Administration Of Cortisone Research Articles

Interrelation of cortisone and 1,25 dihydroxycholecalciferol on intestinal calcium and phosphate absorption.

The interrelation of glucocorticoids and 1,25 dihydroxycholecalciferol (1,25(OH)2D3) on intestinal calcium and phosphate absorption was investigated. The active and passive transport of calcium and phosphate was evaluated by the in situ intestinal loop technique. Administration of cortisone resulted in a decrease of the luminal fluid and an increase of the luminal calcium and phosphate concentration. Under active transport conditions, administration of cortisone resulted in a decrease of net calcium absorption through two mechanisms: (1) depressed vitamin D-dependent calcium absorption, (2) increased vitamin D-independent calcium backflux. The enhancement of bidirectional phosphate flux by cortisone was independent of 1,25(OH)2D3. An enhancement of water movement by cortisone resulted in an increase of luminal calcium and phosphate concentration which favors the passive diffusion of these ions. Enhanced calcium diffusion by cortisone compensates for the inhibitory effect of cortisone on vitamin D-dependent calcium transport. However, enhanced phosphate diffusion by cortisone is additive to the effect of 1,25(OH)2D3.

Bile salt sulfotransferase: alterations during maturation and non-inducibility during substrate ingestion.

Development of the capacity for hepatic biotransformation of potentially toxic, endogenous compounds such as lithocholate may be dependent on induction by substrate or hormonal modulation. Our aim was to observe the ontogeny of hepatic sulfotransferase (ST) activity, a presumed detoxification pathway, and to determine the effect of substrate ingestion and cortisone administration on ST activity. Pregnant rats were fed a standard chow diet containing lithocholate; the maternal diet was continued during the suckling and weaning phase of the pups. Liver cytosol and serum were obtained from dams and from pups at weekly intervals from fetal life through 4 weeks of age. In controls, there was a progressive increase in hepatic ST activity from 6.2 +/- 2.9 pmol/mg protein per min, (mean +/- SEM) in fetal liver, 18.1 +/- 3.9 at 1 week, an 33.6 +/- 7.2 at 2 weeks to a peak of 56.4 +/- 11.8 at 3 weeks of age. In female rats older than 4 weeks of age, ST activity in hepatic cytosol was threefold higher than in males. There was a decline to adult levels (9.2 +/- 2.4 in males and 39.4 +/- 4.3 in females) at 56 days of life. Cortisone acetate administration had no effect on enzyme activity in pups except those 3 weeks old or older in which there was a precocious decrease in enzyme activity to adult levels. The administration of lithocholate caused a dose-related postnatal alteration of intrahepatic bile ducts manifest as cholangitis with ductular proliferation; hepatocytes were spared.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood pressure responses to prolonged infusions of adrenaline and noradrenaline in conscious dogs.

Adrenaline was infused intravenously into conscious dogs to test whether chronically elevated plasma levels can produce arterial hypertension. Adrenaline infused at 12.5 micrograms/kg/hr from 4 days produced no change in mean arterial pressure (1.1 +/- 2.7 mmHg) despite raising plasma adrenaline concentrations from 49 +/- 20 pg/ml to 1420 +/- 279 pg/ml. Myocardial tissue levels of adrenaline averaged 435 ng/g, compared to 20 ng/g in vehicle infused dogs. Longer infusions of adrenaline (11 days) at doses from 1.25 micrograms/kg/hr to 12.5 micrograms/kg/hr were also without significant effect on arterial blood pressure. In contrast, infusion of noradrenaline at 6.25 micrograms/kg/hr for 11 days produced sustained elevation of mean arterial pressure (11.7 +/- 5.1 mmHg). Although adrenaline infusion alone did not alter arterial pressure, a small rise (5.6 +/- 1.6 mmHg) was measured when the dogs were also given cortisone (50 mg twice daily). These results are therefore not in accord with the hypothesis that increased plasma levels of adrenaline may cause hypertension by activation of pre-junctional beta-adrenoceptors. However simultaneous administration of adrenaline and cortisone did elevate blood pressure, indicating that increases in both adrenal cortical and medullary hormones may be required to produce hypertension.

