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Showing papers on "Serum albumin published in 2013"


Journal ArticleDOI
TL;DR: The manipulation of the albumin-FcRn interaction will facilitate the modulation of the circulatory half-life ofalbumin-enabled drugs, leading to superior pharmacokinetics tailored to the disease state and increased patient compliance.

366 citations


Journal ArticleDOI
TL;DR: The thorough understanding of metal binding properties of serum albumin, including the competition of various metal ions for specific binding sites is important for biomedical issues, such as new disease markers and design of metal-based drugs.

355 citations


Journal ArticleDOI
TL;DR: The present review discusses recent findings regarding the nature of drug binding sites, drug-albumin binding in certain diseased states or in the presence of co administered drugs, and the potential of utilizing albumin-drug interactions in clinical applications.

344 citations


Journal ArticleDOI
12 Mar 2013-PLOS ONE
TL;DR: Residual inflammation at ICU discharge assessed using theCRP/albumin ratio is an independent risk factor for mortality at 90 days in septic patients and the use of the CRP/ Albumin ratio as a long-term marker of prognosis provides more consistent results than standard CRP values alone.
Abstract: Introduction Residual inflammation at ICU discharge may have impact upon long-term mortality. However, the significance of ongoing inflammation on mortality after ICU discharge is poorly described. C-reactive protein (CRP) and albumin are measured frequently in the ICU and exhibit opposing patterns during inflammation. Since infection is a potent trigger of inflammation, we hypothesized that CRP levels at discharge would correlate with long-term mortality in septic patients and that the CRP/albumin ratio would be a better marker of prognosis than CRP alone.

288 citations


Journal ArticleDOI
20 Nov 2013-ACS Nano
TL;DR: The disparate effects of a givenprotein corona on particle-cell interactions are demonstrated, highlighting the correlation between protein corona conformation in situ and relevant biological characteristics for biological functionalities.
Abstract: Many biomolecules, mainly proteins, adsorb onto polymer particles to form a dynamic protein corona in biological environments. The protein corona can significantly influence particle-cell interactions, including internalization and pathway activation. In this work, we demonstrate the differential roles of a given protein corona formed in cell culture media in particle uptake by monocytes and macrophages. By exposing disulfide-stabilized poly(methacrylic acid) nanoporous polymer particles (PMASH NPPs) to complete cell growth media containing 10% fetal bovine serum, a protein corona, with the most abundant component being bovine serum albumin, was characterized. Upon adsorption onto the PMASH NPPs, native bovine serum albumin (BSA) was found to undergo conformational changes. The denatured BSA led to a significant decrease in internalization efficiency in human monocytic cells, THP-1, compared with the bare particles, due to reduced cell membrane adhesion. In contrast, the unfolded BSA on the NPPs triggered class A scavenger receptor-mediated phagocytosis in differentiated macrophage-like cells (dTHP-1) without a significant impact on the overall internalization efficiency. Taken together, this work demonstrates the disparate effects of a given protein corona on particle-cell interactions, highlighting the correlation between protein corona conformation in situ and relevant biological characteristics for biological functionalities.

246 citations


Journal ArticleDOI
TL;DR: In this paper, the interaction of various nanomaterials, antibiotics, anticancer drugs, anti-inflammatory agents, dyes, flavonoids, and certain noxious materials with serum albumin is discussed.
Abstract: The interactions of human and bovine serum albumins (HSA and BSA) with various drugs and nanomaterials receive great attention in the recent years owing to their significant impact in the biomedical field. Although there are various techniques available for studying such interactions, fluorescence spectroscopy is the most appealing one due to its high sensitivity and straightforwardness. Detailed information about the interactions of drugs and nanomaterials with serum can be deducted from a mass of information accumulated by the fluorescence quenching studies. The present review emphasizes the interaction of various nanomaterials, antibiotics, anticancer drugs, anti-inflammatory agents, dyes, flavonoids, and certain noxious materials with HSA and BSA. In particular, we focus on the interactions of serum albumin with nanomaterials having different size and stabilizing agents with various receptors. This review helps in understanding the structural features of drugs/nanomaterials crucial for not only their affinity for serum albumin but also their optimum pharmacological activities.

186 citations


Journal ArticleDOI
TL;DR: Hydrophilicity, high biocompatibility, and controllable drug loading and release render BNC an innovative and attractive biopolymer for controlled drug delivery.

