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

PENGARUH PEMBERIAN SUPLEMENTASI SUPEROXIDE DISMUTASE (SOD) TERHADAP KADAR ALBUMIN SERUM PADA LANSIA

Background: Levels of serum albumin can be used as a predictor of morbidity and mortality in the elderly. Reduced serum albumin concentration can be caused by oxidative modification due to aging or insufficient protein intake. SOD as an enzymatic antioxidant might prevent oxidative stress so that albumin modification process can be inhibited. SOD supplementation was expected to increase serum albumin levels. Aim: Analyze the effect of SOD supplementation on elderly serum albumin level. Methods: This was a true experimental study with pre and post test control group design.. The study began with 31 elderly, resides in the “Pucang Gading Social Rehabilitation Unit”. They were divided into 2 groups. The control group (15 subjects), received placebo and exercise. The treatment group (16 subjects), received 250 IU SOD/day and exercise. Both treatments were done within 8 weeks, with twice a week exercise. Before and after treatment, levels of serum albumin were measured. Data normality was tested using Saphiro-wilk test. Data was analyzed by Paired-T-test if the distribution is normal, and using Wilcoxon test if the distribution is abnormal. Results: There were increases of serum albumin levels in both groups. Statistical test results showed a significant increase of serum albumin levels in the treatment group of 0.26 ± 0.33 mg/dL with p=0,007 (p0,05). Conclusion: 250 IU SOD/day supplementation for 8 weeks increase serum albumin levels in the elderly. Keywords: Albumin, elderly, aging, SO

State of Harmonization of 24 Serum Albumin Measurement Procedures and Implications for Medical Decisions

BACKGROUND: Measurements of serum and plasma albumin are widely used in medicine, including as indicators of quality of patient care in renal dialysis centers. METHODS: Pools were prepared from residual patient serum (n = 50) and heparin plasma (n = 48) from patients without renal disease, and serum from patients with kidney failure before hemodialysis (n = 53). Albumin was measured in all samples and in ERM-DA470k/IFCC reference material (RM) by 3 immunochemical, 9 bromcresol green (BCG), and 12 bromcresol purple (BCP) methods. RESULTS: Two of 3 immunochemical procedures, 5 of 9 BCG, and 10 of 12 BCP methods recovered the RM value within its uncertainty. One immunochemical and 3 BCG methods were biased vs the RM value. Random error components were small for all measurement procedures. The Tina-quant immunochemical method was chosen as the reference measurement procedure based on recovery and results of error analyses. Mean biases for BCG vs Tina-quant were 1.5% to 13.9% and were larger at lower albumin concentrations. BCP methods\u27 mean biases were -5.4% to 1.2% irrespective of albumin concentration. Biases for plasma samples were generally higher than for serum samples for all method types. For most measurement procedures, biases were lower for serum from patients on hemodialysis vs patients without kidney disease. CONCLUSIONS: Significant differences among immunochemical, BCG, and BCP methods compromise interpretation of serum. albumin results. Guidelines and calculations for clinical management of kidney and other diseases must consider the method used for albumin measurement until harmonization can be achieved

Binding of bromocresol green and bromocresol purple to albumin in hemodialysis patients

BACKGROUND: Colorimetric albumin assays based on binding to bromocresol purple (BCP) and bromocresol green (BCG) yield different results in chronic kidney disease. Altered dye binding of carbamylated albumin has been suggested as a cause. In the present study, a detailed analysis was carried out in which uremic toxins, acute phase proteins and Kt/V, a parameter describing hemodialysis efficiency, were compared with colorimetrically assayed (BCP and BCG) serum albumin. METHODS: Albumin was assayed using immunonephelometry on a BN II nephelometer and colorimetrically based on, respectively, BCP and BCG on a Modular P analyzer. Uremic toxins were assessed using high-performance liquid chromatography. Acute phase proteins (C-reactive protein and α1-acid glycoprotein) and plasma protein α2-macroglobulin were assayed nephelometrically. In parallel, Kt/V was calculated. RESULTS: Sixty-two serum specimens originating from hemodialysis patients were analyzed. Among the uremic toxins investigated, total para-cresyl sulfate (PCS) showed a significant positive correlation with the BCP/BCG ratio. The serum α1-acid glycoprotein concentration correlated negatively with the BCP/BCG ratio. The BCP/BCG ratio showed also a negative correlation with Kt/V. CONCLUSIONS: In renal insufficiency, the BCP/BCG ratio of serum albumin is affected by multiple factors: next to carbamylation, uremic toxins (total PCS) and α1-acid glycoprotein also play a role

Sequence homology between RNAs encoding rat α-fetoprotein and rat serum albumin

We have determined the sequences of the recombinant DNA inserts of three bacterial plasmid cDNA clones containing most of the rat α-fetoprotein mRNA. The resultant nucleotide sequence of α-fetoprotein was exhaustively compared to the nucleotide sequence of the mRNA encoding rat serum albumin. These two mRNAs have extensive homology (50%) throughout and the same intron locations. The amino acid sequence of rat α-fetoprotein has been deduced from the nucleotide sequence, and its comparison to rat serum albumin's amino acid sequence reveals a 34% homology. The regularly spaced positions of the cysteines found in serum albumin are conserved in rat α-fetoprotein, indicating that these two proteins may have a similar secondary folding structure. These homologies indicate that α-fetoprotein and serum albumin were derived by duplication of a common ancestral gene and constitute a gene family

