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1.
Artigo em Inglês | MEDLINE | ID: mdl-34201920

RESUMO

Antenatal stress has been associated with adverse birth outcomes such as fetal growth restriction, low birth weight, and preterm birth. Understanding key determinants of stress in a vulnerable pregnant population has the potential of informing development of targeted cost-effective interventions to mitigate against these adverse birth outcomes. We conducted a secondary analysis of data from 150 pregnant women attending antenatal care services at a rural referral hospital in Kenya. The participants completed a sociodemographic and clinical questionnaire, the Cohen's Perceived Stress Scale (PSS) and gave a hair sample for cortisol and cortisone analysis. The association between selected sociodemographic predictors (age, parity, marital status, maternal education, household income, polygyny, and intimate partner violence) and outcomes (hair cortisol, hair cortisone, and PSS score) was examined using univariate, bivariate and multivariate models. We found a negative association between PSS scores and household income (ß = -2.40, p = 0.016, 95% CI = -4.36, -0.45). There was a positive association of the ratio of hair cortisone to cortisol with Adolescent age group (ß = 0.64, p = 0.031, 95% CI = 0.06, 1.22), and a negative association with Cohabitation (ß = -1.21, p = 0.009, 95% CI = -2.11, -0.31). We conclude that household income influenced psychological stress in pregnancy. Adolescence and cohabitation may have an influence on biological stress, but the nature of this effect is unclear.


Assuntos
Cortisona , Nascimento Prematuro , Adolescente , Feminino , Humanos , Hidrocortisona , Recém-Nascido , Quênia/epidemiologia , Paridade , Gravidez , Estresse Psicológico/epidemiologia
2.
J Chromatogr A ; 1652: 462361, 2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-34261023

RESUMO

A modification of magnetic-based solvent-assisted dispersive solid-phase extraction (M-SA-DSPE) has been employed for the determination of the biomarkers cortisol and cortisone in saliva samples. M-SA-DSPE is based on the dispersion of the sorbent material by using a disperser solvent like in dispersive solid phase extraction (SA-DSPE) but a magnetic sorbent is used like in magnetic dispersive solid-phase extraction (M-DSPE). Thus, the magnetic sorbent containing the target analytes is retrieved using an external magnet like in M-DSPE. Finally, the analytes are desorbed into a small volume of organic solvent for the subsequent chromatographic analysis. To this regard, a M-SA-DSPE-based method was developed using a magnetic composite as sorbent, made of CoFe2O4 magnetic nanoparticles embedded into a reversed phase polymer (Strata-XTM-RP), which exhibits affinity to the target analytes. Then, liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) was used to measure both analytes in the M-SA-DSPE extract. Under the optimized conditions, good analytical features were obtained: limits of detection of 0.029 ng mL-1 for cortisol and 0.018 ng mL-1 for cortisone, repeatability (as RSD) ≤ 10 %, and relative recoveries between 86 and 111 %, showing no significant matrix effects. Finally, the proposed method was applied to the analysis of saliva from different volunteers. This new methodology allows a fast and non-invasive determination of cortisol and cortisone, and it employs small amounts of sample, organic solvent and sorbent. Likewise, the sample treatment is minimum, since any supporting equipment (vortex, centrifuge, ultrasounds, etc.) is required.


Assuntos
Cortisona , Hidrocortisona , Saliva , Extração em Fase Sólida , Cromatografia Líquida , Cortisona/análise , Humanos , Hidrocortisona/análise , Fenômenos Magnéticos , Saliva/química , Extração em Fase Sólida/métodos , Solventes/química , Espectrometria de Massas em Tandem
4.
BMC Pediatr ; 21(1): 220, 2021 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-33947355

