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Sample records for involving hypothalamic-pituitary-gonadal axis

  1. Hypothalamic-pituitary-gonadal axis involvement in learning and memory and Alzheimer disease: More than Just Estrogen

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    Jeffrey A. Blair

    2015-03-01

    Full Text Available Accumulating studies affirm the effects of age-related endocrine dysfunction on cognitive decline and increasing risk of neurodegenerative diseases. It is well known that estrogen can be protective for cognitive function, and more recently testosterone and luteinizing hormone have also been shown to modulate learning and memory. Understanding the mechanisms underlying hypothalamic-pituitary-gonadal axis associated cognitive dysfunction is crucial for therapeutic advancement. Here, we emphasize that reproductive hormones are influential in maintaining neuronal health and enhancing signaling cascades that lead to cognitive impairment. We summarize and critically evaluate age-related changes in the endocrine system, their implications in the development of Alzheimer’s disease, and the therapeutic potential of endocrine modulation in the prevention of age-related cognitive decline.

  2. Combined effects of androgen anabolic steroids and physical activity on the hypothalamic-pituitary-gonadal axis.

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    Hengevoss, Jonas; Piechotta, Marion; Müller, Dennis; Hanft, Fabian; Parr, Maria Kristina; Schänzer, Wilhelm; Diel, Patrick

    2015-06-01

    Analysing effects of pharmaceutical substances and training on feedback mechanisms of the hypothalamic-pituitary-gonadal axis may be helpful to quantify the benefit of strategies preventing loss of muscle mass, and in the fight against doping. In this study we analysed combined effects of anabolic steroids and training on the hypothalamic-pituitary-gonadal axis. Therefore intact male Wistar rats were dose-dependently treated with metandienone, estradienedione and the selective androgen receptor modulator (SARM) S-1. In serum cortisol, testosterone, 17β-estradiol (E2), prolactin, inhibin B, follicle-stimulating hormone (FSH), luteinizing hormone (LH), Insulin-like growth factor 1 (IGF-1), and thyroxine (T4) concentrations were determined. Six human volunteers were single treated with 1-androstenedione. In addition abusing and clean body builders were analysed. Serum concentrations of inhibin B, IGF-1, cortisol, prolactin, T4, thyroid-stimulating hormone (TSH), testosterone and LH were determined. In rats, administration of metandienone, estradienedione and S-1 resulted in an increase of muscle fiber diameter. Metandienone and estradienedione but not S-1 administration significantly decreases LH and inhibin B serum concentration. Administration of estradienedione resulted in an increase of E2 and S-1 in an increase of cortisol. Single administration of 1-androstenedione in humans decreased cortisol and inhibin B serum concentrations. LH was not affected. In abusing body builders a significantly decrease of LH, TSH and inhibin B and an increase of prolactin, IGF-1 and T4 was detected. In clean body builders only T4 and TSH were affected. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. A study of temporal effects of the model anti-androgen flutamide on components of the hypothalamic-pituitary-gonadal axis in adult fathead minnows

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    U.S. Environmental Protection Agency — The aim of this study was to investigate temporal changes in the hypothalamic-pituitary-gonadal axis of fathead minnow treated with the model androgen receptor (AR)...

  4. Transcriptome analysis revealed the possible regulatory pathways initiating female geese broodiness within the hypothalamic-pituitary-gonadal axis.

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    Hehe Liu

    Full Text Available Geese have the strongest tendency toward broodiness among all poultry. The mechanisms initiating broodiness within the goose hypothalamic-pituitary-gonadal axis (HPGA are still unclear. Here, we reported the transcriptome differences between laying and initial nesting within the HPGA tissues of geese. We constructed a unigene database based on HPGA tissues and identified 128,148 unigenes, 100% of which have been annotated. By using Digital Gene Expression (DGE sequencing, we screened 19, 110, 289, and 211 differentially expressed genes (DEGs in the hypothalamus, pituitary gland, stroma ovarii, and follicles, respectively, between laying and nesting geese. Expression changes of hypocretin (HCRT and pro-opiomelanocortin (POMC in the hypothalamus of nesting geese may cause appetite reduction, which is possibly the first step and a prerequisite to initiate broodiness. In addition to prolactin (PRL, follicle-stimulating hormone (FSH and luteinizing hormone (LH, genes including oxytocin-neurophysin (OXT, chordin-like protein 1 (CHRDL1 and growth hormone (GH, expressed in the pituitary gland, are new candidate molecules that may be involved in broodiness in geese. Heme oxygenase 1 (HMOX1 in the pituitary gland, the proto-oncogene c-Fos (FOS, heat shock protein 90-alpha (HSP90AA, and cyclin-dependent kinase 1 (CDK1 in the ovary that may consolidate and transduce signals regulating the HPGA during broodiness in geese.

  5. Computational Model of the Fathead Minnow Hypothalamic-Pituitary-Gonadal Axis: Incorporating Protein Synthesis in Improving Predictability of Responses to Endocrine Active Chemicals

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    There is international concern about chemicals that alter endocrine system function in humans and/or wildlife and subsequently cause adverse effects. We previously developed a mechanistic computational model of the hypothalamic-pituitary-gonadal (HPG) axis in female fathead minno...

  6. Hypothalamic-pituitary-gonadal axis hormones and cortisol in both menstrual phases of women with chronic fatigue syndrome and effect of depressive mood on these hormones

    OpenAIRE

    Cevik, Remzi; Gur, Ali; Acar, Suat; Nas, Kemal; Sarac, Ayşegül Jale

    2004-01-01

    Abstract Background Chronic fatigue syndrome (CFS) is a disease which defined as medically unexplained, disabling fatigue of 6 months or more duration and often accompanied by several of a long list of physical complaints. We aimed to investigate abnormalities of hypothalamic-pituitary-gonadal (HPG) axis hormones and cortisol concentrations in premenopausal women with CFS and find out effects of depression rate on these hormones. Methods We examined follicle stimulating hormone (FSH), luteini...

  7. Electrotonic Coupling in the Pituitary Supports the Hypothalamic-Pituitary-Gonadal Axis in a Sex Specific Manner

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    Christina Göngrich

    2016-08-01

    Full Text Available Gap junctions are present in many cell types throughout the animal kingdom and allow fast intercellular electrical and chemical communication between neighboring cells. Connexin-36 (Cx36, the major neuronal gap junction protein, synchronizes cellular activity in the brain, but also in other organs. Here we identify a sex-specific role for Cx36 within the hypothalamic-pituitary-gonadal (HPG axis at the level of the anterior pituitary gland (AP. We show that Cx36 is expressed in gonadotropes of the AP sustaining their synchronous activity. Cx36 ablation affects the entire downstream HPG axis in females, but not in males. We demonstrate that Cx36-mediated coupling between gonadotropes in the AP supports gonadotropin-releasing hormone-induced secretion of luteinizing hormone. Furthermore, we provide evidence for negative feedback regulation of Cx36 expression in the AP by estradiol. We thus conclude that hormonally-controlled plasticity of gap junction communication at the level of the AP constitutes an additional mechanism affecting female reproduction.

  8. Urinary gonadotrophins: a useful non-invasive marker of activation of the hypothalamic pituitary-gonadal axis

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    McNeilly Jane D

    2012-05-01

    Full Text Available Abstract Background Non-invasive screening investigations are rarely used for assessing the activation and progression of the hypothalamic-pituitary gonadal axis through puberty. This study aimed to establish a normal range for urinary gonadotrophins in children progressing through puberty. Methods Urine samples were collected from 161 healthy school children (76 boys, 85 girls aged 4–19 yrs. Height and weight were converted to standard deviation score. Pubertal status, classified by Tanner staging, was determined by self-assessment. Urinary gonadotrophins were measured by chemiluminescent microparticle immunoassay. Results were grouped according to pubertal status (pre-pubertal or pubertal. Results Of the 161 children, 50 were pre-pubertal (28 boys; 22 girls and 111 were pubertal (48 boys; 63 girls. Overall, urinary gonadotrophins concentrations increased with pubertal maturation. All pre-pubertal children had a low urinary LH:Creatinine ratio. LH:Creatinine ratios were significantly higher in pubertal compared to pre-pubertal boys (pp = 0.006. However, LH:FSH ratios were a more consistent discriminant between pre-pubertal and pubertal states in both sexes (Boys 0.45 pubertal vs 0.1 pre-pubertal; girls 0.23 pubertal vs 0.06 pre-pubertal. Conclusion Urinary gonadotrophins analyses could be used as non-invasive integrated measurement of pubertal status which reflects clinical/physical status.

  9. Population pharmacokinetic/pharmacodynamic modelling of the hypothalamic-pituitary-gonadal axis

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    Tornøe, Christoffer Wenzel

    2005-01-01

    The present thesis deals with different aspects of population pharmacokinetic/ pharmacodynamic (PK/PD) modelling of the male hypothalamic-pituitary-go-nadal (HPG) axis. The thesis consists of a summary report and five scientific research papers. An overview of the main topics covered in the thesis...... is provided in the summary report including PK/PD modelling in drug development, the pathological, physiological, and pharmacological aspects of the male HPG axis, and a detailed description of the methodology behind non-linear mixed-effects modelling based on stochastic differential equations (SDEs......). The main objective of the work underlying this thesis was to develop mechanism-based population PK/PD models of the HPG axis. The HPG axis is a multivariate closed-loop control system consisting of regulatory hormonal feedback mechanisms. The number and complexity of the physiological mechanisms involved...

  10. Population pharmacokinetic/pharmacodynamic (PK/PD) modelling of the hypothalamic-pituitary-gonadal axis following treatment with GnRH analogues

    DEFF Research Database (Denmark)

    Tornøe, Christoffer Wenzel; Agersø, Henrik; Senderovitz, Thomas

    2007-01-01

    Aims To develop a population pharmacokinetic/pharmacodynamic (PK/PD) model of the hypothalamic-pituitary-gonadal (HPG) axis describing the changes in luteinizing hormone (LH) and testosterone concentrations following treatment with the gonadotropin-releasing hormone (GnRH) agonist triptorelin...... for the population PK/PD data analysis. A systematic population PK/PD model-building framework using stochastic differential equations was applied to the data to identify nonlinear dynamic dependencies and to deconvolve the functional feedback interactions of the HPG axis. Results In our final PK/PD model of the HPG...

  11. Alteration of the hypothalamic-pituitary-gonadal axis in estrogen- and androgen-treated adult male leopard frog, Rana pipiens

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    Jones Jeremy T

    2005-01-01

    Full Text Available Abstract Background Gonadal steroids, in particular 5 alpha-dihydrotestosterone (DHT and 17 beta-estradiol (E2, have been shown to feed back on the hypothalamic-pituitary-gonadal (HPG axis of the ranid frog. However, questions still remain on how DHT and E2 impact two of the less-studied components of the ranid HPG axis, the hypothalamus and the gonad, and if the feedback effects are consistently negative. Thus, the goal of the study was to examine the effects of DHT and E2 upon the HPG axis of the gonadally-intact, sexually mature male leopard frogs, Rana pipiens. Methods R. pipiens were implanted with silastic capsules containing either cholesterol (Ch, a control, DHT, or E2 for 10 or 30 days. At each time point, steroid-induced changes in hypothalamic GnRH and pituitary LH concentrations, circulating luteinizing hormone (LH, and testicular histology were examined. Results Frogs implanted with DHT or E2 for 10 days did not show significant alterations in the HPG axis. In contrast, frogs implanted with hormones for 30 days had significantly lower circulating LH (for both DHT and E2, decreased pituitary LH concentration (for E2 only, and disrupted spermatogenesis (for both DHT and E2. The disruption of spermatogenesis was qualitatively similar between DHT and E2, although the effects of E2 were consistently more potent. In both DHT and E2-treated animals, a marked loss of all pre-meiotic germ cells was observed, although the loss of secondary spermatogonia appeared to be the primary cause of disrupted spermatogenesis. Unexpectedly, the presence of post-meiotic germ cells was either unaffected or enhanced by DHT or E2 treatment. Conclusions Overall, these results showed that both DHT and E2 inhibited circulating LH and disrupted spermatogenesis progressively in a time-dependent manner, with the longer duration of treatment producing the more pronounced effects. Further, the feedback effects exerted by both steroid hormones upon the HPG axis were

  12. Effects of Microcystis on Hypothalamic-Pituitary-Gonadal-Liver Axis in Nile Tilapia (Oreochromis niloticus).

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    Chen, Jiazhang; Meng, Shunlong; Xu, Hai; Zhang, Zhen; Wu, Xiangyang

    2017-04-01

    In the present study, Nile tilapia (Oreochromis niloticus) were used to assess the endocrine disruption potential of Microcytis aeruginosa. Male Nile tilapia were exposed to lyophilized M. aeruginosa or purified microcystin-LR (8.3 μg/L) for 28 days. The levels of serum hormones (17β-estradiol and testosterone) and transcripts of selected genes in the hypothalamus-pituitary-gonadal-liver axis were analyzed. The results showed that serum hormones were significantly up-regulated, and transcripts of 13 genes (GHRH, PACAP, GH, GHR1, GHR2, IGF1, IGF2, CYP19a, CYP19b, 3β-HSD1, 20β-HSD, 17β-HSD1 and 17β-HSD8) were significantly altered after Microcytis exposure. These results indicate that fish reproduction can be altered in a Microcystis bloom-contaminated aquatic environment.

  13. Effects of aqueous extract from Asparagus officinalis L. roots on hypothalamic-pituitary-gonadal axis hormone levels and the number of ovarian follicles in adult rats

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    Hojatollah Karimi Jashni

    2016-02-01

    Full Text Available Background: Asparagus is a plant with high nutritional, pharmaceutical, and industrial values. Objective: The present study aimed to evaluate the effect of aqueous extract of asparagus roots on the hypothalamic-pituitary-gonadal axis hormones and oogenesis in female rats. Materials and Methods: In this experimental study, 40 adult female Wistar rats were divided into five groups, which consist 8 rats. Groups included control, sham and three experimental groups receiving different doses (100, 200, 400 mg/kg/bw of aqueous extract of asparagus roots. All dosages were administered orally for 28 days. Blood samples were taken from rats to evaluate serum levels of Gonadotropin releasing hormone (GnRH, follicular stimulating hormone (FSH, Luteinal hormone (LH, estrogen, and progesterone hormones. The ovaries were removed, weighted, sectioned, and studied by light microscope. Results: Dose-dependent aqueous extract of asparagus roots significantly increased serum levels of GnRH, FSH, LH, estrogen, and progestin hormones compared to control and sham groups. Increase in number of ovarian follicles and corpus luteum in groups treated with asparagus root extract was also observed (p<0.05. Conclusion: Asparagus roots extract stimulates secretion of hypothalamic- pituitary- gonadal axis hormones. This also positively affects oogenesis in female rats.

  14. Defining global gene expression changes of the hypothalamic-pituitary-gonadal axis in female sGnRH-antisense transgenic common carp (Cyprinus carpio.

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    Jing Xu

    Full Text Available BACKGROUND: The hypothalamic-pituitary-gonadal (HPG axis is critical in the development and regulation of reproduction in fish. The inhibition of neuropeptide gonadotropin-releasing hormone (GnRH expression may diminish or severely hamper gonadal development due to it being the key regulator of the axis, and then provide a model for the comprehensive study of the expression patterns of genes with respect to the fish reproductive system. METHODOLOGY/PRINCIPAL FINDINGS: In a previous study we injected 342 fertilized eggs from the common carp (Cyprinus carpio with a gene construct that expressed antisense sGnRH. Four years later, we found a total of 38 transgenic fish with abnormal or missing gonads. From this group we selected the 12 sterile females with abnormal ovaries in which we combined suppression subtractive hybridization (SSH and cDNA microarray analysis to define changes in gene expression of the HPG axis in the present study. As a result, nine, 28, and 212 genes were separately identified as being differentially expressed in hypothalamus, pituitary, and ovary, of which 87 genes were novel. The number of down- and up-regulated genes was five and four (hypothalamus, 16 and 12 (pituitary, 119 and 93 (ovary, respectively. Functional analyses showed that these genes involved in several biological processes, such as biosynthesis, organogenesis, metabolism pathways, immune systems, transport links, and apoptosis. Within these categories, significant genes for neuropeptides, gonadotropins, metabolic, oogenesis and inflammatory factors were identified. CONCLUSIONS/SIGNIFICANCE: This study indicated the progressive scaling-up effect of hypothalamic sGnRH antisense on the pituitary and ovary receptors of female carp and provided comprehensive data with respect to global changes in gene expression throughout the HPG signaling pathway, contributing towards improving our understanding of the molecular mechanisms and regulative pathways in the

  15. Effects of BPA and E2 on expression profiles of genes related to hypothalamic-pituitary-gonadal axis of half-smooth tongue sole Cynoglossus semilaevis

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    Li, Fengling; Li, Zhaoxin; Wang, Qingyin; Zhai, Yuxiu

    2013-05-01

    Endocrine disrupting chemicals (EDCs) are increasingly viewed as persistent pollutants, similar to natural hormones in function. This paper describes the expression profiles of 7 genes ( DMRT, VTG GnRHR FSHR CYP17A CYP19A, and CYP19B) involved in sex steroid synthesis and action as well as sexual development in adult male and female Cynoglossus semilaevis, after exposure to different concentrations of Bisphenol A (BPA) and 17β-estradiol (E2). Both BPA (1, 10, 50, 125, and 250 mg/kg) and E2 (0.5, 5, and 10 mg/kg) induced changes in target gene expression, although the estrogenic effects of E2 as a model estrogen were stronger. Among the 7 genes, VTG CYP17A and CYP19 responded strongly to BPA or E2 exposure and can thus serve as reference biomarkers for estrogenic EDCs exposure in marine teleosts. These data will provide a window to establish a hypothalamic-pituitary-gonadal model in C. semilaevis to better understand the effect pathways of EDCs.

  16. Standardized quassinoid-rich Eurycoma longifolia extract improved spermatogenesis and fertility in male rats via the hypothalamic-pituitary-gonadal axis.

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    Low, Bin-Seng; Das, Prashanta Kumar; Chan, Kit-Lam

    2013-02-13

    control (P<0.05). The estimated spermatozoa production rate and the number of Leydig cells were also elevated (P<0.001). The fertility index, fecundity index and the pup litter size delivered from the females after mating with the males treated with F2 were increased. The plasma testosterone level of the animals given 25mg/kg of F2 orally was significantly different at day-26 (p<0.05) and day-52 (P<0.01) from those of control but was not different at day-104. The testicular testosterone also peaked in the animals treated with 25mg/kg F2 and was higher than that in the plasma. The plasma LH and FSH levels of the rats treated with 25mg/kg of F2 were higher than those of the control (P<0.001). In contrast, the plasma estrogen level was significantly lower than that of the untreated control. Amongst the isolated quassinoids of F2, eurycomanone and 13α(21)-dihydroeurycomaone significantly increased the testosterone level from the Leydig cells of the testicular interstitial cells cultured in vitro (P<0.05). The standardised extract F2 of E. longifolia and its major quassinoids especially eurycomanone improved the rat spermatogenesis by affecting the hypothalamic-pituitary-gonadal axis and the potential efficacy may be worthy of further investigation. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  17. Sex-Specific Effects of Chronic Administration of Relaxin-3 on Food Intake, Body Weight and the Hypothalamic-Pituitary-Gonadal Axis in Rats.

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    Calvez, J; de Ávila, C; Guèvremont, G; Timofeeva, E

    2016-12-01

    The present study examined the effects of chronic central administration of relaxin-3 (RLN3) on food intake, body weight and fat mass in intact and sterilised male and female rats, as well as on hypothalamic-pituitary-gonadal (HPG) axis activity in intact male and female rats that received i.c.v. infusions of RLN3 (400 pmol/day) or vehicle during a 14-day period. The intact RLN3-injected rats displayed a higher body weight than the vehicle-treated groups, and this increase was statistically significantly stronger in female rats compared to male rats. In addition, feed efficiency and gonadal white adipose tissue weight were higher in female RLN3-injected rats. Chronic i.c.v. administration of RLN3 activated the HPG axis in intact male rats, whereas inhibition of the HPG axis was observed in intact female rats. RLN3 significantly increased the plasma levels of luteinising hormone and follicular-stimulating hormone in male rats but not in female rats. Conversely, hypothalamic expression of gonadotrophin-releasing hormone mRNA was decreased by RLN3 in female rats but not in male rats. In addition, the plasma levels of oestradiol were significantly decreased by RLN3 administration in female rats. Consequently, intact RLN3-injected female rats failed to display phasic inhibition of eating during oestrus. Sex-specific effects of RLN3 on food intake and body weight were also observed in ovariectomised female and orchidectomised male rats, suggesting that the sex-specific effects of RLN3 on energy metabolism are independent on the differential effects of RLN3 on HPG axis activity in male and female rats. © 2016 British Society for Neuroendocrinology.

  18. Hypothalamic-pituitary-gonadal axis hormones and cortisol in both menstrual phases of women with chronic fatigue syndrome and effect of depressive mood on these hormones

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    Nas Kemal

    2004-12-01

    Full Text Available Abstract Background Chronic fatigue syndrome (CFS is a disease which defined as medically unexplained, disabling fatigue of 6 months or more duration and often accompanied by several of a long list of physical complaints. We aimed to investigate abnormalities of hypothalamic-pituitary-gonadal (HPG axis hormones and cortisol concentrations in premenopausal women with CFS and find out effects of depression rate on these hormones. Methods We examined follicle stimulating hormone (FSH, luteinizing hormone (LH, estradiol, progesterone and cortisol concentrations in 43 premenopausal women (mean age: 32.86 ± 7.11 with CFS and compared matched 35 healthy controls (mean age: 31.14 ± 6.19. Patients were divided according to menstrual cycle phases (follicular and luteal and compared with matched phase controls. Depression rate was assessed by Beck Depression Inventory (BDI, and patients with high BDI scores were compared to patients with low BDI scores. Results There were no significant differences in FSH, LH, estradiol and progesterone levels in both of menstrual phases of patients versus controls. Cortisol levels were significantly lower in patients compared to controls. There were no significant differences in all hormone levels in patients with high depression scores versus patients with low depression scores. Conclusion In spite of high depression rate, low cortisol concentration and normal HPG axis hormones of both menstrual phases are detected in premenopausal women with CFS. There is no differentiation between patients with high and low depression rate in all hormone levels. Depression condition of CFS may be different from classical depression and evaluation of HPG and HPA axis should be performed for understanding of pathophysiology of CFS and planning of treatment.

  19. A computational model of the hypothalamic - pituitary - gonadal axis in female fathead minnows (Pimephales promelas exposed to 17α-ethynylestradiol and 17β-trenbolone

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    Lazorchak James M

    2011-05-01

    Full Text Available Abstract Background Endocrine disrupting chemicals (e.g., estrogens, androgens and their mimics are known to affect reproduction in fish. 17α-ethynylestradiol is a synthetic estrogen used in birth control pills. 17β-trenbolone is a relatively stable metabolite of trenbolone acetate, a synthetic androgen used as a growth promoter in livestock. Both 17α-ethynylestradiol and 17β-trenbolone have been found in the aquatic environment and affect fish reproduction. In this study, we developed a physiologically-based computational model for female fathead minnows (FHM, Pimephales promelas, a small fish species used in ecotoxicology, to simulate how estrogens (i.e., 17α-ethynylestradiol or androgens (i.e., 17β-trenbolone affect reproductive endpoints such as plasma concentrations of steroid hormones (e.g., 17β-estradiol and testosterone and vitellogenin (a precursor to egg yolk proteins. Results Using Markov Chain Monte Carlo simulations, the model was calibrated with data from unexposed, 17α-ethynylestradiol-exposed, and 17β-trenbolone-exposed FHMs. Four Markov chains were simulated, and the chains for each calibrated model parameter (26 in total converged within 20,000 iterations. With the converged parameter values, we evaluated the model's predictive ability by simulating a variety of independent experimental data. The model predictions agreed with the experimental data well. Conclusions The physiologically-based computational model represents the hypothalamic-pituitary-gonadal axis in adult female FHM robustly. The model is useful to estimate how estrogens (e.g., 17α-ethynylestradiol or androgens (e.g., 17β-trenbolone affect plasma concentrations of 17β-estradiol, testosterone and vitellogenin, which are important determinants of fecundity in fish.

  20. Acute fasting-induced repression of the hypothalamic-pituitary-gonadal axis is reversed by RF-9 administration in the adult male macaque.

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    Batool, A; Naz, R; Wazir, M; Azam, A; Ullah, R; Wahab, F; Shahab, M

    2014-12-01

    Recently, hypothalamic RFRP-3 (a mammalian ortholog of avian GnIH) signaling has been proposed as an important negative modulator of the reproductive axis. The current study examined whether repression of reproductive hormonal expression during short-term fasting conditions in higher-order primate is influenced by altered RFRP-3 signaling. Eight intact postpubertal male macaques (Macaca mulatta) were administered a single intravenous bolus of RF-9 (n = 4), a potent and putative RFRP-3 receptor antagonist, or vehicle (n = 4) following a 48-h fasting condition. Intermittent blood samples were collected every 30 min during the 4-h post-bolus period, and blood glucose, plasma cortisol, and testosterone concentrations were measured. Relative to fed conditions, fasting reduced glucose and testosterone levels (p < 0.005) and increased cortisol levels (p < 0.05). Relative to baseline, mean testosterone levels were elevated 150 min after RF-9 (p < 0.05) but not vehicle administration. In addition, elevated mean plasma testosterone levels following RF-9 administration were equivalent to levels observed in normal fed monkeys. These results suggest an important role for RFRP-3 signaling in conveying metabolic state information to the reproductive axis in higher primates. © Georg Thieme Verlag KG Stuttgart · New York.

