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Albumin mRNA in peripheral white blood cells of cirrhotic patients with a superimposed alcoholic hepatitis is associated to fatal outcome.

The aim of this study was to analyze the relationship of plasma colloid osmotic pressure (COP), relative viscosity (eta) and overall outcome on the expression of albumin (ALB) mRNA in peripheral white blood cells (PWBC) of cirrhotic patients with superimposed alcoholic hepatitis (LC+AH). ALB messanger was detected in PWBC by RT-nPCR in control individuals (C), patients with liver cirrhosis (LC) and LC+AH. A higher number of LC+AH patients were positive to ALB mRNA (67%), compared to C (30%) and LC (28%). COP was decreased in LC and LC+AH groups compared to C group. No statistically significant changes were detected in eta in the different populations studied. Most of the LC+AH patients positive to peripheral ALB expression (87%) had a fatal outcome, compared to survivors (25%). Such difference was not observed with the conventional liver function tests or Maddrey's discriminant function.

Journal Article↗

Sandwich ELISAs for quantification of Xenopus laevis vitellogenin and albumin and their application to measurement of estradiol-17 beta effects on whole animals and primary-cultured hepatocytes.

Sandwich enzyme-linked immunosorbent assay (ELISA) was developed for quantification of vitellogenin (VTG) and albumin (ALB) in Xenopus laevis. Working ranges of the ELISAs were 2-1000 ng/ml for VTG and 1-300 ng/ml for ALB. Recoveries of plasma VTG by ELISA were over 90% in dilutions of more than 200 times. The VTG-inducing activity of estradiol-17beta (E2) was measured in whole animals and primary cultured hepatocytes. Immersion of mature male animals in more than 1 nM E2 induced a detectable amount of plasma VTG. VTG induction in younger animals was less potent than in the mature animals but the youngest animals (1.5-3 g body mass) was applicable to the exposure test, irrespective of sex. In vitro exposure of hepatocytes to more than 0.1 nM E2 dose-dependently induced secretion of VTG into the culture medium, while ALB secretion was not significantly affected by E2 treatment. When the VTG-induction levels were normalized by use of a concentration ratio of VTG to ALB, the values obtained from three independent experiments were mutually comparable irrespective of differences in cell density and hepatocyte preparation. Thus, this ratio is thought to be useful for large-scale in vitro screening of estrogenic activities of chemical substances.

Albumins↗

Beer consumption and changes in stability of human serum proteins.

The aim of this study was to evaluate the influence of beer consumption (BC) on the functional and structural properties of human serum proteins (HSP). Thirty-eight volunteers (after coronary bypass) were divided into two groups: experimental (EG) and control (CG). Nineteen volunteers of the EG consumed 330 mL per day of beer (about 20 g of alcohol) for 30 consecutive days. The CG volunteers consumed mineral water instead of beer. Blood samples were collected from EG and CG patients before and after the experiment. Albumin (Alb), globulin (Glo), and methanol-precipitable proteins (MPP) from human serum were denatured with 8 M urea. Fluorescence and electrophoresis were employed in order to elucidate urea-induced conformational changes and structural behavior of proteins. The measured fluorescence emission spectra were used to estimate the stability of native and denatured protein fractions before and after BC. It was found that before BC the fractions most stable to urea denaturation were Glo, Alb, and MPP fractions. After BC in most of the beer-consuming patients (EG) some changes in native and denatured protein fractions were detected: a tendency to lower stability and minor structural deviations. These qualitative changes were more profound in MPP than in Alb and Glo. Thus, Glo is more resistible to alcohol influence than Alb, which in turn is more resistible than MPP. No serum protein changes were detected in patients of CG.

Beer↗

Immobilization of heterobimetallic multifunctional asymmetric catalyst

Immobilization of an asymmetric AlLibis(binaphthoxide) catalyst (ALB) is described. The immobilized ALBs (poly-ALBs) are readily prepared from polymeric BINOL derivatives and LiAlH(4). The combined use of 9 mol % of BuLi with ca. 10 mol % (as a monomeric catalyst) of 6,6'-aryl-tethered poly-ALB gave the Michael adducts with up to 93% ee. After completion of the reaction, the insoluble catalyst was recovered in air and is reusable.

