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2.
Int J Nanomedicine ; 16: 2203-2217, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33762821

RESUMO

Background: It is well known that smoking is harmful to health; however, it can also ameliorate anxiety. To date, it is unclear whether any nanoparticles found in cigarette mainstream smoke (CS) contribute to this effect. Aim: The aim of this study was to assess the particle composition of CS to identify novel anti-anxiety components. Methods: Carbon dots (CDs) from CS (CS-CDs) were characterised using high-resolution transmission electron microscopy, Fourier-transform infrared, ultraviolet, fluorescence, X-ray photoelectron spectroscopy, X-ray diffraction and high-performance liquid chromatography. The anti-anxiety effects of CS-CDs in mouse models were evaluated and confirmed with the elevated plus maze and open-field tests. Results: The quantum yield of CS-CDs was 13.74%, with a composition of C, O, and N. In addition, the surface groups contained O-H, C-H, C=O, C-N, N-H, C-O-C, and COO- bonds. Acute toxicity testing revealed that CS-CDs had low in vitro and in vivo toxicity within a certain concentration range. The results of the elevated plus maze and open-field tests showed that CS-CDs had a significant anti-anxiety effect and a certain sedative effect in mice. The mechanism of these effects may be related to the decrease in glutamate levels and promotion of norepinephrine production in the mouse brain, and the decrease in dopamine in mouse serum due to CS-CDs. Conclusion: CS-CDs may have anti-anxiety and certain sedative effects. This study provides a new perspective for a more comprehensive understanding of the components, properties, and functions of CS. Furthermore, it offers a novel target for the development of smoking cessation treatments, such as nicotine replacement therapy.


Assuntos
Comportamento Animal , Carbono/química , Fumar Cigarros/efeitos adversos , Sistema Endócrino/metabolismo , Neurotransmissores/metabolismo , Pontos Quânticos/química , Água/química , Hormônio Adrenocorticotrópico/sangue , Animais , Ansiedade/sangue , Ansiedade/patologia , Encéfalo/metabolismo , Encéfalo/patologia , Cromatografia Líquida de Alta Pressão , Corticosterona/sangue , Hormônio Liberador da Corticotropina/sangue , Dopamina/sangue , Masculino , Camundongos , Camundongos Endogâmicos ICR , Espectroscopia Fotoeletrônica , Pontos Quânticos/ultraestrutura , Células RAW 264.7 , Espectrometria de Fluorescência , Espectroscopia de Infravermelho com Transformada de Fourier , Análise Espectral Raman , Testes de Toxicidade Aguda , Difração de Raios X
4.
Biomed Pharmacother ; 133: 111060, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33378969

RESUMO

The present study aims to reveal the compositions of Zhenshu TiaoZhi formula (FTZ) comprehensively, and investigate whether FTZ ameliorate glucolipid metabolism disorders in diabetic rats with the involvement of glucocorticoids in peripheral insulin-sensitive tissues. The fingerprint was established based on 11 batches of FTZ samples and chemical compostions of FTZ were identified by ultra performance liquid chromatography-time of flight/mass spectrometry (UPLC-TOF/MS). High-fat diet (HFD) and streptozotocin (STZ) induced diabetic rats were orally administrated with 3 and 6 g/kg body weight of FTZ for 8 weeks. Indices of glucolipid metabolism, including fasting blood glucose (FBG), fasting insulin, insulin resistance index (IRI) and blood lipids were evaluated after treatment of FTZ. The levels of HPA axis hormones were examined. Reverse transcription-polymerase chain reaction (RT-PCR) was adopted to investigate the relative mRNA expressions of 11ß-hydroxysteroid dehydrogenase 1 (11ß-HSD1) and glucolipid metabolic indicators. A reference fingerprint was established and 93 compounds of FTZ were tentatively identified. In vivo, FTZ treatment exerted antidiabetic and antidyslipidemic effects while decreased the level of corticotropin releasing hormone (CRH). 11ß-HSD1 mRNA showed similar trajectory in both liver, adipose and skeletal muscle tissues, which was up-regulated in diabetic group and ameliorated in FTZ groups. Furthermore, the expressions of glucose-6-phosphatase (G6Pase), phosphoenolpyruvate carboxykinase (PEPCK) and adipose triglyceride lipase (ATGL) were down-regulated in liver and skeletal muscle. These results elucidated the compositions of FTZ comprehensively and indicated its effect on ameliorating glucolipid metabolism of diabetic rats involved hypothalamus-pituitary-adrenal (HPA) axis homeostasis. Down-regulating 11ß-HSD1 in insulin-sensitive tissues might be a potential mechanism of FTZ in treating type 2 diabetes mellitus (T2DM).


