Showing papers on "Serum albumin published in 2010"

Pretreatment serum albumin as a predictor of cancer survival: A systematic review of the epidemiological literature

Abstract: Background: There are several methods of assessing nutritional status in cancer of which serum albumin is one of the most commonly used. In recent years, the role of malnutrition as a predictor of survival in cancer has received considerable attention. As a result, it is reasonable to investigate whether serum albumin has utility as a prognostic indicator of cancer survival in cancer. This review summarizes all available epidemiological literature on the association between pretreatment serum albumin levels and survival in different types of cancer. Methods: A systematic search of the literature using the MEDLINE database (January 1995 through June 2010) to identify epidemiologic studies on the relationship between serum albumin and cancer survival. To be included in the review, a study must have: been published in English, reported on data collected in humans with any type of cancer, had serum albumin as one of the or only predicting factor, had survival as one of the outcome measures (primary or secondary) and had any of the following study designs (case-control, cohort, cross-sectional, case-series prospective, retrospective, nested case-control, ecologic, clinical trial, meta-analysis). Results: Of the 29 studies reviewed on cancers of the gastrointestinal tract, all except three found higher serum albumin levels to be associated with better survival in multivariate analysis. Of the 10 studies reviewed on lung cancer, all excepting one found higher serum albumin levels to be associated with better survival. In 6 studies reviewed on female cancers and multiple cancers each, lower levels of serum albumin were associated with poor survival. Finally, in all 8 studies reviewed on patients with other cancer sites, lower levels of serum albumin were associated with poor survival. Conclusions: Pretreatment serum albumin levels provide useful prognostic significance in cancer. Accordingly, serum albumin level could be used in clinical trials to better define the baseline risk in cancer patients. A critical gap for demonstrating causality, however, is the absence of clinical trials demonstrating that raising albumin levels by means of intravenous infusion or by hyperalimentation decreases the excess risk of mortality in cancer.

Resveratrol, genistein, and curcumin bind bovine serum albumin.

Abstract: We report the complexation of bovine serum albumin (BSA) with resveratrol, genistein, and curcumin, at physiological conditions, using constant protein concentration and various polyphenol contents. FTIR, CD, and fluorescence spectroscopic methods were used to analyze the ligand binding mode, the binding constant, and the effects of complexation on BSA stability and conformation. Structural analysis showed that polyphenols bind BSA via hydrophilic and hydrophobic interactions with the number of bound polyphenol (n) being 1.30 for resveratrol-BSA, 1.30 for genistein-BSA, and 1.0 for curcumin-BSA. The polyphenol-BSA binding constants were K(Res-BSA) = 2.52(+/-0.5) x 10(4) M(-1), K(Gen-BSA) = 1.26(+/-0.3) x 10(4) M(-1), and K(Cur-BSA) = 3.33(+/-0.8) x 10(4) M(-1). Polyphenol binding altered BSA conformation with a major reduction of alpha-helix and an increase in beta-sheet and turn structures, indicating a partial protein unfolding.

Reassessment of Albumin as a Nutritional Marker in Kidney Disease

Abstract: The decision by nephrologists, renal dietitians, federal agencies, health care payers, large dialysis organizations, and the research community to embrace serum albumin as an important index of nutrition and clinical performance is based on numerous misconceptions. Patients with analbuminemia are not malnourished and individuals with simple malnutrition are rarely hypoalbuminemic. With the possible exception of kwashiorkor, a rare nutritional state, serum albumin is an unreliable marker of nutritional status. Furthermore, nutritional supplementation has not been clearly shown to raise levels of serum albumin. The use of serum albumin as a quality care index is also problematic. It has encouraged a reflexive reliance on expensive and unproven interventions such as dietary supplements and may lead to adverse selection of healthier patients by health care providers. The authors offer a rationale for considering albumin as a marker of illness rather than nutrition. Viewed in this manner, hypoalbuminemia may offer an opportunity to improve patient well-being by identifying and treating the underlying disorder.