RESUMO

BACKGROUND: Children with acute peripheral facial nerve palsy cannot yet be recommended corticosteroid treatment based on evidence. Adults with idiopathic facial nerve palsy are treated with corticosteroids, according to guidelines resulting from a meta-analysis comprising two major randomized placebo-controlled trials. Corresponding trials in children are lacking. Furthermore, acute facial nerve palsy in childhood is frequently associated with Lyme neuroborreliosis, caused by the spirochete Borrelia burgdorferi. The efficacy and safety of corticosteroid treatment of acute facial nerve palsy associated with Lyme neuroborreliosis, has not yet been determined in prospective trials in children, nor in adults. METHOD: This randomized double-blind, placebo-controlled study will include a total of 500 Swedish children aged 1-17 years, presenting with acute facial nerve palsy of either idiopathic etiology or associated with Lyme neuroborreliosis. Inclusion is ongoing at 12 pediatric departments, all situated in Borrelia burgdorferi endemic areas. Participants are randomized into active treatment with prednisolone 1 mg/kg/day (maximum 50 mg/day) or placebo for oral intake once daily during 10 days without taper. Cases associated with Lyme neuroborreliosis are treated with antibiotics in addition to the study treatment. The House-Brackmann grading scale and the Sunnybrook facial grading system are used for physician-assessed evaluation of facial impairment at baseline, and at the 1- and 12-month follow-ups. Primary outcome is complete recovery, measured by House-Brackmann grading scale, at the 12-month follow-up. Child/parent-assessed questionnaires are used for evaluation of disease-specific quality of life and facial disability and its correlation to physician-assessed facial impairment will be evaluated. Furthermore, the study will evaluate factors of importance for predicting recovery, as well as the safety profile for short-term prednisolone treatment in children with acute facial nerve palsy. DISCUSSION: This article presents the rationale, design and content of a protocol for a study that will determine the efficacy of corticosteroid treatment in children with acute facial nerve palsy of idiopathic etiology, or associated with Lyme neuroborreliosis. Future results will attribute to evidence-based treatment guidelines applicable also in Borrelia burgdorferi endemic areas. TRIAL REGISTRATION: The study protocol was approved by the Swedish Medical Product Agency (EudraCT nr 2017-004187-35) and published at ClinicalTrials.gov ( NCT03781700 , initial release 12/14/2018).


Assuntos
Borrelia burgdorferi , Cortisona , Neuroborreliose de Lyme , Adolescente , Adulto , Criança , Pré-Escolar , Nervo Facial , Humanos , Lactente , Neuroborreliose de Lyme/complicações , Neuroborreliose de Lyme/diagnóstico , Neuroborreliose de Lyme/tratamento farmacológico , Metanálise como Assunto , Estudos Multicêntricos como Assunto , Estudos Prospectivos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto
5.
Molecules ; 26(5)2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33802594

RESUMO

Cortisone is a steroid widely used as an anti-inflammatory drug able to suppress the immune system, thus reducing inflammation and attendant pain and swelling at the site of an injury. Due to its numerous side effects, especially in prolonged and high-dose therapies, the development of the pharmaceutical industry is currently aimed at finding new compounds with similar activities but with minor or no side effects. Biotransformations are an important methodology towards more sustainable industrial processes, according to the principles of "green chemistry". In this work, the biotransformation of cortisone with Rhodococcus rhodnii DSM 43960 to give two new steroids, i.e., 1,9ß,17,21-tetrahydoxy-4-methyl-19-nor-9ß-pregna-1,3,5(10)-trien-11,20-dione and 1,9ß,17,20ß,21-pentahydoxy-4-methyl-19-nor-9ß-pregna-1,3,5(10)-trien-11-one, is reported. These new steroids have been fully characterized.


Assuntos
Anti-Inflamatórios/síntese química , Anti-Inflamatórios/metabolismo , Cortisona/química , Rhodococcus/química , Esteroides/síntese química , Esteroides/metabolismo , Biotransformação , Química Verde
6.
J Steroid Biochem Mol Biol ; 210: 105874, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33722706

RESUMO

The African clawed frog, Xenopus laevis, is a versatile model for biomedical research and is largely similar to mammals in terms of organ development, anatomy, physiology, and hormonal signaling mechanisms. Steroid hormones control a variety of processes and their levels are regulated by hydroxysteroid dehydrogenases (HSDs). The subfamily of 20ß-HSD type 2 enzymes currently comprises eight members from teleost fish and mammals. Here, we report the identification of three 20ß-HSD type 2 genes in X. tropicalis and X. laevis and the functional characterization of the two homeologs from X. laevis. X. laevis Hsd20b2.L and Hsd20b2.S showed high sequence identity with known 20ß-HSD type 2 enzymes and mapped to the two subgenomes of the allotetraploid frog genome. Both homeologs are expressed during embryonic development and in adult tissues, with strongest signals in liver, kidney, intestine, and skin. After recombinant expression in human cell lines, both enzymes co-localized with the endoplasmic reticulum and catalyzed the conversion of cortisone to 20ß-dihydrocortisone. Both Hsd20b2.L and Hsd20b2.S catalyzed the 20ß-reduction of further C21 steroids (17α-hydroxyprogesterone, progesterone, 11-deoxycortisol, 11-deoxycorticosterone), while only Hsd20b2.S was able to convert corticosterone and cortisol to their 20ß-reduced metabolites. Estrone was only a poor and androstenedione no substrate for both enzymes. Our results demonstrate multispecificity of 20ß-HSD type 2 enzymes from X. laevis similar to other teleost 20ß-HSD type 2 enzymes. X. laevis 20ß-HSD type 2 enzymes are probably involved in steroid catabolism and in the generation of pheromones for intraspecies communication. A role in oocyte maturation is unlikely.


