Changes in serum somatomedin A and its binding to kidney membranes in growing rats

1981 ◽  
Vol 97 (3) ◽  
pp. 352-357 ◽  
Author(s):  
Naomi Hizuka ◽  
Kazue Takano ◽  
Kazuo Shizume ◽  
Yoko Hasumi
Keyword(s):  
Binding Capacity ◽  
Inverse Correlation ◽  
Close Correlation ◽  
Serum Levels ◽  
Affinity Constant ◽  
Scatchard Analysis ◽  
Receptor Sensitivity ◽  
Growing Rats ◽  
The Mean ◽  
Clear Change

Abstract. Changes in serum somatomedin A levels and [125I]somatomedin A binding to membrane fractions from kidney were studied in rats 1–80 days of age. The mean level of serum somatomedin A was 0.80 U/ml at birth and increased with age; at 80 days the mean level was 7.41 ± 0.67 U/ml. There was a close correlation between serum levels of somatomedin A and body weight. Labelled somatomedin A binding to membrane fractions from kidney was highest at birth and decreased with age up to 50 days. In Scatchard analysis of the data the affinity constant did not show a clear change with age, but the binding capacity decreased with age up to 30 days. An inverse correlation was observed between serum somatomedin A levels and labelled somatomedin A binding to membrane fractions from kidney. Compared to changes in circulating somatomedin A, the change in tissue binding was modest. This observation suggests that other circulating growth factors not measured by this radioreceptor assay or altered post-receptor sensitivity to somatomedins may be involved in growth.

TRIIODOTHYRONINE BINDING TO LYMPHOCYTES FROM EUTHYROID SUBJECTS AND A PATIENT WITH PERIPHERAL RESISTANCE TO THYROID HORMONE

1976 ◽  
Vol 83 (1) ◽  
pp. 64-70 ◽  
Author(s):  
Kristian Liewendahl
Keyword(s):  
Thyroid Hormone ◽  
Binding Sites ◽  
Binding Capacity ◽  
Human Lymphocytes ◽  
Peripheral Resistance ◽  
Subsequent Treatment ◽  
Affinity Constant ◽  
Prolonged Incubation ◽  
Resistance To Thyroid Hormone ◽  
The Mean

ABSTRACT Triiodothyronine (T3) binding to Ficoll-Isopaque purified human lymphocytes was studied. During incubation of lymphocytes with [125I]T3 in a calcium-free medium at 37°C, maximal uptake of T3 in nuclei occurred after 2 h and declined after prolonged incubation. Incubation of lymphocytes with T3 concentrations ranging from 1 × 10−11 to 1 × 10−9 mol/l and subsequent treatment with Triton X-100 to strip off [125I]T3 bound with low affinity was used for the estimation of affinity and capacity of nuclear T3 binding sites. The mean equilibrium affinity constant (Ka) estimated with the Scatchard method in 11 euthyroid healthy subjects was 4.5 × 109 1/mol, and the mean maximal binding capacity 25 × 10−15 mol/100 μg DNA. In a female patient with peripheral resistance to thyroid hormone action, the estimated Ka was 3.5 × 109 1/mol and the number of T3 binding sites 37 × 10−15 mol/100 μg DNA. Although not statistically different from the mean value in euthyroid subjects, this Ka value was outside the range of control values observed and was considered presumptive evidence that the nuclear T3 receptors in this patient have abnormally low affinity for its ligand. The nuclear T3 binding capacity in this patient was significantly increased.

BONE PHOSPHORUS METABOLISM IN VITRO IN THYROTOXICOSIS

1960 ◽  
Vol XXXIII (IV) ◽  
pp. 577-583 ◽  
Author(s):  
C. A. Hernberg
Keyword(s):  
Bone Formation ◽  
Binding Capacity ◽  
Phosphorus Uptake ◽  
Close Correlation ◽  
Phosphorus Metabolism ◽  
Relative Percentage ◽  
Bone Powder ◽  
The Mean ◽  
Normal Controls

ABSTRACT The capacity of bone to take up phosphorus from an incubation medium was used as an indicator of bone formation in 31 cases of thyrotoxicosis. Eleven patients with no thyrotoxicosis served as controls. Three cases of hypothyroidism and one of hyperparathyroidism were also studied. As compared with the phosphorus binding capacity of a standard bone powder the relative percentage of phosphorus uptake in the normal controls was 101.6 ±4.9. The values tended to decrease with increasing age. In the cases of hypothyroidism the mean relative percentage was 97. In the hyperparathyroid case it was 140. The cases of thyrotoxicosis showed values between 99 and 137, with a mean of 118, st. dev. 12.1. There was no close correlation with the severity of thyrotoxicosis or with the nature of the goitre.

