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

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

Controlled release of cortisone drugs from block copolymers synthetized by ATRP

International Nuclear Information System (INIS)

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

2016-01-01

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, "1"3C-NMR, CosY), SEC, TGA and DSC. Monitoring of drug release from films loaded with BDP was carried out by HPLC analysis. Evaluation of different

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

International Nuclear Information System (INIS)

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

1984-01-01

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 [ 3 H]F and 9-15 microCi [ 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)

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.

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Stéphanie M Boudon

Full Text Available 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.

Lymphocyte depletion in thymic nurse cells: a tool to identify in situ lympho-epithelial complexes having thymic nurse cell characteristics

NARCIS (Netherlands)

Leene, W.; de Waal Malefijt, R.; Roholl, P. J.; Hoeben, K. A.

1988-01-01

In situ pre-existing complexes of epithelial cells and thymocytes having thymic nurse cell characteristics were visualized in the murine thymus cortex using dexamethasone as a potent killer of cortisone-sensitive thymocytes. The degradation and subsequent depletion of cortisone-sensitive thymocytes

Is There an Association Between Cortisol and Hypertension in Overweight or Obese Children?

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Wirix, Aleid Jg; Finken, Martijn Jj; von Rosenstiel-Jadoul, Ines A; Heijboer, Annemieke C; Nauta, Jeroen; Groothoff, Jaap W; Chinapaw, Mai Jm; Kist-van Holthe, Joana E

2017-12-15

The precise mechanisms behind the development of hypertension in overweight or obese children are not yet completely understood. Alterations in hypothalamic-pituitary-adrenal axis activity may play a role. We aimed to investigate the association between cortisol parameters and hypertension in overweight or obese children. Random urine (n=180) and early-morning saliva samples (n=126) for assessment of cortisol and cortisone were collected from 1) hypertensive overweight children (n=50), 2) normotensive overweight children (n=145), and 3) normotensive non-overweight children (n=75). The age of participants was 10.4±3.3 years and 53% were boys. The urinary cortisol-to-cortisone ratio [β 1.11, 95% confidence interval (CI) 1.05-1.19] as well as urinary cortisol/creatinine (β 1.38, 95% CI 1.09-1.54), and cortisone/creatinine ratios (β 1.26, 95% CI 1.17-1.36) were significantly higher in overweight or obese than in non-overweight children. After adjusting for body mass index-standard deviation score and urinary cortisone/creatinine ratio, but not cortisol/creatinine ratio, was significantly associated with presence of hypertension (β 1.12, 95% CI 1.02-1.23). Salivary cortisol and cortisone levels were significantly lower in overweight or obese than in non-overweight children (β -4.67, 95% CI -8.19- -1.15, and β 0.89, 95% CI 0.80-0.97 respectively). There were no significant differences in cortisol parameters between hypertensive and normotensive overweight or obese children. This study provided further evidence for an increased cortisol production rate with decreased renal 11β-hydroxysteroid dehydrogenase 2 activity and flattening of early-morning peak cortisol and cortisone in overweight or obese children. However, there were no significant differences in cortisol parameters between hypertensive and normotensive overweight and obese children.

Enterocolite necrosante: resposta imflamatória x corticoterapia pré-natal

OpenAIRE

Precioso, Alexander Roberto; Proença, Renata Suman Mascaretti

2002-01-01

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 gastroin...

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

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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.

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

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

Science.gov (United States)

Marciniec, B.; 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 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.

Cortisol metabolism in healthy young adults: sexual dimorphism in activities of A-ring reductases, but not 11beta-hydroxysteroid dehydrogenases.

Science.gov (United States)

Finken, M J; Andrews, R C; Andrew, R; Walker, B R

1999-09-01

Cortisol is metabolized irreversibly by A-ring reductases (5alpha- and 5beta-reductases) and reversibly (to cortisone) by 11beta-hydroxysteroid dehydrogenases (11betaHSDs). In rats, estradiol down-regulates 11betaHSD1 expression. In humans, ratios of urinary cortisol/cortisone metabolites differ in men and women. In this study, urinary cortisol metabolites and hepatic 11betaHSD1 activity were measured in healthy young men and women at different phases of the menstrual cycle. Ten men and 10 women with regular menstrual cycles collected a 24-h urine sample, took 250 microg oral dexamethasone at 2300 h, took 25 mg oral cortisone at 0900 h (after fasting), and had blood sampled for plasma cortisol estimation over the subsequent 150 min. Women repeated the tests in random order in menstrual, follicular, and luteal phases. Women excreted disproportionately less A-ring-reduced metabolites of cortisol [median 5alpha-tetrahydrocortisol, 1811 (interquartile range, 1391-2300) microg/day in menstrual phase vs. 2723 (interquartile range, 2454-3154) in men (P = 0.01); 5beta-tetrahydrocortisol, 1600 (interquartile range, 1419-1968) vs. 2197 (interquartile range, 1748-2995; P = 0.03)] but similar amounts of cortisol, cortisone, and tetrahydrocortisone. Analogous differences were observed in urinary excretion of androgen metabolites. Conversion of cortisone to cortisol on hepatic first pass metabolism was not different (peak plasma cortisol, 733 +/- 60 nmol/L in women vs. 684 +/- 53 nmol/L in men; mean +/- SEM; P = 0.55). There were no differences in cortisol or androgen metabolism between phases of the menstrual cycle. We conclude that sexual dimorphism in cortisol metabolite excretion is attributable to less A-ring reduction of cortisol in women, rather than less reactivation of cortisone to cortisol by 11betaHSD1. This difference is not influenced acutely by gonadal steroids. 11BetaHSD1 has been suggested to modulate insulin sensitivity and body fat distribution, but caution

Efficacy of Liposomal Amphotericin B and Posaconazole in Intratracheal Models of Murine Mucormycosis

Science.gov (United States)

Luo, Guanpingsheng; Gebremariam, Teclegiorgis; Lee, Hongkyu; French, Samuel W.; Wiederhold, Nathan P.; Patterson, Thomas F.; Filler, Scott G.

2013-01-01

Mucormycosis is a life-threatening fungal infection almost uniformly affecting diabetics in ketoacidosis or other forms of acidosis and/or immunocompromised patients. Inhalation of Mucorales spores provides the most common natural route of entry into the host. In this study, we developed an intratracheal instillation model of pulmonary mucormycosis that hematogenously disseminates into other organs using diabetic ketoacidotic (DKA) or cyclophosphamide-cortisone acetate-treated mice. Various degrees of lethality were achieved for the DKA or cyclophosphamide-cortisone acetate-treated mice when infected with different clinical isolates of Mucorales. In both DKA and cyclophosphamide-cortisone acetate models, liposomal amphotericin B (LAmB) or posaconazole (POS) treatments were effective in improving survival, reducing lungs and brain fungal burdens, and histologically resolving the infection compared with placebo. These models can be used to study mechanisms of infection, develop immunotherapeutic strategies, and evaluate drug efficacies against life-threatening Mucorales infections. PMID:23650163

Distribution of Exogenous and Endogenous CYP3A Markers and Related Factors in Healthy Males and Females.

Science.gov (United States)

Lee, Jieon; Kim, Andrew HyoungJin; Yi, SoJeong; Lee, SeungHwan; Yoon, Seo Hyun; Yu, Kyung-Sang; Jang, In-Jin; Cho, Joo-Youn

2017-07-01

Cytochrome P450 (CYP) 3A is an important drug-metabolizing enzyme in humans. Assessing CYP3A activity is necessary for predicting therapeutic outcomes or the potential adverse events of various therapeutics. This study sought to evaluate the distribution of endogenous and exogenous markers reflecting hepatic CYP3A activity and related factors affecting its activity in healthy male and female. Each subject was given a single 1 mg dose of midazolam intravenously. Pharmacokinetics, pharmacometabolomics, and pharmacogenomics analyses were performed to evaluate CYP3A activity. Urinary and plasma steroids were quantified with gas chromatography coupled with triple-quadrupole mass spectrometry (GC-MS), and the concentrations of midazolam and its metabolites were quantified with liquid chromatography coupled with electrospray tandem mass spectrometry (LC-MS/MS). A total of 100 subjects completed this study. Midazolam clearance (MDZ CL) and the metabolic ratio (MDZ MR) were significantly correlated with 6β-OH-cortisol/cortisol and 6β-OH-cortisone/cortisone. MDZ CL, 6β-OH-cortisol/cortisol, and 6β-OH-cortisone/cortisone decreased with increasing age (Pearson r = -0.333, -0.329, and -0.528, respectively; P exogenous and endogenous markers showed decreased CYP3A activity with increasing age, which suggested that age could be a factor that significantly influences CYP3A activity.

Diurnal Hypothalamic-Pituitary-Adrenal Axis Measures and Inflammatory Marker Correlates in Major Depressive Disorder

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Kelly Doolin

2017-10-01

Full Text Available Dysregulation of the hypothalamic-pituitary-adrenal (HPA axis and inflammatory systems is a consistent finding in patients with Major Depressive Disorder (MDD. Cortisol is often assessed by measurement of the cortisol awakening response (CAR and/or diurnal cortisol levels. Some methods of cortisol measurement overestimate cortisol concentration due to detection of other glucocorticoids including the relatively inert cortisone, therefore this study aimed to assess the presence of both cortisol and cortisone, and the cortisol-cortisone catalyzing enzyme 11β-hydroxysteroiddehydrogenase type 1 (11β-HSD1, in depressed patients and controls. Because the HPA axis is known to regulate the body’s immune system, relationships between measures of cytokines and cortisol were also assessed. Saliva samples were collected from 57 MDD patients and 40 healthy controls at five post-wakening time points (0, +30, +60, +720 and +750 min. Glucocorticoid concentrations were measured by liquid chromatography mass spectrometry. Whole blood mRNA expression of several inflammatory markers was measured by quantitative polymerase chain reaction. This study replicated the common finding of elevated morning cortisol and reduced CAR reactivity in MDD and found no differences in cortisone or 11β-HSD1 mRNA measures. There was a negative association between interleukin 1-β (IL-1β mRNA and morning cortisol reactivity within the depressed group, indicating that dysregulation of the HPA axis and immune system may be interconnected.

Effects of glucocorticoid hormones on radiation induced and 12-O-tetradecanoylphorbol-13-acetate enhanced radiation transformation in vitro

International Nuclear Information System (INIS)

Kennedy, A.R.; Umans, R.S.

1988-01-01

We have studied the interactions of glucocorticoid hormones with radiation in the induction of transformation in vitro in C3AH10T1/2 cells. We have observed that cortisone has its primary enhancing effect on radiation transformation when present after the radiation exposure during the ''expression period'', or the time after carcinogen exposure during which promoting agents have been shown to enhance radiation transformation in vitro, and that two different glucocorticoid hormones, dexamethasone and cortisone, have a suppressive effect on the 12-O-tetradecanoylphorbol-13-acetate (TPA) enhancement of radiation transformation in vitro

Lack of regulation of 11β-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

2009-01-01

Objective 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 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), thereby reducing cortisol regeneration in liver and adipose tissue. We aimed to measure acute effects of GH on 11β-HSD1 in liver and adipose tissue in vivo, including using a stable isotope tracer. Design Observational studies of GH withdrawal and reintroduction in patients with hypopituitarism. Methods 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 9,11,12,12-2H4-cortisol (d4-cortisol) infusion, urinary cortisol/cortisone metabolite ratios, liver 11β-HSD1 by appearance of plasma cortisol after oral cortisone, and 11β-HSD1 mRNA levels in subcutaneous adipose biopsies. Results GH withdrawal and reintroduction had no effect on 9,12,12-[2H]3-cortisol (d3-cortisol) appearance, urinary cortisol/cortisone metabolite ratios, initial appearance of cortisol after oral cortisone, or adipose 11β-HSD1 mRNA. GH withdrawal increased plasma cortisol 30–180 min after oral cortisone, increased d4-cortisol clearance, and decreased relative excretion of 5α-reduced cortisol metabolites. Conclusions In this setting, GH did not regulate 11β-HSD1 rapidly in vivo in humans. Altered cortisol metabolism with longer term changes in GH may reflect indirect effects on 11β-HSD1. These data do not suggest that glucocorticoid replacement doses need to be increased immediately after introducing GH therapy to compensate for reduced 11β-HSD1 activity, although dose adjustment may be required in the longer term. PMID:19549748

Acute effects of 3,4-methylenedioxymethamphetamine and methylphenidate on circulating steroid levels in healthy subjects.

Science.gov (United States)

Seibert, Julia; Hysek, Cédric M; Penno, Carlos A; Schmid, Yasmin; Kratschmar, Denise V; Liechti, Matthias E; Odermatt, Alex

2014-01-01

3,4-Methylenedioxymethamphetamine (MDMA, 'ecstasy') and methylphenidate are widely used psychoactive substances. MDMA primarily enhances serotonergic neurotransmission, and methylphenidate increases dopamine but has no serotonergic effects. Both drugs also increase norepinephrine, resulting in sympathomimetic properties. Here we studied the effects of MDMA and methylphenidate on 24-hour plasma steroid profiles. 16 healthy subjects (8 men, 8 women) were treated with single doses of MDMA (125 mg), methylphenidate (60 mg), MDMA + methylphenidate, and placebo on 4 separate days using a cross-over study design. Cortisol, cortisone, corticosterone, 11-dehydrocorticosterone, aldosterone, 11-deoxycorticosterone, dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), androstenedione, and testosterone were repeatedly measured up to 24 h using liquid chromatography-tandem mass spectroscopy. MDMA significantly increased the plasma concentrations of cortisol, corticosterone, 11-dehydrocorticosterone, and 11-deoxycorticosterone and also tended to moderately increase aldosterone levels compared with placebo. MDMA also increased the sum of cortisol + cortisone and the cortisol/cortisone ratio, consistent with an increase in glucocorticoid production. MDMA did not alter the levels of cortisone, DHEA, DHEAS, androstenedione, or testosterone. Methylphenidate did not affect any of the steroid concentrations, and it did not change the effects of MDMA on circulating steroids. In summary, the serotonin releaser MDMA has acute effects on circulating steroids. These effects are not observed after stimulation of the dopamine and norepinephrine systems with methylphenidate. The present findings support the view that serotonin rather than dopamine and norepinephrine mediates the acute pharmacologically induced stimulation of the hypothalamic-pituitary-adrenal axis in the absence of other stressors. © 2014 S. Karger AG, Basel.

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

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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.

Over-the-Counter "Adrenal Support" Supplements Contain Thyroid and Steroid-Based Adrenal Hormones.

Science.gov (United States)

Akturk, Halis Kaan; Chindris, Ana Maria; Hines, Jolaine M; Singh, Ravinder J; Bernet, Victor J

2018-03-01

To assess whether dietary supplements that are herbal and/or animal-derived products, marketed for enhancing metabolism or promoting energy, "adrenal fatigue," or "adrenal support," contain thyroid or steroid hormones. Twelve dietary adrenal support supplements were purchased. Pregnenolone, androstenedione, 17-hydroxyprogesterone, cortisol, cortisone, dehydroepiandrosterone sulfate, synthetic glucocorticoids (betamethasone, dexamethasone, fludrocortisone, megestrol acetate, methylprednisolone, prednisolone, prednisone, budesonide, and triamcinolone acetonide) levels were measured twice in samples in a blinded fashion. This study was conducted between February 1, 2016, and November 1, 2016. Among steroids, pregnenolone was the most common hormone in the samples. Budesonide, 17-hydroxyprogesterone, androstenedione, cortisol, and cortisone were the others in order of prevalence. All the supplements revealed a detectable amount of triiodothyronine (T3) (63-394.9 ng/tablet), 42% contained pregnenolone (66.12-205.2 ng/tablet), 25% contained budesonide (119.5-610 ng/tablet), 17% contained androstenedione (1.27-7.25 ng/tablet), 8% contained 17-OH progesterone (30.09 ng/tablet), 8% contained cortisone (79.66 ng/tablet), and 8% contained cortisol (138.5 ng/tablet). Per label recommended doses daily exposure was up to 1322 ng for T3, 1231.2 ng for pregnenolone, 1276.4 ng for budesonide, 29 ng for androstenedione, 60.18 ng for 17-OH progesterone, 277 ng for cortisol, and 159.32 ng for cortisone. All the supplements studied contained a small amount of thyroid hormone and most contained at least 1 steroid hormone. This is the first study that measured thyroid and steroid hormones in over-the-counter dietary "adrenal support" supplements in the United States. These results may highlight potential risks of hidden ingredients in unregulated supplements. Copyright © 2017 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Positive and negative social support and HPA-axis hyperactivity: Evidence from glucocorticoids in human hair.

Science.gov (United States)

Iob, Eleonora; Kirschbaum, Clemens; Steptoe, Andrew

2018-06-12

While positive social support is associated with lower prevalence of disease and better treatment outcomes, negative social relationships can instead have unfavourable consequences for several physical and mental health conditions. However, the specific mechanisms by which this nexus might operate remain poorly understood. Hypothalamic-pituitary-adrenal (HPA) axis hyperactivity owing to psychosocial stress has been proposed as a potential pathway underlying the link between social support and health. Hair glucocorticoids such as cortisol and cortisone are emerging as promising biomarkers of long-term retrospective HPA activation. Therefore, the aim of this investigation was to examine the effects of positive and negative experiences of social support within key relationships (i.e. spouse/partner, children, other family members, and friends) on cortisol and cortisone. These associations were tested in a sample of 2520 older adults (mean age 68.1) from the English Longitudinal Study of Ageing. Hair samples were collected in wave 6 (2012/13). To understand the impact of cumulative exposure to poor social support, the analysis used self-reported data from waves 4 (2008/09) and 6. Covariates included demographic, socioeconomic, lifestyle, and hair characteristics. In cross sectional analyses, lower positive support from all sources and specifically from children were associated with higher cortisol. Additionally, lower positive support from children was positively associated with cortisone. Similarly, higher overall negative support was related to higher cortisol, and greater negative support from children was also positively associated with cortisone. In longitudinal analyses, there was evidence for positive associations between hair glucocorticoids and cumulative exposure to poorer social support. Experiences of low positive and high negative social support, particularly from children, were both related to higher hair glucocorticoids. Hence, social relationships of

Allgrove′s syndrome: Case report and literature review

Directory of Open Access Journals (Sweden)

Mohamed I Yasawy

2009-01-01

Glucocorticoid therapy was initiated. The management consisted of pneumatic cardiac dilatation and initiation of cortisone treatment. The patients′ response was impressive and they resumed most of their usual activities.

Disease: H00603 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available pertension caused by the activating S810L mutation in the mineralocorticoid receptor is cortisone related. ... JOURNAL ... Endocrinology 144:528-33 (2003) DOI:10.1210/en.2002-220708

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.

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.

What is Psoriasis? | NIH MedlinePlus the Magazine

Science.gov (United States)

... Sometimes psoriasis will appear after a cut, scratch, sunburn, or an infection. How Does Psoriasis Affect Quality ... the skin may be a reaction to severe sunburn or to taking cortisone or other medicines. It ...

275 THE AETIOLOGY AND POSSmLE PREVENTION OF ...

African Journals Online (AJOL)

1971-03-13

Mar 13, 1971 ... sex hormones, vitamin D3 and cortisone, suggests that future research ... Nevertheless, the importance of these various characteristics and, in fact, ..... As in idiopathic hypercalcaemia, high doses of vitamin D can also cause ...

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 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.

Deep Friction Massage Versus Steroid Injection in the Treatment of Lateral Epicondylitis.

Science.gov (United States)

Yi, Rosemary; Bratchenko, Walter W; Tan, Virak

2018-01-01

The aim of the study was to determine the efficacy of deep friction massage in the treatment of lateral epicondylitis by comparing outcomes with a control group treated with splinting and therapy and with an experimental group receiving a local steroid injection. A randomized clinical trial was conducted to compare outcomes after recruitment of consecutive patients presenting with lateral epicondylitis. Patients were randomized to receive one of 3 treatments: group 1: splinting and stretching, group 2: a cortisone injection, or group 3: a lidocaine injection with deep friction massage. Pretreatment and posttreatment parameters of visual analog scale (VAS) pain ratings, Disabilities of the Arm, Shoulder and Hand (DASH) scores, and grip strength were measured. Outcomes were measured at early follow-up (6-12 weeks) and at 6-month follow-up. There was a significant improvement in VAS pain score in all treatment groups at early follow-up. DASH score and grip strength improved in the cortisone injection group and the deep friction massage group at early follow-up; these parameters did not improve in the splinting and stretching group. At 6-month follow-up, only patients in the deep friction massage group demonstrated a significant improvement in all outcome measures, including VAS pain score, DASH score, and grip strength. Deep friction massage is an effective treatment for lateral epicondylitis and can be used in patients who have failed other nonoperative treatments, including cortisone injection.

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

International Nuclear Information System (INIS)

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

1986-01-01

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 [ 35 S]heparin or [ 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

Radioimmunoassay reagent and its use in a radioimmunoassay

International Nuclear Information System (INIS)

Polito, A.J.; Knight, W.S.

1977-01-01

A radioimmunoassay to detect or determine a steroid of the cortisone and aldosterone group has been developed. The invention particularly concerns a steroid derivative containing imidazole group which is radioactively labelled. The invented reagents are labelled with iodine 125. (VJ) [de

Questions and Answers About Shoulder Problems

Science.gov (United States)

... injury. Injection of a cortisone medicine into your shoulder joint. Surgery to repair the tear if you don’t ... TENS). Injection of a corticosteroid drug if your shoulder is not better. Surgery if the shoulder does not improve with other ...

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

Liver polyribosome distribution in intact and adrenalectomized rats exposed to. gamma. radiation

Energy Technology Data Exchange (ETDEWEB)

Yatvin, M B; Abdel-Halim, M N [Wisconsin Univ., Madison (USA). Dept. of Radiology; Wisconsin Univ., Madison (USA). Dept. of Human Oncology)

1978-06-01

The mechanism(s) by which gamma radiation influences liver polyribosome distribution was studied in groups of intact and adrenalectomized male rats. A shift from light to heavy aggregates occurred in the polyribosomes of both intact and adrenalectomized rats after they were exposed to gamma rays. In irradiated adrenalectomized rats, however, the shift to heavier aggregates was not as great as that which occurred in irradiated adrenal-intact animals. Subcutaneous injection of cortisone acetate (10 mg/100 g body weight) also altered the liver polyribosome patterns of both intact and adrenalectomized rats within 8 hours of its administration. The shift which occurred following cortisone administration, however, was less striking than that seen after irradiation only. Thus, although adrenal glucocorticoids contribute to the radiation-indu ied shift in liver polyribosomes in adrenal-intact rats, other factors appear to be involved, since the shift is also obtained in adrenalectomized animals.

Hair cortisol and cortisol awakening response are associated with criteria of the metabolic syndrome in opposite directions.

Science.gov (United States)

Kuehl, Linn K; Hinkelmann, Kim; Muhtz, Christoph; Dettenborn, Lucia; Wingenfeld, Katja; Spitzer, Carsten; Kirschbaum, Clemens; Wiedemann, Klaus; Otte, Christian

2015-01-01

Findings on the association between hypothalamic-pituitary-adrenal (HPA) axis activity and metabolic risk are equivocal. Different methods of measuring HPA activity might indicate adverse vs. beneficial effects of HPA activity on metabolic risk thus contributing to heterogenous findings. In this study, we aimed to determine whether (1) the salivary cortisol awakening response (CAR) as a marker of awakening-induced activation of the HPA axis and (2) hair cortisol as a marker of long-term cortisol secretion are associated with criteria of the metabolic syndrome. Therefore, we recruited 41 healthy individuals (26 women, mean age: 41.2 years) and 44 patients with major depression (28 women, 41.4 years) and assessed CAR and hair cortisol values as well as all criteria of the metabolic syndrome (abdominal obesity, blood pressure, plasma glucose, triglycerides and high-density cholesterol levels) according to the International Diabetes Federation. CAR and hair cortisol values were divided into tertiles. Across groups, participants with hair cortisol or hair cortisone in the highest tertile showed significantly more criteria of the metabolic syndrome compared to participants in the medium or low tertile (F2,64=3.37, p=.04). These results were corroborated by significant positive correlations between mean hair cortisol values with waist circumference (r=.29, p=.03), triglycerides (r=.34, p=.01) and systolic blood pressure (r=.29, p=.04) and between mean hair cortisone and triglycerides (r=.46, pcortisol and hair cortisone levels but lower CAR values are associated with an unfavorable metabolic and cardiovascular risk profile. Copyright © 2014 Elsevier Ltd. All rights reserved.

Cryptococcal Meningitis | van den Ende | South African Medical ...

African Journals Online (AJOL)

Cryptococcal meningitis occurred in an elderly Coloured woman in the Northern Cape. She presented with symptoms and signs suggestive of encephalitis 4 weeks after a cholecystectomy. After the administration of cortisone, cryptococcal organisms were isolated in her cerebrospinal fluid. She was first treated with ...

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...

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.

Cryptococcal Meningitis

African Journals Online (AJOL)

1974-03-16

Mar 16, 1974 ... Cryptococcal meningitis occurred in an elderly Coloured woman in the Northern Cape. She presented with symp- toms and signs suggestive of encephalitis 4 weeks after a cholecystectomy. After the administration of cortisone, cryptococcal organisms were isolated in her cerebrospinal fluid. She was first ...

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

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

International Nuclear Information System (INIS)

Goguev, N.T.

1985-01-01

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

Disease: H01111 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available . 11beta-HSD1 is a dimeric enzyme that catalyzes the reduction of cortisone to cortisol within the endoplasm...ed metabolic disease; Endocrine disease H6PD [HSA:9563] [KO:K13937] HSD11B1 [HSA:3290] [KO:K15680] ... Extremely low ratio of cortisol

A Comparison of Salivary Steroid Levels during Diagnostic Tests for Adrenal Insufficiency

Directory of Open Access Journals (Sweden)

Michaela Dušková

2016-01-01

Full Text Available Numerous diagnostic tests are used to evaluate the hypothalamic-pituitary-adrenal axis (HPA axis. The gold standard is still considered the insulin tolerance test (ITT, but this test has many limitations. Current guidelines therefore recommend the Synacthen test first when an HPA axis insufficiency is suspected. However, the dose of Synacthen that is diagnostically most accurate and sensitive is still a matter of debate. We investigated 15 healthy men with mean/median age 27.4/26 (SD ±4.8 years, and mean/median BMI (body mass index 25.38/24.82 (SD ±3.2 kg/m2. All subjects underwent 4 dynamic tests of the HPA axis, specifically 1 μg, 10 μg, and 250 μg Synacthen (ACTH tests and an ITT. Salivary cortisol, cortisone, pregnenolone, and DHEA (dehydroepiandrosterone were analysed using liquid chromatography-tandem mass spectrometry. During the ITT maximum salivary cortisol levels over 12.5 nmol/l were found at 60 minutes. Maximum cortisol levels in all of the Synacthen tests were higher than this; however, demonstrating that sufficient stimulation of the adrenal glands was achieved. Cortisone reacted similarly as cortisol, i.e. we did not find any change in the ratio of cortisol to cortisone. Pregnenolone and DHEA were higher during the ITT, and their peaks preceded the cortisol peak. There was no increase of pregnenolone or DHEA in any of the Synacthen tests. We demonstrate that the 10 μg Synacthen dose is sufficient stimulus for testing the HPA axis and is also a safe and cost-effective alternative. This dose also largely eliminates both false negative and false positive results.

Long-term glucocorticoid concentrations as a risk factor for childhood obesity and adverse body-fat distribution.

Science.gov (United States)

Noppe, G; van den Akker, E L T; de Rijke, Y B; Koper, J W; Jaddoe, V W; van Rossum, E F C

2016-10-01

Childhood obesity is an important risk factor for premature development of the metabolic syndrome (MetS) at adulthood. There is need for understanding of the mechanisms underlying the MetS and obesity. Patients with Cushing's disease suffer from similar metabolic complications, leading to the hypothesis that inter-individual cortisol variation may contribute to the onset of obesity. In addition, glucocorticoid receptor (GR)-gene polymorphisms resulting in differential glucocorticoid (GC) sensitivity, have been associated with an adverse metabolic profile. To study associations of GC levels in scalp hair, as a marker of long-term systemic GC concentrations, and genetically determined GC sensitivity with obesity and body-fat distribution in children. We performed a cross-sectional study of cortisol and cortisone concentrations over a 3-month period, measured by LC-MS/MS (Liquid Chromatography Tandem Mass Spectrometry) in hair of 3019 6-year-old children participating in the Generation R study. Genotyping of GR-gene polymorphisms was performed. Of all children, 4.3% was obese and 13.4% overweight. Cortisol was significantly associated with risk of obesity (odd ratio (OR): 9.4 (3.3-26.9)) and overweight (OR: 1.4 (1.0-2.0)). Cortisone was associated with risk of obesity (OR: 1.9 (1.0-3.5)). Cortisol and cortisone were significantly positively associated with body mass index, fat mass (FM) index and android/gynecoid FM ratio. GR polymorphisms were not associated with adiposity parameters. Long-term cortisol concentrations are strongly associated with an increased risk of childhood obesity and adverse body-fat distribution. Future research may reveal whether these are causal relations and may be a target for therapy.

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African Journals Online (AJOL)

Unregulated antibiotic use and rampant practice of self-medication in Nigeria, is a cause for concern. Methods: A total of ... crobiota by the administration of antibiotics, cortisone medication .... jectives with the condenser iris closed sufficiently to give good contrast. ... Using a sterile wire loop, a colony of each suspected Can-.

