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The Cortisol Response of Male and Female Choroidal Endothelial Cells: Implications for Central Serous Chorioretinopathy.
Brinks, J, van Dijk, EHC, Kiełbasa, SM, Mei, H, van der Veen, I, Peters, HAB, Sips, HCM, Notenboom, RGE, Quax, PHA, Boon, CJF, et al
The Journal of clinical endocrinology and metabolism. 2022;(2):512-524
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Abstract
CONTEXT Central serous chorioretinopathy (CSC) is a severe ocular disease characterized by fluid accumulation under the retina and abnormalities in the underlying vascular layer, the choroid. CSC has a striking prevalence in males of 80% to 90% of total patients. Corticosteroids are the most pronounced extrinsic risk factor for CSC. Choroidal endothelial cells (CECs) are important for the vascular integrity of the choroid, but the effects of corticosteroid effects in these cells are unknown. OBJECTIVE We aimed to reveal the potential steroidal contribution to CSC. METHOD We characterized the expression of the glucocorticoid, mineralocorticoid, and androgen receptor in the human choroid using immunohistochemistry. Using RNA-sequencing, we describe the cortisol response in human CECs derived from 5 male and 5 female postmortem donors. RESULTS The glucocorticoid receptor was highly expressed in the human choroid, whereas no to minimal expression of the mineralocorticoid and androgen receptors was observed. The extensive transcriptional response to cortisol in human primary cultured CECs showed interindividual differences but very few sex differences. Several highly regulated genes such as ZBTB16 (log2 fold change males 7.9; females 6.2) provide strong links to choroidal vascular regulation. CONCLUSIONS The glucocorticoid receptor predominantly mediates the response to cortisol in human CECs. Interindividual differences are an important determinant regarding the cortisol response in human cultured CECs, whereas intrinsic sex differences appear less pronounced. The marked response of particular target genes in endothelial cells to cortisol, such as ZBTB16, warrants further investigation into their potential role in the pathophysiology of CSC and other vascular conditions.
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Extra-Virgin Olive Oil Improves Depression Symptoms Without Affecting Salivary Cortisol and Brain-Derived Neurotrophic Factor in Patients With Major Depression: A Double-Blind Randomized Controlled Trial.
Foshati, S, Ghanizadeh, A, Akhlaghi, M
Journal of the Academy of Nutrition and Dietetics. 2022;(2):284-297.e1
Abstract
BACKGROUND Many patients with depression are reluctant to take psychiatric medications. Hence, complementary therapies such as nutritional considerations could be advantageous. The antidepressant potential of olive oil has been proved in observational studies. OBJECTIVE The effect of extra-virgin olive oil (EVOO) on depression symptoms and cortisol and brain-derived neurotrophic factor (BDNF) levels in patients with depression was examined. DESIGN AND PARTICIPANTS This was a double-blind randomized controlled trial conducted on 73 patients suffering from major depressive disorder in Shiraz, Iran, in 2016. INTERVENTION The patients were randomly assigned to intervention (EVOO) and control (sunflower oil) groups and consumed 25 mL/d of the corresponding oil for 52 days. MAIN OUTCOME MEASURES Depression symptoms were assessed by Beck Depression Inventory-II (BDI-II) and 7-item Hamilton Depression Rating Scale (HAMD-7). Salivary cortisol levels were determined immediately after awakening and 30 minutes later. Cortisol awakening response and the area under the curve with respect to ground and increase were computed. Serum BDNF concentrations were also measured. STATISTICAL ANALYSES PERFORMED Statistical analysis was conducted based on intention-to-treat and per-protocol approaches. Within-group changes were examined with repeated measures (for BDI-II and HAMD-7) and with paired t test (for other variables). Between-group comparisons were performed with analysis of covariance after adjustment for confounding factors. RESULTS In intention-to-treat analysis, HAMD-7 score was the only variable with significant changes within and between groups, the latter as a greater decline in EVOO group (P = .001). BDI-II score did not show significant change in either group but the between-group comparison revealed a significant difference (P = .021). EVOO showed antidepressant effect in severely depressed patients (P = .017 for BDI-II and 0.008 for HAMD-7) but not in mild/moderate depression category. Serum BDNF concentrations, salivary cortisol levels at immediately after awakening (T0) and 30 minutes later, cortisol awakening response, the area under the curve with respect to ground and increase did not change within or between groups. Results of per-protocol analysis were not different. CONCLUSIONS The results of this study suggested beneficial effects of EVOO on depression symptoms in patients with severe depression but not in those with mild to moderate depression. The effects were significant from both statistical and clinical points of view.