Synthesis of a novel hydrazone derivative and biophysical studies of its interactions with bovine serum albumin by spectroscopic, electrochemical, and molecular docking methods

Abstract: Hydrazone derivatives possess potential antitumor activities based on modulation of the iron metabolism in cancer cell. A novel hydrazone, N′-(2,4-dimethoxybenzylidene)-2-hydroxybenzohydrazide (DBH), has been synthesized and characterized, which is an analogue of 311 possessing potent anticancer activity. The interactions between DBH and bovine serum albumin (BSA) have been investigated systematically by fluorescence, molecular docking, circular dichroism (CD), UV−vis absorption, and electrochemical impedance spectroscopy (EIS) methods under physiological conditions. The fluorescence quenching observed is attributed to the formation of a complex between BSA and DBH, and the reverse temperature effect of the fluorescence quenching has been found and discussed. The primary binding pattern is determined by hydrophobic interaction occurring in Sudlow’s site I of BSA. DBH could slightly change the secondary structure and induce unfolding of the polypeptides of protein. An average binding distance of ∼4.0 nm ha...

Serum albumin concentration: a predictive factor of infliximab pharmacokinetics and clinical response in patients with ulcerative colitis.

Abstract: Objectives: Infliximab, an IgG 1 monoclonal antibody (mab), has large inter-individual serum concentration variability. The objective was to determine the extent of the association of baseline albumin concentration and infliximab disposition in patient with ulcerative colitis. Method: Data from 728 patients with ulcerative colitis from two clinical trials were analyzed to evaluate trends between infliximab pharmacokinetics and serum albumin, or liver or kidney function. Response in the placebo and treated groups were compared by baseline serum albumin concentrations (SAC) groups. Results: Patients with higher SAC maintained higher infliximab concentrations, lower clearance, and longer half-life than patients with lower SAC. When analyzed by SAC quartiles, patients in the highest quartile had several-fold greater trough infliximab concentrations when compared with those in the lowest quartile. These observations were consistent in both studies and at different dose levels. Generally, clinical response in patients did not vary with SAC when the SAC was within the normal range, apparently because serum infliximab concentrations remained at therapeutic levels. However, patients with SAC lower than the normal laboratory reference range had much lower median serum infliximab concentrations and lower response rates compared with patients within normal SAC. Infliximab pharmacokinetics did not correlate with SGOT or creatinine clearance. Conclusions: It is hypothesized that the common rescue pathway for both albumin and IgG involving the neonatal Fc receptor may be responsible for the relationship between serum albumin and serum infliximab levels. Baseline albumin level may serve as a valuable and convenient measure of mab pharmacokinetic expectations in these patients.

Interaction between a potent corticosteroid drug – Dexamethasone with bovine serum albumin and human serum albumin: A fluorescence quenching and fourier transformation infrared spectroscopy study

Abstract: This study was designed to examine the interaction of dexamethasone (DEX) with bovine serum albumin (BSA) and human serum albumin (HSA) under physiological conditions with drug concentrations in the range of 2.5-20 microM and BSA/HSA was fixed at 5.0 microM. Spectroscopic analysis of the emission quenching at different temperatures revealed that the quenching mechanism of serum albumin by dexamethasone is static quenching mechanism. The binding sites number, n and binding constant, K were obtained at various temperatures. The distance r between dexamethasone and the protein was evaluated according to the theory of Foster energy transfer. The result of fluorescence spectra UV-vis absorption spectra and FT-IR spectra showed that the conformation of bovine serum albumin and human serum albumin has been changed in the presence of dexamethasone. The thermodynamic parameters, free energy change (DeltaG(0)), enthalpy change (DeltaH(0)) and entropy change (DeltaS(0)) for BSA-DEX and HSA-DEX were calculated according to van't Hoff equation and discussed.

Bovine and human serum albumin interactions with 3-carboxyphenoxathiin studied by fluorescence and circular dichroism spectroscopy.

