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[PMID]:28012176
[Au] Autor:Webster SP; McBride A; Binnie M; Sooy K; Seckl JR; Andrew R; Pallin TD; Hunt HJ; Perrior TR; Ruffles VS; Ketelbey JW; Boyd A; Walker BR
[Ad] Endereço:Centre for Cardiovascular Science, University of Edinburgh, Queen's Medical Research Institute, Edinburgh, UK.
[Ti] Título:Selection and early clinical evaluation of the brain-penetrant 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) inhibitor UE2343 (Xanamem™).
[So] Source:Br J Pharmacol;174(5):396-408, 2017 Mar.
[Is] ISSN:1476-5381
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND AND PURPOSE: Reducing glucocorticoid exposure in the brain via intracellular inhibition of the cortisol-regenerating enzyme 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) has emerged as a therapeutic strategy to treat cognitive impairment in early Alzheimer's disease (AD). We sought to discover novel, brain-penetrant 11ß-HSD1 inhibitors as potential medicines for the treatment of AD. EXPERIMENTAL APPROACH: Medicinal chemistry optimization of a series of amido-thiophene analogues was performed to identify potent and selective 11ß-HSD1 inhibitors with optimized oral pharmacokinetics able to access the brain. Single and multiple ascending dose studies were conducted in healthy human subjects to determine the safety, pharmacokinetic and pharmacodynamic characteristics of the candidate compound. RESULTS: UE2343 was identified as a potent, orally bioavailable, brain-penetrant 11ß-HSD1 inhibitor and selected for clinical studies. No major safety issues occurred in human subjects. Plasma adrenocorticotropic hormone was elevated (a marker of systemic enzyme inhibition) at doses of 10 mg and above, but plasma cortisol levels were unchanged. Following multiple doses of UE2343, plasma levels were approximately dose proportional and the terminal t ranged from 10 to 14 h. The urinary tetrahydrocortisols/tetrahydrocortisone ratio was reduced at doses of 10 mg and above, indicating maximal 11ß-HSD1 inhibition in the liver. Concentrations of UE2343 in the CSF were 33% of free plasma levels, and the peak concentration in CSF was ninefold greater than the UE2343 IC . CONCLUSIONS AND IMPLICATIONS: UE2343 is safe, well tolerated and reaches the brain at concentrations predicted to inhibit 11ß-HSD1. UE2343 is therefore a suitable candidate to test the hypothesis that 11ß-HSD1 inhibition in brain improves memory in patients with AD.
[Mh] Termos MeSH primário: 11-beta-Hidroxiesteroide Desidrogenase Tipo 1/antagonistas & inibidores
Encéfalo/metabolismo
Inibidores Enzimáticos/administração & dosagem
Tiofenos/administração & dosagem
Tropanos/administração & dosagem
[Mh] Termos MeSH secundário: Adolescente
Adulto
Animais
Cães
Relação Dose-Resposta a Droga
Método Duplo-Cego
Inibidores Enzimáticos/efeitos adversos
Inibidores Enzimáticos/farmacocinética
Feminino
Meia-Vida
Seres Humanos
Hidrocortisona/sangue
Concentração Inibidora 50
Masculino
Meia-Idade
Ratos
Ratos Sprague-Dawley
Tetra-Hidrocortisol/urina
Tetra-Hidrocortisona/urina
Tiofenos/efeitos adversos
Tiofenos/farmacocinética
Distribuição Tecidual
Tropanos/efeitos adversos
Tropanos/farmacocinética
Adulto Jovem
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Enzyme Inhibitors); 0 (Thiophenes); 0 (Tropanes); 0 (UE2343); 5HF9TM2D15 (Tetrahydrocortisone); 7P2O6MFN8O (Tetrahydrocortisol); EC 1.1.1.146 (11-beta-Hydroxysteroid Dehydrogenase Type 1); WI4X0X7BPJ (Hydrocortisone)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170922
[Lr] Data última revisão:
170922
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161225
[St] Status:MEDLINE
[do] DOI:10.1111/bph.13699


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[PMID]:27310211
[Au] Autor:Chiesa L; Panseri S; Pavlovic R; Cannizzo FT; Biolatti B; Divari S; Villa R; Arioli F
[Ad] Endereço:a Department of Veterinary Science and Public Health , University of Milan , Milan , Italy.
[Ti] Título:HPLC-ESI-MS/MS assessment of the tetrahydro-metabolites of cortisol and cortisone in bovine urine: promising markers of dexamethasone and prednisolone treatment.
