Chronic psychological stress exacerbates aortic medial calcification via glucocorticoids / 生理学报

Chronic psychological stress can promote vascular diseases, such as hypertension and atherosclerosis. This study aims to explore the effects and mechanism of chronic psychological stress on aortic medial calcification (AMC). Rat arterial calcification model was established by nicotine gavage in combination with vitamin D3 (VitD3) intramuscular injection, and rat model of chronic psychological stress was induced by humid environment. Aortic calcification in rats was evaluated by using Alizarin red staining, aortic calcium content detection, and alkaline phosphatase (ALP) activity assay. The expression levels of the related proteins, including vascular smooth muscle cells (VSMCs) contractile phenotype marker SM22α, osteoblast-like phenotype marker RUNX2, and endoplasmic reticulum stress (ERS) markers (GRP78 and CHOP), were determined by Western blot. The results showed that chronic psychological stress alone induced AMC in rats, further aggravated AMC induced by nicotine in combination with VitD3, promoted the osteoblast-like phenotype transformation of VSMCs and aortic ERS activation, and significantly increased the plasma cortisol levels. The 11β-hydroxylase inhibitor metyrapone effectively reduced chronic psychological stress-induced plasma cortisol levels and ameliorated AMC and aortic ERS in chronic psychological stress model rats. Conversely, the glucocorticoid receptor agonist dexamethasone induced AMC, promoted AMC induced by nicotine combined with VitD3, and further activated aortic ERS. The above effects of dexamethasone could be inhibited by ERS inhibitor 4-phenylbutyrate. These results suggest that chronic psychological stress can lead to the occurrence and development of AMC by promoting glucocorticoid synthesis, which may provide new strategies and targets for the prevention and control of AMC.

Effect of wheat-grain moxibustion on the expression of 5-HT and cortisol in the serum, and MR and GR in the hippocampus in rats with hypothyroidism complicated with depression / 中国针灸

OBJECTIVE@#To observe the effect of wheat-grain moxibustion on behavior, 5-hydroxytryptamine (5-HT) and cortisol in the serum, mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) in the hippocampus in rats with hypothyroidism complicated with depression, and to explore the possible mechanism of wheat-grain moxibustion on improving depression in rats with hypothyroidism.@*METHODS@#A total of 32 SPF SD rats were randomly divided into a blank group, a model group, a medication group and a wheat-grain moxibustion group, 8 rats in each group. Except for the blank group, the rats in the remaining groups were treated with intragastric administration of 0.1% propylthiouracil (PTU) suspension at 1 mL/100 g, once a day for 4 weeks to establish the rat model of hypothyroidism, and whether the rats were accompanied with depression-like behavior determined through behavioristics evaluation. The rats in the medication group were intervened with euthyrox at 0.9 mL/100 g, once a day, for 4 weeks; the rats in the wheat-grain moxibustion group were treated with wheat-grain moxibustion at "Dazhui" (GV 14), "Mingmen" (GV 4), "Shenshu" (BL 23) and "Pishu" (BL 20), 7 cones each acupoint, once a day, six times a week for 4 weeks. After the intervention, the depression status was observed by behavioristics test; the contents of thyroid stimulating hormone (TSH), total thyroxine (TT4), 5-HT and cortisol in the serum were detected by ELISA; the protein expressions of MR and GR in hippocampus were detected by Western blot; the expressions of MR mRNA and GR mRNA in the hippocampus were detected by real-time PCR.@*RESULTS@#Before the intervention, compared with the blank group, the scores of open field test (OFT) were decreased and the immobility time of tail suspension test (TST) was prolonged (P<0.05); the serum TSH contents were increased and TT4 contents were decreased (P<0.01) in the other three groups. After the intervention, compared with the model group, the vertical score of OFT was increased and the immobility time of forced swimming test (FST) was prolonged in the medication group (P<0.05), while the scores of three items of OFT were increased (P<0.05, P<0.01), and the immobility time of FST and TST was shortened in the wheat-grain moxibustion group (P<0.01, P<0.05). Compared with the medication group, the immobility time of TST and FST in the wheat-grain moxibustion group was shorter (P<0.05, P<0.01). Compared with the blank group, in the model group, the contents of serum TSH and cortisol were increased (P<0.01, P<0.001), while the contents of serum TT4 and 5-HT were decreased (P<0.01, P<0.001). Compared with the model group, the contents of serum TT4 and 5-HT were increased, while the contents of serum TSH and cortisol were decreased in the medication group and wheat-grain moxibustion group (P<0.01, P<0.05). Compared with the blank group, the protein and mRNA expression of MR, GR in the hippocampus in the model group was decreased (P<0.01, P<0.05, P<0.001); compared with the model group, the protein and mRNA expression of MR in the hippocampus in the medication group were increased (P<0.05), and the protein expression of MR, GR and mRNA expression of MR in the hippocampus in the wheat-grain moxibustion group were increased (P<0.05, P<0.01). Compared with the medication group, the expression of MR mRNA in the wheat-grain moxibustion group was increased (P<0.05).@*CONCLUSION@#Wheat-grain moxibustion could significantly improve thyroid function and depression in rats with hypothyroidism. Its mechanism may be related to up-regulating the protein and mRNA expression of MR and GR in the hippocampus, and then affecting the expression of serum cortisol and 5-HT.

Determinación de valores de referencia de cortisol salival en lactantes sanos de 0 a 12 meses / Determination of reference values for salivary cortisol in healthy infants aged 0-12 months

Introducción. El cortisol salival es una herramienta útil como biomarcador de estrés en pediatría, ya que la obtención de muestras no es invasiva. Hay escasa información sobre su uso en niños, y no se reportaron valores de referencia en lactantes sanos en la Argentina. Es importante establecerlos en cada centro como base para realizar estudios posteriores en lactantes, en quienes parece ser la herramienta objetiva más relevante en la actualidad para evaluar estrés. Objetivo. Determinar los valores de referencia de cortisol salival en lactantes sanos de 0 a 12 meses de edad. Métodos. Estudio descriptivo, de corte transversal, que evaluó cortisol salival matutino de niños sanos de ambos sexos de 0 a 12 meses que concurrieron a control de salud en el Hospital Pirovano entre marzo de 2017 y marzo de 2018. Se tomaron muestras de saliva de 8 a 9 a. m. en ayunas y se procesaron con electroquimioluminiscencia. Los resultados se informaron como media y desvío estándar. Resultados. Se incluyeron 140 niños, y se obtuvieron 96 muestras. La media de cortisol salival matutino fue 5,46 nmol/l (intervalo de confianza del 95 %: 4,66-6,38), desvío estándar 2,15. No se observó correlación con la variable edad, por lo cual el intervalo de referencia no requirió el fraccionamiento por grupo etario. No se observaron diferencias significativas respecto a sexo, edad gestacional, peso al nacer, tipo de parto o tipo de alimentación. Conclusión. Se informó el intervalo de referencia de cortisol salival matutino en lactantes sanos de 0 a 12 meses.

