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Inhibitory effect of cortisone acetate on the stimulation of rat liver cytosol L-serrine. Pyruvate aminotransferase by dibutyryl adenosine 3,5-monophosphate.

An injection of cortisone acetate at a dose of 5 mg/100 g body weight concomitant with dibutyryl cyclic AMP prevents the increase in the activity of rat liver cytosol serine aminotransferase (L-serine:pyruvate aminotransferase, EC 2.6.1.51) elicited by the nucleotide with a lag of about 2 h. If the glucocorticoid is given 2 h prior to the nucleotide inducer, the lag disappears. The inhibitory effect of cortisone acetate gradually decays and is no longer detectable 12 h following its administration. Theophylline, insulin and glucose at doses which affect significantly the level of tyrosine aminotransferase, have not effect on the level of serine aminotransferase and on the cortisone inhibition. The inhibitory effect of the glucocorticoid on the dibutyryl cyclic AMP-mediated increase in serin aminotransferase diminishes with the age of animall. Increases in the enzyme activity by a single dose of glucagon can also be inhibited by cortisone acetate and actinomycin D as in the case with dibutyryl cyclic AMP as an inducer. The possibility of the existence of a specific inhibitory factor which is formed in response to cortisone acetate is discussed.

Age Factors↗

Effects of cortisone on mechanical activity and membrane ionic currents in frog auricular fibres.

The influence of cortisone on the mechanical and electrical activity of frog auricular fibres was investigated under voltage clamp conditions. 1. Cortisone exerted in vitro an inotropic action depending on concentration; a maximal positive inotropic effect was observed with 2 x 10(-4) g/ml of cortisone. 2. The positive inotropic effect of cortisone might be either an indirect sympathomimetic effect or an adrenaline-like effect. 3. The positive inotropic action of cortisone was correlated with modifications of the cardiac action potential: the amplitude of the action potential was enhanced while the resting membrane potential was unchanged; the amplitude and duration of the plateau were increased and the duration of the action potential was lengthened. 4. The electrical changes were related to an increase in the slow calcium current intensity resulting from an increase in the slow calcium conductance.

Animals↗

Role of plasma lipoproteins in cortisone-induced fat embolism.

The clinical syndrome of fat embolism can be a complication in patients who have suffered long-bone fracture, and has been associated with a number of conditions in which bone fracture is not a factor. The origin of embolic fat (bone marrow or depot fat versus plasma lipoproteins) has been debated. To test the hypothesis that alterations in the composition of plasma very-low-density lipoproteins (VLDL) could lead to their coalescence and subsequent impaction in pulmonary vasculature, New Zealand white rabbits were injected intramuscularly with 25 mg of cortisone twice a day for 2, 4, 6, 11 and 12 days. Blood samples were obtained from unanesthetized animals prior to the cortisone treatment and at sacrifice. Pulmonary fat embolism that was similar histologically to that found in the human patient with the clinical syndrome was produced in all rabbits treated for 4-12 days. After the fourth day, all animals were hyperlipidemic. There was a tenfold increase in plasma VLDL concentration and the mean particle diameter of the VLDL was increased from 620 A to 1016 A. The proportion of triglyceride (TG) was increased, protein (PR) and phospholipid (PL) were decreased and total cholesterol (TC) was unaltered (untreated controls: PR, 16.4%; TG, 58.5%; PL, 19.2%; TC, 6.7% and cortisone-treated: PR, 8.4%; TG, 75.1%; PL, 11%; TC, 6.4%). The lipid composition of pulmonary embolic fat from rabbits treated with cortisone for 6 or 11 days was TG, 81%; PL, 13% and TC, 6%. VLDL from similarly treated rabbits had a lipid composition of TG, 79%; PL, 14.5% and TC, 6.6%. The TC concentration of bone marrow and depot fat from animals treated with cortisone for 11 days was <1%, and the PL concentration was <2%. These data support the hypothesis that plasma lipoproteins, primarily the VLDL, when altered in size and composition can coalesce into globules of sufficient size to occlude peripheral capillaries.

