Response of adrenal 3β-hydroxy-Δ5-steroid dehydrogenase to adrenocorticotropin treatment in thiouracil-fed male mice

1982 ◽  
Vol 60 (1) ◽  
pp. 83-87 ◽  
Author(s):  
Lee A. Meserve ◽  
Shu-Mei Ting

A number of parallels can be drawn between the reported endocrine status of thiouracil-fed young rodents and that of aged animals, particularly with regard to the hypothalamus–pituitary–adrenal axis. Since the activity of the adrenal steroidogenic enzyme 3β-hydroxy-Δ5-steroid dehydrogenase (3β-HSD) has been shown to be depressed in aged rats and mice, the present study was done to determine whether exposure of young mice to thiouracil had a similar effect on adrenal 3β-HSD activity. Feeding the goitrogen thiouracil at 0.25% (w/w) of the maternal diet from conception, and keeping it 0.25% of the offsprings diet after weaning, significantly elevated activity of 3β-HSD per gram of adrenal gland above control levels in 4-month-old mice, perhaps to compensate for depressed adrenal mass. Daily subcutaneous injections of physiological saline (0.9%) for 4 days was sufficient to increase 3β-HSD activity per gram of adrenal tissue in euthyroid (P < 0.05) but not in thiouracil-fed mice. Subcutaneous administration of ACTH (2 IU daily for 4 days) significantly increased adrenal 3β-HSD activity to comparable levels in thiouracil-fed and euthyroid animals. Thus, thiouracil enhances the activity of 3β-HSD per gram of adrenal tissue and does not prevent response of enzyme activity to exogenous ACTH.

2017 ◽  
Vol 1 (3) ◽  
pp. 117-127
Author(s):  
Yasaman Mansouri ◽  
Yasmin Amir ◽  
Michelle Min ◽  
Raveena Khanna ◽  
Ruiqi Huang ◽  
...  

Background: Adherence to subcutaneous biologic agents for the treatment of psoriasis can be negatively influenced by injection pain.Objective: To explore the differences in injection site pain when patients are pre-treated with heat or cold, versus no pre-treatment prior to administration of a subcutaneous biologic agent.Methods: In an observational cohort study, patients receiving subcutaneous injections of ustekinumab were randomly assigned to receive pretreatment with ice, heat, or no intervention over three visits. Post-dose, patients rated pain on a 100 mm visual analogue scale (VAS).Results: There was an increase in the VAS score for both heat (2.51, P=0.30) and ice (3.33, P=0.16), compared to no intervention. No differences were found between the two intervention groups (-0.83, P=0.73). On average, females had the same VAS scores with ice compared to that of no intervention (-0.12, P=0.97) and a non–significant decrease of 3.29 points (P=0.38) with heat. Males had increased pain scores by 5.65 points (P=0.07) with ice and by 6.39 points (P=0.04) with heat.Limitations: Pain is a subjective measurement and objective quantification is difficult.Conclusions: On average, neither heat nor cold application reliably reduced pain. Our results do not support the application of heat or cold prior to ustekinumab injection.


1933 ◽  
Vol 58 (5) ◽  
pp. 569-574 ◽  
Author(s):  
Herbert M. Evans ◽  
Edwin L. Gustus ◽  
Miriam E. Simpson

The gonadotropic hormone of the blood of the pregnant mare has been greatly concentrated by adsorption on active aluminum hydroxide followed by elution. The preparations so obtained gave demonstrable gonadotropic effects within 100 hours in 21 day old female mice following three subcutaneous injections of 0.001 mg. in 1 cc. of physiological saline. As is well known, other gonadotropic substances do not cause conspicuous development of the male gonads but injections of comparatively large doses of these preparations into immature male rats caused marked development of the testes, which in 10 days were trebled in weight. An astonishing increase in the weight of the seminal vesicles resulted, for these organs were approximately 75 times heavier than in controls.


