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Results for “Plasma Protein Binding Capacity”

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PubMed1984

Brain uptake of a food dye, erythrosin B, prevented by plasma protein binding.

Although food colors have been held responsible for several behavioral disorders and do affect neuronal function when directly applied, there is no information on whether significant quantities of the dyes appear in the brain after consumption or parenteral administration. [14C]erythrosin B was administered directly into the circulation of mature rats and radioactivity was measured thereafter in brain regions at several times. Although insignificant parenchymal radioactivity was detected in brains perfused with dye in whole blood, significant concentrations of [14C]erythrosin B were detected in all brain regions when perfused with protein-free Ringers, as predicted from the octanol-water partition coefficient of the dye. Thus, significant brain uptake of intravascular dye is normally prevented by its binding to plasma protein (greater than 99% bound) and by the blood-brain barrier impermeability to the dye-protein complex. Sensitivity to food dyes such as erythrosin B in some individuals may reflect altered plasma protein binding capacity, which can vary with age and disease.

Animals↗
PubMed1990

99mTc-labelled trimethylmonoiodo-IDA: a new radiopharmaceutical for hepatobiliary imaging.

A new radiopharmaceutical, 99mTc-3-iodo-2,4,6-trimethylphenylcarbamoylmethyl iminodiacetic acid (99mTc-trimethylmonoiodo-IDA) was prepared and evaluated for hepatobiliary scintigraphy. The new agent has less plasma protein binding capacity and greater lipophilicity as compared to that of di-isopropyl-IDA. Hepatobiliary specificity, a short transit time and a high gall bladder-to-liver ratio of the new agent were evident from tissue distribution data in mice. Blood tmax and clearance t1/2 of the radiopharmaceutical were observed at 2 and 3.5 min respectively. The hepatic peak-time tmax (5 min) and release time t1/2 (12.75 min) and release t1/2 (25.00 min) suggest the suitability of this agent for hepatobiliary imaging. Results of hepatobiliary scintigraphy in rabbits have further confirmed the above view.

Animals↗
PubMed1998

Estrogen and estrogen-androgen replacement in postmenopausal women dissatisfied with estrogen-only therapy. Sexual behavior and neuroendocrine responses.

OBJECTIVE: To investigate the efficacy of esterified estrogens alone and combined with oral androgen on sexual function and menopausal symptoms in postmenopausal women. STUDY DESIGN: Twenty postmenopausal women dissatisfied with their estrogen or estrogen-progestin therapy volunteered to enter a double-blind, randomized trial in which they received either oral esterified estrogens or esterified estrogens + androgen for eight weeks after a single-blind, placebo, lead-in period. Sexual function was assessed with a questionnaire used in the Yale midlife survey, and plasma levels of estradiol, estrone, sex hormone binding globulin (SHBG) and beta-endorphin were measured at two- to four-week intervals. RESULTS: Estrogen-androgen therapy significantly improved sexual sensation and desire after four and eight weeks of double-blind treatment in comparison to previous estrogen therapy and postplacebo baseline assessments. Plasma levels of estradiol and estrone increased significantly in all patients as compared to the postplacebo baseline and decreased in comparison to circulating estrogen concentrations on previous therapy. Relative proportions of free and bound steroid hormone exhibited contrasting shifts during estrogen and estrogen-androgen therapy. SHBG increased in the estrogen group and decreased in the estrogen-androgen group, leading to lower amounts of free androgens during estrogen therapy and increased free androgen levels during estrogen-androgen therapy. Since proportions of free (bioavailable) ovarian steroids would correlate inversely with plasma protein binding capacity, the beneficial effects of oral estrogen-androgen therapy on sexual sensation and desire may be due either to the administered androgen or to the increased availability of endogenous and exogenous androgens, particularly in the central nervous system. CONCLUSION: Sexual desire, satisfaction and frequency in postmenopausal women taking hormonal therapy were improved significantly by combined estrogen-androgen therapy but not by estrogen or estrogen-progestin therapy. Sexual function improved with estrogen-androgen therapy even though circulating estrogen levels were lower than those measured during previous estrogen therapy. This leads to the conclusion that androgens play a pivotal role in sexual function but that estrogens are not a significant factor determining levels of sexual drive and enjoyment.

Double-Blind Method↗
PubMed1975

Plasma protein binding of carbamazepine.

