Showing papers on "Serum albumin published in 2002"
TL;DR: Fluorescence emission spectra of serum albumin in the presence of MMI or PTU, recorded at the excitation wavelengths 280 and 295 nm, clearly show that the studied drugs act as quenchers.
789 citations
TL;DR: A series of peptides having the core sequence DICLPRWGCLW that specifically bind serum albumin from multiple species with high affinity are identified, suggesting a novel and generic method for improving the pharmacokinetic properties of rapidly cleared proteins.
754 citations
TL;DR: The results suggest that Nigella sativa oil may play a role against the alterations caused by S. mansoni infection, an effect which may be induced partly by improving the immunological host system and to some extent with its antioxidant effect.
330 citations
TL;DR: The physiological role of albumin in the human body and the pharmacological consequences of drug-albumin binding are reviewed, and the structure and the properties of the protein binding sites, as studied by different methodologies are focused on.
Abstract: Human serum albumin (HSA) plays a fundamental role in the transport of drugs, metabolites, and endogenous ligands. Binding to HSA controls the free, active concentration of a drug, provides a reservoir for a long duration of action, and ultimately affects drug absorption, metabolism, distribution and excretion. The free concentration of a drug can also be affected by interaction with co-administered drugs or by pathological conditions that can modify to a significant extent the binding properties of the carrier, resulting in important clinical impacts for drugs that have a relatively narrow therapeutic index. This manuscript will review the physiological role of albumin in the human body and the pharmacological consequences of drug-albumin binding, and then focus on the structure and the properties of the protein binding sites, as studied by different methodologies. Among these, biochromatography on immobilized albumin has been shown to be a rapid and effective tool for the characterization of albumin binding sites and their enantioselectivity, and for the study of the changes in the binding properties of the protein arising by interaction between different ligands. We will discuss the potential offered by the combined use of circular dichroism on the same protein/drug system in solution, not only for the determination of binding parameters and the detection of displacement phenomena, but also for the identification of conformational features underlying binding stereoselectivity. In particular, the essential role of these methodologies in the study of the enantioselective phenomena occurring in the HSA binding of chiral drugs will be addressed. The effect of reversible or covalent binding of drugs will also be discussed and examples of physiological relevance reported.
312 citations
TL;DR: Gene manipulation techniques open up the possibility of making recombinant human serum albumin (rHSA) or mutants with desirable therapeutic properties and for protein fusion products, as well as site-directed mutants of HSA can be tailor made depending on the application required.
Abstract: Gene manipulation techniques open up the possibility of making recombinant human serum albumin (rHSA) or mutants with desirable therapeutic properties and for protein fusion products. rHSA can serve as a carrier in synthetic heme protein, thus reversibly carrying oxygen. Myristoylation of insulin results in a prolonged half-life because of self aggregation and increased albumin binding. Preferential albumin uptake by tumor cells serves as the basis for albumin-anticancer drug conjugate formulation. Furthermore, drug targeting can be achieved by incorporating drugs into albumin microspheres whereas liver targeting can be achieved by conjugating drug with galactosylated or mannosylated albumin. Microspheres and nanoparticles of different sizes can, with or without drugs and/or radioisotopes, be used for drug delivery or diagnostic purposes. In vivo implantation of albumin fusion protein expressing cells encapsulated in HSA-alginate coated beads showed promising results compared to organoids in rats. Chimeric peptide strategy with cationized albumin as the transport can deliver drugs via receptor mediated transcytosis through the blood brain barrier. Gene bearing, albumin microbubbles containing ultrasound contrast agents can non-invasively deliver gene after destruction by ultrasound. Various site-directed mutants of HSA can be tailor made depending on the application required.
312 citations
TL;DR: Polyamidoamine dendrimers interaction with bovine serum albumin was studied and it was shown that the generation 4 has a greater impact on spectral properties of serumalbumin than generation 3.5.
279 citations
TL;DR: Kratz et al. as discussed by the authors proposed a macromolecular prodrug strategy for improved cancer chemotherapy based on two features: rapid and selective binding of thiol-reactive prodrugs to the cysteine-34 position of endogenous albumin after intravenous administration and release of the albumin-bound drug in the acidic environment at the tumor site due to the incorporation of an acidsensitive bond between the drug and the carrier.