Assuntos
Glicemia/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Hipoglicemiantes/análise , Hipoglicemiantes/farmacologia , Hipolipemiantes/farmacologia , Lipídeos/sangue , 11-beta-Hidroxiesteroide Desidrogenase Tipo 1/genética , 11-beta-Hidroxiesteroide Desidrogenase Tipo 1/metabolismo , Hormônio Adrenocorticotrópico/sangue , Animais , Biomarcadores/sangue , Glicemia/metabolismo , Cromatografia Líquida de Alta Pressão , Corticosterona/sangue , Hormônio Liberador da Corticotropina/sangue , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/induzido quimicamente , Hipolipemiantes/isolamento & purificação , Resistência à Insulina , Masculino , Espectrometria de Massas , Ratos Sprague-Dawley , Estreptozocina
5.
Biochem Biophys Res Commun ; 535: 1-5, 2021 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-33340760

RESUMO

Reactive oxygen species (ROS) are highly reactive and directly attack surrounding biomolecules to deteriorate cellular and tissue functions. Meanwhile, ROS also serve as signaling mediators to upregulate pro-inflammatory cytokine expression via activation of the nuclear factor kappa B signaling pathway, and the increased pro-inflammatory cytokines trigger respiratory burst of inflammatory cells that further accelerates ROS production in the inflamed tissue. Such crosstalk between ROS and inflammatory responses leads to a chain reaction of negativity, and cause progression of several chronic pathologies. Since molecular hydrogen is known to preferentially remove cytotoxic hydroxyl radicals and peroxynitrites, and to prevent cell and tissue damage, we here examined whether electrolyzed hydrogen water (EHW) enriched with molecular hydrogen and reactive hydrogen storing platinum nanoparticles dissolved from an electrode could alleviate oxidative stress and inflammation induced by continuous stress challenges. Five-day continuous stress loading to rats elevated reactive oxygen metabolites-derived compounds (d-ROMs), interleukin (IL)-1ß, and adrenocorticotropic hormone (ACTH) levels and decreased the biological antioxidant potential (BAP) level. Drinking EHW during 5-day continuous stress loading significantly alleviated all of these changes. The results suggest that EHW could suppress stress-response-associated oxidative stress and IL-1ß level elevation in vivo, and that drinking of EHW is effective for controlling stress responses via its antioxidant potential.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Eletrólise , Hidrogênio/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Água/farmacologia , Hormônio Adrenocorticotrópico/sangue , Animais , Eletrodos , Hidrogênio/administração & dosagem , Inflamação/sangue , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Interleucina-18/sangue , Masculino , Ratos , Espécies Reativas de Oxigênio/metabolismo , Água/administração & dosagem
6.
Phytomedicine ; 81: 153436, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33360346

RESUMO

BACKGROUND: Depression is a pervasive or persistent mental disorder that causes mood, cognitive and memory deficits. Uncaria rhynchophylla has been widely used to treat central nervous system diseases for a long history, although its efficacy and potential mechanism are still uncertain. PURPOSE: The present study aimed to investigate anti-depression effect and potential mechanism of U. rhynchophylla extract (URE). STUDY DESIGN AND METHODS: A mouse depression model was established using unpredictable chronic mild stress (UCMS). Effects of URE on depression-like behaviours, neurotransmitters, and neuroendocrine hormones were investigated in UCMS-induced mice. The potential target of URE was analyzed by transcriptomics and bioinformatics methods and validated by RT-PCR and Western blot. The agonistic effect on 5-HT1A receptor was assayed by dual-luciferase reporter system. RESULTS: URE ameliorated depression-like behaviours, and modulated levels of neurotransmitters and neuroendocrine hormones, including 5-hydroxytryptamine (5-HT), 5-hydroxyindole acetic acid (5-HIAA), dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), corticosterone (CORT), corticotropin-releasing hormone (CRH), and adrenocorticotropic hormone (ACTH), in UCMS-induced mice. Transcriptomics and bioinformatics results indicated that URE could regulate glutamatergic, cholinergic, serotonergic, and GABAergic systems, especially neuroactive ligand-receptor and cAMP signaling pathways, revealing that Htr1a encoding 5-HT1A receptor was a potential target of URE. The expression levels of downstream proteins of 5-HT1A signaling pathway 5-HT1A, CREB, BDNF, and PKA were increased in UCMS-induced mice after URE administration, and URE also displayed an agonistic effect against 5-HT1A receptor with an EC50 value of 17.42 µg/ml. CONCLUSION: U. rhynchophylla ameliorated depression-like behaviours in UCMS-induced mice through activating 5-HT1A receptor.


