Al-Habeeb, Ayman S; Al-Faraidy, Nada; Butler, Marcus O; Rogalla, Patrik; Mason, Warren; Joshua, Anthony M; Hogg, David

    2016-03-01

    Anti-PD-1 inhibitors have significant activity in metastatic melanoma. Responses often occur early and may be sustained. The optimal duration of treatment with these agents is unknown. Here, we report the case of a 51-year-old woman treated with pembrolizumab, as part of the Keynote-001 trial, as first-line treatment for metastatic disease. She experienced a complete response after 13.8 months of treatment with no adverse events. One month after the last drug infusion and 18 months from starting treatment, the patient presented with eosinophilic fasciitis. She then developed acute confusion and weakness, thought to be due to intracranial vasculitis. High-dose steroids were initiated with resolution of the fasciitis. Aspirin was commenced for presumed vasculitis with resolution of the neurologic symptoms. To our knowledge, there are no previous reports of eosinophilic fasciitis or cerebral vasculitis due to anti-PD-1 agents. This case demonstrates that toxicity may occur in association with pembrolizumab treatment after a prolonged period of treatment without toxicity. Future trials should explore the optimal duration of treatment with pembrolizumab.

  16. Eosinophilic Fasciitis and Acute Encephalopathy Toxicity from Pembrolizumab Treatment of a Patient with Metastatic Melanoma.

    PubMed

    Khoja, Leila; Maurice, Catherine; Chappell, MaryAnne; MacMillan, Leslie; Al-Habeeb, Ayman S; Al-Faraidy, Nada; Butler, Marcus O; Rogalla, Patrik; Mason, Warren; Joshua, Anthony M; Hogg, David

    2016-03-01

    Anti-PD-1 inhibitors have significant activity in metastatic melanoma. Responses often occur early and may be sustained. The optimal duration of treatment with these agents is unknown. Here, we report the case of a 51-year-old woman treated with pembrolizumab, as part of the Keynote-001 trial, as first-line treatment for metastatic disease. She experienced a complete response after 13.8 months of treatment with no adverse events. One month after the last drug infusion and 18 months from starting treatment, the patient presented with eosinophilic fasciitis. She then developed acute confusion and weakness, thought to be due to intracranial vasculitis. High-dose steroids were initiated with resolution of the fasciitis. Aspirin was commenced for presumed vasculitis with resolution of the neurologic symptoms. To our knowledge, there are no previous reports of eosinophilic fasciitis or cerebral vasculitis due to anti-PD-1 agents. This case demonstrates that toxicity may occur in association with pembrolizumab treatment after a prolonged period of treatment without toxicity. Future trials should explore the optimal duration of treatment with pembrolizumab. PMID:26822024

  17. Bilirubin measurements in neonates

    NASA Astrophysics Data System (ADS)

    Newman, Gregory J.

    2000-04-01

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

  18. Aquaporin-4 Deletion in Mice Reduces Encephalopathy and Brain Edema in Experimental Acute Liver Failure

    PubMed Central

    Rama Rao, Kakulavarapu V.; Verkman, A. S.; Curtis, Kevin M.; Norenberg, Michael D.

    2014-01-01

    Brain edema and associated astrocyte swelling leading to increased intracranial pressure are hallmarks of acute liver failure (ALF). Elevated blood and brain levels of ammonia have been implicated in the development of brain edema in ALF. Cultured astrocytes treated with ammonia have been shown to undergo cell swelling and such swelling was associated with an increase in the plasma membrane expression of aquaporin-4 (AQP4) protein. Further, silencing the AQP4 gene in cultured astrocytes was shown to prevent the ammonia-induced cell swelling. Here, we examined the evolution of brain edema in AQP4-null mice and their wild type counterparts (WT-mice) in different models of ALF induced by thioacetamide (TAA) or acetaminophen (APAP). Induction of ALF with TAA or APAP significantly increased brain water content in WT mice (by 1.6 ± 0.3 and 2.3 ± 0.4 %, respectively). AQP4 protein was significantly increased in brain plasma membranes of WT mice with ALF induced by either TAA or APAP. In contrast to WT-mice, brain water content did not increase in AQP4-null mice. Additionally, AQP4-null mice treated with either TAA or APAP showed a remarkably lesser degree of neurological deficits as compared to WT mice; the latter displayed an inability to maintain proper gait, and demonstrated a markedly reduced exploratory behavior, with the mice remaining in one corner of the cage with its head tilted downwards. These results support a central role of AQP4 in the brain edema associated with ALF. PMID:24321433

  19. [Hashimoto's encephalopathy and autoantibodies].

    PubMed

    Yoneda, Makoto

    2013-04-01

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

  20. Hepatic encephalopathy.

    PubMed

    Córdoba, Juan; Mínguez, Beatriz

    2008-02-01

    Hepatic encephalopathy is a severe complication of cirrhosis that is related to the effects of ammonia. Analysis of interorgan ammonia trafficking has identified an important role of skeletal muscle in ammonia removal and has highlighted the importance of the nutritional status. Ammonia causes neurotransmitter abnormalities and induces injury to astrocytes that is partially mediated by oxidative stress. These disturbances lead to astrocyte swelling and brain edema, which appear to be involved in the pathogenesis of neurological manifestations. Inflammatory mediators worsen brain disturbances. New methods for assessing hepatic encephalopathy include clinical scales, neuropsychological tests, imaging of portal-systemic circulation, and magnetic resonance of the brain. Reappraisal of current therapy indicates the need for performing placebo-controlled trials and the lack of evidence for administering diets with restricted protein content. Liver transplant should be considered in selected patients with hepatic encephalopathy. Future prospects include new drugs that decrease plasma ammonia, measures to reduce brain edema, and liver-support devices. PMID:18293278

  1. Infection-Triggered Familial or Recurrent Cases of Acute Necrotizing Encephalopathy Caused by Mutations in a Component of the Nuclear Pore, RANBP2

    PubMed Central

    Neilson, Derek E.; Adams, Mark D.; Orr, Caitlin M.D.; Schelling, Deborah K.; Eiben, Robert M.; Kerr, Douglas S.; Anderson, Jane; Bassuk, Alexander G.; Bye, Ann M.; Childs, Anne-Marie; Clarke, Antonia; Crow, Yanick J.; Di Rocco, Maja; Dohna-Schwake, Christian; Dueckers, Gregor; Fasano, Alfonso E.; Gika, Artemis D.; Gionnis, Dimitris; Gorman, Mark P.; Grattan-Smith, Padraic J.; Hackenberg, Annette; Kuster, Alice; Lentschig, Markus G.; Lopez-Laso, Eduardo; Marco, Elysa J.; Mastroyianni, Sotiria; Perrier, Julie; Schmitt-Mechelke, Thomas; Servidei, Serenella; Skardoutsou, Angeliki; Uldall, Peter; van der Knaap, Marjo S.; Goglin, Karrie C.; Tefft, David L.; Aubin, Cristin; de Jager, Philip; Hafler, David; Warman, Matthew L.

    2009-01-01

    Acute necrotizing encephalopathy (ANE) is a rapidly progressive encephalopathy that can occur in otherwise healthy children after common viral infections such as influenza and parainfluenza. Most ANE is sporadic and nonrecurrent (isolated ANE). However, we identified a 7 Mb interval containing a susceptibility locus (ANE1) in a family segregating recurrent ANE as an incompletely penetrant, autosomal-dominant trait. We now report that all affected individuals and obligate carriers in this family are heterozygous for a missense mutation (c.1880C→T, p.Thr585Met) in the gene encoding the nuclear pore protein Ran Binding Protein 2 (RANBP2). To determine whether this mutation is the susceptibility allele, we screened controls and other patients with ANE who are unrelated to the index family. Patients from 9 of 15 additional kindreds with familial or recurrent ANE had the identical mutation. It arose de novo in two families and independently in several other families. Two other patients with familial ANE had different RANBP2 missense mutations that altered conserved residues. None of the three RANBP2 missense mutations were found in 19 patients with isolated ANE or in unaffected controls. We conclude that missense mutations in RANBP2 are susceptibility alleles for familial and recurrent cases of ANE. PMID:19118815

  2. Acute encephalopathy associated with hemolytic uremic syndrome caused by Escherichia coli O157: H7 and rotavirus infection.

    PubMed

    Imataka, G; Wake, K; Suzuki, M; Yamanouchi, H; Arisaka, O

    2015-05-01

    We reported a case of a 22-months child with hemolytic uremic syndrome associated with encephalopathy. As the cause of this case, the involvements of verotoxin 1 and 2 caused by O157: the H7 strain of the enterohemorrhagic Escherichia coli and rotavirus were presumed. We administered brain hypothermic therapy and steroid pulse therapy in the intensive care unit, but we were not able to save his life and the child died on the 6th day from the onset.

  3. Bilirubin present in diverse angiosperms

    PubMed Central

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

    2010-01-01

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

  4. [Hashimoto encephalopathy].

    PubMed

    Pocsay, Gábor; Gazdag, Andrea; Engelhardt, József; Szaniszló, István; Szolnoki, Zoltán; Forczek, Gabriella; Mikló, László

    2013-08-18

    The authors present a case report and review the literature on Hashimoto encephalopathy. The onset of the disease may be marked by focal and then progressively generalized seizures or other neurological symptoms, but a cognitive decline or various psychiatric symptoms may also emerge. High levels of anti-thyroid peroxidase antibodies and/or anti-thyroglobulin antibodies are present in the serum. Corticosteroid treatment usually results in an improvement of symptoms. The syndrome is frequently overlooked and, therefore, the authors strongly recommend testing serum thyroid autoantibodies in cases with encephalopathy of unknown origin independently on the presence of thyroid disease in the patient or family history. The importance of long-term immunosuppressive treatment should also be stressed.

  5. The Biological Effects of Bilirubin Photoisomers.

    PubMed

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

    2016-01-01

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

  6. Hashimoto's encephalopathy.

    PubMed

    Schiess, Nicoline; Pardo, Carlos A

    2008-10-01

    Hashimoto's encephalopathy (HE) is a controversial neurological disorder that comprises a heterogenous group of neurological symptoms that manifest in patients with high titers of antithyroid antibodies. Clinical manifestations of HE may include encephalopathic features such as seizures, behavioral and psychiatric manifestations, movement disorders, and coma. Although it has been linked to cases of Hashimoto's thyroiditis or thyroid dysfunction, the most common immunological feature of HE is the presence of high titers of antithyroglobulin or anti-TPO (antimicrosomal) antibodies. At present, it is unclear whether antithyroid antibodies represent an immune epiphenomenon in a subset of patients with encephalopathic processes or they are really associated with pathogenic mechanisms of the disorder. The significance of classifying encephalopathies under the term HE will be determined in the future once the relevance of the role of antithyroid antibodies is demonstrated or dismissed by more detailed experimental and immunopathological studies. The responsiveness of HE to steroids or other therapies such as plasmapheresis supports the hypothesis that this is a disorder that involves immune pathogenic mechanisms. Further controlled studies of the use of steroids, plasmapheresis, or immunosuppressant medications are needed in the future to prove the concept of the pathogenic role of antithyroid antibodies in HE. PMID:18990131

  7. Reversible laminar signal intensity in deep cortical gray matter in T1-weighted images and FLAIR after mild acute hyperammonemic hepatic encephalopathy.

    PubMed

    Treusch, N A; van de Loo, S; Hattingen, E

    2012-12-01

    Soporific acute hyperammonemic hepatic encephalopathy (aHE) can induce considerable changes in cerebral white and gray matter. This report describes a patient in the subacute phase of aHE grade I without disturbed consciousness and with reversible fine laminar cortical involvement on magnetic resonance imaging (MRI). The 59-year-old patient had esophageal varices bleeding due to primary biliary cirrhosis (ammonium blood level: 140 mmoL/L) and presented with sensory Jacksonian seizures, dysarthria, and increased drowsiness and fatigue. MRI revealed patchy hyperintense (T2-weighted, T2w) white-matter lesions and bilateral signal intensities in the striatum (T1w). During a rise of ammonium blood level to 220 mmoL/L, the patient had increased drowsiness, persistent dysarthria and mild temporary hemiparesis without loss of consciousness. Two weeks later, the patient was asymptomatic and blood ammonium level had reverted to normal value. MRI at that time revealed bihemispheric fine laminar subcortical hyperintensities on T2w and fluid-attenuated inversion recovery (FLAIR) imaging, and partially on T1w sequences, with no swelling or restricted diffusion; the hyperintensities were fully reversible a month later. Such a distinct cortical signal increase not only on T2w images, but also on T1w, in a patient after a mild form of aHE is a new MR finding.

  8. Mechanisms of acute uremic encephalopathy: early activation of Fos and Fra-2 gene products in different nuclei/areas of the rat brain.

    PubMed

    Heidland, August; Sebekova, Katarina; Klassen, André; Palkovits, Miklós

    2010-09-01

    High levels of various uremic toxins such as guanidino compounds and advanced glycation endproducts, as well as an excess of parathyroid hormones, are involved in the pathogenesis of acute uremic encephalopathy. Moreover, distant effects of the damaged kidney with enhanced production of inflammatory mediators are implicated. Data on the pump activity of an abnormal Na-K-ATPase and inhibition of the organic anion transporter system in the brain have been published previously. Recently, the effect of an experimentally induced acute renal failure (ARF) on the neuronal cell activation of Fos and Fra-2 in the rat brain was investigated by immunohistochemistry. ARF was induced by using the following 3 rat models: bilateral nephrectomy, bilateral ureter ligation, and uranyl acetate injection with corresponding controls. The Fos and the Fra-2 immunoreactive neurons of the brain were determined in a total of 120 brain areas over a period of 3 days post bilateral nephrectomy and bilateral ureter ligation and 12 days after uranyl acetate. An activation response was observed in 73 of 120 areas of the brain. The responses were classified into 4 groups: (1) biogenic amines (noradrenaline, adrenaline, histamine, and 5-hydroxytryptamine), (2) stress-sensitive forebrain areas, (3) neuronal cell groups involved in the regulation of water and electrolyte homeostasis, and (4) central autonomic cell groups. In the uranyl acetate-induced ARF, activation of Fos and Fra-2 immunoreactivity took place at the earliest time-point (3 hours) which persisted even after improvement of ARF. This suggests the involvement of the toxic effects of uranium as a result of its accumulation in the brain.

  9. The Biological Effects of Bilirubin Photoisomers

    PubMed Central

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

    2016-01-01

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

  10. Hypertension and hypertensive encephalopathy.

    PubMed

    Price, Raymond S; Kasner, Scott E

    2014-01-01

    The definition of hypertension has continuously evolved over the last 50 years. Hypertension is currently defined as a blood pressure greater than 140/90mmHg. One in every four people in the US has been diagnosed with hypertension. The prevalence of hypertension increases further with age, affecting 75% of people over the age of 70. Hypertension is by far the most common risk factor identified in stroke patients. Hypertension causes pathologic changes in the walls of small (diameter<300 microns) arteries and arterioles usually at short branches of major arteries, which may result in either ischemic stroke or intracerebral hemorrhage. Reduction of blood pressure with diuretics, β-blockers, calcium channel blockers, and angiotensin-converting enzyme (ACE) inhibitors have all been shown to markedly reduce the incidence of stroke. Hypertensive emergency is defined as a blood pressure greater than 180/120mmHg with end organ dysfunction, such as chest pain, shortness of breath, encephalopathy, or focal neurologic deficits. Hypertensive encephalopathy is believed to be caused by acute failure of cerebrovascular autoregulation. Hypertensive emergency is treated with intravenous antihypertensive agents to reduce blood pressure by 25% within the first hour. Selective inhibition of cerebrovascular blood vessel permeability for the treatment of hypertensive emergency is beginning early clinical trials.

  11. Autoimmune encephalopathies

    PubMed Central

    Leypoldt, Frank; Armangue, Thaís; Dalmau, Josep

    2014-01-01

    Over the last 10 years the continual discovery of novel forms of encephalitis associated with antibodies to cell-surface or synaptic proteins has changed the paradigms for diagnosing and treating disorders that were previously unknown or mischaracterized. We review here the process of discovery, the symptoms, and the target antigens of twelve autoimmune encephatilic disorders, grouped by syndromes and approached from a clinical perspective. Anti-NMDAR encephalitis, several subtypes of limbic encephalitis, stiff-person spectrum disorders, and other autoimmune encephalitides that result in psychosis, seizures, or abnormal movements are described in detail. We include a novel encephalopathy with prominent sleep dysfunction that provides an intriguing link between chronic neurodegeneration and cell-surface autoimmunity (IgLON5). Some of the caveats of limited serum testing are outlined. In addition, we review the underlying cellular and synaptic mechanisms that for some disorders confirm the antibody pathogenicity. The multidisciplinary impact of autoimmune encephalitis has been expanded recently by the discovery that herpes simplex encephalitis is a robust trigger of synaptic autoimmunity, and that some patients may develop overlapping syndromes, including anti-NMDAR encephalitis and neuromyelitis optica or other demyelinating diseases. PMID:25315420

  12. [Hepatic encephalopathy].

    PubMed

    Festi, Davide; Marasco, Giovanni; Ravaioli, Federico; Colecchia, Antonio

    2016-07-01

    Hepatic encephalopathy (HE) is a common complication of liver cirrhosis and it can manifest with a broad spectrum of neuropsychiatric abnormalities of varying severity, acuity and time course with important clinical implications. According to recent guidelines, HE has been classified into different types, depending on the severity of hepatic dysfunction, the presence of porto-systemic shunts and the number of previous episodes or persistent manifestations. From a clinical point of view, HE can be recognized as unimpaired, covert (that deals with minimal and grade 1 according to the grading of mental state), and overt (that is categorized from grade 2 to grade 4). Different and only partially known pathogenic mechanisms have been identified, comprising ammonia, inflammatory cytokines, benzodiazepine-like compounds and manganese deposition. Different therapeutic strategies are available for treating HE, in particular the overt HE, since covert HE needs to be managed case by case. Recognition and treatment of precipitating factors represent fundamental part of the management. The more effective treatments, which can be performed separately or combined, are represented by non-absorbable disaccharides (lactulose and lactitol) and the topic antibiotic rifaximin; other possible therapies, mainly used in patients non responders to previous treatments, are represented by branched chain amino acids and metabolic ammonia scavengers. PMID:27571468

  13. Association of Proton Pump Inhibitor Therapy with Hepatic Encephalopathy in Hepatitis B Virus-related Acute-on-Chronic Liver Failure

    PubMed Central

    Lin, Zhao-Ni; Zuo, Yong-Qing; Hu, Peng

    2014-01-01

    Background: Hepatic encephalopathy (HE) is an important neuropsychiatry complication of acute-on-chronic liver failure (ACLF). PPI therapy may increase the intestinal bacterial overgrowth and infections. Objectives: The aim of this study was to assess whether PPI use in ACLF is associated with HE. Patients and Methods: A retrospective case-control study was performed. Fifty five admitted patients with hepatitis B virus (HBV)-related ACLF complicated by Stage II-IV HE developed after admission between January 2008 and December 2012 were matched (by sex, age, and MELD score) with comparable HBV-related ACLF patients (n = 110) who did not develop this complication during hospitalization. We excluded combined HE upon admission and other neurological disorders in patients with ACLF. Univariate and multivariate analyses of 30 variables (laboratory examination, predisposition, treatment, etc.) before the occurrence of HE were carried out to identify the factors predictive of HE. Results: In univariate analysis, patients with HE in ACLF had a significantly higher rate of PPI use (89.1%) compared with non-HE (63.6%, P = 0.001). In addition, clinical and standard laboratory variables were significantly different between the two groups regarding the infection rate, hyponatremia, alpha-fetoprotein (AFP), Arginine Hydrochloride use and Lactulose use. Logistic regression analysis was used to examine the combined effects of the variables with HE as the outcome. HE in ACLF was associated with hyponatremia (odds ratio (OR) = 6. 318, 95% confidence interval (CI) = 2. 803-14.241; P = 0. 000), PPI use was independently associated with HE (OR = 4. 392, CI = 1. 604-12.031; P = 0. 004), and lactulose use was protective (OR = 0. 294, CI = 0. 136-0.675; P = 0. 003). Conclusions: The occurrence of HE is associated with hyponatremia and PPI use in patients with ACLF. PMID:24748895

  14. Molecular biology of bilirubin metabolism.

    PubMed

    Jansen, P L; Bosma, P J; Chowdhury, J R

    1995-01-01

    As the genes encoding the glucuronidating enzymes are discovered, it is evident that glucuronidation is a magnificent example of how in evolution, man became adapted to his "intoxicating" environment. A superfamily of genes is necessary to dispose of the toxins and carcinogens that are encountered by inhalation and ingestion. The enzymes that glucuronidate endogenous compounds are members of this large family. For the clinician, it is important to remember that jaundice may sometimes be the result of interactions at the level of bilirubin glucuronidation. When jaundice results from inactivation of members of the UGT1 family, conjugation of certain phenols, such as the anesthetic propofol, or synthetic estrogens, such as ethinylestradiol, can also be impaired. In the case of severe bilirubin glucuronidation deficiencies, such as the Crigler Najjar syndrome type I, there are exciting prospects for a possible cure by gene therapy. PMID:9224500

  15. Bilirubin Binding to PPARα Inhibits Lipid Accumulation.

    PubMed

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

    2016-01-01

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

  16. Bilirubin Binding to PPARα Inhibits Lipid Accumulation

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2007-04-01

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

  18. Bovine Spongiform Encephalopathy

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bovine spongiform encephalopathy (BSE), also referred to as “mad cow disease” is a chronic, non-febrile, neuro-degenerative disease affecting the central nervous system. The transmissible spongiform encephalopathies (TSEs) of domestic animals, of which BSE is a member includes scrapie of sheep...

  19. Hashimoto Encephalopathy or Neurosarcoidosis? A Case Report

    PubMed Central

    Sapkota, Biggya L.; Pitiyanuvath, Nataria

    2015-01-01

    Hashimoto encephalopathy (HE) is a rare autoimmune disease characterized by symptoms of acute or subacute encephalopathy associated with increased antithyroid antibody levels. Neurosarcoidosis is also a rare entity that occurs in less than 5% of patients with systemic sarcoidosis. Neurosarcoidosis usually presents with cranial neuropathies, myelopathy, or new-onset seizure. We report a case of a 49-year-old caucasian woman, previously healthy, who initially presented for a workup of a new-onset seizure. She had a gradually progressive course with neurocognitive decline and recurrent partial seizures refractory to conventional antiepileptic drugs. Her seizures responded well to a course of intravenous immunoglobulin. She was subsequently diagnosed with HE and pulmonary sarcoidosis based on serological and pathological studies. She improved neurologically once the seizures were controlled. Hashimoto encephalopathy is a rare condition that is potentially treatable and presents with various neuropsychiatric manifestations. It is a diagnosis of exclusion that requires a strong clinical suspicion and is often underrecognized. PMID:25829987

  20. Progressive multicystic encephalopathy: is there more than hypoxia-ischemia?

    PubMed

    Garten, Lars; Hueseman, Dieter; Stoltenburg-Didinger, Gisela; Felderhoff-Mueser, Ursula; Weizsaecker, Katharina; Scheer, Ianina; Boltshauser, Eugen; Obladen, Michael

    2007-05-01

    Progressive multicystic encephalopathy following prenatal or perinatal hypoxia-ischemia is a well-described phenomenon in the literature. The authors report on a term infant with a devastating encephalopathy and severe neuronal dysfunction immediately after delivery without a known antecedent of prenatal or perinatal hypoxia or distress. Clinical and paraclinical findings in the patient are compared with those described in the literature. The authors focus on the specific results guiding to the final diagnosis of progressive multicystic encephalopathy and the timing of morphologic changes. As in this case, if the criteria of an acute hypoxic event sufficient to cause neonatal encephalopathy are not met, then factors other than hypoxia-ischemia may be leading to progressive multicystic encephalopathy.

  1. Epileptic Encephalopathies: An Overview

    PubMed Central

    Khan, Sonia; Al Baradie, Raidah

    2012-01-01

    Epileptic encephalopathies are an epileptic condition characterized by epileptiform abnormalities associated with progressive cerebral dysfunction. In the classification of the International League Against Epilepsy eight age-related epileptic encephalopathy syndromes are recognized. These syndromes include early myoclonic encephalopathy and Ohtahara syndrome in the neonatal period, West syndrome and Dravet syndrome in infancy, myoclonic status in nonprogressive encephalopathies, and Lennox-Gastaut syndrome, Landau-Kleffner syndrome, and epilepsy with continuous spike waves during slow wave sleep in childhood and adolescences. Other epileptic syndromes such as migrating partial seizures in infancy and severe epilepsy with multiple independent spike foci may be reasonably added. In this paper, we provide an overview of epileptic encephalopathies including clinical neurophysiological features, cognitive deterioration, and management options especially that these conditions are generally refractory to standard antiepileptic drugs. PMID:23213494

  2. Albumin-bound bilirubin in subchoroidal fluid.

    PubMed

    Lam, W K; Lee, P F; Ray, S; Feman, S; van Heuven, W A

    1979-01-01

    The most unique property of subchoroidal fluid was found to be the high bilirubin level. One distinct yellow band in the same position as albumin was observed when it was subjected to electrophoresis on agarose film. The yellow compound was very soluble in chloroform. Its identity to bilirubin was confirmed by its absorption maximum at 445 nm, and a positive reaction with Ehrlich's diazo reagent. Subretinal fluid and liquid vitreous often had a yellowish appearance after ocular hemorrhage. However, their bilirubin level was not elevated above that of serum. Our data indicated that the degradation of RBCs may be an important causative factor of persistant detachment. PMID:758891

  3. Dengue viral infections as a cause of encephalopathy.

    PubMed

    Malavige, G N; Ranatunga, P K; Jayaratne, S D; Wijesiriwardana, B; Seneviratne, S L; Karunatilaka, D H

    2007-04-01

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

  4. Hepatic encephalopathy: An update of pathophysiologic mechanisms.

    PubMed

    Hazell, A S; Butterworth, R F

    1999-11-01

    Hepatic encephalopathy (HE) is a neuropsychiatric disorder that occurs in both acute and chronic liver failure. Although the precise pathophysiologic mechanisms responsible for HE are not completely understood, a deficit in neurotransmission rather than a primary deficit in cerebral energy metabolism appears to be involved. The neural cell most vulnerable to liver failure is the astrocyte. In acute liver failure, the astrocyte undergoes swelling resulting in increased intracranial pressure; in chronic liver failure, the astrocyte undergoes characteristic changes known as Alzheimer type II astrocytosis. In portal-systemic encephalopathy resulting from chronic liver failure, astrocytes manifest altered expression of several key proteins and enzymes including monoamine oxidase B, glutamine synthetase, and the so-called peripheral-type benzodiazepine receptors. In addition, expression of some neuronal proteins such as monoamine oxidase A and neuronal nitric oxide synthase are modified. In acute liver failure, expression of the astrocytic glutamate transporter GLT-1 is reduced, leading to increased extracellular concentrations of glutamate. Many of these changes have been attributed to a toxic effect of ammonia and/or manganese, two substances that are normally removed by the hepatobiliary route and that in liver failure accumulate in the brain. Manganese deposition in the globus pallidus in chronic liver failure results in signal hyperintensity on T1-weighted Magnetic Resonance Imaging and may be responsible for the extrapyramidal symptoms characteristic of portal-systemic encephalopathy. Other neurotransmitter systems implicated in the pathogenesis of hepatic encephalopathy include the serotonin system, where a synaptic deficit has been suggested, as well as the catecholaminergic and opioid systems. Further elucidation of the precise nature of these alterations could result in the design of novel pharmacotherapies for the prevention and treatment of hepatic

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

    PubMed Central

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

    1996-01-01

    Crigler-Najjar (CN) disease is an inherited disorder of bilirubin metabolism. The disease is caused by a deficiency of the hepatic enzyme bilirubin UDP-glucuronosyltransferase (B-UGT). Patients with CN disease have high serum levels of the toxic compound, unconjugated bilirubin. The only defect in bilirubin metabolism of CN patients is the absence of B-UGT activity. The transplantation of cells able to glucuronidate bilirubin should therefore lower serum bilirubin levels. The Gunn rat is the animal model of CN disease. Primary Gunn rat fibroblasts (GURF) were transduced with a recombinant retrovirus, capable of transferring B-UGT cDNA. A cell line was obtained expressing B-UGT at a level comparable to hepatocytes. Bilirubin added to the culture medium of these cells was glucuronidated and excreted. The B-UGT activities of transduced GURF and freshly isolated Wistar hepatocytes were compared at different bilirubin concentrations. The specific B-UGT activities of these two cell types were comparable when physiological bilirubin concentrations (5-10 microM) were present in the culture media. At higher bilirubin concentrations (20-80 microM) the hepatocytes were more active than the transduced GURF. We conclude that with the addition of only one enzyme (B-UGT) fibroblasts can perform the complete set of reactions necessary for bilirubin glucuronidation. The difference in B-UGT activity between transduced GURF and hepatocytes at 20-80 microM bilirubin can be explained by lower UDP-glucuronic acid and glutathione S-transferase levels in GURF. Our findings also indicate that these cells could be used to develop extrahepatic gene therapy for CN disease. PMID:8670060

  6. Animal pigment bilirubin discovered in plants.

    PubMed

    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

  7. Late onset arginase deficiency presenting with encephalopathy and midbrain hyperintensity.

    PubMed

    Maramattom, Boby Varkey; Raja, Rajat; Balagopal, Anuroop

    2016-01-01

    Urea cycle disorders (UCD) are very rare metabolic disorders that present with encephalopathy and hyperammonemia. Of the UCDs, Arginase deficiency (ARD) is the rarest and presents in childhood with a progressive spastic diplegia or seizures. Acute presentation in adulthood is extremely unusual.[1] We present the first case of adult onset ARD presenting with encephalopathy and diffusion weighted MRI findings that resembled a moustache in the midbrain. PMID:27570396

  8. Late onset arginase deficiency presenting with encephalopathy and midbrain hyperintensity

    PubMed Central

    Maramattom, Boby Varkey; Raja, Rajat; Balagopal, Anuroop

    2016-01-01

    Urea cycle disorders (UCD) are very rare metabolic disorders that present with encephalopathy and hyperammonemia. Of the UCDs, Arginase deficiency (ARD) is the rarest and presents in childhood with a progressive spastic diplegia or seizures. Acute presentation in adulthood is extremely unusual.[1] We present the first case of adult onset ARD presenting with encephalopathy and diffusion weighted MRI findings that resembled a moustache in the midbrain. PMID:27570396

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

    PubMed Central

    Amin, Sanjiv B.; Lamola, Angelo A.

    2011-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2007-06-01

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

  11. Portal systemic encephalopathy.

    PubMed

    Schenker, S; Bay, M K

    1997-05-01

    The goal of this article is to update the status of Portal systemic encephalopathy (PSE) in the light of new data. First, PSE is the context of other types of hepatic encephalopathy. Subsequently, current views of the pathogenesis of the disorder are discussed, followed by an analysis of therapeutic options. Diagnosis will not be considered, as no major new developments have recently been documented in this area.

  12. PPARα: A Master Regulator of Bilirubin Homeostasis

    PubMed Central

    Kaeding, Jenny; El Husseini, Diala; Rudkowska, Iwona; Verreault, Mélanie

    2014-01-01

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

  13. Antioxidant activity of albumin-bound bilirubin.

    PubMed Central

    Stocker, R; Glazer, A N; Ames, B N

    1987-01-01

    Bilirubin, when bound to human albumin and at concentrations present in normal human plasma, protects albumin-bound linoleic acid from peroxyl radical-induced oxidation in vitro. Initially, albumin-bound bilirubin (Alb-BR) is oxidized at the same rate as peroxyl radicals are formed and biliverdin is produced stoichiometrically as the oxidation product. On an equimolar basis, Alb-BR successfully competes with uric acid for peroxyl radicals but is less efficient in scavenging these radicals than vitamin C. These results show that 1 mol of Alb-BR can scavenge 2 mol of peroxyl radicals and that small amounts of plasma bilirubin are sufficient to prevent oxidation of albumin-bound fatty acids as well as of the protein itself. The data indicate a role for Alb-BR as a physiological antioxidant in plasma and the extravascular space. PMID:3475708

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

    PubMed

    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.

  15. The encephalopathy of sepsis.

    PubMed

    Jackson, A C; Gilbert, J J; Young, G B; Bolton, C F

    1985-11-01

    Twelve fatal cases of encephalopathy associated with sepsis were examined in a ten-year retrospective study. The sources of infection and organisms isolated were variable. Six of the patients had focal neurologic signs; five had seizures. The level of consciousness varied from drowsiness to deep coma, and electroencephalograms revealed diffuse or multifocal abnormalities. Computed tomographic head scans and cerebrospinal fluid examinations were usually unremarkable. Eight patients had disseminated microabscesses in the brain at autopsy. Four patients had proliferation of astrocytes and microglia in the cerebral cortex, a feature associated with metabolic encephalopathies. Additional findings included cerebral infarcts, brain purpura, multiple small white matter hemorrhages, and central pontine myelinolysis. Although sepsis may cause encephalopathy by producing disturbances in cerebral synaptic transmission and cerebral energy production through a toxic mechanism, bacterial invasion of the brain with the formation of disseminated microabscesses is also an important cause.

  16. Thiamine in the treatment of Wernicke encephalopathy in patients with alcohol use disorders.

    PubMed

    Latt, N; Dore, G

    2014-09-01

    Wernicke encephalopathy is an acute, reversible neuropsychiatric emergency due to thiamine deficiency. Urgent and adequate thiamine replacement is necessary to avoid death or progression to Korsakoff syndrome with largely irreversible brain damage. Wernicke Korsakoff syndrome refers to a condition where features of Wernicke encephalopathy are mixed with those of Korsakoff syndrome. Although thiamine is the cornerstone of treatment of Wernicke encephalopathy, there are no universally accepted guidelines with regard to its optimal dose, mode of administration, frequency of administration or duration of treatment. Currently, different dose recommendations are being made. We present recommendations for the assessment and treatment of Wernicke encephalopathy based on literature review and our clinical experience.

  17. Serum Bilirubin and Disease Progression in Mild COPD

    PubMed Central

    Apperley, Scott; Park, Hye Yun; Holmes, Daniel T.; Wise, Robert A.; Connett, John E.

    2015-01-01

    BACKGROUND: COPD is a chronic inflammatory disorder associated with oxidative stress. Serum bilirubin has potent antioxidant actions, and higher concentrations have been shown to protect against oxidative stress. The relation between serum bilirubin and COPD progression is unknown. METHODS: Serum bilirubin was measured in 4,680 smokers aged 35 to 60 years old with mild to moderate airflow limitation. The relationship of serum bilirubin to postbronchodilator FEV1 and rate of FEV1 decline over 3 to 9 years was determined using regression modeling. Total and disease-specific mortality were also ascertained. RESULTS: Serum bilirubin was positively related to FEV1 (P < .001). Serum bilirubin was also negatively related to the annual decline in FEV1 when adjusted for baseline demographics, pack-years smoked, and baseline measures of lung function (P = .01). Additionally, serum bilirubin was negatively associated with risk of death from coronary heart disease (P = .03); however, the relationships between bilirubin and other mortality end points were not statistically significant (P > .05). CONCLUSIONS: Bilirubin is inversely related to COPD disease severity and progression. Higher serum bilirubin concentration was associated with a higher FEV1 and less annual decline in FEV1. Bilirubin was also associated with less coronary heart disease mortality. These data support the hypothesis that bilirubin has a protective effect on COPD disease progression, possibly through its antioxidant actions. Bilirubin may prove useful as an easily accessible and readily available blood-based COPD biomarker. PMID:25539285

  18. Immunosuppressive measles encephalopathy.

    PubMed

    Pedersen, F K; Schiøtz, P O; Valerius, N H; Hertz, H

    1978-01-01

    A case of measles infection without a rash, which was followed by a severe encephalopathy after two months, is described in a 2 1/2 year old boy. At the age of 8 months he had been irradiated for an inoperable intrathoracic neuroblastoma, and at the time of exposure to measles he was being treated with cyclophosphamide and vincristine. This case closely resembles other cases recently described and termed immunosuppressive measles encephalopathy. The syndrome is believed to represent the effect of measles virus in patients with deficient cellular immunity induced by antineoplastic treatment. The importance of protecting children on immunosuppressive treatment for contracting measles is stressed.

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

    PubMed

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

    2014-07-01

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

  20. FT-IR Study On Calcium Ion Binding To Bilirubin

    NASA Astrophysics Data System (ADS)

    Wu, Jin-Guang; Soloway, Roger D.; Xu, Duan-Fu; Wang, Xiu-Zhen; Martini, D. K.; Wagner, A. J.

    1989-12-01

    After formation of either the acid or neutral salt of calcium bilirubinate, decrease or disappearance of bands indicated that calcium is coordinated to bilirubin via its carboxyl oxygens and pyrrole nitrogens, changing the conjugated structure of the molecule.

  1. Management of Covert Hepatic Encephalopathy

    PubMed Central

    Waghray, Abhijeet; Waghray, Nisheet; Mullen, Kevin

    2015-01-01

    Hepatic encephalopathy is a reversible progressive neuropsychiatric disorder that encompasses a wide clinical spectrum. Covert hepatic encephalopathy is defined as patients with minimal hepatic encephalopathy and Grade I encephalopathy by West-Haven Criteria. Terminology such as “sub-clinical”, “latent”, and “minimal” appear to trivialize the disease and have been replaced by the term covert. The lack of clinical signs means that covert hepatic encephalopathy is rarely recognized or treated outside of clinical trials with options for therapy based on patients with episodic hepatic encephalopathy. This review discusses the current available options for therapy in covert hepatic encephalopathy and focuses on non-absorbable disacharides (lactulose or lactitol), antibiotics (rifaximin), probiotics/synbiotics and l-ornithine-l-aspartate. PMID:26041963

  2. Can Excess Bilirubin Levels Cause Learning Difficulties?

    ERIC Educational Resources Information Center

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

    2002-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  4. [Bovine spongiform encephalopathy].

    PubMed

    Suárez Fernández, G

    2001-01-01

    An histórical and conceptual review is made about Bovine Spongiform Encephalopathy or mad cows disease and an epidemiological analysis as a present and future health problem. This analysis of BSE should not be negative, considering the truths that we know today. PMID:11783042

  5. Effects of N-Acetylcysteine on Cytokines in Non-Acetaminophen Acute Liver Failure: Potential Mechanism of Improvement in Transplant-Free Survival

    PubMed Central

    Stravitz, R. Todd; Sanyal, Arun J.; Reisch, Joan; Bajaj, Jasmohan S.; Mirshahi, Faridoddin; Cheng, Jianfeng; Lee, William M.

    2016-01-01

    Background N-Acetylcysteine (NAC) improves transplant-free survival in patients with non-acetaminophen acute liver failure (ALF) when administered in early stages of hepatic encephalopathy. The mechanisms of this benefit are unknown. Aim To determine whether NAC improves transplant-free survival in ALF by ameliorating the surge of pro-inflammatory cytokines. Methods Serum samples were obtained from 78 participants of the randomized, ALF Study Group NAC Trial with grade 1 or 2 hepatic encephalopathy on randomization. Concentrations of ten cytokines, chosen to represent a wide array of inflammatory responses, were determined by multiplex ELISA. Results In univariate analysis, predictors of transplant-free survival included NAC administration (P=0.012), admission bilirubin (P=0.003), INR (P=0.0002), grade 1 vs. grade 2 encephalopathy (P=0.006) and lower admission interleukin (IL)-17 concentrations (P=0.011). IL-17 levels were higher in patients with grade 2 vs. 1 encephalopathy on randomization (P=0.007) and in those who progressed to grade 3 or 4 encephalopathy over the following 7 days (P≤0.01). Stepwise multivariate logistic regression analysis identified only NAC administration and lower IL-17 concentrations as independent predictors of transplant-free survival. In patients with detectable IL-17 concentrations on admission, 78% of those who received NAC vs. 44% of those who received placebo had undetectable levels by day 3-5 (P=0.042), and the mean decrease in IL-17 concentrations between admission and late samples was significantly greater in patients who received NAC vs. placebo (P=0.045). Conclusions NAC may improve transplant-free survival in patients with non-acetaminophen ALF by ameliorating the production of IL-17, which is associated with progression of hepatic encephalopathy and poor outcome. PMID:23782487

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

    SciTech Connect

    Vanstapel, F.; Blanckaert, N.

    1987-09-22

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

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

    PubMed Central

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

    2016-01-01

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

  8. KCNQ2 encephalopathy

    PubMed Central

    Millichap, John J.; Park, Kristen L.; Tsuchida, Tammy; Ben-Zeev, Bruria; Carmant, Lionel; Flamini, Robert; Joshi, Nishtha; Levisohn, Paul M.; Marsh, Eric; Nangia, Srishti; Narayanan, Vinodh; Ortiz-Gonzalez, Xilma R.; Patterson, Marc C.; Pearl, Phillip L.; Porter, Brenda; Ramsey, Keri; McGinnis, Emily L.; Taglialatela, Maurizio; Tracy, Molly; Tran, Baouyen; Venkatesan, Charu; Weckhuysen, Sarah

    2016-01-01

    Objective: To advance the understanding of KCNQ2 encephalopathy genotype–phenotype relationships and to begin to assess the potential of selective KCNQ channel openers as targeted treatments. Methods: We retrospectively studied 23 patients with KCNQ2 encephalopathy, including 11 treated with ezogabine (EZO). We analyzed the genotype–phenotype relationships in these and 70 previously described patients. Results: The mean seizure onset age was 1.8 ± 1.6 (SD) days. Of the 20 EEGs obtained within a week of birth, 11 showed burst suppression. When new seizure types appeared in infancy (15 patients), the most common were epileptic spasms (n = 8). At last follow-up, seizures persisted in 9 patients. Development was delayed in all, severely in 14. The KCNQ2 variants identified introduced amino acid missense changes or, in one instance, a single residue deletion. They were clustered in 4 protein subdomains predicted to poison tetrameric channel functions. EZO use (assessed by the treating physicians and parents) was associated with improvement in seizures and/or development in 3 of the 4 treated before 6 months of age, and 2 of the 7 treated later; no serious side effects were observed. Conclusions: KCNQ2 variants cause neonatal-onset epileptic encephalopathy of widely varying severity. Pathogenic variants in epileptic encephalopathy are clustered in “hot spots” known to be critical for channel activity. For variants causing KCNQ2 channel loss of function, EZO appeared well tolerated and potentially beneficial against refractory seizures when started early. Larger, prospective studies are needed to enable better definition of prognostic categories and more robust testing of novel interventions. Classification of evidence: This study provides Class IV evidence that EZO is effective for refractory seizures in patients with epilepsy due to KCNQ2 encephalopathy.

