Effects of administering caffeine to pregnant rats either as a single daily dose or as divided doses four times a day

1987 ◽  
Vol 25 (2) ◽  
pp. 125-133 ◽  
Author(s):  
S.E. Smith ◽  
P.R. McElhatton ◽  
F.M. Sullivan
Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3622
Author(s):  
Jonathan Barra ◽  
Javier Cerda-Infante ◽  
Lisette Sandoval ◽  
Patricia Gajardo-Meneses ◽  
Jenny F. Henriquez ◽  
...  

Cancer therapy may be improved by the simultaneous interference of two or more oncogenic pathways contributing to tumor progression and aggressiveness, such as EGFR and p53. Tumor cells expressing gain-of-function (GOF) mutants of p53 (mutp53) are usually resistant to EGFR inhibitors and display invasive migration and AKT-mediated survival associated with enhanced EGFR recycling. D-Propranolol (D-Prop), the non-beta blocker enantiomer of propranolol, was previously shown to induce EGFR internalization through a PKA inhibitory pathway that blocks the recycling of the receptor. Here, we first show that D-Prop decreases the levels of EGFR at the surface of GOF mutp53 cells, relocating the receptor towards recycling endosomes, both in the absence of ligand and during stimulation with high concentrations of EGF or TGF-α. D-Prop also inactivates AKT signaling and reduces the invasive migration and viability of these mutp53 cells. Unexpectedly, mutp53 protein, which is stabilized by interaction with the chaperone HSP90 and mediates cell oncogenic addiction, becomes destabilized after D-Prop treatment. HSP90 phosphorylation by PKA and its interaction with mutp53 are decreased by D-Prop, releasing mutp53 towards proteasomal degradation. Furthermore, a single daily dose of D-Prop reproduces most of these effects in xenografts of aggressive gallbladder cancerous G-415 cells expressing GOF R282W mutp53, resulting in reduced tumor growth and extended mice survival. D-Prop then emerges as an old drug endowed with a novel therapeutic potential against EGFR- and mutp53-driven tumor traits that are common to a large variety of cancers.


2014 ◽  
Vol 44 (5) ◽  
pp. 378-388 ◽  
Author(s):  
Ana L. Amaral ◽  
Ederlan S. Ferreira ◽  
Valdir A. Neves ◽  
Aureluce Demonte

Purpose – This paper aims to determine the effects of 11S globulin isolated from Chickpea (Cicer arietinum L.) on lipid metabolism in animals subjected to a hypercholesterolemic and hyperlipidemic diet and compared to the drug simvastatin. Design/methodology/approach – Thirty-six male Wistar rats, kept in individual cages and under appropriate conditions, were separated into groups that were fed a normal diet (STD) containing casein as protein source and according to AIN-93G; a high-cholesterol diet (HC), normal diet plus 1 per cent cholesterol and 0.5 per cent cholic acid and 20 per cent coconut oil; HC diet plus the isolated 11S globulin (300 mg/kg/day); and HC diet plus the simvastatin (50 mg/kg/day), both dissolved in saline and administered by gavage for 28 days. After this time, the animals were killed. Findings – The results indicated that the addition of 1 per cent cholesterol and 0.5 per cent cholic acid induced hypercholesterolemia in the animals without interfering with their weight gain. Analyses of total cholesterol (TC), HDL-cholesterol (HDL-C) and triglycerides (TG) in the plasma, and TC and TG in the liver were made. The results show that the protein isolated from chickpea, and given as a single daily dose, did not affect the levels of plasma TC and its fractions, although decreasing the TG levels. Unlike the simvastatin, the chickpea protein significantly reduced TC and TG in the liver relative to HC group. Originality/value – A single daily dose of 11S globulin from chickpea contributed as only as additional 2.8 per cent of dietary protein intake. These findings demonstrate that 11S chickpea protein acts as a functional agent in the lipid metabolism in addition to its nutritional properties.