Assuntos
Cortisona Redutase/genética , Cortisona Redutase/metabolismo , Proteínas de Xenopus/genética , Proteínas de Xenopus/metabolismo , Xenopus laevis/genética , 17-alfa-Hidroxiprogesterona/metabolismo , Animais , Cortisona/metabolismo , Embrião não Mamífero , Regulação da Expressão Gênica no Desenvolvimento , Regulação Enzimológica da Expressão Gênica , Células HeLa , Humanos , Filogenia , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Especificidade por Substrato , Xenopus laevis/embriologia
7.
Ann Agric Environ Med ; 28(1): 89-93, 2021 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-33775072

RESUMO

INTRODUCTION: Asthma, a chronic lung disease, is a major health challenge worldwide with increased addressability to health services. There are different asthma phenotypes, which have different evolution and can be specifically tracked. The measurement of fractional expired nitric oxide (FeNo) with different devices reflects the eosinophilic inflammation of the airways, and can be used to evaluate the allergic phenotype and predict the treatment responses. The new GINA (Global Initiative for Asthma) guideline recommends FeNO monitoring to assess adherence to cortisone treatment in high doses before prescribing biological treatment, and as a means of monitoring the decrease in oral corticosteroid treatment. OBJECTIVE: The aim of the study is to analyze the applicability of FeNO in monitoring response to therapy. MATERIAL AND METHODS: An observational study was carried out on 129 subjects with a previously established diagnosis of asthma. The research was based on the determination of FeNO with NObreath. Those with intermediate FeNO received a low dose of inhaled corticosteroids in mono/dual therapy, those with increased FeNO received medium ICS mono/dual therapy. FeNO testing, its values and doses of ICS were below the the ATS / ERS guidelines. RESULTS: FeNO reduction is strictly dependent on the cortisone dose. Applying the dual therapy from the beginning does not bring additional benefits in comparison with cortisone in monotherapy, in terms of FeNO value. CONCLUSIONS: Recommendations that include FeNO testing can help monitor response to treatment.


Assuntos
Asma/terapia , Cortisona/administração & dosagem , Óxido Nítrico/administração & dosagem , Terapia Respiratória , Administração por Inalação , Adulto , Asma/tratamento farmacológico , Asma/imunologia , Terapia Combinada , Feminino , Humanos , Masculino , Adulto Jovem
8.
Ecotoxicol Environ Saf ; 215: 112133, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33740488

RESUMO

BACKGROUND: Although short-term exposure to particulate matter (PM) was associated with increased glucocorticoids (GCs) levels, available evidence on associations of long-term exposure to PM and GCs levels is still scant. Previous studies has showed that meat intake is associated with sex hormones levels, but it is unknown whether meat intake is associated with GCs levels. Furthermore, the role of meat intake in the associations between PM and GCs levels remains unclear. AIMS: The aims of this study were to explore the associations of long-term exposure to PM and GCs levels among Chinese rural adults, and the role of meat intake in these associations. MATERIALS AND METHODS: A total of 6223 subjects were recruited from the Henan Rural Cohort Study. Serum GCs levels were measured with liquid chromatography-tandem mass spectrometry. The concentrations of PM (PM1 and PM2.5) for each subject were assessed with machine learning algorithms. The food frequency questionnaire (FFQ) was used to obtain each participant' information on meat intake. The effects of PM and meat intake on GCs levels were assessed using generalized linear models. In addition, modification analyses were performed to identify the role of meat intake played in the associations of PM with serum GCs levels. RESULTS: Per 1 µg/m3 increment in PM1 or PM2.5 concentration was associated with a 0.364 ng/ml (95% confidence interval (CI): 0.234, 0.494) or 0.227 ng/ml (95%CI: 0.110, 0.343) increase in serum cortisone, respectively. In addition, the moderation effects of total meat intake and red meat intake on the associations of long-term exposure to PM1 or PM2.5 with serum cortisone were observed (P < 0.05), indicating that individuals who had high levels of PM1 or PM2.5 and meat intake were more susceptible to have a higher state of serum cortisone. CONCLUSIONS: Our findings suggested that long-term exposure to PM1 or PM2.5 was associated with serum cortisone. Moreover, meat intake was found to be a significant moderator in the association of PM1 or PM2.5 with serum cortisone levels.