[So] Source:Food Addit Contam Part A Chem Anal Control Expo Risk Assess;33(7):1175-89, 2016 Jul.
[Is] ISSN:1944-0057
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo: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 11ß-hydroxysteroid dehydrogenases (11ßHSDs), 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 5ß-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 11ßHSD 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-invasive procedure for assessing the impact of synthetic glucocorticosteroids administration.
[Mh] Termos MeSH primário: Cortisona/urina
Dexametasona/urina
Hidrocortisona/urina
Prednisolona/urina
Tetra-Hidrocortisol/análogos & derivados
Tetra-Hidrocortisona/urina
[Mh] Termos MeSH secundário: 11-beta-Hidroxiesteroide Desidrogenases/antagonistas & inibidores
11-beta-Hidroxiesteroide Desidrogenases/urina
Animais
Biomarcadores/urina
Biotransformação
Bovinos
Cromatografia Líquida de Alta Pressão
Dexametasona/farmacologia
Masculino
Oxirredutases atuantes sobre Doadores de Grupo CH-CH/antagonistas & inibidores
Oxirredutases atuantes sobre Doadores de Grupo CH-CH/urina
Prednisolona/farmacologia
Espectrometria de Massas por Ionização por Electrospray
Estereoisomerismo
Espectrometria de Massas em Tandem
Tetra-Hidrocortisol/urina
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers); 302-91-0 (allotetrahydrocortisol); 5HF9TM2D15 (Tetrahydrocortisone); 7P2O6MFN8O (Tetrahydrocortisol); 7S5I7G3JQL (Dexamethasone); 9PHQ9Y1OLM (Prednisolone); EC 1.1.1.146 (11-beta-Hydroxysteroid Dehydrogenases); EC 1.3.- (Oxidoreductases Acting on CH-CH Group Donors); EC 1.3.1.22 (cortisone alpha-reductase); V27W9254FZ (Cortisone); WI4X0X7BPJ (Hydrocortisone)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170303
[Lr] Data última revisão:
170303
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160617
[St] Status:MEDLINE
[do] DOI:10.1080/19440049.2016.1202453


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[PMID]:26493852
[Au] Autor:Kamrath C; Hartmann MF; Boettcher C; Zimmer KP; Wudy SA
[Ad] Endereço:Division of Pediatric Endocrinology and Diabetology, Laboratory for Translational Hormone Analysis in Pediatric Endocrinology, Steroid Research and Mass Spectromity Unit, Center of Child and Adolescent Medicine, Justus Liebig University, Giessen, Germany. Electronic address: Clemens.kamrath@paediat.
[Ti] Título:Diagnosis of 21-hydroxylase deficiency by urinary metabolite ratios using gas chromatography-mass spectrometry analysis: Reference values for neonates and infants.
[So] Source:J Steroid Biochem Mol Biol;156:10-6, 2016 Feb.
[Is] ISSN:1879-1220
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:One major issue of newborn screening programs for 21-hydroxylase deficiency (21OHD) is the high rate of false-positive results, especially in preterm neonates. Urinary steroid metabolite analysis using gas chromatography-mass spectrometry (GC-MS) is suitable as a confirmatory diagnostic tool. The objective of this study was to analyze retrospectively diagnostic metabolite ratios in neonates and infants with and without 21OHD using GC-MS with emphasis on glucocorticoid metabolism, and to develop reference values for the steroid metabolite ratios for the diagnosis of 21OHD. We retrospectively analyzed urinary steroid hormone metabolites determined by GC-MS of 95 untreated neonates and infants with 21OHD (1-148 days), and 261 neonates and infants (100 preterms) without 21OHD (0-217 days). Metabolites of 17α-hydroxyprogesterone showed specificities below 98%, whereas the 21-deoxycortisol metabolite pregnanetriolone clearly separated 21OHD from non-21OHD subjects. The best diagnostic ratio for 21OHD was pregnanetriolone to 6α-hydroxy-tetrahydrocortisone. The lowest value of this ratio in the 21OHD group (0.47) was at least eight times higher than the highest values in the non-21OHD group (0.055). We have given appropriate reference values for steroid metabolite ratios in the largest 21OHD cohort so far described. Consideration of glucocorticoid metabolism, especially the use of typical neonatal 6α-hydroxylates metabolites, leads to improvement of diagnostic metabolite ratios.
