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1.
Trials ; 23(1): 4, 2022 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-34980224

RESUMO

BACKGROUND: Cardiogenic shock (CS) is a life-threatening condition characterized by circulatory insufficiency caused by an acute dysfunction of the heart pump. The pathophysiological approach to CS has recently been enriched by the tissue consequences of low flow, including inflammation, endothelial dysfunction, and alteration of the hypothalamic-pituitary-adrenal axis. The aim of the present trial is to evaluate the impact of early low-dose corticosteroid therapy on shock reversal in adults with CS. METHOD/DESIGN: This is a multicentered randomized, double-blind, placebo-controlled trial with two parallel arms in adult patients with CS recruited from medical, cardiac, and polyvalent intensive care units (ICU) in France. Patients will be randomly allocated into the treatment or control group (1:1 ratio), and we will recruit 380 patients (190 per group). For the treatment group, hydrocortisone (50 mg intravenous bolus every 6 h) and fludrocortisone (50 µg once a day enterally) will be administered for 7 days or until discharge from the ICU. The primary endpoint is catecholamine-free days at day 7. Secondary endpoints include morbidity and all-cause mortality at 28 and 90 days post-randomization. Pre-defined subgroups analyses are planned, including: postcardiotomy, myocardial infarction, etomidate use, vasopressor use, and adrenal profiles according the short corticotropin stimulation test. Each patient will be followed for 90 days. All analyses will be conducted on an intention-to-treat basis. DISCUSSION: This trial will provide valuable evidence about the effectiveness of low dose of corticosteroid therapy for CS. If effective, this therapy might improve outcome and become a therapeutic adjunct for patients with CS. TRIAL REGISTRATION: ClinicalTrials.gov , NCT03773822 . Registered on 12 December 2018.


Assuntos
COVID-19 , Choque Cardiogênico , Adulto , Humanos , Sistema Hipotálamo-Hipofisário , Estudos Multicêntricos como Assunto , Sistema Hipófise-Suprarrenal , Ensaios Clínicos Controlados Aleatórios como Assunto , SARS-CoV-2 , Choque Cardiogênico/diagnóstico , Choque Cardiogênico/tratamento farmacológico , Resultado do Tratamento
2.
Psychopharmacology (Berl) ; 239(1): 59-81, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35013761

RESUMO

RATIONALE: Depression is often associated with memory impairment, a clinical feature of Alzheimer's disease (AD), but no effective treatment is available. 7-Chloro-4-(phenylselanyl) quinoline (4-PSQ) has been studied in experimental models of diseases that affect the central nervous system. OBJECTIVES: The pharmacological activity of 4-PSQ in depressive-like behavior associated with memory impairment induced by acute restraint stress (ARS) in male Swiss mice was evaluated. METHODS: ARS is an unavoidable stress model that was applied for a period of 240 min. Ten minutes after ARS, animals were intragastrically treated with canola oil (10 ml/kg) or 4-PSQ (10 mg/kg) or positive controls (paroxetine or donepezil) (10 mg/kg). Then, after 30 min, mice were submitted to behavioral tests. Corticosterone levels were evaluated in plasma and oxidative stress parameters; monoamine oxidase (MAO)-A and MAO -B isoform activity; mRNA expression levels of kappa nuclear factor B (NF-κB); interleukin (IL)-1ß, IL-18, and IL-33; phosphatidylinositol-se-kinase (PI3K); protein kinase B (AKT2), as well as acetylcholinesterase activity were evaluated in the prefrontal cortex and hippocampus. RESULTS: 4-PSQ attenuated the depressive-like behavior, self-care, and memory impairment caused by ARS. Based on the evidence, we believe that effects of 4-PSQ may be associated, at least in part, with the attenuation of HPA axis activation, attenuation of alterations in the monoaminergic system, modulation of oxidative stress, reestablishment of AChE activity, modulation of the PI3K/AKT2 pathway, and reduction of neuroinflammation. CONCLUSIONS: These results suggested that 4-PSQ exhibited an antidepressant-like effect and attenuated the memory impairment induced by ARS, and it is a promising molecule to treat these comorbidities.