Introduction. Salivary cortisol is a useful tool as a biomarker of stress in pediatrics because it allows for non-invasive sampling. There is little information about its use in children, and no reference values for healthy infants have been reported in Argentina. Reference values should be established at each site as the basis for subsequent tests in infants, for whom salivary cortisol appears to be the most relevant objective tool to assess stress at present. Objective. To determine reference values for salivary cortisol in healthy infants aged 0-12 months. Methods. Descriptive, cross-sectional study that assessed morning salivary cortisol levels in healthy male and female infants aged 0-12 months that attended Hospital Pirovano for a health checkup between March 2017 and March 2018. Fasting saliva samples were collected between 8 and 9 a.m. and were processed using electrochemiluminescence. Results were reported as mean and standard deviation. Results. A total of 140 infants were included, and 96 samples were collected. Mean morning salivary cortisol levels were 5.46 nmol/L (95 % confidence interval: 4.66-6.38), standard deviation: 2.15. No correlation to age was observed, so it was not necessary to divide the reference range into age groups. No significant differences were observed in terms of sex, gestational age, birth weight, type of delivery or type of feeding. Conclusion. The reference range of morning salivary cortisol levels in healthy infants aged 0-12 months was reported.

Evaluation of BDNF levels in patients hospitalized for physical trauma at an emergency hospital in Porto Alegre, southern Brazil / Avaliação dos níveis de BDNF em pacientes hospitalizados por trauma físico em um hospital de emergência de Porto Alegre, sul do Brasil

Abstract Objective To assess the association between brain-derived neurotrophic factor (BDNF) levels and acute stress disorder (ASD) in patients who have suffered physical trauma. Methods Data were collected at an emergency hospital in Porto Alegre, state of Rio Grande do Sul, southern Brazil. Participants were over 18 years of age, victims of physical trauma, and had been hospitalized for a minimum of 48 hours. A total of 117 hospitalized patients who agreed to participate in the research were grouped according to the shift in which blood was collected (38 subjects from the morning shift and 79 from the afternoon shift), had their BDNF levels measured and responded to other questionnaires. Respondents were further grouped by age into three ranges: 18-30, 31-50 and 51-70 years. Results We found a significant difference in the distribution of BDNF between the two shifts in which blood samples were collected, with the afternoon group having higher BDNF levels (U = 1906.5, p = 0.018). A difference was observed only between the 18-30 group and the 51-70 group in the afternoon shift (Umorning = 1107, pmorning = 0.575; Uafternoon = 7175, pafternoon = 0.028). Conclusions The population whose blood samples were collected in the afternoon showed significantly higher values of BDNF compared to those of the morning shift. This same population presented lower BDNF levels when associated with ASD subtypes A1, A2, and A. We hypothesize that the lower values of BDNF measured in the morning shift were due to a response to the circadian cycle of cortisol, whose action inhibits the expression of serum neurotrophins.

Resumo Objetivo Verificar a associação entre os níveis de fator neurotrófico derivado do cérebro (brain-derived neurotrophic factor [BDNF]) e transtorno de estresse agudo (TEA) em pacientes que sofreram trauma físico. Métodos Os dados foram coletados em um hospital de emergência de Porto Alegre, Rio Grande do Sul, Brasil. Os participantes eram maiores de 18 anos, vítimas de trauma físico e estavam hospitalizados por um período mínimo de 48 horas. Um total de 117 pacientes hospitalizados que concordaram em participar da pesquisa foram agrupados de acordo com o turno de realização da coleta de sangue (38 sujeitos no turno da manhã e 79 sujeitos no turno da tarde), tiveram seus níveis de BDNF medidos e responderam a outros questionários. Os entrevistados também foram agrupados por idade em três faixas etárias: 18-30, 31-50 e 51-70 anos. Resultados Encontramos uma diferença significativa na distribuição de BDNF entre os turnos, sendo que o grupo da tarde apresentou níveis maiores de BDNF (U = 1906,5, p = 0,018). Houve diferença entre o grupo de 18-30 anos e o de 51-70 anos no turno da tarde (Umanhã = 1107, pmanhã = 0,575; Utarde = 7175, ptarde = 0,028). Conclusões A população cuja coleta ocorreu à tarde apresentou valores significativamente maiores de BDNF em relação à coleta do turno da manhã. Esta mesma população apresentou menores níveis dessa neurotrofina quando associada com os subtipos A1, A2 e A de TEA. É possível hipotetizar que os menores valores de BDNF aferidos na coleta do turno da manhã se devam a uma resposta ao ciclo circadiano do cortisol, cuja ação inibe a expressão de neurotrofinas séricas.

Can physical exercise modulate cortisol level in subjects with depression? A systematic review and meta-analysis / O exercício físico pode modular os níveis de cortisol em indivíduos com depressão? Uma revisão sistemática e metanálise

Abstract Introduction: Major depressive disorder (MDD) is a prevalent medical illness that is associated with chronic stress. Patients with MDD can show an imbalance in cortisol levels, which can be restored with the remission of symptoms. Physical exercise training has been used as a tool to promote changes in cortisol levels in healthy individuals. However, it is unknown if exercise can produce the same results in individuals with MDD. Objective: To review evidence of cortisol changes after exercise training in individuals with MDD. Methods: We conducted a search on PubMed, SciELO, LILACS, ISI Web of Knowledge, Scopus, and PsycInfo databases. Random effects meta-analysis was performed and standardized mean difference (SMD) effect size was calculated. Analyses of forest and funnel plots was conducted using Stata v.11.0 software. Results: At first, 463 studies were obtained in the search. After completion of the selection procedure, five articles with seven analyses were included. Type of exercise, frequency of training, cortisol measurement, and type of control group were analyzed. There was a reduction of cortisol levels in the exercise group (SMD = −0.65, 95%CI 1.30-0.01). Moreover, sensitivity analysis and subgroup analyses revealed an effect of type (aerobic exercise) and frequency (five times per week) of exercise on reduction of cortisol levels. However, these results should be interpreted cautiously due to the small number of studies and a substantial heterogeneity among them. Conclusion: Physical exercise promotes a reduction in cortisol levels in individuals with MDD. However, this finding can be influenced by type of exercise, weekly frequency, and type of cortisol measurement.