[Mh] Termos MeSH primário: Hiperplasia Suprarrenal Congênita/diagnóstico
Hiperplasia Suprarrenal Congênita/urina
Cromatografia Gasosa-Espectrometria de Massas/métodos
Metabolômica/métodos
[Mh] Termos MeSH secundário: Hiperplasia Suprarrenal Congênita/metabolismo
Estudos de Coortes
Feminino
Seres Humanos
Lactente
Recém-Nascido
Masculino
Pregnanotriol/análogos & derivados
Pregnanotriol/metabolismo
Pregnanotriol/urina
Valores de Referência
Esteroides/metabolismo
Esteroides/urina
Tetra-Hidrocortisona/análogos & derivados
Tetra-Hidrocortisona/metabolismo
Tetra-Hidrocortisona/urina
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (6 alpha-hydroxytetrahydrocortisone); 0 (Steroids); 27178-64-9 (Pregnanetriol); 5HF9TM2D15 (Tetrahydrocortisone); 603-99-6 (pregnanetriolone)
[Em] Mês de entrada:1605
[Cu] Atualização por classe:160103
[Lr] Data última revisão:
160103
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151024
[St] Status:MEDLINE


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[PMID]:26349936
[Au] Autor:Buehlmeier J; Remer T; Frings-Meuthen P; Maser-Gluth C; Heer M
[Ad] Endereço:Institute of Aerospace Medicine, German Aerospace Center (DLR), Linder Hoehe, 51147, Cologne, Germany. judith.buehlmeier@gmail.com.
[Ti] Título:Glucocorticoid activity and metabolism with NaCl-induced low-grade metabolic acidosis and oral alkalization: results of two randomized controlled trials.
[So] Source:Endocrine;52(1):139-47, 2016 Apr.
[Is] ISSN:1559-0100
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Low-grade metabolic acidosis (LGMA), as induced by high dietary acid load or sodium chloride (NaCl) intake, has been shown to increase bone and protein catabolism. Underlying mechanisms are not fully understood, but from clinical metabolic acidosis interactions of acid-base balance with glucocorticoid (GC) metabolism are known. We aimed to investigate GC activity/metabolism under alkaline supplementation and NaCl-induced LGMA. Eight young, healthy, normal-weight men participated in two crossover designed interventional studies. In Study A, two 10-day high NaCl diet (32 g/d) periods were conducted, one supplemented with 90 mmol KHCO3/day. In Study B, participants received a high and a low NaCl diet (31 vs. 3 g/day), each for 14 days. During low NaCl, the diet was moderately acidified by replacement of a bicarbonate-rich mineral water (consumed during high NaCl) with a non-alkalizing drinking water. In repeatedly collected 24-h urine samples, potentially bioactive-free GCs (urinary-free cortisol + free cortisone) were analyzed, as well as tetrahydrocortisol (THF), 5α-THF, and tetrahydrocortisone (THE). With supplementation of 90 mmol KHCO3, the marker of total adrenal GC secretion (THF + 5α-THF + THE) dropped (p = 0.047) and potentially bioactive-free GCs were reduced (p = 0.003). In Study B, however, GC secretion and potentially bioactive-free GCs did not exhibit the expected fall with NaCl-reduction as net acid excretion was raised by 30 mEq/d. Diet-induced acidification/alkalization affects GC activity and metabolism, which in case of long-term ingestion of habitually acidifying western diets may constitute an independent risk factor for bone degradation and cardiometabolic diseases.
[Mh] Termos MeSH primário: Acidose/induzido quimicamente
Acidose/metabolismo
Álcalis/farmacologia
Glucocorticoides/metabolismo
Cloreto de Sódio
[Mh] Termos MeSH secundário: Equilíbrio Ácido-Base/efeitos dos fármacos
Adulto
Bicarbonatos/farmacologia
Cortisona/urina
Estudos Cross-Over
Dieta
Água Potável
Glucocorticoides/urina
Seres Humanos
Hidrocortisona/urina
Masculino
Compostos de Potássio/farmacologia
Tetra-Hidrocortisol/urina
Tetra-Hidrocortisona/metabolismo
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Alkalies); 0 (Bicarbonates); 0 (Drinking Water); 0 (Glucocorticoids); 0 (Potassium Compounds); 451W47IQ8X (Sodium Chloride); 5HF9TM2D15 (Tetrahydrocortisone); 7P2O6MFN8O (Tetrahydrocortisol); HM5Z15LEBN (potassium bicarbonate); V27W9254FZ (Cortisone); WI4X0X7BPJ (Hydrocortisone)
[Em] Mês de entrada:1612
[Cu] Atualização por classe:171107
[Lr] Data última revisão:
171107
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150910
[St] Status:MEDLINE
[do] DOI:10.1007/s12020-015-0730-7


  5 / 197 MEDLINE  
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[PMID]:25668797
[Au] Autor:Zhai X; Chen F; Zhu C; Lu Y
[Ad] Endereço:Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, People's Republic of China.
