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1.
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
2.
Nat Commun ; 11(1): 5386, 2020 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-33106488

RESUMO

Stress-related disorders such as depression and anxiety are characterized by enhanced negative emotion and physiological dysfunction. Whilst elevated activity within area 25 of the subgenual anterior cingulate cortex (sgACC/25) has been implicated in these illnesses, it is unknown whether this over-activity is causal. By combining targeted intracerebral microinfusions with cardiovascular and behavioral monitoring in marmosets, we show that over-activation of sgACC/25 reduces vagal tone and heart rate variability, alters cortisol dynamics during stress and heightens reactivity to proximal and distal threat. 18F-FDG PET imaging shows these changes are accompanied by altered activity within a network of brain regions including the amygdala, hypothalamus and dorsolateral prefrontal cortex. Ketamine, shown to have rapid antidepressant effects, fails to reverse elevated arousal to distal threat contrary to the beneficial effects we have previously demonstrated on over-activation induced reward blunting, illustrating the symptom-specificity of its actions.


Assuntos
Vias Autônomas/fisiologia , Callithrix/psicologia , Fenômenos Fisiológicos Cardiovasculares , Giro do Cíngulo/fisiologia , Animais , Nível de Alerta , Comportamento Animal , Callithrix/fisiologia , Medo , Feminino , Giro do Cíngulo/diagnóstico por imagem , Frequência Cardíaca , Hidrocortisona/metabolismo , Masculino , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons
3.
Radiol Clin North Am ; 58(6): 1099-1113, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33040851

RESUMO

Endocrine disorders associated with adrenal pathologies can be caused by insufficient adrenal gland function or excess hormone secretion. Excess hormone secretion may result from adrenal hyperplasia or hormone-secreting (ie, functioning) adrenal masses. Based on the hormone type, functioning adrenal masses can be classified as cortisol-producing tumors, aldosterone producing tumors, and androgen-producing tumors, which originate in the adrenal cortex, as well as catecholamine-producing pheochromocytomas, which originate in the medulla. Nonfunctioning lesions can cause adrenal gland enlargement without causing hormonal imbalance. Evaluation of adrenal-related endocrine disorders requires clinical and biochemical workup associated with imaging evaluation to reach a diagnosis and guide management.


Assuntos
Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Síndrome de Cushing/diagnóstico por imagem , Doenças do Sistema Endócrino/diagnóstico por imagem , Feocromocitoma/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Neoplasias das Glândulas Suprarrenais/patologia , Neoplasias das Glândulas Suprarrenais/cirurgia , Glândulas Suprarrenais/diagnóstico por imagem , Glândulas Suprarrenais/metabolismo , Glândulas Suprarrenais/patologia , Adrenalectomia/métodos , Aldosterona/metabolismo , Androgênios/metabolismo , Síndrome de Cushing/patologia , Doenças do Sistema Endócrino/fisiopatologia , Feminino , Humanos , Hidrocortisona/metabolismo , Masculino , Feocromocitoma/patologia , Prognóstico , Índice de Gravidade de Doença
4.
Ecotoxicol Environ Saf ; 203: 111014, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32888589

RESUMO

Tributyltin (TBT), a widely and persistently distributed organontin, has been well documented to disrupt reproduction and behaviors in animals due to its anti-aromatase activity. TBT has been also reported to enhance anxiety in several fish species, whereas the mechanism underlying remains largely unknown. To investigate the disruption of TBT on fish anxiety and the mechanisms possibly involved, adult male zebrafish (Danio rerio) were treated with TBT (100 and 500 ng/L) for 28 days and anxiety behavior was further investigated using a novel tank dive test. Result showed that TBT treatment significantly enhanced the total time of the fish spent in the lower half, delayed the onset time to the higher half of the tank and increased the total duration of freezing of the fish, indicating an enhanced anxiety in TBT-treated fish. Accordingly, TBT sharply elevated the cortisol levels in plasma in a concentration-dependent manner, suggesting that the elevated cortisol level might be involved in the enhanced anxiety. Although the expression of crha was significantly increased and crhbp was significantly decreased in the brain of TBT-treated fish which is consistent to the elevated cortisol level, the expressions of actha and acthb were sharply down-regulated. In contrast, the expressions of genes responsible for the synthesis and action of serotonin (5-HT) (pet1, thp2 and htr1aa), dopamine (DA) (th1, slc6a3, drd2a and drd2b) and gamma-aminobutyric acid (GABA) (gad2 and gabrg2) were all significantly inhibited. The down-regulation of these pivotal genes acting in 5-HT, DA and GABA neurotransmitter systems in response to TBT corresponded well with the TBT-enhanced anxiety in fish. It was thus strongly suggested that these neurotransmitters might be also involved in TBT-enhanced anxiety in adult male zebrafish. The present study extended our understanding of the neurotoxicity of TBT on the anxiety control and behavioral modulation in fish.


