Cortisol awake response imbalance as an indicator of acute central serous chorioretinopathy: Relationship with choriocapillaris and choroidal features.

Purpose: The purpose of the present study was to measure in central serous chorioretinopathy (CSC) the salivary cortisol awake response (CAR) delta percentage (Δ%) variation, a distinct and robust indicator of cortisol rhythm during wakefulness, commonly proposed as a marker of hypothalamic-pituitary adrenal (HPA) axis activity, whose alteration is frequently associated with several adverse health outcomes. Methods: In the present cross-sectional observational study, salivary CAR Δ% variation was assessed in 17 adult male subjects affected by acute naïve CSC and compared to 17 matched healthy controls. Choroid vasculature metrics were assessed in the study population by measuring the subfoveal choroidal thickness (FCT) and the choroidal vascularity index (CVI) by the imaging technique of enhanced-depth imaging spectral-domain optical coherence tomography (EDI-SD-OCT). Furthermore, flow signal void area features of the choriocapillaris were evaluated in the study population using OCT angiography (OCTA). Results: Both the control and CSC groups showed a physiological cortisol increase that occurred during the first 30 min after awaking. However, CSC adult male patients showed remarkably blunted CAR Δ% variation in comparison with controls, which might reflect a CSC-related imbalance of HPA axis activity. Statistically significant correlations were shown by Pearson's correlation test between salivary CAR Δ% and the selected choroidal and choriocapillaris imaging biomarkers (FCT, CVI, and flow signal void area) in the study population. Conclusion: In conclusion, alterations of the CAR Δ% increase, associated with choroidal-retinal metrics, might provide a window into the physiopathology of acute CSC, suggesting a possible common factor to explain the association between stress and CSC.

Biopsychosocial Illness Model: From the Lung to the Eye.

Studies on the impact of different pathologies on the quality of life have made the translation of multidisciplinary scientific knowledge into a unified model of biopsychosocial disease possible in which several important biological variables are integrated with psychological-functional and sociological variables [...].

Relationship of Choroidal Vasculature and Choriocapillaris Flow With Alterations of Salivary α-Amylase Patterns in Central Serous Chorioretinopathy.

Purpose: An abnormality in choroidal vasculature is a known factor in the pathogenesis of central serous chorioretinopathy (CSC), a chorioretinal disease affecting mostly middle-aged males. The purpose of the present study was to investigate the role of the autonomic nervous system (ANS) in the pathophysiology of CSC. Methods: This was a cross-sectional observational study in which characteristic choroidal vasculature metrics were assessed by measuring the subfoveal choroidal thickness (FCT) and the choroidal vascularity index (CVI) using the imaging technique of enhanced-depth imaging spectral-domain optical coherence tomography (EDI-SD-OCT). Furthermore, flow signal void area features were also evaluated in the study population using OCT angiography (OCTA). Diurnal patterns of salivary α-amylase (a-AMY) production, proposed as a marker of autonomic activity, were assessed in an adult male study population affected by acute naïve CSC in comparison with matched healthy controls. Results: Results include an overall higher diurnal output of salivary a-AMY production, which is in line with the phenomenon of a sympathetic "drive" playing a role in the pathophysiology of CSC, and a flattened diurnal percentage variation in α-AMY in CSC-affected subjects. Furthermore, Pearson's coefficient test revealed statistically significant correlations between salivary α-AMY diurnal percentage variation and selected choroidal imaging biomarkers (FCT, CVI, and flow signal void area). Finally, multiple linear regression analysis identified salivary α-AMY diurnal percentage production as the sole predictor of the CVI and flow signal void area in the study population. Conclusions: Autonomic nervous system dysregulation was highlighted in CSC patients.

Exploring the Biopsychosocial Pathways Shared by Obstructive Sleep Apnea (OSA) and Central Serous Chorioretinopathy (CSC): A Literature Overview.

