Adrenocorticotropic hormone (ACTH) level and adrenal deficiency in patients with mucocutaneous pemphigus.

OBJECTIVES: This study aimed to evaluate the level of adrenocorticotropic hormone (ACTH) and adrenal insufficiency in patients with mucocutaneous pemphigus lesions who use oral corticosteroids. METHODS: This descriptive-analytical study was performed on 54 patients (48.44 ± 12.74 years) with mucocutaneous pemphigus in 2019. Those patients taken corticosteroids in different doses and way. At first, collected patients information including age, sex, type of pemphigus, duration of use, patient dosage, duration of corticosteroid administration, and method of administration were collected daily. Adrenal gland function was measured by evaluating ACTH levels. Data were analyzed by using Pearson correlation coefficient and t-test. RESULTS: Our study showed that 37 cases (68.5%) had normal ACTH average hormone level (7.3-63.3 mL/pg), 11 cases (20.4%) were lower levels (<7.2 mL/pg), and 6 cases (11.1%) were higher levels (63.3 > mL/pg). Wo observed no significant relationship between ACTH and duration of corticosteroids usage (p=0.207). CONCLUSIONS: Taking a maintenance dose of between 12.5 and 25 mg daily does not usually lead to adrenal insufficiency. The present study showed that the lower the daily dose of corticosteroids, the lower the likelihood of adrenal insufficiency.

Callous unemotional trait-like mice and their stressed dams.

The co-occurrence of excess rates of aggression, general violation of societal norms and callous-unemotional trait confers specific risk for adult psychopathy. With the aim to address experimentally a model of conduct disorder, we investigated the male offspring of individual mouse dams characterized by high basal plasma corticosterone concentration (HC trait). Notably, classification indices correlated selectively in these females with quite poor maternal care devoted to their offspring. Contrary to their HC mothers, adult male offspring exhibited an integrated profile of dampened physiological reactivity to external stressors co-occurring poor sociability/emotional contagion, impaired punishment-induced memory, and exacerbated aggression. A significant reduction of glucocorticoid and opioid mu receptors' expression in frontal cortex of model HC offspring was also evidenced. Moreover, in the absence of changes in oxytocin receptor in behaviorally-relevant neural areas, we showed that intranasal oxytocin administration (0 or 20.0 µg/kg) selectively modulated specific components of the behavioral phenotype. Ultimately, current data support the notion that maternally-inoculated environmental stress early in development may represent a critical risk factor in disturbances characterised by abnormal aggression and excess callousness.

Variation in the SERPINA6/SERPINA1 locus alters morning plasma cortisol, hepatic corticosteroid binding globulin expression, gene expression in peripheral tissues, and risk of cardiovascular disease.

The stress hormone cortisol modulates fuel metabolism, cardiovascular homoeostasis, mood, inflammation and cognition. The CORtisol NETwork (CORNET) consortium previously identified a single locus associated with morning plasma cortisol. Identifying additional genetic variants that explain more of the variance in cortisol could provide new insights into cortisol biology and provide statistical power to test the causative role of cortisol in common diseases. The CORNET consortium extended its genome-wide association meta-analysis for morning plasma cortisol from 12,597 to 25,314 subjects and from ~2.2 M to ~7 M SNPs, in 17 population-based cohorts of European ancestries. We confirmed the genetic association with SERPINA6/SERPINA1. This locus contains genes encoding corticosteroid binding globulin (CBG) and α1-antitrypsin. Expression quantitative trait loci (eQTL) analyses undertaken in the STARNET cohort of 600 individuals showed that specific genetic variants within the SERPINA6/SERPINA1 locus influence expression of SERPINA6 rather than SERPINA1 in the liver. Moreover, trans-eQTL analysis demonstrated effects on adipose tissue gene expression, suggesting that variations in CBG levels have an effect on delivery of cortisol to peripheral tissues. Two-sample Mendelian randomisation analyses provided evidence that each genetically-determined standard deviation (SD) increase in morning plasma cortisol was associated with increased odds of chronic ischaemic heart disease (0.32, 95% CI 0.06-0.59) and myocardial infarction (0.21, 95% CI 0.00-0.43) in UK Biobank and similarly in CARDIoGRAMplusC4D. These findings reveal a causative pathway for CBG in determining cortisol action in peripheral tissues and thereby contributing to the aetiology of cardiovascular disease.

