A model-free approach to estimation of relative potency in dose-response curve analysis

1987 ◽  
Vol 252 (3) ◽  
pp. E357-E364 ◽  
Author(s):  
V. Guardabasso ◽  
D. Rodbard ◽  
P. J. Munson
Keyword(s):  
Dose Response ◽  
Goodness Of Fit ◽  
Nonlinear Least Squares ◽  
Relative Potency ◽  
Smoothing Spline ◽  
Enzyme Linked Immunosorbent Assay ◽  
Response Curves ◽  
Model Free ◽  
Dose Response Curves ◽  
Relative Potencies

We have developed a new, general approach to analysis of dose-response curves from bioassay, immunoassay (including radioimmunoassay, immunoradiouretic assay, enzyme-linked immunosorbent assay), and other experimental procedures. It provides a test for parallelism, similarity of shape, and a measure of relative potency for any set of two or more curves. The method uses a constrained smoothing spline function to estimate the curve shape, together with a nonlinear least-squares fitting technique to estimate parameters for relative potency and slope. The use of “constrained splines” permits the analysis of nonlinear dose-response curves that cannot be described by a simple model or equation such as the symmetric four-parameter logistic. A microcomputer program is used for the analysis, providing relative potencies and their SE and evaluation of goodness of fit

BIOLOGICALLY ACTIVE LUTEINIZING HORMONE (LH) IN PLASMA

1976 ◽  
Vol 83 (3) ◽  
pp. 454-465 ◽  
Author(s):  
P. Romaní ◽  
D. M. Robertson ◽  
E. Diczfalusy
Keyword(s):  
Menstrual Cycle ◽  
Dose Response ◽  
Gel Filtration ◽  
Biologically Active ◽  
Relative Potency ◽  
Response Curves ◽  
Plasma Pool ◽  
Dose Response Curves ◽  
Post Menopausal

ABSTRACT A recently described in vitro bioassay method for the measurement of biologically active LH (Van Damme et al. 1974) has been applied to the plasma of normally menstruating and post-menopausal women. The specificity of the procedure was established according to the following evidence: 1. Parallelism was observed between dose response curves obtained with serial dilutions of a standard LH preparation (HMG 2nd IRP) and plasma pools collected during the follicular phase, at the LH-peak, during the luteal phase and after menopause. 2. There was no evidence for the presence of any synergistic or antagonistic factor in the various plasma specimens. The assay design used to establish this consisted of assaying the standard and plasma pool separately and then together as a mixture followed by an asssessment of the difference (if any) in the potencies obtained. Strict additivity should yield a relative potency of 1.0. Plasma pools which were obtained every 2–3 days throughout the menstrual cycle were assayed using this design against the standard (HMG 2nd IRP) and against a mid-cycle plasma pool obtained at the time of the LH-peak. The latter was also assayed against partially purified plasma fractions obtained from a post-menopausal plasma pool after gel filtration and isoelectric focusing. With the exception of 3 assays, in which the estimates of relative potency were 0.91, 0.94 and 0.95, respectively, in 19 assays of additivity, the fiducial limits always included unity. 3. Non-detectable LH levels were found in the plasma or serum of either hypophysectomized or hypopituitary hypogonadal men or women treated with oestrogen/progestogen combined pills. 4. The presence of calf or human serum in the assay medium is an essential requirement for a valid comparison of standard and unknown preparations. In their absence, non-parallel dose response curves between plasma and standard were obtained. The other established criteria of reliability (sensitivity and precision) were also examined. The method is sufficiently sensitive (3.5–8.0 mIU/ml plasma; HMG (2nd IRP) as standard) for the measurement of LH throughout the cycle. The mean index of precision (λ) in 230 multiple assays was 0.040. It is concluded that the modified bioassay yields valid and reliable estimates of LH when applied to human plasma obtained throughout the menstrual cycle and after menopause.

Determination of the Therapeutic Mean Effective Doses of Several Anti-inflammatory Agents in Adjuvant Arthritic Rats

1974 ◽  
Vol 52 (4) ◽  
pp. 791-796 ◽  
Author(s):  
R. R. Martel ◽  
J. Klicius ◽  
F. Herr
Keyword(s):  
Dose Response ◽  
Probit Analysis ◽  
Relative Potency ◽  
Response Curves ◽  
Treatment Groups ◽  
Clinical Observations ◽  
Inflammatory Drugs ◽  
Dose Response Curves ◽  
Anti Inflammatory ◽  
Therapeutic Test

The large variation in the severity of the arthritic response of the adjuvant-injected rat often makes it impossible to obtain statistically manageable dose–response curves with anti-inflammatory drugs. Consequently, the relative potency of anti-inflammatory drugs generally was not established. In the present study, with a modification of the therapeutic test, reliable dose–response curves were obtained with seven anti-inflammatory drugs. With this method the "therapeutic" mean effective dose (ED50) and relative potency were calculated by probit analysis. Charles River rats were injected in the left hind paw with adjuvant. On day 14, rats with an injected paw volume of 4–6 ml that increased by at least 0.5 ml between days 10 and 14 were selected for drug treatment. Groups of 6–12 rats with a mean injected paw volume of 5–5.5 ml were formed. Dosing with compounds was started on day 14 and continued daily until day 22 (nine injections). Ninety-four percent of the arthritic control rats showed a further increase in injected paw size between days 14 and 22 (mean, 1.06 ± 0.12 ml) whereas rats dosed with anti-inflammatory compounds showed a dose-related decrease in paw size during the same period. A decrease of 0.5 ml or more between days 14 and 22 was considered to be a therapeutic effect, smaller decreases were taken as no effect. The oral ED50's in milligrams per kilogram were indomethacin, 0.22 ± 0.05; prednisolone, 3.49 ± 1.0; hydrocortisone, 12.4 ± 3.0; phenylbutazone, 13.27 ± 2.7; mefenamic acid 20.10 ± 5.8; aminopyrine, 129.95 ± 25.3; and aspirin, 279.0 ± 24.6. Except for aspirin, the relative potency of the compounds studied by this therapeutic test (chronic) was comparable to that reported for the acute carrageenin assay. Aspirin appears to be markedly less active in chronic inflammation than in acute. This finding is consistent with both experimental and clinical observations.