This study addressed the following question: "Is it possible to highlight the link between obstructive sleep apnea (OSA) and central serous chorioretinopathy (CSC) through common biopsychosocial pathogenetic pathways?". The study was conducted through electronic searches of the PubMed, Web of Science, and Scopus databases. All relevant selected human research studies published from January 2003 to December 2020 were included. The scientific literature search was performed through repeated use of the words "OSA" and/or "acute/chronic CSC" paired with "biomedical/biopsychosocial illness model", "psychopathology", "stress", "personality characteristics", "functional diseases", "comorbidity", and "quality of life" in different combinations. Our literature search identified 213 reports, of which 54 articles were ultimately reviewed in this paper. Taken together, the results indicate that there is a cross-link between OSA and CSC that can be classified among biopsychological disorders in which various major biological variables integrate with psychological-functional and sociological variables; many of these variables appear in both diseases. This concept can have important implications for improving patients' quality of life, thus providing the necessary strategies to cope with challenging life events even through nonpharmacological approaches.

Psychological Profile and Distinct Salivary Cortisol Awake Response (CAR) in Two Different Study Populations with Obstructive Sleep Apnea (OSA) and Central Serous Chorioretinopathy (CSC).

Obstructive sleep apnea (OSA) and central serous chorioretinopathy (CSC) are in terms of nosography different pathologies, however they share a stress-related physio-pathogenetic component, not yet explored in depth. Therefore, the aim of the present study was to ascertain whether OSA and CSC share a common profile, specifically in cortisol production focusing on the cortisol awake response (CAR), the area under curve (AUCCAR) and the SLOPECAR compared with healthy matched controls. Furthermore, standardized self-administered questionnaires were used to identify mental health status related to depression, anxiety and subjective stress perception levels in the study populations. The results showed hypothalamus-pituitary-adrenal (HPA) axis activity anomalies, represented by a flattening CAR in the OSA group and a statistically significant increase in cortisol production in CSC patients at awakening. This disarrangement of the HPA axis activity associated with elevated distress and mental health scores, and its presence in both patients with OSA and patients with CSC, might represent the shared path explaining the stress-related component in these diseases. Further research is needed to investigate the psycho-neuro-endocrinological aspects of OSA and CSC to determine whether psychoeducation on effective stress coping strategies might be of value in improving the quality of life of OSA and CSC patients.

Diurnal trajectories of salivary cortisol and α-amylase and psychological profiles in patients with central serous chorioretinopathy.

It has been hypothesized that the occurrence of central serous chorioretinopathy (CSC) might be associated with stress. Therefore, our purpose was to investigate the diurnal trajectories of salivary cortisol and α-amylase (α-Amy) - markers of hypothalamic-pituitary-adrenal (HPA) axis and sympathetic-adrenal-medullary (SAM) system activity, respectively - and psychological profiles in idiopathic acute CSC. This cross-sectional observational case-control study, which included self-reported psychometric questionnaires, was formally approved by the Ethics Committee. Written informed consent was obtained from all participants. Home diurnal saliva collection was scheduled at several timepoints: at awakening, 30 and 60 min later, and at approximately 13:00 h and 20:00 h. Twenty consecutive male subjects with first-episode CSC attending the outpatient clinic of the Retina Medical Service at the Bietti Foundation were enrolled in the study. Twenty age-matched subjects were recruited as controls. After their initial enrollment, 3 subjects per group were excluded. The production of cortisol and α-Amy and the scores on the negative subscale of the Positive/Negative Affect Schedule, the Daily Hassles and Stress Scale and the Beck Depression Inventory were higher in the CSC group than in the control group. To estimate the diurnal trends in the production of salivary cortisol and α-Amy, an equation was derived for each group of the study population. The equations describing the interpolated regression lines gave salivary cortisol and salivary α-Amy slopes that were determined to be significantly different by Student's t-test (cortisol: t = 3.533, p < .001; α-Amy: t = 2.382, p = .018). Furthermore, the area under the curve with respect to the ground (AUCG) was calculated to summarize repeated salivary biomarker measurements from 07:00 h to 08:00 h for assessment of the cortisol awakening response (CAR) and the α-Amy awakening response (AR). The diurnal cortisol AUCG and diurnal α-Amy AUCG were calculated from 07:00 h to 20:00 h. The CAR AUCG values of the CSC patients were significantly higher than those of the controls. No differences between the two groups were detected for the α-Amy AR AUCG. The present study adds novel information to the growing body of data suggesting that abnormal diurnal activity of the HPA axis and the SAM system is associated with CSC in susceptible individuals, providing ophthalmologists with a new chronobiological approach for these patients.