Resumo Introdução: A depressão maior (DM) é uma doença associada ao estresse crônico que pode apresentar um desequilíbrio nos níveis de cortisol, podendo ser recuperado com a remissão dos sintomas. O exercício tem sido utilizado como uma ferramenta para promover mudanças nos níveis de cortisol em indivíduos saudáveis. No entanto, não se sabe se o exercício produz os mesmos resultados em indivíduos com DM. Objetivo: Revisar evidências de alterações dos níveis de cortisol após o exercício em indivíduos com DM. Métodos: Foi realizada busca nas bases de dados PubMed, SciELO, LILACS, ISI Web of Knowledge, Scopus e PsycInfo. Procedeu-se a metanálise com o cálculo do tamanho do efeito da diferença de média padronizada. Foi utilizado o software Stata v.11.0. Resultados: Foram obtidos na busca 463 estudos. Após o procedimento de seleção, cinco artigos com sete análises foram incluídos. O tipo de exercício, frequência de treinamento, tipo de medida do cortisol e tipo de grupo controle foram analisados como subgrupos. Houve uma redução dos níveis de cortisol no grupo de exercício. Além disso, a análise de sensibilidade e análises de subgrupos revelaram um efeito do tipo (exercício aeróbico) e da frequência (cinco vezes por semana) de exercício na redução dos níveis de cortisol. No entanto, esses resultados devem ser interpretados com cautela, devido ao pequeno número de estudos e uma heterogeneidade substancial entre eles. Conclusão: O exercício promove redução dos níveis de cortisol em indivíduos com DM. No entanto, esse achado pode ser influenciado pelo tipo de exercício, medida do cortisol e frequência semanal.

Salivary cortisol during memory encoding in pregnancy predicts postpartum depressive symptoms: a longitudinal study / Cortisol salivar durante aquisição de memória na gravidez prediz sintomas depressivos no período pós-parto: um estudo longitudinal

Abstract Introduction Postpartum depression (PPD) is a common disorder that substantially decreases quality of life for both mother and child. In this longitudinal study, we investigated whether emotional memory, salivary cortisol (sCORT) or alpha-amylase during pregnancy predict postpartum depressive symptoms. Methods Forty-four pregnant women (14 euthymic women with a diagnosis of major depressive disorder [MDD] and 30 healthy women) between the ages of 19 and 37 years (mean age = 29.5±4.1 years) were longitudinally assessed in the 2nd trimester of pregnancy (12-22 weeks of gestational age) and again at 14-17 weeks postpartum. Depressive symptoms were assessed using the Edinburgh Postnatal Depression Scale (EPDS). Results Follow-ups were completed for 41 women (7% attrition). Postpartum EPDS scores were predicted by sCORT collected immediately after an incidental encoding memory task during pregnancy (b=-0.78, t -2.14, p=0.04). Postpartum EPDS scores were not predicted by positive (p=0.27) or negative (p=0.85) emotional memory. Conclusions The results of this study indicate that higher levels of sCORT during a memory encoding task in the 2nd trimester of pregnancy are associated with lower postpartum EPDS scores. While the hypothalamus-pituitary-adrenal (HPA) axis has long been associated with the neurobiology of MDD, the role of the HPA axis in perinatal depression deserves more attention.

Resumo Introdução A depressão pós-parto é um transtorno prevalente que afeta negativamente a qualidade de vida da mãe e da criança. Neste estudo longitudinal, nós investigamos se a memória emocional, o cortisol salivar (salivary cortisol, sCORT) ou alfa-amilase durante a gravidez predizem sintomas depressivos no período pós-parto. Métodos Um total de 44 mulheres grávidas [14 eutímicas com diagnóstico de transtorno depressivo maior (TDM) e 30 voluntárias sadias] entre 19 e 37 anos de idade (idade média = 29.5±4.1 anos) foram avaliadas longitudinalmente no 2° trimestre da gravidez (12-22 semanas de gestação) e na 1417ª semana pós-parto. Sintomas depressivos foram avaliados com a Escala de Depressão Pós-Natal de Edimburgo (Edinburgh Postnatal Depression Scale, EPDS). Resultados Quarenta e uma mulheres completaram o seguimento (7% de perda). sCORT coletado imediatamente antes de um teste de aquisição memória durante a gravidez foi preditor dos escores da escala EPDS no período pós-parto (b=-0.78, t -2.14, p=0.04). Memória emocional positiva (p=0.27) ou negativa (p=0.85) não foram preditores dos escores da escala EPDS no período pós-parto. Conclusão Os resultados deste estudo indicam que altos níveis de sCORT durante um teste de aquisição de memória no 2° trimestre da gravidez foram associados com baixos escores na escala EPDS no período pós-parto. Uma vez que o eixo hipotálamo-hipófise-adrenal (HHA) tenha sido envolvido na neurobiologia do TDM, o papel do eixo HHA na depressão perinatal merece mais atenção.

Perspectivas dos estudos sobre violência na adolescência e cortisol: revisão bibliográfica sistemática / Prospects of studies on violence, adolescence and cortisol: a systematic literature review

Resumo A violência afeta negativamente a saúde de crianças e adolescentes, impactando sua qualidade de vida. Provoca estresse e exige da vítima uma capacidade adaptativa, o que pode acarretar mudanças psicológicas e biológicas. Os níveis do hormônio cortisol têm sido utilizados como biomarcador de estresse em vários estudos. Este artigo se propõe a realizar uma revisão bibliográfica sistemática das publicações sobre cortisol e violência envolvendo adolescentes no período de 2000 a 2013. Os seguintes descritores foram usados: "violência", "adolescente" e "cortisol", "violence, "adolescent", cortisol", que incluiu as bases bibliográficas PubMed/Medline, Lilacs, BVS e SciELO. Foram analisados 12 artigos. A maior parte dos estudos envolve participantes dos Estados Unidos, de ambos os sexos e sem grupo controle. Diferentes tipos de violência são estudados, destacando-se a familiar, vitimização ou testemunho. Todos utilizaram a saliva para medição do cortisol. Não existe uma padronização metodológica para a análise. A maior parte dos estudos (83,3%) encontrou associação estatisticamente significativa entre o nível de cortisol e a exposição à violência. Ainda não existe uniformidade nos resultados encontrados, seja quanto ao sexo, tipo de violência, condição socioeconômica ou forma de análise de cortisol.