Assuntos
Quinolinas , Selênio , Acetilcolinesterase/metabolismo , Animais , Depressão/tratamento farmacológico , Hipocampo/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo , Masculino , Camundongos , Estresse Oxidativo , Sistema Hipófise-Suprarrenal/metabolismo , Quinolinas/farmacologia
3.
Endocrinology ; 163(1)2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34698826

RESUMO

PURPOSE: Sepsis is hallmarked by high plasma cortisol/corticosterone (CORT), low adrenocorticotropic hormone (ACTH), and high pro-opiomelanocortin (POMC). While corticotropin-releasing hormone-(CRH) and arginine-vasopressin (AVP)-driven pituitary POMC expression remains active, POMC processing into ACTH becomes impaired. Low ACTH is accompanied by loss of adrenocortical structure, although steroidogenic enzymes remain expressed. We hypothesized that treatment of sepsis with hydrocortisone (HC) aggravates this phenotype whereas CRH infusion safeguards ACTH-driven adrenocortical structure. METHODS: In a fluid-resuscitated, antibiotics-treated mouse model of prolonged sepsis, we compared the effects of HC and CRH infusion with placebo on plasma ACTH, POMC, and CORT; on markers of hypothalamic CRH and AVP signaling and pituitary POMC processing; and on the adrenocortical structure and markers of steroidogenesis. In adrenal explants, we studied the steroidogenic capacity of POMC. RESULTS: During sepsis, HC further suppressed plasma ACTH, but not POMC, predominantly by suppressing sepsis-activated CRH/AVP-signaling pathways. In contrast, in CRH-treated sepsis, plasma ACTH was normalized following restoration of pituitary POMC processing. The sepsis-induced rise in markers of adrenocortical steroidogenesis was unaltered by CRH and suppressed partially by HC, which also increased adrenal markers of inflammation. Ex vivo stimulation of adrenal explants with POMC increased CORT as effectively as an equimolar dose of ACTH. CONCLUSIONS: Treatment of sepsis with HC impaired integrity and function of the hypothalamic-pituitary-adrenal axis at the level of the pituitary and the adrenal cortex while CRH restored pituitary POMC processing without affecting the adrenal cortex. Sepsis-induced high-circulating POMC may be responsible for ongoing adrenocortical steroidogenesis despite low ACTH.


Assuntos
Hormônio Liberador da Corticotropina/administração & dosagem , Hidrocortisona/administração & dosagem , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Sepse/metabolismo , Hormônio Adrenocorticotrópico/metabolismo , Animais , Arginina Vasopressina/química , Corticosterona/sangue , Hipotálamo/metabolismo , Hibridização In Situ , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fenótipo , Hipófise/metabolismo , Adeno-Hipófise/metabolismo , Pró-Opiomelanocortina/química , Sepse/fisiopatologia , Transdução de Sinais
4.
Handb Exp Pharmacol ; 271: 435-452, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-33274403

RESUMO

The kappa opioid receptor (KOR)-related ligands have been demonstrated in preclinical studies for several therapeutic potentials. This chapter highlights (1) how non-human primates (NHP) studies facilitate the research and development of ligands targeting the KOR, (2) effects of the endogenous opioid peptide, dynorphin A-(1-17), and its analogs in NHP, and (3) pleiotropic effects and therapeutic applications of KOR-related ligands. In particular, synthetic ligands targeting the KOR have been extensively studied in NHP in three therapeutic areas, i.e., the treatment for itch, pain, and substance use disorders. As the KORs are widely expressed in the peripheral and central nervous systems, pleiotropic effects of KOR-related ligands, such as discriminative stimulus effects, neuroendocrine effects (e.g., prolactin release and stimulation of hypothalamic-pituitary-adrenal axis), and diuresis, in NHP are discussed. Centrally acting KOR agonists are known to produce adverse effects including dysphoria, hallucination, and sedation. Nonetheless, with strategic advances in medicinal chemistry, three classes of KOR-related agonists, i.e., peripherally restricted KOR agonists, mixed KOR/mu opioid receptor partial agonists, and G protein-biased KOR agonists, warrant additional NHP studies to improve our understanding of their functional efficacy, selectivity, and tolerability. Pharmacological studies in NHP which carry high translational significance will facilitate future development of KOR-based medications.


Assuntos
Sistema Hipotálamo-Hipofisário , Receptores Opioides kappa , Analgésicos Opioides/farmacologia , Animais , Sistema Hipotálamo-Hipofisário/metabolismo , Ligantes , Sistema Hipófise-Suprarrenal/metabolismo , Primatas/metabolismo
5.
Wiad Lek ; 74(10 pt 1): 2510-2515, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34897013

RESUMO

The aim of the study was to assess the impact of individual components of the metabolic syndrome on the human body, taking into account their etiology and pathogenesis. This article is analytical analysis of scientific and medical literature basing on aspects of the etiology and pathogenesis of the metabolic syndrome. The key role in the pathogenesis of the metabolic syndrome is played by insulin resistance, which may be a result of lifestyle conditions (low physical activity, overweight or obesity) or genetic background. A certain role in the pathogenesis of the metabolic syndrome is also attributed to disorders of the hypothalamic-pituitary-adrenal axis in the form of increased cortisol control, which may initiate the development of abdominal obesity, insulin resistance, hypertension and dyslipidemia. Aforementioned factors (environmental, hormonal and genetic) lead to excessive fat tissue gathering. The excess of abdominal fat tissue - abdominal obesity - leads to insulin resistance, the concentration of which causes body mass gain. Such mechanism is dangerous for our health and may lead to the occurrence of type 2 diabetes and premature development of atherosclerosis with all its consequences such as atherosclerotic cardiovascular diseases including coronary artery disease.


