Plasma Steroid Research Articles

Cell-Associated Human Immunodeficiency Virus (HIV) Ribonucleic Acid Has a Circadian Cycle in Males With HIV on Antiretroviral Therapy.

Circadian transcription factors that regulate cell-autonomous circadian clocks can also increase human immunodeficiency virus (HIV) transcription in vitro. We aimed to determine whether circadian variation in HIV transcription exists in people with HIV (PWH) on antiretroviral therapy (ART). We performed a prospective observational study of male PWH on ART, sampling blood every 4 hours for 24 hours. Using quantitative polymerase chain reaction, we quantified expression of circadian-associated genes, HIV deoxyribonucleic acid (DNA), and cell-associated unspliced (CA-US) ribonucleic acid (RNA) in peripheral blood CD4+ T cells. Plasma sex hormones were quantified alongside plasma and salivary cortisol. The primary outcome was to identify temporal variations in CA-US HIV RNA using a linear mixed-effect regression framework and maximum likelihood estimation. Salivary and plasma cortisol, and circadian genes including Clock, Bmal1, and Per3, varied with a circadian rhythm. Cell-associated unspliced HIV RNA and the ratio of CA-US HIV RNA/DNA in CD4+ T cells also demonstrated circadian variations, with no variation in HIV DNA. Circulating estradiol was highly predictive of CA-US HIV RNA variation in vivo. Cell-associated unspliced HIV RNA in PWH on ART varies temporally with a circadian rhythm. These findings have implications for the design of clinical trials and biomarkers to assess HIV cure interventions.

PSIII-15 The interactions of change in nutrition after artificial insemination on plasma metabolites, steroid hormones, and uterine histotroph in beef heifers

Abstract The objective was to evaluate the impact of nutritional changes after artificial insemination (AI) on plasma metabolites, steroid hormones, and uterine histotroph. Beef heifers (n = 50) were randomly assigned to a post-AI dietary treatment (High=161.5% or Low=77.45% of maintenance energy) until uteri were flushed for embryo recovery (d14). Blood samples were collected on d -3, 0 (AI), 3, 6, 9, 12, and 14 for analysis of plasma non-esterified fatty acid (NEFA), total protein (protein), glucose, cholesterol, and progesterone concentrations. Uterine flushes (UF) were analyzed for concentrations of Mg, P, S, K, Ca, Cu, Zn, Se, Mn, Co, B, Cr, and Fe. Plasma NEFA, protein, glucose, cholesterol, and progesterone concentrations were analyzed as repeated measures in SAS (PROC MIXED). Mineral concentrations in UF were analyzed using the MIXED procedures in SAS. Diet influenced plasma NEFA concentrations, with Low heifers having elevated concentrations (P < 0.01); however, diet did not influence plasma protein, glucose, cholesterol, or progesterone concentrations (P > 0.10). Plasma NEFA, glucose, and progesterone concentrations changed over time (P < 0.05), but protein and cholesterol did not differ over time (P > 0.10). Diet by time interactions influenced plasma NEFA, protein, and cholesterol concentrations (P < 0.05), but glucose and progesterone concentrations were not different (P > 0.10). Presence of a recovered embryo by time interaction influenced plasma protein concentrations (P < 0.04), but NEFA, glucose, cholesterol, and progesterone concentrations were not affected by the interaction (P > 0.10). Embryo recovery and diet by embryo recovery by time did not impact plasma NEFA, protein, glucose, cholesterol and progesterone concentrations (P > 0.10). When an embryo was recovered, Mg (P = 0.02) and S (P = 0.02) were decreased in UF. Diet and diet by embryo recovery did not affect UF mineral concentrations (P>0.10). In conclusion, post-AI nutrition influenced plasma NEFA, protein, glucose, cholesterol, and progesterone concentrations. Additionally, uterine histotroph mineral concentrations were affected by presence of an embryo.