  1. Hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal axes: sex differences in regulation of stress responsivity.

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    Oyola, Mario G; Handa, Robert J

    2017-09-01

    Gonadal hormones play a key role in the establishment, activation, and regulation of the hypothalamic-pituitary-adrenal (HPA) axis. By influencing the response and sensitivity to releasing factors, neurotransmitters, and hormones, gonadal steroids help orchestrate the gain of the HPA axis to fine-tune the levels of stress hormones in the general circulation. From early life to adulthood, gonadal steroids can differentially affect the HPA axis, resulting in sex differences in the responsivity of this axis. The HPA axis influences many physiological functions making an organism's response to changes in the environment appropriate for its reproductive status. Although the acute HPA response to stressors is a beneficial response, constant activation of this circuitry by chronic or traumatic stressful episodes may lead to a dysregulation of the HPA axis and cause pathology. Compared to males, female mice and rats show a more robust HPA axis response, as a result of circulating estradiol levels which elevate stress hormone levels during non-threatening situations, and during and after stressors. Fluctuating levels of gonadal steroids in females across the estrous cycle are a major factor contributing to sex differences in the robustness of HPA activity in females compared to males. Moreover, gonadal steroids may also contribute to epigenetic and organizational influences on the HPA axis even before puberty. Correspondingly, crosstalk between the hypothalamic-pituitary-gonadal (HPG) and HPA axes could lead to abnormalities of stress responses. In humans, a dysregulated stress response is one of the most common symptoms seen across many neuropsychiatric disorders, and as a result, such interactions may exacerbate peripheral pathologies. In this review, we discuss the HPA and HPG axes and review how gonadal steroids interact with the HPA axis to regulate the stress circuitry during all stages in life.

  2. A computational model linking oocyte growth and spawning to the hypothalamic-pituitary-gonadal axis in fathead minnow (Pimephales promelas)

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    Reproduction is vital to the survival of all living organisms, and reproductive toxicity is an important outcome in determining the ecological risks of chemicals in the environment. To evaluate reproductive toxicity, fathead minnow fecundity, as measured by the average number of...

  3. A Computational Model of the Hypothalamic-pituitary-gonadal Axis in Male Fathead Minnows Exposed to 17 | *alpha* | -ethinylestradiol and 17 | *beta* | -estradiol

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    Estrogenic chemicals in the aquatic environment have been shown to cause a variety of reproductive anomalies in fish including full sex reversal, intersex, and altered population sex ratios. Two estrogens found in the aquatic environment, 17-ethinylestradiol and 17â-estradiol, h...

  4. Orexin receptor expression in the hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal axes of free-living European beavers (Castor fiber L.) in different periods of the reproductive cycle.

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    Czerwinska, Joanna; Chojnowska, Katarzyna; Kaminski, Tadeusz; Bogacka, Iwona; Smolinska, Nina; Kaminska, Barbara

    2017-01-01

    Orexins are hypothalamic neuropeptides acting via two G protein-coupled receptors in mammals: orexin receptor 1 (OX1R) and orexin receptor 2 (OX2R). In European beavers, which are seasonally breeding animals, the presence and functions of orexins and their receptors remain unknown. Our study aimed to determine the expression of OXR mRNAs and the localization of OXR proteins in hypothalamic-pituitary-adrenal/gonadal (HPA/HPG) axes in free-living beavers. The expression of OXR genes (OX1R, OX2R) and proteins was found in all analysed tissues during three periods of beavers' reproductive cycle (April, July, November). The expression of OXR mRNAs in the beaver HPA axis varied seasonally (P<0.05). The levels of OX1R mRNA also differed between the sexes (P<0.05). In the mediobasal hypothalamus, OX1R transcript content increased in pregnant females in April (P<0.05) and OX2R expression increased in males in July (P<0.05). In the pituitary and adrenals, OX1R mRNA levels were relatively constant in females and peaked in July in males (P<0.05), whereas the OX2R was most highly expressed in males in November and in females in April (P<0.05). In gonads, OX1R expression did not fluctuate between seasons or sexes, but transcript levels were elevated in the testes in November and in the ovaries in July (P<0.05). In turn, OX2R mRNA levels varied between the sexes (P<0.05) and were higher in females (July and November) than in males (P<0.05). The circannual variations in OXR mRNA levels in HPA and HPG axes suggest that the expression of these receptors is associated with sex-specific changes in beavers' reproductive activity and their environmental adaptations. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Adult exposure to bisphenol A (BPA) in Wistar rats reduces sperm quality with disruption of the hypothalamic-pituitary-testicular axis.

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    Wisniewski, Patricia; Romano, Renata M; Kizys, Marina M L; Oliveira, Kelen C; Kasamatsu, Teresa; Giannocco, Gisele; Chiamolera, Maria I; Dias-da-Silva, Magnus R; Romano, Marco A

    2015-03-02

    Reproductive physiology involves complex biological processes that can be disrupted by exposure to environmental contaminants. The effects of bisphenol A (BPA) on spermatogenesis and sperm quality is still unclear. The objective of this study was to investigate the reproductive toxicity of BPA at dosages considered to be safe (5 or 25mg BPA/kg/day). We assessed multiple sperm parameters, the relative expression of genes involved in the central regulation of the hypothalamic-pituitary-testicular axis, and the serum concentrations of testosterone, estradiol, LH and FSH. BPA exposure reduced sperm production, reserves and transit time. Significant damage to the acrosomes and the plasma membrane with reduced mitochondrial activity and increased levels of defective spermatozoa may have compromised sperm function and caused faster movement through the epididymis. BPA exposure reduced the serum concentrations of testosterone, LH and FSH and increased the concentration of estradiol. The relative gene expression revealed an increase in gonadotropin releasing hormone receptor (Gnrhr), luteinizing hormone beta (Lhb), follicle stimulating hormone beta (Fshb), estrogen receptor beta (Esr2) and androgen receptor (Ar) transcripts in the pituitary and a reduction in estrogen receptor alpha (Esr1) transcripts in the hypothalamus. In this study, we demonstrated for the first time that adult male exposure to BPA caused a reduction in sperm production and specific functional parameters. The corresponding pattern of gene expression is indicative of an attempt by the pituitary to reestablish normal levels of LH, FSH and testosterone serum concentrations. In conclusion, these data suggest that at dosages previously considered nontoxic to reproductive function, BPA compromises the spermatozoa and disrupts the hypothalamic-pituitary-gonadal axis, causing a state of hypogonadotropic hypogonadism. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  6. Urine gonadotropin and testosterone levels in male very-low-birthweight infants

    NARCIS (Netherlands)

    de Jong, M.; Rotteveel, J.; Heijboer, A. C.; Cranendonk, A.; Twisk, J. W. R.; van Weissenbruch, M. M.

    2012-01-01

    The postnatal activation of the hypothalamic-pituitary-gonadal axis is more exaggerated in preterm than in full-term-born infants, and may be important for reproductive function. Our objective was to investigate this activation of the hypothalamic-pituitary-gonadal axis in male very-low-birthweight

  7. A review of the incidence and survival of childhood and adolescent ...

    African Journals Online (AJOL)

    Cancer is not uncommon in children. The reproductive system is an important site for late effects of cancer treatment, and normal pubertal development depends on an undamaged hypothalamic-pituitary-gonadal axis. Fertility compromise can occur due to chemotherapy, radiotherapy to the hypothalamic-pituitary-gonadal ...

  8. Maternal programming of sexual behavior and hypothalamic-pituitary-gonadal function in the female rat.

    Directory of Open Access Journals (Sweden)

    Nicole Cameron

    Full Text Available Variations in parental care predict the age of puberty, sexual activity in adolescence and the age at first pregnancy in humans. These findings parallel descriptions of maternal effects on phenotypic variation in reproductive function in other species. Despite the prevalence of such reports, little is known about potential biological mechanisms and this especially true for effects on female reproductive development. We examined the hypothesis that parental care might alter hypothalamic-pituitary-ovarian function and thus reproductive function in the female offspring of rat mothers that vary pup licking/grooming (LG over the first week postpartum. As adults, the female offspring of Low LG mothers showed 1 increased sexual receptivity; 2 increased plasma levels of luteinizing hormone (LH and progesterone at proestrus; 3 an increased positive-feedback effect of estradiol on both plasma LH levels and gonadotropin releasing-hormone (GnRH expression in the medial preoptic region; and 4 increased estrogen receptor alpha (ERalpha expression in the anterioventral paraventricular nucleus, a system that regulates GnRH. The results of a cross-fostering study provide evidence for a direct effect of postnatal maternal care as well as a possible prenatal influence. Indeed, we found evidence for increased fetal testosterone levels at embryonic day 20 in the female fetuses of High compared to Low LG mothers. Finally, the female offspring of Low LG mothers showed accelerated puberty compared to those of High LG mothers. These data suggest maternal effects in the rat on the development of neuroendocrine systems that regulate female sexual behaviour. Together with studies revealing a maternal effect on the maternal behavior of the female offspring, these findings suggest that maternal care can program alternative reproductive phenotypes in the rat through regionally-specific effects on ERalpha expression.

  9. Hypothalamic-pituitary-gonadal function in men with liver cirrhosis before and after liver transplantation

    Directory of Open Access Journals (Sweden)

    Bruno T. Zacharias

    2014-12-01

    Full Text Available Objective: To evaluate the influence of end-stage liver disease and orthotopic liver transplantation in the pituitary function and hormone metabolism before and after liver transplantation.Methods: In a prospective study, serum levels of follicle stimulating hormone (FSH, luteinizing hormone (LH, estradiol (E2 and prolactin (PRL of 30 male patients with cirrhosis were determined two to four hours before and six months after liver transplantation. The results were compared according to the Model for End-stage Liver Disease (MELD.Results: male patients with liver cirrhosis have hypogonadism. FSH was normal, but inappropriately low due to androgen failure; E2 and PRL, on their turn, were high. After liver transplantation, FSH and LH levels increased (p 18. The severity of cirrhosis had no influence on FSH, PRL and LH.

  10. Hypothalamic-pituitary-gonadal function in men with liver cirrhosis before and after liver transplantation.

    Science.gov (United States)

    Zacharias, Bruno T; Coelho, Julio C U; Parolin, Mônica B; Matias, Jorge E F; Freitas, Alexandre C T de; Godoy, José Luiz de

    2014-01-01

    To evaluate the influence of end-stage liver disease and orthotopic liver transplantation in the pituitary function and hormone metabolism before and after liver transplantation. In a prospective study, serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2) and prolactin (PRL) of 30 male patients with cirrhosis were determined two to four hours before and six months after liver transplantation. The results were compared according to the Model for End-stage Liver Disease (MELD). male patients with liver cirrhosis have hypogonadism. FSH was normal, but inappropriately low due to androgen failure; E2 and PRL, on their turn, were high. After liver transplantation, FSH and LH levels increased (p 18. The severity of cirrhosis had no influence on FSH, PRL and LH.

  11. Hypothalamic-pituitary-gonadal function in relation to liver function in men with alcoholic cirrhosis

    DEFF Research Database (Denmark)

    Gluud, C; Bahnsen, M; Bennett, Patrick

    1983-01-01

    Serum concentrations of oestrone, oestradiol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and sex hormone-binding globulin (SHBG) were significantly (P less than 0.01) raised in men with alcoholic liver cirrhosis (no. = 42) compared with age-matched controls (no. = 20). No signi......Serum concentrations of oestrone, oestradiol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and sex hormone-binding globulin (SHBG) were significantly (P less than 0.01) raised in men with alcoholic liver cirrhosis (no. = 42) compared with age-matched controls (no. = 20...... affected liver function (no. = 18) had significantly (P less than 0.05) raised serum concentrations of testosterone, FSH, and LH when compared with both controls and patients with severely affected liver function (no. = 13). Serum concentrations of testosterone, FSH, and LH in the latter group showed...... groups of patients. Dexamethasone suppression did not change the concentration of testosterone significantly, but oestrone and oestradiol concentrations decreased significantly (P less than 0.01) in controls and patients. In patients, but not in controls, a significant (P less than 0.01) increase in FSH...

  12. Effects of the insecticide fipronil on reproductive endocrinology in the fathead minnow

    Science.gov (United States)

    Gamma aminobutyric acid (GABA) and GABA receptors play an important role in neuroendocrine regulation in fish. Disruption of the GABAergic system by environmental contaminants could interfere with normal regulation of the hypothalamic pituitary gonadal (HPG) axis, leading to imp...

  13. Kisspeptin stimulates growth hormone release by utilizing Neuropeptide Y pathways and is dependent on the presence of ghrelin

    Science.gov (United States)

    Although kisspeptin is the primary stimulator of gonadotropin releasing hormone secretion and therefore the hypothalamic-pituitary gonadal axis, new findings suggest kisspeptin can also regulate additional neuroendocrine processes including release of growth hormone (GH). Central delivery of kisspep...

  14. High normal testosterone levels in infants with non-mosaic Klinefelter's syndrome

    DEFF Research Database (Denmark)

    Aksglaede, Lise; Petersen, Jørgen H; Main, Katharina M

    2007-01-01

    Klinefelter's syndrome (KS) is associated with hypergonadotrophic hypogonadism in adulthood. However, limited information exists about the age at which hypogonadism occurs. The hypothalamic-pituitary-gonadal (HPG) axis is transiently activated during the first months of life, offering...

  15. Assessment of wastewater treatment plant effluent effects on fish reproduction

    Science.gov (United States)

    Wastewater treatment plant (WWTP) effluents are known contributors of chemical mixtures into the environment. Of particular concern are endocrine-disrupting compounds that can affect hypothalamic-pituitary-gonadal axis function in exposed organisms. The present study examined t...

  16. Pathway-based approaches for assessment of real-time exposure to an estrogenic wastewater treatment plant effluent on fathead minnow reproduction

    Science.gov (United States)

    Wastewater treatment plant (WWTP) effluents are known contributors of chemical mixtures into the environment. Of particular concern are endocrine-disrupting compounds, such as estrogens, that can affect hypothalamic-pituitary-gonadal axis function in exposed organisms. The presen...

  17. High normal testosterone levels in infants with non-mosaic Klinefelter's syndrome

    DEFF Research Database (Denmark)

    Aksglaede, Lise; Petersen, Jørgen H; Main, Katharina M

    2007-01-01

    Klinefelter's syndrome (KS) is associated with hypergonadotrophic hypogonadism in adulthood. However, limited information exists about the age at which hypogonadism occurs. The hypothalamic-pituitary-gonadal (HPG) axis is transiently activated during the first months of life, offering the opportu...

  18. Simultaneous analysis of thirteen endogenous steroid hormones by liquid chromatography tandem mass spectrometry with atmospheric pressure photoionization

    Science.gov (United States)

    Exposure to endocrine active chemicals can lead to perturbations of the hypothalamic-pituitary-gonadal (HPG) axis, ultimately leading to adverse reproductive effects. To evaluate potential reproductive effects, many aquatic toxicity assessments still rely on radioimmunoassay (RIA...

  19. Detection of endocrine disrupting chemicals and evidence of their effects on the HPG axis of the European anchovy Engraulis encrasicolus.

    Science.gov (United States)

    Miccoli, Andrea; Maradonna, Francesca; De Felice, Andrea; Caputo Barucchi, Vincenzo; Estonba, Andone; Genangeli, Michele; Vittori, Sauro; Leonori, Iole; Carnevali, Oliana

    2017-06-01

    Natural/synthetic Endocrine Disrupting Chemicals (EDCs) may display estrogenic activity and a lower potency than 17β-estradiol. Nonetheless, their concentrations and additive effects can affect the endocrine system and reproductive processes related to the Hypothalamic-Pituitary-Gonadal (HPG) axis. Because of their persistence in both the environment and biological systems, they ultimately target multi-level predators, including humans. We detected presence and effects of xenobiotics on wild anchovy Engraulis encrasicolus in the Western Adriatic Sea. Twenty-one PCBs and five organochlorines were detected on the order of ng g -1 ; vitellogenin, vitellogenin receptor and genes encoding for the zona radiata proteins were evaluated in gonad and/or liver and found transcribed in male specimens; in addition, intersex was histologically identified in the 13% of testis. Our results have developed the understanding of the European anchovy's reproductive toxicological risk and our approach could assist the comprehension of the complex dynamics of commercially relevant Teleost species. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Gonadotropin inhibitory hormone and RF9 stimulate hypothalamic-pituitary-adrenal axis in adult male rhesus monkeys.

    Science.gov (United States)

    Ullah, Rahim; Batool, Aalia; Wazir, Madiha; Naz, Rabia; Rahman, Tanzil Ur; Wahab, Fazal; Shahab, Muhammad; Fu, Junfen

    2017-12-01

    Stress activates gonadotropin inhibitory hormone (GnIH), hypothalamic-pituitary-adrenal axis (HPA-axis) and represses hypothalamic-pituitary-gonadal axis (HPG-axis) but RF9 administration relieves stress-induced repression of the HPG-axis. Importantly, it was not known whether GnIH signaling and RF9 synthetic peptide modulate the HPA axis. To assess this, mammalian orthologs of GnIH (RFRP-1 and RFRP-3) and RF9 were administered to intact adult male rhesus monkeys. RFRP-1 (125μg/animal), RFRP-3 (250μg/animal) and RF9 (0.1mg/kg BW) were intravenously (iv) injected into normal fed (n=4) monkeys. Additionally, a single bolus iv injection of RF9 (0.1mg/kg BW) was also administered to 48h fasted monkeys (n=4) to check the effects of RF9 signaling on an activated HPA-axis. Serial blood samples were collected, centrifuged and the obtained plasma was used for the analysis of cortisol by specific enzyme immunoassay. RFRP-1 treatment significantly increased cortisol levels while RFRP-3 increased the plasma cortisol, but the effect was non-significant. RF9 treatment significantly increased cortisol levels in normal fed animals. In contrast, RF9 injection did not significantly alter circulating cortisol in fasted monkeys. In conclusion, our results suggest stimulatory action of RFRPs and RF9 on the HPA axis in the adult male monkeys. However, the mechanism and site of action of RFRP-1 and RF9 along the HPA-axis is still unknown. Therefore, further studies are needed to decipher the mechanism and site of action of RFRPs and RF9 on the HPA axis in primates. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Food restriction negatively affects multiple levels of the reproductive axis in male house finches, Haemorhous mexicanus.

    Science.gov (United States)

    Valle, Shelley; Carpentier, Elodie; Vu, Bethany; Tsutsui, Kazuyoshi; Deviche, Pierre

    2015-09-01

    Nutrition influences reproductive functions across vertebrates, but the effects of food availability on the functioning of the hypothalamic-pituitary-gonadal (HPG) axis in wild birds and the mechanisms mediating these effects remain unclear. We investigated the influence of chronic food restriction on the HPG axis of photostimulated house finches, Haemorhous mexicanus. Food-restricted birds had underdeveloped testes with smaller seminiferous tubules than ad libitum-fed birds. Baseline plasma testosterone increased in response to photostimulation in ad libitum-fed but not in food-restricted birds. Food availability did not, however, affect the plasma testosterone increase resulting from a gonadotropin-releasing hormone-I (GnRH) or a luteinizing hormone (LH) challenge. The number of hypothalamic GnRH immunoreactive (ir) but not proGnRH-ir perikarya was higher in food-restricted than in ad libitum-fed finches, suggesting inhibited secretion of GnRH. Hypothalamic gonadotropin-inhibitory hormone (GnIH)-ir and neuropeptide Y (NPY)-ir were not affected by food availability. Plasma corticosterone (CORT) was also not affected by food availability, indicating that the observed HPG axis inhibition did not result from increased activity of the hypothalamic-pituitary-adrenal (HPA) axis. This study is among the first to examine multilevel functional changes in the HPG axis in response to food restriction in a wild bird. The results indicate that food availability affects both hypothalamic and gonadal function, but further investigations are needed to clarify the mechanisms by which nutritional signals mediate these effects. © 2015. Published by The Company of Biologists Ltd.

  2. Suicide attempt by jumping: a study of gonadal axis hormones in male suicide attempters versus men who fell by accident.

    Science.gov (United States)

    Markianos, Manolis; Tripodianakis, John; Istikoglou, Christos; Rouvali, Olga; Christopoulos, Markos; Papageorgopoulos, Pavlos; Seretis, Andreas

    2009-11-30

    Low plasma total testosterone (T) levels may influence the sense of well-being and produce depressive symptomatology, increasing the risk of suicide. In a previous study, we reported reduced serum T levels in male psychiatric patients after a suicide attempt. The reduction was more pronounced in subjects who used violent attempt methods, and we discussed the possible influence of stress of hospitalization, serious medical condition and treatment. In order to minimize the influence of such factors, we compared in this study the levels of plasma sex hormones of 15 psychiatric patients (10 suffering from schizophrenia and 5 from depression) who had attempted suicide by jumping with those of a group of 18 male subjects who were hospitalized after accidentally falling from a high height. Compared with a healthy control group of 40 males, both accident and attempt groups had lower T levels. The attempt group showed a trend toward lower T levels compared with levels in the accident group. In the accident group, luteinizing hormone (LH) levels were elevated compared with levels in healthy controls, indicating a normal function of the hypothalamic-pituitary-gonadal (HPG) axis. This was not the case for the attempt group, where low T levels were not accompanied by increases in LH. Cortisol and prolactin were similarly elevated in both patient groups, but were not related to the low T levels. The results indicate that male psychiatric patients who attempt suicide by violent methods may have low total plasma T levels, possibly due to a dysfunction of the HPG axis at the hypothalamic-pituitary level. Monitoring HPG axis function in future studies could prove to be a predictor of suicide at least for male psychiatric attempters, and could lead to preventive strategies.

  3. Combined treatment with melatonin and insulin improves glycemic control, white adipose tissue metabolism and reproductive axis of diabetic male rats.

    Science.gov (United States)

    Oliveira, Ariclecio Cunha de; Andreotti, Sandra; Sertie, Rogério António Laurato; Campana, Amanda Baron; de Proença, André Ricardo Gomes; Vasconcelos, Renata Prado; Oliveira, Keciany Alves de; Coelho-de-Souza, Andrelina Noronha; Donato-Junior, José; Lima, Fábio Bessa

    2018-04-15

    Melatonin treatment has been reported to be capable of ameliorating metabolic diabetes-related abnormalities but also to cause hypogonadism in rats. We investigated whether the combined treatment with melatonin and insulin can improve insulin resistance and other metabolic disorders in rats with streptozotocin-induced diabetes during neonatal period and the repercussion of this treatment on the hypothalamic-pituitary-gonadal axis. At the fourth week of age, diabetic animals started an 8-wk treatment with only melatonin (0.2 mg/kg body weight) added to drinking water at night or associated with insulin (NHP, 1.5 U/100 g/day) or only insulin. Animals were then euthanized, and the subcutaneous (SC), epididymal (EP), and retroperitoneal (RP) fat pads were excised, weighed and processed for adipocyte isolation for morphometric analysis as well as for measuring glucose uptake, oxidation, and incorporation of glucose into lipids. Hypothalamus was collected for gene expression and blood samples were collected for biochemical assays. The treatment with melatonin plus insulin (MI) was capable of maintaining glycemic control. In epididymal (EP) and subcutaneous (SC) adipocytes, the melatonin plus insulin (MI) treatment group recovered the insulin responsiveness. In the hypothalamus, melatonin treatment alone promoted a significant reduction in kisspeptin-1, neurokinin B and androgen receptor mRNA levels, in relation to control group. Combined treatment with melatonin and insulin promoted a better glycemic control, improving insulin sensitivity in white adipose tissue (WAT). Indeed, melatonin treatment reduced hypothalamic genes related to reproductive function. Copyright © 2017. Published by Elsevier Inc.

  4. Effects of triclosan on hormones and reproductive axis in female Yellow River carp (Cyprinus carpio): Potential mechanisms underlying estrogen effect.

    Science.gov (United States)

    Wang, Fan; Guo, Xiangmeng; Chen, Wanguang; Sun, Yaowen; Fan, Chaojie

    2017-12-01

    Triclosan (TCS), a member of the class of compounds called pharmaceutical and personal care products (PPCPs), is a broad antibacterial and antifungal agent found in a lot of consumer products. However, TCS hormone effect mechanism in teleost female fish is not clear. Female Yellow River carp (Cyprinus carpio) were exposed to 1/20, 1/10 and 1/5 LC 50 TCS (96h LC 50 of TCS to carp) under semi-static conditions for 42days. Vitellogenin (Vtg), 17β-estradiol (E 2 ), testosterone(T), estrogen receptor (Er), gonadotropin (GtH), and gonadotropin-releasing hormone (GnRH) levels were measured by enzyme-linked immunosorbent assay (ELISA). Meanwhile, we also examined the mRNA expressions of aromatase, GtHs-β, GnRH, and Er by quantitative real-time PCR (qRT-PCR). The results indicated that 1/5 LC 50 TCS induced Vtg in hepatopancreas of female carps by interference with the hypothalamic-pituitary-gonadal (HPG) axis at multiple potential loci through three mechanisms: (a) TCS exposure enhanced the mRNA expression of hypothalamus and gonadal aromatase which converts androgens into estrogens, subsequently increasing serum concentrations of E 2 to induce Vtg in hepatopancreas; (b) TCS treatment increased GnRH and GtH-β mRNA expression and secretion, causing the disturbance of reproductive endocrine and the increase of E 2 to induce Vtg in hepatopancreas; (c) TCS exposure enhanced synthesis and secretion of Er, then it bound to Er to active Vtg synthesis. These mechanisms showed that TCS may induce Vtg production in female Yellow River carp by Er-mediated and non-Er-mediated pathways. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Hypothalamic-pituitary-ovarian axis perturbation in the basis of bisphenol A (BPA) reproductive toxicity in female zebrafish (Danio rerio).