Journal Article↗

Response of Corriedale and Crioula Lanada sheep to artificial primary infection with Haemonchus contortus.

Clinical, parasitological and biochemical parameters were evaluated in Corriedale and Crioula Lanada sheep after a single experimental infection with Haemonchus contortus. Ten 4-month-old worm-free lambs, of each breed, were infected with 200 L3 H. contortus per kg live weight and four uninfected animals of each breed were used as controls. Every week, the animals were weighed and blood and faecal samples were collected for measurement of packed cell volume (PCV), total serum protein (TSP) and albumin (ALB), and the number of eggs per gram of faeces (EPG), respectively. Twelve weeks after infection, the animals were slaughtered. The worm burden was determined and samples of the abomasal mucosa were processed for determination of the number of eosinophils, mast cells and globule leukocytes. No significant differences in PCV, TSP, ALB, parasite burden or the cell populations of the abomasal mucosa were observed between breeds, but Crioula lambs had a lower EPG count. The comparison of the infected groups with their respective controls revealed significant alterations in PCV, TSP and ALB in the Corriedale lambs and in PCV, TSP, ALB and the density of eosinophils and mast cells in the Crioula lambs.

Animals↗

Randomized trial of normal saline versus 5% albumin for the treatment of neonatal hypotension.

OBJECTIVES: This study was designed to assess the comparative efficacy of normal saline (NS) and 5% albumin (ALB) for treatment of hypotension in the acutely ill newborn. STUDY DESIGN: Newborn infants who were < 24 hours old and were admitted to the Holden Neonatal Intensive Care Unit at the University of Michigan were randomized to receive one of the two solutions for volume expansion. Hypotension was defined as a sustained (> or =30 minutes) mean arterial pressure (MAP) of < 30 mmHg for infants weighing < or =2500 g, or a MAP of < 40 mmHg for those weighing > 2500 g. The short-term outcome measure was the resolution of hypotension defined as a MAP over the minimum limits set for birthweight sustained for > or =30 minutes. RESULTS: In total 41 infants met criteria and were entered. Of these, 21 infants received ALB and 20 received NS. Successful treatment was seen in 17/21 (81%) of infants in the ALB group and 17/20 (85%) of infants in the NS group. There was no statistically significant difference in response to treatment (p=0.30). In addition, there was no statistically significant difference in the magnitude of change in MAP between the two (p=0.41). CONCLUSIONS: NS was shown to be as effective as ALB for the correction of acute hypotension in the newborn infant. Given comparable efficacy of NS, along with its relatively low cost and availability, it should be considered the initial treatment of choice in this setting.

Albumins↗

The ALIAS (ALbumin In Acute Stroke) Phase III randomized multicentre clinical trial: design and progress report.

High-dose human ALB (albumin) therapy is highly neuroprotective in animal models of ischaemic stroke. A recently completed 82-subject pilot-phase dose-escalation trial has shown that ALB is safe, with strong preliminary suggestions of possible efficacy. We are now proceeding to a large randomized, double-blinded, placebo-controlled multicentre trial funded by the NIH (National Institutes of Health), the ALIAS (Albumin In Acute Stroke) Phase III Trial, which is designed to ascertain definitively whether high-dose ALB therapy confers neuroprotection in subjects with acute ischaemic stroke treated within 5 h of stroke onset. The primary efficacy outcome measure is a favourable outcome, defined as an NIHSS (NIH Stroke Scale) score of 0-1 or a modified Rankin Scale score of 0-1 at 3 months post-randomization. Separate randomization (1:1) to ALB or placebo therapy will be carried out in two cohorts of 900 subjects each, one that receives standard-of-care thrombolytic therapy and the other that does not. Approx. 60 North American clinical sites will participate. Subject enrollment is expected to commence in July 2006.

