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Sample records for dehydroepiandrosterone sulfate dhea-s

  1. Dehydroepiandrosterone sulfate (DHEA-S) and Alzheimer's dementia in older subjects.

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    Bo, Mario; Massaia, Massimiliano; Zannella, Patrizia; Cappa, Giorgetta; Ferrario, Ermanno; Rainero, Innocenzo; Arvat, Emanuela; Giordano, Roberta; Molaschi, Mario

    2006-11-01

    We investigated the association of serum dehydroepiandrosterone sulfate (DHEA-S) levels with dementia of Alzheimer's type (DAT) and impairment in selected cognitive domains (memory, language, attention and working memory) in 158 patients (75.5+/-6.7 years, 46 men) with first-diagnosed probable DAT and in 158 age- and sex-matched controls. As secondary goal, we evaluated whether DHEA-S baseline levels were associated with cumulative 6-year mortality. A negative correlation between DHEA-S levels and age was observed (R=-0.25, pDHEA-S levels between DAT patients and controls. No significant association was found between DHEA-S levels and impairment in selected cognitive domains. Cox regression analysis showed that baseline DHEA-S levels were not associated with cumulative 6-year mortality. In a sample of newly-diagnosed DAT patients, we did not find significant association between presence of DAT or impairment in cognitive domains and DHEA-S levels; baseline DHEA-S levels are not associated with cumulative mortality in patients and controls. Copyright (c) 2006 John Wiley & Sons, Ltd.

  2. Dehydroepiandrosterone-sulfate (DHEA-S), sex, and age in zoo-housed western lowland gorillas (Gorilla gorilla gorilla).

    Science.gov (United States)

    Edes, Ashley N

    2017-07-01

    Among humans, dehydroepiandrosterone-sulfate (DHEA-S) declines with age and is hypothesized to be involved in somatic maintenance and healthy aging. Men have significantly higher DHEA-S than women, contradicting longer lifespans in the latter. Declines of DHEA-S with age also are observed in chimpanzees. In both chimpanzees and bonobos, males and females show no differences in DHEA-S production. Based on human and chimpanzee data, gorillas were predicted to show declining DHEA-S with age. Similar to chimpanzees and bonobos, it also was predicted DHEA-S would not be significantly different between males and females. DHEA-S was assayed from serum banked during physical examinations of gorillas housed at three North American zoos (n = 63). Gorillas ranged from 6 to 52 years of age. Differences between males and females were examined using t tests. Linear regression was used to determine the relationship of DHEA-S with age. There was no significant difference in DHEA-S between males and females. Additionally, there was no significant relationship between DHEA-S and age. As predicted, there were no sex-based differences in DHEA-S in gorillas, which is similar to chimpanzees and bonobos but different from modern humans. Unlike chimpanzees and humans, there was no significant relationship between DHEA-S and age in gorillas. The absence of a relationship between age and DHEA-S may be due to the lack of gorillas under age 6 years in this sample as declines in chimpanzees occur prior to age 5 years, more rapid growth and development among gorillas compared with other African hominoids, or a unique pattern of DHEA-S production.

  3. [Dehydroepiandrosterone [DHEA(S)]: anabolic hormone?].

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    Luci, Michele; Valenti, Giorgio; Maggio, Marcello

    2010-09-01

    The role of dehydroepiandrosterone (DHEA) and its sulphated form (DHEAS) as anabolic hormones is still debated in the literature. In this review we describe the fundamental steps of DHEA physiological secretion and its peripheral metabolism. Moreover we will list all the observational and intervention studies conducted in humans. Many observational studies have tested the relationship between low DHEA levels and age-related changes in skeletal muscle and bone, while intervention studies underline the positive and significant effects of DHEA treatment on several parameters of body composition. Surprisingly, observational studies are not consistent with different effects in men and women. There is recent evidence of a significant role of DHEA in frailty syndrome and as predictor of mortality. However a more complete approach of the problem suggests the opportunity to not focus only on one single hormonal derangement but to analyze the parallel dysregulation of anabolic hormones including sex steroids, GH-IGF-1 system and other catabolic hormones.

  4. Dehydroepiandrosterone, Its Sulfate and Cognitive Functions

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    de Menezes, Karina Junqueira; Peixoto, Clayton; Nardi, Antonio Egidio; Carta, Mauro Giovanni; Machado, Sérgio; Veras, André Barciela

    2016-01-01

    To present a review of cross-sectional and longitudinal studies that investigate the relationship between the hormones Dehydroepiandrosterone (DHEA) and Dehydroepiandrosterone sulfate (DHEA-S) and cognition. Methods: The cognition items included in this review were global cognitive function, memory, attention, executive function, intelligence, perception and visuospatial ability. A systematic review was proceeded using three databases: PubMed, ISI Web of Science, and PsycINFO. Results: Two thousand fifty five references about cognition and hormones were found; 772 duplicated references were excluded, resulting in 1.283 references to be evaluated. According to exclusion and inclusion criteria, 25 references were selected. A positive correlation between DHEA-S blood levels and global cognition was found in women and men. Other positive correlations between DHEA-S and working memory, attention and verbal fluency were found only in women. The DHEA effect on cognition is limited to one study conducted among young men with high-doses. PMID:27346998

  5. Dehydroepiandrosterone, Its Sulfate and Cognitive Functions.

    Science.gov (United States)

    de Menezes, Karina Junqueira; Peixoto, Clayton; Nardi, Antonio Egidio; Carta, Mauro Giovanni; Machado, Sérgio; Veras, André Barciela

    2016-01-01

    To present a review of cross-sectional and longitudinal studies that investigate the relationship between the hormones Dehydroepiandrosterone (DHEA) and Dehydroepiandrosterone sulfate (DHEA-S) and cognition. The cognition items included in this review were global cognitive function, memory, attention, executive function, intelligence, perception and visuospatial ability. A systematic review was proceeded using three databases: PubMed, ISI Web of Science, and PsycINFO. Two thousand fifty five references about cognition and hormones were found; 772 duplicated references were excluded, resulting in 1.283 references to be evaluated. According to exclusion and inclusion criteria, 25 references were selected. A positive correlation between DHEA-S blood levels and global cognition was found in women and men. Other positive correlations between DHEA-S and working memory, attention and verbal fluency were found only in women. The DHEA effect on cognition is limited to one study conducted among young men with high-doses.

  6. The Role of Dehydroepiandrosterone Sulfate In Chronic Idiopathic Urticaria Pathogenesis

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    Filiz Canpolat

    2009-03-01

    Full Text Available Objective: Adrenal androgens, dehydroepiandrosterone (DHEA and dehydroepiandrosterone sulfate (DHEA-S seem implicated in the pathophysiology of autoimmune disorders, as natural immunosuppressors. The relationship of chronic idiopathic urticaria (CIU with circulating concentration of DHEA-S has been reported previously. However, this link and underlying mechanisms remain unknown. The aim of this study was to evaluate circulating DHEA-S concentration in larger patients group suffering from CIU.Materials and Methods: Serum concentration of DHEA-S was measured in 65 patients (34 women, 31 men with CIU and compared with 40 age and sex matched, non atopic healthy volunteers. Disease duration and extent of involvement were recorded.Results: The patients with CIU presented significantly decreased values of DHEA-S levels (102.66±28.95 µg/dl with respect to control group (174.22±39.58 µg/dl (p<0.01. No significant correlation was found between DHEA-S concentration and the duration of the disease, disease activity and gender.Conclusion: Our results support the hypothesis that DHEA-S may be a cause for the development of CIU, regardless of their gender. For definitive role of DHEA-S in CIU pathogenesis, further studies are needed.

  7. The association between serum dehydroepiandrosterone Sulphate (DHEA-S) level and bone mineral density in Korean men.

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    Lee, Dain; Kim, Hyeonmok; Ahn, Seong Hee; Lee, Seung Hun; Bae, Sung Jin; Kim, Eun Hee; Kim, Hong-Kyu; Choe, Jae Won; Kim, Beom-Jun; Koh, Jung-Min

    2015-08-01

    Many lines of evidence indicate that dehydroepiandrosterone (DHEA) plays a distinct role in bone metabolism and that its sulphated form (DHEA-S), which is easily measured in blood, may be a potential biomarker of osteoporosis-related phenotypes. However, most previous epidemiologic studies focused on postmenopausal women and reported conflicting results. We aimed to investigate the association between the serum DHEA-S level and bone mass in men. This large cross-sectional study included 1089 healthy Korean men who participated in a routine health screening examination. Bone mineral density (BMD) at the lumbar spine, total femur, femur neck, and trochanter and serum DHEA-S level were obtained in all subjects. After adjustment for age, body mass index, lifestyle factors and serum levels of calcium, phosphorus, testosterone, 25-OH-vitamin D3 and cortisol, higher serum DHEA-S concentrations were associated with higher BMD values at all skeletal sites. Consistently, compared to the subjects in the highest DHEA-S quartile (Q4), those in the lowest DHEA-S quartile (Q1) showed significantly lower BMD values. Multiple logistic regression analyses revealed that the odds ratios for the risk of lower BMD (T-score DHEA-S quartiles and the odds for the risk of lower BMD were 2·59-fold higher in Q1 than in Q4. These findings support previous evidences that DHEA-S has favourable effects on bone mass in men and suggest that a low serum DHEA-S level may be a potential risk factor for male osteoporosis. © 2015 John Wiley & Sons Ltd.

  8. Dehydroepiandrosterone (DHEA) supplementation results in supraphysiologic DHEA-S serum levels and progesterone assay interference that may impact clinical management in IVF.

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    Franasiak, Jason M; Thomas, Semara; Ng, Susan; Fano, Maria; Ruiz, Andrew; Scott, Richard T; Forman, Eric J

    2016-03-01

    Dehydroepiandrosterone (DHEA) is often prescribed for poor responders in IVF in an effort to improve response to ovarian stimulation. The effect of DHEA supplementation and resultant supraphysiologic DHEA-S serum levels on sex steroid assays has not been evaluated in this population. This study seeks to determine the relationship between DHEA supplementation and progesterone measurements to characterize the degree of interference with particular immunoassays. Characterization was accomplished in two phases. First, DHEA-S standard control reagents with no progesterone present were assayed for both DHEA-S and progesterone levels. Second, serum pools from 60 unique IVF patients' serum were used to create six pooled serum samples: three from patients on DHEA supplementation and three from patients not on DHEA supplementation. The three pools were composed of patients whose serum fell into low, medium, and high progesterone ranges. Baseline DHEA-S and progesterone were measured, and the mean level of DHEA-S in the mid-range progesterone pool was used as the mid-point for addition of DHEA-S standard to the serum pools from patients without DHEA supplementation. Progesterone from these pools was then measured on three commercially available immunoassay systems. The first experiment revealed a linear increase in progesterone when analyzing the DHEA-S standard ranging from 0.5 ng/mL in the blank control (no DHEA-S) to up to 2.0 ng/mL in the high control (DHEA-S >700 μg/mL), indicating that the DHEA-S cross-reacts with the progesterone assays. In the second experiment, patients' serum DHEA-S and progesterone were measured from pooled serum samples of those taking DHEA and those not taking DHEA. Adding DHEA-S to the pooled serum of those not taking DHEA resulted in a linear increase in progesterone levels on two of three commercially available immunoassays (p DHEA-S can interfere with standard progesterone immunoassays used in clinical ART programs, and thus serum

  9. DHEA-S selectively impairs contextual-fear conditioning: support for the antiglucocorticoid hypothesis.

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    Fleshner, M; Pugh, C R; Tremblay, D; Rudy, J W

    1997-06-01

    The authors had reported that glucocorticoids play a selective role in fear conditioning. The adrenal steroid dehydroepiandrosterone (DHEA) has been reported to act as a functional antiglucocorticoid. If DHEA has antiglucocorticoid properties, then its effects on fear conditioning might resemble those produced by adrenalectomy. The authors now report that chronic exposure to high levels of dehydroepiandrosterone sulfate (DHEA-S; converted in vivo to DHEA) produced the same pattern of results as adrenalectomy. Specifically, treatment with DHEA-S impaired contextual fear conditioning 24 hr after conditioning but not immediately after conditioning, and like adrenalectomy, DHEA-S had no effect on auditory-cue fear conditioning. Preexposure to the context before drug treatment eliminated the amnestic effects of DHEA-S, suggesting that, like adrenalectomy, DHEA-S exerted its effect by interfering with the construction of a contextual memory representation. Thus, DHEA appears to act as a functional antiglucocorticoid in the processes that mediate learning and memory.

  10. Seasonal and biological variation of blood concentrations of total cholesterol, dehydroepiandrosterone sulfate, hemoglobin A(1c), IgA, prolactin, and free testosterone in healthy women

    DEFF Research Database (Denmark)

    Garde, A H; Hansen, Åse Marie; Skovgaard, L T

    2000-01-01

    Concentrations of physiological response variables fluctuate over time. The present study describes within-day and seasonal fluctuations for total cholesterol, dehydroepiandrosterone sulfate (DHEA-S), hemoglobin A(1c) (HbA(1c)), IgA, prolactin, and free testosterone in blood, and estimates within...

  11. Plasma dehydroepiandrosterone sulfate levels in patients with major depressive disorder correlate with remission during treatment with antidepressants.

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    Morita, Tokiko; Senzaki, Koji; Ishihara, Ryoko; Umeda, Kazunori; Iwata, Nakao; Nagai, Taku; Hida, Hirotake; Nabeshima, Toshitaka; Yukawa, Kazunori; Ozaki, Norio; Noda, Yukihiro

    2014-05-01

    We attempted to investigate whether dehydroepiandrosterone sulfate (DHEA-S) levels are associated with remission of major depressive disorder by assessing scores on the 17-Item Structured Interview Guide for the Hamilton Depression before and after antidepressant treatment. Plasma DHEA-S levels in 24 patients diagnosed with major depressive disorder on the basis of Diagnostic and Statistical Manual of Mental Disorders, fourth edition (text revision) before and after antidepressant treatment, and 24 healthy, gender-matched, and age-matched controls were measured using a radioimmunoassay kit. Plasma DHEA-S levels in patients were significantly higher than those in healthy controls. In patients who achieved remission after antidepressant treatment, plasma DHEA-S levels significantly declined compared with the levels before treatment. A significant correlation was observed between changes in DHEA-S levels and Absence of Depressive and Anxious Mood scores, which are calculated from the 2-Item Structured Interview Guide for the Hamilton Depression rating as follows: severity of depressive mood and anxiety in patients before and after antidepressant treatment. These findings suggest that plasma DHEA-S levels can be used as a putative indicator of the state of remission in patients with major depressive disorder. Copyright © 2014 John Wiley & Sons, Ltd. Copyright © 2014 John Wiley & Sons, Ltd.

  12. Human liver cytosolic sulfotransferase 2A1-dependent dehydroepiandrosterone sulfation assay by ultra-high performance liquid chromatography-tandem mass spectrometry.

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    Bansal, Sumit; Lau, Aik Jiang

    2016-02-20

    Sulfotransferase 2A1 (SULT2A1) is a major catalyst of the sulfation of dehydroepiandrosterone (DHEA) to dehydroepiandrosterone sulfate (DHEA-S) in human liver cytosol. However, there is a lack of a sensitive and fast analytical method for the human liver cytosolic SULT2A1-dependent DHEA sulfation assay. Therefore, we developed and validated an ultra-high performance liquid chromatography-tandem mass spectrometric (UPLC-MS/MS) method to quantify DHEA-S and used it to optimize the human liver cytosolic SULT2A1-dependent DHEA sulfation assay. DHEA-S and cortisol (internal standard) eluted at 2.95 and 2.75min, respectively. Negative multiple reaction monitoring was used to quantify DHEA-S (m/z 367.3→97.0) and cortisol (m/z 407.2→331.3). No interfering peaks were observed in blank samples. The lower limit of quantification was 0.2pmol DHEA-S and the calibration curve was linear from 0.2 to 200pmol. The intra-day and inter-day accuracy and precision was sulfotransferase enzyme assays, and it is the first UPLC-MS/MS method for determining SULT2A1-dependent DHEA sulfation in human liver cytosol.

  13. A possible link between exercise-training adaptation and dehydroepiandrosterone sulfate- an oldest-old female study

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    Yi-Jen Huang, Mu-Tsung Chen, Chin-Lung Fang, Wen-Chih Lee, Sun-Chin Yang, Chia-Hua Kuo

    2006-01-01

    Full Text Available The purpose of this study was to determine the association between the level of salivary dehydroepiandrosterone sulfate (DHEA-S and the magnitude of adaptation to exercise training in insulin sensitivity for aged females. A group of 16 females, aged 80-93 years old, was divided into 2 groups according to their baseline DHEA-S levels: Lower Halves (N = 8 and Upper Halves (N = 8, and participated in a 4-month exercise intervention trial. Insulin response with an oral glucose tolerance test (OGTT, cholesterol, blood pressure (BP, motor performance, and DHEA-S were determined at baseline and 4 months after the training program. Glucose tolerance and body mass index (BMI remained unchanged with training for both groups. Insulin, fasted cholesterol, diastolic blood pressure, reaction time, and locomotive function were significantly lowered by training only in the Upper Halves group. Changes in the area under curve of insulin (IAUC were negatively correlated with the baseline DHEA-S level (R= - 0.60, P < 0.05. The current study provides the first evidence that oldest-old subjects with low DHEA-S level appear to be poor responders to exercise-training adaptations.

  14. Follicular fluid dehydroepiandrosterone sulfate is a credible marker of oocyte maturity and pregnancy outcome in conventional in vitro fertilization cycles

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    Natachandra M Chimote

    2015-01-01

    Full Text Available Aim: To investigate if the level of dehydroepiandrosterone sulfate (DHEA-s in follicular fluid (FF influences the competence of oocytes to fertilize, develop to the blastocyst stage, and produce a viable pregnancy in conventional in vitro fertilization (IVF cycles. Settings and Design: Prospective study of age-matched, nonpolycystic ovary syndrome (PCOS women undergoing antagonist stimulation protocol involving conventional insemination and day 5 blastocyst transfer. Materials and Methods: FF levels of DHEA-s and E2 were measured by a radio-immuno-assay method using diagnostic kits. Fertilization rate, embryo development to the blastocyst stage and live birth rate were main outcome measures. Cycles were divided into pregnant/nonpregnant groups and also into low/medium/high FF DHEA-s groups. Statistical analysis was done by GraphPad Prism V software. Results: FF DHEA-s levels were significantly higher in pregnant (n = 111 compared to nonpregnant (n = 381 group (1599 ± 77.45 vs. 1372 ± 40.47 ng/ml; P = 0.01. High (n = 134 FF DHEA-s group had significantly higher percentage of metaphase II (MII oocytes (91.5 vs. 85.54 vs. 79.44%, P < 0.0001, fertilization rate (78.86 vs. 74.16 vs. 71.26%, P < 0.0001, cleavage rate (83.67 vs. 69.1 vs. 66.17%, P = 0.0002, blastocyst formation rate (37.15 vs. 33.01 vs. 26.95%, P < 0.0001, and live birth rate (29.85 vs. 22.22 vs. 14.78%, P = 0.017 compared to medium (n = 243 and low (n = 115 FF DHEA-s groups, respectively despite comparable number of oocytes retrieved and number of blastocysts transferred. FF DHEA-s levels correlated significantly with the attainment of MII oocytes (Pearson r = 0.41 and fertilization rates (Pearson r = 0.35. Conclusion: FF DHEA-s level influences the oocyte maturation process and is predictive of fertilization, embryo development to the blastocyst stage and live birth rates in non-PCOS women undergoing conventional IVF cycles.

  15. Attenuated DHEA and DHEA-S response to acute psychosocial stress in individuals with depressive disorders.

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    Jiang, Xiaoling; Zhong, Wen; An, Haiyan; Fu, Mingyu; Chen, Yuanyuan; Zhang, Zhenggang; Xiao, Zhongju

    2017-06-01

    In recent years, a relationship between depression and basal dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEA-S) levels has frequently been suggested, but responses of these adrenal steroids to psychosocial stress have not been examined in individuals with depressive disorders. In this study, we examined salivary DHEA, DHEA-S, and cortisol/DHEA response to the Trier Social Stress Test (TSST) in individuals with depressive disorders and in healthy controls to discover whether the responses of DHEA and DHEA-S to acute psychosocial stress could be a more sensitive marker of HPA dysfunction in depressive disorders. We compared salivary cortisol, DHEA, DHEA-S, and cortisol/DHEA levels to the TSST tests between 38 individuals with depression and 43 healthy controls aged 18.4-25.9 years. Depression severity was assessed by the self-reported Beck Depression Inventory-II (BDI-II). Salivary samples were evaluated at four time points: the baseline (-10 time point), before the TSST started (0 time point), the end of the TSST (+20 time point), and the recovery (+50 time points). No significant differences existed in the basal adrenal hormonal levels between subjects with depressive disorders and controls; however, at the end of TSST, attenuated DHEA and DHEA-S response was identified in subjects with depressive disorders compared to that found in healthy subjects. The differences in the DHEA and DHEA-S levels at the +20 time point, as well as the differences in the cortisol/DHEA at the +50 time point, exhibited negative correlations with depression severity. Attenuated DHEA and DHEA-S response to acute psychosocial stress was identified in subjects with depressive disorders. These findings help us to discover the bi-directional relationship between depression and the hypothalamic-pituitary-adrenal (HPA) axis function, hence furthering our understanding of whether altered DHEA and DHEA-S response to psychosocial stress may be a more sensitive method than

  16. Neuroprotective-Neurotrophic Effect of Endogenous Dehydroepiandrosterone Sulfate During Intense Stress Exposure

    Science.gov (United States)

    2014-06-02

    and neurogenesis [20]. Regarding neuroprotection, DHEA(S) is thought to exert pro-survival effects by modulating gamma-ami- nobutyric acid [18...Experimental evidence does suggest that DHEA(S) treatment yields neurogenesis [20] and neuroprotection [18], as well as NGF overproduction in brain cortex [27...J. Dehydroepiandrosterone (DHEA) stimulates neurogenesis in the hippocampus of the rat, promotes survival of newly formed neurons and prevents

  17. Leukocyte Telomere Length and Serum Levels of High-Molecular-Weight Adiponectin and Dehydroepiandrosterone-Sulfate Could Reflect Distinct Aspects of Longevity in Japanese Centenarians

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    Yuji Aoki MD, PhD

    2017-03-01

    Full Text Available Leukocyte telomere length and serum levels of high-molecular-weight adiponectin and dehydroepiandrosterone-sulfate (DHEA-S were assessed in association with nutrition and performance status (PS in Japanese centenarians. Twenty-three centenarians (five men, 18 women were classified according to their PS 1 (nearly fully ambulatory, n = 2, 2 (in bed less than 50% of daytime, n = 10, 3 (in bed greater than 50%, n = 6, and 4 (completely bedridden, n = 5. Leukocyte telomere length was determined by the hybridization protection assay, and the adiponectin and DHEA-S levels were measured by chemiluminescent enzyme immunoassay. Among variables of PS, body mass index (BMI, albumin, adiponectin, DHEA-S, and telomere length, there were significant correlations between PS and albumin ( r = −.694, p < .01, between telomere length and BMI ( r = .522, p < .05, between adiponectin and BMI ( r = −.574, p < .01, and between DHEA-S and albumin ( r = .530, p < .01. When excluding two cancer-bearing centenarians with short telomere, telomere length significantly correlated with PS ( r = −.632, p < .01. It was indicated that the short leukocyte telomere was associated with poor PS and cancer development and that the adiponectin or DHEA-S was associated with adiposity or nutritional status. Despite a small number of subjects, these biomarkers seemed to reflect distinct aspects of longevity in Japanese centenarians.

  18. Serum DHEA-S concentration correlates with clinical symptoms and neurocognitive function in patients with bipolar II disorder: A case-controlled study.

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    Lee, Sheng-Yu; Wang, Liang-Jen; Chang, Cheng-Ho; Wu, Chih-Ching; Chen, Hsing-Ling; Lin, Shih-Hsien; Chu, Chin-Liang; Lu, Ti; Lu, Ru-Band

    2017-03-06

    Dysregulation of the neuroendocrine system including dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEA-S), and pregnenolone may play a role in the pathophysiology of bipolar II disorder (BP-II). The aims of the current study are to determine (a) the differences in DHEA, DHEA-S and pregnenolone in patients with BP-II and controls; and (b) the correlation of levels of the above hormones, cognitive function, and clinical symptoms. Patients diagnosed with BP-II and healthy controls were recruited from psychiatric department. Blood samples were collected to measure the levels of DHEA, DHEA-S and pregnenolone in all participants, followed by assessment of cognitive function using the Brief Assessment of Cognition in Affective Disorders (BACA). A total of 32 patients BP-II and 30 healthy control subjects were recruited. The BP-II group was found with significantly elder age, fewer years of education, and lower BACA composite scores compared to the healthy controls. The level of DHEA-S was significantly associated with performance in BACA when controlling for age, gender, years of education and having BP-II (P=0.018). The DHEA-S level was significantly correlated with mania score (r=-0.498, P=0.010). Our findings support that serum level of DHEA-S may be a biomarker representing clinical manic symptoms and cognitive performance. Copyright © 2016. Published by Elsevier Inc.

  19. "Maternal serum Dehydroepiandrosterone Sulfate levels and successful labor induction "

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    Modares Gilani M

    2003-06-01

    Full Text Available To evaluate the maternal serum dehydroepiandrosterone sulfate level as a factor associated with the outcome of labor induction. Venous blood was collected from 45 women at the initiation of labor induction. Pregnancies complicated by maternal corticosteriod use, anterpartum chorioamnionitis, or cesarean delivery for indications other than arrest disorders, were excluded from analysis. In 42 women meeting inclusion criteria, induction followed established protocol. Serum dehydroepiandrosterone sulfate levels were measured by radioimmunoassay and correlated with the outcome of each induction attempt. A successful result was defined as progression to active labor. The welch approximate t-test, Mann-Whitney test, Fisher exact test, simple regression, and multiple regression were used for statistical analysis, with P<0.05 considered to be significant. The mean (±standard error dehydroepiandrosterone sulfate level was higher in women who progressed to active labor (n=25 than in those with unsuccessful attempts (n=17, (48,63±6.53 µg/dl versus 26.86±5.17 mg/dl, respectively; p= 0.03. Compared with women with dehydroepiandrosterone sulfate levels above 60 µg/dl, women with lower levels had an unsuccessful induction odds ratio (OR of 6.92 (95% confidence interval 1.74, 32.52, p= 0.01. The OR increased as dehydroepiandrosterone sulfate levels decreased. Dehydroepiandrosterone sulfate may be an important factor in successful labor induction.

  20. Perceived stress at work is associated with attenuated DHEA-S response during acute psychosocial stress.

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    Lennartsson, Anna-Karin; Theorell, Töres; Kushnir, Mark M; Bergquist, Jonas; Jonsdottir, Ingibjörg H

    2013-09-01

    Dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEA-S) have been suggested to play a protective role during acute psychosocial stress, because they act as antagonists to the effects of the stress hormone cortisol. This study aims to investigate whether prolonged psychosocial stress, measured as perceived stress at work during the past week, is related to the capacity to produce DHEA and DHEA-S during acute psychosocial stress. It also aims to investigate whether prolonged perceived stress affects the balance between production of cortisol and DHEA-S during acute psychosocial stress. Thirty-six healthy subjects (19 men and 17 women, mean age 37 years, SD 5 years), were included. Perceived stress at work during the past week was measured by using the Stress-Energy (SE) Questionnaire. The participants were divided into three groups based on their mean scores; Low stress, Medium stress and High stress. The participants underwent the Trier Social Stress Test (TSST) and blood samples were collected before, directly after the stress test, and after 30 min of recovery. General Linear Models were used to investigate if the Medium stress group and the High stress group differ regarding stress response compared to the Low stress group. Higher perceived stress at work was associated with attenuated DHEA-S response during acute psychosocial stress. Furthermore, the ratio between the cortisol production and the DHEA-S production during the acute stress test were higher in individuals reporting higher perceived stress at work compared to individuals reporting low perceived stress at work. There was no statistical difference in DHEA response between the groups. This study shows that prolonged stress, measured as perceived stress at work during the past week, seems to negatively affect the capacity to produce DHEA-S during acute stress. Given the protective functions of DHEA-S, attenuated DHEA-S production during acute stress may lead to higher risk for adverse

  1. Serum DHEA-S increases in dogs naturally infected with Ehrlichia canis.

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    Rondelli, M C H; Munhoz, T D; Catandi, P B; Freschi, C R; Palacios Junior, R J G; Machado, R Z; Tinucci-Costa, M

    2015-06-01

    Adrenocortical disturbances are expected in canine ehrlichiosis due to the immunological challenges caused by infection and consequent inflammation. Thus, this study aimed to evaluate the occurrence of adrenocortical hormonal alterations in dogs naturally infected with Ehrlichia canis (n = 21) as positively confirmed by the presence of anti-E. canis antibodies (Dot-ELISA) and nested PCR (nPCR). Serum dehydroepiandrosterone sulfate (DHEA-S) concentrations were assessed via ELISA before and one hour after ACTH stimulation. Another 10 healthy dogs were subjected to the same stimulation protocol and used as controls. The results revealed that baseline and post-ACTH DHEA-S concentrations were significantly greater in sick dogs, regardless of gender, and this finding illustrates the stress induced by naturally acquired ehrlichiosis in dogs.

  2. Serum dehydroepiandrosterone (DHEA) and DHEA-sulfate (S) levels in medicated patients with major depressive disorder compared with controls.

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    Kurita, Hirofumi; Maeshima, Hitoshi; Kida, Sayaka; Matsuzaka, Hisashi; Shimano, Takahisa; Nakano, Yoshiyuki; Baba, Hajime; Suzuki, Toshihito; Arai, Heii

    2013-04-05

    There is accumulating evidence regarding gender differences in clinical symptoms or response to antidepressants in patients with depression. However, less attention has been given to sex differences in the underlying biological mechanisms of depression. The adrenal androgens, dehydroepiandrosterone (DHEA) and its sulfate derivative (DHEA-S), play a critical role in controlling affect, mood, and anxiety. Changes in serum adrenal androgen levels have been reported in conditions pertaining to stress as well as in psychiatric disorders. The objective of the present study was to investigate differences in serum levels of adrenal androgens in male and female patients with major depressive disorder (MDD). Participants included 90 inpatients with MDD at the psychiatric ward of Juntendo University Koshigaya Hospital who were receiving antidepressants. Serum levels of DHEA and DHEA-S were assessed at the time of admission. Matched controls (based on sex and age) included 128 healthy individuals. First, data from male and female MDD patients and controls were compared. Second, correlations between serum hormone levels and scores on the Hamilton Rating Scale for Depression (HAM-D) of patients with MDD were assessed by gender. In addition, effects of various factors on adrenal androgens were analyzed using multiple regression analysis. Serum DHEA levels were significantly increased in both male and female MDD patients compared with controls. Serum levels of DHEA-S in male patients were significantly decreased compared with male controls, whereas no significant differences were seen in female patients and controls. No significant correlations among adrenal androgens were observed in male patients with MDD, whereas significant positive correlations were found in both male and female controls. No significant correlations were seen between adrenal androgens and HAM-D scores in male or female patients. Multiple regression analysis showed that both hormones were affected by the age

  3. Essential Oil of Japanese Cedar (Cryptomeria japonica Wood Increases Salivary Dehydroepiandrosterone Sulfate Levels after Monotonous Work

    Directory of Open Access Journals (Sweden)

    Eri Matsubara

    2017-01-01

    Full Text Available Employee problems arising from mental illnesses have steadily increased and become a serious social problem in recent years. Wood is a widely available plant material, and knowledge of the psychophysiological effects of inhalation of woody volatile compounds has grown considerably. In this study, we established an experimental method to evaluate the effects of Japanese cedar wood essential oil on subjects performing monotonous work. Two experiment conditions, one with and another without diffusion of the essential oil were prepared. Salivary stress markers were determined during and after a calculation task followed by distribution of questionnaires to achieve subjective odor assessment. We found that inhalation of air containing the volatile compounds of Japanese cedar wood essential oil increased the secretion of dehydroepiandrosterone sulfate (DHEA-s. Slight differences in the subjective assessment of the odor of the experiment rooms were observed. The results of the present study indicate that the volatile compounds of Japanese cedar wood essential oil affect the endocrine regulatory mechanism to facilitate stress responses. Thus, we suggest that this essential oil can improve employees’ mental health.

  4. Monoamines, BDNF, Dehydroepiandrosterone, DHEA-Sulfate, and Childhood Depression—An Animal Model Study

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    O. Malkesman

    2009-01-01

    Full Text Available Basal levels of monoamines and DHEA in four main limbic brain regions were measured in prepubertal Wistar Kyoto (WKY rats (a putative animal model of childhood depression. Basal levels of “Brain-Derived Neurotrophic Factor (BDNF” were also determined in two regions in the hippocampus, compared with Wistar strain controls. In the second phase, we examined the responsiveness of prepubertal WKY rats to different types of chronic antidepressant treatments: Fluoxetine, Desipramine, and dehydroepiandrosterone sulfate (DHEAS. WKY prepubertal rats exhibited different monoamine levels in the limbic system, reduced DHEA levels in the VTA and lower levels of BDNF in the hippocampus CA3 region compared to controls. In prepubertal WKY rats, only treatment with DHEAS produced a statistically significant decrease in immobility, compared to saline-administered controls in the forced swim test. Wistar controls were not affected by any antidepressant. The results imply that DHEA(S and BDNF may be involved in the pathophysiology and pharmacotherapy of childhood depression.

  5. No evidence to support the concept that low serum dehydroepiandrosterone (DHEA) sulfate (s) levels are associated with less oocyte production or lower pregnancy rates.

    Science.gov (United States)

    Borman, E; Check, J H; Mitchell-Williams, J; Cohen, R

    2012-01-01

    To determine if in a population of women with diminished oocyte reserve as evidenced by day 3 serum follicle stimulating hormone (FSH) levels > 12 mIU/ml women with lower dehydroepiandrosterone sulfate (DHEA-s) levels produce fewer oocytes or have lower pregnancy rates following in vitro fertilization-embryo transfer (IVF-ET) compared to women with higher levels. The women were divided into poor responders (producing or = 5 oocytes). Mean DHEA-s levels were compared in poor vs good responders and in the subgroups of those who conceived vs those who did not conceive. The data clearly showed no association with low DHEA-s levels and response to controlled ovarian hyperstimulation or pregnancy rates. In women with elevated serum FSH low DHEA levels do not suggest that supplementation with DHEA would improve response or pregnancy rate. These data do not preclude the possibility that there is a small subset of women with normal oocyte reserve who also fail to respond to controlled ovarian hyperstimulation for some unknown reason and the problem could be remediable by DHEA supplementation.

  6. Perceived stress at work is associated with lower levels of DHEA-S.

    Science.gov (United States)

    Lennartsson, Anna-Karin; Theorell, Töres; Rockwood, Alan L; Kushnir, Mark M; Jonsdottir, Ingibjörg H

    2013-01-01

    It is known that long-term psychosocial stress may cause or contribute to different diseases and symptoms and accelerate aging. One of the consequences of prolonged psychosocial stress may be a negative effect on the levels of dehydroepiandrosterone (DHEA) and its sulphated metabolite dehydroepiandrosterone sulphate (DHEA-S). The aim of this study is to investigate whether levels of DHEA and DHEA-S differ in individuals who report perceived stress at work compared to individuals who report no perceived stress at work. Morning fasting DHEA-S and DHEA levels were measured in serum in a non-stressed group (n = 40) and a stressed group (n = 41). DHEA and DHEA-S levels were compared between the groups using ANCOVA, controlling for age. The mean DHEA-S levels were 23% lower in the subjects who reported stress at work compared to the non-stressed group. Statistical analysis (ANCOVA) showed a significant difference in DHEA-S levels between the groups (p = 0.010). There was no difference in DHEA level between the groups. This study indicates that stressed individual have markedly lower levels of DHEA-S. Given the important and beneficial functions of DHEA and DHEA-S, lower levels of DHEA-S may constitute one link between psychosocial stress, ill health and accelerated ageing.

  7. Perceived stress at work is associated with lower levels of DHEA-S.

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    Anna-Karin Lennartsson

    Full Text Available BACKGROUND: It is known that long-term psychosocial stress may cause or contribute to different diseases and symptoms and accelerate aging. One of the consequences of prolonged psychosocial stress may be a negative effect on the levels of dehydroepiandrosterone (DHEA and its sulphated metabolite dehydroepiandrosterone sulphate (DHEA-S. The aim of this study is to investigate whether levels of DHEA and DHEA-S differ in individuals who report perceived stress at work compared to individuals who report no perceived stress at work. METHODS: Morning fasting DHEA-S and DHEA levels were measured in serum in a non-stressed group (n = 40 and a stressed group (n = 41. DHEA and DHEA-S levels were compared between the groups using ANCOVA, controlling for age. RESULTS: The mean DHEA-S levels were 23% lower in the subjects who reported stress at work compared to the non-stressed group. Statistical analysis (ANCOVA showed a significant difference in DHEA-S levels between the groups (p = 0.010. There was no difference in DHEA level between the groups. CONCLUSIONS: This study indicates that stressed individual have markedly lower levels of DHEA-S. Given the important and beneficial functions of DHEA and DHEA-S, lower levels of DHEA-S may constitute one link between psychosocial stress, ill health and accelerated ageing.

  8. 21 CFR 862.1245 - Dehydroepiandrosterone (free and sulfate) test system.

    Science.gov (United States)

    2010-04-01

    ... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1245 Dehydroepiandrosterone (free and sulfate) test system. (a)...

  9. Serum cortisol and dehydroepiandrosterone-sulfate levels after balneotherapy and physical therapy in patients with fibromyalgia

    Science.gov (United States)

    Semiz, Esra A.; Hizmetli, Sami; Semiz, Murat; Karadağ, Ahmet; Adalı, Merve; Tuncay, Mehmet S.; Alim, Bulent; Hayta, Emrullah; Uslu, Ali U.

    2016-01-01

    Objectives: To investigated serum cortisol and serum dehydroepiandrosterone-sulphate (DHEA-S) levels between fibromyalgia (FMS) patients and a control group, and the effect of balneotherapy (BT) on these hormones. Methods: Seventy-two patients with FMS and 39 healthy volunteers were included in the study. This prospective and cross-sectional study was carried out in the Medical Faculty, Physical Medicine and Rehabilitation Clinic, Cumhuriyet University, Cumhuriyet, Turkey between June 2012 and June 2013. Patients were divided into 2 groups. There were 40 patients in the first group, consisting of BT and physical therapy (PT) administered patients. There were 32 FMS patients in the second group who were only administered PT. Thirty-nine healthy volunteers were enrolled as a control group. Result: Cortisol was observed to be lower in FMS patients compared with the controls (10.10±4.08 μg/dL and 11.78±3.6 μg/dL; p=0.033). Serum DHEA-S level was observed to be lower in FMS patients compared with the controls (89.93±53.96 μg/dL and 143.15±107.92 μg/dL; p=0.015). Average serum cortisol levels of patients receiving BT were determined to be 9.95±3.20 μg/dL before treatment and 9.06±3.77μg/dL after treatment; while average serum DHEA-S levels were 77.60±48.05 μg/dL before treatment, and 76.84±48.71 μg/dL after treatment. No significant changes were determined in serum cortisol and DHEA-S levels when measured again after BT and PT. Conclusion: Low levels of serum cortisol and DHEA-S were suggested to be associated with the physiopathology of FMS. PMID:27146618

  10. [Neuropsychic effects of dehydroepiandrosterone].

    Science.gov (United States)

    Rigaud, A S; Pellerin, J

    2001-04-01

    Dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEA-S) are secreted primarily by the adrenal glands. DHEA could also be a neuroactive steroidal hormone. Because basal levels of DHEA and DHEA-S in humans decrease significantly with age, these hormones have been assumed to be involved in the aging process and in a number of pathologies which develop with aging: immunosenescence, increased mortality, increased incidence of cancer, osteoporosis and cardiovascular diseases. However, its role is still unknown. In humans, cross sectional and longitudinal studies have shown that DHEA might be associated with global measures of well-being and functioning, but positive effects on measures of memory and attention could not be found. Studies investigating DHEA and DHEA-S levels in dementia have produced controversial results. Short-term experimental studies have not shown significant improvement in global measures of well-being and functioning in healthy subjects but have revealed preliminary evidence for mood enhancing and antidepressant effects of DHEA. There is no evidence that DHEA could induce addiction in human beings.

  11. Dehydroepiandrosterone (DHEA) and dehydroepiandrosterone-sulfate (DHEAS) and emotional processing - A behavioral and electrophysiological approach.

    Science.gov (United States)

    do Vale, Sónia; Selinger, Lenka; Martins, João Martin; Bicho, Manuel; do Carmo, Isabel; Escera, Carles

    2015-07-01

    Dehydroepiandrosterone (DHEA) and dehydroepiandrosterone-sulfate (DHEAS) may have mood enhancement effects: higher DHEAS concentrations and DHEA/cortisol ratio have been related to lower depression scores and controlled trials of DHEA administration have reported significant antidepressant effects. The balance between DHEAS and DHEA has been suggested to influence brain functioning. We explored DHEAS, DHEA, cortisol, DHEA/cortisol and DHEAS/DHEA ratios relations to the processing of negative emotional stimuli at behavioral and brain levels by recording the electroencephalogram of 21 young women while performing a visual task with implicit neutral or negative emotional content in an audio-visual oddball paradigm. For each condition, salivary DHEA, DHEAS and cortisol were measured before performing the task and at 30 and 60min intervals. DHEA increased after task performance, independent of the implicit emotional content. With implicit negative emotion, higher DHEAS/DHEA and DHEA/cortisol ratios before task performance were related to shorter visual P300 latencies suggesting faster brain processing under a negative emotional context. In addition, higher DHEAS/DHEA ratios were related to reduced visual P300 amplitudes, indicating less processing of the negative emotional stimuli. With this study, we could show that at the electrophysiological level, higher DHEAS/DHEA and DHEA/cortisol ratios were related to shorter stimulus evaluation times suggesting less interference of the implicit negative content of the stimuli with the task. Furthermore, higher DHEAS/DHEA ratios were related to reduced processing of negative emotional stimuli which may eventually constitute a protective mechanism against negative information overload. Copyright © 2015. Published by Elsevier Inc.

  12. Serum testosterone, DHEA-S and androstenedione levels in acne

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    Hatwal A

    1990-01-01

    Full Text Available Basal serum levels of total testosterone, dehydroepiandosterone sulfate (DHEA, - S and androstenedione (A4 were measured by radioimmunoassay in 100 patients of acne vulgaris, and in 100 age and sex matched acne free healthy subjects. In males with acne the mean serum testosterone levels were marginally and the DHEAS and A4A levels were significantly higher as compared to controls (p. Females with acne had significantly higher levels of testosterone (p< 0.001, DHEA-S (p< 0.001 and (p < 0.01 than controls. Our data suggest that increased adrenal androgen levels in plasma may be responsible for treatment resistant acne vulgarism

  13. Impact of Dehydroepiandrosterone Sulfate on Newborn Leukocyte Telomere Length

    Science.gov (United States)

    Liu, Han; Zhou, Guangdi; Chen, Qian; Ouyang, Fengxiu; Little, Julian; Zhang, Jun; Chen, Dan

    2017-01-01

    The newborn setting of leukocyte telomere length (LTL) likely has important implications for telomere dynamics over the lifespan. However, its determinants are poorly understood. Hormones play an important role during pregnancy and delivery. We hypothesized that exposure to hormones may impact the fetal telomere biology system. To test this hypothesis, cortisol, estradiol, dehydroepiandrosterone sulfate (DHEAS) and reactive oxygen species (ROS) were measured in cord blood of 821 newborns from a prospective study. After accounting for the effects of potential determinants of newborn LTL, a 10-fold increase in DHEAS concentration was associated with a 0.021 increase in T/S ratio of newborn LTL (95% confidence interval: 0.009–0.034, P = 0.0008). For newborns who fell in the lowest quartile of DHEAS level, the mean newborn LTL was estimated to be approximately 2.0% shorter than the newborns in the highest DHEAS concentration quartile (P = 0.0014). However, no association was found between newborn LTL and cortisol or estradiol. As expected, newborns with higher ROS level (ROS > 260 mol/L) had lower LTL compared to that with lower ROS level (ROS ≤ 260 mol/L) (P = 0.007). There was also an inverse relationship between DHEAS and ROS (P programming” effect on the newborn telomere biology system. PMID:28186106

  14. Dehydroepiandrosterone (DHEA) treatment of depression.

    Science.gov (United States)

    Wolkowitz, O M; Reus, V I; Roberts, E; Manfredi, F; Chan, T; Raum, W J; Ormiston, S; Johnson, R; Canick, J; Brizendine, L; Weingartner, H

    1997-02-01

    Dehydroepiandrosterone (DHEA) and its sulfate, DHEA-S, are plentiful adrenal steroid hormones that decrease with aging and may have significant neuropsychiatric effects. In this study, six middle-aged and elderly patients with major depression and low basal plasma DHEA f1p4or DHEA-S levels were openly administered DHEA (30-90 mg/d x 4 weeks) in doses sufficient to achieve circulating plasma levels observed in younger healthy individuals. Depression ratings, as well as aspects of memory performance significantly improved. One treatment-resistant patient received extended treatment with DHEA for 6 months: her depression ratings improved 48-72% and her semantic memory performance improved 63%. These measures returned to baseline after treatment ended. In both studies, improvements in depression ratings and memory performance were directly related to increases in plasma levels of DHEA and DHEA-S and to increases in their ratios with plasma cortisol levels. These preliminary data suggest DHEA may have antidepressant and promemory effects and should encourage double-blind trials in depressed patients.

  15. Walking Training and Cortisol to DHEA-S Ratio in Postmenopause: an Intervention Study.

    Science.gov (United States)

    Di Blasio, Andrea; Izzicupo, Pascal; Di Baldassarre, Angela; Gallina, Sabina; Bucci, Ines; Giuliani, Cesidio; Di Santo, Serena; Di Iorio, Angelo; Ripari, Patrizio; Napolitano, Giorgio

    2017-03-22

    The literature indicates that the plasma cortisol-to-dihydroepiandrosterone-sulfate (DHEA-S) ratio is a marker of health status after menopause, when a decline in both estrogens and DHEA-S, and an increase in cortisol occur. An increase in the cortisol-to-DHEA-S ratio has been positively correlated with metabolic syndrome, all-cause mortality, cancer and other diseases. The aim of this study was to investigate the effects of a walking program on the plasma cortisol-to-DHEA-S ratio in postmenopausal women. Fifty-one postmenopausal women participated in a 13-week supervised walking program, in the metropolitan area of Pescara (Italy), from June to September 2013. Participants were evaluated in April-May and September-October of the same year. The linear mixed model showed that the variation of the log10Cortisol-to-log10DHEA-S ratio was associated with the volume of exercise (p = .03). Participants having lower adherence to the walking program did not have a significantly modified either log10Cortisol, nor log10DHEA-S, while those having the highest adherence had a significant reduction in log10Cortisol (p = .016), and a nearly significant increase in log10DHEA-S (p = .084). Walking training appeared to reduce the plasma log10Cortisol-to-log10DHEA-S ratio, although a minimum level of training was necessary to achieve this significant reduction.

  16. A prospective study on cortisol, dehydroepiandrosterone sulfate, and cognitive function in the elderly

    NARCIS (Netherlands)

    Kalmijn, S; Launer, LJ; Stolk, RP; de Jong, FH; Pols, HAP; Hofman, A; Breteler, MMB; Lamberts, SWJ

    1998-01-01

    The objective of this study was to investigate the relation between the peripheral concentrations of the adrenal steroid hormones cortisol and dehydroepiandrosterone sulfate (DHEAS) and cognitive impairment and decline. A prospective study design was used. The setting was a suburb of Rotterdam, The

  17. Hormonal modulation of novelty processing in women: Enhanced under working memory load with high dehydroepiandrosterone-sulfate-to-dehydroepiandrosterone ratios.

    Science.gov (United States)

    do Vale, Sónia; Selinger, Lenka; Martins, João Martin; Bicho, Manuel; do Carmo, Isabel; Escera, Carles

    2016-11-10

    Several studies have suggested that dehydroepiandrosterone (DHEA) and dehydroepiandrosterone-sulfate (DHEAS) may enhance working memory and attention, yet current evidence is still inconclusive. The balance between both forms of the hormone might be crucial regarding the effects that DHEA and DHEAS exert on the central nervous system. To test the hypothesis that higher DHEAS-to-DHEA ratios might enhance working memory and/or involuntary attention, we studied the DHEAS-to-DHEA ratio in relation to involuntary attention and working memory processing by recording the electroencephalogram of 22 young women while performing a working memory load task and a task without working memory load in an audio-visual oddball paradigm. DHEA and DHEAS were measured in saliva before each task. We found that a higher DHEAS-to-DHEA ratio was related to enhanced auditory novelty-P3 amplitudes during performance of the working memory task, indicating an increased processing of the distracter, while on the other hand there was no difference in the processing of the visual target. These results suggest that the balance between DHEAS and DHEA levels modulates involuntary attention during the performance of a task with cognitive load without interfering with the processing of the task-relevant visual stimulus. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  18. 唾液皮质醇与硫酸脱氢表雄酮测定在海军长航军事作业应激评估中的应用%Evaluation of performance stress among military submarine soldiers by using salivary cortisol,DHEA-S and cortisol/DHEA-S ratio assay

    Institute of Scientific and Technical Information of China (English)

    林松; 成祥; 赵名; 倪伟; 陈国柱; 杨征; 于晓妉

    2014-01-01

    目的:对唾液中皮质醇与硫酸脱氢表雄酮( DHEA-S)含量及其比值的变化在长航军事作业应激中的意义进行评估。方法选择海军某部潜艇官兵40名,分别在远航训练数周后归来时及上岸休整9个月后采集唾液标本,同时采集与海军官兵年龄相当的军事医学科学院研究生部34名男性研究生期终考试期间及全部科目考试结束后1周的唾液标本作为对照,酶联免疫吸附法检测唾液中皮质醇及DHEA-S的浓度,并计算二者间的比值。结果长航作业应激不影响唾液中皮质醇的浓度,但导致DHEA-S水平显著降低,皮质醇与DHEA-S比值增高。而短期考试应激对皮质醇及DHEA-S的水平没有影响,也不影响该比值。结论该研究证实慢性军事作业应激可以显著降低唾液DHEA-S的含量,改变皮质醇与DHEA-S的比值,该比值增高可能是评估慢性应激对机体影响的较敏感的应激标志。而采用唾液标本具有采样简单方便、敏感性良好的特性,可用于应激标志物的检测。%Objective To investigate the significance of salivary cortisol , dehydroepiandrosterone sulfate (DHEA-S) and cortisol/DHEA-S ratio changes for evaluation of military performance stress .Methods Forty submarine soldiers were selected, whose saliva samples were collected separately at the end of long-term dive training and after nine months of relaxation break.In addition, the saliva samples of thirty-four graduate students were collected the moment they finished a three-hour final examination and one week later .The method of ELISA was used to detect the levels of salivary cortisol and DHEA-S and to count their ratio .Results After long-term dive training , the submarine soldiers showed significantly decreased DHEA-S and an increased cortisol/DHEA-S ratio, but the cortisol level did not change very much .In contrast, the final examination stress did not change the level of cortisol , DHEA-S or

  19. Dehydroepiandrosterone and Dehydroepiandrosterone Sulfate: Anabolic, Neuroprotective, and Neuroexcitatory Properties in Military Men

    Science.gov (United States)

    2013-01-01

    8217-methyl-D-aspartate (which mimics action of glutamate), and/or sigma -1 receptors (implicated in brain plasticity)’^; or possibly after it is con- verted to...sulfate (DHEAS) as neuroactive neurosteroids. Proc Nati Acad Sei 1998; 95: 4089-91. 2. Miller WL: Molecular biology of steroid hormone synthesis. Endocr...dependence [published online ahead of print October 31,2011]. Adv Pharmacol Sei . doi: 10.1155/2011/926361. 8. Xu Y, Tanaka M, Chen L, Sokabe M: DHEAS induces

  20. Precipitous Dehydroepiandrosterone Declines Reflect Decreased Physical Vitality and Function.

    Science.gov (United States)

    Rendina, Danielle N; Ryff, Carol D; Coe, Christopher L

    2017-06-01

    Dehydroepiandrosterone (DHEA) and its sulfated form, DHEA-S, peak in young adulthood and then decrease dramatically with age. However, there is extensive variation in this age-related hormone decline, suggesting an early decrement may be associated with lower vitality and be prognostic of poor health in old age. To determine whether DHEA-S and DHEA are correlated with physical indices of vitality, hormone levels were analyzed with respect to clinical health histories, physical functioning including grip strength, gait speed and repetitive standing, and self-reported chronic pain. The participants (N = 1,214) were 35-86 years of age from a nationally representative survey, Midlife Development in the United States. DHEA-S and DHEA below age-expected levels were associated with more chronic illness conditions and self-reported persistent pain and pain sensitivity upon manual palpation. Additionally, lower DHEA-S and DHEA correlated with poorer performance on tests of physical functioning by middle age suggesting a more precipitous decline is already indicative of reduced vigor and physical strength. When considered with respect to age- and gender-typical norms, larger decrements in DHEA-S and DHEA may be causally related to the loss of physical vitality. Conversely, when hormone secretion is sustained in older adults, it conveys reduced risk for the physical weakness and ailments that precede frailty. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  1. Decreased dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) concentrations in plasma of Alzheimer's disease (AD) patients.

    Science.gov (United States)

    Aldred, Sarah; Mecocci, Patrizia

    2010-01-01

    DHEA is secreted by the adrenal cortex and is also a neurosteroid. Its sulfate (DHEAS) is the most abundant steroid in circulation. The levels of both are seen to decline in concentration with age. Evidence is available for altered levels of DHEA and DHEAS in AD but is limited to relatively few studies assessing small cohorts. This study assessed plasma DHEA and DHEAS levels in AD sufferers (n=72) and compared them to age-matched controls (n=72). Plasma DHEA concentrations were significantly lower in AD patients compared to control (4.24+/-0.4 ng/ml for AD; 3.38+/-0.3 ng/ml for control, p=0.027, Mann-Whitney 1-tailed) and DHEA levels were significantly correlated to DHEAS levels in both control and AD conditions (Spearman's rho correlation coefficient=0.635 in controls and 0.467 in AD, pDHEA and DHEAS concentrations in plasma from a large cohort of patients suffering from AD when compared to age-matched controls. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

  2. Simultaneous measurement of endogenous cortisol, cortisone, dehydroepiandrosterone, and dehydroepiandrosterone sulfate in nails by use of UPLC-MS-MS.

    Science.gov (United States)

    Ben Khelil, Mehdi; Tegethoff, Marion; Meinlschmidt, Gunther; Jamey, Carole; Ludes, Bertrand; Raul, Jean-Sébastien

    2011-09-01

    Steroid hormone concentrations are mostly determined by using different body fluids as matrices and applying immunoassay techniques. However, usability of these approaches may be restricted for several reasons, including ethical barriers to invasive sampling. Therefore, we developed an ultra-performance LC-MS-MS method for high-throughput determination of concentrations of cortisol, cortisone, dehydroepiandrosterone (DHEA), and DHEA sulfate (DHEAS) in small quantities of human nails. The method was validated for linearity, limits of detection and quantification, recovery, intra and interassay precision, accuracy, and matrix effect. Samples from 10 adult women were analyzed to provide proof-of-principle for the method's applicability. Calibration curves were linear (r(2) > 0.999) in the ranges 10-5000 pg mg(-1) for cortisol, cortisone, and DHEAS, and 50-5000 pg mg(-1) for DHEA. Limits of quantification were 10 pg mg(-1) for cortisol, cortisone, and DHEAS, and 50 pg mg(-1) for DHEA. The sensitivity and specificity of the method were good, and there was no interference with the analytes. Mean recovery of cortisol, cortisone, DHEA, and DHEAS was 90.5%, 94.1%, 84.9%, and 95.9%, respectively, with good precision (coefficient of variation cortisone, DHEA, and DHEAS, respectively. This method enables measurement of cortisol, cortisone, DHEA, and DHEAS in small quantities of human nails, leading to the development of applications in endocrinology and beyond.

  3. The neurosteroid dehydroepiandrosterone sulfate, but not androsterone, enhances the antidepressant effect of cocaine examined in the forced swim test--Possible role of serotonergic neurotransmission.

    Science.gov (United States)

    Krzascik, Pawel; Zajda, Malgorzata Elzbieta; Majewska, Maria Dorota

    2015-04-01

    One of the mechanisms of cocaine's actions in the central nervous system is its antidepressant action. This effect might be responsible for increased usage of the drug by individuals with mood disorders. Higher endogenous levels of the excitatory neurosteroid dehydroepiandrosterone sulfate (DHEAS) were reported to correlate with successful abstinence from cocaine use in addicts, but a clinical trial showed that supplementation with a high dose of DHEA increased cocaine usage instead. Such ambiguous effects of DHEA(S) could potentially be linked to its influence on the antidepressant effect of cocaine. In this study we tested DHEAS and its metabolite, androsterone, for interactions with cocaine in animal model of depression (forced swim test) and examined the effects of both steroids and cocaine on serotoninergic neurotransmission. All substances were also tested for influence on locomotor activity. A cocaine dose of 5mg/kg, which had no significant effect on locomotor activity, was chosen for the forced swim test. Neither DHEAS nor androsterone showed any antidepressant action in this test, while cocaine manifested a clear antidepressant effect. Androsterone slightly reduced the antidepressant influence of cocaine while DHEAS markedly, dose-dependently enhanced it. Such an effect might be caused by the influence of DHEAS on serotonin neurotransmission, as this steroid decreased serotonin concentration and turnover in the striatum. When DHEAS and cocaine were administered together, the levels of serotonin in the striatum and hippocampus remained unchanged. This phenomenon may explain the additive antidepressant action of DHEAS and cocaine and why co-administration of DHEAS and cocaine increases drug use.

  4. No Difference in Mood and Quality of Life in DHEA-S Deficient Adults with Addison's Disease vs. Type 2 Diabetes Patients with Normal DHEA-S Levels: Implications for Management of These Conditions.

    Science.gov (United States)

    Heald, Adrian H; Walther, Andreas; Davis, Julian R E; Moreno, Gabriela Y C; Kane, John; Livingston, Mark; Fowler, Helen L

    2017-01-01

    Patients with Addison's disease have relatively high rates of depression and anxiety symptoms compared with population-based reference samples. Addison's disease results in deficiency of dehydroepiandrosterone (DHEA) and DHEA-sulfate (DHEA-S). There is considerable debate about the specific effects of DHEA deficiency on energy level and mood. We measured emotional well-being in 16 patients with Addison's disease and a group of 16 hospital attendees with type 2 diabetes. Participants completed the General Health Questionnaire-28 (GHQ-28), the Hospital Anxiety and Depression Scale (HADS), the World Health Organization's quality of life assessment (WHOQOL-BREF) and the Holmes-Rahe life event scale. DHEA-S was low in Addison's patients (Addison's men: 0.5 ± 0.1 μmol/l [normal range: 2.1-10.8] compared with diabetes men: 3.2 ± 1.2 μmol/l; Addison's women: 0.4 ± 0.01 μmol/l [normal range: 1.0-11.5] compared with diabetes women: 2.2 ± 0.71 μmol/l). Testosterone levels were similar in both groups studied. There were no differences in emotional well-being and quality of life (QOL) between patients with Addison's disease and Type 2 Diabetes Mellitus as measured by GHQ-28 (Addison's: 22.4 ± 2.6, Diabetes: 19.6 ± 2.7), HADS Depression (Addison's: 5.4 ± 0.9, Diabetes: 4.5 ± 1.4), HADS Anxiety and WHOQOL-BREF. There were no gender differences in affective symptomatology within the Addison's group. Life event scores were above average in both groups (Addison's: 195 ± 39.6, Diabetes: 131 ± 43.8), but not significant for difference between groups as was GHQ-28 total score. Both groups scored highly on the GHQ-28 and the life event scale, indicative of poorer health perceptions than the general population. This could be due to the chronicity of both disorders. We have not identified any specific effects of DHEA-S deficiency on mood or QOL.

  5. No Difference in Mood and Quality of Life in DHEA-S Deficient Adults with Addison’s Disease vs. Type 2 Diabetes Patients with Normal DHEA-S Levels: Implications for Management of These Conditions

    Science.gov (United States)

    Heald, Adrian H.; Walther, Andreas; Davis, Julian R. E.; Moreno, Gabriela Y. C.; Kane, John; Livingston, Mark; Fowler, Helen L.

    2017-01-01

    Patients with Addison’s disease have relatively high rates of depression and anxiety symptoms compared with population-based reference samples. Addison’s disease results in deficiency of dehydroepiandrosterone (DHEA) and DHEA-sulfate (DHEA-S). There is considerable debate about the specific effects of DHEA deficiency on energy level and mood. We measured emotional well-being in 16 patients with Addison’s disease and a group of 16 hospital attendees with type 2 diabetes. Participants completed the General Health Questionnaire-28 (GHQ-28), the Hospital Anxiety and Depression Scale (HADS), the World Health Organization’s quality of life assessment (WHOQOL-BREF) and the Holmes–Rahe life event scale. DHEA-S was low in Addison’s patients (Addison’s men: 0.5 ± 0.1 μmol/l [normal range: 2.1–10.8] compared with diabetes men: 3.2 ± 1.2 μmol/l; Addison’s women: 0.4 ± 0.01 μmol/l [normal range: 1.0–11.5] compared with diabetes women: 2.2 ± 0.71 μmol/l). Testosterone levels were similar in both groups studied. There were no differences in emotional well-being and quality of life (QOL) between patients with Addison’s disease and Type 2 Diabetes Mellitus as measured by GHQ-28 (Addison’s: 22.4 ± 2.6, Diabetes: 19.6 ± 2.7), HADS Depression (Addison’s: 5.4 ± 0.9, Diabetes: 4.5 ± 1.4), HADS Anxiety and WHOQOL-BREF. There were no gender differences in affective symptomatology within the Addison’s group. Life event scores were above average in both groups (Addison’s: 195 ± 39.6, Diabetes: 131 ± 43.8), but not significant for difference between groups as was GHQ-28 total score. Both groups scored highly on the GHQ-28 and the life event scale, indicative of poorer health perceptions than the general population. This could be due to the chronicity of both disorders. We have not identified any specific effects of DHEA-S deficiency on mood or QOL. PMID:28553251

  6. No Difference in Mood and Quality of Life in DHEA-S Deficient Adults with Addison’s Disease vs. Type 2 Diabetes Patients with Normal DHEA-S Levels: Implications for Management of These Conditions

    Directory of Open Access Journals (Sweden)

    Adrian H. Heald

    2017-05-01

    Full Text Available Patients with Addison’s disease have relatively high rates of depression and anxiety symptoms compared with population-based reference samples. Addison’s disease results in deficiency of dehydroepiandrosterone (DHEA and DHEA-sulfate (DHEA-S. There is considerable debate about the specific effects of DHEA deficiency on energy level and mood. We measured emotional well-being in 16 patients with Addison’s disease and a group of 16 hospital attendees with type 2 diabetes. Participants completed the General Health Questionnaire-28 (GHQ-28, the Hospital Anxiety and Depression Scale (HADS, the World Health Organization’s quality of life assessment (WHOQOL-BREF and the Holmes–Rahe life event scale. DHEA-S was low in Addison’s patients (Addison’s men: 0.5 ± 0.1 μmol/l [normal range: 2.1–10.8] compared with diabetes men: 3.2 ± 1.2 μmol/l; Addison’s women: 0.4 ± 0.01 μmol/l [normal range: 1.0–11.5] compared with diabetes women: 2.2 ± 0.71 μmol/l. Testosterone levels were similar in both groups studied. There were no differences in emotional well-being and quality of life (QOL between patients with Addison’s disease and Type 2 Diabetes Mellitus as measured by GHQ-28 (Addison’s: 22.4 ± 2.6, Diabetes: 19.6 ± 2.7, HADS Depression (Addison’s: 5.4 ± 0.9, Diabetes: 4.5 ± 1.4, HADS Anxiety and WHOQOL-BREF. There were no gender differences in affective symptomatology within the Addison’s group. Life event scores were above average in both groups (Addison’s: 195 ± 39.6, Diabetes: 131 ± 43.8, but not significant for difference between groups as was GHQ-28 total score. Both groups scored highly on the GHQ-28 and the life event scale, indicative of poorer health perceptions than the general population. This could be due to the chronicity of both disorders. We have not identified any specific effects of DHEA-S deficiency on mood or QOL.

  7. [Effects of dehydroepiandrosterone sulfate and dizocilpine on memory trace extinction in aggressive and submissive mice].

    Science.gov (United States)

    Dubrovina, N I; Tomilenko, R A; Obut, T A

    2006-01-01

    It was shown that injections of NMDA receptor antagonist dizocilpine and neurosteroid dehydroepiandrosterone sulfate (DHEAS) and sequential injections of these substances had different effects on learning and extinction of passive avoidance in aggressive and submissive mice. In aggressive mice, dizocilpine impaired and DHEAS did not change learning and retention. However, being injected after dizocilpine, DHEAS blocked the defect of memory trace retrieval induced by dizocilpine. In submissive mice, dizocilpine impaired learning and prolonged extinction of the learned habit. Injection of DHEAS prolonged the extinction in a similar way. Under conditions of sequential injections, DHEAS did not change the suppressive effect of dizocilpine on learning and was not effective in prolongation of extinction.

  8. Measuring DHEA-S in saliva: time of day differences and positive correlations between two different types of collection methods

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    Klein Laura C

    2010-07-01

    Full Text Available Abstract Background The anabolic steroid, dehydroepiandosterone sulfate (DHEA-S, is secreted from the adrenal cortex. It plays a significant role in the body as a precursor to sex steroids as well as a lesser known role in the hypothalamic pituitary adrenal axis (HPA response to stress. DHEA-S can be measured reliably in saliva, making saliva collection a valuable tool for health research because it minimizes the need for invasive sampling procedures (e.g., blood draws. Typical saliva collection methods include the use of plain cotton swab collection devices (e.g., Salivette® or passive drool. There has been some speculation that the plain saliva cotton collection device may interfere with determination of DHEA-S by enzyme immunoassay (EIA bringing this saliva collection method into question. Because of the increasing popularity of salivary biomarker research, we sought to determine whether the cotton swab interferes with DHEA-S determination through EIA techniques. Findings Fifty-six healthy young adult men and women aged 18-30 years came to the lab in the morning (0800 hrs; 14 men, 14 women or late afternoon (1600 hrs; 14 men, 14 women and provided saliva samples via cotton Salivette and passive drool. Passive drool collection was taken first to minimize particle cross contamination from the cotton swab. Samples were assayed for DHEA-S in duplicate using a commercially available kit (DSL, Inc., Webster, TX. DHEA-S levels collected via Salivette and passive drool were positively correlated (r = + 0.83, p Conclusions Results suggest that DHEA-S can be measured accurately using passive drool or cotton Salivette collection methods. Results also suggest that DHEA-S levels change across the day and that future studies need to take this time of day difference into account when measuring DHEA-S.

  9. Treatment with dehydroepiandrosterone sulfate increases NR1 and NR2 subunits of NMDA receptors in rat hippocampus.

    Institute of Scientific and Technical Information of China (English)

    E.DARTOIS; W.PINOTEAU; M.VINCENS

    2004-01-01

    Neurosteroids are present in the central nervous system (CNS) and can be allosteric modulators of neurotransmitter receptors. One of them, the dehydroepiandrosterone sulfate (DHEAS) has been shown to modulate the NMDA receptor, a subtype of glutamate receptor. These NMDA receptors are known to be involved in long-term potentiation and in learning and memory (Tsien 2000). Moreover, DHEAS has been reported

  10. Effects of dehydroepiandrosterone sulfate and progesterone on spatial learning and memory in young and aged mice.

    Science.gov (United States)

    Bodensteiner, Karin J; Stone, Ivan J; Ghiraldi, Loraina L

    2008-07-01

    Young (2-4 months) and aged (14-16 months) male Swiss-Webster albino mice (n = 7 per group) were subcutaneously injected with 20 mg/kg/day dehydroepiandrosterone sulfate (DHEAS), progesterone (P), DHEAS + P, or vehicle control and trained over a 5-day period in a Morris water maze. The subjects were tested 48 hr after training for memory recall as measured by latencies to locate the hidden platform, and trunk blood was collected immediately thereafter. As expected, latency to platform decreased for all groups over the 6 testing days, with aged mice taking longer to reach platform than did young mice. However, results did not support the hypotheses that DHEAS-treated mice would exhibit shorter latencies and that P-treated mice would show longer latencies to platform in comparison with age-matched controls. These results raise doubts about the effectiveness of commercially available supplements claiming to promote enhanced memory in humans.

  11. Dehydroepiandrosterone has strong antifibrotic effects and is decreased in idiopathic pulmonary fibrosis.

    Science.gov (United States)

    Mendoza-Milla, Criselda; Valero Jiménez, Ana; Rangel, Claudia; Lozano, Alfredo; Morales, Violeta; Becerril, Carina; Chavira, Roberto; Ruiz, Víctor; Barrera, Lourdes; Montaño, Martha; Pardo, Annie; Selman, Moisés

    2013-11-01

    Idiopathic pulmonary fibrosis (IPF) is an ageing-related lung disorder characterised by expansion of the myofibroblast population and aberrant lung remodelling. Dehydroepiandrosterone (DHEA), a steroid pro-hormone, decreases with age but an exaggerated decline has been associated with chronic degenerative diseases. We quantified the plasma levels of DHEA and its sulfated form (DHEA-S) in 137 IPF patients and 58 controls and examined the effects of DHEA on human lung fibroblasts. Plasma DHEA/DHEA-S was significantly decreased in male IPF patients (median (range) DHEA: 4.4 (0.2-29.2) versus 6.7 (2.1-15.2) ng · mL(-1), p<0.01; DHEA-S: 47 (15.0-211) versus 85.2 (37.6-247.0) μg · dL(-1), p<0.001), while in females only DHEA-S was significantly decreased (32.6 (15.0-303.0) versus 68.3 (16.4-171) μg · dL(-1), p<0.001). DHEA caused a decrease in fibroblast proliferation and an approximately two-fold increase in fibroblast apoptosis, probably through the intrinsic pathway with activation of caspase-9. This effect was accompanied by upregulation of several pro-apoptotic proteins (Bax and cyclin-dependent kinase-inhibitor CDNK1A) and downregulation of anti-apoptotic proteins, such as cellular inhibitor of apoptosis (c-IAP)1 and c-IAP2. DHEA also caused a significant decrease of transforming growth factor-β1-induced collagen production and fibroblast to myofibroblast differentiation, and inhibited platelet-derived growth factor-induced fibroblast migration. These findings demonstrate a disproportionate decrease of DHEA/DHEA-S in IPF patients and indicate that this molecule has multiple antifibrotic properties.

  12. Gradient HPLC separation of dehydroepiandrosterone (DHEA) from its metabolites and biological congeners: role of tetrahydrofuran in the chromatographic mechanism.

    Science.gov (United States)

    Gergely, András; Horváth, Péter; Szász, György; Veress, Gábor

    2009-08-01

    A three-step gradient reversed-phase high-performance liquid chromatography (RP-HPLC) method was developed for the separation of dehydroepiandrosterone (DHEA), its sulfate ester (DHEA-S), its three C7-oxidized metabolites (7alphaOH-DHEA, 7betaOH-DHEA, 7-keto-DHEA), and its biosynthetic congeners (androstenedione, testosterone, estradiol, pregnenolone). This new method allows the quantitative characterization of DHEA metabolism and biosynthetic transformation under given physiological, pathological, or therapeutically influenced circumstances. Tetrahydrofuran probably acts as a proton acceptor coadsorbent, while isopropanol behaves as a proton donor during the separation of testosterone, estradiol, and the stereoisomers of 7-OH-DHEA.

  13. Dehydroepiandrosterone-Sulfate, Insulin Resistance and Ovarian Volume Estimation in Patients With Polycystic Ovarian Syndrome

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    Chrysi Christodoulaki

    2017-08-01

    Full Text Available Objective: To investigate the potential association of DHEA-S with metabolic and hormonal alterations and with disorders of ovarian morphology.Materials and methods: The present study was based on women with PCOS that attended the Gynaecological Endocrinology – Paediatric and Adolescence Endocrinology Department of our clinic. Overall, 321 patients who met the Rotterdam ESHRE/ ASRM – Sponsored criteria for the definition of PCOS were included. Women’s personal medical history was recorded, anthropometric parameters were assessed and blood was drawn for analysis of metabolic and hormonal parameters. A gynaecological ultrasound was also performed to evaluate ovarian morphology.Results: Correlation analysis revealed a significant negative correlation of DHEA-S with the mean volume of the right and left ovary and with the maximum volume of the largest ovary. This finding remained significant after adjusting for age and BMI (β ± SE = -0.39 ± 0.17, p = 0.023 in the case of mean ovarian volume and β ± SE = -0.36 ± 0.17, p = 0.032 in the case of the maximum volume of the maximum ovarian volume.Conclusion: The findings of our study reveal a clear negative association of DHEA-S with ovarian volume. To date, however, current evidence in this field are restricted to experimental animal models. Future clinical studies are needed in this field to corroborate our findings.

  14. Dehydroepiandrosterone (DHEA Feeding Protects Liver Steatosis in Obese Breast Cancer Rat Model

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    Reza Hakkak

    2017-03-01

    Full Text Available Obesity is a major health problem in the US and globally. Obesity is associated with the risk of cardiovascular disease, type 2 diabetes, cancers, hyperlipidemia, and liver steatosis development. Dehydroepiandrosterone (DHEA is a dietary supplement used as an anti-obesity supplement. Previously, we reported that DHEA feeding protects 7,12-dimethylbenz(aanthracene (DMBA-induced mammary tumors. The objectives of this study were to investigate the effects of obesity and DHEA feeding on liver steatosis, body weight gain, and serum DHEA, DHEA sulfate (DHEA-S, insulin-like growth factor-1 (IGF-1, and insulin-like growth factor binding protein-3 (IGFBP-3 levels. Female Zucker rats were randomly assigned to either a control diet or a control diet with DHEA supplementation for 155 days. Livers were collected for histological examination. Serum was collected to measure DHEA, DHEA-S, IGF-1, and IGFBP-3. Our results show that DHEA-fed rats had significantly less liver steatosis (p < 0.001 than control-fed rats and gained less weight (p < 0.001. DHEA feeding caused significant decreases (p < 0.001 in the serum levels of IGF-1 and IGFBP-3 and significantly increased (p < 0.001 serum levels of DHEA and DHEA-S. Our results suggest that DHEA feeding can protect against liver steatosis by reducing body weight gain and modulating serum IGF-1 and IGFBP-3 levels in an obese breast cancer rat model.

  15. Dehydroepiandrosterone (DHEA) Feeding Protects Liver Steatosis in Obese Breast Cancer Rat Model.

    Science.gov (United States)

    Hakkak, Reza; Bell, Andrea; Korourian, Soheila

    2017-03-20

    Obesity is a major health problem in the US and globally. Obesity is associated with the risk of cardiovascular disease, type 2 diabetes, cancers, hyperlipidemia, and liver steatosis development. Dehydroepiandrosterone (DHEA) is a dietary supplement used as an anti-obesity supplement. Previously, we reported that DHEA feeding protects 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary tumors. The objectives of this study were to investigate the effects of obesity and DHEA feeding on liver steatosis, body weight gain, and serum DHEA, DHEA sulfate (DHEA-S), insulin-like growth factor-1 (IGF-1), and insulin-like growth factor binding protein-3 (IGFBP-3) levels. Female Zucker rats were randomly assigned to either a control diet or a control diet with DHEA supplementation for 155 days. Livers were collected for histological examination. Serum was collected to measure DHEA, DHEA-S, IGF-1, and IGFBP-3. Our results show that DHEA-fed rats had significantly less liver steatosis (p DHEA feeding caused significant decreases (p DHEA and DHEA-S. Our results suggest that DHEA feeding can protect against liver steatosis by reducing body weight gain and modulating serum IGF-1 and IGFBP-3 levels in an obese breast cancer rat model.

  16. Testosterone increases circulating dehydroepiandrosterone sulfate levels in the male rhesus macaque

    Directory of Open Access Journals (Sweden)

    Krystina eSorwell

    2014-06-01

    Full Text Available The adrenal steroid dehydroepiandrosterone (DHEA and its sulfate (DHEAS are two of the most abundant hormones in the human circulation. Furthermore, they are released in a circadian pattern and show a marked age-associated decline. Adult levels of DHEA and DHEAS are significantly higher in males than in females, but the reason for this sexual dimorphism is unclear. In the present study, we administered supplementary androgens (DHEA, testosterone and 5α-dihydrotestosterone [DHT] to aged male rhesus macaques (Macaca mulatta. While this paradigm increased circulating DHEAS immediately after DHEA administration, an increase was also observed following either testosterone or DHT administration, resulting in hormonal profile resembling levels observed in young males in terms of both amplitude and circadian pattern. This stimulatory effect was limited to DHEAS, as an increase in circulating cortisol was not observed. Taken together, these data demonstrate an influence of the hypothalamo-pituitary-testicular axis on adrenal function in males, possibly by sensitizing the zona reticularis to the stimulating action of adrenocorticopic hormone. This represents a plausible mechanism to explain sex differences in circulating DHEA and DHEAS levels, and may have important implications in the development of hormone therapies designed for elderly men and women.

  17. Association of serum dehydroepiandrosterone sulfate and cognition in older adults: sex steroid, inflammatory, and metabolic mechanisms.

    Science.gov (United States)

    Hildreth, Kerry L; Gozansky, Wendolyn S; Jankowski, Catherine M; Grigsby, Jim; Wolfe, Pamela; Kohrt, Wendy M

    2013-05-01

    Dehydroepiandrosterone sulfate (DHEAS) levels and cognitive function decline with age, and a role for DHEAS in supporting cognition has been proposed. Higher DHEAS levels may be associated with better cognitive performance, although potential mechanisms for this relationship are not well established. We performed a cross-sectional study of the relationship between serum DHEAS and three aspects of cognition--executive function, working memory, and processing speed--in 49 men and 54 women, aged 60-88 years, with low serum DHEAS levels. We examined three potential mechanisms of DHEAS action--sex hormone sufficiency, inflammatory status, and glucose regulation. After adjustment for multiple covariates, higher serum DHEAS levels were associated with better working memory (standardized beta coefficient 0.50, p memory in the combined population (standardized beta coefficient -0.22, p DHEAS and cognition is complex and differs by sex and cognitive domain. This study supports the need for further investigations of the sex-specific effects of DHEAS on cognition and its underlying mechanisms of action.

  18. Temporal effects of dehydroepiandrosterone sulfate on memory formation in day-old chicks.

    Science.gov (United States)

    Sujkovic, E; Mileusnic, R; Fry, J P; Rose, S P R

    2007-08-24

    Dehydroepiandrosterone sulfate (DHEAS) has been shown to enhance memory retention in different animal models and in various learning paradigms. In the present study, we investigated the effect of peripherally administered DHEAS on the acquisition, consolidation and retention of memory using a weak version of the one-trial passive avoidance task in day-old chicks. Intraperitoneally administered DHEAS (20 mg/kg) either 30 min before or 30 min and 4.5 h after training on the weakly aversive stimulus, enhanced recall at 24 h following training, suggesting a potentiation of not only the acquisition but also the early and late phases of memory consolidation. In contrast, when DHEAS was administered at 30 min prior to the 24 h retention test there was no memory enhancement, indicating a lack of effect on memory retrieval. Memory recall was unaltered when DHEAS was administered at 30 min before training in a control group trained on a strongly aversive stimulus, confirming memory-specific effects. Interestingly, the memory enhancement appeared to be sex-specific as male chicks showed higher recall than females. These findings provide further evidence that DHEAS enhances memory and may be involved in the temporal cascade of long-term memory formation.

  19. Adrenocorticotropic hormone and dehydroepiandrosterone sulfate levels of rheumatoid arthritis patients treated with glucocorticoids.

