11ß-hydroxysteroid dehydrogenase type-II activity is affected by grapefruit juice and intense muscular work

ABSTRACT Objective The enzymatic activity of 11β-hydroxysteroid dehydrogenase-2 (11β-HSD2) is key to protecting mineral corticoid receptors from cortisol and has been implicated in blood pressure regulation. Grapefruit juice (GFJ) and acidity are thought to inhibit this enzyme in vitro. This study examines the effect of GFJ and intense exercise on 11β-HSD2 enzyme activity in vivo. Subjects and methods Eighteen subjects ingested GFJ or apple juice (CON) on separate days prior to reporting to the laboratory in a randomized order. Saliva (Sal) samples were obtained at baseline, 15 and 45 minutes post-treadmill stress test; Sal cortisone (E) and cortisol (F) levels were determined, and the Sal cortisone:cortisol (E:F) ratio was used as an index of 11β-HSD2 enzyme activity at rest and after intense muscular work. Results GFJ treatment decreased baseline 11β-HSD2 enzyme activity (44%) and Sal-E (28%) compared to CON (both, p < 0.05). Sal-E (r = 0.61, p < 0.05) and Sal-F (r = 0.66, p < 0.05) were correlated with diastolic blood pressure (DBP) in GFJ-treated individuals. Treadmill stress significantly increased Sal-E and Sal-F but did not alter 11β-HSD2 enzyme activity regardless of treatment. When treatments were examined separately, CON 11β-HSD2 enzyme activity decreased by 36% (p < 0.05) from baseline to 15 post-treadmill exercise. Conclusion Our findings suggest that GFJ and intense muscular work decrease 11β-HSD-2 activity independently, and no additive effect was noted. The association between DBP and the levels of Sal-F and Sal-E during the GFJ trial should be interpreted cautiously and warrants further investigation.

Effects of Music Therapy on Subjective Stress Response, Salivary Cortisol, and Fatigue for Intensive Care Nurses

BACKGROUND: The purpose of this study was to verify the effects of music therapy on subjective stress response, salivary cortisol and fatigue for nurses working in intensive care unit (ICU). METHODS: This study employed non-equivalent control group pretest–posttest design on quasi experimental basis. Subjects were 52 nurses (26 experimental and control group respectively) who have been working at ICU of Gil Hospital in Incheon, Korea. Data were collected from August 4 to October 6, 2014. Experimental group have listened to their 4-7 favorite musics individually once for 30 minutes after day-work. RESULTS: In experimental group, subjective stress response (t=5.02, P<0.001), salivary cortisol (t=2.08, P=0.042), and fatigue (t=5.66, P<0.001) have decreased significantly comparing to the control group. CONCLUSIONS: This study has confirmed especially through objective physiological index of salivary cortisol that listening the favorite music for nurses in ICU was an effective and objective managerial measure to resolve their job stress and fatigue.

Effects of Cellular 11β-hydroxysteroid Dehydrogenase 1 on LPS-induced Inflammatory Responses in Synovial Cell Line, SW982

11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) catalyzes the conversion of inactive cortisone into active cortisol, which has pleiotropic roles in various biological conditions, such as immunological and metabolic homeostasis. Cortisol is mainly produced in the adrenal gland, but can be locally regenerated in the liver, fat, and muscle. Its diverse actions are primarily mediated by binding to the glucocorticoid receptor. SW982, a human synovial cell line, expresses 11β-HSD type 1, but not type 2, that catalyzes the conversion of cortisone to cortisol. In this study, therefore, we investigated the control of lipopolysaccharide (LPS)-induced inflammatory responses by prereceptor regulation-mediated maintenance of cortisol levels. Preliminarily, cell seeding density and incubation period were optimized for analyzing the catalytic activity of SW982. Additionally, cellular 11β-HSD1 still remained active irrespective of monolayer or spheroid culture conditions. Inflammatory stimulants, such as interleukin (IL)-1β, tumor necrosis factor (TNF)α, and LPS, did not affect the catalytic activity of 11β-HSD1, although a high dose of LPS significantly decreased its activity. Additionally, autocrine effects of cortisol on inflammatory responses were investigated in LPS-stimulated SW982 cells. LPS upregulated pro-inflammatory cytokines, including IL-6 and IL-1β, in SW982 cells, while cortisol production, catalyzed by cellular 11β-HSD1, downregulated LPS-stimulated cytokines. Furthermore, suppression of NFκB activation-mediated pro-inflammatory responses by cortisol was revealed. In conclusion, the activity of cellular 11β-HSD1 was closely correlated with suppression of LPS-induced inflammation. Therefore, these results partly support the notion that prereceptor regulation of locally regenerated cortisol could be taken into consideration for treatment of inflammation-associated diseases, including arthritis.