Assuntos
Diabetes Mellitus Tipo 2 , Síndrome Metabólica , Diabetes Mellitus Tipo 2/etiologia , Humanos , Sistema Hipotálamo-Hipofisário , Síndrome Metabólica/etiologia , Sistema Hipófise-Suprarrenal , Fatores de Risco
6.
Trials ; 22(1): 770, 2021 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-34736490

RESUMO

BACKGROUND: Insomnia is very common in current society, and patients are often accompanied by a certain degree of anxiety, depression, etc. Recent studies have found that the hypothalamic-pituitary-adrenal (HPA) axis excitement-inhibition state is an important indicator of sleep quality. Wrist-ankle acupuncture (WAA) is safe and effective for insomnia. Based on WAA theory, the acupressure wrist-ankle straps are portable WAA point compression straps that can treat diseases by automatically applying pressure to the treatment location and being operated by patients themselves. We design this trial to evaluate the clinical effect of the acupressure wrist-ankle strap in the treatment of mild insomnia patients with anxiety disorders. METHODS/DESIGN: This trial is a parallel-design, patients-assessor blinded, randomized, sham-controlled. In total, 114 patients diagnosed with mild insomnia and anxiety disorders will be randomly assigned into two groups, the acupressure wrist-ankle strap group or the non-acupressure wrist-ankle strap group; they will receive treatments for eight weeks with five sessions each week. Rating scales, sleep monitors, and laboratory tests will be used to observe the clinical effect. From the perspective of the circadian secretion of peripheral blood-related hormones in the hypothalamic-pituitary-adrenal (HPA) axis, the possible mechanism of acupressure wrist-ankle straps for treating insomnia is studied. DISCUSSION: The results of this study will confirm the efficacy of acupressure wrist-ankle strap in treating mild insomnia patients with anxiety disorder and whether its mechanism is related to the HPA axis. The acupressure wrist-ankle strap may become a pure physical, no side effect treatment of mild insomnia. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000039352 . Registered on 24 October 2020.


Assuntos
Acupressão , Distúrbios do Início e da Manutenção do Sono , Tornozelo , Transtornos de Ansiedade , Humanos , Sistema Hipotálamo-Hipofisário , Sistema Hipófise-Suprarrenal , Ensaios Clínicos Controlados Aleatórios como Assunto , Distúrbios do Início e da Manutenção do Sono/diagnóstico , Distúrbios do Início e da Manutenção do Sono/terapia , Resultado do Tratamento , Punho
7.
Trials ; 22(1): 833, 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34819129

RESUMO

BACKGROUND: Generalized anxiety disorder (GAD) is common among perimenopausal women. Acupuncture may be an effective treatment for GAD, but evidence is limited. The pathogenesis of GAD is not yet clear, but it is related to the hypothalamic-pituitary-adrenal axis and its excretion, cortisol (CORT), and adrenocorticotropic hormone (ACTH). The object of this study is to evaluate the efficacy of manual acupuncture (MA) versus placebo acupuncture (PA) for perimenopausal women with GAD. METHODS: This study is a single-center, randomized, single-blind clinical trial that will be conducted in the First Affiliated Hospital of Guangzhou University of Chinese Medicine. A total of 112 eligible GAD patients will be randomly assigned (1:1) to receive MA (n=56) or PA (n=56) three times per week for 4 weeks. The primary outcome measure will be the HAMA score. The secondary outcome measures will be the GAD-7 and PSQI scores and the levels of CORT and ACTH. The evaluation will be executed at baseline, 2 weeks, the end of the treatment, and a follow-up 3-month period. All main analyses will be carried out based on the intention-to-treat (ITT) principle. DISCUSSION: This study intends to compare the efficacy between MA and PA in the treatment of perimenopausal women with GAD and to further study the mechanisms underlying the effect. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100046604 . Registered on 22 May 2021.


