Selection of Dose Levels for Estimating a Percentage Point of a Logistic Quantal Response Curve

1980 ◽  
Vol 29 (1) ◽  
pp. 25 ◽  
Author(s):  
Robert K. Tsutkawa
Keyword(s):  
Response Curve ◽  
Quantal Response ◽  
Dose Levels ◽  
Selection Of

ANTI-OVULATORY ACTIVITY OF STEROIDS ADMINISTERED BY GAVAGE IN THE ADULT OESTRUS RABBIT

1963 ◽  
Vol 42 (2_Suppl) ◽  
pp. S17-S30
Author(s):  
Fred A. Kind ◽  
Ralph I. Dorfman
Keyword(s):  
Dose Response ◽  
Active Compound ◽  
Subcutaneous Injection ◽  
Response Curve ◽  
Parent Compound ◽  
Dose Response Curve ◽  
Relative Potency ◽  
Reference Standard ◽  
Highly Active ◽  
Dose Levels

ABSTRACT Thirty-seven steroids have been studied as orally effective inhibitors of ovulation in the mated oestrus rabbit. Norethisterone served as the reference standard and a dose response curve was established between the 0.31 and 1.25 mg dose levels. Nine highly active anti-ovulatory compounds are described listed in a decreasing order of potency with norethisterone having the arbitrary value of one: 6-chloro-Δ6-dehydro-17α-acetoxyprogesterone (35), 6α-methyl-Δ1-dehydro-17α-acetoxyprogesterone (≥ 10), 6-fluoro-Δ6-dehydro-17α-acetoxyprogesterone(9), 6-methyl-Δ6-dehydro-17α-acetoxyprogesterone (5), Δ6-dehydro-17α-acetoxyprogesterone (≥ 3), 6α-methyl-17α-acetoxyprogesterone (2.6), 6-chloro-Δ1,6-bisdehydro-17α-acetoxyprogesterone (≥ 2), 2-hydroxymethyl-17α-methyl-17β-hydroxyandrostan-3-one (≥ 2), and 6α-fluoro-16α-methyl-17α-acetoxyprogesterone (≥ 1.25). The anti-ovulatory activity of a compound was not related necessarily to the progestational activity of a compound nor to the anti-gonadotrophic activity as measured in parabiotic rats. 6-Chloro-Δ60dehydro-17-acetoxyprogesterone was as effective by gavage as previously shown by subcutaneous injection. 2-Hydroxymethyl-17α-methyl-17β-hydroxyandrostan-3-one was at least 2.5 times more active by gavage than by injection. While 17α-acetoxyprogesterone was a very weak anti-ovulatory steroid, modifications of the structure by addition of methyl or halogen at the 6α position with or without unsaturation greatly increased the activity. 6-Chloro-Δ6-dehydro-27α-acetoxyprogesterone was the most active compound in this series showing a relative potency of 3500 times that of the parent compound 17α-acetoxyprogesterone.

scholarly journals Resistance to Glyphosate in Populations of Digitaria insularis

2018 ◽  
Vol 36 ◽  
Author(s):  
N.V. COSTA ◽  
G. MORATELLI ◽  
S.D. FERREIRA ◽  
A.C. SALVALAGGIO ◽  
A.C.P. RODRIGUES-COSTA
Keyword(s):  
Experimental Design ◽  
Response Curve ◽  
Glyphosate Resistance ◽  
No Tillage ◽  
Agronomic Practices ◽  
Intensive Use ◽  
Tillage System ◽  
Moderate Resistance ◽  
Agricultural Areas ◽  
Selection Of