[Ti] Título:A simple LC-MS/MS method for the determination of cortisol, cortisone and tetrahydro-metabolites in human urine: assay development, validation and application in depression patients.
[So] Source:J Pharm Biomed Anal;107:450-5, 2015 Mar 25.
[Is] ISSN:1873-264X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Chronic stress as well as major depressive disorders is associated with cortisol metabolism. Two enzymes modulate cortisol (F) and cortisone (E) interconversion: 11ß-hydroxysteroid dehydrogenase type 1 and type 2 (11ß-HSD1 and 11ß-HSD2). Furthermore, F and E were inactivated by 5α and 5ß reductases to their tetrahydro-metabolites: tetrahydrocortisol (THF), allo-tetrahydrocortisol (5α-THF) and tetrahydrocortisone (THE). To better understand depression a LC-MS/MS method for simultaneous determination of F, E THF, 5α-THF and THE in human urine has been developed and validated. The quantification range was 0.1-160 ng mL(-1) for F and E, and 0.2-160 ng mL(-1) for the tetrahydro-metabolites, with >86.1% recovery for all analytes. The nocturnal urine concentrations of F, E and tetrahydro-metabolites in 12 apparently healthy male adult volunteers and 12 drug-free male patients (age range, 20-50 years) with a diagnosis of depression were analyzed. A series of significant changes in glucocorticoid metabolism can be detected: F/E ratios and (THF+5α-THF)/THE ratios as well as F and THF concentrations were significantly higher in depression patients than in healthy subjects (p<0.05); 5α-THF/F ratios, 5α-THF/THF ratios as well as 5α-THF concentrations were significantly lower in depression patients (p<0.05). The results pointed to the decreased 11ß-HSD2 activity and a dysfunction in the 5α-reductase pathway in depressed patients. This method allows the assessment of 11ß-HSD1/2 and 5α/ß-reductase activities in a single analytical run providing an innovative tool to explain the potential etiology of depression.
[Mh] Termos MeSH primário: Cortisona/química
Cortisona/urina
Transtorno Depressivo Maior/urina
Hidrocortisona/química
Hidrocortisona/urina
Tetra-Hidrocortisona/química
Tetra-Hidrocortisona/urina
[Mh] Termos MeSH secundário: 11-beta-Hidroxiesteroide Desidrogenase Tipo 1/metabolismo
11-beta-Hidroxiesteroide Desidrogenase Tipo 2/metabolismo
Adulto
Estudos de Casos e Controles
Colestenona 5 alfa-Redutase/metabolismo
Cromatografia Líquida/métodos
Cortisona/metabolismo
Transtorno Depressivo Maior/metabolismo
Glucocorticoides/química
Glucocorticoides/metabolismo
Glucocorticoides/urina
Seres Humanos
Hidrocortisona/metabolismo
Masculino
Meia-Idade
Espectrometria de Massas em Tandem/métodos
Tetra-Hidrocortisol/análogos & derivados
Tetra-Hidrocortisol/química
Tetra-Hidrocortisol/metabolismo
Tetra-Hidrocortisol/urina
Tetra-Hidrocortisona/metabolismo
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Glucocorticoids); 302-91-0 (allotetrahydrocortisol); 5HF9TM2D15 (Tetrahydrocortisone); 7P2O6MFN8O (Tetrahydrocortisol); EC 1.1.1.146 (11-beta-Hydroxysteroid Dehydrogenase Type 1); EC 1.1.1.146 (11-beta-Hydroxysteroid Dehydrogenase Type 2); EC 1.1.1.146 (HSD11B2 protein, human); EC 1.3.1.22 (Cholestenone 5 alpha-Reductase); V27W9254FZ (Cortisone); WI4X0X7BPJ (Hydrocortisone)
[Em] Mês de entrada:1512
[Cu] Atualização por classe:150304
[Lr] Data última revisão:
150304
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150211
[St] Status:MEDLINE


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[PMID]:25492292
[Au] Autor:Hu X; Zhao Y; Chen B; Liang Y; Li L; Xie C; Zhang Y; Lin Z; Xie A; Chen S
[Ad] Endereço:Department of Pediatrics, Second Affiliated Hospital of WenZhou Medical University, Wenzhou 325027, China.