Humans↗

Peri-operative tolerance to large-dose 6% HES 200/0.5 in major urological procedures compared with 5% human albumin.

We studied the long-term efficacy and safety of medium-molecular-weight hydroxyethyl starch (HES) administered in doses above 20 ml.kg-1 during major blood replacement therapy. Blood replacement for 50 patients used 6% HES 200/0.5 (HES group) or 5% albumin (ALB group) and additional blood components according to a defined protocol. We compared safety, efficacy and costs in 4 peri-operative days. Colloid administration on the day of surgery was 38.4 ml.kg-1 (HES group) and 35.1 ml.kg-1 (ALB group). Haemodynamic, coagulation and renal function parameters were similar. Although total serum protein was still different on the third postoperative day (53.45 gl-1 (HES group) and 60.6 gl-1 (ALB group) (p < 0.01)) the colloid osmotic pressure always remained above 19.5 (2.5) mmHg (HES group). Blood loss (3810 (1632) ml (HES group) and 3455 (1733) ml (ALB group)) and the requirement for blood components was comparable. Costs were reduced by 35% (p < 0.05) in the HES group. We conclude that using 6% HES 200/0.5 as the only colloid for treatment even of large blood loss is a safe and economic alternative to albumin.

Adult↗

Plasmapheresis in the treatment of steroid-resistant focal segmental glomerulosclerosis in native kidneys.

A circulating glomerular capillary albumin permeability factor (P(alb)) has been implicated in the pathogenesis of focal segmental glomerulosclerosis (FSGS), which recurs in transplanted kidneys. Plasmapheresis for recurrent FSGS may reduce proteinuria and stabilize renal function if instituted early. We performed six plasmapheresis treatments over 2 weeks in eight patients with a history of steroid-resistant idiopathic FSGS in native kidneys for an average of 12 +/- 2.3 months to determine whether treatment would decrease proteinuria or stabilize renal function. P(alb) was measured before and after plasmapheresis, and patients were followed-up for a mean of 29 +/- 4 months after the development of clinical symptoms. Proteinuria decreased in two of eight treated patients, although only transiently in one of the two. P(alb) improved in one of the two responding patients. Both patients with an improvement in proteinuria had stable renal function at last follow-up. In six of eight patients, there was no improvement in proteinuria despite an improvement in P(alb) (P < 0.0001) after plasmapheresis. At last follow-up, renal function was stable in two of the six nonresponding patients, and four of the six had significant progression of renal disease or were receiving dialysis treatments. These studies suggest that plasmapheresis may diminish proteinuria and stabilize renal function in a small minority of patients with steroid-resistant idiopathic FSGS. However, the lack of a relationship between the removal of the circulating permeability factor and the development of remission in these patients suggests that local factors associated with advanced renal injury or systemic factors unrelated to glomerular permeability play a significant role in determining proteinuria at this late stage of the disease.

Adolescent↗

Complete regression of established murine hepatocellular carcinoma by in vivo tumor necrosis factor alpha gene transfer.

BACKGROUND & AIMS: Although tumor necrosis factor (TNF)-alpha possesses a potent antitumor activity, systemic administration of TNF-alpha causes severe side effects. To circumvent this, the efficacy of tumor cell-targeted TNF-alpha gene therapy was investigated. METHODS: Murine hepatocellular carcinoma (HCC) cells were infected with MNSM-Alb e/p-TNF-alpha retroviruses carrying the murine TNF-alpha gene under the transcriptional control of the murine albumin gene promoter, and antitumor effects induced by TNF-alpha gene transfer were examined in vitro and in vivo. RESULTS: Although MNSM-Alb e/p-TNF-alpha retrovirally infected HCC cells showed the same in vitro cell growth as parental HCC cells, they lost their tumorigenicity when implanted in syngeneic mice and induced tumor immunity against parental HCCs. The retrovirally infected HCC cells also significantly inhibited the tumorigenicity of previously implanted parental HCCs. Furthermore, intratumoral administration of MNSM-Alb e/p-TNF-alpha retroviruses showed the antitumor effect against established HCCs, resulting in significantly prolonged survival periods. Most importantly, intratumoral implantation of MNSM-Alb e/p-TNF-alpha retroviral-producing cells completely abrogated established HCCs in mice. CONCLUSIONS: These results indicate the potential efficacy of transferring the TNF-alpha gene via retroviral vectors directly into tumors for gene therapy against HCCs.

