Long-latency growth-promoting activity of EGF when administered to mice at the neonatal stage

1987 ◽  
Vol 253 (3) ◽  
pp. E251-E254
Author(s):  
O. Imada ◽  
N. Hayashi ◽  
K. Masamoto ◽  
S. Kasuga ◽  
T. Fuwa ◽  
...  
Keyword(s):  
Body Weight ◽  
Body Weight Gain ◽  
Daily Administration ◽  
Long Latency ◽  
Neonatal Stage ◽  
Epidermal Growth ◽  
Males And Females ◽  
Accelerated Growth ◽  
Dose Dependent Increase ◽  
Dose Dependent

The effect of biosynthetic human epidermal growth factor (Bh-EGF) as well as mouse EGF on postnatal development of mice of ICR strain was examined. Daily administration of Bh-EGF (0.01, 0.1, and 1.0 microgram X g body wt-1 X day-1) for 30 consecutive days postpartum caused a clearly dose-dependent increase in their body weight. Furthermore, in addition to the well-known premature eyelid opening and early tooth eruption, we have also observed precocious opening of the vagina among treated females. As far as the accelerated growth rate as reflected in their body weight gain was concerned, daily administration for only five consecutive days postpartum was just as effective as the above noted 30 consecutive daily injections. As to the precocious vaginal opening, however, the susceptible 5-day-period was found to be 14-18 days after the parturition. Some of those treated females also entered the estrous cycle precociously, a few days after the precocious opening of their vagina. The microscopic examination of various organs from treated males and females revealed no apparent pathological changes. As far as the above noted effects of EGF were concerned, Bh-EGF, which is xenogenic to mice, was as potent as mouse EGF.

Short-Term Toxicity (1 and 10 Days) of Cadmium Chloride in Male and Female Rats: Gavage and Drinking Water

1989 ◽  
Vol 8 (2) ◽  
pp. 377-404 ◽  
Author(s):  
Joseph F. Borzelleca ◽  
Elizabeth C. Clarke ◽  
L. W. Condie
Keyword(s):  
Drinking Water ◽  
Body Weight ◽  
Weight Gain ◽  
Body Weight Gain ◽  
Female Rats ◽  
Testicular Atrophy ◽  
Dependent Manner ◽  
Male And Female ◽  
Males And Females ◽  
Dose Dependent

Male and female Sprague-Dawley-derived rats received CdCl2 by gavage at doses of 25, 51, 107, and 225 mg CdCl2 per kg body weight per day for 1 or 10 consecutive days or in drinking solutions at concentrations of 13–323 mg CdCl2 per liter for 10 consecutive days. There were appropriate controls. In the 1 day study in males only, an apparent treatment-related but not statistically significant decrease in body weight was reported; spleen weights and ratios were significantly lower and lung weights and ratios were significantly higher (in the highest dose only). Dose-dependent mortality was observed in the 10 day gavage study. Body weight gain was depressed in a dose-dependent manner in both males and females. Weights and/or ratios of brain, liver, spleen, lungs, thymus, kidneys, and testes of treated males were depressed in a dose-dependent manner. In females, weights and/or ratios of liver, spleen, thymus, and kidneys were depressed in a dose-dependent manner. Focal necrotic changes in renal tubular epithelium and tubular degeneration were reported in males and females. Testicular and hepatic histopathologic changes (testicular atrophy and necrosis and hepatic necrosis) were also reported in males. In the drinking water study, males demonstrated dose-dependent decreases in body weight gain and weight and/or ratios of liver, spleen, thymus, and kidneys. There were no significant compound-related effects in females, although liver weights and ratios were lower. There were no compound-related histopathologic effects.