  9. KCNQ2 encephalopathy

    PubMed Central

    Millichap, John J.; Park, Kristen L.; Tsuchida, Tammy; Ben-Zeev, Bruria; Carmant, Lionel; Flamini, Robert; Joshi, Nishtha; Levisohn, Paul M.; Marsh, Eric; Nangia, Srishti; Narayanan, Vinodh; Ortiz-Gonzalez, Xilma R.; Patterson, Marc C.; Pearl, Phillip L.; Porter, Brenda; Ramsey, Keri; McGinnis, Emily L.; Taglialatela, Maurizio; Tracy, Molly; Tran, Baouyen; Venkatesan, Charu; Weckhuysen, Sarah

    2016-01-01

    Objective: To advance the understanding of KCNQ2 encephalopathy genotype–phenotype relationships and to begin to assess the potential of selective KCNQ channel openers as targeted treatments. Methods: We retrospectively studied 23 patients with KCNQ2 encephalopathy, including 11 treated with ezogabine (EZO). We analyzed the genotype–phenotype relationships in these and 70 previously described patients. Results: The mean seizure onset age was 1.8 ± 1.6 (SD) days. Of the 20 EEGs obtained within a week of birth, 11 showed burst suppression. When new seizure types appeared in infancy (15 patients), the most common were epileptic spasms (n = 8). At last follow-up, seizures persisted in 9 patients. Development was delayed in all, severely in 14. The KCNQ2 variants identified introduced amino acid missense changes or, in one instance, a single residue deletion. They were clustered in 4 protein subdomains predicted to poison tetrameric channel functions. EZO use (assessed by the treating physicians and parents) was associated with improvement in seizures and/or development in 3 of the 4 treated before 6 months of age, and 2 of the 7 treated later; no serious side effects were observed. Conclusions: KCNQ2 variants cause neonatal-onset epileptic encephalopathy of widely varying severity. Pathogenic variants in epileptic encephalopathy are clustered in “hot spots” known to be critical for channel activity. For variants causing KCNQ2 channel loss of function, EZO appeared well tolerated and potentially beneficial against refractory seizures when started early. Larger, prospective studies are needed to enable better definition of prognostic categories and more robust testing of novel interventions. Classification of evidence: This study provides Class IV evidence that EZO is effective for refractory seizures in patients with epilepsy due to KCNQ2 encephalopathy. PMID:27602407

  10. A neurotoxic alcohol exposure paradigm does not induce hepatic encephalopathy.

    PubMed

    Hashimoto, Joel G; Wiren, Kristine M; Wilhelm, Clare J

    2016-01-01

    Alcohol abuse is associated with neurological dysfunction, brain morphological deficits and frank neurotoxicity. Although these disruptions may be a secondary effect due to hepatic encephalopathy, no clear evidence of causality is available. This study examined whether a 72h period of alcohol intoxication known to induce physical dependence, followed by a single withdrawal, was sufficient to induce signs of hepatic encephalopathy in male and female mice. Animals were continuously intoxicated via alcohol vapor inhalation, a procedure previously shown to induce significant neurotoxicity in female mice. At peak synchronized withdrawal (8h following the end of alcohol exposure), blood samples were taken and levels of several liver-regulated markers and brain swelling were characterized. Glutathione levels were also determined in the medial frontal cortex (mFC) and hippocampus. Results revealed elevated levels of cholesterol, albumin, alkaline phosphatase (ALP), alanine aminotransferase (ALT) and decreased levels of blood urea nitrogen and total bilirubin in alcohol-exposed male and female groups compared to controls. Brain water weight was not affected by alcohol exposure, though males tended to have slightly more water weight overall. Alcohol exposure led to reductions in tissue levels of glutathione in both the hippocampus and mFC which may indicate increased oxidative stress. Combined, these results suggest that hepatic encephalopathy does not appear to play a significant role in the neurotoxicity observed following alcohol exposure in this model. PMID:27268733

  11. UDP-glucuronosyltransferase activity and bilirubin conjugation in the bullfrog.

    PubMed Central

    Cole, K D; Little, G H

    1983-01-01

    Bile pigments of bile and serum of Rana catesbeiana were investigated by means of high-pressure liquid chromatography. The major pigment in both bile and serum was bilirubin IX alpha. Bilirubin UDP-glucuronosyltransferase activity was found in the livers of all animals examined, but no conjugated bilirubin was detectable in the bile. Frog bile was found to contain large amounts of beta-glucuronidase. When the beta-glucuronidase inhibitor saccharo-1,4-lactone was introduced into the gall bladder followed by an exogenous bilirubin load, bilirubin glucuronide appeared in the bile. PMID:6411065

  12. Pharmacoeconomics of hepatic encephalopathy.

    PubMed

    Neff, Guy

    2010-05-01

    Understanding and appreciating the science of pharmacoeconomics have become even more important for health care providers and insurers during the recent economic downturn. Evaluating the true costs of any disease is complex; both direct costs, such as costs of drug therapy and the provision of care, and indirect costs, such as lost earnings and reduced quality of life, must be taken into account. With chronic liver disease, the most recent data indicate that direct costs were more than $2 billion whereas indirect costs were more than $450 million. Hepatic encephalopathy, a common complication of chronic liver disease, contributes to this economic burden. Although patients' length of stay during hospitalization for hepatic encephalopathy decreased from almost 9 days to 6 days (and has remained stable over the past few years) from 1993 to 2007, hospitalization costs rose from $13,000 to $30,000/hospital stay. In addition, 22% of patients were discharged directly to nursing homes or rehabilitation centers, which increases total costs. When assessing therapy for hepatic encephalopathy, it is important to consider the total costs of the disease, not just treatment costs. Although more expensive on a daily basis than lactulose, rifaximin has been shown to reduce hospitalization rates, has a better adverse-effect profile, and increases patient compliance. One study found that rifaximin produced a cost savings/patient/year of more than $3000 over lactulose therapy. PMID:20412038

  13. [Star fruit (Averrhoa carambola) toxic encephalopathy].

    PubMed

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

    2009-03-01

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

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

    SciTech Connect

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

    1988-07-01

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

  15. Conjugated and unconjugated bilirubins in bile of humans and rhesus monkeys. Structure of adult human and rhesus-monkey bilirubins compared with dog bilirubins.

    PubMed Central

    Blumenthal, S G; Taggart, D B; Ikeda, R; Ruebner, B; Bergstrom, D E

    1977-01-01

    1. Bilirubin-IXalpha, -IXalpha diglucuronide, -IXalpha monoglucuronide, -IXalpha monoglucoside -IXalpha monoxyloside, a bilirubin-IXalpha diconjugate containing glucose and another unknown compound, and bilirubin-IXbeta are present in gall-bladder bile of adult human, rhesus monkey and dog. Dog bile normally also contains other bilirubin-IXalpha diconjugates, i.e. compounds containing two conjugating sugars such as glucuronic acid and glucose, glucuronic acid and xylose and glucose xylose. 2. Azopigments alphaF, alphaO, alpha2, alpha3, betax and delta derived from human and rhesus-monkey bilirubins are identical in their chemical composition with those obtained from the dog. 3. Azopigments alphaF and betax found in diazotized biles of adult humans, rhesus monkeys and dogs are products of unconjugated bilirubin-IXbeta. 4. Technical modifications of previously published procedures [Heirwegh, Fevery, Michiels, Van Hees & Compernolle, (1975) Biochem. J. 145, 185-199] were introduced which make it possible to separate the bilirubins, diazotize the separated bilirubins, extract the azopigments and chromatograph them in one working day (6-8h). Images Fig. 1. Fig. 2. PMID:414741

  16. Toxic encephalopathy induced by capecitabine.

    PubMed

    Niemann, B; Rochlitz, C; Herrmann, R; Pless, M

    2004-01-01

    Toxic encephalopathy is a rarely described side effect of 5-fluorouracil which usually presents with cerebellar, neuropsychiatric, and focal neurological symptoms. Magnetic resonance imaging findings are described as patchy white matter alterations. We report the 1st case of capecitabine-induced toxic encephalopathy with epilepsy-like symptoms and diffuse white matter alterations on magnetic resonance imaging.

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

    PubMed

    Babin, Steven M; Sova, Raymond M

    2014-01-01

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

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

    PubMed Central

    Babin, Steven M; Sova, Raymond M

    2014-01-01

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

  19. Diets in Encephalopathy.

    PubMed

    Abdelsayed, George G

    2015-08-01

    As many as 80% of patients with end-stage liver disease and hepatic encephalopathy have significant protein-calorie malnutrition. Because of the severe hypercatabolic state of cirrhosis, the provision of liberal amounts of carbohydrate (at least 35 to 40 kcal/kg per day), and between 1.2 and 1.6 g/kg of protein is necessary. Protein restriction is not recommended. Branched-chain amino acid supplementation and vegetable protein are associated with improved outcomes. Dietary supplementation with vitamins, minerals (with the notable exception of zinc) and probiotics should be decided on a case-by-case basis. PMID:26195204

  20. Seeing more clearly through the fog of encephalopathy.

    PubMed

    Kaplan, Peter W; Sutter, Raoul

    2013-10-01

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

  1. Chirality inversion in the bilirubin molecular exciton.

    PubMed

    Boiadjiev, S E; Lightner, D A

    2001-05-15

    The bichromophoric pigment bilirubin acts as a molecular exciton in its UV-visible and circular dichroism (CD) spectroscopy. In both polar and nonpolar solvents, an optically active analog, (beta R,beta 'R)-dimethylmesobilirubin-XIII alpha (1), exhibits intense bisignate CD Cotton effects in the region of its long wavelength UV-vis absorption near 400 nm: Delta epsilon(434)(max) + 337, Delta epsilon(389)(max) - 186 (CHCl(3)), and Delta epsilon(431)(max) + 285, Delta epsilon(386)(max) - 177 (CH(3)OH). However, introduction of an amine into a CHCl(3) solution of 1 causes the Cotton effect signs to become inverted, e.g., after addition of NH(3), Delta epsilon(433)(max) - 345, Delta epsilon(389)(max) + 243, and after addition of ethylene diamine, Delta epsilon(435)(max) - 420, Delta epsilon(390)(max) + 299. The sign inversions imply inversion of molecular chirality of the bilirubin and the phenomenon appears to be general for amines, including alpha,omega-diamines. 1,8-Diaminooctane was found to be more effective than longer or shorter chain analogs in producing CD sign inversion.

  2. A Rare Complication Developing After Hematopoietic Stem Cell Transplantation: Wernicke’s Encephalopathy

    PubMed Central

    Solmaz, Soner; Gereklioğlu, Çiğdem; Tan, Meliha; Demir, Şenay; Yeral, Mahmut; Korur, Aslı; Boğa, Can; Özdoğu, Hakan

    2015-01-01

    Thiamine is a water-soluble vitamin. Thiamine deficiency can present as a central nervous system disorder known as Wernicke’s encephalopathy, which classically manifests as confusion, ataxia, and ophthalmoplegia. Wernicke’s encephalopathy has rarely been reported following hematopoietic stem cell transplantation. Herein, we report Wernicke’s encephalopathy in a patient with acute myeloid leukemia who had been receiving prolonged total parenteral nutrition after haploidentical allogeneic hematopoietic stem cell transplantation. To the best of our knowledge, this is the first case reported from Turkey in the literature. PMID:25912759

  3. Weak chemiluminescence of bilirubin and its stimulation by aldehydes.

    PubMed

    Watanabe, H; Usa, M; Kobayashi, M; Agatsuma, S; Inaba, H

    1992-01-01

    Bilirubin in an alkaline solution exhibits a weak chemiluminescence (CL) under aerobic conditions. This spontaneous CL was markedly enhanced by the addition of various aldehydes. The fluorescent emission spectrum of bilirubin, excited by weak intensity light at 350 nm, coincided with its CL emission spectrum (peak at 670 nm). CL emission from bilirubin was not quenched by active oxygen scavengers. This suggests that triplet oxygen reacts with bilirubin, and forms an oxygenated intermediate (hydroperoxide) as a primary emitter (oxidative scission of tetrapyrrole bonds in bilirubin is not involved in this CL). The Ehrlich reaction (test for monopyrroles) and hydrolsulphite reaction (test for dipyrroles) on the CL reaction mixture and unreacted bilirubin showed no differences. When the CL was initiated by singlet oxygen, rather than superoxide anion, monopyrrole, was detected in the reaction products by gel chromatography. The inhibitory effect of a scavenger of singlet oxygen on CL was eliminated in the presence of formaldehyde. Therefore, triplet carbonyl, formed by singlet oxygen through the dioxetane structure in bilirubin, is not an emitter. The reaction mechanism of bilirubin CL and the formation of a hydroperoxide intermediate is discussed in relation to the chemical structure of luciferin molecules from bioluminescent organisms.

  4. Induction of bilirubin clearance by the constitutive androstane receptor (CAR).

    PubMed

    Huang, Wendong; Zhang, Jun; Chua, Steven S; Qatanani, Mohammed; Han, Yunqing; Granata, Riccarda; Moore, David D

    2003-04-01

    Bilirubin clearance is one of the numerous important functions of the liver. Defects in this process result in jaundice, which is particularly common in neonates. Elevated bilirubin levels can be decreased by treatment with phenobarbital. Because the nuclear hormone receptor constitutive androstane receptor (CAR) mediates hepatic effects of this xenobiotic inducer, we hypothesized that CAR could be a regulator of bilirubin clearance. Activation of the nuclear hormone receptor CAR increases hepatic expression of each of five components of the bilirubin-clearance pathway. This induction is absent in homozygous CAR null mice but is observed in mice expressing human CAR instead of mouse CAR. Pretreatment with xenobiotic inducers markedly increases the rate of clearance of an exogenous bilirubin load in wild-type but not CAR knockout animals. Bilirubin itself can also activate CAR, and mice lacking CAR are defective in clearing chronically elevated bilirubin levels. Unexpectedly, CAR expression is very low in livers of neonatal mice and humans. We conclude that CAR directs a protective response to elevated bilirubin levels and suggest that a functional deficit of CAR activity may contribute to neonatal jaundice. PMID:12644704

  5. Hepatic encephalopathy: historical remarks.

    PubMed

    Amodio, Piero

    2015-03-01

    The history of hepatic encephalopathy (HE) is briefly reviewed since the beginning of western medicine by Hippocrates. For about 2000 years the main evidence was the mere association between jaundice, fever and delirium. A clear link between delirium and cirrhosis was proven in the 17th century by Morgagni. In subsequent times the focus was manly the descriptions of symptoms and the only pathophysiological improvement was the evidence that jaundice, per se, does not alter brain function. Only at the end of the 19th century Hann et al proved the role of portal-systemic shunt and pf nitrogenous derivates in the pathophysiology of the syndrome. A terrific development of knowledge occurred in the last 60 years, after the works of Sherlock in London. Nowadays some consensus about HE was reached, so that new developments will likely occur. PMID:26041956

  6. [Bromide encephalopathies (author's transl)].

    PubMed

    Loubrieu, G; Bourin, M; Bizière, K; Breteau, M; Autret, A

    1979-07-01

    Bromide encephalopathies are frequently reported in Northern America and Great Britain. There is no characteristic clinical pattern, the neurological symptoms are multiple, this is readily explained by the diffusion of bromide ions to all regions in the central nervous system. An accurate history (bromide intake, followed by the slow onset of digestive and neuropsychiatric symptoms) as well as an apparent hyperchloremia are of the greatest aid in suggesting the diagnosis. The incidence of this type of intoxication is greater in women over 50. The association of a salt free diet to bromide therapy favors the onset of clinical symptoms because of the competition between bromide and chloride at the choroid plexus and at the renal tubule.

  7. [Prevention of hepatic encephalopathy].

    PubMed

    Morillas, Rosa M; Sala, Marga; Planas, Ramon

    2014-06-01

    Hepatic encephalopathy (HE) is a frequent complication of cirrhosis which, in addition to producing a great social impact, deteriorates the quality of life of patients and is considered a sign of advanced liver disease and therefore a clinical indication for liver transplant evaluation. Patients who have had episodes of HE have a high risk of recurrence. Thus, after the HE episode resolves, it is recommended: control and prevention of precipitating factors (gastrointestinal bleeding, spontaneous bacterial peritonitis, use of diuretics with caution, avoid nervous system depressant medications), continued administration of non-absorbable disaccharides such as lactulose or lactitol, few or non-absorbable antibiotics such as rifaximin and assess the need for a liver transplant as the presence of a HE episode carries a poor prognosis in cirrhosis.

  8. Conjugated Bilirubin Triggers Anemia by Inducing Erythrocyte Death

    PubMed Central

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

    2015-01-01

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

  9. Enzymatic polymerization of dihydroquercetin using bilirubin oxidase.

    PubMed

    Khlupova, M E; Vasil'eva, I S; Shumakovich, G P; Morozova, O V; Chertkov, V A; Shestakova, A K; Kisin, A V; Yaropolov, A I

    2015-02-01

    Dihydroquercetin (or taxifolin) is one of the most famous flavonoids and is abundant in Siberian larch (Larix sibirica). The oxidative polymerization of dihydroquercetin (DHQ) using bilirubin oxidase as a biocatalyst was investigated and some physicochemical properties of the products were studied. DHQ oligomers (oligoDHQ) with molecular mass of 2800 and polydispersity of 8.6 were obtained by enzymatic reaction under optimal conditions. The oligomers appeared to be soluble in dimethylsulfoxide, dimethylformamide, and methanol. UV-visible spectra of oligoDHQ in dimethylsulfoxide indicated the presence of highly conjugated bonds. The synthesized oligoDHQ was also characterized by FTIR and (1)H and (13)C NMR spectroscopy. Comparison of NMR spectra of oligoDHQ with DHQ monomer and the parent flavonoids revealed irregular structure of a polymer formed via the enzymatic oxidation of DHQ followed by nonselective radical polymerization. As compared with the monomer, oligoDHQ demonstrated higher thermal stability and high antioxidant activity.

  10. STEC:O111-HUS complicated by acute encephalopathy in a young girl was successfully treated with a set of hemodiafiltration, steroid pulse, and soluble thrombomodulin under plasma exchange.

    PubMed

    Yada, Noritaka; Fujioka, Masayuki; Bennett, Charles L; Inoki, Kazuya; Miki, Toyokazu; Watanabe, Akihiko; Yoshida, Toshiko; Hayakawa, Masaki; Matsumoto, Masanori; Fujimura, Yoshihiro

    2015-04-01

    We report a 14-year-old girl, who developed shigatoxin-producing E. coli (STEC)-HUS complicated by encephalopathy. She was successfully treated with hemodiafiltration, high-dose methylprednisolone pulse therapy, and soluble recombinant thrombomodulin under plasma exchange. von Willebrand factor multimers analysis provides potential insights into how the administered therapies might facilitate successful treatment of STEC-HUS.

  11. Brainstem variant of posterior reversible encephalopathy syndrome: A case report.

    PubMed

    Tortora, Fabio; Caranci, Ferdinando; Belfiore, Maria Paola; Manzi, Francesca; Pagliano, Pasquale; Cirillo, Sossio

    2015-12-01

    Posterior reversible encephalopathy syndrome (PRES) is a clinico-radiological condition, generally observed in conjunction with severe and acute hypertension, that involves mainly the posterior head areas (occipital and temporal lobes) and anterior "watershed" areas. In this syndrome it is rare to observe a predominant involvement of the brainstem. We describe the clinical and radiological findings in a patient with brainstem involvement, discussing its pathophysiological features and possible differential diagnosis.

  12. Subcortical arteriosclerotic encephalopathy: a clinical and radiological investigation.

    PubMed Central

    Loizou, L A; Kendall, B E; Marshall, J

    1981-01-01

    Subcortical arteriosclerotic encephalopathy (Binswanger's type) was diagnosed in a group of patients with hypertension or arteriosclerosis, who showed acute and subacute neurological deficits, dementia, reduced cerebral blood flow, and white matter low attenuation with mild atrophy and infarcts as the predominant CT scan features. This set of clinical and radiological criteria could be used to make the diagnosis in life, as confirmed neuropathologically in one patient. Images PMID:7241156

  13. Association of abnormal plasma bilirubin with aggressive HCC phenotype

    PubMed Central

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

    2014-01-01

    Background Cirrhosis-related abnormal liver function is associated with predisposition to HCC, features in several HCC classification systems and is an HCC prognostic factor. Aims To examine the phenotypic tumor differences in HCC patients with normal or abnormal plasma bilirubin levels. Methods A 2,416 patient HCC cohort was studied and dichotomized into normal and abnormal plasma bilirubin groups. Their HCC characteristics were compared for tumor aggressiveness features, namely blood AFP levels, tumor size, presence of PVT and tumor multifocality. Results In the total cohort, elevated bilirubin levels were associated with higher AFP levels, increased PVT and multifocality and lower survival, despite similar tumor sizes. When different tumor size terciles were compared, similar results were found, even for small tumor size patients. A multiple logistic regression model for PVT or tumor multifocality showed increased OddsRatios for elevated levels of GGTP, bilirubin and AFP and for larger tumor sizes. Conclusions HCC patients with abnormal bilirubin levels had worse prognosis than patients with normal bilirubin. They also had increased incidence of PVT and tumor multifocality and higher AFP levels, in patients with both small and larger tumors. The results show an association between bilirubin levels and indices of HCC aggressiveness. PMID:24787296

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

    PubMed

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

    2014-04-01

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

  15. Influence of assessment site in measuring transcutaneous bilirubin

    PubMed Central

    da Conceição, Cristiane Maria; Dornaus, Maria Fernanda Pellegrino da Silva; Portella, Maria Aparecida; Deutsch, Alice D'Agostini; Rebello, Celso Moura

    2014-01-01

    ABSTRACT Objective: To investigate the influence of the site of measurement of transcutaneous bilirubin (forehead or sternum) in reproducibility of results as compared to plasma bilirubin. Methods: A cohort study including 58 term newborns with no hemolytic disease. Transcutaneous measurements were performed on the forehead (halfway between the headline and the glabella, from the left toward the right side, making consecutive determinations, one-centimeter apart) and the sternum (five measurements, from the suprasternal notch to the xiphoid process with consecutive determinations, one-centimeter apart) using Bilicheck® (SpectRx Inc, Norcross, Georgia, USA). The correlation and agreement between both methods and plasma bilirubin were calculated. Results: There was a strong linear correlation between both determinations of serum bilirubin at the forehead and sternum (r=0.704; p<0.01 and r=0.653; p<0.01, respectively). There was correspondence of the mean values of transcutaneous bilirubin measured on the sternum (9.9±2.2mg/dL) compared to plasma levels (10.2±1.7mg/dL), but both differ from the values measured on the forehead (8.6±2.0mg/dL), p<0.05. Conclusion: In newborn term infants with no hemolytic disease, measuring of transcutaneous bilirubin on the sternum had higher accuracy as compared to serum bilirubin measurement on the forehead. PMID:24728239

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

    PubMed

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

    2014-04-01

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

  17. The transmissible spongiform encephalopathies of livestock

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Prion diseases or transmissible spongiform encephalopathies (TSEs) are fatal protein misfolding neurodegenerative diseases. TSEs have been described in several species including bovine spongiform encephalopathy (BSE) in cattle, scrapie in sheep and goats, chronic wasting disease (CWD) in cervids, tr...

  18. Sepsis-Associated Encephalopathy

    PubMed Central

    Cotena, Simona; Piazza, Ornella

    2012-01-01

    Summary Sepsis-associated encephalopathy (SAE) is defined as a diffuse or multifocal cerebral dysfunction induced by the systemic response to the infection without clinical or laboratory evidence of direct brain infection. Its pathogenesis is multifactorial. SAE generally occurs early during severe sepsis and precedes multiple-organ failure. The most common clinical feature of SAE is the consciousness alteration which ranges from mildly reduced awareness to unresponsiveness and coma. Diagnosis of SAE is primarily clinical and depends on the exclusion of other possible causes of brain deterioration. Electroencephalography (EEG) is almost sensitive, but it is not specific for SAE. Computed Tomography (CT) head scan generally is negative in case of SAE, while Magnetic Resonance Imaging (MRI) can show brain abnormalities in case of SAE, but they are not specific for this condition. Somatosensitive Evoked Potentials (SEPs) are sensitive markers of developing cerebral dysfunction in sepsis. Cerebrospinal fluid (CBF) analysis is generally normal, a part an inconstant elevation of proteins concentration. S100B and NSE have been proposed like biomarkers for diagnosis of SAE, but the existing data are controversial. SAE is reversible even if survivors of severe sepsis have often long lasting or irreversible cognitive and behavioral sequel; however the presence of SAE can have a negative influence on survival. A specific therapy of SAE does not exist and the outcome depends on a prompt and appropriate treatment of sepsis as whole. PMID:23905041

  19. Chronic traumatic encephalopathy.

    PubMed

    Yi, Juneyoung; Padalino, David J; Chin, Lawrence S; Montenegro, Philip; Cantu, Robert C

    2013-01-01

    Sports-related concussion has gained increased prominence, in part due to media coverage of several well-known athletes who have died from consequences of chronic traumatic encephalopathy (CTE). CTE was first described by Martland in 1928 as a syndrome seen in boxers who had experienced significant head trauma from repeated blows. The classic symptoms of impaired cognition, mood, behavior, and motor skills also have been reported in professional football players, and in 2005, the histopathological findings of CTE were first reported in a former National Football League (NFL) player. These finding were similar to Alzheimer's disease in some ways but differed in critical areas such as a predominance of tau protein deposition over amyloid. The pathophysiology is still unknown but involves a history of repeated concussive and subconcussive blows and then a lag period before CTE symptoms become evident. The involvement of excitotoxic amino acids and abnormal microglial activation remain speculative. Early identification and prevention of this disease by reducing repeated blows to the head has become a critical focus of current research.

  20. [Mitochondrial neurogastrointestinal encephalopathy disease].

    PubMed

    Benureau, A; Meyer, P; Maillet, O; Leboucq, N; Legras, S; Jeziorski, E; Fournier-Favre, S; Jeandel, C; Gaignard, P; Slama, A; Rivier, F; Roubertie, A; Carneiro, M

    2014-12-01

    Mitochondrial neurogastrointestinal encephalopathy disease (MNGIE) is a rare autosomal-recessive syndrome, resulting from mutations in the TYMP gene, located at 22q13. The mutation induces a thymidine phosphorylase (TP) deficit, which leads to a nucleotide pool imbalance and to instability of the mitochondrial DNA. The clinical picture regroups gastrointestinal dysmotility, cachexia, ptosis, ophthalmoplegia, peripheral neuropathy, and asymptomatic leukoencephalopathy. The prognosis is unfavorable. We present the case of a 14-year-old Caucasian female whose symptoms started in early childhood. The diagnosis was suspected after magnetic resonance imaging (MRI), performed given the atypical features of mental anorexia, which revealed white matter abnormalities. She presented chronic vomiting, postprandial abdominal pain, and problems gaining weight accompanied by cachexia. This diagnosis led to establishing proper care, in particular an enteral and parenteral nutrition program. There is no known specific effective treatment, but numerous studies are in progress. In this article, after reviewing the existing studies, we discuss the main diagnostic and therapeutic aspects of the disease. We argue for the necessity of performing a cerebral MRI given the atypical features of a patient with suspected mental anorexia (or when the clinical pattern of a patient with mental anorexia seems atypical), so that MNGIE can be ruled out. PMID:25282463

  1. Sepsis-associated encephalopathy.

    PubMed

    Gofton, Teneille E; Young, G Bryan

    2012-10-01

    Sepsis-associated encephalopathy (SAE) is a diffuse brain dysfunction that occurs secondary to infection in the body without overt CNS infection. SAE is frequently encountered in critically ill patients in intensive care units, and in up to 70% of patients with severe systemic infection. The severity of SAE can range from mild delirium to deep coma. Seizures and myoclonus are infrequent and cranial nerves are almost always spared, but most severe cases have an associated critical illness neuromyopathy. Development of SAE probably involves a number of mechanisms that are not mutually exclusive and vary from patient to patient. Substantial neurological and psychological morbidities often occur in survivors. Mortality is almost always due to multiorgan failure rather than neurological complications, and is almost 70% in patients with severe SAE. Further research into the pathophysiology, management and prevention of SAE is needed. This Review discusses the epidemiology and clinical presentation of SAE. Recent evidence for SAE pathophysiology is outlined and a diagnostic approach to patients with this syndrome is presented. Lastly, prognosis and management of SAE is discussed.

  2. Sepsis Associated Encephalopathy.

    PubMed

    Chaudhry, Neera; Duggal, Ashish Kumar

    2014-01-01

    Sepsis associated encephalopathy (SAE) is a common but poorly understood neurological complication of sepsis. It is characterized by diffuse brain dysfunction secondary to infection elsewhere in the body without overt CNS infection. The pathophysiology of SAE is complex and multifactorial including a number of intertwined mechanisms such as vascular damage, endothelial activation, breakdown of the blood brain barrier, altered brain signaling, brain inflammation, and apoptosis. Clinical presentation of SAE may range from mild symptoms such as malaise and concentration deficits to deep coma. The evaluation of cognitive dysfunction is made difficult by the absence of any specific investigations or biomarkers and the common use of sedation in critically ill patients. SAE thus remains diagnosis of exclusion which can only be made after ruling out other causes of altered mentation in a febrile, critically ill patient by appropriate investigations. In spite of high mortality rate, management of SAE is limited to treatment of the underlying infection and symptomatic treatment for delirium and seizures. It is important to be aware of this condition because SAE may present in early stages of sepsis, even before the diagnostic criteria for sepsis can be met. This review discusses the diagnostic approach to patients with SAE along with its epidemiology, pathophysiology, clinical presentation, and differential diagnosis.

  3. [Wernicke's encephalopathy induced by the use of diet pills and unbalanced diet].

    PubMed

    Tóth, Adrián; Aradi, Gabriella; Várallyay, György; Arányi, Zsuzsanna; Bereczki, Dániel; Vastagh, Ildikó

    2014-03-23

    Wernicke's encephalopathy is an acute, potentially life-threatening, neurological syndrome resulting from thiamine deficiency. The disorder is still greatly underdiagnosed and, without prompt treatment, the condition can lead to the chronic form of the disease, Korsakoff's syndrome or even death. In developed countries Wernicke's encephalopathy has been associated with alcoholism, but in recent years there has been an increasing number of non-alcoholic cases. Authors report the case of a 23-year-old woman who developed oculomotor dysfunction, encephalopathy and ataxia as a result of an extreme diet and use of diet pills. The diagnosis of Wernicke's encephalopathy was supported by the resolution of neurological signs after parenteral thiamine replacement. This case is presented because of the rare etiology and diagnostic difficulty, and the latest diagnostic and therapic guidelines are also highlighted. PMID:24631935

  4. Approach to clinical syndrome of jaundice and encephalopathy in tropics.

    PubMed

    Anand, Anil C; Garg, Hitendra K

    2015-03-01

    A large number of patients present with jaundice and encephalopathy in tropical country like India and acute liver failure is the usual cause. Clinical presentation like ALF is also a complication of many tropical infections, and these conditions may mimic ALF but may have subtle differences from ALF. Moreover, what hepatologists see as acute liver failure in tropics is different from what is commonly described in Western Textbooks. Paracetamol overdose, which is possibly the commonest cause of ALF in UK and USA, is hardly ever seen in India. Most common etiology here is viral hepatitis (hepatitis E > hepatitis B> hepatitis A). Apart from ALF, one may also come across subacute hepatic failure (SAHF) as well as acute-on-chronic liver failure (ACLF) due to viral hepatitis. Interestingly, a host of other conditions can mimic ALF because clinical presentation in these conditions can be dominated by jaundice and encephalopathy. Malarial hepatopathy is possibly the best-known condition out of these and is not an uncommon manifestation of severe malaria. A similar presentation can also be seen in other common infections in tropics such as dengue fever, typhoid fever, leptospirosis, scrub typhus, amoebic liver abscesses, tuberculosis and other bacterial and fungal infections with or without human immunodeficiency virus (HIV) related disease. In many of these conditions, liver failure may not be underlying pathophysiology. Some pregnancy related liver diseases could also present with jaundice and encephalopathy. This review summarizes the commonly seen presentations in tropical country like India, where jaundice and encephalopathy dominate the clinical picture.

  5. Composition And Coordination Of Non-Stoichiometric Calcium Bilirubinate***

    NASA Astrophysics Data System (ADS)

    Yang, Zhanlan; Soloway, Roger D.; Weng, Shifu; Wang, Jiafu; Xu, Duan-Fu; Wu, Jin-Guang

    1989-12-01

    Since calcium bilirubinate (CaBR) and its acid salt (CaHBR) were considered to be the main components of human pigment gallstone, these compounds were synthesized and investigated chemically, crystallographically and spectroscopically by several authors. In recent years, we found that the chemical compositions of these compounds varied from sample to sample, and the protonated carboxyl group of these samples was much more reactive than for bilirubin. It resembles the characteristics of human pigment gallstone. In order to enhance our understanding of the structure of gallstone, an investigation on the composition and coordination of calcium bilirubinate has been carried out. A series of CaHBR samples were prepared by reacting diluted pyridine solutions of bilirubin and

  6. [Relationship of bilirubin to diseases caused by increased oxidative stress].

    PubMed

    Vítek, L

    2013-07-01

    Oxidative stress contributes importantly to pathogenesis of numerous civilization diseases, including cardiovascular diseases, cancer, as well as autoimmune and neurodegenerative conditions. Bilirubin is the major product of the heme catabolic pathway in the intravascular compartment. For long time, bilirubin was considered to be only a waste product, however, recent data from the last 2 decades have proved its important antioxidant properties, which contributes to defense against increased oxidative stress. Numerous experimental as well as clinical studies have demonstrated association between low bilirubin concentrations and cardiovascular diseases, diabetes, certain cancers, autoimunne diseases, such as lupus erythematodes, or rheumatoid arthritis or neurological psychiatric disorders, such as schizofrenia. On the other hand, subjects with mildly elevated blood bilirubin levels, typical for Gilbert syndrome, have decreased risk of these diseases. PMID:23909269

  7. STEC:O111-HUS complicated by acute encephalopathy in a young girl was successfully treated with a set of hemodiafiltration, steroid pulse, and soluble thrombomodulin under plasma exchange

    PubMed Central

    Yada, Noritaka; Fujioka, Masayuki; Bennett, Charles L; Inoki, Kazuya; Miki, Toyokazu; Watanabe, Akihiko; Yoshida, Toshiko; Hayakawa, Masaki; Matsumoto, Masanori; Fujimura, Yoshihiro

    2015-01-01

    Key Clinical Message We report a 14-year-old girl, who developed shigatoxin-producing E. coli (STEC)-HUS complicated by encephalopathy. She was successfully treated with hemodiafiltration, high-dose methylprednisolone pulse therapy, and soluble recombinant thrombomodulin under plasma exchange. von Willebrand factor multimers analysis provides potential insights into how the administered therapies might facilitate successful treatment of STEC-HUS. PMID:25914810

  8. Reversible encephalopathy associated with cholesterol embolism syndrome: magnetic resonance imaging and pathological findings

    PubMed Central

    Andreux, F; Marro, B; Khoury, N EI; Seilhean, D; Alamowitch, S

    2007-01-01

    We describe a patient found to have acute diffuse and reversible encephalopathy on magnetic resonance imaging (MRI) associated with cholesterol emboli syndrome (CES). The initial MRI showed extensive white matter, basal ganglia and cortical damage without evidence of brain infarction. Dramatic clinical and MRI improvement was observed with corticosteroids. Pathologically, cholesterol crystal emboli were found in the lumen of skin and brain arteries and were associated with varying degrees of inflammation of the arteriole wall. This case suggests that CES may be responsible for extensive, acute and reversible encephalopathy underlined by an inflammation of brain arteries. PMID:17229746

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

    PubMed

    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.

  10. [A new direct solubilizer for bilirubinate calcium stones].

    PubMed

    Asakawa, S; Igimi, H; Shimura, H

    1983-10-01

    Hepatobiliary surgeons must have faced difficulty in treating patients with intrahepatic gallstones. In spite of considerable progress in operative methods or mechanical techniques, it is very difficult to remove intrahepatic gallstones completely. Under such circumstances, the development of a solubilizer that can dissolve intrahepatic bilirubinate calcium stones by means of injecting it through a postoperative catheter or PTCD catheter has been awaited. Up to now, a chelating agent, so-called hexametaphosphate (HMP) has been used for removing the calcium from calcium bilirubinate. But this chelating agent, in itself, cannot dissolve the bilirubin. The authors found a direct solubilizer for bilirubin, dimethyl sulfoxide (DMSO) which is a well known bi-polar non protonic solvent and used as an accelerator for bilirubin determination. After the purification of DMSO to 99.98%, toxicity was examined by oral administration, intravenous administration and infusion into biliary tract. But no remarkable toxicity or side effects were detected on biochemical and pathological examinations. Clinical application of 90% DMSO together with 5% HMP was performed and a satisfactory effect was obtained as a direct solubilizer for bilirubinate calcium stones.

  11. Hashimoto's Encephalopathy Presenting with Chorea.

    PubMed

    Sharan, Abhijeet; Sengupta, Sarbani; Mukhopadhyay, Sarmishtha; Ghosh, Bhaskar

    2015-09-01

    Hashimoto's encephalopathy (HE) is a steroid-responsive relapsing neuropsychiatric disorder associated with high titers of antithyroid antibody with or without thyroid dysfunction. We report a case of HE in a 78 year old female who developed sudden onset behavioral abnormalities associated with choreiform movement of extremities. All causes of vascular, infective, metabolic, autoimmune, paraneoplastic and toxic encephalopathy were excluded. Anti-thyroid peroxidase (anti-TPO) antibody was found to be raised with very high titre. A diagnosis of HE was made. Prompt treatment with high dose steroid led to dramatic improvement of symptoms including choreiform movement. PMID:27608878

  12. The burden of hepatic encephalopathy in Latin America.

    PubMed

    Dávalos Moscol, Milagros; Bustios Sanchez, Carla

    2011-06-01

    Hepatic encephalopathy (HE) is a neuropsychiatric syndrome characterized by changes in cognitive function, behavior, and personality, as well as by transient neurological symptoms and electroencephalographic changes, which occur in the context of acute or chronic liver failure. Cirrhosis is the main disease associated to HE, and it is known that its incidence is increasing worldwide. As a cause of mortality, cirrhosis is ranked 14 worldwide, but 10 in developed countries. It has been demonstrated that the incidence of liver disease is increasing, in part because of the ascending prevalence of NAFLD, HCV, HCC, as well of alcohol consumption. The real incidence of cirrhosis in Latin America is unknown, although in some Latin American countries that provided national data, cirrhosis death rates were between 5 and 17/100,000 for men and 3 and 5/100,000 for women. Disability, quality of life, and social aspects should be considered when assessing the impact of a disease. In this context, preliminary estimates of the global burden of disease attributable to chronic liver disease seem to be substantial. Hepatic encephalopathy, a main complication of liver failure, occurs in 30-45% of patients as overt encephalopathy, but when subclinical or minimal hepatic encephalopathy (MHE) is considered, estimates of the incidence of encephalopathy vary from 20 to 60%. In USA, the 2009 NIH Report on the Costs of Digestive Diseases stated that liver disease was the second most costly disease in direct and indirect costs (13.1 billion dollars). Although the economic cost of HE has not been assessed, it is obvious that the economic impact of HE on daily activities of living is extremely high, as the costs of diminished work performance and lost wages are substantial.

  13. Profile of minocycline neuroprotection in bilirubin-induced auditory system dysfunction.

    PubMed

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

    2011-01-12

    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. This study evaluates the neuroprotective capabilities of minocycline HCl (50 mg/kg) administered 30 or 120 min after sulfa (200 mg/kg) in 16 days old jjs. BAEPs are recorded at 6 or 24 h post-sulfa. Abnormal BAEP waves exhibit increased latency and decreased amplitude. The sulfa/saline treated jjs exhibited a significantly increased interwave interval between waves I and II (I-II IWI) and significantly decreased amplitudes of waves II and III compared to the saline/saline jjs. The minocycline 30 min post-sulfa (sulfa/mino+30) group was not significantly different from the saline/saline control group, indicating neuroprotection. The minocycline 120 min post-sulfa (sulfa/mino+120) group had a significantly decreased amplitude of wave III at both 6 and 24h. These studies indicate that minocycline has a graded neuroprotective effect when administered after acute bilirubin neurotoxicity.

  14. Role of bilirubin oxidation products in the pathophysiology of DIND following SAH.

    PubMed

    Pyne-Geithman, Gail J; Nair, Sunil G; Stamper, Danielle N Caudell; Clark, Joseph F

    2013-01-01

    Despite intensive research efforts, by our own team and many others, the molecules responsible for acute neurological damage following subarachnoid hemorrhage (SAH) and contributing to delayed ischemic neurological deficit (DIND) have not yet been elucidated. While there are a number of candidate mechanisms, including nitric oxide (NO) scavenging, endothelin-1, protein kinase C (PKC) activation, and rho kinase activation, to name but a few, that have been investigated using animal models and human trials, we are, it seems, no closer to discovering the true nature of this complex and enigmatic pathology. Efforts in our laboratory have focused on the chemical milieu present in hemorrhagic cerebrospinal fluid (CSF) following SAH and the interaction of the environment with the molecules generated by SAH and subsequent events, including NO scavenging, immune response, and clot breakdown. We have identified and characterized a group of molecules formed by the oxidative degradation of bilirubin (a clot breakdown product) and known as BOXes (bilirubin oxidation products). We present a synopsis of the characterization of BOXes as found in human SAH patients' CSF and the multiple signaling pathways by which BOXes act. In summary, BOXes are likely to play an essential role in the etiology of acute brain injury following SAH, as well as DIND. PMID:22890679

  15. Contributions of Microdialysis to New Alternative Therapeutics for Hepatic Encephalopathy

    PubMed Central

    Rivera-Espinosa, Liliana; Floriano-Sánchez, Esaú; Pedraza-Chaverrí, José; Coballase-Urrutia, Elvia; Sampieri, Aristides; Ortega-Cuellar, Daniel; Cárdenas-Rodríguez, Noemí; Carmona-Aparicio, Liliana

    2013-01-01

    Hepatic encephalopathy (HE) is a common complication of cirrhosis, of largely reversible impairment of brain function occurring in patients with acute or chronic liver failure or when the liver is bypassed by portosystemic shunts. The mechanisms causing this brain dysfunction are still largely unclear. The need to avoid complications caused by late diagnosis has attracted interest to understand the mechanisms underlying neuronal damage in order to find markers that will allow timely diagnosis and to propose new therapeutic alternatives to improve the care of patients. One of the experimental approaches to study HE is microdialysis; this technique allows evaluation of different chemical substances in several organs through the recollection of samples in specific places by semi-permeable membranes. In this review we will discuss the contributions of microdialysis in the understanding of the physiological alterations in human hepatic encephalopathy and experimental models and the studies to find novel alternative therapies for this disease. PMID:23921686

  16. Contributions of microdialysis to new alternative therapeutics for hepatic encephalopathy.

    PubMed

    Rivera-Espinosa, Liliana; Floriano-Sánchez, Esaú; Pedraza-Chaverrí, José; Coballase-Urrutia, Elvia; Sampieri, Aristides Iii; Ortega-Cuellar, Daniel; Cárdenas-Rodríguez, Noemí; Carmona-Aparicio, Liliana

    2013-08-05

    Hepatic encephalopathy (HE) is a common complication of cirrhosis, of largely reversible impairment of brain function occurring in patients with acute or chronic liver failure or when the liver is bypassed by portosystemic shunts. The mechanisms causing this brain dysfunction are still largely unclear. The need to avoid complications caused by late diagnosis has attracted interest to understand the mechanisms underlying neuronal damage in order to find markers that will allow timely diagnosis and to propose new therapeutic alternatives to improve the care of patients. One of the experimental approaches to study HE is microdialysis; this technique allows evaluation of different chemical substances in several organs through the recollection of samples in specific places by semi-permeable membranes. In this review we will discuss the contributions of microdialysis in the understanding of the physiological alterations in human hepatic encephalopathy and experimental models and the studies to find novel alternative therapies for this disease.

