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[PMID]:28514642
[Au] Autor:Gu C; Tan H; Yang J; Lu Y; Ma Y
[Ad] Endereço:Department of Medical Genetics and Division of Human Morbid Genomics, West China Hospital, Sichuan University, Chengdu, China.
[Ti] Título:Congenital adrenal hyperplasia due to 11-hydroxylase deficiency-Compound heterozygous mutations of a prevalent and two novel CYP11B1 mutations.
[So] Source:Gene;626:89-94, 2017 Aug 30.
[Is] ISSN:1879-0038
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:11ß-hydroxylase deficiency (11ß-OHD) occurs in about 5-8% of congenital adrenal hyperplasia (CAH). In this study, we identified three CYP11B1 (encoding Cytochrome P450 11B1) heterozygous mutations: c.1358G>C (p.R453Q), c.1229T>G (p.L410R) and c.1231G>T (p.G411C) in a Chinese CAH patient due to classic 11ß-OHD. His parents were healthy and respectively carried the prevalent mutation c.1358G>C (p.R453Q), and the two novel mutations c.1229T>G (p.L410R) and c.1231G>T (p.G411C). In vitro expression studies, immunofluorescence demonstrated that wild type and mutant (L410R and G411C) proteins of CYP11B1 were correctly expressed on the mitochondria, and enzyme activity assay revealed the mutant reduced the 11-hydroxylase activity to 10% (P<0.001) for the conversion of 11ß-deoxycortisol to cortisol. Subsequently, three dimensional homology models for the normal and mutant proteins were built by using the x-ray structure of the human CYP11B2 as a template. Interestingly, in the heme binding site I helix, a change from helix to loop in four amino acide took place in the mutant model. In conclusion, this study expands the spectrum of mutations in CYP11B1 causing to 11ß-OHD and provides evidence for prenatal diagnosis and genetic counseling. In addition, our results confirm the two novel CYP11B1 mutations led to impaired 11-hydroxylase activity in vitro.
[Mh] Termos MeSH primário: Hiperplasia Suprarrenal Congênita/genética
Mutação de Sentido Incorreto
Esteroide 11-beta-Hidroxilase/genética
[Mh] Termos MeSH secundário: Hiperplasia Suprarrenal Congênita/diagnóstico
Adulto
Sítios de Ligação
Cortodoxona/metabolismo
Feminino
Células HEK293
Heme/metabolismo
Heterozigoto
Seres Humanos
Masculino
Linhagem
Ligação Proteica
Esteroide 11-beta-Hidroxilase/química
Esteroide 11-beta-Hidroxilase/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
42VZT0U6YR (Heme); EC 1.14.15.4 (Steroid 11-beta-Hydroxylase); WDT5SLP0HQ (Cortodoxone)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170727
[Lr] Data última revisão:
170727
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170518
[St] Status:MEDLINE


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[PMID]:28472487
[Au] Autor:Turcu AF; Mallappa A; Elman MS; Avila NA; Marko J; Rao H; Tsodikov A; Auchus RJ; Merke DP
[Ad] Endereço:Division of Metabolism, Endocrinology and Diabetes, University of Michigan, Ann Arbor, Michigan 48109.
[Ti] Título:11-Oxygenated Androgens Are Biomarkers of Adrenal Volume and Testicular Adrenal Rest Tumors in 21-Hydroxylase Deficiency.
[So] Source:J Clin Endocrinol Metab;102(8):2701-2710, 2017 Aug 01.
