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Sample records for cortisone

  1. EXPERIENCES WITH CORTISONE GIVEN ORALLY

    Science.gov (United States)

    Engleman, Ephraim P.; Kunkel, Peter; Welsh, Joseph E.; Molyneaux, M. Glenn

    1951-01-01

    The advantages of the oral administration of cortisone, when compared with cortisone given intramuscularly, include the more rapid appearance of therapeutic effects, which is of importance in the therapy of acute disease, and the faster dissipation of effects when the hormone is discontinued, which is of value when dangerous reactions occur. Oral dose schedules depend upon the degree of urgency or chronicity of the treated disease. In acute diseases the therapeutic results, in general, were disappointing. Cortisone may be of greater value in the long-term maintenance treatment of certain chronic diseases. By long-term therapy the authors mean practically continuous treatment until either the disease goes into spontaneous remission or undesirable effects of the drug require cessation of treatment. Critical selection of patients and constant supervision of therapy are vital to the successful administration of cortisone. Even with these precautions, however, the therapeutic use of cortisone must be regarded as experimental until the passage of time permits better appraisal of harmful effects. PMID:14848714

  2. The Lipid Bilayer Provides a Site for Cortisone Crystallization at High Cortisone Concentrations.

    Science.gov (United States)

    Alsop, Richard J; Khondker, Adree; Hub, Jochen S; Rheinstädter, Maikel C

    2016-03-03

    Cortisone is an injected anti-inflammatory drug that can cause painful side effects known as "steroid flares" which are caused by cortisone crystallizing at the injection site. We used molecular dynamics simulations and X-ray diffraction to study the interaction of cortisone with model lipid membranes made of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) at drug concentrations from 0 mol% to 50 mol%. Cortisone was found to partition in the lipid bilayer and locate in the hydrophilic to hydrophobic interface of the membranes. Cortisone strongly affects the integrity of the membrane, as quantified by a decreased membrane thickness, increased area per lipid, and decreased lipid tail order parameters. At cortisone concentrations of more than 20 mol%, signals from crystallized cortisone were observed. These crystallites are embedded in the bilayers and orient with the membranes. While the cortisone molecules align parallel to the bilayers at low concentrations, they start to penetrate the hydrophobic core at higher concentrations. Trans-membrane crystallites start to nucleate when the membrane thickness has decreased such that cortisone molecules in the different leaflets can find partners from the opposite leaflet resulting in a non-zero density of cortisone molecules in the bilayer center. We suggest that the lipid bilayer provides a site for cortisone crystallization.

  3. The Lipid Bilayer Provides a Site for Cortisone Crystallization at High Cortisone Concentrations.

    OpenAIRE

    Alsop, Richard J.; Adree Khondker; Hub, Jochen S.; Rheinstädter, Maikel C.

    2016-01-01

    Cortisone is an injected anti-inflammatory drug that can cause painful side effects known as "steroid flares" which are caused by cortisone crystallizing at the injection site. We used molecular dynamics simulations and X-ray diffraction to study the interaction of cortisone with model lipid membranes made of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) at drug concentrations from 0 mol% to 50 mol%. Cortisone was found to partition in the lipid bilayer and locate in the hydrophilic...

  4. TOPICAL USE OF CORTISONE IN UROLOGY

    Science.gov (United States)

    Schulte, T. L.; Reynolds, Lloyd R.; Hammer, Howard J.

    1954-01-01

    Cortisone was instilled into the bladder in the treatment of interstitial cystitis and contracted bladder, trigonitis and urethritis in females, nonspecific urethritis in males, and inflammation of the wall of the bladder. In infectious cases the hormonal therapy was used after antibacterial measures had failed. Improvement occurred quickly in most cases soon after cortisone therapy was given. In a few cases of interstitial cystitis and contracted bladder the relief obtained was inadequate and it was necessary to carry out overdistention procedures under visualization. When that was done, however, it was noted that the condition of the bladder was improved as compared with the conditions usually observed in cases in which cortisone treatment is not given before the procedure. Results of tests of the blood during therapy indicated that the benefits of the treatment were not owing to systemic absorption of cortisone. PMID:13150216

  5. Hypertension and the Cortisol-Cortisone Shuttle

    National Research Council Canada - National Science Library

    Quinkler, Marcus; Stewart, Paul M

    2003-01-01

    11β-Hydroxysteroid dehydrogenase type 2 (11β-HSD2) plays a crucial role in converting hormonally active cortisol to inactive cortisone, thereby conferring specificity on the mineralocorticoid receptor...

  6. What You Can Expect with a Cortisone Shot

    Science.gov (United States)

    ... can expect By Mayo Clinic Staff During the cortisone shot Your doctor might ask you to change ... anesthetic to provide immediate pain relief. After the cortisone shot Some people have redness and a feeling ...

  7. CORTISONE IN TREATMENT OF BRONCHIAL ASTHMA

    Science.gov (United States)

    Harris, Marvin S.

    1951-01-01

    Twenty patients with intractable asthma were treated with cortisone on various dosage schedules. Results indicated that a rapid improvement in the asthmatic state may be expected in four to five days with high level dosage of the hormone—usually a total dose exceeding 200 mg. per day at the beginning. If treatment is discontinued after a week, relapse usually will occur within a period of eight days. If small doses are given two or three times weekly, following initial response, relapse may not occur for 20 or 30 days. The interspersed administration of ACTH during an attempt to discontinue cortisone apparently was of no value. It therefore appears that cortisone control of intractable asthma is dependent on large dosage until clinical improvement is obtained, then approximately 100 mg. two or three times a week for maintenance of a reasonable state of health. PMID:14848726

  8. [Forgotten episodes of the birth of cortisone].

    Science.gov (United States)

    Uchibayashi, M

    2001-01-01

    During World War II, a rumor reached the United States and the United Kingdom that the Germans were successfully using an adrenal hormone product to protect Luftwaffe pilots from the adverse effects of high altitudes. The product was said to be obtained from adrenal glands collected in a huge amount in Argentina and transported by U-boats to Germany. The U. S. and the U. K. exerted their war efforts by setting up urgent research projects to produce similar products. The war ended in 1945, however, before the goal was achieved. The German rumor turned out to be groundless. Cortisone acquired fame in 1949 as "a miracle drug" for the relief of rheumatic pain. Its therapeutic discovery was an outcome of the untenable assumption that rheumatoid arthritis patients must have suffered from adrenal insufficiency and hormone deficiency. The war efforts have led to successful syntheses of cortisone after the war, and its industrial production has reduced its cost drastically from $200.00 per gram in 1949 to $10.00 in 1951. To overcome the cumbersome synthetic routes for cortisone, natural product sources were sought as possible starting materials, but without much success. A microbiological transformation of steroidal compounds was developed in 1952 to introduce an oxygen function into the molecular position 11 by a microorganism found at a window of a laboratory. The fermentation process required progesterone which found its timely supply in Mexico. The cost of progesterone went down from $2.00 per gram to $0.15 and that of cortisone further from $10.00 to $3.50 in 1955. An ample supply of cortisone at an affordable price was admirably achieved by the combination of progesterone derived from diosgenin of the Mexican yam and a microbiological oxidation process developed by a chance discovery of suitable organisms. The former is attributed to R. E. Marker and the latter to D. H. Peterson.

  9. Photocatalytic decomposition of cortisone acetate in aqueous solution

    NARCIS (Netherlands)

    Sobral Romao, J.I.; Saad, M.H.; Mul, Guido; Baltrusaitis, Jonas

    2015-01-01

    The photocatalytic decomposition of cortisone 21-acetate (CA), a model compound for the commonly used steroid, cortisone, was studied. CA was photocatalytically decomposed in a slurry reactor with the initial rates between 0.11 and 0.46 mg L−1 min−1 at 10 mg L−1 concentration, using the following

  10. Photocatalytic decomposition of cortisone acetate in aqueous solution

    NARCIS (Netherlands)

    Sobral Romao, Joana; Hamdy, Mohamed S.; Mul, Guido; Baltrusaitis, Jonas

    2015-01-01

    The photocatalytic decomposition of cortisone 21-acetate (CA), a model compound for the commonly used steroid, cortisone, was studied. CA was photocatalytically decomposed in a slurry reactor with the initial rates between 0.11 and 0.46 mg L−1 min−1 at 10 mg L−1 concentration, using the following he

  11. Relationship between cortisone and muscle work in determining muscle size

    Science.gov (United States)

    Goldberg, A. L.; Goodman, H. M.

    1969-01-01

    1. Large doses of cortisone caused marked atrophy of the plantaris muscle and other pale muscles of hind limbs of hypophysectomized rats, but hormone treatment had little effect on the size of the red soleus muscle. 2. Denervation increased the sensitivity of the soleus and plantaris to the catabolic effects of cortisone. 3. Increased work induced by tenotomy of the synergistic gastrocnemius made the plantaris muscle less sensitive to cortisone-induced atrophy. 4. Since the catabolic effects of cortisone are more pronounced in the less active muscles, it is suggested that in mobilizing body protein for gluconeogenesis the hormone spares those muscles physiologically most active. 5. The rapidity with which muscles lose weight in response to cortisone indicates that the hormone must decrease protein half-lives as well as decrease protein synthesis. PMID:5765854

  12. The History of Cortisone Discovery and Development.

    Science.gov (United States)

    Burns, Christopher M

    2016-02-01

    Philip Hench, Edward Kendall, and Tadeus Reichstein received the Nobel Prize in medicine and physiology in 1950 for their "investigations of the hormones of the adrenal cortex." Hench and Kendall took compound E from the laboratory to the clinic to the Nobel Prize in a span of 2 years. This article examines the paths that led to the day when the first rheumatoid arthritis patient received cortisone, and from there to the 1950 Nobel Prize ceremony. The aftermath of this achievement is also discussed. Although there have been significant advances in corticosteroid preparations and use since 1950, the side effects remain daunting. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. THE TOPICAL AND SYSTEMIC USE OF CORTISONE IN DERMATOLOGY

    Science.gov (United States)

    Newman, Ben A.; Feldman, Fred F.

    1951-01-01

    Part I of this report deals with the topical use of cortisone in a variety of skin diseases. Fifteen patients with chronic discoid lupus erythematosus, four patients with necrobiosis lipoidica diabeticorum, four with psoriasis, one with lichen planus and one with granuloma annulare were treated with cortisone ointment. All the patients with chronic discoid lupus erythematosus had some degree of improvement. In two patients with chronic lupus erythematosus, complete clearing of the eruption occurred. In four patients with necrobiosis lipoidica diabeticorum remarkable involution resulted. Patients with psoriasis, lichen planus and granuloma annulare were not benefited. Part II deals with the systemic use of cortisone. Eight patients with severe serum sickness-like penicillin reaction responded dramatically to parenterally administered cortisone. In two cases of pemphigus vulgaris and one case of Sulzberger-Garbe disease, the disease was kept in remission with cortisone administered intramuscularly as well as orally. Partial improvement resulted in a case of localized myxedema associated with malignant exophthalmus. Two patients with exfoliative dermatitis due to therapy with heavy metals responded dramatically to cortisone. No beneficial effects were noted in patients with chronic urticaria and atopic dermatitis. The systemic use of ACTH and cortisone in dermatology at present should be confined to patients with known fatal or hopelessly incapacitating diseases and to patients with extreme hypersensitivity reactions which may be protracted or life-endangering, and which can be controlled or cured with a relatively small total dosage of the agents in a short time. PMID:14886729

  14. THE INFLUENCE OF CORTISONE ON EXPERIMENTAL VIRAL INFECTION

    Science.gov (United States)

    Kilbourne, Edwin D.

    1957-01-01

    The administration of cortisone to chicken embryos infected with influenza B virus results in (a) an initial inhibition of viral synthesis and (b) an eventual increase in the final yield of virus attained. Increased yields of virus are attained regardless of the number of viral particles in the infecting inoculum or the proportion of particles which are infective. Changes in the distribution ratios of allantoic fluid and intramembrane virus are effected by cortisone only as the secondary result of reduction in viral synthesis. The manifest effect of cortisone on influenza A virus increase is inhibitory unless inocula containing relatively high proportions of inactive viral particles are used. PMID:13481248

  15. Hip Pain: Dry Needling Versus Cortisone Injections.

    Science.gov (United States)

    2017-04-01

    Greater trochanteric pain syndrome (GTPS) is chronic, intermittent pain and tenderness on the outside of the hip. The medical community once thought that a swollen hip bursa was the source of such pain, which led to the use of corticosteroid injections to the bursa to help decrease swelling and pain. However, researchers now believe that injuries to the muscles and tendons around the hip are the actual cause of this pain, and that inflammation is often not involved. A study published in the April 2017 issue of JOSPT explores dry needling as an alternative to cortisone injections to reduce pain and improve function in patients with GTPS. J Orthop Sports Phys Ther 2017;47(4):240. doi:10.2519/jospt.2017.0504.

  16. Increased Cortisol and Cortisone Levels in Overweight Children.

    Science.gov (United States)

    Chu, Lanling; Shen, Kangwei; Liu, Ping; Ye, Kan; Wang, Yu; Li, Chen; Kang, Xuejun; Song, Yuan

    2017-02-09

    BACKGROUND It has been unclear whether relatively high cortisol and cortisone levels are related to overweight in childhood, parental body mass index (BMI), and family dietary habits. The aim of this study was to compare cortisol and cortisone levels in urine and saliva from overweight and normal children, as well as correlations between children's BMI, parental BMI and family dietary behavior questionnaire score (QS). MATERIAL AND METHODS We analyzed the data from 52 overweight children and 53 age- and sex-matched normal-weight children aged 4-5 years. The concentrations of salivary cortisol (SF), salivary cortisone (SE), urinary cortisol (UF) and urinary cortisone (UE) were measured using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The family dietary behavior QS was answered by the parent mainly responsible for the family diet. RESULTS Average cortisol and cortisone levels were significantly higher in overweight children. There was no significant difference in the ratio of cortisol to cortisone (Rcc) and the marker of 11b-hydroxysteroid dehydrogenase type 2 (11β-HSD2) activities. The results displayed correlations among cortisol, cortisone, and Rcc. Positive correlations were weak-to-moderate between BMI and SF, SE, UF, and UE. There were correlations between BMI and maternal BMI (mBMI), and BMI was significantly associated with QS. CONCLUSIONS Our results suggest that cortisol and cortisone levels are associated with overweight in children, but the 11β-HSD2 activities showed no significant differences. Unhealthy family diet was associated with higher BMI, UF, and UE, and families with maternal overweight or obesity had a higher prevalence of children's overweight or obesity.

  17. Effects of growth hormone replacement on cortisol metabolism in hypopituitary patients treated with cortisone acetate

    NARCIS (Netherlands)

    Beentjes, JAM; Kerstens, MN; Dullaart, RPF

    2001-01-01

    Growth hormone (GH) replacement may inhibit 11 beta -hydroxysteroid dehydrogenase type 1 (11 beta HSD1) activity, resulting in diminished conversion of cortisone to cortisol. Moreover, GH replacement may lower bioavailability of hydrocortisone tablets. Therefore, substitution therapy with cortisone

  18. Salivary Cortisone Reflects Cortisol Exposure Under Physiological Conditions and After Hydrocortisone.

    Science.gov (United States)

    Debono, Miguel; Harrison, Robert F; Whitaker, Martin J; Eckland, David; Arlt, Wiebke; Keevil, Brian G; Ross, Richard J

    2016-04-01

    In this study we tested the use of salivary cortisol and cortisone as alternatives to serum cortisol. Salivary cortisol is often undetectable and contaminated by hydrocortisone. Salivary cortisone strongly reflects serum cortisol.

  19. Salivary cortisol and cortisone responses to tetracosactrin (synacthen).

    Science.gov (United States)

    Cornes, Michael P; Ashby, Helen L; Khalid, Yasmeen; Buch, Harit N; Ford, Clare; Gama, Rousseau

    2015-09-01

    To establish cutoff values for salivary liquid chromatography tandem mass spectroscopy cortisol and cortisone in defining adequate adrenocortical function during a standard synacthen test. We compared salivary liquid chromatography tandem mass spectroscopy cortisol and cortisone responses to those of serum cortisol measured on the Roche E170 immunoassay analyser and the Abbott Architect i2000 before and 30 min and 60 min following 0.25 mg of intravenous synacthen. Correlations of salivary cortisol and cortisone were bimodal and linear, respectively. Based on these correlations, adequate salivary cortisol and cortisone responses to synacthen were extrapolated from a serum cortisol (Roche) cut-off of 550 nmol/L and defined as 15 nmol/L and 45 nmol/L, respectively. The Abbott method correlated well with the Roche but gave results that were about 20% lower than the Roche method. Measurement of salivary cortisol and cortisone responses offers an alternative to those of serum cortisol during a synacthen test in the investigation of adrenal hypofunction. © The Author(s) 2015.

  20. The Cortisol to Cortisone Ratio during Cardiac Catheterisation in Sows.

    Science.gov (United States)

    Skarlandtová, Hana; Bičíková, Marie; Neužil, Petr; Mlček, Mikuláš; Hrachovina, Vladimír; Svoboda, Tomáš; Medová, Eva; Kudlička, Jaroslav; Dohnalová, Alena; Havránek, Štěpán; Kazihnítková, Hana; Máčová, Ludmila; Vařejková, Eva; Kittnar, Otomar

    2015-01-01

    A possible effect of mini-invasive heart intervention on a response of hypothalamo-pituitary-adrenal stress axis and conversion of cortisone to cortisol were studied. We have analysed two stress markers levels (cortisol, cortisone) and cortisol/cortisone ratio in 25 sows using minimally invasive heart catheterisation as the stress factor. The values of studied parameters were assessed in four periods of the experiment: (1) the baseline level on the day before intervention, (2) after the introduction of anaesthesia, (3) after conducting tissue stimulation or ablation, and (4) after the end of the catheterisation. For statistical analyses we used the non-parametric Friedman test for four dependent samples (including all four stages of the operation) or three dependent samples (influence of operation only, baseline level was excluded). Statistically significant differences in both Friedman tests were found for cortisol and for cortisone. We have found the highest level of cortisol/cortisone ratio in unstressed conditions, then it decreased to the minimal level at the end of the intervention. We have concluded that cortisol levels are blunted by the influence of anaesthesia after its administration, and therefore decrease back to the baseline at the end of the operation.

  1. Prevention by Cortisone of Aspirin -Induced Gastric Ulceration in The Rat

    Directory of Open Access Journals (Sweden)

    B. Dejanguiri

    1968-01-01

    Full Text Available The effect of cortisone on the experimental gastric ulceration produced by intraperitoneal injection of aspirin in the rat is studied. Cortisone has significantly prevented the appearance of aspirin_ induced gastric ulceration. The possible mechanism of this effect of cortisone is discussed.  

  2. EXPERIENCE WITH CORTISONE AND ACTH IN A PRIVATE CLINIC

    Science.gov (United States)

    Krupp, Marcus A.; Saier, Milton; Keddie, Frances; Tanner, Ralph; Snell, A. M.

    1951-01-01

    Cortisone and ACTH are valuable agents for treating a large variety of diseases. In appropriate situations they may save life. It may be possible to prevent loss of vision in eye disease or permanent damage to important viscera in generalized disease. With ready access to these agents through the pharmacist, it is important to know that cortisone and ACTH can be used in office practice provided patients are selected carefully and followed frequently and closely. Strict observation of criteria for selection of patients limited the size of the series of patients reported upon, but by the same token the incidence of complications from therapy was exceptionally small. Every physician who elects to employ these potent hormones must become familiar with their physiological effects and with the various methods of exhibiting them. Some of these effects are noted in this paper, but the experiences reviewed here provide an incomplete picture of the wide application of cortisone and ACTH. PMID:14848715

  3. Urinary cortisol/cortisone ratios in hypertensive and normotensive cats.

    Science.gov (United States)

    Walker, David J; Elliott, Jonathan; Syme, Harriet M

    2009-06-01

    Hypertension is a common problem in older cats, particularly associated with chronic kidney disease (CKD). Reduced activity of 11beta-hydroxysteroid dehydrogenase type 2 predisposes to hypertension in human patients by allowing excessive stimulation of the mineralocorticoid receptor by cortisol. This study was designed to test the hypothesis that reduced conversion of cortisol to cortisone contributes to the development of systemic hypertension in some cats with CKD and idiopathic hypertension (iHT). The study included 60 client-owned cats: 21 clinically normal, 16 normotensive cats with CKD (NTCKD), 14 hypertensive cats with CKD (HTCKD) and nine iHTs. Urine cortisol and cortisone were extracted into dichloromethane and chloroform, respectively, prior to analysis by radioimmunoassay. Data are reported as median and range. The Kruskall-Wallis test was used to compare cortisol:cortisone ratios between groups with post-hoc testing using the Mann-Whitney U test. Wilcoxon signed-ranks test was used to compare results before and after treatment of hypertensive cats with amlodipine. The urinary cortisol:cortisone ratio was significantly higher in clinically normal cats (0.87; 0.46-1.39) when compared to NTCKD (0.60; 0.35-1.20; Pcortisone ratio was detected (P=0.327). Reduced urinary cortisol to cortisone conversion does not appear to be associated with systemic hypertension in cats. In fact, the cortisol to cortisone shuttle appears to be more effective in cats with CKD (hypertensive and normotensive) and iHT than clinically normal cats. The mechanism for this potentially adaptive response to kidney disease is not clear.

  4. Simultaneous quantitative analysis of salivary cortisol and cortisone in Korean adults using LC-MS/MS.

    Science.gov (United States)

    Lee, Sanghoo; Kwon, Soonho; Shin, Hye-Jin; Lim, Hwan-Sub; Singh, Ravinder J; Lee, Kyoung-Ryul; Kim, Young-Jin

    2010-07-01

    The levels of salivary cortisol and cortisone in Korean adults were measured for the first time using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The salivary cortisol and cortisone were separated within 10 min. The regression coefficients (r) of the calibration curves were greater than 0.999 for the two steroids. The limits of quantitation (LOQ) were 0.2 ng/ml for cortisol and 1 ng/ml for cortisone. The intra-day precisions of the assay were cortisone respectively, and the inter-day precisions were cortisone, respectively. The salivary cortisone concentrations were approximately 4-9 times higher than those of salivary cortisol during the daytime. Diurnal rhythms, during which the cortisol and cortisone concentrations were higher in the morning than in the afternoon, were also observed. The present assay may be useful for the diagnosis of several adrenal dysfunctions in clinical biochemistry.

  5. REACTIVATION OF NON-INFECTIVE VIRUS IN A CORTISONE-INJECTED HOST

    Science.gov (United States)

    Kilbourne, Edwin D.

    1955-01-01

    The administration of cortisone to chick embryos inoculated with large quantities of inactive influenza B virus results in a rate of viral increase greater than is concommittantly observed with inocula of comparable infectivity which are devoid of inactive particles. Thus, more than a mere negation of autointerference is effected. It is concluded that in the presence of cortisone reactivation has occurred of non-infective virus to a state in which it can participate in viral synthesis. Cortisone-induced viral reactivation is dependent upon a high partide/cell ratio and is thus analogous to the previously described phenomenon of "multiplicity reactivation." Cortisone does not influence either homologous or heterologous viral interference unless reactivation of the inactive interfering virus occurs. Virus reactivable with cortisone possesses both interfering and enzymatic properties. Reactivation of virus with cortisone cannot be effected in vitro but is mediated by the host cell. Two hypotheses concerning the action of cortisone are presented. PMID:14354111

  6. Surface plasmon resonance immunosensor for cortisol and cortisone determination.

    Science.gov (United States)

    Frasconi, Marco; Mazzarino, Monica; Botrè, Francesco; Mazzei, Franco

    2009-08-01

    In this paper, we present a surface-plasmon-resonance-based immunosensor for the real-time detection of cortisol and cortisone levels in urine and saliva samples. The method proposed here is simple, rapid, economic, sensitive, robust, and reproducible thanks also to the special features of the polycarboxylate-hydrogel-based coatings used for the antibody immobilization. The sensor surface displays a high level of stability during repeated regeneration and affinity reaction cycles. The immunosensor shows high specificity for cortisol and cortisone; furthermore, no significant interferences from other steroids with a similar chemical structure have been observed. The suitability of the hydrogel coating for the prevention of nonspecific binding is also investigated. A good correlation is noticed between the results obtained by the proposed method and the reference liquid chromatography/tandem mass spectrometry method for the analysis of cortisol and cortisone in urine and saliva samples. Standard curves for the detection of cortisol and cortisone in saliva and urine are characterized by a detection limit less than 10 microg l(-1), sufficiently sensitive for both clinical and forensic use.

  7. Salivary cortisone is a potential biomarker for serum free cortisol.

    Science.gov (United States)

    Perogamvros, I; Keevil, B G; Ray, D W; Trainer, P J

    2010-11-01

    Salivary cortisol measurement is used as a practical surrogate for serum free cortisol. However, parotid tissue harbors 11β-hydroxysteroid dehydrogenase (11β-HSD2) activity converting cortisol to cortisone. This study was designed to assess the impact of parotid 11β-HSD2 activity on the measurement of salivary cortisol. PATIENTS, DESIGN, AND OUTCOME MEASURES: Study participants with changes in circulating corticosteroid-binding globulin (CBG) (±oral contraceptive, functionally CBG null) and controls were studied during adrenal stimulation by ACTH and postoral and iv hydrocortisone administration. Simultaneous serum and saliva samples were collected for the measurement of total serum cortisol (SerF) by immunoassay, and unbound cortisol and cortisone in serum (FreeF and FreeE) and saliva (SalF and SalE) by liquid chromatography-tandem mass spectrometry. ACTH stimulation increased SerF, FreeF, SalF, SalE, but not FreeE in all individuals. SerF significantly decreased after stopping oral contraceptive administration, but FreeF, SalF and SalE remained unchanged. In the hydrocortisone administration study, individual FreeF and SalE curves were nearly identical and SalE closely reflected FreeF in all participants, irrespective of CBG changes. The highest correlation in all (n = 537) matched serum-saliva samples was between SalE and FreeF (r = 0.95, P cortisone. We have shown that salivary cortisone closely reflects free serum cortisol after adrenal stimulation and hydrocortisone administration and is unaffected by CBG changes. Salivary cortisone has potential as a useful surrogate for serum free cortisol in research and clinical assessment, and further research in states of chronic glucocorticoid excess is now needed.

  8. Kinetics of insulin disappearance from plasma in cortisone-treated normal subjects

    DEFF Research Database (Denmark)

    Ellemann, K; Thorsteinsson, B; Fugleberg, S

    1987-01-01

    The effect of glucocorticoid excess on insulin disappearance from plasma was examined in eight normal men during cortisone treatment (50 mg orally twice daily for 4 d) and in the absence of any medication (control) in random order. Constant infusion of insulin (1-5 mU/kg/min) was used to achieve...... infusions was significantly less in the cortisone study than in the control study, while the parameter estimates for the kinetics of insulin disappearance from plasma were unaffected by cortisone. Thus, insulin action and insulin kinetics in the steady state are dissociated in normal subjects rendered...... insulin resistant by short-term cortisone treatment....

  9. THE EFFECT OF CORTISONE ON THE SERUM LIPIDS AND ON THE DEVELOPMENT OF EXPERIMENTAL CHOLESTEROL ATHEROSCLEROSIS IN THE RABBIT

    Science.gov (United States)

    Gordon, Dina; Kobernick, Sidney D.; McMillan, Gardner C.; Duff, G. Lyman

    1954-01-01

    An experiment was performed to determine the effect of cortisone on the serum lipids and on the development of experimental cholesterol atherosclerosis in the rabbit. Litter mate rabbits of the same sex were employed; both sexes were represented in the experiment. The report is based upon four experimental groups comprising (1) 12 rabbits fed cholesterol and treated with cortisone vehicle; (2) 12 rabbits fed cholesterol and treated daily with cortisone; (3) 11 rabbits treated with cortisone; and (4) 7 rabbits that received cortisone vehicle. It was observed that: (1) There was less aortic atherosclerosis in the cholesterol-fed cortisone-treated rabbits as judged by both morphological and chemical means than in the rabbits fed cholesterol without cortisone treatment. (2) Cortisone depressed appreciably the hypercholesterolemia resulting from the feeding of cholesterol to rabbits. (3) Cortisone treatment caused a moderate hypercholesterolemia in normal rabbits. (4) Cortisone caused a moderate increase in serum lipid phosphorus equal to that produced by cholesterol feeding alone. (5) The combination of cholesterol feeding and cortisone did not result in a higher phospholipidemia than either one of these agents alone. (6) Cortisone caused a great increase in serum-neutral fat; it was not apparent whether cholesterol feeding affected the neutral fat lipemia due to cortisone treatment alone. (7) The total cholesterol to lipid phosphorus ratio was about normal in the rabbits that received cortisone only. It was doubled in the animals receiving both cholesterol and cortisone, and it was increased about four times in those that received only cholesterol. The significance of the alterations in the serum lipids induced by cortisone is discussed in relation to the inhibition of the development of aortic atherosclerosis that occurred in the cholesterol-fed rabbits treated with cortisone. PMID:13152282

  10. Cortisone-sensitive, innate resistance to Hymenolepis nana infection in congenitally athymic nude rats.

    Science.gov (United States)

    Ito, A; Kamiyama, T

    1987-06-01

    The innate resistance of the unnatural rat host to the mouse tapeworm Hymenolepis nana is cortisone sensitive but thymus independent. When congenitally athymic nude rats were orally given eggs, cysticercoids, or adult worms of H. nana, no lumenal adults were established except when they were treated with cortisone acetate during the expected lumenal development. The effect of cortisone to promote adult maturation in the rats was compared in nude and normal rats given eggs of H. nana. The fecundity of the worms (assessed by the fresh worm biomass and the number of infective eggs produced) was much higher in cortisone-treated nude rats than in cortisone-treated normal rats. When the nude rats reconstituted with thymocytes were given eggs and treated with cortisone, the fecundity of H. nana dropped to the same level as in cortisone-treated normal rats. It is strongly suggested that the unnatural rat host has thymus-independent cortisone sensitive resistance to an initial infection (which is the main component of the innate resistance and blocks the lumenal establishment of this parasite) and thymus-dependent resistance (which suppresses the established worms' fecundity and may be ascribed to acquired resistance to the ongoing infection).

  11. Effect of cortisone acetate on 19S and 7S haemolysin antibody

    Science.gov (United States)

    Elliott, E. V.; Sinclair, N. R. St C.

    1968-01-01

    A single subcutaneous injectio of cortisone acetate (400–500 mg/kg body weight) depressed the serum haemolysin response of adult Swiss mice to sheep erythrocytes when administered near the time of antigen injection. The greatest suppression of the early haemolysin response occurred when cortisone was injected 3–4 days prior to antigen, while the late antibody response (20–30 days after antigen injection) was markedly decreased when cortisone was given up to 4 days after antigen. Cortisone depressed both 19S and 7S haemolysin when given prior to antigen, but depressed only the 7S antibody when administered after antigen. An attempt was made to correlate the depression of the immune response with the decrease in lymphoid tissue following cortisone treatment and a striking correlation was observed between the number of circulating lymphocytes at the time of antigen injection and the 7 day titres of total and 19S antibody. PMID:5697012

  12. Analysis of cortisol, cortisone and dexamethasone in human serum using liquid chromatography tandem mass spectrometry and assessment of cortisol: cortisone ratios in patients with impaired kidney function.

    Science.gov (United States)

    Ray, Julie A; Kushnir, Mark M; Rockwood, Alan L; Meikle, A Wayne

    2011-06-11

    We developed a high sensitivity method for simultaneous measurement of cortisol, cortisone and dexamethasone. Using this method, we compared concentrations of cortisol, cortisone and their ratios in samples from intensive care unit (ICU) and non-ICU patients, and cortisol and dexamethasone concentrations in patients with Cushing's and suspected Cushing's syndrome. Two hundred microliters of human serum aliquots were extracted using solid phase extraction and analyzed using liquid chromatography-tandem mass spectrometry. Primary mass transitions monitored for cortisol, cortisone and dexamethasone were m/z 363/121, 361/163 and 393/373 respectively. The limits of quantification for cortisol and cortisone were 0.3 μg/l (0.8 nmol/l) and for dexamethasone it was 0.5 μg/l (1.2 nmol/l). Total imprecision was cortisone ratio of ICU patient samples was found to be 2 times higher than non-ICU samples. 54.2% of patients after 1mg dose of overnight dexamethasone could be categorized as consistent with Cushing's syndrome. The method has high sensitivity and specificity. High cortisol to cortisone ratios in samples from ICU patients suggest change in activity of 11β-hydroxysteroid dehydrogenase in modulation of systemically available cortisol. Simultaneous measurement of dexamethasone and cortisol can be used to differentially diagnose diseases causing increased concentrations of cortisol. Copyright © 2011 Elsevier B.V. All rights reserved.

  13. Intraindividual stability of cortisol and cortisone and the ratio of cortisol to cortisone in saliva, urine and hair.

    Science.gov (United States)

    Zhang, Quan; Chen, Zheng; Chen, Shenghuo; Xu, Youyun; Deng, Huihua

    2017-02-01

    Cortisol, cortisone and the ratio of cortisol to cortisone in saliva, urine and hair are acute, short-term and long-term biomarkers to reliably assess the activity of hypothalamic-pituitary-adrenal (HPA) axis and 11β-hydroxysteroid dehydrogenase (11β-HSD). One key issue is whether these biomarkers have intraindividual relative stability. Salivary, urinary and hair cortisol was proven to show considerable long-term intraindividual relative stability. However, currently unknown is whether cortisone and the ratio in saliva, urine and hair show intraindividual relative stability. The present study utilized a longitudinal design to validate long-term stability within two weeks of three biomarkers in saliva and urine, and long-term stability within twelve months of three hair biomarkers. Salivary, urinary and hair steroids were measured with high performance liquid chromatography tandem mass spectrometry. Three biomarkers in urine and hair showed moderate test-retest correlations with coefficient (r) ranging between 0.22 and 0.56 and good multiple-test consistencies with coefficient of intraclass correlation (ICC) ranging between 0.42 and 0.67. Three single-point salivary biomarkers showed weak to moderate test-retest correlations (r's between 0.01 and 0.38) and poor to fair multiple-test consistencies (ICC's between 0.29 and 0.53) within two weeks. Three single-day salivary biomarkers showed moderate test-retest correlations (r's between 0.23 and 0.53) and good multiple-test consistencies (ICC's between 0.56 and 0.66) within two weeks. Three biomarkers in urine and hair showed moderate long-term intraindividual relative stability. Three single-point salivary biomarkers showed weak to moderate short-term and long-term intraindividual relative stability, but three single-day salivary biomarkers showed moderate short-term and long-term intraindividual relative stability. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. THz spectra of cortisone and the related medicine

    Science.gov (United States)

    Ma, Shihua; Ge, Min; Liu, Guifeng; Song, Xiyu; Zhang, Peng; Wang, Wenfeng

    2009-07-01

    THz-TDS are used to study four kinds of drug: cortisone, hydrocortisone, prednisone and prednisolone. The THz spectra of them are obtained and analyzed from 0.2 - 1.6 THz. The experimental results shows the four samples have the different THz spectra. Cortisone has a peak at 1.5 THz and a broad absorption peak at 0.96 THz, while hydrocortisone has a weak absorption peak that lies at 1.27 THz. At the same time the prednisone has the stronger absorption peaks than the others, and its two peaks shows at 1.24 THz and 1.5 THz. Prednisolone has a weak broad peak at 1.43 THz. The results of the theoretical calculation were performed using Gaussian 03 software with Density Functional Theory at the basis set of 6-31+G (d, p). The theoretical vibrational frequencies are compared with the experimental results, and the deviations are discussed. The THz spectra of the medicine show THz technique may be help to distinguish some different chemical bond and functional group.

  15. Photocatalytic decomposition of cortisone acetate in aqueous solution.

    Science.gov (United States)

    Romão, Joana Sobral; Hamdy, Mohamed S; Mul, Guido; Baltrusaitis, Jonas

    2015-01-23

    The photocatalytic decomposition of cortisone 21-acetate (CA), a model compound for the commonly used steroid, cortisone, was studied. CA was photocatalytically decomposed in a slurry reactor with the initial rates between 0.11 and 0.46 mg L(-1)min(-1) at 10 mg L(-1) concentration, using the following heterogeneous photocatalysts in decreasing order of their catalytic activity: ZnO>Evonik TiO2 P25>Hombikat TiO2>WO3. Due to the lack of ZnO stability in aqueous solutions, TiO2 P25 was chosen for further experiments. The decomposition reaction was found to be pseudo-first order and the rate constant decreased as a function of increasing initial CA concentration. Changing the initial pH of the CA solution did not affect the reaction rate significantly. The decomposition reaction in the presence of the oxidizing sacrificial agent sodium persulfate showed an observed decomposition rate constant of 0.004 min(-1), lower than that obtained for TiO2 P25 (0.040 min(-1)). The highest photocatalytic degradation rate constant was obtained combining both TiO2 P25 and S2O8(2-) (0.071 min(-1)) showing a synergistic effect. No reactive intermediates were detected using LC-MS showing fast photocatalytic decomposition kinetics of CA. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Hair cortisol and cortisone are decreased by natural sunlight.

    Science.gov (United States)

    Wester, Vincent L; van der Wulp, Nils R P; Koper, Jan W; de Rijke, Yolanda B; van Rossum, Elisabeth F C

    2016-10-01

    Hair glucocorticoids (cortisol and cortisone) are increasingly used as measures of long-term integrated exposure to glucocorticoid hormones. Glucocorticoids gradually disappear from the hair shaft, which may result from exposure to ultraviolet (UV) radiation in natural sunlight. We aimed to study the influence of sun exposure on hair glucocorticoids. Scalp hair samples were obtained from nine volunteers (median age 33 [range 21-81], 7 females), and part of each hair sample was exposed to three experimental conditions: repeated exposure to natural sunlight for 40h (natural UV), exposure to a high amount of artificial UV radiation, and storage in the dark (control). Hair cortisol (HairF) and cortisone (HairE) were quantified by liquid chromatography-tandem mass spectrometry. When compared to control, HairF was decreased in 9 out of 9 hair samples after natural sunlight exposure (median decrease -3.1pg/mg or -54%, PUV radiation (-4.7pg/mg or -75%, P=0.003). HairE decreased in 8 out of 9 samples, both after natural sunlight (-7.6pg/mg or -32%, P=0.012) and artificial UV (-10.7pg/mg or -52%, P=0.026). Exposure to natural sunlight decreases the glucocorticoid content of scalp hair, apparently through UV radiation, and is therefore an important confounder that should be considered in studies involving the measurement of hair glucocorticoids. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Serum concentrations of cortisol and cortisone in healthy dogs and dogs with pituitary-dependent hyperadrenocorticism treated with trilostane.

    Science.gov (United States)

    Sieber-Ruckstuhl, N S; Boretti, F S; Wenger, M; Maser-Gluth, C; Reusch, C E

    2008-10-18

    The serum concentrations of cortisol and cortisone were measured in 19 healthy dogs and in 13 dogs with pituitary-dependent hyperadrenocorticism (PDH) before and one hour after an injection of synthetic adrenocorticotropic hormone (ACTH). In the dogs with pdh, the cortisol and cortisone concentrations were measured before and after one to two weeks and three to seven weeks of treatment with trilostane. The dogs with PDH had significantly higher baseline and poststimulation concentrations of cortisol and cortisone, and higher baseline cortisol:cortisone ratios than the healthy dogs. During the treatment with trilostane, the poststimulation cortisol, the baseline and poststimulation cortisone concentrations, and the baseline and poststimulation cortisol:cortisone ratios decreased significantly. The decrease in poststimulation cortisone was significantly smaller than the decrease in cortisol.

  18. [Ear reconstruction using porous polyethylene implants. Effect of cortisone on edema reduction and healing process].

    Science.gov (United States)

    Naumann, A; Ehrmantraut, S; Willnecker, V; Menger, M D; Schick, B; Laschke, M W

    2011-03-01

    Porous polyethylene implants are increasingly used for ear reconstruction. Although the material used exhibits good biocompatibility, swelling and edema formation frequently occur after implantation, which may be treated by prophylactic cortisone therapy. The aim of the present study was to analyze the effects of cortisone therapy on the postoperative healing process. Between 2006 and 2010 porous polyethylene implants (Medpor®) were used for ear reconstruction of high-grade ear deformities in 23 patients (m:f=11:12; age: 17.2±12.4 years). For this purpose, 11 patients were treated systemically with cortisone (3 mg/kg body weight Solu-Decortin H) for the first 3 postoperative days, whereas 12 patients (controls) did not receive cortisone. Postoperatively, we analyzed the time course of edema formation, complications and the reconstructive result. Rejection or extrusion of the polyethylene implants was not observed in any of the patients (n=23) during a postoperative observation period of up to 3.5 years. Within 3-12 months after ear reconstruction all patients exhibited a completely shaped ear. Administration of cortisone had no significant effect on postoperative edema formation or the reconstructive end result. Porous polyethylene implants are well suited for the reconstruction of moderate to high-grade ear deformities. Since administration of cortisone does not significantly affect the postoperative healing process, prophylactic cortisone treatment following ear reconstruction with porous polyethylene implants should be omitted with regard to potential side effects.

  19. Cortisol and cortisone ratio in urine: LC-MS/MS method validation and preliminary clinical application.

    Science.gov (United States)

    Antonelli, Giorgia; Artusi, Carlo; Marinova, Mariela; Brugnolo, Laura; Zaninotto, Martina; Scaroni, Carla; Gatti, Rosalba; Mantero, Franco; Plebani, Mario

    2014-02-01

    The determination of urinary cortisol/cortisone ratio is of clinical utility in cases of Cushing's syndrome, apparent mineralocorticoid excess, and also provides information on 11β-hydroxysteroid dehydrogenase (11β-HSD) type 2 activity. It is therefore of utmost importance to ensure accurate cortisol and cortisone measurement and establish appropriate reference ranges. After the isotopic dilution of urine, sample cleanups were obtained with on-line solid-phase extraction and cortisol and cortisone, separated using a Zorbax Eclipse XDB-C18 HPLC analytical column, were analyzed by tandem mass spectrometry with an electrospray ionization source in positive ion mode operation. The method was linear, with concentrations of up to 625 and 1125 nmol/L and lower limit of quantitation (LLOQ) of 5 and 6 nmol/L, for cortisol and cortisone, respectively. Within-run and between-run coefficients of variation were cortisone, respectively. No ion suppression was observed. The non-parametric reference range for the cortisol/cortisone ratio was 0.14-1.09. A simple and sensitive liquid chromatography tandem mass spectrometry method was developed and validated for the measurement of cortisol and cortisone in urine. Our findings indicate that the proposed analytical method is suitable for routine purposes and useful in many pathological conditions.

  20. Breast-Milk Cortisol and Cortisone Concentrations Follow the Diurnal Rhythm of Maternal Hypothalamus-Pituitary-Adrenal Axis Activity.

    Science.gov (United States)

    van der Voorn, Bibian; de Waard, Marita; van Goudoever, Johannes B; Rotteveel, Joost; Heijboer, Annemieke C; Finken, Martijn Jj

    2016-11-01

    Very preterm infants often receive donor milk from mothers who deliver at term, but its composition differs from that of their own mother's milk. Because breast-milk glucocorticoids can support developing neonates, we explored concentration variability within and between mothers. We hypothesized that breast-milk glucocorticoid concentrations would be higher after very preterm delivery [gestational age (GA) cortisone, and the cortisone-to-(cortisol+cortisone) ratio of mothers who delivered at (median) GA: 28.6 wk or at term weekly during the first month postpartum. Study 2 assessed variations in milk cortisol, cortisone, and the cortisone-to-(cortisol+cortisone) ratio over 24 h, and tested Pearson correlations between milk and salivary concentrations in mothers who delivered at term (median GA: 38.9 wk) during week 4 postpartum. In these studies, foremilk glucocorticoids were measured by liquid chromatography-tandem mass spectrometry. Associations of milk cortisol, milk cortisone, and the milk cortisone-to-(cortisol+cortisone) ratio with prematurity (study 1) or collection time (study 2) were studied with longitudinal data analyses. In study 1, giving birth to a very preterm infant was associated with reductions in milk cortisol and cortisone concentrations of 50% (β: 0.50; 95% CI: 0.26, 0.99; P = 0.05) and 53% (β: 0.53; 95% CI: 0.30, 0.93; P = 0.03), respectively, when adjusted for collection time. In study 2, concentrations of milk cortisol and cortisone were associated with collection time (both P cortisone (r = 0.93, P cortisone-to-(cortisol+cortisone) ratio (r = 0.64, P < 0.01) were correlated with one another. Breast-milk glucocorticoid concentrations follow the diurnal rhythm of maternal hypothalamus-pituitary-adrenal axis activity and are lower in mothers who deliver very preterm. © 2016 American Society for Nutrition.

  1. Photocatalytic decomposition of cortisone acetate in aqueous solution

    Energy Technology Data Exchange (ETDEWEB)

    Romão, Joana Sobral; Hamdy, Mohamed S.; Mul, Guido, E-mail: g.mul@utwente.nl; Baltrusaitis, Jonas, E-mail: j.baltrusaitis@utwente.nl

    2015-01-23

    Graphical abstract: - Highlights: • Most efficient photocatalysts for cortisone 21-acetate (CA) degradation were ZnO and TiO{sub 2} (P25). • The decomposition rate increased at low CA concentrations. • No pH dependence was observed allowing CA photocatalytic degradation at native pH. • Synergistic CA degradation effects between TiO{sub 2} and S{sub 2}O{sub 8}{sup 2−} were found. • LC–MS confirmed a decrease in CA concentration, but no intermediate products were detected. - Abstract: The photocatalytic decomposition of cortisone 21-acetate (CA), a model compound for the commonly used steroid, cortisone, was studied. CA was photocatalytically decomposed in a slurry reactor with the initial rates between 0.11 and 0.46 mg L{sup −1} min{sup −1} at 10 mg L{sup −1} concentration, using the following heterogeneous photocatalysts in decreasing order of their catalytic activity: ZnO > Evonik TiO{sub 2} P25 > Hombikat TiO{sub 2} > WO{sub 3}. Due to the lack of ZnO stability in aqueous solutions, TiO{sub 2} P25 was chosen for further experiments. The decomposition reaction was found to be pseudo-first order and the rate constant decreased as a function of increasing initial CA concentration. Changing the initial pH of the CA solution did not affect the reaction rate significantly. The decomposition reaction in the presence of the oxidizing sacrificial agent sodium persulfate showed an observed decomposition rate constant of 0.004 min{sup −1}, lower than that obtained for TiO{sub 2} P25 (0.040 min{sup −1}). The highest photocatalytic degradation rate constant was obtained combining both TiO{sub 2} P25 and S{sub 2}O{sub 8}{sup 2−} (0.071 min{sup −1}) showing a synergistic effect. No reactive intermediates were detected using LC–MS showing fast photocatalytic decomposition kinetics of CA.

  2. RHEUMATOID ARTHRITIS—An Evaluation of Long-Term Treatment with Cortisone

    Science.gov (United States)

    Engleman, Ephraim P.; Krupp, Marcus A.; Saunders, William W.; Wilson, Lloyd E.; Fredell, Erling W.

    1954-01-01

    Fifty-six patients with rheumatoid arthritis were treated continuously with cortisone for periods ranging between 4 and 38 months, in daily doses of 15 to 100 mg. Concomitant therapy included periods of rest, physical therapy, and salicylates. The incidence of subjective improvement exceeded that of objective improvement. The incidence of objective improvement was higher in females; also, in those patients whose disease was in an early stage and of short duration at the time therapy was begun, and who required relatively smaller maintenance doses of cortisone. Therapeutic results were not affected by the age of the patient or by the presence of spondylitis. Despite precautions, the long-term administration of cortisone was, in some patients, productive of serious undesirable side-effects. Although cortisone usually suppressed the symptoms and signs of rheumatoid arthritis, progression of the disease was frequently noted during its long-term administration. ImagesFigure 1 PMID:13150213

  3. The effect of cortisone on the multiplication of M. tuberculosis in normal and immune mice

    Science.gov (United States)

    Robson, J. M.; Sullivan, F. M.

    1957-01-01

    The multiplication of M. tuberculosis, var. bovis inoculated into the cornea of mice was studied by staining the whole cornea at various stages after inoculation. Four groups of animals were studied: untreated animals, animals treated with cortisone, animals previously immunized with the same bovine strain, and immunized animals treated with cortisone. In the untreated immunized group little or no multiplication occurred. In the other three groups multiplication did occur and was about the same for the first week after inoculation. After this stage, cortisone-treated animals, whether previously immunized or not, showed increased multiplication and massive cord formation, as compared with untreated animals in which little further multiplication was seen. The cortisone treatment had thus completely suppressed immunity. The significance of these results is discussed. ImagesFIG. 1FIG. 2 PMID:13446380

  4. [Cortisone-induced humerus head necrosis in acute myeloid leukemia: cartilage-preserving arthroscopic spongioplasty].

    Science.gov (United States)

    Heid, A; Dickschas, J; Schoeffl, V

    2013-02-01

    Osteonecrosis is a long known side effect in patients receiving cortisone or chemotherapy. A young patient was diagnosed with acute myeloid leukemia (AML) in 2005. After receiving combined cortisone and chemotherapy the patient was in complete remission. In 2007 a total hip replacement was necessary due to femoral head necrosis. Years after the joint replacement the patient reported acute shoulder pain without trauma. In this article an alternative procedure to an endoprothesis in a young patient with a humeral head osteonecrosis is presented.

  5. Cortisone in hair of elementary school girls and its relationship with childhood stress.

    Science.gov (United States)

    Vanaelst, Barbara; Michels, Nathalie; De Vriendt, Tineke; Huybrechts, Inge; Vyncke, Krishna; Sioen, Isabelle; Bammann, Karin; Rivet, Noellie; Raul, Jean-Sebastien; Molnar, Denes; De Henauw, Stefaan

    2013-06-01

    Children may be exposed to stressful situations with adverse effects on their physiological and psychological health. As cortisone may be a useful additional biomarker for stress research and as it has been shown to be detectable in human hair, this study measured physiological concentrations of hair cortisone in 223 elementary school girls and explored its relationship with child-reported estimates of stress, more specifically questionnaires on major life events (i.e., Coddington Life Events Scale for Children), emotions (i.e., anger, anxiety, sadness, and happiness), and coping strategies (i.e., emotion- versus problem-focused coping). Cortisone concentrations were positively correlated with the overall life event score for the past 6 months (rho = 0.223, p = 0.004), as well as with the negative event score for this period (rho = 0.227, p = 0.003; N = 165). Cortisone did not correlate with emotions or coping styles reported by the children. Despite its exploratory nature, this study may suggest elevated hair cortisone concentrations under psychosocial stress in young children. Although the observed findings should be interpreted with prudence, this study may encourage further research elucidating the potential importance and relevance of hair cortisone analysis as an additional or substituting stress biomarker for hair cortisol.

  6. Effects of cortisone on H-2 agglutinin response in normal and thymectomized adult mice

    Science.gov (United States)

    Ramos, Alicia; Chacón, J.; Ferreira, A.; Hoecker, G.

    1973-01-01

    Cortisone suppresses circulating H-2 agglutinins when given prior to the injection of soluble cell extracts but not when the same antigens are given as cells. This same difference in antigen handling is observed in adult cortisone-treated thymectomized mice. Thus thymus as such is not involved in these differences in antigen handling. The spleen of adult thymectomized mice is as sensitive to cortisone as that of intact or sham-operated animals: after a strong initial drop in weight, the spleen recovers even during cortisone treatment in both intact and thymectomized mice. When a second cortisone treatment is given, the spleen loses about the same weight fraction as the first time in thymectomized and intact mice. These findings indicate that a fraction of either thymus or marrow-dependent lymphocytes differentiates in the spleen to become cortisone-sensitive. All these facts taken together show that antigen size per se is the main determining factor in antigen processing, i.e. the cellular path involved in antibody production. PMID:4706562

  7. Suppression of bovine lymphocyte function by treatment with physiologic concentrations of cortisone

    Energy Technology Data Exchange (ETDEWEB)

    Ojo-Amaize, E.A.; Paape, M.J.; Guidry, A.J.; Mayer, H.K.

    1986-03-01

    The blastogenic response of peripheral blood lymphocytes (PBL) (8 cows) to capsular antigen extract of Staphylococcus aureus, PHA and LPS was measured in vitro using /sup 5/H-thymidine pulse labelling. isolated PBL were treated in vitro for 6-8 days with 10, 25 and 45 ng/ml cortisone. These concentrations simulate serum corticosteroid levels during environmental stress, acute clinical mastitis and ACTH therapy, respectively. To determine the minimal concentration of cortisone that would induce suppression, PBL were also incubated with increasing concentrations of cortisone starting at 10 pg/ml. All concentrations of cortisone caused a significant (P<0.01) depression of lymphocyte blastogenic response to S. aureus, PHA and LPS. Macrophage depletion experiments showed no macrophage suppressor effects. Both the blastogenic response of untreated peripheral blood lymphocytes to S. aureus, PHA and LPS and the degree to which that response was suppressed by cortisone differed significantly among cows. Results indicate that cortisone levels found during physiological stress and after therapeutic administration of ACTH can suppress lymphocyte function.

  8. Cortisone and dexamethasone inhibit myogenesis by modulating the AKT/mTOR signaling pathway in C2C12

    National Research Council Canada - National Science Library

    Kim, Jonggun; Park, Min Young; Kim, Hyung Kwan; Park, Yeonhwa; Whang, Kwang-Youn

    2016-01-01

    .... The action of glucocorticoids on differentiated skeletal muscle was well studied, but their effects on myotube formation have not been well investigated. Dexamethasone (DEX) and cortisone (COR...

  9. Salivary but not plasma cortisone tracks the plasma cortisol response to exercise: effect of time of day.

    Science.gov (United States)

    Del Corral, P; Schurman, R C; Kinza, S S; Fitzgerald, M J; Kordick, C A; Rusch, J L; Nadolski, J B

    2016-03-01

    The cortisol, cortisone, corticosterone, and CBG responses to exercise in the AM and PM have not been described. This study examined the response of these glucocorticoids and CBG to intense exercise in 12 endurance-trained men in plasma (Pl) and saliva (Sa). Each subject completed treadmill exercise in the morning and evening. Paired blood and Sa samples were obtained at rest before and after exercise. Significant time effect existed for Pl-cortisol and Sa-cortisol from baseline in the AM and PM (p cortisone and CBG significantly increased in the PM (p cortisone, Sa-cortisone was significantly higher in the AM compared to the PM, increasing in the AM and PM (All p cortisone (r = 0.81, p cortisone (~90 %) and corticosterone (~200 %) in the AM and PM, whereas exercise increases CBG in the PM, but not in the AM; (2) vigorous exercise increases Sa-cortisone; (3) Sa-cortisone and cortisol are equally strongly correlated to Pl-cortisol, suggesting a significant role for Sa-cortisone as a novel marker of free cortisol during exercise.

  10. Inhibitory effects of cortisone and hydrocortisone on human Kv1.5 channel currents.

    Science.gov (United States)

    Yu, Jing; Park, Mi-Hyeong; Jo, Su-Hyun

    2015-01-05

    Glucocorticoids are the primary hormones that respond to stress and protect organisms from dangerous situations. The glucocorticoids hydrocortisone and its dormant form, cortisone, affect the cardiovascular system with changes such as increased blood pressure and cardioprotection. Kv1.5 channels play a critical role in the maintenance of cellular membrane potential and are widely expressed in pancreatic β-cells, neurons, myocytes, and smooth muscle cells of the pulmonary vasculature. We examined the electrophysiological effects of both cortisone and hydrocortisone on human Kv1.5 channels expressed in Xenopus oocytes using a two-microelectrode voltage clamp technique. Both cortisone and hydrocortisone rapidly and irreversibly suppressed the amplitude of Kv1.5 channel current with IC50 values of 50.2±4.2μM and 33.4±3.2μM, respectively, while sustained the current trace shape of Kv1.5 current. The inhibitory effect of cortisone on Kv1.5 decreased progressively from -10mV to +30mV, while hydrocortisone׳s inhibition of the channel did not change across the same voltage range. Both cortisone and hydrocortisone blocked Kv1.5 channel currents in a non-use-dependent manner and neither altered the channel׳s steady-state activation or inactivation curves. These results show that cortisone and hydrocortisone inhibited Kv1.5 channel currents differently, and that Kv1.5 channels were more sensitive to hydrocortisone than to cortisone. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Cortisol/cortisone ratio and matrix metalloproteinase-9 activity are associated with pediatric primary hypertension.

    Science.gov (United States)

    Martinez-Aguayo, Alejandro; Campino, Carmen; Baudrand, Rene; Carvajal, Cristian A; García, Hernán; Aglony, Marlene; Bancalari, Rodrigo; García, Lorena; Loureiro, Carolina; Vecchiola, Andrea; Tapia-Castillo, Alejandra; Valdivia, Carolina; Sanhueza, Sebastian; Fuentes, Cristobal A; Lagos, Carlos F; Solari, Sandra; Allende, Fidel; Kalergis, Alexis M; Fardella, Carlos E

    2016-09-01

    To identify novel biomarkers associated with pediatric primary hypertension. We recruited 350 participants (4-16 years). Anthropometric parameters and aldosterone, plasma renin activity, cortisol, cortisone, Homeostasis Model Assessment Insulin Resistance (HOMA-IR), high-sensitivity C-reactive protein, adiponectin, IL-6, plasminogen activator inhibitor type 1 levels and matrix metalloproteinase-9 and matrix metalloproteinase-2 (MMP-9 and MMP-2) activities were measured. Genomic DNA was isolated. Patients with altered glucose metabolism, severe obesity [BMI-SD score (BMI-SDS) > 2.5], renovascular disease, primary aldosteronism and apparent mineralocorticoid excess syndrome were excluded. In selected participants (n = 320), SBP was positively correlated with BMI-SDS (r = 0.382, P cortisone ratio (r = 0.231, P cortisone ratio (P cortisone ratio (OR = 3.92; 95% CI = 1.98-7.71) and increased MMP-9 activity (OR = 4.23; 95% CI = 2.15-8.32). We report that MMP-9 activity and the cortisol/cortisone ratio were higher in pediatric primary hypertensive patients, and these associations were independent of the effect of obesity. The potential role of these novel biomarkers in predicting hypertension risk and blood pressure regulation warrants further investigation.

  12. Cortisone and hydrocortisone inhibit human Kv1.3 activity in a non-genomic manner.

    Science.gov (United States)

    Yu, Jing; Park, Mi-Hyeong; Choi, Se-Young; Jo, Su-Hyun

    2015-06-01

    Glucocorticoids are hormones released in response to stress that are involved in various physiological processes including immune functions. One immune-modulating mechanism is achieved by the Kv1.3 voltage-dependent potassium channel, which is expressed highly in lymphocytes including effector memory T lymphocytes (TEM). Although glucocorticoids are known to inhibit Kv1.3 function, the detailed inhibitory mechanism is not yet fully understood. Here we studied the rapid non-genomic effects of cortisone and hydrocortisone on the human Kv1.3 channel expressed in Xenopus oocytes. Both cortisone and hydrocortisone reduced the amplitude of the Kv1.3 channel current in a concentration-dependent manner. Both cortisone and hydrocortisone rapidly and irreversibly inhibited Kv1.3 currents, eliminating the possibility of genomic regulation. Inhibition rate was stable relative to the degree of depolarization. Kinetically, cortisone altered the activating gate of Kv1.3 and hydrocortisone interacted with this channel in an open state. These results suggest that cortisone and hydrocortisone inhibit Kv1.3 currents via a non-genomic mechanism, providing a mechanism for the immunosuppressive effects of glucocorticoids.

  13. [Cortisone Acetate Reference Standard (Control 921) of National Institute of Health Sciences].

    Science.gov (United States)

    Izumi, W; Kitajima, A; Yoshii, K; Komatsu, H; Ishimitsu, S; Okada, S

    1993-01-01

    The raw material of cortisone acetate was tested for the preparation of "Cortisone Acetate Reference Standard (Control 921)". The quality of the raw material was examined and compared with the previous Cortisone Acetate Reference Standard (Control 743). Analytical data obtained were as follows: loss on drying, 0.06%; melting point, 245.9 degrees C (decomposition); optical rotation, [alpha]20D = +215.5 degrees; UV spectrum, lambda max = 239 nm and specific absorbance E 1%1 cm (239 nm) = 393; infrared spectrum, the same as that of the previous Reference Standard (Control 743); thin-layer chromatography, no impurities were detected up to 100 micrograms; high-performance liquid chromatography (HPLC), three impurities were detected; assay, 100.5% by HPLC. Based on the above results, the raw material was authorized as the Japanese Pharmacopoeia Reference Standard (Control 921).

  14. Determinants of hair cortisol and hair cortisone concentrations in adults.

    Science.gov (United States)

    Staufenbiel, Sabine M; Penninx, Brenda W J H; de Rijke, Yolanda B; van den Akker, Erica L T; van Rossum, Elisabeth F C

    2015-10-01

    The analysis of hair cortisol concentrations (HairF) is a promising new tool for the assessment of long-term cortisol. With the development of multiple steroid analyses by means of liquid chromatography tandem-mass spectrometry (LC-MS/MS), the analysis of cortisone in hair (HairE) has also been facilitated. However, the influence of various types of determinants on HairF and HairE is still largely unknown. This study systematically assesses the influence of sociodemographic, health, lifestyle, and hair (treatment) characteristics on HairF and HairE. Data of 760 psychiatrically healthy participants (71.8% female, mean age 45.89 years) of the Netherlands Study of Depression and Anxiety (NESDA) were used. HairF and HairE were measured in the proximal 3 cm of scalp hair, using LC-MS/MS. HairF and HairE strongly correlated. In simple linear regressions, HairF and HairE were higher in older age, in presence of diabetes mellitus, and in men compared to women. More frequent washing of the hair was associated with lower HairF and HairE. Darker hair colours were associated with higher HairF and HairE. An effect of season and of use of oral contraceptives was found for HairF. After full mutual adjustment, only age, presence of diabetes mellitus, hair washing frequency, and season remained significant determinants of HairF. This large-scale study shows that HairF and HairE are upregulated in older age and in the presence of diabetes mellitus. This suggests that these levels are important for somatic health and should be taken into account when using hair corticosteroid analysis in future studies. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Recycling between cortisol and cortisone in human splanchnic, subcutaneous adipose, and skeletal muscle tissues in vivo.

    Science.gov (United States)

    Hughes, Katherine A; Manolopoulos, Konstantinos N; Iqbal, Javaid; Cruden, Nicholas L; Stimson, Roland H; Reynolds, Rebecca M; Newby, David E; Andrew, Ruth; Karpe, Fredrik; Walker, Brian R

    2012-06-01

    11β-Hydroxysteroid dehydrogenase type 1 (11βHSD1) is a therapeutic target in metabolic syndrome because it catalyses reductase regeneration of cortisol from cortisone in adipose and liver. 11βHSD1 can also catalyze the reverse dehydrogenase reaction in vitro (e.g., if cofactor is limited). We used stable isotope tracers to test the hypothesis that both 11βHSD1-reductase and -dehydrogenase activities occur in human metabolic tissues in vivo. 1,2-[(2)H](2)-Cortisone (d2-cortisone) was validated as a tracer for 11β-dehydrogenase activity and its inhibition by licorice. d2-Cortisone and 9,11,12,12-[(2)H](4)-cortisol (d4-cortisol) (to measure 11β-reductase activity) were coinfused and venous samples obtained from skeletal muscle, subcutaneous adipose (n = 6), and liver (n = 4). Steroids were measured by liquid chromatography-tandem mass spectrometry and arteriovenous differences adjusted for blood flow. Data are means ± SEM. 11β-Reductase and -dehydrogenase activities were detected in muscle (cortisol release 19.7 ± 4.1 pmol/100 mL/min, d3-cortisol 5.9 ± 1.8 pmol/100 mL/min, and cortisone 15.2 ± 5.8 pmol/100 mL/min) and splanchnic (cortisol 64.0 ± 11.4 nmol/min, d3-cortisol 12.9 ± 2.1 nmol/min, and cortisone 19.5 ± 2.8 nmol/min) circulations. In adipose, dehydrogenase was more readily detected than reductase (cortisone release 38.7 ± 5.8 pmol/100 g/min). Active recycling between cortisol and cortisone in metabolic tissues in vivo may facilitate dynamic control of intracellular cortisol but makes consequences of dysregulation of 11βHSD1 transcription in obesity and diabetes unpredictable. Disappointing efficacy of 11βHSD1 inhibitors in phase II studies could be explained by lack of selectivity for 11β-reductase.

  16. Determination of cortisol and cortisone in urine using high-performance liquid chromatography with UV detection.

    Science.gov (United States)

    Jenner, D A; Richards, J

    1985-01-01

    The application of reversed-phase gradient high-performance liquid chromatography with UV detection to the determination of cortisol and cortisone in 24-h urine samples is described. The method employs Sep-pak C18 cartridges for the part-purification and concentration of the corticosteroids, with sample enrichment at the head of an HPLC pre-column and separation using water/acetonitrile gradient. The internal standard is 6alpha-methylprednisolone. Measurement of both cortisone and cortisol provides further information on adrenocortical function. 24-hour excretion rate data from normal subjects are reported.

  17. Hair cortisone level is associated with PTSD׳s dysphoric arousal symptoms in highly traumatized Chinese females.

    Science.gov (United States)

    Wang, Weiwen; Deng, Huihua; Wang, Li; Cao, Chengqi; Xu, Hang; Zhang, Jianxin

    2015-08-15

    Cortisone has been proposed as a useful additional biomarker for stress research. However, only very limited studies has investigated alterations of cortisone levels in stress-related mental disorder such as PTSD. The present study investigated the associations between PTSD symptomatology and hair cortisone levels which can reflect cumulative cortisone secretion over prolonged periods of time and is more robust to the influence of situational confounding. Participants included 201 females who experienced 2008 Wenchuan earthquake and lost their children during the disaster. PTSD symptoms were assessed with the PTSD Checklist (PCL), and depression symptoms with the Center for epidemiological studies depression scale (CES-D). Hair cortisone levels were quantified by liquid chromatography tandem mass spectrometer. The results indicated that although hair cortisone secretion could not distinguish traumatized individuals with and without PTSD, it was uniquely linked to dysphoric arousal symptoms, a key aspect of the complex PTSD phenotype A sample of females exposed to specific traumatic events was used, and PTSD was assessed using a self-reported measure. The findings provide preliminary evidence supporting the critical role of long-term cortisone changes in the development and maintenance of PTSD symptoms, and add to extant knowledge on the neuroendocrinological underpinnings of posttraumatic psychopathology. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Cortisone dissociates voltage-dependent K+ channel from its beta subunit

    Science.gov (United States)

    Pan, Yaping; Weng, Jun; Kabaleeswaran, Venkataraman; Li, Huiguang; Cao, Yu; Bhosle, Rahul C.; Zhou, Ming

    2009-01-01

    The Shaker family voltage-dependent potassium channels (Kv1) are expressed in a wide variety of cells and essential for cellular excitability. In humans, loss-of-function mutations of Kv1 channels lead to hyperexcitability and are directly linked to episodic ataxia and atrial fibrillation. All Kv1 channels assemble with beta subunits (Kvβ) and certain Kvβs, for example Kvβ1, have an N-terminal segment that closes a channel by the N-type inactivation mechanism. In principle dissociation of Kvβ1, although never reported, should eliminate inactivation and thus potentiate Kv1 current. We found that cortisone increases mammalian (rat) Kv1 channel activity by binding to Kvβ1. A crystal structure of the Kvβ-cortisone complex was solved to 1.82 Å resolution and revealed novel cortisone binding sites. Further studies demonstrated that cortisone promotes dissociation of Kvβ. The new mode of channel modulation may be explored by native or synthetic ligands to fine tune cellular excitability. PMID:18806782

  19. Potentiation of the Kv1 family K(+) channel by cortisone analogues.

    Science.gov (United States)

    Pan, Yaping; Levin, Elena J; Quick, Matthias; Zhou, Ming

    2012-10-19

    The Kv1 family voltage-dependent K(+) channels are essential for termination of action potentials in neurons and myocytes. These channels form a stable complex with their beta subunits (Kvβ), some of which inhibit channel activity. Cortisone potentiates Kv1 channel by binding to Kvβ and promoting its dissociation from the channel, but its half-maximum effective concentration is ∼46 μM. To identify corticosteroids that are more efficient than cortisone, we examined 25 cortisone analogues and found that fluticasone propionate potentiates channel current with a half-maximum effective concentration (EC(50)) of 37 ± 1.1 nM. Further studies showed that fluticasone propionate potentiates channel current by inducing dissociation of Kvβ, and docking of fluticasone propionate into the cortisone binding site reveals potential interactions that enhance the EC(50) value. Thus, fluticasone propionate provides a starting point for rational design of more efficient small-molecule compounds that increase Kv1 activity and affect the integrity of the Kv1-Kvβ complex.

  20. Potentiation of the Kv1 family K+ channel by cortisone analogs

    Science.gov (United States)

    Pan, Yaping; Levin, Elena J.; Quick, Matthias; Zhou, Ming

    2013-01-01

    The Kv1 family voltage-dependent K+ channels are essential for termination of action potentials in neurons and myocytes. These channels form a stable complex with their beta subunits (Kvβ), some of which inhibit channel activity. Cortisone potentiates Kv1 channel by binding to Kvβ and promoting its dissociation from the channel, but its half-maximum effective concentration is ~46 μM. To identify corticosteroids that are more efficient than cortisone, we examined 25 cortisone analogs and found that fluticasone propionate potentiates channel current with a half-maximum effective concentration (EC50) of 37 ± 1.1 nM. Further studies showed that fluticasone propionate potentiates channel current by inducing dissociation of Kvβ, and docking of fluticasone propionate into the cortisone binding site reveals potential interactions that enhance the EC50 value. Thus, fluticasone propionate provides a starting point for rational design of more efficient small-molecule compounds that increase Kv1 activity and affect the integrity of the Kv1-Kvβ complex. PMID:22803826

  1. Cortisone Dissociates the Shaker Family K Channels from their Beta Subunit

    Energy Technology Data Exchange (ETDEWEB)

    Pan, Y.; Weng, J; Kabaleeswaran, V; Li, H; Cao, Y; Bholse, R; Zhou, M

    2008-01-01

    The Shaker family voltage-dependent potassium channels (Kv1) are expressed in a wide variety of cells and are essential for cellular excitability. In humans, loss-of-function mutations of Kv1 channels lead to hyperexcitability and are directly linked to episodic ataxia and atrial fibrillation. All Kv1 channels assemble with {Beta} subunits (Kv{Beta}s), and certain Kv{Beta}s, for example Kv{Beta}1, have an N-terminal segment that closes the channel by the N-type inactivation mechanism. In principle, dissociation of Kv{Beta}1, although never reported, should eliminate inactivation and thus potentiate Kv1 current. We found that cortisone increases rat Kv1 channel activity by binding to Kv{Beta}1. A crystal structure of the K{Beta}v-cortisone complex was solved to 1.82-{angstrom}resolution and revealed novel cortisone binding sites. Further studies demonstrated that cortisone promotes dissociation of Kv{Beta}. The new mode of channel modulation may be explored by native or synthetic ligands to fine-tune cellular excitability.

  2. The effect of subacromial injections of autologous conditioned plasma versus cortisone for the treatment of symptomatic partial rotator cuff tears.

    Science.gov (United States)

    von Wehren, Lutz; Blanke, Fabian; Todorov, Atanas; Heisterbach, Patricia; Sailer, Jannis; Majewski, Martin

    2016-12-01

    Rotator cuff tears are one of the most common causes of shoulder malfunction and pain, which lead to a significant reduction in the quality of life. This present study investigated the effects of subacromial platelet-rich plasma injections [i.e. autologous conditioned plasma (ACP) injections] as compared to standard subacromial cortisone injection therapy in 50 patients with partial rotator cuff tears. Before injection, and 6 weeks, 12 weeks and 6 months thereafter, the patients were assessed by the Constant-Murley score (CMS), the American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES), the simple shoulder test (SST) and a pain visual analogue scale (VAS). An MRI was also performed before and 6 months after injection. Both patient groups had statistically significant better shoulder score outcomes over time. ASES, SST and CMS outcomes after 12 versus 6 weeks were better in the ACP group as compared to the cortisone group. VAS, ASES and CMS outcomes after 12 weeks versus baseline in the ACP group were better as compared to the cortisone group. There was a statistically significant difference between ACP group and cortisone group 12 weeks after injection regarding VAS, ASES, SST and CMS in favour of the ACP group. The MRI showed an improvement in grade of tendinopathy in both groups, however, without statistically significant differences between the two groups. Compared with cortisone injections, ACP injections show earlier benefit as compared to cortisone injections although a statistically significant difference after 6 months could not be found. Therefore, subacromial ACP injections are a good alternative to subacromial cortisone injections, especially in patients with contraindication to cortisone. Therapeutic study, Level III.

  3. Simultaneous measurement of endogenous cortisol, cortisone, dehydroepiandrosterone, and dehydroepiandrosterone sulfate in nails by use of UPLC-MS-MS.

    Science.gov (United States)

    Ben Khelil, Mehdi; Tegethoff, Marion; Meinlschmidt, Gunther; Jamey, Carole; Ludes, Bertrand; Raul, Jean-Sébastien

    2011-09-01

    Steroid hormone concentrations are mostly determined by using different body fluids as matrices and applying immunoassay techniques. However, usability of these approaches may be restricted for several reasons, including ethical barriers to invasive sampling. Therefore, we developed an ultra-performance LC-MS-MS method for high-throughput determination of concentrations of cortisol, cortisone, dehydroepiandrosterone (DHEA), and DHEA sulfate (DHEAS) in small quantities of human nails. The method was validated for linearity, limits of detection and quantification, recovery, intra and interassay precision, accuracy, and matrix effect. Samples from 10 adult women were analyzed to provide proof-of-principle for the method's applicability. Calibration curves were linear (r(2) > 0.999) in the ranges 10-5000 pg mg(-1) for cortisol, cortisone, and DHEAS, and 50-5000 pg mg(-1) for DHEA. Limits of quantification were 10 pg mg(-1) for cortisol, cortisone, and DHEAS, and 50 pg mg(-1) for DHEA. The sensitivity and specificity of the method were good, and there was no interference with the analytes. Mean recovery of cortisol, cortisone, DHEA, and DHEAS was 90.5%, 94.1%, 84.9%, and 95.9%, respectively, with good precision (coefficient of variation cortisone, DHEA, and DHEAS, respectively. This method enables measurement of cortisol, cortisone, DHEA, and DHEAS in small quantities of human nails, leading to the development of applications in endocrinology and beyond.

  4. Micro determination of cortisol and cortisone in umbilical cord blood by chemiluminescent high-performance liquid chromatography.

    Science.gov (United States)

    Hasegawa, Takeshi; Kubo, Hiroaki; Shinozaki, Koichi; Nowatari, Masahiko; Ishii, Masahiro

    2010-06-01

    A simple, sensitive and specific chemiluminescent high-performance liquid chromatography method, based on the luminol reaction, for determination of serum cortisol and cortisone, was established. In infants, placental 11beta-hydroxysteroid dehydrogenase type 2 enzyme (11beta-HSD2) activity may affect adrenal function early after birth. The cortisol-cortisone ratio of serum concentrations in umbilical cord blood is an indicator of placental 11beta-HSD2 activity. The optimum conditions for the luminol reaction were determined to be 1.5 mM luminol, 0.6 M sodium hydroxide, 0.15 mm potassium hexacyanoferrate(III) and 200 mM potassium hexacyanoferrate (II). The calibration curves for cortisol and cortisone exhibited good linearity. The correlation coefficients of the calibration curves were 0.996. The intra- and inter-day precisions were in the ranges: cortisol 7.0-12.2 and 4.4-9.2%, cortisone 5.3-7.0 and 6.2-9.9%. The recoveries of these steroids were in the ranges: cortisol 97-105%, cortisone 94-102%. The limits of detection were as follows: cortisol, 0.17 microg/dl; cortisone 0.15 microg/dl. This assay could be successfully applied to determination of the cortisol-cortiosone ratio of serum concentrations in umbilical cord bloods. Copyright 2009 John Wiley & Sons, Ltd.

  5. Trichinella spiralis: differences between early and late rapid expulsion evident from inhibition studies using cortisone and irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Bell, R.G.

    1987-12-01

    Cortisone administered once at 100 mg/kg during the first 3 weeks of infection inhibited rapid expulsion. In rats immunized with an abbreviated infection (T/M regime) inhibition averaged approximately 50%, whereas in rats given a complete infection (C.I.) 14% inhibition occurred. Sensitivity to 400 rad whole-body irradiation was greatest 7 days before a challenge infection in all immune rats. Three days after beginning the T/M infection rats were highly susceptible to cortisone but only weakly so to irradiation. Rats immunized by C.I. were equally, but only weakly, susceptible to either cortisone or irradiation 3 days after infection. Acute administration of cortisone 1 or 4 hr prior to challenge did not inhibit rapid expulsion but 60% inhibition occurred when cortisone was given 24 hr prior to challenge. Inhibition of rapid expulsion by irradiation 7 days prior to challenge was not reversed by immune serum and irradiation did not affect antibody titer in treated rats. It was suggested that irradiation 7 days before challenge compromised the intestinal, and not the immunological, component of rapid expulsion. Differences in sensitivity of early and late rapid expulsion to irradiation and cortisone therapy provide further evidence of functional differences between these rejection processes.

  6. Simultaneous quantification of cortisol and cortisone in urines from infants with packed-fiber solid-phase extraction coupled to HPLC-MS/MS.

    Science.gov (United States)

    Li, Chen; Zhang, Zhao; Liu, Xiongwei; Shen, Kangwei; Gu, Pan; Kang, Xuejun

    2017-09-01

    Cortisol and cortisone are two important glucocorticoids in human body, their interconversion is controlled by two isotypes of 11β-hydroxy steroid dehydrogenase (11β-HSD1 and 11β-HSD2). The ratio of urinary cortisol to cortisone can be used to assess the activity of 11β-HSDs. An analytical method to quantify urinary cortisol and cortisone using high performance liquid chromatographic tandem mass spectrometry following a packed-fiber solid-phase extraction (PFSPE) was developed. The proposed method was validated and applied to determine the urinary cortisol and cortisone concentrations in infants. Linearity was observed in the range of 0.6-150ng/mL for cortisol and 0.8-200ng/mL for cortisone. The intra-day RSD was 2.4-4.5% for cortisol and 3.3-6.2% for cortisone. Inter-day RSD was 3.7-6.6% for cortisol and 4.3-8.2% for cortisone. The recovery was 97.8±4.6% for cortisol and 98.9±4.4% for cortisone. The established method is simple and efficient for the quantification of urinary cortisol and cortisone and for indirectly assessing the activity of 11β-hydroxy steroid dehydrogenase. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Cyclic utilization of HP-β-CD in the bioconversion of cortisone acetate by Arthrobacter simplex.

    Science.gov (United States)

    Shen, Yanbing; Wang, Fang; Wang, Yanping; Zhao, Qing; Wang, Min

    2016-04-01

    To establish a method for the recovery and reutilization of hydroxypropyl-β-cyclodextrin (HP-β-CD) to lower the cost of its industrial application in cortisone acetate bioconversion. HP-β-CD is not degraded by Arthrobacter simplex CPCC140451 (ASP) resting cells and 96.4 % HP-β-CD could be recovered by isobutyl acetate extraction. Moreover, the inclusion ability of recovered HP-β-CD barely decreased. The saccharide metabolic and catalytic activities of ASP were greater in the aqueous phase after extracting with isobutyl acetate than other organic solvents. Cyclic utilization tests showed that cortisone acetate conversion ratio was 91.0 % after eight cycles and reached 95.7 % with 0.2-0.6 mM HP-β-CD. Furthermore, >90 % conversion ratio was reached per cycle through a co-cyclic-utilization method with HP-β-CD and immobilized ASP. Cortisone acetate conversion ratio in the HP-β-CD cyclic-utilization method is promising for industrial applications. The method can also be expanded to other CDs and other hydrophobic compounds bioconversion.

  8. Tandem mass spectrometry determined maternal cortisone to cortisol ratio and psychiatric morbidity during pregnancy-interaction with birth weight.

    Science.gov (United States)

    Hellgren, Charlotte; Edvinsson, Åsa; Olivier, Jocelien D; Fornes, Romina; Stener-Victorin, Elisabet; Ubhayasekera, S J Kumari A; Skalkidou, Alkistis; Bergquist, Jonas; Sundström-Poromaa, Inger

    2016-07-01

    Maternal serum cortisol has been suggested to be influenced by psychiatric morbidity, and may also influence fetal growth. However, several studies found equal cortisol levels in depressed and healthy pregnant women. Placental 11-β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) shields the fetus from maternal cortisol by conversion to cortisone, a function that may be compromised by maternal stress. We aimed to compare the serum ratio of cortisone to cortisol, in women with and without psychiatric morbidity during pregnancy. A secondary aim was to investigate whether fetal growth, approximated by infant birth weight, was associated with the cortisone to cortisol ratio. We performed tandem mass spectrometry analysis of serum cortisol and cortisone in late pregnancy in 94 women with antenatal psychiatric morbidity and 122 controls (cohort 1). We also compared the placental gene expression of HSD11B1 and 2 in another group of 69 women with psychiatric morbidity and 47 controls (cohort 2). There were no group differences in cortisol to cortisone ratio, absolute levels of cortisone and cortisol (cohort 1), or expression of HSD11B1 or 2 (cohort 2). However, cortisone to cortisol ratio was positively associated with birth weight in women with psychiatric morbidity, also after adjustment for gestational length, fetal sex, maternal height, smoking, SSRI use, and time of blood sampling (standardized β=0.35, pcortisone to cortisol ratio does not seem to be affected by psychiatric morbidity, but psychiatric morbidity may increase fetal exposure to cortisol or other metabolic factors influencing fetal growth. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  9. The effects of growth hormone deficiency and replacement on glucocorticoid exposure in hypopituitary patients on cortisone acetate and hydrocortisone replacement.