Adipose Tissue↗

Comparative effects of a protein deprived diet on the weight, lymphocyte content and the number of DNA-synthesizing and dividing cells in the lymphoid organs of the rat. Influence of the diet on the stimulating action of phytohemagglutinin and the inhibitory action of cortisone.

The changes induced in adult male rats by a protein deprived (PD) diet lasting 7 weeks were investigated from the viewpoint of the cell contents of the popliteal lymph nodes (PLN), spleen and thymus; the levels of DNA-synthesizing lymphocytes counted on cell smear autoradiographs, and the levels of mitoses. The stimulating effect of a subplantar injection of phytohemagglutinin (PHA) and the inhibitory action of cortisone (3 mg/100 g per day for 5 days) were also determined in normal and PD rats. The PD diet significantly reduced the cell contents, primarily in the thymus, as well as the number of labeled cells and mitoses per mg of tissue and per entire organ. When expressed on the basis of 10(3) cells, the levels of both cell groups were also reduced in the spleen but not in the PLN's where they were already very low with a balanced diet. In the thymus, the sharp drop in the mitotic index (M.I.) contrasted with unchanged levels of labeled cells and an important increase in the labeling density per cell. PHA increased the M.I. to a great extent in the PLN's and spleen in normal rats but not in PD rats. In contrast, the labeling index (p. 10(3) cells) in the spleen, as well as the number of labeled cells per mg and per organ, increased in PLN's and the spleen after PHA to a much greater extent with a PD diet than with a normal diet. These results suggest a premitotic block of the cell cycle after protein deprivation. Also, the mitotic index appears to be a more reliable test, than the labeling index, of the lymphostimulating action of PHA and of its inhibition following protein removal from the diet. The effects of cortisone in normal rats resembled to a large degree those of a protein-free diet. If the hormone was administered to PD rats, the residual lymphocytes of the atrophic thymus were still more cortisone-sensitive than those of normal rats. On the contrary, DNA synthesizing cells in the PLN's and spleen, and mitoses in the spleen resisted cortisone in PD rats, while they were partly destroyed by the hormone in the controls. This suggests that primarily the cortisone-resistant lymphocytes of these organs are capable of synthesizing DNA after prolonged protein deprivation. The results are in agreement with the hypothesis of an intervention of endogenous glucocorticoid hormones in the protein lack-induced lymphoid involution.

Animals↗

[Cortisone level and emotional support by key figures in patients with bronchial asthma].

In a subgroup of patients with bronchial asthma, irrational fears of cortisone medication can be observed beyond justified worries about side-effects. A cortisone image which involves overemphasizing the threatening aspects of cortisone, often underlies noncompliant illness behaviour. In the present study, cortisone image and subjectively experienced emotional support by a key figure was investigated in 62 patients, all of whom had participated in the Düsseldorf Asthma treatment and teaching programme (ATTP). The data show that patients having a supportive relationship with their key figures are less likely to experience threatening aspects of cortisone. The findings are discussed in light of psychoanalytic object relations theory.

Adaptation, Psychological↗

[Cortisone-related glaucoma].

The cortisonical treatment has been more and more used in the last years, with an anti-inflammatory purpose, in ocular and general affections. The most severe ocular complications due to the prolonged treatment are the cortisonic glaucomas and the cortisonic cataract, both determining serious alterations of the visual function. The paper present the case of a patient, female, who was diagnosed five years before with pemphigus vulgaris, for which she has followed a prolonged cortisonic treatment. The ophthalmological examination has revealed the association with an open angle glaucomas and with a cortical posterior cataract, both having as a possible cause the prolonged prednisonic treatment. In order to prevent the affection we have to impose both the good judgement in prescribing the cortisonic medication and the periodical control of intraocular pressure in prolonged corticotherapy.

Cortisone↗

Inhibition of cortisone action in mice by heparin.

A single dose of heparin applied in a depot-form (Freund's incomplete adjuvant or Ca-phosphate gel) inhibits the effects of intraperitoneally injected cortisone on the lymphoid organs (thymus and spleen), on the peritoneal and peripheral lymphoid cell count and serum gamma globulin level as well as on the liver glycogen deposition in mice. The same dose of heparin did not influence the action of hydrocortisone measured on the thymic and spleen involution and liver glycogen content. The route of cortisone administration seems to be critical, as heparin shows no or only minor effects when cortisone is applied subcutaneously; moreover, the action of cortisone per se is more marked by subcutaneous than by intraperitoneal administration. The results suggest the hypothesis that heparin inhibits cortisone-cortisol conversion and this inhibition is mediated by macrophages.

