EFFECT OF BOVINE GROWTH HORMONE AND A PARTIALLY PURE PREPARATION OF SOMATOMEDIN ON VARIOUS GROWTH PARAMETERS IN HYPOPITUITARY DWARF MICE

1981 ◽  
Vol 89 (2) ◽  
pp. 275-282 ◽  
Author(s):  
A. T. HOLDER ◽  
E. M. SPENCER ◽  
M. A. PREECE
Keyword(s):  
Body Weight ◽  
Growth Parameters ◽  
Costal Cartilage ◽  
Regression Line ◽  
Tail Length ◽  
Once Daily ◽  
Organ Weights ◽  
Dwarf Mice ◽  
Weight Velocity

The growth-promoting effects of a partially purified preparation of somatomedin (12·7 units/mg) were compared with those of various doses of bovine GH (5, 20 and 80 μg/day) when injected into hypopituitary dwarf mice. Growth parameters studied were body-weight and tail-length velocities (calculated as the slope of a regression line fitted to daily measurements against time), uptake of 35SO2−4 into costal cartilage in vivo and organ weights (heart, liver and kidney). In the first experiment somatomedin (6·4 units/day), bovine GH and 0·9% NaCl were injected once daily in a volume of 0·1 ml for 10 days. Treatment with bovine GH promoted a significant dose-dependent increase in body-weight and tail-length velocities and 35SO2−4 uptake into costal cartilage in vivo. Somatomedin also promoted a significant increase in body-weight velocity and 35SO2−4 uptake, both responses were between that observed with the lowest dose of bovine GH and control values. Somatomedin did not promote increase in tail-length velocity. Organ weights did not differ significantly between any of the treatment groups when expressed as mg/g body weight. In the second experiment somatomedin (a daily total of 21·6 units/day) and 0·9% NaCl were injected three times per day in a volume of 0·033 ml, bovine GH was again injected once daily in a volume of 0·1 ml, and the treatment period was 12 days. As in the first experiment all doses of bovine GH and somatomedin promoted a significant increase in body-weight velocity. These results are consistent with the somatomedin hypothesis.

Prolonged oestrogen treatment inhibits growth hormone-induced growth in hypopituitary dwarf mice

1983 ◽  
Vol 96 (3) ◽  
pp. 451-456 ◽  
Author(s):  
A. T. Holder ◽  
R. G. Clark ◽  
M. A. Preece
Keyword(s):  
Body Weight ◽  
Treatment Period ◽  
Costal Cartilage ◽  
Tail Length ◽  
Gh Treatment ◽  
Oestrogen Treatment ◽  
Dwarf Mice ◽  
Dose Dependent Increase ◽  
Dose Dependent

This paper presents an investigation into the effects of prolonged oestrogen treatment (20 days) on basal growth and on growth stimulated by GH in hypopituitary dwarf mice. Body 35SO42− weight and tail length were measured during the treatment period and uptake of S04 into costal cartilage in vivo at the end of the treatment period. This study confirmed that treatment with human GH promotes a dose-dependent increase in body weight, tail length and uptake of 35SO42− in vivo; there was a highly significant correlation between these responses. Treatment with oestrogen alone had no significant effect on any of the parameters measured. All groups receiving combined oestrogen and human GH treatment showed a significant increase in body weight and tail length compared with animals receiving the same dose of oestrogen alone. However, the increase in body weight and tail length was significantly less in animals given the highest dose of oestrogen plus human GH than that observed in animals treated with the same dose of human GH alone. Treatment with oestrogen had no significant effect on the uptake of 35SO42− stimulated by human GH. Possible mechanisms for the growth-inhibiting effects of oestrogens are discussed.

EFFECTS OF GROWTH HORMONE, PROLACTIN AND THYROXINE ON BODY WEIGHT, SOMATOMEDIN-LIKE ACTIVITY AND IN-VIVO SULPHATION OF CARTILAGE IN HYPOPITUITARY DWARF MICE

1980 ◽  
Vol 85 (1) ◽  
pp. 35-47 ◽  
Author(s):  
A. T. HOLDER ◽  
M. WALLIS ◽  
P. BIGGS ◽  
M. A. PREECE
Keyword(s):  
Growth Hormone ◽  
Costal Cartilage ◽  
Tail Length ◽  
Bovine Growth Hormone ◽  
Dwarf Mouse ◽  
Dwarf Mice ◽  
Dose Dependent Increase ◽  
Dose Dependent ◽  
In Vivo Uptake