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Plasma Cortisol and Risk of Atrial Fibrillation: A Mendelian Randomization Study.
Larsson, SC, Lee, WH, Burgess, S, Allara, E
The Journal of clinical endocrinology and metabolism. 2021;(7):e2521-e2526
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Abstract
CONTEXT Atrial fibrillation (AF), cardiac arrhythmias, and related risk factors are common in patients with Cushing's syndrome, or clinical chronic hypercortisolism. While hypercortisolism may be associated with AF, this association has not yet been ascertained causally. OBJECTIVE To determine whether plasma cortisol is causally associated with AF using a 2-sample Mendelian randomization (MR) design. METHODS Three genetic variants in the SERPINA1/SERPINA6 locus and functionally associated with plasma cortisol were identified in the CORtisol NETwork consortium (12 597 participants). Summary-level genome-wide association study (GWAS) data for the associations between the cortisol-associated variants and AF were obtained from a GWAS meta-analysis of 6 studies (60 620 AF cases and 970 216 noncases) and the FinnGen consortium (17 325 AF cases and 97 214 noncases). The fixed-effects inverse-variance weighted approach accounting for genetic correlations between variants was used for analysis. Multivariable MR analyses were conducted to assess potential mediating effects of systolic blood pressure (SBP) and waist circumference (WC). Summary-level GWAS data for SBP and WC were obtained respectively from the International Consortium of Blood Pressure (757 601 participants) and the Genetic Investigation of ANthropometric Traits consortium (232 101 participants). RESULTS One standard deviation increase in genetically predicted plasma cortisol was associated with greater risk of AF (odds ratio [OR] 1.20, 95% CI 1.06-1.35). The association attenuated when adjusting for genetically predicted SBP and WC (OR 0.99, 95% CI 0.72-1.38). CONCLUSION Evidence derived from the MR study suggests a positive association between plasma cortisol and risk of AF, likely mediated through SBP and WC.
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Effect of Vitamin C, Thiamine, and Hydrocortisone on Ventilator- and Vasopressor-Free Days in Patients With Sepsis: The VICTAS Randomized Clinical Trial.
Sevransky, JE, Rothman, RE, Hager, DN, Bernard, GR, Brown, SM, Buchman, TG, Busse, LW, Coopersmith, CM, DeWilde, C, Ely, EW, et al
JAMA. 2021;(8):742-750
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Abstract
IMPORTANCE Sepsis is a common syndrome with substantial morbidity and mortality. A combination of vitamin C, thiamine, and corticosteroids has been proposed as a potential treatment for patients with sepsis. OBJECTIVE To determine whether a combination of vitamin C, thiamine, and hydrocortisone every 6 hours increases ventilator- and vasopressor-free days compared with placebo in patients with sepsis. DESIGN, SETTING, AND PARTICIPANTS Multicenter, randomized, double-blind, adaptive-sample-size, placebo-controlled trial conducted in adult patients with sepsis-induced respiratory and/or cardiovascular dysfunction. Participants were enrolled in the emergency departments or intensive care units at 43 hospitals in the United States between August 2018 and July 2019. After enrollment of 501 participants, funding was withheld, leading to an administrative termination of the trial. All study-related follow-up was completed by January 2020. INTERVENTIONS Participants were randomized to receive intravenous vitamin C (1.5 g), thiamine (100 mg), and hydrocortisone (50 mg) every 6 hours (n = 252) or matching placebo (n = 249) for 96 hours or until discharge from the intensive care unit or death. Participants could be treated with open-label corticosteroids by the clinical team, with study hydrocortisone or matching placebo withheld if the total daily dose was greater or equal to the equivalent of 200 mg of hydrocortisone. MAIN OUTCOMES AND MEASURES The primary outcome was the number of consecutive ventilator- and vasopressor-free days in the first 30 days following the day of randomization. The key secondary outcome was 30-day mortality. RESULTS Among 501 participants randomized (median age, 62 [interquartile range {IQR}, 50-70] years; 46% female; 30% Black; median Acute Physiology and Chronic Health Evaluation II score, 27 [IQR, 20.8-33.0]; median Sequential Organ Failure Assessment score, 9 [IQR, 7-12]), all completed the trial. Open-label corticosteroids were prescribed to 33% and 32% of the intervention and control groups, respectively. Ventilator- and vasopressor-free days were a median of 25 days (IQR, 0-29 days) in the intervention group and 26 days (IQR, 0-28 days) in the placebo group, with a median difference of -1 day (95% CI, -4 to 2 days; P = .85). Thirty-day mortality was 22% in the intervention group and 24% in the placebo group. CONCLUSIONS AND RELEVANCE Among critically ill patients with sepsis, treatment with vitamin C, thiamine, and hydrocortisone, compared with placebo, did not significantly increase ventilator- and vasopressor-free days within 30 days. However, the trial was terminated early for administrative reasons and may have been underpowered to detect a clinically important difference. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT03509350.