[Is] ISSN:1945-7197
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Context: Patients with 21-hydroxylase deficiency (21OHD) have long-term complications, resulting from poor disease control and/or glucocorticoid overtreatment. Lack of optimal biomarkers has made it challenging to tailor therapy and predict long-term outcomes. Objective: To identify biomarkers of disease control and long-term complications in 21OHD. Setting and Participants: Cross-sectional study of 114 patients (70 males), ages 2 to 67 years (median, 15 years), seen in a tertiary referral center. Methods: We correlated a mass-spectrometry panel of 23 steroids, obtained before first morning medication, with bone age advancement (children), adrenal volume (adults), testicular adrenal rest tumors (TART), hirsutism, menstrual disorders, and pituitary hormones. Results: Total adrenal volume correlated positively with 18 steroids, most prominently 21-deoxycortisol and four 11-oxygenated-C19 (11oxC19) steroids: 11ß-hydroxyandrostenedione (11OHA4), 11-ketoandrostenedione (11ketoA4), 11ß-hydroxytestosterone (11OHT), and 11-ketotestosterone (11ketoT) (r ≈ 0.7, P < 0.0001). Nine steroids were significantly higher (P ≤ 0.01) in males with TART compared with those without TART, including 11OHA4 (6.8-fold), 11OHT (4.9-fold), 11ketoT (3.6-fold), 11ketoA4 (3.3-fold), and pregnenolone sulfate (PregS; 4.8-fold). PregS (28.5-fold) and 17-hydroxypregnenolone sulfate (19-fold) levels were higher (P < 0.01) in postpubertal females with menstrual disorders. In males, testosterone levels correlated positively with all 11oxC19 steroids in Tanner stages 1 and 2 (r ≈ 0.7; P < 0.001) but negatively in Tanner stage 5 (r = -0.3 and P < 0.05 for 11ketoA4 and 11ketoT). In females, testosterone level correlated positively with all four 11oxC19 steroids across all Tanner stages (r ≈ 0.8; P < 0.0001). Conclusion: 11oxC19 steroids and PregS might serve as clinically useful biomarkers of disease control and long-term complications in 21OHD.
[Mh] Termos MeSH primário: Hiperplasia Suprarrenal Congênita/metabolismo
Tumor de Resto Suprarrenal/metabolismo
Androgênios/metabolismo
Hirsutismo/metabolismo
Distúrbios Menstruais/metabolismo
Neoplasias Testiculares/metabolismo
[Mh] Termos MeSH secundário: 17-alfa-Hidroxipregnenolona/análogos & derivados
17-alfa-Hidroxipregnenolona/metabolismo
Adolescente
Glândulas Suprarrenais/patologia
Adulto
Determinação da Idade pelo Esqueleto
Idoso
Androstenodiona/análogos & derivados
Androstenodiona/metabolismo
Androstenos/metabolismo
Criança
Pré-Escolar
Cortodoxona/metabolismo
Estudos Transversais
Feminino
Seres Humanos
Hidroxitestosteronas/metabolismo
Masculino
Meia-Idade
Tamanho do Órgão
Pregnenolona/metabolismo
Testosterona/análogos & derivados
Testosterona/metabolismo
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Androgens); 0 (Androstenes); 0 (Hydroxytestosterones); 04Y4D91RG0 (pregnenolone sulfate); 1816-85-9 (11-hydroxytestosterone); 28901-70-4 (17-hydroxypregnenolone sulfate); 387-79-1 (17-alpha-Hydroxypregnenolone); 3XMK78S47O (Testosterone); 409J2J96VR (Androstenedione); 564-32-9 (11-hydroxyandrostenedione); 641-77-0 (21-deoxycortisol); 73R90F7MQ8 (Pregnenolone); AE4E9102GY (adrenosterone); KF38W1A85U (11-ketotestosterone); WDT5SLP0HQ (Cortodoxone)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170920
[Lr] Data última revisão:
170920
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE
[do] DOI:10.1210/jc.2016-3989


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[PMID]:28333238
[Au] Autor:Abbott DH; Rayome BH; Dumesic DA; Lewis KC; Edwards AK; Wallen K; Wilson ME; Appt SE; Levine JE
[Ad] Endereço:Department of Obstetrics and Gynecology, University of Wisconsin, Madison, WI, USA.
[Ti] Título:Clustering of PCOS-like traits in naturally hyperandrogenic female rhesus monkeys.
[So] Source:Hum Reprod;32(4):923-936, 2017 04 01.