The binding of carbamazepine to the proteins of human plasma has been studied using ultrafiltration techniques. In vitro studies at 37 degrees C showed the relation between concentration of unbound drug and total drug to be linear through the range of total concentration of 5 to 50 mug/ml. The per cent unbound drug increased slightly as concentration increased. There was little difference between the extent of binding at 4 degrees C and 20 degrees C, but more carbamazepine was unbound at 37 degrees C. Under in vitro conditions, 6 other anticonvulsants, and aspirin, were tested individually, each at high therapeutic or toxic concentration, and shown not to displace carbamazepine from plasma proteins to a significant degree. The extent of binding of carbamazepine in vivo was determined in a total of 54 plasma samples collected from treated patients; 26.9 plus or minus SD 9.4 percent of the drug was unbound. In blood samples from 23 of these patients, the red cell concentration of carbamazepine averaged 38.3 plus or minus SD 17.9 percent of the plasma concentration. The effects of hepatic and renal diseases on the carbamazepine binding capacity of plasma proteins were assessed by comparing the binding capacity of plasma from disease persons with that from normal subjects. There was no significant difference in binding capacity between plasma from patients with renal disease and that from normal subjects. However, the plasma from patients with hepatic disease bound a slightly lower percentage of carbamazepine than did normal plasma (p smaller than 0.05). This alteration did not correlate with changes in any of 15 biochemical parameters measured in these patients. The clinical significance of these results is discussed.

Adolescent↗
PubMed1977

[Binding capacity of some drugs to plasma proteins of newborns in comparison with adults (author's transl)].

Comparative studies on binding capacity of some drugs to plasma proteins of newborns and adults were carried out. Plasma from the newborn and adult rabbits as well as human from 4 sources: a) from healthy adults, b) from cord blood, c) from 5 days old newborns, and 6 month old infants were used for the experiments. For methodological reasons in the first part of our studies we have chosen: two sulfonamides - sulfamethazine and sulfamethoxasole, chlorpromazine and sodium salicylate. In the experiments two different techniques were used 1) equilibrium dialysis, 2) ultrafiltration. On the basis of the results obtained in animals as well as in human beings it was noted that the degree of drug binding to plasma proteins in newborns was different from that observed in adults, it may be higher or lower according to the drug used. The knowledge of this fact is of great importance, and should be taken into consideration in the calculation of proper dosage of various drugs in the newborns and infants.

Adult↗
PubMed1986

Ex vivo perfusion of plasma over protein A columns in human mammary adenocarcinoma. Role of the Fc-binding capacity of protein A in the side effects and the tumoricidal response.

Plasma of twelve patients presenting with a metastic mammary adenocarcinoma was perfused ex vivo over columns of protein A covalently linked to crystalline silica. The plasma of seven patients (group A) was perfused over columns of protein A exhibiting a normal Fc-binding capacity and the plasma of five (group B) over columns of protein A in which the Fc-binding capacity was destroyed. In group A, all patients experienced acute, easily manageable, side effects (hypotension, chills, mild fever, leucocytosis and pain in tumour sites) during or immediately after the immunoadsorption procedures, and three exhibited an objective partial regression after two to five sessions. In contrast, none of the patients from group B developed any acute side effects and all showed evident progression of their disease during the treatment. Tumour cells in all stages of destruction, sometimes surrounded by extensive fibrosis, were seen in biopsies of patients A. However, focal areas of active tumour proliferation were always present in these patients. These data confirm that ex vivo perfusion over protein A columns of plasma from patients with cancer can induce a tumoricidal response in some instances and show that the Fc-binding capacity of protein A is most probably responsible for the necrolytic response and the side effects.

Adenocarcinoma↗
PubMed1997

Effects of carbamazepine treatment on pain threshold values and brain serotonin levels in rats.

The administration of carbamazepine to rats caused a significant increase in pain threshold values. Furthermore, treatment with carbamazepine lowered the concentration of tryptophan bound to plasma proteins and elevated the brain serotonin values. The high brain serotonin levels, observed in carbamazepine-treated rats, are probably attributable to an increased availability of brain tryptophan, since this amino acid has been substantially removed from the plasma protein compartment by carbamazepine treatment, which exhibits a high binding capacity to plasma proteins. The analgesic effects caused by carbamazepine administration have been attributed to increased levels of brain serotonin which is involved in the control of pain transmission.