[Ti] Título:[11beta-hydroxysteroid dehydrogenase type 2 enzyme activity effect after exposures phthalate esters in maternal].
[So] Source:Zhonghua Yu Fang Yi Xue Za Zhi;48(9):800-4, 2014 Sep.
[Is] ISSN:0253-9624
[Cp] País de publicação:China
[La] Idioma:chi
[Ab] Resumo:OBJECTIVE: To study the association between phthalate esters (PAEs) metabolites in maternal urine and 11beta-hydroxysteroid dehydrogenase type 2 (11ß-HSD2 ) enzyme activity, explore the possible mechanism of PAEs effect on fetal development. METHODS: All of 33 cases of intrauterine growth retardation (IUGR) newborn were selected by random sampling in 2012. And 33 cases of normal control newborn were enrolled, use high performance liquid chromatography-tandem mass spectrometry method was used to detect 4 kinds of phthalate esters (PAEs) metabolites in maternal urine: mono-n-butyl phthalate ester (MBP), mono (2-ethylhexyl) phthalate (MEHP), mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono (2-ethyl-5-oxohexyl) phthalate (MEOHP) and three kinds of cortisol corticosterone metabolites, tetrahydrocortisol (THF), allo-tetrahydrocortisol (allo-THF), tetrahydrocortisone (THE), and analyze the association between phthalate esters (PAEs) metabolites in maternal urine and 11ß-HSD2 enzyme activity. RESULTS: MBP, MEHP, MEHHP, MEOHP metabolites can be detected in 98% (65 cases) , 89% (59 cases), 91% (60 cases), 91% (60 cases) of all 66 maternal urine samples, respectively. The median concentrations of test material in case group were 31.20 ng/ml for MBP, 24.61 ng/ml for MEHHP, 11.72 ng/ml for MEOHP and 48.67 ng/ml for SumDEHP which were significantly higher than those of the control group (were 17.32, 12.03, 5.68 and 28.64 ng/ml); 11ß-HSD2 activity in case group ((THF+allo-THF)/THE = (0.79 ± 0.09) ng/ml) was significantly lower than that of the control group((THF+allo-THF)/THE = (0.58 ± 0.04) ng/ml); PAEs metabolites MBP (ß' = 1.12), MEHHP(ß' = 1.14), MEOHP(ß' = 1.10), SumDEHP(ß' = 1.08) in baby boy mother's urine was reversely correlated to 11ß-HSD2 activity. CONCLUSIONS: PAEs could affect fetal development by inhibit 11ß-HSD2 activity.
[Mh] Termos MeSH primário: 11-beta-Hidroxiesteroide Desidrogenase Tipo 2
Dietilexilftalato/análogos & derivados
Desenvolvimento Fetal
Ácidos Ftálicos
[Mh] Termos MeSH secundário: Cromatografia Líquida
Seres Humanos
Recém-Nascido
Masculino
Espectrometria de Massas
Tetra-Hidrocortisol/análogos & derivados
Tetra-Hidrocortisona
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Phthalic Acids); 0 (mono(2-ethyl-5-hydroxyhexyl) phthalate); 302-91-0 (allotetrahydrocortisol); 40321-98-0 (mono(2-ethyl-5-oxohexyl)phthalate); 5HF9TM2D15 (Tetrahydrocortisone); 7P2O6MFN8O (Tetrahydrocortisol); C42K0PH13C (Diethylhexyl Phthalate); EC 1.1.1.146 (11-beta-Hydroxysteroid Dehydrogenase Type 2); FU2EWB60RT (mono-(2-ethylhexyl)phthalate); ZI46LWZ45G (monobutyl phthalate)
[Em] Mês de entrada:1509
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:141211
[St] Status:MEDLINE


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[PMID]:24534618
[Au] Autor:Steen NE; Methlie P; Lorentzen S; Dieset I; Aas M; Nerhus M; Haram M; Agartz I; Melle I; Berg JP; Andreassen OA
[Ad] Endereço:KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Drammen District Psychiatric Center, Clinic of Mental Health and Addiction, Vestre Viken Hospital Trust, Drammen
[Ti] Título:Altered systemic cortisol metabolism in bipolar disorder and schizophrenia spectrum disorders.