Simultaneous Determination of Tetracycline Hydrochloride and Cortisone Acetate in Cortisone Tetracycline Eye Ointment by HPLC / 中国药房

OBJECTIVE:To establish a method for the simultaneous determination of tetracycline hydrochloride and cortisone acetate in Cortisone tetracycline eye ointment. METHODS:HPLC was performed on the column of Phenomenex C18 and shimaduz GL C18 with mobile phase of 0.01 mol/L Sodium dodecyl sulfate solution(adjusted to pH 2.5 with phosphoric acid)-acetonitrile(60∶40,V/V)at flow rate of 1.0 ml/min,detection wavelength was 254 nm,column temperature was 30 ℃,and the injection volume was 20 μl. RESULTS:The linear range was 11.36-227.18 μg/ml for tetracycline hydrochloride(r=0.999 9)and 11.11-222.21 μg/ml for cortisone acetate(r=0.999 9);RSDs of precision,stability and reproducibility tests were no more than 1.2%;recoveries were 96.89%-100.67%(RSD=1.1%,n=9)and 100.04%-101.02%(RSD=0.3%,n=9),respectively. CONCLUSIONS:The method is simple,accurate and specific,and can accurately determine the contents of tetracycline hydrochloride and cortisone acetate in Corti-sone tetracycline eye ointment.

Effects of Foot-Reflexology Massage on Fatigue, Stress and Postpartum Depression in Postpartum Women

PURPOSE: To identify the effects of foot reflexology massage on fatigue, stress and depression of postpartum women. METHODS: A nonequivalent control group pre-post design was used. A total of 70 women in a postpartum care center were recruited and were assigned to the experimental group (35) or control group (35). Foot reflexology massage was provided to the experimental group once a day for three days. Data were collected before and after the intervention program which was carried out from December, 2013 to February, 2014. Data were analyzed using Chi-square test, Fisher's exact test, and t-test. RESULTS: The level of fatigue in the experimental group was significantly lower than the control group (t= - 2.74, p =.008). The level of cortisol in the urine of women in the experimental group was significantly lower than the control group (t= - 2.19, p =.032). The level of depression in the experimental group was significantly lower than the control group (t= - 3.00, p =.004). CONCLUSION: The results show that the foot reflexology massage is an effective nursing intervention to relieve fatigue, stress, and depression for postpartum women.

Determination of cortisol and cortisone in human saliva by a liquid chromatography-tandem mass spectrometry method / Determinação de cortisol e cortisona na saliva por método baseado em cromatografia líquida e espectrometria de massas em tandem

Objective Salivary cortisol measurement plays an important role in the evaluation of adrenal function. Its high correlation with free serum cortisol, the easy of sampling and the limited presence of interfering steroids, generated multiple recent studies of its application, in special in the screening of adrenal hyperfunction. In this paper we present our experience in the development of a high pressure liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method for salivary cortisol and cortisone measurement. Materials and methods For this study we used 181 saliva samples from our routine diagnostic laboratory. The HPLC-MS/MS method was based on a Waters Quattro Premier tandem mass spectrometer with an electrospray probe. After derivatization with hydroxylamine transitions monitored included cortisol and cortisone. An in-house radioimmunoassay (RIA) was used for salivary cortisol results comparison. Results Functional sensitivity was 24 ng/dL for cortisol and linearity from 24 to 1929 ng/dL. Saliva cortisol values obtained in the 181 samples presented a median of 52 ng/dL with 5‐95% percentile of 24 and 374 ng/dL. With the RIA the results were 86, 25 and 436 ng/dL, respectively, with values for RIA being significantly higher (P<0.0001) and high correlation (r=0.8312, P<0.0001). Cortisone measured in 159 samples showed a median of 278 ng/dL, with 5‐95% percentile of 100 and 1,133 ng/dL. Correlation with cortisol values was significant (r=0.820, P<0.0001). Conclusion We conclude that the HPLC-MS/MS method compares favorably with the RIA for salivary cortisol measurement, with the additional possibility of concomitant cortisone measurement and the evaluation of 11βHSD2 activity. .