Administration, Oral↗
PubMed2006

Saturable binding of indisulam to plasma proteins and distribution to human erythrocytes.

The anticancer agent indisulam has a nonlinear pharmacokinetic profile, which may be partly related to saturable binding to blood constituents. To gain insight into the complex nonlinear behavior of indisulam, we investigated binding to plasma proteins and erythrocytes. The purpose of the study was to develop a physiological model for the distribution of indisulam in blood. Concentrations of radiolabeled indisulam were measured in vitro 1) in total plasma and in ultrafiltrate to investigate plasma protein binding, 2) in erythrocytes and in plasma to investigate distribution to erythrocytes, and 3) in erythrocyte membranes to investigate nonspecific binding in erythrocytes. For in vivo assessment, 21 patients received 400 to 900 mg/m2 indisulam in a 1- or 2-h infusion. Total and free concentrations in plasma and concentrations in erythrocytes were determined at multiple time points. In vitro plasma protein binding was described by a Langmuir model with a maximal binding capacity (Bmax = 767 microM) and an equilibrium dissociation constant (KD = 1.02 microM). The maximal capacity of plasma protein binding in vivo corresponded to albumin levels. The bound concentration in erythrocytes was described by a two-site model, comprising a saturable and a nonspecific binding component. The saturable component (Bmax = 174 microM) may correspond to binding to carbonic anhydrase. The physiological model adequately described the nonlinear disposition of indisulam in whole blood. Indisulam was bound to plasma proteins and distributed to erythrocytes in a saturable manner. These saturable processes may be attributed to binding to albumin (in plasma) and to carbonic anhydrase (in erythrocytes).

Antineoplastic Agents↗
PubMed1980

[Binding capacity of the testosterone-binding plasma protein in 2 wild mammals with cyclic testicular activity, the fox and badger].

The binding capacity of the plasma testosterone binding globulin (TeBG) as determined by the equilibrium dialysis method, in fox and badger, was shown to wary in relation to the seasonal endocrine activity of the testis. During the winter breeding period, the TeBG binding capacity was low in the fox and high in the badger, whereas an opposite situation prevailed during the sexual quiescence phase. Independent of those seasonal variations, the binding capacity of TeBG was always lower in fox than in badger.

Animals↗
PubMed1987

Measurement of free cortisol and the capacity and association constant of cortisol-binding proteins in plasma of foals and adult horses.

A direct method for measuring the capacity of the high-affinity binding protein, CBG, based on charcoal adsorption, was validated for use in the horse. Several unique aspects of cortisol binding in the horse were observed: (1) CBG content at birth was the lowest of any species studied, (2) CBG concentration increased with age whereas in other species it decreases, (3) the plasma of the new born foal has a binding protein, not reported for other species, which binds as much cortisol as does CBG. Its capacity and affinity are intermediate between albumin and CBG. It may be involved prenatally in increasing dam to fetus transfer of cortisol, and post-natally in buffering the effects of the huge stress-related peripartum release of cortisol.

Aging↗
PubMedDate not supplied

Plasma endotoxin concentration and endotoxin binding capacity of plasma acute phase proteins in cirrhotics with variceal bleeding: an analysis by new methods.

Plasma endotoxin levels in 12 cirrhotics with bleeding from oesophageal varices and 50 cirrhotics without bleeding were measured by the chromogenic assay after the pretreatment of sample by perchloric acid (HClO4) and triethylamine. Endotoxin in cirrhotics with bleeding from varices was significantly higher than those without bleeding. In patients with bleeding, endotoxin increased for 3 days after the bleeding, first in the supernatant fraction and then in the precipitate fraction by HClO4 treatment. Peak plasma alpha 1-acid glycoprotein and haptoglobin were observed 3 days after the bleeding. Alpha 1-antitrypsin gradually increased for 14 days. Transferrin did not markedly change. The endotoxin-binding capacity of transferrin and alpha 1-acid glycoprotein increased immediately after bleeding and thereafter decreased, but that of alpha 1-antitrypsin tended to increase in the recovery period. In summary, the plasma endotoxin concentration and endotoxin-binding capacity of alpha 1-acid glycoprotein and transferrin were shown to have increased after bleeding from varices by this new method. There may be a close relationship between endotoxaemia and acute phase reaction in this situation.

Acute-Phase Proteins↗
PubMed1985

Annual and diurnal patterns of plasma calcium fractions in anuran Rana pipiens.