Adrenal steroids reference ranges in infancy determined by LC-MS/MS

Interpretation of the results of steroid hormone measurements is challenging at early infancy. The liquid chromatography-tandem mass spectrometry (LC-MS/MS) method provides a powerful tool for diagnosing steroidogenesis disorders. We aimed to develop normative data for a 14-steroid panel and four adrenal enzyme activity indices, determined by LC-MS/MS from 3 days to 6 months of age. Age- and sex-specific plasma steroid concentrations were calculated in 324 healthy full-term neonates and infants (151 females). Percentile curves were devised. Steroid ratios were evaluated as biomarkers of adrenal enzyme activities. The steroid profiles of four patients with adrenal enzyme deficiencies were included to test the diagnostic efficiency. Nine steroids showed age, but none showed sex specificity. The concentrations of progestins and androgens were higher at 7-14 days than at 3-7 days. After the first month, adrenal androgen concentrations decreased significantly. Adrenal enzyme activities changed towards increasing cortisol over the first 6 months. There were several-fold differences in diagnostic steroids and related adrenal enzyme activity indices between the patients and the healthy group. The majority of adrenal steroids show age-related variations in the neonatal period and early infancy. Our data will enable accurate interpretation of steroid measurements for etiologic diagnosis of disorders of steroidogenesis. LC-MS/MS method is capable of quantitating numerous analytes simultaneously, which provides an integrated picture of adrenal steroidogenesis in a small amount of sample. The development of LC-MS/MS-based normative data of steroid hormones in healthy infants is crucial to differentiate physiologic alterations from steroidogenic defects during the first 3-6 months of infancy. Previous studies had limitations due to the small numbers of samples available by sex and by age groups. Our detailed normative data and percentile curves will enable accurate interpretation of steroid measurements for etiologic diagnosis of disorders of steroidogenesis without the need for further invasive testing.

Plasma steroid profiling in patients with adrenal incidentaloma

Plasma steroid profiling in patients with adrenal incidentaloma

Development of a polymerase chain reaction (PCR)-based genetic sex identification method in the chub mackerel Scomber japonicus and blue mackerel S. australasicus

Chub mackerel Scomber japonicus and blue mackerel S. australasicus have become important aquaculture target species in Japan. For an efficient and stable aquaculture production of mackerels, it is desirable to work with a female-biased broodstock and thus to be able to manage precisely their sex ratio. As these two mackerel species do not have any external sexual dimorphism, direct biopsy of the gonads or measurement of sex hormone plasma levels is used in research to determine their phenotypic sex. However, these methods are associated with handling stress that results in gonadal atresia. Besides, it is difficult to identify sex using these methods in immature individuals. Therefore, genetic sexing would be desirable in these species to overcome these problems. In this study, we developed molecular sex identification tools for both chub and blue mackerels using sex-specific single-nucleotide variations (SNVs) identified by pool-sequencing (pool-seq) analyses. Genomic DNA was isolated from 30 males and females, in each species, and sequenced as pooled samples. Results of these pool-seq analyses identified a clear XX/XY male heterogametic sex-determination system in blue mackerel and a ZZ/ZW female heterogametic system in chub mackerel. Using this pool-seq information, we designed primer sets for genetic sex identification in both species. Results demonstrated that these primer sets are robust and accurate in assessing the genotypic sex of both blue and chub mackerels (accuracy > 99.5% in the chub, and > 94.5% in the blue mackerel) in various geographical samples of different ages. This method can now be applied for the efficient management of sex ratios in both mackerel aquaculture populations and wild-caught animals for fisheries management.

Catch-up Growth and Discontinuation of Fludrocortisone Treatment in Aldosterone Synthase Deficiency.

