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A single administration of 'microbial' D-alanine to healthy volunteers augments reaction to negative emotions: A comparison with D-serine.
Capitão, LP, Forsyth, J, Thomaidou, MA, Condon, MD, Harmer, CJ, Burnet, PW
Journal of psychopharmacology (Oxford, England). 2020;(5):557-566
Abstract
BACKGROUND Activation of the glutamate N-methyl-D-aspartate receptor with its co-agonist D-serine has been shown to improve subjective mood in healthy volunteers. D-alanine is another potent N-methyl-D-aspartate receptor co-agonist which arises from the natural breakdown of host gut microbes, and is predominantly sequestered in the pituitary. This may suggest that D-alanine influences the neuroendocrine stress response which may then impact on emotion. AIMS The current study explored the effects of D-serine and D-alanine on emotional processing, cognition and the levels of the stress hormone cortisol in healthy volunteers. METHODS In a double-blind, placebo-controlled randomised study, participants (n=63) received a single oral dose of either D-serine, D-alanine (60 mg/kg) or placebo and then performed the Emotional Test Battery and N-back task (two hours post-administration) and provided saliva samples at fixed intervals. RESULTS Subjects administered with D-alanine were faster at identifying facial expressions of fear, surprise and anger, and at categorising negative self-referential words. Participants on D-alanine also showed a trend to recall more words than placebo in a memory task. D-serine did not have any meaningful effects in any of the tasks. Neither amino acid had a significant effect on salivary cortisol or working memory. CONCLUSION This study is the first to suggest that D-alanine can modulate emotional cognitive processing after a single dose. The lack of findings for D-serine nevertheless contrasts a previous study, emphasising a need for further investigation to clarify discrepancies. A better understanding of the physiological actions of D-amino acids would be beneficial in evaluating their therapeutic potential.
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Long-term prednisone versus hydrocortisone treatment in children with classic Congenital Adrenal Hyperplasia (CAH) and a brief review of the literature.
Ahmed, SEAM, Soliman, AT, Ramadan, MA, Elawwa, A, Abugabal, AMS, Emam, MHA, De Sanctis, V
Acta bio-medica : Atenei Parmensis. 2019;(3):360-369
Abstract
BACKGROUND Debate still exist about the safety of long-term use of prednisone (PD) versus hydrocortisone (HC) for treating children with congenital adrenal hyperplasia -21OH D (CAH). Despite recent developments in congenital adrenal hyperplasia -21OH D (CAH), several issues related to patient growth and final height remain unsolved. Debate still exist about the safety of long-term use of PD versus HC for treating children with CAH. The mechanism by which glucocorticoid therapy interferes with growth is complex and multifactorial. Relatively slight supra-physiologic levels may be enough to blunt growth velocity. An increased risk of developing obesity is another possible consequence of hyper-cortisolism in children with CAH. OBJECTIVES OF THE STUDY To evaluate the anthropometric and biochemical effects of long-term PD versus HC treatment in children with CAH-21OHD. A brief review of the literature is also reported. PATIENTS AND METHODS This retrospective study evaluated linear growth and biochemical data of thirty children with classic CAH (19 females and 11 males), who were on PD (n=22) or HC (n=8) treatment, since their first diagnosis. Clinical data included age, gender, duration of therapy, dose of HC and or equivalent dose of HC in the PD group, blood pressure, height (Ht) and weight. Ht-SDS and BMI were also calculated. Biochemical data included measurement of 17- OH progesterone, cholesterol, triglycerides (TG), HDL, LDL, fasting glucose, and insulin concentrations. HOMA-IR was calculated. Carotid intima-media thickness (CIMT) was measured using high-resolution B-mode ultrasonography. Thirty normal age matched children were used as controls for the anthropometric and CIMT data. RESULTS The age of children and duration of treatment did not differ among the two treatment groups. After a mean of 6 years of treatment, the Ht-SDS and BMI did not differ between the three groups of children. The equivalent hydrocortisone dose of children on prednisone was significantly higher than the dose for the hydrocortisone group. Both systolic and diastolic blood pressures (BP) of children on PD was slightly higher compared to those on hydrocortisone group. However, the BP of the 2 treatment groups was not different compared to control children. Fasting blood glucose, homeostatic model assessment insulin resistance (HOMA-IR), plasma TG, HDL, and cholesterol did not differ among the two treatment groups. LDL levels were significantly higher in the PD group versus the HC group. The mean CIMT did not differ among the two treatment groups but was significantly higher in the treated groups versus controls. There was a significant linear correlation between BMI-SDS and CIMT (r=0.37, p=0.047). CONCLUSIONS Children with CAH-21OHD who were kept on PD therapy for 6.4±2.7 years, since the beginning of diagnosis, have maintained normal linear growth. No difference in BMI, HOMA-IR, or CIMT was detected among the two treated groups. The efficiency, safety and convenience of a single daily dose of PD could be a good and relatively safe alternative to HC for the continuing medical treatment of patients with CAH-21OHD. However, more prospective studies across childhood and adolescence are necessary to draw definitive conclusions.