Abstract: The interactions of 3-carboxyphenoxathiin with Bovine Serum Albumin (BSA) and Human Serum Albumin (HSA) have been studied by fluorescence and circular dichroism spectroscopy. The binding of 3-carboxyphenoxathiin quenches the BSA and HSA fluorescence, revealing a 1:1 interaction with a binding constant of about 10(5) M(-1). In addition, according to the synchronous fluorescence spectra of BSA and HSA in presence of 3-carboxyphenoxathiin, the tryptophan residues of the proteins are most perturbed by the binding process. Finally, the distance between the acceptor, 3-carboxyphenoxathiin, and the donor, BSA or HSA, was estimated on the basis of the Forster resonance energy transfer (FRET). The fluorescence results are correlated with those obtained from the circular dichroism spectra, which reveal the change of the albumin conformation during the interaction process.

Hypoalbuminemia and acute kidney injury: a meta-analysis of observational clinical studies

Abstract: To test the hypothesis that hypoalbuminemia is independently associated with increased risk of acute kidney injury (AKI). A meta-analysis was performed of observational clinical studies evaluating the relationship between serum albumin level and the occurrence of AKI by multivariate methods. Additionally, the impact was assessed of lower serum albumin on mortality in patients who developed AKI. Eligible studies were sought by multiple methods, and adjusted odds ratios (OR) were quantitatively combined using a random effects model. Seventeen clinical studies with 3,917 total patients were included: 11 studies (6 in surgical or intensive care unit patients and 5 in other hospital settings) evaluating the influence of serum albumin on AKI incidence and 6 studies describing the relationship between serum albumin and mortality among patients who had developed AKI. Lower serum albumin was an independent predictor both of AKI and of death after AKI development. With each 10 g L−1 serum albumin decrement, the odds of AKI increased by 134%. The pooled OR for AKI was 2.34 with a 95% confidence interval (CI) of 1.74–3.14. Among patients who had developed AKI, the odds of death rose 147% (pooled OR 2.47, 95% CI 1.51–4.05) with each 10 g L−1 serum albumin decrement. This meta-analysis provides evidence that hypoalbuminemia is a significant independent predictor both of AKI and of death following AKI development. Serum albumin determinations may be of utility in identifying patients at increased risk for AKI or for death after AKI. Controlled studies are warranted to assess interventions aimed at correcting hypoalbuminemia.

Transport of therapeutic vanadium and ruthenium complexes by blood plasma components.

Abstract: Low molecular weight and high molecular weight metal ion binders present in blood plasma are shortly described. The binding of vanadium and ruthenium complexes by these components has received much attention, namely their interactions with human serum albumin and transferrin, and these studies are critically reviewed. The influence of the protein binding on the bioavailability of the prospective drugs, namely on the transport by blood plasma and uptake by cells is also discussed. It is concluded that vanadium compounds are mainly transported in blood by transferrin, but that no study has properly addressed the influence of albumin and transferrin in the vanadium uptake by cells. Ruthenium complexes bind strongly to HSA, most likely at the level of His residues, leading to the formation of stable adducts. If the kinetics of binding to this protein is fast enough, probably they are mainly transported by this serum protein. Nevertheless, at least for a few Ru III -complexes, hTf seems to play an active role in the uptake of ruthenium, while HSA may provide selectivity and higher activity for the compounds due to an enhanced permeability effect.

