scholarly journals Sparse dose-dependent difference in skeletal effects of short-term glucocorticoid excess in outbred Swiss mice

2021 ◽  
pp. 100114
Author(s):  
Mikkel Bo ◽  
Annemarie Brüel ◽  
Jesper Skovhus Thomsen
Keyword(s):  
Short Term ◽  
Swiss Mice ◽  
Skeletal Effects ◽  
Dose Dependent

The calcium antagonist diltiazem inhibits calcification enhanced by calcitonin in growth cartilage of rats in ethane-1-hydroxy-1,1-diphosphonate (EHDP)-induced rickets

1986 ◽  
Vol 113 (1) ◽  
pp. 73-81 ◽  
Author(s):  
Masao Eguchi ◽  
Kenichiro Shibata ◽  
Fumio Wada ◽  
Hideya Kawamura ◽  
Takashi Shimauchi ◽  
...  
Keyword(s):  
Calcium Antagonist ◽  
Calcium Ion ◽  
Concomitant Administration ◽  
Proximal Region ◽  
Dependent Manner ◽  
Short Term ◽  
X Ray ◽  
Growth Cartilage ◽  
Term Administration ◽  
Dose Dependent

Abstract. In an animal model of human rickets developed by giving a short-term administration of large doses of EHDP to young rats, concomitant administration of [Asu1,7]eel calcitonin (CT) with EHDP resulted in the promotion of calcification in growth cartilage. In an attempt to clarify the mechanisms related to the accelerated calcification due to CT, the effects of diltiazem, a calcium antagonist, were studied. Diltiazem suppressed, in a dose-dependent manner, the accelerated calcification due to CT in the growth cartilage, as determined by findings on the soft X-ray photos, contact microradiograph and light microscopic histology of the proximal region of the tibia. This suppression was only evident when diltiazem and CT were given concomitantly. If it is assumed that diltiazem inhibits the entry of calcium ion into the cells of growth cartilage, in the same manner as seen in case of smooth muscle and myocardial cells, then our results indicate that intracellular concentrations of calcium might play an important role in the occurrence of accelerated calcification due to CT.

scholarly journals The Dose-dependent Dual Effects of Corticosterone on Spatial Memory Ability After Traumatic Brain Injury Are Mediated by Two Corticosteroid Receptor Systems

2021 ◽  
Author(s):  
Bin Zhang ◽  
Mengshi Yang ◽  
Qiongyu Yan ◽  
Xiaojian Xu ◽  
Fei Niu ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Spatial Memory ◽  
Signaling Pathways ◽  
Hippocampal Neurons ◽  
High Dose ◽  
Short Term ◽  
Memory Ability ◽  
Neurotoxic Effects ◽  
Dose Dependent

Abstract Background: Our recent studies reported the opposite effects of mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) on neuron survival after traumatic brain injury (TBI). However, as a mixed agonist for MR and GR, whether short term use of high-dose endogenous glucocorticoids exerts neurotoxic effects by excessive activation of GR, what is the set-point, and the possible signaling pathways remain unclear. This study examined the dose-dependent dual effects of corticosterone (CORT) on the spatial memory, the survival of hippocampal neurons and the possible receptor-mediated downstream signaling pathways after TBI.Methods: Based on controlled cortical impact (CCI) and CORT treatments, Sprague-Dawley rats (n=168) were randomly divided into the sham, CCI, CCI + CORT1 (0.3 mg/kg), CCI + CORT2 (3 mg/kg), CCI + CORT3 (30 mg/kg), CCI + CORT1 + spirolactone (spirolactone: 50 mg/kg/d), and CCI + CORT3 + RU486 (RU486: 50 mg/kg/d) groups. Brain tissues were collected on postinjury day 3 and processed for histology and western blot analysis.Results: On postinjury day 3, we tested the learning and memory ability, neuronal apoptosis in the hippocampus, activation levels of MR and GR, Bcl-2 family proteins, and apoptosis-related intracellular signaling pathways. We found that different doses of CORT exhibited dual effects on the survival of hippocampal neurons and the spatial memory. Lower doses of CORT (0.3, 3 mg/kg) significantly increased the activation of MR, upregulated the phosphorylation of Akt/CREB/Bad and the Bcl-2 expression, reduced the number of apoptotic neurons, and subsequently improved the spatial memory. In contrast, higher dose of CORT (30 mg/kg) exerted opposite effect by over activating GR, upregulating the expressions of P53/Bax, and inhibiting the Erk/CREB activities. Conclusion: The results suggest that there is a threshold between the neuroprotective and neurotoxic effects of endogenous GC, higher dose of which, even for short-term use, should also be avoided after TBI.

Short-term daily exercise activity enhances endothelial NO synthesis in skeletal muscle arterioles of rats

1994 ◽  
Vol 76 (5) ◽  
pp. 2241-2247 ◽  
Author(s):  
D. Sun ◽  
A. Huang ◽  
A. Koller ◽  
G. Kaley
Keyword(s):  
Nitric Oxide ◽  
Skeletal Muscle ◽  
Gracilis Muscle ◽  
Myogenic Tone ◽  
Control Group ◽  
Free Solution ◽  
Short Term ◽  
Daily Exercise ◽  
Exercise Activity ◽  
Dose Dependent