    Science.gov (United States)

    Yukioka, Masao; Komatsubara, Yoshio; Yukioka, Kazuhiko; Toyosaki-Maeda, Tomoko; Yonenobu, Kazuo; Ochi, Takahiro

    2006-01-01

    To assess adrenal function with respect to the presence or absence of steroid therapy, we investigated differences in the blood levels of adrenocorticotropic hormone (ACTH) and dehydroepiandrosterone sulfate (DHEAS) in relation to steroid (prednisolone) administration in 123 patients with rheumatoid arthritis (RA). Levels of ACTH and DHEAS were significantly lower in the steroid-treated group than in the non-treated group (ACTH: 11.79 pg/ml vs 27.92 pg/ml) (DHEAS: 418.12 ng/ml vs 883.91 ng/ml) (P<0.0001). We observed no steroid dose-related differences in ACTH levels. However, DHEAS levels showed a slight decrease at a prednisolone dose of 2.5 mg/day, with a significant decrease being observed at a dose of 5 mg/day when statistical adjustments were made for age and sex (P<0.0001). At doses of 7.5 mg/day or greater, DHEAS levels were significantly lower than those for 5 mg/day (P<0.0006). These results suggest that low-dose prednisolone reduces adrenal function in patients with RA. We recommend that doses of prednisolone should be limited to 5 mg/day or less in consideration of adrenal function when treating RA patients. The measurement of ACTH and DHEAS may be useful for evaluating adrenal function in patients with RA.

  20. Role of pregnenolone, dehydroepiandrosterone and their sulfate esters on learning and memory in cognitive aging.

    Science.gov (United States)

    Vallée, M; Mayo, W; Le Moal, M

    2001-11-01

    Aging is a general process of functional decline which involves in particular a decline of cognitive abilities. However, the severity of this decline differs from one subject to another and inter-individual differences have been reported in humans and animals. These differences are of great interest especially as concerns investigation of the neurobiological factors involved in cognitive aging. Intensive pharmacological studies suggest that neurosteroids, which are steroids synthesized in the brain in an independent manner from peripheral steroid sources, could be involved in learning and memory processes. This review summarizes data in animals and humans in favor of a role of neurosteroids in cognitive aging. Studies in animals demonstrated that the neurosteroids pregnenolone (PREG) and dehydroepiandrosterone (DHEA), as sulfate derivatives (PREGS and DHEAS, respectively), display memory-enhancing properties in aged rodents. Moreover, it was recently shown that memory performance was correlated with PREGS levels in the hippocampus of 24-month-old rats. Human studies, however, have reported contradictory results. First, improvement of learning and memory dysfunction was found after DHEA administration to individuals with low DHEAS levels, but other studies failed to detect significant cognitive effects after DHEA administration. Second, cognitive dysfunctions have been associated with low DHEAS levels, high DHEAS levels, or high DHEA levels; while in other studies, no relationship was found. As future research perspectives, we propose the use of new methods of quantification of neurosteroids as a useful tool for understanding their respective role in improving learning and memory impairments associated with normal aging and/or with pathological aging, such as Alzheimer's disease.

  1. Effects of acute and chronic administration of neurosteroid dehydroepiandrosterone sulfate on neuronal excitability in mice.

    Science.gov (United States)

    Svob Strac, Dubravka; Vlainic, Josipa; Samardzic, Janko; Erhardt, Julija; Krsnik, Zeljka

    2016-01-01

    Neurosteroid dehydroepiandrosterone sulfate (DHEAS) has been associated with important brain functions, including neuronal survival, memory, and behavior, showing therapeutic potential in various neuropsychiatric and cognitive disorders. However, the antagonistic effects of DHEAS on γ-amino-butyric acidA receptors and its facilitatory action on glutamatergic neurotransmission might lead to enhanced brain excitability and seizures and thus limit DHEAS therapeutic applications. The aim of this study was to investigate possible age and sex differences in the neuronal excitability of the mice following acute and chronic DHEAS administration. DHEAS was administered intraperitoneally in male and female adult and old mice either acutely or repeatedly once daily for 4 weeks in a 10 mg/kg dose. To investigate the potential proconvulsant properties of DHEAS, we studied the effects of acute and chronic DHEAS treatment on picrotoxin-, pentylentetrazole-, and N-methyl-D-aspartate-induced seizures in mice. The effects of acute and chronic DHEAS administration on the locomotor activity, motor coordination, and body weight of the mice were also studied. We also investigated the effects of DHEAS treatment on [(3)H]flunitrazepam binding to the mouse brain membranes. DHEAS did not modify the locomotor activity, motor coordination, body weight, and brain [(3)H]flunitrazepam binding of male and female mice. The results failed to demonstrate significant effects of single- and long-term DHEAS treatment on the convulsive susceptibility in both adult and aged mice of both sexes. However, small but significant changes regarding sex differences in the susceptibility to seizures were observed following DHEAS administration to mice. Although our findings suggest that DHEAS treatment might be safe for various potential therapeutic applications in adult as well as in old age, they also support subtle interaction of DHEAS with male and female hormonal status, which may underline observed sex

  2. Tardive dyskinesia, dehydroepiandrosterone sulfate and cytochrome P450c17a gene polymorphism in psychiatric inpatients

    NARCIS (Netherlands)

    Ivanova, S.A.; Geers, L.M.; Al Hadithy, A.F.Y.; Pechlivanoglou, P.; Semke, A.V.; Vyalova, N.M.; Fedorenko, O.Y.; Brouwers, J.R.B.J.; Wilffert, B.; Loonen, A.J.M.

    2014-01-01

    Tardive dyskinesia (TD) is a potentially irreversible antipsychoticinduced movement disorder with a prevalence of about 20-30% in psychiatric patients chronically exposed to antipsychotics. A wellknown theory states that TD is related to oxidative stress induced neurotoxicity. Dehydroepiandrosterone

  3. Prognostic value of dehydroepiandrosterone-sulfate and other parameters of adrenal function in acute ischemic stroke.

    Directory of Open Access Journals (Sweden)

    Claudine A Blum

    Full Text Available BACKGROUND AND PURPOSE: Acute stroke has a high morbidity and mortality. We evaluated the predictive value of adrenal function testing in acute ischemic stroke. METHODS: In a cohort of 231 acute ischemic stroke patients, we measured dehydroepiandrosterone (DHEA, DHEA-Sulfate (DHEAS, cortisol at baseline and 30 minutes after stimulation with 1 ug ACTH. Delta cortisol, the amount of rise in the 1 ug ACTH-test, was calculated. Primary endpoint was poor functional outcome defined as modified Rankin scale 3-6 after 1 year. Secondary endpoint was nonsurvival after 1 year. RESULTS: Logistic regression analysis showed that DHEAS (OR 1.21, 95% CI 1.01-1.49, but not DHEA (OR 1.01, 95% CI 0.99-1.04, was predictive for adverse functional outcome. Neither DHEA (OR 0.99, 95% CI 0.96-1.03 nor DHEAS (OR 1.10, 95% CI 0.82-1.44 were associated with mortality. Baseline and stimulated cortisol were predictive for mortality (OR 1.41, 95% CI 1.20-1.71; 1.35, 95% CI 1.15-1.60, but only basal cortisol for functional outcome (OR 1.20, 95% CI 1.04-1.38. Delta cortisol was not predictive for functional outcome (OR 0.86, 95% CI 0.71-1.05 or mortality (OR 0.92, 95% CI 0.72-1.17. The ratios cortisol/DHEA and cortisol/DHEAS discriminated between favorable outcome and nonsurvival (both p<0.0001 and between unfavorable outcome and nonsurvival (p = 0.0071 and 0.0029, but are not independent predictors for functional outcome or mortality in multivariate analysis (adjusted OR for functional outcome for both 1.0 (95% CI 0.99-1.0, adjusted OR for mortality for both 1.0 (95% CI 0.99-1.0 and 1.0-1.01, respectively. CONCLUSION: DHEAS and the cortisol/DHEAS ratio predicts functional outcome 1 year after stroke whereas cortisol levels predict functional outcome and mortality. TRIAL REGISTRATION: ClinicalTrials.gov NCT00390962 (Retrospective analysis of this cohort.

  4. [Dehydroepiandrosterone (DHEA)--youth hormone?].

    Science.gov (United States)

    Zdrojewicz, Z; Kesik, S

    2001-01-01

    Dehydroepiandrosterone (DHEA) and its sulphated metabolite (DHEA-S) are endogenous steroid hormones, synthesized by the adrenal cortex, gonads and CNS. The secretion profile changes with age and depends on the sex. Human DHEA and DHEA-S levels decline linearly and systematically with age and suggest the potential importance of that parameter as a biomarker of ageing. The counteraction of DHEA against atherosclerotic disease, cancer growth, diabetes mellitus, insulin resistance, obesity and the influence on immunological functions are observed in researches. DHEA influences the condition of mind, cognition functions, memory and well-being. DHEA hormonal replacement therapy is expected to lengthen human life by the stoppage of physiological degeneration changes and prevention of age-related clinical disorders.

  5. Dehydroepiandrosterone-induces miR-21 transcription in HepG2 cells through estrogen receptor β and androgen receptor

    Science.gov (United States)

    Teng, Yun; Litchfield, Lacey M.; Ivanova, Margarita M.; Prough, Russell A.; Clark, Barbara J.; Klinge, Carolyn M.

    2014-01-01

    Although oncomiR miR-21 is highly expressed in liver and overexpressed in hepatocellular carcinoma (HCC), its regulation is uncharacterized. We examined the effect of physiologically relevant nanomolar concentrations of dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEA-S) on miR-21 expression in HepG2 human hepatoma cells. 10 nM DHEA and DHEA-S increase pri-miR-21 transcription in HepG2 cells. Dietary DHEA increased miR-21 in vivo in mouse liver. siRNA and inhibitor studies suggest that DHEA-S requires desulfation for activity and that DHEA-induced pri-miR-21 transcription involves metabolism to androgen and estrogen receptor (AR and ER) ligands. Activation of ERβ and AR by DHEA metabolites androst-5-ene-3,17-dione (ADIONE), androst-5-ene-3β,17β-diol (ADIOL), dihydrotestosterone (DHT), and 5α-androstane-3β,17β-diol (3β-Adiol) increased miR-21 transcription. DHEA-induced miR-21 increased cell proliferation and decreased Pdcd4 protein, a bona fide miR-21. Estradiol (E2) inhibited miR-21 expression via ERα. DHEA increased ERβ and AR recruitment to the miR-21 promoter within the VMP1/TMEM49 gene, with possible significance in hepatocellular carcinoma. PMID:24845419

  6. [Dehydroepiandrosterone and the cerebral functions].

    Science.gov (United States)

    Goncharov, N P; Katsiia, G V; Nizhnik, A N

    2006-01-01

    Of all steroidal hormones, dehydroepiandrosterone (DHEA) and its sulphate form, DHEAS, are synthesized by the adrenal glands in the biggest quantities. In this review the authors consider the ways of the synthesis of the neurosteroids, possible mechanisms of the regulation of these processes, and their dynamics under stressful conditions. The paper presents analysis of experimental and clinical data on the role of DHEAS in the manifestation of different cerebral functions. The authors pay special attention to the results of substitutive therapy with DHEA(S) in patients with such CNS functional disorders, as Alzheimer's disease, depression, age-relative memory and sleep disturbances, etc.

  7. Bioverfügbarkeit verschiedener Darreichungsformen von clathriertem Dehydroepiandrosteron (DHEA) gegenüber nativem DHEA bei Frauen mit Nebennierenrindeninsuffizienz

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    Günther, Susann Margot Louise

    2006-01-01

    Bei Patientinnen mit chronischer Nebennierenrindeninsuffizienz liegt - neben dem Mangel an Glukokortikoiden und Mineralokortikoiden - ein Defizit an adrenalen Androgenen, nämlich Dehydroepiandrosteron (DHEA) und seinem Sulfatester DHEA-S vor. Obwohl DHEA und DHEA-S mengenmäßig die bedeutendsten Hormone der menschlichen Nebennierenrinde sind, gehören sie noch nicht zur standardisierten Substitutionstherapie bei Ausfall der Nebennierenrinde. In Untersuchungen der letzten Jahre konnte jedoch wie...

  8. Opposing effects of dehydroepiandrosterone sulfate and free testosterone on metabolic phenotype in women with polycystic ovary syndrome.

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    Lerchbaum, Elisabeth; Schwetz, Verena; Giuliani, Albrecht; Pieber, Thomas R; Obermayer-Pietsch, Barbara

    2012-11-01

    To study the association of adrenal and ovarian androgen levels with metabolic parameters in a large cohort of women with polycystic ovary syndrome (PCOS). Cross-sectional study. Outpatient clinic of an academic hospital. Six hundred twenty-two women with PCOS. None. Analysis of the association of endocrine dehydroepiandrosterone sulfate (DHEAS) and free testosterone (FT) parameters with metabolic measurements. In multivariate adjusted logistic regression analyses, the odds ratio (OR) for insulin resistance was statistically significantly higher (4.42, range: 2.26-8.67) for women with PCOS who had elevated FT levels compared with the women with normal DHEAS and FT levels (reference group). We found no statistically significant differences when women with PCOS with elevated DHEAS or a combined elevation of DHEAS and FT levels were compared with the reference group. Women with PCOS and a high DHEAS/FT ratio had a more beneficial metabolic profile compared with the women with a low DHEAS/FT ratio. In multivariate adjusted binary logistic regression analyses, we found a statistically significantly lower risk for insulin resistance in the women with PCOS in the highest DHEAS/FT-ratio quartile compared with women with PCOS in the lowest quartile (OR 0.35, range: 0.14-0.89). Our results suggest that the distinction between adrenal and ovarian hyperandrogenism is important when evaluating metabolic risk in PCOS. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  9.  Dehydroepiandrosterone sulfate, osteoprotegerin and its soluble ligand sRANKL and bone metabolism in girls with anorexia nervosa

    Directory of Open Access Journals (Sweden)

    Zofia Ostrowska

    2012-09-01

    Full Text Available  Background:Only scarce data exist concerning the relationship between dehydroepiandrosterone (DHEA and/or its sulfate form DHEAS and bone status in adolescents with anorexia nervosa (AN.Aim:We investigated whether a relationship existed between DHEAS and bone metabolism (as assessed based on serum osteocalcin [OC], and collagen type I cross-linked carboxy-terminal telopeptide [CTx]. We also aimed to establish whether the above mentioned relationship might be affected by osteoprotegerin (OPG and its soluble ligand sRANKL.Material/Methods:Fifty-six female patients with AN and 21 healthy female subjects aged 13 to 16 years participated in the study. Serum DHEAS, OC, CTx, OPG and sRANKL were measured by ELISA.Results:Our female patients with AN demonstrated significant suppression of DHEAS and bone markers, an increase in OPG and sRANKL levels, and a reduction of the OPG/sRANKL ratio. DHEAS, CTx and the OPG/sRANKL ratio correlated positively with BMI. A significant positive correlation was also observed between DHEAS and the OPG/sRANKL ratio, OC and the OPG/sRANKL ratio, and CTx and sRANKL. The correlation was negative in the case of DHEAS and CTx, DHEAS and sRANKL, CTx and the OPG/sRANKL ratio, and sRANKL and the OPG/sRANKL ratio.Discussion/DHEAS suppression in girls with anorexia nervosa was associated with a decrease in the levels of bone markers, an increase in OPG and sRANKL concentrations and a significant decrease in the OPG/sRANKL ratio. DHEAS suppression in girls with anorexia nervosa might have a harmful effect on their bone tissue, probably via a shift in the OPG/RANKL ratio toward a functional excess of sRANKL.

  10. Effect of Regular Yogic Training on Growth Hormone and Dehydroepiandrosterone Sulfate as an Endocrine Marker of Aging

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    Sridip Chatterjee

    2014-01-01

    Full Text Available Growth hormone (GH and dehydroepiandrosterone sulfate (DHEAS secretion decline with advancing age and are associated with the symptoms of aging. Yogic texts claimed that regular practice of yoga may restore and maintain general endocrinological properties in the human body. Objective of the Study. To observe the effect of yogic training for twelve weeks on basal level of GH and DHEAS in middle aged group. Method. Forty-five untrained volunteers were divided into two groups, that is, yoga practicing (experimental: male 15, age 42.80 ± 7.43 yrs; female 8, age 44.75 ± 8.40 yrs and waitlisted control group (male 15, age 41.67 ± 7.87 yrs; female 7, age 45.43 ± 7.00 yrs. The experimental group underwent combined yogic practices daily in the morning for 6 days/week for 12 weeks, whereas control group continued their usual routine activities. Standing height, body weight, body mass index, and basal level of GH and DHEAS were measured before commencement and after six and twelve weeks of yogic training period. The repeated measure ANOVA was used for data analysis. Results. 12 weeks of yogic training produces a significant increase in GH and DHEAS for both male and female groups as compared to their baseline data, whereas no as such changes were observed in the control group. Conclusion. Combined approach of graded yogic training may be beneficial for maintaining the basal level of GH and DHEAS in the human body, thus promoting healthy aging.

  11. Enhancement of zidovudine uptake by dehydroepiandrosterone sulfate in rat syncytiotrophoblast cell line TR-TBT 18d-1.

    Science.gov (United States)

    Nishimura, Tomohiro; Seki, Yoshiaki; Sato, Kazuko; Chishu, Takuya; Kose, Noriko; Terasaki, Tetsuya; Kang, Young-Sook; Sai, Yoshimichi; Nakashima, Emi

    2008-10-01

    AZT (3'-azido-3'-deoxythymidine; zidovudine), which is used for the prevention of mother-to-child transmission of HIV-1, is transplacentally transferred to the fetus across the blood-placenta barrier, which is composed of syncytiotrophoblasts. We recently showed that apical uptake of AZT by syncytiotrophoblasts is mediated by saturable transport system(s) in the TR-TBT 18d-1 cell line, and the cellular accumulation of AZT was increased in the presence of dehydroepiandrosterone sulfate (DHEAS). Here, we aimed to clarify the mechanism of this effect of DHEAS. Inhibitors of efflux transporters, including breast cancer resistance protein, P-glycoprotein, and multidrug resistance proteins, had little effect on the cellular accumulation of AZT in TR-TBT 18d-1. Kinetic study revealed that the rate constant for AZT uptake was greatly increased in the presence of 1 mM DHEAS. These results suggested that the effect of DHEAS was because of enhancement of the uptake process(es), rather than inhibition of efflux. When AZT uptake was analyzed according to the Michaelis-Menten equation, the estimated Michaelis constant, Km, for AZT uptake in the presence of 1 mM DHEAS was lower than that in its absence, whereas maximum uptake velocity, Vmax, and nonsaturable uptake clearance, kns, were similar in the presence and absence of DHEAS, indicating that DHEAS may change the recognition characteristics of the transporter for AZT in TR-TBT 18d-1. Thus, the increase of AZT uptake in TR-TBT 18d-1 cells in the presence of DHEAS was concluded to be because of a DHEAS-induced change in the affinity of AZT uptake system, although the transporter responsible for AZT uptake has not been identified.

  12. Altered regulation of IL-6 production with normal aging. Possible linkage to the age-associated decline in dehydroepiandrosterone and its sulfated derivative.

    Science.gov (United States)

    Daynes, R A; Araneo, B A; Ershler, W B; Maloney, C; Li, G Z; Ryu, S Y

    1993-06-15

    Normal aging in humans has been recently shown to be accompanied by reduced control over production of the multifunctional cytokine IL-6. This cytokine was reported to be quantitatively elevated in most serum samples obtained from "normal" elderly humans. In the present investigation, we report that IL-6 levels are elevated in serum samples obtained from aged mice, and its spontaneous production could also be easily detected in culture supernatants of unstimulated lymphoid cells obtained from aged, but not mature, adult donors. Spontaneous production of IL-6 was consistently observed in culture supernatants of lymphoid cells from both the spleen and mesenteric lymph nodes from aged donors, but was absent from supernatants derived from their peripheral lymph nodes. In aged mice, the reduced regulation of IL-6 production could be effectively prevented and/or reversed by supplementing aging animals with dehydroepiandrosterone sulfate, a steroid hormone whose endogenous production is known to decline with advancing age in all species tested. It was also established that serum obtained from old dehydroepiandrosterone sulfate-treated mice contained lower (normal) levels of serum amyloid P substance (an acute phase reactant), reduced levels of serum Ig (all classes and isotypes) and lower titers of tissue-specific autoantibodies than untreated aged controls. Therefore, a number of well described, age-related conditions, some of which could be contributing to the pathologic phenotype of old age, may actually represent secondary effects to this age-associated change in IL-6 production.

  13. Association between Serum Cortisol and DHEA-S Levels and Response to Antipsychotic Treatment in Schizophrenia

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    Zoja Babinkostova

    2015-02-01

    Full Text Available BACKGROUND: Previous studies suggested that alterations in serum cortisol and DHEA-S levels may play a role in the pathophysiology of schizophrenia. AIM: To compare serum cortisol and DHEA-S levels between patients with schizophrenia and healthy controls and to evaluate their association with the response to antipsychotic treatment. MATERIAL AND METHODS: In this clinical prospective study were included 60 patients with schizophrenia and 40 healthy age and sex matched control subjects. Clinical evaluation of patients was performed using the Positive and Negative Symptom Scale. A questionnaire for socio-demographic and clinical data collection was used. For the purposes of the study, the examined group was divided in two subgroups: responders and nonresponders. Serum cortisol and DHEA-S levels were measured at baseline in all participants and after 3 and 6 weeks of the antipsychotic treatment in patients with schizophrenia. RESULTS: Patients with schizophrenia had significantly higher serum cortisol and DHEA-S levels in comparison to the control group. Responders had significantly higher serum cortisol and DHEA-S levels compared with nonresponders. CONCLUSION: Elevated serum cortisol and DHEA-S levels may play a role in the pathophysiology of schizophrenia and they may be related to positive response to antipsychotic treatment in patients with schizophrenia.

  14. Dehydroepiandrosterone (DHEA)--a precursor steroid or an active hormone in human physiology.

    Science.gov (United States)

    Traish, Abdulmaged M; Kang, H Paco; Saad, Farid; Guay, Andre T

    2011-11-01

    The circulation of large amounts of dehydroepiandrosterone (DHEA) and its sulfated derivative (DHEA-S) suggests a physiological role in human physiology. In the central nervous system, DHEA is considered a neurosteroid with a wide range of functions. The goal of this review is to discuss metabolism, biochemical, and physiological mechanism of DHEA action and the potential role of DHEA in aging and in ameliorating a host of pathological conditions, associated with aging. We examined preclinical and clinical data reported in various studies from the available literature concerning the effects of DHEA in normal and pathological conditions. Data reported in the literature were analyzed, reviewed, and discussed. DHEA mediates its action via multiple signaling pathways involving specific membrane receptors and via transformation into androgen and estrogen derivatives (e.g., androgens, estrogens, 7α and 7β DHEA, and 7α and 7β epiandrosterone derivatives) acting through their specific receptors. These pathways include: nitric oxide synthase activation, modulation of γ-amino butyric acid receptors, N-methyl D-aspartate, receptors sigma receptors (Sigma-1), differential expression of inflammatory factors, adhesion molecules and reactive oxygen species, among others. Clinical and epidemiological studies suggested that low DHEA levels might be associated with ischemic heart disease, endothelial dysfunction, atherosclerosis, bone loss, inflammatory diseases, and sexual dysfunction. Most importantly, no significant adverse or negative side effects of DHEA were reported in clinical studies of men and women. DHEA modulates endothelial function, reduces inflammation, improves insulin sensitivity, blood flow, cellular immunity, body composition, bone metabolism, sexual function, and physical strength in frailty and provides neuroprotection, improves cognitive function, and memory enhancement. DHEA possesses pleiotropic effects and reduced levels of DHEA and DHEA-S may be

  15. A pilot study employing Dehydroepiandrosterone (DHEA) in the treatment of chronic fatigue syndrome.

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    Himmel, P B; Seligman, T M

    1999-04-01

    Patients with chronic fatigue syndrome (CFS) frequently associate the disease onset with a period of high physical and/or emotional stress. Alterations in hypothalamic-pituitary adrenal axis (HPA) function have been demonstrated. Although Cortisol production in patients with CFS has proven to be low, Dehydroepiandrosterone (DHEA) production has not been measured. DHEA output may be altered in this population. The purpose of this uncontrolled, prospective, 6 month study of 23 white women, ages 35-55 was to identify CFS patients with suboptimal serum levels of DHEA-sulphate (DHEA-S), defined as DHEA-S DHEA. DHEA-S levels were re-measured after 4-6 weeks of oral DHEA therapy (25 mg). If DHEA-S remained DHEA was given. Physical and psychological impairment and disability status were measured by the MHAQII before DHEA intervention and at 3-month intervals. Of initially screened patients with CFS, 76% (116 of 153) were ages 35-55, and 89% (103 of 116) had suboptimal (DHEA-S.Supplementation with DHEA to CFS patients lead to a significant reduction in the symptoms of CFS: pain (improved by 18%, p = 0.035), fatigue (decreased by 21%, p = 0.009)), activities of daily living (improved by 8.5%, p = 0.058), helplessness (decreased by 11%, p = 0.015), anxiety (decreased by 35%, p memory (improved by 17%, p DHEA to this population in a controlled setting.

  16. [ROLE OF CAPSAICIN-SENSITIVE NERVES IN THE REGULATION OF DEHYDROEPIANDROSTERONE SULFATE BLOOD CONTENT UNDER NORMAL AND FRUCTOSE-INDUCED METABOLIC SYNDROME].

    Science.gov (United States)

    Spiridonov, V K; Tolochko, Z S; Ovcjukova, M V; Kostina, N E; Obut, T A

    2015-08-01

    The effects of the stimulation of capsaicin-sensitive nerves (capsaicin, 1 mg/kg, s/c) and their eafferentation (capsaicin, 150 mg/kg, s/c) on the blood content of dehydroepiandrosterone sulfate (DHEAS) was investigated in normal rats and rats with fructose-induced metabolic syndrome (12.5% fructose solution, 10 weeks). An increase in blood of tryglyceride, lipid peroxidation, glucose (fasting and after loading glucose, 2 mg/kg, i/p) was considered as symptoms of metabolic syndrome. It was shown that in normal rats drinking tap water the stimulation of capsaicin-sensitive nerves resulted in the increase of DHEAS content while their deafferentation reduced the concentration of this hormone in the blood. The fructose diet caused the decrease in content of DHEAS, triglyceridemia, lipid peroxidation, impaired tolerance glucose. In rats with the metabolic syndrome the stimulation capsaicin-sensitive nerves prevented the fructose-induced decrease of DHEAS content as well as decreased the symptoms of metabolic syndrome. In fructose fed rats the stimulation-induced effects were prevented by the deafferentation of capsaicin-sensitive nerves. It is suggested that capsaicin-sensitive nerves contribute both to the regulation of blood content of DHEAS under normal and fructose-induced metabolic syndrome.

  17. Dehydroepiandrosterone (DHEA) prevents the prostanoid imbalance in mesenteric bed of fructose-induced hypertensive rats.

    Science.gov (United States)

    Peredo, Horacio A; Mayer, Marcos; Faya, Ileana R; Puyó, Ana M; Carranza, Andrea

    2008-10-01

    In previous studies we reported an altered prostanoid (PR) release-pattern in mesenteric vessels in fructose (F)-overloaded rats, an experimental model of insulin resistance and hypertension. Dehydroepiandrosterone (DHEA) and its precursor Dehydroepiandrosterone sulfate (DHEA-S) are the most abundant circulating steroid hormones produced by the adrenal and recent studies in both cells and animals suggest that DHEA may have acute non-genomic actions that mimic both metabolic and vascular actions of insulin. This study was to analyze in F-overloaded rats, the effects of DHEA treatment on arterial blood pressure and the PR production in mesenteric vessels and aorta. Male 6 week-old Sprague-Dawley rats were randomly divided in four groups: a control group (C), a DHEA (30 mg/kg/sc/48 h)-treated group (D), a fructose (10% w/v in drinking water)-fed group (F), and both treatments simultaneously group (FD). The systolic blood pressure (SBP) was measured by tail cuff method and glycemia and triglyderidemia were measured by enzymatic assays. The mesenteric beds of all groups were dissected, and incubated in Krebs solution. The PR released were measured by HPLC. F overload increased SBP and triglyceridemia and decreased the mesenteric vasodilatory PR release. DHEA treatment prevented the increment in SBP and triglyceridemia and decreased vasoconstrictor PR in F-treated rats. DHEA normalize the PGI(2)/TX ratio, diminished in F-overloaded rats, through the decrease in thromboxane (TX) production and this could be one of the mechanisms by which DHEA prevented the slight hypertension in F-animals.

  18. The effects of dehydroepiandrosterone (DHEA)/DHEA-sulfate (DHEAS) on the contraction responses of the clitoral cavernous smooth muscle from female rabbits.

    Science.gov (United States)

    Lee, Shin Young; Myung, Soon Chul; Lee, Moo Yeol; Kim, Tae Hyoung; Kim, Sae Chul; Kim, Kyung Do; Park, Soo Hyun; Kim, Won Yong

    2009-10-01

    Dehydroepiandrosterone (DHEA) is a multifunctional steroid that is increasingly available as a supplement aimed at improving libido and well-being in postmenopausal women in the recent times. Together with its sulfate version, DHEA-sulfate (DHEAS), it is the most abundant steroid in humans. The clitoris is an important component of the female sexual response, with its increased vascular response during sexual arousal that results in erection. To elucidate the direct effects of DHEA/DHEAS on the vasomotor reactivity of the rabbit clitoral cavernosum. Twenty New Zealand white female rabbits weighing approximately 2.5-3 kg were used in the study. The contractile response of clitoral cavernous smooth muscle strips in response to phenylephrine (PE; 10(-9)-10(-4) M) were observed in rabbits. Additionally, DHEA/DHEAS effects on phenylephrine-induced contraction and/or acetylcholine-induced relaxation of phenylephrine-induced contraction were measured. DHEA/DHEAS did not elicit any remarkable response in the resting state. However, both DHEA and DHEAS evoked dose-dependent relaxations of PE-induced contraction. The contractile responses to high potassium were significantly decreased in the DHEA/DHEAS-pretreated strips, compared with the DHEA/DHEAS-nontreated strips. Additionally, contractions by Bay K 8644 (10(-7)-10(-6) M) treatment were also significantly inhibited by DHEA/DHEAS. DHEA-induced relaxation responses were stronger than DHEAS-induced relaxation responses. Various K channel blockers, tetraethylammonium (TEA; 1 mM, 10 mM), 4-aminopyridine (10 microM) and glibenclamide (10 microM) did not affect the DHEA/DHEAS-induced relaxation on muscle strips contracted by PE. Relaxation responses by acetylcholine or sodium nitroprusside (SNP) were not changed after DHEA/DHEAS pretreatment. DHEA/DHEAS was found to induce a relaxation response in rabbit clitoral cavernosal smooth muscle, and this is thought to be mediated by direct inhibition of a voltage-dependent calcium

  19. Associations between dehydroepiandrosterone (DHEA) levels, pituitary volume, and social anxiety in children.

    Science.gov (United States)

    Murray, Cynthia R; Simmons, Julian G; Allen, Nicholas B; Byrne, Michelle L; Mundy, Lisa K; Seal, Marc L; Patton, George C; Olsson, Craig A; Whittle, Sarah

    2016-02-01

    Early timing of adrenarche, associated with relatively high levels of dehydroepiandrosterone (DHEA) and its sulphate (DHEA-S) in children, has been linked with mental health problems, particularly anxiety. However, little is known about possible neurobiological mechanisms underlying this association. The pituitary gland is a key component of the hypothalamic-pituitary-adrenal (HPA) axis, the activation of which triggers the onset of adrenarche. The purpose of this study was to examine the extent to which pituitary gland volume mediated the relationship between levels of DHEA/DHEA-S relative to age (i.e., adrenarcheal timing) and symptoms of anxiety in 95 children (50 female, M age 9.50 years, SD 0.34 years). Relatively high DHEA and DHEA-S (DHEA/S) levels were found to be associated with larger pituitary gland volumes. There was no significant direct effect of relative DHEA/S levels on overall symptoms of anxiety. However, results supported an indirect link between relatively high DHEA/S levels and symptoms of social anxiety, mediated by pituitary gland volume. No sex differences were observed for any relationship. Our findings suggest that neurobiological mechanisms may be partly responsible for the link between relatively early adrenarche and anxiety symptoms in children. One possible mechanism for this finding is that an enlarged pituitary gland in children experiencing relatively advanced adrenarche might be associated with hyper-activity/reactivity of the HPA axis. Further research is needed to understand the role of stress in the link between adrenarcheal timing and HPA-axis function, especially in relation to the development of anxiety symptoms in children and adolescents. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. The neurosteroid dehydroepiandrosterone (DHEA) and its metabolites alter 5-HT neuronal activity via modulation of GABAA receptors.

    Science.gov (United States)

    Gartside, S E; Griffith, N C; Kaura, V; Ingram, C D

    2010-11-01

    Dehydroepiandrosterone (DHEA) and its metabolites, DHEA-sulphate (DHEA-S) and androsterone, have neurosteroid activity. In this study, we examined whether DHEA, DHEA-S and androsterone, can influence serotonin (5-HT) neuronal firing activity via modulation of γ-aminobutryic acid (GABA(A)) receptors. The firing of presumed 5-HT neurones in a slice preparation containing rat dorsal raphe nucleus was inhibited by the GABA(A) receptor agonists 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridinyl-3-ol (THIP) (25 μM) and GABA (100 μM). DHEA (100 and 300 μM) and DHEA-S (1, 10 and 100 μM) caused a rapid and reversible attenuation of the response to THIP. DHEA (100 μM) and DHEA-S (100 μM) also attenuated the effect of GABA. Androsterone (10 and 30 μM) markedly enhanced the inhibitory response to THIP (25 μM). The effect was apparent during androsterone administration but persisted and even increased in magnitude after drug wash-out. The data indicate that GABA(A) receptor-mediated regulation of 5-HT neuronal firing is sensitive to negative modulation by DHEA and its metabolite DHEA-S is sensitive to positive modulation by the metabolite androsterone. The effects of these neurosteroids on GABA(A) receptor-mediated regulation of 5-HT firing may underlie some of the reported behavioural and psychological effects of endogenous and exogenous DHEA.

  1. Dehydroepiandrosterone sulfate mediates activation of transcription factors CREB and ATF-1 via a Gα11-coupled receptor in the spermatogenic cell line GC-2.

    Science.gov (United States)

    Shihan, Mazen; Kirch, Ulrike; Scheiner-Bobis, Georgios

    2013-12-01

    Dehydroepiandrosterone sulfate (DHEAS) is a circulating steroid produced in the adrenal cortex, brain, and gonads. Whereas a series of investigations attest to neuroprotective effects of the steroid in the brain, surprisingly little is known about the physiological effects of DHEAS on cells of the reproductive system. Here we demonstrate that DHEAS acting on the spermatogenic cell line GC-2 induces a time- and concentration-dependent phosphorylation of c-Src and Erk1/2 and activates the transcription factors activating transforming factor-1 (ATF-1) and cyclic AMP-responsive element binding protein (CREB). These actions are consistent with the non-classical signaling pathway of testosterone and suggest that DHEAS is a pro-androgen that is converted into testosterone in order to exert its biological activity. The fact, however, that steroid sulfatase mRNA was not detected in the GC-2 cells and the clear demonstration of DHEAS-induced activation of Erk1/2, ATF-1 and CREB after silencing the androgen receptor by small interfering RNA (siRNA) clearly contradict this assumption and make it appear unlikely that DHEAS has to be converted in the cytosol into a different steroid in order to activate the kinases and transcription factors mentioned. Instead, it is likely that the DHEAS-induced signaling is mediated through the interaction of the steroid with a membrane-bound G-protein-coupled receptor, since silencing of Guanine nucleotide-binding protein subunit alpha-11 (Gnα11) leads to the abolition of the DHEAS-induced stimulation of Erk1/2, ATF-1, and CREB. The investigation presented here shows a hormone-like activity of DHEAS on a spermatogenic cell line. Since DHEAS is produced in male and female reproductive organs, these findings could help to define new roles for DHEAS in the physiology of reproduction.

  2. Changes in DHEA-s levels during the first year of treatment in patients with clinical burnout are related to health development.

    Science.gov (United States)

    Lennartsson, Anna-Karin; Theorell, Töres; Kushnir, Mark M; Jonsdottir, Ingibjörg H

    2016-10-01

    The regenerative hormone DHEA-S was measured in 122 patients with clinical burnout during their first year of treatment. Relations between change of DHEA-S levels and development in health were investigated. About half of the patients exhibited increased DHEA-S levels during the year, while the other half exhibited decreased levels. There was no difference in burnout symptoms or associated health status at baseline between subsequent DHEA-S increasing and DHEA-S decreasing groups. Greater reduction in the burnout symptoms was observed in patients in who DHEA-S levels increased during the year, than in the patients in who DHEA-S levels decreased. Relative change of DHEA-S and direction of the change during the year both predicted burnout symptoms at the end of the year. In addition, patients with increased DHEA-S levels had better self-rated health, vitality and well-being. Our data suggest that changes in DHEA-S are associated with prognosis for the outcome in burnout patients.

  3. Effects of Methylphenidate and Bupropion on DHEA-S and Cortisol Plasma Levels in Attention-Deficit Hyperactivity Disorder

    Science.gov (United States)

    Lee, Moon-Soo; Yang, Jae-Won; Ko, Young-Hoon; Han, Changsu; Kim, Seung-Hyun; Lee, Min-Soo; Joe, Sook-Haeng; Jung, In-Kwa

    2008-01-01

    We evaluated plasma levels of DHEA-S and cortisol before and after treating ADHD patients with one of two medications: methylphenidate (n = 12) or bupropion (n = 10). Boys with ADHD (combined type) were evaluated with the Korean ADHD rating scale (K-ARS) and the computerized ADHD diagnostic system (ADS). All assessments were measured at baseline…

  4. Effects of Methylphenidate and Bupropion on DHEA-S and Cortisol Plasma Levels in Attention-Deficit Hyperactivity Disorder

    Science.gov (United States)

    Lee, Moon-Soo; Yang, Jae-Won; Ko, Young-Hoon; Han, Changsu; Kim, Seung-Hyun; Lee, Min-Soo; Joe, Sook-Haeng; Jung, In-Kwa

    2008-01-01

    We evaluated plasma levels of DHEA-S and cortisol before and after treating ADHD patients with one of two medications: methylphenidate (n = 12) or bupropion (n = 10). Boys with ADHD (combined type) were evaluated with the Korean ADHD rating scale (K-ARS) and the computerized ADHD diagnostic system (ADS). All assessments were measured at baseline…

  5. Dehydroepiandrosterone and its Sulfate brJoint Statement by the German Society for Gynecological Endocrinology and Reproductive Medicine [DGGEF] and the German Professional Association of Gynecologists [BVF])

    OpenAIRE

    Rabe T; Ahrendt HJ; Albring C; Bachmann A; Bitzer J; Blume-Peytavi U; Egarter C; Hinney B; Kentenich H; König K; Merki Feld G; Merkle E; Mueck AO; Rossmanith WG; Sänger N

    2015-01-01

    Dehydroepiandrosterone (DHEA) is the most frequent circulating steroid hormone in humans. It is formed in the reticular zone of the adrenal glands to 90 95% and, to a lower extent in the gonads and the brain where DHEA acts as neuro-steroid. There is an interconversion of DHEA to DHEAS in both directions. DHEAS levels in the blood are approximately 300 times higher in comparison to free DHEA levels. The DHEA peak levels are reached in the early morning hours whereas DHEAS is not subject to...

  6. Effects of dehydroepiandrosterone on cognition : an electrophysiological approach

    OpenAIRE

    Fernandes, Sónia Isabel do Vale, 1973-

    2016-01-01

    Tese de doutoramento, Medicina (Endocrinologia), Universidade de Lisboa, Faculdade de Medicina, 2016 Dehydroepiandrosterone (DHEA) and dehydroepiandrosterone-sulfate (DHEAS) physiologic role remain controversial. Central nervous system and behavioral effects have been described. DHEA and DHEAS have been hypothesised to play a role in cortical organization and brain maturation and suggested to have memory, attention and mood enhancement effects in humans. A neuro-stimulatory action and an a...

  7. Dehydroepiandrosterone and age-related cognitive decline

    OpenAIRE

    Sorwell, Krystina G.; Urbanski, Henryk F.

    2009-01-01

    In humans the circulating concentrations of dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS) decrease markedly during aging, and have been implicated in age-associated cognitive decline. This has led to the hypothesis that DHEA supplementation during aging may improve memory. In rodents, a cognitive anti-aging effect of DHEA and DHEAS has been observed but it is unclear whether this effect is mediated indirectly through conversion of these steroids to estradiol. Moreover, despite the de...

  8. Proinflammatory cytokines and DHEA-S in women with fibromyalgia: impact of psychological distress and menopausal status

    Directory of Open Access Journals (Sweden)

    Sturgeon JA

    2014-12-01

    Full Text Available John A Sturgeon,1 Beth D Darnall,1 Heather L Zwickey,2 Lisa J Wood,3 Douglas A Hanes,2 David T Zava,4 Sean C Mackey1 1Stanford University School of Medicine, Department of Anesthesiology, Perioperative and Pain Medicine, Palo Alto, CA, USA; 2Helfgott Research Institute, National College of Natural Medicine, Portland, OR, USA; 3MGH Institute of Health Professions, Boston, MA, USA; 4ZRT Laboratories, Beaverton, OR, USA Abstract: Though fibromyalgia is not traditionally considered an inflammatory disorder, evidence for elevated inflammatory processes has been noted in this disorder in multiple studies. Support for inflammatory markers in fibromyalgia has been somewhat equivocal to date, potentially due to inattention to salient patient characteristics that may affect inflammation, such as psychiatric distress and aging milestones like menopause. The current study examined the relationships between proinflammatory cytokines and hormone levels, pain intensity, and psychological distress in a sample of 34 premenopausal and postmenopausal women with fibromyalgia. Our results indicated significant relationships between interleukin-8 and ratings of pain catastrophizing (r=0.555, P<0.05, pain anxiety (r=0.559, P<0.05, and depression (r=0.551, P<0.05 for postmenopausal women but not premenopausal women (r<0.20 in all cases. Consistent with previous studies, ratios of interleukin-6 to interleukin-10 were significantly lower in individuals with greater levels of depressive symptoms (r=−0.239, P<0.05. Contrary to previous research, however, dehydroepiandrosterone sulfate did not correlate with pain intensity or psychological or biological variables. The results of the current study highlight the importance of psychological functioning and milestones of aging in the examination of inflammatory processes in fibromyalgia. Keywords: fibromyalgia, cytokines, psychological distress, inflammation

  9. Hypoxia and dehydroepiandrosterone in old age: a mouse survival study

    Directory of Open Access Journals (Sweden)

    Quillard Janine

    2006-12-01

    Full Text Available Abstract Background Survival remains an issue in pulmonary hypertension, a chronic disorder that often affects aged human adults. In young adult mice and rats, chronic 50% hypoxia (11% FIO2 or 0.5 atm induces pulmonary hypertension without threatening life. In this framework, oral dehydroepiandrosterone was recently shown to prevent and reverse pulmonary hypertension in rats within a few weeks. To evaluate dehydroepiandrosterone therapy more globally, in the long term and in old age, we investigated whether hypoxia decreases lifespan and whether dehydroepiandrosterone improves survival under hypoxia. Methods 240 C57BL/6 mice were treated, from the age of 21 months until death, by normobaric hypoxia (11% FIO2 or normoxia, both with and without dehydroepiandrosterone sulfate (25 mg/kg in drinking water (4 groups, N = 60. Survival, pulmonary artery and heart remodeling, weight and blood patterns were assessed. Results In normoxia, control mice reached the median age of 27 months (median survival: 184 days. Hypoxia not only induced cardiopulmonary remodeling and polycythemia in old animals but also induced severe weight loss, trembling behavior and high mortality (p Conclusion Dehydroepiandrosterone globally reduced what may be called an age-related frailty induced by hypoxic pulmonary hypertension. This interestingly recalls an inverse correlation found in the prospective PAQUID epidemiological study, between dehydroepiandrosterone blood levels and mortality in aged human smokers and former smokers.

  10. Dehydroepiandrosterone and its Sulfate brJoint Statement by the German Society for Gynecological Endocrinology and Reproductive Medicine [DGGEF] and the German Professional Association of Gynecologists [BVF

    Directory of Open Access Journals (Sweden)

    Rabe T

    2015-01-01

    Full Text Available Dehydroepiandrosterone (DHEA is the most frequent circulating steroid hormone in humans. It is formed in the reticular zone of the adrenal glands to 90– 95% and, to a lower extent in the gonads and the brain where DHEA acts as neuro-steroid. There is an interconversion of DHEA to DHEAS in both directions. DHEAS levels in the blood are approximately 300 times higher in comparison to free DHEA levels. The DHEA peak levels are reached in the early morning hours whereas DHEAS is not subject to a circadian rhythm. Hence, DHEAS is well suitable for analysis in serum. DHEA is a universal precursor for the formation of androgen and estrogen in peripheral tissues. They contain enzyme systems such as 3beta-HSDH for the formation of androstenedione, 17alpha-hydroxysteroid dehydrogenase for the synthesis of testosterone and aromatase for estrogen-synthesis. Maximum levels of DHEA/DHEAS are reached between 20 and 30 years of age. At the age of 70 or older DHEAS levels can be up to 75% lower.br Mode of action: DHEA acts predominantly as steroid precursor in the biosynthesis of androgenic and estrogenic sex steroids. There have been no DHEA/ DHEAS receptors identified yet. DHEA and DHEAS bind and activate several receptors including ER-alpha and ER-beta, peroxisome-proliferator activated receptors, PXR (pregnant-X-receptor, AUTO (constitutive androstane receptor and beyond that membrane receptors as neuro-steroids like NMDA receptors (N-methyl- D-aspartate, glutamate as positive allosteric modulator of the GABAA receptor and negative allosteric modulator. DHEA/DHEAS has a variety of dose independent effects like immune-modulation, effects on haemostasis, the lipid- and carbohydrate metabolism, bone health and mental health.br Pharmacology: The pharmacokinetic of DHEA depends on gender, dosing (25–50, 100 or 300 mg/day oral, no further increase of DHEA or DHEAS concentrations, respectively, and the route of application (oral, transdermal, vaginal. The oral

  11. Effects of dehydroepiandrosterone (DHEA) on cardiovascular risk factors in older women with frailty characteristics.

    Science.gov (United States)

    Boxer, R S; Kleppinger, A; Brindisi, J; Feinn, R; Burleson, J A; Kenny, A M

    2010-07-01

    this analysis was to investigate the effects of dehydroepiandrosterone (DHEA) on cardiovascular risk factors in older women with frailty characteristics. the study was a double-blind, randomised, placebo-controlled trial of 99 women (mean 76.6 +/- 6.0 year) with the low DHEA-S level and frailty. participants received 50 mg/day DHEA or placebo for 6 months; all received calcium (1,000-1,200 mg/day diet) and supplement (combined) and cholecalciferol (1,000 IU/day). Women participated in 90-min twice weekly exercise regimens, either chair aerobics or yoga. assessment of outcome variables included hormone levels (DHEA-S, oestradiol, oestrone, testosterone and sex hormone-binding globulin (SHBG)), lipid profiles (total cholesterol, high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol and triglycerides), body composition measured by dual energy absorptiometry, glucose levels and blood pressure (BP). eighty-seven women (88%) completed 6 months of study; 88% were pre-frail demonstrating 1-2 frailty characteristics and 12% were frail with > or =3 characteristics. There were significant changes in all hormone levels including DHEA-S, oestradiol, oestrone and testosterone and a decline in SHBG levels in those taking DHEA supplements. In spite of changes in hormone levels, there were no significant changes in cardiovascular risk factors including lipid profiles, body or abdominal fat, fasting glucose or BP. research to date has not shown consistent effects of DHEA on cardiovascular risk, and this study adds to the literature that short-term therapy with DHEA is safe for older women in relation to cardiovascular risk factors. This study is novel in that we recruited women with evidence of physical frailty.

  12. Dehydroepiandrosterone (DHEA) and the aging brain: flipping a coin in the "fountain of youth".

    Science.gov (United States)

    Racchi, Marco; Balduzzi, Carla; Corsini, Emanuela

    2003-01-01

    The physiological role of dehydroepiandrosterone (DHEA) and its sulphated ester DHEA(S) has been studied for nearly 2 decades and still eludes final clarification. The major interest in DHEA derives from its unique pattern of activity. Its levels exhibit a dramatic age-related decline that supports significant involvement of DHEA(S) in the aging process. Particularly relevant to the aging process is the functional decline that involves memory and cognitive abilities. DHEA is derived mainly from synthesis in the adrenal glands and gonads. It can also be detected in the brain where it is derived from a synthesis that is independent from peripheral steroid sources. For this reason DHEA and other steroid molecules have been named "neurosteroids." Pharmacological studies on animals provided evidence that neurosteroids could be involved in learning and memory processes because they can display memory-enhancing properties in aged rodents. However, human studies have reported contradictory results that so far do not directly support the use of DHEA in aging-related conditions. As such, it is important to remember that plasma levels of DHEA(S) may not reflect levels in the central nervous system (CNS), due to intrinsic ability of the brain to produce neurosteroids. Thus, the importance of neurosteroids in the memory process and in age-related cognitive impairment should not be dismissed. Furthermore, the fact that the compound is sold in most countries as a health food supplement is hampering the rigorous scientific evaluation of its potential. We will describe the effect of neurosteroids, in particular DHEA, on neurochemical mechanism involved in memory and learning. We will focus on a novel effect on a signal transduction mechanism involving a classical "cognitive kinase" such as protein kinase C. The final objective is to provide additional tools to understand the physiological role and therapeutic potentials of neurosteroids in normal and/or pathological aging, such as

  13. Novel mechanisms for DHEA action

    National Research Council Canada - National Science Library

    Prough, Russell A; Clark, Barbara J; Klinge, Carolyn M

    2016-01-01

    Dehydroepiandrosterone (3β-hydroxy-5-androsten-17-one, DHEA), secreted by the adrenal cortex, gastrointestinal tract, gonads, and brain, and its sulfated metabolite DHEA-S are the most abundant endogeneous circulating steroid hormones...

  14. Dehydroepiandrosterone (DHEA): hypes and hopes.

    Science.gov (United States)

    Rutkowski, Krzysztof; Sowa, Paweł; Rutkowska-Talipska, Joanna; Kuryliszyn-Moskal, Anna; Rutkowski, Ryszard

    2014-07-01

    Dehydroepiandrosterone (DHEA) and its sulfated form dehydroepiandrosterone sulfate (DHEAS) are the most abundant circulating steroid hormones in humans. In animal studies, their low levels have been associated with age-related involuntary changes, including reduced lifespan. Extrapolation of animal data to humans turned DHEA into a 'superhormone' and an 'anti-aging' panacea. It has been aggressively marketed and sold in large quantities as a dietary supplement. Recent double-blind, placebo-controlled human studies provided evidence to support some of these claims. In the elderly, DHEA exerts an immunomodulatory action, increasing the number of monocytes, T cells expressing T-cell receptor gamma/delta (TCRγδ) and natural killer (NK) cells. It improves physical and psychological well-being, muscle strength and bone density, and reduces body fat and age-related skin atrophy stimulating procollagen/sebum production. In adrenal insufficiency, DHEA restores DHEA/DHEAS and androstenedione levels, reduces total cholesterol, improves well-being, sexual satisfaction and insulin sensitivity, and prevents loss of bone mineral density. Normal levels of CD4+CD25(hi) and FoxP3 (forkhead box P3) are restored. In systemic lupus erythematosus, DHEA is steroid-sparing. In an unblinded study, it induced remission in the majority of patients with inflammatory bowel disease. DHEA modulates cardiovascular signalling pathways and exerts an anti-inflammatory, vasorelaxant and anti-remodelling effect. Its low levels correlate with increased cardiovascular disease and all-cause mortality. DHEA/DHEAS appear protective in asthma and allergy. It attenuates T helper 2 allergic inflammation, and reduces eosinophilia and airway hyperreactivity. Low levels of DHEAS accompany adrenal suppression. It could be used to screen for the side effects of steroids. In women, DHEA improves sexual satisfaction, fertility and age-related vaginal atrophy. Many factors are responsible for the inconsistent

  15. Transport of the placental estriol precursor 16α-hydroxy-dehydroepiandrosterone sulfate (16α-OH-DHEAS) by stably transfected OAT4-, SOAT-, and NTCP-HEK293 cells.

    Science.gov (United States)

    Schweigmann, H; Sánchez-Guijo, A; Ugele, B; Hartmann, K; Hartmann, M F; Bergmann, M; Pfarrer, C; Döring, B; Wudy, S A; Petzinger, E; Geyer, J; Grosser, G

    2014-09-01

    16α-Hydroxy-dehydroepiandrosterone sulfate (16α-OH-DHEAS) mainly originates from the fetus and serves as precursor for placental estriol biosynthesis. For conversion of 16α-OH-DHEAS to estriol several intracellular enzymes are required. However, prior to enzymatic conversion, 16α-OH-DHEAS must enter the cells by carrier mediated transport. To identify these carriers, uptake of 16α-OH-DHEAS by the candidate carriers organic anion transporter OAT4, sodium-dependent organic anion transporter SOAT, Na(+)-taurocholate cotransporting polypeptide NTCP, and organic anion transporting polypeptide OATP2B1 was measured in stably transfected HEK293 cells by LC-MS-MS. Furthermore, the study aimed to localize SOAT in the human placenta. Stably transfected OAT4-HEK293 cells revealed a partly sodium-dependent transport for 16α-OH-DHEAS with an apparent Km of 23.1 ± 5.1 μM and Vmax of 485.0 ± 39.1 pmol/mg protein/min, while stably transfected SOAT- and NTCP-HEK293 cells showed uptake only under sodium conditions with Km of 319.0 ± 59.5 μM and Vmax of 1465.8 ± 118.8 pmol/mg protein/min for SOAT and Km of 51.4 ± 9.9 μM and Vmax of 1423.3 ± 109.6 pmol/mg protein/min for NTCP. In contrast, stably transfected OATP2B1-HEK293 cells did not transport 16α-OH-DHEAS at all. Immunohistochemical studies and in situ hybridization of formalin fixed and paraffin embedded sections of human late term placenta showed expression of SOAT in syncytiotrophoblasts, predominantly at the apical membrane as well as in the vessel endothelium. In conclusion, OAT4, SOAT, and NTCP were identified as carriers for the estriol precursor 16α-OH-DHEAS. At least SOAT and OAT4 seem to play a functional role for the placental estriol synthesis as both are expressed in the syncytiotrophoblast of human placenta.

  16. The role of dehydroepiandrosterone (DHEA) in schizophrenia.

    Science.gov (United States)

    Vuksan-Ćusa, Bjanka; Šagud, Marina; Radoš, Iva

    2016-03-01

    Neurosteroid dehydropiandrosterone (DHEA) and its sulphate (DHEAS) are reported to have modulatory effects on neuronal excitabillity and synaptic plasticity. DHEA and DHEAS are synthesized in central and peripheral nervous system from cholesterol or steroidal precursors imported from peripheral sources. There is accumulating evidence that alterations in DHEA(S) levels may be involved in the pathophysiology of schizophrenia. The possible effects of DHEA(S) as augmentation therapy in schizophrenia, related to psychological and somatic aspects of this disease, are discussed.

  17. Effect of dehydroepiandrosterone (DHEA) on Akt and protein kinase C zeta (PKCζ) phosphorylation in different tissues of C57BL6, insulin receptor substrate (IRS)1(-/-), and IRS2(-/-) male mice fed a high-fat diet.

    Science.gov (United States)

    Aoki, Kazutaka; Tajima, Kazuki; Taguri, Masataka; Terauchi, Yasuo

    2016-05-01

    We have previously reported that dehydroepiandrosterone (DHEA) suppresses the activity and mRNA expression of the hepatic gluconeogenic enzyme glucose-6-phosphatase (G6Pase), and hepatic glucose production in db/db mice. Tyrosine phosphorylation levels of Insulin receptor substrate (IRS)1 and IRS2 reportedly differ between the liver and muscle tissue and the effect of DHEA on insulin signaling has not been elucidated. Therefore, we examined DHEA's effect on the liver and muscle tissue of IRS1(-/-) and IRS2(-/-) mice. Eight-week-old male C57BL6, IRS1(-/-), and IRS2(-/-) mice were fed a high-fat diet (HFD), or an HFD containing 0.2% DHEA for 4 weeks. In a separate experiment, 8-week-old male C57BL6 mice were fed an HFD or an HFD containing 0.2% androstenedione for 4 weeks. In an insulin tolerance test, DHEA administration decreased the initial plasma glucose levels in the C57BL6, IRS1(-/-), and IRS2(-/-) mice but did not decrease the ratios to the basal blood glucose level. Although DHEA administration increased Akt phosphorylation in the liver of the C57BL6, IRS1(-/-), and IRS2(-/-) mice, androstenedione administration did not increase Akt phosphorylation in the liver of C57BL6 mice. DHEA administration did not increase Akt and PKCζ phosphorylation in the muscle tissue of C57BL6, IRS1(-/-), or IRS2(-/-) mice. However, androstenedione administration increased Akt and PKCζ phosphorylation in the muscle tissue of C57BL6 mice. These findings suggest that the effect of DHEA on insulin action in the liver is self-mediated by DHEA or DHEA sulfate (DHEA-S) in the presence of IRS1, IRS2, or both. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Dehydroepiandrosterone biosynthesis, metabolism, biological effects, and clinical use (analytical review)

    OpenAIRE

    Goncharov, N. P.; G. V. Katsiya

    2015-01-01

    The review presents the fundamental information on the metabolism of dehydroepiandrosterone (DHEA), its biological role and possibilities of its use for replacement therapy. There were studied species differences in the synthesis of DHEA in the adrenal cortex. It was found that DHEA and DHEA-sulfate are produced only by the adrenal glands of humans and monkeys, including lower monkeys. Their biosynthesis involves the following steps: cholesterol → pregnenolone → 17-hydroxypregnenolone → DHEA....

  19. Dehydroepiandrosterone (DHEA) supplementation for cognitive function in healthy elderly people.

    Science.gov (United States)

    Grimley Evans, J; Malouf, R; Huppert, F; van Niekerk, J K

    2006-10-18

    In view of the theoretical possibility of beneficial effects of DHEA or DHEAS in retarding age-associated deterioration in cognitive function, we have reviewed studies in this area. To establish whether administration of DHEA, or its sulphate, DHEAS, improves cognitive function or reduces the rate of decline of cognitive function in normal older adults. Trials were identified from a last updated search of the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 10 October 2005 using the terms dhea*, prasterone, dehydroepiandrosterone*. In addition MEDLINE, EMBASE, PsycINFO and CINAHL were searched to find trials with volunteers who had no or minor memory complaints. Relevant journals, personal communications and conference abstracts were searched for randomized controlled trials investigating the effects of DHEA/S on cognition in older adults. All randomized placebo-controlled trials enrolling people aged over 50 without dementia and to whom DHEA/S in any dosage was administered for more than one day were considered for inclusion in the review. Data for the specified outcomes were independently extracted by two reviewers (JGE and RM) and cross-checked. Any discrepancies were discussed and resolved. No data pooling was undertaken owing to the lack of availability of the relevant statistics. Only three studies provided results from adequate parallel-group data. Barnhart 1999 enrolled perimenopausal women with complaints of decreased well-being and, using three cognitive measures, found no significant effect of DHEA compared with placebo at 3 months. Wolf 1998b enrolled 75 healthy volunteers (37 women and 38 men aged 59-81) in a study of the effect of DHEA supplements on cognitive impairment induced by stress; after two weeks of treatment, placebo group performance deteriorated significantly on a test of selective attention following a psychosocial stressor (pDHEA group (p=0.85). However, when compared with placebo, DHEA was associated with

  20. The expression of serum steroid sex hormones and steroidogenic enzymes following intraperitoneal administration of dehydroepiandrosterone (DHEA) in male rats.

    Science.gov (United States)

    Song, Lijie; Tang, Xue; Kong, Yili; Ma, Haitian; Zou, Sixiang

    2010-03-01

    The adrenals of humans and primates could secrete large amounts of dehydroepiandrosterone (DHEA) and its sulphate ester (DHEA-S) in the circulation, which act as precursors of active steroid hormones in a long series of peripheral target intracrine tissues. The marked decline of serum DHEA and DHEA-S concentrations with age in humans has been incriminated in the development of various pathologies. Therefore, this study aims to provide detailed information on the effects of the intraperitoneal injection of DHEA on circulating steroid hormones and their metabolites and their trade-off relationship over 24 h in male rats. In this study, 100 healthy adult male Sprague-Dawley (SD) rats were randomly divided into three groups: control, 25 mg kg(-1) DHEA-treated and 100 mg kg(-1) DHEA-treated. The animals were sacrificed at 0, 1.5, 3, 6, 12 or 24 h, and the samples were collected for subsequent analysis. Total cholesterol (TC) markedly decreased 3h after the administration of 100 mg kg(-1) DHEA, but markedly increased 12h after administration. The DHEA-S, progesterone (P), testosterone (T), oestradiol (E(2)), cortisol (Cor) and aldosterone (Ald) concentrations also markedly increased after DHEA administration, with serum DHEA-S, T, E(2) and Cor levels peaking at 1.5 h. Over time, steroid hormone levels were depressed, but serum Cor and Ald levels were markedly elevated relative to the control group at 24 h. Furthermore, DHEA treatment produced a significant increase in P450scc, 17beta-HSDIII, CYP17alpha and 3beta-HSD mRNA expression at 1.5 h, but a decided decrease in P450scc and StAR mRNA expression at 12 and 24 h, and CYP17alpha and 17beta-HSDIII expression at 12 h in the 100 mg kg(-1) DHEA group. In total, the results of the present study indicate that DHEA at high pharmacological doses may affect steroid through an effect on steroidogenic enzymes. Copyright 2009 Elsevier Inc. All rights reserved.

  1. [Dehydroepiandrosterone and brain functioning].

    Science.gov (United States)

    Goncharov, N P; Katsiia, G V; Nizhnik, A N

    2005-01-01

    The adrenal glands synthesize dehydroepiandrosterone (DHEA) and its sulphate form (DHEAS) more intensively than they do other steroid hormones. Researchers are interested in these hormones for several reasons. Firstly, for some years they have been trying to find the reason for DHEA and DHEAS to be synthesized and present in the organism in such high concentrations. Secondly, their attention have been attracted by age-dependent regression of DHEA, which is strictly determined. Thirdly, despite longstanding efforts of scientists, the physiological role and spectrum of the biological activity of DHEA is still unclear. Evidence of that DHEA and DHEAS can be synthesized in situ in the brain tissue, received in rat experiments, urged researchers to clarify the role of these neurosteroids in the CNS. The presented review covers ways of neurosteroid synthesis, possible mechanisms of the regulation of these processes, and their dynamics under the condition of stress. The authors analyze experimental and clinical observations undertaken with a goal to clarify a possible role of DHEA in the manifestation of various brain functions. Special attention is payed to ambiguous results of modern studies, dedicated to replacement therapy of various disorders of CNS functioning (Alzheimer's disease, depression, age-specific memory impairment, sleep disturbance etc.) with DHEAS.

  2. Androgen therapy with dehydroepiandrosterone.

    Science.gov (United States)

    Buvat, Jacques

    2003-11-01

    The physiological role of dehydroepiandrosterone (DHEA) and DHEA sulphate (DHEAS) is poorly understood. It depends in a large part on their transformation into testosterone and estradiol. The capacity of DHEA as a neurosteroid, the recent discovery of putative specific DHEA receptors on endothelial and vascular smooth muscle cells, the steady decrease of DHEA production from the 40s on, together with certain human epidemiologic data as well as various beneficial effects of DHA supplementation in rodents have suggested the possibility that this steroid is involved in cognitive and memory, metabolic and vascular, immune and sexual functions and in their aging. However, epidemiologic studies are conflicting, and no well-designed clinical trials have definitely substantiated the role of DHEA in these functions in humans, or the utility and safety of DHEA supplementation. However, beneficial effects seem plausible in women with several conditions according to the results of double-blind placebo-controlled trials: the dose of 30 to 50 mg seems beneficial to the mood, sense of well being and sexual desire and activity of women with adrenal insufficiency. The only long-term trial of supplementation devoted to women over 60 reported significant increases in bone mineral density and, in the 70-79-year-old subgroup, in sexual desire, arousal, activity and satisfaction. The dose of 200 mg also proved to decrease disease activity in systemic lupus erythematosus. Lastly, high DHEA doses have improved mood in various groups of patients of any age and gender with depressive symptoms. The use of DHEA therapy may also be discussed in women of any age when a trial of androgen supplementation seems justified because of the existence of an inhibited sexual desire or a sexual arousal disorder associated with documented androgen deficiency. The rather weak conversion of DHEA into testosterone protects from the risk of overdosing associated with testosterone preparations. However, it must

  3. Dehydroepiandrosterone and age-related cognitive decline.

    Science.gov (United States)

    Sorwell, Krystina G; Urbanski, Henryk F

    2010-03-01

    In humans the circulating concentrations of dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS) decrease markedly during aging, and have been implicated in age-associated cognitive decline. This has led to the hypothesis that DHEA supplementation during aging may improve memory. In rodents, a cognitive anti-aging effect of DHEA and DHEAS has been observed but it is unclear whether this effect is mediated indirectly through conversion of these steroids to estradiol. Moreover, despite the demonstration of correlations between endogenous DHEA concentrations and cognitive ability in certain human patient populations, such correlations have yet to be convincingly demonstrated during normal human aging. This review highlights important differences between rodents and primates in terms of their circulating DHEA and DHEAS concentrations, and suggests that age-related changes within the human DHEA metabolic pathway may contribute to the relative inefficacy of DHEA replacement therapies in humans. The review also highlights the value of using nonhuman primates as a pragmatic animal model for testing the therapeutic potential of DHEA for age-associate cognitive decline in humans.

  4. Dehydroepiandrosterone administration in humans: evidence based?

    NARCIS (Netherlands)

    Bovenberg, S.; Uum, S.H.M. van; Hermus, A.R.M.M.

    2005-01-01

    Dehydroepiandrosterone (DHEA) and its ester dehydroepiandrosterone sulphate (DHEAS) are produced by the adrenal glands. These hormones are inactive precursors that are transformed into active sex steroids in peripheral target tissues. After a peak in early adulthood, there is a marked decrease in

  5. Dysregulation of Neurosteroids in Obsessive Compulsive Disorder

    OpenAIRE

    Bigos, KL; Folan, MM; Jones, Van; Haas, GL; Kroboth, FJ; Kroboth, PD

    2008-01-01

    Alterations in hormone concentrations, including adrenocorticotropin, corticotropin releasing hormone, and cortisol have been reported in patients with obsessive compulsive disorder (OCD). Dehydroepiandrosterone (DHEA) and its sulfated metabolite, DHEA-S, have not been assessed in patients with OCD. We report 24-hour serum DHEA, DHEA-S, and cortisol concentrations in a young man with OCD and 15 healthy young men. Circadian patterns of DHEA and cortisol were markedly different in the subject w...

  6. DHEA and mortality: what is the nature of the association?

    Science.gov (United States)

    Ohlsson, Claes; Vandenput, Liesbeth; Tivesten, Asa

    2015-01-01

    Although very little is known about the importance of dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEA-S) in human physiology and pathophysiology, emerging observations imply pivotal roles of DHEA/-S. One such observation is the association between serum DHEA/-S levels and mortality risk. In this review, we focus on the literature addressing DHEA/-S and mortality with the aim to describe and discuss patterns and potential underlying mechanisms. Although the literature reports somewhat inconsistent results, we conclude that several larger population-based studies support an association between low DHEA/-S and risk of death, at least in elderly men. In women, the association may not be present; alternatively, there may be a U-shaped association. In men, most available evidence suggests an association with cardiovascular (CV) mortality rather than cancer mortality. Further, there are biologically plausible mechanisms for an effect of DHEA/-S on the development of CV disease. On the other hand, there is also strong evidence supporting that any disease may lower DHEA/-S. Thus, the cause-effect relation of this association is less clear. Future studies may employ a mendelian randomization approach using genetic determinants of DHEA-S levels as predictors of clinical outcomes, to delineate the true nature of the association between DHEA/-S and mortality. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Trypanosoma cruzi: orchiectomy and dehydroepiandrosterone therapy in infected rats.

    Science.gov (United States)

    Filipin, Marina Del Vecchio; Brazão, Vânia; Caetano, Leony Cristina; Santello, Fabricia Helena; Toldo, Míriam Paula Alonso; Caetano, Luana Naiara; do Prado, José Clóvis

    2008-11-01

    The ability of gonadal hormones to influence and induce diverse immunological functions during the course of a number of parasitic infections has been extensively studied in the latest decades. Dehydroepiandrosterone and its sulfate are the most abundant steroid hormones secreted by the human adrenal cortex and are considered potent immune-activators. The effects of orchiectomy on the course of Trypanosoma cruzi infection in rats, treated and untreated with DHEA were examined, by comparing blood and cardiac parasitism, macrophage numbers, nitric oxide and IFN-gamma levels. Orchiectomy enhanced resistance against infection with elevated numbers of macrophages, enhanced concentrations of NO and IFN-gamma and reduced amastigote burdens in heart when compared to control animals. DHEA replacement exerted a synergistic effect, up-modulating the immune response. Male sex steroids appear to play fundamental role in determining the outcome of disease, through the regulation and modulation of the activity of the immune response.

  8. Dehydroepiandrosterone (DHEA) supplementation for cognitive function .

    Science.gov (United States)

    Huppert, F A; Van Niekerk, J K

    2001-01-01

    In view of the theoretical rationale for beneficial effects of DHEA and DHEAS on cognitive function in ageing and dementia, we have undertaken a thorough investigation of well-conducted studies in this area. This will provide a basis for confirmation of any effect of DHEA/S administration in humans in properly controlled trials. The review will also provide a scientific basis for effective dosage, acceptable route and duration of administration, and side effect profiles. This review is especially pertinent at this time as DHEA is currently being sold in large quantities in health food stores, particularly in the USA. In some cases the recommended dose is different for men and women (50mg/day for men and 25mg/day for women) and the basis for this recommendation needs to be explored. To establish whether administration of DHEA, or its sulphate, DHEAS, improves cognitive function or reduces the rate of decline of cognitive function in normal older adults or in individuals with dementia. Relevant electronic databases, journals, personal communications and conference abstracts were searched for randomised controlled trials investigating the effects of DHEA/S on cognition in older adults. All relevant randomised controlled trials of DHEA/S were considered for inclusion in the review. Data for the specified outcomes were independently extracted by two reviewers (FAH & JvN) and cross-checked. Any discrepancies were discussed and resolved. No data pooling was undertaken owing to the lack of availability of the relevant statistics. There are four included studies, three cognition in normal older people, and Barnhart 1999 in perimenopausal women with decreased well-being. There were no studies in dementia. There were a few significant findings. Wolf 1997 found significant improvement following DHEA compared with placebo in both immediate recall (MD 0.8, 95% CI 0.16, 1.44) and delayed recall (MD 0.9, 95% CI 0.09, 1.71) of a visual memory test in women, estimated in a crossover

  9. WITHDRAWN: Dehydroepiandrosterone (DHEA) supplementation for cognitive function.

    Science.gov (United States)

    Huppert, F A; Van Niekerk, J K

    2007-07-18

    In view of the theoretical rationale for beneficial effects of DHEA and DHEAS on cognitive function in ageing and dementia, we have undertaken a thorough investigation of well-conducted studies in this area. This will provide a basis for confirmation of any effect of DHEA/S administration in humans in properly controlled trials. The review will also provide a scientific basis for effective dosage, acceptable route and duration of administration, and side effect profiles. This review is especially pertinent at this time as DHEA is currently being sold in large quantities in health food stores, particularly in the USA. In some cases the recommended dose is different for men and women (50mg/day for men and 25mg/day for women) and the basis for this recommendation needs to be explored. To establish whether administration of DHEA, or its sulphate, DHEAS, improves cognitive function or reduces the rate of decline of cognitive function in normal older adults or in individuals with dementia. Relevant electronic databases, journals, personal communications and conference abstracts were searched for randomised controlled trials investigating the effects of DHEA/S on cognition in older adults. All relevant randomised controlled trials of DHEA/S were considered for inclusion in the review. Data for the specified outcomes were independently extracted by two reviewers (FAH & JvN) and cross-checked. Any discrepancies were discussed and resolved. No data pooling was undertaken owing to the lack of availability of the relevant statistics. There are four included studies, three cognition in normal older people, and Barnhart 1999 in perimenopausal women with decreased well-being. There were no studies in dementia. There were a few significant findings. Wolf 1997 found significant improvement following DHEA compared with placebo in both immediate recall (MD 0.8, 95% CI 0.16, 1.44) and delayed recall (MD 0.9, 95% CI 0.09, 1.71) of a visual memory test in women, estimated in a crossover

  10. Dehydroepiandrosterone levels and cognitive function in aging

    OpenAIRE

    Rathna Kumari U, Padma K

    2013-01-01

    Dehydroepiandrosterone (DHEA) is a steroid hormone secreted by the adrenal cortex. Recent research reports show that DHEA has various beneficial effects including neuro protective effects and that the decline in its production with aging may contribute to neuronal dysfunction and degeneration, and thus cognitive decline.Aim: To assess the cognitive functions and estimate the levels of DHEA in subjects of the same age group. Materials and Methods: A cross sectional comparative study of sixty h...

  11. Genetic linkage mapping of the dehydroepiandrosterone sulfotransferase (STD) gene on the chromosome 19q13.3 region

    Energy Technology Data Exchange (ETDEWEB)

    Durocher, F.; Morissette, J.; Dufort, I.; Simard, J.; Luu-The, V. [Laval Univ. Quebec (Canada)

    1995-10-10

    In the human liver and adrenal, there is a single hydroxysteroid sulfotransferase, which catalyzes the transformation of dehydroepiandrosterone to dehydroepiandrosterone sulfate, the most abundantly circulating steroid in humans, and also catalyzes the sulfation of a series of other 3{beta}-hydroxysteroids as well as cholesterol. Dehydroepiandrosterone sulfate serves as precursor for the formation of active androgens and estrogens in several peripheral tissues, indicating that hydroxysteroid sulfotransferase plays a pivotal role in controlling the hormonal action of sex steroids by regulating their bioavailability. We recently elucidated the structure of the gene encoding hydroxysteroid sulfotransferase (STD), also designated dehydroepiandrosterone sulfotransferase, which spans 17 kb and contains six exons. The STD gene was preliminarily assigned to chromosome 19 by polymerase chain reaction (PCR) amplification of DNA from a panel of human/rodent somatic cell hybrids. To locate the STD gene, the novel biallelic polymorphism found in intron 2 was genotyped in eight CEPH reference families by direct sequencing of PCR products. Two-point linkage analysis was first performed between the latter polymorphism and chromosome 19 markers from Genethon and NIH/CEPH. The closest linkage was observed with D19S412 (Z{sub max} = 9.23; {theta}{sub max} 0.038) and HRC (Z{sub max} =5.95; {theta}{sub max}0.036), located on the 19q13.3 region. A framework map including six Genethon markers flanking the polymorphic STD gene was created by multipoint linkage analysis. Thereafter, a high-resolution genetic map of the region was constructed, yielding to the following order: qter-D19S414-D19S224-D19S420-D19S217-(APOC2-D19S412)-(STD-HRC)-KLK-D19S22-D19S180-PRKCG-D19S418-tel. 24 refs., 2 figs.

  12. Dehydroepiandrosterone biosynthesis, metabolism, biological effects, and clinical use (analytical review

    Directory of Open Access Journals (Sweden)

    N. P. Goncharov

    2015-04-01

    Full Text Available The review presents the fundamental information on the metabolism of dehydroepiandrosterone (DHEA, its biological role and possibilities of its use for replacement therapy. There were studied species differences in the synthesis of DHEA in the adrenal cortex. It was found that DHEA and DHEA-sulfate are produced only by the adrenal glands of humans and monkeys, including lower monkeys. Their biosynthesis involves the following steps: cholesterol → pregnenolone → 17-hydroxypregnenolone → DHEA. The adrenal glands of other species, including rats and mice do not synthesize DHEA. At the same time, in certain brain structures not only in man and monkey, but also in other animals DHEA and its precursors are synthesized de novo which are denoted as neurosteroids. It was demonstrated that Purkinje cells which play an important role in memory formation and learning are mainly place neurosteroid formation in mammals and other vertebrates. To establish the relationship of age and the level of DHEA and other steroids we studied the dynamics of their levels at different periods of postnatal development of people. Peak concentration DHEA observed in aged 25–30 years. In the interval from 20 to 90 years in humans the level falls approximately for 90 %. Cortisol levels in blood does not vary with age, leading to an imbalance in the ratio of cortisol/DHEA. Proved a major role of DHEA as a source (precursor for the synthesis of biologically active sex steroids – testosterone, estradiol and estrone in peripheral tissues. This review presents the bioavailability of DHEA in various physiological and pathological processes in humans and animals. In animal experiments has shown a higher bioavailability of DHEA in transdermal administration as compared with oral administration as in this case there is no steroid rapid inactivation in the liver during its first passage. According to recent studies there is a pronounced dependence of bioavailability of DHEA

  13. Dehydroepiandrosterone biosynthesis, metabolism, biological effects, and clinical use (analytical review

    Directory of Open Access Journals (Sweden)

    N. P. Goncharov

    2015-01-01

    Full Text Available The review presents the fundamental information on the metabolism of dehydroepiandrosterone (DHEA, its biological role and possibilities of its use for replacement therapy. There were studied species differences in the synthesis of DHEA in the adrenal cortex. It was found that DHEA and DHEA-sulfate are produced only by the adrenal glands of humans and monkeys, including lower monkeys. Their biosynthesis involves the following steps: cholesterol → pregnenolone → 17-hydroxypregnenolone → DHEA. The adrenal glands of other species, including rats and mice do not synthesize DHEA. At the same time, in certain brain structures not only in man and monkey, but also in other animals DHEA and its precursors are synthesized de novo which are denoted as neurosteroids. It was demonstrated that Purkinje cells which play an important role in memory formation and learning are mainly place neurosteroid formation in mammals and other vertebrates. To establish the relationship of age and the level of DHEA and other steroids we studied the dynamics of their levels at different periods of postnatal development of people. Peak concentration DHEA observed in aged 25–30 years. In the interval from 20 to 90 years in humans the level falls approximately for 90 %. Cortisol levels in blood does not vary with age, leading to an imbalance in the ratio of cortisol/DHEA. Proved a major role of DHEA as a source (precursor for the synthesis of biologically active sex steroids – testosterone, estradiol and estrone in peripheral tissues. This review presents the bioavailability of DHEA in various physiological and pathological processes in humans and animals. In animal experiments has shown a higher bioavailability of DHEA in transdermal administration as compared with oral administration as in this case there is no steroid rapid inactivation in the liver during its first passage. According to recent studies there is a pronounced dependence of bioavailability of DHEA

  14. [Dehydroepiandrosterone(DHEA)and bone metabolism].

    Science.gov (United States)

    Ohnaka, Keizo

    2016-07-01

    Dehydroepiandrosterone(DHEA), an adrenal androgen, has attracted much attention as an anti-aging hormone as well as a marker for senescence because of its unique change along with aging. DHEA is reported to have beneficial effects such as anti-diabetes, anti-obesity, and anti-atherosclerosis. It is also shown that DHEA has anti-osteoporosis effects to increase bone mineral density in randomized controlled trials(RCTs). As osteoblasts express aromatase which will convert androgen to estrogen, DHEA may act protectively against osteoporosis through its metabolites. Because there is no report on fracture risk by DHEA administration, further studies are required to clarify DHEA effects on human bone metabolism.

  15. Asthma and dehydroepiandrosterone (DHEA): facts and hypotheses.

    Science.gov (United States)

    Kasperska-Zajac, Alicja

    2010-10-01

    Dehydroepiandrosterone (DHEA) is considered as an important immunomodulating and anti-inflammatory hormone. Despite the continuing interest in DHEA replacement therapy, our knowledge of its effects upon asthma is very limited. DHEA is able to reverse cytokine imbalances associated with asthma, may prevent and attenuate allergic inflammation in airways, and does not possess the undesirable side effects of glucocorticoids; therefore, it may be potentially applied in the treatment of asthma. The steroid-sparing effect observed with DHEA clinically could appear especially favorable in asthmatic patients receiving oral treatment and those inhaling high doses of glucocorticoids. In addition, DHEA and its analogs might prove useful in reversing relative glucocorticoids insensitivity in patients with corticosteroid-resistant asthma. In this review we have focused specifically on DHEA's role in asthma.