Determination of the Affinity of Drugs toward Serum Albumin by Measurement of the Quenching of the Intrinsic Tryptophan Fluorescence of the Protein

Abstract: Binding of new chemical entities to serum proteins is an issue confronting pharmaceutical companies during development of potential therapeutic agents. Most drugs bind to the most abundant plasma protein, human serum albumin (HSA), at two major binding sites. Excepting fluorescence spectroscopy, existing methods for assaying drug binding to serum albumin are insensitive to higher-affinity compounds and can be labour-intensive, time-consuming, and usually require compound-specific assays. This led us to examine alternative ways to measure drug-albumin interaction. One method described here uses fluorescence quenching of the single tryptophan (Trp) residue in HSA excited at 295 nm to measure drug-binding affinity. Unfortunately, many compounds absorb, fluoresce, or both, in this UV wavelength region of the spectrum. Several types of binding phenomenon and spectral interference were identified by use of six structurally unrelated compounds and the equations necessary to make corrections mathematically were derived and applied to calculate binding constants accurately. The general cases were: direct quenching of Trp fluorescence by optically transparent ligands with low or high affinities; binding of optically transparent, non-fluorescent ligands to two specific sites where both sites or only one site result in Trp fluorescence quenching; and chromophores whose absorption either overlaps the Trp emission and quenches by energy transfer or absorbs light at the Trp fluorescence excitation wavelength producing absorptive screening as well as fluorescence quenching. Unless identification of the site specificity of drug binding to serum albumin is desired, quenching of the Trp fluorescence of albumin by titration with ligand is a rapid and facile method for determining the binding affinities of drugs for serum albumin.

Molecular Dynamics Simulation and Binding Studies of β-Sitosterol with Human Serum Albumin and Its Biological Relevance

Abstract: Beta-sitosterol is a naturally occurring phytosterol that is widely used to cure atherosclerosis, diabetes, cancer, and inflammation and is also an antioxidant. Here, we studied the interaction of beta-sitosterol, isolated from the aerial roots of Ficus bengalensis, with human serum albumin (HSA) at physiological pH 7.2 by using fluorescence, circular dichroism (CD), molecular docking, and molecular dynamics simulation methods. The experimental results show that the intrinsic fluorescence of HSA is quenched by addition of beta-sitosterol through a static quenching mechanism. The binding constant of the compound to HSA, calculated from fluorescence data, was found to be K(beta-sitosterol) = 4.6 +/- 0.01 x 10(3) M(-1), which corresponds to -5.0 kcal M(-1) of free energy. Upon binding of beta-sitosterol to HSA, the protein secondary structure was partially unfolded. Specifically, the molecular dynamics study makes an important contribution to understanding the effect of the binding of beta-sitosterol on conformational changes of HSA and the stability of a protein-drug complex system in aqueous solution. Molecular docking studies revealed that the beta-sitosterol can bind in the large hydrophobic cavity of subdomain IIA, mainly by the hydrophobic interaction but also by hydrogen bond interactions between the hydroxyl (OH) group of carbon-3 of beta-sitosterol to Arg(257), Ser(287), and Ala(261) of HSA, with hydrogen bond distances of 1.9, 2.4, and 2.2 A, respectively.

Noncovalent Interactions of Long-Chain Perfluoroalkyl Acids with Serum Albumin

Abstract: Preferential distribution of long-chain perfluoroalkyl acids (PFAAs) in the liver, kidney, and blood of organisms highlights the importance of PFAA-protein interactions in PFAA tissue distribution patterns. A serum protein association constant may be a useful parameter to characterize the bioaccumulative potential and in vivo bioavailability of PFAAs. In this work, association constants (Ka) and binding stoichiometries for PFAA-albumin complexes are quantified over a wide range of PFAA:albumin mole ratios. Primary association constants for perfluorooctanoate (PFOA) or perfluorononanoate (PFNA) with the model protein bovine serum albumin (BSA) determined via equilibrium dialysis are on the order of 106 M−1 with one to three primary binding sites. PFNA was greater than 99.9% bound to BSA or human serum albumin (HSA) at a physiological PFAA:albumin mole ratio ( 4). Nanoelectrospray ionization mass spectrometry (nanoESI-MS) data ...