Abstract: We have recently proposed a macromolecular prodrug strategy for improved cancer chemotherapy based on two features (Kratz, F.; et al. J. Med. Chem 2000, 43, 1253−1256.): (a) rapid and selective binding of thiol-reactive prodrugs to the cysteine-34 position of endogenous albumin after intravenous administration and (b) release of the albumin-bound drug in the acidic environment at the tumor site due to the incorporation of an acid-sensitive bond between the drug and the carrier. To investigate this therapeutic strategy in greater depth, four (maleinimidoalkanoyl)hydrazone derivatives of doxorubicin were synthesized differing in the length of the aliphatic spacer (1, −(CH2)2−; 2, −(CH2)3−; 3, −(CH2)5−; 4, −(CH2)7−). The albumin-binding doxorubicin prodrugs, especially the (6-maleimidocaproyl)hydrazone derivative of doxorubicin (3), are rapidly and selectively bound to the cysteine-34 position of endogenous albumin. 3 was distinctly superior to the parent compound doxorubicin in three animal tumor models (R...
274 citations
TL;DR: Within the range of albumin levels in hemodialysis patients, nutritional variables primarily affected albumin synthesis while inflammation caused hypoalbuminemia by increasing albumin FCR.
241 citations
TL;DR: This work has presented a review of the research on reactions of platinum(II) and (IV), gold(I) and(III), ruthenium(III) and rhodium( II) antitumoral compounds with serum albumin, and found that platinum and gold compounds are found to react with S-donors such as methionine and the Cys34 residues of albumin.
229 citations
TL;DR: Glycated albumin detected by the present method was significantly correlated with glycated album in detected by high-performance liquid-chromatographic (HPLC) method.
211 citations
TL;DR: Ochratoxin A (OTA), a fungal metabolite produced by several strains of Aspergillus and Penicillium, binds to serum albumin with high affinity only in the completely deprotonated form (dianion).
Abstract: Ochratoxin A (OTA), a fungal metabolite produced by several strains of Aspergillus and Penicillium, binds to serum albumin with high affinity only in the completely deprotonated form (dianion). The pKa of the phenolic group of OTA decreased by more than three units when it was bound to human serum albumin (HSA). Optical spectroscopy provided evidence that HSA has at least two binding sites for OTA, each being able to accommodate one dianion. These two sites were characterized by the binding constants of 5.2 × 106 and 1.0 × 105 M-1. The binding constant for the monoanion of OTA was estimated to be ∼103 M-1. Fluorescence polarization spectroscopy confirmed weak interaction of the monoanion with the protein in the F and E forms (pH 8) compared to the N form (pH ∼ 7). Fluorescence anisotropy decay of the dianion of OTA bound to HSA (36.6 ns) was much longer than its emission lifetime (5.2 ns) and was close to reported values for the rota...
TL;DR: Exposure to excess proteins in proximal tubular cells induces the formation of ROS, which is responsible for NF-kappaB activation and consequent induction of NF- kappaB-dependent inflammatory signals, according to real-time PCR data.