Studies on Experimental Aspergillosis in Immunodeficient Mice

Mice with either chemically suppressed immune response or with specifically induced T cell or B cell immunodeficienty were challenged with Aspergillus fumigatus spores. Chemical immunosuppressants used were cortisone, cyclophosphamide or silica. T cell deficiency was produced by thymectomy and ALS administration, whereas, B cell deficiency was produced by administration of anti-mouse IgM antibodies in newborn mice. The susceptibility of such animals to A. fumigatus challenge was monitored by mortality pattern and by demonstration of dissemination of fungus in different organs. The administration of cortisone or silica made mice highly susceptible to A. fumigatus infection, whereas, cyclophosphamide initially lowered host's resistance but later had little effect. Mice with B cell deficiency also did not differ significantly from normal animals. Similarly passive transfer of specific antibodies to A. fumigatus did not enhance the protection of the host to experimental aspergillosis. However, the deficiency of T cells and macrophages either alone or in combination made the animals highly susceptible to experimental aspergillosis. The results provide evidence that T cells and macrophages play essential role in immunity to murine aspergillosis. Whereas, B cell deficiency or even passive transfer of specific antibodies to A. fumigatus does not alter much the host's susceptibility to experimental aspergillosis.

Commentary: Three Decades of Folic Acid Antagonists in Dermatology

A little longer than 30 years ago, Gubner et al¹made the serendipitous observation that the folic acid antagonist aminopterin had a beneficial effect in the treatment of psoriasis. In the early 1950s, the inhibitory effects of aminopterin on the inflammatory and proliferative responses of the connective tissue in mesenchymal disorders were being investigated.¹Similar effects were being found with the administration of cortisone, also a newly used drug. Animal and clinical experiments showed that aminopterin was producing a greater inhibitory effect on epithelial tissues, whereas the major effects of cortisone therapy were appearing in mesenchymal tissues.²This unexpected finding occurred while Gubner et al1 were looking for an anti-inflammatory effect of aminopterin therapy in patients with rheumatoid arthritis, one of whom also had severe psoriasis. The beneficial response in this one patient (patient 3) led to the investigation of the use of aminopterin therapy in other

Influence of cortisone on immunologic tolerance in vivo: Cortisone prolongs the duration of unresponsiveness but fails to affect its induction

The influence of cortisone administration on either the induction or the duration of immunologic tolerance was examined in vivo. Tolerance induced by isologous IgG coupled to fluorescein was chosen because the hapten-bearing cell can be directly visualized and the hapten-specific immune response to either a TD antigen or a TI 2 antigen can be tested. It was found that cortisone facilitates the maintenance of tolerance, but fails to affect its induction to either class of antigen. Fluorescein-IgG-bearing cells are cortisone resistant. They are seen for a longer period of time in animals treated with cortisone and tolerogen than in animals treated with tolerogen, and fluorescent cells are either T or B cells. We propose that cortisone facilitates the maintenance of tolerance by maintaining a receptor blockade in vivo. This finding might have clinical implications for the treatment of autoimmunity.

Gold thioglucose-induced hypothalamic damage, hyperphagia, and obesity: dependence on the adrenal gland.

Previous studies from our laboratory suggested that adrenal hormones may participate, directly or indirectly, in the hypothalamic mechanism involved in the regulation of food intake. In the present studies, the effect of adrenalectomy on the development of gold thioglucose (GTG)-induced hyperphagia and obesity in mice was investigated. As expected, damage to the ventromedial hypothalamus by GTG was followed by hyperphagia and obesity. Ablation of the adrenal glands after the administration of GTG prevented the onset and development of hyperphagia and obesity. The administration of cortisone completely restored the hyperphagia and weight gain of GTG-treated adrenalectomized mice. The administration of desoxycorticosterone not only failed to restore the hyperphagia and obesity in these mice but, rather, led to a suppression of food intake, weight loss, and death. It is concluded that 1) GTG-induced hypothalamic hyperphagia and obesity are dependent on adrenal glucocorticoids, and 2) the ability of adrenal glucocorticoids to restore hyperphagia and obesity in hypothalamic lesioned adrenalectomized mice indicates that adrenal glucocorticoids can act on compounds outside of the ventromedial hypothalamus involved in the control of food intake.

