BINDING OF 5α-ANDROSTANE-3α,17β-DIOL TO HUMAN PLASMA PROTEINS

1973 ◽  
Vol 57 (2) ◽  
pp. 289-298 ◽  
Author(s):  
A. F. CLARK ◽  
C. E. BIRD
Keyword(s):  
Human Plasma ◽  
Plasma Proteins ◽  
Association Constant ◽  
Equilibrium Dialysis ◽  
Paper Electrophoresis ◽  
Mean Value ◽  
Albumin Fraction ◽  
The Mean ◽  
Apparent Association ◽  
Apparent Association Constant

SUMMARY The binding of 5α-androstane-3α,17β-diol to human plasma proteins was studied by equilibrium dialysis. The mean value of 96·6% for men was significantly less than that of 97·5% for women. These values are higher than those found for 5α-dihydrotestosterone (95·0 and 97·3%, respectively) and for testosterone (92·4 and 95·3%, respectively). When the distribution of labelled steroid in the different protein fractions was studied by paper electrophoresis, male plasma showed a larger fraction of 5α-androstane-3α,17β-diol radioactivity in the albumin fraction and less in the β-globulin area than did female plasma. Similar finding were made when 5α-dihydrotestosterone was studied. No inter-α-globulin peak of radioactivity was found for 5α-androstane-3α,17β-diol and 5α-dihydrotestosterone as occurs for testosterone. Albumin binds more 5α-androstane-3α,17β-diol than 5α-dihydrotestosterone or testosterone when studied by equilibrium dialysis and this is due to a higher apparent association constant between albumin and the dihydroxysteroid.

THE BINDING OF CORTISOL BY OVINE PLASMA PROTEINS

1967 ◽  
Vol 37 (3) ◽  
pp. 261-268 ◽  
Author(s):  
J. Y. F. PATERSON ◽  
F. HILLS
Keyword(s):  
Human Plasma ◽  
Plasma Proteins ◽  
Binding Capacity ◽  
Equilibrium Dialysis ◽  
Affinity Constant ◽  
Albumin Solution ◽  
Plasma Albumin ◽  
The Mean ◽  
Mean Concentration

SUMMARY Albumin was isolated from ovine plasma and its affinity for cortisol was determined by equilibrium dialysis at 37°. The value of Ka[σpa] for a 1 % (w/v) albumin solution was 0·275 which is similar to the value for human plasma albumin. The affinity constant of transcortin in ovine plasma was determined by equilibrium dialysis of diluted plasma at several concentrations of cortisol. The value found, Kt (37°) = 0·87 x 108 l./mole, is close to that found for human plasma transcortin by Mills (1962). The concentration of transcortin in ovine plasma, expressed as cortisolbinding capacity, was 6–49 μg. (mean 24 μg.) cortisol/l. These concentrations are much lower than those found in human plasma. The observation of Lindner (1964) that cortisol binding capacity did not increase during pregnancy in sheep has been confirmed. In sheep which were accustomed to handling, the mean concentration of cortisol in plasma was 17·8 μg./l. and of this amount 59% was bound to transcortin, 19 % to albumin and 22 % was not bound to protein.

PROTEIN BINDING OF PLASMA CORTISOL IN THE FOETAL LAMB NEAR TERM

1975 ◽  
Vol 67 (3) ◽  
pp. 333-341 ◽  
Author(s):  
R. J. FAIRCLOUGH ◽  
G. C. LIGGINS
Keyword(s):  
Plasma Proteins ◽  
Binding Capacity ◽  
Equilibrium Dialysis ◽  
Progressive Increase ◽  
Mean Value ◽  
Affinity Constant ◽  
Total Cortisol ◽  
The Mean ◽  
Near Term ◽  
Foetal Lamb