Abstract Violence has a negative impact on adolescents and affects their quality of life. It causes stress and requires the victim's adaptive capacity, which can cause psychological and biological changes. Hormone cortisol levels have been used as stress biomarker in several studies. This paper aims to perform a systematic literature review of publications on cortisol and violence involving teenagers from 2000 to 2013. Descriptors "cortisol", "violence" and "adolescent" were used in both English and Portuguese in this review, which included bibliographic databases PubMed/Medline, Lilacs, BVS and SciELO. Twelve papers were analyzed. Most studies involve participants from the United States, of both genders and without a control group. Different types of violence are studied, especially family violence, victimization or testimony. All studies used saliva to measure cortisol and no standard methodology was used for the analysis. Most studies (83.3%) found a statistically significant association between cortisol levels and exposure to violence. Results regarding gender, type of violence, socioeconomic status or cortisol analysis methods are not yet uniform.

Salivary cortisol and alpha-amylase: subclinical indicators of stress as cardiometabolic risk

Currently, the potential for cardiovascular (CV) stress-induced risk is primarily based on the theoretical (obvious) side effects of stress on the CV system. Salivary cortisol and α-amylase, produced respectively by the hypothalamus-pituitary-adrenal (HPA) axis and the sympathetic-adrenomedullary (SAM) system during stress response, are still not included in the routine evaluation of CV risk and require additional and definitive validation. Therefore, this article overviews studies published between 2010 and 2015, in which salivary cortisol and α-amylase were measured as stress biomarkers to examine their associations with CV/CMR (cardiometabolic risk) clinical and subclinical indicators. A comprehensive search of PubMed, Web of Science and Scopus electronic databases was performed, and 54 key articles related to the use of salivary cortisol and α-amylase as subclinical indicators of stress and CV/CMR factors, including studies that emphasized methodological biases that could influence the accuracy of study outcomes, were ultimately identified. Overall, the biological impact of stress measured by salivary cortisol and α-amylase was associated with CV/CMR factors. Results supported the use of salivary cortisol and α-amylase as potential diagnostic tools for detecting stress-induced cardiac diseases and especially to describe the mechanisms by which stress potentially contributes to the pathogenesis and outcomes of CV diseases.

Stress and Cognitive Reserve as independent factors of neuropsychological performance in healthy elderly / Estresse e Reserva Cognitiva como determinantes independentes para o desempenho neuropsicológico de idosos saudáveis

Abstract Exposure to high levels of cortisol and self-reported stress, as well as cognitive reserve, have been linked to Alzheimer’s disease pathology. However, there are no studies on the interaction of these variables. The present study aims to assess the associations of measures of cortisol, self-reported stress, and cognitive reserve with neuropsychological performance in healthy elderly people; besides, to test the interactions between these variables. Cross-sectional analyzes were conducted using data on stress, cognitive reserve and clinical conditions in 145 healthy elderly adults. A neuropsychological battery was used to assess executive functions, verbal memory and processing speed. Measurement of salivary cortisol at the circadian nadir was taken. A negative association between different stress measures and performance on tasks of memory, executive functions and processing speed was observed. Elderly people with higher cognitive reserve showed superior performance on all neuropsychological measures. No significant interaction between stress and cognitive reserve to neuropsychological performance was observed. These results indicate that older adults with high levels of stress and reduced cognitive reserve may be more susceptible to cognitive impairment.

Resumo A exposição a níveis elevados de cortisol e de estresse psicológico, assim como à reserva cognitiva, têm sido relacionadas a sintomas da Doença de Alzheimer. Contudo, não há estudos sobre a interação dessas variáveis. Objetivamos examinar as associações de medidas de cortisol e estresse psicológico e de reserva cognitiva com o desempenho neuropsicológico de idosos saudáveis, além de analisar a existência de interações entre essas variáveis. Análises transversais foram conduzidas usando dados sobre estresse, reserva cognitiva e condições clínicas em 145 idosos saudáveis. Usamos uma bateria neuropsicológica para medir as funções executivas, memória verbal e velocidade de processamento. Utilizamos uma medida de cortisol salivar para o nadir circadiano. Encontramos uma associação negativa entre diferentes medidas de estresse e o desempenho em tarefas de memória, funções executivas e velocidade de processamento. Idosos com elevada reserva cognitiva apresentaram um desempenho superior em todas as medidas neuropsicológicas. Não houve interação significativa entre estresse e Reserva Cognitiva para o desempenho neuropsicológico. Estes resultados sugerem que idosos com níveis elevados de estresse e reduzida reserva cognitiva podem ser mais suscetíveis ao comprometimento cognitivo.

Imbalance in the diurnal salivary testosterone/cortisol ratio in men with severe obstructive sleep apnea: an observational study / Desequilíbrio na proporção salivar diurna de testosterona/cortisol em homens com apneia obstrutiva do sono grave: um estudo observacional

ABSTRACT INTRODUCTION: The complex relationship between sleep disorders and hormones could lead to alterations in the production of cortisol and testosterone in obstructive sleep apnea (OSA) patients. OBJECTIVE: The purpose of this study was to determine the diurnal trajectories of salivary free-testosterone, free-cortisol and their ratio (T/C). METHODS: Ten subjects newly diagnosed with OSA, based on nocturnal polysomnography evaluation and excessive daytime sleepiness, and seven matched controls were consecutively recruited. Cortisol and testosterone were measured in salivary samples collected upon awakening, at noon and in the evening. The psychometric evaluation of anxiety/depression and referred sexual function disturbances was performed to evaluate the presence of neuropsychological comorbidities. RESULTS AND CONCLUSION: The main finding was that OSA subjects displayed hypocortisolism upon awakening and a significant reduction in testosterone concentration in the evening in comparison with the control group, which has maintained the physiological testosterone and cortisol diurnal fluctuation, with higher hormone concentrations in the morning and lower concentrations in the evening. The use of data from multiple diurnal measurements rather than a single point allowed the detection of T/C ratio changes of opposite signs at the beginning and end of the day: the OSA subjects had a higher T/C ratio than the controls in the morning, while their T/C ratio was significantly lower than that of the controls in the evening. The imbalances in the anabolic-catabolic diurnal equilibrium suggest that OSA is associated with a dysregulation of the hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal axes, potentially an underlying cause of some of the neuropsychological comorbidities observed in OSA patients.