Assuntos
Ansiedade/induzido quimicamente , Hidrocortisona/metabolismo , Neurotransmissores/metabolismo , Compostos de Trialquitina/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Dopamina/metabolismo , Masculino , Serotonina/metabolismo , Transdução de Sinais/efeitos dos fármacos , Peixe-Zebra/metabolismo , Ácido gama-Aminobutírico/metabolismo
5.
Chemosphere ; 260: 127565, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32758781

RESUMO

The effects of fluoride on endocrine tissues has not been sufficiently explored to date. The current body of knowledge suggest significant effects of that mineral on reducing sex hormone levels, which may consequently impair fertility and disrupt puberty. The majority of studies confirm that sodium fluoride increases TSH levels and decreases the concentrations of T3 and T4 produced by the thyroid. Moreover, a correlation was observed between NaF and increased secretion of PTH by the parathyroid glands, without a significant impact on body calcium levels. Probably, fluoride may exert adverse effects on insulin levels, impairing pancreatic function and resulting in abnormal glucose tolerance. Observations also include decreased levels of cortisol secreted by the adrenal glands. In light of the few existing studies, the mechanism of fluoride toxicity on the endocrine system has been described.


Assuntos
Sistema Endócrino/efeitos dos fármacos , Fluoretos/farmacologia , Glândulas Suprarrenais/metabolismo , Animais , Fluoretos/efeitos adversos , Fluoretos/toxicidade , Humanos , Hidrocortisona/metabolismo , Insulina/análise , Glândulas Paratireoides/efeitos dos fármacos , Glândulas Paratireoides/metabolismo , Fluoreto de Sódio/farmacologia , Fluoreto de Sódio/toxicidade , Glândula Tireoide/efeitos dos fármacos , Glândula Tireoide/metabolismo , Hormônios Tireóideos/metabolismo
6.
PLoS One ; 15(8): e0236669, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32750092

RESUMO

This study examined the effect of a competitive season on salivary responses [cortisol (sC), testosterone (sT), Testosterone/Cortisol ratio (sT/C), Immunoglobulin A (sIgA), sIgA secretion rate (srIgA), alpha-amylase (sAA)] and upper respiratory symptoms (URS) occurrence in three teams of male soccer players (Under-15, Under-17 and Under-19 yrs.). Training and competition volumes, salivary biomarkers and URS were determined monthly. No differences were found for monthly training volume between teams. Incidence of URS was higher for the U15 (44.9% of the total cases). Higher sT and srIgA were observed for the U19, lower sC were found for the U17 and sAA showed higher values for the U15 throughout the season. In the U15, significant difference (p = .023) was found for sIgA concentration with higher concentration values in January compared to December (-42.7%; p = .008) and the sT showed seasonal variation (p < .001) with the highest value in January significantly different from October (-40.2%; p = .035), November (-38.5%; p = 0.022) and December (-51.6%; p = .008). The U19 presented an increase in sC in March compared to February (-66.1%, p = .018), sT/C were higher in February compared to March (-58.1%; p = .022) and sAA increased in March compared to September (-20.5%; p = .037). Negative correlations, controlled for age group, were found between URS occurrence and srIgA (r = -0.170, p = .001), sAA (r = -0.179, p = .001) and sT (r = -0.107, p = .047). Monitoring salivary biomarkers provides information on mucosal immunity with impact in URS occurrence. Coaches could manipulate training loads to attenuate the physical stressors imposed on athletes, especially at demanding and stressful periods.


Assuntos
Atletas , Imunidade nas Mucosas , Doenças Respiratórias/imunologia , Saliva/imunologia , Futebol , Adolescente , Biomarcadores/metabolismo , Humanos , Hidrocortisona/metabolismo , Imunoglobulina A Secretora/metabolismo , Masculino , Estações do Ano , Testosterona/metabolismo , alfa-Amilases/metabolismo
7.
J Steroid Biochem Mol Biol ; 202: 105730, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32682944

RESUMO

Deficiency in Sphingosine-1-phosphate lyase (S1P lyase) is associated with a multi-systemic disorder incorporating primary adrenal insufficiency (PAI), steroid resistant nephrotic syndrome and neurological dysfunction. Accumulation of sphingolipid intermediates, as seen with loss of function mutations in SGPL1, has been implicated in mitochondrial dysregulation, including alterations in mitochondrial membrane potentials and initiation of mitochondrial apoptosis. For the first time, we investigate the impact of S1P lyase deficiency on mitochondrial morphology and function using patient-derived human dermal fibroblasts and CRISPR engineered SGPL1-knockout HeLa cells. Reduced cortisol output in response to progesterone stimulation was observed in two patient dermal fibroblast cell lines. Mass spectrometric analysis of patient dermal fibroblasts revealed significantly elevated levels of sphingosine-1-phosphate, sphingosine, ceramide species and sphingomyelin when compared to control. Total mitochondrial volume was reduced in both S1P lyase deficient patient and HeLa cell lines. Mitochondrial dynamics and parameters of oxidative phosphorylation were altered when compared to matched controls, though differentially across the cell lines. Mitochondrial dysfunction may represent a major event in the pathogenesis of this disease, associated with severity of phenotype.