Human serum albumin nanoparticles as an efficient noscapine drug delivery system for potential use in breast cancer: preparation and in vitro analysis

Abstract: Drug delivery systems such as nanoparticles can provide enhanced efficacy for anticancer agents. Noscapine, a widely used cough suppressant for decades has recently been shown to cause significant inhibition and regression of tumor volumes without any detectable toxicity in cells or tissues. Nanoparticles made of human serum albumin (HSA) represent promising strategy for targeted drug delivery to tumor cells by enhancing the drug’s bioavailability and distribution, and reducing the body’s response towards drug resistance. In the present study, we report for the first time the incorporation and delivery of noscapine-loaded HSA nanoparticles to tumor cells. The nanoparticles were designed and optimized to achieve a particle size in the range of 150–300 nm with a drug-loading efficiency of 85%–96%. The nanoparticles were evaluated in vitro for their anticancer activity and efficacy on breast cancer cells.

Binding of Perfluorocarboxylates to Serum Albumin: A Comparison of Analytical Methods

Abstract: Perfluorochemicals are globally pervasive contaminants that are persistent, bioaccumulative, and toxic Perfluorocarboxylic acids (PFCAs) with 8−13 carbons accumulate in the liver and blood of aquatic organisms; PFCA−protein interactions may explain this accumulation pattern Here, the interactions between PFCAs with 8−11 carbons and serum albumin are examined using three experimental approaches: surface tension titrations, 19F NMR spectroscopy, and fluorescence spectroscopy Surface tension titrations indicate complex formation at high (mM) PFCA concentrations Secondary association constants ranging from 102 to 104 M−1 were determined from 19F NMR titrations at high PFCA:albumin mole ratios Fluorescence measurements indicate that PFCA−albumin interactions alter the protein conformation at low PFCA:albumin mole ratios (up to 5:1) and suggest two binding classes with association constants around 105 and 102 M−1 While 19F NMR and fluorescence provide both qualitative and quantitative information about PF

The influence of surface composition of nanoparticles on their interactions with serum albumin.

Abstract: Interactions between differently functionalised silver and gold nanoparticles (NPs) as well as polystyrene nanoparticles with bovine serum albumin (BSA) are studied using circular dichroism (CD) spectroscopy. It is found that the addition of NPs to the protein solution destroys part of the helical secondary structure of the protein as a result of surface adsorption. From the loss of free protein and hence the extent of their structural change adsorption equilibrium constants are derived. The results reveal that citrate-coated gold and silver NPs exhibit much stronger interactions with BSA than polymeric or polymer-coated metallic NPs. It is therefore concluded that for the particles considered, the influence of surface composition on the interaction behaviour dominates that of the core.

Erythrocytes serve as a reservoir for cellular and extracellular sphingosine 1-phosphate

Abstract: Sphingosine 1-phosphate (S1P) in blood is phosphorylated, stored, and transported by red blood cells (RBC). Release of S1P from RBC into plasma is a regulated process that does not occur in plasma- or serum-free media. Plasma fractionation and incubations with isolated and recombinant proteins identified high density lipoprotein (HDL) and serum albumin (SA) as non-redundant endogenous triggers for S1P release from RBC. S1P bound to SA and HDL was able to stimulate the S1P(1) receptor in calcium flux experiments. The binding capability of acceptor molecules triggers S1P release, as demonstrated with the anti-S1P antibody Sphingomab. More S1P was extracted from RBC membranes by HDL than by SA. Blood samples from anemic patients confirmed a reduced capacity for S1P release in plasma. In co-cultures of RBC and endothelial cells (EC), we observed transcellular transportation of S1P as a second function of RBC-associated S1P in the absence of SA and HDL and during tight RBC-EC contact, mimicking conditions in tissue interstitium and capillaries. In contrast to S1P bound to SA and HDL, RBC-associated S1P was significantly incorporated by EC after S1P lyase (SGPL1) inhibition. RBC-associated S1P, therefore, has two functions: (1) It contributes to the cellular pool of SGPL1-sensitive S1P in tissues after transcellular transportation and (2) it helps maintain extracellular S1P levels via SA and HDL independently from SGPL1 activity.