Aldosterone synthase deficiency (ASD) caused by mutations in the CYP11B2 gene is characterized by isolated mineralocorticoid deficiency. Data are scarce regarding clinical and biochemical outcomes of the disease in the follow-up. Assessment of the growth and steroid profiles of patients with ASD at the time of diagnosis and after discontinuation of treatment. Children with clinical diagnosis of ASD were included in a multicenter study. Growth and treatment characteristics were recorded. Plasma adrenal steroids were measured using liquid chromatography-mass spectrometry. Genetic diagnosis was confirmed by CYP11B2 gene sequencing and in silico analyses. Sixteen patients from 12 families were included (8 females; median age at presentation: 3.1 months, range: 0.4 to 8.1). The most common symptom was poor weight gain (56.3%). Median age of onset of fludrocortisone treatment was 3.6 months (range: 0.9 to 8.3). Catch-up growth was achieved at median 2 months (range: 0.5 to 14.5) after treatment. Fludrocortisone could be stopped in 5 patients at a median age of 6.0 years (range: 2.2 to 7.6). Plasma steroid profiles revealed reduced aldosterone synthase activity both at diagnosis and after discontinuation of treatment compared to age-matched controls. We identified 6 novel (p.Y195H, c.1200 + 1G > A, p.F130L, p.E198del, c.1122-18G > A, p.I339_E343del) and 4 previously described CYP11B2 variants. The most common variant (40%) was p.T185I. Fludrocortisone treatment is associated with a rapid catch-up growth and control of electrolyte imbalances in ASD. Decreased mineralocorticoid requirement over time can be explained by the development of physiological adaptation mechanisms rather than improved aldosterone synthase activity. As complete biochemical remission cannot be achieved, a long-term surveillance of these patients is required.

Hemolytic uremic syndrome complicated with IgA nephropathy: a clinicopathological study

Objective: To investigate the clinicopathologic characteristics, treatments, outcomes and mechanisms of hemolytic uremic syndrome (HUS) complicated with IgA nephropathy (IgAN). Methods: The clinical manifestations, treatments, prognosis and histopathological features of renal biopsy tissues were analyzed in two cases of HUS complicated with IgAN from Beijing Children's Hospital, Capital Medical University using light microscopy, immunofluorescence detection and electron microscopy. The related literatures were also reviewed. Results: The clinical manifestations were microvascular hemolytic anemia, thrombocytopenia, acute renal impairment with hematuria, proteinuria, and positive anti-H factor antibody. Histological findings confirmed presence of both HUS and IgAN. Histological features included glomerular mesangial and stromal hyperplasia with endothelial cell proliferation, capillary stenosis, arteriolar thickening, and glomerular ischemia and capillary dilatation. Immunofluorescence detection showed diffuse IgA deposition in the glomerular mesangial matrix. Electron microscopy showed proliferation of mesangial and endothelial cells, thickening of the inner layer of the glomerular basement membrane, deposition of massive electronic densification in the mesangial region, and shrinkage of the segmental basement membrane. The two children were very responsive to plasma exchange and steroid treatments. However, their urine protein and occult blood tests remained continuously positive during the follow-up of 5 years 7 months and 8 months respectively. Conclusions: HUS complicated with IgAN is rare. The diagnosis relies on various pathological examinations, which require the combination of light microscopy, immunofluorescence detection and electron microscopy. Plasma exchange and steroid treatments are effective. However, the long-term prognosis is concerning and may relate to pathological grade and secondary factors. The mechanism of connecting HUS and IgAN is unknown, but may be caused by prodromal or secondary factors.

Sudden coma at the onset of severe refractory thrombotic thrombocytopenic purpura with successful treatment

Most patients develop coma several days after the onset of thrombotic thrombocytopenic purpura (TTP) caused by microvascular occlusion. However, aggravated coma as the first symptom of TTP has rarely been reported. Although plasma exchange (PEX) and steroids have reduced mortality, the prognosis of patients with TTP is still poor. We reported a patient with refractory TTP presenting with aggravated coma on admission. After days of successful PEX, rituximab, and glucocorticoid therapy for clinical remission, the patient regained consciousness and returned to his normal life with a good outcome. Our case highlights that TTP should be considered when coma occurs as the first symptom.

Exogenous oxytocin administration improves the testicular blood flow in rams.