Assuntos
Antidepressivos/farmacologia , Depressão/tratamento farmacológico , Agonistas do Receptor 5-HT1 de Serotonina/farmacologia , Uncaria/química , Hormônio Adrenocorticotrópico/sangue , Animais , Antidepressivos/química , Biologia Computacional , Corticosterona/sangue , Hormônio Liberador da Corticotropina/sangue , Depressão/genética , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Extratos Vegetais/farmacologia , Receptor 5-HT1A de Serotonina , Serotonina/metabolismo , Estresse Psicológico
7.
Vet J ; 266: 105562, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33323174

RESUMO

Pergolide, a dopamine agonist, is commonly administered to manage pituitary pars intermedia dysfunction (PPID), a progressive neurodegenerative disease prevalent in aged horses. However, available evidence regarding pergolide's efficacy in improving clinical and endocrine parameters is limited. The aim of this systematic review was to assess published literature and evaluate evidence regarding whether pergolide treatment results in improvement of clinical signs and/or adrenocorticotrophic hormone (ACTH) concentration compared to no treatment or other unlicensed treatments. Systematic searches of electronic databases were undertaken in April 2019, repeated in August and October 2019, and updated in July 2020. English language publications published prior to these dates were included. Screening, data extraction and quality assessment of publications was undertaken individually by the authors using predefined criteria and subsequently cross-checked. Modified critically appraised topic data collection forms were used to extract data. Due to marked between-study variations, meta-analysis was not undertaken. After removal of duplicate records; 612 publications were identified, of which 129 abstracts were screened for eligibility and 28 publications met criteria for inclusion in the review. Most studies were descriptive case series, cohort studies or non-randomised, uncontrolled field trials. Despite marked variation in study populations, case selection, diagnostic protocols, pergolide dose, follow-up period and outcome measures, in the vast majority of the included studies, pergolide was reported to provide overall clinical improvement in >75% of cases. However, reported improvements in individual clinical signs varied widely. A reduction in plasma ACTH concentrations was reported in 44-74% of cases, while normalisation to within reported reference intervals occurred in 28-74% of cases.


Assuntos
Doenças dos Cavalos/tratamento farmacológico , Pergolida/uso terapêutico , Doenças da Hipófise/veterinária , Adeno-Hipófise Parte Intermédia/efeitos dos fármacos , Hormônio Adrenocorticotrópico/sangue , Animais , Cavalos , Pergolida/administração & dosagem , Doenças da Hipófise/tratamento farmacológico , Resultado do Tratamento
8.
PLoS One ; 15(8): e0235806, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32756565

RESUMO

INTRODUCTION: Oxytocin is a key hormone in breastfeeding. No recent review on plasma levels of oxytocin in response to breastfeeding is available. MATERIALS AND METHODS: Systematic literature searches on breastfeeding induced oxytocin levels were conducted 2017 and 2019 in PubMed, Scopus, CINAHL, and PsycINFO. Data on oxytocin linked effects and effects of medical interventions were included if available. RESULTS: We found 29 articles that met the inclusion criteria. All studies had an exploratory design and included 601 women. Data were extracted from the articles and summarised in tables. Breastfeeding induced an immediate and short lasting (20 minutes) release of oxytocin. The release was pulsatile early postpartum (5 pulses/10 minutes) and coalesced into a more protracted rise as lactation proceeded. Oxytocin levels were higher in multiparous versus primiparous women. The number of oxytocin pulses during early breastfeeding was associated with greater milk yield and longer duration of lactation and was reduced by stress. Breastfeeding-induced oxytocin release was associated with elevated prolactin levels; lowered ACTH and cortisol (stress hormones) and somatostatin (a gastrointestinal hormone) levels; enhanced sociability; and reduced anxiety, suggesting that oxytocin induces physiological and psychological adaptations in the mother. Mechanical breast pumping, but not bottle-feeding was associated with oxytocin and prolactin release and decreased stress levels. Emergency caesarean section reduced oxytocin and prolactin release in response to breastfeeding and also maternal mental adaptations. Epidural analgesia reduced prolactin and mental adaptation, whereas infusions of synthetic oxytocin increased prolactin and mental adaptation. Oxytocin infusion also restored negative effects induced by caesarean section and epidural analgesia. CONCLUSIONS: Oxytocin is released in response to breastfeeding to cause milk ejection, and to induce physiological changes to promote milk production and psychological adaptations to facilitate motherhood. Stress and medical interventions during birth may influence these effects and thereby adversely affect the initiation of breastfeeding.


