Tumorigenicity of minute dose levels of N-methyl-N-formylhydrazine of Gyromitra esculenta

1982 ◽  
Vol 78 (1) ◽  
pp. 11-16 ◽  
Author(s):  
B. Toth ◽  
K. Patil
Keyword(s):  
Dose Levels ◽  
Minute Dose

Intraneuronal accumulations of lysosomes in the cerebellum of rats and dogs after dosing with MDL-832

1990 ◽  
Vol 48 (3) ◽  
pp. 830-831
Author(s):  
S.D. Barnard ◽  
S.D. Warner
Keyword(s):  
Brown Pigment ◽  
Beagle Dogs ◽  
Sprague Dawley ◽  
Gelatin Capsules ◽  
Pigment Granules ◽  
Sprague Dawley Rats ◽  
Hematoxylin And Eosin ◽  
Dose Levels

1, 2, 9, 10-tetramethoxyaporphine phosphate (MDL-832) was once considered a potential human antitussive. MDL-832 was administered orally in the diets of Sprague-Dawley rats at dose levels of 0, 5, 10, 20, 40, 80 and 160 mg/kg/day for 3 and 6 months and in gelatin capsules to Beagle dogs at 0, 5, 10, 15, 30 and 60 mg/kg/day for 3, 6 and 12 months. Histopathologic examinations of hematoxylin and eosin-stained cerebellar sections revealed intracytoplasmic brown pigment accumulations in large fusiform neurons (presumably the motor type) of the pons. The pigment granules were found to be PAS-positive, non-acid fast, iron-free, Sudan B-positive and fuchsinophilic. Intraneuronal pigment accumulations were seen in rats after 3 months of treatment at 80 mg but not at 40 mg and after 6 months at 20 mg but not at 10 mg. For dogs the effect was observed after 3 months at 60 mg but not at 30 mg and after 12 months at 10 mg but not at 5 mg.

Evaluation of two link GAT-1 trainer tasks by experienced pilots at three alcohol dose levels

1974 ◽  
Author(s):  
Peter H. Henry ◽  
Thomas Q. Davis ◽  
Edward J. Engelken ◽  
Richard C. McNee ◽  
Harold N. Keiser ◽  
...  
Keyword(s):  
Alcohol Dose ◽  
Dose Levels

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.

EFFECT OF OESTRONE-PELLET IMPLANTATION ON PLASMA LEVELS OF PROLACTIN

1970 ◽  
Vol 64 (2) ◽  
pp. 265-272 ◽  
Author(s):  
A. A. van der Gugten ◽  
M. Sala ◽  
H. G. Kwa
Keyword(s):  
Plasma Levels ◽  
Male Rats ◽  
Mean Values ◽  
The Mean ◽  
Dose Levels ◽  
Higher Doses ◽  
Primary Break

ABSTRACT Eight female and eight male rats were castrated at the age of 8 to 10 weeks. Four spayed and four orchidectomized rats received one oestrone/cholesterol pellet (200 μg oestrone) on the day of operation (day 0), a second pellet on day 11 and a third on day 23. The remaining animals received four oestrone/cholesterol pellets at these times. The fluctuations in the prolactin levels in the circulation induced by the oestrogen challenges in these animals were followed during 31 days by radioimmunoassays performed on days 3, 7, 9, 14, 15, 17, 23, 24, 25, 28 and 31. The results suggested that the homoeostatic mechanism regulating plasma levels of prolactin was capable of withstanding the three time-spaced oestrogen challenges only in the spayed animals receiving the lower doses of oestrogen, since it allowed the mean values of the prolactin levels to remain fairly constant during the first 4 weeks. The levels in this group rose to much higher levels only on day 31. The higher doses of oestrone in the spayed rats and both dose levels of oestrone in the orchidectomized animals apparently resulted in a primary break-down of the homoeostatic mechanism, since the prolactin levels in the animals of these groups rose to much higher levels either on day 7 or on day 9. This was followed by a period during which the prolactin levels appeared to be more or less under control, until a second and probably definitive failure of the homoeostatic mechanism allowed the mean levels to rise sharply again.

SIMPLIFIED MATHEMATICS FOR MULTIPLE BIOASSAYS

1960 ◽  
Vol XXXV (III) ◽  
pp. 454-468 ◽  
Author(s):  
R. Borth
Keyword(s):  
Parallel Line ◽  
Numerical Example ◽  
Dose Levels

ABSTRACT Gaddum's simplified system of computation for the analysis of biological parallel-line assays is extended to the assay of several unknown preparations simultaneously against the same standard, using up to four dose levels of each preparation. Complete working directions and formulae are provided and illustrated by a numerical example. Limiting conditions are briefly discussed.