  17. HEV infection as an aetiologic factor for acute hepatitis: experience from a tertiary hospital in Bangladesh.

    PubMed

    Mamun-Al-Mahtab; Rahman, Salimur; Khan, Mobin; Karim, Fazal

    2009-02-01

    Acute hepatitis is seen sporadically round the year in Bangladesh. The incidence of acute viral hepatitis E increases after floods as this allows sewerage contamination of piped and groundwater. The aim of this retrospective study was to assess the burden of hepatitis E virus (HEV infection) in Bangladesh. Patients attending the Hepatology Unit III of the Bangabandhu Sheikh Mujib Medical University, during June 2004-December 2006, were included in the study. All viral markers were tested by enzyme-linked immunosorbent assay. The study population was divided in four groups. Group 1 included 144 patients with acute viral hepatitis. The inclusion criteria were: nausea and/or vomiting, loss of appetite, serum bilirubin >200 micromol/L, raised serum transaminases, and prothrombin time >3 seconds prolonged beyond control value. In Group 2, there were 31 pregnant women with acute viral hepatitis. All the patients had prodrome, icterus, raised serum bilirubin and raised serum transaminase levels. Group 3 included 23 patients presenting with fulminant hepatic failure. In Group 4, 69 patients with cirrhosis of liver were included. They presented with features of decompensation for the first time. The inclusion criteria were: patients with established cirrhosis with jaundice and/or ascites and/or hepatic encephalopathy. In Group 1, 58.33% of the 144 patients had acute viral hepatitis E. In Group 2, 45.16% of the pregnant women also had acute viral hepatitis E. HEV was responsible for 56.52% cases of fulminant hepatic failure in Group 3. In 21.7% cases in Group 4, decompensation of cirrhosis was due to HEV. Acute viral hepatitis E in the third trimester of pregnancy and HEV-induced fulminant hepatic failure were associated with 80% of mortality despite the best possible care. In this clinical context, acute viral hepatitis E is the leading cause of wide spectrum of liver disease ranging from severe acute viral hepatitis, fulminant hepatic failure, to decompensation of liver in

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

    NASA Astrophysics Data System (ADS)

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

    2012-03-01

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

  19. Pharmacotherapy for hepatic encephalopathy.

    PubMed

    Phongsamran, Paula V; Kim, Jiwon W; Cupo Abbott, Jennifer; Rosenblatt, Angela

    2010-06-18

    Hepatic encephalopathy (HE) is a challenging clinical complication of liver dysfunction with a wide spectrum of neuropsychiatric abnormalities that range from mild disturbances in cognitive function and consciousness to coma and death. The pathogenesis of HE in cirrhosis is complex and multifactorial, but a key role is thought to be played by circulating gut-derived toxins of the nitrogenous compounds, most notably ammonia. Therapeutic treatment options for HE are currently limited and have appreciable risks and benefits associated with their use. Management of HE primarily involves avoidance of precipitating factors, limitation of dietary protein intake, and administration of various ammonia-lowering therapies such as non-absorbable disaccharides and select antimicrobial agents. Non-absorbable disaccharides, such as lactulose, have traditionally been regarded as first-line pharmacotherapy for patients with HE. However, multiple adverse events have been associated with their use. In addition, recent literature has questioned the true efficacy of the disaccharides for this indication. Neomycin, metronidazole and vancomycin may be used as alternative treatments for patients intolerant or unresponsive to non-absorbable disaccharides. Antimicrobials reduce bacterial production of ammonia and other bacteria-derived toxins through suppression of intestinal flora. Neomycin has been reported to be as effective as lactulose, and similar efficacy has been reported with vancomycin and metronidazole for the management of HE. However, the adverse effects frequently associated with these antimicrobials limit their use as first-line pharmacological agents. Neomycin is the most commonly used antimicrobial for HE and, although poorly absorbed, systemic exposure to the drug in sufficient amounts causes hearing loss and renal toxicity. Long-term neomycin therapy requires annual auditory testing and continuous monitoring of renal function. Long-term use of metronidazole has been

  20. Contribution of delta bilirubin to the interpretation of hyperbilirubinemia in the horse - a pilot study.

    PubMed

    Lumsden, J H; Jacobs, R M; Physick-Sheard, P

    1991-03-01

    A study was conducted to examine the relationship of delta bilirubin to traditional bilirubin fractions to determine if delta bilirubin might assist in differentiating causes of hyperbilirubinemia in the horse. A recently introduced thin-film method was used for delta bilirubin determination. Thin-film and the traditional diazo methods were used for determining total, unconjugated, and conjugated bilirubin fractions. Sera from 38 healthy and 85 sick horses were examined.Thin-film serum delta bilirubin determination does not appear to assist in differentiating causes of unconjugated hyperbilirubinemia in horses. There was good correlation between thin-film and diazo-determined total bilirubin and bilirubin fractions. Only small changes in reference limits would appear to be necessary for clinical application of the thin-film bilirubin methods used in this study. PMID:17423755

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

  3. Encephalopathy after persistent vomiting: Three cases of non-alcohol-related Wernicke's encephalopathy.

    PubMed

    Antel, K; Singh, N; Chisholm, B; Heckmann, J M

    2015-06-01

    Wernicke's encephalopathy (WE) is a medical emergency. Although WE is commonly viewed in the context of alcoholism, it can be caused by thiamine deficiency secondary to persistent vomiting. Non-alcohol-related WE may be more catastrophic in onset and less likely to present with the classic features than WE with alcoholism as a cause. We describe three cases of WE due to persistent vomiting without alcoholism in patients with hyperemesis gravidarum, drug-induced hyperlactataemia, and an acute gastrointestinal illness in an already malnourished individual. Our cases highlight the importance of recognising WE when undernutrition, which may be caused by gastrointestinal disease or surgery, or malignancy, is compounded by vomiting. Expert guidelines suggest that WE must be considered in the emergency room in any individual with disturbed consciousness of unknown cause. Treatment is with parenteral thiamine before glucose administration. PMID:26716155

  4. FT-IR Study On The Hydration Of Calcium Bilirubinates

    NASA Astrophysics Data System (ADS)

    Guo, Hai; Soloway, Roger D.; Yang, Zhanlan; Ding, Xiao-Chun; Xu, Duan-Fu; Wu, Jin-Guang

    1989-12-01

    Comparison of the dessicated and hydrated forms of the neutral salt of calcium bilirubinate indicated that water alters both the C-E1 skeleton and the polar groups of the molecule, suggesting that water may considerably alters the conformation and, therefore, the properties of calcium bilirubinate. The small degree of swelling indicates that some cross-linking is present in this ionic polymer but that it is much less than in whole pigment gallstones, suggesting that other molecules, possibly glycoproteins, provide much of the cross-linking.

  5. Preterm Hypoxic–Ischemic Encephalopathy

    PubMed Central

    Gopagondanahalli, Krishna Revanna; Li, Jingang; Fahey, Michael C.; Hunt, Rod W.; Jenkin, Graham; Miller, Suzanne L.; Malhotra, Atul

    2016-01-01

    Hypoxic–ischemic encephalopathy (HIE) is a recognizable and defined clinical syndrome in term infants that results from a severe or prolonged hypoxic–ischemic episode before or during birth. However, in the preterm infant, defining hypoxic–ischemic injury (HII), its clinical course, monitoring, and outcomes remains complex. Few studies examine preterm HIE, and these are heterogeneous, with variable inclusion criteria and outcomes reported. We examine the available evidence that implies that the incidence of hypoxic–ischemic insult in preterm infants is probably higher than recognized and follows a more complex clinical course, with higher rates of adverse neurological outcomes, compared to term infants. This review aims to elucidate the causes and consequences of preterm hypoxia–ischemia, the subsequent clinical encephalopathy syndrome, diagnostic tools, and outcomes. Finally, we suggest a uniform definition for preterm HIE that may help in identifying infants most at risk of adverse outcomes and amenable to neuroprotective therapies. PMID:27812521

  6. [Wernicke encephalopathy accompanying linitis plastica].

    PubMed

    Soós, Zsuzsanna; Salamon, Mónika; Oláh, Roland; Czégeni, Anna; Salamon, Ferenc; Folyovich, András; Winkler, Gábor

    2014-01-01

    Wernicke encephalopathy (or Wernicke-Korsakoff encephalopathy) is a rarely diagnosed neurological disorder, which is caused by vitamin B1 deficiency. In the classical form it is characterized by a typical triad (confusion, oculomotor disturbance and ataxia), however, in the majority of the cases only confusion is present. It can be frequently observed in subjects with chronic alcohol consumption, but it may accompany different pathological states of which end stage malignant diseases are the most importants, where confusion may have different backgrounds. The authors present the case of an old male patient with advanced gastric cancer recognised and treated vitamin B1 deficiency, and they draw attention to difficulties of the diagnosis of Wernicke's disease. PMID:24379094

  7. Hepatic encephalopathy: diagnosis and treatment.

    PubMed

    Salgado, Melissa; Cortes, Yonaira

    2013-06-01

    Hepatic encephalopathy (HE) is a neurologic syndrome resulting from the synergistic action of multiple pathologic factors, which are discussed in a companion article. Early recognition of the clinical signs can improve treatment outcome, as well as reduce the incidence of risk factors. Multimodal treatment of HE is usually indicated. Studies on the pathogenesis and treatment of HE in people may shed new light on further treatment modalities in small animal patients. PMID:23677823

  8. Current Concepts in the Pathophysiology and Management of Hepatic Encephalopathy

    PubMed Central

    2011-01-01

    Hepatic encephalopathy (HE) represents a broad continuum of neuropsychological dysfunction in patients with acute or chronic liver disease and/or portosystemic shunting of blood flow. The pathophysiology of this disease is quite complex, as it involves overproduction and reduced metabolism of various neurotoxins, particularly ammonia. Recent hypotheses implicate low-grade cerebral edema as a final common pathway for the pathophysiology of HE. Management of this condition is multifaceted and requires several steps: elimination of precipitating factors; removal of toxins, both by reducing them at their source and by augmenting scavenging pathways; modulation of resident fecal flora; proper nutritional support; and downregulation of systemic and gut-derived inflammation. PMID:21857820

  9. Contemporary Understanding and Management of Overt and Covert Hepatic Encephalopathy.

    PubMed

    NeSmith, Meghan; Ahn, Joseph; Flamm, Steven L

    2016-02-01

    Hepatic encephalopathy (HE) is a major complication of liver disease that leads to significant morbidity and mortality. Caring for hospitalized patients with HE is becoming more complex, and the economic burden of HE continues to rise. Defining and diagnosing HE, particularly covert HE (CHE), remain challenging. In this article, we review new tools and those currently under development for the diagnosis of CHE and the latest advances in the acute and long-term management of overt HE (OHE) and CHE. In particular, we review the latest data on the use of lactulose and rifaximin for treatment of OHE and summarize the data on adjunctive agents such as sodium benzoate and probiotics.

  10. Blood transfusion in sickle cell disease leading to posterior reversible encephalopathy syndrome (PRES).

    PubMed

    Raj, Shashi; Killinger, James; Overby, Philip

    2013-10-01

    Children with sickle cell disease have a very high risk of lifelong neurologic morbidity and mortality. Cerebrovascular accidents are a known complication in children with sickle cell disease. Posterior reversible encephalopathy syndrome is a constellation of acute neurologic findings increasingly recognized in pediatric critical care population with evidence of vasogenic edema on brain imaging possibly due to cerebral vascular endothelial cell dysfunction. This report, for the first time, describes a young adult with sickle cell disease who developed posterior reversible encephalopathy syndrome following blood transfusion. PMID:22899796

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

    PubMed

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

    2016-08-16

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

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

    ERIC Educational Resources Information Center

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

    2006-01-01

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

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

    PubMed

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

    2016-08-16

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

  14. Bilirubin, copper-porphyrins, and the bronze-baby syndrome.

    PubMed

    McDonagh, Antony F

    2011-01-01

    Controlled in vitro spectroscopic measurements reveal that bilirubin does not photosensitize the degradation of copper-porphyrins, as has been proposed for the mechanism of the bronze-baby syndrome, an uncommon side-effect of phototherapy. Calculations also show that copper-porphyrins are unlikely to cause the "bronzing." In conclusion, the copper-porphyrin hypothesis is photochemically implausible.

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

    PubMed Central

    Seshadri, Mandalam Subramanian

    2016-01-01

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

  16. Bilirubin and amyloid-beta peptide induce cytochrome c release through mitochondrial membrane permeabilization.

    PubMed Central

    Rodrigues, C. M.; Solá, S.; Silva, R.; Brites, D.

    2000-01-01

    BACKGROUND: The pathogenesis of bilirubin encephalopathy and Alzheimer's disease appears to result from accumulation of unconjugated bilirubin (UCB) and amyloid-beta (Abeta) peptide, respectively, which may cause apoptosis. Permeabilization of the mitochondrial membrane, with release of intermembrane proteins, has been strongly implicated in cell death. Inhibition of the mitochondrial permeability is one pathway by which ursodeoxycholate (UDC) and tauroursodeoxycholate (TUDC) protect against apoptosis in hepatic and nonhepatic cells. In this study, we further characterize UCB- and Abeta-induced cytotoxicty in isolated neural cells, and investigate membrane perturbation during incubation of isolated mitochondria with both agents. In addition, we evaluate whether the anti-apoptotic drugs UDC and TUDC prevent any changes from occurring. MATERIALS AND METHODS: Primary rat neuron and astrocyte cultures were incubated with UCB or Abeta peptide, either alone or in the presence of UDC. Apoptosis was assessed by DNA fragmentation and nuclear morphological changes. Isolated mitochondria were treated with each toxic, either alone or in combination with UDC, TUDC, or cyclosporine A. Mitochondrial swelling was measured spectrophotometrically and cytochrome c protein levels determined by Western blot. RESULTS: Incubation of neural cells with both UCB and Abeta induced apoptosis (p < 0.01). Coincubation with UDC reduced apoptosis by > 50% (p < 0.05). Both toxins caused membrane permeabilization in isolated mitochondria (p < 0.001); whereas, pretreatment with UDC was protective (p < 0.05). TUDC was even more effective at preventing matrix swelling mediated by Abeta (p < 0.01). UDC and TUDC markedly reduced cytochrome c release associated with mitochondrial permeabilization induced by UCB and Abeta, respectively (p < 0.05). Moreover, cyclosporine A significantly inhibited mitochondrial swelling and cytochrome c efflux mediated by UCB (p < 0.05). CONCLUSION: UCB and Abeta peptide

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

    PubMed

    Mustafa, Mir Faisal; Bano, Bilqees

    2014-05-01

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

  18. FT-IR Spectra And Normal Vibrational Analysis Of Bilirubin IX α

    NASA Astrophysics Data System (ADS)

    Wang, Xiu-Zhen; Soloway, Roger D.; Wu, Jin-Guang; Yu, Bao-Zhu; Xu, Guang-Xian

    1989-12-01

    Bilirubin (C33H36N406) is a water insoluble breakdown product of hemoglobin. It is of biological importance. For example, it can bind with calcium ions to form calcium bilirubinates which are major components in human pigment gallstones. The identification of IR bands of bilirubin are incomplete and the band assignments by different authors have not coincided.

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

    PubMed Central

    Billing, B H

    1978-01-01

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

  20. Susceptibility of European red deer (Cervus elaphus elaphus) to alimentary challenge with bovine spongiform encephalopathy.

    PubMed

    Dagleish, Mark P; Martin, Stuart; Steele, Philip; Finlayson, Jeanie; Eaton, Samantha L; Sisó, Sílvia; Stewart, Paula; Fernández-Borges, Natalia; Hamilton, Scott; Pang, Yvonne; Chianini, Francesca; Reid, Hugh W; Goldmann, Wilfred; González, Lorenzo; Castilla, Joaquín; Jeffrey, Martin

    2015-01-01

    European red deer (Cervus elaphus elaphus) are susceptible to the agent of bovine spongiform encephalopathy, one of the transmissible spongiform encephalopathies, when challenged intracerebrally but their susceptibility to alimentary challenge, the presumed natural route of transmission, is unknown. To determine this, eighteen deer were challenged via stomach tube with a large dose of the bovine spongiform encephalopathy agent and clinical signs, gross and histological lesions, presence and distribution of abnormal prion protein and the attack rate recorded. Only a single animal developed clinical disease, and this was acute with both neurological and respiratory signs, at 1726 days post challenge although there was significant (27.6%) weight loss in the preceding 141 days. The clinically affected animal had histological lesions of vacuolation in the neuronal perikaryon and neuropil, typical of transmissible spongiform encephalopathies. Abnormal prion protein, the diagnostic marker of transmissible encephalopathies, was primarily restricted to the central and peripheral nervous systems although a very small amount was present in tingible body macrophages in the lymphoid patches of the caecum and colon. Serial protein misfolding cyclical amplification, an in vitro ultra-sensitive diagnostic technique, was positive for neurological tissue from the single clinically diseased deer. All other alimentary challenged deer failed to develop clinical disease and were negative for all other investigations. These findings show that transmission of bovine spongiform encephalopathy to European red deer via the alimentary route is possible but the transmission rate is low. Additionally, when deer carcases are subjected to the same regulations that ruminants in Europe with respect to the removal of specified offal from the human food chain, the zoonotic risk of bovine spongiform encephalopathy, the cause of variant Creutzfeldt-Jakob disease, from consumption of venison is probably

  1. Outcome After Therapeutic Hypothermia in Term Neonates With Encephalopathy and a Syndromic Diagnosis.

    PubMed

    Mrelashvili, Anna; Bonifacio, Sonia L; Rogers, Elizabeth E; Shimotake, Thomas K; Glass, Hannah C

    2015-10-01

    The large randomized, controlled trials of therapeutic hypothermia for hypoxic-ischemic encephalopathy excluded neonates with congenital disorders. The objective of this study was to report our experience using hypothermia in neonates with signs of hypoxic-ischemic encephalopathy and a syndromic disorder or brain anomaly. Subjects were identified from a database of neonates admitted to the Neuro-Intensive Care Nursery at University of California, San Francisco. Of 169 patients fulfilling criteria for hypothermia, 8 (5%) had a syndromic disorder and were cooled per guidelines for nonsyndromic neonates. Perinatal characteristics of infants with and without syndromic disorder were not significantly different. Overall outcome was poor: 38% had evidence of acute hypoxic-ischemic injury, 3 subjects died, and 2 survivors had low developmental quotient (ie, 25). The risk versus benefit of therapeutic hypothermia for hypoxic-ischemic encephalopathy among neonates with congenital brain malformations or syndromic diagnoses is uncertain.

  2. Outcome After Therapeutic Hypothermia in Term Neonates With Encephalopathy and a Syndromic Diagnosis.

    PubMed

    Mrelashvili, Anna; Bonifacio, Sonia L; Rogers, Elizabeth E; Shimotake, Thomas K; Glass, Hannah C

    2015-10-01

    The large randomized, controlled trials of therapeutic hypothermia for hypoxic-ischemic encephalopathy excluded neonates with congenital disorders. The objective of this study was to report our experience using hypothermia in neonates with signs of hypoxic-ischemic encephalopathy and a syndromic disorder or brain anomaly. Subjects were identified from a database of neonates admitted to the Neuro-Intensive Care Nursery at University of California, San Francisco. Of 169 patients fulfilling criteria for hypothermia, 8 (5%) had a syndromic disorder and were cooled per guidelines for nonsyndromic neonates. Perinatal characteristics of infants with and without syndromic disorder were not significantly different. Overall outcome was poor: 38% had evidence of acute hypoxic-ischemic injury, 3 subjects died, and 2 survivors had low developmental quotient (ie, 25). The risk versus benefit of therapeutic hypothermia for hypoxic-ischemic encephalopathy among neonates with congenital brain malformations or syndromic diagnoses is uncertain. PMID:25762585

  3. Palatal-Myoclonus as a Presentation of Hashimoto Encephalopathy: an interesting case report

    PubMed Central

    Shahidi, Gholam Ali; Rohani, Mohammad; Nabavi, Mohammad; Aghaei, Mahbubeh; Akhoundi, Fahimeh Haji

    2013-01-01

    Objective Hashimoto encephalopathy (HE) is known as a steroid- responsive encephalopathy associated with autoimmune thyroiditis or nonvascular inflammation-related autoimmune meningoencephalitis. The average age of onset of HE is approximately 50 years; and it is more common in women. The onset of HE may be acute or subacute. The course of most HE cases is relapsing and remitting, which is similar to that of vasculitis and stroke. Methods In this article, we present a previously healthy 32 years old;veterinarian male with palatal myoclonus, as a rare presentation of this disorder, and review the neurologic aspects of hashimoto encephalitis. Results The clinical presentation of HE is characterized by progressive cognitive decline tremor, transient aphasia, seizures, abnormal gait, sleep disorder and stroke-like episodes. Myoclonus, either generalized or multifocal, and tremor, often of the bilateral upper extremities, is the most frequently observed involuntary movements in HE. Conclusion The rapidly progressive cognitive dysfunction and encephalopathies observed. PMID:24454425

  4. The why and wherefore of hepatic encephalopathy

    PubMed Central

    Grover, Vijay PB; Tognarelli, Joshua M; Massie, Nicolas; Crossey, Mary ME; Cook, Nicola A; Taylor-Robinson, Simon D

    2015-01-01

    Hepatic encephalopathy is a common neuropsychiatric abnormality, which complicates the course of patients with liver disease. It was probably first described by Hippocrates over 2000 years ago, who said that “those whose madness arises from phlegm are quiet and neither shout nor make a disturbance, while those whose madness arises from bile shout, play tricks and will not keep still, but are always up to some mischief ”. He was presumably describing the differences between patients with pneumonia and acute liver failure. Despite the fact that the syndrome was probably first recognized thousands of years ago, the exact pathogenesis still remains unclear. Furthermore, a precise definition of the syndrome is lacking, as are definitive methods of diagnosing this condition. It is important as both patients with cirrhosis and the general population with whom they interact may be affected as a consequence. At a minimum, the individual may be affected by impaired quality of life, impaired ability to work, and slowed reaction times, which are relevant to the population at large if affected individuals operate heavy machinery or drive a car. Pathogenic mechanisms, diagnostic tools, and treatment options are discussed. PMID:26719720

  5. The why and wherefore of hepatic encephalopathy.

    PubMed

    Grover, Vijay Pb; Tognarelli, Joshua M; Massie, Nicolas; Crossey, Mary Me; Cook, Nicola A; Taylor-Robinson, Simon D

    2015-01-01

    Hepatic encephalopathy is a common neuropsychiatric abnormality, which complicates the course of patients with liver disease. It was probably first described by Hippocrates over 2000 years ago, who said that "those whose madness arises from phlegm are quiet and neither shout nor make a disturbance, while those whose madness arises from bile shout, play tricks and will not keep still, but are always up to some mischief ". He was presumably describing the differences between patients with pneumonia and acute liver failure. Despite the fact that the syndrome was probably first recognized thousands of years ago, the exact pathogenesis still remains unclear. Furthermore, a precise definition of the syndrome is lacking, as are definitive methods of diagnosing this condition. It is important as both patients with cirrhosis and the general population with whom they interact may be affected as a consequence. At a minimum, the individual may be affected by impaired quality of life, impaired ability to work, and slowed reaction times, which are relevant to the population at large if affected individuals operate heavy machinery or drive a car. Pathogenic mechanisms, diagnostic tools, and treatment options are discussed. PMID:26719720

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

    NASA Astrophysics Data System (ADS)

    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 (< 70 nM at 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. Photodamage of the cells in culture sensitized with bilirubin

    NASA Astrophysics Data System (ADS)

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

    2016-08-01

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

  8. Transcutaneous bilirubin measurement in healthy Saudi term newborns

    PubMed Central

    Alsaedi, Saad A.

    2016-01-01

    Objectives: To evaluate the accuracy of transcutaneous bilirubin (TcB) measurement in healthy, jaundiced Saudi term newborns. Methods: This prospective, cohort study was carried out from January 2009 to December 2012 on jaundiced, term infants admitted at the King Abdulaziz University Hospital, Jeddah, Kingdom of Saudi Arabia. Paired TcB and total serum bilirubin (TSB) from healthy jaundiced term newborns were obtained. The correlation and the mean difference between the 2 methods were calculated, and Bhutani nomogram for prediction of TSB by TcB was used. Any bilirubin level at low and above the intermediate risk zone was considered significant. Results: We obtained 665 paired TcB and TSB measurements from 665 newborns. The mean age at bilirubin measurement was 44.2 ± 21 hour. Mean TSB was 147 ± 45 µmol/L, and TcB was 156 ± 50 µmol/L. Linear regression analysis showed a significant correlation between TcB and TSB (r: 0.84; 95% confidence interval [CI] = 0.82-0.86; p<0.001). The TcB tends to overestimate TSB. The mean difference between paired TcB and TSB was 17 µmol /L with a 95% CI of 40 ± 77 µmol/L. The TcB was sensitive, but less specific. The TcB sensitivity was 83% and specificity was 71% to predict TSB during the first 72 hours of life for the whole study group. The positive predictive value was 63%, and negative predictive value was 87%. Conclusion: As found in this study, among the jaundiced healthy term Saudi newborns, TcB measurement provided accurate estimates of TSB values. The TcB measurements can be used effectively to screen newborns for significant jaundice. PMID:26837395

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

    PubMed

    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.

  10. Multistimuli-Responsive Bilirubin Nanoparticles for Anticancer Therapy.

    PubMed

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

    2016-08-26

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

  11. Encephalopathy

    MedlinePlus

    ... pressure in the skull, prolonged exposure to toxic elements (including solvents, drugs, radiation, paints, industrial chemicals, and certain metals), chronic progressive trauma, poor nutrition, ...

  12. Treatment of Overt Hepatic Encephalopathy.

    PubMed

    Sussman, Norman L

    2015-08-01

    Hepatic encephalopathy (HE) is defined by an altered mental status in the setting of portosystemic shunting, with or without cirrhosis. The basis of HE is probably multi-factorial, but increased ammonia delivery to the brain is thought to play a pivotal role. Medical therapies have typically focused on reducing blood ammonia concentrations. These measures are moderately effective, but further improvements will require identification of new therapeutic targets. Two medications, lactulose and rifaximin, are currently approved for the treatment of HE in the USA - new compounds are available off-label, and are in clinical trials. The presence of HE is associated with a higher risk of death in cirrhotic patients. Liver transplantation typically cures HE, but HE does not increase the MELD score, and therefore does not contribute to the likelihood of liver transplantation. PMID:26195208

  13. Suicide and Chronic Traumatic Encephalopathy.

    PubMed

    Iverson, Grant L

    2016-01-01

    For nearly 80 years, suicidality was not considered to be a core clinical feature of chronic traumatic encephalopathy (CTE). In recent years, suicide has been widely cited as being associated with CTE, and now depression has been proposed to be one of three core diagnostic features alongside cognitive impairment and anger control problems. This evolution of the clinical features has been reinforced by thousands of media stories reporting a connection between mental health problems in former athletes and military veterans, repetitive neurotrauma, and CTE. At present, the science underlying the causal assumption between repetitive neurotrauma, depression, suicide, and the neuropathology believed to be unique to CTE is inconclusive. Epidemiological evidence indicates that former National Football League players, for example, are at lower, not greater, risk for suicide than men in the general population. This article aims to discuss the critical issues and literature relating to these possible relationships. PMID:26449269

  14. Bovine Spongiform Encephalopathy: Atypical Pros and Cons

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Transmissible spongiform encephalopathies (TSEs) are fatal neurologic diseases that affect several mammalian species including human beings. Four animal TSE agents have been reported: scrapie of sheep and goats; chronic wasting disease (CWD) of deer, elk, and moose; transmissible mink encephalopath...

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    1977-01-01

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

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

    PubMed Central

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

    1977-01-01

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

  18. Prospective case-control study of encephalopathy in children with dengue hemorrhagic fever.

    PubMed

    Cam, B V; Fonsmark, L; Hue, N B; Phuong, N T; Poulsen, A; Heegaard, E D

    2001-12-01

    We present a prospective case-control study of 27 serologically confirmed dengue hemorrhagic fever (DHF) patients with severe central nervous system symptoms. Dengue associated encephalopathy accounted for 0.5% of 5,400 patients admitted with DHF. The mortality rate among children with encephalopathy was 22%, with the survivors experiencing a complete recovery. Liver enzymes and bilirubin were significantly elevated in the study group. In analysis of the cerebrospinal fluid (CSF), reverse transcriptase-polymerase chain reaction revealed dengue-3-specific RNA in one evaluated case. Dengue-specific immunoglobulin M was detected in CSF in 14 of 22 assessable patients, indicating a localized infection. Magnetic resonance imaging scans showed cerebral edema in the majority of patients, although encephalitis-like changes were less common. There was an equal distribution of primary and secondary infections. On the basis of previous reports and of the findings of our study, DHF probably encompasses an expanding clinical spectrum that infrequently involves encephalitis due to a direct neurotropic effect of dengue virus.

  19. Bovine spongiform encephalopathy: "mad cow disease".

    PubMed

    1996-07-01

    Bovine spongiform encephalopathy (BSE), also known as "mad cow disease," is a fatal brain disease of cattle first recognized in the United Kingdom. In humans, the most common transmissible spongiform encephalopathy is Creutzfeldt-Jacob Disease (CJD). Although no cases of CJD have been directly linked to beef consumption, an advisory committee has reported that 10 recent cases of a CJD variant may be associated with BSE. This announcement has alarmed consumers well beyond the borders of the United Kingdom.

  20. Hepatic encephalopathy: An approach to its multiple pathophysiological features

    PubMed Central

    Perazzo, Juan Carlos; Tallis, Silvina; Delfante, Amalia; Souto, Pablo Andrés; Lemberg, Abraham; Eizayaga, Francisco Xavier; Romay, Salvador

    2012-01-01

    Hepatic encephalopathy (HE) is a neuropsychiatric complex syndrome, ranging from subtle behavioral abnormalities to deep coma and death. Hepatic encephalopathy emerges as the major complication of acute or chronic liver failure. Multiplicity of factors are involved in its pathophysiology, such as central and neuromuscular neurotransmission disorder, alterations in sleep patterns and cognition, changes in energy metabolism leading to cell injury, an oxidative/nitrosative state and a neuroinflammatory condition. Moreover, in acute HE, a condition of imminent threat of death is present due to a deleterious astrocyte swelling. In chronic HE, changes in calcium signaling, mitochondrial membrane potential and long term potential expression, N-methyl-D-aspartate-cGMP and peripheral benzodiazepine receptors alterations, and changes in the mRNA and protein expression and redistribution in the cerebral blood flow can be observed. The main molecule indicated as responsible for all these changes in HE is ammonia. There is no doubt that ammonia, a neurotoxic molecule, triggers or at least facilitates most of these changes. Ammonia plasma levels are increased two- to three-fold in patients with mild to moderate cirrhotic HE and up to ten-fold in patients with acute liver failure. Hepatic and inter-organ trafficking of ammonia and its metabolite, glutamine (GLN), lead to hyperammonemic conditions. Removal of hepatic ammonia is a differentiated work that includes the hepatocyte, through the urea cycle, converting ammonia into GLN via glutamine synthetase. Under pathological conditions, such as liver damage or liver blood by-pass, the ammonia plasma level starts to rise and the risk of HE developing is high. Knowledge of the pathophysiology of HE is rapidly expanding and identification of focally localized triggers has led the development of new possibilities for HE to be considered. This editorial will focus on issues where, to the best of our knowledge, more research is needed in

  1. Reduction of biliverdin and placental transfer of bilirubin and biliverdin in the pregnant guinea pig.

    PubMed Central

    McDonagh, A F; Palma, L A; Schmid, R

    1981-01-01

    Biliverdin was reduced to bilirubin in pregnant and foetal guinea pigs, and the 100000 g supernatant from homogenates of foetal liver, placenta and maternal liver showed high biliverdin reductase activity. The placental transport of unconjugated bilirubin and biliverdin was compared by injecting unlabelled and radiolabelled pigments into the foetal or maternal circulation and analysing blood collected from the opposite side of the placenta. Injected bilirubin crossed the placenta from foetus to mother and vice versa, but injected biliverdin did not appear to cross without prior reduction to bilirubin. The guinea-pig placenta is apparently more permeable to bilirubin than biliverdin. Reduction of biliverdin to bilirubin in the foetus may, therefore, be essential for efficient elimination of haem catabolites from the foetus in placental mammals. PMID:7305981

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

    PubMed

    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.

  3. Induction of human UGT1A1 by bilirubin through AhR dependent pathway.

    PubMed

    Togawa, Hiroshi; Shinkai, Shigeko; Mizutani, Takaharu

    2008-12-01

    UDP-glucuronosyltransferase1A1 (UGT1A1) plays a key role to conjugate bilirubin and preventing jaundice, but there is no report showing the induction of human UGT1A1 (UGT1A1) by bilirubin. In this report, we show findings of the induction of the reporter gene (-3475/+14) of UGT1A1 in HepG2 cells by bilirubin at 50 microM, 100 microM, with human aryl hydrocarbon receptor (hAhR). We confirmed that induction of the reporter gene by bilirubin is dependent on the position of the xenobiotic responsive element (XRE) (-3328/-3319) of UGT1A1, because the XRE deletion UGT1A1 gene did not respond to stimulation by a complex of bilirubin and hAhR. alpha-Naphthoflavone (alpha-NF) of a typical AhR antagonist at 50 microM inhibited induction by bilirubin, suggesting that bilirubin stimulates through binding with hAhR. Meanwhile, bilirubin itself did not stimulate the induction of AhR, because we detected no-elevation of the mRNA level of AhR by RT-PCR. These results indicate that the induction of UGT1A1 by bilirubin-AhR did not depend on the elevation of AhR but on ligand binding. From this result, we considered that high bilirubin in neonates must induce the elevation of UGT1A1 after birth to prevent jaundice, and bilirubin in adults also regulates the level of UGT1A1. This is the first report showing direct induction of UGT1A1 by a bilirubin through AhR pathway. PMID:19356098

  4. Bilirubin Glucuronidation Revisited: Proper Assay Conditions to Estimate Enzyme Kinetics with Recombinant UGT1A1

    PubMed Central

    Zhou, Jin; Tracy, Timothy S.

    2010-01-01

    Bilirubin, an end product of heme catabolism, is primarily eliminated via glucuronic acid conjugation by UGT1A1. Impaired bilirubin conjugation, caused by inhibition of UGT1A1, can result in clinical consequences, including jaundice and kernicterus. Thus, evaluation of the ability of new drug candidates to inhibit UGT1A1-catalyzed bilirubin glucuronidation in vitro has become common practice. However, the instability of bilirubin and its glucuronides presents substantial technical challenges to conduct in vitro bilirubin glucuronidation assays. Furthermore, because bilirubin can be diglucuronidated through a sequential reaction, establishment of initial rate conditions can be problematic. To address these issues, a robust high-performance liquid chromatography assay to measure both bilirubin mono- and diglucuronide conjugates was developed, and the incubation conditions for bilirubin glucuronidation by human embryonic kidney 293-expressed UGT1A1 were carefully characterized. Our results indicated that bilirubin glucuronidation should be assessed at very low protein concentrations (0.05 mg/ml protein) and over a short incubation time (5 min) to assure initial rate conditions. Under these conditions, bilirubin total glucuronide formation exhibited a hyperbolic (Michaelis-Menten) kinetic profile with a Km of ∼0.2 μM. In addition, under these initial rate conditions, the relative proportions between the total monoglucuronide and the diglucuronide product were constant across the range of bilirubin concentration evaluated (0.05–2 μM), with the monoglucuronide being the predominant species (∼70%). In conclusion, establishment of appropriate incubation conditions (i.e., very low protein concentrations and short incubation times) is necessary to properly characterize the kinetics of bilirubin glucuronidation in a recombinant UGT1A1 system. PMID:20668247

  5. Conjugated bilirubin affects cytokine profiles in hepatitis A virus infection by modulating function of signal transducer and activator of transcription factors.

    PubMed

    Castro-García, Flor P; Corral-Jara, Karla F; Escobedo-Melendez, Griselda; Sandoval-Hernandez, Monserrat A; Rosenstein, Yvonne; Roman, Sonia; Panduro, Arturo; Fierro, Nora A

    2014-12-01

    Hepatitis A virus (HAV) infection is the major cause of acute liver failure in paediatric patients. The clinical spectrum of infection is variable, and liver injury is determined by altered hepatic enzyme function and bilirubin concentration. We recently reported differences in cytokine profiles between distinct HAV-induced clinical courses, and bilirubin has been recognized as a potential immune-modulator. However, how bilirubin may affect cytokine profiles underlying the variability in the course of infection has not been determined. Herein, we used a transcription factor (TF) binding site identification approach to retrospectively analyse cytokine expression in HAV-infected children and to predict the entire set of TFs associated with the expression of specific cytokine profiles. The results suggested that modulation of the activity of signal transducers and activators of transcription proteins (STATs) may play a central role during HAV infection. This led us to compare the degree of STAT phosphorylation in peripheral blood lymphoid cells (PBLCs) from paediatric patients with distinct levels of conjugated bilirubin (CB). Low CB levels in sera were associated with increased STAT-1 and STAT-5 phosphorylation. A positive correlation was observed between the serum interleukin-6 (IL-6) content and CB values, whereas higher levels of CB correlated with reduced serum IL-8 values and with a reduction in the proportion of PBLCs positive for STAT-5 phosphorylation. When CB was used to stimulate patients' PBLCs in vitro, the levels of IL-6 and tumour necrosis factor-α were increased. The data showed that bilirubin plays a role in STAT function and affects cytokine profile expression during HAV infection.

  6. Nicotinic acid test in the diagnosis of Gilbert's syndrome: correlation with bilirubin clearance.

    PubMed Central

    Röllinghoff, W; Paumgartner, G; Preisig, R

    1981-01-01

    A provocation test with nicotinic acid (50 mg intravenously) was performed in 13 patients with Gilbert's syndrome and seven healthy volunteers to investigate the diagnostic value of several test parameters and to correlate them with the bilirubin clearance. The maximal increment of unconjugated serum bilirubin, the retention at four hours, and the area under the bilirubin concentration time curve. (AUC) were measured. Significant differences between patients and controls were found with regard to the AUC (7.95 +/- SD, 3.29 mmol/min/l vs. 3.08 +/- 0.57; P less than 0.001), the increment of unconjugated bilirubin (24.1 +/- 7.1 mumol/l vs. 10.2 +/- 3.2; P less than 0.001) and the retention (77.7 +/- 8.9% vs. 45.8 +/- 27.4%; P less than 0.02). Of those, the AUC discriminated best between patients and controls. Five patients with Gilbert's syndrome had normal serum bilirubin concentrations (less than 17.1 mumol/l = 1 mg%) at the time of the study, but abnormal AUC and bilirubin increment. A significant correlation was found between the bilirubin clearance and the retention (r = -0.96; P less than 0.001) as well as the AUC (r = -0.82; P less than 0.05) but not with the bilirubin increment. This simple test may be used to assess the disturbance of bilirubin clearance in Gilbert's syndrome. PMID:7286783

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

    PubMed

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

    2015-01-01

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

  8. The mechanism of haem catabolism. Bilirubin formation in living rats by [18O]oxygen labelling.

    PubMed Central

    Brown, S B; King, R F

    1978-01-01

    1. The pathway of haem breakdown in living rats was studied by using 18O in the oxygen that the animals consumed. By cannulation of the common bile duct and collection of bile, labelled bilirubin was isolated and its mass spectrum determined. One set of results was obtained for a rat to which haemoglobin had been intravenously administered and another set obtained for a rat that was not given exogenous haem. Isomerization of bilirubin IXalpha to the XIIIalpha and IIIalpha isomers did not occur to any significant extent. The 18O-labelling pattern obtained in the bilirubin was consistent with a Two-Molecule Mechanism, whereby the terminal lactam oxygen atoms of bilirubin are derived from different oxygen molecules. The consequences of this mechanism are discussed in terms of the possible intermediates of the catabolic pathway. 2. 18O-labelled bilirubin appeared in the bile in less than 10 min after exposure of the animals to labelled oxygen. This result suggests that all of the chemical transformations involving production of biliverdin, reduction to bilirubin and conjugation of the bilirubin are fast processes. 3. The quantitative recovery of label obtained in the experiments suggests that there is little or no exchange of newly synthesized bilirubin with existing bilirubin pools in the animal. PMID:637844

  9. 21 CFR 862.1110 - Bilirubin (total or direct) test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test... or serum. Measurements of the levels of bilirubin, an organic compound formed during the normal...

  10. 21 CFR 862.1110 - Bilirubin (total or direct) test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test... or serum. Measurements of the levels of bilirubin, an organic compound formed during the normal...

  11. 21 CFR 862.1110 - Bilirubin (total or direct) test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test... or serum. Measurements of the levels of bilirubin, an organic compound formed during the normal...

  12. 21 CFR 862.1110 - Bilirubin (total or direct) test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test... or serum. Measurements of the levels of bilirubin, an organic compound formed during the normal...

  13. 21 CFR 862.1110 - Bilirubin (total or direct) test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test... or serum. Measurements of the levels of bilirubin, an organic compound formed during the normal...

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

    PubMed Central

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

    2015-01-01

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

  15. Bilirubin acts as an endogenous regulator of inflammation by disrupting adhesion molecule-mediated leukocyte migration

    PubMed Central

    Vogel, Megan E.; Zucker, Stephen D.

    2016-01-01

    There is a growing body of evidence that bilirubin, which is generated during the physiological breakdown of heme, exerts potent anti-inflammatory effects. Previous work by our group suggests that bilirubin is able to suppress inflammatory responses by preventing the migration of leukocytes into target tissues through disruption of vascular cell adhesion molecule-1 (VCAM-1)-dependent cell signaling. As VCAM-1 is an important mediator 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. As anticipated, bilirubin-treated animals manifested significantly less colonic injury and reduced infiltration of inflammatory cells into colon tissues. We further observed that bilirubin administration was associated with a reduced number of eosinophils and monocytes in the small intestine, with a corresponding increase in peripheral blood eosinophilia, regardless of whether mice received DSS. These findings suggest that bilirubin impairs the normal migration of eosinophils into intestinal tissues, as supported by in vitro experiments showing that bilirubin blocks the VCAM-1-dependent movement of Jurkat cells across human endothelial cell monolayers. Taken together, our findings support that bilirubin ameliorates DSS-induced colitis and disrupts the physiological trafficking of leukocytes to the intestine by preventing transmigration across the vascular endothelium, potentially through the inhibition VCAM-1-mediated signaling. Our findings raise the possibility that bilirubin functions as an endogenous regulator of inflammatory responses. PMID:26925435

  16. Unusual presentation of Gilbert disease with high levels of unconjugated bilirubin. Report of two cases.

    PubMed

    Flores-Villalba, Eduardo; Rodriguez-Montalvo, Carlos; Bosques-Padilla, Francisco; Arredondo-Saldaña, Gabriela; Zertuche-Maldonado, Tania; Torre-Flores, Landy

    2016-04-01

    Gilbert's syndrome is a benign condition characterized by asymptomatic sporadic episodes of jaundice, due to a mild unconjugated hyperbilirubinemia caused by a deficiency in bilirubin glucoronidation. Under certain physiologic or pathologic events bilirubin level rises but according to literature it does not reach out more than 3 mg/dl. We report 2 cases of Gilbert's syndrome, genetically tested, which presented with bilirubin levels above 6 mg/dl without any trigger or coexisting condition. In conclusion, bilirubin levels higher than 6 mg/dL in Gilbert syndrome are rare, hemolytic and other metabolism diseases must be ruled out, and genetic testing may be necessary in some cases. PMID:26181050

  17. 21 CFR 862.1113 - Bilirubin (total and unbound) in the neonate test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

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

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

    Code of Federal Regulations, 2010 CFR

    2010-04-01

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

  19. 21 CFR 862.1113 - Bilirubin (total and unbound) in the neonate test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

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

  20. 21 CFR 862.1115 - Urinary bilirubin and its conjugates (nonquantitative) test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

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

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

    Code of Federal Regulations, 2013 CFR

    2013-04-01

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

  2. 21 CFR 862.1115 - Urinary bilirubin and its conjugates (nonquantitative) test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

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

  3. 21 CFR 862.1113 - Bilirubin (total and unbound) in the neonate test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

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

  4. 21 CFR 862.1113 - Bilirubin (total and unbound) in the neonate test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

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

  5. 21 CFR 862.1115 - Urinary bilirubin and its conjugates (nonquantitative) test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

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

  6. 21 CFR 862.1115 - Urinary bilirubin and its conjugates (nonquantitative) test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

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

  7. Chronic traumatic encephalopathy and athletes.

    PubMed

    Meehan, William; Mannix, Rebekah; Zafonte, Ross; Pascual-Leone, Alvaro

    2015-10-27

    Recent case reports have described athletes previously exposed to repetitive head trauma while participating in contact sports who later in life developed mood disorders, headaches, cognitive difficulties, suicidal ideation, difficulties with speech, and aggressive behavior. Postmortem discoveries show that some of these athletes have pathologic findings that are collectively termed chronic traumatic encephalopathy (CTE). Current hypotheses suggest that concussions or perhaps blows to the head that do not cause the signs and symptoms necessary for making the diagnosis of concussion, so-called subconcussive blows, cause both the clinical and pathologic findings. There are, however, some athletes who participate in contact sports who do not develop the findings ascribed to CTE. Furthermore, there are people who have headaches, mood disorders, cognitive difficulties, suicidal ideation, and other clinical problems who have neither been exposed to repeated head trauma nor possessed the pathologic postmortem findings of those currently diagnosed with CTE. The current lack of prospective data and properly designed case-control studies limits the current understanding of CTE, leading to debate about the causes of the neuropathologic findings and the clinical observations. Given the potential for referral and recall bias in available studies, it remains unclear whether or not the pathologic findings made postmortem cause the presumed neurobehavioral sequela and whether the presumed risk factors, such as sports activity, cerebral concussions, and subconcussive blows, are solely causative of the clinical signs and symptoms. This article discusses the current evidence and the associated limitations. PMID:26253448

  8. Encephalopathy caused by lanthanum carbonate

    PubMed Central

    Cacharro, Luis Maria; Garcia-Cosmes, Pedro; Rosado, Consolacion; Tabernero, Jose Matias

    2011-01-01

    Lanthanum carbonate is a nonaluminum, noncalcium phosphate-binding agent, which is widely used in patients with end-stage chronic kidney disease. Until now, no significant side-effects have been described for the clinical use of lanthanum carbonate, and there are no available clinical data regarding its tissue stores. Here we report the case of a 59-year-old patient who was admitted with confusional syndrome. The patient received 3750 mg of lanthanum carbonate daily. Examinations were carried out, and the etiology of the encephalopathy of the patient could not be singled out. The lanthanum carbonate levels in serum and cerebrospinal fluid were high, and the syndrome eased after the drug was removed. The results of our study confirm that, in our case, the lanthanum carbonate did cross the blood-brain barrier (BBB). Although lanthanum carbonate seems a safe drug with minimal absorption, this work reveals the problem derived from the increase of serum levels of lanthanum carbonate, and the possibility that it may cross the BBB. Further research is required on the possible pathologies that increase serum levels of lanthanum carbonate, as well as the risks and side-effects derived from its absorption. PMID:25984155

  9. Joseph Haydn's encephalopathy: new aspects.

    PubMed

    Blahak, Christian; Bäzner, Hansjörg; Hennerici, Michael G

    2015-01-01

    With increasing age, Joseph Haydn complained of progressive forgetfulness preventing him from composing for about the last 8 years of his life. He spent his days more and more inactive and immobilized, suffering from a disabling gait disturbance. Still, most biographers consider diffuse atherosclerosis and congestive heart failure to be reasons for Haydn's medical condition and physical decline during the last years of his life. A more sophisticated and detailed inspection of documents and sources, however, leads to the diagnosis of subcortical vascular encephalopathy (SVE), caused by progressive cerebral small vessel disease. Important features of the disease are mood changes, urinary symptoms, and in particular a characteristic gait disturbance, while dementia is only mild and occurs later in the course. Haydn was severely disabled by the symptoms of SVE for several years and often reported difficulties in the completion of his last oratorio "Die Jahreszeiten" (The Seasons). Subsequently, the disease prevented him from composing another large oratorio, "Das jüngste Gericht" (The last judgement), which had been already drafted. Finally, the progress of SVE stopped his long career as a composer and conductor at the age of 73 years. PMID:25684297

  10. Clinical Neurophysiology of Hepatic Encephalopathy

    PubMed Central

    Amodio, Piero; Montagnese, Sara

    2015-01-01

    Background/Objectives Hepatic encephalopathy (HE) has relevant impact on the quality of life of patients and their caregivers and causes relevant costs because of hospitalizations and work days lost. Its quantification is important to perform adequate clinical trials on this relevant complication of cirrhosis and portal-systemic shunting. Clinical neurophysiology, which detects functional alterations of the nervous system, has been applied to the study of HE for over 60 years. This review aims at summarizing and clarifying the role of neurophysiologic techniques in the study of HE. Methods A narrative review was performed aiming at interpreting the cited papers and the techniques on the basis of their physiological and pathophysiological meaning. Results The potential role of EEG, quantified EEG, evoked potentials—both exogenous, endogenous and motor—have been clarified to the reader that may be unfamiliar with neurophysiology. Conclusions The EEG, reflecting the oscillatory changes of neural network is the preferable tool to detect and monitor HE, with the exception of its most severe stage, when EEG flattens. SSEP and MEP have indication to detect and monitor transmission alterations that are likely related to myelin changes and microedema. PMID:26041960

  11. Gut microbiota and hepatic encephalopathy.

    PubMed

    Dhiman, Radha K

    2013-06-01

    There is a strong relationship between liver and gut; while the portal venous system receives blood from the gut, and its contents may affect liver functions, liver in turn, affects intestinal functions through bile secretion. There is robust evidence that the pathogenesis of hepatic encephalopathy (HE) is linked to alterations in gut microbiota and their by-products such as ammonia, indoles, oxindoles, endotoxins, etc. In the setting of intestinal barrier and immune dysfunction, these by-products are involved in the pathogenesis of complications of liver cirrhosis including HE and systemic inflammation plays an important role. Prebiotics, probiotics and synbiotics may exhibit efficacy in the treatment of HE by modulating the gut flora. They improve derangement in flora by decreasing the counts of pathogenic bacteria and thus improving the endotoxemia, HE and the liver disease. Current evidence suggest that the trials evaluating the role of probiotics in the treatment of HE are of not high quality and all trials had high risk of bias and high risk of random errors. Therefore, the use of probiotics for patients with HE cannot be currently recommended. Further RCTs are required. This review summarizes the main literature findings about the relationships between gut flora and HE, both in terms of the pathogenesis and the treatment of HE.