Immune variations throughout the course of tuberculosis treatment and its relationship with adrenal hormone changes in HIV-1 patients co-infected with Mycobacterium tuberculosis.

HIV infection is a major risk factor predisposing for Mycobacterium tuberculosis infection and progression to active tuberculosis (TB). As host immune response defines the course of infection, we aimed to identify immuno-endocrine changes over six-months of anti-TB chemotherapy in HIV+ people. Plasma levels of cortisol, DHEA and DHEA-S, percentages of CD4+ regulatory T cell subsets and number of IFN-γ-secreting cells were determined. Several cytokines, chemokines and C-reactive protein levels were measured. Results were correlated with clinical parameters as predictors of infection resolution and compared to similar data from HIV+ individuals, HIV-infected persons with latent TB infection and healthy donors. Throughout the course of anti-TB/HIV treatment, DHEA and DHEA-S plasma levels raised while cortisol diminished, which correlated to predictive factors of infection resolution. Furthermore, the balance between cortisol and DHEA, together with clinical assessment, may be considered as an indicator of clinical outcome after anti-TB treatment in HIV+ individuals. Clinical improvement was associated with reduced frequency of unconventional Tregs, increment in IFN-γ-secreting cells, diminution of systemic inflammation and changes of circulating cytokines and chemokines. This study suggests that the combined anti-HIV/TB therapies result in partial restoration of both, immune function and adrenal hormone plasma levels.

Bifidobacterium longum counters the effects of obesity: Partial successful translation from rodent to human.

BACKGROUND: The human gut microbiota has emerged as a key factor in the development of obesity. Certain probiotic strains have shown anti-obesity effects. The objective of this study was to investigate whether Bifidobacterium longum APC1472 has anti-obesity effects in high-fat diet (HFD)-induced obese mice and whether B. longum APC1472 supplementation reduces body-mass index (BMI) in healthy overweight/obese individuals as the primary outcome. B. longum APC1472 effects on waist-to-hip ratio (W/H ratio) and on obesity-associated plasma biomarkers were analysed as secondary outcomes. METHODS: B. longum APC1472 was administered to HFD-fed C57BL/6 mice in drinking water for 16 weeks. In the human intervention trial, participants received B. longum APC1472 or placebo supplementation for 12 weeks, during which primary and secondary outcomes were measured at the beginning and end of the intervention. FINDINGS: B. longum APC1472 supplementation was associated with decreased bodyweight, fat depots accumulation and increased glucose tolerance in HFD-fed mice. While, in healthy overweight/obese adults, the supplementation of B. longum APC1472 strain did not change primary outcomes of BMI (0.03, 95% CI [-0.4, 0.3]) or W/H ratio (0.003, 95% CI [-0.01, 0.01]), a positive effect on the secondary outcome of fasting blood glucose levels was found (-0.299, 95% CI [-0.44, -0.09]). INTERPRETATION: This study shows a positive translational effect of B. longum APC1472 on fasting blood glucose from a preclinical mouse model of obesity to a human intervention study in otherwise healthy overweight and obese individuals. This highlights the promising potential of B. longum APC1472 to be developed as a valuable supplement in reducing specific markers of obesity. FUNDING: This research was funded in part by Science Foundation Ireland in the form of a Research Centre grant (SFI/12/RC/2273) to APC Microbiome Ireland and by a research grant from Cremo S.A.

Discrepancies in the Recommended Management of Adrenal Incidentalomas by Various Guidelines.

PURPOSE: Adrenal incidentalomas are being discovered with increasing frequency, and their discovery poses a challenge to clinicians. Despite the 2002 National Institutes of Health consensus statement, there are still discrepancies in the most recent guidelines from organizations representing endocrinology, endocrine surgery, urology and radiology. We review recent guidelines across the specialties involved in diagnosing and treating adrenal incidentalomas, and discuss points of agreement as well as controversy among guidelines. MATERIALS AND METHODS: PubMed®, Scopus®, Embase™ and Web of Science™ databases were searched systematically in November 2019 in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement to identify the most recently updated committee produced clinical guidelines in each of the 4 specialties. Five articles met the inclusion criteria. RESULTS: There is little debate among the reviewed guidelines as to the initial evaluation of an adrenal incidentaloma. All patients with a newly discovered adrenal incidentaloma should receive an unenhanced computerized tomogram and hormone screen. The most significant points of divergence among the guidelines regard reimaging an initially benign appearing mass, repeat hormone testing and management of an adrenal incidentaloma that is not easily characterized as benign or malignant on computerized tomography. The guidelines range from actively recommending against any repeat imaging and hormone screening to recommending a repeat scan as early as in 3 to 6 months and annual hormonal screening for several years. CONCLUSIONS: After reviewing the guidelines and the evidence used to support them we posit that best practices lie at their convergence and have presented our management recommendations on how to navigate the guidelines when they are discrepant.