The current research aimed to examine the effects of single-dose oxytocin administration on testicular blood flow measurements peak systolic velocity (PSV), end-diastolic velocity (EDV), resistive index (RI) and pulsatility index (PI) and plasma steroid (testosterone and oestradiol-17β) concentrations in rams. In the treated group, eight mature Ossimi rams during the breeding season were injected intravenously (iv)with 20IU oxytocin, while the othereight male rams were administered normal saline (2ml) ivas a control group. Venous blood samples and testicular blood flow in the left and right testes were examined immediately before (0) and 5, 30, 60 and 120min after injections. The control group did not show significant changes in the variables examined (p>.05), except for the EDV (p<.05). In the treated group, the administration of oxytocin led to a significant decrease in RI and PI values starting 5min after oxytocin administration until 60min after its application (p<.05). The plasma concentrations of testosterone and oestradiol-17β raised from 5 to30min after oxytocin injection (p>.05) and then declined significantly until 120min (p<.05). In conclusion, oxytocin is a potent testicular vasodilator affecting the testicular vascular tone and steroid concentrations in rams.

Classic and Novel Sex Hormone Binding Globulin Effects on the Cardiovascular System in Men.

In men, 70% of circulating testosterone binds with high affinity to plasma sex hormone binding globulin (SHBG), which determines its bioavailability in their target cells. In recent years, a growing body of evidence has shown that circulating SHBG not only is a passive carrier for steroid hormones but also actively regulates testosterone signaling through putative plasma membrane receptors and by local expression of androgen-binding proteins apparently to reach local elevated testosterone concentrations in specific androgen target tissues. Circulating SHBG levels are influenced by metabolic and hormonal factors, and they are reduced in obesity and insulin resistance, suggesting that SHBG may have a broader clinical utility in assessing the risk for cardiovascular diseases. Importantly, plasma SHBG levels are strongly correlated with testosterone concentrations, and in men, low testosterone levels are associated with an adverse cardiometabolic profile. Although obesity and insulin resistance are associated with an increased incidence of cardiovascular disease, whether they lead to abnormal expression of circulating SHBG or its interaction with androgen signaling remains to be elucidated. SHBG is produced mainly in the liver, but it can also be expressed in several tissues including the brain, fat tissue, and myocardium. Expression of SHBG is controlled by peroxisome proliferator-activated receptor γ (PPARγ) and AMP-activated protein kinase (AMPK). AMPK/PPAR interaction is critical to regulate hepatocyte nuclear factor-4 (HNF4), a prerequisite for SHBG upregulation. In cardiomyocytes, testosterone activates AMPK and PPARs. Therefore, the description of local expression of cardiac SHBG and its circulating levels may shed new light to explain physiological and adverse cardiometabolic roles of androgens in different tissues. According to emerging clinical evidence, here, we will discuss the potential mechanisms with cardioprotective effects and SHBG levels to be used as an early metabolic and cardiovascular biomarker in men.

Сезонные особенности функциональной активности эндокринных систем у жителей гор

The article presents the results of studies of changes in the functional state of the endocrine systems of high-altitude residents, depending on the periods of the year that are associated with the ambient temperature, with the daylight regime and other factors. High altitude regions are distinguished by a severely continental climate, which is characterized by large temperature and barometric differences between the winter and summer months, expressed by the seasons of the year. The object of research was the indigenous people of the mountains, living at an altitude of 2800 m above sea level, from 18–55 years old. The level of thyroid hormones, TSH, cortisol, catecholamines and sex hormones in peripheral blood plasma was determined by the method of enzyme-linked immunosorbent assay using standard test kits (Russia). It was found that in high-altitude conditions there is a seasonal variability in the functional activity of the pituitary-thyroid system in healthy men leads to an increase in metabolism, since rhythmic changes in the secretion of thyroid hormones and biochemical parameters are interrelated. So, in winter, the level of triiodothyronine is increased with a slight change towards a decrease in thyroxine and thyroid-stimulating hormone of the adenohypophysis compared with the summer months. At the same time, the above studies did not reveal a clear relationship between the functional state of the thyroid gland and atmospheric pressure and ambient temperature. Norepinephrine and dopamine levels rise significantly in winter, with a slight decrease in other neurotransmitters, adrenaline and serotonin. In the studied mountainous region in winter, the ambient temperature is significantly lower than in summer, and has an additional effect on the functional state of the endocrine systems after hypoxia. Compensatory-adaptive changes when exposed to low temperature of the environment are triggered with the participation of catecholamines, which, by breaking down fats and carbohydrates, mobilize energy reserves, increase heat production and constrict the vessels of the body surface. Interacting with catecholamines, thyroid hormones activate metabolic processes, also increase heat generation, affecting the processes of oxidative phosphorylation, enhance the “calorigenic” effect of catecholamines, and also activate the secretion of ACTH and glucocorticosteroids. Fluctuations in the level of the studied hormones in the peripheral blood in the indigenous population of the highlands are subject to changes not only in the seasons of the year, but also in the duration of daylight hours. To date, there are data (including those obtained experimentally) that show the effect of light on the release of sex hormones and cortisol in humans, which indicate changes in the secretion of these hormones during the year, associated with a change in the length of daylight hours.