[So] Source:J Psychiatr Res;52:57-62, 2014 May.
[Is] ISSN:1879-1379
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis is suggested as a pathophysiological factor in bipolar disorder and schizophrenia. Increased clearance of cortisol was recently indicated as a component in the HPA axis hyperdrive. The aim of the present study was to test the model of increased cortisol metabolism in a new replication sample separately and combined with a previously published sample of bipolar disorder and schizophrenia. Spot urine was sampled from 212 healthy controls (HC) and 221 patients with a schizophrenia spectrum disorder (SCZ, n = 115) and bipolar disorder (BD, n = 106). Of these, a subsample of 169 HC and 155 patients was included in a previous report. Urinary free cortisol, cortisone and their metabolites were measured, and the activities of 5α-reductase, 5ß-reductase and 11ß-HSD were estimated and analyzed for differences between groups. In the new sample, there was increased enzyme activity in SCZ for 5ß-reductase (p = 0.024 vs HC; p = 0.027 vs BD) and 11ß-HSD2 (p = 0.014 vs HC; p = 0.004 vs BD). In the combined sample, there was increased activity in SCZ for 5α-reductase (p < 0.001 vs HC; p = 0.020 vs BD), 5ß-reductase (p < 0.001 vs HC; p = 0.045 vs BD) and 11ß-HSD2 (p < 0.001 vs HC; p = 0.043 vs BD), and in BD for 5ß-reductase (p = 0.002), 11ß-HSD2 (p = 0.039) and 5α-reductase (trend, p = 0.084) (all vs HC). The findings confirm increased systemic cortisol metabolism in BD and SCZ. This is most consistent in SCZ, with BD taking an intermediate position. The design makes it impossible to determine the direction of the effect. However, the findings merit further study of cortisol metabolism as a possible component in the HPA axis dysfunction and pathophysiology of BD and SCZ.
[Mh] Termos MeSH primário: Transtorno Bipolar/metabolismo
Hidrocortisona/metabolismo
Esquizofrenia/metabolismo
[Mh] Termos MeSH secundário: Adolescente
Adulto
Análise de Variância
Feminino
Seres Humanos
Masculino
Meia-Idade
Escalas de Graduação Psiquiátrica
Tetra-Hidrocortisol/análogos & derivados
Tetra-Hidrocortisol/metabolismo
Tetra-Hidrocortisona/metabolismo
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
302-91-0 (allotetrahydrocortisol); 5HF9TM2D15 (Tetrahydrocortisone); 7P2O6MFN8O (Tetrahydrocortisol); WI4X0X7BPJ (Hydrocortisone)
[Em] Mês de entrada:1501
[Cu] Atualização por classe:140314
[Lr] Data última revisão:
140314
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140219
[St] Status:MEDLINE


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[PMID]:24532078
[Au] Autor:Di Luigi L; Botrè F; Sabatini S; Sansone M; Mazzarino M; Guidetti L; Baldari C; Lenzi A; Caporossi D; Romanelli F; Sgrò P
[Ad] Endereço:Department of Movement, Human and Health Sciences, University of Rome "Foro Italico", Piazza Lauro de Bosis, 15, 00135, Rome, Italy, luigi.diluigi@uniroma4.it.
[Ti] Título:Acute effects of physical exercise and phosphodiesterase's type 5 inhibition on serum 11ß-hydroxysteroid dehydrogenases related glucocorticoids metabolites: a pilot study.
[So] Source:Endocrine;47(3):952-8, 2014 Dec.
[Is] ISSN:1559-0100
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Endogenous glucocorticoids (GC) rapidly increase after acute exercise, and the phosphodiesterase's type 5 inhibitor (PDE5i) tadalafil influences this physiological adaptation. No data exist on acute effects of both acute exercise and PDE5i administration on 11ß-hydroxysteroid dehydrogenases (11ß-HSDs)-related GC metabolites. We aimed to investigate the rapid effects of exercise on serum GC metabolites, with and without tadalafil administration. A double blind crossover study was performed in eleven healthy male volunteers. After the volunteers randomly received a short-term administration of placebo or tadalafil (20 mg/die for 2 days), a maximal exercise test to exhaustion on cycle ergometer was performed. Then, after a 2-week washout period, the volunteers were crossed over. Blood samples were collected before starting exercise and at 5 and 30 min of recovery (+5-Rec, +30-Rec). Serum ACTH, corticosterone (Cn), cortisol (F), cortisone (E), tetrahydrocortisol (THF), tetrahydrocortisone (THE), cortols, cortolones and respective ratios were evaluated. Pre-Ex THF was higher after tadalafil. Exercise increased ACTH, Cn, F, E, THE, cortols and cortolones after both placebo and tadalafil, and THF after placebo. The F/E ratio increased at +5-Rec and decreased at +30-Rec after placebo. Compared to placebo, after tadalafil lower ACTH, F and Cn, higher THF/F and THE/E, and not E (at +5-Rec) and F/E modifications were observed. Acute exercise rapidly influences serum GC metabolites concentrations. Tadalafil influences both GC adaptation and 11ß-HSDs activity during acute exercise. Additional researches on the effects of both exercise and PDE5i on tissue-specific 11ß-HSDs activity at rest and during physiological adaptation are warranted.