  12. Joseph Haydn's encephalopathy: new aspects.

    PubMed

    Blahak, Christian; Bäzner, Hansjörg; Hennerici, Michael G

    2015-01-01

    With increasing age, Joseph Haydn complained of progressive forgetfulness preventing him from composing for about the last 8 years of his life. He spent his days more and more inactive and immobilized, suffering from a disabling gait disturbance. Still, most biographers consider diffuse atherosclerosis and congestive heart failure to be reasons for Haydn's medical condition and physical decline during the last years of his life. A more sophisticated and detailed inspection of documents and sources, however, leads to the diagnosis of subcortical vascular encephalopathy (SVE), caused by progressive cerebral small vessel disease. Important features of the disease are mood changes, urinary symptoms, and in particular a characteristic gait disturbance, while dementia is only mild and occurs later in the course. Haydn was severely disabled by the symptoms of SVE for several years and often reported difficulties in the completion of his last oratorio "Die Jahreszeiten" (The Seasons). Subsequently, the disease prevented him from composing another large oratorio, "Das jüngste Gericht" (The last judgement), which had been already drafted. Finally, the progress of SVE stopped his long career as a composer and conductor at the age of 73 years.

  13. Chronic Traumatic Encephalopathy: A Review

    PubMed Central

    Saulle, Michael; Greenwald, Brian D.

    2012-01-01

    Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disease that is a long-term consequence of single or repetitive closed head injuries for which there is no treatment and no definitive pre-mortem diagnosis. It has been closely tied to athletes who participate in contact sports like boxing, American football, soccer, professional wrestling and hockey. Risk factors include head trauma, presence of ApoE3 or ApoE4 allele, military service, and old age. It is histologically identified by the presence of tau-immunoreactive NFTs and NTs with some cases having a TDP-43 proteinopathy or beta-amyloid plaques. It has an insidious clinical presentation that begins with cognitive and emotional disturbances and can progress to Parkinsonian symptoms. The exact mechanism for CTE has not been precisely defined however, research suggest it is due to an ongoing metabolic and immunologic cascade called immunoexcitiotoxicity. Prevention and education are currently the most compelling way to combat CTE and will be an emphasis of both physicians and athletes. Further research is needed to aid in pre-mortem diagnosis, therapies, and support for individuals and their families living with CTE. PMID:22567320

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

    NASA Astrophysics Data System (ADS)

    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.

  15. SPTAN1 encephalopathy: distinct phenotypes and genotypes.

    PubMed

    Tohyama, Jun; Nakashima, Mitsuko; Nabatame, Shin; Gaik-Siew, Ch'ng; Miyata, Rie; Rener-Primec, Zvonka; Kato, Mitsuhiro; Matsumoto, Naomichi; Saitsu, Hirotomo

    2015-04-01

    Recent progress in genetic analysis reveals that a significant proportion of cryptogenic epileptic encephalopathies are single-gene disorders. Mutations in numerous genes for early-onset epileptic encephalopathies have been rapidly identified, including in SPTAN1, which encodes α-II spectrin. The aim of this review is to delineate SPTAN1 encephalopathy as a distinct clinical syndrome. To date, a total of seven epileptic patients with four different in-frame SPTAN1 mutations have been identified. The major clinical features of SPTAN1 mutations include epileptic encephalopathy with hypsarrhythmia, no visual attention, acquired microcephaly, spastic quadriplegia and severe intellectual disability. Brainstem and cerebellar atrophy and cerebral hypomyelination, as observed by magnetic resonance imaging, are specific hallmarks of this condition. A milder variant is characterized by generalized epilepsy with pontocerebellar atrophy. Only in-frame SPTAN1 mutations in the last two spectrin repeats in the C-terminal region lead to dominant negative effects and these specific phenotypes. The last two spectrin repeats are required for α/β spectrin heterodimer associations and the mutations can alter heterodimer formation between the two spectrins. From these data we suggest that SPTAN1 encephalopathy is a distinct clinical syndrome owing to specific SPTAN1 mutations. It is important that this syndrome is recognized by pediatric neurologists to enable proper diagnostic work-up for patients. PMID:25631096

  16. Hypothermia for hypoxic–ischemic encephalopathy

    PubMed Central

    Cotten, C Michael; Shankaran, Seetha

    2010-01-01

    Moderate to severe hypoxic–ischemic injury in newborn infants, manifested as encephalopathy immediately or within hours after birth, is associated with a high risk of either death or a lifetime with disability. In recent multicenter clinical trials, hypothermia initiated within the first 6 postnatal hours has emerged as a therapy that reduces the risk of death or impairment among infants with hypoxic–ischemic encephalopathy. Prior to hypothermia, no therapies directly targeting neonatal encephalopathy secondary to hypoxic–ischemic injury had convincing evidence of efficacy. Hypothermia therapy is now becoming increasingly available at tertiary centers. Despite the deserved enthusiasm for hypothermia, obstetric and neonatology caregivers, as well as society at large, must be reminded that in the clinical trials more than 40% of cooled infants died or survived with impairment. Although hypothermia is an evidence-based therapy, additional discoveries are needed to further improve outcome after HIE. In this article, we briefly present the epidemiology of neonatal encephalopathy due to hypoxic–ischemic injury, describe the rationale for the use of hypothermia therapy for hypoxic–ischemic encephalopathy, and present results of the clinical trials that have demonstrated the efficacy of hypothermia. We also present findings noted during and after these trials that will guide care and direct research for this devastating problem. PMID:20625441

  17. Severe hypoglycemic encephalopathy due to hypoallergenic formula in an infant.

    PubMed

    Ogawa, Erika; Ishige, Mika; Takahashi, Yuno; Kodama, Hiroko; Fuchigami, Tatsuo; Takahashi, Shori

    2016-08-01

    A 7-month-old girl was brought to hospital due to vomiting. Upon admission, she was in a convulsive state and stupor with extremely low blood glucose. Head computed tomography showed brain edema, and comprehensive treatment for acute encephalopathy was initiated immediately. Severe hypoglycemia, metabolic acidosis, elevation of ammonia and serum transaminases and creatine kinase suggested metabolic decompensation. Infusion of a high-glucose solution containing vitamins, biotin, and l-carnitine resolved the metabolic crisis quickly, but brain damage was irreversible. She was found to have been fed exclusively on a hypoallergenic formula (HF) for 7 months, although she was found later to be non-allergic. Evidence of inborn metabolic diseases was absent, therefore biotin deficiency and carnitine deficiency were concluded to be a consequence of reliance on a HF for a prolonged period. Health-care professionals should warn parents of the consequences of using HF. PMID:27324861

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

    PubMed

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

    2004-08-01

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

  19. Clinical review of genetic epileptic encephalopathies

    PubMed Central

    Noh, Grace J.; Asher, Y. Jane Tavyev; Graham, John M.

    2012-01-01

    Seizures are a frequently encountered finding in patients seen for clinical genetics evaluations. The differential diagnosis for the cause of seizures is quite diverse and complex, and more than half of all epilepsies have been attributed to a genetic cause. Given the complexity of such evaluations, we highlight the more common causes of genetic epileptic encephalopathies and emphasize the usefulness of recent technological advances. The purpose of this review is to serve as a practical guide for clinical geneticists in the evaluation and counseling of patients with genetic epileptic encephalopathies. Common syndromes will be discussed, in addition to specific seizure phenotypes, many of which are refractory to anti-epileptic agents. Divided by etiology, we overview the more common causes of infantile epileptic encephalopathies, channelopathies, syndromic, metabolic, and chromosomal entities. For each condition, we will outline the diagnostic evaluation and discuss effective treatment strategies that should be considered. PMID:22342633

  20. Why the confusion in Hashimoto's encephalopathy?

    PubMed

    Jayasekera, Bodiabaduge A P; McShane, Michael Anthony; Roy, Prem; Anand, Geetha

    2011-01-01

    A 13-year-old girl presented with an afebrile seizure followed by prolonged confusion and visual hallucinations. Initial investigations in the form of blood tests, cerebrospinal fluid analysis and head imaging by CT, were normal. She represented with two further episodes within a period of 3 weeks. Further investigations considering infective, metabolic and some autoimmune causes of encephalopathy were negative. An MRI head scan was normal. Thyroid function testing disclosed primary hypothyroidism and elevated antithyroid antibodies. She responded well to glucocorticoid therapy for presumed Hashimoto's encephalopathy (HE). HE describes patients with various neurological manifestations with elevated titres of antithyroid antibodies. There are no clear criteria for diagnosis, with many cases labelled as HE. Responses to corticosteroid therapy are favourable. In patients with unexplained encephalopathy, HE should be considered given the favourable response to glucocorticoid therapy. PMID:22691944

  1. Wernicke's Encephalopathy Complicating Hyperemesis during Pregnancy.

    PubMed

    Berdai, Mohamed Adnane; Labib, Smael; Harandou, Mustapha

    2016-01-01

    Wernicke's encephalopathy is caused by severe thiamine deficiency; it is mostly observed in alcoholic patients. We report the case of a 28-year-old woman, at 17 weeks of gestational age, with severe hyperemesis gravidarum. She presented with disturbance of consciousness, nystagmus, ophthalmoplegia, and ataxia. The resonance magnetic imagery showed bilaterally symmetrical hyperintensities of thalamus and periaqueductal area. The case was managed with very large doses of thiamine. The diagnosis of Wernicke's encephalopathy was confirmed later by a low thiamine serum level. The patient was discharged home on day 46 with mild ataxia and persistent nystagmus. Wernicke's encephalopathy is a rare complication of hyperemesis gravidarum. It should be diagnosed as early as possible to prevent long-term neurological sequela or death. Thiamine supplementation in pregnant women with prolonged vomiting should be initiated, especially before parenteral dextrose infusion. Early thiamine replacement will reduce maternal morbidity and fetal loss rate. PMID:26989522

  2. Sepsis-associated encephalopathy: not just delirium

    PubMed Central

    Zampieri, Fernando Godinho; Park, Marcelo; Machado, Fabio Santana; Azevedo, Luciano Cesar Pontes

    2011-01-01

    Sepsis is a major cause of mortality and morbidity in intensive care units. Organ dysfunction is triggered by inflammatory insults and tissue hypoperfusion. The brain plays a pivotal role in sepsis, acting as both a mediator of the immune response and a target for the pathologic process. The measurement of brain dysfunction is difficult because there are no specific biomarkers of neuronal injury, and bedside evaluation of cognitive performance is difficult in an intensive care unit. Although sepsis-associated encephalopathy was described decades ago, it has only recently been subjected to scientific scrutiny and is not yet completely understood. The pathophysiology of sepsis-associated encephalopathy involves direct cellular damage to the brain, mitochondrial and endothelial dysfunction and disturbances in neurotransmission. This review describes the most recent findings in the pathophysiology, diagnosis, and management of sepsis-associated encephalopathy and focuses on its many presentations. PMID:22012058

  3. Pediatric Epileptic Encephalopathies: Pathophysiology and Animal Models.

    PubMed

    Shao, Li-Rong; Stafstrom, Carl E

    2016-05-01

    Epileptic encephalopathies are syndromes in which seizures or interictal epileptiform activity contribute to or exacerbate brain function, beyond that caused by the underlying pathology. These severe epilepsies begin early in life, are associated with poor lifelong outcome, and are resistant to most treatments. Therefore, they represent an immense challenge for families and the medical care system. Furthermore, the pathogenic mechanisms underlying the epileptic encephalopathies are poorly understood, hampering attempts to devise novel treatments. This article reviews animal models of the three classic epileptic encephalopathies-West syndrome (infantile spasms), Lennox-Gastaut syndrome, and continuous spike waves during sleep or Landau-Kleffner syndrome-with discussion of how animal models are revealing underlying pathophysiological mechanisms that might be amenable to targeted therapy. PMID:27544466

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

    NASA Astrophysics Data System (ADS)

    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%.

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

    PubMed

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

    2016-04-21

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

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

    ERIC Educational Resources Information Center

    Rubin, Rosalyn A.; And Others

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

  7. Concussion in Chronic Traumatic Encephalopathy

    PubMed Central

    Stein, Thor D.; Alvarez, Victor E.; McKee, Ann C.

    2015-01-01

    Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disease that occurs in association with repetitive mild traumatic brain injury. It is associated with a variety of clinical symptoms in multiple domains, and there is a distinct pattern of pathological changes. The abnormal tau pathology in CTE occurs uniquely in those regions of the brain that are likely most susceptible to stress concentration during trauma. CTE has been associated with a variety of types of repetitive head trauma, most frequently contact sports. In cases published to date, the mean length of exposure to repetitive head trauma was 15.4 years. The clinical symptoms of the disease began after a mean latency of 14.5 years with a mean age of death of 59.3 years. Most subjects had a reported history of concussions with a mean of 20.3. However, 16 % of published CTE subjects did not have a history of concussion suggesting that subconcussive hits are sufficient to lead to the development of CTE. Overall, the number of years of exposure, not the number of concussions, was significantly associated with worse tau pathology in CTE. This suggests that it is the chronic and repetitive nature of head trauma, irrespective of concussive symptoms, that is the most important driver of disease. CTE and exposure to repetitive head trauma is also associated with a variety of other neurodegenerations, including Alzheimer disease. In fact, amyloid β peptide deposition is altered and accelerated in CTE and is associated with worse disease. Here, we review the current exposure, clinical, and pathological associations of CTE. PMID:26260277

  8. Concussion in Chronic Traumatic Encephalopathy.

    PubMed

    Stein, Thor D; Alvarez, Victor E; McKee, Ann C

    2015-10-01

    Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disease that occurs in association with repetitive mild traumatic brain injury. It is associated with a variety of clinical symptoms in multiple domains, and there is a distinct pattern of pathological changes. The abnormal tau pathology in CTE occurs uniquely in those regions of the brain that are likely most susceptible to stress concentration during trauma. CTE has been associated with a variety of types of repetitive head trauma, most frequently contact sports. In cases published to date, the mean length of exposure to repetitive head trauma was 15.4 years. The clinical symptoms of the disease began after a mean latency of 14.5 years with a mean age of death of 59.3 years. Most subjects had a reported history of concussions with a mean of 20.3. However, 16 % of published CTE subjects did not have a history of concussion suggesting that subconcussive hits are sufficient to lead to the development of CTE. Overall, the number of years of exposure, not the number of concussions, was significantly associated with worse tau pathology in CTE. This suggests that it is the chronic and repetitive nature of head trauma, irrespective of concussive symptoms, that is the most important driver of disease. CTE and exposure to repetitive head trauma is also associated with a variety of other neurodegenerations, including Alzheimer disease. In fact, amyloid β peptide deposition is altered and accelerated in CTE and is associated with worse disease. Here, we review the current exposure, clinical, and pathological associations of CTE. PMID:26260277

  9. Transmissible encephalopathies: speculations and realities.

    PubMed

    Manuelidis, Laura

    2003-01-01

    Virtually all transmissible encephalopathies (TSEs), such as scrapie, CJD, and BSE, are caused by a type of infectious particle that remains enigmatic. The language of prion theory supersedes the reality of what is, and what is not known. This review questions the predictive value, consistency and accuracy of this now dominant assumption. Many people believe the normal cellular prion protein (PrP) self-converts into an infectious amyloid protein or prion. Although the amyloidogenic capacity of proteins is well established, the concept of an infectious protein without nucleic acid was "revolutionary." Diverse experiments have repeatedly shown, however, that this protein alone, in any form, is incapable of reproducing transmissible infection. In contrast, the infectious agent copurifies with many other molecules, including nucleic acids, while it separates from the majority of PrP. The infectious particle has a homogeneous viral size of ~25 nm, and infectivity is markedly reduced by conditions that disrupt viral core components but do not disrupt multimers of PrP amyloid. Additionally, the infectious agent replicates to high levels before any PrP abnormalities can be detected. Hence, we initially proposed that PrP changes are part of the host's pathologic response to high levels of infectious agent, but not the agent itself. Newer data clarifying a role for myeloid cells in the spread of infection, the unique character of two different agent strains propagated in a single animal, and the demonstration of long nucleic acids in a variety of simplified high titer preparations continue to raise serious questions for the prion hypothesis. Moreover, the epidemic spread of TSEs, and the activation of host innate immune mechanisms by infection, further indicate these agents are recognizably foreign, and probably viral.

  10. Experimental Interspecies Transmission Studies of the Transmissible Spongiform Encephalopathies to Cattle: Comparison to Bovine Spongiform Encephalopathy in Cattle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Prion diseases or transmissible spongiform encephalopathies (TSEs) of animals include scrapie of sheep and goats; transmissible mink encephalopathy (TME); chronic wasting disease (CWD) of deer, elk and moose; and bovine spongiform encephalopathy (BSE) of cattle. Since the emergence of BSE and its pr...

  11. Dengue fever with encephalopathy in Australia.

    PubMed

    Row, D; Weinstein, P; Murray-Smith, S

    1996-03-01

    During an epidemic of dengue type 2 virus in the rural community of Charters Towers, North Queensland, Australia, in 1993, 210 cases presented to the local hospital with signs and symptoms of classic dengue fever. Two cases were noteworthy because of neurologic complications, which included drowsiness, short term memory loss, agitation, and seizure. The cases are presented in detail because they are the first cases of dengue-associated encephalopathy to be documented in Australia. An increasing number of cases of encephalopathy associated with classic dengue fever is being reported world wide, but the etiology of this clinical syndrome remains unknown.

  12. Metabolism of bilirubin by human cytochrome P450 2A6

    SciTech Connect

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

    2012-05-15

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

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

    PubMed Central

    Ostrow, J Donald; Mukerjee, Pasupati

    2007-01-01

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

  14. Living donor liver transplantation for acute liver failure in pediatric patients caused by the ingestion of fireworks containing yellow phosphorus.

    PubMed

    Ates, Mustafa; Dirican, Abuzer; Ozgor, Dincer; Aydin, Cemalettin; Isik, Burak; Ara, Cengiz; Yilmaz, Mehmet; Ayse Selimoglu, M; Kayaalp, Cuneyt; Yilmaz, Sezai

    2011-11-01

    Yellow phosphorus is a protoplasmic toxicant that targets the liver. The ingestion of fireworks containing yellow phosphorus, either by children who accidentally consume them or by adults who are attempting suicide, often results in death due to acute liver failure (ALF). We present the outcomes of 10 children who ingested fireworks containing yellow phosphorus. There were 6 boys and 4 girls, and their ages ranged from 21 to 60 months. One patient remained stable without liver complications and was discharged. Three patients died of hepatorenal failure and cardiovascular collapse, and living donor liver transplantation (LDLT) was performed for 6 patients. The patients had grade II or III encephalopathy, a mean alanine aminotransferase level of 1148.2 IU/L, a mean aspartate aminotransferase level of 1437.5 IU/L, a mean total bilirubin level of 6.9 mg/dL, a mean international normalized ratio of 6.6, a mean Pediatric End-Stage Liver Disease score of 33.7, and a mean Child-Pugh score of 11.3. Postoperatively, 2 patients had persistent encephalopathy and died on the second or third postoperative day, and 1 patient died of cardiac arrest on the first postoperative day despite a well-functioning graft. The other 3 patients were still alive at a mean of 204 days. In conclusion, the ingestion of fireworks containing yellow phosphorus causes ALF with a high mortality rate. When signs of irreversible ALF are detected, emergency LDLT should be considered as a lifesaving procedure; however, if yellow phosphorus toxicity affects both the brain and the heart in addition to the liver, the mortality rate remains very high despite liver transplantation.

  15. Impact of bilirubin-induced neurologic dysfunction on neurodevelopmental outcomes

    PubMed Central

    Loe, Irene M.

    2015-01-01

    Bilirubin-induced neurologic dysfunction (BIND) is the constellation of neurologic sequelae following milder degrees of neonatal hyperbilirubinemia than are associated with kernicterus. Clinically, BIND may manifest after the neonatal period as developmental delay, cognitive impairment, disordered executive function, and behavioral and psychiatric disorders. However, there is controversy regarding the relative contribution of neonatal hyperbilirubinemia versus other risk factors to the development of later neurodevelopmental disorders in children with BIND. In this review, we focus on the empiric data from the past 25 years regarding neurodevelopmental outcomes and BIND, including specific effects on developmental delay, cognition, speech and language development, executive function, and th neurobehavioral disorders, such as attention deficit/hyperactivity disorder and autism. PMID:25585889

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

    PubMed Central

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

    2015-01-01

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

  17. Posterior reversible encephalopathy syndrome in a child with Henoch-Schönlein purpura

    PubMed Central

    Sivrioglu, Ali Kemal; Incedayi, Mehmet; Mutlu, Hakan; Meral, Cihan

    2013-01-01

    Henoch-Schönlein purpura (HSP) is a small vessel vasculitis that affects the gastrointestinal and central nervous systems and the kidneys. The disease primarily affects children, but may occur in elderly children with allergic purpura and also in adults. Central nervous system involvement may be the first sign; however, it is rarely encountered. Posterior reversible encephalopathy syndrome (PRES) is a clinical syndrome of encephalopathy, headache, visual disturbance and seizures. Its radiological signs can be observed in grey and white matter at the posterior region of the cerebral hemispheres. HSP should be considered in children with PRES in the presence of rash, joint and gastrointestinal symptoms. We reported a 5-year-old patient who developed acute renal failure and PRES by reason of HSP. PMID:23946524

  18. [Progressive multifocal encephalopathy in a LED patient].

    PubMed

    Tikkakoski, Tapani; Ingo, Sinikka; Julin, Lillemor; Kanckos, Sven

    2015-01-01

    Progressive multifocal encephalopathy (PML) is a rare demyelinating disease of the central nervous system, caused by the reactivation of the JC virus in the body during immunosuppression. The use of monoclonal antibodies predisposes to PML, and the epidemiology of the disease has changed. We describe the first PML published from Finland and associated with rituximab treatment in a LED patient.

  19. Phenytoin-induced encephalopathy in a child

    PubMed Central

    Mehndiratta, Sumit

    2016-01-01

    Phenytoin is a commonly used antiepileptic medication in the pediatric age group, but it has a narrow therapeutic range. Various adverse effects have been reported commonly. We report a relatively rare case of encephalopathy in a child from overdose of injectable phenytoin due to ignorance of the previous treatment. Scrutiny of medical records and history is of utmost importance while administering such medications.

  20. PRIONS AND THE TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES

    EPA Science Inventory

    This book chapter is an invited, scholarly review of the mechanism(s) of TSEs for the 2nd edition of Metabolic Encephalopathies. Each chapter in the book assumes a professional knowledge of neuroscience and biochemistry, and the focus of the book is on the metabolic basis of dise...

  1. The transmissible spongiform encephalopathies of livestock.

    PubMed

    Greenlee, Justin J; Greenlee, M Heather West

    2015-01-01

    Prion diseases or transmissible spongiform encephalopathies (TSEs) are fatal protein-misfolding neurodegenerative diseases. TSEs have been described in several species, including bovine spongiform encephalopathy (BSE) in cattle, scrapie in sheep and goats, chronic wasting disease (CWD) in cervids, transmissible mink encephalopathy (TME) in mink, and Kuru and Creutzfeldt-Jakob disease (CJD) in humans. These diseases are associated with the accumulation of a protease-resistant, disease-associated isoform of the prion protein (called PrP(Sc)) in the central nervous system and other tissues, depending on the host species. Typically, TSEs are acquired through exposure to infectious material, but inherited and spontaneous TSEs also occur. All TSEs share pathologic features and infectious mechanisms but have distinct differences in transmission and epidemiology due to host factors and strain differences encoded within the structure of the misfolded prion protein. The possibility that BSE can be transmitted to humans as the cause of variant Creutzfeldt-Jakob disease has brought attention to this family of diseases. This review is focused on the TSEs of livestock: bovine spongiform encephalopathy in cattle and scrapie in sheep and goats.

  2. The transmissible spongiform encephalopathies of livestock.

    PubMed

    Greenlee, Justin J; Greenlee, M Heather West

    2015-01-01

    Prion diseases or transmissible spongiform encephalopathies (TSEs) are fatal protein-misfolding neurodegenerative diseases. TSEs have been described in several species, including bovine spongiform encephalopathy (BSE) in cattle, scrapie in sheep and goats, chronic wasting disease (CWD) in cervids, transmissible mink encephalopathy (TME) in mink, and Kuru and Creutzfeldt-Jakob disease (CJD) in humans. These diseases are associated with the accumulation of a protease-resistant, disease-associated isoform of the prion protein (called PrP(Sc)) in the central nervous system and other tissues, depending on the host species. Typically, TSEs are acquired through exposure to infectious material, but inherited and spontaneous TSEs also occur. All TSEs share pathologic features and infectious mechanisms but have distinct differences in transmission and epidemiology due to host factors and strain differences encoded within the structure of the misfolded prion protein. The possibility that BSE can be transmitted to humans as the cause of variant Creutzfeldt-Jakob disease has brought attention to this family of diseases. This review is focused on the TSEs of livestock: bovine spongiform encephalopathy in cattle and scrapie in sheep and goats. PMID:25991695

  3. Psychometric tests for diagnosing minimal hepatic encephalopathy.

    PubMed

    Weissenborn, Karin

    2013-06-01

    While it is consensus that minimal hepatic encephalopathy (mHE) has significant impact on a patient's daily living, and thus should be diagnosed and treated, there is no consensus about the optimal diagnostic tools. At present the most frequently used psychometric methods for diagnosing minimal hepatic encephalopathy are the Inhibitory Control Test and the Psychometric Hepatic Encephalopathy Score PHES. Another frequently used method is Critical Flicker Frequency. The PHES and the Repeatable Battery for the Assessment of Neuropsychological Status have been recommended for diagnosing mHE by a working party commissioned by the International Society for Hepatic Encephalopathy and Nitrogen Metabolism. Recently the Continuous Reaction Time Test, which has been used in the 1980ies, has gained new interest. Today, no data are available that allow to decide which of these methods is the most appropriate. In fact, even basic information such as dependence on age, sex and education or influence of diseases that frequently accompany liver cirrhosis upon test results is missing for most of them. Future studies must address these questions to improve diagnosis of mHE. PMID:22993201

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

    PubMed

    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.

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

    SciTech Connect

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

    1991-03-01

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

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

    PubMed Central

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

    2015-01-01

    Myocardial injury because of oxidative stress manifesting through reductions in left ventricular ejection fraction (LVEF) may occur after the administration of anthracycline-based chemotherapy (A-bC). We hypothesized that bilirubin, an effective endogenous antioxidant, may attenuate the reduction in LVEF that sometimes occurs after receipt of A-bC. We identified 751 consecutively treated patients with cancer who underwent a pre-A-bC LVEF measurement, exhibited a serum total bilirubin level <2 mg/dl, and then received a post-A-bC LVEF assessment because of symptomatology associated with heart failure. Analysis of variance, Tukey’s Studentized range test, and chi-square tests were used to evaluate an association between bilirubin and LVEF changes. The LVEF decreased by 10.7 ± 13.7%, 8.9 ± 11.8%, and 7.7 ± 11.5% in group 1 (bilirubin at baseline ≤0.5 mg/dl), group 2 (bilirubin 0.6 to 0.8 mg/dl), and group 3 (bilirubin 0.9 to 1.9 mg/dl), respectively. More group 1 patients experienced >15% decrease in LVEF compared with those in group 3 (p = 0.039). After adjusting for age, coronary artery disease/myocardial infarction, diabetes mellitus, hematocrit, and the use of cardioactive medications, higher precancer treatment bilirubin levels and lesser total anthracycline doses were associated with LVEF preservation (p =0.047 and 0.011, respectively). In patients treated with anthracyclines who subsequently develop symptoms associated with heart failure, pre-anthracycline treatment serum bilirubin levels inversely correlate with subsequent deterioration in post-cancer treatment LVEF. In conclusion, these results suggest that increased levels of circulating serum total bilirubin, an intrinsic antioxidant, may facilitate preservation of LVEF in patients receiving A-bC for cancer. PMID:26433273

  7. Pathogenesis of hepatic encephalopathy: role of ammonia and systemic inflammation.

    PubMed

    Aldridge, Dominic R; Tranah, Edward J; Shawcross, Debbie L

    2015-03-01

    The syndrome we refer to as Hepatic Encephalopathy (HE) was first characterized by a team of Nobel Prize winning physiologists led by Pavlov and Nencki at the Imperial Institute of Experimental Medicine in Russia in the 1890's. This focused upon the key observation that performing a portocaval shunt, which bypassed nitrogen-rich blood away from the liver, induced elevated blood and brain ammonia concentrations in association with profound neurobehavioral changes. There exists however a spectrum of metabolic encephalopathies attributable to a variety (or even absence) of liver hepatocellular dysfunctions and it is this spectrum rather than a single disease entity that has come to be defined as HE. Differences in the underlying pathophysiology, treatment responses and outcomes can therefore be highly variable between acute and chronic HE. The term also fails to articulate quite how systemic the syndrome of HE can be and how it can be influenced by the gastrointestinal, renal, nervous, or immune systems without any change in background liver function. The pathogenesis of HE therefore encapsulates a complex network of interdependent organ systems which as yet remain poorly characterized. There is nonetheless a growing recognition that there is a complex but influential synergistic relationship between ammonia, inflammation (sterile and non-sterile) and oxidative stress in the pathogenesis HE which develops in an environment of functional immunoparesis in patients with liver dysfunction. Therapeutic strategies are thus moving further away from the traditional specialty of hepatology and more towards novel immune and inflammatory targets which will be discussed in this review. PMID:26041962

  8. Recurrent encephalopathy? No I'm a sleeping beauty!

    PubMed

    Iqbal, Mehtab; Prasad, Manish; Ritey, Christopher

    2014-01-01

    To describe the clinical presentation of 'Kleine-Levin (sleeping beauty) syndrome' in a child, who presented with recurrent episodes consistent with encephalopathy, associated with excessive sleepiness, cognitive and behavioural disturbance and hyper sexuality. 14 years old boy presented acutely with excessive tiredness, sleeping excessively, abnormal behaviour and hypersexuality following a viral throat infection. On examination he was sleepy but easily arousable. His GCS (15/15) and rest of the neurological examination including fundoscopy and other systemic examination was completely unremarkable. All his initial investigations including electrolytes, LFTs, CSF, virology screen and MRI brain scan were normal. Detailed autoimmune screening was also negative. EEG showed non-specific diffuse slowing consistent with encephalopathy. His excessive sleepiness gradually improved together with his altered behaviour in about two weeks after presentation. Hyper sexuality became more overt during this phase. All these symptoms completely disappeared three weeks after his presentation and he attended school as before. He was readmitted six weeks later with exactly similar presentation and again only positive result being diffuse non-specific slowing of EEG. His recovery was also similar and he was completely back to his normal self in three weeks time. His recurrent symptoms were consistent with 'Kleine-Levin syndrome (KLS)' or 'sleeping beauty syndrome'. KLS is a rare disorder which mainly affects adolescent males. Common symptoms include hypersomnia (100%), cognitive changes (96%), eating disturbances (80%), hypersexuality, compulsions, and depressed mood. The syndrome usually lasts for 8 years, with on an average seven episode of 10 days each recurring every 3.5 months. It is most frequently precipitated by infections and somnolence decreases using stimulants in nearly 40% of cases.

  9. Recurrent encephalopathy? No I’m a sleeping beauty!

    PubMed Central

    Iqbal, Mehtab; Prasad, Manish; Ritey, Christopher

    2014-01-01

    To describe the clinical presentation of ‘Kleine-Levin (sleeping beauty) syndrome’ in a child, who presented with recurrent episodes consistent with encephalopathy, associated with excessive sleepiness, cognitive and behavioural disturbance and hyper sexuality. 14 years old boy presented acutely with excessive tiredness, sleeping excessively, abnormal behaviour and hypersexuality following a viral throat infection. On examination he was sleepy but easily arousable. His GCS (15/15) and rest of the neurological examination including fundoscopy and other systemic examination was completely unremarkable. All his initial investigations including electrolytes, LFTs, CSF, virology screen and MRI brain scan were normal. Detailed autoimmune screening was also negative. EEG showed non-specific diffuse slowing consistent with encephalopathy. His excessive sleepiness gradually improved together with his altered behaviour in about two weeks after presentation. Hyper sexuality became more overt during this phase. All these symptoms completely disappeared three weeks after his presentation and he attended school as before. He was readmitted six weeks later with exactly similar presentation and again only positive result being diffuse non-specific slowing of EEG. His recovery was also similar and he was completely back to his normal self in three weeks time. His recurrent symptoms were consistent with ‘Kleine-Levin syndrome (KLS)’ or ‘sleeping beauty syndrome’. KLS is a rare disorder which mainly affects adolescent males. Common symptoms include hypersomnia (100%), cognitive changes (96%), eating disturbances (80%), hypersexuality, compulsions, and depressed mood. The syndrome usually lasts for 8 years, with on an average seven episode of 10 days each recurring every 3.5 months. It is most frequently precipitated by infections and somnolence decreases using stimulants in nearly 40% of cases. PMID:24891916

  10. Pathogenesis of Hepatic Encephalopathy: Role of Ammonia and Systemic Inflammation

    PubMed Central

    Aldridge, Dominic R.; Tranah, Edward J.; Shawcross, Debbie L.

    2015-01-01

    The syndrome we refer to as Hepatic Encephalopathy (HE) was first characterized by a team of Nobel Prize winning physiologists led by Pavlov and Nencki at the Imperial Institute of Experimental Medicine in Russia in the 1890's. This focused upon the key observation that performing a portocaval shunt, which bypassed nitrogen-rich blood away from the liver, induced elevated blood and brain ammonia concentrations in association with profound neurobehavioral changes. There exists however a spectrum of metabolic encephalopathies attributable to a variety (or even absence) of liver hepatocellular dysfunctions and it is this spectrum rather than a single disease entity that has come to be defined as HE. Differences in the underlying pathophysiology, treatment responses and outcomes can therefore be highly variable between acute and chronic HE. The term also fails to articulate quite how systemic the syndrome of HE can be and how it can be influenced by the gastrointestinal, renal, nervous, or immune systems without any change in background liver function. The pathogenesis of HE therefore encapsulates a complex network of interdependent organ systems which as yet remain poorly characterized. There is nonetheless a growing recognition that there is a complex but influential synergistic relationship between ammonia, inflammation (sterile and non-sterile) and oxidative stress in the pathogenesis HE which develops in an environment of functional immunoparesis in patients with liver dysfunction. Therapeutic strategies are thus moving further away from the traditional specialty of hepatology and more towards novel immune and inflammatory targets which will be discussed in this review. PMID:26041962

  11. Food Safety: Bovine Spongiform Encephalopathy (Mad Cow Disease).

    PubMed

    Acheson, David W. K.

    2002-01-01

    Bovine spongiform encephalopathy is just one of a group of diseases known as transmissible spongiform encephalopathies. Only recently has it become recognized that transmissible spongiform encephalopathies are likely due to proteins known as prions. Although it has been recognized that transmissible spongiform encephalopathies may readily spread within species, the recent observations that bovine spongiform encephalopathy in cattle may have originated from another transmissible spongiform encephalopathy in sheep, known as scrapie, is cause for concern. Further, bovine spongiform encephalopathy has now been strongly linked with a universally fatal human neurologic disease known as new variant Creutzfeldt-Jakob disease. Currently the only approach to preventing bovine spongiform encephalopathy, and subsequent new variant Creutzfeldt-Jakob disease in humans, from ingestion of bovine spongiform encephalopathy-infected material is to avoid consumption of contaminated food. Little can be done to treat food that will destroy prions and leave a palatable product. At this stage we are continuing to learn about transmissible spongiform encephalopathies and their implications on human health. This is an ever-changing situation and has an unpredictable element in terms of the extent of the current outbreaks in England and other parts of Europe. PMID:11984426

  12. Unconjugated bilirubin effect on 3H-ouabain binding to human fetal red cells.

    PubMed

    Corchs, J L; Corchs, M J; Serrani, R E

    1994-03-01

    Human fetal red cells show heterogeneity of 3H-ouabain binding sites. These cells were chosen as a model to look into unconjugated bilirubin effects on the primary active Na(+)-K+ transport mechanism. Evidences are presented suggesting that unconjugated bilirubin affects 3H-ouabain binding but not through a direct effect. This is supported by the fact that the "low affinity" subgroup sites of the last mentioned ligand persists after unconjugated bilirubin treatment of cells, whereas the "high-affinity" subgroup disappears.

  13. Patients with acute liver failure listed for superurgent liver transplantation in France: reevaluation of the Clichy-Villejuif criteria.

    PubMed

    Ichai, Philippe; Legeai, Camille; Francoz, Claire; Boudjema, Karim; Boillot, Olivier; Ducerf, Christian; Mathurin, Philippe; Pruvot, François-René; Suc, Bertrand; Wolf, Philippe; Soubrane, Olivier; Le Treut, Yves Patrice; Cherqui, Daniel; Hannoun, Laurent; Pageaux, Georges-Philippe; Gugenheim, Jean; Letoublon, Christian; Saric, Jean; Di Martino, Vincent; Abergel, Armand; Chiche, Laurence; Antonini, Teresa Maria; Jacquelinet, Christian; Castaing, Denis; Samuel, Didier

    2015-04-01

    In France, decisions regarding superurgent (SU) liver transplantation (LT) for patients with acute liver failure (ALF) are principally based on the Clichy-Villejuif (CV) criteria. The aims of the present study were to study the outcomes of patients registered for SU LT and the factors that were predictive of spontaneous improvement and to determine the usefulness of the CV criteria. All patients listed in France for SU LT between 1997 and 2010 who were 15 years old or older with ALF were included. In all, 808 patients were listed for SU transplantation: 22% with paracetamol-induced ALF and 78% with non-paracetamol-induced ALF. Of these 808 patients, 112 improved spontaneously, 587 underwent LT, and 109 died or left the waiting list because of a worsening condition. The 1-year survival rate according to an intention-to-treat analysis and the survival after LT were 66.3% [interquartile range (IQR), 62.7%-69.7%] and 74.2% (IQR, 70.5%-77.6%), respectively. The factors that were predictive of a spontaneous recovery with ALF-related paracetamol hepatotoxicity were as follows: hepatic encephalopathy grade 0, 1, or 2 [odds ratio (OR), 4.8; 95% confidence interval (CI), 1.99-11.6]; creatinine clearance≥60 mL/minute/1.73 m2 (OR, 4.77; 95% CI, 1.96-11.63), a bilirubin level<200 µmol/L (OR, 21.64; 95% CI, 1.76-265.7); and a factor V level>20% (OR, 5.79; 95% CI, 1.66-20.29). For ALF-related nonparacetamol hepatotoxicity, the factor that was predictive of a spontaneous recovery was a bilirubin level<200 µmol/L (OR, 10.38; 95% CI, 4.71-22.86). The sensitivity, specificity, and positive and negative predictive values for the CV criteria were 75%, 56%, 50%, and 79%, respectively, for ALF due to paracetamol and 69%, 50%, 64%, and 55%, respectively, for ALF not related to paracetamol. The performance of current criteria for SU transplantation could be improved if paracetamol-induced ALF and non-paracetamol-induced ALF were split and 2 other items were included in this model: the

  14. The cytotoxic effect of unconjugated bilirubin in human neuroblastoma SH-SY5Y cells is modulated by the expression level of MRP1 but not MDR1.

    PubMed

    Corich, Lucia; Aranda, Alejandro; Carrassa, Laura; Bellarosa, Cristina; Ostrow, J Donald; Tiribelli, Claudio

    2009-01-01

    In vitro and in vivo studies have demonstrated that UCB (unconjugated bilirubin) is neurotoxic. Although previous studies suggested that both MRP1 (multidrug resistance-associated protein 1) and MDR1 (multidrug resistance protein 1) may protect cells against accumulation of UCB, direct comparison of their role in UCB transport was never performed. To this end, we used an inducible siRNA (small interfering RNA) expression system to silence the expression of MRP1 and MDR1 in human neuroblastoma SH-SY5Y cells. The effects of in vitro exposure to clinically-relevant levels of unbound UCB were compared between unsilenced (control) cells and cells with similar reductions in the expression of MRP1 or MDR1, documented by RT-PCR (reverse transcription-PCR) (mRNA), immunoblotting (protein), and for MDR1, the enhanced net uptake of a specific fluorescent substrate. Cytotoxicity was assessed by the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide] test. MRP1-deficient cells accumulated significantly more UCB and suffered greater cytotoxicity than controls. By contrast, MDR1-deficient cells exhibited UCB uptake and cytotoxicity comparable with controls. At intermediate levels of silencing, the increased susceptibility to UCB toxicity closely correlated with the decrease in the expression of MRP1, but not of MDR1. These data support the concept that limitation of cellular UCB accumulation, due to UCB export mediated by MRP1, but not MDR1, plays an important role in preventing bilirubin encephalopathy in the newborn.