Effects of physiological changes and social life events on adrenal glucocorticoid activity in female zoo-housed Asian elephants (Elephas maximus).

Ensuring good health and welfare is an increasingly important consideration for conservation of endangered species and includes breeding of individuals managed under human care. Understanding how factors in the captive environment affect individual animal wellbeing can be aided by long-term monitoring of biological functioning. This study involved longitudinal assessments (4 to 28 years) of reproductive and adrenal hormones in zoo-housed female Asian elephants (Elephas maximus) (age range 4 to ~71 years) to elucidate patterns in adrenal glucocorticoid (GC) activity in association with reproductive and demographic factors, and examine individual response to major social changes. Concentrations of serum and urinary cortisol covaried more consistently with physiological changes (ovarian cycle phase, puberty, pregnancy, lactational anestrus, and age) than with social life events (births, deaths, and facility transfers). Cortisol fluctuated across the ovarian cycle with mean concentrations being higher in the follicular than in the luteal phase, and concentrations were highest in lactational anestrous compared to all other reproductive states. The elephants in this study exhibited substantial individuality in adrenal GC response to major social change, reinforcing the need to assess welfare on an individual basis and to consider factors influencing the impact of perceived stressors, such as social relationships, social support, temperament, and life history. Outcomes from this study deepen our understanding of Asian elephant physiology and highlight the importance of taking intrinsic patterns of hormone secretion into account when evaluating the impact of external factors. Finally, a better understanding of the impact of social change and resiliency in response to real and perceived stressors allows us to improve social management to enhance welfare in both captive settings and free-ranging environments.

Lipid metabolism is associated with temperament, corticosteroid, and hematological measures in infant rhesus monkeys ( Macaca mulatta).

Individuals can differ in how their behavioral and physiological systems are organized. The fact that these individual differences persist across life suggests they are supported by physical structures that may co-vary. Here, we explored three datasets associated with health and behavioral outcomes, which were obtained from infant rhesus monkeys during standardized assessment of biobehavioral organization. Variation in biobehavioral measures was related to variation in molecular pathways, as assessed by metabolomics. Plasma from infant male rhesus monkeys ( Macaca mulatta) ( n=52) was subjected to metabolite profiling. Principal component analyses identified multiple factors that explained 60%-80% of the variance in the metabolite measures. Correlational and regression analyses of corticosteroid, hematological, and temperament measures revealed significant relationships with indicators of lipid metabolism. Significant relationships were found for cortisol responses to stress and adrenocorticotropin (ACTH) stimulation, indicators of innate immunity (monocytes and natural killer (NK) cells), hemoglobin/hematocrit, and three measures of temperament. It will be important to replicate this first-of-a-kind study to determine whether the relationship between measures of biobehavioral organization and lipid metabolism are a general result, or one that is specific to early development.

SOURCE: a phase 3, multicentre, randomized, double-blind, placebo-controlled, parallel group trial to evaluate the efficacy and safety of tezepelumab in reducing oral corticosteroid use in adults with oral corticosteroid dependent asthma.