    Science.gov (United States)

    Molina, Ana; Abril, Nieves; Morales-Prieto, Noelia; Monterde, José; Ayala, Nahúm; Lora, Antonio; Moyano, Rosario

    2018-03-14

    Thousands of safety-related studies have been published on bisphenol A (BPA), an ubiquitous environmental pollutant with estrogenic activity and many other potential biological effects. In recent years, BPA exposure has been shown to cause anovulation and infertility through irreversible alteration of the hypothalamic-pituitary-gonadal axis in several organisms, including fish and mammals. Recently, the European Chemical Agency classified BPA as a "substance of very high concern" because of its endocrine-disrupting properties, which have serious effects on human health. Given the risk of exposure to BPA as a pollutant in the environment, food, and drinking water, the objective of our study was to assess the effects of this compound on the adeno-hypophysis by means of a histopathological and morphometric study of the gonadotroph cells. In addition, using quantitative real-time PCR (qRT-PCR) assays, we analyzed the changes in the expression of Cyp19b (an aromatase gene). Zebrafish were randomly distributed into five groups: a control group and 4 treated groups which were exposed to different BPA concentrations (1, 10, 100 and 1000 µg/L). The effects of the different doses on Cyp19b mRNA molecules followed a non-monotonic curve, with the 1 and 1000 µg/L doses causing dramatic decreases in the number of Cyp19b transcripts while the doses of 10 and 100 µg/L caused important increases. The consequences might be deregulation of gonadotropic hormones causing degeneration of gonadotropic cells, as observed in BPA treated animals. This is the first study in which the gonadotroph cells have been evaluated using histomorphological endpoints after BPA exposure in zebrafish. Copyright © 2018 Elsevier Inc. All rights reserved.

  6. Hypopituitarism in the elderly: a narrative review on clinical management of hypothalamic-pituitary-gonadal, hypothalamic-pituitary-thyroid and hypothalamic-pituitary-adrenal axes dysfunction.

    Science.gov (United States)

    Curtò, L; Trimarchi, F

    2016-10-01

    Hypopituitarism is an uncommon and under-investigated endocrine disorder in old age since signs and symptoms are unspecific and, at least in part, can be attributed to the physiological effects of aging and related co-morbidities. Clinical presentation is often insidious being characterized by non-specific manifestations, such as weight gain, fatigue, low muscle strength, bradipsychism, hypotension or intolerance to cold. In these circumstances, hypopituitarism is a rarely life-threatening condition, but evolution may be more dramatic as a result of pituitary apoplexy, or when a serious condition of adrenal insufficiency suddenly occurs. Clinical presentation depends on the effects that each pituitary deficit can cause, and on their mutual relationship, but also, inevitably, it depends on the severity and duration of the deficit itself, as well as on the general condition of the patient. Indeed, indications and methods of hormone replacement therapy must include the need to normalize the endocrine profile without contributing to the worsening of intercurrent diseases, such as those of glucose and bone metabolism, and the cardiovascular system, or to the increasing cancer risk. Hormonal requirements of elderly patients are reduced compared to young adults, but a prompt diagnosis and appropriate treatment of pituitary deficiencies are strongly recommended, also in this age range.

  7. Syndrome of hypogonadism in males

    OpenAIRE

    R V Rozhivanov

    2014-01-01

    Hypogonadism in men - a clinical and laboratory syndrome caused by decreased secretion of testosterone by the testes. Depending on the level of destruction of the hypothalamic-pituitary-gonadal axis we distinguish two main forms of hypogonadism: hypergonadotrophic or primary hypogonadism and hypogonadotropic or secondary hypogonadism, clinical manifestations, diagnosis and treatment of which are presented in this clinical lecture. Keywords: hypogonadism, testosterone, hypergonadotrophic hypog...

  8. Case report

    African Journals Online (AJOL)

    ebutamanya

    2016-04-27

    Apr 27, 2016 ... present a 36 year old gravida 5 para 4 at 27 weeks gestation with hepatocellular carcinoma and main complaint of abdominal pain. She had ... 2. Introduction. Hepatocellular cancer(HCC) is the commonest cause of all primary .... the hypothalamic-pituitary-gonadal axis, this may lead to a reduction in ...

  9. Effects of Environmentally Relevant Concentrations of Bisphenol A on the Fathead Minnow

    Science.gov (United States)

    Bisphenol A (BPA) is a wide-spread environmental contaminant of concern due, in part, to possible effects on the vertebrate hypothalamic-pituitary-gonadal (HPG) axis, including activation of the estrogen receptor (ER). There is a reasonable amount of toxicological information fo...

  10. [Neuroendocrine and nutritional aspects of overtraining].

    Science.gov (United States)

    Rogero, Marcelo Macedo; Mendes, Renata Rebello; Tirapegui, Julio

    2005-06-01

    The overtraining syndrome is characterized by an excessive training that results in several adverse effects the main of which being the decay in performance. Its incidence among elite athletes has been experiencing a significant increase lately, which prompted a rush of interest in the search for efficient measures to prevent and treat this condition. It is necessary, however, to clarify possible mechanisms involved in the development of overtraining. Several hypothesis are being proposed, such as a greater activation of both the autonomic nervous system and the hypothalamic-pituitary-adrenal axis, and suppression of the hypothalamic-pituitary-gonadal axis. On the contrary, some studies suggest that the modulation of such systems is but a consequence of the overtraining syndrome and not its cause. Thus, recent hypothesis related to cytokine release, to central fatigue, to depletion of muscle and liver glycogen, and to a reduction in glutamine availability during physical activity are being raised.

  11. [Erectile Dysfunction in Diabetic Men - Current Diagnostics and Therapy].

    Science.gov (United States)

    Zitzmann, M; Kliesch, S

    2015-07-01

    Sexual functional dysfunctions represent a multidimensional nosological entity. Apart from the directly measurable pathophysiological parameters, psychological and dynamic partnership aspects are almost always involved. These can exert a triggering and a potentiating influence. Similarly, sociocultural factors have to be taken into account. In men the problem most frequently has a physiological focus and the main symptom within the complex of sexual difficulties, especially for diabetic patients, is erectile dysfunction. Disorders of ejaculation and orgasm may also occur. Testosterone production in men may be impaired due to obesity-related dysfunctions of the hypothalamic-pituitary-gonadal axis and this can lead to a clinically significant androgen deficit and thus also to a decline of libido. © Georg Thieme Verlag KG Stuttgart · New York.

  12. Involvement of the hypothalamic-pituitary-thyroid axis and its interaction with the hypothalamic-pituitary-adrenal axis in the ontogeny of avian thermoregulation: a review

    NARCIS (Netherlands)

    Debonne, M.; Baarendse, P.J.J.; Brand, van den H.; Kemp, B.; Bruggeman, V.; Decuypere, E.

    2008-01-01

    The emergence of thermoregulation in avian species is a complex matter in which neural as well as hormonal processes are involved. In a previous paper, the neural aspects of primary avian thermoregulation were discussed. In this paper the role of the hypothalamus-pituitary-thyroid axis (HPT-axis)

  13. A Role for Glucocorticoids in Stress-Impaired Reproduction: Beyond the Hypothalamus and Pituitary

    OpenAIRE

    Whirledge, Shannon; Cidlowski, John A.

    2013-01-01

    In addition to the well-characterized role of the sex steroid receptors in regulating fertility and reproduction, reproductive events are also mediated by the hypothalamic-pituitary-adrenal axis in response to an individual's environment. Glucocorticoid secretion in response to stress contributes to the well-characterized suppression of the hypothalamic-pituitary-gonadal axis through central actions in the hypothalamus and pituitary. However, both animal and in vitro studies indicate that oth...

  14. Endocannabinoids and the Endocrine System in Health and Disease.

    Science.gov (United States)

    Hillard, Cecilia J

    2015-01-01

    Some of the earliest reports of the effects of cannabis consumption on humans were related to endocrine system changes. In this review, the effects of cannabinoids and the role of the CB1 cannabinoid receptor in the regulation of the following endocrine systems are discussed: the hypothalamic-pituitary-gonadal axis, prolactin and oxytocin, thyroid hormone and growth hormone, and the hypothalamic-pituitary-adrenal axis. Preclinical and human study results are presented.

  15. Serum inhibin A and inhibin B in central precocious puberty before and during treatment with GnRH agonists

    DEFF Research Database (Denmark)

    Sehested, A; Andersson, A M; Müller, J

    2000-01-01

    Serum levels of the gonadal hormones inhibin A and inhibin B are undetectable or low in prepubertal girls, and rise during puberty. In girls with central precocious puberty (CPP) the hypothalamic-pituitary-gonadal axis is prematurely activated, if the girl is thereafter treated with GnRH agonists...... both gonadotropins and estradiol levels become suppressed. We therefore investigated serum levels of inhibin A and inhibin B in girls with CPP at diagnosis and during treatment in order to test the hypothesis that inhibin secretion would increase and decrease in parallel with the activation...... and suppression of the hypothalamic-pituitary-gonadal axis. Serum levels of inhibin A and inhibin B were significantly (p 0.0005) elevated in 42 girls at diagnosis of CPP (inhibin A: 7 pg/ml (...

  16. Serum inhibin A and inhibin B in central precocious puberty before and during treatment with GnRH agonists

    DEFF Research Database (Denmark)

    Sehested, A; Andersson, A M; Müller, J

    2000-01-01

    both gonadotropins and estradiol levels become suppressed. We therefore investigated serum levels of inhibin A and inhibin B in girls with CPP at diagnosis and during treatment in order to test the hypothesis that inhibin secretion would increase and decrease in parallel with the activation......Serum levels of the gonadal hormones inhibin A and inhibin B are undetectable or low in prepubertal girls, and rise during puberty. In girls with central precocious puberty (CPP) the hypothalamic-pituitary-gonadal axis is prematurely activated, if the girl is thereafter treated with GnRH agonists...... and suppression of the hypothalamic-pituitary-gonadal axis. Serum levels of inhibin A and inhibin B were significantly (p 0.0005) elevated in 42 girls at diagnosis of CPP (inhibin A: 7 pg/ml (...

  17. Hormonal changes in hemodialysis patients: Novel risk factors for mortality?

    Science.gov (United States)

    Gungor, Ozkan; Kocyigit, Ismail; Carrero, Juan Jesus; Yılmaz, Mahmut Ilker

    2017-09-01

    Patients with end-stage renal disease undergoing dialysis commonly experience derangements in the hypothalamic-pituitary-gonadal axis together with alterations at the level of synthesis and clearance of many hormones. This hormonal imbalance, even if asymptomatic, has recently been associated with increased mortality in these patients. In this review, we summarize observational and mechanistic evidence linking hormonal alterations at the level of the thyroid and sex-hormone systems with this mortality risks. © 2017 Wiley Periodicals, Inc.

  18. Disease: H00937 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available sexual characteristics in girls younger than 8 years old and in boys younger than 9 and a half years old. Ce...results from premature activation of the hypothalamic-pituitary-gonadal axis (HPG). CEPREPU is much more fre...quent in girls than in boys (up to 20:1 ratio). Recently, kisspeptin receptor (KISS1R) and its ligand, kissp

  19. Micropenis

    OpenAIRE

    Jeremy Wiygul; Lane S. Palmer

    2011-01-01

    Micropenis is part of a larger group of conditions broadly known as inconspicuous penis; however, it is fundamentally different from the other diagnoses in this group, such as webbed penis and buried penis, in that the underlying problem is the size of the penis itself, not with the surrounding and overlying skin. This condition is usually the result of a defect in the hypothalamic-pituitary-gonadal axis, although iatrogenic causes are identified infrequently. Management revolves around testo...

  20. Syndrome of hypogonadism in males

    Directory of Open Access Journals (Sweden)

    R V Rozhivanov

    2014-06-01

    Full Text Available Hypogonadism in men - a clinical and laboratory syndrome caused by decreased secretion of testosterone by the testes. Depending on the level of destruction of the hypothalamic-pituitary-gonadal axis we distinguish two main forms of hypogonadism: hypergonadotrophic or primary hypogonadism and hypogonadotropic or secondary hypogonadism, clinical manifestations, diagnosis and treatment of which are presented in this clinical lecture. Keywords: hypogonadism, testosterone, hypergonadotrophic hypogonadism, hypogonadotropic hypogonadism, treatment.

  1. A Role for Glucocorticoids in Stress-Impaired Reproduction: Beyond the Hypothalamus and Pituitary

    Science.gov (United States)

    Whirledge, Shannon

    2013-01-01

    In addition to the well-characterized role of the sex steroid receptors in regulating fertility and reproduction, reproductive events are also mediated by the hypothalamic-pituitary-adrenal axis in response to an individual's environment. Glucocorticoid secretion in response to stress contributes to the well-characterized suppression of the hypothalamic-pituitary-gonadal axis through central actions in the hypothalamus and pituitary. However, both animal and in vitro studies indicate that other components of the reproductive system are also regulated by glucocorticoids. Furthermore, in the absence of stress, it appears that homeostatic glucocorticoid signaling plays a significant role in reproduction and fertility in all tissues comprising the hypothalamic-pituitary-gonadal axis. Indeed, as central regulators of the immune response, glucocorticoids are uniquely poised to integrate an individual's infectious, inflammatory, stress, nutritional, and metabolic status through glucocorticoid receptor signaling in target tissues. Endocrine signaling between tissues regulating the immune and stress response and those determining reproductive status provides an evolutionary advantage, facilitating the trade-off between reproductive investment and offspring fitness. This review focuses on the actions of glucocorticoids in tissues important for fertility and reproduction, highlighting recent studies that show glucocorticoid signaling plays a significant role throughout the hypothalamic-pituitary-gonadal axis and characterizing these effects as permissive or inhibitory in terms of facilitating reproductive success. PMID:24064362

  2. Involvement of CCR6/CCL20/IL-17 Axis in NSCLC Disease Progression

    Science.gov (United States)

    Amir, Gail; Demma, Jonathan; Vernea, Fiona; Beider, Katia; Shlomai, Zippora; Wald, Hanna; Zamir, Gideon; Shapira, Oz M.; Peled, Amnon; Wald, Ori

    2011-01-01

    Objectives Autocrine and paracrine chemokine/chemokine receptor-based interactions promote non-small-cell-lung-cancer (NSCLC) carcinogenesis. CCL20/CCR6 interactions are involved in prostatic and colonic malignancy pathogenesis. The expression and function of CCL20/CCR6 and its related Th-17 type immune response in NSCLC is not yet defined. We sought to characterize the role of the CCL20/CCR6/IL-17 axis in NSCLC tumor growth. Methods A specialized histopathologist blindly assessed CCL20/CCR6 expression levels in 49 tissue samples of NSCLC patients operated in our department. Results were correlated to disease progression. Colony assays, ERK signaling and chemokine production were measured to assess cancer cell responsiveness to CCL20 and IL-17 stimulation. Results CCL20 was highly expressed in the majority (38/49, 77.5%) of tumor samples. Only a minority of samples (8/49, 16.5%) showed high CCR6 expression. High CCR6 expression was associated with a shorter disease-free survival (P = 0.008) and conferred a disease stage-independent 4.87-fold increased risk for disease recurrence (P = 0.0076, CI 95% 1.52–15.563). Cancerous cell colony-forming capacity was increased by CCL20 stimulation; this effect was dependent in part on ERK phosphorylation and signaling. IL-17 expression was detected in NSCLC; IL-17 potentiated the production of CCL20 by cancerous cells. Conclusion Our findings suggest that the CCL20/CCR6 axis promotes NSCLC disease progression. CCR6 is identified as a potential new prognostic marker and the CCL20/CCR6/IL-17 axis as a potential new therapeutic target. Larger scale studies are required to consolidate these observations. PMID:21949768

  3. Income inequality, gene expression, and brain maturation during adolescence

    OpenAIRE

    Parker, Nadine; Wong, Angelita Pui-Yee; Leonard, Gabriel; Perron, Michel; Pike, Bruce; Richer, Louis; Veillette, Suzanne; Pausova, Zdenka; Paus, Tomas

    2017-01-01

    Income inequality is associated with poor health and social outcomes. Negative social comparisons and competition may involve the hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonadal (HPG) axes in underlying some of these complex inter-relationships. Here we investigate brain maturation, indexed by age-related decreases in cortical thickness, in adolescents living in neighborhoods with differing levels of income inequality and household income. We examine whether inter-regi...

  4. Involvement of p38-βTrCP-Tristetraprolin-TNFα axis in radiation pneumonitis.

    Science.gov (United States)

    Krishnamurthy, Pranathi Meda; Shukla, Shirish; Ray, Paramita; Mehra, Rohit; Nyati, Mukesh K; Lawrence, Theodore S; Ray, Dipankar

    2017-07-18

    Early release of tumor necrosis factor-alpha (TNF-α) during radiotherapy of thoracic cancers plays an important role in radiation pneumonitis, whose inhibition may provide lung radioprotection. We previously reported radiation inactivates Tristetraprolin (TTP), a negative regulator of TNF-α synthesis, which correlated with increased TNF-α release. However, the molecular events involved in radiation-induced TTP inactivation remain unclear. To determine if eliminating Ttp in mice resulted in a phenotypic response to radiation, Ttp-null mice lungs were exposed to a single dose of 15 Gy, and TNF-α release and lung inflammation were analyzed at different time points post-irradiation. Ttp-/- mice with elevated (9.5±0.6 fold) basal TNF-α showed further increase (12.2±0.9 fold, pacute lung inflammation within a week post-irradiation. Further studies using mouse lung macrophage (MH-S), human lung fibroblast (MRC-5), and exogenous human TTP overexpressing U2OS and HEK293 cells upon irradiation (a single dose of 4 Gy) promoted p38-mediated TTP phosphorylation at the serine 186 position, which primed it to be recognized by an ubiquitin ligase (E3), beta transducing repeat containing protein (β-TrCP), to promote polyubiquitination-mediated proteasomal degradation. Consequently, a serine 186 to alanine (SA) mutant of TTP was resistant to radiation-induced degradation. Similarly, either a p38 kinase inhibitor (SB203580), or siRNA-mediated β-TrCP knockdown, or overexpression of dominant negative Cullin1 mutants protected TTP from radiation-induced degradation. Consequently, SB203580 pretreatment blocked radiation-induced TNF-α release and radioprotected macrophages. Together, these data establish the involvement of the p38-βTrCP-TTP-TNFα signaling axis in radiation-induced lung inflammation and identified p38 inhibition as a possible lung radioprotection strategy.

  5. Cocaine-mediated induction of microglial activation involves the ER stress-TLR2 axis.

    Science.gov (United States)

    Liao, Ke; Guo, Minglei; Niu, Fang; Yang, Lu; Callen, Shannon E; Buch, Shilpa

    2016-02-09

    ROS-ER stress-ATF4-TLR2 axis. Understanding the mechanism(s) involved in cocaine-mediated up-regulation of ROS-ER stress/TLR2 expression and microglial activation could have implications for the development of potential therapeutic targets aimed at resolving neuroinflammation in cocaine abusers.

  6. FXR-Gankyrin axis is involved in development of pediatric liver cancer.

    Science.gov (United States)

    Valanejad, Leila; Lewis, Kyle; Wright, Mary; Jiang, Yanjun; D'Souza, Amber; Karns, Rebekah; Sheridan, Rachel; Gupta, Anita; Bove, Kevin; Witte, David; Geller, James; Tiao, Gregory; Nelson, David L; Timchenko, Lubov; Timchenko, Nikolai

    2017-07-01

    The development of hepatoblastoma (HBL) is associated with failure of hepatic stem cells (HSC) to differentiate into hepatocytes. Despite intensive investigations, mechanisms of the failure of HSC to differentiate are not known. We found that oncogene Gankyrin (Gank) is involved in the inhibition of differentiation of HSC via triggering degradation of tumor suppressor proteins (TSPs) Rb, p53, C/EBPα and HNF4α. Our data show that the activation of a repressor of Gank, farnesoid X receptor, FXR, after initiation of liver cancer by Diethylnitrosamine (DEN) prevents the development of liver cancer by inhibiting Gank and rescuing tumor suppressor proteins. We next analyzed FXR-Gank-Tumor suppressor pathways in a large cohort of HBL patients which include 6 controls and 53 HBL samples. Systemic analysis of these samples and RNA-Seq approach revealed that the FXR-Gank axis is activated; markers of hepatic stem cells are dramatically elevated and hepatocyte markers are reduced in HBL samples. In the course of these studies, we found that RNA binding protein CUGBP1 is a new tumor suppressor protein which is reduced in all HBL samples. Therefore, we generated CUGBP1 KO mice and examined HBL signatures in the liver of these mice. Micro-array studies revealed that the HBL-specific molecular signature is developed in livers of CUGBP1 KO mice at very early ages. Thus, we conclude that FXR-Gank-TSPs-Stem cells pathway is a key determinant of liver cancer in animal models and in pediatric liver cancer. Our data provide a strong basis for development of FXR-Gank-based therapy for treatment of patients with hepatoblastoma. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  7. Neurosteroids, immunosteroids, and the Balkanization of endocrinology.

    Science.gov (United States)

    Schmidt, Kim L; Pradhan, Devaleena S; Shah, Amit H; Charlier, Thierry D; Chin, Eunice H; Soma, Kiran K

    2008-07-01

    Traditionally, the production and regulation of steroid hormones has been viewed as a multi-organ process involving the hypothalamic-pituitary-gonadal (HPG) axis for sex steroids and the hypothalamic-pituitary-adrenal (HPA) axis for glucocorticoids. However, active steroids can also be synthesized locally in target tissues, either from circulating inactive precursors or de novo from cholesterol. Here, we review recent work demonstrating local steroid synthesis, with an emphasis on steroids synthesized in the brain (neurosteroids) and steroids synthesized in the immune system (immunosteroids). Furthermore, recent evidence suggests that other components of the HPG axis (luteinizing hormone and gonadotropin-releasing hormone) and HPA axis (adrenocorticotropic hormone and corticotropin-releasing hormone) are expressed locally in target tissues, potentially providing a mechanism for local regulation of neurosteroid and immunosteroid synthesis. The balance between systemic and local steroid signals depends critically on life history stage, species adaptations, and the costs of systemic signals. During particular life history stages, there can be a shift from systemic to local steroid signals. We propose that the shift to local synthesis and regulation of steroids within target tissues represents a "Balkanization" of the endocrine system, whereby individual tissues and organs may become capable of autonomously synthesizing and modulating local steroid signals, perhaps independently of the HPG and HPA axes.

  8. Polaris, a Protein Involved in Left-Right Axis Patterning, Localizes to Basal Bodies and Cilia

    OpenAIRE

    Taulman, Patrick D.; Haycraft, Courtney J.; Balkovetz, Daniel F.; Yoder, Bradley K.

    2001-01-01

    Mutations in Tg737 cause a wide spectrum of phenotypes, including random left-right axis specification, polycystic kidney disease, liver and pancreatic defects, hydrocephalus, and skeletal patterning abnormalities. To further assess the biological function of Tg737 and its role in the mutant pathology, we identified the cell population expressing Tg737 and determined the subcellular localization of its protein product called Polaris. Tg737 expression is associated ...

  9. The involvement of noradrenergic mechanisms in the suppressive effects of diazepam on the hypothalamicpituitary- adrenal axis activity in female rats

    OpenAIRE

    Švob Štrac, Dubravka; Muck-Šeler, Dorotea

    2012-01-01

    Aim To elucidate the involvement of noradrenergic system in the mechanism by which diazepam suppresses basal hypothalamic-pituitary-adrenal (HPA) axis activity. Methods Plasma corticosterone and adrenocorticotropic hormone (ACTH) levels were determined in female rats treated with diazepam alone, as well as with diazepam in combination with clonidine (α2-adrenoreceptor agonist), yohimbine (α2-adrenoreceptor antagonist), alpha-methylp- tyrosine (α-MPT, an inhibitor of ca...

  10. Causes, consequences and biomarkers of stress in swine: an update.

    Science.gov (United States)

    Martínez-Miró, Silvia; Tecles, Fernando; Ramón, Marina; Escribano, Damián; Hernández, Fuensanta; Madrid, Josefa; Orengo, Juan; Martínez-Subiela, Silvia; Manteca, Xavier; Cerón, José Joaquín

    2016-08-19

    In recent decades there has been a growing concern about animal stress on intensive pig farms due to the undesirable consequences that stress produces in the normal physiology of pigs and its effects on their welfare and general productive performance. This review analyses the most important types of stress (social, environmental, metabolic, immunological and due to human handling), and their biological consequences for pigs. The physio-pathological changes associated with stress are described, as well as the negative effects of stress on pig production. In addition an update of the different biomarkers used for the evaluation of stress is provided. These biomarkers can be classified into four groups according to the physiological system or axis evaluated: sympathetic nervous system, hypothalamic-pituitary-adrenal axis, hypothalamic-pituitary-gonadal axis and immune system. Stress it is a process with multifactorial causes and produces an organic response that generates negative effects on animal health and production. Ideally, a panel of various biomarkers should be used to assess and evaluate the stress resulting from diverse causes and the different physiological systems involved in the stress response. We hope that this review will increase the understanding of the stress process, contribute to a better control and reduction of potential stressful stimuli in pigs and, finally, encourage future studies and developments to better monitor, detect and manage stress on pig farms.