  15. Physical measurements of Cu{sup 2+}-complexes of bilirubin

    SciTech Connect

    Ferraro, J.R.; Wu, J.G.; Li, W.H.; Xu, Y.Z.; Xu, D.F.; Shen, G.R.; Soloway, R.D.

    1995-12-31

    Copper is known to form complexes with bilirubin (H{sub 2}BR). Such complexes have received increased attention due to their clinical significance as free-radical scavengers. The purpose of this study was to examine a series of Cu{sup 2+}BR complexes to ascertain the nature of the binding between Cu{sup 2+} and BR. Several physical measurements of the salts were made, such as Fourier Transform Infrared (FT-IR), Fourier Transform Raman spectroscopy (FT-R), and Electron Paramagnetic Resonance (EPR). The complexes were prepared by dissolving protonated BR in NaOH, and adding different ratios of aqueous CuCl{sub 2}. At ratios of Cu{sup 2+}:H{sub 2}BR of 1:1 and 2:1, soluble complexes were formed. In solution EPR spectra demonstrated 9 hyperfine peaks, which from the splitting, is indicative of Cu{sup 2+} coordinated to 4 nitrogen atoms coming from 2 molecules of BR.

  16. 76 FR 38667 - Transmissible Spongiform Encephalopathies Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-01

    ... HUMAN SERVICES Food and Drug Administration Transmissible Spongiform Encephalopathies Advisory Committee... be open to the public. Name of Committee: Transmissible Spongiform Encephalopathies Advisory... available at the following link. Transmissible Spongiform Encephalopathies Advisory Committee...

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

    PubMed

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

    2015-04-01

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

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

    PubMed

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

    2015-04-01

    Neonatal encephalopathy, a clinical syndrome affecting term-born and late preterm newborn infants, increases the risk of perinatal death and long-term neurological morbidity, especially cerebral palsy. With the advent of therapeutic hypothermia, a treatment designed for hypoxic or ischaemic injury, associated mortality and morbidity rates have decreased. Unfortunately, only about one in eight neonates (95% confidence interval) who meet eligibility criteria for therapeutic cooling apparently benefit from the treatment. Studies of infants in representative populations indicate that neonatal encephalopathy is a potential result of a variety of antecedents and that asphyxial complications at birth account for only a small percentage of neonatal encephalopathy. In contrast, clinical case series suggest that a large proportion of neonatal encephalopathy is hypoxic or ischaemic, and trials of therapeutic hypothermia are specifically designed to include only infants exposed to hypoxia or ischaemia. This review addresses the differences, definitional and methodological, between infants studied and investigations undertaken, in population studies compared with cooling trials. It raises the question if there may be subgroups of infants with a clinical diagnosis of hypoxic-ischaemic encephalopathy (HIE) in whom the pathobiology of neonatal neurological depression is not fundamentally hypoxic or ischaemic and, therefore, for whom cooling may not be beneficial. In addition, it suggests approaches to future trials of cooling plus adjuvant therapy that may contribute to further improvement of care for these vulnerable neonates. PMID:25800486

  19. [Role of bilirubin in the prevention of cardiovascular diseases and cancer].

    PubMed

    Vítek, Libor

    2016-01-01

    Oxidative stress contributes importantly to pathogenesis of numerous civilization diseases, including cardiovascular diseases, cancer, as well as autoimmune and neurodegenerative conditions. Bilirubin is the major product of the heme catabolic pathway in the intravascular compartment. For long time, bilirubin was considered to be only a waste product, however, recent data from the last two decades have proved its important protective properties, which contributes to defense against development of civilization diseases. Numerous experimental as well as clinical studies have demonstrated association between low bilirubin concentrations and cardiovascular diseases, as well as certain cancers. On the other hand, subjects with mildly elevated blood bilirubin levels, typical for Gilbert syndrome, have decreased risk of these diseases. PMID:27088786

  20. Hashimoto's encephalopathy: A rare proteiform disorder.

    PubMed

    Montagna, Giacomo; Imperiali, Mauro; Agazzi, Pamela; D'Aurizio, Federica; Tozzoli, Renato; Feldt-Rasmussen, Ulla; Giovanella, Luca

    2016-05-01

    Hashimoto's encephalopathy (HE) is a rare not well understood, progressive and relapsing multiform disease, characterized by seizures, movement disorders, subacute cognitive dysfunction, psychiatric symptoms and responsiveness to steroid therapy. The disorder is generally associated with thyroid diseases and the most common feature is the presence of anti-thyroperoxidase antibodies (TPOAb). Patients are usually euthyroid or mildly hypothyroid at presentation. All age groups can be affected. The pathophysiology is still unclear, especially the link between elevated serum TPOAb and the encephalopathy. Most reported cases occurred in women and girls. Unspecific symptoms, non-pathognomonic laboratory neurophysiology and neuroimaging features make its diagnosis a real challenge for clinicians. The case of a 16 year old boy, with a clinical picture of HE associated with hypothyroidism, demonstrating an excellent response to high dose steroids is presented together with a systematic review of the literature. PMID:26849953

  1. Hepatic encephalopathy after treatment with temozolomide.

    PubMed

    Goldbecker, Annemarie; Tryc, Anita Blanka; Raab, Peter; Worthmann, Hans; Herrmann, Julian; Weissenborn, Karin

    2011-05-01

    Temozolomide in combination with radiation has been in use for more than 5 years for the therapy of glioblastoma. Known adverse effects concerning the gastrointestinal system are elevation of liver enzymes. We present the case of a patient treated with temozolomide who developed severe cholestatic liver damage and consecutive hepatic encephalopathy. Neurological symptoms were mistaken as being caused by focal brain damage for more than 9 months. After the correct diagnosis had been made and the treatment had been started, the patient's condition ameliorated. In conclusion, neurological deficits in patients with known brain lesion should not be attributed automatically to the pre-existing damage even if it is progressive but should be examined carefully, also including toxic and metabolic encephalopathies into the differential diagnosis. Furthermore, new side effects of drugs have to be considered. At least this case might lead to a closer monitoring of liver enzymes during temozolomide therapy.

  2. [Metabolic encephalopathy secondary to vitamin D intoxication].

    PubMed

    Herrera Martínez, Aura; Viñals Torràs, Montserrat; Muñoz Jiménez, Ma Concepción; Arenas de Larriva, Antonio Pablo; Molina Puerta, Ma José; Manzano García, Gregorio; Gálvez Moreno, Ma Ángeles; Calañas-Continente, Alfonso

    2014-10-25

    The association between vitamin D deficiency and increased risk of, among others, cardiovascular and autoimmune diseases has lead in the last years to an enhanced interest in the usage of supplements to achieve the normalization of plasmatic values at 25(OH) D. Apparently this search for normalization is resulting in an higher incidence on vitamin D intoxication. We present the case of an 81 years old woman with metabolic encephalopathy and renal failure secondary to iatrogenic vitamin D intoxication. Calcium and vitamin D oral supplements were prescribed after an osteoporotic vertebral fracture. The patient improved clinically as well as analytically after receiving treatment with diuretics and hydration. We emphasize the importance of discarding hypercalcemia as a cause of metabolic encephalopathy; moreover we highly recommend keeping vitamin D intoxication in mind as an uncommon although always possible etiology of reversible hypercalcemia and renal failure.

  3. Head stereotypies in STXBP1 encephalopathy.

    PubMed

    Kim, Young Ok; Korff, Christian M; Villaluz, Mel Michel G; Suls, Arvid; Weckhuysen, Sarah; De Jonghe, Peter; Scheffer, Ingrid E

    2013-08-01

    STXBP1 encephalopathy is associated with a range of movement disorders. We observed head stereotypies in three patients. These comprised a slow (<1Hz), high-amplitude, horizontal, 'figure-of-eight' pattern, beginning at age 4-6 years and resulting in neck muscle hypertrophy, in two males; a faster (2-3Hz), side-to-side, 'no' movement, starting at the age of 9 years 6 months was observed in one female. Upper limb and truncal stereotypies and vocalization occurred intermittently with the head movements. The stereotypies increased with excitement but settled with concentration and sleep. Head and upper limb stereotypies are valuable clinical clues to the diagnosis of STXBP1 encephalopathy in patients with profound impairments.

  4. Normal coordinate analysis of bilirubin vibrational spectra: Effects of intramolecular hydrogen bonding

    NASA Astrophysics Data System (ADS)

    Yang, Bijun; Taylor, Robert C.; Morris, Michael D.; Wang, Xiu-Zhen; Wu, Jin-guang; Yu, Bao-Zhu; Xu, Guang-xian; Soloway, Roger D.

    1993-11-01

    Normal coordinate analyses are presented for half-bilirubin molecules. Calculations for the AB pyrromethenone include intramolecular hydrogen bonds, while those for the CD chromophore exclude intramolecular hydrogen bonds. Valence force-field parameters have been optimized to correlate closely with the IR and Raman spectra of the target molecules. The results of the calculations are compared with the spectra of bilirubin IXa and various model compounds in the solid state and solution.

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

    PubMed Central

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

    2016-01-01

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

  6. Bilirubin UDP-glucuronosyltransferase 1A1 gene polymorphisms: susceptibility to oxidative damage and cancer?

    PubMed

    Grant, D J; Bell, D A

    2000-12-01

    The UDP-glucuronosyltransferase 1A1 (UGT1A1) gene product catalyzes the glucuronidation of serum bilirubin as part of normal heme catabolism. Recently, TA repeat polymorphisms containing five, six, seven, and eight TA dinucleotides in a putative TATA box in the promoter region of the UGT1A1 gene have been described. TA repeat number modulates UGT1A1 transcriptional activity and the quantity of enzyme available to conjugate serum bilirubin. Serum bilirubin is a known antioxidant, and low serum bilirubin has been associated with increased risk for coronary artery disease and inhibition of reactive oxygen species (ROS)-induced damage to erythrocytes in vitro. We hypothesize that the UGT1A1 TA repeats or other functional polymorphisms resulting in lower serum bilirubin levels may be predictive of genetic susceptibility to oxidative damage and cancer. Exposure-related or endogenous production of ROS may impact the integrity of cellular macromolecules and infrastructure, lead to DNA base changes or chromosomal aberrations, and induce toxicity or apoptosis. ROS damage to lipoproteins may be a factor in formation of atherogenic plaques in coronary heart disease. Thus, cellular oxidative stress could contribute to tumorigenesis through mutagenic or epigenetic pathways, and higher serum bilirubin levels should inhibit this process. No definitive studies have been performed, but in a small prospective study of colon cancer, serum bilirubin levels were observed to be lower in these cases. Another study has suggested a link between UGT1A1 alleles, estrogen metabolism, and risk in breast cancer. Epidemiologic studies examining variation in ROS metabolism, ROS damage, bilirubin, and cancer risk will demonstrate the value of this hypothesis. PMID:11170257

  7. Transmissible Spongiform Encephalopathy and Meat Safety

    NASA Astrophysics Data System (ADS)

    Ward, Hester J. T.; Knight, Richard S. G.

    Prion diseases or transmissible spongiform encephalopathies (TSEs) comprise a wide-ranging group of neurodegenerative diseases found in animals and humans. They have diverse causes and geographical distributions, but have similar pathological features, transmissibility and, are ultimately, fatal. Central to all TSEs is the presence of an abnormal form of a normal host protein, namely the prion protein. Because of their potential transmissibility, these diseases have wide public health ramifications.

  8. The Role of the Neurointensive Care Nursery for Neonatal Encephalopathy.

    PubMed

    Glass, Hannah C; Rowitch, David H

    2016-09-01

    Neonatal encephalopathy due to intrapartum events is estimated at 1 to 2 per 1000 live births in high-income countries. Outcomes have improved over the past decade due to implementation of therapeutic hypothermia, the only clinically available neuroprotective strategy for hypoxic-ischemic encephalopathy. Neonatal encephalopathy is the most common condition treated within a neonatal neurocritical care unit. Neonates with encephalopathy benefit from a neurocritical care approach due to prevention of secondary brain injury through attention to basic physiology, earlier recognition and treatment of neurologic complications, consistent management using guidelines and protocols, and use of optimized teams at dedicated referral centers. PMID:27524453

  9. De novo mutations in epileptic encephalopathies.

    PubMed

    Allen, Andrew S; Berkovic, Samuel F; Cossette, Patrick; Delanty, Norman; Dlugos, Dennis; Eichler, Evan E; Epstein, Michael P; Glauser, Tracy; Goldstein, David B; Han, Yujun; Heinzen, Erin L; Hitomi, Yuki; Howell, Katherine B; Johnson, Michael R; Kuzniecky, Ruben; Lowenstein, Daniel H; Lu, Yi-Fan; Madou, Maura R Z; Marson, Anthony G; Mefford, Heather C; Esmaeeli Nieh, Sahar; O'Brien, Terence J; Ottman, Ruth; Petrovski, Slavé; Poduri, Annapurna; Ruzzo, Elizabeth K; Scheffer, Ingrid E; Sherr, Elliott H; Yuskaitis, Christopher J; Abou-Khalil, Bassel; Alldredge, Brian K; Bautista, Jocelyn F; Berkovic, Samuel F; Boro, Alex; Cascino, Gregory D; Consalvo, Damian; Crumrine, Patricia; Devinsky, Orrin; Dlugos, Dennis; Epstein, Michael P; Fiol, Miguel; Fountain, Nathan B; French, Jacqueline; Friedman, Daniel; Geller, Eric B; Glauser, Tracy; Glynn, Simon; Haut, Sheryl R; Hayward, Jean; Helmers, Sandra L; Joshi, Sucheta; Kanner, Andres; Kirsch, Heidi E; Knowlton, Robert C; Kossoff, Eric H; Kuperman, Rachel; Kuzniecky, Ruben; Lowenstein, Daniel H; McGuire, Shannon M; Motika, Paul V; Novotny, Edward J; Ottman, Ruth; Paolicchi, Juliann M; Parent, Jack M; Park, Kristen; Poduri, Annapurna; Scheffer, Ingrid E; Shellhaas, Renée A; Sherr, Elliott H; Shih, Jerry J; Singh, Rani; Sirven, Joseph; Smith, Michael C; Sullivan, Joseph; Lin Thio, Liu; Venkat, Anu; Vining, Eileen P G; Von Allmen, Gretchen K; Weisenberg, Judith L; Widdess-Walsh, Peter; Winawer, Melodie R

    2013-09-12

    Epileptic encephalopathies are a devastating group of severe childhood epilepsy disorders for which the cause is often unknown. Here we report a screen for de novo mutations in patients with two classical epileptic encephalopathies: infantile spasms (n = 149) and Lennox-Gastaut syndrome (n = 115). We sequenced the exomes of 264 probands, and their parents, and confirmed 329 de novo mutations. A likelihood analysis showed a significant excess of de novo mutations in the ∼4,000 genes that are the most intolerant to functional genetic variation in the human population (P = 2.9 × 10(-3)). Among these are GABRB3, with de novo mutations in four patients, and ALG13, with the same de novo mutation in two patients; both genes show clear statistical evidence of association with epileptic encephalopathy. Given the relevant site-specific mutation rates, the probabilities of these outcomes occurring by chance are P = 4.1 × 10(-10) and P = 7.8 × 10(-12), respectively. Other genes with de novo mutations in this cohort include CACNA1A, CHD2, FLNA, GABRA1, GRIN1, GRIN2B, HNRNPU, IQSEC2, MTOR and NEDD4L. Finally, we show that the de novo mutations observed are enriched in specific gene sets including genes regulated by the fragile X protein (P < 10(-8)), as has been reported previously for autism spectrum disorders.

  10. Extending the KCNQ2 encephalopathy spectrum

    PubMed Central

    Weckhuysen, Sarah; Ivanovic, Vanja; Hendrickx, Rik; Van Coster, Rudy; Hjalgrim, Helle; Møller, Rikke S.; Grønborg, Sabine; Schoonjans, An-Sofie; Ceulemans, Berten; Heavin, Sinead B.; Eltze, Christin; Horvath, Rita; Casara, Gianluca; Pisano, Tiziana; Giordano, Lucio; Rostasy, Kevin; Haberlandt, Edda; Albrecht, Beate; Bevot, Andrea; Benkel, Ira; Syrbe, Steffan; Sheidley, Beth; Guerrini, Renzo; Poduri, Annapurna; Lemke, Johannes R.; Mandelstam, Simone; Scheffer, Ingrid; Angriman, Marco; Striano, Pasquale; Marini, Carla; Suls, Arvid

    2013-01-01

    Objectives: To determine the frequency of KCNQ2 mutations in patients with neonatal epileptic encephalopathy (NEE), and to expand the phenotypic spectrum of KCNQ2 epileptic encephalopathy. Methods: Eighty-four patients with unexplained NEE were screened for KCNQ2 mutations using classic Sanger sequencing. Clinical data of 6 additional patients with KCNQ2 mutations detected by gene panel were collected. Detailed phenotyping was performed with particular attention to seizure frequency, cognitive outcome, and video-EEG. Results: In the cohort, we identified 9 different heterozygous de novo KCNQ2 missense mutations in 11 of 84 patients (13%). Two of 6 missense mutations detected by gene panel were recurrent and present in patients of the cohort. Seizures at onset typically consisted of tonic posturing often associated with focal clonic jerking, and were accompanied by apnea with desaturation. One patient diagnosed by gene panel had seizure onset at the age of 5 months. Based on seizure frequency at onset and cognitive outcome, we delineated 3 clinical subgroups, expanding the spectrum of KCNQ2 encephalopathy to patients with moderate intellectual disability and/or infrequent seizures at onset. Recurrent mutations lead to relatively homogenous phenotypes. One patient responded favorably to retigabine; 5 patients had a good response to carbamazepine. In 6 patients, seizures with bradycardia were recorded. One patient died of probable sudden unexpected death in epilepsy. Conclusion: KCNQ2 mutations cause approximately 13% of unexplained NEE. Patients present with a wide spectrum of severity and, although rare, infantile epilepsy onset is possible. PMID:24107868

  11. Blood Biomarkers for Evaluation of Perinatal Encephalopathy

    PubMed Central

    Graham, Ernest M.; Burd, Irina; Everett, Allen D.; Northington, Frances J.

    2016-01-01

    Recent research in identification of brain injury after trauma shows many possible blood biomarkers that may help identify the fetus and neonate with encephalopathy. Traumatic brain injury shares many common features with perinatal hypoxic-ischemic encephalopathy. Trauma has a hypoxic component, and one of the 1st physiologic consequences of moderate-severe traumatic brain injury is apnea. Trauma and hypoxia-ischemia initiate an excitotoxic cascade and free radical injury followed by the inflammatory cascade, producing injury in neurons, glial cells and white matter. Increased excitatory amino acids, lipid peroxidation products, and alteration in microRNAs and inflammatory markers are common to both traumatic brain injury and perinatal encephalopathy. The blood-brain barrier is disrupted in both leading to egress of substances normally only found in the central nervous system. Brain exosomes may represent ideal biomarker containers, as RNA and protein transported within the vesicles are protected from enzymatic degradation. Evaluation of fetal or neonatal brain derived exosomes that cross the blood-brain barrier and circulate peripherally has been referred to as the “liquid brain biopsy.” A multiplex of serum biomarkers could improve upon the current imprecise methods of identifying fetal and neonatal brain injury such as fetal heart rate abnormalities, meconium, cord gases at delivery, and Apgar scores. Quantitative biomarker measurements of perinatal brain injury and recovery could lead to operative delivery only in the presence of significant fetal risk, triage to appropriate therapy after birth and measure the effectiveness of treatment. PMID:27468268

  12. Using saccades to diagnose covert hepatic encephalopathy.

    PubMed

    Cunniffe, Nicholas; Munby, Henry; Chan, Shona; Saatci, Defne; Edison, Eric; Carpenter, R H S; Massey, Dunecan

    2015-06-01

    Covert Hepatic Encephalopathy (CHE), previously known as Minimal Hepatic Encephalopathy, is a subtle cognitive defect found in 30-70 % of cirrhosis patients. It has been linked to poor quality of life, impaired fitness to drive, and increased mortality: treatment is possible. Despite its clinical significance, diagnosis relies on psychometric tests that have proved unsuitable for use in a clinical setting. We investigated whether measurement of saccadic latency distributions might be a viable alternative. We collected data on 35 cirrhosis patients at Addenbrooke's Hospital, Cambridge, with no evidence of clinically overt encephalopathy, and 36 age-matched healthy controls. Performance on standard psychometric tests was evaluated to determine those patients with CHE as defined by the World Congress of Gastroenterology. We then compared visually-evoked saccades between those with CHE and those without, as well as reviewing blood test results and correlating saccadic latencies with biochemical parameters and prognostic scores. Cirrhosis patients have significantly longer median saccadic latencies than healthy controls. Those with CHE had significantly prolonged saccadic latencies when compared with those without CHE. Analysis of a cirrhosis patient's saccades can diagnose CHE with a sensitivity of 75 % and a specificity of 75 %. We concluded that analysis of a cirrhosis patient's saccadic latency distributions is a fast and objective measure that can be used as a diagnostic tool for CHE. This improved early diagnosis could direct avoidance of high-risk activities such as driving, and better inform treatment strategies. PMID:25586511

  13. Potential role of conjugated bilirubin and copper in the metabolism of lipid peroxides in bile.

    PubMed

    Stocker, R; Ames, B N

    1987-11-01

    Conjugated bilirubin and copper ions at their physiological concentrations in bile may play an important role in hydroperoxide and other detoxification. Conjugated bilirubin may also be an important chain-breaking antioxidant preventing lipid peroxidation. Bilirubin ditaurine (BR-DT), a water-soluble model compound of conjugated bilirubin, completely prevents the peroxyl radical-induced oxidation of phosphatidylcholine in either multilamellar liposomes or micelles. This antioxidant activity is associated with the bilirubin moiety of BR-DT, since taurine alone is inefficient in scavenging peroxyl radicals. The number of peroxyl radicals trapped per molecule of BR-DT is 1.9, compared to 4.7 trapped per molecule of biliverdin, the water-soluble physiological precursor of bilirubin. Peroxyl radical-induced oxidation of BR-DT results in a spectral shift in maximal absorbance toward shorter wavelengths; biliverdin is not formed as a major oxidation product. BR-DT, but neither taurine nor biliverdin, greatly accelerates the cupric ion-catalyzed decomposition of linoleic acid hydroperoxide. In the presence of ferric ion, BR-DT shows no lipid hydroperoxide-degrading activity. Addition of cupric ion to BR-DT results in formation of a complex with spectral features similar to that of a biliverdin-cupric ion complex, indicating that BR-DT and cupric ion undergo redox reactions.

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

    PubMed

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

    2014-02-01

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

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

    PubMed

    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

  16. A diazo-based dry film for determination of total bilirubin in serum.

    PubMed

    Dappen, G M; Sundberg, M W; Wu, T W; Babb, B E; Schaeffer, J R

    1983-01-01

    We have prepared a diazo-based dry film for use in determining total serum bilirubin. On a transparent support are a buffered gelatin layer containing a polymeric quaternary amine (the mordant) and a white, reflective spreading layer that contains all of the components necessary for detection of bilirubin. The method is based on the use of dyphylline and Triton X-100 surfactant to dissociate bilirubin from albumin and subsequent reaction of bilirubin with a diazonium salt [4-(N-carboxymethylsulfamyl)benzenediazonium hexafluorophosphate]. In the dry film, unconjugated, mono- and diconjugated, and strongly protein-linked (delta) bilirubin all react with the diazonium salt to produce azo dyes having absorption maxima at about 520 nm. With reflection densitometry and appropriate mathematical transformation, readings and bilirubin concentrations are linearly related to 260 mg/L. Results correlate well with those by the Jendrassik-Grof (Doumas modification) method (slope 0.994, intercept 1.1, correlation coefficient 0.993, Sy X x 4.0), and the method is precise (CV = 10.0% at Cav = 4.1 mg/L, 2.7% at Cav = 24.5 mg/L, 1.2% at Cav = 102 mg/L for patients' samples) and relatively free of interferences. PMID:6848278

  17. Dexmedetomidine controls twitch-convulsive syndrome in the course of uremic encephalopathy.

    PubMed

    Nomoto, Koichi; Scurlock, Corey; Bronster, David

    2011-12-01

    An 85 year old man with a history of chronic renal insufficiency was admitted to the cardiothoracic intensive care unit after aortic valve replacement. His postoperative course was marked by acute oliguric renal failure for high blood urea nitrogen (BUN) and acute hyperactive delirium. At this time he also developed tremors with muscle twitching; he received no other form of sedatives. A neurology consult made the diagnosis of twitch-convulsive syndrome associated with uremic encephalopathy. While the patient was receiving the dexmedetomidine infusion, the signs of the twitch-convulsive syndrome, particularly the twitching and tremors, disappeared. Within 30 minutes of the end of the dexmedetomidine infusion, symptoms of the twitch-convulsive syndrome returned, manifesting as acute tremulousness. After several dialysis treatments, his BUN decreased and the dexmedetomidine was weaned, without return of the symptoms of twitch-convulsive syndrome. PMID:22137518

  18. Genetics Home Reference: acute necrotizing encephalopathy type 1

    MedlinePlus

    ... interacts with a protein complex known as the nuclear pore. The nuclear pore is a channel that allows transport of ... transport of proteins and other molecules through the nuclear pore and helps modify proteins coming into or ...

  19. Encephalopathy in Acute Leukaemia Associated with Methotrexate Therapy

    PubMed Central

    Kay, H. E. M.; Knapton, P. J.; O'Sullivan, J. P.; Wells, D. G.; Harris, Ruth F.; Innes, Elizabeth M.; Stuart, J.; Schwartz, F. C. M.; Thompson, Eileen N.

    1972-01-01

    Seven patients are described in whom dementia developed during treatment with methotrexate for meningeal leukaemia. The patients presented with confusion, tremor, ataxia, irritability, and somnolence. There were major epileptic fits in two cases and in one case there was progression to coma and death. Necropsy findings in the latter showed infarcted areas in the temporal and parietal lobes, with no evidence of active leukaemic disease or of viral encephalitis. The condition has not responded to radiotherapy and no positive evidence of viral encephalitis has been obtained. On the other hand, when treated with folinic and folic acid the deterioration has been arrested and there has been some improvement; thus the condition appears to be due to methotrexate. The occurrence of so many cases within the past year of a condition not previously described is probably attributable to the introduction of intensive cytotoxic therapy directed against meningeal leukaemia. ImagesFIG. 2.FIG. 3.FIG. 4FIG. 5 PMID:4504035

  20. Estimation of unconjugated, conjugated, and "delta" bilirubin fractions in serum by use of two coated thin films.

    PubMed

    Sundberg, M W; Lauff, J J; Weiss, J S; Dappen, G M; Wu, T W; Spayd, R W; Seligson, D

    1984-08-01

    We used two coated thin films to measure the concentrations of unconjugated, conjugated, and total bilirubin as well as bilirubin covalently bound to albumin ("delta" bilirubin) in more than 400 serum samples. We measured the unconjugated and conjugated species by determining their reflection densities at two wavelengths (400 and 460 nm) on a coating designed for the enhanced spectral measurement of bilirubin but which does not register the delta form. Total bilirubin was measured by use of a diazo-based thin film (Clin Chem 29: 37-41, 1983). We estimated the concentration of delta bilirubin by subtracting the sum of unconjugated and conjugated bilirubin from the concentration of total bilirubin. All measurements agree well with those by comparative methods, as shown by linear regression. Slopes ranged from 0.92 to 1.02, correlation coefficients from 0.935 and 0.998. Linear combinations of these values can also be used to compute other results; e.g., the sum of conjugated and delta bilirubin can be considered to be an estimate of "direct"-reacting bilirubin. PMID:6744578

  1. Early detection of hepatic encephalopathy by recording visual evoked potential (VEP).

    PubMed

    Zamir, Doron; Storch, Shimon; Kovach, Ivan; Storch, Rita; Zamir, Chen

    2002-01-01

    The visual evoked potential (VEP) record in response to a pattern stimulus is a non invasive and reliable method of detecting central and peripheral nerve system abnormalities. VEP recording have been used in animals with fulminant hepatic failure, and also in-patients with hepatic encephalopathy and acute severe hepatitis. Our aims were: a. to evaluate the potency of PVEP in assessing hepatic encephalopathy. b. to find the rate of pathologic PVEP in patients with advanced liver cirrhosis. VEP was recorded in 14 chronic liver cirrhotic patients (6 alcoholic, 6 HCV-related, 2 cryptogenic) and 14 controls. Patients with any neurologic abnormalities were excluded from the study. All patients were subjected to the Mental State Score (MSS) test, and venous blood ammonia was measured on the same day of VEP recording. In 10/14 (71%) patients some VEP recording abnormality was detected. In the cirrhotic patients, P100 latency was significantly longer (P < 0.05) than in controls. Low amplitude was observed in 8 patients compared to controls. Marked increase of N75 (3 patients) and marked increase of N145 (2 patients) were observed. Mean blood ammonia and MSS score were normal in all patients. No correlation was found between both MSS score and blood ammonia levels and the P100 delay. Five out of 10 patients with pathologic VEP developed hepatic encephalpathy during a follow-up of one year, compared to one out of 4 patients with no pathology on VEP recording. VEP recording may be a valuable tool in assessing patients with early hepatic encephalopathy and in predicting encephalopathy. PMID:12533959

  2. Liver transplant for intentional acetaminophen overdose and hepatic encephalopathy: a conflict between beneficence and justice.

    PubMed

    Willey, Joshua Z; Tolchin, Benjamin David

    2014-06-01

    In cases of severe acetaminophen-induced acute liver failure and hepatic encephalopathy, liver transplant can be the only real hope for neurologic recovery and indeed survival. In such cases, the bioethical principles of beneficence and justice often come into conflict. This article examines a case in which a neurologist managing an acetaminophen-overdose patient in the neurologic intensive care unit is faced with a conflict between her patient's need for a liver transplant and the needs of other patients on the transplant list.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

    Kunutsor, Setor K

    2015-12-01

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

  5. Comparison of Transmissible Mink Encephalopathy Isolates in Raccoons

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Owing to its susceptibility to various transmissible spongiform encephalopathies (TSE) and relatively short incubation times, the raccoon (Procyon lotor) has been suggested as a model for TSE strain differentiation. Transmissible mink encephalopathy (TME) is a prion disease of undetermined origin in...

  6. Evaluation of the zoonotic potential of transmissible mink encephalopathy

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  7. Typical and atypical cases of bovine spongiform encephalopathy

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bovine spongiform encephalopathy (BSE) is a transmissible spongiform encephalopathy of cattle, first detected in 1986 in the United Kingdom and subsequently in other countries. It is the most likely cause of variant Creutzfeldt-Jakob disease (vCJD) in humans, but the origin of BSE has not been eluci...

  8. The Spectrum of Disease in Chronic Traumatic Encephalopathy

    ERIC Educational Resources Information Center

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

    2013-01-01

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

  9. Modeling Chronic Traumatic Encephalopathy: The Way Forward for Future Discovery

    PubMed Central

    Turner, Ryan C.; Lucke-Wold, Brandon P.; Logsdon, Aric F.; Robson, Matthew J.; Lee, John M.; Bailes, Julian E.; Dashnaw, Matthew L.; Huber, Jason D.; Petraglia, Anthony L.; Rosen, Charles L.

    2015-01-01

    Despite the extensive media coverage associated with the diagnosis of chronic traumatic encephalopathy (CTE), our fundamental understanding of the disease pathophysiology remains in its infancy. Only recently have scientific laboratories and personnel begun to explore CTE pathophysiology through the use of preclinical models of neurotrauma. Some studies have shown the ability to recapitulate some aspects of CTE in rodent models, through the use of various neuropathological, biochemical, and/or behavioral assays. Many questions related to CTE development, however, remain unanswered. These include the role of impact severity, the time interval between impacts, the age at which impacts occur, and the total number of impacts sustained. Other important variables such as the location of impacts, character of impacts, and effect of environment/lifestyle and genetics also warrant further study. In this work, we attempt to address some of these questions by exploring work previously completed using single- and repetitive-injury paradigms. Despite some models producing some deficits similar to CTE symptoms, it is clear that further studies are required to understand the development of neuropathological and neurobehavioral features consistent with CTE-like features in rodents. Specifically, acute and chronic studies are needed that characterize the development of tau-based pathology. PMID:26579067

  10. Modeling Chronic Traumatic Encephalopathy: The Way Forward for Future Discovery.

    PubMed

    Turner, Ryan C; Lucke-Wold, Brandon P; Logsdon, Aric F; Robson, Matthew J; Lee, John M; Bailes, Julian E; Dashnaw, Matthew L; Huber, Jason D; Petraglia, Anthony L; Rosen, Charles L

    2015-01-01

    Despite the extensive media coverage associated with the diagnosis of chronic traumatic encephalopathy (CTE), our fundamental understanding of the disease pathophysiology remains in its infancy. Only recently have scientific laboratories and personnel begun to explore CTE pathophysiology through the use of preclinical models of neurotrauma. Some studies have shown the ability to recapitulate some aspects of CTE in rodent models, through the use of various neuropathological, biochemical, and/or behavioral assays. Many questions related to CTE development, however, remain unanswered. These include the role of impact severity, the time interval between impacts, the age at which impacts occur, and the total number of impacts sustained. Other important variables such as the location of impacts, character of impacts, and effect of environment/lifestyle and genetics also warrant further study. In this work, we attempt to address some of these questions by exploring work previously completed using single- and repetitive-injury paradigms. Despite some models producing some deficits similar to CTE symptoms, it is clear that further studies are required to understand the development of neuropathological and neurobehavioral features consistent with CTE-like features in rodents. Specifically, acute and chronic studies are needed that characterize the development of tau-based pathology. PMID:26579067

  11. Imaging in sepsis-associated encephalopathy--insights and opportunities.

    PubMed

    Stubbs, Daniel J; Yamamoto, Adam K; Menon, David K

    2013-10-01

    Sepsis-associated encephalopathy (SAE) refers to a clinical spectrum of acute neurological dysfunction that arises in the context of sepsis. Although the pathophysiology of SAE is incompletely understood, it is thought to involve endothelial activation, blood-brain barrier leakage, inflammatory cell migration, and neuronal loss with neurotransmitter imbalance. SAE is associated with a high risk of mortality. Imaging studies using MRI and CT have demonstrated changes in the brains of patients with SAE that are also seen in disorders such as stroke. Next-generation imaging techniques such as magnetic resonance spectroscopy, diffusion tensor imaging and PET, as well as experimental imaging modalities, provide options for early identification of patients with SAE, and could aid in identification of pathophysiological processes that represent possible therapeutic targets. In this Review, we explore the recent literature on imaging in SAE, relating the findings of these studies to pathological data and experimental studies to obtain insights into the pathophysiology of sepsis-associated neurological dysfunction. Furthermore, we suggest how novel imaging technologies can be used for early-stage proof-of-concept and proof-of-mechanism translational studies, which may help to improve diagnosis in SAE.

  12. Hemophagocytic lymphohistiocytosis: A rare cause of recurrent encephalopathy

    PubMed Central

    Sulaiman, Raashda Ainuddin; Shaheen, Marwan Yassin; Al-Zaidan, Hamad; Al-Hassnan, Zuhair; Al-Sayed, Moeenaldeen; Rahbeeni, Zuhair; Bakshi, Nasir Ahmed; Kaya, Namik; Aldosary, Mazhor; Al-Owain, Mohammed

    2016-01-01

    Summary We report an unusual case of recurrent encephalopathy due to acquired hemophagocytic lymphohistiocytosis (HLH) in a patient with propionic acidemia (PA). PA is an inherited metabolic disorder in which patients often present with encephalopathy and pancytopenia during metabolic decompensation. However, these patients may rarely develop HLH with similar presentation. This case illustrates the need to distinguish HLH induced encephalopathy from the one secondary to metabolic decompensation in these patients, as early diagnosis and treatment of HLH improves prognosis. This case also highlights the importance of considering HLH in patients presenting with unexplained encephalopathy, as early diagnosis and treatment is lifesaving in this otherwise lethal condition. To our knowledge this is the first case report of acquired HLH presenting as recurrent encephalopathy followed by complete recovery, in a metabolically stable patient with PA.

  13. Hemophagocytic lymphohistiocytosis: A rare cause of recurrent encephalopathy.

    PubMed

    Sulaiman, Raashda Ainuddin; Shaheen, Marwan Yassin; Al-Zaidan, Hamad; Al-Hassnan, Zuhair; Al-Sayed, Moeenaldeen; Rahbeeni, Zuhair; Bakshi, Nasir Ahmed; Kaya, Namik; Aldosary, Mazhor; Al-Owain, Mohammed

    2016-08-01

    We report an unusual case of recurrent encephalopathy due to acquired hemophagocytic lymphohistiocytosis (HLH) in a patient with propionic acidemia (PA). PA is an inherited metabolic disorder in which patients often present with encephalopathy and pancytopenia during metabolic decompensation. However, these patients may rarely develop HLH with similar presentation. This case illustrates the need to distinguish HLH induced encephalopathy from the one secondary to metabolic decompensation in these patients, as early diagnosis and treatment of HLH improves prognosis. This case also highlights the importance of considering HLH in patients presenting with unexplained encephalopathy, as early diagnosis and treatment is lifesaving in this otherwise lethal condition. To our knowledge this is the first case report of acquired HLH presenting as recurrent encephalopathy followed by complete recovery, in a metabolically stable patient with PA. PMID:27672548

  14. Hemophagocytic lymphohistiocytosis: A rare cause of recurrent encephalopathy.

    PubMed

    Sulaiman, Raashda Ainuddin; Shaheen, Marwan Yassin; Al-Zaidan, Hamad; Al-Hassnan, Zuhair; Al-Sayed, Moeenaldeen; Rahbeeni, Zuhair; Bakshi, Nasir Ahmed; Kaya, Namik; Aldosary, Mazhor; Al-Owain, Mohammed

    2016-08-01

    We report an unusual case of recurrent encephalopathy due to acquired hemophagocytic lymphohistiocytosis (HLH) in a patient with propionic acidemia (PA). PA is an inherited metabolic disorder in which patients often present with encephalopathy and pancytopenia during metabolic decompensation. However, these patients may rarely develop HLH with similar presentation. This case illustrates the need to distinguish HLH induced encephalopathy from the one secondary to metabolic decompensation in these patients, as early diagnosis and treatment of HLH improves prognosis. This case also highlights the importance of considering HLH in patients presenting with unexplained encephalopathy, as early diagnosis and treatment is lifesaving in this otherwise lethal condition. To our knowledge this is the first case report of acquired HLH presenting as recurrent encephalopathy followed by complete recovery, in a metabolically stable patient with PA.

  15. Hemophagocytic lymphohistiocytosis: A rare cause of recurrent encephalopathy

    PubMed Central

    Sulaiman, Raashda Ainuddin; Shaheen, Marwan Yassin; Al-Zaidan, Hamad; Al-Hassnan, Zuhair; Al-Sayed, Moeenaldeen; Rahbeeni, Zuhair; Bakshi, Nasir Ahmed; Kaya, Namik; Aldosary, Mazhor; Al-Owain, Mohammed

    2016-01-01

    Summary We report an unusual case of recurrent encephalopathy due to acquired hemophagocytic lymphohistiocytosis (HLH) in a patient with propionic acidemia (PA). PA is an inherited metabolic disorder in which patients often present with encephalopathy and pancytopenia during metabolic decompensation. However, these patients may rarely develop HLH with similar presentation. This case illustrates the need to distinguish HLH induced encephalopathy from the one secondary to metabolic decompensation in these patients, as early diagnosis and treatment of HLH improves prognosis. This case also highlights the importance of considering HLH in patients presenting with unexplained encephalopathy, as early diagnosis and treatment is lifesaving in this otherwise lethal condition. To our knowledge this is the first case report of acquired HLH presenting as recurrent encephalopathy followed by complete recovery, in a metabolically stable patient with PA. PMID:27672548

  16. The Expanding Clinical Spectrum of Genetic Pediatric Epileptic Encephalopathies.

    PubMed

    Shbarou, Rolla; Mikati, Mohamad A

    2016-05-01

    Pediatric epileptic encephalopathies represent a clinically challenging and often devastating group of disorders that affect children at different stages of infancy and childhood. With the advances in genetic testing and neuroimaging, the etiologies of these epileptic syndromes are now better defined. The various encephalopathies that are reviewed in this article include the following: early infantile epileptic encephalopathy or Ohtahara syndrome, early myoclonic encephalopathy, epilepsy of infancy with migrating focal seizures, West syndrome, severe myoclonic epilepsy in infancy (Dravet syndrome), Landau-Kleffner syndrome, Lennox-Gastaut syndrome, and epileptic encephalopathy with continuous spike-and-wave during sleep. Their clinical features, prognosis as well as underlying genetic etiologies are presented and updated. PMID:27544470

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

    PubMed

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

    2016-01-01

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

  18. Chronic Traumatic Encephalopathy and Movement Disorders: Update.

    PubMed

    Tarazi, Apameh; Tator, Charles H; Tartaglia, Maria Carmela

    2016-05-01

    Association of repetitive brain trauma with progressive neurological deterioration has been described since the 1920s. Punch drunk syndrome and dementia pugilistica (DP) were introduced first to explain symptoms in boxers, and more recently, chronic traumatic encephalopathy (CTE) has been used to describe a neurodegenerative disease in athletes and military personal with a history of multiple concussions. Although there are many similarities between DP and CTE, a number of key differences are apparent especially when comparing movement impairments. The aim of this review is to compare clinical and pathological aspects of DP and CTE with a focus on disorders of movement. PMID:27021775

  19. Repetitive Head Impacts and Chronic Traumatic Encephalopathy.

    PubMed

    McKee, Ann C; Alosco, Michael L; Huber, Bertrand R

    2016-10-01

    Chronic traumatic encephalopathy (CTE) is a distinctive neurodegenerative disease that occurs as a result of repetitive head impacts. CTE can only be diagnosed by postmortem neuropathologic examination of brain tissue. CTE is a unique disorder with a pathognomonic lesion that can be reliably distinguished from other neurodegenerative diseases. CTE is associated with violent behaviors, explosivity, loss of control, depression, suicide, memory loss and cognitive changes. There is increasing evidence that CTE affects amateur athletes as well as professional athletes and military veterans. CTE has become a major public health concern.

  20. Repetitive Head Impacts and Chronic Traumatic Encephalopathy.

    PubMed

    McKee, Ann C; Alosco, Michael L; Huber, Bertrand R

    2016-10-01

    Chronic traumatic encephalopathy (CTE) is a distinctive neurodegenerative disease that occurs as a result of repetitive head impacts. CTE can only be diagnosed by postmortem neuropathologic examination of brain tissue. CTE is a unique disorder with a pathognomonic lesion that can be reliably distinguished from other neurodegenerative diseases. CTE is associated with violent behaviors, explosivity, loss of control, depression, suicide, memory loss and cognitive changes. There is increasing evidence that CTE affects amateur athletes as well as professional athletes and military veterans. CTE has become a major public health concern. PMID:27637402

  1. Fourier Transform Infrared Spectroscopy Demonstrates The Reactivity Of The Protonated Carboxyl Group Of The Acid Salt Of Calcium Bilirubinate.

    NASA Astrophysics Data System (ADS)

    Soloway, R. D.; Wu, J.-G.; Xu, D.-F.; Zhang, Y.-F.; Martini, D. K.; Hong, N.-K.; Crowther, R. S.

    1989-12-01

    Calcium bilirubinate is a major salt in pigment gallstones. Bilirubin IX (H2BR) is a tetrapyrrole with 1 propionic acid side chain on both the B and C rings. A striking feature is the strong intramolecular hydrogen bonding of both carboxyl groups as determined by x-ray diffraction. This greatly reduces aqueous solubility. Much less is known about the structure of the salts of calcium bilirubinate since single crystals have not been formed. One or both carboxyl groups of bilirubin may coordinate with calcium in stone, forming the acid or neutral salt.

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

    PubMed Central

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

    2015-01-01

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

  3. Inaccuracies in measurement of conjugated and unconjugated bilirubin in bile with ethyl anthranilate diazo and solvent-partition methods.

