Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0393754 (HSA)
 2,996 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The binding of cicletanine to human serum, isolated proteins and red blood cells was studied in vitro by equilibrium dialysis. Our results show this drug is highly bound to serum (97.3%) at therapeutic levels. No saturation to the binding sites was seen. Human serum albumin was shown to mainly responsible for this binding (93.5%) with a saturable process characterized by one binding site with a moderate affinity (K = 75800 M-1) and a non saturable process with a low total affinity (nK = 6400 M-1). Like many basic lipophilic drugs, cicletanine showed a saturable binding to alpha-1-acid glycoprotein with one site and a moderate affinity (K = 38,800 M-1). Its binding to lipoproteins and red blood cells was weak and non saturable. Over the range of therapeutic concentrations, the unbound fraction in blood remains constant (3.6%). Moreover, interactions were studied using bilirubin and non esterified fatty acids at pathological concentrations and these endogenous compounds did not alter cicletanine binding human serum or to human serum albumin likewise cicletanine shared the diazepam-site on HSA but no inhibition could take place between cicletanine and the drugs sharing the same binding site in serum at therapeutic levels.
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PMID:Cicletanine binding to human plasma proteins and erythrocytes, a particular HSA-drug interaction. 321 Sep 2

Fibronectin (Fn) is a normal plasma and extracellular matrix glycoprotein that is thought to be important in reticuloendothelial system function as well as in promoting adhesion of various cell types to basement membranes and to each other. Plasma Fn levels are depressed following almost any type of trauma. It opsonizes circulating tissue debris for removal by the fixed cells of the reticuloendothelial system. It has been assumed but not proven that Fn also opsonizes tissue debris at the site of the injury for subsequent phagocytosis by tissue macrophages. In this study, rats were given intracardiac injections of Fn coupled with fluorescence isothiocyanate (Fn-FITC) and human serum albumin-rhodamine isothiocyanate (HSA-RITC). Abdominal Rebuck skin windows were then prepared. Within 24 hours, debris at the sites of injury were observed to be coated with Fn-FITC but not HSA-RITC. This Fn-labeled debris was subsequently ingested by macrophages at the site. No macrophages were found that had taken up HSA-RITC. Thus, Fn is seen to coat tissue debris and effete cells within the wound, and the coated material is subsequently removed by tissue macrophages.
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PMID:Tissue debris at the injury site is coated by plasma fibronectin and subsequently removed by tissue macrophages. 334 3

The serum concentrations of alpha-1-acid glycoprotein (AAG), albumin (HSA), and non-esterified fatty acids (NEFA), and the serum binding of indapamide were measured in four groups of individuals: control (healthy) subjects (N = 24), patients with inflammatory syndrome (N = 28), with hepatic (N = 20) and renal (N = 27) insufficiency. Indapamide serum binding was increased in patients with inflammatory syndrome (82.2 +/- 3.4%, P less than .001), decreased in patients with hepatic insufficiency (72.3 +/- 5.9%, P less than .001) and unchanged in patients with renal insufficiency (77.7 +/- 2.8%) as compared with controls (78.2 +/- 3.1%). A multivariate analysis indicated that these changes were mainly related to concomitant changes in AAG concentration (that explained 63% of intersubject variability in bound/free binding ratio), and to a lesser extent to HSA (that explained only 4% of the variability in the binding). These data show that the free fraction of the acidic drug indapamide in serum is affected by pathologic conditions in which changes in AAG concentration occur and that, unexpectedly, HSA plays a negligible role in the binding.
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PMID:Serum binding of indapamide in health and disease: primary role of alpha 1-acid glycoprotein. 339 44