Assuntos
Insuficiência Adrenal/metabolismo , Aldeído Liases/deficiência , Mitocôndrias/metabolismo , Doenças Mitocondriais/metabolismo , Insuficiência Adrenal/genética , Aldeído Liases/genética , Respiração Celular , Células Cultivadas , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Humanos , Hidrocortisona/metabolismo , Doenças Mitocondriais/genética , Fosfoproteínas/genética , Progesterona/farmacologia , Pele/citologia
8.
Lancet Diabetes Endocrinol ; 8(9): 748-761, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32730798

RESUMO

BACKGROUND: Cushing's disease is a rare endocrine disorder characterised by cortisol overproduction with severe complications. Therapies for cortisol reduction are often necessary. Here we report the outcomes from the pivotal phase III study of osilodrostat (a potent oral inhibitor of cytochrome P450 11B1, mitochondrial [11ß-hydroxylase]; Novartis Pharma AG, Basel, Switzerland) in patients with Cushing's disease. METHODS: LINC 3 was a prospective, multicentre, open-label, phase III study with a double-blind randomised withdrawal period, that comprised four periods. Patients aged 18-75 years, with confirmed persistent or recurrent Cushing's disease (defined as mean 24-h urinary free cortisol [UFC] concentration >1·5 times the upper limit of normal [ULN] and morning plasma adrenocorticotropic hormone above the lower limit of normal) who had previously had pituitary surgery or irradiation, or were newly diagnosed and who refused surgery or were not surgical candidates, were recruited from 66 hospital sites and private clinical practices in 19 countries. In period 1, open-label osilodrostat was initiated in all participants and adjusted every 2 weeks (1-30 mg twice daily; film-coated tablets for oral administration) on the basis of mean 24-h UFC concentration and safety until week 12. In period 2, weeks 13-24, osilodrostat was continued at the therapeutic dose determined during period 1. In period 3, beginning at week 26, participants who had a mean 24-h UFC concentration of less than or equal to the ULN at week 24, without up-titration after week 12, were randomly assigned (1:1), via an interactive-response technology, stratified by osilodrostat dose at week 24 and history of pituitary irradiation, to continue osilodrostat or switch to placebo for 8 weeks. Participants and investigators were masked to treatment assignment. Ineligible participants continued open-label osilodrostat. In period 4, weeks 35-48, all participants were given open-label osilodrostat until core-study end. The primary objective was to compare the efficacy of osilodrostat versus placebo at the end of period 3. The primary endpoint was the proportion of participants who had been randomly assigned to treatment or placebo with a complete response (ie, mean 24-h UFC concentration of ≤ULN) at the end of the randomised withdrawal period (week 34), without up-titration during this period. The key secondary endpoint was the proportion of participants with a complete response at the end of the single-arm, open-label period (ie, period 2, week 24) without up-titration during weeks 13-24. Analysis was by intention-to-treat for all patients who received at least one dose of osilodrostat (full analysis set; key secondary endpoint) or randomised treatment (randomised analysis set; primary endpoint) and safety was assessed in all enrolled patients who received at least one dose of osilodrostat and had at least one post-baseline safety assessment. LINC 3 is registered with ClinicalTrials.gov, NCT02180217, and is now complete. FINDINGS: Between Nov 12, 2014, and March 22, 2017, 202 patients were screened and 137 were enrolled. The median age was 40·0 years (31·0-49·0) and 106 (77%) participants were female. 72 (53%) participants were eligible for randomisation during the withdrawal phase, of whom 36 were assigned to continue osilodrostat and 35 were assigned to placebo; one patient was not randomly assigned due to investigator decision and continued open-label osilodrostat. More patients maintained a complete response with osilodrostat versus with placebo at week 34 (31 [86%] vs ten [29%]; odds ratio 13·7 [95% CI 3·7-53·4]; p<0·0001). At week 24, 72 (53%; 95% CI 43·9-61·1) of 137 patients maintained a complete response without up-titration after week 12. Most common adverse events (ie, occurred in >25% of participants) were nausea (57 [42%]), headache (46 [34%]), fatigue (39 [28%]), and adrenal insufficiency (38 [28%]). Hypocortisolism occurred in 70 (51%) patients and adverse events related to adrenal hormone precursors occurred in 58 (42%) patients. One patient died, unrelated to study drug, after the core study phase. INTERPRETATION: Twice-daily osilodrostat rapidly reduced mean 24-h UFC and sustained this reduction alongside improvements in clinical signs of hypercortisolism; it was also generally well tolerated. Osilodrostat is an effective new treatment option that is approved in Europe for the treatment of endogenous Cushing's syndrome and in the USA for Cushing's disease. FUNDING: Novartis Pharma AG.