    Science.gov (United States)

    Swords, F M; Carroll, P V; Kisalu, J; Wood, P J; Taylor, N F; Monson, J P

    2003-11-01

    11 beta-hydroxysteroid dehydrogenase type 1 (11 beta HSD1) converts inactive cortisone to active cortisol. 11 beta HSD1 activity is increased in GH deficiency and inhibited by GH and IGF-I in acromegaly. However it is not known whether these changes in cortisol metabolism exert significant effects during hydrocortisone therapy, and the effect has not been studied in patients taking cortisone acetate. We have studied the effect of GH induced 11 beta HSD1 inhibition in hypopituitary adults with severe GH deficiency to determine whether this inhibition has a different magnitude of effect when patients are taking different forms of glucocorticoid replacement therapy. We have taken the ratio of 11-hydroxy/11-oxo cortisol metabolites (Fm/Em), an established measure of net 11 beta HSD activity to reflect the likely balance of cortisol to cortisone exposure in tissues expressing 11 beta HSD1, principally the liver and adipose tissue. We recruited 10 hypopituitary adults all on established glucocorticoid replacement therapy, but who were not receiving GH. Patients were treated with their standard hydrocortisone therapy for one week and an equivalent dose of cortisone acetate in its place for one week in random order. Serial serum cortisol assessments and urine steroid profiles were performed on each treatment. All patients were then established on GH therapy for at least three months before the two-week cycle was repeated. Fm/Em was also measured in a control population (20F, 20M). Prior to GH, the ratio Fm/Em was greater with hydrocortisone compared with cortisone acetate replacement (1.17 +/- 0.28 and 0.52 +/- 0.09 respectively, P cortisol/cortisone did not change indicating unchanged 11 beta HSD2 activity. Mean circulating cortisol also fell in all subjects after GH. This effect was greater during cortisone acetate treatment (-18.7%, P tissue exposure to glucocorticoid is supra-physiological in hypopituitary patients with untreated GH deficiency taking hydrocortisone

  10. Absence of 11-keto reduction of cortisone and 11-ketotestosterone in the model organism zebrafish.

    Science.gov (United States)

    Tsachaki, Maria; Meyer, Arne; Weger, Benjamin; Kratschmar, Denise V; Tokarz, Janina; Adamski, Jerzy; Belting, Heinz-Georg; Affolter, Markus; Dickmeis, Thomas; Odermatt, Alex

    2017-02-01

    Zebrafish are widely used as model organism. Their suitability for endocrine studies, drug screening and toxicity assessements depends on the extent of conservation of specific genes and biochemical pathways between zebrafish and human. Glucocorticoids consist of inactive 11-keto (cortisone and 11-dehydrocorticosterone) and active 11β-hydroxyl forms (cortisol and corticosterone). In mammals, two 11β-hydroxysteroid dehydrogenases (11β-HSD1 and 11β-HSD2) interconvert active and inactive glucocorticoids, allowing tissue-specific regulation of glucocorticoid action. Furthermore, 11β-HSDs are involved in the metabolism of 11-oxy androgens. As zebrafish and other teleost fish lack a direct homologue of 11β-HSD1, we investigated whether they can reduce 11-ketosteroids. We compared glucocorticoid and androgen metabolism between human and zebrafish using recombinant enzymes, microsomal preparations and zebrafish larvae. Our results provide strong evidence for the absence of 11-ketosteroid reduction in zebrafish. Neither human 11β-HSD3 nor the two zebrafish 11β-HSD3 homologues, previously hypothesized to reduce 11-ketosteroids, converted cortisone and 11-ketotestosterone (11KT) to their 11β-hydroxyl forms. Furthermore, zebrafish microsomes were unable to reduce 11-ketosteroids, and exposure of larvae to cortisone or the synthetic analogue prednisone did not affect glucocorticoid-dependent gene expression. Additionally, a dual-role of 11β-HSD2 by inactivating glucocorticoids and generating the main fish androgen 11KT was supported. Thus, due to the lack of 11-ketosteroid reduction, zebrafish and other teleost fish exhibit a limited tissue-specific regulation of glucocorticoid action, and their androgen production pathway is characterized by sustained 11KT production. These findings are of particular significance when using zebrafish as a model to study endocrine functions, stress responses and effects of pharmaceuticals. © 2017 Society for Endocrinology.

  11. Diffusion-weighted MR imaging of fetal lung maturation in sheep: effect of prenatal cortisone administration on ADC values.

    Science.gov (United States)

    Much, Chressen Catharina; Schoennagel, Björn Phillip; Yamamura, Jin; Buchert, Ralph; Kooijman, Hendrik; Schätzle, Anne-Kathrin; Adam, Gerhard; Wedegaertner, Ulrike

    2013-07-01

    To assess changes in diffusion properties in the fetal lung after cortisone administration with diffusion-weighted imaging (DWI) in fetal sheep. DWI was performed on 11 pregnant sheep with singleton pregnancies on a 1.5-T MRI scanner. Four animals received cortisone injections before baseline imaging. Seven animals served as controls. Apparent diffusion coefficient (ADC) was measured on DWI in the fetal lungs by two independent readers. The Pearson test was used to correlate ADC and gestational age. A t-test was performed to compare differences in ADC values at the baseline and follow-up images within and between groups. Inter-rater reliability was calculated. In the cortisone group, ADC values increased about 10 % between the baseline and follow-up images (P = 0.039). Comparing the cortisone and control groups, ADC values of the baseline images did not differ; whereas in the follow-up imaging, ADC values were significantly higher in the cortisone group (P = 0.024). Lung ADC values did not correlate with gestational age (P = 0.970). Inter-rater reliability was high (0.970, P = 0.000). In this experimental model, MR-DWI can detect cortisone-induced changes in diffusion properties of the fetal lung. • Corticosteroids are frequently administered antenatally to prevent fetal lung immaturity at birth • DWI can detect changes in the fetal lung after corticosteroid administration • Changes can be detected as early as 5 days after treatment • Fetal MRI may offer a non-invasive method of monitoring lung maturation.

  12. Simultaneous analysis of cortisol and cortisone in saliva using XLC-MS/MS for fully automated online solid phase extraction.

    Science.gov (United States)

    Jones, Rachel L; Owen, Laura J; Adaway, Joanne E; Keevil, Brian G

    2012-01-15

    Salivary cortisol measurements are increasingly being used in the investigation of disorders of the hypothalamic-pituitary-adrenal axis. In the salivary gland, cortisol is metabolised to cortisone by the action of 11β-hydroxysteroid dehydrogenase type 2, and cortisone is partly responsible for the variable interference observed in current salivary cortisol immunoassays. The aim of this study was to validate an assay for the simultaneous analysis of salivary cortisol and cortisone using the Spark Holland Symbiosis™ in eXtraction liquid chromatography-tandem mass spectrometry (XLC-MS/MS) mode for fully automated online solid phase extraction (SPE). Saliva samples were diluted in water with the addition of internal standard (d4-cortisol and d7-cortisone). Online SPE was performed using the Spark Holland Symbiosis™ with HySphere™ C18 SPE cartridges and compounds were eluted onto a Phenomenex® C18 guard column attached to a Phenomenex® Onyx monolithic C18 column for chromatography. Mass spectrometry used the Waters® Xevo™ TQ MS in electrospray positive mode. Cortisol and cortisone eluted with their internal standards at 1.95 and 2.17 min, respectively, with a total run time of four minutes. No evidence of ion-suppression was observed. The assay was linear up to 3393 nmol/L for cortisol and 3676 nmol/L for cortisone, with lower limits of quantitation of 0.75 nmol/L and 0.50 nmol/L, respectively. Intra- and inter-assay imprecision was cortisone across three levels of internal quality control, with accuracy and recovery within accepted limits. High specificity was demonstrated following interference studies which assessed 29 structurally-related steroids at supra-physiological concentrations. We have successfully validated an assay for the simultaneous analysis of salivary cortisol and cortisone using XLC-MS/MS and fully automated online SPE. The assay benefits from increased specificity compared to immunoassay and minimal sample preparation which allows high

  13. THE INHIBITION BY CORTISONE OF THE CYTOTOXIC ACTIVITY OF PPD ON TUBERCULIN-HYPERSENSITIVE CELLS IN TISSUE CULTURE

    Science.gov (United States)

    Leahy, Robert H.; Morgan, Herbert R.

    1952-01-01

    Using the roller tube method of tissue culture, it has been shown that cortisone and compound F inhibit the cytotoxic action of PPD upon macrophages from the splenic tissue of tuberculous guinea pigs. Pretreatment of the cells for 24 hours with hormones before exposure to PPD was found to be essential. Estrone and desoxycorticosterone glucoside had no protective activity. Certain advantages of the tissue culture method in studies of tuberculin hypersensitivity and possible mechanisms and implications of this protective action of cortisone are discussed. PMID:13022849

  14. [Simultaneous determination of adrenaline, noradrenaline, cortisone and cortisol in plasma with HPLC/MS/MS].

    Science.gov (United States)

    Yong, Li; Wang, Yu; Zou, Xiao-Li; Zhu, Lan; Xie, Hui-Ru; Li, Long-Jiang

    2014-01-01

    To develop a method for simultaneous determination of adrenaline, noradrenaline, cortisone and cortisol in plasma using HPLC/MS/MS. Sample proteins were precipitated with acetonitrile and the sample solution was injected into HPLC/MS/MS after centrifugation at 15,000 r/min for 5 min. Electrospray ionization (ESI) and the positive ion detection were applied with a multiple reaction monitoring (MRM) mode for quantitative analyses. Under the optimal conditions, good linearity (r > 0.999) was observed in the range of 0.02-200.00 ng/mL of target compounds. The detection limit reached 4.13 pg/mL, 4.64 pg/mL, 4.29 pg/mL and 4.52 pg/mL for adrenaline, noradrenaline, cortisone and cortisol respectively. The inter-day and intra-day precisions ranged from 1.19%-5.42% and 2.16%-6.04% respectively. Satisfied results were achieved using human plasma samples, with a spiked recovery in the range of 80.0%-109.0% and a relative standard deviation of 3.93%-7.57%. The proposed method is quick, sensitive and suitable for batch analyses of plasma samples.

  15. One-year MR imaging follow-up of patients with multiple sclerosis under cortisone therapy

    Energy Technology Data Exchange (ETDEWEB)

    Uhlenbrock, D.; Herbe, E.; Seidel, D.; Gehlen, W.

    1989-03-01

    Twenty patients with relapsing/remitting course of MS were studied four times with MR imaging over the course of one year. First MR was undertaken during the acute relapse, afterwards patients were given cortisone therapy for four to six weeks. The second MR study followed 4-6 weeks after the first, the patients at this time being in remission. The third MR study was carried out 4 months after the first, the last scan one year after the first. The total number of lesions varied, though not greatly, over the whole follow-up, but there was an influence of the clinical course of MS on the pattern of lesions in MR imaging, mostly in respect to the number of confluences and the size of the lesions. Follow-up over one year showed that the inflammatory process produced an increase in the number of plaques, independent of the fact that most patients stayed in remission. A delayed effect of the cortisone therapy on the size, number, and confluence of plaques is suggested whilst clinical signs improved in most cases immediately after the beginning of drug therapy. Independent of the clinical course of the disease in some cases plaques previously seen vanished and others appeared in one and the same examination.

  16. Multi-matrix assay of cortisol, cortisone and corticosterone using a combined MEPS-HPLC procedure.

    Science.gov (United States)

    Saracino, Maria A; Iacono, Corrado; Somaini, Lorenzo; Gerra, Gilberto; Ghedini, Nadia; Raggi, Maria A

    2014-01-01

    The development and validation of a bioanalytical assay for the simultaneous determination of cortisol, cortisone and corticosterone levels in several matrices, such as saliva, plasma, blood and urine samples have been described. The method is based on a rapid test which combines a microextraction by packed sorbent procedure and liquid chromatography-diode array technique. Chromatographic separation of the analytes (cortisol, cortisone and corticosterone) and the internal standard (methylprednisolone) was achieved in less than 10min on a reversed-phase pentafluorophenyl column using a mobile phase composed of phosphate buffer and acetonitrile. The assay was performed after an innovative microextraction procedure by means of C8 sorbent which guaranteed good clean-up of the matrices and satisfactory extraction yield of the analytes. Moreover, the method gave linear results over a range of 5-100ngmL(-1) and showed good selectivity and precision. This method was successfully applied for quantifying corticosteroids in specific matrices derived from some healthy volunteers in comparison to two socially diversified groups, namely former heroin addicts undergoing opioid replacement therapy and poly-drug abusers. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. Plasma cortisol and cortisone in pregnancies with normal and anencephalic fetuses.

    Science.gov (United States)

    Fencl, M D; Osathanondh, R; Tulchinsky, D

    1976-07-01

    Plasma cortisol (F), cortisone (E), and progesterone (P), were measured in the umbilical vein (UV), umiblical artery (UA), and maternal peripheral vein (MPV) of 17 normal patients, and of 8 patients carying anencephalic fetuses. The plasma F in MPV of patients undergoing vaginal delivery after labor of spontaneous onset was significantly higher than that of patients delivered by elective cesarean section, whereas the plasma F concentrations in the UA or UV of the 2 groups were not statistically different from each other. The anencephalic fetuses had UA plasma F and E concentrations which were significantly lower than those of normal fetuses, suggesting that a main portion of UA cortisol and cortisone originates in the fetal adrenal. The UV and MPV plasma F and E concentrations of patients carrying anencephalic fetuses did not differ, however, from those of normal patients, suggesting that these UV corticoids are derived mainly from maternal sources. The amniotic fluid cortisol levels of the patients carying anencephalic fetuses were lower than those observed in the normal pregnancies, suggesting that amniotic fluid cortisol is derived mainly from fetal sources.

  18. Effects of cortisone acetate, methylprednisolone and medroxyprogesterone on wound contracture and epithelization in rabbits.

    Science.gov (United States)

    Lenco, W; Mcknight, M; Macdonald, A S

    1975-01-01

    Standardized flank wounds were made on 20 rabbits divided into the following five groups: Group 1 served as controls, Group 2 were given cortisone acetate 6.25 mg/kg/day (I.M.), Group 3--methylprednisolone (Solu-Medrol) 1 mg/kg/day, Group 4--medroxyprogesterone (Depo-Provera) 35 mg/kg/day, Group 5--methylprednisolone 1 mg/kg/day and medroxyprogresterone 35 mg/kg/day. Wound contracture and epithelization was measured by planimetry of photographs taken twice weekly; weekly weights were recorded, and the maturation phase of wound healing followed in the control and methylprednisolone groups. All three steroids prolonged the latent phase of wound healing, slowed the rate and decreased the total amount of contracture. Cortisone showed the most inhibition of wound contracture and was the only steroid to inhibit epithelization suggesting it may have a slightly different or more potent mode of action. When the methylprednisolone group was followed for seven weeks on daily injections, the maturation phase of wound healing was inhibited, and this inhibition persisted during the next nine weeks after the drug was withdrawn. Only the control and the medroxyprogesterone group gained weight. Combining medroxyprogesterona and methylprednisolone resulted in the severest weight loss of 20% with a 60% mortality. PMID:1119869

  19. Dry Needling Versus Cortisone Injection in the Treatment of Greater Trochanteric Pain Syndrome: A Noninferiority Randomized Clinical Trial.

    Science.gov (United States)

    Brennan, Kindyle L; Allen, Bryce C; Maldonado, Yolanda Munoz

    2017-04-01

    Study Design Prospective, randomized, partially blinded. Background Greater trochanteric pain syndrome (GTPS) is the current terminology for what was once called greater trochanteric or subgluteal bursitis. Cortisone (corticosteroid) injection into the lateral hip has traditionally been the accepted treatment for this condition; however, the effectiveness of injecting the bursa with steroids is increasingly being questioned. An equally effective treatment with fewer adverse side effects would be beneficial. Objective To investigate whether administration of dry needling (DN) is noninferior to cortisone injection in reducing lateral hip pain and improving function in patients with GTPS. Methods Forty-three participants (50 hips observed), all with GTPS, were randomly assigned to a group receiving cortisone injection or DN. Treatments were administered over 6 weeks, and clinical outcomes were collected at baseline and at 1, 3, and 6 weeks. The primary outcome measure was the numeric pain-rating scale (0-10). The secondary outcome measure was the Patient-Specific Functional Scale (0-10). Medication intake for pain was collected as a tertiary outcome. Results Baseline characteristics were similar between groups. A noninferiority test for a repeated-measures design for pain and averaged function scores at 6 weeks (with a noninferiority margin of 1.5 for both outcomes) indicated noninferiority of DN versus cortisone injection (both, PTherapy, level 1b. Registered December 2, 2015 at www.clinicaltrials.gov (NCT02639039). J Orthop Sports Phys Ther 2017;47(4):232-239. Epub 3 Mar 2017. doi:10.2519/jospt.2017.6994.

  20. Salivary Cortisol and Cortisone do not Appear to be Useful Biomarkers for Monitoring Hydrocortisone Replacement in Addison's Disease.

    Science.gov (United States)

    Ross, I L; Lacerda, M; Pillay, T S; Blom, D J; Johannsson, G; Dave, J A; Levitt, N S; Haarburger, D; van der Walt, J-S

    2016-12-01

    Salivary cortisol has been used to monitor hydrocortisone replacement in patients with Addison's disease (AD). Since salivary cortisol is metabolised to salivary cortisone, it may be an adjunctive analyte to assess adequacy of hydrocortisone replacement in patients with AD. We aimed to characterise the exposure of salivary cortisol and cortisone in patients and healthy controls. We measured salivary cortisol and cortisone by liquid chromatography-tandem mass spectrometry and constructed a day curve (08:00 until 24:00 h) with 16 time points in 25 AD patients taking their usual hydrocortisone dose and in 26 healthy controls. The median (interquartile range) area under the curve (AUC) for cortisol was not different for patients, compared with controls [55.63 (32.91-151.07) nmol*min*l(-1) vs. 37.49 (27.41-52.00) nmol*min*l(-1); p=0.098, respectively], whereas the peak cortisol Cmax was higher in patients [32.61 (5.75-146.19) nmol/l vs. 8.96 (6.96-12.23) nmol/l; p=0.013], compared with controls. The AUC for cortisone [23.65 (6.10-54.76) nmol*min*l(-1) vs. 227.73 (200.10-280.52) nmol*min*l(-1); p≤ 0.001, respectively], and peak cortisone Cmax was lower in patients than in controls [11.11 (2.91-35.85) nmol/l vs. 33.12 (25.97-39.95) nmol/l; p=0.002]. The AUC for salivary cortisol and salivary cortisone were not correlated with any measures of hydrocortisone dose. The time-course and AUC of salivary cortisol were similar between Addison's patients and healthy controls. Patients had substantially lower salivary cortisone AUC, compared to healthy controls. Salivary cortisol AUC and pharmacokinetics were not related to hydrocortisone dose and thus are not likely useful markers for the adequacy of hydrocortisone replacement. © Georg Thieme Verlag KG Stuttgart · New York.

  1. Investigation on possible transformations of cortisol, cortisone and cortisol glucuronide in bovine faecal matter using liquid chromatography-mass spectrometry.

    Science.gov (United States)

    Arioli, Francesco; Fidani, Marco; Casati, Alessio; Fracchiolla, Maria L; Pompa, Giuseppe

    2010-04-01

    Given the close resemblance of the ring A structure of prednisolone and prednisone on the one hand, and of androstadienedione on the other, the transformation of cortisol and cortisone into prednisolone and prednisone in cattle faeces was evaluated. A simple method that does not involve extraction but only the 1:100 dilution of cattle faeces, spiking with 400ng/mL cortisol, cortisone or cortisol glucuronide and incubation of the suspension, was used. The analyses were performed by HPLC-MS(3) to detect the supposed Delta(1) dehydrogenation of the glucocorticoids. The decision limits (CCalpha) and detection capabilities (CCbeta) were 2.0 and 3.0ng/mL for cortisol, cortisone and prednisolone, 3.0 and 4.0ng/mL for cortisol glucuronide and 7.0 and 10.0ng/mL for prednisone, respectively. Intra-day and inter-day coefficients of variation (CV%), were 5.6-6.2 and 5.2-6.6 for cortisol glucuronide, cortisol, cortisone and prednisolone, and 16.0 and 16.2 for prednisone, respectively. The recoveries were in the range 110-143% for all analytes. Regression coefficients (R2) were in the range 0.996-0.999 for all analytes. The results show the hydrolysis of the conjugated form and the dehydrogenation in ring A in diluted faeces. It is therefore predicted that urine contaminated with faeces may be positive for prednisone and prednisolone in the same way as they are positive for boldenone, i.e. as a result of microbiological dehydrogenase activity on cortisol and cortisone.

  2. Biomedical Evaluation of Cortisol, Cortisone, and Corticosterone along with Testosterone and Epitestosterone Applying Micellar Electrokinetic Chromatography

    Science.gov (United States)

    Bączek, Tomasz; Olędzka, Ilona; Konieczna, Lucyna; Kowalski, Piotr; Plenis, Alina

    2012-01-01

    The validated micellar electrokinetic chromatography (MEKC) was proposed for the determination of five steroid hormones in human urine samples. That technique allowed for the separation and quantification of cortisol, cortisone, corticosterone, testosterone, and epitestosterone and was sensitive enough to detect low concentrations of these searched steroids in urine samples at the range of 2–300 ng/mL. The proposed MEKC technique with solid-phase extraction (SPE) procedure was simple, rapid, and has been successfully applied as a routine procedure to analyze steroids in human urine samples. The MEKC method offered a potential in clinical routine practice because of the short analysis time (8 min), low costs, and simultaneous analysis of five endogenous hormones. Due to its simplicity, speed, accuracy, and high recovery, the proposed method could offer a tool to determine steroid hormones as potential biomarkers in biomedical investigations, what was additionally revealed with healthy volunteers. PMID:22536129

  3. Some social aspects of discovery, synthesis and production of cortisone in the 1930s-1950s.

    Science.gov (United States)

    Jadreškić, Daria

    2016-12-01

    A discovery, synthesis and therapeutic application of cortisone present a paradigm for modern translational medicine (Hillier 2007, Saenger 2010), since they represented a joint achievement of discoveries by biochemists, Edward Calvin Kendall and Tadeus Reichstein; large scale synthesis by an industrial chemist, Lewis Hastings Sarett, and therapeutic application by a rheumatologist, Philip Showalter Hench. The goal of translational medicine is to speed up the process between basic research and clinical practice, and to integrate multiple disciplines in order to understand diverse outcomes (Zhang et al. 2014). In this paper conditions that made this basic/applied/clinical research interface possible will be presented: the rise of steroid chemistry, simultaneous individual accomplishments as well as continuous cooperation among scientists, military competitiveness, and cooperation among pharmaceutical companies.

  4. Cross-polarization/magic-angle spinning NMR studies of polymorphism: Cortisone acetate

    Science.gov (United States)

    Harris, Robin K.; Kenwright, Alan M.; Say, Barry J.; Yeung, Race R.; Fletton, Richard A.; Lancaster, Robert W.; Hardgrove, George L.

    13C CPMAS spectra have been recorded for nine samples of cortisone acetate (21-acetoxy-17α-hydroxy-4-pregnene-3,11,20-trione, C 23H 30O 6) and the observed resonances are attributed to six crystalline forms. Two of these forms are novel. The spectra of all six are entirely distinct. The resonances are assigned to individual carbon atoms on the basis of previously-determined solution-state spectra together with dipolar dephasing experiments and observations of shielding anisotropies as reflected in spinning sideband manifolds. The results are interpreted in relation to known crystal structures. The value of solid-state NMR for analysis of polymorph mixtures is emphasized.

  5. Ear Keloid Treated with Infiltrated Non-cross-linked Hyaluronic Acid and Cortisone Therapy.

    Science.gov (United States)

    DI Stadio, Arianna

    Several treatments are available to treat the keloid scar. Keloids have the tendency to recur after surgical removal and new treatments for keloid scars include radiotherapy, cryotherapy or compressive therapy. Topical treatments have been also used to treat this pathology, such as injections or medical device applications. A 33-year-old man came to our attention and we treated him for a keloid scar located between the ear's helical tubercle and the ante-helix upper root of the left ear. This keloid arose 20 years earlier following a bilateral otoplasty. We proposed an association therapy using a non-cross-linked hyaluronic acid and cortisone. The associated treatment was able to determine a complete resolution of the keloid without recurrence several months later. Copyright © 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  6. Biomedical Evaluation of Cortisol, Cortisone, and Corticosterone along with Testosterone and Epitestosterone Applying Micellar Electrokinetic Chromatography

    Directory of Open Access Journals (Sweden)

    Tomasz Bączek

    2012-01-01

    Full Text Available The validated micellar electrokinetic chromatography (MEKC was proposed for the determination of five steroid hormones in human urine samples. That technique allowed for the separation and quantification of cortisol, cortisone, corticosterone, testosterone, and epitestosterone and was sensitive enough to detect low concentrations of these searched steroids in urine samples at the range of 2–300 ng/mL. The proposed MEKC technique with solid-phase extraction (SPE procedure was simple, rapid, and has been successfully applied as a routine procedure to analyze steroids in human urine samples. The MEKC method offered a potential in clinical routine practice because of the short analysis time (8 min, low costs, and simultaneous analysis of five endogenous hormones. Due to its simplicity, speed, accuracy, and high recovery, the proposed method could offer a tool to determine steroid hormones as potential biomarkers in biomedical investigations, what was additionally revealed with healthy volunteers.

  7. Growth hormone, insulin-like growth factor-I and the cortisol-cortisone shuttle.

    Science.gov (United States)

    Stewart, P M; Toogood, A A; Tomlinson, J W

    2001-01-01

    In peripheral tissues, corticosteroid hormone action is determined, in part, through the activity of 11beta-hydroxysteroid dehydrogenases (11beta-HSD), two isozymes of which interconvert hormonally active cortisol (F) and inactive cortisone (E). 11beta-HSD type 2 (11beta-HSD2) inactivates F to E in the kidney, whilst 11beta-HSD type 1 (11beta-HSD1) principally performs the reverse reaction activating F from E in the liver and adipose tissue. Alteration in expression of these 11beta-HSD isozymes in peripheral tissues modifies corticosteroid action: loss of 11beta-HSD2 activity in the kidney results in cortisol-induced mineralocorticoid excess, and loss of hepatic 11beta-HSD1 activity improves insulin sensitivity through a reduction in cortisol-induced gluconeogenesis and hepatic glucose output. Conversely, overexpression of 11beta-HSD1 in omental adipose tissue can stimulate glucocorticoid-induced adipocyte differentiation which may lead to central obesity. Patients with hypopituitarism have many clinical features in common with patients with Cushing's syndrome--notably visceral obesity, insulin resistance, osteoporosis and increased vascular mortality. Our hypothesis was that many of these features may be explained by an effect of growth hormone (GH) on the 11beta-HSD isozymes. As assessed by urinary free cortisol/urinary free cortisone ratios and endorsed through in vitro studies, neither GH nor insulin-like growth factor (IGF)-I affect 11beta-HSD2 activity. Patients with acromegaly show a reduction in hepatic-derived metabolites of cortisol/cortisone - levels return to normal when GH concentrations are normalized. Conversely, patients with GH deficiency in the setting of hypopituitarism demonstrate an increased cortisol/cortisone metabolite ratio and reduction in circulating cortisol concentrations in patients on hydrocortisone replacement. Treatment with low-dose GH replacement reverses these abnormalities. These clinical data suggest that GH (and/or IGF

  8. High cortisol and cortisone levels are associated with breast milk dioxin concentrations in Vietnamese women.

    Science.gov (United States)

    Kido, Teruhiko; Dao, Tung Van; Ho, Manh Dung; Duc Dang, Nhu; Pham, Ngoc Thien; Okamoto, Rie; Pham, Tai The; Maruzeni, Shoko; Nishijo, Muneko; Nakagawa, Hidewaki; Honma, Seijiro; Le, Son Ke; Nguyen, Hung Ngoc

    2014-01-01

    Dioxin (polychlorinated dibenzodioxins+polychlorinated dibenzofurans) is one of the most toxic chemical substances known. Although it is suspected to cause endocrine disruption, very few epidemiological studies have been carried out on its effects on human steroid hormones. The aim of this study was to elucidate the association of dioxin exposure with steroid hormone levels in the saliva and serum of Vietnamese women. Two areas, namely Phu Cat (hot spot) and Kim Bang (nonexposed area), were selected for the study. The study subjects consisted of 51 and 58 women respectively. Saliva, blood, and breast milk samples were collected from the subjects in both the areas. Cortisol, cortisone, DHEA, androstenedione, estrone, and estradiol levels in serum and saliva were determined by liquid chromatography-tandem mass spectrometry; dioxin concentrations in breast milk were measured by gas chromatography-mass spectrometry. Dioxin concentrations in the breast milk of women from the dioxin hot spot were three to four times higher than those in the breast milk of women from the nonexposed area. Good correlations were found between the levels of six steroid hormones in saliva and those in serum respectively. Salivary and serum cortisol and cortisone levels in women from the dioxin hot spot were significantly higher than those in women from the nonexposed area (P<0.001) and those in all the subjects were positively associated with dioxin concentrations in Vietnamese women (P<0.01). These results suggest that dioxin influences steroidogenesis in humans. Saliva samples can be used for hormone analysis and are therefore excellent specimens in epidemiological studies.

  9. The Effect of Glycyrrhetinic Acid on Pharmacokinetics of Cortisone and Its Metabolite Cortisol in Rats

    Directory of Open Access Journals (Sweden)

    Dan Lin

    2012-01-01

    Full Text Available The purpose of this paper is to study pharmacokinetics of cortisone (E and its metabolite cortisol (F in rats after administration of glycyrrhetinic acid (GA and cortisone. Healthy male SD rats were randomized to be given 20 mg/kg E or E combined with 10 mg/kg GA. Blood samples were collected at 5, 10, 20, 40, 60, 90, 120, 150, 180, and 240 min after administration. The serum concentrations of E and F were determined by HLPC and pharmacokinetic parameters were calculated using DASver2.0 software. The parameters of AUC(0−t, AUC(0−∞, and Cmax for E in the group of E + GA were significantly higher than those in the group of E (P<0.01; the half-time (t1/2β was extended compared to E (P<0.05 and CL/F was dropped obviously (P<0.01. The rise in AUC(0−t, AUC(0−∞, and Cmax for cortisol in the group of E + GA was significantly compared to the group of E (P<0.01. CL/F was lower than E (P<0.01 and the half-time (t1/2β was slightly extended. In this study, we find that GA restrains the metabolism of E and F and thus increases AUC, t1/2β, and Cmax of E and F, which may be related to its inhibition effect on 11β-hydroxysteroid dehydrogenase (11β-HSD.

  10. Pathogenicity of Candida viswanathii for normal and cortisone-treated mice.

    Science.gov (United States)

    Randhawa, H S; Mishra, S K; Damodaran, V N; Prakash, A; Chowdhary, A; Khan, Z U

    2015-12-01

    The pathogenicity of Candida viswanathii, PCI 501/1 (CBS 4024), originally isolated from CSF of a fatal case of meningitis in India, is reported. Also, included is a global overview of the occurrence of C. viswanathii in clinical and environmental sources. The investigation was done in normal and cortisone-treated albino mice challenged intravenously with variable doses of 1×10(6), 4×10(6) and 16×10(6) actively growing yeast cells of the fungus. The animals were kept under observation up to 3 weeks when they were sacrificed for a mycological and histopathologic study. As apparent from the data on morbidity and mortality, the species exhibited low virulence for normal mice, whereas it caused significantly higher mortality (Pcortisone group. Likewise, there was overall higher recovery of C. viswanathii in culture from the cortisone-treated than in the normal group of mice. These observations are indicative of C. viswanathii being an opportunistic pathogen. It is recognized that a definitive identification of C. viswanathii requires mycological expertise for comprehensive phenotypic characterization or the application of expensive techniques such as Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-TOF MS) and molecular techniques, facilities for which are generally lacking in a vast majority of laboratory diagnostic centers especially in developing countries. Consequently, the prevalence of C. viswanathii in clinical and environmental samples is currently likely to be underestimated. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  11. The effect of glycyrrhetinic acid on pharmacokinetics of cortisone and its metabolite cortisol in rats.

    Science.gov (United States)

    Lin, Dan; Sun, Wei; Wang, Zhe; Chen, Lian-Guo; Chen, Xiao-Le; Wang, Shuang-Hu; Li, Wan-Shu; Ge, Ren-Shan; Hu, Guo-Xin

    2012-01-01

    The purpose of this paper is to study pharmacokinetics of cortisone (E) and its metabolite cortisol (F) in rats after administration of glycyrrhetinic acid (GA) and cortisone. Healthy male SD rats were randomized to be given 20 mg/kg E or E combined with 10 mg/kg GA. Blood samples were collected at 5, 10, 20, 40, 60, 90, 120, 150, 180, and 240 min after administration. The serum concentrations of E and F were determined by HLPC and pharmacokinetic parameters were calculated using DASver2.0 software. The parameters of AUC((0-t)), AUC((0-∞)), and C(max) for E in the group of E + GA were significantly higher than those in the group of E (P < 0.01); the half-time (t(1/2β)) was extended compared to E (P < 0.05) and CL/F was dropped obviously (P < 0.01). The rise in AUC((0-t)), AUC((0-∞)), and C(max) for cortisol in the group of E + GA was significantly compared to the group of E (P < 0.01). CL/F was lower than E (P < 0.01) and the half-time (t(1/2β)) was slightly extended. In this study, we find that GA restrains the metabolism of E and F and thus increases AUC, t(1/2β), and C(max) of E and F, which may be related to its inhibition effect on 11β-hydroxysteroid dehydrogenase (11β-HSD).

  12. Depot-specific Regulation of the Conversion of Cortisone to Cortisol in Human Adipose Tissue

    Science.gov (United States)

    Lee, Mi-Jeong; Fried, Susan K.; Mundt, Steven S.; Wang, Yanxin; Sullivan, Sean; Stefanni, Alice; Daugherty, Bruce L.; Hermanowski-Vosatka, Anne

    2015-01-01

    Objective Our main objective was to compare the regulation of cortisol production within omental (Om) and abdominal subcutaneous (Abd sc) human adipose tissue. Methods and Procedures Om and Abd sc adipose tissue were obtained at surgery from subjects with a wide range of BMI. Hydroxysteroid dehydrogenase (HSD) activity (3H-cortisone and 3H-cortisol interconversion) and expression were measured before and after organ culture with insulin and/or dexamethasone. Results Type 1 HSD (HSD1) mRNA and reductase activity were mainly expressed within adipocytes and tightly correlated with adipocyte size within both depots. There was no depot difference in HSD1 expression or reductase activity, while cortisol inactivation and HSD2 mRNA expression (expressed in stromal cells) were higher in Om suggesting higher cortisol turnover in this depot. Culture with insulin decreased HSD reductase activity in both depots. Culture with dexamethasone plus insulin compared to insulin alone increased HSD reductase activity only in the Om depot. This depot-specific increase in reductase activity could not be explained by an alteration in HSD1 mRNA or protein, which was paradoxically decreased. However, in Om only, hexose-6-phosphate dehydrogenase (H6PDH) mRNA levels were increased by culture with dexamethasone plus insulin compared to insulin alone, suggesting that higher nicotinamide adenine dinucleotide phosphate-oxidase (NADPH) production within the endoplasmic reticulum (ER) contributed to the higher HSD reductase activity. Discussion We conclude that in the presence of insulin, glucocorticoids cause a depot-specific increase in the activation of cortisone within Om adipose tissue, and that this mechanism may contribute to adipocyte hypertrophy and visceral obesity. PMID:18388900

  13. Diagnostic accuracy of increased urinary cortisol/cortisone ratio to differentiate ACTH-dependent Cushing's syndrome.

    Science.gov (United States)

    Ceccato, Filippo; Trementino, Laura; Barbot, Mattia; Antonelli, Giorgia; Plebani, Mario; Denaro, Luca; Regazzo, Daniela; Rea, Federico; Frigo, Anna Chiara; Concettoni, Carolina; Boscaro, Marco; Arnaldi, Giorgio; Scaroni, Carla

    2017-06-07

    Differential diagnosis between Cushing's Disease (CD) and Ectopic ACTH Syndrome (EAS) may be a pitfall for endocrinologists. The increasing use in clinical practice of chromatography and mass spectrometry improves the measurement of urinary free cortisol (UFF) and cortisone (UFE). We have recently observed that cortisol to cortisone ratio (FEr) was higher in a small series of EAS; in this study we collected a larger number of ACTH-dependent Cushing's Syndrome (CS) to study the role of FEr to characterize the source of corticotropin secretion. High-pressure liquid chromatography with UV detection (HPLC-UV, n=35) or liquid chromatography-tandem mass spectrometry (LC-MS/MS, n=72) were used to measure UFF, UFE and FEr in 83 patients with CD and 24 with EAS. UFF, UFE and FEr levels were higher in EAS than in CD (UFF: 6671 vs 549 nmol/24 hours; UFE: 2069 vs 464 nmol/24 hours; FEr: 4.13 vs 0.97; all P1.15 (the best ROC-based threshold) was able to distinguish CD from EAS with 75% sensitivity (SE) and 75% specificity (SP), AUC 0.811; results were similar between HPLC-UV (SE 73%, SP 79%, AUC 0.708) and LC-MS/MS (SE 77%, SP 73%, AUC 0.834; P=.727). The diagnostic accuracy of FEr was similar to that of CRH test or high-dose dexamethasone suppression test (respectively P=.171 and P=.683), also combined. Finally, FEr was able to increase the number of correct diagnosis in patients with discordant dynamic tests. Urinary FEr >1.15 was able to suggest EAS, with a diagnostic accuracy similar to that of other dynamic tests proposed to study ACTH-dependent CS. © 2017 John Wiley & Sons Ltd.

  14. Method development for cortisol and cortisone by micellar liquid chromatography using sodium dodecyl sulphate: application to urine samples of rugby players.

    Science.gov (United States)

    Izquierdo-Hornillos, R; Gonzalo-Lumbreras, R; Santos-Montes, A

    2005-01-01

    The chromatographic behavior of cortisol and cortisone using a micellar medium of sodium dodecyl sulphate (SDS) as surfactant, a Hypersil C18 (150- x 3.2-mm i.d., 5 microm) column, a flow rate of 0.5 mL/min, and UV absorbance detection at 245 nm is described. The effect of several organic modifiers and the surfactant concentration on the separation is studied. A mobile phase of 18 mM SDS and 8.3% tetrahydrofuran allows for the separation of cortisol and cortisone up to baseline. These results are also achieved by applying a bivariant optimization method. The proposed method is sensitive, reproducible, and selective. In addition, it is less expensive than conventional high-performance liquid chromatography methods for cortisol and cortisone. The method is applied to the determination of cortisol and cortisone in urine samples of rugby players before and after stress for doping control purposes.

  15. Evaluation of hepatic 11 beta-hydroxysteroid dehydrogenase activity by cortisone acetate test in young adults with diabetes mellitus type 1.

    Science.gov (United States)

    Šimůnková, K; Hampl, R; Hill, M; Kříž, L; Vrbíková, J; Kvasničková, H; Vondra, K

    2011-01-01

    Cortisone acetate test was performed in twelve young adult patients with diabetes mellitus type 1, after dexamethasone administration to suppress endogenous cortisol production. Previous screening revealed that all of the subjects had peak cortisol responses in the range from subnormal to normal, as determined by a low-dose Synacthen test. The aim was to find out whether these patients would exhibit different conversion of cortisone to cortisol by 11beta-hydroxysteroid dehydrogenase. Using multifactorial ANOVA the following significant relationships were obtained between cortisol or cortisol/cortisone ratio measured during the test and other parameters examined a) before dexamethasone suppression and b) during the test: a) Cortisol at 120(th) minute negatively correlated with daily insulin dose and positively with basal aldosterone. Cortisol/cortisone ratio at 60(th), 120(th), 180(th), and 240(th) minute negatively correlated with basal aldosterone/plasma renin activity ratio, urinary free cortisol/24 hours and positively with basal dehydroepindrosterone sulphate. b) Cortisol at 120(th) minute negatively correlated with suppressed basal serum glycemia; cortisol/cortisone ratio during the whole test negatively correlated with supressed basal ACTH. The examination of peripheral metabolism of cortisol using cortisone acetate test in patients with diabetes mellitus type 1 showed adaptive changes of 11beta-hydroxysteroid dehydrogenace activity associated with altered cortisol tissue supply.

  16. Steroid hormone "cortisone" and "20-hydroxyecdysone" involved in the non-specific immune responses of white shrimp (Litopenaeus vannamei).

    Science.gov (United States)

    Wu, Yu-Sheng; Chang, Ching-Hsu; Nan, Fan-Hua

    2016-09-01

    This study investigated the effect of two steroid hormones on phenoloxidase activity, O2(-) production in the haemocytes, total haemocyte count (THC), superoxide dismutase (SOD) activity, glutamate oxaloacetate transaminase (GOT) activity, glutamate pyruvate transaminase (GPT) activity, and plasma cholesterol concentrations in white shrimps (Litopenaeus vannamei). Phenoloxidase activity, THC and plasma cholesterol concentration in shrimps treated with cortisone and 20-hydroxyecdysone were found to be lower when compared with the control groups. In the observation of O2(-) production, treatment of cortisone and hydroxyecdysone were reducing the activity in the 1st day, but to be undiversified with the elapsed time. By contrast, SOD activity in the hepatopancreas, plasma GOT activity, and GPT activity were significantly increased when compared with the control groups. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. [Management of Idiopathic Frozen Shoulder - Prospective Evaluation of Mobilisation under Anaesthesia and an Additional Subacromial Cortisone Injection].

    Science.gov (United States)

    Meyer, C; Stein, G; Kellinghaus, J; Schneider, T L

    2015-12-01

    Management of primary frozen shoulder is still controversial. Many authors tend to treat patients with an arthroscopic release, if conservative therapy fails. We aimed to demonstrate the efficiency of manipulation under anaesthesia (MUA) in patients with primary frozen shoulder and to contrast the outcome of single MUA with the results of MUA with an additional subacromial injection of cortisone. A prospective trial with a 1-year follow-up was performed. Between 2008 and 2011 30 patients with idiopathic frozen shoulder underwent MUA, 15 of them received an additional injection of triamcinolone and bupivacain. Thereafter all patients underwent a standardised physiotherapy treatment regime for three months. The patients were assessed for pain, function, range of motion and the Constant-Murley score (CMS) before MUA as well as 1, 6 and 12 months after the intervention. Range of motion increased significantly (p cortisone however does not generate a significant improvement. Georg Thieme Verlag KG Stuttgart · New York.

  18. Limited therapeutic benefits of intra-articular cortisone injection for patients with femoro-acetabular impingement and labral tear.

    Science.gov (United States)

    Krych, Aaron J; Griffith, Timothy B; Hudgens, Joshua L; Kuzma, Scott A; Sierra, Rafael J; Levy, Bruce A

    2014-04-01

    Intra-articular (IA) hip cortisone injection is commonly performed as a therapeutic modality in patients with femoral acetabular impingement (FAI). To our knowledge, there is no published data evaluating the clinical benefit of these injections. The purpose of this study was to assess the efficacy of therapeutic IA cortisone injection in these patients. At our institution, patients with FAI and labral tear prospectively recorded their numerical rating scale (NRS) pain scores pre-injection, during post-injection anaesthetic phase, and at 14 days post-injection. From this cohort, all patients treated with guided IA cortisone injection, no radiographic evidence of arthritis (Tönnis grade 0 or 1) and pain relief during the anaesthetic phase of the IA injection were included. An absolute change of two points on the NRS score was considered the minimal amount of clinically significant pain relief. Pain scores were compared between the different types of steroid injected. Fifty-four patients (35 females, 19 males) with a mean age of 32 ± 12 years were included. Average median pre-injection NRS score was 7.0 (range 2.5-10.0), post-injection anaesthetic phase was 1.0 (range 0.0-5.0), and 14 day post-injection was 5.0 (range 0.0-10.0). As a group, NRS scores significantly diminished from post-injection anaesthetic phase to 14 days post-injection (p cortisone injection has limited clinical benefit as a therapeutic modality. However, anaesthetic-only IA injections for patients who may be candidates for hip arthroscopy can be a useful diagnostic tool.

  19. Immunoreactive cortisone in droppings reflect stress levels, diet and growth rate of gull-billed tern chicks.

    Science.gov (United States)

    Albano, Noelia; Santiago-Quesada, Francisco; Masero, José A; Sánchez-Guzmán, Juan M; Möstl, Erich

    2015-03-01

    Blood levels of corticosterone have been traditionally analyzed to assess stress levels in birds; however, measuring steroid hormone metabolites in feces and droppings has gained much interest as a noninvasive technique successfully used for such purposed in vertebrates. Diet may affect these fecal metabolite levels (e.g., due to nutritional stress), however, this variable has not been taken into account in studies with chicks despite the great dietary flexibility of many avian species. In this study, we addressed for the first time this key issue and validated the technique in wild gull-billed tern chicks (Gelochelidon nilotica). Several enzyme immunoassays were used to determine the most appropriate test to measure the stress response. Subsequently, we performed an experiment in captivity to assess adrenocortical activity in gull-billed tern chicks fed with two diets: piscivorous vs. insectivorous. Finally, the relation between the chicks' growth rate and excreted immunoreactive glucocorticoid metabolites (EGMs) was also evaluated. We found the immunoreactive cortisone metabolites to be a good index of stress (as being an index of adrenocortical reactivity) in chicks of this species. Fish-fed chicks had higher levels of cortisone metabolites when comparing both concentration and total daily excreted metabolites. Within each treatment diet, cortisone metabolite levels and growth rates were negatively correlated. These findings suggest that the diet should be considered when using this technique for comparative purposes and highlight the trade-off between stress levels and chicks growth rates. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Study on dissolution mechanism of cortisol and cortisone from hair matrix with liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Xing, Xue; Chen, Zheng; Li, Jifeng; Zhang, Jing; Deng, Huihua; Lu, Zuhong

    2013-06-05

    Hair cortisol has been used as a biomarker of chronic stress. The detected contents of hair cortisol might depend on the incubation duration in solvents for no-milled hair samples with 3-layer structure. However, there was no research on the dissolution mechanism of hair analytes. After uniform mixture, no-milled hair samples were incubated in methanol and water for the 12 different durations and milled hair was done as comparison. Hair cortisol and cortisone were determined with high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). The measured concentrations of hair cortisol and cortisone showed ≥2 maxima during the entire incubation in methanol and water from 5 min to 72 h for no-milled hair. Hair cortisol concentration measured by LC-MS/MS was increased with the incubation duration. Conversely, it was not held when hair was powdered prior to the incubation in methanol. Hair cortisol and cortisone were dissolved from hair matrix through the 2-stage or multistage mechanism, which might depend on the hair 3-layer structure and its degree of damage. Copyright © 2013 Elsevier B.V. All rights reserved.

  1. Gastrointestinal bleeding after high intake of omega-3 fatty acids, cortisone and antibiotic therapy: a case study.

    Science.gov (United States)

    Detopoulou, Paraskevi; Papamikos, Vasilios

    2014-06-01

    Omega-3 fatty acids exert a plethora of physiological actions including triglycerides lowering, reduction of inflammatory indices, immunomodulation, anti- thrombotic effects and possibly promotion of exercise performance. Their use is widespread and for commonly ingested doses their side- effects are minimal. We report a case of a 60 y amateur athlete who consumed about 20 g omega-3 fatty acids daily from supplements and natural sources for a year. After the intake of cortisone and antibiotics he presented duodenum ulcer and bleeding although he had no previous history of gastrointestinal problems. Although several animal data support gastro-protective effects of omega-3 fatty acids in the present case they were not able to prevent ulcer generation. The present observation may be explained by (i) the high dose of omega-3 fatty acids and their effect on bleeding, (ii) the fact that cortisone increases their oxidation and may render them proinflammatory, (iii) other antithrombotic microconstituents included in the consumed cod-oil and/or the diet of the subject and (iv) the differences in the coagulation and fibrinolytic systems of well- trained subjects. Further studies are needed to substantiate any possible interaction of cortisone and omega-3 fatty acids in wide ranges of intake.

  2. Splitting hair for cortisol? Associations of socio-economic status, ethnicity, hair color, gender and other child characteristics with hair cortisol and cortisone.

    Science.gov (United States)

    Rippe, Ralph C A; Noppe, Gerard; Windhorst, Dafna A; Tiemeier, Henning; van Rossum, Elisabeth F C; Jaddoe, Vincent W V; Verhulst, Frank C; Bakermans-Kranenburg, Marian J; van IJzendoorn, Marinus H; van den Akker, Erica L T

    2016-04-01

    The aim of this study was to examine associations of SES and ethnicity with hair cortisol and cortisone and to identify potential child and family characteristics that can assist in choosing covariates and potential confounders for analyses involving hair cortisol and cortisone concentrations. Hair samples were collected in 2484 6-year-old children from the Generation R Study, a prospective cohort in Rotterdam, the Netherlands. Measurements for cortisol and cortisone were used as the outcome in regression analyses. Predictors were SES, ethnicity, hair color and child characteristics such as birthweight, gestational age at birth, BMI, disease, allergy, and medication use. Lower family income, more children to be supported by this income, higher BMI and darker hair color were associated with higher hair cortisol and cortisone levels. Boys also showed higher levels. Ethnicity (Dutch and North European descent) was related to lower levels. High amounts of sun in the month of hair collection was related to higher levels of cortisone only. More recent hair washing was related to lower levels of cortisol and cortisone. Gestational age at birth, birth weight, age, medication use, hair washing frequency, educational level of the mother, marital status of the mother, disease and allergy were not associated with cortisol or cortisone levels. Our results serve as a starting point for choosing covariates and confounders in studies of substantive predictors or outcomes. Gender, BMI, income, the number of persons in a household, ethnicity, hair color and recency of hair washing are strongly suggested to take into account. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Automated saliva processing for LC-MS/MS: Improving laboratory efficiency in cortisol and cortisone testing.

    Science.gov (United States)

    Antonelli, Giorgia; Padoan, Andrea; Artusi, Carlo; Marinova, Mariela; Zaninotto, Martina; Plebani, Mario

    2016-04-01

    The aim of this study was to implement in our routine practice an automated saliva preparation protocol for quantification of cortisol (F) and cortisone (E) by LC-MS/MS using a liquid handling platform, maintaining the previously defined reference intervals with the manual preparation. Addition of internal standard solution to saliva samples and calibrators and SPE on μ-elution 96-well plate were performed by liquid handling platform. After extraction, the eluates were submitted to LC-MS/MS analysis. The manual steps within the entire process were to transfer saliva samples in suitable tubes, to put the cap mat and transfer of the collection plate to the LC auto sampler. Transference of the reference intervals from the manual to the automated procedure was established by Passing Bablok regression on 120 saliva samples analyzed simultaneously with the two procedures. Calibration curves were linear throughout the selected ranges. The imprecision ranged from 2 to 10%, with recoveries from 95 to 116%. Passing Bablok regression demonstrated no significant bias. The liquid handling platform translates the manual steps into automated operations allowing for saving hands-on time, while maintaining assay reproducibility and ensuring reliability of results, making it implementable in our routine with the previous established reference intervals. Copyright © 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  4. Carbon isotope ratio analysis of endogenous glucocorticoid urinary metabolites after cortisone acetate and adrenosterone administration for doping control.

    Science.gov (United States)

    Brooker, Lance; Cawley, Adam; Kazlauskas, Ray; Goebel, Catrin; George, Adrian

    2012-12-01

    Glucocorticoids are listed on the World Anti-Doping Agency (WADA) Prohibited List of substances. The detection of the administration of hydrocortisone and cortisone is complicated by the fact that the human body also produces these steroids naturally. Gas chromatography-combustion-isotope ratio mass spectrometry can be utilized to determine the use of endogenous glucocorticoids by measuring the carbon isotope ratio (CIR) of their resulting metabolites in human urine samples. A comprehensive sample preparation protocol for the analysis of endogenous glucocorticoid urinary metabolites was developed and validated, incorporating the use of high performance liquid chromatography (HPLC) for purification and chemical oxidation for derivatisation. Target compounds were tetrahydrocortisol and tetrahydrocortisone, and 11β-hydroxyetiocholanolone, 11-oxoetiocholanolone and 11β-hydroxyandrosterone, while pregnanediol functioned as the endogenous reference compound. Urine samples from a population of 50 volunteers were analyzed to determine CIR reference limits. Excretion studies of the endogenous glucocorticoid preparation cortisone acetate (25 mg oral) and the dietary supplement adrenosterone (75 mg oral) were conducted with six male individuals. Variable changes in steroid metabolite isotopic composition were found across subjects after administration. The study also revealed that CIR analysis of the major glucocorticoid metabolites tetrahydrocortisol and tetrahydrocortisone is necessary to unambiguously distinguish administration of cortisone and adrenosterone, the former officially restricted to out-of-competition use by athletes, the latter not being restricted at the current time. Moreover, this study reaffirms that CIR methods for the doping control of endogenous steroids should not rely upon a single ERC, as the administration of an appropriate precursor to that ERC could cause complications during analysis. Copyright © 2012 John Wiley & Sons, Ltd.

  5. Increased visceral adiposity and cortisol to cortisone ratio in adults with congenital lifetime isolated GH deficiency.

    Science.gov (United States)

    Gomes-Santos, Elenilde; Salvatori, Roberto; Ferrão, Thiago O; Oliveira, Carla R P; Diniz, Rachel D C A; Santana, João A M; Pereira, Francisco A; Barbosa, Rita A A; Souza, Anita H O; Melo, Enaldo V; Epitácio-Pereira, Carlos C; Oliveira-Santos, Alécia A; Oliveira, Ingrid A S; Machado, Julianne A; Santana-Júnior, Francisco J; Barreto-Filho, José A S; Aguiar-Oliveira, Manuel H

    2014-09-01

    Adult-onset GH deficiency (GHD) increases visceral adiposity and the activity of the enzyme 11β-hydroxysteroid dehydrogenase, which converts cortisone (E) to cortisol (F), both linked to insulin resistance and increased cardiovascular risk. Conversely, we reported that adults with congenital isolated GHD (IGHD) have increased insulin sensitivity. To assess the type of fat distribution and the amount of visceral and sc fat and to correlate them to the F/E ratio in adults with untreated IGHD due to a mutation in the GHRH receptor gene. Body composition was assessed by dual-energy x-ray absorptiometry, thickness of sc and visceral fat was measured by sonography, and serum F and E were measured in 23 IGHD subjects and 21 age-matched controls. Waist/hip ratio (WHR), trunk fat, and trunk/extremity fat (TR/EXT) ratio were higher in IGHD subjects. Visceral fat index (VFI) (but not sc fat index [SFI]) was higher in IGHD. F and F/E ratio were also higher in IGHD. In all 44 individuals, WHR correlated with TR/EXT ratio, thickness of visceral fat, VFI/SFI ratio, F, and F/E ratio. TR/EXT ratio correlated with visceral fat thickness, VFI/SFI ratio, and F. Age had a significant effect on VFI and on F/E ratio. Body mass index SD score and WHR have a similar significant effect on TR/EXT ratio and on F/E ratio. Lifetime congenital untreated IGHD causes increased visceral adiposity with a high F/E ratio. However, the increased insulin sensitivity suggests that visceral adiposity needs a minimal GH secretion to translate into increased insulin resistance.

  6. Construction of engineered Arthrobacter simplex with improved performance for cortisone acetate biotransformation.

    Science.gov (United States)

    Zhang, Huitu; Tian, Yao; Wang, Jianling; Li, Yonghai; Wang, Haikuan; Mao, Shuhong; Liu, Xiaoguang; Wang, Chunxia; Bie, Songtao; Lu, Fuping

    2013-11-01

    Arthrobacter simplex 156 is a microorganism that is used for steroid drug biotransformation of cortisone acetate (CA) to prednisone acetate (PA). The enzyme 3-ketosteroid-△(1)-dehydrogenase encoded by the ksdD gene plays an important role in the bioconversion process. To further improve the biotransformation efficiencies of the industrial strain, a genetic manipulation system for A. simplex 156 was developed. Additional copies of the ksdD gene under the control of the cat promoter (from pXMJ19) were transferred into the strain A. simplex 156 and integrated into the 16S rDNA sites, yielding a series of recombinant strains. One of these recombinant strains, designated A. simplex M158, exhibited superior properties for CA biotransformation. At the substrate concentration of 83.6 g/l, the highest PA production of the recombinant strain reached 66.7 g/l, which is approximately 32.9 % higher than that of wild-type strains, and the incubation time for CA to PA bioconversion was reduced by 20 h. Southern blotting analysis of the recombinant strain indicated two copies of deregulated ksdD genes were integrated into the 16S rDNA sites, which means two of five 16S rRNA operons were insertionally disrupted in the recombinant strain. However, the disruption of the two 16S rRNA operons did not affect the growth rate of the recombinant strain, which survived and thrived under desired conditions. In addition, the new strain was genetically stable for more than 100 generations without the use of antibiotics for selection. These superior characteristics make the new strain more suitable than the wild-type strain for PA production.

  7. Simultaneous determination of cortisol, cortisone, 6β-hydroxycortisol and 6β-hydroxycortisone by HPLC.

    Science.gov (United States)

    Zheng, Liyun; Luo, Xi; Zhu, Lijun; Xie, Wenzhao; Liu, Shikun; Cheng, Zeneng

    2015-04-01

    A specific and sensitive method based on high-performance liquid chromatography with ultraviolet absorbance detection (HPLC-UV) was developed for the simultaneous determination of urinary cortisol (F), cortisone (E), 6β-hydroxycortisol (6β-OHF) and 6β-hydroxycortisone (6β-OHE) using dexamethasone as the internal standard. The method involved solid-phase extraction of the five compounds from urine using Oasis HLB Waters cartridges with an elution solvent of ethyl acetate-diethyl ether (5 mL; 4:1, v/v), followed by 1 mol/L of NaOH (1 mL) and 1.0% acetic acid (1 mL). Separation of the five analytes was achieved within 31 min by using a reversed-phase C18 analytical column (200 × 4.6 mm, 5 µm, Agilent). A UV detector operated at 245 nm was used. According to the method validation, inter-run and intra-run precision was below 9.45% and accuracy ranged from 98.16 to 115.50%. The lower limits of quantitation were 5 ng/mL for four analytes. This is the first HPLC method that can simultaneously determine F, E, 6β-OHF and 6β-OHE in human urine. The assay was applied to research the ratio of (6β-OHF + 6β-OHE)/(F + E) as a non-invasive biomarker for the metabolism of tacrolimus. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  8. cortisol/cortisone ratio as a valid tool of training load monitoring

    Directory of Open Access Journals (Sweden)

    T Bouaziz

    2016-08-01

    Full Text Available The effectiveness of selected physiological and perceptual measures for monitoring training load and fatigue was studied in 16 male elite rugby sevens players during a 6-week intense training block (IT and 2-week tapering (TAP. Daily training load (TL and strain (TS as well as weekly total score of fatigue (TSF were quantified respectively by the session-rating of perceived exertion (RPE method and an 8-item questionnaire. Also, testing was performed and 24 h urinary cortisol (C, cortisone (Cn, adrenaline (A and noradrenalin (NA excretion was measured before (T0 and after the IT (T1 and after the TAP (T2. The TL, TS and TSF increased during the IT and decreased during the TAP, in conjunction with a significant drop and improvement, respectively, of performance standards during the two periods. At T1, C and Cn levels increased while A and NA levels decreased, resulting in a higher C/Cn ratio and lower A/NA ratio, respectively. At T2, both C/Cn and A/NA returned to baseline values. The changes in C/Cn ratio, after the 6-week IT, were more closely related to mean TL, TS and TSF (r=0.75-0.76 vs. r=0.48-0.58, p<0.01 and to changes in the majority of performance measures than to A/NA ratio. Only the changes in C/Cn ratio after the 2-week TAP were related to mean TL, TS and TSF (r=0.61-0.68, p<0.01. The changes in hormone levels, training strain and performance standards reflected the physical and mental stressors of training, with complete recovery, as indicated by physiological homeostasis, achieved after an appropriate tapering period.

  9. Human saliva cortisone and cortisol simultaneous analysis using reverse phase HPLC technique.

    Science.gov (United States)

    De Palo, Elio F; Antonelli, Giorgia; Benetazzo, Arianna; Prearo, Maddalena; Gatti, Rosalba

    2009-07-01

    Hyper-hypo tension (like Cushing's syndrome, apparent mineralocorticoid excess syndrome and Addison's disease) diagnostic laboratory requires cortisol (F) analysis. The simultaneous analysis of human saliva F and cortisone (E), the inactive F metabolite, by solid phase extraction and RP-HPLC was studied. Saliva/standard samples were C18-SPE extracted, dried and resuspended. E and F were analysed by isocratic RP-HPLC (acetonitrile/water 27/73%) and UV detection. In the morning and in the evening Salivette stimulated saliva specimens were collected from healthy volunteers. The E and F calibration curve ranges were 11.0-110.0 and 5.5-55.0 nmol/l respectively. The LOD was 0.2 and 0.1 nmol/l for E and F respectively. The intra and inter assay CVs were respectively 2.7-6.6 and 5.6-7.0% for E and 5.8-7.0 and 11.7-13.1% for F. The E and F spiked saliva sample recovery was 99% and 88% respectively. Saliva specimen stability was validated. E and F saliva levels in healthy volunteers were significantly (p<0.001) higher at 8 a.m. compared with 11 p.m. (26.4+/-8.9 vs. 4.3+/-2.9 nmol/l for E; 11.1+/-4.0 vs. 2.5+/-1.5 nmol/l for F, respectively). This method is suitable for periodic analyses in a clinical biochemistry laboratory for endocrinology investigation purposes, simultaneously analysing E and F levels in a saliva specimen.

  10. Conversion of cortisone to cortisol and prostaglandin F2α production by the reproductive tract of cows at the late luteal stage in vivo.

    Science.gov (United States)

    Duong, H T; Skarzynski, D J; Piotrowska-Tomala, K K; Bah, M M; Jankowska, K; Warmowski, P; Łukasik, K; Okuda, K; Acosta, T J

    2012-12-01

    Previous in vitro studies demonstrated that bovine endometrium has the capacity to convert inactive cortisone to biologically active cortisol (Cr) and that Cr inhibits cytokine-stimulated prostaglandin F(2α) (PGF) production. This study was carried out to test the hypothesis that bovine reproductive tract has the capacity to convert cortisone to Cr in vivo and to evaluate the effects of intravaginal application of exogenous cortisone on uterine PGF secretion during the late luteal stage. The temporal relationships between PGF and Cr levels in uterine plasma were also determined. Catheters were inserted into jugular vein (JV), uterine vein (UV), vena cava caudalis (VCC) and aorta abdominalis (AA) of six cows on Day 15 of the oestrous cycle (ovulation = Day 0) for frequent blood collection. On Day 16, the cows were divided randomly into two groups and infused intravaginally with vaseline gel (10 ml; control; n = 3) or cortisone dissolved in vaseline gel (100 mg; n = 3). Blood samples were collected at -2, -1, -0.5, 0, 0.5, 1, 1.5, 2, 3, 4, 5 and 6 h after treatments (0 h). Intravaginal application of cortisone increased plasma concentrations of Cr between 0.5 and 1.5 h in UV, at 0.5 h in VCC, at 1 h in JV and at 1.5 h in AA. The plasma concentrations of PGF in UV and of PGF metabolite in JV were greater at 0.5 and 1 h in the cortisone-treated animals than in control animals. The levels of PGF in UV blood plasma decreased after Cr reached its highest levels. The overall findings suggest that the female reproductive tract has the capacity to convert cortisone to Cr in vivo. Based on the temporal changes of PGF and Cr levels in the uterine plasma, a biphasic response in PGF secretion was found to be associated to the Cr increase induced by the cortisone treatment at the late luteal stage in non-pregnant cows. © 2012 Blackwell Verlag GmbH.

  11. Engineering a hydroxysteroid dehydrogenase to improve its soluble expression for the asymmetric reduction of cortisone to 11β-hydrocortisone.

    Science.gov (United States)

    Zhang, Dalong; Zhang, Rui; Zhang, Jie; Chen, Liying; Zhao, Chunxia; Dong, Wenyue; Zhao, Qing; Wu, Qiaqing; Zhu, Dunming

    2014-11-01

    11β-Hydrocortisone (11β-HC) is an important anti-inflammatory drug and intermediate for the synthesis of other steroids. One of the methods for the synthesis of 11β-HC is the asymmetric reduction of cortisone catalyzed by a highly regioselective and stereoselective 11β-hydroxysteroid dehydrogenase (11β-HSDH). However, this process has been prohibited by the poor soluble expression of the membrane-anchoring protein 11β-HSDH in prokaryotes. To overcome this obstacle, a mutant III-1G1 (Phe80Leu/Thr105Ser/Ala260Thr/Tyr274Stop) truncated at position 274 with improved yield of soluble protein was stepwise obtained from the 11β-HSDH from guinea pig by random mutagenesis combining with structural complementation assay and C-terminal truncating library screening. The improved 11β-HSDH mutant and glucose dehydrogenase (GDH) from Bacillus subtilis were coexpressed in Escherichia coli. The resulting whole-cell biocatalyst catalyzed the reduction of cortisone to 11β-HC with 98 % conversion in 20 h, laying foundation for the development of an asymmetric reduction process for the production of 11β-HC.

  12. Determination of cortisol and cortisone in human saliva by a liquid chromatography-tandem mass spectrometry method.

    Science.gov (United States)

    Vieira, José Gilberto Henriques; Nakamura, Odete Hirata; Carvalho, Valdemir Melechko

    2014-11-01

    Salivary cortisol measurement plays an important role in the evaluation of adrenal function. Its high correlation with free serum cortisol, the easy of sampling and the limited presence of interfering steroids, generated multiple recent studies of its application, in special in the screening of adrenal hyperfunction. In this paper we present our experience in the development of a high pressure liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method for salivary cortisol and cortisone measurement. For this study we used 181 saliva samples from our routine diagnostic laboratory. The HPLC-MS/MS method was based on a Waters Quattro Premier tandem mass spectrometer with an electrospray probe. After derivatization with hydroxylamine transitions monitored included cortisol and cortisone. An in-house radioimmunoassay (RIA) was used for salivary cortisol results comparison. Functional sensitivity was 24 ng/dL for cortisol and linearity from 24 to 1929 ng/dL. Saliva cortisol values obtained in the 181 samples presented a median of 52 ng/dL with 5-95% percentile of 24 and 374 ng/dL. With the RIA the results were 86, 25 and 436 ng/dL, respectively, with values for RIA being significantly higher (PCortisone measured in 159 samples showed a median of 278 ng/dL, with 5-95% percentile of 100 and 1,133 ng/dL. Correlation with cortisol values was significant (r=0.820, Pcortisone measurement and the evaluation of 11βHSD2 activity.

  13. Transuteroplacental metabolism of cortisol and cortisone during mid- and late gestation in the baboon

    Energy Technology Data Exchange (ETDEWEB)

    Pepe, G.J.; Albrecht, E.D.

    1984-11-01

    We measured uterine extraction (i.e. metabolism) and transuteroplacental interconversion of cortisol (F) and cortisone (E) to determine whether metabolism across the uterus changes during pregnancy and contributes to the MCR of these corticosteroids. On day 100 (n . 4) or 170 (n . 3) of pregnancy (term . day 184), baboons (Papio anubis; 14-18 kg) were sedated with ketamine, and a constant infusion (0.38 ml/min) of 8-12 microCi (/sup 3/H)F and 9-15 microCi (/sup 14/C)E in 80 ml 0.9% NaCl-1% ethanol was initiated (time zero) via a maternal antecubital vein. At 60 min, animals were laparotomized, and at 70, 80, and 90 min, blood samples were obtained from right and left uterine veins and from a maternal saphenous vein. At 95 min, a transverse incision was made in the uterus, the fetus was isolated, and blood samples were obtained from the umbilical vein and artery. The cord was then clamped, and the fetus was delivered. Radio-labeled F and E were extracted from serum and purified by sequential paper chromatography, and metabolic parameters were calculated. Endogenous F and E levels were determined by RIA. In the mother, the percent conversions of E to F at midgestation (mean +/- SE; 72 +/- 4) and late gestation (65 +/- 3) were similar and exceeded (P less than 0.01) respective values for oxidation of F to E (51 +/- 7 and 46 +/- 7, respectively), indicating that maternal corticosteroid metabolism favors F formation and is unchanged during the second half of gestation. In contrast, corticosteroid metabolism across the uterus and placenta (transuteroplacental) was altered during pregnancy. At midgestation, transuteroplacental conversion of E to F (37 +/- 9) exceeded (P less than 0.05) the reverse reaction (18 +/- 3), whereas oxidation of F to E at term (28 +/- 4) was 7-fold greater (P less than 0.05) than reduction of E to F (4 +/- 1).

  14. Glucocorticoid Metabolism in Hypertensive Disorders of Pregnancy: Analysis of Plasma and Urinary Cortisol and Cortisone.

    Science.gov (United States)

    Kosicka, Katarzyna; Siemiątkowska, Anna; Krzyścin, Mariola; Bręborowicz, Grzegorz H; Resztak, Matylda; Majchrzak-Celińska, Aleksandra; Chuchracki, Marek; Główka, Franciszek K

    2015-01-01

    The aim of the study was to analyze the plasma and urinary cortisol (F) and cortisone (E) levels in normotensive and hypertensive pregnant women. The parameters known to reflect the function of 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) were calculated to verify the changes in glucocorticoid balance over the course of gestational hypertension (GH) and pre-eclampsia (PE). This retrospective case-control study included women in the third trimester of pregnancy, diagnosed with: GH (n = 29), PE (n = 26), or chronic hypertension (CH; n = 22). Normotensive women in their third trimester of pregnancy were also included (controls; n = 43). The plasma and urinary F and E levels were measured with the HPLC-FLD method. The 11β-HSD2 function was estimated by calculating the following ratios: plasma F/E and urinary free F to urinary free E (UFF/UFE). A statistical analysis was performed based on case-control structure. PE was characterized by lower plasma F levels (639.0 nmol/L), UFF/Cr levels (3.80 μg/mmol) and F/E ratio (3.46) compared with that of the controls (811.7 nmol/L, 6.28 μg/mmol and 5.19, respectively) with marked abnormalities observed in the changes of F/E and UFF/UFE ratios with advancing gestation. GH patients showed significant disparities in the urinary steroid profile with lower UFF/UFE ratio (0.330 vs. 0.401) compared with the normotensive controls and abnormal changes in the UFF/UFE throughout pregnancy. The observed tendency towards lower F/E and UFF/UFE ratios in PE and GH patients may reflect more intensive F metabolism over the course of those disorders. In the normal pregnancy group, the plasma F/E and UFF/UFE ratios tended to present inverse correlations with advancing gestation. This trend was much less marked in PE and GH patients, suggesting that the abnormalities in 11β-HSD2 functions progressed with the GA. The birth weights of neonates born from pre-eclamptic pregnancies were lower than those from uncomplicated pregnancies

  15. Controlled release of cortisone drugs from block copolymers synthetized by ATRP

    Science.gov (United States)

    Valenti, G.; La Carta, S.; Mazzotti, G.; Rapisarda, M.; Perna, S.; Di Gesù, R.; Giorgini, L.; Carbone, D.; Recca, G.; Rizzarelli, P.

    2016-05-01

    Diseases affecting posterior eye segment, like macular edema, infection and neovascularization, may cause visual impairment. Traditional treatments, such as steroidal-drugs intravitreal injections, involve chronic course of therapy usually over a period of years. Moreover, they can require frequent administrations of drug in order to have an adequately disease control. This dramatically reduce patient's compliance. Efforts have been made to develop implantable devices that offer an alternative therapeutic approach to bypass many challenges of conventional type of therapy. Implantable drug delivery systems (DDS) have been developed to optimize therapeutic properties of drugs and ensure their slow release in the specific site. Polymeric materials can play an essential role in modulating drug delivery and their use in such field has become indispensable. During last decades, acrylic polymers have obtained growing interest. Biocompatibility and chemical properties make them extremely versatile, allowing their use in many field such as biomedical. In particular, block methacrylate copolymer with a balance of hydrophilic and hydrophobic properties can be suitable for prolonged DDS in biomedical devices. In this work, we focused on the realization of a system for controlled and long term release of betamethasone 17,21-dipropionate (BDP), a cortisone drug, from methacrylic block copolymers, to be tested in the treatment of the posterior eye's diseases. Different series of methyl methacrylate/hydroxyethyl methacrylate (MMA/HEMA) block and random copolymers, with different monomer compositions (10-60% HEMA), were synthetized by Atom Transfer Radical Polymerization (ATRP) to find the best hydrophilic/hydrophobic ratio, able to ensure optimal kinetic release. Copolymer samples were characterized by NMR spectroscopy (1H-NMR, 13C-NMR, CosY), SEC, TGA and DSC. Monitoring of drug release from films loaded with BDP was carried out by HPLC analysis. Evaluation of different kinetic

  16. Controlled release of cortisone drugs from block copolymers synthetized by ATRP

    Energy Technology Data Exchange (ETDEWEB)

    Valenti, G.; La Carta, S.; Rapisarda, M.; Carbone, D.; Recca, G.; Rizzarelli, P., E-mail: paola.rizzarelli@cnr.it [Istituto per i Polimeri, Compositi e Biomateriali, Consiglio Nazionale delle Ricerche Via P. Gaifami 18, 95129 Catania (Italy); Mazzotti, G.; Giorgini, L. [Dipartimento di Chimica Industriale «Toso Montanari», Università di Bologna Via Risorgimento 4, 40136 Bologna (Italy); Perna, S. [ST Microelectronics Srl, Stradale Primosole, 50–95121 Catania (Italy); Di Gesù, R. [Merck Serono S.p.A., Via L. Einaudi, 11–00012 Guidonia Montecelio, Rome (Italy)

    2016-05-18

    Diseases affecting posterior eye segment, like macular edema, infection and neovascularization, may cause visual impairment. Traditional treatments, such as steroidal-drugs intravitreal injections, involve chronic course of therapy usually over a period of years. Moreover, they can require frequent administrations of drug in order to have an adequately disease control. This dramatically reduce patient’s compliance. Efforts have been made to develop implantable devices that offer an alternative therapeutic approach to bypass many challenges of conventional type of therapy. Implantable drug delivery systems (DDS) have been developed to optimize therapeutic properties of drugs and ensure their slow release in the specific site. Polymeric materials can play an essential role in modulating drug delivery and their use in such field has become indispensable. During last decades, acrylic polymers have obtained growing interest. Biocompatibility and chemical properties make them extremely versatile, allowing their use in many field such as biomedical. In particular, block methacrylate copolymer with a balance of hydrophilic and hydrophobic properties can be suitable for prolonged DDS in biomedical devices. In this work, we focused on the realization of a system for controlled and long term release of betamethasone 17,21-dipropionate (BDP), a cortisone drug, from methacrylic block copolymers, to be tested in the treatment of the posterior eye’s diseases. Different series of methyl methacrylate/hydroxyethyl methacrylate (MMA/HEMA) block and random copolymers, with different monomer compositions (10–60% HEMA), were synthetized by Atom Transfer Radical Polymerization (ATRP) to find the best hydrophilic/hydrophobic ratio, able to ensure optimal kinetic release. Copolymer samples were characterized by NMR spectroscopy ({sup 1}H-NMR, {sup 13}C-NMR, CosY), SEC, TGA and DSC. Monitoring of drug release from films loaded with BDP was carried out by HPLC analysis. Evaluation of

  17. Combined quantification of corticotropin-releasing hormone, cortisol-to-cortisone ratio and progesterone by liquid chromatography-Tandem mass spectrometry in placental tissue.

    Science.gov (United States)

    Fahlbusch, Fabian B; Ruebner, Matthias; Rascher, Wolfgang; Rauh, Manfred

    2013-09-01

    With mid-gestation the production of placental corticotropin-releasing hormone (CRH) starts to steadily increase. The fetal peptide CRH excerts direct functions at the feto-maternal interface (vasodilatation, timing of birth) via its interaction with progesterone and indirectly ensures maturation and growth of fetal organ systems for delivery by driving fetal cortisol production via its induction of adrenocorticotropic hormone release. This feedback loop is tightly controlled by the amount of enzymatic cortisol/cortisone turnover in the placental syncytiotrophoblast by 11β-hydroxy-steroid dehydrogenase type 2 (11β-HSD2). Traditionally, placental tissue hormones have been quantified by immunological methods (e.g. RIA or ELISA), which have the drawback of possible cross-reactivity and tissue perturbations. Most importantly, it is not possible to quantify CRH and steroid hormones, such as cortisol, cortisone and progesterone together in the same sample with these methods. Hence, we aimed to develop and validate a quantitative mass spectrometry (MS) method for multi-modal quantification of these placental hormones: While CRH was readily detectable throughout the placenta, the placental levels of progesterone and especially cortisol and cortisone were higher at the placental base facing the maternal side. The HPLC-MS/MS procedure showed excellent selectivity and sufficient limit of quantification in placental tissue homogenates to allow for simultaneous detection of CRH, cortisol and cortisone, and progesterone. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. [Susceptibility of the Chinese hamster (Cricetulus griseus) to parasitic infection (3). Experimental infection with Hymenolepis nana or Trichuris muris to the cortisone treated Chinese hamster].

    Science.gov (United States)

    Kutsumi, H; Miyamoto, K; Inaoka, T

    1989-07-01

    Susceptibility of Chinese hamster (Cricetulus griseus) of Asahikawa Colony (CHA) to Hymenolepis nana or Trichuris muris infection was compared in the feces-egg examination with that of mice as the control animals. Though CHA were resistant to the infection of H. nana, they were found to become susceptible to H. nana by the treatment with cortisone. A half number of CHA was infected with H. nana and the eggs were detected from each animal only in 4 or 6 days in the periods of examination more than 40 days. Mice with or without cortisone treatment were equally susceptible to H. nana infection. In another experiment, CHA with or without cortisone treatment were completely resistant to Trichuris muris infection. Mice, as the control animals, were found to be infected with T. muris in both of cortisone-treated and non-treated groups. Results from the fecal examination, it was confirmed that T. muris were expelled naturally from the animals on the weeks of 11 to 33 after infection.

  19. 11β-Hydroxysteroid dehydrogenase activity in the brain does not contribute to systemic interconversion of cortisol and cortisone in healthy men.

    Science.gov (United States)

    Kilgour, Alixe H M; Semple, Scott; Marshall, Ian; Andrews, Peter; Andrew, Ruth; Walker, Brian R

    2015-02-01

    11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) catalyses regeneration of cortisol in liver, adipose tissue, and skeletal muscle, making a substantial contribution to circulating cortisol as demonstrated in humans by combining stable isotope tracer infusion with arteriovenous sampling. In the brain, 11βHSD1 is a potential therapeutic target implicated in age-associated cognitive dysfunction. We aimed to quantify brain 11βHSD1 activity, both to assess its contribution to systemic cortisol/cortisone turnover and to develop a tool for measuring 11βHSD1 in dementia and following administration of 11βHSD1 inhibitors. With ethical approval and informed consent, 8 healthy men aged 38.1 years (sd 16.5) underwent an ECG-gated phase-contrast magnetic resonance scan to quantify internal jugular vein blood flow and were infused with 1,2 [(2)H]2-cortisone and 9,11,12,12 [(2)H]4-cortisol for 3 h before samples were obtained from the internal jugular vein and an arterialized hand vein. Steroids were quantified by liquid chromatography-tandem mass spectrometry. Steady state tracer enrichments were achieved and systemic indices of cortisol/cortisone interconversion were consistent with previous studies in healthy men. However, there was no measurable release or production of cortisol, 9,12,12 [(2)H]3-cortisol or cortisone into the internal jugular vein. Although cerebral 11βHSD1 reductase activity may be greater in cognitively impaired patients, in healthy men any contribution of 11βHSD1 in the brain to systemic cortisol/cortisone turnover is negligible. The influence of 11βHSD1 in the brain is likely confined to subregions, notably the hippocampus. Alternative approaches are required to quantify pharmacodynamics effects of 11βHSD1 inhibitors in the human brain.

  20. Highly selective and automated online SPE LC-MS3 method for determination of cortisol and cortisone in human hair as biomarker for stress related diseases.

    Science.gov (United States)

    Quinete, Natalia; Bertram, Jens; Reska, Marcus; Lang, Jessica; Kraus, Thomas

    2015-03-01

    Hair analysis has been increasingly used to establish long-term biomarkers of exposure to both endogenous and exogenous substances, with a special emphasis on steroidal hormones. Hair cortisol and cortisone have been associated to physiological and psychological strains, anxiety and depression. Hair is a very complex matrix, which might jeopardize analyte detection at low concentrations. A new, highly selective and sensitive method based on fragments of second order, MS(3) (MS/MS/MS), was developed and validated for the analysis of hair cortisol and cortisone. An online solid phase extraction was performed on a C8 restricted access material (RAM) phase following by separation on a reversed-phase C18 column using methanol and 0.02% ammonium hydroxide as mobile phase. The developed method required minimal sample preparation and the injection of only 50 µL of sample leading to a LOQ of 2 pg mg(-1). Good linear responses were observed in the range 2-200 pg mg(-1) (R(2)>0.99) and extraction recoveries ranged between 77-125% and 70-123% for cortisol and cortisone, respectively. Intra- and inter-assay coefficients of variation were between 1.4 and 14%. In order to evaluate the applicability of the method, preliminary tests (N=33) were conducted in 3 cm hair samples (close to scalp) of healthy volunteers with an age range of 4-63. Average concentrations in hair were 12.7±14 pg mg(-1) and 41.6±42 pg mg(-1) for cortisol and cortisone, respectively. Further investigations on cortisol and cortisone as biomarkers for chronic psychological strain will be assessed as a next step. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Simultaneous measurement of cortisol and cortisone in human saliva using liquid chromatography-tandem mass spectrometry: application in basal and stimulated conditions.

    Science.gov (United States)

    Perogamvros, Ilias; Owen, Laura J; Newell-Price, John; Ray, David W; Trainer, Peter J; Keevil, Brian G

    2009-11-01

    Immunoassays used for the measurement of salivary cortisol are limited by variable interference from cortisone. Salivary cortisone is a consequence of the salivary glands expressing 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) which converts cortisol to cortisone. We report a combined salivary cortisol and cortisone (SalF and SalE respectively) liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay to address the cortisone cross-reactivity in cortisol immunoassays and as a tool to study 11beta-HSD2 activity. The method was linear up to 400 nmol/L for SalF and 200 nmol/L for SalE and the lower limits of quantitation were 0.39 nmol/L (SalF) and 0.78 nmol/L (SalE). No evidence of ion suppression was found and precision, accuracy and recovery were within internationally accepted limits. No interference was identified from 13 structurally related steroids. SalF, SalE and SalF/SalE were significantly greater in the morning than at bed-time and following stimulation of the adrenal glands. As serum cortisol increased, an exponential rise was observed in SalF and a linear increase in SalE which reached a plateau at higher SalF concentrations. We have developed a novel, robust LC-MS/MS assay for the combined measurement of SalF and SalE. Our results confirm the 11beta-HSD2 activity of the salivary glands resulting in high SalE concentrations and the enzyme saturation at high substrate concentrations. This method can be used as a simple, non-invasive and highly specific tool to assess the value of salivary cortisol as a surrogate for free serum cortisol and as a potential novel way to assess 11beta-HSD2 activity.

  2. Arterial and venous thromboses in patients with idiopathic (immunological) thrombocytopenia: a possible contributing role of cortisone-induced hypercoagulable state.