SUMMARY Hypopituitary dwarf mice were found to have reduced levels of serum somatomedin-like activity compared with normal mice of the Snell strain. Treatment with bovine growth hormone for 3 and 7 days resulted in growth without significantly increased levels of serum somatomedin-like activity, as detected by in-vitro uptake of 35SO42− into normal rat cartilage; only after treatment for 14 days was somatomedin activity significantly raised. However, treatment for 2 days with bovine growth hormone, bovine prolactin or thyroxine resulted in a dose-dependent increase in in-vivo uptake of 35SO42− into dwarf mouse costal cartilage; growth hormone and thyroxine did not act synergistically. Ten days of treatment with growth hormone promoted a dose-dependent increase in both growth (increased weight gain and tail length) and in-vivo uptake of 35SO42−. Increase in tail length was correlated with uptake of 35SO42−. Thus, in-vivo uptake of 35SO42− into dwarf mouse costal cartilage provides a sensitive method for detecting a dose-related effect of growth hormone.

EFFECT OF AGE, SEX, STARVATION, HYPOPHYSECTOMY AND GROWTH HORMONE FROM SEVERAL SPECIES ON THE INORGANIC SULPHATE POOL AND ON THE INCORPORATION IN VIVO OF SULPHATE INTO MOUSE COSTAL CARTILAGE

1971 ◽  
Vol 66 (2) ◽  
pp. 333-351 ◽  
Author(s):  
Georg Herbai
Keyword(s):  
Costal Cartilage ◽  
Time Lag ◽  
Cartilage Sample ◽  
Female Mice ◽  
Inorganic Sulphate ◽  
Isotope Technique ◽  
Disappearance Curve ◽  
The Individual ◽  
Dwarf Mice

ABSTRACT The influence of several conditions on sulphate incorporation into costal cartilage was investigated in mice of the N.M.R.I.-strain and in dwarfmice (dw/dw) by a new double isotope technique. The method permits estimation of sulphate incorporation into costal cartilage in vivo after correction for the size of the exchangeable inorganic sulphate pool of the individual animal. Detoxication to phenyl sulphate of injected phenol, following an injection of 3H-phenol and 35S-sulphate into the mice, allows determination of the sulphate pool. The incorporation rate of sulphate is expressed in ng, and includes all SO4 which had been incorporated in vivo into 5 pairs of cartilaginous ribs including their osteochondral junctions during 30 minutes. Sulphation rate was rather constant in growing female mice between 3 and 8 weeks age and then decreased markedly. Growing male mice exhibited an increase of sulphation activity until an age of 5 weeks and then a gradual decrease, similar to that of the females. Growth rates of both sexes were positively correlated with sulphate uptake activities. The form of the disappearance curve of incorporated sulphate suggested that the standard cartilage sample includes regions with different sulphate-metabolizing activities. Hypophysectomy resulted in a decrease of sulphation rate to a level about 30% of the control values, which was constant for several weeks. Starvation of the animals likewise depressed the sulphation rate and after 72 hours starvation the values became similar to those after hypophysectomy. Dwarf mice had much lower sulphation activities than their heterozygous controls. Neither bovine GH nor human GH elevated the low sulphation activity of hypophysectomized mice but porcine and ovine GH-preparations had a pronounced and dose-dependent effect. Normal growing male and female mice showed no response to large doses of ovine GH. Ear, xiphoid and tracheal cartilage from hypophysectomized animals behaved as costal cartilage with respect to the reduction in sulphation rate, but GH restored the sulphation values to normal only in costal cartilage. A single dose of 1 mg ovine GH given to hypophysectomized mice at different times in relation to the sulphation experiment increased sulphate incorporation only after a time lag of more than 8 but less than 17 hours after injection of GH, whose effect lasted at least 38 hours.

Studies of the Toxicological Potential of Tripeptides (L-Valyl-L-prolyl-L-proline and L-lsoleucyl-L-prolyl-L-proline): V. A 13-Week Toxicity Study of Tripeptides-Containing Casein Hydrolysate in Male and Female Rats

2005 ◽  
Vol 24 (4_suppl) ◽  
pp. 41-59 ◽  
Author(s):  
Seiichi Mizuno ◽  
John H. Mennear ◽  
Keiichi Matsuura ◽  
Bruce K. Bernard
Keyword(s):  
Body Weight ◽  
Food Consumption ◽  
Low Dose ◽  
Clinical Signs ◽  
Casein Hydrolysate ◽  
Toxicity Study ◽  
Once Daily ◽  
Organ Weights ◽  
Test Article ◽  
Weight Gains