ABSTRACT: The intensive use of glyphosate can select resistant populations. This study aimed at evaluating the occurrence of glyphosate resistance in populations of D. insularis in agricultural areas. Three experiments were conducted in randomized block experimental design with four replications. The Resistance Degree (RD) was determined by a dose-response curve in the evaluated populations: Experiment 2012, São Camilo (R01 and R02) and Palotina (R03, R04 and S05-susceptible); Experiment 2013 Palotina (R06 and R12), Katueté/Paraguay (R07), Toledo (R08 and R10), Cascavel (R09), São Miguel do Iguaçu (R11), Dom Eliseu/Pará (S13-susceptible); Experiment 2015 Nova Aurora (R14), Iracema do Oeste (R15 and R16), Jesuitas (R17 and R18), Tupãssi (R19), Jotaesse (R20), Espigão Azul (R21) and Palmitopolis (S22- susceptible). In 2012, it was possible to confirm a moderate resistance (RD = 1.1 to 5.0) only in R03; and populations R01, R02 and R04 were highly resistant (RD>5.0). In 2013, populations R09, R10, R11 and R12 showed resistance, while R06, R07 and R08 were highly resistant. In 2015, the R14, R16, R18, R19 and R20 populations showed moderateresistance, and R15 and R18 were highly resistant. Only R21 was susceptible. It was found that 83% of producers use the no-tillage system, 100% use the succession soybean/corn with 90% transgenic varieties, 45% of producers cannot explain the procedure regulation/sprayer calibration. Around 62% use practices to prevent the selection of resistant biotypes. Resistance was confirmed in 89.5% of the populations. The adopted agronomic practices may explain these results.

The Evidence for 20 mg a day of Fluoxetine as the Optimal Dose in the Treatment of Depression

1988 ◽  
Vol 153 (S3) ◽  
pp. 109-112 ◽  
Author(s):  
A. C. Altamura ◽  
S. A. Montgomery ◽  
J. F. Wernicke
Keyword(s):  
Tricyclic Antidepressants ◽  
Standard Dose ◽  
Optimal Dose ◽  
Serotonin Uptake Inhibitor ◽  
Treatment Of Depression ◽  
Equivalent Efficacy ◽  
Dosage Regime ◽  
Dose Ranging ◽  
Dose Levels ◽  
Selection Of

Fluoxetine, a selective serotonin-uptake inhibitor, has been shown to be effective in the treatment of depression. A series of studies found fluoxetine to be more effective than placebo and to be associated with equivalent efficacy to standard reference tricyclic antidepressants (Stark & Hardison, 1985; Feighner & Cohn, 1985).The selection of a dosage regime for fluoxetine in these studies was based on the information gathered from open dose-ranging investigations. In these studies, treatment starts with one dose level, which is then increased as indicated in the protocol or until increased doses are not tolerated due to side-effects. One of the weaknesses in this method of choosing the likely standard dose of a new antidepressant lies in the inherent bias towards the selection of the higher dose levels. This is particularly true for drugs which are well tolerated.

scholarly journals Use of Severity Grades to Characterize Histopathologic Changes

2018 ◽  
Vol 46 (3) ◽  
pp. 256-265 ◽  
Author(s):  
Kenneth A. Schafer ◽  
John Eighmy ◽  
James D. Fikes ◽  
Wendy G. Halpern ◽  
Renee R. Hukkanen ◽  
...  
Keyword(s):  
Working Group ◽  
Pathology Report ◽  
Morphologic Change ◽  
Severity Grade ◽  
Hazard Characterization ◽  
Histopathologic Diagnosis ◽  
Regulatory Submissions ◽  
Dose Levels ◽  
Grading Scales ◽  
Selection Of

The severity grade is an important component of a histopathologic diagnosis in a nonclinical toxicity study that helps distinguish treatment-related effects from background findings and aids in determining adverse dose levels during hazard characterization. Severity grades should be assigned based only on the extent (i.e., amount and complexity) of the morphologic change in the examined tissue section(s) and be clearly defined in the pathology report for critical lesions impacting study interpretation. However, the level of detail provided and criteria by which severity grades are assigned can vary, which can lead to inappropriate comparisons and confusion when evaluating pathology results. To help address this issue, a Working Group of the Society of Toxicologic Pathology’s Scientific and Regulatory Policy Committee was formed to provide a “points to consider” article on the assignment and application of pathology severity grades. Overall, the Working Group supports greater transparency and consistency in the reporting of grading scales and provides recommendations to improve selection of diagnoses requiring more detailed severity criteria. This information should enhance the overall understanding by toxicologic pathologists, toxicologists, and regulatory reviewers of pathology findings and thereby improve effective communication in regulatory submissions.