Hypercalcemia due to Primary Hyperparathyroidism or Malignant Disease

The cortisone suppression test and some biochemical tests were evaluated in 13 patients with hypercalcemia due to primary hyperparathyroidism (PHP) and in 10 with hypercalcemia due to a malignant disease. The biochemical tests revealed that serum chloride was significantly raised in patients with PHP compared to patients with malignant diseases, whereas no differences were observed with regard to the serum values of corrected calcium, serum phosphate, chloride/phosphate ratio, HCO3-. Although serum values of parathyroid hormone were higher in patients with PHP, a consider-able overlap was observed between values in the two patient groups. Corrected serum calcium values were significantly suppressed during cortisone administration in patients with malignant disease compared to patients wit PHP, whereas prednisolone had no suppressive effect. The positive predictive value of the test was 80.0% and the negative predictive value 66.7%. We conclude that there is still no entirely reliable method to distinguish between hypercalcemia due to PHP or malignant disease.

Alterations in intestinal function in response to thyroxine and cortisone administration in undernourished rats.

Imposition of undernutrition during the suckling period considerably enhanced the intestinal uptake of D-glucose and glycine compared to a control group. Brush border sucrase, and alkaline phosphatase activities were drastically reduced while lactase and leucine amino peptidase levels were significantly elevated at weaning in nutritionally deprived pups as compared to control animals. Cortisone administration to undernourished rats depressed the uptake of D-glucose but stimulated that of glycine. Thyroxine treatment to undernourished animals reduced the uptake of glucose but had no effect on glycine absorption. Brush border sucrase and alkaline phosphatase activities were stimulated in cortisone- or thyroxine-injected undernourished rats but lactase activity was depressed under these conditions. Leucine aminopeptidase activity remained unaffected in cortisone- or thyroxine-administered undernourished pups.

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.

Role of liver lysosomes in uptake and biliary excretion of manganese in mice

To determine the mechanism of managanese excretion from the liver into bile, managanese content in blood, bile, whole liver, and subcellular fractions of liver was measured following intraperitoneal injection of a single dose of manganese (49 mg Mn (OAc) 2 · 4H 2O/kg body wt) in mice. Manganese in blood was rapidly incorporated into liver and appeared in bile within hours. Most of the absorbed manganese in liver was recovered in the mitochondrial-lysosomal fraction. Purified nuclei contained only one-tenth of the manganese found in the crude nuclear fraction. Sucrose density gradient centrifugation revealed that lysosomes took up and released manganese more rapidly than mitochondria. Also, manganese content in the liver and bile decreased following pretreatment with trypan blue. These values returned to normal with simultaneous administration of cortisone. Manganese released in vitro from the mitochondrial-lysosomal fraction and manganese in bile were measured as manganese acetate by gel filtration. The results suggest that liver lysosomes play an important role in intrahepatic movement and affect biliary excretion of absorbed manganese.

Agonist-promoted high affinity state of the beta-adrenergic receptor in human neutrophils: modulation by corticosteroids.

beta-Adrenergic agonists form high affinity complexes with receptors, resulting in activation of the associated adenylate cyclase. To examine the formation of the high affinity state of the receptor, curves were constructed for the competition of the full beta-adrenergic agonist isoproterenol, partial agonists cobefrin and soterenol, and the antagonist propranolol for [3H]dihydroalprenolol binding to beta-adrenergic receptors on human neutrophil membranes. Curve modeling by computer yielded a two-state binding model for the agonists, with distinct dissociation constants for the high (KH) and low (KL) affinity states. The ratio of dissociation constants (KL/KH) was found to be well correlated (P less than 0.01) with the drug's intrinsic activity for stimulation of adenylate cyclase. Thus, the degree of coupling of receptor occupation with adenylate cyclase activation is correlated with the magnitude of KL/KH. Administration of cortisone to humans resulted in a substantial rise in the proportion of receptors in the high affinity state and in the KL/KH determined from isoproterenol competition curves, as well as a rise in adenylate cyclase activity. Furthermore, in vitro exposure of human neutrophils to hydrocortisone resulted in a similar rise in KL/KH determined from isoproterenol competition curves. Therefore, one mechanism by which cortisone modulates beta-adrenergic receptor function appears to be through facilitating the formation of the high affinity state of the receptor, resulting in greater coupling of receptor occupation with adenylate cyclase activation.