The objective of this multiple-dose toxicity study was to assess the toxicological potential of two tripeptides, L-valyl-L-prolyl-L-proline (VPP) and L-isoleucyl-L-prolyl-L-proline (IPP), when administered once daily for 91 consecutive days to rats. The test article, powdered casein hydrolysate (CH) known to contain 0.6% VPP plus IPP, was prepared using Aspergillus oryzae protease. Prior to administration to the rats by oral gavage, the test article was suspended in sterile water. Groups of 12 male and 12 female Charles River rats were administered once daily doses of 0, 40, 200, or 1000 mg of CH (0, 0.2,1.2, or 6 mg VPP plus IPP/kg body weight [BW]). Antemortem evaluative parameters included gross observations of behavior and clinical signs; food consumption and body weight gains; ophthalmologic examinations; clinical pathology (hematology, clinical chemistry); and urinalysis. Postmortem parameters included determination of absolute and relative (to fasting body weight) organ weights and histopathological evaluation of approximately 50 organs and tissues from each animal. All rats survived until the scheduled termination of the study and no treatment-related clinical signs were observed. Food consumption was unaffected by administration of CH. All animals gained weight and there were no statistical differences between groups with respect to weight gains. There were no meaningful changes in hematological or coagulation parameters. Mid- and high-dose males (but not females) had slightly (<2%) increased mean serum chloride concentrations, but because the difference was so small and it was observed in only one sex, the authors considered its association with CH administration to be doubtful. Urinalysis revealed the occasional presence of crystals, leukocytes, and epithelial cells in animals from all experimental groups. Similarly, ophthalmic changes (lenticular clouding) were observed in both control and dosed animals. Mean relative (to body weight) kidney weight was decreased by 8 % in low-dose males and mean relative uterus weight was elevated 46 % in low-dose females. Absolute organ weights were not affected. Only naturally occurring microscopic changes were observed in all groups and none could be attributed to CH administration. It was concluded that, under the conditions of these experiments, the maximally tolerated dose (MTD) and the no-observable-effect level (NOEL) for powdered CH administered once daily for 13 weeks was greater than 1000 mg/kg BW/day or greater than 6 mg of VPP plus IPP/kg BW/day. There was no evidence of target organ toxicity associated with administration of the tripeptides. This corresponds to an margin of safety (MOS) of 60 based upon current thinking regarding incorporation in food.

scholarly journals Comparison of Sulfate Metabolism in Costal Cartilage of Normal and 'Little' Mice

1983 ◽  
Vol 36 (3) ◽  
pp. 263 ◽  
Author(s):  
NeiI M McKern
Keyword(s):  
Growth Hormone ◽  
Growth Rate ◽  
Body Weight ◽  
Costal Cartilage ◽  
Cartilage Degradation ◽  
Skeletal Growth ◽  
Sulfate Uptake ◽  
Sulfate Metabolism ◽  
C 50

C57BL/6J and mutant 'little' (lit/lit) mice c. 50 days of age were injected with doses of [35S]sulfate proportional to their body weight. Despite the diminished growth rate of lit/lit mice compared with normal mice at this age, uptake of radioactivity per unit mass of cartilage was similar for both mouse types, confirming previous data. Additional experiments with these mice established that the similarity of sulfate uptake could not be accounted for by differences in the location of bound sulfate or (for females) by differences in cartilage cellularity. Investigation of sulfate loss by costal cartilage in vivo indicated that cartilage degradation occurred at a greater rate in lit/lit mice than in normally growing mice. These latter data suggest that growth hormone, which is lacking in lit/lit mice, may in part regulate skeletal growth (at least for female mice) by inhibiting degradation of cartilage.

3,5-Di-iodo-l-thyronine suppresses TSH in rats in vivo and in rat pituitary fragments in vitro

1995 ◽  
Vol 145 (2) ◽  
pp. 291-297 ◽  
Author(s):  
C Horst ◽  
A Harneit ◽  
H J Seitz ◽  
H Rokos
Keyword(s):  
Body Weight ◽  
Significant Influence ◽  
Suppressive Effect ◽  
Feedback Mechanism ◽  
Organ Weights ◽  
Negative Feedback Mechanism ◽  
Rat Pituitary ◽  
Tsh Secretion