Determination of steroid hormones and their metabolite in several types of meat samples by ultra high performance liquid chromatography-Orbitrap high resolution mass spectrometry.

Science.gov (United States)

López-García, Marina; Romero-González, Roberto; Garrido Frenich, Antonia

2018-03-09

A new analytical method based on ultra-high performance liquid chromatography (UHPLC) coupled to Orbitrap high resolution mass spectrometry (Orbitrap-HRMS) has been developed for the determination of steroid hormones (hydrocortisone, cortisone, progesterone, prednisone, prednisolone, testosterone, melengesterol acetate, hydrocortisone-21-acetate, cortisone-21-acetate, testosterone propionate, 17α-methyltestosterone, 6α-methylprednisolone and medroxyprogesterone) and their metabolite (17α-hydroxyprogesterone) in three meat samples (chicken, pork and beef). Two different extraction approaches were tested (QuEChERS "quick, easy, cheap, effective, rugged and safe" and "dilute and shoot"), observing that the QuEChERS method provided the best results in terms of recovery. A clean-up step was applied comparing several sorbents, obtaining the best results when florisil and aluminum oxide were used. The optimized method was validated, obtaining suitable results for all validation parameters in the three meat matrices evaluated. Recovery values ranged from 70% to 103% (except for prednisone in beef samples), meanwhile repeatability and reproducibility were obtained at values lower than 18% and 21%, respectively. The limit of quantification (LOQ) was established for most of the compounds at 1.0 μg/kg, except for testosterone in chicken and hydrocortisone-21-acetate and cortisone-21-acetate in pork at 2.0 μg/kg. Decision limit (CCα) and detection capability (CCβ) values ranged from 1.0-2.7 μg/kg and 1.9-5.5 μg/kg, respectively, in the three matrices. Finally, thirty one meat samples were analyzed and two hormones, progesterone and hydrocortisone, were detected in a beef and pork sample at 1.7 and 2.8 μg/kg respectively. Copyright © 2018 Elsevier B.V. All rights reserved.

Effects of Carbenoxolone on the Canine Pituitary-Adrenal Axis.

Science.gov (United States)

Teshima, Takahiro; Matsumoto, Hirotaka; Okusa, Tomoko; Nakamura, Yumi; Koyama, Hidekazu

2015-01-01

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.

Fatigue During Head-And-Neck Radiotherapy: Prospective Study on 117 Consecutive Patients

International Nuclear Information System (INIS)

Jereczek-Fossa, Barbara Alicja; Santoro, Luigi; Alterio, Daniela; Franchi, Benedetta; Fiore, Maria Rosaria; Fossati, Piero; Kowalczyk, Anna; Canino, Paola; Ansarin, Mohssen; Orecchia, Roberto

2007-01-01

Purpose: Fatigue is an underevaluated cancer-related and treatment-related symptom. We analyzed fatigue in head and neck cancer patients undergoing radiotherapy (RT). Methods and Materials: A total of 117 patients were enrolled (mean age, 58 years). Radiation therapy (median dose, 66 Gy) was given with either exclusive or postoperative intent in 52 and 65 patients, respectively. Chemotherapy (CT) was added before and/or during RT in 61 patients. The patients completed a 20-item questionnaire (Multidimensional Fatigue Inventory [MFI-20]) before, during (weekly), and after RT. The impact of patient-, tumor-, and treatment-related factors on fatigue was evaluated with unifactorial and multifactorial tests. Results: Fatigue level increased during RT reaching a maximum at Week 6 and then slowly decreased. In multivariate stepwise regression analysis age (inversely related, p < 0.05), psychologic disorders (p < 0.005), and previous head-and-neck surgery (inversely related, p < 0.005) were correlated with higher pre-RT fatigue level. Pre-RT fatigue score (p < 0.0001), induction and/or concomitant CT (p = 0.035), need of cortisone during RT (p = 0.005), and thyroid disorders (p = 0.032) were correlated with higher during-RT fatigue level. Pre-RT fatigue score (p < 0.0001), induction and/or concomitant CT (p < 0.001), and need of cortisone during RT (p < 0.005) were correlated with higher post-RT fatigue level. No impact of gender, performance status, comorbidities other than psychologic and thyroid, tumor stage/site, RT intent, dose, volume, duration, or toxicity was observed. Conclusion: Fatigue affects all patients undergoing RT for head-and-neck cancer, reaches maximum score at the 6th week of RT, and slowly decreases thereafter. Age, thyroid dysfunction, psychologic disorders, pre-RT fatigue score, CT, and cortisone use are correlated with RT-related fatigue levels

Vindesine in plasma cell tumors.

Science.gov (United States)

Salvagno, L; Paccagnella, A; Chiarion Sileni, V; De Besi, P; Frizzarin, M; Casara, D; Fiorentino, M V

1985-12-31

Twenty-one patients with plasma cell tumors received vindesine (VDS) at the dose of 3 mg/m2 i.v. on day 1 plus prednisone at the dose of 100 mg p.o. from day 1 to 5, recycling every 8 days 3 times and then every 10-12 days. In 3 patients with gastric or duodenal ulcer prednisone was not administered. All but one patient were heavily pretreated and resistant to M-2 regimen. Overall there were 4 objective responses (19%): 2 among 15 patients (13%) with multiple myeloma and 2 among 6 patients (33%) with extramedullary plasmacytoma (EMP). The responses lasted for 2, 12, 15 and 48+ months. One previously untreated EMP patient received VDS without prednisone and obtained a complete long-lasting remission. The association of VDS with high-dose prednisone seems to have some activity in plasma cell tumors; probably in multiple myeloma the objective responses are due to the high dose of cortisone rather than to VDS. On the contrary, in EMP patients, VDS may be an active agent, even if administered without cortisone.

Prophylaxis of radiation dermatitis with a topical cortisone cream

International Nuclear Information System (INIS)

Potera, M.E.; Lookingbill, D.P.; Stryker, J.A.

1982-01-01

Nineteen cancer patients receiving radiation therapy to the head, neck, chest wall, or abdomen were evaluated in a double-blind study to determine the effectiveness of 0.2% hydrocortisone valerate vs. placebo in reducing acute radiation dermatitis. Patients applied hydrocortisone valerate to one-half of the irradiated area and the placebo to the other half beginning two weeks after the initiation of radiotherapy and continuing until three weeks after completion. Left and right sides were scored each week with respect to erythema, dry desquamation, moist desquamation, ulceration, and the duration and intensity of symptoms such as soreness, burning, and itching. No statistically significant difference was found between the 0.2% hydrocortisone valerate and the placebo in the acute skin response or the symptoms of radiation dermatitis. The patients were evaluated three months following radiotherapy for evidence of skin atrophy. There were no differences found between hydrocortisone valerate and the placebo with respect to the late effects of radiation therapy

The clearance of liposomes administered by the intramuscular route

International Nuclear Information System (INIS)

Arrowsmith, M.; Mills, S.N.

1982-01-01

Iodine 131-labelled lecithin was used to label liposomes entrapping cortisone-21-palmitate. The lecithin was injected into the fascia latae muscles of rabbits and the percentage of the initial dose remaining at certain time intervals was calculated from gamma camera image data. Release from the intramuscular site occurs by diffusion from intact liposomes. (U.K.)

Cortisol suppresses radiation transformation in vitro

International Nuclear Information System (INIS)

Kennedy, A.R.

1985-01-01

It is reported that 10 -7 M cortisol has a significant suppressive effect on radiation-induced transformation in vitro in C3H10T 1/2 cells. Previously reported data showed a significant enhancing effect for similar experiments performed with cortisone. Thus, these two structurally similar glucocorticoid hormones have opposite effects on transformation induced by ionizing radiation. (author)

CT scans in studies of the dynamics of liposynthesis and lipolysis of the human liver

International Nuclear Information System (INIS)

Huebener, K.H.; Schmitt, W.G.H.

1981-01-01

Following an analysis of the most important metabolic disturbances and other diseases associated ith fatty degeneration of the liver, it is shown, basing on a previous study, by means of examples, that subtle diagnosis of changes of the fatty content of the liver can be achieved via CT density measurement. Lipolysis in alcoholic fatty liver is quantified during abstention from alcohol, and a lipolysis factor of 1% fatty decomposition per day is determined from the measurements. Observations in pancreatitis with liver lipid storage during the course of the disease, point to an enzymatic weakness in lipid metabolism. Case histories show fatty degeneration associated with an enhanced cortisone serum level (in adrenal adenoma and cortisone therapy) and in poorly stabilized diabetes mellitus. It is concluded from the studies that determination of the relative fatty content by CT densitometry should be conducted as a routine procedure and that pathological lipid content should stimulate subtle diagnosis of the pancreas and the adrenals. In addition, examinations repeated during the course of the disease with assessment of changes in fatty content, will be useful for assessing the value of the therapy employed. (orig.) [de

Targeting the pre-receptor metabolism of cortisol as a novel therapy in obesity and diabetes.

Science.gov (United States)

Gathercole, Laura L; Stewart, Paul M

2010-10-01

Due to its impact upon health and the economy, the mechanisms that contribute to the pathogenesis of obesity and the metabolic syndrome are under intense scrutiny. In addition to understanding the pathogenesis of disease it is important to design and trial novel therapies. Patients with cortisol excess, Cushing's syndrome, have a phenotype similar to that of the metabolic syndrome and as a result there is much interest the manipulation of glucocorticoid (GC) action as a therapeutic strategy. Intracellular GC levels are regulated by 11β-hydroxysteroid dehydrogenase (11β-HSD1) which converts inactive cortisone to cortisol, thereby increasing local GC action. There is an abundance of data implicating 11β-HSD1 in the pathogenesis of obesity, type 2 diabetes and the metabolic syndrome and 11β-HSD1 is an attractive therapeutic target. Selective 11β-HSD1 inhibitors, which do not act upon 11β-HSD2 (which inactivates cortisol to cortisone) are in development. So far studies have primarily been carried out in rodents, with results showing improvements in metabolic profile. Data are now beginning to emerge from human studies and the results are promising. Copyright © 2010 Elsevier Ltd. All rights reserved.

CT scans in studies of the dynamics of liposynthesis and lipolysis of the human liver

Energy Technology Data Exchange (ETDEWEB)

Huebener, K H; Schmitt, W G.H.

1981-06-01

Following an analysis of the most important metabolic disturbances and other diseases associated with fatty degeneration of the liver, it is shown, basing on a previous study, by means of examples, that subtle diagnosis of changes of the fatty content of the liver can be achieved via CT density measurement. Lipolysis in alcoholic fatty liver is quantified during abstention from alcohol, and a lipolysis factor of 1% fatty decomposition per day is determined from the measurements. Observations in pancreatitis with liver lipid storage during the course of the disease, point to an enzymatic weakness in lipid metabolism. Case histories show fatty degeneration associated with an enhanced cortisone serum level (in adrenal adenoma and cortisone therapy) and in poorly stabilized diabetes mellitus. It is concluded from the studies that determination of the relative fatty content by CT densitometry should be conducted as a routine procedure and that pathological lipid content should stimulate subtle diagnosis of the pancreas and the adrenals. In addition, examinations repeated during the course of the disease with assessment of changes in fatty content, will be useful for assessing the value of the therapy employed.

Septic monoarthritis of the first carpo-metacarpal joint caused by Mycobacterium kansasii.

Science.gov (United States)

Brutus, J P; Lamraski, G; Zirak, C; Hauzeur, J P; Thys, J P; Schuind, F

2005-02-01

A case of septic carpal monoarthritis due to Mycobacterium kansasii developing 16 months after accidental inoculation in a healthy laboratory technician is reported. No predisposing factor such as immunosuppression, preexisting degenerative, inflammatory arthritis or cortisone injection was present. Treatment with antituberculous oral medication alone resulted in resolution of the disease. Synovectomy was unnecessary. Ten years after the initial causative event, the patient remains free of symptoms.

Socioeconomic status in children is associated with hair cortisol levels as a biological measure of chronic stress.

Science.gov (United States)

Vliegenthart, J; Noppe, G; van Rossum, E F C; Koper, J W; Raat, H; van den Akker, E L T

2016-03-01

Low socioeconomic status (SES) may be associated with a high risk of lifestyle-related diseases such as cardiovascular diseases. There is a strong association between parental SES, stress and indicators of child health and adult health outcome. The exact mechanisms underlying this association have not yet been fully clarified. Low SES may be associated with chronic stress, which may lead to activation of the hypothalamic-pituitary-adrenal (HPA)-axis, resulting in a higher circulating level of the stress hormone cortisol. Therefore, chronic stress may mediate the association between low SES and elevated cortisol levels and its adverse outcomes. We investigated whether SES was associated with a chronic measure of cortisol exposure in a child population. Cortisol and cortisone were measured in scalp hair in 270 children and adolescents, aged 4-18 years, enrolled through school visits. Neighborhood level SES was based on a score developed by the Netherlands Institute for Social Research using postal codes, and this includes neighborhood measures of income education and unemployment. Maternal and paternal education level were used as indicators of family SES. Neighborhood level socioeconomic status score was significantly associated with hair cortisol (β=-0.103, p=0.007, 95%CI [-0.179, -0.028]) and hair cortisone (β=-0.091, p=0.023, 95%CI [-0.167, -0.015]), adjusted for age and sex. Additionally, hair cortisol was significantly correlated with maternal education level and hair cortisone was significantly correlated with paternal education level. The results of our study suggest that the widely shown association between low family SES and adverse child health outcomes may be mediated by chronic stress, given the chronically higher levels of cortisol in children and adolescents in families with low SES. It is especially notable that the association between SES and cortisol was already found in children of young age as this can have major consequences, such as increased

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

[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.

Mineralocorticoid hypertension and hypokalaemia induced by posaconazole

OpenAIRE

Boughton, Charlotte; Taylor, David; Ghataore, Lea; Taylor, Norman; Whitelaw, Benjamin C

2018-01-01

Summary We describe severe hypokalaemia and hypertension due to a mineralocorticoid effect in a patient with myelodysplastic syndrome taking posaconazole as antifungal prophylaxis. Two distinct mechanisms due to posaconazole are identified: inhibition of 11β hydroxylase leading to the accumulation of the mineralocorticoid hormone 11-deoxycorticosterone (DOC) and secondly, inhibition of 11β hydroxysteroid dehydrogenase type 2 (11βHSD2), as demonstrated by an elevated serum cortisol-to-cortison...

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.

Late effects of selected immunosuppressants on immunocompetence, disease incidence, and mean life-span. III. Disease incidence and life expectancy. [Mice, x radiation

Energy Technology Data Exchange (ETDEWEB)

Peter, C P; Perkins, E H; Peterson, W J; Walburg, H E; Makinodan, T

1975-01-01

The effect of various immunosuppressive treatments on mean life-span and disease incidence have been studied. Significant life shortening was seen only in mice which received X-irradiation early in life and can be ascribed primarily to an increased incidence of certain malignancies. Marginal life shortening was seen in cyclophosphamide-treated animals, however, survival patterns between those and control animals did not differ until 30 months of age and the magnitude of life-shortening never approached that seen in X-irradiated animals. Thymectomy, splenectomy or cortisone treatment did not alter survival. All immunosuppressive treatments enhanced mortality due to non-neoplastic diseases, however, only a small percentage of animals die with these disease entities. With the exception of cortisone all immunosuppressive treatments increased the incidence of neoplastic disease. However, their effects on various neoplastic processes were variable and unpredictable. Four primary patterns in terms of relative immune competence, disease incidence and life expectancy were seen. Thus, immunodepression may or may not correlate with increased disease incidence, which in turn may or may not have a life-shortening effect. These findings are discussed in terms of the marked reduction of both humoral and cell-mediated immunity normally seen in aged mice and the significance of postulated immune surveillance mechanisms to survival.

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.

Autologous Blood Injection and Wrist Immobilisation for Chronic Lateral Epicondylitis

Science.gov (United States)

Massy-Westropp, Nicola; Simmonds, Stuart; Caragianis, Suzanne; Potter, Andrew

2012-01-01

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. PMID:23251809

Stress hormones predict hyperbolic time-discount rates six months later in adults.

Science.gov (United States)

Takahashi, Taiki; Shinada, Mizuho; Inukai, Keigo; Tanida, Shigehito; Takahashi, Chisato; Mifune, Nobuhiro; Takagishi, Haruto; Horita, Yutaka; Hashimoto, Hirofumi; Yokota, Kunihiro; Kameda, Tatsuya; Yamagishi, Toshio

2010-01-01

Stress hormones have been associated with temporal discounting. Although time-discount rate is shown to be stable over a long term, no study to date examines whether individual differences in stress hormones could predict individuals' time-discount rates in the relatively distant future (e.g., six month later), which is of interest in neuroeconomics of stress-addiction association. We assessed 87 participants' salivary stress hormone (cortisol, cortisone, and alpha-amylase) levels and hyperbolic discounting of delayed rewards consisting of three magnitudes, at the time-interval of six months. For salivary steroid assays, we employed a liquid chromatography/ mass spectroscopy (LC/MS) method. The correlations between the stress hormone levels and time-discount rates were examined. We observed that salivary alpha-amylase (sAA) levels were negatively associated with time-discount rates in never-smokers. Notably, salivary levels of stress steroids (i.e., cortisol and cortisone) negatively and positively related to time-discount rates in men and women, respectively, in never-smokers. Ever-smokers' discount rates were not predicted from these stress hormone levels. Individual differences in stress hormone levels predict impulsivity in temporal discounting in the future. There are sex differences in the effect of stress steroids on temporal discounting; while there was no sex defference in the relationship between sAA and temporal discounting.

Sexual dimorphism of cortisol metabolism is maintained in elderly subjects and is not oestrogen dependent.

Science.gov (United States)

Toogood, A A; Taylor, N F; Shalet, S M; Monson, J P

2000-01-01

The net interconversion of inactive cortisone to active cortisol by 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1) may determine hepatic and adipose tissue exposure to glucocorticoid action. Cortisol metabolism exhibits a sexual dimorphism with an apparently lower activity of 11betaHSD1 in females that, in an animal model, has been attributed to the effects of oestrogen. The aim of this study is to determine whether the sexual dimorphism of cortisol metabolism persists between post-menopausal, oestrogen-deficient women and elderly men. Fifteen healthy men, aged 60.8-82.0 years, and 7 healthy women, aged 62.4-87.5 years, were studied. None of the subjects was receiving steroid medication at the time of the study. All the women were post-menopausal and none was receiving sex steroid replacement therapy. 24-h urine collections were taken from each patient and assayed for steroid metabolites by gas chromatography. Body composition was determined by dual energy X-ray absorptiometry. Blood was drawn, after an overnight fast, for the determination of serum IGF-I and IGFBP1 levels. The ratio of 11-hydroxy cortisol metabolites to 11-oxo cortisol metabolites (Fm/Em) was significantly higher in men than in women, 0.80 (0.55-1.86) vs. 0.67 (0.46-0.98) (P cortisol and cortisone metabolite (Fm/Em) and total fat mass approached significance, r = - 0.39 (P = 0.07). These relationships were not apparent in the women when considered alone. Among the men there were negative relationships between Fm/Em and total fat mass, r = - 0.48, and Fm/Em and trunk fat mass, r = - 0.48 which approached significance (both P = 0.07). Serum IGFBP-1 levels were not significantly different between the two sexes. There was a significant correlation between IGFBP-1 and Fm/Em in the men, r = 0. 84 (P sexual dimorphism in cortisol metabolism is not dependent on oestrogen, although the possibility that oestrogen exerts a permanent modifying effect on 11beta-HSD1 gene expression during the pre

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

International Nuclear Information System (INIS)

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

1982-01-01

The late gestational age rhesus monkey was used to study the transplacental pharmacokinetics of radiolabeled triamcinolone acetonide (TAC) and cortisol. Tritiated-TAC and [ 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 3 H in the fetal circulation was parent TAC, whereas only 14 to 49% of the 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 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

Androgen Metabolism in Progression to Androgen-Independent Prostate Cancer

Science.gov (United States)

2011-06-01

described CRPC bone marrow metastases (8), we detected TMPRSS2:ERG transcripts (TMPRSS2 exon 2-ERG exon 4) in 11 of 29 cases. Affymetrix oligonucleotide...and immunoblotted. B, RT-PCR for ERG ( exon 9/10), TMPRSS2 ( exon 5/6), and PSA mRNA after DHT stimulation. C, cells in CSS medium treated with DHT and...therapeutic index CYP3A4 sub- strates were excluded. The treatment was ketoconazole 400 mg orally thrice daily, hydro- cortisone (30 mg/AM and 10 mg/PM

Cytogenetic effects of chemotherapy and cranial irradiation on the peripheral blood lymphocytes of children with malignant disease

Energy Technology Data Exchange (ETDEWEB)

Fischer, P; Vetterlein, M; Pohl-Rueling, J; Krepler, P

1977-01-01

Results of a cytogenetic analysis of peripheral blood lymphocytes of children with leukemia after massive chemotherapy and cranial irradiation, and of children with nephrosis after cortisone therapy and cyclophosphamide are presented. Prolonged intensive chemotherapy results in a significant rise in the number of chromatid aberrations after twelve months, and of chromosomal aberrations after 24 months of therapy. After cranial irradiation a sharp rise in chromosome aberrations is present for about three months. This drops after one year to levels present in cases with chemotherapy alone.

Risk of classical Kaposi sarcoma by plasma levels of Epstein-Barr virus antibodies, sCD26, sCD23 and sCD30

Directory of Open Access Journals (Sweden)

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.

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.

Interaction of glucocorticoids and progesterone derivatives with human serum albumin.

Science.gov (United States)

Abboud, Rola; Akil, Mohammad; Charcosset, Catherine; Greige-Gerges, Hélène

2017-10-01

Glucocorticoids (GCs) and progesterone derivatives (PGDs) are steroid hormones with well-known biological activities. Their interaction with human serum albumin (HSA) may control their distribution. Their binding to albumin is poorly studied in literature. This paper deals with the interaction of a series of GCs (cortisol, cortisone, prednisolone, prednisone, 6-methylprednisolone and 9-fluorocortisol acetate) and PGDs (progesterone, hydroxylated PGDs, methylated PGDs and dydrogesterone) with HSA solution (pH 7.4) at molar ratios steroid to HSA varying from 0 to 10. Similar titrations were conducted using Trp aqueous solution. Fluorescence titration method and Fourier transform infrared spectroscopy (FTIR) are used. PGDs (except dydrogesterone), cortisone and 9-fluorocortisol acetate affected weakly the fluorescence of Trp in buffer solution while they decreased in a dose-dependent manner that of HSA. Their binding constants to HSA were then calculated. Moreover, displacement experiment was performed using bilirubin as a site marker. The binding constant of bilirubin to albumin was determined in the absence and presence of a steroid at a molar ratio steroid to HSA of 1. The results indicate that the steroids bind to HSA at site I in a pocket different from that of bilirubin. Furthermore, the peak positions of amide I and amide II bands of HSA were shifted in the presence of progesterone, dydrogesterone and GCs. Also a variation was observed in amide I region indicating the formation of hydrogen bonding between albumin and steroids. Copyright © 2017 Elsevier B.V. All rights reserved.

Stability of Cortisol and Cortisone in Human Breast Milk During Holder Pasteurization

NARCIS (Netherlands)

van der Voorn, Bibian; de Waard, Marita; Dijkstra, Lisette R.; Heijboer, Annemieke C.; Rotteveel, Joost; van Goudoever, Johannes B.; Finken, Martijn J. J.

2017-01-01

Human donor milk is the feeding of choice for preterm infants, when own mother's milk is not available. Holder pasteurization is necessary to secure the safety of donor milk, although it can affect milk quality by reduction of nutritional and bioactive components. Recently, research has focused on

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

receptor was located in the cytoplasm of glomerulosa and outer fasciculata cells. The intensity of the reaction product decreased in the fasciculata, and no staining was seen in inner fasciculata and reticularis. Inhibition with the simple sugars, mannose and GlcNAc confirmed a lectin-like reaction...... 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...

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...... resembling a TH1-like response. On the basis of these results it is suggested that ginseng may have the potential to be a promising natural medicine, in conjunction with other forms of treatment, for CF patients with chronic P. aeruginosa lung infection....

Thiazolopyridines Improve Adipocyte Function by Inhibiting 11 Beta-HSD1 Oxoreductase Activity

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Thirumurugan Rathinasabapathy

2017-01-01

Full Text Available Background. Glucocorticoid excess has been linked to clinical observations associated with the pathophysiology of metabolic syndrome. The intracellular glucocorticoid levels are primarily modulated by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1 enzyme that is highly expressed in key metabolic tissues including fat, liver, and the central nervous system. Methods. In this study we synthesized a set of novel tetrahydrothiazolopyridine derivatives, TR-01–4, that specifically target 11β-HSD1 and studied their ability to interfere with the glucocorticoid and lipid metabolism in the 3T3-L1 adipocytes. Results. Based on the docking model and structure-activity relationships, tetrahydrothiazolopyridine derivatives TR-02 and TR-04 showed the highest potency against 11β-HSD1 by dose-dependently inhibiting conversion of cortisone to cortisol (IC50 values of 1.8 μM and 0.095 μM, resp.. Incubation of fat cells with 0.1–10 μM TR-01–4 significantly decreased cortisone-induced lipid accumulation in adipocytes and suppressed 11β-HSD1 mRNA expression. Observed reduction in adipocyte fat stores could be partially explained by decreased expression levels of adipogenic markers (PPAR-γ, aP2 and key enzymes of lipid metabolism, including fatty acid synthase (FAS, hormone sensitive lipase (HSL, and lipoprotein lipase (LPL. Conclusions. The tetrahydrothiazolopyridine moiety served as an active pharmacophore for inhibiting 11β-HSD1 and offered a novel therapeutic strategy to ameliorate metabolic alterations found in obesity and diabetes.

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.

The Association of Prenatal Exposure to Perfluorinated Chemicals with Glucocorticoid and Androgenic Hormones in Cord Blood Samples: The Hokkaido Study.

Science.gov (United States)

Goudarzi, Houman; Araki, Atsuko; Itoh, Sachiko; Sasaki, Seiko; Miyashita, Chihiro; Mitsui, Takahiko; Nakazawa, Hiroyuki; Nonomura, Katsuya; Kishi, Reiko

2017-01-01

Perfluorinated chemicals (PFCs) disrupt cholesterol homeostasis. All steroid hormones are derived from cholesterol, and steroid hormones such as glucocorticoids and androgenic hormones mediate several vital physiologic functions. However, the in utero effects of PFCs exposure on the homeostasis of these steroid hormones are not well understood in humans. We examined the relationship between prenatal exposure to perfluorooctane sulfonate (PFOS)/perfluorooctanoate (PFOA) and cord blood levels of glucocorticoid and androgenic hormones. We conducted a hospital-based birth cohort study between July 2002 and October 2005 in Sapporo, Japan (n = 514). In total, 185 mother-infant pairs were included in the present study. Prenatal PFOS and PFOA levels in maternal serum samples were measured using liquid chromatography-tandem mass spectrometry (LC-MS-MS). Cord blood levels of glucocorticoid (cortisol and cortisone) and androgenic hormones [dehydroepiandrosterone (DHEA) and androstenedione] were also measured in the same way. We found a dose-response relationship of prenatal PFOS, but not PFOA, exposure with glucocorticoid levels after adjusting for potential confounders. Cortisol and cortisone concentrations were -23.98-ng/mL (95% CI: -0.47.12, -11.99; p for trend = 0.006) and -63.21-ng/mL (95% CI: -132.56, -26.72; p for trend blood. Citation: Goudarzi H, Araki A, Itoh S, Sasaki S, Miyashita C, Mitsui T, Nakazawa H, Nonomura K, Kishi R. 2017. The association of prenatal exposure to perfluorinated chemicals with glucocorticoid and androgenic hormones in cord blood samples: the Hokkaido Study. Environ Health Perspect 125:111-118; http://dx.doi.org/10.1289/EHP142.

Prednisolone and prednisone neo-formation in bovine urine after sampling.

Science.gov (United States)

Arioli, F; Casati, A; Fidani, M; Silvestri, M; Pompa, G

2012-06-01

The rise in the frequency of detecting prednisolone in bovine urine from northern Italy has come into focus of attention in recent years. The possibility that neo-formation of prednisolone or that prednisone may occur in urine after collection of samples was therefore investigated. Cow urine collected for official routine controls in Lombardy containing more than 80 ng/ml cortisol, and prednisolone and prednisone below the decision limit (CCα) of the method (0.4 and 0.5 ng/ml, respectively) was used. The C1-2 dehydrogenation of naturally present cortisol and cortisone was checked by incubating urine, both contaminated and uncontaminated with faeces, at 37°C and by collecting samples at 0, 1, 2, 4, 6 and 24 h. The influence of Helix pomatia juice was also investigated in order to determine whether deconjugation could influence the reliability of the results. All samples were analysed by HPLC-MS3 for the presence of cortisol, cortisone, prednisolone and prednisone in negative electrospray ionisation mode, utilising the consecutive reaction monitoring of product ions derived from the formate molecular adduct ([M+HCOO]-). The observed neo-formation of prednisolone shows that inappropriate temperatures in sample storage and processing can result in an incorrect accusation of non-compliance. The faecal contamination of urine, performed with the aim to mimic a collection conducted without the necessary care, moreover, evoked a high increase in prednisolone concentration in two out of seven animals. Moreover, H. pomatia juice had no significant effect on the prednisolone concentration, indicating that this corticosteroid is present in its free form in cow urine.

Microstructure of microemulsion modified with ionic liquids in microemulsion electrokinetic chromatography and analysis of seven corticosteroids.