  16. Analysis of pregnenolone and dehydroepiandrosterone in rodent brain: cholesterol autoxidation is the key

    Science.gov (United States)

    Liere, Philippe; Pianos, Antoine; Eychenne, Bernard; Cambourg, Annie; Bodin, Karl; Griffiths, William; Schumacher, Michael; Baulieu, Etienne-Emile; Sjövall, Jan

    2009-01-01

    Pregnenolone (PREG) and dehydroepiandrosterone (DHEA), and their respective sulfated forms PREGS and DHEAS, were among the first steroids to be identified in rodent brain. However, unreliable steroid isolation and solvolysis procedures resulted in errors, particularly in the case of brain steroid sulfates analyzed by radioimmunology or GC-MS of liberated free steroids. By using a solid-phase extraction recycling/elution procedure, allowing the strict separation of sulfated, free, and fatty acid esters of PREG and DHEA, PREGS and DHEAS, unlike free PREG, were not detected in rat and mouse brain and plasma. Conversely, considerable amounts of PREG and DHEA were released from unknown precursor(s) present in the lipoidal fraction, distinct from fatty acid ester conjugates. Chromatographic and mass spectrometric studies of the nature of the precursor(s) showed that autoxidation of brain cholesterol (CHOL) was responsible for the release of PREG and DHEA from the lipoidal fraction. When inappropriate protocols were used, CHOL was also the precursor of PREG and DHEA obtained from the fraction assumed to contain sulfated steroids. In contrast, free PREG was definitely confirmed as an endogenous steroid in rat brain. Our study shows that an early removal of CHOL from brain extracts coupled to well-validated extraction and fractionation procedures are prerequisites for reliable measurements of free and conjugated PREG and DHEA by GC-MS or other indirect methods. PMID:19506304

  17. Bu-Shen-Ning-Xin decoction suppresses osteoclastogenesis via increasing dehydroepiandrosterone to prevent postmenopausal osteoporosis.

    Science.gov (United States)

    Gui, Yuyan; Qiu, Xuemin; Xu, Yingping; Li, Dajin; Wang, Ling

    2015-06-01

    Bu-Shen-Ning-Xin decoction (BSNXD), a traditional Chinese medicine, has been used to prevent and treat age-related diseases such as postmenopausal osteoporosis (PMO) for decades. This study sought to investigate the underlying mechanisms of BSNXD in terms of receptor activation of nuclear factor κB ligand (RANKL)-induced osteoclastogenesis in vitro because of the critical roles of bone resorption in the development and progression of osteoporosis. In mice, serum levels of dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), and 17-β-estradiol (E2) were evaluated with an enzyme immunoassay kit after ovariectomy. Levels of DHEA and DHEAS increased significantly following administration of BSNXD while the level of E2 did not. In addition, tartrate-resistance acid phosphatase staining showed that DHEA profoundly inhibited RANKL-induced osteoclastogenesis in vitro in a dose-dependent manner via estrogen receptor α (ERα) but not via estrogen receptor β or androgen receptors. Cytotoxicity was not detected in the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. These data suggest that BSNXD prevents PMO by increasing DHEA via the ERαpathway to suppress osteoclastogenesis.

  18. Protection of cumulus cells following dehydroepiandrosterone supplementation.

    Science.gov (United States)

    Lin, Li-Te; Wang, Peng-Hui; Chen, San-Nung; Li, Chia-Jung; Wen, Zhi-Hong; Cheng, Jiin-Tsuey; Tsui, Kuan-Hao

    2017-02-01

    Growing studies have demonstrated that dehydroepiandrosterone (DHEA) may improve fertility outcomes in poor ovarian responders (PORs). The aim of this study was to compare clinical outcomes and cumulus cell (CC) expression before and after DHEA treatment in PORs undergoing in vitro fertilization (IVF) cycles. Six patients with poor ovarian response were enrolled in the study according to Bologna criteria. DHEA was supplied at least 2 months before patients entered into the next IVF cycle. Expression of apoptosis-related genes in CCs was determined by quantitative real-time PCR. Mitochondrial dehydrogenase activity of CCs was assessed by cell counting kit-8 assay. Metaphase II oocytes, maturation rate, embryos at Day 3, and fertilization rate significantly increased following DHEA treatment. Expression of cytochrome c, caspase 9, and caspase 3 genes in CCs were significantly reduced after DHEA therapy. Additionally, increased mitochondrial activity of CCs was observed following DHEA supplementation. DHEA supplementation may protect CCs via improved mitochondrial activity and decreased apoptosis, leading to better clinical outcomes in PORs.

  19. Dehydroepiandrosterone levels and cognitive function in aging

    Directory of Open Access Journals (Sweden)

    Rathna Kumari U, Padma K

    2013-01-01

    Full Text Available Dehydroepiandrosterone (DHEA is a steroid hormone secreted by the adrenal cortex. Recent research reports show that DHEA has various beneficial effects including neuro protective effects and that the decline in its production with aging may contribute to neuronal dysfunction and degeneration, and thus cognitive decline.Aim: To assess the cognitive functions and estimate the levels of DHEA in subjects of the same age group. Materials and Methods: A cross sectional comparative study of sixty healthy male participants between 60 to 70 years of age was done. They did not have other medical disorders likely to affect cognitive function. Their performance in the principal domains of cognition, i.e. memory, attention and concentration, verbal fluency, language and visuospatial functioning was observed.Serum levels of DHEA were estimated for all the participants by ELISA method. Results: A significant positive correlation was observed between DHEA level and three domains of cognition viz., visuospatial skills (r = 0.95, verbal fluency (r = 0.49 and short term memory (r = 0.28. No association was found with other domains of cognition. Conclusion: Subjects with low levels of serum DHEA among the same age group showed a significant decline in visuospatial skills, short term memory and verbal fluency.

  20. Cholesterol sulfate in human physiology: what's it all about?

    Science.gov (United States)

    Strott, Charles A; Higashi, Yuko

    2003-07-01

    Cholesterol sulfate is quantitatively the most important known sterol sulfate in human plasma, where it is present in a concentration that overlaps that of the other abundant circulating steroid sulfate, dehydroepiandrosterone (DHEA) sulfate. Although these sulfolipids have similar production and metabolic clearance rates, they arise from distinct sources and are metabolized by different pathways. While the function of DHEA sulfate remains an enigma, cholesterol sulfate has emerged as an important regulatory molecule. Cholesterol sulfate is a component of cell membranes where it has a stabilizing role, e.g., protecting erythrocytes from osmotic lysis and regulating sperm capacitation. It is present in platelet membranes where it supports platelet adhesion. Cholesterol sulfate can regulate the activity of serine proteases, e.g., those involved in blood clotting, fibrinolysis, and epidermal cell adhesion. As a result of its ability to regulate the activity of selective protein kinase C isoforms and modulate the specificity of phosphatidylinositol 3-kinase, cholesterol sulfate is involved in signal transduction. Cholesterol sulfate functions in keratinocyte differentiation, inducing genes that encode for key components involved in development of the barrier. The accumulating evidence demonstrating a regulatory function for cholesterol sulfate appears solid; the challenge now is to work out the molecular mechanisms whereby this interesting molecule carries out its various roles.

  1. Immunohistochemical analysis of a novel dehydroepiandrosterone sulfotransferase-like protein in Drosophila neural circuits.

    Science.gov (United States)

    Liu, Tzu-An; Liu, Ming-Cheh; Yang, Yuh-Shyong

    2008-02-29

    Sulfotransferase (ST)-catalyzed sulfation plays an important role in various neuronal functions such as homeostasis of catecholamine neurotransmitters and hormones. Drosophila is a popular model for the study of memory and behavioral manifestations because it is able to mimic the intricate neuroregulation and recognition in humans. However, there has been no evidence indicating that cytosolic ST(s) is(are) present in Drosophila. The aim of this study is to investigate whether or not cytosolic ST(s) is(are) expressed in the Drosophila nervous system. Immunoblot analysis demonstrated the presence of dehydroepiandrosterone (DHEA) ST-like protein in Drosophila brain and a sensitive fluorometric assay revealed its sulfating activity toward DHEA. Immunohistochemical staining demonstrated this DHEA ST-like protein to be abundant in specific neurons as well as in several bundles of nerve fibers in Drosophila. Clarification of a possible link between ST and a neurotransmitter-mediated effect may eventually aid in designing approaches for alleviating neuronal disorders in humans.

  2. Dehydroepiandrosterone (DHEA) substitution treatment for severe fatigue in DHEA-deficient patients with primary Sjögren's syndrome.

    Science.gov (United States)

    Virkki, Liisa M; Porola, Pauliina; Forsblad-d'Elia, Helena; Valtysdottir, Sigridur; Solovieva, Svetlana A; Konttinen, Yrjö T

    2010-01-15

    Primary Sjögren's syndrome (SS) is characterized by fatigue and low levels of serum dehydroepiandrosterone/dehydroepiandrosterone sulfate (DHEA/DHEAS). Our aim was to study whether SS patients with severe fatigue and low serum DHEAS values benefit from DHEA substitution (50 mg/day). A multicenter, investigator-based, powered, randomized controlled clinical trial (crossover, washout design) using fatigue as the primary outcome measure was performed on patients with primary SS (n = 107) who had a general fatigue score > or =14 on the 20-item Multiple Fatigue Inventory (MFI-20), combined with age- and sex-adjusted serum DHEAS values below the mean. Fatigue was assessed using MFI-20 subscales, i.e., general fatigue, physical fatigue, mental fatigue, reduced motivation, and activity (scale 4-20), and with a visual analog scale (VAS; scale 0-100). In an intent-to-treat analysis, a 50-mg DHEA substitution dose and placebo similarly improved fatigue. All of the MFI-20 subscales and the fatigue VAS improved from the baseline levels as a result of treatment (P DHEA in DHEA-deficient and severely tired primary SS patients does not help against fatigue better than placebo. This may relate to the prohormone nature of DHEA and its recently described defective intracrine tissue-specific conversion to active sex steroids in SS.

  3. Dehydroepiandrosterone sulphate: action and mechanism in the brain.

    Science.gov (United States)

    Dong, Y; Zheng, P

    2012-01-01

    Dehydroepiandrosterone sulphate (DHEAS) is synthesised from dehydroepiandrosterone by the enzyme sulphotransferase. DHEAS is one of the most important neurosteroids in the brain. The concentration of DHEAS in the brain is sometimes higher than peripheral system. At the cellular level, DHEAS has been shown to modulate a variety of synaptic transmission, including cholinergic, GABAergic dopaminergic and glutamatergic synaptic transmission. In addition to the effect on the release of a number of neurotransmitters, DHEAS could also modulate the activity of postsynaptic receptors. DHEAS has been found to have multiple important effects on brain functions, such as memory enhancing, antidepressant and anxiolytic effects, and may have relationships with many brain diseases. © 2011 The Authors. Journal of Neuroendocrinology © 2011 Blackwell Publishing Ltd.

  4. DHEA, physical exercise and doping.

    Science.gov (United States)

    Collomp, K; Buisson, C; Lasne, F; Collomp, R

    2015-01-01

    The dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEA-S) concentrations during acute and chronic exercise (training) have been investigated only fairly recently. DHEA is generally preferred to DHEA-S for exploring the acute exercise repercussions in laboratory or field tests because of its shorter elimination half-life. Conversely, DHEA-S is preferred to estimate chronic adaptations. Both can be measured noninvasively in saliva, and it is therefore possible to follow these hormone responses in elite athletes during competitive events and in healthy and pathological populations, without imposing additional stress. Indeed, the correlation between saliva and serum concentrations is high for steroid hormones, both at rest and during exercise. In this review, we will first summarize the current knowledge on the DHEA/DHEA-S responses to exercise and examine the potential modulating factors: exercise intensity, gender, age, and training. We will then discuss the ergogenic effects that athletes expect from the exogenous administration of DHEA and the antidoping methods of analysis currently used to detect this abuse. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Dehydroepiandrosterone inhibits lipopolysaccharide-induced nitric oxide production in BV-2 microglia.

    Science.gov (United States)

    Wang, M J; Huang, H M; Chen, H L; Kuo, J S; Jeng, K C

    2001-05-01

    Levels of dehydroepiandrosterone (DHEA) and its sulfated derivative (DHEAS) decline during aging and reach even lower levels in Alzheimer's disease (AD). DHEA is known to exhibit a variety of functional activities in the CNS, including an increase of memory and learning, neurotrophic and neuroprotective effects, and the reduction of risk of age-related neurodegenerative disorders. However, the influence of DHEA on the immune functions of glial cells is poorly understood. In this study, we investigated the effect of DHEA on activated glia. The production of inducible nitric oxide synthase (iNOS) was studied in lipopolysaccharide (LPS)-stimulated BV-2 microglia, as a model of glial activation. The results showed that DHEA but not DHEAS significantly inhibited the production of nitrite in the LPS-stimulated BV-2 cell cultures. Pretreatment of BV-2 cells with DHEA reduced the LPS-induced iNOS mRNA and protein levels in a dose-dependent manner. The LPS-induced iNOS activity in BV-2 cells was decreased by the exposure of 100 microM DHEA. Moreover, DHEA suppressed iNOS gene expression in LPS-stimulated BV-2 cells did not require de novo synthesis of new proteins or destabilize of iNOS mRNA. Since DHEA is biosynthesized by astrocytes and neurons, our findings suggest that it might have an important regulatory function on microglia.

  6. Neurobiological and neuropsychiatric effects of dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS).

    Science.gov (United States)

    Maninger, Nicole; Wolkowitz, Owen M; Reus, Victor I; Epel, Elissa S; Mellon, Synthia H

    2009-01-01

    DHEA and DHEAS are steroids synthesized in human adrenals, but their function is unclear. In addition to adrenal synthesis, evidence also indicates that DHEA and DHEAS are synthesized in the brain, further suggesting a role of these hormones in brain function and development. Despite intensifying research into the biology of DHEA and DHEAS, many questions concerning their mechanisms of action and their potential involvement in neuropsychiatric illnesses remain unanswered. We review and distill the preclinical and clinical data on DHEA and DHEAS, focusing on (i) biological actions and putative mechanisms of action, (ii) differences in endogenous circulating concentrations in normal subjects and patients with neuropsychiatric diseases, and (iii) the therapeutic potential of DHEA in treating these conditions. Biological actions of DHEA and DHEAS include neuroprotection, neurite growth, and antagonistic effects on oxidants and glucocorticoids. Accumulating data suggest abnormal DHEA and/or DHEAS concentrations in several neuropsychiatric conditions. The evidence that DHEA and DHEAS may be fruitful targets for pharmacotherapy in some conditions is reviewed.

  7. Salivary cortisol and dehydroepiandrosterone sulfate in adolescent rape victims with post traumatic stress disorder

    NARCIS (Netherlands)

    Bicanic, Iva A. E.; Postma, Riemke M.; Sinnema, Gerben; De Roos, Carlijn; Olff, Miranda; Van Wesel, Floryt; Van de Putte, Elise M.

    2013-01-01

    Background: In chronic sexual abuse victims with post traumatic stress disorder (PTSD), the hypothalamic pituitary adrenal (HPA) axis can be dysregulated. In single rape victims, PTSD symptoms are hypothesized to function as a chronic stressor leading to similar HPA-axis dysregulation. The objective

  8. Salivary cortisol and dehydroepiandrosterone sulfate in adolescent rape victims with post traumatic stress disorder

    NARCIS (Netherlands)

    Bicanic, Iva A. E.; Postma, Riemke M.; Sinnema, Gerben; De Roos, Carlijn; Olff, Miranda; Van Wesel, Floryt; Van de Putte, Elise M.

    2013-01-01

    Background: In chronic sexual abuse victims with post traumatic stress disorder (PTSD), the hypothalamic pituitary adrenal (HPA) axis can be dysregulated. In single rape victims, PTSD symptoms are hypothesized to function as a chronic stressor leading to similar HPA-axis dysregulation. The objective

  9. Disposition and metabolic profile of the weak androgen Dehydroepiandrosterone (DHEA) following administration as part of a nutritional supplement to exercised horses.

    Science.gov (United States)

    Knych, H K; Arthur, R M; Stanley, S D; McKemie, D S

    2015-01-01

    In order to ensure the welfare of performance horses and riders as well as the integrity of the sport, the use of both therapeutic and illegal agents in horse racing is tightly regulated. While Dehydroepiandrosterone (DHEA) is not specifically banned from administration to racehorses in the United States and no screening limit or threshold concentration exists, the metabolic conversion of DHEA to testosterone make its presence in nutritional supplements a regulatory concern. The recommended regulatory threshold for total testosterone in urine is 55 and 20 ng/mL for mares and geldings, respectively. In plasma, screening and confirmation limits for free testosterone (mares and geldings), of no greater than 0.1 and 0.025 ng/mL, respectively are recommended. DHEA was administered orally, as part of a nutritional supplement, to 8 exercised female thoroughbred horses and plasma and urine samples collected at pre-determined times post administration. Using liquid chromatography-mass spectrometry (LC-MS), plasma and urine samples were analyzed for DHEA, DHEA-sulfate, testosterone, testosterone-sulfate, pregnenolone, androstenedione, and androstenediol. DHEA was rapidly absorbed with maximal plasma concentrations reaching 52.0 ± 43.8 ng/mL and 32.1 ± 12.9 ng/mL for DHEA and DHEA sulfate, respectively. Free testosterone was not detected in plasma or urine samples at any time. Maximum sulfate conjugated testosterone plasma concentrations were 0.98 ± 1.09 ng/mL. Plasma testosterone-sulfate concentrations did not fall below 0.1 ng/mL and urine testosterone-sulfate below 55 ng/mL until 24-36 h post DHEA administration. Urine testosterone sulfate concentrations remained slightly above baseline levels at 48 h for most of the horses studied. Copyright © 2014 John Wiley & Sons, Ltd.

  10. Dehydroepiandrosterone (DHEA) inhibits voltage-gated T-type calcium channels.

    Science.gov (United States)

    Chevalier, M; Gilbert, G; Lory, P; Marthan, R; Quignard, J F; Savineau, J P

    2012-06-01

    Dehydroepiandrosterone (DHEA) and its sulfated form, DHEAS, are the most abundant steroid hormones in the mammalian blood flow. DHEA may have beneficial effects in various pathophysiological conditions such as cardiovascular diseases or deterioration of the sense of well-being. However to date, the cellular mechanism underlying DHEA action remains elusive and may involve ion channel modulation. In this study, we have characterized the effect of DHEA on T-type voltage-activated calcium channels (T-channels), which are involved in several cardiovascular and neuronal diseases. Using the whole-cell patch-clamp technique, we demonstrate that DHEA inhibits the three recombinant T-channels (Ca(V)3.1, Ca(V)3.2 and Ca(V)3.3) expressed in NG108-15 cell line, as well as native T-channels in pulmonary artery smooth muscle cells. This effect of DHEA is both concentration (IC(50) between 2 and 7μM) and voltage-dependent and results in a significant shift of the steady-state inactivation curves toward hyperpolarized potentials. Consequently, DHEA reduces window T-current and inhibits membrane potential oscillations induced by Ca(V)3 channels. DHEA inhibition is not dependent on the activation of nuclear androgen or estrogen receptors and implicates a PTX-sensitive Gi protein pathway. Functionally, DHEA and the T-type inhibitor NNC 55-0396 inhibited KCl-induced contraction of pulmonary artery rings and their effect was not cumulative. Altogether, the present data demonstrate that DHEA inhibits T-channels by a Gi protein dependent pathway. DHEA-induced alteration in T-channel activity could thus account for its therapeutic action and/or physiological effects. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. Oral dehydroepiandrosterone (DHEA) replacement in older adults: effects on central adiposity, glucose metabolism, and blood lipids

    Science.gov (United States)

    Jankowski, Catherine M.; Gozansky, Wendolyn S.; Van Pelt, Rachael E.; Wolfe, Pamela; Schwartz, Robert S.; Kohrt, Wendy M.

    2011-01-01

    Objective The aim was to determine the effects of dehydroepiandrosterone (DHEA) therapy on changes in central adiposity, insulin action, and blood lipids. Many of the actions of DHEA in humans are thought to be mediated through its conversion to sex hormones, which are modulators of adiposity, muscularity, and insulin sensitivity. The effects of DHEA replacement on regional tissue composition, glucose metabolism, and blood lipid profile in older adults have been inconsistent. Design a randomized, double-blinded, placebo-controlled trial. The intervention was oral DHEA 50 mg/d or placebo for 12 months. Participants 58 women and 61 men, aged 60–88 yr, with low serum DHEA sulfate (DHEAS) levels at study entry. Measurements Computed tomography measures of abdominal fat areas, thigh muscle and fat areas, DXA-derived trunk fat mass, serum glucose and insulin responses to an oral glucose challenge, and fasted serum total cholesterol, HDL-cholesterol, LDL-cholesterol, and triglycerides were assessed before and after the intervention. Results There were no significant (P > 0.05) differences between the DHEA and placebo groups in the changes in regional tissue composition or glucose metabolism. HDL-cholesterol (P =0.01) and fasted triglycerides (P =0.02) decreased in women and men taking DHEA. Conclusion Restoring serum DHEAS levels in older adults to young adult levels for 1 year does not appear to reduce central adiposity or improve insulin action. The benefit of DHEA on decreasing serum triglycerides must be weighed against the HDL-lowering effect. PMID:21521341

  12. Dehydroepiandrosterone (DHEA) restrains intestinal inflammation by rendering leukocytes hyporesponsive and balancing colitogenic inflammatory responses.

    Science.gov (United States)

    Alves, Vanessa Beatriz Freitas; Basso, Paulo José; Nardini, Viviani; Silva, Angélica; Chica, Javier Emílio Lazo; Cardoso, Cristina Ribeiro de Barros

    2016-09-01

    Dehydroepiandrosterone (DHEA) is a hormone that plays an important role in the modulation of inflammatory responses. However, the precise mechanisms that link the actions of this androgen with protection or susceptibility to inflammatory bowel diseases (IBD) remain uknown. Here we showed that low dose DHEA inhibited proliferation of spleen cells and IFN-у production. The hormone was not toxic to myeloid lineage cells, although it caused necrosis of spleen cells at the intermediate and highest doses in vitro (50 and 100μM). The treatment of C57BL/6 mice with DHEA during colitis induction by dextran sodium sulfate (DSS) led to a reduction in weight loss and clinical signs of disease. There were decreased peripheral blood monocytes on day 6 of DSS exposure and treatment, besides increase in circulating neutrophils in the tissue repair phase. DHEA also led to reduced lamina propria cellularity and restoration of normal colon length. These results were accompanied by decreased expression of IL-6 and TGF-β mRNA, while IL-13 was augmented in the colon on day 6, which was probably related to attenuation of inflammation. There was retention of CD4(+) cells in the spleen after use of DHEA, along with augmented frequency of CD4(+)IL-4(+) cells, decreased CD4(+)IFN-ɣ(+) in spleen and constrained CD4(+)IL-17(+) population in the mesenteric lymph nodes. Moreover, splenocytes of mice treated with DHEA became hyporesponsive, as observed by reduced proliferation after re-stimulation ex-vivo. In conclusion, DHEA modifyies leukocyte activity and balances the exacerbated immune responses which drive local and systemic damages in IBD. Copyright © 2016 Elsevier GmbH. All rights reserved.

  13. Androgenic and estrogenic metabolites in serum of mice fed dehydroepiandrosterone: relationship to antihyperglycemic effects.

    Science.gov (United States)

    Leiter, E H; Beamer, W G; Coleman, D L; Longcope, C

    1987-09-01

    The steroid prehormone, dehydroepiandrosterone (DHEA) has potent antihyperglycemic effects when fed in the diet of genetically diabetic C57BL/KsJ-db/db mice. The purpose of this investigation was to analyze changes in sex steroid levels in serum of mice fed DHEA, and to compare the antihyperglycemic potencies of the various metabolites in order to clarify the mechanism of DHEA action. Steroid radioimmunoassays showed that dietary DHEA entered the blood in high concentrations and was actively metabolized to both androgens (testosterone, T; dihydrotestosterone, DHT) and estrogens (estrone, E1; 17 beta-estradiol, E2). This metabolism did not require intact adrenal glands or gonads. In C57BL/KsJ normal (+/+) males, conversion of DHEA to androgens was the prominent feature; in db/db males, DHEA feeding not only increased serum T and DHT, but also serum E1 and E2 levels. The db/db mice had increased amounts of adipose tissue that sequestered more intravenously injected 3H-E2; this additional body fat could account for increased aromatization of DHEA-derived estrogen precursors. Comparisons of the relative antihyperglycemic potencies of androgenic and estrogenic steroid metabolites of DHEA in db/db mice showed that the estrogens and metabolites with estrogenic properties (androstenediol) or those convertible to estrogens (DHEA sulfate) were the most potent. Although 17 beta-E2 was effective by injection or per os, DHEA was effective only when administered per os, implicating alimentary tract conversion of DHEA to more biologically active reactants. Based on the pivotal position of DHEA as a prehormone for androgens, estrogens, and etiocholanolones, an explanation of the seemingly paradoxical effects exerted by this compound in blocking autoimmune disease, hyperglycemia, obesity, and neoplasia was proposed.

  14. Photo-DHEA--a functional photoreactive dehydroepiandrosterone (DHEA) analog.

    Science.gov (United States)

    Waschatko, Gustav; Kojro, Elzbieta; Zahnow, Michael; Gehrig-Burger, Katja

    2011-04-01

    The steroid hormone dehydroepiandrosterone (DHEA) has beneficial effects on vascular function, survival of neurons, and fatty acid metabolism. However, a specific receptor for DHEA has not been identified to date. Here, we describe the synthesis of a photoreactive DHEA derivative (Photo-DHEA). In Photo-DHEA, typical characteristics of DHEA are conserved: (i) a "planar" tetracyclic ring system with a Δ(5) double bond, (ii) a 3β-hydroxyl group, and (iii) a keto group at C17. In cell-based assays, Photo-DHEA showed the same properties as DHEA. We conclude that Photo-DHEA is suitable for radioiodination to yield a tool for the identification of the elusive DHEA receptor. Copyright © 2011 Elsevier Inc. All rights reserved.

  15. [Functions and mechanisms of dehydroepiandrosterone in nervous system].

    Science.gov (United States)

    Xie, Li; Sun, Hui-Ying; Gao, Jing; Liao, Hong

    2006-10-01

    Dehydroepiandrosterone is the precursor of sex hormone, and can be synthesized in the brain de novo, which means it is a kind of neurosteroid. Animal experiments and clinical researches have proved that DHEA exhibits a variety of functional activities in the nervous system, including neurotrophic, neuroprotective effects and enhancement' of learning and memory, which suggests that it may be useful in preventing and treating some neural diseases such as neurodegenerative diseases, cerebral ischemia, trauma, psychosis and so on. The mechanisms of the effect of DHEA on protection against oxidative stress, excitotoxicity, apoptosis etc. were found to be through both genomic and nongenomic way. These effects and mechanisms in nervous system were summarized in the present paper.

  16. The Relationship Between Dehydroepiandrosterone (DHEA), Working Memory and Distraction - a Behavioral and Electrophysiological Approach

    OpenAIRE

    Sónia do Vale; Lenka Selinger; João Martin Martins; Ana Coelho Gomes; Manuel Bicho; Isabel do Carmo; Carles Escera

    2014-01-01

    Dehydroepiandrosterone (DHEA) and dehydroepiandrosterone-sulphate (DHEAS) have been reported to have memory enhancement effects in humans. A neuro-stimulatory action and an anti-cortisol mechanism of action may contribute to that relation. In order to study DHEA, DHEAS and cortisol relations to working memory and distraction, we recorded the electroencephalogram of 23 young women performing a discrimination (no working memory load) or 1-back (working memory load) task in an audio-visual oddba...

  17. [Dehydroepiandrosterone (DHEA)--structure, clinical importance and the role in human body].

    Science.gov (United States)

    Zdrojewicz, Z; Ciszko, B

    2001-01-01

    DHEA and DHEA-S are hormones synthetized primarily by the adrenal cortex. The levels oh this hormones are systematically decreased, beginning from the fourth life decade. The levels of this hormones are also abberrated as a consequence of divorce systematical diseases like cardiovascular diseases, skeletal diseases, diabetes mellitus or obesity. This hormones, probably, have antiaheromatic facilities. There are also data suggesting their influence on stimulation of immunological system. It is already confirmed that the levels of this hormones are modified in congenital function disorders that are present in different diseases, like Alzheimer diseases, and oral administration of DHEA can improves the memory. Presumably DHEA-S have also anticarcinogenic facilities. The levels of this hormones can be also a marker monitoring the course of pregnancy. There are still a lot of discrepancies between results of different studies and it is very difficult to describe their role in human body. Because their levels are decreased with ageing process, this observation makes the researchers call them as the "youth hormones".

  18. Sulfate inhibition effect on sulfate reducing bacteria

    Directory of Open Access Journals (Sweden)

    Sulaiman Al Zuhair

    2008-12-01

    Full Text Available There is an increasing interest in the potential of bacterial sulfate reduction as an alternative method for sulfate removal from wastewater. Under anaerobic conditions, sulfate-reducing bacteria (SRB utilize sulfate to oxidize organic compounds and generate sulfide (S2-. SRB were successfully isolated from sludge samples obtained from a local petroleum refinery, and used for sulfate removal. The effects of initial sulfate concentration, temperature and pH on the rate of bacterial growth and anaerobic sulfate removal were investigated and the optimum conditions were identified. The experimental data were used to determine the parameters of two proposed kinetic model, which take into consideration substrate inhibition effect. Keywords: Sulfate Reducing Bacteria, Sulfate, Kinetic Model, Biotreatement, Inhibition Received: 31 August 2008 / Received in revised form: 18 September 2008, Accepted: 18 September 2008 Published online: 28 September 2008

  19. Enzymic synthesis of steroid sulfates XVI. Specificity and regulation of human adrenal hydroxysteroid sulfotransferase.

    Science.gov (United States)

    Adams, J B; McDonald, D

    1983-05-01

    Pure hydroxysteroid sulfotransferase (EC 2.8.2.2) of human adrenal glands possesses a wide substrate specificity towards steroids. This wide specificity has now been found to extend to simple alcohols; normal aliphatic alcohols from C3 onwards acting as substrates with C9 showing the highest rate. Increased rate was accompanied by a decrease in Km. In marked contrast to the sulfurylation of steroids such as dehydroepiandrosterone, which exhibit wave-like kinetics, the kinetics with simple alcohols were of the normal Michaelis-Menten type. By means of enzyme antibody and enzyme stability studies evidence was provided that one and the same enzyme was responsible for sulfurylation of hydroxyls on the 3- and 17- positions of steroids and simple alcohols. The data lend support to previous evidence that the enzyme controls the secretion of dehydroepiandrosterone sulfate via steroid-specific binding sites, enabling self-regulation in response to ACTH action.

  20. Dehydroepiandrosterone (DHEA) supplementation for cognition and well-being.

    Science.gov (United States)

    Huppert, F A; Van Niekerk, J K; Herbert, J

    2000-01-01

    In view of the theoretical rationale for beneficial effects of DHEA and DHEAS in aging and dementia, we believe it is timely to undertake a thorough investigation of well-conducted studies in this area. This will provide a basis for confirmation of any effect of DHEA/S administration in humans, in large-scale and properly controlled trials, which would evaluate effective dosage, acceptable route and duration of administration and side effect profiles. This is especially pertinent at this time as DHEA is currently being sold in large quantities in health food stores, particularly in the USA. In some cases the recommended dose is different for men and women (50mg/day for men and 25mg/day for women) and the basis for this recommendation needs to be explored. To establish whether administration of DHEA, or its sulphate, DHEAS, improves psychological well-being and/or improves cognitive function or reduces the rate of decline of cognitive function in older adults or in individuals with dementia. All available electronic databases, hand searched journals, personal communications and conference abstracts were searched for randomised controlled trials of DHEA in well-being and cognition. The total yield from searching was 415 and the detailed breakdown is given in the body of this review. All relevant randomised controlled trials of DHEA or DHEAS were considered for inclusion in the review. Studies where groups are matched, rather than randomised, were also considered. Data for the specified outcomes were independently extracted by two reviewers (FAH & JvN) and cross-checked. Any discrepancies were discussed and resolved. Where possible and appropriate, data were pooled and the mean differences estimated. The published DHEA trials fall into 2 categories: 1. four German studies in which DHEA was administered for a period of two weeks or less; 2. a USA study in which DHEA was administered for three months. Well-being was assessed in both sets of studies and a significant

  1. Relationship between hyperandrogenism, obesity, inflammation and polycystic ovary syndrome.

    Science.gov (United States)

    Nehir Aytan, Asli; Bastu, Ercan; Demiral, Irem; Bulut, Huri; Dogan, Murat; Buyru, Faruk

    2016-09-01

    This prospective study aimed to determine the status of circulating levels of C-reactive protein (CRP), tumor necrosis factor α (TNF-α), IL-27, IL-35, IL-37, α-1 acid glycoprotein in patients with polycystic ovary syndrome (PCOS) compared with controls and to evaluate their relation with hyperandrogenism and obesity. Forty-eight patients with PCOS (29 obese, 19 lean) and 40 healthy controls (20 obese, 20 lean) were enrolled. CRP, TNF-α, IL-27, IL-35, IL-37, α-1 acid glycoprotein, sex hormone-binding globulin (SHBG), dehydroepiandrosterone sulfate (DHEA-S) levels were measured. Levels of total testosterone, A4, DHEA-S were significantly higher in patients with PCOS than in controls both in the obese and lean groups, while levels of SHBG were significantly lower in all patients with PCOS than in all (p obesity along with PCOS significantly elevates the inflammatory status and hyperandrogenism.

  2. Dehydroepiandrosterone increases resistance to experimental infection by Trypanosoma cruzi.

    Science.gov (United States)

    Santos, Carla Domingues; Toldo, Míriam Paula Alonso; Santello, Fabrícia Helena; Filipin, Marina Del Vecchio; Brazão, Vânia; do Prado Júnior, José Clóvis

    2008-05-31

    Dehydroepiandrosterone (DHEA) enhances immune responses against a wide range of viral, bacterial, and parasitic pathogens. In a previous study, we reported that administration of DHEA significantly decreased the numbers of blood parasites in Trypanosoma cruzi experimental infection. The present study was undertaken to determine the effectiveness of DHEA in reducing the severity of acute phase T. cruzi infection of male and female Wistar rats. Animals were treated subcutaneously with 40 mg/kg body weight/day of DHEA. The concentration of nitric oxide (NO) was determined in spleen peritoneal cavity. Interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) were determined in the sera of uninfected and infected animals. DHEA treatment augments NO production for both sexes after in vitro LPS treatment for uninfected animals. Infection triggered enhanced NO levels although not significant. IL-2 and IFN-gamma were detectable in higher concentrations in treated and infected rats of both genders when compared to untreated controls. These data suggest that DHEA may have a potent immunoregulatory function that can affect the course of T. cruzi infection.

  3. Dehydroepiandrosterone for the treatment of systemic lupus erythematosus.

    Science.gov (United States)

    van Vollenhoven, Ronald F

    2002-01-01

    The adrenal steroidal hormone dehydroepiandrosterone (DHEA) has been studied as a potential pharmacological agent in the treatment of the autoimmune disease systemic lupus erythematosus (SLE). Both the endocrine effects (the ability to be converted peripherally to androgenic and oestrogenic sex steroids) and the immunomodulatory effects of DHEA (the production of the Th(1) cytokines, such as IL-2) suggest that this hormone could be of benefit for patients with SLE. During the past decade, five controlled clinical trials and a number of additional observational studies have been performed investigating these possibilities. The results from these studies suggest that 200 mg/day of DHEA for 7 - 12 months decreases corticosteroid requirement for the patients, the frequency of disease flares, has an anti-osteoporotic effect and has an overall beneficial effect on SLE disease activity in female patients. A small study suggested benefits for cognitive function in such patients. The side effects acne and hirsutism were seen relatively frequently (30 - 40% and 10 - 12% of patients, respectively) but in most instances were deemed mild. DHEA treatment resulted in changes in lipid profile and may have endocrine effects, the consequences of which will need to be ascertained through longer-term follow-up studies.

  4. Dehydroepiandrosterone (DHEA) supplementation in diminished ovarian reserve (DOR).

    Science.gov (United States)

    Gleicher, Norbert; Barad, David H

    2011-05-17

    With infertility populations in the developed world rapidly aging, treatment of diminished ovarian reserve (DOR) assumes increasing clinical importance. Dehydroepiandrosterone (DHEA) has been reported to improve pregnancy chances with DOR, and is now utilized by approximately one third of all IVF centers world-wide. Increasing DHEA utilization and publication of a first prospectively randomized trial now warrants a systematic review. PubMed, Cochrane and Ovid Medline were searched between 1995 and 2010 under the following strategy: [DHEA or androgens or testosterone > and ]. Bibliographies of relevant publications were further explored for additional relevant citations. Since only one randomized study has been published, publications, independent of evidence levels and quality assessment, were reviewed. Current best available evidence suggests that DHEA improves ovarian function, increases pregnancy chances and, by reducing aneuploidy, lowers miscarriage rates. DHEA over time also appears to objectively improve ovarian reserve. Recent animal data support androgens in promoting preantral follicle growth and reduction in follicle atresia. Improvement of oocyte/embryo quality with DHEA supplementation potentially suggests a new concept of ovarian aging, where ovarian environments, but not oocytes themselves, age. DHEA may, thus, represent a first agent beneficially affecting aging ovarian environments. Others can be expected to follow.

  5. Behavioral effects of dehydroepiandrosterone in adult male rats.

    Science.gov (United States)

    Fedotova, Julia; Sapronov, Nikolay

    2004-09-01

    It is well-documented that dehydroepiandrosterone (DHEA) exhibits various behavioral effects in rodents, at least one of which is modulation of learning/memory processes in several test paradigms. However, little is known about the influence of DHEA on cognitive performance in the adult rodents. This work was designed to determine whether chronic DHEA administration during 10 days in the high (0.7 mg/kg, s.c.) or low (0.1 mg/kg, s.c.) doses has any effect on learning/memory abilities and behavior in the adult male rats (5- to 6-month old). Effect of DHEA was estimated in active and passive avoidance tasks, behavior was registered in the elevated "plus" maze and the "open field" test. DHEA in the high dose significantly (pDHEA in the low dose significantly (pDHEA in the high dose did not significantly modify behavior in intact rats as compared with control group. Results of the ANOVA on passive avoidance performance revealed no statistically significant differences among the groups receiving DHEA in the high or low doses as compared to the control. However, DHEA in the low dose significantly (pDHEA, the active avoidance performance did not differ significantly from the control. Thus, chronic DHEA administration has a modulatory action on the learning and behavior of the adult male rats.

  6. The neurosteroid dehydroepiandrosterone could improve somatic cell reprogramming.

    Science.gov (United States)

    Shoae-Hassani, Alireza; Sharif, Shiva; Verdi, Javad

    2011-10-01

    Expression of four major reprogramming transgenes, including Oct4, Sox2, Klf4 and c-myc, in somatic cells enables them to have pluripotency. These cells are iPSC (induced pluripotent stem cell) that currently show the greatest potential for differentiation into cells of the three germ lineages. One of the issues facing the successful reprogramming and clinical translation of iPSC technology is the high rate of apoptosis after the reprogramming process. Reprogramming is a stressful process, and the p53 apoptotic pathway plays a negative role in cell growth and self-renewal. Apoptosis via the p53 pathway serves as a major barrier in nuclear somatic cell reprogramming during iPSC generation. DHEA (dehydroepiandrosterone) is an abundant steroid that is produced at high levels in the adrenal cells, and withdrawal of DHEA increases the levels of p53 in the epithelial and stromal cells, resulting in increased levels of apoptotic cells; meanwhile, DHEA decreases cellular apoptosis. DHEA could improve the efficacy of reprogramming yield due to a decrease in apoptosis via the p53 pathway and an increase in cell viability.

  7. Biotransformation of oral dehydroepiandrosterone in elderly men: significant increase in circulating estrogens.

    Science.gov (United States)

    Arlt, W; Haas, J; Callies, F; Reincke, M; Hübler, D; Oettel, M; Ernst, M; Schulte, H M; Allolio, B

    1999-06-01

    The most abundant human steroids, dehydroepiandrosterone (DHEA) and its sulfate ester DHEAS, may have a multitude of beneficial effects, but decline with age. DHEA possibly prevents immunosenescence, and as a neuroactive steroid it may influence processes of cognition and memory. Epidemiological studies revealed an inverse correlation between DHEAS levels and the incidence of cardiovascular disease in men, but not in women. To define a suitable dose for DHEA substitution in elderly men we studied pharmacokinetics and biotransformation of orally administered DHEA in 14 healthy male volunteers (mean age, 58.8 +/- 5.1 yr; mean body mass index, 25.5 +/- 1.5 kg/m2) with serum DHEAS concentrations below 4.1 micromol/L (1500 ng/mL). Diurnal blood sampling was performed on 3 occasions in a single dose, randomized, cross-over design (oral administration of placebo, 50 mg DHEA, or 100 mg DHEA). The intake of 50 mg DHEA led to an increase in serum DHEAS to mean levels of young adult men, whereas 100 mg DHEA induced supraphysiological concentrations [placebo vs. 50 mg DHEA vs. 100 mg DHEA; area under the curve (AUC) 0-12 h (mean +/- SD) for DHEA, 108 +/- 22 vs. 252 +/- 45 vs. 349 +/- 72 nmol/L x h; AUC 0-12 h for DHEAS, 33 +/- 9 vs. 114 +/- 19 vs. 164 +/- 36 micromol/L x h]. Serum testosterone and dihydrotestosterone remained unchanged after DHEA administration. In contrast, 17beta-estradiol and estrone significantly increased in a dose-dependent manner to concentrations still within the upper normal range for men [placebo vs. 50 mg DHEA vs. 100 mg DHEA; AUC 0-12 h for 17beta-estradiol, 510 +/- 198 vs. 635 +/- 156 vs. 700 +/- 209 pmol/L x h (P DHEA seems to be a suitable substitution dose in elderly men, as it leads to serum DHEAS concentrations usually measured in young healthy adults. The DHEA-induced increase in circulating estrogens may contribute to beneficial effects of DHEA in men.

  8. Should dehydroepiandrosterone replacement therapy be provided with glucocorticoids?

    Science.gov (United States)

    Robinzon, B; Cutolo, M

    1999-06-01

    Adrenocorticotrophic hormone (ACTH) induces the concomitant secretion of glucocorticoids (GC) and dehydroepiandrosterone (DHEA) from the adrenal cortex. Whereas GC are catabolic, DHEA is anabolic. Long-term GC administration may result in some deleterious side-effects, such as muscular weakness, atrophy and necrosis, diabetes, fattiness, osteopenia, osteoporosis and avascular necrosis and susceptibility to infections. DHEA ameliorates some deleterious effects of GC, such as diabetes, amino acid deamination, fattiness, hypertension and susceptibility to viraemia. By its anabolic effects in muscles, bones and endothelium, DHEA may diminish the severity of GC-induced myopathy, osteopenia, osteoporosis and avascular necrosis. The natural concomitant secretion of DHEA with GC probably enables the latter to protect the body from ill-effects of stress without exerting their deleterious potency. DHEA secretion diminishes during aging and severe or chronic diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Anti-inflammatory and immunosuppressive effects of GC and androgens, including DHEA, are now well established. On the other hand, administration of GC inhibits ACTH secretion, involutes the adrenal cortex and results in further DHEA deficiency, particularly harmful in chronic autoimmune diseases (i.e. RA, SLE). Therefore, the deleterious side-effects of chronic administration of GC emerges from both their direct catabolic activity and the suppression of DHEA production. Whereas, in males, most androgens come from the testes, in females, under GC supplementation, DHEA deficiency leads to nullification of the androgen-dependent anabolism, leaving them exposed to the GC-catabolic effects to a larger extent. The viewpoint presented here claims that under chronic GC supplementation, DHEA replacement therapy may reduce damage caused by GC administration.

  9. Hair cortisol and dehydroepiandrosterone concentrations in naturally Taenia solium infected pigs in Tanzania

    DEFF Research Database (Denmark)

    Trevisan, Chiara; Montillo, Marta; Prandi, Alberto

    2017-01-01

    The aim of this study was to measure hair cortisol and dehydroepiandrosterone (DHEA) concentrations in naturally Taenia solium infected and non-infected control pigs and assess the effect of an environmental change on the aforementioned parameters. Three hair patches were obtained from 13 T. solium...

  10. Restoring testosterone levels by adding dehydroepiandrosterone to a drospirenone containing combined oral contraceptive : II. Clinical effects

    NARCIS (Netherlands)

    Zimmerman, Y.; Foidart, J. M.; Pintiaux, A.; Minon, J. M.; Fauser, B. C J M; Cobey, K.; Coelingh Bennink, H. J T

    2015-01-01

    Objectives Combined oral contraceptives (COCs) decrease androgen levels, including testosterone (T), which may be associated with sexual dysfunction and mood complaints in some women. We have shown that 'co-administration' of dehydroepiandrosterone (DHEA) to a drospirenone (DRSP)-containing COC

  11. Serum dehydroepiandrosterone levels are associated with lower risk of type 2 diabetes: the Rotterdam Study

    NARCIS (Netherlands)

    A. Brahimaj (Adela); T. Muka (Taulant); M. Kavousi (Maryam); J.S.E. Laven (Joop); A. Dehghan (Abbas); O.H. Franco (Oscar)

    2017-01-01

    textabstractAims/hypothesis: Previous literature documents controversial results for the impact of dehydroepiandrosterone (DHEA) in glucose metabolism. We aimed to assess the associations between serum levels of DHEA and its main derivatives DHEA sulphate (DHEAS) and androstenedione, as well as the

  12. Bovine liverslices: A multifunctional in vitro model to study the prohormone dehydroepiandrosterone (DHEA)

    NARCIS (Netherlands)

    Rijk, J.C.W.; Bovee, T.F.H.; Peijnenburg, A.A.C.M.; Groot, M.J.; Rietjens, I.M.C.M.; Nielen, M.W.F.

    2012-01-01

    Biotransformation of inactive prohormones like dehydroepiandrosterone (DHEA) can lead to the formation of potent androgens and subsequent androgenic responses in target tissues. In the present study, precision-cut bovine liver slices were used to study the effects of DHEA on the metabolite,

  13. Restoring testosterone levels by adding dehydroepiandrosterone to a drospirenone containing combined oral contraceptive : I. Endocrine effects

    NARCIS (Netherlands)

    Zimmerman, Y.; Foidart, J. M.; Pintiaux, A.; Minon, J. M.; Fauser, B. C J M; Cobey, K.; Coelingh Bennink, H. J T

    2015-01-01

    Objectives Combined oral contraceptives (COCs) decrease testosterone (T) levels. This study investigated restoration of T and other androgen concentrations during COC use by 'co-administration' of dehydroepiandrosterone (DHEA). Study design In this randomized, double-blind, placebo-controlled study

  14. Feasibility of a liver transcriptomics approach to assess bovine treatment with the prohormone dehydroepiandrosterone (DHEA)

    NARCIS (Netherlands)

    Rijk, J.C.W.; Peijnenburg, A.A.C.M.; Hendriksen, P.J.M.; Hende, van J.; Groot, M.J.; Nielen, M.W.F.

    2010-01-01

    Background Within the European Union the use of growth promoting agents in animal production is prohibited. Illegal use of natural prohormones like dehydroepiandrosterone (DHEA) is hard to prove since prohormones are strongly metabolized in vivo. In the present study, we investigated the feasibility

  15. Fatigue in patients with systemic lupus erythematosus : the role of dehydroepiandrosterone sulphate

    NARCIS (Netherlands)

    Overman, C. L.; Hartkamp, A.; Bossema, E. R.; Bijl, M.; Godaert, G. L. R.; Bijlsma, J. W. J.; Derksen, R. H. W. M.; Geenen, R.

    2012-01-01

    Fatigue is a major problem in systemic lupus erythematosus (SLE), but the physiological substrate of this fatigue is largely unclear. To examine if low levels of dehydroepiandrosterone (DHEA) and its sulphate DHEAS play a role in SLE fatigue, we compared: 1) DHEAS levels and fatigue between 60 femal

  16. Dynamics of Adrenal Steroids Are Related to Variations in Th1 and Treg Populations during Mycobacterium tuberculosis Infection in HIV Positive Persons

    Science.gov (United States)

    Quiroga, Maria Florencia; Angerami, Matias Tomas; Santucci, Natalia; Ameri, Diego; Francos, Jose Luis; Wallach, Jorge; Sued, Omar; Cahn, Pedro; Salomón, Horacio; Bottasso, Oscar

    2012-01-01

    Tuberculosis (TB) remains the most frequent cause of illness and death from an infectious agent, and its interaction with HIV has devastating effects. We determined plasma levels of dehydroepiandrosterone (DHEA), its circulating form DHEA-suphate (DHEA-s) and cortisol in different stages of M. tuberculosis infection, and explored their role on the Th1 and Treg populations during different scenarios of HIV-TB coinfection, including the immune reconstitution inflammatory syndrome (IRIS), a condition related to antiretroviral treatment. DHEA levels were diminished in HIV-TB and HIV-TB IRIS patients compared to healthy donors (HD), HIV+ individuals and HIV+ individuals with latent TB (HIV-LTB), whereas dehydroepiandrosterone sulfate (DHEA-s) levels were markedly diminished in HIV-TB IRIS individuals. HIV-TB and IRIS patients presented a cortisol/DHEA ratio significantly higher than HIV+, HIV-LTB and HD individuals. A positive correlation was observed between DHEA-s and CD4 count among HIV-TB individuals. Conversely, cortisol plasma level inversely correlated with CD4 count within HIV-TB individuals. M. tuberculosis-specific Th1 lymphocyte count was increased after culturing PBMC from HIV-TB individuals in presence of DHEA. We observed an inverse correlation between DHEA-s plasma level and Treg frequency in co-infected individuals, and CD4+FoxP3+ Treg frequency was increased in HIV-TB and IRIS patients compared to other groups. Strikingly, we observed a prominent CD4+CD25-FoxP3+ population across HIV-TB and HIV-TB IRIS patients, which frequency correlated with DHEA plasma level. Finally, DHEA treatment negatively regulated FoxP3 expression without altering Treg frequency in co-infected patients. These data suggest an enhancing role for DHEA in the immune response against M. tuberculosis during HIV-TB coinfection and IRIS. PMID:22431997

  17. Dynamics of adrenal steroids are related to variations in Th1 and Treg populations during Mycobacterium tuberculosis infection in HIV positive persons.

    Directory of Open Access Journals (Sweden)

    Maria Florencia Quiroga

    Full Text Available Tuberculosis (TB remains the most frequent cause of illness and death from an infectious agent, and its interaction with HIV has devastating effects. We determined plasma levels of dehydroepiandrosterone (DHEA, its circulating form DHEA-suphate (DHEA-s and cortisol in different stages of M. tuberculosis infection, and explored their role on the Th1 and Treg populations during different scenarios of HIV-TB coinfection, including the immune reconstitution inflammatory syndrome (IRIS, a condition related to antiretroviral treatment. DHEA levels were diminished in HIV-TB and HIV-TB IRIS patients compared to healthy donors (HD, HIV+ individuals and HIV+ individuals with latent TB (HIV-LTB, whereas dehydroepiandrosterone sulfate (DHEA-s levels were markedly diminished in HIV-TB IRIS individuals. HIV-TB and IRIS patients presented a cortisol/DHEA ratio significantly higher than HIV+, HIV-LTB and HD individuals. A positive correlation was observed between DHEA-s and CD4 count among HIV-TB individuals. Conversely, cortisol plasma level inversely correlated with CD4 count within HIV-TB individuals. M. tuberculosis-specific Th1 lymphocyte count was increased after culturing PBMC from HIV-TB individuals in presence of DHEA. We observed an inverse correlation between DHEA-s plasma level and Treg frequency in co-infected individuals, and CD4+FoxP3+ Treg frequency was increased in HIV-TB and IRIS patients compared to other groups. Strikingly, we observed a prominent CD4+CD25-FoxP3+ population across HIV-TB and HIV-TB IRIS patients, which frequency correlated with DHEA plasma level. Finally, DHEA treatment negatively regulated FoxP3 expression without altering Treg frequency in co-infected patients. These data suggest an enhancing role for DHEA in the immune response against M. tuberculosis during HIV-TB coinfection and IRIS.

  18. Ferrous Sulfate (Iron)

    Science.gov (United States)

    Ferrous sulfate provides the iron needed by the body to produce red blood cells. It is used ... Ferrous sulfate comes as regular, coated, and extended-release (long-acting) tablets; regular and extended-release capsules; ...

  19. Stimulation of androgen-dependent gene expression by the adrenal precursors dehydroepiandrosterone and androstenedione in the rat ventral prostate

    Energy Technology Data Exchange (ETDEWEB)

    Labrie, C.; Simard, J.; Zhao, H.F.; Belanger, A.; Pelletier, G.; Labrie, F. (Laval Univ. Medical Center, Quebec (Canada))

    1989-06-01

    Androgens play a major role in the development, growth, and function of accessory sexual organs, especially the prostate. However, the testis is not the sole source of circulating androgens in man, since the adrenal gland secretes dehydroepiandrosterone (DHEA), DHEA sulfate, and androstenedione (delta 4-dione) in large quantities. The aim of the present study was to investigate the effect of plasma concentrations of DHEA and delta 4-dione similar to those found in adult man on sensitive and specific markers of androgen action in the rat ventral prostate. In addition to ventral prostate weight, we have measured the steady state levels of the mRNAs encoding the C1 component of rat prostatic binding protein (PBP-C1) and spermine-binding protein (SBP) using 35S-labeled cDNA probes for in situ hybridization. One week after castration, ventral prostate weight fell 84%, while prostatic 5 alpha-dihydrotestosterone (DHT) and androgen-dependent mRNAs were undetectable. When administered via Silastic implants to castrated adult rats for 1 week, plasma concentrations of 1.37 +/- 0.06 ng/ml DHEA or 0.43 +/- 0.08 ng/ml delta 4-dione independently caused increases in ventral prostate weight to 33% and 65% of normal values, respectively. The same plasma levels of DHEA and delta 4-dione resulted in high intraprostatic levels of DHT to 1.19 +/- 0.34 and 3.66 +/- 0.89 ng/g tissue, respectively. Furthermore, DHEA caused an increase in the steady state levels of PBP-C1 and SBP mRNAs to 50% and 57% of the normal state, respectively, while delta 4-dione caused increases corresponding to 80% and 119% of control values, respectively. Castrated adult rats receiving testosterone at a concentration of 1.66 +/- 0.37 ng/ml plasma maintained normal ventral prostate weight and gene expression levels.

  20. Effects of dehydroepiandrosterone replacement in elderly men on event-related potentials, memory, and well-being.

    Science.gov (United States)

    Wolf, O T; Naumann, E; Hellhammer, D H; Kirschbaum, C

    1998-09-01

    In humans, concentrations of the adrenal steroid hormone dehydroepiandrosterone (DHEA) and its sulfate ester (DHEAS) decline with age. Results from studies in rodents have suggested that DHEA administration can improve memory performance as well as neuronal plasticity. However, a first study from our laboratory could not demonstrate beneficial effects of DHEA substitution on cognitive performance and well-being in elderly subjects. To further evaluate whether DHEA replacement has effects on the central nervous system, an experiment using event-related potentials (ERPs) was conducted. In this placebo-controlled crossover study, 17 elderly men (mean age, 71.1 +/- 1.7 yr; range 59-81 yr) took placebo or DHEA (50 mg/day) for 2 weeks (double blind). After each treatment period subjects participated in an auditory oddball paradigm with three oddball blocks. In the first two blocks subjects had to count the rare tone silently, whereas, in the third block they had to press a button. In addition, memory tests assessing visual, spatial, and semantic memory as well as questionnaires on psychological and physical well-being were presented. Baseline DHEAS levels were lower compared with young adults. After 2-week DHEA replacement, DHEAS levels rose 5-fold to levels observed in young men. DHEA substitution modulated the P3 component of the ERPs, which reflects information updating in short-term memory. P3 amplitude was increased after DHEA administration, and only selectively in the second oddball block. DHEA did not influence P3 latency. Moreover, DHEA did not enhance memory or mood. A 2-week DHEA replacement in elderly men results in changes in electrophysiological indices of central nervous system stimulus processing if the task is performed repeatedly. However, these effects do not appear to be strong enough to improve memory or mood.

  1. Dehydroepiandrosterone and the relationship with aging and memory: a possible link with protein kinase C functional machinery.

    Science.gov (United States)

    Racchi, M; Govoni, S; Solerte, S B; Galli, C L; Corsini, E

    2001-11-01

    A progressive decline of cognitive and memory functions, compared to the average young-life performance, characterizes brain aging. The changes in performance may depend upon altered activity of neurotransmitters acting on attention and memory trace formation (acetylcholine, catecholamines, glutamate, for example) or the failure of the transduction mechanisms linked to receptor activation. One of the fundamental cellular changes associated with brain aging is the alteration of mechanisms involving the activity of the calcium-phospholipid-dependent protein kinase C (PKC). A crucial event for the activation of protein kinase C is its translocation from the cytosol to different intracellular sites and recent studies have demonstrated the key role played by several anchoring proteins in this mechanism. The defective activation of PKC-dependent pathways during aging is due to a defective mechanism of translocation of the kinase because of reduced levels of the major anchoring protein RACK-1 (receptor for activated C kinase). Pharmacological strategies aimed at the correction of age-associated memory deficits have been mostly focused on neurotransmitters using direct or indirect agonists. More recently, attention has been paid to the memory enhancing properties of some steroid hormones, namely 'neurosteroids'. Among these the activities of dehydroepiandrosterone (DHEA), pregnenolone (PREG) and their sulfates, have been extensively studied. These neuroactive steroids, can regulate neuronal function through their concurrent influence on transmitter-gated ion channels and gene expression. We addressed the possibility that DHEA, among other neurosteroids, could modulate directly the age-associated impairment of PKC signal transduction and provide experimental evidence that DHEA can revert the alteration of RACK-1 anchoring protein expression.

  2. Measurements of Serum DHEA and DHEA Sulphate Levels Improve the Accuracy of the Low-Dose Cosyntropin Test in the Diagnosis of Central Adrenal Insufficiency

    Science.gov (United States)

    Sayyed Kassem, Laure; El Sibai, Katia; Chaiban, Joumana; Abdelmannan, Dima

    2012-01-01

    Background and Objectives: The diagnosis of central adrenal insufficiency (AI) continues to be challenging, especially when it is partial. We have recently demonstrated the value of measuring serum dehydroepiandrosterone sulfate (DHEA-S) in establishing the diagnosis of central AI. The current investigation examined the added value of measuring serum dehydroepiandrosterone (DHEA) levels during low-dose (1 μg) cosyntropin (LDC) stimulation in patients suspected to have central AI. Methods: Baseline and LDC-stimulated cortisol, DHEA, and DHEA-S were measured preoperatively in 155 consecutive patients with pituitary masses and 63 healthy subjects. Hypothalamic-pituitary adrenal (HPA) function was normal (NL-HPA) in 97 of the patients and was impaired (impaired HPA) in 58 patients. Patients with NL-HPA underwent surgical removal of the sellar masses and received no glucocorticoids before, during, or after surgery. Results: Baseline and LDC-stimulated serum cortisol, DHEA, and DHEA-S in patients with NL-HPA were similar to those of normal subjects. In contrast, patients with impaired HPA had lower baseline and LDC-stimulated serum cortisol, DHEA, and DHEA-S levels. There were 18 subjects in the latter group whose LDC-stimulated serum cortisol levels were greater than 18.0 μg/dl. In those 18 subjects, baseline and LDC-stimulated DHEA and DHEA-S levels were similar to the whole group of patients with impaired HPA function. The molar ratio of cortisol to DHEA did not change with LDC stimulation in normal subjects and those with NL-HPA. In contrast, patients with impaired HPA had a higher baseline cortisol to DHEA molar ratio that increased further with LDC stimulation. Conclusions: Patients with impaired HPA function have a more severe loss in DHEA secretion than that of glucocorticoids. Measurements of serum DHEA levels during LDC simulation provide additional valuable information that improves the diagnostic accuracy of LDC in patients suspected to have central AI. We

  3. Effects of 7-keto Dehydroepiandrosterone on Voluntary Ethanol Intake in Male Rats

    OpenAIRE

    Worrel, Mary E.; Gurkovskaya, Olga V.; Leonard, Stuart T.; Lewis, Peter B.; Winsauer, Peter J.

    2010-01-01

    Administration of dehydroepiandrosterone (DHEA), a neurosteroid that can negatively modulate the GABAA receptor, has been shown to decrease voluntary intake of ethanol in rats. In vivo, DHEA can be metabolized to a variety of metabolites, including 7-keto DHEA, a metabolite without the prohormonal effects of DHEA. This study compared the effectiveness of 7-keto DHEA to DHEA for reducing ethanol intake in the same group of rats. The subjects, previously trained to drink ethanol using a sacchar...

  4. Dehydroepiandrosterone (DHEA) Feeding Protects Liver Steatosis in Obese Breast Cancer Rat Model

    OpenAIRE

    Reza Hakkak; Andrea Bell; Soheila Korourian

    2017-01-01

    Obesity is a major health problem in the US and globally. Obesity is associated with the risk of cardiovascular disease, type 2 diabetes, cancers, hyperlipidemia, and liver steatosis development. Dehydroepiandrosterone (DHEA) is a dietary supplement used as an anti-obesity supplement. Previously, we reported that DHEA feeding protects 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary tumors. The objectives of this study were to investigate the effects of obesity and DHEA feeding on liver ...

  5. Administration of Dehydroepiandrosterone (DHEA) Enhances Visual-Spatial Performance in Post-Menopausal Women

    OpenAIRE

    Stangl, Bethany; Hirshman, Elliot; Verbalis, Joseph

    2011-01-01

    The current paper examines the effect of administering Dehydroepiandrosterone (DHEA) on visual-spatial performance in post-menopausal women (N=24, ages 55-80). The concurrent reduction of serum DHEA levels and visual-spatial performance in this population, coupled with the documented effects of DHEA’s androgenic metabolites on visual-spatial performance, suggest that DHEA administration may enhance visual-spatial performance. The current experiment used a double-blind placebo-controlled cross...

  6. Evaluation of serum cortisol and dehydroepiandrosterone sulphate levels in parkinson patients with and without postural instability

    OpenAIRE

    Murat Gültekin; Recep Baydemir; Sevda İsmailoğulları; Fatih Tanrıverdi; Meral Mirza

    2014-01-01

    Objective: Parkinson\\'s disease (PD) is the second most common neurodegenerative disease. During PD many disorders occur in the neuroendocrine mechanism along with autonomic dysfunction. The aim of this study was to evaluate the values of cortisol and dehydroepiandrosterone sulphate (DHEAS) in idiopathic PD patients with postural instability (PI) in the medium and advanced stages of the disease. Methods: Three groups were included in this study; patients with PI, patients without PI and c...

  7. Pseudomonas aeruginosa arylsulfatase: a purified enzyme for the mild hydrolysis of steroid sulfates.

    Science.gov (United States)

    Stevenson, Bradley J; Waller, Christopher C; Ma, Paul; Li, Kunkun; Cawley, Adam T; Ollis, David L; McLeod, Malcolm D

    2015-10-01

    The hydrolysis of sulfate ester conjugates is frequently required prior to analysis for a range of analytical techniques including gas chromatography-mass spectrometry (GC-MS). Sulfate hydrolysis may be achieved with commercial crude arylsulfatase enzyme preparations such as that derived from Helix pomatia but these contain additional enzyme activities such as glucuronidase, oxidase, and reductase that make them unsuitable for many analytical applications. Strong acid can also be used to hydrolyze sulfate esters but this can lead to analyte degradation or increased matrix interference. In this work, the heterologously expressed and purified arylsulfatase from Pseudomonas aeruginosa is shown to promote the mild enzyme-catalyzed hydrolysis of a range of steroid sulfates. The substrate scope of this P. aeruginosa arylsulfatase hydrolysis is compared with commercial crude enzyme preparations such as that derived from H. pomatia. A detailed kinetic comparison is reported for selected examples. Hydrolysis in a urine matrix is demonstrated for dehydroepiandrosterone 3-sulfate and epiandrosterone 3-sulfate. The purified P. aeruginosa arylsulfatase contains only sulfatase activity allowing for the selective hydrolysis of sulfate esters in the presence of glucuronide conjugates as demonstrated in the short three-step chemoenzymatic synthesis of 5α-androstane-3β,17β-diol 17-glucuronide (ADG, 1) from epiandrosterone 3-sulfate. The P. aeruginosa arylsulfatase is readily expressed and purified (0.9 g per L of culture) and thus provides a new and selective method for the hydrolysis of steroid sulfate esters in analytical sample preparation. Copyright © 2015 John Wiley & Sons, Ltd.

  8. Dehydroepiandrosterone intra vaginal administration for the management of postmenopausal vulvovaginal atrophy.

    Science.gov (United States)

    Archer, David F

    2015-01-01

    The effects of intravaginal administration of dehydroepiandrosterone (DHEA) for the management of symptomatic vulvovaginal atrophy are reviewed. A literature search related to vulvovaginal atrophy, vaginal atrophy, atrophic vaginitis, estrogen, dehydroepiandrosterone, vulvar itching, burning, dryness, dyspareunia, and libido was performed. Relevant articles addressing the incidence, management, and outcome of DHEA therapy were identified and used for this Expert Opinion. DHEA compared to a placebo is an effective treatment improving symptoms of vaginal atrophy: dyspareunia, burning, itching, and dryness. Objective parameters of vaginal atrophy, specifically pH, vaginal maturation index (VMI), and investigator-evaluated changes in the vagina: moisture, epithelia integrity and color were improved compared to baseline and placebo. There were significant improvements in libido and dyspareunia with the intravaginal use of DHEA that contribute to improved quality of life for postmenopausal women. Dehydroepiandrosterone administered intravaginally on a daily basis is an effective treatment for symptoms, and signs of vulvovaginal atrophy along with libido in postmenopausal women. This article is part of a Special Issue entitled 'Essential role of DHEA'.

  9. Tyrosine Sulfation of Statherin

    Directory of Open Access Journals (Sweden)

    C. Kasinathan, N. Gandhi, P. Ramaprasad, P. Sundaram, N. Ramasubbu

    2007-01-01

    Full Text Available Tyrosylprotein sulfotransferase (TPST, responsible for the sulfation of a variety of secretory and membrane proteins, has been identified and characterized in submandibular salivary glands (William et al. Arch Biochem Biophys 1997; 338: 90-96. In the present study we demonstrate the sulfation of a salivary secretory protein, statherin, by the tyrosylprotein sulfotransferase present in human saliva. Optimum statherin sulfation was observed at pH 6.5 and at 20 mm MnCl2. Increase in the level of total sulfation was observed with increasing statherin concentration. The Km value of tyrosylprotein sulfotransferase for statherin was 40 μM. Analysis of the sulfated statherin product on SDS-polyacrylamide gel electrophoresis followed by autoradiography revealed 35S-labelling of a 5 kDa statherin. Further analysis of the sulfated statherin revealed the sulfation on tyrosyl residue. This study is the first report demonstrating tyrosine sulfation of a salivary secretory protein. The implications of this sulfation of statherin in hydroxyapatite binding and Actinomyces viscosus interactions are discussed.

  10. Roles of heparan sulfate sulfation in dentinogenesis.

    Science.gov (United States)

    Hayano, Satoru; Kurosaka, Hiroshi; Yanagita, Takeshi; Kalus, Ina; Milz, Fabian; Ishihara, Yoshihito; Islam, Md Nurul; Kawanabe, Noriaki; Saito, Masahiro; Kamioka, Hiroshi; Adachi, Taiji; Dierks, Thomas; Yamashiro, Takashi

    2012-04-06

    Cell surface heparan sulfate (HS) is an essential regulator of cell signaling and development. HS traps signaling molecules, like Wnt in the glycosaminoglycan side chains of HS proteoglycans (HSPGs), and regulates their functions. Endosulfatases Sulf1 and Sulf2 are secreted at the cell surface to selectively remove 6-O-sulfate groups from HSPGs, thereby modifying the affinity of cell surface HSPGs for its ligands. This study provides molecular evidence for the functional roles of HSPG sulfation and desulfation in dentinogenesis. We show that odontogenic cells are highly sulfated on the cell surface and become desulfated during their differentiation to odontoblasts, which produce tooth dentin. Sulf1/Sulf2 double null mutant mice exhibit a thin dentin matrix and short roots combined with reduced expression of dentin sialophosphoprotein (Dspp) mRNA, encoding a dentin-specific extracellular matrix precursor protein, whereas single Sulf mutants do not show such defective phenotypes. In odontoblast cell lines, Dspp mRNA expression is potentiated by the activation of the Wnt canonical signaling pathway. In addition, pharmacological interference with HS sulfation promotes Dspp mRNA expression through activation of Wnt signaling. On the contrary, the silencing of Sulf suppresses the Wnt signaling pathway and subsequently Dspp mRNA expression. We also show that Wnt10a protein binds to cell surface HSPGs in odontoblasts, and interference with HS sulfation decreases the binding affinity of Wnt10a for HSPGs, which facilitates the binding of Wnt10a to its receptor and potentiates the Wnt signaling pathway, thereby up-regulating Dspp mRNA expression. These results demonstrate that Sulf-mediated desulfation of cellular HSPGs is an important modification that is critical for the activation of the Wnt signaling in odontoblasts and for production of the dentin matrix.

  11. Polymorphisms of STS gene and SULT2A1 gene and neurosteroid levels in Han Chinese boys with attention-deficit/hyperactivity disorder: an exploratory investigation

    Science.gov (United States)

    Wang, Liang-Jen; Chan, Wen-Ching; Chou, Miao-Chun; Chou, Wen-Jiun; Lee, Min-Jing; Lee, Sheng-Yu; Lin, Pao-Yen; Yang, Yi-Hsin; Yen, Cheng-Fang

    2017-01-01

    This study examined the relationships among polymorphisms of the STS gene and SULT2A1 gene, dehydroepiandrosterone (DHEA) and its sulfated form (DHEA-S), and characteristics of attention-deficit/hyperactivity disorder (ADHD). We used cheek swabs to obtain the genomic DNA of 200 ADHD male probands (mean age: 8.7 years), 192 patients’ mothers and 157 patients’ fathers. Three SNPs in the STS gene (rs6639786, rs2270112, and rs17268988) and one SNP in the SULT2A1 gene (rs182420) were genotyped. Saliva samples were collected from the ADHD patients to analyze DHEA and DHEA-S levels. The behavioral symptoms were evaluated with the Swanson, Nolan, and Pelham, and Version IV Scale for ADHD (SNAP-IV), and the neuropsychological function was assessed using the Conners’ Continuous Performance Tests (CPT). We found the C allele of rs2270112 within the STS gene to be over-transmitted in males with ADHD. Polymorphisms of rs182420 within the SULT2A1 gene were not associated with ADHD. In addition, the C allele carriers of rs2270112 demonstrated significantly higher DHEA-S levels than the G allele carriers. Levels of DHEA were positively correlated with attention as measured by the CPT. These findings support a potential role in the underlying biological pathogenesis of ADHD with regard to STS polymorphisms and neurosteroid levels. PMID:28367959

  12. Coordination of cortisol response to social evaluative threat with autonomic and inflammatory responses is moderated by stress appraisals and affect.

    Science.gov (United States)

    Laurent, Heidemarie K; Lucas, Todd; Pierce, Jennifer; Goetz, Stefan; Granger, Douglas A

    2016-07-01

    Recent approaches to stress regulation have emphasized coordination among multiple biological systems. This study builds on evidence that hypothalamic-pituitary-adrenal (HPA) axis activity should be considered in coordination with other stress-sensitive biological systems to characterize healthy responses. Healthy African-Americans (n=115) completed the Trier Social Stress Test, and biological responses were assessed through salivary cortisol, dehydroepiandrosterone-sulfate (DHEA-S), alpha amylase (sAA), and C-reactive protein (sCRP). Multilevel modeling demonstrated that cortisol responses typically aligned with changes in DHEA-S, sAA, and sCRP across the session. At the same time, the degree of cortisol coordination with sAA and sCRP varied by participants' subjective stress following the task; participants with higher secondary stress appraisals showed greater cortisol-sAA alignment, whereas those experiencing more negative affect showed greater cortisol-sCRP alignment. Results highlight the importance of a multisystem approach to stress and suggest that positive HPA axis coordination with the autonomic response, but not with the immune/inflammatory response, may be adaptive.

  13. Tactics for modeling multiple salivary analyte data in relation to behavior problems: Additive, ratio, and interaction effects.

    Science.gov (United States)

    Chen, Frances R; Raine, Adrian; Granger, Douglas A

    2015-01-01

    Individual differences in the psychobiology of the stress response have been linked to behavior problems in youth yet most research has focused on single signaling molecules released by either the hypothalamic-pituitary-adrenal axis or the autonomic nervous system. As our understanding about biobehavioral relationships develops it is clear that multiple signals from the biological stress systems work in coordination to affect behavior problems. Questions are raised as to whether coordinated effects should be statistically represented as ratio or interactive terms. We address this knowledge gap by providing a theoretical overview of the concepts and rationales, and illustrating the analytical tactics. Salivary samples collected from 446 youth aged 11-12 were assayed for salivary alpha-amylase (sAA), dehydroepiandrosterone-sulfate (DHEA-s) and cortisol. Coordinated effect of DHEA-s and cortisol, and coordinated effect of sAA and cortisol on externalizing and internalizing problems (Child Behavior Checklist) were tested with the ratio and the interaction approaches using multi-group path analysis. Findings consistent with previous studies include a positive association between cortisol/DHEA-s ratio and internalizing problems; and a negative association between cortisol and externalizing problems conditional on low levels of sAA. This study highlights the importance of matching analytical strategy with research hypothesis when integrating salivary bioscience into research in behavior problems. Recommendations are made for investigating multiple salivary analytes in relation to behavior problems. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. The ceric sulfate dosimeter

    DEFF Research Database (Denmark)

    Bjergbakke, Erling

    1970-01-01

    The process employed for the determination of absorbed dose is the reduction of ceric ions to cerous ions in a solution of ceric sulfate and cerous sulfate in 0.8N sulfuric acid: Ce4+→Ce 3+ The absorbed dose is derived from the difference in ceric ion concentration before and after irradiation...

  15. Heparan sulfate biosynthesis

    DEFF Research Database (Denmark)

    Multhaupt, Hinke A B; Couchman, John R

    2012-01-01

    Heparan sulfate is perhaps the most complex polysaccharide known from animals. The basic repeating disaccharide is extensively modified by sulfation and uronic acid epimerization. Despite this, the fine structure of heparan sulfate is remarkably consistent with a particular cell type. This suggests...... that the synthesis of heparan sulfate is tightly controlled. Although genomics has identified the enzymes involved in glycosaminoglycan synthesis in a number of vertebrates and invertebrates, the regulation of the process is not understood. Moreover, the localization of the various enzymes in the Golgi apparatus has......-quality resolution of the distribution of enzymes. The EXT2 protein, which when combined as heterodimers with EXT1 comprises the major polymerase in heparan sulfate synthesis, has been studied in depth. All the data are consistent with a cis-Golgi distribution and provide a starting point to establish whether all...

  16. Liver X receptor alpha mediated genistein induction of human dehydroepiandrosterone sulfotransferase (hSULT2A1) in Hep G2 cells.

    Science.gov (United States)

    Chen, Yue; Zhang, Shunfen; Zhou, Tianyan; Huang, Chaoqun; McLaughlin, Alicia; Chen, Guangping

    2013-04-15

    Cytosolic sulfotransferases are one of the major families of phase II drug metabolizing enzymes. Sulfotransferase-catalyzed sulfonation regulates hormone activities, metabolizes drugs, detoxifies xenobiotics, and bioactivates carcinogens. Human dehydroepiandrosterone sulfotransferase (hSULT2A1) plays important biological roles by sulfating endogenous hydroxysteroids and exogenous xenobiotics. Genistein, mainly existing in soy food products, is a naturally occurring phytoestrogen with both chemopreventive and chemotherapeutic potential. Our previous studies have shown that genistein significantly induces hSULT2A1 in Hep G2 and Caco-2 cells. In this study, we investigated the roles of liver X receptor (LXRα) in the genistein induction of hSULT2A1. LXRs have been shown to induce expression of mouse Sult2a9 and hSULT2A1 gene. Our results demonstrate that LXRα mediates the genistein induction of hSULT2A1, supported by Western blot analysis results, hSULT2A1 promoter driven luciferase reporter gene assay results, and mRNA interference results. Chromatin immunoprecipitation (ChIP) assay results demonstrate that genistein increase the recruitment of hLXRα binding to the hSULT2A1 promoter. These results suggest that hLXRα plays an important role in the hSULT2A1 gene regulation. The biological functions of phytoestrogens may partially relate to their induction activity toward hydroxysteroid SULT.

  17. Exogenous dopamine induces dehydroepiandrosterone sulfotransferase (rSULT2A1) in rat liver and changes the pharmacokinetic profile of moxifloxacin in rats.

    Science.gov (United States)

    Shao, Xueyan; Li, Jian; Wang, Siyuan; Chen, Guangping; Xu, Jiaojiao; Ji, Xiwei; Li, Liang; Lu, Wei; Zhou, Tianyan

    2015-02-01

    Dehydroepiandrosterone sulfotransferase (SULT2A1) plays an important role in the detoxification of hydroxyl-containing xenobitotics and in the regulation of the biological activities of hydroxysteroids. Although dopamine (DA) is a vital neurotransmitter, DA also has some special functions in outer peripheral system and takes effect by binding with dopamine receptors including five subtypes (D1-D5). The objective of this study was to investigate the effect of exogenous DA on both the regulation of rSULT2A1 (rat SULT2A1) and the pharmacokinetics of moxifloxacin which is a specific substrate of rSULT2A1. After different doses of DA (0, 2, 10 and 100 mg/kg/d) were administrated to both male and female rats for 7 days, the activity, protein level and mRNA expression of rSULT2A1 increased significantly. Moreover, both Cmax and AUC of moxifloxacin decreased and AUC of moxifloxacin sulfate conjugate metabolite increased significantly when moxifloxacin was administered to rats with DA pretreatment. Additionally, D1 expression in liver and cAMP concentration also increased after the treatment with DA. Overall these results suggest that exogenous DA may induce rSULT2A1 in rat liver and may further change the pharmacokinetic characteristics of some substrates of SULT2A1, and the activation of D1-like receptor is probably involved in rSULT2A1 induction by DA.

  18. Clinical review: The benefits and harms of systemic dehydroepiandrosterone (DHEA) in postmenopausal women with normal adrenal function: a systematic review and meta-analysis.

    Science.gov (United States)

    Elraiyah, Tarig; Sonbol, Mohamad Bassam; Wang, Zhen; Khairalseed, Tagwa; Asi, Noor; Undavalli, Chaitanya; Nabhan, Mohammad; Altayar, Osama; Prokop, Larry; Montori, Victor M; Murad, Mohammad Hassan

    2014-10-01

    Exogenous dehydroepiandrosterone (DHEA) therapy has been proposed to replenish the depletion of endogenous DHEA and its sulfate form, which occurs with advancing age and is thought to be associated with loss of libido and menopausal symptoms. We conducted a systematic review and meta-analysis to summarize the evidence supporting the use of systemic DHEA in postmenopausal women with normal adrenal function. We searched MEDLINE, EMBASE, PsycInfo, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus through January 2014. Pairs of reviewers, working independently, selected studies and extracted data from eligible randomized controlled trials (RCTs). We used the random-effects model to pool across studies and evaluated heterogeneity using the I(2) statistic. We included 23 RCTs with moderate to high risk of bias enrolling 1188 women. DHEA use was not associated with significant improvement in libido or sexual function (standardized mean difference, 0.35; 95% confidence interval, -0.02 to 0.73; P value = .06; I(2) = 62%). There was also no significant effect of DHEA on serious adverse effects, serum lipids, serum glucose, weight, body mass index, or bone mineral density. This evidence warranted low confidence in the results, mostly due to imprecision, risk of bias, and inconsistency across RCTs. Evidence warranting low confidence suggests that DHEA administration does not significantly impact sexual symptoms or selected metabolic markers in postmenopausal women with normal adrenal function.

  19. Differential effect of dehydroepiandrosterone and its steroid precursor pregnenolone against the behavioural deficits in CO-exposed mice.