  11. Crossover of the hypothalamic pituitary-adrenal/interrenal (HPA, -thyroid (HPT, and -gonadal (HPG axes in testicular development

    Directory of Open Access Journals (Sweden)

    Diana C. Castañeda Cortés

    2014-08-01

    Full Text Available Besides the well-known function of thyroid hormones (THs for regulating metabolism, it has recently been discovered that THs are also involved in testicular development in mammalian and non-mammalian species. THs, in combination with follicle stimulating hormone (FSH, lead to androgen synthesis in Denio rerio, which results in the onset of spermatogenesis in the testis, potentially relating the hypothalamic-pituitary-thyroid gland (HPT to the hypothalamic-pituitary-gonadal (HPG axes. Furthermore, studies in non-mammalian species have suggested that by stimulating the thyroid-stimulating hormone (TSH, THs can be induced by corticotropin-releasing hormone (CRH. This suggests that the hypothalamic-pituitary-adrenal/interrenal gland (HPA axis might influence the HPT axis. Additionally, it was shown that hormones pertaining to both HPT and HPA could also influence the HPG endocrine axis. For example, high levels of androgens were observed in the testis in Odonthestes bonariensis during a period of stress-induced sex determination, which suggests that stress hormones influence the gonadal fate towards masculinization. Thus, this review highlights the hormonal interactions observed between the HPT, HPA and HPG axes using a comparative approach in order to better understand how these endocrine systems could interact with each other to influence the development of testes.

  12. Regulation of energy balance by a gut-brain axis and involvement of the gut microbiota.

    Science.gov (United States)

    Bauer, Paige V; Hamr, Sophie C; Duca, Frank A

    2016-02-01

    Despite significant progress in understanding the homeostatic regulation of energy balance, successful therapeutic options for curbing obesity remain elusive. One potential target for the treatment of obesity is via manipulation of the gut-brain axis, a complex bidirectional communication system that is crucial in maintaining energy homeostasis. Indeed, ingested nutrients induce secretion of gut peptides that act either via paracrine signaling through vagal and non-vagal neuronal relays, or in an endocrine fashion via entry into circulation, to ultimately signal to the central nervous system where appropriate responses are generated. We review here the current hypotheses of nutrient sensing mechanisms of enteroendocrine cells, including the release of gut peptides, mainly cholecystokinin, glucagon-like peptide-1, and peptide YY, and subsequent gut-to-brain signaling pathways promoting a reduction of food intake and an increase in energy expenditure. Furthermore, this review highlights recent research suggesting this energy regulating gut-brain axis can be influenced by gut microbiota, potentially contributing to the development of obesity.

  13. Congenital Hypogonadotropic Hypogonadism and Kallmann Syndrome: Past, Present, and Future

    Directory of Open Access Journals (Sweden)

    Soo-Hyun Kim

    2015-12-01

    Full Text Available The proper development and coordination of the hypothalamic-pituitary-gonadal (HPG axis are essential for normal reproductive competence. The key factor that regulates the function of the HPG axis is gonadotrophin-releasing hormone (GnRH. Timely release of GnRH is critical for the onset of puberty and subsequent sexual maturation. Misregulation in this system can result in delayed or absent puberty and infertility. Congenital hypogonadotropic hypogonadism (CHH and Kallmann syndrome (KS are genetic disorders that are rooted in a GnRH deficiency but often accompanied by a variety of non-reproductive phenotypes such as the loss of the sense of smell and defects of the skeleton, eye, ear, kidney, and heart. Recent progress in DNA sequencing technology has produced a wealth of information regarding the genetic makeup of CHH and KS patients and revealed the resilient yet complex nature of the human reproductive neuroendocrine system. Further research on the molecular basis of the disease and the diverse signal pathways involved will aid in improving the diagnosis, treatment, and management of CHH and KS patients as well as in developing more precise genetic screening and counseling regime.

  14. Exercise and female adolescents: effects on the reproductive and skeletal systems.

    Science.gov (United States)

    Warren, M P; Stiehl, A L

    1999-01-01

    It is generally accepted that exercise is beneficial for young women, since it increases cardiovascular fitness and reduces adiposity. Too much exercise can have negative effects on the reproductive and skeletal systems, however, including primary and secondary amenorrhea thought to be caused by several factors including low body weight and improper nutrition. Primary and secondary amenorrhea present similar patterns of luteinizing hormone and follicle stimulating hormone suppression, probably involving the hypothalamic-pituitary-gonadal axis and possibly also the hypothalamic-pituitary-adrenal axis. Recent research has also suggested that leptin (a hormone made by the fat cell) is a possible link between menstrual cycles and fat and energy levels. The female athletic triad consists of three interrelated problems: eating disorders, amenorrhea, and osteopenia. The most serious aspect of hypoestrogenism is its effect on bone growth of elite athletes; those with delayed menarche show a higher incidence of scoliosis, stress fractures, and osteopenia than do girls with normal menarche. The higher incidence of bone problems may be linked to a lower rate of bone accretion, which may lead to lower peak bone mass. Unfortunately, the loss may be irreversible. In addition to decreasing training and gaining weight, treatment for menarcheal delay may include oral contraceptive therapy.

  15. Congenital Hypogonadotropic Hypogonadism and Kallmann Syndrome: Past, Present, and Future

    Science.gov (United States)

    2015-01-01

    The proper development and coordination of the hypothalamic-pituitary-gonadal (HPG) axis are essential for normal reproductive competence. The key factor that regulates the function of the HPG axis is gonadotrophin-releasing hormone (GnRH). Timely release of GnRH is critical for the onset of puberty and subsequent sexual maturation. Misregulation in this system can result in delayed or absent puberty and infertility. Congenital hypogonadotropic hypogonadism (CHH) and Kallmann syndrome (KS) are genetic disorders that are rooted in a GnRH deficiency but often accompanied by a variety of non-reproductive phenotypes such as the loss of the sense of smell and defects of the skeleton, eye, ear, kidney, and heart. Recent progress in DNA sequencing technology has produced a wealth of information regarding the genetic makeup of CHH and KS patients and revealed the resilient yet complex nature of the human reproductive neuroendocrine system. Further research on the molecular basis of the disease and the diverse signal pathways involved will aid in improving the diagnosis, treatment, and management of CHH and KS patients as well as in developing more precise genetic screening and counseling regime. PMID:26790381

  16. Modulation of immune responses in stress by Yoga

    Directory of Open Access Journals (Sweden)

    Arora Sarika

    2008-01-01

    Full Text Available Stress is a constant factor in today′s fastpaced life that can jeopardize our health if left unchecked. It is only in the last half century that the role of stress in every ailment from the common cold to AIDS has been emphasized, and the mechanisms involved in this process have been studied. Stress influences the immune response presumably through the activation of the hypothalamic-pituitary adrenal axis, hypothalamic pituitary-gonadal axis, and the sympathetic-adrenal-medullary system. Various neurotransmitters, neuropeptides, hormones, and cytokines mediate these complex bidirectional interactions between the central nervous system (CNS and the immune system. The effects of stress on the immune responses result in alterations in the number of immune cells and cytokine dysregulation. Various stress management strategies such as meditation, yoga, hypnosis, and muscle relaxation have been shown to reduce the psychological and physiological effects of stress in cancers and HIV infection. This review aims to discuss the effect of stress on the immune system and examine how relaxation techniques such as Yoga and meditation could regulate the cytokine levels and hence, the immune responses during stress.

  17. Early Life Exposure to Ractopamine Causes Endocrine-Disrupting Effects in Japanese Medaka (Oryzias latipes).

    Science.gov (United States)

    Sun, Liwei; Wang, Sisi; Lin, Xia; Tan, Hana; Fu, Zhengwei

    2016-02-01

    β-Agonists, which are used as human pharmaceuticals or feed additives, have been detected in aquatic environments. β-Agonists have also been proposed for use in aquaculture. However, there are limited data available regarding the adverse effects of β-agonists in aquatic organisms. In this study, ractopamine was selected as the representative β-agonist, and medaka embryos were exposed at concentrations ranging from 5 to 625 μg/L for 44 days. In contrast to what has been found in mammals, ractopamine caused no growth response in medaka. However, the transcriptional changes of genes related to the hypothalamic-pituitary-gonadal (HPG) axis, especially in females, suggested that β-agonists may have the potential to disrupt the endocrine system. Moreover, genes involved in anti-oxidative activity or detoxification were affected in a gender-specific manner. These findings, particularly the effects on the endocrine system of fish, will advance our understanding of the ecotoxicity of β-agonists.

  18. Endocrine and Metabolic Aspects of OSA

    Directory of Open Access Journals (Sweden)

    Ravinder Goswami

    2014-03-01

    Full Text Available Obstructive sleep apnea (OSA is characterized by repeated spells of apnea.Collapsibility of hypopharynx due to multiple factors involving pharyngeal dilatormuscles and deposition of fat or fluid in the surrounding soft tissues are importantcontributing factors in its pathogenesis. OSA commonly affects obese individuals.Males are more commonly affected than the females probably due to the disturbingeffect of testosterone on sleep.The impact of OSA on human health include disturbances in endocrine and metabolicsystem affecting hypothalamic-pituitary-gonadal axis, adrenocorticotrophic-cortisolaxis, growth hormone, antidiuretic hormones and insulin resistance. There is atendency for predisposition of the metabolic syndrome or its components includingglycemic dysregulation, hypertension, hyperlipidemia and physical parameters relatedto adiposity. On the other hand, several endocrine disorders such as hypothyroidism,growth hormone excess, polycystic ovarian disease and testosterone replacement areassociated with increased prevalence of OSA.There is limited information on the effect of treatment of OSA by continuous positiveairway pressure (CPAP on the endocrine and metabolic disturbances. There is a needto conduct randomized controlled trials using CPAP therapy in patients with OSA andto study its cause and effect relationship with endocrine and metabolic disturbances.

  19. PARALLELS BETWEEN MAJOR DEPRESSIVE DISORDER AND ALZHEIMER’S DISEASE: ROLE OF OXIDATIVE STRESS AND GENETIC VULNERABILITY

    Science.gov (United States)

    Rodrigues, Roberto; Petersen, Robert B.

    2014-01-01

    The thesis of this review is that oxidative stress is the central factor in major depressive disorder (MDD) and Alzheimer’s disease (AD). The major elements involved are inflammatory cytokines, the hypothalamic pituitary axis, the hypothalamic pituitary gonadal, and arginine vasopressin systems, which induce glucocorticoid and “oxidopamatergic” cascades when triggered by psychosocial stress, severe life threatening events, and mental-affective and somatic diseases. In individuals with a genomic vulnerability to depression these cascades may result in chronic depression-anxiety-stress spectra, resulting in MDD and other known depressive syndromes. In contrast, in subjects with genomic vulnerability to Alzheimer’s disease, oxidative stress-induced brain damage triggers specific antioxidant defenses, i.e. increased levels of amyloid-β (Aβ) and aggregation of hyper-phosphorylated tau, resulting in paired helical filaments and impaired functions related to the ApoEε4 isoform, leading to complex pathological cascades culminating in AD. Surprisingly, all the AD associated molecular pathways mentioned in this review have been shown to be similar or analogous to those found in depression, including structural damage, i.e. hippocampal and frontal cortex atrophy. Other interacting molecular signals, i.e. GSK-3β, convergent survival factors (brain-derived neurotrophic factor and heat shock proteins), and transition-redox metals are also mentioned to emphasize the vast array of intermediates that could interact via comparable mechanisms in both MDD and AD. PMID:24927694

  20. Targeted Disruption of ALK Reveals a Potential Role in Hypogonadotropic Hypogonadism.

    Science.gov (United States)

    Witek, Barbara; El Wakil, Abeer; Nord, Christoffer; Ahlgren, Ulf; Eriksson, Maria; Vernersson-Lindahl, Emma; Helland, Åslaug; Alexeyev, Oleg A; Hallberg, Bengt; Palmer, Ruth H

    2015-01-01

    Mice lacking ALK activity have previously been reported to exhibit subtle behavioral phenotypes. In this study of ALK of loss of function mice we present data supporting a role for ALK in hypogonadotropic hypogonadism in male mice. We observed lower level of serum testosterone at P40 in ALK knock-out males, accompanied by mild disorganization of seminiferous tubules exhibiting decreased numbers of GATA4 expressing cells. These observations highlight a role for ALK in testis function and are further supported by experiments in which chemical inhibition of ALK activity with the ALK TKI crizotinib was employed. Oral administration of crizotinib resulted in a decrease of serum testosterone levels in adult wild type male mice, which reverted to normal levels after cessation of treatment. Analysis of GnRH expression in neurons of the hypothalamus revealed a significant decrease in the number of GnRH positive neurons in ALK knock-out mice at P40 when compared with control littermates. Thus, ALK appears to be involved in hypogonadotropic hypogonadism by regulating the timing of pubertal onset and testis function at the upper levels of the hypothalamic-pituitary gonadal axis.

  1. Targeted Disruption of ALK Reveals a Potential Role in Hypogonadotropic Hypogonadism.

    Directory of Open Access Journals (Sweden)

    Barbara Witek

    Full Text Available Mice lacking ALK activity have previously been reported to exhibit subtle behavioral phenotypes. In this study of ALK of loss of function mice we present data supporting a role for ALK in hypogonadotropic hypogonadism in male mice. We observed lower level of serum testosterone at P40 in ALK knock-out males, accompanied by mild disorganization of seminiferous tubules exhibiting decreased numbers of GATA4 expressing cells. These observations highlight a role for ALK in testis function and are further supported by experiments in which chemical inhibition of ALK activity with the ALK TKI crizotinib was employed. Oral administration of crizotinib resulted in a decrease of serum testosterone levels in adult wild type male mice, which reverted to normal levels after cessation of treatment. Analysis of GnRH expression in neurons of the hypothalamus revealed a significant decrease in the number of GnRH positive neurons in ALK knock-out mice at P40 when compared with control littermates. Thus, ALK appears to be involved in hypogonadotropic hypogonadism by regulating the timing of pubertal onset and testis function at the upper levels of the hypothalamic-pituitary gonadal axis.

  2. D-Aspartate Induces Proliferative Pathways in Spermatogonial GC-1 Cells.

    Science.gov (United States)

    Santillo, Alessandra; Falvo, Sara; Chieffi, Paolo; Di Fiore, Maria Maddalena; Senese, Rosalba; Chieffi Baccari, Gabriella

    2016-02-01

    D-aspartate (D-Asp) is an endogenous amino acid present in vertebrate tissues, with particularly high levels in the testis. In vivo studies indicate that D-Asp indirectly stimulates spermatogenesis through the hypothalamic-pituitary-gonadal axis. Moreover, in vitro studies have demonstrated that D-Asp up-regulates testosterone production in Leydig cells by enhancing expression of the steroidogenic acute regulatory protein. In this study, a cell line derived from immortalized type-B mouse spermatogonia retaining markers of mitotic germ cells (GC-1) was employed to explore more direct involvement of D-Asp in spermatogenesis. Activity and protein expression of markers of cell proliferation were determined at intervals during incubation in D-Asp-containing medium. D-Asp induced phosphorylation of ERK and Akt proteins, stimulated expression of PCNA and Aurora B, and enhanced mRNA synthesis and protein expression of P450 aromatase and protein expression of Estrogen Receptor β (ERβ). These results are the first demonstration of a direct effect of D-Asp on spermatogonial mitotic activity. Considering that spermatogonia express the NR1 subunit of the N-Methyl-D-Aspartic Acid receptor (NMDAR), we suggest that their response to D-Asp depends on NMDAR-mediated activation of the ERK and Akt pathways and is further enhanced by activation of the P450 aromatase/ERβ pathway. © 2015 Wiley Periodicals, Inc.

  3. Persistent amenorrhea and decreased DHEAS to cortisol ratio after recovery from anorexia nervosa.

    Science.gov (United States)

    Andrisani, Alessandra; Sabbadin, Chiara; Minardi, Silvia; Favaro, Angela; Donà, Gabriella; Bordin, Luciana; Ambrosini, Guido; Armanini, Decio

    2017-04-01

    Persistent amenorrhea is a frequent condition affecting anorexic patients after stable weight recovery. It has been proposed that it could be due to alterations of the hypothalamic-pituitary-gonadal axis linked with persistent hormonal impairments, such as relative hypercortisolemia and hypoleptinemia, and psychological symptoms related to anorexia nervosa (AN). The aim of our study was to evaluate the metabolic and hormonal pattern involved in the persistence of amenorrhea after recovery from AN. Eight weight-recovered anorexic patients with amenorrhea were investigated and matched with 10 healthy eumenorrhoic women, comparable for age and BMI. Data showed basal FSH and LH values similar in both groups and a normal pituitaric response to LHRH administration. Morning serum cortisol was normal but significantly higher in patients, while dehydroepiandrosterone sulfate (DHEAS) to cortisol ratio, leptin and vitamin D were significantly lower in patients than controls. Women with previous AN presented insulin resistance and two patients showed an overall picture consistent with polycystic ovary syndrome (PCOS). In conclusion, long-lasting amenorrhea after recovery from AN is linked with a persistent hypothalamic dysfunction, although other concomitant causes like PCOS and insulin resistance should be considered. Decreased DHEAS to cortisol ratio is a new finding which could be correlated to the persistent hypogonadism.

  4. Deleterious effects of obesity upon the hormonal and molecular mechanisms controlling spermatogenesis and male fertility.

    Science.gov (United States)

    Davidson, Lien M; Millar, Kate; Jones, Celine; Fatum, Muhammad; Coward, Kevin

    2015-09-01

    Worldwide obesity rates have nearly doubled since 1980 and currently over 10% of the population is obese. In 2008, over 1.4 billion adults aged 20 years and older had a body mass index or BMI above a healthy weight and of these, over 200 million men and nearly 300 million women were obese. While obesity can have many ramifications upon adult life, one growing area of concern is that of reproductive capacity. Obesity affects male infertility by influencing the hypothalamic-pituitary-gonadal axis, thus causing detrimental effects upon spermatogenesis and subsequent fertility. In particular, evidence indicates that excess adipose tissue can alter the relative ratio of testosterone and oestrogen. Additional effects involve the homeostatic disruption of insulin, sex-hormone-binding-globulin, leptin and inhibin B, leading to diminished testosterone production and impairment to spermatogenesis. Aberrant spermatogenesis arising from obesity is associated with downstream changes in key semen parameters, defective sperm capacitation and binding, and deleterious effects on sperm chromatin structure. More recent investigations into trans-generational epigenetic inheritance further suggest that molecular changes in sperm that arise from obesity-related impaired spermatogenesis, such as modified sperm RNA levels, DNA methylation, protamination and histone acetylation, can impact upon the development of offspring. Here, we summarise our current understanding of how obesity exerts influence over spermatogenesis and subsequent fertility status, and make recommendations for future investigative research.

  5. Involvement of brain-gut axis in treatment of cerebral infarction by β-asaron and paeonol.

    Science.gov (United States)

    He, Xiaogang; Cai, Qiufang; Li, Jianxiang; Guo, Weifeng

    2018-02-14

    Cerebral infarction (CI) causes severe brain damage with high incidence. This study aimed to investigate the involvement of brain-gut axis in the treatment of CI by combined administration of β-asaron and paeonol. Rat middle cerebral artery occlusion (MCAO) model was established, the interleukin-1beta (IL-1β) and tumor necrosis factor α (TNF-α) in the rat peripheral blood were determined by ELISA assay, and brain tissue damage was evaluated by TUNNEL assay. The correlation of cholecystokinin (CCK) and nuclear factor-kappaB (NF-κB) signaling components between intestinal mucosa and prefrontal cortex of MCAO rats treated with β-asaron and paeonol were analyzed by quantitative RT-PCR and western blotting. In vitro transwell co-culture was performed to confirm the correlated expression. The expression of CCK and NF-κB signaling components were closely correlated between the intestinal mucosa and prefrontal cortex of MCAO rats treated with β-asaron and paeonol. The combined administration also regulates the IL-1β and TNF-α in the MCAO rat peripheral blood and ameliorate the brain damage in MCAO rats. Elevated expression of related genes was observed in the cortical neurons co-cultured with intestinal mucosal epithelial cells treated by β-asaron and paeonol. The brain-gut axis mediates the therapeutic effect of β-asaron and paeonol for cerebral infarction through CCK and NF-κB signaling. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Interaction involving the thymus and the hypothalamus-pituitary axis, immunomodulation by hormones

    Directory of Open Access Journals (Sweden)

    Marković Ljiljana 2

    2004-01-01

    Full Text Available Perfectly projected and impeccably created, the endocrine system precisely regulates the most delicate immune processes. The immune and neuroendocrine systems are two essential physiological components of mammalian organisms important for protection from the infection and disease on one hand, and on the other, for regulation of metabolism and other physiological activities; namely, the evidence has been found indicating that there is active and dynamic collaboration of these systems in the execution of their designated functions [1, 2,4]. These interactions occur at many stages of embryonic and neonatal development, and they are a continual part of normal homeostatic balance necessary to preserve health. There is communication between neuroendocrine and immune system via cytokines, neurotransmitters and peptide hormones which act, in both systems, through the same receptor molecules (Scheme 1. Many investigators have reported the increased thymic weight in experimental animals due to both castration and adrenalectomy [4]. The discovery from 1898 revealing that thymus was enlarged in castrated rabbits has been considered the embryo of hybrid medical discipline, i.e. the immunoendocrinology [1]. In the actual literature, at least in that available to us, it has not been noted that the appearance of the eunuchs, i.e. the castrates, stimulated the analytical approach to this phenomenon. Endocrine influences appear to be a part of bidirectional circuitry, namely, thymic hormones also regulate the release of hormones from the pituitary gland. Physiologically, thymus is under neuroendocrine control. It is apparent that the circulating levels of distinct peptide hormones are necessary to maintain a series of biological functions related both to micro environmental and lymphoid cells of the organ. The neuroendocrine control of the thymus appears to be extremely complex, with apparent presence of complete intrathymic biological circuitry involving the

  7. A potential kidney-bone axis involved in the rapid minute-to-minute regulation of plasma Ca2+

    DEFF Research Database (Denmark)

    Nordholm, Anders; Mace, Maria L; Gravesen, Eva

    2015-01-01

    .41 ± 0.02 mM (p regulation of p-Ca(2+) independent of PTH, C-PTH and CT. CONCLUSIONS: P-Ca(2......-point' of p-Ca(2+) on bone surface, independently of PTH and calcitonin. Our results point toward existence of an as yet unknown factor/mechanism, which mediates the axis between kidney and bone, and which is involved in the very rapid regulation of p-Ca(2+).......BACKGROUND: Understanding the regulation of mineral homeostasis and function of the skeleton as buffer for Calcium and Phosphate has regained new interest with introduction of the syndrome "Chronic Kidney Disease-Mineral and Bone Disorder"(CKD-MBD). The very rapid minute-to-minute regulation...

  8. Bep4 protein is involved in patterning along the animal-vegetal axis in the Paracentrotus lividus embryo.

    Science.gov (United States)

    Romancino, D P; Montana, G; Dalmazio, S; Di Carlo, M

    2001-06-01

    In sea urchin embryos, the initial animal-vegetal (AV) axis is specified during oogenesis but the mechanism is largely unknown. By using chemical reagents such as lithium, it is possible to shift the principal embryonic territories toward a vegetal fate. We have investigated the possibility of obtaining the same morphological effect as with lithium by utilizing Fabs against the maternal Bep4 protein that is localized in the animal part of Paracentrotus lividus egg and embryos. Incubation of fertilized eggs with Fabs against Bep4 protein causes exogastrulation at 48 h of development of P. lividus embryos, similar to embryos treated with lithium. This vegetalizing effect was ascertained by utilizing territorial markers such as EctoV, EndoI, and Ig8. The effect of Fabs against Bep4 on gene expression was observed by monitoring spatial expression of the hatching enzyme gene. A decreased expression domain compared to its normal spatial distribution was detected and this effect was again comparable to those obtained with lithium treatment. Association of Bep4 with a cadherin was demonstrated by immunoprecipitation and immunostaining experiments, and an involvement in cell signaling is discussed. In addition, treatment of embryos with anti-Bep4 Fabs causes an enhancement in the level and an expansion in the pattern of nuclear beta-catenin. Moreover, this treatment also provokes a decrease of beta-catenin in adherens junctions. Together, these data indicate that anti-Bep4 Fabs provoke a shift of the animal-vegetal boundary toward the animal pole and suggest an active role of Bep4 protein in patterning along the AV axis. Copyright 2001 Academic Press.

  9. Hypogonadism: Its Prevalence and Diagnosis.

    Science.gov (United States)

    Ross, Anna; Bhasin, Shalender

    2016-05-01

    Hypogonadism is a clinical syndrome, which results from the failure of the testes to produce physiologic levels of testosterone and a normal number of spermatozoa due to defects at one or more levels of the hypothalamic-pituitary-gonadal axis. Primary hypogonadism results from malfunction at the level of the testes due to a genetic cause, injury, inflammation, or infection. Hypothalamic and/or pituitary failure leads to secondary hypogonadism, most often as a result of genetic defects, neoplasm, or infiltrative disorders. The signs and symptoms of hypogonadism depend on the age of onset, severity of androgen deficiency, and underlying cause of androgen deficiency. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. The corticotropin-releasing hormone network and the hypothalamic-pituitary-adrenal axis: molecular and cellular mechanisms involved.