[Effects of Group Psychoeducation on stress reactivity neuroendocrine profile in stabilized bipolar patients. A controlled study]. / Effetti della psicoeducazione di gruppo sul profilo neuroendocrino di reattività allo stress in pazienti bipolari stabilizzati. Uno studio controllato.

INTRODUCTION: Patients with bipolar disorder show a high relapse rate generally related to their poor adherence to the prescribed medications and to their high stress vulnerability, linked to genetic, neuroendocrine and cognitive factors. AIMS: The first aim of this study was to verify if for a group of pharmacologically stabilized bipolar patients, the attendance to a Group Psychoeducation program according to the Barcelona model would result in an improvement of their stress resilience, as measurable by evaluating their morning cortisol secretory profile. The second aim of the study has been to verify if these effects would maintain stable over time, organizing follow-up evaluations, after one year and after two years form the end of the group psychoeducation program. MATERIALS AND METHODS: 96 patients who had been euthymic for at least 6 months and were under stabilized pharmacologic maintenance treatment, were randomized in two groups: pharmacological treatment as usual (TAU) or pharmacological treatment plus group Psychoeducation (PE). Patients in both groups underwent a psychological assessment (HAMD, YMRS e ARMS), and to a functional assessment of the HPA axis activity, obtained evaluating cortisol levels from salivary samples collected in 5 different moments of the day: at baseline, at the end of the group psychoeducation program, and after 1 year and 2 years from the end of the last PE session. RESULTS: At the end of the study, both groups (PE and TAU) did not show any significant intergroup difference with regard to all the clinical variables and the patients' adherence to the prescribed medications. On the contrary, significative intergroup differences were observed with regard to morning cortisol secretory profile, that was found normalized at the endpoint only among patients of the PE group, but not among those of the TAU group. This normalization of the morning cortisol secretory profile observed among patients of the PE group, proved to maintain stably overtime, since it was observed also in the two follow-up assessments, organized after 1 year and after 2 year from the end the treatment. DISCUSSION: Data collected in this study may indicate that the efficacy of the psychoeducation programs for bipolar patients may activate an improvement of the functional activation of the HPA axis, and so obtaining a reduction of their stress vulnerability.

Investigating the Hypothesis of Stress System Dysregulation as a Risk Factor for Central Serous Chorioretinopathy: A Literature Mini-Review.

Background: This mini-review addressed the question "what do we know about the association between the dysregulation of stress systems (HPA axis and SAM) and the onset and prognosis of CSC in adult populations?" Methods: The literature mini-review was conducted through electronic searches using the PubMed, Web of Science, and Scopus databases. All published human and animal studies with both observational and experimental designs from 1966 to October 2018 were included. Results: Our search identified 229 reports, of which 32 articles were ultimately identified to be reviewed in this paper. Among these key articles, twenty-three were related to exogenous and/or endogenous high glucocorticoids as risk factors for CSC, seven were related to Type-A behavior and chronic psychological distress as risk factors for idiopathic CSC, and two were related to stress-induced animal models of CSC. Nineteen out of twenty-three studies in the first group reported a consistent association between high circulating corticosteroids and the onset and prognosis of CSC. Six out of seven studies in the second group reported a consistent association between stress-induced allostatic (over)load and the appearance of more- or less-severe CSC disorders, assuming that elevated circulating steroids may constitute a kind of risk factor for the eye through dysregulation of the HPA axis. All the selected studies reported HPA axis dysregulation as a possible common factor to explain the association between high circulating corticosteroids and CSC. In contrast, the involvement of the SAM system is only indirectly taken into consideration through the PA and HR measures and/or plasma and 24-h urinary catecholamine levels. Therefore, information regarding the involvement of SAM system dysregulation in the onset and prognosis of CSC is lacking. This observation is particularly relevant in view of the fact that animal models of CSC in monkeys are primarily induced by adrenergic hypertonia and that the course of experimental CSC is not further exacerbated by the administration of corticosteroids.

Distinct activation of the sympathetic adreno-medullar system and hypothalamus pituitary adrenal axis following the caloric vestibular test in healthy subjects.