[Is] ISSN:1460-2350
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Study question: Do naturally occurring, hyperandrogenic (≥1 SD of population mean testosterone, T) female rhesus monkeys exhibit traits typical of women with polycystic ovary syndrome (PCOS)? Summary answer: Hyperandrogenic female monkeys exhibited significantly increased serum levels of androstenedione (A4), 17-hydroxyprogesterone (17-OHP), estradiol (E2), LH, antimullerian hormone (AMH), cortisol, 11-deoxycortisol and corticosterone, as well as increased uterine endometrial thickness and evidence of reduced fertility, all traits associated with PCOS. What is known already: Progress in treating women with PCOS is limited by incomplete knowledge of its pathogenesis and the absence of naturally occurring PCOS in animal models. A female macaque monkey, however, with naturally occurring hyperandrogenism, anovulation and polyfollicular ovaries, accompanied by insulin resistance, increased adiposity and endometrial hyperplasia, suggests naturally occurring origins for PCOS in nonhuman primates. Study design, size, duration: As part of a larger study, circulating serum concentrations of selected pituitary, ovarian and adrenal hormones, together with fasted insulin and glucose levels, were determined in a single, morning blood sample obtained from 120 apparently healthy, ovary-intact, adult female rhesus monkeys (Macaca mulatta) while not pregnant or nursing. The monkeys were then sedated for somatometric and ultrasonographic measurements. Participants/materials, setting, methods: Female monkeys were of prime reproductive age (7.2 ± 0.1 years, mean ± SEM) and represented a typical spectrum of adult body weight (7.4 ± 0.2 kg; maximum 12.5, minimum 4.6 kg). Females were defined as having normal (n = 99) or high T levels (n = 21; ≥1 SD above the overall mean, 0.31 ng/ml). Electronic health records provided menstrual and fecundity histories. Steroid hormones were determined by tandem LC-MS-MS; AMH was measured by enzymeimmunoassay; LH, FSH and insulin were determined by radioimmunoassay; and glucose was read by glucose meter. Most analyses were limited to 80 females (60 normal T, 20 high T) in the follicular phase of a menstrual cycle or anovulatory period (serum progesterone <1 ng/ml). Main results and the role of chance: Of 80 monkeys, 15% (n = 12) exhibited classifiable PCOS-like phenotypes. High T females demonstrated elevations in serum levels of LH (P < 0.036), AMH (P < 0.021), A4 (P < 0.0001), 17-OHP (P < 0.008), E2 (P < 0.023), glucocorticoids (P < 0.02-0.0001), the serum T/E2 ratio (P < 0.03) and uterine endometrial thickness (P < 0.014) compared to normal T females. Within the high T group alone, anogenital distance, a biomarker for fetal T exposure, positively correlated (P < 0.015) with serum A4 levels, while clitoral volume, a biomarker for prior T exposure, positively correlated (P < 0.002) with postnatal age. Only high T females demonstrated positive correlations between serum LH, and both T and A4. Five of six (83%) high T females with serum T ≥2 SD above T mean (0.41 ng/ml) did not produce live offspring. Large scale data: N/A. Limitations, reasons for caution: This is an initial study of a single laboratory population in a single nonhuman primate species. While two biomarkers suggest lifelong hyperandrogenism, phenotypic expression during gestation, prepuberty, adolescence, mid-to-late reproductive years and postmenopause has yet to be determined. Wider implications of the findings: Characterizing adult female monkeys with naturally occurring hyperandrogenism has identified individuals with high LH and AMH combined with infertility, suggesting developmental linkage among traits with endemic origins beyond humans. PCOS may thus be an ancient phenotype, as previously proposed, with a definable pathogenic mechanism(s). Study funding/competing interest(s): Funded by competitive supplement to P51 OD011106 (PI: Mallick), by P50 HD028934 (PI: Marshall) and by P50 HD044405 (PI: Dunaif). The authors have no potential conflicts of interest.
[Mh] Termos MeSH primário: Hiperandrogenismo/patologia
Síndrome do Ovário Policístico/patologia
[Mh] Termos MeSH secundário: Androstenodiona/sangue
Animais
Hormônio Antimülleriano/sangue
Corticosterona/sangue
Cortodoxona/sangue
Endométrio/patologia
Estradiol/sangue
Feminino
Fertilidade
Hidrocortisona/sangue
Hidroxiprogesteronas/sangue
Hiperandrogenismo/metabolismo
Hiperandrogenismo/fisiopatologia
Macaca mulatta
Fenótipo
Síndrome do Ovário Policístico/metabolismo
Síndrome do Ovário Policístico/fisiopatologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Hydroxyprogesterones); 409J2J96VR (Androstenedione); 4TI98Z838E (Estradiol); 80497-65-0 (Anti-Mullerian Hormone); W980KJ009P (Corticosterone); WDT5SLP0HQ (Cortodoxone); WI4X0X7BPJ (Hydrocortisone)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171017
[Lr] Data última revisão:
171017
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170324
[St] Status:MEDLINE
[do] DOI:10.1093/humrep/dex036


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[PMID]:28126345
[Au] Autor:Clifford AM; Bury NR; Schultz AG; Ede JD; Goss BL; Goss GG
[Ad] Endereço:Bamfield Marine Sciences Centre, Bamfield, BC, Canada; Department of Biological Sciences, University of Alberta, Edmonton, AB, Canada.