2014 ◽  
Vol 66 (5) ◽  
pp. 1376-1382 ◽  
Author(s):  
C.M. Souza ◽  
P.A. Auler ◽  
D.C. Reis ◽  
G.E. Lavalle ◽  
E. Ferreira ◽  
...  

Ketoprofen, a nonsteroidal anti-inflammatory drug (NSAID) has proven to exert anti-inflammatory, anti-proliferative and anti-angiogenic activities in both neoplastic and non-neoplastic conditions. We investigated the effects of this compound on tumor development in Swiss mice previously inoculated with Ehrlich tumor cells. To carry out this study the solid tumor was obtained from cells of the ascites fluid of Ehrlich tumor re-suspended in physiological saline to give 2.5x106cells in 0.05mL. After tumor inoculation, the animals were separated into two groups (n = 10). The animals treated with ketoprofen 0.1µg/100µL/animal were injected intraperitoneally at intervals of 24h for 10 consecutive days. Animals from the control group received saline. At the end of the experiment the mice were killed and the tumor removed. We analyzed tumor growth, histomorphological and immunohistochemical characteristics for CDC47 (cellular proliferation marker) and for CD31 (blood vessel marker). Animals treated with the ketoprofen 0.1µg/100µL/animal showed lower tumor growth. The treatment did not significantly influence the size of the areas of cancer, inflammation, necrosis and hemorrhage. Moreover, lower rates of tumor cell proliferation were observed in animals treated with ketoprofen compared with the untreated control group. The participation of ketoprofen in controlling tumor malignant cell proliferation would open prospects for its use in clinical and antineoplasic therapy.


2011 ◽  
Vol 57 (5) ◽  
pp. 30-37
Author(s):  
I I Dedov ◽  
V A Peterkova ◽  
T Iu Shiriaeva ◽  
E V Nagaeva ◽  
N N Volevodz ◽  
...  

The objective of the present study was to evaluate the efficacy and safety of the application of the new soluble pharmaceutical form of Rastan for subcutaneous injections at a dose of 15 IU/ml and compare its action with that of Rastan lyophilisate, 4 IU, designed to prepare solutions for subcutaneous administration. The two dosage forms are used to treat children suffering from growth hormone deficiency. The study included patients at the age from 4 to 12 years presenting with idiopathic growth hormone deficiency; they were randomized into two groups. During the first three months, the patients of both groups were treated with different pharmaceutical forms of recombinant growth hormone (rGH). The children in group 1 were given Rastan for subcutaneous injections and those in group 2 received Rastan lyophilysate for the preparation of solutions for the subcutaneous administration. Either form of GH was used at an equal daily dose of 0.033 mg/kg b.w. The patients of both groups showed marked improvement of the parameters of linear growth within the first three months. The difference in the growth rates was not significantly different between the two groups which suggests the identical effect of the two forms of rGH. During the next 9 months when the patients of both groups were treated only with the rGH for subcutaneous injections, the absolute growth response, height SDS, and the level of insulin-like growth factor 1 (IGF-1) continued to increase. It points out to the stable growth-promoting effect of Rastan for subcutaneous injections. No clinically significant abnormal changes in the results of complete blood cell count and biochemical analysis of blood were apparent during 12 months of therapy with this form of rGH. The same was true of the levels of free T4, cortisol, and prolactin in the blood. No adverse effects attributable to the therapy with rGH were documented.


1972 ◽  
Vol 126 (1) ◽  
pp. 99-106 ◽  
Author(s):  
P. V. Maynard ◽  
E. H. D. Cameron