    Science.gov (United States)

    Girolami, Antonio; de Marinis, Gulia Berti; Bonamigo, Emanuela; Treleani, Martina; Vettore, Silvia

    2013-01-01

    Immunological thrombocytopenias, as other forms of thrombocytopenia, are associated with bleeding. Occasionally, these patients manifest thrombotic events. A total of at least 29 patients were reported to have had either arterial (20 cases) or venous (9 cases) thrombosis while platelet count was less than 50 × 10(3)/μL. The most frequent clinical manifestation was a myocardial infarction. Thrombosis occurred in the large majority of patients during prednisone therapy. Patients receiving cortisone or patients with Cushing syndrome show a hypercoagulable state characterized by elevated factor VIII levels, decreased fibrinolysis, and abnormal von Willebrand factor multimers composition. The same is probably true for prednisone-treated patients with thrombocytopenia. However, the 2 conditions are not identical since prednisone is a mainly glycoactive compound, whereas cortisol produced in excess in Cushing syndrome is mainly mineraloactive. The presence of large, young, hyperactive platelets may also play a role. Prednisone-treated patients with thrombocytopenia have to be considered as potentially thrombophilic.

  3. Validation and application of a highly specific and sensitive ELISA for the estimation of cortisone in saliva, urine and in vitro cell-culture media by using a novel antibody.

    Science.gov (United States)

    Al-Dujaili, Emad A S; Baghdadi, Hussam H S; Howie, Forbes; Mason, J Ian

    2012-05-01

    It is generally acknowledged that local tissue concentrations of cortisol and cortisone are modulated by site-specific actions of 11β-hydroxysteroid dehydrogenase (11β-HSD) isoenzymes 1 and 2. Cortisone, the inactive metabolite of cortisol is produced by 11βHSD type 2. To assess 11β-HSD types 1 and 2 activities, the cortisol/cortisone ratio has to be accurately determined. Immunoassays to measure cortisone levels are not widely available and tend to lack specificity. The aim of this project was to develop a highly specific and sensitive ELISA method for the estimation of free cortisone levels in urine, saliva and in vitro media samples without chromatographic separation. Antibodies against cortisone were raised in rabbits using cortisone-3-CMO-KLH as immunogen. HRP-goat anti-rabbit IgG conjugate was used as enzyme tracer. Cross-reactivities of the untreated cortisone antiserum with major interfering steroids were minimal except for cortisol (3.15%). However, following an immune-affinity purification of the antibodies using CNBr-activated sepharose-cortisol-3-CMO-BSA, cross-reactivity of the purified cortisone antibody with cortisol was reduced to 0.27%. The minimum detection limit of cortisone ELISA was 28 pg/mL (77.7 pM). The validity of the cortisone ELISA was confirmed by the excellent correlation obtained before and after an HPLC fractionation step (Y=1.09X-0.21, R2=0.98). Intra-assay and inter-assay imprecision were 5.5-11.7% and 8.7-12.8% CV, respectively. Using this assay, salivary cortisone levels showed a circadian rhythm in men and women (11.2±7.3 nM at 08.00 h and 5.1±3.6 nM at 18.00 h), and the levels were reduced following liquorice ingestion. In media of adrenocortical H295 cell line incubations, basal cortisone levels were 4.24±0.22 nM that increased to 8.6±1.2 nM post forskolin treatment. Urinary free cortisone excretion levels in healthy subjects were 56.66±36.9 nmol/day. In human volunteers following ingestion of green coffee bean extract

  4. 11beta-Hydroxysteroid dehydrogenase type 1-driven cortisone reactivation regulates plasminogen activator inhibitor type 1 in adipose tissue of obese women.

    Science.gov (United States)

    Ayachi, S Ei; Paulmyer-Lacroix, O; Verdier, M; Alessi, M-C; Dutour, A; Grino, M

    2006-03-01

    Plasminogen activator inhibitor type 1 (PAI-1) is the main inhibitor of the fibrinolytic system and contributes to an increased risk of atherothrombosis in insulin-resistant obese patients. In adipose tissue, we have shown that PAI-1 is synthesized mainly in the visceral stromal compartment and is positively regulated by glucocorticoids. We have demonstrated that adipose tissue expression of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD-1), an enzyme that catalyzes the conversion of inactive cortisone to active cortisol, is exaggerated in obese patients. We hypothesized that increased action of 11beta-HSD-1 in adipose tissue of obese subjects may contribute to PAI-1 overproduction. Using in situ hybridization, we studied the expression of the mRNAs coding for PAI-1 and 11beta-HSD-1 in the stromal compartment of visceral adipose tissue obtained from obese women. The regulation of PAI-1 secretion from in vitro incubated tissue explants was also investigated. Regression analysis showed a significant positive linear relationship between PAI-1 and 11beta-HSD-1 mRNAs expression. In vitro incubation of adipose tissue explants demonstrated that cortisone stimulated PAI-1 gene expression and secretion, and that these effects were inhibited by co-incubation with the 11beta-HSD inhibitor, glycyrrhetinic acid. Our data demonstrate that 11beta-HSD-1-driven cortisone reactivation regulates adipose PAI-1 synthesis and secretion. They suggest that the increased PAI-1 synthesis and secretion observed in obese patients can be also related, at least in part, to an increased local conversion of cortisone to cortisol. Therefore, local cortisol metabolism in adipose tissue may be involved in increasing the risk of cardiovascular disease in obese subjects.

  5. The balance of cortisol-cortisone interconversion is shifted towards cortisol in neonates with congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

    Science.gov (United States)

    Kamrath, Clemens; Hartmann, Michaela F; Wudy, Stefan A

    2014-09-01

    Patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency (21OHD) have an impaired cortisol synthesis, but it is unknown whether the metabolism of glucocorticoids differs between neonates and infants with and without 21OHD. The objective of this study was to compare the glucocorticoid metabolism between neonates and infants with and without 21OHD. We analyzed 14 urinary glucocorticoid metabolites, 7 metabolites each of cortisol and cortisone, by gas chromatography-mass spectrometry of 89 untreated 21OHD neonates and infants and 161 neonates and infants without 21OHD. Neonates with 21OHD exhibit elevated relative amounts of cortisol metabolites in total glucocorticoid metabolism and an increased ratio of cortisol to cortisone metabolites (pcortisone. The ratio of cortisol to cortisone metabolites correlated significantly with low urinary glucocorticoid concentrations (pcortisone to cortisol interconversion in neonates with 21OHD. The shift of glucocorticoid metabolism toward active cortisol in neonates with 21OHD seems to be related to the severity of 21OHD and adrenal dysfunction. Our data provide new insights into the regulation of glucocorticoid homeostasis in 21OHD. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Affective alterations in patients with Cushing's syndrome in remission are associated with decreased BDNF and cortisone levels.

    Science.gov (United States)

    Valassi, E; Crespo, I; Keevil, B G; Aulinas, A; Urgell, E; Santos, A; Trainer, P J; Webb, S M

    2017-02-01

    Affective alterations and poorer quality of life often persist in patients with Cushing's syndrome (CS) in remission. Brain-derived neurotrophic factor (BDNF) regulates the hypothalamic-pituitary-adrenal axis (HPA) and is highly expressed in brain areas controlling mood and response to stress. Our aims were to assess affective alterations after long-term remission of CS and evaluate whether they are associated with serum BDNF, salivary cortisol (SalF) and/or cortisone (SalE) concentrations. Thirty-six CS patients in remission (32 females/4 males; mean age (±s.d.), 48.8 ± 11.8 years; median duration of remission, 72 months) and 36 gender-, age- and BMI-matched controls were included. Beck Depression Inventory-II (BDI-II), Center for Epidemiological Studies Depression Scale (CES-D), Positive Affect Negative Affect Scale (PANAS), State-Trait Anxiety Inventory (STAI), Perceived Stress Scale (PSS) and EuroQoL and CushingQoL questionnaires were completed and measured to evaluate anxiety, depression, stress perception and quality of life (QoL) respectively. Salivary cortisol was measured using liquid chromatography/tandem mass spectrometry (LC/TMS). BDNF was measured in serum using an ELISA. Remitted CS patients showed worse scores in all questionnaires than controls: STAI (P cortisone was inversely associated with trait anxiety (r = -0.377, P = 0.040) and depressed affect (r = -0.392, P = 0.032) in CS patients. Delay to diagnosis was associated with depressive symptoms (BDI-II: r = 0.398, P = 0.036 and CES-D: r = 0.449, P = 0.017) and CushingQoL scoring (r = -0.460, P < 0.01). Low BDNF levels are associated with affective alterations in 'cured' CS patients, including depression, anxiety and impaired stress perception. Elevated levels of SalE might also be related to poor affective status in these patients. © 2017 European Society of Endocrinology.

  7. Salivary cortisol and cortisone by LC-MS/MS: validation, reference intervals and diagnostic accuracy in Cushing's syndrome.

    Science.gov (United States)

    Antonelli, Giorgia; Ceccato, Filippo; Artusi, Carlo; Marinova, Mariela; Plebani, Mario

    2015-12-07

    The Endocrine Society recommends late-night salivary cortisol (LNS-F) as a first-line screening test for Cushing's syndrome (CS). In the parotid gland, 11β-hydroxysteroid dehydrogenase type 2 inactivates cortisol (F) to cortisone (E), a known source of interference in the more frequently used immunoassays. A highly specific method is mandatory in determining salivary F and E: it is widely accepted that liquid chromatography-tandem mass spectrometry (LC-MS/MS) is the best available technique for this purpose. A LC-MS/MS method with SPE of saliva samples was developed and validated. Appropriate awakening and bedtime reference ranges were established. The diagnostic performance for F, E and the ratio at bedtime was evaluated in 25 cases of CS. The method was linear, with up to 55.4 nmol/L and 51.0 nmol/L, LLOQ of 0.51 nmol/L and 0.55 nmol/L, for F and E, respectively. Within-run and between-run imprecisions were <10% for both analytes. No ion suppression was observed. A cut-off of 2.4 nmol/L for LNS-F yielded a sensitivity of 100% and a specificity of 98% in the diagnosis of CS. The analytical performance of this method justifies its introduction into clinical practice, thus allowing clinicians the opportunity to further investigate CS and other endocrine diseases. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Pharmacological evaluation of adipose dysfunction via 11β-hydroxysteroid dehydrogenase type 1 in the development of diabetes in diet-induced obese mice with cortisone pellet implantation.

    Science.gov (United States)

    Akiyama, Nobuteru; Akiyama, Yuko; Kato, Hideaki; Kuroda, Takayuki; Ono, Takashi; Imagawa, Keiichi; Asakura, Kenji; Shinosaki, Toshihiro; Murayama, Toshihiko; Hanasaki, Kohji

    2014-04-01

    Signals from intracellular glucocorticoids (GCs) via 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in adipose tissues have been reported to serve as amplifiers leading to deterioration of glucose metabolism associated with obesity. To elucidate adipose dysfunction via 11β-HSD1 activation in the development of obesity-related diabetes, we established novel diabetic mice by implanting a cortisone pellet (CP) in diet-induced obesity (DIO) mice. Cortisone pellet-implanted DIO mice (DIO/CP mice) showed hyperglycemia, insulin resistance, hyperlipidemia, and ectopic fat accumulation, whereas cortisone pellet implantation in lean mice did not induce hyperglycemia. In DIO/CP mice, indexes of lipolysis such as plasma glycerol and nonesterified fatty acids (NEFAs) increased before hyperglycemia appeared. Furthermore, the adipose mRNA level of 11β-HSD1 was up-regulated in DIO/CP mice compared with sham-operated DIO mice. RU486 (mifepristone, 11β-[p-(dimethylamino)phenyl]-17β-hydroxy-17-(1-propynyl)estra-4,9-dien-3-one), a glucocorticoid receptor antagonist, decreased adipose mRNA levels of 11β-HSD1 as well as adipose triglyceride lipase. RU486 also improved plasma NEFA, glycerol, and glucose levels in DIO/CP mice. These results demonstrate that lipolysis in adipose tissues caused by GC activation via 11β-HSD1 serves as a trigger for diabetes with ectopic fat accumulation. Our findings also indicate the possibility of a vicious circle of GC signals via 11β-HSD1 up-regulation in adipose tissues, contributing to deterioration of glucose metabolism to result in diabetes. Our DIO/CP mouse could be a suitable model of type 2 diabetes to evaluate adipose dysfunction via 11β-HSD1.

  9. Simultaneous determination of hair cortisol, cortisone and DHEAS with liquid chromatography-electrospray ionization-tandem mass spectrometry in negative mode.

    Science.gov (United States)

    Chen, Zheng; Li, Jifeng; Zhang, Jing; Xing, Xue; Gao, Wei; Lu, Zuhong; Deng, Huihua

    2013-06-15

    The present study aimed to develop a novel method for simultaneous assay of cortisol, cortisone and dehydroepiandrosterone sulfate (DHEAS) in human hair. The method was based on liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-MS/MS) in negative mode. Analytes were extracted from 20-mg hair incubated in 1ml of methanol for 5 days. 100μl non-SPE supernatant of the incubation solution was utilized in LC-MS/MS analysis. The liquid chromatography separation was performed on a reversed-phase C18 column with a mobile phase of 80:20 (v:v) methanol and deionized water containing 0.1% formic acid. The use of ESI in negative mode and the use of a small volume of the incubation solution significantly improved assay sensitivity. The linear range was 5-250pg/mg for cortisol and cortisone, and 5-500pg/mg for DHEAS. The limit of detection was 2pg/mg for the three analytes in hair. The coefficients of variation for intra-day and inter-day assay were less than 10%. The method was applied to determine the three analytes mentioned above of hair samples from 103 participants. The results indicated that there was no significant effect of age and education level on the hair cortisol, cortisone and DHEAS levels. The simple treatment procedure developed in the present study may facilitate simultaneous measurement of more steroids in hair. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. Improved determination of urinary cortisol and cortisone, or corticosterone and 11-dehydrocorticosterone by high-performance liquid chromatography with ultraviolet absorbance detection.

    Science.gov (United States)

    Hay, M; Mormède, P

    1997-11-21

    A sensitive assay was developed for the determination of low levels of free (unconjugated) glucocorticoids in human, swine (cortisol and cortisone) and rat urine (corticosterone and 11-dehydrocorticosterone), using solid-phase extraction and HPLC with UV absorbance detection (254 nm). Precise quantitation is allowed by the use of internal standards (dexamethasone for swine urine and Reichstein's substance S for rat urine). This simple method allows the use of small urine samples (less than 2 ml), and is suitable for a wide range of applications in human and animal clinical and physiological studies.

  11. Simultaneous determination of urinary cortisol, cortisone and corticosterone in parachutists, depressed patients and healthy controls in view of biomedical and pharmacokinetic studies.

    Science.gov (United States)

    Plenis, Alina; Konieczna, Lucyna; Olędzka, Ilona; Kowalski, Piotr; Bączek, Tomasz

    2011-05-01

    A rapid and sensitive reversed-phase liquid chromatographic method (RP-LC) with UV detection has been developed for the determination of free cortisol, cortisone and corticosterone in human urine. The assay was performed after a solid-phase extraction procedure (SPE) with dexamethasone as the internal standard. Chromatographic separation was carried out on a Nucleosil 100 C(18) analytical column using a mixture of acetonitrile and water (30 : 70, v/v) as a mobile phase at a flow-rate of 1 mL min(-1). Spectrophotometric detection was performed at 240 nm. The method has been validated for accuracy, precision, selectivity, linearity, recovery and stability. The absolute recoveries of glucocorticoids were above 94.6%. The limits of detection (LOD) and quantification (LOQ) were 0.5 and 2 ng mL(-1), respectively, for all analytes. Linearity was confirmed in the range of 2-300 ng mL(-1) with a correlation coefficient greater than 0.9997 for all steroid hormones. The proposed method was sensitive, robust and specific allowing reliable quantification of steroid hormones. This method was successfully applied for determination of three endogenous glucocorticoid levels in human urine. The studies were performed on 20 sedentary healthy volunteers in comparison to two socially diversified groups, namely 10 parachutists before and after jump and 10 patients with depression. Pharmacokinetic studies performed on these groups indicated that urinary free cortisol and cortisol-to-cortisone ratios can be treated as biomarkers of stress and depressive disorders.

  12. UHPLC-MS/MS bioanalysis of urinary DHEA, cortisone and their hydroxylated metabolites as potential biomarkers for CYP3A-mediated drug-drug interactions.

    Science.gov (United States)

    Zheng, Naiyu; Christopher, Lisa J; Ma, Xuewen; Ji, Qin C; Buzescu, Adela; Kandoussi, Hamza; Garonzik, Samira M; LaCreta, Frank; Aubry, Anne-Francoise; Arnold, Mark E; Zeng, Jianing

    2016-12-01

    A UHPLC-MS/MS assay was developed to quantify urinary dehydroepiandrosterone (DHEA), 7β-hydroxy-DHEA, cortisone and 6β-hydroxycortisone as potential biomarkers to predict CYP3A activity. A sensitive assay at LLOQ of 0.500 ng/ml with good accuracy and precision was developed for the four analytes in human urine. This UHPLC-MS/MS assay was optimized by eliminating nonspecific loss of the analytes in urine, ensuring complete hydrolysis of the conjugates to unconjugated forms and use of the product ions of [M+H-H2O](+) for multiple reaction monitoring detection of DHEA and 7β-hydroxy-DHEA. This assay was successfully applied to a pilot clinical study. It is also suitable for future drug-drug interaction studies to continue evaluating the potential of these steroids as biomarkers for CYP3A inhibition and induction.

  13. Determination of urinary cortisol, cortisone and 6-sulfatoxymelatonin using dilute and shoot ultra-high pressure liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Sniecinska-Cooper, Anna Maria; Shah, Ajit Jesang; Dimitriou, Dagmara; Iles, Ray Kruse; Butler, Stephen Andrew; Bayford, Richard

    2015-01-26

    Human sleep is a natural part of every individual's life. Clear relationship between sleep and endocrine system has been already established. In particular, melatonin and cortisol are known to affect and regulate sleep/wake patterns. Here we report the development of an ultra-high pressure liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for simultaneous measurement of 6-sulfatoxymelatonin (MT6s), cortisol and cortisone in urine. A separate method was developed for measurement of creatinine in urine. These levels were used to normalise the levels of analytes. First void morning urine samples were collected from 24 healthy volunteers. Samples were diluted 1:1 in water prior to injection onto reversed-phase C18 column and analysed using UHPLC-MS/MS method. Linear calibrations were obtained for all analytes with correlation coefficient in the range 0.998-0.999. The observed concentration was found to be in the range 92-105% for cortisol, 92-107% for cortisone and between 93 and 120% for MT6s of the reference levels. The total run time of 6 min with all peaks of interest eluting within 3 min was obtained. This demonstrates the feasibility of utilising the method for large multi-scale studies, where high throughput is required for studying the circadian rhythm of melatonin and cortisol secretion. These hormones play significant role in circadian rhythm and sleep/wake cycle; therefore it is important to monitor the levels of these endocrine markers in individuals suffering from sleep disorders. It is also beneficial with clinical applications to analyse melatonin and cortisol simultaneously in order to assess their interrelationships of these substances, such as their effect on diurnal rhythm and sleep. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Simultaneous measurements of cortisol and cortisone in urine and hair for the assessment of 11β-hydroxysteroid dehydrogenase activity among methadone maintenance treatment patients with LC-ESI-MS/MS.

    Science.gov (United States)

    Chen, Zheng; Li, Jifeng; Xu, Guanyi; Yang, Jin; Zhang, Jing; Deng, Huihua

    2014-10-15

    The activity of 11β-hydroxysteroid dehydrogenases (11β-HSD) is traditionally assessed using the ratio of cortisol to cortisone in urine or saliva. However, these biomarkers only reflect the local activity of 11β-HSD, and are easily affected by circadian variation of cortisol secretion. The shortcomings might be overcome by hair analysis. The present study aimed to develop an enhanced assay for simultaneous measurements of cortisol and cortisone in both hair and urine samples. The samples were collected from 29 patients under methadone maintenance treatment. The cortisol and cortisone were extracted either by solid phase extraction from a 20-mg milled hair sample after a 14-h incubation in 1ml of methanol, or by twice liquid-liquid extraction from a 20-fold diluted urine sample. The analyses were performed using high performance liquid chromatography tandem mass spectrometry with electrospray ionization in negative mode. Limits of detection and quantification were 0.5 and 1.25pg/mg for hair steroids and 0.2 and 0.5ng/ml for urinary steroids, respectively. The recoveries were more than 97%. The intra- and inter-day coefficients of variation were less than 10%. The ratios of cortisol to cortisone in hair and urine were both less than one, but did not correlate with each other. A possible reason for the lack of correlation was that the ratios in hair and urine might mostly reflect the activity of 11β-HSD type 2 in the eccrine sweat gland and in the kidney, respectively. Additionally, a significant correlation was observed between results obtained using external standard quantification and internal standard quantification. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. The effect of water loading on the urinary ratio of cortisone to cortisol in healthy subjects and a new approach to the evaluation of the ratio as an index for in vivo human 11β-hydroxysteroid dehydrogenase 2 activity.

    Science.gov (United States)

    Yokokawa, Akitomo; Takasaka, Toru; Shibasaki, Hiromi; Kasuya, Yasuji; Kawashima, Soko; Yamada, Akira; Furuta, Takashi

    2012-10-01

    Factors that give rise to a large variation in the urinary ratio of free cortisone to cortisol (UFE/UFF) were investigated to accurately estimate 11β-hydroxysteroid dehydrogenase 2 (11β-HSD2) activity in humans in vivo. A water loading test was first carried out in two healthy subjects to examine the effect of water intake or urine volume on the urinary ratio of free cortisone to cortisol (UFE/UFF). The ratio was found to increase by water loading. We also examined urinary concentrations and amounts of cortisol, cortisone, creatinine, Na(+), K(+), and Cl(-), and urine volume, as possible factors affecting the urinary ratio (UFE/UFF), in 60 urine samples obtained from 15 healthy volunteers. Among these factors tested, the urinary concentration of cortisol was most highly correlated with the UFE/UFF ratio (r=-0.858), indicating that the in vivo activity of 11β-HSD2 (UFE/UFF) should fluctuate with the changes of the urinary concentration of cortisol. Based on the findings, we proposed a new estimation method of in vivo activity of 11β-HSD2 in humans, using the UFE/UFF ratio correlated with the urinary concentration of cortisol (UFE/UFF-cortisol concentration). Taking into consideration the intra-individual variabilities in the urinary concentration of cortisol, there were no significant within-day variations in 11β-HSD2 activity. The findings indicate that 11β-HSD2 activities can be accurately evaluated by simply measuring free cortisol and cortisone concentrations in spot urine samples. Furthermore, administrations of glycyrrhetinic acid in three healthy volunteers were performed to confirm the usefulness of the present assessment for the activity of 11β-HSD2. Copyright © 2012 Elsevier Inc. All rights reserved.

  16. Cortisone induces insulin resistance in C2C12 myotubes through activation of 11beta-hydroxysteroid dehydrogenase 1 and autocrinal regulation.

    Science.gov (United States)

    Park, Seung Yeon; Bae, Ji Hyun; Cho, Young Sik

    2014-04-01

    The enzyme 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) is known to catalyse inactive glucocorticoids into active forms, and its dysregulation in adipose and muscle tissues has been implicated in the development of metabolic syndrome. To delineate the molecular mechanism by which active cortisol has an antagonizing effect against insulin, we optimized the metabolic production of cortisol and its biological functions in myotubes (C2C12). Myotubes supplemented with cortisone actively catalysed its conversion into cortisol, which in turn abolished phosphorylation of Akt in response to insulin treatment. This led to diminished uptake of insulin-induced glucose. This was corroborated by the application of 11β-HSD1 inhibitor glycyrrhetinic acid and a glucocorticoid receptor antagonist RU-486, which reversed completely the antagonizing effects of cortisol on insulin action. Therefore, development of specific inhibitors targeting 11β-HSD1 might be a promising way to improve impaired insulin-stimulated glucose uptake. Copyright © 2013 John Wiley & Sons, Ltd.

  17. Simultaneous quantification of 17α-OH progesterone, 11-deoxycortisol, Δ4-androstenedione, cortisol and cortisone in newborn blood spots using liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Magnisali, P; Chalioti, M-B; Livadara, T; Mataragas, M; Paliatsiou, S; Malamitsi-Puchner, A; Moutsatsou, P

    2011-06-01

    Adrenal steroid profiling, including 17α-OH progesterone (17OHP), 11-deoxycortisol (S), Δ4-androstenedione (Δ4-A) and cortisol (F) in blood spots by tandem mass spectrometry, is used for newborn screening to detect congenital adrenal hyperplasia (CAH). Pre-analytical sample processing is critical for assay specificity and accuracy; however, it is laborious and time-consuming. This study describes the development and validation of a new Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) method for the simultaneous quantification of five steroids: 17OHP, S, Δ4-A, F and cortisone (E) in blood spots from newborns. Whole blood was eluted from a 5.00 mm dried blood spot by an aqueous solution containing the deuterium-labeled internal standards d8-17OHP and d4-cortisol. The steroids extracted from blood spot into aqueous solution were subsequently purified via Extelut mini NT1 column using diethylether. The extracts were evaporated and quantified using LC-MS/MS. The detection limit was 0.25 ng/mL for 17OHP and S, 0.4 ng/mL for Δ4-A and 0.5 ng/mL for F and E. The limit of quantification was 0.5 ng/mL for 17OHP, S and Δ4-A and 1 ng/mL for F and E. Precision for 17OHP, S, Δ4-A at concentrations of 0.5, 2, and 8 ng/mL (n=5) in fortified steroid free serum samples was 1.3-3.5% (intra-assay CV) and 7-14.8% (inter-assay CV). Precision for F and E at concentrations of 5 and 20 ng/mL was 1.5-4.8% (intra-assay, CV%) and 6-15% (inter-assay, CV%). Accuracy was calculated at concentrations of 0.5, 2, and 8 ng/mL for 17OHP, S and Δ4-A and ranged from -0.3 to 0.2%, while for F and E it ranged from -3.2 to 0.2%. Relative recoveries at concentration 2 ng/mL and 8 ng/mL for 17OHP, S, Δ4-A and at 5 ng/mL and 20 ng/mL for F and E ranged from 55% to 80%. Reference intervals were estimated for all steroids in newborns (on day 3). The steroid profile assay herein described is sensitive, specific and accurate and involves a simple pre-analytical sample manipulation; it is

  18. Determination of free cortisol and free cortisone in human urine by on-line turbulent flow chromatography coupled to fused-core chromatography-tandem mass spectrometry (TFC-HPLC-MS/MS).

    Science.gov (United States)

    Sánchez-Guijo, Alberto; Hartmann, Michaela F; Shi, Lijie; Remer, Thomas; Wudy, Stefan A

    2014-01-01

    Urinary free cortisol and urinary free cortisone are decisive markers for the diagnosis of syndromes related to the dysfunction of the adrenal gland or to evaluate certain enzymatic disorders. Here, we present a new method, designed for routine laboratory use, which enables quick determination of these analytes with minor sample workup. Turbulent flow chromatography shortens sample preparation, and connection to a fused-core particle-packed column (rugged amide-embedded C18 phase) permits a rapid and effective separation of the analytes, as well as additional separation from other related and isobaric compounds present in urine. Urinary isobaric compounds were successfully identified. The method requires only 100 μl of urine supernatant per sample. The total time between injections is 9.5 min. The solvents used for both turbulent and analytical chromatography are water and methanol, and the relatively low flows needed during the method resulted in an extended life of the columns. Linearity showed a R (2) > 0.994. Limit of detection and limit of quantification are 0.5 and 1.0 ng/ml for cortisone and 1.0 and 2.0 ng/ml for cortisol. Recoveries ranged from 99.7 to 109.1 % for cortisone and from 98.7 to 102.9 % for cortisol. Accuracy values (relative errors) for intra- and inter-assay experiments were always below 8 %, whereas precision (percent CV) ranged from 3.7 to 10.7 %. No matrix effects were detected during the validation process. The reproducibility for each analyte's retention time was excellent, with a coefficient of variation always below 0.2 %. The final validation step included the study of urine samples from healthy children and from children previously diagnosed with corticoidal disorders. The high selectivity achieved enables quick data handling.

  19. The association between perceived emotional support, maternal mood, salivary cortisol, salivary cortisone, and the ratio between the two compounds in response to acute stress in second trimester pregnant women.

    Science.gov (United States)

    La Marca-Ghaemmaghami, Pearl; La Marca, Roberto; Dainese, Sara M; Haller, Marina; Zimmermann, Roland; Ehlert, Ulrike

    2013-10-01

    Little is known about the effect of social support on the reactivity of the hypothalamic-pituitary-adrenal (HPA) axis during pregnancy. Moreover, when investigating the HPA axis most studies do not consider the activity of 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), an enzyme within the salivary glands that inactivates cortisol to cortisone. This study explores the association between perceived emotional support and the maternal psychobiological stress response to a standardized naturalistic stressor by assessing maternal mood and the reactivity of salivary cortisol (SalF), salivary cortisone (SalE), and the SalE/(E+F) ratio as a marker of 11β-HSD2 activity. Repeated saliva samples and measures of maternal mood were obtained from 34 healthy second trimester pregnant women undergoing amniocentesis which served as a psychological stressor. The pregnant women additionally responded to a questionnaire of perceived emotional support and provided sociodemographic (e.g., maternal educational degree) and pregnancy-specific data (e.g., planned versus unplanned pregnancy). Perceived emotional support neither showed a significant effect on mood nor on the SalF or SalE response to stress. However, a moderately strong positive association was found between perceived emotional support and SalE/(E+F) (r=.49). Additionally, the final regression analysis revealed a significant negative relationship between educational degree, planned/unplanned pregnancy and SalE/(E+F). Findings suggest a higher metabolization of cortisol to cortisone in pregnant women with higher emotional support. In contrast, higher maternal education and unplanned pregnancy appear to be associated with decreased salivary 11β-HSD2 activity. The current study emphasizes the importance of taking the activity of 11β-HSD2 into account when examining SalF. © 2013.

  20. High-throughput determination of cortisol, cortisone, and melatonin in oral fluid by on-line turbulent flow liquid chromatography interfaced with liquid chromatography/tandem mass spectrometry.

    Science.gov (United States)

    Fustinoni, Silvia; Polledri, Elisa; Mercadante, Rosa

    2013-07-15

    Cortisol, cortisone, and melatonin (CORTol, CORTone, and MELA, respectively) are hormones related to stress and sleep disorders. Their detection is relevant to epidemiological studies aimed at investigating the effects of circadian cycle disruption. The aim of this study was to develop and evaluate a high-throughput assay for the detection of CORTol, CORTone, and MELA concentrations in non-invasively collected oral fluid samples. A liquid chromatography/tandem mass spectrometry (LC/MS/MS) method to measure levels of CORTol, CORTone, and MELA in oral fluid samples in the presence of deuterated analogs was optimized and validated. A 50 μL aliquot of oral fluid sample, obtained by centrifugation of a chewed swab, was purified using on-line turbulent flow liquid chromatography. Analytes were then separated using C18 reversed-phase chromatography, subjected to positive ionization using an electrospray source, then quantitated using a triple quadrupole mass detector in the selected reaction monitoring mode. Limits of quantification and linear dynamic ranges were found to be 0.55 nmol/L, 5.5 nmol/L, and 0.004 nmol/L, and up to 28 nmol/L, 277 nmol/L, and 0.43 nmol/L for CORTol, CORTone, and MELA, respectively. Inter- and intra-run precisions as relative standard deviation values were <5%, and accuracies were within 95-106% of theoretical concentrations. An evaluation of matrix effects showed that the use of deuterated analogs controlled sources of bias. Furthermore, the total analysis time per sample was 13 min, resulting in a throughput of approximately 100 samples/day. To our knowledge, this is the first automated, high-throughput assay for the simultaneous quantification of CORTol, CORTone, and MELA in oral fluid specimens. Copyright © 2013 John Wiley & Sons, Ltd.

  1. Early morning salivary cortisol and cortisone, and adrenal responses to a simplified low-dose short Synacthen test in children with asthma.

    Science.gov (United States)

    Blair, Joanne; Lancaster, Gillian; Titman, Andrew; Peak, Matthew; Newlands, Paul; Collingwood, Catherine; Chesters, Christine; Moorcroft, Teresa; Wallin, Naomi; Hawcutt, Daniel; Gardner, Christopher; Didi, Mohammed; Lacy, David; Couriel, Jonathan

    2014-03-01

    To examine serum cortisol responses to a simplified low-dose short Synacthen test (LDSST) in children treated with inhaled corticosteroids (ICS) for asthma and to compare these to early morning salivary cortisol (EMSC) and cortisone (EMSCn) levels. Early morning salivary cortisol and EMSCn samples were collected for three consecutive days. On day three, Synacthen 500 ng/1·73 m(2) was administered intravenously. Samples were collected at 0, 15, 25, 35 min. A total of 269 subjects (160 M: 109 F), median (range) age 10·0 (5·1-15·2) years were studied. Peak cortisol in the LDSST was <500 nmol/l in 101 subjects (37·5%) and <350 nmol/l in 12 subjects (4·5%). Basal cortisol correlated with peak cortisol: r = 0·55, (95% CI: 0·46, 0·63, P < 0·0001). Time at which peak cortisol concentration was achieved was significantly related to the value of peak cortisol (P < 0·0001), with higher cortisol peaks occurring later in the test and lower cortisol peaks occurring earlier. EMSC and EMSCn had no predictive value for the identification of patients with a peak cortisol <500 nmol/l. EMSCn was superior to EMSC in identifying patients with a peak cortisol <350 nmol/l: a minimum EMSCn cut-off value of 12·5 nmol/l gave a negative predictive value of 99·2% and positive predictive value of 30·1%. Our data illustrate that basal measures of cortisol are likely to be of value in screening populations for patients at greatest risk of adrenal crisis. EMSCn shows promise as a screening tool for the identification of patients with severe adrenal insufficiency. © 2013 John Wiley & Sons Ltd.

  2. A simple LC-MS/MS method for the determination of cortisol, cortisone and tetrahydro-metabolites in human urine: assay development, validation and application in depression patients.

    Science.gov (United States)

    Zhai, Xuejia; Chen, Fen; Zhu, Chaoran; Lu, Yongning

    2015-03-25

    Chronic stress as well as major depressive disorders is associated with cortisol metabolism. Two enzymes modulate cortisol (F) and cortisone (E) interconversion: 11β-hydroxysteroid dehydrogenase type 1 and type 2 (11β-HSD1 and 11β-HSD2). Furthermore, F and E were inactivated by 5α and 5β reductases to their tetrahydro-metabolites: tetrahydrocortisol (THF), allo-tetrahydrocortisol (5α-THF) and tetrahydrocortisone (THE). To better understand depression a LC-MS/MS method for simultaneous determination of F, E THF, 5α-THF and THE in human urine has been developed and validated. The quantification range was 0.1-160 ng mL(-1) for F and E, and 0.2-160 ng mL(-1) for the tetrahydro-metabolites, with >86.1% recovery for all analytes. The nocturnal urine concentrations of F, E and tetrahydro-metabolites in 12 apparently healthy male adult volunteers and 12 drug-free male patients (age range, 20-50 years) with a diagnosis of depression were analyzed. A series of significant changes in glucocorticoid metabolism can be detected: F/E ratios and (THF+5α-THF)/THE ratios as well as F and THF concentrations were significantly higher in depression patients than in healthy subjects (p<0.05); 5α-THF/F ratios, 5α-THF/THF ratios as well as 5α-THF concentrations were significantly lower in depression patients (p<0.05). The results pointed to the decreased 11β-HSD2 activity and a dysfunction in the 5α-reductase pathway in depressed patients. This method allows the assessment of 11β-HSD1/2 and 5α/β-reductase activities in a single analytical run providing an innovative tool to explain the potential etiology of depression. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Longitudinal studies of plasma aldosterone, corticosterone, deoxycorticosterone, progesterone, 17-hydroxyprogesterone, cortisol, and cortisone determined simultaneously in mother and child at birth and during the early neonatal period. I. Spontaneous delivery.

    Science.gov (United States)

    Sippell, W G; Becker, H; Versmold, H T; Bidlingmaier, F; Knorr, D

    1978-06-01

    In order to obtain the still lacking reference data of individual plasma steroids in the immediate postnatal period needed for the assessment of adrenocortical function in various neonatal maladaptation syndromes, aldosterone (A), corticosterone, deoxycorticosterone (DOC), progesterone (P), 17-hydroxyprogesterone (17-OHP), cortisol, and cortisone were simultaneously followed in the same human newborn in a single 250-500 microliters peripheral plasma sample obtained at constant times during the first week of life using a mechanized Sephadex LH-20 multicolumn chromatography and standardized RIAs. Mean concentrations in 12 spontaneously delivered full term newborns of either sex and in paired umbilical (UV) and peripheral maternal (MV) venous plasma are given in the table. Besides significant maternoumbilical gradients in each steroid, DOC, P, 17-OHP, and cortisone, originating predominantly from the fetoplacental unit, disappear rapidly with steadily increasing half-lives. A, corticosterone, and cortisol, however, remain elevated in comparison with later infancy, with the exception of a marked "glucocorticoid dip" in cortisol and corticosterone levels between 2 and 12 h after birth.

  4. HPLC-ESI-MS/MS assessment of the tetrahydro-metabolites of cortisol and cortisone in bovine urine: promising markers of dexamethasone and prednisolone treatment.

    Science.gov (United States)

    Chiesa, Luca; Panseri, Sara; Pavlovic, Radmila; Cannizzo, Francesca Tiziana; Biolatti, Bartolomeo; Divari, Sara; Villa, Roberto; Arioli, Francesco

    2016-07-01

    The effects of long-term administration of low doses of dexamethasone (DX) and prednisolone (PL) on the metabolism of endogenous corticosteroids were investigated in veal calves. In addition to cortisol (F) and cortisone (E), whose interconversion is regulated by 11β-hydroxysteroid dehydrogenases (11βHSDs), special attention was paid to tetrahydrocortisol (THF), allo-tetrahydrocortisol (aTHF), tetrahydrocortisone (THE) and allo-tetrahydrocortisone (aTHE), which are produced from F and E by catalytic activity of 5α and 5β-reductases. A specifically developed HPLC-ESI-MS/MS method achieved the complete chromatographic separation of two pairs of diastereoisomers (THF/aTHF and THE/aTHE), which, with appropriate mass fragmentation patterns, provided an unambiguous conformation. The method was linear (r(2) > 0.9905; 0.5-25 ng ml(-1)), with LOQQ of 0.5 ng ml(-1). Recoveries were in range 75-114%, while matrix effects were minimal. The experimental study was carried out on three groups of male Friesian veal calves: group PL (n = 6, PL acetate 15 mg day(-1) p.o. for 31 days); group DX (n = 5, 5 mg of estradiol (E2) i.m., weekly, and 0.4 mg day(-1) of DX p.o. for 31 days) and a control group (n = 8). Urine was collected before, during (twice) and at the end of treatment. During PL administration, the tetrahydro-metabolite levels decreased gradually and remained low after the suspension of treatment. DX reduced urinary THF that persisted after the treatment, while THE levels decreased during the experiment, but rebounded substantially after the DX was withdrawn. Both DX and PL significantly interfered with the production of F and E, leading to their complete depletion. Taken together, the results demonstrate the influence of DX and PL administration on 11βHSD activity and their impact on dysfunction of the 5-reductase pathway. In conclusion, profiling tetrahydro-metabolites of F and E might serve as an alternative, indirect but reliable, non

  5. Validation of an LC-MS/MS salivary assay for glucocorticoid status assessment: Evaluation of the diurnal fluctuation of cortisol and cortisone and of their association within and between serum and saliva.

    Science.gov (United States)

    Mezzullo, Marco; Fanelli, Flaminia; Fazzini, Alessia; Gambineri, Alessandra; Vicennati, Valentina; Di Dalmazi, Guido; Pelusi, Carlotta; Mazza, Roberta; Pagotto, Uberto; Pasquali, Renato

    2016-10-01

    Salivary steroid testing represents a valuable source of biological information; however, the proper measurement of low salivary levels is challenging for direct immunoassays, lacking adequate sensitivity and specificity and causing poor inter-laboratory reproducibility. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) has overcome previous analytical limits, often providing results deviating from previous knowledge. Nowadays, LC-MS/MS is being introduced in clinical laboratories for salivary cortisol testing; however, so far only a few studies have reported thorough biological validation based on LC-MS/MS data. In this study, we provide a thorough analytical, pre-analytical and biological validation of an LC-MS/MS method for the measurement of salivary cortisol (F) and of its inactive metabolite cortisone (E). Analytes were extracted from 50μl of saliva, were then separated in 7.5min LC-gradient and detected by negative electrospray ionization-multiple reaction monitoring. The reliability of a widely diffused collection device, Salivette(®), was assessed and the overall procedure was validated. The diurnal cortisol and cortisone fluctuation in saliva and serum was described by a four paired collection protocol (8 am, 12 am, 4 pm and 8 pm) in 19 healthy subjects. The assay allowed the quantitation of F and E down to 39.1 and 78.1pg/ml, with an imprecision range of 5.5-9.5%, 3.9-14.1% and 2.6-14.4%, and an accuracy range of 105.5-113.1%, 88.5-98.7% and 90.7-96.7% for both analytes at low, medium and high levels, respectively. Salivette(®) provided comparable results and better precision (CVcortisone, with values lowering from the morning to the evening time points (Pcortisone. The simultaneous determination of both hormones in saliva allowed the differential estimation of the active and of the total glucocorticoid exposure over the daytime. The assay could provide further insight into the comprehension of normal and dysfunctional glucocorticoid circadian

  6. Novel 11β-hydroxysteroid dehydrogenase 1 inhibitors reduce cortisol levels in keratinocytes and improve dermal collagen content in human ex vivo skin after exposure to cortisone and UV.

    Science.gov (United States)

    Boudon, Stéphanie M; Vuorinen, Anna; Geotti-Bianchini, Piero; Wandeler, Eliane; Kratschmar, Denise V; Heidl, Marc; Campiche, Remo; Jackson, Eileen; Odermatt, Alex

    2017-01-01

    Activity and selectivity assessment of new bi-aryl amide 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) inhibitors, prepared in a modular manner via Suzuki cross-coupling, are described. Several compounds inhibiting 11β-HSD1 at nanomolar concentrations were identified. Compounds 2b, 3e, 7b and 12e were shown to selectively inhibit 11β-HSD1 over 11β-HSD2, 17β-HSD1 and 17β-HSD2. These inhibitors also potently inhibited 11β-HSD1 activity in intact HEK-293 cells expressing the recombinant enzyme and in intact primary human keratinocytes expressing endogenous 11β-HSD1. Moreover, compounds 2b, 3e and 12e were tested for their activity in human skin biopsies. They were able to prevent, at least in part, both the cortisone- and the UV-mediated decreases in collagen content. Thus, inhibition of 11β-HSD1 by these compounds can be further investigated to delay or prevent UV-mediated skin damage and skin aging.

  7. The diagnostic performance of urinary free cortisol is better than the cortisol:cortisone ratio in detecting de novo Cushing's syndrome: the use of a LC-MS/MS method in routine clinical practice.

    Science.gov (United States)

    Ceccato, Filippo; Antonelli, Giorgia; Barbot, Mattia; Zilio, Marialuisa; Mazzai, Linda; Gatti, Rosalba; Zaninotto, Martina; Mantero, Franco; Boscaro, Marco; Plebani, Mario; Scaroni, Carla

    2014-07-01

    The Endocrine Society Clinical Guidelines recommend measuring 24-h urinary free cortisol (UFF) levels using a highly accurate method as one of the first-line screening tests for the diagnosis of Cushing's Syndrome (CS). We evaluated the performance of UFF, urinary free cortisone (UFE), and the UFF:UFE ratio, measured using a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The LC-MS/MS was used to analyze UFF and UFE levels in 43 surgically confirmed CS patients: 26 with Cushing's disease (CD, 16 de novo and ten recurrences), 11 with adrenal CS and six with ectopic CS; 22 CD patients in remission; 14 eu-cortisolemic CD patients receiving medical therapy; 60 non-CS patients; and 70 healthy controls. Sensitivity and specificity were determined in the combined groups of non-CS patients, healthy controls, and CD in remission. UFF>170 nmol/24 h showed 98.7% specificity and 100% sensitivity for de novo CS, while sensitivity was 80% for recurrent CD patients, who were characterized by lower UFF levels. The UFF:UFE and UFF+UFE showed lower sensitivity and specificity than UFF. Ectopic CS patients had the highest UFF and UFF:UFE levels, which were normal in the CD remission patients and in those receiving medical therapy. Our data suggest high diagnostic performance of UFF excretion measured using LC-MS/MS, in detecting de novo CS. UFF:UFE and UFF+UFE assessments are not useful in the first step of CS diagnosis, although high levels were found to be indicative of ectopic CS. © 2014 European Society of Endocrinology.

  8. [Intra-articular injection of cortisone].

    Science.gov (United States)

    Hammer, M; Schwarz, T; Ganser, G

    2015-11-01

    Intra-articular injections with glucocorticoids are standard procedures according to therapy guidelines in many rheumatic conditions. There is increasing evidence from clinical trials on the treatment of rheumatoid arthritis that more patients will attain the target of remission using a combination of systemic medication and intra-articular injections with glucocorticoids compared to systemic medication alone. Intra-articular injections with glucocorticoids play an important role in the therapeutic management of pediatric rheumatic diseases. In many countries competency in performing intra-articular injections is among the important skills necessary for certification as a specialist in rheumatology.

  9. [Pharmacogenic osteoporosis beyond cortisone. Proton pump inhibitors, glitazones and diuretics].

    Science.gov (United States)

    Kann, P H; Hadji, P; Bergmann, R S

    2014-05-01

    [corrected] There are many drugs which can cause osteoporosis or at least favor its initiation. The effect of hormones and drugs with antihormonal activity, such as glucocorticoids and aromatase inhibitors, on initiation of osteoporosis is well known. In addition, proton pump inhibitors, glitazones and diuretics also influence the formation of osteoporosis. The results of currently available studies on the correlation between proton pump inhibitors, glitazones and diuretics on formation of osteoporosis were evaluated and summarized. Proton pump inhibitors and glitazones increase the risk for osteoporotic fractures. Loop diuretics may slightly increase fracture risk, whereas thiazides were shown to be osteoprotective by reducing fracture probability on a relevant scale. Proton pump inhibitors should not be prescribed without serious consideration and then only as long as necessary. Alternatively, the administration of the less effective H2 antagonists should be considered when possible due to the reduction of acid secretion. Because the long-term intake of thiazides is associated with a clinically relevant reduction in the risk of fractures and they are economic and well-tolerated, prescription can be thoroughly recommended within the framework of differential diagnostic considerations in an appropriate clinical context. The briefly increased risk of falling immediately after starting diuretic therapy is the only point which needs to be considered.

  10. Contrast examination as a prognostic factor in the treatment of solitary bone cyst by cortisone injection

    Energy Technology Data Exchange (ETDEWEB)

    Capanna, R.; Campanacci, M.; Albisinni, U.; Caroli, G.C.

    1984-07-01

    Local injection of radiopaque medium demonstrated the presence of intracystic fibrous septa in 13 patients with solitary bone cyst. Contrast examination was helpful in predicting the response of solitary bone cysts to treatment by injection of methylprednisolone-acetate (MPA). As the number of septa increased, an increased difficulty in obtaining an equal distribution of MPA inside the cyst and a higher incidence of incomplete healing of the cyst was encountered.

  11. Conservation of apoptosis as an immune regulatory mechanism: effects of cortisol and cortisone on carp lymphocytes.

    NARCIS (Netherlands)

    Weyts, F.A.A.; Verburg-van Kemenade, B.M.L.; Flik, G.; Lambert, J.G.D.; Wendelaar Bonga, S.E.

    1997-01-01

    This is the first study to show that apoptosis as an immune regulatory mechanism is conserved in fish, demonstrating its importance in maintaining immunological homeostasis. The data further show that this mechanism is subject to control by glucocorticosteroids. Carp plasma cortisol concentrations

  12. Conservation of apoptosis as an immune regulatory mechanism: effects of cortisol and cortisone on carp lymphocytes.

    NARCIS (Netherlands)

    Weyts, F.A.A.; Verburg-van Kemenade, B.M.L.; Flik, G.; Lambert, J.G.D.; Wendelaar Bonga, S.E.

    1997-01-01

    This is the first study to show that apoptosis as an immune regulatory mechanism is conserved in fish, demonstrating its importance in maintaining immunological homeostasis. The data further show that this mechanism is subject to control by glucocorticosteroids. Carp plasma cortisol concentrations i

  13. [Residual states in 30 percent of adult patients with Bell's palsy. Early treatment with cortisone improves the healing process].

    Science.gov (United States)

    Berg, Thomas; Stjernquist-Desatnik, Anna; Kanerva, Mervi; Hultcrantz, Malou; Engström, Mats; Jonsson, Lars

    2015-01-06

    Bell's palsy is an acute unilateral weakness or paralysis of the face of unknown cause. The incidence of the disease is 30 individuals per 100,000 per year. It is a diagnosis of exclusion and other known causes for acute peripheral facial palsy must be ruled out. The prognosis is overall favorable and about 70% of the patients recover completely within 6 months without treatment. Recent randomized controlled Bell's palsy trials have shown that treatment with corticosteroids shortens time to recovery and improves recovery rates while antiviral treatment alone is not more effective than placebo. The combination of corticosteroids and antivirals has not been proven more effective than corticosteroids alone. We present an update of Bell's palsy in adults with focus on diagnosis, treatment and follow-up of these patients.

  14. Tandem mass spectrometry determined maternal cortisone to cortisol ratio and psychiatric morbidity during pregnancy-interaction with birth weight

    NARCIS (Netherlands)

    Hellgren, Charlotte; Edvinsson, Åsa; Olivier, Jocelien D; Fornes, Romina; Stener-Victorin, Elisabet; Ubhayasekera, S J Kumari A; Skalkidou, Alkistis; Bergquist, Jonas; Sundström-Poromaa, Inger

    2016-01-01

    Maternal serum cortisol has been suggested to be influenced by psychiatric morbidity, and may also influence fetal growth. However, several studies found equal cortisol levels in depressed and healthy pregnant women. Placental 11-β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) shields the fetus

  15. Effect of immunosuppressive and other drugs on the cortisol-cortisone shuttle in human kidney and liver.

    Science.gov (United States)

    Quinkler, M; Jussli, J; Bähr, V; Pfeiffer, A F H; Lepenies, J; Diederich, S

    2007-08-01

    Impaired 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) has been suggested in patients with hypertension or renal disease, where it may contribute to sodium retention and hypertension. 11beta-HSD1, which is expressed predominantly in liver and adipose tissue, influences glucose homeostasis and fat distribution by altering intracellular cortisol (F) concentrations. We tested immunosuppressive drugs that cause hypertension, and substances that interfere with steroidogenesis or influence glucose homeostasis for their ability to influence the inhibition of 11beta-HSD isozymes. For inhibition experiments, we used microsomes prepared from unaffected parts of human liver segments and resected human kidney cortex because of hepatocarcinoma or renal cell cancer. The inhibitory potency of several compounds was evaluated in concentrations from 10(-9)-10(-5) mol/l. Only sirolimus, but not cyclosporine A, tacrolimus, mycophenolate mofetil, or azathioprine showed a slight inhibition of 11beta-HSD2 activity. None of the drugs that inhibit steroidogenesis (suramine, mitotane, etomidate, and aminogluthethimide) or steroid metabolism (rifampicine) influenced 11beta-HSDs, nor did ginsenoides Re, Rc, and Rb1. Among sulfonylureas, only gliclazide decreased significantly 11beta-HSD1 activity. Increased blood pressure due to immunosuppressive drugs is probably not caused by direct inhibition of 11beta-HSD2. An additional glucose lowering effect of sulfonylurea gliclazide may be due to its ability to inhibit 11beta-HSD1.

  16. Suitability of bovine bile compared to urine for detection of free, sulfate and glucuronate boldenone, androstadienedione, cortisol, cortisone, prednisolone, prednisone and dexamethasone by LC-MS/MS.

    Science.gov (United States)

    Chiesa, Luca; Nobile, Maria; Panseri, Sara; Vigo, Daniele; Pavlovic, Radmila; Arioli, Francesco

    2015-12-01

    The administration of boldenone and androstadienedione to cattle is forbidden in the European Union, while prednisolone is permitted for therapeutic purposes. They are pseudoendogenous substances (endogenously produced under certain circumstances). The commonly used matrices in control analyses are urine or liver. With the aim of improving the residue controls, we previously validated a method for steroid analysis in bile. We now compare urine (a 'classic' matrix) to bile, both collected at the slaughterhouse, to understand whether the detection of steroids in the latter is easier. With the aim of having clearer results, we tested the presence of the synthetic corticosteroid dexamethasone. The results show that bile does not substantially improve the detection of boldenone, or its conjugates, prednisolone and prednisone. Dexamethasone, instead, was found in 10 out of 53 bovine bile samples, but only in one urine sample from the same animals. Bile could constitute a novel matrix for the analysis of residues in food-producing animals, and possibly not only of synthetic corticosteroids. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Detection of boldenone, its sulfate and glucuronate forms, androstadienedione, cortisol, cortisone, prednisolone, prednisone and dexamethasone in bovine bile and urine by LC-MS/MS: preliminary results.

    Directory of Open Access Journals (Sweden)

    Maria Nobile

    2015-07-01

    Full Text Available The European Union regulations ban or regulate the use of substances with hormonal action. There are, however, some detectable steroids in biological matrices from cattle to which no administration were made. These are the so called “grey-zone” or “pseudoendogenous” substances (endogenously produced under certain circumstances. The administration of boldenone and androstadienedione to cattle is forbidden both for therapeutic or growth promotion purposes, while therapeutic use of prednisolone is permitted. The control of the use of these substances is hampered by their pseudoendogenous nature. We made a comparison between analyses performed on the classical matrix urine with bile (a novel matrix from the same animals, with the aim to determine the better matrix for the above mentioned steroids. We tested the synthetic corticosteroid dexamethasone, too. The preliminary results do not show any difference between the two matrices, as concern the pseudoendogenous substances. The data about dexamethasone were instead very promising about the use of bile. The detection frequency and concentration levels were, in fact, higher in bile than in urine from the same animals.

  18. Quantitative indicator of cortisone in human adrenal tissue as a criterion for determining the duration of the duration of fatal injury

    Directory of Open Access Journals (Sweden)

    Shkand T.V.

    2013-01-01

    Full Text Available To elucidate pathogenetic mechanisms of myocardium necrosis, to develop the preventive and treatment measures its experimental studying in different models is necessary. The paper covers the dynamics of morphological changes in myocardium after cryoeffect in heart for 15 and 30 sec, ligation of left coronary artery and introduction of adrenalin toxic doses. It has been established that cryoeffect to heart led to the appearance of necrotic zone in myocardium with no ischemic inflammation phase, herewith the depth of cardiac muscle lesion depended directly on cryoeffect duration. The ligation of coronary artery contributed to the formation of ischemic necrosis of myocardium in the zone of ligated vessel basin with manifested discirculatory disorders. Focus lesion of myocardium resulted from the introduction of toxic doses of adrenalin was focused around arterial vessels, which later led to periarterial proliferation of fibroblasts and formation of granulation tissue.

  19. 11β-Hydroxysteroid Dehydrogenase Activity in the Brain Does Not Contribute to Systemic Interconversion of Cortisol and Cortisone in Healthy Men

    OpenAIRE

    Kilgour, Alixe H M; Semple, Scott; Marshall, Ian; Andrews, Peter; Andrew, Ruth; Walker, Brian R.

    2015-01-01

    Context and Objective: 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) catalyses regeneration of cortisol in liver, adipose tissue, and skeletal muscle, making a substantial contribution to circulating cortisol as demonstrated in humans by combining stable isotope tracer infusion with arteriovenous sampling. In the brain, 11βHSD1 is a potential therapeutic target implicated in age-associated cognitive dysfunction. We aimed to quantify brain 11βHSD1 activity, both to assess its contribution ...

  20. NEEDS OF THE MIDDLE EAST FOR HEALTH MANPOWER

    Directory of Open Access Journals (Sweden)

    G. Saroukhanian

    1968-01-01

    Full Text Available The effect of cortisone on the experimental gastric ulceration produced by intraperitoneal injection of aspirin in the rat is studied. Cortisone has significantly prevented the appearance of aspirin_ induced gastric ulceration. The possible mechanism of this effect of cortisone is discussed.

  1. Novel 11β-hydroxysteroid dehydrogenase 1 inhibitors reduce cortisol levels in keratinocytes and improve dermal collagen content in human ex vivo skin after exposure to cortisone and UV

    OpenAIRE

    Boudon, Stéphanie M.; Vuorinen, Anna; Geotti-Bianchini, Piero; Wandeler, Eliane; Kratschmar, Denise V.; Heidl, Marc; Campiche, Remo; Jackson, Eileen; Odermatt, Alex

    2017-01-01

    Activity and selectivity assessment of new bi-aryl amide 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) inhibitors, prepared in a modular manner via Suzuki cross-coupling, are described. Several compounds inhibiting 11β-HSD1 at nanomolar concentrations were identified. Compounds 2b, 3e, 7b and 12e were shown to selectively inhibit 11β-HSD1 over 11β-HSD2, 17β-HSD1 and 17β-HSD2. These inhibitors also potently inhibited 11β-HSD1 activity in intact HEK-293 cells expressing the recombinant enzyme a...

  2. The clinlcal control observation between Pingyangmycin and cortisone treatment in infants and children cavernous hemangioma%强地松与平阳霉素治疗血管瘤的对照观察

    Institute of Scientific and Technical Information of China (English)

    王涛; 孙劲东; 郑长泰; 廖天安

    2003-01-01

    目的评价强地松与平阳霉素及鱼油酸钠治疗要幼儿海绵状血管瘤的疗效.方法用口服强地松与平阳霉素瘤腔内注射分别治疗颌面部海绵状血管瘤共102例.随访6个月~1年.采用卡方检验处理资料.结果强地松治疗组治愈率41%,总有效率63%.平阳霉素组患者治愈率75%,总有效率86%.结论两种方法中,平阳霉素瘤腔内注射治疗要幼儿颌面部海绵状血管瘤的效果最佳,并且并发症低、副作用小.可作为临床首选治疗方案.

  3. Cortisol metabolism after weight loss- associations with 11 β-HSD type 1 and markers of obesity in women

    DEFF Research Database (Denmark)

    Rask, Erling; Simonyte, K; Lönn, L

    2013-01-01

    excretion, body composition including regional adipose tissue depots and insulin resistance by HOMA-IR before and two years after gastric bypass surgery. Results:  After weight loss excretion of cortisol and cortisone metabolites decreased. Both cortisol and cortisone metabolite excretion correlated...... to central obesity, where the intraabdominal fat depot showed the strongest association. Cortisol metabolites correlated with 11β-HSD type 1-activity in abdominal subcutaneous adipose tissue. The ratio of cortisol to cortisone metabolites [(5α-tetrahydrocortisol (5αTHF) + tetrahydrocortisol (THF)+ α...

  4. Analysis of the Glucocorticoid Receptor in Spontaneous and Drug-induced Steroid Resistant Mutants Isolated from the Human Leukemic Cell Line CEM-C7

    Science.gov (United States)

    1991-01-04

    lOx SSC (1.5 M NaCl, 0,15 M sodium citrate, pH 7.0) overnight and crosslinked for 2 min under the UV lamp in the tissue culture hood. The Nytran...Tris pH 7.4, 1.5 M NaCl), and the DNA was transfered to Nytran filters using 20X SSC. The filters were cross-linked for 30 sec under the UV light in...Response to cortisone and development of cortisone resistance in a cortisone -sensitive lymphosarcoma of the mouse. J. Natl. Cancer Inst. 20.: 1091-1109

  5. Further Enrichment and Analysis of Rat CFU-s

    Science.gov (United States)

    1990-01-01

    argon laser was tuned to the UV and was used to excite the DAPI-DNA complex. By gating on the APC- Ox720 and PhyB-x22- cells, a new FITC-W3/13...Thy-I and light scatter properties of CFU-s from cortisone pre-treated rats. The cortisone treatment diminished marrow lymphocytes and separated them...from cortisone - resistant CFU-s. Starting with marrow from normal rats, Goldschneider et al. Further Enrichment and Analysis of Rat CFU-s 190 A

  6. [Clinical single case study (n-of-1 trial)].

    Science.gov (United States)

    Speich, R

    1998-09-01

    We conducted a single case (N-of-1) randomized trial in two patients. In the first case with bronchiolitis obliterans after lung transplantation a beneficial effect of inhaled steroids could be documented. The second patient suffered from symptoms compatible with HIV-associated M. Addison improving after cortisone, but the adrenocortical function was normal. Because the patient required the cortison treatment to be continued, we performed a n-of-1 trial which demonstrated the inefficacy of cortisone. This experience underscores the feasibility and usefulness of N-of-1 randomized clinical trials in medical practice.

  7. 地氟醚对手术病人肾素-血管紧张素-醛固酮系统及皮质醇的影响%The effects of desflurane on renin-angiotension-aldosterone system and plasma cortisone concentration in surgical patients

    Institute of Scientific and Technical Information of China (English)

    石莉; 鲍红光; 杨海基; 王天元

    2001-01-01

    目的观察地氟醚在手术中对肾素-血管紧张素-醛固酮系统(RAAS)及皮质醇的影响.方法选择30例择期在全麻下实施上腹部手术病人,随机分为地氟醚组和安氟醚组,每组15例.术中分五个时点采集静脉血,以放免法测定血浆肾素活性(PRA)、血管紧张素Ⅱ(AⅡ)、醛固酮(Al)及皮质醇(Cor).结果地氟醚组在切皮时即出现PRA、AⅡ、Al的升高,尤以Al显著,术中继续升高.两组Cor术中均升高,但无明显组间差异.地氟醚组术中血压及心率增加明显.结论地氟醚可早期激活RAAS,并有交感兴奋作用;但不能抑制手术刺激引起的Cor升高.

  8. Sunburn

    Science.gov (United States)

    ... from sunburn. DO NOT give aspirin to children. Cortisone creams may help reduce the inflammation. Loose cotton ... m. and 4 p.m. Wear sunglasses with UV protection. When to Contact a Medical Professional Call ...

  9. Atopic dermatitis - children - homecare

    Science.gov (United States)

    ... medicines: The provider will probably prescribe a mild cortisone (steroid) cream or ointment at first. Topical steroids ... your child's skin is carefully exposed to ultraviolet (UV) light Short-term use of systemic steroids (steroids ...

  10. Cicatricial Pemphigoid

    Science.gov (United States)

    ... several ways to treat pemphigoid, including tetracycline with niacinamide, cortisone-type drugs that suppress the immune reaction, ... Another alternative is the use of tetracycline and niacinamide, taking one capsule of each, four times daily. ...

  11. Disease: H00259 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available mal enzyme complex responsible for the interconversion of cortisol and cortisone. Endocrine disease; Metab...olic disease hsa00140(3291) Steroid hormone biosynthesis HSD11B2 [HSA:3291] [KO:K00

  12. FOURNIER'S GANGRENE COMPLICATING VASECTOMY V.M. ...

    African Journals Online (AJOL)

    hi-tech

    2003-09-09

    Sep 9, 2003 ... The possible operational factors for the complications are explored and preventive ..... trauma, malignancy, malnutrition, renal failure, cortisone therapy, lupus ... second one depended on exogenous testosterone for "normal".

  13. Detection and distribution of endogenous steroids in human stratum corneum

    Directory of Open Access Journals (Sweden)

    Shu-Ping Tseng

    2014-03-01

    Conclusion: The results demonstrate that, with the achievable sensitivity of current analytical technology, physiological concentrations of endogenous steroids, such as hydrocortisone and cortisone, can be found in the SC of some individuals.

  14. A Case Study on Idiopathic Orbital Pseudotumor: Surgery and ...

    African Journals Online (AJOL)

    ... observed in all the patients. Keywords: Orbital fat, Visual acuity, Optic disk edema, Optic nerve, Cortisone therapy ... Hunt syndrome, pituitary histiocytosis, idiopathic meningitis ... computer tomography (CT) and magnetic resonance imaging ...

  15. Study on Pathogenicity of the Aspergillus species in experimentally immunosuppressed mice

    Directory of Open Access Journals (Sweden)

    Chhabra

    2008-06-01

    Full Text Available Aspergillus, a saprophytic mould, distributed widely in the environment is a frequently recognized etiological agent in a number of disease conditions especially in immunocompromised patients. Mice untreated as well as immunocompromised by administering cortisone, were inoculated intraperitoneally with spores of Aspergillus spp. The administration of cortisone rendered mice highly susceptible to fatal visceral aspergillosis. Heat killed spores produced no evident lesions in control or experimental mice. [Veterinary World 2008; 1(3.000: 69-70

  16. Teratology, survival, and reversal learning after fetal irradiation of mice by 2450-MHz microwave energy

    Energy Technology Data Exchange (ETDEWEB)

    Chernovetz, M.E. (Univ. of Tulsa, OK); Justesen, D.R.; King, N.W.; Wagner, J.E.

    1975-12-01

    Eighty primigravid mice of the C3H-HeJ strain were subjected to 2450-MHz sinusoidally modulated microwave radiation or to sham radiation (with or without an accompanying injection of 5 mg of cortisone as a teratological marker) on the 11th, 12th, 13th or 14th day of gestation. The radiation treatment consisted of a single intense dosing of microwave energy (38 mW/g for 600 sec = 22.8 J/g) in a multi-mode cavity. On the 19th day of gestation fetuses were taken via Caesarean section and were observed for gross structural abnormalities. While radiation of dams failed reliably to increase the incidence of fetal mortality or morbidity above that of controls, the dams treated with cortisone gave birth to reliably greater numbers of stillborn and deformed fetuses. During their 14th day of gestation 60 primigravid mice received the radiation or sham-radiation treatment, half with and half without the accompanying injection of cortisone. A virtually complete failure to survive to weaning characterized the pups born of the sham-radiated cortisone-treated group of dams, but the incidence of cortisone-induced mortality was reliably reduced in pups whose dams were also radiated by microwave energy. No differences in maze performances were observed in the mice as a function of their placement in the control or the radiation condition, but offspring of cortisone-treated, radiated dams made reliably more errors. Careful measurement of elevations of colonic temperatures of radiated dams shortly after treatment with cortisone revealed an averaged ..delta..T that is close to that observed in a comparably radiated volume of water of equivalent mass. If the finding has generality beyond the gravid mouse--if, that is, cortisone effectively and reversibly renders the mammal ectothermic--an important advance in biological dosimetry of non-ionizing radiation may be at hand.

  17. Glucocorticoid-mediated effects on metabolism are reversed by targeting 11 beta hydroxysteroid dehydrogenase type 1 in human skeletal muscle.

    Science.gov (United States)

    Salehzadeh, Firoozeh; Al-Khalili, Lubna; Kulkarni, Sameer S; Wang, Minghan; Lönnqvist, Fredrik; Krook, Anna

    2009-03-01

    Adipose tissue and liver play important roles in mediating the metabolic actions of glucocorticoids. However, the effects of glucocorticoids on glucose and lipid metabolism in skeletal muscle are not understood completely. Intracellular glucocorticoid action is dependent on 11 beta-hydroxysteroid dehydrogenase 1 (HSD1), an enzyme that converts cortisone to active cortisol. We investigated the direct role of HSD1 in cultured primary human skeletal muscle cells using siRNA and pharmacological inhibitors of the enzyme. Primary human skeletal muscle cells were cultured in the presence of 0.5 microM cortisone or 0.5 microM cortisol for eight days. siRNA was utilized to reduce expression of either HSD1 or pyruvate dehydrogenase kinase (PDK) 4. Effects of pharmacological inhibitors of HSD1 were also studied. Exposure to cortisone or cortisol decreased basal glucose uptake and glucose incorporation into glycogen, but was without effect on the insulin-stimulated response. Glucocorticoid exposure increased palmitate oxidation, as well as the expression of PDK4. siRNA-mediated reduction or pharmacological inhibition of HSD1 prevented the effects of cortisone, but not cortisol, on metabolic responses. siRNA-mediated reduction of PDK4 prevented the effect of cortisol to attenuate glycogen synthesis. Targeted reduction or pharmacological inhibition of HSD1 in primary human skeletal muscle cells prevents the effects of cortisone, but not cortisol, on glucose metabolism and palmitate oxidation. Furthermore, the glucocorticoid-mediated reductions in glucose metabolism are dependent on PDK4.

  18. The effect of acute bilateral adrenalectomy on vasopressor responses to catecholamines in dogs.

    Science.gov (United States)

    Chopde, C T; Brahmankar, D M; Sheorey, R V; Udhoji, A G; Dorle, A K

    1975-04-01

    The effect of acute bilateral adrenalectomy on the pressor responses to adrenaline, noradrenaline and isoprenaline was studied in anaesthetized dogs. The responses to all the three catecholamines were reduced by adrenalectomy. Treatment with cortisone, cyclic AMP partially restored the responsiveness. Desocycorticosterone, aldosterone, hydrocortisone, phenylbutazone or infusion of either saline and noradrenaline failed to improve the impaired pressor responses seen in adrenalectomized dogs. Treatment with corticosterone alone. combined administration of aldosterone and hydrocortisone or cortisone followed by cyclic 3',5'-AMP also restored catecholamine responses amost to normal. The pressor responses to catecholmaines in dogs were also reduced by metyrapone-induced cortical insufficiency. Administration of corticosterone, cortisone or cyclic AMP slightly improved these responses; the recovery was not, however, as effective as that noted in the adrenalectomized condition.

  19. 11Beta-HSD type 1 expression in human adipose tissue: impact of gender, obesity, and fat localization

    DEFF Research Database (Denmark)

    Paulsen, Søren Kildeberg; Pedersen, Steen Bønløkke; Fisker, Sanne

    2007-01-01

    OBJECTIVE: Pre-receptor amplification of glucocorticoids is, in part, determined by the isoenzymes 11beta-hydroxysteroid dehydrogenase (11beta-HSD) type 1 and type 2, interconverting inert cortisone and active cortisol. Increased tissue activity of cortisol may play a part in features of the meta......OBJECTIVE: Pre-receptor amplification of glucocorticoids is, in part, determined by the isoenzymes 11beta-hydroxysteroid dehydrogenase (11beta-HSD) type 1 and type 2, interconverting inert cortisone and active cortisol. Increased tissue activity of cortisol may play a part in features...

  20. Ginseng treatment reduces bacterial load and lung pathology in chronic Pseudomonas aeruginosa pneumonia in rats

    DEFF Research Database (Denmark)

    Song, Z; Johansen, H K; Faber, V

    1997-01-01

    the inflammation and antibody responses could be changed by treatment with the Chinese herbal medicine ginseng. An aqueous extract of ginseng was injected subcutaneously, and cortisone and saline were used as controls. Two weeks after challenge with P. aeruginosa, the ginseng-treated group showed a significantly...... against P. aeruginosa sonicate and a shift from an acute type to a chronic type of lung inflammation compared to those in the control and cortisone-treated groups were observed. These findings indicate that ginseng treatment of an experimental P. aeruginosa pneumonia in rats promotes a cellular response...

  1. MRI diagnosis of and follow-up after humoral head necrosis as complication after chemotherapy; MRT-Diagnose und Verlauf beidseitiger Humeruskopfnekrosen aus Komplikation nach Chemotherapie

    Energy Technology Data Exchange (ETDEWEB)

    Morakkabati, N. [Bonn Univ. (Germany). Radiologische Klinik; Strunk, H. [Bonn Univ. (Germany). Radiologische Klinik; Gutjahr, P. [Mainz Univ. (Germany). Kinderklinik

    1997-01-01

    A 14-year old female patient was treated with chemotherapy including cortisone for malignant T-cell lymphoma. After chemotherapy she complained of pain in both hips and shoulders. Bone scientigraphy failed to show any abnormality. However, bilateral femoral and humeral head necrosis was seen with MR imaging, which was also useful for follow up. (orig.) [Deutsch] Eine 14jaehrige Patientin wurde aufgrund eines malignen Non-Hodgkin-Lymphoms zystostatisch behandelt, unter anderem mit Cortison. Nach dieser Chemotherapie traten Schmerzen in der Huefte und in beiden Schultern auf. Skelettszintigraphie und Roentgenuebersichtsaufnahme zeigten zunaechst keinen pathologischen Befund. In der MRT konnten jedoch beidseitige Humerus- und Femurkopfnekrosen nachgewiesen sowie im Verlauf kontrolliert werden. (orig.)

  2. [Study of various factors affecting the colonization of the digestive tract in white mice by Candida albicans].

    Science.gov (United States)

    Auger, P; Joly, J

    1976-03-01

    This paper deals with the quantitative localization of Candida albicans in different parts of white micr gastrointestinal tract after oral inoculation of the yeast. Animals are previously treated with ampicillin, cortisone, or estradiol. Female pregnant and normal adult mice are also used. Our results show that the number of yeasts increases respectively in small intestine, stomach, caecum, and sigmoid. As compared with normal adult mice, C. albicans is more abundant in mice treated wtih ampicillin or cortisone whereas the yeast growth is lower in pregnant animals or in mice receiving estradiol. Moreover, male animals ordinarily show higher values than those found in female mice.

  3. Muramyl Peptide-Enhanced Sleep: Pharmacological Optimization of Performance

    Science.gov (United States)

    1991-06-01

    thymidine incorporation in mink lung epithelial cells was 0.05 ng/ml; d) the neutralizing doses50 (ND50) of antibodies against porcine (TGFP) raised in...and 10- 5 M; IFN, 1, 10, 102, and 103 U/ml; VIP, DSIP, and 5-HT, 10- 8 , 10- 7 , 10- 6 , and 10- 5 M; and hydro- cortisone , 10- 5, 10- 4 , and 10- 3...VIP. DSIP. MDP and hydro- cortisone to regulate HLAR expression Several additional substances were tested alone and in combination with IFNy to

  4. Suppression of NFkB by Tetrathiomolybdate Inhibits Tumor Angiogenesis and Enhances Apoptosis in Human Breast Cancers

    Science.gov (United States)

    2005-05-01

    deficiency, we cortisone . The HME cells were characterized as being keratin-19 positive, used a potent and novel copper chelator, TM, 4 developed for the...addition of 2 nM CuSO4 which eventually metastasize to the lungs (25). These mice develop for 72 h. Nuclear proteins were extracted, incubated with...hydro- Mice were anesthetized using 10 mg/ml ketamine, 1 mg/ml cortisone (14). xylazine, and 0.01 mg/ml glycopyrrolate, and an incision Detection of

  5. Disease: H01111 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available H01111 Cortisone reductase deficiency (CRD) Cortisone reductase deficiency (CRD) is...arity, anovulatory infertility, obesity, insulin resistance and hyperandrogenism. 11...ne biosynthesis hsa00980(3290) Metabolism of xenobiotics by cytochrome P450 H6PD [HSA:9563] [KO:K13937] HSD11...ted with heterozygous mutations in 11beta-hydroxysteroid dehydrogenase type 1. Proc Natl Acad Sci U S A 108:4111-6 (2011...M, Shackleton CH, Stewart PM Mutations in the genes encoding 11beta-hydroxysteroid dehydrogenase type 1 and

  6. Two cases of primary sclerosing cholangitis - ERCP-documentation in immunesuppressive therapy of the last 3 years

    Energy Technology Data Exchange (ETDEWEB)

    Mendel, R.; Droste, R.; Bade, J.; Hebestreit, H.P.; Georgi, M.

    1985-02-01

    X-ray characteristics of two cases of primary sclerosing cholangitis are described. A discussion of clinical, immunological and histological features of the disease and the 3-years progress of a 40 year old man during treatment with immunesuppressive therapy (Imurek at the beginning with cortisone) is shown. The arrest of the progression of the disease is supposed.

  7. Appearance and cellular distribution of lectin-like receptors for alpha 1-acid glycoprotein in the developing rat testis

    DEFF Research Database (Denmark)

    Andersen, U O; Bøg-Hansen, T C; Kirkeby, S

    1996-01-01

    glycoprotein glycoforms to their receptors is inhibited by steroids. Testosterone, oestradiol and progesterone inhibited the binding of alpha 1-acid glycoprotein glycoform A to its receptor. Cortisone, aldosterone, oestradiol and progesterone inhibited the binding of alpha 1-acid glycoprotein glycoforms B...

  8. Search for the effect of E-beam irradiation on some steroids

    Energy Technology Data Exchange (ETDEWEB)

    Marciniec, B. E-mail: bmarcin@amp.edu.pl; Ogrodowczyk, M.; Dettlaff, K

    2005-03-01

    Seven steroid derivatives (hydrocortisone, hydrocortisone acetate, prednisolone, prednisolone acetate, methylprednisolone acetate, dexamethasone and fludrocortisone acetate) irradiated in the solid phase 10 MeV electrons, were studied by chromatographic methods (TLC and HPLC). Before the irradiation the derivatives contained different amounts of the following impurities: cortisone, cortisone acetate, prednisolone, prednisolone acetate and prednisone. After irradiation with a dose of upto 200 kGy radiolytic products were identified: cortisone, cortisone acetate, prednisone, prednisolone and methylprednisone acetate. All the identified radiolytic products were formed as a result of oxidation of the substituent at C{sub 11}, and in some cases the oxidation was accompanied by cleavage of the ester bond. The content of impurities before irradiation did not exceed 0.8%, while after the irradiation the content of the products of radiolysis depended on the kind of the derivative and the dose, and varied from 0.6% for a dose of 25 kGy to 4.03% for a dose of 200 kGy. For some derivatives, a linear relationship was found between the loss of a given steroid content and the dose. The studied steroid derivatives are characterised by high radiochemical stability and their sterilisation by irradiation does not lead to loss of the active substance below 97%, i.e. the lower limit admissible by the pharmacopoeias.

  9. Lack of relationship between 11 beta-hydroxysteroid dehydrogenase setpoint and insulin sensitivity in the basal state and after 24h of insulin infusion in healthy subjects and type 2 diabetic patients

    NARCIS (Netherlands)

    Kerstens, MN; Riemens, SC; Sluiter, WJ; Pratt, JJ; Wolthers, BG; Dullaart, RPF

    OBJECTIVES To test whether insulin resistance in type 2 diabetes mellitus is associated with an altered overall setpoint of the 11 beta-hydroxysteroid dehydrogenase (11 beta HSD) mediated cortisol to cortisone interconversion towards cortisol, and to evaluate whether changes in insulin sensitivity

  10. 11 beta-hydroxysteroid dehydrogenase activity in proteinuric patients and the effect of angiotensin-II receptor blockade

    NARCIS (Netherlands)

    Kerstens, MN; Buter, H; Navis, GJ; Dullaart, RPF

    Background It has been suggested that an altered setpoint of the 11betaHSD-mediated cortisol to cortisone interconversion towards cortisol contributes to sodium retention in nephrotic syndrome patients. We studied the parameters of 11betaHSD activity in proteinuric patients, in particular its

  11. Lectin-like receptor for alpha 1-acid glycoprotein in the epithelium of the rat prostate gland and seminal vesicles

    DEFF Research Database (Denmark)

    Andersen, U O; Bøg-Hansen, T C; Kirkeby, S

    1996-01-01

    by mannose and N-Acetyl-D-glucosamine. RESULTS: In vitro the receptor was also inhibited by the steroid hormones cortisone, aldosterone, progesterone, and estradiol, but not by testosterone. A significant regional variation in the expression of AGP-lectin receptor and in the localization of AGP was seen...

  12. Drug: D04806 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D04806 Mixture, Drug Hydrocortisone acetate - diphenhydramine hydrochloride - fradi...omycin sulfate mixt; Strong restamin cortisone (TN) Hydrocortisone acetate [DR:D00165], Diphenhydramine hydr... Analgesics, anti-itchings, astringents, anti-inflammatory agents 2649 Others D04806 Hydrocortisone acetate

  13. Two lectin-like receptors for alpha 1-acid glycoprotein in mouse testis

    DEFF Research Database (Denmark)

    Andersen, U O; Kirkeby, S; Bøg-Hansen, T C

    1997-01-01

    . AGP-A was inhibited by testosterone, oestradiol and progesterone, while AGP-B and AGP-C were inhibited by mannose, GlcNAc, cortisone, aldosterone, oestradiol and progesterone. The receptors and the corresponding AGP glycoforms may be adhesion molecules between Sertoli cells and the spermatogenic cells...

  14. Experimental studies on radioprotection of the bladder wall by means of medicaments (experiments on 17 female domestic cats)

    Energy Technology Data Exchange (ETDEWEB)

    Pust, R.; Weidner, W.; Rothauge, C.F.; Ernst, H.

    1982-11-01

    The radioprotective effect of Cortisone, Bepanthen and Actihaemyl during a telecobalt irradiation of the bladder with a focal dose of 60 Gy was investigated in 17 female domestic cats. Different clinical and radiological and especially focally shaped modifications were caused by the administration of these medicaments. The modifications are discussed in detail.

  15. Zonal variation in the distribution of an alpha 1-acid glycoprotein glycoform receptor in human adrenal cortex

    DEFF Research Database (Denmark)

    Andersen, U O; Bøg-Hansen, T C; Kirkeby, S

    1999-01-01

    specific receptor. The binding of alpha 1-acid glycoprotein glycoform B and alpha 1-acid glycoprotein glycoform C to the glycoform specific receptor is inhibited by the steroid hormones cortisone, aldosterone, estradiol and progesterone but not by testosterone. The pronounced changes in the distribution...

  16. Proceedings of the Meeting of Australian Research Workers on Malaria (1st) Held at Ingleburn, 22-24 February 1980

    Science.gov (United States)

    1980-01-01

    A.N.U. Zymosan sensitised, LPS challenged mice show suppression of gluconeogenesis caused by the failure of PEPCK induction by cortisone . This is...Unicam SP8-100 UV /VIS Scanning accessories: a. Rate rack system b. Densitometer c. Autocel] d. Liquid Chromatography kit. - - )1AJ-T 42 -- MAJ Tony

  17. Operation of the PAVE PAWS Radar System at Beale Air Force Base, California. Part 2. Public Comment & AF Response.

    Science.gov (United States)

    1980-07-01

    study reviewed (Krupp, 1977) the immunological effect that was found could be elicited by injection of cortisone instead of exposure to RFR. This...ll6dBm or approx- imately 0.35 uV signals would be a worst case prediction. Our spectrum analyzer limited measurements to -95d4m. Effective 800 MHz

  18. [Simultaneous determination of glucocorticoids in bovine plasma by high-pressure liquid chromatography].

    Science.gov (United States)

    Sasaki, Y; Tsuiki, M; Higashimaki, T

    1982-09-20

    A method is described for the simultaneous determination of major glucocorticoids in bovine plasma, that is, Cortisol, Corticosterone and Cortisone, which includes separation by high-pressure liquid chromatography and measurement using a UV detector (254 nm). Chromatography on the Zorbax CN column is carried out with the eluent system, that is, n-hexane/ethanol (=87/13 v/v). First, Dexamethasone was selected as the best internal standard under the previously mentioned conditions. The calibration curves for the glucocorticoids were all clearly linear. The recoveries for each 5 ng of added Cortisol, Corticosterone and Cortisone were 96.7 +/- 3.2%, 100.4 +/- 2.3% and 96.1 +/- 2.2%, respectively. The reproducibility of Cortisol was good and its coefficient of variation of intraassay was small (2.7%), whereas such coefficient was not so in Corticosterone (7.7%) and Cortisone (7.3%). This appears to be due to low concentrations of Corticosterone and Cortisone in the plasma. Specificity of this method to each glucocorticoid was ascertained using plasma from adrenalectomized wethers. In addition, the correlation coefficient between measurements of Cortisol by radioimmunoassay and those by this method was 0.978. In conclusion, the method described in this paper appears to be satisfactory for the simultaneous quantification of plasma glucocorticoids.