Increased Urinary Excretion of Carnitine and Acylcarnitine by Mercuric Chloride Is Reversed by 2,3-Dimercapto-1-Propanesulfonic Acid in Rats

2010 ◽  
Vol 29 (3) ◽  
pp. 313-317
Author(s):  
Waleed A. Al-Madani ◽  
Nikhat J. Siddiqi ◽  
Abdullah S. Alhomida ◽  
Haseeb A. Khan ◽  
Ibrahim A. Arif ◽  
...  
Keyword(s):  
Body Weight ◽  
Urinary Excretion ◽  
Mercuric Chloride ◽  
Free Carnitine ◽  
Male Rats ◽  
Significant Protection ◽  
Total Carnitine ◽  
Dose Dependent Increase ◽  
Dose Dependent ◽  
Wistar Male Rats

This investigation was aimed to study the effect of 2,3-dimercapto-1-propanesulfonic acid (DMPS) on mercuric chloride (HgCl2)-induced alterations in urinary excretion of various carnitine fractions including free carnitine (FC), acylcarnitine (AC), and total carnitine (TC). Different groups of Wistar male rats were treated with HgCl2 at the doses of 0.1, 0.5, 1.0, 2.0, and 3.0 mg/kg body weight, and the animals were sacrificed at 24 hours following HgCl2 injection. A separate batch of animals received HgCl2 (2 mg/kg) with or without DMPS (100 mg/kg) and sacrificed at 24 or 48 hours after dosing. Administration of HgCl2 resulted in statistically significant and dose-dependent increase in the urinary excretion of FC, AC, and TC in rats. However, the ratio of urinary AC:FC was significantly decreased by HgCl2. Pretreatment with DMPS offered statistically significant protection against HgCl2-induced alterations in various urinary carnitine fractions in rats.

scholarly journals Dietary Whole Egg Reduces Body Weight Gain in a Dose-Dependent Manner in Zucker Diabetic Fatty Rats

2019 ◽  
Vol 149 (10) ◽  
pp. 1766-1775 ◽  
Author(s):  
Cassondra J Saande ◽  
Joseph L Webb ◽  
Paige E Curry ◽  
Matthew J Rowling ◽  
Kevin L Schalinske
Keyword(s):  
Vitamin D ◽  
Body Weight ◽  
Weight Gain ◽  
Body Weight Gain ◽  
Dependent Manner ◽  
Dietary Recommendations ◽  
Zucker Diabetic Fatty Rats ◽  
Zdf Rats ◽  
Dose Dependent ◽  
Whole Egg

ABSTRACT Background We previously reported that a whole-egg–based diet attenuated weight gain in rats with type 2 diabetes (T2D) and more effectively maintained vitamin D status than an equivalent amount of supplemental cholecalciferol. Objectives The objective of this study was to determine the lowest dose of whole egg effective at maintaining vitamin D homeostasis and attenuating the obese phenotype in T2D rats. Methods Zucker diabetic fatty (ZDF) rats (n = 40; age 6 wk; prediabetic) and their lean controls (n = 40; age 6 wk) were randomly assigned to a diet containing 20% casein (CAS) or 20%, 10%, 5%, or 2.5% protein from whole egg (20% EGG, 10% EGG, 5% EGG, and 2.5% EGG, respectively). All diets contained 20% total protein (wt:wt). All rats received their respective diets for 8 wk, at a stage of growth and development that translates to adolescence in humans, until 14 wk of age, a point at which ZDF rats exhibit overt T2D. Weight gain was measured 5 d/wk, and circulating 25-hydroxyvitamin D [25(OH)D] was measured by ELISA. Mean values were compared by 2-factor ANOVA. Results The 20% EGG diet maintained serum 25(OH)D at 30 nmol/L in ZDF rats, whereas the 10%, 5%, and 2.5% EGG diets did not prevent insufficiency, resulting in mean serum 25(OH)D concentrations of 24 nmol/L in ZDF rats. Body weight gain was reduced by 29% (P < 0.001) and 31% (P < 0.001) in ZDF rats consuming 20% and 10% EGG diets, respectively, and by 16% (P = 0.004) and 12% (P = 0.030) in ZDF rats consuming 5% and 2.5% EGG diets, respectively, compared with CAS. Conclusions Whole-egg–based diets exerted a dose-dependent response with respect to attenuating weight gain. These data could support dietary recommendations aimed at body weight management in individuals predisposed to obesity and T2D.