Ionized calcium [Ca2+] in the amphibian Rana pipiens was measured over 18 mo. An annual variation about the mean of 1.10 mmol/l was observed that peaked in April (1.36 mmol/l) and attained minimal levels in October (0.84 mmol/l). Plasma total calcium [Ca]t, plasma proteins, and the bound calcium fraction also exhibited annual oscillations. The annual mean binding capacity of plasma proteins for calcium was established at 0.0175 mmol/g. Of the plasma total calcium in spring animals, nonprotein-bound calcium complexes [Ca]c were less than 3% of the total whereas 80% was composed of [Ca2+] and 17% as protein-bound calcium [Ca]pb. In autumn [Ca2+] composed 40%, [Ca]pb 30%, and [Ca]c 30% of plasma total calcium. An equilibrium exists between [Ca2+] and [Ca]c, which maintains a combined annual mean of 1.48 mmol/l calcium. Diurnal variations superimposed on the annual cycles are modulated by apparent movement of plasma water and an intrinsic 12-h rhythm for [Ca2+]. No definite associations could be made with the entrainment of specific rhythms of the three calcium fractions with the light-dark cycle.

Animals↗
PubMed1980

[Study of the binding between uric acid and plasma proteins (author's transl)].

The Authors have analyzed the complex problems of the possible binding between uric acid and plasma proteins using two methods consisting of serum ultrafiltration at 22 degrees C or electrophoresis on different supports with successive specific coloration of the free and bound uric acid. The percentage of free and bound uric acid was established in serum from normal subjects, patients with primary gout, patients with renal insufficiency treated by dialysis and subjects with type IV dyslipidemia. The Authors discuss the results obtained as regards the possible role played by urate-plasma proteins binding in the interpretation of a genetic defect present in gouty patients involving a diminished uric acid binding capacity of plasma proteins.

Blood Proteins↗
PubMed1975

Discrepancy between the measurement of thyroxine-binding prealbumin plasma level and binding capacity in protein-calorie malnutrition.

The measurement of thyroxine-bindung prealbumin (TBPA) in protein-calorie malnutrition by two different techniques leads to the recognition of an unexpected discrepancy. Whereas TBPA plasma levels as measured by immunodiffusion are markedly decreased to 29.3% of the normal, those recorded by maximal binding capacity (TBPAcap) are characterized by a wide dispersion. In the control group, the ratio between TBPAcap and TBPA plasma level is 9.1. In the malnourished group on admission, the same ratio is 30.0. The possibility of a qualitative effect in the tetrameric TBPA structure, with the binding of additional thyroxine (T4) molecules on the secondary binding sites, has been investigated. This hypothesis has been discarded by Scatchard plot studies. The normal 1:1 molar ratio between TBPA and T4 is unaffected in protein-deficient patients. Discrepant results obtained for TBPAcap and TBPA levels appear to be the consequence of low plasma protein levels, leading to an artifact in the electrophoretic method.

Blood Protein Electrophoresis↗
PubMed1987

Protein-bound polyamines in the plasma of mice grafted with the Lewis lung carcinoma.

Protein-bound polyamines were isolated from the plasma of mice using antipolyamine antibodies covalently linked to magnetic latex spheres. Their subsequent separation by polyacrylamide gel electrophoresis (PAGE) showed that in plasma from normal mice, 3 proteins (27, 55 and 82 kDa) carrying polyamines could be visualized, whereas in mice bearing the Lewis lung carcinoma at least 8 other proteins of higher molecular mass (5 of 94, 110, 130, 145 and 160 kDa, and 3 of greater than 170 kDa) had bound polyamines. These protein-bound polyamines could be detected from the first week after tumour graft; they increased during the second and third week but decreased thereafter. These proteins were not bound by immunolatex spheres preincubated with spermine bound to a protein-carrier insulin. Moreover, the appearance of these protein-bound polyamines was not a consequence of the inflammatory process since in mice infected with heat-inactivated Brucella abortus, with the exception of a 65 kDa protein, polyamines were bound to the same proteins found in normal mice. In mice grafted with the Lewis lung carcinoma the concomitant decrease in transglutaminase-mediated polyamine (e.g. putrescine) binding capacity of plasma proteins provides additional evidence for the presence in vivo of polyamines already bound to plasma proteins.

Animals↗