165 citations


Journal ArticleDOI
TL;DR: The findings suggest that a redox change in HSA is related to the oxidation of several amino acid residues by different oxidants, and the ratio of the oxidized form to the normal form of albumin (HMA/HNA) could serve as a useful marker for evaluating systemic redox states, which would be useful for the evaluation of disease progression and therapeutic efficacy.

163 citations


Journal ArticleDOI
TL;DR: Serum %C-Alb is identified as a risk factor for mortality in patients with ESRD and it is proposed that this risk factor may be modifiable with supplemental amino acid therapy.
Abstract: Urea, the toxic end product of protein catabolism, is elevated in end-stage renal disease (ESRD), although it is unclear whether or how it contributes to disease. Urea can promote the carbamylation of proteins on multiple lysine side chains, including human albumin, which has a predominant carbamylation site on Lys(549). The proportion of serum albumin carbamylated on Lys(549) (%C-Alb) correlated with time-averaged blood urea concentrations and was twice as high in ESRD patients than in non-uremic subjects (0.90% versus 0.42%). Baseline %C-Alb was higher in ESRD subjects who died within 1 year than in those who survived longer than 1 year (1.01% versus 0.77%) and was associated with an increased risk of death within 1 year (hazard ratio, 3.76). These findings were validated in an independent cohort of diabetic ESRD subjects (hazard ratio, 3.73). Decreased concentrations of serum amino acids correlated with higher %C-Alb in ESRD patients, and mice with diet-induced amino acid deficiencies exhibited greater susceptibility to albumin carbamylation than did chow-fed mice. In vitro studies showed that amino acids such as cysteine, histidine, arginine, and lysine, as well as other nucleophiles such as taurine, inhibited cyanate-induced C-Alb formation at physiologic pH and temperature. Together, these results suggest that chronically elevated urea promotes carbamylation of proteins in ESRD and that serum amino acid concentrations may modulate this protein modification. In summary, we have identified serum %C-Alb as a risk factor for mortality in patients with ESRD and propose that this risk factor may be modifiable with supplemental amino acid therapy.

160 citations


Journal ArticleDOI
TL;DR: It is necessary to give a more detailed explanation of albumin and its relations with oxidative stress and its interactions with Reactive Oxygen Species.
Abstract: Human serum albumin, a negative acute phase reactant and marker of nutritive status, presents at high concentrations in plasma. Albumin has always been used in many clinical states especially to improve circulatory failure. It has been showed that albumin is involved in many bioactive functions such as regulation of plasma osmotic pressure, binding and transport of various endogenous or exogenous compounds, and finally extracellular antioxidant defenses. Molecules like transferrin, caeruloplasmin, haptoglobin, uric acid, bilirubin, alpha-tocopherol, glucose, and albumin constitute extracellular antioxidant defenses in blood plasma but albumin is the most potent one. Most of the antioxidant properties of albumin can be attributed to its unique biochemical structure. The protein possesses antioxidant properties such as binding copper tightly and iron weakly, scavenging free radicals, e.g., hypochlorous acid (HOCl) and Peroxynitrite (ONOOH) and providing thiol group (-SH). Whether it is chronic or acute, during many pathological conditions, biomarkers of oxidative protein damage increase and this observation continues with considerable oxidation of human serum albumin. There is an important necessity to specify its interactions with Reactive Oxygen Species. Generally, it may lower the availability of pro-oxidants and be preferentially oxidized to protect other macromolecules but all these findings make it necessary that researchers give a more detailed explanation of albumin and its relations with oxidative stress.

128 citations


Journal ArticleDOI
TL;DR: Subdomain IB is a major binding site for complex heterocyclic molecules in serum albumin and has important implications for drug design and development.

Journal ArticleDOI
TL;DR: Evidence of a transcytosis within the kidney tubular system that protects albumin and IgG from lysosomal degradation, allowing these proteins to be recycled intact is provided.
Abstract: Under physiologic conditions, significant amounts of plasma protein pass the renal filter and are reabsorbed by proximal tubular cells, but it is not clear whether the endocytosed protein, particularly albumin, is degraded in lysosomes or returned to the circulatory system intact. To resolve this question, a transgenic mouse with podocyte-specific expression of doxycycline-inducible tagged murine albumin was developed. To assess potential glomerular backfiltration, two types of albumin with different charges were expressed. On administration of doxycycline, podocytes expressed either of the two types of transgenic albumin, which were secreted into the primary filtrate and reabsorbed by proximal tubular cells, resulting in serum accumulation. Renal transplantation experiments confirmed that extrarenal transcription of transgenic albumin was unlikely to account for these results. Genetic deletion of the neonatal Fc receptor (FcRn), which rescues albumin and IgG from lysosomal degradation, abolished transcytosis of both types of transgenic albumin and IgG in proximal tubular cells. In summary, we provide evidence of a transcytosis within the kidney tubular system that protects albumin and IgG from lysosomal degradation, allowing these proteins to be recycled intact.