Abstract 3,5-Di-iodo-l-thyronine (T2) is a naturally occurring metabolite of thyroxine (T4). Contrary to earlier findings, T2 has recently been shown to have rapid effects in rat liver and in mononuclear blood cells. In the experiments described here, T2 was tested to determine whether it has a TSH suppressive effect in rats in vivo and in rat pituitary fragments in vitro. In experiments over 2 weeks in rats in vivo, low doses of T2 (20–200 μg/100 g body weight per day) had no significant influence on body and organ weights, but significantly decreased TSH and T4 serum concentrations. At 200 μg/100 g per day, T2 suppressed TSH to 43% and T4 to 29% of control levels. At 1–15 μg/100 g per day, 3,5,3′-tri-iodo-l-thyronine (T3), used as a comparison to T2, had significant effects on TSH and T4 levels, and also on body weight. Fifteen μg T3/100 g per day decreased TSH to 44%, T4 to 25%, and body weight to 59% of control levels. In experiments over 3 months in rats in vivo, a low dose (25 μg/100 g per day) of T2 suppressed TSH to 60% and T4 to 57% of control levels and had no significant influence on other parameters. Conversely, 0·1 μg/100 g per day T3 had significant effects on body and organ weights as well as pellet intake, but a less pronounced TSH suppressive effect: TSH concentrations were unchanged and T4 concentrations were down to 80% of control values. In rat pituitary fragments in vitro, a clear suppression of TSH secretion after a TRH pulse was demonstrated. To summarise, T2 is a specific agonist in the negative feedback mechanism on TSH secretion at the pituitary level without other apparent thyromimetic effects. Journal of Endocrinology (1995) 145, 291–297

Organ-weights and body-composition in mice bred for many generations at – 3˚C

1965 ◽  
Vol 162 (989) ◽  
pp. 502-516 ◽  
Keyword(s):  
Body Weight ◽  
Small Intestine ◽  
Tail Length ◽  
Organ Weights ◽  
Laboratory Rats ◽  
Calcium And Phosphorus ◽  
Intracellular Changes ◽  
Old Mice ◽  
Control State ◽  
Selection Of

Three classes of highly inbred 16-week-old mice, of strain A 2 G / Tb , were studied: (i) controls, kept at 21 °C; (ii) ‘new stock’, of the first or second generations reared in a room kept at –3 °C; (iii) ‘old stock’, of the fourteenth generation reared at –3 °C. All were bred at the same time. The new - stock mice were lighter than the controls, their tails were shorter, and they (especially the females) had less fat. They contained more water, and less nitrogen and collagen. The males, but not the females, had less calcium and phosphorus. The heart, stomach and small intestine were heavier than in the controls, and the intestine was longer. Liver and kidneys, too, were heavier, but these differences were large only in the females. The shaved skin was lighter, but the hair, especially in the females, heavier. Gonad weights were lower. The spleen tended to be lighter, but varied greatly. Most of these differences from the controls resemble those seen in adult laboratory rats exposed to cold for a few weeks. The old stock , of both sexes, had almost the same body-weight as the controls, but re­sembled the new stock in tail-length: hence the effect of cold on growth of the tail was inde­pendent of body-weight. The old-stock males had more fat than the controls, while the females were intermediate between the controls and the new stock. The males contained less water than the controls; while in nitrogen, collagen, calcium and phosphorus they did not differ significantly. The tendency to return towards the control state was less marked in the females. In weights of stomach, intestine and liver the old-stock males again resembled the controls; and their kidneys were lighter . They had, however, longer intestines than the controls and, like the new stock, they had heavier hearts. Their skin was lighter but hair, heavier. The spleen was lighter. Except in their kidneys and spleen, the old-stock females resembled the new-stock females, rather than the controls. Since other work has shown that the old-stock females are more efficient mothers than the new-stock, the old-stock mice of both sexes were clearly better adapted to cold than the new. This may have been due to intracellular changes making individual tissues more efficient. The change in the old stock cannot be due to selection of favourable genotypes; it may be due to a cumulative maternal effect.