INTRODUCTION: The vestibular acute stress induces reversible alert-like reactions that involve the sympathetic adrenal-medullar system and hypothalamic-pituitary-adrenal axis responses. The present study aimed to evaluate salivary α-amylase and salivary cortisol production in relation with cardiovascular reactivity induced by acute stress in healthy subjects. MATERIAL AND METHODS: Forty-eight young healthy male volunteers were examined under basal conditions and at various times after reaching the maximal nystagmic reaction following air caloric vestibular test. Heart rate, systolic blood pressure, diastolic blood pressure and mean arterial pressure were recorded at the same time as measurement of the salivary α-amylase and salivary cortisol. At the end of the caloric vestibular test session, perceived stress scale questionnaires were administered to measure the self-perceived stress impact induced by the task, and individual scores were compared with those measured on the enrollment day. RESULTS: Following caloric vestibular test-evoked vertigo, salivary α-amylase and cortisol showed distinct trends in their production after acute stress: Student's t-test was used to compare the α-amylase vs cortisol slopes of the respective interpolated regression lines, and the difference was significant (t = -3.283; p<0.001); an increase in salivary cortisol production corresponded with a decrease in the salivary α-amylase concentration. In addition, salivary biomarker modifications were associated with consistent changes in the heart rate, systolic blood pressure and mean arterial pressure. CONCLUSIONS: Using the air caloric vestibular test task as a stressor, the present study demonstrated a connection between the acute hormonal stress response to vestibular stimulation and cardiovascular output. However, further research is needed before we can define the potential importance of the consistent cardiovascular activity changes evoked by vestibular stimulation and the possible functional consequences for cardiovascular regulation and orthostatic tolerance in humans.

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.

No definitive evidence for a connection between autoimmune thyroid diseases and stress in women.

The purpose of this literature review was to examine the available clinical studies performed during the last 15 years to identify if there is a causal relationship between the onset and course of autoimmune thyroid diseases (AITDs) and the hypothalamic-pituitary-adrenal (HPA) axis/sympathetic-adrenomedullary system (SAM) (dys)function in women. Using the PubMed, Web of Science and Scopus databases, a comprehensive search was performed, and 14 articles were finally identified. The majority of selected studies suggested a causal connection between Graves' Disease (GD) and stress, as well as between Hashimoto Thyroiditis (HT), with its variant postpartum thyroiditis, and stress. However, due to heterogeneity in the protocols, mainly based on the theoretical side effects of stress on the immune-neuroendocrine system, and the different modalities used to establish the impact of stress on individuals, no definitive conclusions could be reached to explain the mechanisms by which stress contributes to the onset of AITDs in women and to determine whether stress management could help in modifying the course of AITDs.

Imbalance in the diurnal salivary testosterone/cortisol ratio in men with severe obstructive sleep apnea: an observational study.

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.

Salivary biomarkers of obstructive sleep apnea syndrome in children.

OBJECTIVES: The present pilot study was performed to evaluate the HPA axis and ANS activity by measuring salivary cortisol and α-amylase diurnal trajectory and production, respectively, in mild or moderate-to-severe (MS) OSA-affected, but otherwise healthy, children. Moreover, a correlative analysis was performed between the salivary biomarker concentrations and the PSG variables characterizing the OSA severity. METHODS: We studied 27 consecutive OSA patients (13 mild OSA; 14 MS OSA) and seven healthy children who were enrolled as controls by collecting salivary samples and measuring cortisol and α-amylase levels using enzyme-linked bioassays. RESULTS: Compared with controls, both mild and MS OSA children showed: (1) increased salivary cortisol diurnal production, (2) maintenance of the physiological circadian activity of the HPA axis, and (3) no changes in α-amylase diurnal trajectory and production. In addition, morning salivary cortisol concentrations was negatively associated with the disease severity in the MS OSA group. CONCLUSIONS: OSA is associated with dysregulation of the HPA axis activity in children, the latter potentially underlying some of the adverse consequences of the disease.

Restoring the salivary cortisol awakening response through nasal continuous positive airway pressure therapy in obstructive sleep apnea.