Assuntos
Citocromo P-450 CYP11B2/antagonistas & inibidores , Imidazóis/administração & dosagem , Hipersecreção Hipofisária de ACTH/diagnóstico , Hipersecreção Hipofisária de ACTH/tratamento farmacológico , Piridinas/administração & dosagem , Administração Oral , Adulto , Citocromo P-450 CYP11B2/metabolismo , Método Duplo-Cego , Feminino , Humanos , Hidrocortisona/antagonistas & inibidores , Hidrocortisona/metabolismo , Masculino , Pessoa de Meia-Idade , Hipersecreção Hipofisária de ACTH/metabolismo , Estudos Prospectivos , Resultado do Tratamento
9.
PLoS One ; 15(6): e0233979, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32492052

RESUMO

BACKGROUND: Exposure to maternal stress during pregnancy can have adverse effects on the fetus, which has potential long-term effects on offspring´s development and health. We investigated the kinetics and metabolism of the hormones and amino acids: cortisol, cortisone, tryptophan and serotonin in the term placenta in an ex vivo human placental perfusion model. The placentas used in the experiments were donated from families participating in the Maternal Stress and Placental Function project with a known maternal stress background. METHOD: Cortisol, cortisone, tryptophan and serotonin were added simultaneously to the maternal side in the 6 hour ex vivo term human recirculating placental perfusion model, in four experimental set-ups: without inhibitors, with carbenoxolone -that inhibits cortisol metabolism into cortisone, with fluoxetine that inhibits the serotonin transporter, and with PCPA that inhibits metabolism of tryptophan into serotonin. The concentration of cortisol and cortisone, and tryptophan and serotonin were quantified using UPLC and HPLC-MS respectively. RESULTS: Cortisol was rapidly metabolized into cortisone in the placenta, to a somewhat lesser degree when adding the inhibitor carbenoxolone, resulting in higher fetal exposure to cortisol. Serotonin was also rapidly metabolized in the placenta. When adding fluoxetine a peak of fetal serotonin levels was seen in the first hour of the perfusion. No effect was seen of the maternal stress levels on placental transport kinetics in this study. CONCLUSION: Inhibiting the metabolism of cortisol in the placenta increased fetal exposure to cortisol as expected. Unexpectedly we saw an increased fetal exposure to serotonin when inhibiting the serotonin transporter, which may be related to the increased serotonin concentration on the maternal side of the placenta. No effect on placental kinetics were evident on maternal stress levels during the pregnancy as the majority of participating mothers had normal stress levels.


Assuntos
Feto/metabolismo , Troca Materno-Fetal , Placenta/metabolismo , Estresse Psicológico/metabolismo , Adulto , Cortisona/metabolismo , Feminino , Humanos , Hidrocortisona/metabolismo , Perfusão , Gravidez , Serotonina/metabolismo , Triptofano/metabolismo
10.
PLoS One ; 15(6): e0233718, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32497103

RESUMO

BACKGROUND: Person and environment-related childhood adverse events have been demonstrated to increase the risk of impaired mental health in later life differently for boys and girls. Altered hypothalamic pituitary adrenal (HPA)-axis functioning has been suggested as a key mechanism underlying this association. Cortisol and dehydroepiandrosterone (DHEA) are both output hormones of the HPA-axis. DHEA may have a protective function against long-term exposure to increased levels of cortisol, but has been little investigated in relation to childhood adversity. OBJECTIVE: We aimed to test the associations between person-, and environment-related childhood adversity and levels of cortisol, DHEA and cortisol/DHEA ratio in adolescent boys and girls. METHODS: A total of 215 Dutch adolescents participated in the study and filled out the 27-item Adverse Life Events Questionnaire for the assessment of childhood adversity, which was split up in separate scores for person-related and environment-related events. Cortisol and DHEA concentrations and cortisol/DHEA ratio were determined in proximal 3 cm long hair segments. Additionally, saliva samples were collected immediately and 30 minutes after waking up, at noon and at 8 pm. Multiple linear regression analyses were used to test associations between childhood adversity and cortisol and DHEA concentrations, for boys and girls separately, with age, BMI and pubertal development as covariates. RESULTS: Data were available for 74 boys and 116 girls with a mean age of 15.7 years (SD = 2.0). Higher levels of person-related childhood adversity were associated with higher hair DHEA levels in girls and with higher hair cortisol levels in boys. A trend towards a significant association was observed between higher levels of environment-related childhood adversity and higher DHEA levels in boys. Neither person- nor environment related childhood adversity was associated with cortisol/DHEA ratio. A trend was observed for environment-related childhood adversity and lower daily cortisol output in boys. CONCLUSION: We found differential associations between childhood adversity and cortisol and DHEA levels in girls and boys, for respectively person-related and environment-related childhood adversity. Our findings suggest that different types of childhood adversity are not only linked to levels of cortisol, but also to DHEA concentrations, in a sex-specific manner, with possible future implications for mental health.