[Ti] Título:Regulation of plasma glucose and sulfate excretion in Pacific hagfish, Eptatretus stoutii is not mediated by 11-deoxycortisol.
[So] Source:Gen Comp Endocrinol;247:107-115, 2017 Jun 01.
[Is] ISSN:1095-6840
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The goal of this study was to identify whether Pacific hagfish (Eptatretus stoutii) possess glucocorticoid and mineralocorticoid responses and to examine the potential role(s) of four key steroids in these responses. Pacific hagfish were injected with varying amounts of cortisol, corticosterone or 11-deoxycorticosterone (DOC) using coconut oil implants and plasma glucose and gill total-ATPase activity were monitored as indices of glucocorticoid and mineralocorticoid responses. Furthermore, we also monitored plasma glucose and 11-deoxycortisol (11-DOC) levels following exhaustive stress (30 min of agitation) or following repeated infusion with SO . There were no changes in gill total-ATPase following implantation with any steroid, with only very small statistical increases in plasma glucose noted in hagfish implanted with either DOC (at 20 and 200mgkg at 7 and 4days post-injection, respectively) or corticosterone (at 100mgkg at 7days post-injection). Following exhaustive stress, hagfish displayed a large and sustained increase in plasma glucose. Repeated infusion of SO into hagfish caused increases in both plasma glucose levels and SO excretion rate suggesting a regulated glucocorticoid and mineralocorticoid response. However, animals under either condition did not show any significant increases in plasma 11-DOC concentrations. Our results suggest that while there are active glucocorticoid and mineralocorticoid responses in hagfish, 11-DOC does not appear to be involved and the identity and primary function of the steroid in hagfish remains to be elucidated.
[Mh] Termos MeSH primário: Glicemia/metabolismo
Cortodoxona/metabolismo
Feiticeiras (Peixe)/fisiologia
Sulfatos/metabolismo
[Mh] Termos MeSH secundário: Animais
Vias Biossintéticas
Óleo de Coco
Corticosterona/biossíntese
Óleos Vegetais/farmacologia
Estresse Fisiológico
Sulfatos/sangue
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Blood Glucose); 0 (Plant Oils); 0 (Sulfates); Q9L0O73W7L (Coconut Oil); W980KJ009P (Corticosterone); WDT5SLP0HQ (Cortodoxone)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170128
[St] Status:MEDLINE


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[PMID]:27845856
[Au] Autor:Jones CM; Mallappa A; Reisch N; Nikolaou N; Krone N; Hughes BA; O'Neil DM; Whitaker MJ; Tomlinson JW; Storbeck KH; Merke DP; Ross RJ; Arlt W
[Ad] Endereço:Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, B15 2TT, United Kingdom.
[Ti] Título:Modified-Release and Conventional Glucocorticoids and Diurnal Androgen Excretion in Congenital Adrenal Hyperplasia.
[So] Source:J Clin Endocrinol Metab;102(6):1797-1806, 2017 Jun 01.
[Is] ISSN:1945-7197
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Context: The classic androgen synthesis pathway proceeds via dehydroepiandrosterone, androstenedione, and testosterone to 5α-dihydrotestosterone. However, 5α-dihydrotestosterone synthesis can also be achieved by an alternative pathway originating from 17α-hydroxyprogesterone (17OHP), which accumulates in congenital adrenal hyperplasia (CAH). Similarly, recent work has highlighted androstenedione-derived 11-oxygenated 19-carbon steroids as active androgens, and in CAH, androstenedione is generated directly from 17OHP. The exact contribution of alternative pathway activity to androgen excess in CAH and its response to glucocorticoid (GC) therapy is unknown. Objective: We sought to quantify classic and alternative pathway-mediated androgen synthesis in CAH, their diurnal variation, and their response to conventional GC therapy and modified-release hydrocortisone. Methods: We used urinary steroid metabolome profiling by gas chromatography-mass spectrometry for 24-hour steroid excretion analysis, studying the impact of conventional GCs (hydrocortisone, prednisolone, and dexamethasone) in 55 adults with CAH and 60 controls. We studied diurnal variation in steroid excretion by comparing 8-hourly collections (23:00-7:00, 7:00-15:00, and 15:00-23:00) in 16 patients with CAH taking conventional GCs and during 6 months of treatment with modified-release hydrocortisone, Chronocort. Results: Patients with CAH taking conventional GCs showed low excretion of classic pathway androgen metabolites but excess excretion of the alternative pathway signature metabolites 3α,5α-17-hydroxypregnanolone and 11ß-hydroxyandrosterone. Chronocort reduced 17OHP and alternative pathway metabolite excretion to near-normal levels more consistently than other GC preparations. Conclusions: Alternative pathway-mediated androgen synthesis significantly contributes to androgen excess in CAH. Chronocort therapy appears superior to conventional GC therapy in controlling androgen synthesis via alternative pathways through attenuation of their major substrate, 17OHP.