Resumo Introdução: A relação complexa entre os distúrbios do sono e os hormônios pode levar a alterações na produção de cortisol e testosterona em pacientes com Apneia obstrutiva do sono (AOS). Objetivo: O objetivo deste estudo foi determinar as curvas diurnas de testosterona e cortisol livres na saliva e sua proporção (razão T/C). Método: Dez indivíduos recém-diagnosticados com AOS com base na avaliação por polissonografia noturna e sonolência diurna excessiva e sete controles pareados foram recrutados, consecutivamente. Cortisol e testosterona foram medidos em amostras de saliva coletadas ao acordar, ao meio-dia e à noite. A avaliação psicométrica dos distúrbios de ansiedade/depressão e função sexual mencionados foi realizada para detectar a presença de comorbidades neuropsicológicas. Resultados: O achado principal foi que os indivíduos com AOS apresentam hipocortisolismo ao acordar e uma redução significante na concentração de testosterona à noite, em comparação com o grupo controle, que manteve a variação fisiológica diurna de testosterona e cortisol com concentrações hormonais mais elevadas pela manhã e concentrações mais baixas durante a noite. O uso de dados de várias mensurações diurnas, em vez de uma única mensuração, permitiu detectar as alterações na razão T/C de sinais opostos no início e no final do dia: os indivíduos com AOS apresentaram razão T/C maior que os controles na parte da manhã, enquanto que a razão T/C foi significantemente inferior à dos controles durante a noite. Conclusão: Os desequilíbrios no balanço anabólico-catabólico diurno sugerem que a AOS está associada a uma desregulação dos eixos hipotálamo-hipófise-adrenal e hipotálamo-hipófise-gonadal, potencialmente a causa subjacente de algumas das comorbidades neuropsicológicas observadas em pacientes com AOS.

Relationship among Periodontal Disease, Insulin Resistance, Salivary Cortisol, and Stress Levels during Pregnancy

Abstract Pregnancy is a period involving important metabolic changes that enable the maintenance of the mother's health and development of the fetus. This study aimed to assess the relationship among periodontal disease, insulin resistance, salivary cortisol concentration and level of perceived stress in pregnant women. This was a cross-sectional study. The sample comprised 96 pregnant women between the fifth and seventh month of pregnancy registered at the Basic Health Units of the Unified Health System (SUS). The periodontal condition was assessed after obtainment free and informed consent from the participants. Participants were divided into three groups: control subjects with a healthy periodontal condition (CN; n=46), patients with gingivitis (GI; n=26), and patients with periodontitis (PI; n=24). Saliva and blood samples were collected for evaluation of salivary cortisol concentration, glycemia, insulinemia and Homeostasis Model Assessment-Insulin Resistance index. A validated survey for the assessment of perceived stress levels was also performed. PI group showed significantly higher (p<0.05) blood glucose levels (CN: 4.43±0.05; GI: 4.46±0.04; PI: 4.68±0.08), insulinemy (CN: 6.93±0.45; GI: 8.87±0.79; PI: 12.77±1.30), insulin resistance (CN: 1.40±0.10; GI: 1.81±0.18; PI: 2.66±0.29) compared with the CN and GI groups. The levels of perceived stress were higher (p<0.05) in PI and GI groups when compared to CN group (CN: 20.5±1.26; GI: 25.8±1.95; PI: 26.6±1.36). There was no significant difference in the concentration of salivary cortisol between the groups (CN: 11.13±0.58; GI: 11.96±0.74; PI: 11.47±0.74). It was concluded that there is a relationship between higher levels of perceived stress, insulin resistance and the occurrence of periodontal disease during pregnancy. This study emphasizes the importance of preventing periodontitis in order to avoid insulin resistance and stress during pregnancy since these can cause systemic complications for the mother and the fetus.

Resumo A gravidez é um período que envolve alterações metabólicas importantes que permitem a manutenção da saúde e desenvolvimento fetal e materno. Este estudo teve como objetivo avaliar a relação entre doença periodontal, resistência à insulina, concentração de cortisol salivar e nível de estresse percebido em gestantes. Trata-se de um estudo transversal. A amostra foi composta por 96 gestantes entre o quinto e sétimo mês, registradas em Unidades Básicas de Saúde do Sistema Único de Saúde. A condição periodontal foi avaliada após a obtenção do consentimento livre e esclarecido das participantes. As participantes foram divididas em três grupos: pacientes controle com condição periodontal saudável (CN; n=46), com gengivite (GI; n=26) e com periodontite (PI; n=24). As amostras salivares e sanguíneas foram coletadas para avaliação da concentração salivar de cortisol, glicemia, insulinemia e índice HOMA-IR. Foi aplicado um questionário validado para verificação dos níveis de estresse percebido. Grupo PI apresentou níveis significativamente mais elevados (p<0,05) de glicose no sangue (CN: 4,43±0,05; GI: 4,46±0,04; PI: 4,68±0,08), insulinemia (CN: 6,93±0,45; GI: 8,87±0,79; PI: 12,77±1,30), resistência à insulina (CN: 1,40±0,10; GI: 1,81±0,18; PI: 2,66±0,29) em comparação com os grupos CN e GI. Os níveis de estresse percebido foram maiores (p<0,05) nos grupos PI e GI quando comparados ao grupo CN (CN: 20,5±1,26; GI: 25,8±1,95; PI: 26,6±1,36). Não houve diferença significativa na concentração de cortisol salivar entre os grupos (CN: 11,13±0,58; GI: 11,96±0,74; PI: 11,47±0,74). Concluiu-se que há uma relação entre os níveis mais elevados de estresse percebido, resistência à insulina e ocorrência da doença periodontal durante a gravidez. Este estudo enfatiza a importância de prevenir a periodontite, a fim de evitar a resistência à insulina e estresse durante a gravidez, uma vez que estes podem causar complicações sistêmicas para a mãe e para o feto.