Animals↗

Intravitreal injection of crystalline cortisone as adjunctive treatment of proliferative diabetic retinopathy.

PURPOSE: To report the clinical outcome and complications of intravitreal injections of crystalline cortisone in patients undergoing pars plana vitrectomy for treatment of proliferative diabetic retinopathy. METHODS: The prospective, interventional case series study included 29 consecutive patients (29 eyes) who underwent pars plana vitrectomy for treatment of complicated proliferative diabetic retinopathy associated with central retinal traction detachment. All patients received an intravitreal injection of 15 to 20 mg of crystalline triamcinolone acetonide at the end of surgery, and were operated on by the same surgeon. Mean follow-up time was 1.4 +/- 1.1 months (median, 1 month; range, 0.30 to 4.9 months). RESULTS: At the end of the follow-up period, the retina was attached in 26 of the 29 patients (89.7%). In three of the 29 patients (10.3%), a retinal redetachment had occurred. None of the patients developed iris neovascularization, and the iris neovascularization, present preoperatively in 12 patients, slightly to markedly regressed in all 12 patients. Preoperative and postoperative intraocular pressure values (P =.72) and blood glucose measurements did not vary significantly. A pseudohypopyon consisting of cortisone crystals in the inferior anterior chamber angle was detected in one patient and resolved spontaneously within 4 days. CONCLUSIONS: The present clinical study suggests that intravitreal injection of crystalline cortisone with most of the vehicle removed seems to be well tolerated by eyes undergoing pars plana vitrectomy for treatment of complicated diabetic proliferative retinopathy. In view of the antiphlogistic and antiproliferative effect of cortisone, future randomized clinical trials may be indicated to investigate further the role of intravitreal injection of crystalline cortisone in the treatment of proliferative diabetic retinopathy.

Adult↗

Effects of cortisone with and without heparin on angiogenesis induced by prostaglandin E1 and by S180 cells, and on growth of murine transplantable tumours.

Cortisone acetate, locally applied in sustained-release pellets, is effective in inhibiting angiogenesis induced by prostaglandin E1 in the rabbit cornea. The inhibitory effect of cortisone is not increased by addition of heparin. Similar results were obtained with angiogenesis induced by S180 cells. The effects of cortisone with and without heparin were also studied on 5 transplantable murine tumours: 3 variants of B16 melanoma, Lewis lung carcinoma and fibrosarcoma M4. The effect of cortisone in slowing the growth rate of tumours was modestly potentiated by heparin, but no regression of the tumour mass occurred.

Alprostadil↗

Determination of M+4 stable isotope labeled cortisone and cortisol in human plasma by microElution solid-phase extraction and liquid chromatography/tandem mass spectrometry.

A sensitive microElution solid-phase extraction (SPE) liquid chromatography/tandem mass spectrometry (LC/MS/MS) method has been developed and validated for the determination of M+4 stable isotope labeled cortisone and cortisol in human plasma. In this method, M+4 cortisone and M+4 cortisol were extracted from 0.3 mL of human plasma samples using a Waters Oasis HLB 96-well microElution SPE plate using 70 microL methanol as the elution solvent, and chromatographed on a Waters Symmetry C18 column (4.6 x 50 mm, 3.5 microm). M+9 cortisone and M+9 cortisol were used as the internal standards. A PE Sciex API 4000 tandem mass spectrometer interfaced with the liquid chromatograph via a turboionspray source was used for mass analysis and detection. The selected reaction monitoring (SRM) of precursor --> product ion transitions were monitored at m/z 365.2 [M+H](+) --> 167.0 and at m/z 367.3 [M+H](+) --> 125.1 for M+4 cortisone and M+4 cortisol, respectively. The lower limit of quantitation was 0.1 ng mL(-1) and the linear calibration range was from 0.1 to 100 ng mL(-1) for both analytes. This method demonstrated to be very reproducible and reliable.