  19. Investigation of Possible Antivitamin B-6 Properties in Irradiation Sterilized Chicken.

    Science.gov (United States)

    1981-06-01

    recommended by the SSCP (14) as described in Sigma Tech. Bul- letin No. 57- UV (7-79) (15) for the analysis of serum. Reagent rela- tionships were modified...vitamin 11-6 and 4- pyridoxic acid. J Nutr 89:19-23, 1966 20. BRIN, M. and R.W. MCKEE. Effects of x-irradiation, nitrogen mustard, fasting, cortisone , and

  20. Strategic Resources and National Security: An Initial Assessment

    Science.gov (United States)

    1975-04-01

    Antimony oxides, sulfides, in metalware, ceramic enamels, special glass, pigments, infrared reflecting camouflage paints, vulcanizing agent, UV absorber...instrument lenses, mirrors, plate glass. Glass decolorizer, colorizer UV absorber in welder’s gog- gles, special sunglasses, optical filters, food...cylinders. Orange- red pigments for plastics, paints, enamels, inks, and rubber. Stainless steel additive. Pharmaceuticals such as niacin, cortisone

  1. From etiology and pathogenesis to therapy of multiple sclerosis.

    Science.gov (United States)

    Cazzullo, C L

    1978-01-31

    The Author describes the histopathologic picture of the Multiple Sclerosis and Experimental Allergic Encephalitis and discusses some etiopathogenetic hypotheses elaborating on the immunogenetic and immunopathological aspects. The therapeutical problem is analyzed in all its various facets: cortisone derivatives, immunosuppressive products and reabilitation therapy aiming simultaneously at motion reeducation and at individual and group psycotherapy.

  2. 11Beta-HSD type 1 expression in human adipose tissue: impact of gender, obesity, and fat localization

    DEFF Research Database (Denmark)

    Paulsen, Søren Kildeberg; Pedersen, Steen Bønløkke; Fisker, Sanne

    2007-01-01

    OBJECTIVE: Pre-receptor amplification of glucocorticoids is, in part, determined by the isoenzymes 11beta-hydroxysteroid dehydrogenase (11beta-HSD) type 1 and type 2, interconverting inert cortisone and active cortisol. Increased tissue activity of cortisol may play a part in features of the meta...... relative risk of cardiovascular disease in women suffering from the metabolic syndrome. Udgivelsesdato: 2007-Aug...

  3. Antistress, Adoptogenic Activity of Sida cordifolia Roots in Mice.

    Science.gov (United States)

    Sumanth, Meera; Mustafa, S S

    2009-05-01

    Ethanol extract of roots of Sida cordifolia was evaluated for antistress, adaptogenic activity using cold restraint stress and swim endurance in mice. Mice pretreated with extract of Sida cordifolia showed significant improvement in the swim duration and reduced the elevated WBC, blood glucose and plasma cortisone.

  4. Effects of grapefruit juice on cortisol metabolism in healthy male Chinese subjects.

    Science.gov (United States)

    Xiao, Ya-Jie; Hu, Miao; Tomlinson, Brian

    2014-12-01

    Grapefruit juice (GFJ) inhibits intestinal CYP3A4 activity and it has been suggested that GFJ may also inhibit renal 11β-hydroxysteroid dehydrogenase 2 (11β-HSD2), which converts cortisol to cortisone. This study examined the effect of GFJ on the urinary excretion of cortisol, cortisone and 6β-hydroxycortisol (6β-OHC) and their ratios to asses these effects. Healthy male Chinese subjects took single doses of GFJ (200, 400, and 600 mL, respectively) at weekly intervals. Urine was collected over 24 h the day before and following GFJ intake. Subsequently, volunteers drank 400 mL GFJ for 7 days and urine was collected from 0 to 4 h daily. GFJ had dose-dependent effects on increasing cortisol excretion (P cortisol to cortisone (P cortisol (P cortisol. It increased the ratio of cortisol to cortisone and this appeared largely due to increased cortisol excretion related to impaired CYP3A4-mediated cortisol metabolism although a true inhibitory effect on 11β-HSD2 in the kidney cannot be excluded.

  5. Synthesizing a Life: An Interview with Carl Djerassi

    Science.gov (United States)

    Cardellini, Liberato

    2011-01-01

    In this interview, Carl Djerassi recalls his first years, from his pleasant childhood, to how he escaped the Nazi persecutions, to his college education in America. He remembers how with his research group he won the race for synthesis of cortisone, and how they then synthesized norethindrone, the active ingredient in oral contraceptives. Djerassi…

  6. Progressive Perforation of the Nasal Septum Due to Leishmania major: A Case of Mucosal Leishmaniasis in a Traveler.

    Science.gov (United States)

    Harrison, Nicole; Walochnik, Julia; Ramsebner, Reinhard; Veletzky, Luzia; Lagler, Heimo; Ramharter, Michael

    2017-03-01

    AbstractThis report describes a case of mucosal leishmaniasis caused by Leishmania major with destructive perforation of the nasal septum illustrating the diagnostic challenges of a rare clinical presentation of L. major infection in a traveler. The atypical presentation may have been associated with the use of cortisone as a potential trigger for the progressive destruction of the nasal septum.

  7. Corticosteroids in plasma and saliva: the influence of oral contraceptive use and pregnancy.

    NARCIS (Netherlands)

    Meulenberg, E.P.M.M.

    1995-01-01

    Cortisol in saliva is considered to be derived from the free, unbound fraction in plasma by simple diffusion through the salivary gland. Despite considerable conversion into cortisone in the salivary gland by the enzyme 11β-hydroxysteroid dehydrogenase, levels of cortisol in saliva form a good refle

  8. Targeted Gene Therapy for Breast Cancer

    Science.gov (United States)

    2005-06-01

    vein endothelial cells (HUVEC) cortisone , human FGF-fl, VEGF, ascorbic acid, heparin, were obtained from Dr Francoise Booyse (The University human EGF...cell mice resulted in a decrease in proliferative and metastatic lung cancer. Cancer Res. 2002;62:7124-7129. indices, further suggesting the feasibility

  9. [Roentgenographic pattern of interstitial pneumonia and allergic alveolitis (author's transl)].

    Science.gov (United States)

    Stender, H S

    1977-01-01

    Roentgenographic examination of the lungs permits diagnosis of inflammatory and allergic pulmonary disease with predominantly interstitial and less alveolar involvement in which pulmonary fibrosis may develop. Reaction of the sensitised lung to allergic exposure causes typical roentgenological patterns. Development of pulmonary fibrosis in interstitial lung disease can be prevented be early cortison therapy.

  10. Effect of surfactant replacement on Pneumocystis carinii pneumonia in rats

    NARCIS (Netherlands)

    E.P. Eijking (Eric); G.J. van Daal; R. Tenbrinck (Robert); A. Luijendijk (Ad); J.F. Sluiters (Hans); E. Hannappel (E.); B.F. Lachmann (Burkhard)

    1991-01-01

    textabstractThe effect of intratracheal surfactant instillation on pulmonary function in rats with Pneumocystis carinii pneumonia (PCP) was investigated. In those animals which developed PCP with severe respiratory failure after administration of cortisone acetate s. c. over 8-12 weeks, pulmonary fu

  11. Role of calcitriol and cortisol on human adipocyte proliferation and oxidative and inflammatory stress: a microarray study.

    Science.gov (United States)

    Sun, Xiaocun; Morris, Kristin L; Zemel, Michael B

    2008-01-01

    Dietary calcium inhibits adiposity, and a key underlying mechanism is suppression of calcitriol, which modulates Ca(2+) signaling and mitochondrial uncoupling in adipocytes. We demonstrated that calcitriol directly regulates adipocyte 11beta-HSD-1 expression and cortisol production in human adipocytes in vitro and dietary calcium inhibits visceral adipose tissue 11beta-HSD-1 expression in mice, indicating an interaction of calcitriol and cortisol in obesity. Consequently, we have evaluated the gene expression profile of human subcutaneous adipocytes treated with calcitriol and/or cortisone. Data analysis demonstrated significant calcitriol modulation of gene expression toward inhibition of the adipocyte apoptosis (e.g., VEGF and STC-2) and promotion of adipocyte proliferation (e.g., IGF-1 and IGF-1R). Calcitriol also up-regulated oxidative stress and inflammatory genes such as NOX-4 and TLR-3. The calcitriol/cortisone combination resulted in significant additional up-regulation of 11beta-HSD-1 and down-regulation of adiponectin expression, while cortisone exerted little independent effect in the absence of calcitriol. Overall, calcitriol stimulated a pattern of adipocyte gene expression which favored adipocyte proliferation, oxidative and inflammatory stress and visceral adiposity, and these effects were amplified in the presence of cortisone; however, this conclusion must be tempered by the adipocyte source (subcutaneous) and requires confirmation in visceral adipocytes. Copyright 2007 S. Karger AG, Basel.

  12. Glucocorticoid receptor and treatment of psychotic major depression%糖皮质激素受体与重型精神病性抑郁症的治疗

    Institute of Scientific and Technical Information of China (English)

    惠昕; 周彩红; 王明伟

    2005-01-01

    @@ 1 Introduction Psychotic major depression (PMD),which responds poorly to tricyclic anti-depressants, is a distinct syndrome of depression. hy percortisolemia (cortisone hypersecretion), a biological abnormality existing in many patients with PMD, has led to various theoretical and empirical rationales for the potential therapeutic use of anti-glucocorticoid agents in the treatment of depression.

  13. Human kidney 11 beta-hydroxysteroid dehydrogenase: regulation by adrenocorticotropin?

    Science.gov (United States)

    Diederich, S; Quinkler, M; Miller, K; Heilmann, P; Schoneshofer, M; Oelkers, W

    1996-03-01

    In ectopic adrenocorticotropin (ACTH) syndrome (EAS) with higher ACTH levels than in pituitary Cushing's syndrome and during ACTH infusion, the ratio of cortisol to cortisone in plasma and urine is increased, suggesting inhibition of renal 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) by ACTH or by ACTH-dependent steroids. Measuring the conversion of cortisol to cortisone by human kidney slices under different conditions, we tested the possibility of 11 beta-HSD regulation by ACTH and corticosteroids. Slices prepared from unaffected parts of kidneys removed because of renal cell carcinoma were incubated with unlabeled or labeled cortisol, and cortisol and cortisone were quantitated after HPLC separation by UV or radioactive detection. The 11 beta HSD activity was not influenced by incubation with increasing concentrations (10(-12)-10(-9) mol/l) of ACTH (1-24 or 1-39) for 1 h. Among 12 ACTH-dependent steroids tested (10(-9)-10(-6) mol/l), only corticosterone (IC50 = 2 x 10(-7) mol/l), 18-OH-corticosterone and 11 beta-OH-androstenedione showed a significant dose-dependent inhibition of 11 beta-HSD activity. The percentage conversion rate of cortisol to cortisone was concentration dependent over the whole range of cortisol concentrations tested (10(-8) - 10(-5) mol/l. A direct inhibitory effect of ACTH on 11 beta-HSD is, therefore, unlikely. The only steroids inhibiting the conversion of cortisol to cortisone are natural substrates for 11 beta-HSD. Kinetic studies show a saturation of the enzyme at high cortisol concentrations. Thus, the reduced percentage renal cortisol inactivation in EAS seems to be due mainly to overload of the enzyme with endogenous substrates (cortisol, corticosterone and others) rather than to direct inhibition of 11 beta-HSD by ACTH or ACTH-dependent steroids, not being substrates of 11 beta-HSD.

  14. Lack of regulation of 11beta-hydroxysteroid dehydrogenase type 1 during short-term manipulation of GH in patients with hypopituitarism.

    Science.gov (United States)

    Sigurjonsdottir, Helga A; Andrew, Ruth; Stimson, Roland H; Johannsson, Gudmundur; Walker, Brian R

    2009-09-01

    Evidence from long-term clinical studies measuring urinary steroid ratios, and from in vitro studies, suggests that GH administered for longer than 2 months down-regulates 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), thereby reducing cortisol regeneration in liver and adipose tissue. We aimed to measure acute effects of GH on 11beta-HSD1 in liver and adipose tissue in vivo, including using a stable isotope tracer. Observational studies of GH withdrawal and reintroduction in patients with hypopituitarism. Twelve men with benign pituitary disease causing GH and ACTH deficiency on stable replacement therapy for >6 months were studied after GH withdrawal for 3 weeks, and after either placebo or GH injections were reintroduced for another 3 weeks. We measured cortisol kinetics during 9,11,12,12-(2)H(4)-cortisol (d4-cortisol) infusion, urinary cortisol/cortisone metabolite ratios, liver 11beta-HSD1 by appearance of plasma cortisol after oral cortisone, and 11beta-HSD1 mRNA levels in subcutaneous adipose biopsies. GH withdrawal and reintroduction had no effect on 9,12,12-[(2)H](3)-cortisol (d3-cortisol) appearance, urinary cortisol/cortisone metabolite ratios, initial appearance of cortisol after oral cortisone, or adipose 11beta-HSD1 mRNA. GH withdrawal increased plasma cortisol 30-180 min after oral cortisone, increased d4-cortisol clearance, and decreased relative excretion of 5alpha-reduced cortisol metabolites. In this setting, GH did not regulate 11beta-HSD1 rapidly in vivo in humans. Altered cortisol metabolism with longer term changes in GH may reflect indirect effects on 11beta-HSD1. These data do not suggest that glucocorticoid replacement doses need to be increased immediately after introducing GH therapy to compensate for reduced 11beta-HSD1 activity, although dose adjustment may be required in the longer term.

  15. Profil Kadar Kortisol dan Seng pada Kambing Peranakan Etawah Saat Melahirkan yang Diberi Tambahan Seng dalam Pakannya

    Directory of Open Access Journals (Sweden)

    Sus Derthi Widhyari

    2012-11-01

    Full Text Available The objective at this experiment was to study the role of zinc supplementation (Zn in minimizingstress at parturition. Thirty etawah cross breed age 3-6 years with average body weight 30-50 kg were usedin this study and divided into three groups ; i animal were given grass + feed concentrate + ZnSO4 40 mg/kg dry matter ( control group ; (ii grass + feed concentrate + ZnSO4 60 mg/kg dry matter (treatment 1, and(iii grass + feed concentrate + ZnSO4 80 mg/kg dry matter (treatment 2, respectively drinking water weregiven ad libitum. To monitor zinc and cortisone level, blood samples were withdrawn from each animalevery two weeks starting at age of pregnancy 3 months up to two months post parturition, in addition, tomonitor the cortisone level blood samples were also collected at 1,2,3 and 7 days post parturition. The Znand cortisone serum were analyzed using atomic absorbent spectro photometric (AAS andradioimmunoassay (RIA, respectively the result showed that generally pregnancy at the beginning andget serum level at cortisone was relatively similar between the three animal groups and there was atendency to increase and reached peak at parts then gradually decrease until the and of the observation. Atparturition the lowest serum level at cortisone (19.00±18.72 mg/ml was observed in animals receiving the60/ dry matter zinc supplement compared to animal receiving 80 mg/ dry matter zinc ( 52.65 ± 30.83 mg/ml and control animal ( 75.92 ± 42.88 mg/ml. in addition serum level at Zn was significantly higher inanimal receiving 60 mg and 80 mg Zn in their diets compared to control animals. The best profiles wereseen in animal given 60 mg/kg dry matter Zn supplement. In conclusion, the addition of Zn in the diets hadsignificant effect in minimizing stress as pictured by the low serum level at cortisone at parturition.

  16. Serum levels of eleven steroid hormones following motion sickness.

    Science.gov (United States)

    Stalla, G K; Doerr, H G; Bidlingmaier, F; Sippel, W G; von Restorff, W

    1985-10-01

    In order to grade motion sickness objectively, the following 11 adrenal hormones were investigated in subjects with different motion sickness susceptibility: Aldosterone, corticosterone, 11-deoxycorticosterone, progesterone, 17-OH-progesterone, 11-deoxycortisol, cortisol, cortisone, testosterone, androstendione, dehydroepiandrosterone sulfate. Motion sickness was induced by the coriolis effect on a rotary chair. Both severe kinetosis after short rotation time and mild motion sickness after 30 min of rotation occurred together with small hormonal changes. Androstendione and 11-deoxycortisol appear to be sensitive indicators of motion sickness if the rotation time is taken into consideration. A significant increase of all hormones except progesterone, cortisone, testosterone, and dehydroepiandrosterone sulfate was observed when pronounced malaise had come after a long rotation stress (24.6 min). The changes in plasma aldosterone concentration appeared to correlate with time only. The present study demonstrates that hormonal analysis can be helpful in estimating the degree of motion sickness.

  17. Radiolytic degradation scheme for 60Co-irradiated corticosteroids

    Energy Technology Data Exchange (ETDEWEB)

    Kane, M.P.; Tsuji, K.

    1983-01-01

    The cobalt 60 radiolytic degradation products have been identified in the following corticosteroids: cortisone, cortisone acetate, hydrocortisone, hydrocortisone acetate, hydrocortisone sodium succinate, isoflupredone acetate, methylprednisolone, methylprednisolone acetate, prednisolone, prednisolone acetate, and prednisone. Two major types of degradation processes have been identified: loss of the corticoid side chain on the D-ring to produce the C-17 ketone and conversion of the C-11 alcohol, if present, to the C-11 ketone. Minor degradation products derived from other changes affecting the side chain are also identified in several corticosteroids. These compounds are frequently associated in corticosteroids as process impurities or degradation compounds. No new radiolytic compounds unique to 60Co-irradiation have been found. The majority of corticosteroids have been shown to be stable to 60Co-irradiation. The rates of radiolytic degradation ranged from 0.2 to 1.4%/Mrad.

  18. CT analyses of cerebral tumors under steroid therapy

    Energy Technology Data Exchange (ETDEWEB)

    Mueller, W.; Kretzschmar, K.; Schicketanz, K.H.

    1984-07-01

    In order to determine, by CT density and volume measurements, the influence of steroid therapy on cerebral tumors, on their perifocal edema and on the uninvolved cerebral tissue, CT follow-up studies of 37 patients were analysed. In general a decrease of tumor density is to be seen within the first 10 days of therapy. Under continuous steroid application absorption coefficients then increase again, so that no cortisone effect on the tumor remains. The tumor size does not alter: in particular at no time is growth retardation detectable under cortisone therapy. Intensity and extension of the perifocal edema decrease in two stages. From this delayed course we conclude the cytotoxic component of the tumor edema to be more extensive than supposed. Deviations appear dependent on tumor histology, which sould lead to individualied steroid application.

  19. Application of the autoblood treated by preliminary extracorporeal X-ray irradiation in the therapy of bronchial asthma patients

    Energy Technology Data Exchange (ETDEWEB)

    Goguev, N.T.

    1985-02-01

    A therapeutic method including extracorporeal x-ray irradiation of the autoblood of patients with bronchial asthma complicated by cortisone dependence and polyvalent drug intolerance, has been elaborated and clinically tested. The use of this method brings about good short-term results in 90% of cases and good long-term results in 40% of cases (14-38 months). It provides an opportunity to give up corticosteroids in more than 60% of patients and to decrease the hormone dose in the rest of cortisone-dependent patients with bronchial asthma. The above therapeutic method can be used as an independent type of treatment, especially in the presence of polyvalent drug allergy and as an element of multiple modality therapy of bronchial asthma patients. The method was used under in-patient conditions only. No side effects were marked in the course of the clinical trial. To carry out this type of therapy, patients should be thoroughly screened.

  20. Oral heparin results in the appearance of heparin fragments in the plasma of rats

    Energy Technology Data Exchange (ETDEWEB)

    Larsen, A.K.; Lund, D.P.; Langer, R.; Folkman, J.

    1986-05-01

    We have previously shown that angiogenesis inhibition and tumor regression can be accomplished by combinations of heparin or heparin fragments with cortisone. Oral heparin was also effective in combination with cortisone. We now show that a single oral dose of (/sup 35/S)heparin or (/sup 3/H)heparin (15,000 units/kg) results in continuous release of radioactive material into the bloodstream for at least 12 hr. This is associated with the presence of anti-factor Xa activity at a level of approximately equal to 0.1 unit/ml. The radioactive material is identified as oligo-, di-, and monosaccharides by its behavior in chromatographic systems, its possession of anti-factor Xa activity, and the effect of treatment with bacterial heparinase. The heparin fragments are extensively metabolized to fragments without anti-factor Xa activity that are readily subject to urinary excretion.

  1. Low-stress and high-stress singing have contrasting effects on glucocorticoid response

    Directory of Open Access Journals (Sweden)

    Daisy eFancourt

    2015-09-01

    Full Text Available Performing music in public is widely recognised as a potentially stress-inducing activity. However, despite the interest in music performance as an acute psychosocial stressor, there has been relatively little research on the effects of public performance on the endocrine system. This study examined the impact of singing in a low-stress performance situation and a high-stress live concert on levels of glucocorticoids (cortisol and cortisone in 15 professional singers. The results showed a significant decrease in both cortisol and cortisone across the low-stress condition, suggesting that singing in itself is a stress-reducing (and possibly health-promoting activity, but significant increases across the high-stress condition. This is the first study to demonstrate that singing affects glucocorticoid responses and that these responses are modulated by the conditions of performance.

  2. Faigue Avoidance Scheduling Tool (FAST) Phase II SBIR Final Report, Part 1

    Science.gov (United States)

    2006-05-01

    linearized with the proper regression coefficients it is seen that there are no systematic deviations that would obfuscate or distort the linear relationship...palate malformation, and missing digits. Primate studies have shown an association with spontaneous abortion (SAB), stillbirth, decreased weight gain and...Aleve)? Yes /No "* Ketoprofen (Orudis KT)? Yes /No "• Cortisone or other steroid medication? Yes /No "* Erythromycin? Yes / No "* Nifedipine? Yes

  3. East Europe Report, Science and Technology.

    Science.gov (United States)

    1985-01-02

    mitted, depending on the selected type of procedure. Its receiving part performs series-parallel conversion of data, decodes control symbols FLAG, ABORT ... cortisone , prostaglandins, alphaphaetoprotein, gastrin and so on. In addition, methods with radioactive tracers are used to determine blood vol- ume and...is used to make thermistors with a positive temperature coefficient . For many years, the pro- duction of them by the IFTM has covered the needs of

  4. Chemotherapy of Rodent Malaria. Part 1.

    Science.gov (United States)

    1986-09-01

    nave bene’o rried out and talc screeningisr- -x , -doj to all of te s rainz of rodent malaria held in our A : ,-W ",2h5ni q uV wn i .’n re. .,cenLI y...hepitocytes. After two hours incubation, 1 ml of MEM with ’C, anti biotics and cortisone is added to each of the ,t re . r,,,-,I r o t o i *!.,1r- S 1- a :I

  5. [The light sensitivity of corticosteroids in crystalline form. Photochemical studies. 59. (1)].

    Science.gov (United States)

    Takács, M; Ekiz-Gücer, N; Reisch, J; Gergely-Zobin, A

    1991-01-01

    The light sensitivity of corticosteroids in the solid state have been investigated and the photodecomposition rates of the compounds have been estimated by HPLC. After 48 h UV-irradiation desoxycortone acetate, hydrocortisone, hydrocortisone acetate, prednisolone, methylprednisolone, dexamethasone, betamethasone and triamcinolone acetonide decompose between 20 and 50%. Cortisone acetate, prednisone and fluocinolone acetonide show photostability in contrast to requirements of the Pharmacopeia for light protections.

  6. Role of Endotoxin in the Pathogenesis of Louse-borne Relapsing Fever and in the Mechanism of the Jarisch-Herxheimer Reaction Following Treatment of Louse-borne Relapsing Fever

    Science.gov (United States)

    1977-12-01

    J U -~ 0a 03 0 (a OC> > M C) M C) 4-CM 4-) (D0 (U Er C) 4--) r.u’) 03.i S3 - .,- cm)X 0- S- 1C) 0) 4-) C 4-JC) E) 2 uv 0 C.C 4 c.’- 3-. ejC 3--- JCC...fifteen patients were randomly treated with acetaminophen 1.3 g orally, 1hdro- cortisone 1 g intravenously, or nothing in combination with erythromycint

  7. Isotope-dilution TurboFlow-LC-MS/MS method for simultaneous quantification of ten steroid metabolites in serum

    DEFF Research Database (Denmark)

    Søeborg, Tue; Frederiksen, Hanne; Johannsen, Trine Holm

    2017-01-01

    An isotope-dilution TurboFlow-LC-MS/MS method for simultaneous quantification of the ten steroid metabolites dehydroepiandrosterone sulfate (DHEAS), progesterone, 17α-hydroxyprogesterone (17-OHP), Δ4-androstenedione (Adione), corticosterone, 11-deoxycortisol, cortisol, cortisone, testosterone (T)...... possible only to include some of these analytes for specific diagnostic purposes which make the new method an extremely useful tool in the clinical laboratory....

  8. Water-filtered infrared-A (wIRA) can act as a penetration enhancer for topically applied substances

    OpenAIRE

    Sterry, Wolfram; Ackermann, Hanns; Hoffmann, Gerd; Schanzer, Sabine; Meyer, Lars; Grone, Diego; Otberg, Nina; Lademann, Jürgen

    2008-01-01

    Background: Water-filtered infrared-A (wIRA) irradiation has been shown to enhance penetration of clinically used topically applied substances in humans through investigation of functional effects of penetrated substances like vasoconstriction by cortisone. Aim of the study: Investigation of the influence of wIRA irradiation on the dermatopharmacokinetics of topically applied substances by use of optical methods, especially to localize penetrating substances, in a prospective randomised contr...

  9. Personality and Coping Strategies During Submarine Missions

    OpenAIRE

    Sandal, Gro M.; Endresen, Inger M.; Vaernes, Ragnar; Ursin, Holger

    2003-01-01

    Relations between personality profiles, measured by the Personality Characteristics Inventory (PCI), and habitual coping strategies, measured by the Utrecht Coping List (UCL), were investigated in a sample of submarine personnel and office employees. The predictive validity of these instruments were examined for reported stress, health complaings, and salivary cortisone measures during 3 submarine missions. PCI and UCL were completed before the missions, and questionnaires and saliva were col...

  10. Wassergefiltertes Infrarot A (wIRA) kann als Penetrationsverstärker für topisch aufgetragene Substanzen wirken

    OpenAIRE

    Otberg, N; Grone, D; Meyer, L.; Schanzer, S; Hoffmann, G.; Ackermann, H; Sterry, W.; Lademann, J.

    2008-01-01

    Background: Water-filtered infrared-A (wIRA) irradiation has been shown to enhance penetration of clinically used topically applied substances in humans through investigation of functional effects of penetrated substances like vasoconstriction by cortisone. Aim of the study: Investigation of the influence of wIRA irradiation on the dermatopharmacokinetics of topically applied substances by use of optical methods, especially to localize penetrating substances, in a prospective randomised c...

  11. A Non-Dimensional Analysis of Cardiovascular Response to Cold Stress. Part I. Identification of the Physical Parameters that Govern the Thermoregulatory Function of the Cardiovascular System.

    Science.gov (United States)

    1983-09-01

    13. Cortisone (from Adrenal), 14. Hydrocortisone, or Cortisol (from Adrenal), 15. Corticosterones "A", "B", or "S" (from Adrenal), 16. Epinephrine...widened arterio-venous-oxygen-difference. Moreover, blood coming back to the lungs with less oxygen, by the same mechanism, is able to extract more oxygen...or exist in duplicate (e.g., kidneys, liver, lungs ), or can still function under anaerobic or ischemic conditions (e.g., muscle), or are larger than

  12. Influence of Steroids on Oxidant Generation in Activated Human Granulocytes and Mononuclear Leukocytes

    Science.gov (United States)

    2003-07-01

    and hemorrhage- induced lung injury (31), and lung injury induced by hind limb ischemia (11). Administering scavengers of reactive oxygen species or...be altering protein synthesis. For PMNs, E2 or P4 had no effect on oxidants, whereas all hydro- cortisone concentrations showed a modest trend for...activated and non-activated MNCs (35). Similarly, activated macrophages derived from lungs or a macrophage cell line (J774) treated with pharmacological

  13. Trichothecenes Mycotoxin Studies

    Science.gov (United States)

    1986-02-01

    003 0.020 + .006 "(C) 0.008 + .003 0.010 ; .004 cecum 0.008 + .004 0.014 + .005 large intestine 0.009 ; .003 0.009 7 .003 lungs 0.008 + .002 0.014...the stress of treatment, as suggested by Sato et al (1978), because cortisone causes lymphopenia within 4 hours. The observed lymphocytosis may have

  14. Uncommon appearance of radiation-induced pneumonitis during radiotherapy of patients with small-cell bronchiogenic carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Karstens, J.H.; Ammon, J.; Frik, W.

    1982-10-15

    Four cases of distinctive radiation-induced pneumonitis with severe clinical symptoms were observed during combined therapy of 52 patients with small-cell bronchial carcinoma. Withdrawal of corticosteroids was identified as the most probable cause, due to the fact that a time correlation between cortison withdrawal and the onset of clinical symptoms was found in all four patients. Possible consequences for future therapy measures are pointed out.

  15. Dehydrogenase and Oxoreductase Activities of Porcine Placental 11Beta-Hydroxysteroid Dehydrogenase

    Science.gov (United States)

    2016-06-07

    Subsequently, samples were thawed and extracted with ethyl acetate to obtain tritiated steroids. These extracts were sub- jected to thin layer chromatography...containing .02 M EDTA (PBS) to remove most radio- activity. Tissue fragments were then homogenized in PBS and aliquots removed for DNA analysis (32). In...either 3H-cortisol or 3H-cortisone were used as substrate. Incubations were conducted as above-noted and DNA measures conducted. Statistical

  16. Corticosteroid treatment increases parasite numbers in murine giardiasis.

    OpenAIRE

    Nair, K V; Gillon, J.; Ferguson, A

    1981-01-01

    Corticosteroid therapy is known to be hazardous in patients with occult infection but the mechanism by which the host parasite relationship is altered by steroids is not known.We have used an intestinal protozoal parasite, Giardia muris, to examine the effects of corticosteroids on the number of parasites in the intestine in the course of a primary infection. A single injection of cortisone acetate, subcutaneously, one day before oral inoculation of CBA mice with 1000 cysts of Giardia muris, ...

  17. Simultaneous assay of cortisol and dexamethasone improved diagnostic accuracy of the dexamethasone suppression test.

    Science.gov (United States)

    Ueland, Grethe Å; Methlie, Paal; Kellmann, Ralf; Bjørgaas, Marit; Åsvold, Bjørn O; Thorstensen, Ketil; Kelp, Oskar; Thordarson, Hrafnkell B; Mellgren, Gunnar; Løvås, Kristian; Husebye, Eystein S

    2017-06-01

    The overnight dexamethasone (DXM) suppression test (DST) has high sensitivity, but moderate specificity, for diagnosing hypercortisolism. We have evaluated if simultaneous measurement of S-DXM may correct for variable DXM bioavailability and increase the diagnostic performance of DST, and if saliva (sa) is a feasible adjunct or alternative to serum. Prospective study of DST was carried out in patients with suspected Cushing's syndrome (CS) (n = 49), incidentaloma (n = 152) and healthy controls (n = 101). Cortisol, cortisone and DXM were assayed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Three hundred and two subjects underwent DST; S-cortisol was ≥50 nmol/L in 83 patients, of whom 11 had CS and 27 had autonomous cortisol secretion. The lower 2.5 percentile of S-DXM in subjects with negative DST (n = 208) was 3.3 nmol/L, which was selected as the DXM cut-off level. Nine patients had the combination of low S-DXM and positive DST. Of these, three had been misdiagnosed as having autonomous cortisol secretion. DST results were highly reproducible and confirmed in a replication cohort (n = 58). Patients with overt CS had significantly elevated post-DST sa-cortisol and sa-cortisone levels compared with controls; 23 of 25 with autonomous cortisol secretion had elevated sa-cortisone and 14 had elevated sa-cortisol. Simultaneous measurement of serum DXM and cortisol reduced false-positive DSTs by 20% and improved the specificity. S-DXM >3.3 nmol/L is sufficient for the suppression of cortisol <50 nmol/L. Measurement of glucocorticoids in saliva is a non-invasive and easy procedure and post-DST sa-cortisone was found particularly useful in the diagnosis of CS. © 2017 European Society of Endocrinology.

  18. Tissue-specific increases in 11beta-hydroxysteroid dehydrogenase type 1 in normal weight postmenopausal women.

    Directory of Open Access Journals (Sweden)

    Therése Andersson

    Full Text Available With age and menopause there is a shift in adipose distribution from gluteo-femoral to abdominal depots in women. Associated with this redistribution of fat are increased risks of type 2 diabetes and cardiovascular disease. Glucocorticoids influence body composition, and 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1 which converts inert cortisone to active cortisol is a putative key mediator of metabolic complications in obesity. Increased 11betaHSD1 in adipose tissue may contribute to postmenopausal central obesity. We hypothesized that tissue-specific 11betaHSD1 gene expression and activity are up-regulated in the older, postmenopausal women compared to young, premenopausal women. Twenty-three pre- and 23 postmenopausal, healthy, normal weight women were recruited. The participants underwent a urine collection, a subcutaneous adipose tissue biopsy and the hepatic 11betaHSD1 activity was estimated by the serum cortisol response after an oral dose of cortisone. Urinary (5alpha-tetrahydrocortisol+5beta-tetrahydrocortisol/tetrahydrocortisone ratios were higher in postmenopausal women versus premenopausal women in luteal phase (P<0.05, indicating an increased whole-body 11betaHSD1 activity. Postmenopausal women had higher 11betaHSD1 gene expression in subcutaneous fat (P<0.05. Hepatic first pass conversion of oral cortisone to cortisol was also increased in postmenopausal women versus premenopausal women in follicular phase of the menstrual cycle (P<0.01, at 30 min post cortisone ingestion, suggesting higher hepatic 11betaHSD1 activity. In conclusion, our results indicate that postmenopausal normal weight women have increased 11betaHSD1 activity in adipose tissue and liver. This may contribute to metabolic dysfunctions with menopause and ageing in women.

  19. Drug: D00165 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available tisone D00165 Hydrocortisone acetate (JP16/USP) D DERMATOLOGICALS D07 CORTICOSTEROIDS, DERMATOLOGICAL PREPARATIONS D07A CORTICOST...cortisone acetate (JP16/USP) D07X CORTICOSTEROIDS, OTHER COMBINATIONS D07XA Corti...MIC HORMONAL PREPARATIONS, EXCL. SEX HORMONES AND INSULINS H02 CORTICOSTEROIDS FOR SYSTEMIC USE H02A CORTICOST... S01CB03 Hydrocortisone D00165 Hydrocortisone acetate (JP16/USP) S02 OTOLOGICALS S02B CORTICOST

  20. In vivo activity of 11beta-hydroxysteroid dehydrogenase type 1 and free fatty acid-induced insulin resistance.

    Science.gov (United States)

    Mai, K; Kullmann, V; Bobbert, T; Maser-Gluth, C; Möhlig, M; Bähr, V; Pfeiffer, A F H; Spranger, J; Diederich, S

    2005-10-01

    Free fatty acids (FFAs) induce hepatic insulin resistance and enhance hepatic gluconeogenesis. Glucocorticoids (GCs) also stimulate hepatic gluconeogenesis. The aim of this study was to investigate whether the FFA-induced hepatic insulin resistance is mediated by increased activity of hepatic 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), accompanied by elevated hepatic cortisol levels. Following a 10-h overnight fast, six healthy male volunteers were investigated. A euglycaemic hyperinsulinaemic clamp was performed during lipid or saline infusion. To assess hepatic 11beta-HSD1 activity, plasma cortisol levels were measured after oral administration of cortisone acetate during lipid or saline infusion. In addition, 11beta-HSD activities were determined in vivo by calculating the urinary ratios of GC metabolites. Lipid infusion increased FFAs (5.41 +/- 1.00 vs. 0.48 +/- 0.20 mmol/l; P < 0.005) and significantly increased insulin resistance [glucose infusion rate (GIR) 6.02 +/- 2.60 vs. 4.08 +/- 2.15 mg/kg/min; P < 0.005]. After lipid and saline infusions no changes in 11beta-HSD1 activity were found, neither by changes in cortisone acetate to cortisol conversion nor by differences in urinary free cortisol (UFF) or cortisone (UFE), 5beta-tetrahydrocortisol (THF), 5alpha-THF, cortisone (THE), UFF/UFE and (5alpha-THF + THF)/THE ratios. We found no change in hepatic and whole-body 11beta-HSD1 activity during acute FFA-induced insulin resistance. Further studies are necessary to clarify whether 11beta-HSD1 in muscle and adipose tissue is influenced by FFAs and whether 11beta-HSD1 is involved in other conditions of insulin resistance.

  1. Diagnostic value of concentration profiles of glucocorticosteroids and endocannabinoids in hair.

    Science.gov (United States)

    Krumbholz, Aniko; Anielski, Patricia; Reisch, Nicole; Schelling, Gustav; Thieme, Detlef

    2013-10-01

    Endogenous corticosteroids and endocannabinoids are both known to be involved in stress adaption and anti-inflammatory and immuneregulatory effects. The application of hair as retrospective specimen for long-term recording of corticosteroids and its association with stress-induced biochemical alterations was intensively examined. To evaluate the stability and correlation of various parameters of the endocannabinoid and corticosteroid systems, a prospective study was carried out. Hair samples were collected monthly over a pregnancy cycle (sixth week of pregnancy to 9 weeks postpartum). By comparison of hair concentrations in particular segments (ie, grown in the same time span but collected at different times), an examination of analyte stability in hair was achieved. Additionally, the comparison of proximal segments provided on biochemical information that is independent of alteration due to physical instability. The detection limits of a validated procedure using solid-phase extraction cleanup and liquid chromatography-mass spectrometry proved to be suitable to identify the endogenous levels of cortisol (limits of detection = 1.6 pg/mg), cortisone (2.1 pg/mg), anandamide (AEA, 0.3 pg/mg), and 2-arachidonoylglycerol (15 pg/mg). Corticosteroid concentrations in corresponding hair segments were found to be reduced with increasing hair age; an average decline of cortisol and cortisone by 50% in 4 months was estimated. Independently, an increase of cortisol and cortisone in proximal segments collected during pregnancy was confirmed, which is assumed to be stress related. Endocannabinoids proved to be by far more stable, as demonstrated by subsequent monthly collection of corresponding segments and there was hardly any washout of AEA detectable. Elevated hair concentrations of AEA and 2-arachidonoylglycerol were detected in the first-second trimester of pregnancy, which corresponds to negative correlations between AEA, cortisol, and cortisone.

  2. 11beta-hydroxysteroid dehydrogenase type 1 regulates glucocorticoid-induced insulin resistance in skeletal muscle.

    LENUS (Irish Health Repository)

    Morgan, Stuart A

    2009-11-01

    Glucocorticoid excess is characterized by increased adiposity, skeletal myopathy, and insulin resistance, but the precise molecular mechanisms are unknown. Within skeletal muscle, 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) converts cortisone (11-dehydrocorticosterone in rodents) to active cortisol (corticosterone in rodents). We aimed to determine the mechanisms underpinning glucocorticoid-induced insulin resistance in skeletal muscle and indentify how 11beta-HSD1 inhibitors improve insulin sensitivity.

  3. Defects in the HSD11 gene encoding 11[beta]-hydroxysteriod dehydrogenase are not found in patients with apparent mineralocorticoid excess or 11-oxoreductase deficiency

    Energy Technology Data Exchange (ETDEWEB)

    Nikkila, H.; White, P.C. (Cornell Univ. Medical College, New York, NY (United States)); Tannin, G.M. (Rainbow Babies and Children' s Hospital, Cleveland, OH (United States)); New, M.I.; Taylor, N.F. (King' s College School of Medicine and Dentistry, London (United Kingdom)); Kalaitzoglou, G.; Monder, C. (Population Council, New York, NY (United States))

    1993-09-01

    The syndrome of apparent mineralocorticoid excess (AME) is a form of low renin hypertension that is thought to be caused by congenital deficiency of 11[beta]-hydroxysteroid dehydrogenase (11HSD) activity. This enzyme converts cortisol to cortisone and apparently prevents cortisol from acting as a ligand for the mineralocorticoid (type I) receptor. It also catalyzes the reverse oxoreductase (cortisone to cortisol) reaction. Four patients with AME and the parents of the first patient described (now deceased) were analyzed for mutations in the cloned HSD11 gene encoding an 11HSD enzyme. A patient with suspected cortisone reductase deficiency was also studied. No gross deletions or rearrangements in the HSD11 gene were apparent on hybridizations of blot of genomic DNA. Direct sequencing of polymerase chain reaction-amplified fragments corresponding to the coding sequences, intronexon junctions, and proximal untranslated regions of this gene revealed no mutations. AME may involve mutations in a gene for another enzyme with 11HSD activity or perhaps another cortisol metabolizing enzyme. 48 refs., 2 figs., 2 tabs.

  4. Necrotizing enterocolitis, pathogenesis and the protector effect of prenatal corticosteroids Enterocolite necrosante: resposta imflamatória x corticoterapia pré-natal

    Directory of Open Access Journals (Sweden)

    Alexander Roberto Precioso

    2002-09-01

    Full Text Available Necrotizing enterocolitis is the most frequently occurring gastrointestinal disorder in premature neonates. Animal models of necrotizing enterocolitis and prenatal administration of cortisone have demonstrated that cortisone may accelerate maturation of the mucosal barrier, therefore reducing the incidence of this gastrointestinal disorder. The authors present a review of the literature of the most important risk factors associated with necrotizing enterocolitis, such as inflammatory gastrointestinal mediators, enteral feeding and bacterial colonization, and immaturity of the gastrointestinal barrier, and we emphasize the necessity for additional studies to explore the prenatal administration of cortisone as a preventive strategy for necrotizing enterocolitis.A enterocolite necrosante é a mais freqüente patologia gastrointestinal adquirida no período neonatal, acometendo preferencialmente o recém-nascido prematuro. Estudos experimentais sugerem que a corticoterapia pré-natal acelera a maturação da mucosa gastrintestinal, levando a diminuição da incidência desta doença. Os autores apresentam uma revisão da literatura em relação aos principais fatores fisiopatológicos associados a enterocolite necrosante, tais como mediadores inflamatórios gastrintestinais, nutrição enteral e colonização bacteriana e imaturidade gastrintestinal e enfatizam a necessidade de mais estudos que avaliem a influencia da corticoterapia pré-natal com fator de prevenção da enterocolite necrosante.

  5. Substrate binding process and mechanistic functioning of type 1 11β-hydroxysteroid dehydrogenase from enhanced sampling methods.

    Directory of Open Access Journals (Sweden)

    Angelo D Favia

    Full Text Available In humans, type 1 11β-hydroxysteroid dehydrogenase (11β-HSD-1 plays a key role in the regulation of the glucocorticoids balance by converting the inactive hormone cortisone into cortisol. Numerous functional aspects of 11β-HSD-1 have been understood thanks to the availability at the Worldwide Protein Data Bank of a number of X-ray structures of the enzyme either alone or in complex with inhibitors, and to several experimental data. However at present, a complete description of the dynamic behaviour of 11β-HSD-1 upon substrate binding is missing. To this aim we firstly docked cortisone into the catalytic site of 11β-HSD-1 (both wild type and Y177A mutant, and then we used steered molecular dynamics and metadynamics to simulate its undocking. This methodology helped shedding light at molecular level on the complex relationship between the enzyme and its natural substrate. In particular, the work highlights a the reason behind the functional dimerisation of 11β-HSD-1, b the key role of Y177 in the cortisone binding event, c the fine tuning of the active site degree of solvation, and d the role of the S228-P237 loop in ligand recognition.

  6. Progesterone - new therapy in mild carpal tunnel syndrome? Study design of a randomized clinical trial for local therapy

    Directory of Open Access Journals (Sweden)

    Ginanneschi Federica

    2010-04-01

    Full Text Available Abstract Background Local corticosteroid injection for carpal tunnel syndrome (CTS provides greater clinical improvement in symptoms one month after injection compared to placebo but significant symptom relief beyond one month has not been demonstrated and the relapse of symptoms is possible. Neuroprotection and myelin repair actions of the progesterone was demonstrated in vivo and in vitro study. We report the design of a randomized controlled trial for the local injection of cortisone versus progesterone in "mild" idiopathic CTS. Methods Sixty women with age between 18 and 60 years affected by "mild" idiopathic CTS, diagnosed on the basis of clinical and electrodiagnostic tests, will be enrolled in one centre. The clinical, electrophysiological and ultasonographic findings of the patients will be evaluate at baseline, 1, 6 and 12 months after injection. The major outcome of this study is to determine whether locally-injected progesterone may be more beneficial than cortisone in CTS at clinical levels, tested with symptoms severity self-administered Boston Questionnaire and with visual analogue pain scale. Secondary outcome measures are: duration of experimental therapy; improvement of electrodiagnostic and ultrasonographic anomalies at various follow-up; comparison of the beneficial and harmful effects of the cortisone versus progesterone. Conclusion We have designed a randomized controlled study to show the clinical effectiveness of local progesterone in the most frequent human focal peripheral mononeuropathy and to demonstrate the neuroprotective effects of the progesterone at the level of the peripheral nervous system in humans.

  7. Skin cancer development in mice exposed chronically to immunosuppressive agents.

    Science.gov (United States)

    Daynes, R A; Harris, C C; Connor, R J; Eichwald, E J

    1979-04-01

    Inbred female C3Hf/HeN, murine mammary tumor virus-negative mice exposed to either UV light or benzo[a]pyrene (BP), were subjected to four different chronic immunosuppressive regimens to determine their effect on skin cancer development. The immunosuppressive agents were cyclophosphamide, methotrexate, cortisone, and heterologous antilymphocyte globulin. Because of an unexpectedly high morbidity and mortality of mice exposed to chronic immunosuppressive measures, the dosages were kept at a level that permitted them to survive but did not prolong allogeneic skin graft survival and lower antibody titers, nor did this level diminish proliferative responses of lymphocytes to mitogens or allogeneic lymphocytes. Nevertheless, the latency periods (time interval between beginning of medication and appearance of skin tumors) of tumors in mice exposed to immunosuppressant measures were significantly shortened in several groups of mice exposed to UV and subjected to cyclophosphamide, cortisone, or antilymphocyte globulin and mice exposed to BP and subjected to cortisone acetate. In 3 groups, spindle cell tumors (fibrosarcomas) shifted to squamous cell carcinomas. A suppressed immune function would not be regarded as the mechanism for the observed responses because immunosuppression was not detected in the experimental mice.

  8. Hormone induced changes in lactase glycosylation in developing rat intestine.

    Science.gov (United States)

    Chaudhry, Kamaljit Kaur; Mahmood, Safrun; Mahmood, Akhtar

    2008-11-01

    Lactase exists in both soluble and membrane-bound forms in suckling rat intestine. The distribution of lactase and its glycosylated isoforms in response to thyroxine or cortisone administration has been studied in suckling rats. 75% of lactase activity was detected, associated with brush borders, compared to 24% in the soluble fraction of 8-day-old rats. Thyroxine treatment enhanced soluble lactase activity to 34%, whereas particulate fraction was reduced to 67% compared to controls. Cortisone administration reduced soluble lactase activity from 24% in controls to 12% with a concomitant increase in membrane-bound activity to 89%. Western blot analysis revealed lactase signal, corresponding to 220 kDa in both the soluble and membrane fractions, which corroborated the enzyme activity data. The elution pattern of papain solubilized lactase from agarose-Wheat Germ agglutinin, or Concanavalin A or Jacalin agglutinin columns was different in the suckling and adult rat intestines. Also the elution profile of lactase activity from agarose-lectin columns was modulated in cortisone, thyroxine, and insulin injected pups, which suggests differences in glycosylated isoforms of lactase under these conditions. These findings suggest the role of these hormones in inducing changes in lactase glycosylation during postnatal development of intestine, which may contribute to adult-type hypolactasia in rats.

  9. [Temporomandibular joint arthropathy in situ steroid injection].

    Science.gov (United States)

    Gagé, J; Gallucci, A; Arnaud, M; Chossegros, C; Foletti, J M

    2016-09-01

    Temporomandibular disorders (TMDs) affect the masticatory muscles and the temporomandibular joints (TMJs). TMDs most often result from occlusal and/or muscular disorders and are then called primary or idiopathic TMDs. Less frequently, TMDs are related to local (trauma, infection) or general (rheumatoid arthritis) causes and are then called secondary TMDs. A little known iatrogenic cause of secondary TDM is the osteoarthritis that may be induced by intra-articular cortisone injections. We report one case of condylar lysis that occurred after one single intra-articular cortisone injection. A 62-years-old woman consulted for a long-lasting TMD on the left side manifesting itself through pain and noise. She benefited one year before from an intra-articular injection of cortisone by her rheumatologist for repeated closed lock of her left TMJ. Physical examination showed limited mouth opening with deviation on the left side. Lateral movements on the right side were impossible. The panoramic X-ray showed a condylar lysis on the left side that was on the CT scan. MRI additionally showed an anteriorly displaced and severely reshaped disc and an articular inflammation without intra-articular effusion. TMJ osteoarthritis secondary to unique or repeated intra-articular steroid injections are little-known. They are clinically expressed as typical TMDs and characterized on X-rays by condylar lysis and inflammation. Intra-articular injections of steroids are not totally harmless and other treatments must be preferred. Copyright © 2016. Published by Elsevier Masson SAS.

  10. Apparent mineralocorticoid excess syndrome: report of one family with three affected children.

    Science.gov (United States)

    Al-Harbi, Taiba; Al-Shaikh, Adnan

    2012-01-01

    The syndrome of apparent mineralocorticoid excess (AME) is an autosomal recessive disorder characterized by hypertension, hypokalemia, low renin, and hypoaldosteronism. It is caused by deficiency of 11β-hydroxysteroid dehydrogenase, which results in a defect of the peripheral metabolism of cortisol to cortisone. As a consequence, the serum cortisol half-life (T½) is prolonged, ACTH is suppressed, and serum cortisol concentration is normal. The hormonal diagnosis of the disorder is made by the increased ratio of urine-free cortisol to cortisone. In patients with AME, this ratio is 5-18, while in normal individuals it is causing the syndrome of AME. We report three siblings - two female and one male - with the syndrome of apparent mineralocorticoid excess who presented with hypertension, hypokalemia, low renin, and low aldosterone levels. The finding of abnormally high ratios of 24-h urine-free cortisol to cortisone in our three patients (case 1, 8.4; case 2, 25; and case 3, 7.5) confirmed the diagnosis of apparent mineralocorticoid excess syndrome in these children. They were treated with oral potassium supplements. The addition of spironolactone resulted in a decrease in blood pressure, rise in serum potassium and a gradual increase in plasma renin activity in all three. In this study, the genetic testing of those three siblings with the typical clinical features of AME has detected missense mutation c.662C>T (p.Arg208Cys) in exon 3 of the HSD11B2 gene in the homozygous state.

  11. Skeletal muscle 11beta-HSD1 controls glucocorticoid-induced proteolysis and expression of E3 ubiquitin ligases atrogin-1 and MuRF-1.

    Directory of Open Access Journals (Sweden)

    Katrin Biedasek

    Full Text Available Recent studies demonstrated expression and activity of the intracellular cortisone-cortisol shuttle 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1 in skeletal muscle and inhibition of 11beta-HSD1 in muscle cells improved insulin sensitivity. Glucocorticoids induce muscle atrophy via increased expression of the E3 ubiquitin ligases Atrogin-1 (Muscle Atrophy F-box (MAFbx and MuRF-1 (Muscle RING-Finger-1. We hypothesized that 11beta-HSD1 controls glucocorticoid-induced expression of atrophy E3 ubiquitin ligases in skeletal muscle. Primary human myoblasts were generated from healthy volunteers. 11beta-HSD1-dependent protein degradation was analyzed by [(3H]-tyrosine release assay. RT-PCR was used to determine mRNA expression of E3 ubiquitin ligases and 11beta-HSD1 activity was measured by conversion of radioactively labeled [(3H]-cortisone to [(3H]-cortisol separated by thin-layer chromatography. We here demonstrate that 11beta-HSD1 is expressed and biologically active in interconverting cortisone to active cortisol in murine skeletal muscle cells (C2C12 as well as in primary human myotubes. 11Beta-HSD1 expression increased during differentiation from myoblasts to mature myotubes (p < 0.01, suggesting a role of 11beta-HSD1 in skeletal muscle growth and differentiation. Treatment with cortisone increased protein degradation by about 20% (p < 0.001, which was paralleled by an elevation of Atrogin-1 and MuRF-1 mRNA expression (p < 0.01, respectively. Notably, pre-treatment with the 11beta-HSD1 inhibitor carbenoxolone (Cbx completely abolished the effect of cortisone on protein degradation as well as on Atrogin-1 and MuRF-1 expression. In summary, our data suggest that 11beta-HSD1 controls glucocorticoid-induced protein degradation in human and murine skeletal muscle via regulation of the E3 ubiquitin ligases Atrogin-1 and MuRF-1.

  12. Syntheses of stable isotope-labeled 6 beta-hydroxycortisol, 6 beta-hydroxycortisone, and 6 beta-hydroxytestosterone.

    Science.gov (United States)

    Furuta, Takashi; Suzuki, Atsushi; Matsuzawa, Mitsuhiro; Shibasaki, Hiromi; Kasuya, Yasuji

    2003-09-01

    A method is described for the preparation of two types of multi-labeled 6 beta-hydroxycortisol containing either five deuterium atoms at C-19 methyl and C-1 methylene or four 13C atoms at C-1, C-2, C-4, and C-19 in addition to the five deuterium atoms for use as analytical internal standards for gas chromatography-mass spectrometry (GC-MS). BMD derivatives of [1,1,19,19,19-2H(5)]cortisone and [1,2,4,19-13C(4),1,1,19,19,19-2H(5)]cortisone (cortisone-2H(5)-BMD and cortisone-13C(4),2H(5)-BMD) were first synthesized via indan synthon method starting from optical active 11-oxoindanylpropionic acid and labeled isopropenyl anion ([1,1,3,3,3-2H(5)]- or [1,3-13C(2),1,1,3,3,3-2H(5)]isopropenyl anion). The labeled isopropenyl anion was prepared from commercially available [1,1,1,3,3,3-2H(6)]- or [1,3-13C(2),1,1,1,3,3,3-2H(6)]acetone. Ultraviolet (UV) irradiated autoxidation at C-6 position of 3-ethyl-3,5-dienol ether derivatives of the labeled cortisone-BMDs gave 6 beta-hydroxy-[1,1,19,19,19-2H(5)]cortisone-BMD and 6 beta-hydroxy-[1,2,4,19-13C(4),1,1,19,19,19-2H(5)]cortisone-BMD, respectively, as a mixture of 6 beta- and 6 alpha-epimers in a ratio of 4:1. Separation of 6 beta- and 6 alpha-epimers by thin-layer chromatography (TLC) and subsequent hydrolysis of the BMD group at C-17 gave pure labeled 6 beta-hydroxycortisone. After protecting the keto group at C-3 of the labeled 6 beta-hydroxycortisone-BMD as semicarbazone, reduction of 11-keto group with NaBH(4) and subsequent removal of the C-3 and C-17 protecting groups gave 6beta-hydroxy-[1,1,19,19,19-2H(5)]cortisol (6 beta-hydroxycortisol-2H(5)) and 6 beta-hydroxy-[1,2,4,19-13C(4),1,1,19,19,19-2H(5)]cortisol (6 beta-hydroxycortisol-13C(4),2H(5)), respectively, as a mixture of 6 beta- and 6 alpha-epimers (6 beta:6 alpha=4.4:1). The isotopic compositions of 6 beta-hydroxycortisol-2H(5) and 6 beta-hydroxycortisol-13C(4),2H(5) were 90.9 and 92.1 at.%, respectively. Furthermore, 6 beta-hydroxy-[1 alpha,16,16,17 alpha-2H(4

  13. Glucocorticoids and 11β-HSD1 are major regulators of intramyocellular protein metabolism

    Science.gov (United States)

    Hassan-Smith, Zaki K; Doig, Craig L; Sherlock, Mark; Stewart, Paul M; Lavery, Gareth G

    2016-01-01

    The adverse metabolic effects of prescribed and endogenous glucocorticoid excess, ‘Cushing’s syndrome’, create a significant health burden. While skeletal muscle atrophy and resultant myopathy is a clinical feature, the molecular mechanisms underpinning these changes are not fully defined. We have characterized the impact of glucocorticoids upon key metabolic pathways and processes regulating muscle size and mass including: protein synthesis, protein degradation, and myoblast proliferation in both murine C2C12 and human primary myotube cultures. Furthermore, we have investigated the role of pre-receptor modulation of glucocorticoid availability by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in these processes. Corticosterone (CORT) decreased myotube area, decreased protein synthesis, and increased protein degradation in murine myotubes. This was supported by decreased mRNA expression of insulin-like growth factor (IGF1), decreased activating phosphorylation of mammalian target of rapamycin (mTOR), decreased phosphorylation of 4E binding protein 1 (4E-BP1), and increased mRNA expression of key atrophy markers including: atrogin-1, forkhead box O3a (FOXO3a), myostatin (MSTN), and muscle-ring finger protein-1 (MuRF1). These findings were endorsed in human primary myotubes, where cortisol also decreased protein synthesis and increased protein degradation. The effects of 11-dehydrocorticosterone (11DHC) (in murine myotubes) and cortisone (in human myotubes) on protein metabolism were indistinguishable from that of CORT/cortisol treatments. Selective 11β-HSD1 inhibition blocked the decrease in protein synthesis, increase in protein degradation, and reduction in myotube area induced by 11DHC/cortisone. Furthermore, CORT/cortisol, but not 11DHC/cortisone, decreased murine and human myoblast proliferative capacity. Glucocorticoids are potent regulators of skeletal muscle protein homeostasis and myoblast proliferation. Our data underscores the potential use

  14. Consumption of Green Coffee Reduces Blood Pressure and Body Composition by Influencing 11β-HSD1 Enzyme Activity in Healthy Individuals: A Pilot Crossover Study Using Green and Black Coffee

    Directory of Open Access Journals (Sweden)

    R. Revuelta-Iniesta

    2014-01-01

    Full Text Available Dietary polyphenols may have a protective role against the development of CVD. Thus, we aimed to investigate the effects of green coffee (GC, rich in chlorogenic acid, and black coffee (BC on cardiovascular markers. A randomised pilot crossover study was performed on healthy subjects who consumed both coffees for 2 weeks. We measured anthropometry, blood pressure, and arterial elasticity after each intervention and collected urine samples to monitor antioxidant capacity. Free cortisol and cortisone levels were obtained from urine and analysed by specific ELISA methods. Systolic blood pressure (P=0.018 and arterial elasticity (P=0.001 were significantly reduced after GC. BMI (P=0.04 for BC; P=0.01 for GC and abdominal fat (P=0.01 for BC; P=0.009 for GC were also significantly reduced with no changes in energy intake. Urinary free cortisol was significantly reduced from 125.6±85.9 nmol/day to 76.0±54.9 nmol/day following GC and increased to 132.1±89.1 nmol/day after BC. Urinary free cortisone increased by 18% following BC and 9% following GC (nonsignificant. Cortisol/cortisone ratio (indicating 11β-HSD1 activity was reduced after GC (from 3.5±1.9 to 1.7±1.04, P=0.002. This suggests that GC can play a role in reducing cardiovascular risk factors. Further research including hypertensive and overweight individuals will now be justified to clarify whether GC could have a therapeutic role in CVD.

  15. Effects of Carbenoxolone on the Canine Pituitary-Adrenal Axis.

    Directory of Open Access Journals (Sweden)

    Takahiro Teshima

    Full Text Available Cushing's disease caused by pituitary corticotroph adenoma is a common endocrine disease in dogs. A characteristic biochemical feature of corticotroph adenomas is their relative resistance to suppressive negative feedback by glucocorticoids. The abnormal expression of 11beta-hydroxysteroid dehydrogenase (11HSD, which is a cortisol metabolic enzyme, is found in human and murine corticotroph adenomas. Our recent studies demonstrated that canine corticotroph adenomas also have abnormal expression of 11HSD. 11HSD has two isoforms in dogs, 11HSD type1 (HSD11B1, which converts cortisone into active cortisol, and 11HSD type2 (HSD11B2, which converts cortisol into inactive cortisone. It has been suggested that glucocorticoid resistance in corticotroph tumors is related to the overexpression of HSD11B2. Therefore it was our aim to investigate the effects of carbenoxolone (CBX, an 11HSD inhibitor, on the healthy dog's pituitary-adrenal axis. Dogs were administered 50 mg/kg of CBX twice each day for 15 days. During CBX administration, no adverse effects were observed in any dogs. The plasma adrenocorticotropic hormone (ACTH, and serum cortisol and cortisone concentrations were significantly lower at day 7 and 15 following corticotropin releasing hormone stimulation. After completion of CBX administration, the HSD11B1 mRNA expression was higher, and HSD11B2 mRNA expression was significantly lower in the pituitaries. Moreover, proopiomelanocortin mRNA expression was lower, and the ratio of ACTH-positive cells in the anterior pituitary was also significantly lower after CBX treatment. In adrenal glands treated with CBX, HSD11B1 and HSD11B2 mRNA expression were both lower compared to normal canine adrenal glands. The results of this study suggested that CBX inhibits ACTH secretion from pituitary due to altered 11HSD expressions, and is potentially useful for the treatment of canine Cushing's disease.

  16. Inhibition of microsomal cortisol production by (-)-epigallocatechin-3-gallate through a redox shift in the endoplasmic reticulum--a potential new target for treating obesity-related diseases.

    Science.gov (United States)

    Szelényi, Péter; Révész, Katalin; Konta, Laura; Tüttõ, Anna; Mandl, József; Kereszturi, Éva; Csala, Miklós

    2013-01-01

    Conversion of cortisone to cortisol by 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) in the endoplasmic reticulum (ER) of the target cells is a major determinant of glucocorticoid action, and plays an important role in the development of obesity-related diseases. Inhibition of 11βHSD1 activity is, therefore, considered as a promising novel strategy for the treatment of metabolic syndrome and diabetes. Tea flavanols and their major representative, epigallocatechin gallate are known as antiobesity and antidiabetic agents. Their impacts on blood glucose level, hepatic glucose production, and insulin responsiveness resemble those observed on inhibition or depletion of 11βHSD1. We aimed to study the effect of epigallocatechin gallate on 11βHSD1 activity in ER-derived rat liver microsomes by measuring cortisone and cortisol with HPLC. Cortisol production was efficiently suppressed in a concentration dependent manner in intact microsomal vesicles. However, this effect was abolished by membrane permeabilization; and the three proteins involved in the overall process (11βHSD1, hexose 6-phosphate dehydrogenase, and glucose 6-phosphate transporter) were not or only mildly affected. Further investigation revealed the oxidation of luminal NADPH to NADP⁺, which attenuates cortisone reduction and favors cortisol oxidation in this compartment. Such a redox shift in the ER lumen might contribute to the beneficial health effects of tea flavanols and should be regarded as a promising strategy for the development of novel selective 11βHSD1 inhibitors to treat obesity-related diseases.

  17. Studies of Relationships among Bile Flow, Liver Plasma Membrane NaK-ATPase, and Membrane Microviscosity in the Rat

    Science.gov (United States)

    Keeffe, Emmet B.; Scharschmidt, Bruce F.; Blankenship, Nancy M.; Ockner, Robert K.

    1979-01-01

    Liver plasma membrane (LPM) NaK-ATPase activity, LPM fluidity, and bile acid-independent flow (BAIF) were studied in rats pretreated with one of five experimental agents. Compared with controls, BAIF was increased 24.6% by thyroid hormone and 34.4% by phenobarbital, decreased by ethinyl estradiol, but unchanged by propylene glycol and cortisone acetate. Parallel to the observed changes in BAIF, NaK-ATPase activity also was increased by thyroid hormone (40.8%) and decreased by ethinyl estradiol (26.2%). In contrast, NaK-ATPase activity failed to increase after phenobarbital but did increase 36% after propylene glycol and 34.8% after cortisone acetate. Thus BAIF and NaK-ATPase activity did not always change in parallel. The NaK-ATPase Km for ATP was not affected by any of these agents. LPM fluidity, measured by fluorescence polarization using the probe 1,6-diphenyl-1,3,5-hexatriene, was found to be increased by propylene glycol, thyroid hormone, and cortisone acetate, decreased by ethinyl estradiol, and unaffected by phenobarbital. Thus in these cases, induced changes in LPM fluidity paralleled those in NaK-ATPase activity. In no case did Mg-ATPase or 5′-nucleotidase activities change in the same direction as NaK-ATPase, and the activity of neither of these enzymes correlated with LPM fluidity, thus indicating the selective nature of the changes in LPM enzyme activity caused by the agents. These findings indicate that LPM fluidity correlates with NaK-ATPase activity and may influence the activity of this enzyme. However, the nature of the role of LPM NaK-ATPase in bile secretion is uncertain and needs further study. Images PMID:227937

  18. Urine volume dependency of specific dehydroepiandrosterone (DHEA) and cortisol metabolites in healthy children.

    Science.gov (United States)

    Shi, Lijie; Wudy, Stefan A; Maser-Gluth, Christiane; Hartmann, Michaela F; Remer, Thomas

    2011-01-01

    Urine volume should be considered as a confounder when using urinary free cortisol (UFF) and cortisone (UFE) to assess glucocorticoid (GC) status. We aimed to examine whether adrenal androgen (AA) metabolites may be also affected by urine volume in healthy children. To compare the flow dependence of GC and AA metabolites, specific GC metabolites were examined. In 24-h urine samples of 120 (60 boys) healthy children (4-10 yr), steroid profiles were determined by GC-MS analysis, UFF and UFE by radioimmunoassay. To assess daily AA and GC secretion rates, 7 quantitatively most important AA (∑C19) and GC (∑C21) metabolites were summed. Sum of DHEA and its 16α-hydroxylated metabolites were denoted as DHEA&M. Association of urine volume with AA (∑C19, DHEA&M, DHEA, 16α-hydroxy-DHEA, 3β,16α,17β-androstenetriol) and GC (∑C21, UFF, UFE, 6β-hydroxycortisol, 20α-dihydrocortisol) were examined in linear regression models. Among the examined AA metabolites, 16α-hydroxy-DHEA (β=0.56, pDHEA (β=0.43, p=0.05) showed relatively strong association with urine volume. A trend was seen for ∑C19 (β=0.23, p=0.08), but not for DHEA&M (p>0.1). Regarding GC metabolites, urine volume showed a stronger association with cortisol's direct metabolites, i.e., cortisone, 6β-hydroxycortisol and 20α-dihydrocortisol (β=0.4-0.6, pDHEA, 16α-hydroxy-DHEA, 6β-hydroxycortisol, and 20α-dihydrocortisol may also depend on urine volume. The intrarenal production of the latter three and cortisone might explain their relative strong water-flow-dependency. Total AA or GC secretion marker appears not to be relevantly confounded by urine volume. Copyright © 2010 Elsevier Inc. All rights reserved.

  19. Acute in vivo regulation of 11beta-hydroxysteroid dehydrogenase type 1 activity by insulin and intralipid infusions in humans.

    Science.gov (United States)

    Wake, Deborah J; Homer, Natalie Z M; Andrew, Ruth; Walker, Brian R

    2006-11-01

    Extraadrenal regeneration of cortisol by 11beta-hydroxysteroid dehydrogenase type 1 (11HSD1) is increased after a mixed meal. It is unknown which tissue is responsible and whether this reflects the complex transcriptional control of 11HSD1 or posttranscriptional control exerted by supply of reduced nicotinamide adenine dinucleotide phosphate from hexose-6-phosphate dehydrogenase. The objective of this study was to test whether hyperinsulinemia and/or increased serum free fatty acids increase whole-body and intraadipose 11HSD1, and whether adipose 11HSD1 switches from dehydrogenase to reductase activity. In nine healthy men, we measured whole-body cortisol regeneration (by iv infusion of 9,11,12,12-[2H]4 -cortisol) and intra-adipose interconversion of cortisol and cortisone (by sc microdialysis infusion of [3H]4 -cortisol and [3H]2 -cortisone in separate cannulae) during: 1) a hyperinsulinemic euglycemic clamp; 2) iv lipid infusion (Intralipid 20% fat emulsion); and 3) saline infusion, each for 3.5 h. Hyperinsulinemia increased rate of appearance of 9,12,12-[2H]3 -cortisol (19.3 +/- 0.8 vs. 16.7 +/- 1.1 nmol/min with saline, P adipose, the predominant reaction was reductase conversion of cortisone to cortisol (after 3.5 h of saline infusion, reaching 11.0 +/- 2.7% per hour reductase vs. 5.2 +/- 1.3 dehydrogenase, P effects on whole-body deuterated cortisol metabolism, but increased both dehydrogenase and reductase (reaching 16.7 +/- 1.8, P adipose. Hyperinsulinemia and increased free fatty acids induce acute increases in 11HSD1 activity in adipose tissue that are not attributable to a switch from dehydrogenase to reductase. Hyperinsulinemia also increases systemic cortisol regeneration. These effects may enhance intracellular cortisol concentrations after a meal.

  20. Anti-diabetic and anti-adipogenic effects of a novel selective 11β-hydroxysteroid dehydrogenase type 1 inhibitor, 2-(3-benzoyl)-4-hydroxy-1,1-dioxo-2H-1,2-benzothiazine-2-yl-1-phenylethanone (KR-66344).

    Science.gov (United States)

    Park, Ji Seon; Rhee, Sang Dal; Kang, Nam Sook; Jung, Won Hoon; Kim, Hee Youn; Kim, Jun Hyoung; Kang, Seung Kyu; Cheon, Hyae Gyeong; Ahn, Jin Hee; Kim, Ki Young

    2011-04-15

    The selective inhibitors of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) have considerable potential for treating type 2 diabetes mellitus and metabolic syndrome. In the present study, we investigated the anti-diabetic and anti-adipogenic effects of 2-(3-benzoyl)-4-hydroxy-1,1-dioxo-2H-1,2-benzothiazine-2-yl-1-phenylethanone (KR-66344), as a 11β-HSD1 inhibitor; we also investigated the underlying molecular mechanisms in the cortisone-induced 3T3-L1 adipogenesis model system and C57BL/6-Lep(ob/ob) mice. KR-66344 concentration-dependently inhibited 11β-HSD1 activity in human liver microsome, mouse C2C12 myotube and human SW982 cells. In the C57BL/6-Lep(ob/ob) mice study, the administration of KR-66344 (200mg/kg/d, orally for 5 days) improved the glucose intolerance as determined by the oral glucose tolerance test, in which the area under the curve (AUC) of the plasma glucose concentration was significantly reduced by 27% compared with the vehicle treated group. Further, KR-66344 suppressed adipocyte differentiation on cortisone-induced adipogenesis in 3T3-L1 cells is associated with the suppression of the cortisone-induced mRNA levels of FABP4, G3PD, PPARγ2 and Glut4, and 11β-HSD1 expression and activity. Our results additionally demonstrate evidence showing that KR-66344 improved glycemic control and inhibited adipogenesis via 11β-HSD1 enzyme activity. Taken together, these results may provide evidence of the therapeutic potential of KR-66344, as a 11β-HSD1 inhibitor, in obesity and type 2 diabetes patients with metabolic syndrome.

  1. Consumption of green coffee reduces blood pressure and body composition by influencing 11β-HSD1 enzyme activity in healthy individuals: a pilot crossover study using green and black coffee.

    Science.gov (United States)

    Revuelta-Iniesta, R; Al-Dujaili, E A S

    2014-01-01

    Dietary polyphenols may have a protective role against the development of CVD. Thus, we aimed to investigate the effects of green coffee (GC), rich in chlorogenic acid, and black coffee (BC) on cardiovascular markers. A randomised pilot crossover study was performed on healthy subjects who consumed both coffees for 2 weeks. We measured anthropometry, blood pressure, and arterial elasticity after each intervention and collected urine samples to monitor antioxidant capacity. Free cortisol and cortisone levels were obtained from urine and analysed by specific ELISA methods. Systolic blood pressure (P = 0.018) and arterial elasticity (P = 0.001) were significantly reduced after GC. BMI (P = 0.04 for BC; P = 0.01 for GC) and abdominal fat (P = 0.01 for BC; P = 0.009 for GC) were also significantly reduced with no changes in energy intake. Urinary free cortisol was significantly reduced from 125.6 ± 85.9 nmol/day to 76.0 ± 54.9 nmol/day following GC and increased to 132.1 ± 89.1 nmol/day after BC. Urinary free cortisone increased by 18% following BC and 9% following GC (nonsignificant). Cortisol/cortisone ratio (indicating 11β-HSD1 activity) was reduced after GC (from 3.5 ± 1.9 to 1.7 ± 1.04, P = 0.002). This suggests that GC can play a role in reducing cardiovascular risk factors. Further research including hypertensive and overweight individuals will now be justified to clarify whether GC could have a therapeutic role in CVD.

  2. The role of glucocorticoids in sodium retention in cirrhotic patients

    DEFF Research Database (Denmark)

    Hansen, Martin Højmark; Kristensen, Steffen Skott; Schaffalitzky de Muckadell, Ove B

    2012-01-01

    Abstract Objective. Cirrhotic patients have an increased ratio of urinary cortisol to cortisone metabolites, indicating decreased renal 11-β-hydroxysteroid dehydrogenase type-2 activity. This suggests that cortisol - by activation of the mineralocorticoid receptor - may contribute to the abnormal...... sodium retention evident in cirrhosis. The aim was to elucidate the role of glucocorticoids in sodium retention in decompensated cirrhotic patients. Methods. A randomized, double-blind, placebo-controlled, crossover study was performed in nine patients with alcoholic cirrhosis of the liver. A washout....... Conclusion. These results indicate that endogenous glucocorticoids contribute to the sodium retention in patients with alcoholic cirrhosis of the liver....

  3. Diagnosis and Management of Trichothecene in the Swine Model

    Science.gov (United States)

    1988-09-01

    not found in the 3 rats given saline alone. It is well known that cortisone and other glucocorticolds cause lysis of the small, non-blastogenic... abortions in swine. Can. Vet. 3. 19:71-74. Weaver, G. A., Kurtz, H. J., and Bates, F. Y. (1981) Diacetoxyscirpenol toxicity in pigs. Res. Vet. Sdi. 31:131...from 3 to I mg/kg. !9 However, because of the relatively large coefficient of variation (25 to 50%), this trend was not statistically significant. We

  4. Separations of corticosteroids using electrochemically modulated liquid chromatography: Selectivity enhancements at a porous graphitic carbon stationary phase

    Energy Technology Data Exchange (ETDEWEB)

    Ting, E.Y.; Porter, M.D. [Ames Lab., IA (United States)]|[Iowa State Univ., Ames, IA (United States)

    1997-02-15

    Electrochemically modulated liquid chromatography has been applied to the separation of a mixture of structurally similar corticosteroids (i.e., prednisone, prednisolone, cortisone, and hydrocortisone) using a porous graphitic carbon stationary phase. Changes in the voltage applied to the column markedly affected the efficiency as well as the elution order of the separation, with the mixture fully resolved at large negative values of applied potential. Mechanistic aspects in terms of the influence of changes in the applied voltage on the extent of the interactions between these analytes and the stationary phase are briefly discussed. 19 refs., 2 figs.

  5. Drug: D00986 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D00986 Drug Fludrocortisone acetate (JP16/USP); Florinef acetate (TN) C23H31FO6 422...l organs 24 Hormones 245 Adrenal hormone preparations 2452 Cortisones D00986 Fludrocortisone acetate (JP16/U...OIDS FOR SYSTEMIC USE, PLAIN H02AA Mineralocorticoids H02AA02 Fludrocortisone D00986 Fludrocortisone acetate...cement/Modifying (Adrenal) Fludrocortisone D00986 Fludrocortisone acetate (JP16/USP) Target-based classifica...eceptor [HSA:2908] [KO:K05771] Fludrocortisone [ATC:H02AA02] D00986 Fludrocortisone acetate (JP16/USP) CAS:

  6. Unusual appearance of the osteoarthropathy in connection with psoriatric erythrodermia

    Energy Technology Data Exchange (ETDEWEB)

    Heuck, F.

    1982-12-01

    Follow-up study is reported of an unusual osteoarthropathy showing considerable changes in the vertebral column and connected with a psoriatric erythrodermia. X-ray findings are growing metaplastic ossifications in the capsular ligaments, which are extremely prominent in the regions of shoulder joints and hip joints. In the vertebral column cervical and lumbal regions are especially attacked and in fibroostitis huge metaplastic ossifications of the ligaments develop, which radiologically look very similar to the picture of an ankylapoietic spondylosis. After longterm therapy with high doses of cortisone the patient developed diabetes mellitus and Cushing-syndrome. The arising complications soon caused death.

  7. Churg-Strauss syndrome presenting as polymiositis: report of a case

    Directory of Open Access Journals (Sweden)

    E. Presotto

    2011-06-01

    Full Text Available We reported the case of a male patient with Churg-Strauss syndrome (CSS heralding as symptoms typical of polymiositis. During high-dose cortisone therapy (1.5 mg/kg/day, he developed a severe multiplex mononeuritis, poorly responsive to immunoglobulins and methotrexate administration. After 6 months he developed a partial deficiency of the right sciatic popliteus and the radial nerves. Sural nerve biopsy showed a characteristic necrotizing vasculitis of the epineural vessels with granulocyte and eosinophil infiltrates. In the course of CSS, peripheral nervous system involvement is frequent and can lead to disability. For this reason, it must be promptly recognized and properly treated.

  8. Importance of radiologic early symptoms in diagnosis and therapy of necrosis of the head of the femur

    Energy Technology Data Exchange (ETDEWEB)

    Stahl, C.; Kang, C.H.; Phlvers, E.; Haasters, J.; Thuemler, P. (Essen Univ. (Gesamthochschule) (Germany, F.R.))

    1985-02-01

    Early roentgenographic signs of aseptic necrosis are changes after infarction without flattening of the femoral head or subchondral decalcification (crescent sign). 121 patients with femoral head necrosis, in 99 of idiopathic origin and in 22 after cortisone treatment, were examined. The first sign of infarction is represented by the intensification of the bright regions at the lateral and medial aspect of the femoral head with emphasis on the lateral aspect near to the femoral neck. Special radiographic changes after infarction are discussed. The diagnosis of bilateral involvement determines the prognosis of the disease and its treatment. A careful study of the anamnesis is most important for prognostic reasons.

  9. The role of the endoplasmic reticulum in the metabolism of "xenobiotica"

    OpenAIRE

    Meyer, Arne

    2013-01-01

    Short-chain dehydrogenase/reductase (SDR) enzymes play a key role in the metabolism of steroids, fatty acids, prostaglandins and xenobiotic chemicals. This thesis investigated the role of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in the metabolism of xenobiotics. It further addressed species-specific differences of the inhibition of 11β-HSD1 and some related microsomal SDRs by xenobiotics. 11β-HSD1 catalyzes the conversion of the inactive glucocorticoids cortisone and 11-dehydrocorti...

  10. Quantitative high-performance liquid chromatographic determination of delta 4-3-ketosteroids in adrenocortical extracts.

    Science.gov (United States)

    Ballerini, R; Chinol, M; Ghelardoni, M

    1980-05-30

    A high-performance liquid chromatographic method is described for the determination of seven steroids in adrenocortical extracts showing a delta 4-3-ketonic conjugated system. The seven steroids (cortisol, cortisone, 11-dehydrocorticosterone, corticosterone, 11-deoxycortisol, aldosterone and 11-deoxycorticosterone) were separated with a chloroform-methanol gradient on a 5-micron silica column and with a water-acetonitrile gradient on a 10-micron RP-8 column. Effluents were monitored by UV absorption at 242 nm. Quantitative analysis was performed by comparing peak areas, which are proportional to the amounts of the individual substances (external standard method). The method is rapid, sensitive, easy to perform and reproducible.

  11. Annual Research Progress Report Letterman Army Institute of Research

    Science.gov (United States)

    1974-06-30

    Institute of Research Department of Maxlllofaclal Sciences «ooNufc* Presidio of San Francisco, CA 94129 mUNCirU. IIIWtiTla»TO« (***•* UV " C/.J. A—*m...have been Inltltated or conducted under this work unit during the past year: STUDY MO. 19 The effect of stress and hydro- cortisone treatwent on...nutriture. A number or enzymes are known to require pyridOAal-P04 (P-PO^) as the active vitamin B6 cofactor, including the transarainase systems. The UV

  12. Iliotibial band Z-lengthening.

    Science.gov (United States)

    Richards, David P; Alan Barber, F; Troop, Randal L

    2003-03-01

    Iliotibial band friction syndrome (ITBFS) is a common overuse injury reported to afflict 1.6% to 12% of runners. It results from an inflammatory response secondary to excessive friction that occurs between the lateral femoral epicondyle and the iliotibial band. Initial treatments include rest, anti-inflammatory medication, modalities (ice or heat), stretching, physical therapy, and possibly a cortisone injection. In recalcitrant cases of ITBFS, surgery has been advocated. This report describes a surgical technique of Z-lengthening of the iliotibial band in patients presenting with lateral knee pain localized to the iliotibial band at the lateral femoral epicondyle and Gerdy's tubercle who failed all nonoperative efforts.

  13. Green tea and one of its constituents, Epigallocatechine-3-gallate, are potent inhibitors of human 11β-hydroxysteroid dehydrogenase type 1.