    Science.gov (United States)

    Maurice, T; Phan, V; Sandillon, F; Urani, A

    2000-02-25

    The neuroactive steroids pregnenolone (3beta-hydroxy-5-pregnen-20-one) and dehydroepiandrosterone (DHEA, 3alpha-hydroxy-5-androstene-17-one) are negative allosteric modulators of the GABA(A) receptors and positive modulators of acetylcholine, NMDA and sigma(1) receptors. Pregnenolone was recently shown to potentiate the neuronal damage induced by excessive glutamate in cell culture models, whereas dehydroepiandrosterone was reported to present some neuroprotective activity. The in vivo relevance of these effects was investigated in mice submitted to an hypoxic insult, the repeated exposure to carbon monoxide (CO) gas, a model that leads to neurodegeneration in the CA(1) hippocampal area and learning deficits. Recording spontaneous alternation behaviour in the Y-maze assessed short-term memory and long-term memory was examined using a passive avoidance task. After exposure to CO, mice showed a progressive deterioration of their learning ability, reaching significance after 3 days and being maximal after 7 days. Pregnenolone administered before CO significantly facilitated the hypoxia-related deficits, which could be measured 1 day after CO and appeared maximal after 3 days. Dizocilpine blocked the deficits in vehicle- and pregnenolone-treated CO-exposed animals, showing that pregnenolone selectively facilitated the NMDA receptor-dependent excitotoxicity. Dehydroepiandrosterone blocked the appearance of the CO-induced deficits, even after 7 days. Interestingly, the sigma(1) receptor antagonist N, N-dipropyl-2-(4-methoxy-3-(2-phenylethoxy)phenyl)ethylamine (NE-100) failed to affect the dehydroepiandrosterone-induced protection, showing the lack of involvement of sigma(1) receptors. Cresyl violet-stained sections of the mouse hippocampal formation showed that the neurodegeneration observed in the CA(1) area after exposure to CO was augmented by pregnenolone and blocked by dehydroepiandrosterone. These results show that pregnenolone and dehydroepiandrosterone, although

  20. Hair cortisol and dehydroepiandrosterone concentrations in naturally Taenia solium infected pigs in Tanzania

    DEFF Research Database (Denmark)

    Trevisan, Chiara; Montillo, Marta; Prandi, Alberto

    2017-01-01

    The aim of this study was to measure hair cortisol and dehydroepiandrosterone (DHEA) concentrations in naturally Taenia solium infected and non-infected control pigs and assess the effect of an environmental change on the aforementioned parameters. Three hair patches were obtained from 13 T. solium...... infected and 15 non-infected controls sows, respectively corresponding to 3 time points (prior to, at and approximately two weeks after arrival at the research facility). Cortisol and DHEA were extracted using methanol and analysed by radio immune assay. Mean hair cortisol concentrations were significantly...... lower (pDHEA...

  1. Direct Sulfation of Limestone

    DEFF Research Database (Denmark)

    Hu, Guilin; Dam-Johansen, Kim; Wedel, Stig

    2007-01-01

    The direct sulfation of limestone was studied in a laboratory fixed-bed reactor. It is found that the direct sulfation of limestone involves nucleation and crystal grain growth of the solid product (anhydrite). At 823 K and at low-conversions (less than about 0.5 %), the influences of SO2, O-2...... and CO2 on the direct sulfation of limestone corresponds to apparent reaction orders of about 0.2, 0.2 and -0.5, respectively. Water is observed to promote the sulfation reaction and increase the apparent reaction orders of SO2 and O-2. The influence of O-2 at high O-2 concentrations (> about 15...... %) becomes negligible. In the temperature interval from 723 K to 973 K, an apparent activation energy of about 104 kJ/mol is observed for the direct sulfation of limestone. At low temperatures and low conversions, the sulfation process is most likely under mixed control by chemical reaction and solid...

  2. Association of DHEA, DHEAS, and cortisol with childhood trauma exposure and post-traumatic stress disorder.

    Science.gov (United States)

    Van Voorhees, Elizabeth E; Dennis, Michelle F; Calhoun, Patrick S; Beckham, Jean C

    2014-01-01

    There has been a great deal of interest in the role of the neuroendocrine hormones of the hypothalamic-pituitary-adrenal (HPA) axis in the expression of stress-related psychopathology such as post-traumatic stress disorder (PTSD). This investigation examined the association of PTSD and childhood maltreatment with three key HPA axis hormones: cortisol, dehydroepiandrosterone (DHEA), and dehydroepiandrosterone sulfate (DHEAS). Regression analyses were undertaken on a sample of 43 participants with and 57 participants without PTSD. Results demonstrated that after controlling for age, sex, and PTSD status, exposure to childhood maltreatment was significantly associated with cortisol secretion [F(4,95)=11.68, ΔR(2)=0.11, P=0.0009] and cortisol/DHEA ratio [F(4,95)=6.20, ΔR(2)=0.05, P=0.01]. PTSD status was not associated with any of these neuroendocrine variables. Findings are discussed in the context of the complexity of the relationship of these neuroendocrine variables with trauma exposure and trauma-related psychopathology. It is suggested that DHEA(S) or cortisol/DHEA(S) ratios may not be biomarkers of specific forms of psychopathology per se, but that, instead, the severity and developmental timing of trauma may set the HPA axis in ways that are reflected in interactions among these neuroendocrine hormones. In adulthood, these HPA axis hormones may continue to be dynamically affected by personal and environmental resources.

  3. Limited Diagnostic Utility of Plasma Adrenocorticotropic Hormone for Differentiation between Adrenal Cushing Syndrome and Cushing Disease.

    Science.gov (United States)

    Hong, A Ram; Kim, Jung Hee; Hong, Eun Shil; Kim, I Kyeong; Park, Kyeong Seon; Ahn, Chang Ho; Kim, Sang Wan; Shin, Chan Soo; Kim, Seong Yeon

    2015-09-01

    Measurement of the plasma adrenocorticotropic hormone (ACTH) level has been recommended as the first diagnostic test for differentiating between ACTH-independent Cushing syndrome (CS) and ACTH-dependent CS. When plasma ACTH values are inconclusive, a differential diagnosis of CS can be made based upon measurement of the serum dehydroepiandrosterone sulfate (DHEA-S) level and results of the high-dose dexamethasone suppression test (HDST). The aim of this study was to assess the utility of plasma ACTH to differentiate adrenal CS from Cushing' disease (CD) and compare it with that of the HDST results and serum DHEA-S level. We performed a retrospective, multicenter study from January 2000 to May 2012 involving 92 patients with endogenous CS. The levels of plasma ACTH, serum cortisol, 24-hour urine free cortisol (UFC) after the HDST, and serum DHEA-S were measured. Fifty-seven patients had adrenal CS and 35 patients had CD. The area under the curve of plasma ACTH, serum DHEA-S, percentage suppression of serum cortisol, and UFC after HDST were 0.954, 0.841, 0.950, and 0.997, respectively (all P<0.001). The cut-off values for plasma ACTH, percentage suppression of serum cortisol, and UFC after HDST were 5.3 pmol/L, 33.3%, and 61.6%, respectively. The sensitivity and specificity of plasma ACTH measurement were 84.2% and 94.3%, those of serum cortisol were 95.8% and 90.6%, and those of UFC after the HDST were 97.9% and 96.7%, respectively. Significant overlap in plasma ACTH levels was seen between patients with adrenal CS and those with CD. The HDST may be useful in differentiating between these forms of the disease, especially when the plasma ACTH level alone is not conclusive.

  4. The Relationship between Dehydroepiandrosterone (DHEA), Working Memory and Distraction – A Behavioral and Electrophysiological Approach

    Science.gov (United States)

    do Vale, Sónia; Selinger, Lenka; Martins, João Martin; Gomes, Ana Coelho; Bicho, Manuel; do Carmo, Isabel; Escera, Carles

    2014-01-01

    Dehydroepiandrosterone (DHEA) and dehydroepiandrosterone-sulphate (DHEAS) have been reported to have memory enhancement effects in humans. A neuro-stimulatory action and an anti-cortisol mechanism of action may contribute to that relation. In order to study DHEA, DHEAS and cortisol relations to working memory and distraction, we recorded the electroencephalogram of 23 young women performing a discrimination (no working memory load) or 1-back (working memory load) task in an audio-visual oddball paradigm. We measured salivary DHEA, DHEAS and cortisol both before each task and at 30 and 60 min. Under working memory load, a higher baseline cortisol/DHEA ratio was related to higher distraction as indexed by an enhanced novelty P3. This suggests that cortisol may lead to increased distraction whereas DHEA may hinder distraction by leading to less processing of the distractor. An increased DHEA production with consecutive cognitive tasks was found and higher DHEA responses attributed to working memory load were related to enhanced working memory processing as indexed by an enhanced visual P300. Overall, the results suggest that in women DHEA may oppose cortisol effects reducing distraction and that a higher DHEA response may enhance working memory at the electrophysiological level. PMID:25105970

  5. The relationship between dehydroepiandrosterone (DHEA, working memory and distraction--a behavioral and electrophysiological approach.

    Directory of Open Access Journals (Sweden)

    Sónia do Vale

    Full Text Available Dehydroepiandrosterone (DHEA and dehydroepiandrosterone-sulphate (DHEAS have been reported to have memory enhancement effects in humans. A neuro-stimulatory action and an anti-cortisol mechanism of action may contribute to that relation. In order to study DHEA, DHEAS and cortisol relations to working memory and distraction, we recorded the electroencephalogram of 23 young women performing a discrimination (no working memory load or 1-back (working memory load task in an audio-visual oddball paradigm. We measured salivary DHEA, DHEAS and cortisol both before each task and at 30 and 60 min. Under working memory load, a higher baseline cortisol/DHEA ratio was related to higher distraction as indexed by an enhanced novelty P3. This suggests that cortisol may lead to increased distraction whereas DHEA may hinder distraction by leading to less processing of the distractor. An increased DHEA production with consecutive cognitive tasks was found and higher DHEA responses attributed to working memory load were related to enhanced working memory processing as indexed by an enhanced visual P300. Overall, the results suggest that in women DHEA may oppose cortisol effects reducing distraction and that a higher DHEA response may enhance working memory at the electrophysiological level.

  6. The relationship between dehydroepiandrosterone (DHEA), working memory and distraction--a behavioral and electrophysiological approach.

    Science.gov (United States)

    do Vale, Sónia; Selinger, Lenka; Martins, João Martin; Gomes, Ana Coelho; Bicho, Manuel; do Carmo, Isabel; Escera, Carles

    2014-01-01

    Dehydroepiandrosterone (DHEA) and dehydroepiandrosterone-sulphate (DHEAS) have been reported to have memory enhancement effects in humans. A neuro-stimulatory action and an anti-cortisol mechanism of action may contribute to that relation. In order to study DHEA, DHEAS and cortisol relations to working memory and distraction, we recorded the electroencephalogram of 23 young women performing a discrimination (no working memory load) or 1-back (working memory load) task in an audio-visual oddball paradigm. We measured salivary DHEA, DHEAS and cortisol both before each task and at 30 and 60 min. Under working memory load, a higher baseline cortisol/DHEA ratio was related to higher distraction as indexed by an enhanced novelty P3. This suggests that cortisol may lead to increased distraction whereas DHEA may hinder distraction by leading to less processing of the distractor. An increased DHEA production with consecutive cognitive tasks was found and higher DHEA responses attributed to working memory load were related to enhanced working memory processing as indexed by an enhanced visual P300. Overall, the results suggest that in women DHEA may oppose cortisol effects reducing distraction and that a higher DHEA response may enhance working memory at the electrophysiological level.

  7. Novel dehydroepiandrosterone benzimidazolyl derivatives as 5α-reductase isozymes inhibitors.

    Science.gov (United States)

    Arellano, Yazmín; Bratoeff, Eugene; Segura, Tania; Mendoza, Maria Eugenia; Sánchez-Márquez, Araceli; Medina, Yesica; Heuze, Yvonne; Soriano, Juan; Cabeza, Marisa

    2016-12-01

    5α-R isozymes (types 1 and 2) play an important role in prostate gland development because they are responsible for intraprostatic dihydrotestosterone (DHT) levels when the physiological serum testosterone (T) concentration is low. In this study, we synthesized seven novel dehydroepiandrosterone derivatives with benzimidazol moiety at C-17, and determined their effect on the activity of 5α-reductase types 1 and 2. The derivatives with an aliphatic ester at C-3 of the dehydroepiandrosterone scaffold induced specific inhibition of 5α-R1 activity, whereas those with a cycloaliphatic ester (cyclopropyl, cyclobutyl, or cyclopentyl ring) or an alcohol group at C-3 inhibited the activity of both isozymes. Derivatives with a cyclohexyl or cycloheptyl ester at C-3 showed no inhibitory activity. In pharmacological experiments, derivatives with esters having an alcohol or the aliphatic group or one of the three smaller cycloaliphatic rings at C-3 decreased the diameter of male hamster flank organs, with the cyclobutyl and cyclopentyl esters exhibiting higher effect. With exception of the cyclobutyl and cyclopentyl esters, these compounds reduced the weight of the prostate and seminal vesicles.

  8. Syndecan heparan sulfate proteoglycans

    DEFF Research Database (Denmark)

    Gomes, Angélica Maciel; Sinkeviciute, Dovile; Multhaupt, Hinke A.B.

    2016-01-01

    Virtually all animal cells express heparan sulfate proteoglycans on the cell surface and in the extracellular matrix. Syndecans are a major group of transmembrane proteoglycans functioning as receptors that mediate signal transmission from the extracellular microenvironment to the cell. Their hep......Virtually all animal cells express heparan sulfate proteoglycans on the cell surface and in the extracellular matrix. Syndecans are a major group of transmembrane proteoglycans functioning as receptors that mediate signal transmission from the extracellular microenvironment to the cell....... Their heparan sulfate chains, due to their vast structural diversity, interact with a wide array of ligands including potent regulators of adhesion, migration, growth and survival. Frequently, ligands interact with cell surface heparan sulfate in conjunction with high affinity receptors. The consequent...... signaling can therefore be complex, but it is now known that syndecans are capable of independent signaling. This review is divided in two sections, and will first discuss how the assembly of heparan sulfate, the anabolic process, encodes information related to ligand binding and signaling. Second, we...

  9. Effects of dehydroepiandrosterone on fatigue and well-being in women with quiescent systemic lupus erythematosus : a randomised controlled trial

    NARCIS (Netherlands)

    Hartkamp, A.; Geenen, R.; Godaert, G. L. R.; Bijl, M.; Bijlsma, J. W. J.; Derksen, R. H. W. M.

    Objective Dehydroepiandrosterone (DHEA) has been reported to improve fatigue and reduced well-being. Both are major problems in patients with systemic lupus erythematosus (SLE), even with quiescent disease. Low serum DHEA levels are common in SLE. The present work investigates the effects of DHEA

  10. Dehydroepiandrosterone substitution in female adrenal failure: no impact on endothelial function and cardiovascular parameters despite normalization of androgen status

    DEFF Research Database (Denmark)

    Christiansen, Jens Juel; Andersen, Niels Holmark; Sørensen, Keld E

    2007-01-01

    BACKGROUND: Female adrenal insufficiency implicates reduced production of the adrenal androgen precursor dehydroepiandrosterone (DHEA) and low androgen levels. Oral DHEA restores androgen deficit but the clinical implications and safety of substitution therapy is uncertain. A putative DHEA receptor...... androgen levels using 6 months of DHEA replacement in this pilot study did not affect cardiovascular parameters and endothelial function in female adrenal insufficiency...

  11. Ovarian and Adrenal Androgens and Their Link to High Human Chorionic Gonadotropin Levels: A Prospective Controlled Study

    Directory of Open Access Journals (Sweden)

    René Rodríguez-Gutiérrez

    2014-01-01

    Full Text Available Background. Although the association between human chorionic gonadotropin (hCG and hyperandrogenism was identified more than 40 years ago, relevant questions remain unanswered. Design and Methods. We conducted a prospective, longitudinal, and controlled study in 23 women with a diagnosis of a complete hydatidiform mole (HM. Results. All participants completed the study. Before HM evacuation mean hCG was markedly higher in the cases than in the control group (P≤0.001. Free testosterone (T and dehydroepiandrosterone sulfate (DHEA-S were found to be higher in the cases (2.78 ± 1.24 pg/mL and 231.50 ± 127.20 μ/dL when compared to the control group (1.50 ± 0.75 pg/mL and 133.59 ± 60.69 μ/dL (P=0.0001 and 0.001, respectively. There was a strong correlation between hCG and free T/total T/DHEA-S concentrations (r=0.78; P≤0.001, r=0.74;  P≤0.001, and r=0.71;  P≤0.001, respectively. In the cases group 48 hours after HM evacuation, hCG levels were found to be significantly lower when compared to initial levels (P=0.001 and free T and DHEA-S declined significantly (P=0.0002 and 0.009. Conclusion. Before uterus evacuation, hCG, free T, and DHEA-S levels were significantly higher when compared with controls finding a strong correlation between hCG and free T/DHEA-S levels. Forty-eight hours after HM treatment hCG levels declined and the difference was lost. A novel finding of our study is that in cases, besides free T, DHEA-S was also found to be significantly higher and both the ovaries and adrenal glands appear to be the sites of this androgen overproduction.

  12. Liver X receptor alpha mediated genistein induction of human dehydroepiandrosterone sulfotransferase (hSULT2A1) in Hep G2 cells

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Yue; Zhang, Shunfen [Department of Physiological Sciences, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK 74078 (United States); Zhou, Tianyan [Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100083 (China); Huang, Chaoqun; McLaughlin, Alicia [Department of Physiological Sciences, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK 74078 (United States); Chen, Guangping, E-mail: guangping.chen@okstate.edu [Department of Physiological Sciences, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK 74078 (United States)

    2013-04-15

    Cytosolic sulfotransferases are one of the major families of phase II drug metabolizing enzymes. Sulfotransferase-catalyzed sulfonation regulates hormone activities, metabolizes drugs, detoxifies xenobiotics, and bioactivates carcinogens. Human dehydroepiandrosterone sulfotransferase (hSULT2A1) plays important biological roles by sulfating endogenous hydroxysteroids and exogenous xenobiotics. Genistein, mainly existing in soy food products, is a naturally occurring phytoestrogen with both chemopreventive and chemotherapeutic potential. Our previous studies have shown that genistein significantly induces hSULT2A1 in Hep G2 and Caco-2 cells. In this study, we investigated the roles of liver X receptor (LXRα) in the genistein induction of hSULT2A1. LXRs have been shown to induce expression of mouse Sult2a9 and hSULT2A1 gene. Our results demonstrate that LXRα mediates the genistein induction of hSULT2A1, supported by Western blot analysis results, hSULT2A1 promoter driven luciferase reporter gene assay results, and mRNA interference results. Chromatin immunoprecipitation (ChIP) assay results demonstrate that genistein increase the recruitment of hLXRα binding to the hSULT2A1 promoter. These results suggest that hLXRα plays an important role in the hSULT2A1 gene regulation. The biological functions of phytoestrogens may partially relate to their induction activity toward hydroxysteroid SULT. - Highlights: ► Liver X receptor α mediated genistein induction of hSULT2A1 in Hep G2 cells. ► LXRα and RXRα dimerization further activated this induction. ► Western blot results agreed well with luciferase reporter gene assay results. ► LXRs gene silencing significantly decreased hSULT2A1 expression. ► ChIP analysis suggested that genistein enhances hLXRα binding to the hSULT2A1 promoter.

  13. Dehydroepiandrosterone affects the expression of multiple genes in rat liver including 11 beta-hydroxysteroid dehydrogenase type 1: a cDNA array analysis.

    Science.gov (United States)

    Gu, Shi; Ripp, Sharon L; Prough, Russell A; Geoghegan, Thomas E

    2003-03-01

    Dehydroepiandrosterone (DHEA) is a C-19 adrenal steroid precursor to the gonadal steroids. In humans, circulating levels of DHEA, as its sulfated conjugate, are high at puberty and throughout early adulthood but decline with age. Dietary supplementation to maintain high levels of DHEA purportedly has beneficial effects on cognitive memory, the immune system, and fat and carbohydrate metabolism. In rodents, DHEA is a peroxisome proliferator that induces genes for the classical peroxisomal and microsomal enzymes associated with this response. These effects are mediated through activation of peroxisome proliferator-activated receptor alpha (PPAR alpha). However, DHEA can affect the expression of genes independently of PPAR alpha, including the gene for the major inducible drug and xenobiotic metabolizing enzyme, cytochrome P450 3A23. To elucidate the biochemistry associated with DHEA treatment, we employed a cDNA gene expression array using liver RNA from rats treated with DHEA or the classic peroxisome proliferator nafenopin. Principal components analysis identified 30 to 35 genes whose expression was affected by DHEA and/or nafenopin. Some were genes previously identified as PPAR-responsive genes. Changes in expression of several affected genes were verified by quantitative reverse transcriptase-polymerase chain reaction. These included aquaporin 3, which was induced by DHEA and to a lesser extent nafenopin, nuclear tyrosine phosphatase, which was induced by both agents, and 11 beta-hydroxysteroid dehydrogenase 1, which was decreased by treatment with DHEA in a dose-dependent fashion. Regulation of 11 beta-hydroxysteroid dehydrogenase 1 expression is important since the enzyme is believed to amplify local glucocorticoid signaling, and its repression may cause some of the metabolic effects associated with DHEA.

  14. Biotransformation of dehydroepiandrosterone with Macrophomina phaseolina and β-glucuronidase inhibitory activity of transformed products.

    Science.gov (United States)

    Choudhary, M Iqbal; Zafar, Salman; Khan, Naik Tameen; Ahmad, Saeed; Noreen, Shagufta; Marasini, Bishnu P; Al-Khedhairy, Abdulaziz A; Atta-Ur-Rahman

    2012-06-01

    The biotransformation of dehydroepiandrosterone (1) with Macrophomina phaseolina was investigated. A total of eight metabolites were obtained which were characterized as androstane-3,17-dione (2), androst-4-ene-3,17-dione (3), androst-4-ene-17β-ol-3-one (4), androst-4,6-diene-17β-ol-3-one (5), androst-5-ene-3β,17β-diol (6), androst-4-ene-3β-ol-6,17-dione (7), androst-4-ene-3β,7β,17β-triol (8), and androst-5-ene-3β,7α,17β-triol (9). All the transformed products were screened for enzyme inhibition, among which four were found to inhibit the β-glucuronidase enzyme, while none inhibited the α-chymotrypsin enzyme.

  15. Trypanosoma cruzi: dehydroepiandrosterone (DHEA) and immune response during the chronic phase of the experimental Chagas' disease.

    Science.gov (United States)

    Caetano, Leony Cristina; Santello, Fabricia Helena; Del Vecchio Filipin, Marina; Brazão, Vânia; Caetano, Luana Naiara; Toldo, Miriam Paula Alonso; Caldeira, Jerri C; do Prado Júnior, José Clóvis

    2009-07-07

    Dehydroepiandrosterone (DHEA) has long been considered as a precursor for many steroid hormones. It also enhances the immune responses against a wide range of viral, bacterial, and parasitic pathogens. The aims of this work were to evaluate the influences of exogenous DHEA treatment on Wistar rats infected with the Y strain of Trypanosoma cruzi during the acute and its influence on the chronic phase of infection. Animals were subcutaneous treated with 40 mg/kg body weight/day of DHEA. DHEA treatment promoted increased lymphoproliferative responses as well as enhanced concentrations of NO and IL-12. So, we point in the direction that our results validate the utility of the use of DHEA as an alternative therapy candidate against T. cruzi.

  16. Dehydroepiandrosterone inhibits the spontaneous release of superoxide radical by alveolar macrophages in vitro in asbestosis

    Energy Technology Data Exchange (ETDEWEB)

    Rom, W.N.; Harkin, T. (New York Univ. Medical Center, New York (United States))

    1991-08-01

    Asbestosis is characterized by an alveolar macrophage alveolitis with injury and fibrosis of the lower respiratory tract. Alveolar macrophages recovered by bronchoalveolar lavage spontaneously release exaggerated amounts of oxidants including superoxide anion and hydrogen peroxide that may mediate alveolar epithelial cell injury. Dehydroepiandrosterone (DHEA) is a normally occurring adrenal androgen that inhibits glucose-6-phosphate dehydrogenase, the initial enzyme in the pentose phosphate shunt necessary for NADPH generation and superoxide anion formation. In this regard, the authors hypothesized that DHEA may reduce asbestos-induced oxidant release. DHEA added in vitro to alveolar macrophages lavaged from 11 nonsmoking asbestos workers significantly reduced superoxide anion release. DHEA is an antioxidant and potential anticarcinogenic agent that may have a therapeutic role in reducing the increased oxidant burden in asbestos-induced alveolitis of the lower respiratory tract.

  17. Influence of acute and subchronic oral administration of dehydroepiandrosterone (DHEA) on nociceptive threshold in rats.

    Science.gov (United States)

    Gąsińska, Emilia; Bujalska-Zadrożny, Magdalena; Sar, Monika; Makulska-Nowak, Helena

    2012-01-01

    Dehydroepiandrosterone (DHEA), a neurosteroid, is known to be the most abundant hormone in the human body. Its role in the central nervous system has not been well defined. Previous studies indicate that DHEA is synthesized in the spinal cord and plays an important role in pain modulation. In the present study, we investigated the effect of DHEA on pain threshold in rats after both acute and subchronic treatment. Rats were orally administered with DHEA at a dose of 10 mg/kg once daily and the pain threshold was measured with mechanical and thermal stimuli. After acute treatment, DHEA exhibited pronociceptive effects which lasted up to 150 min. After subchronic administration, DHEA showed an opposite effect by elevating the pain threshold. The results suggest that DHEA could be indicated as a drug to improve treatment of chronic pain disorders.

  18. Dehydroepiandrosterone (DHEA) replacement decreases insulin resistance and lowers inflammatory cytokines in aging humans.

    Science.gov (United States)

    Weiss, Edward P; Villareal, Dennis T; Fontana, Luigi; Han, Dong-Ho; Holloszy, John O

    2011-05-01

    Plasma dehydroepiandrosterone (DHEA) decreases ~80% between ages 25 and 75 yr. In a preliminary study, we found that 6 mo of DHEA replacement improved insulin action in elderly individuals. The purpose of the present larger, randomized double-blind study was to determine whether a longer period of DHEA replacement improves glucose tolerance. Fifty-seven men and 68 women aged 65 to 75 yr were randomly assigned to 50 mg DHEA or placebo once daily. Year one was a randomized, double blind trial. Year 2 was an open label continuation. DHEA replacement improved glucose tolerance in participants who had abnormal GT initially, reduced plasma triglycerides, and the inflammatory cytokines IL6 and TNFα.

  19. The effect of dehydroepiandrosterone (DHEA) on recognition memory decision processes and discrimination in postmenopausal women.

    Science.gov (United States)

    Hirshman, Elliot; Wells, Ellen; Wierman, Margaret E; Anderson, Benjamin; Butler, Andrew; Senholzi, Meredith; Fisher, Julia

    2003-03-01

    In this article, the theoretical distinction between recognition memory decision and discrimination processes is used to explore the effect of dehydroepiandrosterone (DHEA) in postmenopausal women. DHEA is an adrenal steroid that diminishes with aging. It has enhanced memory in laboratory animals. An 8-week placebo-controlled, double-blind experiment in which 30 women (ages 39-70) received a 50-mg/day oral dose of DHEA for 4 weeks demonstrated that DHEA made subjects more conservative (i.e., less likely to call test items "old") in their recognition memory decisions and enhanced recognition memory discrimination for items presented briefly. The former result may reflect an empirical regularity (Hirshman, 1995) in which recent strong memory experiences make participants more conservative. The latter result may reflect the effect of DHEA on visual perception, with consequent effects on memory. These results suggest the methodological importance of focusing on decision processes when examining the effects of hormones on memory.

  20. Peptidomimetics Based On Dehydroepiandrosterone Scaffold: Synthesis, Antiproliferation Activity, Structure-Activity Relationship, and Mechanisms

    Science.gov (United States)

    Wang, Xiaohui; Su, Haihuan; Wang, Wenda; Chen, Changshui; Cao, Xiufang

    2016-09-01

    A series of novel peptidomimetics bearing dehydroepiandrosterone moiety were designed, synthesized, and evaluated for their inhibition activities against cell proliferation. According to the preliminary studies on inhibitory activities, some of the newly prepared compounds indicated significantly inhibition activities against human hepatoma cancer (HepG2), human lung cancer (A549), human melanoma (A875) cell lines compared with the control 5-fluorouracil. Especially, compounds Ii (IC50 IC50 < 13 μM) exhibited obvious inhibition activities against all tested cell lines. The highly potential compound Ik induced apoptosis in HepG2 cells were analyzed by flow cytometry, and the apoptotic effects of compound Ik were further evaluated using Annexin V-FITC/propidium iodide dual staining assay, which revealed these highly potential compounds induced cell death in HepG2 cells at least partly by apoptosis.

  1. Controlling barium sulfate

    Energy Technology Data Exchange (ETDEWEB)

    Greenley, R.

    Even though for several years success has been realized in controlling barium sulfate scale deposition in relatively shallow, low pressure oil wells--by squeezing an organic phosphonate scale inhibitor into the producing zone--barium sulfate scale depositon in deep, high pressure/high temperature wells usually meant an expensive workover operation. A case history of a deep (16,000 ft) well in St. Mary Parish, Louisiana, and the scale inhibitor squeeze operation are described. Based on the successful results obtained in treating this well, a generalized treating procedure for combating downhole scale deposition in high pressure/high temperature gas wells is presented. Formation squeezing with such an inhibitor represents a significant breakthrough for the oil and gas industry.

  2. Sulfation of chondroitin. Specificity, degree of sulfation, and detergent effects with 4-sulfating and 6-sulfating microsomal systems

    Energy Technology Data Exchange (ETDEWEB)

    Sugumaran, G.; Silbert, J.E.

    1988-04-05

    Microsomal preparations from chondroitin 6-sulfate-producing chick embryo epiphyseal cartilage, and from chondroitin 4-sulfate-producing mouse mastocytoma cells, were incubated with UDP-(14C)glucuronic acid and UDP-N-acetylgalactosamine to form non-sulfated proteo(14C)chondroitin. Aliquots of the incubations were then incubated with 3'-phosphoadenylylphosphosulfate (PAPS) in the presence or absence of various detergents. In the absence of detergents, there was good sulfation of this endogenous proteo(14C)chondroitin by the original microsomes from both sources. Detergents, with the exception of Triton X-100, markedly inhibited sulfation in the mast cell system but not in the chick cartilage system. These results indicate that sulfation and polymerization are closely linked on cell membranes and that in some cases this organization can be disrupted by detergents. When aliquots of the original incubation were heat inactivated, and then reincubated with new microsomes from chick cartilage and/or mouse mastocytoma cells plus PAPS, there was no significant sulfation of this exogenous proteo(14C) chondroitin with either system unless Triton X-100 was added. Sulfation of exogenous chondroitin and chondroitin hexasaccharide was compared with sulfation of endogenous and exogenous proteo(14C)chondroitin. Sulfate incorporation into hexasaccharide and chondroitin decreased as their concentrations (based on uronic acid) approached that of the proteo(14C)chondroitin. At the same time, the degree of sulfation in percent of substituted hexosamine increased. However, the degree of sulfation did not reach that of the endogenous proteo(14C)chondroitin. Hexasaccharide and chondroitin sulfation were stimulated by the presence of Triton X-100. However, in contrast to the exogenous proteo(14C)chondroitin, there was some sulfation of hexasaccharide and chondroitin in the absence of this detergent.

  3. Off limits: sulfate below the sulfate-methane transition

    Science.gov (United States)

    Brunner, Benjamin; Arnold, Gail; Røy, Hans; Müller, Inigo; Jørgensen, Bo

    2016-07-01

    One of the most intriguing recent discoveries in biogeochemistry is the ubiquity of cryptic sulfur cycling. From subglacial lakes to marine oxygen minimum zones, and in marine sediments, cryptic sulfur cycling - the simultaneous sulfate consumption and production - has been observed. Though this process does not leave an imprint in the sulfur budget of the ambient environment - thus the term cryptic - it may have a massive impact on other element cycles and fundamentally change our understanding of biogeochemical processes in the subsurface. Classically, the sulfate-methane transition (SMT) in marine sediments is considered to be the boundary that delimits sulfate reduction from methanogenesis as the predominant terminal pathway of organic matter mineralization. Two sediment cores from Aarhus Bay, Denmark reveal the constant presence of sulfate (generally 0.1 to 0.2 mM) below the SMT. The sulfur and oxygen isotope signature of this deep sulfate (34S = 18.9‰, 18O = 7.7‰) was close to the isotope signature of bottom-seawater collected from the sampling site (34S = 19.8‰, 18O = 7.3‰). In one of the cores, oxygen isotope values of sulfate at the transition from the base of the SMT to the deep sulfate pool (18O = 4.5‰ to 6.8‰) were distinctly lighter than the deep sulfate pool. Our findings are consistent with a scenario where sulfate enriched in 34S and 18O is removed at the base of the SMT and replaced with isotopically light sulfate below. Here, we explore scenarios that explain this observation, ranging from sampling artifacts, such as contamination with seawater or auto-oxidation of sulfide - to the potential of sulfate generation in a section of the sediment column where sulfate is expected to be absent which enables reductive sulfur cycling, creating the conditions under which sulfate respiration can persist in the methanic zone.

  4. Dehydroepiandrosterone (DHEA) inhibition of monocyte binding by vascular endothelium is associated with sialylation of neural cell adhesion molecule.

    Science.gov (United States)

    Curatola, Anna-Maria; Huang, Kui; Naftolin, Frederick

    2012-01-01

    Adhesion of monocytes to vascular endothelium is necessary for atheroma formation. This adhesion requires binding of endothelial neural cell adhesion molecule (NCAM) to monocyte NCAM. NCAM:NCAM binding is blocked by sialylation of NCAM (polysialylated NCAM; PSA-NCAM). Since estradiol (E2) and dihydrotestosterone (DHT) induced PSA-NCAM and decreased monocyte adhesion, in consideration of possible clinical applications we tested whether their prohormone dehydroepiandrosterone (DHEA) has similar effects. (1) DHEA was administered to cultured human coronary artery endothelial cells (HCAECs) from men and women. Monocyte binding was assessed using fluorescence-labeled monocytes. (2) HCEACs were incubated with E2, DHT, DHEA alone, or with trilostane, fulvestrant or flutamide. Expression of PSA-NCAM was assessed by immunohistochemistry and Western blotting. Dehydroepiandrosterone inhibited monocyte adhesion to HCAECs by ≥50% (P DHEA's inhibition of monocyte binding appeared to be gender dependent. The DHEA-induced expression of PSA-NCAM was completely blocked by trilostane. In these preliminary in vitro studies, DHEA increased PSA-NCAM expression and inhibited monocyte binding in an estrogen- and androgen receptor-dependent manner. Dehydroepiandrosteroneappears to act via its end metabolites, E2 and DHT. Dehydroepiandrosterone could furnish clinical prevention against atherogenesis and arteriosclerosis.

  5. 2-Amino-4-hydroxyethylaminoanisole sulfate

    DEFF Research Database (Denmark)

    Madsen, Jakob T; Andersen, Klaus E

    2016-01-01

    positive patch test reactions to the coupler 2-amino-4-hydroxyethylaminoanisole sulfate 2% pet. from 2005 to 2014. METHODS: Patch test results from the Allergen Bank database for eczema patients patch tested with 2-amino-4-hydroxyethylaminoanisole sulfate 2% pet. from 2005 to 2014 were reviewed. RESULTS......: A total of 902 dermatitis patients (154 from the dermatology department and 748 from 65 practices) were patch tested with amino-4-hydroxyethylaminoanisole sulfate 2% pet. from 2005 to 2014. Thirteen (1.4%) patients had a positive patch test reaction. Our results do not indicate irritant reactions....... CONCLUSIONS: 2-Amino-4-hydroxyethylaminoanisole sulfate is a new but rare contact allergen....

  6. 21 CFR 184.1315 - Ferrous sulfate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Ferrous sulfate. 184.1315 Section 184.1315 Food and... Substances Affirmed as GRAS § 184.1315 Ferrous sulfate. (a) Ferrous sulfate heptahydrate (iron (II) sulfate... as pale, bluish-green crystals or granules. Progressive heating of ferrous sulfate heptahydrate...

  7. The neurosteroids allopregnanolone and dehydroepiandrosterone modulate resting-state amygdala connectivity.

    Science.gov (United States)

    Sripada, Rebecca K; Welsh, Robert C; Marx, Christine E; Liberzon, Israel

    2014-07-01

    The neurosteroids allopregnanolone and dehydroepiandrosterone (DHEA) are integral components of the stress response and exert positive modulatory effects on emotion in both human and animal studies. Although these antidepressant and anxiolytic effects have been well established, to date, little research has examined their neural correlates, and no research has been conducted into the effects of neurosteroids on large-scale networks at rest. To investigate the neurosteroid impact on intrinsic connectivity networks, participants were administered 400 mg of pregnenolone (N = 16), 400 mg of DHEA (N = 14), or placebo (N = 15) and underwent 3T fMRI. Resting-state brain connectivity was measured using amygdala as a seed region. When compared with placebo, pregnenolone administration reduced connectivity between amygdala and dorsal medial prefrontal cortex, between amygdala and precuneus, and between amygdala and hippocampus. DHEA reduced connectivity between amygdala and periamygdala and between amygdala and insula. Reductions in amygdala to precuneus connectivity were associated with less self-reported negative affect. These results demonstrate that neurosteroids modulate amygdala functional connectivity during resting state and may be a target for pharmacological intervention. Additionally, allopregnanolone and DHEA may shift the balance between salience network and default network, a finding that could provide insight into the neurocircuitry of anxiety psychopathology.

  8. Dehydroepiandrosterone and metyrapone partially restore the adaptive humoral and cellular immune response in endotoxin immunosuppressed mice.

    Science.gov (United States)

    Rearte, Bárbara; Maglioco, Andrea; Machuca, Damián; Greco, Daiana Martire; Landoni, Verónica I; Rodriguez-Rodrigues, Nahuel; Meiss, Roberto; Fernández, Gabriela C; Isturiz, Martín A

    2014-08-01

    Prior exposure to endotoxins renders the host temporarily refractory to subsequent endotoxin challenge (endotoxin tolerance). Clinically, this state has also been pointed out as the initial cause of the non-specific humoral and cellular immunosuppression described in these patients. We recently demonstrated the restoration of immune response with mifepristone (RU486), a receptor antagonist of glucocorticoids. Here we report the treatment with other modulators of glucocorticoids, i.e. dehydroepiandrosterone (DHEA), a hormone with anti-glucocorticoid properties, or metyrapone (MET) an inhibitor of corticosterone synthesis. These drugs were able to partially, but significantly, restore the humoral immune response in immunosuppressed mice. A significant recovery of proliferative responsiveness was also observed when splenocytes were obtained from DHEA- or MET-treated immunosuppressed mice. In addition, these treatments restored the hypersensitivity response in immunosuppressed mice. Finally, although neither DHEA nor MET improved the reduced CD4 lymphocyte count in spleen from immunosuppressed mice, both treatments promoted spleen architecture reorganization, partially restoring the distinct cellular components and their localization in the spleen. The results from this study indicate that DHEA and MET could play an important role in the restoration of both adaptive humoral and cellular immune response in LPS-immunosuppressed mice, reinforcing the concept of a central involvement of endogenous glucocorticoids on this phenomenon. © The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  9. Administration of dehydroepiandrosterone (DHEA) enhances visual-spatial performance in postmenopausal women.

    Science.gov (United States)

    Stangl, Bethany; Hirshman, Elliot; Verbalis, Joseph

    2011-10-01

    The current article examines the effect of administering dehydroepiandrosterone (DHEA) on visual-spatial performance in postmenopausal women (N = 24, ages 55-80). The concurrent reduction of serum DHEA levels and visual-spatial performance in this population, coupled with the documented effects of DHEA's androgenic metabolites on visual-spatial performance, suggests that DHEA administration may enhance visual-spatial performance. The current experiment used a double-blind, placebo-controlled crossover design in which 50 mg of oral DHEA was administered daily in the drug condition to explore this hypothesis. Performance on the Mental Rotation, Subject-Ordered Pointing, Fragmented Picture Identification, Perceptual Identification, Same-Different Judgment, and Visual Search tasks and serum levels of DHEA, DHEAS, testosterone, estrone, and cortisol were measured in the DHEA and placebo conditions. In contrast to prior experiments using the current methodology that did not demonstrate effects of DHEA administration on episodic and short-term memory tasks, the current experiment demonstrated large beneficial effects of DHEA administration on Mental Rotation, Subject-Ordered Pointing, Fragmented Picture Identification, Perceptual Identification, and Same-Different Judgment. Moreover, DHEA administration enhanced serum levels of DHEA, DHEAS, testosterone, and estrone, and regression analyses demonstrated that levels of DHEA and its metabolites were positively related to cognitive performance on the visual-spatial tasks in the DHEA condition.

  10. Effect of competitional stress on salivary dehydroepiandrosterone, cortisol in female handballists

    Directory of Open Access Journals (Sweden)

    Parvin Farzanegi

    2010-11-01

    Full Text Available Background: Hormonal responses to competitions and their relationships have been extensively examined in male athletes, but there are few studies in women. The purpose of this study was to determine the effects of competition stress on salivary dehydroepiandrosterone (DHEA and cortisol in female handballists. Materials and Method: Ten female handballists of Islamic Azad University (Sari Branch (age 21.5±2.5 years participated in this study. Salivary samples were collected 30 min and 5 min before competition, between two half times and immediately after four competitions. The salivary DHEA and cortisol concentrations were measured by ELISA method. Results: The results of one-way ANOVA with repeated measures have shown a significant (p=0.001 increases for DHEA concentration after four competitions, however, cortisol and DHEA/cortisol ratio did not show any changes after four competition (p>0.05. Conclusion: These results indicate that salivary DHEA is more sensitive to competition situations than cortisol concentration. We suggested that androgens maybe more affected by competition

  11. Effects of dehydroepiandrosterone (DHEA) and lactate on glucose uptake in the central nervous system.

    Science.gov (United States)

    de Souza, Danielle Kaiser; Ribeiro, Maria Flávia Marques; Kucharski, Luiz Carlos Rios

    2012-01-17

    Dehydroepiandrosterone (DHEA) prevents brain aging, enhances the cerebral metabolism and interacts with energy substrates. The interaction between lactate and DHEA on glucose uptake and lactate oxidation by various nervous structures was investigated and results demonstrate that the 2-(14)C-deoxiglucose (2-(14)C-Dglucose) uptake was stimulated by 10mM lactate in the hypothalamus and olfactory bulb, inhibited in the cerebral cortex and cerebellum, and unaffected in the hippocampus. We also show that, in both the cerebral cortex and hypothalamus, (14)C-lactate oxidation was higher than (14)C-glucose oxidation (p≤0.001), demonstrating a relevant role for lactate as energy substrate. The interaction of lactate and 10(-8)M DHEA was tested and, although DHEA had no significant effect on uptake in the cerebellum, hippocampus, or hypothalamus, 10(-8)M DHEA increased the 2-(14)C-Dglucose uptake in the cerebral cortex in the presence of lactate (p≤0.001), and in the olfactory bulb in the absence of lactate (pDHEA had no significant effect on (14)C-lactate oxidation. We suggest that DHEA improves glucose uptake in specific conditions. Thus, DHEA may affect CNS metabolism and interact with lactate, which is the most important neuronal energy substrate, on glucose uptake. Crown Copyright © 2011. Published by Elsevier Ireland Ltd. All rights reserved.

  12. Administration of Dehydroepiandrosterone (DHEA) Enhances Visual-Spatial Performance in Post-Menopausal Women

    Science.gov (United States)

    Stangl, Bethany; Hirshman, Elliot; Verbalis, Joseph

    2013-01-01

    The current paper examines the effect of administering Dehydroepiandrosterone (DHEA) on visual-spatial performance in post-menopausal women (N=24, ages 55-80). The concurrent reduction of serum DHEA levels and visual-spatial performance in this population, coupled with the documented effects of DHEA’s androgenic metabolites on visual-spatial performance, suggest that DHEA administration may enhance visual-spatial performance. The current experiment used a double-blind placebo-controlled crossover design in which 50 mg of oral DHEA was administered daily in the drug condition to explore this hypothesis. Performance on the Mental Rotation, Subject-Ordered Pointing, Fragmented Picture Identification, Perceptual Identification, Same-Different Judgment, and Visual Search tasks and serum levels of DHEA, DHEAS, testosterone, estrone and cortisol were measured in the DHEA and placebo conditions. In contrast to prior experiments using the current methodology that did not demonstrate effects of DHEA administration on episodic and short-term memory tasks, the current experiment demonstrated large beneficial effects of DHEA administration on Mental Rotation, Subject-Ordered Pointing, Fragmented Picture Identification, Perceptual Identification and Same-Different Judgment. Moreover, DHEA administration enhanced serum levels of DHEA, DHEAS, testosterone and estrone, and regression analyses demonstrated that levels of DHEA and its metabolites were positively related to cognitive performance on the visual-spatial tasks in the DHEA condition PMID:21942436

  13. Diurnal and stress-reactive dehydroepiandrosterone levels and telomere length in youth

    Directory of Open Access Journals (Sweden)

    Andrew R Dismukes

    2016-05-01

    Full Text Available The current investigation examined the association between the aging-related biomarkers dehydroepiandrosterone (DHEA and telomere length (TL in community-recruited African-American youth. The examination of DHEA included stress reactive, basal and diurnal sampling, in order to elucidate the underlying physiological process that may overlap with TL. One hundred and two participants completed the Trier Social Stressor Test for children (TSST-C. TL was obtained from all youth from buccal swabs on the same day as the TSST-C. Saliva samples from 83 participants were obtained over the course of two additional days to measure waking and diurnal levels of DHEA. DHEA diurnal slope was a robust predictor of TL (B=0.516, P<0.05, while other DHEA values were not significantly associated with TL. This study is one of the first studies to examine basal, diurnal and reactivity measurements of DHEA in youth. Furthermore, this is the first study, to our knowledge, to demonstrate a positive association between DHEA, a putative anti-aging hormone, and TL, an indicator of cellular aging.

  14. Dehydroepiandrosterone (DHEA) improves pulmonary hypertension in chronic obstructive pulmonary disease (COPD): a pilot study.

    Science.gov (United States)

    Dumas de La Roque, Eric; Savineau, Jean-Pierre; Metivier, Anne-Cécile; Billes, Marc-Alain; Kraemer, Jean-Philippe; Doutreleau, Stéphane; Jougon, Jacques; Marthan, Roger; Moore, Nicholas; Fayon, Michael; Baulieu, Etienne-Émile; Dromer, Claire

    2012-02-01

    It was previously shown that dehydroepiandrosterone (DHEA) reverses chronic hypoxia-induced pulmonary hypertension (PH) in rats, but whether DHEA can improve the clinical and hemodynamic status of patients with PH associated to chronic obstructive pulmonary disease (PH-COPD) has not been studied whereas it is a very severe poorly treated disease. Eight patients with PH-COPD were treated with DHEA (200mg daily orally) for 3 months. The primary end-point was the change in the 6-minute walk test (6-MWT) distance. Secondary end-points included pulmonary hemodynamics, lung function tests and tolerance of treatment. The 6-MWT increased in all cases, from 333m (median [IQR]) (257; 378) to 390m (362; 440) (PDHEA treatment did not change respiratory parameters of gas exchange and the 200mg per day of DHEA used was perfectly tolerated with no side effect reported. DHEA treatment significantly improves 6-MWT distance, pulmonary hemodynamics and DLCO of patients with PH-COPD, without worsening gas exchange, as do other pharmacological treatments of PH (trial registration NCT00581087). Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  15. Neuroprotective effects of dehydroepiandrosterone (DHEA) in rat model of Alzheimer's disease.

    Science.gov (United States)

    Aly, Hanan F; Metwally, Fateheya M; Ahmed, Hanaa H

    2011-01-01

    The current study was undertaken to elucidate a possible neuroprotective role of dehydroepiandrosterone (DHEA) against the development of Alzheimer's disease in experimental rat model. Alzheimer's disease was produced in young female ovariectomized rats by intraperitoneal administration of AlCl(3) (4.2 mg/kg body weight) daily for 12 weeks. Half of these animals also received orally DHEA (250 mg/kg body weight, three times weekly) for 18 weeks. Control groups of animals received either DHAE alone, or no DHEA, or were not ovariectomized. After such treatment the animals were analyzed for oxidative stress biomarkers such as hydrogen peroxide, nitric oxide and malondialdehyde, total antioxidant capacity, reduced glutathione, glutathione peroxidase, glutathione reductase, superoxide dismutase and catalase activities, antiapoptotic marker Bcl-2 and brain derived neurotrophic factor. Also brain cholinergic markers (acetylcholinesterase and acetylcholine) were determined. The results revealed significant increase in oxidative stress parameters associated with significant decrease in the antioxidant enzyme activities in Al-intoxicated ovariectomized rats. Significant depletion in brain Bcl-2 and brain-derived neurotrophic factor levels were also detected. Moreover, significant elevations in brain acetylcholinesterase activity accompanied with significant reduction in acetylcholine level were recorded. Significant amelioration in all investigated parameters was detected as a result of treatment of Al-intoxicated ovariectomized rats with DHEA. These results were confirmed by histological examination of brain sections. These results clearly indicate a neuroprotective effect of DHEA against Alzheimer's disease.

  16. Relationship between salivary levels of cortisol and dehydroepiandrosterone levels in saliva and chronic periodontitis

    Directory of Open Access Journals (Sweden)

    Siddhi Mudrika

    2014-01-01

    Full Text Available Aim: The aim was to investigate the association between cortisol and dehydroepiandrosterone (DHEA levels in patients with periodontitis and healthy controls. Materials and Methods: Cortisol and DHEA levels in saliva were determined in 20 subjects, with clinical examinations including oral hygiene index, sulcus bleeding index (Muhlemann and Son and probing depth was also performed. Statistical Analysis: Data were analyzed with the help of SPSS software package (version 7.0, and the significance level was set at 95% confidence interval. Mann-Whitney test and t-test were used to see the correlation between the groups. Results: In cortisol and DHEA the mean and standard deviation of periodontitis group were (2.6 ± 0.37 and (66.7 ± 8.7 respectively. Conclusion: This shows there is an increase in the mean value of cortisol and DHEA in periodontitis than the control group. Salivary cortisol and DHEA level were found to be increased in concordance with disease severity. This was statistically significant with P < 0.001.

  17. Dehydroepiandrosterone (DHEA) reduces embryo aneuploidy: direct evidence from preimplantation genetic screening (PGS).

    Science.gov (United States)

    Gleicher, Norbert; Weghofer, Andrea; Barad, David H

    2010-11-10

    Dehydroepiandrosterone (DHEA) has been reported to improve pregnancy chances in women with diminished ovarian reserve (DOR), and to reduce miscarriage rates by 50-80%. Such an effect is mathematically inconceivable without beneficial effects on embryo ploidy. This study, therefore, assesses effects of DHEA on embryo aneuploidy. In a 1:2, matched case control study 22 consecutive women with DOR, supplemented with DHEA, underwent preimplantation genetic screening (PGS) of embryos during in vitro fertilization (IVF) cycles. Each was matched by patient age and time period of IVF with two control IVF cycles without DHEA supplementation (n = 44). PGS was performed for chromosomes X, Y, 13, 16, 18, 21 and 22, and involved determination of numbers and percentages of aneuploid embryos. DHEA supplementation to a significant degree reduced number (P = 0.029) and percentages (P DHEA effects on DOR patients, at least partially, are the likely consequence of lower embryo aneuploidy. DHEA supplementation also deserves investigation in older fertile women, attempting to conceive, where a similar effect, potentially, could positively affect public health.

  18. Dehydroepiandrosterone (DHEA) protects hippocampal cells from oxidative stress-induced damage.

    Science.gov (United States)

    Bastianetto, S; Ramassamy, C; Poirier, J; Quirion, R

    1999-03-20

    It has been postulated that decreases in plasma levels of dehydroepiandrosterone (DHEA) may contribute to the development of some age-related disorders. Along with neuroprotective and memory enhancing effects, DHEA has been shown to display antioxidant properties. Moreover, oxidative stress is known to cause lipid peroxidation and degenerative changes in the hippocampus, an area involved in memory processes and especially afflicted in Alzheimer's disease (AD). Accordingly, we investigated the antioxidant effects of DHEA in models of oxidative stress using rat primary hippocampal cells and human hippocampal tissue from AD patients and age-matched controls. A pre-treatment of rat primary mixed hippocampal cell cultures with DHEA (10-100 microM) protected against the toxicity induced by H2O2 and sodium nitroprusside. Moreover, DHEA (10-100 microM) was also able to prevent H2O2/FeSO4-stimulated lipid oxidation in both control and AD hippocampal tissues. Taken together, these data suggest that DHEA may be useful in treating age-related central nervous system diseases based on its protective effects in the hippocampus. Copyright 1999 Elsevier Science B.V.

  19. Dehydroepiandrosterone increases synaptosomal glutamate release and improves the performance in inhibitory avoidance task.

    Science.gov (United States)

    Lhullier, F L R; Nicolaidis, R; Riera, N G; Cipriani, F; Junqueira, D; Dahm, K C S; Brusque, A M; Souza, D O

    2004-03-01

    Dehydroepiandrosterone (DHEA) exerts multiple effects in the rodent central nervous system (CNS), mediated through its nongenomic actions on several neurotransmitter systems, increasing neuronal excitability, modulating neuronal plasticity and presenting neuroprotective properties. It has been demonstrated that DHEA is a potent modulator of GABA(A), NMDA and Sigma receptors. In the present study, we investigated the effect of DHEA on (i) basal- and K(+)-stimulated l-[(3)H]glutamate release from synaptosomes (both in vitro and ex vivo), (ii) synaptosomal l-[(3)H]glutamate uptake (in vitro), and (iii) an inhibitory avoidance task (in vivo). The results indicated that DHEA in vitro increased glutamate release by 57%, and its intracerebroventricular infusion increased the basal-[(3)H]glutamate release by 15%. After 30 min of intraperitoneal administration, DHEA levels in the serum or CSF increased 33 and 21 times, respectively. Additionally, DHEA, intraperitoneally administrated 30 min before training, improved memory for inhibitory avoidance task. Concluding, DHEA could improve memory on an inhibitory avoidance task, perhaps due to its ability to physiologically strength the glutamatergic tonus by increasing glutamate release.

  20. Selective conversion by microglia of dehydroepiandrosterone to 5-androstenediol-A steroid with inherent estrogenic properties.

    Science.gov (United States)

    Jellinck, Peter H; Kaufmann, Martin; Gottfried-Blackmore, Andres; McEwen, Bruce S; Jones, Glenville; Bulloch, Karen

    2007-01-01

    The well-established neuroprotective effect of dehydroepiandrosterone (DHEA) has been attributed to its metabolism in the brain to provide estrogens known to be neuroprotective and to enhance memory and learning in humans and animals. However, our previous work showed that the conversion of DHEA to 4-androstenedione (AD), the precursor of estrone (E(1)) and estradiol (E(2)), is very low in several different types of neural cells, and that the main product is 7alpha-hydroxy-DHEA (7alpha-OH-DHEA). In this study, we found that microglia are an exception and produce mainly 5-androstene-3beta,17beta-diol (Delta(5)-Adiol), a C(19) steroid with estrogen-like activity from DHEA. Virtually, no other products, including testosterone (T) were detected by TLC or HPLC in incubations of (3)H-labeled DHEA with the BV2 microglial cell line. Microglia are important brain cells that are thought to play a house-keeping role during the steady state, and that are crucial to the brain's immune reaction to injury and the healing process. Our findings suggest that the microglia-produced Delta(5)-Adiol might have a role in modulating estrogen-sensitive neuroplastic events in the brain, in the absence of adequate local synthesis of estrone and estradiol.

  1. Elevation of the cortisol-dehydroepiandrosterone ratio in drug-free depressed patients.

    Science.gov (United States)

    Young, Allan H; Gallagher, Peter; Porter, Richard J

    2002-07-01

    Elevated basal cortisol levels are a feature of depressive illness and cause deficits in learning and memory. The adrenal steroid dehydroepiandrosterone (DHEA) has antiglucocorticoid properties that may offer protection against the deleterious effects of cortisol. The authors examined the ratio of cortisol to DHEA in drug-free depressed patients and a matched comparison group. Cortisol and DHEA were measured in saliva samples from 39 patients with unipolar depression who had been medication free for at least 6 weeks and 41 healthy comparison subjects. The molar cortisol-DHEA ratio was significantly higher in the depressed patients than in the healthy comparison subjects. Cortisol-DHEA ratios from saliva samples taken at 8:00 p.m. correlated positively with length of current depressive episode. Elevated cortisol-DHEA ratios may be a state marker of depressive illness and may contribute to the associated deficits in learning and memory. Administration of DHEA or other antiglucocorticoid treatments may reduce neurocognitive deficits in major depression.

  2. Na+ K(+)-ATPase activity in response to exogenous dehydroepiandrosterone administration in aging rat brain.

    Science.gov (United States)

    Taha, Asia; Mishra, Monika; Baquer, N Z; Sharma, Deepak

    2008-12-01

    Influence of exogenously administered dehydroepiandrosterone (DHEA) on the activity of Na+ K+ ATPase was investigated in synaptosomal fraction from cerebral cortex, cerebellum, hippocampus and medulla regions of brain of 12 and 22 months old rats. DHEA was administered daily at the dose of 30 mg/kg/body wt, intraperitonially (ip) in both the age groups of rats for 1 month. Results showed that Na+ K+ ATPase activity, increased in DHEA treated rats in both the age groups. In terms of per cent increase, 22 months old animals showed significant increase in Na+ K+ ATPase activity in the synaptosomal fraction of all the four brain regions than in 12 months old DHEA-treated rats. This showed that exogenous DHEA modulated the activity of Na+ K+ ATPase and also protected the age-related loss of membrane integrity and functions. It was concluded that exogenous DHEA might be beneficial in terms of neuroprotection against age-related loss of Na+ K+ ATPase mediated brain functions like learning and memory.

  3. DEHYDROEPIANDROSTERONE AND ORAL GLUCOSE TOLERANCE TEST IN YOUNG WOMEN: IS IT RELATED TO EACH OTHER?

    Directory of Open Access Journals (Sweden)

    A.M AMINI

    2001-09-01

    Full Text Available Introduction. In this study we wanted to compare the means of area under the curve (AVC of glucose tolerance test in young women depending on dehydroepiandrosteron (DHEA levels. Methods. Selected subjects were examined for DHEA and glucose tolerance test. At first, they were divided into two groups (under the mean of DHEA vs above the mean of DHEA and then into three groups (under the mean-SD, between the mean±SD, above the mean + SD. 37 young women with no abnormality whose 8MI was below 30 Kg/m2 they were refered to research center of endocrinology and metabolism of IUMSHS. Results. The mean of DHEA was 2895±1113 ng/ml. The mean of AUC was 745±104.7 mmol/l/min in women under the mean of DHEA and 670±51.9 mmol/l/min in women above the mean of DHEA (P < 0.05. In comparison of women based on mean±SD, the AVe was 786±88.3, 691. 7 ± 77.5 and 670.8±92.5 mmol/l/min, respectively. Results showed a significant decrease of AVC in women above the mean+ SO of DHEA (P < 0.05. Discussion. This study suggests that in young healthy women DHEA can increase the glucose tolerance.

  4. Determination of Cortisol and Dehydroepiandrosterone Levels in Saliva for Screening of Periodontitis in Older Japanese Adults

    Directory of Open Access Journals (Sweden)

    Toshihiro Ansai

    2009-01-01

    Full Text Available Background. Recent reports have found a positive relationship between periodontitis and the hormones cortisol and dehydroepiandrosterone (DHEA. We investigated the associations between those levels and periodontitis in never-smokers and smokers of elderly subjects. Subjects and Methods. Cortisol and DHEA levels in saliva were determined in 171 subjects (85 males, 86 females, with clinical examinations including probing depth (PD and clinical attachment loss (CAL also performed. Results. Smoking had effects on cortisol and DHEA levels, and those were significantly associated with severe PD and CAL in never-smokers. According to ROC analysis, the cutoff values of cortisol and DHEA to obtain the optimal sensitivity and specificity for detecting severe periodontitis were 2.06 ng/mL and 60.24 pg/mL, respectively, for PD, and 2.12 ng/mL and 61.78 pg/mL, respectively, for CAL. Conclusions. Assessment of hormone levels may be a useful screening method for periodontitis, though limited to never-smokers.

  5. Dehydroepiandrosterone Inhibited the Bone Resorption through the Upregulation of OPG/RANKL

    Institute of Scientific and Technical Information of China (English)

    Yudong Wang; Ling Wang; Dajin Li; Wenjun Wang

    2006-01-01

    The plasma level of dehydroepiandrosterone (DHEA) is decreases gradually along with aging. The beneficial effects of DHEA as an anti-aging steroid, such as the stimulatory effect on immune system, anti-diabetes mellitus,anti-atherosclerosis, anti-dementia, anti-obesity and anti-osteoporosis have been demonstrated in experiment both in vitro and in vivo. It is important to investigate the effective mechanism of DHEA in therapeutics for postmenopausal osteoporosis. Having isolated and cultured osteoblasts (Obs) and osteoclasts (Ocs), we analysed the effect of DHEA on osteoblastic viability, regulation of DHEA on the expression of osteoprotegerin(OPG)/receptor activator of NF-κB ligand (RANKL) mRNA in Obs, and then observed the action of DHEA on bone resorption of Ocs in the presence or absence of Obs. The results showed that DHEA improved viability of Obs within the concentration range of 10-8-10-6 M, especially at the concentration of 10-7 M. DHEA could apparently increase the ratio of OPG/RANKL mRNA in Obs. In the presence of Obs, DHEA could decrease the number and area of absorption lacuna of specula. We concluded, therefore, only in the presence of Obs, DHEA could inhibit the bone resorption of Ocs, which may be mediated by OPG/RANKL of Obs.

  6. Evaluation of testosterone metabolites/dehydroepiandrosterone as the indicators of testosterone administration in horse doping

    Energy Technology Data Exchange (ETDEWEB)

    Kim, J.Y.; Kim, S.J. [Korea Racing Association, Kyonggi (Korea); Kyong, J.B. [Hanyang University, Seoul (Korea); Choi, M.H.; Chung, B.C. [Korea Institute of Science and Technology, Seoul (Korea)

    1999-06-01

    The metabolism of testosterone (17{beta}-hydroxy-androst-4-en-3-one) was confirmed in horse after a single intramuscular administration of testosterone cypionate (750 mg). Solvent extracts of urine obtained with enzymatic hydrolysis and methanolysis were analyzed by GC/MS after oxime t-butyldimethylsilyl (oxime-TBDMS) derivatization. the structures of four urinary metabolite after testosterone administration in horse were determined based on EI mass spectra and 5{alpha}-androstane-3{beta}, 17{alpha}-diol and 5a-androstane-3{beta}-ol--17one as major was confirmed with authentic standard. Also the concentrations of 5{alpha}--androstane-3{beta}, 17{alpha}-diol, 5{alpha}-androstane-3{beta}, 17{beta}-diol, dehydroepiandrosterone (DHEA), 5{alpha}-androstane-3{beta}-ol-17-one and testosterone were determined in the urine of normal subjects and the urine after administration. The recovery and detection limit in the most drugs were 86.3{approx}94.7% and 1{approx}3 ppb, respectively. Correlation coefficients for calibration were in the range of 0.984{approx}0.999. Excretion profile of testosterone presents the rapid and large increasement up to maximum values as days 5 after administration and the slow regression. The relative ratios of testosterone, its metabolites over DHEA were determined for indication of testosterone administration in horse doping. 13 refs., 5 figs., 1 tab.

  7. Dehydroepiandrosterone decreases while cortisol increases in vitro growth and viability of Entamoeba histolytica.

    Science.gov (United States)

    Carrero, Julio C; Cervantes, Claudia; Moreno-Mendoza, Norma; Saavedra, Emma; Morales-Montor, Jorge; Laclette, Juan P

    2006-02-01

    In vitro exposure of Entamoeba histolytica trophozoites to the sex steroids 17beta-estradiol, progesterone, and dehydrotestosterone had little effect on parasite viability or proliferation. However, treatment with the adrenal steroid dehydroepiandrosterone (DHEA) markedly inhibited parasite proliferation, adherence and motility, and at a certain dose it induced trophozoite lysis. The opposite effect on proliferation was found when the trophozoites were exposed to cortisol. Moreover, DHEA decreased while cortisol increased the parasite's DNA synthesis determined by 3H-thymidine incorporation. Trophozoite lysis by DHEA appeared to be caused by a necrotic rather than an apoptotic process, as observed in propidium iodide and terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling assays. A possible mechanisms of action was derived from experiments demonstrating that the activity of a putative 3-hydroxy-3-methyl glutaryl CoA reductase detected in trophozoite extracts was inhibited in the presence of DHEA. Contrary to its in vitro inhibitory effect, in vivo administration of DHEA to infected hamsters resulted in exacerbation of the amebic liver abscesses. These results demonstrated that androgen steroids act directly upon E. histolytica growth and viability, and may shed new light on some age and gender differences in disease progression, as well as finding application in the drug treatment of human amebiasis.

  8. Influence of the dissolution medium on the release of dehydroepiandrosterone from lipophilic suppositories

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    Kasperek1 Regina

    2014-06-01

    Full Text Available Suppositories with cocoa butter containing dehydroepiandrosterone (DHEA without and with the addition of Span 80 and Tween 80 as surfactants with low and high HLB values were prepared. The physical properties and the drug content of all prepared suppositories were in accordance with the pharmacopoeial requirements. The release study tests in three dissolution media such as water, lactic acid solution at pH 4.2 and phosphate buffer at pH 7.4 were carried out. In acidic and alkalic media only about 10% and 27% of DHEA were released, respectively. The addition of Span 80 to the suppository mass did not improve the release process, but the addition of Tween 80 caused the increase in the amount of DHEA released in the acidic medium to about 35%. The data showed that rectal administration of suppositories with DHEA based on cocoa butter caused about 30% availability and after vaginal administration, only topical activity can be expected. By the addition of Tween 80 to the suppository mass availability of DHEA of about 35% from vaginal suppositories can be achieved.

  9. Sulfate transport in toad skin

    DEFF Research Database (Denmark)

    Larsen, Erik Hviid; Simonsen, K

    1988-01-01

    1. In short-circuited toad skin preparations exposed bilaterally to NaCl-Ringer's containing 1 mM SO2(-4), influx of sulfate was larger than efflux showing that the skin is capable of transporting sulfate actively in an inward direction. 2. This active transport was not abolished by substituting ...

  10. Interaction of PACls with sulfate

    Institute of Scientific and Technical Information of China (English)

    XU Yi; WANG Dong-Sheng; TANG Hong-Xiao

    2004-01-01

    This article discusses the influential factors on Al13 separation considering the interaction of sulfate with various polyaluminum chloride(PACl). The experimental results showed that the basicity(B=[OH]/[Al]), the concentration of PACl and Al/SO4 ratio exhibited significant roles in the PACl-sulfate reaction. It indicated that different species in various PACl underwent different reaction pathway with sulfate. The Alc, colloidal species, formed precipitation quickly with sulfate, while Alb, oligomers and polymers, undergoes slow crystallization. And Ala, monomers, reacts with sulfate to form soluble complexes. The kinetic difference of reaction made it possible to realize the separation of Alb and further purification. The decrease of Ala resulted in the limit of ferron method was also mentioned.

  11. Fine-needle aspiration cytology of ovarian steroid cell tumor: A rare case report

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    Nidhi Agrawal

    2015-01-01

    Full Text Available Steroid cell tumors (SCTs of the ovary are a rare subgroup of sex cord tumors that account for less than 0.1% of all ovarian tumors. These tumors can produce steroids, especially testosterone, which produces symptoms such as hirsutism, amenorrhea/oligomenorrhea, and male patterned voice. For evaluation of the androgen excess, testosterone and dehydroepiandrosterone sulfate (DHEA-S are the first laboratory tests to be measured. Abdominal ultrasound and magnetic resonance imaging (MRI are useful radiologic imaging techniques. Although SCTs are generally benign, the risk of malignant transformation is always present. Surgical excision of tumor is the most important and hallmark treatment. The present case signifies the early preoperative diagnosis of a virilizing SCT, based on cytological features and its careful correlation with clinicopathological and radiological findings.

  12. Steroid Cell Tumor of the Ovary in an Adolescent: A Rare Case Report

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    Gokhan Boyraz

    2013-01-01

    Full Text Available Steroid cell tumors (SCTs of the ovary are a rare subgroup of sex cord tumors, account for less than 0.1% of all ovarian tumors, and also will present at any age. These tumors can produce steroids, especially testosterone, and may give symptoms like hirsutism, hair loss, amenorrhea, or oligomenorrhea. For the evaluation of androgen excess, testosterone and dehydroepiandrosterone sulfate (DHEA-S are the first laboratory tests to be measured. A pelvic ultrasound and a magnetic resonance imaging are useful radiologic imaging techniques. Although steroid cell tumors are generally benign, there is a risk of malignant transformation and clinical malignant formation. Surgery is the most important and hallmark treatment.

  13. Role of androgen and estrogen receptors for the action of dehydroepiandrosterone (DHEA).

    Science.gov (United States)

    Engdahl, Cecilia; Lagerquist, Marie K; Stubelius, Alexandra; Andersson, Annica; Studer, Erik; Ohlsson, Claes; Westberg, Lars; Carlsten, Hans; Forsblad-d'Elia, Helena

    2014-03-01

    Dehydroepiandrosterone (DHEA) is an abundant steroid hormone, and its mechanism of action is yet to be determined. The aim of this study was to elucidate the importance of androgen receptors (ARs) and estrogen receptors (ERs) for DHEA function. Orchidectomized C57BL/6 mice were treated with DHEA, DHT, 17β-estradiol-3-benzoate (E2), or vehicle. Orchidectomized AR-deficient (ARKO) mice and wild-type (WT) littermates were treated with DHEA or vehicle for 2.5 weeks. At termination, bone mineral density (BMD) was evaluated, thymus and seminal vesicles were weighted, and submandibular glands (SMGs) were histologically examined. To evaluate the in vivo ER activation of the classical estrogen signaling pathway, estrogen response element reporter mice were treated with DHEA, DHT, E2, or vehicle, and a reporter gene was investigated in different sex steroid-sensitive organs after 24 hours. DHEA treatment increased trabecular BMD and thymic atrophy in both WT and ARKO mice. In WT mice, DHEA induced enlargement of glands in the SMGs, whereas this effect was absent in ARKO mice. Furthermore, DHEA was able to induce activation of classical estrogen signaling in bone, thymus, and seminal vesicles but not in the SMGs. In summary, the DHEA effects on trabecular BMD and thymus do not require signaling via AR and DHEA can activate the classical estrogen signaling in these organs. In contrast, DHEA induction of gland size in the SMGs is dependent on AR and does not involve classical estrogen signaling. Thus, both ERs and ARs are involved in mediating the effects of DHEA in an organ-dependent manner.

  14. Nongenomic bronchodilating action elicited by dehydroepiandrosterone (DHEA) in a guinea pig asthma model.

    Science.gov (United States)

    Espinoza, Julia; Montaño, Luis M; Perusquía, Mercedes

    2013-11-01

    Primates secrete large amounts of the precursor steroid dehydroepiandrosterone (DHEA); in humans, its levels are low during childhood and start declining after the fourth decade. It has been postulated that the progressive decline in DHEA levels may be related with the severity of asthma associated with age. To determine whether DHEA may regulate the airway smooth muscle (ASM) activity, isolated tracheal rings with and without epithelium from male guinea pigs were isometrically recorded to characterize the response of ASM to DHEA at different concentrations on KCl- and carbachol (CCh)-induced contraction as well as on ovalbumin (OVA)-induced contraction in sensitized guinea pigs. Additionally, we used barometric plethysmography in sensitized guinea pigs in order to compare changes of the lung resistance increased by the antigen challenge to OVA in the absence and presence of different doses of DHEA. DHEA concentration-dependently abolished the contraction to KCl, CCh and OVA, and no differences were found in preparations with and without epithelium. DHEA-induced relaxation was not modified by the suppression of protein synthesis or transcription, pharmacological inhibition of nitric oxide (NO) synthase, nor by antagonist of β2-adrenergic receptors or an inhibitor of the 3β-HSD enzyme. Likewise, Ca(2+)-induced contraction in Ca(2+)-free depolarized tissues was antagonized by DHEA, and the contraction to the L-type voltage-dependent calcium channel activator (Bay K 8644) was inhibited by DHEA. Furthermore, DHEA prevented OVA-induced increases in lung resistance. These results indicate that DHEA-induced relaxation in ASM is a nongenomic (membrane) action and is not produced after its bioconversion. The data suggest that DHEA-induced relaxation is an epithelium- and NO-independent mechanism that involves a blockade of voltage-dependent calcium channels and possible non-selective cation channels. Copyright © 2013 Elsevier Ltd. All rights reserved.

  15. Oxidative stress-mediated brain dehydroepiandrosterone (DHEA formation in Alzheimer’s disease diagnosis

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    Geogres eRammouz

    2011-11-01

    Full Text Available Neurosteroids are steroids made by brain cells independently of peripheral steroidogenic sources. The biosynthesis of most neurosteroids is mediated by proteins and enzymes similar to those identified in the steroidogenic pathway of adrenal and gonadal cells. Dehydroepiandrosterone (DHEA is a major neurosteroid identified in the brain. Over the years we have reported that, unlike other neurosteroids, DHEA biosynthesis in rat, bovine, and human brain is mediated by an oxidative stress-mediated mechanism, independent of the cytochrome P450 17a-hydroxylase/17,20-lyase (CYP17A1 enzyme activity found in the periphery. This alternative pathway is induced by pro-oxidant agents, such as Fe2+ and b-amyloid peptide. Neurosteroids are involved in many aspects of brain function, and as such, are involved in various neuropathologies, including Alzheimer’s disease (AD. AD is a progressive, yet irreversible neurodegenerative disease for which there are limited means for ante-mortem diagnosis. Using brain tissue specimens from control and AD patients, we provided evidence that DHEA is formed in the AD brain by the oxidative stress-mediated metabolism of an unidentified precursor, thus depleting levels of the precursor in the blood stream. We tested for the presence of this DHEA precursor in human serum using a Fe2+-based reaction and determined the amounts of DHEA formed. Fe2+ treatment of the serum resulted in a dramatic increase in DHEA levels in control patients, whereas only a moderate or no increase was observed in AD patients. The DHEA variation after oxidation correlated with the patients’ cognitive and mental status. In this review, we present the cumulative evidence for oxidative stress as a natural regulator of DHEA formation and the use of this concept to develop a blood-based diagnostic tool for neurodegenerative diseases linked to oxidative stress, such as AD.

  16. Lack of effect of intravaginal dehydroepiandrosterone (DHEA, prasterone) on the endometrium in postmenopausal women.

    Science.gov (United States)

    Portman, David J; Labrie, Fernand; Archer, David F; Bouchard, Céline; Cusan, Leonello; Girard, Ginette; Ayotte, Normand; Koltun, William; Blouin, François; Young, Douglas; Wade, Anthony; Martel, Céline; Dubé, Robert

    2015-12-01

    This study aims to evaluate the effects of intravaginal dehydroepiandrosterone (DHEA, prasterone) on the endometrium in postmenopausal women. Intravaginal DHEA (6.5 mg) was administered daily for 52 weeks to 422 women who had endometrial biopsy at baseline and end of study, whereas 15 women were similarly treated for 26 to 52 weeks. Participants in three other studies received 3.25 mg (n = 126), 6.5 mg (n = 129), or 13 mg (n = 30) of DHEA for 12 weeks; women similarly had baseline and end-of-study biopsies. Endometrial biopsy samples were available for 668 women at baseline and end of study, with sufficient material for analysis. Endometrial atrophy or inactive endometrium (668 women) was found in all women treated with intravaginal DHEA. Similar atrophy was observed in 119 of 121 participants with sufficient material for analysis who received placebo. After cessation of estradiol secretion by the ovaries at menopause, the estrogens made by mechanisms of intracrinology are inactivated intracellularly at their site of formation and action, thus maintaining serum estradiol at biologically inactive concentrations to avoid stimulation of the endometrium. The absence of enzymes that are able to transform DHEA into estrogens in the endometrium explains the typical endometrial atrophy in all normal postmenopausal women in the presence of variable concentrations of circulating endogenous DHEA. According to these mechanisms, the inactive sex steroid precursor DHEA administered intravaginally acts exclusively in the vagina, whereas all serum sex steroids remain well within the biologically inactive postmenopausal reference range, thus avoiding any stimulation of the already atrophic endometrium.

  17. Biotransformation of dehydroepiandrosterone (DHEA) with Penicillium griseopurpureum Smith and Penicillium glabrum (Wehmer) Westling.

    Science.gov (United States)

    Huang, Li-Hua; Li, Juan; Xu, Gong; Zhang, Xiang-Hua; Wang, Yang-Guang; Yin, Ye-Lin; Liu, Hong-Min

    2010-12-12

    Microbial transformation of dehydroepiandrosterone (DHEA, 1) using Penicillium griseopurpureum Smith and Penicillium glabrum (Wehmer) Westling has been investigated. Neither fungi had been examined previously for steroid biotransformation. One novel metabolic product of DHEA (1) transformed with P. griseopurpureum Smith, 15α-hydroxy-17a-oxa-d-homo-androst-4-ene-3,17-dione (5), was reported for the first time. The steroid products were assigned by interpretation of their spectral data such as (1)H NMR, (13)C NMR, IR, and HR-MS spectroscopy. P. griseopurpureum Smith was proven to be remarkably efficient in oxidation of the DHEA (1) into androst-4-en-3,17-dione (2). The strain was also observed to yield different monooxygenases to introduce hydroxyl groups at C-7α, -14α, and -15α positions of steroids. Preference for Baeyer-Villiger oxidation to lactonize D ring and oxidation of the 3β-alcohol to the 3-ketone were observed in both incubations. The strain of P. glabrum (Wehmer) Westling catalyzed the steroid 1 to generate both testololactone 3, and d-lactone product with 3β-hydroxy-5-en moiety 8. In addition, the strain promoted hydrogenation of the C-5 and C-6 positions, leading to the formation of 3β-hydroxy-17a-oxa-d-homo-5α-androstan-3,17-dione (9). The biotransformation pathways of DHEA (1) with P. glabrum (Wehmer) Westling and P. griseopurpureum Smith have been investigated, respectively. Possible metabolic pathways of DHEA (1) were proposed. Copyright © 2010. Published by Elsevier Inc.

  18. Androgenic action of dehydroepiandrosterone (DHEA) on nerve density in the ovariectomized rat vagina.

    Science.gov (United States)

    Pelletier, Georges; Ouellet, Johanne; Martel, Céline; Labrie, Fernand

    2013-08-01

    We have recently reported that dehydroepiandrosterone (DHEA) increases the density of nerve fibers in the ovariectomized (OVX) rat vagina. To better define the mechanism of action of DHEA, we have examined the effect of DHEA, conjugated estrogens (premarin) and the potent blocker of estrogen action acolbifene on the innervation in the lamina propria in the OVX rat vagina. Female Sprague-Dawley rats (10-12 weeks old) were used. Innervation of the vagina was examined 9 months after OVX and was compared to that of OVX animals treated daily with DHEA (80 mg/kg) by topical application on the skin, premarin (0.5 mg/kg) orally as well as acolbifene (2.5 mg/kg) orally administrated alone or in combination with DHEA or premarin. Four histological sections from each vagina (5 animals/group) were immunostained using antibodies to the panneuronal marker protein gene product 9.5 (PGP 9.5). The areas were measured by stereological analysis. OVX reduced the area of the lamina propria to 44% of the intact value, an effect which was reversed to 69% and 84% of the intact value by DHEA and premarin, respectively, at the doses used. When acolbifene was used, no inhibition of the stimulatory effect of DHEA was observed, while the action of premarin was completely blocked. Evaluation of the PGP 9.5 fiber density revealed that DHEA treatment increased the density of fibers by 60% compared to OVX animals, while a further 27% increase was observed when acolbifene was combined with DHEA. Premarin, on the other hand, had no effect on the density of PGP 9.5 fibers. Considering that the antiestrogen acolbifene had no inhibitory effect on the effect of DHEA in rat vagina while blocking the stimulatory effect of premarin, the present data indicate that DHEA exerts its stimulatory effect on the fiber density through an androgenic action. © 2013 International Society for Sexual Medicine.