Carbon isotope ratios of endogenous steroids found in human serum\u2014method development, validation, and reference population-derived thresholds

In order to detect the misuse of testosterone (T), urinary steroid concentrations and concentration ratios are quantified and monitored in a longitudinal manner to enable the identification of samples exhibiting atypical test results. These suspicious samples are then forwarded to isotope ratio mass spectrometry (IRMS)–based methods for confirmation. Especially concentration ratios like T over epitestosterone (E) or 5α-androstanediol over E proved to be valuable markers. Unfortunately, depending on the UGT2B17 genotype and/or the gender of the athlete, these markers may fail to provide evidence for T administrations when focusing exclusively on urine samples. In recent years, the potential of plasma steroids has been investigated and were found to be suitable to detect T administrations especially in female volunteers. A current drawback of this approach is the missing possibility to confirm that elevated steroid concentrations are solely derived from an administration of T and cannot be attributed to confounding factors. Therefore, an IRMS method for plasma steroids was developed and validated taking into account the comparably limited sample volume. As endogenous reference compounds, unconjugated cholesterol and dehydroepiandrosterone sulfate were found suitable, while androsterone and epiandrosterone (both sulfo-conjugated) were chosen as target analytes. The developed method is based on multi-dimensional gas chromatography coupled to IRMS in order to optimize the overall assay sensitivity. The approach was validated, and a reference population encompassing n = 65 males and females was investigated to calculate population-based thresholds. As proof-of-concept, samples from volunteers receiving T replacement therapies and excretion study samples were investigated.Graphical abstract

Melatonin Alleviated Potassium Dichromate-Induced Oxidative Stress and Reprotoxicity in Male Rats.

Melatonin (ML) is a potent antioxidant that reduces oxidative stress. This study was designed to examine the protective effect of melatonin on potassium dichromate- (PDC-) induced male reproductive toxicity. Forty rats were divided into five groups: the control group, rats administered PDC orally (10 mg/kg body weight) for eight weeks, rats administered ML intraperitoneally at doses of either 2.5 or 5 mg/kg followed by the administration of PDC, and rats administered 5 mg/kg ML only. The treatment of rats with PDC led to a decrease in the levels of plasma sex hormones, glutathione, superoxide dismutase, catalase, carnitine, sperm count, and motility. Testicular malondialdehyde levels, nitric oxide concentrations, and abnormalities increased significantly in the PDC group. Melatonin administration to the PDC-treated rats reduced the increase of malondialdehyde and restored the activity of antioxidant enzymes (superoxide dismutase and catalase), glutathione, and sex hormone levels. Moreover, ML attenuated PDC-induced increase in levels of tumor necrosis factor-alpha or interleukin-6. ML alleviated histopathological changes and an increase of p53-positive immune reaction due to PDC. Furthermore, ML inhibited PDC-induced decrease in the DNA content of spermatogenic cells. This study proposed that melatonin may be useful in mitigating oxidative stress-induced testicular damage due to potassium dichromate toxicity.