    Directory of Open Access Journals (Sweden)

    Jan Hintzpeter

    Full Text Available The microsomal enzyme 11β-hydroxysteroid deydrogenase type 1 (11β-HSD1 catalyzes the interconversion of glucocorticoid receptor-inert cortisone to receptor- active cortisol, thereby acting as an intracellular switch for regulating the access of glucocorticoid hormones to the glucocorticoid receptor. There is strong evidence for an important aetiological role of 11β-HSD1 in various metabolic disorders including insulin resistance, diabetes type 2, hypertension, dyslipidemia and obesity. Hence, modulation of 11β-HSD1 activity with selective inhibitors is being pursued as a new therapeutic approach for the treatment of the metabolic syndrome. Since tea has been associated with health benefits for thousands of years, we sought to elucidate the active principle in tea with regard to diabetes type 2 prevention. Several teas and tea specific polyphenolic compounds were tested for their possible inhibition of cortisone reduction with human liver microsomes and purified human 11β-HSD1. Indeed we found that tea extracts inhibited 11β-HSD1 mediated cortisone reduction, where green tea exhibited the highest inhibitory potency with an IC50 value of 3.749 mg dried tea leaves per ml. Consequently, major polyphenolic compounds from green tea, in particular catechins were tested with the same systems. (--Epigallocatechin gallate (EGCG revealed the highest inhibition of 11β-HSD1 activity (reduction: IC50 = 57.99 µM; oxidation: IC50 = 131.2 µM. Detailed kinetic studies indicate a direct competition mode of EGCG, with substrate and/or cofactor binding. Inhibition constants of EGCG on cortisone reduction were Ki = 22.68 µM for microsomes and Ki = 18.74 µM for purified 11β-HSD1. In silicio docking studies support the view that EGCG binds directly to the active site of 11β-HSD1 by forming a hydrogen bond with Lys187 of the catalytic triade. Our study is the first to provide evidence that the health benefits of green tea and its

  14. Addison's disease and pregnancy: case report.

    Science.gov (United States)

    Cosimo, Caterina; Franco, Ciro

    2009-10-01

    Addisonian crises, a rare but life-threatening event in pregnant women, may accompany stressful conditions such as labor, puerperium, infection, hyperemesis gravidarum or surgery. A 36-year-old woman, primigravida, with Addison's disease, diagnosed when she was 10 year-old and treated with cortisone and fludrocortisone. The therapy was regulated to avoid adrenal crisis during pregnancy. The woman underwent to caesarean section at 38th week and gave birth to a normal baby. The successful management of pregnant women with Addison's disease, regarding her state and that of the foetus, reassures those women that nowadays Addison's disease and pregnancy are not incompatible when proper monitoring and management is provided.

  15. Green tea and one of its constituents, Epigallocatechine-3-gallate, are potent inhibitors of human 11β-hydroxysteroid dehydrogenase type 1.

    Science.gov (United States)

    Hintzpeter, Jan; Stapelfeld, Claudia; Loerz, Christine; Martin, Hans-Joerg; Maser, Edmund

    2014-01-01

    The microsomal enzyme 11β-hydroxysteroid deydrogenase type 1 (11β-HSD1) catalyzes the interconversion of glucocorticoid receptor-inert cortisone to receptor- active cortisol, thereby acting as an intracellular switch for regulating the access of glucocorticoid hormones to the glucocorticoid receptor. There is strong evidence for an important aetiological role of 11β-HSD1 in various metabolic disorders including insulin resistance, diabetes type 2, hypertension, dyslipidemia and obesity. Hence, modulation of 11β-HSD1 activity with selective inhibitors is being pursued as a new therapeutic approach for the treatment of the metabolic syndrome. Since tea has been associated with health benefits for thousands of years, we sought to elucidate the active principle in tea with regard to diabetes type 2 prevention. Several teas and tea specific polyphenolic compounds were tested for their possible inhibition of cortisone reduction with human liver microsomes and purified human 11β-HSD1. Indeed we found that tea extracts inhibited 11β-HSD1 mediated cortisone reduction, where green tea exhibited the highest inhibitory potency with an IC50 value of 3.749 mg dried tea leaves per ml. Consequently, major polyphenolic compounds from green tea, in particular catechins were tested with the same systems. (-)-Epigallocatechin gallate (EGCG) revealed the highest inhibition of 11β-HSD1 activity (reduction: IC50 = 57.99 µM; oxidation: IC50 = 131.2 µM). Detailed kinetic studies indicate a direct competition mode of EGCG, with substrate and/or cofactor binding. Inhibition constants of EGCG on cortisone reduction were Ki = 22.68 µM for microsomes and Ki = 18.74 µM for purified 11β-HSD1. In silicio docking studies support the view that EGCG binds directly to the active site of 11β-HSD1 by forming a hydrogen bond with Lys187 of the catalytic triade. Our study is the first to provide evidence that the health benefits of green tea and its polyphenolic compounds may

  16. Clinical picture and problems of keratoplasty in Richner-Hanhart syndrome (tyrosinemia type II).

    Science.gov (United States)

    Sayar, R B; von Domarus, D; Schäfer, H J; Beckenkamp, G

    1988-01-01

    The Richner-Hanhart syndrome seen in a middle-aged woman is described. The patient had the typical clinical manifestations of tyrosinemia II with a bilateral keratopathy, palmar and plantar hyperkeratosis. The patient was subjected to a specific diet and to perforating keratoplasty. Postoperative systemic therapy with steroids had a negative influence on the clinical manifestations; dendritic lesions which developed on the corneal graft disappeared after interruption of the systemic steroid therapy. This suggests that cortisone treatment after keratoplasty should be avoided in this special metabolic disorder.

  17. Synthesis of 21-Thioureido or 21-Ureidocorticosteroids as NOS Inhibitors

    Institute of Scientific and Technical Information of China (English)

    PENG Jiu-He; HAN Chong; LI Bing-Jie; CHENG Jin-Pei

    2003-01-01

    @@ Aryl or alkyl thioureas are known as NOS inhibitors, [1~ 4] in this paper we reported the synthesis of 21-thioureido or 21-ureidocorticosteroids as potential NOS inhibitors. The title compounds were prepared from primary 21aminocorticosteroids and in vivo generated aryl isothiocynates. For comparison, 21-ureidocorticoids were synthesized in a similar way. Scheme 1 shows the preparation of 21-thioureido and 21-ureidoprednisolone. Other corticosteroids' 2 1-thioureido or ureido derivatives, such as hydrocortisone' s, methylprednisolne' s, dexamethasone' s, betamethasone' s, RS' s, cortisone' s and prednisone' s, were also prepared. Preliminary pharmacology evaluation showed that they possessed NOS inhibiting activities.

  18. [Corticosteroid hormones in the blood and adrenals of the aurochs Bison bonasus].

    Science.gov (United States)

    Belova, T A; Kuntsevich, M V

    1978-01-01

    Using thin-layer chromatography, studies have been made on corticosteroids in the aurochs Bison bonasus. Hydrocortison, corticosteron, aldosteron, 11-dehydrocorticosteron and 11-deoxycorticosteron were found in the suprarenals. Besides these hormones, the blood of the aurochs contains cortison, 17-oxy-11-deoxycorticosteron ("S" compounds) and unidentified fraction. Compounds revealed in the blood of the aurochs were also found in the bison and ox. The ratio of hydrocortison to corticosteron together with 11-dehydro- and 11-deoxycorticosteron is equal to 0.42 +/- 0.06 in the suprarenals and to 0.34 +/- 0.01 in the blood.

  19. A Case of Recurrent Acute Pancreatitis Due to Intra-Articular Corticosteroid Injection

    Directory of Open Access Journals (Sweden)

    Patompong Ungprasert

    2014-03-01

    Full Text Available Context Corticosteroid is a well-established cause of drug-induced pancreatitis. However, acute pancreatitis from intraarticularinjection of corticosteroid has never been described. Case report A 69-year-old male presented with acuteabdominal pain and was diagnosed with acute pancreatitis. The patient had one episode of acute pancreatitis two yearearlier. Both episodes occurred after intra-articular cortisone injection. Investigations for other causes of pancreatitis werenegative. Conclusion We report the first case of acute pancreatitis from intra-articular corticosteroid injection. Physiciansshould be aware of this adverse reaction of corticosteroid that can even occur with local administration.

  20. Drug: D00976 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available cortisone cypionate D DERMATOLOGICALS D07 CORTICOSTEROIDS, DERMATOLOGICAL PREPARATIONS D07A CORTICOSTEROIDS,... PLAIN D07AA Corticosteroids, weak (group I) D07AA02 Hydrocortisone D00976 Hydrocortisone cypionate D07X CORTICOST...D07XA01 Hydrocortisone D00976 Hydrocortisone cypionate H SYSTEMIC HORMONAL PREPARATIONS, EXCL. SEX HORMONES AND INSULINS H02 CORTICOS...TEROIDS FOR SYSTEMIC USE H02A CORTICOSTEROIDS FOR SYSTEMIC USE, PLAIN H02AB Glucoco...ortisone cypionate S02 OTOLOGICALS S02B CORTICOSTEROIDS S02BA Corticosteroids S02BA01 Hydrocortisone D00976

  1. Inactivation of corticosteroids in intestinal mucosa by 11 beta-hydroxysteroid: NADP oxidoreductase (EC 1. 1. 1. 146)

    Energy Technology Data Exchange (ETDEWEB)

    Burton, A.F.; Anderson, F.H.

    1983-10-01

    Activity of the enzyme 11 beta-hydroxysteroid:NADP oxidoreductase (EC 1.1.1.146) in human intestinal mucosa was determined by incubating scraped mucosa with /sup 3/H-cortisone and /sup 14/C-cortisol; these steroids were then extracted, separated chromatographically, and the radioactivity assayed to determine simultaneously both reductase and dehydrogenase activities. This was the only significant metabolic alteration which the substrate underwent. Only two cases had slight (5 and 13%) reductase activity. In 35 patients, 16 male and 19 female, including seven cases of Crohn's disease, three ulcerative colitis, five diverticulitis, two undergoing surgery for repair of injuries and 18 for carcinoma of colon or rectum, cortisol was converted to cortisone in 15 min with a wide range of values distributed uniformly up to 85% dehydrogenation, with a mean of 42%. When tissue homogenates were fortified with coenzymes, excess NADPH lowered dehydrogenase activity 81%; excess NADP increased dehydrogenase activity 2-fold in three cases. It is possible that a value is characteristic of an individual but perhaps more likely enzyme activity varies with metabolic events involving changes in the coenzyme levels in mucosa, and a random sampling might be expected to yield such a distribution of values. In any event, where activity is high most of the cortisol is inactivated within minutes. It is suggested that synthetic corticoids which escape such metabolic alteration might, except during pregnancy, prove superior in the treatment of conditions such as inflammatory bowel disease.

  2. Comparison of the transplacental pharmacokinetics of cortisol and triamcinolone acetonide in the rhesus monkey

    Energy Technology Data Exchange (ETDEWEB)

    Slikker, W. Jr.; Althaus, Z.R.; Rowland, J.M.; Hill, D.E.; Hendrickx, A.G.

    1982-11-01

    The late gestational age rhesus monkey was used to study the transplacental pharmacokinetics of radiolabeled triamcinolone acetonide (TAC) and cortisol. Tritiated-TAC and (/sup 14/C)cortisol were administered simultaneously via the maternal radial vein were administered simultaneously via the maternal radial vein and blood samples were serially drawn from catheters implanted in both the maternal femoral artery and fetal umbilical vein and artery. High-performance liquid chromatography of the processed blood samples revealed that from 93 to 100% of the /sup 3/H in the fetal circulation was parent TAC, whereas only 14 to 49% of the /sup 14/C was cortisol during the 40-min period after dose administration. Fetal tissue samples taken at 3 hr after dose administration showed that 75 to 96% of the /sup 3/H present was TAC, whereas no cortisol was observed. TAC demonstrated dose-independent kinetics. Samples collected from the umbilical vein of the in situ placenta after fetectomy revealed that cortisol was extensively converted to cortisone by the placenta, whereas TAC was refractory to placental metabolism. This placental conversion of cortisol to cortisone and the further metabolism and conjugation of cortisol by the fetoplacental unit resulted in a fetal to maternal plasma cortisol ratio of 0.2. In contrast, the lack of placental or fetoplacental metabolism of TAC resulted in a fetal to maternal plasma TAC ratio of 0.6.

  3. Improvements and limitations of the subrenal capsule assay for determining tumour sensitivity to cytostatic drugs

    Energy Technology Data Exchange (ETDEWEB)

    Edelstein, M.B.; Ruiter, D.J. (Rijksuniversiteit Leiden (Netherlands). Hospital); Smink, T. (Rijksuniversiteit Leiden (Netherlands). Hospital; Radiobiological Inst., TNO, Rijswijk (Netherlands)); Visser, W. (University Hospital, Rotterdam (Netherlands)); Puttens, L.M. van (Radiobiological Inst., TNO, Rijswijk (Netherlands))

    1984-12-01

    Cyclophosphamide (CY) prevented the host response from occurring in treated animals, and we therefore evaluated CY and other immunosuppressive forms of pretreatment in normal mice using the subrenal capsule assay initially for transplanted and later also for primary tumours. CY pretreatment, 4 or 4.5 Gy whole-body irradiation and cortisone were superior to silica in reducing host cell infiltration, and irradiation as pretreatment has become our routine technique. The addition of cortisone acetate to irradiation was of minor benefit in only 1/3 transplanted lines. When primary tumours were tested, the irradiation was only rarely able to completely prevent cellular infiltration. Only 7/11 ovarian tumours and 3/9 lung tumours were evaluable as tumour specimens (>50% tumour) in preirradiated mice. The degree of infiltration and fibrosis was similar in transplants in irradiated normal mice or in athymic nude mice, suggesting that these phenomena are largely due to properties of the tumours rather than of the host. The limitations of the technique to some cell lines and occasional primary tumours is obvious.

  4. Characterization of human fetal cord blood steroid profiles in relation to fetal sex and mode of delivery using temperature-dependent inclusion chromatography and principal component analysis (PCA).

    Science.gov (United States)

    Clifton, Vicki L; Bisits, Andrew; Zarzycki, Paweł K

    2007-08-15

    In the present work, human male and female fetal cord blood samples were purified, selectively extracted and separated to examine a fraction of steroids ranging from polar estetrol to relatively non-polar progesterone using solid phase extraction based on C-18 tubes and beta-cyclodextrin driven temperature dependent inclusion chromatography. Resulting UV diode array chromatographic patterns revealed the presence of 27 peaks. Chromatographic patterns of UV detected steroids were analyzed using principal components analysis which revealed differences between male/female and labour/not-in-labour clusters. Quantitative analysis of nine identified steroids including: estetrol, 17beta-estradiol, estrone, estriol, cortisol, cortisone, progesterone, 20 alpha-hydroxyprogesterone and 17 alpha-hydroxyprogesterone were not significantly different between males and females. Significant differences between male and female fetuses were related to as yet unidentified compounds. Four peaks were significantly different with labour which corresponded with cortisol, cortisone and two unidentified compounds. This protocol may distinguish significant differences between clinical groups that are not readily identifiable using univariate measurements of single steroids or different low molecular mass biomarkers. Moreover, we have provided new evidence that despite the absence of testosterone there are number of steroids and low molecular mass compounds that differ between male and female fetuses.

  5. Biologic and physical characteristics of the non-peptidic, non-digitalis-like natriuretic hormone.

    Science.gov (United States)

    Bricker, N S; Zea, L; Shapiro, M; Sanclemente, E; Shankel, S

    1993-11-01

    At least three independent groups of natriuretic hormones have been isolated over the past ten years. Two, atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP), are proteins and the third is made up of digitalis-like substances (DLS). The present report concerns the isolation, substantial purification and biologic actions of an entirely different natriuretic hormone (NH) which appears to be steroidal in nature and an isomer of cortisone. The source of NH was uremic urine. Purification involved successive chromatographic steps including gel filtration and multiple HPLC runs through C-18 resins. A translucent crystal ultimately was obtained. The product was examined using mass spectroscopy with trimethylsilyl derivatization. Only one compound was identifiable. The characteristics of the molecule include: a molecular weight, 360.4; a molecular formula, C21H28O5; a steroidal nucleus; UV absorption at 220 and 290 nm; and intrinsic fluorescence. The onset of action occurs within minutes both in the rat and, as previously shown, in several in vitro systems including the frog skin, toad bladder, fibroblasts and renal tubular epithelial cells grown in culture and isolated perfused cortical collecting tubules. In contrast to DLS, NH has been previously shown not to cross react with digoxin antibodies. Moreover, when given to intact rats, it produces a profound natriuresis but little or no kaliuresis. In contrast to ANF and BNP the compound is active orally as well as intravenously. It is clearly different from cortisone, based both on its biologic and mass spectroscopic characteristics.

  6. Capillary electrophoresis with UV detection and mass spectrometry in method development for profiling metabolites of steroid hormone metabolism.

    Science.gov (United States)

    Sirén, Heli; Seppänen-Laakso, Tuulikki; Oresic, Matej

    2008-08-15

    The aim of this study was to develop a method for comprehensive profiling of metabolites involved in mammalian steroid metabolism. The study was performed using the partial filling micellar electrokinetic chromatography (PF-MEKC) technique for determination of endogenous low-hydrophilic steroids. The detection techniques in capillary electrophoresis were UV absorption and electrospray mass spectrometry (ESI-MS). Thirteen steroids were included in the method development, and the selected were metabolites involved in major pathways of steroid biosynthesis. Although only eight of them could be separated and detected with UV, they could be identified by ESI-MS using selected ion monitoring (SIM) technique. Tandem MS spectra were also collected. UV detection was more sensitive than MS due to better separation of compounds and the selective signal sensitivity. The lowest limits of detection were 10-100 ng/mL for cortisone, corticosterone, hydrocortisone and testosterone. The other steroids could be detected at 500-1000 ng/mL. The identification of cortisone, corticosterone, hydrocortisone, estrogen and testosterone were made in patient urine samples and their concentrations were 1-40 microg/L.

  7. Changing glucocorticoid action: 11β-hydroxysteroid dehydrogenase type 1 in acute and chronic inflammation.

    Science.gov (United States)

    Chapman, Karen E; Coutinho, Agnes E; Zhang, Zhenguang; Kipari, Tiina; Savill, John S; Seckl, Jonathan R

    2013-09-01

    Since the discovery of cortisone in the 1940s and its early success in treatment of rheumatoid arthritis, glucocorticoids have remained the mainstay of anti-inflammatory therapies. However, cortisone itself is intrinsically inert. To be effective, it requires conversion to cortisol, the active glucocorticoid, by the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). Despite the identification of 11β-HSD in liver in 1953 (which we now know to be 11β-HSD1), its physiological role has been little explored until recently. Over the past decade, however, it has become apparent that 11β-HSD1 plays an important role in shaping endogenous glucocorticoid action. Acute inflammation is more severe with 11β-HSD1-deficiency or inhibition, yet in some inflammatory settings such as obesity or diabetes, 11β-HSD1-deficiency/inhibition is beneficial, reducing inflammation. Current evidence suggests both beneficial and detrimental effects may result from 11β-HSD1 inhibition in chronic inflammatory disease. Here we review recent evidence pertaining to the role of 11β-HSD1 in inflammation. This article is part of a Special Issue entitled 'CSR 2013'.

  8. [The development of adrenal cortical hormones into drugs].

    Science.gov (United States)

    Hansen, Sven Erik

    2008-01-01

    The interplay of factors contributing to the development of adrenal cortical hormones into drugs is reviewed. Clinical research performed during long periods by the physicians T. Addison and P.S. Hench in a nearly obsessional way stimulated basic research in physiology and biochemistry of the adrenal glands. From about 1900 increasing public interest in the "new hormones"coincided with expansion in research and development in academic and industrial settings. Pharmaceutical companies developed skill by production of much demanded organ-extracts, both effective ones as insulin and preparations of questionable clinical value. In 1949 the powerful anti-inflammatory effect of the cortical hormone, cortisone was discovered. As the supply of that hormone was scanty, it had temporarily to be substituted by the adrenocorticotropic hormone (ACTH) from animal hypophyses. Thereafter development accelerated through the combined effect of many years' painstaking research on the adrenal cortical hormones, technological breakthroughs, a climate positive for bold clinical experimentation and vigorous competition among mainly American pharmaceutical companies. Within a decade prednisone, the successor of cortisone, was launched, its clinical use established and large-scale inexpensive production instituted.

  9. [Treatment of severe Rhesus erythroblastosis].

    Science.gov (United States)

    Bichler, A; Frisch, H

    1977-01-01

    Report about the management of cases of severe Rhesus erythroblastosis. One case is specially discussed because of it's actuality. This was a patient with severe Rh-sensitization (OOD at 450 mm from the beginning of the 30th week of gestation in zone III according to Liley). Because of the haemolytic disease and the chronic fetal distress the Caesarean section was already performed in the 32nd week of gestation after Betamethason treatment of the mother. The Lecithin-Sphingomyelin (L/S) ratio in the amniotic fluid as a criterium of fetal lung maturity raised almost twicefold (from 0.9 to 1.6) after Cortison treatment. The intensive care (assisted ventilation with PEEP, correction of the acidosis and transfusion of packed red cells) of the severely anaemic (Hb 3.5 g%, Hk 15 vol.%) and hydropic newborn was already started in the delivery room. The newborn developed no RDS and was discharged healthy. With reference to this and other cases the management of severe Rh-sensitization before the 34th week of gestation is discussed. Premature infants are mainly susceptable to the development of a Respiratory Distress syndrome (RDS). After antepartum Cortison treatment for prevention of an RDS the date of confinement should be arranged earlier. The value of an early Caesarian section after antepartum Glucocorticoid treatment as compared to the application of intrauterine transfusions in cases of severe erythroblastosis is discussed. It is also reported about recent methods of treatment of severe conditions of hydrops fetalis.

  10. Changing glucocorticoid action: 11β-Hydroxysteroid dehydrogenase type 1 in acute and chronic inflammation

    Science.gov (United States)

    Chapman, Karen E.; Coutinho, Agnes E.; Zhang, Zhenguang; Kipari, Tiina; Savill, John S.; Seckl, Jonathan R.

    2013-01-01

    Since the discovery of cortisone in the 1940s and its early success in treatment of rheumatoid arthritis, glucocorticoids have remained the mainstay of anti-inflammatory therapies. However, cortisone itself is intrinsically inert. To be effective, it requires conversion to cortisol, the active glucocorticoid, by the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). Despite the identification of 11β-HSD in liver in 1953 (which we now know to be 11β-HSD1), its physiological role has been little explored until recently. Over the past decade, however, it has become apparent that 11β-HSD1 plays an important role in shaping endogenous glucocorticoid action. Acute inflammation is more severe with 11β-HSD1-deficiency or inhibition, yet in some inflammatory settings such as obesity or diabetes, 11β-HSD1-deficiency/inhibition is beneficial, reducing inflammation. Current evidence suggests both beneficial and detrimental effects may result from 11β-HSD1 inhibition in chronic inflammatory disease. Here we review recent evidence pertaining to the role of 11β-HSD1 in inflammation. This article is part of a Special Issue entitled ‘CSR 2013’. PMID:23435016

  11. Increased in vivo regeneration of cortisol in adipose tissue in human obesity and effects of the 11beta-hydroxysteroid dehydrogenase type 1 inhibitor carbenoxolone.

    Science.gov (United States)

    Sandeep, Thekkepat C; Andrew, Ruth; Homer, Natalie Z M; Andrews, Robert C; Smith, Ken; Walker, Brian R

    2005-03-01

    11beta-Hydroxysteroid dehydrogenase type 1 (11HSD1) regenerates cortisol from cortisone within adipose tissue and liver. 11HSD1 inhibitors may enhance insulin sensitivity in type 2 diabetes and be most efficacious in obesity when 11HSD1 is increased in subcutaneous adipose biopsies. We examined the regeneration of cortisol in vivo in obesity, and the effects of the 11HSD1 inhibitor carbenoxolone. We compared six lean and six obese men and performed a randomized, placebo-controlled crossover study of carbenoxolone in obese men. The obese men had no difference in their whole-body rate of regenerating cortisol (measured with 9,11,12,12-[(2)H(4)]cortisol tracer), but had more rapid conversion of [(3)H]cortisone to [(3)H]cortisol in abdominal subcutaneous adipose tissue (measured with microdialysis). During insulin infusion, adipose 11HSD1 activity fell markedly in lean but not in obese men. Carbenoxolone inhibited whole-body cortisol regeneration, but did not significantly inhibit adipose 11HSD1 and had no effects on insulin sensitivity (measured by [(2)H(2)]glucose infusion with or without hyperinsulinemia). Thus, in vivo cortisol generation is increased selectively within adipose tissue in obesity, perhaps reflecting resistance to insulin-mediated downregulation of 11HSD1. However, obese men are less susceptible than lean men to the insulin-sensitizing effects of carbenoxolone. To be useful in obese patients, 11HSD1 inhibitors will need to inhibit the enzyme more effectively in adipose tissue.

  12. Regulation of lipogenesis by glucocorticoids and insulin in human adipose tissue.

    Science.gov (United States)

    Gathercole, Laura L; Morgan, Stuart A; Bujalska, Iwona J; Hauton, David; Stewart, Paul M; Tomlinson, Jeremy W

    2011-01-01

    Patients with glucocorticoid (GC) excess, Cushing's syndrome, develop a classic phenotype characterized by central obesity and insulin resistance. GCs are known to increase the release of fatty acids from adipose, by stimulating lipolysis, however, the impact of GCs on the processes that regulate lipid accumulation has not been explored. Intracellular levels of active GC are dependent upon the activity of 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) and we have hypothesized that 11β-HSD1 activity can regulate lipid homeostasis in human adipose tissue (Chub-S7 cell line and primary cultures of human subcutaneous (sc) and omental (om) adipocytes. Across adipocyte differentiation, lipogenesis increased whilst β-oxidation decreased. GC treatment decreased lipogenesis but did not alter rates of β-oxidation in Chub-S7 cells, whilst insulin increased lipogenesis in all adipocyte cell models. Low dose Dexamethasone pre-treatment (5 nM) of Chub-S7 cells augmented the ability of insulin to stimulate lipogenesis and there was no evidence of adipose tissue insulin resistance in primary sc cells. Both cortisol and cortisone decreased lipogenesis; selective 11β-HSD1 inhibition completely abolished cortisone-mediated repression of lipogenesis. GCs have potent actions upon lipid homeostasis and these effects are dependent upon interactions with insulin. These in vitro data suggest that manipulation of GC availability through selective 11β-HSD1 inhibition modifies lipid homeostasis in human adipocytes.

  13. The effect of cortisol in rat steatotic and non-steatotic liver transplantation from brain-dead donors.

    Science.gov (United States)

    Jiménez-Castro, Mónica B; Negrete-Sánchez, Elsa; Casillas-Ramírez, Araní; Gulfo, Jose; Álvarez-Mercado, Ana I; Cornide-Petronio, María Eugenia; Gracia-Sancho, Jordi; Rodés, Juan; Peralta, Carmen

    2017-04-25

    In the present study, we examined the effects of cortisol on steatotic and non-steatotic liver grafts from brain-dead donors and characterized the underlying mechanisms involved. Non-steatotic liver grafts showed reduced cortisol and increased cortisone levels in association with up-regulation of enzymes that inactivate cortisol. Conversely, steatotic liver grafts exhibited increased cortisol and reduced cortisone levels. The enzymes involved in cortisol generation were overexpressed, and those involved in cortisol inactivation or clearance were down-regulated in steatotic liver grafts. Exogenous administration of cortisol negatively affected hepatic damage and survival rate in non-steatotic liver transplantation (LT); however, cortisol treatment up-regulated the phosphoinositide 3-kinase (PI3K)-protein kinase C (PKC) pathway, resulting in protection against the deleterious effects of brain-dead donors on damage and inflammatory response in steatotic LT as well as in increased survival of recipients. The present study highlights the differences in the role of cortisol and hepatic mechanisms that regulate cortisol levels based on the type of liver. Our findings suggest that cortisol treatment is a feasible and highly protective strategy to reduce the adverse effects of brain-dead donor livers in order to ultimately improve liver graft quality in the presence of steatosis, whereas cortisol treatment would not be recommended for non-steatotic liver grafts. © 2017 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

  14. Modulation of GR activity does not affect the in vitro metabolism of cortisol by rainbow trout ovarian follicles.

    Science.gov (United States)

    Li, Mao; Christie, Heather; Leatherland, John

    2014-12-01

    The goal of the study was to determine whether the metabolic clearance of cortisol from rainbow trout (Oncorhynchus mykiss) ovarian follicles is affected by the level of ovarian steroidogenesis, and whether it involves the activation of glucocorticoid receptors (GRs). Ovarian follicles were incubated in vitro; the adenylate cyclase activator, forskolin, was used to stimulate ovarian steroidogenesis, and the modulation of GR activity was brought about using GR agonists (cortisol and dexamethasone) or the GR antagonist, mifepristone (RU486). The follicles were co-incubated with [2, 4, 6, 7 (3)H] cortisol, and the tritium-labelled steroid products were separated by HPLC. In addition, the rates of expression of genes encoding for the two forms of GR (gr1 and gr2) were measured. Cortisone, cortisol sulphate, and cortisone sulphate were the major glucocorticoid products of cortisol metabolism, indicative of the action of 11β-hydroxysteroid dehydrogenase and glucocorticoid sulphotransferase in the follicular cells. There were no effects of RU486 or forskolin on the rates of [(3)H]cortisol metabolism suggesting that cortisol metabolism by ovarian follicles was independent of GR activation, and not influenced by increased activation of gonadal reproductive steroidogenesis.

  15. Regulation of lipogenesis by glucocorticoids and insulin in human adipose tissue.

    Directory of Open Access Journals (Sweden)

    Laura L Gathercole

    Full Text Available Patients with glucocorticoid (GC excess, Cushing's syndrome, develop a classic phenotype characterized by central obesity and insulin resistance. GCs are known to increase the release of fatty acids from adipose, by stimulating lipolysis, however, the impact of GCs on the processes that regulate lipid accumulation has not been explored. Intracellular levels of active GC are dependent upon the activity of 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1 and we have hypothesized that 11β-HSD1 activity can regulate lipid homeostasis in human adipose tissue (Chub-S7 cell line and primary cultures of human subcutaneous (sc and omental (om adipocytes. Across adipocyte differentiation, lipogenesis increased whilst β-oxidation decreased. GC treatment decreased lipogenesis but did not alter rates of β-oxidation in Chub-S7 cells, whilst insulin increased lipogenesis in all adipocyte cell models. Low dose Dexamethasone pre-treatment (5 nM of Chub-S7 cells augmented the ability of insulin to stimulate lipogenesis and there was no evidence of adipose tissue insulin resistance in primary sc cells. Both cortisol and cortisone decreased lipogenesis; selective 11β-HSD1 inhibition completely abolished cortisone-mediated repression of lipogenesis. GCs have potent actions upon lipid homeostasis and these effects are dependent upon interactions with insulin. These in vitro data suggest that manipulation of GC availability through selective 11β-HSD1 inhibition modifies lipid homeostasis in human adipocytes.

  16. Autologous Blood Injection and Wrist Immobilisation for Chronic Lateral Epicondylitis

    Directory of Open Access Journals (Sweden)

    Nicola Massy-Westropp

    2012-01-01

    Full Text Available Purpose. This study explored the effect of autologous blood injection (with ultrasound guidance to the elbows of patients who had radiologically assessed degeneration of the origin of extensor carpi radialis brevis and failed cortisone injection/s to the lateral epicondylitis. Methods. This prospective longitudinal series involved preinjection assessment of pain, grip strength, and function, using the patient-rated tennis elbow evaluation. Patients were injected with blood from the contralateral limb and then wore a customised wrist support for five days, after which they commenced a stretching, strengthening, and massage programme with an occupational therapist. These patients were assessed after six months and then finally between 18 months and five years after injection, using the patient-rated tennis elbow evaluation. Results. Thirty-eight of 40 patients completed the study, showing significant improvement in pain; the worst pain decreased by two to five points out of a 10-point visual analogue for pain. Self-perceived function improved by 11–25 points out of 100. Women showed significant increase in grip, but men did not. Conclusions. Autologous blood injection improved pain and function in a worker’s compensation cohort of patients with chronic lateral epicondylitis, who had not had relief with cortisone injection.

  17. Anti-inflammatory effects of levalbuterol-induced 11β-hydroxysteroid dehydrogenase type 1 activity in airway epithelial cells

    Directory of Open Access Journals (Sweden)

    Matthew J Randall

    2015-01-01

    Full Text Available Airway epithelial NF-kB activation is observed in asthmatic subjects and is a cause of airway inflammation in mouse models of allergic asthma. Combination therapy with inhaled short-acting b2-agonists and corticosteroids significantly improves lung function and reduces inflammation in asthmatic subjects. Corticosteroids operate through a number of mechanisms to potently inhibit NF-kB activity. Since b-agonists can induce expression of 11b-HSD1, which converts inactive 11-keto corticosteroids into active 11-hydroxy corticosteroids, thereby potentiating the effects of endogenous glucocorticoids, we examined whether this mechanism is involved in the inhibition of NF-kB activation induced by the b-agonist albuterol in airway epithelial cells. Treatment of transformed murine Club cells (MTCC with (R-albuterol (levalbuterol, but not with (S- or a mixture of (R+S- (racemic albuterol, augmented mRNA expression of 11b-HSD1. MTCC were stably transfected with luciferase (luc reporter constructs under transcriptional regulation by NF-kB (NF-kB/luc or glucocorticoid response element (GRE/luc consensus motifs. Stimulation of NF-kB/luc MTCC with lipopolysaccharide (LPS or tumor necrosis factor-α (TNFα induced luciferase activity, which was inhibited by pretreatment with (R-, but not (S- or racemic albuterol. Furthermore, pretreatment of GRE/luc MTCC with (R-albuterol augmented 11-keto corticosteroid (cortisone induced luciferase activity, which was diminished by the 11β-HSD inhibitor glycyrrhetinic acid (18β-GA. LPS- and TNFα-induced NF-kB/luc activity was diminished in MTCC cells treated with a combination of cortisone and (R-albuterol, an effect that was inhibited by 18β-GA. Finally, pretreatment of MTCC cells with the combination of cortisone and (R-albuterol diminished LPS- and TNFα-induced pro-inflammatory cytokine production. These results demonstrate that levalbuterol augments conversion of inactive 11-keto corticosteroids into the active 11

  18. Protease-mediated enhancement of lymphocyte-induced angiogenesis in X-ray irradiated mice

    Energy Technology Data Exchange (ETDEWEB)

    Kaminski, M.J.; Majewski, S.; Kaminska, G.; Bem, W.; Szmurlo, A. (Akademia Medyczna, Warsaw (Poland). Zaklad Histologii i Embriologii)

    1983-02-01

    Angiogenesis was induced in mice by intradermal injection of semi-syngeneic splenocytes, and after three days the number of newly formed blood vessels at the injection site was counted. When recipients were total-body irradiated with 700 R 2 hours before the lymphocyte injection, the angiogenesis was significantly higher than in non-irradiated mice. The angiogenesis enhancement was of a systemic (not local) character as revealed in experiments with shielding of irradiated animals. This enhancement was not due to X-ray dependent immunosuppression, as shown in experiments with non-irradiated, pharmacologically immunosuppressed mice. Decreased angiogenesis was observed in irradiated mice after treatment with cortisone acetate, aprotinin, and EACA. The results suggest that proteases might be involved in mediating the angiogenesis enhancement after X-irradiation.

  19. Diffused suberitrodermic psoriasis induced by infliximab

    Directory of Open Access Journals (Sweden)

    V. Bruzzese

    2011-09-01

    Full Text Available The case of a young male is described, affected by Crohn disease with reactive Spondoloarthritis essay with Infliximab to the dose of 3 mg/kgs. After 15 days from the 3° infusion, the patient developed a first psoriasic eruption to the palm of the hands and the plant of the feet, for which was begun topical therapy with cortisone. After an initial improvement, the patient introduced a diffusion of the psoriasic eruption to the whole trunk and the limbs with a suberitrodermic aspect. The possible pathogenesis of this paradoxical effect of the anti-TNF is considered. Also being still partly the causes, is important the inhibition of the TNF-alpha with consequent expansion of the INF-alpha, in tum potential inductor of psoriasis.

  20. Informative value of some endocrine homeostatic parameters in the formation of endometrial cancer risk groups

    Directory of Open Access Journals (Sweden)

    Yu. S. Sidorenko

    2012-01-01

    Full Text Available Twenty-five patients with atypical endometrial hyperplasia (AEH and 90 patients with Stages I-II endometrial cancer (EC were followed up. The patients’ mean age was 44.3±2.1 years. A control group consisted of 20 healthy women matched for age. Before treatment, the authors determined the blood levels of adrenocorticotropic hormone and cortisol by radiometric assay and the content of daily excreted cortisol, cortisone, tetrahydrocortisol, tetrahydrocortisone, 11-hydroxy-17-ketosteroids, estrone, estradiol, and pregnanediol by the conventional classical studies.The nature of the impaired synthesis and metabolism of sex and adrenocorticoid hormones and their degree have been found to coincide, which suggest that it is expedient to use these findings to form EC risk groups in patients with AEH in the late reproductive period.

  1. Effect of undernutrition and hormone treatments on the absorption of proteins in suckling rat intestine

    Energy Technology Data Exchange (ETDEWEB)

    Babbar, H.S.; Jaswal, V.M.; Mahmood, A. (Panjab Univ., Chandigarh (India))

    1990-02-01

    The absorption of {sup 125}I-labeled BSA and gamma-globulin was significantly (P less than 0.01) elevated in UN pups compared to the controls. Administration of pharmacological doses of cortisone, thyroxine, and insulin markedly (P less than 0.001) reduced the absorption of BSA and gamma-globulin in UN pups. There was no significant difference in the binding of {sup 125}I-labeled BSA and gamma-globulin to microvillus membrane in the control and experimental animals. However, the degradation of labeled BSA and gamma-globulin by luminal content was considerably higher (55-70%) in controls compared to UN pups. This suggested that observed increase in the absorption of proteins in nutritionally deprived pups was unrelated to their binding to the microvillus surface but presumably it is a consequence of reduced luminal degradation together with delayed maturational development as suggested by the pattern of brush border enzymes in the UN intestinal tissue.

  2. short history of anti-rheumatic therapy. IV. Corticosteroids

    Directory of Open Access Journals (Sweden)

    P. Marson

    2011-06-01

    Full Text Available In 1948 a corticosteroid compound was administered for the first time to a patient affected by rheumatoid arthritis by Philip Showalter Hench, a rheumatologist at the Mayo Clinic in Rochester, Minnesota (USA. He was investigating since 1929 the role of adrenal gland-derived substances in rheumatoid arthritis. For the discovery of cortisone and its applications in anti-rheumatic therapy, Hench, along with Edward Calvin Kendall and Tadeusz Reichstein, won the 1950 Nobel Prize for Medicine. In this review we summarize the main stages that led to the identification of the so-called compound E, which was used by Hench. We also consider the subsequent development of steroid therapy in rheumatic diseases, through the introduction of new molecules with less mineralocorticoid effects, such as prednisone, and more recently, deflazacort.

  3. Glucocorticoid receptors in murine erythroleukaemic cells

    Energy Technology Data Exchange (ETDEWEB)

    Hammond, K.D.; Torrance, J.M.; DiDomenico, M.

    1987-01-01

    Glucocorticoid receptors in murine erythroleukaemic cells were studied in relation to hexamethylene bisacetamide (HMBA) induced differentiation. Specific binding of dexamethasone was measured. A single class of saturable, high affinity binding sites was demonstrated in intact cells; with cell homogenates or fractions binding was low and could not be reliably quantified. Receptor binding in whole cell suspensions was lower in cells which had been treated with HMBA (36.5 +/- 8.2 pmol/g protein) than in untreated controls (87.9 +/- 23.6 pmol/g protein); dissociation constants were similar in treated (2.7 nM) and untreated cells (2.5 nM). Dexamethasone, hydrocortisone, corticosterone and progesterone competed with tritium-labelled dexamethasone for receptor binding sites; cortisone, deoxycorticosterone and oestradiol had little effect.

  4. Radiotherapy of endocrine ophthalmopathy. Evaluation of 56 case records

    Energy Technology Data Exchange (ETDEWEB)

    Uhlenbrock, D.; Fischer, H.J.; Rohwerder, R.

    1984-08-01

    The authors present the radiotherapeutic results achieved in 56 patients with endocrine ophthalmopathy, 15 out of them with severe, so-called malignant course. All patients were irradiated conventionally with small doses between 3 and 10 Gy at the surface. For this purpose, a deep therapy unit with 250 kV was used. The X-ray irradiation produced an improvement in 62% of the cases; the separate evaluation of cases with malignant course showed an improvement in nine cases. Thus the results produced by this method are as good as those of high doses, the greater possibilities in case of recurrence, however, are to be considered as an advantage. The irradiation should be applied early, and the simultaneous administration of a cortisone preparation is preferred by our team.

  5. The place of imaging in exploration of the adrenal glands. Place de l'imagerie dans l'exploration des surrenales

    Energy Technology Data Exchange (ETDEWEB)

    Cyteval, C.; Pradel, J.; Pujol, J.; Lamarque, J.L.; Jaffiol, C. (Hopital Lapeyronie, 34 - Montpellier (FR)); Krempf, M.; Charbonnel, B. (Hotel Dieu, 44 - Nantes (FR)); Peltier, P.; Chatal, J.F. (Centre Regional de Lutte contre le Cancer Rene-Gauducheau, 44 - Nantes (FR))

    1990-01-01

    Currently, the major method of adrenal gland imaging is computed tomography. This method allows demonstration of normal adrenals and the diagnosis of adrenal masses (if these are greater than 1 cm in diameter). The examination should be directed by clinical signs and known laboratory investigations. Computed tomography is therefore the first line investigation to perform. Certain lesions may be better demonstrated by other methods: MRI and MIBG scintigraphy offer a greater specificity in the investigation of pheochromocytomas. In addition, scintigraphy can identify possible ectopic tumours or recurrences. - Selective catheterisation of the adrenal veins allows aldosterone and cortisone secretions to be assayed. There remains the problem of the incidental finding of adrenal masses in either an asymptomatic patient or in the context of investigation of spread of a known cancer. These lesions may benefit from diagnostic percutaneous guided biopsy.

  6. MISE AU POINT D'UN MODELE EXPERIMENTAL D'ASPERGILLOSE PULMONAIRE CHEZ LA SOURIS

    Directory of Open Access Journals (Sweden)

    M AISSI

    2003-06-01

    Full Text Available Aspergillus fumigatus est le principal agent causal des aspergilloses humaines dont la forme la plus grave est l'aspergillose pulmonaire invasive très fréquente chez des sujets fortement imunodéprimés, Nous avons donc tenté de mettre au point un modèle expérimental d'aspergillose pulmonaire invasive chez la souris se rapprochant le plus des conditions naturelles d'infestation, ce qui nous permettra d'étudier le développement in vivo de ce champignon. Le modèle expérimental que nous avons mis au point est réalisé par dépôt d'une suspension de spores sur les narines de l'animal immunodéprimé par administration quotidienne d'acétate de cortisone.

  7. Data related to inflammation and cholesterol deposition triggered by macrophages exposition to modified LDL

    Directory of Open Access Journals (Sweden)

    Juan Toledo

    2016-09-01

    Full Text Available This article supports experimental evidence on the time-dependent effect on gene expression related to inflammation and cholesterol deposition in lipid-loaded cells. The cells employed were human monocytes THP1 line transformed into macrophages by treatment with phorbol esters. Macrophages were treated at different times with oxidized low density lipoprotein (Ox-LDL and then gene expression was measured. We also include data about the different types of oxidized lipoprotein obtained (low, media or high oxidation for differential exposure with Cu ions. These data include characterization to lipid and protein peroxidative damage and also quantification of cell viability by exposure to native and modified LDL. The present article complements data published in “Decreased OxLDL uptake and cholesterol efflux in THP1 cells elicited by cortisol and by cortisone through 11β-hydroxysteroid dehydrogenase type 1” Ledda et al. (in press [1].

  8. The diagnosis of Pneumocystis Carinii pneumonia by new laboratory methods

    Directory of Open Access Journals (Sweden)

    Rahimifard N

    1999-09-01

    Full Text Available The object of this study was to find a suitable staining method for P.carinii. This parasite is not easily stained and clinical signs are not specific for the diagnosis of P.carinii pneumonia and therefore optimal laboratory methods for observing the organism are extremely valuable. In all 17 new conventional and modified staining techniques were used on lung impression smears and tissue section of sprague Dawley Rat treated with cortisone. Of these methods modified methylene blue 1 & 2, modified cresy violet 1, 2, 3, 4 modified Gram, modified Giemsa 2 and modified Griedley techniques have not previously been reported. After comparing readability of the slides, ease of performances, rapidity, availability and sensitivity of these 17 techniques for the diagnosis of P.carinii pneumonia, modified toluidine blue 01 & 2, modified methylene blue 1 & 2 and modified cresyl violet 3, 4 are suggested as the methods of choice for the rapid diagnosis of P.carinii pneumonia.

  9. Development and X-ray morphology of amiodarone pneumopathy. Die Entwicklung und Roentgenmorphologie der Amiodaronpneumopathie

    Energy Technology Data Exchange (ETDEWEB)

    Billmann, P. (Kreiskrankenhaus Lahr (Germany, F.R.). Radiologisches Inst.); Fleischmann, D. (Kreiskrankenhaus Lahr (Germany, F.R.). Kardiologische Klinik); Baumeister, L. (Sankt-Josefs-Krankenhaus, Offenburg am Main (Germany, F.R.). Radiologische Abt.)

    1991-04-01

    Besides general extracardiac physical side effects, the antiarrhythmic amiodarone hydrochloride gives rise to morphologically manifest organ changes. Pneumopathy has been reported in up to 8% of the patients treated with this preparation. Radiologically and histologically, the clinical picture can resemble that of exogenous allergic alveolitis. When the course is protracted there is interstitial fibrotic degeneration of the pulmonary parenchyma with a corresponding morphological correlate in the X-ray. The extent to which the changes observed result from dose-dependent toxicity of amiodarone has not been completely elucidated even now, since pulmonary changes suggestive of an immune process can occur even at low doses. When there is reason suspect the presence of amiodarone pneumopathy, the preparation should be discontinued. Radiological and clinical findings generally regress with cortisone treatment. (orig.).

  10. High-performance liquid chromatographic (HPLC) separation and quantitation of endogenous glucocorticoids after solid-phase extraction from plasma.

    Science.gov (United States)

    Dawson, R; Kontur, P; Monjan, A

    1984-01-01

    This study describes a method for the extraction and simultaneous measurement of cortisone, cortisol and corticosterone using dexamethasone as an internal standard. Solid-phase extraction of plasma steroids with C18 columns allows the samples to be extracted, washed and concentrated in a single step with minimal sample handling and without the use of large volumes of organic solvents. HPLC separation of the steroids is accomplished within 10 min and the individual steroid peaks are quantitated by UV detection at 239 nm. This assay was examined for linearity, extraction efficiency, precision and potential interference by commonly used drugs. Plasma values of glucocorticoids are reported for samples obtained from human subjects as well as from rats. HPLC was also compared to RIA for the determination of plasma levels of corticosterone in the rat. Solid-phase extraction and assay by HPLC provides a rapid and specific method for the simultaneous determination of plasma glucocorticoids.

  11. Comparison of the use of anionic and cationic surfactants for the separation of steroids based on MEKC and sweeping-MEKC modes.

    Science.gov (United States)

    Shen, Hui-Ju; Lin, Cheng-Huang

    2006-03-01

    In attempts to improve the selectivity and sensitivity of steroid separation and to determine their migration order, a comparison of the use of anionic and cationic surfactants based on the MEKC and sweeping-MEKC modes was made. A mixture of six steroids (progesterone, 17-hydroxy progesterone, 11-deoxycortisol, corticosterone, cortisone, and cortisol) could be separated and detected by means of the CE/UV-absorption method. The order of migration time for these steroids was compared under various conditions, including acidic/alkaline buffers, anionic/cationic surfactants, and positive/negative applied voltage, causing the direction of the EOF and the migration of micelles to change. The major rules for generally predicting the migration order of steroids are summarized. The detection limits were significantly improved when the sweeping-MEKC mode was applied.

  12. Simultaneous determination of methylparaben, propylparaben, hydrocortisone acetate and its degradation products in a topical cream by RP-HPLC.

    Science.gov (United States)

    Hájková, R; Solich, P; Dvorák, J; Sícha, J

    2003-08-08

    A novel reversed-phase high-performance liquid chromatographic method with UV spectrophotometric detection was developed and validated for the determination of compounds in topical cream. The method describes determination of active component hydrocortisone acetate (HCA), its degradation products hydrocortisone (HC) and cortisone acetate (occurring in formulation after long-term stability tests) and two preservatives presented in the cream-methylparaben and propylparaben, using dexamethasone as an internal standard. The chromatographic separation was performed on a 5 microm SUPELCO Discovery C18 125 x 4-mm ID column. The optimised mobile phase for separation of all the compounds consists of methanol, acetonitrile and water (15:27:58, v/v/v), with the analysis time less than 13 min. The method was applicable for routine analysis (assays and stability tests) of active compound HCA, preservatives and degradation products in pharmaceutical product--topical cream Hydrocortizone cream 1%.

  13. Determination of adrenal steroids by microfluidic chip using micellar electrokinetic chromatography.

    Science.gov (United States)

    Shen, Shuanglong; Li, Yan; Wakida, Shin-ichi; Takeda, Sahori

    2009-06-01

    This paper describes a sensitive and convenient method to separate progesterone, 17alpha-hydroxy progesterone, cortexolone, hydrocortisone and cortisone, all of which are steroids and have similar structures, using microfluidic chip-based technology with UV detection at 252 nm. We successfully obtained high-speed separation of the five steroids within 70 s in optimized microfluidic controls and micellar electrokinetic chromatography (MEKC) separation conditions. Fairly good linearity with correlation coefficient of over 0.98 from 10 or 20 to 100 mg/l steroid chemicals was obtained. The limits of detection obtained at a signal to noise ratio of 3 were from 3.89 to 7.80 mg/l. The values of the relative standard deviation (RSD) were 0.98-1.34% for repetitive injection (n = 12) and the intraday and interday RSDs were below 6%. The highly stable response reflected the feasibility of this method.

  14. Effect of Food, Diet and Nutrition on Military Readiness and Preparedness of Army Personnel and Dependents in a Peacetime Environment.

    Science.gov (United States)

    1991-08-15

    0 0 0 0 0 0 0 0 0l 0I ~) 0 UV - C)~ F- - N CQC IT/ W IOIlslL TIT 4- C\\2 m -0 0 Cil (1 0Jw V01lao " TIIO coN 7 El 0 U4 n C 0 0 .- 0 o U-~N...Exe rcise/arond he Relaxation arud~ Relaxation volr course (Croup A) volr course (Croup B) 10 oin uV -b aI308:00 p. 3Wo80 Opm 15 16 Jonu (ra Modified...37 1... ..3......9.... CORTISONE , PREDNISONE ACTH, PREDNISOLONE, DECAnRAN (Cortico- steroids)? 12. During the past year, have you been treated for any

  15. [Determination of benproperine phosphate tablets by high performance liquid chromatography].

    Science.gov (United States)

    Yang, X J; Yang, X Y

    2000-11-01

    A reversed-phase HPLC method for the determination of benproperine phosphate tablets is reported. The chromatographic conditions were Hypersil-C18 column(5 microns, 4.6 mm i.d. x 150 mm) at 35 degrees C, mobile phase of methanol-water-glacial acetic acid-triethylamine(60:35:5:0.1, V/V) with a flow rate of 0.9 mL/min and UV detection at 270 nm. Cortisone acetate was selected as the internal standard. The linear relationship of calibration curve was good in the range of 9.96 mg/L-49.8 mg/L(r = 0.9998). The average recovery and RSD were 99.91%(n = 5) and 0.43% respectively. The total time of analysis for a run was within 7 min. The method is simple, sensitive, rapid and accurate.

  16. Immobilized Enzymes/Bacteria for Naval Applications - Initial Data Base.

    Science.gov (United States)

    1981-05-31

    donor 1.2.1.9 Glyceraldehyde phosphate dehydro- genase 1. HCIdonor 1.3.1.3 Cortisone reductase 14C-12donor 1.4.3.4 Monoamine oxidase 1.5 C-NHI donor...Q)1 " H - 4 : 0- a)4 $4 0 , gwpua0(U , W 4J A 44 >US.40 $ C UV ) d.4 wo00-4 -A.OC 4) Q-- CO rI$ - 4 J4 0W 6 $ ,UO () Q G0 4-r4 " 4 w0 -400 -W C 0 -4b0... Uv EU :> .- -J 4J -L 0 > Z C. -0~0- r4 $00)4- U042 Q)-4CU CDUUU -~ 00 0. U) I~ ~ 4’ * 78 C) Co .4 0 0w 4j ;rj 4 0 -4-4 P.-1 U) 0 . 414 $4 -’ 0> 0 $4 w

  17. Evolution of corticosteroid specificity for human, chicken, alligator and frog glucocorticoid receptors.

    Science.gov (United States)

    Katsu, Yoshinao; Kohno, Satomi; Oka, Kaori; Baker, Michael E

    2016-09-01

    We investigated the evolution of the response of human, chicken, alligator and frog glucocorticoid receptors (GRs) to dexamethasone, cortisol, cortisone, corticosterone, 11-deoxycorticosterone, 11-deoxycortisol and aldosterone. We find significant differences among these vertebrates in the transcriptional activation of their full length GRs by these steroids, indicating that there were changes in the specificity of the GR for steroids during the evolution of terrestrial vertebrates. To begin to study the role of interactions between different domains on the GR in steroid sensitivity and specificity for terrestrial GRs, we investigated transcriptional activation of truncated GRs containing their hinge domain and ligand binding domain (LBD) fused to a GAL4 DNA binding domain (GAL4-DBD). Compared to corresponding full length GRs, transcriptional activation of GAL4-DBD_GR-hinge/LBD constructs required higher steroid concentrations and displayed altered steroid specificity, indicating that interactions between the hinge/LBD and other domains are important in glucocorticoid activation of these terrestrial GRs.

  18. Harvey Cushing: Cushing's disease.

    Science.gov (United States)

    Ellis, Harold

    2012-09-01

    In 1932 Harvey Cushing published an article entitled 'Basophil adenomas of the pituitary and their clinical manifestations'. These are rare tumours of the anterior pituitary gland, at the base of the brain, with striking manifestations, which include adiposity of the face and trunk, but not the limbs, weakness, fatigue, abdominal striae, facial hair, high blood pressure and raised blood sugar. Although I spent two years in an army neurosurgical unit, I never saw a case. More frequently, the same clinical picture is produced by a benign adenoma of the suprarenal cortex, but today by far the commonest cause of this condition is seen in the patient receiving high dosage of cortisone, when we talk about the person exhibiting 'Cushingoid features'. Most readers of this journal will have seen such cases.

  19. LATERAL EPICONDYLITIS OF THE ELBOW.

    Science.gov (United States)

    Cohen, Marcio; da Rocha Motta Filho, Geraldo

    2012-01-01

    Lateral epicondylitis, also known as tennis elbow, is a common condition that is estimated to affect 1% to 3% of the population. The word epicondylitis suggests inflammation, although histological analysis on the tissue fails to show any inflammatory process. The structure most commonly affected is the origin of the tendon of the extensor carpi radialis brevis and the mechanism of injury is associated with overloading. Nonsurgical treatment is the preferred method, and this includes rest, physiotherapy, cortisone infiltration, platelet-rich plasma injections and use of specific immobilization. Surgical treatment is recommended when functional disability and pain persist. Both the open and the arthroscopic surgical technique with resection of the degenerated tendon tissue present good results in the literature.

  20. An exploration of fluoroscopically guided spinal steroid injections in patients with non-specific exercise-related lower-limb pain

    Directory of Open Access Journals (Sweden)

    Leon Neve

    2010-09-01

    Full Text Available Leon Neve1, John Orchard2, Nathan Gibbs3, Willem van Mechelen4, Evert Verhagen4, Ken Sesel5, Ian Burgess6, Brett Hines61VU University, Amsterdam, The Netherlands; 2School of Public Health, University of Sydney, Sydney, NSW, Australia; 3South Sydney Sports Medicine, Sydney, NSW, Australia; 4EMGO, VU University, Amsterdam, The Netherlands; 5Sydney X-ray Centre, Sydney, NSW, Australia; 6Mater Imaging, Sydney, NSW, AustraliaBackground: Fluoroscopically guided lumbar cortisone injections have been proven useful in cases of lower-limb pain caused by lumbar disc prolapse (with evidence levels ll-1/ll-2. These injections are also sometimes used clinically in sports medicine for patients with non-specific exercise-related lower-limb pain, where no prolapse or other obvious cause of nerve-impingement is diagnosed via magnetic resonance imaging (MRI or computed tomography (CT, even though this treatment scenario has not been adequately studied for this last diagnosis.Objectives: To explore whether fluoroscopically guided transforaminal lumbar cortisone injections may be a valid treatment method for non-specific exercise-related lower-limb pain.Study design: Retrospective case series.Methods: Patients were selected from databases at two sports clinics and divided into two groups: Group D, with back-related lower-limb pain and disc prolapse proven on CT or MR; and Group N, with non-specific exercise-related lower-limb pain. Patients were sent a questionnaire regarding: symptoms, improvement, effect of injections, satisfaction, side effects and other used treatments. Outcomes were compared between Group D and N.Results: 153 patients were eligible for the study (Group D: 93/Group N: 60. Eventually 110 patients responded (Group D: 67/Group N: 43. Twelve percent of Group D and 14% of Group N indicated that the injections had fully cured their symptoms. Altogether, 27% of Group D and 24% of Group N were certain the injections had improved their symptoms in the

  1. Personality and coping strategies during submarine missions.

    Science.gov (United States)

    Sandal, Gro M; Endresen, Inger M; Vaernes, Ragnar; Ursin, Holger

    2003-01-01

    Relations between personality profiles, measured by the Personality Characteristics Inventory (PCI), and habitual coping strategies, measured by the Utrecht Coping List (UCL), were investigated in a sample of submarine personnel and office employees. The predictive validity of these instruments were examined for reported stress, health complaints, and salivary cortisone measures during 3 submarine missions. PCI and UCL were completed before the missions, and questionnaires and saliva were collected weekly. The results showed no significant relations between PCI profiles and coping strategies. Interpersonal orientation, achievement motivation, and habitual coping strategies were predictors for coping during the submarine missions. Problem-directed strategies and interpersonal sensitivity combined with strong achievement motivation were related to low indicated stress from social factors (lack of privacy, interpersonal tension, and crowding) and homesickness. The findings suggest that interpersonal characteristics need to be considered in the selection of submariners and personnel for other military settings in which units are exposed to prolonged stress and isolation.

  2. [Recurrent acute pericarditis and corticoid dependence. Apropos of 10 cases].

    Science.gov (United States)

    Godeau, P; Derrida, J P; Bletry, O; Herreman, G

    1975-10-09

    The authors report ten cases of acute recurrent pericarditis observed over a period of 5 years and emphasize the frequency of these relapses involving 15 to 20% of cases of acute pericarditis. Usually, no cause is found and, althrough an immunological mechanism has been suggested, there is no common test which may confirm or disprove this theory. The risk of ultimate constrictive pericarditis is minimal and this risk is thus not taken into consideration in deciding on treatment. On the other hand, the undesirable effects of corticosteroids which favour relapses, seem to be demonstrated. The use of corticosteroids in cases of acute pericarditis should thus be exceptional and one should prefer non-steroid anti-inflammatory drugs. Immunosuppressors and pericardectomy should be reserved for the rare forms where the disease progresses and relapses continue after cortisone has been stopped.

  3. [Plantar fibromatosis: therapy by total plantarfasciectomy].

    Science.gov (United States)

    Beckmann, J; Kalteis, T; Baer, W; Grifka, J; Lerch, K

    2004-01-01

    Morbus Ledderhose is a rare fibromatous disease of the plantar fascia. Clinical features include palpable solitary or multiple nodules and cords, mainly affecting the medial part of the plantar fascia. When clinical symptoms occur, conservative options include stretching, orthotics, nonsteroidal antirheumatic drugs, local cortisone-injections and physiotherapy. Operative treatment is indicated in case of persistent pain or if conservative measures fail. The standard procedure includes a partial fasciectomy of the plantar aponeurosis. There is a high recurrence rate with an increased risk of complications and more aggressive ingrowth into anatomical structures after partial resection. Therefore we recommend a complete fasciectomy not only in recurrent disease, but also as the primary procedure of choice.

  4. Chemical methods for the conversion of Prednisolone to 11--hydroxy-1,4-androstadiene-3,17-dione

    Indian Academy of Sciences (India)

    Pinnama Reddy Surya Pratap; Syed Shafi; Fatima Naaz; Nayakanti Devanna

    2015-10-01

    Several microbial transformations of steroids to 17-keto cortisones through side chain cleavage have been presented in the literature; however, yields and product selectivity in these methods were low. In the present study, some new methods have been identified for the side chain cleavage of prednisolone (1) to form 11--hydroxy-1,4-androstadiene-3,17-dione (11--hydroxy ADD). Prednisolone upon reaction with zinc chloride in dry THF results in the formation of cleavage product in good yield (76%). 11--hydroxy ADD (2) has been formed in moderate yield (60%) under the Reformatsky reaction conditions by reacting with zincate. While performing the Wittig reaction using stable ylides, again results in the formation of compound 2 in good yield (56%). Side chain cleavage of prednisolone was confirmed from the physical and analytical data and similar when compared with the literature reports.

  5. [History of corticotherapy].

    Science.gov (United States)

    Chast, F

    2013-05-01

    Corticosteroids emerged in the late 1940s, at a time when steroid chemistry began to offer new therapeutic approaches. Extractive chemistry (T. Reichstein), chemical synthesis (E.C. Kendall) and clinical investigations (P. Hench) were combined to result in the discovery of cortisone in 1948, leading to a long series of related derivatives. Besides their first applications to treat Addison's disease and rheumatic or inflammatory diseases, corticosteroids could easily correct many metabolic and functional symptoms. Fluoridation of the steroid skeleton allowed the development of more active and better tolerated molecules. Corticosteroids have revolutionized the treatment of allergic diseases or immunity troubles, graft rejection, many dermatological, respiratory, digestive, eye diseases, etc. It is used today in all areas of therapeutic.

  6. Three-dimensional solubility parameters and their use in characterising the permeation of drugs through the skin.

    Science.gov (United States)

    Groning, R; Braun, F J

    1996-05-01

    The physico-chemical properties of drug substances are major determinants of their transdermal absorption. In the present study the concept of the three-dimensional solubility parameters of Hansen was applied in conjunction with the Bagley projection to describe the permeation of drugs and model substances through the skin. Drug permeation data from the literature were compared with the calculated solubility parameters of the drugs. It was demonstrated that the permeation of drugs can be estimated by their position in the Bagley diagram. There is a linear correlation between the logarithm of the skin permeation of drugs and the exchange cohesive energy for the steroids testosterone, progesterone, hydrocortisone acetate, corticosterone, cortisone, and dexamethasone. A linear correlation can be confirmed for the permeation of glyceryl trinitrate, digitoxin, oestradiol, scopolamine, atropine, diethylcarbamazine, fentanyl, and chlorpheniramine. In the case of morphine, codeine, sufentanil, meperidine and hydromorphone there is a linear relationship, too.

  7. [Sarcoidosis - diagnosis and therapy today].

    Science.gov (United States)

    Christ, R

    1980-12-15

    The etiology of sarcoidosis is still unclear. It belongs to the most frequent lung diseases; but also nearly all other tissues and organs may be established. One third of the diseases runs under the picture of the acute form of the course (Loefgren's syndrome). A histologic ascertainment is to be striven for. The tendency to spontaneous remission is great. This is still additionally supported by the application of cortison derivatives. In the individual case the indication to medicamentous therapy results from the tendency of the course of the disease, from the degree of the affection of organs and the clinico-functional disturbance. In 80 patients with Loefgren's syndrome the author adopts a definite attitude to diagnostics and therapy.

  8. [Morphological characteristics of the destructive and reparative changes in tuberculosis in those dying of nontubercular diseases].

    Science.gov (United States)

    Zagurov, G

    1975-01-01

    The evolution of destructive and restorative alterations was morphologically followed up in 82 tuberculotics that died of non-tiberculous diseases. In the majority of the deceased, the restorative alterations were observed with manifested mesenchymal and immunologic reactions with morphological peculiarities as in the treated with anti tuberculous remedies. The destructive alteration are clearly manifested and the restorative manifestations are depressed in tuberculotics with non-treated diabetes and osteomyelitis treated with cortison. In a negligible part of the patients died of non-tuberculous diseases, a reactivation of the foci developed around the fibrocaseous lung foci, tracheobronchial lymph nodes, kidneys and suprarenals, manifested with filamented neutrophyils in the calcified and caseous matter, fresh necrosis, tubercula, specific granular tissue, friable capsule with appearance of lymphoid cells and specific granular tissue.

  9. A case of androgen-secreting adrenal carcinoma with non-classical congenital adrenal hyperplasia

    Directory of Open Access Journals (Sweden)

    Tarun Varma

    2013-01-01

    Full Text Available Androgen excess is one of the most common and disturbing endocrine disorder of reproductive-aged women, affecting approximately 7% of this population Androgen excess results in the development of androgenic features in the women affected, with the development of hirsutism, androgenic alopecia, ovulatory dysfunction, and, if extreme, even virilization and masculinization. Adrenocortical carcinoma (ACC is a rare malignancy accounting for 0.02% of all annual cancers reported. About 60% are functional tumors secreting hormones, with its consequent clinical manifestations, the Cushing′s syndrome due to cortisone, virilization due to androgens, feminization due to estrogens, or hypertension due to aldosterone. Adrenal tumors that secrete androgens exclusively are extremely rare. Here, we present a rare case of androgen-secreting adrenocortical carcinoma with non-classical congenital adrenal hyperplasia.

  10. [Leber's hereditary optic neuropathy].

    Science.gov (United States)

    Leo-Kottler, B; Wissinger, B

    2011-12-01

    Leber's hereditary optic neuropathy (LHON) is a rare disease primarily affecting the retinal ganglion cells. In most cases patients with LHON develop permanent visual loss with a large central scotoma in the visual field of both eyes. The optic disc becomes partially or completely pale. At the onset of the disease many patients are considered to suffer from an optic neuritis and are treated under the diagnostic and therapeutic regimen of optic neuritis. LHON is mostly only considered when high dose cortisone therapy fails to be effective or the second eye is affected. Thereafter, molecular genetic analysis will prove LHON in these cases. Detailed anamnesis including pedigree analysis in combination with observance of the peripapillary microangiopathic alterations at the fundus will help to speed up the diagnosis of LHON, but even after exact clinical and molecular genetic diagnosis of LHON some aspects of the disease still remain a mystery today.

  11. [Reduction of obesity-related metabolic risk by modulating tissue exposition to cortisol].

    Science.gov (United States)

    Iovino, Alessandra; Paquot, Nicolas; Scheen, André J

    2010-09-01

    The 11-beta-hydroxysteroid dehydrogenase type 1 (11HSD1) enzyme promotes the local conversion from cortisone to cortisol, especially in the liver and the adipose tissue. It may play a role in the pathophysiology of abdominal obesity and the metabolic syndrome, both showing some similarities with the Cushing syndrome. Considering experimental results obtained in rodents, the inhibition of this enzyme could exert favourable metabolic effects, with significant reductions in plasma glucose, insulin resistance and dyslipidaemia. Synthetic inhibitors of 11HSD1 are currently in development with encouraging preliminary results, first in animals, and more recently in humans. Selective inhibitors of 11HSD1 may represent an innovative approach in the pharmacological management of obesity, metabolic syndrome and type 2 diabetes in a near future.

  12. Management considerations for the adult with congenital adrenal hyperplasia.

    Science.gov (United States)

    Auchus, Richard J

    2015-06-15

    The congenital adrenal hyperplasias (CAH) are a group of genetic defects in cortisol biosynthesis, most commonly steroid 21-hydroxylase deficiency (21OHD). With the advent of cortisone therapy in the 1960s and newborn screening in the 1990s, most children with 21OHD now reach adulthood. The needs and concerns of adults with 21OHD overlap with those of children, but the focus and approach shift as these patients reach adulthood. Cohort studies suggest that adults with 21OHD experience significant health concerns such as infertility, obesity, short stature, neoplasia, and bone loss, as well as reduced quality of life. Nevertheless, the spectrum of health status and disease severity is broad, but only some of the reasons for these disparities are known. This review will summarize the current state of knowledge and suggested approaches to management adults with classic 21OHD, plus a few major considerations for adults with nonclassic 21OHD.

  13. Discovery of adamantyl heterocyclic ketones as potent 11β-hydroxysteroid dehydrogenase type 1 inhibitors.

    Science.gov (United States)

    Su, Xiangdong; Vicker, Nigel; Thomas, Mark P; Pradaux-Caggiano, Fabienne; Halem, Heather; Culler, Michael D; Potter, Barry V L

    2011-08-01

    11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) plays a key role in converting intracellular cortisone to physiologically active cortisol, which is implicated in the development of several phenotypes of metabolic syndrome. Inhibition of 11β-HSD1 activity with selective inhibitors has beneficial effects on various conditions, including diabetes, dyslipidemia and obesity, and therefore constitutes a promising strategy to discover novel therapies for metabolic and cardiovascular diseases. A series of novel adamantyl heterocyclic ketones provides potent and selective inhibitors of human 11β-HSD1. Lead compounds display low nanomolar inhibition against human and mouse 11β-HSD1 and are selective with no activity against 11β-HSD2 and 17β-HSD1. Selected potent 11β-HSD1 inhibitors show moderate metabolic stability upon incubation with human liver microsomes and weak inhibition of human CYP450 enzymes.

  14. Discovery of Adamantyl Heterocyclic Ketones as Potent 11β-Hydroxysteroid Dehydrogenase Type 1 Inhibitors

    Science.gov (United States)

    Su, Xiangdong; Vicker, Nigel; Thomas, Mark P; Pradaux-Caggiano, Fabienne; Halem, Heather; Culler, Michael D; Potter, Barry V L

    2011-01-01

    11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) plays a key role in converting intracellular cortisone to physiologically active cortisol, which is implicated in the development of several phenotypes of metabolic syndrome. Inhibition of 11β-HSD1 activity with selective inhibitors has beneficial effects on various conditions, including diabetes, dyslipidemia and obesity, and therefore constitutes a promising strategy to discover novel therapies for metabolic and cardiovascular diseases. A series of novel adamantyl heterocyclic ketones provides potent and selective inhibitors of human 11β-HSD1. Lead compounds display low nanomolar inhibition against human and mouse 11β-HSD1 and are selective with no activity against 11β-HSD2 and 17β-HSD1. Selected potent 11β-HSD1 inhibitors show moderate metabolic stability upon incubation with human liver microsomes and weak inhibition of human CYP450 enzymes. PMID:21608132

  15. Management of Labral and Chondral Disease in Hip Preservation Surgery.

    Science.gov (United States)

    Salata, Michael J; Vasileff, William K

    2015-12-01

    The techniques utilized for the management of articular cartilage and labrum injuries during hip preservation surgery have changed dramatically recently. Conservative treatment may involve image-guided injection of cortisone or viscosupplementation in conjunction with oral NSAIDs and physical therapy. Damage to the labrum runs a broad spectrum, and the treatments are individualized, but span from debridement to repair and reconstruction. The overarching goal of labral treatment is to restore the native functions of the labrum to allow for more normal biomechanical function. Similarly, cartilage injuries can be managed a number of different ways, including with debridement, microfracture or drilling, cartilage transplants, and higher level restorative techniques. These cartilage restoration techniques have evolved rapidly as well, and may include the use of scaffolds, allograft cartilage cells, and other stem-cell-related procedures.

  16. Study of Relaxation by Traditional Medicinal Methods on Biological Indexes of the Elderly (Abstract)

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The objective of the study was to prove the relaxation effect of traditional medicine by objective biological indexes by modern scientific methods.  Fifty healthy elderly people, aged from 60 to 75, were selected to have traditional medicinal relaxing practice, that is, to relax their body in 3 directions: two sides, in front and backward, and breath naturally, 30 minutes a day, 8 weeks as a cycle. (1) The changes of electroencephalogram (EEG), rheoencephalogram (REG) were measured before and after the treatment cycle. Breath frequency and SaO2 contents were measured before and after the treatment cycle by Pulse oxymeter. (2) As for the circulatory system, pulse frequency, blood pressure, blood influx of limbs were measured before and after the treatment cycle. (3) Biochemical indexes (including index of cholesterol, triglyceride, blood sugar, cortisone, catecholamine) were measured before and after the treatment cycle.……

  17. Study of Relaxation by Traditional Medicinal Methods on Biological Indexes of the Elderly (Abstract)

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    @@The objective of the study was to prove the relaxation effect of traditional medicine by objective biological indexes by modern scientific methods. Fifty healthy elderly people, aged from 60 to 75, were selected to have traditional medicinal relaxing practice, that is, to relax their body in 3 directions: two sides, in front and backward, and breath naturally, 30 minutes a day, 8 weeks as a cycle. (1) The changes of electroencephalogram (EEG), rheoencephalogram (REG) were measured before and after the treatment cycle. Breath frequency and SaO2 contents were measured before and after the treatment cycle by Pulse oxymeter. (2) As for the circulatory system, pulse frequency, blood pressure, blood influx of limbs were measured before and after the treatment cycle. (3) Biochemical indexes (including index of cholesterol, triglyceride, blood sugar, cortisone, catecholamine) were measured before and after the treatment cycle.

  18. Data related to inflammation and cholesterol deposition triggered by macrophages exposition to modified LDL.

    Science.gov (United States)

    Toledo, Juan; Esteve, Montserrat; Grasa, Mar; Ledda, Angelo; Garda, Horacio; Gulfo, José; Ludovico, Ivo Díaz; Ramella, Nahuel; Gonzalez, Marina

    2016-09-01

    This article supports experimental evidence on the time-dependent effect on gene expression related to inflammation and cholesterol deposition in lipid-loaded cells. The cells employed were human monocytes THP1 line transformed into macrophages by treatment with phorbol esters. Macrophages were treated at different times with oxidized low density lipoprotein (Ox-LDL) and then gene expression was measured. We also include data about the different types of oxidized lipoprotein obtained (low, media or high oxidation) for differential exposure with Cu ions. These data include characterization to lipid and protein peroxidative damage and also quantification of cell viability by exposure to native and modified LDL. The present article complements data published in "Decreased OxLDL uptake and cholesterol efflux in THP1 cells elicited by cortisol and by cortisone through 11β-hydroxysteroid dehydrogenase type 1" Ledda et al. (in press) [1].

  19. Diet-induced weight loss has chronic tissue-specific effects on glucocorticoid metabolism in overweight postmenopausal women.

    Science.gov (United States)

    Stomby, A; Simonyte, K; Mellberg, C; Ryberg, M; Stimson, R H; Larsson, C; Lindahl, B; Andrew, R; Walker, B R; Olsson, T

    2015-05-01

    Tissue-specific glucocorticoid metabolism is altered in obesity, and may increase cardiovascular risk. This dysregulation is normalized by short-term calorie restriction and weight loss, an effect that varies with dietary macronutrient composition. However, tissue-specific glucocorticoid metabolism has not been studied during long-term (>6 months) dietary interventions. Therefore our aim was to test whether long-term dietary interventions, either a paleolithic-type diet (PD) or a diet according to Nordic nutrition recommendations (NNR) could normalize tissue-specific glucocorticoid metabolism in overweight and obese women. Forty-nine overweight/obese postmenopausal women were randomized to a paleolithic diet or a diet according to NNR for 24 months. At baseline, 6 and 24 months anthropometric measurements, insulin sensitivity, excretion of urinary glucocorticoid metabolites in 24-hour collections, conversion of orally administered cortisone to plasma cortisol and transcript levels of 11β hydroxysteroid dehydrogenase type 1 (11βHSD1) in subcutaneous adipose tissue were studied. Both diet groups achieved significant and sustained weight loss. Weight loss with the PD was greater than on NNR diet after 6 months (Pdiet groups (P=0.036). Consistent with increased liver 11βHSD1, conversion of oral cortisone to cortisol increased at 6 months (P=0.023) but was unchanged compared with baseline by 24 months. Long-term weight loss in postmenopausal women has tissue-specific and time-dependent effects on glucocorticoid metabolism. This may alter local-tissue cortisol exposure contributing to improved metabolic function during weight loss.

  20. Zebrafish 20β-hydroxysteroid dehydrogenase type 2 is important for glucocorticoid catabolism in stress response.

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    Janina Tokarz

    Full Text Available Stress, the physiological reaction to a stressor, is initiated in teleost fish by hormone cascades along the hypothalamus-pituitary-interrenal (HPI axis. Cortisol is the major stress hormone and contributes to the appropriate stress response by regulating gene expression after binding to the glucocorticoid receptor. Cortisol is inactivated when 11β-hydroxysteroid dehydrogenase (HSD type 2 catalyzes its oxidation to cortisone. In zebrafish, Danio rerio, cortisone can be further reduced to 20β-hydroxycortisone. This reaction is catalyzed by 20β-HSD type 2, recently discovered by us. Here, we substantiate the hypothesis that 20β-HSD type 2 is involved in cortisol catabolism and stress response. We found that hsd11b2 and hsd20b2 transcripts were up-regulated upon cortisol treatment. Moreover, a cortisol-independent, short-term physical stressor led to the up-regulation of hsd11b2 and hsd20b2 along with several HPI axis genes. The morpholino-induced knock down of hsd20b2 in zebrafish embryos revealed no developmental phenotype under normal culture conditions, but prominent effects were observed after a cortisol challenge. Reporter gene experiments demonstrated that 20β-hydroxycortisone was not a physiological ligand for the zebrafish glucocorticoid or mineralocorticoid receptor but was excreted into the fish holding water. Our experiments show that 20β-HSD type 2, together with 11β-HSD type 2, represents a short pathway in zebrafish to rapidly inactivate and excrete cortisol. Therefore, 20β-HSD type 2 is an important enzyme in stress response.

  1. Pharmacogenetics of glucocorticoid replacement could optimize the treatment of congenital adrenal hyperplasia due to 21-hydroxylase deficiency

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    Ricardo P. P. Moreira

    2011-01-01

    Full Text Available INTRODUCTION: 21-hydroxylase deficiency is an autosomal recessive disorder that causes glucocorticoid deficiency and increased androgen production. Treatment is based on glucocorticoid replacement; however, interindividual variability in the glucocorticoid dose required to achieve adequate hormonal control has been observed. OBJECTIVE: The present study aimed to evaluate the association between polymorphic variants involved inglucocorticoid action and/or metabolism and the mean daily glucocorticoid dose in 21-hydroxylase deficiency patients. METHODS: We evaluated 53 patients with classical forms of 21-hydroxylase deficiency who were receiving cortisone acetate. All patients were between four and six years of age and had normal androgen levels. RESULTS: The P450 oxidoreductase A503V, HSD11B1 rs12086634, and CYP3A7*1C variants were found in 19%, 11.3% and 3.8% of the patients, respectively. The mean ± SD glucocorticoid dose in patients with the CYP3A7*1C and wild-type alleles was 13.9 ± 0.8 and 19.5 ± 3.2 mg/m²/d, respectively. We did not identify an association between the P450 oxidoreductase or HSD11B1 allelic variants and the mean glucocorticoid dose. CONCLUSION: Patients carrying the CYP3A7*1C variant required a significantly lower mean glucocorticoid dose. Indeed, the CYP3A7*1C allele accounted for 20% of the variability in the cortisone acetate dose. The analysis of genes involved in glucocorticoid metabolism may be useful in the optimization of treatment of 21-hydroxylase deficiency.

  2. Suppression of the Nrf2-dependent antioxidant response by glucocorticoids and 11β-HSD1-mediated glucocorticoid activation in hepatic cells.

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    Denise V Kratschmar

    Full Text Available BACKGROUND: Nuclear factor (erythroid-derived 2-like 2 (Nrf2 is a key transcription factor regulating a plethora of detoxifying enzymes and antioxidant genes involved in drug metabolism and defence against oxidative stress. The glucocorticoid receptor (GR is a ligand-induced transcription factor involved in the regulation of energy supply for metabolic needs to cope with various stressors. GR activity is controlled by glucocorticoids, which are synthesized in the adrenal glands and regenerated mainly in the liver from inactive cortisone by 11β-hydroxysteroid dehydrogenase-1 (11β-HSD1. METHODS AND PRINCIPAL FINDINGS: Using transfected HEK-293 cells and hepatic H4IIE cells we show that glucocorticoids, activated by 11β-HSD1 and acting through GR, suppress the Nrf2-dependent antioxidant response. The expression of the marker genes NQO1, HMOX1 and GST2A was suppressed upon treatment of 11β-HSD1 expressing cells with cortisone, an effect that was reversed by 11β-HSD1 inhibitors. Furthermore, our results demonstrate that elevated glucocorticoids lowered the ability of cells to detoxify H(2O(2. Moreover, a comparison of gene expression in male and female rats revealed an opposite sexual dimorphism with an inverse relationship between 11β-HSD1 and Nrf2 target gene expression. CONCLUSIONS: The results demonstrate a suppression of the cellular antioxidant defence capacity by glucocorticoids and suggest that elevated 11β-HSD1 activity may lead to impaired Nrf2-dependent antioxidant response. The gender-specific differences in hepatic expression levels of 11β-HSD1 and Nrf2 target genes and the impact of pharmacological inhibition of 11β-HSD1 on improving cellular capacity to cope with oxidative stress warrants further studies in vivo.

  3. Risk of classical Kaposi sarcoma by plasma levels of Epstein-Barr virus antibodies, sCD26, sCD23 and sCD30

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    Viviano Enza

    2010-10-01

    Full Text Available Abstract Background To clarify the immunological alterations leading to classical Kaposi sarcoma (cKS among people infected with KS-associated herpesvirus (KSHV. Methods In a population-based study of 119 cKS cases, 105 KSHV-seropositive controls, and 155 KSHV-seronegative controls, we quantified plasma soluble cluster of differentiation (sCD levels and antibodies against Epstein-Barr virus nuclear antigen-1 (anti-EBNA-1 and viral capsid antigen (anti-VCA. Differences between groups in prevalence of low-tertile anti-EBNA-1 and high-tertile anti-VCA were compared by logistic regression. Continuous levels between groups and by presence of cKS co-factors among controls were compared by linear regression and Mann-Whitney-Wilcoxon methods. Results Comparisons of cKS cases to seropositive controls and of seropositive to seronegative controls revealed no significant differences. However, controls with known cKS cofactors (male sex, nonsmoking, diabetes and cortisone use had significantly lower levels of anti-EBNA (P = 0.0001 - 0.07 and anti-VCA (P = 0.0001 - 0.03. Levels of sCD26 were significantly lower for male and non-smoking controls (Padj ≤ 0.03, and they were marginally lower with older age and cortisone use (Padj ≤ 0.09. Conclusions Anti-EBV and sCD26 levels were associated with cofactors for cKS, but they did not differ between cKS cases and matched controls. Novel approaches and broader panels of assays are needed to investigate immunological contributions to cKS.