Objetivo A dosagem de cortisol salivar é uma metodologia que vem tendo crescente aceitação no estudo da função adrenocortical. Sua alta correlação com a fração livre sérica, facilidade de coleta e presença limitada de interferentes têm originado múltiplas publicações, em especial no screening de pacientes suspeitos de hiperfunção. Neste trabalho apresentamos nossa experiência no desenvolvimento de metodologia baseada em cromatografia líquida e espectrometria de massas (HPLC-MS/MS) para a medida de cortisol e cortisona salivares. Materiais e métodos Para este estudo utilizamos 181 amostras de saliva de nossa rotina diagnóstica. A metodologia de HPLC-MS/MS baseou-se num espectrômetro de massas Waters Quattro Premier. Após derivatização com hidroxilamina, as transições monitoradas incluíram cortisol e cortisona. Um radioimunoensaio (RIE) in house foi empregado para comparação. Resultados A sensibilidade funcional para cortisol foi de 24 ng/dL, com linearidade entre 24 e 1,929 ng/dL. Os valores de cortisol obtidos nas 181 amostras apresentaram mediana de 52 ng/dL, com percentis 5‐95% de 24 e 374 ng/dL. Com o RIE, os resultados foram 86, 25 e 436 ng/L, respectivamente, com os valores obtidos no RIE significativamente mais elevados (P<0,0001), e alta correlação (r=0,8312, P<0,0001). Cortisona, medida em 159 amostras, mostrou mediana de 278 ng/dL, com percentis 5‐95% entre 100 e 1.133 ng/dL. A correlação com os valores de cortisol foi significativa (r=0,820, P<0,0001). Conclusão Concluímos que o método baseado em HPLC-MS/MS compara-se favoravelmente com o RIE para a medida de cortisol salivar, com a possibilidade adicional da medida concomitante de cortisona e avaliação da atividade da enzima 11βHSD2. .

Adipose tissue expression of 11beta-Hydroxysteroid dehydrogenase type 1 in cushing's syndrome and in obesity

Glucocorticoids have a major role in determining adipose tissue metabolism and distribution. 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1) is a NADPH-dependent enzyme highly expressed in the liver and adipose tissue. In most intact cells and tissues it functions as a reductase (to convert inactive cortisone to active cortisol). It has been hypothesized that tissue-specific deregulation of cortisol metabolism may be involved in the complex pathophysiology of the metabolic syndrome (MS) and obesity. Transgenic mice overexpressing 11betaHSD1 in adipose tissue develop obesity with all features of the MS, whereas 11betaHSD1-knockout mice are protected from both. The bulk of evidences points to an overexpression and increased activity of 11betaHSD1 also in human adipose tissue. However, 11betaHSD1 seems to adjust local cortisol concentrations independently of its plasma levels. In Cushing's syndrome, 11betaHSD1 is downregulated and may not be responsible for the abdominal fat depots; it also undergoes downregulation in response to weight loss in human obesity. The nonselective 11betaHSD1 inhibitor carbenoxolone improves insulin sensitivity in humans, and selective inhibitors enhance insulin action in diabetic mice liver, thereby lowering blood glucose. Thus, 11betaHSD1 is now emerging as a modulator of energy partitioning and a promising pharmacological target to treat the MS and diabetes.

Os glicocorticóides (GC) têm papel importante na determinação do metabolismo e da distribuição do tecido adiposo. A 11beta-hidroxisteróide desidrogenase tipo 1 (11betaHSD1) é uma enzima dependente de NADPH, altamente expressa nos tecidos hepático e adiposo. Em muitas células e tecidos intactos, ela funciona como redutase (convertendo cortisona em cortisol). Postula-se que uma desregulação tecido-específica do cortisol estaria envolvida na complexa fisiopatologia da síndrome metabólica (SM) e obesidade. Ratos que super-expressam 11betaHSD1 no tecido adiposo desenvolvem obesidade e todas as características da SM, enquanto ratos knockout para 11betaHSD1 são protegidos. Evidências apontam para uma super-expressão e aumento da atividade 11betaHSD1 também no tecido adiposo humano. Entretanto, a 11betaHSD1 parece ajustar a concentração local de cortisol independente da sua concentração sérica. Na síndrome de Cushing, a expressão da 11betaHSD1 é regulada para baixo, não devendo ser a causa dos depósitos de gordura visceral; em obesos, há também regulação para baixo em resposta à perda de peso. A carbenoxolona, um inibidor não seletivo da 11betaHSD1, melhora a sensibilidade insulínica em humanos e inibidores seletivos aumentam a sensibilidade insulínica hepática e melhoram o controle glicêmico em ratos diabéticos. Assim, a 11betaHSD1 está emergindo como um modulador da compartimentalização de energia e um alvo farmacológico promissor para o tratamento da SM e do diabetes.