scholarly journals A new unextracted-sample radioimmunoassay method for hepatic endogenous nuclear l-tri-iodothyronine content. Validity of its use in determining nuclear receptor binding characteristics

1982 ◽  
Vol 208 (3) ◽  
pp. 641-649 ◽  
Author(s):  
Toshihiro Yagura ◽  
Paul G. Walfish
Keyword(s):  
Receptor Binding ◽  
Binding Capacity ◽  
Nuclear Extract ◽  
Affinity Constant ◽  
Lower Sensitivity ◽  
Scatchard Analysis ◽  
Binding Characteristics ◽  
Radioimmunoassay Method ◽  
True Values ◽  
Good Agreement

Endogenous l-tri-iodothyronine content in an hepatic nuclear extract was measured by a new unextracted-sample radioimmunoassay method using 8-anilinonaphthalene-1-sulphonic acid to inhibit the l-[125I]tri-iodothyronine binding to the nuclear l-tri-iodothyronine receptor within the extract. For this method, the lower sensitivity limit was 3.125 pg/tube, the recovery of added l-tri-iodothyronine was 90–120%, and the between-assay coefficient of variation was 10%. The amount of endogenous l-tri-iodothyronine was 10–40 pg/0.2 ml of hepatic nuclear extract from euthyroid rats, compared with less than 3.125 pg/0.2 ml from thyroidectomized rats. The results obtained by this new method were compared with a Sephadex G-25 column extracted-sample radioimmunoassay method and showed a good agreement. The values for the endogenous l-tri-iodothyronine content were utilized to correct for the l-tri-iodothyronine concentration within the binding assay mixture in order to accurately determine by Scatchard analysis the binding characteristics of the nuclear l-tri-iodothyronine receptor. The validity of the correction for endogeneous l-tri-iodothyronine was demonstrated by using a nuclear extract from a thyroidectomized rat which was preincubated with a small known amount of l-tri-iodothyronine before determining the nuclear l-tri-iodothyronine receptor binding characteristics. When the Scatchard plots were corrected for the preincubated dose, the results obtained were similar to true values, but they were falsely lower when not corrected. It is concluded that the necessity and validity of using endogenous l-tri-iodothyronine corrections in the Scatchard analytical computations of the nuclear l-tri-iodothyronine receptor binding characteristics has been demonstrated, being particularly more important for affinity constant than maximum binding capacity.

scholarly journals The identification of ketotifen as a novel cardioprotective agent in patients undergoing anthracyclines chemotherapy

2021 ◽  
Author(s):  
hosny elewa ◽  
Naser elberay ◽  
Walaa Keshk ◽  
Hamada Abulkhair
Keyword(s):  
Breast Cancer ◽  
Binding Capacity ◽  
Serum Levels ◽  
Total Iron ◽  
Control Group ◽  
Controlled Clinical Trial ◽  
Iron Binding ◽  
Total Iron Binding Capacity ◽  
The Mean ◽  
Iron Binding Capacity

Objective: The present study aimed to investigate the possible cardioprotective effects of ketotifen and to assess its activity as an iron-chelating agent in patients receiving anthracyclines for the treatment of breast cancer. Patients & Methods: This was a randomized, prospective, controlled clinical trial. One hundred eleven eligible patients with breast cancer (age range, 30-60 years) were scheduled to receive anthracyclines chemotherapy. The patients were divided into two groups: Patients (n = 56) assigned to the ketotifen group received ketotifen 1 mg three times daily for six consecutive cycles of treatment, and patients assigned to the control group (n = 55) without ketotifen treatment. The echocardiogram for each patient was recorded two times at baseline and the end of the study. As well, blood samples were collected from all patients. Results: The findings showed a statistically significant reduction in the mean serum levels of common cardiotoxicity accompanied biomarkers in the ketotifen group compared with the control group (P ≤ 0.05). The mean serum levels of total iron-binding capacity were significantly elevated in the ketotifen group (P ≤ 0.001). There was a direct correlation between the mean serum levels of iron and that of lactate dehydrogenase (LDH) (r = + 0.79). On the other hand, there were indirect correlations between mean serum levels of LDH and both the percentage of ejection fraction and the total iron-binding capacity (r = - 0.69 and -0.697, respectively). Conclusion: Oral administration of ketotifen appears to be efficient and safe as a novel cardioprotective agent for the prevention of anthracyclines induced cardiotoxicity. Additionally, ketotifen suggested a beneficial effect in iron overload inducing diseases such as COVID-19.

scholarly journals Novel use of Ketotifen as a cardio-protective agent in patients undergoing anthracycline chemotherapy