Blood Chemical Analysis↗

The effect of cortisone acetate on the metabolism of Hymenolepis microstoma (cestoda:cyclophyllidea).

Hymenolepis microstoma grown in mice, treated with 1.25 mg cortisone acetate every second day, are heavier and have a significantly higher glycogen content than those in control mice. The dry/wet weight ratio and protein content however are unaffected. It is suggested that the increase in glycogen reserve and weight in H. microstoma from cortisone-treated mice is due to an immunosuppressive effect and better nutritional environment rather than hormonal action. Inclusion of 0.1 mg of cortisone per 100 ml of culture medium produces no change in worm weight in vitro. Single worm infections result in 100% recovery, but 30 worm infections provoke a rejection process which can be suppressed partially by administration of cortisone acetate.

Animals↗

Experimental central nervous system phaeohyphomycosis following intranasal inoculation of Xylohypha bantiana in cortisone-treated mice.

Experimental central nervous system (CNS) phaeohyphomycosis was established in cortisone-treated mice following intranasal exposure to conidia of Xylohypha bantiana (Cladosporium bantianum, C. trichoides). X. bantiana was recovered from the lungs of 78% of intranasally inoculated normal mice sacrificed within the first 3 days of infection and from 15% at day 28. The fungus was not recovered from the brains of normal mice. In contrast, X. bantiana was recovered from only 33% of the lungs of cortisone-treated mice within the first 3 days of infection. However, the fungus was recovered from the brain of 11% of cortisone-treated mice sacrificed or dying over a 28 day period. Histologically and temporally the CNS disease in cortisone-treated, intranasally inoculated mice was consistent with hematogenous dissemination from a primary pulmonary focus.

Animals↗

5'-AMP hydrolysis by suspensions and homogenates of pancreatic islet cells from normal and cortisone-treated rats.

Suspensions of endocrine pancreas cells were prepared by shaking collagenase-isolated rat islets of Langerhans in calcium-free buffer. When incubated with 1.0 mM substrate at pH 7.4, the cells split Pi from 5'-AMP at a rate of 87 nmol/h per microgram DNA, and from beta-glycerophosphate at a rate of 25 nmol/h per microgram DNA. Km for 5'-AMP was about 54 microM. Adenosine or theophylline inhibited the 5'-AMP hydrolysis. Homogenization of the cells increased the activity toward 5'-AMP by 23% and that toward beta-glycerophosphate by 115%. Injecting rats with cortisone had no effect on the 5'-AMP hydrolysis by whole cells but significantly increased the activity in cell homogenates; the intracellular activity toward 5'-AMP was more than doubled by the cortisone treatment. Staining whole islet cells for 5'-AMP-splitting activity resulted in a demarcation of the cell periphery in control rats. Cells from cortisone-treated rats showed heavier deposits of reaction product, and their cell periphery did not stand out as clearly. It is suggested that 5'-nucleotidase is largely an ectoenzyme in normal rat islet cells. The cells also contain an as yet unidentified intracellular phosphatase that seems to be solely responsible for the increased hydrolysis of 5'-AMP in cortisone-treated rats.

Adenosine Monophosphate↗

Hormonal influences on seizure kindling: the effects of post-stimulation ACTH or cortisone injections.

Repeated application of brain stimulation can lead to a progressively augmenting electrical and behavioral response-- a phenomenon termed seizure kindling. In this experiment, stimulation was delivered once per day, and was followed by peripheral (intraperitoneal) administration of ACTH or cortisone. An intermediate or a high dose of either hormone (0.3 IU or 3.0 IU of ACTH/animal, 10 mg or 25 mg cortisone/animal) delayed the completion of kindling if administered shortly after each kindling stimulation. Lower doses (0.03 IU of ACTH or 2 mg of cortisone) had no significant effects. The high dose of ACTH or cortisone was no longer effective if administration was delayed more than 4 h after stimulation. Peripherally administered ACTH and cortisone can influence processes initiated by the brain stimulation which presumably underlie the augmentation of response to successive stimulations. This time-limited action is analogous to the effects of these hormones on memory consolidation.

Adrenocorticotropic Hormone↗

The effect of oral contraceptives on plasma-free and salivary cortisol and cortisone.