Assuntos
Experiências Adversas da Infância , Desidroepiandrosterona/análise , Hidrocortisona/análise , Adolescente , Desidroepiandrosterona/metabolismo , Feminino , Cabelo/química , Humanos , Hidrocortisona/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo , Masculino , Sistema Hipófise-Suprarrenal/metabolismo , Saliva/química , Autorrelato , Fatores Sexuais , Estresse Psicológico/metabolismo
11.
Vet J ; 259-260: 105458, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32553232

RESUMO

Two sensitive assays based on AlphaLISA technology were developed and validated for the measurement of cortisol and cortisone in hair of pigs, that also enabled estimation of 11ß-hydroxysteroid dehydrogenase type 2 activity. These assays were applied to hair samples from sows (n = 32) collected at 5 days before, and at 23 and 59 after farrowing, in reproductive cycles in two different periods: spring-summer (n = 16) and winter-spring (n = 16). The assays were precise (imprecision <12%) and accurate (recovery range, 80-115%) for cortisol and cortisone determination. Hair cortisone concentrations and the cortisone/cortisol ratio (an estimate of 11ß-hydroxysteroid dehydrogenase isoenzyme type 2 activity) increased after farrowing more than cortisol, being these changes of higher magnitude during periods of higher atmospheric temperature. The measurement of hair cortisone concentrations and estimations of the activity of the 11ß-hydroxysteroid dehydrogenase isoenzyme type 2, measured by the assays developed in this study, are complementary biomarkers to hair cortisol, and can increase at periods associated with stress, such as farrowing and lactation, especially at high atmospheric temperatures. .


Assuntos
Ciclo Estral/fisiologia , Cabelo/metabolismo , Suínos/fisiologia , 11-beta-Hidroxiesteroide Desidrogenase Tipo 2/metabolismo , Animais , Biomarcadores/metabolismo , Cortisona/metabolismo , Ciclo Estral/metabolismo , Feminino , Hidrocortisona/metabolismo , Reprodução , Estações do Ano , Temperatura
12.
PLoS One ; 15(6): e0234971, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32584863

RESUMO

Intensive pig management involves in a commercial setting the housing and implementation of certain procedures, such as castration and tail docking, which may be stressful for the animal. Good farming practices include the reduction of stress due to management processes, but assessing the level of stress perceived entirely through behavioural observations can be challenging. The monitoring stress-related physiological markers, like glucocorticoids (GC), can be an accurate alternative that would presumably be more objective. In order to avoid an additional stressor by taking blood, a non-invasive approach is advisable. We used an adrenocorticotropic hormone (ACTH) stimulation test and the effect of transport to examine the suitability of different enzyme immunoassays (EIAs) for monitoring adrenocortical function in domestic pigs using saliva and faeces as sample matrices. An assay measuring faecal glucocorticoid metabolites (fGCMs) with a 3ß,11ß-diol group has proven suited to determine adrenocortical activity, showing an overall increase of 180% in fGCM concentrations related to ACTH administration and of 70% related to transport, respectively. A cortisol EIA was used to detect salivary glucocorticoid (sGC) concentrations, revealing a 1100% increase in sGC concentrations after ACTH administration. The stability of fGCM concentrations post-defecation was determined to assess possible changes in measured fGCM concentrations in unpreserved faecal material over time, with fGCM concentrations being relatively stable (maximal 12% change) under natural conditions for approximately two days after defecation. This implicates that untreated faecal material from pigs can be analysed for up to two days after collection without appreciable level of depreciation in fGCM concentrations. Being able to assess the physiological stress response of domestic pigs non-invasively can help to improve the well-being of commercially reared pigs.


Assuntos
Hormônio Adrenocorticotrópico/análise , Bem-Estar do Animal , Hidrocortisona/análise , Estresse Fisiológico , Sus scrofa , Córtex Suprarrenal/metabolismo , Hormônio Adrenocorticotrópico/metabolismo , Criação de Animais Domésticos/métodos , Animais , Ritmo Circadiano/fisiologia , Fezes/química , Feminino , Hidrocortisona/metabolismo , Saliva/química
13.
Crim Behav Ment Health ; 30(2-3): 117-131, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32535969

RESUMO

BACKGROUND: Early puberty is associated with higher than average risk of antisocial behaviour, both in girls and boys. Most studies of such association, however, have focused on psychosocial mediating and moderating factors. Few refer to coterminous hormonal measures. AIM: The aim of this review is to consider the role of hormonal markers as potential mediating or moderating factors between puberty timing and antisocial behaviour. METHOD: A systematic literature search was conducted searching Medline, Embase, Web of Science, Scopus, Psycinfo, Cochrane and Google Scholar. RESULTS: Just eight studies were found to fit criteria, all cross-sectional. Measurements were too heterogeneous to allow meta-analysis. The most consistent associations found were between adrenal hormones-both androgens and cortisol-which were associated with early adrenarche and antisocial behaviours in girls and later adrenarche and antisocial behaviour in boys. CONCLUSIONS: The findings from our review suggest that longitudinal studies to test bidirectional hormone-behaviour associations with early or late puberty would be worthwhile. In view of the interactive processes between hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal axes, integrated consideration of the hormonal end products is recommended.