CARTILAGE RESPONSE TO PLASMA AND PLASMA SOMATOMEDIN ACTIVITY IN RATS RELATED TO GROWTH BEFORE AND AFTER BIRTH

1981 ◽  
Vol 90 (1) ◽  
pp. 133-142 ◽  
Author(s):  
D. J. HILL ◽  
S. J. ANDREWS ◽  
R. D. G. MILNER
Keyword(s):  
Body Weight ◽  
Costal Cartilage ◽  
Basal Medium ◽  
Tail Length ◽  
Rat Plasma ◽  
Neonatal Rat ◽  
Postnatal Life ◽  
Fetal Life ◽  
Adult Rats ◽  
Adult Rat

Cartilage response to plasma, plasma somatomedin activity, body weight and length were measured in rats from 15 days of fetal age to 37 days postnatally. The metabolic activity of costal cartilage was assessed by the incorporation of [35S]sulphate in basal medium and after stimulation by plasma. It was found that (a) A significant stimulation of isotope uptake above basal levels occurred in the presence of 15% standard adult rat plasma at every age studied. (b) The degree of stimulation, a measure of cartilage sensitivity to plasma growth factors, increased through the latter part of fetal life but fell after birth. A high degree of cartilage stimulation was seen on day 6 of postnatal life. (c) The changes in cartilage sensitivity and in the stimulated isotope uptake, resembled the changes observed in growth rate for body weight, nose–rump length and tail length. (d) Plasma somatomedin activity measured by the pig costal cartilage assay was low in the fetus and neonate but rose to adult values 9 days after birth. However, plasma from fetal or neonatal rats tested on cartilage from rats of the same age was equipotent to adult rat plasma. (e) Plasma from hypophysectomized adult rats had a low potency in stimulating isotope uptake by neonatal rat cartilage but was equipotent to normal adult rat plasma in its action on fetal cartilage. (f) The action of plasma from hypophysectomized rats on fetal cartilage was unaffected by dialysis but was destroyed by incubation with trypsin.

Effect of Hematoporphyrin « in Vivo » and « in Vitro » on ATPC+ Tumor Cells

1968 ◽  
Vol 54 (5) ◽  
pp. 361-368
Author(s):  
Giorgio Cittadini ◽  
Tommaso De Cata ◽  
Carlo Gubinelli
Keyword(s):  
Growth Rate ◽  
Weight Loss ◽  
Body Weight ◽  
Drug Toxicity ◽  
Body Weight Loss ◽  
Ascites Tumor ◽  
Once Daily ◽  
Fluid Interaction

ATPC+ ascites tumor transplants of different size were performed in NMRI mice. Hematoporphyrin chlorhydrate (Hp) was administered i.p. once daily during the seven days following transplantation. In the first series « in vivo » (1.9 x 106 cells; 0.1, 0.3, 0.9 mg of Hp), body weight, ascitogenic time (Tasc) and total ascitic volume (TV) were determined. Hematoporphyrin-treated animals showed, after the apprearance of the ascites, a body weight loss superior to controls, due to the drug toxicity caused by Hp vs. ascitic fluid interaction. Neither Tasc nor TV were significantly modified. In the second series « in vivo » (2.3 x 104 or 2.3 x 102 cells; 0.3 mg Hp), body weight loss was lower, Tasc was significantly increased and also the survival varied. In a third experiment ATPC+ cells were incubated « in vitro » with Hp in a range from 102 to 108 molecules/cell). No effect was observed on growth rate when the cells were transplanted into the host.

scholarly journals In Vitro and In Vivo Efficacies of T-3811ME (BMS-284756) against Mycoplasma pneumoniae

2001 ◽  
Vol 45 (1) ◽  
pp. 312-315 ◽  
Author(s):  
Masahiro Takahata ◽  
Masako Shimakura ◽  
Ritsuko Hori ◽  
Kazuo Kizawa ◽  
Yozo Todo ◽  
...  
Keyword(s):  
Body Weight ◽  
Mycoplasma Pneumoniae ◽  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
In Vitro Activity ◽  
Free Base ◽  
Once Daily ◽  
Viable Cells

ABSTRACT T-3811, the free base of T-3811ME (BMS-284756), a new des-F(6)-quinolone, showed a potent in vitro activity (MIC at which 90% of the isolates tested are inhibited [MIC90], 0.0313 μg/ml) against Mycoplasma pneumoniae. The MIC90 of T-3811 was 4-fold higher than that of clarithromycin but was 4- to 8-fold lower than those of trovafloxacin, gatifloxacin, gemifloxacin, and moxifloxacin and was 16- to 32-fold lower than those of levofloxacin, ciprofloxacin, and minocycline. In an experimental M. pneumoniae pneumonia model in hamsters, after the administration of T-3811ME (20 mg/kg of body weight as T-3811, once daily, orally) for 5 days, the reduction of viable cells of M. pneumoniae in bronchoalveolar lavage fluid was greater than those of trovafloxacin, levofloxacin, and clarithromycin (20 and 40 mg/kg, orally) (P < 0.05).

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