BACKGROUND: Many patients with severe asthma continue to experience asthma symptoms and exacerbations despite standard-of-care treatment. A substantial proportion of these patients require long-term treatment with oral corticosteroids (OCS), often at high doses, which are associated with considerable multiorgan adverse effects, including metabolic disorders, osteoporosis and adrenal insufficiency. Tezepelumab is a human monoclonal antibody that blocks the activity of the epithelial cytokine thymic stromal lymphopoietin. In the PATHWAY phase 2b study (NCT02054130), tezepelumab significantly reduced exacerbations by up to 71% in adults with severe, uncontrolled asthma. Several ongoing phase 3 trials (SOURCE, NCT03406078; NAVIGATOR, NCT03347279; DESTINATION, NCT03706079) are assessing the efficacy and safety of tezepelumab in patients with severe, uncontrolled asthma. Here, we describe the design and objectives of SOURCE, a phase 3 OCS-sparing study. METHODS: SOURCE is an ongoing phase 3, multicentre, randomized, double-blind, placebo-controlled study to evaluate the effect of tezepelumab 210 mg administered subcutaneously every 4 weeks on OCS dose reduction in adults with OCS-dependent asthma. The study comprises a 2-week screening and enrolment period, followed by an OCS optimization phase of up to 8 weeks and a 48-week treatment period, which consists of a 4-week induction phase, followed by a 36-week OCS reduction phase and an 8-week maintenance phase. The primary objective is to assess the effect of tezepelumab compared with placebo in reducing the prescribed OCS maintenance dose. The key secondary objective is to assess the effect of tezepelumab on asthma exacerbation rates. Other secondary objectives include the proportion of patients with a reduction in OCS dose (100% or 50% reduction or those receiving < 5 mg) and the effect of tezepelumab on lung function and patient-reported outcomes. CONCLUSIONS: SOURCE is evaluating the OCS-sparing potential of tezepelumab in patients with OCS-dependent asthma. SOURCE also aims to demonstrate that treatment with tezepelumab in patients with severe asthma is associated with reductions in exacerbation rates and improvements in lung function, asthma control and health-related quality of life, while reducing OCS dose. TRIAL REGISTRATION: NCT03406078 ( ClinicalTrials.gov ). Registered 23 January 2018. https://clinicaltrials.gov/ct2/show/NCT03406078.

Impact of three commonly used blood sampling techniques on the welfare of laboratory mice: Taking the animal's perspective.

Laboratory mice are the most frequently used animals in biomedical research. In accordance with guidelines for humane handling, several blood sampling techniques have been established. While the effects of these procedures on blood quality and histological alterations at the sampling site are well studied, their impact on the animals' welfare has not been extensively investigated. Therefore, our study aimed to compare three commonly used blood sampling techniques regarding their effects on different indicators of animal welfare, including physiological and behavioural response stress parameters, including pain measures, home-cage behaviour and nest-building as well as exploratory activity and neophobia. Male C57BL/6J mice were subjected to a single blood collection from either the vena facialis, the retrobulbar sinus or the tail vessel, or were allocated to the respective control treatment. While all blood sampling techniques led to an acute increase in plasma corticosterone levels, the response was strongest in animals that underwent sampling from the vena facialis and the retrobulbar sinus. Similar results were observed when the time-course of adrenocortical activity was monitored via corticosterone metabolites from faecal samples. Blood collection from the vena facialis and the retrobulbar sinus also decreased exploration of novel stimuli, resulted in decreased nest-building activity and induced higher scores in the Mouse Grimace Scale. Moreover, locomotor activity and anxiety-related behaviour were strongly affected after facial vein bleeding. Interestingly, tail vessel bleeding only induced little alterations in the assessed physiological and behavioural parameters. Importantly, the observed effects in all treatment groups were no longer detectable after 24 hours, indicating only short-term impacts. Thus, by also taking the animal's perspective and comprehensively assessing the severity of the particular sampling procedures, the results of our study contribute to Refinement within the 3R concept and allow researchers to objectively select the most appropriate and welfare-friendly blood sampling technique for a given experiment.

Inferior Adrenal Artery PI in Fetuses with IUGR: Value Indicating Early Blood Redistribution and Steroidogenic Response.

OBJECTIVE: To characterize the inferior adrenal artery (IAA) pulsatility index (PI) in intrauterine growth-restricted (IUGR) fetuses without brain sparing. METHODS: Twenty-three IUGR fetuses with a normal Doppler cerebroplacental ratio (CPR) and 23 normal controls were included in this prospective cross-sectional study. The PI of the IAA was recorded using routine transabdominal Doppler ultrasound. The differences in Doppler characteristics, perinatal outcomes, and steroidogenesis in the umbilical vein at birth (adrenocorticotropic hormone [ACTH] and cortisol [F] levels) were compared between the 2 groups. The correlations between IAA-PI and steroidogenesis were assessed in the IUGR group. RESULTS: IAA-PI was significantly lower in IUGR fetuses than in normal controls (0.85 vs 1.18 at first scan, 0.78 vs 0.92 at last scan; both P < 0.001). The plasma F and ACTH levels in IUGR cases were significantly higher than those of the normal controls (18.2 vs 12.4 µg/dL and 280.5 vs 125.6 pg/mL for F and ACTH, respectively; both P < 0.001). There were negative correlations between IAA-PI and plasma F values and between IAA-PI and ACTH values in the IUGR group (r = -0.774 and -0.82 at first scan, r = -0.525 and -0.45 at last scan, respectively; P < 0.001). CONCLUSION: Increased adrenal gland blood flow with concomitant increases in ACTH and F levels were observed in IUGR fetuses. IAA-PI is useful to assess early blood redistribution and may be beneficial for evaluating the steroidogenic response in high-risk pregnancies.