Dexamethasone can modulate the synthesis and organization of cytokeratins in cultured differentiating rat hepatocytes

1985 ◽  
Vol 63 (6) ◽  
pp. 448-457 ◽  
Author(s):  
Normand Marceau ◽  
Helene Baribault ◽  
Isabelle Leroux-Nicollet
Keyword(s):  
Rat Hepatocytes ◽  
Relative Mass ◽  
Close Relationship ◽  
Lower Cell Density ◽  
Epidermal Growth ◽  
High Production ◽  
Normal Differentiation ◽  
Dose Dependent Increase ◽  
Dose Dependent ◽  
Hepatocyte Growth

Dexamethasone, added to suckling rat hepatocytes cultured in serum-free medium supplemented with insulin and epidermal growth factor (EGF), caused a selective dose-dependent increase in cytokeratin synthesis. The response was dependent on the initial hepatocyte density. At 5 × 104 hepatocytes/cm2 a concentration of 1 or 10 μM dexamethasone, in the presence of insulin, enhanced the synthesis of a 55 000 relative mass (Mr) cytokeratin and to a lesser degree a 49 000 Mr cytokeratin, whereas at 1 × 105 hepatocytes/cm2 10 μM dexamethasone preferentially stimulated a 51 000 Mr component. Preferential synthesis of the 51 000 Mr component also occurred when either 1 or 10 μM dexamethasone was added to cultures seeded at 2 × 105 hepatocytes/cm2. The inclusion of EGF along with dexamethasone and insulin in cultures at 2 × 105 cells/cm2 yielded a differential effect of dexamethasone concentration equivalent to that observed at the lower cell density in absence of EGF. Under conditions where increased cytokeratin synthesis was observed, the hepatocytes maintained a high production of albumin and lost their capacity to produce α-fetoprotein, a change in gene expression associated with the normal differentiation of suckling rat hepatocytes. In contrast, no enhancement of cytokeratin synthesis was observed in hepatocytes following addition of EGF and insulin only, a condition that promoted hepatocyte growth and the maintenance of α-fetoprotein production. The dexamethasone-induced enhancement of cytokeratin synthesis was still present at 3 days postseeding. At this time, morphological observations by phase-contrast and immunofluorescence microscopy using monoclonal antibodies against the 55 000 and 49 000 Mr components revealed that under growth-promoting conditions the hepatocytes were spread and the cytokeratin filaments were stretched, whereas under differentiation-promoting conditions the cultures constitute a compact monolayer of cells exhibiting highly ordered filaments. These data suggest a close relationship between synthesis and organization of cytokeratins and promotion of differentiation of suckling rat hepatocytes by glucocorticoids.

scholarly journals Pharmacokinetics and Pharmacodynamic Effects of an Oral Ghrelin Agonist in Healthy Subjects

2007 ◽  
Vol 92 (5) ◽  
pp. 1814-1820 ◽  
Author(s):  
Franziska Piccoli ◽  
Lukas Degen ◽  
Carol MacLean ◽  
Shajan Peter ◽  
Luisa Baselgia ◽  
...  
Keyword(s):  
Body Weight ◽  
Oral Delivery ◽  
Oral Formulation ◽  
Growth Hormone Secretagogue ◽  
Drug Concentrations ◽  
Dose Study ◽  
Oral Doses ◽  
Dose Dependent Increase ◽  
Dose Dependent ◽  
Male Subjects