Science.gov (United States)

Ni, Xinjiong; Yu, Meijuan; Cao, Yuhua; Cao, Guangqun

2013-09-01

In this work, the influences of ionic liquid (IL) as a modifier on microemulsion microstructure and separation performance in MEEKC were investigated. Experimental results showed that synergetic effect between IL 1-butyl-3-methylimidazolium tetrafluoro-borate (BmimBF4 ) and surfactant SDS gave a decreased CMC. With increment of IL in microemulsion, negative ζ potential of the microdroplets reduced gradually. The influence of IL on the dimensions of microdroplet was complicated. At BmimBF4 less than 8 mM, IL made microemulsion droplet smaller in size. While at BmimBF4 more than 10 mM, the size increased and reached to a maximum value at 12 mM, where the microdroplets were larger than that without IL. After that, the micreodroplet size decreased again. Relative fluorescence intensity of the first vibration band of pyrene to the third one (I1 /I3 ) enhanced as IL was added to microemulsion, which indicated that this addition increased environmental polarity in the inner core of microdroplets. Prednisone, hydrocortisone, prednisolone, hydrocortisone acetate, cortisone acetate, prednisolone acetate, and triamcinolone acetonide were analyzed with MEEKC modified with IL to evaluate the separation performance. Cortisone acetate and prednisolone acetate could not be separated at all in typical microemulsion. The seven analytes could be separated by the addition of 10 mM BmimBF4 into the microemulsion system. The method has been used for analysis of corticosteroids in cosmetic samples with simple extraction; the recoveries for seven analytes were between 86 and 114%. This method provides accuracy, reproducibility, pretreatment simplicity, and could be applied to the quality control of cosmetics. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Diagnosis and Management of Combined Central Diabetes Insipidus and Cerebral Salt Wasting Syndrome After Traumatic Brain Injury.

Science.gov (United States)

Wu, Xuehai; Zhou, Xiaolan; Gao, Liang; Wu, Xing; Fei, Li; Mao, Ying; Hu, Jin; Zhou, Liangfu

2016-04-01

Combined central diabetes insipidus and cerebral salt wasting syndrome after traumatic brain injury (TBI) is rare, is characterized by massive polyuria leading to severe water and electrolyte disturbances, and usually is associated with very high mortality mainly as a result of delayed diagnosis and improper management. We retrospectively reviewed the clinical presentation, management, and outcomes of 11 patients who developed combined central diabetes insipidus and cerebral salt wasting syndrome after traumatic brain injury to define distinctive features for timely diagnosis and proper management. The most typical clinical presentation was massive polyuria (10,000 mL/24 hours or >1000 mL/hour) refractory to vasopressin alone but responsive to vasopressin plus cortisone acetate. Other characteristic presentations included low central venous pressure, high brain natriuretic peptide precursor level without cardiac dysfunction, high 24-hour urine sodium excretion and hypovolemia, and much higher urine than serum osmolarity; normal serum sodium level and urine specific gravity can also be present. Timely and adequate infusion of sodium chloride was key in treatment. Of 11 patients, 5 had a good prognosis 3 months later (Extended Glasgow Outcome Scale score ≥6), 1 had an Extended Glasgow Outcome Scale score of 4, 2 died in the hospital of brain hernia, and 3 developed a vegetative state. For combined diabetes insipidus and cerebral salt wasting syndrome after traumatic brain injury, massive polyuria is a major typical presentation, and intensive monitoring of fluid and sodium status is key for timely diagnosis. To achieve a favorable outcome, proper sodium chloride supplementation and cortisone acetate and vasopressin coadministration are key. Copyright © 2016 Elsevier Inc. All rights reserved.

Development and validation of a GC-C-IRMS method for the confirmation analysis of pseudo-endogenous glucocorticoids in doping control.

Science.gov (United States)

de la Torre, Xavier; Curcio, Davide; Colamonici, Cristiana; Molaioni, Francesco; Cilia, Marta; Botrè, Francesco

2015-01-01

Glucocorticoids are included in the S9 section of the World Anti-doping Agency (WADA) prohibited list international standard. Some among them are pseudo-endogenous steroids, like cortisol and cortisone, which present the same chemical structure as endogenously produced steroids. We are proposing an analytical method based on gas chromatography coupled to isotope ratio mass spectrometry (GC-C-IRMS) which allows discrimination between endogenous and synthetic origin of the urinary metabolites of the pseudo-endogenous glucocorticoids. A preliminary purification treatment by high-performance liquid chromatography (HPLC) of the target compounds (TC) (i.e., cortisol, tetrahydrocortisone (THE) 5α-tetrahydrocortisone (aTHE), tetrahydrocortisol (THF), and 5α-tetrahydrocortisol (aTHF)) allows collection of extracts with adequate purity for the subsequent analysis by IRMS. A population of 40 urine samples was analyzed for the TC and for the endogenous reference compounds (ERC: i.e., 11-desoxy-tetrahydrocortisol (THS) or pregnanediol). For each sample, the difference between the delta values of the ERCs and TCs (Δδ values) were calculated and based on that, some decision limits for atypical findings are proposed. The limits are below 3% units except for cortisol. The fit to purpose of the method has been confirmed by the analysis of urine samples collected in two patients under treatment with 25 mg of cortisone acetate (p.o). The samples showed Δδ values higher than 3 for at least 24 h following administration depending on the TC considered. The method can easily be integrated into existing procedures already used for the HPLC purification and IRMS analysis of pseudo-endogenous steroids with androgenic/anabolic activity. Copyright © 2015 John Wiley & Sons, Ltd.

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.

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.

Expression of 11beta-hydroxysteroid dehydrogenase 1 and 2 in subcutaneous adipose tissue of lean and obese women with and without polycystic ovary syndrome

DEFF Research Database (Denmark)

Svendsen, P F; Madsbad, S; Nilas, L

2009-01-01

OBJECTIVE: To investigate the expression of 11beta-hydroxysteroid dehydrogenase (11beta-HSD) type 1 and 2 and hexose-6-phosphate dehydrogenase (H6PDH) mRNA in subcutaneous abdominal tissue from lean and obese women with and without polycystic ovary syndrome (PCOS), and to investigate...... assessment insulin resistance index. Body composition was evaluated by dual X-ray absorptiometry. Adipose mRNA expression of leptin and adiponectin were determined by real-time PCR. RESULTS: Polycystic ovary syndrome (P... distribution (PPolycystic ovary syndrome and obesity are independently associated with increased expression of 11beta-HSD1. This may lead to increased conversion of cortisone to cortisol...

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

International Nuclear Information System (INIS)

Stahl, C.; Kang, C.H.; Phlvers, E.; Haasters, J.; Thuemler, P.

1985-01-01

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. (author)

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.

On the value of radioimmunologic myoglobin determination in skeletal muscle disorders

International Nuclear Information System (INIS)

Kiessling, W.R.; Beckmann, R.

1981-01-01

Using a sensitive radioimmunoassay (RIA) serum myoglobin (Mb) was measured in healthy controls, patients with skeletal muscle disorders (polymyositis, different types of progressive muscular dystrophy, hypokalemic myopathy and myopathy due to cortisone treatment) and as well in definite as possible carriers of Duchenne muscular dystrophy, DMD. The results indicate that Mb is a useful parameter in the assessment of muscle cell damage. Moreover, definite DMD-carriers had hypermyoglobine in 70% and in two of twenty possible DMD-carriers (all had normal CK activities) Mb was found to be markedly increased. The usefulness of an additional Mb determination in the detection of DMD-carriers is discussed. (orig.) [de

Value of radioimmunologic myoglobin determination in skeletal muscle disorders

Energy Technology Data Exchange (ETDEWEB)

Kiessling, W.R.; Beckmann, R.

1981-12-01

Using a sensitive radioimmunoassay (RIA) serum myoglobin (Mb) was measured in healthy controls, patients with skeletal muscle disorders (polymyositis, different types of progressive muscular dystrophy, hypokalemic myopathy and myopathy due to cortisone treatment) and as well in definite as possible carriers of Duchenne muscular dystrophy, DMD. The results indicate that Mb is a useful parameter in the assessment of muscle cell damage. Moreover, definite DMD-carriers had hypermyoglobine in 70% and in two of twenty possible DMD-carriers (all had normal CK activities) Mb was found to be markedly increased. The usefulness of an additional Mb determination in the detection of DMD-carriers is discussed.

Long term cortison treatment inhibits pubertal development in male common carp, Cyprinus carpio L.

NARCIS (Netherlands)

Consten, D.; Bogerd, J.; Komen, J.; Lambert, J.G.D.; Goos, H.J.Th.

2001-01-01

The onset and regulation of puberty is determined by functional development of the brain-pituitary-gonad (BPG) axis. Stress has been shown to interfere with reproduction and the functioning of the BPG axis. The response to chronic and severe stress may require much energy and force the organism to

Intraarticular cortisone injection for osteoarthritis of the hip. Is it effective? Is it safe?

Science.gov (United States)

Kruse, David W

2008-12-01

Osteoarthritis of the hip is a significant source of morbidity in the elderly. Treatment guidelines are available for the management of hip osteoarthritis, but these do not address the application of intraarticular corticosteroid injection. The intraarticular injection of corticosteroid is used in the management of other large joint osteoarthritic diseases and is well studied in the knee, however, this data cannot be used to make sound clinical decisions regarding its use for hip osteoarthritis. There are also concerns regarding the safety of this modality. Review of the published literature reveals that there are eight trials examining the efficacy of intraarticular corticosteroid injection for hip osteoarthritis and of these only four are randomized controlled trials. In general, the available literature demonstrates a short-term reduction of pain with corticosteroid injection and is indicated for patients refractory to non-pharmacologic or analgesic and NSAID therapy. The use of radiologic-guidance is recommended and, with proper sterile technique, the risk of adverse outcomes is very low. Future randomized controlled trials are needed to further examine the efficacy and safety of intraarticular corticosteroid injection for hip osteoarthritis.

Intraarticular cortisone injection for osteoarthritis of the hip. Is it effective? Is it safe?

OpenAIRE

Kruse, David W.

2008-01-01

Osteoarthritis of the hip is a significant source of morbidity in the elderly. Treatment guidelines are available for the management of hip osteoarthritis, but these do not address the application of intraarticular corticosteroid injection. The intraarticular injection of corticosteroid is used in the management of other large joint osteoarthritic diseases and is well studied in the knee, however, this data cannot be used to make sound clinical decisions regarding its use for hip osteoarthrit...

Fabric phase sorptive extraction-high performance liquid chromatography-photo diode array detection method for simultaneous monitoring of three inflammatory bowel disease treatment drugs in whole blood, plasma and urine.

Science.gov (United States)

Kabir, Abuzar; Furton, Kenneth G; Tinari, Nicola; Grossi, Laurino; Innosa, Denise; Macerola, Daniela; Tartaglia, Angela; Di Donato, Valentina; D'Ovidio, Cristian; Locatelli, Marcello

2018-05-01

This paper reports a novel fabric phase sorptive extraction-high performance liquid chromatography-photodiode array detection (FPSE-HPLC-PDA) method for the simultaneous extraction and analysis of three drug residues (ciprofloxacin, sulfasalazine, and cortisone) in human whole blood, plasma, and urine samples, generally administered in human patients to treat inflammatory bowel disease (IBD). The drugs of interest were well resolved using a Luna C 18 column (250 mm × 4.6 mm; 5 μm particle size) in gradient elution mode within 20 min. The analytical method was optimized and validated in the range 0.05-10 μg/mL for whole blood, 0.25-10 μg/mL for human plasma, and 0.10-10 μg/mL for human urine. Blank human whole blood, plasma, and urine were used as the sample matrix for the method development and validation; while methyl-p-hydroxybenzoate was used as the internal standard (IS). Weighted-matrix matched standard calibration curves showed a good linearity up to a concentration of 10 μg/mL. The intra- and inter-day accuracy values (precision and trueness) were found in the range from -10.9% to 12.3%, and the performances of the validated FPSE-HPLC-PDA were further tested on real IBD patient samples. This is the first FPSE procedure applied simultaneously to whole blood, plasma, and urine samples for the determination of residual IBD drugs, which possess a wide range of polarity (logP values ranging from 2.30 for Ciprofloxacin, to 1.66 for Cortisone, and 2.92 for Sulfasalazine). The new approach exhibits high potential for immediate adoptation as a rapid, robust and green analytical tool for future clinical and pharmaceutical applications. Copyright © 2018 Elsevier B.V. All rights reserved.

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

Increased whole-body and sustained liver cortisol regeneration by 11beta-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

2011-03-01

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. Ten obese men with type 2 diabetes and seven normal-weight control subjects were infused with 9,11,12,12-[(2)H](4)cortisol (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. In obese type 2 diabetic subjects, the appearance rate of 9,12,12-[(2)H](3)cortisol 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. 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.

Lead transfer in maternal milk, and the absorption, retention, distribution and excretion of lead in suckling mice

Energy Technology Data Exchange (ETDEWEB)

Keller, Charles Arthur [Univ. of Rochester, NY (United States). Dept. of Radiation Biology and Biophysics

1980-01-01

Suckling mice were found to absorb and retain a greater fraction of an oral lead dose than did adult mice. Pinocytotic activity and lead uptake (in vivo) were found to be greatest in the distal small intestinal tissue. Cortisone pretreatment results in precocious cessation of pinocytotic activity in the intestine of suckling mice. Cortisone pretreatment of adult mice had no effect on whole body lead retention or intestinal tissue content of lead following an oral dose. The data indicate that the distal small intestine is the site of active pinocytosis of lead, and that pinocytosis is the major mechanism involved in lead absorption in suckling mice. Developmental differences were also observed in the percentage of lead retained in the whole body. Both groups exhibited dose-independent lead retention, indicating a first-order absorption process for each age group. Lead distribution and elimination from organs also differed between suckling and adult mice. Developmental differences were observed in organ lead concentration for kidneys and brain following oral doses. Relative distribution of lead to the brains of suckling mice were greater than to adult brains. Whole body and bone lead elimination rates were reduced in suckling compared to adult mice. Brain lead elimination rates did not differ in suckling and adult mice. A lactating mouse model was developed to study lead transfer to suckling offspring. Lead was transferred in milk to suckling offspring from mothers which had previously ingested lead in the drinking water. Relative lead transfer to suckled offspring during lactation greatly exceeded transfer to fetuses during gestation. Lactation resulted in an increased rate of maternal lead elimination. Lead concentration in milk exceeded plasma concentration by a factor of approximately 25. (ERB)

Radioimmunoassay of aldosterone in adrenal venous effluent in a case of Conn's syndrome, ch. 5a

International Nuclear Information System (INIS)

Froelich, M.; Bruning, P.F.; Moolenaar, A.J.

1977-01-01

In a case of Conn's syndrome samples were obtained from the venous effluent of both adrenals and from peripheral veins during venography. The aldosterone concentration was measured by means of radioimmunoassay. The sensitivty of the aldosterone assay was 27 pg (P<0.05), the parallelism between the standard and the serum dilutions was excellent and there was no cross-reaction with cortisol, cortisone, 21-desoxycortisol, dexamethasone or spironolactone in amounts up to 1 μg per incubation. The aldosterone concentrations measured in peripheral venous blood were 220-250 ng/100 ml serum. In the effluent of the left adrenal, in which an aldosterone producing tumor was localized, an aldosterone level of 8480 ng/100 ml serum was estimated

Psychosomatic disturbances at patients with uterine corpus cancer with cortisolemia of various expression at stages of the combined treatment

International Nuclear Information System (INIS)

Prokhach, N.E.; Sorochan, P.P.; Gromakova, Yi.A.; Kuz'menko, O.V.; Yivanenko, M.O.

2015-01-01

The assessment of an integrated indicator of quality of life, indicators of emotional and cognitive functioning, indicators of fatigue, pain and sleep disorders at stages of the combined treatment at patients with uterine corpus cancer with cortisolemia of various expression is carried out. Psychosomatic disorders are least expressed at patients with the low and high level of a hydrocortisone whereas patients with intermediate levels of a hydro-cortisone have more expressed fatigue, the feeling of pain, essential sleep disorders is stronger. Clarification of the mechanisms involved to development of psychosomatic disturbances in patients with different expression of a cortisolemia is necessary for development of the individualized strategy of prophylaxis and treatment focused on conservation of quality of life

Femoral nerve compression syndrome with paresis of the quadriceps muscle caused by radiotherapy of malignant tumours. A report of four cases

Energy Technology Data Exchange (ETDEWEB)

Laurent, L E [Orthopaedic Hospital of the Invalid Foundation, Helsinki, Finland

1975-01-01

Four patients showed signs of femoral nerve compression with subsequent paresis of the quadriceps muscle, after radiation therapy of malignant tumours. The compression was caused by scar tissue due to radiation treatment of the inguinal region. The first symptom was radiating pain in the front of the thigh and lower leg which appeared 12-16 months after X-ray treatment. A decrease in the strength of quadriceps muscle occurred some months later. In one case the femoral nerve was decompressed, another patient was treated by an intradural phenolglycerin injection and one patient was treated with cortisone and oxiphenbutanzone. In these cases the pain decreased considerably, but in one case only the paresis of the quadriceps muscle improved after treatment.

Attenuation of the cortisol response to stress in female rainbow trout chronically exposed to dietary selenomethionine

International Nuclear Information System (INIS)

Wiseman, Steve; Thomas, Jith K.; McPhee, Landon; Hursky, Olesya; Raine, Jason C.; Pietrock, Michael; Giesy, John P.; Hecker, Markus; Janz, David M.

2011-01-01

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

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

Disability and pain after cortisone versus placebo injection for trapeziometacarpal arthrosis and de Quervain syndrome

NARCIS (Netherlands)

Makarawung, Dennis J. S.; Becker, Stéphanie J. E.; Bekkers, Stijn; Ring, David

2013-01-01

This study tested the null hypothesis that type of injection (corticosteroid vs. placebo) is not a predictor of arm-specific disability as measured with the Disabilities of Arm, Shoulder and Hand questionnaire 1 to 3 months after injection of dexamethasone or placebo for treatment of

Clinical and experimental keratitis caused by the Colletotrichum state of Glomerella cingulata and Acrophialophora fusispora.

Science.gov (United States)

Shukla, P K; Khan, Z A; Lal, B; Agrawal, P K; Srivastava, O P

1983-06-01

Two cases of mycotic keratitis caused by the Colletotrichum state of Glomerella cingulata and Acrophialophora fusispora are reported for the first time. Both the isolates produced experimental corneal lesions in rabbit eyes but A. fusispora was more pathogenic. The experimental infection was more severe, with both the fungi, in rabbits pretreated with cortisone as compared with untreated animals. In vitro A. fusispora was most sensitive to miconazole and tolciclate followed by clotrimazole, amphotericin B and lactones while clotrimazole exerted maximum inhibitory effect on Colletotrichum followed by miconazole, lactones, amphotericin B and arnebins. Arnebins and tolciclate were inactive respectively against A. fusispora and Colletotrichum. Of the 3 drugs tested in vivo, against A. fusispora keratitis in rabbit, amphotericin B showed better results than tolciclate and miconazole.

The RIA studies on the changes of serum hormone levels during induction stage of intravenous anesthesia with three different drugs

International Nuclear Information System (INIS)

Lan Changsheng; Huang Jianmin; Pan Liping; Li Dongxue; Feng Rongfang

2002-01-01

Objective: To investigate of effects of propofol, thiopental and etomidate on pituitary adrenal functions during the induction stage of intravenous anaesthesia with them. Methods: Forty-eight patients undergoing elective surgery were randomly divided into three groups, propofol (group I), thipental (group II) and etomidate (group III). Peripheral blood samples were taken for the measurement of E, NE, PRL, GH, B-EP and cortisone before induction (T 0 ), During induction (T 1 ) and 2, 5, 15 min after intubation with RIA. Results: The study showed that none of the three drugs could inhibit increase in E and NE during induction and intubation, but propofol was significantly better than the other two. Conclusion: Propofol has less effects on pituitary-adrenal functions and is the drug of choice for induction

Aseptic necrosis of the femoral head following treatment of malignant lymphomas

Energy Technology Data Exchange (ETDEWEB)

Kuhn, E; Kovacs, A

1986-01-01

Three cases with avascular necrosis of the femoral head are reported of which one showed bilateral disease. Two patients with Hodgkin's disease of mixed cellularity underwent polychemotherapy; the third with gastric centroblastic non-Hodgkin lymphoma received abdominal irradiation followed by 3 courses of polychemotherapy. Total dose of prednisolone administered varied between 4,080-7,045 mg. Time elapsed between appearance of pain and significant radiologic features was several months. Patients with Hodgkin's disease were young and were both exposed to significant physical strain. Multiple factors are thought to be responsible for this late sequel of therapy in which the role of cortisone is stressed. Computed tomography is of great value in detecting disease at an early phase and depicting its real extent.

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

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

A switch in hepatic cortisol metabolism across the spectrum of non alcoholic fatty liver disease.

Directory of Open Access Journals (Sweden)

Adeeba Ahmed

Full Text Available 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.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.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.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 11β-HSD1 activity and consequent cortisol regeneration may

A switch in hepatic cortisol metabolism across the spectrum of non alcoholic fatty liver disease.

Science.gov (United States)

Ahmed, Adeeba; Rabbitt, Elizabeth; Brady, Theresa; Brown, Claire; Guest, Peter; Bujalska, Iwona J; Doig, Craig; Newsome, Philip N; Hubscher, Stefan; Elias, Elwyn; Adams, David H; Tomlinson, Jeremy W; Stewart, Paul M

2012-01-01

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). 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. 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. 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 11β-HSD1 activity and consequent cortisol regeneration may serve to

Masked volume wise principal component analysis of small adrenocortical tumours in dynamic [11C]-metomidate positron emission tomography

International Nuclear Information System (INIS)

Razifar, Pasha; Hennings, Joakim; Monazzam, Azita; Hellman, Per; Långström, Bengt; Sundin, Anders

2009-01-01

In previous clinical Positron Emission Tomography (PET) studies novel approaches for application of Principal Component Analysis (PCA) on dynamic PET images such as Masked Volume Wise PCA (MVW-PCA) have been introduced. MVW-PCA was shown to be a feasible multivariate analysis technique, which, without modeling assumptions, could extract and separate organs and tissues with different kinetic behaviors into different principal components (MVW-PCs) and improve the image quality. In this study, MVW-PCA was applied to 14 dynamic 11C-metomidate-PET (MTO-PET) examinations of 7 patients with small adrenocortical tumours. MTO-PET was performed before and 3 days after starting per oral cortisone treatment. The whole dataset, reconstructed by filtered back projection (FBP) 0–45 minutes after the tracer injection, was used to study the tracer pharmacokinetics. Early, intermediate and late pharmacokinetic phases could be isolated in this manner. The MVW-PC1 images correlated well to the conventionally summed image data (15–45 minutes) but the image noise in the former was considerably lower. PET measurements performed by defining 'hot spot' regions of interest (ROIs) comprising 4 contiguous pixels with the highest radioactivity concentration showed a trend towards higher SUVs when the ROIs were outlined in the MVW-PC1 component than in the summed images. Time activity curves derived from '50% cut-off' ROIs based on an isocontour function whereby the pixels with SUVs between 50 to 100% of the highest radioactivity concentration were delineated, showed a significant decrease of the SUVs in normal adrenal glands and in adrenocortical adenomas after cortisone treatment. In addition to the clear decrease in image noise and the improved contrast between different structures with MVW-PCA, the results indicate that the definition of ROIs may be more accurate and precise in MVW-PC1 images than in conventional summed images. This might improve the precision of PET

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.

Symposium: evidence for the use of intra-articular cortisone or hyaluronic acid injection in the hip

Science.gov (United States)

Chandrasekaran, Sivashankar; Lodhia, Parth; Suarez-Ahedo, Carlos; Vemula, S. Pavan; Martin, Timothy J.; Domb, Benjamin G.

2016-01-01

The primary purpose of this review article is to discuss the role of diagnostic, corticosteroid, hyaluronic acid (HA) and platelet rich plasma (PRP) in the treatment of osteoarthritis (OA) and femoroacetabular impingement (FIA). These treatments play an important biological role in the non-operative management of these conditions. Two independent reviewers performed an search of PubMed for articles that contained at least one of the following search terms pertaining to intra-articular hip injection—local anaesthetic, diagnostic, ultrasound, fluoroscopic, image guided, corticosteroid, HA, PRP, OA, labral tears and FAI. Seventy-two full text articles were suitable for inclusion. There were 18 articles addressing the efficacy of diagnostic intra-articular hip injections. With respect to efficacy in OA there were 25 articles pertaining to efficacy of corticosteroid, 22 of HA and 4 of PRP. There were three articles addressing the efficacy of biologics in FAI. Diagnostic intra-articular hip injections are sensitive and specific for differentiating between intra-articular, extra-articular and spinal causes of hip symptoms. Ultrasound and fluoroscopy improves the precision of intra-articular positioning of diagnostic injections. Corticosteroids are more effective than HA and PRP in alleviating pain from hip OA. A higher dose of corticosteroids produces a longer benefit but volume of injection has no significant effect. Intra-articular corticosteroids do not increase infection rates of subsequent arthroplasty. There is currently limited evidence to warrant the routine use of therapeutic injections in the management of labral tears and FIA. PMID:27026814

Sodium alginate-grafted β-cyclodextrins as a matrix for immobilized Arthrobacter simplex for cortisone acetate biotransfromation

Science.gov (United States)

Shen, Yanbing; Niu, Lulu; Yu, Ziqi; Wang, Min; Shang, Zhihua; Yang, Yan

2018-06-01

Cyclodextrins (CDs) are used to resolve the low aqueous solubility of steroids, but the high cost of CDs is still a limiting factor in biotransformation process. This study, which is based on grafting and immobilization techniques, focused on synthesizing for the first time sodium alginate (SA)-grafted β-CD (SA-β-CD) and alginate-grafted β-CD for the immobilization of Arthrobacter simplex (ASP) cells (SA-β-CD-cells) and subsequent recycling of CDs and cells. FTIR spectium and X-ray diffraction proved that β-CD was successfully grafted with SA, whereas the grafting yield of β-CD was 10.3 μmol g-1. SA-β-CD could increase the solubility of CA by 3.5-fold, whereas the transformation rate was enhanced by 10%. The conversion ratio of CA was over 92% after the SA-β-CD recycling for nine cycles. In addition, after SA-β-CD-cells were applied in biocatalytic reactions for eight cycles, the conversion ratio of CA was over 90%. These advantages suggest great potential for using both grafting and immobilized techniques in steroid transformation.

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

2018-01-01

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.

[Contact allergy to henna tattoos].

Science.gov (United States)

Steinkjer, Bjarte; Stangeland, Katarina Zak; Mikkelsen, Carsten Sauer

2011-03-18

Tattoos with henna colours have become very popular and the prevalence of contact allergy seems to increase. This is a short review article based on our own clinical experience and literature identified through a search in PubMed with the words "henna", "paraphenylendiamin" and "allergic contact dermatitis." A case report is included. It is well documented that many experience skin reactions after henna tattoos. The cause is almost always contact allergy to the azo compound paraphenylendiamin, which is added to speed up the process and make the colour darker. Most people, including children, get henna tattoos during vacations in Asia or the Mediterranean. Established contact allergy is permanent. Many hair-colour products contain paraphenylendiamin, and persons with contact allergy against the product may develop a very strong contact allergic eczema by use of such substances. Acute reactions are treated with local cortisone products, or with systemic steroids. Cross reaction to substances with a similar chemical structure may occur. Tattoos with paraphenylendiamin-containing henna colours should be avoided.

Therapeutic application of 99Tc-MDP in advanced nodose rheumatoid patients with multiple arthrosis erosion and malfunctioning

International Nuclear Information System (INIS)

Yuan Jiming

2001-01-01

Objective: To evaluate clinical effect of 99 Tc-MDP in treating arthrosis erosion in advanced nodose rheumatism. Methods: Therapy was performed undisrupted for 1 to 2 years in each patient at a high dose of 1.0-1.5 g/month. Results: After more than 1 year's 99 Tc-MDP therapy, 10 patients with multiple arthrosis erosion and serious malfunctioning had function recovery and arthral reformation of different extent. Patients with obvious therapeutic effects were able to walk, travel and completely or partially took care of themselves. Cortisone was prohibited or permitted at a lower dose of 1.25 mg/day in 3 patients who were dependant on prednisone. As results from 99 Tc-MDP therapy, X-ray photography revealed broadened arthral gap, reformation of previously eroded arthrosis and even improvement in osteoporosis. Conclusion: Reversible changes resulted from 99 Tc-MDP therapy showed breakthrough in treatment of advanced nodose rheumatism and serious ostearthritis, whose pathological changes were previously considered irreversible

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.

Vascularized osseous graft for scaphoid

International Nuclear Information System (INIS)

Mendez Daza, Carlos Hernan; Mathoulin, Cristophe

2004-01-01

The most commonly used technique for treatment of pseudo-arthrosis of the scaphoid is osteo-synthesis with Kirschnet wires and cortical sponge grafts. Results reported by different teams using this procedure show no more than 90% osseous consolidation, especially in cases where vascularisation of the proximal fragment of the scaphoid is compromised. Here we present a series of ten cases of pseudo-arthrosis of the scaphoid, treated using a new surgical technique involving a vascularized osseous graft of the distal radius. Using this procedure we obtained 100% consolidation, with no complications either during the procedure or immediately post-operatively. Patients returned to work in week 15 on average. In 4 cases we observed discomfort in the area of the scar, which was successfully treated using local cortisone injection. The results obtained are very similar to those seen in the literature on the different techniques for vascularized osseous grafts for pseudo-arthrosis of the scaphoid

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. Copyright © 2017. Published by Elsevier B.V.