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Psychosocial stress and cortisol stress reactivity predict breast milk composition.
Ziomkiewicz, A, Babiszewska, M, Apanasewicz, A, Piosek, M, Wychowaniec, P, Cierniak, A, Barbarska, O, Szołtysik, M, Danel, D, Wichary, S
Scientific reports. 2021;(1):11576
Abstract
We studied a sample of 146 Polish, exclusively breastfeeding mothers and their healthy born on time infants to explore the effect of perinatal psychosocial stress on breast milk composition. Maternal perinatal stress was assessed using Recent Life Changes Questionnaire summarizing stressful events from the previous six months. Stress reactivity was determined by administering the cold pressor test and measuring cortisol in saliva samples taken during the test. Breast milk sample was taken to measure energy, protein, fat, lactose, and fatty acid content. Analyses revealed that stress reactivity was positively associated with milk fat and long-chain unsaturated fatty acids and negatively associated with milk lactose. Perinatal psychosocial stress negatively affected energy density, fat as well as medium-chain and long-chain saturated fatty acids in milk. These results, together with previous studies, advocate monitoring maternal psychological status during the peripartum to promote breastfeeding and healthy infant nutrition.
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The effects of three types of exercise training on steroid hormones in physically inactive middle-aged adults: a randomized controlled trial.
Dote-Montero, M, De-la-O, A, Jurado-Fasoli, L, Ruiz, JR, Castillo, MJ, Amaro-Gahete, FJ
European journal of applied physiology. 2021;(8):2193-2206
Abstract
PURPOSE Physical inactivity and ageing are associated with imbalances in anabolic/catabolic steroid hormones, jeopardizing health. We investigated the effects of three types of training on plasma steroid hormone levels in physically inactive, middle-aged adults. METHODS A 12-week randomized controlled trial was performed with a parallel-group design. A total of 67 (36 women) middle-aged adults (45-65 years old) were randomly assigned to (1) no exercise (control), (2) concurrent training based on the international physical activity recommendations (PAR), (3) high-intensity interval training (HIIT), or (4) HIIT plus whole-body electromyostimulation (HIIT + EMS). The training volume in the PAR group was 150 min/week at 60-65% of the heart rate reserve for aerobic training and ~ 60 min/week at 40-50% of the one-repetition maximum for resistance training. The training volume in the HIIT and HIIT + EMS groups was 40-65 min/week at > 95% of the maximum oxygen uptake in long interval sessions, and > 120% of the maximum oxygen uptake in short interval sessions. RESULTS Compared to the control group, dehydroepiandrosterone sulfate increased in the PAR, HIIT, and HIIT + EMS groups (~ 14%, ~ 14%, and ~ 20%, respectively; all P < 0.01). Cortisol decreased in the PAR, HIIT, and HIIT + EMS groups (~ - 17%, ~ - 10%, and ~ - 23%, respectively; all P ≤ 0.05). Testosterone increased in the HIIT and HIIT + EMS groups (~ 28%, and ~ 16%, respectively; all P ≤ 0.01). Free testosterone increased in the HIIT and HIIT + EMS groups (~ 30% and ~ 18% respectively; all P ≤ 0.01). No significant increase in sex hormone-binding globulin was observed (P = 0.869). CONCLUSION Our findings suggest that HIIT, with or without whole-body EMS, can significantly enhance steroid hormones status in previously physically inactive middle-aged adults. The PAR program led to slight improvements than the HIIT and HIIT + EMS groups despite the application of a higher training volume. CLINICAL TRIAL REGISTRY NCT03334357 (ClinicalTrials.gov). November 7, 2017 retrospectively registered.