SUMMARY Binding of cortisol to plasma proteins was studied in the foetal lamb by equilibrium dialysis at 37 °C. At 122 days of pregnancy the mean level of transcortin expressed as cortisolbinding capacity was 28 ± 6 (s.d.) ng cortisol/ml plasma. During the last 14 days of pregnancy there was a progressive increase in transcortin-binding capacity to 85 ± 14 ng cortisol/ ml plasma. A sharp increase in the concentration of both protein-bound and unbound cortisol was observed over the same period. A rise in the concentration of total cortisol from around 3 to 42 ng/ml was associated with an increase in unbound cortisol from 0·2 to a maximum of 2·1 ng/ml. The concentration of albumin-bound cortisol was approximately equal to that of unbound cortisol. The mean value for the transcortin–cortisol affinity constant was 1·15 × 108 l/mol. It is concluded that an increase in transcortin-binding capacity is partly responsible for the prepartum increase of corticosteroid levels observed in normal foetal lambs.

A pharmacokinetic study of Genetaxyl (G) together with cyclosporin A (CsA) administered orally in cancer patients

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 12002-12002
Author(s):  
C. Liau ◽  
E. Lepper ◽  
H. Wang ◽  
M. Yang ◽  
T. Chiou ◽  
...  
Keyword(s):  
Equilibrium Dialysis ◽  
Volume Of Distribution ◽  
Mean Value ◽  
Phase Ii Trials ◽  
Patients With Cancer ◽  
The Mean ◽  
High Concentrations ◽  
Apparent Bioavailability ◽  
Dose Levels ◽  
Dose Dependent

12002 Background: Oral administration of paclitaxel given with CsA has shown promising activity in Phase II trials, but the apparent bioavailability is low and dose-dependent due to the presence of high concentrations of Cremophor EL (CrEL). We hypothesized that the use of a novel oral paclitaxel formulation containing only 20% CrEL (Genetaxyl [G]; Genovate Biotechnology Ltd., Taiwan), given with CsA is associated with an improved pharmacokinetic (PK) profile. Methods: Cohorts of 6 patients with cancer were treated with oral G at a dose of 60, 120, or 180 mg/m2 and 10 mg/kg of oral CsA in cycle 1. In cycle 2, patients received IV G (175 mg/m2, 3-h infusion). Three additional patients received generic IV paclitaxel (GIP). Serial blood samples were analyzed by LC/MS/MS and equilibrium dialysis, to determine total and unbound paclitaxel PK. Results: The mean (± SD) total paclitaxel AUCs were 1299±189, 1682±636, and 2204±1407 ng.h/mL at the 3 consecutive dose levels, suggesting nonlinear PK. However, based on unbound AUC, the oral bioavailability was dose-independent (P=.62), with a mean value of 37.2±18.6% (n=15). As expected, the total paclitaxel AUC following IV G (9024±4648 ng·h/mL) was lower than that for IV GIP (13,732±3983 ng·h/mL), as a result of increased clearance (39.6 vs 18.3 L/h) and a larger volume of distribution (768 vs 268 L). Interestingly, the unbound paclitaxel AUC was similar between the two IV formulations (P=.25), as the ratio of unbound/total paclitaxel for G was 2.5 times higher than that for GIP (12.5 vs 4.9%). Toxicity profiles were mild, with only 2 patients experiencing ≥ Gr 3 myelosuppression following oral G at 180 mg/m2. Conclusions: The mean bioavailability of paclitaxel following oral Genetaxyl with CsA was about 37%, which is higher than that observed previously with paclitaxel (range, 21–31%). Further clinical exploration of oral Genetaxyl in taxane-sensitive diseases is warranted. [Table: see text]

scholarly journals Some Physiological Factors Affecting the Binding of Cortisol by Human Plasma Proteins

1977 ◽  
Vol 14 (1-6) ◽  
pp. 35-38 ◽  
Author(s):  
J. D. Few ◽  
J. R. Haspineall
Keyword(s):  
Steady State ◽  
Human Plasma ◽  
Plasma Proteins ◽  
Gel Filtration ◽  
Physiological Factors ◽  
Mean Values ◽  
Factors Affecting ◽  
Free Cortisol ◽  
The Mean