Assuntos
Aleitamento Materno , Lactação/sangue , Ocitocina/sangue , Hormônio Adrenocorticotrópico/sangue , Ansiedade/sangue , Feminino , Humanos , Hidrocortisona/sangue , Lactação/fisiologia , Gravidez , Prolactina/sangue , Estresse Fisiológico
9.
Eur J Endocrinol ; 183(3): 325-333, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32717717

RESUMO

Objective: To identify radiologic features that correlate with mild autonomous cortisol excess using planar and volumetric analysis. Design: Cross-sectional study. Methods: In the study, 64 patients with overt Cushing syndrome (CS), 59 patients with mild autonomous cortisol excess (MACE), and 64 patients with nonfunctioning adrenal tumors (NFAT) with evaluable CT scans were included. Patients with NFAT and MACE were BMI-matched with those with overt CS. Planar and volumetric analyses of CT scans were performed in DICOM images using OsiriX software. Results: The mean age was 56.6 ± 1.01 years, and 123 patients (65.1%) were female. In the order of NFAT, MACE, and overt CS, the diameters and volumes of the adenoma increased, while limb widths and volumes of the contralateral adrenal gland decreased. Patients with MACE or overt CS were more likely to have osteoporosis than those with NFAT (P = 0.006), and patients with overt CS were more likely to experience a fragility fracture than those with NFAT or MACE (P = 0.002). Among radiologic features, the limb width of the contralateral adrenal gland correlated with the cortisol level after overnight dexamethasone suppression test (r = -0.583, P < 0.001). Conclusions: The study showed that the contralateral adrenal limb thinning was a distinctive radiologic feature of autonomous cortisol excess in the planar and volumetric analysis.


Assuntos
Neoplasias das Glândulas Suprarrenais/sangue , Neoplasias das Glândulas Suprarrenais/patologia , Síndrome de Cushing/sangue , Síndrome de Cushing/patologia , Glândulas Suprarrenais/patologia , Hormônio Adrenocorticotrópico/sangue , Idoso , Índice de Massa Corporal , Estudos Transversais , Feminino , Humanos , Hidrocortisona/sangue , Masculino , Pessoa de Meia-Idade
10.
Toxicol Lett ; 331: 33-41, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32445661

RESUMO

This study was intended to demonstrate that prenatal dexamethasone exposure (PDE) can induce low basal activity of the hypothalamic-pituitary-adrenal axis (HPAA) in male offspring rats and explore the underlying mechanism. Pregnant rats were subcutaneously administered 0.2 mg/kg/d dexamethasone from gestational day (GD) 9 to GD20. Male GD20 fetuses and postnatal day 85 adult male offspring rats were sacrificed under anesthesia. Hypothalamic cells were from GD20∼postnatal day (PD) 7 fetal male rats, treated with different concentrations of dexamethasone and the glucocorticoid receptor (GR) antagonist mifepristone for 5 days. The results suggested that dexamethasone enhanced the expression of hypothalamic L-glutamic acid decarboxylase (GAD) 67 by activating GR, further stimulating the conversion of glutamate to gamma-aminobutyric acid (GABA) and inducing an imbalance in glutamatergic/GABAergic afferents in the hypothalamic paraventricular nucleus (PVN). This imbalance change was maintained postnatally, leading to the inhibition of parvocellular neurons, and mediating the low basal activity of the HPAA in PDE offspring rats, which was manifested by decreased levels of blood adrenocorticotropic hormone and corticosterone as well as reduced expression levels of corticotrophin-releasing hormone (CRH) and arginine vasopressin (AVP) in the hypothalamus. Programming of a developmental imbalance in glutamatergic/GABAergic afferents in the PVN is a potential mechanism responsible for low basal activity of the HPAA in male PDE rats.


Assuntos
Dexametasona/toxicidade , Ácido Glutâmico/metabolismo , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Neurônios Aferentes/efeitos dos fármacos , Núcleo Hipotalâmico Paraventricular/efeitos dos fármacos , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Ácido gama-Aminobutírico/metabolismo , Hormônio Adrenocorticotrópico/sangue , Animais , Animais Recém-Nascidos , Arginina Vasopressina/metabolismo , Corticosterona/sangue , Feminino , Desenvolvimento Fetal/efeitos dos fármacos , Retardo do Crescimento Fetal/induzido quimicamente , Retardo do Crescimento Fetal/metabolismo , Glutamato Descarboxilase/metabolismo , Sistema Hipotálamo-Hipofisário/embriologia , Sistema Hipotálamo-Hipofisário/metabolismo , Masculino , Neurônios Aferentes/metabolismo , Núcleo Hipotalâmico Paraventricular/embriologia , Núcleo Hipotalâmico Paraventricular/metabolismo , Sistema Hipófise-Suprarrenal/embriologia , Sistema Hipófise-Suprarrenal/metabolismo , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Ratos
11.
12.
Intern Med ; 59(14): 1731-1734, 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32238722