C19-steroid metabolism in homogenates of adrenal tissue from rats and mice has been studied. Production of these compounds from [7α-3H]cholesterol by rat adrenal tissue appeared to follow a route independent of pregnenolone. The major products of [7α-3H]-dehydroepiandrosterone metabolism by rat adrenal tissue were 5α-reduced steroids, principally androsterone, epiandrosterone and 5α-androstanedione. No differences in metabolism of [7α-3H]dehydroepiandrosterone or [4-14C]pregnenolone were detected between adrenal tissue from Sprague–Dawley, Wistar and Osborne–Mendel rats, but experiments with the Snell rat adrenocortical tumour 494 showed that this tissue had low 5α-reductase activity. In contrast, the major products of [7α-3H]dehydroepiandrosterone metabolism by mouse adrenal tissue were 5β-reduced steroids. Differences were observed between LACA and NH strains of mice in that there was a lower metabolism of androstenedione by NH mouse adrenal and a considerable difference in the proportions of aetiocholanolone and epiaetiocholanolone produced.


2016 ◽  
Vol 51 (3) ◽  
pp. 264-272 ◽  
Author(s):  
Sara Hestehave ◽  
Gordon Munro ◽  
Tina Brønnum Pedersen ◽  
Klas S P Abelson

Researchers performing experiments on animals should always strive towards the refinement of experiments, minimization of stress and provision of better animal welfare. An adequate analgesic strategy is important to improve post-operative recovery and welfare in laboratory rats and mice. In addition, it is desirable to provide post-operative analgesia using methods that are minimally invasive and stressful. This study investigated the antinociceptive effects of orally administered buprenorphine ingested in Nutella® in comparison with subcutaneous buprenorphine administration. By exposing the animal to a thermal stimulus using a hot plate, significant antinociceptive effects of voluntarily ingested buprenorphine administered in Nutella® were demonstrated. This was evident at doses of 1.0 mg/kg 60 and 120 min post administration ( P < 0.01), although antinociceptive effects were not as marked as with subcutaneous administration, and had a later onset. It is advised to administer the oral formulation of buprenorphine in Nutella® in a 10-fold higher dose, as well as approximately 60 min earlier, than with the more commonly employed subcutaneous route of administration.


1996 ◽  
Vol 30 (7-8) ◽  
pp. 729-732 ◽  
Author(s):  
Jan T Jørgensen ◽  
Janne Rømsing ◽  
Mette Rasmussen ◽  
Jørn Møller-Sonnergaard ◽  
Lisbeth Vang ◽  
...  

OBJECTIVE: To compare injection pain after subcutaneous administration of four different solution volumes. DESIGN: Double-blind, randomized, prospective, multiple crossover study. SETTING: Steno Diabetes Centre, Gentofte, Denmark. PARTICIPANTS: Eighteen healthy volunteers, 9 women and 9 men, aged 21-30 years. METHODS: The subjects were injected with four different volumes (0.2, 0.5, 1.0, 1.5 mL) of NaCl 0.9%. The study was performed on 2 days with a 1-week washout period between the study days. On each study day the subjects received four injections in each thigh. To evaluate the validity of our pain assessing model the subjects received eight injections of 0.5 mL on one of the study days. Pain assessment was done immediately after each injection using both a 10-cm visual analog scale (VAS) and a six-item verbal rating scale (VRS). RESULTS: A significant difference in pain score on both the VAS (p < 0.05) and the VRS (p < 0.01) was seen between the four injection volumes. The pain was significantly increased with volumes of 1.0 and 1.5 mL. No significant difference in injection pain could be detected between 0.2 and 0.5 mL and between 1.0 and 1.5 mL. No significant period or carryover effect could be detected in the study. A significant correlation between the pain score on the VAS and the pain score on the VRS was found (r = 0.79, p < 0.0001). CONCLUSIONS: The pain of a subcutaneous injection is related to injection volume in the thigh. The results show that increasing the volume from 0.5 to 1.0 mL increases the pain significantly. The findings from this study should be considered when injection preparations for subcutaneous administration are formulated. The volume should generally be less than 1.0 mL if injected into the thigh.