[Mh] Termos MeSH primário: Hiperplasia Suprarrenal Congênita/tratamento farmacológico
Androgênios/secreção
Ritmo Circadiano
Glucocorticoides/administração & dosagem
Hidrocortisona/administração & dosagem
[Mh] Termos MeSH secundário: 17-alfa-Hidroxipregnenolona/urina
Adolescente
Hiperplasia Suprarrenal Congênita/metabolismo
Hiperplasia Suprarrenal Congênita/urina
Adulto
Androsterona/análogos & derivados
Androsterona/urina
Cortodoxona/análogos & derivados
Cortodoxona/urina
Preparações de Ação Retardada
Dexametasona/uso terapêutico
Feminino
Cromatografia Gasosa-Espectrometria de Massas
Glucocorticoides/uso terapêutico
Seres Humanos
Hidrocortisona/uso terapêutico
Masculino
Meia-Idade
Prednisolona/uso terapêutico
Pregnanotriol/análogos & derivados
Pregnanotriol/urina
Adulto Jovem
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Androgens); 0 (Delayed-Action Preparations); 0 (Glucocorticoids); 27178-64-9 (Pregnanetriol); 387-79-1 (17-alpha-Hydroxypregnenolone); 57-61-4 (11 beta-hydroxyandrosterone); 603-99-6 (pregnanetriolone); 68-60-0 (tetrahydro-11-deoxycortisol); 7S5I7G3JQL (Dexamethasone); 9PHQ9Y1OLM (Prednisolone); C24W7J5D5R (Androsterone); WDT5SLP0HQ (Cortodoxone); WI4X0X7BPJ (Hydrocortisone)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170922
[Lr] Data última revisão:
170922
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:161116
[St] Status:MEDLINE
[do] DOI:10.1210/jc.2016-2855


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[PMID]:27835659
[Au] Autor:Bittencourt CR; Izar MC; Schwerz VL; Póvoa RM; Fonseca HA; Fonseca MI; Bianco HT; França CN; Ferreira CE; Fonseca FA
[Ad] Endereço:Cardiology Division, Federal University of Sao Paulo, Sao Paulo, Brazil.
[Ti] Título:Effects of High-Intensity Training of Professional Runners on Myocardial Hypertrophy and Subclinical Atherosclerosis.
[So] Source:PLoS One;11(11):e0166009, 2016.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:To evaluate the effects of long-term exposure to high-intensity training among professional runners on cardiac hypertrophy and subclinical atherosclerosis. Prospective study included runners of both sexes (n = 52) and age and gender matched controls (n = 57), without classical cardiovascular risk factors. Ventricular hypertrophy was quantified by echocardiography by linear method and carotid intima-media thickness (cIMT) by 2-D images obtained by ultrasonography. Endothelial function was evaluated by flow-mediated dilation (FMD). Steroid hormones were quantified by HPLC followed by LC-MS/MS. Higher left ventricular (LV) mass index was found in male athletes (p<0.0001 vs. other groups). When adjusted for gender, the degree of left ventricular mass index classified as mildly, moderately or severely abnormal was obtained in 26%, 35%, and 30%, respectively, of female athletes, and in 39%, 14%, and 21%, respectively, of male athletes. Higher ratio of the early (E) to late (A) ventricular filling velocities was found in athletes of both genders. Male athletes presented lower cIMT in the right (p = 0.012 vs. male controls) and left (p<0.0001 vs. male controls) common carotid arteries, without differences in cIMT between female athletes and controls. FMD results were similar among groups. Higher serum testosterone levels were found in male athletes (p<0.0001 vs. other groups) and they were correlated with LV mass (r = 0.50, p<0.0001). The chronic exposure of high-intensity training among professional runners of both genders was associated with increased ventricular mass and adaptive remodeling. Less subclinical atherosclerosis was found in male athletes. Differences in steroid hormones may account in part for these findings.