Alterações no cortisol salivar e doença periodontal / Salivary cortisol changes and periodontal disease

O objetivo deste trabalho foi verificar na literatura possíveis interações entre doença periodontal, patologia de caráter infeccioso e altamente prevalente na população adulta brasileira, e o cortisol salivar através de uma revisão da literatura. Foram pesquisados artigos científicos nas bases de dados Scielo e PubMed, a partir do ano de 2002. Foram excluídos artigos científicos sobre pesquisas experimentais e que não estivessem redigidos em português ou inglês. Através da revisão da literatura, foi possível aclarar as relações entre estresse, cortisol e doença periodontal, que parecem ocorrer através da ativação do eixo hipotálamo-pituitária adrenal e pela ativação do sistema nervoso autônomo. Isto gera alterações no padrão imunológico do paciente, pela liberação e ativação de catecolaminas, citocinas e outros mediadores da inflamação, fazendo com que o paciente se torne mais suscetível à doença periodontal. Além disto, também foi verificado que o cortisol, dependendo de sua concentração, pode favorecer o crescimento de patógenos periodontais. Finalmente, a maioria dos trabalhos avaliados revela uma correlação positiva entre estresse e doença periodontal, que pode ser útil na avaliação clínica destes pacientes. Porém, ainda faltam estudos longitudinais para aumentar a evidência científica clínica e alinhar a metodologia das pesquisas nesta área.

The aim of this study was to assess in the literature possible interactions between periodontal disease, an infectious pathology and highly prevalent in the adult Brazilian population, and salivary cortisol, through a literature review. Scientific articles were searched in PubMed and Scielo databases from 2002 to 2015. Papers on experimental research and not written in the English language were excluded. It was possible to clarify the relationship between stress, cortisol and periodontal disease, which seem to occur through activation of the hypothalamic-pituitary-adrenal axis and the activation of the autonomic-nervous system. This leads to changes in the patient's immune system, by release and activation of catecholamine, cytokines and other infl ammation mediators, making the patient more susceptible to periodontal disease. In addition, it was also found that cortisol, depending on its concentration, may upregulate the growth of periodontal pathogens. Finally, most of the evaluated studies showed a positive correlation between stress and periodontal disease, which can be useful in the clinical evaluation of these patients. However, longitudinal studies are lacking to increase the clinical scientific evidence and align the research methods in this area.

Hair cortisol in drug-naïve first-episode individuals with psychosis

Objectives: To compare hair cortisol concentrations (HCC) in drug-naïve first-episode psychosis (FEP) patients and healthy controls and to investigate the correlations between HCC and psychopathology. Methods: Twenty-four drug-naïve FEP patients and 27 gender- and age-matched healthy control subjects were recruited. The Structured Clinical Interview for DSM-IV (SCID-1) was used to confirm/rule out diagnoses, and the Positive and Negative Symptoms Scale (PANSS) was used to assess symptom severity. Hair samples (2-3 cm long) obtained from the posterior vertex region of the scalp were processed in 1-cm segments considering a hair growth rate of 1 cm per month. The 1-cm segments were classified according to their proximity to the scalp: segment A was the closest to the scalp and referred to the month prior to inclusion in the study. Segments B and C referred to the 2nd and 3rd months prior to the time of evaluation respectively. Hair steroid extraction was performed using a known protocol. Results: Two-way analysis of covariance (ANCOVA) with gender and age as covariates revealed a group effect (F1.106 = 4.899, p = 0.029) on HCC. Between-segment differences correlated with total PANSS score and with PANSS General Psychopathology subscale and total score. Conclusions: Our findings suggest that hypothalamic-pituitary-adrenal (HPA) axis, as assessed by long-term (3-month) cortisol concentration, is abnormal in the early stages of psychosis. The magnitude of changes in HCC over time prior to the FEP correlates to psychopathology. HPA axis abnormalities might begin prior to full-blown clinical presentation requiring hospital admission.

Effect of (+)-dehydrofukinone on GABAA receptors and stress response in fish model

(+)-Dehydrofukinone (DHF) is a major component of the essential oil of Nectandra grandiflora (Lauraceae), and exerts a depressant effect on the central nervous system of fish. However, the neuronal mechanism underlying DHF action remains unknown. This study aimed to investigate the action of DHF on GABAA receptors using a silver catfish (Rhamdia quelen) model. Additionally, we investigated the effect of DHF exposure on stress-induced cortisol modulation. Chemical identification was performed using gas chromatography-mass spectrometry and purity was evaluated using gas chromatography with a flame ionization detector. To an aquarium, we applied between 2.5 and 50 mg/L DHF diluted in ethanol, in combination with 42.7 mg/L diazepam. DHF within the range of 10-20 mg/L acted collaboratively in combination with diazepam, but the sedative action of DHF was reversed by 3 mg/L flumazenil. Additionally, fish exposed for 24 h to 2.5-20 mg/L DHF showed no side effects and there was sustained sedation during the first 12 h of drug exposure with 10-20 mg/L DHF. DHF pretreatment did not increase plasma cortisol levels in fish subjected to a stress protocol. Moreover, the stress-induced cortisol peak was absent following pretreatment with 20 mg/L DHF. DHF proved to be a relatively safe sedative or anesthetic, which interacts with GABAergic and cortisol pathways in fish.

Fecal cortisol metabolites as indicators of stress in crab-eating-fox (Cerdocyoun thous) in captivity / Metabolitos fecais de cortisol como indicadores de estresse em cachorro-do-mato (Cerdocyoun thous) em cativeiro

Blood samples collection is a common method in biological research using domestic animals. However, most blood sampling techniques are complicated and highly invasive and may therefore not be appropriate for wildlife animals in research concerning stress. Thus, a non-invasive method to measure steroid hormones is critically needed. The first goal of this study was to determine how glucocorticoids concentrations are impacted by translocation and reproductive activity in crab-eating-fox (Cerdocyoun thous) in captivity. The physiological relevance of fecal glucocorticoid metabolites was further validated by demonstrating: (1) The translocation of a male to a females enclosure resulted in a 3.5-fold increase compared to baseline concentrations, (2) changes in adrenocortical activity, as reflected in concentrations of fecal cortisol metabolites during reproduction, gestation and lactation in females foxes, indicating that social interactions resulted in large increases of fecal glucocorticoids metabolites during the reproductive season. From these findings we conclude that fecal samples can be used for the non-invasive assessment of adrenocortical status in crab-eating-fox...