Abstract: Abnormal traffic of proteins through the glomerular capillary has an intrinsic toxicity that results in tubular dysfunction and interstitial inflammation. It has been previously shown that in porcine proximal tubular cells high concentrations of albumin activated NF-kappaB, which is responsible for the enhanced synthesis of the inflammatory chemokine RANTES. This study investigates whether reactive oxygen species (ROS) served as second messengers in protein overload-induced NF-kappaB activation. Human proximal tubular cells (HK-2) were incubated (5 to 60 min) with human albumin and IgG (1 to 30 mg/ml). Both proteins induced a rapid or significant increase in hydrogen peroxide (H(2)O(2)) production at 5 min and persisting at 60 min. This effect was dose-dependent. The contribution of H(2)O(2) in regulating NF-kappaB activation was evaluated by using the antioxidants dimethyl-thiourea and pyrrolidine dithiocarbamate in protein-overloaded HK-2 cells. Both agents, by preventing H(2)O(2) generation, induced human albumin or IgG inhibited NF-kappaB activation. Stimulation of HK-2 with exogenous H(2)O(2) resulted in the activation of a NF-kappaB subunit pattern similar to that obtained after protein challenge. Specific inhibitors of protein kinase C (PKC) activity significantly prevented H(2)O(2) production and consequent NF-kappaB activation, suggesting that ROS generation in HK-2 cells occurs downstream of PKC activation. Either antioxidants or PKC inhibitor almost completely abolished the upregulation of the monocyte chemoattractant protein-1 gene induced by excess albumin, as evaluated by real-time PCR, thus supporting a role for PKC and ROS as critical signals for the expression of NF-kappaB-dependent inflammatory genes. To identify the enzymatic sources responsible for the increased H(2)O(2) production, the effect of dyphenyleneiodonium, an inhibitor of the membrane NADP(H) oxidase, was studied, as was the effect of rotenone, which blocks complex I of the mitochondrial respiratory chain. It was found that both agents significantly reduced the exaggerated H(2)O(2) induced by protein overload. These data indicate that exposure to excess proteins in proximal tubular cells induces the formation of ROS, which are responsible for NF-kappaB activation and consequent induction of NF-kappaB-dependent inflammatory signals.
TL;DR: Lower serum albumin concentrations appear to be associated with an increased risk of coronary disease in both sexes and with all-cause mortality in women and could help along with traditional risk factors in identifying people at risk of MI.
Abstract: Background— Coronary disease remains the leading cause of death in the United States. The association between serum albumin and cardiovascular disease remains controversial. We used data collected prospectively from participants of the Framingham Offspring Study to assess whether a lower concentration of serum albumin was associated with an increased risk of myocardial infarction (MI) and all-cause mortality. Methods and Results— During 21.9 years of mean follow-up, 280 cases of MI occurred. From the highest to the lowest tertile of serum albumin, crude incidence rates of MI were 26.7, 46.7, and 67.8 cases per 10 000 person-years, respectively, for men and 5.9, 15.0, and 16.8 cases per 10 000 person-years, respectively, for women. In a Mantel-Haenszel method adjusting for age, total cholesterol, and hypertension, lower serum albumin was associated with an increased risk of MI in both sexes. From the highest to the lowest tertile of albumin, the adjusted hazard ratios (95% CI) of MI were 1.0 (reference), 1...
TL;DR: In this article, Bovine serum albumin (BSA) was modified by covalent attachment of chlorogenic acid using different concentrations at pH 9. The structural changes were studied using circular dichroism, differential scanning calorimetry (DSC), intrinsic fluorescence, and binding of anilinonaphthalenesulfonic acid.
TL;DR: The first unequivocal identification of the lysine-arginine cross-links glucosepane 5, DOGDIC 6, MODIC 7, and GODIC 8 in human material is reported on, appearing predestined as markers for pathophysiological processes.
TL;DR: It is the FFAs bound to albumin, rather than albumin itself, which cause severe tubulointerstitial damage by being reabsorbed into the proximal tubule, the first in vivo observation in which FFAs have caused severe Tubulointerstitial injury.
TL;DR: It is shown that homocysteine is a protein amino acid in humans, bound by amide or peptide linkages (Hcy-N-protein), which is present in human hemoglobin, serum albumin, and γ-globulins.
TL;DR: In this article, the interactions between terazosin and bovine serum albumin (BSA) were studied by spectrofluorimetry, and the binding constants of BSA were measured at different temperatures.
TL;DR: From the results of this study it can be concluded that Zn deficiency exerts numerous alterations in the studied biochemical parameters, protein pattern, and increased lipid peroxidation.
TL;DR: Results suggest that in addition to the lipid-lowering effect, simvastatin had an antiinflammatory effect in HD patients and may have a beneficial effect on cardiovascular disease, in part because it alleviates inflammation.
TL;DR: Amarasmus, the classification for chronic starvation and malnutrition, is defined as a wasted, cachetic physical appearance with intact serum albumin levels as mentioned in this paper, which is an indicator of poor nutritional status and inadequate protein intake.