The protein binding of carbamazepine (CBZ) in vitro was assessed in sera from 47 patients with various diseases known to alter alpha 1-acid glycoprotein (AAG) concentration and from 20 drug-free normal control subjects. In the patient group, AAG and albumin (HSA) concentrations ranged from 6 to 74 mumol/l and from 377 to 652 mumol/l, respectively; in the controls, protein concentrations were less variable, ranging from 11 to 26 mumol/l for AAG and from 623 to 754 mumol/l for HSA. In both the patient and the combined patient and control groups, free CBZ fractions were inversely correlated with the serum AAG concentration (r = -0.62). No significant relationship could be found between the free CBZ fraction and the serum HSA concentration. The free CBZ fraction was moderately but significantly decreased in patients with AAG levels above 26 mumol/l (the highest value found in controls) as compared either to patients with a normal AAG concentration or to control subjects (19 +/- 5% vs 23 +/- 4% and 23 +/- 2%), despite the finding of a higher HSA concentration in the control group. The data confirm AAG as an important determinant of interindividual variability in serum CBZ binding.
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PMID:Altered serum protein binding of carbamazepine in disease states associated with an increased alpha 1-acid glycoprotein concentration. 378 Aug 33

The relationship between the serum protein binding of carbamazepine (CBZ) and carbamazepine-10,11 epoxide (CBZ-E) and the concentration of alpha 1-acid glycoprotein (AAG) and albumin (HSA) was examined in 39 CBZ-treated epileptic children aged 4 months to 12 years. A significant inverse correlation was found between the free fraction of both compounds and serum AAG, even though changes in AAG concentration explained only part of the variation in binding. No correlation was found between the free fraction of CBZ and CBZ-E and HSA, probably due to the small intersubject variation in HSA concentration. In vitro experiments showed that both CBZ and CBZ-E were bound to HSA and to a lesser extent to AAG. At equivalent HSA concentrations, the binding of CBZ and its metabolite increased proportionately with increasing AAG concentration within the range occurring clinically.
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PMID:Alpha 1-acid glycoprotein concentration and serum protein binding of carbamazepine and carbamazepine-10,11 epoxide in children with epilepsy. 407 20

The uptake and degradation of a mannose-terminated glycoprotein, yeast invertase, in char (Salmo alpinus L.) tissue was studied after intravenously injection of the 125I-labelled protein. 125I-labelled formaldehyde-treated human serum albumin (fHSA) and native HSA was also injected for comparison. Labelled invertase was rapidly cleared from blood and at about the same rate as labelled fHSA (at 8 degrees C). Approximately 50% of the initial concentration remained in blood 15 min after the injection of the ligands. Acid soluble degradation products appeared in the circulation about 60 min after the injection of the proteins. 125I-labelled invertase was recovered in the liver, pronephros and kidney. The clearance of labelled invertase from blood and the uptake in the organs were inhibited by co-injection of excess unlabelled invertase. fHSA was taken up in the pronephros and kidney tissue, while HSA was not taken up in any organs. In vitro degradation of the labelled ligands was studied in isolated pronephros cells, which had taken up the proteins in vivo. The degradation of invertase in isolated cells was partly inhibited by ammonium chloride. Ammonium chloride and chloroquine inhibited degradation of fHSA, but not leupeptin. These results together suggest that invertase and fHSA were taken up in the organs described by the receptor-mediated endocytosis. The degradation was partly or wholly lysosomal.
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PMID:Endocytosis of a mannose-terminated glycoprotein and formaldehyde-treated human serum albumin in liver and kidney cells from fish (Salmo alpinus L.). 650 Jan 36

Binding of naloxone hydrochloride was determined at 37 degrees C, by equilibrium dialysis against 0.067 M phosphate buffer, pH 7.4, in plasma obtained from 18 healthy adults, and 18 samples of umbilical cord venous (foetal) plasma. The percentage free fraction (% free) in plasma was independent of naloxone concentration (9 ng/ml to 2.5 micrograms/ml). Percent free naloxone in adult (means = 54.0) was lower (p less than 0.01) than in foetal (means = 61.5) plasma. In buffered solutions of purified HSA, %free naloxone (means = 68.7) was independent of HSA concentration over the range 3.0 g/dl to 5.5 g/dl. Adult plasma concentrations of alpha 1-acid glycoprotein (alpha 1-AGP) and beta-lipoprotein were higher (p less than 0.01) than foetal concentrations. Furthermore %free naloxone in foetal plasma decreased with the in-vitro addition of purified alpha 1-AGP. It is suggested that qualitative differences in adult and foetal albumin and quantitative differences in plasma levels of alpha 1-AGP and perhaps beta-lipoprotein are responsible for naloxone plasma binding differences between adults and the newborn.
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PMID:Naloxone protein binding in adult and foetal plasma. 651 54