Partial and largely conflicting data are currently available on the interplay between obstructive sleep apnea (OSA) and hypothalamus-pituitary-adrenal axis (HPA) activity in adult obese men. This study was performed to evaluate the daily trajectories of salivary cortisol, specifically with respect to the salivary cortisol awakening response (CAR), a common method used to assess HPA axis activity. The main findings of this study were that adult male obese subjects who were newly diagnosed with severe OSA showed the following: (1) a flattening of the CAR; (2) levels of cortisol at awakening that were lower than those of the controls; and (3) maintenance of the physiological circadian activity of the HPA axis, with the highest hormone concentrations produced in the morning and the lowest in the evening. This study was also designed to investigate the effects of 3 and 6 mos of treatment with continuous airways positive pressure (CPAP). CPAP use resulted in a significant recovery of the sleep patterns disrupted by OSA; moreover, mild neuropsychological signs of depression and anxiety in severe OSA patients were concomitantly progressively improved by CPAP treatment. Furthermore, this study reports that 3 and 6 mos of CPAP therapy restored the presence of CAR and was able to significantly reduce the difference in the morning cortisol levels between the OSA and control groups. In conclusion, we report here that compared with obese nonapneic matched controls, OSA patients present a dysregulation of HPA axis activity, as shown by the flattening of the diurnal pattern of cortisol production in response to repeated challenge due to hypoxia and sleep fragmentation. This dysregulation was especially detectable in the first hour after awakening and restored after 3 and 6 mos of treatment with CPAP.

Dysregulation of diurnal salivary cortisol production is associated with spontaneous preterm delivery: a pilot study.

OBJECTIVES: The purpose of this study was to evaluate whether the diurnal fluctuation of salivary cortisol and its overall diurnal secretion are associated with the length of gestation in patients who were admitted to the hospital with an assigned diagnosis of possible preterm labor (PL) at a gestational age of 28-33 weeks. METHODS: In 22 patients, maternal saliva samples were collected for a cortisol assay 4 times per day (8 AM, 12 AM, 4 PM and 8 PM) on day 4 and day 6 after antenatal corticosteroid prophylaxis to prevent neonatal respiratory distress syndrome. RESULTS: Eight patients who ultimately delivered before term (32.6 ± 1.7 gestation weeks) showed an inverted fluctuation of salivary cortisol on both days 4 and 6, morning cortisol levels being significantly lower than evening levels. In contrast, in 14 patients who delivered at term (39.5 ± 0.6 gestation weeks), the physiological diurnal fluctuation of salivary cortisol was maintained. In addition, a distinctive feature of women delivering before term was a significantly hampered salivary cortisol diurnal production measured on day 6. CONCLUSIONS: Corticoadrenal activity is dysregulated and anticipates very preterm delivery in women with an assigned diagnosis of possible PL.

Menopausal symptoms after the discontinuation of long-term hormone replacement therapy in women under 60: a 3-year follow-up.

BACKGROUND: Prescriptions for hormone replacement therapy (HRT) declined following the publication of the Women's Health Initiative study. The number of women who experience recurrence of menopausal symptoms after discontinuation of long-term HRT (LT-HRT), the length of time these symptoms last and the preferred alternative treatments remain unknown. METHODS: This prospective 3-year follow-up study analyses the prevalence and intensity of menopausal symptoms that occur in young postmenopausal women who discontinued LT-HRT. Symptoms were evaluated using the Menopause Rating Scale. RESULTS: Women (254) who discontinued LT-HRT (mean use: 6.9 ± 2.3 years) were recruited. Mean age at menopause was 48.1 ± 3.4 years. Mean age at discontinuation was 56.8 ± 3.7 years. 23% of the women were lost to follow-up. Of the remaining 196 women, 93% experienced a recurrence of menopausal symptoms within the first year, 25% resumed low-dose HRT, 62% used vaginal estrogens, 54% used phytoestrogens, and 2% used alternative therapies. A decrease in symptom prevalence and intensity was observed during the 3-year follow-up. CONCLUSIONS: Symptoms re-appeared in a significant proportion of patients within the first year after discontinuation of LT-HRT. However, after 3 years, the majority of these women were asymptomatic. Patients who discontinue LT-HRT may require a more detailed follow-up immediately after the discontinuation of treatment.

Acute hypobaric-hypoxia challenge and salivary cortisol and DHEA-S in healthy male subjects.