RESUMO

A 50-year-old man was referred to our department for overt Cushing's syndrome (CS). His plasma cortisol concentrations were 314 µg/L, and his urinary cortisol concentrations were 431 µg/day. The plasma adrenocorticotropic hormone (ACTH) concentration was below the detectable limit. Computed tomography revealed atrophy of both adrenal glands and the presence of a left pararenal tumor. 131I-6ß-iodomethyl-norcholesterol scintigraphy showed an intense uptake by the left pararenal tumor. These findings suggested that the left pararenal tumor was ectopic cortisol-producing adrenocortical adenoma. This case serves as a reminder that 131I-6ß-iodomethyl-norcholesterol scintigraphy is an effective method for diagnosing ACTH-independent CS in which no adrenal tumor has been found.


Assuntos
Neoplasias do Córtex Suprarrenal/sangue , Neoplasias do Córtex Suprarrenal/diagnóstico , Adenoma Adrenocortical/sangue , Adenoma Adrenocortical/diagnóstico , Hormônio Adrenocorticotrópico/sangue , Síndrome de Cushing/sangue , Hidrocortisona/sangue , Humanos , Radioisótopos do Iodo , Masculino , Pessoa de Meia-Idade , Cintilografia/métodos
13.
Metabolism ; 107: 154219, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32240726

RESUMO

BACKGROUND: An adequate metabolic and hormonal response to the switch from rest to exercise is critical for the health benefits of exercise interventions. Previous work suggests that this response is impaired with overweight/obesity but the specific differences between overweight/obese and lean individuals remain unclear. METHODS: We compared glucose and non-esterified fatty acid (NEFA) regulation and the changes of key homeostatic hormones during 45 min of moderate exercise between 17 overweight/obese and 28 lean premenopausal women. For this comparison, we implemented an exercise protocol at 60% of individual peak oxygen uptake, with frequent blood sampling and under fasting conditions. RESULTS: We found that at the same exercise intensity in the overweight/obese and the lean group of women, the metabolic and hormonal response differed. In contrast to the lean group, the overweight/obese group portrayed an activation in the stress axis (adrenocorticotropic hormone (ACTH)/cortisol) and a lower growth hormone (hGH) response and exercise-increase of plasma NEFA. Both groups, however, displayed increased insulin sensitivity during exercise that was accompanied by a normalization of the elevated fasting glucose in the overweight/obese group after 15-20 min. CONCLUSION: We conclude that the response to exercise in overweight/obese subjects indeed differs from that in lean individuals. Additionally, we demonstrate that exercise can elicit beneficial (improved glucose regulation) and unwanted effects (stress axis activation) in overweight/obese subjects at the same time. This second finding suggests that exercise interventions for overweight/obese subjects need careful consideration of intensity and dose in order to achieve the intended results and avoid acute, undesired reactions.


Assuntos
Terapia por Exercício , Exercício Físico , Hormônios/sangue , Obesidade/metabolismo , Obesidade/terapia , Sobrepeso/metabolismo , Sobrepeso/terapia , Hormônio Adrenocorticotrópico/sangue , Adulto , Glicemia/análise , Índice de Massa Corporal , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/terapia , Teste de Esforço , Ácidos Graxos não Esterificados/sangue , Feminino , Hormônio do Crescimento Humano/sangue , Humanos , Insulina/metabolismo , Pré-Menopausa
15.
BMC Endocr Disord ; 20(1): 24, 2020 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-32075632