Assuntos
Poluição do Ar/estatística & dados numéricos , Cortisona/sangue , Dieta/estatística & dados numéricos , Exposição Ambiental/estatística & dados numéricos , Carne/estatística & dados numéricos , Material Particulado/análise , Adulto , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Grupo com Ancestrais do Continente Asiático , Estudos de Coortes , Cortisona/análise , Exposição Ambiental/análise , Feminino , Humanos , Modelos Lineares , Masculino , Carne/análise , Pessoa de Meia-Idade , População Rural
10.
J Steroid Biochem Mol Biol ; 210: 105850, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33639236

RESUMO

11ß-Hydroxysteroid dehydrogenase 1 (11ß-HSD1) plays an important role in pre-receptor glucocorticoid metabolism. This enzyme is expressed in bone, increases with age, and catalyzes the conversion of the inactive glucocorticoid cortisone into the active glucocorticoid cortisol and vice versa. Here we hypothesized that the physiological activity of 11ß-HSD1 to produce cortisol in human mesenchymal progenitor cells (hMSC) is principally sufficient to shift the differentiation potential in the direction of adipogenic. We thus investigated differentiating hMSCs and the mesenchymal stem cell line SCP-1 cultured under osteogenic conditions and stimulated with supra-physiological cortisone levels. The release of active cortisol into the medium was monitored and the influence on cell differentiation analyzed. We revealed an increase in 11ß-HSD1 expression followed by increased reductive activity of the enzyme, thereby inducing a more adipogenic phenotype of the cell models via cortisol with negative effects on osteogenesis. Through inhibition experiments with the specific inhibitor 10 j, we proved the enzyme specificity for cortisol synthesis and adipogenic differentiation. Increased expression of 11ß-HSD1 followed by higher cortisol levels might thus explain bone marrow adiposity followed by reduced bone quality and stability in old age or in situations of supra-physiological glucocorticoid exposure.


Assuntos
11-beta-Hidroxiesteroide Desidrogenase Tipo 1/metabolismo , Adipogenia , Hidrocortisona/biossíntese , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Osteogênese , 11-beta-Hidroxiesteroide Desidrogenase Tipo 1/antagonistas & inibidores , 11-beta-Hidroxiesteroide Desidrogenase Tipo 1/genética , Adipogenia/fisiologia , Diferenciação Celular/fisiologia , Células Cultivadas , Cromatografia Líquida , Cortisona/metabolismo , Cortisona/farmacologia , Inibidores Enzimáticos/farmacologia , Regulação Enzimológica da Expressão Gênica , Humanos , Hidrocortisona/farmacologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Osteoblastos/citologia , Osteoblastos/metabolismo , Osteogênese/fisiologia , Espectrometria de Massas em Tandem
11.
Molecules ; 26(2)2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-33478156

RESUMO

Long-term dependence of illicit drugs impairs the function of the hypothalamic-pituitary-adrenal (HPA) axis, which regulates the secretion of endogenous steroids, cortisol, and cortisone. Thus, the present study aimed to develop a sensitive method for simultaneous determination of the multiple illicit drugs and two steroids in hair to monitor the status of illicit drug exposure and the physiological and psychological health of drug addicts. The target analytes were extracted from hair by incubation with 1 mL methanol for 24 h at 40 °C and then determined with LC-APCI+-MS/MS. The validated method showed acceptable linearity (R 2 > 0.99) in the range of 1.25-250 pg/mg for cortisol and cortisone, 2.5-125 pg/mg for heroin, 2.5-1250 pg/mg for ketamine, 2.5-5000 pg/mg for methamphetamine (MAM), 2.5-250 pg/mg for 3, 4-methylenedioxymethamphetamine (MDMA), morphine, and 6-monoacetylmorphine (6-AM). Limits of quantification were 1.6, 1.2, 1.6, 1.0, 1.4, 0.3, 2.1, and 1.2 pg/mg for cortisol, cortisone, heroin, ketamine, MAM, MDMA, morphine, and 6-AM, respectively. Method recoveries were from 90-115% for all analytes. Inter-day and intra-day coefficients of variation were within 10%. Finally, this method was successfully applied to detect the aforementioned analytes in hair among female drug addicts who self-reported to be MAM abuser, heroin abuser, ketamine abuser, and abuser of mixture drugs of MAM and heroin. MAM abusers with current MAM use showed significantly higher concentrations of cortisol, MAM, and MDMA than controls with drug withdrawal.