Effects of buserelin administration on testicular blood flow and plasma concentrations of testosterone and estradiol-17β in rams

This research aimed to examine for the first time the impact of single dose administration of gonadotropin-releasing hormone (GnRH) analog buserelin acetate on the testicular blood flow measurements (peak systolic velocity [PSV], end-diastolic systolic velocity [EDV], resistive index [RI], and pulsatility index [PI]) and the plasma steroids (testosterone and estradiol-17β) concentrations in rams. For this purpose, twelve adult Ossimi rams were randomly assigned into the buserelin group (n = 8) and were injected intravenously (iv) with buserelin acetate (0.008 mg/ram), whereas the remaining rams (n = 4) were injected with normal saline iv and served as a control group. Blood sampling and testicular pulsed-wave Doppler scanning were conducted immediately before (0) and 1, 3, 6, 24, 48, 72, 120, and 168 h after treatment. The control group did not reveal any substantial changes (P > 0.05) in the examined parameters, except for the EDV (P < 0.05). In the buserelin-treated group, a marked reduction in RI and PI values (P < 0.05) occurred 1 to 3 h after administration of buserelin. Besides, there was a significant increase in testosterone plasma concentrations following buserelin treatment. In conclusion, the administration of buserelin triggered a series of substantial changes in the testicular blood perfusion and steroidogenesis that could have a positive effect on testicular function in rams.

Perinatal exposure to known endocrine disrupters alters ovarian development and systemic steroid hormone profile in rats

Disrupted ovarian development induced by chemical exposure may impair fertility later in life. Since androgens are essential for early ovarian development, we speculated that perinatal exposure to a binary mixture of the known anti-androgens DEHP and procymidone could alter steroid synthesis, disrupt ovarian follicle recruitment and ultimately maturation in female rat offspring. Wistar rat dams were exposed by oral gavage from gestation day 7 to postnatatal day 22 to two mixture doses known to alter reproductive development in male offspring (low: 10 mg/kg bw/day of procymidone and 30 mg/kg bw/day of DEHP; high: 20 mg/kg bw/day of procymidone and 60 mg/kg bw/day of DEHP). The Effects on plasma steroid hormones, ovarian follicle distribution and expression of markers related to steroid synthesis were examined in female offspring. In prepubertal offspring, we observed an increased number of newly recruited (primary) follicles in exposed animals compared to controls, and the plasma steroid hormone profile was altered by exposure: levels of progesterone, corticosterone and estrone were dose dependently elevated, whereas androgen levels were unaffected. In adulthood, a trend towards a smaller number of early-stage follicles may point to accelerated loss of follicle reserves, which is disconcerting. The changes in follicle distribution in exposed ovaries may reflect the combined influence of androgen receptor antagonism and altered ovarian steroid synthesis. This study adds to a growing body of evidence showing altered ovarian development following exposure to human relevant chemicals with possible severe consequences for female fertility.

Gonadal steroid hormone receptors in the medial amygdala contribute to experience-dependent changes in stress vulnerability

Social experience can generate neural plasticity that changes how individuals respond to stress. Winning aggressive encounters alters how animals respond to future challenges and leads to increased plasma testosterone concentrations and androgen receptor (AR) expression in the social behavior neural network. In this project, our aim was to identify neuroendocrine mechanisms that account for changes in stress-related behavior following the establishment of dominance relationships over a two-week period. We used a Syrian hamster model in which acute social defeat stress increases anxiety-like responses in a conditioned defeat test in males and in a social avoidance test in females. First, we administered flutamide, an AR antagonist, via intraperitoneal injections daily during the establishment of dominance relationships in male hamsters. We found that pharmacological blockade of AR prevented a reduction in conditioned defeat in dominant males and blocked an upregulation of AR in the posterior dorsal medial amygdala (MePD) and posterior ventral medial amygdala (MePV), but not in the ventral lateral septum. Next, we administered flutamide into the posterior aspects of the medial amygdala (MeP) prior to acute social defeat stress or prior to conditioned defeat testing in males. We found that pharmacological blockade of AR in the MeP prior to social defeat, but not prior to testing, increased the conditioned defeat response in dominant males and did not alter behavior in subordinates. Finally, we developed a procedure to establish dominance relationships in female hamsters and investigated status-dependent changes in plasma steroid hormone concentrations, estrogen receptor alpha (ERα) immunoreactivity, and defeat-induced social avoidance. We found that dominant female hamsters showed reduced social avoidance regardless of social defeat exposure as well as increased ERα expression in the MePD, but no status-dependent changes in the concentration of plasma steroid hormones. Overall, these findings suggest that achieving and maintaining stable social dominance leads to sex-specific neural plasticity in the MeP that underlies status-dependent changes in stress vulnerability.