  4. Mineralocorticoid replacement during infancy for salt wasting congenital adrenal hyperplasia due to 21-hydroxylase deficiency

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    Larissa G. Gomes

    2013-01-01

    Full Text Available OBJECTIVE: The protocols for glucocorticoid replacement in children with salt wasting 21-hydroxylase deficiency are well established; however, the current recommendation for mineralocorticoid replacement is general and suggests individualized dose adjustments. This study aims to retrospectively review the 9-∝-fludrocortisone dose regimen in salt wasting 21-hydroxylase deficient children who have been adequately treated during infancy. METHODS: Twenty-three salt wasting 21-hydroxylase deficient patients with good anthropometric and hormonal control were followed in our center since diagnosis. The assessments of cortisone acetate and 9-∝-fludrocortisone doses, anthropometric parameters, and biochemical and hormonal levels were rigorously evaluated in pre-determined intervals from diagnosis to two years of age. RESULTS: The 9-∝-fludrocortisone doses decreased over time during the first and second years of life; the median fludrocortisone doses were 200 µg at 0-6 months, 150 µg at 7-18 months and 125 µg at 19-24 months. The cortisone acetate dose per square meter was stable during follow-up (median = 16.8 mg/m²/day. The serum sodium, potassium and plasma rennin activity levels during treatment were normal, except in the first month of life, when periodic 9-∝-fludrocortisone dose adjustments were made. CONCLUSIONS: The mineralocorticoid needs of salt wasting 21-hydroxylase deficient patients are greater during early infancy and progressively decrease during the first two years of life, which confirms that a partial aldosterone resistance exists during this time. Our study proposes a safety regiment for mineralocorticoid replacement during this critical developmental period.

  5. Down-regulation of 11β-hydroxysteroid dehydrogenase type 2 by bortezomib sensitizes Jurkat leukemia T cells against glucocorticoid-induced apoptosis.

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    Yi Tao

    Full Text Available 11β-Hydroxysteroid dehydrogenases type 2 (11β-HSD2, a key regulator for pre-receptor metabolism of glucocorticoids (GCs by converting active GC, cortisol, to inactive cortisone, has been shown to be present in a variety of tumors. But its expression and roles have rarely been discussed in hematological malignancies. Proteasome inhibitor bortezomib has been shown to not only possess antitumor effects but also potentiate the activity of other chemotherapeutics. In this study, we demonstrated that 11β-HSD2 was highly expressed in two GC-resistant T-cell leukemic cell lines Jurkat and Molt4. In contrast, no 11β-HSD2 expression was found in two GC-sensitive non-hodgkin lymphoma cell lines Daudi and Raji as well as normal peripheral blood T cells. Inhibition of 11β-HSD2 by 11β-HSD inhibitor 18β-glycyrrhetinic acid or 11β-HSD2 shRNA significantly increased cortisol-induced apoptosis in Jurkat cells. Additionally, pretreatment of Jurkat cells with low-dose bortezomib resulted in increased cellular sensitivity to GC as shown by elevated induction of apoptosis, more cells arrested at G1 stage and up-regulation of GC-induced leucine zipper which is an important mediator of GC action. Furthermore, we clarified that bortezomib could dose-dependently inhibit 11β-HSD2 messenger RNA and protein levels as well as activity (cortisol-cortisone conversion through p38 mitogen-activated protein kinase signaling pathway. Therefore, we suggest 11β-HSD2 is, at least partially if not all, responsible for impaired GC suppression in Jurkat cells and also indicate a novel mechanism by which proteasome inhibitor bortezomib may influence GC action.

  6. Crystal Structure of Human Liver delta {4}-3-Ketosteroid 5 beta-Reductase (AKR1D1) and Implications for Substrate Binding and Catalysis

    Energy Technology Data Exchange (ETDEWEB)

    Di Costanzo,L.; Drury, J.; Penning, T.; Christianson, D.

    2008-01-01

    AKR1D1 (steroid 5{beta}-reductase) reduces all 4-3-ketosteroids to form 5{beta}-dihydrosteroids, a first step in the clearance of steroid hormones and an essential step in the synthesis of all bile acids. The reduction of the carbon-carbon double bond in an a,{beta}-unsaturated ketone by 5{beta}-reductase is a unique reaction in steroid enzymology because hydride transfer from NADPH to the {beta}-face of a 4-3-ketosteroid yields a cis-A/B-ring configuration with an {approx}90 bend in steroid structure. Here, we report the first x-ray crystal structure of a mammalian steroid hormone carbon-carbon double bond reductase, human 4-3-ketosteroid 5{beta}-reductase (AKR1D1), and its complexes with intact substrates. We have determined the structures of AKR1D1 complexes with NADP+ at 1.79- and 1.35- Angstroms resolution (HEPES bound in the active site), NADP+ and cortisone at 1.90- Angstroms resolution, NADP+ and progesterone at 2.03- Angstroms resolution, and NADP+ and testosterone at 1.62- Angstroms resolution. Complexes with cortisone and progesterone reveal productive substrate binding orientations based on the proximity of each steroid carbon-carbon double bond to the re-face of the nicotinamide ring of NADP+. This orientation would permit 4-pro-(R)-hydride transfer from NADPH. Each steroid carbonyl accepts hydrogen bonds from catalytic residues Tyr58 and Glu120. The Y58F and E120A mutants are devoid of activity, supporting a role for this dyad in the catalytic mechanism. Intriguingly, testosterone binds nonproductively, thereby rationalizing the substrate inhibition observed with this particular steroid. The locations of disease-linked mutations thought to be responsible for bile acid deficiency are also revealed.

  7. Intense physical exercise increases systemic 11beta-hydroxysteroid dehydrogenase type 1 activity in healthy adult subjects.

    Science.gov (United States)

    Dovio, Andrea; Roveda, Eliana; Sciolla, Chiara; Montaruli, Angela; Raffaelli, Andrea; Saba, Alessandro; Calogiuri, Giovanna; De Francia, Silvia; Borrione, Paolo; Salvadori, Piero; Carandente, Franca; Angeli, Alberto

    2010-03-01

    Intense physical exercise activates the hypothalamic-pituitary-adrenocortical axis but little is known about changes in glucocorticoid sensitivity at the target cell level. No data are available on the acute effects of exercise on 11beta-hydroxysteroid dehydrogenase (11beta-HSD) type 1 activity, which generates biologically active cortisol from inactive cortisone and is expressed also in skeletal muscle. Fifteen healthy, trained males (age mean +/- SE 28 +/- 1) were assessed on three non-consecutive days: at rest, during an endurance and strength sessions. During each session, between 1000 and 1600 hours, 6-h urine and four salivary samples were collected. Urinary total tetrahydrocortisol (THF) + alloTHF, tetrahydrocortisone (THE), cortisol (F) and cortisone (E) were measured with HPLC-tandem mass spectrometry; urinary-unconjugated F and E were measured by HPLC-UV. Salivary cortisol and interleukin (IL)-6 were measured by RIA and ELISA, respectively. Both endurance and strength exercises caused an increase in (THF + alloTHF)/THE ratio (mean +/- SE 1.90 +/- 0.07 and 1.82 +/- 0.05 vs. 1.63 +/- 0.06, P < 0.01 and P = 0.03, respectively), consistent with increased systemic 11beta-HSD type 1 activity. No relationship was found with age, BMI, VO(2max) maximal power load or perceived exertion. No significant change was apparent in F/E ratio, an index of 11beta-HSD type 2 activity. No effect of exercise on salivary cortisol and IL-6 was observed, whereas a significant effect of sampling time was found. Intense physical exercise acutely increases systemic 11beta-HSD type 1 activity in humans. Such an increase may lead to higher cortisol concentration in target tissues, notably in skeletal muscle where it could contribute to limit exercise-induced muscle inflammatory response.

  8. Risk factors and predictors of carbapenem-resistant Pseudomonas aeruginosa and Acinetobacter baumannii mortality in critically ill bacteraemic patients over a 6-year period (2010-15): antibiotics do matter.

    Science.gov (United States)

    Papadimitriou-Olivgeris, Matthaios; Fligou, Fotini; Spiliopoulou, Anastasia; Koutsileou, Kyriaki; Kolonitsiou, Fevronia; Spyropoulou, Aikaterini; Zotou, Anastasia; Marangos, Markos; Anastassiou, Evangelos D; Christofidou, Myrto; Spiliopoulou, Iris

    2017-07-31

    Acinetobacter baumannii and Pseudomonas aeruginosa provoke serious infections, especially in intensive care unit (ICU) patients. The risk factors and predictors of mortality for P. aeruginosa (n=84; 46 carbapenem-resistant) and A. baumannii (n=129; all carbapenem-resistant) bloodstream infections (BSIs) in an ICU were evaluated. Antibiotic susceptibility testing was performed using the agar disk diffusion method according to EUCAST guidelines. The minimum inhibitory concentration was determined by a gradient method (Etest). Multilocus sequence typing (MLST) was performed for P. aeruginosa during the carbapenem-resistant outbreak in 2014. Epidemiological data were collected from the patients' chart reviews.Results/Key findings. Hospitalization during the summer months, prior KPC-producing Klebsiella pneumoniae (KPC-Kp) BSI, and the administration of tigecycline, aminoglycosides and cortisone were independently associated with P. aeruginosa BSIs. MLST revealed the dissemination of clone ST227, including carbapenem-resistant P. aeruginosa strains. Hospitalization during the summer months, prior KPC-Kp BSI, and the administration of antibiotics, carbapenem and cortisone were independently associated with A. baumannii BSIs. The 30-day mortality rate for P. aeruginosa and A. baumannii BSI was 45.2 and 39.5 %, respectively. Sequential organ failure assessment (SOFA) score at onset, septic shock, age, and prior KPC-Kp BSI were significantly associated with P. aeruginosa BSI mortality. The administration of at least one active antibiotic was identified as a predictor of a good prognosis. Septic shock and simplified acute physiology score (SAPS) II at onset were independently associated with A. baumannii BSI mortality. The administration of at least one active antibiotic and colistin-vancomycin co-administration were identified as predictors of a good prognosis. KPC-Kp infection predisposes ICU patients to BSI by either A. baumannii or P. aeruginosa. The administration of

  9. Non-Invasive Measurement of Adrenocortical Activity in Blue-Fronted Parrots (Amazona aestiva, Linnaeus, 1758.

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    João C P Ferreira

    Full Text Available Parrots kept in zoos and private households often develop psychological and behavioural disorders. Despite knowing that such disorders have a multifactorial aetiology and that chronic stress is involved, little is known about their development mainly due to a poor understanding of the parrots' physiology and the lack of validated methods to measure stress in these species. In birds, blood corticosterone concentrations provide information about adrenocortical activity. However, blood sampling techniques are difficult, highly invasive and inappropriate to investigate stressful situations and welfare conditions. Thus, a non-invasive method to measure steroid hormones is critically needed. Aiming to perform a physiological validation of a cortisone enzyme immunoassay (EIA to measure glucocorticoid metabolites (GCM in droppings of 24 Blue-fronted parrots (Amazona aestiva, two experiments were designed. During the experiments all droppings were collected at 3-h intervals. Initially, birds were sampled for 24 h (experiment 1 and one week later assigned to four different treatments (experiment 2: Control (undisturbed, Saline (0.2 mL of 0.9% NaCl IM, Dexamethasone (1 mg/kg IM and Adrenocorticotropic hormone (ACTH; 25 IU IM. Treatments (always one week apart were applied to all animals in a cross-over study design. A daily rhythm pattern in GCM excretion was detected but there were no sex differences (first experiment. Saline and dexamethasone treatments had no effect on GCM (not different from control concentrations. Following ACTH injection, GCM concentration increased about 13.1-fold (median at the peak (after 3-9 h, and then dropped to pre-treatment concentrations. By a successful physiological validation, we demonstrated the suitability of the cortisone EIA to non-invasively monitor increased adrenocortical activity, and thus, stress in the Blue-fronted parrot. This method opens up new perspectives for investigating the connection between behavioural

  10. Glucocorticoid Regulation of Food-Choice Behavior in Humans: Evidence from Cushing's Syndrome.

    Science.gov (United States)

    Moeller, Scott J; Couto, Lizette; Cohen, Vanessa; Lalazar, Yelena; Makotkine, Iouri; Williams, Nia; Yehuda, Rachel; Goldstein, Rita Z; Geer, Eliza B

    2016-01-01

    The mechanisms by which glucocorticoids regulate food intake and resulting body mass in humans are not well-understood. One potential mechanism could involve modulation of reward processing, but human stress models examining effects of glucocorticoids on behavior contain important confounds. Here, we studied individuals with Cushing's syndrome, a rare endocrine disorder characterized by chronic excess endogenous glucocorticoids. Twenty-three patients with Cushing's syndrome (13 with active disease; 10 with disease in remission) and 15 controls with a comparably high body mass index (BMI) completed two simulated food-choice tasks (one with "explicit" task contingencies and one with "probabilistic" task contingencies), during which they indicated their objective preference for viewing high calorie food images vs. standardized pleasant, unpleasant, and neutral images. All participants also completed measures of food craving, and approximately half of the participants provided 24-h urine samples for assessment of cortisol and cortisone concentrations. Results showed that on the explicit task (but not the probabilistic task), participants with active Cushing's syndrome made fewer food-related choices than participants with Cushing's syndrome in remission, who in turn made fewer food-related choices than overweight controls. Corroborating this group effect, higher urine cortisone was negatively correlated with food-related choice in the subsample of all participants for whom these data were available. On the probabilistic task, despite a lack of group differences, higher food-related choice correlated with higher state and trait food craving in active Cushing's patients. Taken together, relative to overweight controls, Cushing's patients, particularly those with active disease, displayed a reduced vigor of responding for food rewards that was presumably attributable to glucocorticoid abnormalities. Beyond Cushing's, these results may have relevance for elucidating

  11. Association between umbilical cord glucocorticoids and blood pressure at age 3 years

    Directory of Open Access Journals (Sweden)

    Rich-Edwards Janet W

    2008-08-01

    Full Text Available Abstract Background Animal data show that decreased activity of placental 11-beta-hydroxysteroid dehydrogenase type 2 (11β-HSD2, which potently inactivates glucocorticoids (e.g. cortisol to inert forms (cortisone, allows increased access of maternal glucocorticoids to the fetus and 'programs' hypertension. Data in humans are limited. We examined in humans the association between venous umbilical cord blood glucocorticoids, a potential marker for placental 11β-HSD2 enzyme activity, and blood pressure at age 3 years. Methods Among 286 newborns in Project Viva, a prospective pre-birth cohort study based in eastern Massachusetts, we measured cortisol (F and cortisone (E in venous cord blood and used the ratio of F/E as a marker for placental 11β-HSD2 activity. We measured blood pressure (BP when the offspring reached age 3 years. Using mixed effects regression models to control for BP measurement conditions, maternal and child characteristics, we examined the association between the F/E ratio and child BP. Results At age 3 years, each unit increase in the F/E ratio was associated with a 1.6 mm Hg increase in systolic BP (95% CI 0.0 to 3.1. The F/E ratio was not associated with diastolic blood pressure or birth weight for gestational age z-score. Conclusion A higher F/E ratio in umbilical venous cord blood, likely reflecting reduced placental 11β-HSD2 activity, was associated with higher systolic blood pressure at age 3 years. Our data suggest that increased fetal exposure to active maternal glucocorticoids may program later systolic blood pressure.

  12. Hymenolepis nana: worm recovery from congenitally athymic nude and phenotypically normal rats and mice.

    Science.gov (United States)

    Ito, A; Kamiyama, T

    1984-10-01

    When eggs or mouse-derived cysticercoids of Hymenolepis nana were inoculated into previously uninfected congenitally athymic nude (rnu/rnu) rats of an outbred Rowett strain, they failed to mature in the intestinal lumen. They also failed to mature in phenotypically normal (rnu/+) littermates, except when these hosts were treated with cortisone acetate from the beginning of the lumen phase. The Rowett rat, either thymus-deficient or not, was susceptible to tissue cysticercoids but resistant to luminal adults. It is therefore considered to be an unnatural host, at least for mouse-derived H. nana. There was little or no difference in susceptibility to initial tissue cysticercoids between these nude rats and phenotypically normal ones. The normal rats became completely resistant to reinfection with eggs and no secondary cysticercoids developed in their intestinal tissue, whereas the nude rats showed unaltered susceptibility to secondary tissue cysticercoids. Thus, acquired resistance to egg challenge, assessed by the failure of tissue cysticercoid recovery, was thymus-dependent. However, innate resistance to both a primary egg dose, assessed by the low recovery rates of tissue cysticercoids, and to a primary cysticercoid dose, assessed by the failure of luminal adult recovery, were thymus-independent. The effect of cortisone acetate to initiate maturation of H. nana appeared to be unrelated to thymus function. In contrast, all mice, either thymus-deficient or not, were highly susceptible to both phases. The number of worms recovered was more than 10 times greater than that of cysticercoids established in the rat's intestinal tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

  13. Effects of peroxisome proliferator-activated receptor-alpha and -gamma agonists on 11beta-hydroxysteroid dehydrogenase type 1 in subcutaneous adipose tissue in men.

    Science.gov (United States)

    Wake, Deborah J; Stimson, Roland H; Tan, Garry D; Homer, Natalie Z M; Andrew, Ruth; Karpe, Fredrik; Walker, Brian R

    2007-05-01

    In animals, peroxisome proliferator-activated receptor-alpha (PPARalpha) and PPARgamma agonists down-regulate 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) mRNA and activity in liver and adipose tissue, respectively, and PPARgamma agonists reduce ACTH secretion from corticotrope cells. Our objective was to test whether PPAR agonists alter cortisol secretion and peripheral regeneration by 11beta-HSD1 in humans and whether reduced cortisol action contributes to metabolic effects of PPARgamma agonists. Three randomized placebo-controlled crossover studies were conducted at a clinical research facility. Healthy men and patients with type 2 diabetes participated. INTERVENTIONS, OUTCOME MEASURES, AND RESULTS: In nine healthy men, 7 d of PPARalpha agonist (fenofibrate) or PPARgamma agonist (rosiglitazone) had no effect on cortisol secretion, hepatic cortisol generation after oral cortisone administration, or tracer kinetics during 9,11,12,12-[(2)H](4)-cortisol infusion, although rosiglitazone marginally reduced cortisol generation in sc adipose tissue measured by in vivo microdialysis. In 12 healthy men, 4-5 wk of rosiglitazone increased insulin sensitivity during insulin infusion but did not change 11beta-HSD1 mRNA or activity in sc adipose tissue, and insulin sensitization was unaffected by glucocorticoid blockade with a combination of metyrapone and RU38486. In 12 men with type 2 diabetes 12 wk of rosiglitazone reduced arteriovenous cortisone extraction across abdominal sc adipose tissue and reduced 11beta-HSD1 mRNA in sc adipose tissue but increased plasma cortisol concentrations. Neither PPARalpha nor PPARgamma agonists down-regulate 11beta-HSD1 or cortisol secretion acutely in humans. The early insulin-sensitizing effect of rosiglitazone is not dependent on reducing intracellular glucocorticoid concentrations. Reduced adipose 11beta-HSD1 expression and increased plasma cortisol during longer therapy with rosiglitazone probably reflect indirect effects, e

  14. Increased Whole-Body and Sustained Liver Cortisol Regeneration by 11β-Hydroxysteroid Dehydrogenase Type 1 in Obese Men With Type 2 Diabetes Provides a Target for Enzyme Inhibition

    Science.gov (United States)

    Stimson, Roland H.; Andrew, Ruth; McAvoy, Norma C.; Tripathi, Dhiraj; Hayes, Peter C.; Walker, Brian R.

    2011-01-01

    OBJECTIVE The cortisol-regenerating enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) amplifies glucocorticoid levels in liver and adipose tissue. 11β-HSD1 inhibitors are being developed to treat type 2 diabetes. In obesity, 11β-HSD1 is increased in adipose tissue but decreased in liver. The benefits of pharmacological inhibition may be reduced if hepatic 11β-HSD1 is similarly decreased in obese patients with type 2 diabetes. To examine this, we quantified in vivo whole-body, splanchnic, and hepatic 11β-HSD1 activity in obese type 2 diabetic subjects. RESEARCH DESIGN AND METHODS Ten obese men with type 2 diabetes and seven normal-weight control subjects were infused with 9,11,12,12-[2H]4cortisol (40%) and cortisol (60%) at 1.74 mg/h. Adrenal cortisol secretion was suppressed with dexamethasone. Samples were obtained from the hepatic vein and an arterialized hand vein at steady state and after oral administration of cortisone (5 mg) to estimate whole-body and liver 11β-HSD1 activity using tracer dilution. RESULTS In obese type 2 diabetic subjects, the appearance rate of 9,12,12-[2H]3cortisol in arterialized blood was increased (35 ± 2 vs. 29 ± 1 nmol/min, P cortisol production was not reduced (29 ± 6 vs. 29 ± 6 nmol/min), and cortisol appearance in the hepatic vein after oral cortisone was unchanged. CONCLUSIONS Whole-body 11β-HSD1 activity is increased in obese men with type 2 diabetes, whereas liver 11β-HSD1 activity is sustained, unlike in euglycemic obesity. This supports the concept that inhibitors of 11β-HSD1 are likely to be most effective in obese type 2 diabetic subjects. PMID:21266326

  15. Tendinopathy in Sport

    Science.gov (United States)

    Ackermann, Paul W.; Renström, Per

    2012-01-01

    Context: Tendinopathy is increasing in prevalence and accounts for a substantial part of all sports injuries and occupational disorders. Despite the magnitude of the disorder, high-quality scientific data on etiology and available treatments have been limited. Evidence Acquisition: The authors conducted a MEDLINE search on tendinopathy, or “tendonitis” or “tendinosis” or “epicondylitis” or “jumpers knee” from 1980 to 2011. The emphasis was placed on updates on epidemiology, etiology, and recent patient-oriented Level 1 literature. Results: Repetitive exposure in combination with recently discovered intrinsic factors, such as genetic variants of matrix proteins, and metabolic disorders is a risk factor for the development of tendinopathy. Recent findings demonstrate that tendinosis is characterized by a fibrotic, failed healing response associated with pathological vessel and sensory nerve ingrowth. This aberrant sensory nerve sprouting may partly explain increased pain signaling and partly, by release of neuronal mediators, contribute to the fibrotic alterations observed in tendinopathy. The initial nonoperative treatment should involve eccentric exercise, which should be the cornerstone (basis) of treatment of tendinopathy. Eccentric training combined with extracorporeal shockwave treatment has in some reports shown higher success rates compared to any therapies alone. Injection therapies (cortisone, sclerosing agents, blood products including platelet-rich plasma) may have short-term effects but have no proven long-term treatment effects or meta-analyses to support them. For epicondylitis, cortisone injections have demonstrated poorer long-time results than conservative physiotherapy. Today surgery is less indicated because of successful conservative therapies. New minioperative procedures that, via the endoscope, remove pathologic tissue or abnormal neoinnervation demonstrate promising results but need confirmation by Level 1 studies. Conclusions

  16. Rosiglitazone decreases 11beta-hydroxysteroid dehydrogenase type 1 in subcutaneous adipose tissue.

    Science.gov (United States)

    Mai, Knut; Andres, Janin; Bobbert, Thomas; Maser-Gluth, Christiane; Möhlig, Matthias; Bähr, Volker; Pfeiffer, Andreas F H; Spranger, Joachim; Diederich, Sven

    2007-09-01

    The peroxisome proliferator-activated receptor-gamma (PPARgamma) agonist rosiglitazone increases insulin sensitivity, which, in animal models, is comparable to the effect of a reduction in 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) activity. We therefore investigated whether rosiglitazone-induced insulin sensitivity is associated with changes in 11beta-HSD1 activity in different tissues. An oral glucose tolerance test (OGTT) and a euglycaemic hyperinsulinaemic clamp were performed in seven male volunteers [age 59.3 +/- 3.0 years, body mass index (BMI) 29.3 +/- 4.1 kg/m(2)] with impaired glucose tolerance before and after 8 weeks of rosiglitazone treatment. To assess hepatic 11beta-HSD1 activity, serum cortisol levels were measured after oral administration of cortisone acetate. 11beta-HSD1 activity and mRNA expression were assessed in abdominal subcutaneous fat biopsies. Total-body 11beta-HSD activities were estimated by calculating the urinary ratios of glucocorticoid metabolites. As expected, rosiglitazone improved insulin resistance and postprandial hyperglycaemia. In parallel, 11beta-HSD1 mRNA expression [100 +/- 0% (reference) vs. 68.5 +/- 9.3%, P < 0.01] and activity [0.18 +/- 0.02 vs. 0.13 +/- 0.02 pmol/min/mg, P < 0.05] decreased in abdominal subcutaneous fat, while an increase in hepatic 11beta-HSD1 activity was detected [the area under the curve (AUC) for the cortisol/cortisone ratio was 1319 +/- 76 vs. 955 +/- 59; P < 0.05]. No changes in BMI, waist-to-hip ratio (WHR) and whole-body 11beta-HSD1 activity were found. Part of the beneficial effects of rosiglitazone may be mediated by a reduction in the 11beta-HSD1 mRNA expression and activity in subcutaneous abdominal fat.

  17. C/EBPβ Promotes Immunity to Oral Candidiasis through Regulation of β-Defensins.

    Science.gov (United States)

    Simpson-Abelson, Michelle R; Childs, Erin E; Ferreira, M Carolina; Bishu, Shrinivas; Conti, Heather R; Gaffen, Sarah L

    2015-01-01

    Humans or mice subjected to immunosuppression, such as corticosteroids or anti-cytokine biologic therapies, are susceptible to mucosal infections by the commensal fungus Candida albicans. Recently it has become evident that the Th17/IL-17 axis is essential for immunity to candidiasis, but the downstream events that control immunity to this fungus are poorly understood. The CCAAT/Enhancer Binding Protein-β (C/EBPβ) transcription factor is important for signaling by multiple inflammatory stimuli, including IL-17. C/EBPβ is regulated in a variety of ways by IL-17, and controls several downstream IL-17 target genes. However, the role of C/EBPβ in vivo is poorly understood, in part because C/EBPβ-deficient mice are challenging to breed and work with. In this study, we sought to understand the role of C/EBPβ in the context of an IL-17-dependent immune response, using C. albicans infection as a model system. Confirming prior findings, we found that C/EBPβ is required for immunity to systemic candidiasis. In contrast, C/EBPβ(-/-) mice were resistant to oropharyngeal candidiasis (OPC), in a manner indistinguishable from immunocompetent WT mice. However, C/EBPβ(-/-) mice experienced more severe OPC than WT mice in the context of cortisone-induced immunosuppression. Expression of the antimicrobial peptide β-defensin (BD)-3 correlated strongly with susceptibility in C/EBPβ(-/-) mice, but no other IL-17-dependent genes were associated with susceptibility. Therefore, C/EBPβ contributes to immunity to mucosal candidiasis during cortisone immunosuppression in a manner linked to β-defensin 3 expression, but is apparently dispensable for the IL-17-dependent response.

  18. Pistacia lentiscus resin regulates intestinal damage and inflammation in trinitrobenzene sulfonic acid-induced colitis.

    Science.gov (United States)

    Gioxari, Aristea; Kaliora, Andriana C; Papalois, Apostolos; Agrogiannis, George; Triantafillidis, John K; Andrikopoulos, Nikolaos K

    2011-11-01

    Mastic (Pistacia lentiscus) of the Anacardiaceae family has exhibited anti-inflammatory and antioxidant properties in patients with Crohn's disease. This study was based on the hypothesis that mastic inhibits intestinal damage in inflammatory bowel disease, regulating inflammation and oxidative stress in intestinal epithelium. Four different dosages of P. lentiscus powder in the form of powder were administered orally to trinitrobenzene sulfonic acid-induced colitic rats. Eighty-four male Wistar rats were randomly assigned to seven groups: A, control; B, colitic; C-F, colitic rats daily supplemented with P. lentiscus powder at (C) 50 mg/kg, (D) 100 mg/kg, (E) 200 mg/kg, and (F) 300 mg/kg of body weight; and G, colitic rats treated daily with cortisone (25 μg/kg of body weight). Colonic damage was assessed microscopically. The cytokines tumor necrosis factor-α, intercellular adhesion molecule-1 (ICAM-1), interleukin (IL)-6, IL-8, and IL-10 and malonaldehyde were measured in colonic specimens. Results were expressed as mean ± SE values. Histological amelioration of colitis (P≤.001) and significant differences in colonic indices occurred after 3 days of treatment. Daily administration of 100 mg of P. lentiscus powder/kg of body weight decreased all inflammatory cytokines (P≤.05), whereas 50 mg of P. lentiscus powder/kg of body weight and cortisone treatment reduced only ICAM-1 (P≤.05 and P≤.01, respectively). Malonaldehyde was significantly suppressed in all treated groups (P≤.01). IL-10 remained unchanged. Cytokines and malonaldehyde remained unaltered after 6 days of treatment. Thus P. lentiscus powder could possibly have a therapeutic role in Crohn's disease, regulating oxidant/antioxidant balance and modulating inflammation.

  19. Attenuation of the cortisol response to stress in female rainbow trout chronically exposed to dietary selenomethionine

    Energy Technology Data Exchange (ETDEWEB)

    Wiseman, Steve, E-mail: steve.wiseman@usask.ca [Toxicology Centre, University of Saskatchewan, Saskatoon, SK, S7N 5B3 (Canada); Thomas, Jith K.; McPhee, Landon; Hursky, Olesya; Raine, Jason C. [Toxicology Centre, University of Saskatchewan, Saskatoon, SK, S7N 5B3 (Canada); Pietrock, Michael [Toxicology Centre, University of Saskatchewan, Saskatoon, SK, S7N 5B3 (Canada); Department of Veterinary Biomedical Sciences, University of Saskatchewan, Saskatoon, SK, S7N 5B3 (Canada); Giesy, John P. [Toxicology Centre, University of Saskatchewan, Saskatoon, SK, S7N 5B3 (Canada); Department of Veterinary Biomedical Sciences, University of Saskatchewan, Saskatoon, SK, S7N 5B3 (Canada); Department of Zoology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451 (Saudi Arabia); Department of Biology and Chemistry, City University of Hong Kong, Kowloon, Hong Kong (Hong Kong); School of Biological Sciences, University of Hong Kong, Hong Kong (Hong Kong); Department of Zoology, Center for Integrative Toxicology, Michigan State University, East Lansing, MI 48824 (United States); State Key Laboratory of Pollution Control and Resource Reuse and School of the Environment, Nanjing University, Nanjing (China); Hecker, Markus [Toxicology Centre, University of Saskatchewan, Saskatoon, SK, S7N 5B3 (Canada); School of Environment and Sustainability, University of Saskatchewan, Saskatoon, SK, S7N 5CB (Canada); Janz, David M. [Toxicology Centre, University of Saskatchewan, Saskatoon, SK, S7N 5B3 (Canada); Department of Veterinary Biomedical Sciences, University of Saskatchewan, Saskatoon, SK, S7N 5B3 (Canada)

    2011-10-15

    Highlights: Trout exposed to Se-Met had greater concentration of cortisol compared to controls. Transcript abundance of mc2r was greater in trout exposed to Se-Met. Trout exposed to Se-Met had a reduced cortisol response to a handling stressor. Cortisone concentration was greater in Se-Met exposed trout post-handling stressor. - Abstract: Selenomethionine (Se-Met) is the major dietary form of selenium (Se). While Se is a required nutrient, it can also influence the physiological stress response because it stimulates greater concentrations of cortisol in blood plasma of exposed fish. However, little is known about the effects of exposure to Se on the ability to cope with a secondary stressor. In the current study, female rainbow trout were exposed to an environmentally relevant dietary concentration (8.47 mg Se/kg dry mass (dm)) of Se-Met for 126 d, after which time fish were subjected to a 3-min handling stressor and sampled at 2 h and 24 h post-stressor exposure. Concentrations of cortisol, cortisone, glucose, and lactate in blood plasma and concentrations of glycogen and triglycerides in liver and muscle were determined. Abundances of transcripts of proteins involved in corticosteroidogenesis were determined using quantitative RT-PCR. Concentrations of cortisol were significantly greater in blood plasma of trout exposed to Se-Met, relative to control trout sampled prior to the handling stressor. A typical response of cortisol to the handling stressor was observed in the control trout. However, trout exposed to Se-Met were unable to mount a cortisol response to the handling stressor. Concentrations of cortisone, the inactive metabolite of cortisol, were significantly greater following the handling stressor in trout exposed to Se-Met. In trout exposed to Se-Met, transcript abundance of melanocortin 2 receptor (mc2r) and peripheral benzodiazepine receptor (pbr) were greater, which is consistent with the conclusion that synthesis of cortisol was greater. However

  20. Crystal Structure of Human Liver [delta][superscript 4]-3-Ketosteroid 5[beta]-Reductase (AKR1D1) and Implications for Substrate Binding and Catalysis

    Energy Technology Data Exchange (ETDEWEB)

    Di Costanzo, Luigi; Drury, Jason E.; Penning, Trevor M.; Christianson, David W. (UPENN); (UPENN-MED)

    2008-07-15

    AKR1D1 (steroid 5{beta}-reductase) reduces all {Delta}{sup 4}-3-ketosteroids to form 5{beta}-dihydrosteroids, a first step in the clearance of steroid hormones and an essential step in the synthesis of all bile acids. The reduction of the carbon-carbon double bond in an {alpha}{beta}-unsaturated ketone by 5{beta}-reductase is a unique reaction in steroid enzymology because hydride transfer from NADPH to the {beta}-face of a {Delta}{sup 4}-3-ketosteroid yields a cis-A/B-ring configuration with an {approx}90{sup o} bend in steroid structure. Here, we report the first x-ray crystal structure of a mammalian steroid hormone carbon-carbon double bond reductase, human {Delta}{sup 4}-3-ketosteroid 5{beta}-reductase (AKR1D1), and its complexes with intact substrates. We have determined the structures of AKR1D1 complexes with NADP{sup +} at 1.79- and 1.35-{angstrom} resolution (HEPES bound in the active site), NADP{sup +} and cortisone at 1.90-{angstrom} resolution, NADP{sup +} and progesterone at 2.03-{angstrom} resolution, and NADP{sup +} and testosterone at 1.62-{angstrom} resolution. Complexes with cortisone and progesterone reveal productive substrate binding orientations based on the proximity of each steroid carbon-carbon double bond to the re-face of the nicotinamide ring of NADP{sup +}. This orientation would permit 4-pro-(R)-hydride transfer from NADPH. Each steroid carbonyl accepts hydrogen bonds from catalytic residues Tyr{sup 58} and Glu{sup 120}. The Y58F and E120A mutants are devoid of activity, supporting a role for this dyad in the catalytic mechanism. Intriguingly, testosterone binds nonproductively, thereby rationalizing the substrate inhibition observed with this particular steroid. The locations of disease-linked mutations thought to be responsible for bile acid deficiency are also revealed.

  1. Hexose-6-phosphate dehydrogenase modulates 11beta-hydroxysteroid dehydrogenase type 1-dependent metabolism of 7-keto- and 7beta-hydroxy-neurosteroids.

    Directory of Open Access Journals (Sweden)

    Lyubomir G Nashev

    Full Text Available BACKGROUND: The role of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1 in the regulation of energy metabolism and immune system by locally reactivating glucocorticoids has been extensively studied. Experiments determining initial rates of enzyme activity revealed that 11beta-HSD1 can catalyze both the reductase and the dehydrogenase reaction in cell lysates, whereas it predominantly catalyzes the reduction of cortisone to cortisol in intact cells that also express hexose-6-phosphate dehydrogenase (H6PDH, which provides cofactor NADPH. Besides its role in glucocorticoid metabolism, there is evidence that 11beta-HSD1 is involved in the metabolism of 7-keto- and 7-hydroxy-steroids; however the impact of H6PDH on this alternative function of 11beta-HSD1 has not been assessed. METHODOLOGY: We investigated the 11beta-HSD1-dependent metabolism of the neurosteroids 7-keto-, 7alpha-hydroxy- and 7beta-hydroxy-dehydroepiandrosterone (DHEA and 7-keto- and 7beta-hydroxy-pregnenolone, respectively, in the absence or presence of H6PDH in intact cells. 3D-structural modeling was applied to study the binding of ligands in 11beta-HSD1. PRINCIPAL FINDINGS: We demonstrated that 11beta-HSD1 functions in a reversible way and efficiently catalyzed the interconversion of these 7-keto- and 7-hydroxy-neurosteroids in intact cells. In the presence of H6PDH, 11beta-HSD1 predominantly converted 7-keto-DHEA and 7-ketopregnenolone into their corresponding 7beta-hydroxy metabolites, indicating a role for H6PDH and 11beta-HSD1 in the local generation of 7beta-hydroxy-neurosteroids. 3D-structural modeling offered an explanation for the preferred formation of 7beta-hydroxy-neurosteroids. CONCLUSIONS: Our results from experiments determining the steady state concentrations of glucocorticoids or 7-oxygenated neurosteroids suggested that the equilibrium between cortisone and cortisol and between 7-keto- and 7-hydroxy-neurosteroids is regulated by 11beta-HSD1 and greatly

  2. Glucocorticoid regulation of food-choice behavior in humans: Evidence from Cushing’s syndrome

    Directory of Open Access Journals (Sweden)

    Scott J Moeller

    2016-02-01

    Full Text Available The mechanisms by which glucocorticoids regulate food intake and resulting body mass in humans are not well-understood. One potential mechanism could involve modulation of reward processing, but human stress models examining effects of glucocorticoids on behavior contain important confounds. Here, we studied individuals with Cushing’s syndrome, a rare endocrine disorder characterized by chronic excess endogenous glucocorticoids. Twenty-three patients with Cushing’s syndrome (13 with active disease; 10 with disease in remission and 15 controls with a comparably high body mass index completed two simulated food-choice tasks (one with ‘explicit’ task contingencies and one with ‘probabilistic’ task contingencies, during which they indicated their objective preference for viewing high calorie food images versus standardized pleasant, unpleasant, and neutral images. All participants also completed measures of food craving, and approximately half of the participants provided 24-hour urine samples for assessment of cortisol and cortisone concentrations. Results showed that on the explicit task (but not the probabilistic task, participants with active Cushing’s syndrome made fewer food-related choices than participants with Cushing’s syndrome in remission, who in turn made fewer food-related choices than overweight controls. Corroborating this group effect, higher urine cortisone was negatively correlated with food-related choice in the subsample of all participants for whom these data were available. On the probabilistic task, despite a lack of group differences, higher food-related choice correlated with higher state and trait food craving in active Cushing’s patients. Taken together, relative to overweight controls, Cushing’s patients, particularly those with active disease, displayed a reduced vigor of responding for food rewards that was presumably attributable to glucocorticoid abnormalities. Beyond Cushing’s, these results

  3. Glucocorticoid and androgen signaling pathways diverge between advertisement calling and non-calling fish.

    Science.gov (United States)

    Genova, Rachel M; Marchaterre, Margaret A; Knapp, Rosemary; Fergus, Daniel; Bass, Andrew H

    2012-09-01

    Behavioral and neuroendocrine mechanisms of social vocalization in teleost fish are influenced by the glucocorticoid cortisol and the androgen 11-ketotestosterone (11kT). The relative abundance of both 11kT, which binds to androgen receptors (ARα, ARβ), and cortisol, which binds to glucocorticoid receptors (GR-1, GR-2), is regulated by 11β-hydroxylase (11βH) that converts 11-deoxycortisol to cortisol and testosterone to 11β-OH-testosterone, and 11β-hydroxysteroid dehydrogenase (11βHSD) that converts cortisol to the inactive metabolite cortisone and 11β-OH-testosterone to 11kT. In midshipman fish, we tested the hypothesis that plasma steroid levels, mRNA abundance for 11βH and 11βHSD in the vocal muscle and testis (known site of 11kT synthesis), and mRNA abundances for ARs and GRs in vocal muscle, would differ between males that did or did not recently produce 'hum' advertisement calls. Quantitative real-time PCR demonstrated that non-calling male vocal muscle had significantly higher mRNA levels for all receptors except ARα, and a strong trend for higher 11βHSD; 11βH was similar to that in calling males. Calling males had higher plasma and testis 11kT, but lower plasma cortisol, levels. Testis enzyme levels did not differ between male groups, although calling males showed a positive linear correlation between plasma 11kT and testis 11βHSD mRNA levels, consistent with testis being the main source of plasma 11kT. We propose that higher vocal muscle 11βHSD levels in non-calling males reflect increased local conversion of elevated cortisol to cortisone, providing protection from cortisol-related toxicity, while increased receptor expression in non-calling males functions as a preparatory mechanism for meeting the physiological demands of future vocalization. Copyright © 2012 Elsevier Inc. All rights reserved.

  4. Lack of significant metabolic abnormalities in mice with liver-specific disruption of 11β-hydroxysteroid dehydrogenase type 1.

    LENUS (Irish Health Repository)

    Lavery, Gareth G

    2012-07-01

    Glucocorticoids (GC) are implicated in the development of metabolic syndrome, and patients with GC excess share many clinical features, such as central obesity and glucose intolerance. In patients with obesity or type 2 diabetes, systemic GC concentrations seem to be invariably normal. Tissue GC concentrations determined by the hypothalamic-pituitary-adrenal (HPA) axis and local cortisol (corticosterone in mice) regeneration from cortisone (11-dehydrocorticosterone in mice) by the 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzyme, principally expressed in the liver. Transgenic mice have demonstrated the importance of 11β-HSD1 in mediating aspects of the metabolic syndrome, as well as HPA axis control. In order to address the primacy of hepatic 11β-HSD1 in regulating metabolism and the HPA axis, we have generated liver-specific 11β-HSD1 knockout (LKO) mice, assessed biomarkers of GC metabolism, and examined responses to high-fat feeding. LKO mice were able to regenerate cortisol from cortisone to 40% of control and had no discernible difference in a urinary metabolite marker of 11β-HSD1 activity. Although circulating corticosterone was unaltered, adrenal size was increased, indicative of chronic HPA stimulation. There was a mild improvement in glucose tolerance but with insulin sensitivity largely unaffected. Adiposity and body weight were unaffected as were aspects of hepatic lipid homeostasis, triglyceride accumulation, and serum lipids. Additionally, no changes in the expression of genes involved in glucose or lipid homeostasis were observed. Liver-specific deletion of 11β-HSD1 reduces corticosterone regeneration and may be important for setting aspects of HPA axis tone, without impacting upon urinary steroid metabolite profile. These discordant data have significant implications for the use of these biomarkers of 11β-HSD1 activity in clinical studies. The paucity of metabolic abnormalities in LKO points to important compensatory effects by HPA

  5. 11β-Hydroxysteroid dehydrogenase type 1: relevance of its modulation in the pathophysiology of obesity, the metabolic syndrome and type 2 diabetes mellitus.

    Science.gov (United States)

    Pereira, C D; Azevedo, I; Monteiro, R; Martins, M J

    2012-10-01

    Recent evidence strongly argues for a pathogenic role of glucocorticoids and 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in obesity and the metabolic syndrome, a cluster of risk factors for atherosclerotic cardiovascular disease and type 2 diabetes mellitus (T2DM) that includes insulin resistance (IR), dyslipidaemia, hypertension and visceral obesity. This has been partially prompted not only by the striking clinical resemblances between the metabolic syndrome and Cushing's syndrome (a state characterized by hypercortisolism that associates with metabolic syndrome components) but also from monogenic rodent models for the metabolic syndrome (e.g. the leptin-deficient ob/ob mouse or the leptin-resistant Zucker rat) that display overall increased secretion of glucocorticoids. However, systemic circulating glucocorticoids are not elevated in obese patients and/or patients with metabolic syndrome. The study of the role of 11β-HSD system shed light on this conundrum, showing that local glucocorticoids are finely regulated in a tissue-specific manner at the pre-receptor level. The system comprises two microsomal enzymes that either activate cortisone to cortisol (11β-HSD1) or inactivate cortisol to cortisone (11β-HSD2). Transgenic rodent models, knockout (KO) for HSD11B1 or with HSD11B1 or HSD11B2 overexpression, specifically targeted to the liver or adipose tissue, have been developed and helped unravel the currently undisputable role of the enzymes in metabolic syndrome pathophysiology, in each of its isolated components and in their prevention. In the transgenic HSD11B1 overexpressing models, different features of the metabolic syndrome and obesity are replicated. HSD11B1 gene deficiency or HSD11B2 gene overexpression associates with improvements in the metabolic profile. In face of these demonstrations, research efforts are now being turned both into the inhibition of 11β-HSD1 as a possible pharmacological target and into the role of dietary habits on the

  6. Effects of corticosteroids and splenectomy on the immune clearance and destruction of erythrocytes.

    Science.gov (United States)

    Atkinson, J P; Schreiber, A D; Frank, M M

    1973-06-01

    Corticosteroids and splenectomy constitute two important therapeutic modalities in the treatment of autoimmune hemolytic anemia. Each of these may affect both the rate of synthesis of autoantibody and the clearance of antibody sensitized cells. The latter possibility has been examined in an experimental model which allows evaluation of the role of antibody and complement in the immune clearance of erythrocytes in molecular terms. The in vivo clearance of (51)Cr-labeled guinea pig erythrocytes sensitized with purified rabbit IgG or IgM antibody to produce a known number of complement-fixing sites per cell was studied. Corticosteroid therapy increased the survival of both IgG and IgM sensitized erythrocytes by decreasing sequestration in the reticuloendothelial system (RES). 5 days of therapy prior to injection of antibody coated cells were required for a maximal effect. It appeared that the RES of cortisone-treated animals had a lowered sensitivity to erythrocytes coated with antibody and complement and the cells were removed as though they were coated with fewer complement sites/cell. The general pattern and kinetics of clearance and the localization of sequestered cells were not modified by corticosteroids. As the number of IgG C1-fixing sites was increased, the difference betwen cortisone treated and control animals was less marked. Splenectomy led to an increased survival of IgG-coated cells and a sixfold increase in IgG C1-fixing sites was necessary in order to obtain similar rates of clearance in splenectomized and control animals. The liver was responsible for this much less efficient clearance of cells in splenectomized animals: the clearance pattern was typical of that noted for IgG. No effect at all was noted on the clearance of IgM sensitized cells in splenectomized animals. These experiments clearly demonstrate that both corticosteroid therapy and splenectomy act to decrease the in vivo clearance of IgG-sensitized cells: only corticosteroids alter the

  7. A switch in hepatic cortisol metabolism across the spectrum of non alcoholic fatty liver disease.

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    Adeeba Ahmed

    Full Text Available CONTEXT: Non alcoholic fatty liver disease (NAFLD is the hepatic manifestation of the metabolic syndrome. NAFLD represents a spectrum of liver disease ranging from reversible hepatic steatosis, to non alcoholic steato-hepatitis (NASH and cirrhosis. The potential role of glucocorticoids (GC in the pathogenesis of NAFLD is highlighted in patients with GC excess, Cushing's syndrome, who develop central adiposity, insulin resistance and in 20% of cases, NAFLD. Although in most cases of NAFLD, circulating cortisol levels are normal, hepatic cortisol availability is controlled by enzymes that regenerate cortisol (F from inactive cortisone (E (11β-hydroxysteroid dehydrogenase type 1, 11β-HSD1, or inactivate cortisol through A-ring metabolism (5α- and 5β-reductase, 5αR and 5βR. OBJECTIVE AND METHODS: In vitro studies defined 11β-HSD1 expression in normal and NASH liver samples. We then characterised hepatic cortisol metabolism in 16 patients with histologically proven NAFLD compared to 32 obese controls using gas chromatographic analysis of 24 hour urine collection and plasma cortisol generation profile following oral cortisone. RESULTS: In patients with steatosis 5αR activity was increased, with a decrease in hepatic 11β-HSD1 activity. Total cortisol metabolites were increased in this group consistent with increased GC production rate. In contrast, in patients with NASH, 11β-HSD1 activity was increased both in comparison to patients with steatosis, and controls. Endorsing these findings, 11β-HSD1 mRNA and immunostaining was markedly increased in NASH patients in peri septal hepatocytes and within CD68 positive macrophages within inflamed cirrhotic septa. CONCLUSION: Patients with hepatic steatosis have increased clearance and decreased hepatic regeneration of cortisol and we propose that this may represent a protective mechanism to decrease local GC availability to preserve hepatic metabolic phenotype. With progression to NASH, increased 11

  8. Differential protective effects of immune lymphoid cells against transplanted line Ib leukemia and immune polioencephalomyelitis. [X radiation, mice

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    Duffey, P.S.; Lukasewycz, O.A.; Olson, D.S.; Murphy, W.H.

    1978-12-01

    The capacity of immune cells obtained from the major lymphoid compartments to protect C58 mice from transplanted line Ib leukemia, and from an age-dependent autoimmune CNS disease (immune polioencephalomyelitis = IPE) elicited by immunizing old C58 mice with inactivated Ib cells was quantified. Cells used for comparative adoptive protection tests were harvested from the major lymphoid compartments 14 to 15 days after young C58 mice were immunized with inactivated Ib cell preparations. Regression curves were plotted from survival data and the log/sub 10/PD/sub 50/ values were determined. Immune spleen (ISC) and peritoneal cells (IPEC) were significantly more protective against transplanted Ib cells than immune lymph node (ILNC), thymic (ITC), and marrow cells (IMC). In contrast, IPEC and IMC were not protective against IPE and ITC were only marginally protective. ILNC afforded significant protection to transplantable leukemia but were only marginally protective to IPE. When ISC were treated with anti-thy 1.2 serum and complement, protection against transplanted leukemia and IPE was reduced > 99%. When donors of immune lymphoid cells were treated with 12.5 mg of cortisone acetate daily for 2 days before lymphoid cells were harvested, protection against transplanted Ib cells by ISC was reduced by approximately 90% whereas protection against IPE was totally eliminated. Considered together, these results indicate that the protective mechanisms to transplantable leukemia and IPE differ significantly in the same indicator mouse strain.

  9. Incidentally detected Castleman disease in a patient with allergic rhinosinu sitis

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    Stojšić Jelena

    2008-01-01

    Full Text Available INTRODUCTION Castleman disease was for the first time described in 1956 as a mediastinal tumour mass. Etiology of this disease is still unknown. The disease can be solitary and multicentric or rarely of a mixed type. The former is often of hyaline vascular type, while the latter is of plasma cell type. CASE REPORT Castleman disease was diagnosed in a 26-year old male patient when a well defined shadow was incidentally detected in the middle lobe of the right lung. A year before, he was diagnosed with allergic rhinitis to Ambrosia. Two years after surgery the patient was feeling well, and was without any recurrence, however, allergic rhinitis still persisted. CONCLUSION Castleman disease can occur in any organ containing lymph tissues. Most frequently the disease is described as mediastinal, rarely as an intrapulmonary tumorous mass, and it is most frequently seen in younger persons. The solitary type of Castleman disease is surgical treatable with a prospect of good prognosis, while the multicentric and mixed types recur despite treatment with cortisone, irradiation and cytostatics. As the association between Castleman disease and allergic diseases has not been confirmed up-tonow, it could be concluded that this patient suffered from two separated diseases.

  10. Metabolic Signatures of Kidney Yang Deficiency Syndrome and Protective Effects of Two Herbal Extracts in Rats Using GC/TOF MS

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    Linjing Zhao

    2013-01-01

    Full Text Available Kidney Yang Deficiency Syndrome (KDS-Yang, a typical condition in Chinese medicine, shares similar clinical signs of the glucocorticoid withdrawal syndrome. To date, the underlying mechanism of KDS-Yang has been remained unclear, especially at the metabolic level. In this study, we report a metabolomic profiling study on a classical model of KDS-Yang in rats induced by hydrocortisone injection to characterize the metabolic transformation using gas chromatography/time-of-flight mass spectrometry. WKY1, a polysaccharide extract from Astragalus membranaceus and Lycium barbarum, and WKY2, an aqueous extract from a similar formula containing Astragalus membranaceus, Lycium barbarum, Morinda officinalis, Taraxacum mongolicum, and Cinnamomum cassia presl, were used separately for protective treatments of KDS-Yang. The changes of serum metabolic profiles indicated that significant alterations of key metabolic pathways in response to abrupt hydrocortisone perturbation, including decreased energy metabolism (lactic acid, acetylcarnitine, lipid metabolism (free fatty acids, 1-monolinoleoylglycerol, and cholesterol, gut microbiota metabolism (indole-3-propionic acid, biosynthesis of catecholamine (norepinephrine, and elevated alanine metabolism, were attenuated or normalized with different degrees by the pretreatment of WKY1 or WKY2, which is consistent with the observations in which the two herbal agents could ameliorate biochemical markers of serum cortisone, adrenocorticotropic (ACTH, and urine 17-hydroxycorticosteroids (17-OHCS.

  11. Mechanisms of ozone-induced bronchial hyperreactivity to muscarinic agonists in the guinea pig

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    Roum, J.H.

    1986-01-01

    Bronchial hyperreactivity, a chief characteristic of asthma, is poorly understood mechanistically. Its development in ozone-exposed guinea pigs was studied in this dissertation research. Reactivity was assessed in awake, spontaneously breathing animals by measuring specific airway resistance (SRaw) as a function of increasing muscarinic bronchoconstrictor challenge. In the first study, improvements in the reactivity measurement were seen by using (1) propranolol pretreatment (10 mg/kg IP, 1/2 hr before measurement) and (2) intravenous (rather than aerosolized) muscarinic challenge. Both (1) decreased its population wide variation and (2) increased its intra-animal reproducibility. Secondly, characteristics of ozone-induced bronchial hyperreactivity, such as (1) its airway mucosal permeability dependence, (2) its time course of development, and (3) its ozone-dose dependence were studied. The relationship between airway mucosa neutrophilic infiltration and the development of this hyperreactivity was examined in the third and fourth study. In the third, a time course study showed that development of hyperreactivity occurred before the neutrophilic infiltration phase, and correlated best with a decrease in identifiable mucosal goblet cells and increase in identifiable mucosoal mast cells. In the fourth, the development of ozone-induced hyperreactivity in animals made granulocytopenic with cyclophosphamide and cortisone acetate treatment was studied. In the final study, the effects of indomethacin on the development of this hyperreactivity was assessed.

  12. Evaluation in mice of the capillary leak syndrome (CLS) mediated by the systemic administration of recombinant interleukin-2 (IL-2)

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    Ettinghausen, S.E.; Rosenstein, M.; Rosenberg, S.A.

    1986-03-01

    Since a CLS with interstitial pulmonary edema has been the major toxicity of IL-2 administration in humans, the authors studied this CLS in mice by quantitating the IL-2 mediated, tissue extravasation (Ex) of intravenously injected /sup 125/I-bovine serum albumin (BSA). Mice received saline (HBSS) or 200,000 U of IL-2 intraperitoneally thrice daily from day 0-6 before tissues were counted. A permeability index (PI) was calculated by dividing the mean counts per minute (CPM) from tissues of treated mice by those from controls. In a representative experiment, increased BSA Ex was noted in the lungs of mice treated with IL-2 when compared with HBSS (6187 +/- 141 and 638 +/- 64 CPM +/- SEM, respectively; p2 < .001; PI = 9.7). Other tissues with increased BSA Ex included the liver, spleen, kidneys and mesenteric lymph nodes (PI = 6.7, 10.0, 6.3, 6.0, respectively). BSA Ex, which did not occur with the excipient control, was dependent upon the dose and the duration of IL-2. Serial lung weights showed dramatic increases in water weight induced by IL-2. Treatment of mice with radiation (500R), cyclophosphamide, or cortisone acetate significantly reduced IL-2 mediated BSA Ex. Thus, IL-2 induced a generalized CLS which is mediated directly or indirectly by cellular mechanisms.

  13. Mielolipoma adrenal bilateral asociado a disfunción endocrina Bilateral adrenal myelolipoma associated with an endocrine dysfunction

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    Omaida F. Torres Herrera

    2010-08-01

    Full Text Available Se presentó un caso de mielolipoma adrenal bilateral asociado a hiperplasia adrenal congénita por déficit de enzima 21 hidroxilasa en un joven de 27 años de edad, que abandonó tratamiento sustitutivo con acetato de cortisona a los 14 años. Estuvo asintomático hasta su ingreso en el hospital, al cual es remitido por dolor abdominal, vómitos y fiebre, constatándose tumoración abdominal gigante en hemiabdomen izquierdo. Las características clínicas, hormonales y radiológicas halladas son comentadas y correlacionadas con lo registrado en la literatura médica. Hasta donde se revisó, es el primer caso de mielolipoma adrenal bilateral asociado a disfunción endocrina que se publica en Cuba.Authors present a case of bilateral adrenal myelolipoma associated with a congenital adrenal hyperplasia by deficit of hydroxilase enzyme 21 in a young aged 27 who leaves the substitution treatment with cortisone acetate at 14 years old. He was asymptomatic until its hospital admission due to abdominal pain, vomiting and fever and a high abdominal tumor in left hemi-abdomen. Clinical hormonal and radiological features founded are discussed and correlated with those registered in medical literature. As far as we know, this is the first case of bilateral adrenal myelolipoma associated with an endocrine dysfunction published in Cuba.

  14. Development of an assay for urinary free cortisol determination on the Technicon Immuno 1 system

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    Letellier, M.; Levesque, A.; Daigle, F. [Centre Universitaire de Sante de l' Estrie, Dept. of Clinical Biochemistry, Site Fleurimont, Sherbrooke, Quebec (Canada)

    1997-08-15

    To develop and evaluate a method using an ethyl acetate extraction procedure for the determination of urinary free cortisol on the Technicon Immuno 1 system from Bayer Corporation. We tested the assay precision, linearity, and correlation with the Urinary Kallestad Quanticoat Cortisol radioimmunoassay. We also studied the efficiency of the extraction procedure, performed a cross-reactivity study with different cortisol metabolites, and determined the reference values. The assay shows within-run CVs varying from 1.6 to 5.3% and between-day CVs from 2.7 to 6.1% for urinary free cortisol concentrations from 58 to 1097 nmol/L. The assay demonstrates an excellent linearity and a very good correlation with the Kallestad Quanticoat Cortisol assay (slope 0.94, y-intercept = 29 nmol/L, Sy|x = 54 nmol/L, r = 0.996). The reference values were estimated at 42-281 nmol/d. The extraction procedure shows an average recovery of 99.0% and minimal interference with the cortisol metabolites tested with the exception of cortisone. The evaluation shows that the developed assay has the analytical characteristics required for its utilization in a clinical laboratory. (author)

  15. Radioimmunoimaging of pneumocystis carinii infection in rats

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    Vallabhajosula, S.; Shane, L.B.; Goldsmith, S.J.; Lipszyc, H.; Walzer, P.

    1984-01-01

    Pneumocystis carinil pneumonia (PCP) is seen in patients with impaired immunity due to chemotherapeutic suppression or to a primary disorder, congenital or AIDS. Although radiogallium imaging has been helpful in the workup of PCP, it is non-specific. Since there is no early specific non-invasive method to diagnose PCP, the authors are developing an imaging technique using radiolabeled antibodies. Fulminant PCP was induced in rats by injecting cortisone, 20mg 2-3 times/wk for 8 wks. PC cells isolated from rat lung were injected into rabbits. The antiserum thus derived was separated and purified using Protein-A bound sepharose column with identification of IgG by polyacrylamide gel electrophoresis. Both rabbit antipneumocystis antibodies and purified IgG(Sigma) were iodinated with I-131 to a high specific activity (3-5..mu..Ci/ug) using a lactoperoxidase method. /sup 131/I-labeled specific and non-specific IgG were injected into rats with PC infection and imaged with an Anger camera. After sacrifice, I-131 activity/gram tissue (lung, liver, heart) was determined and expressed as organ ratios. An increased uptake of specific antibody in lungs of rats with PCP was demonstrated by organ counting and imaging. This increase was not seen in normal controls or rats injected with non-specific IgG. These data provide a basis for radioimmunoimaging of infectious diseases.

  16. Angina monocitica con sovrainfezione da Prevotella denticola: caso clinico

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    Maria Teresa Allù

    2005-06-01

    Full Text Available Monocytic angina with superinfection of Prevotella denticola: clinical case Monocytic angina is a clinical sindrome caused by Epstein-Barr virus characterized by fever, pharyngitis, exudative tonsillitis, swollen lymphoglands, splenomegaly and hepatomegaly.The inflamed pharynx and necrotic tonsils of infectious mononucleosis are subject to bacterial superinfection initially or during the course of the illness; the reduced PO2 tension and low oxidation-reduction potential that prevail in a vascular and necrotic tissues favour the growth of anaerobes. In this article we reported the clinical case of a ten years old children, who presented fever and tonsillopharyngitis; he was treated with cefotaxime and piperacillin, he did not improve in health. He was admitted to hospital (Department of Otorhinolaryngology. The patient was treated with aminoglycoside (tobramycin, piperacillin and cortisone; the clinical situation deteriorated. Pus sample was collected from the tonsils and cultured. Isolated strain from culture anaerobic was identified biochemically (Rapid-ID32ANA.The microorganism isolated was: Prevotella denticola (oral anaerobic gram-negative rods; β-lactamase production was tested by using the chromogenic cephalosporin disk test.The susceptibility to antibiotics was performed according to NCCLS recommendations. Prevotella denticola (β-lactamase production was resistant to penicillin, cefoxitin, cefotetan, piperacillin, clindamycin and metronidazole it was susceptible to piperacillin-tazobactam, amoxicillin-clavulanate, ticarcillin-clavulanate, imipenem and chloramphenicol. Children was treated with piperacillin-tazobactam, with rapid symptomatic relief.

  17. Femoral head blood flow in long-term steroid therapy: study of rabbit model

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    Wang, G.J.; Hubbard, S.L.; Reger, S.I.; Miller, E.D.; Stamp, W.G.

    1983-12-01

    Using a rabbit model, previous studies showed steroid-induced hyperlipidemia with subsequent fatty embolization of the subchondral arteries and hypertrophy of the marrow fat cells, followed by elevation of femoral head pressure from the normal level of 25 cm to nearly 60 cm H2O after eight weeks of treatment. This has led us to believe that pressure changes lead to decreased blood flow in the femoral head. In our study of 22 New Zealand white adult rabbits, weighing an average of 4.0 kg, 14 received a weekly dose of 12.45 mg of methylprednisolone (Depo-Medrol), and eight served as control. Femoral head blood flow was established using the radioactive microsphere technique. Control and cortisone-treated rabbits had femoral head blood flow measured 6, 8 and 10 weeks after treatment. The average blood flow in the control femoral heads averaged 0.2039 +/- 0.076 ml/min/gm, with no difference in the left side and the right side. In the treated group, the average blood flow at ten weeks was 0.162 +/- 0.039 ml/min/gm on the right and 0.164 +/- 0.037 ml/min/gm on the left, which was significantly different. This is parallel to unpredictable clinical findings in human beings.

  18. Gender-dependent association of HSD11B1 single nucleotide polymorphisms with glucose and HDL-C levels

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    Luciane Viater Turek

    2014-09-01

    Full Text Available In this study, we investigated the influence of two SNPs (rs846910 and rs12086634 of the HSD11B1 gene that encodes 11β-hydroxysteroid dehydrogenase type 1(11β-HSD1, the enzyme that catalyzes the conversion of cortisol to cortisone, on variables associated with obesity and metabolic syndrome in 215 individuals of both sexes from southern Brazil. The HSD11B1 gene variants were genotyped using the TaqMan SNP genotyping assay. Glucose, triglycerides, total cholesterol, HDL-cholesterol and LDL-cholesterol were measured by standard automated methods. Significant results were found in women, with carriers of the G allele of SNP rs12086634 having higher glucose levels than non-carriers. Carriers of the A allele of SNP rs846910 had higher levels of HDL-cholesterol. The involvement of both polymorphisms as independent factors in determining the levels of glucose and HDL-cholesterol was confirmed by multiple regression analysis (β = 0.19 ± 0.09, p = 0.03 and β = 0.22 ± 0.10, p = 0.03, respectively. Our findings suggest that the HSD11B1SNPs studied may indirectly influence glucose and HDL-cholesterol metabolism in women, possibly through down-regulation of the HSD11B1 gene by estrogen.

  19. Corticoids: 60 Years Later a Pending Subject

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    Silvia Gómez Ordóñez

    2007-12-01

    Full Text Available The objective of this article is to make a brief compilation of the physiology of the hypothalamic-pituitary-adrenal axis in order to understandthe role of the exogenous corticoids as therapeutic tools in innumerable pathologies, but when used inappropriately, it can produce important deleterious effects. The history of the corticoids began 164 years ago in 1843 when Thomas Addison described the symptoms of the adrenal gland insufficiency. On September 21st 1948, almost one hundred years after, Dr. Hench injected cortisone for the first time in a patient with arthritis. In 1950 Hench, Kendall and Reichsteinreceived the Nobel Prize in Medicine and Physiology. In the cortex of the adrenal glands, three different hormones are synthesized from cholesterol, and these hormones produce diverseeffects on the homeostasis of the body. The synthetic glucocorticoids are classified by their anti-inflammatory power, half life, and mineralocorticoideffect; they operate in almost every cell through genomic and non genomic mechanismsof action producing different responses. This is the reason of their wide therapeutic effect in respiratory diseases like asthma and COPD,multiple sclerosis, rejection of transplants, among others.

  20. Identification of Important Chemical Features of 11β-Hydroxysteroid Dehydrogenase Type1 Inhibitors: Application of Ligand Based Virtual Screening and Density Functional Theory

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    Keun Woo Lee

    2012-04-01

    Full Text Available 11ß-Hydroxysteroid dehydrogenase type1 (11ßHSD1 regulates the conversion from inactive cortisone to active cortisol. Increased cortisol results in diabetes, hence quelling the activity of 11ßHSD1 has been thought of as an effective approach for the treatment of diabetes. Quantitative hypotheses were developed and validated to identify the critical chemical features with reliable geometric constraints that contribute to the inhibition of 11ßHSD1 function. The best hypothesis, Hypo1, which contains one-HBA; one-Hy-Ali, and two-RA features, was validated using Fischer’s randomization method, a test and a decoy set. The well validated, Hypo1, was used as 3D query to perform a virtual screening of three different chemical databases. Compounds selected by Hypo1 in the virtual screening were filtered by applying Lipinski’s rule of five, ADMET, and molecular docking. Finally, five hit compounds were selected as virtual novel hit molecules for 11ßHSD1 based on their electronic properties calculated by Density functional theory.

  1. Dynamic immune cell recruitment after murine pulmonary Aspergillus fumigatus infection under different immunosuppressive regimens

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    Natarajaswamy Kalleda

    2016-07-01

    Full Text Available Humans are continuously exposed to airborne spores of the saprophytic fungus Aspergillus fumigatus. However, in healthy individuals pulmonary host defense mechanisms efficiently eliminate the fungus. In contrast, A. fumigatus causes devastating infections in immunocompromised patients. Host immune responses against A. fumigatus lung infections in immunocompromised conditions have remained largely elusive. Given the dynamic changes in immune cell subsets within tissues upon immunosuppressive therapy, we dissected the spatiotemporal pulmonary immune response after A. fumigatus infection to reveal basic immunological events that fail to effectively control invasive fungal disease. In different immunocompromised murine models, myeloid, notably neutrophils and macrophages, but not lymphoid cells were strongly recruited to the lungs upon infection. Other myeloid cells, particularly dendritic cells and monocytes, were only recruited to lungs of corticosteroid treated mice, which developed a strong pulmonary inflammation after infection. Lymphoid cells, particularly CD4+ or CD8+ T-cells and NK cells were highly reduced upon immunosuppression and not recruited after A. fumigatus infection. Moreover, adoptive CD11b+ myeloid cell transfer rescued cyclophosphamide immunosuppressed mice from lethal A. fumigatus infection but not cortisone and cyclophosphamide immunosuppressed mice. Our findings illustrate that CD11b+ myeloid cells are critical for anti-A. fumigatus defense under cyclophosphamide immunosuppressed conditions.

  2. Eosinophilic Granuloma of a Child

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    Ozgur Demir

    2016-12-01

    Full Text Available Eosinophilic granuloma is part of Langerhans' cell histiocytosis. It is a rare, benign bone tumor, often involving the head bones. Most patients present between 5 and 15 years of age. Lesions of eosinophilic granuloma may disappear spontaneously. Painful lesions can be treated with radiotherapy, chemotherapy, surgical curettage of the tumor or local infusion of cortisone. A six year old girl presented to our clinic with severe painful swelling on the right parietal region with a gradual increase in size and frequent episodes of headache for 2 months. Radiological findings demonstrated right parietal cranial lytic lesion with intra and extracranial extension. The patient was treated with gross total excision of tumor and cranioplasty without any adjuvant therapy. Histopathology of the tumor showed cellular components of Langerhan' cells admixed with chronic cellular infiltrate and eosinophils. Findings were consistent with eosinophillic granuloma. The patient recovered well with no known recurrence till date. There is no definitive treatment option for this disorder. Treatment option may be changed depending on the extent of the disease and the symptoms. We recommend surgical excision in the presence of intracranial extension of painful lesion. [J Contemp Med 2016; 6(4.000: 343-347

  3. Bronchial hyperreactivity occurs in steroid-treated guinea pigs depleted of leukocytes by cyclophosphamide

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    Murlas, C.; Roum, J.H.

    1985-05-01

    The effects of cyclophosphamide and cortisone acetate treatment on O/sub 3/-induced changes in airway mucosal morphology and bronchial reactivity were assessed in guinea pigs. Animals in groups of four were studied at 2 or 6 h after O/sub 3/ (3.0 ppm, 2 h) and in one control group. Reactivity was determined by measuring specific airway resistance during intravenous acetylcholine infusion in intact, unanesthetized, spontaneously breathing animals. After testing, tracheal tissue was obtained from all animals for light microscopic examination. Another group of 10 drug-treated and 10 normal animals were tested at 2 h, 6 h, 1 day, and 4 days after O/sub 3/. Drug treatment resulted in substantial decreases in both circulating and airway mucosal granulocytes. Two hours after O/sub 3/, a marked decrease in airway mucosal goblet cells as well as ciliated cell damage occurred in both normal and treated animals. However, only in normal animals did neutrophilic infiltration develop thereafter. Nonetheless, hyperreactivity postozone occurred and progressed similarly in both groups. Our results indicate that acute O/sub 3/-induced bronchial hyperreactivity at 2 h is associated with signs of airway mucosal injury but appears independent of granulocyte changes. Airway neutrophilic infiltration and eosinophil depletion seem to be consequences of mucosal injury from O/sub 3/ and not causes of the bronchial hyperreactivity that results.

  4. Immunotherapy of murine leukemia. VIII. Efficacy of passive serum therapy of Friend leukemia virus-induced disease in immunocompromised mice

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    Genovesi, E.V.; Livnat, D.; Collins, J.J.

    1983-02-01

    Previous studies have demonstrated that the passive therapy of Friend murine leukemia virus (F-MuLV)-induced disease with chimpanzee anti-F-MuLV serum is accompanied by the development of host antiviral humoral and cellular immunity, the latter measurable in adoptive transfer protocols and by the ability of serum-protected mice to resist virus rechallenge. The present study was designed to further examine the contribution of various compartments of the host immune system to serum therapy itself, as well as to the acquired antiviral immunity that develops in serum-protected mice, through the use of naturally immunocompromised animals (e.g., nude athymic mice and natural killer (NK)-deficient beige mutant mice) or mice treated with immunoabrogating agents such as sublethal irradiation, cyclophosphamide (Cytoxan (Cy)), cortisone, and /sup 89/Sr. The studies in nude mice indicate that while mature T-cells are not needed for effective serum therapy, they do appear to be necessary for the long-term resistance of serum-protected mice to virus rechallenge and for the generation of the cell population(s) responsible for adoptive transfer of antiviral immunity. Lastly, while the immunocompromise systems examined did effect various host antiviral immune responses, none of them, including the NK-deficient beige mutation, significantly diminished the efficacy of the passive serum therapy of F-MuLV-induced disease.

  5. Comparative evaluation of the results following palliative radiotherapy of cerebral metastases from mammary and bronchial carcinomas. Vergleich der Therapieergebnisse bei palliativer Strahlentherapie von Hirnmetastasen des Mamma- und Bronchialkarzinomas

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    Hergarten, A.

    1987-01-13

    A total of 96 patients showing cerebral metastases were evaluated, who had been treated at any time during the period between 1971 and 1984. The mean interval from the point of time when the primary tumour was diagnosed to the first appearance of metastases in the brain was determined to be 20 months for mammary carcinomas and 0.8 months for bronchial carcinomas. As a rule, telecobalt 60 rays were used; the area of radiation was chosen so as to cover the total cranium and included two opposite lateral fields, the therapeutic programme and area of treatment being determined in each case on an individual basis. Generally, a total dose of 30 Gy was given under the protection of cortisone, split up into individual doses of 2 Gy administered 4-5 times weekly. The success of therapy thus achieved was judged from changes in neuological parameters. It was found that 50% of the patients showed considerable improvement. In view of an average survival time of 7.5 months it may be stated that the chances of survival for patients with mammary carcinomas receiving radiotherapy were considerably better than would have been assumed on the basis of data from relevant literature. In bronchial carcinomas radiotherapy is beneficial in that the symptoms are relieved, even though the mean survival time still is only 3.8 months.

  6. Uptake of technetium-99m methylene diphosphonate by fractured and osteoporotic bone after a pulse dose of Vitamin D/sub 3/. [Rats

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    Carr, E.A. Jr.; Carroll, M.; Montes, M.; Zielezny, M.

    1985-04-01

    The effect of a pulse dose of Vitamin D/sub 3/ on uptake of (/sup 99m/Tc)MDP by fractured and osteoporotic bone, respectively, was compared with D/sub 3/'s effect on uptake by normal bone in rats. At 4, 7, and 14 days, respectively, after femoral fracture, basal uptake was significantly increased at the fracture site by 336.8, 276.1, and 183.5%, respectively, over the contralateral control site. D/sub 3/-treated rats had lower uptakes than untreated controls at all three fracture sites and at 12 of 15 normal bone sites but analysis of variance showed the uptake differences were not significant. Cortisone-induced osteoporosis caused a significant decrease in basal uptake. The decrease occurred in all nine bone areas studied. D/sub 3/ caused a significant increase in uptake by these osteoporotic bones, but a significant decrease in uptake by the same bones in normal controls. Thus, D/sub 3/ had an effect on uptake by the bone lesion, osteoporosis, that differed from D/sub 3/'s effect on uptake by fracture or normal bone.

  7. Tc-99m MDP bone clearance - a new technique designed to evaluate bone metabolism on a quantitative basis. Tc-99m-MDP Knochenclearance, ein neues Verfahren zur quantitativen Beurteilung des Knochenstoffwechsels

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    Fegert, J.

    1984-09-18

    A new technique for the quantitative evaluation of bone metabolism (bone clearance) is described, the diagnostic value of which at the hospital level is rated higher than that of qualitative bone scanning, as it permits metabolic imbalances in the bone to be ascertained at an earlier stage and to reduce the radiation exposure of the patients and hospital staff. Bone clearance was expressed as the ratio between the per minute accumulation of activity in the bone and the plasma activity per ml and calculated on the basis of the measured elimination rate of 99m-Tc MDP from the blood and soft tissues. The latter, in turn, was determined by subtraction of the glomerular filtration rate from the wholebody retention of 113mIn DTPA. The results obtained were corrected for the relative amounts of radioactivity bound to plasma proteins. Considerably increased clearance values were determined for patients showing metabolic or systemic disorders and, in particular, thyrotoxicosis (normal thyroid findings in the scintigrams) as well as in cases of premature ossification of epiphyseal cartilages in a growing organism. Markedly decreased clearance values were seen in patients receiving cortisone. The measured values were easily reproducible and consistent with the relevant hormone levels, while being completely independent of the renal function. (TRV).

  8. Class-Specific Histone Deacetylase Inhibitors Promote 11-Beta Hydroxysteroid Dehydrogenase Type 2 Expression in JEG-3 Cells

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    Katie L. Togher

    2017-01-01

    Full Text Available Exposure to maternal cortisol plays a crucial role in fetal organogenesis. However, fetal overexposure to cortisol has been linked to a range of short- and long-term adverse outcomes. Normally, this is prevented by the expression of an enzyme in the placenta called 11-beta hydroxysteroid dehydrogenase type 2 (11β-HSD2 which converts active cortisol to its inactive metabolite cortisone. Placental 11β-HSD2 is known to be reduced in a number of adverse pregnancy complications, possibly through an epigenetic mechanism. As a result, a number of pan-HDAC inhibitors have been examined for their ability to promote 11β-HSD2 expression. However, it is not known if the effects of pan-HDAC inhibition are a general phenomenon or if the effects are dependent upon a specific class of HDACs. Here, we examined the ability of pan- and class-specific HDAC inhibitors to regulate 11β-HSD2 expression in JEG3 cells. We find that pan-, class I, or class IIa HDAC inhibition promoted 11β-HSD2 expression and prevented cortisol or interleukin-1β-induced decrease in its expression. These results demonstrate that targeting a specific class of HDACs can promote 11β-HSD2 expression in JEG3 cells. This adds to the growing body of evidence suggesting that HDACs may be crucial in maintaining normal fetal development.

  9. Structure and Catalytic Mechanism of Human Steroid 5-Reductase (AKR1D1)

    Energy Technology Data Exchange (ETDEWEB)

    Costanzo, L.; Drury, J; Christianson, D; Penning, T

    2009-01-01

    Human steroid 5{beta}-reductase (aldo-keto reductase (AKR) 1D1) catalyzes reduction of {Delta}{sup 4}-ene double bonds in steroid hormones and bile acid precursors. We have reported the structures of an AKR1D1-NADP{sup +} binary complex, and AKR1D1-NADP{sup +}-cortisone, AKR1D1-NADP{sup +}-progesterone and AKR1D1-NADP{sup +}-testosterone ternary complexes at high resolutions. Recently, structures of AKR1D1-NADP{sup +}-5{beta}-dihydroprogesterone complexes showed that the product is bound unproductively. Two quite different mechanisms of steroid double bond reduction have since been proposed. However, site-directed mutagenesis supports only one mechanism. In this mechanism, the 4-pro-R hydride is transferred from the re-face of the nicotinamide ring to C5 of the steroid substrate. E120, a unique substitution in the AKR catalytic tetrad, permits a deeper penetration of the steroid substrate into the active site to promote optimal reactant positioning. It participates with Y58 to create a 'superacidic' oxyanion hole for polarization of the C3 ketone. A role for K87 in the proton relay proposed using the AKR1D1-NADP{sup +}-5{beta}-dihydroprogesterone structure is not supported.

  10. Clinical, socio-demographic and radiological predictors of short-term outcome in rotator cuff disease

    Directory of Open Access Journals (Sweden)

    Engebretsen Kaia

    2010-10-01

    Full Text Available Abstract Background Shoulder pain is common with rotator cuff disease as the most frequently used clinical diagnosis. There is a wide range of treatment options for this condition, but limited evidence to guide patients and clinicians in the choice of treatment strategy. The purpose of this study was to investigate possible prognostic factors of short-term outcome after corticosteroid injection for rotator cuff disease. Methods We performed analyses of data from 104 patients who had participated in a randomized controlled study. Socio-demographic, clinical and radiographic baseline factors were assessed for association with outcome at six-weeks follow-up evaluated by Shoulder Pain and Disability Index (SPADI and patient perceived outcome. Factors with significant univariate association were entered into multivariate linear and logistic regression analyses. Results In the multivariate analyses; a high SPADI score indicating pain and disability at follow-up was associated with decreasing age, male gender, high baseline pain and disability, being on sick-leave, and using regular pain medication. A successful patient perceived outcome was associated with not being on sick-leave, high active abduction, local corticosteroid injection and previous cortisone injections. Structural findings of rotator cuff tendon pathology on MRI and bursal exudation or thickening on ultrasonography did not contribute to the predictive model. Conclusions Baseline characteristics were associated with outcome after corticosteroid injection in rotator cuff disease. Sick-leave was the best predictor of poor short-term outcome. Trial registration: Clinical trials NCT00640575

  11. Radioiodine therapy in Graves` disease; Radioiodtherapie der Immunhyperthyreose

    Energy Technology Data Exchange (ETDEWEB)

    Schuemichen, C. [Rostock Univ., Zentrum fuer Radiologie, Klinik und Poliklinik fuer Nuklearmedizin (Germany)

    1997-12-01

    Analogous to subtotal struma resection, stable long-term results are attained with radioiodine therapy of immunohyperthyreosis only with an ablative therapy concept. Hypothyreosis is thus no longer an undesired or unavoidable side effect of radioiodine therapy, but constitutes part of the treatment principle. In addition to the negligible theoretical low late risk of radiation effect, an increase in immunostimulation is induced in the majority of patients by means of increased antigen presentation. In a minority of patients, this has detrimental effects on the treatment results and leads to a requirement for relatively high focal doses (200-300 Gy) to achieve a generally satisfactory therapeutic result. In individual cases, endocrine orbitopathy may be exacerbated or elicited. It is therefore recommended that radioiodine therapy of immunohyperthyreosis should be undertaken with cortisone protection as a matter of principle. (orig.) [Deutsch] In Analogie zur subtotalen Strumaresektion werden auch mit der Radioiodtherapie der Immunhyperthyreose nur mit einem ablativen Therapiekonzept stabile Langzeitergebnisse erzielt. Die Hypothyreose ist somit nicht laenger unerwuenschte oder unvermeidliche Nebenwirkung der Radioiodtherapie, sondern Bestandteil des Behandlungsprinzips. Neben dem vernachlaessigbar geringen theoretischen Spaetrisiko durch Strahleneinwirkung wird bei einem Grossteil der Patienten durch eine vermehrte Antigenpraesentation eine Zunahme der Immunstimulation induziert, die bei einem kleineren Teil der Patienten das Behandlungsergebnis beeintraechtigt und dazu fuehrt, dass relativ hohe Herddosen (200-300 Gy) fuer ein insgesamt zufriedenstellendes Behandlungsergebnis erforderlich werden. In Einzelfaellen kann hierdurch auch eine endokrine Orbitopathie verschlechtert oder neu ausgeloest werden. Es wird daher empfohlen, die Radioiodtherapie der Immunhyperthyreose grundsaetzlich unter Kortisonschutz vorzunehmen. (orig.)

  12. Corticosterone metabolites originating as a consequence of solvated electron (e(-)aq) emission.

    Science.gov (United States)

    Brenn, Eric; Mitulović, Goran; Quint, Ruth-Maria; Getoff, Nikola

    2014-01-01

    Corticosterone in water-ethanol solution can eject "solvated electrons" (eaq(-)) when excited into the singlet state by monochromatic UV-light (λ=254 nm). As a consequence of this process free radicals and H(+) ions were also generated. Hence, the objectives of this study were to determine the quantum yield, Q, at different corticosterone concentrations, and elucidate the fate of the generated free radicals and the involved reaction mechanisms. Because of the formation of associates, which consume a part of the emitted eaq(-), the Q decrease with increase of cortisone concentration. Additionally the H(+) ions scavenge and convert a part of the ejected eaq(-) into H-atoms. In comparsion with progesterone, the Q of corticosterone is much higher. Evidently, this effect is due to the two OH groups of corticosterone, which act as intense emission centres for eaq(-). Thereby, the generated free radicals from corticosterone lead to formation of metabolites, which were analyzed by combination of liquid-chromatography with mass spectrometry (LC/MS) method. Two of them were identified: 5α-pregnan-3α, 21-diol-11, 20-dione and 20β-dihydroxycortisone. Both have the same mass number of 348.230. To explain the involved, rather complicated processes, a probable reaction mechanism is suggested. Copyright © 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  13. [Detection of glucocorticoids by pressurized capillary electrochromatography with ultra-violet detection and its application in hair analysis].