1977 ◽  
Vol 24 (1) ◽  
pp. 117-119 ◽  
Author(s):  
R. N. Pal ◽  
S. S. Negi

SUMMARYRuminal ammonia and blood urea levels were compared in fistulated steers eating paddy straw to appetite and given urea alone, urea plus oxalate, and complexes of urea with either formaldehyde (UFC) or oxalate (UOC), introduced into the rumen in a single daily dose. The solubilities of UFC and UOC in rumen liquor were 23·7 and 4·6% respectively of that of urea. Higher levels of ruminal ammonia and blood urea were recorded on urea than on other supplements.


1979 ◽  
Vol 57 (s5) ◽  
pp. 387s-389s ◽  
Author(s):  
J. S. Floras ◽  
P. Fox ◽  
M. O. Hassan ◽  
J. V. Jones ◽  
P. Sleight ◽  
...  

1. Twenty-four hour intra-arterial blood pressure measurements and electrocardiograms were obtained from 12 subjects with untreated essential hypertension. 2. The patients kept records of their activity, paying particular attention to times of retiring to bed, and times of waking in the morning. 3. All subjects were treated with a single daily dose of atenolol (50 to 200 mg) for between 2 and 9 months, and then underwent a second 24 h blood pressure study. 4. Arterial blood pressure was lowered significantly throughout the 24 h period with a single daily dose of atenolol.


1992 ◽  
Vol 72 (6) ◽  
pp. 2134-2139 ◽  
Author(s):  
R. L. Hesslink ◽  
M. M. D'Alesandro ◽  
D. W. Armstrong ◽  
H. L. Reed

Thyroxine (T4) is required in species possessing brown adipose tissue (BAT) for the maintenance of cold tolerance and adaptation. In humans, who possess negligible quantities of BAT, the importance of T4 has not been demonstrated. We studied the effects of decreased serum T4 and thyrotropin (TSH) on human cold habituation after repeated cold air exposures. Eight men (T3+) received a single daily dose of triiodothyronine (T3; 30 micrograms/day), and another eight men (T3-) received a placebo. All 16 normal thyroid men underwent a standardized cold air test (SCAT) under basal conditions in January and again in March after eighty 30-min 4.4 degrees C air exposures (10/wk). Measurements of basal metabolic rate (BMR), O2 consumption (VO2), mean arterial pressure (MAP), plasma norepinephrine (NE), serum TSH, free and total T4, and free and total T3 were repeated before and after 8 wk of exposure. TSH, free T4, and total T4 were 50% lower for T3+ than for T3- subjects. Total and free T3 were not different between groups. BMR was unchanged after habituation, whereas the cold-stimulated VO2, MAP, and NE were significantly reduced for all subjects in March. The relationship between VO2 and NE (r2 = 0.44, P less than 0.001) during the initial SCAT was unchanged with habituation. We suggest that human cold habituation is independent of major changes in circulating T4 and TSH.


1988 ◽  
Vol 119 (1) ◽  
pp. 139-144 ◽  
Author(s):  
Yasuo Mashio ◽  
Mutsuo Beniko ◽  
Akemi Ikota ◽  
Hiroaki Mizumoto ◽  
Haruhiko Kunita

Abstract. A prospective randomized trial with the conventional divided doses (10 mg 3 times daily, N = 29) and a small single daily dose (15 mg once daily, N = 25) of methimazole for the treatment of Graves' hyperthyroidism was performed. Within 8 weeks, almost 80% of the patients in both groups became euthyroid. The mean time required to achieve the euthyroid state was 6.0 ± 2.8 and 6.0 ± 3.8 weeks, respectively. TSH binding inhibitor immunoglobulin was found in about 90% of the patients in both groups before methimazole treatment. However, a gradual fall of its levels was observed in nearly all patients after treatment. There was no difference in the mean levels of TSH binding inhibitor immunoglobulin between the two groups during therapy. We conclude that the single daily dose regimen of 15 mg of methimazole will control Graves' hyperthyroidism in most patients, and TSH binding inhibitor immunoglobulin levels decrease in this regimen in the same way as with the conventional divided dose regimen (10 mg 3 times daily).


1995 ◽  
Vol 20 (5) ◽  
pp. 1164-1168 ◽  
Author(s):  
C. Cabellos ◽  
P. F. Viladrich ◽  
R. Verdaguer ◽  
R. Pallares ◽  
J. Linares ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document