Assuntos
Terapia por Acupuntura , Perimenopausa , Terapia por Acupuntura/efeitos adversos , Transtornos de Ansiedade , Feminino , Humanos , Sistema Hipotálamo-Hipofisário , Sistema Hipófise-Suprarrenal , Ensaios Clínicos Controlados Aleatórios como Assunto , Método Simples-Cego , Resultado do Tratamento
8.
Int J Mol Sci ; 22(21)2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-34768903

RESUMO

The hypothalamus-pituitary-adrenal (HPA) axis was described as the principal component of the stress response 85 years ago, along with the acute-phase reaction, and the defense response at the tissue level. The orchestration of these processes is essential since systemic inflammation is a double-edged sword; whereas inflammation that is timely and of appropriate magnitude is beneficial, exuberant systemic inflammation incites tissue damage with potentially devastating consequences. Apart from its beneficial cardiovascular and metabolic effects, cortisol exerts a significant immunoregulatory role, a major attribute being that it restrains the excessive inflammatory reaction, thereby preventing unwanted tissue damage. In this review, we will discuss the role of the HPA axis in the normal stress response and in critical illness, especially in critically ill patients with coronavirus disease 2019 (COVID-19). Finally, a chapter will be dedicated to the findings from clinical studies in critical illness and COVID-19 on the expression of the mediator of glucocorticoid actions, the glucocorticoid receptor (GCR).


Assuntos
COVID-19/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipotálamo-Hipofisário/virologia , Sistema Hipófise-Suprarrenal/metabolismo , Sistema Hipófise-Suprarrenal/virologia , Receptores de Glucocorticoides/metabolismo , Estado Terminal , Glucocorticoides/metabolismo , Humanos , Estresse Fisiológico
10.
Adv Exp Med Biol ; 1344: 153-168, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34773231

RESUMO

Altered behavioral rhythms are a fundamental diagnostic feature of mood disorders. Patients report worse subjective sleep and objective measures confirm this, implicating a role for circadian rhythm disruptions in mood disorder pathophysiology. Molecular clock gene mutations are associated with increased risk of mood disorder diagnosis and/or severity of symptoms, and mouse models of clock gene mutations have abnormal mood-related behaviors. The mechanism by which circadian rhythms contribute to mood disorders remains unknown, however, circadian rhythms regulate and are regulated by various biological systems that are abnormal in mood disorders and this interaction is theorized to be a key component of mood disorder pathophysiology. A growing body of evidence has begun defining how the interaction of circadian and neurotransmitter systems influences mood and behavior, including the role of current antidepressants and mood stabilizers. Additionally, the hypothalamus-pituitary-adrenal (HPA) axis interacts with both circadian and monoaminergic systems and may facilitate the contribution of environmental stressors to mood disorder pathophysiology. The central role of circadian rhythms in mood disorders has led to the development of chronotherapeutics, which are treatments designed specifically to target circadian rhythm regulators, such as sleep, light, and melatonin, to produce an antidepressant response.


Assuntos
Ritmo Circadiano , Melatonina , Animais , Humanos , Melatonina/uso terapêutico , Camundongos , Transtornos do Humor/tratamento farmacológico , Transtornos do Humor/genética , Sistema Hipófise-Suprarrenal , Sono
11.
Psychiatr Danub ; 33(Suppl 4): 463-470, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34718266

RESUMO

Depression is heterogeneous clinical entity with different clinical symptoms, that imply diverse biological underpinning, different molecular substrates and pathways. Besides different psychiatric comorbidities, depression is frequently interrelated with somatic diseases. Multi-morbidities, i.e. somatic diseases associated with depression, reduce quality of life, worsen clinical picture and increase mortality. The most frequent somatic diseases co-occurring with depression are cardiovascular and metabolic diseases. Vulnerable individuals will develop depression, and the goal in modern research and in precision/personalized medicine is to determine vulnerability factors associated with development of depression and to find easy available biomarkers of depression, especially comorbid with somatic diseases. This mini-review aimed to describe the latest published data (from 2015-20120) considering biomarkers of depression related to somatic diseases. Biomarkers related to inflammatory processes, atherosclerosis, imbalance of the hypothalamic-pituitary-adrenal axis, autonomic nerve system, sympathetic and parasympathetic nervous system, heart rate variability and endothelial dysfunction could improve the understanding of the underlying biological mechanisms of the common pathways of depression comorbid with somatic diseases. These targeted biomarkers might be used to reduce the symptoms, improve the treatment of these interrelated diseases, and decrease the morbidity and mortality.


Assuntos
Depressão , Sistema Hipotálamo-Hipofisário , Biomarcadores , Humanos , Sistema Hipófise-Suprarrenal , Qualidade de Vida
12.
Psychiatr Danub ; 33(Suppl 4): 480-485, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34718269