[Mh] Termos MeSH primário: 11-beta-Hidroxiesteroide Desidrogenases/metabolismo
Carbolinas/farmacologia
Exercício/fisiologia
Inibidores da Fosfodiesterase 5/farmacologia
[Mh] Termos MeSH secundário: Hormônio Adrenocorticotrópico/sangue
Adulto
Corticosterona/sangue
Cortisona/sangue
Estudos Cross-Over
Método Duplo-Cego
Seres Humanos
Hidrocortisona/sangue
Masculino
Projetos Piloto
Tadalafila
Tetra-Hidrocortisol/sangue
Tetra-Hidrocortisona/sangue
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Carbolines); 0 (Phosphodiesterase 5 Inhibitors); 5HF9TM2D15 (Tetrahydrocortisone); 742SXX0ICT (Tadalafil); 7P2O6MFN8O (Tetrahydrocortisol); 9002-60-2 (Adrenocorticotropic Hormone); EC 1.1.1.146 (11-beta-Hydroxysteroid Dehydrogenases); V27W9254FZ (Cortisone); W980KJ009P (Corticosterone); WI4X0X7BPJ (Hydrocortisone)
[Em] Mês de entrada:1507
[Cu] Atualização por classe:171107
[Lr] Data última revisão:
171107
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140218
[St] Status:MEDLINE
[do] DOI:10.1007/s12020-014-0185-2


  9 / 197 MEDLINE  
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[PMID]:23291109
[Au] Autor:Pavlovic R; Cannizzo FT; Panseri S; Biolatti B; Trutic N; Biondi PA; Chiesa L
[Ad] Endereço:Department of Veterinary Sciences and Public Health, Università degli Studi di Milano, Italy.
[Ti] Título:Tetrahydro-metabolites of cortisol and cortisone in bovine urine evaluated by HPLC-ESI-mass spectrometry.
[So] Source:J Steroid Biochem Mol Biol;135:30-5, 2013 May.
[Is] ISSN:1879-1220
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Interconversion of hormonally active cortisol (F) into the corresponding inactive 11-keto form, cortisone (E), is catalyzed by 11beta-hydroxysteroid dehydrogenases (11ß-HSDs). With a view to estimating in vivo activities of some 11ß-HSD isoforms, the measurement of urinary F and E and their tetrahydro metabolites (tetrahydrocortisol, THF, allotetrahydrocortisol, ATHF, tetrahydrocortisone, THE) has been suggested. The basic knowledge of THF, ATHF and THE levels in farm cattle is limited. Therefore the aim of this study was first to optimize a simple and quick method to determine F and E tetrahydro-metabolites in bovine urine by HPLC-mass spectrometry with electrospray ionization (HPLC-ESI-MS) and then to apply the method to real urine of bovines treated with prednisolone. The samples underwent filtration, deconjugation, solid-phase extraction (SPE) and the relevant analytes were measured by HPLC-ESI-MS. The method described in this paper is simple and efficient, featuring good linearity (up to 0.996) and reproducibility (6.8-12.5%, CV). Especially, good LODs were obtained, from 1.63 to 2.67 ppb, depending on the analyte. The chromatographic conditions were optimized in order to obtain a resolution which would allow to simultaneously measure two diastereoisomers, i.e. THF and ATHF. In our study, ATHF turns out to be below the detection limit, while for 18 samples tested the contents of examinated metabolites were as followed: THF (12.5±4.8 ppb), THE (10.9±5.5 ppb), F (11.6±3.3 ppb) and E (5.0±2.2 ppb). When the method was applied to the subject treated with prednisolone a major increase in the concentration of tetrahydro metabolites was observed before the slaughter, mainly due to stress conditions; prednisolone treatment, most presumably, influenced the 11ß-HSD activity, as indicated by the decrease in the F/E ratio. This work may provide a useful methodological contribution to the future definition of F, E, THF, ATHF and THE urinary baseline values in order to obtain indirect evaluations of HSDs activity in farm cattle and possible applications in screenings for suspected abuse of synthetic corticosteroids in bovines.