  19. Serum dehydroepiandrosterone levels are associated with lower risk of type 2 diabetes: the Rotterdam Study.

    Science.gov (United States)

    Brahimaj, Adela; Muka, Taulant; Kavousi, Maryam; Laven, Joop S E; Dehghan, Abbas; Franco, Oscar H

    2017-01-01

    Previous literature documents controversial results for the impact of dehydroepiandrosterone (DHEA) in glucose metabolism. We aimed to assess the associations between serum levels of DHEA and its main derivatives DHEA sulphate (DHEAS) and androstenedione, as well as the ratio of DHEAS to DHEA, and risk of type 2 diabetes. We used data on serum levels of DHEA, DHEAS and androstenedione from 5189 middle-aged and elderly men and women from the prospective population-based Rotterdam Study. Type 2 diabetes was defined as a fasting blood glucose ≥7.0 mmol/l or a non-fasting blood glucose ≥11.1 mmol/l. During a median follow-up of 10.9 years, 643 patients with incident type 2 diabetes were identified. After adjusting for age, sex, cohort, fasting status, fasting glucose and insulin, and BMI, both serum DHEA levels (per 1 unit natural log-transformed, HR 0.76, 95% CI 0.67, 0.87) and serum DHEAS levels (per 1 unit natural log-transformed, HR 0.82, 95% CI 0.73, 0.92) were inversely associated with risk of type 2 diabetes in the total population. Further adjustment for alcohol, smoking, physical activity, prevalent cardiovascular disease, serum total cholesterol, use of lipid-lowering medications, systolic BP, treatment for hypertension, C-reactive protein, oestradiol and testosterone did not substantially affect the association between DHEA and incident type 2 diabetes (per 1 unit natural log-transformed, HR 0.80, 95% CI 0.65, 0.99), but abolished the association between DHEAS and type 2 diabetes. Androstenedione was not associated with risk of type 2 diabetes, nor was DHEAS to DHEA ratio. DHEA serum levels might be an independent marker of type 2 diabetes.

  20. Effect of dehydroepiandrosterone administration in patients with poor ovarian response according to the Bologna criteria.

    Directory of Open Access Journals (Sweden)

    Bei Xu

    Full Text Available BACKGROUND: Dehydroepiandrosterone (DHEA is now widely used as an adjuvant to IVF treatment protocols in poor responders. However, clinical evidence for DHEA on improvement of ovarian response and IVF outcome is still limited, the validity of the results of the earlier studies, especially the varied inclusion criteria, is a subject of debate. Recently, the ESHRE Working Group developed a new definition, the Bologna criteria. The aim of the current study was to investigate the potential effect of DHEA treatment on in vitro fertilization (IVF outcome of poor ovarian responders that fulfill the Bologna criteria. METHODS: This study investigated 386 poor ovarian responders that fulfill the Bologna criteria. Patients underwent IVF-ET treatment with the GnRH antagonist protocol. The study group contained 189 patients, who received 75 mg of DHEA daily (25 mg three times daily before the IVF cycle. The control group was composed of 197 patients who received infertility treatment, but did not receive DHEA. The IVF outcome parameters in each group were compared. RESULTS: The study and control groups did not show statistically significant differences in terms of patient demographics characteristics, mean numbers of oocytes retrieved, mature oocytes, fertilization rate, cleavage rate, or embryo availability. While the DHEA group demonstrated significantly higher implantation rates (18.7% vs. 10.1%; P<0.01 and ongoing PRs (26.7% vs. 15.8%; P<0.05 as compared with the control. CONCLUSIONS: DHEA pre-treatment does not significantly increase oocyte yield. However, the ongoing PRs in this subgroup of women are significantly higher after DHEA administration, suggesting that DHEA may increase IVF results by improving oocyte and embryo quality.

  1. Effects of ovariectomy and dehydroepiandrosterone (DHEA) on vaginal wall thickness and innervation.

    Science.gov (United States)

    Pelletier, Georges; Ouellet, Johanne; Martel, Céline; Labrie, Fernand

    2012-10-01

    One mechanism by which low sexual steroid activity observed after menopause could cause sexual dysfunction is by deficient vaginal innervation. Recently, it has been shown that intravaginal administration of dehydroepiandrosterone (DHEA) could produce beneficial effects on sexual dysfunction in postmenopausal women. The goal of this study was to determine if DHEA could modify innervation in the rat vagina. The area occupied by the nerve fibers immunoreactive for protein gene product 9.5 (PGP 9.5), a panneuronal marker or tyrosine hydroxylase (TH), a sympathetic nerve fiber marker, in the lamina propria and muscular layers, respectively, as well as the total area of each of these 2 layers were measured by stereological analysis. The innervation of the rat vagina was examined 9 months after ovariectomy (OVX) compared to intact animals and treatment of OVX animals with DHEA (80 mg/kg). Four sections from each vagina (5 animals/groups) were immunostained. In OVX animals, the lamina propria area was decreased to 44%, an effect which was reversed by DHEA to 69% of the intact value. OVX also caused a 59% decrease in the area of PGP 9.5 fibers, an effect which was prevented by DHEA, thus showing a 68% stimulatory effect of DHEA on the density of PGP 9.5 fibers in the lamina propria compared to OVX animals. Following OVX, the muscular layer area was decreased by 61%. DHEA treatment induced 118% and 71% increases in TH fiber area compared to OVX and intact animals, respectively. The density of TH fibers was 182% increased over intact controls by DHEA treatment of OVX animals. The relatively potent stimulatory effect of DHEA on intravaginal nerve fiber density provides a possible explanation for the beneficial effects of intravaginal DHEA on sexual dysfunction observed in postmenopausal women. © 2012 International Society for Sexual Medicine.

  2. Inhibition of methylation of DNA by dimethylnitrosamine (DMN) in dehydroepiandrosterone-fed rats

    Energy Technology Data Exchange (ETDEWEB)

    Prasanna, H.R.; Magee, P.N. (Temple University School of Medicine, Philadelphia, PA (USA)); Harrington, G.W. (Temple Univ., Philadelphia, PA (USA)); Hart, R.W. (National Center for Toxicological Research, Jefferson, AR (USA))

    1989-01-01

    The influence of the anticarcinogen dehydroepiandrosterone (DHEA) on the metabolism and macromolecular interactions of the potent hepatocarcinogen dimethylnitrosamine (NDMA) was investigated. Male Sprague-Dawley rats (2-3 mo old) were fed DHEA for 14 d at a dietary level 0.8%. Compared with pair-fed controls, the liver weights of the DHEA-treated animals increased significantly (11.7 vs. 7.1 g) with increase, per total liver, in proteins including those of cytosol and microsomes as well as cytochromes P-450 and b{sub 5}. DNA content of the liver, however, remained constant. Five hours after a single ip dose of ({sup 14}C)NDMA (30 mg/kg body wt, 42 {mu}Ci/rat) DNA methylation was reduced in the DHEA-fed animals as measured by 7-methyl- and O{sup 6}-methylguanine per mole of guanine, by 39 and 31%, respectively. The rate of NDMA metabolism was slightly higher in the DHEA-fed rats as determine in vivo by the exhalation of {sup 14}CO{sub 2} and by the declining concentrations of NDMA in the blood. The incorporation of radioactivity from ({sup 14}C)NDMA into hepatic proteins in vivo was greater (2.1-fold) in the DHEA-fed rats. Our results suggest that feeding rats with the adrenal steroid DHEA enhances the metabolic activation of NDMA in vivo, and that the increased association of NDMA-derived metabolites with increased hepatic cellular proteins may be partially responsible for protection of hepatic DNA from NDMA-induced damage.

  3. The effect of dehydroepiandrosterone (DHEA) on renal function and metabolism in diabetic rats.

    Science.gov (United States)

    Jahn, Matheus Parmegiani; Gomes, Luana Ferreira; Jacob, Maria Helena Vianna Metello; da Rocha Janner, Daiane; Araújo, Alex Sander da Rosa; Belló-Klein, Adriane; Ribeiro, Maria Flávia Marques; Kucharski, Luiz Carlos

    2011-05-01

    Dehydroepiandrosterone (DHEA) is an endogenous steroid hormone involved in a number of biological actions in humans and rodents, but its effects on renal tissue have not yet been fully understood. The aim of this study is to assess the effect of DHEA treatment on diabetic rats, mainly in relation to renal function and metabolism. Diabetic rats were treated with subcutaneous injections of a 10mg/kg dose of DHEA diluted in oil. Plasma glucose and creatinine, in addition to urine creatinine, were quantified espectophotometrically. Glucose uptake and oxidation were quantified using radioactive glucose, the urinary Transforming Growth Factor β(1) (TGF-β(1)) was assessed by enzyme immunoassay, and the total glutathione in the renal tissue was also measured. The diabetic rats displayed higher levels of glycemia, and DHEA treatment reduced hyperglycemia. Plasmatic creatinine levels were higher in the diabetic rats treated with DHEA, while creatinine clearance was lower. Glucose uptake and oxidation were lower in the renal medulla of the diabetic rats treated with DHEA, and urinary TGF-β(1), as well as total gluthatione levels, were higher in the diabetic rats treated with DHEA. DHEA treatment was not beneficial to renal tissue, since it reduced the glomerular filtration rate and renal medulla metabolism, while increasing the urinary excretion of TGF-β(1) and the compensatory response by the glutathione system, probably due to a mechanism involving a pro-oxidant action or a pro-fibrotic effect of this androgen or its derivatives. In conclusion, this study reports that DHEA treatment may be harmful to renal tissue, but the mechanisms of this action have not yet been fully understood. Copyright © 2011 Elsevier Inc. All rights reserved.

  4. Effects of dehydroepiandrosterone (DHEA) on follicular dynamics in a diminished ovarian reserve in vivo model.

    Science.gov (United States)

    Hassa, Hikmet; Aydin, Yunus; Ozatik, Orhan; Erol, Kevser; Ozatik, Yasemin

    2015-06-01

    The objective of this study was to determine whether there are changes in primary, primordial, and growing follicles after dehydroepiandrosterone (DHEA) administration in rats that have diminished ovarian reserve (DOR) due to 4-vinylcyclohexene diepoxide (VCD) application, and to examine the mechanism of the probable effect of DHEA on folliculogenesis. Two groups of Wistar rats were used. In Group A unilateral oophorectomy (eight rats) was carried out on day-0. The remaining study ovary was removed by relaparotomy after VCD (160 mg/kg, intraperitoneally) was administered for 15 days. In Group B unilateral oophorectomy (eight rats) was carried out on day-0. The remaining study ovary was removed by relaparotomy after VCD (160 mg/kg, intraperitoneally) administration for 15 days followed by DHEA (60 mg/kg body weight) daily for 45 days. Primordial, primary, and growing (secondary+antral) follicles were counted in 1,664 sections from 32 ovaries. In all three types of follicles (primordial, primary, and growing), the number of follicles significantly decreased in the study ovaries compared to the control ovaries in both Group A and Group B. In Group B, atresia rates were significantly lower in the study ovary compared to the control ovary in all of the follicular groups: primordial (p=0.02), primary (p=0.01), and growing (p=.027). To demonstrate the probable effects of DHEA on follicular dynamics, we also compared the study ovaries in both groups; the primordial (p=0.027), primary (p=0.031), and growing (p=0.04) number of follicles were significantly higher in Group B compared to Group A. In conclusion, our findings suggest that DHEA administration in DOR rats due to VCD results in a larger follicular pool. Decreased atresia may be one of the possible effects of DHEA in DOR cases. Whatever the mechanism, DHEA treatment potentially may be useful clinically as a means to increase the number of gonadotropin-responsive follicles for ovarian stimulation.

  5. Bovine liver slices: A multifunctional in vitro model to study the prohormone dehydroepiandrosterone (DHEA).

    Science.gov (United States)

    Rijk, Jeroen C W; Bovee, Toine F H; Peijnenburg, Ad A C M; Groot, Maria J; Rietjens, Ivonne M C M; Nielen, Michel W F

    2012-09-01

    Biotransformation of inactive prohormones like dehydroepiandrosterone (DHEA) can lead to the formation of potent androgens and subsequent androgenic responses in target tissues. In the present study, precision-cut bovine liver slices were used to study the effects of DHEA on the metabolite, transcript and androgenic activity level. Bovine liver slices were exposed for 6h to various concentrations of DHEA. Changes in androgenic activity of the DHEA containing cell culture media were measured using a yeast androgen bioassay and metabolites were identified using ultra performance liquid chromatography time-of-flight mass spectrometry (UPLC-TOFMS), while gene expression in the DHEA-treated liver slices was examined using bovine microarrays and compared with the profile as obtained with 17ß-testosterone (17ß-T). An increase in androgenic activity was observed in the bioassay upon testing of samples from incubations of DHEA with liver slices and the formation of 4-androstenedione (4-AD), 5-androstene-3ß,17ß-diol, 17ß-T, 7α-hydroxy-DHEA, 7-keto-DHEA and 17α-T could be confirmed by UPLC-TOFMS analysis. Exposure of liver slices to DHEA and the strong androgen 17ß-T resulted in the identification of significantly up- and down-regulated genes and revealed similar gene expression profiles for both compounds. The results indicate that DHEA itself is biologically not very active, but is rapidly converted by the liver slices into the more androgen active compounds 4-AD and 17ß-T. Moreover, the present data highlight the multi-functionality of bovine liver slices as an in vitro bioactivation model, allowing the assessment of androgen activity or gene expression as effect-based endpoints for prohormone exposure. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. Neurosteroid dehydroepiandrosterone improves active avoidance retrieval and induces antidepressant-like behavior in rats.

    Science.gov (United States)

    Samardzic, Janko; Hencic, Boris; Jancic, Jasna; Jadzic, Dragana; Djuric, Milos; Obradovic, Dragan I; Svob Strac, Dubravka

    2017-09-08

    Various studies reported beneficial effects of dehydroepiandrosterone (DHEA) and its sulphate (DHEAS), the neurosteroids involved in various brain functions, on synaptic plasticity, neuronal survival, memory, learning and behavior. This study aimed to investigate the behavioral profile of acute DHEA treatment by using active avoidance (AA) task, primarily predictive of the effects on the retrieval-based learning, and by applying forced swim test (FST), for assessment of antidepressant-like potential. Adult male Wistar rats received intraperitoneal injections of either DHEA (2, 10, 20mg/kg) or solvent, 30min prior to testing. DHEA, in a manner resembling an inverted U shape, influenced the retrieval imposed to rats in AA paradigm. The significant improvement of the performance in the retention session was observed following 10mg/kg DHEA treatment and it was not due to the changes in the motor activity, as indicated by unaltered locomotor parameters (inter-trial crossing). Moreover, 10mg/kg of DHEA significantly decreased the duration of immobility in FST, demonstrating antidepressant-like effects. The capability of bicuculline (2mg/kg) to antagonize the effects of DHEA has been evaluated simultaneously. The retrieval-facilitating as well as antidepressant-like effects of 10mg/kg DHEA were counteracted by bicuculline, a competitive antagonist of GABAA receptors, suggesting involvement of GABAergic system. These results support administration of DHEA as potential therapeutic strategy for treating depression and related cognitive impairments, but emphasized the importance of adequate dosing, as DHEA levels that are too high or too low may not be beneficial. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Dehydroepiandrosterone induces human CYP2B6 through the constitutive androstane receptor.

    Science.gov (United States)

    Kohalmy, Krisztina; Tamási, Viola; Kóbori, László; Sárváry, Eniko; Pascussi, Jean-Marc; Porrogi, Pálma; Rozman, Damjana; Prough, Russell A; Meyer, Urs A; Monostory, Katalin

    2007-09-01

    Dehydroepiandrosterone (DHEA), the major precursor of androgens and estrogens, has several beneficial effects on the immune system, on memory function, and in modulating the effects of diabetes, obesity, and chemical carcinogenesis. Treatment of rats with DHEA influences expression of cytochrome P450 (P450) genes, including peroxisome proliferator-activated receptor alpha (PPAR alpha)- and pregnane X receptor (PXR)-mediated induction of CYP4As and CYP3A23, and suppression of CYP2C11. DHEA treatment elevated the expression and activities of CYP3A4, CYP2C9, CYP2C19, and CYP2B6 in primary cultures of human hepatocytes. Induction of CYP3A4 in human hepatocytes was consistent with studies in rats, but induction of CYP2Cs was unexpected. The role of PXR in this response was studied in transient transfection assays. DHEA activated hPXR in a concentration-dependent manner. Because CYP2B6 induction by DHEA in human hepatocytes might involve either PXR or constitutive androstane receptor (CAR) activation, we performed experiments in primary hepatocytes from CAR knockout mice and observed that CAR was required for maximal induction of Cyp2b10 by DHEA. Furthermore, CAR-mediated Cyp2b10 induction by DHEA was inhibited by the inverse agonist of CAR, androstanol (5 alpha-androstan-3 alpha-ol). Further evidence for CAR activation was provided by cytoplasmic/nuclear transfer of CAR upon DHEA treatment. Elucidation of CAR activation and subsequent induction of CYP2B6 by DHEA presented an additional mechanism by which the sterol can modify the expression of P450s. The effect of DHEA on the activation of the xenosensors PPAR alpha, PXR, and CAR, and the consequent potential for adverse drug/toxicant interactions should be considered in humans treated with this nutriceutical agent.

  8. Dehydroepiandrosterone administration improves memory deficits following transient brain ischemia through sigma-1 receptor stimulation.

    Science.gov (United States)

    Yabuki, Yasushi; Shinoda, Yasuharu; Izumi, Hisanao; Ikuno, Tatuya; Shioda, Norifumi; Fukunaga, Kohji

    2015-10-05

    Dehydroepiandrosterone (DHEA) is the most abundant neurosteroid synthesized de novo in the central nervous system. Oral DHEA administration elicits neuroprotection and cognitive improvement, but mechanisms underlying these functions in cerebral ischemia have remained unclear. Since DHEA is the endogenous ligand for the sigma-1 receptor (σ1R), we determined whether oral DHEA administration prevents neuronal cell death and improves cognition via σ1R stimulation in brain ischemia using a 20-min bilateral common carotid artery occlusion (BCCAO) mouse model. Twenty-four hours after BCCAO ischemia, mice were administered DHEA (15 or 30mg/kg p.o.) daily for 11 consecutive days. Memory deficits following brain ischemia were improved by DHEA administration dose-dependently. Accordingly, DHEA administration significantly prevented neuronal cell death in the hippocampal CA1 region in BCCAO mice. Interestingly, DHEA administration rescued decreases in Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) autophosphorylation and phosphorylation of extracellular signal-regulated kinase (ERK) and protein kinase B (Akt) in the CA1 region. Moreover, DHEA administration significantly ameliorated decreases in adenosine 5'-triphosphate (ATP) levels and decreased σ1R expression levels in CA1 following BCCAO ischemia. Finally, co-treatment of mice with the σ1R antagonist NE-100 (1mg/kg, p.o.) blocked DHEA effects on memory improvement and neuroprotection in ischemic mice. Taken together, DHEA prevents neuronal cell death and activates CaMKII via σ1R stimulation, thereby improving cognitive deficits following brain ischemia. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. A novel dehydroepiandrosterone analog improves functional recovery in a rat traumatic brain injury model.

    Science.gov (United States)

    Malik, Amir S; Narayan, Raj K; Wendling, Woodrow W; Cole, Russell W; Pashko, Laura L; Schwartz, Arthur G; Strauss, Kenneth I

    2003-05-01

    The purpose of this study was to investigate the efficacy of a novel steroid, fluasterone (DHEF, a dehydroepiandrosterone (DHEA) analog), at improving functional recovery in a rat model of traumatic brain injury (TBI). The lateral cortical impact model was utilized in two studies of efficacy and therapeutic window. DHEF was given (25 mg/kg, intraperitoneally) at the initial time point and once a day for 2 more days. Study A included four groups: sham injury, vehicle treated (n = 22); injured, vehicle treated (n = 30); injured, pretreated (5-10 min prior to injury, n = 24); and injured, posttreated (initial dose 30 min postinjury, n = 15). Study B (therapeutic window) included five groups: sham injury, vehicle treated (n = 17); injured, vehicle treated (n = 26); and three posttreatment groups: initial dose at 30 min (n = 18), 2 h (n = 23), or 12 h (n = 16) postinjury. Three criteria were used to grade functional recovery. In study A, DHEF improved beam walk performance both with pretreatment (79%) and 30-min posttreatment group (54%; p memory (Morris water maze) and neurological reflexes both revealed significant improvements in all DHEF treatment groups. In cultured rat mesangial cells, DHEF (and DHEA) potently inhibited interleukin-1beta-induced cyclooxygenase-2 (COX2) mRNA and prostaglandin (PGE2) production. In contrast, DHEF treatment did not alter injury-induced COX2 mRNA levels in the cortex or hippocampus. However, DHEF (and DHEA) relaxed ex vivo bovine middle cerebral artery preparations by about 30%, with an IC(50) approximately 40 microM. This was a direct effect on the vascular smooth muscle, independent of the endothelial cell layer. Fluasterone (DHEF) treatments improved functional recovery in a rat TBI model. Possible mechanisms of action for this novel DHEA analog are discussed. These findings suggest an exciting potential use for this agent in the clinical treatment of traumatic brain injury.

  10. Dehydroepiandrosterone indirectly inhibits human osteoclastic resorption via activating osteoblastic viability by the MAPK pathway

    Institute of Scientific and Technical Information of China (English)

    WANG Yu-dong; TAO Min-fang; CHENG Wei-wei; LIU Xiao-hua; WAN Xiao-ping; KeMi Cui

    2012-01-01

    Background Dehydroepiandrosterone (DHEA) is widely known for its beneficial effect on postmenopausal osteoporosis,although the underlying mechanisms remain mainly unclear.In this study,we tried to determine the activation of mitogen-activated protein kinase signal pathways during DHEA treatment and the indirect role of osteoblasts (OBs) on osteoclasts under the DHEA treatment of postmenopausal osteoporosis.@@Methods Primary human OBs and osteoclast-like cells were cultured and,we pretreated OBs with or without U0126 (a highly selective inhibitor of both MEK1 and MEK2).The OBs were treated with DHEA.We then tested the effects of DHEA on human osteoblastic viability,osteoprotegerin production and the expression of phosphor-ERK1/2 (extracellular signal-regulated kinase).In the presence or absence of OBs,the function of osteoclastic resorption upon DHEA treatment was calculated.@@Results DHEA promoted the human osteoblastic proliferation and inhibited the osteoblastic apoptosis within the concentration range of 108-10-6 mol/L (P <0.05,P <0.01,respectively).Within the effective concentration range,the expression of phosphor-ERK1/2 and osteoprotegerin was increased by DHEA and blocked by U0126.In the presence of OBs,DHEA could significantly decrease the number and the area of bone resorption lacuna (P <0.05 and P <0.01,respectively).Without OBs,however,the effects of DHEA on the bone resorption lacuna were almost completely abolished.@@Conclusions DHEA could indirectly inhibit the human osteoclastic resorption through promoting the osteoblastic viability and osteoprotegerin production,which is mediated by mitogen-activated protein kinases signal pathway involving the phosphor-ERK1/2.

  11. Neurosteroid dehydroepiandrosterone interacts with nerve growth factor (NGF receptors, preventing neuronal apoptosis.

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    Iakovos Lazaridis

    2011-04-01

    Full Text Available The neurosteroid dehydroepiandrosterone (DHEA, produced by neurons and glia, affects multiple processes in the brain, including neuronal survival and neurogenesis during development and in aging. We provide evidence that DHEA interacts with pro-survival TrkA and pro-death p75(NTR membrane receptors of neurotrophin nerve growth factor (NGF, acting as a neurotrophic factor: (1 the anti-apoptotic effects of DHEA were reversed by siRNA against TrkA or by a specific TrkA inhibitor; (2 [(3H]-DHEA binding assays showed that it bound to membranes isolated from HEK293 cells transfected with the cDNAs of TrkA and p75(NTR receptors (K(D: 7.4 ± 1.75 nM and 5.6 ± 0.55 nM, respectively; (3 immobilized DHEA pulled down recombinant and naturally expressed TrkA and p75(NTR receptors; (4 DHEA induced TrkA phosphorylation and NGF receptor-mediated signaling; Shc, Akt, and ERK1/2 kinases down-stream to TrkA receptors and TRAF6, RIP2, and RhoGDI interactors of p75(NTR receptors; and (5 DHEA rescued from apoptosis TrkA receptor positive sensory neurons of dorsal root ganglia in NGF null embryos and compensated NGF in rescuing from apoptosis NGF receptor positive sympathetic neurons of embryonic superior cervical ganglia. Phylogenetic findings on the evolution of neurotrophins, their receptors, and CYP17, the enzyme responsible for DHEA biosynthesis, combined with our data support the hypothesis that DHEA served as a phylogenetically ancient neurotrophic factor.

  12. Heparan sulfate and cell division

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    Porcionatto M.A.

    1999-01-01

    Full Text Available Heparan sulfate is a component of vertebrate and invertebrate tissues which appears during the cytodifferentiation stage of embryonic development. Its structure varies according to the tissue and species of origin and is modified during neoplastic transformation. Several lines of experimental evidence suggest that heparan sulfate plays a role in cellular recognition, cellular adhesion and growth control. Heparan sulfate can participate in the process of cell division in two distinct ways, either as a positive or negative modulator of cellular proliferation, or as a response to a mitogenic stimulus.

  13. p-Cresyl Sulfate

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    Tessa Gryp

    2017-01-01

    Full Text Available If chronic kidney disease (CKD is associated with an impairment of kidney function, several uremic solutes are retained. Some of these exert toxic effects, which are called uremic toxins. p-Cresyl sulfate (pCS is a prototype protein-bound uremic toxin to which many biological and biochemical (toxic effects have been attributed. In addition, increased levels of pCS have been associated with worsening outcomes in CKD patients. pCS finds its origin in the intestine where gut bacteria metabolize aromatic amino acids, such as tyrosine and phenylalanine, leading to phenolic end products, of which pCS is one of the components. In this review we summarize the biological effects of pCS and its metabolic origin in the intestine. It appears that, according to in vitro studies, the intestinal bacteria generating phenolic compounds mainly belong to the families Bacteroidaceae, Bifidobacteriaceae, Clostridiaceae, Enterobacteriaceae, Enterococcaceae, Eubacteriaceae, Fusobacteriaceae, Lachnospiraceae, Lactobacillaceae, Porphyromonadaceae, Staphylococcaceae, Ruminococcaceae, and Veillonellaceae. Since pCS remains difficult to remove by dialysis, the gut microbiota could be a future target to decrease pCS levels and its toxicity, even at earlier stages of CKD, aiming at slowing down the progression of the disease and decreasing the cardiovascular burden.

  14. p-Cresyl Sulfate

    Science.gov (United States)

    Gryp, Tessa; Vanholder, Raymond; Vaneechoutte, Mario; Glorieux, Griet

    2017-01-01

    If chronic kidney disease (CKD) is associated with an impairment of kidney function, several uremic solutes are retained. Some of these exert toxic effects, which are called uremic toxins. p-Cresyl sulfate (pCS) is a prototype protein-bound uremic toxin to which many biological and biochemical (toxic) effects have been attributed. In addition, increased levels of pCS have been associated with worsening outcomes in CKD patients. pCS finds its origin in the intestine where gut bacteria metabolize aromatic amino acids, such as tyrosine and phenylalanine, leading to phenolic end products, of which pCS is one of the components. In this review we summarize the biological effects of pCS and its metabolic origin in the intestine. It appears that, according to in vitro studies, the intestinal bacteria generating phenolic compounds mainly belong to the families Bacteroidaceae, Bifidobacteriaceae, Clostridiaceae, Enterobacteriaceae, Enterococcaceae, Eubacteriaceae, Fusobacteriaceae, Lachnospiraceae, Lactobacillaceae, Porphyromonadaceae, Staphylococcaceae, Ruminococcaceae, and Veillonellaceae. Since pCS remains difficult to remove by dialysis, the gut microbiota could be a future target to decrease pCS levels and its toxicity, even at earlier stages of CKD, aiming at slowing down the progression of the disease and decreasing the cardiovascular burden. PMID:28146081

  15. ANDROGEN LEVELS IN PREECLAMPSIA

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    M. Valadan

    2006-08-01

    Full Text Available Preeclampsia is a major cause of morbidity and mortality during pregnancy. Several independent investigators have demonstrated the association of androgens with hypertension. The main purpose of this study was to determine whether maternal levels of sex hormones, especially testosterone, are higher in patients with preeclampsia than in matched normotensive control subjects. Serum levels of testosterone, free testosterone, dehydroepiandrosterone sulfate (DHEA-S and estradiol were measured in 60 subjects in the 3rd trimester of pregnancy with documented preeclampsia (including 30 cases of mild and 30 cases of severe preeclampsia and 60 healthy normotensive women with similar maternal and gestational ages and body mass index (BMI and neonatal sex. All subjects were primigravid with singleton pregnancies. Cases of polycystic ovary (PCO, diabetes, chronic hypertension and chronic systemic diseases such as lupus and patients using steroid hormones and anti-hypertensive drugs were excluded. Levels of testosterone, DHEA-S and estradiol were not higher in primigravid women with preeclampsia than in normotensive women with similar gestational and maternal ages, BMI and neonatal sex. There were no significant differences in sex hormones measured between groups of mild and severe preeclampsia and normotensive women. There were also no significant differences in sex hormone levels according to neonatal sex. These findings are against the hypothesis of mediating or amplifying role of high androgen levels in pathophysiology of preeclampsia.

  16. Relationship of Plasma IL-6 to the Metabolic Measures associated with Insulin Resistance due to Adiposity

    Institute of Scientific and Technical Information of China (English)

    Ryoyu Takeda; Isamu Miyamori; WU Pingsheng (吴平生); Yoshihiro Takayama; Yuji Ito; Takaharu Masunaga; Takahiro Zenda; Satoshi Asaka; Hisanori Oiwake; Kimihide Shinozaki; Yoshiyu Takeda

    2004-01-01

    Objectives To elucidate the relationship of plasma interleukin-6 (IL-6) to the metabolic measures associated with insulin resistance (IR) due to adiposity. Methods For a cross-sectional study, eighty normotensive men with and without obesity were enrolled consecutively in our health examination center. Fasting blood glucose (FBG), fasting plasma immunoreactive insulin (FIRI), HOMA-R (Homeostasis Model Assessment Insulin Resistance Index), plasma lipids (cholesterol, triglyceride, high density lipoprotein cholesterol), cortisol, dehydroepiandrosterone-sulfate (DHEA-S), interleukin-6 and C-reactive protein(CRP) were measured. Results Plasma levels of FIRI, triglyceride (TG), DHEA-S,CRP and HOMA-R were significantly higher in obese group with BMI over 25 than non-obese group,whereas HDL-C was significantly lower in obese group. BMI was positively correlated with FIRI, TG,hsCRP and HOMA-R, whereas negatively with HDLC. BMI was positively correlated with plasma DHEAS levels but not with cortisol. Plasma levels of IL-6 were positively correlated with FIRI, TG, CRP and HOMA-R but in a multiple regression analysis with IL-6, only HOMA-R and TG remained explainable variables. Conclusions Each of commonly used measures of inflammatory reaction, CRP and IL-6, showed a significantly positive correlation with either FIRI or HOMA-R, suggesting associations between subclinical inflammation and obesity as the risk of type 2 diabetes mellitus.

  17. Variability between the follicular steroid hormone levels in different follicles of the same patient and between patients.

    Science.gov (United States)

    Carpintero, Nayara López; Suárez, Onica Armijo; Varea, Carolina González; Rioja, Rubén Gómez; Mangas, Carmen Cuadrado

    2015-01-01

    There is disagreement as to whether the concentration of a substance in follicular fluid is related to the quality of the follicle as a possible reflection of the oocyte quality or whether this concentration is related to the clinical characteristics of the patient. To establish the variability of steroid hormone levels in follicular fluids from different follicles of the same patient and between patients. Prospective cohort study. In 31 patients who underwent intracytoplasmic sperm injection it was performed an ultrasound guided aspiration of follicular fluid of the first two mature follicles from each ovary. Chemiluminescent microparticle immunoassays were performed to determine the levels of estradiol, progesterone, testosterone, and dehydroepiandrosterone sulfate (DHEA-S). Unconditional mixed model. Variation in estradiol levels between follicles in the same patient was approximately twice the variation between subjects (P = 0.05). In the case of progesterone, the intra-subject variation was similar to the inter-subject variation (P = 0.006). The testosterone levels had a slightly smaller intra-subject variation than inter-subject variation (P = 0.002), and the intra-subject variation in DHEA-S levels was approximately one-fifth of the inter-subject variation (P = 0.0003). The variations in the levels of follicular progesterone and testosterone were similar between patients and between a given patient's follicles; however, the estradiol levels variability was higher among different follicles. The amount of follicular estradiol may be considered a selection tool between the follicles of a given patient.

  18. In Silico Investigation of Cytochrome P450 2C9 in relation to Aging Using Traditional Chinese Medicine

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    Tzu-Chieh Hung

    2014-01-01

    Full Text Available Cytochrome P450 2C9 (CYP2C9 metabolizes dehydroepiandrosterone-sulfate (DHEA-S, but in elderly people the amount of DHEA-S remaining after CYP2C9 metabolization may be insufficient for optimal health. A prediction model, molecular docking, and molecular dynamics were used to screen the Traditional Chinese Medicine (TCM database to determine molecular compounds that may inhibit CYP2C9. The candidate compounds apocynoside(I, 4-methoxymagndialdehyde, and prunasin have higher Dock Scores, and prediction bioactivity than warfarin (the control drug. The interaction between 4-methoxymagndialdehyde and CYP2C9 is more intense than with other TCM compounds, but the simulation is longer. In these compounds, apocynoside(I and prunasin have a greater number of pathways for their flexible structure, but these structures create weak interactions. These candidate compounds, which are known to have antioxidation and hypolipidemic functions that have an indirect effect on the aging process, can be extracted from traditional Chinese medicines. Thus, these candidate compounds may become CYP2C9 inhibitors and play an important role in providing optimal health in the elderly.

  19. Changes in Plasma Sex Hormone Levels in Women with Severe Concomitant Injury

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    K. N Yezhova

    2010-01-01

    Full Text Available Objective: to perform a complex study of the plasma levels of 11 sex hormones and their functional values in women with severe concomitant injury (SCI. Subjects and methods. The study enrolled 16 women aged 18—45 years who had SCI. Admission APACHE II scores were 18.9±1.3. According to the outcome of a posttraumatic period, all the patients were divided into 2 groups: A survivors; B deceased subjects. The normal values were used to comparatively analyze the concentrations of reproductive hormones. The time course of changes in hormone concentration was studied on postoperative days 1, 3, and 7. The hormone profile was examined by BSL test kits (USA on a STAT Fax 2100 enzyme immunoanalyzer (Awareness Technology Inc., USA. The content of prolactin, luteinizing hormone, follicle-stimulating hormone, progesterone, 17-hydroxyprogesterone, dehydroepiandrosterone sulfate (DHEA-S, androstendione (A, testosterone (T, dihydrotestosterone, estrone, and estradiol (E were measured. Results. The complex study of changes in the profile of 11 plasma sex hormones was first conducted in women in the posttraumat-ic period. Moreover, the typical plasma hormonal changes were elevated prolactin levels, a decrease in the concentrations of gonadotropins, and increases in some androgens, A, T, and E. The deceased women showed lower concentrations of DHEA-S and T. Analysis revealed an inverse correlation between the plasma concentration of DHEA-S and the injury severity. This change seems to suggest that an adrenal adaptation reaction is exhausted. The changes revealed in hormonal levels are of significance in understanding the pathogenesis of SCT. This may serve as a basis for the development of new therapy modalities using reproductive hormones in the postresuscitative period. Key words: severe concomitant injury, sex hormones, prolactin, luteinizing hormone, follicle-stimulating hormone, progesterone, 17-hydroxyprogesterone, androgens, estrogens.

  20. Associations of Sex Hormones and Anthropometry with the Speaking Voice Profile in the Adult General Population.

    Science.gov (United States)

    Jost, Lasse; Fuchs, Michael; Loeffler, Markus; Thiery, Joachim; Kratzsch, Juergen; Berger, Thomas; Engel, Christoph

    2017-07-21

    There is evidence that sexual hormone concentrations and anthropometric factors influence the human voice. The goal of this study was to investigate to what extent body mass index (BMI), body height, body weight, breast-to-abdomen-ratio, testosterone, estradiol, dehydroepiandrosterone-sulfate (DHEA-S), follicle-stimulating hormone, and luteinizing hormone are associated with the sound pressure level and the fundamental frequency of the speaking voice in a cross-sectional approach among adults in the general population. Speaking voice profiles with four different intensity levels, hormone concentrations, and anthropometric parameters were assessed for 2,381 individuals aged 40-79 years, who were randomly sampled from the population of a large city in Germany. Multivariate analysis was performed, adjusting for age and stratified by sex. Taller body height was associated with lower frequencies. Higher body weight was associated with lower frequencies and higher sound pressure levels. The ratio of chest to abdominal circumference was associated with the sound pressure levels in males and females: participants with larger breast-to-abdomen-ratio were found to have higher sound pressure levels. Among the sexual hormones, higher concentrations of DHEA-S were associated with lower fundamental frequencies of the voice while using the normal speaking voice. In addition, bioavailable testosterone was associated with the sound pressure level of the normal speaking voice in men and the softest speaking voice in women. Our findings suggest that BMI, body height, body weight, breast-to-abdomen-ratio, bioavailable testosterone, and DHEA-S are associated with the speaking voice in adults. No associations between testosterone and the frequency of the speaking voice were found. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

  1. 21 CFR 184.1307 - Ferric sulfate.

    Science.gov (United States)

    2010-04-01

    ... Substances Affirmed as GRAS § 184.1307 Ferric sulfate. (a) Ferric sulfate (iron (III) sulfate, Fe2(SO4)3 CAS Reg. No. 10028-22-5) is a yellow substance that may be prepared by oxidizing iron (II) sulfate or by treating ferric oxide or ferric hydroxide with sulfuric acid. (b) The ingredient must be of a...

  2. 21 CFR 558.364 - Neomycin sulfate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Neomycin sulfate. 558.364 Section 558.364 Food and... in Animal Feeds § 558.364 Neomycin sulfate. (a) Approvals. Type A medicated article: 325 grams per.... (c) (d) Conditions of use. Neomycin sulfate is used as follows: Neomycin Sulfate...

  3. The novel dehydroepiandrosterone (DHEA) derivative BNN27 counteracts delay-dependent and scopolamine-induced recognition memory deficits in rats.

    Science.gov (United States)

    Pitsikas, Nikolaos; Gravanis, Achille

    2017-04-01

    Experimental evidence indicates that the neurosteroids dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulphate (DHEAS) are involved in cognition. BNN27 is a novel 17C spiroepoxy-DHEA derivative, which devoid of steroidogenic activity. The neuroprotective effects of BNN27 have been recently reported. The present study was designed to investigate the effects of BNN27 on recognition memory in rats. For this purpose, the novel object task (NOT), a procedure assessing non-spatial recognition memory and the novel location task (NLT), a procedure evaluating spatial recognition memory were used. Intraperitoneal (i.p.) administration of BNN27 (3 and 10mg/kg) antagonized delay-dependent deficits in the NOT in the normal rat, suggesting that this DHEA derivative affected acquisition, storage and retrieval of information. In addition, BNN27 (3 and 10mg/kg, i.p.) counteracted the scopolamine [0.2mg/kg, subcutaneously (s.c.)]-induced non-spatial and spatial recognition memory deficits. These findings suggest that BNN27 may modulate different aspects of recognition memory, potentially interacting with the cholinergic system, relevant to cognition. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Effect of dehydroepiandrosterone administration on fatigue, well-being, and functioning in women with primary Sjogren syndrome : a randomised controlled trial

    NARCIS (Netherlands)

    Hartkamp, A.; Geenen, R.; Godaert, G. L. R.; Bootsma, H.; Kruize, A. A.; Bijlsma, J. W. J.; Derksen, R. H. W. M.

    Objective: Dehydroepiandrosterone (DHEA) administration has been reported to improve fatigue, psychological distress, and physical disability. These are common features of primary Sjogren syndrome (pSS). We investigated the effects of DHEA administration on fatigue, well-being, and functioning in

  5. Severity of murine collagen-induced arthritis correlates with increased CYP7B activity : enhancement of dehydroepiandrosterone metabolism by interleukin-1 beta

    NARCIS (Netherlands)

    Dulos, J; Verbraak, E; Bagchus, WM; Boots, AMH; Kaptein, A

    2004-01-01

    Objective. The endogenous steroid dehydroepiandrosterone (DHEA) has been reported to play a role in rheumatoid arthritis (RA). DHEA is metabolized by the P450 enzyme CYP7B into 7alpha-OH-DHEA, which has immunostimulating properties. This study was undertaken to investigate the putative role of CYP7B

  6. Effect of dehydroepiandrosterone administration on fatigue, well-being, and functioning in women with primary Sjogren syndrome : a randomised controlled trial

    NARCIS (Netherlands)

    Hartkamp, A.; Geenen, R.; Godaert, G. L. R.; Bootsma, H.; Kruize, A. A.; Bijlsma, J. W. J.; Derksen, R. H. W. M.

    2008-01-01

    Objective: Dehydroepiandrosterone (DHEA) administration has been reported to improve fatigue, psychological distress, and physical disability. These are common features of primary Sjogren syndrome (pSS). We investigated the effects of DHEA administration on fatigue, well-being, and functioning in wo

  7. Feasibility of a liver transcriptomics approach to assess bovine treatment with the prohormone dehydroepiandrosterone (DHEA).

    Science.gov (United States)

    Rijk, Jeroen C W; Peijnenburg, Ad A C M; Hendriksen, Peter J M; Van Hende, Johan M; Groot, Maria J; Nielen, Michel W F

    2010-09-16

    Within the European Union the use of growth promoting agents in animal production is prohibited. Illegal use of natural prohormones like dehydroepiandrosterone (DHEA) is hard to prove since prohormones are strongly metabolized in vivo. In the present study, we investigated the feasibility of a novel effect-based approach for monitoring abuse of DHEA. Changes in gene expression profiles were studied in livers of bull calves treated orally (PO) or intramuscularly (IM) with 1000 mg DHEA versus two control groups, using bovine 44K DNA microarrays. In contrast to controlled genomics studies, this work involved bovines purchased at the local market on three different occasions with ages ranging from 6 to 14 months, thereby reflecting the real life inter-animal variability due to differences in age, individual physiology, season and diet. As determined by principal component analysis (PCA), large differences in liver gene expression profiles were observed between treated and control animals as well as between the two control groups. When comparing the gene expression profiles of PO and IM treated animals to that of all control animals, the number of significantly regulated genes (p-value 1.5) was 23 and 37 respectively. For IM and PO treated calves, gene sets were generated of genes that were significantly regulated compared to one control group and validated versus the other control group using Gene Set Enrichment Analysis (GSEA). This cross validation, showed that 6 out of the 8 gene sets were significantly enriched in DHEA treated animals when compared to an 'independent' control group. This study showed that identification and application of genomic biomarkers for screening of (pro)hormone abuse in livestock production is substantially hampered by biological variation. On the other hand, it is demonstrated that comparison of pre-defined gene sets versus the whole genome expression profile of an animal allows to distinguish DHEA treatment effects from variations in

  8. Detection of dehydroepiandrosterone misuse by means of gas chromatography- combustion-isotope ratio mass spectrometry.

    Science.gov (United States)

    Mareck, Ute; Geyer, Hans; Flenker, Ulrich; Piper, Thomas; Thevis, Mario; Schänzer, Wilhelm

    2007-01-01

    According to World Anti-Doping Agency (WADA) rules (WADA Technical Document-TD2004EAAS) urine samples containing dehydroepiandrosterone (DHEA) concentrations greater than 100 ng ML(-1) shall be submitted to isotope ratio mass spectrometry (IRMS) analysis. The threshold concentration is based on the equivalent to the glucuronide, and the DHEA concentrations have to be adjusted for a specific gravity value of 1.020. In 2006, 11,012 doping control urine samples from national and international federations were analyzed in the Cologne doping control laboratory, 100 (0.9%) of them yielding concentrations of DHEA greater than 100 ng mL(-1). Sixty-eight percent of the specimens showed specific gravity values higher than 1.020, 52% originated from soccer players, 95% were taken in competition, 85% were male urines, 99% of the IRMS results did not indicate an application of testosterone or related prohormones. Only one urine sample was reported as an adverse analytical finding having 319 ng mL(-1) DHEA (screening result), more than 10,000 ng mL(-1) androsterone and depleted carbon isotope ratio values for the testosterone metabolites androsterone and etiocholanolone. Statistical evaluation showed significantly different DHEA concentrations between specimens taken in- and out-of- competition, whereas females showed smaller DHEA values than males for both types of control. Also a strong influence of the DHEA excretion on different sport disciplines was detectable. The highest DHEA values were detected for game sports (soccer, basketball, handball, ice hockey), followed by boxing and wrestling. In 2007, 6622 doping control urine samples were analyzed for 3alpha,5-cyclo-5alpha-androstan-6beta-ol-17-one (3alpha,5-cyclo), a DHEA metabolite which was described as a useful gas chromatography-mass spectrometry (GC-MS) screening marker for DHEA abuse. Nineteen urine specimens showed concentrations higher than the suggested threshold of 140 ng mL(-1), six urine samples yielded

  9. Bioengineered heparins and heparan sulfates.

    Science.gov (United States)

    Fu, Li; Suflita, Matthew; Linhardt, Robert J

    2016-02-01

    Heparin and heparan sulfates are closely related linear anionic polysaccharides, called glycosaminoglycans, which exhibit a number of important biological and pharmacological activities. These polysaccharides, having complex structures and polydispersity, are biosynthesized in the Golgi of animal cells. While heparan sulfate is a widely distributed membrane and extracellular glycosaminoglycan, heparin is found primarily intracellularly in the granules of mast cells. While heparin has historically received most of the scientific attention for its anticoagulant activity, interest has steadily grown in the multi-faceted role heparan sulfate plays in normal and pathophysiology. The chemical synthesis of these glycosaminoglycans is largely precluded by their structural complexity. Today, we depend on livestock animal tissues for the isolation and the annual commercial production of hundred ton quantities of heparin used in the manufacture of anticoagulant drugs and medical device coatings. The variability of animal-sourced heparin and heparan sulfates, their inherent impurities, the limited availability of source tissues, the poor control of these source materials and their manufacturing processes, suggest a need for new approaches for their production. Over the past decade there have been major efforts in the biotechnological production of these glycosaminoglycans, driven by both therapeutic applications and as probes to study their natural functions. This review focuses on the complex biology of these glycosaminoglycans in human health and disease, and the use of recombinant technology in the chemoenzymatic synthesis and metabolic engineering of heparin and heparan sulfates. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Heparan sulfate structure: methods to study N-sulfation and NDST action.

    Science.gov (United States)

    Dagälv, Anders; Lundequist, Anders; Filipek-Górniok, Beata; Dierker, Tabea; Eriksson, Inger; Kjellén, Lena

    2015-01-01

    Heparan sulfate proteoglycans are important modulators of cellular processes where the negatively charged polysaccharide chains interact with target proteins. The sulfation pattern of the heparan sulfate chains will determine the proteins that will bind and the affinity of the interactions. The N-deacetylase/N-sulfotransferase (NDST) enzymes are of key importance during heparan sulfate biosynthesis when the sulfation pattern is determined. In this chapter, metabolic labeling of heparan sulfate with [(35)S]sulfate or [(3)H]glucosamine in cell cultures is described, in addition to characterization of polysaccharide chain length and degree of N-sulfation. Methods to measure NDST enzyme activity are also presented.

  11. Studies on Sulfation of Lycium barbarum Polysaccharides

    Institute of Scientific and Technical Information of China (English)

    YI,Jian-Ping; YAN,Hong; ZHONG,Ru-Gang

    2004-01-01

    @@ Polysaccharides can anti-virus, such as human immunodeficiency virus (HIV-1),[1] herpes simplex virus (HSV-1,HSV-2) and cytomegalovirus. Some of them are sulfates, e.g. dextran sulfate, heparin, sulfonation of chitosan and sulfated derivatives of Lentinan. Our results showed that sulfated derivatives of Lycium barbarum polysaccharides (LBP)have anti-HIV activity. Because the anti-HIV activity of LBP was deeply dependent on the molecular weight, the sulfation pattern and glycosidic branches besides degree of sulfation (DS), so we emphasized our work on the factors of DS.

  12. Sulfate reduction in freshwater peatlands

    Energy Technology Data Exchange (ETDEWEB)

    Oequist, M.

    1996-12-31

    This text consist of two parts: Part A is a literature review on microbial sulfate reduction with emphasis on freshwater peatlands, and part B presents the results from a study of the relative importance of sulfate reduction and methane formation for the anaerobic decomposition in a boreal peatland. The relative importance of sulfate reduction and methane production for the anaerobic decomposition was studied in a small raised bog situated in the boreal zone of southern Sweden. Depth distribution of sulfate reduction- and methane production rates were measured in peat sampled from three sites (A, B, and C) forming an minerotrophic-ombrotrophic gradient. SO{sub 4}{sup 2-} concentrations in the three profiles were of equal magnitude and ranged from 50 to 150 {mu}M. In contrast, rates of sulfate reduction were vastly different: Maximum rates in the three profiles were obtained at a depth of ca. 20 cm below the water table. In A it was 8 {mu}M h{sup -1} while in B and C they were 1 and 0.05 {mu}M h{sup -1}, respectively. Methane production rates, however, were more uniform across the three nutrient regimes. Maximum rates in A (ca. 1.5 {mu}g d{sup -1} g{sup -1}) were found 10 cm below the water table, in B (ca. 1.0 {mu}g d{sup -1} g{sup -1}) in the vicinity of the water table, and in C (0.75 {mu}g d{sup -1} g{sup -1}) 20 cm below the water table. In all profiles both sulfate reduction and methane production rates were negligible above the water table. The areal estimates of methane production for the profiles were 22.4, 9.0 and 6.4 mmol m{sup -2} d{sup -1}, while the estimates for sulfate reduction were 26.4, 2.5, and 0.1 mmol m{sup -2} d{sup -1}, respectively. The calculated turnover times at the sites were 1.2, 14.2, and 198.7 days, respectively. The study shows that sulfate reducing bacteria are important for the anaerobic degradation in the studied peatland, especially in the minerotrophic sites, while methanogenic bacteria dominate in ombrotrophic sites Examination

  13. The acute effect of dexamethasone on plasma leptin concentrations and the relationships between fasting leptin, the IGF-I/IGFBP system, dehydroepiandrosterone, androstenedione and testosterone in an elderly population

    NARCIS (Netherlands)

    Janssen, JAMJL; Huizenga, NATM; Stolk, RP; Grobbee, DE; Pols, HAP; de Jong, FH; Attanasio, AMF; Blum, WF; Lamberts, SWJ

    OBJECTIVE To investigate the acute effect of dexamethasone administration on serum leptin levels and the relationships between dehydroepiandrosterone (DHEAS), androstenedione, testosterone and the IGF-I/IGFBP system and leptin levels in healthy elderly humans. METHODS In 209 healthy elderly

  14. Oxidative metabolism of dehydroepiandrosterone (DHEA) and biologically active oxygenated metabolites of DHEA and epiandrosterone (EpiA)--recent reports.

    Science.gov (United States)

    El Kihel, Laïla

    2012-01-01

    Dehydroepiandrosterone (DHEA) is a multifunctional steroid with a broad range of biological effects in humans and animals. DHEA can be converted to multiple oxygenated metabolites in the brain and peripheral tissues. The mechanisms by which DHEA exerts its effects are not well understood. However, evidence that the effects of DHEA are mediated by its oxygenated metabolites has accumulated. This paper will review the panel of oxygenated DHEA metabolites (7, 16 and 17-hydroxylated derivatives) including a number of 5α-androstane derivatives, such as epiandrosterone (EpiA) metabolites. The most important aspects of the oxidative metabolism of DHEA in the liver, intestine and brain are described. Then, this article reviews the reported biological effects of oxygenated DHEA metabolites from recent findings with a specific focus on cancer, inflammatory and immune processes, osteoporosis, thermogenesis, adipogenesis, the cardiovascular system, the brain and the estrogen and androgen receptors. Copyright © 2011 Elsevier Inc. All rights reserved.

  15. Dehydroepiandrosterone activates AMP kinase and regulates GLUT4 and PGC-1α expression in C2C12 myotubes

    Energy Technology Data Exchange (ETDEWEB)

    Yokokawa, Takumi [Laboratory of Sports and Exercise Medicine, Graduate School of Human and Environmental Studies, Kyoto University, Kyoto (Japan); Sato, Koji [Graduate School of Sport & Health Science, Ritsumeikan University, Shiga (Japan); Iwanaka, Nobumasa [The Graduate School of Science and Engineering, Ritsumeikan University, Shiga (Japan); Honda, Hiroki [Graduate School of Sport & Health Science, Ritsumeikan University, Shiga (Japan); Higashida, Kazuhiko [Faculty of Sport Science, Waseda University, Saitama (Japan); Iemitsu, Motoyuki [Graduate School of Sport & Health Science, Ritsumeikan University, Shiga (Japan); Hayashi, Tatsuya [Laboratory of Sports and Exercise Medicine, Graduate School of Human and Environmental Studies, Kyoto University, Kyoto (Japan); Hashimoto, Takeshi, E-mail: thashimo@fc.ritsumei.ac.jp [Graduate School of Sport & Health Science, Ritsumeikan University, Shiga (Japan)

    2015-07-17

    Exercise and caloric restriction (CR) have been reported to have anti-ageing, anti-obesity, and health-promoting effects. Both interventions increase the level of dehydroepiandrosterone (DHEA) in muscle and blood, suggesting that DHEA might partially mediate these effects. In addition, it is thought that either 5′-adenosine monophosphate-activated protein kinase (AMPK) or peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) mediates the beneficial effects of exercise and CR. However, the effects of DHEA on AMPK activity and PGC-1α expression remain unclear. Therefore, we explored whether DHEA in myotubes acts as an activator of AMPK and increases PGC-1α. DHEA exposure increased glucose uptake but not the phosphorylation levels of Akt and PKCζ/λ in C2C12 myotubes. In contrast, the phosphorylation levels of AMPK were elevated by DHEA exposure. Finally, we found that DHEA induced the expression of the genes PGC-1α and GLUT4. Our current results might reveal a previously unrecognized physiological role of DHEA; the activation of AMPK and the induction of PGC-1α by DHEA might mediate its anti-obesity and health-promoting effects in living organisms. - Highlights: • We assessed whether dehydroepiandrosterone (DHEA) activates AMPK and PGC-1α. • DHEA exposure increased glucose uptake in C2C12 myotubes. • The phosphorylation levels of AMPK were elevated by DHEA exposure. • DHEA induced the expression of the genes PGC-1α and GLUT4. • AMPK might mediate the anti-obesity and health-promoting effects of DHEA.

  16. A sulfate conundrum: Dissolved sulfates of deep-saline brines and carbonate-associated sulfates

    Science.gov (United States)

    Labotka, Dana M.; Panno, Samuel V.; Locke, Randall A.

    2016-10-01

    Sulfates in deeply circulating brines and carbonate-associated sulfates (CAS) within sedimentary units of the Cambrian strata in the Illinois Basin record a complex history. Dissolved sulfate within the Mt. Simon Sandstone brines exhibits average δ34SSO4 values of 35.4‰ and δ18OSO4 values of 14.6‰ and appears to be related to Cambrian seawater sulfate, either original seawater or sourced from evaporite deposits such as those in the Michigan Basin. Theoretical and empirical relationships based on stable oxygen isotope fractionation suggest that sulfate within the lower depths of the Mt. Simon brines has experienced a long period of isolation, possibly several tens of millions of years. Comparison with brines from other stratigraphic units shows the Mt. Simon brines are geochemically unique. Dissolved sulfate from brines within the Ironton-Galesville Sandstone averages 22.7‰ for δ34SSO4 values and 13.0‰ for δ18OSO4 values. The Ironton-Galesville brine has mixed with younger groundwater, possibly of Ordovician to Devonian age and younger. The Eau Claire Formation lies between the Mt. Simon and Ironton-Galesville Sandstones. The carbonate units of the Eau Claire and stratigraphically equivalent Bonneterre Formation contain CAS that appears isotopically related to the Late Pennsylvanian-Early Permian Mississippi Valley-type ore pulses that deposited large sulfide minerals in the Viburnum Trend/Old Lead Belt ore districts. The δ34SCAS values range from 21.3‰ to 9.3‰, and δ18OCAS values range from +1.4‰ to -2.6‰ and show a strong covariance (R2 = 0.94). The largely wholesale replacement of Cambrian seawater sulfate signatures in these dolomites does not appear to have affected the sulfate signatures in the Mt. Simon brines even though these sulfide deposits are found in the stratigraphically equivalent Lamotte Sandstone to the southwest. On the basis of this and previous studies, greater fluid densities of the Mt. Simon brines may have prevented the

  17. Sulfate transport in toad skin

    DEFF Research Database (Denmark)

    Larsen, Erik Hviid; Simonsen, K

    1988-01-01

    1. In short-circuited toad skin preparations exposed bilaterally to NaCl-Ringer's containing 1 mM SO2(-4), influx of sulfate was larger than efflux showing that the skin is capable of transporting sulfate actively in an inward direction. 2. This active transport was not abolished by substituting...... apical Na+ for K+. 3. Following voltage activation of the passive Cl- permeability of the mitochondria-rich (m.r.) cells sulfate flux-ratio increased to a value predicted from the Ussing flux-ratio equation for a monovalent anion. 4. In such skins, which were shown to exhibit vanishingly small leakage...... conductances, the variation of the rate coefficient for sulfate influx (y) was positively correlated with the rate coefficient for Cl- influx (x), y = 0.035 x - 0.0077 cm/sec (r = 0.9935, n = 15). 5. Addition of the phosphodiesterase inhibitor, 3-isobutyl-1-methyl-xanthine to the serosal bath of short...

  18. Sulfation of thyroid hormone by estrogen sulfotransferase

    NARCIS (Netherlands)

    M.H.A. Kester (Monique); T.J. Visser (Theo); C.H. van Dijk (Caren); D. Tibboel (Dick); A.M. Hood (Margaret); N.J. Rose; W. Meinl; U. Pabel; H. Glatt; C.N. Falany; M.W. Coughtrie

    1999-01-01

    textabstractSulfation is one of the pathways by which thyroid hormone is inactivated. Iodothyronine sulfate concentrations are very high in human fetal blood and amniotic fluid, suggesting important production of these conjugates in utero. Human estrogen sulfotransferas

  19. Sulfation of thyroid hormone by estrogen sulfotransferase

    NARCIS (Netherlands)

    M.H.A. Kester (Monique); T.J. Visser (Theo); C.H. van Dijk (Caren); D. Tibboel (Dick); A.M. Hood (Margaret); N.J. Rose; W. Meinl; U. Pabel; H. Glatt; C.N. Falany; M.W. Coughtrie

    1999-01-01

    textabstractSulfation is one of the pathways by which thyroid hormone is inactivated. Iodothyronine sulfate concentrations are very high in human fetal blood and amniotic fluid, suggesting important production of these conjugates in utero. Human estrogen sulfotransferas

  20. Sulfation of thyroid hormone by estrogen sulfotransferase

    NARCIS (Netherlands)

    M.H.A. Kester (Monique); T.J. Visser (Theo); C.H. van Dijk (Caren); D. Tibboel (Dick); A.M. Hood (Margaret); N.J. Rose; W. Meinl; U. Pabel; H. Glatt; C.N. Falany; M.W. Coughtrie

    1999-01-01

    textabstractSulfation is one of the pathways by which thyroid hormone is inactivated. Iodothyronine sulfate concentrations are very high in human fetal blood and amniotic fluid, suggesting important production of these conjugates in utero. Human estrogen

  1. Sulfate-rich Archean Oceans

    Science.gov (United States)

    Brainard, J. L.; Choney, A. P.; Ohmoto, H.

    2012-12-01

    There is a widely held belief that prior to 2.4 Ga, the Archean oceans and atmosphere were reducing, and therefore sulfate poor (concentrations 100 m), widely distributed (> km2), and contain only minor amounts of sulfides. These barite beds may have developed from reactions between Ba-rich hydrothermal fluids and evaporate bodies. Simple mass balance calculations suggest that the sulfate contents of the pre-evaporitic seawater must have been greater than ~1 mM. Some researchers have suggested that the SO4 for these beds was derived from the hydrolysis of SO2-rich magmatic fluids. However, this was unlikely as the reaction, 4SO2 + 4H2O → 3H2SO4 + H2S would have produced large amounts of sulfide, as well as sulfate minerals. Many Archean-aged volcanogenic massive sulfide (VMS) deposits, much like those of the younger ages, record evidence for abundant seawater sulfate. As VMS deposits are most likely formed by submarine hydrothermal fluids that developed from seawater circulating through the seafloor rock, much of the seawater sulfate is reduced to from sulfides at depths. However, some residual sulfate in the hydrothermal fluids, with or without the addition of sulfate from the local seawater, can form sulfate minerals such as barite at near the seafloor. The d34S relationships between barites and pyrites in the Archean VMS deposits are similar to those of the younger VMS deposits, except for the lower d34S values for the seawater SO4. The abundance of pyrite in Archean black shales is also evidence of sulfate rich seawater. Pyrites in Archean-aged black shales were most likely the products of either bacterial or thermochemical sulfate reduction during diagenesis of the sediments. Their abundance in sedimentary rocks is determined by: (a) the availability of reactive carbon; (b) the availability of reactive Fe (Fe3+ hydroxides and Fe2+-rich pore fluid); (c) the sedimentation rate; and (d) the flux of SO42- in the sediments, which depends on the seawater SO42

  2. 21 CFR 524.1484e - Neomycin sulfate and polymyxin B sulfate ophthalmic solution.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Neomycin sulfate and polymyxin B sulfate ophthalmic solution. 524.1484e Section 524.1484e Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... DOSAGE FORM NEW ANIMAL DRUGS § 524.1484e Neomycin sulfate and polymyxin B sulfate ophthalmic solution....

  3. 21 CFR 582.1643 - Potassium sulfate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Potassium sulfate. 582.1643 Section 582.1643 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1643 Potassium sulfate. (a) Product. Potassium sulfate. (b) Conditions of use....

  4. 21 CFR 184.1643 - Potassium sulfate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Potassium sulfate. 184.1643 Section 184.1643 Food... Specific Substances Affirmed as GRAS § 184.1643 Potassium sulfate. (a) Potassium sulfate (K2SO4, CAS Reg... having a bitter, saline taste. It is prepared by the neutralization of sulfuric acid with...

  5. 21 CFR 582.5443 - Magnesium sulfate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Magnesium sulfate. 582.5443 Section 582.5443 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Supplements 1 § 582.5443 Magnesium sulfate. (a) Product. Magnesium sulfate. (b) Conditions of use....

  6. 21 CFR 184.1443 - Magnesium sulfate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Magnesium sulfate. 184.1443 Section 184.1443 Food... Specific Substances Affirmed as GRAS § 184.1443 Magnesium sulfate. (a) Magnesium sulfate (MgSO4·7H2O, CAS... magnesium oxide, hydroxide, or carbonate with sulfuric acid and evaporating the solution to...

  7. Sulfate transport in Penicillium chrysogenum plasma membranes.

    OpenAIRE

    Hillenga, Dirk J.; Versantvoort, Hanneke J.M.; Driessen, Arnold J. M.; Konings, Wil N.

    1996-01-01

    Transport studies with Penicillium chrysogenum plasma membranes fused with cytochrome c oxidase liposomes demonstrate that sulfate uptake is driven by the transmembrane pH gradient and not by the transmembrane electrical potential. Ca2+ and other divalent cations are not required. It is concluded that the sulfate transport system catalyzes the symport of two protons with one sulfate anion.

  8. Sulfate-reducing prokaryotes in river floodplains

    NARCIS (Netherlands)

    Miletto, M.

    2007-01-01

    This thesis constitutes a pioneer attempt at elucidating the ecology of sulfate-reducing prokaryotes in river floodplains. These are non-typical sulfate-reducing environmental settings, given the generally low sulfate concentration that characterize freshwater habitats, and river flow regulation

  9. 21 CFR 582.5315 - Ferrous sulfate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Ferrous sulfate. 582.5315 Section 582.5315 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Supplements 1 § 582.5315 Ferrous sulfate. (a) Product. Ferrous sulfate. (b) Conditions of use. This substance...

  10. 21 CFR 582.5461 - Manganese sulfate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Manganese sulfate. 582.5461 Section 582.5461 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Supplements 1 § 582.5461 Manganese sulfate. (a) Product. Manganese sulfate. (b) Conditions of use....

  11. 21 CFR 184.1461 - Manganese sulfate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Manganese sulfate. 184.1461 Section 184.1461 Food... Specific Substances Affirmed as GRAS § 184.1461 Manganese sulfate. (a) Manganese sulfate (MnSO4·H2O, CAS... manganese compounds with sulfuric acid. It is also obtained as a byproduct in the manufacture...

  12. Tris(ethylenediaminecobalt(II sulfate

    Directory of Open Access Journals (Sweden)

    Bunlawee Yotnoi

    2010-06-01

    Full Text Available The structure of the title compound, [CoII(C2H8N23]SO4, the cobalt example of [M(C2H8N23]SO4, is reported. The Co and S atoms are located at the 2d and 2c Wyckoff sites (point symmetry 32, respectively. The Co atom is coordinated by six N atoms of three chelating ethylenediamine molecules generated from half of the ethylenediamine molecule in the asymmetric unit. The O atoms of the sulfate anion are disordered mostly over two crystallographic sites. The third disorder site of O (site symmetry 3 has a site occupancy approaching zero. The H atoms of the ethylenediamine molecules interact with the sulfate anions via intermolecular N—H...O hydrogen-bonding interactions.

  13. Changes in the Plasma Sex Hormone Profile in Males with Severe Concomitant Injury

    Directory of Open Access Journals (Sweden)

    K. N Yezhova

    2009-01-01

    Full Text Available Objective: to perform a complex study of typical plasma sex hormone changes and their functional significance in males with severe concomitant injury (SCI. Subjects and methods. Fifty-nine males aged 18—49 years who had SCI were enrolled in the study. The admission severity was an APACHE II score of 18.6±2.4. According to the outcome of the disease, all the patients were divided into 2 groups: A survivors; B deceased persons. A control comprised 12 healthy male donors aged 19-36 years, in whom the levels of 8 sex steroids were measured. The standard procedures were used to comparatively analyze the concentrations of pituitary reproductive hormones and aldosterone. Hormonal concentrations were studied over time on posttraumatic days 1, 3, 5, 7, 10, and 15. The plasma hormone profile was examined by test kits (BSL, USA on a Stat Fax 2100 device (Awareness Technology Inc., USA for enzyme immunoassay. Prolactin, luteinizing hormone (LH, follicle-stimulating hormone (FSH, progesterone (P, 17-hydroxyprogesterone (17-OH-P, dehydroepiandrosterone sulfate (DHEA-S, androstendione (A, testosterone (T, dihydrotestosterone (DHT, estrone (E1, estradiol (E2, and aldosterone were determined. Results. The complex study of phasic changes in the profile of 11 plasma sex hormones was first conducted in males in the posttraumatic period. Moreover, the typical plasma hormonal changes were elevated prolactin levels and their phasic variations, normal LH and FSH levels with a tendency for further phasic LH changes and FSH reduction. After the injury, the plasma concentration of P was increased and that of 17-OH-P was decreased. The levels of A and DHEA-S varied in the normal range with a tendency for DHEA-S to be lower during the process. In the posttraumatic period, the plasma content of T and DHT was substantially reduced and that of E1 and E2 was increased. The deceased patients generally showed higher levels of A, DHEA-S, and estrogens as a reflection of

  14. Administration of Dehydroepiandrosterone (DHEA) Increases Serum Levels of Androgens and Estrogens But Does Not Enhance Short-term Memory in Post-Menopausal Women

    OpenAIRE

    Merritt, Paul; Stangl, Bethany; Hirshman, Elliot; Verbalis, Joseph

    2012-01-01

    The current study examines the effect of administering dehydroepiandrosterone (DHEA) on short-term memory. This experiment used a double-blind placebo-controlled cross-over design to explore the effects of a four week regimen of 50 mg oral DHEA on performance on the digit span, verbal span, and Modified Sternberg (Oberauer) tasks. The results demonstrate that the current regimen of drug administration significantly increases serum levels of DHEA, DHEAS, testosterone and estrone and substantia...

  15. Effect of Interleukin-1beta and Dehydroepiandrosterone on the Expression of Lumican and Fibromodulin in Fibroblast-Like Synovial Cells of the Human Temporomandibular Joint

    OpenAIRE

    Okamoto, K; Kiga, N.; Shinohara, Y.; Tojyo, I.; Fujita, S.

    2015-01-01

    Several epidemiological studies have reported that temporomandibular disorders (TMDs) are more prevalent in women than in men. It has recently been proposed that sex hormones such as estrogen, testosterone and dehydroepiandrosterone (DHEA) are involved with the pathogenesis of TMDs. Although studies have investigated the relationship between estrogen and testosterone and the restoration of TMDs, the relationship between DHEA and TMDs is unknown. The synovial tissue of the temporomandibular jo...

  16. Effect of interleukin-1beta and dehydroepiandrosterone on the expression of lumican and fibromodulin in fibroblast-like synovial cells of the human temporomandibular joint

    OpenAIRE

    Okamoto, K; Kiga, N.; Shinohara, Y.; Tojyo, I.; Fujita, S.

    2015-01-01

    Several epidemiological studies have reported that temporomandibular disorders (TMDs) are more prevalent in women than in men. It has recently been proposed that sex hormones such as estrogen, testosterone and dehydroepiandrosterone (DHEA) are involved with the pathogenesis of TMDs. Although studies have investigated the relationship between estrogen and testosterone and the restoration of TMDs, the relationship between DHEA and TMDs is unknown. The synovial tissue of the temporomandibular jo...

  17. Sulfates on Mars: Indicators of Aqueous Processes

    Science.gov (United States)

    Bishop, Janice L.; Lane, Melissa D.; Dyar, M. Darby; Brown, Adrian J.

    2006-01-01

    Recent analyses by MER instruments at Meridiani Planum and Gusev crater and the OMEGA instrument on Mars Express have provided detailed information about the presence of sulfates on Mars [1,2,3]. We are evaluating these recent data in an integrated multi-disciplinary study of visible-near-infrared, mid-IR and Mossbauer spectra of several sulfate minerals and sulfate-rich analog sites. Our analyses suggest that hydrated iron sulfates may account for features observed in Mossbauer and mid-IR spectra of Martian soils [4]. The sulfate minerals kieserite, gypsum and other hydrated sulfates have been identified in OMEGA spectra in the layered terrains in Valles Marineris and Terra Meridiani [2]. These recent discoveries emphasize the importance of studying sulfate minerals as tracers of aqueous processes. The sulfate-rich rock outcrops observed in Meridiani Planum may have formed in an acidic environment similar to acid rock drainage environments on Earth [5]. Because microorganisms typically are involved in the oxidation of sulfides to sulfates in terrestrial sites, sulfate-rich rock outcrops on Mars may be a good location to search for evidence of past life on that planet. Whether or not life evolved on Mars, following the trail of sulfate minerals will lead to a better understanding of aqueous processes and chemical weathering.

  18. Chondroitin Sulfate Perlecan Enhances Collagen Fibril Formation

    DEFF Research Database (Denmark)

    Kvist, A. J.; Johnson, A. E.; Mörgelin, M.

    2006-01-01

    produced in the presence of perlecan. Interestingly, the enhancement of collagen fibril formation is independent on the core protein and is mimicked by chondroitin sulfate E but neither by chondroitin sulfate D nor dextran sulfate. Furthermore, perlecan chondroitin sulfate contains the 4,6-disulfated......Inactivation of the perlecan gene leads to perinatal lethal chondrodysplasia. The similarity to the phenotypes of the Col2A1 knock-out and the disproportionate micromelia mutation suggests perlecan involvement in cartilage collagen matrix assembly. We now present a mechanism for the defect...... in collagen type II fibril assembly by perlecan-null chondrocytes. Cartilage perlecan is a heparin sulfate or a mixed heparan sulfate/chondroitin sulfate proteoglycan. The latter form binds collagen and accelerates fibril formation in vitro, with more defined fibril morphology and increased fibril diameters...

  19. Synthesis and biological evaluation of esters of 16-formyl-17-methoxy-dehydroepiandrosterone derivatives as inhibitors of 5α-reductase type 2.

    Science.gov (United States)

    Sánchez-Márquez, Araceli; Arellano, Yazmín; Bratoeff, Eugene; Heuze, Yvonne; Córdova, Karen; Nieves, Gladys; Soriano, Juan; Cabeza, Marisa

    2016-12-01

    In this study, we investigated the in vitro effect of 16-formyl-17-methoxy dehydroepiandrosterone derivatives on the activity of 5α-reductase type 2 (5α-R2) obtained from human prostate. The activity of different concentrations of these derivatives was determined for the conversion of labelled testosterone to dihydrotestosterone. The results indicated that an aliphatic ester moiety at the C-3 position of these derivatives increases their in vitro potency as inhibitors of 5α-R2 activity compared to finasteride®, which is considered to be a potent inhibitor of 5α-R2. In this case, the augmentation of the lipophilicity of these dehydroepiandrosterone derivatives increased their potency as inhibitors of 5α-R2. However, the presence of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl rings as the cycloaliphatic ester moiety at C-3 of the formyl methoxy dehydroepiandrosterone scaffold did not inhibit the activity of this enzyme. This may be due to the presence of steric factors between the enzyme and the spatial structure of these derivatives.

  20. Sulfation and biological activities of konjac glucomannan.

    Science.gov (United States)

    Bo, Surina; Muschin, Tegshi; Kanamoto, Taisei; Nakashima, Hideki; Yoshida, Takashi

    2013-05-15

    The sulfation of konjac glucomannan and its anti-HIV and blood anticoagulant activities were investigated. Konjac glucomannan is a polysaccharide occurring naturally in konjac plant tubers and has high molecular weights. Solubility in water is very low, and the aqueous solutions at low concentrations have high viscosity. Before sulfation, hydrolysis by diluted sulfuric acid was carried out to decrease the molecular weights of M¯n=19.2 × 10(4)-0.2 × 10(4). Sulfation with piperidine-N-sulfonic acid or SO3-pyridine complex gave sulfated konjac glucomannans with molecular weights of M¯n=1.0 × 10(4)-0.4 × 10(4) and degrees of sulfation (DS) of 1.3-1.4. It was found that the sulfated konjac glucomannans had potent anti-HIV activity at a 50% effective concentration, (EC50) of 1.2-1.3 μg/ml, which was almost as high as that of an AIDS drug, ddC, whose EC50=3.2 μg/ml, and moderate blood anticoagulant activity, AA=0.8-22.7 units/mg, compared to those of standard sulfated polysaccharides, curdlan (10 units/mg) and dextran (22.7 units/mg) sulfates. Structural analysis of sulfated konjac glucomannans with negatively charged sulfated groups was performed by high resolution NMR, and the interaction between poly-l-lysine with positively charged amino groups as a model compound of proteins and peptides was measured by surface plasmon resonance measurement, suggesting that the sulfated konjac glucomannans had a high binding stability on immobilized poly-l-lysine. The binding of sulfated konjac glucomannan was concentration-dependent, and the biological activity of the sulfated konjac glucomannans may be due to electrostatic interaction between the sulfate and amino groups.

  1. Modeling of ferric sulfate decomposition and sulfation of potassium chloride during grate‐firing of biomass

    DEFF Research Database (Denmark)

    Wu, Hao; Jespersen, Jacob Boll; Jappe Frandsen, Flemming

    2013-01-01

    Ferric sulfate is used as an additive in biomass combustion to convert the released potassium chloride to the less harmful potassium sulfate. The decomposition of ferric sulfate is studied in a fast heating rate thermogravimetric analyzer and a volumetric reaction model is proposed to describe...... the process. The yields of sulfur oxides from ferric sulfate decomposition under boiler conditions are investigated experimentally, revealing a distribution of approximately 40% SO3 and 60% SO2. The ferric sulfate decomposition model is combined with a detailed kinetic model of gas‐phase KCl sulfation...... and a model of K2SO4 condensation to simulate the sulfation of KCl by ferric sulfate addition. The simulation results show good agreements with experiments conducted in a biomass grate‐firing reactor. The results indicate that the SO3 released from ferric sulfate decomposition is the main contributor to KCl...

  2. Inhibition of synthesis of heparan sulfate by selenate: Possible dependence on sulfation for chain polymerization

    Energy Technology Data Exchange (ETDEWEB)

    Dietrich, C.P.; Nader, H.B. (Paulist School of Medicine, Sao Paulo (Brazil)); Buonassisi, V.; Colburn, P. (W. Alton Jones Cell Science Center, Lake Placid, NY (USA))

    1988-01-01

    Selenate, a sulfation inhibitor, blocks the synthesis of heparan sulfate and chondroitin sulfate by cultured endothelial cells. In contrast, selenate does not affect the production of hyaluronic acid, a nonsulfated glycosaminoglycan. No differences in molecular weight, ({sup 3}H)glucosamine/({sup 35}S)sulfuric acid ratios, or disaccharide composition were observed when the heparan sulfate synthesized by selenate-treated cells was compared with that of control cells. The absence of undersulfated chains in preparations from cultures exposed to selenate supports the concept that, in the intact cell, the polymerization of heparan sulfate might be dependent on the sulfation of the saccharide units added to the growing glycosaminoglycan chain.

  3. Evaluating Deterioration of Concrete by Sulfate Attack

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Effects of factors such as water to cement ratio, fly ash and silica fume on the resistance of concrete to sulfate attack were investigated by dry-wet cycles and immersion method. The index of the resistance to sulfate attack was used to evaluate the deterioration degree of concrete damaged by sulfate. The relationship between the resistance of concrete to sulfate attack and its permeability/porosity were analyzed as well as its responding mechanism. Results show that the depth of sulfate crystal attack from surface to inner of concrete can be reduced by decreasing w/c and addition of combining fly ash with silica fume. The variation of relative elastic modulus ratio and relative flexural strength ratio of various specimens before and after being subjected to sulfate attack was compared.

  4. Depolymerization of sulfated polysaccharides under hydrothermal conditions.

    Science.gov (United States)

    Morimoto, Minoru; Takatori, Masaki; Hayashi, Tetsuya; Mori, Daiki; Takashima, Osamu; Yoshida, Shinichi; Sato, Kimihiko; Kawamoto, Hitoshi; Tamura, Jun-ichi; Izawa, Hironori; Ifuku, Shinsuke; Saimoto, Hiroyuki

    2014-01-30

    Fucoidan and chondroitin sulfate, which are well known sulfated polysaccharides, were depolymerized under hydrothermal conditions (120-180°C, 5-60min) as a method for the preparation of sulfated polysaccharides with controlled molecular weights. Fucoidan was easily depolymerized, and the change of the molecular weight values depended on the reaction temperature and time. The degree of sulfation and IR spectra of the depolymerized fucoidan did not change compared with those of untreated fucoidan at reaction temperatures below 140°C. However, fucoidan was partially degraded during depolymerization above 160°C. Nearly the same depolymerization was observed for chondroitin sulfate. These results indicate that hydrothermal treatment is applicable for the depolymerization of sulfated polysaccharides, and that low molecular weight products without desulfation and deformation of the initial glycan structures can be obtained under mild hydrothermal conditions.

  5. Serum prolactin and dehydroepiandrosterone concentrations during the summer and winter hair growth cycles of mink (Mustela vison).

    Science.gov (United States)

    Rose, J; Kennedy, M; Johnston, B; Foster, W

    1998-11-01

    We investigated the relationship between serum concentrations of prolactin (PRL) and dehydroepiandrosterone (DHEA) during initiation and development of summer and winter hair growth (anagen) cycles in mink. In the spring, haloperidol (HAL) increased PRL concentrations and induced summer anagen earlier than controls, whereas melatonin (MEL) inhibited PRL secretion and completely blocked summer anagen. In the fall, HAL increased PRL concentrations, inducing anagen at an earlier time than controls, although the resulting fur was abnormal being almost devoid of underhair fibers. Exogenous MEL during the fall reduced PRL concentrations, initiating winter anagen 4 weeks earlier than controls. Adrenalectomy (ADX) induced earlier onset of summer and winter anagen and neutralized the inhibitory effects of HAL in the fall and MEL in the spring. No change in serum DHEA concentrations was observed during the onset of summer or winter anagen in any group although MEL increased DHEA levels from 27 March through 5 June relative to HAL-treated mink. We conclude that changes in serum levels of DHEA and PRL are not requisite to onset of summer or winter anagen in mink. It is possible that metabolites of DHEA and/or PRL may still affect other aspects of the hair growth cycle.