RESUMO

Multiple Sclerosis (MS), a chronic inflammatory neurodegenerative disease, is accompanied by a number of comorbidities. Among the psychiatric ones, depression and anxiety occupy a special place. It is estimated that the prevalence of anxiety in the MS population is 22.1% verus 13% in the general population; whereas the prevalence of anxiety levels, as determined by various questionnaires, reaches even 34.2%. Systematic literature reviews (SPL) show considerable data variations due to differences in study design, sample size, diagnostic criteria and extremely high heterogeneity (I2). Among the more conspicuous factors associated with anxiety disorder in MS are demographic factors (age and gender), nonsomatic depressive symptoms, higher levels of disability, immunotherapy treatments, MS type, and unemployment. Depression is the most common psychiatric commorbidity in MS and the lifetime risk of developing depression in MS patients is >50%. According to some research, the prevalence of depression in MS vary between 4.98% and 58.9%, with an average of 23.7% (I2=97.3%). Brain versus spinal cord lesions, as well as temporal lobe, fasciculus arcuatus, superior frontal and superior parietal lobe lesions in addition to the cerebral atrophy have been shown to be the anatomical predictors of depressive disorder in MS. Hyperactivity of the hypothalamic-pituitary-adrenal axis (HPA) and the consequent dexamethasone-insupressible hypercortisolemia, in addition to cytokine storm (IL-6, TNF-α, TGFß1, IFNγ/IL-4) present the endocrine and inflammatory basis for development of depression. Fatigue, insomnia, cognitive dysfunction, spasticity, neurogenic bladder, pain, and sexual dysfunction have shown to be additional precipitating factors in development of anxiety and depression in MS patients.


Assuntos
Esclerose Múltipla , Doenças Neurodegenerativas , Ansiedade , Transtornos de Ansiedade/epidemiologia , Depressão , Humanos , Sistema Hipotálamo-Hipofisário , Esclerose Múltipla/epidemiologia , Sistema Hipófise-Suprarrenal
13.
Transl Psychiatry ; 11(1): 523, 2021 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-34642301

RESUMO

Hypothalamic-pituitary-adrenal (HPA) axis dysregulation has been commonly reported in major depressive disorder (MDD), but with considerable heterogeneity of results; potentially due to the predominant use of acute measures of an inherently variable/phasic system. Chronic longer-term measures of HPA-axis activity have yet to be systematically examined in MDD, particularly in relation to brain phenotypes, and in the context of early-life/contemporaneous stress. Here, we utilise a temporally stable measure of cumulative HPA-axis function (hair glucocorticoids) to investigate associations between cortisol, cortisone and total glucocorticoids with concurrent measures of (i) lifetime-MDD case/control status and current symptom severity, (ii) early/current-life stress and (iii) structural neuroimaging phenotypes, in N = 993 individuals from Generation Scotland (mean age = 59.1 yrs). Increased levels of hair cortisol were significantly associated with reduced global and lobar brain volumes with reductions in the frontal, temporal and cingulate regions (ßrange = -0.057 to -0.104, all PFDR < 0.05). Increased levels of hair cortisone were significantly associated with MDD (lifetime-MDD status, current symptoms, and severity; ßrange = 0.071 to 0.115, all PFDR = < 0.05), with early-life adversity (ß = 0.083, P = 0.017), and with reduced global and regional brain volumes (global: ß = -0.059, P = 0.043; nucleus accumbens: ß = -0.075, PFDR = 0.044). Associations with total glucocorticoids followed a similar pattern to the cortisol findings. In this large community-based sample, elevated glucocorticoids were significantly associated with MDD, with early, but not later-life stress, and with reduced global and regional brain phenotypes. These findings provide important foundations for future mechanistic studies to formally explore causal relationships between early adversity, chronic rather than acute measures of glucocorticoids, and neurobiological associations relevant to the aetiology of MDD.


Assuntos
Experiências Adversas da Infância , Transtorno Depressivo Maior , Depressão , Glucocorticoides , Substância Cinzenta , Humanos , Hidrocortisona , Sistema Hipotálamo-Hipofisário , Pessoa de Meia-Idade , Sistema Hipófise-Suprarrenal
14.
PLoS One ; 16(10): e0257370, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34597314

RESUMO

BACKGROUND: The neuroendocrine stress response allows vertebrates to cope with stressors via the activation of the Hypothalamic-Pituitary-Adrenal (HPA) axis, which ultimately results in the secretion of glucocorticoids (GCs). Glucocorticoids have pleiotropic effects on behavior and physiology, and might influence telomere length dynamics. During a stress event, GCs mobilize energy towards survival mechanisms rather than to telomere maintenance. Additionally, reactive oxygen species produced in response to increased GC levels can damage telomeres, also leading to telomere shortening. In our systematic review and meta-analysis, we tested whether GC levels impact telomere length and if this relationship differs among time frame, life history stage, or stressor type. We hypothesized that elevated GC levels are linked to a decrease in telomere length. METHODS: We conducted a literature search for studies investigating the relationship between telomere length and GCs in non-human vertebrates using four search engines: Web of Science, Google Scholar, Pubmed and Scopus, last searched on September 27th, 2020. This review identified 31 studies examining the relationship between GCs and telomere length. We pooled the data using Fisher's Z for 15 of these studies. All quantitative studies underwent a risk of bias assessment. This systematic review study was registered in the Open Science Framework Registry (https://osf.io/rqve6). RESULTS: The pooled effect size from fifteen studies and 1066 study organisms shows no relationship between GCs and telomere length (Fisher's Z = 0.1042, 95% CI = 0.0235; 0.1836). Our meta-analysis synthesizes results from 15 different taxa from the mammalian, avian, amphibian groups. While these results support some previous findings, other studies have found a direct relationship between GCs and telomere dynamics, suggesting underlying mechanisms or concepts that were not taken into account in our analysis. The risk of bias assessment revealed an overall low risk of bias with occasional instances of bias from missing outcome data or bias in the reported result. CONCLUSION: We highlight the need for more targeted experiments to understand how conditions, such as experimental timeframes, stressor(s), and stressor magnitudes can drive a relationship between the neuroendocrine stress response and telomere length.