    Science.gov (United States)

    Bonfiglio, Juan José; Inda, Carolina; Refojo, Damián; Holsboer, Florian; Arzt, Eduardo; Silberstein, Susana

    2011-01-01

    Corticotropin-releasing hormone (CRH) plays a key role in adjusting the basal and stress-activated hypothalamic-pituitary-adrenal axis (HPA). CRH is also widely distributed in extrahypothalamic circuits, where it acts as a neuroregulator to integrate the complex neuroendocrine, autonomic, and behavioral adaptive response to stress. Hyperactive and/or dysregulated CRH circuits are involved in neuroendocrinological disturbances and stress-related mood disorders such as anxiety and depression. This review describes the main physiological features of the CRH network and summarizes recent relevant information concerning the molecular mechanism of CRH action obtained from signal transduction studies using cells and wild-type and transgenic mice lines. Special focus is placed on the MAPK signaling pathways triggered by CRH through the CRH receptor 1 that plays an essential role in CRH action in pituitary corticotrophs and in specific brain structures. Recent findings underpin the concept of specific CRH-signaling pathways restricted to specific anatomical areas. Understanding CRH action at molecular levels will not only provide insight into the precise CRH mechanism of action, but will also be instrumental in identifying novel targets for pharmacological intervention in neuroendocrine tissues and specific brain areas involved in CRH-related disorders. Copyright © 2011 S. Karger AG, Basel.

  11. Factors involved in early polarization of the anterior-posterior axis in the milkweed bug Oncopeltus fasciatus.

    Science.gov (United States)

    Ginzburg, Neta; Cohen, Mira; Chipman, Ariel D

    2017-05-01

    The axes of insect embryos are defined early in the blastoderm stage. Genes involved in this polarization are well known in Drosophila, but less so in other insects, such as the milkweed bug Oncopeltus fasciatus. Using quantitative PCR, we looked at differential expression of several candidate genes for early anterior-posterior patterning and found that none of them are expressed asymmetrically in the early blastoderm. We then used an RNA-Seq approach to identify novel candidate genes that might be involved in early polarization in Oncopeltus. We focused on transcription factors (TFs) as these are likely to be central players in developmental processes. Using both homology and domain based identification approaches, we were unable to find any TF encoding transcripts that are expressed asymmetrically along the anterior-posterior axis at early stages. Using a GO-term analysis of all asymmetrically expressed mRNAs, we found an enrichment of genes relating to mitochondrial function in the posterior at the earliest studied time-point. We also found a gradual enrichment of transcription related activities, giving us a putative time frame for the maternal to zygotic transition. Our dataset provides us with a list of new candidate genes in early development, which can be followed up experimentally. © 2017 Wiley Periodicals, Inc.

  12. PCB disruption of the hypothalamus-pituitary-interrenal axis involves brain glucocorticoid receptor downregulation in anadromous Arctic charr

    Science.gov (United States)

    Aluru, N.; Jorgensen, E.H.; Maule, A.G.; Vijayan, M.M.

    2004-01-01

    We examined whether brain glucocorticoid receptor (GR) modulation by polychlorinated biphenyls (PCBs) was involved in the abnormal cortisol response to stress seen in anadromous Arctic charr (Salvelinus alpinus). Fish treated with Aroclor 1254 (0, 1, 10, and 100 mg/kg body mass) were maintained for 5 mo without feeding in the winter to mimic their seasonal fasting cycle, whereas a fed group with 0 and 100 mg/kg Aroclor was maintained for comparison. Fasting elevated plasma cortisol levels and brain GR content but depressed heat shock protein 90 (hsp90) and interrenal cortisol production capacity. Exposure of fasted fish to Aroclor 1254 resulted in a dose-dependent increase in brain total PCB content. This accumulation in fish with high PCB dose was threefold higher in fasted fish compared with fed fish. PCBs depressed plasma cortisol levels but did not affect in vitro interrenal cortisol production capacity in fasted charr. At high PCB dose, the brain GR content was significantly lower in the fasted fish and this corresponded with a lower brain hsp70 and hsp90 content. The elevation of plasma cortisol levels and upregulation of brain GR content may be an important adaptation to extended fasting in anadromous Arctic charr, and this response was disrupted by PCBs. Taken together, the hypothalamus-pituitary- interrenal axis is a target for PCB impact during winter emaciation in anadromous Arctic charr.

  13. Resveratrol ameliorates the anxiety- and depression-like behavior of subclinical hypothyroidism rat: possible involvement of the HPT axis, HPA axis, and Wnt/β-catenin pathway

    Directory of Open Access Journals (Sweden)

    Jinfang eGe

    2016-05-01

    Full Text Available Metabolic disease subclinical hypothyroidism (SCH is closely associated with depression-like behavior both in human and animal studies, and our previous studies have identified the antidepressant effect of resveratrol (RES in stressed rat model. The aim of this study was to investigate whether RES would manifest an antidepressant effect in SCH rat model and explore the possible mechanism. A SCH rat model was induced by hemi-thyroid electrocauterization, after which the model rats in the RES and LT4 groups received a daily intragastric injection of RES at the dose of 15 mg/kg or LT4 at the dose of 60 μg/kg for 16 days, respectively. The rats’ plasma concentrations of thyroid hormones were measured. Behavioral performance and hypothalamic-pituitary-adrenal (HPA activity were evaluated. The protein expression levels of the Wnt/β-catenin in the hippocampus were detected by western blot. The results showed that RES treatment down-regulated the elevated plasma thyroid stimulating hormone (TSH concentration and the hypothalamic mRNA expression of thyrotropin releasing hormone (TRH in the SCH rats. RES-treated rats showed increased rearing frequency and distance in the OFT, increased sucrose preference in the SPT, and decreased immobility in the FST compared with SCH rats. The ratio of the adrenal gland weight to body weight, the plasma corticosterone levels and the hypothalamic CRH mRNA expression were reduced in the RES-treated rats. Moreover, RES treatment up-regulated the relative ratio of phosphorylated-GSK3β (p-GSK3β/GSK3β and protein levels of p-GSK3β, cyclinD1 and c-myc, while down-regulating the relative ratio of phosphorylated-β-catenin (p-β-catenin/β-catenin and expression of GSK3β in the hippocampus. These findings suggest that RES exerts anxiolytic- and antidepressant-like effect in SCH rats by down-regulating hyperactivity of the HPA axis and regulating both the HPT axis and the Wnt/β-catenin pathway.

  14. Belinostat-induced apoptosis and growth inhibition in pancreatic cancer cells involve activation of TAK1-AMPK signaling axis

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Bing, E-mail: wangbin69@yahoo.com; Wang, Xin-bao; Chen, Li-yu; Huang, Ling; Dong, Rui-zen

    2013-07-19

    Highlights: •Belinostat activates AMPK in cultured pancreatic cancer cells. •Activation of AMPK is important for belinostat-induced cytotoxic effects. •ROS and TAK1 are involved in belinostat-induced AMPK activation. •AMPK activation mediates mTOR inhibition by belinostat. -- Abstract: Pancreatic cancer accounts for more than 250,000 deaths worldwide each year. Recent studies have shown that belinostat, a novel pan histone deacetylases inhibitor (HDACi) induces apoptosis and growth inhibition in pancreatic cancer cells. However, the underlying mechanisms are not fully understood. In the current study, we found that AMP-activated protein kinase (AMPK) activation was required for belinostat-induced apoptosis and anti-proliferation in PANC-1 pancreatic cancer cells. A significant AMPK activation was induced by belinostat in PANC-1 cells. Inhibition of AMPK by RNAi knockdown or dominant negative (DN) mutation significantly inhibited belinostat-induced apoptosis in PANC-1 cells. Reversely, AMPK activator AICAR and A-769662 exerted strong cytotoxicity in PANC-1 cells. Belinostat promoted reactive oxygen species (ROS) production in PANC-1 cells, increased ROS induced transforming growth factor-β-activating kinase 1 (TAK1)/AMPK association to activate AMPK. Meanwhile, anti-oxidants N-Acetyl-Cysteine (NAC) and MnTBAP as well as TAK1 shRNA knockdown suppressed belinostat-induced AMPK activation and PANC-1 cell apoptosis. In conclusion, we propose that belinostat-induced apoptosis and growth inhibition require the activation of ROS-TAK1-AMPK signaling axis in cultured pancreatic cancer cells.

  15. The involvement of noradrenergic mechanisms in the suppressive effects of diazepam on the hypothalamic-pituitary-adrenal axis activity in female rats.

    Science.gov (United States)

    Švob Štrac, Dubravka; Muck-Šeler, Dorotea; Pivac, Nela

    2012-06-01

    To elucidate the involvement of noradrenergic system in the mechanism by which diazepam suppresses basal hypothalamic-pituitary-adrenal (HPA) axis activity. Plasma corticosterone and adrenocorticotropic hormone (ACTH) levels were determined in female rats treated with diazepam alone, as well as with diazepam in combination with clonidine (α(2)-adrenoreceptor agonist), yohimbine (α(2)-adrenoreceptor antagonist), alpha-methyl-p-tyrosine (α-MPT, an inhibitor of catecholamine synthesis), or reserpine (a catecholamine depleting drug) and yohimbine. Diazepam administered in a dose of 2.0 mg/kg suppressed basal HPA axis activity, ie, decreased plasma corticosterone and ACTH levels. Pretreatment with clonidine or yohimbine failed to affect basal plasma corticosterone and ACTH concentrations, but abolished diazepam-induced inhibition of the HPA axis activity. Pretreatment with α-MPT, or with a combination of reserpine and yohimbine, increased plasma corticosterone and ACTH levels and prevented diazepam-induced inhibition of the HPA axis activity. The results suggest that α(2)-adrenoreceptors activity, as well as intact presynaptic noradrenergic function, are required for the suppressive effect of diazepam on the HPA axis activity.

  16. The involvement of noradrenergic mechanisms in the suppressive effects of diazepam on the hypothalamic-pituitary-adrenal axis activity in female rats

    Science.gov (United States)

    Švob Štrac, Dubravka; Muck-Šeler, Dorotea; Pivac, Nela

    2012-01-01

    Aim To elucidate the involvement of noradrenergic system in the mechanism by which diazepam suppresses basal hypothalamic-pituitary-adrenal (HPA) axis activity. Methods Plasma corticosterone and adrenocorticotropic hormone (ACTH) levels were determined in female rats treated with diazepam alone, as well as with diazepam in combination with clonidine (α2-adrenoreceptor agonist), yohimbine (α2-adrenoreceptor antagonist), alpha-methyl-p-tyrosine (α-MPT, an inhibitor of catecholamine synthesis), or reserpine (a catecholamine depleting drug) and yohimbine. Results Diazepam administered in a dose of 2.0 mg/kg suppressed basal HPA axis activity, ie, decreased plasma corticosterone and ACTH levels. Pretreatment with clonidine or yohimbine failed to affect basal plasma corticosterone and ACTH concentrations, but abolished diazepam-induced inhibition of the HPA axis activity. Pretreatment with α-MPT, or with a combination of reserpine and yohimbine, increased plasma corticosterone and ACTH levels and prevented diazepam-induced inhibition of the HPA axis activity. Conclusion The results suggest that α2-adrenoreceptors activity, as well as intact presynaptic noradrenergic function, are required for the suppressive effect of diazepam on the HPA axis activity. PMID:22661134

  17. The involvement of noradrenergic mechanisms in the suppressive effects of diazepam on the hypothalamic-pituitary-adrenal axis activity in female rats

    OpenAIRE

    Švob Štrac, Dubravka; Muck-Šeler, Dorotea; Pivac, Nela

    2012-01-01

    Aim To elucidate the involvement of noradrenergic system in the mechanism by which diazepam suppresses basal hypothalamic-pituitary-adrenal (HPA) axis activity. Methods Plasma corticosterone and adrenocorticotropic hormone (ACTH) levels were determined in female rats treated with diazepam alone, as well as with diazepam in combination with clonidine (α2-adrenoreceptor agonist), yohimbine (α2-adrenoreceptor antagonist), alpha-methyl-p-tyrosine (α-MPT, an inhibitor of catecholamine synthesis), ...

  18. Arginine-vasotocin expression and participation in reproduction and social behavior in males of the cichlid fish Cichlasoma dimerus.

    Science.gov (United States)

    Ramallo, Martín Roberto; Grober, Matthew; Cánepa, Maximiliano Martín; Morandini, Leonel; Pandolfi, Matías

    2012-11-01

    In non-mammalian vertebrates, the nonapeptide arginine-vasotocin (AVT) is involved in the regulation of social behavior related to reproduction and aggression. The cichlid fish Cichlasoma dimerus is a monogamous species with complex social hierarchies. Males are found in one of two basic alternative phenotypes: Non-territorial and territorial males. In this work we characterize the vasotocinergic system in males of C. dimerus in relation to social status with particular emphasis on the various putative sites of action of AVT across the hypothalamic-pituitary-gonad (HPG) axis, and its effects on reproductive and social behavior. The location and distribution of vasotocinergic neurons in the brain was studied, highlighting a morphometric analysis of AVT producing neurons in males of different social status. The effect of AVT on pituitary gonadotropin secretion was analyzed by single pituitary culture while expression of AVT in peripheral organs was studied by RT-PCR using specific primers. Finally, the role of AVT on testicular androgen release was assessed by in vitro incubation of testis. Results showed a positive effect of AVT on gonadotropin secretion, where β-LH showcased a triphasic response under increasing AVT concentration, while β-FSH's response was dose-dependent and directly proportional. AVT showed a positive and concentration-dependent effect over testicular androgens synthesis and secretion in vitro. Vasotocin expression was observed in testicular somatic tissue located in the interstitial compartment. Thus, the AVT system in C. dimerus appears to be of high complexity, with multiple sites of action in the hypothalamus-pituitary-gonadal axis. Copyright © 2012 Elsevier Inc. All rights reserved.

  19. Kisspeptin Stimulates Growth Hormone Release by Utilizing Neuropeptide Y Pathways and Is Dependent on the Presence of Ghrelin in the Ewe.

    Science.gov (United States)

    Foradori, Chad D; Whitlock, Brian K; Daniel, Jay A; Zimmerman, Arthur D; Jones, Melaney A; Read, Casey C; Steele, Barbara P; Smith, Jeremy T; Clarke, Iain J; Elsasser, Theodore H; Keisler, Duane H; Sartin, James L

    2017-10-01

    Although kisspeptin is the primary stimulator of gonadotropin-releasing hormone secretion and therefore the hypothalamic-pituitary-gonadal axis, recent findings suggest kisspeptin can also regulate additional neuroendocrine processes including release of growth hormone (GH). Here we show that central delivery of kisspeptin causes a robust rise in plasma GH in fasted but not fed sheep. Kisspeptin-induced GH secretion was similar in animals fasted for 24 hours and those fasted for 72 hours, suggesting that the factors involved in kisspeptin-induced GH secretion are responsive to loss of food availability and not the result of severe negative energy balance. Pretreatment with the neuropeptide Y (NPY) Y1 receptor antagonist, BIBO 3304, blocked the effects of kisspeptin-induced GH release, implicating NPY as an intermediary. Kisspeptin treatment induced c-Fos in NPY and GH-releasing hormone (GHRH) cells of the arcuate nucleus. The same kisspeptin treatment resulted in a reduction in c-Fos in somatostatin (SS) cells in the periventricular nucleus. Finally, blockade of systemic ghrelin release or antagonism of the ghrelin receptor eliminated or reduced the ability of kisspeptin to induce GH release, suggesting the presence of ghrelin is required for kisspeptin-induced GH release in fasted animals. Our findings support the hypothesis that during short-term fasting, systemic ghrelin concentrations and NPY expression in the arcuate nucleus rise. This permits kisspeptin activation of NPY cells. In turn, NPY stimulates GHRH cells and inhibits SS cells, resulting in GH release. We propose a mechanism by which kisspeptin conveys reproductive and hormone status onto the somatotropic axis, resulting in alterations in GH release. Copyright © 2017 Endocrine Society.

  20. Exposure of zebrafish embryos/larvae to TDCPP alters concentrations of thyroid hormones and transcriptions of genes involved in the hypothalamic-pituitary-thyroid axis.

    Science.gov (United States)

    Wang, Qiangwei; Liang, Kang; Liu, Jingfu; Yang, Lihua; Guo, Yongyong; Liu, Chunsheng; Zhou, Bingsheng

    2013-01-15

    Tris(1,3-dichloro-2-propyl) phosphate (TDCPP) has been frequently detected in the environment and in various biota, including fish, and has been implicated in disruption of the thyroid endocrine system. In the present study, zebrafish (Danio rerio) embryos were exposed to different concentrations of TDCPP (10, 50, 100, 300 and 600 μg/L) from 2 h post-fertilization (hpf) to 144 hpf. Developmental endpoints, and whole-body concentrations of thyroid hormones and transcriptional profiles of genes involved in the hypothalamic-pituitary-thyroid (HPT) axis were examined. Exposure to TDCPP caused a dose-dependent developmental toxicity, including decreased body weight, reduced hatching, survival and heartbeat rates, and increased malformation (spinal curvature). Treatment with the positive control chemical 3,3',5-triiodo-l-thyronine (T3) significantly decreased whole-body thyroxin (T4) concentrations, increased whole-body T3 concentrations, and upregulated mRNA expression involved in the HPT axis as a compensatory mechanism. These results suggested that the HPT axis in 144-hpf zebrafish larvae was responsive to chemical exposure and could be used to evaluate the effects of chemicals on the thyroid endocrine system. TDCPP exposure significantly decreased whole-body T4 concentrations and increased whole-body T3 concentrations, indicating thyroid endocrine disruption. The upregulation of genes related to thyroid hormone metabolism (dio1 and ugt1ab) might be responsible for decreased T4 concentrations. Treatment with TDCPP also significantly increased transcription of genes involved in thyroid hormone synthesis (tshβ, slc5a5 and tg) and thyroid development (hhex, nkx2.1 and pax8) as a compensatory mechanism for decreased T4 concentrations. Taken together, these results suggest that TDCPP alters the transcription of genes involved in the HPT axis and changes whole-body concentrations of thyroid hormones in zebrafish embryos/larvae, thus causing an endocrine disruption of the

  1. Escin suppresses migration and invasion involving the alteration of CXCL16/CXCR6 axis in human gastric adenocarcinoma AGS cells.

    Science.gov (United States)

    Lee, Hyun Sook; Hong, Ji Eun; Kim, Eun Ji; Kim, Sun Hyo

    2014-01-01

    Escin, a natural mixture of triterpene saponins isolated from horse chestnut, has been reported to possess anticancer activity in many human cancer cells. However, the effect of escin on the metastasis has not been studied. The present study examined the effect of escin on the migration and invasion of AGS human gastric cancer cells. To examine the effects of escin on metastatic capacities of gastric cancer cells, AGS cells were cultured in the presence of 0-4 μmol/L escin. Escin inhibited cell migration and invasion in AGS cells. However, escin did not affect the viability of these cells at these concentrations. The chemokine receptor and its ligands play an important role in cancer metastasis. Escin decreased the production of soluble C-X-C motif chemokine (CXCL)16 but increased the expression of trans-membranous CXCL16. The expression of C-X-C chemokine receptor (CXCR)6 was not affected by escin treatment. Exogenous CXCL16 reversed escin-induced migration inhibition. In addition, escin inhibited the phosphorylation of focal adhesion kinase and Akt. These results demonstrate that escin inhibited the migration and invasion of AGS cells, which is associated with altered CXCL16/CXCR6 axis. These findings suggest that escin has potential as an antimetastatic agent in gastric cancer.

  2. Β-catenin-dependent control of positional information along the AP body axis in planarians involves a teashirt family member.

    Science.gov (United States)

    Reuter, Hanna; März, Martin; Vogg, Matthias C; Eccles, David; Grífol-Boldú, Laura; Wehner, Daniel; Owlarn, Suthira; Adell, Teresa; Weidinger, Gilbert; Bartscherer, Kerstin

    2015-01-13

    Wnt/β-catenin signaling regulates tissue homeostasis and regeneration in metazoans. In planarians-flatworms with high regenerative potential-Wnt ligands are thought to control tissue polarity by shaping a β-catenin activity gradient along the anterior-posterior axis, yet the downstream mechanisms are poorly understood. We performed an RNA sequencing (RNA-seq)-based screen and identified hundreds of β-catenin-dependent transcripts, of which several were expressed in muscle tissue and stem cells in a graded fashion. In particular, a teashirt (tsh) ortholog was induced in a β-catenin-dependent manner during regeneration in planarians and zebrafish, and RNAi resulted in two-headed planarians. Strikingly, intact planarians depleted of tsh induced anterior markers and slowly transformed their tail into a head, reminiscent of β-catenin RNAi phenotypes. Given that β-catenin RNAi enhanced the formation of muscle cells expressing anterior determinants in tail regions, our study suggests that this pathway controls tissue polarity through regulating the identity of differentiating cells during homeostasis and regeneration. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  3. β-Catenin-Dependent Control of Positional Information along the AP Body Axis in Planarians Involves a Teashirt Family Member

    Directory of Open Access Journals (Sweden)

    Hanna Reuter

    2015-01-01

    Full Text Available Wnt/β-catenin signaling regulates tissue homeostasis and regeneration in metazoans. In planarians—flatworms with high regenerative potential—Wnt ligands are thought to control tissue polarity by shaping a β-catenin activity gradient along the anterior-posterior axis, yet the downstream mechanisms are poorly understood. We performed an RNA sequencing (RNA-seq-based screen and identified hundreds of β-catenin-dependent transcripts, of which several were expressed in muscle tissue and stem cells in a graded fashion. In particular, a teashirt (tsh ortholog was induced in a β-catenin-dependent manner during regeneration in planarians and zebrafish, and RNAi resulted in two-headed planarians. Strikingly, intact planarians depleted of tsh induced anterior markers and slowly transformed their tail into a head, reminiscent of β-catenin RNAi phenotypes. Given that β-catenin RNAi enhanced the formation of muscle cells expressing anterior determinants in tail regions, our study suggests that this pathway controls tissue polarity through regulating the identity of differentiating cells during homeostasis and regeneration.

  4. Environmental and genetic contributors to salivary testosterone levels in infants

    Directory of Open Access Journals (Sweden)

    Kai eXia

    2014-10-01

    Full Text Available Transient activation of the hypothalamic-pituitary-gonadal axis in early infancy plays an important role in male genital development and sexual differentiation of the brain, but factors contributing to individual variation in testosterone levels during this period are poorly understood. We measured salivary testosterone levels in 222 infants (119 males, 103 females, 108 singletons, 114 twins between 2.70 and 4.80 months of age. We tested 16 major demographic and medical history variables for effects on inter-individual variation in salivary testosterone. Using the subset of twins, we estimated genetic and environmental contributions to salivary testosterone levels. Finally, we tested single nucleotide polymorphisms (SNPs within ± 5kb of genes involved in testosterone synthesis, transport, signaling, and metabolism for associations with salivary testosterone using univariate tests and random forest (RF analysis. We report an association between 5 minute APGAR scores and salivary testosterone levels in males. Twin modelling indicated that individual variability in testosterone levels was primarily explained by environmental factors. Regarding genetic variation, univariate tests did not reveal any variants significantly associated with salivary testosterone after adjusting for false discovery rate. The top hit in males was rs10923844, a SNP of unknown function located downstream of HSD3B1 and HSD3B2. The top hits in females were two SNPs located upstream of ESR1 (rs3407085 and rs2295190. RF analysis, which reflects joint and conditional effects of multiple variants, indicated that genes involved in regulation of reproductive function, particularly LHCGR, are related to salivary testosterone levels in male infants, as are genes involved in cholesterol production, transport, and removal, while genes involved in estrogen signaling are related to salivary testosterone levels in female infants.

  5. Revisiting the wandering womb: Oxytocin in endometriosis and bipolar disorder.

    Science.gov (United States)

    Dinsdale, Natalie L; Crespi, Bernard J

    2017-11-01

    Hippocrates attributed women's high emotionality - hysteria - to a 'wandering womb'. Although hysteria diagnoses were abandoned along with the notion that displaced wombs cause emotional disturbance, recent research suggests that elevated levels of oxytocin occur in both bipolar disorder and endometriosis, a gynecological condition involving migration of endometrial tissue beyond the uterus. We propose and evaluate the hypothesis that elevated oxytocinergic system activity jointly contributes to bipolar disorder and endometriosis. First, we provide relevant background on endometriosis and bipolar disorder, and then we examine evidence for comorbidity between these conditions. We next: (1) review oxytocin's associations with personality traits, especially extraversion and openness, and how they overlap with bipolar spectrum traits; (2) describe evidence for higher oxytocinergic activity in both endometriosis and bipolar disorder; (3) examine altered hypothalamic-pituitary-gonadal axis functioning in both conditions; (4) describe data showing that medications that treat one condition can improve symptoms of the other; (5) discuss fitness-related impacts of endometriosis and bipolar disorder; and (6) review a pair of conditions, polycystic ovary syndrome and autism, that show evidence of involving reduced oxytocinergic activity, in direct contrast to endometriosis and bipolar disorder. Considered together, the bipolar spectrum and endometriosis appear to involve dysregulated high extremes of normally adaptive pleiotropy in the female oxytocin system, whereby elevated levels of oxytocinergic activity coordinate outgoing sociality with heightened fertility, apparently characterizing, overall, a faster life history. These findings should prompt a re-examination of how mind-body interactions, and the pleiotropic endocrine systems that underlie them, contribute to health and disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Role of leptin in female reproduction.