    PubMed Central

    Ostrow, J D; Boonyapisit, S T

    1978-01-01

    A criticial evaluation was made of the ethyl anthranilate diazo and two solvent-partition methods for the determination of conjugated and unconjugated bilirubin in human and rat bile. The ethyl anthranilate diazo reagent, which reacts only with conjugated bilirubin in serum, also diazotized a variable proportion of unconjugated bilirubin in bile and thus overestimated the concentration of monoconjugates. With the Weber-Schalm and modified Folsch solvent-partition methods applied to human or rat bile, 4--9% of added 14C-labelled unconjugated bilirubin partitioned with the conjugated bilirubin in the upper phase, and 4--9% of added 14C-labelled conjugated bilirubin partitioned into the lower phase. With dog bile, the spill-over of 14C-labelled bilirubin into the lower phase was 9--11%. Analysis of azopigments from the Weber-Schalm partition confirmed that over two-thirds of the bilirubin in the lower phase represents monoconjugates, principally the less-polar monoxylosides and monoglucosides. These solvent-partition methods thus overestimate the concentration of unconjugated bilirubin in bile. PMID:687371

  4. Adeno-associated virus vector serotypes mediate sustained correction of bilirubin UDP glucuronosyltransferase deficiency in rats.

    PubMed

    Seppen, Jurgen; Bakker, Conny; de Jong, Berry; Kunne, Cindy; van den Oever, Karin; Vandenberghe, Kristin; de Waart, Rudi; Twisk, Jaap; Bosma, Piter

    2006-06-01

    Crigler-Najjar (CN) patients have no bilirubin UDP glucuronosyltransferase (UGT1A1) activity and suffer brain damage because of bilirubin toxicity. Vectors based on adeno-associated virus (AAV) serotype 2 transduce liver cells with relatively low efficiency. Recently, AAV serotypes 1, 6, and 8 have been shown to be more efficient for liver cell transduction. We compared AAV serotypes 1, 2, 6, and 8 for correction of UGT1A1 deficiency in the Gunn rat model of CN disease. Adult Gunn rats were injected with CMV-UGT1A1 AAV vectors. Serum bilirubin was decreased over the first year by 64% for AAV1, 16% for AAV2, 25% for AAV6, and 35% for AAV8. Antibodies to UGT1A1 were detected after injection of all AAV serotypes. An AAV1 UGT1A1 vector with the liver-specific albumin promoter corrected serum bilirubin levels but did not induce UGT1A1 antibodies. Two years after injection of AAV vectors all animals had large lipid deposits in the liver. These lipid deposits were not seen in age-matched control animals. AAV1 vectors are promising candidates for CN gene therapy because they can mediate a reduction in serum bilirubin levels in Gunn rats that would be therapeutic in humans. PMID:16581301

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

    PubMed Central

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

    2014-01-01

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

  6. Atypical presentation of human bocavirus: Severe respiratory tract infection complicated with encephalopathy.

    PubMed

    Akturk, Hacer; Sık, Guntulu; Salman, Nuran; Sutcu, Murat; Tatli, Burak; Ciblak, Meral Akcay; Erol, Oguz Bulent; Torun, Selda Hancerli; Citak, Agop; Somer, Ayper

    2015-11-01

    Human bocavirus (HBOV) has been reported as a worldwide distributed respiratory pathogen. It has also been associated with encephalitis recently by detection of the virus in cerebrospinal fluid (CSF) of patients presented with encephalitis. This retrospective study aimed to present clinical features of HBOV infections in children with respiratory symptoms and describe unexplained encephalopathy in a subgroup of these patients. Results of 1,143 pediatric nasal samples from mid-December 2013 to July 2014 were reviewed for detection of HBOV. A multiplex real time polymerase chain reaction assay was used for viral detection. Medical records of the patients were retrospectively analyzed. HBOV was detected in 30 patients (2.6%). Median age was 14 months (5-80). Clinical diagnoses were upper respiratory tract infection (n = 10), bronchopneumonia (n = 9), acute bronchiolitis (n = 5), pneumonia (n = 4), acute bronchitis (n = 1), and asthma execarbation (n = 1). Hospitalization was required in 16 (53.3%) patients and 10 (62.5%) of them admitted to pediatric intensive care unit (PICU). Noninvasive mechanical ventilation modalities was applied to four patients and mechanical ventilation to four patients. Intractable seizures developed in four patients while mechanically ventilated on the 2nd-3rd days of PICU admission. No specific reason for encephalopathy was found after a thorough investigation. No mortality was observed, but two patients were discharged with neurological sequela. HBOV may lead to respiratory infections in a wide spectrum of severity. This report indicates its potential to cause severe respiratory infections requiring PICU admission and highlights possible clinical association of HBOV and encephalopathy, which developed during severe respiratory infection. PMID:25966820

  7. Three-dimensional brain metabolic imaging in patients with toxic encephalopathy

    SciTech Connect

    Callender, T.J.; Duhon, D.; Ristovv, M. ); Morrow, L. ); Subramanian, K. )

    1993-02-01

    Thirty-three workers, ages 24 to 63, developed clinical toxic encephalopathy after exposure to neurotoxins and were studied by SPECT brain scans. Five were exposed to pesticides, 13 were acutely exposed to mixtures of solvents, 8 were chronically exposed to mixtures of hazardous wastes that contained organic solvents, 2 were acutely exposed to phosgene and other toxins, and 5 had exposures to hydrogen sulfide. Twenty-nine had neuropsychological testing and all had a medical history and physical. Of the workers who had a clinical diagnosis of toxic encephalopathy, 31 (93.9%) had abnormal SPECT brain scans with the most frequent areas of abnormality being temporal lobes (67.7%), frontal lobes (61.3%), basal ganglia (45.2%), thalamus (29.0%), parietal lobes (12.9%), motorstrip (9.68%), cerebral hemisphere (6.45%), occipital lobes (3.23%), and caudate nucleus (3.23%). Twenty-three out of 29 (79.3%) neuropsychological evaluations were abnormal. Other modalities when performed included the following percentages of abnormals: NCV, 33.3%; CPT sensory nerve testing, 91.3%, vestibular function testing, 71.4%; olfactory testing, 89.2%; sleep EEG analysis, 85.7%; EEG, 8.33%; CT, 7.14%; and MRI brain scans, 28.6%. The complex of symptoms seen in toxic encephalopathy implies dysfunction involving several CNS regions. This series of patients adds to the previous experience of brain metabolic imaging and demonstrates that certain areas of the brain are typically affected despite differences in toxin structure, that these lesions can be globally defined by SPECT/PET brain scans, that these lesions correlate well with clinical and neuropsychological testing, and that such testing is a useful adjunct to previous methods. EEG and structural brain imaging such as CT and MRI are observed to have poor sensitivity in this type of patient. 32 refs., 5 tabs.

  8. Posterior reversible encephalopathy syndrome secondary to blood transfusion.

    PubMed

    Singh, Karanbir; Gupta, Rajesh; Kamal, Haris; Silvestri, Nicholas J; Wolfe, Gil I

    2015-03-01

    The appearance of posterior reversible encephalopathy syndrome (PRES) after blood transfusion is rare and has only been reported in three patients to our knowledge. We report a fourth patient with PRES secondary to blood transfusion. A 36-year-old woman with a history of menorrhagia presented to the emergency department with severe fatigue. She had a hemoglobin of 1.7 g/dl and received four units of red blood cells over 15 hours. On day 6 post-transfusion she returned with confusion, headache and a generalized tonic-clonic seizure. The MRI of her brain was consistent with PRES. The following day her confusion worsened, repeat MRI of the brain showed new T2-weighted lesions. Over next 10 days her mental status gradually improved close to her baseline. A repeat MRI of the brain showed resolution of the T2-weighted lesions. The clinical presentation, radiological findings and disease progression in our patient was consistent with PRES. Other than the blood transfusions, there were no apparent risk factors for PRES. The prior three patients with post-transfusion PRES have been reported in middle-aged women with uterine fibroids. It is suspected that these patients have a subacute to chronic anemic state due to ongoing menorrhagia. It is interesting to note that no cases of PRES post-transfusion have been reported in the setting of acute blood loss, such as from trauma. It is postulated that an abrupt increase in hemoglobin causes a rapid rise in blood viscosity and loss of hypoxic vasodilation. Subsequent endothelial damage and brain capillary leakage results in PRES. This constellation of changes may not occur after transfusion in patients with more acute blood loss.

  9. A neurologist's approach to delirium: diagnosis and management of toxic metabolic encephalopathies.

    PubMed

    Krishnan, Vaishnav; Leung, Lester Y; Caplan, Louis R

    2014-02-01

    Toxic metabolic encephalopathies (TMEs) present as an acute derangement in consciousness, cognition and behavior, and can be brought about by various triggers, including endocrine and metabolic disturbances, exogenous toxins, pain and infection. Also referred to as "delirium" or "acute confusional states," TMEs are characterized by (1) an altered level of consciousness and activity, (2) global changes in cognition with inattention, (3) a fluctuating course with disturbances in the sleep-wake cycle, and (4) asterixis and myoclonus. The pathophysiology of this syndrome is poorly understood. Imbalanced neurotransmitter signaling and pathologically heightened brain inflammatory cytokine signaling have been proposed as candidate mechanisms. Focal brain lesions can also occasionally mimic TMEs. A neurological examination is required to identify the presence of focal findings, which when present, identify a new focal lesion or the recrudescence of prior ischemic, inflammatory or neoplastic insults. Diagnostic testing must include a search for metabolic and infectious derangements. Offending medications should be withdrawn. Magnetic resonance imaging, cerebrospinal fluid analysis and electroencephalography should be considered in select clinical situations. In addition to being an unpleasant experience for the patient and family, this condition is associated with extended hospital stays, increased mortality and high costs. In individuals with diminished cognitive reserve, episodes of TME lead to an accelerated decline in cognitive functioning. Starting with an illustrative case, this paper provides a neurologist's approach to the diagnosis, differential diagnosis and management of toxic metabolic encephalopathies.

  10. Unconjugated bilirubin and the bile from light exposed Gunn rats inhibit intestinal water and electrolyte absorption.

    PubMed Central

    Guandalini, S; Fasano, A; Albini, F; Marchesano, G; Nocerino, A; De Curtis, M; Rubaltelli, F F; Pettenazzo, A; Rubino, A

    1988-01-01

    Jaundiced babies undergoing phototherapy often develop diarrhoea. The cause of it is still uncertain. Increasing evidence supports a role of a secretory mechanism for the diarrhoea. We therefore studied the effects of bile from congenitally jaundiced rats undergoing phototherapy and of unconjugated bilirubin on rat small intestine in vivo and in vitro. Results suggest that: (1) the bile from homozygous Gunn rats under phototherapy has an anti-absorptive effect when tested in the perfused jejunum of normal Wistar rats; (2) unconjugated bilirubin has a dose dependent secretory effect on the intestinal transport of water and electrolytes, when tested in the same system. Alteration of cyclic AMP or cyclic GMP, known intracellular mediators of secretion, was not observed. We conclude that free bilirubin is an intestinal secretagogue acting by an as yet unknown mechanism, that may mediate the secretory type of diarrhoea in jaundiced neonates undergoing phototherapy. PMID:3356369

  11. Diazo-based assay for total bilirubin in a coated thin film evaluated.

    PubMed

    Weiss, J S; Sundberg, M W; Dappen, G M; Spayd, R W; Wu, T W; Jatlow, P; Seligson, D

    1984-08-01

    We compared results for total bilirubin as measured on a coated thin film and by the Evelyn-Malloy and Jendrassik-Gróf methods. We examined serum samples from patients and studied the effects of protein, hemoglobin, and lipids on bilirubin measurement. Results from the thin-film assay compared favorably with those of the other methods. Total and within-day precision (CV), assessed over a one-year period, were better than 6% and 3%, respectively, at all concentrations. Analytical recovery was 99 +/- 3%. Samples from individuals having a wide range of liver diseases demonstrated, by linear regression, good correlation between the thin-film method and the two wet-chemistry methods (correlation coefficients of 0.990 and 0.994). We conclude that the thin-film method offers a valid alternative assay for total bilirubin. PMID:6744577

  12. Management options for minimal hepatic encephalopathy.

    PubMed

    Bajaj, Jasmohan S

    2008-12-01

    Minimal hepatic encephalopathy (MHE) is a neurocognitive dysfunction that is present in the majority of patients with cirrhosis. MHE has a characteristic cognitive profile that cannot be diagnosed clinically. This cognitive dysfunction is independent of sleep dysfunction or problems with overall intelligence. MHE has a significant impact on quality of life, the ability to function in daily life and progression to overt hepatic encephalopathy. Driving ability can be impaired in MHE and this may be a significant factor behind motor vehicle accidents. A crucial aspect of the clinical care of MHE patients is their driving history, which is often ignored during routine care and can add a vital dimension to the overall disease assessment. Driving history should be an integral part of the care of patients with MHE. The preserved communication skills and lack of specific signs and insight make MHE difficult to diagnose. The predominant strategies for MHE diagnosis are psychometric or neurophysiological testing. These are usually limited by financial, normative or time constraints. Studies into inhibitory control, cognitive drug research and critical flicker frequency tests are encouraging. These tests do not require a psychologist for administration and interpretation. Lactulose and probiotics have been studied for their potential use as therapies for MHE, but these are not standard-of-care practices at this time. Therapy can improve the quality of life in MHE patients but the natural history, specific diagnostic strategies and treatment options are still being investigated. PMID:19090738

  13. Clinical presentation of chronic traumatic encephalopathy

    PubMed Central

    Daneshvar, Daniel H.; Baugh, Christine M.; Seichepine, Daniel R.; Montenigro, Philip H.; Riley, David O.; Fritts, Nathan G.; Stamm, Julie M.; Robbins, Clifford A.; McHale, Lisa; Simkin, Irene; Stein, Thor D.; Alvarez, Victor E.; Goldstein, Lee E.; Budson, Andrew E.; Kowall, Neil W.; Nowinski, Christopher J.; Cantu, Robert C.; McKee, Ann C.

    2013-01-01

    Objective: The goal of this study was to examine the clinical presentation of chronic traumatic encephalopathy (CTE) in neuropathologically confirmed cases. Methods: Thirty-six adult male subjects were selected from all cases of neuropathologically confirmed CTE at the Boston University Center for the Study of Traumatic Encephalopathy brain bank. Subjects were all athletes, had no comorbid neurodegenerative or motor neuron disease, and had next-of-kin informants to provide retrospective reports of the subjects' histories and clinical presentations. These interviews were conducted blind to the subjects' neuropathologic findings. Results: A triad of cognitive, behavioral, and mood impairments was common overall, with cognitive deficits reported for almost all subjects. Three subjects were asymptomatic at the time of death. Consistent with earlier case reports of boxers, 2 relatively distinct clinical presentations emerged, with one group whose initial features developed at a younger age and involved behavioral and/or mood disturbance (n = 22), and another group whose initial presentation developed at an older age and involved cognitive impairment (n = 11). Conclusions: This suggests there are 2 major clinical presentations of CTE, one a behavior/mood variant and the other a cognitive variant. PMID:23966253

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

    NASA Astrophysics Data System (ADS)

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

    2008-05-01

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

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

    PubMed

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

    2015-04-01

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

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

    PubMed Central

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

    1975-01-01

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

  17. A Case of Chronic Wernicke’s Encephalopathy: A Neuropsychological Study

    PubMed Central

    Oudman, Erik; Van der Stigchel, Stefan; Postma, Albert; Wijnia, Jan W.; Nijboer, Tanja C. W.

    2014-01-01

    A 54-year-old woman was referred to our Korsakoff Center because of extensive cognitive problems following acute Wernicke’s encephalopathy (WE). She had a relatively short history of alcohol abuse and was found lying on the floor in her home by her son. After 5 days without treatment, she was diagnosed with WE in a general hospital. During the course of the disease, minimal change to the acute situation occurred, with chronic confusion, attention deficits, and incoherent behavior symptoms most notable unlike classical Korsakoff’s syndrome. Neuropsychological assessment after 4 and 16 months after admission to the hospital revealed global cognitive decline, with striking impairments in attentional, executive, and memory functions. The present case study suggests that the state of confusion and the neuropsychological symptoms in WE can become chronic in case of very late treatment. We therefore recommend that confused alcoholics should receive appropriate parenteral thiamine according to the current clinical standards. PMID:24904442

  18. Efficacy of liver assisting in patients with hepatic encephalopathy with special focus on plasma exchange.

    PubMed

    Stenbøg, Poul; Busk, Troels; Larsen, Fin Stolze

    2013-06-01

    Severe liver injury result in development of hepatic encephalopathy (HE) and often also in brain edema that is a potentially fatal complication. HE and brain edema are correlated to the level and persistence of hyperammonemia and the presence of systemic inflammation. Treatment of HE and brain edema is based on restoring and keeping normal physiological variables including tonicity, blood gasses, lactate, temperature and vascular resistance by a wide variety of interventions. In addition liver support devices improve the stage of HE, cerebral metabolic rate for oxygen and glucose, and are used either as a bridge to liver transplantation or liver recovery in patients with fulminant hepatic failure and in patients with acute-on-chronic liver failure. This short review will mainly focus on the management and efficacy of doing plasma exchange on HE in patients with acute HE. PMID:23572273

  19. Calcium bilirubinate intercalated calcite single crystal: evidence for microstructure of pigment gallstones

    NASA Astrophysics Data System (ADS)

    Liu, H. Z.; Xu, D. J.; Soloway, Roger D.; Zhang, Y. Z.; Xu, Duan-Fu; Wu, JinGuang

    1994-01-01

    During the preparation of calcium bilirubinate (CaBR) single crystals, brown crystals were grown in a gel solution of CaCl2/Sodium bilirubinate. X-ray diffraction analysis proved that the crystal was calcite. FTIR investigations support this result. However, the subtracted spectra revealed that the CaBR dispersed in the crystals and interacted with calcite on the molecular level, since the maximum band shift of the CaBR in calcite from the correspond bands of CaBR was ca. 20 cm-1. It was confirmed that microstructure also by x- ray diffraction and photoacoustic Fourier transform infrared spectroscopy.

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

    PubMed

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

    2013-12-01

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

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

    PubMed

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

    2016-09-01

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

  2. Acute Pancreatitis, Hepatitis and Bone Erosion in Acute Yellow Phosphorous Compound Poisoning – A Rare Complication

    PubMed Central

    Kamarthi, Prabhakar; Gopu, Arun Vardharaju; Prasad, Reddy; Srinivasa, Chandrakala

    2016-01-01

    We report a case of acute pancreatitis and hepatitis following ingestion of yellow phosphorous. The condition of the patient progressed to encephalopathy and bony erosion of the nasal septum. Fungal mass was observed in both the nasal cavities by endoscopy. Microbiological investigation revealed the identity of the fungus as Aspergillus flavus and Candida tropicalis. Patient improved with fluconazole treatment. PMID:27504287

  3. Acute Pancreatitis, Hepatitis and Bone Erosion in Acute Yellow Phosphorous Compound Poisoning - A Rare Complication.

    PubMed

    Kamarthi, Prabhakar; Subramani, Parimala; Gopu, Arun Vardharaju; Prasad, Reddy; Srinivasa, Chandrakala

    2016-06-01

    We report a case of acute pancreatitis and hepatitis following ingestion of yellow phosphorous. The condition of the patient progressed to encephalopathy and bony erosion of the nasal septum. Fungal mass was observed in both the nasal cavities by endoscopy. Microbiological investigation revealed the identity of the fungus as Aspergillus flavus and Candida tropicalis. Patient improved with fluconazole treatment. PMID:27504287

  4. Hepatic Encephalopathy-the Old and the New.

    PubMed

    Kandiah, Prem A; Kumar, Gagan

    2016-07-01

    Hepatic encephalopathy occurs ubiquitously in all causes of advanced liver failure, however, its implications on mortality diverge and vary depending upon acuity and severity of liver failure. This associated mortality has decreased in subsets of liver failure over the last 20 years. Aside from liver transplantation, this improvement is not attributable to a single intervention but likely to a combination of practical advances in critical care management. Misconceptions surrounding many facets of hepatic encephalopathy exists due to heterogeneity in presentation, pathophysiology and outcome. This review is intended to highlight the important concepts, rationales and strategies for managing hepatic encephalopathy.

  5. Severe early onset ethylmalonic encephalopathy with West syndrome.

    PubMed

    Papetti, Laura; Garone, Giacomo; Schettini, Livia; Giordano, Carla; Nicita, Francesco; Papoff, Paola; Zeviani, Massimo; Leuzzi, Vincenzo; Spalice, Alberto

    2015-12-01

    Ethylmalonic encephalopathy (EE) is a rare autosomal recessive disorder characterized by early onset encephalopathy, chronic diarrhoea, petechiae, orthostatic acrocyanosis and defective cytochrome c oxidase (COX) in muscle and brain. High levels of lactic, ethylmalonic and methylsuccinic acids are detected in body fluids. EE is caused by mutations in ETHE1 gene, a mitochondrial sulfur dioxygenase. Neurologic signs and symptoms include progressively delayed development, hypotonia, seizures, and abnormal movements. We report on the clinical, electroencephalographic and MRI findings of a baby with a severe early onset encephalopathy associated with novel ETHE1 gene mutation. This is the first case described in literature with an early pure epileptic onset, presenting with West syndrome.

  6. Legal Responsibilities of Physicians When They Diagnose Hepatic Encephalopathy.

    PubMed

    Vierling, John M

    2015-08-01

    Both covert hepatic encephalopathy (CHE) and overt hepatic encephalopathy (OHE) impair the ability to operate machinery. The legal responsibilities of US physicians who diagnose and treat patients with hepatic encephalopathy vary among states. It is imperative that physicians know the laws regarding reporting in their state. OHE represents a neuropsychiatric impairment that meets general reporting criteria. The medical advisory boards of the states have not identified OHE as a reportable condition. In the absence of validated diagnostic guidelines, physicians are not obligated to perform tests for CHE. There is a need for explicit guidance from professional associations regarding this issue.

  7. Spiroplasma spp. from transmissible spongiform encephalopathy brains or ticks induce spongiform encephalopathy in ruminants.

    PubMed

    Bastian, Frank O; Sanders, Dearl E; Forbes, Will A; Hagius, Sue D; Walker, Joel V; Henk, William G; Enright, Fred M; Elzer, Philip H

    2007-09-01

    Spiroplasma, small motile wall-less bacteria, are linked by molecular and serological studies to the transmissible spongiform encephalopathies (TSEs), which include scrapie in sheep, chronic wasting disease (CWD) in deer and Creutzfeldt-Jakob disease in humans. In this study, two experiments were undertaken to determine the role of spiroplasma in the pathogenesis of TSE. In experiment 1, Spiroplasma mirum, a rabbit tick isolate that had previously been shown to experimentally induce spongiform encephalopathy in rodents, was inoculated intracranially (IC) into ruminants. S. mirum-inoculated deer manifested clinical signs of TSE after 1.5 to 5.5 months incubation. The deer, as well as sheep and goats, inoculated with S. mirum developed spongiform encephalopathy in a dose-dependent manner. In experiment 2, spiroplasma closely related to S. mirum were isolated from TSE-affected brains via passage in embryonated eggs, and propagated in cell-free M1D media. Spiroplasma spp. isolates from scrapie-affected sheep brain and from CWD-affected deer brain inoculated IC into sheep and goats induced spongiform encephalopathy closely resembling natural TSE in these animals. These data show spiroplasma to be consistently associated with TSE, and able experimentally to cause TSE in ruminant animal models, therein questioning the validity of studies that have concluded the prion, a miss-folded protease-resistant protein that builds up in TSE brains during the course of the disease, to be the sole causal agent. The spiroplasma infection models reported here will be important for investigating factors involved in the pathogenesis of TSE since ruminants are the natural hosts.

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  10. Management of hepatic encephalopathy in the hospital.

    PubMed

    Leise, Michael D; Poterucha, John J; Kamath, Patrick S; Kim, W Ray

    2014-02-01

    Hepatic encephalopathy (HE) develops in up to 50% of patients with cirrhosis and is a feature of decompensated cirrhosis. With the goal of reviewing the evidence for treatment and prevention of overt hepatic encephalopathy, pubmed was searched using search terms hepatic encephalopathy AND treatment, limited to human studies from January 1, 2003, through December 1, 2013, and supplemented by key references. The inpatient incidence of HE is approximately 23,000 annually, and management of these patients is common for internists and subspecialists. Treatment of the hospitalized patient with HE has changed in recent years. Treatment entails 2 phases: induction and maintenance of remission. Most cases of significant HE are precipitated by infection, gastrointestinal bleeding, medications, or other culprits. All patients should be evaluated for secondary triggers of HE, and treatment should be initiated with a nonabsorbable disaccharide (ie, lactulose) in most patients. Rifaximin (off label) can be added in patients not responding to lactulose. Neomycin is a less preferred alternative to rifaximin owing to its adverse effect profile. Other therapies, including zinc, L-ornithine-L-aspartate, and branched-chain amino acids, can be considered for patients not responding to disaccharides and nonabsorbable antibiotics. Large portosystemic shunts may be embolized in patients with medically refractory recurrent or severe HE with otherwise well-compensated cirrhosis. Molecular Adsorbent Recirculating System is now available for patients with severe HE who do not respond to medical therapy. It is critically important that patients hospitalized with significant HE continue maintenance therapy at the time of dismissal to prevent further episodes. Patients with a first-time episode of HE can be administered lactulose, and careful instructions should be provided to patients and caregivers about dose titration to achieve 3 bowel movements daily. Patients with recurrent HE episodes

  11. Chronic Traumatic Encephalopathy: The Impact on Athletes.

    PubMed

    Galgano, Michael A; Cantu, Robert; Chin, Lawrence S

    2016-01-01

    Chronic traumatic encephalopathy (CTE) is a devastating neuropsychological condition afflicting a small percentage of athletes partaking in high-impact sports. The onset of symptoms lags years behind the inciting events. Repetitive minor head injuries are felt to be the main etiology behind CTE. Routine radiographic imaging generally is unremarkable in cases of CTE. Functional magnetic resonance imaging (fMRI), magnetic resonance spectroscopy (MRS), and diffusion tensor imaging (DTI) are advanced MRI-based sequences that have shown promise in detecting early radiographic findings that may be reflective of CTE. Progressive neuronal loss is the histopathological hallmark of this neurodegenerative disease. Strategizing earlier detection techniques is paramount in delivering optimal care to athletes afflicted with CTE. PMID:27088064

  12. Nonconvulsive status epilepticus disguising as hepatic encephalopathy.

    PubMed

    Jo, Yong Min; Lee, Sung Wook; Han, Sang Young; Baek, Yang Hyun; Ahn, Ji Hye; Choi, Won Jong; Lee, Ji Young; Kim, Sang Ho; Yoon, Byeol A

    2015-04-28

    Nonconvulsive status epilepticus has become an important issue in modern neurology and epileptology. This is based on difficulty in definitively elucidating the condition and its various clinical phenomena and on our inadequate insight into the intrinsic pathophysiological processes. Despite nonconvulsive status epilepticus being a situation that requires immediate treatment, this disorder may not be appreciated as the cause of mental status impairment. Although the pathophysiology of nonconvulsive status epilepticus remains unknown, this disorder is thought to lead to neuronal damage, so its identification and treatment are important. Nonconvulsive status epilepticus should be considered in the differential diagnosis of patients with liver cirrhosis presenting an altered mental status. We report a case of a 52-year-old male with liver cirrhosis presenting an altered mental status. He was initially diagnosed with hepatic encephalopathy but ultimately diagnosed with nonconvulsive status epilepticus by electroencephalogram.

  13. Does this patient have hypertensive encephalopathy?

    PubMed

    Christopoulou, Foteini; Rizos, Evangelos C; Kosta, Paraskevi; Argyropoulou, Maria I; Elisaf, Moses

    2016-05-01

    A 63-year-old man was admitted to our hospital for further investigation and management of brain metastases. The patient was initially presented with a 4-day history of confusion. On the day of admission, the patient was confused, agitated, disorientated in place and time, and had visual disturbances. His blood pressure was repeatedly recorded high, with levels of systolic blood pressure between 170-210 mm Hg. A brain magnetic resonance imaging showed areas of high signal on T2 and fluid-attenuated inversion recovery images, located bilaterally in the white matter of the occipital regions and unilateral in the left frontal lobe, suggestive of posterior reversible encephalopathy syndrome. Aggressive treatment of hypertension resulted in complete resolution of the clinical and radiologic features of the syndrome. PMID:26896240

  14. Neuroprotective Strategies after Neonatal Hypoxic Ischemic Encephalopathy

    PubMed Central

    Dixon, Brandon J.; Reis, Cesar; Ho, Wing Mann; Tang, Jiping; Zhang, John H.

    2015-01-01

    Neonatal hypoxic ischemic encephalopathy (HIE) is a devastating disease that primarily causes neuronal and white matter injury and is among the leading cause of death among infants. Currently there are no well-established treatments; thus, it is important to understand the pathophysiology of the disease and elucidate complications that are creating a gap between basic science and clinical translation. In the development of neuroprotective strategies and translation of experimental results in HIE, there are many limitations and challenges to master based on an appropriate study design, drug delivery properties, dosage, and use in neonates. We will identify understudied targets after HIE, as well as neuroprotective molecules that bring hope to future treatments such as melatonin, topiramate, xenon, interferon-beta, stem cell transplantation. This review will also discuss some of the most recent trials being conducted in the clinical setting and evaluate what directions are needed in the future. PMID:26389893

  15. Pathogenesis, Diagnosis, and Treatment of Hepatic Encephalopathy

    PubMed Central

    Atluri, Dileep K; Prakash, Ravi; Mullen, Kevin D

    2011-01-01

    Hepatic encephalopathy (HE) is a neuropsychiatric disorder seen in patients with advanced liver disease or porto-systemic shunts. Based on etiology and severity of HE, the World Congress of Gastroenterology has divided HE into categories and sub-categories. Many user-friendly computer-based neuropsychiatric tests are being validated for diagnosing covert HE. Currently, emphasis is being given to view HE deficits as a continuous spectrum rather than distinct stages. Ammonia is believed to play crucial role in pathogenesis of HE via astrocyte swelling and cerebral edema. However, evidence has been building up which supports the synergistic role of oxidative stress, inflammation and neurosteroids in pathogenesis of HE. At present, treatment of HE aims at decreasing the production and intestinal absorption of ammonia. But as the role of new pathogenetic mechanisms becomes clear, many potential new treatment strategies may become available for clinician. PMID:25755319

  16. Chronic traumatic encephalopathy and other neurodegenerative proteinopathies.

    PubMed

    Tartaglia, Maria Carmela; Hazrati, Lili-Naz; Davis, Karen D; Green, Robin E A; Wennberg, Richard; Mikulis, David; Ezerins, Leo J; Keightley, Michelle; Tator, Charles

    2014-01-01

    "Chronic traumatic encephalopathy" (CTE) is described as a slowly progressive neurodegenerative disease believed to result from multiple concussions. Traditionally, concussions were considered benign events and although most people recover fully, about 10% develop a post-concussive syndrome with persisting neurological, cognitive and neuropsychiatric symptoms. CTE was once thought to be unique to boxers, but it has now been observed in many different athletes having suffered multiple concussions as well as in military personal after repeated blast injuries. Much remains unknown about the development of CTE but its pathological substrate is usually tau, similar to that seen in Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD). The aim of this "perspective" is to compare and contrast clinical and pathological CTE with the other neurodegenerative proteinopathies and highlight that there is an urgent need for understanding the relationship between concussion and the development of CTE as it may provide a window into the development of a proteinopathy and thus new avenues for treatment.

  17. Chronic Traumatic Encephalopathy: The Impact on Athletes

    PubMed Central

    Cantu, Robert; Chin, Lawrence S.

    2016-01-01

    Chronic traumatic encephalopathy (CTE) is a devastating neuropsychological condition afflicting a small percentage of athletes partaking in high-impact sports. The onset of symptoms lags years behind the inciting events. Repetitive minor head injuries are felt to be the main etiology behind CTE. Routine radiographic imaging generally is unremarkable in cases of CTE. Functional magnetic resonance imaging (fMRI), magnetic resonance spectroscopy (MRS), and diffusion tensor imaging (DTI) are advanced MRI-based sequences that have shown promise in detecting early radiographic findings that may be reflective of CTE. Progressive neuronal loss is the histopathological hallmark of this neurodegenerative disease. Strategizing earlier detection techniques is paramount in delivering optimal care to athletes afflicted with CTE. PMID:27088064

  18. Leucine metabolism in patients with Hepatic Encephalopathy

    SciTech Connect

    McGhee, A.S.; Kassouny, M.E.; Matthews, D.E.; Millikan, W.

    1986-03-01

    A primed continuous infusion of (/sup 15/N, 1-/sup 13/C)leucine was used to determine whether increased oxidation and/or protein synthesis of leucine occurs in patients with cirrhosis. Five controls and patients were equilibrated on a metabolic balance diet (0.6 g protein per kg ideal body weight (IBW)). An additional four patients were equilibrated in the same manner with the same type of diet with a protein level of 0.75 g per kg IBW. Plasma leucine and breath CO/sub 2/ enrichments were measured by mass spectrometry. Protein synthesis and leucine metabolism were identical in controls and patients when both were fed a diet with 0.6 g protein/kg IBW. Results indicate that systemic derangements of leucine metabolism are not the cause of Hepatic Encephalopathy.

  19. Subacute necrotising encephalopathy in an Alaskan husky.

    PubMed

    Wakshlag, J J; de Lahunta, A; Robinson, T; Cooper, B J; Brenner, O; O'Toole, T D; Olson, J; Beckman, K B; Glass, E; Reynolds, A J

    1999-12-01

    A 29-month-old female Alaskan husky was presented recumbent, tetraparetic and in a state of dementia, with blindness and cranial nerve deficits. The dog's progress was followed for over two months, as the signs resolved to an non-progressive mild hypermetria with slight proprioceptive ataxia, a diminished menace response and inability to prehend food. Magnetic resonance imaging (MRI) revealed bilateral cavitation extending from the thalamus to the medulla, with less pronounced degenerative lesions in the caudate nucleus, putamen and claustrum. Cerebrospinal fluid lactate and pyruvate concentrations were in their normal ranges. Necropsy and histological examination confirmed the MRI findings as well as neuronal degeneration of the cerebellar cortex in the vermis and degenerative changes in the neocortex at the depths of the cerebral sulci. In view of the similarity of lesions to subacute necrotising encephalomyelopathy, known as Leigh's disease in humans, a tentative diagnosis of a mitochondrial encephalopathy was made.

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

    PubMed

    Orlov, Sergey; Goncharova, Iryna; Urbanová, Marie

    2014-05-21

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

  1. Combined Effects of Smoking and Bilirubin Levels on the Risk of Lung Cancer in Korea: The Severance Cohort Study

    PubMed Central

    Lim, Jung-eun; Kimm, Heejin; Jee, Sun Ha

    2014-01-01

    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. PMID:25100210

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

    PubMed

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

    2016-06-01

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

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

    PubMed

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

    2015-03-01

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

  4. Prion biology relevant to bovine spongiform encephalopathy.

    PubMed

    Novakofski, J; Brewer, M S; Mateus-Pinilla, N; Killefer, J; McCusker, R H

    2005-06-01

    Bovine spongiform encephalopathy (BSE) and chronic wasting disease (CWD) of deer and elk are a threat to agriculture and natural resources, as well as a human health concern. Both diseases are transmissible spongiform encephalopathies (TSE), or prion diseases, caused by autocatalytic conversion of endogenously encoded prion protein (PrP) to an abnormal, neurotoxic conformation designated PrPsc. Most mammalian species are susceptible to TSE, which, despite a range of species-linked names, is caused by a single highly conserved protein, with no apparent normal function. In the simplest sense, TSE transmission can occur because PrPsc is resistant to both endogenous and environmental proteinases, although many details remain unclear. Questions about the transmission of TSE are central to practical issues such as livestock testing, access to international livestock markets, and wildlife management strategies, as well as intangible issues such as consumer confidence in the safety of the meat supply. The majority of BSE cases seem to have been transmitted by feed containing meat and bone meal from infected animals. In the United Kingdom, there was a dramatic decrease in BSE cases after neural tissue and, later, all ruminant tissues were banned from ruminant feed. However, probably because of heightened awareness and widespread testing, there is growing evidence that new variants of BSE are arising "spontaneously," suggesting ongoing surveillance will continue to find infected animals. Interspecies transmission is inefficient and depends on exposure, sequence homology, TSE donor strain, genetic polymorphism of the host, and architecture of the visceral nerves if exposure is by an oral route. Considering the low probability of interspecies transmission, the low efficiency of oral transmission, and the low prion levels in nonnervous tissues, consumption of conventional animal products represents minimal risk. However, detection of rare events is challenging, and TSE

  5. Quantitative Risk Assessment of Bovine Spongiform Encephalopathy

    NASA Astrophysics Data System (ADS)

    Tsutsui, Toshiyuki; Kasuga, Fumiko

    Bovine spongiform encephalopathy (BSE) is a progressive neurological disease of cattle affecting the central nervous system and was first diagnosed in the United Kingdom (UK) in 1986 (Wells et al., 1987). This disease is one of the transmissible spongiform encephalopathy (TSE) which includes Creutzfeldt-Jakob disease (CJD) in humans and scrapie in sheep. The causative agent of TSE is considered to be an abnormal form of prion protein. However, the details of its pathogenic mechanism have not been fully identified. Scrapie, which causes neurological symptoms in sheep and goats, has existed in the UK for 200 years (Hoinville, 1996) and spread across the rest of the world in the 1900s (Detwiler & Baylis, 2003). There has been no report so far that scrapie can be transmitted to humans. Initially, BSE was also considered as a disease affecting only animals. However, a variant type of Creutzfeldt-Jakob disease (vCJD) was first reported in the UK, and exposure to a BSE agent was suspected (Collinge, Sidle, Meads, Ironside, & Hill, 1996). vCJD is clinically and pathologically different from the sporadic type of CJD, and age at clinical onset of vCJD is younger than sporadic type (Will et al., 1996). Since the UK government announced the possible association between BSE and vCJD in 1996, BSE has become a huge public health concern all over the world. Of particular concern about vCJD, the fatal disease in younger age, distorted consumer confidence in beef safety, and as a result reduced beef consumption has been seen in many BSE-affected countries.

  6. Brain proton magnetic resonance spectroscopy for hepatic encephalopathy

    NASA Astrophysics Data System (ADS)

    Ong, Chin-Sing; McConnell, James R.; Chu, Wei-Kom

    1993-08-01

    Liver failure can induce gradations of encephalopathy from mild to stupor to deep coma. The objective of this study is to investigate and quantify the variation of biochemical compounds in the brain in patients with liver failure and encephalopathy, through the use of water- suppressed, localized in-vivo Proton Magnetic Resonance Spectroscopy (HMRS). The spectral parameters of the compounds quantitated are: N-Acetyl Aspartate (NAA) to Creatine (Cr) ratio, Choline (Cho) to Creatine ratio, Inositol (Ins) to Creatine ratio and Glutamine-Glutamate Amino Acid (AA) to Creatine ratio. The study group consisted of twelve patients with proven advanced chronic liver failure and symptoms of encephalopathy. Comparison has been done with results obtained from five normal subjects without any evidence of encephalopathy or liver diseases.

  7. Genetics Home Reference: MECP2-related severe neonatal encephalopathy

    MedlinePlus

    ... onset encephalopathy with microcephaly Patient Support and Advocacy Resources (2 links) Rare Disease Clinical Research Network: Rett Syndrome, MECP2 Duplication and Rett-Related Disorders Natural History Study RettSyndrome.org GeneReviews (1 link) MECP2- ...

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

    PubMed

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

    2014-07-01

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

  9. Early progressive encephalopathy in boys and MECP2 mutations.

    PubMed

    Kankirawatana, P; Leonard, H; Ellaway, C; Scurlock, J; Mansour, A; Makris, C M; Dure, L S; Friez, M; Lane, J; Kiraly-Borri, C; Fabian, V; Davis, M; Jackson, J; Christodoulou, J; Kaufmann, W E; Ravine, D; Percy, A K

    2006-07-11

    MECP2 mutations mainly occur in females with Rett syndrome. Mutations have been described in 11 boys with progressive encephalopathy: seven of nine with affected sisters and two de novo. The authors report four de novo occurrences: three pathogenic and one potentially pathogenic. Common features include failure to thrive, respiratory insufficiency, microcephaly, and abnormal motor control. MECP2 mutations should be assessed in boys with progressive encephalopathy and one or more of respiratory insufficiency, abnormal movements or tone, and intractable seizures.

  10. Spongiform encephalopathy in a captive puma (Felis concolor).

    PubMed

    Willoughby, K; Kelly, D F; Lyon, D G; Wells, G A

    1992-11-01

    A captive adult puma developed ataxia, a hypermetric gait and whole body tremor. The signs progressed over a period of six weeks. Histopathological examination following euthanasia demonstrated spongiform encephalopathy, gliosis and mild non-suppurative meningoencephalitis. Immunostaining with a polyclonal antiserum revealed prion protein (PrP) associated with these changes in sections of cervical spinal cord and medulla. This is the first confirmed case of a scrapie-like spongiform encephalopathy described in a non-domestic cat in the United Kingdom.

  11. Refining the ammonia hypothesis: a physiology-driven approach to the treatment of hepatic encephalopathy.

    PubMed

    Tapper, Elliot B; Jiang, Z Gordon; Patwardhan, Vilas R

    2015-05-01

    Hepatic encephalopathy (HE) is one of the most important complications of cirrhosis and portal hypertension. Although the etiology is incompletely understood, it has been linked to ammonia directly and indirectly. Our goal is to review for the clinician the mechanisms behind hyperammonemia and the pathogenesis of HE to explain the rationale for its therapy. We reviewed articles collected through a search of MEDLINE/PubMed, Cochrane Database of Systematic Reviews, and Google Scholar between October 1, 1948, and December 8, 2014, and by a manual search of citations within retrieved articles. Search terms included hepatic encephalopathy, ammonia hypothesis, brain and ammonia, liver failure and ammonia, acute-on-chronic liver failure and ammonia, cirrhosis and ammonia, portosytemic shunt, ammonia and lactulose, rifaximin, zinc, and nutrition. Ammonia homeostatsis is a multiorgan process involving the liver, brain, kidneys, and muscle as well as the gastrointestinal tract. Indeed, hyperammonemia may be the first clue to poor functional reserves, malnutrition, and impending multiorgan dysfunction. Furthermore, the neuropathology of ammonia is critically linked to states of systemic inflammation and endotoxemia. Given the complex interplay among ammonia, inflammation, and other factors, ammonia levels have questionable utility in the staging of HE. The use of nonabsorbable disaccharides, antibiotics, and probiotics reduces gut ammoniagenesis and, in the case of antibiotics and probiotics, systemic inflammation. Nutritional support preserves urea cycle function and prevents wasting of skeletal muscle, a significant site of ammonia metabolism. Correction of hypokalemia, hypovolemia, and acidosis further assists in the reduction of ammonia production in the kidney. Finally, early and aggressive treatment of infection, avoidance of sedatives, and modification of portosystemic shunts are also helpful in reducing the neurocognitive effects of hyperammonemia. Refining the

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

    PubMed

    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 <2-year medical history and no treatment), serum IBIL and 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.

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

    PubMed Central

    Vítek, Libor

    2012-01-01

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

  14. Persistence of Cognitive Impairment after Resolution of Overt Hepatic Encephalopathy

    PubMed Central

    Bajaj, Jasmohan S; Schubert, Christine M; Heuman, Douglas M; Wade, James B; Gibson, Douglas P; Topaz, Allyne; Saeian, Kia; Hafeezullah, Muhammad; Bell, Debulon E; Sterling, Richard K; Stravitz, R Todd; Luketic, Velimir; White, Melanie B; Sanyal, Arun J

    2010-01-01

    Background & Aims In patients with cirrhosis, hepatic encephalopathy (HE) has acute but reversible as well as chronic components. We investigated the extent of residual cognitive impairment following clinical resolution of overt HE (OHE). Methods Cognitive function of cirrhotic patients was evaluated using psychometric tests (digit symbol [DS], block design [BD], and number connection [NCT-A&B]) and the inhibitory control test (ICT). Improvement (reduction) in ICT lures and 1st minus 2nd halves (ΔL1–2) were used to determine learning of response inhibition. Two cross-sectional studies (A and B) compared data from stable cirrhotics, with or without prior OHE. We then prospectively assessed cognitive performance, before and after the first episode of OHE. Results In study A, (226 cirrhotic patients) 54 had experienced OHE, 120 had minimal HE and 52 with no minimal HE. Despite normal mental status on lactulose after OHE, cirrhotics were cognitively impaired, based on results from all tests. Learning of response inhibition (ΔL1–2 ≥1), was evident in patients with minimal HE and no minimal HE, but was lost after OHE. In study B (50 additional patients who developed ≥1 documented OHE episode during follow-up), the number of OHE hospitalizations correlated with severity of residual impairment, indicated by ICT lures (r=0.5, P=0.0001), DST (r=−0.39, P=0.002) and NCT-B (r=0.33, P=0.04). In the prospective study (59 cirrhotics without OHE), 15 developed OHE; ICT lure response worsened significantly after OHE (12 before vs.18 after, P=0.0003) and learning of response inhibition was lost. The 44 patients who did not experience OHE did not have deteriorations in cognitive function in serial testing. Conclusion In cirrhosis, episodes of OHE are associated with persistent and cumulative deficits in working memory, response inhibition, and learning. PMID:20178797

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

    PubMed Central

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

    2016-01-01

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

  16. Acute viral hepatitis E presenting with haemolytic anaemia and acute renal failure in a patient with glucose-6-phosphate dehydrogenase deficiency.