Hormonal determinants of mammographic density and density change.

BACKGROUND: Mammographic density (MD) is a strong risk factor for breast cancer. We examined how endogenous plasma hormones are associated with average MD area (cm2) and annual MD change (cm2/year). METHODS: This study within the prospective KARMA cohort included analyses of plasma hormones of 1040 women. Hormones from the progestogen (n = 3), androgen (n = 7), oestrogen (n = 2) and corticoid (n = 5) pathways were analysed by ultra-performance supercritical fluid chromatography-tandem mass spectrometry (UPSFC-MS/MS), as well as peptide hormones and proteins (n = 2). MD was measured as a dense area using the STRATUS method (mean over the left and right breasts) and mean annual MD change over time. RESULTS: Greater baseline mean MD was associated with overall higher concentrations of progesterone (average + 1.29 cm2 per doubling of hormone concentration), 17OH-progesterone (+ 1.09 cm2), oesterone sulphate (+ 1.42 cm2), prolactin (+ 2.11 cm2) and SHBG (+ 4.18 cm2), and inversely associated with 11-deoxycortisol (- 1.33 cm2). The association between MD and progesterone was confined to the premenopausal women only. The overall annual MD change was - 0.8 cm2. Hormones from the androgen pathway were statistically significantly associated with MD change. The annual MD change was - 0.96 cm2 and - 1.16 cm2 lesser, for women in the highest quartile concentrations of testosterone and free testosterone, respectively, compared to those with the lowest concentrations. CONCLUSIONS: Our results suggest that, whereas hormones from the progestogen, oestrogen and corticoid pathways drive baseline MD, MD change over time is mainly driven by androgens. This study emphasises the complexity of risk factors for breast cancer and their mechanisms of action.

Residual Corticosteroid Production in Autoimmune Addison Disease.

CONTEXT: Contrary to current dogma, growing evidence suggests that some patients with autoimmune Addison disease (AAD) produce corticosteroids even years after diagnosis. OBJECTIVE: To determine frequencies and clinical features of residual corticosteroid production in patients with AAD. DESIGN: Two-staged, cross-sectional clinical study in 17 centers (Norway, Sweden, and Germany). Residual glucocorticoid (GC) production was defined as quantifiable serum cortisol and 11-deoxycortisol and residual mineralocorticoid (MC) production as quantifiable serum aldosterone and corticosterone after > 18 hours of medication fasting. Corticosteroids were analyzed by liquid chromatography-tandem mass spectrometry. Clinical variables included frequency of adrenal crises and quality of life. Peak cortisol response was evaluated by a standard 250 µg cosyntropin test. RESULTS: Fifty-eight (30.2%) of 192 patients had residual GC production, more common in men (n = 33; P < 0.002) and in shorter disease duration (median 6 [0-44] vs 13 [0-53] years; P < 0.001). Residual MC production was found in 26 (13.5%) patients and associated with shorter disease duration (median 5.5 [0.5-26.0] vs 13 [0-53] years; P < 0.004), lower fludrocortisone replacement dosage (median 0.075 [0.050-0.120] vs 0.100 [0.028-0.300] mg; P < 0.005), and higher plasma renin concentration (median 179 [22-915] vs 47.5 [0.6-658.0] mU/L; P < 0.001). There was no significant association between residual production and frequency of adrenal crises or quality of life. None had a normal cosyntropin response, but peak cortisol strongly correlated with unstimulated cortisol (r = 0.989; P < 0.001) and plasma adrenocorticotropic hormone (ACTH; r = -0.487; P < 0.001). CONCLUSION: In established AAD, one-third of the patients still produce GCs even decades after diagnosis. Residual production is more common in men and in patients with shorter disease duration but is not associated with adrenal crises or quality of life.