  6. Dehydroepiandrosterone activates AMP kinase and regulates GLUT4 and PGC-1α expression in C2C12 myotubes.

    Science.gov (United States)

    Yokokawa, Takumi; Sato, Koji; Iwanaka, Nobumasa; Honda, Hiroki; Higashida, Kazuhiko; Iemitsu, Motoyuki; Hayashi, Tatsuya; Hashimoto, Takeshi

    Exercise and caloric restriction (CR) have been reported to have anti-ageing, anti-obesity, and health-promoting effects. Both interventions increase the level of dehydroepiandrosterone (DHEA) in muscle and blood, suggesting that DHEA might partially mediate these effects. In addition, it is thought that either 5'-adenosine monophosphate-activated protein kinase (AMPK) or peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) mediates the beneficial effects of exercise and CR. However, the effects of DHEA on AMPK activity and PGC-1α expression remain unclear. Therefore, we explored whether DHEA in myotubes acts as an activator of AMPK and increases PGC-1α. DHEA exposure increased glucose uptake but not the phosphorylation levels of Akt and PKCζ/λ in C2C12 myotubes. In contrast, the phosphorylation levels of AMPK were elevated by DHEA exposure. Finally, we found that DHEA induced the expression of the genes PGC-1α and GLUT4. Our current results might reveal a previously unrecognized physiological role of DHEA; the activation of AMPK and the induction of PGC-1α by DHEA might mediate its anti-obesity and health-promoting effects in living organisms. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Effect of intravaginal dehydroepiandrosterone (DHEA) on the female sexual function in postmenopausal women: ERC-230 open-label study.

    Science.gov (United States)

    Bouchard, Céline; Labrie, Fernand; Derogatis, Leonard; Girard, Ginette; Ayotte, Normand; Gallagher, John; Cusan, Leonello; Archer, David F; Portman, David; Lavoie, Lyne; Beauregard, Adam; Côté, Isabelle; Martel, Céline; Vaillancourt, Mario; Balser, John; Moyneur, Erick

    2016-03-01

    Intravaginal DHEA (dehydroepiandrosterone, prasterone), the exclusive precursor of androgens and estrogens in postmenopausal women, has previously been shown to improve all the domains of sexual function by a strictly local action in the vagina. The well recognized female sexual function index (FSFI) questionnaire was used in the present study. The long-term effect of 52-week treatment with daily intravaginal 0.50% (6.5 mg) DHEA was evaluated on the various domains of female sexual function using the FSFI questionnaire at baseline, Week 26 and Week 52. One hundred and fifty-four postmenopausal women with at least one mild to severe symptom of vulvovaginal atrophy (VVA) and who have completed the FSFI questionnaire at baseline and at least one post-baseline timepoint were included in the analysis. The FSFI domains desire, arousal, lubrication, orgasm, satisfaction and pain were increased by 28%, 49%, 115%, 51%, 41% and 108%, respectively (pDHEA and all its metabolites, including estradiol and testosterone, show no meaningful change, the present clinical data indicate a stimulatory effect of intravaginal DHEA through a strictly local action in agreement with the preclinical data showing that the androgens made locally from DHEA in the vagina induce an increase in local nerve density.

  8. Influence of dehydroepiandrosterone on G-6-PD activity and /sup 3/H-thymidine uptake of human lymphocytes in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Ennas, M.G.; Laconi, S.; Dessi, S.; Milia, G.; Murru, M.R.; Manconi, P.E.

    1987-01-01

    Dehydroepiandrosterone (DHEA) was found to inhibit experimental cancer development in mouse and rat lung, colon and mammary gland. Since DHEA is a potent inhibitor of mammalian G-6-PD, the hypothesis that the compound could inhibit cell proliferation through an inhibition of the pentose phosphate pathway has been formulated. We studied the effects of DHEA on the proliferation in vitro of human lymphocytes induced by several mitogens (PHA, ConA and PWM), measuring /sup 3/H-thymidine uptake. DHEA inhibited /sup 3/H-thymidine uptake of mitogen-stimulated cells from both G-6-PD+ and G-6-PD- (mediterranean type deficiency) individuals in a dose-dependent and reversible fashion. The inhibitory effect was found even if DHEA was added to cells in the last hours of culture, simultaneously with the addition of /sup 3/H-thymidine. These data suggest that the inhibition of thymidine uptake induced by DHEA on human lymphocytes probably does not depend on the inhibition of G-6-PD.

  9. Increased serum levels of dehydroepiandrosterone (DHEA) and interleukin-6 (IL-6) in women with mild to moderate Alzheimer's disease.

    Science.gov (United States)

    Rasmuson, Sigbritt; Näsman, Birgitta; Olsson, Tommy

    2011-11-01

    It has been suggested that hypercortisolism contributes to the pathophysiology of Alzheimer's disease (AD), based on the fact that excess glucocorticoid exposure has potent adverse effects on the central nervous system. In contrast, dehydroepiandrosterone (DHEA) has been linked to a broad range of beneficial physiological effects including neuronal excitability and neuroprotection and even memory enhancing properties. Of note, proinflammatory cytokines are present in neuritic plaques (a hallmark of AD) and may regulate cortisol/DHEA release. In this exploratory study, we hypothesized that there is a flattened diurnal curve of cortisol and DHEA in mild to moderate AD, linked to increased cytokine levels. Diurnal profiles of cortisol, adrenocorticotropic hormone (ACTH), and DHEA were studied in 15 patients with mild to moderate AD (7 men and 8 women, 75.6 ± 5.5 years) and 15 healthy elderly controls (7 men and 8 women, 73.3 ± 5.8 years, respectively). Interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and soluble TNF receptors were analyzed. Women with AD had significantly increased morning levels of ACTH, DHEA, and IL-6 compared to healthy elderly women. Cortisol levels were significantly increased in men with AD at 0300 h versus healthy elderly men, in spite of slightly decreased ACTH levels. Our data suggest important sex differences in hypothalamic-pituitary-adrenal (HPA) axis regulation and steroid hormone clearance in patients with AD. Increased secretion of IL-6 may have a contributory role in this difference.

  10. Fecal dehydroepiandrosterone (DHEA) immunoreactivity as a noninvasive index of circulating DHEA activity in young male laboratory rats.

    Science.gov (United States)

    Bardi, Massimo; Hampton, Joseph E; Lambert, Kelly G

    2010-12-01

    Evidence suggests that dehydroepiandrosterone (DHEA) plays a key role in stress and coping responses. Fecal sampling permits assessment of hormone-behavior interactions reliably and effectively, but no previous study has compared circadian- or stress-dependent alterations between serum DHEA and its fecal metabolites. In the current study, young (28 d of age) male rats were assigned to either an experimental (n = 6) or control (n = 6) group. Rats in the experimental group were exposed to a forced swim test to assess their behavioral and physiologic response to an environmental stressor; blood samples were drawn before the test (baseline), immediately after the test, and at 2 later time points. Only fecal samples were collected from control animals. Fecal DHEA and corticosterone metabolites were monitored in all animals for 24 h. DHEA metabolites in control rats exhibited significant diurnal variation, showing a similar temporal pattern as that of corticosterone metabolites. In addition, fecal and serum DHEA levels were highly correlated. Significant peaks in both DHEA and corticosterone metabolite levels were detected. These data suggest that measures of fecal DHEA can provide a complementary, noninvasive method of assessing adrenal gland function in rats.

  11. The effort-reward imbalance work-stress model and daytime salivary cortisol and dehydroepiandrosterone (DHEA) among Japanese women.

    Science.gov (United States)

    Ota, Atsuhiko; Mase, Junji; Howteerakul, Nopporn; Rajatanun, Thitipat; Suwannapong, Nawarat; Yatsuya, Hiroshi; Ono, Yuichiro

    2014-09-17

    We examined the influence of work-related effort-reward imbalance and overcommitment to work (OC), as derived from Siegrist's Effort-Reward Imbalance (ERI) model, on the hypothalamic-pituitary-adrenocortical (HPA) axis. We hypothesized that, among healthy workers, both cortisol and dehydroepiandrosterone (DHEA) secretion would be increased by effort-reward imbalance and OC and, as a result, cortisol-to-DHEA ratio (C/D ratio) would not differ by effort-reward imbalance or OC. The subjects were 115 healthy female nursery school teachers. Salivary cortisol, DHEA, and C/D ratio were used as indexes of HPA activity. Mixed-model analyses of variance revealed that neither the interaction between the ERI model indicators (i.e., effort, reward, effort-to-reward ratio, and OC) and the series of measurement times (9:00, 12:00, and 15:00) nor the main effect of the ERI model indicators was significant for daytime salivary cortisol, DHEA, or C/D ratio. Multiple linear regression analyses indicated that none of the ERI model indicators was significantly associated with area under the curve of daytime salivary cortisol, DHEA, or C/D ratio. We found that effort, reward, effort-reward imbalance, and OC had little influence on daytime variation patterns, levels, or amounts of salivary HPA-axis-related hormones. Thus, our hypotheses were not supported.

  12. Comparison of 7 Published LC-MS/MS Methods for the Simultaneous Measurement of Testosterone, Androstenedione, and Dehydroepiandrosterone in Serum

    DEFF Research Database (Denmark)

    Büttler, Rahel M; Martens, Frans; Fanelli, Flaminia

    2015-01-01

    , and dehydroepiandrosterone (DHEA). METHODS: We used 7 published LC-MS/MS methods to analyze in duplicate 55 random samples from both men and women. We performed Passing-Bablok regression analysis and calculated Pearson correlation coefficients to assess the agreement of the methods investigated with the median concentration...... measured by all methods, and we calculated the intraassay CV of each method derived from duplicate results and the CVs between the methods. RESULTS: Median concentrations of testosterone were 0.22-1.36 nmol/L for women and 8.27-27.98 nmol/L for men. Androstenedione and DHEA concentrations were 0.......05-5.53 and 0.58-18.04 nmol/L, respectively. Intraassay CVs were 2.9%-10%, 1.2%-8.8%, 2.7%-13%, and 4.3%-16% for testosterone in women, testosterone in men, androstenedione, and DHEA. Slopes of the regression lines calculated by Passing-Bablok regression analysis were 0.92-1.08, 0.92-1.08, 0.90-1.13, and 0...

  13. Evidence that androgenic and estrogenic metabolites contribute to the effects of dehydroepiandrosterone on cognition in postmenopausal women.

    Science.gov (United States)

    Hirshman, Elliot; Merritt, Paul; Wang, Cecilia C L; Wierman, Margaret; Budescu, David V; Kohrt, Wendy; Templin, Jonathan L; Bhasin, Shalender

    2004-02-01

    Prior studies of the effects of dehydroepiandrosterone (DHEA) on cognition have produced complex and inconsistent results. We hypothesize that these results may arise, in part, because of DHEA's metabolism into estrogens and androgens that produce opposing effects on cognition. Our study administered 50 mg of oral DHEA daily for 4 weeks in a placebo-controlled crossover design to six postmenopausal women. We measured blood levels of androgens (total testosterone, free testosterone, DHEA, DHEAS), estrogens (estradiol, estrone), and cognitive performance on recognition memory, perceptual identification, digit span memory, and visual attentional vigilance under both drug and placebo conditions. Multiple regression models incorporating the factors of age and body mass index (BMI) were used to ascertain the relation between sex steroids and cognitive performance. Our results demonstrated that estrogens produced a positive effect on recognition memory, while androgens produced a negative effect. This pattern reversed in perceptual identification with estrogens producing a negative effect and androgens producing a positive effect. In addition, BMI produced a negative effect on digit span memory, age produced a negative effect on perceptual identification, and androgens produced a negative effect on visual attentional vigilance. These results help, in part, to explain DHEA's complex effects on cognition. The diverse effects of sex steroids across tasks underscore the importance of identifying the specific cognitive mechanisms influenced by sex steroids and emphasizes that one should not expect sex steroids to produce homogeneous effects across cognitive tasks.

  14. Dehydroepiandrosterone formation is independent of cytochrome P450 17alpha-hydroxylase/17, 20 lyase activity in the mouse brain.

    Science.gov (United States)

    Liu, Ying; Pocivavsek, Ana; Papadopoulos, Vassilios

    2009-07-01

    Cytochrome P450 17alpha-hydroxylase/17, 20 lyase (CYP17) is a microsomal enzyme reported to have two distinct catalytic activities, 17alpha-hydroxylase and 17, 20 lyase, that are essential for the biosynthesis of peripheral androgens such as dehydroepiandrosterone (DHEA). Paradoxically, DHEA is present and plays a role in learning and memory in the adult rodent brain, while CYP17 activity and protein are undetectable. To determine if CYP17 is required for DHEA formation and function in the adult rodent brain, we generated CYP17 chimeric mice that had reduced circulating testosterone levels. There were no detectable differences in cognitive spatial learning between CYP17 chimeric and wild-type mice. In addition, while CYP17 mRNA levels were reduced in CYP17 chimeric compared to wild-type mouse brain, the levels of brain DHEA levels were comparable. To determine if adult brain DHEA is formed by an alternative Fe(2+)-dependent pathway, brain microsomes were isolated from wild-type and CYP17 chimeric mice and treated with FeSO(4). Fe(2+) caused comparable levels of DHEA production by both wild-type and CYP17 chimeric mouse brain microsomes; DHEA production was not reduced by a CYP17 inhibitor. Taken together these in vivo studies suggest that in the adult mouse brain DHEA is formed via a Fe(2+)-sensitive CYP17-independent pathway.

  15. Treatment with dehydroepiandrosterone increases peripheral benzodiazepine receptors of mitochondria from cerebral cortex in D-galactose-induced aged rats.

    Science.gov (United States)

    Chen, Chunfu; Lang, Senyang; Zuo, Pingping; Yang, Nan; Wang, Xiangqing

    2008-12-01

    The aim of this study was to determine whether dehydroepiandrosterone (DHEA) could regulate the expression of peripheral benzodiazepine receptors of mitochondria in cerebral cortex. The rats were divided into five groups. Those, in the vehicle-physiological or senescent group, received physiological or d-galactose (subcutaneously) once a day. Rats, in the vehicle-dimethyl sulfoxide- or DHEA-treated senescent group, received 2% of dimethyl sulfoxide or DHEA (intraperitoneally) every other day besides D-galactose (subcutaneously) once a day. Rats in the DHEA-treated normal group received physiological once a day and DHEA every other day. After 8-week, spatial learning was assessed for 5 days by water maze methods. Following behavioural testing, the cerebral cortex mitochondria were purified for PK11195 binding analysis. When compared to the respective vehicle, D-galactose alone induced a significant impairment in water maze performance accompanied by a reduction (30.7%) in peripheral benzodiazepine receptor density of mitochondria, and DHEA displayed a significant enhancement in learning memory accompanied by the elevation (18.3%) of peripheral benzodiazepine receptor density but not affinity in senescent rats. DHEA showed insignificant effects on both learning/memory ability and peripheral benzodiazepine receptors in normal rats when compared to physiological saline. These results suggest that chronic treatment with DHEA enhance cognitive function and increase peripheral benzodiazepine receptor density in cerebral cortex mitochondria in middle-aged senescent rats.

  16. Simultaneous determination of pregnenolone sulphate, dehydroepiandrosterone and allopregnanolone in rat brain areas by liquid chromatography-electrospray tandem mass spectrometry.

    Science.gov (United States)

    Rustichelli, Cecilia; Pinetti, Diego; Lucchi, Chiara; Ravazzini, Federica; Puia, Giulia

    2013-07-01

    Neurosteroids (NSs) are well known modulators of neuronal activity and by binding to different neuronal receptors are responsible for a broad spectrum of biological and pathophysiological conditions. Here, a sensitive liquid chromatographic-electrospray ionization-tandem mass spectrometric method (LC-ESI-MS/MS) has been developed and validated for the simultaneous determination in rat brain areas of three NSs, i.e. pregnenolone sulphate (PS), dehydroepiandrosterone (DHEA) and allopregnanolone (AP). NSs were extracted with methanol-formic acid, purified by Hybrid-SPE cartridges and subjected to LC-ESI-MS/MS without any preliminary derivatization or deconjugation procedure. Quantitation was performed by multiple reaction monitoring mode with the internal standard method, using deuterium-labelled analogues of the analyzed NSs. The proposed method provided for the first time a direct quantitative determination of PS without hydrolysis; in particular, PS concentrations were found significantly (pmemory, than in cortical tissue of control rats, suggesting the important role of this NS in the process of memory formation. The developed method could be successfully applied to quantify simultaneously PS, DHEA and AP levels in brain tissue in order to study their changes during various neurodegenerative diseases and to investigate the role of PS in the brain. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. Effects of ning shen ling granule and dehydroepiandrosterone on cognitive function in mice undergoing chronic mild stress.

    Science.gov (United States)

    Zhang, Xiao; Dong, Yi-long; Yang, Nan; Liu, Yan-yong; Gao, Rui-feng; Zuo, Ping-ping

    2007-03-01

    To investigate the changes of spontaneous and cognitive behavior, and cholinergic M receptors in the brain of mice subjected to chronic mild stress (CMS), and to determine the effect of Ning Shen Ling Granule (NSL) and dehydroepiandrosterone (DHEA) on them. CMS model mice were established by applying stress every day for 3 consecutive weeks with 7 kinds of unforeseeable stress sources, and they were medicated for 1 week beginning at the 3rd week of modeling. The changes in behavior were determined by Morris Water Maze and spontaneous movement test, and M-receptor binding activity in cerebral cortex, hippocampus and hypothalamus were measured by radioactive ligand assay with 3H-QNB. (1) The spontaneous movement in CMS model mice was significantly reduced, with the latency for searching platform in Morris Water Maze obviously prolonged (PDHEA. (2) The binding ability of M-receptor in cerebral cortex and hippocampus of CMS mice was significantly decreased as compared with those in the control group (PDHEA. The decline of spontaneous movement and spatial learning and memory ability could be induced in animals by chronic mild stress, and that may be related to the low activity of central cholinergic M-receptors. Both NSL and DHEA could effectively alleviate the above-mentioned changes.

  18. Effect of dehydroepiandrosterone derivatives on the activity of 5α-reductase isoenzymes and on cancer cell line PC-3.

    Science.gov (United States)

    Bratoeff, Eugene; Garrido, Mariana; Ramírez-Apan, Teresa; Heuze, Yvonne; Sánchez, Araceli; Soriano, Juan; Cabeza, Marisa

    2014-11-01

    It is well known that testosterone (T) under the influence of 5α-reductase enzyme is converted to dihydrotestosterone (DHT), which causes androgen-dependent diseases. The aim of this study was to synthesize new dehydroepiandrosterone derivatives (3a-e, 4a-i, 6 and 7) having potential inhibitory activity against the 5α-reductase enzyme. This paper also reports the in vivo pharmacological effect of these steroidal molecules. The results from this study showed that all compounds exhibited low inhibitory activity for 5α-reductase type 1 and 2 enzymes and they failed to bind to the androgen receptor. Furthermore, in the in vivo experiment, steroids 3b, 4f, and 4 g showed comparable antiandrogenic activity to that of finasteride; only derivatives 4d and 7 produced a considerable decrease in the weight of the prostate gland of gonadectomized hamsters treated with (T). On the other hand, compounds 4a, f and h showed 100% inhibition of the growth of prostate cancer cell line PC-3, with compound 4 g having a 98.2% antiproliferative effect at 50 μM. The overall data indicated that these steroidal molecules, having an aromatic ester moiety at C-3 (4f-h), could have anticancer properties.

  19. Correlation of brain levels of progesterone and dehydroepiandrosterone with neurological recovery after traumatic brain injury in female mice.

    Science.gov (United States)

    Lopez-Rodriguez, Ana Belen; Acaz-Fonseca, Estefania; Giatti, Silvia; Caruso, Donatella; Viveros, Maria-Paz; Melcangi, Roberto C; Garcia-Segura, Luis M

    2015-06-01

    Traumatic brain injury (TBI) is an important cause of disability in humans. Neuroactive steroids, such as progesterone and dehydroepiandrosterone (DHEA), are neuroprotective in TBI models. However in order to design potential neuroprotective strategies based on neuroactive steroids it is important to determine whether its brain levels are altered by TBI. In this study we have used a weight-drop model of TBI in young adult female mice to determine the levels of neuroactive steroids in the brain and plasma at 24h, 72 h and 2 weeks after injury. We have also analyzed whether the levels of neuroactive steroids after TBI correlated with the neurological score of the animals. TBI caused neurological deficit detectable at 24 and 72 h, which recovered by 2 weeks after injury. Brain levels of progesterone, tetrahydroprogesterone (THP), isopregnanolone and 17β-estradiol were decreased 24h, 72 h and 2 weeks after TBI. DHEA and brain testosterone levels presented a transient decrease at 24h after lesion. Brain levels of progesterone and DHEA showed a positive correlation with neurological recovery. Plasma analyses showed that progesterone was decreased 72 h after lesion but, in contrast with brain progesterone, its levels did not correlate with neurological deficit. These findings indicate that TBI alters the levels of neuroactive steroids in the brain with independence of its plasma levels and suggest that the pharmacological increase in the brain of the levels of progesterone and DHEA may result in the improvement of neurological recovery after TBI.

  20. Development of a method for the measurement of dehydroepiandrosterone sulphate by liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Chadwick, C A; Owen, L J; Keevil, B G

    2005-11-01

    Dehydroepiandrosterone sulphate (DHEAS) is a steroid that is increasingly being recognized as a potential drug of abuse in many countries. This is due to its reputation as a hormone that may be able to retard the ageing process. The measurement of DHEAS is useful in the diagnosis of medical conditions such as congenital adrenal hyperplasia and polycystic ovary syndrome. Thus, a liquid chromatography-tandem mass spectrometry method has been developed to determine DHEAS concentrations in human serum. The chromatography was performed using a Waters 2795 Alliance HT LC system coupled to a Mercury Fusion-RP column fitted with a SecurityGuard column. DHEAS and the internal standard, deuterated DHEAS, both had a retention time of 1.5 min. The transition determined by the Micromass Quattro tandem mass spectrometer for DHEAS was m/z 367.3>4 96.7 and for the internal standard m/z 369.3>96.6. The method was linear up to 20 micromol/L; the lower limit of detection and the lower limit of quantitation were both 1 micromol/L. The intra- and interassay imprecision were Rad Lyphocheck QC. The measurement of DHEAS by liquid chromatography-tandem mass spectrometry is robust and has a simple sample preparation procedure with a rapid cycle time of only 4 min.

  1. Fat-reducing effects of dehydroepiandrosterone involve upregulation of ATGL and HSL expression, and stimulation of lipolysis in adipose tissue.

    Science.gov (United States)

    Karbowska, Joanna; Kochan, Zdzislaw

    2012-11-01

    Dehydroepiandrosterone (DHEA) reduces body fat in rodents and humans, and increases glycerol release from isolated rat epididymal adipocytes and human visceral adipose tissue explants. It suggests that DHEA stimulates triglyceride hydrolysis in adipose tissue; however, the mechanisms underlying this action are still unclear. We examined the effects of DHEA on the expression of adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL), the key enzymes of lipolysis, in rat epididymal white adipose tissue (eWAT). Male Wistar rats were fed a diet containing 0.6% DHEA for 2 weeks and eWAT was analyzed for mRNA and protein expression of ATGL and HSL, as well as mRNA expression of peroxisome proliferator-activated receptor γ 2 (PPARγ2) and its downstream target fatty acid translocase (FAT). Glycerol release from eWAT explants and serum free fatty acids (FFA) were also measured. Rats that received DHEA gained less weight, had 23% lower eWAT mass and 31% higher serum FFA levels than controls. Cultured explants of eWAT from DHEA-treated rats released 81% more glycerol than those from control rats. DHEA administration upregulated ATGL mRNA (1.62-fold, Padipose tissue by increasing the expression and activity of ATGL and HSL. The effects of DHEA appear to be mediated, at least in part, via PPARγ2 activation, which in turn upregulates ATGL and HSL gene expression. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. Effect of dehydroepiandrosterone on insulin action and development of insulin-induced resistance in C2C12 muscle cells

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    Dehydroepiandrosterone (DHEA), a precursor of androgens and estrogens, has been demonstrated to have effect of preventing insulin resistance and development of diabetes mellitus. Administration of testosterone appears to induce a marked insulin resistance. How these two hormones affect insulin resistance through regulation of sensitivity of tissues to insulin deserves further studies. Here, the effects of DHEA and testosterone on response to insulin in C2C12 muscle cells are analyzed. After 24 h of DHEA (10-6 mol/L) treatment, C2C12 cells showed an increased insulin- stimulated glucose uptake and enhanced activities of glycogen synthase (GS), phosphofructokinase (PFK) and pyruvate dehydrogenase (PDH), whereas testosterone gave the opposite effects. Incubation of C2C12 cells with high-dose insulin (5×10-7 mol/L) for 24 hours decreased their sensitivity to insulin and led to a state of resistance as assessed on insulin-stimulated glucose uptake and activities of GS, PFK and PDH. Addition of DHEA to insulin-resistant C2C12 cells could reverse the response of these cells to high-dose insulin, but testosterone could further impair insulin sensitivity in insulin-resistant C2C12 cells. These results suggest that the two hormones may influence the development or inhibition of insulin-resistance in type 2 diabetes through regulating glucose uptake, glycogenesis and glycolysis to some extent.

  3. Biological activity of pyrazole and imidazole-dehydroepiandrosterone derivatives on the activity of 17β-hydroxysteroid dehydrogenase.

    Science.gov (United States)

    Cabeza, Marisa; Posada, Alejandro; Sánchez-Márquez, Araceli; Heuze, Yvonne; Moreno, Isabel; Soriano, Juan; Garrido, Mariana; Cortés, Francisco; Bratoeff, Eugene

    2016-01-01

    The enzyme type 5 17β-hydroxysteroid dehydrogenase 5 (17β-HSD5) catalyzes the transformation of androstenedione (4-dione) to testosterone (T) in the prostate. This metabolic pathway remains active in cancer patients receiving androgen deprivation therapy. Since physicians seek to develop advantageous and better new treatments to increase the average survival of these patients, we synthesized several different dehydroepiandrosterone derivatives. These compounds have a pyrazole or imidazole function at C-17 and an ester moiety at C-3 and were studied as inhibitors of 17β-HSD5. The kinetic parameters of this enzyme were determined for use in inhibition assays. Their pharmacological effect was also determined on gonadectomized hamsters treated with Δ(4)-androstenedione (4-dione) or testosterone (T) and/or the novel compounds. The results indicated that the incorporation of a heterocycle at C-17 induced strong 17β-HSD5 inhibition. These derivatives decreased flank organ diameter and prostate weight in castrated hamsters treated with T or 4-dione. Inhibition of 17β-HSD5 by these compounds could have therapeutic potential for the treatment of prostate cancer and benign prostatic hyperplasia.

  4. DHEA supplementation in ovariectomized rats reduces impaired glucose-stimulated insulin secretion induced by a high-fat diet

    Directory of Open Access Journals (Sweden)

    Katherine Veras

    2014-01-01

    Full Text Available Dehydroepiandrosterone (DHEA and the dehydroepiandrosterone sulfate (DHEA-S are steroids produced mainly by the adrenal cortex. There is evidence from both human and animal models suggesting beneficial effects of these steroids for obesity, diabetes mellitus, hypertension, and osteoporosis, conditions associated with the post-menopausal period. Accordingly, we hypothesized that DHEA supplementation in ovariectomized (OVX female rats fed a high-fat diet would maintain glucose-induced insulin secretion (GSIS and pancreatic islet function. OVX resulted in a 30% enlargement of the pancreatic islets area compared to the control rats, which was accompanied by a 50% reduction in the phosphorylation of AKT protein in the pancreatic islets. However, a short-term high-fat diet induced insulin resistance, accompanied by impaired GSIS in isolated pancreatic islets. These effects were reversed by DHEA treatment, with improved insulin sensitivity to levels similar to the control group, and with increased serine phosphorylation of the AKT protein. These data confirm the protective effect of DHEA on the endocrine pancreas in a situation of diet-induced overweight and low estrogen concentrations, a phenotype similar to that of the post-menopausal period.

  5. Significant role of organic sulfur in supporting sedimentary sulfate reduction in low-sulfate environments

    Science.gov (United States)

    Fakhraee, Mojtaba; Li, Jiying; Katsev, Sergei

    2017-09-01

    Dissimilatory sulfate reduction (DSR) is a major carbon mineralization pathway in aquatic sediments, soils, and groundwater, which regulates the production of hydrogen sulfide and the mobilization rates of biologically important elements such as phosphorus and mercury. It has been widely assumed that water-column sulfate is the main sulfur source to fuel this reaction in sediments. While this assumption may be justified in high-sulfate environments such as modern seawater, we argue that in low-sulfate environments mineralization of organic sulfur compounds can be an important source of sulfate. Using a reaction-transport model, we investigate the production of sulfate from sulfur-containing organic matter for a range of environments. The results show that in low sulfate environments (50%) of sulfate reduction. In well-oxygenated systems, porewater sulfate profiles often exhibit sub-interface peaks so that sulfate fluxes are directed out of the sediment. Our measurements in Lake Superior, the world's largest lake, corroborate this conclusion: offshore sediments act as sources rather than sinks of sulfate for the water column, and sediment DSR is supported entirely by the in-sediment production of sulfate. Sulfate reduction rates are correlated to the depth of oxygen penetration and strongly regulated by the supply of reactive organic matter; rate co-regulation by sulfate availability becomes appreciable below 500 μM level. The results indicate the need to consider the mineralization of organic sulfur in the biogeochemical cycling in low-sulfate environments, including several of the world's largest freshwater bodies, deep subsurface, and possibly the sulfate-poor oceans of the Early Earth.

  6. Discovery of a Heparan sulfate 3- o -sulfation specific peeling reaction

    NARCIS (Netherlands)

    Huang, Yu; Mao, Yang; Zong, Chengli; Lin, Cheng; Boons, Geert Jan; Zaia, Joseph

    2015-01-01

    Heparan sulfate (HS) 3-O-sulfation determines the binding specificity of HS/heparin for antithrombin III and plays a key role in herpes simplex virus (HSV) infection. However, the low natural abundance of HS 3-O-sulfation poses a serious challenge for functional studies other than the two cases ment

  7. Involvement of highly sulfated chondroitin sulfate in the metastasis of the Lewis lung carcinoma cells.

    NARCIS (Netherlands)

    Li, F.; Dam, G.B. ten; Murugan, S.; Yamada, S.; Hashiguchi, T.; Mizumoto, S.; Oguri, K.; Okayama, M.; Kuppevelt, A.H.M.S.M. van; Sugahara, K.

    2008-01-01

    The altered expression of cell surface chondroitin sulfate (CS) and dermatan sulfate (DS) in cancer cells has been demonstrated to play a key role in malignant transformation and tumor metastasis. However, the functional highly sulfated structures in CS/DS chains and their involvement in the process

  8. Fucoidans - sulfated polysaccharides of brown algae

    Energy Technology Data Exchange (ETDEWEB)

    Usov, Anatolii I; Bilan, M I [N.D.Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow (Russian Federation)

    2009-08-31

    The methods of isolation of fucoidans and determination of their chemical structures are reviewed. The fucoidans represent sulfated polysaccharides of brown algae, the composition of which varies from simple fucan sulfates to complex heteropolysaccharides. The currently known structures of such biopolymers are presented. A variety of the biological activities of fucoidans is briefly summarised.

  9. Fucoidans — sulfated polysaccharides of brown algae

    Science.gov (United States)

    Usov, Anatolii I.; Bilan, M. I.

    2009-08-01

    The methods of isolation of fucoidans and determination of their chemical structures are reviewed. The fucoidans represent sulfated polysaccharides of brown algae, the composition of which varies from simple fucan sulfates to complex heteropolysaccharides. The currently known structures of such biopolymers are presented. A variety of the biological activities of fucoidans is briefly summarised.

  10. Primary mesenchyme cell migration requires a chondroitin sulfate/dermatan sulfate proteoglycan.

    Science.gov (United States)

    Lane, M C; Solursh, M

    1991-02-01

    Primary mesenchyme cell migration in the sea urchin embryo is inhibited by sulfate deprivation and exposure to exogenous beta-D-xylosides, two treatments known to disrupt proteoglycan synthesis. We show that in the developing sea urchin, exogenous xyloside affects the synthesis by the primary mesenchyme cells of a very large, cell surface chondroitin sulfate/dermatan sulfate proteoglycan. This proteoglycan is present in a partially purified fraction that restores migratory ability to defective cells in vitro. The integrity of this chondroitin sulfate/dermatan sulfate proteoglycan appears essential for primary mesenchyme cell migration since treatment of actively migrating cells with chondroitinase ABC reversibly inhibited their migration in vitro.

  11. Metabolic Flexibility of Sulfate Reducing Bacteria

    Directory of Open Access Journals (Sweden)

    Caroline M. Plugge

    2011-05-01

    Full Text Available Dissimilatory sulfate-reducing prokaryotes (SRB are a very diverse group of anaerobic bacteria that are omnipresent in nature and play an imperative role in the global cycling of carbon and sulfur. In anoxic marine sediments sulfate reduction accounts for up to 50% of the entire organic mineralization in coastal and shelf ecosystems where sulfate diffuses several meters deep into the sediment. As a consequence, SRB would be expected in the sulfate-containing upper sediment layers, whereas methanogenic Archaea would be expected to succeed in the deeper sulfate-depleted layers of the sediment. Where sediments are high in organic matter, sulfate is depleted at shallow sediment depths, and biogenic methane production will occur. In the absence of sulfate, many SRB ferment organic acids and alcohols, producing hydrogen, acetate, and carbon dioxide, and may even rely on hydrogen- and acetate-scavenging methanogens to convert organic compounds to methane. SRB can establish two different life styles, and these can be termed as sulfidogenic and acetogenic, hydrogenogenic metabolism. The advantage of having different metabolic capabilities is that it raises the chance of survival in environments when electron acceptors become depleted. In marine sediments, SRB and methanogens do not compete but rather complement each other in the degradation of organic matter.Also in freshwater ecosystems with sulfate concentrations of only 10-200 μM, sulfate is consumed efficiently within the top several cm of the sediments. Here, many of the δ-Proteobacteria present have the genetic machinery to perform dissimilatory sulfate reduction, yet they have an acetogenic, hydrogenogenic way of life.In this review we evaluate the physiology and metabolic mode of SRB in relation with their environment.

  12. Dehydroepiandrosterone (DHEA) is an anabolic steroid like dihydrotestosterone (DHT), the most potent natural androgen, and tetrahydrogestrinone (THG).

    Science.gov (United States)

    Labrie, Fernand; Luu-The, Van; Martel, Céline; Chernomoretz, Ariel; Calvo, Ezequiel; Morissette, Jean; Labrie, Claude

    2006-07-01

    We have recently taken advantage of the unique power of DNA microarrays to compare the genomic expression profile of tetrahydrogestrinone (THG) with that of dihydrotestosterone (DHT), the most potent natural androgen, thus clearly demonstrating that THG is an anabolic steroid. In 2004, the U.S. Controlled Substances Act has been modified to include androstenedione (4-dione) as an anabolic steroid. However, despite the common knowledge that dehydroepiandrosterone (DHEA) is the precursor of testosterone, DHEA has been excluded from the list of anabolic steroids. We thus used the same DNA microarray technology to analyze the expression profile of practically all the 30,000 genes of the mouse genome modulated by DHEA and DHT in classical androgen-sensitive tissues. Daily subcutaneous injections of DHT (0.1mg) or DHEA (3mg) for 1 month in gonadectomized C57BL6/129 SV mice increased ventral prostate, dorsal prostate, seminal vesicle and preputial gland weight (p or =30%), in the prostate (ventral+dorsal), seminal vesicles and preputial glands, respectively, compared to tissues from gonadectomized control animals. After 7 days of daily treatment with DHEA and DHT, 629, 919 and 562 probe sets were commonly modulated in the same tissues while after 27 days of treatment, 1195, 5127 and 2883 probe sets were modulated, respectively. In analogy with the data obtained with THG, the present microarray data provide an extremely precise and unquestionable genomic signature and proof of the androgenic/anabolic activity of DHEA. Such data add to the literature showing that DHEA is transformed into androgens in the human peripheral tissues as well as in laboratory animal species, including the monkey, thus exerting potent androgenic/anabolic activity. The present microarray approach to identify anabolic compounds is applicable to all potential androgenic/anabolic compounds.

  13. Ample Evidence: Dehydroepiandrosterone (DHEA Conversion into Activated Steroid Hormones Occurs in Adrenal and Ovary in Female Rat.

    Directory of Open Access Journals (Sweden)

    Yingqiao Zhou

    Full Text Available Dehydroepiandrosterone (DHEA is important for human health, especially for women. All estrogens and practically half of androgens are synthesized from DHEA in peripheral tissues. However, the mechanism and exact target tissues of DHEA biotransformation in the female are not fully clear. The present study showed that maximal content of androstenedione (AD and testosterone (T were observed at 3h after DHEA administration in female rats, which was 264% and 8000% above the control, respectively. Estradiol (E2 content significantly increased at 6h after DHEA administration, which was 113% higher than that in control group. Gavage with DHEA could significantly reduce 3β-hydroxysteroid dehydrogenase (3β-HSD mRNA level at 3-12h and 17β-hydroxysteroid dehydrogenase (17β-HSD mRNA level at 12h in ovary, while increasing aromatase mRNA levels at 6, 24, and 48 h. It is interesting that administration of DHEA caused a significant increase of 17β-HSD, 3β-HSD and aromatase mRNA levels in adrenal. The AD and T contents also markedly increased by 537% and 2737% after DHEA administration in ovariectomised rats, in company with a significant increase in 17β-HSD and 3β-HSD mRNA levels and decreased aromatase mRNA level in adrenal. However, DHEA administration did not restore the decreased E2, estrone (E1, and progesterone (P caused by the removal of the ovaries in females. These results clearly illustrated that exogenous DHEA is preferentially converted into androgens in adrenal, while its conversion to estrogens mainly happens in the ovary through steroidogenic enzyme in female rats.

  14. Effect of dehydroepiandrosterone (DHEA) on memory and brain derived neurotrophic factor (BDNF) in a rat model of vascular dementia.

    Science.gov (United States)

    Sakr, H F; Khalil, K I; Hussein, A M; Zaki, M S A; Eid, R A; Alkhateeb, M

    2014-02-01

    The effect of dehydroepiandrosterone (DHEA) on memory and cognition in experimental animals is well known, but its efficacy in clinical dementia is unproven. So, the aim of the present study was to investigate the effect of DHEA on learning and memory activities in a rat model of vascular dementia (VD). Forty-eight male rats that positively passed the holeboard memory test were chosen for the study before bilateral permanent occlusion of the common carotid artery. They were divided into four groups (n=12, each) as follows (i) untreated control, (ii) rats exposed to surgical permanent bilateral occlusion of the common carotid arteries (BCCAO) leading to chronic cerebral hypoperfusion, (iii) rats exposed to BCCAO then received DHEA (BCCAO + DHEA) and (i.v.) rats exposed to BCCAO then received donepezil (BCCAO + DON). Holeboard memory test was used to assess the time, latency, working memory and reference memory. Central level of acetylcholine, norepinephrine and dopamine in the hippocampus were measured. Furthermore, the expression of brain derived neurotrophic factor (BDNF) in the hippocampus was determined. Histopathological studies of the cerebral cortex and transmission electron microscope of the hippocampus were performed. BCCAO decreased the learning and memory activities in the holeboard memory. Also, it decreased the expression of BDNF as well as the central level of acetylcholine, noradrenaline and dopamine as compared to control rats. Treatment with DHEA and donepezil increased the working and reference memories, BDNF expression as well as the central acetylcholine in the hippocampus as compared to BCCAO rats. DHEA produced neuroprotective effects through increasing the expression of BDNF as well as increasing the central level of acetylcholine and catecholamines which are non-comparable to donepezil effects.

  15. The neurosteroid dehydroepiandrosterone (DHEA) protects the retina from AMPA-induced excitotoxicity: NGF TrkA receptor involvement.

    Science.gov (United States)

    Kokona, Despina; Charalampopoulos, Ioannis; Pediaditakis, Iosif; Gravanis, Achille; Thermos, Kyriaki

    2012-04-01

    The aim of the present study was to investigate the neuroprotective properties of the endogenous neurosteroid dehydroepiandrosterone (DHEA) in an in vivo model of retinal excitotoxicity, and the involvement of Nerve Growth Factor (NGF) in its actions. Adult Sprague-Dawley rats (250-300 g) received intravitreally (RS)-alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid hydrobromide (AMPA; 42 nmol/eye) alone or in combination with DHEA (10(-8), 10(-7), 10(-6) M), or PBS (50 mM, control group). To examine the involvement of NGF and its TrkA receptor in the pharmacological effects of DHEA, animals received AMPA and NGF (60 pg/eye) in the absence or presence of a TrkA receptor inhibitor (Calbiochem 648450, 10(-6) M) or AMPA, DHEA (10(-6) M) and TrkA receptor inhibitor (10(-6), 10(-5) M). Immunohistochemistry studies [choline acetyltransferase (ChAT), brain nitric oxide synthetase (bNOS), calbindin, and TUNEL] and fluorescence-activated cell sorting (FACS) were used to examine retinal cell loss and protection. TrkA receptor immunoreactivity (-IR) and colocalization studies with relevant markers were also performed. AMPA (42 nmol) treatment resulted in a loss of bNOS, ChAT and calbindin immunoreactivities 24 h after its administration. DHEA, administered intravitreally, protected the retina from excitotoxicity in a dose-dependent manner. This effect was mimicked by NGF, and reversed by the NGF TrkA receptor inhibitor. The TrkA receptor is expressed in ganglion cells of rat retina. TUNEL staining and FACS analysis substantiated the neuroprotective actions of DHEA. These results demonstrate for the first time that the neurosteroid DHEA, administered intravitreally, protects the retina from AMPA excitotoxicity. An NGF TrkA receptor mechanism appears to be involved in this neuroprotection. Copyright © 2012 Elsevier Ltd. All rights reserved.

  16. Ample Evidence: Dehydroepiandrosterone (DHEA) Conversion into Activated Steroid Hormones Occurs in Adrenal and Ovary in Female Rat.

    Science.gov (United States)

    Zhou, Yingqiao; Kang, Jian; Chen, Di; Han, Ningning; Ma, Haitian

    2015-01-01

    Dehydroepiandrosterone (DHEA) is important for human health, especially for women. All estrogens and practically half of androgens are synthesized from DHEA in peripheral tissues. However, the mechanism and exact target tissues of DHEA biotransformation in the female are not fully clear. The present study showed that maximal content of androstenedione (AD) and testosterone (T) were observed at 3h after DHEA administration in female rats, which was 264% and 8000% above the control, respectively. Estradiol (E2) content significantly increased at 6h after DHEA administration, which was 113% higher than that in control group. Gavage with DHEA could significantly reduce 3β-hydroxysteroid dehydrogenase (3β-HSD) mRNA level at 3-12h and 17β-hydroxysteroid dehydrogenase (17β-HSD) mRNA level at 12h in ovary, while increasing aromatase mRNA levels at 6, 24, and 48 h. It is interesting that administration of DHEA caused a significant increase of 17β-HSD, 3β-HSD and aromatase mRNA levels in adrenal. The AD and T contents also markedly increased by 537% and 2737% after DHEA administration in ovariectomised rats, in company with a significant increase in 17β-HSD and 3β-HSD mRNA levels and decreased aromatase mRNA level in adrenal. However, DHEA administration did not restore the decreased E2, estrone (E1), and progesterone (P) caused by the removal of the ovaries in females. These results clearly illustrated that exogenous DHEA is preferentially converted into androgens in adrenal, while its conversion to estrogens mainly happens in the ovary through steroidogenic enzyme in female rats.

  17. HIV-TB coinfection impairs CD8(+) T-cell differentiation and function while dehydroepiandrosterone improves cytotoxic antitubercular immune responses.

    Science.gov (United States)

    Suarez, Guadalupe V; Angerami, Matías T; Vecchione, María B; Laufer, Natalia; Turk, Gabriela; Ruiz, Maria J; Mesch, Viviana; Fabre, Bibiana; Maidana, Patricia; Ameri, Diego; Cahn, Pedro; Sued, Omar; Salomón, Horacio; Bottasso, Oscar A; Quiroga, María F

    2015-09-01

    Tuberculosis (TB) is the leading cause of death among HIV-positive patients. The decreasing frequencies of terminal effector (TTE ) CD8(+) T cells may increase reactivation risk in persons latently infected with Mycobacterium tuberculosis (Mtb). We have previously shown that dehydroepiandrosterone (DHEA) increases the protective antitubercular immune responses in HIV-TB patients. Here, we aimed to study Mtb-specific cytotoxicity, IFN-γ secretion, memory status of CD8(+) T cells, and their modulation by DHEA during HIV-TB coinfection. CD8(+) T cells from HIV-TB patients showed a more differentiated phenotype with diminished naïve and higher effector memory and TTE T-cell frequencies compared to healthy donors both in total and Mtb-specific CD8(+) T cells. Notably, CD8(+) T cells from HIV-TB patients displayed higher Terminal Effector (TTE ) CD45RA(dim) proportions with lower CD45RA expression levels, suggesting a not fully differentiated phenotype. Also, PD-1 expression levels on CD8(+) T cells from HIV-TB patients increased although restricted to the CD27(+) population. Interestingly, DHEA plasma levels positively correlated with TTE in CD8(+) T cells and in vitro DHEA treatment enhanced Mtb-specific cytotoxic responses and terminal differentiation in CD8(+) T cells from HIV-TB patients. Our data suggest that HIV-TB coinfection promotes a deficient CD8(+) T-cell differentiation, whereas DHEA may contribute to improving antitubercular immunity by enhancing CD8(+) T-cell functions during HIV-TB coinfection. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Beneficial effects of the sigma1 receptor agonists igmesine and dehydroepiandrosterone against learning impairments in rats prenatally exposed to cocaine.

    Science.gov (United States)

    Meunier, Johann; Maurice, Tangui

    2004-01-01

    In utero cocaine (IUC) exposure results in offspring rats in complex neurochemical and behavioral alterations, particularly affecting learning and memory processes. We examined here the impact of IUC exposure on memory functions in male and female offspring rats and report that selective sigma(1) (sigma(1)) receptor agonists are effective in reversing the deficits. Dams received a daily cocaine, 20 mg/kg ip, injection between gestational days E17 to E20. Learning was examined in offspring between day P30 and P41 using delayed alternation in the T-maze, water-maze learning and passive avoidance. Both male and female rats prenatally exposed to cocaine showed delayed alternation deficits and impairments of acquisition of a fixed platform position in the water maze, as shown by higher acquisition latencies and diminutions of time spent in the training quadrant during the probe test. The acquisition of a daily changing platform position also demonstrated impaired working memory. Finally, passive avoidance deficits were observed. Pretreatment with the synthetic sigma(1) agonist igmesine (0.1-1 mg/kg ip) or the neuroactive steroid dehydroepiandrosterone (DHEA 10-40 mg/kg ip) reversed the prenatal cocaine-induced learning deficits in offspring rats for each test. The sigma(1) antagonist BD1063 (1 mg/kg ip) failed to affect performances alone but blocked the igmesine and DHEA effects, confirming the involvement of the sigma(1) receptor. IUC exposure thus results in marked memory deficits, affecting spatial and nonspatial short- and long-term memories in juvenile male and female offspring rats. The activation of the sigma(1) neuromodulatory receptor allows a complete behavioral recovery of the memory functions in prenatally cocaine-exposed rats.

  19. Metabolism of dehydroepiandrosterone by rat hippocampal cells in culture: possible role of aromatization and 7-hydroxylation in neuroprotection.

    Science.gov (United States)

    Jellinck, P H; Lee, S J; McEwen, B S

    2001-10-01

    The rate of metabolism of the multifunctional neurosteroid, dehydroepiandrosterone (DHEA), by embryonic rat hippocampal cells maintained in culture was compared to that of 4-androstenedione (AD), the immediate precursor of estrone (E1). The experiments were carried out to assess the relative contribution of DHEA, its 7-hydroxylated metabolites and estrogen on their reported effects on memory and neuroprotection. The 3H-labeled steroids of high specific radioactivity were incubated for 1, 8, 24 and 48 h and the putative metabolites extracted from the culture medium with acetone-ethyl acetate before separation by TLC for radioassay. [3H]DHEA (2.0 ng/5x10(5) cells) yielded primarily the 7alpha- and 7beta-hydroxylated steroids in an almost equal ratio under conditions that resembled those used by others to study the protection of neurons by hippocampal astrocytes against excitatory amino acid-induced toxicity. The rate of conversion of DHEA to AD, and particularly to E1, was much lower. With [3H]AD as substrate, significant aromatization to estrogen occurred only after 24 h when most of [3H]DHEA had already been converted to its 7-hydroxylated products and the hydroxylase and aromatase systems would no longer be competing for the same coenzyme (NADPH). The hippocampal cells were still viable after 48 h of incubation with the steroids and were able to oxidize estradiol (E2) to E1 and reduce E1 to E2 and AD to testosterone (T). It is suggested that 7alpha- and 7beta-OHDHEA, the main metabolites formed in the rat hippocampus, might be responsible for some of the functions previously ascribed to estrogens in the brain and the reasons for this proposal are discussed.

  20. Faulty serotonin--DHEA interactions in autism: results of the 5-hydroxytryptophan challenge test.

    Science.gov (United States)

    Croonenberghs, Jan; Spaas, Kristien; Wauters, Annick; Verkerk, Robert; Scharpe, Simon; Deboutte, Dirk; Maes, Michael

    2008-06-01

    Autism is accompanied by peripheral and central disorders in the metabolism of serotonin (5-HT). The present study examines plasma dehydroepiandrosterone-sulphate (DHEA-S) and the cortisol/DHEA-S ratio following administration of L-5-hydroxytryptophan (5-HTP), the direct precursor of 5-HT, to autistic patients. Plasma DHEA-S levels were determined both before and after administration of 5-HTP or placebo, on two consecutive days in a single blind order in 18 male autistic patients and 22 matched healthy controls. The 5-HTP-induced DHEA-S responses were significantly higher in autistic patients than in controls. In baseline conditions, the cortisol/DHEA-S ratio was significantly higher in autistic patients than in controls. The results suggest that autism is accompanied by a major disequilibrium in the serotonergic system. The increased Cortisol (neurotoxic) versus DHEA-S (neuroprotective) ratio suggests that an increased neurotoxic potential occurs in autism. It is concluded that a disequilibrium in the peripheral and central turnover of serotonin and an increased neurotoxic capacity by glucocorticoids are important pathways in autism.

  1. Optimization of a biological sulfate reduction process

    Energy Technology Data Exchange (ETDEWEB)

    Lebel, A.

    1985-01-01

    A biological sulfate reduction process is presented. It is intended to treat sulfate wastes by converting them to hydrogen sulfide which can be further oxidized to elemental sulfur. An optimization study of a completely-mixed reactor system was performed. Major operating parameters were determined at the bench-scale level. The study was conducted in batch-culture experiments, using a mixed Desulfovibrio culture from sewage. Kinetic values were extrapolated using the Michaelis-Menten model, which best fitted the experimental data. The iron loading and the sulfate loading significantly affected the growth and metabolism of sulfate reducing bacteria (SRB). A model to determine V/sub m/ from the iron and sulfate loading values was explored. The model is limited by sulfate loading greater than 4.3 g/l, where bacterial growth is inhibited. Iron loading is not anticipated to suppress the bacterial metabolism efficiency since it remained in the linear pattern even at inhibition levels. Studies of the metabolic behavior of SRB, using lactic acid as the carbon source, showed a requirement of 2.7 moles of lactate for each mole of sulfate. This technique and its application to the sulfur recovery process are discussed.

  2. Using Terrestrial Sulfate Efflorescences as an Analogue of Hydrated Sulfate Formation in Valles Marineris on Mars

    Science.gov (United States)

    Smith, P. C.; Szynkiewicz, A.

    2015-12-01

    Hydrated sulfate minerals provide conclusive evidence that a hydrologic cycle was once active on the surface of Mars. Two classes of hydrated sulfate minerals have been detected by robotic instruments on Mars: monohydrated sulfate minerals comprised of kieserite and gypsum, and various polyhydrated sulfates with Fe-Ca-Na-Mg-rich compositions. These minerals are found in various locations on Mars, including large surface exposures in valley settings of Valles Marineris. However, the sulfate sources and formation mechanisms of these minerals are not yet well understood.Recently, it has been suggested that the sulfate minerals in Valles Marineris might have formed in a manner similar to sulfate efflorescences found in dry environments on Earth. In this study, we use sulfate effloresences from the Rio Puerco Watershed, New Mexico as a terrestrial analogue to assess major factors that might have led to deposition of sulfate minerals in Valles Marineris. In different seasons indicative of dry and wet conditions, we collected field photographs and sediment samples for chemical and stable isotopic analyses (sulfur content, δ34S) to determine major sources of sulfate ions for efflorescences and to assess how the seasonal changes in surface/groundwater activity affect their formation. Preliminary sulfur isotope results suggest that oxidation of bedrock sulfides (0.01-0.05 wt. S %) is a major source of sulfate ion for efflorescences formation because their δ34S varied in negative range (-28 to -20‰) similar to sulfides (average -32‰). Using field photographs collected in Oct 2006, Feb and Nov 2012, May 2013, Mar and Oct 2014, we infer that the highest surface accumulation of sulfate efflorescences in the studied analog site was observed after summer monsoon seasons when more water was available for surface and subsurface transport of solutes from chemical weathering. Conversely, spring snow melt led to enhanced dissolution of sulfate efflorescences.

  3. The role of sulfate in aerobic granular sludge process for emerging sulfate-laden wastewater treatment.

    Science.gov (United States)

    Xue, Weiqi; Hao, Tianwei; Mackey, Hamish R; Li, Xiling; Chan, Richard C; Chen, Guanghao

    2017-11-01

    Sulfate-rich wastewaters pose a major threat to mainstream wastewater treatment due to the unpreventable production of sulfide and associated shift in functional bacteria. Aerobic granular sludge could mitigate these challenges in view of its high tolerance and resilience against changes in various environmental conditions. This study aims to confirm the feasibility of aerobic granular sludge in the treatment of sulfate containing wastewater, investigate the impact of sulfate on nutrient removal and granulation, and reveal metabolic relationships in the above processes. Experiments were conducted using five sequencing batch reactors with different sulfate concentrations operated under alternating anoxic/aerobic condition. Results showed that effect of sulfate on chemical oxygen demand (COD) removal is negligible, while phosphate removal was enhanced from 12% to 87% with an increase in sulfate from 0 to 200 mg/L. However, a long acclimatization of the biomass (more than 70 days) is needed at a sulfate concentration of 500 mg/L and a total deterioration of phosphate removal at 1000 mg/L. Batch tests revealed that sulfide promoted volatile fatty acids (VFAs) uptake, producing more energy for phosphate uptake when sulfate concentrations were beneath 200 mg/L. However, sulfide detoxification became energy dominating, leaving insufficient energy for Polyhydroxyalkanoate (PHA) synthesis and phosphate uptake when sulfate content was further increased. Granulation accelerated with increasing sulfate levels by enhanced production of N-Acyl homoserine lactones (AHLs), a kind of quorum sensing (QS) auto-inducer, using S-Adenosyl Methionine (SAM) as primer. The current study demonstrates interactions among sulfate metabolism, nutrients removal and granulation, and confirms the feasibility of using the aerobic granular sludge process for sulfate-laden wastewaters treatment with low to medium sulfate content. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Di-sulfated Keratan Sulfate as a Novel Biomarker for Mucopolysaccharidosis II, IVA, and IVB.

    Science.gov (United States)

    Shimada, Tsutomu; Tomatsu, Shunji; Mason, Robert W; Yasuda, Eriko; Mackenzie, William G; Hossain, Jobayer; Shibata, Yuniko; Montaño, Adriana M; Kubaski, Francyne; Giugliani, Roberto; Yamaguchi, Seiji; Suzuki, Yasuyuki; Orii, Kenji E; Fukao, Toshiyuki; Orii, Tadao

    2015-01-01

    Keratan sulfate (KS) is a storage material in mucopolysaccharidosis IV (MPS IV). However, no detailed analysis has been reported on subclasses of KS: mono-sulfated KS and di-sulfated KS. We established a novel method to distinguish and quantify mono- and di-sulfated KS using liquid chromatography-tandem mass spectrometry and measured both KS levels in various specimens.Di-sulfated KS was dominant in shark cartilage and rat serum, while mono-sulfated KS was dominant in bovine cornea and human serum. Levels of both mono- and di-sulfated KS varied with age in the blood and urine from control subjects and patients with MPS II and IVA. The mean levels of both forms of KS in the plasma/serum from patients with MPS II, IVA, and IVB were elevated compared with that in age-matched controls. Di-sulfated KS provided more significant difference between MPS IVA and the age-matched controls than mono-sulfated KS. The ratio of di-sulfated KS to total KS in plasma/serum increased with age in control subjects and patients with MPS II but was age independent in MPS IVA patients. Consequently, this ratio can discriminate younger MPS IVA patients from controls. Levels of mono- and di-sulfated KS in urine of MPS IVA and IVB patients were all higher than age-matched controls for all ages studied.In conclusion, the level of di-sulfated KS and its ratio to total KS can distinguish control subjects from patients with MPS II, IVA, and IVB, indicating that di-sulfated KS may be a novel biomarker for these disorders.

  5. Analysis of tyrosine-O-sulfation

    DEFF Research Database (Denmark)

    Bundgaard, J.R.; Sen, J.W.; Johnsen, A.H.

    2008-01-01

    Tyrosine O-sulfation was first described about 50 years ago as a post-translational modification of fibrinogen. In the following 30 years it was considered to be a rare modification affecting only a few proteins and peptides. However, in the beginning of the 1980s tyrosine (Tyr) sulfation was shown...... the presence of radioactively labeled tyrosine. These techniques have been described in detail previously. The aim of this chapter is to present alternative analytical methods of Tyr sulfation than radioisotope incorporation before analysis Udgivelsesdato: 2008...

  6. Sulfated binary and trinary oxide solid superacids

    Institute of Scientific and Technical Information of China (English)

    缪长喜; 华伟明; 陈建民; 高滋

    1996-01-01

    A series of sulfated binary and trinary oxide solid superacids were prepared, and their catalytic activities for n-butane isomerization at low temperature were measured. The incorporation of different metal oxides into ZrO2 may produce a positive or negative effect on the acid strength and catalytic activity of the solid superacids. Sulfated oxides of Cr-Zr, Fe-Cr-Zr and Fe-V-Zr are 2 - 3 times more active than the reported sulfated Fe-Mn-Zr oxide. The enhancement in the superacidity and catalytic activity of these new solid superacids has been discussed on account of the results of various characteriation techniques.

  7. Chlorate: a reversible inhibitor of proteoglycan sulfation

    Energy Technology Data Exchange (ETDEWEB)

    Humphries, D.E.; Silbert, J.E.

    1988-07-15

    Bovine aorta endothelial cells were cultured in medium containing (/sup 3/H)glucosamine, (/sup 35/S)sulfate, and various concentrations of chlorate. Cell growth was not affected by 10 mM chlorate, while 30 mM chlorate had a slight inhibitory effect. Chlorate concentrations greater than 10 mM resulted in significant undersulfation of chondroitin. With 30 mM chlorate, sulfation of chondroitin was reduced to 10% and heparan to 35% of controls, but (/sup 3/H)glucosamine incorporation on a per cell basis did not appear to be inhibited. Removal of chlorate from the culture medium of cells resulted in the rapid resumption of sulfation.

  8. Addition of dehydroepiandrosterone (DHEA) for poor-responder patients before and during IVF treatment improves the pregnancy rate: a randomized prospective study.

    Science.gov (United States)

    Wiser, A; Gonen, O; Ghetler, Y; Shavit, T; Berkovitz, A; Shulman, A

    2010-10-01

    The aim of this study was to evaluate the effect of dehydroepiandrosterone (DHEA) supplementation on in vitro fertilization (IVF) data and outcomes among poor-responder patients. A randomized, prospective, controlled study was conducted. All patients received the long-protocol IVF. Those in the study group received 75 mg of DHEA once a day before starting the next IVF cycle and during treatment. Thirty-three women with significantly diminished ovarian reserves were enrolled, 17 in the DHEA group and 16 in the control group. The 33 patients underwent 51 IVF cycles. The DHEA group demonstrated a non-significant improvement in estradiol levels on day of hCG (P = 0.09) and improved embryo quality during treatment (P = 0.04) between first and second cycles. Patients in the DHEA group also had a significantly higher live birth rate compared with controls (23.1% versus 4.0%; P = 0.05), respectively. Six of seven deliveries were among patients with secondary infertility (P = 0.006). Dehydroepiandrosterone supplementation can have a beneficial effect on ovarian reserves for poor-responder patients on IVF treatment. Clinicaltrials.gov: NCT01145144.

  9. Impact of dehydroepiandrosterone on clinical outcome in poor responders: A pilot study in women undergoing in vitro fertilization, using bologna criteria

    Directory of Open Access Journals (Sweden)

    Padma Rekha Jirge

    2014-01-01

    Full Text Available Objective: To evaluate the role of dehydroepiandrosterone (DHEA supplementation in women with poor ovarian response (POR undergoing in vitro fertilization (IVF. Design: Prospective case-control study. Setting: Private tertiary fertility clinic. MATERIALS AND Methods: 31 infertile women with POR diagnosed as per the Bologna criteria. Interventions: DHEA supplementation for 2 months and a subsequent IVF cycle, after two previous IVF cycles with POR. Main Outcome Measure(S: Dose and duration of gonadotropin therapy, oocyte yield, embryo number and quality, pregnancy and live birth rate. Results: No difference was seen in gonadotropin requirement before and after DHEA supplementation. There was a significant increase in total and metaphase II oocytes (5.9 ± 0.68 vs. 2.73 ± 0.24; 4.45 ± 0.47 vs. 2.09 ± 0.26, fertilization (3.65 ± 0.49 vs. 2.00 ± 0.27, Grade I embryos (1.52 ± 0.25 vs. 0.55 ± 0.18, pregnancy rate (30% vs. 9.1% and live birth rate (25% vs 0% in those who completed the cycle, following DHEA supplementation. Conclusions: Dehydroepiandrosterone supplementation results in an improvement in oocyte yield, embryo quality, and live birth rate in a group of women with POR having undergone at least two previous failures due to POR.

  10. The Effect of Dehydroepiandrosterone on the Expression of AT1 receptor and TNF-induced ICAM-1 in Vascular Smooth Muscle Cells

    Institute of Scientific and Technical Information of China (English)

    Wu Saizhu; Wang Zidong; Zhou Zhongjiang; Zhou Kexiang; Wu Yanxian; Sun Fei; Rong Zhiyi; Ma Rui; Wei Heming

    2005-01-01

    Objectives To further investigate the molecular mechanism of vasoprotective role of dehydroepiandrosterone (DHEA), we examined DHEA on AT1 receptor and ICAM-1 gene expression in vascular smooth muscle cells (VSMCs). Methods RT-PCR and Western Blot was used to determine the change of the expressions of mRNA and protein of AT1 and ICAM-1 when given various concentration dehydroepiandrosterone. Results 1.AT1 was abundant under the basal condition. The expression of AT1 mRNA and protein decreased after stimulated by DHEA (at 10-10mol/L , 10-8 mol/L, 10-6 mol/L), and the effects of DHEA on AT1 protein was dose-dependent. ER inhibitor Tamoxifen and AR inhibitor Flutamide enhanced AT1 protein expression, but did not influence the mRNA expression. 2. The exp-ression of ICAM-1 gene was low under the basal condition. It increased when induced by TNF-α,but decreased when induced by DHEA (at l0-10 mol/L, 10-8 mol/L, 10-6 mol/L) ,and the effects of DHEA on ICAM-1 gene expression were dose-dependent. Conclusions These findings suggest that DHEA modulates AT1 and inflammatory factor induced ICAM-1 gene expression in VSMC, but further studies are necessary in the mecha-nism of DHEA action.

  11. Sulfated cellulose thin films with antithrombin affinity

    Directory of Open Access Journals (Sweden)

    2009-11-01

    Full Text Available Cellulose thin films were chemically modified by in situ sulfation to produce surfaces with anticoagulant characteristics. Two celluloses differing in their degree of polymerization (DP: CEL I (DP 215–240 and CEL II (DP 1300–1400 were tethered to maleic anhydride copolymer (MA layers and subsequently exposed to SO3•NMe3 solutions at elevated temperature. The impact of the resulting sulfation on the physicochemical properties of the cellulose films was investigated with respect to film thickness, atomic composition, wettability and roughness. The sulfation was optimized to gain a maximal surface concentration of sulfate groups. The scavenging of antithrombin (AT by the surfaces was determined to conclude on their potential anticoagulant properties.

  12. ROE Wet Sulfate Deposition 2009-2011

    Data.gov (United States)

    U.S. Environmental Protection Agency — The raster data represent the amount of wet sulfate deposition in kilograms per hectare from 2009 to 2011. Summary data in this indicator were provided by EPA’s...

  13. Sulfate reduction and methanogenesis at a freshwater

    DEFF Research Database (Denmark)

    Iversen, Vibeke Margrethe Nyvang; Andersen, Martin Søgaard; Jakobsen, Rasmus

    The freshwater-seawater interface was studied in a ~9-m thick anaerobic aquifer located in marine sand and gravel with thin peat lenses. Very limited amounts of iron-oxides are present. Consequently, the dominating redox processes are sulfate reduction and methanogenesis, and the groundwater...... is enriched in dissolved sulfide, methane and bicarbonate. Under normal conditions the seawater-freshwater interface is found at a depth of 4 m at the coastline and reaches the bottom of the aquifer 40 m inland. However, occasional flooding of the area occurs, introducing sulfate to the aquifer. Groundwater...... chemistry was studied in a 120 m transect perpendicular to the coast. Cores were taken for radiotracer rate measurements of sulfate reduction and methanogenesis. In the saline part of the aquifer 35 m inland, sulfate reduction was the dominant process with rates of 0.1-10 mM/year. In the freshwater part 100...

  14. Sulfate reduction and methanogenesis at a freshwater

    DEFF Research Database (Denmark)

    Iversen, Vibeke Margrethe Nyvang; Andersen, Martin Søgaard; Jakobsen, Rasmus

    The freshwater-seawater interface was studied in a ~9-m thick anaerobic aquifer located in marine sand and gravel with thin peat lenses. Very limited amounts of iron-oxides are present. Consequently, the dominating redox processes are sulfate reduction and methanogenesis, and the groundwater...... is enriched in dissolved sulfide, methane and bicarbonate. Under normal conditions the seawater-freshwater interface is found at a depth of 4 m at the coastline and reaches the bottom of the aquifer 40 m inland. However, occasional flooding of the area occurs, introducing sulfate to the aquifer. Groundwater...... chemistry was studied in a 120 m transect perpendicular to the coast. Cores were taken for radiotracer rate measurements of sulfate reduction and methanogenesis. In the saline part of the aquifer 35 m inland, sulfate reduction was the dominant process with rates of 0.1-10 mM/year. In the freshwater part 100...

  15. Sulfate Resistance of Alkali Activated Pozzolans

    OpenAIRE

    Bondar, Dali

    2015-01-01

    The consequence of sulfate attack on geopolymer concrete, made from an alkali activated natural pozzolan (AANP) has been studied in this paper. Changes in the compressive strength, expansion and capillary water absorption of specimens have been investigated combined with phases determination by means of X-ray diffraction. At the end of present investigation which was to evaluate the performance of natural alumina silica based geopolymer concrete in sodium and magnesium sulfate solution, the l...

  16. Is there a correlation between structure and anticoagulant action of sulfated galactans and sulfated fucans?

    Science.gov (United States)

    Pereira, Mariana S; Melo, Fábio R; Mourão, Paulo A S

    2002-10-01

    We attempted to identify the specific structural features in sulfated galactans and sulfated fucans that confer anticoagulant activity. For this study we employed a variety of invertebrate polysaccharides with simple structures composed of well-defined units of oligosaccharides. Our results indicate that a 2-O-sulfated, 3-linked alpha-L-galactan, but not a alpha-L-fucan with a similar molecular size, is a potent thrombin inhibitor mediated by antithrombin or heparin cofactor II. The difference between the activities of these two polysaccharides is not very pronounced when factor Xa replaced thrombin. The occurrence of 2,4-di-O-sulfated units is an amplifying motif for 3-linked alpha-fucan-enhanced thrombin inhibition by antithrombin. If we replace antithrombin by heparin cofactor II, then the major structural requirement for the activity becomes single 4-O-sulfated fucose units. The presence of 2-O-sulfated fucose residues always had a deleterious effect on anticoagulant activity. Overall, our results indicate that the structural requirements for interaction of sulfated galactans and sulfated fucans with coagulation cofactors and their target proteases are stereospecific and not merely a consequence of their charge density and sulfate content.

  17. Hormonal control of sulfate uptake and assimilation.

    Science.gov (United States)

    Koprivova, Anna; Kopriva, Stanislav

    2016-08-01

    Plant hormones have a plethora of functions in control of plant development, stress response, and primary metabolism, including nutrient homeostasis. In the plant nutrition, the interplay of hormones with responses to nitrate and phosphate deficiency is well described, but relatively little is known about the interaction between phytohormones and regulation of sulfur metabolism. As for other nutrients, sulfate deficiency results in modulation of root architecture, where hormones are expected to play an important role. Accordingly, sulfate deficiency induces genes involved in metabolism of tryptophane and auxin. Also jasmonate biosynthesis is induced, pointing to the need of increase the defense capabilities of the plants when sulfur is limiting. However, hormones affect also sulfate uptake and assimilation. The pathway is coordinately induced by jasmonate and the key enzyme, adenosine 5'-phosphosulfate reductase, is additionally regulated by ethylene, abscisic acid, nitric oxid, and other phytohormones. Perhaps the most intriguing link between hormones and sulfate assimilation is the fact that the main regulator of the response to sulfate starvation, SULFATE LIMITATION1 (SLIM1) belongs to the family of ethylene related transcription factors. We will review the current knowledge of interplay between phytohormones and control of sulfur metabolism and discuss the main open questions.

  18. Ammonium sulfate preparation from phosphogypsum waste

    Directory of Open Access Journals (Sweden)

    Abdel-Hakim T. Kandil

    2017-01-01

    Full Text Available The Egyptian phosphogypsum waste is treated using sulfuric acid prior the ammonium sulfate production. The relevant factors that would affect the removal efficiencies of some impurities are studied. The optimum conditions of the treatment are 8 M sulfuric acid solution and 1/4 solid/liquid ratio for 30 min contact time at 80 °C. Moreover, the optimum conditions of the ammonium sulfate preparation are 10 g of the suspended impure or purified phosphogypsum in 40 ml of 3% ammonium sulfate solution (as initiator, 1/4 solid/liquid ratio at pH7 at an addition of an excess ammonium carbonate, and 150 rpm stirring speed for 4.0 h contact time at 55 °C as well as the 5 mg of barium chloride is added to remove the radium in the ammonium sulfate product. Finally, the ammonium sulfate is crystallized and the chemical analysis of the product shows 20% nitrogen and 23.6% sulfur. Therefore, the purity of the obtained ammonium sulfate is 95% from the purified phosphogypsum.

  19. Preparation of Agarose Sulfate and Its Antithrombogenicity

    Institute of Scientific and Technical Information of China (English)

    JIE Youping; ZHANG Lingmin; CHEN Peng; MAO Xuan; TANG Shunqing

    2012-01-01

    As one of the seaweed polysaccharide,agarose has received much attention because of its biocompatibility.However,its application in biomedical field was limited with its biological inertia.Modification with some functional groups is needed to obtain agarose derivatives with biological activity and expand its applications.Consequently,agarose was sulfated with chlorosulfonic acid-pyridine with formamide as dispersing agent.The orthogonal test result showed that the optimal reaction condition was the reaction time being 4 h,the reaction temperature 65 ℃,and the ratio of chlorosulfonic acid to agarose 1-4(mL/g).Two kinds of the insoluble agarose sulfate (below 37 ℃) were synthesized with degree of substitution (DS) being 0.17 and 0.43 respectively.Infrared spectroscopy (IR) and 13C nuclear magnetic resonance (13C-NMR) spectroscopy results proved that C3-6 in agarose was sulfated.Their hydrophobic property and BSA adsorption capacity rose with increasing DS,while the adsorption of Hb was reduced.The anti-clotting properties of agarose sulfate were significantly improved,and agarose sulfate could protect red blood cells from deformation after adsorption of BSA.These findings demonstrate that the cold-water insoluble agarose sulfate has a promise for applications as heparin-like material in anticoagulation or endothelial regeneration scaffold.

  20. Structure of a rat hepatoma heparan sulfate

    Energy Technology Data Exchange (ETDEWEB)

    Fedarko, N.S.; Ishihara, M.; Conrad, H.E.

    1986-05-01

    Previous studies showed that as monolayer cultures of a rat hepatocyte cell line passed from log growth to confluency there was an increase in sulfation of heparan sulfate (HS) and the accumulation of a unique species of HS with a high content of sulfated GlcA residues in the nucleus. The present study compares the HS metabolism of a rat (Morris) hepatoma line. Cells were labeled with /sup 35/SO/sub 4//sup 2 -/ and the structure and distribution of (/sup 35/SO/sub 4/)HS from the culture medium (CM), the pericellular matrix (Ma), the nucleus (NUC), the outer nuclear membrane (NM), and the remaining cytoplasmic (CP) pool was measured as nitrous acid-susceptible material. The amount of label incorporated into each pool was 1/10 that observed in the hepatocyte line. The HS proteglycan and the free HS chains from the hepatoma showed size distributions similar to those found for the hepatocytes, but a lower average charge density. In the HS from the CM, Ma, and CP pools 56% of glucosamine residues were sulfated; in that from the NM and NUC pools 46% were sulfated. HONO treatment gave mono- and disulfated disaccharides in a ratio of 1.5:1 for all five cellular pools, but showed that the HS from the NUC pool did not contain high levels of sulfated GlcA residues.

  1. Lack of influence of dyspareunia on the beneficial effect of intravaginal prasterone (dehydroepiandrosterone, DHEA) on sexual dysfunction in postmenopausal women.

    Science.gov (United States)

    Labrie, Fernand; Archer, David; Bouchard, Céline; Fortier, Michel; Cusan, Leonello; Gomez, José-Luis; Girard, Ginette; Baron, Mira; Ayotte, Normand; Moreau, Michèle; Dubé, Robert; Côté, Isabelle; Labrie, Claude; Lavoie, Lyne; Gilbert, Lucy; Martel, Céline; Balser, John

    2014-07-01

    We have previously observed that intravaginal prasterone (dehydroepiandrosterone, DHEA) improved all domains of female sexual dysfunction (FSD). Investigate the influence of moderate/severe pain at sexual activity (dyspareunia) (MSD) at baseline on FSD following prasterone administration. The effect of daily administration of prasterone (0, 3.25 mg, 6.5 mg or 13 mg) for 12 weeks on FSD in 215 postmenopausal women with or without MSD at baseline was evaluated in a prospective, randomized, double-blind, and placebo-controlled phase III clinical trial. Differences were examined on desire, arousal and orgasm. Comparable benefits were observed in women not having MSD (n = 56) vs. those having MSD (n = 159). The benefits over placebo in prasterone-treated women for desire, avoiding intimacy and vaginal dryness as well as for the total sexual domain of the MENQOL (Menopause Specific Quality of Life) questionnaire, ranged between 18.0% and 38.2% with P values of <0.05 or <0.01 except in one out of 12 subgroups. For the arousal/sensation, arousal/lubrication and summary score of the ASF (Abbreviated Sexual Function) questionnaire, in the MSD+ group, improvements of 64.2% (P = 0.01), 118% (P = 0.001) and 31.1% (P = 0.03) were observed over placebo, respectively, while similar differences (58.0%, 67.6% and 32.1%) did not reach statistical significance in the MSD- group having up to only 44 prasterone-treated women compared with 119 in the MSD+ group. No MSD at baseline does not apparently affect the effects of intravaginal prasterone on sexual dysfunction. Knowing the absence of significant effects of estrogens on FSD, the present data suggest that vulvovaginal atrophy (VVA) and vulvovaginal sexual dysfunction (VVSD) are two different consequences of sex steroid deficiency at menopause which can respond independently. In addition, the present data seriously question the justification of pain being part of FSD as well as the separation of FSD into

  2. Reduced quality and accelerated follicle loss with female reproductive aging - does decline in theca dehydroepiandrosterone (DHEA) underlie the problem?

    Science.gov (United States)

    Ford, Judith H

    2013-12-13

    Infertility, spontaneous abortion and conception of trisomic offspring increase exponentially with age in mammals but in women there is an apparent acceleration in the rate from about age 37. The problems mostly commonly occur when the ovarian pool of follicles is depleted to a critical level with age but are also found in low follicular reserve of other etiologies. Since recent clinical studies have indicated that dehydroepiandrosterone (DHEA) supplementation may reverse the problem of oocyte quality, this review of the literature was undertaken in an attempt to find an explanation of why this is effective? In affected ovaries, oxygenation of follicular fluid is low, ultrastructural disturbances especially of mitochondria, occur in granulosa cells and oocytes, and considerable disturbances of meiosis occur. There is, however, no evidence to date that primordial follicles are compromised. In females with normal fertility, pre-antral ovarian theca cells respond to stimulation by inhibin B to provide androgen-based support for the developing follicle. With depletion of follicle numbers, inhibin B is reduced with consequent reduction in theca DHEA. Theca cells are the sole ovarian site of synthesis of DHEA, which is both a precursor of androstenedione and an essential ligand for peroxisome proliferator-activated receptor alpha (PPARα), the key promoter of genes affecting fatty acid metabolism and fat transport and genes critical to mitochondrial function. As well as inducing a plethora of deleterious changes in follicular cytoplasmic structure and function, the omega 9 palmitate/oleate ratio is increased by lowered activity of PPARα. This provides conditions for increased ceramide synthesis and follicular loss through ceramide-induced apoptosis is accelerated. In humans critical theca DHEA synthesis occurs at about 70 days prior to ovulation thus effective supplementation needs to be undertaken about four months prior to intended conception; timing which is also

  3. Dehydroepiandrosterone Supplementation Combined with Whole-Body Vibration Training Affects Testosterone Level and Body Composition in Mice

    Science.gov (United States)

    Chen, Wen-Chyuan; Chen, Yi-Ming; Huang, Chi-Chang; Tzeng, Yen-Dun

    2016-01-01

    Dehydroepiandrosterone (DHEA), the most abundant sex steroid, is primarily secreted by the adrenal gland and a precursor hormone used by athletes for performance enhancement. Whole-body vibration (WBV) is a well-known light-resistance exercise by automatic adaptations to rapid and repeated oscillations from a vibrating platform, which is also a simple and convenient exercise for older adults. However, the potential effects of DHEA supplementation combined with WBV training on to body composition, exercise performance, and hormone regulation are currently unclear. The objective of the study is to investigate the effects of DHEA supplementation combined with WBV training on body composition, exercise performance, and physical fatigue-related biochemical responses and testosterone content in young-adult C57BL/6 mice. In this study, male C57BL/6 mice were divided into four groups (n = 8 per group) for 6-weeks treatment: sedentary controls with vehicle (SC), DHEA supplementation (DHEA, 10.2 mg/kg), WBV training (WBV; 5.6 Hz, 2 mm, 0.13 g), and WBV training with DHEA supplementation (WBV+DHEA; WBV: 5.6 Hz, 2 mm, 0.13 g and DHEA: 10.2 mg/kg). Exercise performance was evaluated by forelimb grip strength and exhaustive swimming time, as well as changes in body composition and anti-fatigue levels of serum lactate, ammonia, glucose, creatine kinase (CK), and blood urea nitrogen (BUN) after a 15-min swimming exercise. In addition, the biochemical parameters and the testosterone content were measured at the end of the experiment. Six-week DHEA supplementation alone significantly increased mice body weight (BW), muscle weight, testosterone level, and glycogen contents (liver and muscle) when compared with SC group. DHEA supplementation alone had no negative impact on all tissue and biochemical profiles, but could not improve exercise performance. However, WBV+DHEA supplementation also significantly decreased BW, testosterone level and glycogen content of liver, as well as serum

  4. Sulfated polysaccharides and cell differentiation in the sea urchin embryo.

    Science.gov (United States)

    Løvtrup-Rein, H; Løvtrup, S

    1984-01-01

    The synthesis of sulfated polysaccharides during the embryonic development of Paracentrotus lividus has been investigated by incorporation of radioactive sulfate, glucose, glucosamine and fucose. The following substances become labelled: fucan sulfate (approximately 60%), heparan sulfate (approximately 20%) and dermatan sulfate (approximately 20%), and possibly a very slight amount of chondroitin sulfate. In animalized and vegetalized embryos, the rate of incorporation is significantly reduced, and furthermore dermatan sulfate is almost absent in animalized embryos. It is concluded that this substance is associated with the differentiation of vegetative cells, possibly the mesenchyme cells.