The effects of three types of exercise training on steroid hormones in physically inactive middle-aged adults: a randomized controlled trial.

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. A 12-week randomized controlled trial was performed with a parallel-group design. A total of 67 (36 women) middle-aged adults (45-65years 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 150min/week at 60-65% of the heart rate reserve for aerobic training and ~ 60min/week at 40-50% of the one-repetition maximum for resistance training. The training volume in the HIIT and HIIT + EMS groups was 40-65min/week at > 95% of the maximum oxygen uptake in long interval sessions, and > 120% of the maximum oxygen uptake in short interval sessions. 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). 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. NCT03334357 (ClinicalTrials.gov). November 7, 2017 retrospectively registered.

Sex steroid hormones and the associated morphological changes in the reproductive tract of free-living males of the cururu stingray Potamotrygon wallacei

This study analyzed sex steroid hormones and morphology of the reproductive tract in free-living adult males of the cururu stingray (Potamotrygon wallacei). These stingrays were captured during the transition between drought and rising waters in the middle Rio Negro basin, which coincides with the reproductive period (spermatogenesis and copulation) of this endemic species. Levels of the plasma steroid hormones testosterone (T), 17 β-estradiol (E2), and progesterone (P4), the gonadosomatic and hepatosomatic indices, as well as histological characteristics of the testis and epididymis were evaluated. Three reproductive maturational stages were observed: regression males, capable to reproduce males, and active males. Plasma T levels were increasing and parallel with the rising water period in the middle Rio Negro basin and were associated with the progress of spermatogenesis. This was not observed for E2, which did not vary significantly among the different reproductive stages. The high P4 concentrations in males in regression and males capable of reproducing appeared to regulate the progression of spermatogenesis. Increases in this hormone in the plasma of active males was associated with spermiogenesis and spermiation events. These findings have not been previously observed in Amazonian freshwater stingrays and demonstrate that the reproductive activity of P. wallacei males is concomitant to the period of rising waters in the middle Rio Negro basin, and is regulated by the action of gonadal steroids, mainly testosterone.

Clinical and Hormonal Profiles Correlate With Molecular Characteristics in Patients With 11β-Hydroxylase Deficiency

Given the rarity of 11β-hydroxylase deficiency (11βOHD), there is a paucity of data about the differences in clinical and biochemical characteristics of classic (C-11βOHD) and nonclassic 11βOHD (NC-11βOHD). To characterize a multicenter pediatric cohort with 11βOHD. The clinical and biochemical characteristics were retrospectively retrieved. CYP11B1 gene sequencing was performed. Seventeen plasma steroids were quantified by liquid chromatography-mass spectrometry and compared to that of controls. 102 patients (C-11βOHD, n = 92; NC-11βOHD, n = 10) from 76 families (46,XX; n = 53) had biallelic CYP11B1 mutations (novel 9 out of 30). Five 46,XX patients (10%) were raised as males. Nineteen patients (19%) had initially been misdiagnosed with 21-hydroxylase deficiency. Female adult height was 152 cm [-1.85 SD score (SDS)] and male 160.4 cm (-2.56 SDS).None of the NC-11βOHD girls had ambiguous genitalia (C-11βOHD 100%), and none of the NC-11βOHD patients were hypertensive (C-11βOHD 50%). Compared to NC-11βOHD, C-11βOHD patients were diagnosed earlier (1.33 vs 6.9 years; P < 0.0001), had higher bone age-to-chronological age (P = 0.04) and lower adult height (-2.46 vs -1.32 SDS; P = 0.05). The concentrations of 11-oxygenated androgens and 21-deoxycortisol were low in all patients. The baseline ACTH and stimulated cortisol were normal in NC-11βOHD. Baseline cortisol; cortisone; 11-deoxycortisol; 11-deoxycorticosterone and corticosterone concentrations; and 11-deoxycortisol/cortisol, 11-deoxycorticosterone/cortisol, and androstenedione/cortisol ratios were higher in C-11βOHD than NC-11βOHD patients (P < 0.05). The 11-deoxycortisol/cortisol ratio >2.2, <1.5, and <0.1 had 100% specificity to segregate C-11βOHD, NC-11βOHD, and control groups. NC-11βOHD can escape from clinical attention due to relatively mild clinical presentation. However, steroid profiles enable the diagnosis, differential diagnosis, and subtyping of 11βOHD.