Assuntos
Cromatografia Líquida , Cortisona/análise , Cabelo/química , Hidrocortisona/análise , Drogas Ilícitas/análise , Espectrometria de Massas em Tandem , Feminino , Humanos , Limite de Detecção
12.
Eur J Endocrinol ; 184(3): 445-454, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33449913

RESUMO

Objective: Hair cortisol (HF) and cortisone (HE) measurements reflect tissular exposure to cortisol over months and are increased in overt Cushing's syndrome (CS). No data is available in mild CS. We compared the diagnostic performance of HF and HE between patients with overt or mild CS. Design: Single centre retrospective study. Methods: HF&HE were measured by LC-MS/MS in 48 consecutive adult females with Cushing's disease (CD), ectopic ACTH syndrome, secreting adenomas and carcinomas, and adrenal incidentalomas. All had impaired dexamethasone suppression tests. Overt CS (n = 25) was diagnosed in front of specific symptoms, a mean UFC (>1.5 ULN) and increased midnight serum cortisol or salivary cortisol. Mild CS (n = 23) was diagnosed in patients lacking specific symptoms and displaying at least one additional biological abnormality including mildly increased UFC (≤1.5 ULN), increased midnight serum cortisol or salivary cortisol and suppressed plasma ACTH in patients with adrenal tumours. In this study, 84 healthy subjects and obese patients served as controls. Results: HF and HE showed roughly similar performance in overt CS (92 and 100% sensitivity, 91 and 99% specificity, respectively). HF and HE were lower in mild CS but higher than in controls (P < 0.01). HE was correlated with midnight serum cortisol (P < 0.02) and volume of adrenal incidentalomas (P < 0.04) but not with UFC. HF and HE had 59% and 68% sensitivity, and 79 and 94% specificity, respectively, for the diagnosis of mild CS. Contrary to UFC, both HF and HE were in the range of overt CS in 11/23 patients with mild CS. Patients with mild CS and increased HE required more antihypertensive treatments and showed worser lipid profiles than patients with normal HE. Conclusions: HF and HE measurement performed better in overt than in mild CS but is a useful adjunct to diagnose mild CS and to identify adrenocortical incidentalomas responsible for excessive cortisol exposure.


Assuntos
Cortisona/análise , Síndrome de Cushing/diagnóstico , Técnicas de Diagnóstico Endócrino , Cabelo/química , Hidrocortisona/análise , Síndrome de ACTH Ectópico/diagnóstico , Síndrome de ACTH Ectópico/metabolismo , Adenoma/diagnóstico , Adenoma/metabolismo , Neoplasias das Glândulas Suprarrenais/diagnóstico , Neoplasias das Glândulas Suprarrenais/metabolismo , Adulto , Idoso , Estudos de Casos e Controles , Cortisona/metabolismo , Síndrome de Cushing/metabolismo , Síndrome de Cushing/patologia , Feminino , Cabelo/metabolismo , Humanos , Hidrocortisona/metabolismo , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Índice de Gravidade de Doença
13.
Endocrine ; 73(1): 177-185, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33417142

RESUMO

PURPOSE: Conventional (CONV) treatment of adrenal insufficiency (AI) is associated with risk of overtreatment: glyco-metabolic impairment, bone loss, and reduced quality of life. Recent findings suggest that modified-release hydrocortisone (MOD) may restore a more physiological cortisol profile. Our aims were: (1) to compare the gene expression profile of peripheral blood mononuclear cells derived from patients, with secondary AI (SAI), under CONV (cortisone acetate or hydrocortisone) or MOD versus healthy controls; and (2) to evaluate MOD effects on serum cortisol profile, glucose, lipid, bone, and clinical parameters. METHODS: Thirteen patients with SAI were switched from CONV to MOD at equivalent dose. Area under curve (AUC) of both formulations was calculated in six patients. Clinical, metabolic and bone parameters were measured at baseline and 3 months after MOD in all patients. In six patients and six age- and sex-matched healthy controls, a whole-genome expression analysis was performed at baseline, 1 month, and 3 months after MOD. RESULTS: (1) The number of genes differentially expressed (n = 235; mainly involved in immune response and metabolism) in SAI patients compared to controls progressively and significantly decreased switching from CONV to MOD (n = 78 at 3 months). (2) Under MOD: AUC of cortisol exposure tended to be smaller and cortisol levels showed a more physiological profile; no significant changes of clinical, metabolic and bone parameters were observed, likely due to the short follow-up, but triglycerides tended slightly to increase. CONCLUSIONS: MOD may restore a normal gene expression profile as soon as 1 month after switching from CONV.