Steady-state gel filtration has been used to study the binding of cortisol to human plasma proteins in vitro. Raising the temperature from 37°C to 41°C results in the mean proportion of free (non-protein-bound) cortisol rising approximately from 7% to 11%. Addition of cortisol to plasma ≡ 275 nmol/l) also increased the proportion of free cortisol by approximately 50%. Cortisone is less strongly bound to plasma proteins than cortisol. The mean values (±S.D.) for five samples were free cortisol 8.4 ± 1.1% and free cortisone 26.0±3.8%.

scholarly journals Synthesis and surface grafting of a β-cyclodextrin dimer facilitating cooperative inclusion of 2,6-ANS

2015 ◽  
Vol 11 ◽  
pp. 514-523 ◽  
Author(s):  
Lars W Städe ◽  
Thorbjørn T Nielsen ◽  
Laurent Duroux ◽  
Reinhard Wimmer ◽  
Kyoko Shimizu ◽  
...  
Keyword(s):  
Fluorescence Spectroscopy ◽  
Sulfonic Acid ◽  
Total Internal Reflection ◽  
Association Constant ◽  
Guest Molecule ◽  
Solid Surfaces ◽  
Surface Grafting ◽  
Cyclodextrin Dimer ◽  
Apparent Association ◽  
Apparent Association Constant

A novel β-cyclodextrin (β-CD) dimer was synthesized and surface-grafted by click chemistry onto azide-functionalized quartz surfaces in order to introduce the cooperative features of the β-CD dimer to solid surfaces. Using NMR and fluorescence spectroscopy, it is shown that the free β-CD dimer forms a 1:1 complex with the fluorescent guest molecule, 2-anilinonaphthalene-6-sulfonic acid (otherwise known not to form 1:2 complexes with parent β-CD), with an apparent association constant of 7300 M−1. Further, it is shown using total internal reflection fluorescence spectroscopy that the inclusion of the fluorescent guest into both cavities of the β-CD dimer is maintained when grafted onto a solid surface.

THE EFFECT OF GLUCOSE AND FRUCTOSE INGESTION ON THE ADRENALINE AND NORADRENALINE LEVELS IN HUMAN PLASMA

1954 ◽  
Vol 11 (3) ◽  
pp. 298-303 ◽  
Author(s):  
H. WEIL-MALHERBE ◽  
A. D. BONE
Keyword(s):  
Human Plasma ◽  
Blood Sugar ◽  
Blood Sugar Level ◽  
Mean Value ◽  
Initial Value ◽  
Subsequent Recovery ◽  
The Mean ◽  
Effect Of Glucose ◽  
Venous Plasma ◽  
Noradrenaline Levels

SUMMARY 1. The ingestion of 50 g glucose by fasting subjects led to an increase of the concentration of adrenaline in venous plasma amounting to a mean value of 55% after 10 min. The effect was almost as marked 5 min after the glucose meal when the mean blood sugar level had only gone up by 3%. During the period 10–60 min after the glucose meal the concentration of adrenaline in the plasma gradually returned to its initial value. 2. The concentration of noradrenaline in the plasma was not significantly changed after a glucose meal. 3. The ingestion of 50 g fructose by fasting subjects was without effect on the concentration of adrenaline or noradrenaline in the plasma. 4. A glucose meal given 15 min before an intravenous injection of insulin slightly modified the effect of insulin on the concentration of adrenaline by delaying its initial fall and also its subsequent recovery. It is suggested that the rise in the level of adrenaline after a glucose meal is caused by a decrease in the hepatic utilization of the hormone.

A fluorogenic substrate for angiotensin-converting enzyme in plasma.