Coleta de sangue é um método comumente utilizado na pesquisa com animais domésticos. Entretanto, a técnica de coleta de sangue torna-se complicada e altamente invasiva em animais selvagens devido ao estresse, tornando-a inapropriada para pesquisa. Dessa maneira, métodos não invasivos utilizados na mensuração de hormonios tornam-se necessários. O principal objetivo deste estudo foi determinar como as concentrações de glucocorticoides atuam durante a translocação e a atividade reprodutiva de cachorro-do-mato (Cerdocyoun thous) em cativeiro. A relevância fisiológica da análise de metabolitos fecais de glucocorticoides pôde ser validada pela demonstração de que: (1) A translocação de machos para o recinto de fêmeas resultou em um aumento de 3.5 vezes comparado a concentrações basais; (2) mudanças na atividade adrenocortical, como reflexo das concentrações de metabolitos de cortisol fecal durante a reprodução, gestação e lactação em femeas de cachorro-do-mato (Cerdocyoun thous), indicaram que interações sociais resultaram em aumento de glucocorticoides fecais durante a época reprodutiva. Com estas constatações podemos concluir que amostras fecais podem ser usadas para acesso não invasivo da atividade adrenocortical em cachorro-do-mato (Cerdocyoun thous)...

Reconhecimento materno na Unidade de Cuidado Intensivo Neonatal / Reconocimiento materno en la Unidad de Cuidado Intensivo Neonatal / Mother recognition in the Neonatal Intensive Care Unit

RESUMO Objetivo: analisar experiências maternas em Unidade de Cuidado Intensivo Neonatal, com foco nas relações de reconhecimento. Método: estudo qualitativo, desenvolvido na perspectiva da hermenêutica gadameriana, fundamentado no conceito honnethiano de reconhecimento. Foram entrevistadas, em profundidade, dez mães de crianças internadas em Unidade de Cuidado Intensivo Neonatal. Resultados: há comprometimentos no processo de reconhecimento materno na unidade e, como desdobramento, surgem sentimentos de obrigação e insegurança para o cuidado do filho e fragilidades na autoestima. Conclusão: as interações com os profissionais de saúde e as normas e protocolos ali existentes promovem vulnerabilidades e comprometem o reconhecimento e a autonomia materna. .

RESUMEN Objetivo: analizar la experiencia derivada de la maternidad en la Unidad de Cuidados Intensivos Neonatales, centrándose en las relaciones de reconocimiento. Método: estudio cualitativo, desarrollado desde la perspectiva de la hermenéutica de Gadamer, basado en el concepto honnethiano de reconocimiento. Fueron entrevistados en profundidad diez madres de niños ingresados en una Unidad de Cuidados Intensivos Neonatales. Resultados: existen deficiencias en el proceso de reconocimiento materno en la UCIN y, por consiguiente, surgen sentimientos de inseguridad y obligación de cuidar de su hijo resultando en debilidades en su autoestima. Conclusión: las interacciones con profesionales de la salud en la unidad y las normas y protocolos allí existentes llevan a vulnerabilidades y comprometen el reconocimiento y autonomía materna. .

ABSTRACT Objective: analyze the maternal experience in a neonatal intensive care unit, focusing on relations of recognition. Method: a qualitative study, built on the perspective of Gadamer’s hermeneutics, based on Honneth’s concept of recognition. In-depth interviews were conducted with 10 mothers of children admitted to a neonatal intensive care unit. Results: failures were reported in the process of mother recognition in the unit, with consequent feelings of insecurity and obligation to child care, resulting in fragility of self-esteem. Conclusion: interactions with health professionals in the NICU and its standards and protocols cause vulnerabilities and affect maternal recognition and autonomy. .

Lung-dominant connective tissue disease among patients with interstitial lung disease: prevalence, functional stability, and common extrathoracic features / Colagenose pulmão dominante em pacientes com doença pulmonar intersticial: prevalência, estabilidade funcional e manifestações extratorácicas comuns

OBJECTIVE: To describe the characteristics of a cohort of patients with lung-dominant connective tissue disease (LD-CTD). METHODS: This was a retrospective study of patients with interstitial lung disease (ILD), positive antinuclear antibody (ANA) results (≥ 1/320), with or without specific autoantibodies, and at least one clinical feature suggestive of connective tissue disease (CTD). RESULTS: Of the 1,998 patients screened, 52 initially met the criteria for a diagnosis of LD-CTD: 37% were male; the mean age at diagnosis was 56 years; and the median follow-up period was 48 months. During follow-up, 8 patients met the criteria for a definitive diagnosis of a CTD. The remaining 44 patients comprised the LD-CTD group, in which the most prevalent extrathoracic features were arthralgia, gastroesophageal reflux disease, and Raynaud's phenomenon. The most prevalent autoantibodies in this group were ANA (89%) and anti-SSA (anti-Ro, 27%). The mean baseline and final FVC was 69.5% and 74.0% of the predicted values, respectively (p > 0.05). Nonspecific interstitial pneumonia and usual interstitial pneumonia patterns were found in 45% and 9% of HRCT scans, respectively; 36% of the scans were unclassifiable. A similar prevalence was noted in histological samples. Diffuse esophageal dilatation was identified in 52% of HRCT scans. Nailfold capillaroscopy was performed in 22 patients; 17 showed a scleroderma pattern. CONCLUSIONS: In our LD-CTD group, there was predominance of females and the patients showed mild spirometric abnormalities at diagnosis, with differing underlying ILD patterns that were mostly unclassifiable on HRCT and by histology. We found functional stability on follow-up. Esophageal dilatation on HRCT and scleroderma pattern on nailfold capillaroscopy were frequent findings and might come to serve as diagnostic criteria. .