    Science.gov (United States)

    Li, Boxiang; Zheng, Minmin; Lu, Lanxiang; Wu, Xiaoping

    2011-08-01

    An effective and convenient method for glucocorticoid analysis in hair by reversed-phase pressurized capillary electrochromatography (pCEC) with ultra-violet (UV) detection was developed. Eight glucocorticoids (betamethasone, dexamethasone, prednisone, prednisolone, prednisolone acetate, hydrocortisone acetate, cortisone acetate and corticosterone) were separated within 20 min in an isocratic mode pCEC. The separations were performed on a reversed-phase C18 column, and with 245 nm as the UV detection wavelength. The mobile phase was composed of 1.5 mmol/L Tris buffer (pH 8.0) and acetonitrile (65: 35, v/v), at a pump flow rate of 0.105 mL/min. All of the compounds showed good linearity in the range of 0.036 - 4.0 mmol/L. The limits of detection (LODs) for all glucocorticoids were of microg/g levels. The proposed method was applied to the analysis of hair samples. The interference of hair matrices was effectively eliminated by protein enzymatic digestion, followed by a methanol extraction and a solid phase extraction (SPE) clean up step. The average recoveries of 71% - 85% at different fortified levels of glucocorticoids were achieved. This non-invasive method is useful for rapidly estimating the level of drug exposure in drug chronic abuse and monitoring the compliance of therapeutic drugs.

  14. Methods for in vitro percutaneous absorption studies V: Permeation through damaged skin.

    Science.gov (United States)

    Bronaugh, R L; Stewart, R F

    1985-10-01

    The permeation of compounds through skin damaged by different methods was compared because agents that are absorbed through skin are sometimes applied to a damaged barrier. The removal of the stratum corneum by stripping the skin with cellophane tape was the most effective method for enhancing absorption. A minimal increase in water permeation was obtained when one abrasion line was made with a hypodermic needle, but the absorption increased substantially when three to six lines were made across the site of application. Similar values were obtained with in vivo and in vitro techniques for penetration of cortisone and nicotinic acid through normal and abraded rat skin. Sever damage by UV irradiation to rats in vivo resulted in nicotinic acid absorption similar to that obtained in vitro through abraded or tape-stripped skin. Damage from mild irradiation could not be accurately duplicated by in vitro methods. The magnitude of the increase in absorption of seven chemicals through abraded human and rat skin was related to the extent to which the molecules were absorbed by the skin. The greatest increases in penetration were obtained with the compounds that were most poorly absorbed.

  15. Determination of endocrine disrupting compounds using temperature-dependent inclusion chromatography: I. Optimization of separation protocol.

    Science.gov (United States)

    Zarzycki, Paweł K; Włodarczyk, Elzbieta; Baran, Michał J

    2009-10-30

    In the present work we optimised the separation of battery of key UV non-transparent low-molecular-mass compounds having possible endocrine disrupting compounds (EDCs) activity or which may be used as the endocrine effect biomarkers. Simple optimization strategy was based on strong temperature effect that is driven by electrostatic interactions between macrocyclic mobile phase additives like cyclodextrins and eluted components of interest under C18 stationary phase and acetonitrile/water mobile phase conditions. Particularly, the effect of temperature involving native beta-cyclodextrin and its hydroxypropyl derivative to improve separation of number of natural (d-equilenin, equilin, estetrol, estriol, estrone, 17beta-estradiol, 17alpha-hydroxyprogesterone, 20alpha-hydroxyprogesterone, cortisol, cortisone, progesterone, testosterone, tetrahydrocortisol and tetrahydrocortisone) and artificial steroids (ethynylestradiol, norgestrel isomers, medroxyprogesterone, mestranol, methyltestosterone, norethindrone, 17alpha-estradiol) as well as non-steroidal compounds (diethylstilbesterol, bisphenol A, 4-tert-butylphenol, dimethyl phthalate, dibutyl phthalate and dioctyl phthalate) was investigated. It has been found that successful isocratic separation of 27 chemicals can be achieved using acetonitrile/water eluents modified with beta-cyclodextrin or hydroxypropyl-beta-cyclodextrin at concentration of 10 mM and temperature of 47 degrees C. Separation protocol is simple, reliable, direct and non-radioactive and may be easily adapted for rapid separation and quantification of wide range of given steroids and related EDCs in environmental samples, particularly those that are characterised by unstable biological matrix and components of interest load.

  16. Ultraviolet exposure of thymocytes: selective inhibition of apoptosis.

    Science.gov (United States)

    Ojeda, F; Guarda, M I; Lovengreen, C; Hidalgo, M A; Folch, H; Härtel, S; Maldonado, C

    2004-06-01

    To evaluate selective effects of ultraviolet (UV) irradiation on spontaneous and induced apoptosis in freshly extracted mice thymocytes. Cells were exposed to UV radiation with emission peaks of 365 nm (UVA) exposures of 1620-10200 J m(-2), of 312 nm (UVB) exposures of 34-1620 J m(-2) or of 254 nm (UVC) exposures of 1.5-1620 J m(-2), and incubated for 5.5 h with or without hydrocortisone, phorbol-12-myristate-13-acetate or anti-Fas antibody. Additionally, cells were irradiated with gamma-rays (5 Gy) before UVB exposure (408 J m(-2)) at different times. Apoptosis was quantified by DNA fragmentation. Up to an irradiation of 5000 J m(-2), UVA exposure did not show any effect on thymocyte apoptosis, while at 10200 J m(-2) irradiation, considerable DNA fragmentation was observed. In contrast, UVB and UVC irradiation clearly inhibited natural and cortisone-induced apoptosis. Moreover, UVB inhibited apoptosis triggered by phorbol-12-myristate-13-acetate and gamma-irradiation, but not by anti-Fas antibody. The response of mouse thymocytes in culture to UV irradiation strongly depends on the wavelength used. It is suggested that either a survival or an apoptotic pathway occurs depending on the physiological state of the cell, spectral composition of the UV light and cell type. The possible involvement of extracellular signal-regulated kinase and stress-activated protein kinase/c-Jun N-terminal kinase in the apoptotic pathway is discussed.

  17. Changes of several adrenal delta 4-steroids measured by HPLC-UV spectrometry in neonatal patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

    Science.gov (United States)

    Saisho, S; Shimozawa, K; Yata, J

    1990-01-01

    We have developed an easy and rapid method of reverse-phase high-performance liquid chromatography (HPLC)-UV spectrometry for measuring adrenal delta 4-steroids. Three female neonates with adrenal 21-hydroxylase deficiency (2 salt-losers and 1 simple virilizer), two of whom were recalled by neonatal mass-screening for congenital adrenal hyperplasia (CAH), were diagnosed using this method. Changes of several adrenal steroids were examined in these patients before and after treatment with hydrocortisone. Before treatment, the cortisone and cortisol peaks were very low and those of 17 alpha-hydroxyprogesterone (17-OHP) and 21-deoxycortisol (21-DOF) were high in all 3 patients (17-OHP: 79.9-997 nmol/l, 21-DOF: 83.7-324 nmol/l). The androstenedione peak was also high in 2 of them. A peak produced by 21-deoxycortisone, which is a product of oxidation of 21-DOF at the C-11 position, was also detected in all cases (14.5-297 nmol/l). After treatment, all of these abnormally elevated delta 4-steroids decreased or disappeared. This new method is thought to be valuable for the rapid diagnosis of CAH, and especially for use in neonatal mass-screening for CAH.

  18. Chronic inhibition of 11 β -hydroxysteroid dehydrogenase type 1 activity decreases hypertension, insulin resistance, and hypertriglyceridemia in metabolic syndrome.

    Science.gov (United States)

    Schnackenberg, Christine G; Costell, Melissa H; Krosky, Daniel J; Cui, Jianqi; Wu, Charlene W; Hong, Victor S; Harpel, Mark R; Willette, Robert N; Yue, Tian-Li

    2013-01-01

    Metabolic syndrome is a constellation of risk factors including hypertension, dyslipidemia, insulin resistance, and obesity that promote the development of cardiovascular disease. Metabolic syndrome has been associated with changes in the secretion or metabolism of glucocorticoids, which have important functions in adipose, liver, kidney, and vasculature. Tissue concentrations of the active glucocorticoid cortisol are controlled by the conversion of cortisone to cortisol by 11 β -hydroxysteroid dehydrogenase type 1 (11 β -HSD1). Because of the various cardiovascular and metabolic activities of glucocorticoids, we tested the hypothesis that 11 β -HSD1 is a common mechanism in the hypertension, dyslipidemia, and insulin resistance in metabolic syndrome. In obese and lean SHR/NDmcr-cp (SHR-cp), cardiovascular, metabolic, and renal functions were measured before and during four weeks of administration of vehicle or compound 11 (10 mg/kg/d), a selective inhibitor of 11 β -HSD1. Compound 11 significantly decreased 11 β -HSD1 activity in adipose tissue and liver of SHR-cp. In obese SHR-cp, compound 11 significantly decreased mean arterial pressure, glucose intolerance, insulin resistance, hypertriglyceridemia, and plasma renin activity with no effect on heart rate, body weight gain, or microalbuminuria. These results suggest that 11 β -HSD1 activity in liver and adipose tissue is a common mediator of hypertension, hypertriglyceridemia, glucose intolerance, and insulin resistance in metabolic syndrome.

  19. Chronic Inhibition of 11β-Hydroxysteroid Dehydrogenase Type 1 Activity Decreases Hypertension, Insulin Resistance, and Hypertriglyceridemia in Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    Christine G. Schnackenberg

    2013-01-01

    Full Text Available Metabolic syndrome is a constellation of risk factors including hypertension, dyslipidemia, insulin resistance, and obesity that promote the development of cardiovascular disease. Metabolic syndrome has been associated with changes in the secretion or metabolism of glucocorticoids, which have important functions in adipose, liver, kidney, and vasculature. Tissue concentrations of the active glucocorticoid cortisol are controlled by the conversion of cortisone to cortisol by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1. Because of the various cardiovascular and metabolic activities of glucocorticoids, we tested the hypothesis that 11β-HSD1 is a common mechanism in the hypertension, dyslipidemia, and insulin resistance in metabolic syndrome. In obese and lean SHR/NDmcr-cp (SHR-cp, cardiovascular, metabolic, and renal functions were measured before and during four weeks of administration of vehicle or compound 11 (10 mg/kg/d, a selective inhibitor of 11β-HSD1. Compound 11 significantly decreased 11β-HSD1 activity in adipose tissue and liver of SHR-cp. In obese SHR-cp, compound 11 significantly decreased mean arterial pressure, glucose intolerance, insulin resistance, hypertriglyceridemia, and plasma renin activity with no effect on heart rate, body weight gain, or microalbuminuria. These results suggest that 11β-HSD1 activity in liver and adipose tissue is a common mediator of hypertension, hypertriglyceridemia, glucose intolerance, and insulin resistance in metabolic syndrome.

  20. [Correlations between the hypothalamo-pituitary-adrenal axis and the metabolic syndrome].

    Science.gov (United States)

    Góth, Miklós; Hubina, Erika; Korbonits, Márta

    2005-01-09

    The metabolic syndrome has several similarities with Cushing's syndrome (impaired glucose tolerance, hypertension, dyslipidemia, central obesity) suggesting that abnormalities in the regulation of the hypothalamic-pituitary-adrenal axis may have a link with the metabolic syndrome. Several studies suggested an association between the clinical signs of the metabolic syndrome and the increased hypothalamic-pituitary-adrenal axis activity based on increased cortisol concentration at 09.00 a.m. and increased cortisol response to corticotropin. According to the Barker hypothesis the fetal malnutrition could determine adult cardiovascular diseases (coronary heart disease, hypertension), some endocrine and metabolic disorders (obesity, type 2 diabetes and hyperlipidemia). The suggested mechanism of the phenomenon is that the suboptimal fetal nutrition results in glucocorticoid overproduction. The 11beta-hydroxysteroid dehydrogenase (converts biological inactive cortisone to cortisol and vice versa) is an important enzyme in cortisol metabolism. The increased expression of 11beta-hydroxysteroid dehydrogenase type 1 in fat tissue could lead to central obesity and impaired glucose tolerance. The hypothesis that increased corticotropin-releasing hormone production drives the overactive hypothalamo-pituitary-adrenal axis was not proven. Further investigations are needed to identify additional pathogenetic factors and to find new therapeutic possibilities.

  1. Comparison of a homology model and the crystallographic structure of human 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) in a structure-based identification of inhibitors

    Science.gov (United States)

    Miguet, Laurence; Zhang, Ziding; Barbier, Maryse; Grigorov, Martin G.

    2006-02-01

    Human 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) catalyzes the interconversion of cortisone into active cortisol. 11βHSD1 inhibition is a tempting target for the treatment of a host of human disorders that might benefit from blockade of glucocorticoid action, such as obesity, metabolic syndrome, and diabetes type 2. Here, we report an in silico screening study aimed at identifying new selective inhibitors of human 11βHSD1 enzyme. In the first step, homology modeling was employed to build the 3D structure of 11βHSD1. Further, molecular docking was used to validate the predicted model by showing that it was able to discriminate between known 11βHSD1 inhibitors or substrates and non-inhibitors. The homology model was found to reproduce closely the crystal structure that became publicly available in the final stages of this work. Finally, we carried out structure-based virtual screening experiments on both the homology model and the crystallographic structure with a database of 114'000 natural molecules. Among these, 15 molecules were consistently selected as inhibitors based on both the model and crystal structures of the enzyme, implying a good quality for the homology model. Among these putative 11βHSD1 inhibitors, two were flavonone derivatives that have already been shown to be potent inhibitors of the enzyme.

  2. Patterns of endogenous steroids in apathetic refugee children are compatible with long-term stress

    Directory of Open Access Journals (Sweden)

    Söndergaard Hans

    2012-06-01

    Full Text Available Abstract Background During the last few years, a number of children of asylum applicants in Sweden developed an apathetic or unconscious state. The syndrome was perceived as new, and various explanations were advanced such as factitious disorder, intoxication, or stress. Considering a potential association between traumatic stress and regulation of steroids biosynthesis, this study explored whether changes in concentrations of endogenous steroids were associated with the above syndrome. Methods Eleven children were recruited in the study. Concentrations of steroids in blood samples were determined using high sensitivity liquid chromatography tandem mass spectrometry methods. Symptoms were assessed with a clinical rating scale developed for the study. Steroid concentrations were measured at the entry into study and after recovery; and concentrations were evaluated for the association with the symptoms in apathetic children. Results Cortisol and cortisone concentrations at baseline were negatively associated with duration of the symptoms from entry into the study to clinical recovery. Higher concentrations of pregnanes (pregnenolone, 17-OH-pregnenolone, and dehydroepiandrosterone were observed in the symptomatic state and the concentrations decreased after the recovery. Conclusions Pattern of low cortisol concentrations found in apathetic children is consistent with long-term stress. An increase of upstream steroid metabolites (pregnanes was found to be associated with the symptomatic state.

  3. KPC-producing Klebsiella pneumoniae enteric colonization acquired during intensive care unit stay: the significance of risk factors for its development and its impact on mortality.

    Science.gov (United States)

    Papadimitriou-Olivgeris, Matthaios; Marangos, Markos; Fligou, Fotini; Christofidou, Myrto; Sklavou, Christina; Vamvakopoulou, Sophia; Anastassiou, Evangelos D; Filos, Kriton S

    2013-10-01

    A prospective observational study of 226 intensive care unit (ICU) patients was conducted during a 25-month period. Rectal samples were taken at day 1, 4, and 7 and, afterwards, once weekly. Klebsiella pneumoniae was identified using standard techniques, whereas the presence of bla(KPC) gene was confirmed by PCR. During ICU stay, 72.6% of the patients were colonized with Klebsiella pneumoniae carbapenemases (KPC)-producing K. pneumoniae (KPC-Kp). Male gender, prior bed occupants, and patients in nearby beds colonized with KPC-Kp, tracheotomy, number of invasive catheters inserted, and number of antibiotics administered were the major risk factors for KPC-Kp colonization. ICU mortality (35.4%) was significantly related to Simplified Acute Physiology II score and respiratory insufficiency upon admission, cortisone administration, aminoglycoside administration, confirmed KPC-Kp infection, and severe sepsis or septic shock. The high prevalence of KPC-Kp enteric carriage in ICU patients and the significant mortality associated with KPC-Kp infection dictate the importance of early identification and isolation of such carriers.

  4. Symmetry adapted cluster-configuration interaction calculation of the photoelectron spectra of famous biological active steroids

    Science.gov (United States)

    Abyar, Fatemeh; Farrokhpour, Hossein

    2014-11-01

    The photoelectron spectra of some famous steroids, important in biology, were calculated in the gas phase. The selected steroids were 5α-androstane-3,11,17-trione, 4-androstane-3,11,17-trione, cortisol, cortisone, corticosterone, dexamethasone, estradiol and cholesterol. The calculations were performed employing symmetry-adapted cluster/configuration interaction (SAC-CI) method using the 6-311++G(2df,pd) basis set. The population ratios of conformers of each steroid were calculated and used for simulating the photoelectron spectrum of steroid. It was found that more than one conformer contribute to the photoelectron spectra of some steroids. To confirm the calculated photoelectron spectra, they compared with their corresponding experimental spectra. There were no experimental gas phase Hesbnd I photoelectron spectra for some of the steroids of this work in the literature and their calculated spectra can show a part of intrinsic characteristics of this molecules in the gas phase. The canonical molecular orbitals involved in the ionization of each steroid were calculated at the HF/6-311++g(d,p) level of theory. The spectral bands of each steroid were assigned by natural bonding orbital (NBO) calculations. Knowing the electronic structures of steroids helps us to understand their biological activities and find which sites of steroid become active when a modification is performing under a biological pathway.

  5. Radiotherapy for maxillo-facial hemangiomas in children. Dental and periodontal long term effects.

    Science.gov (United States)

    Colella, G; Vuolo, G; Siniscalchi, G; Moscariello, A; Itro, A

    2005-09-01

    Vascular maxillo-facial malformations, common pathologies in children, represent 7% of all benign tumors. They are divided into vascular malformations and hemangiomas. In the 70s-80s radiotherapy was the most applied technique, but because of its misuse or overdose, it could lead to relevant and hard consequences for the impact on the salivar glands, periodontium and growing maxillo-facial nuclei. The authors describe the case of a 38-year-old man, who, during infancy, was submitted to radiotherapy for a hemangioma to his chin and cheek. He was under observation for an agressive periodontitis, followed by a serious facial asimmetry, located in his irradiated side. They describe the therapy and the results obtained, underlying the particular difficulties detected in operating on tissues hardly and often irreversibly injured by radiotherapy. On the basis of this clinical case and of the most up-dated knowledge, therapeutical alternatives such as embolization, cryotherapy, cortisonic systemic and intralesional therapy, the use of interferon gamma 2 and the use of the most recent laser, are analyzed, and advantages and disadvantages and the most appropriate indications are underlined.

  6. Current practice of glucocorticoid replacement therapy and patient-perceived health outcomes in adrenal insufficiency - a worldwide patient survey

    Directory of Open Access Journals (Sweden)

    Forss M

    2012-06-01

    Full Text Available Abstract Background The aim was to survey current practice in glucocorticoid replacement therapy and self-perceived health outcomes in patients with adrenal insufficiency. Methods Participants were recruited via patient organizations to respond anonymously to a web-based survey developed by clinical experts. Unique entries were set up for each patient organization enabling geographical localization of the entries. Results 1245 participants responded (primary adrenal insufficiency: 84%; secondary adrenal insufficiency: 11%; unsure: 5%. Therapies included hydrocortisone (75%, prednisone/prednisolone (11%, cortisone acetate (6% and dexamethasone (4%. Dosing regimens were once daily (10%, twice daily (42%, thrice daily (32% or other (17%. Compromised subjective health necessitating changes to physical activity or social-, work- or family life was reported by 64% of the participants. 40% of the participants reported absence from work/school in the last 3 months. Irrespective of diagnosis, 76% were concerned about long-term side-effects of therapy, mainly osteoporosis (78%, obesity (64% and cardiovascular morbidity (46%. 38% of the participants had been hospitalized in the last year. Conclusions Glucocorticoid replacement therapy among the respondents consisted primarily of hydrocortisone administered twice or thrice daily. A majority reported impact of their disease or treatment on subjective health requiring alterations in e.g. physical activity or family life. Three quarters reported concerns about long-term side-effects of the treatment. These data demonstrate - from the patients' perspective - a need for improvement in the management of adrenal insufficiency.

  7. Decreased physical activity, reduced QoL and presence of debilitating fatigue in patients with Addison's disease.

    Science.gov (United States)

    van der Valk, Eline S; Smans, Lisanne C C J; Hofstetter, Hedwig; Stubbe, Janine H; de Vries, Marieke; Backx, Frank J G; Hermus, Ad R M M; Zelissen, Pierre M J

    2016-09-01

    Health-related quality of life in patients with Addison's disease has been assessed in various European countries, indicating a reduced quality of life. However, no studies have addressed the impact of Addison's disease on physical activity. The aim of this study was to investigate the quality of life in Dutch patients with Addison's disease particularly regarding the presence of fatigue and the ability to be physically active. In this cross-sectional study, a postal survey was performed among Dutch patients with Addison's disease on stable glucocorticoid replacement therapy with hydrocortisone or cortisone acetate. For quality of life and physical activity assessment, patients completed general and health-related quality of life and physical activity questionnaires, and scores were compared to Dutch controls. A total of 328 patients with Addison's disease were studied. In patients with Addison's disease, only 45·7% met the standard of physical activity (Combinorm) compared to 67·8% of Dutch controls (P Addison's disease, combined with a reduced subjective health-related QoL and increased fatigue. © 2016 John Wiley & Sons Ltd.

  8. Aplastic anemia as a feature of systemic lupus erythematosus: a case report and literature review.

    Science.gov (United States)

    Chalayer, Émilie; Ffrench, Martine; Cathébras, Pascal

    2015-06-01

    Peripheral cytopenias are common in systemic lupus erythematosus, but bone marrow involvement is rarely reported. Aplastic anemia is the result of immune-mediated destruction of hematopoietic stem cells causing pancytopenia and characterized by an empty bone marrow. This rare but serious disease has been described as an unusual manifestation of systemic lupus erythematosus. We reviewed the 25 cases published in the English language literature and discuss the clinical presentation, outcome, treatment, and pathophysiology of aplastic anemia as a complication of systemic lupus erythematosus. We report here the first case of aplastic anemia associated with systemic lupus erythematosus treated with an allogeneic hematopoietic stem cell transplant. Over one half of patients received concomitantly the diagnoses of systemic lupus erythematosus and aplastic anemia. No clinical or histological features can distinguish primary aplastic anemia from aplastic anemia occurring in systemic lupus erythematosus patients. The overall mortality is about 15% and corticosteroid-based therapy alone or in combination with other immunomodulatory drugs can restore bone marrow function. Systemic lupus erythematosus may be complicated by bone marrow involvement. The diagnosis of peripheral cytopenias should be confirmed by bone marrow aspiration. All these patients should receive cortisone as a first treatment. Plasma exchanges seem to have some efficacy. Other different immunomodulatory therapies were used with variable results.

  9. Bone formation induced in mouse thigh by cultured human cells.

    Science.gov (United States)

    Anderson, H C; Coulter, P R

    1967-04-01

    Cultured FL human amnion cells injected intramuscularly into cortisone-conditioned mice proliferate to form discrete nodules which become surrounded by fibroblasts. Within 12 days, fibroblastic zones differentiate into cartilage which calcifies to form bone. Experiments were conducted to test the hypothesis that FL cells behave as an inductor of bone formation. In the electron microscope, FL cells were readily distinguished from surrounding fibroblasts. Transitional forms between the two cell types were not recognized. Stains for acid mucopolysaccharides emphasized the sharp boundary between metachromatic fibroblastic and cartilaginous zones and nonmetachromatic FL cells. (35)S was taken up preferentially by fibroblasts and chondrocytes and then deposited extracellularly in a manner suggesting active secretion of sulfated mucopolysaccharides. FL cells showed negligible (35)S utilization and secretion. FL cells, labeled in vitro with thymidine-(3)H, were injected and followed radioautographically, during bone formation. Nuclear label of injected FL cells did not appear in adjacent fibroblasts in quantities sufficient to indicate origin of the latter from FL cells. The minimal fibroblast nuclear labeling seen may represent reutilization of label from necrotic FL cells. It is suggested that FL cells injected into the mouse thigh induced cartilage and bone formation by host fibroblasts.

  10. [Salter innominate osteotomy for the treatment of developmental dysplasia of the hip: 37 years of follow-up].

    Science.gov (United States)

    Atik, O Şahap; Daldal, İsmail

    2015-01-01

    In this article, we report the radiological and clinical status at postoperative 37th year of a 39-year-old male patient who was treated with bilateral Salter innominate osteotomy due to bilateral developmental dysplasia of the hip when he was two years old. The patient expressed that he had no complaint including pain or limitation in range of motion in both hip joints for 37 years. Pain started six months ago in right hip joint. Patient used cortisone for 12 months with a diagnosis of Henoch-Schönlein purpura five years ago. Radiologic imaging revealed findings of bilateral Salter innominate osteotomy and avascular osteonecrosis on the right femoral head. Kirschner wires which were used during operations 37 years ago remained buried in pelvic bone. Bilateral development of acetabulum and femoral head was very good. Anteroposterior and lateral radiographs of right hip joint revealed degenerative osteoarthritis secondary to avascular osteonecrosis on the right femoral head. Except for the last six months, patient has been living without pain or limitation in range of motion for postoperative 37 years.

  11. Wars in the history of rheumatology

    Directory of Open Access Journals (Sweden)

    P. Marson

    2011-09-01

    Full Text Available Some important discoveries in the history of rheumatology happened during war periods. It is well known that arthritis associated with conjunctivitis and urethritis, following dysenteric episodes, has been described during the First World War from the German Hans Reiter and, nearly contemporarily, from the French Nöel Fiessinger and Edgar Leroy. Less known is instead the fact that the first cases of sympathetic algoneurodystrophy have been reported by the American Silas Weir Mitchell in soldiers wounded by fire-arms, during the Civil War of Secession. Other war episodes have been crucial for the development of some drugs now abundantly applied to the care of rheumatic diseases. The discovery of therapeutic effects of immunosuppressive agents, in fact, happened as an indirect consequence of the use of poison gas, already during the First World War (mustard gas, but above all after an episode in the port of Bari in 1943, where an American cargo boat was sunk. It had been loaded with a quantity of cylinders containing a nitrogenous mustard, whose diffusion in the environment provoked more than 80 deaths owing to bone marrow aplasia.Moreover, the history of the cortisone shows a strict link to the Second World War, when Germany imported large quantities of bovine adrenal glands from Argentina, with the purpose of producing some gland extracts for the Luftwasse aviators, in order to increase their performance ability.

  12. 11-Beta hydroxysteroid dehydrogenase type 2 expression in white adipose tissue is strongly correlated with adiposity.

    Science.gov (United States)

    Milagro, Fermin I; Campión, Javier; Martínez, J Alfredo

    2007-04-01

    Glucocorticoid action within the cells is regulated by the levels of glucocorticoid receptor (GR) expression and two enzymes, 11-beta hydroxysteroid dehydrogenase type 1 (11betaHSD1), which converts inactive to active glucocorticoids, and 11-beta hydroxysteroid dehydrogenase type 2 (11betaHSD2), which regulates the access of active glucocorticoids to the receptor by converting cortisol/corticosterone to the glucocorticoid-inactive form cortisone/dehydrocorticosterone. Male Wistar rats developed obesity by being fed a high-fat diet for 56 days, and GR, 11betaHSD1 and 11betaHSD2 gene expression were compared with control-diet fed animals. Gene expression analysis of 11betaHSD1, 11betaHSD2 and GR were performed by RT-PCR in subcutaneous and retroperitoneal adipose tissue. High-fat fed animals overexpressed 11betaHSD2 in subcutaneous but not in retroperitoneal fat. Interestingly, mRNA levels strongly correlated in both tissues with different parameters related to obesity, such as body weight, adiposity and insulin resistance, suggesting that this gene is a reliable marker of adiposity in this rat model of obesity. Thus, 11betaHSD2 is expressed in adipose tissue by both adipocytes and stromal-vascular cells, which suggests that this enzyme may play an important role in preventing fat accumulation in adipose tissue.

  13. Stress, memory, and the hippocampus.

    Science.gov (United States)

    Wingenfeld, Katja; Wolf, Oliver T

    2014-01-01

    Stress hormones, i.e. cortisol in human and cortisone in rodents, influence a wide range of cognitive functions, including hippocampus-based declarative memory performance. Cortisol enhances memory consolidation, but impairs memory retrieval. In this context glucocorticoid receptor sensitivity and hippocampal integrity play an important role. This review integrates findings on the relationships between the hypothalamus-pituitary-adrenal (HPA) axis, one of the main coordinators of the stress response, hippocampus, and memory. Findings obtained in healthy participants will be compared with selected mental disorders, including major depressive disorder (MDD), posttraumatic stress disorder (PTSD), and borderline personality disorder (BPD). These disorders are characterized by alterations of the HPA axis and hippocampal dysfunctions. Interestingly, the acute effects of stress hormones on memory in psychiatric patients are different from those found in healthy humans. While cortisol administration has failed to affect memory retrieval in patients with MDD, patients with PTSD and BPD have been found to show enhanced rather than impaired memory retrieval after hydrocortisone. This indicates an altered sensitivity to stress hormones in these mental disorders.

  14. [Intra-articular injections].

    Science.gov (United States)

    Chapelle, Ch

    2015-09-01

    It is not unusual for a specialist or general practitioner to be presented with a pathology which necessitates the use of an intra-articular injection of corticosteroids, hyaluronic acid or a local anaesthetic. It would seem to be interesting to update and to precise the techniques and methods of intraarticular injections which have appeared in recent international publications, when we know that 30 % of the injections given into the knee and so called "dry" are incorrect and, therefore, inefficient. The indication of an articular injection depends, firstly, on the diagnosis which should be done with great care; after which should be an objective analysis complete with secondary effects linked to both the injection and the product used. The conditions of asepsis, the choice of needles and quantities of the injection and even the ways of the injections should be reviewed in detail. The last studies clearly question the secondary effects of the cartilage degradations of the cortisone given as an intra-articular injection and shows its efficiency on the pain and inflammatory phenomonen in osteoarthritis. Studies on hyaluronic acid are often contradictory going from a modest result to an important pain relief but it is necessary to be aware that the objective criteria are difficult to interpret. The use of local anaesthetics in intra-articular is limited by the few indications in view of the major risk of aggravating the pre-existing lesions by the disappearing signs of pain.

  15. Comparison between bioluminescence imaging technique and CFU count for the study of oropharyngeal candidiasis in mice.

    Science.gov (United States)

    Gabrielli, Elena; Roselletti, Elena; Luciano, Eugenio; Sabbatini, Samuele; Mosci, Paolo; Pericolini, Eva

    2015-05-01

    We recently described a bioluminescence in vivo imaging technique, representing a powerful tool to test the real-time progression of oropharyngeal candidiasis, hence potentially useful to evaluate the efficacy of antifungal therapies. In this study, the in vivo imaging technique was compared with CFU measurement of target organs (tongue, esophagus and stomach) for monitoring and quantifying oropharyngeal candidiasis. We have correlated these two analytical methods at different times post-infection using engineered, luminescent Candida albicans in mice rendered susceptible to oral candidiasis by cortisone-acetate. Scatter plots, Pearson correlation and Student's t test were used to compare the methods. We observed that the bioluminescence in vivo imaging technique was more reliable than CFU counts in detecting early infection of, and its extent in, the oral cavity of the mouse. This was also evident following the introduction of a variable such as treatment with fluconazole. The results described in this study could validate the bioluminescence in vivo imaging technique as a method to monitor and quantify oropharyngeal candidiasis and to assess early discovery of active compounds in vivo.

  16. Steroid control of steroidogenesis in isolated adrenocortical cells: molecular and species specificity.

    Science.gov (United States)

    Carsia, R V; Macdonald, G J; Malamed, S

    1983-06-01

    The molecular and species specificity of glucocorticoid suppression of corticosteroidogenesis was investigated in isolated adrenocortical cells. Trypsin-isolated cells from male rat, domestic fowl and bovine adrenal glands were incubated with or without steroidogenic agents and with or without steroids. Glucocorticoids were measured by radioimmunoassay or fluorometric assay after 1-2 h incubation. Glucocorticoids suppressed ACTH-induced steroidogenesis of isolated rat cells with the following relative potencies: corticosterone greater than cortisol = cortisone greater than dexamethasone. The mineralocorticoid, aldosterone did not affect steroidogenesis. Suppression by glucocorticoids was acute (within 1-2 h), and varied directly with the glucocorticoid concentration. Testosterone also suppressed ACTH-induced steroidogenesis. Glucocorticoid-type steroids have equivalent suppressive potencies, thus suggesting that these steroids may induce suppression at least partly by a common mechanism. Although corticosterone caused the greatest suppression, testosterone was more potent. The steroid specificity of suppression of cyclic AMP (cAMP)-induced and ACTH-induced steroidogenesis were similar, suggesting that suppression is not solely the result of interference with ACTH receptor function or the induction of adenylate cyclase activity. Exogenous glucocorticoids also suppressed ACTH-induced steroidogenesis of cells isolated from domestic fowl and beef adrenal glands, thus suggesting that this observed suppression may be a general mechanism of adrenocortical cell autoregulation.

  17. [Historical vision of shock].

    Science.gov (United States)

    Dosne Pasqualini, C

    1998-01-01

    The concept of shock and its close relationship with that of stress dates back to the experiments of Hans Selye initiated in 1936 at McGill University in Montreal, with whom I collaborated between 1939 and 1942. It was demonstrated that the General Adaptation Syndrome begins with an Alarm Reaction, which consists of a Stage of Shock and one of Counter-Shock, followed by a Stage of Adaptation and finally a Stage of Exhaustion. My Ph.D. thesis concluded that shock was due to an adrenal insufficiency postulating that active metabolic processes drain the body of certain essential compounds the lack of which causes shock. My interest in the role of the glucose metabolism in shock led me to work with Bernardo Houssay in 1942 at the Institute of Physiology of the University of Buenos Aires and in 1944 with C.N.H. Long at Yale University. There I developed a method for the induction of hemorrhagic shock in the guinea pig with 94% lethality; curiously, the administration of 200 mg of ascorbic acid prevented death. Upon my return to Buenos Aires, these results were confirmed and moreover, it was demonstrated that the administration of cortisone led to 40% survival of the animals while desoxycorticosterone had no effect. At the time, no explanation was available but to-day, half a century later, this Symposium should be able to explain the mechanisms leading to death by hemorrhagic shock.

  18. Optimization of dispersive liquid-phase microextraction based on solidified floating organic drop combined with high-performance liquid chromatography for the analysis of glucocorticoid residues in food.

    Science.gov (United States)

    Huang, Yuan; Zheng, Zhiqun; Huang, Liying; Yao, Hong; Wu, Xiao Shan; Li, Shaoguang; Lin, Dandan

    2017-05-10

    A rapid, simple, cost-effective dispersive liquid-phase microextraction based on solidified floating organic drop (SFOD-LPME) was developed in this study. Along with high-performance liquid chromatography, we used the developed approach to determine and enrich trace amounts of four glucocorticoids, namely, prednisone, betamethasone, dexamethasone, and cortisone acetate, in animal-derived food. We also investigated and optimized several important parameters that influenced the extraction efficiency of SFOD-LPME. These parameters include the extractant species, volumes of extraction and dispersant solvents, sodium chloride addition, sample pH, extraction time and temperature, and stirring rate. Under optimum experimental conditions, the calibration graph exhibited linearity over the range of 1.2-200.0ng/ml for the four analytes, with a reasonable linearity(r(2): 0.9990-0.9999). The enrichment factor was 142-276, and the detection limits was 0.39-0.46ng/ml (0.078-0.23μg/kg). This method was successfully applied to analyze actual food samples, and good spiked recoveries of over 81.5%-114.3% were obtained.

  19. Persistent hypokalemia after successful adrenalectomy in a patient with Cushing's syndrome due to ectopic ACTH secretion: possible role of 11beta-hydroxysteroid dehydrogenase inhibition.

    Science.gov (United States)

    Arteaga, E; Fardella, C; Campusano, C; Cárdenas, I; Martinez, P

    1999-12-01

    Ectopic ACTH secretion is characterized by a high incidence of hypokalemia. The pathophysiology of hypokalemia has not been totally clarified, although it has been postulated that excessive amounts of adrenal steroids may play a role, as well as a possible role of the inhibition of the enzyme 11beta-hydroxysteroid dehydrogenase (11beta-OHSD). This enzyme normally converts cortisol to cortisone avoiding the mineralocorticoid action of cortisol. We present a patient with ectopic ACTH secretion due to a metastatic carcinoid tumor. The clinical picture was characterized by maintained hypokalemia (1.4 mmol/l) resistant to potassium, spironolactone and ketoconazole administration. A bilateral adrenalectomy was performed but the hypokalemia persisted while he was receiving a physiological dose of cortisol. Eight days after adrenalectomy cortisol was replaced by an equivalent dose of dexamethasone. This change was followed by a rapid and persistent normalization of hypokalemia suggesting a mineralocorticoid effect of cortisol. In conclusion, the origin of hypokalemia in our patient with ectopic ACTH secretion was secondary to cortisol. We postulate that this peculiar effect of cortisol could have happened if an inhibition of 11beta-OHSD occurred.

  20. [Chondropathia patellae].

    Science.gov (United States)

    Mau, H

    1980-04-01

    Chondropathia patellae on a constitutional basis, in the narrow sense of the term, is predominantly responsible for producing the painful or irritated knee in juveniles and adolescents, with an incidence peak around the 20th year of life. The traumatic form associated with signs will often produce the same disorders of the patellar gliding path and of the gliding areas, such as the hyperpression and lateralisation syndrome, as well as habitual luxation. Clinically, degenerative articular damage may temporarily exacerbate into a kind of synovitis "chondsrodetritica", especially on overstraining and after microtraumas. On reviewing the case history, the retropatellar pain after prolonged seating and on walking downhill, is particularly characteristic; this pain can also radiate in medial direction. It is also often reported that the knee tends to "give way" suddenly, and to "interlock" or "become entangled". The leading clinical symptom is, besides a feeling of roughness, the "characteristic" pain caused by the gliding pressure of the patella. Conservative treatment, consisting of physiotherapy, isometric exercises of the quadriceps femoris muscle preceded or if permissible followed by heat and massage treatment, and therapy directed at protecting the cartilage - while avoiding cortisone preparations - should be discontinued if the success of treatment does not last significantly longer than the application. Satisfactory results can be obtained with the three basic operations such as proximolateral relief operation (longitudinal splitting of the retinacula), distal relief surgery (lifting of the tuberositas) and smoothening or more vertical excision of the focus of cartilaginification, in conjunction with further surgical interventions.

  1. Silk-hyaluronan-based composite hydrogels: a novel, securable vehicle for drug delivery.

    Science.gov (United States)

    Elia, Roberto; Newhide, Danny R; Pedevillano, Paul D; Reiss, G Russell; Firpo, Matthew A; Hsu, Edward W; Kaplan, David L; Prestwich, Glenn D; Peattie, Robert A

    2013-02-01

    A new, biocompatible hyaluronic acid (HA)-silk hydrogel composite was fabricated and tested for use as a securable drug delivery vehicle. The composite consisted of a hydrogel formed by cross-linking thiol-modified HA with poly(ethylene glycol)-diacrylate, within which was embedded a reinforcing mat composed of electrospun silk fibroin protein. Both HA and silk are biocompatible, selectively degradable biomaterials with independently controllable material properties. Mechanical characterization showed the composite tensile strength as fabricated to be 4.43 ± 2.87 kPa, two orders of magnitude above estimated tensions found around potential target organs. In the presence of hyaluronidase (HAse) in vitro, the rate of gel degradation increased with enzyme concentration although the reinforcing silk mesh was not digested. Composite gels demonstrated the ability to store and sustainably deliver therapeutic agents. Time constants for in vitro release of selected representative antibacterial and anti-inflammatory drugs varied from 46.7 min for cortisone to 418 min for hydrocortisone. This biocomposite showed promising mechanical characteristics for direct fastening to tissue and organs, as well as controllable degradation properties suitable for storage and release of therapeutically relevant drugs.

  2. Assessment and effective targeting of Interleukin-1 in multicentric reticulohistyocytosis.

    Science.gov (United States)

    Aouba, Achille; Leclerc-Mercier, Stéphanie; Fraitag, Sylvie; Martin-Silva, Nicolas; Bienvenu, Boris; Georgin-Lavialle, Sophie

    2015-07-01

    Multicentric reticulohistyocytosis (MRH) is a rare multisystemic non-Langerhans histiocytosis characterized by cutaneous nodules and severe destructive polyarthritis, sometimes associated with constitutional symptoms and various organ involvements. Its treatment remains empirical and challenging. We first report herein, the successful treatment of a multicentric reticulohistiocytosis patient with anakinra based on cutaneous biopsy immunostaining and serum cytokines features. A first-line treatment associating methotrexate, cortisone and hydoxychloroquine showed none improvement. Therefore, while further tests were performed to rule out an associated malignancy, auto-immune disease or mycobacterial infection, a treatment with anakinra was chosen instead of anti-TNF-alpha drugs. As soon as the 5th day, anakinra allowed control of fever, then rapid improvement of constitutional symptoms, arthritis, cutaneous lesions, and normalization of C-reactive protein, IL-6, and especially IL-1β levels. Then methotrexate was added, while anakinra was removed at the 12th month, with persistent and complete remission over the two-year follow up. Further assessment of IL-1 pathogenic role and blockade on larger cohorts of patient could open new therapeutic perspectives for refractory/relapsing MRH, considering the good tolerance profile of specific targeting drugs.

  3. Failure to infect laboratory rodent hosts with human isolates of Rodentolepis (= Hymenolepis) nana.

    Science.gov (United States)

    Macnish, M G; Morgan, U M; Behnke, J M; Thompson, R C A

    2002-03-01

    Confusion exists over the species status and host-specificity of the tapeworm Rodentolepis (= Hymenolepis) nana. It has been described as one species, R. nana, found in both humans and rodents. Others have identified a subspecies; R. nana var. fraterna, describing it as morphologically identical to the human form but only found in rodents. The species present in Australian communities has never been identified with certainty. Fifty one human isolates of Rodentolepis (= Hymenolepis) nana were orally inoculated into Swiss Q, BALB/c, A/J, CBA/ CAH and nude (hypothymic) BALB/c mice, Fischer 344 and Wistar rats and specific pathogen free (SPF) hamsters. Twenty four human isolates of R. nana were cross-tested in flour beetles, Tribolium confusum. No adult worms were obtained from mice, rats or hamsters, even when immunosuppressed with cortisone acetate. Only one of the 24 samples developed to the cysticercoid stage in T. confusum; however, when inoculated into laboratory mice the cysticercoids failed to develop into adult worms. The large sample size used in this study, and the range of techniques employed for extraction and preparation of eggs provide a comprehensive test of the hypothesis that the human strain of R. nana is essentially non-infective to rodents.

  4. A case of contact dermatitis to dimethylfumarate in shoes identified in Italy

    Directory of Open Access Journals (Sweden)

    Franca Davanzo

    2010-12-01

    Full Text Available The present paper describes a case of shoe contact dermatitis from DMF identified by the Poison Control Centre of Milan (PCCM, Italy, in 2009. A 35 year old woman was affected by irritant reactions while wearing shoes contaminated with DMF. Exposure to these shoes was limited to a 8 hour period and was not repeated. In the following days the patient suffered feet blistering and swelling limited to the area in contact with shoe vamp. Topical application of cortisone did not prevent development of bullous eczema. After 20 days from exposure, the lesions were healed but the skin remained red, dry and very sensitive. Chemical analyses of shoes quantified an average concentration of DMF of 383 mg/kg. The patient refused to be patch tested. The observation here reported confirm that DMF should be considered a possible causal agent in shoe contact dermatitis. Documentation of cases exposed to this chemical provide a relevant support to characterize clinical manifestations and to identifying contaminated articles.

  5. Environmental stress-induced testis differentiation: androgen as a by-product of cortisol inactivation.

    Science.gov (United States)

    Fernandino, Juan I; Hattori, Ricardo S; Moreno Acosta, Omar D; Strüssmann, Carlos A; Somoza, Gustavo M

    2013-10-01

    This review deals with the gonadal masculinization induced by thermal stress in fish with focus on the action of 11β-hydroxysteroid dehydrogenase (11β-HSD) as this mechanism key transducer. High temperatures have been reported to produce male-skewed sex ratios in several species with TSD (temperature-dependent sex determination), and in some of them, this process was reported to be associated with high levels of cortisol, the hormone-related stress in vertebrates, during early gonad development. In addition, in pejerrey larvae reared at high-masculinizing temperatures, 11-ketotestosterone (11-KT), the main and most potent androgen in fish, was also detected at high levels. In testicular explants, cortisol induced the synthesis of 11-KT, suggesting that its synthesis could be under the control of the stress axis at the time of gonadal fate determination. 11β-HSD is one of the enzymes shared by the glucocorticoid and androgen pathways; this enzyme converts cortisol to cortisone and also participates in the finals steps of the synthesis of the 11-oxigenated androgens. Based on these data and literature information, here we propose that the masculinization induced by thermal stress can be considered as a consequence of cortisol inactivation and the concomitant synthesis of 11-KT and discussing this as a possible mechanism of masculinization induced by different types of environmental stressors.

  6. The effect of polyphenol-rich dark chocolate on fasting capillary whole blood glucose, total cholesterol, blood pressure and glucocorticoids in healthy overweight and obese subjects.

    Science.gov (United States)

    Almoosawi, Suzana; Fyfe, Lorna; Ho, Clement; Al-Dujaili, Emad

    2010-03-01

    Numerous studies indicate that polyphenol-rich chocolate reduces fasting blood glucose, blood pressure (BP) and total cholesterol in healthy individuals and hypertensives with or without glucose intolerance. The aim of the present study was to investigate the effect of two doses of polyphenol-rich dark chocolate (DC) on fasting capillary whole blood glucose, total cholesterol and BP and to examine whether improvements in these parameters are associated with changes in adrenocorticoid excretion in overweight and obese individuals. The study used a randomised, single-blind, cross-over design where fourteen overweight and obese subjects were randomised to either take 20 g DC with 500 mg polyphenols then 20 g DC with 1000 mg polyphenols or vice-versa. Participants followed each diet for 2 weeks separated by a 1-week washout period. It was observed that the 500 mg polyphenol dose was equally effective in reducing fasting blood glucose levels, systolic BP (SBP) and diastolic BP (DBP) as the 1000 mg polyphenol dose suggesting that a saturation effect might occur with increasing dose of polyphenols. There was also a trend towards a reduction in urinary free cortisone levels with both groups although it did not reach statistical significance. No changes in anthropometrical measurements were seen. We suggest that more research is required to investigate the mechanism(s) by which polyphenol-rich foods influence health.

  7. Absence of Fungal Spore Internalization by Bronchial Epithelium in Mouse Models Evidenced by a New Bioimaging Approach and Transmission Electronic Microscopy.

    Science.gov (United States)

    Rammaert, Blandine; Jouvion, Grégory; de Chaumont, Fabrice; Garcia-Hermoso, Dea; Szczepaniak, Claire; Renaudat, Charlotte; Olivo-Marin, Jean-Christophe; Chrétien, Fabrice; Dromer, Françoise; Bretagne, Stéphane

    2015-09-01

    Clinical data and experimental studies suggest that bronchial epithelium could serve as a portal of entry for invasive fungal infections. We therefore analyzed the interactions between molds and the bronchial/bronchiolar epithelium at the early steps after inhalation. We developed invasive aspergillosis (Aspergillus fumigatus) and mucormycosis (Lichtheimia corymbifera) murine models that mimic the main clinical risk factors for these infections. Histopathology studies were completed with a specific computer-assisted morphometric method to quantify bronchial and alveolar spores and with transmission electron microscopy. Morphometric analysis revealed a higher number of bronchial/bronchiolar spores for A. fumigatus than L. corymbifera. The bronchial/bronchiolar spores decreased between 1 and 18 hours after inoculation for both fungi, except in corticosteroid-treated mice infected with A. fumigatus, suggesting an effect of cortisone on bronchial spore clearance. No increase in the number of spores of any species was observed over time at the basal pole of the epithelium, suggesting the lack of transepithelial crossing. Transmission electron microscopy did not show spore internalization by bronchial epithelial cells. Instead, spores were phagocytized by mononuclear cells on the apical pole of epithelial cells. Early epithelial internalization of fungal spores in vivo cannot explain the bronchial/bronchiolar epithelium invasion observed in some invasive mold infections. The bioimaging approach provides a useful means to accurately enumerate and localize the fungal spores in the pulmonary tissues.

  8. Are there characteristic alterations in lung tissue associated with Crohn's disease?

    Science.gov (United States)

    Kayser, K; Probst, F; Gabius, H J; Müller, K M

    1990-08-01

    Two male patients aged 12 and 31 years suffered from Crohn's disease for more than six years and were treated with Cortison for more than four years. Surgical excision of parts of the terminal ileum was performed in both patients. They suffered from pulmonary symptoms as dyspnoea, shortness of breath and ventilation disturbances two years after operation. Wedge biopsies of the lungs revealed the following histomorphological findings: 1. Granulomatous interstitial lymphocyte infiltrates 2. Acute alveolitis with severe dysplasia of pneumocytes 3. Moderate interstitial fibrosis. Immunohistology performed in one case showed predominantly lambda chains expressed by lymphocytes associated with IgA and IgM. IgG was missing, furthermore kappa chains could not be detected. Macrophages contained endogenous lectins (sugar receptors) for fucose, maltose, and N-acetyl-D-glucosamine (glcNAc). No receptors specific for mannose, lactose, and heparin could be found. Pneumocytes did not bind the neoglycoproteins but were found to express HLA-DR receptors detectable by the monoclonal antibody LN 3 in dysplastic pneumocytes only. The histomorphological and immunohistochemical findings suggest that the analyzed alterations of lung tissue are related to the underlying disease of enteritis regionalis.

  9. Microbial degradation of fluorinated drugs: biochemical pathways, impacts on the environment and potential applications.

    Science.gov (United States)

    Murphy, Cormac D

    2016-03-01

    Since the discovery over 60 years ago of fluorocortisone's biological properties (9-α-Fluoro derivatives of cortisone and hydrocortisone; Fried J and Sabo EF, J Am Chem Soc 76: 1455-1456, 1954), the number of fluorinated drugs has steadily increased. With the improvement in synthetic methodologies, this trend is likely to continue and will lead to the introduction of new fluorinated substituents into pharmaceutical compounds. Although the biotransformation of organofluorine compounds by microorganisms has been well studied, specific investigations on fluorinated drugs are relatively few, despite the increase in the number and variety of fluorinated drugs that are available. The strength of the carbon-fluorine bond conveys stability to fluorinated drugs; thus, they are likely to be recalcitrant in the environment or may be partially metabolized to a more toxic metabolite. This review examines the research done on microbial biotransformation and biodegradation of fluorinated drugs and highlights the importance of understanding how microorganisms interact with this class of compound from environmental, clinical and biotechnological perspectives.

  10. 大鼠中性粒细胞与滑膜细胞粘附模型的建立%ESTABLISHMENT OF A MODEL FOR ADHESION OF POLYMORPHONUCLEAR LEUKOCYTE TO SYNOVIAL CELL

    Institute of Scientific and Technical Information of China (English)

    李良成; 侯琦; 程桂芳; 张成义

    2000-01-01

    目的:建立大鼠中性粒细胞(PMN)与滑膜细胞(RSC)的粘附模型.方法:MTT比色法.结果:500U·mL-1rhTNF-α与IL-1刺激RSC12h对PMN有明显的粘附作用,MTT-PMN细胞数与540nm吸光度值有良好的线形相关性;氢化考的松(hydrocortisone,Hy)和美洛昔康(meloxicam,Melo)均可抑制PMN与500U·mL-1rhTNF-α/或IL-1诱导的RSC粘附,提示Hy和Melo治疗类风湿性关节炎(RA)可能与其抑制PMN与RSC粘附作用有关.结论:以MTT比色法为基础建立的检测大鼠PMN与RSC的粘附模型,可用于PMN与RSC粘附抑制剂的筛选.

  11. The role of 11?-hydroxysteroid dehydrogenase type 1 and type2 isoenzymes on the pathogenesis of Cushing’s syndrome - doi:10.5020/18061230.2007.p104

    Directory of Open Access Journals (Sweden)

    Maria Betânia Pereira Toralles

    2012-01-01

    Full Text Available The action of glucocorticoids is modulated by isoenzymes 11?-hidroxiesteróide desidrogenases (11?-HSD type 1 and 2. The knowledge concerning these isoenzymes contribute to the understanding of the regulatory mechanisms involved in several disease processes of the Cushing’s syndrome, such as obesity, osteoporosis and hypertension. With the aim at describing the action of isoenzymes 11?-HSD type 1 and 2 in the Cushing’s syndrome, a literature review was done from 1990 - 2006 using the Medline data base, searching for the following key-words: Cushing’s syndrome, glucocorticoids, 11?-hydroxysteroid dehydrogenase, hypertension, osteoporosis and obesity. Review studies, meta-analysis and original articles were selected and chosen on the basis of methodological aspects and relevance. The exact mechanism by which cortisol increases blood pressure is not completely understood, but it involves, among others factors, changes in the sodium homeostasis. The conversion of cortisone to cortisol through expression of 11?-HSD1 induces the differentiation of preadipoctyes to mature adipoctyes and such patients develop an increase in visceral fat. The prevalence of osteoporosis in adult patients with Cushing’s syndrome is approximately 50% and glucocorticoids play a strong effect on the bone and calcium metabolism. The isoenzymes 11?-HSD1 and 11?-HSD2 have an important function in these several pathophysiology processes; however the isoenzymes action in the pathophysiology of the Cushing’s syndrome need to be more investigated.

  12. Premature adrenarche: novel lessons from early onset androgen excess.

    Science.gov (United States)

    Idkowiak, Jan; Lavery, Gareth G; Dhir, Vivek; Barrett, Timothy G; Stewart, Paul M; Krone, Nils; Arlt, Wiebke

    2011-08-01

    Adrenarche reflects the maturation of the adrenal zona reticularis resulting in increased secretion of the adrenal androgen precursor DHEA and its sulphate ester DHEAS. Premature adrenarche (PA) is defined by increased levels of DHEA and DHEAS before the age of 8 years in girls and 9 years in boys and the concurrent presence of signs of androgen action including adult-type body odour, oily skin and hair and pubic hair growth. PA is distinct from precocious puberty, which manifests with the development of secondary sexual characteristics including testicular growth and breast development. Idiopathic PA (IPA) has long been considered an extreme of normal variation, but emerging evidence links IPA to an increased risk of developing the metabolic syndrome (MS) and thus ultimately cardiovascular morbidity. Areas of controversy include the question whether IPA in girls is associated with a higher rate of progression to the polycystic ovary syndrome (PCOS) and whether low birth weight increases the risk of developing IPA. The recent discoveries of two novel monogenic causes of early onset androgen excess, apparent cortisone reductase deficiency and apparent DHEA sulphotransferase deficiency, support the notion that PA may represent a forerunner condition for PCOS. Future research including carefully designed longitudinal studies is required to address the apparent link between early onset androgen excess and the development of insulin resistance and the MS.

  13. Defensive coping and renovascular disease risk - Adrenal fatigue in a cohort of Africans and Caucasians: The SABPA study.

    Science.gov (United States)

    de Kock, Andrea; Malan, Leoné; Hamer, Mark; Cockeran, Marike; Malan, Nico T

    2015-08-01

    Defensive coping is an established cardiovascular risk factor in Africans. Additionally, chronic, excessive or inadequate hypothalamic-pituitary-adrenal axis (HPAA) stress responses could either increase or decrease cortisol responses, which may relate to renal impairment. We scrutinised the relationship between urinary cortisol levels and renovascular disease risk in Africans and Caucasians utilising defensive coping. Africans (n=168) and Caucasians (n=207) from the SABPA (Sympathetic activity and Ambulatory Blood Pressure in Africans) study were included in our analyses, excluding HIV positive, diabetic, renal impairment, and cortisone users. The Coping Strategy Indicator questionnaire assessed preferred coping responses. Ambulatory blood pressure was recorded together with 8h fasting blood and urine sampling. Renovascular disease risk markers included the albumin-to-creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR). The main findings revealed that Caucasians with high cortisol showed augmented renovascular disease risk. Conversely, Africans revealed low cortisol levels whilst 21.84% reported experience of severe stress, possibly depicting HPAA hypoactivity. Additionally, these Africans with low cortisol revealed increased ACR and decreased eGFR, which was further enhanced by defensive coping. Defensive coping enhanced renovascular risk in Africans, especially in those with lower cortisol, which may be due to HPAA dysfunction and/or adrenal fatigue. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Gender differences in inflammatory proteins and pathways in seasonal allergic rhinitis.

    Science.gov (United States)

    Barrenäs, Fredrik; Andersson, Bengt; Cardell, Lars Olaf; Langston, Michael; Mobini, Reza; Perkins, Andy; Soini, Juhani; Ståhl, Arne; Benson, Mikael

    2008-06-01

    In model organisms, thousands of genes differ in expression between females and males. It is not known if differences on a similar scale are found in humans nor how this relates to disease. However, in allergic disease gender differences in the levels of both inflammatory cells and proteins have been shown. In this study, we found lower nasal fluid allergen-specific IgE in women than men with seasonal allergic rhinitis (SAR). This led to genome-wide analyses of gene expression in allergen-challenged CD4(+) cells from patients with SAR before and after treatment with cortisone. Before treatment, 975 genes differed in expression between women and men: 337 were higher in women. After treatment only 428 genes and one pathway differed in expression. The genes that differed in expression between women and men were over-represented in 10 pathways. Five of the pathways regulated chemotaxis. All five were less active in women. One of the pathways was induced by the eosinophilic chemokine CCL4. Analysis of nasal fluid CCL4 protein confirmed lower levels in women with seasonal allergic rhinitis, before and during the pollen season. By contrast, nasal fluid CCL3 levels did not differ between the genders. In summary, this study shows gender differences in specific inflammatory pathways and proteins in patients with seasonal allergic rhinitis. Further studies are warranted to examine if such differences have diagnostic and therapeutic implications in allergic diseases.

  15. Using Snacks High in Fat and Protein to Improve Glucoregulatory Function in Adolescent Male Marmosets (Callithrix jacchus)

    Science.gov (United States)

    Ziegler, Toni E; Sosa, Megan E; Peterson, Laura J; Colman, Ricki J

    2013-01-01

    The common marmoset (Callithrix jacchus), a laboratory nonhuman primate, is a well-known model of several human diseases and conditions, but the nutritional needs of these animals are not fully understood. Here we describe a 4-mo controlled study in which we increased the dietary fat and protein of subadult male common marmosets by using healthy snacks. Six male marmosets received their normal diet (control), and an additional 6 were given their normal diet supplemented daily with a 14-kcal snack. Cashews and waxworms were used as the snack, given their high-fat content. Although body weight did not differ between the 2 groups, only control male marmosets showed increased chest circumferences over the course of the study. Glucoregulatory function remained consistent in the snack-fed marmosets, whereas control animals had progressed toward higher insulin. Other indices of glucoregulation indicated significant differences in adiponectin and the cortisol:cortisone ratio between the 2 groups, but no differences in lipid concentration were detected. Therefore, the most notable difference attributable to the snack feeding was improved glucoregulation. Because the snacks we used had a high proportion of unsaturated compared with saturated fat, we suggest that these healthy high-fat–high-protein snacks provide an important contribution to the nutrition of this laboratory species. This study also demonstrates the utility of marmosets as a model for understanding the implications of dietary fats in humans. PMID:24351764

  16. [Regenerative medicine: orthopaedical applications and medico legal questions].

    Science.gov (United States)

    Ricci, S; Ricci, O; Tucci, C E; Massoni, F; Sarra, M V; Ricci, S

    2012-01-01

    Over the last decades, the increase in the global population's mean age has implied a corresponding increase in degenerative disease affecting various anatomical areas and tissues, including bones and cartilages, thus provoking a rising number of disabilities and a wider usage of drugs, mostly anti-inflammatory and cortisone. New developments in technologic and biomedical fields gave birth to new subjects, such as tissue engineering, cell therapy, gene therapy that, by and large, create a knowledge network falling under the concept of Regenerative Medicine. This science is essentially based on the usage of stem cells that can replicate and renovate themselves originating, if adequately stimulated, a number of cell types. Inter alia, in orthopaedic field a particular type of adult stem cells is used, the mesenchymal stem cells (MSCs). If combined with synthetic material produced in laboratories, the usage of these cells has provided inspiration for new study interests; today, it can be applied in various degenerative and post-traumatic pathologies, with great therapeutic benefits for the patient. Actually, many studies write about an improvement in patients' life quality. In this sense appear significant reflections on legal medicine, both in accidents and insurance, of this innovative therapeutic alternative and is hopefully an equally valid process of improvement of regulatory and case law.

  17. An UPLC-MS-based metabolomics investigation on the anti-fatigue effect of salidroside in mice.

    Science.gov (United States)

    Ma, Chaoyang; Hu, Liming; Tao, Guanjun; Lv, Wenping; Wang, Hongxin

    2015-02-01

    An ultra-performance liquid chromatography-quadrupole time-of-flight-based metabolomic approach was developed to study influence of salidroside, an anti-fatigue ingredient from Rhoiola rosea, on urinary metabolic profiling of rats to a single dose of 180 mg/kg per day. Unsupervised principal component analysis (PCA) and supervised orthogonal pre-projection to latent structures discriminate analysis (OPLS-DA) on metabolite profiling revealed obvious differentiation between the salidroside treated groups and controls in both positive and negative ion modes. Eleven urinary metabolites contributing to the differentiation were identified as anti-fatigue biomarkers: N-acetylserotonin, 2-Methoxyestrone 3-glucuronide, Taurine, Melatonin, Sorbitol, Geranyl diphosphate, Z-nucleotide, Cortisone, Dihydrocortisol, Sebacic acid, Pregnenolone sulfate. The physiological significance of these biomarkers is discussed. The work showed that metabolomics is a powerful tool in studying the anti-fatigue effects of natural compound salidroside on multiple targets in vivo. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Growth hormone (GH) substitution in GH-deficient patients inhibits 11beta-hydroxysteroid dehydrogenase type 1 messenger ribonucleic acid expression in adipose tissue.

    Science.gov (United States)

    Paulsen, Søren Kildeberg; Pedersen, Steen Bønløkke; Jørgensen, Jens Otto Lunde; Fisker, Sanne; Christiansen, Jens Sandahl; Flyvbjerg, Allan; Richelsen, Bjørn

    2006-03-01

    Local tissue activity of glucocorticoids is in part determined by the isoenzymes 11beta-hydroxysteroid dehydrogenase 1 (11beta-HSD1) and 11beta-HSD2, interconverting inert cortisone and active cortisol. Increased tissue activity of cortisol may play a central role in the features of GH deficiency and the metabolic syndrome. We investigated the effects of GH treatment on adipose tissue 11beta-HSD mRNA. A randomized placebo-controlled double-blind study design was used. Twenty-three GH-deficient patients (16 males and seven females) were randomized to 4 months of GH treatment (2 IU/m2) (n = 11) or placebo treatment (n = 12). Adipose tissue biopsies and blood samples were obtained before and after treatment. Biopsies were obtained from the abdominal sc depot at the level of the umbilicus and do not necessarily reflect the metabolically more important visceral adipose tissue. Gene expressions were determined by real-time RT-PCR. GH treatment decreased 11beta-HSD1 mRNA 66% [95% confidence interval (CI), 23-107%; P adipose tissue. Serum IGF-I and IGF-I mRNA increased in the GH-treated group by 187% (95% CI, 122-250%; P cortisol in adipose tissue.

  19. T cell-mediated inflammation in adipose tissue does not cause insulin resistance in hyperlipidemic mice.

    Science.gov (United States)

    Sultan, Ariane; Strodthoff, Daniela; Robertson, Anna-Karin; Paulsson-Berne, Gabrielle; Fauconnier, Jeremy; Parini, Paolo; Rydén, Mikael; Thierry-Mieg, Nicolas; Johansson, Maria E; Chibalin, Alexander V; Zierath, Juleen R; Arner, Peter; Hansson, Göran K

    2009-04-24

    Obesity is associated with chronic inflammation in adipose tissue. Proinflammatory cytokines including tumor necrosis factor-alpha and interleukin-6 secreted by adipose tissue during the metabolic syndrome are proposed to cause local and general insulin resistance and promote development of type 2 diabetes. We have used a compound mutant mouse, Apoe(-/-)xCD4dnTGFbR, with dysregulation of T-cell activation, excessive production of proinflammatory cytokines, hyperlipidemia, and atherosclerosis, to dissect the role of inflammation in adipose tissue metabolism. These mice are lean, which avoids confounding effects of concomitant obesity. Expression and secretion of a set of proinflammatory factors including tumor necrosis factor-alpha, interferon-gamma, and monocyte chemoattractant protein-1 was increased in adipose tissue of Apoe(-/-)xCD4dnTGFbR mice, as was the enzyme 11beta-hydroxysteroid dehydrogenase type 1, which converts cortisone to bioactive cortisol. Interleukin-6, which has an inhibitory glucocorticoid response element in its promoter, was not upregulated. In spite of intense local inflammation, insulin sensitivity was not impaired in adipose tissue of Apoe(-/-)xCD4dnTGFbR mice unless exogenous interleukin-6 was administered. In conclusion, T-cell activation causes inflammation in adipose tissue but does not lead to insulin resistance in this tissue in the absence of interleukin-6.

  20. Estrogen reduces 11beta-hydroxysteroid dehydrogenase type 1 in liver and visceral, but not subcutaneous, adipose tissue in rats.

    Science.gov (United States)

    Andersson, Therése; Söderström, Ingegerd; Simonyté, Kotryna; Olsson, Tommy

    2010-03-01

    Following menopause, body fat is redistributed from peripheral to central depots. This may be linked to the age related decrease in estrogen levels. We hypothesized that estrogen supplementation could counteract this fat redistribution through tissue-specific modulation of glucocorticoid exposure. We measured fat depot masses and the expression and activity of the glucocorticoid-activating enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1) in fat and liver of ovariectomized female rats treated with or without 17beta-estradiol. 11betaHSD1 converts inert cortisone, or 11-dehydrocorticosterone in rats into active cortisol and corticosterone. Estradiol-treated rats gained less weight and had significantly lower visceral adipose tissue weight than nontreated rats (P adipose weight was unaltered. In addition, 11betaHSD1 activity/expression was downregulated in liver and visceral, but not subcutaneous, fat of estradiol-treated rats (P adipose tissue depots, with higher levels in subcutaneous than visceral adipose tissue of estradiol-treated animals (P effects on tissue-specific glucocorticoid metabolism, suggesting that estrogen replacement therapy could influence obesity related morbidity in postmenopausal women.

  1. Upregulation of adipose 11-beta-hydroxysteroid dehydrogenase type 1 expression in ovariectomized rats is due to obesity rather than lack of estrogen.

    Science.gov (United States)

    Paulsen, Søren K; Nielsen, Maria P; Richelsen, Bjørn; Bruun, Jens M; Flyvbjerg, Allan; Pedersen, Steen B

    2008-04-01

    Increased tissue activity of cortisol induced by the activation of inert cortisone to active cortisol through 11-beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) may play a role in the metabolic syndrome. We recently found that 11beta-HSD1 in subcutaneous adipose tissue (AT) was lower in lean women compared with lean men. Estrogen suppresses hepatic and renal 11beta-HSD1 in rats; hence we investigated the in vitro effect of estrogen on human and rat AT, and the in vivo effects on rat AT 11beta-HSD1 expression. Wistar rats were divided into four groups of eight animals. One group was sham-operated (controls) and others were ovariectomized (OVX). One OVX group was left untreated (OVX-E), another (OVX+E) received estrogen treatment, and one received a hypo-caloric diet (OVX-E+D), matching the weight gain of the control group. AT from women undergoing liposuction or surgery and from killed male and female rats were incubated with estrogen alone or in the presence of IL-1beta. Gene expressions were determined by real-time reverse transcriptase PCR. Ovariectomy resulted in a 280% increase in adipose 11beta-HSD1 expression P effect of estrogen on adipose 11beta-HSD1 was found. The upregulation of 11beta-HSD1 in ovariectomized rats was most likely due to changes in body composition rather than lack of estrogen.

  2. Cortisol intermediates and hydrocortisone responsiveness in critical neonatal disease.

    Science.gov (United States)

    Khashana, Abdelmoneim; Saarela, Timo; Ramet, Mika; Hallman, Mikko

    2017-07-01

    Therapy-resistant hypotension complicates diseases in neonates. Our objective was to investigate whether lack of therapeutic response to plasma expanders and inotropes associates with serum levels of cortisol and its precursors. We investigated 96 infants with hypotension and critical neonatal disease for cortisol metabolism and are divided into responders and non-responders to plasma expanders and inotropes. Serum concentrations of steroids were analysed soon after the onset of volume expansion and inotrope treatment for shock. The 48 non-responders were treated with intravenous hydrocortisone (HC) and serum cortisol concentrations were monitored a week later. The mean cortisol concentrations did not differ between the responders and non-responders: 13.6 ± 2.5 and 12.5 ± 4.5 μg/dL, respectively. Dehydroepiandrosterone (37.3 ± 19.5 versus 324.0 ± 106.3; p cortisol and cortisone between the responders and non-responders. Hydrocortisone administration acutely increased blood pressure. Six non-responders who died despite HC administration had low levels of cortisol. The responders had normal serum cortisol after HC treatment. Precursors of cortisol, proximal to the 3β-hydroxysteroid dehydrogenase activity, accumulated in neonates with hypotension, responding to HC treatment.

  3. Animal models of candidiasis.

    Science.gov (United States)

    Clancy, Cornelius J; Cheng, Shaoji; Nguyen, Minh Hong

    2009-01-01

    Animal models are powerful tools to study the pathogenesis of diverse types of candidiasis. Murine models are particularly attractive because of cost, ease of handling, technical feasibility, and experience with their use. In this chapter, we describe methods for two of the most popular murine models of disease caused by Candida albicans. In an intravenously disseminated candidiasis (DC) model, immunocompetent mice are infected by lateral tail vein injections of a C. albicans suspension. Endpoints include mortality, tissue burdens of infection (most importantly in the kidneys, although spleens and livers are sometimes also assessed), and histopathology of infected organs. In a model of oral/esophageal candidiasis, mice are immunosuppressed with cortisone acetate and inoculated in the oral cavities using swabs saturated with a C. albicans suspension. Since mice do not die from oral candidiasis in this model, endpoints are tissue burden of infection and histopathology. The DC and oral/esophageal models are most commonly used for studies of C. albicans virulence, in which the disease-causing ability of a mutant strain is compared with an isogenic parent strain. Nevertheless, the basic techniques we describe are also applicable to models adapted to investigate other aspects of pathogenesis, such as spatiotemporal patterns of gene expression, specific aspects of host immune response and assessment of antifungal agents, immunomodulatory strategies, and vaccines.

  4. Virtual reality jogging as a novel exposure paradigm for the acute urge to be physically active in patients with eating disorders: Implications for treatment.

    Science.gov (United States)

    Paslakis, Georgios; Fauck, Vanessa; Röder, Kathrin; Rauh, Elisabeth; Rauh, Manfred; Erim, Yesim

    2017-08-11

    The acute urge to be physically active is a relevant clinical phenomenon in patients suffering from eating disorders. In this study with n = 20 female patients with anorexia nervosa and n = 10 female patients with bulimia nervosa, a virtual reality (VR) jogging paradigm was applied as a novel highly immersive 3-D exposure paradigm. Patients were asked to rate their acute urge to be physically active during the exposure procedure. A 10-item self-report questionnaire (smQ) was developed to capture the cognitive, emotional, and behavioral aspects of the acute urge to move. We hypothesized that exposure would lead to habituation of the urge to be physically active. We also hypothesized that leptin levels would be associated with the degree of the subjective urge to be physically active, while habituation would be associated with a decrease in stress hormones (α-amylase, cortisol, and cortisone in saliva). A statistically significant change in subjective scores in the smQ from baseline to postexposure was seen. Our novel VR paradigm may serve as a therapeutic tool for exposure and habituation of the urge of acutely engaging in physical activity in patients with eating disorders. © 2017 Wiley Periodicals, Inc.

  5. Novel non-steroidal inhibitors of human 11beta-hydroxysteroid dehydrogenase type 1.

    Science.gov (United States)

    Vicker, Nigel; Su, Xiangdong; Ganeshapillai, Dharshini; Smith, Andrew; Purohit, Atul; Reed, Michael J; Potter, Barry V L

    2007-05-01

    11beta-Hydroxysteroid dehydrogenase type 1 (11beta-HSD1) regulates glucocorticoid action at the pre-receptor stage by converting cortisone to cortisol. 11beta-HSD1 is selectively expressed in many tissues including the liver and adipose tissue where metabolic events are important. Metabolic syndrome relates to a number of metabolic abnormalities and currently has a prevalence of >20% in adult Americans. 11beta-HSD1 inhibitors are being investigated by many major pharmaceutical companies for type 2 diabetes and other abnormalities associated with metabolic syndrome. In this area of intense interest a number of structural types of 11beta-HSD1 inhibitor have been identified. It is important to have an array of structural types as the physicochemical properties of the compounds will determine tissue distribution, HPA effects, and ultimately clinical utility. Here we report the discovery and synthesis of three structurally different series of novel 11beta-HSD1 inhibitors that inhibit human 11beta-HSD1 in the low micromolar range. Docking studies with 1-3 into the crystal structure of human 11beta-HSD1 reveal how the molecules may interact with the enzyme and cofactor and give further scope for structure based drug design in the optimisation of these series.

  6. Adamantyl ethanone pyridyl derivatives: potent and selective inhibitors of human 11β-hydroxysteroid dehydrogenase type 1.

    Science.gov (United States)

    Su, Xiangdong; Pradaux-Caggiano, Fabienne; Vicker, Nigel; Thomas, Mark P; Halem, Heather; Culler, Michael D; Potter, Barry V L

    2011-09-05

    Elevated levels of active glucocorticoids have been implicated in the development of several phenotypes of metabolic syndrome, such as type 2 diabetes and obesity. 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) catalyses the intracellular conversion of inactive cortisone to cortisol. Selective 11β-HSD1 inhibitors have shown beneficial effects in various conditions, including diabetes, dyslipidemia and obesity. A series of adamantyl ethanone pyridyl derivatives has been identified, providing potent and selective inhibitors of human 11β-HSD1. Lead compounds display low nanomolar inhibition against human and mouse 11β-HSD1 and are selective for this isoform, with no activity against 11β-HSD2 and 17β-HSD1. Structure-activity relationship studies reveal that an unsubstituted pyridine tethered to an adamantyl ethanone motif through an ether or sulfoxide linker provides a suitable pharmacophore for activity. The most potent inhibitors have IC₅₀ values around 34-48 nM against human 11β-HSD1, display reasonable metabolic stability in human liver microsomes, and weak inhibition of key human CYP450 enzymes.

  7. Adamantyl Ethanone Pyridyl Derivatives: Potent and Selective Inhibitors of Human 11β-Hydroxysteroid Dehydrogenase Type 1

    Science.gov (United States)

    Su, Xiangdong; Pradaux-Caggiano, Fabienne; Vicker, Nigel; Thomas, Mark P; Halem, Heather; Culler, Michael D; Potter, Barry V L

    2011-01-01

    Elevated levels of active glucocorticoids have been implicated in the development of several phenotypes of metabolic syndrome, such as type 2 diabetes and obesity. 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) catalyses the intracellular conversion of inactive cortisone to cortisol. Selective 11β-HSD1 inhibitors have shown beneficial effects in various conditions, including diabetes, dyslipidemia and obesity. A series of adamantyl ethanone pyridyl derivatives has been identified, providing potent and selective inhibitors of human 11β-HSD1. Lead compounds display low nanomolar inhibition against human and mouse 11β-HSD1 and are selective for this isoform, with no activity against 11β-HSD2 and 17β-HSD1. Structure–activity relationship studies reveal that an unsubstituted pyridine tethered to an adamantyl ethanone motif through an ether or sulfoxide linker provides a suitable pharmacophore for activity. The most potent inhibitors have IC50 values around 34–48 nm against human 11β-HSD1, display reasonable metabolic stability in human liver microsomes, and weak inhibition of key human CYP450 enzymes. PMID:21714097

  8. No effect of free fatty acids on adrenocorticotropin and cortisol secretion in healthy young men.

    Science.gov (United States)

    Mai, Knut; Bobbert, Thomas; Kullmann, Volker; Andres, Janin; Bähr, Volker; Maser-Gluth, Christiane; Rochlitz, Helmut; Spranger, Jochen; Diederich, Ssven; Pfeiffer, Andreas F H

    2006-08-01

    Free fatty acids (FFAs) affect anterior pituitary function. However, the effect of FFAs on corticotropin (ACTH) and cortisol in humans is controversial. Thus, we assessed the effect of a pronounced increase in circulating FFA levels induced by infusion of lipid/heparin on ACTH and cortisol secretion in young men. Eight healthy male volunteers who underwent a 10-hour overnight fast were investigated. A 20% lipid/heparin or saline/heparin infusion was given at a rate of 1.5 mL/min for 6 hours. A euglycemic hyperinsulinemic clamp was performed in 6 subjects 4 hours after the start of infusion. To assess steroid metabolism, we measured ACTH, cortisol, FFAs, and urinary steroids. Lipid infusion increased FFAs (6.06 +/- 0.52 vs 0.70 +/- 0.23 mmol/L; P < .005) and induced insulin resistance (glucose infusion rate, 4.08 +/- 2.15 vs 6.02 +/- 2.60 mg/kg per minute; P < .005). Serum cortisol and plasma ACTH decreased independent of lipid/heparin or saline/heparin infusion. In addition, we found no effect of hyperinsulinemia on ACTH and cortisol levels. There were no differences in urinary free cortisol, urinary free cortisone, 5beta-tetrahydrocortisol, 5alpha-tetrahydrocortisol, and tetrahydrocortisone. In conclusion, FFAs had no effect on basal ACTH and cortisol secretion in normal-weight young men. In addition, no alterations in urinary glucocorticoid metabolites were detected, suggesting unchanged cortisol metabolism during lipid infusion.

  9. Combination of Estrogen and Immunosuppressive Agents to Establish a Mouse Model of Candidiasis with Concurrent Oral and Vaginal Mucosal Infection.

    Science.gov (United States)

    Wang, Le; Wang, Chong; Mei, Huan; Shen, Yongnian; Lv, Guixia; Zeng, Rong; Zhan, Ping; Li, Dongmei; Liu, Weida

    2016-02-01

    Mouse model is an appropriate tool for pathogenic determination and study of host defenses during the fungal infection. Here, we established a mouse model of candidiasis with concurrent oral and vaginal mucosal infection. Two C. albicans strains sourced from clinical candidemia (SC5314) and mucosal infection (ATCC62342) were tested in ICR mice. The different combinational panels covering estrogen and immunosuppressive agents, cortisone, prednisolone and cyclophosphamide were used for concurrent oral and vaginal candidiasis establishment. Prednisolone in combination with estrogen proved an optimal mode for concurrent mucosal infection establishment. The model maintained for 1 week with fungal burden reached at least 10(5) cfu/g of tissue. This mouse model was evaluated by in vivo pharmacodynamics of fluconazole and host mucosal immunity of IL-17 and IL-23. Mice infected by SC5314 were cured by fluconazole. An increase in IL-23 in both oral and vaginal homogenates was observed after infection, while IL-17 only had a prominent elevation in oral tissue. This model could properly mimic complicated clinical conditions and provides a valuable means for antifungal assay in vivo and may also provide a useful method for the evaluation of host-fungal interactions.

  10. 代谢综合征与抑郁症的相关性%Relationship between metabolic syndrome and depression

    Institute of Scientific and Technical Information of China (English)

    周建新; 陈莉明

    2011-01-01

    近年来随着代谢综合征发病率的升高,其并发抑郁症的人数也相应增加.代谢综合征中的胰岛素抵抗、皮质醇增多、肥胖和非酒精性脂肪肝与抑郁症的发生有关,而抑郁症患者的不健康生活习惯又是发生代谢综合征的原因.而且两种疾病的治疗也存在交叉.探索二者之间的关系,有助于进一步研究其发病机制,预防和治疗代谢综合征相关性抑郁症.%With the increase of prevalance of metabolic syndrome, the number of the patients suffering from depression is increasing. Depression in the patients with metabolic syndrome is associated with insulin resistance,higher level of cortisone,obesity and nonalcoholic fatty liver. And the unhealthy life style of depressive patients will then aggravate metabolic syndrome. Furthermore the treatment of these two diseases has the same aspects. The exploration of the association between depression and metabolic syndrome is helpful in understanding of the pathogenesis,prevention and treatment of depression related to metabolic syndrome.

  11. Two Qatari siblings with cystic fibrosis and apparent mineralocorticoid excess

    Directory of Open Access Journals (Sweden)

    Khalid Zahraldin

    2015-01-01

    Full Text Available Cystic fibrosis (CF and apparent mineralocorticoid excess (AME syndrome are both autosomal recessive disorders that result from mutations of specific identified genes for each condition. CF is caused by defects in the Cystic fibrosis trans membrane conductance regulator (CFTR gene which encodes for a protein that functions as a chloride channel and regulates the flow of other ions across the apical surface of epithelial cells. AME is due to the deficiency of 11β-hydroxysteroid dehydrogenase type 2 enzyme (11βHSD2, which is responsible for the peripheral inactivation of cortisol to cortisone. Cortisol excess stimulates the mineralocoritoid receptors (MR resulting in intense sodium retention, hypokalemia and hypertension. We report on a consanguineous Arab family, in which two sibs inherited both CF and AME. Gene testing for AME revealed previously unreported mutation in the 11βHSD2 gene. This report draws attention to the importance of recognizing the possibility of two recessive disorders in the same child in complex consanguineous families. Moreover, it provides a unique opportunity to highlight the implications of the coexistence of two genetic disorders on patient care and genetic counseling of the family.