Journal ArticleDOI
TL;DR: It is found that fatty acids (FAs) compete with FcRn, revealing a clash between ligand binding and recycling, and that high-affinity HSA variants have significantly increased circulating half-lives in mice and monkeys.

Journal ArticleDOI
TL;DR: Two protein crystal structures of HSA in complex with either glucose or fructose reveal the presence of linear forms of sugar for both monosaccharides and propose a mechanism for glucose ring opening involving both residues Lys-195 and Lys-199.

Journal ArticleDOI
TL;DR: The ultrafiltration–HPLC technique reliably measures free serum concentrations of indoxyl sulfate and p‐cresyl sulfates and indicates that competition for this binding site could be used to augment free solute concentrations during dialysis, thus improving epuration.
Abstract: Indoxyl sulfate and p-cresyl sulfate are two uremic retention solutes implicated in the uremic syndrome. Removal during dialysis is limited, mainly due to protein binding. Binding characteristics to healthy albumin have recently been characterized. Whether uremia alters the binding characteristics of albumin is currently unknown. Moreover, protein binding values previously determined with ultrafiltration are in sharp contrast to recently reported values based on microcalorimetry. In the present study, indoxyl sulfate and p-cresyl sulfate binding were therefore quantified using both equilibrium dialysis and ultrafiltration. Deming regression demonstrated good agreement between equilibrium dialysis and ultrafiltration. Free serum concentrations of indoxyl sulfate (+26.6%) and p-cresyl sulfate (+19.7%) were slightly higher at body temperature compared with at room temperature. To investigate binding kinetics, the plasma of healthy individuals or hemodialysis patients was titrated with albumin solutions. Theoretical models of protein binding were fitted to observed titration curves. Binding coefficients of both toxins were highest in purified albumin, and were reduced from healthy to uremic plasma. In conclusion, the ultrafiltration-HPLC technique reliably measures free serum concentrations of indoxyl sulfate and p-cresyl sulfate. Albumin is the main binding protein, both in health and in advanced stages of chronic kidney disease. Modeling suggests that albumin contains two binding sites for both toxins, a single high affinity binding site and a second low affinity binding site. The high affinity binding site accounts for at least 90% of overall binding. Competition for this binding site could be used to augment free solute concentrations during dialysis, thus improving epuration.

Journal ArticleDOI
TL;DR: Human serum albumin is useful in detoxification reactions, for activating prodrugs, and for binding and activating drug conjugates, and can be used to construct smart nanotubes with enzymatic properties useful for biomedical applications.

Journal ArticleDOI
TL;DR: GA is a ketoamine formed via a non-enzymatic glycation reaction of serum albumin and it reflects mean glycemia over two to three weeks and is useful as part of a routine examination to screen for both diabetes and atherosclerosis.

Journal ArticleDOI
17 Jul 2013-DARU
TL;DR: Albumin conjugated PLGA nanoparticles may represent a promising drug delivery system in cancer therapy and results in more cytotoxicity against tumor cell lines compared with free docetaxel and unconjugated PL GA nanoparticles.
Abstract: Background: Poly lactic-co-glycolic acid (PLGA) based nanoparticles are considered to be a promising drug carrier in tumor targeting but suffer from the high level of opsonization by reticuloendothelial system due to their hydrophobic structure. As a result surface modification of these nanoparticles has been widely studied as an essential step in their development. Among various surface modifications, human serum albumin (HSA) possesses advantages including small size, hydrophilic surface and accumulation in leaky vasculature of tumors through passive targeting and a probable active transport into tumor tissues. Methods: PLGA nanoparticles of docetaxel were prepared by emulsification evaporation method and were surface conjugated with human serum albumin. Fourier transform infrared spectrum was used to confirm the conjugation reaction where nuclear magnetic resonance was utilized for conjugation ratio determination. In addition, transmission electron microscopy showed two different contrast media in conjugated nanoparticles. Furthermore, cytotoxicity of free docetaxel, unconjugated and conjugated PLGA nanoparticles was studied in HepG2 cells. Results: Size, zeta potential and drug loading of PLGA nanoparticles were about 199 nm, �11.07 mV, and 4%, respectively where size, zeta potential and drug loading of conjugated nanoparticles were found to be 204 nm, �5.6 mV and 3.6% respectively. Conjugated nanoparticles represented a three-phasic release pattern with a 20% burst effect for docetaxel on the first day. Cytotoxicity experiment showed that the IC50 of HSA conjugated PLGA nanoparticles (5.4 μg) was significantly lower than both free docetaxel (20.2 μg) and unconjugated PLGA nanoparticles (6.2 μg). Conclusion: In conclusion surface modification of PLGA nanoparticles through HSA conjugation results in more cytotoxicity against tumor cell lines compared with free docetaxel and unconjugated PLGA nanoparticles. Albumin conjugated PLGA nanoparticles may represent a promising drug delivery system in cancer therapy.