Abstract Context: An oral formulation of EP01572, a peptidomimetic growth hormone secretagogue, was studied. An oral delivery system would be preferable in many of the possible therapeutic indications of ghrelin agonists such as EP01572. Objectives: Our objective was to establish the pharmacological profile and the GH-releasing activity of increasing oral doses of EP01572 in healthy volunteers. In addition, the pharmacokinetics and pharmacological effects of EP01572 were investigated after intraduodenal (ID) administration. Setting: This study was a single-center escalating dose study with oral and ID applications. Subjects and Methods: In the first part, EP01572 was given orally to 36 male subjects; the treatment consisted of one oral dose of either EP01572 or placebo (0.005, 0.05, and 0.5 mg/kg body weight). Six subjects received two additional oral doses of EP01572: 0.125 and 0.25 mg/kg body weight. In the second part, the following treatments were performed in a randomized order: 1) administration of a bolus of saline (placebo) to the small intestine; 2) ID administration of a bolus of EP01572 at 0.2 mg/kg body weight; 3) ID perfusion of a bolus of EP01572 at 0.35 mg/kg body weight; and 4) ID perfusion of a bolus of EP01572 at 0.5 mg/kg body weight. Results: The oral and ID administration of EP01572 induced a rapid and dose-dependent increase in plasma drug concentrations and a potent GH release in healthy male volunteers. Conclusions: This study showed that EP01572 was active with regard to stimulation of GH release in humans after oral and ID administration.

scholarly journals Neurotoxic effect in lactating mice pups received oseltamivir phosphate (tamiflu) through milk from dosed nursing mothers during lactation period

2012 ◽  
Vol 36 (1) ◽  
pp. 75-84
Author(s):  
Areej B. Abass
Keyword(s):  
Body Weight ◽  
Clinical Symptoms ◽  
Body Weight Gain ◽  
Control Group ◽  
Lactation Period ◽  
Dependent Manner ◽  
Neurotoxic Effect ◽  
Nursing Mothers ◽  
Oseltamivir Phosphate ◽  
Dose Dependent

The present study was aimed to evaluate neurotoxic effects of oseltamivir phosphate in lactating pups of orally dosed mice mothers during lactation. Twelve recently parturited female albino mice were divided equally into three groups, one control and two treated groups, each group consists of 4 dosed dams and 8 chosen pups .The nursing dams of T1 and T2 dosed daily orally with 1mg/kg and 5mg/kg,oseltamivir phosphate respectively representing the therapeutic dose and 5 fold dose of drug while control group dosed with distilled water. Lactating mice pups of all groups examined for the following parameters: First parameter was body weight changes and gain: In which T1group showed significant increase in mice pups body weight gain after 14 day of treatment in comparison with control group and T2. Second parameter was clinical symptoms observation /daily, all treatment groups that showed neurotoxic symptoms appeared from 1st dose and extended along the next few days of treatment to be gradually disappeared and completely lost within the last days of treatment in dose dependent manner.These neurotoxic symptoms were weakness, convulsions ,lay on back or side, extended body, incoordination ,extended limbs and limbs stiffness. Third parameter was gross and histopathological studies which demonstrate that the brain was the most affected organ beside extensive lesions in liver, kidney, stomach and small intestine of treated groups in dose dependent manner.In conclusion of this study revealed that Oseltamivir phosphate produce neurotoxic effect in mice pups through indirect administration by nursing mothers dosing during lactation period and the level of toxicity was in dose dependent manner.

Oncogenic Evaluation of 3,3′-Dimethoxybenzidine Dihydrochloride in BALB/c Mice

1990 ◽  
Vol 9 (1) ◽  
pp. 71-77 ◽  
Author(s):  
G. J. Schieferstein ◽  
W. G. Sheldon ◽  
R. R. Allen ◽  
D. L. Greenman ◽  
W. T. Allaben
Keyword(s):  
Drinking Water ◽  
Body Weight ◽  
Dose Level ◽  
Body Weight Gain ◽  
Inbred Mouse ◽  
Inbred Mouse Strain ◽  
Current Investigation ◽  
Related Effect ◽  
Male And Female ◽  
Males And Females