Assuntos
Comportamento do Adolescente/psicologia , Adrenarca/psicologia , Transtorno da Personalidade Antissocial/etiologia , Hormônios/sangue , Menarca/fisiologia , Puberdade/fisiologia , Maturidade Sexual/fisiologia , Adolescente , Comportamento do Adolescente/fisiologia , Adrenarca/fisiologia , Androgênios , Transtorno da Personalidade Antissocial/diagnóstico , Transtorno da Personalidade Antissocial/metabolismo , Criança , Feminino , Hormônios Esteroides Gonadais/sangue , Gonadotropinas Hipofisárias/sangue , Humanos , Hidrocortisona/metabolismo , Masculino , Fatores de Tempo
14.
Psychopharmacology (Berl) ; 237(8): 2305-2316, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32506233

RESUMO

RATIONAL: The ability of conditioned stimuli to affect instrumental responding is a robust finding from animal as well as human research and is assumed as a key factor regarding the development and maintenance of addictive behaviour. OBJECTIVES: While it is well known that stress is an important factor for relapse after treatment, little is known about the impact of stress on conditioned substance-associated stimuli and their influence on instrumental responding. METHODS: We administered in the present study a Pavlovian-to-instrumental transfer (PIT) paradigm with stimuli associated with smoking- and chocolate-related rewards using points in a token economy to light to moderate smokers who also indicated to like eating chocolate. After completion of the first two phases of the PIT paradigm (i.e. Pavlovian training and instrumental trainings), participants were randomly allocated to the socially evaluated cold pressor test or a control condition before the final phase of the PIT paradigm, the transfer phase, was administered. RESULTS: The presentation of a smoking-related stimulus enhanced instrumental responding for a smoking-related reward (i.e. 'smoking-PIT' effect) and presentation of a chocolate-related stimulus for a chocolate-related reward (i.e. 'chocolate-PIT' effect) in participants aware of the experimental contingencies as indicated by expectancy ratings. However, acute stress did not change (i.e. neither enhanced nor attenuated) the 'smoking-PIT' effect or the 'chocolate-PIT' effect, and no overall effect of acute stress on tobacco choice was observed in aware participants. CONCLUSIONS: The established role of stress in addiction appears not to be driven by an augmenting effect on the ability of drug stimuli to promote drug-seeking.


Assuntos
Condicionamento Clássico/fisiologia , Recompensa , Estresse Psicológico/psicologia , Transtornos Relacionados ao Uso de Substâncias/psicologia , Transferência de Experiência/fisiologia , Doença Aguda , Adolescente , Adulto , Animais , Comportamento Aditivo/metabolismo , Comportamento Aditivo/psicologia , Temperatura Baixa/efeitos adversos , Feminino , Humanos , Hidrocortisona/análise , Hidrocortisona/metabolismo , Masculino , Distribuição Aleatória , Estresse Psicológico/metabolismo , Transtornos Relacionados ao Uso de Substâncias/metabolismo , Adulto Jovem
15.
PLoS One ; 15(5): e0230704, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32357152

RESUMO

BACKGROUND: Cortisol has been used to capture psychophysiological stress during childbirth and postpartum wellbeing. We explored the effect of a brief antenatal training course in self-hypnosis on salivary cortisol during childbirth and 6 weeks postpartum. METHODS: In a randomized, controlled trial conducted at Aarhus University Hospital Skejby Denmark during the period January 2010 until October 2010, a total of 349 healthy nulliparous women were included. They were randomly allocated to a hypnosis group (n = 136) receiving three one-hour lessons in self-hypnosis with additional audio-recordings, a relaxation group (n = 134) receiving three one-hour lessons in various relaxation methods with audio-recordings for additional training, and a usual care group (n = 79) receiving ordinary antenatal care only. Salivary cortisol samples were collected during childbirth (at the beginning of the pushing state, 30 minutes, and 2 hours after childbirth), and 6 weeks postpartum (at wake up, 30 minutes after wake up, and evening). Cortisol concentrations were compared using a linear mixed-effects model. Correlations between cortisol concentrations and length of birth, experienced pain and calmness during birth were examined by a Spearman rank correlation test. FINDINGS: During childbirth, week correlations were found between cortisol concentrations 30 minutes after childbirth and length of birth. In the beginning of the pushing state and 2 hours after childbirth, we found a tendency towards higher cortisol concentrations in the hypnosis group compared to the other two groups (hypnosis versus relaxation p = 0.02 and 0.03, hypnosis versus usual care p = 0.08 and 0.05). No differences were observed in cortisol concentrations between the groups 30 minutes after childbirth (hypnosis versus relaxation p = 0.08, hypnosis versus usual care 0.10) or 6 weeks postpartum (hypnosis versus relaxation: p = 0.85, 0.51, and 0.68, hypnosis versus usual care: p = 0.85, 0.93, and 0.96). CONCLUSION: Antenatal hypnosis training may increase the release of cortisol during childbirth with no long-term consequences. Further research is needed to help interpret these findings.