Assuntos
Insuficiência Adrenal , Cortisona , Insuficiência Adrenal/tratamento farmacológico , Insuficiência Adrenal/genética , Humanos , Hidrocortisona , Leucócitos Mononucleares , Qualidade de Vida
14.
Arch Gynecol Obstet ; 303(2): 401-408, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32880710

RESUMO

PURPOSE: Labor is a complex process involving multiple para-, auto- and endocrine cascades. The interaction of cortisol, corticotropin-releasing hormone (CRH) and progesterone is essential. The action of cortisol on the human feto-placental unit is regulated by 11beta-hydroxysteroid dehydrogenase type 2 (11ß-HSD2/HSD11B2) that converts cortisol into inactive cortisone. The majority of studies on the assessment of placental 11ß-HSD2 function determined indirect activity parameters. It remains elusive if indirect measurements correlate with enzymatic function and if these parameters are affected by potential confounders (e.g., mode of delivery). Thus, we compared determinants of indirect 11ß-HSD2 tissue activity with its direct enzymatic turnover rate in placental samples from spontaneous births and cesarean (C)-sections. METHODS: Using LC-MS/MS, we determined CRH, cortisol, cortisone, progesterone and 17-hydroxy(OH)-progesterone in human term placentas (spontaneous birth vs. C-section, n = 5 each) and measured the enzymatic glucocorticoid conversion rates in placental microsomes. Expression of HSD11B1, 2 and CRH was determined via qRT-PCR in the same samples. RESULTS: Cortisol-cortisone ratio correlated with direct microsomal enzymatic turnover. While this observation seemed independent of sampling site, a strong influence of mode of delivery on tissue steroids was observed. The mRNA expression of HSD11B2 correlated with indirect and direct cortisol turnover rates in C-section placentas only. In contrast to C-sections, CRH, cortisol and cortisone levels were significantly increased in placental samples following spontaneous birth. CONCLUSION: Labor involves a series of complex hormonal processes including activation of placental CRH and glucocorticoid metabolism. This has to be taken into account when selecting human cohorts for comparative analysis of placental steroids.


Assuntos
11-beta-Hidroxiesteroide Desidrogenase Tipo 2/metabolismo , Hormônio Liberador da Corticotropina/metabolismo , Glucocorticoides/metabolismo , Hidrocortisona/metabolismo , Trabalho de Parto , Placenta/enzimologia , 11-beta-Hidroxiesteroide Desidrogenase Tipo 2/genética , Adulto , Cromatografia Líquida , Cortisona/metabolismo , Feminino , Expressão Gênica , Humanos , Placenta/metabolismo , Gravidez , Progesterona/metabolismo , RNA Mensageiro , Espectrometria de Massas em Tandem
15.
Ir J Med Sci ; 190(2): 615-623, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-32803648

RESUMO

BACKGROUND: Measurement of late night salivary cortisol (LNSF) is useful in the identification of cyclical Cushing's syndrome (CS); the usefulness of its metabolite cortisone (late night salivary cortisone, LNSE) is less well described. AIM: The aim of this study was to determine the utility of measuring LNSE in patients with confirmed CS compared with other diagnostic tests and to analyse serial LNSF measurements for evidence of variable hormonogenesis. METHODS: This was a retrospective observational study including patients with confirmed CS in whom LNSF and LNSE were measured. RESULTS: Twenty-three patients with confirmed CS were included, 21 with Cushing's disease. LNSF had a sensitivity of 92%, LNSE 87% and combined LNSF/LNSE 94% per sample. Four patients had cyclical hormonogenesis, when the definition of one trough and two peaks was applied to LNSF measurements, and a fifth patient fell just outside the criteria. Six patients had evidence of variable hormonogenesis, defined as doubling of LNSF concentration on serial measurements. Sensitivity of 24-h urinary free cortisol (UFC) was 89% per collection. Sixteen patients had simultaneous measurements of LNSF and UFC; in three patients, they provided discordant results. CONCLUSION: LNSF appears more sensitive than LNSE and UFC in the diagnosis of CS, combining LNSF and LNSE results leads to superior sensitivity. Half of our cohort had evidence of cyclical or variable hormonogenesis. Fluctuations in LNSF did not always correlate with changes in UFC concentration, emphasising the importance of performing more than one screening test, particularly if pretest clinical suspicion is high.


Assuntos
Ritmo Circadiano/fisiologia , Cortisona/metabolismo , Síndrome de Cushing/diagnóstico , Hidrocortisona/metabolismo , Saliva/química , Adolescente , Adulto , Idoso , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
16.
Arthroscopy ; 36(12): 2973-2974, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33276885

RESUMO

Snapping scapula syndrome and scapulothoracic bursitis are rare, often painful or functionally limiting conditions that can present owing to underlying anatomic abnormalities or can be idiopathic in nature. When there are no underlying structural abnormalities, diagnosis can be challenging and frequently patients will present with chronic pain having received multiple diagnostic and treatment modalities with no success. Injections into the scapulothoracic bursa, in conjunction with physical therapy, have been shown to be effective for the patient with snapping scapula syndrome and/or scapulothoracic bursitis, when recognized. Yet, some cases are recalcitrant to conservative treatment, and surgical intervention is required. As with any procedure, patient selection for surgical intervention is critical and based on the diagnostic workup-particularly, the response to diagnostic or therapeutic injections. The best surgical outcomes may be achieved in patients who receive bursectomy in conjunction with partial scapulectomy, and negative prognostic factors include older age, lower preoperative psychological score, and longer duration of symptoms.