2020 ◽  
Vol 187 (11) ◽  
pp. e98-e98
Author(s):  
Kimberley Stee ◽  
Bart J G Broeckx ◽  
Mike Targett ◽  
Sergio A Gomes ◽  
Mark Lowrie

BackgroundThe administration of cytosine arabinoside (CA) by continuous rate infusion (CRI) at the time of diagnosis has been shown to improve the 3-month survival of dogs diagnosed with meningoencephalomyelitis of unknown origin (MUO), compared to subcutaneous administration. The benefit of administering subsequent sequential CA subcutaneous injections is unknown. This study compares the outcomes of a CA CRI protocol with (CRI+subcutaneous group) or without (CRI group) follow-up CA subcutaneous injections; both groups received adjunctive prednisolone.MethodsForty-two dogs diagnosed with MUO were recruited (CRI group) and compared with 41 historical control dogs (CRI+subcutaneous group) in a prospective, controlled clinical trial with 36 months of follow-up.ResultsSuccess rates were respectively 64.3 per cent and 65 per cent in the CRI and the CRI+subcutaneous groups at 40 weeks following diagnosis, and 32.5 per cent and 35.9 per cent at 36 months following diagnosis. The median time to relapse was 299 and 285 days for the CRI and the CRI+subcutaneous groups, respectively. No statistically significant difference was found (P≥0.05).ConclusionNo clear benefit was identified in the administration of subsequent sequential CA subcutaneous injections after the first administration of CA by CRI for the treatment of dogs diagnosed with MUO.


1978 ◽  
Vol 88 (2) ◽  
pp. 347-353 ◽  
Author(s):  
Jorge D. Jacobi ◽  
Andres Carballeira ◽  
Lawrence M. Fishman

ABSTRACT Cortisol, corticosterone, epinephrine and norepinephrine have been identified for the first time in two adrenal cysts removed from patients without endocrine dysfunction. Total concentrations of corticosteroids and catecholamines in both capsule and fluid of these cysts were higher than in plasma of normal subjects but lower than in human adrenal tissue. The cysts contained preformed cholesterol in concentrations similar to normal adrenal parenchyma. Contrary to adrenal tissue, however, homogenates of cyst components failed to utilize [4-14C] cholesterol for steroid formation. The data presented suggest that hormones in adrenal cysts probably arise by passive diffusion from the surrounding gland and that the endocrine status of patients bearing adrenal cysts is determined by the adjacent non-cystic tissue.


1995 ◽  
Vol 4 (5) ◽  
pp. 331-338 ◽  
Author(s):  
M. Minnicozzi ◽  
W. N. Durán ◽  
D. Kim ◽  
G. J. Gleich ◽  
J. Wagner ◽  
...  

Interleukin-5 (IL-5) is a cytokine that preferentially effects the development and function of eosinophils, and is considered important in the pathophysiology of allergic inflammation. In this study, we evaluated the ability of recombinant human IL-5 (rHu IL-5) to promote tissue eosinophilia and the importance of this eosinophilia to pathological alterations in vascular function. Repetitive subcutaneous administration for 18 days of rHu IL-5 resulted in a 7-fold increase in the number of eosinophils found in the ipsilateral hamster cheek pouch membrane. The contralateral cheek pouch membrane and peritoneum of these animals showed lesser but significant elevations in the number of eosinophils. In contrast, denatured rHu IL-5 did not elevate eosinophils in these tissues. Through the use of intravital microscopy and fluorometric analysis, rHu IL-5 treated hamster cheek pouch membranes were evaluated for alterations in microvascular permeability, using plasma clearance of FITC-dextran 150 as an index. Despite promoting a prominent tissue eosinophilia, the repetitive subcutaneous injections of rHu IL-5 did not alter the clearance of FITC-dextran 150. Topical application of rHu IL-5 to the cheek pouch, also, had no effect on the clearance of FITC-dextran 150. Immunofluorescence observations using an antibody to the granule protein, eosinophil peroxidase, indicated that the recruited cells had not degranulated. Our results support the importance of IL-5 in the recruitment of tissue eosinophils, but further stimulation is probably required to cause degranulation of these cells and the ensuing tissue damage.


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