Mean platelet volume and response to the first line therapy in newly diagnosed adult immune thrombocytopenia patients: a retrospective study

Background/aim: Immune thrombocytopenia (ITP) is treated by corticosteroids and/or intravenous immune globulin as the first line treatment when necessary. Mean platelet volume (MPV) is a marker of platelet production and function. In this study, we aimed to search the relationship between the MPV and the treatment response in ITP patients and it was hypothesized that MPV can be used as a predictor of the response. Materials and methods: The 70 newly diagnosed adult primary ITP patients and 70 of healthy people were included. MPV between ITP and healthy population, MPV in the diagnosis and after the treatment between the responders and the nonresponders were compared. Results: The responders had significantly higher MPV and the nonresponders had significantly lower MPV than the healthy population (11.09 and 10.21 fL, P = 0.03; 9.38 and 10.21 fL, P = 0.001). MPV in the diagnosis was significantly higher in the responders than the nonresponders (11.09 and 9.38 fL, P = 0.005). MPV significantly changed after the treatment in the responders (11.09 to 9.32 fL, P = 0.004). Conclusion: MPV can be used as a predictor of early response to the first line treatment in newly diagnosed adult primary ITP patients.

Hippocampal CCR5/RANTES Elevations in a Rodent Model of Post-Traumatic Stress Disorder: Maraviroc (a CCR5 Antagonist) Increases Corticosterone Levels and Enhances Fear Memory Consolidation.

BACKGROUND: Contextual fear conditioning (CFC) is a rodent model that induces a high and long-lasting level of conditioning associated with traumatic memory formation; this behavioral paradigm resembles many characteristics of posttraumatic stress disorder (PSTD). Chemokines (chemotactic cytokines) play a known role in neuronal migration and neurodegeneration but their role in cognition is not totally elucidated. AIM: We ascertain whether CCR5/RANTES beta chemokines (hippocampus/prefrontal cortex) could play a role in fear memory consolidation (CFC paradigm). We also evaluated whether chronic stress restraint (21 days of restraint, 6-h/day) could regulate levels of these beta chemokines in CFC-trained rats; fear memory retention was determined taking the level of freezing (context and tone) by the animals as an index of fear memory consolidation 24 h after CFC training session; these chemokines (CCR5/RANTES) and IL-6 levels were measured in the hippocampus and prefrontal cortex of chronically stressed rats, 24 h after CFC post-training, and compared with undisturbed CFC-trained rats (Experiment 1). In Experiment 2, rats received 1 mA of footshock during the CFC training session and fear memory consolidation was evaluated at 12 and 24 h after CFC training sessions. We evaluated whether RANTES levels could be differentially regulated at 12 and 24 h after CFC training; in Experiment 3, maraviroc was administered to rats (i.m: 100 mg/Kg, a CCR5 antagonist) before CFC training. These rats were not subjected to chronic stress restraint. We evaluated whether CCR5 blockade before CFC training could increase corticosterone, RANTES, or IL-6 levels and affects fear memory consolidation in the rats 24-h post-testing compared with vehicle CFC-trained rats. RESULTS: Elevations of CCR5/RANTES chemokine levels in the hippocampus could have contributed to fear memory consolidation (24 h post-training) and chronic stress restraint did not affect these chemokines in the hippocampus; there were no significant differences in CCR5/RANTES levels between stressed and control rats in the prefrontal cortex (Experiment 1). In Experiment 2, hippocampal CCR5/RANTES levels increased and enhanced fear memory consolidation was observed 12 and 24 h after CFC training sessions with 1 mA of footshock. Increased corticosterone and CCR5/RANTES levels, as well as a higher freezing percentage to the context, were found at 24 h CFC post-testing in maraviroc-treated rats as compared to vehicle-treated animals (experiment-3). Conversely, IL-6 is not affected by maraviroc treatment in CFC training. CONCLUSION: Our findings suggest a role for a hippocampal CCR5/RANTES axis in contextual fear memory consolidation; in fact, RANTES levels increased at 12 and 24 h after CFC training. When CCR5 was blocked by maraviroc before CFC training, RANTES (hippocampus), corticosterone levels, and fear memory consolidation were greater than in vehicle CFC-trained rats 24 h after the CFC session.