Effect of cortisone administration on host-parasite relationships in early experimental syphilis.

Effect of cortisone administration on host-parasite relationships in early experimental syphilis.

Steroid related complications of double-lumen prostheses with cortisone

Sixty double-lumen prostheses with methylprednisolone added in the outer lumen are reviewed with a minimum follow-up of 6 months. Capsular contracture around these prostheses has been very low (11.6%), but unfavorable side effects of cortisone were observed in 24 implants, ranging from mild skin thinning to severe atrophy with loss of the prosthesis. The treatment of the complications is discussed and the question is raised as to whether the administration of cortisone is of any benefit.

"Allergic breakthrough" after antigen sensitization: height of IgE synthesis is temporally related to diurnal variation in endogenous steroid production.

Mice of the SJL strain normally display the low IgE responder phenotype. In the course of extensive studies on IgE responses with this strain of mice, it because apparent that the magnitudes of IgE antibody synthesis by SJL mice varied after antigen sensitization either alone or in conjunction with exposure to optimal enhancing doses of whole body irradiation. Analysis of the basis for this variability revealed that SJL respond to antigen sensitization by displaying cyclical IgE response curves determined by the time of day the sensitization is carried out. Moreover, when these low responders are converted to the high responder phenotype by low dose irradiation, the time of irradiation determines the magnitude of the IgE response obtained, whereas the time of antigen challenge determines the potential for generating a good response. The diurnal curve of IgE responses in both unirradiated and irradiation-enhanced low responder mice appears to be determined by normal variations in levels of endogenous corticosteroids, as indicated by the correlation between the normal diurnal curve of endogenous steroid production with the cyclical pattern of IgE responses. This apparent effect of endogenous steroid production on IgE antibody synthesis is supported by experiments demonstrating that the normal IgE pattern in both unirradiated and irradiated mice can be perturbed by administration of cortisone at the proper time of day. These results indicate that IgE antibody synthesis displays unique sensitivity to fluctuations in plasma steroid levels and may have significant implications for the role of steroids in the pathogenesis and management of allergic diseases.

Late Recurrence of Corticosteroid-Responsive Nephrotic Syndrome of Childhood

CHILDREN with minimal-change nephrotic syndrome usually respond to corticosteroid therapy and eventually enter complete remission before reaching adulthood. Although this disease entity is relatively common in both children and adults, it is extremely rare to encounter adult nephrotic patients who had nephrotic syndrome during childhood. We describe here a patient who had typical minimal-change nephrotic syndrome as a child and, after a corticosteroidinduced complete remission lasting 19 years, had severe nephrotic syndrome as an adult. Report of a Case A 26-year-old woman was seen at The Milton S. Hershey Medical Center in March 1977 with edema. In 1953, at the age of 22 months, she had been hospitalized with edema and ascites. Laboratory values at that time had included proteinuria (4+); serum albumin, 1.6 g/dL; BUN, 9 mg/dL; and serum cholesterol, 952 mg/dL. Following the administration of cortisone, 25 mg four times a day for 11 days, she had become

Zur Cortisonbehandlung der arteriosklerotischen Chorioretinopathie - eine katamnestische Studie

Visual acuity was tested in 34 patients (64 eyes), age 73.6 years, following systemic cortisone administration. A significant improvement in vision was found (82.81% and 67.19%) after three as well as after an average of ten months. It is remarkable that some of the patients (17 eyes), who were treated with vessel-active substances, and in some cases also with the vitamins A and E, also showed improvement in visual acuity comparable with the group treated with cortison only. In the small group (six eyes) with moist macular degeneration a slight improvement was only recorded in one case. The probable effects of cortisone in the course of arteriosclerotic chorioretinopathy are explained with the aid of histological findings of other authors.