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Obstructive Sleep Apnea Dynamically Increases Nocturnal Plasma Free Fatty Acids, Glucose, and Cortisol During Sleep.
Chopra, S, Rathore, A, Younas, H, Pham, LV, Gu, C, Beselman, A, Kim, IY, Wolfe, RR, Perin, J, Polotsky, VY, et al
The Journal of clinical endocrinology and metabolism. 2017;(9):3172-3181
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Abstract
CONTEXT Obstructive sleep apnea (OSA) is associated with diabetes and cardiovascular disease. This association may be related to metabolic changes that transpire during sleep in OSA. OBJECTIVE To examine the impact of OSA, elicited by cessation of continuous positive airway pressure (CPAP), on frequently sampled nocturnal metabolic markers including plasma free fatty acids (FFAs), glucose, insulin, triglycerides (TGs), cortisol, and lactate, as well as glucose production, oral glucose tolerance, blood pressure (BP), endothelial function, cholesterol, and high-sensitivity C-reactive protein (hsCRP). DESIGN AND SETTING Randomized crossover trial of CPAP vs CPAP withdrawal. PATIENTS Thirty-one patients with moderate to severe OSA acclimated to CPAP. INTERVENTION Patients underwent attended polysomnography while sleeping with therapeutic CPAP, or after CPAP withdrawal, in random order. Venous blood was sampled at ∼20-minute intervals on both nights. In 11 patients, we assessed glucose kinetics with an infusion of 6,6-[2H2]glucose. RESULTS CPAP withdrawal caused recurrence of OSA associated with hypoxemia, sleep disruption, and heart rate (HR) elevation. CPAP withdrawal dynamically increased nocturnal FFA (P = 0.007), glucose (P = 0.028), and cortisol (P = 0.037), in proportion to respiratory event frequency, HR elevation, or sleep fragmentation. Diabetes predisposed to glucose elevation. CPAP withdrawal also increased systolic BP (P = 0.017) and augmentation index (P = 0.008), but did not affect insulin, TGs, glucose production, oral glucose tolerance, cholesterol, or hsCRP. CONCLUSION OSA recurrence during CPAP withdrawal increases FFA and glucose during sleep, associated with sympathetic and adrenocortical activation. Recurring exposure to these metabolic changes may foster diabetes and cardiovascular disease.
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Evaluation of efficacy of aloe vera in the treatment of oral submucous fibrosis - a clinical study.
Anuradha, A, Patil, B, Asha, VR
Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology. 2017;(1):50-55
Abstract
BACKGROUND Oral submucous fibrosis is a chronic disease, treatment of which has largely been symptomatic. Aloe vera has immunomodulatory, anti-inflammatory, wound healing, antioxidant, and antineoplastic activities. All such properties of aloe vera suggest the possibility of its use in the management of oral submucous fibrosis. METHODS Seventy-four patients of oral submucous fibrosis were randomly divided into 2 groups. Group A patients were treated with systemic (juice) and topical aloe vera (gel) for 3 months. Group B patients were treated with intralesional injection of hydrocortisone and hyaluronidase for 6 weeks with antioxidant supplements for 3 months. Patients were assessed for reduction in burning sensation and increase in mouth opening, cheek flexibility, and tongue protrusion at an interval of 1, 2, and 3 months. RESULTS Both the groups showed statistically significant improvements in all the study parameters at the end of study period (P < 0.001). The clinical response to aloe vera was comparable to that of intralesional injections of hydrocortisone and hyaluronidase with antioxidant supplementation. CONCLUSION The study concludes that aloe vera can be an alternative, safe, and effective treatment regime in the management of oral submucous fibrosis. Long-term follow-up studies with larger sample size are recommended.