A clinical audit: diagnostic and epidemiological evaluation of the adrenal incidentaloma.

BACKGROUND: Audit is a clinical instrument of government characterized by a whole process of evaluation inter pares to improve medical behaviors in the clinical practice. Different endocrinopathies are underestimated in the clinical and diagnostics practice but they can be a real problem in patients admitted in the departments of Internal Medicine. The adrenal incidentaloma is an accidental discovery with an incidence equal to 4% in radiologic studies but it's rarely considereted in the internal disorders. In the departments of Internal Medicine are hospitalized each year approximately 1450,000 patients and 58,000 about them show a surrenalic lesion identified with CT or MRI as Adrenal Incidentaloma. METHODS: Through a search in the radiological archives, were reviewed all abdominal CT performed in the year 2012 in 8 departments of Internal Medicine of 8 Italian public hospitals. They also examined all medical records of these patients to value clinical management of the adrenal masses and the real incidence of the adrenal incidentaloma. RESULTS: Distribution of pathological results show an important incidence about adrenal incidentaloma in Italian patients although this pathology is represented as a rare disease and its clinical and economic burden are significant. Many questions remain unanswered as the association between duration and severity of the disease, morbidity and how the dimensions affecting it. These results need to be supported by important studies with long follow-up to realize an easy diagnosis. CONCLUSIONS: The results of this audit confirm the real incidence of this pathology in the internistic patients and the final target is to implement changes about therapeutic diagnostic pathway of the hospital patients in the internal medicine departments.

Acute responses of comprehensive gonadosteroids and corticosteroids to resistance exercise before and after 10 weeks of supervised strength training.

NEW FINDINGS: What is the central question of this study? Although acute responses of the principal gonadosteroid and corticosteroid hormones to resistance exercise are well documented, there is no information regarding how the key lower-concentration intermediary hormones respond and potentially influence these hormonal pathways. What is the main finding and its importance? This study provides evidence for cascading conversions of some gonadosteroids, and the data suggest that the testosterone concentration increases independently of these hormones. These findings challenge future studies to determine the exact physiological roles of the lower-concentration gonadosteroids and corticosteroids during and immediately after resistance exercise. ABSTRACT: Resistance training is a potent stimulus for muscle growth, and steroid hormones are known to play a role in this adaptation. However, very little is known about the acute exercise-induced gonadosteroid and corticosteroid hormone responses, including those of key lower-concentration intermediate hormones. The present study determined the acute responses of these steroid hormone families using quantitative ultra-high performance liquid chromatography tandem mass spectrometry after resistance exercise in strength-trained men. Venous and fingertip blood samples were obtained pre-, mid-, 5 min post- and 15 min post-resistance exercise, both before and after 10 weeks of supervised resistance training. The experimental resistance exercise sessions consisted of three sets of 10 repetitions of bilateral leg-press exercise and three sets of 10 repetitions of unilateral knee-extension exercise, with 2 and 1 min recovery between sets, respectively. Statistically significant (P < 0.05) increases in the concentration of hormones in the gonadosteroid [including dehydroepiandrosterone (DHEA), androstenedione, testosterone and estrone] and the corticosteroid (including cortisol, corticosterone and cortisone) families were demonstrated after both experimental resistance exercise sessions, irrespective of training status. Correlation analyses revealed relationships between the following hormones: (i) DHEA and androstenedione; (ii) DHEA and cortisol; (iii) androstenedione and estrone; and (iv) 11-deoxycortisol and cortisol. Testosterone appears to increase acutely and independently of other intermediary hormones after resistance exercise. In conclusion, lower-concentration intermediary gonadosteroids (e.g. estrone) and corticosteroids (e.g. corticosterone) respond robustly to resistance exercise in strength-trained men, although it seems that testosterone concentrations are regulated by factors other than the availability of precursor hormones and changes in plasma volume.

Kleeb Bua Daeng, a Thai Traditional Herbal Formula, Ameliorated Unpredictable Chronic Mild Stress-Induced Cognitive Impairment in ICR Mice.