Animals↗

Serum albumin, C-reactive protein, interleukin 6, and fetuin a as predictors of malnutrition, cardiovascular disease, and mortality in patients with ESRD.

BACKGROUND: Serum albumin (S-Alb), C-reactive protein (CRP), and interleukin 6 (IL-6) predict malnutrition, atherosclerotic cardiovascular disease (CVD), and mortality in patients with end-stage renal disease (ESRD). Fetuin A, an inhibitor of vascular calcification, also is associated strongly with clinical outcome in patients with ESRD. In this study, multivariate analyses were performed to assess these 4 biomarkers as predictors of malnutrition, CVD, and mortality in patients with ESRD. METHODS: One hundred seventy-six patients with ESRD (54 +/- 12 years) underwent measurements of S-Alb, high-sensitivity CRP (hs-CRP), plasma IL-6, and fetuin A close to the start of dialysis therapy and were followed up for a median of 26 months (range, 1 to 66 months). Nutritional status was evaluated by means of subjective global assessment. CVD was defined based on medical history. Associations between biomarker levels and malnutrition, CVD, and mortality were evaluated by means of receiver operating characteristic curve, logistic regression analysis, and Cox proportional hazards model. RESULTS: All 4 biomarkers predicted malnutrition, CVD, and mortality. Multivariate analysis, according to receiver operating characteristic analysis, showed that malnutrition was predicted best by hs-CRP and IL-6 levels; CVD, by IL-6 level; and mortality, by albumin and IL-6 levels. When using the cutoff levels derived from receiver operating characteristics, logistic regression analysis showed that only hs-CRP level (odds ratio [OR], 3.6) was associated with malnutrition, and only IL-6 level (OR, 3.7) was associated with CVD. Levels of S-Alb, IL-6, and fetuin A, but not hs-CRP, were associated with increased relative risk for mortality as assessed by Cox in a model adjusting for age, sex, and diabetes mellitus. CONCLUSION: Multivariate analyses show that in patients with ESRD, malnutrition is predicted best by hs-CRP and IL-6 levels; CVD, by IL-6 level; and mortality, by S-Alb, IL-6, and fetuin A levels, but not by hs-CRP level. This comparative analysis indicates that of these biomarkers, IL-6 level may be the most reliable predictor of CVD and mortality in patients with ESRD.

Adult↗

Survival and prognostic indicators for dogs with intrahepatic portosystemic shunts: 32 cases (1990-2000).

OBJECTIVE: To determine prognostic indicators for short-term outcome and long-term survival for dogs with intrahepatic portosystemic shunts (IPSS). STUDY DESIGN: Retrospective study. ANIMALS: Thirty-two dogs of various breeds. METHODS: Clinical data extracted from medical records of dogs with IPSS were reviewed and included gender, age at surgery, weight, preoperative packed cell volume (PCV), total plasma protein concentration (TP), albumin (ALB), serum activities of alanine aminotransferase (ALT) and alkaline phosphatase (ALP), preprandial and postprandial bile acid concentrations (pre-BA, post-BA), blood urea nitrogen (BUN), glucose concentration, band neutrophils, per-rectal nuclear scintigraphy shunt fraction, whether an angiogram was performed, shunt location at surgery, whether a partial or complete attenuation of the shunt was performed, rectal temperature at the end of surgery, and duration of surgical procedure. Follow-up was determined from visits to the veterinary teaching hospital or by telephone communications with the owner or referring veterinarian. RESULTS: Median survival time was 35.68 months, and 1- and 2-year probabilities of survival were 60% and 55%, respectively. Body weight, TP, ALB, and BUN were identified as prognostic indicators for short-term outcome. PCV and TP were identified as prognostic indicators for long-term survival. CONCLUSIONS: PCV and TP were identified as prognostic indicators for long-term survival, whereas body weight, TP, ALB, and BUN were identified as indicators for short-term outcome in dogs with IPSS. Shunt location at surgery did not have any effect on short-term outcome and long-term survival. CLINICAL RELEVANCE: Total protein, ALB, BUN, and PCV can be used to determine prognosis of dogs with intrahepatic shunt.