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Late-Pregnancy Salivary Cortisol Concentrations of Ghanaian Women Participating in a Randomized Controlled Trial of Prenatal Lipid-Based Nutrient Supplements.
Oaks, BM, Laugero, KD, Stewart, CP, Adu-Afarwuah, S, Lartey, A, Ashorn, P, Vosti, SA, Dewey, KG
The Journal of nutrition. 2016;(2):343-52
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BACKGROUND High circulating cortisol is associated with miscarriage, preterm birth, and low birth weight. Research in nonpregnant individuals suggests that improved nutrition may lower cortisol concentrations. It is unknown whether nutritional supplementation during pregnancy lowers cortisol. OBJECTIVE Our objective was to determine whether women receiving a lipid-based nutrient supplement (LNS) throughout pregnancy would have lower salivary cortisol at 36 wk gestation compared with women receiving other nutrient supplements. METHODS We conducted a randomized controlled trial in 1320 pregnant Ghanaian women at ≤20 wk gestation who were assigned to receive daily throughout pregnancy: 1) 60 mg iron + 400 μg folic acid (IFA), 2) multiple micronutrients (MMNs), or 3) 20 g LNS (containing 118 kcal, 22 micronutrients, and protein). Morning salivary cortisol was collected from a subsample at baseline and at 28 and 36 wk gestation. RESULTS A total of 758 women had cortisol measurements at 28 or 36 wk gestation. Salivary cortisol at 36 wk gestation did not differ between groups and was (mean ± SE) 7.97 ± 0.199 in the IFA group, 7.84 ± 0.191 in the MMN group, and 7.77 ± 0.199 nmol/L in the LNS group, when adjusted for baseline cortisol, time of waking, and time between waking and saliva collection (P = 0.67). There was an interaction between supplementation group and women's age (continuous variable, P-interaction = 0.03); and when age was dichotomized by the median, significant differences in salivary cortisol concentrations between groups were seen in women ≤26 y of age (IFA = 8.23 ± 0.284 nmol/L, MMN = 8.20 ± 0.274 nmol/L, and LNS = 7.44 ± 0.284 nmol/L; P = 0.03) but not in women >26 y old (IFA = 7.71 ± 0.281 nmol/L, MMN = 7.50 ± 0.274 nmol/L, and LNS = 8.08 ± 0.281 nmol/L; P = 0.13). CONCLUSIONS We conclude that supplementation with LNSs or MMNs during pregnancy did not affect the cortisol concentration in the study population as a whole, in comparison with IFA, but that LNS consumption among younger women may lead to lower cortisol at 36 wk gestation. This trial was registered at clinicaltrials.gov as NCT00970866.
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Accuracy of immunoassay and mass spectrometry urinary free cortisol in the diagnosis of Cushing's syndrome.
Aranda, G, Careaga, M, Hanzu, FA, Patrascioiu, I, Ríos, P, Mora, M, Morales-Romero, B, Jiménez, W, Halperin, I, Casals, G
Pituitary. 2016;(5):496-502
Abstract
PURPOSE Urinary free cortisol (UFC) determination by highly specific methods as mass spectrometry instead of commercially available antibody-based immunoassays is increasingly recommended. However, clinical comparisons of both analytical approaches in the screening of Cushing's syndrome (CS) are not available. The aim of this study was to evaluate the diagnostic value of mass spectrometry versus immunoassay measurements of 24 h-UFC in the screening of CS. METHODS Cross-sectional study of 33 histologically confirmed CS patients: 25 Cushing's disease, 5 adrenal CS and 3 ectopic CS; 92 non-CS patients; and 35 healthy controls. UFC by immunoassay (UFCxIA) and mass spectrometry (UFCxMS), urinary free cortisone (UFCo) and UFC:UFCo ratio were measured, together with creatinine-corrected values. Sensitivity, specificity, AUC and Landis and Koch concordance index were determined. RESULTS AUC for UFCxIA and UFCxMS were 0.77 (CI 0.68-0.87) and 0.77 (CI 0.67-0.87) respectively, with a kappa coefficient 0.60 and strong Landis and Koch concordance index. The best calculated cutoff values were 359 nmol/24 h for UFCxIA (78 % sensitivity, 62 % specificity) and 258.1 nmol/24 h for UCFxMS (53 % sensitivity, 86 % specificity). The upper limit of UFCxIA and UCFxMS reference ranges were 344.7 and 169.5 nmol/24 h respectively. Sensitivity and specificity for CS diagnosis at these cutpoints were 84 and 56 % for UFCxIA and 81 and 54 % for UFCxMS. CONCLUSIONS According to our data, both methods present a very similar diagnostic value. However, results suggest that lower cutoff points for mass spectrometry may be necessary in order to improve clinical sensitivity.