BACKGROUND: Hypobaric hypoxia is a stressful emergency situation that can cause a degradation of the sensory, motor, and higher cognitive functions necessary for safe flight. METHODS: We studied the salivary cortisol and dehydroepiandrosterone-sulfate (DHEA-S) concentrations of 12 healthy male military aviators (AV) exposed to an altitude-induced hypoxia challenge in a hypobaric chamber. A matched control group (C) of eight flight physiology instructors wearing oxygen masks during the challenge was studied. Salivary samples were collected every 2 h on 3 experimental days (the day before, the day of, and the day after the hypobaric chamber challenge). RESULTS: In the AV group, salivary cortisol concentrations showed a statistically significant increase from 5.42 +/- 0.15 measured at 08:30 to 11.37 +/- 1.86 ng ml(-1) during the hypobaric chamber challenge and a statistically significant increase in DHEA-S was also measured (from 3.15 +/- 0.42 ng x ml(-1) at 08:30 to 5.99 +/- 0.15 ng x ml(-1)). The day after the challenge, the concentrations of both hormones were comparable to those measured the day before; neither C nor AV showed any disturbances of the physiological diurnal fluctuations of cortisol and DHEA-S. No differences were found among the cortisol/DHEA-S ratios measured during the 3 experimental days in the AV group. DISCUSSION: In spite of having experienced a psycho-physical stress, the AVs did not show any dysregulation of the diurnal fluctuations of cortisol and DHEA-S, thus presenting a good level of stress resilience. Data presented in this paper are consistent with recent literature suggesting a stress-buffering role of DHEA-S.

In vitro and in vivo study of cucurbitacins-type triterpene glucoside from Citrullus colocynthis growing in Saudi Arabia against hepatocellular carcinoma.

Chromatographic investigation of fruits obtained from Citrullus colocynthis, growing in Saudi Arabia, led to isolation of two compounds; Cucurbitacin E glucoside (Cu E, 1), and Cucurbitacin I glucoside (Cu I, 2). The chemical structures of 1 and 2, were elucidated by spectroscopic analyses include; 1D ((1)H and (13)C) and 2D (COSY, HMQC and HMBC) NMR and ESI-MS spectroscopy. The in vitro cytotoxic activity against hepatoma cell line (HepG2) and mice-bearing tumor of Ehrlich's ascites carcinoma (EAC) of the compounds were estimated. Both compounds had potent inhibitory activity on HepG2 with IC(50) 3.5 and 2.8 nmol/mL, respectively. In addition to these activities, the in vivo study employing EAC, showed the capability of both compounds to prolong the survival time, life span and normalize the biochemical parameters of the infected mice with EAC.

Awakening responses and diurnal fluctuations of salivary cortisol, DHEA-S and α-amylase in healthy male subjects.

OBJECTIVES: Because the cortisol awakening response (CAR) has received increasing attention as a useful index of adrenocortical activity, the primary objective of this study was to investigate the presence of an awakening response for various salivary biomarkers of adrenocortical activity, including dehydroepiandrosterone-sulphate (DHEA-S), which acts as a cortisol antagonist, and α-amylase, which is a predictor of circulating catecholamine activity. Salivary biological indicators are considered to be valuable markers of hypothalamus-pituitary-adrenal (HPA) axis diurnal activity. METHODS: In an attempt to overcome problems associated with non-adherence to the requested sampling protocol, only young, healthy males with a physiological CAR value (defined as a 50% increase in salivary cortisol within 30 min after waking) were included in the study (67 out of 102 who initially enrolled met this criterion). RESULTS: Our results suggested that, as is already known for cortisol, DHEA-S and α-amylase have significant awakening responses. In addition, daily profile of salivary cortisol, α-amylase and DHEA-S fluctuations were analysed. Significant correlations were found between salivary cortisol, DHEA-S and α-amylase levels. The results showed that cortisol and DHEA-S concentrations were inversely correlated with α-amylase levels. CONCLUSION: This correlation confirmed the distinctiveness of the two regulatory systems: salivary cortisol and DHEA-S concentrations reflect the activity of the HPA axis, whereas α-amylase activity is more closely related to sympathetic activity. In addition, the present study emphasizes the potential value of saliva collection (which is both easy and stress-free) in monitoring changes of adrenal function, confirming that multiple sampling (especially within 1 h after awakening) is necessary to reliably characterise biomarker activity when investigating neuroendocrine changes under various conditions.