    Science.gov (United States)

    Pérez-Pérez, Antonio; Sánchez-Jiménez, Flora; Maymó, Julieta; Dueñas, José L; Varone, Cecilia; Sánchez-Margalet, Víctor

    2015-01-01

    Reproductive function is dependent on energy resources. The role of weight, body composition, fat distribution and the effect of diet have been largely investigated in experimental female animals as well as in women. Any alteration in diet and/or weight may induce abnormalities in timing of sexual maturation and fertility. However, the cellular mechanisms involved in the fine coordination of energy balance and reproduction are largely unknown. The brain and hypothalamic structures receive endocrine and/or metabolic signals providing information on the nutritional status and the degree of fat stores. Adipose tissue acts both as a store of energy and as an active endocrine organ, secreting a large number of biologically important molecules termed adipokines. Adipokines have been shown to be involved in regulation of the reproductive functions. The first adipokine described was leptin. Extensive research over the last 10 years has shown that leptin is not only an adipose tissue-derived messenger of the amount of energy stores to the brain, but also a crucial hormone/cytokine for a number of diverse physiological processes, such as inflammation, angiogenesis, hematopoiesis, immune function, and most importantly, reproduction. Leptin plays an integral role in the normal physiology of the reproductive system with complex interactions at all levels of the hypothalamic-pituitary gonadal (HPG) axis. In addition, leptin is also produced by placenta, where it plays an important autocrine function. Observational studies have demonstrated that states of leptin excess, deficiency, or resistance can be associated with abnormal reproductive function. This review focuses on the leptin action in female reproduction.

  7. Endocrine-Manifestations of Cirrhosis and Liver Disease

    Directory of Open Access Journals (Sweden)

    M Khalili

    2014-04-01

    Full Text Available The liver is involved in the synthesis and metabolism of many kinds of hormones, various abnormalities hormone levels are found in advanced liver disease. For example the liver is, extremely sensitive to changes in insulin or glucagon levels. The liver is the primary organ of iron storage is frequently involved, diabetes is common in patients with iron overload and may be seen in cirrhosis. Chronic infection with HCV is associated with insulin resistance. Thyroid disease often accompanies chronic hepatitis C infection .Anti thyroid autoantibodies are also found in chronic HCV infection. Nonalcoholic liver disease (NAFLDas a most common cause of chronic liver disease in western world ,as well accompanied by Type 2 diabetes and hyperlipidemia. Hypopituitarism and hypothyroidism also have been in NAFLD.The patients with NAFLD and Hypopituitarism may be susceptible to central obesity, dyslipidemia and insulin resistance leading to disease progression. Hepatic cirrhosis as the end stage of chronic liver disease is also associated with hypogonadism and signs of feminization. The peripheral metabolism of steroids is altered in many of hypogonadism, low testosterone level decreased libido, infertility, reduced secondary sex hair and gynecomastia, reduced spermatogenesis and peritubular fibrosis are found in men with cirrhosis .The normal function of the hypothalamic-pituitary gonadal axis is affected in liver disease. In cirrhotic patients the estrogen/androgen ratio is usually increased, the level of testosterone and dihydroepiandosteron are reduced while the estradiol level are normal or slightly elevated, these alterations are dependent on the severity of the liver disease.Succsesfull orthotropic liver transplantation  leads to improvement of the sex hormone disturbances. The pathogenesis of gynecomastia is due to the loss of equilibrium between estrogen and androgen caused by a feminizing state but it is due to increased estrogen precursor in

  8. A review of reproductive toxicity of microcystins

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Liang, E-mail: chan91@yeah.net [Donghu Experimental Station of Lake Ecosystems, State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072 (China); University of Chinese Academy of Sciences, Beijing 100049 (China); Chen, Jun, E-mail: chenjun@ihb.ac.cn [Donghu Experimental Station of Lake Ecosystems, State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072 (China); Zhang, Xuezhen, E-mail: xuezhen@mail.hzau.edu.cn [College of Fisheries, Huazhong Agricultural University, Freshwater Aquaculture Collaborative Innovation Center of Hubei Province, Wuhan 430070 (China); Xie, Ping, E-mail: xieping@ihb.ac.cn [Donghu Experimental Station of Lake Ecosystems, State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072 (China)

    2016-01-15

    Highlights: • Reproductive toxicity of MCs on mammals, fishes, amphibians, and birds is reviewed. • PP1/2A inhibition and oxidative stress are important toxic mechanisms of MCs. • Reproductive toxicity of MCs may be closely related to endocrine-disrupting effects. • The trans-generational toxicity of microcystins is a matter of concern. • Data concerning female reproductive and sex-specific effects of MCs are lacking. - Abstract: Animal studies provide strong evidence of positive associations between microcystins (MCs) exposure and reproductive toxicity, representing a threat to human reproductive health and the biodiversity of wild life. This paper reviews current knowledge of the reproductive toxicity of MCs, with regard to mammals, fishes, amphibians, and birds, mostly in males. Toxicity of MCs is primarily governed by the inhibition of protein phosphatases 1 and 2A (PP1 and PP2A) and disturbance of cellular phosphorylation balance. MCs exposure is related to excessive production of reactive oxygen species (ROS) and oxidative stress, leading to cytoskeleton disruption, mitochondria dysfunction, endoplasmic reticulum (ER) stress, and DNA damage. MCs induce cell apoptosis mediated by the mitochondrial and ROS and ER pathways. Through PP1/2A inhibition and oxidative stress, MCs lead to differential expression/activity of transcriptional factors and proteins involved in the pathways of cellular differentiation, proliferation, and tumor promotion. MC-induced DNA damage is also involved in carcinogenicity. Apart from a direct effect on testes and ovaries, MCs indirectly affect sex hormones by damaging the hypothalamic-pituitary-gonad (HPG) axis and liver. Parental exposure to MCs may result in hepatotoxicity and neurotoxicity of offspring. We also summarize the current research gaps which should be addressed by further studies.

  9. Early postnatal treatment with clomipramine induces female sexual behavior and estrous cycle impairment.

    Science.gov (United States)

    Molina-Jiménez, Tania; Limón-Morales, Ofelia; Bonilla-Jaime, Herlinda

    2018-03-01

    Administration of clomipramine (CMI), a tricyclic antidepressant, in early stages of development in rats, is considered an animal model for the study of depression. This pharmacological manipulation has induced behavioral and physiological alterations, i.e., less pleasure-seeking behaviors, despair, hyperactivity, cognitive dysfunction, alterations in neurotransmitter systems and in HPA axis. These abnormalities in adult male rats are similar to the symptoms observed in major depressive disorders. One of the main pleasure-seeking behaviors affected in male rats treated with CMI is sexual behavior. However, to date, no effects of early postnatal CMI treatment have been reported on female reproductive cyclicity and sexual behavior. Therefore, we explored CMI administration in early life (8-21 PN) on the estrous cycle and sexual behavior of adult female rats. Compared to the rats in the early postnatal saline treatment (CTRL group), the CMI rats had fewer estrous cycles, fewer days in the estrous stage, and longer cycles during a 20-day period of vaginal cytology analysis. On the behavioral test, the CMI rats displayed fewer proceptive behaviors (hopping, darting) and had lower lordosis quotients. Also, they usually failed to display lordosis and only rarely manifested marginal or normal lordosis. In contrast, the CTRL rats tended to display normal lordosis. These results suggest that early postnatal CMI treatment caused long-term disruptions of the estrous cycle and female sexual behavior, perhaps by alteration in the hypothalamic-pituitary-gonadal (HPG) axes and in neuronal circuits involved in the regulation of the performance and motivational of sexual behavior as the noradrenergic and serotonergic systems. Copyright © 2018 Elsevier Inc. All rights reserved.

  10. The complex genetic basis of congenital hypogonadotropic hypogonadism.

    Science.gov (United States)

    Vezzoli, Valeria; Duminuco, Paolo; Bassi, Ivan; Guizzardi, Fabiana; Persani, Luca; Bonomi, Marco

    2016-06-01

    Congenital hypogonadotropic hypogonadism (CHH) is a rare disease characterized by delayed/absent puberty and infertility due to an inadequate secretion or action of gonadotrophin-releasing hormone (GnRH), with an otherwise structurally and functionally normal hypothalamic-pituitary-gonadal (HPG) axis. CHH is genetically heterogeneous but, due to the infertility of affected individuals, most frequently emerges in a sporadic form, though numerous familial cases have also been registered. In around 50-60% of cases, CHH is associated with a variety of non-reproductive abnormalities, most commonly anosmia/hyposmia, which defines Kallmann Syndrome (KS) by its presence. Broadly-speaking, genetic defects that directly impact on hypothalamic secretion, regulation, or action of GnRH result in a pure neuroendocrine phenotype, normosmic CHH (nCHH), whereas genetic defects that impact of embryonic migration of GnRH neurons to the hypothalamus most commonly result in KS, though nCHH can also arise. Hence, the description of several pedigrees, comprising subjects exhibiting KS and others with nCHH. Although more than 24 genes have been described to be involved in CHH, molecular variants of these do not presently explain more than 35-45% of reported cases. Therefore, numerous other unidentified genes (or conceivably, epigenetic mechanisms) remain to be described to fully understand the pathogenesis of CHH, explaining the emergent idea that CHH is a complex genetic disease characterized by variable expressivity and penetrance. This review summarizes the current state of knowledge on the complex genetic basis of congenital hypogonadotropic hypogonadism and aims to be accessible to both researchers and clinicians.

  11. Biology of insulin-like factor 3 in human reproduction.

    Science.gov (United States)

    Ivell, Richard; Anand-Ivell, Ravinder

    2009-01-01

    BACKGROUND Insulin-like factor 3 (INSL3) is a neohormone that has evolved to address specific mammalian traits, in particular, the first phase of testicular descent towards the scrotum during mid-gestation. METHODS A thorough literature search was made in PubMed using the terms INSL3, as well as the older synonyms RLF and Ley-IL. RESULTS INSL3 is a major secretory product of the testicular Leydig cells in the fetus and in adult men, and in rodent models, reduction in fetal INSL3 expression is an early marker of the testicular dysgenesis syndrome. In women, it is produced in lower amounts by ovarian theca and luteal cells, and circulating levels are increased in women with polycystic ovarian syndrome. During pregnancy, there is evidence for an interaction regulating the feto-placental unit. The presence of INSL3 in amniocentesis samples taken at 12-14 weeks gestation is absolutely specific for male gender, and levels are predictive of subsequent pre-eclampsia and/or birthweight. INSL3 is also involved in adult traits, such as spermatogenesis and bone metabolism. In adult men, INSL3 is constitutively expressed and secreted into the bloodstream at a constant level, reflecting the number and/or functional capacity of the Leydig cells. In complete contrast, testosterone is highly variable within individuals, is acutely responsive to fluctuations in the hypothalamic-pituitary-gonadal axis and appears to have marginal diagnostic value. INSL3 declines consistently with age in adult men. CONCLUSIONS INSL3 promises to become an important new diagnostic tool to characterize those men with late-onset hypogonadism and to add clinical diagnostic value at amniocentesis.

  12. Sex differences in the physiology of eating

    Science.gov (United States)

    Asarian, Lori

    2013-01-01

    Hypothalamic-pituitary-gonadal (HPG) axis function fundamentally affects the physiology of eating. We review sex differences in the physiological and pathophysiological controls of amounts eaten in rats, mice, monkeys, and humans. These controls result from interactions among genetic effects, organizational effects of reproductive hormones (i.e., permanent early developmental effects), and activational effects of these hormones (i.e., effects dependent on hormone levels). Male-female sex differences in the physiology of eating involve both organizational and activational effects of androgens and estrogens. An activational effect of estrogens decreases eating 1) during the periovulatory period of the ovarian cycle in rats, mice, monkeys, and women and 2) tonically between puberty and reproductive senescence or ovariectomy in rats and monkeys, sometimes in mice, and possibly in women. Estrogens acting on estrogen receptor-α (ERα) in the caudal medial nucleus of the solitary tract appear to mediate these effects in rats. Androgens, prolactin, and other reproductive hormones also affect eating in rats. Sex differences in eating are mediated by alterations in orosensory capacity and hedonics, gastric mechanoreception, ghrelin, CCK, glucagon-like peptide-1 (GLP-1), glucagon, insulin, amylin, apolipoprotein A-IV, fatty-acid oxidation, and leptin. The control of eating by central neurochemical signaling via serotonin, MSH, neuropeptide Y, Agouti-related peptide (AgRP), melanin-concentrating hormone, and dopamine is modulated by HPG function. Finally, sex differences in the physiology of eating may contribute to human obesity, anorexia nervosa, and binge eating. The variety and physiological importance of what has been learned so far warrant intensifying basic, translational, and clinical research on sex differences in eating. PMID:23904103

  13. Testosterone production during puberty in two 46,XY patients with disorders of sex development and novel NR5A1 (SF-1) mutations.

    Science.gov (United States)

    Tantawy, Sally; Lin, Lin; Akkurt, Ilker; Borck, Guntram; Klingmüller, Dietrich; Hauffa, Berthold P; Krude, Heiko; Biebermann, Heike; Achermann, John C; Köhler, Birgit

    2012-07-01

    Steroidogenic factor 1 (SF-1, NR5A1) is a key transcriptional regulator of many genes involved in the hypothalamic-pituitary-gonadal axis and mutations in NR5A1 can result in 46,XY disorders of sex development (DSD). Patients with this condition typically present with ambiguous genitalia, partial gonadal dysgenesis, and absent/rudimentary Müllerian structures. In these cases, testosterone is usually low in early infancy, indicating significantly impaired androgen synthesis. Further, Sertoli cell dysfunction is seen (low inhibin B, anti-Müllerian hormone). However, gonadal function at puberty in patients with NR5A1 mutations is unknown. Clinical assessment, endocrine evaluation, and genetic analysis were performed in one female and one male with 46,XY DSD who showed spontaneous virilization during puberty. The female patient presented at adolescence with clitoral hypertrophy, whereas the male patient presented at birth with severe hypospadias and entered puberty spontaneously. Molecular analysis of NR5A1 was performed followed by in vitro functional analysis of the two novel mutations detected. Testosterone levels were normal during puberty in both patients. Analysis of NR5A1 revealed two novel heterozygous missense mutations in the ligand-binding domain of SF-1 (patient 1: p.L376F; patient 2: p.G328V). The mutant proteins showed reduced transactivation of the CYP11A promoter in vitro. Patients with 46,XY DSD and NR5A1 mutations can produce sufficient testosterone for spontaneous virilization during puberty. Phenotypic females (46,XY) with NR5A1 mutations can present with clitoromegaly at puberty, a phenotype similar to other partial defects of androgen synthesis or action. Testosterone production in 46,XY males with NR5A1 mutations can be sufficient for virilization at puberty. As progressive gonadal dysgenesis is likely, gonadal function should be monitored in adolescence and adulthood, and early sperm cryopreservation considered in male patients if possible.

  14. Mucuna pruriens and its major constituent L-DOPA recover spermatogenic loss by combating ROS, loss of mitochondrial membrane potential and apoptosis.

    Directory of Open Access Journals (Sweden)

    Akhand Pratap Singh

    Full Text Available BACKGROUND: The Ayurvedic medicinal system claims Mucuna pruriens (MP to possess pro-male fertility, aphrodisiac and adaptogenic properties. Some scientific evidence also supports its pro-male fertility properties; however, the mechanism of its action is not yet clear. The present study aimed at demonstrating spermatogenic restorative efficacy of MP and its major constituent L-DOPA (LD, and finding the possible mechanism of action thereof in a rat model. METHODOLOGY/FINDINGS: Ethinyl estradiol (EE was administered at a rate of 3 mg/kg body weight (BW/day for a period of 14 days to generate a rat model with compromised spermatogenesis. MP and LD were administered in two separate groups of these animals starting 15(th day for a period of 56 days, and the results were compared with an auto-recovery (AR group. Sperm count and motility, testis histo-architecture, level of reactive oxygen species (ROS, mitochondrial membrane potential (MMP, apoptosis, peripheral hormone levels and testicular germ cell populations were analysed, in all experimental groups. We observed efficient and quick recovery of spermatogenesis in MP and LD groups in comparison to the auto-recovery group. The treatment regulated ROS level, apoptosis, and mitochondrial membrane potential (MMP, recovered the hypothalamic-pituitary-gonadal axis and the number of testicular germ cells, ultimately leading to increased sperm count and motility. CONCLUSION/SIGNIFICANCE: M. pruriens efficiently recovers the spermatogenic loss induced due to EE administration. The recovery is mediated by reduction in ROS level, restoration of MMP, regulation of apoptosis and eventual increase in the number of germ cells and regulation of apoptosis. The present study simplified the complexity of mechanism involved and provided meaningful insights into MP/LD mediated correction of spermatogenic impairment caused by estrogens exposure. This is the first study demonstrating that L-DOPA largely accounts for pro

  15. Polycystic ovary syndrome in adolescent girls.

    Science.gov (United States)

    Baldauff, Natalie Hecht; Witchel, Selma Feldman

    2017-02-01

    Polycystic ovary syndrome (PCOS) is a common heterogeneous disorder that appears to have its origins during the peripubertal years. The diagnostic conundrum is that the typical clinical features, irregular menses and acne, occur during normal female puberty. Understanding the physiologic origins and molecular basis of the dysregulated hypothalamic-pituitary-gonadal axis in PCOS is fundamental to interrupting the distinctive vicious cycle of hyperandrogenism and chronic anovulation. Newer ultrasound technology with better spatial resolution has generated controversy regarding the optimal imaging criteria to define polycystic ovary morphology. Using such equipment, the Androgen Excess PCOS Society Task Force Report recommends a threshold of at least 25 follicles per ovary as the definition of polycystic ovary morphology. The implementation and results of genome-wide association studies has opened a new window into the pathogenesis of PCOS. Recent genome-wide association studies have identified several loci near genes involved in gonadotropin secretion, ovarian function, and metabolism. Despite the impediments posed by phenotypic and genetic heterogeneity among women with PCOS, investigation into one locus, the DENND1A gene, is providing insight into the ovarian steroidogenesis. Anti-Mullerian hormone (AMH) has long been recognized to play a major role in the ovarian dysfunction. Recent animal data implicate AMH in the neuroendocrine dysregulation by demonstrating AMH-stimulated increased gonadotropin releasing hormone and luteinizing hormone secretion. PCOS is a common complex multifaceted disorder associated with genetic and environmental influences affecting steroidogenesis, steroid metabolism, neuroendocrine function, insulin sensitivity, pancreatic β cell function, and alternative adaptations to energy excess. Current research into the genetics and pathophysiology is reviewed. The difficulties inherent in diagnosing PCOS in adolescent girls are discussed.

  16. Oxytocin Intranasal Administration Affects Neural Networks Upstream of GNRH Neurons.

    Science.gov (United States)

    Salehi, Mohammad Saied; Khazali, Homayoun; Mahmoudi, Fariba; Janahmadi, Mahyar

    2017-08-01

    The last decade has witnessed a surge in studies on the clinical applications of intranasal oxytocin as a method of enhancing social interaction. However, the molecular and cellular mechanisms underlying its function are not completely understood. Since oxytocin is involved in the regulation of hypothalamic-pituitary-gonadal axis by affecting the gonadotropin-releasing hormone (GNRH) system, the present study addressed whether intranasal application of oxytocin has a role in affecting GNRH expression in the male rat hypothalamus. In addition, we assessed expression of two excitatory (kisspeptin and neurokinin B) and two inhibitory (dynorphin and RFamide-related peptide-3) neuropeptides upstream of GNRH neurons as a possible route to relay oxytocin information. Here, adult male rats received 20, 40, or 80 μg oxytocin intranasally once a day for 10 consecutive days, and then, the posterior (PH) and anterior hypothalamus (AH) dissected for evaluation of target genes. Using qRT-PCR, we found that oxytocin treatment increased Gnrh mRNA levels in both the PH and AH. In addition, oxytocin at its highest dose increased kisspeptin expression in the AH by around 400%, whereas treatments, dose dependently decreased kisspeptin mRNA in the PH. The expression of neurokinin B was increased from the basal levels following the intervention. Furthermore, although intranasal-applied oxytocin decreased hypothalamic RFamide-related peptide-3 mRNA level, the dynorphin mRNA was not affected. These observations are consistent with the hypothesis that applications of intranasal oxytocin can affect the GNRH system.

  17. Sex differences in the physiology of eating.

    Science.gov (United States)

    Asarian, Lori; Geary, Nori

    2013-12-01

    Hypothalamic-pituitary-gonadal (HPG) axis function fundamentally affects the physiology of eating. We review sex differences in the physiological and pathophysiological controls of amounts eaten in rats, mice, monkeys, and humans. These controls result from interactions among genetic effects, organizational effects of reproductive hormones (i.e., permanent early developmental effects), and activational effects of these hormones (i.e., effects dependent on hormone levels). Male-female sex differences in the physiology of eating involve both organizational and activational effects of androgens and estrogens. An activational effect of estrogens decreases eating 1) during the periovulatory period of the ovarian cycle in rats, mice, monkeys, and women and 2) tonically between puberty and reproductive senescence or ovariectomy in rats and monkeys, sometimes in mice, and possibly in women. Estrogens acting on estrogen receptor-α (ERα) in the caudal medial nucleus of the solitary tract appear to mediate these effects in rats. Androgens, prolactin, and other reproductive hormones also affect eating in rats. Sex differences in eating are mediated by alterations in orosensory capacity and hedonics, gastric mechanoreception, ghrelin, CCK, glucagon-like peptide-1 (GLP-1), glucagon, insulin, amylin, apolipoprotein A-IV, fatty-acid oxidation, and leptin. The control of eating by central neurochemical signaling via serotonin, MSH, neuropeptide Y, Agouti-related peptide (AgRP), melanin-concentrating hormone, and dopamine is modulated by HPG function. Finally, sex differences in the physiology of eating may contribute to human obesity, anorexia nervosa, and binge eating. The variety and physiological importance of what has been learned so far warrant intensifying basic, translational, and clinical research on sex differences in eating.

  18. Stromal Derived Factor-1/CXCR4 Axis Involved in Bone Marrow Mesenchymal Stem Cells Recruitment to Injured Liver

    Directory of Open Access Journals (Sweden)

    Kuai Xiao Ling

    2016-01-01

    Full Text Available The molecular mechanism of bone marrow mesenchymal stromal stem cells (BMSCs mobilization and migration to the liver was poorly understood. Stromal cell-derived factor-1 (SDF-1 participates in BMSCs homing and migration into injury organs. We try to investigate the role of SDF-1 signaling in BMSCs migration towards injured liver. The expression of CXCR4 in BMSCs at mRNA level and protein level was confirmed by RT-PCR, flow cytometry, and immunocytochemistry. The SDF-1 or liver lysates induced BMSCs migration was detected by transwell inserts. CXCR4 antagonist, AMD3100, and anti-CXCR4 antibody were used to inhibit the migration. The Sprague-Dawley rat liver injury model was established by intraperitoneal injection of thioacetamide. The concentration of SDF-1 increased as modeling time extended, which was determined by ELISA method. The Dir-labeled BMSCs were injected into the liver of the rats through portal vein. The cell migration in the liver was tracked by in vivo imaging system and the fluorescent intensity was measured. In vivo, BMSCs migrated into injured liver which was partially blocked by AMD3100 or anti-CXCR4 antibody. Taken together, the results demonstrated that the migration of BMSCs was regulated by SDF-1/CXCR4 signaling which involved in BMSCs recruitment to injured liver.

  19. Involvement of the CXCR7/CXCR4/CXCL12 axis in the malignant progression of human neuroblastoma.

    Directory of Open Access Journals (Sweden)

    Julie Liberman

    Full Text Available Neuroblastoma (NB is a typical childhood and heterogeneous neoplasm for which efficient targeted therapies for high-risk tumors are not yet identified. The chemokine CXCL12, and its receptors CXCR4 and CXCR7 have been involved in tumor progression and dissemination. While CXCR4 expression is associated to undifferentiated tumors and poor prognosis, the role of CXCR7, the recently identified second CXCL12 receptor, has not yet been elucidated in NB. In this report, CXCR7 and CXCL12 expressions were evaluated using a tissue micro-array including 156 primary and 56 metastatic NB tissues. CXCL12 was found to be highly associated to NB vascular and stromal structures. In contrast to CXCR4, CXCR7 expression was low in undifferentiated tumors, while its expression was stronger in matured tissues and specifically associated to differentiated neural tumor cells. As determined by RT-PCR, CXCR7 expression was mainly detected in N-and S-type NB cell lines, and was slightly induced upon NB cell differentiation in vitro. The relative roles of the two CXCL12 receptors were further assessed by overexpressing CXCR7 or CXCR4 receptor alone, or in combination, in the IGR-NB8 and the SH-SY5Y NB cell lines. In vitro functional analyses indicated that, in response to their common ligand, both receptors induced activation of ERK1/2 cascade, but not Akt pathway. CXCR7 strongly reduced in vitro growth, in contrast to CXCR4, and impaired CXCR4/CXCL12-mediated chemotaxis. Subcutaneous implantation of CXCR7-expressing NB cells showed that CXCR7 also significantly reduced in vivo growth. Moreover, CXCR7 affected CXCR4-mediated orthotopic growth in a CXCL12-producing environment. In such model, CXCR7, in association with CXCR4, did not induce NB cell metastatic dissemination. In conclusion, the CXCR7 and CXCR4 receptors revealed specific expression patterns and distinct functional roles in NB. Our data suggest that CXCR7 elicits anti-tumorigenic functions, and may act as a

  20. The hypoxanthine-xanthine oxidase axis is not involved in the initial phase of clinical transplantation-related ischemia-reperfusion injury

    NARCIS (Netherlands)

    Wijermars, Leonie G. M.; Bakker, Jaap A.; de Vries, Dorottya K.; van Noorden, Cornelis J. F.; Bierau, Jörgen; Kostidis, Sarantos; Mayboroda, Oleg A.; Tsikas, Dimitrios; Schaapherder, Alexander F.; Lindeman, Jan H. N.