Assuntos
Bursite , Cortisona , Idoso , Bursite/diagnóstico , Bursite/cirurgia , Humanos , Prognóstico , Escápula/cirurgia , Ultrassonografia de Intervenção
17.
Int J Mol Sci ; 21(23)2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33255713

RESUMO

Macrophages are crucial not only for initiation of inflammation and pathogen eradication (classically polarized M1 macrophages), but also for inflammation inhibition and tissue regeneration (alternatively polarized M2 macrophages). Their polarization toward the M1 population occurs under the influence of interferon-γ + lipopolysaccharide (IFN-γ + LPS), while alternatively polarized M2 macrophages evolve upon, e.g., interlukin 4 (IL-4) or cortisol stimulation. This in vitro study focused on a possible role for macrophage-derived cortisol in M1/M2 polarization in common carp. We studied the expression of molecules involved in cortisol synthesis/conversion from and to cortisone like 11ß-hydroxysteroid dehydrogenase type 2 and 3. (11ß-HSD2 and 3) and 11ß-hydroxylase (CYP11b), as well as the expression of glucocorticoid receptors (GRs) and proliferator-activated receptor gamma (PPARγ) in M1 and M2 macrophages. Lastly, we analyzed how inhibition of these molecules affect macrophage polarization. In M1 cells, upregulation of gene expression of GRs and 11ß-HSD3 was found, while, in M2 macrophages, expression of 11ß-hsd2 was upregulated. Moreover, blocking of cortisol synthesis/conversion and GRs or PPARγ induced changes in expression of anti-inflammatory interleukin 10 (IL-10). Consequently, our data show that carp monocytes/macrophages can convert cortisol. The results strongly suggest that cortisol, via intracrine interaction with GRs, is important for IL-10-dependent control of the activity of macrophages and for the regulation of M1/M2 polarization to finally determine the outcome of an infection.


Assuntos
Carpas/metabolismo , Hidrocortisona/metabolismo , Infecções/genética , Inflamação/genética , Macrófagos/metabolismo , Animais , Carpas/genética , Diferenciação Celular/genética , Polaridade Celular/genética , Cortisona/genética , Cortisona/metabolismo , Infecções/microbiologia , Inflamação/metabolismo , Inflamação/patologia , Interferon gama/genética , Metabolismo dos Lipídeos/genética , Lipopolissacarídeos/metabolismo , Ativação de Macrófagos/genética
18.
J Laryngol Otol ; 134(12): 1123-1127, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33190655

RESUMO

BACKGROUND: Olfactory dysfunction represents one of the most frequent symptoms of coronavirus disease 2019, affecting about 70 per cent of patients. However, the pathogenesis of the olfactory dysfunction in coronavirus disease 2019 has not yet been elucidated. CASE REPORT: This report presents the radiological and histopathological findings of a patient who presented with anosmia persisting for more than three months after infection with severe acute respiratory syndrome coronavirus-2. CONCLUSION: The biopsy demonstrated significant disruption of the olfactory epithelium. This shifts the focus away from invasion of the olfactory bulb and encourages further studies of treatments targeted at the surface epithelium.


Assuntos
Anosmia/etiologia , COVID-19/complicações , Transtornos do Olfato/fisiopatologia , Mucosa Olfatória/patologia , Anosmia/diagnóstico , Anosmia/tratamento farmacológico , Anosmia/virologia , COVID-19/diagnóstico , COVID-19/epidemiologia , COVID-19/virologia , Cortisona/administração & dosagem , Cortisona/uso terapêutico , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Pessoa de Meia-Idade , Bulbo Olfatório/diagnóstico por imagem , Mucosa Olfatória/virologia , SARS-CoV-2/genética , Resultado do Tratamento
19.
Eur J Endocrinol ; 183(6): 669-676, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33112256