The effect of a low estrogen oral contraceptive (OC) on glucocorticoid levels in plasma and saliva as well as glucocorticoid binding was studied in 23 healthy women using 30 micrograms ethinyl estradiol (EE2) + 150 micrograms desogestrel (Marvelon) (II). Fifteen healthy females with normal menses served as controls (I). Blood and salivary samples were taken between 9.00 and 9.30 a.m. on the 18th day of menstrual or pill cycle. Assay accuracy had been optimised by applying extraction and chromatographic purification before radioimmunoassay (RIA) of cortisol and cortisone in both plasma and salivary samples. Free steroid assays were performed by applying the same procedure to equilibrium dialysates obtained after dialysing plasma against an equal volume of buffer, instead of measuring tracer distribution. Corticosteroid Binding Globulin (CBG) was measured by a commercial RIA. As expected, CBG as well as plasma total cortisol were elevated in the pill group. Interestingly both plasma free and salivary cortisol were higher than in controls (free cortisol I: 18.0 +/- 7.95 nmol/l; II: 32.3 +/- 9.03 nmol/l; salivary cortisol I: 9.2 +/- 3.88 nmol/l; II: 18.8 +/- 6.92 nmol/l. Salivary cortisol closely parallelled plasma free cortisol both within and between the groups, though at a much lower level (about 50%). Free cortisone was slightly lower in the pill group (I: 10.8 +/- 2.55 nmol/l; II 8.5 +/- 1.86 nmol/l) whereas salivary cortisone was 2.3 (I) and 4.4 (II) times higher than plasma free cortisone and tended to follow the plasma free and salivary cortisol pattern, both within and between the study groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

The effect of oral contraceptive use and pregnancy on the daily rhythm of cortisol and cortisone.

The effect of oral contraceptives and of pregnancy on the daily rhythm of cortisol, and its metabolite cortisone in plasma and saliva has been investigated. In both conditions the total plasma cortisol levels were raised to the same extent, the mean values in saliva in the oral contraceptive users being intermediate between those in pregnancy and in the controls, particularly in the morning. Salivary cortisone levels were more related to salivary cortisol than to total plasma cortisone which exhibited a rather flat daily rhythm. There was a shift in peak values for salivary cortisol and cortisone towards late morning: this may be due to a delay in the daily activation of the hypothalamic-pituitary-adrenal axis in these patients.

Adult↗

Therapy of spontaneously metastatic HSV-2 induced hamster tumours with cortisone acetate administered with or without heparin.

Subcutaneous injection of cortisone acetate administered with or without oral heparin retarded the growth of two HSV-2 induced hamster fibrosarcomas. Histological sections showed no obvious difference between the vasculature of treated and untreated tumours although there were fewer infiltrating lymphocytes in treated tumours. Treatment was, however, found to be ineffective against metastatic development following resection of primary tumours. Natural killer cell activity was found to be greatly reduced in animals receiving heparin and/or cortisone acetate treatment and this may influence the effectiveness of treatment on the metastatic process. We conclude that treatment of tumours with cortisone plus heparin is no different from the response to cortisone used alone.

Animals↗

Automated direct high-performance liquid chromatographic assay for estetrol, estriol, cortisone and cortisol in serum and amniotic fluid.

An automated direct assay for the simultaneous determination of unconjugated estetrol, estriol, cortisone and cortisol in serum and amniotic fluid, using high-performance liquid chromatography with electrochemical detection and ultraviolet detection, has been developed. The analysis time is ca. 1 h. This system offers good reproducibility with low coefficients of variation (estetrol, 2.3%; estriol, 2.3%; cortisone, 2.6%; cortisol, 1.9%). Detection limits are low enough for routine determinations (estetrol and estriol, 150 pg; cortisone and cortisol, 5 ng). Comparison of the values measured by the present method and by radioimmunoassay revealed significant correlations for estetrol (r = 0.787, p less than 0.01), estriol (r = 0.957, p less than 0.01), cortisone (r = 0.956, p less than 0.01) and cortisol (r = 0.865, p less than 0.01). This system proved to be valuable in monitoring feto-placental function.

Amniotic Fluid↗