STUDIES ON SULFATION FACTOR (SF) ACTIVITY OF HUMAN SERUM

1960 ◽  
Vol XXXV (III) ◽  
pp. 381-396 ◽  
Author(s):  
Sven Almqvist
Keyword(s):  
Human Serum ◽  
Normal Serum ◽  
Treatment Level ◽  
Response Curves ◽  
Normal Children ◽  
Significant Difference ◽  
Human Sera ◽  
Normal Humans ◽  
Pre Treatment ◽  
Dose Levels

ABSTRACT The sulfation factor (SF) activity of human sera has been estimated using a modification of the method of Daughaday et al. (1959). Each assay was statistically evaluated. The method had a mean precision of 0.14 and, used as an assay of GH of human serum, a sensitivity in three pituitary dwarfs of 0.1 to 0.6 μg of HGH/ml of serum. SF activity was found at all ages between 1 month and 75 years. There was a significantly lower mean SF activity below the age of half a year. Three cases of pituitary dwarfism had significantly low SF activities of sera. There was no significant difference between the SF activities of sera from untreated pituitary dwarfs and the sera from normal children below half a year of age. Dose-response curves with large volumes of sera from pituitary dwarfs and small volumes of sera from normal humans had the same slopes. Four mg of HGH prepared according to the method of Li & Papkoff (1956) resulted in a normal serum SF activity in each of the three dwarfs. A significant (P < 0.01) linear relationship was found between the concentration of SF activity of sera from these subjects and the logarithm of the dose of HGH given with dose levels of 1, 2 and 4 mg daily for three days. The decline of serum SF activity to the pre-treatment level following HGH in one dwarf suggested a half life not different from that indicated by others for growth hormone.

The Natural Radioactivity in Food: A Comparison Between Different Feeding Regimes

2019 ◽  
Vol 15 (5) ◽  
pp. 493-499 ◽  
Author(s):  
Francesco Caridi ◽  
Santina Marguccio ◽  
Alberto Belvedere ◽  
Maurizio D`Agostino ◽  
Giovanna Belmusto
Keyword(s):  
Vegetable Oils ◽  
Natural Radioactivity ◽  
Specific Activity ◽  
Mean Value ◽  
Vegetable Food ◽  
Fish Samples ◽  
Feeding Regimes ◽  
Italian Origin ◽  
Dose Levels

Background: In this article a comprehensive study was carried out for the determination of natural radioactivity in animal and vegetable food (meat, fish, milk and derivates, legumes, cereals and derivates, fruit, hortalizas, vegetables, vegetable oils) typical of different feeding regimes, for the age category higher than 17 years. Methods: A total of eighty-five samples of Italian origin, coming from large retailers during the years 2014, 2015 and 2016, were analyzed through HPGe gamma spectrometry. Results: The specific activity of 40K was investigated and its mean value was found to be: (106.3 ± 6.9) Bq/kg for bovine, swine and sheep meat; (116.5 ± 9.7) Bq/kg for fish; (52.9 ± 3.1) Bq/kg for milk and derivates; (271.9 ± 16.7) Bq/kg for legumes; (67.2 ± 4.7) Bq/kg for cereals and derivates; (52.7 ± 4.4) Bq/kg for fruit; (72.9 ± 5.6) Bq/kg for hortalizas; (83.9 ± 6.5) Bq/kg for vegetables; lower than the minimum detectable activity for vegetable oils. For animal food the highest mean 40K activity concentration was found in fish samples; for vegetable food the highest one was detected in legumes. Conclusion: The evaluation of dose levels due to the food ingestion typical of Mediterranean, Vegetarian and Vegan diets was performed. The annual effective dose was found to be 0.16 mSv/y, 0.41 mSv/y and 0.54 mSv/y, respectively.

All-trans retinoic acid: tolerance and biologic effects in myelodysplastic syndrome.

1993 ◽  
Vol 11 (8) ◽  
pp. 1489-1495 ◽  
Author(s):  
R Kurzrock ◽  
E Estey ◽  
M Talpaz
Keyword(s):  
Retinoic Acid ◽  
Side Effects ◽  
Myelodysplastic Syndrome ◽  
Acid Tolerance ◽  
Maximum Tolerated Dose ◽  
Significant Activity ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Biologic Effects ◽  
Dose Levels

PURPOSE We conducted a study to evaluate the tolerance to and biologic effects of all-trans retinoic acid in patients with myelodysplastic syndrome. PATIENTS AND METHODS Thirty-nine patients with myelodysplastic syndrome were treated with oral all-trans retinoic acid for 6 weeks. Dose levels were 10, 25, 50, 100, 150, 200, and 250 mg/m2/d. At least three patients were treated on each dose level. RESULTS The most common side effects were mucocutaneous dryness and erythema, and hypertriglyceridemia. Dose-limiting side effects were diverse and included dermatitic problems, sensorineural hearing loss, headaches, nausea and vomiting, myalgias, and dyspnea. The maximum-tolerated dose was 150 mg/m2/d. Only one response was seen among 29 patients considered assessable for response. CONCLUSION All-trans retinoic acid can be safely administered to patients at doses up to 150 mg/m2/d for 6 weeks. However, as administered in this study, this compound does not appear to have significant activity in myelodysplastic syndromes.

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