  5. Morphological and hormonal parameters in two species of macaques: impact of seasonal breeding.

    Science.gov (United States)

    Muehlenbein, Michael P; Campbell, Benjamin C; Murchison, Mark A; Phillippi, Kathrine M

    2002-03-01

    To compare physiological and developmental differences between two cogeneric species that differ by seasonal vs. aseasonal breeding, values for morphological measurements, testicular volume, serum testosterone, estradiol, and dehydroepiandrosterone-sulfate levels were obtained from 53 rhesus during the early breeding season, as well as 41 pig-tailed macaque males maintained at the Tulane Primate Center. The two species exhibited similar body size, testosterone, and estradiol levels, but differed substantially in testicular volume (3.00 +/- 1.7 vs. 1.72 +/- 1.3 cc), abdominal skinfold measures (15.7 +/- 9.2 vs. 9.0 +/- 7.7 mm), and DHEA-S levels (18.0 +/- 11.7 vs. 7.6 +/- 5.4 microg/dl). Significant interaction effects for species by age group were found for weight, tricep circumference, length, and estradiol level. In addition, length was more closely related to testicular volume among rhesus compared to pig-tailed macaques, suggesting different developmental patterns between the species. Predictors of hormonal levels differed between the two species. In the rhesus, estradiol levels were related to testicular volume and testosterone levels while there were no anthropometric predictors of testosterone or DHEA-S. For the pig-tailed macaques, testicular volume was related to tricep circumference, testosterone to triceps skinfold and testicular volume, and estradiol to weight. It is argued that rhesus have larger testes for body size and more abdominal fat deposits during the early breeding season relative to pig-tailed macaques reflecting the increased demands of sperm competition in a seasonally breeding species. Hormonal differences associated with the difference in breeding system appear to be primarily related to adrenal rather than testicular activity.

  6. Sulfated polysaccharides and immune response: promoter or inhibitor?

    Science.gov (United States)

    Chen, D; Wu, X Z; Wen, Z Y

    2008-06-01

    Sulfated polysaccharides, which frequently connect to core protein, are expressed not only on cell surface but also throughout the extracellular matrix. Besides providing structural integrity of cells, sulfated polysaccharides interact with a variety of sulfated polysaccharides-binding proteins, such as growth factors, cytokines, chemokines and proteases. Sulfated polysaccharides play two-edged roles, inhibitor and promoter, in immune response. Some sulfated polysaccharides act as the immunosuppressor by blocking inflammatory signal transduction induced by proinflammatory cytokines, suppressing the activation of complement and inhibiting the process that leukocytes adhere to and pass through endothelium. On the contrary, the interaction between immune cells and sulfated polysaccharides produced by bacteria, endothelial cells and immune cells initiate the occurrence of immune response. It promotes the processes of recognizing and arresting antigen, migrating transendothelium, moving into and out of immune organ and enhancing the proliferation of lymphocyte. The structure of sulfated polysaccharides, such as molecular weight and sulfated sites heterogeneity, especially the degree of disaccharide sulfation, position of the sulfate moiety and organization of sulfated domains, may play critical role in their controversial effects. As a consequence, the interaction between sulfated polysaccharides and sulfated polysaccharide-binding proteins may be changed by modifying the structure of sulfated polysaccharides chains. The administration of drug targeting sulfated polysaccharide-protein interaction may be useful in treating inflammatory related diseases.

  7. On the roles and regulation of chondroitin sulfate and heparan sulfate in zebrafish pharyngeal cartilage morphogenesis

    DEFF Research Database (Denmark)

    Holmborn, Katarina; Habicher, Judith; Kasza, Zsolt;

    2012-01-01

    The present study addresses the roles of heparan sulfate (HS) proteoglycans and chondroitin sulfate (CS) proteoglycans in the development of zebrafish pharyngeal cartilage structures. uxs1 and b3gat3 mutants, predicted to have impaired biosynthesis of both HS and CS because of defective formation...

  8. 21 CFR 524.960 - Flumethasone, neomycin sulfate, and polymyxin B sulfate ophthalmic solutions.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Flumethasone, neomycin sulfate, and polymyxin B sulfate ophthalmic solutions. 524.960 Section 524.960 Food and Drugs FOOD AND DRUG ADMINISTRATION... fundamental healing mechanism. Adrenocorticoid compounds have been reported to cause an increase in...

  9. Modeling of sulfation of potassium chloride by ferric sulfate addition during grate-firing of biomass

    DEFF Research Database (Denmark)

    Wu, Hao; Jespersen, Jacob Boll; Aho, Martti

    2013-01-01

    Potassium chloride, KCl, formed from critical ash-forming elements released during combustion may lead to severe ash deposition and corrosion problems in biomass-fired boilers. Ferric sulfate, Fe2(SO4)3 is an effective additive, which produces sulfur oxides (SO2 and SO3) to convert KCl to the less...... harmful K2SO4. In the present study the decomposition of ferric sulfate is studied in a fast-heating rate thermogravimetric analyzer (TGA), and a kinetic model is proposed to describe the decomposition process. The yields of SO2 and SO3 from ferric sulfate decomposition are investigated in a laboratory......-scale tube reactor. It is revealed that approximately 40% of the sulfur is released as SO3, the remaining fraction being released as SO2. The proposed decomposition model of ferric sulfate is combined with a detailed gas phase kinetic model of KCl sulfation, and a simplified model of K2SO4 condensation...

  10. Heparin-like properties of sulfated alginates with defined sequences and sulfation degrees.

    Science.gov (United States)

    Arlov, Øystein; Aachmann, Finn Lillelund; Sundan, Anders; Espevik, Terje; Skjåk-Bræk, Gudmund

    2014-07-14

    Sulfated glycosaminoglycans have a vast range of protein interactions relevant to the development of new biomaterials and pharmaceuticals, but their characterization and application is complicated mainly due to a high structural variability and the relative difficulty to isolate large quantities of structurally homogeneous samples. Functional and versatile analogues of heparin/heparan sulfate can potentially be created from sulfated alginates, which offer structure customizability through targeted enzymatic epimerization and precise tuning of the sulfation degree. Alginates are linear polysaccharides consisting of β-D-mannuronic acid (M) and α-L-guluronic acid (G), derived from brown algae and certain bacteria. The M/G ratio and distribution of blocks are critical parameters for the physical properties of alginates and can be modified in vitro using mannuronic-C5-epimerases to introduce sequence patterns not found in nature. Alginates with homogeneous sequences (poly-M, poly-MG, and poly-G) and similar molecular weights were chemically sulfated and structurally characterized by the use of NMR and elemental analysis. These sulfated alginates were shown to bind and displace HGF from the surface of myeloma cells in a manner similar to heparin. We observed dependence on the sulfation degree (DS) as well as variation in efficacy based on the alginate monosaccharide sequence, relating to relative flexibility and charge density in the polysaccharide chains. Co-incubation with human plasma showed complement compatibility of the alginates and lowering of soluble terminal complement complex levels by sulfated alginates. The sulfated polyalternating (poly-MG) alginate proved to be the most reproducible in terms of precise sulfation degrees and showed the greatest relative degree of complement inhibition and HGF interaction, maintaining high activity at low DS values.

  11. Immunohistochemical localization of chondroitin sulfate, chondroitin sulfate proteoglycan, heparan sulfate proteoglycan, entactin, and laminin in basement membranes of postnatal developing and adult rat lungs

    DEFF Research Database (Denmark)

    Sannes, P L; Burch, K K; Khosla, J

    1993-01-01

    Histologic preparations of lungs from 1-, 5-, 10-, 18-, and 25-day-old postnatal and adult rats were examined immunohistochemically with antibodies specific against chondroitin sulfate (CS), basement membrane chondroitin sulfate proteoglycan (BM-CSPG), heparan sulfate proteoglycan (HSPG), entactin...

  12. p-Cresyl sulfate and indoxyl sulfate in pediatric patients on chronic dialysis

    Directory of Open Access Journals (Sweden)

    Hye Sun Hyun

    2013-04-01

    Full Text Available &lt;b&gt;Purpose:&lt;/b&gt; Indoxyl sulfate and p- cresyl sulfate are important protein-bound uremic retention solutes whose levels can be partially reduced by renal replacement therapy. These solutes originate from intestinal bacterial protein fermentation and are associated with cardiovascular outcomes and chronic kidney disease progression. The aims of this study were to investigate the levels of indoxyl sulfate and p- cresyl sulfate as well as the effect of probiotics on reducing the levels of uremic toxins in pediatric patients on dialysis. &lt;b&gt;Methods:&lt;/b&gt; We enrolled 20 pediatric patients undergoing chronic dialysis; 16 patients completed the study. The patients underwent a 12-week regimen of VSL#3, a high-concentration probiotic preparation, and the serum levels of indoxyl sulfate and p- cresyl sulfate were measured before treatment and at 4, 8, and 12 weeks after the regimen by using fluorescence liquid chromatography. To assess the normal range of indoxyl sulfate and p- cresyl sulfate we enrolled the 16 children with normal glomerular filtration rate who had visited an outpatient clinic for asymptomatic microscopic hematuria that had been detected by a school screening in August 2011. &lt;b&gt;Results:&lt;/b&gt; The baseline serum levels of indoxyl sulfate and p- cresyl sulfate in the patients on chronic dialysis were significantly higher than those in the children with microscopic hematuria. The baseline serum levels of p- cresyl sulfate in the peritoneal dialysis group were significantly higher than those in the hemodialysis group. There were no significant changes in the levels of these uremic solutes after 12-week VSL#3 treatment in the patients on chronic dialysis. &lt;b&gt;Conclusion:&lt;/b&gt; The levels of the uremic toxins p- cresyl sulfate and indoxyl sulfate are highly elevated in pediatric patients on dialysis, but there was no significant effect by

  13. A prospective study on role of dehydroepiandrosterone (DHEA) on improving the ovarian reserve markers in infertile patients with poor ovarian reserve.

    Science.gov (United States)

    Singh, Neeta; Zangmo, Rinchen; Kumar, Sunesh; Roy, K K; Sharma, J B; Malhotra, Neena; Vanamail, Perumal

    2013-11-01

    The aim of this study was to evaluate the role of dehydroepiandrosterone (DHEA) supplementation on the ovarian reserve markers in infertile patients who were poor responders in previous in vitro fertilization (IVF) cycles. A prospective clinical trial was conducted on 30 patients with history of poor response in previous IVF cycles. These patients were treated with DHEA, (Tab Eema-D, Corona Remedies Pvt Ltd., Ahmedabad, Gujurat, India) 25 mg thrice a day for four months. Ovarian stimulation was done using the previous protocol. Clinical parameters were measured before and treatment with DHEA. Results were analysed using Student's "t" paired test. DHEA resulted in a significant increase (p 38 years). Peak estradiol level on the day of human chorionic gonadotrophin administration also increased significantly (p DHEA has a significant effect in improving the ovarian reserve in poor responders with previously failed IVF cycles. It can help in enhancing clinical pregnancy rate in these patients.

  14. Psychological job strain, social support at work and daytime secretion of dehydroepiandrosterone (DHEA) in healthy female employees: cross-sectional analyses.

    Science.gov (United States)

    Ota, Atsuhiko; Yatsuya, Hiroshi; Mase, Junji; Ono, Yuichiro

    2015-11-10

    Evidence is limited concerning the influences of high psychological job strain and low social support at work on daytime secretion of dehydroepiandrosterone (DHEA), which demonstrates anti-cortisol effects. We carried out a cross-sectional study to examine the associations of job strain and social support with daytime secretion amounts of DHEA and cortisol and daytime variation of the cortisol-to-DHEA ratio (C/D ratio) in healthy female workers. Study subjects comprised 115 healthy female nursery school teachers. Area under the curve with respect to ground (AUCG) of salivary DHEA, cortisol and C/D ratio was calculated for estimation of daytime secretion and variation. Social support scores were negatively associated with daytime DHEA secretion (standardized partial regression coefficient = -0.343, P DHEA, cortisol or the C/D ratio. In summary, we found that daytime DHEA secretion was increased in healthy workers with low social support, perhaps independent of daytime cortisol secretion.

  15. Sulfate-reducing bacteria: Microbiology and physiology

    Science.gov (United States)

    Peck, H. D.

    1985-01-01

    The sulfate reducing bacteria, the first nonphotosynthetic anaerobic bacteria demonstrated to contain c type cytochromes, perform electron transfer coupled to phosphorylation. A new bioenergetic scheme for the formation of a proton gradient for growth of Desulfovibrio on organic substrates and sulfate involving vectors electron transfer and consistent with the cellular localization of enzymes and electron transfer components was proposed. Hydrogen is produced in the cytoplasm from organic substrates and, as a permease molecule diffuses rapidly across the cytoplasmic membrane, it is oxidized to protons and electrons by the periplasmic hydrogenase. The electrons only are transferred across the cytoplasmic membrane to the cytoplasm where they are used to reduce sulfate to sulfide. The protons are used for transport or to drive a reversible ATPOSE. The net effect is the transfer of protons across the cytoplasmic membrane with the intervention of a proton pump. This type of H2 cycling is relevant to the bioenergetics of other types of anaerobic microorganisms.

  16. Sulfated glycopeptide nanostructures for multipotent protein activation

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sungsoo S.; Fyrner, Timmy; Chen, Feng; Álvarez, Zaida; Sleep, Eduard; Chun, Danielle S.; Weiner, Joseph A.; Cook, Ralph W.; Freshman, Ryan D.; Schallmo, Michael S.; Katchko, Karina M.; Schneider, Andrew D.; Smith, Justin T.; Yun, Chawon; Singh, Gurmit; Hashmi, Sohaib Z.; McClendon, Mark T.; Yu, Zhilin; Stock, Stuart R.; Hsu, Wellington K.; Hsu, Erin L.; Stupp , Samuel I. (NWU)

    2017-06-19

    Biological systems have evolved to utilize numerous proteins with capacity to bind polysaccharides for the purpose of optimizing their function. A well-known subset of these proteins with binding domains for the highly diverse sulfated polysaccharides are important growth factors involved in biological development and tissue repair. We report here on supramolecular sulfated glycopeptide nanostructures, which display a trisulfated monosaccharide on their surfaces and bind five critical proteins with different polysaccharide-binding domains. Binding does not disrupt the filamentous shape of the nanostructures or their internal β-sheet backbone, but must involve accessible adaptive configurations to interact with such different proteins. The glycopeptide nanostructures amplified signalling of bone morphogenetic protein 2 significantly more than the natural sulfated polysaccharide heparin, and promoted regeneration of bone in the spine with a protein dose that is 100-fold lower than that required in the animal model. These highly bioactive nanostructures may enable many therapies in the future involving proteins.

  17. Movement disorder, memory, psychiatric symptoms and serum DHEA levels in schizophrenic and schizoaffective patients.

    Science.gov (United States)

    Harris, D S; Wolkowitz, O M; Reus, V I

    2001-04-01

    Reports of low levels of dehydroepiandrosterone (DHEA) or its sulphate (DHEA-S) in some schizophrenic patients and in some persons with poorer motoric and cognitive functioning led us to examine clinical correlates of serum DHEA and DHEA-S levels in schizophrenic patients. Ratings of abnormal movements, memory and psychiatric symptoms in 17 medicated chronic schizophrenic or schizoaffective inpatients at a state hospital were correlated with serum DHEA and DHEA-S levels, and their ratios with serum cortisol. Controlling for age, higher DHEA levels and/or higher DHEA/cortisol ratios were significantly correlated with lower symptom ratings on the Brief Psychiatric Rating Scale, better performance on some measures of memory, and lower ratings of parkinsonian symptoms. Relatively low DHEA levels or DHEA/cortisol ratios may identify a particularly impaired subgroup of medicated patients with chronic schizophrenia. Potential implications are discussed.

  18. Formation of the natural sulfate aerosol

    Energy Technology Data Exchange (ETDEWEB)

    Kerminen, V.M.; Hillamo, R.; Maekinen, M.; Virkkula, A.; Maekelae, T.; Pakkanen, T. [Helsinki Univ. (Finland). Dept. of Physics

    1996-12-31

    Anthropogenic sulfate aerosol, together with particles from biomass burning, may significantly reduce the climatic warming due to man-made greenhouse gases. The radiative forcing of aerosol particles is based on their ability to scatter and absorb solar radiation (direct effect), and on their influences on cloud albedos and lifetimes (indirect effect). The direct aerosol effect depends strongly on the size, number and chemical composition of particles, being greatest for particles of 0.1-1 {mu}m in diameter. The indirect aerosol effect is dictated by the number of particles being able to act as cloud condensation nuclei (CCN). For sulfate particles, the minimum CCN size in tropospheric clouds is of the order of 0.05-0.2 {mu}m. To improve aerosol parameterizations in future climate models, it is required that (1) both primary and secondary sources of various particle types will be characterized at a greater accuracy, and (2) the influences of various atmospheric processes on the spatial and temporal distribution of these particles and their physico-chemical properties are known much better than at the present. In estimating the climatic forcing due to the sulfate particles, one of the major problems is to distinguish between sulfur from anthropogenic sources and that of natural origin. Global emissions of biogenic and anthropogenic sulfate pre-cursors are comparable in magnitude, but over regional scales either of these two source types may dominate. The current presentation is devoted to discussing the natural sulfate aerosol, including the formation of sulfur-derived particles in the marine environment, and the use of particulate methanesulfonic acid (MSA) as a tracer for the natural sulfate

  19. Synthesis and antimicrobial activities of dehydroepiandrosterone oxime acetate%醋酸去氢表雄酮肟的合成及其抗菌活性研究

    Institute of Scientific and Technical Information of China (English)

    田光辉

    2012-01-01

    以醋酸去氢表雄酮为原料,室温搅拌下和盐酸羟胺在弱碱性介质中反应合成醋酸去氢表雄酮肟,得到了纯度较高的醋酸去氢表雄酮肟,收率达89.6%.通过测定其熔点,借助紫外光谱(UV)、红外光谱(IR)、核磁共振谱( NMR)、质谱(MS)以及元素分析等技术来表征其结构.抗菌活性实验表明,醋酸去氢表雄酮肟对实验菌株均有抑制和灭活作用,对枯草芽胞杆菌CMCC63501株的作用表现得更为明显.%The target compound 3-β-hydroxy-deoxyandrost-5-ene-17-one oxime-3-acetate was synthesized in alkalescence medium with 3-β-hydroxy-deoxyandrost-5-ene-17-one-3-acetate and hydroxyla-mine hydrochloride at room temperature by churn-dasher, purer dehydroepiandrosterone oxime acetate was obtained and its yield reached 89. 6%. The melting point of this target compound was determined and its structure was fully characterized by UV, IR, NMR, MS and elemental analysis. The antimicrobial activities of dehydroepiandrosterone oxime acetate was evaluated by inhibiting the growth of four bacteria. The results showed that the target compound inhibited the growth of testing bacteria and sterilized them, and showed higher antimicrobial activity especially against bacillus subtillis CMCC63S01.

  20. Stress Biomarkers in Medical Students Participating in a Mind Body Medicine Skills Program

    Directory of Open Access Journals (Sweden)

    Brian W. MacLaughlin

    2011-01-01

    Full Text Available Georgetown University School of Medicine offers an elective Mind-Body Medicine Skills (MBMS course to medical students to promote self-care and self-awareness. Participating medical students reported better management of academic stress and well-being than non-participants. In this study, we sought to assess the stress-reducing effects of MBMS by measuring physiological changes in first-year medical students. Saliva samples were collected before (January, time 1 (T1-pre-intervention and upon completion of the course (May, time 2 (T2p-post-intervention, as well as from non-participating medical students (May, time 2 (T2c-control. The T2p and T2c collections coincided with the period of final examinations. Cortisol, dehydroepiandrosterone-sulfate (DHEA-S, testosterone and secretory immunoglobulin A (sIgA were measured. The mean morning salivary cortisol at T2p was 97% of the mean at baseline T1 which was significantly lower than for T2c (2.4 (95% confidence interval (CI 0.57–1.60, P =  .001; DHEA-S showed similar pattern as cortisol where the T2p levels were significantly lower than T2c (P <  .001 in both morning and evening collections. Testosterone ratio at T2p (0.85 was also lower than T2c (1.6 (95% CI 0.53–1.3, P =  .01. sIgA levels were not statistically different. On direct comparison, the T2c and T2p means were significantly different for all cortisol, DHEA-S and testosterone values. Participants maintained their hormonal balance within the normal range throughout the academic semester while the control group showed significantly increased levels, probably exacerbated by the end of the semester exam stress. To our knowledge, this is the first study to assess the physiologic benefits of a MBMS program in medical students.

  1. Molybdate transport through the plant sulfate transporter SHST1.

    Science.gov (United States)

    Fitzpatrick, Kate L; Tyerman, Stephen D; Kaiser, Brent N

    2008-04-30

    Molybdenum is an essential micronutrient required by plants. The mechanism of molybdenum uptake in plants is poorly understood, however, evidence has suggested that sulfate transporters may be involved. The sulfate transporter from Stylosanthes hamata, SHST1, restored growth of the sulfate transport yeast mutant, YSD1, on media containing low amounts of molybdate. Kinetic analysis using 99MoO4(2-) demonstrated that SHST1 enhanced the uptake of molybdate into yeast cells at nM concentrations. Uptake was not inhibited by sulfate, but sulfate transport via SHST1 was reduced with molybdate. These results are the first measurement of molybdate transport by a characterised plant sulfate transport protein.

  2. On the evaporation of ammonium sulfate solution

    Energy Technology Data Exchange (ETDEWEB)

    Drisdell, Walter S.; Saykally, Richard J.; Cohen, Ronald C.

    2009-07-16

    Aqueous evaporation and condensation kinetics are poorly understood, and uncertainties in their rates affect predictions of cloud behavior and therefore climate. We measured the cooling rate of 3 M ammonium sulfate droplets undergoing free evaporation via Raman thermometry. Analysis of the measurements yields a value of 0.58 {+-} 0.05 for the evaporation coefficient, identical to that previously determined for pure water. These results imply that subsaturated aqueous ammonium sulfate, which is the most abundant inorganic component of atmospheric aerosol, does not affect the vapor-liquid exchange mechanism for cloud droplets, despite reducing the saturation vapor pressure of water significantly.

  3. Selective sulfation of carrageenans and the influence of sulfate regiochemistry on anticoagulant properties.

    Science.gov (United States)

    de Araújo, Cristiano A; Noseda, Miguel D; Cipriani, Thales R; Gonçalves, Alan G; Duarte, Maria Eugênia R; Ducatti, Diogo R B

    2013-01-16

    Sulfated polysaccharides are recognized for their broad range of biological activities, including anticoagulant properties. The positions occupied by the sulfate groups are often related to the level of the inherent biological activity. Herein the naturally sulfated galactans, kappa-, iota- and theta-carrageenan, were additionally sulfated by regioselective means. The anticoagulant activity of the resulting samples was then studied using the aPTT in vitro assay. The influence of sulfate regiochemistry on the anticoagulant activity was evaluated. From kappa-carrageenan three rare polysaccharides were synthesized, one of them involved a synthetic route with an amphiphilic polysaccharide intermediate containing pivaloyl groups. Iota- and theta-carrageenan were utilized in a selective C6 sulfation at β-D-Galp units to produce different structures comprising trisulfated diads. All the samples were characterized by NMR (1D and 2D). The resulting aPPT measurements suggested that sulfation at C2 of 3,6-anhydro-α-D-Galp and C6 of β-D-Galp increased the anticoagulant activity.

  4. Activation and transfer of sulfate in biological systems (1960); Activation biologique du sulfate et son transfert (1960)

    Energy Technology Data Exchange (ETDEWEB)

    Chapeville, F. [Commissariat a l' Energie Atomique, Saclay (France).Centre d' Etudes Nucleaires

    1960-07-01

    It examines in this review the successive stages of active sulfate formation and its role in biological synthesis of sulfuric esters. The possible role of active sulfate as intermediary in sulfate reduction is also discussed. (author) [French] On examine dans cette etude les stades successifs de la mise en evidence du sulfate actif, son role dans la formation des esters sulfuriques de natures diverses, ainsi que sa participation eventuelle comme intermediaire au cours de la reduction du sulfate. On decrit aussi un procede de preparation du systeme biologique, generateur du sulfate actif et une methode de synthese chimique. (auteur)

  5. METABOLISM OF SULFATE-REDUCING PROKARYOTES

    NARCIS (Netherlands)

    HANSEN, TA

    1994-01-01

    Dissimilatory sulfate reduction is carried out by a heterogeneous group of bacteria and archaea that occur in environments with temperatures up to 105 degrees C. As a group together they have the capacity to metabolize a wide variety of compounds ranging from hydrogen via typical organic fermentatio

  6. Sulfate-reducing bacteria in anaerobic bioreactors

    NARCIS (Netherlands)

    Oude Elferink, S.J.W.H.

    1998-01-01

    The treatment of industrial wastewaters containing high amounts of easily degradable organic compounds in anaerobic bioreactors is a well-established process. Similarly, wastewaters which in addition to organic compounds also contain sulfate can be treated in this way. For a long time, the

  7. Plasmin Regulation through Allosteric, Sulfated, Small Molecules

    Directory of Open Access Journals (Sweden)

    Rami A. Al-Horani

    2015-01-01

    Full Text Available Plasmin, a key serine protease, plays a major role in clot lysis and extracellular matrix remodeling. Heparin, a natural polydisperse sulfated glycosaminoglycan, is known to allosterically modulate plasmin activity. No small allosteric inhibitor of plasmin has been discovered to date. We screened an in-house library of 55 sulfated, small glycosaminoglycan mimetics based on nine distinct scaffolds and varying number and positions of sulfate groups to discover several promising hits. Of these, a pentasulfated flavonoid-quinazolinone dimer 32 was found to be the most potent sulfated small inhibitor of plasmin (IC50 = 45 μM, efficacy = 100%. Michaelis-Menten kinetic studies revealed an allosteric inhibition of plasmin by these inhibitors. Studies also indicated that the most potent inhibitors are selective for plasmin over thrombin and factor Xa, two serine proteases in coagulation cascade. Interestingly, different inhibitors exhibited different levels of efficacy (40%–100%, an observation alluding to the unique advantage offered by an allosteric process. Overall, our work presents the first small, synthetic allosteric plasmin inhibitors for further rational design.

  8. Sulfate reducing potential in an estuarine beach

    Digital Repository Service at National Institute of Oceanography (India)

    LokaBharathi, P.A.; Chandramohan, D.

    Sulfate reducing bacteria (SRB) and their activity (SRA) together with total anaerobic and aerobic bacterial flora were estimated during July 1982-April 1983 and July-August 1984 from 1, 3 and 5 cm depths using core samples. The average number (no...

  9. Sulfate-reducing bacteria in anaerobic bioreactors.

    NARCIS (Netherlands)

    Oude Elferink, S.J.W.H.

    1998-01-01

    The treatment of industrial wastewaters containing high amounts of easily degradable organic compounds in anaerobic bioreactors is a well-established process. Similarly, wastewaters which in addition to organic compounds also contain sulfate can be treated in this way. For a long time, the occurrenc

  10. Sulfate transport in Penicillium chrysogenum plasma membranes

    NARCIS (Netherlands)

    Hillenga, Dirk J.; Versantvoort, Hanneke J.M.; Driessen, Arnold J.M.; Konings, Wil N.

    1996-01-01

    Transport studies with Penicillium chrysogenum plasma membranes fused with cytochrome c oxidase liposomes demonstrate that sulfate uptake is driven by the transmembrane pH gradient and not by the transmembrane electrical potential. Ca2+ and other divalent cations are not required. It is concluded th

  11. Mechanisms and Effectivity of Sulfate Reducing Bioreactors ...

    Science.gov (United States)

    Mining-influenced water (MIW) is the main environmental challenges associated with the mining industry. Passive MIW remediation can be achieved through microbial activity in sulfate-reducing bioreactors (SRBRs), but their actual removal rates depend on different factors, one of which is the substrate composition. Chitinous materials have demonstrated high metal removal rates, particularly for the two recalcitrant MIW contaminants Zn and Mn, but their removal mechanisms need further study. We studied Cd, Fe, Zn, and Mn removal in bioactive and abiotic SRBRs to elucidate the metal removal mechanisms and the differences in metal and sulfate removal rates using a chitinous material as substrate. We found that sulfate-reducing bacteria are effective in increasing metal and sulfate removal rates and duration of operation in SRBRs, and that the main mechanism involved was metal precipitation as sulfides. The solid residues provided evidence of the presence of sulfides in the bioactive column, more specifically ZnS, according to XPS analysis. The feasibility of passive treatments with a chitinous substrate could be an important option for MIW remediation. Mining influenced water (MIW) remediation is still one of the top priorities for the agency because it addresses the most important environmental problem associated with the mining industry and that affects thousands of communities in the U.S. and worldwide. In this paper, the MIW bioremediation mechanisms are studied

  12. Lung injury in dimethyl sulfate poisoning

    Energy Technology Data Exchange (ETDEWEB)

    Ip, M.; Wong, K.L.; Wong, K.F.; So, S.Y.

    1989-02-01

    Two manual laborers were exposed to dimethyl sulfate during work and sustained mucosal injury to the eyes and respiratory tract. In one of them, noncardiogenic pulmonary edema occurred and improved with high-dose methylprednisolone. On follow-up for 10 months, this patient developed persistent productive cough with no evidence of bronchiectasis or bronchial hyperreactivity.

  13. Intravenous magnesium sulfate therapy in severe asthma

    Directory of Open Access Journals (Sweden)

    Mohd. Al-Ajmi

    2007-01-01

    Full Text Available A 22-year-old female, known asthmatic since seven years, developed severe bronchospasm in the preop-erative period. Bronchospasm remained unresponsive to the inhaled beta-agonist plus anticholinergic, IV ami-nophylline and hydrocortisone but responded quickly with magnesium sulfate® ( PSI, KSA infusion 1.25gm in 100ml normal saline over 20 minutes and another 1.25 gm over next 30 minutes as the initial infusion showed improvement in her clinical symptoms. Within half an hour of administering the 1st infusion of magnesium sulfate (1.25 gm the respiratory rate started reducing, rhonchi became less, SpO 2 came upto 92% and re-mained always above 90%. Encouraged by this result IV magnesium sulfate 2.5 gm in 500 ml normal saline was infused over next 24 hours along with alternate salbutamol and ipratropium nebulization every 6 hourly. With this treatment regimen the patient became asymptomatic within next 24 hours with normal clinical parameters and FEV 1 value. Hence it may be concluded that IV magnesium sulfate can be considered for patients with acute severe asthma who do not respond to standard therapeutic medications.

  14. Galactose 6-sulfate sulfatase activity in Morquio syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Yutaka, T.; Okada, S.; Kato, T.; Inui, K.; Yabuuhi, H. (Osaka Univ. (Japan). Faculty of Medicine)

    1982-07-01

    The authors have prepared a new substrate, o-..beta..-D-sulfo-galactosyl-(1-4)-..beta..-D-6-sulfo-2-acetamido-2-deoxyglucosyl-(1-4)-D-(1-/sup 3/H)galactitol, from shark cartilage keratan sulfate, for the assay of galactose 6-sulfate sulfatase activity. Using this substrate, they found there was a striking deficiency of galactose 6-sulfate sulfatase activity, in addition to the known deficiency of N-acetylgalactosamine 6-sulfate sulfatase, in the cultured skin fibroblasts of patients with Morquio syndrome. Their results could be explained by the hypothesis that accumulation of keratan sulfate and chondroitin 6-sulfate in Morquio syndrome is due to a deficiency of galactose 6-sulfate sulfatase and N-acetylgalactosamine 6-sulfate sulfatase activity, which are necessary for the degradation of these two mucopolysaccharides.

  15. Comparative Evaluation of Ankaferd Blood Stopper, Ferric Sulfate ...

    African Journals Online (AJOL)

    2016-07-24

    Jul 24, 2016 ... ferric sulfate (FS) as pulpotomy agent in primary teeth. Settings and Design: ... sulfate (FS), calcium hydroxide (CH), and mineral trioxide aggregate ..... internal root resorption may remain stable or may be repaired with hard ...

  16. Bacterial transport of sulfate, molybdate, and related oxyanions.

    Science.gov (United States)

    Aguilar-Barajas, Esther; Díaz-Pérez, César; Ramírez-Díaz, Martha I; Riveros-Rosas, Héctor; Cervantes, Carlos

    2011-08-01

    Sulfur is an essential element for microorganisms and it can be obtained from varied compounds, sulfate being the preferred source. The first step for sulfate assimilation, sulfate uptake, has been studied in several bacterial species. This article reviews the properties of different bacterial (and archaeal) transporters for sulfate, molybdate, and related oxyanions. Sulfate uptake is carried out by sulfate permeases that belong to the SulT (CysPTWA), SulP, CysP/(PiT), and CysZ families. The oxyanions molybdate, tungstate, selenate and chromate are structurally related to sulfate. Molybdate is transported mainly by the high-affinity ModABC system and tungstate by the TupABC and WtpABC systems. CysPTWA, ModABC, TupABC, and WtpABC are homologous ATP-binding cassette (ABC)-type transporters with similar organization and properties. Uptake of selenate and chromate oxyanions occurs mainly through sulfate permeases.

  17. Pregnenolone Sulfate: From Steroid Metabolite to TRP Channel Ligand

    Directory of Open Access Journals (Sweden)

    Christian Harteneck

    2013-09-01

    Full Text Available Pregnenolone sulfate is a steroid metabolite with a plethora of actions and functions. As a neurosteroid, pregnenolone sulfate modulates a variety of ion channels, transporters, and enzymes. Interestingly, as a sulfated steroid, pregnenolone sulfate is not the final- or waste-product of pregnenolone being sulfated via a phase II metabolism reaction and renally excreted, as one would presume from the pharmacology textbook knowledge. Pregnenolone sulfate is also the source and thereby the starting point for subsequent steroid synthesis pathways. Most recently, pregnenolone sulfate has been functionally “upgraded” from modulator of ion channels to an activating ion channel ligand. This review will focus on molecular aspects of the neurosteroid, pregnenolone sulfate, its metabolism, concentrations in serum and tissues and last not least will summarize the functional data.

  18. The Importance of Sulfate Adenylyl Transferase in S and O Fractionation by Sulfate Reducing Bacteria

    Science.gov (United States)

    Smith, D. A.; Johnston, D. T.; Bradley, A. S.

    2016-12-01

    Microbial sulfate reduction (MSR) is critical to the oxidation of organic matter in modern and ancient oceans, and plays an important role in regulating the redox state of the Earth's surface. The sulfur and oxygen isotopic composition of seawater sulfate and of sulfate minerals reflect the biogeochemical processes that cycle sulfur, of which MSR is among the most important. MSR is a multi-enzymatic reaction network that partitions the isotopes of sulfur and oxygen as a consequence of both the flux of sulfate through this biochemical network and the fractionation imposed by each individual enzyme. MSR affects the δ18O of residual, extracellular sulfate mainly by the equilibration of the MSR intermediate sulfite with extracellular water (Antler et al., 2013 GCA, Wankel et al., 2013 Geobiol). A series of oxidative and exchange reactions catalyzed by APS reductase (APSr), sulfate adenylyl transferase (Sat), and sulfate transporters promote the conversion of water-equilibrated intracellular sulfite to extracellular sulfate. The flux of sulfoxy anions via these proteins will be, at least in part, dependent on the activity of these enzymes. To test this, we examined sulfur and oxygen isotope fractionation in genetically engineered mutants of the sulfate reducing bacterium Desulfovibrio vulgaris Hildenborough (DvH). In these mutants, the activity of Sat has been artificially increased by perturbing the (i) transcriptional repressor Rex and (ii) its binding site upstream of the gene encoding Sat (Christensen et al., 2015 J. Bacteriol). It was predicted that this would minimize the back reaction of Sat, enhance the intracellular pool of APS, and minimize the equilibration between sulfite and adenosine monophosphate (AMP). Both mutants, along with the wild type DvH were grown in batch culture made with water enriched in 18O. Samples were collected throughout batch growth, and we report the evolution of the S and O isotopic composition of sulfate, and of the S isotopic

  19. Sources of sulfate supporting anaerobic metabolism in a contaminated aquifer

    Science.gov (United States)

    Ulrich, G.A.; Breit, G.N.; Cozzarelli, I.M.; Suflita, J.M.

    2003-01-01

    Field and laboratory techniques were used to identify the biogeochemical factors affecting sulfate reduction in a shallow, unconsolidated alluvial aquifer contaminated with landfill leachate. Depth profiles of 35S-sulfate reduction rates in aquifer sediments were positively correlated with the concentration of dissolved sulfate. Manipulation of the sulfate concentration in samples revealed a Michaelis-Menten-like relationship with an apparent Km and Vmax of approximately 80 and 0.83 ??M SO4-2??day-1, respectively. The concentration of sulfate in the core of the leachate plume was well below 20 ??M and coincided with very low reduction rates. Thus, the concentration and availability of this anion could limit in situ sulfate-reducing activity. Three sulfate sources were identified, including iron sulfide oxidation, barite dissolution, and advective flux of sulfate. The relative importance of these sources varied with depth in the alluvium. The relatively high concentration of dissolved sulfate at the water table is attributed to the microbial oxidation of iron sulfides in response to fluctuations of the water table. At intermediate depths, barite dissolves in undersaturated pore water containing relatively high concentrations of dissolved barium (???100 ??M) and low concentrations of sulfate. Dissolution is consistent with the surface texture of detrital barite grains in contact with leachate. Laboratory incubations of unamended and barite-amended aquifer slurries supported the field observation of increasing concentrations of barium in solution when sulfate reached low levels. At a deeper highly permeable interval just above the confining bottom layer of the aquifer, sulfate reduction rates were markedly higher than rates at intermediate depths. Sulfate is supplied to this deeper zone by advection of uncontaminated groundwater beneath the landfill. The measured rates of sulfate reduction in the aquifer also correlated with the abundance of accumulated iron sulfide

  20. 21 CFR 522.1484 - Neomycin sulfate sterile solution.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Neomycin sulfate sterile solution. 522.1484... § 522.1484 Neomycin sulfate sterile solution. (a) Specifications. Each milliliter of sterile aqueous solution contains 50 milligrams of neomycin sulfate (equivalent to 35 milligrams of neomycin base).1...

  1. 21 CFR 524.1484a - Neomycin sulfate ophthalmic ointment.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Neomycin sulfate ophthalmic ointment. 524.1484a... § 524.1484a Neomycin sulfate ophthalmic ointment. (a) Specifications. Each gram of the ointment contains 5 milligrams of neomycin sulfate equivalent in activity to 3.5 milligrams of neomycin base....

  2. Nanocrystalline cellulose with various contents of sulfate groups.

    Science.gov (United States)

    Voronova, M I; Surov, O V; Zakharov, A G

    2013-10-15

    Properties of films derived from aqueous nanocrystalline cellulose dispersions by water evaporation depend on concentration of sulfate groups. Namely type of thermodestruction and surface morphology change as a function of contents of sulfate groups. Surface roughness increases and water adsorption enhances with increasing sulfate groups content particularly at high relative pressure.

  3. De Novo Sequencing of Complex Mixtures of Heparan Sulfate Oligosaccharides

    NARCIS (Netherlands)

    Huang, Rongrong; Zong, Chengli; Venot, Andre; Chiu, Yulun; Zhou, Dandan; Boons, Geert-Jan; Sharp, Joshua S

    2016-01-01

    Here, we describe the first sequencing method of a complex mixture of heparan sulfate tetrasaccharides by LC-MS/MS. Heparin and heparan sulfate (HS) are linear polysaccharides that are modified in a complex manner by N- and O-sulfation, N-acetylation, and epimerization of the uronic acid. Heparin an

  4. Thermophilic Sulfate-Reducing Bacteria in Cold Marine Sediment

    DEFF Research Database (Denmark)

    ISAKSEN, MF; BAK, F.; JØRGENSEN, BB

    1994-01-01

    C to search for presence of psychrophilic, mesophilic and thermophilic sulfate-reducing bacteria. Detectable activity was initially only in the mesophilic range, but after a lag phase sulfate reduction by thermophilic sulfate-reducing bacteria were observed. No distinct activity of psychrophilic...

  5. Acid Sulfate Alteration in Gusev Crater, Mars

    Science.gov (United States)

    Morris, R. V.; Ming, D. W.; Catalano, J. G.

    2016-01-01

    The Mars Exploration Rover (MER) Spirit landed on the Gusev Crater plains west of the Columbia Hills in January, 2004, during the Martian summer (sol 0; sol = 1 Martian day = 24 hr 40 min). Spirit explored the Columbia Hills of Gusev Crater in the vicinity of Home Plate at the onset on its second winter (sol approximately 900) until the onset of its fourth winter (sol approximately 2170). At that time, Spirit became mired in a deposit of fined-grained and sulfate-rich soil with dust-covered solar panels and unfavorable pointing of the solar arrays toward the sun. Spirit has not communicated with the Earth since sol 2210 (January, 2011). Like its twin rover Opportunity, which landed on the opposite side of Mars at Meridiani Planum, Spirit has an Alpha Particle X-Ray Spectrometer (APXS) instrument for chemical analyses and a Moessbauer spectrometer (MB) for measurement of iron redox state, mineralogical speciation, and quantitative distribution among oxidation (Fe(3+)/sigma Fe) and coordination (octahedral versus tetrahedral) states and mineralogical speciation (e.g., olivine, pyroxene, ilmenite, carbonate, and sulfate). The concentration of SO3 in Gusev rocks and soils varies from approximately 1 to approximately 34 wt%. Because the APXS instrument does not detect low atomic number elements (e.g., H and C), major-element oxide concentrations are normalized to sum to 100 wt%, i.e., contributions of H2O, CO2, NO2, etc. to the bulk composition care not considered. The majority of Gusev samples have approximately 6 plus or minus 5 wt% SO3, but there is a group of samples with high SO3 concentrations (approximately 30 wt%) and high total iron concentrations (approximately 20 wt%). There is also a group with low total Fe and SO3 concentrations that is also characterized by high SiO2 concentrations (greater than 70 wt%). The trend labeled "Basaltic Soil" is interpreted as mixtures in variable proportions between unaltered igneous material and oxidized and SO3-rich basaltic

  6. Introduction of sulfate groups on poly(ethylene) surfaces by argon plasma immobilization of sodium alkyl sulfates

    NARCIS (Netherlands)

    Lens, J.P.; Terlingen, J.G.A.; Engbers, G.H.M.; Feijen, J.

    1998-01-01

    Sulfate groups were introduced at the surface of poly(ethylene) (PE) samples. This was accomplished by immobilizing a precoated layer of either sodium 10-undecene sulfate (S11(:)) or sodium dodecane sulfate (SDS) on the polymeric surface by means of an argon plasma treatment. For this purpose, S11(:

  7. ELECTRON DETACHMENT DISSOCIATION OF SYNTHETIC HEPARAN SULFATE GLYCOSAMINOGLYCAN TETRASACCHARIDES VARYING IN DEGREE OF SULFATION AND HEXURONIC ACID STEREOCHEMISTRY.

    Science.gov (United States)

    Leach, Franklin E; Arungundram, Sailaja; Al-Mafraji, Kanar; Venot, Andre; Boons, Geert-Jan; Amster, I Jonathan

    2012-12-15

    Glycosaminoglycan (GAG) carbohydrates provide a challenging analytical target for structural determination due to their polydisperse nature, non-template biosynthesis, and labile sulfate modifications. The resultant structures, although heterogeneous, contain domains which indicate a sulfation pattern or code that correlates to specific function. Mass spectrometry, in particular electron detachment dissociation Fourier transform ion cyclotron resonance (EDD FT-ICR MS), provides a highly sensitive platform for GAG structural analysis by providing cross-ring cleavages for sulfation location and product ions specific to hexuronic acid stereochemistry. To investigate the effect of sulfation pattern and variations in stereochemistry on EDD spectra, a series of synthetic heparan sulfate (HS) tetrasaccharides are examined. Whereas previous studies have focused on lowly sulfated compounds (0.5-1 sulfate groups per disaccharide), the current work extends the application of EDD to more highly sulfated tetrasaccharides (1-2 sulfate groups per disaccharide) and presents the first EDD of a tetrasaccharide containing a sulfated hexuronic acid. For these more highly sulfated HS oligomers, alternative strategies are shown to be effective for extracting full structural details. These strategies inlcude sodium cation replacement of protons, for determining the sites of sulfation, and desulfation of the oligosaccharides for the generation of product ions for assigning uronic acid stereochemistry.

  8. Prognostic significance of highly sulfated chondroitin sulfates in ovarian cancer defined by the single chain antibody GD3A11

    NARCIS (Netherlands)

    Steen, S.C.H.A. van der; Tilborg, A.G. van; Vallen, M.J.E.; Bulten, J.; Kuppevelt, T.H. van; Massuger, L.F.

    2016-01-01

    OBJECTIVE: The extracellular matrix (ECM) of ovarian cancer may provide a number of potential biomarkers. Chondroitin sulfate (CS), a class of sulfated polysaccharides, is abundantly present in the ECM of ovarian cancer. Structural alterations of CS chains (i.e. sulfation pattern) have been demonstr

  9. High rates of sulfate reduction in a low-sulfate hot spring microbial mat are driven by a low level of diversity of sulfate-respiring microorganisms

    DEFF Research Database (Denmark)

    Dillon, Jesse G; Fishbain, Susan; Miller, Scott R

    2007-01-01

    The importance of sulfate respiration in the microbial mat found in the low-sulfate thermal outflow of Mushroom Spring in Yellowstone National Park was evaluated using a combination of molecular, microelectrode, and radiotracer studies. Despite very low sulfate concentrations, this mat community...... was shown to sustain a highly active sulfur cycle. The highest rates of sulfate respiration were measured close to the surface of the mat late in the day when photosynthetic oxygen production ceased and were associated with a Thermodesulfovibrio-like population. Reduced activity at greater depths...... was correlated with novel populations of sulfate-reducing microorganisms, unrelated to characterized species, and most likely due to both sulfate and carbon limitation....

  10. Effect of magnetic field on the crystallization of zinc sulfate

    Directory of Open Access Journals (Sweden)

    Freitas A. M. B.

    2000-01-01

    Full Text Available The effect of magnetic field on the crystallization of diamagnetic zinc sulfate was investigated in a series of controlled batch cooling experiments. Zinc sulfate solutions were exposed to magnetic fields of different intensities, up to a maximum of 0.7T. A clear influence of magnetic field on the following zinc sulfate crystallization parameters was found: an increase in saturation temperature, a decrease in metastable zone width, and an increase in growth rate and average crystal size. These effects were observed for the diamagnetic zinc sulfate, but not in similar, previously reported experiments for paramagnetic copper sulfate.

  11. Sulfate and acid resistant concrete and mortar

    Science.gov (United States)

    Liskowitz, John W.; Wecharatana, Methi; Jaturapitakkul, Chai; Cerkanowicz, deceased, Anthony E.

    1998-01-01

    The present invention relates to concrete, mortar and other hardenable mixtures comprising cement and fly ash for use in construction and other applications, which hardenable mixtures demonstrate significant levels of acid and sulfate resistance while maintaining acceptable compressive strength properties. The acid and sulfate hardenable mixtures of the invention containing fly ash comprise cementitious materials and a fine aggregate. The cementitous materials may comprise fly ash as well as cement. The fine aggregate may comprise fly ash as well as sand. The total amount of fly ash in the hardenable mixture ranges from about 60% to about 120% of the total amount of cement, by weight, whether the fly ash is included as a cementious material, fine aggregate, or an additive, or any combination of the foregoing. In specific examples, mortar containing 50% fly ash and 50% cement in cementitious materials demonstrated superior properties of corrosion resistance.

  12. Effects of sulfate chitosan derivatives on nonalcoholic fatty liver disease

    Science.gov (United States)

    Yu, Mingming; Wang, Yuanhong; Jiang, Tingfu; Lv, Zhihua

    2014-06-01

    Sulfate chitosan derivatives have good solubility and therapeutic effect on the cell model of NAFLD. The aim of this study was to examine the therapeutic effect of sulfate chitosan derivatives on NAFLD. The male Wistar rats were orally fed high fat emulsion and received sulfate chitosan derivatives for 5 weeks to determine the pre-treatment effect of sulfate chitosan derivatives on NAFLD. To evaluate the therapeutic effect of sulfate chitosan derivatives on NAFLD, the rats were orally fed with high concentration emulsion for 5 weeks, followed by sulfate chitosan derivatives for 3 weeks. Histological analysis and biomedical assays showed that sulfate chitosan derivatives can dramatically prevent the development of hepatic steatosis in hepatocyte cells. In animal studies, pre-treatment and treatment with sulfate chitosan derivatives significantly protected against hepatic steatohepatitis induced by high fat diet according to histological analysis. Furthermore, increased TC, ALT, MDA, and LEP in NAFLD were significantly ameliorated by pre-treatment and treatment with sulfate chitosan derivatives. Furthermore, increased TG, AST, and TNF-α in NAFLD were significantly ameliorated by treatment with sulfate chitosan derivatives. Sulfate chitosan derivatives have good pre-treatment and therapeutic effect on NAFLD.

  13. Effects of Sulfate Chitosan Derivatives on Nonalcoholic Fatty Liver Disease

    Institute of Scientific and Technical Information of China (English)

    YU Mingming; WANG Yuanhong; JIANG Tingfu; LV Zhihua

    2014-01-01

    Sulfate chitosan derivatives have good solubility and therapeutic effect on the cell model of NAFLD. The aim of this study was to examine the therapeutic effect of sulfate chitosan derivatives on NAFLD. The male Wistar rats were orally fed high fat emulsion and received sulfate chitosan derivatives for 5 weeks to determine the pre-treatment effect of sulfate chitosan derivatives on NAFLD. To evaluate the therapeutic effect of sulfate chitosan derivatives on NAFLD, the rats were orally fed with high concentra-tion emulsion for 5 weeks, followed by sulfate chitosan derivatives for 3 weeks. Histological analysis and biomedical assays showed that sulfate chitosan derivatives can dramatically prevent the development of hepatic steatosis in hepatocyte cells. In animal studies, pre-treatment and treatment with sulfate chitosan derivatives significantly protected against hepatic steatohepatitis induced by high fat diet according to histological analysis. Furthermore, increased TC, ALT, MDA, and LEP in NAFLD were significantly amelio-rated by pre-treatment and treatment with sulfate chitosan derivatives. Furthermore, increased TG, AST, and TNF-α in NAFLD were significantly ameliorated by treatment with sulfate chitosan derivatives. Sulfate chitosan derivatives have good pre-treatment and therapeutic effect on NAFLD.

  14. The Importance of Heparan Sulfate in Herpesvirus Infection

    Institute of Scientific and Technical Information of China (English)

    Christopher D.O'Donnell; Deepak Shukla

    2008-01-01

    Herpes simplex virus type-1 (HSV-1) is one of many pathogens that use the cell surface glycosaminoglycan heparan sulfate as a receptor.Heparan sulfate is highly expressed on the surface and extracellular matrix of virtually all cell types making it an ideal receptor.Heparan sulfate interacts with HSV-1 envelope glycoproteins gB and gC during the initial attachment step during HSV-1 entry.In addition,a modified form of heparan sulfate,known as 3-O-sulfated heparan sulfate,interacts with HSV-1 gD to induce fusion between the viral envelope and host cell membrane.The 3-O-sulfation of heparan sulfate is a rare modification which occurs during the biosynthesis of heparan sulfate that is carded out by a family of enzymes known as 3-O-sulfotransferases.Due to its involvement in multiple steps of the infection process,heparan sulfate has been a prime target for the development of agents to inhibit HSV entry.Understanding how heparan sulfate functions during HSV-1 infection may not only be critical for inhibiting infection by this virus,but it may also be crucial in the fight against many other pathogens as well.

  15. Sulfate was a trace constituent of Archean seawater

    DEFF Research Database (Denmark)

    Crowe, Sean Andrew; Paris, Guillaume; Katsev, Sergei

    2014-01-01

    In the low-oxygen Archean world (>2400 million years ago), seawater sulfate concentrations were much lower than today, yet open questions frustrate the translation of modern measurements of sulfur isotope fractionations into estimates of Archean seawater sulfate concentrations. In the water column...... of Lake Matano, Indonesia, a low-sulfate analog for the Archean ocean, we find large (>20 per mil) sulfur isotope fractionations between sulfate and sulfide, but the underlying sediment sulfides preserve a muted range of delta S-34 values. Using models informed by sulfur cycling in Lake Matano, we infer...... Archean seawater sulfate concentrations of less than 2.5 micromolar. At these low concentrations, marine sulfate residence times were likely 10(3) to 10(4) years, and sulfate scarcity would have shaped early global biogeochemical cycles, possibly restricting biological productivity in Archean oceans....

  16. Thermophilic Sulfate-Reducing Bacteria in Cold Marine Sediment

    DEFF Research Database (Denmark)

    ISAKSEN, MF; BAK, F.; JØRGENSEN, BB

    1994-01-01

    Sulfate reduction was measured with the (SO42-)-S-35-tracer technique in slurries of sediment from Aarhus Bay, Denmark, where seasonal temperatures range from 0 degrees to 15 degrees C. The incubations were made at temperatures from 0 degrees C to 80 degrees C in temperature increments of 2 degrees...... C to search for presence of psychrophilic, mesophilic and thermophilic sulfate-reducing bacteria. Detectable activity was initially only in the mesophilic range, but after a lag phase sulfate reduction by thermophilic sulfate-reducing bacteria were observed. No distinct activity of psychrophilic...... sulfate-reducing bacteria was detected. Time course experiments showed constant sulfate reduction rates at 4 degrees C and 30 degrees C, whereas the activity at 60 degrees C increased exponentially after a lag period of one day. Thermophilic, endospore-forming sulfate-reducing bacteria, designated strain...

  17. Studies on the binding of amylopectin sulfate with gastric mucin.

    Science.gov (United States)

    Kim, Y S; Bella, A; Whitehead, J S; Isaacs, R; Remer, L

    1975-07-01

    Amylopectin sulfate, a sulfated polysaccharide that has an antipeptic property, was examined for its ability to bind gastric mucins. After chemically cross-linking the amylopectin sulfate into an insoluble gel, its binding with mucins isolated from antral and fundic mucosa of canine stomachs was studied with chromatography. A component present in both mucin fractions bound to the amylopectin sulfate gel below pH 4.5. This binding was reversible, and the complex dissociated above pH 5. Similar binding properties were found with soluble amylopectin sulfate. The component of the mucine which bound to amylopectin sulfate differed from the one which did not bind in its electrophoretic mobility and in its higher proportion of basic amino acids and a lower hexosamine, serine, and threonine content. This study suggests that amylopectin sulfate may bind to gastric mucins only under conditions of low pH.

  18. Nickel hydroxide precipitation from aqueous sulfate media

    Science.gov (United States)

    Sist, Cinziana; Demopoulos, George P.

    2003-08-01

    Hydrometallurgical processing of laterite ores constitutes a major industrial and R&D activity in extractive metallurgy. In some of the process flowsheets, nickel hydroxide precipitation is incorporated. For these operations, the optimization of nickel hydroxide precipitation is important to assure efficiency and product quality. The main objective of this investigation was to study and improve the precipitation characteristics of Ni(OH)2 in a sulfate system using supersaturation controlled precipitation.

  19. Engineering sulfotransferases to modify heparan sulfate

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Ding; Moon, Andrea F.; Song, Danyin; Pedersen, Lars C.; Liu, Jian (NIH); (UNC)

    2008-03-19

    The biosynthesis of heparan sulfate (HS) involves an array of specialized sulfotransferases. Here, we present a study aimed at engineering the substrate specificity of different HS 3-O-sulfotransferase isoforms. Based on the crystal structures, we identified a pair of amino acid residues responsible for selecting the substrates. Mutations of these residues altered the substrate specificities. Our results demonstrate the feasibility of tailoring the specificity of sulfotransferases to modify HS with desired functions.

  20. Sulfation and Cation Effects on the Conformational Properties of the Glycan Backbone of Chondroitin Sulfate Disaccharides

    Science.gov (United States)

    Faller, Christina E.; Guvench, Olgun

    2015-01-01

    Chondroitin sulfate (CS) is one of several glycosaminoglycans that are major components of proteoglycans. A linear polymer consisting of repeats of the disaccharide -4GlcAβ1-3GalNAcβ1-, CS undergoes differential sulfation resulting in five unique sulfation patterns. Because of the dimer repeat, the CS glycosidic “backbone” has two distinct sets of conformational degrees of freedom defined by pairs of dihedral angles: (ϕ1, ψ1) about the β1-3 glycosidic linkage and (ϕ2, ψ2) about the β1-4 glycosidic linkage. Differential sulfation and the possibility of cation binding, combined with the conformational flexibility and biological diversity of CS, complicate experimental efforts to understand CS three-dimensional structures at atomic resolution. Therefore, all-atom explicit-solvent molecular dynamics simulations with Adaptive Biasing Force sampling of the CS backbone were applied to obtain high resolution, high precision free energies of CS disaccharides as a function of all possible backbone geometries. All ten disaccharides (β1-3 vs. β1-4 linkage x five different sulfation patterns) were studied; additionally, ion effects were investigated by considering each disaccharide in the presence of either neutralizing sodium or calcium cations. GlcAβ1-3GalNAc disaccharides have a single, broad, thermodynamically important free-energy minimum whereas GalNAcβ1-4GlcA disaccharides have two such minima. Calcium cations but not sodium cations bind to the disaccharides, and binding is primarily to the GlcA –COO− moiety as opposed to sulfate groups. This binding alters the glycan backbone thermodynamics in instances where a calcium cation bound to –COO− can act to bridge and stabilize an interaction with an adjacent sulfate group, whereas, in the absence of this cation, the proximity of a sulfate group to –COO− results in two like charges being both desolvated and placed adjacent to each other and is found to be destabilizing. In addition to providing

  1. Conformation of sulfated galactan and sulfated fucan in aqueous solutions: implications to their anticoagulant activities.

    Science.gov (United States)

    Becker, Camila F; Guimarães, Jorge A; Mourão, Paulo A S; Verli, Hugo

    2007-07-01

    The discovery of sulfated galactans and sulfated fucans in marine invertebrates with simple and ordered structures opened new perspectives to investigate the biological activity of these molecules and to determine whether different structures confer high affinity for a particular protein. We undertook a conformational analysis of a 2-sulfated, 3-linked alpha-L-galactan and of a alpha-L-fucan with similar structure. Through comparison between theoretical and NMR derived coupling constants, we observed that the pyranose rings are predominantly in the (1)C(4) conformation in these polysaccharides. Additionally, the geometry of the glycosidic linkages was determined based on force field calculations, indicating that the two polysaccharides have similar conformations in solution. Since the sulfated alpha-L-galactan, but not the alpha-L-fucan potentiates antithrombin (AT) inhibition of thrombin, the solution conformations of the compounds were docked into AT and the complexes obtained were refined through molecular dynamics calculations. The obtained results indicates extremely different orientations for the two polysaccharides, which well correlates and explain their distinct anticoagulant activities. Finally, the molecular mechanism of a selective 2-desulfation reaction, observed among sulfated fucans, was explained as a consequence of an intramolecular hydrogen bond capable of assisting in the removal of the charged group.

  2. Effect of Systemic Lupus Erythematosus on some Biochemical Parameters in Female Patients

    OpenAIRE

    Eman G.E Helal*, Medhat El- Shafaey**, Hala Rahoma

    2004-01-01

    It has been noticed that there is an increase in the number of women suffering from SLE. Most studies confirmed that serum DHEA (dehydroepiandrosterone) and DHEA sulphate are lower among patients with SLE than among controls even- during phases of inactive disease so we performed this study to detect the level of DHEA-S in the female patients with SLE. The overall results confirm that DHEA treatment was well- tolerated, significantly reduced the number of SLE flares, and improved patient's gl...

  3. DHEA metabolites activate estrogen receptors alpha and beta

    OpenAIRE

    Michael Miller, Kristy K.; AL-RAYYAN, NUMAN; Ivanova, Margarita M.; Mattingly, Kathleen A.; Ripp, Sharon L.; Klinge, Carolyn M; Prough, Russell A.

    2012-01-01

    Dehydroepiandrosterone (DHEA) levels were reported to associate with increased breast cancer risk in postmenopausal women, but some carcinogen-induced rat mammary tumor studies question this claim. The purpose of this study was to determine how DHEA and its metabolites affect estrogen receptors α or β (ERα or ERβ) -regulated gene transcription and cell proliferation. In transiently transfected HEK-293 cells, androstenediol, DHEA, and DHEA-S activated ERα. In ERβ transfected HepG2 cells, andro...

  4. Heritability and clinical determinants of serum indoxyl sulfate and p-cresyl sulfate, candidate biomarkers of the human microbiome enterotype.

    Directory of Open Access Journals (Sweden)

    Liesbeth Viaene

    Full Text Available BACKGROUND: Indoxyl sulfate and p-cresyl sulfate are unique microbial co-metabolites. Both co-metabolites have been involved in the pathogenesis of accelerated cardiovascular disease and renal disease progression. Available evidence suggests that indoxyl sulfate and p-cresyl sulfate may be considered candidate biomarkers of the human enterotype and may help to explain the link between diet and cardiovascular disease burden. OBJECTIVE AND DESIGN: Information on clinical determinants and heritability of indoxyl sulfate and p-cresyl sulfate serum is non-existing. To clarify this issue, the authors determined serum levels of indoxyl sulfate and p-cresyl sulfate in 773 individuals, recruited in the frame of the Flemish Study on Environment, Genes and Health Outcomes (FLEMENGHO study. RESULTS: Serum levels of indoxyl sulfate and p-cresyl sulfate amounted to 3.1 (2.4-4.3 and 13.0 (7.4-21.5 μM, respectively. Regression analysis identified renal function, age and sex as independent determinants of both co-metabolites. Both serum indoxyl sulfate (h2 = 0.17 and p-cresyl sulfate (h2 = 0.18 concentrations showed moderate but significant heritability after adjustment for covariables, with significant genetic and environmental correlations for both co-metabolites. LIMITATIONS: Family studies cannot provide conclusive evidence for a genetic contribution, as confounding by shared environmental effects can never be excluded. CONCLUSIONS: The heritability of indoxyl sulfate and p-cresyl sulfate is moderate. Besides genetic host factors and environmental factors, also renal function, sex and age influence the serum levels of these co-metabolites.

  5. Purity determination of amphotericin B, colistin sulfate and tobramycin sulfate in a hydrophilic suspension by HPLC.

    Science.gov (United States)

    Pfeifer, Corina; Fassauer, Georg; Gerecke, Hagen; Jira, Thomas; Remane, Yvonne; Frontini, Roberto; Byrne, Jonathan; Reinhardt, Robert

    2015-05-15

    A suspension comprising of the three antibiotic substances amphotericin B, colistin sulfate and tobramycin sulfate is often used in clinical practice for the selective decontamination of the digestive tract of patients in intensive care. Since no detailed procedures, specifications or stability data are available for manufacturing this suspension, there may be discrepancies regarding formulation and stability of suspensions prepared in different pharmacies. The aim of this work is to develop a standardized formulation and to determine its stability under defined storage conditions. This would help guarantee that all patients receive the same preparation, therefore ensuring similar efficacy and improved safety. The first step in this process is to develop the required analytical tools to measure the content and purity of the drug substances in this complex mixture. In this paper, the development and validation of these tools as well as the development of the drug suspension formulation is described. The formulation comprises of Ampho-Moronal(®)-Suspension (Dermapharm) and a buffered, preservated aqueous solution of colistin sulfate and tobramycin sulfate. Two simple, well established high-performance liquid chromatography (HPLC) methods in the European Pharmacopoeia (EP) for impurity profiling of the two active ingredients amphotericin B and colistin sulfate were combined with a newly developed sample extraction procedure for the suspension. Sufficient selectivity and stability-indicating power have been demonstrated. Additionally, a new robust routine method was developed to determine possible degradation products of tobramycin sulfate in the investigated suspension. The specificity, precision, accuracy and linearity of the analytical procedures were demonstrated. The recovery rate was in the range of 90-110%. The precision results for the calculated impurities showed variation coefficients of <10%. The calibration curves were found to be linear with correlation

  6. Sulfation pattern of fucose branches affects the anti-hyperlipidemic activities of fucosylated chondroitin sulfate.

    Science.gov (United States)

    Wu, Nian; Zhang, Yu; Ye, Xingqian; Hu, Yaqin; Ding, Tian; Chen, Shiguo

    2016-08-20

    Fucosylated chondroitin sulfates (fCSs) are glycosaminoglycans extracted from sea cucumbers, consisting of chondroitin sulfate E (CSE) backbones and sulfated fucose branches. The biological properties of fCSs could be affected by the sulfation pattern of their fucose branches. In the present study, two fCSs were isolated from sea cucumbers Isostichopus badionotus (fCS-Ib) and Pearsonothuria graeffei (fCS-Pg). Their monosaccharide compositions of glucuronic acid (GlcA), N-acetylgalactosamine (GalNAc), fucose (Fuc) and sulfate were at similar molar ratio with 1.0/0.7/0.9/3.1 for fCS-Ib and 1.0/0.8/1.5/2.6 for fCS-Pg. The two fCSs have different sulfation patterns on their fucose branches, fCS-Pg with 3,4-O-disulfation while fCS-Ib with 2,4-O-disulfation. Their antihyperlipidemic effects were compared using a high-fat high-fructose diet (HFFD)-fed C57BL/6J mice model. Both fCS-Ib and fCS-Pg had significant effects on lipid profile improvement, liver protection, blood glucose diminution and hepatic glycogen synthesis. Specifically, fCS-Pg with 3,4-O-disulfation fucose branches was more effective in reduction of blood cholesterol (TC), low density lipoprotein (LDL) and atherogenic index (AI). Our results indicate that both fCSs, especially fCS-Pg, could be used as a potential anti-hyperlipidemic drug.

  7. The preparation and antioxidant activity of glucosamine sulfate

    Institute of Scientific and Technical Information of China (English)

    XING Ronge; LIU Song; WANG Lin; CAI Shengbao; YU Huahua; FENG Jinhua; LI Pengcheng

    2009-01-01

    Glucosamine sulfate was prepared from glucosamine hydrochloride that was produced by acidic hydrolysis of chitin by ion-exchange method. Optical rotation and elemental analysis characterized the degree of its purity. In addition, the antioxidant potency of chitosan derivative-glucosamine sulfate was investigated in various established in vitro systems, such as superoxide (O(2))/hydroxyl (·OH) radicals scavenging, reducing power, iron ion chelating. The following results are obtained: first, glucosamine sulfate had pronounced scavenging effect on superoxide radical. For example the O(2) scavenging activity of glucosamine sulfate was 92.11% at 0.8 mg/mL. Second, the ·OH scavenging activity of glucosamine sulfate was also strong, and was about 50% at 3.2 mg/mL Third, the reducing power of glucosamine sulfate was more pronounced. The reducing power of glucosamine sulfate was 0.643 at 0.75 mg/mL.However, its potency for ferrous ion chelating was weak. Furthermore, except for ferrous ion chelating potency, the scavenging rate of radical and reducing power of glucosamine sulfate were concentration-dependent and increased with their increasing concentrations, but its ferrous ion chelating potency decreased with the increasing concentration. The multiple antioxidant activities of glucosamine sulfate were evidents of reducing power and superoxide/hydroxyl radicals scavenging ability. These in vitro results suggest the possibility that glucosamine sulfate could be used effectively as an ingredient in health or functional food, to alleviate oxidative stress.

  8. The preparation and antioxidant activity of glucosamine sulfate

    Science.gov (United States)

    Xing, Ronge; Liu, Song; Wang, Lin; Cai, Shengbao; Yu, Huahua; Feng, Jinhua; Li, Pengcheng

    2009-05-01

    Glucosamine sulfate was prepared from glucosamine hydrochloride that was produced by acidic hydrolysis of chitin by ion-exchange method. Optical rotation and elemental analysis characterized the degree of its purity. In addition, the antioxidant potency of chitosan derivative-glucosamine sulfate was investigated in various established in vitro systems, such as superoxide (O{2/-})/hydroxyl (·OH) radicals scavenging, reducing power, iron ion chelating. The following results are obtained: first, glucosamine sulfate had pronounced scavenging effect on superoxide radical. For example the O{2/-} scavenging activity of glucosamine sulfate was 92.11% at 0.8 mg/mL. Second, the ·OH scavenging activity of glucosamine sulfate was also strong, and was about 50% at 3.2 mg/mL. Third, the reducing power of glucosamine sulfate was more pronounced. The reducing power of glucosamine sulfate was 0.643 at 0.75 mg/mL. However, its potency for ferrous ion chelating was weak. Furthermore, except for ferrous ion chelating potency, the scavenging rate of radical and reducing power of glucosamine sulfate were concentration-dependent and increased with their increasing concentrations, but its ferrous ion chelating potency decreased with the increasing concentration. The multiple antioxidant activities of glucosamine sulfate were evidents of reducing power and superoxide/hydroxyl radicals scavenging ability. These in vitro results suggest the possibility that glucosamine sulfate could be used effectively as an ingredient in health or functional food, to alleviate oxidative stress.

  9. Inactivation of thrombin by a fucosylated chondroitin sulfate from echinoderm.

    Science.gov (United States)

    Mourão, P A; Boisson-Vidal, C; Tapon-Bretaudière, J; Drouet, B; Bros, A; Fischer, A

    2001-04-15

    A polysaccharide extracted from the sea cucumber body wall has the same backbone structure as the mammalian chondroitin sulfate, but some of the glucuronic acid residues display sulfated fucose branches. These branches confer high anticoagulant activity to the polysaccharide. Since the sea cucumber chondroitin sulfate has analogy in structure with mammalian glycosaminoglycans and sulfated fucans from brown algae, we compared its anticoagulant action with that of heparin and of a homopolymeric sulfated fucan with approximately the same level of sulfation as the sulfated fucose branches found in the sea cucumber polysaccharide. These various compounds differ not only in their anticoagulant potencies but also in the mechanisms of thrombin inhibition. Fucosylated chondroitin sulfate, like heparin, requires antithrombin or heparin cofactor II for thrombin inhibition. Sulfated fucans from brown algae have an antithrombin effect mediated by antithrombin and heparin cofactor II, plus a direct antithrombin effect more pronounced for some fractions. But even in the case of these two polysaccharides, we observed some differences. In contrast with heparin, total inhibition of thrombin in the presence of antithrombin is not achieved with fucosylated chondroitin sulfate, possibly reflecting a less specific interaction. Fucosylated chondroitin sulfate is able to inhibit thrombin generation after stimulation by both contact-activated and thromboplastin-activated systems. It delayed only the contact-induced thrombin generation, as expected for an anticoagulant without direct thrombin inhibition. Overall, the specific spatial array of the sulfated fucose branches in the fucosylated chondroitin sulfate not only confer high anticoagulant activity to the polysaccharide but also determine differences in the way it inhibits thrombin.

  10. Lacrimal gland development and Fgf10-Fgfr2b signaling are controlled by 2-O- and 6-O-sulfated heparan sulfate

    NARCIS (Netherlands)

    Qu, X.; Carbe, C.; Tao, C.; Powers, A.; Lawrence, R.; Kuppevelt, A.H.M.S.M. van; Cardoso, W.V.; Grobe, K.; Esko, J.D.; Zhang, X.

    2011-01-01

    Heparan sulfate, an extensively sulfated glycosaminoglycan abundant on cell surface proteoglycans, regulates intercellular signaling through its binding to various growth factors and receptors. In the lacrimal gland, branching morphogenesis depends on the interaction of heparan sulfate with Fgf10-Fg

  11. Prolactin and Dehydroepiandrosterone Levels in Women with Systemic Lupus Erythematosus: The Role of the Extrapituitary Prolactin Promoter Polymorphism at -1149G/T.

    Science.gov (United States)

    Treadwell, Edward L; Wiley, Kenneth; Word, Beverly; Melchior, William; Tolleson, William H; Gopee, Neera; Hammons, George; Lyn-Cook, Beverly D

    2015-01-01

    Systemic lupus erythematosus (SLE) has shown an association with high levels of prolactin, low levels of dehydroepiandrosterone (DHEA), and induction of inflammatory cytokines in the serum of patients with the disease. This preliminary study examined the relevance of a -1149G/T functional single-nucleotide polymorphism (SNP) (rs1341239) in the promoter of the extrapituitary prolactin gene in a cohort of African American and European American women with lupus. Examination of this SNP revealed that the -1149TT genotype was correlated with higher levels of prolactin in serum and prolactin gene expression (p = 0.0001) in peripheral blood mononuclear cells (PBMCs). Lower levels of DHEA in serum were demonstrated in lupus patients (p = 0.001); those with the -1149TT genotype had the lowest levels of DHEA. Furthermore, a small subset of women who were on DHEA therapy and had a TT genotype showed a significant decrease in prolactin gene expression and lower disease activity scores (SLEDAI). Lupus patients, particularly African Americans, had significantly higher levels of IL-6 (p = 0.0001) and TNF-α (p = 0.042). This study suggests that the -1149TT genotype may be a risk factor for lupus and may predict who could possibly benefit from DHEA therapy; therefore, these results should be validated in a larger cohort with all ethnic groups.

  12. Dehydroepiandrosterone ameliorates H2O2-induced Leydig cells oxidation damage and apoptosis through inhibition of ROS production and activation of PI3K/Akt pathways.

    Science.gov (United States)

    Ding, Xiao; Wang, Dian; Li, Longlong; Ma, Haitian

    2016-01-01

    Dehydroepiandrosterone (DHEA) is widely used as a nutritional supplement, and administration of DHEA produces a number of beneficial effects in the elderly. Many researchers have suggested that DHEA exerts it function after conversion into more biologically active hormones in peripheral target cells. The actions of DHEA in Leydig cells, a major target cell of DHEA biotransformation in males, are not clear. The present study found that DHEA increased cell viability and decreased reactive oxygen species (ROS) and malondialdehyde contents in H2O2-induced Leydig cells. DHEA significantly increased the activities of superoxide dismutase, catalase and peroxidase, and decreased the DNA damage in H2O2-induced Leydig cells. Apoptosis was significant decreased in H2O2-induced Leydig cells after DHEA treatment. DHEA inhibited the loss of mitochondrial membrane potential (ΔΨm) and the upregulation of the caspase-3 protein level induced by H2O2 in Leydig cells. DHEA also reversed the decrease in PI3K and p-Akt protein levels induced by H2O2. These data showed that DHEA could ameliorate H2O2-induced oxidative damage by increasing anti-oxidative enzyme activities, which resulted in reduced ROS content, and decreased apoptosis, mainly by preventing the loss of ΔΨm and inhibiting caspase-3 protein levels via activation of PI3K/Akt signaling pathways. These results increase our understanding of the molecular mechanism of the anti-ageing effect of DHEA.

  13. The effects of dehydroepiandrosterone (DHEA) in the treatment of depression and depressive symptoms in other psychiatric and medical illnesses: a systematic review.

    Science.gov (United States)

    Peixoto, Clayton; Devicari Cheda, Julio Nelson; Nardi, Antonio Egidio; Veras, Andre Barciela; Cardoso, Adriana

    2014-01-01

    International interest on the benefits of using the steroid hormone Dehydroepiandrosterone (DHEA) on various aspects of human health, including the regulation of mood, is increasing. This study aimed to review the scientific literature on the use of DHEA in the treatment of depression and depressive symptoms in other psychiatric and medical illnesses. PubMed, ISI Web of Knowledge and Virtual Health Library (VHL) databases were independently searched by two researchers using the following terms: depression, treatment, DHEA, and mood. Clinical studies were considered eligible when subjects were treated with DHEA and psychological assessments of depression were conducted. No time limits or language for this research were imposed. One 183 references were identified, and 22 references were selected to compose this review. Significant improvements related to the use of DHEA in patients with depression were observed, in addition to improvements in depressive symptoms in patients with schizophrenia, anorexia nervosa, HIV and adrenal insufficiency. No significant improvements were observed regarding depressive symptoms in patients with fibromyalgia; the results observed in patients with autoimmune diseases and healthy individuals remain contradictory. Although the selected studies demonstrated good methodological applications, most studies consisted of small samples, and only 3 studies were conducted in a young population. Therefore, we concluded that the studies published to date indicate promising results regarding the use of DHEA in the treatment of depression and depressive symptoms, especially in depression that is mild or resistant to conventional therapy.

  14. Efficacy of intravaginal dehydroepiandrosterone (DHEA) on moderate to severe dyspareunia and vaginal dryness, symptoms of vulvovaginal atrophy, and of the genitourinary syndrome of menopause.

    Science.gov (United States)

    Labrie, Fernand; Archer, David F; Koltun, William; Vachon, Andrée; Young, Douglas; Frenette, Louise; Portman, David; Montesino, Marlene; Côté, Isabelle; Parent, Julie; Lavoie, Lyne; Beauregard, Adam; Martel, Céline; Vaillancourt, Mario; Balser, John; Moyneur, Érick

    2016-03-01

    The aim of this study is to confirm the local beneficial effects of intravaginal dehydroepiandrosterone (DHEA, Prasterone) on moderate to severe dyspareunia or pain at sexual activity, the most frequent symptom of vulvovaginal atrophy due to menopause or genitourinary syndrome of menopause (GSM). In a prospective, randomized, double-blind, and placebo-controlled phase III clinical trial, the effect of daily intravaginal 0.50% DHEA (6.5 mg) (Prasterone, EndoCeutics) was examined on four coprimary objectives, namely percentage of parabasal cells, percentage or superficial cells, vaginal pH, and moderate to severe pain at sexual activity (dyspareunia) identified by the women as their most bothersome vulvovaginal atrophy symptom. The intent-to-treat population included 157 and 325 women in the placebo and DHEA-treated groups, respectively. After daily intravaginal administration of 0.50% DHEA for 12 weeks, when compared to baseline by the analysis of covariance test, the percentage of parabasal cells decreased by 27.7% over placebo (P DHEA (Prasterone) has shown clinically and highly statistically significant effects on the four coprimary parameters suggested by the US Food and Drug Administration. The strictly local action of Prasterone is in line with the absence of significant drug-related adverse events, thus showing the high benefit-to-risk ratio of this treatment based upon the novel understanding of the physiology of sex steroids in women.

  15. Administration of dehydroepiandrosterone (DHEA) increases serum levels of androgens and estrogens but does not enhance short-term memory in post-menopausal women.

    Science.gov (United States)

    Merritt, Paul; Stangl, Bethany; Hirshman, Elliot; Verbalis, Joseph

    2012-11-05

    The current study examines the effect of administering dehydroepiandrosterone (DHEA) on short-term memory. This experiment used a double-blind placebo-controlled cross-over design to explore the effects of a four week regimen of 50 mg oral DHEA on performance on the digit span, verbal span, and modified Sternberg (Oberauer) tasks. The results demonstrate that the current regimen of drug administration significantly increases serum levels of DHEA, DHEAS, testosterone and estrone and substantially alters the patterns of correlations among the serum levels of these hormones. Despite this substantial change in the hormonal milieu, DHEA administration produced no beneficial effects on cognitive performance in the digit span, verbal span, or modified Sternberg paradigm tasks. Ancillary analyses of the relation between hormone levels and cognitive performance demonstrated a strong positive correlation between DHEA levels and performance on digit span forward/backward and verbal span forward in the placebo drug condition, but not in the DHEA condition. We interpret the juxtaposition of the null results of DHEA administration and the correlation of DHEA levels and performance in the placebo condition to indicate that the referenced correlations arise because a third variable (i.e., age) is associated with both performance and DHEA levels. Additional analyses supported this hypothesis. Copyright © 2012 Elsevier B.V. All rights reserved.

  16. Analysis of clinical symptomatology, extrapyramidal symptoms and neurocognitive dysfunction following dehydroepiandrosterone (DHEA) administration in olanzapine treated schizophrenia patients: a randomized, double-blind placebo controlled trial.