[Mh] Termos MeSH primário: Aterosclerose/diagnóstico por imagem
Cardiomegalia/diagnóstico por imagem
Ventrículos do Coração/diagnóstico por imagem
Corrida/fisiologia
[Mh] Termos MeSH secundário: Adulto
Aterosclerose/sangue
Aterosclerose/fisiopatologia
Atletas
Cardiomegalia/sangue
Cardiomegalia/fisiopatologia
Espessura Intima-Media Carotídea
Estudos de Casos e Controles
Corticosterona/sangue
Cortodoxona/sangue
Ecocardiografia
Feminino
Ventrículos do Coração/fisiopatologia
Seres Humanos
Masculino
Resistência Física
Estudos Prospectivos
Testosterona/sangue
Ultrassonografia
Função Ventricular Esquerda
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
3XMK78S47O (Testosterone); W980KJ009P (Corticosterone); WDT5SLP0HQ (Cortodoxone)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170623
[Lr] Data última revisão:
170623
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161112
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0166009


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[PMID]:27416311
[Au] Autor:Hassoun LA; Chahal DS; Sivamani RK; Larsen LN
[Ad] Endereço:School of Medicine, University of California-Davis, Sacramento, California, USA.
[Ti] Título:The use of hormonal agents in the treatment of acne.
[So] Source:Semin Cutan Med Surg;35(2):68-73, 2016 Jun.
[Is] ISSN:1085-5629
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Hormones and androgens play an important role in the pathogenesis of acne. Multiple hormonal modulators are now available for the treatment of acne. The efficacies and side effects of currently available hormonal agents are reviewed here including the use of oral contraceptives, spironolactone, flutamide, cyproterone acetate, finasteride, and cortexolone 17α-propionate. Hormonal therapies are an efficacious treatment option for acne among females. With the growing need to reduce antibiotic exposures, hormonal therapies should be more widely studied and incorporated into acne treatment strategies.
[Mh] Termos MeSH primário: Acne Vulgar/tratamento farmacológico
Anticoncepcionais/uso terapêutico
Fármacos Dermatológicos/uso terapêutico
Hormônios/metabolismo
[Mh] Termos MeSH secundário: Administração Oral
Cortodoxona/análogos & derivados
Cortodoxona/uso terapêutico
Acetato de Ciproterona/uso terapêutico
Feminino
Finasterida/uso terapêutico
Flutamida/uso terapêutico
Hormônios/uso terapêutico
Seres Humanos
Masculino
Metanálise como Assunto
Antagonistas de Receptores de Mineralocorticoides/uso terapêutico
Propionatos/uso terapêutico
Espironolactona/uso terapêutico
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Contraceptive Agents); 0 (Dermatologic Agents); 0 (Hormones); 0 (Mineralocorticoid Receptor Antagonists); 0 (Propionates); 0 (cortexolone 17alpha-propionate); 27O7W4T232 (Spironolactone); 4KM2BN5JHF (Cyproterone Acetate); 57GNO57U7G (Finasteride); 76W6J0943E (Flutamide); WDT5SLP0HQ (Cortodoxone)
[Em] Mês de entrada:1609
[Cu] Atualização por classe:160715
[Lr] Data última revisão:
160715
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160715
[St] Status:MEDLINE
[do] DOI:10.12788/j.sder.2016.027


  8 / 790 MEDLINE  
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[PMID]:27370636
[Au] Autor:Velikanova LI; Shafigullina ZR; Lisitsin AA; Vorokhobina NV; Grigoryan K; Kukhianidze EA; Strelnikova EG; Krivokhizhina NS; Krasnov LM; Fedorov EA; Sablin IV; Moskvin AL; Bessonova EA
[Ad] Endereço:Federal State Budget Institution of Higher Education "North-Western State Medical University named after I.I Mechnikov" under the Ministry of Public Health of the Russian Federation, Saint Petersburg, Russian Federation. velikanovali@hotbox.ru.