A new technique for promoting cyclic utilization of cyclodextrins in biotransformation.

Science.gov (United States)

Shen, Yanbing; Yu, Ziqi; Yang, Xu; Wang, Fang; Luo, Jianmei; Wang, Min

2017-01-01

Cyclodextrins (CDs) can improve the productivity of steroid biotransformation by enhancing substrate solubility. CDs can be recycled by grafting them with appropriate carriers. Loofah fiber is an excellent grafting material for CDs, and can be applied to the biotransformation and recycling of β-cyclodextrin (β-CD). In this work, a technique for recycling β-CD in cortisone acetate (CA) biotransformation by Arthrobacter simplex CPCC 140451 was studied. Loofah fiber-grafted β-CD (LF-β-CD) was prepared using epichlorohydrin, which is a cross-linking agent. The grafting yield of β-CD was 74.8 mg g -1 dried fibers. LF-β-CD could increase the solubility of CA and enhance biotransformation. The initial conversion rate of CA was 1.5-fold higher than that of the blank group. LF-β-CD was also used in biocatalytic reactions for eight cycles, and it maintained the conversion ratio of CA at approximately 90%. Given the above positive results, LF-β-CD can be utilized in biotechnological recycling applications. This method can also be applied to CD derivatives and hydrophobic compounds.

[Rheologic studies in chronic agressive hepatitis].

Science.gov (United States)

Leonhardt, H; Bungert, H J

1975-10-01

The chronic aggressive hepatitis, type II b, is attended by an elevation of the plasma and blood viscosity values, which corresponds to the degree of the mesenchymal and parenchymatous inflammation. This elevation is mainly due to a pathological increase of those immunglobuline fractions which are effective on the viscosity. During the application of a fluocortolon monotherapy, there could be noticed a regression as well as a normalisation of the primarily pathological laboratory parameters, being typical for an aggressive hepatitis. These changes were correlated to a decrease of the blood and plasma viscosity. The improved blood flow property is considered to be caused by the decrease of the IgG-fraction. The significance of an improved blood flow property will be discussed in correlation to the effect of the microcirculation, resulting in a better nutrition of the cell with the necessary nutritive substances, as well as on the regression of the inflammatory parameters hereby provoked. In addition to the possible benefits of the introduced cortison therapy will be considered in this context.

Bee sting therapy-induced hepatotoxicity: A case report.

Science.gov (United States)

Alqutub, Adel Nazmi; Masoodi, Ibrahim; Alsayari, Khalid; Alomair, Ahmed

2011-10-27

The use of bee venom as a therapeutic agent for the relief of joint pains dates back to Hippocrates, and references to the treatment can be found in ancient Egyptian and Greek medical writings as well. Also known as apitherapy, the technique is widely used in Eastern Europe, Asia, and South America. The beneficial effects of bee stings can be attributed to mellitinin, an anti-inflammatory agent, known to be hundred times stronger than cortisone. Unfortunately, certain substances in the bee venom trigger allergic reactions which can be life threatening in a sensitized individual. Multiple stings are known to cause hemolysis, kidney injury, hepatotoxicity and myocardial infarction. The toxicity can be immediate or can manifest itself only weeks after the exposure. We describe hepatotoxicity in a 35-year-old female, following bee sting therapy for multiple sclerosis. She presented to our clinic 3 wk after therapy with a history of progressive jaundice. The patient subsequently improved, and has been attending our clinic now for the last 9 mo.

Adrenal disorders and non-alcoholic fatty liver disease.

Science.gov (United States)

Papanastasiou, Labrini; Fountoulakis, Stelios; Vatalas, Ioannis-Anastasios

2017-06-01

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the developed world and its pathogenesis is complex and multifactorial. It is considered the hepatic manifestation of the metabolic syndrome and is the leading cause of hepatic cirrhosis. This review aims to present current knowledge on the involvement of the adrenal glands in the development of NAFLD. Clinical and animal studies have shown that excess glucocorticoids (GC) have been implicated in the pathogenesis of NAFLD. Patients with NAFLD seem to have a subtle chronic activation of the hypothalamic pituitary adrenal axis leading to a state of subclinical hypercortisolism. Regulators of GC such as 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), an enzyme that regenerates cortisol from inactive cortisone, and 5α/5β-reductases, enzymes that increase cortisol clearance, are implicated in the development of NAFLD by amplifying local GC action. Adrenal androgen (dehydroepiandrosterone) abnormalities and increased aldosterone levels may also have a role in the development of NAFLD whereas the contribution of adrenergic signaling in NAFLD pathogenesis remains unclear.

Increased cortisol bioavailability, abdominal obesity, and the metabolic syndrome in obese women.

Science.gov (United States)

Duclos, Martine; Marquez Pereira, Patricia; Barat, Pascal; Gatta, Blandin; Roger, Patrick

2005-07-01

This study was conducted to obtain a detailed profile of hypothalamo-pituitary-adrenal (HPA) axis activity and reactivity and its differential relationships with body fat distribution and total fat mass in premenopausal obese women. Cortisol responses to stimulation (awakening, food intake, exercise) and suppression (0.25 mg dexamethasone), cortisol metabolism, and tissue sensitivity to glucocorticoids were studied in 53 premenopausal obese women grouped according to their waist-to hip ratio: women with abdominal body fat distribution (A-BFD; n = 31) and women with peripheral fat distribution (P-BFD; n = 22). Comparatively, A-BFD women had 1) lower awakening salivary cortisol levels; 2) increased salivary responsiveness to a standardized lunch; 3) similar pituitary sensitivity to dexamethasone but decreased sensitivity of monocytes to dexamethasone; 4) similar 24-hour urinary free cortisol but increased 24-hour urinary ratio of cortisone-to-cortisol; and 5) no difference in corticosteroid binding protein parameters. Although abdominal obesity is not very different from generalized obesity in terms of HPA function, subtle variations in HPA axis activity and reactivity are evidenced in A-BFD premenopausal obese women.

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.

[Hormones and hair growth].

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Trüeb, R M

2010-06-01

With respect to the relationship between hormones and hair growth, the role of androgens for androgenetic alopecia (AGA) and hirsutism is best acknowledged. Accordingly, therapeutic strategies that intervene in androgen metabolism have been successfully developed for treatment of these conditions. Clinical observations of hair conditions involving hormones beyond the androgen horizon have determined their role in regulation of hair growth: estrogens, prolactin, thyroid hormone, cortisone, growth hormone (GH), and melatonin. Primary GH resistance is characterized by thin hair, while acromegaly may cause hypertrichosis. Hyperprolactinemia may cause hair loss and hirsutism. Partial synchronization of the hair cycle in anagen during late pregnancy points to an estrogen effect, while aromatase inhibitors cause hair loss. Hair loss in a causal relationship to thyroid disorders is well documented. In contrast to AGA, senescent alopecia affects the hair in a diffuse manner. The question arises, whether the hypothesis that a causal relationship exists between the age-related reduction of circulating hormones and organ function also applies to hair and the aging of hair.

Stress, memory, and the hippocampus.

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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. © 2014 S. Karger AG, Basel

Two Qatari siblings with cystic fibrosis and apparent mineralocorticoid excess

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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.

Metabolism of progesterone-4-14C in organ cultures of fetal adrenal glands in the human being

International Nuclear Information System (INIS)

Weber, S.

1979-01-01

1. In 72 hours of incubation in two subsequent cultures, progesterone-4- 14 C was converted into different corticosteroids and androgenes by using explants of the adrenal glands in organ cultures, which were taken from a male fetus with a crown-to-rump length of 8.5 cm. In the most cases the water-dilutable metabolites are steroidsulfates. 2. The following individual progesterone metabolites were found: 17α-hydroxyprogesterone-4- 14 C, 16α-hydroxyprogesterone-4- 14 C, corticosterone-4- 14 C, cortisole-4- 14 C, cortisone-4- 14 C, androstendione-4- 14 C, and 11β-hydroxyandrostendione-4- 14 C. 3. These steroides let appear possible the presence and efficacy of the following enzyme systems: 17α-hydroxylase, 16α-hydroxylase, 21-hydroxylase, 11β-hydroxylase, 11β-hydroxysteroide-dehydrogenase, and Csub(17-20) desmolase. 4. Calculations of our dates by the analogue computer, which are present by now, apparently seem to render possible the kinetic of the corticosteroide biosynthesis in the tissue of fetal adrenal glands by organ cultures, because under the present conditions incubations can be carried out for considerably longer periods than by cell fractions, cell homogenates, and organ sections. (orig.) [de

Combination of Estrogen and Immunosuppressive Agents to Establish a Mouse Model of Candidiasis with Concurrent Oral and Vaginal Mucosal Infection.

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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.

Identification of UGT2B9*2 and UGT2B33 isolated from female rhesus monkey liver.

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Dean, Brian; Arison, Byron; Chang, Steve; Thomas, Paul E; King, Christopher

2004-06-01

Two UDP-glucuronosyltransferases (UGT2B9(*)2 and UGT2B33) have been isolated from female rhesus monkey liver. Microsomal preparations of the cell lines expressing the UGTs catalyzed the glucuronidation of the general substrate 7-hydroxy-4-(trifluoromethyl)coumarin in addition to selected estrogens (beta-estradiol and estriol) and opioids (morphine, naloxone, and naltrexone). UGT2B9(*)2 displayed highest efficiency for beta-estradiol-17-glucuronide production and did not catalyze the glucuronidation of naltrexone. UGT2B33 displayed highest efficiency for estriol and did not catalyze the glucuronidation of beta-estradiol. UGT2B9(*)2 was found also to catalyze the glucuronidation of 4-hydroxyestrone, 16-epiestriol, and hyodeoxycholic acid, while UGT2B33 was capable of conjugating 4-hydroxyestrone, androsterone, diclofenac, and hyodeoxycholic acid. Three glucocorticoids (cortisone, cortisol, and corticosterone) were not substrates for glucuronidation by liver or kidney microsomes or any expressed UGTs. Our current data suggest the use of beta-estradiol-3-glucuronidation, beta-estradiol-17-glucuronidation, and estriol-17-glucuronidation to assay UGT1A01, UGT2B9(*)2, and UGT2B33 activity in rhesus liver microsomes, respectively.

Virtual reality jogging as a novel exposure paradigm for the acute urge to be physically active in patients with eating disorders: Implications for treatment.

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Paslakis, Georgios; Fauck, Vanessa; Röder, Kathrin; Rauh, Elisabeth; Rauh, Manfred; Erim, Yesim

2017-11-01

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 3D 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.

Mechanized sephadex LH-20 multiple column chromatography as a prerequisite to automated multi-steroid radioimmunoassays

International Nuclear Information System (INIS)

Sippell, W.G.; Bidlingmaier, F.; Knorr, D.

1977-01-01

In order to establish a procedure for the simultaneous determination of all major corticosteroid hormones and their immediate biological precursors in the same plasma sample, two different mechanized methods for the simultaneous isolation of aldosterone (A), corticosterone (B), 11-deoxycorticosterone (DOC), progesterone (P), 17-hydroxyprogesterone (17-OHP), 11-deoxycorticol (S), cortisol (F), and cortisone (E) from the methylene chloride extracts of 0.1 to 2.0 ml plasma samples have been developed. In both methods, eluate fractions of each of the isolated steroids are automatically pooled and collected from all parallel columns by one programmable linear fraction collector. Due to the high reproducibility of the elution patterns both between different parallel columns and between 30 to 40 consecutive elutions, mean recoveries of tritiated steroids including extraction are 60 to 84% after a single elution and still over 50% after an additional chromatography on 40cm LH-20 colums, with coefficients of variation below 15%. Thus, the eight steroids can be completely isolated from each of ten plasma extracts within 3 to 4 hours, yielding 80 samples readily prepared for subsequent quantitation by radioimmunoassay. (orig./AJ) [de

[Correlations between the hypothalamo-pituitary-adrenal axis and the metabolic syndrome].

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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.

Endocrine regulation of carbohydrate metabolism in hypometabolic animals

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Musacchia, X. J.

1988-01-01

Experimental hypothermia and natural hibernation are two forms of hypometabolism with recognized physiological changes, including depression of endocrine and metabolic functions. To better understand functional changes, helox (i.e., helium and oxygen (80:20) mixtures) and low ambient temperatures have been used to induce hypothermia in hamsters and rats. Both clinical and biological survival, i.e., survival without recovery and survival with recovery from hypothermia, respectively, are related to depth and length of hypothermia. In the rat, body temperatures of 15 degrees C for periods greater than 6-10 h greatly restrict biological survival. The role of glucocorticoids in enhancing thermogenic capacity of rats was assessed using triamcinolone [correction of triamcinalone] acetonide. In the hamster, treatment with cortisone acetate prolonged both clinical and biological survival. Hypothermic hamsters continue utilizing circulating glucose until they become hypoglycemic and die. Hypothermic rats do not utilize glucose and respond with a significant hypoinsulinema. The role of endocrines in the regulation of carbohydrate homeostasis and metabolism differs in hibernation and hypothermia. Glucocorticoids influence the hypothermic response in both species, specifically by prolonging induction of hypothermia in rats and by prolonging survival in hypothermic hamsters.

Separation of corticosteroids by microemulsion EKC with diethyl L-tartrate as the oil phase.

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Wu, Chi-Hung; Chen, Tse-Hsien; Huang, Kuan-Pin; Wang, Guan-Ren; Liu, Chuen-Ying

2007-10-01

A novel microemulsion based on a mixture of diethyl L-tartrate (DET) and SDS was developed for the microemulsion EKC (MEEKC) determination of structurally related steroids. The system consisted of 0.5% w/w DET, 1.7% w/w SDS, 1.2% w/w 1-butanol, 89.6% w/w phosphate buffer (40 mM, pH 7.0), and 7% w/w ACN. With an applied voltage of +10 kV, a baseline separation of aldosterone (A), cortisone acetate (CA), dexamethasone (D), hydrocortisone (H), hydrocortisone acetate (HA), prednisolone (P), prednisolone acetate (PA), prednisone (Ps), triamcinolone (T), and triamcinolone acetonide (TA) could be achieved. Under the optimized conditions, the reproducibility of the retention time (n = 4) for most of the compounds was less than +/-0.8% with the exception of A, Ps, and T. The average number of theoretical plates was 18 800 plates/m. The results were compared with those achieved by the modified micellar EKC (MEKC). MEEKC showed obvious advantages over MEKC for the separation of highly hydrophobic substances. To further evaluate the system, we tested the MEEKC method by analyzing corticosteroids in a spiked urine sample.

Investigations of the microbial transformation of cortisol to prednisolone in urine samples.

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Bredehöft, Michael; Baginski, Rainer; Parr, Maria-Kristina; Thevis, Mario; Schänzer, Wilhelm

2012-03-01

Doping control samples are normally collected under non-sterile conditions and sometimes, storage and transportation are influenced by parameters such as the temperature. Therefore, microbial contamination and subsequent alteration of a sample's composition are possible. Studies regarding sample collection in cattle breeding have already shown enzymatic transformation of endogenous testosterone to boldenone causing false-positive findings. The aim of the present study was to investigate whether positive doping cases with the synthetic corticosteroids prednisolone and prednisone may result from microbial transformation of the endogenous corticosteroids cortisol and cortisone, respectively. A method comprising parameters such as pH values and screening results for synthetic glucocorticosteroids as well as incubation experiments followed by liquid chromatographic and mass spectrometric analysis was employed to test for contaminating germs with Δ(1)-dehydrogenase activity. Over 700 urine samples comprising inpatient and doping control specimens were investigated. In none of them, 1,2-dehydrogenating activity was confirmed. These findings are in accordance with other studies. However, the problem of microbial alteration of doping control specimens with special respect to 1,2-dehydrogenation must not be underestimated. Article from a special issue on steroids and microorganisms. Copyright © 2010 Elsevier Ltd. All rights reserved.

Development of an assay for urinary free cortisol determination on the Technicon Immuno 1 system

International Nuclear Information System (INIS)

Letellier, M.; Levesque, A.; Daigle, F.

1997-01-01

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)

Radioligand binding assay of cortisol using horse transcortin

International Nuclear Information System (INIS)

Dash, R.J.; Sharma, B.R.; Lata, V.

1979-01-01

A modified radioligand binding assay was developed to measure cortisol in a single methylene chloride extract of human plasma/serum. The assay utilises 5 percent horse serum for cortisol binding and 3 H-cortisol as tracer. Except for a cross reaction of 13.3 percent for cortisone and 7 percent for prednisolone that for other steroids tested was negligible. The assay sensitivity at the lower 95 percent inhibition of buffer controls was 20 pg/tube. The log dose logit response standard curve was linear between 80 pg and 5 ng/tube. Recovery(Y) of cortisol added (x) to male and pregnant female plasma was quantitated (y = 0.983 X-0.47, r = 0.98). Regression analysis of cortisol estimates obtained in 51 plasma/serum samples with this assay system and a specific radioimmunoassay (using cortisol-3-BSA antiserum) for plasma cortisol gave a coefficient of correlation (r) of 0.95 and a regression coefficient (b) of 0.97. The method was found to be simple and highly reproducible. Availability of all reagents in the aqueous phase permitted handling of a large number of samples by a single technician. (auth.)

A multi-modal treatment approach for the shoulder: A 4 patient case series

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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.

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.

Hormones in infant rhesus monkeys' (Macaca mulatta) hair at birth provide a window into the fetal environment.

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Kapoor, Amita; Lubach, Gabriele; Hedman, Curtis; Ziegler, Toni E; Coe, Christopher L

2014-04-01

It is established that maternal parity can affect infant growth and risk for several disorders, but the prenatal endocrine milieu that contributes to these outcomes is still largely unknown. Recently, it has been shown that hormones deposited in hair can provide a retrospective reflection of hormone levels while the hair was growing. Taking advantage of this finding, our study utilized hair at birth to investigate if maternal parity affected fetal hormone exposure during late gestation. Hair was collected from primiparous and multiparous mother and infant monkeys at birth and used to determine steroid hormones embedded in hair while the infant was in utero. A high-pressure liquid chromatography-triple quadrupole mass spectrometry technique was refined, which enabled the simultaneous measurement of eight hormones. Hormone concentrations were dramatically higher in neonatal compared to maternal hair, reflecting extended fetal exposure as the first hair was growing. Further, hair cortisone was higher in primiparous mothers and infants when compared to the multiparous dyads. This research demonstrates that infant hair can be used to track fetal hormone exposure and a panel of steroid hormones can be quantified from hair specimens. Given the utility in nonhuman primates, this approach can be translated to a clinical setting with human infants.

Aplastic anemia as a feature of systemic lupus erythematosus: a case report and literature review.

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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.

Patterns of endogenous steroids in apathetic refugee children are compatible with long-term stress

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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.

Determination of endogenous and exogenous corticosteroids in bovine urine and effect of fighting stress during the "Batailles des Reines" on their biosynthesis.

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Leporati, Marta; Nobile, Maria; Capra, Pierluigi; Alladio, Eugenio; Vincenti, Marco

2017-10-01

Natural corticosteroids include two families of substances: mineralocorticoids and glucocorticoids. Several drugs of similar structure and biological activity have been synthesized and are currently used in the clinical practice. Beside legal pharmacological treatments, these drugs have been consistently misused in animal breeding. One of the most abused corticosteroids is prednisolone. For many years, prednisolone has been considered of exclusive synthetic origin, but nowadays a debate about its possible endogenous production is under way. Several studies have been addressed to ascertain the potential relationship between stressful conditions, such as transportation and slaughtering, and endogenous production of prednisolone. In order to verify further the effect of stressful conditions, our laboratory analysed urine samples collected from the cows participating to the "Batailles des Reines" (a traditional contest based on ritual and spontaneous fights of pregnant cows), to verify if an endogenous prednisolone production may occur in these animals. We developed and validated a LC-MS/MS method for the simultaneous determination of cortisol, cortisone, prednisolone and five of its metabolites. The method was applied to the analysis of urine samples collected from "Batailles des Reines" competitions in 2012 and 2013. All these samples had been previously analysed within an anti-doping control program and tested compliant to all screenings. Copyright © 2017 Elsevier Ltd. All rights reserved.

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.

In vitro and in vivo antimicrobial activities of seeds of Caesalpinia bonduc (Lin.) Roxb.

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Arif, Tasleem; Mandal, T K; Kumar, Naresh; Bhosale, J D; Hole, Archana; Sharma, G L; Padhi, M M; Lavekar, G S; Dabur, Rajesh

2009-05-04

Caesalpinia bonduc (Lin.) Roxb. is a known drug in Ayurveda to treat various diseases specifically tumors, cysts and cystic fibrosis (CF). The aim of this study was to assess in vitro as well as in vivo antimicrobial activity of Caesalpinia bonduc seeds. The in vitro antimicrobial activities of seed coat and seed kernel extracts were investigated by microbroth dilution assay. In vivo activities of hydro-alcoholic extracts were investigated in rat models of chronic Pseudomonas aeruginosa pneumonia mimicking that in patients with cystic fibrosis. Various extracts of plant seeds exhibited in vitro antimicrobial activities in a range of 22-350 microg/ml. The extracts also showed activity against methicillin resistant (MR) Staphylococcus aureus and ampicillin resistant (AR) Pseudomonas aeruginosa as in the sensitive strains. In rat model of chronic Pseudomonas aeruginosa pneumonia, hydro-alcoholic extracts of Caesalpinia bonduc seed kernel (CBSK) and Caesalpinia bonduc seed coat (CBSC) were injected subcutaneously in the test groups of animals. The control groups were treated with cortisone and saline. Two weeks after challenge with Pseudomonas aeruginosa, the CBSK treated animals showed a significant bacterial clearance from the lungs (PCaesalpinia bonduc may have the potential to be promising natural medicine, with other forms of treatments, for CF patients with chronic Pseudomonas aeruginosa lung infections.

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.

Cortisol intermediates and hydrocortisone responsiveness in critical neonatal disease.

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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.

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.

[Botulism. Therapeutic management. Apropos of 36 cases].

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Sudre, Y; Becq-Giraudon, B; Boutaud, P h

1975-03-08

Botulism is relatively common in the Vienne department as we have observed 36 cases over a peroid of 7 years. Other French cases, published over the last 10 years, included 10 to 19 cases in the largest series. In a total of 10 series, there were 105 cases. Botulism is caused, in most cases, by eating ham prepared on the farm. It gives rise to the usual clinical picture including paralysis of accommodation, dysphagia, digestive symptoms with abdominal pain and constipation and finally, bladder paralysis. The mild forms are fairly common. We did not observe any severe cases. Our patients were treated in two homogeneous series of 17 cases each ; two patients were given no treatment. Patients treated by sero-anatoxin therapy according to classical methods, evolved towards a cure within 21 days on average. Patients treated by sulfguanidin were cured within 24 days. This study permitted us to confirm that sero-anatoxin therapy is not essential. The disadvantages are the number of injections, the possibility of sometimes fatal hyper-sensitive reactions which, in the opinion of many authors, justifies routine cover with cortisone. This attitude does not seem to us justified owing to the usually benign nature of the botulism. The treatment with sulfaguanidin is well tolerated and is not of any risk to the patient.

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.

Experimental Modification of Rat Pituitary Growth Hormone Cell Function During and After Spaceflight

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Hymer, W. C.; Salada, T.; Nye, P.; Grossman, E. J.; Lane, P. K.; Grindeland, R. E.

1996-01-01

Space-flown rats show a number of flight-induced changes in the structure and function of pituitary Growth Hormone (GH) cells after in vitro postflight testing. To evaluate the possible effects of microgravity on GH cells themselves, freshly dispersed rat anterior pituitary gland cells were seeded into vials containing serum +/- 1 micron HydroCortisone (HC) before flight. Five different cell preparations were used: the entire mixed-cell population of various hormone-producing cell types, cells of density less than 1.071 g/sq cm (band 1), cells of density greater than 1.071 g/sq cm (band 2), and cells prepared from either the dorsal or ventral part of the gland. Relative to ground control samples, bioactive GH released from dense cells during flight was reduced in HC-free medium but was increased in HC-containing medium. Band I and mixed cells usually showed opposite HC-dependent responses. Release of bioactive GH from ventral flight cells was lower; postflight responses to GH-releasing hormone challenge were reduced, and the cytoplasmic area occupied by GH in the dense cells was greater. Collectively, the data show that the chemistry and cellular makeup of the culture system modifies the response of GH cells to microgravity. As such, these cells offer a system to identify gravisensing mechanisms in secretory cells in future microgravity research.

[Weight-loss drugs: composition of diet pills prescribed in Navarra].

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Oria, E; Jáuregui, A; Iriarte, A; Olondriz, J; Anderiz, B; Pérez de Ciriza, J A; Lafita, J; Cameo, M V; Roldán, E

1997-06-01

The prescription, dispensation and sale of "Magisterial formulas" for weight loss is a very extended practice in Spain, in spite of being strongly unadvised by different Administration Department as well as by medical and sanitary groups. The composition of these preparations is not labelled if so only in a generic way. The content of 54 capsules from 6 different origins (3 medical consultations, 1 pharmacist consultation, 1 free sale in pharmacies and 1 free sale in stores) was analysed in 2 laboratories. The presence and quantity of 29 active principles was searched by spectrophotometry, chromatography and radioimmunoassay. The presence of some of the 12 following substances was confirmed in 42 samples (77.8%): hormones (levothyroxine, cortisol and cortisone), appetite suppression phenetilamines (amphetamine, amphepranone, fenfluramine and fenproporex), benzodiazepines (diazepam, clorazepato and chlordiazepoxide) and diuretics (triamterene and ciclotiazide). The quantities of active principles was very variable in and among the six groups. In 13 of the capsules 1 active principle and in 29 combinations of two or more was found. None component of the labels, when available, corresponded with their analysed components. In 12 samples (22.2%) none of the which may correspond to some substances different from the 29 sought ones. The usage of formulas as the studied here on the overweight and obesity treatment should be obviously unadvised.

Distribution of an 125I-labelled chloroquine analogue in a pregnant macaca monkey

International Nuclear Information System (INIS)

Dencker, L.; Lindquist, N.G.; Ullberg, S.

1975-01-01

Whole body autoradiography of a pregnant monkey (Macaca irus) of late gestation was performed 72 h after an intravenous injection of the 125 I-labelled chloroquine analogue 4-(3-dimethylaminopropylamino)-7-iodoquinoline (DAPQ). The overall distribution pattern in the monkey was similar to that which was earlier observed in rodents. A few species differences, however, were found in the monkey as compared to the rodents: a high accumulation in the inner part of the adrenal cortex, a high level in the central nervous system, and generally a higher retention in the tissues. The accumulation in the cortex may be of significance for the cortisone-like effects of the 4-aminoquinolines in rheumatoid arthritis and allied conditions. The fact that no accumulation was found in the adrenal cortex of mice and rats indicates that these species may not be appropriate in studies on the mechanisms involved in the anti-inflammatory action of the 4-aminoquinolines. As was earlier observed in small rodents the melanin containing structures accumulated the drug. In both the mother and the fetus a high concentration was thus seen in the uveal tract of the eye, in the inner ear (in the stria vascularis of the cochlea and the planum semilunatum of the ampullae) and in the hair follicles. This accumulation can be related to reported disturbances-also transplacentally induced-in vision and hearing

Abnormal expression of 11 beta-hydroxysteroid dehydrogenase type 2 in human pituitary adenomas: a prereceptor determinant of pituitary cell proliferation.

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Rabbitt, E H; Ayuk, J; Boelaert, K; Sheppard, M C; Hewison, M; Stewart, P M; Gittoes, N J L

2003-03-20

The physiological effects of glucocorticoids (GCs) are, at least in part, mediated by inhibition of cell proliferation. Two isozymes of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) interconvert cortisol (F) and inactive cortisone (E), and are thus able to modulate GC action at an autocrine level. Previously, we have demonstrated absent expression of 11 beta-HSD2 in normal pituitaries; however, in a small number of pituitary tumors analysed, 11 beta-HSD2 was readily demonstrable. Here we have used real-time RT-PCR to quantify expression of mRNA for 11 beta-HSD1 and 2 in 105 human pituitary tumors and have performed enzyme expression and activity studies in primary pituitary cultures. Overall, pituitary tumors expressed lower levels of 11 beta-HSDl mRNA compared with normals (0.2-fold, Pprotein (mean+/-s.d.)) but no detectable 11 beta-HSDl activity. Proliferation assays showed that addition of glycyrrhetinic acid (an 11 beta-HSD2 inhibitor) resulted in a 30.3+/-7.7% inhibition of cell proliferation. In summary, we describe a switch in expression from 11 beta-HSDl to 11 beta-HSD2 in neoplastic pituitary tissue. We propose that abnormal expression of 11 beta-HSD2 acts as a proproliferative prereceptor determinant of pituitary cell growth, and may provide a novel target for future tumor therapy.

The morphology of ovine Trypanosoma melophagium (zoomastigophorea: kinetoplastida).