RESUMO

BACKGROUND: Adrenal insufficiency (AI) in hospitalized patients is a fatal condition if left undiagnosed. Most patients may require an adrenocorticotropic hormone (ACTH) stimulation test to facilitate AI diagnosis. We aim to identify simple biochemical and clinical factors and derive a predictive model to help identify hospitalized patients with biochemical AI who have indeterminate 0800 h serum cortisol levels. METHODS: A seven-year retrospective study was performed in a tertiary care medical center. We identified 128 inpatients who had undergone low-dose or high-dose ACTH stimulation tests. The association between biochemical AI and other factors was evaluated using a logistic regression model clustering by ACTH dose. Stepwise regression analysis was used to demonstrate the predictive model. Diagnostic performance was evaluated using ROC analysis. RESULTS: Of the 128 patients, 28.1% had biochemical AI. The factors associated with biochemical AI were serum random cortisol < 10 µg/dL (OR = 8.69, p < 0.001), cholesterol < 150 mg/dL (OR = 2.64, p = 0.003), sodium < 140 mmol/L (OR = 1.73, p = 0.004)). Among clinical factors, cirrhosis (OR = 9.05, p < 0.001), Cushingoid appearance in those with exogenous steroid use (OR = 8.56, p < 0.001), and chronic kidney disease (OR = 2.21, p < 0.001) were significantly linked to biochemical AI. The AUC-ROC of the final model incorporating all factors was 83%. CONCLUSIONS: These easy-to-perform biochemical tests and easy-to-assess clinical factors could help predict biochemical AI in hospitalized patients with high accuracy. The physician should therefore have a high index of suspicion to perform dynamic tests for AI diagnosis in those who meet the proposed model criteria.


Assuntos
Insuficiência Adrenal/sangue , Insuficiência Adrenal/diagnóstico , Hormônio Adrenocorticotrópico/sangue , Biomarcadores/sangue , Hospitalização/estatística & dados numéricos , Hidrocortisona/sangue , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Estudos Retrospectivos
16.
AJR Am J Roentgenol ; 214(4): 800-807, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32069079

RESUMO

OBJECTIVE. Adrenal incidentalomas occur in 5% of adults and can produce autonomous cortisol secretion that increases the risk of metabolic syndrome and cardiovascular disease. The objective of our study was to evaluate the relationship between adrenal nodule size measured on CT and autonomous cortisol secretion. SUBJECTS AND METHODS. In a prospective study of 73 patients 22-87 years old with incidentalomas, unilateral in 52 patients and bilateral in 21 patients, we measured maximum nodule diameter on CT and serum cortisol levels at 8:00 am, 60 minutes after the adrenocorticotropic hormone stimulation test, and after the dexamethasone suppression test. We also studied 34 age-, sex-, and body mass index-matched control subjects. Statistics used were Spearman correlation coefficients, t tests, ANOVA test, and multivariate analysis. RESULTS. The mean maximum diameter of unilateral nodules measured on CT was larger on the right (2.47 ± 0.98 [SD] cm) than on the left (2.04 ± 0.86 cm) (p = 0.01). In the bilateral cases, the mean diameter of the right nodules was 2.69 ± 0.93 cm compared with 2.13 ± 0.89 cm on the left (p = 0.06). Mean baseline serum cortisol level was significantly higher in the patients with incidentalomas (bilateral, 13.1 ± 4.5 mcg/dL [p < 0.001]; unilateral, 9.7 ± 3.2 mcg/dL [p = 0.019]) than in the control subjects (7.5 ± 3.6 mcg/dL). After dexamethasone suppression test, serum cortisol levels were suppressed to less than 1.8 mcg/dL in 100% of control subjects, 33% of patients with bilateral incidentalomas, and 62% of patients with unilateral incidentalomas (p < 0.001). There were significant correlations between maximum nodule diameter on CT and serum cortisol levels after the dexamethasone suppression test (ρ = 0.500; p < 0.001) and at baseline (ρ = 0.373; p = 0.003). CONCLUSION. Increasing size of adrenal nodules is associated with more severe hyper-cortisolism and less dexamethasone suppression; these cases need further evaluation and possibly surgery because of increased risks of metabolic syndrome and cardiovascular mortality.


Assuntos
Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Neoplasias das Glândulas Suprarrenais/patologia , Hormônio Adrenocorticotrópico/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Feminino , Humanos , Hidrocortisona/sangue , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
17.
Horm Metab Res ; 52(2): 117-123, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32053843