RESUMO

Context: Obesity and cardiometabolic diseases are associated with higher long-term glucocorticoid levels, measured as scalp hair cortisol (HairF) and cortisone (HairE). Cardiometabolic diseases have also been associated with copeptin, a stable surrogate marker for the arginine-vasopressin (AVP) system. Since AVP is, together with corticotropin-releasing hormone (CRH) an important regulator of the hypothalamic-pituitary adrenal axis (HPA axis), we hypothesize that AVP contributes to chronic hypercortisolism in obesity. Objective: To investigate whether copeptin levels are associated with Higher HairF and HairE levels in obesity. Design: A cross-sectional study in 51 adults with obesity (BMI ≥30 kg/m2). Methods: Associations and interactions between copeptin, HairF, HairE, and cardiometabolic parameters were cross-sectionally analyzed. Results: Copeptin was strongly associated with BMI and waist circumference (WC) (rho = 0.364 and 0.530, P = 0.008 and <0.001, respectively), also after correction for confounders. There were no associations between copeptin and HairF or HairE on a continuous or dichotomized scale, despite correction for confounders. Conclusion: In patients with obesity, AVP seems not a major contributor to the frequently observed high cortisol levels. Other factors which stimulate the HPA axis or affect cortisol synthesis or breakdown may be more important than the influence of AVP on long-term glucocorticoid levels in obesity.


Assuntos
Cortisona/metabolismo , Síndrome de Cushing/etiologia , Glicopeptídeos/metabolismo , Hidrocortisona/metabolismo , Obesidade/metabolismo , Adulto , Arginina Vasopressina/metabolismo , Biomarcadores/metabolismo , Índice de Massa Corporal , Hormônio Liberador da Corticotropina/metabolismo , Estudos Transversais , Feminino , Glucocorticoides/metabolismo , Cabelo/química , Humanos , Sistema Hipotálamo-Hipofisário/metabolismo , Masculino , Obesidade/complicações , Sistema Hipófise-Suprarrenal/metabolismo
20.
Arthroscopy ; 36(12): 2965-2972, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32888981

RESUMO

PURPOSE: To evaluate the prognostic value of an ultrasound-guided subscapular local anesthetic and cortisone injection in a consecutive series of patients who underwent an arthroscopic superior medial scapuloplasty for snapping scapula syndrome (SSS) and had been refractory to conservative treatment. METHODS: We undertook an arthroscopic superior medial scapuloplasty on patients with a clinical diagnosis of SSS who had failed a structured physiotherapy program and had either gained a good response or no to minimal response to preoperative ultrasound-guided subscapular local anesthetic and cortisone injection. The patients were assessed preoperatively and at final follow-up with the QuickDASH and Constant scores, and their pain was assessed with a visual analog scale (VAS). RESULTS: Between January 2009 and December 2016, 47 patients were included in the study, with a minimal follow-up of 2 years. There were 29 female and 18 male patients, and the mean age at the time of surgery was 27.4 years (range 15 to 61). Forty-two patients were available at final follow-up. There were 31 patients in the good response group and 11 patients in the no to minimal response group. For all patients, the mean time to follow-up was 41.8 months (range 24 to 108). There was a significant improvement after surgery in the mean QuickDASH score (from 39 to 20, P < .001) (minimal clinically important difference [MCID] 15.91) , Constant score (from 57 to 87, P < .001) (MCID 10.4), and VAS (from 6 to 2, P < .001) (MCID 3). For the good response group, there was a significant improvement after surgery in the mean QuickDASH score (from 38 to 18, P < .001) (MCID 15.91), the Constant score (from 57 to 89) (MCID 10.4), and the VAS (from 6 to 2, P < .001) (MCID 3). For the no to minimal response group, there was a significant improvement after surgery in the mean QuickDASH score (from 42 to 24, P < .01) (MCID 15.91), the Constant score (from 58 to 80, P < .002) (MCID 10.4), and the VAS (from 6 to 2, P < .01) (MCID 3). The difference in postoperative improvement of the QuickDASH and Constant scores between the good response and the no to minimal response groups was statistically significant (P < .05). CONCLUSION: The results of this study suggest that arthroscopic scapuloplasty can lead to a significant improvement in pain and function in all patients with a clinical diagnosis of snapping scapula syndrome refractory to conservative treatment. Patients who gained a good transient response to a preoperative ultrasound-guided subscapular cortisone injection obtained a significantly better recovery than those who did not. A preoperative ultrasound-guided subscapular cortisone injection appeared to be of prognostic value.


Assuntos
Artroscopia/métodos , Cortisona/administração & dosagem , Escápula/cirurgia , Ultrassonografia de Intervenção , Adolescente , Adulto , Feminino , Humanos , Injeções , Masculino , Pessoa de Meia-Idade , Diferença Mínima Clinicamente Importante , Medição da Dor , Período Pós-Operatório , Prognóstico , Resultado do Tratamento , Ultrassonografia , Escala Visual Analógica , Adulto Jovem
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