3,3′-Dimethoxybenzidine, a congener of the known carcinogen benzidine, is carcinogenic in the rat and possibly the hamster. This study was undertaken to assess carcinogenicity in an inbred mouse strain. Male and female (840 each) BALB/c mice were given 0, 20, 40, 80, 160, 315, or 630 ppm of 3,3′-dimethoxybenzidine dihydrochloride in their drinking water. At the serial sacrifices (13, 26, 39, 52, 78, or 112 weeks on dose), detailed necropsies and histopathologic examinations were performed. There was a decrease in water consumption at the 630 ppm dose level. Compared with controls, the 630 ppm dose produced a decrease in body weight gain of 10.7 and 13.3% in males and females, respectively, at 48 to 52 weeks on test. These weight decrements may be related to low water palatability at the 630 ppm dose level and may not reflect toxicity induced by 3,3′-dimethoxybenzidine itself. There was no treatment-related effect upon mortality or pathology. In summary, 3,3′-dimethoxybenzidine dihydrochloride was not carcinogenic in the mouse in the current investigation.

scholarly journals Genetic parameters for body weight and different definitions of residual feed intake in broiler chickens

2019 ◽  
Vol 51 (1) ◽  
Author(s):  
Wossenie Mebratie ◽  
Per Madsen ◽  
Rachel Hawken ◽  
Hélène Romé ◽  
Danye Marois ◽  
...  
Keyword(s):  
Body Weight ◽  
Feed Intake ◽  
Broiler Chickens ◽  
Genetic Parameters ◽  
Body Weight Gain ◽  
Genetic Correlations ◽  
Residual Feed Intake ◽  
Nutrient Utilization ◽  
Male And Female ◽  
Males And Females

Abstract Background The objectives of this study were to (1) simultaneously estimate genetic parameters for BW, feed intake (FI), and body weight gain (Gain) during a FI test in broiler chickens using multi-trait Bayesian analysis; (2) derive phenotypic and genetic residual feed intake (RFI) and estimate genetic parameters of the resulting traits; and (3) compute a Bayesian measure of direct and correlated superiority of a group selected on phenotypic or genetic residual feed intake. A total of 56,649 male and female broiler chickens were measured at one of two ages ($${\text{t}}$$ t or $${\text{t}} - 6$$ t - 6 days). BW, FI, and Gain of males and females at the two ages were considered as separate traits, resulting in a 12-trait model. Phenotypic RFI ($${\text{RFI}}_{\text{P}}$$ RFI P ) and genetic RFI ($${\text{RFI}}_{\text{G}}$$ RFI G ) were estimated from a conditional distribution of FI given BW and Gain using partial phenotypic and partial genetic regression coefficients, respectively. Results Posterior means of heritability for BW, FI and Gain were moderately high and estimates were significantly different between males and females at the same age for all traits. In addition, the genetic correlations between male and female traits at the same age were significantly different from 1, which suggests a sex-by-genotype interaction. Genetic correlations between $${\text{RFI}}_{\text{P}}$$ RFI P and $${\text{RFI}}_{\text{G }}$$ RFI G were significantly different from 1 at an older age but not at a younger age. Conclusions The results of the multivariate Bayesian analyses in this study showed that genetic evaluation for production and feed efficiency traits should take sex and age differences into account to increase accuracy of selection and genetic gain. Moreover, for communicating with stakeholders, it is easier to explain results from selection on $${\text{RFI}}_{\text{G}}$$ RFI G than selection on $${\text{RFI}}_{\text{P}}$$ RFI P , since $${\text{RFI}}_{\text{G}}$$ RFI G is genetically independent of production traits and it explains the efficiency of birds in nutrient utilization independently of energy requirements for production and maintenance.

Ontogenesis of epidermal growth factor in liver of BALB mice

1988 ◽  
Vol 255 (1) ◽  
pp. E28-E32
Author(s):  
N. P. Laborde ◽  
M. Grodin ◽  
G. Buenaflor ◽  
P. Brown ◽  
D. A. Fisher
Keyword(s):  
Body Weight ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Postnatal Life ◽  
Twofold Increase ◽  
Life After Death ◽  
Epidermal Growth ◽  
Males And Females ◽  
Liver Tissues