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Büscher, G; Friedhoff, K T

1984-02-01

Morphologic and biometric data on bloodstream stages of Trypanosoma melophagium are presented. An increasing parasitemia with 111 trypomastigote stages of T. melophagium were found in Giemsa-stained thin blood smears taken from a splenectomized, cortisone-treated sheep recently infested with Melophagus ovinus infected with T. melophagium . The arithmetic mean and standard deviation in micron of the distances between posterior end and kinetoplast were 14.7 and 2.9, from the kinetoplastic to the center of the nucleus 5.1 and 1.1, and from there to the anterior end 19.5 and 1.9. The free flagellum measured 6.0 microns +/- 1.6 microns. The median and the range of the central 70% of values (median +/- 35%) of the nuclear index were 1.1 and 0.9-1.2 and of the kinetoplastic index 3.8 and 3.3-4.9. The same data in microns for the maximal width were 3.1 and 2.1-4.6, and for the width at the level of the nucleus 2.9 and 2.2-4.6. The larger and smaller diameters of the nucleus measured 2.6 (2.2-3.7) micron and 1.7 (1.3-1.7) micron, respectively. The corresponding kinetoplast diameters were 1.1 (0.9-1.3) microns and 0.9 (0.6-0.9) micron, respectively.

Premature adrenarche: novel lessons from early onset androgen excess.

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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.

Wars in the history of rheumatology

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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.

Altered cortisol metabolism in polycystic ovary syndrome: insulin enhances 5alpha-reduction but not the elevated adrenal steroid production rates.

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Tsilchorozidou, Tasoula; Honour, John W; Conway, Gerard S

2003-12-01

Androgen excess in women with polycystic ovary syndrome (PCOS) may be ovarian and/or adrenal in origin, and one proposed contributing mechanism is altered cortisol metabolism. Increased peripheral metabolism of cortisol may occur by enhanced inactivation of cortisol by 5alpha-reductase (5alpha-R) or impaired reactivation of cortisol from cortisone by 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) resulting in decreased negative feedback suppression of ACTH secretion maintaining normal plasma cortisol concentrations at the expense of androgen excess. We have tested whether any enzyme dysregulation was related to circulating insulin or androgen concentrations in women with PCOS and have sought to clarify their relationship with obesity. First, to avoid obesity-related effects on cortisol metabolism, 18 lean women with PCOS were compared with 19 lean controls who were closely matched for body mass index (BMI). Second, the impact of obesity was studied in a cross-section of 42 PCOS women of a broad range of BMI. We measured 24-h urinary excretion of steroid metabolites by gas chromatography/mass spectrometry and fasting metabolic and hormone profiles. Urinary excretion of androgens [androsterone (P = 0.003), etiocholanolone (P = 0.02), and C19 steroid sulfates (P = 0.009)], cortisone metabolites [tetrahydrocortisone (THE) (P = 0.02), alpha-cortolone (P lean PCOS subjects when compared with controls. A significantly higher 5alpha-tetrahydrocortisol (5alpha-THF)/5beta-THF ratio (P = 0.04) and a significantly lower alpha-THF + THF + alpha-cortol/THE + cortolones ratio (P = 0.01) were found in lean PCOS women compared with lean controls, indicating both enhanced 5alpha-R and reduced 11beta-HSD1 activities. A decreased THE/cortolones ratio (P = 0.03) was also found in lean PCOS women compared with lean controls, indicating increased 20 alpha/beta-HSD activity. In the group of 42 PCOS subjects, measures of 5alpha/5beta reduction were positively correlated with the

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.

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 < 0·01). Forty-eight per cent of patients showed abnormal fatigue, while 61% had severe fatigue. The CIS fatigue scores were significantly higher compared to controls (P < 0·01). We found reduced general subjective health-related QoL scores in both male and female patients, especially in younger patients <65 years of age. Physical activity is decreased in patients with Addison's disease, combined with a reduced subjective health-related QoL and increased fatigue. © 2016 John Wiley & Sons Ltd.

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.

Proliferation and Differentiation of Autologic and Allogenic Stem Cells in Supralethally X-Irradiated Dogs

Energy Technology Data Exchange (ETDEWEB)

Chertkov, I. L. [Department of Radiobiology, Central Institute of Haematology and Blood Transfusion, Moscow, USSR (Russian Federation)

1967-07-15

Full text: Allogenic bone marrow after transplantation into dogs irradiated with 1000 R X-rays differentiates in the normal way only for 3-4 days, afterwards transforming into lymphoid cells. This transformation is due to the antigen stimulus of the host on the grafted stem cells. The lymphoid cells, obtained from the host's blood on the 7-8th day after grafting, showed specific, immune activity under the Immune Lymphocyte Transfer test. Within a short duration of the immune response immunoblasts and immunocytes Undergo degenerative changes: destroyed mitochondria, formation of autophagic vacuoles and, finally, lysis of the cells. These changes are suggested to be the result of overloading of immune cells with antigen. Preliminary sensitization of the donor with prospective host's haemopoietic tissue does not hasten the immune transformation of haemopoiesis. Injections of bacterial pyrogen, cortisone or 6-mercaptopurine into recipients, as well as incubation of bone marrow at 37 Degree-Sign C for 2 hours, do not prevent the immune transformation. Preliminary thymectomy of the prospective recipients prevents in some of the cases immune transformation of the bone-marrow graft. The delay of allogenic bone-marrow transplantation for 5-6 days prevents in some dogs (X-irradiated with 1000 R, but not with 1200 R) the immune transformation. Transplantation of autologic bone marrow or shielding of the legs during irradiation is accompanied with good restoration of normal haemopoiesis without lymphoid transformation. (author)

Differential protective effects of immune lymphoid cells against transplanted line Ib leukemia and immune polioencephalomyelitis

International Nuclear Information System (INIS)

Duffey, P.S.; Lukasewycz, O.A.; Olson, D.S.; Murphy, W.H.

1978-01-01

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 10 PD 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

The role of 11?-hydroxysteroid dehydrogenase type 1 and type2 isoenzymes on the pathogenesis of Cushing’s syndrome - doi:10.5020/18061230.2007.p104

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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.

Tracheomalacia associated with Mounier-Kuhn syndrome in the Intensive Care Unit: treatment with Freitag stent. A case report.

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Giannoni, S; Benassai, C; Allori, O; Valeri, E; Ferri, L; Dragotto, A

2004-09-01

Tracheomalacia is a process characterized by softness of the supporting tracheal cartilages, by the extension of the posterior membranous wall and by reduction of the tracheal antero-posterior diameter. Exceptionally, tracheomalacia can be associated with tracheobronchomegaly or Mounier-Kuhn syndrome. Fibro-bronchoscopy represents the ''gold standard'' for diagnosis. The case of a 79-year-old male observed after hospitalization in a medical ward for chronic pulmonary obstructive disease (COPD) decompensation, and with basal left bronchopulmonary focus, is described. During this period, a progressive worsening of clinical conditions occurred, despite cortisone and antibiotic therapy, and the patient was transferred to the ICU for dyspnea, hypoxia, hypocapnia and with a diagnosis of pulmonary fibrosis. Bronchoscopy, performed during spontaneous breathing, revealed tracheomalacia which was responsible for tracheal dynamic complete stenosis during expiration and dynamic subtotal stenosis of the left primary bronchus in the first tract, together with sputum retention. Moreover, this investigation confirmed the diagnosis of tracheobronchomegaly already seen on CT. It was suggested to place a Freitag stent, since the insertion of another model would not have had enough chance of stability, due to the enormous extension of the tracheal lumen and could not have guaranteed good clearance of the secretions. Seven days after this intervention, performed in an outpatients' setting, the patient was dismissed from the ICU, without the help of O2, with good ventilation, saturation in line with his age and good expectoration.

Quantification of steroid hormones in human serum by liquid chromatography-high resolution tandem mass spectrometry.

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Matysik, Silke; Liebisch, Gerhard

2017-12-01

A limited specificity is inherent to immunoassays for steroid hormone analysis. To improve selectivity mass spectrometric analysis of steroid hormones by liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been introduced in the clinical laboratory over the past years usually with low mass resolution triple-quadrupole instruments or more recently by high resolution mass spectrometry (HR-MS). Here we introduce liquid chromatography-high resolution tandem mass spectrometry (LC-MS/HR-MS) to further increase selectivity of steroid hormone quantification. Application of HR-MS demonstrates an enhanced selectivity compared to low mass resolution. Separation of isobaric interferences reduces background noise and avoids overestimation. Samples were prepared by automated liquid-liquid extraction with MTBE. The LC-MS/HR-MS method using a quadrupole-Orbitrap analyzer includes eight steroid hormones i.e. androstenedione, corticosterone, cortisol, cortisone, 11-deoxycortisol, 17-hydroxyprogesterone, progesterone, and testosterone. It has a run-time of 5.3min and was validated according to the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) guidelines. For most of the analytes coefficient of variation were 10% or lower and LOQs were determined significantly below 1ng/ml. Full product ion spectra including accurate masses substantiate compound identification by matching their masses and ratios with authentic standards. In summary, quantification of steroid hormones by LC-MS/HR-MS is applicable for clinical diagnostics and holds also promise for highly selective quantification of other small molecules. Copyright © 2017 Elsevier B.V. All rights reserved.

Apparent mineralocorticoid excess and the long term treatment of genetic hypertension.

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Razzaghy-Azar, Maryam; Yau, Mabel; Khattab, Ahmed; New, Maria I

2017-01-01

Apparent mineralocorticoid excess (AME) is a genetic disorder causing severe hypertension, hypokalemia, and hyporeninemic hypoaldosteronism owing to deficient 11 beta-hydroxysteroid dehydrogenase type-2 (11βHSD2) enzyme activity. The 11βHSD2 enzyme confers mineralocorticoid receptor specificity for aldosterone by converting cortisol to its inactive metabolite, cortisone and inactivating the cortisol-mineralocorticoid receptor complex. The 20year follow-up of a consanguineous Iranian family with three sibs affected with AME shows the successes and pitfalls of medical therapy with spironolactone. The three sibs, (female, male, female) were diagnosed at the ages of 14, 11, and 4 years, respectively. At diagnosis, hypertensive retinopathy and left ventricular hypertrophy were present in the eldest female and retinopathy was noted in the male sib. Spironolactone treatment resulted in decreased blood pressure and rise in serum potassium levels. The older female, age 36, developed reduced left ventricular function with mitral and tricuspid regurgitation and renal failure after her second pregnancy. She was treated with renal transplantation resulting in cure of AME with decreased blood pressure and weaning from antihypertensives. Her younger sibs, age 34 and 26, do not have end organ damage. Early and vigilant treatment improves morbidity in patients with AME. Mineralocorticoid receptor antagonists normalize blood pressure, correct hypokalemia and reduce hypertensive end-organ damage in patients with AME. Low dose dexamethasone can be considered, though the response may be variable. Future directions of therapy include selective mineralocorticoid antagonists. Copyright © 2016 Elsevier Ltd. All rights reserved.

Immunotherapy of murine leukemia. Efficacy of passive serum therapy of Friend leukemia virus-induced disease in immunocompromised mice

International Nuclear Information System (INIS)

Genovesi, E.V.; Livnat, D.; Collins, J.J.

1983-01-01

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 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

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.

Efficacy of SCH27899 in an Animal Model of Legionnaires' Disease Using Immunocompromised A/J Mice

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Brieland, Joan K.; Loebenberg, David; Menzel, Fred; Hare, Roberta S.

2000-01-01

The efficacy of SCH27899, a new everninomicin antibiotic, against replicative Legionella pneumophila lung infections in an immunocompromised host was evaluated using a murine model of Legionnaires' disease. A/J mice were immunocompromised with cortisone acetate and inoculated intratracheally with L. pneumophila serogroup 1 (105 CFU per mouse). At 24 h postinoculation, mice were administered either SCH27899 (6 to 60 mg/kg [MPK] intravenously) or a placebo once daily for 5 days, and mortality and intrapulmonary growth of L. pneumophila were assessed. In the absence of SCH27899, there was 100% mortality in L. pneumophila-infected mice, with exponential intrapulmonary growth of the bacteria. In contrast, administration of SCH27899 at a dose of ≥30 MPK resulted in ≥90% survival of infected mice, which was associated with inhibition of intrapulmonary growth of L. pneumophila. In subsequent studies, the efficacy of SCH27899 was compared to ofloxacin (OFX) and azithromycin (AZI). Administration of SCH27899, OFX, or AZI at a dose of ≥30 MPK once daily for 5 days resulted in ≥85% survival of infected mice and inhibition of intrapulmonary growth of the bacteria. However, L. pneumophila CFU were recovered in lung homogenates following cessation of therapy with all three antibiotics. These studies demonstrate that SCH27899 effectively prevents fatal replicative L. pneumophila lung infection in immunocompromised A/J mice by inhibition of intrapulmonary growth of the bacteria. However, in this murine model of pulmonary legionellosis, SCH27899, like OFX and AZI, was bacteriostatic. PMID:10770771

Sclerodermie : Rapport de Quatre Cas

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P. Mohagheghi

1957-01-01

Full Text Available Four cases of sclerodermia have been reported durintwo months. Sclerodermia which seems to he hardness of the skin is actually a general affection that first appears on the skin and has various types: edematous, sclerema for children, and then the forms of patches or drops or bands Or annulars. It is sor t of connective tissue affection and is chiefly observed in women and as the reason for it, is thought to be due to the acute infections and chronic toxics in theory dysendocryno- sympathic that eventually is caused by nervous- mental disturbances and shocks."nThree of the pa t ients were adults and one of them was a 60 years old man. Clinical symptoms were common in all three persons and as a usual it began from the fingers and then it appeared in the face, but in the man it was different and the disease began first from the chest and abdomen and buttucks parts, and although the duration of the illness was more than few months it had not yet affected the limbs. After sometime it affects the muscles and bones and in a few years it expands so that causes a general weakness and eventually results in death."nThe treatment is tern porary and differs comparatively in different cases. Vitamin E given with large dosage, Vitamin D2 to keep calcium from running. Bismuth, Penicilline with large dosage and tetracycline given continuously, and at last cortisone and A.C. which have temporary and rapid results

Rapid determination of 18 glucocorticoids in serum using reusable on-line SPE polymeric monolithic column coupled with LC-quadrupole/orbitrap high-resolution mass spectrometer.

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Li, Hui; Ai, Lianfeng; Fan, Sufang; Wang, Yan; Sun, Dianxing

2017-10-15

A simple, rapid and sensitive method for the simultaneous determination of 18 glucocorticoids in serum was developed by coupling on-line solid-phase extraction (SPE) polymeric monolithic column to a liquid chromatography-quadrupole/orbitrap high-resolution mass spectrometer. A simple poly(ethylene glycol dimethacrylate) monolith column (10mm×2.1mm i.d.) was fabricated, and the morphology, surface area and extraction performance of the monolithic column were characterized. Serum samples were extracted by acetonitrile (ACN). Then, online SPE was achieved on the synthesized monolithic column using a 10mmol/L ammonium acetate solution as the loading solvent. After the transfer from the monolith into analytical column (Capcell Pak ADME column) using ACN, the adsorbed analytes were separated on the analytical column and detected with a high-resolution hybrid quadrupole/orbitrap mass spectrometer with full scan/ddMS 2 scan mode Under optimized conditions, the method was linear with target linear correlation coefficient (R 2 ) higher than 0.995. Detection limits were in range of 0.1-0.6ng/mL, and the quantification limits were 0.3-1.5ng/mL. The recovery was between 71.9% and 89.2% in three spike levels with precision (n=5) of 5.40-12.1%. The serum sample was directly analyzed after a simple extraction procedure, and the on-line SPE and determination were achieved within only 16min. The method was used to analyze the dynamic contents variation of cortisone and hydrocortisone in serum before and after the surgery. Copyright © 2017 Elsevier B.V. All rights reserved.

Discovery of safety biomarkers for atorvastatin in rat urine using mass spectrometry based metabolomics combined with global and targeted approach

International Nuclear Information System (INIS)

Kumar, Bhowmik Salil; Lee, Young-Joo; Yi, Hong Jae; Chung, Bong Chul; Jung, Byung Hwa

2010-01-01

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 -1 day -1 or 250 mg kg -1 day -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.

Discovery of safety biomarkers for atorvastatin in rat urine using mass spectrometry based metabolomics combined with global and targeted approach

Energy Technology Data Exchange (ETDEWEB)

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.

Plasma Nervonic Acid Is a Potential Biomarker for Major Depressive Disorder: A Pilot Study.

Science.gov (United States)

Kageyama, Yuki; Kasahara, Takaoki; Nakamura, Takemichi; Hattori, Kotaro; Deguchi, Yasuhiko; Tani, Munehide; Kuroda, Kenji; Yoshida, Sumiko; Goto, Yu-Ichi; Inoue, Koki; Kato, Tadafumi

2018-03-01

Diagnostic biomarkers of major depressive disorder, bipolar disorder, and schizophrenia are urgently needed, because none are currently available. We performed a comprehensive metabolome analysis of plasma samples from drug-free patients with major depressive disorder (n=9), bipolar disorder (n=6), schizophrenia (n=17), and matched healthy controls (n=19) (cohort 1) using liquid chromatography time-of-flight mass spectrometry. A significant effect of diagnosis was found for 2 metabolites: nervonic acid and cortisone, with nervonic acid being the most significantly altered. The reproducibility of the results and effects of psychotropic medication on nervonic acid were verified in cohort 2, an independent sample set of medicated patients [major depressive disorder (n=45), bipolar disorder (n=71), schizophrenia (n=115)], and controls (n=90) using gas chromatography time-of-flight mass spectrometry. The increased levels of nervonic acid in patients with major depressive disorder compared with controls and patients with bipolar disorder in cohort 1 were replicated in the independent sample set (cohort 2). In cohort 2, plasma nervonic acid levels were also increased in the patients with major depressive disorder compared with the patients with schizophrenia. In cohort 2, nervonic acid levels were increased in the depressive state in patients with major depressive disorder compared with the levels in the remission state in patients with major depressive disorder and the depressive state in patients with bipolar disorder. These results suggested that plasma nervonic acid is a good candidate biomarker for the depressive state of major depressive disorder. © The Author 2017. Published by Oxford University Press on behalf of CINP.

Mineralocorticoid hypertension and hypokalaemia induced by posaconazole.

Science.gov (United States)

Boughton, Charlotte; Taylor, David; Ghataore, Lea; Taylor, Norman; Whitelaw, Benjamin C

2018-01-01

We describe severe hypokalaemia and hypertension due to a mineralocorticoid effect in a patient with myelodysplastic syndrome taking posaconazole as antifungal prophylaxis. Two distinct mechanisms due to posaconazole are identified: inhibition of 11β hydroxylase leading to the accumulation of the mineralocorticoid hormone 11-deoxycorticosterone (DOC) and secondly, inhibition of 11β hydroxysteroid dehydrogenase type 2 (11βHSD2), as demonstrated by an elevated serum cortisol-to-cortisone ratio. The effects were ameliorated by spironolactone. We also suggest that posaconazole may cause cortisol insufficiency. Patients taking posaconazole should therefore be monitored for hypokalaemia, hypertension and symptoms of hypocortisolaemia, at the onset of treatment and on a monthly basis. Treatment with mineralocorticoid antagonists (spironolactone or eplerenone), supplementation of glucocorticoids (e.g. hydrocortisone) or dose reduction or cessation of posaconazole should all be considered as management strategies. Combined hypertension and hypokalaemia are suggestive of mineralocorticoid excess; further investigation is appropriate.If serum aldosterone is suppressed, then further investigation to assess for an alternative mineralocorticoid is appropriate, potentially using urine steroid profiling and/or serum steroid panelling.Posaconazole can cause both hypokalaemia and hypertension, and we propose that this is due to two mechanisms - both 11β hydroxylase inhibition and 11β HSD2 inhibition.Posaconazole treatment may lead to cortisol insufficiency, which may require treatment; however, in this clinical case, the effect was mild.First-line treatment of this presentation would likely be use of a mineralocorticoid antagonist.Patients taking posaconazole should be monitored for hypertension and hypokalaemia on initiation and monthly thereafter.

Selection of restriction specificities of virus-specific cytotoxic T cells in the thymus: no evidence for a crucial role of antigen-presenting cells

International Nuclear Information System (INIS)

Zinkernagel, R.M.

1982-01-01

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

The legacy of Hans Selye and the origins of stress research: a retrospective 75 years after his landmark brief "letter" to the editor# of nature.

Science.gov (United States)

Szabo, Sandor; Tache, Yvette; Somogyi, Arpad

2012-09-01

Hans Selye's single author short letter to Nature (1936, 138(3479):32) inspired a huge and still growing wave of medical research. His experiments with rats led to recognition of the "general adaptation syndrome", later renamed by Selye "stress response": the triad of enlarged adrenal glands, lymph node and thymic atrophy, and gastric erosions/ulcers. Because of the major role of glucocorticoids (named by Selye), he performed extensive structure-activity studies in the 1930s-1940s, resulting in the first rational classification of steroid hormones, e.g. corticoids, testoids/androgens, and folliculoids/estrogens. During those years, he recognized the respective anti- and pro-inflammatory actions of gluco- and mineralocorticoids in animal models, several years before demonstration of anti-rheumatic actions of cortisone and adrenocorticotrophic hormones in patients. Nevertheless, Selye did not receive a Nobel Prize, which was awarded in 1950 to the clinician Hench and the two chemists who isolated and synthesized some of the glucocorticoids. Nonetheless, Selye was internationally recognized as a world authority in endocrinology, steroid chemistry, experimental surgery, and pathology. He wrote over 1500 original and review articles, singly authored 32 books, and trained 40 PhD students, one of whom (Roger Guillemin) won a Nobel Prize for isolating the hypothalamic releasing factors/hormones. Here, we consider the main implications of his first article launching the biological stress concept and the key ideas and problems that occupied him. Selye considered "Stress in heath and disease is medically, sociologically, and philosophically the most meaningful subject for humanity that I can think of".

11beta-hydroxysteroid dehydrogenase complementary deoxyribonucleic acid in rainbow trout: cloning, sites of expression, and seasonal changes in gonads.

Science.gov (United States)

Kusakabe, Makoto; Nakamura, Ikumi; Young, Graham

2003-06-01

11beta-Hydroxysteroid dehydrogenases (11beta-HSDs) are important steroidogenic enzymes for catalyzing the interconversion of active glucocorticoid (cortisol and corticosterone) and inert 11-keto forms (cortisone and 11-dehydrocorticosterone) in mammals. In teleosts, 11beta-HSD also plays a role in the production of the predominant androgen, 11-ketotestosterone, in male fish. In this study we cloned cDNAs encoding rainbow trout 11beta-HSD (rt11beta-HSD) from testes and head kidney. The predicted amino acid sequence, hydrophobicity analysis, and transient transfection assays with rt11beta-HSD in HEK293 cells showed that rt11beta-HSD is a homolog of mammalian 11beta-HSD type 2. rt11beta-HSD transcripts are present in steroidogenic tissues and in a number of other tissues. Strong in situ hybridization signals for rt11beta-HSD transcripts were found in Leydig cells of testes, in thecal cells of the early vitellogenic ovarian follicles, and in thecal and granulosa cells of the midvitellogenic and postovulatory follicles. Weaker signals were also found in head kidney interrenal cells from juvenile rainbow trout. Seasonal changes in rt11beta-HSD transcripts in testes showed a pattern similar to that of stress-induced serum cortisol levels, but not to serum androgen levels. High levels of rt11beta-HSD transcripts were found in ovarian follicles from late vitellogenesis through ovulation. These results raise the possibility of a role for rt11beta-HSD in the protection of developing gonads from the inhibitory effects of stress-induced cortisol.

Longitudinal analyses of the steroid metabolome in obese PCOS girls with weight loss.

Science.gov (United States)

Reinehr, Thomas; Kulle, Alexandra; Rothermel, Juliane; Knop-Schmenn, Caroline; Lass, Nina; Bosse, Christina; Holterhus, Paul-Martin

2017-05-01

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. 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. 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. 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. 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. © 2017 The authors.

Adaptive and maladaptive cortisol responses to pediatric obesity.

Science.gov (United States)

Soros, Arlette; Zadik, Zvi; Chalew, Stuart

2008-09-01

The recent unprecedented increase of childhood obesity has led to an alarming rise in type 2 diabetes mellitus (T2D) among these children. The process underlying the progression from simple obesity to T2D is not well understood. Cortisol is a candidate factor in the pathogenesis of T2D, as it can exacerbate insulin resistance and provoke other disturbances of the metabolic syndrome. The 24-h integrated concentration (IC) of cortisol is suppressed in non-diabetic obese children compared to lean children. This difference in IC-cortisol is not due to changes in cortisol binding globulin or plasma cortisol to cortisone ratio between groups. In obese individuals, IC-cortisol suppression disappears with age after adolescence, which corresponds with increasing occurrence of T2D and other metabolic disorders of obesity. We consider the IC-cortisol levels of lean insulin sensitive children to be metabolically inappropriate for obese insulin resistant children. Thus, we hypothesize that suppression of IC-cortisol is an important adaptive response to obesity (cortisol adaptive suppression) in childhood that prevents pediatric T2D while failure to suppress IC-cortisol (cortisol suppression failure) exacerbates insulin resistance and contributes to the development of T2D. In further support of this hypothesis is early pilot data suggesting that cortisol suppression failure occurs in obese children with impaired fasting glucose levels. The mechanism(s) underlying cortisol adaptive suppression, how and why these mechanism(s) fail are unknown. Elucidation of these mechanisms may lead to interventions to prevent the development of T2D and its complications in obese individuals.

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.)

Expression of 11beta-hydroxysteroid dehydrogenase 1 and 2 in subcutaneous adipose tissue of lean and obese women with and without polycystic ovary syndrome.

Science.gov (United States)

Svendsen, P F; Madsbad, S; Nilas, L; Paulsen, S K; Pedersen, S B

2009-11-01

To investigate the expression of 11beta-hydroxysteroid dehydrogenase (11beta-HSD) type 1 and 2 and hexose-6-phosphate dehydrogenase (H6PDH) mRNA in subcutaneous abdominal tissue from lean and obese women with and without polycystic ovary syndrome (PCOS), and to investigate the association between these enzymes and different measures of insulin sensitivity. Cross-sectional study. A total of 60 women, 36 women with PCOS, 17 lean (lean PCOS, LP) and 19 obese (obese PCOS, OP) and 24 age- and weight-matched control women, 8 lean (lean controls, LC) and 16 obese (obese controls, OC). Subcutaneous adipose tissue was collected from the abdomen. Peripheral insulin sensitivity was assessed by the euglycemic hyperinsulinemic clamp and determined as glucose disposal rate and insulin sensitivity index. Whole-body insulin sensitivity was calculated using homeostasis model assessment insulin resistance index. Body composition was evaluated by dual X-ray absorptiometry. Adipose mRNA expression of leptin and adiponectin were determined by real-time PCR. Polycystic ovary syndrome (PPCOS or obesity on11beta-HSD2 or H6PDH mRNA expression. Decreased peripheral insulin sensitivity (P<0.001) and increased upper body fat distribution (P<0.01) were associated with increased expression of 11beta-HSD1, but neither 11beta-HSD2 nor H6PDH. Polycystic ovary syndrome and obesity are independently associated with increased expression of 11beta-HSD1. This may lead to increased conversion of cortisone to cortisol in the peripheral adipose tissue and subsequently increased glucocorticoid activity. Decreased peripheral insulin sensitivity and central obesity was associated with increased expression of 11beta-HSD1.

Allogeneic Hematopoietic Stem Cell Transplantation in the Treatment of Human C1q Deficiency: The Karolinska Experience.

Science.gov (United States)

Olsson, Richard F; Hagelberg, Stefan; Schiller, Bodil; Ringdén, Olle; Truedsson, Lennart; Åhlin, Anders

2016-06-01

Human C1q deficiency is associated with systemic lupus erythematosus (SLE) and increased susceptibility to severe bacterial infections. These patients require extensive medical therapy and some develop treatment-resistant disease. Because C1q is produced by monocytes, it has been speculated that allogeneic hematopoietic stem cell transplantation (allo-HSCT) may cure this disorder. We have so far treated 5 patients with C1q deficiency. In 3 cases, SLE symptoms remained relatively mild after the start of medical therapy, but 2 patients developed treatment-resistant SLE, and we decided to pursue treatment with allo-HSCT. For this purpose, we chose a conditioning regimen composed of treosulfan (14 g/m) and fludarabine (30 mg/m) started on day -6 and given for 3 and 5 consecutive days, respectively. Thymoglobulin was given at a cumulative dose of 8 mg/kg, and graft-versus-host disease prophylaxis was composed of cyclosporine and methotrexate. A 9-year-old boy and a 12-year-old girl with refractory SLE restored C1q production after allo-HSCT. This resulted in normal functional properties of the classical complement pathway followed by reduced severity of SLE symptoms. The boy developed posttransplant lymphoproliferative disease, which resolved after treatment with rituximab and donor lymphocyte infusion. Unfortunately, donor lymphocyte infusion induced severe cortisone-resistant gastrointestinal graft-versus-host disease, and the patient died from multiple organ failure 4 months after transplantation. The girl is doing well 33 months after transplantation, and clinically, all signs of SLE have resolved. Allo-HSCT can cure SLE in human C1q deficiency and should be considered early in subjects resistant to medical therapy.

Protective effects of carbenoxolone, an 11β-HSD1 inhibitor, against chemical induced dry eye syndrome.