RESUMO

Corticotroph adenomas frequently harbor somatic USP8 mutations. These adenomas also commonly exhibit underexpression of P27, a cell cycle regulator. The present study aimed to determine the influence of USP8 mutations on clinical features of Cushing's disease and to elucidate the relationship between USP8 mutations and P27 underexpression in these tumors. Retrospective study with 32 patients with Cushing's disease was followed at the Ribeirao Preto Medical School University Hospital. We evaluated the patients' clinical data, the USP8 mutation status and the gene expression of cell cycle regulators P27/CDKN1B, CCNE1, CCND1, CDK2, CDK4, and CDK6 in tumor tissue in addition to the protein expression of P27/CDKN1B. We observed somatic mutations in the exon 14 of USP8 in 31.3% of the patients. Larger tumor size was observed in patients harboring USP8 mutations (p=0.04), with similar rates of remission, age of presentation, salivary cortisol at 23:00 h and after 1 mg dexamethasone, ACTH levels, and early postoperative plasma cortisol. We observed no differences regarding the gene or protein expression of the cell cycle regulators according to USP8 mutation status. In this Brazilian series, the observed frequency of USP8 somatic mutations was similar to that reported in European ancestry populations. Although it was reasonable that USP8 mutations could contribute to cell cycle dysregulation and P27 underexpression in corticotroph adenomas, our data did not confirm this hypothesis. It is possible that increased deubiquitinase activity observed in mutated USP8 might influence other pathways related to cell growth and proliferation.


Assuntos
Adenoma Hipofisário Secretor de ACT/genética , Ciclo Celular , Endopeptidases/genética , Complexos Endossomais de Distribuição Requeridos para Transporte/genética , Hipersecreção Hipofisária de ACTH/genética , Ubiquitina Tiolesterase/genética , Adenoma Hipofisário Secretor de ACT/fisiopatologia , Adolescente , Hormônio Adrenocorticotrópico/sangue , Adulto , Brasil , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Criança , Endopeptidases/metabolismo , Complexos Endossomais de Distribuição Requeridos para Transporte/metabolismo , Éxons , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Hipersecreção Hipofisária de ACTH/metabolismo , Hipersecreção Hipofisária de ACTH/fisiopatologia , Estudos Retrospectivos , Ubiquitina Tiolesterase/metabolismo , Adulto Jovem
18.
Eur J Pharmacol ; 872: 172978, 2020 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-32014487

RESUMO

Evidences from human and animal studies indicate that exposure to infection during early life act as a stressor to impair the hypothalamic-pituitary-adrenal (HPA) axis and may be one of the contributing factors of mental illness of later life. Several atypical antipsychotic drugs (AAPDs) proved to be effective in alleviating psychiatric illness through normalization of HPA axis. However, AAPD are least tried to evaluate their efficacy in modulation of HPA axis impaired under infection. The present study elucidated that the treatment with AAPD paliperidone (PAL: 0.025 mg/kg/bw and 0.05 mg/kg/bw) during periadolescence period (postnatal day 35- postnatal day 56) dose-dependently normalized the HPA axis of the female mice who were gestationally (gestational day 15 and 17) exposed to bacterial endotoxin lipopolysaccharide (LPS: 800 µg/kg/bw; intraperitoneally). The effectiveness of PAL treatment in counteracting the LPS induced hyperactivity of HPA axis was age-related, better observed at postnatal day 120 than at postnatal day 200. The PAL modulation of HPA axis reflected at different levels: inhibition of hypothalamic CRF expression and reduction in plasma levels of adrenocorticotropin and corticosterone. Histopathological alterations such as hypertrophy and/or hyperplasia in cortical zona fasciculata as well as medullary chromaffin cells of adrenal also normalized on PAL treatment. The comparatively long wash out period after drug treatment (postnatal day 57- postnatal day 200) along with age related hormonal imbalance could be correlated to less effectiveness of PAL on HPA axis at postnatal day 200. PAL modulation of HPA axis might be through maintenance of cytokines and reproductive axis homeostasis.


Assuntos
Antipsicóticos/administração & dosagem , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Transtornos Mentais/tratamento farmacológico , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Complicações Infecciosas na Gravidez/imunologia , Efeitos Tardios da Exposição Pré-Natal/tratamento farmacológico , Adolescente , Hormônio Adrenocorticotrópico/sangue , Hormônio Adrenocorticotrópico/metabolismo , Adulto , Fatores Etários , Animais , Células Cromafins/efeitos dos fármacos , Células Cromafins/metabolismo , Corticosterona/sangue , Corticosterona/metabolismo , Hormônio Liberador da Corticotropina/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Sistema Hipotálamo-Hipofisário/fisiopatologia , Lipopolissacarídeos/imunologia , Masculino , Transtornos Mentais/sangue , Transtornos Mentais/imunologia , Transtornos Mentais/fisiopatologia , Camundongos , Palmitato de Paliperidona/administração & dosagem , Sistema Hipófise-Suprarrenal/fisiopatologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/sangue , Efeitos Tardios da Exposição Pré-Natal/imunologia , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Adulto Jovem , Zona Fasciculada/efeitos dos fármacos , Zona Fasciculada/metabolismo , Zona Fasciculada/patologia
19.
Eur J Endocrinol ; 182(2): R15-R27, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31995340