2021 ◽  
Author(s):  
hosny elewa ◽  
Naser elberay ◽  
amany elsharif ◽  
Walaa Keshk ◽  
zeinab zalat
Keyword(s):  
Breast Cancer ◽  
Binding Capacity ◽  
Serum Levels ◽  
Total Iron ◽  
Control Group ◽  
Iron Binding ◽  
Total Iron Binding Capacity ◽  
The Mean ◽  
Iron Binding Capacity ◽  
Anthracycline Chemotherapy

Objective: The present study aimed to investigate the possible cardioprotective effects of ketotifen and to assess its activity as an iron-chelating agent in patients receiving anthracyclines for the treatment of breast cancer. Patients & Methods: This was a randomized, prospective, controlled clinical trial. 111 eligible patients with breast cancer (age range, 30-60 year) were scheduled to receive anthracycline chemotherapy. The patients divided into two groups: Patients (n=56) assigned to The ketotifen group received ketotifen 1 mg three times daily for six consecutive cycles of treatment, and patients assigned to The control group (n= 55) without ketotifen treatment. The echocardiogram for each patient was recorded two times at baseline and at the end of the study. As well, blood samples were collected from all patients. Results: The findings showed a statistically significant reduction in the mean serum levels of common cardiotoxicity accompanied biomarkers in The ketotifen group compared with The control group (P ≤ 0.05). The mean serum levels of total iron-binding capacity was significantly elevated in The ketotifen group (P ≤ 0.001). There was a direct correlation between the mean serum levels of iron and that of lactate dehydrogenase (LDH) (r = + 0.79). On the other hand, there were indirect correlations between mean serum levels of LDH and both the percentage of ejection fraction and the total iron-binding capacity (r = - 0.69 and -0.697, respectively). Conclusion: Oral administration of ketotifen appears to be efficient and safe as a novel cardioprotective agent for the prevention of anthracyclines induced cardiotoxicity. Additionally, ketotifen suggested a beneficial effect in iron overload inducing diseases such as COVID-19.

Thionamides and arsenite inhibit specific T3 binding to the hepatic nuclear receptor

1990 ◽  
Vol 68 (3) ◽  
pp. 616-621 ◽  
Author(s):  
Shinko Takagi ◽  
Brian C. W. Hummel ◽  
Paul G. Walfish
Keyword(s):  
Nuclear Receptors ◽  
Nuclear Receptor ◽  
Specific Activity ◽  
Binding Capacity ◽  
High Specific Activity ◽  
Relative Mass ◽  
Affinity Constant ◽  
Scatchard Analysis ◽  
Therapeutic Effects ◽  
Inhibitory Effects

Methimazole (MMI) and propylthiouracil (PTU) are widely used for the treatment of Graves' disease. However, no studies have been reported on the action of these drugs on binding of L-triiodothyronine (T3) to the nuclear receptor. T3 receptors of rat liver nuclei, prepared by differential centrifugation, were extracted with 0.4 M KCl and 5 mM dithiothreitol (DTT). In the assessment of T3 binding to the DTT-reduced receptor, the hepatic nuclear extract was chromatographed on Superose 6 to remove DTT and isolate proteins of relative mass ≈ 50 000 (chromatographed nuclear receptors (CNRs)), prior to the addition of [125I]T3 of high specific activity (3300 μCi/μg; 1 Ci = 37 GBq). MMI or PTU at 2 mM reduced specific T3 binding to CNR by 84% and 85%, respectively. The inhibitory effects of these reagents and 2 mM sodium arsenite (which complexes dithiols) were additive. Scatchard analyses indicated that neither MMI nor PTU (at 2 mM) significantly altered the affinity constant (Ka) (from 2.41 × 109 to 1.74 × 109 M−1 for PTU and 1.79 × 109 M−1 for MMI), while they both decreased (p < 0.02) maximal binding capacity (from 0.36 ± 0.02 to 0.19 ± 0.02 pmol/mg protein for MMI and 0.17 ± 0.02 pmol/mg protein for PTU). Dose-response curves showed that 50% inhibition was attained at 0.6 mM PTU or 1.0 mM MMI with ≈25% inhibition by both at 0.1 mM. Artefactual binding effects by MMI and PTU on [125I]T3 were excluded by chromatography experiments. Similar results were obtained using nuclear receptors prepared from livers of hyperthyroid rats. Pretreatment of CNR for 1 h with 5 mM methyl methanethiosulfonate (an oxidant of thiol groups) abolished the inhibitory effects of PTU, MMI, or arsenite, but was not inhibitory in itself. From these studies it is concluded that (i) MMI and PTU could exert at least part of their therapeutic effects by inhibiting specific binding of L-T3 to its hepatic nuclear receptor; (ii) these inhibitory effects of MMI and PTU are likely due to an interaction with cysteine residues (some of which are not in a dithiol configuration) that are essential for T3 binding to its receptor; and (iii) binding of T3 is not inhibited by oxidation of receptor thiols to methyl dithiol groups.Key words: nuclear triiodothyronine (T3) receptor, methimazole, propylthiouracil, Scatchard analysis.