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A 2 Week Cross-over Intervention with a Low Carbohydrate, High Fat Diet Compared to a High Carbohydrate Diet Attenuates Exercise-Induced Cortisol Response, but Not the Reduction of Exercise Capacity, in Recreational Athletes.
Terink, R, Witkamp, RF, Hopman, MTE, Siebelink, E, Savelkoul, HFJ, Mensink, M
Nutrients. 2021;(1)
Abstract
Low carbohydrate, high fat (LCHF) diets are followed by athletes, but questions remain regarding effects of LCHF on metabolic adaptation, exercise-induced stress, immune function and their time-course. In this cross-over study, 14 recreational male athletes (32.9 ± 8.2 years, VO2max 57.3 ± 5.8 mL/kg/min) followed a two week LCHF diet (<10 En% carbohydrates (CHO), ~75En% Fat) and a two week HC diet (>50 En% CHO), in random order, with a wash-out period of >2 weeks in between. After 2 days and 2 weeks on either diet, participants performed cycle ergometry for 90 min at 60%Wmax. Blood samples for analysis of cortisol, free fatty acids (FFA), glucose and ketones, and saliva samples for immunoglobin A (s-IgA) were collected at different time points before and after exercise. The LCHF diet resulted in higher FFA, higher ketones and lower glucose levels compared to the HC diet (p < 0.05). Exercise-induced cortisol response was higher after 2 days on the LCHF diet (822 ± 215 nmol/L) compared to 2 weeks on the LCHF diet (669 ± 243 nmol/L, p = 0.004) and compared to both test days following the HC diet (609 ± 208 and 555 ± 173 nmol/L, both p < 0.001). Workload was lower, and perceived exertion higher, on the LCHF diet compared to the HC diet on both occasions. A drop in s-IgA following exercise was not seen after 2 days on the LCHF diet, in contrast to the HC diet. In conclusion, the LCHF diet resulted in reduced workload with metabolic effects and a pronounced exercise-induced cortisol response after 2 days. Although indications of adaptation were seen after 2 weeks on the LCHF diet, work output was still lower.
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Hair Cortisol Concentration, Weight Loss Maintenance and Body Weight Variability: A Prospective Study Based on Data From the European NoHoW Trial.
Larsen, SC, Turicchi, J, Christensen, GL, Larsen, CS, Jørgensen, NR, Mikkelsen, MK, Horgan, G, O'Driscoll, R, Michalowska, J, Duarte, C, et al
Frontiers in endocrinology. 2021;:655197
Abstract
UNLABELLED Several cross-sectional studies have shown hair cortisol concentration to be associated with adiposity, but the relationship between hair cortisol concentration and longitudinal changes in measures of adiposity are largely unknown. We included 786 adults from the NoHoW trial, who had achieved a successful weight loss of ≥5% and had a body mass index of ≥25 kg/m2 prior to losing weight. Hair cortisol concentration (pg/mg hair) was measured at baseline and after 12 months. Body weight and body fat percentage were measured at baseline, 6-month, 12-month and 18-month visits. Participants weighed themselves at home ≥2 weekly using a Wi-Fi scale for the 18-month study duration, from which body weight variability was estimated using linear and non-linear approaches. Regression models were conducted to examine log hair cortisol concentration and change in log hair cortisol concentration as predictors of changes in body weight, change in body fat percentage and body weight variability. After adjustment for lifestyle and demographic factors, no associations between baseline log hair cortisol concentration and outcome measures were observed. Similar results were seen when analysing the association between 12-month concurrent development in log hair cortisol concentration and outcomes. However, an initial 12-month increase in log hair cortisol concentration was associated with a higher subsequent body weight variability between month 12 and 18, based on deviations from a nonlinear trend (β: 0.02% per unit increase in log hair cortisol concentration [95% CI: 0.00, 0.04]; P=0.016). Our data suggest that an association between hair cortisol concentration and subsequent change in body weight or body fat percentage is absent or marginal, but that an increase in hair cortisol concentration during a 12-month weight loss maintenance effort may predict a slightly higher subsequent 6-months body weight variability. CLINICAL TRIAL REGISTRATION ISRCTN registry, identifier ISRCTN88405328.