Human migration inhibitory factor (MIF), obtained from supernatants of peripheral blood mononuclear cells stimulated with concanavalin A, was analyzed by gel filtration, isoelectrofocusing, and CsCl density gradient centrifugation. A distinct pattern of heterogeneity was determined on the basis of its harvesting time and biochemical criteria. Supernatants from cells cultured for 1 day contained a single peak of MIF activity with an isoelectric point of 4.3 to 5.2, an apparent m.w. of 23,000, and a density of 1.314 g/ml, the same as the density of the marker protein, 125I-HSA (1st day pH 5-MIF). Furthermore, this species of human MIF was sensitive to treatment with trypsin, strongly suggesting its being a protein, but not to treatment with neuraminidase and corresponds therefore to guinea pig pH 5-MIF. However, when 2nd day supernatants were analyzed under the same conditions, 2 MIF species were found. One species with an isoelectric point of 2.4 to 3.3 had an apparent m.w. of 65,000 (2nd day 3-MIF). The other species with an isoelectric point of 4.3 to 5.6 had an apparent m.w. of 23-43,000 (2nd day pH 5-MIF). Upon centrifugation in CsCl density gradients, the density (rho 25 of 1.314 to 1.414 g/ml) of both species was found to be greater than that of the pure protein, 125I-HSA. In addition, both species were chymotrypsin and neuraminidase sensitive but not trypsin sensitive, further suggesting their glycoprotein nature.
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PMID:Studies on human migration inhibitory factor: characterization of three molecular species. 701 40

In healthy male subjects (n = 12) phencyclidine (PCP) free fraction was 22.0 +/- 2.8 % (mean +/- SD). In male patients with mild to moderate alcoholic liver disease (n = 16) free fraction (23.0 +/- 3.4%) was of the same order as in healthy subjects although age and the concentrations of albumin, bilirubin, and high-density lipoproteins were different (P less than 0.05). Free fraction (76.2 /+- 0.06%) in fatty acid free human serum albumin (HSA, 4.4 gm/dl) was far greater than in plasma. Both the increased binding of PCP in plasma over HSA and the lack of a difference in PCP binding between normals and patients was associated with alpha 1-acid glycoprotein (alpha 1-AGP). This protein is an acute-phase reactant that binds cationic drugs and rises nonspecifically in a variety of diseases. Free fraction of PCP in alpha 1-AGP (75 mg/dl) was 36.4 +/- 1.7%. Half of the variance in PCP binding can be accounted for (r = 0.67, P less than 0.01) from percentage of free PCP = 39.24 - 2.18 (albumin) - 0.094 (alpha 1-AGP). Male rats (n = 14, weight = 251 +/- 7 gm) were alternatively assigned to pretreatment with either saline or alpha 1-AGP (11.6 mg) by cardiac puncture. PCP brain concentrations were reduced (11%, P less than 0.05) in the protein-treated group 5 min after cardiac 3H-PCP (0.17 mg) administration, demonstrating that increased plasma protein binding can reduce free drug concentration during the distribution phase and, thereby, the rate and extent of drug distribution.
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PMID:Plasma protein binding of phencyclidine. 705 8

The molecular and cellular parameters of the transport of IgA immune complexes (IgA-IC) from the circulation to the bile in vivo were studied in mice. Polymeric MOPC 315 IgA was effective in the transport of 125I-DNP-HSA into the bile, whereas complexes containing monomeric IgA were not transported. The transport to IgA-IC could be blocked by excess from IgA of different antigen specificity, but not by IgG or IgM. Hepatobiliary transport did not appear to involve the galactose- or mannose-specific glycoprotein receptors of the liver. No differences in IgA-IC transport, relative to controls, could be seen in mice that had been treated with cobra venom factor or whose mononuclear phagocytic system had been blockaded with colloidal carbon. These data suggested that the hepatobiliary transport of IgA-IC proceeds by a mechanism similar to the selective transport of free polymeric IgA through the hepatocyte.
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PMID:Hepatobiliary transport of IgA immune complexes: molecular and cellular aspects. 706 58


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