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Cortisol, blood pressure, and heart rate responses to food intake were independent of physical fitness levels in women.
Jayasinghe, SU, Torres, SJ, Fraser, SF, Turner, AI
Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme. 2015;(11):1186-92
Abstract
This research tested the hypothesis that women who had higher levels of physical fitness will have lower hypothalamo-pituitary-adrenal axis (cortisol) and sympatho-adrenal medullary system (blood pressure and heart rate) responses to food intake compared with women who had low levels of physical fitness. Lower fitness (n = 22; maximal oxygen consumption = 27.4 ± 1.0 mL∙kg(-1)·min(-1)) and higher fitness (n = 22; maximal oxygen consumption = 41.9 ± 1.6 mL∙kg(-1)·min(-1)) women (aged 30-50 years; in the follicular phase of the menstrual cycle) who participated in levels of physical activity that met (lower fitness = 2.7 ± 0.5 h/week) or considerably exceeded (higher fitness = 7.1 ± 1.4 h/week) physical activity guidelines made their own lunch using standardised ingredients at 1200 h. Concentrations of cortisol were measured in blood samples collected every 15 min from 1145-1400 h. Blood pressures and heart rate were also measured every 15 min between 1145 h and 1400 h. The meal consumed by the participants consisted of 20% protein, 61% carbohydrates, and 19% fat. There was a significant overall response to lunch in all of the parameters measured (time effect for all, p < 0.01). The cortisol response to lunch was not significantly different between the groups (time × treatment, p = 0.882). Overall, both groups showed the same pattern of cortisol secretion (treatment p = 0.839). Systolic blood pressure, diastolic blood pressure, mean arterial pressure, or heart rate responses (time × treatment, p = 0.726, 0.898, 0.713, and 0.620, respectively) were also similar between higher and lower fitness women. Results suggest that the physiological response to food intake in women is quite resistant to modification by elevated physical fitness levels.
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Effects of preemptive analgesia with parecoxib sodium on haemodynamics and plasma stress hormones in surgical patients with thyroid carcinoma.
Wang, LD, Gao, X, Li, JY, Yu, HY, Su, HW, Liu, LZ, Qi, J
Asian Pacific journal of cancer prevention : APJCP. 2015;(9):3977-80
Abstract
BACKGROUND To investigate the effects of preemptive analgesia with parecoxib sodium on haemodynamics and plasma stress hormones in surgical patients with thyroid carcinoma. MATERIALS AND METHODS Fifty-seven patients with thyroid carcinoma who underwent thyroidectomy selectively in Laiwu Hospital Affiliated to Taishan Medical University and Binzhou People's Hospital were selected and randomly divided into three groups, 19 cases in each group. The control group was intravenously injected 0.9% sodium chloride injection before anesthesia induction; trial group I was intravenously injected with parecoxib sodium 20 min before anesthesia induction; based on trial group I, trial group II was injected with parecoxib sodium again 12 h after surgery. The levels of plasma norepinephrine (NE), cortisol (Cor) and blood glucose before, 12 and 24 h after surgery and changes of haemodynamics before surgery, at the end of surgery and 12, 24 and 48 h after surgery were compared in the three groups. Besides, visual analogue scale (VAS) scores were recorded 4, 8, 12 and 24 h after surgery. RESULTS 12 and 24 h after surgery, the levels of plasma NE and Cor in three groups rose dramatically (P<0.05 or (P<0.01); The levels of plasma NE and Cor in trial groups I and II were evidently lower than in control group (P<0.05 or P<0.01), and those in trial group II slightly lower than in trial group I. 12 h after surgery, the heart rates (HR) and systolic pressures (SBP) in trial groups I and II increased obviously by comparison to surgery before (P<0.05 or P<0.01), but gradually returned to the preoperative level. HR, SBP and diastolic pressures (DBP) in trial groups I and II at the end of surgery and 12 h after surgery were all lower than in the control group, and significant differences were present (P<0.05 or (P<0.01). At 4, 8, 12 and 24 h after surgery, VAS scores in trial groups I and II were markedly lower than in the control group ((P<0.05 or (P<0.01), the scores in trial group II being the lowest. CONCLUSIONS Combined application of parecoxib sodium for preemptive analgesia before anesthesia and after surgery can effectively reduce the levels of plasma stress hormones and improve analgesic effects in surgical patients with thyroid carcinoma, and without conspicuous impact on haemodynamics.