To characterize the ontogenesis of hepatic epidermal growth factor (EGF) metabolism in normal BALB mice, we measured serum and liver concentrations of EGF and liver concentrations of pre-pro EGF mRNA. Female and male animals were studied at 1, 2, 5, 7, and 10 wk of life. After death, body weight and length were measured, and serum and liver tissues were collected for EGF determinations. Immunoreactive serum EGF (means +/- SE) increased at 7 and 10 wk and was significantly higher (P less than 0.05) in males (465 +/- 58 and 683 +/- 120 pg/ml) than females (188 +/- 52 and 295 +/- 64 pg/ml). Liver EGF concentrations were low at 1, 2, and 5 wk, significantly increasing (P less than 0.01) at 10 wk to 179 +/- 36 vs. 268 +/- 49 pg/mg protein for females and males, respectively (female and male values were significantly different, P less than 0.01). Pre-pro EGF mRNA was examined at 1, 2, 3, 5, 7 and 10 wk. EGF message increased in liver to highest values at 10 wk in both males and females. There was a high correlation between serum and liver EGF concentrations during the first 10 wk (r = 0.97 and 0.85 for males and females, respectively) and a twofold increase in liver EGF mRNA between 3 and 10 wk of postnatal life. These results suggest that liver may be an important source of circulating EGF in developing BALB mice.

scholarly journals A Dose-Dependent Effect of Carnipure® Tartrate Supplementation on Endurance Capacity, Recovery, and Body Composition in an Exercise Rat Model

Nutrients ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1519
Author(s):  
Kazim Sahin ◽  
Cemal Orhan ◽  
Osman Kucuk ◽  
Nurhan Sahin ◽  
Mehmet Tuzcu ◽  
...  
Keyword(s):  
Body Weight ◽  
Antioxidant Capacity ◽  
Serum Glucose ◽  
Control Group ◽  
Time To Exhaustion ◽  
Endurance Capacity ◽  
Exercise Regimen ◽  
Male Wistar Rats ◽  
Dose Dependent Increase ◽  
Dose Dependent

The objective of this work is to investigate the effects of Carnipure® Tartrate (CT) supplementation with or without exercise on endurance capacity, recovery, and fatigue by assessing time to exhaustion as well as body weight and composition in rats. In addition, antioxidant capacity has been evaluated by measuring malondialdehyde (MDA) levels and antioxidant enzyme (superoxide dismutase, SOD; catalase, CAT; glutathioneperoxidase; GSHPx) activities. Fifty-six male Wistar rats were divided into eight groups including seven rats each. A control group did not receive CT nor exercise. Another control group received 200 mg/kg CT without exercise. The other six groups of rats went through an exercise regimen consisting of a 5-day training period with incremental exercise capacity, which was followed by 6 weeks of the run at 25 m/min for 45 min every day. CT was supplemented at 0, 25, 50, 100, 200, and 400 mg/kg per day during the 6 weeks. Rats submitted to exercise and supplemented with CT had a significant and dose-dependent increase in time to exhaustion and this effect seems to be independent of exercise (p < 0.05). Additionally, recovery and fatigue were improved, as shown by a significant and dose-dependent decrease in myoglobin and lactic acid plasma levels, which are two markers of muscle recovery. CT supplementation led to a dose-response decrease in body weight and visceral fat. These effects become significant at 200 and 400 mg/kg doses (p < 0.05). Additionally, the antioxidant capacity was improved, as shown by a significant and dose-dependent increase in SOD, CAT, and GSHPx. Serum MDA concentrations decreased in exercising rats with CT supplementation. CT supplementation led to a decrease in serum glucose, triglycerides, and total cholesterol concentrations with the lowest levels observed at 400 mg/kg dose (p < 0.05). These effects correlated with a significant dose-dependent increase in serum total L-carnitine, free L-carnitine, and acetyl-carnitine, which linked the observed efficacy to CT supplementation. These results demonstrate that CT supplementation during exercise provides benefits on exercise performance, recovery, and fatigue as well as improved the lipid profile and antioxidant capacity. The lowest dose leads to some of these effects seen in rats where 25 mg/kg corresponds to 250 mg/day as a human equivalent.

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