Long-Range Proton Conduction Across Free-Standing Serum Albumin

Free‐standing serum‐albumin mats can transport protons over millimetre length‐scales. The results of photoinduced proton transfer and voltage‐driven proton‐conductivity measurements, together with temperature‐dependent and isotope‐effect studies, suggest that oxo‐amino‐acids of the protein serum albumin play a major role in the translocation of protons via an “over‐the‐barrier” hopping mechanism. The use of proton‐conducting protein mats opens new possibilities for bioelectronic interfaces

Binding of Oxovanadium(IV) Complexes to Blood Serum Albumins

In this work the binding of VIVO2+ and VIVO-complexes to serum albumins {human serum albumin (HSA), bovine serum albumin (BSA) and porcine serum albumin (PSA)} are studied using circular dichroism (CD), electron paramagnetic resonance (EPR) and visible absorption spectroscopy. The results confirm previous findings that VIVO2+ occupies at least two types of binding sites on albumin: ‘the strong vanadium binding site’ (designated by VBS1) and ‘the weak vanadium binding sites’ (designated by VBS2). VBS1 binds 1 mol equivalent of VIVO2+. On the other hand VBS2 correspond to binding of several mol equivalents of VIVO, and studies done with PSA in the presence of excess ZnII ions indicate that VSB2 corresponds to two distinct types of sites. The hyperfine coupling constant Az for VIVO2+ binding at VBS2 on HSA and BSA are all very similar (~168 × 10-4 cm-1) but differ slightly on PSA (~166 × 10-4 cm-1) due to differences in the binding sets. When (VIVO)-HSA systems are titrated with maltol ternary species of (maltol)m(VIVO)mHSA and (maltol)2m(VIVO)mHSA stoichiometry form which are clearly distinguishable from the binary (VIVO)-HSA system by the type and intensity of the CD spectra recorded. Changes are also observable in the intensity of the X-band EPR spectra, but not much in the hyperfine coupling constants Az, which are all in the range 166-167 × 10-4 cm-1. The results further demonstrate that the presence of maltol may enhance the binding of VIVO to albumin

Correlation Between Serum Albumin Level and Degree of Esophageal Varices in Patients with Liver Cirrhosis

Background: It has not been clear about how often the patient should have esophago- gastroduodenoscopy (EGD) screening for esophageal varices (EV) detection and there is only some data that demonstrates the correlation between the degree of EV and non-endoscopic variables. It is assumed that the presence of EV detected though examination of serum albumin level may trim down the unnecessary endoscopy. This study was aimed to recognize the correlation between albumin level and the degree of EV in patients with liver cirrhosis. Method: A retrospective analysis was performed for 61 patients with liver cirrhosis who had EGD at Sanglah hospital between January and December 2008. Spearman test was used to analyze the correlation between albumin level and the degree of EV. Results: There were 61 patients of 45 (73.8%) male and 16 (26.2%) female. The range age of patients was 13–77 years (average 49.98 ± 1.62 years). Serum albumin level ranged between 1.10-3.60 mg/dL, the average value was 2.21 ± 0.451 mg/dL. We also found 8 (13.1%) patients without EV, 14 (23.0%) patients with EV grade I, 21 (34.4%) patients with grade II and 18 (29.5%) patients with grade III. A negative correlation was found between serum albumin level and the degree of EV (r = - 0.587; p = 0.000, p < 0.01). Conclusion: Serum albumin level can predict the presence and the degree of EV in patients with liver cirrhosis

Cryopreservation protocol for human biliary tree stem/progenitors, hepatic and pancreatic precursors

Human biliary tree stem/progenitor cells (hBTSCs) are being used for cell therapies of patients with liver cirrhosis. A cryopreservation method was established to optimize sourcing of hBTSCs for these clinical programs and that comprises serum-free Kubota's Medium (KM) supplemented with 10% dimethyl sulfoxide (DMSO), 15% human serum albumin (HSA) and 0.1% hyaluronans. Cryopreserved versus freshly isolated hBTSCs were similar in vitro with respect to self-replication, stemness traits, and multipotency. They were able to differentiate to functional hepatocytes,cholangiocytes or pancreatic islets, yielding similar levels of secretion of albumin or of glucose-inducible levels of insulin. Cryopreserved versus freshly isolated hBTSCs were equally able to engraft into immunocompromised mice yielding cells with human-specific gene expression and human albumin levels in murine serum that were higher for cryopreserved than for freshly isolated hBTSCs. The successful cryopreservation of hBTSCs facilitates establishment of hBTSCs cell banking offering logistical advantages for clinical programs for treatment of liver diseases