We aimed to test the hypothesis that as a consequence of short-term daily bouts of exercise the control of arteriolar smooth muscle by endothelium is altered. Rats ran on a treadmill once a day, 5 days/wk, for 2–4 wk (with gradually increasing intensity, up to 26 min at 22 m/min at a 1% grade by the beginning of the 3rd wk and up to 38 min at 28 m/min at a 2% grade by the beginning of the 4th wk) while a control group remained sedentary (SED). Cannulated and pressurized arterioles of rat gracilis muscle developed spontaneous myogenic tone, which was slightly enhanced in exercised (EX) compared with SED rat arterioles. At 80 mmHg pressure, the passive (Ca(2+)-free solution) and active diameters of SED and EX rat arterioles were 105.4 +/- 3.8 and 55.1 +/- 2.3 microns and 107.1 +/- 3.4 and 50.2 +/- 2.2 microns, respectively. Dose-dependent dilations to sodium nitroprusside (10(-8)-10(-6) M) and constrictions to norepinephrine (10(-8)-10(-6) M) were not affected in EX arterioles, whereas dilations to adenosine (10(-6)-10(-4) M) were significantly reduced. In contrast, dose-dependent dilations to acetylcholine (ACh; 5 x 10(-9)-10(-7) M) and L-arginine [precursor of nitric oxide (NO); 10(-4)-10(-3) M] were significantly enhanced (by 33–78 and 57–75%, respectively) in arterioles of EX compared with those of SED rats. Responses of arterioles to sodium nitrite were not different in SED and EX groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Reassessment of primed constant-infusion tracer method to measure urea kinetics

1987 ◽  
Vol 252 (4) ◽  
pp. E557-E564 ◽  
Author(s):  
F. Jahoor ◽  
R. R. Wolfe
Keyword(s):  
Steady State ◽  
Constant Infusion ◽  
Dependent Manner ◽  
Tracer Technique ◽  
Tracer Method ◽  
Priming Dose ◽  
Short Term ◽  
Urea Production ◽  
Urea Kinetics ◽  
Dose Dependent

The validity of the primed constant-infusion tracer technique to make short-term measurements of urea production rates (Ra) in humans in a physiological steady state and during disruption of steady state was evaluated. Four subjects received a primed constant infusion (P/I = 560 min) of [13C]urea for 8 h. A plateau in urea enrichment was reached after 2 h and maintained throughout. When [13C]- and [18O]urea were simultaneously infused into four subjects at P/I ratios of 560:1 and 360:1, respectively, both tracers reached plateau enrichment at the same time (2-4 h). The enrichment at plateau was a function of the infusion rate rather than the priming dose, and calculated urea Ra was the same with either prime. In five additional experiments the technique responded acutely to a physiological perturbation (alanine infusion) in a dose-dependent manner. The results confirm that this technique is appropriate for short-term measurements of urea Ra, and the requirement for accuracy in estimating the priming dose is not impractically stringent.

THE SYNTHESIS OF DNA AND RNA IN HUMAN CARCINOMATOUS ENDOMETRIUM IN SHORT-TERM INCUBATION IN VITRO AND ITS RESPONSE TO OESTRADIOL AND PROGESTERONE

1970 ◽  
Vol 48 (1) ◽  
pp. 29-38 ◽  
Author(s):  
S. NORDQVIST
Keyword(s):  
Nucleic Acids ◽  
Dna Synthesis ◽  
High Concentration ◽  
Short Term ◽  
Younger Women ◽  
Dna And Rna ◽  
Poorly Differentiated ◽  
Endometrial Carcinomas ◽  
Dose Dependent

SUMMARY Twenty-five endometrial carcinomas and three non-endometrial carcinomas were studied for the influence of various steroid hormones on the synthesis of DNA and RNA in short-term incubations in vitro. Endometrial carcinomas showed a dose-dependent sensitivity to progesterone in vitro, the response in both nucleic acids sometimes exceeding that of normal endometria. The mean reduction in DNA synthesis was to 46% and in RNA synthesis to 39% of the control values. Poorly differentiated carcinomas showed higher values of DNA synthesis than highly differentiated ones, as did carcinomas from younger women compared with those from older women. The response in vitro to progesterone was not correlated with these factors. Pregnenolone and a synthetic progestogen were less effective in vitro than progesterone. Oestradiol at a high concentration (20 μg/ml) in some cases significantly reduced the synthesis of both nucleic acids, possibly because of a specific 'toxic' action on the cells. No hormonal effects were observed in non-endometrial carcinomas.

scholarly journals Biological Safety and Biodistribution of Chitosan Nanoparticles

Nanomaterials ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 810 ◽  
Author(s):  
Dmitry Sonin ◽  
Evgeniia Pochkaeva ◽  
Sergei Zhuravskii ◽  
Viktor Postnov ◽  
Dmitry Korolev ◽  
...  
Keyword(s):  
Intravenous Administration ◽  
Dose Range ◽  
Chitosan Nanoparticles ◽  
Hemodynamic Changes ◽  
Short Term ◽  
Good Tolerance ◽  
Dose Dependent ◽  
Cultured Cardiomyocytes ◽  
Single Intravenous Administration ◽  
Observation Period

The effect of unmodified chitosan nanoparticles with a size of ~100 nm and a weakly positive charge on blood coagulation, metabolic activity of cultured cardiomyocytes, general toxicity, biodistribution, and reactive changes in rat organs in response to their single intravenous administration at doses of 1, 2, and 4 mg/kg was studied. Chitosan nanoparticles (CNPs) have a small cytotoxic effect and have a weak antiplatelet and anticoagulant effect. Intravenous administration of CNPs does not cause significant hemodynamic changes, and 30 min after the CNPs administration, they mainly accumulate in the liver and lungs, without causing hemolysis and leukocytosis. The toxicity of chitosan nanoparticles was manifested in a dose-dependent short-term delay in weight gain with subsequent recovery, while in the 2-week observation period no signs of pain and distress were observed in rats. Granulomas found in the lungs and liver indicate slow biodegradation of chitosan nanoparticles. In general, the obtained results indicate a good tolerance of intravenous administration of an unmodified chitosan suspension in the studied dose range.

Sign in / Sign up

Export Citation Format

Share Document