  12. Hair cortisol as a biological marker for burnout symptomatology.

    Science.gov (United States)

    Penz, Marlene; Stalder, Tobias; Miller, Robert; Ludwig, Vera M; Kanthak, Magdalena K; Kirschbaum, Clemens

    2017-07-23

    Burnout is a syndrome with negative impact on cognitive performance and mood as a consequence of long-term stress at work. It is further associated with increased risk for mental and physical diseases. One potential pathway to mediate chronic work-stress and adverse health conditions in burnout is through alterations in long-term glucocorticoid secretion. Here, we present cross-sectional data on hair cortisol/cortisone (hairF/hairE) concentrations and burnout from a population-based sample of the Dresden Burnout Study (DBS; N=314 hair samples). Burnout symptoms (emotional exhaustion, cynical attitudes toward work, and reduced efficacy) were assessed with the Maslach Burnout Inventory-General Survey (MBI-GS). To control for potential confounds, depressivity was as well assessed using the Patient Health Questionnaire (PHQ-9) screening instrument for major depression. The present findings indicate specific hypercortisolism in participants who suffer from burnout. No significant associations were found between depressivity and hairF/hairE. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. The Aspergillus fumigatus Transcription Factor Ace2 Governs Pigment Production, Conidiation and Virulence

    Science.gov (United States)

    Ejzykowicz, Daniele E.; Cunha, Marcel M.; Rozental, Sonia; Solis, Norma V.; Gravelat, Fabrice N.; Sheppard, Donald C.; Filler, Scott G.

    2009-01-01

    Summary Aspergillus fumigatus causes serious and frequently fatal infections in immunocompromised patients. To investigate the regulation of virulence of this fungus, we constructed and analyzed an A. fumigatus mutant that lacked the transcription factor Ace2, which influences virulence in other fungi. The Δace2 mutant had dysmorphic conidiophores, reduced conidia production, and abnormal conidial cell wall architecture. This mutant produced an orange pigment when grown on solid media, although its conidia had normal pigmentation. Conidia of the Δace2 mutant were larger and had accelerated germination. The resulting germlings were resistant to hydrogen peroxide, but not other stressors. Non-neutropenic mice that were immunosuppressed with cortisone acetate and infected with the Δace2 mutant had accelerated mortality, greater pulmonary fungal burden, and increased pulmonary inflammatory responses compared to mice infected with the wild-type or Δace2∷ace2 complemented strains. The Δace2 mutant had reduced ppoC, ecm33, and ags3 mRNA expression. It is known that A. fumigatus mutants with absent or reduced expression of these genes have increased virulence in mice, as well as other phenotypic similarities to the Δace2 mutant. Therefore, reduced expression of these genes likely contributes to the increased virulence of the Δace2 mutant. PMID:19220748

  14. Pistacia lentiscus Oleoresin: Virtual Screening and Identification of Masticadienonic and Isomasticadienonic Acids as Inhibitors of 11β-Hydroxysteroid Dehydrogenase 1.

    Science.gov (United States)

    Vuorinen, Anna; Seibert, Julia; Papageorgiou, Vassilios P; Rollinger, Judith M; Odermatt, Alex; Schuster, Daniela; Assimopoulou, Andreana N

    2015-04-01

    In traditional medicine, the oleoresinous gum of Pistacia lentiscus var. chia, so-called mastic gum, has been used to treat multiple conditions such as coughs, sore throats, eczema, dyslipidemia, and diabetes. Mastic gum is rich in triterpenes, which have been postulated to exert antidiabetic effects and improve lipid metabolism. In fact, there is evidence of oleanonic acid, a constituent of mastic gum, acting as a peroxisome proliferator-activated receptor γ agonist, and mastic gum being antidiabetic in mice in vivo. Despite these findings, the exact antidiabetic mechanism of mastic gum remains unknown. Glucocorticoids play a key role in regulating glucose and fatty acid metabolism, and inhibition of 11β-hydroxysteroid dehydrogenase 1 that converts inactive cortisone to active cortisol has been proposed as a promising approach to combat metabolic disturbances including diabetes. In this study, a pharmacophore-based virtual screening was applied to filter a natural product database for possible 11β-hydroxysteroid dehydrogenase 1 inhibitors. The hit list analysis was especially focused on the triterpenoids present in Pistacia species. Multiple triterpenoids, such as masticadienonic acid and isomasticadienonic acid, main constituents of mastic gum, were identified. Indeed, masticadienonic acid and isomasticadienonic acid selectively inhibited 11β-hydroxysteroid dehydrogenase 1 over 11β-hydroxysteroid dehydrogenase 2 at low micromolar concentrations. These findings suggest that inhibition of 11β-hydroxysteroid dehydrogenase 1 contributes to the antidiabetic activity of mastic gum.

  15. Preliminary data on Pemphigus vulgaris treatment by a proteomics-defined peptide: a case report

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    Mittelman Abraham

    2006-10-01

    Full Text Available Abstract Background Although described by Hippocrates in 400 B.C., pemphigus disease still needs a safe therapeutical approach, given that the currently used therapies (i.e. corticosteroids and immunosuppressive drugs often provoke collateral effects. Here we present preliminary data on the possible use of a proteomics derived desmoglein peptide which appears promising in halting disease progression without adverse effects. Methods The low-similarity Dsg349–60REWVKFAKPCRE peptide was topically applied for 1 wk onto a lesion in a patient with a late-stage Pemphigus vulgaris (PV complicated by diabetes and cataract disease. The peptide was applied as an adjuvant in combination with the standard corticosteroid-based immunosuppressive treatment. Results After 1 wk, the treated PV eroded lesion appeared dimensionally reduced and with an increased rate of re-epithelization when compared to adjacent non-treated lesions. Short-term benefits were: decrease of anti-Dsg antibody titer and reduction of the corticosteroid dosage. Long-term benefits: after two years following the unique 1-wk topical treatment, the decrease of anti-Dsg antibody titer persists. The patient is still at the low cortisone dosage. Adverse effects: no adverse effect could be monitored. Conclusion With the limits inherent to any preliminary study, this case report indicates that topical treatment with Dsg349–60REWVKFAKPCRE peptide may represent a feasible first step in the search for a simple, effective and safe treatment of PV.

  16. A multi-modal treatment approach for the shoulder: A 4 patient case series

    Directory of Open Access Journals (Sweden)

    Pollard Henry

    2005-09-01

    Full Text Available Abstract Background This paper describes the clinical management of four cases of shoulder impingement syndrome using a conservative multimodal treatment approach. Clinical Features Four patients presented to a chiropractic clinic with chronic shoulder pain, tenderness in the shoulder region and a limited range of motion with pain and catching. After physical and orthopaedic examination a clinical diagnosis of shoulder impingement syndrome was reached. The four patients were admitted to a multi-modal treatment protocol including soft tissue therapy (ischaemic pressure and cross-friction massage, 7 minutes of phonophoresis (driving of medication into tissue with ultrasound with 1% cortisone cream, diversified spinal and peripheral joint manipulation and rotator cuff and shoulder girdle muscle exercises. The outcome measures for the study were subjective/objective visual analogue pain scales (VAS, range of motion (goniometer and return to normal daily, work and sporting activities. All four subjects at the end of the treatment protocol were symptom free with all outcome measures being normal. At 1 month follow up all patients continued to be symptom free with full range of motion and complete return to normal daily activities. Conclusion This case series demonstrates the potential benefit of a multimodal chiropractic protocol in resolving symptoms associated with a suspected clinical diagnosis of shoulder impingement syndrome.

  17. Successful Treatment of a Severe Case of Fournier's Gangrene Complicating a Perianal Abscess

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    Ioannis Papaconstantinou

    2011-01-01

    Full Text Available A 67-year-old male patient with diabetes mellitus and nephritic syndrome under cortisone treatment was admitted to our hospital with fever and severe perianal pain. Upon physical examination, a perianal abscess was identified. Furthermore, the scrotum was gangrenous with extensive cellulitis of the perineum and left lower abdominal wall. Crepitations between the skin and fascia were palpable. A diagnosis of Fournier's gangrene was made. He was treated with immediate extensive surgical debridement under general anesthesia. The patient received broad-spectrum antibiotics, and repeated extensive debridements were performed until healthy granulation was present in the wound. Due to the fact that his left testicle was severely exposed, it was transpositioned into a subcutaneous pocket in the inner side of the left thigh. He was finally discharged on the 57th postoperative day. Fournier's gangrene is characterized by high mortality rates, ranging from 15% to 50% and is an acute surgical emergency. The mainstay of treatment should be open drainage and early aggressive surgical debridement of all necrotic tissue, followed by broad-spectrum antibiotics therapy.

  18. Catarata subcapsular posterior em pacientes com pênfigo e penfigóide tratados com corticoterapia oral Posterior subcapsular cataract in patients with pemphigus and pemphigoid using oral corticosteroid

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    Viviane Reggiani

    2004-10-01

    bullous diseases using a corticosteroid were followed-up from 1987 to 1997 at the Bullous Dermatosis Outpatient Care Unit of the Department of Dermatology, UNIFESP - EPM. The patients were regularly submitted to ophthalmologic evaluation in search for cortisone cataract. This evaluation was carried out at the beginning of the treatment and regularly during the use of the corticosteroid. RESULTS: From 1987 to 1997, the incidence of posterior subcapsular cataract as a side effect of oral corticosteroid was 28.57% in these patients. CONCLUSIONS: 1 among 49 patients, 14 (28.57% presented with cortisone cataract. 2 the period of time of prednisone use up to the appearance of cataract varied from eight months to nine years and three months (average 45.71 months. 3 the maximum dose of oral corticosteroid required for the management of the clinical picture ranged from 60 to 120 mg daily (average of 78.57 mg daily.

  19. 六味地黄苷糖对悬吊应激小鼠生殖内分泌及免疫系统的影响%LW-AFC Improved or Restored the Disturbance of Reproductive Endocrine and Immune Function in Stress-Loaded Mice

    Institute of Scientific and Technical Information of China (English)

    谢兴振; 迟晓丽; 周文霞; 马渊; 张永祥

    2011-01-01

    目前尚无有效可靠的抗应激药物.传统的补益中药六味地黄汤(LW)对多种类型应激所致内分泌和免疫平衡失调具有明显调节作用,但目前已上市的LW成药缺乏可靠的质量控制方法,其临床疗效的可靠程度难以估测.本课题组在前期研究中以免疫和内分泌活性评价为导向,从LW中追踪分离并组成了质量可控且安全性好的六味地黄苷糖(LW-AFC).本文观察了悬吊应激雌性小鼠生殖内分泌及免疫系统的变化及LW-AFC的影响.结果表明,悬吊应激小鼠皮质酮升高,动情期缩短、动情间期延长,垂体LH下降,动情间期血清E2升高;脾细胞培养上清IgG含量明显降低;口服LW-AFC能显著降低血清皮质酮,升高垂体LH,且LW-AFC能明显降低动情间期血清E2,并能明显增强脾细胞IgG分泌能力.这提示,悬吊应激可导致雌性小鼠生殖内分泌功能紊乱以及免疫功能下降,口服LW-AFC具有明显调节作用,对应激所致生殖内分泌功能紊乱以及免疫功能下降具有潜在防治作用.%There are no effective and reliable anti-stress drugs. Traditional Chinese Medicine Liu Wei Di Huang Decoction (LW) can interfere with the various types of stress-induced endocrine and immune imbalance. However, traditional LW lacks reliable quality control methods, and the reliability of its clinical efficacy is difficult to estimate. In our previous study we evaluated the immune and endocrine activity of different parts from LW separation, and then formed LW-AFC which has satisfactory quality control, security and activity. In this paper, we observe the impact of LW-AFC on the reproductive endocrine and immune system of suspension-stressed female mouse. The results show that the stress increased the serum cortisone, reduced estrus cycle, prolonged diestrus, decreased the pituitary LH, but increased serum E2 on diestrus cycle, and IgG in spleen cell culture supernatant was significantly reduced after suspension

  20. 颅脑创伤后尿崩症合并脑性盐耗综合征%Combined central diabetes insipidus and cerebral salt wasting syndrome after traumatic brain injury

    Institute of Scientific and Technical Information of China (English)

    吴雪海; 高亮; 胡锦; 吴惺; 郎黎琴; 金毅; 毛颖; 周良辅

    2011-01-01

    目的 探讨如何正确认识、早期及时诊断和准确治疗尿崩症合并脑性盐耗综合征,以提高救治成功率.方法 回顾性分析6例尿崩症合并脑性盐耗综合征的临床特点:尿量特别异常增多、高脑利钠肽水平和显著尿钠排泄增加是其最显著特征;尿比重、血钠水平和血浆渗透压可以正常;尿量增多单纯加压素疗效不佳,而加用醋酸可的松治疗有效.结果 6例患者及时正确诊断为尿崩症合并脑性盐耗综合征,但其中1例患者因为血钠上升过快出现脑桥脱髓鞘病变,最终植物状态;1例患者因脑疝、多脏衰而死亡;其余4例患者治愈出院.结论 根据尿崩症合并脑性盐耗综合征的临床特点本文提出其参考诊断标准,及时诊断和正确治疗是成功救治的关键.%Objective To discuss the diagnosis coexistence of central diabetes insipidus and cerebral salt wasting syndrome promptly and treat properly.Method Six patients who suffered central diabetes insipidus combined cerebral salt wasting syndrome were analyzed retrospectively.Its characteristics was massive polyuria which can not be controlled by vasopressin alone,but can be controlled by both vasopresin and cortisone acetate.Sodium chloride saline were mainly used to make up for the loss of water and salt.Other charactefistcs were including low CVP,high Pro - BNP,high 24 h urine sodium evacuation with normal serum sodium level,higher osmolarity in urine than in serum which was at normal level,and usually normal urine specific gravity.Results One died and one became vegetative state,other four patients discharged with Glasgow Coma Scale 15.Conclusions Monitoring of water and sodium metabolism systemically were critical to diagnose the concurrent DI and CSW.Slow sodium chloride saline supplement,cortisone acetate and desmopressin were the keys to deal with concurrent DI and CSW.With exact diagnosis and treatment promptly,favourable outcome can be achieved.

  1. Drug therapy for ulcerative colitis

    Institute of Scientific and Technical Information of China (English)

    Chang-Tai Xu; Shu-Yong Meng; Bo-Rong Pan

    2004-01-01

    Ulcerative colitis (UC) is an inflammatory destructive disease of the large intestine occurred usually in the rectum and lower part of the colon as well as the entire colon. Drug therapy is not the only choice for UC treatment and medical management should be as a comprehensive whole.Azulfidine, Asacol, Pentasa, Dipentum, and Rowasa all contain 5-aminosalicylic acid (5-ASA), which is the topical anti-inflammatory ingredient. Pentasa is more commonly used in treating Crohn's ileitis because Pentasa capsules release more 5-ASA into the small intestine than Asacol tablets. Pentasa can also be used for treating mild to moderate UC. Rowasa enemas are safe and effective in treating ulcerative proctitis and proctosigmoiditis. The sulfafree 5-ASA agents (Asacol, Pentasa, Dipentum and Rowasa) have fewer side effects than sulfa-containing Azulfidine. In UC patients with moderate to severe disease and in patients who failed to respond to 5-ASA compounds,systemic (oral) corticosteroids should be used. Systemic corticosteroids (prednisone, prednisolone, cortisone, etc.)are potent and fast-acting drugs for treating UC, Crohn's ileitis and ileocolitis. Systemic corticosteroids are not effective in maintaining remission in patients with UC.Serious side effects can result from prolonged corticosteroid treatment. To minimize side effects, corticosteroids should be gradually reduced as soon as the disease remission is achieved. In patients with corticosteroid-dependent or unresponsive to corticosteroid treatment, surgery or immunomodulator is considered. Immunomodulators used for treating severe UC include azathioprine/6-MP,methotrexate, and cyclosporine. Integrated traditional Chinese and Western medicine is safe and effective in maintaining remission in patients with UC.

  2. Effects of DHEA on metabolic and endocrine functions of adipose tissue.

    Science.gov (United States)

    Karbowska, Joanna; Kochan, Zdzislaw

    2013-08-01

    Dehydroepiandrosterone (DHEA) and its sulfate ester, DHEAS, are the major circulating adrenal steroids and serve as substrates for sex hormone biosynthesis. DHEA is effectively taken up by adipose tissue, where the concentrations of free DHEA are four to ten times higher than those found in the circulation. DHEA reduces adipose tissue mass and inhibits the proliferation and differentiation of adipocytes; it may also protect against obesity by lowering the activity of stearoyl-CoA desaturase 1 in fat cells. Recent studies demonstrate that DHEA stimulates triacylglycerol hydrolysis in adipose tissue by increasing the expression and activity of adipose triglyceride lipase and hormone-sensitive lipase, the key enzymes of lipolysis. DHEA has been shown to modulate insulin signaling pathways, enhance glucose uptake in adipocytes, and increase insulin sensitivity in patients with DHEA deficiency or abnormal glucose tolerance. Additionally, by suppressing the activity of 11β-hydroxysteroid dehydrogenase 1 in adipocytes, DHEA may promote intra-adipose inactivation of cortisol to cortisone. Several studies have demonstrated that DHEA may also regulate the expression and secretion of adipokines such as leptin, adiponectin, and resistin. The effects of DHEA on adipokine expression in adipose tissue are depot-specific, with visceral fat being the most responsive. The mechanisms underlying DHEA actions in adipose tissue are still unclear; however, they involve nuclear receptors such as androgen receptor and peroxisome proliferator-activated receptors γ and α. Because clinical trials investigating the effects of DHEA failed to yield consistent results, further studies are needed to clarify the role of DHEA in the regulation of human adipose tissue physiology.

  3. 11β-hydroxysteroid dehydrogenase 1 specific inhibitor increased dermal collagen content and promotes fibroblast proliferation.

    Directory of Open Access Journals (Sweden)

    Mika Terao

    Full Text Available Glucocorticoids (GCs are one of the most effective anti-inflammatory drugs for treating acute and chronic inflammatory diseases. However, several studies have shown that GCs alter collagen metabolism in the skin and induce skin atrophy. Cortisol is the endogenous GC that is released in response to various stressors. Over the last decade, extraadrenal cortisol production in various tissues has been reported. Skin also synthesizes cortisol through a de novo pathway and through an activating enzyme. 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1 is the enzyme that catalyzes the conversion of hormonally inactive cortisone to active cortisol in cells. We previously found that 11β-HSD1 negatively regulates proliferation of keratinocytes. To determine the function of 11β-HSD1 in dermal fibroblasts and collagen metabolism, the effect of a selective 11β-HSD1 inhibitor was studied in mouse tissues and dermal fibroblasts. The expression of 11β-HSD1 increased with age in mouse skin. Subcutaneous injection of a selective 11β-HSD1 inhibitor increased dermal thickness and collagen content in the mouse skin. In vitro, proliferation of dermal fibroblasts derived from 11β-HSD1 null mice (Hsd11b1(-/- mice was significantly increased compared with fibroblasts from wild-type mice. However, in vivo, dermal thickness of Hsd11b1(-/- mice was not altered in 3-month-old and 1-year-old mouse skin compared with wild-type mouse skin. These in vivo findings suggest the presence of compensatory mechanisms in Hsd11b1(-/- mice. Our findings suggest that 11β-HSD1 inhibition may reverse the decreased collagen content observed in intrinsically and extrinsically aged skin and in skin atrophy that is induced by GC treatment.

  4. Pathway analysis reveals common pro-survival mechanisms of metyrapone and carbenoxolone after traumatic brain injury.

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    Helen L Hellmich

    Full Text Available Developing new pharmacotherapies for traumatic brain injury (TBI requires elucidation of the neuroprotective mechanisms of many structurally and functionally diverse compounds. To test our hypothesis that diverse neuroprotective drugs similarly affect common gene targets after TBI, we compared the effects of two drugs, metyrapone (MT and carbenoxolone (CB, which, though used clinically for noncognitive conditions, improved learning and memory in rats and humans. Although structurally different, both MT and CB inhibit a common molecular target, 11β hydroxysteroid dehydrogenase type 1, which converts inactive cortisone to cortisol, thereby effectively reducing glucocorticoid levels. We examined injury-induced signaling pathways to determine how the effects of these two compounds correlate with pro-survival effects in surviving neurons of the injured rat hippocampus. We found that treatment of TBI rats with MT or CB acutely induced in hippocampal neurons transcriptional profiles that were remarkably similar (i.e., a coordinated attenuation of gene expression across multiple injury-induced cell signaling networks. We also found, to a lesser extent, a coordinated increase in cell survival signals. Analysis of injury-induced gene expression altered by MT and CB provided additional insight into the protective effects of each. Both drugs attenuated expression of genes in the apoptosis, death receptor and stress signaling pathways, as well as multiple genes in the oxidative phosphorylation pathway such as subunits of NADH dehydrogenase (Complex1, cytochrome c oxidase (Complex IV and ATP synthase (Complex V. This suggests an overall inhibition of mitochondrial function. Complex 1 is the primary source of reactive oxygen species in the mitochondrial oxidative phosphorylation pathway, thus linking the protective effects of these drugs to a reduction in oxidative stress. The net effect of the drug-induced transcriptional changes observed here indicates that

  5. Modulation of lymphopoiesis

    Energy Technology Data Exchange (ETDEWEB)

    Rosse, C.

    1990-01-01

    Ongoing experiments contribute to the four specific aims in our current 3-year project period studying lymphopoiesis using CE mammary adenocarcinoma (CE maca) mice. Specific Aim 1: Function of Bone Marrow Stroma in CE Maca Bearing Mice. We have concluded that bone marrow stromal cells from tumor bearing animals are as effective as bone marrow stromal cells from normal animals at supporting B lymphopoiesis in culture. If stromal cell disfunction occurs in tumor bearing animals, the effect is not long lasting. Specific Aim 2: Factors Elaborated by CE Maca. Conditioned medium from CE maca cultures induces bone resorbing activity in bone organ cultures. We have identified a 32 kDa protein that meets the criteria for an osteoclast specific growth factor in this medium. However, we have also found that even though an osteoclast specific growth factor exists, a growth factor whose primary targets are granulocyte precursors will also stimulate osteoclast activity. Specific Aim 3: In Vitro Systems for Investigating Modulation of NK Lymphopoiesis by CE Maca. CE maca is shown to inhibit NK all production as well as B all production. In the course of the these experiments, we have established conditions for enriching NK precursors and have established a prototype long term bone marrow culture system which shows NK cell production. Specific Aim 4: Relationship Between Myclogenic and Intrathymic T Cell Precursors. There is evidence for a stream of T all maturation in both host (or intrathymic) cells and non-host (both hematogenous and intrathymic) cells. If thymic atrophy is induced by cortisone (a depopulation equivalent to that caused by 1000 rad) our data conclusively show thymic recovery is effected almost exclusively by intrathymic cells. This assigns a much greater importance to intrathymic T all progenitors in the maintenance of T cell production in the thymus than has been hitherto recognized. (MHB)

  6. Immunotherapy of murine leukemia. Efficacy of passive serum therapy of Friend leukemia virus-induced disease in immunocompromised mice

    Energy Technology Data Exchange (ETDEWEB)

    Genovesi, E.V.; Livnat, D.; Collins, J.J.

    1983-02-01

    Previous studies have demonstrated that the passive therapy of Friend murine leukemia virus (F-MuLV)-induced disease with chimpanzee anti-F-MuLV serum is accompanied by the development of host antiviral humoral and cellular immunity, the latter measurable in adoptive transfer protocols and by the ability of serum-protected mice to resist virus rechallenge. The present study was designed to further examine the contribution of various compartments of the host immune system to serum therapy itself, as well as to the acquired antiviral immunity that develops in serum-protected mice, through the use of naturally immunocompromised animals (e.g., nude athymic mice and natural killer (NK)-deficient beige mutant mice) or mice treated with immunoabrogating agents such as sublethal irradiation, cyclophosphamide (Cytoxan (Cy)), cortisone, and /sup 89/Sr. The studies in nude mice indicate that while mature T-cells are not needed for effective serum therapy, they do appear to be necessary for the long-term resistance of serum-protected mice to virus rechallenge and for the generation of the cell population(s) responsible for adoptive transfer of antiviral immunity. Furthermore, this acquired resistance is not due to virus neutralization by serum antibodies since antibody-negative, Cy-treated, serum-protected mice still reject the secondary virus infection. Lastly, while the immunocompromise systems examined did effect various host antiviral immune responses, none of them, including the NK-deficient beige mutation, significantly diminished the efficacy of the passive serum therapy of F-MuLV-induced disease.

  7. Decreased 11β-Hydroxysteroid Dehydrogenase 1 Level and Activity in Murine Pancreatic Islets Caused by Insulin-Like Growth Factor I Overexpression.

    Directory of Open Access Journals (Sweden)

    Subrata Chowdhury

    Full Text Available We have reported a high expression of IGF-I in pancreatic islet β-cells of transgenic mice under the metallothionein promoter. cDNA microarray analysis of the islets revealed that the expression of 82 genes was significantly altered compared to wild-type mice. Of these, 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1, which is responsible for the conversion of inert cortisone (11-dehydrocorticosterone, DHC in rodents to active cortisol (corticosterone in the liver and adipose tissues, has not been identified previously as an IGF-I target in pancreatic islets. We characterized the changes in its protein level, enzyme activity and glucose-stimulated insulin secretion. In freshly isolated islets, the level of 11β-HSD1 protein was significantly lower in MT-IGF mice. Using dual-labeled immunofluorescence, 11β-HSD1 was observed exclusively in glucagon-producing, islet α-cells but at a lower level in transgenic vs. wild-type animals. MT-IGF islets also exhibited reduced enzymatic activities. Dexamethasone (DEX and DHC inhibited glucose-stimulated insulin secretion from freshly isolated islets of wild-type mice. In the islets of MT-IGF mice, 48-h pre-incubation of DEX caused a significant decrease in insulin release, while the effect of DHC was largely blunted consistent with diminished 11β-HSD1 activity. In order to establish the function of intracrine glucocorticoids, we overexpressed 11β-HSD1 cDNA in MIN6 insulinoma cells, which together with DHC caused apoptosis and a significant decrease in proliferation. Both effects were abolished with the treatment of an 11β-HSD1 inhibitor. Our results demonstrate an inhibitory effect of IGF-I on 11β-HSD1 expression and activity within the pancreatic islets, which may mediate part of the IGF-I effects on cell proliferation, survival and insulin secretion.

  8. Doctor Guillermo García López (1905-1956, gran diabetólogo cubano Doctor Guillermo García López (1905-1956, a great cuban diabetologist

    Directory of Open Access Journals (Sweden)

    Dagoberto Álvarez Aldana

    2004-08-01

    Full Text Available Con esta breve semblanza pretendemos esbozar algunos datos biográficos del profesor Guillermo García López (1905-1956 notable, pero casi desconocido galeno, y resaltar su labor profesional en el campo asistencial, docente y científico en nuestro país, que lo avalan como uno de los más importantes diabetólogos cubanos. Consultamos la bibliografía médica de la época, archivos, expedientes y otras fuentes para la realización de esta investigación. El doctor Guillermo García López aportó más de 50 contribuciones médicas, las cuales se publicaron en prestigiosas revistas dentro y fuera de Cuba. Sobresalió por sus estudios sobre la diabetes infantil, como se le llamaba en aquellos años, las mejores combinaciones de insulinitas, el uso de insulina NPH, las hormonas adrenocorticotrópicas (ACTH y la cortisona, entre otros.With this brief biographical profile we intend to outline some data on professor Guillermo García López (1905-1956, an outstanding but almost unknown doctor, and to highlight his professional work in the assistance, teaching and scientific field in our country, that makes him one of the most important Cuban diabetologists. We consulted the medical bibliography of that time, archives, records and other sources as part of this research. Doctor Guillermo García López made more than 50 medical contributions that were published in prestigious journals in Cuba and abroad. He stood out for his studies on infantile diabetes, as it was called in those years, the best insulin combinations, the use of NPH insulin, adrenocorticotropic hormones (ACTH and cortisone, among others.

  9. Selection of restriction specificities of virus-specific cytotoxic T cells in the thymus: no evidence for a crucial role of antigen-presenting cells

    Energy Technology Data Exchange (ETDEWEB)

    Zinkernagel, R.M.

    1982-12-01

    The proposal was tested that (P1 X P2) F1 leads to P1 irradiation bone marrow chimeras expressed predominantly P1-restricted T cells because donor derived stem cells were exposed to recipient derived antigen-presenting cells in the thymus. Because P1 recipient-derived antigen-presenting cells are replaced only slowly after 6-8 wk by (P1 X P2) donor-derived antigen-presenting cells in the thymus and because replenished pools of mature T cells may by then prevent substantial numbers of P2-restricted T cells to be generated, a large portion of thymus cells and mature T cells were eliminated using the following treatments of 12-20-wk-old (P1 X P2) F1 leads to P1 irradiation bone marrow chimeras: (a) cortisone plus antilymphocyte serum, (b) Cytoxan, (c) three doses of sublethal irradiation (300 rad) 2d apart, and (d) lethal irradiation (850 rad) and reconstitution with T cell-depleted (P1 X P2) F1 stem cells. 12-20 wk after this second treatment, (P1 X P2) leads to P1 chimeras were infected with vaccinia-virus. Virus-specific cytotoxic T cell reactivity was expressed by chimeric T cells of (P1 X P(2) F1 origin and was restricted predominantly to P1. Virus-specific cytotoxic T cells, therefore, do not seem to be selected to measurable extent by the immigrating donor-derived antigen-presenting cells in the thymus; their selection depends apparently from the recipient-derived radioresistant thymus cells.

  10. Depletion of (/sup 3/H)methyltrienolone cytosol binding in glucocorticoid-induced muscle atrophy (42001)

    Energy Technology Data Exchange (ETDEWEB)

    Kurowski, T.T.; Capaccio, J.A.; Chatterton, R.T. Jr.; Hickson, R.C.

    1985-01-01

    The present study was undertaken to determine cytosol binding properties of (/sup 3/H)methyltrienolone, a synthetic androgen, in comparison with (/sup 3/)dexamethasone, a synthetic glucocorticoid, under conditions of glucocorticoid excess in skeletal muscle. Male hypophysectomized rats received either seven daily subcutaneous injections of cortisone acetate (CA) (100 mg x kg/sup -1/ body wt) or the vehicle, 1% carboxymethyl cellulose. Following treatment, both (/sup 3/H)dexamethansone and (/sup 3/H)methyltrienolone-receptor concentrations were decreased from those in vehicle-treated rats by more than 90 and 80%, respectively, in CA-treated animals. Scatchard analysis of (/sup 3/H)methyltrienolone binding in muscles of vehicle-treated animals became nonlinear at high concentrations of labeled ligand and were reanalyzed by a two-component binding model. The lower affinity, higher capacity component, which was attributed to binding of methyltrienolone to a dexamethasone component, which was attributed to binding of methyltrienolone to a dexamethasone component, disappeared in muscles of CA-treated rats and Scatchard plots were linear. Receptor concentrations of the higher affinity lower capacity methyltrienolone component were similar in muscles of vehicle-treated and CA-treated groups. From competition studies, the high relative specificities of glucocorticoids for (/sup 3/H)methyltrienolone binding in muscles of vehicle-treated animals were markedly reduced by CA treatment. In addition, the binding specificity data also showed strong competition by progesterone and methyltrienolone for (/sup 3/H)dexamethasone binding and estradiol-17..beta.. for (/sup 3/H)methyltrienolone binding.

  11. Epidemiological aspects of centipede (Scolopendromorphae: Chilopoda bites registered in Greater S. Paulo, SP, Brazil

    Directory of Open Access Journals (Sweden)

    Knysak Irene

    1998-01-01

    Full Text Available INTRODUCTION: The lack of basic knowledge on venomous arthropods and the benignity of the clinical manifestations contribute to the centipede bite victims' not being taken to a treatment reference center, leading to underestimation of the number of cases and minimizing the possibility of a broader epidemiological view. An inventory of the centipede bite occurrences in Greater S. Paulo, Brazil, and the therapeutic methods employed, by the main Brazilian medical center for the notification of poisoning by venomous animals, is presented. METHOD: All patient cards of the period 1980-1989 have been checked as to place, month and time of occurrence; sex, age, affected part of the body, signs and symptoms have been observed, as well as the therapeutic methods employed. The centipedes that caused the accidents were identified at the Arthropods Laboratory. RESULTS: It was registered 216 accidents, with a 69% predominance of the Greater S. Paulo and in only 63% of the cases (136 was the agent brought in by the victim for identification. The genera most frequently represented were Cryptops (58%, Otostigmus (33% and Scolopendra (4%. Of the 136 cases, 87% showed erythema, edema, hemorrhage, burns, cephalalgia, and intense pain. There was a predominance of accidents in the warm rainy season, in the morning and for females between 21 and 60 years of age. Hands and feet were the parts of the body most affected. The benign evolution of the clinical picture (54% made therapeutical treatment unnecessary. Only the victims of Scolopendra and Otostigmus (46% were medicated with anesthetics (51%, analgesics (25%, antihistamines and cortisone (24%. CONCLUSION: The reproductive period of the centipedes, associated with their sinanthropic habits, contributes to the greater incidence of accidents in urban areas in the warm rainy season. Only patients bitten by Scolopendra and Otostigmus require therapeutical treatment.

  12. Virtual screening as a strategy for the identification of xenobiotics disrupting corticosteroid action.

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    Lyubomir G Nashev

    Full Text Available BACKGROUND: Impaired corticosteroid action caused by genetic and environmental influence, including exposure to hazardous xenobiotics, contributes to the development and progression of metabolic diseases, cardiovascular complications and immune disorders. Novel strategies are thus needed for identifying xenobiotics that interfere with corticosteroid homeostasis. 11β-hydroxysteroid dehydrogenase 2 (11β-HSD2 and mineralocorticoid receptors (MR are major regulators of corticosteroid action. 11β-HSD2 converts the active glucocorticoid cortisol to the inactive cortisone and protects MR from activation by glucocorticoids. 11β-HSD2 has also an essential role in the placenta to protect the fetus from high maternal cortisol concentrations. METHODS AND PRINCIPAL FINDINGS: We employed a previously constructed 3D-structural library of chemicals with proven and suspected endocrine disrupting effects for virtual screening using a chemical feature-based 11β-HSD pharmacophore. We tested several in silico predicted chemicals in a 11β-HSD2 bioassay. The identified antibiotic lasalocid and the silane-coupling agent AB110873 were found to concentration-dependently inhibit 11β-HSD2. Moreover, the silane AB110873 was shown to activate MR and stimulate mitochondrial ROS generation and the production of the proinflammatory cytokine interleukin-6 (IL-6. Finally, we constructed a MR pharmacophore, which successfully identified the silane AB110873. CONCLUSIONS: Screening of virtual chemical structure libraries can facilitate the identification of xenobiotics inhibiting 11β-HSD2 and/or activating MR. Lasalocid and AB110873 belong to new classes of 11β-HSD2 inhibitors. The silane AB110873 represents to the best of our knowledge the first industrial chemical shown to activate MR. Furthermore, the MR pharmacophore can now be used for future screening purposes.

  13. Epidemiological aspects of centipede (Scolopendromorphae: Chilopoda bites registered in Greater S. Paulo, SP, Brazil

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    Irene Knysak

    1998-12-01

    Full Text Available INTRODUCTION: The lack of basic knowledge on venomous arthropods and the benignity of the clinical manifestations contribute to the centipede bite victims' not being taken to a treatment reference center, leading to underestimation of the number of cases and minimizing the possibility of a broader epidemiological view. An inventory of the centipede bite occurrences in Greater S. Paulo, Brazil, and the therapeutic methods employed, by the main Brazilian medical center for the notification of poisoning by venomous animals, is presented. METHOD: All patient cards of the period 1980-1989 have been checked as to place, month and time of occurrence; sex, age, affected part of the body, signs and symptoms have been observed, as well as the therapeutic methods employed. The centipedes that caused the accidents were identified at the Arthropods Laboratory. RESULTS: It was registered 216 accidents, with a 69% predominance of the Greater S. Paulo and in only 63% of the cases (136 was the agent brought in by the victim for identification. The genera most frequently represented were Cryptops (58%, Otostigmus (33% and Scolopendra (4%. Of the 136 cases, 87% showed erythema, edema, hemorrhage, burns, cephalalgia, and intense pain. There was a predominance of accidents in the warm rainy season, in the morning and for females between 21 and 60 years of age. Hands and feet were the parts of the body most affected. The benign evolution of the clinical picture (54% made therapeutical treatment unnecessary. Only the victims of Scolopendra and Otostigmus (46% were medicated with anesthetics (51%, analgesics (25%, antihistamines and cortisone (24%. CONCLUSION: The reproductive period of the centipedes, associated with their sinanthropic habits, contributes to the greater incidence of accidents in urban areas in the warm rainy season. Only patients bitten by Scolopendra and Otostigmus require therapeutical treatment.

  14. Anti-inflammatory effect of a selective 11β-hydroxysteroid dehydrogenase type 1 inhibitor via the stimulation of heme oxygenase-1 in LPS-activated mice and J774.1 murine macrophages

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    Sung Bum Park

    2016-08-01

    Full Text Available 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1 converts inactive cortisone to the active cortisol. 11β-HSD1 may be involved in the resolution of inflammation. In the present study, we investigate the anti-inflammatory effects of 2-(3-benzoyl-4-hydroxy-1,1-dioxo-2H-1,2-benzothiazine-2-yl-1-phenylethanone (KR-66344, a selective 11β-HSD1 inhibitor, in lipopolysaccharide (LPS-activated C57BL/6J mice and macrophages. LPS increased 11β-HSD1 activity and expression in macrophages, which was inhibited by KR-66344. In addition, KR-66344 increased survival rate in LPS treated C57BL/6J mice. HO-1 mRNA expression level was increased by KR-66344, and this effect was reversed by the HO competitive inhibitor, ZnPP, in macrophages. Moreover, ZnPP reversed the suppression of ROS formation and cell death induced by KR-66344. ZnPP also suppressed animal survival rate in LPS plus KR-66344 treated C57BL/6J mice. In the spleen of LPS-treated mice, KR-66344 prevented cell death via suppression of inflammation, followed by inhibition of ROS, iNOS and COX-2 expression. Furthermore, LPS increased NFκB-p65 and MAPK phosphorylation, and these effects were abolished by pretreatment with KR-66344. Taken together, KR-66344 protects against LPS-induced animal death and spleen injury by inhibition of inflammation via induction of HO-1 and inhibition of 11β-HSD1 activity. Thus, we concluded that the selective 11β-HSD1 inhibitor may provide a novel strategy in the prevention/treatment of inflammatory disorders in patients.

  15. A semi-physiologically based pharmacokinetic pharmacodynamic model for glycyrrhizin-induced pseudoaldosteronism and prediction of the dose limit causing hypokalemia in a virtual elderly population.

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    Ruijuan Xu

    Full Text Available Glycyrrhizin (GL is a widely used food additive which can cause severe pseudoaldosteronism at high doses or after a long period of consumption. The aim of the present study was to develop a physiologically based pharmacokinetic (PBPK pharmacodynamic (PD model for GL-induced pseudoaldosteronism to improve the safe use of GL. Since the major metabolite of GL, glycyrrhetic acid (GA, is largely responsible for pseudoaldosteronism via inhibition of the kidney enzyme 11β-hydroxysteroiddehydrogenase 2 (11β-HSD 2, a semi-PBPK model was first developed in rat to predict the systemic pharmacokinetics of and the kidney exposure to GA. A human PBPK model was then developed using parameters either from the rat model or from in vitro studies in combination with essential scaling factors. Kidney exposure to GA was further linked to an Imax model in the 11β-HSD 2 module of the PD model to predict the urinary excretion of cortisol and cortisone. Subsequently, activation of the mineralocorticoid receptor in the renin-angiotensin-aldosterone-electrolyte system was associated with an increased cortisol level. Experimental data for various scenarios were used to optimize and validate the model which was finally able to predict the plasma levels of angiotensin II, aldosterone, potassium and sodium. The Monte Carlo method was applied to predict the probability distribution of the individual dose limits of GL causing pseudoaldosteronism in the elderly according to the distribution of sensitivity factors using serum potassium as an indicator. The critical value of the dose limit was found to be 101 mg with a probability of 3.07%.

  16. Plantar fasciitis – to jab or to support? A systematic review of the current best evidence

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    Uden H

    2011-05-01

    , corticosteroid injections may have side effects (especially pain as a result of the injection, which may limit its acceptability.Keywords: plantar fasciitis, heel pain, orthotics, orthoses, cortisone injection, corticosteroid injection

  17. Longitudinal analyses of the steroid metabolome in obese PCOS girls with weight loss

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    Thomas Reinehr

    2017-05-01

    Full Text Available Objective: The underlying mechanisms of polycystic ovarian syndrome (PCOS are not fully understood yet. The aim of the study was to get functional insights into the regulation of steroid hormones in PCOS by steroid metabolomics. Design: This is a longitudinal study of changes of steroid hormones in 40 obese girls aged 13–16 years (50% with PCOS participating in a 1-year lifestyle intervention. Girls with and without PCOS were matched to age, BMI and change of weight status. Methods: We measured progesterone, 17-hydroxyprogesterone, 17-hydroxyprogenolon, 11-deoxycorticosterone, 21-deoxycorticosterone, deoxycorticosterone, corticosterone, 11-deoxycortisol, cortisol, cortisone, androstenedione, testosterone, dehydroepiandrostendione-sulfate (DHEA-S, estrone and estradiol by LC–MS/MS steroid profiling at baseline and one year later. Results: At baseline, obese PCOS girls demonstrated significantly higher androstenedione and testosterone concentrations compared to obese girls without PCOS, whereas the other steroid hormones including glucocorticoids, mineralocorticoids, estrogens and precursors of androgens did not differ significantly. Weight loss in obese PCOS girls was associated with a significant decrease of testosterone, androstenedione, DHEA-S, cortisol and corticosterone concentrations. Weight loss in obese non-PCOS girls was associated with a significant decrease of DHEA-S, cortisol and corticosterone concentrations, whereas no significant changes of testosterone and androstenedione concentrations could be observed. Without weight loss, no significant changes of steroid hormones were measured except an increase of estradiol in obese PCOS girls without weight loss. Conclusions: The key steroid hormones in obese adolescents with PCOS are androstenedione and testosterone, whereas glucocorticoids, mineralocorticoids, estrogens and precursors of androgens did not differ between obese girls with and without PCOS.

  18. Discovery of safety biomarkers for atorvastatin in rat urine using mass spectrometry based metabolomics combined with global and targeted approach

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    Kumar, Bhowmik Salil [Bioanalysis and Biotransformation Research Center, Korea Institute of Science and Technology, P.O. Box 131, Cheongryang, Seoul 130-650 (Korea, Republic of); University of Science and Technology, (305-333) 113 Gwahangno, Yuseong-gu, Daejeon (Korea, Republic of); Lee, Young-Joo; Yi, Hong Jae [College of Pharmacy, Kyung Hee University, Hoegi-dong, Dongdaemun-gu, Seoul 130-791 (Korea, Republic of); Chung, Bong Chul [Bioanalysis and Biotransformation Research Center, Korea Institute of Science and Technology, P.O. Box 131, Cheongryang, Seoul 130-650 (Korea, Republic of); Jung, Byung Hwa, E-mail: jbhluck@kist.re.kr [Bioanalysis and Biotransformation Research Center, Korea Institute of Science and Technology, P.O. Box 131, Cheongryang, Seoul 130-650 (Korea, Republic of); University of Science and Technology, (305-333) 113 Gwahangno, Yuseong-gu, Daejeon (Korea, Republic of)

    2010-02-19

    In order to develop a safety biomarker for atorvastatin, this drug was orally administrated to hyperlipidemic rats, and a metabolomic study was performed. Atorvastatin was given in doses of either 70 mg kg{sup -1} day{sup -1} or 250 mg kg{sup -1} day{sup -1} for a period of 7 days (n = 4 for each group). To evaluate any abnormal effects of the drug, physiological and plasma biochemical parameters were measured and histopathological tests were carried out. Safety biomarkers were derived by comparing these parameters and using both global and targeted metabolic profiling. Global metabolic profiling was performed using liquid chromatography/time of flight/mass spectrometry (LC/TOF/MS) with multivariate data analysis. Several safety biomarker candidates that included various steroids and amino acids were discovered as a result of global metabolic profiling, and they were also confirmed by targeted metabolic profiling using gas chromatography/mass spectrometry (GC/MS) and capillary electrophoresis/mass spectrometry (CE/MS). Serum biochemical and histopathological tests were used to detect abnormal drug reactions in the liver after repeating oral administration of atorvastatin. The metabolic differences between control and the drug-treated groups were compared using PLS-DA score plots. These results were compared with the physiological and plasma biochemical parameters and the results of a histopathological test. Estrone, cortisone, proline, cystine, 3-ureidopropionic acid and histidine were proposed as potential safety biomarkers related with the liver toxicity of atorvastatin. These results indicate that the combined application of global and targeted metabolic profiling could be a useful tool for the discovery of drug safety biomarkers.

  19. Lack of renal 11 beta-hydroxysteroid dehydrogenase type 2 at birth, a targeted temporal window for neonatal glucocorticoid action in human and mice.

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    Laetitia Martinerie

    Full Text Available BACKGROUND: Glucocorticoid hormones play a major role in fetal organ maturation. Yet, excessive glucocorticoid exposure in utero can result in a variety of detrimental effects, such as growth retardation and increased susceptibility to the development of hypertension. To protect the fetus, maternal glucocorticoids are metabolized into inactive compounds by placental 11beta-hydroxysteroid dehydrogenase type2 (11βHSD2. This enzyme is also expressed in the kidney, where it prevents illicit occupation of the mineralocorticoid receptor by glucocorticoids. We investigated the role of renal 11βHSD2 in the control of neonatal glucocorticoid metabolism in the human and mouse. METHODS: Cortisol (F and cortisone (E concentrations were measured in maternal plasma, umbilical cord blood and human newborn urine using HPLC. 11βHSD2 activity was indirectly assessed by comparing the F/E ratio between maternal and neonatal plasma (placental activity and between plasma and urine in newborns (renal activity. Direct measurement of renal 11βHSD2 activity was subsequently evaluated in mice at various developmental stages. Renal 11βHSD2 mRNA and protein expression were analyzed by quantitative RT-PCR and immunohistochemistry during the perinatal period in both species. RESULTS: We demonstrate that, at variance with placental 11βHSD2 activity, renal 11βHSD2 activity is weak in newborn human and mouse and correlates with low renal mRNA levels and absence of detectable 11βHSD2 protein. CONCLUSIONS: We provide evidence for a weak or absent expression of neonatal renal 11βHSD2 that is conserved among species. This temporal and tissue-specific 11βHSD2 expression could represent a physiological window for glucocorticoid action yet may constitute an important predictive factor for adverse outcomes of glucocorticoid excess through fetal programming.

  20. Activation of the baboon fetal hypothalamic-pituitary-adrenocortical axis at midgestation by estrogen-induced changes in placental corticosteroid metabolism

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    Pepe, G.J.; Waddell, B.J.; Albrecht, E.D. (Eastern Virginia Medical School, Norfolk (USA))

    1990-12-01

    We have hypothesized that the change in placental cortisol (F)-cortisone (E) metabolism induced by estrogen late in gestation is important to activation of the baboon fetal hypothalamic-pituitary-adrenocortical axis, culminating in the ontogenesis of de novo F secretion by the fetal adrenal. The present study tested this hypothesis in vivo by comparing the proportion of F in the fetus derived via maternal and fetal production on day 100 (n = 7; term = day 184) and day 165 (n = 4) in untreated baboons and on day 100 in baboons (n = 9) in which 50-mg pellets of androstenedione were implanted sc in the mother in increasing numbers (i.e. two on day 70, four on day 78, six on day 86, and eight on day 94) to increase placental estrogen production. Maternal, uterine, and umbilical venous samples were collected during constant maternal infusion (120 min) of (3H)F/(14C)E, endogenous and radiolabeled F/E content was determined, and corticosteroid dynamics were quantified. The MCR and peripheral interconversion of F and E as well as the production rate of F were unaltered in the mother. However, at midgestation, androstenedione increased (P less than 0.05) estrogen by 62% and altered transuterofeto placental F-E metabolism from preferential reduction of E to preferential oxidation of F, a pattern similar to that at term. In untreated baboons, on day 100 none of the F in the fetus was due to fetal production, whereas by day 165, 49 +/- 6% was of fetal origin. In animals treated with androstenedione at midgestation, 22 +/- 4% of fetal F was derived de novo within the fetus. Thus, production of F by the fetus was negligible on day 100, increased near term in association with an increase in transplacental oxidation of F to E, and was induced at midgestation in baboons in which placental F-E metabolism was altered by an increase in estrogen production.

  1. Association between ins4436A in 11β-hydroxysteroid dehydrogenase type 1 gene and essential hypertension in Polish population

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    Paulina Hejduk

    2015-11-01

    Full Text Available Background: Essential hypertension (EH is the most common cardiovascular disease worldwide, and it has a strong genetic component. Cortisol homeostasis is an important factor in controlling blood pressure, and the availability of this hormone is regulated by 11βhydroxysteroid dehydrogenase type 1 enzyme (11βHSD1, which converts cortisone into cortisol. Materials and Methods: We investigated the correlation between EH and the single nucleotide polymorphism (SNP ins4436A located on the hydroxysteroid (11-beta dehydrogenase 1 gene among the Polish population. The study included a total of 268 patients with confirmed EH and 151 unrelated controls. All studied polymorphisms were detected using the restriction fragment length polymorphism (RFLP method. Results: The carriage of ins4436A (rs45487298 polymorphism in intron 3 of the HSD11B1 gene was more frequent among patients with EH than among controls (p=0.013. The analysis of association of ins4436A with the risk of EH indicated an odds ratio (OR of 2.44 (95% confidential interval: 1.24-4.82. Moreover, essential hypertension occurred less frequently in males than in females. Results of multivariate analysis in the study group showed that ins4436A is a strong predictor of diabetes mellitus type 2 and ins4436A may lead to a decrease of the high-density lipoprotein (HDL cholesterol level.Discussion: The cause of essential hypertension has not been fully established, but genetic factors seem to play a very important role. In our study we found that ins4436A in the HSD11B1 gene was associated with essential hypertension in a Polish population. Nevertheless, the impact of ins4436A in the HSD11B1 gene on the occurrence of essential hypertension requires further investigations.

  2. Chemometric Evaluation of Urinary Steroid Hormone Levels as Potential Biomarkers of Neuroendocrine Tumors

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    Barbara Seroczyńska

    2013-10-01

    Full Text Available Neuroendocrine tumors (NETs are uncommon tumors which can secrete specific hormone products such as peptides, biogenic amines and hormones. So far, the diagnosis of NETs has been difficult because most NET markers are not specific for a given tumor and none of the NET markers can be used to fulfil the criteria of high specificity and high sensitivity for the screening procedure. However, by combining the measurements of different NET markers, they become highly sensitive and specific diagnostic tests. The aim of the work was to identify whether urinary steroid hormones can be identified as potential new biomarkers of NETs, which could be used as prognostic and clinical course monitoring factors. Thus, a rapid and sensitive reversed-phase high-performance liquid chromatographic method (RP-HPLC with UV detection has been developed for the determination of cortisol, cortisone, corticosterone, testosterone, epitestosterone and progesterone in human urine. The method has been validated for accuracy, precision, selectivity, linearity, recovery and stability. The limits of detection and quantification were 0.5 and 1 ng mL−1 for each steroid hormone, respectively. Linearity was confirmed within a range of 1–300 ng mL−1 with a correlation coefficient greater than 0.9995 for all analytes. The described method was successfully applied for the quantification of six endogenous steroid levels in human urine. Studies were performed on 20 healthy volunteers and 19 patients with NETs. Next, for better understanding of tumor biology in NETs and for checking whether steroid hormones can be used as potential biomarkers of NETs, a chemometric analysis of urinary steroid hormone levels in both data sets was performed.

  3. Protective Effector Cells of the Recombinant Asp f3 Anti-Aspergillosis Vaccine

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    Diana eDiaz-Arevalo

    2012-08-01

    Full Text Available An Aspergillus fumigatus vaccine based on recombinant Asp f3 protein has the potential to prevent aspergillosis in humans, a devastating fungal disease that is the prime obstacle to the success of hematopoietic cell transplantation. This vaccine protects cortisone acetate (CA-immunosuppressed mice from invasive pulmonary aspergillosis via CD4+ T cell mediators. Aside from these mediators, the nature of downstream fungicidal effectors is not well understood. Neutrophils and macrophages protect immunocompetent individuals from invasive fungal infections, and selective neutrophil depletion rendered mice susceptible to aspergillosis whereas macrophage depletion failed to increase fungal susceptibility. We investigated the effect of neutrophil depletion on rAsp f3 vaccine protection, and explored differences in pathophysiology and susceptibility between CA-immunosuppression and neutrophil depletion. In addition to being protective under CA-immunosuppression, the vaccine also had a protective effect in neutrophil-depleted mice. However, in non-immunized mice, a ten-fold higher conidial dose was required to induce similar susceptibility to infection with neutrophil-depletion than with CA- immunosuppression. The lungs of non-immunized neutrophil-depleted mice became invaded by a patchy dense mycelium with highly branched hyphae, and the peribronchial inflammatory infiltrate consisted mainly of CD3+ T cells and largely lacked macrophages. In contrast, lungs of non-immunized CA-immunosuppressed mice were more evenly scattered with short hyphal elements. With rAsp f3-vaccination, the lungs were largely clear of fungal burden under either immunosuppressive condition. We conclude that neutrophils, although substantial for innate antifungal protection of immunocompetent hosts, are not the relevant effectors for rAsp f3-vaccine derived protection of immunosuppressed hosts. It is therefore more likely that macrophages represent the crucial effectors of the r

  4. Protective Effect of Flowerbuds of Lonicera Japonica Extract on Diabetes Mellitus Type 2 and Associated Vascular Complications in STZ-HFD Treated Rats

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    Chiragkumar Amrutlal Prajapati

    2015-12-01

    Full Text Available Objective: To study the protective effect of Lonicera Japonica Alcoholic Extract (LJALE on Diabetes Mellitus  II (DM and associated vascular complications.Methods: Induction of Diabetes Mellitus II with 35 mg / kg STZ-HFD leads to excessive level of 11β-HSD1 enzyme. It has been found that flower buds of Lonicera Japonica (LJ has also been traditionally indicated for treatment of diabetes. Chlorogenic Acid (CA is a major bioactive component in the flower buds of LJ has received more attention because of its 11β-HSD1 inhibitory action.11β-HSD1 regulates glucocorticoid action at the pre-receptor stage by converting cortisone to cortisol. Elevated glucocorticoids are a key risk factor for metabolic diseases. LJALE was prepared with help of Microwave Assisted Extraction (MAE method.  STZ-HFD-induced diabetic rats were treated with LJALE (200 mg/kg, 500 mg/kg and Metformin (50 mg/kg. It was given for 4 weeks.Result: LJALE treated Diabetic rats showed significant decreased in blood glucose levels, plasma insulin, serum cortisol as well significant increased hepatic glycogen, 11β-HSD1 index compare to diabetic control rats. LJALE (500 mg/kg treatment showed the return of islets close to good vascular pattern. LJALE treatment restored endothelium dysfunction.Conclusions: From all results it is reasonable to conclude that LJALE (500 mg/kg may be used in treatment of diabetes and diabetes associated vascular dysfunction.Keywords:  Diabetes Mellitus, 11β-HSD1, CA, LJALE

  5. Stability indicating methods for the determination of some anti-fungal agents using densitometric and RP-HPLC methods.

    Science.gov (United States)

    Mousa, Bahia Abbas; El-Kousy, Naglaa Mahmoud; El-Bagary, Ramzia Ismail; Mohamed, Nashwah Gadalla

    2008-02-01

    Two chromatographic methods were developed for the determination of some anti-fungal drugs in the presence of either their degradation products or cortisone derivatives. The densitometric method determined mixtures of each of ketoconazole (KT), clotrimazole (CL), miconazole nitrate (MN) and econazole nitrate (EN) with the degradation products of each one. Mixtures of MN with hydrocortisone (HC) and of EN with triamcinolone acetonide (TA) were also successfully separated and determined by this technique. For KT and CL, a mixture of methanol:water:triethylamine (70:28:2 v/v) was used as a developing system and the spots were scanned at 243 nm and 220 nm for KT and CL, respectively. For MN and EN, a mixture of hexane:isopropyl alcohol:triethylamine (80:17:3 v/v) was used as a developing system and the spots were scanned at 225 nm for both drugs. The HPLC method determined mixtures of CL or EN with their degradation products which were separated and quantified on a Zorbax C8 column. Elution was carried out using methanol:phosphate buffer pH 2.5 (65:35 v/v) as a mobile phase at a flow rate of 1.5 ml/min and UV detection at 220 nm for CL. For EN, a mixture of methanol:water containing 0.06 ml triethylamine pH 10 (75:25 v/v) was used as a mobile phase at a flow rate of 1.5 ml/min and UV detection at 225 nm. The methods were also used to separate mixtures of CL with betamethasone dipropionate (BD) and EN with TA in a laboratory prepared mixture and in pharmaceutical preparations. The methods were sensitive, precise and applicable for determination of the drugs in pharmaceutical dosage forms.

  6. Ultraviolet- and infrared-induced 11 beta-hydroxysteroid dehydrogenase type 1 activating skin photoaging is inhibited by red ginseng extract containing high concentration of ginsenoside Rg3(S).

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    Nam, Jin-Ju; Min, Ji-Eun; Son, Min-Ho; Oh, Jin-Hwan; Kang, Seunghyun

    2017-08-09

    Sun irradiation is one of major extrinsic stressors responsible for premature skin aging through activation and expression of 11 beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1), which converts inactive cortisone to active cortisol. The aim of this study was to evaluate the inhibitory effects of red ginseng extract containing high concentrations of ginsenoside Rg3 (S) (GERg3) on 11β-HSD1-induced skin photoaging. To evaluate the inhibitory effects of GERg3 on ultraviolet- (UV) or infrared (IR)-induced skin photoaging, human dermal fibroblasts or a normal human 3D skin model was exposed to UV or an IR. RT-PCR, ELISA, Western blot, and H&E staining were used for evaluations. GERg3 was isolated from crude red ginseng. GERg3 inhibited the increased expressions of 11β-HSD1, interleukin (IL)-6, and matrix metalloproteinase-1 (MMP-1) in UVB- or IR-exposed Hs68 cells. Additionally, the increased cortisol, IL-6, and MMP-1 expressions were effectively reduced by GERg3 in UVA-exposed 3D skin models. The photoinduced decrease in type 1 procollagen also recovered as a result of GERg3 treatment in Hs68 cells and the 3D skin model. In addition, the UVA-exposed dermal thickness was decreased in comparison with the UVA-protected 3D skin model, recovered with GERg3 treatment. GERg3 had antiphotoaging effects in UV- or IR-exposed human dermal fibroblasts and normal human 3D skin model. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Automated coupling of capillary-HPLC to matrix-assisted laser desorption/ionization mass spectrometry for the analysis of small molecules utilizing a reactive matrix.

    Science.gov (United States)

    Brombacher, Stephan; Owen, Stacey J; Volmer, Dietrich A

    2003-07-01

    This study describes the application of a novel, reactive matrix for the mass spectral analysis of steroids by capillary-high performance liquid chromatography (capillary-HPLC) coupled to matrix-assisted laser desorption/ionization (MALDI). The mass spectral analysis of steroids was accomplished after fully automated peak deposition of chromatographic peaks onto MALDI targets. The seven corticosteroids used as test compounds were: triamcinolone, prednisone, cortisone, fludrocortisone, dexamethasone, deoxycorticosterone, and budesonide. They were separated using a PepMap C(18) (3 microm particle size, 100 A pore width) column at five different concentration levels of 25, 15, 7.5, 2.5 and 1 ng/microL, and the peaks were detected at a wavelength of 237 nm. The column effluent was mixed with 2,4-dinitrophenylhydrazine (DNPH) directly following the UV detector. The chromatographic peaks were then deposited onto the MALDI target with a robotic micro-fraction collector triggered by the UV detector signals. A special hydrophobic surface coating allowed the deposition of up to 4 microL (up to 90 % of the chromatographic peak volume) onto one sample spot. The compounds were then identified by MALDI mass spectrometry. Depending on the nature of the analyte, radical cations ([M](+.)) and sodium adduct ions ([M+Na](+)) of the steroids as well as protonated steroid-dinitrophenylhydrazone derivatives ([M(D)+H](+)) were detected in positive ion mode. The detection limits were between 0.5 and 15 ng injected with capillary-HPLC-MALDI-TOF-MS and between 0.3 and 3 ng on target with MALDI-TOF when deposited manually.

  8. [The high pressure liquid chromatography of corticoids. II. Analysis of synthetic corticoids in blood and urine (author's transl)].

    Science.gov (United States)

    Saito, Z; Amatsu, E; Ono, T; Hihumi, S; Mimou, T; Hashiba, T; Sakato, S; Miyamoto, M; Takeda, R

    1979-10-20

    The high pressure liquid chromatographic (HPLC) technique was developed to separate and quantitate the synthetic corticosteroids (s-CS) which are widely used clinically. 1) 12 kinds of s-CS in alcoholic solvent and 2) some of their metabolites in the plasma and urine of healthy subjects with oral administration of s-CS were investigated for the preliminary work. The results are summarized as follows: 1) Cortisol sodium phosphate, Dexamethasone 21, disodium phosphate, Paramethasone acetate, Cortisol acetate, Cortisone acetate, Methylprednisolone acetate, Prednisone, Dexamethasone, 9 alpha-fluorocortisol, Betamethasone, Triamcinolone, and Prednisolone in ethanol were clearly separated by HPLC from Cortisol (F). In the suitable condition of the HPLC (LC-2 type) with a Zorbax SIL column, organic solvent (cyclohexane:dichloromethane:ethanol = 9:4:1)-carrier mobile phases and UV detector, the retention time of each s-CS was obviously different from that of F. The calibration curve was obtained in a linear line with regards to each s-CS. The mean recovery was 97.6% and the coefficient of variation were 1.6 (intraassay) and 7.2 (interassay)%. The sensitivity of the steroid determination was 200pg order. 2) The serial changes in plasma concentrations of s-CS; CS-metabolites and endogenous F were shown in 3 healthy males and 2 females following oral administration of the s-CS. The separated metabolites in number and quality depended on the kind of s-CS. Prednisone and other kinds of the acidified products were separated from prednisolone in the plasma and urinary samples of the healthy subjects as well as Addisonian patients. In conclusion, the HPLC method is useful for the separation and quantitation of the UV-absorbing CS of human plasma and urine. The obtained chromatograms may be an indication of the metabolic state of the subject with treatment of s-CS.

  9. 11β-Hydroxysteroid dehydrogenase 1 contributes to the pro-inflammatory response of keratinocytes.

    Science.gov (United States)

    Itoi, Saori; Terao, Mika; Murota, Hiroyuki; Katayama, Ichiro

    2013-10-18

    The endogenous glucocorticoid, cortisol, is released from the adrenal gland in response to various stress stimuli. Extra-adrenal cortisol production has recently been reported to occur in various tissues. Skin is known to synthesize cortisol through a de novo pathway and through an activating enzyme. The enzyme that catalyzes the intracellular conversion of hormonally-inactive cortisone into active cortisol is 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1). We recently reported that 11β-HSD1 is expressed in normal human epidermal keratinocytes (NHEKs) and negatively regulates proliferation of NHEKs. In this study, we investigated the role of 11β-HSD1 in skin inflammation. Expression of 11β-HSD1 was induced by UV-B irradiation and in response to the pro-inflammatory cytokines, IL-1β and TNFα. Increased cortisol concentrations in culture media also increased in response to these stimuli. To investigate the function of increased 11β-HSD1 in response to pro-inflammatory cytokines, we knocked down 11β-HSD1 by transfecting siRNA. Production of IL-6 and IL-8 in response to IL-1β or TNFα stimulation was attenuated in NHEKs transfected with si11β-HSD1 compared with control cells. In addition, IL-1β-induced IL-6 production was enhanced in cultures containing 1 × 10(-13) M cortisol, whereas 1 × 10(-5) M cortisol attenuated production of IL-6. Thus, cortisol showed immunostimulatory and immunosuppressive activities depending on its concentration. Our results indicate that 11β-HSD1 expression is increased by various stimuli. Thus, regulation of cytosolic cortisol concentrations by 11β-HSD1 appears to modulate expression of inflammatory cytokines in NHEKs. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. Computer-aided strategies for archive retrieval and sensitivity enhancement in the identification of drugs by photodiode array detection in high-performance liquid chromatography.

    Science.gov (United States)

    Fell, A F; Clark, B J; Scott, H P

    1984-12-21

    An archive retrieval algorithm for high-performance liquid chromatography with UV detection (HPLC-UV) has been developed for the first time for the rapid identification of spectra acquired by rapid-scanning photodiode array detection in HPLC. The algorithm is based on a database of spectra (normalised with respect to area), inverse files of key spectral features, a selective search window, with parabolic weighting factors and least-squares comparison of test and retrieved spectra. The performance of the library search system is demonstrated with respect to a small library of solutes, including: cortisone acetate, ethynyl estradiol, ethisterone, progesterone; caffeine, theobromine, theophylline and 8-chlorotheophylline; morphine and diamorphine; and cycloserine. Since photodiode array detection operates in the domains of both wavelength and time, to generate a matrix of (A, lambda, t) data, the optimum conditions for sensitivity enhancement by ensemble averaging in these domains have been examined. At a given observation wavelength, increase in the detector bandwidth (or "diode bunching") yields a value of delta lambda which gives optimum sensitivity; this value is systematically related to the spectral bandwidth of the analyte. Sensitivity can also be optimised by varying the integration period in the time domain. Sensitivity can be further increased by combination of these instrumental optima, for which there is evidence of dependence on the particular instrument design. Response was found to be linear for detector bandwidths up to twice the optimum value. The comparative sensitivity of some commercially-available photodiode array detectors has been assessed relative to that of conventional detectors under strictly controlled conditions.

  11. [A reverse phase high performance liquid chromatography-UV spectrometry method for the analysis of several intrinsic adrenal delta 4-steroid concentrations].

    Science.gov (United States)

    Saisho, S; Shimozawa, K; Yata, J

    1986-12-20

    Taking an advantage of the property of delta 4-steroid that have a maximum absorbance around 250 nm wave-length of ultraviolet, we devised an assay method for the determination of serum delta 4-steroids concentration using a reverse phase high performance liquid chromatography (HPLC)-UV spectrometry. The assay procedure was as follows: A mixed solvent containing methanol, acetonitrile and water in 55/3/42 by volume was used as a mobile phase, and which was pumped at a constant flow rate of 1.5 ml/min. The main column and precolumn used were ERC-ODS-1161 (phi 6 mm X 10 cm) and ERC-ODS-1652 (phi 6mm X 3 cm), respectively. Two liquid-liquid extraction methods were used. One was a conventional method using dichloromethane for an extraction solvent, and the other was a simplified method using Extrelut column and ethyl acetate. Before a practical assay we examined the retention time of each steroid determined and its ratio of peak height to that of the internal standard (dexamethasone). We found good correlations between the concentrations of cortisol (F), 17 alpha-hydroxyprogesterone (17-OHP) and 21-deoxycortisol (21-DOF) estimated by this HPLC method and those by highly specific radioimmunoassay method. The concentrations of cortisone (E) and F of eight umbilical venous blood specimens were 159.7 +/- 26.3 (Mean +/- SD) ng/ml and 93.3 +/- 58.9 ng/ml, respectively, and 17-OHP was detected 7 of them and its concentration was 17.4 +/- 12.4 ng/ml. On the other hand, 17-OHP and 21-DOF peaks could not be detected in 1 month old normal infants.(ABSTRACT TRUNCATED AT 250 WORDS)

  12. Chemometric evaluation of urinary steroid hormone levels as potential biomarkers of neuroendocrine tumors.

    Science.gov (United States)

    Plenis, Alina; Miękus, Natalia; Olędzka, Ilona; Bączek, Tomasz; Lewczuk, Anna; Woźniak, Zofia; Koszałka, Patrycja; Seroczyńska, Barbara; Skokowski, Jarosław

    2013-10-16

    Neuroendocrine tumors (NETs) are uncommon tumors which can secrete specific hormone products such as peptides, biogenic amines and hormones. So far, the diagnosis of NETs has been difficult because most NET markers are not specific for a given tumor and none of the NET markers can be used to fulfil the criteria of high specificity and high sensitivity for the screening procedure. However, by combining the measurements of different NET markers, they become highly sensitive and specific diagnostic tests. The aim of the work was to identify whether urinary steroid hormones can be identified as potential new biomarkers of NETs, which could be used as prognostic and clinical course monitoring factors. Thus, a rapid and sensitive reversed-phase high-performance liquid chromatographic method (RP-HPLC) with UV detection has been developed for the determination of cortisol, cortisone, corticosterone, testosterone, epitestosterone and progesterone in human urine. The method has been validated for accuracy, precision, selectivity, linearity, recovery and stability. The limits of detection and quantification were 0.5 and 1 ng mL-1 for each steroid hormone, respectively. Linearity was confirmed within a range of 1-300 ng mL-1 with a correlation coefficient greater than 0.9995 for all analytes. The described method was successfully applied for the quantification of six endogenous steroid levels in human urine. Studies were performed on 20 healthy volunteers and 19 patients with NETs. Next, for better understanding of tumor biology in NETs and for checking whether steroid hormones can be used as potential biomarkers of NETs, a chemometric analysis of urinary steroid hormone levels in both data sets was performed.

  13. The role of ACTH and adrenal glucocorticoids in the salt appetite of wild rabbits (Oryctolagus cuniculus (L)).

    Science.gov (United States)

    Blaine, E H; Covelli, M D; Denton, D A; Nelson, J F; Shulkes, A A

    1975-10-01

    The selective appetites of wild rabbits for 500 mEq/1 solutions of NaC1, KC1, MgC1(2), and CaC1(2) were studied in intact and adrenalectomized rabbits during daily treatment with either 4 IU long acting ACTH, 1.0 or 2.5 mg cortisol acetate, or 2.5 mg corticosterone. The animals were individually caged and external sodium balances performed. In intact rabbits, cortisol or corticosterone produced a significant stimulation of NaC1 appetite. The response to concurrent dosage of cortisol and corticosterone was less than half of that obtained with ACTH which produced a comparable alteration of blood glucocorticoid levels but a 10-fold increase in NaC1 intake. CaC1(2) intake was increased in intact rabbits by cortisol treatment but not by corticosterone or ACTH. Adrenalectomized rabbits maintained on daily steroid replacement therapy of 0.1 mg deoxycorticosterone acetate and 0.75 mg cortisone acetate showed a normal pattern of electolyte, food, and water intake. Under these conditions ACTH produced a 4-fold increase in NaC1 intake. Further addition of cortisol and corticosterone to steroid replacement therapy produced an increase in NaC1 intake comparable to their effect on normal rabbits. Thereupon supplementation with ACTH resulted in an increase to a level at least as great as that found in ACTH treated, normal rabbits. The effects of ACTH and glucocorticoids on NaC1 appetite were synergistic. Sodium balance showed that increases in NaC1 intake were not the result of the treatment initially producing a body sodium deficit, which was then corrected by increased intake. The results provide further evidence for the hypothesis that NaC1 appetite may be hormonally regulated, and demonstrate that ACTH is capable of stimulating NaC1 intake by a previously unsuspected non-adrenal pathway.

  14. Application progress of 11-βHSD in the human placental barrier effect of glucocorticoid%11-β羟基类固醇脱氢酶在人类胎盘对糖皮质激素的屏障作用的研究进展

    Institute of Scientific and Technical Information of China (English)

    魏来

    2013-01-01

    11-β羟基类固醇脱氢酶(11β-hydroxysteroid dehydrogenase,11β-HSD)是胎盘分泌的糖皮质激素(glucoeorticoids,GC)代谢酶,对胎盘与胎膜的作用有重要影响,同时阻挡着母体GC过多的进入胎儿,避免造成胎儿体质下降、日后并发糖尿病的危害.11β-HSD有两种亚型,11β-HSD1是一种亲和力较低的氧化还原酶,并且主要表现还原酶活性,主要是活化无活性的17-羟-11-脱氢皮质酮(cortisone,E)为有活性的皮质酮(cortisol,F),因此具有GC再生和增效的作用;11β-HSD2是一种亲和力较高的依赖性脱氢酶,表现单一氧化酶作用,它主要是催化皮质醇将其由有活性状态转化为无活性状态,从而阻挡母体浓度高于胎儿水平5~10倍的GC进入胎盘中,形成保障胎儿正常生长发育的GC屏障.

  15. Unmet needs in the treatment of autoimmunity: from aspirin to stem cells.

    Science.gov (United States)

    Chang, Christopher

    2014-01-01

    As rheumatologic diseases became understood to be autoimmune in nature, the drugs used to treat this group of conditions has evolved from herbal or plant derived anti-inflammatory agents, such as salicylates, quinine and colchicine to the many recently approved biological response modifiers. These new drugs, especially the anti-tumor necrosis factor agents, have shown remarkable efficacy in autoimmune diseases, and there are new agents under investigation that will provide additional treatment options. In between, the world was introduced to cortisone and all of its derivatives, as chemical synthesis led to better, more efficacious drugs with lesser side effects. Disease modifying anti-rheumatic agents have actually been around since the first half of the 20th century, but only began to be used in the treatment of autoimmune diseases in the 1970s and 1980s. One advantage is that they have been invaluable in their ability to offer "steroid sparing" to decrease the adverse effects of steroids. Research over the past decade has resulted in a new class of drugs that influence cytokine regulatory pathways such as the Janus associated kinase inhibitors. The promise of personalized medicine now permeates current research into new pharmacological agents for the treatment of autoimmune disease. The new appreciation for the gene-environment interaction in the pathogenesis of most diseases especially those as heterogeneous as autoimmune diseases, has led to our focus on targeted therapies. Add to that the new knowledge of epigenetics and how changes in DNA and histone structure affect expression of genes that can play a role in immune signaling, and we now have a new exciting frontier for cutting edge drug development. The history of treatment of autoimmune diseases is really only a little over a century, but so much has changed, leading to increasing lifespans and improved quality of life of those who suffer from these ailments. Copyright © 2014. Published by Elsevier B.V.

  16. Glucocorticoids reduce phobic fear in humans.

    Science.gov (United States)

    Soravia, Leila M; Heinrichs, Markus; Aerni, Amanda; Maroni, Caroline; Schelling, Gustav; Ehlert, Ulrike; Roozendaal, Benno; de Quervain, Dominique J-F

    2006-04-04

    Phobias are characterized by excessive fear, cued by the presence or anticipation of a fearful situation. Whereas it is well established that glucocorticoids are released in fearful situations, it is not known whether these hormones, in turn, modulate perceived fear. As extensive evidence indicates that elevated glucocorticoid levels impair the retrieval of emotionally arousing information, they might also inhibit retrieval of fear memory associated with phobia and, thereby, reduce phobic fear. Here, we investigated whether acutely administrated glucocorticoids reduced phobic fear in two double-blind, placebo-controlled studies in 40 subjects with social phobia and 20 subjects with spider phobia. In the social phobia study, cortisone (25 mg) administered orally 1 h before a socio-evaluative stressor significantly reduced self-reported fear during the anticipation, exposure, and recovery phase of the stressor. Moreover, the stress-induced release of cortisol in placebo-treated subjects correlated negatively with fear ratings, suggesting that endogenously released cortisol in the context of a phobic situation buffers fear symptoms. In the spider phobia study, repeated oral administration of cortisol (10 mg), but not placebo, 1 h before exposure to a spider photograph induced a progressive reduction of stimulus-induced fear. This effect was maintained when subjects were exposed to the stimulus again 2 days after the last cortisol administration, suggesting that cortisol may also have facilitated the extinction of phobic fear. Cortisol treatment did not reduce general, phobia-unrelated anxiety. In conclusion, the present findings in two distinct types of phobias indicate that glucocorticoid administration reduces phobic fear.

  17. Epicondilite lateral do cotovelo Lateral epicondylitis of the elbow

    Directory of Open Access Journals (Sweden)

    Marcio Cohen

    2012-01-01

    Full Text Available A epicondilite lateral, também conhecida como cotovelo do tenista, é uma condição comum que acomete de 1 a 3% da população. O termo epicondilite sugere inflamação, embora a análise histológica tecidual não demonstre um processo inflamatório. A estrutura acometida com mais frequência é a origem do tendão extensor radial curto do carpo e o mecanismo de lesão está associado à sua sobrecarga. O tratamento incruento é o de escolha e inclui: repouso, fisioterapia, infiltração com cortisona ou plasma rico em plaquetas e a utilização de imobilização específica. O tratamento cirúrgico é recomendado quando persistem impotência funcional e dor. Tanto a técnica cirúrgica aberta quanto a artroscópica com ressecção da área tendinosa degenerada apresenta bons resultados na literatura.Lateral epicondylitis, also known as tennis elbow, is a common condition that is estimated to affect 1% to 3% of the population. The word epicondylitis suggests inflammation, although histological analysis on the tissue fails to show any inflammatory process. The structure most commonly affected is the origin of the tendon of the extensor carpi radialis brevis and the mechanism of injury is associated with overloading. Nonsurgical treatment is the preferred method, and this includes rest, physiotherapy, cortisone infiltration, platelet-rich plasma injections and use of specific immobilization. Surgical treatment is recommended when functional disability and pain persist. Both the open and the arthroscopic surgical technique with resection of the degenerated tendon tissue present good results in the literature.

  18. Acute effects of physical exercise and phosphodiesterase's type 5 inhibition on serum 11β-hydroxysteroid dehydrogenases related glucocorticoids metabolites: a pilot study.

    Science.gov (United States)

    Di Luigi, Luigi; Botrè, Francesco; Sabatini, Stefania; Sansone, Massimiliano; Mazzarino, Monica; Guidetti, Laura; Baldari, Carlo; Lenzi, Andrea; Caporossi, Daniela; Romanelli, Francesco; Sgrò, Paolo

    2014-12-01

    Endogenous glucocorticoids (GC) rapidly increase after acute exercise, and the phosphodiesterase's type 5 inhibitor (PDE5i) tadalafil influences this physiological adaptation. No data exist on acute effects of both acute exercise and PDE5i administration on 11β-hydroxysteroid dehydrogenases (11β-HSDs)-related GC metabolites. We aimed to investigate the rapid effects of exercise on serum GC metabolites, with and without tadalafil administration. A double blind crossover study was performed in eleven healthy male volunteers. After the volunteers randomly received a short-term administration of placebo or tadalafil (20 mg/die for 2 days), a maximal exercise test to exhaustion on cycle ergometer was performed. Then, after a 2-week washout period, the volunteers were crossed over. Blood samples were collected before starting exercise and at 5 and 30 min of recovery (+5-Rec, +30-Rec). Serum ACTH, corticosterone (Cn), cortisol (F), cortisone (E), tetrahydrocortisol (THF), tetrahydrocortisone (THE), cortols, cortolones and respective ratios were evaluated. Pre-Ex THF was higher after tadalafil. Exercise increased ACTH, Cn, F, E, THE, cortols and cortolones after both placebo and tadalafil, and THF after placebo. The F/E ratio increased at +5-Rec and decreased at +30-Rec after placebo. Compared to placebo, after tadalafil lower ACTH, F and Cn, higher THF/F and THE/E, and not E (at +5-Rec) and F/E modifications were observed. Acute exercise rapidly influences serum GC metabolites concentrations. Tadalafil influences both GC adaptation and 11β-HSDs activity during acute exercise. Additional researches on the effects of both exercise and PDE5i on tissue-specific 11β-HSDs activity at rest and during physiological adaptation are warranted.

  19. Glucocorticoid Clearance and Metabolite Profiling in an In Vitro Human Airway Epithelium Lung Model.

    Science.gov (United States)

    Rivera-Burgos, Dinelia; Sarkar, Ujjal; Lever, Amanda R; Avram, Michael J; Coppeta, Jonathan R; Wishnok, John S; Borenstein, Jeffrey T; Tannenbaum, Steven R

    2016-02-01

    The emergence of microphysiologic epithelial lung models using human cells in a physiologically relevant microenvironment has the potential to be a powerful tool for preclinical drug development and to improve predictive power regarding in vivo drug clearance. In this study, an in vitro model of the airway comprising human primary lung epithelial cells cultured in a microfluidic platform was used to establish a physiologic state and to observe metabolic changes as a function of glucocorticoid exposure. Evaluation of mucus production rate and barrier function, along with lung-specific markers, demonstrated that the lungs maintained a differentiated phenotype. Initial concentrations of 100 nM hydrocortisone (HC) and 30 nM cortisone (C) were used to evaluate drug clearance and metabolite production. Measurements made using ultra-high-performance liquid chromatography and high-mass-accuracy mass spectrometry indicated that HC metabolism resulted in the production of C and dihydrocortisone (diHC). When the airway model was exposed to C, diHC was identified; however, no conversion to HC was observed. Multicompartmental modeling was used to characterize the lung bioreactor data, and pharmacokinetic parameters, including elimination clearance and elimination half-life, were estimated. Polymerse chain reaction data confirmed overexpression of 11-β hydroxysteroid dehydrogenase 2 (11βHSD2) over 11βHSD1, which is biologically relevant to human lung. Faster metabolism was observed relative to a static model on elevated rates of C and diHC formation. Overall, our results demonstrate that this lung airway model has been successfully developed and could interact with other human tissues in vitro to better predict in vivo drug behavior.

  20. Glucocorticoid activity and metabolism with NaCl-induced low-grade metabolic acidosis and oral alkalization: results of two randomized controlled trials.

    Science.gov (United States)

    Buehlmeier, Judith; Remer, Thomas; Frings-Meuthen, Petra; Maser-Gluth, Christiane; Heer, Martina

    2016-04-01

    Low-grade metabolic acidosis (LGMA), as induced by high dietary acid load or sodium chloride (NaCl) intake, has been shown to increase bone and protein catabolism. Underlying mechanisms are not fully understood, but from clinical metabolic acidosis interactions of acid-base balance with glucocorticoid (GC) metabolism are known. We aimed to investigate GC activity/metabolism under alkaline supplementation and NaCl-induced LGMA. Eight young, healthy, normal-weight men participated in two crossover designed interventional studies. In Study A, two 10-day high NaCl diet (32 g/d) periods were conducted, one supplemented with 90 mmol KHCO3/day. In Study B, participants received a high and a low NaCl diet (31 vs. 3 g/day), each for 14 days. During low NaCl, the diet was moderately acidified by replacement of a bicarbonate-rich mineral water (consumed during high NaCl) with a non-alkalizing drinking water. In repeatedly collected 24-h urine samples, potentially bioactive-free GCs (urinary-free cortisol + free cortisone) were analyzed, as well as tetrahydrocortisol (THF), 5α-THF, and tetrahydrocortisone (THE). With supplementation of 90 mmol KHCO3, the marker of total adrenal GC secretion (THF + 5α-THF + THE) dropped (p = 0.047) and potentially bioactive-free GCs were reduced (p = 0.003). In Study B, however, GC secretion and potentially bioactive-free GCs did not exhibit the expected fall with NaCl-reduction as net acid excretion was raised by 30 mEq/d. Diet-induced acidification/alkalization affects GC activity and metabolism, which in case of long-term ingestion of habitually acidifying western diets may constitute an independent risk factor for bone degradation and cardiometabolic diseases.