    PubMed

    Tomar, Laxmikant Ramkumarsingh; Aggarwal, Amitesh; Jain, Piyush; Rajpal, Surender; Agarwal, Mukul P

    2015-10-01

    The association of acute hepatitis E viral (HEV) infection with glucose-6-phosphate dehydrogenase (G6PD) deficiency leading to extensive intravascular haemolysis is a very rare clinical entity. Here we discuss such a patient, who presented with acute HEV illness, developed severe intravascular haemolysis and unusually high levels of bilirubin, complicated by acute renal failure (ARF), and was later on found to have a deficiency of G6PD. The patient recovered completely with haemodialysis and supportive management. PMID:25500531

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

  19. Substantial Effect of Efavirenz Monotherapy on Bilirubin Levels in Healthy Volunteers

    PubMed Central

    Metzger, Ingrid F.; Quigg, Troy C.; Epstein, Noam; Aregbe, Abdulateef O.; Thong, Nancy; Callaghan, John T.; Flockhart, David A.; Nguyen, Anne T.; Stevens, Colleen K.; Gupta, Samir K.; Desta, Zeruesenay

    2014-01-01

    Background Efavirenz exhibits multiple interactions with drug-metabolizing enzymes and transporters, and for this reason efavirenz-based HIV therapy is associated with altered pharmacokinetics of coadministered drugs. Probably by the same mechanism, efavirenz-based HIV therapy affects the disposition of endogenous compounds, but this effect is difficult to directly link with efavirenz because it is used in combination with other drugs. Objectives To explore the effect of efavirenz monotherapy on biochemical laboratory values in a clinical trial of healthy volunteers. Methods Men and women (aged 18–49 years) with body mass index ≤32 who were assessed to be healthy based on medical history, physical examination, and standard laboratory screening received a single (600 mg) and multiple doses (600 mg/d for 17 days) of efavirenz orally. This trial was designed to determine the pharmacokinetics and drug interactions of efavirenz. As part of this study, analysis of serum chemistries that were measured at study entry (screening) and 1 week after completion of the multiple dose study (exit) is reported. Results Data from 60 subjects who fully completed and 13 subjects who partially completed the study are presented. Total bilirubin was substantially reduced at exit (by ~30%, with large intersubject variability) compared with screening values (P < 0.0001). The percent changes were in part explained by the intersubject differences in baseline total bilirubin because there was a significant correlation between baseline (screening) values and percent change at exit (r = 0.50; P < 0.0001). Hemoglobin and absolute neutropenia were also substantially decreased at exit compared with screening, but this may be due to intensive blood sampling rather than direct effect of efavirenz on these parameters. No significant correlation was found between percent change in hemoglobin versus percent change in bilirubin, indicating the effect of efavirenz on bilirubin is independent of its

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

    SciTech Connect

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

    2011-11-15

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

  1. An Evaluation of Cerebral and Systemic Predictors of 18-Month Outcomes for Neonates With Hypoxic Ischemic Encephalopathy.

    PubMed

    Shellhaas, Renée A; Kushwaha, Juhi S; Plegue, Melissa A; Selewski, David T; Barks, John D E

    2015-10-01

    Amplitude-integrated EEG (aEEG) is a commonly used predictor of outcome after hypoxic ischemic encephalopathy. Cerebral and systemic near-infrared spectroscopy and acute kidney injury might also have prognostic value. The authors monitored neonates with aEEG, cerebral and systemic near-infrared spectroscopy during therapeutic hypothermia, assigned an acute kidney injury stage, and measured neurodevelopmental outcome. For 18 infants, cerebral near-infrared spectroscopy variables did not differentiate between those with favorable (n = 13) versus adverse (death or moderate-severe disability; n = 5) 18-month outcomes. However, systemic rSO2 variability was higher during hours 48-72 of cooling among those with favorable outcomes (.02 < P < .03). Mean aEEG amplitude during hours 24 to 48 of cooling was higher among those with good outcomes (.027 < P < .032). The aEEG lower margin was also higher during hours 12 to 48 for those with good outcomes (.014 < P < .035). Acute kidney injury did not predict outcome (P > .05). aEEG is a useful prognostic tool for outcomes after neonatal hypoxic ischemic encephalopathy, but the role of near-infrared spectroscopy in the hypothermia-treated population remains uncertain.

  2. An Evaluation of Cerebral and Systemic Predictors of 18-Month Outcomes for Neonates With Hypoxic Ischemic Encephalopathy.

    PubMed

    Shellhaas, Renée A; Kushwaha, Juhi S; Plegue, Melissa A; Selewski, David T; Barks, John D E

    2015-10-01

    Amplitude-integrated EEG (aEEG) is a commonly used predictor of outcome after hypoxic ischemic encephalopathy. Cerebral and systemic near-infrared spectroscopy and acute kidney injury might also have prognostic value. The authors monitored neonates with aEEG, cerebral and systemic near-infrared spectroscopy during therapeutic hypothermia, assigned an acute kidney injury stage, and measured neurodevelopmental outcome. For 18 infants, cerebral near-infrared spectroscopy variables did not differentiate between those with favorable (n = 13) versus adverse (death or moderate-severe disability; n = 5) 18-month outcomes. However, systemic rSO2 variability was higher during hours 48-72 of cooling among those with favorable outcomes (.02 < P < .03). Mean aEEG amplitude during hours 24 to 48 of cooling was higher among those with good outcomes (.027 < P < .032). The aEEG lower margin was also higher during hours 12 to 48 for those with good outcomes (.014 < P < .035). Acute kidney injury did not predict outcome (P > .05). aEEG is a useful prognostic tool for outcomes after neonatal hypoxic ischemic encephalopathy, but the role of near-infrared spectroscopy in the hypothermia-treated population remains uncertain. PMID:25724376

  3. Topiramate increases the risk of valproic acid-induced encephalopathy.

    PubMed

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

    2013-01-01

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

  4. Neuropsychological sequelae of Wernicke's encephalopathy in a 20-year-old woman: selective impairment of a frontal memory system.

    PubMed

    Parkin, A J; Dunn, J C; Lee, C; O'Hara, P F; Nussbaum, L

    1993-01-01

    This article reports the neuropsychological sequelae of Wernicke's Encephalopathy in a 20-year-old woman. After amelioration of acute symptoms, the patient showed a range of cognitive impairments the most marked of which was a severe impairment on free recall tasks involving both verbal and nonverbal material. In contrast, recognition memory appeared remarkably well preserved. Some evidence of frontal lobe and general intellectual impairment was also noted. The case is discussed in terms of the pathophysiology of Wernicke-Korsakoff Syndrome, criteria for its diagnosis, and the multicomponent nature of memory deficits.

  5. 78 FR 11207 - Transmissible Spongiform Encephalopathies Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-15

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Transmissible Spongiform Encephalopathies Advisory Committee... be open to the public. Name of Committee: Transmissible Spongiform Encephalopathies...

  6. The Neuropathology of Chronic Traumatic Encephalopathy

    PubMed Central

    McKee, Ann C.; Stein, Thor D.; Kiernan, Patrick T.; Alvarez, Victor E.

    2015-01-01

    Repetitive brain trauma is associated with a progressive neurological deterioration, now termed as chronic traumatic encephalopathy (CTE). Most instances of CTE occur in association with the play of sports, but CTE has also been reported in association with blast injuries and other neurotrauma. Symptoms of CTE include behavioral and mood changes, memory loss, cognitive impairment and dementia. Like many other neurodegenerative diseases, CTE is diagnosed with certainty only by neuropathological examination of brain tissue. CTE is a tauopathy characterized by the deposition of hyperphosphorylated tau (p-tau) protein as neurofibrillary tangles, astrocytic tangles and neurites in striking clusters around small blood vessels of the cortex, typically at the sulcal depths. Severely affected cases show p-tau pathology throughout the brain. Abnormalities in phosphorylated 43 kDa TAR DNA-binding protein are found in most cases of CTE; beta-amyloid is identified in 43%, associated with age. Given the importance of sports participation and physical exercise to physical and psychological health as well as disease resilience, it is critical to identify the genetic risk factors for CTE as well as to understand how other variables, such as stress, age at exposure, gender, substance abuse and other exposures, contribute to the development of CTE. PMID:25904048

  7. Benign encephalopathy of pregnancy. Preliminary clinical observations.

    PubMed

    Poser, C M; Kassirer, M R; Peyser, J M

    1986-01-01

    A survey of 67 pregnancies in 51 professional women (physicians, psychologists, nurses, administrators, etc.) revealed the occurrence of symptoms of cognitive dysfunction such as forgetfulness, disorientation, confusion and reading difficulties in 28 pregnancies occurring in 21 women. These were unrelated to such factors as age of delivery, percentage weight gain, the baby's sex or birth weight, alcohol consumption, smoking, a history of migraine or allergy or other symptoms occurring during pregnancy such as sleepiness and lack of concentration, irritability, loss of interest in job or nightmares. Nor was there any correlation with hypertension, proteinuria, glycosuria, ketonuria, anemia, or morning sickness. Furthermore, these cognitive disturbances were not related to depression or sleep deprivation. Despite these symptoms, none of the women suffering from them were forced to interrupt their professional activities during pregnancy. The syndrome of benign encephalopathy of pregnancy should be recognized so that simple precautions can be taken to prevent any interference with professional or other activities. The etiology of the syndrome is unknown.

  8. A critical review of chronic traumatic encephalopathy.

    PubMed

    Iverson, Grant L; Gardner, Andrew J; McCrory, Paul; Zafonte, Ross; Castellani, Rudy J

    2015-09-01

    Chronic traumatic encephalopathy (CTE) has been described in the literature as a neurodegenerative disease with: (i) localized neuronal and glial accumulations of phosphorylated tau (p-tau) involving perivascular areas of the cerebral cortex, sulcal depths, and with a preference for neurons within superficial cortical laminae; (ii) multifocal axonal varicosities and axonal loss involving deep cortex and subcortical white matter; (iii) relative absence of beta-amyloid deposits; (iv) TDP-43 immunoreactive inclusions and neurites; and (v) broad and diverse clinical features. Some of the pathological findings reported in the literature may be encountered with age and other neurodegenerative diseases. However, the focality of the p-tau cortical findings in particular, and the regional distribution, are believed to be unique to CTE. The described clinical features in recent cases are very similar to how depression manifests in middle-aged men and with frontotemporal dementia as the disease progresses. It has not been established that the described tau pathology, especially in small amounts, can cause complex changes in behavior such as depression, substance abuse, suicidality, personality changes, or cognitive impairment. Future studies will help determine the extent to which the neuropathology is causally related to the diverse clinical features. PMID:26183075

  9. Posterior Reversible Encephalopathy Syndrome Complicating Traumatic Pancreatitis

    PubMed Central

    Sigurtà, Anna; Terzi, Valeria; Regna-Gladin, Caroline; Fumagalli, Roberto

    2016-01-01

    Abstract We are reporting a case of posterior reversible encephalopathy syndrome (PRES) developed in an unusual clinical scenario without the presence of the most described symptoms. PRES is a neurological and radiological syndrome described in many different clinical conditions. In children it has been mostly reported in association with hematological and renal disorders. Our patient was a 15 years old boy, admitted to our intensive care unit for pancreatitis after blunt abdominal trauma. During the stay in the intensive care unit, he underwent multiple abdominal surgical interventions for pancreatitis complications. He had a difficult management of analgesia and sedation, being often agitated with high arterial pressure, and he developed a bacterial peritonitis. After 29 days his neurological conditions abruptly worsened with neuroimaging findings consistent with PRES. His clinical conditions progressively improved after sedation and arterial pressure control. He was discharged at home with complete resolution of the neurological and imaging signs 2 months later. The pathophysiology of PRES is controversial and involves disordered autoregulation ascribable to hypertension and endothelial dysfunction. In this case both hypertension and endothelial activation, triggered by sepsis and pancreatitis, could represent the culprits of PRES onset. Even if there is no specific treatment for this condition, a diagnosis is mandatory to start antihypertensive and supportive treatment. We are therefore suggesting to consider PRES in the differential diagnosis of a neurological deterioration preceded by hypertension and/or septic state, even without other “typical” clinical features. PMID:27258506

  10. Mycophenolate-Induced Posterior Reversible Encephalopathy Syndrome.

    PubMed

    Khajuria, Bhavik; Khajuria, Mansi; Agrawal, Yashwant

    2016-01-01

    A 29-year-old woman presented with diffuse anasarca and shortness of breath. Workup revealed a creatinine of 3.3 and a glomerular filtration rate of 17. The patient was also found to be pancytopenic with evidence of hemolytic anemia. A renal biopsy showed evidence of stage IV lupus nephritis with rapidly progressive glomerulonephritis. Her lupus was further classified as ANA negative and anti-dsDNA positive. Mycophenolate and triweekly hemodialysis were started along with a steroid burst of methylprednisolone 1 g for 3 days followed by prednisone 60 mg daily. Four days after discharge, the patient represented with a witnessed 3-minute seizure involving bowel incontinence, altered mental status, and tongue biting. She was given 2 mg intravenous lorazepam and loaded with 1000 mg levetiracetam for seizure prophylaxis. Magnetic resonance imaging of the head revealed bilateral posterior hemispheric subcortical edema, and the diagnosis of posterior reversible encephalopathy syndrome was made. Mycophenolate was immediately discontinued and replaced with cyclophosphamide. Strict blood pressure control below 140/90 mm Hg was maintained initially with intravenous nicardipine drip and then transitioned to oral nifedipine, clonidine, losartan, and minoxidil. A repeat head magnetic resonance imaging 8 days later showed resolved subcortical edema consistent with the patient's improved mental status. No permanent neurologic sequelae were recorded as a result of this hospital episode. PMID:25933141

  11. Sodium Benzoate for Treatment of Hepatic Encephalopathy

    PubMed Central

    Misel, Michael L.; Patton, Heather; Mendler, Michel

    2013-01-01

    Hepatic encephalopathy (HE) is a serious but usually reversible neuropsychiatric complication of cirrhosis, inborn errors of metabolism involving disorders of the urea cycle, and noncirrhotic portosystemic shunting that most commonly arises from a transjugular intrahepatic portosystemic shunting procedure. Symptoms can include alterations in cognitive function, neuromuscular activity, and consciousness, as well as sleep disorders and mood changes. HE is associated with significant morbidity and mortality and, if not properly treated, will lead to increased hospital admissions and healthcare costs. Although the standard therapies of lactulose and rifaximin (Xifaxan, Salix) are effective for most patients, these drugs may be associated with significant adverse effects and expense and, in some patients, inadequate therapeutic response. A need for adjunctive therapies exists. Drugs that target serum and tissue ammonia metabolism and elimination may be important adjuncts to drugs that reduce ammonia production and absorption from the gastrointestinal tract for patients with severe or persistent overt symptoms of HE. Sodium benzoate is an inexpensive adjunctive agent that can be used in addition to lactulose and rifaximin and may provide an option for some select patients with refractory HE who have failed to respond to standard therapies or who cannot afford them. Although sodium benzoate does not share the same adverse effect profiles of standard therapies for HE, its efficacy has not been well established. Given the significant dose-dependent sodium content of this therapy, it may not be appropriate for patients with significant fluid retention or kidney dysfunction. PMID:24711766

  12. Antibody-Mediated Autoimmune Encephalopathies and Immunotherapies.

    PubMed

    Gastaldi, Matteo; Thouin, Anaïs; Vincent, Angela

    2016-01-01

    Over the last 15 years it has become clear that rare but highly recognizable diseases of the central nervous system (CNS), including newly identified forms of limbic encephalitis and other encephalopathies, are likely to be mediated by antibodies (Abs) to CNS proteins. The Abs are directed against membrane receptors and ion channel-associated proteins that are expressed on the surface of neurons in the CNS, such as N-methyl D-aspartate receptors and leucine-rich, glioma inactivated 1 protein and contactin-associated protein like 2, that are associated with voltage-gated potassium channels. The diseases are not invariably cancer-related and are therefore different from the classical paraneoplastic neurological diseases that are associated with, but not caused by, Abs to intracellular proteins. Most importantly, the new antibody-associated diseases almost invariably respond to immunotherapies with considerable and sometimes complete recovery, and there is convincing evidence of their pathogenicity in the relatively limited studies performed so far. Treatments include first-line steroids, intravenous immunoglobulins, and plasma exchange, and second-line rituximab and cyclophosphamide, followed in many cases by steroid-sparing agents in the long-term. This review focuses mainly on N-methyl D-aspartate receptor- and voltage-gated potassium channel complex-related Abs in adults, the clinical phenotypes, and treatment responses. Pediatric cases are referred to but not reviewed in detail. As there have been very few prospective studies, the conclusions regarding immunotherapies are based on retrospective studies. PMID:26692392

  13. Differentiation of ruminant transmissible spongiform encephalopathy isolate types, including bovine spongiform encephalopathy and CH1641 scrapie.

    PubMed

    Jacobs, J G; Sauer, M; van Keulen, L J M; Tang, Y; Bossers, A; Langeveld, J P M

    2011-01-01

    With increased awareness of the diversity of transmissible spongiform encephalopathy (TSE) strains in the ruminant population, comes an appreciation of the need for improved methods of differential diagnosis. Exposure to bovine spongiform encephalopathy (BSE) has been associated with the human TSE, variant Creutzfeldt-Jakob disease, emphasizing the necessity in distinguishing low-risk TSE types from BSE. TSE type discrimination in ruminants such as cattle, sheep, goats and deer, requires the application of several prion protein (PrP)-specific antibodies in parallel immunochemical tests on brain homogenates or tissue sections from infected animals. This study uses in a single incubation step, three PrP-specific antibodies and fluorescent Alexa dye-labelled anti-mouse Fabs on a Western blot. The usual amount of brain tissue needed is 0.5 mg. This multiplex application of antibodies directed towards three different PrP epitopes enabled differential diagnosis of all established main features of classical scrapie, BSE and Nor98-like scrapie in sheep and goats, as well as the currently known BSE types C, H and L in cattle. Moreover, due to an antibody-dependent dual PrP-banding pattern, for the first time CH1641 scrapie of sheep can be reliably discriminated from the other TSE isolate types in sheep.

  14. Wernicke’s encephalopathy following Roux en Y gastric bypass surgery

    PubMed Central

    Zafar, Azra

    2015-01-01

    Wernicke’s encephalopathy (WE) is a serious neurological disorder characterized by a classical triad of acute mental confusion, ataxia, and opthalmoplegia due to thiamine deficiency. It was initially described in chronic alcoholics; however, any condition resulting in poor nutritional status places the patient at risk of WE. Bariatric surgery is now considered as an emergent cause of WE. The number of bariatric surgery is increasing for morbid obesity. We present a case of a 40-year-old male who presented with confusion and difficulty in maintaining the balance while walking 3 months after Roux en Y gastric bypass surgery. Diagnosis of WE was made on clinical ground and confirmed by magnetic resonance imaging of the brain, which showed bilateral hyperintense signals in paramedian thalami. Parenteral thiamine replacement was started, and patient showed complete recovery. PMID:26620994

  15. Iatrogenic Coagulopathy and the Development of Posterior Reversible Encephalopathy Syndrome after L-asparaginase Chemotherapy

    PubMed Central

    Rota, Eugenia; Vallisa, Daniele; Morelli, Nicola; Scagnelli, Paola

    2016-01-01

    Posterior reversible encephalopathy syndrome (PRES) is a clinical and radiological syndrome mostly related to hypertension, eclampsia, renal failure, or to chemotherapy and/or immunosuppressive drugs. Although the PRES pathophysiology is multifactorial, hypertension and endothelial dysfunction are hypothesized to be the pivotal factors. Here we report a case of PRES in an adult patient after chemotherapy (Escherichia coli L-asparaginase [L-ASP], daunorubicin, vincristine, and intrathecal methotrexate) for acute lymphoblastic leukemia. The development of the PRES was strictly associated with an iatrogenic coagulopathy induced by L-ASP, which inhibits the biosynthesis of hepatic coagulation factors. The nadir of platelet count, antithrombin III (ATIII) and fibrinogen curve was coincident with the onset of the PRES neurological picture; subsequently, the normalization of the ATIII and fibrinogen levels seemed to parallel the good clinical evolution. This case seems to provide new insights into the PRES pathophysiological mechanisms. PMID:27014503

  16. Atypical presentation of posterior reversible encephalopathy syndrome: Clinical and radiological characteristics in eclamptic patients

    PubMed Central

    Aracki-Trenkić, Aleksandra; Stojanov, Dragan; Trenkić, Milan; Radovanović, Zoran; Ignjatović, Jelena; Ristić, Saša; Trenkić-Bozinović, Marija

    2016-01-01

    Posterior reversible encephalopathy syndrome (PRES) is an obstetric emergency frequently occurring in a pregnant or puerperal woman, manifested with an acute headache, consciousness impairment, seizures, and visual deficits and is associated with white matter changes predominantly affecting the posterior parietal and occipital lobes of the brain. Apart from the above-described typical location of the changes, the most common atypical location involves the brain stem and basal ganglia. Since magnetic resonance imaging (MRI) is more sensitive and specific imaging technique compared to computerized tomography, establishing the diagnosis and follow-up in patients with PRES is based mainly on MRI findings. It is particularly important not to exclude PRES as a possible diagnosis when we have the appropriate clinical presentation accompanied by the atypical radiological findings, since this clinical-radiological syndrome can often be manifested with an atypical MRI image.

  17. Neuromyelitis Optica in Pregnancy Complicated by Posterior Reversible Encephalopathy Syndrome, Eclampsia and Fetal Death

    PubMed Central

    Igel, Catherine; Garretto, Diana; Robbins, Matthew S; Swerdlow, Michael; Judge, Nancy; Dayal, Ashlesha

    2015-01-01

    Neuromyelitis optica (NMO) is a demyelinating syndrome characterized by optic neuritis and acute myelitis with poor recovery and a progressive course. We report a poor outcome complicated by posterior reversible encephalopathy syndrome (PRES) and eclampsia and review available literature and current evidence for anticipation of adverse fetal and maternal effects. After a pregnancy complicated by multiple admissions for painful NMO exacerbations, a primiparous patient with seropositive NMO presented at 31 + 3/7 weeks with eclampsia, HELLP and subsequent fetal death. MRI confirmed PRES. NMO may be associated with eclampsia and leads to adverse maternal and fetal outcomes. Posited mechanisms include antibody-mediated placental damage and a heightened risk of eclampsia-associated PRES. Further characterization of the course of NMO and its relationship with pregnancy outcomes in larger series would be invaluable. PMID:25584107

  18. Atypical presentation of posterior reversible encephalopathy syndrome: Clinical and radiological characteristics in eclamptic patients.

    PubMed

    Aracki-Trenkić, Aleksandra; Stojanov, Dragan; Trenkić, Milan; Radovanović, Zoran; Ignjatović, Jelena; Ristić, Saša; Trenkić-Bozinović, Marija

    2016-08-01

    Posterior reversible encephalopathy syndrome (PRES) is an obstetric emergency frequently occurring in a pregnant or puerperal woman, manifested with an acute headache, consciousness impairment, seizures, and visual deficits and is associated with white matter changes predominantly affecting the posterior parietal and occipital lobes of the brain. Apart from the above-described typical location of the changes, the most common atypical location involves the brain stem and basal ganglia. Since magnetic resonance imaging (MRI) is more sensitive and specific imaging technique compared to computerized tomography, establishing the diagnosis and follow-up in patients with PRES is based mainly on MRI findings. It is particularly important not to exclude PRES as a possible diagnosis when we have the appropriate clinical presentation accompanied by the atypical radiological findings, since this clinical-radiological syndrome can often be manifested with an atypical MRI image. PMID:27483175

  19. Outcome After Therapeutic Hypothermia in Term Neonates with Encephalopathy and a Syndromic Diagnosis

    PubMed Central

    Mrelashvili, Anna; Bonifacio, Sonia L.; Rogers, Elizabeth E.; Shimotake, Thomas K.; Glass, Hannah C.

    2015-01-01

    The large randomized, controlled trials of therapeutic hypothermia for hypoxic-ischemic encephalopathy (HIE) excluded neonates with congenital disorders. The objective of this study was to report our experience using hypothermia in neonates with signs of HIE and a syndromic disorder or brain anomaly. Subjects were identified from a database of neonates admitted to the Neuro-Intensive Care Nursery at University of California, San Francisco. Of 169 patients fulfilling criteria for hypothermia, eight (5%) had a syndromic disorder, and were cooled as per guidelines for non-syndromic neonates. Perinatal characteristics of infants with and without syndromic disorder were not significantly different. Overall outcome was poor: 38% had evidence of acute HI injury, 3 subjects died, two survivors had low developmental quotient (DQ 25). The risk versus benefit of therapeutic hypothermia for HIE among neonates with congenital brain malformations or syndromic diagnoses is uncertain. PMID:25762585

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

    PubMed

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

    2005-08-01

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

  1. A spectroscopic study of the wavelength-dependent photoisomerizations of bilirubins bound to human serum albumin

    NASA Astrophysics Data System (ADS)

    Mazzoni, Marina; Agati, Giovanni; Pratesi, Riccardo; Persico, Maurizio

    2005-12-01

    The wavelength-dependent photoisomerizations of the asymmetric bilirubin BR-IXα and of the symmetric bilirubin-IIIα (BR-III) and mesobilirubin-XIIIα (MBR-XIII) bound to human serum albumin (HSA) in aqueous solution were analysed with the help of an exciton coupling model. The modelling was based on the absorption and circular dichroism (CD) spectra (bisignate Cotton effect). Time-dependent density functional theory (TD-DFT) of the free BR-IX molecule suggested the presence of two main bands of exciton coupling character in the blue region of the spectrum, and other weaker bands of charge transfer character at longer wavelengths. These peculiarities were taken into account to fit the photoisomerization quantum yields in the blue-green region as functions of the wavelength, obtaining the bandshape of the exciton coupling bands from the experimental CD spectra. The other excitons were extracted from the decomposition of the band resulting from the difference between the absorption spectrum and the sum (normalized-to-absorption) of the two CD excitons. We expressed photoisomerization quantum yields in terms of the sum of the contributions to photon absorption deriving from all the exciton states normalized to total absorption. For all the reversible photoprocesses of bilirubins and for the irreversible one of BR-IXα in HSA (i.e. lumirubin formation), we give reliable mean values of the individual state excitation probabilities and photoisomerization efficiencies in the pigment protein complex.

  2. Bilirubin adsorption on amine/methyl bifunctionalized SBA-15 with platelet morphology.

    PubMed

    Tang, Tao; Li, Xiaoan; Xu, Yao; Wu, Dong; Sun, Yuhan; Xu, Jun; Deng, Feng

    2011-06-01

    To remove bilirubin from human plasma, amine/methyl bifunctionalized SBA-15 materials were directly synthesized from the co-condensation of 3-aminopropylmethyldiethoxysilane and tetraethoxysilane with an amphiphilic block copolymer P123 as template. XRD, N(2) sorption analysis, FTIR and (29)Si MAS NMR were used to identify their well-ordered mesostructure and the grafting of amine and methyl groups on the surface of as-synthesized materials. Both SEM and TEM indicated that the bifunctionalized SBA-15 possessed platelet morphology. This might be attributed to the charge repulsion brought by protonated amine groups and the diminution of hydroxyl groups on the end of silicate-micelles, which passivated the end-to-end anchoring of silicate-micelles along the longitudinal axis. Such a material was investigated as the adsorbent for selective bilirubin removal from human plasma, which showed a high bilirubin clearance of 51.4% within 1.5 h with a little amount of albumin adsorption. The results of hemolysis assay suggested that the bifunctionalized SBA-15 caused serious hemolysis of red blood cells. However, in practical application, plasma separation technique could avoid direct contact between the adsorbent and red blood cells. The further hemeolysis assay proved that the plasma after contacting with the bifunctionalized SBA-15 could not lead to the hemolysis of red blood cells. Thus, the bifunctionalized SBA-15 is expected to be a potential candidate as a clinical hemoperfusion material. PMID:21382700

  3. Electroencephalogram of Age-Dependent Epileptic Encephalopathies in Infancy and Early Childhood

    PubMed Central

    Wong-Kisiel, Lily C.; Nickels, Katherine

    2013-01-01

    Epileptic encephalopathy syndromes are disorders in which the epileptiform abnormalities are thought to contribute to a progressive cerebral dysfunction. Characteristic electroencephalogram findings have an important diagnostic value in classification of epileptic encephalopathy syndromes. In this paper, we focus on electroencephalogram findings of childhood epileptic encephalopathy syndromes and provide sample illustrations. PMID:24024028

  4. 78 FR 72859 - Concurrence With OIE Risk Designations for Bovine Spongiform Encephalopathy

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-04

    ... spongiform encephalopathy (BSE) risk designations for 14 regions. The OIE recognizes these regions as being... ``Bovine Spongiform Encephalopathy; Importation of Bovines and Bovine Products,'' Docket No. APHIS-2008... regions for bovine spongiform encephalopathy (BSE) risk. Section 92.5 of the regulations provides that...

  5. Calcineurin Inhibitors Associated Posterior Reversible Encephalopathy Syndrome in Solid Organ Transplantation

    PubMed Central

    Song, Turun; Rao, Zhengsheng; Tan, Qiling; Qiu, Yang; Liu, Jinpeng; Huang, Zhongli; Wang, Xianding; Lin, Tao

    2016-01-01

    Abstract Posterior reversible encephalopathy syndrome (PRES) is a rare neurologic side effect of calcineurin inhibitors (CNIs) with poorly understood clinical features. We report cases of 2 patients with PRES developing after kidney transplantation and summarize PRES clinical features through a literature review. The 1st case was a 28-year-old man who received a kidney transplant from a deceased donor. Initial immunosuppressive therapy consisted of tacrolimus/mycophenolate mofetil/prednisolone. He developed headache and blurred vision with visual field loss15 days after transplantation and generalized seizures 4 days later. The 2nd case was a 34-year-old man who received a living kidney transplant. His initial immunosuppressive therapy comprised tacrolimus/mycophenolate mofetil/prednisolone. Two months after transplantation, he developed seizures. Both patients were diagnosed with PRES based on neurological symptoms and magnetic resonance imaging (MRI) findings; they recovered after switching from tacrolimus to either a cyclosporine or a lower tacrolimus dose. CNI-associated PRES is an acute neurological syndrome with seizures, encephalopathy, visual abnormalities, headache, focal neurological deficits, and nausea/vomiting. It is always accompanied by hypertension. A fluid-attenuated inversion recovery signal MRI scan typically shows reversible subcortical white matter changes in the posterior cerebral hemisphere that usually occur within the 1st month after transplantation. CNI-associated PRES has a generally favorable prognosis with early diagnosis and prompt treatment including alternating or discontinuing CNIs and blood pressure control. CNI-associated PRES should be considered in patients exhibiting acute neurological symptoms after transplantation. Early diagnosis and immediate treatment are critical for a favorable prognosis. PMID:27057842

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

    PubMed Central

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

    2016-01-01

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

  7. Measles-associated encephalopathy in children with renal transplants.

    PubMed

    Turner, A; Jeyaratnam, D; Haworth, F; Sinha, M D; Hughes, E; Cohen, B; Jin, L; Kidd, I M; Rigden, S P A; MacMahon, E

    2006-06-01

    Two children, boys of 8 and 13 years, presented with measles-associated encephalopathy several years after kidney transplantation for congenital nephrotic syndrome. In the absence of prior clinical measles, the neurological symptoms initially eluded diagnosis, but retrospective analysis of stored samples facilitated the diagnosis of measles-associated encephalopathy without recourse to biopsy of deep cerebral lesions. Each had received a single dose of measles mumps and rubella vaccine before 12 months of age. Prior vaccination, reduction of immunosuppression and treatment with intravenous immunoglobulin and ribavirin may have contributed to their survival. Persistent measles virus RNA shedding, present in one child, was not controlled by treatment with i.v. ribavirin. Two years later, both patients continue to have functioning allografts with only minimal immunosuppression. These cases illustrate the difficulty in diagnosing measles-associated encephalopathy in the immunocompromised host, even in the era of molecular diagnostics, and highlight the renewed threat of neurological disease in communities with incomplete herd immunity.

  8. Useful Tests for Hepatic Encephalopathy in Clinical Practice

    PubMed Central

    Nabi, Eiman; Bajaj, Jasmohan S

    2014-01-01

    Hepatic encephalopathy (HE) is a serious complication of liver disease and portosystemic shunting that represents a continuum of neuropsychiatric changes and altered consciousness. It is classified as overt hepatic encephalopathy (OHE) when clinically apparent or as covert hepatic encephalopathy (CHE) in its mildest form. Progression of CHE to OHE and its impact of quality of life make its early diagnosis imperative. Several diagnostic techniques ranging from simple clinical scales to sophisticated computerized tests exist yet diagnosis remains a challenge due to the time, cost and personnel involved. Psychometric tests appear promising due to their high sensitivity and low cost but results are variable depending on age and education. The pros and cons of current diagnostic methods for overt and covert HE are reviewed along with strategy to CHE testing. PMID:24357348

  9. Predictors of neonatal encephalopathy in full-term infants.

    PubMed Central

    Adamson, S. J.; Alessandri, L. M.; Badawi, N.; Burton, P. R.; Pemberton, P. J.; Stanley, F.

    1995-01-01

    OBJECTIVE--Preliminary investigation of the contribution of adverse antepartum and intrapartum factors to neonatal encephalopathy in singleton neonates born full term. DESIGN--Matched case-control study based on incidence density sampling of controls. SETTING--Two major teaching hospitals (one paediatric and one obstetric) and three peripheral maternity hospitals in Perth, Western Australia (population 1.2 million). SUBJECTS--89 cases, all the full term singleton neonates born during an eight month period in 1992 who fulfilled one or more of six criteria during the first week of life (seizures, abnormal conscious state, persistent hypertonia or hypotonia, and feeding or respiratory difficulties of central origin). One full term control infant without neonatal encephalopathy was matched to each case by sex, hospital of delivery, time of day and day of the week of birth, and maternal health insurance status. MAIN OUTCOME MEASURES--Odds ratio estimates of relative risk of neonatal encephalopathy associated with antepartum and intrapartum factors. RESULTS--Estimated incidence of moderate or severe encephalopathy in first week of life was 3.75 per 1000 full term live births. Thirteen cases and no controls had evidence suggestive of important intrapartum hypoxia, and in only five of these cases was the neurological condition at birth attributed to events during the intrapartum period. Univariate conditional logistic regression analysis identified significant differences between cases and controls for maternal vaginal bleeding in pregnancy, maternal thyroxine treatment, congenital abnormalities, induction of labour, interval from membrane rupture to delivery, maternal pyrexia in labour, augmentation of labour, abnormal intrapartum cardiotocograms, and meconium in labour. Family history of convulsions also approached significance. CONCLUSIONS--Our preliminary results suggest that intrapartum hypoxia, according to currently used criteria, was not the cause of neonatal

  10. Preclinical Models of Encephalopathy of Prematurity.

    PubMed

    Jantzie, Lauren L; Robinson, Shenandoah

    2015-01-01

    Encephalopathy of prematurity (EoP) encompasses the central nervous system (CNS) abnormalities associated with injury from preterm birth. Although rapid progress is being made, limited understanding exists of how cellular and molecular CNS injury from early birth manifests as the myriad of neurological deficits in children who are born preterm. More importantly, this lack of direct insight into the pathogenesis of these deficits hinders both our ability to diagnose those infants who are at risk in real time and could potentially benefit from treatment and our ability to develop more effective interventions. Current barriers to clarifying the pathophysiology, developmental trajectory, injury timing, and evolution include preclinical animal models that only partially recapitulate the molecular, cellular, histological, and functional abnormalities observed in the mature CNS following EoP. Inflammation from hypoxic-ischemic and/or infectious injury induced in utero in lower mammals, or actual prenatal delivery of more phylogenetically advanced mammals, are likely to be the most clinically relevant EOP models, facilitating translation to benefit infants. Injury timing, type, severity, and pathophysiology need to be optimized to address the specific hypothesis being tested. Functional assays of the mature animal following perinatal injury to mimic EoP should ideally test for the array of neurological deficits commonly observed in preterm infants, including gait, seizure threshold and cognitive and behavioral abnormalities. Here, we review the merits of various preclinical models, identify gaps in knowledge that warrant further study and consider challenges that animal researchers may face in embarking on these studies. While no one model system is perfect, insights relevant to the clinical problem can be gained with interpretation of experimental results within the context of inherent limitations of the chosen model system. Collectively, optimal use of multiple models

  11. Gut microbiota: its role in hepatic encephalopathy.

    PubMed

    Rai, Rahul; Saraswat, Vivek A; Dhiman, Radha K

    2015-03-01

    Ammonia, a key factor in the pathogenesis of hepatic encephalopathy (HE), is predominantly derived from urea breakdown by urease producing large intestinal bacteria and from small intestine and kidneys, where the enzyme glutaminases releases ammonia from circulating glutamine. Non-culture techniques like pyrosequencing of bacterial 16S ribosomal ribonucleic acid are used to characterize fecal microbiota. Fecal microbiota in patients with cirrhosis have been shown to alter with increasing Child-Turcotte-Pugh (CTP) and Model for End stage Liver Disease (MELD) scores, and with development of covert or overt HE. Cirrhosis dysbiosis ratio (CDR), the ratio of autochthonous/good bacteria (e.g. Lachnospiraceae, Ruminococcaceae and Clostridiales) to non-autochthonous/pathogenic bacteria (e.g. Enterobacteriaceae and Streptococcaceae), is significantly higher in controls and patients with compensated cirrhosis than patients with decompensated cirrhosis. Although their stool microbiota do not differ, sigmoid colonic mucosal microbiota in liver cirrhosis patients with and without HE, are different. Linkage of pathogenic colonic mucosal bacteria with poor cognition and inflammation suggests that important processes at the mucosal interface, such as bacterial translocation and immune dysfunction, are involved in the pathogenesis of HE. Fecal microbiome composition does not change significantly when HE is treated with lactulose or when HE recurs after lactulose withdrawal. Despite improving cognition and endotoxemia as well as shifting positive correlation of pathogenic bacteria with metabolites, linked to ammonia, aromatic amino acids and oxidative stress, to a negative correlation, rifaximin changes gut microbiome composition only modestly. These observations suggest that the beneficial effects of lactulose and rifaximin could be associated with a change in microbial metabolic function as well as an improvement in dysbiosis. PMID:26041954

  12. Prophylaxis and reversal of ifosfamide encephalopathy with methylene-blue.

    PubMed

    Küpfer, A; Aeschlimann, C; Wermuth, B; Cerny, T

    1994-03-26

    The antineoplastic ifosfamide produces dose-dependent signs of neurotoxicity. After ifosfamide overdose in a patient, we found excessive urinary excretion of glutaric acid and sarcosine, which is compatible with glutaric aciduria type II, a defect in mitochondrial fatty acid oxidation that results from defective electron transfer to flavoproteins. We therefore used the electron-accepting drug methylene-blue as an antidote for ifosfamide encephalopathy. In one patient, ifosfamide neurotoxicity was rapidly reversed by methylene-blue 50 mg intravenously. In another patient with previous episodes of ifosfamide encephalopathy, methylene-blue was administered orally prophylactically. No symptoms of neurotoxicity were noted.

  13. Toxic encephalopathy due to colchicine--Gloriosa superba poisoning.

    PubMed

    Gooneratne, Inuka Kishara; Weeratunga, Praveen; Caldera, Manjula; Gamage, Ranjanie

    2014-10-01

    Gloriosa superba, a flowering plant widespread in South and Southeast Asia, is implicated in many cases of self-poisoning. Colchicine is concentrated in the seeds and tubers and this mediates its toxicity. We describe a 28-year-old woman who developed delayed encephalopathy after eating G superba tubers. MR scan of brain showed bilateral symmetrical T2 basal ganglia hyperintensities in the caudate and lentiform nuclei. The delay in onset of encephalopathy is attributable to a direct-effect colchicine, probably mediated through its effect on microtubular transport.

  14. [Fever-induced refractory epileptic encephalopathy of children].

    PubMed

    Sivkova, S N; Bogdanov, E I; Zaĭkova, F M; Morozova, E A; Aiupova, V A; Zabbarova, A T; Shaĭmardanova, R M

    2013-01-01

    Fever-induced refractory epileptic encephalopathy of school-age children is a rare epileptic syndrome that causes difficulties in diagnosis at the initial stage of disease. It is characterized by sudden onset with multifocal refractory status epilepticus in previously healthy children with normal development. Later, children suffer from resistant focal epilepsy in the combination with cognitive deficit and behavioral difficulties. Authors describe a clinical case of fever-induced refractory epileptic encephalopathy of school-age children in a child of 7 years old. Aspects of etiology, pathogenesis, clinical manifestation, differential diagnosis, treatment and prognosis of the disease are discussed.

  15. Fatal Encephalopathy Associated with Influenza in a Health Care Professional.

    PubMed

    Kitano, Kiyoshi; Furuta, Kiyoshi; Kanai, Shinichiro; Takei, Yo-Ichi

    2016-01-01

    A 41-year-old nurse was referred to our hospital with a fever and disturbed consciousness. She tested positive for influenza antigen. CT and MRI findings revealed low density and intensity areas in the right occipital and lateral lobes with remarkable brain edema, which led to a diagnosis of influenza encephalopathy. Influenza A antibodies in the serum were below the detection limit despite the patient receiving previous vaccination three months earlier. A PCR analysis revealed that the influenza HA gene was classified into clade 3C.2a, subclass AH3N2. The present case indicates the potential development of encephalopathy in adults under certain conditions. PMID:26935378

  16. Neonatal Encephalopathy: Update on Therapeutic Hypothermia and Other Novel Therapeutics.

    PubMed

    McAdams, Ryan M; Juul, Sandra E

    2016-09-01

    Neonatal encephalopathy (NE) is a major cause of neonatal mortality and morbidity. Therapeutic hypothermia (TH) is standard treatment for newborns at 36 weeks of gestation or greater with intrapartum hypoxia-related NE. Term and late preterm infants with moderate to severe encephalopathy show improved survival and neurodevelopmental outcomes at 18 months of age after TH. TH can increase survival without increasing major disability, rates of an IQ less than 70, or cerebral palsy. Neonates with severe NE remain at risk of death or severe neurodevelopmental impairment. This review discusses the evidence supporting TH for term or near term neonates with NE. PMID:27524449

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

    PubMed Central

    Suraweera, Duminda; Sundaram, Vinay; Saab, Sammy

    2016-01-01

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

  18. Albumin dialysis with molecular adsorbent recirculating system (MARS) for the treatment of hepatic encephalopathy in liver failure.

    PubMed

    Kobashi-Margáin, Ramón A; Gavilanes-Espinar, Juan G; Gutiérrez-Grobe, Ylse; Gutiérrez-Jiménez, Angel A; Chávez-Tapia, Norberto; Ponciano-Rodríguez, Guadalupe; Uribe, Misael; Méndez Sánchez, Nahum

    2011-06-01

    Acute, acute-on-chronic and chronic liver diseases are major health issues worldwide, and most cases end with the need for liver transplantation. Up to 90% of the patients die waiting for an organ to be transplanted. Hepatic encephalopathy is a common neuropsychiatric syndrome that usually accompanies liver failure and impacts greatly on the quality of life. The molecular adsorbent recirculating system (MARS) is a recently developed form of artificial liver support that functions on a base of albumin dialysis. It facilitates the dialysis of albumin-bound and water-soluble toxins, allowing the patient to survive and even improving some clinical features of liver failure. The following manuscript reviews the technical features of MARS operation and some of the clinical trials that analyze the efficacy of the system in the therapy of liver diseases.