CALCIUM IONOPHORE STRONGLY INHIBITS THE GENERATION OF EFFECTOR KILLERS FROM PROLIFERATIVE CYTOTOXIC T CELLS / 中国免疫学杂志

The Ly2~+ Cortisone-Resistant Thymocytes(CRT)were cultured in mediumcontaining IL2,CAS and various mitogens for 7 days.The cytolytic activityof effector CTL was assayed by ~(111)In-release cytotoxicity.At the K/T ratio32/1,the cytotoxicity of effector CTL generated from the stimulus of ConA,PMA.Calcium ionophore(CaI)and PMA+CaI was 46%,24%,13% and 5%respectively.This was the first time that the Cal showed a stronger effecton the inhibition of the generation of effector CTL than that of PMA.The inhibition of PMA and CaI on the differentiation of CTL could bepartially reversed by the removal of PMA and CaI-containing medium andreplaced with cytokine-containing fresh medium.The cytolytic activity wasincreased by three fold,but still 2.4 fold lower than that stimulated byConA at the same K/T ratio. The critical cytokine in the replaced medium was IL2 for the differentia-tion of CTL.Supplementation of IFNr,IL4 or CAS could not further increasethe cytotoxicity.However,the cytolytic activity was slightly increased whenIFNr was added at the initiation of culture. Early T cells could be induced to generate antigen-specific cytotoxic Tcells when cultured in the system with our designed protocol,

Influence of Hepatic Damage on the Male Reproductive Glands: IV. Effect of Cortisone on the Reproductive Glands of Male White Rats with Liver Damage / 대한비뇨기과학회지

Young adult male rats were injected with carbon tetrachloride along with cortisone acetate simultaneously and the effect of cortisone acetate on the damage of the liver and the liver's effect on the reproductive gland and its accessories were studied. The following results were obtained: Cortisone acetate given rats with damaged livers caused a very remarkable decrease in the weights of the accessory glands of reproduction, while the liver was restored to normal hepatic architecture. Judging from the marked weight decreases of the glands, cortisone acetate is thought to be responsible for enhancing the estrogenic effect through liver dysfunction despite the return to normal hepatic histology. Citric acid concentration in the prostatic tissue was not altered greatly by cortisone acetate administration. The concentration of the prostatic citrate can not be taken as an index of androgenic activity.

ELECTRON MICROSCOPY HISTOCHEMICAL OBSERVATION OF THE EFFECT OF CORTISONE ON THE ACID PHOSPHATASEOF NEUROHYPOPHYSIS / 解剖学报

Twenty-eight adult male rats were used for this study. The experimentar were injected intramuscular with 25 mg/d cortisone acetate and were killed in various intervals separately. The neurohypophysis were fixed in mixed solution of 4% paraformaldehyde and 2% glutaraldehyde in buffered cacodylate. Frozens ections were incubated in the medium of sodium glycero-phosphate and lead nitrate, postfixed in caulfield solution, dehydrated, embedded, ultrathin sectioned, stained With uranium acetate without lead citrate, and observed under EM, In the neurohypophysis of control animals, the active areas of acid phosphatase were few and were limited in lysosome and Golgi apparatus of pituicytes and endothelia of capillaries. After injection of cortisone, the lysosome of pituicytes were increased and the activity of acid phosphatase were strengthened. Besides pituicytes and endothelia cells, there were so many positive thin granules in the processes of dark pituicytes, some areas of positive reaction of AcP appeared in neurosecretion fibers. After increasing the drug dosage, positive reaction of AcP areas showed a tendency of expansion. In this study, we discussed the effect of cortisone on the AcP of neurohypophysis and the functional significance of pituicytes in neurosecretion procedure.