Assuntos
Glucocorticoides/sangue , Sistema Hipotálamo-Hipofisário/fisiologia , Sistema Hipófise-Suprarrenal/fisiologia , Encurtamento do Telômero , Animais , Vertebrados
15.
Rom J Morphol Embryol ; 62(1): 13-18, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34609405

RESUMO

BACKGROUND: Weather a psychological construct or a clinical entity, numerous studies have been focused on the biological link between stress, burnout, and biomarkers. AIM: The purpose of our study was to search the existing literature and summarize the immunological and endocrine alterations found in burnout patients and, also, to provide updated data for clinicians to use. METHODS: We performed a literature search in PubMed database using specific terms. RESULTS: The primary focus of the literature seems to be the hypothalamic-pituitary-adrenal (HPA) axis, which may be affected due to chronic stress, which can be investigated by measuring hormonal responsiveness [corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), cortisol, prolactin, thyroid hormones]. An important challenge that this field is faced with is the pulsatile and diurnal fluctuation of them, which may not always be considered and the heterogeneity of burnout measurements. Many studies have explored the linking pathways between the immune system and chronic stress, but only a few have specifically evaluated this process for future diagnostic or prognostic biomarkers. CONCLUSIONS: Burnout has cumulative effects on our body and stress does not affect us in a singular direction, on the contrary, significant clinical implications are found, not only microscopic, but affective symptoms leading to anxiety and depression.


Assuntos
Sistema Hipotálamo-Hipofisário , Sistema Hipófise-Suprarrenal , Hormônio Adrenocorticotrópico/metabolismo , Esgotamento Psicológico , Hormônio Liberador da Corticotropina/metabolismo , Humanos , Hidrocortisona , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipófise-Suprarrenal/metabolismo
16.
Zhen Ci Yan Jiu ; 46(8): 690-4, 2021 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-34472755

RESUMO

OBJECTIVE: To observe the clinical efficacy of Tiaoshen needling (dredging Governor Vessel and regulating mind)in the treatment of chronic insomnia (CI) and its effect on plasma melatonin (MT) and cortisol (CORT) levels, so as to explore its underlying mechanism. METHODS: Sixty patients with CI were randomly divided into the treatment group and the control group, with 30 cases in each group. Both groups were given sleep hygiene education before treatment. Patients in the treatment group received acupuncture or electroacupuncture at Baihui (GV20), Shenting (GV24), Yintang (GV29), bilateral Shenmen (HT7) and Sanyinjiao (SP6). Patients in the control group received acupuncture or electroacupuncture at bilateral Shousanli (LI10), Futu (ST32) and Feiyang(BL58). Both groups were treated every other day, 3 times a week, for a total of 4 weeks. Before and after treatment, Pittsburgh sleep quality index (PSQI) and fatigue severity scale (FSS) were used to evaluate sleep qua-lity and daytime fatigue, the plasma MT and CORT levels were measured by enzyme-linked immunosorbent assay. RESULTS: Compared with before treatment, the PSQI scores and total FSS score of the treatment group decreased significantly (P<0.01,P<0.05), and the plasma MT content increased and CORT decreased significantly in the treatment group (P<0.01),while the sleep-onset time score, sleep disturbance score and the PSQI total score of the control group decreased significantly (P<0.05). Compared with the control group, the PSQI sleep disorder score and total score, and the total FSS score as well as plasma CORT level were significantly down-regulated (P<0.01,P<0.05), while the plasma MT content was up-regulated (P<0.05) in the treatment group. CONCLUSION: Tiaoshen acupuncture can significantly improve the sleep quality of patients with CI and relieve daytime fatigue, which may be related to the increase of plasma MT content in patients with CI, thereby inhibiting the excessive activation of the hypothalamic-pituitary-adrenal axis.