[Ti] Título:Different Types of Urinary Steroid Profiling Obtained by High-Performance Liquid Chromatography and Gas Chromatography-Mass Spectrometry in Patients with Adrenocortical Carcinoma.
[So] Source:Horm Cancer;7(5-6):327-335, 2016 Dec.
[Is] ISSN:1868-8500
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Urinary steroid profiling (USP) was studied using high-performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS) methods in 108 patients with adrenocortical adenoma (ACA) and in 31 patients with adrenocortical carcinoma (ACC). Thirteen ACC and Cushing's syndrome (ACC-CS) patients had two types of USP as well as 18 ACC patients without hypercortisolism. These four types differed by androgen and glucocorticoid secretion of the adrenal cortex. Fifteen main ACC features were observed by GC-MS. Urinary excretion of dehydroepiandrosterone (DHEA) was increased in 67.7 % of ACC patients and tetrahydro-11-deoxycortisol (THS) in 74.2 %. By combination of the following parameters: THS >900 µg/24 h and/or DHEA >1500 µg/24 h with ratios of 3α,16,20-pregnentriol/3ß,16,20-pregnentriol (3α,16,20dP3/3ß,16,20dP3) less than 6.0 and 3α,17,20dP3/3ß,17,20dP3 less than 9.0 and the detection of "non-classical" 5-en-pregnens, not found in ACA and healthy persons, 100 % sensitivity and specificity of ACC and ACA differential diagnosis were achieved. Features of 21-hydroxylase and 11ß-hydroxylase deficiency were observed by GC-MS in 32.2 and 61.3 % of the ACC patients, respectively. Additional features for ACC-CS diagnostic were increased urinary excretion of 6ß-hydroxycortisol, 18-hydroxycorticosterone, the sum (UFF + UFE) obtained by HPLC, tetrahydrocorticosterone, and the sum (THF + THE + allo-THF) obtained by GC-MS.
[Mh] Termos MeSH primário: Neoplasias do Córtex Suprarrenal/urina
Adenoma Adrenocortical/urina
Carcinoma Adrenocortical/urina
Cromatografia Líquida de Alta Pressão/métodos
Cromatografia Gasosa-Espectrometria de Massas/métodos
Esteroides/urina
[Mh] Termos MeSH secundário: Neoplasias do Córtex Suprarrenal/diagnóstico
Adenoma Adrenocortical/diagnóstico
Carcinoma Adrenocortical/diagnóstico
Adulto
Cortodoxona/análogos & derivados
Cortodoxona/urina
Síndrome de Cushing/urina
Desidroepiandrosterona/urina
Diagnóstico Diferencial
Feminino
Seres Humanos
Masculino
Meia-Idade
Esteroide 11-beta-Hidroxilase/metabolismo
Esteroide 21-Hidroxilase/metabolismo
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Steroids); 459AG36T1B (Dehydroepiandrosterone); 68-60-0 (tetrahydro-11-deoxycortisol); EC 1.14.14.16 (Steroid 21-Hydroxylase); EC 1.14.15.4 (Steroid 11-beta-Hydroxylase); WDT5SLP0HQ (Cortodoxone)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171110
[Lr] Data última revisão:
171110
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160703
[St] Status:MEDLINE


  9 / 790 MEDLINE  
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[PMID]:27183726
[Au] Autor:Dutov AA; Nikitin DA; Lukyanova YL; Shemiakina NA
[Ti] Título:[THE TECHNIQUE OF HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY FOR SIMULTANEOUS DIAGNOSTIC OF INHERENT HYPERPLASIA OF ADRENAL GLANDS TYPE I AND II].
[So] Source:Klin Lab Diagn;61(1):25-6, 39, 2016 Jan.