1978 ◽  
Vol 24 (9) ◽  
pp. 1539-1542 ◽  
Author(s):  
F S Russo ◽  
A V Persson ◽  
I B Wilson
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Human Plasma ◽  
Mean Value ◽  
Converting Enzyme ◽  
Fluorogenic Substrate ◽  
Fluorescent Substrate ◽  
The Mean ◽  
Hydrolysis Of ◽  
Assay Conditions

Abstract A simple, sensitive, and reproducible assay for angiotensin-converting enzyme is described. It is based on the hydrolysis of the minimally fluorescent substrate p-nitrobenzyloxycarbonylglycyl-L-tryptophylglycine to the products p-nitrobenzyloxycarbonylglycine and the highly fluorescent L-tryptophylglycine. The L-tryptophylglycine was analyzed by fluorometry (lambda excitation = 285 nm; lambda emission = 350 nm). The mean value for human plasma (serum) is 16.5 nmol of substrate hydrolyzed per minute per milliter of plasma under the described assay conditions.

Radioimmunoassay of Calcitonin in Human Plasma

1974 ◽  
Vol 20 (3) ◽  
pp. 337-339 ◽  
Author(s):  
Omega L Silva ◽  
Richard H Snider ◽  
Kenneth L Becker
Keyword(s):  
Human Plasma ◽  
Mean Value ◽  
Total Calcium ◽  
Peripheral Plasma ◽  
Specific Radioimmunoassay ◽  
Ionic Calcium ◽  
Calcium Infusion ◽  
Normal Man ◽  
The Mean ◽  
Normal Men

Abstract A sensitive, specific radioimmunoassay of calcitonin is described, suitable for measuring the hormone in peripheral plasma of normal man. With this assay we have demonstrated that calcitonin is detectable under ba sal conditions and the concentrations respond to induced and spontaneous hypercalcemia and induced hypocalcemia. The mean value for basal calcitonin of normal men was 182 pg/ml (range 63-450); patients with hypercalcemia of various etiologies had a statistically significant higher mean value of 510 pg/ml (range 110-2700). In calcium-infusion studies, concentrations of both total calcium and ionic calcium correlated well with plasma calcitonin (0.77 and 0.84, respectively). These findings strongly suggest that calcitonin is of physiologic importance in man.

CORTISOL BINDING TO PLASMA PROTEINS IN MAN IN HEALTH, STRESS AND AT DEATH

1967 ◽  
Vol 39 (4) ◽  
pp. 571-591 ◽  
Author(s):  
D. MURRAY
Keyword(s):  
Protein Binding ◽  
Binding Sites ◽  
Plasma Proteins ◽  
Normal Subjects ◽  
Biologically Active ◽  
The Mean ◽  
Mean Concentration ◽  
Apparent Association ◽  
Venous Plasma

SUMMARY A method is described for determining the degree of binding by plasma proteins of cortisol by a technique of pressure ultrafiltration at 37° after addition of radioactively labelled cortisol. In normal subjects, the mean concentration of transcortin binding sites was 5·82 × 10−7 moles/l. and the apparent association constant at 37° was 4·27 × 107 l./mole. Evidence of increased protein binding of cortisol was obtained in oestrogen-treated subjects and in women in the last 3 months of pregnancy. In the latter subjects normal levels of non-protein bound cortisol were found. The mean level of non-protein bound cortisol in eight men treated with stilboestrol was increased, but normal levels were present in four of these subjects. The protein binding of cortisol in three patients with Cushing's syndrome and in three patients with Addison's disease was normal. Thirty-five% of cortisol in adrenal venous plasma was in the unbound state. Increased levels of plasma 17-hydroxycorticosteroids (17-OHCS) were found in patients in stressful situations (post-operative states, infections and burns). There was no evidence of increased protein binding of cortisol. Patients at death had increased levels of plasma 17-OHCS including three patients who had been on long-term steroid therapy. There was no evidence of increased protein binding of cortisol. On the contrary, there was some evidence of a decrease in transcortin binding sites. It is concluded that stressful situations in man, regardless of the outcome, are associated with increased plasma levels of biologically active cortisol.

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