    2017-01-01

    The hypoxanthine-xanthine oxidase (XO) axis is considered to be a key driver of transplantation-related ischemia-reperfusion (I/R) injury. Whereas interference with this axis effectively quenches I/R injury in preclinical models, there is limited efficacy of XO inhibitors in clinical trials. In this

  1. Sex Differences in Circadian Timing Systems: Implications for Disease

    Science.gov (United States)

    Bailey, Matthew; Silver, Rae

    2014-01-01

    Virtually every eukaryotic cell has an endogenous circadian clock and a biological sex. These cell-based clocks have been conceptualized as oscillators whose phase can be reset by internal signals such as hormones, and external cues such as light. The present review highlights the inter-relationship between circadian clocks and sex differences. In mammals, the suprachiasmatic nucleus (SCN) serves as a master clock synchronizing the phase of clocks throughout the body. Gonadal steroid receptors are expressed in almost every site that receives direct SCN input. Here we review sex differences in the circadian timing system in the hypothalamic-pituitary-gonadal axis (HPG), the hypothalamicadrenal-pituitary (HPA) axis, and sleep-arousal systems. We also point to ways in which disruption of circadian rhythms within these systems differs in the sexes and is associated with dysfunction and disease. Understanding sex differentiated circadian timing systems can lead to improved treatment strategies for these conditions. PMID:24287074

  2. Central Circadian Control of Female Reproductive Function

    Directory of Open Access Journals (Sweden)

    Brooke H Miller

    2014-01-01

    Full Text Available Over the past two decades, it has become clear just how much of our physiology is under the control of the suprachiasmatic nucleus (SCN and the cell-intrinsic molecular clock that ticks with a periodicity of approximately 24 hours. The SCN prepares our digestive system for meals, our adrenal axis for the stress of waking up in the morning, and the genes expressed in our muscles when we prepare to exercise, Long before molecular studies of genes such as Clock, Bmal1, and the Per homologs were possible, it was obvious that female reproductive function was under strict circadian control at every level of the hypothalamic-pituitary-gonadal (HPG axis, and in the establishment and successful maintenance of pregnancy. This review highlights our current understanding of the role that the SCN plays in regulating female reproductive physiology, with a special emphasis on the advances made possible through the use of circadian mutant mice.

  3. Hepatitis C virus-induced natural killer cell proliferation involves monocyte-derived cells and the OX40/OX40L axis.

    Science.gov (United States)

    Pollmann, Julia; Götz, Jana-Julia; Rupp, Daniel; Strauss, Otto; Granzin, Markus; Grünvogel, Oliver; Mutz, Pascal; Kramer, Catharina; Lasitschka, Felix; Lohmann, Volker; Björkström, Niklas K; Thimme, Robert; Bartenschlager, Ralf; Cerwenka, Adelheid

    2018-03-01

    Natural killer (NK) cells are found at increased frequencies in patients with hepatitis C virus (HCV). NK cell activation has been shown to correlate with HCV clearance and to predict a favourable treatment response. The aim of our study was to dissect mechanisms leading to NK cell activation and proliferation in response to HCV. NK cell phenotype, proliferation, and function were assessed after the 6-day co-culture of human peripheral blood mononuclear cells with either HCV replicon-containing HuH6 hepatoblastoma cells or HCV-infected HuH7.5 cells. The results obtained were confirmed by immunohistochemistry of liver biopsies from patients with HCV and from HCV-negative controls. In HCV-containing co-cultures, a higher frequency of NK cells upregulated the expression of the high-affinity IL-2 receptor chain CD25, proliferated more rapidly, and produced higher amounts of interferon γ compared with NK cells from control co-cultures. This NK cell activation was dependent on IL-2, cell-cell contact-mediated signals, and HCV replicon-exposed monocytes. The tumour necrosis factor-receptor superfamily member OX40 was induced on the activated CD25 ± NK cell subset and this induction was abrogated by the depletion of CD14 + monocytes. Moreover, OX40L was upregulated on CD14 ± monocyte-derived cells co-cultured with HCV-containing cells and also observed in liver biopsies from patients with HCV. Importantly, blocking of the OX40/OX40L interaction abolished both NK cell activation and proliferation. Our results uncover a previously unappreciated cell-cell contact-mediated mechanism of NK cell activation and proliferation in response to HCV, mediated by monocyte-derived cells and the OX40/OX40L axis. These results reveal a novel mode of crosstalk between innate immune cells during viral infection. Using a cell-culture model of hepatitis C virus (HCV) infection, our study revealed that natural killer (NK) cells become activated and proliferate when they are co-cultured with

  4. Menstrual cycle, beta-endorphins, and pain sensitivity in premenstrual dysphoric disorder.

    Science.gov (United States)

    Straneva, Patricia A; Maixner, William; Light, Kathleen C; Pedersen, Cort A; Costello, Nancy L; Girdler, Susan S

    2002-07-01

    This study examined pain sensitivity and pain modularity mechanisms (e.g., beta-endorphin levels, blood pressure) in women with premenstrual dysphoric disorder (PMDD; n = 27) and healthy controls (n = 27) during the follicular and luteal phases of the menstrual cycle. Physiological measures were taken during rest and ischemic pain testing. In both cycle phases, PMDD women (a) displayed lower resting cortisol and beta-endorphin levels and (b) exhibited shorter pain threshold and tolerance times and greater pain unpleasantness ratings during pain. PMDD women also reported greater pain unpleasantness and intensity and had lower beta-endorphin levels in their luteal phase and tended to display higher blood pressure levels at rest and during pain testing. Results suggest that endogenous opioids may be pathophysiologically relevant to PMDD and that the hypothalamic-pituitary-gonadal axis may modulate pain sensitivity in PMDD.

  5. Peroxisome proliferator-activated receptor gamma signaling in human sperm physiology.

    Science.gov (United States)

    Liu, Li-Li; Xian, Hua; Cao, Jing-Chen; Zhang, Chong; Zhang, Yong-Hui; Chen, Miao-Miao; Qian, Yi; Jiang, Ming

    2015-01-01

    Peroxisome proliferator-activated receptor gamma (PPARγ) is a member of the PPARs, which are transcription factors of the steroid receptor superfamily. PPARγ acts as an important molecule for regulating energy homeostasis, modulates the hypothalamic-pituitary-gonadal (HPG) axis, and is reciprocally regulated by HPG. In the human, PPARγ protein is highly expressed in ejaculated spermatozoa, implying a possible role of PPARγ signaling in regulating sperm energy dissipation. PPARγ protein is also expressed in Sertoli cells and germ cells (spermatocytes). Its activation can be induced during capacitation and the acrosome reaction. This mini-review will focus on how PPARγ signaling may affect fertility and sperm quality and the potential reversibility of these adverse effects.

  6. Clomiphene citrate therapy for male infertility.

    Science.gov (United States)

    Allag, I S; Alexander, N J

    1979-11-01

    We have summarized 697 reported cases of the use of clomiphene citrate for the improvement of semen quality. Basal levels of gonadotropins are useful criteria for the differential diagnosis of hypo- and hypergonadotropic hypogonadism. Patients with an intact hypothalamic-pituitary-gonadal axis are most likely to respond to clomiphene citrate. Twenty-five mg. per day, administered in a cyclic fashion for a period of six to nine months, caused the greatest improvement. A higher dose (50 mg. per day) may be effective in men who do not respond to 25 mg. During the course of therapy gonadotropin levels and semen samples should be analyzed periodically. This drug is not currently approved for use in men; the incidence of side effects, particularly with long-term treatment, is unknown.

  7. Mouse models of altered gonadotrophin action: insight into male reproductive disorders.

    Science.gov (United States)

    Jonas, Kim C; Oduwole, Olayiwola O; Peltoketo, Hellevi; Rulli, Susana B; Huhtaniemi, Ilpo T

    2014-10-01

    The advent of technologies to genetically manipulate the mouse genome has revolutionised research approaches, providing a unique platform to study the causality of reproductive disorders in vivo. With the relative ease of generating genetically modified (GM) mouse models, the last two decades have yielded multiple loss-of-function and gain-of-function mutation mouse models to explore the role of gonadotrophins and their receptors in reproductive pathologies. This work has provided key insights into the molecular mechanisms underlying reproductive disorders with altered gonadotrophin action, revealing the fundamental roles of these pituitary hormones and their receptors in the hypothalamic-pituitary-gonadal axis. This review will describe GM mouse models of gonadotrophins and their receptors with enhanced or diminished actions, specifically focusing on the male. We will discuss the mechanistic insights gained from these models into male reproductive disorders, and the relationship and understanding provided into male human reproductive disorders originating from altered gonadotrophin action. © 2014 Society for Reproduction and Fertility.

  8. GnRH, anosmia and hypogonadotropic hypogonadism--where are we?

    Science.gov (United States)

    Forni, Paolo E; Wray, Susan

    2015-01-01

    Gonadotropin releasing hormone (GnRH) neurons originate the nasal placode and migrate into the brain during prenatal development. Once within the brain, these cells become integral components of the hypothalamic-pituitary-gonadal axis, essential for reproductive function. Disruption of this system causes hypogonadotropic hypogonadism (HH). HH associated with anosmia is clinically defined as Kallman syndrome (KS). Recent work examining the developing nasal region has shed new light on cellular composition, cell interactions and molecular cues responsible for the development of this system in different species. This review discusses some developmental aspects, animal models and current advancements in our understanding of pathologies affecting GnRH. In addition we discuss how development of neural crest derivatives such as the glia of the olfactory system and craniofacial structures control GnRH development and reproductive function. Published by Elsevier Inc.

  9. Ghrelin in Female and Male Reproduction

    Directory of Open Access Journals (Sweden)

    Joëlle Dupont

    2010-01-01

    Full Text Available Ghrelin and one of its functional receptors, GHS-R1a (Growth Hormone Secretagogue Receptor 1a, were firstly studied about 15 years. Ghrelin is a multifunctional peptide hormone that affects several biological functions including food intake, glucose release, cell proliferation… Ghrelin and GHS-R1a are expressed in key cells of both male and female reproductive organs in several species including fishes, birds, and mammals suggesting a well-conserved signal through the evolution and a role in the control of fertility. Ghrelin could be a component of the complex series of nutrient sensors such as adipokines, and nuclear receptors, which regulate reproduction in function of the energy stores. The objective of this paper was to report the available information about the ghrelin system and its role at the level of the hypothalamic-pituitary-gonadal axis in both sexes.

  10. Micropenis

    Directory of Open Access Journals (Sweden)

    Jeremy Wiygul

    2011-01-01

    Full Text Available Micropenis is part of a larger group of conditions broadly known as inconspicuous penis; however, it is fundamentally different from the other diagnoses in this group, such as webbed penis and buried penis, in that the underlying problem is the size of the penis itself, not with the surrounding and overlying skin. This condition is usually the result of a defect in the hypothalamic-pituitary-gonadal axis, although iatrogenic causes are identified infrequently. Management revolves around testosterone (direct administration or encouraging the patient's body to make its own, and long-term results with respect to increase in penile length are promising. Reconstructive surgery is based on the use of a vascular pedicle free flap and is reserved for patients who fail to respond to hormonal treatment. Although substantial long-term data are lacking, adult patients with micropenis appear to report dissatisfaction with penile appearance, but the majority appear to have adequate sexual function.

  11. Effect of a postnatal high-fat diet exposure on puberty onset, estrous cycle regularity, and kisspeptin expression in female rats

    DEFF Research Database (Denmark)

    Lie, Maria Elena Klibo; Overgaard, Agnete; Mikkelsen, Jens D

    2013-01-01

    Kisspeptin, encoded by Kiss1, plays a key role in pubertal maturation and reproduction as a positive upstream regulator of the hypothalamic-pituitary-gonadal (HPG) axis. To examine the role of high-fat diet (HFD) on puberty onset, estrous cycle regularity, and kisspeptin expression, female rats...... were exposed to HFD in distinct postnatal periods. Three groups of rats were exposed to HFD containing 60% energy from fat during the pre-weaning period (postnatal day (PND) 1-16, HFD PND 1-16), post-weaning period (HFD PND 21-34), or during both periods (HFD PND 1-34). Puberty onset, evaluated...... by vaginal opening, was monitored on days 30-34. Leptin, estradiol (E2), Kiss1 mRNA levels, and number of kisspeptin-immunoreactive cells in the anteroventral periventricular nucleus (AVPV) and arcuate nucleus (ARC) were measured at day 34. Body weight increased only in rats exposed to HFD during post...

  12. Gonadotropin levels in urine during early postnatal period in small for gestational age preterm male infants with fetal growth restriction.

    Science.gov (United States)

    Nagai, S; Kawai, M; Myowa-Yamakoshi, M; Morimoto, T; Matsukura, T; Heike, T

    2017-07-01

    The objective of this study was to estimate gonadotropin concentrations in small for gestational age (SGA) male infants with the reactivation of the hypothalamic-pituitary-gonadal axis during the first few months of life that is important for genital development. We prospectively examined 15 SGA and 15 appropriate for gestational age (AGA) preterm male infants between 2013 and 2014 at Kyoto University Hospital. Gonadotropin concentrations (luteinizing hormone (LH) and follicle-stimulating hormone (FSH)) were measured in serial urine samples from the postnatal days 7 to 168 and compared between SGA and AGA infants using the Mann-Whitney test. A longitudinal analysis showed that SGA infants had higher LH and lower FSH concentrations (P=0.004 and P=0.006, respectively) than AGA infants. Male infants who are SGA at birth because of fetal growth restriction have gonadotropin secretion abnormalities in the first few months of life.

  13. A missense mutation in MKRN3 in a Danish girl with central precocious puberty and her brother with early puberty

    DEFF Research Database (Denmark)

    Känsäkoski, Johanna; Raivio, Taneli; Juul, Anders

    2015-01-01

    BACKGROUND: Idiopathic central precocious puberty (ICPP) results from the premature reactivation of the hypothalamic-pituitary-gonadal axis leading to development of secondary sexual characteristics prior to 8 y in girls or 9 y in boys. Since the initial discovery of mutations in the maternally...... imprinted MKRN3 gene in 2013, several case reports have described mutations in this gene in ICPP patients from different populations, highlighting the importance of MKRN3 as a regulator of pubertal onset. METHODS: We screened 29 Danish girls with ICPP for mutations in MKRN3. Expression of MKRN3 in human...... hypothalamic complementary DNA (cDNA) was investigated by PCR. RESULTS: One paternally inherited rare variant, c.1034G>A (p.Arg345His), was identified in one girl with ICPP and in her brother with early puberty. The variant is predicted to be deleterious by three different in silico prediction programs...

  14. Inhibin B in the assessment of seminiferous tubular function

    DEFF Research Database (Denmark)

    Andersson, A M

    2000-01-01

    to the activity of the hypothalamic-pituitary-gonadal hormone axis. During childhood, the basal serum inhibin B level is a direct marker of the presence and function of testicular tissue that has proved useful in the diagnosis of patients with cryptorchidism or ambiguous genitalia. In adult men, the inhibin B......Inhibin B is a testicular hormone that regulates follicle-stimulating hormone secretion in a negative feedback loop. In males, the serum level of inhibin B is detectable throughout life, with a prominent change in the first year of life and during puberty, reflecting the testicular response...... level is closely related to spermatogenesis. Measurements of serum inhibin B may provide valuable clues for the differential diagnosis of male infertility. A further exploration of the relationship between inhibin B, Sertoli cell function and spermatogenesis will improve the usefulness of inhibin B...

  15. Neuroendocrine dysfunction in Sjogren's syndrome.

    Science.gov (United States)

    Tzioufas, Athanasios G; Tsonis, John; Moutsopoulos, Haralampos M

    2008-01-01

    Interactions among the immune, nervous and endocrine systems, which are mediated by hormones, neuropeptides, neurotransmitters, cytokines and their receptors, appear to play an important role in modulating host susceptibility and resistance to inflammatory disease. The neuroendocrine system has two main components: the central and the peripheral. The central compartment is located in the locus ceruleus, the brainstem centers of the autonomic system and the paraventricular nucleus; the peripheral mainly consists of the sympathetic/adrenomedullary system, the hypothalamic-pituitary-adrenal axis (HPA), the hypothalamic-pituitary-gonadal (HPG) axis, and the neuroendocrine tissue located in several organs throughout the body. Hormones and neuropeptides may influence the activities of lymphoid organs and cells via endocrine and local autocrine/paracrine pathways or alter the function of different cell types in target organs. Recent studies highlighted alterations of the neuroendocrine system in systemic autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus and Sjogren's syndrome (SS). SS, a prototype autoimmune disorder, has a wide clinical spectrum, extending from organ involvement (autoimmune exocrinopathy) to systemic disease and B cell lymphoma. In SS, several functions of the neuroendocrine system are impaired. First, the HPA axis appears to be disturbed, since significantly lower basal ACTH and cortisol levels were found in patients with SS and were associated with a blunted pituitary and adrenal response to ovine corticotropin-releasing factor compared to normal controls. Second, HPG axis is also involved, since lack of estrogens is associated with human disease and the development of autoimmune exocrinopathy in several experimental models. Finally, exocrine glands are enriched with neuroendocrine-related molecules, adjacent to local autoimmune lesions. Certain clinical manifestations of the disease, including the sicca manifestations

  16. Determinants of testosterone levels in human male obesity.

    Science.gov (United States)

    Bekaert, Marlies; Van Nieuwenhove, Yves; Calders, Patrick; Cuvelier, Claude A; Batens, Arsène-Hélène; Kaufman, Jean-Marc; Ouwens, D Margriet; Ruige, Johannes B

    2015-09-01

    Testosterone (T) levels are decreased in obese men, but the underlying causes are incompletely understood. Our objective was to explore the relation between low (free) T levels and male obesity, by evaluating metabolic parameters, subcutaneous adipose tissue (SAT) aromatase expression, and parameters of the hypothalamic-pituitary-gonadal axis. We recruited 57 morbidly obese men [33 had type 2 diabetes (DM2)] and 25 normal-weight men undergoing abdominal surgery. Fourteen obese men also attended a follow-up, 2 years after gastric bypass surgery (GBS). Circulating T levels were quantified by LC-MS/MS, whereas free T levels were measured using serum equilibrium dialysis and sex hormone-binding globulin, luteinizing hormone, and follicle-stimulating hormone by immunoassay. SAT biopsies were used to determine adipocyte cell size and aromatase expression by real-time PCR. Total and free T levels were decreased in obese males versus controls, with a further decrease in obese men with DM2 versus obese men without DM2. There were no differences in aromatase expression among the study groups, and sex steroids did not correlate with aromatase expression. Pearson analysis revealed an inverse association between (free) T and SAT cell size, triglycerides, and HOMA-IR. Multivariate analysis confirmed the inverse association between (free) T and SAT cell size (β = -0.321, P = 0.037 and β = -0.441, P = 0.011, respectively), independent of age, triglycerides, HOMA-IR, obesity, or diabetes. T levels were normalized 2 years after GBS. These data suggest that SAT cell size rather than SAT aromatase expression or parameters of the hypothalamic-pituitary-gonadal axis is related to low T in male obesity, which points to adipose cell size-related metabolic changes as a major trigger in decreased T levels.

  17. The depressive-like behaviors of chronic unpredictable mild stress-treated mice ameliorated by Tibetan medicine Zuotai: involvement in the hypothalamic–pituitary–adrenal (HPA axis pathway

    Directory of Open Access Journals (Sweden)

    Zhao J

    2018-01-01

    Full Text Available Jing Zhao,1,2 Cuiying Niu,1–3 Jianv Wang,1,3 Hongxia Yang,1,2 Yuzhi Du,1,2 Lixin Wei,1,2 Cen Li1,2 1Pharmacology and Safety Evaluation Key Laboratory of Tibetan Medicine in Qinghai Province, Northwest Institute of Plateau Biology, 2Key Laboratory of Tibetan Medicine Research, Chinese Academy of Sciences, Xining, Qinghai, 3University of Chinese Academy of Sciences, Beijing, People’s Republic of China Background: Zuotai, a famous Tibetan medicinal mixture containing metacinnabar, is traditionally used for the purpose of tranquilizing minds and soothing nerves. However, it still lacks substantial experimental data for it to be approved for use.Aim: This study was designed to assess the effects of Zuotai on depressive-like symptoms in a chronic unpredictable mild stress (CUMS mouse model, and to explore its potential mechanism, particularly the hypothalamic–pituitary–adrenal (HPA axis pathway.Materials and methods: First, Kunming mice were exposed to the CUMS procedure and simultaneously administered Zuotai or imipramine (positive control by gavage continuously for 6 weeks. Then, depressive-like behaviors of mice in each group were tested with the sucrose preference test, forced swimming test, tail suspension test, and open field test. Meanwhile, the three key neuroendocrine hormones (corticotropin releasing hormone, adrenocorticotropic hormone and corticosterone in HPA axis pathway, and the level of the emotion-related monoamine neurotransmitters (5-hydroxytryptamine and norepinephrine were measured using enzyme-linked immunosorbent assay. Furthermore, total mercury in the hypothalamus and hippocampus were determined using an automatic, direct mercury analyzer.Results: Zuotai or imipramine significantly increased the body weight and the sucrose preference ratio in sucrose preference test, and dramatically improved motor activity in forced swimming test, tail suspension test, and open field test in CUMS mice. Zuotai or imipramine remarkably

  18. The involvement of the hypothalamopituitary-adrenocortical axis in stress physiology and its significance in the assessment of animal welfare in cattle

    Directory of Open Access Journals (Sweden)

    Emma J. Brown

    2017-04-01

    Full Text Available The intensification of cattle production has raised concern for animal welfare due to the stress that is associated with farming practices. The welfare of an animal is determined by the animal’s ability to cope with or adapt to its continuously changing environment and the biological cost that is associated with this adaptation and maintenance. Stressors arise from various psychological, physiological and physical aspects of farming practices due to management and human–cattle interactions. Measuring the activity of the hypothalamopituitary-adrenocortical (HPA axis with plasma cortisol levels is a useful method for determining the effects of stress on animals as it is stimulated at the onset of a perceived stress. The activation of the HPA axis affects various target tissues or systems and can result in suppression of the immune system, increased susceptibility to disease and adverse effects on reproductive success in prenatal and neonatal calves. Although some levels of stress associated with farming practices are unavoidable, improvements in farming methods need to be implemented in order to maintain or increase the efficiency of cattle production in a way that does not compromise the welfare of the animal.

  19. miR-24-3p/FGFR3 Signaling as a Novel Axis Is Involved in Epithelial-Mesenchymal Transition and Regulates Lung Adenocarcinoma Progression

    Directory of Open Access Journals (Sweden)

    Pengyu Jing

    2018-01-01

    Full Text Available Our previous studies showed that Fibroblast growth factor receptor 3 (FGFR3 contributed to cell growth in lung cancer. However, the correlation between FGFR3 and tumor progression, coupled with the underlying mechanisms, are not fully understood. The clinical significance of FGFR3 was determined in two cohorts of clinical samples (n=22, n=78. A panel of biochemical assays and functional experiments was utilized to elucidate the underlying mechanisms and effects of FGFR3 and miR-24-3p on lung adenocarcinoma progression. Upregulated FGFR3 expression indicated an adverse prognosis for lung adenocarcinoma individuals and promoted metastatic potential of lung adenocarcinoma cells. Owing to the direct regulation towards FGFR3, miR-24-3p could interfere with the potential of proliferation, migration, and invasion in lung adenocarcinoma, following variations of EMT-related protein expression. As a significant marker of EMT, E-cadherin was negatively correlated with FGFR3, of which ectopic overexpression could neutralize the antitumour effects of miR-24-3p and reverse its regulatory effects on EMT markers. Taken together, these findings define a novel insight into the miR-24-3p/FGFR3 signaling axis in regulating lung adenocarcinoma progression and suggest that targeting the miR-24-3p/FGFR3 axis could be an effective and efficient way to prevent tumor progression.

  20. The involvement of the hypothalamopituitary-adrenocortical axis in stress physiology and its significance in the assessment of animal welfare in cattle.

    Science.gov (United States)

    Brown, Emma J; Vosloo, Andre

    2017-04-28

    The intensification of cattle production has raised concern for animal welfare due to the stress that is associated with farming practices. The welfare of an animal is determined by the animal's ability to cope with or adapt to its continuously changing environment and the biological cost that is associated with this adaptation and maintenance. Stressors arise from various psychological, physiological and physical aspects of farming practices due to management and human-cattle interactions. Measuring the activity of the hypothalamopituitary-adrenocortical (HPA) axis with plasma cortisol levels is a useful method for determining the effects of stress on animals as it is stimulated at the onset of a perceived stress. The activation of the HPA axis affects various target tissues or systems and can result in suppression of the immune system, increased susceptibility to disease and adverse effects on reproductive success in prenatal and neonatal calves. Although some levels of stress associated with farming practices are unavoidable, improvements in farming methods need to be implemented in order to maintain or increase the efficiency of cattle production in a way that does not compromise the welfare of the animal.