Science.gov (United States)

Na, Yoon-Ju; Choi, Kyoung-Jin; Park, Sung Bum; Sung, Hye-Rim; Jung, Won Hoon; Kim, Hee Youn; Rhee, Sang Dal; Kim, Ki Young

2017-11-01

Dry eye syndrome (DES) is a disorder of the eye due to tear deficiency or excessive evaporation that causes damage to the eye and is associated with discomfort and dryness. 11β-Hydroxysteroid dehydrogenase 1 (11β-HSD1) is an enzyme that converts inactive cortisone to active cortisol. Recently, 11β-HSD1 has been expressed in human and rodent eyes and has been recognized as a target of glaucoma. In this study, the therapeutic effects and underlying mechanisms of topical carbenoxolone, an 11β-HSD1 inhibitor, were investigated in benzalkonium chloride (BAC)-treated human conjunctival epithelial cells and a rat DES model. In the in vitro study, carbenoxolone dose-dependently inhibited cell death and 11β-HSD1 activity in BAC-treated human conjunctival epithelial cells. For the in vivo study, carbenoxolone or a solvent was administered to the BAC-induced DES model twice daily. BAC-treated rat eyes showed significant increases in ocular surface damage, a reduction of tears, decrease corneal thickness, corneal basement membrane destruction, apoptosis in the conjunctival epithelium, and expression of pro-inflammatory cytokines (TNF-α and IL-6) and 11β-HSD1. These effects of BAC were reversed by topical carbenoxolone treatment. These results demonstrate that carbenoxolone can prevent DES by inhibiting pro-inflammatory cytokine expression and cell death of the corneal and conjunctival epithelium via inhibition of both 11β-HSD1 activity and expression in the eyes of BAC-treated rats. It is suggested that topical 11β-HSD1 inhibitors may provide a new therapeutic window in the prevention and/or treatment of DES.

Differential effect of adrenocorticosteroids on 11 beta-hydroxysteroid dehydrogenase bioactivity at the anterior pituitary and hypothalamus in rats.

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Idrus, R B; Mohamad, N B; Morat, P B; Saim, A; Abdul Kadir, K B

1996-08-01

11 beta-Hydroxysteroid dehydrogenase (11 beta-OHSD) is a microsomal enzyme that catalyzes the dehydrogenation of cortisol (F) to cortisone (E) in man and corticosterone (B) to 11-dehydrocorticosterone (A) in rats. 11 beta-OHSD has been identified in a wide variety of tissues. The differential distribution of 11 beta-OHSD suggests that this enzyme has locally defined functions that vary from region to region. The aim of this study was to investigate the effects of the glucocorticoids B and dexamethasone (DM), the mineralocorticoid deoxycorticosterone (DOC), and the inhibitors of 11 beta-OHSD glycyrrhizic acid (Gl) and glycyrrhetinic acid (GE) on 11 beta-OHSD bioactivity at the hypothalamus (HT) and anterior pituitary (AP). Male Wistar rats were treated with GI or were adrenalectomized (ADX) and treated with either B, DM, or DOC for 7 days. All treatments were in vivo except GE, which was used in vitro. At the end of treatment, homogenates of HT and AP were assayed for 11 beta-OHSD bioactivity, expressed as the percentage conversion of B to A in the presence of NADP, 11 beta-OHSD bioactivity is significantly higher (P < 0.0001) in the AP compared with the HT. Adrenalectomy significantly increased the enzyme activity in the AP (P < 0.05), an effect reversed by B or DM. ADX rats treated with DOC showed decreased enzyme activity in the AP (P < 0.001) but increased the activity in the HT (P < 0.0001). Gl increased activity in both HT and AP, whereas GE decreased activity significantly. We conclude that the modulation of 11 beta-OHSD is both steroid specific and tissue specific.

Severe metabolic alkalosis, hypokalemia, and respiratory acidosis induced by the Chinese herbal medicine yokukansan in an elderly patient with muscle weakness and drowsiness.

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Yamada, Shunsuke; Tokumoto, Masanori; Kansui, Yasuo; Wakisaka, Yoshinobu; Uchizono, Yuji; Tsuruya, Kazuhiko; Ooboshi, Hiroaki

2013-05-01

Yokukansan is a Chinese herbal medicine containing licorice that has been shown to alleviate the behavioral and psychological symptoms of Alzheimer's disease, with few adverse effects. Increasing numbers of patients with Alzheimer's disease in Japan are now being treated with this drug. However, yokukansan should be used with caution because of its potential to induce pseudoaldosteronism through the inhibition of 11-beta-hydroxysteroid dehydrogenase type 2, which metabolizes cortisol into cortisone. We present the case of an 88-year-old woman with a history of Alzheimer's disease who was transferred to our emergency department because of drowsiness, anorexia, and muscle weakness. Her blood pressure was 168/90 mmHg. Laboratory data showed serum potassium of 1.9 mmol/l, metabolic alkalosis (pH 7.54; HCO 3 - , 50.5 mmol/l; chloride, 81 mmol/l; sodium, 140 mmol/l), and respiratory disorders (pCO 2 , 60.5 mmHg; pO 2 , 63.8 mmHg). Plasma renin activity and aldosterone concentration were suppressed, and urinary potassium excretion was 22 mmol/l (calculated transtubular potassium gradient 12.9). An electrocardiogram showed flat T-waves and U-waves with ventricular premature contractions. Echocardiography denied volume depletion. Medical interview disclosed that she had been treated with a Chinese herbal medicine (yokukansan) containing licorice. The final diagnosis was pseudoaldosteronism and respiratory acidosis induced by licorice. Hypokalemia, metabolic alkalosis, and respiratory acidosis all subsided shortly after the discontinuation of yokukansan and initiation of intravenous potassium replacement. This case highlights the need for nephrologists to consider the possible involvement of Chinese herbal medicines, including yokukansan, when they encounter hypokalemia in elderly patients.

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.

A Network Pharmacology Approach to Determine the Active Components and Potential Targets of Curculigo Orchioides in the Treatment of Osteoporosis.

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Wang, Nani; Zhao, Guizhi; Zhang, Yang; Wang, Xuping; Zhao, Lisha; Xu, Pingcui; Shou, Dan

2017-10-27

BACKGROUND Osteoporosis is a complex bone disorder with a genetic predisposition, and is a cause of health problems worldwide. In China, Curculigo orchioides (CO) has been widely used as a herbal medicine in the prevention and treatment of osteoporosis. However, research on the mechanism of action of CO is still lacking. The aim of this study was to identify the absorbable components, potential targets, and associated treatment pathways of CO using a network pharmacology approach. MATERIAL AND METHODS We explored the chemical components of CO and used the five main principles of drug absorption to identify absorbable components. Targets for the therapeutic actions of CO were obtained from the PharmMapper server database. Pathway enrichment analysis was performed using the Comparative Toxicogenomics Database (CTD). Cytoscape was used to visualize the multiple components-multiple target-multiple pathways-multiple disease network for CO. RESULTS We identified 77 chemical components of CO, of which 32 components could be absorbed in the blood. These potential active components of CO regulated 83 targets and affected 58 pathways. Data analysis showed that the genes for estrogen receptor alpha (ESR1) and beta (ESR2), and the gene for 11 beta-hydroxysteroid dehydrogenase type 1, or cortisone reductase (HSD11B1) were the main targets of CO. Endocrine regulatory factors and factors regulating calcium reabsorption, steroid hormone biosynthesis, and metabolic pathways were related to these main targets and to ten corresponding compounds. CONCLUSIONS The network pharmacology approach used in our study has attempted to explain the mechanisms for the effects of CO in the prevention and treatment of osteoporosis, and provides an alternative approach to the investigation of the effects of this complex compound.

The secretion, synthesis, and metabolism of cortisol and its downstream genes in the H-P-I axis of rare minnows (Gobiocypris rarus) are disrupted by acute waterborne cadmium exposure.

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Liu, Xiao-Hong; Xie, Bi-Wen; Wang, Zhi-Jian; Jin, Li; Zhang, Yao-Guang

2016-01-01

The H (hypothalamic)-P (pituitary)-I (interrenal) axis plays a critical role in the fish stress response and is regulated by several factors. Cadmium (Cd) is one of the most toxic heavy metals in the world, but its effects on the H-P-I axis of teleosts are largely unknown. Using rare minnow (Gobiocypris rarus) as an experimental animal, we found that Cd only disrupted the secretion and synthesis of cortisol. Neither hormones at the H or P level nor the expressions of their receptor genes (corticotropin-releasing hormone receptor (CRHR) and melanocortin receptor 2 (MC2R)) were affected. Steroidogenic acute regulator (StAR), CYP11A1 and CYP11B1, which encode the key enzymes in the cortisol synthesis pathway, were significantly up-regulated in the kidney (including the head kidney). The level of 11β-HSD2, which is required for the conversion of cortisol to cortisone, was increased in the kidney, intestine, brain, and hepatopancreas, whereas the expression of 11β-HSD1, which encodes the reverse conversion enzyme, was increased in the gill, kidney and almost unchanged in other tissues. The enzyme activity concentration of 11β-HSD2 was increased in the kidney as well. The level of glucocorticoid receptor (GR) decreased in the intestine, gill and muscle, and the key GR regulator FK506 binding protein5 (FKBP5) was up-regulated in the GR-decreased tissues, whereas the level of nuclear receptor co-repressor 1 (NCoR1), another GR regulator remained almost unchanged. Thus, GR, FKBP5 and 11β-HSD2 may be involved in Cd-induced cortisol disruption. Copyright © 2016 Elsevier Inc. All rights reserved.

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.

Employment of the H{sup 3}-Progesterone in the Examination of the Synthesis of 17-OH-Corticosteroids by Human Placental Tissue; Emploi de la Progesterone Tritiee Pour L'etude de la Synthese des Steroiedes Surrenaux et Placentaires; 0418 0441 0414 ; Empleo de la Progesterone Tritiada en el Estudio de la Sintesis de Esteroides Suprarrenales y Placentarios

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Polvani, F.; Roversi, G. D.; Silvestrini, R. [Clinica Ostetrica E Ginecologica dell' Universita di Milano Laboratorio di Microbiologia E Chemioterapia ' ' Farmitalia' ' , Milano (Italy)

1962-02-15

Tritium-labelled progesterone, as a precursor of the 17-OH-corticosteroids, was used to study the biosynthesis of placental and adrenal steroids. Homogenates from cattle adrenals were incubated with H{sup 3}-progesterone for 3 h in an O{sub 2} atmosphere. Then corticosteroids were extracted according to Meyer's method and chromatographically prepared in Forisil columns and delta 4-3-ketosteroids were localized on chromatographic paper. The latter was soaked in a nuclear emulsion (Ilford K2 ''gel form'') and was kept at 4 Degree-Sign C for 21 d, allowing the formation of H{sup 3}-cortisone, H{sup 3}-cortisol and of other steroidal-compounds while the photographic development was made evident. The same incubation technique was used in the research on placental homogenates which revealed the radioactivity of recently produced 11-OH-corticoids by means of a gas-filling counter of the single chromatographic spots. (author) [French] On a employe la progesterone tritiee comme precurseur des 17-hydroxycorticosteroiedes, pour etudier la biosynthese des steroiedes placentaires et surrenaux. On a incube, avec la progesterone tritiee, pendant trois heures, dans une atmosphere de O{sub 2} , des: homogenats provenant de capsules surrenales de bovins. Apres avoir extrait les corticosteroiedes par le procede Meyer, on les a isoles par chromatographic dans des colonnes de florisil et l'on a localise les {Delta}-4-3 cetosteroiedes par chromatographic sur papier. Ces chromatographies ont ete ensuite immergees dans une emulsion nucleaire (Ilford K 2 'gel form') et maintenues pendant 21 jours a une temperature de 4 Degree-Sign C pour permettre l'identification de cortisone tritiee, de Cortisol tritie et d'autres steroiedes au cours du processus photographique. On a utilise la meme methode d'incubation pour la recherche sur des homogenats placentaires; l'examen des taches chromatographiques a l'aide d'un compteur a atmosphere gazeuse a revele la radioactivite des 11-hydroxycorticoiedes

Bone marrow-derived thymic antigen-presenting cells determine self-recognition of Ia-restricted T lymphocytes

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Longo, D.L.; Kruisbeek, A.M.; Davis, M.L.; Matis, L.A.

1985-01-01

The authors previously have demonstrated that in radiation-induced bone marrow chimeras, T-cell self-Ia restriction specificity appeared to correlate with the phenotype of the bone marrow-derived antigen-presenting (or dendritic) cell in the thymus during T-cell development. However, these correlations were necessarily indirect because of the difficulty in assaying thymic function directly by adult thymus transplant, which has in the past been uniformly unsuccessful. They now report success in obtaining functional T cells from nude mice grafted with adult thymuses reduced in size by treatment of the thymus donor with anti-thymocyte globulin and cortisone. When (B10 Scn X B10.D2)F1 nude mice (I-Ab,d) are given parental B10.D2 (I-Ad) thymus grafts subcutaneously, their T cells are restricted to antigen recognition in association with I-Ad gene products but not I-Ab gene products. Furthermore, thymuses from (B10 X B10.D2)F1 (I-Ab,d)----B10 (I-Ab) chimeras transplanted 6 months or longer after radiation (a time at which antigen-presenting cell function is of donor bone marrow phenotype) into (B10 X B10.D2)F1 nude mice generate T cells restricted to antigen recognition in association with both I-Ad and I-Ab gene products. Thymuses from totally allogeneic bone marrow chimeras appear to generate T cells of bone marrow donor and thymic host restriction specificity. Thus, when thymus donors are radiation-induced bone marrow chimeras, the T-cell I-region restriction of the nude mice recipients is determined at least in part by the phenotype of the bone marrow-derived thymic antigen presenting cells or dendritic cells in the chimeric thymus

Doctor Guillermo García López (1905-1956, gran diabetólogo cubano Doctor Guillermo García López (1905-1956, a great cuban diabetologist

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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.

Decreased 11β-Hydroxysteroid Dehydrogenase 1 Level and Activity in Murine Pancreatic Islets Caused by Insulin-Like Growth Factor I Overexpression.

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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.

Glucocorticoids for the treatment of post-traumatic stress disorder and phobias: a novel therapeutic approach.

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de Quervain, Dominique J-F; Margraf, Jürgen

2008-04-07

Post-traumatic stress disorder (PTSD) and phobias belong to the most common anxiety disorders and to the most common psychiatric illnesses in general. In both disorders, aversive memories are thought to play an important role in the pathogenesis and symptomatology. Previously, we have reported that elevated glucocorticoid levels inhibit memory retrieval in animals and healthy humans. We therefore hypothesized that the administration of glucocorticoids might also inhibit the retrieval of aversive memory, thereby reducing symptoms in patients with PTSD and phobias. In recent clinical studies, we found first evidence to support this hypothesis. In patients with PTSD, low-dose cortisol treatment for one month reduced symptoms of traumatic memories without causing adverse side effects. Furthermore, we found evidence for a prolonged effect of the cortisol treatment. Persistent retrieval and reconsolidation of traumatic memories is a process that keeps these memories vivid and thereby the disorder alive. By inhibiting memory retrieval, cortisol may weaken the traumatic memory trace, and thus reduce symptoms even beyond the treatment period. In patients with social phobia, we found that a single oral administration of cortisone 1 h before a socio-evaluative stressor significantly reduced self-reported fear during the anticipation-, exposure-, and recovery phase of the stressor. In subjects with spider phobia, repeated oral administration of cortisol 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 two days after the last cortisol administration, indicating that cortisol facilitated the extinction of phobic fear. In conclusion, by a common mechanism of reducing the retrieval of aversive memories, glucocorticoids may be suited for the treatment of PTSD as well as phobias. More studies are needed to further evaluate the therapeutic efficacy of

Epicondilite lateral do cotovelo Lateral epicondylitis of the elbow

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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.

Pulmonary function following adjuvant chemotherapy and radiotherapy for breast cancer and the issue of three-dimensional treatment planning

International Nuclear Information System (INIS)

Lind, P.A.R.M.; Glas, U.; Fornander, T.; Rosfors, S.; Bevegard, S.; Wennberg, B.

1998-01-01

Background and purpose: The frequency and grade of pulmonary complications following adjuvant radiotherapy for breast cancer are still debated. This study focuses on loss of pulmonary function. Materials and methods: We have measured the reduction of pulmonary function 5 months following radiotherapy in 144 node-positive stage II breast cancer patients by using pulmonary function tests. Results: No deterioration of pulmonary function was detected among the patients who were treated with local radiotherapy. On the contrary, there was a mean increase in diffusion capacity by 7% (P=0.004) following radiotherapy, which most likely was explained by the adjuvant chemotherapy administered prior to the baseline pulmonary function tests. Patients undergoing loco-regional radiotherapy showed a mean reduction in diffusion capacity by 5% (P<0.001) and in vital capacity by 3% (P=0.001). The subset of patients (9%) who were diagnosed with severe pulmonary complications needing cortisone treatment had significantly larger mean paired differences in vital capacity (-0.446 L, -15% (equivalent to 15 years of normal ageing or the loss of 3/4 of a lung lobe)) compared to the patients who were asymptomatic (-0.084 L) (P<0.05). When the effects of potential confounding factors and different radiotherapy techniques were tested on the reduction of pulmonary function by stepwise multiple regression analysis, a significant correlation was found only to loco-regional radiotherapy including the lower internal mammary lymph nodes. Conclusions: We conclude that a clinically important reduction of pulmonary function is seen in the subset of patients who are diagnosed with severe pulmonary complication following loco-regional radiotherapy for breast cancer. The results of this study warrant further studies based on individual lung dose volume histograms. (Copyright (c) 1998 Elsevier Science B.V., Amsterdam. All rights reserved.)

Identification of altered metabolic pathways in plasma and CSF in mild cognitive impairment and Alzheimer's disease using metabolomics.

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Eugenia Trushina

Full Text Available Alzheimer's Disease (AD currently affects more than 5 million Americans, with numbers expected to grow dramatically as the population ages. The pathophysiological changes in AD patients begin decades before the onset of dementia, highlighting the urgent need for the development of early diagnostic methods. Compelling data demonstrate that increased levels of amyloid-beta compromise multiple cellular pathways; thus, the investigation of changes in various cellular networks is essential to advance our understanding of early disease mechanisms and to identify novel therapeutic targets. We applied a liquid chromatography/mass spectrometry-based non-targeted metabolomics approach to determine global metabolic changes in plasma and cerebrospinal fluid (CSF from the same individuals with different AD severity. Metabolic profiling detected a total of significantly altered 342 plasma and 351 CSF metabolites, of which 22% were identified. Based on the changes of >150 metabolites, we found 23 altered canonical pathways in plasma and 20 in CSF in mild cognitive impairment (MCI vs. cognitively normal (CN individuals with a false discovery rate <0.05. The number of affected pathways increased with disease severity in both fluids. Lysine metabolism in plasma and the Krebs cycle in CSF were significantly affected in MCI vs. CN. Cholesterol and sphingolipids transport was altered in both CSF and plasma of AD vs. CN. Other 30 canonical pathways significantly disturbed in MCI and AD patients included energy metabolism, Krebs cycle, mitochondrial function, neurotransmitter and amino acid metabolism, and lipid biosynthesis. Pathways in plasma that discriminated between all groups included polyamine, lysine, tryptophan metabolism, and aminoacyl-tRNA biosynthesis; and in CSF involved cortisone and prostaglandin 2 biosynthesis and metabolism. Our data suggest metabolomics could advance our understanding of the early disease mechanisms shared in progression from CN to

Upregulation of adipose 11-beta-hydroxysteroid dehydrogenase type 1 expression in ovariectomized rats is due to obesity rather than lack of estrogen.

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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 < 0.05). 11beta-HSD1 expression in the (OVX+E)-group was significantly reduced compared with the nonsubstituted group (P < 0.05). 11beta-HSD1 expression in the (OVX-E+D)-group was reduced significantly (P < 0.05) when compared with the level of the estrogen-substituted group. No significant differences between the control group, the (OVX+E)-group, and the (OVX-E+D)-group were found. In the in vitro studies, no direct 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.

Accuracy of immunoassay and mass spectrometry urinary free cortisol in the diagnosis of Cushing's syndrome.

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Aranda, G; Careaga, M; Hanzu, F A; Patrascioiu, I; Ríos, P; Mora, M; Morales-Romero, B; Jiménez, W; Halperin, I; Casals, G

2016-10-01

Urinary free cortisol (UFC) determination by highly specific methods as mass spectrometry instead of commercially available antibody-based immunoassays is increasingly recommended. However, clinical comparisons of both analytical approaches in the screening of Cushing's syndrome (CS) are not available. The aim of this study was to evaluate the diagnostic value of mass spectrometry versus immunoassay measurements of 24 h-UFC in the screening of CS. Cross-sectional study of 33 histologically confirmed CS patients: 25 Cushing's disease, 5 adrenal CS and 3 ectopic CS; 92 non-CS patients; and 35 healthy controls. UFC by immunoassay (UFCxIA) and mass spectrometry (UFCxMS), urinary free cortisone (UFCo) and UFC:UFCo ratio were measured, together with creatinine-corrected values. Sensitivity, specificity, AUC and Landis and Koch concordance index were determined. AUC for UFCxIA and UFCxMS were 0.77 (CI 0.68-0.87) and 0.77 (CI 0.67-0.87) respectively, with a kappa coefficient 0.60 and strong Landis and Koch concordance index. The best calculated cutoff values were 359 nmol/24 h for UFCxIA (78 % sensitivity, 62 % specificity) and 258.1 nmol/24 h for UCFxMS (53 % sensitivity, 86 % specificity). The upper limit of UFCxIA and UCFxMS reference ranges were 344.7 and 169.5 nmol/24 h respectively. Sensitivity and specificity for CS diagnosis at these cutpoints were 84 and 56 % for UFCxIA and 81 and 54 % for UFCxMS. According to our data, both methods present a very similar diagnostic value. However, results suggest that lower cutoff points for mass spectrometry may be necessary in order to improve clinical sensitivity.

A validated analytical method to study the long-term stability of natural and synthetic glucocorticoids in livestock urine using ultra-high performance liquid chromatography coupled to Orbitrap-high resolution mass spectrometry.

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De Clercq, Nathalie; Julie, Vanden Bussche; Croubels, Siska; Delahaut, Philippe; Vanhaecke, Lynn

2013-08-02

Due to their growth-promoting effects, the use of synthetic glucocorticoids is strictly regulated in the European Union (Council Directive 2003/74/EC). In the frame of the national control plans, which should ensure the absence of residues in food products of animal origin, in recent years, a higher frequency of prednisolone positive bovine urines has been observed. This has raised questions with respect to the stability of natural corticoids in the respective urine samples and their potential to be transformed into synthetic analogs. In this study, a ultra high performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS) methodology was developed to examine the stability of glucocorticoids in bovine urine under various storage conditions (up to 20 weeks) and to define suitable conditions for sample handling and storage, using an Orbitrap Exactive™. To this end, an extraction procedure was optimized using a Plackett-Burman experimental design to determine the key conditions for optimal extraction of glucocorticoids from urine. Next, the analytical method was successfully validated according to the guidelines of CD 2002/657/EC. Decision limits and detection capabilities for prednisolone, prednisone and methylprednisolone ranged, respectively, from 0.1 to 0.5μgL(-1) and from 0.3 to 0.8μgL(-1). For the natural glucocorticoids limits of detection and limits of quantification for dihydrocortisone, cortisol and cortisone ranged, respectively, from 0.1 to 0.2μgL(-1) and from 0.3 to 0.8μgL(-1). The stability study demonstrated that filter-sterilization of urine, storage at -80°C, and acidic conditions (pH 3) were optimal for preservation of glucocorticoids in urine and able to significantly limit degradation up to 20 weeks. Copyright © 2013 Elsevier B.V. All rights reserved.

Liver upregulation of genes involved in cortisol production and action is associated with metabolic syndrome in morbidly obese patients.

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Torrecilla, Esther; Fernández-Vázquez, Gumersindo; Vicent, David; Sánchez-Franco, Franco; Barabash, Ana; Cabrerizo, Lucio; Sánchez-Pernaute, Andrés; Torres, Antonio J; Rubio, Miguel Angel

2012-03-01

Hepatic 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) activity, which converts cortisone (inactive) to cortisol, is downregulated in obesity. However, this compensation fails in obese with metabolic abnormalities, such as diabetes. To further characterize the tissue-specific cortisol regeneration in obesity, we have investigated the mRNA expression of genes related to local cortisol production, i.e., 11β-HSD1, hexose-6-phosphate dehydrogenase (H6PDH) and cortisol action, glucocorticoid receptor (GR) and a cortisol target gene, phosphoenolpyruvate carboxykinase (PEPCK) in the liver, and visceral (VAT) and subcutaneous (SAT) adipose tissues from morbidly obese patients with and without metabolic syndrome (MS). Fifty morbidly obese patients undergoing bariatric surgery, 14 men (mean age, 41.3 ± 3.5 years; BMI, 48.0 ± 3.6 kg/m(2)) and 36 women (mean age, 44.6 ± 1.9 years; BMI, 44.9 ± 1.2 kg/m(2)), were classified as having MS (MS+, n = 20) or not (MS-, n = 30). Tissue mRNA levels were measured by real-time polymerase chain reaction. Hepatic mRNA levels of these genes were higher in obese patients with MS (11β-HSD1, P = 0.002; H6PDH, P = 0.043; GR, P = 0.033; PEPCK, P = 0.032) and positively correlated with the number of clinical characteristics that define the MS. The expression of the four genes positively correlated among them. In contrast to the liver, these genes were not differently expressed in VAT or SAT, when MS+ and MS- obese patients were compared. Coordinated liver-specific upregulation of genes involved in local cortisol regeneration and action support the concept that local hepatic hypercortisolism contributes to development of MS in morbidly obese patients.

Platelet-rich plasma for chronic lateral epicondylitis: is one injection sufficient?

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Glanzmann, Michael C; Audigé, Laurent

2015-12-01

Chronic lateral epicondylitis is generally treated using nonsurgical methods including physiotherapy and infiltrations of cortisone or platelet-rich plasma (PRP). The latter is known for its simple application as well as associated low risk of adverse events, which lend to its widespread use in treating various musculoskeletal conditions. There is limited evidence on the effectiveness of PRP injections to optimally treat chronic lateral epicondylitis. This study explored the effectiveness of single or repeated injections for patients with symptoms that spanned 6 months or more and were unresponsive to alternate conservative measures. Patients with chronic lateral epicondylitis received PRP injections in 4-week intervals that were complemented with standardized physical therapy. Patient-reported outcomes based on the patient-rated elbow evaluation (PREE), quick disabilities of the arm, shoulder and hand (qDASH), and EuroQol (five dimensions) 3-level version (EQ5D3L) questionnaires were documented at each visit including 6 months after the first injection. These outcomes were compared between patients receiving 1 vs. 2 or 3 PRP injections. Sixty-two patients received one (n = 36) or more (n = 26) PRP injections. The mean baseline to 6-month follow-up scores of the PREE and qDASH questionnaires improved significantly from 54.0 to 23.0 and 50.3 to 20.7, respectively. The mean baseline EQ5D3L-visual analogue scale score improved from 62.5 to 82.9 by 6 months post-injection. These outcomes did not significantly differ between the patients who received varying numbers of injections. Patients with chronic lateral epicondylitis reported significant pain relief and gain in function as well as quality of life 6 months after localized PRP treatment. A single PRP injection may be sufficient.

11β-Hydroxysteroid Dehydrogenases: Intracellular Gate-Keepers of Tissue Glucocorticoid Action

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Chapman, Karen; Holmes, Megan

2013-01-01

Glucocorticoid action on target tissues is determined by the density of “nuclear” receptors and intracellular metabolism by the two isozymes of 11β-hydroxysteroid dehydrogenase (11β-HSD) which catalyze interconversion of active cortisol and corticosterone with inert cortisone and 11-dehydrocorticosterone. 11β-HSD type 1, a predominant reductase in most intact cells, catalyzes the regeneration of active glucocorticoids, thus amplifying cellular action. 11β-HSD1 is widely expressed in liver, adipose tissue, muscle, pancreatic islets, adult brain, inflammatory cells, and gonads. 11β-HSD1 is selectively elevated in adipose tissue in obesity where it contributes to metabolic complications. Similarly, 11β-HSD1 is elevated in the ageing brain where it exacerbates glucocorticoid-associated cognitive decline. Deficiency or selective inhibition of 11β-HSD1 improves multiple metabolic syndrome parameters in rodent models and human clinical trials and similarly improves cognitive function with ageing. The efficacy of inhibitors in human therapy remains unclear. 11β-HSD2 is a high-affinity dehydrogenase that inactivates glucocorticoids. In the distal nephron, 11β-HSD2 ensures that only aldosterone is an agonist at mineralocorticoid receptors (MR). 11β-HSD2 inhibition or genetic deficiency causes apparent mineralocorticoid excess and hypertension due to inappropriate glucocorticoid activation of renal MR. The placenta and fetus also highly express 11β-HSD2 which, by inactivating glucocorticoids, prevents premature maturation of fetal tissues and consequent developmental “programming.” The role of 11β-HSD2 as a marker of programming is being explored. The 11β-HSDs thus illuminate the emerging biology of intracrine control, afford important insights into human pathogenesis, and offer new tissue-restricted therapeutic avenues. PMID:23899562

Mechanized Sephadex LH-20 multiple column chromatography as a prerequisite for automated multi-steroid radioimmunoassays

International Nuclear Information System (INIS)

Sippell, W.G.; Bidlingmaier, F.; Knorr, D.