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Effect of cortisol and/or DHEA on THP1-derived macrophages infected with Mycobacterium tuberculosis.
Bongiovanni, B, Mata-Espinosa, D, D'Attilio, L, Leon-Contreras, JC, Marquez-Velasco, R, Bottasso, O, Hernandez-Pando, R, Bay, ML
Tuberculosis (Edinburgh, Scotland). 2015;(5):562-9
Abstract
Tuberculosis (TB) is a major health problem requiring an appropriate cell immune response to be controlled. Macrophages play a central role in the response against Mycobacterium tuberculosis (Mtb). Given our prior studies in which adrenal steroids were found to modify the cellular immune responses from TB patients, it was sensible to analyze the immunomodulatory capability of cortisol and DHEA on macrophages infected with Mtb. The human macrophage-like THP-1 cells were infected with the H37Rv strain of Mtb and treated with Cortisol and DHEA at different doses. We monitored phagocytosis, intracellular-bacterial growth, autophagosoma formation, as well as cytokine gene expression and production. Cultures exposed to cortisol showed a decreased production of IL-1β, TNF-α, with DHEA being unable to modify the pattern of cytokine production or to reverse the cortisol inhibitory effects. Interestingly the intra-macrophagic bacterial burden was found reduced by DHEA treatment. While this effect was not related to a different cytokine pattern, in terms their production or mRNA expression, DHEA treatment did promote autophagy in Mtb-infected macrophages, irrespective of Cortisol presence. In essence, the better control of Mtb load by DHEA-treated macrophages seems to be dependent on an autophagic mechanism. The present results are relevant for two reasons as autophagy is not only important for clearance of mycobacteria but also for the prevention of tissue damage.
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Body composition and power performance improved after weight reduction in male athletes without hampering hormonal balance.
Huovinen, HT, Hulmi, JJ, Isolehto, J, Kyröläinen, H, Puurtinen, R, Karila, T, Mackala, K, Mero, AA
Journal of strength and conditioning research. 2015;(1):29-36
Abstract
The aim of this study was to investigate the effects of a 4-week weight reduction period with high protein and reduced carbohydrate intake on body composition, explosive power, speed, serum hormones, and acid-base balance in male track and field jumpers and sprinters. Eight participants were assigned to a high weight reduction group (HWR; energy restriction 750 kcal·d) and 7 to a low weight reduction group (LWR; energy restriction 300 kcal·d). Energy and carbohydrate intake decreased significantly (p ≤ 0.05) only in HWR by 740 ± 330 kcal·d and 130 ± 29 g·d, respectively. Furthermore, total body mass and fat mass decreased (p ≤ 0.05) only in HWR by 2.2 ± 1.0 kg and 1.7 ± 1.6 kg, respectively. Fat-free mass (FFM), serum testosterone, cortisol, and sex hormone-binding globulin did not change significantly. Ca ion and pH decreased (p ≤ 0.05) only in HWR (3.1 ± 2.8% and 0.8 ± 0.8%, respectively), whereas (Equation is included in full-text article.)declined (p ≤ 0.05) in both groups by 19.3 ± 6.2% in HWR and by 13.1 ± 8.5% in LWR. The countermovement jump and 20-m sprint time improved consistently (p ≤ 0.05) only in HWR, by 2.6 ± 2.5 cm and 0.04 ± 0.04 seconds, respectively. Finally, athletes with a fat percentage of 10% or more at the baseline were able to preserve FFM. In conclusion, altered acid-base balance but improved weight-bearing power performance was observed without negative consequences on serum hormones and FFM after a 4-week weight reduction of 0.5 kg·wk achieved by reduced carbohydrate but maintained high protein intake.