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Oxytetracycline-hydrocortisone ointment reduces the occurrence of both dry socket and post-extraction pain after third molar extraction: An observational study.
Otake, H, Sato, Y, Nakatani, E, Hawke, P, Takei, S, Ogino, A, Asai, H, Abe, A, Fukuta, K, Adachi, M
PloS one. 2021;(7):e0254221
Abstract
OBJECTIVES Dry socket and post-extraction pain are typical discomforts experienced by patients after tooth extraction. In this study, we inserted gauze coated with oxytetracycline-hydrocortisone ointment into the extraction socket immediately after lower third molar extraction and then evaluated the occurrence of dry socket and post-extraction pain compared with gauze non-insertion. METHODS This retrospective study was carried out on patients undergoing lower third molar extraction in the Department of Oral Surgery at Shizuoka Prefectural General Hospital in Shizuoka, Japan from November 2018 to October 2019. A comparison was carried out between a gauze-insertion group and a non-insertion group. The occurrence versus non-occurrence of dry socket was determined, and degree of pain was assessed based on a visual analogue scale (VAS) and on patients reporting the number of loxoprofen sodium oral analgesic tablets (60mg/tablet) that they had taken. Dry socket was defined as patient-reported spontaneous pain that did not subside 1 to 3 days postoperatively. Spontaneous post-extraction pain was recorded four times: on the operative day, on the first postoperative day (POD1), on POD3, and during suture removal (POD7). RESULTS The occurrence of dry socket was lower in the gauze-insertion group than in the non-insertion group (0.9%, 2/215 vs. 19.6%, 9/46, p<0.001). The results also showed that both VAS-defined pain level and the number of analgesic tablets taken were lower in the gauze-insertion group than in the non-insertion group on POD3 and POD7. CONCLUSIONS AND CLINICAL RELEVANCE Inserting gauze coated with oxytetracycline-hydrocortisone ointment into the extraction socket immediately after third molar extraction reduces the occurrence of both dry socket and post-extraction pain.
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The effect of dairy products and non-dairy snacks on food intake, subjective appetite and cortisol levels in children: a randomized control study.
Gheller, BJF, Li, AC, Gheller, ME, Armstrong, T, Vandenboer, E, Bellissimo, N, Anini, Y, Hamilton, J, Nunes, F, Mollard, RC, et al
Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme. 2021;(9):1097-1104
Abstract
Dairy snacks are available in various physical forms and their consumption is linked to improved metabolic health. The objective of this study was to determine the effect of dairy snacks of different physical forms on short-term food intake (FI), subjective appetite, and the stress hormone, cortisol, in children. Following a repeated-measures crossover design, 40 children aged 9-14 years randomly consumed 1 of 5 isoenergetic (180 kcal) snacks per study session. These snacks included solid (potato chips, cookies, and cheese), semi-solid (Greek yogurt), and fluid (2% fat milk) snacks. FI was measured 120 min after snack consumption. Subjective appetite was measured at 0 (immediately before the snack), 15, 30, 45, 60, 90, and 120 min. Salivary cortisol (n = 18) was measured after the Greek yogurt and cookie snacks at 0, 30, 60, 90, and 120 min. FI did not differ between snacks (P = 0.15). The Greek yogurt (P < 0.0001) and cheese (P = 0.0009) snacks reduced average appetite compared with the 2% fat milk snack. Salivary cortisol levels were not affected by snack (P = 0.84). This study demonstrates that dairy snacks are as effective as other popular snacks at influencing subsequent FI. However, solid and semi-solid dairy snacks are more effective at repressing subjective appetite than a fluid dairy snack. Registered at ClinicalTrials.gov (NCT02484625). Novelty: Milk, Greek yogurt and cheese have a similar effect on short-term food intake in children as popular potato chips and cookie snacks. Solid, semi-solid and liquid snacks have a similar effect on short-term food intake in children.