TL;DR: The early and advanced glycation adduct contents of these proteins were investigated using the 6-aminoquinolyl-N-hydroxysuccinimidyl-carbamate (AQC) chromatographic assay of enzymic hydrolysates and most AGEs in albumin glycated minimally by methylglyoxal and glucose were identified.
Abstract: Glycation of proteins leads to the formation of advanced glycation endproducts (AGEs) of diverse molecular structure and biological function. Serum albumin derivatives modified to minimal and high extents by methylglyoxal and glucose in vitro have been used in many studies as model AGE proteins. The early and advanced glycation adduct contents of these proteins were investigated using the 6-aminoquinolyl-N-hydroxysuccinimidyl-carbamate (AQC) chromatographic assay of enzymic hydrolysates. AGEs derived from methylglyoxal, glyoxal and 3-deoxyglucosone, the hydroimidazolones N(delta)-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1), N(delta)-(5-hydro-4-imidazolon-2-yl)ornithine (G-H1) and N(delta)-[5-(2,3,4-trihydroxybutyl)-5-hydro-4-imidazolon-2-yl]ornithine (3DG-H1), bis(lysyl)imidazolium cross-links methylglyoxal-derived lysine dimer (MOLD), glyoxal-derived lysine dimer (GOLD), 3-deoxyglucosone-derived lysine dimer (DOLD), monolysyl adducts N(epsilon)-(1-carboxyethyl)lysine (CEL), N(epsilon)-carboxymethyl-lysine (CML) and pyrraline, other AGEs, N(delta)-(4-carboxy-4,6-dimethyl-5,6-dihydroxy-1,4,5,6-tetrahydropyrimidin-2-yl)ornithine (THP), argpyrimidine and pentosidine, and fructosyl-lysine were determined. AGEs with intrinsic fluorescence (argpyrimidine and pentosidine) were assayed without derivatization. Human serum albumin (HSA) glycated minimally by methylglyoxal in vitro contained mainly MG-H1 with minor amounts of THP and argpyrimidine. Similar AGEs were found in prothrombin glycated minimally by methylglyoxal and in N(alpha)-t-butyloxycarbonyl-arginine incubated with methylglyoxal. HSA glycated highly by methylglyoxal contained mainly argpyrimidine, MG-H1 and THP, with minor amounts of CEL and MOLD. HSA glycated minimally by glucose in vitro contained mainly fructosyl-lysine and CML, with minor amounts of THP, MG-H1, G-H1, 3DG-H1, argpyrimidine and DOLD. HSA glycated highly by glucose contained these AGEs and pyrraline, and very high amounts ( approximately 8 mol/mol of protein) of fructosyl-lysine. Most AGEs in albumin glycated minimally by methylglyoxal and glucose were identified. Significant proportions of arginine and lysine-derived AGEs in albumin modified highly by methylglyoxal, and lysine-derived AGEs in albumin modified highly by glucose, remain to be identified.
TL;DR: Pediatric patients initiating dialysis with hypoalbuminemia are at a higher risk for death, and this finding persists after adjusting for glomerular causes for ESRD and other potential confounding variables.
TL;DR: The findings suggest that animal monoclonal antibodies specific for cow's milk proteins are able to recognize the major part of milk proteins from mammals bred in Mediterranean countries (sheep, goat, and buffalo); weak cross-reactivity was observed with milk proteins with mares and donkeys.
Abstract: Background Cross-reactivity between food allergens occurs when they share part of their amino acid sequence, or when their three-dimensional molecular structure causes them to have a similar capacity to bind specific antibodies. Objectives To review data from our laboratory on cross-reactivity between mammalian proteins (milk and meat allergens). Methods Studies used immunoelectrophoresis (sodium dodecyl sulfate-polyacrylamide gel electrophoresis/polyacrylamide gel electrophoresis and immunoblotting), and animal monoclonal antibodies. Results The findings suggest that animal monoclonal antibodies specific for cow's milk proteins are able to recognize the major part of milk proteins from mammals bred in Mediterranean countries (sheep, goat, and buffalo); weak cross-reactivity was observed with milk proteins from mares and donkeys. None of the antibodies used in our studies reacted with proteins from an exotic mammalian species: the camel. Similar cross-reactions were found with human circulating immunoglobulin E from children allergic to milk. With regard to beef allergy, monoclonal antibodies specific for bovine serum albumin cross-reacted only with ovine serum albumin, whereas the number of sera from allergic children able to recognize other mammalian serum albumins depended directly on the closeness of phylogenetic relationship between animal species and inversely on the percent identity with human serum albumin in the main epitopic sequence. Conclusion An area of heterogeneity between animal and human species in a critical amino acid sequence (epitope) of an allergen can determine the degree of immunogenic activity.