Relative potency in nonsimilar dose–response curves

Weed Science ◽  
2006 ◽  
Vol 54 (3) ◽  
pp. 407-412 ◽  
Author(s):  
Christian Ritz ◽  
Nina Cedergreen ◽  
Jens Erik Jensen ◽  
Jens Carl Streibig
Keyword(s):  
Dose Response ◽  
Relative Potency ◽  
Response Curves ◽  
Dose Response Curves

Dose-response Curves in the Fibrin Plate Assay Fibrinolytic Activity of Proteases

1974 ◽  
Vol 32 (02/03) ◽  
pp. 356-365 ◽  
Author(s):  
F Haverkate ◽  
D. W Traas
Keyword(s):  
Dose Response ◽  
Fibrinolytic Activity ◽  
Enzyme Concentration ◽  
Response Curves ◽  
Agar Gel ◽  
Porcine Tissue ◽  
Plate Assay ◽  
Fibrin Plate ◽  
Different Types ◽  
Dose Response Curves

SummaryIn the fibrin plate assay different types of relationships between the dose of applied proteolytic enzyme and the response have been previously reported. This study was undertaken to determine whether a generally valid relationship might exist.Trypsin, chymotrypsin, papain, the plasminogen activator urokinase and all of the microbial proteases investigated, including brinase gave a linear relationship between the logarithm of the enzyme concentration and the diameter of the circular lysed zone. A similar linearity of dose-response curves has frequently been found by investigators who used enzyme plate assays with substrates different from fibrin incorporated in an agar gel. Consequently, it seems that this linearity of dose-response curves is generally valid for the fibrin plate assay as well as for other enzyme plate bioassays.Both human plasmin and porcine tissue activator of plasminogen showed deviations from linearity of semi-logarithmic dose-response curves in the fibrin plate assay.

BIOASSAY OF THYROID HORMONE USING HYPOTHYROID TADPOLES

1962 ◽  
Vol 41 (1) ◽  
pp. 143-153 ◽  
Author(s):  
U. Henriques
Keyword(s):  
Thyroid Hormone ◽  
Dose Response ◽  
Developmental Rate ◽  
Response Curves ◽  
Sodium Salts ◽  
Dose Response Curves

ABSTRACT A bioassay of thyroid hormone has been developed using Xenopus larvae made hypothyroid by the administration of thiourea. Only tadpoles of uniform developmental rate were used. Thiourea was given just before the metamorphotic climax in concentrations that produced neoteni in an early metamorphotic stage. During maintained thiourea neotoni, 1-thyroxine and 1-triiodothyronine were added as sodium salts to the water for three days and at the end of one week the stage of metamorphosis produced was determined. In this way identical dose-response curves were obtained for the two compounds. No qualitative differences between their effects were noted except that triiodothyronine seemed more toxic than thyroxine in equivalent doses. Triiodothyronine was found to be 7–12 times as active as thyroxine.

Dose Response Curves for Microwave Ablation in the Cardioplegia-Arrested Porcine Heart

2005 ◽  
Vol 8 (4) ◽  
pp. E269-E274 ◽  
Author(s):  
Sydney L. Gaynor ◽  
Gregory D. Byrd ◽  
Michael D. Diodato ◽  
Yosuke Ishii ◽  
Anson M. Lee ◽  
...  
Keyword(s):  
Dose Response ◽  
Microwave Ablation ◽  
Response Curves ◽  
Porcine Heart ◽  
Dose Response Curves

Modeling Nonmonotonic Dose-Response Curves

2001 ◽  
Author(s):  
Quinton J. Nottingham ◽  
Jeffrey B. Birch ◽  
Barry A. Bodt
Keyword(s):  
Dose Response ◽  
Response Curves ◽  
Dose Response Curves

scholarly journals Comment Concerning the Effects of Light Intensity on Melatonin Suppression in the Review “Light Modulation of Human Clocks, Wake, and Sleep” by A. Prayag et al.

2021 ◽  
Vol 3 (1) ◽  
pp. 181-188
Author(s):  
Peter Bracke ◽  
Eowyn Van de Putte ◽  
Wouter R. Ryckaert
Keyword(s):  
Phase Shift ◽  
Light Intensity ◽  
Dose Response ◽  
Light Modulation ◽  
Response Curves ◽  
Practical Applications ◽  
Circadian Phase ◽  
Melatonin Suppression ◽  
Dose Response Curves ◽  
Circadian Phase Shift

Dose-response curves for circadian phase shift and melatonin suppression in relation to white or monochromatic nighttime illumination can be scaled to melanopic weighed illumination for normally constricted pupils, which makes them easier to interpret and compare. This is helpful for a practical applications.

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