Animals↗

A randomized, controlled trial of the effectiveness of nebulized therapy with epinephrine compared with albuterol and saline in infants hospitalized for acute viral bronchiolitis.

OBJECTIVE: In previously well infants hospitalized with acute viral bronchiolitis, the effectiveness of repeated nebulized therapy with epinephrine (EPI) was compared with treatment with albuterol (ALB) or saline placebo (PLAC). STUDY DESIGN: In this randomized, double-blind, parallel-group, controlled trial, infants received study nebulizations every 1 to 6 hours and were assessed twice daily by the research team. The primary outcome was length of hospital stay (LOS). Secondary outcomes included the time from admission until the infant had normal hydration, oxygenation, and minimal respiratory distress. RESULTS: A total of 149 infants were randomized; 50 were allocated to receive racemic EPI, 51 were given ALB, and 48 received PLAC. Baseline characteristics and pre-enrollment symptoms, signs, and therapy were similar between groups. There were no group differences in the primary outcome measure, mean LOS (hours)(+/- SD): EPI = 59.8 (62), ALB = 61.4 (54), and PLAC = 63.3 (47); P =.95 by intent-to-treat analysis. Group differences were not statistically significant in any of the secondary outcomes. CONCLUSIONS: There were no group differences in the effectiveness of therapy for infants hospitalized with bronchiolitis. Based on these results, we do not recommend routine use of either nebulized EPI or ALB in this patient group.

Acute Disease↗

Antioxidant activity of albumin-bound bilirubin.

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.

Antioxidants↗

Cellular analysis by in situ hybridization and immunoperoxidase of alpha-fetoprotein and albumin gene expression in rat liver during the perinatal period.

To analyze at the cellular level the decrease in alpha-fetoprotein (AFP) gene expression during the early postnatal growth, we searched for AFP gene transcripts by in situ hybridization using a specific cDNA probe, and for the corresponding protein by immunocytochemistry, on rat liver sections at various times of the perinatal period. The relative number of mRNA sequences was evaluated by Northern blot analysis. Albumin (ALB) gene expression was studied simultaneously with the same techniques. In 17-19-d-old fetuses all hepatocytes express simultaneously, for both genes, the mRNAs and the corresponding proteins. During the first postnatal weeks, at a time when the global number of AFP mRNA molecules decreases, all hepatocytes still contain cytoplasmic transcripts and protein. A zonal heterogeneity in the level of AFP gene expression develops around the first week, a higher number of gene products being detected in perivenous than in periportal hepatocytes. This heterogeneity persists until the fourth week when AFP mRNA sequences and protein are barely detectable. All hepatocytes express the ALB gene after birth, but at around the second week, a periportal intensification of the in situ hybridization signal and immunostaining becomes apparent. Our data indicate that co-expression of the AFP and ALB genes by all hepatocytes is a normal step in liver ontogeny; the diminution of AFP gene expression after birth is not the result of the disappearance of specialized cell clones; and zonal quantitative differences in the level of AFP and ALB gene expression are observed within the maturing liver lobule.

Albumins↗

Monitoring of aluminum in whole blood, plasma, serum, and water by a single procedure using flameless atomic absorption spectrophotometry.