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.

scholarly journals Evaluation of serum levels of iron, total iron binding capacity, transferrin saturation and ferritin in chronic kidney disease patients vs. control group

2020 ◽  
Vol 2 (2) ◽  
Author(s):  
Hafsatu Maiwada Suleiman ◽  
Mohammed Amina ◽  
Ibrahim Abubakar ◽  
Yusuf Rasheed ◽  
Mohammed Jibril El-Bashir ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Serum Creatinine ◽  
Binding Capacity ◽  
Transferrin Saturation ◽  
Serum Levels ◽  
Control Group ◽  
Mean Values ◽  
The Mean ◽  
Iron Binding Capacity

The magnitude of chronic renal disease is enormous, as the prevalence of kidney failure is rising. Anaemia is a common complication of chronic kidney disease (CKD) that develops early in its course and becomes increasingly severe as the disease progresses. The aim is to evaluate the serum level of iron, Total Iron Binding Capacity (TIBC), transferrin saturation and ferritin in chronic kidney disease population in Zaria and control subjects. This study was conducted at ABUTH Zaria were 125 patients in various stages of CKD who presented at the nephrology clinic and equal number of apparently healthy age and sex matched controls were recruited. The mean (SD) age of patient and controls were 48 (14) years. These were made up of 53.6% males, and 46.4% females. Mean values of serum creatinine significantly higher in the patients (<0.0001). There was no significant difference in the mean values of iron (p=0.32) and TIBC (p=1.29) in both study groups. The patients had a significantly (p˂0.0001) higher mean value for ferritin and TSAT than the control group. There were higher serum creatinine and ferritin values in males than in females while higher serum TIBC, estimated creatinine clearance and iron were observed in females than males. Serum creatinine, ferritin and estimated creatinine clearance of male patients were found to be significantly higher with p-value of 0.002, 0.000 and 0.028 respectively than that of female patients. No significant differences were noted in serum levels of iron, TIBC and TSAT. Serum creatinine, ferritin and TSAT were found to be significantly elevated in CKD patients while serum Iron and TIBC were not.

Thioredoxin and glutaredoxin enhance the binding of L-triiodothyronine to its hepatic nuclear receptors

1989 ◽  
Vol 67 (8) ◽  
pp. 477-480 ◽  
Author(s):  
Shinko Takagi ◽  
Ganesh B. Bhat ◽  
Brian C. W. Hummel ◽  
Paul G. Walfish
Keyword(s):  
Glutathione Reductase ◽  
Nuclear Receptors ◽  
Nuclear Receptor ◽  
Binding Capacity ◽  
Specific Binding ◽  
Thioredoxin Reductase ◽  
Affinity Constant ◽  
Scatchard Analysis ◽  
Physiological Effects ◽  
Thioredoxin System

The influence of thioredoxin and glutaredoxin on binding of L-triiodothyronine (T3) to the rat hepatic nuclear T3 receptor was compared with that of the exogenous activator dithiothreitol. Specific [125I]T3 binding, the affinity constant, Ka, and the maximal binding capacity, MBC, were measured using whole nuclei, solubilized preparations of receptor, and chromatographed nuclear receptor. Both the thioredoxin system (thioredoxin, thioredoxin reductase, and NADPH) and the glutaredoxin system (glutaredoxin, glutathione reductase, glutathione, and NADPH) increased specific binding of T3 to nuclei, solubilized receptor, and chromatographed receptor significantly. Compared with the values obtained in the absence of added thiol (Ka = 1.6 ± 0.1 × 109 M−1 MBC = 1.7 ± 0.06 pM), the thioredoxin and glutaredoxin systems increased Ka by 147 and 112%, respectively, while decreasing MBC by 51 and 45%, respectively, when chromatographed receptor was used. The same tendency was observed with solubilized receptor. However, dithiothreitol increased Ka without affecting MBC when solubilized receptor was used. These results, the first demonstration of endogenous disulphide reductant systems enhancing binding of T3 to its receptor, suggest that the thioredoxin and (or) glutaredoxin systems may modulate the physiological effects of thyroid hormone.Key words: nuclear triiodothyronine (T3) receptor, thioredoxin, glutaredoxin, Scatchard analysis.

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.

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