1978-01-01

To establish a procedure for the simultaneous determination of all major corticosteroid hormones and their immediate biological precursors in the same plasma sample, two different mechanized methods for the simultaneous isolation of aldosterone (A), corticosterone (B), 11-deoxycorticosterone (DOC), progesterone (P), 17-hydroxyprogesterone (17-OHP), 11-deoxycortisol (S), cortisol (F) and cortisone (E) from the methylene chloride extracts of 0.1 to 2.0ml plasma samples have been developed. In method I, steroids are separated with methylene chloride:methanol=98:2 as solvent system on 60-cm Sephadex LH-20 columns, up to eight of which are eluted in parallel using a multi-channel peristaltic pump and individual flow-rate control (40ml/h) by capillary valves and micro-flowmeters. Method II, on the other hand, utilizes the same solvent system on ten 75-cm LH-20 columns which are eluted in reversed flow simultaneously by a ten-channel, double-piston pump that precisely maintains an elution flow rate of 40ml/h in every column. In both methods, eluate fractions of each of the isolated steroids are automatically pooled and collected from all parallel columns by one programmable linear fraction collector. As a result of the high reproducibility of the elution patterns, both between different parallel columns and between 30 to 40 consecutive elutions, mean recoveries of tritiated steroids including extraction are 60 to 84% after a single separation and still over 50% after an additional separation on 40-cm LH-20 columns, with coefficients of variation below 15% (method II). Thus, the eight steroids can be completely isolated from each of ten plasma extracts within 3 to 4 hours, yielding 80 samples readily prepared for subsequent quantitation by radioimmunoassay. (author)

Elevation of 11β-hydroxysteroid dehydrogenase type 2 activity in Holocaust survivor offspring: evidence for an intergenerational effect of maternal trauma exposure.

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Bierer, Linda M; Bader, Heather N; Daskalakis, Nikolaos P; Lehrner, Amy L; Makotkine, Iouri; Seckl, Jonathan R; Yehuda, Rachel

2014-10-01

Adult offspring of Holocaust survivors comprise an informative cohort in which to study intergenerational transmission of the effects of trauma exposure. Lower cortisol and enhanced glucocorticoid sensitivity have been previously demonstrated in Holocaust survivors with PTSD, and in offspring of Holocaust survivors in association with maternal PTSD. In other work, reduction in the activity of the enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD-2), which inactivates cortisol, was identified in Holocaust survivors in comparison to age-matched, unexposed Jewish controls. Therefore, we investigated glucocorticoid metabolism in offspring of Holocaust survivors to evaluate if similar enzymatic decrements would be observed that might help to explain glucocorticoid alterations previously shown for Holocaust offspring. Holocaust offspring (n=85) and comparison subjects (n=27) were evaluated with clinical diagnostic interview and self-rating scales, and asked to collect a 24-h urine sample from which concentrations of cortisol and glucocorticoid metabolites were assayed by GCMS. 11β-HSD-2 activity was determined as the ratio of urinary cortisone to cortisol. Significantly reduced cortisol excretion was observed in Holocaust offspring compared to controls (p=.046), as had been shown for Holocaust survivors. However, 11β-HSD-2 activity was elevated for offspring compared to controls (p=.008), particularly among those whose mothers had been children, rather than adolescents or adults, during World War II (p=.032). The effect of paternal Holocaust exposure could not be reliably investigated in the current sample. The inverse association of offspring 11β-HSD-2 activity with maternal age at Holocaust exposure is consistent with the influence of glucocorticoid programming. Whereas a long standing reduction in 11β-HSD-2 activity among survivors is readily interpreted in the context of Holocaust related deprivation, understanding the directional effect on offspring will

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.

Multisteroid LC–MS/MS assay for glucocorticoids and androgens and its application in Addison's disease

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Methlie, Paal; Hustad, Steinar; Kellman, Ralf; Almås, Bjørg; Erichsen, Martina M; Husebye, Eystein S; Løvås, Kristian

2013-01-01

Objective Liquid chromatography–tandem mass spectrometry (LC–MS/MS) offers superior analytical specificity compared with immunoassays, but it is not available in many regions and hospitals due to expensive instrumentation and tedious sample preparation. Thus, we developed an automated, high-throughput LC–MS/MS assay for simultaneous quantification of ten endogenous and synthetic steroids targeting diseases of the hypothalamic–pituitary–adrenal axis and gonads. Methods Deuterated internal standards were added to 85 μl serum and processed by liquid–liquid extraction. Cortisol, cortisone, prednisolone, prednisone, 11-deoxycortisol, dexamethasone, testosterone, androstenedione and progesterone were resolved by ultra-high-pressure chromatography on a reversed-phase column in 6.1 min and detected by triple-quadrupole mass spectrometry. The method was used to assess steroid profiles in women with Addison's disease (AD, n=156) and blood donors (BDs, n=102). Results Precisions ranged from 4.5 to 10.1% relative standard deviations (RSD), accuracies from 95 to 108% and extraction recoveries from 60 to 84%. The method was practically free of matrix effects and robust to individual differences in serum composition. Most postmenopausal AD women had extremely low androstenedione concentrations, below 0.14 nmol/l, and median testosterone concentrations of 0.15 nmol/l (interquartile range 0.00–0.41), considerably lower than those of postmenopausal BDs (1.28 nmol/l (0.96–1.64) and 0.65 nmol/l (0.56–1.10) respectively). AD women in fertile years had androstenedione concentrations of 1.18 nmol/l (0.71–1.76) and testosterone concentrations of 0.44 nmol/l (0.22–0.63), approximately half of those found in BDs of corresponding age. Conclusion This LC–MS/MS assay provides highly sensitive and specific assessments of glucocorticoids and androgens with low sample volumes and is suitable for endocrine laboratories and research. Its utility has been

Urinary Steroid Profile in Ironman Triathletes

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Marcos-Serrano Marta

2018-03-01

Full Text Available The aim of this study was to determine variations in the urinary steroid profile of triathletes following an Ironman event. A total of 10 male participants (age = 36.0 ± 1.27 years; body height = 179.29 ± 10.77 cm; body mass = 74.50 ± 1.04 kg completed an Ironman Championship. Urine samples were collected before, immediately after, and 24 hours following the race. Gas chromatography-mass spectrometry (GC/MS was used to detect and quantify catabolic and anabolic hormones: Androsterone, Dehydroepiandrosteone (DHEA, Androstenedione and Testosterone (T, Betaestradiol, Estrone, Progesterone, Cortisol (C, Cortisone, Tetrahydrocortisol (THE and Tetrahydrocortisone (THF. These were measured in their glucuroconjugated and free forms. Androsterone (3297.80 ± 756.83 vs. 2154.26 ± 1375.38, DHEA (47.80 ± 19.21 vs. 32.62 ± 15.96 and Beta-estradiol (59.36 ± 11.7 vs. 41.67 ± 10.59 levels decreased after the event. The significant decrease of DHEA (47.80 ± 19.21 vs. 32.11 ± 14.03 remained at 24 hours. Cortisol (200.38 ± 56.60 vs. 257.10 ± 74.00 and THE (238.65 ± 81.55 vs. 289.62 ± 77.13 increased after exercise and remained elevated 24 hours later (200.38 ± 56.60 vs. 252.48 ± 62.09; 238.65 ± 81.55 vs. 284.20 ± 66.66. The following anabolic/catabolic ratios fell after exercise: T/C (0.85 ± 0.54 vs. 0.54 ± 0.29, T/THE (0.66 ± 0.29 vs. 0.40 ± 0.08, T/THE+THF (0.38 ± 0.17 vs. 0.24 ± 0.06, DHEA/THE (0.22 ± 0.05 vs. 0.12 ± 0.05, DHEA/THF (0.34 ± 0.02 vs. 0.21 ± 0.01 and DHEA/THE+THF (0.12 ± 0.02 vs. 0.08 ± 0.03. The steroid profile showed that athletes were fatigued after finishing the competition and a catabolic state remained 24 hours later.

Recovery of HPA Axis Function After Successful Gonadotropin-Induced Pregnancy and Delivery in a Woman With Panhypopituitarism: Case Report and Review.

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Wang, Yi; Zhang, Qiongyue; Yang, Jianzhi; Zhao, Xiaolong; He, Min; Shou, Xuefei; Li, Shiqi; Li, Yiming; Wang, Yongfei; Ye, Hongying

2015-09-01

Hypopituitarism is defined as the partial or complete defect of anterior pituitary hormone secretion. Patients with hypopituitarism usually need life-long hormone replacement therapy. However, in this case, we report a patient with panhypopituitarism whose hypothalamus-pituitary-adrenal (HPA) axis function was completely recovered after pregnancy and delivery. In this case study, we reported the case management and conducted a review of literature to identify the possible mechanism of pituitary function recovery. The patient who suffered from secondary amenorrhea was found a nonfunctioning pituitary macroadenoma, and the hormone test showed serum cortisol, FT3, FT4, thyrotropic hormone, and prolactin were at normal range. After surgical removal of the tumor which invasion in the sellar region, the patient had panhypopituitarism confirmed by the routine hormone test. Though spontaneous pregnancy is impossible in female patients with panhypopituitarism, the patient was restored fertility by the help of artificial reproductive techniques. After the confirmation of the pregnancy, levothyroixine was increased to 75 μg daily and readjusted to 150 μg daily before delivery according to the monthly measurement thyroid function. Hydrocortisone 10 mg daily replaced cortisone acetate; the dose was increased according to the symptoms of morning sickness. A single stress dose of hydrocortisone (200 mg) was used before elective cesarean delivery and was tapered to the dose of 10 mg per day in 1 week. Levothyroixine was reduced to 75 μg daily after delivery. During follow-up, her hypothalamus-pituitary-adrenal (HPA) axis function was completely recovered. The peak serum cortisol level could increase to 19.08 μg/dL by insulin-induced hypoglycemia. However, growth hormone remained unresponsive to the insulin-tolerance test, and thyroid hormone still needed exogenous supplementation. Hormone replacement therapy needed closely followed by endocrinologist and multidisciplinary

Immunodetection of 11 beta-hydroxysteroid dehydrogenase type 2 in human mineralocorticoid target tissues: evidence for nuclear localization.

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Shimojo, M; Ricketts, M L; Petrelli, M D; Moradi, P; Johnson, G D; Bradwell, A R; Hewison, M; Howie, A J; Stewart, P M

1997-03-01

11 beta-Hydroxysteroid dehydrogenase (11 beta HSI) is an enzyme complex responsible for the conversion of hormonally active cortisol to inactive cortisone; two isoforms of the enzyme have been cloned and characterized. Clinical observations from patients with the hypertensive syndrome apparent mineralocorticoid excess, recently explained on the basis of mutations in the human 11 beta HSD2 gene, suggest that it is the 11 beta HSD2 isoform that serves a vital role in dictating specificity upon the mineralocorticoid receptor (MR). We have raised a novel antibody in sheep against human 11 beta HSD2 using synthetic multiantigenic peptides and have examined the localization and subcellular distribution of 11 beta HSD2 in mineralocorticoid target tissues. The immunopurified antibody recognized a single band of approximately 44 kDa in placenta, trophoblast, and distal colon. In kidney tissue, two bands of approximately 44 and 48 kDa were consistently observed. No signal was seen in decidua, adrenal, or liver. Immunoperoxidase studies on the mineralocorticoid target tissues, kidney, colon, and parotid gland indicated positive staining in epithelial cells known to express the MR: respectively, renal collecting ducts, surface and crypt colonic epithelial cells, and parotid duct epithelial cells. No staining was seen in these tissues in other sites. The intracellular localization of 11 beta HSD2 in kidney and colon epithelial cells was addressed using confocal laser microscopy. Parallel measurements of 11 beta HSD2 and nuclear propidium iodide fluorescence on sections scanned through an optical section of approximately 0.1 micron indicated significant 11 beta HSD2 immunofluorescence in the nucleus. In human kidney, colon, and salivary gland, 11 beta HSD2 protects the MR from glucocorticoid excess in an autocrine fashion. Furthermore, within these tissues, 11 beta HSD2, which had been considered to be a microsomal enzyme, is also found in the nucleus, suggesting that the

Characterization of new recombinant 3-ketosteroid-Δ1-dehydrogenases for the biotransformation of steroids.

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Wang, Xiaojun; Feng, Jinhui; Zhang, Dalong; Wu, Qiaqing; Zhu, Dunming; Ma, Yanhe

2017-08-01

3-Ketosteroid-Δ 1 -dehydrogenases (KstDs [EC 1.3.99.4]) catalyze the Δ 1 -dehydrogenation of steroids and are a class of important enzymes for steroid biotransformations. In this study, we cloned 12 putative KstD-encoding (kstd) genes from both fungal and Gram-positive microorganisms and attempted to overproduce the recombinant proteins in E. coli BL21(DE3). Five successful recombinant enzymes catalyzed the Δ 1 -desaturation of a variety of steroidal compounds such as 4-androstene-3,17-dione (AD), 9α-hydroxy-4-androstene-3,17-dione (9-OH-AD), hydrocortisone, cortisone, and cortexolone. However, the substrate specificity and catalytic efficiency of the enzymes differ depending on their sources. The purified KstD from Mycobacterium smegmatis mc 2 155 (MsKstD1) displayed high catalytic efficiency toward hydrocortisone, progesterone, and 9-OH-AD, where it had the highest affinity (K m 36.9 ± 4.6 μM) toward 9-OH-AD. On the other hand, the KstD from Rhodococcus erythropolis WY 1406 (ReKstD) exhibited high catalytic efficiency toward androst-4,9(11)-diene-3,17-dione (Diene), 21-acetoxy-pregna-4,9(11),16-triene-3,20-dione (Triene), and cortexolone, where in all three cases the K m values (12.3 to 17.8 μM) were 2.5-4-fold lower than that toward hydrocortisone (46.3 μM). For both enzymes, AD was a good substrate although ReKstD had a 3-fold higher affinity than MsKstD1. Reaction conditions were optimized for the biotransformation of AD or hydrocortisone in terms of pH, temperature, and effects of hydrogen peroxide, solvent, and electron acceptor. For the biotransformation of hydrocortisone with 20 g/L wet resting E. coli cells harboring MsKstD1 enzyme, the yield of prednisolone was about 90% within 3 h at the substrate concentration of 6 g/L, demonstrating the application potential of the newly cloned KstDs.

Activation of the baboon fetal hypothalamic-pituitary-adrenocortical axis at midgestation by estrogen-induced changes in placental corticosteroid metabolism

International Nuclear Information System (INIS)

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

1990-01-01

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

Best Practices During Hip Arthroscopy: Aggregate Recommendations of High-Volume Surgeons.

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Gupta, Asheesh; Suarez-Ahedo, Carlos; Redmond, John M; Gerhardt, Michael B; Hanypsiak, Bryan; Stake, Christine E; Finch, Nathan A; Domb, Benjamin G

2015-09-01

To survey surgeons who perform a high volume of hip arthroscopy procedures regarding their operative technique, type of procedure, and postoperative management. We conducted a cross-sectional survey of 27 high-volume orthopaedic surgeons specializing in hip arthroscopy to report their preferences and practices related to their operative practice and postoperative rehabilitation protocol. All participants completed the survey in person in an anonymous fashion during a meeting of the American Hip Institute. All surgeons perform hip arthroscopy with the patient in the supine position, accessing the central compartment of the hip initially, using intraoperative fluoroscopy. All surgeons perform labral repair (100%), with the majority performing labral reconstructions (77.8%) and gluteus medius repairs (81.5%). There is variability in the type of anchors used during labral repair. Most surgeons perform capsular closure in most cases (88.9%), inject either intra-articular cortisone or platelet-rich plasma at the conclusion of the procedure (59%), and prescribe a postoperative hip brace for some or all patients (59%). There is considerable variability in rehabilitation protocols. All surgeons routinely prescribe postoperative heterotopic ossification prophylaxis to their patients, with most surgeons (88.9%) prescribing a nonsteroidal anti-inflammatory medication for 3 weeks. Forty percent of the respondents use the modified Harris Hip Score as the most important outcome measure. Consistent practices such as use of intraoperative fluoroscopy, heterotopic ossification prophylaxis, and labral repair skills were identified by surveying 27 hip arthroscopy surgeons at high-volume centers. Most of the surgeons performed routine capsular closure unless underlying conditions precluded capsular release or plication. The survey identified higher variability between surgeons regarding postoperative rehabilitation protocols and use of intra-articular pharmacologic injections at the

2-hydroxy arachidonic acid: a new non-steroidal anti-inflammatory drug.

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Daniel H Lopez

Full Text Available BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs are a family of COX1 and COX2 inhibitors used to reduce the synthesis of pro-inflammatory mediators. In addition, inflammation often leads to a harmful generation of nitric oxide. Efforts are being done in discovering safer NSAIDs molecules capable of inhibiting the synthesis of pro-inflammatory lipid mediators and nitric oxide to reduce the side effects associated with long term therapies. METHODOLOGY/PRINCIPAL FINDINGS: The analogue of arachidonic acid (AA, 2-hydroxy-arachidonic acid (2OAA, was designed to inhibit the activities of COX1 and COX2 and it was predicted to have similar binding energies as AA for the catalytic sites of COX1 and COX2. The interaction of AA and 2OAA with COX1 and COX2 was investigated calculating the free energy of binding and the Fukui function. Toxicity was determined in mouse microglial BV-2 cells. COX1 and COX2 (PGH2 production activities were measured in vitro. COX1 and COX2 expression in human macrophage-like U937 cells were carried out by Western blot, immunocytochemistry and RT-PCR analysis. NO production (Griess method and iNOS (Western blot were determined in mouse microglial BV-2 cells. The comparative efficacy of 2OAA, ibuprofen and cortisone in lowering TNF-α serum levels was determined in C57BL6/J mice challenged with LPS. We show that the presence of the -OH group reduces the likelihood of 2OAA being subjected to H* abstraction in COX, without altering significantly the free energy of binding. The 2OAA inhibited COX1 and COX2 activities and the expression of COX2 in human U937 derived macrophages challenged with LPS. In addition, 2OAA inhibited iNOS expression and the production of NO in BV-2 microglial cells. Finally, oral administration of 2OAA decreased the plasma TNF-α levels in vivo. CONCLUSION/SIGNIFICANCE: These findings demonstrate the potential of 2OAA as a NSAID.

Impact of oral melatonin on critically ill adult patients with ICU sleep deprivation: study protocol for a randomized controlled trial.

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Huang, Huawei; Jiang, Li; Shen, Ling; Zhang, Guobin; Zhu, Bo; Cheng, Jiajia; Xi, Xiuming

2014-08-18

Sleep deprivation is common in critically ill patients in intensive care units (ICU). It can result in delirium, difficulty weaning, repeated nosocomial infections, prolonged ICU length of stay and increased ICU mortality. Melatonin, a physiological sleep regulator, is well known to benefit sleep quality in certain people, but evidence for the effectiveness in ICU sleep disturbance is limited. This study has a prospective, randomized, double-blind, controlled, parallel-group design. Eligible patients are randomly assigned to one of the two treatment study groups, labelled the 'melatonin group' or the 'placebo group'. A dose of 3 mg of oral melatonin or placebo is administered at 9:00 pm on four consecutive days. Earplugs and eye masks are made available to every participant. We plan to enrol 198 patients. The primary outcome is the objective sleep quality measured by the 24-hour polysomnography. The secondary outcomes are the subjective sleep quality assessed by the Richards Campbell Sleep Questionnaire, the anxiety level evaluated by the Visual Analogue Scale-Anxiety, the number of delirium-free days in 8 and 28 days, the number of ventilation-free days in 28 days, the number of antibiotic-free days, ICU length of stay, the overall ICU mortality in 28 days and the incidence and severity of the side effects of melatonin in ICU patients. Additionally, the body stress levels, oxidative stress levels and inflammation levels are obtained via measuring the plasma melatonin, cortisone, norepinephrine, malonaldehyde(MDA), superoxide dismutase(SOD), interleukin-6 (IL-6) and interleukin-8 (IL-8)concentrations. The proposed study will be the first randomized controlled study to use the polysomnography, which is the gold standard of assessing sleep quality, to evaluate the effect of melatonin on the sleep quality and circadian rhythms of ICU patients. The results may recommend a new treatment for ICU patients with sleep deprivation that is safe, effective and easily

The activity of 11β-hydroxysteroid dehydrogenase type 2 enzyme and cortisol secretion in patients with adrenal incidentalomas.

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Morelli, Valentina; Polledri, Elisa; Mercadante, Rosa; Zhukouskaya, Volha; Palmieri, Serena; Beck-Peccoz, Paolo; Spada, Anna; Fustinoni, Silvia; Chiodini, Iacopo

2016-09-01

In adrenal incidentaloma (AI) patients, beside the cortisol secretion, a different 11β-hydroxysteroid dehydrogenase type 2 (HSD11B2) activity, measurable by 24-h urinary cortisol/cortisone ratio (R-UFF/UFE) (the higher R-UFF/UFE the lower HSD11B2 activity), could influence the occurrence of the subclinical hypercortisolism (SH)-related complications (hypertension, type 2 diabetes, obesity). We evaluated whether in AI patients, UFF levels are associated to UFE levels, and the HSD11B2 activity to the complications presence. In 156 AI patients (93F, age 65.2 ± 9.5 years), the following were measured: serum cortisol after 1 mg-dexamethasone test (1 mg-DST), ACTH, UFF, UFE levels, and R-UFF/UFE (by liquid chromatography-tandem mass spectrometry), the latter was also evaluated in 63 matched-controls. We diagnosed SH (n = 22) in the presence of ≥2 among ACTH levels, and 1 mg-DST >83 nmol/L. Patients showed higher UFF levels and R-UFF/UFE than controls (75.9 ± 43.1 vs 54.4 ± 22.9 nmol/24 h and 0.26 ± 0.12 vs 0.20 ± 0.07, p levels (291 ± 91.1 vs 268 ± 61.5, p = 0.069). The R-UFF/UFE was higher in patients with high (h-UFF, n = 28, 0.41 ± 0.20) than in those with normal (n-UFF, 0.22 ± 0.10, p levels and in patients with SH than in those without SH (0.30 ± 0.12 vs 0.25 ± 0.12, p = 0.04). UFF levels were associated with R-UFF/UFE (r = 0.849, p levels in n-UFF patients but not in h-UFF patients, and it is not associated with the SH complications.

Resetting the Abnormal Circadian Cortisol Rhythm in Adrenal Incidentaloma Patients With Mild Autonomous Cortisol Secretion.

Science.gov (United States)

Debono, Miguel; Harrison, Robert F; Chadarevian, Rita; Gueroult, Carole; Abitbol, Jean-Louis; Newell-Price, John

2017-09-01

Adrenal incidentalomas (AIs) are found commonly on axial imaging. Around 30% exhibit autonomous cortisol secretion (ACS) associated with increased cardiovascular events and death. We hypothesized that AI/ACS patients have an abnormal cortisol rhythm that could be reversed by use of carefully timed short-acting cortisol synthesis blockade, with improvement in cardiovascular disease markers. In a phase 1/2a, prospective study (Eudract no. 2012-002586-35), we recruited six patients with AI/ACS and two control groups of six sex-, age-, and body mass index-matched individuals: (1) patients with AI and no ACS (AI/NoACS) and (2) healthy volunteers with no AI [healthy controls (HC)]. Twenty-four-hour circadian cortisol analysis was performed to determine any differences between groups and timing of intervention for cortisol lowering using the 11β-hydroxylase inhibitor metyrapone. Circadian profiles of serum interleukin-6 (IL-6) were assessed. Serum cortisol levels in group AI/ACS were significantly higher than both group AI/NoACS and group HC from 6 pm to 10 pm [area under the curve (AUC) difference: 0.81 nmol/L/h; P = 0.01] and from 10 pm to 2 am (AUC difference: 0.86 nmol/L/h; P cortisol rhythms were reassessed. Postintervention evening serum cortisol was lowered, similar to controls [6 pm to 10 pm (AUC difference: -0.06 nmol/L/h; P = 0.85); 10 pm to 2 am (AUC difference: 0.10 nmol/L/h; P = 0.76)]. Salivary cortisone showed analogous changes. IL-6 levels were elevated before treatment [10 pm to 2 pm (AUC difference: 0.42 pg/mL/h; P = 0.01)] and normalized post treatment. In AI/ACS, the evening and nocturnal cortisol exposure is increased. Use of timed evening doses of metyrapone resets the cortisol rhythm to normal. This unique treatment paradigm is associated with a reduction in the cardiovascular risk marker IL-6. Copyright © 2017 Endocrine Society

Posttherapeutic changes in bone marrow; Posttherapeutische Veraenderungen am Knochenmark

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Geith, T.; Stellwag, A.C.; Baur-Melnyk, A. [Klinikum der Universitaet Muenchen, Klinik und Poliklinik fuer Radiologie, Muenchen (Germany)

2017-11-15

The bone marrow basically consists of red blood-forming bone marrow and yellow fat. In the skeleton, there is an age-dependent distribution of these two parts. In the context of medical interventions or therapies, bone marrow changes can occur, whereby the normal bone marrow can basically be replaced by fat, edema, or fibrosis/sclerosis. Here, specific signal intensities and patterns are shown in imaging. After irradiation therapies, edematous changes, hemorrhages, and osteoradionecroses are observed. Likewise, insufficiency fractures, impairment of the growth gaps, or the development of tumors is possible. In patients on dialysis, deposit of protein in the bone marrow is possible in the case of the so-called amyloidosis osteoarthropathy. Postoperative bone marrow edema, insufficiency fractures, or osteonecrosis can be observed after arthroscopy. Changes in the distribution of fat markers and blood-forming bone marrow can be observed after stem cell transplants. In the therapy with cortisone, insufficiency fractures and osteonecroses are possible. Depending on their effect on the hematopoietic system, chemotherapies can first lead to edematous changes and then to fatty bone marrow, which is reversible after therapy. Angiogenesis inhibitors in combination with other chemotherapeutic agents often lead to mixed images of stimulated and fatty bone marrow. (orig.) [German] Das Knochenmark besteht grundsaetzlich aus rotem blutbildenden Knochenmark und gelbem Fettmark. Im Skelett besteht eine altersabhaengige Verteilung dieser beiden Anteile. Im Rahmen von aerztlichen Eingriffen oder Therapien kann es zu Veraenderungen des Knochenmarks kommen, wobei das normale Knochenmark grundsaetzlich durch Fett, Oedem oder Fibrose/Sklerose ersetzt werden kann. Dabei zeigen sich in bildgebenden Verfahren spezifische Signalintensitaeten und Muster. Nach Bestrahlungstherapien sind oedematoese Veraenderungen, Haemorrhagien und Osteoradionekrosen zu beobachten. Ebenso sind

Effects of 2G on Gene Expression of Stress-Related Hormones in Rat Placenta

Science.gov (United States)

Benson, S.; Talyansky, Y.; Moyer, E. L.; Lowe, M.; Baer, L. A.; Ronca, A. E.

2017-01-01

Understanding the effects of spaceflight on mammalian reproductive and developmental physiology is important to future human space exploration and permanent settlement beyond Earth orbit. Fetal developmental programming, including modulation of the HPA axis, is thought to originate at the placental-uterine interface, where both transfer of maternal hormones to the fetus and synthesis of endogenous hormones occurs. In healthy rats, fetal corticosterone levels are kept significantly lower by 11BetaHSD-2, which inactivates corticosterone by conversion into cortisone. Placental tissues express endogenous HPA axis-associated hormones including corticotropin-releasing hormone (CRH), pre-opiomelanocortin (POMC), and vasopressin, which may contribute to fetal programming alongside maternal hormones. DNA methylase 3A, 11BetaHSD-2, and 11BetaHSD-1, which are involved in the regulation of maternal cortisol transfer and modulation of the HPA axis, are also expressed in placental tissues along with glucocorticoid receptor and may be affected by differential gravity exposure during pregnancy. Fetuses may respond differently to maternal glucocorticoid exposure during gestation through sexually dimorphic expression of corticosterone-modulating hormones. To elucidate effects of altered gravity on placental gene expression, here we present a ground-based analogue study involving continuous centrifugation to produce 2g hypergravity. We hypothesized that exposure to 2g would induce a decrease in 11BetaHSD-2 expression through the downregulation of DNA methylase 3a and GC receptor, along with concurrent upregulation in endogenous CRH, POMC, and vasopressin expression. Timed pregnant female rats were exposed to 2G from Gestational day 6 to Gestational day 20, and comparisons made with Stationary Control (SC) and Vivarium Control (VC) dams at 1G. Dams were euthanized and placentas harvested on G20. We homogenized placental tissues, extracted and purified RNA, synthesized cDNA, and

Cost analysis of inappropriate treatments for suspected dermatomycoses

Directory of Open Access Journals (Sweden)

Emanuela Fiammenghi

2015-06-01

Full Text Available Superficial mycoses are estimated to affect more than 20-25% of the world’s population with a consistent increase over the years. Most patients referred to our clinic for suspected dermatomycoses have already been treated with pharmacotherapy, without a previous mycological examination and many show changes in the clinical manifestations. Indeed, some medications, such as steroids, antiviral, antibiotics and antihistamines are not able to erase a fungal infection, but also they can cause atypical clinical manifestations. The consequences of inappropriate treatment include delayed diagnosis, prolonged healing time, and additional costs. The aims of this study were (1 to evaluate the incidence of increased costs attributable to inappropriate therapy sustained by the National Health Service and patients and (2 to highlight the importance of mycological evaluation before starting treatment, in order to improve diagnostic accuracy. An observational retrospective and prospective study was performed from September 2013 to February 2014, in 765 patients referred to our center (University Hospital “ Federico II” in Naples, Italy, for suspected mycological infection. The following treatments (alone or in combination were defined as inappropriate: (1 cortisone in a patient with at least one positive site; (2 antifungals in (a patients with all negative sites or (b ineffective antifungal treatment (in terms of drug chosen, dose or duration in those with all positive sites; or (3 antibiotics; (4 antivirals or (5 antihistamines, in patients with ≥ 1 positive site. Five hundred and fifty patients were using medications before the assessment visit. The total amount of avoidable costs related to inappropriate previous treatments was € 121,417, representing 74% of the total treatment costs. 253/550 patients received drugs also after the visit. For these patients, the cost of treatment prescribed after mycological testing was € 42,952, with a decrease

Effects and Complications of Bone-Marrow Transplantation in Man

Energy Technology Data Exchange (ETDEWEB)

Mathe, G.; Schwarzenberg, L.; Miel, J.L. A; Schneider, M.; Cattan, A.; Schlumberger, J. R. [Institut de cancerologie et immunogenetique, Hopital Paul Brousse, Villejuif (France)

1969-07-15

Full text: Allogenic bone-marrow grafting in 24 human leukaemic subjects is described. The graft failed in 7 cases and took in 17 cases. In the latter group, all 17 cases were complicated by the secondary syndrome which was-fatal in 13 cases and controlled in 4 cases. The immunogenetic and immunological factors determining the establishment and evolution of haematological radiochimeras in man are discussed. The choice of donor is fundamental. Three tests are effective in donor selection, the indirect histocompatibility test, the leucocyte antigen test and the reaction of donor and recipient leucocytes in the dermis of an irradiated hamster. When marrow from several donors is transfused, the recipient spontaneously selects the genetically nearest. It seems likely there is more chance of finding a suitable donor among genetically related subjects than among those who are unrelated. The frequency of graft take seems slightly lower in recipients who have previously received blood transfusions. Total bone-marrow graft is associated with specific tolerance towards donor tissues. This is paralleled by the production in the chimera of immunoglobulins produced by the graft. The secondary syndrome seems, as in animals, to be related essentially to the graft-versus-host reaction. It is convenient to distinguish among its various manifestations, on the one hand, those lesions which are readily controlled such as hepatitis or erythrodermia associated with infiltration and proliferation of immunologically competent cells from the graft and, on the other hand, immune insufficiency with regard to micro-organisms, especially viruses and Candida albicans. This latter group, the mechanism of which is complex, still eludes attempts at preventive and curative control. The use of multiple donors and the administration of cortisone during marrow transfusion and A-methopterin and/or cyclophosphamide in the days following transfusions; seem to have reduced the severity of the secondary

Longitudinal measurement of cortisol in association with mental health and experience of domestic violence and abuse: study protocol.

