Ursodeoxycholic acid improves bilirubin but not albumin in primary biliary cirrhosis: further evidence for nonefficacy.

BACKGROUND/AIM: In randomised controlled trials (RCTs) of ursodeoxycholic acid (UDCA), although serum bilirubin is frequently reduced, its effect on disease progression and mortality is unclear. As serum albumin is an established independent prognostic marker, one might expect less deterioration of serum albumin values in a UDCA-treated group. We therefore modelled the typical evolution of serum bilirubin and albumin levels over time in UDCA-untreated patients and compared it with the observed levels in UDCA RCTs. METHODS: Multilevel modelling was used to relate the evolution of serum albumin to serum bilirubin and time since patient referral. For each considered RCT, the derived model was used to predict the relationship between final mean serum albumin and bilirubin concentration, adjusted for mean serum albumin at referral and followup duration. RESULTS: Five RCTs were eligible in terms of available data, of which two had long followup. In all trials, serum albumin did not significantly differ between UDCA- and placebo-treated patients, despite the UDCA effect on serum bilirubin. Therefore, there is no evidence over time for changes or maintenance of albumin levels for UDCA-treated patients above the levels predicted for placebo-treated patients. CONCLUSIONS: Our findings suggest that UDCA does not alter serum albumin in a way that is consistent with its effect on serum bilirubin. Therefore, reductions in serum bilirubin of UDCA-treated PBC do not parallel another validated and independent prognostic marker, further questioning the validity of serum bilirubin reduction with UDCA as a surrogate therapeutic marker

Studies on Bile Pigments II. Seperation of Natural Direct Bilirubins

Separation of both forms of the direct bilirubin were carried out from the dog's gallbladder bile, and further isolations of them were also done. 1. The natural salt-form bilirubin was isolated after separation on the column of aluminium oxide with a n-propanolic aqueous solution. 2. The natural salt-form bilirubin was obtained in amorphous yellow powders which were strongly hygroscopic and easily soluble in water and methanol but not in chloroform or carbon tetrachloride. An aqueous solution of these powders showed both the direct diazo and Gmelin reaction, but neither Ehrlich's aldehyde nor Schlesinger reaction. The salt-form bilirubin was transferred into chloroform only when some quantities of hydrochloric acid were added to a mixture of chloroform and an aqueous solution of it. 3. The absorption maxima of the natural salt-form bilirubin existed at 420 to 430 m&#956; in a methanolic solution and at 425 or 435m&#956; in 50% or 10% n-propanol. 4. The natural ester-form bilirubin was isolated after separating on the column of silica gel with a chloroformethanolic mixture. 5. The natural ester-form bilirubin was obtained in amorphous greenish yellow powders. It was further hygroscopic and easily soluble in water and methanol but not in chloroform or carbon tetrachloride. An aqueous solution of it showed the direct diazo and Gmelin reaction, but neither Ehrlich's aldehyde nor Schlesinger's reaction. No pigment was transferred into chloroform even if some quantities of hydrochloric acid were added to a mixture of chloroform and an aqueous solution of it, but did by saponification with 5% methanolic potash. 6. The absorption maxima of the natural ester-form bilirubin existed at 415 m&#956; in both methanolic and aqueous solutions.</p

Transcutaneous Bilirubinometry in a Rural Teaching Hospital: A Quality Improvement Assessment

Purpose: Up to 84% of term neonates develop jaundice, a sign of hyperbilirubinemia that warrants bilirubin measurement. The AAP recommends systematic evaluation of hyperbilirubinemia risk for every infant. Serum bilirubin tests involve needle sticks, introducing anxiety, pain, and cost. Transcutaneous bilirubin (TcB) measures bilirubin without needle sticks, may offer reduced costs, but is less accurate, and may increase phototherapy rates. This determined the effect of TcB measurement on needle sticks, phototherapy rates, and cost of bilirubin measurement at a rural teaching hospital. Methods: A retrospective data analysis compared rates of bilirubin screening, needle stick testing, and phototherapy treatment for a three-month period prior to the introduction of TcB measurement with a three-month period following introduction. Rate differences were calculated with SPSS statistical package. A comparison of error test determined statistical significance. The institution’s billing and purchasing department provided cost data. Results: The introduction of TcB measurement increased hyperbilirubinemia screening from 21.1% to 83%, which was statistically significant. Needle stick testing decreased to a degree that was clinically but not statistically significant. Phototherapy treatment increased but was not statistically significant. The charge was $33.00 less per incidence than needle stick testing. Conclusions: This quality improvement assessment demonstrates that TcB screening increases systematic assessment for hyperbilirubinemia, thereby increasing adherence to AAP recommendations. This assessment highlights the need for formal studies to investigate an appropriate TcB threshold for needle stick testing, as well as the effect of such a threshold on needle stick testing to inform best practice

The effects of Bilirubin and Bilirubin-di-taurate on ischemia reperfusion injruy in a rat model of kidney transplantation