  19. Preclinical Models of Encephalopathy of Prematurity

    PubMed Central

    Jantzie, Lauren L.; Robinson, Shenandoah

    2015-01-01

    Encephalopathy of prematurity (EoP) encompasses the central nervous system (CNS) abnormalities associated with injury from preterm birth. Although rapid progress is being made, limited understanding exists of how the cellular and molecular CNS injury from early birth manifests as the myriad of neurological deficits in children who are born preterm. More importantly, this lack of direct insight into the pathogenesis of these deficits hinders both our ability to diagnose those infants who are at risk in real-time and could potentially benefit from treatment, and our ability to develop more effective interventions. Current barriers to clarifying the pathophysiology, developmental trajectory, injury timing and evolution include preclinical animal models that only partially recapitulate the molecular, cellular, histological and functional abnormalities observed in the mature CNS following EoP. Inflammation from hypoxic-ischemic and/or infectious injury induced in utero in lower mammals, or actual prenatal delivery of more phylogenetically-advanced mammals, are likely to be the most clinically relevant EOP models, facilitating translation to benefit infants. Injury timing, type, severity and pathophysiology need to be optimized to address the specific hypothesis being tested. Functional assays of the mature animal following perinatal injury to mimic EoP should ideally test for the array of neurological deficits commonly observed in preterm infants including gait, seizure threshold, cognitive and behavioral abnormalities. Here, we review the merits of various preclinical models, identify gaps in knowledge that warrant further study and consider challenges that animal researchers may face in embarking on these studies. While no one model system is perfect, insights relevant to the clinical problem can be gained with interpretation of experimental results within the context of inherent limitations of the chosen model system. Collectively, optimal use of multiple models will

  20. Bovine spongiform encephalopathy in Sweden: an H-type variant

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bovine spongiform encephalopathy (BSE) had never been detected in Sweden until 2006, when the active surveillance identified a case in a 12-year-old cow. The case was an unusual form since several molecular features of the protease-resistant prion protein (PrP**res) were different from classical BSE...

  1. Neuropsychiatric Manifestation of Hashimoto's Encephalopathy in an Adolescent and Treatment.

    PubMed

    Ransing, Ramdas Sarjerao; Mishra, Kshirod Kumar; Sarkar, Dipayan

    2016-01-01

    Hashimoto's encephalopathy is usually underdiagnosed and untreated because of complex neuropsychiatric manifestation. We report a case of an adolescent female with Hashimoto's encephalopathy who responded well to a combination of aspirin and levothyroxine. A 16-year-old girl presented at psychiatric emergency services with a depressive episode, menstrual irregularities, and a 5-month past history of thyroid swelling. On clinical examination, she was in a euthyroid state with insignificant neurological history. However, her previous investigation revealed a hypothyroid state. Her magnetic resonance imaging findings demonstrated infarcts in the bilateral gangliocapsular region and left frontal periventricular deep white matter lesion. Ultrasonography of the thyroid and fine needle aspiration cytology confirmed lymphocytic thyroiditis. Anti-thyroid peroxidase (289 IU/ml) antibody titer was elevated (289 IU/mL). Her depressive symptoms responded well to antidepressants, mood stabilizers, nonsteroidal anti-inflammatory drugs, and levothyroxine. She remained in the euthyroid state and then in the euthymic state for 3 years. Hashimoto's encephalopathy is steroid-responsive encephalopathy. Most researchers have observed a dramatic response to steroids with or without levothyroxine. A clinician may consider aspirin as an alternative to a steroid in long-term management to avoid steroid-related side effects and contraindications. PMID:27570351

  2. Recurring hyperammonemic encephalopathy induced by bacteria usually not producing urease

    PubMed Central

    2014-01-01

    Background Hyperammonemic encephalopathy may occur when urease-positive bacteria in the urinary tract produce ammonium which directly enters systemic circulation. Predisposing conditions such as a neurogenic bladder can increase both urinary tract infection and urine stagnation. Case presentation We describe the case of a 66 years old woman with a neurogenic bladder who twice developed hyperammonemic encephalopathy following urinary tract infection. During the second episode Escherichia coli and Enterococcus faecalis have been isolated in the urine. The neurologic examination showed psychomotor slowing, weak photomotor reflex, nystagmus in the lateral gaze and asterixis. The EEG showed triphasic waves which disappeared along with clinical recovery. Conclusion Escherichia coli and Enterococcus faecalis are commonly considered urease-negative bacteria. Although frequently involved in urinary tract infections, their role in causing hyperammonemic encephalopathy have not been previously reported. Moreover, despite only one case with a neurogenic bladder have been described so far, our is the first patient with reoccurring hyperammonemic encephalopathy secondary to urinary tract infections. PMID:24884855

  3. A rare case of glycine encephalopathy unveiled by valproate therapy.

    PubMed

    Subramanian, Velusamy; Kadiyala, Pramila; Hariharan, Praveen; Neeraj, E

    2015-01-01

    Glycine encephalopathy (GE) or nonketotic hyperglycinemia is an autosomal recessive disorder due to a primary defect in glycine cleavage enzyme system. It is characterized by elevated levels of glycine in plasma and cerebrospinal fluid usually presenting with seizures, hypotonia, and developmental delay. In our case, paradoxical increase in seizure frequency on starting sodium valproate led us to diagnose GE. PMID:26167219

  4. Neuropsychiatric Manifestation of Hashimoto's Encephalopathy in an Adolescent and Treatment

    PubMed Central

    Ransing, Ramdas Sarjerao; Mishra, Kshirod Kumar; Sarkar, Dipayan

    2016-01-01

    Hashimoto's encephalopathy is usually underdiagnosed and untreated because of complex neuropsychiatric manifestation. We report a case of an adolescent female with Hashimoto's encephalopathy who responded well to a combination of aspirin and levothyroxine. A 16-year-old girl presented at psychiatric emergency services with a depressive episode, menstrual irregularities, and a 5-month past history of thyroid swelling. On clinical examination, she was in a euthyroid state with insignificant neurological history. However, her previous investigation revealed a hypothyroid state. Her magnetic resonance imaging findings demonstrated infarcts in the bilateral gangliocapsular region and left frontal periventricular deep white matter lesion. Ultrasonography of the thyroid and fine needle aspiration cytology confirmed lymphocytic thyroiditis. Anti-thyroid peroxidase (289 IU/ml) antibody titer was elevated (289 IU/mL). Her depressive symptoms responded well to antidepressants, mood stabilizers, nonsteroidal anti-inflammatory drugs, and levothyroxine. She remained in the euthyroid state and then in the euthymic state for 3 years. Hashimoto's encephalopathy is steroid-responsive encephalopathy. Most researchers have observed a dramatic response to steroids with or without levothyroxine. A clinician may consider aspirin as an alternative to a steroid in long-term management to avoid steroid-related side effects and contraindications. PMID:27570351

  5. Metformin Inhibits Glutaminase Activity and Protects against Hepatic Encephalopathy

    PubMed Central

    Ampuero, Javier; Ranchal, Isidora; Nuñez, David; Díaz-Herrero, María del Mar; Maraver, Marta; del Campo, José Antonio; Rojas, Ángela; Camacho, Inés; Figueruela, Blanca; Bautista, Juan D.; Romero-Gómez, Manuel

    2012-01-01

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

  6. CADASIL: Migraine, Encephalopathy, Stroke and Their Inter-Relationships

    PubMed Central

    Markus, Hugh Stephen

    2016-01-01

    Background Migraine is common in Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) but its treatment responses are not well described, and its relationship to stroke risk unknown. Encephalopathy is a less common presentation; it has been suggested it is related to migraine. We characterised migraine patterns and treatment responses in CADASIL, and examined associations between migraine and both stroke risk and encephalopathy. Methods 300 symptomatic CADASIL patients were prospectively recruited from a national referral clinic over a nineteen year period, from 1996 to 2015. Data was collected using a standardised questionnaire. Migraine was classified according to the International Classification of Headache Disorders, 3rd edition (beta version). A cross-sectional analysis was carried out on the data collected. Results Migraine was present in 226 (75.3%), and the presenting feature in 203 (67.7%). It was usually accompanied by aura (89.8%). Patients showed variable responses to a variety of drugs for migraine. Of 24 given triptans, 45.5% had consistent or partial responses. None had complications following triptans. Thirty-three (11.0%) patients experienced encephalopathy lasting on average 8.1 ± 3.4 days. Patients with migraine with aura had higher odds of encephalopathy (OR = 5.4; 95%CI 1.6–28.4; p = 0.002). Patients with confusional aura had higher odds of encephalopathy than those with other aura types (OR = 2.5, 95%CI = 1.0–5.8, p = 0.04). There was also no increase in risk of encephalopathy with sex or age at onset of migraine. Migraineurs had a lower stroke risk than non-migraineurs (HR = 0.46, 95%CI 0.3–0.6, p = 2.1x10-6). Conclusions Migraine with aura is a prominent feature of CADASIL. Treatment responses are similar to those seen in the general migraine population and no complications were observed with triptans. Migraine with aura was associated with increased risk of encephalopathy suggesting

  7. Prognostic value of total bilirubin in patients with angina pectoris undergoing percutaneous coronary intervention

    PubMed Central

    Yao, Hai-Mu; Shen, De-Liang; Zhao, Xiao-Yan; Wang, Xiao-Fang; Sun, Tong-Wen; Zhang, Jin-Ying; Li, Ling; Zhao, Luo-Sha

    2015-01-01

    Background: Bilirubin is a potent antioxidant and previous studies have reported the relationship between low serum bilirubin concentration and atherosclerosis. Objective: To evaluate the prognostic value of serum total bilirubin (STB) in patients with angina pectoris undergoing percutaneous coronary intervention (PCI). Methods: In total of 1419 patients (931 men, mean age 60.9±10.5 years) with angina pectoris who had undergone successfully percutaneous coronary intervention (PCI) were included in this study. Patients were divided into 2 groups according to the median baseline STB (0.49 mg/dL in this cohort), which was measured before the PCI. Patients with a STB ≥0.49 mg/dL were classified into the high STB group and those with a STB <0.49 mg/dL were classified into the low STB group. Results: The incidence of in-hospital mortality and myocardial infraction was similar in the two groups. After a mean follow-up of 29.0±7.6 months, the incidence of death/myocardial infarction/stroke was significantly higher in low STB group compared with high STB group. Multivariate Cox regression analysis showed that low STB was an independent predictor of death/myocardial infarction/stroke (hazard ratio (HR) = 1.59, 95% confidence interval (CI) = 1.04-2.41, P = 0.031). The cumulative survival rate free from death/myocardial infarction/stroke was lower in low STB group than in high STB group (P = 0.002). Conclusion: Low STB levels before PCI is an independent predictor of long-term adverse clinical outcomes in patients with angina pectoris. PMID:26629096

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

    PubMed

    Rücker, Hannelore; Amslinger, Sabine

    2015-01-01

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

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

    SciTech Connect

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

    2015-01-01

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

  10. Hollow mesoporous carbon spheres with magnetic cores and their performance as separable bilirubin adsorbents.

    PubMed

    Guo, Limin; Cui, Xiangzhi; Li, Yongsheng; He, Qianjun; Zhang, Lingxia; Bu, Wenbo; Shi, Jianlin

    2009-09-01

    Hollow mesoporous carbon spheres with magnetic cores are directly replicated from hollow mesoporous aluminosilicate spheres with hematite cores by a simple incipient-wetness impregnation technique. The amount of magnetic cores and the saturation magnetization value can be easily tuned by changing the concentration of iron nitrate solution used in the synthesis procedure. As-prepared hollow mesoporous carbon spheres with magnetic cores are used as separable bilirubin adsorbents and show very good adsorptive properties. The characteristics of as-prepared composites are examined by XRD, N(2) sorption, TEM, vibrating-sample magnetometry, and UV/Vis spectroscopy. PMID:19582733

  11. SCN8A encephalopathy: Research progress and prospects.

    PubMed

    Meisler, Miriam H; Helman, Guy; Hammer, Michael F; Fureman, Brandy E; Gaillard, William D; Goldin, Alan L; Hirose, Shinichi; Ishii, Atsushi; Kroner, Barbara L; Lossin, Christoph; Mefford, Heather C; Parent, Jack M; Patel, Manoj; Schreiber, John; Stewart, Randall; Whittemore, Vicky; Wilcox, Karen; Wagnon, Jacy L; Pearl, Phillip L; Vanderver, Adeline; Scheffer, Ingrid E

    2016-07-01

    On April 21, 2015, the first SCN8A Encephalopathy Research Group convened in Washington, DC, to assess current research into clinical and pathogenic features of the disorder and prepare an agenda for future research collaborations. The group comprised clinical and basic scientists and representatives of patient advocacy groups. SCN8A encephalopathy is a rare disorder caused by de novo missense mutations of the sodium channel gene SCN8A, which encodes the neuronal sodium channel Nav 1.6. Since the initial description in 2012, approximately 140 affected individuals have been reported in publications or by SCN8A family groups. As a result, an understanding of the severe impact of SCN8A mutations is beginning to emerge. Defining a genetic epilepsy syndrome goes beyond identification of molecular etiology. Topics discussed at this meeting included (1) comparison between mutations of SCN8A and the SCN1A mutations in Dravet syndrome, (2) biophysical properties of the Nav 1.6 channel, (3) electrophysiologic effects of patient mutations on channel properties, (4) cell and animal models of SCN8A encephalopathy, (5) drug screening strategies, (6) the phenotypic spectrum of SCN8A encephalopathy, and (7) efforts to develop a bioregistry. A panel discussion of gaps in bioregistry, biobanking, and clinical outcomes data was followed by a planning session for improved integration of clinical and basic science research. Although SCN8A encephalopathy was identified only recently, there has been rapid progress in functional analysis and phenotypic classification. The focus is now shifting from identification of the underlying molecular cause to the development of strategies for drug screening and prioritized patient care. PMID:27270488

  12. Displacement of bilirubin from cord serum by sulphadimethoxine, amoxycillin, clavulanic acid in combination with either amoxycillin or ticarcillin, temocillin and cloxacillin.

    PubMed Central

    Davies, B E

    1985-01-01

    The displacement of bilirubin from its binding sites in cord serum by sulphadimethoxine and various penicillins was studied using Sephadex gel filtration. Sulphadimethoxine displaced bilirubin at concentrations well within the normal therapeutic range of sulphonamide concentrations. Amoxycillin, clavulanic acid in combination with either amoxycillin or ticarcillin, temocillin and cloxacillin displaced bilirubin at concentrations much higher than those found clinically. It was concluded that the primary binding site/s of sulphadimethoxine and the secondary binding site/s of the penicillins were at or near the primary bilirubin binding site. PMID:4074603

  13. Fulminant hepatic failure (FHF) due to acute hepatitis C.

    PubMed

    Younis, Bilal Bin; Arshad, Rozina; Khurhsid, Saima; Masood, Junaid; Nazir, Farhan; Tahira, Maham

    2015-01-01

    Acute hepatitis C (HCV) infection has been identified as an important cause of fulminant hepatic failure (FHF), characterized by rapid deterioration of liver function from massive hepatic necrosis leading to encephalopathy and multi-organ failure. We admitted a female patient at Shalamar Hospital with jaundice, fever, encephalopathy and coagulopathy of short duration with no history of any comorbidity. Her hepatitis viral screen revealed positive anti HCV. Her viral loads were also high. A diagnosis of FHF due to acute HCV infection was made. Patient was treated conservatively and improved gradually. In summary, acute HCV can cause FHF and should be ruled out in patients with FHF of unknown cause in an endemic country for HCV like Pakistan.

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

    PubMed Central

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

    2015-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2014-11-01

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

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

    PubMed

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

    2016-09-01

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

  17. Photo-isomerization and oxidation of bilirubin in mammals is dependent on albumin binding.

    PubMed

    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).

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

    PubMed

    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.

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

    PubMed Central

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

    1998-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  2. Normoammonemic encephalopathy: solely valproate induced or multiple mechanisms?

    PubMed Central

    Budhdeo, Sanjay; Marquette, Malcolm; Singh, Deepwant; Rajagopal, Vivek

    2014-01-01

    A 77-year-old woman presented with subacute onset progressive confusion, aggression, auditory hallucinations and delusions. In the preceding months, the patient had a number of admissions with transient unilateral hemiparesis with facial droop, and had been started on valproate for presumed hemiplegic migraine. Valproate was withdrawn soon after admission and her cognitive abilities have gradually improved over 3 months of follow-up. Valproate levels taken prior to withdrawal were subtherapeutic and the patient was normoammonaemic. EEG undertaken during inpatient stay showed changes consistent with encephalopathy, and low titre N-methyl-d-aspartate (NMDA) receptor antibodies were present in this patient. The possible aetiologies of valproate-induced encephalopathy and NMDA receptor-associated encephalitis present a diagnostic dilemma. We present a putative combinatorial hypothesis to explain this patient's symptoms. PMID:24614773

  3. Pathophysiology of septic encephalopathy--an unsolved puzzle.

    PubMed

    Flierl, Michael A; Rittirsch, Daniel; Huber-Lang, Markus S; Stahel, Philip F

    2010-01-01

    The exact cellular and molecular mechanisms of sepsis-induced encephalopathy remain elusive. The breakdown of the blood-brain barrier (BBB) is considered a focal point in the development of sepsis-induced brain damage. Contributing factors for the compromise of the BBB include cytokines and chemokines, activation of the complement cascade, phagocyte-derived toxic mediators, and bacterial products. To date, we are far from fully understanding the neuropathology that develops as a secondary remote organ injury as a consequence of sepsis. However, recent studies suggest that bacterial proteins may readily cross the functional BBB and trigger an inflammatory response in the subarachnoid space, in absence of a bacterial invasion. A better understanding of the pathophysiological events leading to septic encephalopathy appears crucial to advance the clinical care for this vulnerable patient population.

  4. Severe valproate induced hyperammonemic encephalopathy successfully managed with peritoneal dialysis.

    PubMed

    Kumar, Amandeep; Suri, Ashish; Sharma, Bhawani S

    2014-07-01

    Valproic acid (VPA) is a commonly used drug for epilepsy, psychiatric disorders and migraine and is frequently used in neurosurgical intensive care units. Though most of its side-effects are mild and transient, certain idiosyncratic side-effects have been attributed to VPA. Valproate induced hyperammonemia (VIH) is one such side-effect. VIH can produce symptoms of encephalopathy known as valproate induced hyperammonemic encephalopathy (VHE). VIH and VHE usually respond to withdrawal of VPA. However, in some cases VHE can be unresponsive to supportive measures and severe enough to be life-threatening. In such cases, dialysis can be used to rapidly reverse hyperammonemia and VHE and can prove to be a lifesaving measure. We report such a case of VIH and life-threatening VHE in a postoperative neurosurgical patient that was managed successfully with peritoneal dialysis.

  5. Nutritional support in the treatment of chronic hepatic encephalopathy.

    PubMed

    Milke García, María del Pilar

    2011-06-01

    The prevalence of under nutrition in cirrhotic patients is 61% and it usually progresses as the disease becomes more advanced. The deterioration in the nutritional status and its associated metabolic derangements has raised doubts about the benefits of severe and prolonged protein restriction as a treatment for hepatic encephalopathy. However, the practice of dietary protein restriction for patients with liver cirrhosis is deeply embedded among medical practitioners and dietitians. To date, no solid conclusions may be drawn about the benefit of protein restriction. However, the negative effects of protein restriction are clear, that is, increased protein catabolism, the release of amino acids from the muscle, and possible worsening of hepatic encephalopathy. In conclusion, chronic protein restriction causes progressive and harmful protein depletion and must be avoided. PMID:22228881

  6. [Diabetic encephalopathy: an underexposed complication of diabetes mellitus].

    PubMed

    Brands, A M A; Henselmans, J M L; de Haan, E H F; Biessels, G J

    2003-01-01

    Diabetes mellitus seems to be associated with gradually developing end-organ damage to the central nervous system. This relatively unknown complication of both diabetes type 1 and type 2 can be referred to as 'diabetic encephalopathy'. Measurable manifestations are electrophysiological and structural changes and limitations in the cognitive functioning. The mechanisms responsible for this diabetic encephalopathy are only partially known. Chronic metabolic and vascular changes seem to play an important role. The effects of diabetes on the brain are most distinct in the elderly. This may be the consequence of interactions between the mechanisms that underlie the ageing of the brain, dementia and the origin of diabetic complications. At present there are few leads for the targeted diagnostics and treatment of individual patients.

  7. Hepatic Encephalopathy: From the Pathogenesis to the New Treatments

    PubMed Central

    Cordoba, Juan

    2014-01-01

    Hepatic encephalopathy is a frequent and serious complication of liver cirrhosis; the pathophysiology of this complication is not fully understood although great efforts have been made during the last years. There are few prospective studies on the epidemiology of this complication; however, it is known that it confers with high short-term mortality. Hepatic encephalopathy has been classified into different groups depending on the degree of hepatic dysfunction, the presence of portal-systemic shunts, and the number of episodes. Due to the large clinical spectra of overt EH and the complexity of cirrhotic patients, it is very difficult to perform quality clinical trials for assessing the efficacy of the treatments proposed. The physiopathology, clinical manifestation, and the treatment of HE is a challenge because of the multiple factors that converge and coexist in an episode of overt HE. PMID:27335836

  8. [RENDU-OSLER DISEASE: A RARE CAUSE OF AMMONIA ENCEPHALOPATHY].

    PubMed

    Dumont, R; Loly, J-P; Delwaide, J; Louis, E

    2016-02-01

    Hereditary Hemorrhagic Telangiectasia (HHT) also known as Rendu-Osler disease is a group of related disorders inherited in an autosomal dominant fashion and characterized by the development of arteriovenous malformations (AVM) in the skin, mucous membranes, and/or internal organs such as the brain, lungs, and liver. The prevalence of liver involvement is clinically estimated between 8 and 31 percent. It can be revealed by the following clinical signs : ascites, edema of the lower extremities, abdominal pain, dyspnea, and, rarely, hepatic encephalopathy and gastrointestinal bleeding associated with portal hypertension. This case illustrates the highlight of liver damage revealed by an ammonia encephalopathy associated with iconographic anomalies on ultrasonography and magnetic resonance liver as part of Rendu-Osler disease. PMID:27141651

  9. Laboratory activities involving transmissible spongiform encephalopathy causing agents

    PubMed Central

    Leunda, Amaya; Van Vaerenbergh, Bernadette; Baldo, Aline; Roels, Stefan; Herman, Philippe

    2013-01-01

    Since the appearance in 1986 of epidemic of bovine spongiform encephalopathy (BSE), a new form of neurological disease in cattle which also affected human beings, many diagnostic and research activities have been performed to develop detection and therapeutic tools. A lot of progress was made in better identifying, understanding and controlling the spread of the disease by appropriate monitoring and control programs in European countries. This paper reviews the recent knowledge on pathogenesis, transmission and persistence outside the host of prion, the causative agent of transmissible spongiform encephalopathies (TSE) in mammals with a particular focus on risk (re)assessment and management of biosafety measures to be implemented in diagnostic and research laboratories in Belgium. Also, in response to the need of an increasing number of European diagnostic laboratories stopping TSE diagnosis due to a decreasing number of TSE cases reported in the last years, decontamination procedures and a protocol for decommissioning TSE diagnostic laboratories is proposed. PMID:24055928

  10. Vogt-Koyanagi-Harada syndrome presenting with encephalopathy

    PubMed Central

    Naeini, Alireza E.; Daneshmand, Dana; Khorvash, Farzin; Chitsaz, Ahmad

    2014-01-01

    Vogt-Koyanagi-Harada (VKH) is a rare syndrome affecting tissues containing melanocytes. The possibility of its autoimmune pathogenesis is supported by high frequent HLA-DR4 presentation, commonly associated with other autoimmune diseases. Eyes are the main affected organs, resulting in blindness. Brain disease is a late-onset event, and is extremely rare. Here, we are reporting a 57-year-old woman, a known case of VKH syndrome, presenting with brain encephalopathy several decades after the initial presentation. We think this long period between initial presentation and presentation of encephalopathy due to VKH syndrome has not been described before. She was treated with corticosteroids and discharged home with a good general condition. PMID:24753681

  11. Guest Editorial: Managing Bovine Spongiform Encephalopathy Risk in the United States.

    PubMed

    McCarty, Rick

    2002-01-01

    The United States has built a triple firewall system to prevent the introduction or emergence of bovine spongiform encephalopathy. The firewalls are preventing bovine spongiform encephalopathy's introduction through bans on imports of animals and animal products, actively looking for bovine spongiform encephalopathy in the US cattle herd, and banning ruminant animal feed supplements found to carry the infectious agent and spread the disease in England. PMID:11984425

  12. Epileptic encephalopathies: Optimizing seizure control and developmental outcome.

    PubMed

    Jehi, Lara; Wyllie, Elaine; Devinsky, Orrin

    2015-10-01

    Cognitive and developmental outcomes in patients with epileptic encephalopathy are hypothesized to result from an interplay between the underlying epileptic pathologic substrate and the acquired consequences of frequent and repetitive seizures and epileptiform discharges that often straddle the interictal and ictal boundaries. This article briefly reviews the evidence related to this assumption, presents critical questions that need to be answered to clarify this relationship, and advances a set of concrete steps that may help improve developmental patient outcomes. PMID:26293588

  13. [Transmissible spongiform encephalopathies: neuroinfections with unconventional immune reactions].

    PubMed

    Mitrová, E

    1997-04-01

    Transmissible spongiform encephalopathies (TSE) as well as the properties of the major component of the infectious agent-prion, and the most important human and animal prion diseases are characterized. Considering the recent biochemical and molecular biological data, possible explanations of natural resistance, species barrier and lack of the immune response to the unconventional infectious particles are presented. Finally the importance of immunoblotting and immunostaining as the most specific confirmation of TSE diagnosis is underlined. (Ref. 11.)

  14. Hypothermia for Hypoxic Ischemic Encephalopathy in Infants ≥ 36 weeks

    PubMed Central

    Higgins, Rosemary D.; Shankaran, Seetha

    2009-01-01

    Hypoxic ischemic encephalopathy is a serious condition affecting infants which can result in death and disability. This is a summary of pathogenesis of HIE, animal studies of cooling for hypoxic and ischemic models, human hypothermia trials, and the American Academy of Pediatrics publication on hypothermia for HIE. Hypothermia for neonatal HIE is continuing to evolve as a therapy. Studies, gaps in knowledge and opportunities for research are presented herein. PMID:19762176

  15. Non-typhoidal Salmonella encephalopathy involving lipopolysaccharide in cattle.

    PubMed

    Xiong, N; Brewer, M T; Anderson, K L; Carlson, S A

    2013-02-22

    This study assessed the involvement of lipopolysaccharide (LPS) in the non-typhoidal Salmonella encephalopathy (NTSE) caused by a unique isolate of Salmonella enterica serovar Saint-paul (SstpNPG). NTSE was prevented by genetic (deletion of murE) or pharmacologic (polymyxin) disruption of LPS on SstpNPG although the disruption of LPS did not deter brain penetration of the strain. This is the first study to demonstrate that LPS is involved in the manifestations of NTSE. PMID:22939987

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

    PubMed Central

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

    1995-01-01

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

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

    PubMed Central

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

    2010-01-01

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

  18. Persistent portosystemic shunts after deceased donor liver transplant causing episodic hepatic encephalopathy despite good graft function

    PubMed Central

    Barritt, A. Sidney; Fried, Michael W.; Hayashi, Paul H.

    2011-01-01

    We describe two cases of post liver transplant encephalopathy caused by persistent portosystemic shunts despite good graft function. Such recurrence of encephalopathy due to persistent shunting has not been reported in the deceased donor liver transplant literature. Our patients had episodic hepatic encephalopathy concordant with elevated serum ammonia levels due to well documented persistent portosystemic shunts. In one of our cases, the shunt was obliterated via coil embolization. This patient's encephalopathy resolved completely and has not recurred over seven months of follow up. The second patient has declined an intervention, but has remained symptom free on maintenance lactulose and rifaximin. PMID:19655248

  19. Wernicke's encephalopathy in a patient with masticator and parapharyngeal space abscess: a case report

    PubMed Central

    2016-01-01

    Wernicke's encephalopathy is a fatal neurological disease caused by thiamine deficiency. Many reports indicate that Wernicke's encephalopathy is caused by malnutrition. We report the case of a 79-year-old female patient who had a left masticator space and parapharyngeal space abscess who was diagnosed with Wernicke's encephalopathy. She reported problems while eating due to the presence of the abscess, but the true quantities of food she was ingesting were never assessed. Clinicians have a responsibility to provide adequate nutritional support by ensuring that patients receive adequate nutrition. Clinicians should also keep in mind that Wernicke's encephalopathy may occur in patients who experienced prolonged periods of malnutrition. PMID:27162754

  20. The Treatment of Hepatic Encephalopathy in the Cirrhotic Patient

    PubMed Central

    Sanyal, Arun J.; Mullen, Kevin D.; Bass, Nathan M.

    2010-01-01

    Cirrhosis of the liver is a rising epidemic in the United States, affecting 2 out of every 1,000 adults. It is responsible for the deaths of more than 27,000 people each year. The primary diseases that underlie cirrhosis include viral hepatitis, alcoholic liver disease, and nonalcoholic fatty liver disease. Monitoring the extent of fibrosis and aggressively treating the underlying disease is essential for maintaining quality of life and preventing the complications of cirrhosis. As patients progress toward end-stage liver disease, the most common complications include portal hypertension, the development of esophageal varices, and hepatic encephalopathy. Esophageal varices can lead to hemorrhaging, a dangerous complication that is fatal in 30–50% of patients during the first occurrence. Hepatic encephalopathy is another serious complication of end-stage liver disease, as it significantly reduces patient quality of life and places heavy economic and caregiving burdens upon the patient's family. In this clinical roundtable monograph, the latest advances in the monitoring of liver disease and the management of portal hypertension and hepatic encephalopathy are discussed. PMID:20567582

  1. Dexamethasone therapy for preventing delayed encephalopathy after carbon monoxide poisoning.

    PubMed

    Li, Q; Song, J J; Zhang, H Y; Fu, K; Lan, H B; Deng, Y

    2015-01-01

    We investigated dexamethasone therapy for preventing delayed encephalopathy after carbon monoxide (CO) poisoning. Eighty healthy male rats were exposed to CO and randomly divided into four groups: hyperbaric oxygen treatment (H), treatment (D), combined hyperbaric and dexamethasone treatment (C), and a control (M) group in which the rats inhaled CO to coma in the hyperbaric oxygen chamber, then were removed without further treatment. Twelve rats were put into the hyperbaric oxygen chamber and treated with air for 60 min (N) group. An eight arm maze was used to evaluate cognitive and memory abilities of these mice. Serum myelin basic protein (MBP) levels were evaluated using ELISA, and magnetic resonance imaging was used to observe brain demyelination and morbidity associated with delayed encephalopathy. A sample of the hippocampus from each group was examined by light microscopy. Cognitive and memory functions decreased in the control group M. Three days after CO poisoning, the serum MBP level of each group increased significantly. On Day 10 after CO poisoning, the MBP levels in groups C and D decreased significantly, but returned to normal on Day 18. MBP levels in the M and H groups were elevated at all time points. Brain MRIs showed significant differences among C, D, H and control M groups. Hematoxylin & eosin staining of the hippocampus showed greater damage in the control M and H groups. Early dexamethasone treatment may be useful for preventing delayed encephalopathy after CO poisoning and may reduce serum MBP levels.

  2. [Posterior reversible encephalopathy syndrome of the midbrain and hypothalamus - a case report of uremic encephalopathy presenting with hypersomnia].

    PubMed

    Shiga, Yuji; Kanaya, Yuhei; Kono, Ryuhei; Takeshima, Shinichi; Shimoe, Yutaka; Kuriyama, Masaru

    2016-01-01

    We report the case of a 73-year-old woman presenting with hypersomnia and loss of appetite. She suffered from diabetic nephropathy without receiving dialysis, in addition to hypertension, which was well controlled without marked fluctuation. There were no objective neurological findings. Her laboratory findings showed renal failure with 3.7 mg/dl of serum creatinine and decreased serum sodium and potassium. Brain magnetic resonance imaging (MRI) showed posterior reversible encephalopathy syndrome (PRES) with vasogenic edema, which was distributed in the dorsal midbrain, medial thalamus, and hypothalamus. After we addressed the electrolyte imbalance and dehydration, her symptoms and MRI findings gradually improved, but faint high signals on MRI were still present 3 months later. Orexin in the cerebrospinal fluid was decreased on admission, but improved 6 months later. We diagnosed uremic encephalopathy with atypical form PRES showing functional disturbance of the hypothalamus. PMID:26640128

  3. Hypoglycemic encephalopathy: a case series and literature review on outcome determination.

    PubMed

    Witsch, Jens; Neugebauer, Hermann; Flechsenhar, Julia; Jüttler, Eric

    2012-10-01

    Data on clinical long-term outcome after the acute phase of hypoglycemic encephalopathy (HE) using validated outcome scales is currently unavailable. Here we report the results of a systematic literature search for studies on HE and data on long-term outcome in patients with HE admitted to three Charité hospitals between January 2005 and July 2010. HE was defined as coma/stupor and blood glucose levels <50 mg/dl on admission, persistence of coma/stupor for ≥24 h despite normalization of blood glucose levels, and exclusion of any other cause of coma/stupor. Outcome was assessed using the modified Rankin scale (mRS), Glasgow Outcome Scale (GOS), and Barthel index (BI). Fifteen patients were included, with a mean age of 60 years (range 29-79). Two were lost to follow-up. Of the remaining 13 patients, six had died (46 %). In the seven survivors, the median mRS score was 0 (range 0-5), median GOS score was 5 (range 2-5), and median BI was 100 (range 0-100). MRIs made in the acute phase were available for three patients and revealed no obvious relation between lesion size or pattern and clinical outcome. To our knowledge, this is the first case series using validated clinical scoring systems to determine clinical long-term outcome after HE. The results suggest that mortality is high, but long-term survival with little or no disability is possible and can be observed in the majority of survivors. Risk of death or poor outcome does not seem to be related to MRI features in the acute phase but rather to other presumably medical factors.

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

    PubMed

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

    2016-03-14

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

  5. Serum bilirubin concentration in healthy adult North-Europeans is strictly controlled by the UGT1A1 TA-repeat variants.

    PubMed

    Kringen, Marianne K; Piehler, Armin P; Grimholt, Runa M; Opdal, Mimi S; Haug, Kari Bente F; Urdal, Petter

    2014-01-01

    The major enzyme responsible for the glucuronidation of bilirubin is the uridine 5'-diphosphoglucose glucuronosyltransferase A1 (UGT1A1) enzyme, and genetic variation in the UGT1A1 gene is reported to influence the bilirubin concentration in the blood. In this study, we have investigated which gene-/haplotype variants may be useful for genetic testing of Gilbert's syndrome. Two groups of samples based on serum bilirubin concentrations were obtained from the Nordic Reference Interval Project Bio-bank and Database (NOBIDA): the 150 individuals with the highest bilirubin (>17.5 µmol/L) and the 150 individuals with normal bilirubin concentrations (<17.5 µmol/L). The individuals were examined for the TA6>TA7 variant in the UGT1A1 promoter and 7 tag-SNPs in an extended promoter region of UGT1A1 (haplotype analysis) and in selected SNPs in candidate genes (SLCO1B3, ABCC2 and NUP153). We found significant odds ratios for high bilirubin level for all the selected UGT1A1 variants. However, in stepwise multivariate logistic regression analysis of all genetic variants together with age, sex, country of origin and fasting time, the repeat variants of UGT1A1 TA6>TA7 and SLCO1B3 rs2117032 T>C were the only variants significantly associated with higher bilirubin concentrations. Most individuals with high bilirubin levels were homozygous for the TA7-repeat (74%) while only 3% were homozygous for the TA7-repeat in individuals with normal bilirubin levels. Among individuals heterozygous for the TA7-repeat, a low frequent UGT1A1-diplotype harboring the rs7564935 G-variant was associated with higher bilirubin levels. In conclusion, our results demonstrate that in testing for Gilbert's syndrome, analyzing for the homozygous TA7/TA7-genotype would be appropriate.

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

  9. Comparison of the biliary excretion of the four isomers of bilirubin-IX in Wistar and homozygous Gunn rats.

    PubMed Central

    Blanckaert, N; Heirwegh, K P; Zaman, Z

    1977-01-01

    The biliary excretion of the four isomers of bilirubin-IX was studied in Wistar rats (JJ) and homozygous Gunn rats (jj). Synthetic preparations of 14C-labelled pigments were used. 1. After intravenous administration, the alpha-isomer was rapidly excreted in conjugated form in bile of Wistar rats. In Gunn rats excretion was insignificant. In contrast, both rat species promptly excreted the non-alpha-isomers at rates that were comparable with that found for bilirubin-IXalpha in Wistar rats. 2. In normal rats about 16% of the beta- and delta-isomers and at least 50% of the gamma-isomer were excreted as ester conjugates of the injected parent bile pigments. Conjugation of the beta- and delta-isomers had occurred exclusively at the carboxyl groups of pyrrole ring D and C respectively. For bilirubin-IXgamma no preference for any carboxyl group could be established. 3. In homozygous Gunn rats the non-alpha-isomers were apparently excreted chemically unaltered. This suggests that, as for bilirubin-IXalpha, conjugation of the non-alpha-isomers is also deficient in Gunn rats. PMID:880229

  10. [Postpartal serum bilirubin levels in the newborn after induction of labour with "prostaglandin cap" or oxytocin (author's transl)].

    PubMed

    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.

  11. Experimental interspecies transmission studies of the transmissible spongiform encephalopathies to cattle: comparison to bovine spongiform encephalopathy in cattle.

    PubMed

    Hamir, Amir N; Kehrli, Marcus E; Kunkle, Robert A; Greenlee, Justin J; Nicholson, Eric M; Richt, Jürgen A; Miller, Janice M; Cutlip, Randall C

    2011-05-01

    Prion diseases or transmissible spongiform encephalopathies (TSEs) of animals include scrapie of sheep and goats; transmissible mink encephalopathy (TME); chronic wasting disease (CWD) of deer, elk and moose; and bovine spongiform encephalopathy (BSE) of cattle. The emergence of BSE and its spread to human beings in the form of variant Creutzfeldt-Jakob disease (vCJD) resulted in interest in susceptibility of cattle to CWD, TME and scrapie. Experimental cross-species transmission of TSE agents provides valuable information for potential host ranges of known TSEs. Some interspecies transmission studies have been conducted by inoculating disease-causing prions intracerebrally (IC) rather than orally; the latter is generally effective in intraspecies transmission studies and is considered a natural route by which animals acquire TSEs. The "species barrier" concept for TSEs resulted from unsuccessful interspecies oral transmission attempts. Oral inoculation of prions mimics the natural disease pathogenesis route whereas IC inoculation is rather artificial; however, it is very efficient since it requires smaller dosage of inoculum, and typically results in higher attack rates and reduces incubation time compared to oral transmission. A species resistant to a TSE by IC inoculation would have negligible potential for successful oral transmission. To date, results indicate that cattle are susceptible to IC inoculation of scrapie, TME, and CWD but it is only when inoculated with TME do they develop spongiform lesions or clinical disease similar to BSE. Importantly, cattle are resistant to oral transmission of scrapie or CWD; susceptibility of cattle to oral transmission of TME is not yet determined.

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

    PubMed

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

    2016-06-01

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

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

    PubMed

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

    2016-06-01

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

  14. Walking unsteadily: a case of acute cerebellar ataxia.

    PubMed

    Simonetta, Federico; Christou, Fotini; Vandoni, Riccardo E; Nierle, Thomas

    2013-01-01

    Acute cerebellar ataxia is an infrequent neurological syndrome in adults especially if complicated by additional neurological deficits. We report the case of a 69-year-old woman who presented with sudden onset of left facial droop, dizziness, slurred speech and impaired balance. Her medical history included paroxysmal atrial fibrillation and a sigmoid diverticular abscess treated with ciprofloxacin and metronidazole. Cranial computed tomographic angiography and MRI showed no signs of acute ischaemia or haemorrhage but demonstrated symmetrically distributed lesions in the cerebellar dentate nuclei. A diagnosis of metronidazole-induced encephalopathy was suspected. Metronidazole was stopped and the patient completely recovered. Metronidazole is a commonly prescribed medication. Clinicians should be aware of the clinical and radiological presentation of metronidazole-induced encephalopathy so that this serious but completely reversible condition can be promptly diagnosed. PMID:23283615

  15. Cystitis - acute

    MedlinePlus

    Uncomplicated urinary tract infection; UTI - acute; Acute bladder infection; Acute bacterial cystitis ... International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: A 2010 ...

  16. Calcineurin Inhibitors Associated Posterior Reversible Encephalopathy Syndrome in Solid Organ Transplantation: Report of 2 Cases and Literature Review.

    PubMed

    Song, Turun; Rao, Zhengsheng; Tan, Qiling; Qiu, Yang; Liu, Jinpeng; Huang, Zhongli; Wang, Xianding; Lin, Tao

    2016-04-01

    Posterior reversible encephalopathy syndrome (PRES) is a rare neurologic side effect of calcineurin inhibitors (CNIs) with poorly understood clinical features.We report cases of 2 patients with PRES developing after kidney transplantation and summarize PRES clinical features through a literature review.The 1st case was a 28-year-old man who received a kidney transplant from a deceased donor. Initial immunosuppressive therapy consisted of tacrolimus/mycophenolate mofetil/prednisolone. He developed headache and blurred vision with visual field loss15 days after transplantation and generalized seizures 4 days later. The 2nd case was a 34-year-old man who received a living kidney transplant. His initial immunosuppressive therapy comprised tacrolimus/mycophenolate mofetil/prednisolone. Two months after transplantation, he developed seizures. Both patients were diagnosed with PRES based on neurological symptoms and magnetic resonance imaging (MRI) findings; they recovered after switching from tacrolimus to either a cyclosporine or a lower tacrolimus dose. CNI-associated PRES is an acute neurological syndrome with seizures, encephalopathy, visual abnormalities, headache, focal neurological deficits, and nausea/vomiting. It is always accompanied by hypertension. A fluid-attenuated inversion recovery signal MRI scan typically shows reversible subcortical white matter changes in the posterior cerebral hemisphere that usually occur within the 1st month after transplantation. CNI-associated PRES has a generally favorable prognosis with early diagnosis and prompt treatment including alternating or discontinuing CNIs and blood pressure control.CNI-associated PRES should be considered in patients exhibiting acute neurological symptoms after transplantation. Early diagnosis and immediate treatment are critical for a favorable prognosis. PMID:27057842

  17. Localized Cerebral Energy Failure in DNA Polymerase Gamma-Associated Encephalopathy Syndromes

    ERIC Educational Resources Information Center

    Tzoulis, Charalampos; Neckelmann, Gesche; Mork, Sverre J.; Engelsen, Bernt E.; Viscomi, Carlo; Moen, Gunnar; Ersland, Lars; Zeviani, Massimo; Bindoff, Laurence A.

    2010-01-01

    Mutations in the catalytic subunit of the mitochondrial DNA-polymerase gamma cause a wide spectrum of clinical disease ranging from infantile hepato-encephalopathy to juvenile/adult-onset spinocerebellar ataxia and late onset progressive external ophthalmoplegia. Several of these syndromes are associated with an encephalopathy that…

  18. Stability properties of PrPSc from cattle with experimental transmissible spongiform encephalopathies

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Transmissible Spongiform Encephalopathies (TSEs), including scrapie in sheep, chronic wasting disease (CWD) in cervids, and bovine spongiform encephalopathy (BSE), are fatal diseases of the nervous system associated with accumulation of misfolded prion protein (PrPSc). Different strains of BSE exist...

  19. Experimental Inoculation of Spiroplasma mirum and Transmissible Mink Encephalopathy (TME) into Raccoons (Procyon lotor)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To determine if Spiroplasma mirum would be capable of producing lesions of spongiform encephalopathy in raccoons (Procyon lotor), 5 groups (n = 5) of raccoon kits were inoculated intracerebrally with either S. mirum and/or transmissible mink encephalopathy (TME). Two other groups (n = 5) of raccoon...

  20. Coupled plasma filtration adsorption reduces serum bilirubine in a case of acute hypoxic hepatitis secondary to cardiogenic shock.

    PubMed

    Caroleo, Santo; Rubino, Antonino S; Tropea, Francesco; Bruno, Orlando; Vuoto, Domenico; Amantea, Bruno; Renzulli, Attilio

    2010-10-01

    Hypoxic hepatitis (HH) is a severe complication of postoperative low output syndrome, associated with high mortality rates despite appropriate drug therapy. Recently several extracorporeal supportive techniques have become available. We describe the case of a 70-year-old woman who developed HH secondary to cardiogenic shock after cardiac surgery. CPFA proved to be a valid tool for concomitant hemodynamic support and organ replacement therapy.