Thai traditional herbal formula ''Kleeb Bua Daeng (KBD)''consists of a 1:1:1 ratio (dry weight) of three medicinal plants: Piper nigrum fruit, the aerial part of Centella asiatica and the petals of Nelumbo nucifera. Oral administration of KBD to unpredictable chronic mild stress (UCMS) mice significantly improved their cognitive function caused by chronic mild stress. Daily administration of KBD significantly decreased the serum corticosterone (CORT) and malondialdehyde (MDA) levels but increased the catalase and superoxide dismutase activities in both frontal cortex and hippocampus. The effects of KBD were similar to those caused by oral administration of vitamin E. HPLC analysis of the KBD extract revealed the presence of piperine, madecassoside, asiaticoside, luteolin-7-O-glucoside, rutin, kaempferol-3-glucoside, quercetin, kaempferol and ferulic acid as major constituents.

A cross-sectional survey of adrenal steroid hormones among overweight/obese boys according to puberty stage.

BACKGROUND: Obesity is associated with many chronic diseases including cortisol rhythm disorder and low testosterone. Furthermore, studies on obese children are quite limited and no concordance results have been obtained, especially for boys in puberty. Moreover, the sample sizes of previous studies were small, and were not representative. METHODS: We conducted a cross-sectional survey including 1148 boys aged 6-14 years, they were divided into overweight/obesity (OW/OB) group and normal weight (NW) group. Puberty status was assessed according to Tanner scale and testicular volume. Serum levels of pregnenolone, 17-OH progesterone, corticosterone, dehydroepiandrosterone (DHEA), and androstenedione were detected by LC-MS. Serum free testosterone and sex hormone-binding globulin (SHBG) levels were measured by chemiluminescence immunoassay. RESULTS: The 17-OH progesterone, DHEA, androstenedione and free testosterone levels of OW/OB boys at prepubertal stage or at the age 6 = < 10 years group were higher than those of the NW boys (all the P values were < 0.01). Furthermore, androstenedione and free testosterone levels were lower in OW/OB boys at late puberty, and the trend continued at the post pubertal stage for FT (P < 0.01-0.05). DHEA, androstenedione, and FT levels persisted to be higher at the 10~ < 12 years in OW/OB boys but not for 17-OH progesterone. FT level was lower in the OW/OB group at the 12~ < 15 years group. The SHBG levels in the OW/OB boys were lower than those in the NW ones at the 6~12 years group, and prepubertal to early pubertal stage. CONCLUSIONS: Premature adrenarche is more likely in OW/OB boys. More attention should be given to the lower androgen levels of OW/OB boys at late pubertal and post pubertal stages.

Oral dosing for antenatal corticosteroids in the Rhesus macaque.

Antenatal corticosteroids (ACS) are standard of care for women at risk of preterm delivery, although choice of drug, dose or route have not been systematically evaluated. Further, ACS are infrequently used in low resource environments where most of the mortality from prematurity occurs. We report proof of principle experiments to test betamethasone-phosphate (Beta-P) or dexamethasone-phosphate (Dex-P) given orally in comparison to the clinical treatment with the intramuscular combination drug beta-phosphate plus beta-acetate in a Rhesus Macaque model. First, we performed pharmacokinetic studies in non-pregnant monkeys to compare blood levels of the steroids using oral dosing with Beta-P, Dex-P and an effective maternal intramuscular dose of the beta-acetate component of the clinical treatment. We then evaluated maternal and fetal blood steroid levels with limited fetal sampling under ultrasound guidance in pregnant macaques. We found that oral Beta is more slowly cleared from plasma than oral Dex. The blood levels of both drugs were lower in maternal plasma of pregnant than in non-pregnant macaques. Using the pharmacokinetic data, we treated groups of 6-8 pregnant monkeys with oral Beta-P, oral Dex-P, or the maternal intramuscular clinical treatment and saline controls and measured pressure-volume curves to assess corticosteroid effects on lung maturation at 5d. Oral Beta-P improved the pressure-volume curves similarly to the clinical treatment. Oral Dex-P gave more variable and nonsignificant responses. We then compared gene expression in the fetal lung, liver and hippocampus between oral Beta-P and the clinical treatment by RNA-sequencing. The transcriptomes were largely similar with small gene expression differences in the lung and liver, and no differences in the hippocampus between the groups. As proof of principle, ACS therapy can be effective using inexpensive and widely available oral drugs. Clinical dosing strategies must carefully consider the pharmacokinetics of oral Beta-P or Dex-P to minimize fetal exposure while achieving the desired treatment responses.