Assuntos
Terapia por Acupuntura , Melatonina , Distúrbios do Início e da Manutenção do Sono , Pontos de Acupuntura , Humanos , Hidrocortisona , Sistema Hipotálamo-Hipofisário , Sistema Hipófise-Suprarrenal , Distúrbios do Início e da Manutenção do Sono/terapia , Resultado do Tratamento
17.
J Exp Biol ; 224(18)2021 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-34524449

RESUMO

The hypothalamic-pituitary-adrenal (HPA) axis controls the release of glucocorticoids, which regulate immune and inflammatory function by modulating cytokines, white blood cells and oxidative stress via glucocorticoid receptor (GR) signaling. Although the response to HPA activation is well characterized in many species, little is known about the impacts of HPA activation during extreme physiological conditions. Hence, we challenged 18 simultaneously fasting and developing elephant seal pups with daily intramuscular injections of adrenocorticotropin (ACTH), a GR antagonist (RU486), or a combination of the two (ACTH+RU486) for 4 days. We collected blood at baseline, 2 h and 4 days after the beginning of treatment. ACTH and ACTH+RU486 elevated serum aldosterone and cortisol at 2 h, with effects diminishing at 4 days. RU486 alone induced a compensatory increase in aldosterone, but not cortisol, at 4 days. ACTH decreased neutrophils at 2 h, while decreasing lymphocytes and increasing the neutrophil:lymphocyte ratio at 4 days. These effects were abolished by RU486. Despite alterations in white blood cells, there was no effect of ACTH or RU486 on transforming growth factor-ß or interleukin-6 levels; however, both cytokines decreased with the 4 day fasting progression. Similarly, ACTH did not impact protein oxidation, lipid peroxidation or antioxidant enzymes, but plasma isoprostanes and catalase activity decreased while glutathione peroxidase increased with fasting progression. These data demonstrate differential acute (2 h) and chronic (4 days) modulatory effects of HPA activation on white blood cells and that the chronic effect is mediated, at least in part, by GR. These results also underscore elephant seals' extraordinary resistance to oxidative stress derived from repeated HPA activation.


Assuntos
Sistema Hipófise-Suprarrenal , Focas Verdadeiras , Animais , Citocinas , Jejum , Hidrocortisona , Sistema Hipotálamo-Hipofisário , Contagem de Leucócitos , Estresse Oxidativo
18.
J Affect Disord ; 295: 505-512, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34509065

RESUMO

BACKGROUND: Work-related stress and burnout have become major occupational health concerns. Dysregulation of HPA axis is considered one of the central mechanisms and is potentially moderated through epigenetics. In the present study, we aim to investigate epigenetic regulation of the HPA axis in burnout, by focusing on salivary cortisol and cortisone and DNA methylation of the glucocorticoid receptor gene (NR3C1) and the serotonin transporter gene (SLC6A4). METHODS: We conducted a cross-sectional study with 59 subjects with burnout and 70 healthy controls recruited from the general population. All participants underwent a clinical interview and psychological assessment. Saliva samples were collected at 0, 30 and 60 min after awakening and were used to quantify cortisol and cortisone. Pyrosequencing was performed on whole blood-derived DNA to assess DNA methylation. RESULTS: There were no between-group differences in cortisol levels, whereas burnout participants had higher levels of cortisone. Job stress was associated with increased cortisol and cortisone. We observed both increased and decreased NR3C1 and SLC6A4 methylation in the burnout group compared to the control group. Some of these methylation changes correlated with burnout symptoms dimensionally. Increased methylation in a specific CpG in the SLC6A4 promoter region moderated the association between job stress and burnout. DNA methylation in this CpG was also associated with increased cortisol. In addition, average methylation of NR3C1 was negatively associated with cortisone levels. LIMITATIONS: This is a cross-sectional study and therefore no conclusions on causality could be made. CONCLUSIONS: We provide first evidence of changes in DNA methylation of NR3C1 and SLC6A4 in burnout, which were further associated with cortisol and cortisone. Further, increased cortisol and cortisone seemed to reflect job stress rather than burnout itself.


Assuntos
Esgotamento Psicológico/genética , Sistema Hipotálamo-Hipofisário , Sistema Hipófise-Suprarrenal , Receptores de Glucocorticoides , Proteínas da Membrana Plasmática de Transporte de Serotonina , Estudos Transversais , Metilação de DNA/genética , Epigênese Genética , Humanos , Hidrocortisona , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipófise-Suprarrenal/metabolismo , Receptores de Glucocorticoides/genética , Receptores de Glucocorticoides/metabolismo , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética
19.
Theriogenology ; 175: 89-94, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34517287