Journal ArticleDOI
TL;DR: Serum albumin level within 24 h of admission is a good prognostic marker in community-acquired pneumonia and Physicians should consider albuminlevel when evaluating the severity of illness in patients with CAP.

Journal ArticleDOI
TL;DR: Synergistic efflux was obtained when LPDS was incubated with cells and LDL, and a synergistic effect was also obtained when RBC was used as the sink and albumin as shuttle.

Journal ArticleDOI
TL;DR: The results demonstrate that multikinase inhibitor loaded nanoparticles are interesting nanomedicines for the treatment of EGFR-positive cancers.

Journal ArticleDOI
TL;DR: Forescence resonance energy transfer (FRET) analysis proved high probability of energy transfer from Trp residue to the drug molecule and alterations of protein secondary structure in the presence of gemcitabine were assessed by CD UV-vis and FT-IR spectroscopy.

Journal ArticleDOI
05 Jul 2013-PLOS ONE
TL;DR: This study suggests that different regions of the brain are equally permeable to LMW inert dyes like the EBD, but are markedly different in permeability to HMW proteins such as EBD-labelled serum albumin.
Abstract: The Evans blue dye (EBD; 961 Da) and the sodium fluorescein dye (NaF; 376 Da) are commonly used inert tracers in blood-brain barrier (BBB) research. They are both highly charged low molecular weight (LMW) tracers with similar lipophobic profiles. Nevertheless, the EBD binds to serum albumin (69,000 Da) to become a high molecular weight (HMW) protein tracer when injected into the circulation, whereas the NaF remains an unbound small molecule in the circulation. In this study, rats were injected with equal doses of either EBD or NaF to monitor their blood and tissue distribution. The EBD was largely confined to the circulation with little accumulation in the peripheral organ and even less accumulation in the central tissue, whereas the NaF distributed more evenly between the blood and the peripheral organ but was also largely excluded from the central tissue. Importantly, the EBD crossed the BBB most effectively at the prefrontal cortex and the cerebellum, and most poorly at the striatum. In marked contrast, the NaF was evenly distributed throughout the brain. Finally, the EBD exhibited this same peculiar tissue distribution profile when administered by either bolus injection or slow infusion. Our study suggests that different regions of the brain are equally permeable to LMW inert dyes like the NaF, but are markedly different in permeability to HMW proteins such as EBD-labelled serum albumin.

Journal ArticleDOI
TL;DR: IFA might be a new promising anti-glycation agent for the prevention of diabetic complications via inhibition of AGEs formation and oxidation-dependent protein damage.
Abstract: The inhibitory activity of isoferulic acid (IFA) on fructose- and glucose-mediated protein glycation and oxidation of bovine serum albumin (BSA) was investigated. Our data showed that IFA (1.25–5 mM) inhibited the formation of fluorescent advanced glycation end products (AGEs) and non-fluorescent AGE [Ne-(carboxymethyl) lysine: CML], as well as the level of fructosamine. IFA also prevented protein oxidation of BSA indicated by decreasing protein carbonyl formation and protein thiol modification. Furthermore, IFA suppressed the formation of β-cross amyloid structures of BSA. Therefore, IFA might be a new promising anti-glycation agent for the prevention of diabetic complications via inhibition of AGEs formation and oxidation-dependent protein damage.