OBJETIVO: Descrever as características de uma coorte de pacientes com colagenose pulmão dominante (CPD). MÉTODOS: Estudo retrospectivo de pacientes com doença pulmonar intersticial (DPI), anticorpo antinuclear (ANA) positivo (≥ 1/320), com ou sem autoanticorpos específicos, e com a presença de ao menos uma manifestação clínica sugestiva de doença do tecido conjuntivo (DTC). RESULTADOS: Dos 1.998 avaliados, 52 preencheram inicialmente os critérios para o diagnóstico de CPD: 37% eram homens; a média de idade ao diagnóstico era de 56 anos e a mediana do tempo de seguimento era de 48 meses. Durante o seguimento, 8 pacientes preencheram os critérios para um diagnóstico definitivo de DTC. Os 44 pacientes restantes formaram o grupo CPD, no qual as manifestações extratorácicas mais prevalentes foram artralgia, doença do refluxo gastroesofágico e fenômeno de Raynaud. Os autoanticorpos mais prevalentes nesse grupo foram ANA (89%) e anti-SSA (anti-Ro, 27%). A média de CVF no início e na última avaliação foi de 69,5% e 74,0% do predito, respectivamente (p > 0,05). Pneumonia intersticial não específica e pneumonia intersticial usual foram identificadas em 45% e 9% das TCARs, respectivamente; 36% das TCARs eram não classificáveis. Uma prevalência semelhante foi identificada na histologia. Dilatação esofágica difusa foi identificada em 52% das TCARs. Capilaroscopia subungueal foi realizada em 22 pacientes; 17 apresentavam um padrão de esclerodermia. CONCLUSÕES: No grupo CPD, houve predominância feminina, e os pacientes apresentaram alterações espirométricas leves ao diagnóstico, com diferentes padrões de DPI, em sua maioria não classificáveis, tanto em TCAR como na histologia. Estabilidade funcional foi identificada no seguimento. A dilatação esofágica em TCAR e o padrão de esclerodermia na capilaroscopia subungueal foram achados frequentes que poderiam servir como critérios diagnósticos. .

Fetal malformation in a marmoset (Callithrix jacchus): case report / Malformação fetal em sagui-de-tufo-branco (Callithrix jacchus): relato de caso

Callithrix jacchus is a neotropical primate adaptable in captivity. Colonies can be easily established in a short time and at low cost compared to other species of larger primates, which are normally used in laboratory. Because they are phylogenetically similar to humans in situations that induce anxiety, these small primates are increasingly being used in research involving the stress response. Wild animals in captivity are subjected to a series of stressful events that depending on the duration and intensity can modify the organic homeostasis. Observed in this study, serious problems occurred with the formation in fetal offspring of Callithrix jacchus kept in an environment with a high degree of stress...

O Callithrix jacchus é um primata neotropical de fácil adaptação em cativeiro. As colônias podem ser facilmente estabelecidas em um curto espaço de tempo e a um custo baixo comparado a outras espécies de primatas maiores, que são normalmente utilizados em laboratório. Por serem filogeneticamente semelhantes aos seres humanos em situações que induzem à ansiedade, esses pequenos primatas estão sendo cada vez mais utilizados em pesquisas que envolvam a resposta ao estresse. Animais silvestres em cativeiro estão submetidos a uma série de eventos estressores, os quais, dependendo da sua duração e intensidade, podem modificar a homeostase orgânica. Observaram-se, neste estudo, graves problemas ocorridos com a formação fetal nas proles de Callithrix jacchus mantidos em ambiente com alto grau de estresse...

Influência do posicionamento em prona sobre o estresse no recém-nascido prematuro avaliada pela dosagem de cortisol salivar: um estudo piloto / Influence of prone positioning on premature newborn infant stress assessed by means of salivary cortisol measurement: pilot study

Objetivo: Avaliar a influência da postura em prona sobre o estresse no recém-nascido prematuro por meio da dosagem do cortisol salivar e da avaliação das respostas fisiológicas e comportamentais, antes e após o posicionamento. Métodos: Foi realizada a coleta de saliva em cada recém-nascido em dois momentos: o primeiro (correspondente ao basal), sem manipulação prévia por 40 minutos, em decúbito lateral ou supino; e o segundo, 30 minutos após o posicionamento em prona. A frequência cardíaca e respiratória, saturação periférica de oxigênio e escala de sono de Brazelton foram registradas antes, durante e ao final do posicionamento em prona. Resultados: Participaram do estudo 16 recém-nascidos prematuros (56,3% masculino) com idade gestacional de 26 a 36 semanas, com 1 a 33 dias de vida, e peso variando de 935 a 3.050g ao nascimento e de 870 a 2.890g no dia da intervenção. Durante o posicionamento, seis recém-nascidos estavam em ar ambiente e os demais recebiam oxigênio suplementar. A mediana dos níveis de cortisol salivar foi menor durante o posicionamento em prona comparativamente ao basal (0,13 e 0,20; p=0,003), assim como a do escore de sono de Brazelton (p=0,02). A média da frequência respiratória foi menor após a intervenção (54,88±7,15 e 60±7,59; p=0,0004). As demais variáveis analisadas não apresentaram variação significativa. Conclusão: O posicionamento em prona diminuiu significativamente os níveis de cortisol salivar, da frequência respiratória e do escore de sono de Brazelton, sugerindo a correlação entre essa postura e a diminuição do estresse nesses recém-nascidos. .

Objective: This study sought to assess the influence of prone positioning on the stress of newborn premature infants through the measurement of the salivary cortisol concentration and the evaluation of physiological and behavioral responses before and after changes in body positioning. Methods: Saliva samples were collected from newborn infants at two different times: the first (corresponding to the baseline) after a period of 40 minutes during which the infants were not subjected to any manipulation and were placed in the lateral or supine position, and the second 30 minutes after placement in the prone position. Variables including heart rate, respiratory rate, peripheral oxygen saturation, and the Brazelton sleep score were recorded before, during, and at the end of the period in the prone position. Results: The sample comprised 16 newborn premature infants (56.3% male) with a gestational age between 26 and 36 weeks, postnatal age between 1 and 33 days, birth weight of 935 to 3,050g, and weight at the time of intervention of 870 to 2,890g. During the intervention, six participants breathed room air, while the remainder received oxygen therapy. The median salivary cortisol concentration was lower in the prone position compared to baseline (0.13 versus 0.20; p=0.003), as was the median Brazelton sleep score (p=0.02). The average respiratory rate was lower after the intervention (54.88±7.15 versus 60±7.59; p=0.0004). The remainder of the investigated variables did not exhibit significant variation. Conclusion: Prone positioning significantly reduced the salivary cortisol level, respiratory rate, and Brazelton sleep score, suggesting a correlation between prone positioning and reduction of stress in preterm infants. .