Assuntos
Hipnose/métodos , Dor do Parto/terapia , Parto/metabolismo , Terapia de Relaxamento , Adulto , Analgesia Obstétrica/efeitos adversos , Parto Obstétrico , Feminino , Humanos , Hidrocortisona/metabolismo , Dor do Parto/metabolismo , Dor do Parto/fisiopatologia , Trabalho de Parto/fisiologia , Parto/fisiologia , Satisfação do Paciente , Período Pós-Parto/metabolismo , Período Pós-Parto/fisiologia , Gravidez , Cuidado Pré-Natal , Saliva/metabolismo
16.
Adv Exp Med Biol ; 1195: 59-71, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32468460

RESUMO

Herein, we deploy an in silico pipeline of structural bioinformatics, thermodynamics, and molecular dynamics to investigate the role of cortisol in circadian rhythms, biorhythms, stress response, and even sleep disorders. Our study shows that high concentrations of cortisol intercalate in the minor groove of DNA. This phenomenon widens the adjacent major grooves and provides the Clock/Bmal1 complex with more space to dock and interact with DNA. Then, the strong charges of cortisol pull the alpha helices of the Clock/Bmal1 complex and bend it inward, thus establishing stronger interactions and prolonged signaling. Our results indicate that elevated cortisol levels play an important role in stress, inflammation, and sleep disorders as a result of prolonged and stronger dsDNA - Clock/Bmal1 interactions.


Assuntos
Fatores de Transcrição ARNTL/metabolismo , Proteínas CLOCK/metabolismo , DNA/química , Hidrocortisona/metabolismo , Sistema Hipotálamo-Hipofisário/fisiologia , Sistema Hipófise-Suprarrenal/fisiologia , Transtornos do Sono-Vigília/fisiopatologia , Estresse Psicológico/prevenção & controle , Ritmo Circadiano/genética , Ritmo Circadiano/fisiologia , Simulação por Computador , DNA/metabolismo , Humanos , Hidrocortisona/química , Inflamação/genética , Inflamação/metabolismo , Substâncias Intercalantes/química , Substâncias Intercalantes/metabolismo , Receptores de Glucocorticoides/metabolismo , Transtornos do Sono-Vigília/genética , Estresse Psicológico/genética , Estresse Psicológico/fisiopatologia
17.
Int J Behav Med ; 27(3): 262-266, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32405916

RESUMO

BACKGROUND: Accurate estimation in statistical models depends on sample size but also, critically, reliability of the measure. Physiometrics is the equivalent of psychometrics for measures such as sex hormones, catabolic hormones, and products of the immune system. METHOD: There are multiple ways to measure physiometrics, from simple correlation to complex generalizability theory designs. Depending on the design, these estimates can provide information about equivalency (e.g., the correlation between two measurements taken close together in time) or stability (e.g., the correlation between two measurements taken farther apart in time). RESULTS: The physiometrics of salivary measures including cortisol, α-amylase, testosterone, and cytokines range from highly stable, requiring only a single sample, to highly unstable, requiring multiple samples to achieve generalizability to longer periods of time. However, generalizability is relative to the study design, and only some designs call for stable and generalizable measures. CONCLUSION: Both dedicated physiometric studies and more reporting of physiometrics in psychoneuroendocrinology and psychoneuroimmunology will improve the quality of salivary bioscience study designs in the future.


Assuntos
Hidrocortisona/metabolismo , Saliva/metabolismo , Humanos , Reprodutibilidade dos Testes , Projetos de Pesquisa , Testosterona/metabolismo
18.
Int J Sports Physiol Perform ; 15(6): 808-815, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32365286

RESUMO

The growing prevalence and popularity of interval training necessitate additional guidelines in regard to maximal levels of time and intensity. PURPOSE: To correlate salivary hormones and time in varying heart-rate (HR) zones. The hypothesis was that chronic exercise durations >9% of total exercise time in the >90% maximum HR zone would lead to decreased variation in salivary cortisol concentration after exercise in a 2-bout high-intensity protocol compared with less or more time in this zone. METHODS: A total of 35 healthy adults who regularly exercised for an average of 8 hours per week recorded their HR during every training session for 3 weeks. Later, they completed an experimental day composed of two 30-minute high-intensity interval sessions separated by 4 hours of nonactive recovery. The authors collected saliva samples before, immediately following, and 30 minutes after each exercise session to assess changes in cortisol concentrations. RESULTS: There was a correlation between weekly time training at an intensity >90% maximum HR and the variables associated with overtraining. Salivary cortisol concentration fluctuated less in the participants who exercised in this extreme zone for >40 minutes per week (P < .001). CONCLUSION: Based on the current study data, for individuals who regularly exercise, 4% to 9% total training time above 90% maximum HR is the ideal duration to maximize fitness and minimize symptoms related to overreaching.