    Science.gov (United States)

    Strous, Rael D; Stryjer, Rafael; Maayan, Rachel; Gal, Gilad; Viglin, Dina; Katz, Elena; Eisner, Dana; Weizman, Abraham

    2007-02-01

    Several studies have demonstrated the effective use of dehydroepiandrosterone (DHEA) in the management of mood, however studies of its use in psychosis remain limited. The aim of this study was to investigate for the first time efficacy of DHEA augmentation with standardized antipsychotic medication (olanzapine) and to explore effects of DHEA augmentation on side-effect profiles including weight gain, glucose tolerance, aggression, quality of life and neurocognitive function. Finally, we aimed to analyze any relationship between plasma levels and clinical response to DHEA administration. Forty patients with chronic schizophrenia stabilized on olanzapine were randomized in double-blind fashion to receive either DHEA (titrated up to 150mg) or placebo augmentation for a period of 12-weeks. Blood samples were collected at baseline, mid-study and study completion. Results indicated improvement of negative symptoms (SANS scale) even when baseline scores were controlled as a covariate. Some improvement in Parkinsonism and akathisia compared to baseline was seen in patients receiving DHEA. No change in psychosis as reflected by the PANSS was noted. Patients receiving DHEA appeared to demonstrate relatively stable glucose levels compared to controls at the end of the study. An improvement in cognitive performance (most notably memory), which did not reach significance due to low sample number, was observed following DHEA administration. Results further suggest preliminary evidence of involvement of the neurosteroid system in schizophrenia pathophysiology, and confirm initial "cautious" findings identifying an agent capable of improving negative symptoms and certain features of extrapyramidal side effects.

  17. Prolactin and Dehydroepiandrosterone Levels in Women with Systemic Lupus Erythematosus: The Role of the Extrapituitary Prolactin Promoter Polymorphism at −1149G/T

    Directory of Open Access Journals (Sweden)

    Edward L. Treadwell

    2015-01-01

    Full Text Available Systemic lupus erythematosus (SLE has shown an association with high levels of prolactin, low levels of dehydroepiandrosterone (DHEA, and induction of inflammatory cytokines in the serum of patients with the disease. This preliminary study examined the relevance of a −1149G/T functional single-nucleotide polymorphism (SNP (rs1341239 in the promoter of the extrapituitary prolactin gene in a cohort of African American and European American women with lupus. Examination of this SNP revealed that the −1149TT genotype was correlated with higher levels of prolactin in serum and prolactin gene expression (p=0.0001 in peripheral blood mononuclear cells (PBMCs. Lower levels of DHEA in serum were demonstrated in lupus patients (p=0.001; those with the −1149TT genotype had the lowest levels of DHEA. Furthermore, a small subset of women who were on DHEA therapy and had a TT genotype showed a significant decrease in prolactin gene expression and lower disease activity scores (SLEDAI. Lupus patients, particularly African Americans, had significantly higher levels of IL-6 (p=0.0001 and TNF-α (p=0.042. This study suggests that the −1149TT genotype may be a risk factor for lupus and may predict who could possibly benefit from DHEA therapy; therefore, these results should be validated in a larger cohort with all ethnic groups.

  18. Effects of Angiotensin-Converting Enzyme Inhibitor Derived from Tropaeolum majus L. in Rat Preimplantation Embryos: Evidence for the Dehydroepiandrosterone and Estradiol Role

    Directory of Open Access Journals (Sweden)

    Emerson Luiz Botelho Lourenço

    2014-01-01

    Full Text Available Although several studies have shown the inhibitory effects of Tropaeolum majus extracts (HETM on angiotensin-converting enzyme (ACE activity, no studies have been carried out during the beginning of pregnancy, when humoral and hormonal imbalance may affect zygote and early embryo transport. This study investigates whether HETM can affect embryonic development when administered during the one-cell-blastocyst period. Pregnant Wistar rats received orally the HETM (3, 30, and 300 mg/kg/day from the 1st to the 7th gestational day. Rats were killed on the 8th day of pregnancy and the following parameters were evaluated: clinical symptoms of toxicity (including organ weights, number of corpora lutea, implants per group, preimplantation losses ratio, and the serum levels of dehydroepiandrosterone (DHEA, estradiol, and progesterone. No clinical symptoms of maternal toxicity were evidenced. On the 8th day of pregnancy, the levels of DHEA and estradiol were increased and significant preimplantation losses were observed at all doses used. The present study reveals that the HETM can raise levels of DHEA and estradiol and induce difficulty in the embryo implantation in the early stages of pregnancy. The data contributes significantly to the safety aspects of using this natural product when trying to get pregnant or during pregnancy.

  19. High Levels of 17β-Estradiol Are Associated with Increased Matrix Metalloproteinase-2 and Metalloproteinase-9 Activity in Tears of Postmenopausal Women with Dry Eye

    Directory of Open Access Journals (Sweden)

    Guanglin Shen

    2016-01-01

    Full Text Available Purpose. To determine the serum levels of sex steroids and tear matrix metalloproteinases (MMP 2 and 9 concentrations in postmenopausal women with dry eye. Methods. Forty-four postmenopausal women with dry eye and 22 asymptomatic controls were enrolled. Blood was drawn and analyzed for serum levels of sex steroids and lipids. Then, the following tests were performed: tear collection, Ocular Surface Disease Index (OSDI questionnaire, fluorescein tear film break-up time (TBUT, corneal fluorescein staining, Schirmer test, and conjunctival impression cytology. The conjunctival mRNA expression and tear concentrations of MMP-2 and MMP-9 were measured. Results. Serum 17β-estradiol levels were significantly higher in the dry eye subjects than in the controls (P=0.03, whereas there were no significant differences in levels of testosterone, dehydroepiandrosterone sulfate (DHEA-S, and progesterone. Tear MMP-2 and MMP-9 concentrations (P<0.001, as well as the MMP-9 mRNA expression in conjunctival samples (P=0.02, were significantly higher in dry eye subjects than in controls. Serum 17β-estradiol levels were positively correlated with tear MMP-2 and MMP-9 concentrations and negatively correlated with Schirmer test values. Conclusions. High levels of 17β-estradiol are associated with increased matrix metalloproteinase-2 and metalloproteinase-9 activity in tears of postmenopausal women with dry eye.

  20. Comparison between effects of myo-inositol and D-chiro-inositol on ovarian function and metabolic factors in women with PCOS.

    Science.gov (United States)

    Pizzo, Alfonsa; Laganà, Antonio Simone; Barbaro, Luisa

    2014-03-01

    Myo-inositol and D-chiro-inositol are capable of improving the ovarian function and metabolism of polycystic ovary syndrome (PCOS) patients. The aim of this work is to compare the effects of myo-inositol and D-chiro-inositol in PCOS. We enrolled 50 patients, with homogeneous bio-physical features, affected by PCOS and menstrual irregularities, and we randomly divided them into two groups: 25 were treated with 4 g of myo-inositol/die plus 400 mcg of folic acid/die orally for six months, 25 with 1 g of D-chiro-inositol/die plus 400 mcg of folic acid/die orally for six months. We analyzed in both groups pre-treatment and post-treatment BMI, systolic and diastolic blood pressure, Ferriman-Gallwey score, Cremoncini score, serum LH, LH/FSH ratio, total and free testosterone, dehydroepiandrosterone sulfate (DHEA-S), Δ-4-androstenedione, SHBG, prolactin, glucose/immunoreactive insulin (IRI) ratio, homeostatic model assessment (HOMA) index, and the resumption of regular menstrual cycles. Both the isoforms of inositol were effective in improving ovarian function and metabolism in patients with PCOS, although myo-inositol showed the most marked effect on the metabolic profile, whereas D-chiro-inositol reduced hyperandrogenism better.

  1. Comparison of sex hormonal and metabolic profiles between omnivores and vegetarians in pre- and post-menopausal women.

    Science.gov (United States)

    Karelis, Antony D; Fex, Annie; Filion, Marie-Eve; Adlercreutz, Herman; Aubertin-Leheudre, Mylène

    2010-07-01

    The purpose of the present study was to investigate the sex hormonal and metabolic profiles in vegetarians and compare these with the profiles in omnivores. The design of the present study was cross-sectional. The study sample of pre- and post-menopausal women included forty-one omnivores and twenty-one vegetarians. Thereafter we determined: (1) plasma sex hormones, (2) fasting insulin, NEFA as well as apo-A and apo-B, (3) BMI, (4) a dietary profile (3 d dietary records), (5) physical activity and (6) total faecal excretion per 72 h and total urinary excretion per 72 h. Vegetarians showed higher levels of sex hormone-binding globulin (SHBG), apo-A, total faecal excretion per 72 h and total fibre intake as well as lower levels of apo-B, free oestradiol, free testosterone, dehydroepiandrosterone sulfate (DHEA-s) and BMI. Interestingly, after controlling for BMI, significant differences between groups still persisted except for apo-B. Moreover, stepwise regression analysis showed that total fibre intake explained 15.2 % of the variation in SHBG in our cohort, which accounted for the greatest source of unique variance. Results of the present study indicate that pre- and post-menopausal vegetarians present higher concentrations of SHBG, which could be explained, in part, by higher levels of fibre intake. This may explain, at least in part, the lower risk of developing type 2 diabetes.

  2. Utilization of sulfate additives in biomass combustion: fundamental and modeling aspects

    DEFF Research Database (Denmark)

    Wu, Hao; Jespersen, Jacob Boll; Grell, Morten Nedergaard;

    2013-01-01

    Sulfates, such as ammonium sulfate, aluminum sulfate and ferric sulfate, are effective additives for converting the alkali chlorides released from biomass combustion to the less harmful alkali sulfates. Optimization of the use of these additives requires knowledge on their decomposition rate...... and product distribution under high temperature conditions. In the present work, the decomposition of ammonium sulfate, aluminum sulfate and ferric sulfate was studied respectively in a fast-heating rate thermogravimetric analyzer for deriving a kinetic model to describe the process. The yields of SO2 and SO3...... of different sulfates indicated that ammonium sulfate has clearly strongest sulfation power towards KCl at temperatures below 800oC, whereas the sulfation power of ferric and aluminum sulfates exceeds clearly that of ammonium sulfate between 900 and 1000oC. However, feeding gaseous SO3 was found to be most...

  3. Effects of sulfate deprivation on the production of chondroitin/dermatan sulfate by cultures of skin fibroblasts from normal and diabetic individuals

    Energy Technology Data Exchange (ETDEWEB)

    Silbert, C.K.; Humphries, D.E.; Palmer, M.E.; Silbert, J.E. (Veterans Administration Outpatient Clinic, Boston, MA (USA))

    1991-02-15

    Human skin fibroblast monolayer cultures from two normal men, three Type I diabetic men, and one Type I diabetic woman were incubated with (3H)glucosamine in the presence of diminished concentrations of sulfate. Although total synthesis of (3H)chondroitin/dermatan glycosaminoglycans varied somewhat between cell lines, glycosaminoglycan production was not affected within any line when sulfate levels were decreased from 0.3 mM to 0.06 mM to 0.01 mM to 0 added sulfate. Lowering of sulfate concentrations resulted in diminished sulfation of chondroitin/dermatan in a progressive manner, so that overall sulfation dropped to as low as 19% for one of the lines. Sulfation of chondroitin to form chondroitin 4-sulfate and chondroitin 6-sulfate was progressively and equally affected by decreasing the sulfate concentration in the culture medium. However, sulfation to form dermatan sulfate was preserved to a greater degree, so that the relative proportion of dermatan sulfate to chondroitin sulfate increased. Essentially all the nonsulfated residues were susceptible to chondroitin AC lyase, indicating that little epimerization of glucuronic acid residues to iduronic acid had occurred in the absence of sulfation. These results confirm the previously described dependency of glucuronic/iduronic epimerization on sulfation, and indicate that sulfation of the iduronic acid-containing disaccharide residues of dermatan can take place with sulfate concentrations lower than those needed for 6-sulfation and 4-sulfation of the glucuronic acid-containing disaccharide residues of chondroitin. There were considerable differences among the six fibroblast lines in susceptibility to low sulfate medium and in the proportion of chondroitin 6-sulfate, chondroitin 4-sulfate, and dermatan sulfate. However, there was no pattern of differences between normals and diabetics.

  4. Sulfated fucan as support for antibiotic immobilization.

    Science.gov (United States)

    Araújo, P M; Oliveira, G B; Córdula, C R; Leite, E L; Carvalho Jr, L B; Silva, M P C

    2004-03-01

    Xylofucoglucuronan from Spatoglossum schröederi algae was tested as a support for antibiotic immobilization. The polysaccharide (20 mg in 6 ml) was first activated using carbodiimide, 1-ethyl-3-(3-dimethylamino-propyl)carbodiimide methiodide (20 mg in 2 ml), under stirring for 1 h at 25 masculine C and pH from 4.5 to 5.0. After adjusting the pH to 8.0, either gentamicin or amikacin (62.5 mg in 1.25 ml) was then immobilized on this chemically modified polysaccharide with shaking for 24 h in a cold room. Infrared spectra of the activated carbodiimide xylofucoglucuronan showed two bands to carbonyl (C=O at 1647.9 and 1700.7 cm(-1)) and to amide (C-NH2) groups (1662.8 and 1714.0 cm(-1)). Microbial characterization of the derivatives was carried out by the disk diffusion method using Staphylococcus aureus or Klebsiella pneumoniae incorporated in Müller Hinton medium. Inhibition halos of bacterial growth were observed for the antibiotics immobilized on this sulfated heteropolysaccharide before and after dialysis. However, the halos resulting from the samples after dialysis were much smaller, suggesting that dialysis removed either non-covalently bound antibiotic or other small molecules. In contrast, bacterial growth was not inhibited by either xylofucoglucuronan or its activated form or by gentamicin or amikacin after dialysis. An additional experiment was carried out which demonstrated that the sulfated heteropolysaccharide was hydrolyzed by the microorganism. Therefore, the antibiotic immobilized on xylofucoglucuronan can be proposed as a controlled drug delivery system. Furthermore, this sulfated heteropolysaccharide can be extracted easily from sea algae Spatoglossum schröederi.

  5. Sulfated fucan as support for antibiotic immobilization

    Directory of Open Access Journals (Sweden)

    Araújo P.M.

    2004-01-01

    Full Text Available Xylofucoglucuronan from Spatoglossum schröederi algae was tested as a support for antibiotic immobilization. The polysaccharide (20 mg in 6 ml was first activated using carbodiimide, 1-ethyl-3-(3-dimethylamino-propylcarbodiimide methiodide (20 mg in 2 ml, under stirring for 1 h at 25ºC and pH from 4.5 to 5.0. After adjusting the pH to 8.0, either gentamicin or amikacin (62.5 mg in 1.25 ml was then immobilized on this chemically modified polysaccharide with shaking for 24 h in a cold room. Infrared spectra of the activated carbodiimide xylofucoglucuronan showed two bands to carbonyl (C = O at 1647.9 and 1700.7 cm-1 and to amide (CÝ-NH2 groups (1662.8 and 1714.0 cm-1. Microbial characterization of the derivatives was carried out by the disk diffusion method using Staphylococcus aureus or Klebsiella pneumoniae incorporated in Müller Hinton medium. Inhibition halos of bacterial growth were observed for the antibiotics immobilized on this sulfated heteropolysaccharide before and after dialysis. However, the halos resulting from the samples after dialysis were much smaller, suggesting that dialysis removed either non-covalently bound antibiotic or other small molecules. In contrast, bacterial growth was not inhibited by either xylofucoglucuronan or its activated form or by gentamicin or amikacin after dialysis. An additional experiment was carried out which demonstrated that the sulfated heteropolysaccharide was hydrolyzed by the microorganism. Therefore, the antibiotic immobilized on xylofucoglucuronan can be proposed as a controlled drug delivery system. Furthermore, this sulfated heteropolysaccharide can be extracted easily from sea algae Spatoglossum schröederi.

  6. Synthesis and characterization of novel cellulose ether sulfates.

    Science.gov (United States)

    Rohowsky, Juta; Heise, Katja; Fischer, Steffen; Hettrich, Kay

    2016-05-20

    The synthesis and characterization of novel cellulose sulfate derivatives was reported. Various cellulose ethers were prepared in a homogeneous reaction with common sulfating agents. The received product possess different properties in dependence on the reaction conditions like sulfating agent, solvent, reaction time and reaction temperature. The cellulose ether sulfates are all soluble in water, they rheological behavior could be determined by viscosity measurements and the determination of the sulfur content by elemental analysis lead to a resulting degree of substitution ascribed to sulfate groups (DSSul) of the product. A wide range of products from DSSul 0.1 to DSSul 2.7 will be obtained. Furthermore the cellulose sulfate ethers could be characterized by Raman spectroscopy.

  7. Chemical leukoderma induced by dimethyl sulfate*

    Science.gov (United States)

    Gozali, Maya Valeska; Zhang, Jia-an; Yi, Fei; Zhou, Bing-rong; Luo, Dan

    2016-01-01

    Chemical leukoderma occurs due to the toxic effect of a variety of chemical agents. Mechanisms include either destruction or inhibition of melanocytes. We report two male patients (36 and 51 years old) who presented with multiple hypopigmented macules and patches on the neck, wrist, and legs after exposure to dimethyl sulfate in a chemical industry. Physical examination revealed irregular depigmentation macules with sharp edges and clear hyperpigmentation around the lesions. History of repeated exposure to a chemical agent can help the clinical diagnosis of chemical leukoderma. This diagnosis is very important for prognosis and therapeutic management of the disease.

  8. New Bioactive Alkyl Sulfates from Mediterranean Tunicates

    Directory of Open Access Journals (Sweden)

    Marialuisa Menna

    2012-10-01

    Full Text Available Chemical investigation of two species of marine ascidians, Aplidium elegans and Ciona edwardsii, collected in Mediterranean area, led to isolation of a series of alkyl sulfates (compounds 1–5 including three new molecules 1–3. Structures of the new metabolites have been elucidated by spectroscopic analysis. Based on previously reported cytotoxic activity of these type of molecules, compounds 1–3 have been tested for their effects on the growth of two cell lines, J774A.1 (BALB/c murine macrophages and C6 (rat glioma in vitro. Compounds 1 and 2 induced selective concentration-dependent mortality on J774A.1 cells.

  9. Sulfation patterns determine cellular internalization of heparin-like polysaccharides

    OpenAIRE

    Raman, Karthik; Mencio, Caitlin; Desai, Umesh R.; Kuberan, Balagurunathan

    2013-01-01

    Heparin is a highly sulfated polysaccharide which serves biologically relevant roles as an anticoagulant and anti-cancer agent. While it is well known that modification of heparin’s sulfation pattern can drastically influence its ability to bind growth factors and other extracellular molecules, very little is known about the cellular uptake of heparin and the role sulfation patterns serve in affecting its internalization. In this study, we chemically synthesized several fluorescently-labeled ...

  10. Glycosaminoglycan modifications in Duchenne muscular dystrophy: specific remodeling of chondroitin sulfate/dermatan sulfate.

    Science.gov (United States)

    Negroni, Elisa; Henault, Emilie; Chevalier, Fabien; Gilbert-Sirieix, Marie; Van Kuppevelt, Toin H; Papy-Garcia, Dulce; Uzan, Georges; Albanese, Patricia

    2014-08-01

    Widespread skeletal muscle degeneration and impaired regeneration lead to progressive muscle weakness and premature death in patients with Duchenne muscular dystrophy (DMD). Dystrophic muscles are progressively replaced by nonfunctional tissue because of exhaustion of muscle precursor cells and excessive accumulation of extracellular matrix (ECM). Sulfated glycosaminoglycans (GAGs) are components of the ECM and are increasingly implicated in the regulation of biologic processes, but their possible role in the progression of DMD pathology is not understood. In the present study, we performed immunohistochemical and biochemical analyses of endogenous GAGs in skeletal muscle biopsies of 10 DMD patients and 11 healthy individuals (controls). Immunostaining targeted to specific GAG species showed greater deposition of chondroitin sulfate (CS)/dermatan (DS) sulfate in DMD patient biopsies versus control biopsies. The selective accumulation of CS/DS in DMD biopsies was confirmed by biochemical quantification assay. In addition, high-performance liquid chromatography analysis demonstrated a modification of the sulfation pattern of CS/DS disaccharide units in DMD muscles. In conclusion, our data open up a new path of investigation and suggest that GAGs could represent a new and original therapeutic target for improving the success of gene or cell therapy for the treatment of muscular dystrophies.

  11. Sulfation of heparan sulfate associated with amyloid-beta plaques in patients with Alzheimer's disease.

    NARCIS (Netherlands)

    Bruinsma, I.B.; Riet, L. te; Gevers, T.; Dam, G.B. ten; Kuppevelt, A.H.M.S.M. van; David, G.; Kusters, B.; Waal, R.M.W. de; Verbeek, M.M.

    2010-01-01

    Alzheimer's disease (AD) is characterized by pathological lesions such as amyloid-beta (Abeta) plaques and cerebral amyloid angiopathy. Both these lesions consist mainly of aggregated Abeta protein and this aggregation is affected by macromolecules such as heparan sulfate (HS) proteoglycans.

  12. Inter vs. intraglycosidic acetal linkages control sulfation pattern in semi-synthetic chondroitin sulfate.

    Science.gov (United States)

    Laezza, Antonio; De Castro, Cristina; Parrilli, Michelangelo; Bedini, Emiliano

    2014-11-04

    Microbial-sourced unsulfated chondroitin could be converted into chondroitin sulfate (CS) polysaccharide by a multi-step strategy relying upon benzylidenation and acetylation reactions as key-steps for its regioselective protection. By conducting the two reactions one- or two-pots, CSs with different sulfation patterns could be obtained at the end of the semi-synthesis. In particular, a CS polysaccharide possessing sulfate groups randomly distributed between positions 4 and 6 of N-acetyl-galactosamine (GalNAc) units could be obtained through the two-pots route, whereas the one-pot pathway allowed an additional sulfation at position 3 of some glucuronic acid (GlcA) units. This difference was ascribed to the stabilization of a labile interglycosidic benzylidene acetal involving positions O-3 and O-6 of some GlcA and GalNAc, respectively, when the benzylidene-acetylation reactions were conducted in a one-pot fashion. Isolation and characterization of a polysaccharide intermediate showing interglycosidic acetal moieties was accomplished.

  13. REFINEMENT OF THE CRYSTAL STRUCTURE OF GUANIDINIUM ALUMINUM SULFATE HEXAHYDRATE.

    Science.gov (United States)

    FERROELECTRIC CRYSTALS, * CRYSTAL STRUCTURE ), (*GUANIDINES, CRYSTAL STRUCTURE ), (*ALUMINUM COMPOUNDS, CRYSTAL STRUCTURE ), SULFATES, HYDRATES, X RAY DIFFRACTION, CHROMIUM COMPOUNDS, CRYSTAL LATTICES, CHEMICAL BONDS

  14. Cloud water chemistry and the production of sulfates in clouds

    Science.gov (United States)

    Hegg, D. A.; Hobbs, P. V.

    1981-01-01

    Measurements are presented of the pH and ionic content of water collected in clouds over western Washington and the Los Angeles Basin. Evidence for sulfate production in some of the clouds is presented. Not all of the sulfur in the cloud water was in the form of sulfate. However, the measurements indicate that the production of sulfate in clouds is of considerable significance in the atmosphere. Comparison of field measurements with model results show reasonable agreement and suggest that the production of sulfate in cloud water is a consequence of more than one conversion mechanism.

  15. Theoretical study on the reactivity of sulfate species with hydrocarbons

    Science.gov (United States)

    Ma, Q.; Ellis, G.S.; Amrani, A.; Zhang, T.; Tang, Y.

    2008-01-01

    The abiotic, thermochemically controlled reduction of sulfate to hydrogen sulfide coupled with the oxidation of hydrocarbons, is termed thermochemical sulfate reduction (TSR), and is an important alteration process that affects petroleum accumulations in nature. Although TSR is commonly observed in high-temperature carbonate reservoirs, it has proven difficult to simulate in the laboratory under conditions resembling nature. The present study was designed to evaluate the relative reactivities of various sulfate species in order to provide greater insight into the mechanism of TSR and potentially to fill the gap between laboratory experimental data and geological observations. Accordingly, quantum mechanics density functional theory (DFT) was used to determine the activation energy required to reach a potential transition state for various aqueous systems involving simple hydrocarbons and different sulfate species. The entire reaction process that results in the reduction of sulfate to sulfide is far too complex to be modeled entirely; therefore, we examined what is believed to be the rate limiting step, namely, the reduction of sulfate S(VI) to sulfite S(IV). The results of the study show that water-solvated sulfate anions SO42 - are very stable due to their symmetrical molecular structure and spherical electronic distributions. Consequently, in the absence of catalysis, the reactivity of SO42 - is expected to be extremely low. However, both the protonation of sulfate to form bisulfate anions (HSO4-) and the formation of metal-sulfate contact ion-pairs could effectively destabilize the sulfate molecular structure, thereby making it more reactive. Previous reports of experimental simulations of TSR generally have involved the use of acidic solutions that contain elevated concentrations of HSO4- relative to SO42 -. However, in formation waters typically encountered in petroleum reservoirs, the concentration of HSO4- is likely to be significantly lower than the levels

  16. An Instrument to Measure Aircraft Sulfate Particle Emissions Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Aerodyne is developing a sulfate detection instrument, based on the Tunable Infrared Laser Differential Absorption Spectrophotometer (TILDAS) technology and...

  17. Sulfate Reduction in Groundwater: Characterization and Applications for Remediation

    Energy Technology Data Exchange (ETDEWEB)

    Miao, Z.; Brusseau, M. L.; Carroll, Kenneth C.; Carreon-Diazconti, C.; Johnson, B.

    2012-06-01

    Sulfate is ubiquitous in groundwater, with both natural and anthropogenic sources. Sulfate reduction reactions play a significant role in mediating redox conditions and biogeochemical processes for subsurface systems. They also serve as the basis for innovative in-situ methods for groundwater remediation. An overview of sulfate reduction in subsurface environments is provided, with a specific focus on implications for groundwater remediation. A case study presenting the results of a pilot-scale ethanol injection test illustrates the advantages and difficulties associated with the use of electron-donor amendments for sulfate remediation.

  18. Basement membrane chondroitin sulfate proteoglycans: localization in adult rat tissues

    DEFF Research Database (Denmark)

    McCarthy, K J; Couchman, J R

    1990-01-01

    Heparan sulfate proteoglycans have been described as the major proteoglycan component of basement membranes. However, previous investigators have also provided evidence for the presence of chondroitin sulfate glycosaminoglycan in these structures. Recently we described the production...... and characterization of core protein-specific monoclonal antibodies (MAb) against a chondroitin sulfate proteoglycan (CSPG) present in Reichert's membrane, a transient extra-embryonic structure of rodents. This CSPG was also demonstrated to be present in adult rat kidney. We report here the tissue distribution...... sulfate proteoglycans previously described....

  19. The "in and out" of glucosamine 6-O-sulfation: the 6th sense of heparan sulfate.

    Science.gov (United States)

    El Masri, Rana; Seffouh, Amal; Lortat-Jacob, Hugues; Vivès, Romain R

    2016-11-03

    The biological properties of Heparan sulfate (HS) polysaccharides essentially rely on their ability to bind and modulate a multitude of protein ligands. These interactions involve internal oligosaccharide sequences defined by their sulfation patterns. Amongst these, the 6-O-sulfation of HS contributes significantly to the polysaccharide structural diversity and is critically involved in the binding of many proteins. HS 6-O-sulfation is catalyzed by 6-O-sulfotransferases (6OSTs) during biosynthesis, and it is further modified by the post-synthetic action of 6-O-endosulfatases (Sulfs), two enzyme families that remain poorly characterized. The aim of the present review is to summarize the contribution of 6-O-sulfates in HS structure/function relationships and to discuss the present knowledge on the complex mechanisms regulating HS 6-O-sulfation.

  20. Controls of Soluble Al in Experimental Acid Sulfate Conditions and Acid Sulfate Soils

    Institute of Scientific and Technical Information of China (English)

    LINCHUXIA; M.D.MELVILLE

    1997-01-01

    The controls of soluble Al concentration were examined in three situations of acid sulfate conditions:1) experimental acid sulfate conditions by addition of varying amounts of Al(OH)3(gibbsite) into a sequence of H2SO4 solutions;2)experimental acid sulfate conditions by addition of the same sequence of H2SO4 solutions into two non-cid sulfacte soil samples with known amounts of acid oxalate extractable Al; and 3) actual acid sulfate soil conditions.The experiment using gibbsite as an Al-bearing mineral showed that increase in the concentration of H2SO4 solution increased the soluble Al concentration,accompanied by a decrease i the solution pH, Increasing amount of gibbsite added to the H2SO4 solutions also increased soluble Al concentration,but resulted in an increase in solution pH.Within the H2SO4 concentration range of 0.0005-0.5mol L-1 and the Al(OH)3 range of 0.01-0.5g(in 25 mL of H2SO4 solutions),the input of H2SO4 had the major control on soluble Al Concentration and pH .The availability of Al(OH)3,however,was responsible for the spread fo the various sample points,with a tendency that the samples containing more gibbsite had a higher soluble Al concentration than those containing less gibbsite at equivalent pH levels.The experimental results from treatment of soil samples with H2SO4 solutions and the analytical results of acid sulfate soils also showed the similar trend.

  1. Papillomavirus microbicidal activities of high-molecular-weight cellulose sulfate, dextran sulfate, and polystyrene sulfonate.

    Science.gov (United States)

    Christensen, N D; Reed, C A; Culp, T D; Hermonat, P L; Howett, M K; Anderson, R A; Zaneveld, L J

    2001-12-01

    The high-molecular-weight sulfated or sulfonated polysaccharides or polymers cellulose sulfate, dextran sulfate, and polystyrene sulfonate were tested for microbicidal activity against bovine papillomavirus type 1 (BPV-1) and human papillomavirus type 11 (HPV-11) and type 40 (HPV-40). In vitro assays included the BPV-1-induced focus-forming assay and transient infection of human A431 cells with HPVs. The compounds were tested for microbicidal activity directly by preincubation with virus prior to addition to cell cultures and indirectly by addition of virus to compound-treated cells and to virus-coated cells to test inactivation of the virus after virus-cell binding. The data indicated that all three compounds showed direct microbicidal activity with 50% effective concentrations between 10 to 100 microg/ml. These concentrations were nontoxic to cell cultures for both assays. When a clone of C127 cells was tested for microbicidal activity, approximately 10-fold-less compound was required to achieve a 50% reduction in BPV-1-induced foci than for the uncloned parental C127 cells. Pretreatment of cells with compound prior to addition of virus also demonstrated strong microbicidal activity with dextran sulfate and polystyrene sulfonate, but cellulose sulfate required several orders of magnitude more compound for virus inactivation. Polystyrene sulfonate prevented subsequent infection of HPV-11 after virus-cell binding, and this inactivation was observed up to 4 h after addition of virus. These data indicate that the polysulfated and polysulfonated compounds may be useful nontoxic microbicidal compounds that are active against a variety of sexually transmitted disease agents including papillomaviruses.

  2. Synergistic Extraction of Gallium for Sulfate Solution

    Institute of Scientific and Technical Information of China (English)

    DENGTong; HUANGLijuan; 等

    2002-01-01

    A novel extractant mixture, di-2-ethylhexyl phosphate (DEHPA) plus HX, was propose and tested for recovering gallium from sulfate solution.It was found that the extraction capacity of DEPHA for gallium from sulfate solution could be enhanced significantly due to the synergistic effect of acidix extractant HX. Gallium extraction is negligible below pH 0 and highly sensitive to pH of aqueous phase in the range from 0 to 1, and satisfactory extraction can be gained at pH>1. More than 96% Ga extraction was obtained using 15% DEHPA plus 2% HX. Although Fe(Ⅲ) was found to be extracted preferentially to Ga (Ⅲ), effective extraction of Ga (Ⅲ) was possible by reducing ferric to the ferrous state prior to extraction. A loaded organic phase containing 0.48g·L-1 Ga could be produced from solution of 0.12g·L-1 Ga at A/O ratio of 4:1 via three mixer-settler operation stages. Gallium was stripped quantitatively from the loaded organic phase with 1.5mol·L-1 of sulfuric acid.

  3. Molecular Structure of Aminoguanidine Sulfate Monohydrate

    Institute of Scientific and Technical Information of China (English)

    CHEN Hong-yan; ZHANG Tong-lai; QIAO Xiao-jing; YANG Li; SHAO Feng-lei

    2006-01-01

    The single crystal of aminoguanidine sulfate monohydrate [(AG)2SO4·H2O] is obtained and its structure is determined by X-ray diffraction analysis. The compound crystallizes in orthorhombic system with space group Pnma and the empirical formula C2H16N8O5S. The unit cell parameters are as follows: a=0.6759(2)nm, b=1.4131(5)nm, c=1.1650(4)nm, V=1.1128(6)n m3, Z=4, Dc=1.578g/cm3, F(000)=560, s=1.069, μ(MoKα)=0.318mm-1. The final R and Wr are 0.0312 and 0.0833, respectively. The title compound is an ionic compound and its structure unit consists of two aminoguanidium cations, one sulfate anion and one crystal water molecule, which are interconnected by electrostatic forces and hydrogen bond s into net structure, making the title compound very stable. Under a linear heat ingrate, the thermal decomposition processes of (AG)2SO4·H2O have one en dothermal dehydration stage, one melting process and one exothermic decomposition stage at 50-400℃, and can evolve abundant gas products.

  4. Diammonium tricadmium tris(sulfate dihydroxide dihydrate

    Directory of Open Access Journals (Sweden)

    Xin Yin

    2011-05-01

    Full Text Available The title compound, (NH42Cd3(SO43(OH2(H2O2, has been obtained serendipitously. It is isotypic with the heavier alkali analogues M2Cd3(SO43(OH2(H2O2 (M = K, Rb, Cs. The structure contains two Cd2+ ions, one in a general position and one with site symmetry m. The former Cd2+ ion is coordinated by three O atoms of three SO4 groups, two hydroxide O atoms and one water O atom, the latter Cd2+ ion by four O atoms of four SO4 groups and two hydroxide O atoms, both in a distorted octahedral coordination geometry. This arrangement leads to the formation of a layered framework extending parallel to (100, with the ammonium cations situated in the voids. O—H...O hydrogen bonds involving the water molecules, hydroxide groups and sulfate O atoms, as well as N—H...O hydrogen bonds between ammonium cations and sulfate O atoms consolidate the crystal packing.

  5. Effects of brief and intermediate exposures to sulfate submicron aerosols and sulfate injections on cardiopulmonary function of dogs and tracheal mucous velocity of sheep

    Energy Technology Data Exchange (ETDEWEB)

    Sackner, M.A. (Mount Sinai Medical Center, Miami Beach, FL); Dougherty, R.L.; Chapman, G.A.; Cipley, J.; Perez, D.; Kwoka, M.; Reinhart, M.; Brito, M.; Schreck, R.

    1981-06-01

    Pulmonary mechanics of anesthetized dogs were not changed or were minimally altered by breathing the following compounds as submicron aerosols in concentrations up to 17.3 mg/m/sup 3/ for 7.5 min: (1) sodium chloride (as a control), (2) sodium sulfate, (3) ammonium sulfate, (4) zinc sulfate, (5) zinc ammonium sulfate, (6) ammonium bisulfate, (7) aluminum sulfate, (8) manganese sulfate, (9) nickel sulfate, (10) copper sulfate, (11) ferrous fulfate, and (12) ferric sulfate. Submicron aerosols of these compounds in concentrations of 4.1 to 8.8 mg/m/sup 3/, administered for 4 h to anesthetized dogs, did not affect mechanics of breathing, hemodynamics, and arterial blood gases. In conscious sheep, tracheal mucous velocity was not altered by exposure to the submicron aerosols of the sulfate compounds. None of these compounds, injected iv in a dose of 1 mg, had adverse effects on mechanics of breathing, pulmonary and systemic hemodynamics, or arterial blood gases. In 100-mg injections, zinc sulfate and zinc ammonium sulfate produced a fall in cardiac output, systemic hypotension, hypoxemia, and metabolic acidosis. Copper sulfate at this dose produced pulmonary hypertension, a fall in cardiac output, hypoxemia, respiratory acidosis, and a decrease of specific total respiratory conductance. It is concluded that submicron aerosols of sulfate salts do not have adverse cardiopulmonary effects when administered in high concentrations for up to 4 h. However, prolonged exposure to high concentrations of zinc sulfate, zinc ammonium sulfate, and copper sulfate aerosols might have adverse cardiopulmonary effects.

  6. Chondroitin sulfate N-acetylgalactosaminyltransferase-1 (CSGalNAcT-1) involved in chondroitin sulfate initiation: Impact of sulfation on activity and specificity.

    Science.gov (United States)

    Gulberti, Sandrine; Jacquinet, Jean-Claude; Chabel, Matthieu; Ramalanjaona, Nick; Magdalou, Jacques; Netter, Patrick; Coughtrie, Michael W H; Ouzzine, Mohamed; Fournel-Gigleux, Sylvie

    2012-04-01

    Glycosaminoglycan (GAG) assembly initiates through the formation of a linkage tetrasaccharide region serving as a primer for both chondroitin sulfate (CS) and heparan sulfate (HS) chain polymerization. A possible role for sulfation of the linkage structure and of the constitutive disaccharide unit of CS chains in the regulation of CS-GAG chain synthesis has been suggested. To investigate this, we determined whether sulfate substitution of galactose (Gal) residues of the linkage region or of N-acetylgalactosamine (GalNAc) of the disaccharide unit influences activity and specificity of chondroitin sulfate N-acetylgalactosaminyltransferase-1 (CSGalNAcT-1), a key glycosyltransferase of CS biosynthesis. We synthesized a series of sulfated and unsulfated analogs of the linkage oligosaccharide and of the constitutive unit of CS and tested these molecules as potential acceptor substrates for the recombinant human CSGalNAcT-1. We show here that sulfation at C4 or C6 of the Gal residues markedly influences CSGalNAcT-1 initiation activity and catalytic efficiency. Kinetic analysis indicates that CSGalNAcT-1 exhibited 3.6-, 1.6-, and 2.2-fold higher enzymatic efficiency due to lower K(m) values toward monosulfated trisaccharides substituted at C4 or C6 position of Gal1, and at C6 of Gal2, respectively, compared with the unsulfated oligosaccharide. This highlights the critical influence of Gal substitution on both CSGalNAcT-1 activity and specifity. No GalNAcT activity was detected toward sulfated and unsulfated analogs of the CS constitutive disaccharide (GlcA-β1,3-GalNAc), indicating that CSGalNAcT-1 was involved in initiation but not in elongation of CS chains. Our results strongly suggest that sulfation of the linkage region acts as a regulatory signal in CS chain initiation.

  7. Utilization of sulfate additives in biomass combustion: fundamental and modeling aspects

    DEFF Research Database (Denmark)

    Wu, Hao; Jespersen, Jacob Boll; Grell, Morten Nedergaard

    2013-01-01

    Sulfates, such as ammonium sulfate, aluminum sulfate and ferric sulfate, are effective additives for converting the alkali chlorides released from biomass combustion to the less harmful alkali sulfates. Optimization of the use of these additives requires knowledge on their decomposition rate and ...

  8. 去氢表雄酮的生理活性及其微生物转化的研究进展%Research progress of physiological activity and microbial transformation of dehydroepiandrosterone

    Institute of Scientific and Technical Information of China (English)

    闫尚和

    2014-01-01

    In this paper,to understand the physiological activity and microbial transformation of dehydroepiandrosterone,and to lay the foundation for the research and development of new type,high-efficiency and harmfulless steroidal compounds,the research progresses of physiological activity and microbial transformation of dehydroepiandrosterone from 1991 to 2013 in PUBMED database were summarized. Conclusion:Dehydroepiandrosterone had unique physiological activity on the antineoplastic, protection of the central nervous system,regulation and other aspectes.And we could product a series of new type and high-efficiency steroidal compounds by using microbial transformation process.It provided a good theoretical and applied foundation for the development of new drugs.%为了解去氢表雄酮的生理活性及其微生物转化,为新型高效低毒的甾体化合物的研发奠定基础,本文综述了PUBMED 数据库1991-2013年去氢表雄酮的生理活性及其微生物转化的研究进展。得出结论:去氢表雄酮在抗肿瘤、保护中枢神经系统、调节等方面均有独特的生理活性;而且可利用微生物转化法制备出一系列新型、高效的甾体化合物,为新药的开发提供了良好的理论和应用基础。

  9. Serum dehydroepiandrosterone sulphate concentration is not a predictive factor in IVF outcomes before the first cycle of GnRH agonist administration in women with normal ovarian reserve.

    Directory of Open Access Journals (Sweden)

    Michał Kunicki

    Full Text Available The aim of our study was to determine whether serum dehydroepiandrosterone sulphate (DHEAS concentration and the models incorporating it could help clinicians to predict IVF outcomes in women with normal ovarian reserve undergoing their first long protocol.We performed a retrospective analysis of 459 women undergoing cycles of intracytoplasmic sperm injection (ICSI for the first time in a long GnRH agonist protocol.Embryo transfer was performed in 407 women (88.7%. The fertilisation rate was 78.6%. The clinical pregnancy rate was 44.8% per started cycle and 50.6% per embryo transfer. Our univariate model revealed that the best predictors of clinical pregnancy were the number of mature oocytes, the number of embryos transferred and the number of good quality embryos, account for the clinical parameters that reflect ovarian reserve the best being AMH level and AFC. DHEAS did not predict clinical pregnancy (OR 1.001, 95% CI, 0.999-1.004. After adjusting for the number of embryos transferred and class of embryos in a multivariate model, the best predictors were age (OR 0.918, 95% CI, 0.867-0.972 and AFC (OR 1.022, 95% CI, 0.992-1.053. Serum DHEAS levels were positively correlated with AFC (r = 0.098, P<0.039 and testosterone levels (r = 0.371, P<0.001, as well as the number of mature oocytes (r = 0.109, P<0.019; serum DHEAS levels were negatively correlated with age (r = -0.220, P<0.001, follicle-stimulating hormone (FSH, (r = -0.116, P<0.015 and sex hormone-binding globulin (SHBG, (r = -0.193, P<0.001.DHEAS concentration (in addition to the known factors of ovarian reserve does not predict clinical pregnancy in women with normal ovarian reserve who are undergoing ICSI.

  10. Dehydroepiandrosterone Activation of G-protein-coupled Estrogen Receptor Rapidly Stimulates MicroRNA-21 Transcription in Human Hepatocellular Carcinoma Cells.

    Science.gov (United States)

    Teng, Yun; Radde, Brandie N; Litchfield, Lacey M; Ivanova, Margarita M; Prough, Russell A; Clark, Barbara J; Doll, Mark A; Hein, David W; Klinge, Carolyn M

    2015-06-19

    Little is known about the regulation of the oncomiR miR-21 in liver. Dehydroepiandrosterone (DHEA) regulates gene expression as a ligand for a G-protein-coupled receptor and as a precursor for steroids that activate nuclear receptor signaling. We report that 10 nm DHEA increases primary miR-21 (pri-miR-21) transcription and mature miR-21 expression in HepG2 cells in a biphasic manner with an initial peak at 1 h followed by a second, sustained response from 3-12 h. DHEA also increased miR-21 in primary human hepatocytes and Hep3B cells. siRNA, antibody, and inhibitor studies suggest that the rapid DHEA-mediated increase in miR-21 involves a G-protein-coupled estrogen receptor (GPER/GPR30), estrogen receptor α-36 (ERα36), epidermal growth factor receptor-dependent, pertussis toxin-sensitive pathway requiring activation of c-Src, ERK1/2, and PI3K. GPER antagonist G-15 attenuated DHEA- and BSA-conjugated DHEA-stimulated pri-miR-21 transcription. Like DHEA, GPER agonists G-1 and fulvestrant increased pri-miR-21 in a GPER- and ERα36-dependent manner. DHEA, like G-1, increased GPER and ERα36 mRNA and protein levels. DHEA increased ERK1/2 and c-Src phosphorylation in a GPER-responsive manner. DHEA increased c-Jun, but not c-Fos, protein expression after 2 h. DHEA increased androgen receptor, c-Fos, and c-Jun recruitment to the miR-21 promoter. These results suggest that physiological concentrations of DHEA activate a GPER intracellular signaling cascade that increases pri-miR-21 transcription mediated at least in part by AP-1 and androgen receptor miR-21 promoter interaction.

  11. Effects of maternal treatment of dehydroepiandrosterone (DHEA) on serum lipid profile and hepatic lipid metabolism-related gene expression in embryonic chickens.

    Science.gov (United States)

    Chen, Juan; Tang, Xue; Zhang, Yuanshu; Ma, Haitian; Zou, Sixiang

    2010-04-01

    Over the last decade, much evidence emerged to suggest that alterations in maternal diets during pregnancy may irreversibly affect aspects of physiological and biochemical functions in the fetus. To explore the effects of maternal dietary treatments with dehydroepiandrosterone (DHEA) on lipid metabolism in the embryo, we investigated serum lipid profile and hepatic lipid metabolism-related gene expression in the maternal and embryonic chicken. Sixteen-week-old pullets were allocated into 3 groups (n=30), and after laying, they were provided with a commercial diet supplemented with DHEA at 0, 20 or 100mg/kg diet. Eggs were collected after DHEA treatment and incubated at 37.5 degrees C and a relative humidity of 60%. Blood and liver samples were collected from hens and embryonic chickens. DHEA treatment resulted in decreased body weight and increased relative liver weight in both maternal and embryonic chickens, while the concentrations of blood triglyceride (TG), total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C) and non-esterified fatty acid (NEFA) were significantly lower in the 20mg DHEA/kg group as compared to the control group during embryonic development. The expression of acetyl CoA carboxylase (ACC) and carnitine palmitoyl transferase I (CPTI) gene was also reduced following treatment with 20mg DHEA/kg at hatching. However, blood TC, and hepatic fatty acid synthase (FAS) and hydroxy methylglutaryl-CoA reductase (HMGR) gene expression were significantly up-regulated in the 100mg DHEA/kg group during embryonic development and hatching. Overall, the results of this study indicate that maternal dietary treatment with DHEA regulates serum lipid metabolism and hepatic gene expression. 2010 Elsevier Inc. All rights reserved.

  12. Pregnenolone and dehydroepiandrosterone as an adjunctive treatment in schizophrenia and schizoaffective disorder: an 8-week, double-blind, randomized, controlled, 2-center, parallel-group trial.

    Science.gov (United States)

    Ritsner, Michael S; Gibel, Anatoly; Shleifer, Tatyana; Boguslavsky, Igor; Zayed, Ahmad; Maayan, Rachel; Weizman, Abraham; Lerner, Vladimir

    2010-10-01

    Pregnenolone (PREG) and dehydroepiandrosterone (DHEA) are reported to have a modulatory effect on neuronal excitability, synaptic plasticity, and response to stress; they are associated with mood regulation and cognitive performance. We investigated the influence of PREG and DHEA on psychotic symptoms and cognitive functioning as an add-on to ongoing antipsychotic treatment of patients with chronic schizophrenia or schizoaffective disorder. This 8-week, double-blind, randomized, placebo-controlled, 2-center study compared 30 mg/d of PREG (PREG-30), 200 mg/d of PREG (PREG-200), 400 mg/d of DHEA, and placebo as an adjunctive treatment of 58 chronic schizophrenia or schizoaffective disorder patients (DSM-IV). The data were collected from February 2005 until June 2007. The outcome measures were symptomatic and neurocognitive changes, functioning, and tolerability as assessed primarily by the Clinical Global Impressions-Severity of Illness scale and the Positive and Negative Syndrome Scale. Analyses are presented for 44 patients who completed 8 weeks of treatment and for 14 noncompleters. Compared with subjects who received placebo, those administered PREG-30 had significant reductions in positive symptom scores and extrapyramidal side effects (EPS) and improvement in attention and working memory performance, whereas subjects treated with PREG-200 did not differ on outcome variable scores for the study period. The general psychopathology severity and general functioning of patients receiving placebo and PREG-30 improved more than that of those subjects treated with DHEA, while EPS improved more in subjects treated with DHEA than in patients receiving placebo. Negative symptoms and akathisia were not significantly benefited by any treatment. The administration of PREG and DHEA was well tolerated. Low-dose PREG augmentation demonstrated significant amelioration of positive symptoms and EPS and improvement in attention and working memory performance of schizophrenia and

  13. The effect of dehydroepiandrosterone supplementation to symptomatic perimenopausal women on serum endocrine profiles, lipid parameters, and health-related quality of life.

    Science.gov (United States)

    Barnhart, K T; Freeman, E; Grisso, J A; Rader, D J; Sammel, M; Kapoor, S; Nestler, J E

    1999-11-01

    Dehydroepiandrosterone (DHEA), an androgenic steroid hormone, exhibits an age-related decline. Perimenopausal women have only approximately 50% of peak DHEA levels. Despite limited scientific data, DHEA has gained recognition as a dietary supplement to reduce the symptoms of aging and improve well-being. This randomized, double-blind placebo-controlled trial examined the effects of 50 mg/day of oral DHEA supplementation, for 3 months, on 60 perimenopausal women with complaints of altered mood and well-being. Changes in the serum endocrine profile of women in the DHEA group were significantly greater than the placebo group, including a 242% [95% confidence interval (CI) +60.1, +423.9] increase in DHEAS, a 94.8% (95% CI +34.2, +155.4) increase in testosterone, and a 13.2% (95% CI -27.88, +0.5) decline in cortisol compared to baseline. Women receiving DHEA had a 10.1% (95% CI -15.0, -5.1) decline in high-density lipoprotein and an 18.1% (95% CI -32.2, -3.9) decline in Lp(a) from baseline, but these declines did not significantly differ from women who received placebo. Women receiving DHEA did not have any improvements significantly greater than placebo in the severity of perimenopausal symptoms, mood, dysphoria, libido, cognition, memory, or well-being. DHEA supplementation significantly effects the endocrine profile, may affect the lipid profile, but does not improve perimenopausal symptoms or well-being compared to placebo.

  14. Ontogenetic Change in the Regional Distribution of Dehydroepiandrosterone-Synthesizing Enzyme and the Glucocorticoid Receptor in the Brain of the Spiny Mouse (Acomys cahirinus).

    Science.gov (United States)

    Quinn, Tracey A; Ratnayake, Udani; Dickinson, Hayley; Castillo-Melendez, Margie; Walker, David W

    2016-01-01

    The androgen dehydroepiandrosterone (DHEA) has trophic and anti-glucocorticoid actions on brain growth. The adrenal gland of the spiny mouse (Acomys cahirinus) synthesizes DHEA. The aim of this study was to determine whether the brain of this precocial species is also able to produce DHEA de novo during fetal, neonatal and adult life. The expression of P450c17 and cytochrome b5 (Cytb5), the enzyme and accessory protein responsible for the synthesis of DHEA, was determined in fetal, neonatal and adult brains by immunocytochemistry, and P450c17 bioactivity was determined by the conversion of pregnenolone to DHEA. Homogenates of fetal brain produced significantly more DHEA after 48 h in culture (22.46 ± 2.0 ng/mg tissue) than adult brain homogenates (5.04 ± 2.0 ng/mg tissue; p < 0.0001). P450c17 and Cytb5 were co-expressed in fetal neurons but predominantly in oligodendrocytes and white matter tracts in the adult brain. Because DHEA modulates glucocorticoids actions, the expression of the glucocorticoid receptor (GR) was also determined. In the brainstem, medulla, midbrain, and cerebellum, the predominant GR localization changed from neurons in the fetal brain to oligodendrocytes and white matter tracts in the adult brain. The change of expression of P450c17, Cytb5 and GR proteins with cell type, brain region and developmental age indicates that DHEA is an endogenous neurosteroid in this species that may have important trophic and stress-modifying actions during both prenatal and postnatal life.

  15. Sources of variation in plasma corticosterone and dehydroepiandrosterone in the male northern cardinal (Cardinalis cardinalis): I. Seasonal patterns and effects of stress and adrenocorticotropic hormone.

    Science.gov (United States)

    Fokidis, H Bobby

    2016-09-01

    The secretion of steroids from the adrenal gland is a classic endocrine response to perturbations that can affect homeostasis. During an acute stress response, glucocorticoids (GC), such as corticosterone (CORT), prepare the metabolic physiology and cognitive abilities of an animal in a manner that promotes survival during changing conditions. Although GC functions during stress are well established, much less is understood concerning how adrenal androgens, namely dehydroepiandrosterone (DHEA) are influenced by stress. I conducted three field studies (one experimental and two descriptive) aimed at identifying how both CORT and DHEA secretion in free-living male northern cardinals (Cardinalis cardinalis), vary during acute stress; across different circulations (brachial vs. jugular); in response to ACTH challenge; and during the annual cycle. As predicted, restraint stress increased plasma CORT, but unexpectedly DHEA levels decreased, but the latter effect was only seen for blood sampled from the jugular vein, and not the brachial. The difference in DHEA between circulations may result from increased neural uptake of DHEA during stress. Injection with exogenous adrenocorticotropic hormone (ACTH) increased CORT concentrations, but failed to alter DHEA levels, thus suggesting ACTH is not a direct regulator of DHEA. Monthly field sampling revealed distinct seasonal patterns to both initial and restraint stress CORT and DHEA levels with distinct differences in the steroid milieu between breeding and non-breeding seasons. These data suggest that the CORT response to stress remains relatively consistent, but DHEA secretion is largely independent of the response by CORT. Although CORT functions have been well-studied in wild animals, little research exists for the role of DHEA and their variable relationship sets the stage for future experimental research addressing steroid stress responses.

  16. Sources of variation in plasma corticosterone and dehydroepiandrosterone in the male northern cardinal (Cardinalis cardinalis): II. Effects of urbanization, food supplementation and social stress.

    Science.gov (United States)

    Wright, Sarah; Fokidis, H Bobby

    2016-09-01

    Perturbations in an organism's environment can induce significant shifts in hormone secretory patterns. In this context, the glucocorticoid (GC) steroids secreted by the adrenal cortex have received much attention from ecologists and behaviorists due to their role in the vertebrate stress response. Adrenal GCs, such as corticosterone (CORT), are highly responsive to instability in environmental and social conditions. However, little is understood about how adrenal dehydroepiandrosterone (DHEA) is influenced by changing conditions. We conducted field experiments to determine how circulating CORT and DHEA vary during restraint stress in the male northern cardinals (Cardinalis cardinalis). Specifically, we examined how four different changes in the physical (urbanization and food availability) and social (territorial conflict, distress of a mate) environment affect CORT and DHEA levels. The majority of cardinals responded to restraint stress by increasing and decreasing CORT and DHEA, respectively, however this depended on sampling context. Cardinals sampled from urban habitats had both lower initial and restraint stress CORT concentrations, but a comparable DHEA pattern to those sampled from a forest. Supplementing food to territorial males did not alter circulating initial DHEA or CORT concentrations nor did it change the response to restraint stress when compared to unsupplemented controls. Exposing cardinals to varying durations of song playback, which mimics a territorial intrusion, did not affect CORT levels, but did attenuate the DHEA response to restraint stress. Examining a larger dataset of males captured before, after or at the same time as their female mate, allowed us to address how the stress of a captured mate affected the male's CORT and DHEA response. Males showed elevated initial and restraint CORT and DHEA when their female mate was captured first. Taken together, these data demonstrate that both CORT and DHEA secretion patterns depends on

  17. Effects of Ning Shen Ling Granule(宁神灵冲剂)and Dehydroepiandrosterone on Cognitive Function in Mice Undergoing Chronic Mild Stress

    Institute of Scientific and Technical Information of China (English)

    ZHANG Xiao; DONG Yi-long; YANG Nan; LIU Yan-yong; GAO Rui-feng; ZUO Ping-ping

    2007-01-01

    Objective:To investigate the changes of spontaneous and cognitive behavior,and cholinergic M receptors in the brain of mice subjected to chronic mild stress (CMS),and to determine the effect of Ning Shen Ling Granule (宁神灵冲剂,NSL) and dehydroepiandrosterone (DHEA) on them.Methods:CMS model mice were established by applying stress every day for 3 consecutive weeks with 7 kinds of unforeseeable stress sources,and they were medicated for 1 week beginning at the 3rd week of modeling.The changes in behavior were determined by Morris Water Maze and spontaneous movement test,and M-receptor binding activity in cerebral cortex,hippocampus and hypothalamus were measured by radioactive ligand assay with 3H-QNB.Results:(1)The spontaneous movement in CMS model mice was significantly reduced,with the latency for searching platform in Morris Water Maze obviously prolonged (P<0.01),and these abnormal changes in behavior were improved in those treated with NSL and DHEA.(2)The binding ability of M-receptor in cerebral cortex and hippocampus of CMS mice was significantly decreased as compared with those in the control group (P<0.05),but could be restored to the normal level after intervention with NSL or DHEA.Conclusion:The decline of spontaneous movement and spatial learning and memory ability could be induced in animals by chronic mild stress,and that may be related to the low activity of central cholinergic M-receptors.Both NSL and DHEA could effectively alleviate the above-mentioned changes.

  18. Alternative mechanism for anti-obesity effect of dehydroepiandrosterone: possible contribution of 11β-hydroxysteroid dehydrogenase type 1 inhibition in rodent adipose tissue.

    Science.gov (United States)

    Tagawa, Noriko; Minamitani, Erika; Yamaguchi, Yuko; Kobayashi, Yoshiharu

    2011-12-20

    Dehydroepiandrosterone (DHEA) has been suggested to have an anti-obesity effect; however, the mechanism underlying this effect remains unclear. The effect of DHEA on adipocytes opposes that of glucocorticoids, which potentiate adipogenesis. The key to the intracellular activation of glucocorticoids in adipocytes is 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), which catalyses the production of active glucocorticoids (cortisol in humans and corticosterone in rodents) from an inactive 11-keto form (cortisone in humans and 11-dehydrocorticosterone in rodents). In humans and rodents, intracellular glucocorticoid reactivation is exaggerated in obese adipose tissue. Using differentiated 3T3-L1 adipocytes, we demonstrated that DHEA inhibited about 15.6% of 11β-HSD1 activity at a concentration of 1 μM within 10min. Inhibition was also observed in a cell-free system composed of microsomes prepared from rat adipose tissue and NADPH, a coenzyme of 11β-HSD1. A kinetic study revealed that DHEA acted as a non-competitive inhibitor of 11β-HSD1. Moreover, conversion from DHEA to estrogens was not observed by sensitive semi-micro HPLC equipped with electrochemical detector. These results indicate that the inhibition of 11β-HSD1 by DHEA depends on neither the transcriptional pathway nor the nonspecific manner. This is the first demonstration that the anti-obesity effect of DHEA is exerted by non-transcriptional inhibition of 11β-HSD1 in rodent adipocytes. Copyright © 2011 Elsevier Inc. All rights reserved.

  19. Upper tropospheric ice sensitivity to sulfate geoengineering

    Science.gov (United States)

    Visioni, Daniele; Pitari, Giovanni; Mancini, Eva

    2017-04-01

    In light of the Paris Agreement which aims to keep global warming under 2 °C in the next century and considering the emission scenarios produced by the IPCC for the same time span, it is likely that to remain below that threshold some kind of geoengineering technique will have to be deployed. Amongst the different methods, the injection of sulfur into the stratosphere has received much attention considering its effectiveness and affordability. Aside from the rather well established surface cooling sulfate geoengineering (SG) would produce, the investigation on possible side-effects of this method is still ongoing. For instance, some recent studies have investigated the effect SG would have on upper tropospheric cirrus clouds, expecially on the homogenous freezing mechanisms that produces the ice particles (Kuebbeler et al., 2012). The goal of the present study is to better understand the effect of thermal and dynamical anomalies caused by SG on the formation of ice crystals via homogeneous freezing by comparing a complete SG simulation with a RCP4.5 reference case and with a number of sensitivity studies where atmospheric temperature changes in the upper tropospheric region are specified in a schematic way as a function of the aerosol driven stratospheric warming and mid-lower tropospheric cooling. These changes in the temperature profile tend to increase atmospheric stabilization, thus decreasing updraft and with it the amount of water vapor available for homogeneous freezing in the upper troposphere. However, what still needs to be assessed is the interaction between this dynamical effect and the thermal effects of tropospheric cooling (which would increase ice nucleation rates) and stratospheric warming (which would probably extend to the uppermost troposphere via SG aerosol gravitational settling, thus reducing ice nucleation rates), in order to understand how they combine together. Changes in ice clouds coverage could be important for SG, because cirrus ice

  20. A radioimmunoassay for measurement of thyroxine sulfate

    Energy Technology Data Exchange (ETDEWEB)

    Chopra, I.J.; Santini, F.; Hurd, R.E.; Chua Teco, G.N. (Univ. of California Center for the Health Sciences, Los Angeles (United States))

    1993-01-01

    A highly sensitive, specific, and reproducible RIA has been developed to measure T[sub 4] sulfate (T[sub 4]S) in ethanol extracts of serum. rT[sub 3] sulfate (rT[sub 3]S) cross-reacted 7.1%, and T[sub 3]S cross-reacted 0.59% in the RIA; T[sub 4], T[sub 3], rT[sub 3] and 3,3[prime]-diiodothyronine cross-reacted 0.004% or less. The recovery of nonradioactive T[sub 4]S added to serum averaged 95%. The detection threshold of the RIA was 18 pmol/L. The coefficient of variation averaged 6.9% within an assay and 12% between assays. T[sub 4]S was bound by T[sub 4]-binding globulin and albumin in serum. The free fraction of T[sub 4]S in four normal sera averaged 0.06% compared to a value of 0.03% for T[sub 4] (P < 0.001). The serum concentration of T[sub 4]S was (mean [+-] SE) 19 [+-] 1.2 pmol/L in normal subjects, 33 [+-] 10 in hyperthyroid patients with Graves disease, 42 [+-] 15 in hypothyroid patients, 34 [+-] 6.9 in patients with systematic nonthyroidal illnesses, 21 [+-] 4.3 in pregnant women at 15-40 weeks gestation, and 245 [+-] 26 in cord blood sera of newborns; the value in the newborn was significantly different from normal (P < 0.001). Administration of sodium ipodate (Oragrafin; 3 g, orally) to hyperthyroid patients was associated with a transient increase in serum T[sub 4]S. The T[sub 4]S content of the thyroid gland was less than 1/4000th that of T[sub 4]. We conclude that (1) T[sub 4]S is a normal component of human serum, and its levels are markedly increased in newborn serum and amniotic fluid; and (2) the sulfation pathway plays an important role in the metabolism of T[sub 4] in man. 28 refs., 4 figs., 2 tabs.

  1. The platelet glycoprotein thrombospondin binds specifically to sulfated glycolipids.

    Science.gov (United States)

    Roberts, D D; Haverstick, D M; Dixit, V M; Frazier, W A; Santoro, S A; Ginsburg, V

    1985-08-05

    The human platelet glycoprotein thrombospondin (TSP) binds specifically and with high affinity to sulfatides (galactosylceramide-I3-sulfate). Binding of 125I-TSP to lipids from sheep and human erythrocytes and human platelets resolved on thin layer chromatograms indicates that sulfatides are the only lipids in the membrane which bind TSP. Binding to less than 2 ng of sulfatide could be detected. TSP failed to bind to other purified lipids including cholesterol 3-sulfate, phospholipids, neutral glycolipids, and gangliosides. Binding of 125I-TSP was inhibited by unlabeled TSP, by low pH, and by reduction of intersubunit disulfide bonds with dithiothreitol. A monoclonal antibody against TSP (A2.5), which inhibits hemagglutination and agglutination of fixed activated platelets by TSP, strongly inhibited TSP binding to sulfatides. A second monoclonal antibody (C6.7), which inhibits hemagglutination and aggregation of thrombin-activated live platelets, weakly inhibited sulfatide binding. Binding was inhibited by high ionic strength and by some monosaccharide sulfates including methyl-alpha-D-GlcNAc-3-sulfate. Neutral sugars did not inhibit. Fucoidan, a sulfated fucan, strongly inhibited binding with 50% inhibition at 0.3 micrograms/ml fucoidan. Other sulfated polysaccharides including heparin and dextran sulfates were good inhibitors, whereas hyaluronic acid and keratan sulfate were very weak.

  2. Quantitative Analysis of Sulfate in Water by Indirect EDTA Titration

    Science.gov (United States)

    Belle-Oudry, Deirdre

    2008-01-01

    The determination of sulfate concentration in water by indirect EDTA titration is an instructive experiment that is easily implemented in an analytical chemistry laboratory course. A water sample is treated with excess barium chloride to precipitate sulfate ions as BaSO[subscript 4](s). The unprecipitated barium ions are then titrated with EDTA.…

  3. Transmission spectra study of sulfate substituted potassium dihydrogen phosphate

    KAUST Repository

    LI, LIANG

    2013-04-18

    Potassium dihydrogen phosphate (KDP) crystals with different amounts of sulfate concentration were grown and the transmittance spectrum was studied. A crystal with high sulfate replacement density exhibits heavy absorption property in the ultraviolet region which confirms and agrees well with former results. © 2013 Astro Ltd.

  4. Differential Expression of Specific Dermatan Sulfate Domains in Renal Pathology

    NARCIS (Netherlands)

    Lensen, J.F.M.; Vlag, J. van der; Versteeg, E.M.M.; Wetzels, J.F.M.; Heuvel, L.P.W.J. van den; Berden, J.H.M.; Kuppevelt, T.H. van; Rops, A.

    2015-01-01

    Dermatan sulfate (DS), also known as chondroitin sulfate (CS)-B, is a member of the linear polysaccharides called glycosaminoglycans (GAGs). The expression of CS/DS and DS proteoglycans is increased in several fibrotic renal diseases, including interstitial fibrosis, diabetic nephropathy, mesangial

  5. Novel Thermally Stable Poly (vinyl chloride) Composites for Sulfate Removal

    Science.gov (United States)

    BaCO3 dispersed PVC composites were prepared through a polymer re-precipitation method. The composites were tested for sulfate removal using rapid small scale column test (RSSCT) and found to significantly reduce sulfate concentration. The method was extended to synthe...

  6. Biological processes for the production of aryl sulfates

    DEFF Research Database (Denmark)

    2016-01-01

    The present invention generally relates to the field of biotechnology as it applies to the production of aryl sulfates using polypeptides or recombinant cells comprising said polypeptides. More particularly, the present invention pertains to polypeptides having aryl sulfotransferase activity......, recombinant host cells expressing same and processes for the production of aryl sulfates employing these polypeptides or recombinant host cells....

  7. Reductive and sorptive properties of sulfate green rust (GRSO4)

    DEFF Research Database (Denmark)

    Nedel, Sorin

    The Fe(II), Fe(III) hydroxide containing sulfate in its structure, called sulfate green rust (GRSO4), can effectively reduce and convert contaminants to less mobile and less toxic forms. However, the ability of GRSO4 to remove positively charged species from solution, via sorption, is very limited...

  8. 21 CFR 520.110 - Apramycin sulfate soluble powder.

    Science.gov (United States)

    2010-04-01

    ...) caused by strains of E. coli sensitive to apramycin. (2) It is administered for 7 days in drinking water... sulfate soluble powder. (a) Specifications. A water soluble powder used to make a medicated drinking water containing apramycin sulfate equivalent to 0.375 gram of apramycin activity per gallon of drinking water....

  9. 21 CFR 173.385 - Sodium methyl sulfate.

    Science.gov (United States)

    2010-04-01

    ... Specific Usage Additives § 173.385 Sodium methyl sulfate. Sodium methyl sulfate may be present in pectin in accordance with the following conditions. (a) It is present as the result of methylation of pectin by....1 percent by weight of the pectin....

  10. Serum Indoxyl Sulfate Associates with Postangioplasty Thrombosis of Dialysis Grafts.

    Science.gov (United States)

    Wu, Chih-Cheng; Hsieh, Mu-Yang; Hung, Szu-Chun; Kuo, Ko-Lin; Tsai, Tung-Hu; Lai, Chao-Lun; Chen, Jaw-Wen; Lin, Shing-Jong; Huang, Po-Hsun; Tarng, Der-Cherng

    2016-04-01

    Hemodialysis vascular accesses are prone to recurrent stenosis and thrombosis after endovascular interventions.In vitro data suggest that indoxyl sulfate, a protein-bound uremic toxin, may induce vascular dysfunction and thrombosis. However, there is no clinical evidence regarding the role of indoxyl sulfate in hemodialysis vascular access. From January 2010 to June 2013, we prospectively enrolled patients undergoing angioplasty for dialysis access dysfunction. Patients were stratified into tertiles by baseline serum indoxyl sulfate levels. Study participants received clinical follow-up at 6-month intervals until June 2014. Primary end points were restenosis, thrombosis, and failure of vascular access. Median follow-up duration was 32 months. Of the 306 patients enrolled, 262 (86%) had symptomatic restenosis, 153 (50%) had access thrombosis, and 25 (8%) had access failure. In patients with graft access, free indoxyl sulfate tertiles showed a negative association with thrombosis-free patency (thrombosis-free patency rates of 54%, 38%, and 26% for low, middle, and high tertiles, respectively;P=0.001). Patients with graft thrombosis had higher free and total indoxyl sulfate levels. Using multivariate Cox regression analysis, graft thrombosis was independently predicted by absolute levels of free indoxyl sulfate (hazard ratio=1.14;P=0.01) and free indoxyl sulfate tertiles (high versus low, hazard ratio=2.41;P=0.001). Results of this study provide translational evidence that serum indoxyl sulfate is a novel risk factor for dialysis graft thrombosis after endovascular interventions.

  11. Sulfation of ractopamine and salbutamol by the human cytosolic sulfotransferases.

    Science.gov (United States)

    Ko, Kyounga; Kurogi, Katsuhisa; Davidson, Garrett; Liu, Ming-Yih; Sakakibara, Yoichi; Suiko, Masahito; Liu, Ming-Cheh

    2012-09-01

    Feed additives such as ractopamine and salbutamol are pharmacologically active compounds, acting primarily as β-adrenergic agonists. This study was designed to investigate whether the sulfation of ractopamine and salbutamol may occur under the metabolic conditions and to identify the human cytosolic sulfotransferases (SULTs) that are capable of sulfating two major feed additive compounds, ractopamine and salbutamol. A metabolic labelling study showed the generation and release of [(35)S]sulfated ractopamine and salbutamol by HepG2 human hepatoma cells labelled with [(35)S]sulfate in the presence of these two compounds. A systematic analysis using 11 purified human SULTs revealed SULT1A3 as the major SULT responsible for the sulfation of ractopamine and salbutamol. The pH dependence and kinetic parameters were analyzed. Moreover, the inhibitory effects of ractopamine and salbutamol on SULT1A3-mediated dopamine sulfation were investigated. Cytosol or S9 fractions of human lung, liver, kidney and small intestine were examined to verify the presence of ractopamine-/salbutamol-sulfating activity in vivo. Of the four human organs, the small intestine displayed the highest activity towards both compounds. Collectively, these results imply that the sulfation mediated by SULT1A3 may play an important role in the metabolism and detoxification of ractopamine and salbutamol.

  12. Genesis and solution chemistry of acid sulfate soils in Thailand

    NARCIS (Netherlands)

    Breemen, van N.

    1976-01-01

    To study short-term and long-term chemical processes in periodically flooded acid sulfate soils in the Bangkok Plain and in various smaller coastal plains along the Gulf of Thailand, 16 acid sulfate soils and one non-acid marine soil were examined for distribution of iron-sulfur compounds, elemental

  13. Sulfate reduction at low pH in organic wastewaters

    NARCIS (Netherlands)

    Lopes, S.I.C.

    2007-01-01

    The objective of the research described in this thesis was to investigate the operational window of dissimilatory sulfate reduction at low pH (6, 5 and 4) during the acidification of organic wastewaters. High sulfate reduction efficiencies at low pH are desirable for a more sustainable operation of

  14. Genesis and solution chemistry of acid sulfate soils in Thailand

    NARCIS (Netherlands)

    Breemen, van N.

    1976-01-01

    To study short-term and long-term chemical processes in periodically flooded acid sulfate soils in the Bangkok Plain and in various smaller coastal plains along the Gulf of Thailand, 16 acid sulfate soils and one non-acid marine soil were examined for distribution of iron-sulfur compounds, elemental

  15. Catalytic synthesis of sulfated polysaccharides I: Characterization of chemical structure.

    Science.gov (United States)

    Wang, Junlong; Yang, Wen; Yang, Ting; Zhang, Xiaonuo; Zuo, Yuan; Tian, Jia; Yao, Jian; Zhang, Ji; Lei, Ziqiang

    2015-03-01

    In the present study, sulfated derivatives of Artemisia sphaerocephala polysaccharide (SASP) with high degree of substitution (DS) were synthesized by using 4-dimethylaminopyridine (DMAP)/dimethylcyclohexylcarbodiimide (DCC) as catalyst in homogeneous conditions. It was found that DMAP/DCC showed marked improvement in DS of sulfated samples. Compared to sulfated derivatives without catalyst, the DS of SASP increased from 0.91 to 1.28 with an increment in dosage of DMAP from 0 to 10 mg. The influence of DMAP/DCC on the DS of sulfated derivatives was depended on the content of DMAP. The effect of DMAP might be due to its strong coordination to the hydroxy group. The results of FT-IR and X-ray photoelectron spectroscopy (XPS) indicated that SO3- group (S6+, binding energy of 172.3 eV) was widely present in sulfated polysaccharide molecules. 13C NMR results indicated that C-6 substitution was predominant for sulfated polysaccharide when compared with other positions. In the sulfation reaction, a sharp decrease in MW was observed. DMAP/DCC was an effective catalyst system in sulfated modification of polysaccharide.

  16. Structural characterization and bioactivities of sulfated polysaccharide from Monostroma oxyspermum.

    Science.gov (United States)

    Seedevi, Palaniappan; Moovendhan, Meivelu; Sudharsan, Sadhasivam; Vasanthkumar, Shanmugam; Srinivasan, Alagiri; Vairamani, Shanmugam; Shanmugam, Annaian

    2015-01-01

    Sulfated polysaccharide was isolated from Monostroma oxyspermum through hot water extraction, anion-exchange and gel permeation column chromatography. The sulfated polysaccharide contained 92% of carbohydrate, 0% of protein, 7.8% of uronic acid, 22% of ash and 33% of moisture respectively. The elemental composition was analyzed using CHNS/O analyzer. The molecular weight of sulfated polysaccharide determined through PAGE was found to be as 55 kDa. Monosaccharides analysis revealed that sulfated polysaccharide was composed of rhamnose, fructose, galactose, xylose, and glucose. The structural features of sulfated polysaccharide were analyzed by NMR spectroscopy. Further the sulfated polysaccharide showed total antioxidant and DPPH free radical scavenging activity were as 66.29% at 250 μg/ml and 66.83% at 160 μg/ml respectively. The sulfated polysaccharide also showed ABTS scavenging ability and reducing power were as 83.88% at 125 μg/ml and 15.81% at 400 μg/ml respectively. The anticoagulant activity was determined for human plasma with respect to Activated Partial Thromboplastin Time (APTT) and Prothrombin Time (PT) was 20.09 IU and 1.79 IU at 25 μg/ml respectively. These results indicated that the sulfated polysaccharide from M. oxyspermum had potent antioxidant and anticoagulant activities.

  17. Ovarian carcinoma cells synthesize both chondroitin sulfate and heparan sulfate cell surface proteoglycans that mediate cell adhesion to interstitial matrix.

    Science.gov (United States)

    Kokenyesi, R

    Metastatic ovarian carcinoma metastasizes by intra-peritoneal, non-hematogenous dissemination. The adhesion of the ovarian carcinoma cells to extracellular matrix components, such as types I and III collagen and cellular fibronectin, is essential for intra-peritoneal dissemination. The purpose of this study was to determine whether cell surface proteoglycans (a class of matrix receptors) are produced by ovarian carcinoma cells, and whether these proteoglycans have a role in the adhesion of ovarian carcinoma cells to types I and III collagen and fibronectin. Proteoglycans were metabolically labeled for biochemical studies. Both phosphatidylinositol-anchored and integral membrane-type cell surface proteoglycans were found to be present on the SK-OV-3 and NIH:OVCAR-3 cell lines. Three proteoglycan populations of differing hydrodynamic size were detected in both SK-OV-3 and NIH:OVCAR-3 cells. Digestions with heparitinase and chondroitinase ABC showed that cell surface proteoglycans of SK-OV-3 cells had higher proportion of chondroitin sulfate proteoglycans (75:25 of chondroitin sulfate:heparan sulfate ratio), while NIH:OVCAR-3 cells had higher proportion of heparan sulfate proteoglycans (10:90 of chondroitin sulfate:heparan sulfate ratio). RT-PCR indicated the synthesis of a unique assortment of syndecans, glypicans, and CD44 by the two cell lines. In adhesion assays performed on matrix-coated titer plates both cell lines adhered to types I and III collagen and cellular fibronectin, and cell adhesion was inhibited by preincubation of the matrix with heparin, heparan sulfate, chondroitin sulfate, dermatan sulfate, or chondroitin glycosaminoglycans. Treatment of the cells with heparitinase, chondroitinase ABC, or methylumbelliferyl xyloside also interfered with adhesion confirming the role of both heparan sulfate and chondroitin sulfate cell surface proteoglycans as matrix receptors on ovarian carcinoma cells.

  18. Effects of chlorate on the sulfation process of Trypanosoma cruzi glycoconjugates. Implication of parasite sulfates in cellular invasion.

    Science.gov (United States)

    Ferrero, Maximiliano R; Soprano, Luciana L; Acosta, Diana M; García, Gabriela A; Esteva, Mónica I; Couto, Alicia S; Duschak, Vilma G

    2014-09-01

    Sulfation, a post-translational modification which plays a key role in various biological processes, is inhibited by competition with chlorate. In Trypanosoma cruzi, the agent of Chagas' disease, sulfated structures have been described as part of glycolipids and we have reported sulfated high-mannose type oligosaccharides in the C-T domain of the cruzipain (Cz) glycoprotein. However, sulfation pathways have not been described yet in this parasite. Herein, we studied the effect of chlorate treatment on T. cruzi with the aim to gain some knowledge about sulfation metabolism and the role of sulfated molecules in this parasite. In chlorate-treated epimastigotes, immunoblotting with anti-sulfates enriched Cz IgGs (AS-enriched IgGs) showed Cz undersulfation. Accordingly, a Cz mobility shift toward higher isoelectric points was observed in 2D-PAGE probed with anti-Cz antibodies. Ultrastructural membrane abnormalities and a significant decrease of dark lipid reservosomes were shown by electron microscopy and a significant decrease in sulfatide levels was confirmed by TLC/UV-MALDI-TOF-MS analysis. Altogether, these results suggest T. cruzi sulfation occurs via PAPS. Sulfated epitopes in trypomastigote and amastigote forms were evidenced using AS-enriched IgGs by immunoblotting. Their presence on trypomastigotes surface was demonstrated by flow cytometry and IF with Cz/dCz specific antibodies. Interestingly, the percentage of infected cardiac HL-1 cells decreased 40% when using chlorate-treated trypomastigotes, suggesting sulfates are involved in the invasion process. The same effect was observed when cells were pre-incubated with dCz, dC-T or an anti-high mannose receptor (HMR) antibody, suggesting Cz sulfates and HMR are also involved in the infection process by T. cruzi.

  19. Preparation and characterization of a chemically sulfated cashew gum polysaccharide

    Energy Technology Data Exchange (ETDEWEB)

    Moura Neto, Erico de; Maciel, Jeanny da S.; Cunha, Pablyana L. R.; Paula, Regina Celia M. de; Feitosa, Judith P.A., E-mail: judith@dqoi.ufc.br [Departamento de Quimica Organica e Inorganica, Universidade Federal do Ceara, Fortaleza (Brazil)

    2011-09-15

    Cashew gum (CG) was sulfated in pyridine:formamide using chlorosulfonic acid as the reagent. Confirmation of sulfation was obtained by Fourier transform infrared (FTIR) spectroscopy through the presence of an asymmetrical S=O stretching vibration at 1259 cm{sup -1}. The degrees of substitution were 0.02, 0.24 and 0.88 determined from the sulfur percentage. 1D and 2D nuclear magnetic resonance (NMR) data showed that the sulfation occurred at primary carbons. An increase of at least 4% of the solution viscosity was observed due to sulfation. The thermal gravimetric curves (TGA) indicate that the derivatives are stable up to ca. 200 deg C. The sulfated CG is compared to carboxymethylated CG in order to verify the possibility of the use of the former in the preparation of polyelectrolyte complexes; the latter is already being used for this application. (author)

  20. Distribution of sulfate between phases in Portland cement clinkers

    Energy Technology Data Exchange (ETDEWEB)

    Taylor, H.F.W.

    1999-08-01

    Sulfate can occur in Portland cement clinkers as alkali sulfates, potassium calcium sulfate (calcium langbeinite), anhydrite, and as a substituent in the major phases, especially alite and belite. Data for the contents in alit and belite are reviewed and relations to bulk clinker composition are discussed. Evidence on sulfate distribution from extraction procedures is similarly considered. A procedure for predicting sulfate distribution from bulk composition is described and tested and potential sources of error in such calculations are discussed. The evidence does not support suggests that, in concrete made with present-day cements and not subjected to an elevated temperature, damage through delayed ettringite formation can occur for reasons connected with the SO{sub 3} present in the clinker.