[Is] ISSN:0869-2084
[Cp] País de publicação:Russia (Federation)
[La] Idioma:rus
[Ab] Resumo:The article considers the technique of high-performance liquid chromatography making it possible simultaneously detect cortisol, cortisone and secondary steroids in serum for consequent analysis of common reversed-phase high-performance liquid chromatography with ultraviolet under 240 nm. The liquid-liquid extraction from alkaline medium in diethyl ether The separation using column of 150x4.6 size ODS 3.5 mkm in isocratic mode. The eluent acetonitrile--0.02 M phosphate buffer pH 8.0--isopropanol (40:60:1). The application of proposed technique managed to separate cortisol, cortisone, dexamethasone, corticosterone, 11-desoxicortisol, testosterone, desoxicorticosterone, 17α-gidroxiprogesterone and androstendion in 20 minutes. The simplicity, reproducibility and sufficient selectivity and sensitivity of technique permit implement it in clinical practice for simultaneous diagnostic of inherent hyperplasia of adrenal glands type I and II.
[Mh] Termos MeSH primário: Glândulas Suprarrenais/patologia
Cromatografia Líquida de Alta Pressão/métodos
Cortisona/sangue
Hidrocortisona/sangue
[Mh] Termos MeSH secundário: Acetonitrilos/química
Glândulas Suprarrenais/metabolismo
Androstenodiona/sangue
Corticosterona/sangue
Cortodoxona/sangue
Desoxicorticosterona/sangue
Dexametasona/sangue
Seres Humanos
Hidroxiprogesteronas/sangue
Hiperplasia/sangue
Hiperplasia/diagnóstico
Hiperplasia/patologia
Reprodutibilidade dos Testes
Sensibilidade e Especificidade
Testosterona/sangue
[Pt] Tipo de publicação:ENGLISH ABSTRACT; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Acetonitriles); 0 (Hydroxyprogesterones); 312-90-3 (11-hydroxyprogesterone); 3XMK78S47O (Testosterone); 409J2J96VR (Androstenedione); 40GP35YQ49 (Desoxycorticosterone); 7S5I7G3JQL (Dexamethasone); V27W9254FZ (Cortisone); W980KJ009P (Corticosterone); WDT5SLP0HQ (Cortodoxone); WI4X0X7BPJ (Hydrocortisone); Z072SB282N (acetonitrile)
[Em] Mês de entrada:1606
[Cu] Atualização por classe:160517
[Lr] Data última revisão:
160517
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160518
[St] Status:MEDLINE


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Texto completo
[PMID]:27177597
[Au] Autor:Salamanca-Pinzon SG; Khatri Y; Carius Y; Keller L; Müller R; Lancaster CR; Bernhardt R
[Ad] Endereço:Institute of Biochemistry, Saarland University, Saarbrücken, Germany.
[Ti] Título:Structure-function analysis for the hydroxylation of Δ4 C21-steroids by the myxobacterial CYP260B1.
[So] Source:FEBS Lett;590(12):1838-51, 2016 06.
[Is] ISSN:1873-3468
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Myxobacterial CYP260B1 from Sorangium cellulosum was heterologously expressed in Escherichia coli and purified. The in vitro conversion of a small focused substrate library comprised of Δ4 C21-steroids and steroidal drugs using surrogate bovine redox partners shows that CYP260B1 is a novel steroid hydroxylase. CYP260B1 performs the regio- and stereoselective hydroxylation of the glucocorticoid cortodoxone (RSS) to produce 6ß-OH-RSS. The substrate-free crystal structure of CYP260B1 (PDB 5HIW) was resolved. Docking of the tested ligands into the crystal structure suggested that the C17 hydroxy moiety and the presence of either a keto or a hydroxy group at C11 determine the selectivity of hydroxylation.
[Mh] Termos MeSH primário: Proteínas de Bactérias/química
Cortodoxona/química
Myxococcales/enzimologia
Esteroide Hidroxilases/química
[Mh] Termos MeSH secundário: Animais
Proteínas de Bactérias/genética
Proteínas de Bactérias/metabolismo
Bovinos
Cortodoxona/metabolismo
Escherichia coli/genética
Escherichia coli/metabolismo
Hidroxilação
Simulação de Acoplamento Molecular
Myxococcales/genética
Proteínas Recombinantes/química
Proteínas Recombinantes/genética
Esteroide Hidroxilases/genética
Esteroide Hidroxilases/metabolismo
Relação Estrutura-Atividade
[Pt] Tipo de publicação:LETTER; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (Recombinant Proteins); EC 1.14.- (Steroid Hydroxylases); WDT5SLP0HQ (Cortodoxone)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:171126
[Lr] Data última revisão:
171126
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160515
[St] Status:MEDLINE
[do] DOI:10.1002/1873-3468.12217



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