Patent•
08 Mar 2002
TL;DR: In this article, compositions comprising non-naturally occurring serum albumin binding moieties are described, together with methods of use thereof, e.g., for detecting or isolating serum bandit molecules in a solution, for blood circulation imaging, and for linking therapeutics or other molecules to albumin.
Abstract: Compositions comprising non-naturally occurring serum albumin binding moieties are described, together with methods of use thereof, e.g., for detecting or isolating serum albumin molecules in a solution, for blood circulation imaging, and for linking therapeutics or other molecules to albumin. Preferred serum albumin binding peptides having a high affinity for human serum albumin are particularly disclosed.
TL;DR: Results suggest that the hydrophobic phase formed by albumin serves as a major reservoir of NO⋅ and its reactive oxides and controls the dynamics of NO ⋅-dependant processes in the vasculature.
Abstract: Nitric oxide (NO⋅) is a short-lived physiological messenger. Its various biological activities can be preserved in a more stable form of S-nitrosothiols (RS-NO). Here we demonstrate that at physiological NO⋅ concentrations, plasma albumin becomes saturated with NO⋅ and accelerates formation of low-molecular-weight (LMW) RS-NO in vitro and in vivo. The mechanism involves micellar catalysis of NO⋅ oxidation in the albumin hydrophobic core and specific transfer of NO+ to LMW thiols. Albumin-mediated S-nitrosylation and its vasodilatory effect directly depend on the concentration of circulating LMW thiols. Results suggest that the hydrophobic phase formed by albumin serves as a major reservoir of NO⋅ and its reactive oxides and controls the dynamics of NO⋅-dependant processes in the vasculature.
TL;DR: In this article, the effects of bovine serum albumin (BSA) on TNFα-induced expression of adhesion molecules in cultured human aortic endothelial cells (HAEC) were investigated.
Abstract: Objective: Leukocyte adhesion to, and transmigration across, the vascular endothelium are critical initiating steps in inflammation and atherosclerosis. We hypothesized that albumin, the major plasma protein, acts as an anti-inflammatory agent towards endothelial cells. Methods and Results: To test the hypothesis, we studied the effects of bovine serum albumin (BSA) on TNFα-induced expression of adhesion molecules in cultured human aortic endothelial cells (HAEC). We found that incubation of HAEC for 16 h with BSA (0.5–5%, w/v) dose-dependently inhibited TNFα-induced mRNA and protein expression of vascular cell adhesion molecule-1 (VCAM-1), but not intercellular adhesion molecule-1 nor E-selectin. Yeast recombinant human serum albumin exerted similar inhibitory effects on VCAM-1 expression, whereas γ-globulin was ineffective. BSA also significantly inhibited TNFα-induced adhesion of monocytic THP-1 cells to HAEC in a dose-dependent manner. Furthermore, BSA strongly inhibited activation and nuclear translocation of the transcription factor, nuclear factor-κB (NF-κB). For example, the physiologically relevant concentration of 5% BSA inhibited NF-κB activation by 90±7%, VCAM-1 mRNA and protein expression by 81±4 and 80±13%, respectively, and THP-1 adhesion by 73±9% ( n = 3). The inhibitory effect of BSA on TNFα-induced VCAM-1 expression was not attenuated by inhibition of intracellular GSH synthesis. Conclusions: Our data show that physiological concentrations of albumin selectively inhibit TNFα-induced upregulation of VCAM-1 expression and monocyte adhesion, most likely by inhibiting NF-κB activation in a GSH-independent manner.