Assuntos
Exercício Físico/fisiologia , Frequência Cardíaca/fisiologia , Treinamento Intervalado de Alta Intensidade/métodos , Hidrocortisona/metabolismo , Saliva/metabolismo , Adulto , Afeto/fisiologia , Aptidão Cardiorrespiratória/fisiologia , Aptidão Cardiorrespiratória/psicologia , Metabolismo Energético , Exercício Físico/psicologia , Feminino , Treinamento Intervalado de Alta Intensidade/psicologia , Humanos , Masculino , Sono/fisiologia , Fatores de Tempo
19.
Internist (Berl) ; 61(6): 565-572, 2020 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-32394073

RESUMO

BACKGROUND: The central circadian pacemaker in the suprachiasmatic nucleus and interaction of clock genes with the hypothalamus pituitary adrenal axis are responsible for very distinct cortisol concentrations. Unphysiologically high doses of glucocorticoids that do not follow the circadian rhythm lead to increased rates of morbidity, mortality and reduced quality of life. OBJECTIVES: Does a switch to modified-release hydrocortisone in multimorbid elderly patients offer benefits compared to a conventional therapy regime? METHODS: Evaluation, analysis and discussion of statistics, recent research results and expert advice. RESULTS: Overdosage and unphysiological timing of cortisol administration result in higher incidences of obesity, hypertension, hyperglycemia, coronary heart disease and cardiac events. Body weight, body mass index and HbA1c decline with Plenadren® (Shire Pharmaceuticals Ireland Limited, Dublin, Ireland) treatment compared to conventional therapy. CD16+ natural killer cells and natural killer cytotoxycity are reduced, and the incidence of respiratory-tract infections is increased, with conventional therapy compared to Plenadren®. Cortisol influences sleep pattern and sleep quality by its circadian secretion. CONCLUSION: Novel modified-release hydrocortisone preparations offer diverse benefits with regard to their effect on metabolism, cardiovascular risk, immunity and sleep, which might be beneficial in particular in multimorbid elderly.


Assuntos
Insuficiência Adrenal/tratamento farmacológico , Ritmo Circadiano/fisiologia , Glucocorticoides/uso terapêutico , Terapia de Reposição Hormonal/métodos , Hidrocortisona/uso terapêutico , Insuficiência Adrenal/metabolismo , Idoso , Relação Dose-Resposta a Droga , Esquema de Medicação , Cálculos da Dosagem de Medicamento , Glucocorticoides/administração & dosagem , Humanos , Hidrocortisona/administração & dosagem , Hidrocortisona/metabolismo , Qualidade de Vida , Resultado do Tratamento
20.
Clin Ter ; 171(3): e197-e208, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32323706

RESUMO

PURPOSE: Stress is a multifactorial and complex pathway, gaining growing attention from the healthcare community. Surgeons are subjected to higher levels of stress, due to surgical procedures that are demanding and repetitive; unfortunately, high-stress levels may also cause side-effects, as surgical mistakes. This study aimed to evaluate the efficacy of specific probiotics strains formula on stress levels in oral and maxillofacial surgeons, to improve their quality of life. METHODS: We have investigated the hormonal (salivary Cortisol; sC), immune (salivary Immunoglobulin A; sIgA) and cardiovascular (Heart rate, HR, and systolic blood pressure, SBP) responses induced by stress conditions in 40 oral surgeons, randomly selected and allocated, according to their experience level, in three categories: senior, expert, and junior. RESULTS: The results described how the number of heartbeats/ minute and SBP are slightly raised in all surgeons at different timepoints. Such data allow us to assess that work-related stress can induce an increase in cardiovascular parameters, even if they are not significantly modified by the use of probiotics. On the other hand, our data indicate that 10 weeks of probiotic integration may induce the improvement of other stress-related physiological parameters in oral surgeons with different degrees of surgical experience, such as the salivary cortisol levels, even under stress conditions. Moreover, in the test group (probiotics administration), the immunoglobulin levels were higher than the control (placebo administration) group: this happens as a consequence of the regular use of probiotics, which may induce an increased number of IgA producing cells. DISCUSSION: Our data indicated that 10 weeks of probiotics-enriched diet modify some stress-related physiological parameters in oral surgeons with different degrees of surgical experience, but it does not impact on the overall cardiovascular risk.


Assuntos
Cirurgiões Bucomaxilofaciais/psicologia , Probióticos/uso terapêutico , Estresse Fisiológico/efeitos dos fármacos , Adulto , Pressão Sanguínea , Competência Clínica , Método Duplo-Cego , Frequência Cardíaca , Humanos , Hidrocortisona/metabolismo , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Saliva/metabolismo
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