The effects of affinity and valency of an albumin-binding domain (ABD) on the half-life of a single-chain diabody-ABD fusion protein

Abstract: Fusion of small recombinant antibody fragments to an albumin-binding domain (ABD) from streptococcal protein G strongly extends their plasma half-life. This ABD binds with nanomolar affinity to human (HSA) and mouse serum albumin (MSA). It was speculated that an increase in albumin-binding affinity should lead to a further increase in half-life. In the present study, we analyzed the effects of affinity and valency of the ABD on the pharmacokinetic properties of a bispecific single-chain diabody (scDb), applied previously to investigate various half-life extension strategies. The scDb is directed against carcinoembryonic antigen (CEA) and CD3 capable of mediating T cell retargeting to tumor cells. Two scDb derivatives with increased (scDb-ABD-H) and decreased (scDb-ABD-L) affinity as well as an scDb molecule fused to two ABD (scDb-ABD(2)) were generated and produced in mammalian cells. The altered binding of these constructs to HSA and MSA was confirmed by ELISA and quartz crystal microbalance measurements. All constructs bound efficiently to CEA and CD3-positive cells and were able to activate T cells in a target cell-dependent manner, although T cell activation was reduced in the presence of serum albumin. All three derivatives showed a strongly increased half-life in mice as compared with scDb. Compared with the wild-type scDb-ABD, the half-life of scDb-ABD-H exhibited a prolonged half-life and scDb-ABD-L a reduced half-life, while the half-life scDb-ABD(2) was almost identical to that of scDb-ABD. However, these changes were only moderate, indicating that the half-life-extending property of the ABD in mice is only weakly influenced by affinity for serum albumin or valency of albumin binding.

A1C but Not Serum Glycated Albumin Is Elevated Because of Iron Deficiency in Late Pregnancy in Diabetic Women

Abstract: OBJECTIVE We have already reported that A1C is elevated because of iron deficiency in late pregnancy among nondiabetic pregnant women. This report examined whether the same phenomenon is observed in pregnant women with diabetes. RESEARCH DESIGN AND METHODS This longitudinal study was conducted in 17 pregnant women with diabetes (20-35 weeks of pregnancy). A1C, serum glycated albumin, erythrocyte indexes, and iron metabolism indexes were measured. RESULTS A1C levels were significantly increased in late pregnancy, whereas serum glycated albumin showed no significant changes. Glycated albumin/A1C ratio, mean corpuscular hemoglobin, serum transferrin saturation, and serum ferritin were significantly decreased in late pregnancy. Serum transferrin saturation showed a significant positive correlation with glycated albumin/A1C ratio. CONCLUSIONS A1C levels, but not serum glycated albumin levels, are elevated in late pregnancy because of iron deficiency in diabetic women. Serum glycated albumin may offer an adequate marker for glycemic control during pregnancy.

Human serum albumin nanoparticles modified with apolipoprotein A-I cross the blood-brain barrier and enter the rodent brain

Abstract: Nanoparticles made of human serum albumin (HSA) and modified with apolipoproteins have previously been shown to transport drugs, which normally do not enter the brain, across the blood-brain barrier (BBB). However the precise mechanism by which nanoparticles with different apolipoproteins on their surface can target to the brain, as yet, has not been totally elucidated. In the present study, HSA nanoparticles with covalently bound apolipoprotein A-I (Apo A-I) as a targetor for brain capillary endothelial cells were injected intravenously into SV 129 mice and Wistar rats. The rodents were sacrificed after 15 or 30 min, and their brains were examined by transmission electron microscopy. Apo A-I nanoparticles could be found inside the endothelial cells of brain capillaries as well as within parenchymal brain tissue of both, mice and rats, whereas control particles without Apo A-I on their surface did not cross the BBB during our experiments. The maintenance of tight junction integrity and barrier function during treatment with nanoparticles was demonstrated by perfusion with a fixative containing lanthanum nitrate as an electron dense marker for the permeability of tight junctions.