[Mh] Termos MeSH primário: Cortisona/metabolismo
Hidrocortisona/metabolismo
Tetra-Hidrocortisol/urina
Tetra-Hidrocortisona/urina
[Mh] Termos MeSH secundário: Animais
Bovinos
Cromatografia Líquida de Alta Pressão
Masculino
Espectrometria de Massas por Ionização por Electrospray
Tetra-Hidrocortisol/análogos & derivados
Urinálise
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
302-91-0 (allotetrahydrocortisol); 5HF9TM2D15 (Tetrahydrocortisone); 7P2O6MFN8O (Tetrahydrocortisol); V27W9254FZ (Cortisone); WI4X0X7BPJ (Hydrocortisone)
[Em] Mês de entrada:1305
[Cu] Atualização por classe:131121
[Lr] Data última revisão:
131121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:130108
[St] Status:MEDLINE


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[PMID]:22233384
[Au] Autor:Rask E; Simonyte K; Lönn L; Axelson M
[Ad] Endereço:Department of Medicine, Örebro University Hospital, Örebro University, Örebro, Sweden.
[Ti] Título:Cortisol metabolism after weight loss: associations with 11 ß-HSD type 1 and markers of obesity in women.
[So] Source:Clin Endocrinol (Oxf);78(5):700-5, 2013 May.
[Is] ISSN:1365-2265
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: Increased glucocorticoid metabolite excretion and enhanced expression and activity of 11ß-hydroxysteroid dehydrogenase type 1 in adipose tissue are closely correlated with obesity and its detrimental consequences. Weight loss ameliorates the latter. The aim of this study was to explore whether increased glucocorticoid exposure in obesity is improved with substantial weight loss and thus is a consequence rather than a cause of obesity. DESIGN AND PATIENTS: A prospective cohort study in 31 women. MEASUREMENTS: 11ß-HSD type 1 expression and activity, urinary glucocorticoid metabolite excretion, body composition including regional adipose tissue depots and insulin resistance by HOMA-IR before and 2 years after gastric bypass surgery. RESULTS: After weight loss, excretion of cortisol and cortisone metabolites decreased. Both cortisol and cortisone metabolite excretion correlated with central obesity, where the intraabdominal fat depot showed the strongest association. Cortisol metabolites correlated with 11ß-HSD type 1 activity in abdominal subcutaneous adipose tissue. The ratio of cortisol to cortisone metabolites [(5α-tetrahydrocortisol (5αTHF) + tetrahydrocortisol (THF) + α-cortol)/(tetrahydrocortisone (THE) + α-cortolone)] and the ratio of 5α-THF/THF both decreased after stable weight loss, reflecting a downregulation of the net activities of 11ß-HSD type 1 and 5α-reductase. CONCLUSION: Long-term weight loss in women is not only followed by reduced glucocorticoid production, but also favourably decreases the global and tissue-specific activity of the cortisol-activating enzyme 11 ß-HSD type 1, possibly contributing to the health benefits of bariatric surgery.
[Mh] Termos MeSH primário: 11-beta-Hidroxiesteroide Desidrogenase Tipo 1/metabolismo
Hidrocortisona/urina
Obesidade/metabolismo
Obesidade/urina
Perda de Peso/fisiologia
[Mh] Termos MeSH secundário: Adulto
Estudos de Coortes
Cortisona/urina
Feminino
Seres Humanos
Meia-Idade
Estudos Prospectivos
Tetra-Hidrocortisol/metabolismo
Tetra-Hidrocortisona/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
5HF9TM2D15 (Tetrahydrocortisone); 7P2O6MFN8O (Tetrahydrocortisol); EC 1.1.1.146 (11-beta-Hydroxysteroid Dehydrogenase Type 1); V27W9254FZ (Cortisone); WI4X0X7BPJ (Hydrocortisone)
[Em] Mês de entrada:1309
[Cu] Atualização por classe:131121
[Lr] Data última revisão:
131121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:120112
[St] Status:MEDLINE
[do] DOI:10.1111/j.1365-2265.2012.04333.x



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