Journal ArticleDOI
TL;DR: Serum fructosamine and glycated albumin are risk factors for mortality and morbidity in hemodialysis patients and higher values of both markers were associated with trends toward a higher risk of hospitalization with sepsis.
Abstract: OBJECTIVE Assays for serum total glycated proteins (fructosamine) and the more specific glycated albumin may be useful indicators of hyperglycemia in dialysis patients, either as substitutes or adjuncts to standard markers such as hemoglobin A 1c , as they are not affected by erythrocyte turnover. However, their relationship with long-term outcomes in dialysis patients is not well described. RESEARCH DESIGN AND METHODS We measured fructosamine and glycated albumin in baseline samples from 503 incident hemodialysis participants of a national prospective cohort study, with enrollment from 1995–1998 and median follow-up of 3.5 years. Outcomes were all-cause and cardiovascular disease (CVD) mortality and morbidity (first CVD event and first sepsis hospitalization) analyzed using Cox regression adjusted for demographic and clinical characteristics, and comorbidities. RESULTS Mean age was 58 years, 64% were white, 54% were male, and 57% had diabetes. There were 354 deaths (159 from CVD), 302 CVD events, and 118 sepsis hospitalizations over follow-up. Both fructosamine and glycated albumin were associated with all-cause mortality; adjusted HR per doubling of the biomarker was 1.96 (95% CI 1.38–2.79) for fructosamine and 1.40 (1.09–1.80) for glycated albumin. Both markers were also associated with CVD mortality [fructosamine 2.13 (1.28–3.54); glycated albumin 1.55 (1.09–2.21)]. Higher values of both markers were associated with trends toward a higher risk of hospitalization with sepsis [fructosamine 1.75 (1.01–3.02); glycated albumin 1.39 (0.94–2.06)]. CONCLUSIONS Serum fructosamine and glycated albumin are risk factors for mortality and morbidity in hemodialysis patients.

Journal ArticleDOI
TL;DR: Structural details of the ligand binding functions of HSA to ligands such as warfarin, digoxin, halothane anesthetics, nitric oxide, bilirubin, free fatty acids, etc, can be used to develop a model to better understand protein-drug interactions, aid in the development of new drugs with improved pharmacokinetic effects, and ultimately beUsed to improve the quality of healthcare.

Journal ArticleDOI
01 Mar 2013-Urology
TL;DR: In this paper, the authors evaluated preoperative albumin levels as a marker for comparing survival outcomes after cystectomy in patients with bladder cancer, and found that patients with low pre-operative albumin had an increased overall mortality and cancer-specific mortality risk than those with normal albumin level.

Journal ArticleDOI
28 Jan 2013-PLOS ONE
TL;DR: An additional mechanism by which anti-proteinuric therapies are beneficial in the treatment of glomerular diseases may be a reduction in injury to the podocyte by albumin, which is strongly associated with progression of chronic kidney disease.
Abstract: The presence of albuminuria is strongly associated with progression of chronic kidney disease. While albuminuria has been shown to injure renal proximal tubular cells, the effects of albumin on podocytes have been less well studied. We have addressed the hypothesis that exposure of podocytes to albumin initiates an injury response. We studied transformed human-urine derived podocytes-like epithelial cells (HUPECS, or podocytes). Upon differentiation, these cells retain certain characteristics of differentiated podocytes, including expression of synaptopodin, CD2AP, and nestin. We exposed podocytes to recombinant human albumin, which lacks lipids and proteins that bind serum albumin; this reagent allowed a direct examination of the effects of albumin. Podocytes endocytosed fluoresceinated albumin and this process was inhibited at 4°C, suggesting an energy-dependent process. Exposure to albumin at concentrations of 5 and 10 mg/ml was associated with increased cell death in a dose-dependent manner. The mechanism of cell death may involve apoptosis, as caspase 3/7 were activated and the pan-caspase inhibitor z-VAD reduced cell death. Albumin exposure also increased nuclear factor (NF)-κB activation and increased transcription and release of interleukin (IL-) 1β, tumor necrosis factor (TNF), and IL-6. We extended these findings to an in vivo model. Glomeruli isolated from mice with nephrotic syndrome also had increased expression of IL-1β and TNF RNA. These data suggest that while podocyte injury begets albuminuria, albumin in the glomerular ultrafiltrate may also beget podocyte injury. Thus, an additional mechanism by which anti-proteinuric therapies are beneficial in the treatment of glomerular diseases may be a reduction in injury to the podocyte by albumin.

Journal ArticleDOI
TL;DR: Two crystal structures of the complexes of equine and bovine serum albumins with 3,5-diiodosalicylic acid (DIS) are presented and results with the HSA binding ability of DIS and other structurally similar ligands are compared.

Journal ArticleDOI
TL;DR: Cationic bovine serum albumin-conjugated tanshinone IIA PEGylated nanoparticles possessed remarkable neuroprotective effects on ischemic stroke through modulation of inflammatory cascades and neuronal signal pathways involved in cerebral ischemia.