RESUMO

Cortisol (C) and dehydroepiandrosterone (DHEA) are recognized as the main fetal steroids, and they are likely to influence fetal development and have long-term effects on newborn hypothalamic-pituitary-adrenal axis (HPA) function. DHEA is often measured as its sulfates and expressed as DHEA-S. Hair analysis represents a promising methodological approach for the non-invasive measurement of steroids, allowing for a retrospective analysis of the total exposure to steroids over time, and avoiding the influence of acute events or circadian fluctuations. Hair cortisol and DHEA concentrations have been investigated in cows, but no studies have been performed on calves. The object of this study was to evaluate hair cortisol (HC) and hair DHEA-S (HDHEA-S) concentrations in beef calves from birth to six months of age. Hair samples of 12 beef calves (seven males, five females) were firstly collected at birth (T1) and then every three weeks up to six months of age (T2-T10), collecting only the re-grown hair. HC and HDHEA-S were analyzed by radioimmunoassay (RIA). Calves sex, weight and APGAR score were registered immediately after birth. Statistical analysis revealed that both HC and HDHEA-S were influenced by sampling time (P < 0.001). HC concentrations were higher at T1 compared to all subsequent samplings (T2-T10, P < 0.01); HC concentrations were higher at T2 compared to T4-T10 (P < 0.01), while no further changes were detected from T3 onward. Higher HDHEA-S concentrations were registered at T1, T2 and T3 compared to all the other samplings (P < 0.01). No correlation was found between hair concentrations of both steroids and calf sex or birthweight. APGAR score was negatively correlated only with HC at birth (P < 0.05). These data demonstrate that C and DHEA-S are quantifiable in the hair of calves and are influenced by their age. The higher HC detected at birth (T1) probably reflects the high serum C concentrations present late in pregnancy and increased by the fetal HPA axis, by which parturition is initiated in cows. The highest HDHEA-S at birth (T1) in calves indicates that the largest amounts of DHEA and its sulfates are produced during fetal development. Moreover, the findings of higher HC at three weeks after birth and of higher HDHEA-S until six weeks after birth, suggest that C and DHEA secretion continues also beyond birth, and that these steroids could be involved in the events occurring during the challenging first weeks of age in the calf.


Assuntos
Hidrocortisona , Sistema Hipotálamo-Hipofisário , Animais , Bovinos , Desidroepiandrosterona , Sulfato de Desidroepiandrosterona , Feminino , Masculino , Parto , Sistema Hipófise-Suprarrenal , Gravidez , Estudos Retrospectivos
20.
Sci Rep ; 11(1): 17929, 2021 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-34504149

RESUMO

The suprachiasmatic nucleus (SCN) functions as the central pacemaker aligning physiological and behavioral oscillations to day/night (activity/inactivity) transitions. The light signal entrains the molecular clock of the photo-sensitive ventrolateral (VL) core of the SCN which in turn entrains the dorsomedial (DM) shell via the neurotransmitter vasoactive intestinal polypeptide (VIP). The shell converts the VIP rhythmic signals to circadian oscillations of arginine vasopressin (AVP), which eventually act as a neurotransmitter signal entraining the hypothalamic-pituitary-adrenal (HPA) axis, leading to robust circadian secretion of glucocorticoids. In this work, we discuss a semi-mechanistic mathematical model that reflects the essential hierarchical structure of the photic signal transduction from the SCN to the HPA axis. By incorporating the interactions across the core, the shell, and the HPA axis, we investigate how these coupled systems synchronize leading to robust circadian oscillations. Our model predicts the existence of personalized synchronization strategies that enable the maintenance of homeostatic rhythms while allowing for differential responses to transient and permanent light schedule changes. We simulated different behavioral situations leading to perturbed rhythmicity, performed a detailed computational analysis of the dynamic response of the system under varying light schedules, and determined that (1) significant interindividual diversity and flexibility characterize adaptation to varying light schedules; (2) an individual's tolerances to jet lag and alternating shift work are positively correlated, while the tolerances to jet lag and transient shift work are negatively correlated, which indicates trade-offs in an individual's ability to maintain physiological rhythmicity; (3) weak light sensitivity leads to the reduction of circadian flexibility, implying that light therapy can be a potential approach to address shift work and jet lag related disorders. Finally, we developed a map of the impact of the synchronization within the SCN and between the SCN and the HPA axis as it relates to the emergence of circadian flexibility.


Assuntos
Relógios Circadianos/fisiologia , Ritmo Circadiano/fisiologia , Corticosterona/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo , Síndrome do Jet Lag/metabolismo , Luz , Modelos Teóricos , Sistema Hipófise-Suprarrenal/metabolismo , Jornada de Trabalho em Turnos , Núcleo Supraquiasmático/metabolismo , Animais , Biologia Computacional/métodos , Humanos , Síndrome do Jet Lag/terapia , Neurônios/metabolismo , Estimulação Luminosa/métodos , Fotoperíodo , Fototerapia/métodos , Peptídeo Intestinal Vasoativo/metabolismo
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