RESUMO

Glucocorticoids (GC) such as cortisol regulate multiple physiological functions, notably those involved in development, metabolism, inflammatory processes and stress, and exert their effects upon binding to the glucocorticoid receptor (GR, encoded by NR3C1 gene in humans). GC signaling follows several consecutive steps leading to target gene transactivation, including ligand binding, nuclear translocation of ligand-activated GR complexes, DNA binding, and recruitment of functional transcriptional machinery. Generalized glucocorticoid resistance syndrome, due to GR loss-of-function mutations, may be related to the impairment of one of the GC signaling steps. To date, 31 NR3C1 loss-of-function mutations have been reported in patients presenting with various clinical signs such as hypertension, adrenal hyperplasia, hirsutism or metabolic disorders associated with biological hypercortisolism but without Cushing syndrome signs and no negative regulatory feedback loop on the hypothalamic-pituitary-adrenal axis. Functional characterization of GR loss-of-function mutations often demonstrates GR haploinsufficiency and a decrease of GR target gene induction in relevant cell types. The main signs at presentation are very variable from resistant hypertension, bilateral adrenal hyperplasia likely related to increased ACTH levels but not exclusively, hirsutism to isolated renin-angiotensin-aldosterone system abnormalities in a context of 11ßHSD2 deficiency. Some mutated GR patients are obese or overweight together with a healthier metabolic profile that remains to be further explored in future studies. Deciphering the molecular mechanisms altered by GR mutations should enhance our knowledge on GR signaling and ultimately facilitate management of GC-resistant patients. This review also focuses on the criteria facilitating identification of novel NR3C1 mutations in selected patients.


Assuntos
Erros Inatos do Metabolismo/diagnóstico , Erros Inatos do Metabolismo/genética , Receptores de Glucocorticoides/deficiência , Hormônio Adrenocorticotrópico/sangue , Hormônio Adrenocorticotrópico/genética , Glucocorticoides/sangue , Glucocorticoides/genética , Humanos , Hidrocortisona/sangue , Hidrocortisona/genética , Erros Inatos do Metabolismo/sangue , Receptores de Glucocorticoides/sangue , Receptores de Glucocorticoides/genética
20.
Eur Addict Res ; 26(2): 103-108, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31940647

RESUMO

AIMS: Childhood trauma is of importance for the manifestation of substance-related disorders and maintenance of hypothalamic-pituitary-adrenal (HPA)-axis disorders. Since stress plays a crucial role in opioid compliance and craving, we investigated the immediate effects of diacetylmorphine application on the HPA axis. In particular, adrenocorticotropic hormone (ACTH) and cortisol secretion, as well as satiety regulating proopiomelanocortin peptides α-melanocyte-stimulating hormone (MSH) and ß-endorphin (END) in a cohort of opioid-dependent patients in diamorphine maintenance treatment concerning the clinical severity of their childhood trauma. METHODS: We compared the serum levels of ACTH, cortisol, MSH, and END in 15 opioid-dependent patients. All participants received treatment with diamorphine and were observed at 5 timepoints before and after injection. We split the cohort into 2 subgroups concerning childhood trauma measured by the Childhood Trauma Questionnaire. RESULTS: Splitting in 2 subgroups for mild (5) and severe trauma (10), we found that while both groups show a significant reduction of ACTH and cortisol levels over time, slopes display different progressions over time for cortisol (F[1.6] = 9.38, p = 0.02), while remaining identical for ACTH (F[1.6] = 1.69, p = 0.24). Also, levels of both MSH and END were significantly lower in severely traumatized patients. CONCLUSIONS: For the first time, we present a detailed representation of stress- and addiction-related proteins for the first 5 h after diamorphine application, demonstrating the interrelationship between stress hormones and childhood trauma as well as its potential effects on the progression of addictions such as opioid dependence.


Assuntos
Experiências Adversas da Infância , Dependência de Heroína , Heroína , Estresse Psicológico/psicologia , Ferimentos e Lesões/psicologia , Hormônio Adrenocorticotrópico/sangue , Adulto , Criança , Estudos de Coortes , Feminino , Heroína/farmacologia , Heroína/uso terapêutico , Dependência de Heroína/tratamento farmacológico , Dependência de Heroína/metabolismo , Humanos , Hidrocortisona/sangue , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/metabolismo , Masculino , Pessoa de Meia-Idade , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Sistema Hipófise-Suprarrenal/metabolismo , Inquéritos e Questionários/estatística & dados numéricos , beta-Endorfina/sangue
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