A simple, time-saving procedure to measure aluminum (AI) in whole blood, plasma, and water samples of low ionic strength by flameless atomic absorption spectrometry is presented. With this procedure, an analagous pretreatment is given to all samples. Moreover, the pretreated samples are analyzed using an identical program of the atomic absorption spectrophotometer. The detection limit is 1.3 micrograms/L for aqueous solutions and 1.9 micrograms/L, 1.8 micrograms/L, and 2.3 microL for serum, plasma, and blood samples respectively. The precision of the method varies between 2.8% and 4.2% of all analyses. Using this method, a comparison was made between Al levels in whole blood (AlB) and plasma (AlP) in rats and AlB and AlP in renal patients. The AlB and AlP were strongly correlated. It is concluded that the monitoring of AlB may have a similar prognostic value for toxicity as the monitoring of AlP, but more experimental advantages.

Aluminum↗

Reverse white-coat effect as an independent risk for microalbuminuria in treated hypertensive patients.

BACKGROUND: The influence of the converse phenomenon of white-coat hypertension called 'reverse white-coat hypertension' or 'masked hypertension' on hypertensive target organ damage has not been fully elucidated. The present study assessed the hypothesis that this phenomenon may specifically associate with microalbuminuria, a marker of early renal damage, in treated hypertension. METHODS: A total of 267 treated essential hypertensive patients (133 men and 134 women; mean age, 66 years) without renal insufficiency or macroalbuminuria were enrolled in this study. Patients were classified into three groups by the difference between office and day-time ambulatory systolic blood pressure (BP) levels; i.e. subjects with white-coat effect (W group: office--day-time systolic BP > or =20 mmHg, n = 48), with reverse white-coat effect (R group: office - day-time systolic BP < - 10 mmHg, n = 43) and without white-coat or reverse white-coat effect (N group: -10 mmHg < or = office--day-time systolic BP <20 mmHg, n = 176). The urinary albumin (U-Alb) level was measured as the albumin to creatinine excretion ratio in the urine. Microalbuminuria was defined as U-Alb of > or =30 and <300 mg/g Cr. RESULTS: R group had a well-controlled office BP (130/77 mmHg), but their day-time BP (148/87 mmHg) was elevated compared with the other two groups. The levels of U-Alb excretion in N group, W group and R group were 12.3 (8.4, 25.6), 16.0 (10.5, 31.7) and 24.3 (10.2, 79.7) mg/g Cr [median (interquartile range)], respectively. Both U-Alb level and prevalence of microalbuminuria were significantly greater in R group than in N group. Multivariate analyses revealed that the presence of reverse white-coat effect, but not white-coat effect, was a significant predictor for microalbuminuria, independent of various clinical variables including ambulatory BP levels (odds ratio 2.63 vs N group, P = 0.02). CONCLUSION: These findings suggest that the presence of reverse white-coat effect may be an independent risk for early renal damage in treated hypertensive patients.

Adult↗

Human plasma fibronectin possesses second binding site(s) to Staphylococcus aureus on its C-terminal region.

The existence of a second binding site to Staphylococcus aureus on fibronectin was explored by using a recombinant protein, alb-FnBPA, which was obtained from an Escherichia coli clone containing a part of the gene for fibronectin-binding protein of S. aureus. Limited digestion with trypsin produced a 215K fragment from the B chain of fibronectin by releasing an N-terminal 32 kDa region. This C-terminal large fragment captured alb-FnBPA in spite of lacking the N-terminal binding region to S. aureus. This treatment also produced a 185K fragment from A chain by releasing N-terminal 32 kDa and C-terminal 37 kDa regions, and the 185K fragment possessed no binding ability. Thermolysin digestion was also performed to investigate the effect on the binding of releasing the C-terminal region from both of the chains and to locate the binding region to alb-FnBPA on the tryptic 215K fragment. But this digestion produced no fragment binding to alb-FnBPA except for the N-terminal 24K and its transient precursory fragments. These results indicate that both the N-terminal and the C-terminal regions of fibronectin bind to S. aureus, and suggest that the binding appears to involve cooperation between type III repeats and C-terminal type I repeats.

Binding Sites↗