Science.gov (United States)

Lokhmatkina, Natalia V; Feder, Gene; Blake, Sarah; Morris, Richard; Powers, Victoria; Lightman, Stafford

2013-07-13

Domestic violence and abuse is threatening behavior, violence/abuse used by one person to control the other within an intimate or family-type relationship. Women experience more severe physical and sexual domestic violence and abuse and more mental health consequences than men. The current study aims at exploring of the role of hypothalamic-pituitary-adrenocortical axis activity in abuse impact on women's mental health. 1) To evaluate diurnal cortisol slope, cortisol awakening response, and the mean cortisol concentration in women with a current or recent experience of abuse; 2) To estimate whether cortisol secretion is associated with type, severity, duration and cessation of abuse; 3) To investigate whether cortisol acts as mediator between abuse and mental health condition; 4) To examine whether there is any distinction in cortisol levels between those women exposed to both childhood abuse and domestic violence and abuse and those experienced only the latter. 4) To explore whether cortisol secretion differs between women living in refuge and those still living in the community. To meet study objectives 128 women will be recruited in a domestic violence agency and local communities. Baseline and 3-month follow-up measures will be taken over 6 months after recruitment. Each assessment will include: (1) standardized self-administered questionnaires to evaluate socio-demographics, experience of violence and abuse, mental and physical health; (2) weight and height measurement; (3) self-completion of wakening, post-wakening and evening saliva samples. Saliva will be analysed for cortisol and cortisone using Ultra performance liquid chromatography-tandem mass spectrometry. We will compare diurnal cortisol parameters between non-abused controls and abuse survivors with and without mental health conditions. First following descriptive statistics for all the cortisol and mental health outcomes, relationships between them will be investigated using appropriate regression

11β-Hydroxysteroid dehydrogenase 1 contributes to the pro-inflammatory response of keratinocytes

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Itoi, Saori; Terao, Mika, E-mail: mterao@derma.med.osaka-u.ac.jp; Murota, Hiroyuki; Katayama, Ichiro

2013-10-18

Highlights: •We investigate the role of 11β-HSD1 in skin inflammation. •Various stimuli increase expression of 11β-HSD1 in keratinocytes. •11β-HSD1 knockdown by siRNA decreases cortisol levels in media. •11β-HSD1 knockdown abrogates the response to pro-inflammatory cytokines. •Low-dose versus high-dose cortisol has opposing effects on keratinocyte inflammation. -- Abstract: 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{sup −13} M cortisol, whereas 1 × 10{sup −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

11β-Hydroxysteroid dehydrogenase 1 contributes to the pro-inflammatory response of keratinocytes

International Nuclear Information System (INIS)

Itoi, Saori; Terao, Mika; Murota, Hiroyuki; Katayama, Ichiro

2013-01-01

Highlights: •We investigate the role of 11β-HSD1 in skin inflammation. •Various stimuli increase expression of 11β-HSD1 in keratinocytes. •11β-HSD1 knockdown by siRNA decreases cortisol levels in media. •11β-HSD1 knockdown abrogates the response to pro-inflammatory cytokines. •Low-dose versus high-dose cortisol has opposing effects on keratinocyte inflammation. -- Abstract: 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

Impact of HSD11B1 polymorphisms on BMI and components of the metabolic syndrome in patients receiving psychotropic treatments

KAUST Repository

Quteineh, Lina; Vandenberghe, Frederik; Saigi Morgui, Nuria; Delacré taz, Auré lie; Choong, Eva; Gholam-Rezaee, Mehdi; Magistretti, Pierre J.; Bondolfi, Guido; Von Gunten, Armin; Preisig, Martin A.; Castelao, Enrique; Vollenweider, Peter; Waeber, Gé rard; Bochud, Murielle; Kutalik, Zoltá n; Conus, Philippe O.; Eap, Chin Bin

2015-01-01

Background Metabolic syndrome (MetS) associated with psychiatric disorders and psychotropic treatments represents a major health issue. 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) is an enzyme that catalyzes tissue regeneration of active cortisol from cortisone. Elevated enzymatic activity of 11β-HSD1 may lead to the development of MetS. Methods We investigated the association between seven HSD11B1 gene (encoding 11β-HSD1) polymorphisms and BMI and MetS components in a psychiatric sample treated with potential weight gain-inducing psychotropic drugs (n=478). The polymorphisms that survived Bonferroni correction were analyzed in two independent psychiatric samples (n R1 =168, n R2 =188) and in several large population-based samples (n 1 =5338; n 2 =123 865; n 3 >100 000). Results HSD11B1 rs846910-A, rs375319-A, and rs4844488-G allele carriers were found to be associated with lower BMI, waist circumference, and diastolic blood pressure compared with the reference genotype (P corrected <0.05). These associations were exclusively detected in women (n=257) with more than 3.1 kg/m 2, 7.5 cm, and 4.2 mmHg lower BMI, waist circumference, and diastolic blood pressure, respectively, in rs846910-A, rs375319-A, and rs4844488-G allele carriers compared with noncarriers (P corrected <0.05). Conversely, carriers of the rs846906-T allele had significantly higher waist circumference and triglycerides and lower high-density lipoprotein-cholesterol exclusively in men (P corrected =0.028). The rs846906-T allele was also associated with a higher risk of MetS at 3 months of follow-up (odds ratio: 3.31, 95% confidence interval: 1.53-7.17, P corrected =0.014). No association was observed between HSD11B1 polymorphisms and BMI and MetS components in the population-based samples. Conclusions Our results indicate that HSD11B1 polymorphisms may contribute toward the development of MetS in psychiatric patients treated with potential weight gain-inducing psychotropic drugs, but do not

11-Hydroxy-β-steroid dehydrogenase gene expression in canine adipose tissue and adipocytes: stimulation by lipopolysaccharide and tumor necrosis factor α.

Science.gov (United States)

Ryan, V H; Trayhurn, P; Hunter, L; Morris, P J; German, A J

2011-10-01

The enzyme 11β-hydroxysteroid dehydrogenase 1 (11β-HSD-1) is expressed in a number of tissues in rodents and humans and is responsible for the reactivation of inert cortisone into cortisol. Its gene expression and activity are increased in white adipose tissue (WAT) from obese humans and may contribute to the adverse metabolic consequences of obesity and the metabolic syndrome. The extent to which 11β-HSD-1 contributes to adipose tissue function in dogs is unknown; the aim of the present study was to examine 11β-HSD-1 gene expression and its regulation by proinflammatory and anti-inflammatory agents in canine adipocytes. Real-time PCR was used to examine the expression of 11β-HSD-1 in canine adipose tissue and canine adipocytes differentiated in culture. The mRNA encoding 11β-HSD-1 was identified in all the major WAT depots in dogs and also in liver, kidney, and spleen. Quantification by real-time PCR showed that 11β-HSD-1 mRNA was least in perirenal and falciform depots and greatest in subcutaneous, omental, and gonadal depots. Greater expression was seen in the omental depot in female than in male dogs (P=0.05). Gene expression for 11β-HSD-1 was also seen in adipocytes, from both subcutaneous and visceral depots, differentiated in culture; expression was evident throughout differentiation but was generally greatest in preadipocytes and during early differentiation, declining as cells progressed to maturity. The inflammatory mediators lipopolysaccharide and tumor necrosis factor α had a main stimulatory effect on 11β-HSD-1 gene expression in canine subcutaneous adipocytes, but IL-6 had no significant effect. Treatment with dexamethasone resulted in a significant time- and dose-dependent increase in 11β-HSD-1 gene expression, with greatest effects seen at 24 h (2 nM: approximately 4-fold; 20 nM: approximately 14-fold; P=0.010 for both). When subcutaneous adipocytes were treated with the peroxisome proliferator activated receptor γ agonist rosiglitazone

Radioiodine treatment of Grave's disease; Radiojodtherapie des Morbus Basedow

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Heidenreich, P.; Vogt, H.; Dorn, R.; Graf, G.; Kopp, J. [Klinik fuer Nuklearmedizin, Zentralklinikum Augsburg (Germany)

2001-09-01

In Germany radioiodine therapy of Grave's disease is performed in patients older than 20 years, after at least one year of unsuccessful antithyroid therapy, intolerance against antithyroid medication, recurrences after surgical interventions and small goiters. Hyperthyroidism is eliminated with an ablative dose concept (300 Gy) in more than 90% associated with rate of hypothyroidism in the outcome of also more than 90%. Adverse prognostic factors are an insufficient dose to the thyroid and/or concomitant antithyreoid medication. Radioiodine therapy in Germany must be an inpatient single time approach due to quality assurance and radiation protection reasons. The mean hospitalization is only 3-4 days with the patient being discharged at an annual dose of less than 1 mSv at 2 m distance (dose rate at discharge < 3,5 {mu}Sv/h at 2 m). An adjuvant treatment with cortisone is recommended in a simultaneous endocrine ophthalmopathy to prevent from deterioration. Radioiodine therapy of Grave's disease is cost effective with a low probability of side-effects and is not associated with an increased genetic or somatic risk. Therapy control and life span follow up has to be carried out by the expert physician legally responsible for the radioiodine therapy. (orig.) [German] Die Radiojodtherapie des Morbus Basedow wird in Deutschland, bei Patienten aelter als 20 Jahre, erst nach mindestens einjaehriger, erfolgloser thyreostatischer Therapie, bei Thyreostatikaunvertraeglichkeit, Rezidiven nach Operation und kleinen Strumen durchgefuehrt. Die Beseitigung der Hyperthyreose wird mit einem ablativen Dosiskonzept (300 Gy) in > 90%, verbunden mit einer Hypothyreoserate von ebenfalls > 90% erreicht. Prognostisch unguenstige Einflussfaktoren sind eine zu niedrig gewaehlte Herddosis und/oder eine begleitende Thyreostase. Aus Gruenden der Qualitaetssicherung und des Strahlenschutzes muss in Deutschland die Radiojodtherapie stationaer als Einzeittherapie durchgefuehrt werden. Die

Diseño y evaluación de nuevas formulaciones de tabletas de acetato de cortisona (25 mg

Directory of Open Access Journals (Sweden)

Lissette González Chávez

2002-04-01

Full Text Available Se produjeron 3 formulaciones diferentes de tabletas de acetato de cortisona (25 mg a escala de laboratorio, con el objetivo de obtener una formulación que cumpla con los parámetros establecidos en la Farmacopea Británica (2000, específicamente el parámetro de disolución con el cual no cumple la formulación actual. En las 3 formulaciones estudiadas se sustituyó la solución aglutinante de la formulación actual (gelatina-almidón por la polivinilpirrolidona en solución alcohólica y se adicionó desintegrante extragranular (acdisol, entre otras variaciones. Las tabletas se analizaron teniendo en cuenta las características tecnológicas y analíticas según las especificaciones de calidad de las farmacopeas oficiales; se realizaron además el ensayo de uniformidad de contenido, con el empleo de un método espectrofotométrico previamente validado. Se estudió la estabilidad física y química de las 3 formulaciones ensayadas por un período de 3 a. Todas las formulaciones cumplieron con los parámetros de calidad establecidos, recién fabricadas y durante el período de vida útil estudiado, lo cual soporta la factibilidad para su producción a escala piloto.Three different formulations of cortisone acetate tablets (25 mg were produced at laboratory scale aimed at obtaining a formulation that fulfills the parameters established by the British Pharmacopoeia (2000, specifically the dissolution parameter that is not fulfilled by the current formulation. In the 3 studied formulations the agglutinant solution of the present formulation (gelatin-starch was substituted by polyvynilpyrrolidone in alcoholic solution and extragranular disintegrator (acdisol was added, among other variations. The tablets were analyzed taking into account the technological and analytical characteristics according to the quality specifications of the official pharmacopoeias. The content uniformity trial was also carried out by using a spectrophotometric method

Battling the hematological malignancies: the 200 years' war.

Science.gov (United States)

Lichtman, Marshall A

2008-02-01

The delineation of the hematological malignancies began near the end of the first third of the 19th century with the recognition of the similarity among cases with lymph node tumors and an enlarged spleen (Hodgkin's disease). Descriptions of chronic and acute leukemia and myeloma followed thereafter. In the first years of the 20th century the discovery of x-radiation permitted palliative orthovoltage radiation therapy of Hodgkin's disease. Following World War II, legitimate drug therapy for the hematological malignancies was introduced: nitrogen mustard, adrenocorticotropic hormone and cortisone acetate, and anti-folic acid derivatives, initially aminopterin. Today, about 14 classes of drugs (different mechanisms of action) and >50 individual agents are being used, with others under study. Several examples of agents targeting specific transcription factors or oncoproteins have been introduced. Despite remarkable progress, including the ability to cure acute leukemia in about 70% of children, cure several genetic variants of acute myelogenous leukemia in younger adults, cure some cases of lymphoma in children and younger adults, and induce prolonged remission in many affected persons, the majority of patients face an uncertain outcome and shortened life. Thus, we have much to do in the next several decades. The significant hurdles we must overcome include: the apparent infrequency of an exogenous cause that can be avoided, the exponential increase in incidence rates with age and the dramatic negative effect of aging on the results of treatment, the challenge of one trillion or more disseminated cancer cells among which are a smaller population of cancer stem cells, the profound genetic diversity of the hematological malignancies (apparently hundreds of unique genetic primary lesions), the redundant growth and survival pathways defining the cancer phenotype, the decreasing market for pharmaceutical companies as therapy becomes more specific (fewer target patients

Altered placental development in undernourished rats: role of maternal glucocorticoids

Directory of Open Access Journals (Sweden)

Chen Chun-Hung

2011-08-01

Full Text Available Abstract Maternal undernutrition (MUN during pregnancy may lead to fetal intrauterine growth restriction (IUGR, which itself predisposes to adult risk of obesity, hypertension, and diabetes. IUGR may stem from insufficient maternal nutrient supply or reduced placental nutrient transfer. In addition, a critical role for maternal stress-induced glucocorticoids (GCs has been suggested to contribute to both IUGR and the ensuing risk of adult metabolic syndrome. While GC-induced fetal organ defects have been examined, there have been few studies on placental responses to MUN-induced maternal stress. Therefore, we hypothesize that 50% MUN associates with increased maternal GC levels and decreased placental HSD11B. This in turn leads to decreased placental and fetal growth, hence the need to investigate nutrient transporters. We measured maternal serum levels of corticosterone, and the placental basal and labyrinth zone expression of glucocorticoid receptor (NR3C1, 11-hydroxysteroid dehydrogenase B 1 (HSD11B-1 predominantly activates cortisone to cortisol and 11-dehydrocorticosterone (11-DHC to corticosterone, although can sometimes drive the opposing (inactivating reaction, and HSD11B-2 (only inactivates and converts corticosterone to 11-DHC in rodents in control and MUN rats at embryonic day 20 (E20. Moreover, we evaluated the expression of nutrient transporters for glucose (SLC2A1, SLC2A3 and amino acids (SLC38A1, 2, and 4. Our results show that MUN dams displayed significantly increased plasma corticosterone levels compared to control dams. Further, a reduction in fetal and placental weights was observed in both the mid-horn and proximal-horn positions. Notably, the placental labyrinth zone, the site of feto-maternal exchange, showed decreased expression of HSD11B1-2 in both horns, and increased HSD11B-1 in proximal-horn placentas, but no change in NR3C1. The reduced placental GCs catabolic capacity was accompanied by downregulation of SLC2A3, SLC

Urethane influence in the urine formation in swiss rats and syrian hamster

International Nuclear Information System (INIS)

Lima, Marina F.; Silva, Natanael G.; Mesquita, Carlos Henrique de

2011-01-01

Urethane is an anaesthetic agent with minimal cardiovascular and respiratory system depression with long-lasting (6-10h) effects. Its carcinogenic potential avoids it from veterinary use. Either, the knowledge of its effects over the circulating catecholamines (cortisone and corticosterone), with reflects in the muscles physiology, it is widely used in pharmacological studies in laboratory species. At the first minutes, Urethane induces a hyperglycaemia condition due the insulin concentration decrease, later than, the insulin concentration and the condition becomes in hypoglycaemia, but the Urethane interfering in the urine production mechanisms has not been described. It is accepted that the glycolic level would not interferes in the kidney function, except in chronic states, notably associated with insulin related diseases. The relative high biological half-life of 177 Lu-Dotatate allows its use in biodistribution studies among small animals whose metabolic rates are so fast that would be impossible observe them with the most part of the labeled molecules. During the performance of a cross-species extrapolation study using Urethane as anaesthesia and 177 Lu-Dotatate as metabolic tracer, was observed the Urethane influence over urine formation in Swiss rats and Syrian hamster (Mesocricetus auratus). The objective of this work is only describes the Urethane action over the urine production. Firstly, four male inbread Wistar Swiss rats (±250 g), are anesthetized, with around 1200 mg/kg, i.p., in groups of two. One rat from each group get ahead to the injection of 177 Lu-Dotatate and Gamma camera in vivo study, the second ones, anesthetized, waited under warming lights until more than one hour to initiate the biodistribution study. The scintillographical images shown the radiopeptide stopped at the kidneys and the urinary empty in the animals who attempt more than one hour before enter to radiopharmaceutical injection and Gamma camera imaging procedures. The rates

Urethane influence in the urine formation in swiss rats and syrian hamster

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Lima, Marina F.; Silva, Natanael G.; Mesquita, Carlos Henrique de, E-mail: mflima@ipen.br, E-mail: ngsilva@ipen.br, E-mail: chmesqui@ipen.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

2011-07-01

Urethane is an anaesthetic agent with minimal cardiovascular and respiratory system depression with long-lasting (6-10h) effects. Its carcinogenic potential avoids it from veterinary use. Either, the knowledge of its effects over the circulating catecholamines (cortisone and corticosterone), with reflects in the muscles physiology, it is widely used in pharmacological studies in laboratory species. At the first minutes, Urethane induces a hyperglycaemia condition due the insulin concentration decrease, later than, the insulin concentration and the condition becomes in hypoglycaemia, but the Urethane interfering in the urine production mechanisms has not been described. It is accepted that the glycolic level would not interferes in the kidney function, except in chronic states, notably associated with insulin related diseases. The relative high biological half-life of {sup 177}Lu-Dotatate allows its use in biodistribution studies among small animals whose metabolic rates are so fast that would be impossible observe them with the most part of the labeled molecules. During the performance of a cross-species extrapolation study using Urethane as anaesthesia and {sup 177}Lu-Dotatate as metabolic tracer, was observed the Urethane influence over urine formation in Swiss rats and Syrian hamster (Mesocricetus auratus). The objective of this work is only describes the Urethane action over the urine production. Firstly, four male inbread Wistar Swiss rats ({+-}250 g), are anesthetized, with around 1200 mg/kg, i.p., in groups of two. One rat from each group get ahead to the injection of {sup 177}Lu-Dotatate and Gamma camera in vivo study, the second ones, anesthetized, waited under warming lights until more than one hour to initiate the biodistribution study. The scintillographical images shown the radiopeptide stopped at the kidneys and the urinary empty in the animals who attempt more than one hour before enter to radiopharmaceutical injection and Gamma camera imaging

Anti-inflammatory treatment for carditis in acute rheumatic fever.

Science.gov (United States)

Cilliers, Antoinette; Adler, Alma J; Saloojee, Haroon

2015-05-28

Rheumatic heart disease remains an important cause of acquired heart disease in developing countries. Although prevention of rheumatic fever and management of recurrences have been well established, optimal management of active rheumatic carditis remains unclear. This is an update of a review published in 2003, and previously updated in 2009 and 2012. To assess the effects, both harmful and beneficial, of anti-inflammatory agents such as aspirin, corticosteroids and other drugs in preventing or reducing further valvular damage in patients with acute rheumatic fever. We searched the Cochrane Central Register of Controlled Trials (2013, Issue 9 of 12), MEDLINE (Ovid, 1948 to 2013 October Week 1), EMBASE (Ovid, 1980 to 2013 Week 41) and Latin American Caribbean Health Sciences Literature (LILACS) (1982 to 17 October 2013). We last searched Index Medicus (1950 to April 2001) in 2001. We checked reference lists of identified studies and applied no language restrictions. Randomised controlled trials comparing anti-inflammatory agents (e.g. aspirin, steroids, immunoglobulins, pentoxifylline) versus placebo or controls, or comparing any of the anti-inflammatory agents versus one another, in adults and children with acute rheumatic fever diagnosed according to Jones, or modified Jones, criteria. The presence of cardiac disease one year after treatment was the major outcome criterion selected. Two review authors extracted data and assessed risk of bias using the methodology outlined in the Cochrane Handbook of Systematic Reviews of Interventions. Standard methodological procedures as expected by The Cochrane Collaboration were used. No new studies were included in this update. Eight randomised controlled trials involving 996 people were selected for inclusion in the review. Researchers compared several steroidal agents such as corticotrophin, cortisone, hydrocortisone, dexamethasone, prednisone and intravenous immunoglobulin versus aspirin, placebo or no treatment. Six

IL-6 anti-inflammatory activity in pleural effusion post-coronary artery bypass graft surgery

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António M S Chibante

2007-05-01

Full Text Available Introduction: The local inflammatory reaction aspects of pleural behaviour post-coronary artery bypass graft surgery (PCABG are not completely evident, demanding further study and observation. Aim: To evaluate the behaviour of some cytokines and the possible anti-inflammatory activity of IL-6 (a protein involved in cortisone synthesis on acute PCABG pleural fluid, since this cytokine is usually considered as an acute phase reaction protein associated to high concentrations of TNF-alpha and IL-1beta in immediate inflammatory reactions. Material and methods: The concentrations of the TNFalpha, IL-1beta, IL-2, IL-6, IL-8, VEGF and TGF-beta cytokines in 16 transudates and 43 exudates in acute PCABS pleural fluid of patients were analysed by the ELISA method 2, 24 and 48 hours after surgery at the Instituto do Coração and Serviço de Pneumologia da USP, Brazil. Results: While no increase was seen in either TNF-alpha or IL-2 in any of the three tests, IL-1beta increased after 24 until 48 hours, coinciding with the TGF-beta curve decline which fell from the beginning to reach the transudates levels. IL-8 reminded higher from the beginning and through the two subsequent tests while VEGF levels were elevated from the first test and continued high for the following 24 and 48 hours. IL-6 had high concentrations from the beginning, suggesting an anti-inflammatory activity at the three times of testing. Conclusions: We conclude that IL-6 seems to play an important anti-inflammatory part which is superior to the anti-inflammatory activity of TGF-beta in PCABG pleural effusions. This performance of IL-6 breaks with the traditional idea of it being a pro-inflammatory acute phase reaction cytokine, at least in this type of pleural effusion. This seems to be the first study involving the favourable behaviour of IL-6 in the inflammatory reaction of pleura in the acute phase of PCABG surgery. Resumo: Introdução: O comportamento pleural p

Comportamento anti-inflamatório da IL-6 nos derrames pleurais pós-revascularização do miocárdio*

Directory of Open Access Journals (Sweden)

António M.S. Chibante

2007-05-01

ó-inflamatória de resposta de fase aguda. Ao que parece, este é o primeiro estudo que procura demonstrar um papel favorável da IL-6 no processo inflamatório da pleura na fase aguda PCRM.Rev Port Pneumol 2007; XIII (3: 319-334 Abstract: Introduction: The local inflammatory reaction as-pects of pleural behaviour post-coronary artery bypass graft surgery (PCABG are not completely evident, demanding further study and observation.Aim: To evaluate the behaviour of some cytokines and the possible anti-inflammatory activity of IL-6 (a protein involved in cortisone synthesis on acute PCABG pleural fluid, since this cytokine is usually considered as an acute phase reaction protein associated to high concentrations of TNF-alpha and IL-1beta in immediate inflammatory reactions.Material and methods: The concentrations of the TNF-alpha, IL-1beta, IL-2, IL-6, IL-8, VEGF and TGF-beta cytokines in 16 transudates and 43 exudates in acute PCABS pleural fluid of patients were analysed by the ELISA method 2, 24 and 48 hours after surgery at the Instituto do Coração and Serviço de Pneumologia da USP, Brazil.Results: While no increase was seen in either TNF-alpha or IL-2 in any of the three tests, IL-1beta increased after 24 until 48 hours, coinciding with the TGF-beta curve decline which fell from the beginning to reach the transudates levels. IL-8 reminded higher from the beginning and through the two subsequent tests while VEGF levels were elevated from the first test and continued high for the following 24 and 48 hours. IL-6 had high concentrations from the beginning, suggesting an anti-inflammatory activity at the three times of testing.Conclusions: We conclude that IL-6 seems to play an important anti-inflammatory part which is superior to the anti-inflammatory activity of TGF-beta in PCABG pleural effusions. This performance of IL-6 breaks with the traditional idea of it being a pro-in-flammatory acute phase reaction cytokine, at least in this type of pleural effusion. This seems

Applications of Fluorine-18 in Biological Studies with Special Reference to Bone and Thyroid Physiology; Emploi du Fluor-18 dans des Études Biologiques, Notamment sur la Physiologie des Os et de la Thyroïde; ИСПОЛЬЗОВАНИЕ ФТОРА-18 В БИОЛОГИЧЕСКИХ ИССЛЕДОВАНИЯХ С УДЕЛЕНИЕМ ОСОБОГО ВНИМАНИЯ ВОПРОСАМ ФИЗИОЛОГИИ КОСТЕЙ И ФИЗИОЛОГИИ ПИТОВИДНОЙ ЖЕЛЕЗЫ; Aplicaciones del Fluor-18 en Estudios Biologicos, con Especial Referencia a la Fisiologia del Esqueleto y de la Tiroides

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Anbar, M. [Weizmann Institute of Science (Israel); IAEC Soreq Research Establishment, Rehovot (Israel)

1963-03-15

the trapping of fluoroborate, although they diminish the overall iodine uptake. Next, it was demonstrated that the trapping stage is much less radiosensitive than the stages of thyroxine formation and release. A quite different application of F{sup 16}-labelled fluoroborate ions was in the localization of brain tumours, by directional coincidence scanning owing to the limited permeability of these ions via the intact blood- brain barrier. Fluorine-18 labelled fluoraromatic chelating agents were prepared and applied to problems in bone physiology. Fluorine-18 labelled aromatic vital dyes were used in investigating problems of permeability through biological membranes. Fluorine-18 labelled fluorine containing antimetabolites including 5-fluorouracyl and fluoro-orotic acid, have been prepared and applied to physiological problems, including cancer research. (author) [French] Dans les laboratoires de la CEAI, le fluor-18 a ete utilise au cours des trois dernieres annees pour resoudre de nombreux problemes de biologie et de medecine. Des methodes ont ete mises au point pour preparer le fluor par chacune des reactions {sup 18}O (p, n), {sup 16}O(H{sup 3}, n) et {sup 18}F(n, 2n). Des composes marques au radiofluor ont ete prepares par echange isotopique, synthese, marquage par recul et retention du fluor dans des composes fluores organiques soumis a la reaction (n, 2n). Des techniques speciales de comptage ont ete mises au point pour mesurer les faibles activites de doses traceuses de composes fluores organiques. Les ions {sup 18}F{sup -} ont ete utilises pour des etudes sur la physiologie des os. On a constate que l'ion F' est semblable au calcium en de nombreux aspects de son comportement physiologique; on a observe que la fixation F par l'os augmente sous l'influence de la vitamine D et de la testosterone tandis que la cortisone et les oestrogenes reduisent le taux de fixation. Le mode de distribution du fluor dans l'organisme se modifie lorsqu'il est administre sous la