Phosphatidylcholine synthesis in the developing small intestine.

1. Phosphatidylcholine synthesis in the foetal, newborn and adult small intestine of rats was studied by determination of cytidine diphosphocholine-1,2-diacylglycerocholine phosphotransferase (cholinephosphotransferase) and acyl-CoA-1-acyl-sn-glycerol-3-phosphocholine acyltransferase (lysophosphatidylcholine acyltransferase) activities and the incorporation of [1-14C]oleic acid into phosphatidylcholine. 2. Cholinephosphotransferase activity was low in foetal jejunum and ileum, increased 3-4 fold in the ileum by 6 days of age and by 12 days in the jejunum. Jejunal activity remained constant throughout weaning; ileal activity gradually decreased to values 25% of that of the jejunum. 3. Lysophosphatidylcholine acyltransferase activity was high in foetal jejunum and ileum, decreased 70% immediately after birth in the jejunum and increased to adult values by 12 days of age. Ileal activity decreased by 20% after birth, but decreased more rapidly at weaning to 30% of the activity in jejunum. 4. Initial rates and steady-state incorporation of [1-14C]oleic acid into phosphatidylcholine by jejunal rings of 10 day-old rats exceeded that observed in jejunal rings from adult rats by 2-4-fold. 5. In the postnatal jejunum, neither cholinephosphotransferase and lysophosphatidylcholine acyltransferase activities nor oleic acid incorporation were stimulated by cortisone administration in vivo.

Effect of Adrenalectomy on Liver Lipid Content of Fasted Rats

The interrelationship between thyroid and adrenal hormones in the regulation of lipid accumulation of the liver during fasting was examined with the use of intact, sham operated and adrenalectomized (ADX) rats previously fed a high carbohydrate diet. Adrenalectomy depressed the lipid accumulation of the liver induced by fasting. This was restored by cortisone administration, but not by epinephrine injection. Lipid content of the liver during fasting tended to be decreased in rats made hyperthyroid by intraperitoneal injection of thyroxine compared to euthyroid-fasted rats. In rats made hypothyroid by oral administration of propylthiouracil, liver lipid content during fasting was significantly higher than that of euthyroid-fasted rats. These responses of liver lipid to thyroid activity were minimized in ADX rats. Cortisone tended to restore completely the liver response to thyroid activity. The maximal response of liver lipid to cortisone was obtained in hypothyroid-ADX rats. The injection of epinephrine alone did not cause any significant change in liver lipid content of ADX rats regardless of the thyroid status. These findings suggest that glucocorticoid must be present for thyroid function to exert its effect on the lipid accumulation of the liver induced by fasting.

Influences of pituitary-adrenal hormones on kindling

The kindling process represents a progressively augmenting electrical and behavioral response to brain stimulation, that has been proposed as a model for the development of epileptogenesis. The first experiment examined the effects of hypophysectomy on the kindling process. The effects of hypophysectomy were found to be dependent on the number of days between hypophysectomy and the beginning of kindling. The kindling rate was slowed, compared to intact controls, when hypophysectomy was performed less than 2 weeks prior to the first kindling stimulation. However, if more than 4 weeks and passed since hypophysectomy, the kindling rate was faster than that of intact controls. The second experiment tested the influence of systemic administration of cortisone (10 mg/animal), upon kindling of control and hypophysectomized animals. Cortisone was found to reverse the kindling deficit of hypophysectomized animals at less than 2 weeks and to slow kindling of intact controls, but to have no effect on hypophysectomized animals at more than 4 weeks (at this dose). These results are interpreted as indicating that pituitary-adrenal hormones have profound influences on the kindling process, but it is unclear whether the influence is upon brain excitability or more directly upon modification of synaptic function.