The Estimation of Serum Fructosamine: An Alternative Measurement to Glycated Haemoglobin

1985 ◽  
Vol 22 (1) ◽  
pp. 84-89 ◽  
Author(s):  
E J Hindle ◽  
Glenise M Rostron ◽  
J A Gatt
Keyword(s):  
Serum Albumin ◽  
Response Curve ◽  
Glycated Haemoglobin ◽  
Oestrogen Therapy ◽  
Protein Status ◽  
Normal Ranges ◽  
Serum Fructosamine ◽  
Significant Difference ◽  
Alternative Measurement ◽  
Selection Of

A method is presented for the estimation of fructosamine using a Cobas Bio centrifugal analyser. The effect of three different preparations of human serum albumin used for construction of calibration curves of 1-deoxy-1-morpholinofructose is described. The selection of serum albumin and the concentration used in the standard solutions is critical since the dose-response curve is affected differently and will therefore influence the estimated values. Normal ranges were obtained for non-diabetic subjects with normal protein status and for a group of females with reduced albumin levels due to pregnancy or oestrogen therapy. There was no significant difference between fructosamine levels in these populations. Fructosamine was also estimated in 250 patients attending a diabetic out-patient department and this correlated well with haemoglobin A1 estimated simultaneously. The method is rapid, technically simple and inexpensive and may prove to be a useful and reliable alternative to HbA1 estimation.

scholarly journals The detection of variation in host susceptibility in dilution counting experiments

1956 ◽  
Vol 54 (3) ◽  
pp. 401-414 ◽  
Author(s):  
P. Armitage ◽  
C. C. Spicer
Keyword(s):  
Standard Deviation ◽  
Response Curve ◽  
Host Susceptibility ◽  
Quantal Response ◽  
Infection Rates ◽  
Response Curves ◽  
Response Data ◽  
Alternative Test ◽  
Tolerance Distribution ◽  
Better Than

Variation in host susceptibility results in flattening of the quantal response curve obtained in dilution counting experiments. This departure from the exponential curve obtained with uniform hosts is found primarily at the lower dilutions, where the infection rates are high. The test proposed by Moran, for the detection of host variability, may easily fail to detect quite appreciable heterogeneity with the numbers of observations that are likely to be available in practice. Examination of the response curves corresponding to various theoretical distributions of susceptibility suggests that detection of heterogeneity is unlikely unless the probability that a particle can initiate infection is distributed with a low mean and considerable positive skewness.The problem is related to that of estimating the standard deviation of a tolerance distribution from quantal response data. This suggests an alternative test, based on the Spearman-Kärber method, which, however, appears to be no better than Moran's test. Both methods provide estimates of the variability of the susceptibility distribution.

scholarly journals STUDIES ON THE PATHOGENESIS OF FEVER

1963 ◽  
Vol 117 (3) ◽  
pp. 349-364 ◽  
Author(s):  
Donald L. Bornstein ◽  
Carl Bredenberg ◽  
W. Barry Wood
Keyword(s):  
Dose Response ◽  
Response Curve ◽  
Dose Response Curve ◽  
Febrile Reaction ◽  
Low Concentrations ◽  
Constant Rate ◽  
Trained Individual ◽  
Small Doses ◽  
Dose Levels ◽  
Secondary Rise

Although the absolute febrile responses of trained individual rabbits injected intravenously with small to moderate doses of leucocytic pyrogen vary over an appreciable range, the relative responses of each rabbit to changes in dosage are satisfactorily reproducible. The quantitative dose-response relationship is characterized by a hyperthermic ceiling at which the intensity of the febrile reaction is relatively constant over a wide dosage range. Only at lower dose levels, where the dose-response curve is reasonably steep, is the magnitude of the fever produced proportional to the amount of pyrogen injected. When sufficiently large doses of LP are injected, the hyperthermic ceiling is exceeded. The fevers thus induced are biphasic in character and, in this way, resemble the usual response to bacterial endotoxin. Similar biphasic fevers result from continuous infusions of relatively low concentrations of LP at a constant rate. Repeated intermittent injections of moderate doses of LP likewise cause prolonged biphasic fevers, but, once the fever has become established, the reaction to each individual injection becomes markedly depressed. When large doses of LP are injected at daily intervals, the characteristic biphasic response occurs only following the first injection. Thereafter a state of tolerance intervenes in which the late secondary rise in temperature fails to occur. This form of tolerance lasts as long as the daily injections are continued but subsides within a few days after the injections are stopped. During the transient tolerance the rabbit's responsiveness to small doses of LP (in the sensitive range of the dose response curve) is depressed. In addition, the amount of endogenous pyrogen mobilized from the tissues by a large dose of LP is not as great as that generated in a normal rabbit. The relations of these findings to biphasic fevers, tolerance, and the accuracy of the conventional method of pyrogen assay are briefly discussed.

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