Background: Heme oxygenase-1 (HO-1) is the rate-limiting enzyme in the conversion of heme into biliverdin, carbon monoxide (CO) and free iron. Biliverdin is then subsequently reduced to bilirubin by the enzyme bilverdin reductase. In the past decades a lot of effort was conducted to investigate the beneficial effects of HO-1 and its end products biliverdin/bilirubin and CO. Due to intensive research, solid organ transplantation can nowadays be seen as clinical routine. However ischemia reperfusion injury (IR), acute rejection episodes and the occurrence of chronic rejection remain main problems. The severity of IRI can be seen as a prognostic factor for early graft function, immunogenecity of grafts as well as for long term graft survival. The goal of our experiments was to investigate the potential beneficial effects of bilirubin and biliverdin on ischemia reperfusion in a kidney transplantation model of the rat. Methods: Two different sets of experiments were performed: First, kidneys of Lewis rats were exposed to 60 minutes of warm ischemia by clamping the renal artery followed by a 24h reperfusion period. This model was used to find the optimal dosing regimen of bilirubin/biliverdin before the more clinical relevant model of kidney transplantation in the rat was performed. We found that three doses of 10mg/Kg bilirubin were the most effective dose regimen to protect kidneys from ischemia reperfusion injury. In the second set of experiments, kidney transplantation was performed in Lewis rats. Kidneys were harvested and stored in 4C cold UW-solution for 18h. Subsequently the kidneys were transplanted isotopically into the recipient rat. Time of warm ischemia was kept in all experiments constantly at 60 minutes. After 24h of reperfusion tissue samples and serum were harvested for further analyses. Results: Systemic treatment of bilirubin led to a significant amelioration of organ function after ischemia reperfusion injury as assessed by measuring serum creatinine levels and BUN levels after 24h of reperfusion. In addition treated animals showed increased eGFR and a better cell integrity as histomorphological analyses could demonstrate. Conclusion: Systemic treatment with bilirubin and bilverdin has beneficial effects on graft function after ischemia rerperfusion injury

Adaptive response of neonatal sepsis-derived Group B Streptococcus to bilirubin

This work was funded by the Neonatal Unit Endowment Fund, Aberdeen Maternity Hospital. RH is funded by a career researcher fellowship from NHS Research Scotland. SG was funded by the MRC Flagship PhD programme. We are grateful for the support of Dr Phil Cash and Aberdeen Proteomics, at University of Aberdeen, in completing this project. Supplementary information accompanies this paper at https://doi.org/10.1038/s41598-018-24811-3.Peer reviewedPublisher PD

Bilirubin oxidase from myrothecium verrucaria physically absorbed on graphite electrodes. Insights into the alternative resting from and the sources of activity loss

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

RISIKO GANGGUAN PENDENGARAN PADA NEONATUS HIPERBILIRUBINEMIA

ABSTRACT Background. The prevalence of hearing impairment on the Indonesian population according to 2007 WHO data is estimated at 4.2 %, and one of the cause is neonatal hyperbilirubinemia. Early detection of hearing impairment and optimal intervention on the first 6 months can prevent speech and language impairment, lack of academic achievement, disturbance of personal social relationship and emotional in the children. Method. A Cohort research was conducted in 36 neonates in Dr Kariadi Hospital in March 2009-March 2010, 18 in the case group with indirect bilirubin > 12 mg/dl and 18 neonates as control group with indirect bilirubin < 12 mg/dl, both taken with consecutive sampling method. We recorded clinical, laboratory, and tymphanometry data, OAE and BERA results at first and after three months. Statistical analysis were done using Chi-square analysis, Mc Nemar analysis, and T-test. Results. Hearing impairment on the first BERA examination was 9 cases (25%) and 3 cases (8.3%) on the second BERA examination, however it did not differed significantly (p>0,05). On the first BERA examination, the mean indirect bilirubin concentration with hearing impairment of 14,18+6,289 mg/dl was not significantly different (p>0,05) from neonate without hearing impairment of 11,29+2,995 mg/dl. The Relative Risk (RR) was 2 (p>0,05; 95% CI 0,6-6,8), but statistically it was not significant. Conclusion. The incidence of hearing impairment on neonatal with hyperbilirubinemia is 25%. Indirect bilirubin of > 12 mg/dL is not proved to be the risk factor of hearing impairment in neonatal with hyperbilirubinemia. Keywords:BERA, hearing impairment, neonatal hyperbilirubinemia, OAE

Spectrophotometry for cerebrospinal fluid pigment analysis

The use of spectrophotometry for the analysis of the cerebrospinal fluid (CSF) is reviewed. The clinically relevant CSF pigments--oxyhemoglobin and bilirubin--are introduced and discussed with regard to clinical differential diagnosis and potentially confounding variables (the four T's: traumatic tap, timing, total protein, and total bilirubin). The practical laboratory aspects of spectrophotometry and automated techniques are presented in the context of analytical and clinical specificity and sensitivity. The perceptual limitations of human color vision are highlighted and the use of visual assessment of the CSF is discouraged in light of recent evidence from a national audit in the United Kingdom. Finally, future perspectives including the need for longitudinal CSF profiling and routine spectrophotometric calibration are outlined

STUDIES ON PLANT BILE PIGMENTS

The reaction of bilirubins with aromatic diazonium salts in alcoholic solvents leads to an equimolar mixture of two types of products. One is the well-known 9-azopyrromethenone. The other is a yellow product (A,,, z 420nm) identified as 9-alkoxymethylpyrromethenone. the alkoxy-substituent being derived from the solvent. Thus, reaction of the symmetrically substituted bilirubins llla (lc) and XIIIJ (lb) in methanol with diazotized sulfanilic acid yields one mole of the azopigments (4b and 4a). respectively, and one mole of the corresponding 9-methoxymethylpyrromethcnones (2b and 2a). Bilirubin IXa (la) consequently yields a mixture of all four products. The two resulting 9-methoxymethylpyrromethenoncs were separated by chromatography and identified as 2a and 2b. They can react further with the dia7onium salts lo give the corresponding 9-aznpyrromethenones, but the reaction is much slower than that of bilirubin. which explains the observed product distribution. These results are discussed in relation to earlier work. ALMOST a hundred years ag