POS-695 INTESTINAL OBSTRUCTION COMPLICATING CAMPYLOBATER COLI ENTERITIS IN RENAL TRASNPLANTATION PATIENT

A 30 year old male, with cadaveric renal transplantation 2 years ago , his primary disease was anti-GBM disease diagnosed one year prior to transplantation and treated with 14 sessions of plasma exchange, steroids and cyclophosphamide shortly after that he was initiated on hemodialysis followed by renal transplantation. Two months post renal transplantation his course was complicated by biopsy proven mixed rejection (T-Cell mediated rejection type IA) and active Antibody medicated rejection , however ,C4d negative. The patient received pulsed steroids, 3 sessions Plasma-exchange and IVIG 2g/kg. He completed 2 doses of Rituximab and his serum creatinine was stable at 200-220 micromole/L. The patient was admitted after 3 weeks with persistent vomiting and abdominal pain and abdominal distention, his serum creatinine 304 micromole/L, abdominal x-ray showed multiple air fluid levels with dilatation of small bowel loops. CT scan with oral contrast showed multiple dilated small bowel loops down to the terminal ileum with caliber of 3.5 mm with multiple air-fluid levels and fecal loading in distal ileum loop with collapsed colon. The contrast media reached into the small bowel in left mid abdomen at mid jejunal loop. Stool culture grew campylobacter coli, BK PCR was positive of 371,000 copies. Other infectious causes of diarrhea were excluded. The patient completed 7 days of ciprofloxacin and treated with intravenous immunoglobulins (IVIG) . His mycophenolic acid was stopped, and he was maintained on dual immunosuppression therapy in form of tacrolimus and steroids. The patient was booked for upper endoscopy and colonoscopy in outpatient setting. View Large Image Figure ViewerDownload Hi-res image Download (PPT) Diarrhea is a common symptom in renal transplant patient population. The main causes of diarrhea after transplantation include infections, immunosuppressive drugs, antibiotics, and other drugs. Viral causes of diarrhea are the most frequently reported and usually last up to 3 days. Patients have tendency to develop Clostridium difficile after antibiotics. Other enteric bacteria responsible for diarrhea are Shigella, Salmonella typhi, Salmonella typhimurium and Campylobacter. CMV can cause enterocolitis, with or without fever, gastrointestinal bleeding, perforation, and toxic megacolon are possible complications. Incidence of diarrhea with mycophenolate mofetil dose of 2 g/day was higher than in other immunosuppressants like azathioprine. Campylobacter infection has prominent features like terminal ileitis, cecitis and mesenteric adenitis. Proton pump inhibitors are main risk factor for campylobacter enteritis as it lowers the gastric juice acidity allowing for pathogen survival. Campylobacter was detected in stool culture of a 31-year-old male patient diagnosed with immunoproliferative small intestinal disease (IPSID) and it was positive in tissue biopsy samples. Antibiotics treatment is enough to eradicate campylobacter and reduce the risk of IPSID. Diarrhea is a common symptom post renal transplantation, Campylobacter coli can be one of the main causes of ileocecal enteritis and may cause small bowel obstruction, treatment is usually conservative with antibiotics.