TL;DR: In this article, the authors examined whether subjects with autism showed changes in total serum protein (TSP) and the serum concentrations of albumin, α1 globulin, α2 globulin and β globulin.
Abstract: Background. Research on the biological pathophysiology of autism has found some evidence that immune alterations may play a role in the pathophysiology of that illness. As a consequence we expected to find that autism is accompanied by abnormalities in the pattern obtained in serum protein electrophoresis and in the serum immunoglobulin (Ig) and IgG subclass profile.Method. We examined whether subjects with autism showed changes in total serum protein (TSP) and the serum concentrations of albumin, α1 globulin, α2 globulin, β globulin and γ globulins, IgA, IgM and IgG and the IgG subclasses IgG1, IgG2, IgG3 and IgG4, compared with normal controls.Results. We found significantly increased concentrations of TSP in autistic subjects, which were attributable to increased serum concentrations of albumin and γ globulin. Serum IgG, IgG2 and IgG4 were also significantly raised. In autism there were significant and positive correlations between social problems and TSP and serum γ globulin and between withdrawal symptoms and TSP and serum albumin and IgG.Conclusions. The results suggest that autism is characterized by increased TSP, a unique pattern obtained in serum protein electrophoresis, i.e. increased serum albumin and IgG, and by a specific IgG subclass profile, i.e. increased serum IgG2 and IgG4. The increased serum concentrations of IgGs in autism may point towards an underlying autoimmune disorder and/or an enhanced susceptibility to infections resulting in chronic viral infections, whereas the IgG subclass skewing may reflect different cytokine-dependent influences on autoimmune B cells and their products.
TL;DR: Serum albumin and clinically based measures such as the Subjective Global Assessment (SGA) are two potential methods of assessing nutritional status in hospitalized older people but it is not clear whether they measure similar or different clinical constructs.
Abstract: OBJECTIVES:
Malnutrition is common in hospitalized older people, and some have advocated routine nutritional screening. Serum albumin and clinically based measures such as the Subjective Global Assessment (SGA) are two potential methods of assessing nutritional status in hospitalized older people. Although both measures are strongly associated with prognosis, it is not clear whether they measure similar or different clinical constructs. Our goal was to assess the degree of clinical concordance between these measures.
DESIGN:
Cross-sectional study.
SETTING:
The inpatient medical service of a university teaching hospital.
PARTICIPANTS:
Three hundred eleven older (aged ≥70) patients.
MEASUREMENTS:
We independently measured serum albumin and performed the SGA on 311 older medical patients (aged ≥70) shortly after hospital admission. The SGA classified patients as well nourished, moderately malnourished (generally 5% weight loss with mild examination findings), or severely malnourished (generally>10% weight loss with marked findings) based on findings from a directed history and examination. We compared the distribution of clinical rating in patients with differing albumin levels and examined diagnostic test characteristics of albumin as a predictor of malnutrition as diagnosed on clinical examination.
RESULTS:
The mean age of subjects was 79.9; 64% were women, 42% were African American. Discordance between albumin and the SGA was common. For example, 38% of patients with albumin levels of 4.0 g/dL or higher were at least moderately malnourished on the SGA, whereas 28% of patients with albumin levels lower than 3.0 g/dL were rated as well nourished. No choice of albumin level was associated with simultaneously acceptable sensitivity and specificity as a predictor of SGA ratings. The area under the receiver operating characteristic curve for albumin level as a predictor of SGA rating was 0.58, suggesting that the ability of either measure to predict the other measure is only marginally better than chance.
CONCLUSIONS:
Albumin levels and clinical assessments, two possible measures of nutritional status in hospitalized older people, are often discordant. To some extent, this reflects limitations in both measures as markers of nutritional status. However, it also demonstrates that, in this population, albumin and clinical assessments of nutritional status reflect fundamentally different clinical processes. J Am Geriatr Soc 50:631–637, 2002.
TL;DR: It is demonstrated for the first time, that glycated serum albumin, not glucose, increases VEGF production in HMC, and this results confirm clinical data that the continuous exposure of the peritoneal membrane to glucose-based dialysis solutions is an important stimulus for V EGF expression.