  1. Axis Spectrometer

    International Nuclear Information System (INIS)

    Park, Sungil

    2006-01-01

    The Cold Neutron Research Facility (CNRF) project carried out by Korea Atomic Energy Research Institute (KAERI) is an effort to bring cold neutron instrumentation to Korea's only large scale research reactor, HANARO, located in Daejeon. As part of the CNRF project, a cold neutron triple-axis spectrometer (Cold-TAS) is being developed along with other five: 40 m long and 12 m long small angle neutron scattering instruments (40m-SANS and 12m-SANS), disk-chopper time-of-flight spectrometer (DC-ToF), Bio- Reflectometer (Bio-REF) and the reflectometer with vertical sample geometry (REF-V). For those cold neutron instruments, the performance of an individual instrument depends not only on its design but also on the guide that feeds cold neutrons to the instrument. Therefore, the quality of the neutron flux at an instrument position has to be checked with the specification of the instrument. As for the Cold-TAS, since the instrument requires a tall beam and a high flux of short wavelength neutrons, it was tentatively decided that it would use the cold guide 4 (CG4). The detailed specification of the guide is listed. Checking the neutron flux of the guide at the instrument position is the obvious next step

  2. Protective Macroautophagy Is Involved in Vitamin E Succinate Effects on Human Gastric Carcinoma Cell Line SGC-7901 by Inhibiting mTOR Axis Phosphorylation.

    Directory of Open Access Journals (Sweden)

    Liying Hou

    Full Text Available Vitamin E succinate (VES, a potential cancer therapeutic agent, potently induces apoptosis and inhibits the growth of various cancer cells. Autophagy has been supposed to promote cancer cell survival or trigger cell death, depending on particular cancer types and tumor microenvironments. The role of autophagy in the growth suppressive effect of VES on gastric cancer cell is basically unknown. We aimed to determine whether and how autophagy affected the VES-induced inhibition of SGC-7901 human gastric carcinoma cell growth. SGC-7901 cells were treated with VES or pre-treated with autophagy inhibitor, chloroquine (CQ and 3-methyladenine (3-MA. Electron microscopy, fluorescence microscopy and Western blot were used to study whether VES induced autophagy reaction in SGC-7901 cells. Western blot evaluated the activities of the mammalian target of rapamycin (mTOR axis. Then we used 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT and flow cytometry to detect the level of cell viability and apoptosis. Collectively, our data indeed strongly support our hypothesis that VES treatment produced cytological variations that depict autophagy, increased the amount of intracellular green fluorescent protein-microtubule associated protein 1 light chain 3 (GFP-LC3 punctate fluorescence and the number of autophagic vacuoles. It altered the expression of endogenous autophagy marker LC3. VES activated the suppression of mTOR through inhibiting upstream regulators p38 MAPK and Akt. mTOR suppression consequently inhibited the activation of mTOR downstream targets p70S6K and 4E-BP-1. The activation of the upstream mTOR inhibitor AMPK had been up-regulated by VES. The results showed that pre-treatment SGC-7901 with autophagy inhibitors before VES treatment could increase the capacity of VES to reduce cell viability and to provoke apoptosis. In conclusion, VES-induced autophagy participates in SGC-7901 cell protection by inhibiting mTOR axis

  3. The GTPase activating Rap/RanGAP domain-like 1 gene is associated with chicken reproductive traits.

    Directory of Open Access Journals (Sweden)

    Xu Shen

    Full Text Available BACKGROUND: Abundant evidence indicates that chicken reproduction is strictly regulated by the hypothalamic-pituitary-gonad (HPG axis, and the genes included in the HPG axis have been studied extensively. However, the question remains as to whether any other genes outside of the HPG system are involved in regulating chicken reproduction. The present study was aimed to identify, on a genome-wide level, novel genes associated with chicken reproductive traits. METHODOLOGY/PRINCIPAL FINDING: Suppressive subtractive hybridization (SSH, genome-wide association study (GWAS, and gene-centric GWAS were used to identify novel genes underlying chicken reproduction. Single marker-trait association analysis with a large population and allelic frequency spectrum analysis were used to confirm the effects of candidate genes. Using two full-sib Ningdu Sanhuang (NDH chickens, GARNL1 was identified as a candidate gene involved in chicken broodiness by SSH analysis. Its expression levels in the hypothalamus and pituitary were significantly higher in brooding chickens than in non-brooding chickens. GWAS analysis with a NDH two tail sample showed that 2802 SNPs were significantly associated with egg number at 300 d of age (EN300. Among the 2802 SNPs, 2 SNPs composed a block overlapping the GARNL1 gene. The gene-centric GWAS analysis with another two tail sample of NDH showed that GARNL1 was strongly associated with EN300 and age at first egg (AFE. Single marker-trait association analysis in 1301 female NDH chickens confirmed that variation in this gene was related to EN300 and AFE. The allelic frequency spectrum of the SNP rs15700989 among 5 different populations supported the above associations. Western blotting, RT-PCR, and qPCR were used to analyze alternative splicing of the GARNL1 gene. RT-PCR detected 5 transcripts and revealed that the transcript, which has a 141 bp insertion, was expressed in a tissue-specific manner. CONCLUSIONS/SIGNIFICANCE: Our findings

  4. Mango polyphenolics reduce inflammation in intestinal colitis-involvement of the miR-126/PI3K/AKT/mTOR axis in vitro and in vivo.

    Science.gov (United States)

    Kim, Hyemee; Banerjee, Nivedita; Barnes, Ryan C; Pfent, Catherine M; Talcott, Stephen T; Dashwood, Roderick H; Mertens-Talcott, Susanne U

    2017-01-01

    This study sought to elucidate the mechanisms underlying the anti-inflammatory effect of mango (Mangifera Indica L.) polyphenolics containing gallic acid and gallotanins, and the role of the miR-126/PI3K/AKT/mTOR signaling axis in vitro and in vivo. Polyphenolics extracted from mango (var. Keitt) were investigated in lipopolysaccharide (LPS)-treated CCD-18Co cells. Rats received either a beverage with mango polyphenolics or a control beverage, and were exposed to three cycles of 3% dextran sodium sulfate (DSS) followed by a 2-wk recovery period. The mango extract (10 mg GAE/L) suppressed the protein expression of NF-κB, p-NF-κB, PI3K (p85β), HIF-1α, p70S6K1, and RPS6 in LPS-treated CCD-18Co cells. LPS reduced miR-126 expression, whereas, the mango extract induced miR-126 expression in a dose-dependent manner. The relationship between miR-126 and its target, PI3K (p85β), was confirmed by treating cells with miR-126 antagomiR where mango polyphenols reversed the effects of the antagomiR. In vivo, mango beverage protected against DSS-induced colonic inflammation (47%, P = 0.05) and decreased the Ki-67 labeling index in the central and basal regions compared to the control. Mango beverage significantly attenuated the expression of pro-inflammatory cytokines such as TNF-α, IL-1β, and iNOS at the mRNA and protein level. Moreover, the expression of PI3K, AKT, and mTOR was reduced, whereas, miR-126 was upregulated by the mango treatment. These results suggest that mango polyphenols attenuated inflammatory response by modulating the PI3K/AKT/mTOR pathway at least in part through upregulation of miRNA-126 expression both in vitro and in vivo; thus, mango polyphenolics might be relevant as preventive agents in ulcerative colitis. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  5. Mango Polyphenolics Reduce Inflammation in Intestinal Colitis—Involvement of the miR-126/PI3K/AKT/mTOR Axis In Vitro and In Vivo

    Science.gov (United States)

    Kim, Hyemee; Banerjee, Nivedita; Barnes, Ryan C.; Pfent, Catherine M.; Talcott, Stephen T.; Dashwood, Roderick H.; Mertens-Talcott, Susanne U.

    2016-01-01

    This study sought to elucidate the mechanisms underlying the anti-inflammatory effect of mango (Mangifera Indica L.) polyphenolics containing gallic acid and gallotanins, and the role of the miR-126/PI3K/AKT/mTOR signaling axis in vitro and in vivo. Polyphenolics extracted from mango (var. Keitt) were investigated in lipopolysaccharide (LPS)-treated CCD-18Co cells. Rats received either a beverage with mango polyphenolics or a control beverage, and were exposed to three cycles of 3% dextran sodium sulfate (DSS) followed by a 2-wk recovery period. The mango extract (10 mg GAE/L) suppressed the protein expression of NF-κB, p-NF-κB, PI3K (p85β), HIF-1α, p70S6K1, and RPS6 in LPS-treated CCD-18Co cells. LPS reduced miR-126 expression, whereas, the mango extract induced miR-126 expression in a dose-dependent manner. The relationship between miR-126 and its target, PI3K (p85β), was confirmed by treating cells with miR-126 antagomiR where mango polyphenols reversed the effects of the antagomiR. In vivo, mango beverage protected against DSS-induced colonic inflammation (47%, P = 0.05) and decreased the Ki-67 labeling index in the central and basal regions compared to the control. Mango beverage significantly attenuated the expression of pro-inflammatory cytokines such as TNF-α, IL-1β, and iNOS at the mRNA and protein level. Moreover, the expression of PI3K, AKT, and mTOR was reduced, whereas, miR-126 was upregulated by the mango treatment. These results suggest that mango polyphenols attenuated inflammatory response by modulating the PI3K/AKT/mTOR pathway at least in part through upregulation of miRNA-126 expression both in vitro and in vivo; thus, mango polyphenolics might be relevant as preventive agents in ulcerative colitis. PMID:27061150

  6. Communication requested: Boar semen transport through the uterus and possible consequences for insemination.

    Science.gov (United States)

    Rath, D; Knorr, C; Taylor, U

    2016-01-01

    several species, an ovulation-inducing factor exists in seminal plasma, first identified as ß-nerve growth factor in camelid semen, indicating another pathway that influences the hypothalamic-pituitary-gonadal axis. In summary, low-dose inseminations may not necessarily require semen deposition deep into the uterine horn, as binding inhibitors can circumvent the binding of sperm to the uterine wall. However, subsequent immune-relevant events that control ovulation and prepare the uterine milieu for the developing embryo should be taken into account. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Downregulation of Smurf2, a tumor-suppressive ubiquitin ligase, in triple-negative breast cancers: Involvement of the RB-microRNA axis

    International Nuclear Information System (INIS)

    Liu, Xianpeng; Gu, Xin; Sun, Limin; Flowers, Ashley B; Rademaker, Alfred W; Zhou, Yiran; Kiyokawa, Hiroaki

    2014-01-01

    The HECT family ubiquitin ligase Smurf2 regulates cell polarity, migration, division, differentiation and death, by targeting diverse substrates that are critical for receptor signaling, cytoskeleton, chromatin remodeling and transcription. Recent studies suggest that Smurf2 functions as a tumor suppressor in mice. However, no inactivating mutation of SMURF2 has been reported in human, and information about Smurf2 expression in human cancer remains limited or complicated. Here we demonstrate that Smurf2 expression is downregulated in human breast cancer tissues, especially of the triple-negative subtype, and address the mechanism of Smurf2 downregulation in triple-negative breast cancer cells. Human breast cancer tissues (47 samples expressing estrogen receptor (ER) and 43 samples with triple-negative status) were examined by immunohistochemistry for the expression of Smurf2. Ten widely-studied human breast cancer cell lines were examined for the expression of Smurf2. Furthermore, microRNA-mediated regulation of Smurf2 was investigated in triple-negative cancer cell lines. Immunohistochemical analysis showed that benign mammary epithelial cells expressed high levels of Smurf2, so did cells in ductal carcinomas in situ. In contrast, invasive ductal carcinomas showed focal or diffuse decrease in Smurf2 expression, which was observed more frequently in triple-negative tumors than in ER-positive tumors. Consistently, human triple-negative breast cancer cell lines such as BT549, MDA-MB-436, DU-4475 and MDA-MB-468 cells showed significantly lower expression of Smurf2 protein, compared to ER + or HER2+ cell lines. Studies using quantitative PCR and specific microRNA inhibitors indicated that increased expression of miR-15a, miR-15b, miR-16 and miR-128 was involved in Smurf2 downregulation in those triple-negative cancer cell lines, which have mutations in the retinoblastoma (RB) gene. Forced expression of RB increased levels of Smurf2 protein with concomitant decreases in

  8. Analysis of the gene coding for steroidogenic factor 1 (SF1, NR5A1) in a cohort of 50 Egyptian patients with 46,XY disorders of sex development.

    Science.gov (United States)

    Tantawy, Sally; Mazen, Inas; Soliman, Hala; Anwar, Ghada; Atef, Abeer; El-Gammal, Mona; El-Kotoury, Ahmed; Mekkawy, Mona; Torky, Ahmad; Rudolf, Agnes; Schrumpf, Pamela; Grüters, Annette; Krude, Heiko; Dumargne, Marie-Charlotte; Astudillo, Rebekka; Bashamboo, Anu; Biebermann, Heike; Köhler, Birgit

    2014-05-01

    Steroidogenic factor 1 (SF1, NR5A1) is a key transcriptional regulator of genes involved in the hypothalamic-pituitary-gonadal axis. Recently, SF1 mutations were found to be a frequent cause of 46,XY disorders of sex development (DSD) in humans. We investigate the frequency of NR5A1 mutations in an Egyptian cohort of XY DSD. Clinical assessment, endocrine evaluation and genetic analysis of 50 Egyptian XY DSD patients (without adrenal insufficiency) with a wide phenotypic spectrum. Molecular analysis of NR5A1 gene by direct sequencing followed by in vitro functional analysis of the two novel missense mutations detected. Three novel heterozygous mutations of the coding region in patients with hypospadias were detected. p.Glu121AlafsX25 results in severely truncated protein, p.Arg62Cys lies in DNA-binding zinc finger, whereas p.Ala154Thr lies in the hinge region of SF1 protein. Transactivation assays using reporter constructs carrying promoters of anti-Müllerian hormone (AMH), CYP11A1 and TESCO core enhancer of Sox9 showed that p.Ala154Thr and p.Arg62Cys mutations result in aberrant biological activity of NR5A1. A total of 17 patients (34%) harboured the p.Gly146Ala polymorphism. We identified two novel NR5A1 mutations showing impaired function in 23 Egyptian XY DSD patients with hypospadias (8.5%). This is the first study searching for NR5A1 mutations in oriental patients from the Middle East and Arab region with XY DSD and no adrenal insufficiency, revealing a frequency similar to that in European patients (6.5-15%). We recommend screening of NR5A1 in patients with hypospadias and gonadal dysgenesis. Yearly follow-ups of gonadal function and early cryoconservation of sperms should be performed in XY DSD patients with NR5A1 mutations given the risk of future fertility problems due to early gonadal failure.

  9. LH and testosterone production are more sensitive to the suppressive effects of food deprivation in prenatally undernourished male rats.

    Science.gov (United States)

    Iwasa, Takeshi; Matsuzaki, Toshiya; Tungalagsuvd, Altankhuu; Munkhzaya, Munkhsaikhan; Kuwahara, Akira; Yasui, Toshiyuki; Irahara, Minoru

    2015-06-01

    Although prenatal undernutrition affects the development of metabolic, physiological, and reproductive functions, it remains unclear whether it also affects physiological responses to undernutrition in adulthood. Therefore, in this study we examined whether prenatal undernutrition alters the sensitivity of the hypothalamic-pituitary-gonadal (HPG) axis to fasting in adult male rats. The offspring of ad libitum fed dams (control) and ∼50% food-restricted (during the late gestational period) dams (IUGR) were sub-divided into ad libitum fed (fed) and 48 h food deprivation (FD) groups at 10 weeks of age. In each group, the serum levels of luteinizing hormone (LH), testosterone, and leptin and the hypothalamic mRNA expression levels of gonadotropin-releasing hormone (GnRH) regulatory factors were measured. The serum LH and testosterone levels of the IUGR-fed rats were significantly or tend to be higher than those of the control-fed rats, respectively. The serum LH levels of the IUGR-FD rats were lower than those of the IUGR-fed rats. Similarly, the serum testosterone levels of the IUGR-FD rats tended to be lower than those of the IUGR-fed rats. On the other hand, the serum LH and testosterone levels of the control-fed and control-FD rats did not differ. The serum leptin levels of the IUGR fed rats were higher than those of the control-fed rats. The serum leptin levels of the control-FD and IUGR-FD rats were lower than those of the control-fed and IUGR-fed rats, respectively. The hypothalamic neuropeptide Y (NPY) mRNA levels of the IUGR-FD rats were higher than those of the IUGR-fed rats. Similarly, hypothalamic NPY mRNA levels of control-FD rats were higher than those of the control-fed rats. The hypothalamic kisspeptin, kisspeptin receptor, RFamide-related peptide, GPR147, and OBRb mRNA levels of control fed rats did not differ between control-fed and IUGR-fed rats. Their mRNA levels of the fed and FD rats did not differ in the control or IUGR groups. These results

  10. Pomegranate polyphenolics reduce inflammation and ulceration in intestinal colitis-involvement of the miR-145/p70S6K1/HIF1α axis in vivo and in vitro.

    Science.gov (United States)

    Kim, Hyemee; Banerjee, Nivedita; Sirven, Maritza A; Minamoto, Yasushi; Markel, Melissa E; Suchodolski, Jan S; Talcott, Stephen T; Mertens-Talcott, Susanne U

    2017-05-01

    This study investigated the potential role of the p70S6K1/HIF1α axis in the anti-inflammatory activities of pomegranate (Punica granatum L.) polyphenolics in dextran sodium sulfate (DSS)-induced colitis in Sprague-Dawley rats and in lipopolysaccharide (LPS)-treated CCD-18Co colon-myofibroblastic cells. Rats were administered either control (CT) or pomegranate beverage (PG), containing ellagic acid and ellagitannins, then exposed to three cycles of 3% DSS followed by a 2-week recovery period. PG protected against DSS-induced colon inflammation and ulceration (50% and 66.7%, P=.05 and .045, respectively), and decreased the Ki-67 proliferative index in the central and basal regions compared to the control. PG also significantly reduced the expression of proinflammatory cytokines (TNF-α and IL-1β), COX-2, and iNOS at mRNA and protein levels. In addition, the expression of p70S6K1 and HIF1α was reduced, while the tumor suppressor miR-145 was induced by PG. The intestinal microbiota of rats treated with PG showed a significant increase in Ruminococcaceae that include several butyrate producing bacteria (P=.03). In vitro, PG reduced the expression of p70S6K1 and HIF1α and induced miR-145 in a dose-dependent manner. The involvement of miR-145/p70S6K1 was confirmed by treating LPS-treated CCD-18Co cells with miR-145 antagomiR, where the pomegranate polyphenolics reversed the effects of the antagomiR for p70S6K1 mRNA and protein levels. These results suggest that pomegranate polyphenols attenuated DSS-induced colitis by modulating the miR-145/p70S6K/HIF1α axis, indicating potential use in therapeutic treatment of ulcerative colitis. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Mycobacterium tuberculosis PPE44 (Rv2770c) is involved in response to multiple stresses and promotes the macrophage expression of IL-12 p40 and IL-6 via the p38, ERK, and NF-κB signaling axis.

    Science.gov (United States)

    Yu, Zhaoxiao; Zhang, Chenhui; Zhou, Mingliang; Li, Qiming; Li, Hui; Duan, Wei; Li, Xue; Feng, Yonghong; Xie, Jianping

    2017-09-01

    Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains a formidable threat to global public health. The successful intracellular persistence of M. tuberculosis significantly contributes to the intractability of tuberculosis. Proline-glutamic acid (PE) and proline-proline-glutamic acid (PPE) are mycobacterial exclusive protein families that widely reported to be involved in the bacterial virulence, physiology and interaction with host. Rv2770c (PPE44), a predicted virulence factor, was up-regulated upon the infected guinea pig lungs. To investigate the role of Rv2770c, we heterologously expressed the PPE44 in the nonpathogenic fast-growing M. smegmatis strain. Subcellular location analysis demonstrated that Rv2770c is a cell wall associated protein, suggestive of a potential candidate involved in host-pathogen interaction. The Rv2770c can enhance M. smegmatis survival within macrophages and under stresses such as H 2 O 2 , SDS, diamide exposure, and low pH condition. M. smegmatis expressing Rv2770c is more virulent as testified by the increased death of macrophages and the increased expression of interlukin-6 (IL-6) and interlukin-12p40 (IL-12p40). Moreover, Rv2770c altered the secretion of IL-6 and IL-12p40 of macrophages via NF-κB, ERK1/2 and p38 MAPK axis. Taken together, this study implicated that Rv2770c was a virulent factor actively engaged in the interaction with host macrophage. Copyright © 2017. Published by Elsevier B.V.

  12. Acclimation of rainbow trout (Oncorhynchus mykiss) to low environmental pH does not involve an activation of the pituitary-interrenal axis, but evokes adjustments in branchial ultrastructure

    Energy Technology Data Exchange (ETDEWEB)

    Balm, P.H.M. (Nijmegen Univ. (Niger)); Pottinger, T.G. (Inst. of Freshwater Ecology, Ambleside, Cumbria (United Kingdom))

    1993-01-01

    Two strains of rainbow trout were exposed to soft water at pH 4.0 for 14 d, after ambient pH was reduced gradually. Several parameters, either indicators of acid stress or reportedly involved in the adaptive response to low pH, were monitored. No mortality occurred during the exposure period; feeding behaviour, haematocrit, and plasma protein levels were not affected. A transient depression of leucocrit was observed. A minor, but significant, hypochloremia and perturbations in plasma glucose levels occurred in acid-exposed fish from one strain only. There was no evidence of activation of the pituitary-interrenal axis in acid-exposed fish. Baseline plasma ACTH and cortisol levels were indistinguishable from those of control fish, and there was no evidence of sensitization to additional stress in acid-exposed fish. In vitro baseline and ACTH-stimulated cortisol secretion was not significantly different in the two groups. Ultrastructural evidence indicated an increased turnover rate of chloride cells and leucocyte infiltration in gills of acid-exposed fish. These results suggest that interrenal activation and catastrophic ion loss are not inevitable consequences of exposure of rainbow trout to pH 4.0 and that ultrastructural changes in the gills indicate locally regulated adaptive mechanisms. 53 refs., 4 figs., 2 tabs.

  13. Triple-axis spectrometer

    International Nuclear Information System (INIS)

    Toeroek, Gy.

    2001-01-01

    A triple-axis spectrometer has been designed for structural and dynamical studies of condensed matter. Because of the limited number of other operational equipment the triple axis spectrometer was used in a multi purpose regime, e.g. high resolution diffractometry, strain analysis, reflectometry, quasielastic and inelastic scattering. A polarization setup was also tested on this spectrometer. (R.P.)

  14. Gut-brain axis

    NARCIS (Netherlands)

    Romijn, Johannes A.; Corssmit, Eleonora P.; Havekes, Louis M.; Pijl, Hanno

    2008-01-01

    To summarize recent studies on the regulation and the functions of the gut-brain axis. Visual cues of food and food intake interact with the gut-brain axis at the level of the hypothalamus. However, the hypothalamic response to glucose intake is considerably altered in patients with type 2 diabetes

  15. Pathophysiology of the Effects of Alcohol Abuse on the Endocrine System.

    Science.gov (United States)

    Rachdaoui, Nadia; Sarkar, Dipak K

    2017-01-01

    Alcohol can permeate virtually every organ and tissue in the body, resulting in tissue injury and organ dysfunction. Considerable evidence indicates that alcohol abuse results in clinical abnormalities of one of the body's most important systems, the endocrine system. This system ensures proper communication between various organs, also interfacing with the immune and nervous systems, and is essential for maintaining a constant internal environment. The endocrine system includes the hypothalamic-pituitary-adrenal axis, the hypothalamic-pituitary-gonadal axis, the hypothalamic-pituitary-thyroid axis, the hypothalamic-pituitary-growth hormone/insulin-like growth factor-1 axis, and the hypothalamic-posterior pituitary axis, as well as other sources of hormones, such as the endocrine pancreas and endocrine adipose tissue. Alcohol abuse disrupts all of these systems and causes hormonal disturbances that may result in various disorders, such as stress intolerance, reproductive dysfunction, thyroid problems, immune abnormalities, and psychological and behavioral disorders. Studies in both humans and animal models have helped shed light on alcohol's effects on various components of the endocrine system and their consequences.

  16. Kisspeptin-mediated regulation of testicular activity of rats under the effect of gold nanoparticles

    Directory of Open Access Journals (Sweden)

    V. Y. Kalynovskyi

    2016-09-01

    Full Text Available There are a variety of biomedical applications of nanoparticles. They can be used as drug carriers, anti-tumor agents, biosensors and modulators of immune response. But full-scale real clinical application of nanomaterials requires a great deal of information on their safety and biotoxicity. Even traditionally harmless materials, like gold, can obtain toxic features when scaled to the nanosize. In vitro studies showed that nanoparticles can be geno- and cytotoxic, but their effects on the body as a whole remain largely a mystery. To shed some light on this, our study focused on the reproductive toxicity of nanomaterials. We synthesized 10–15 nm gold nanoparticles through the reduction of sodium tetrachloroaurate (III in an alkaline medium with the addition of sodium polyphosphate as a stabilizing agent. Next, these particles were administered intraperitoneally to young and old rats for 10 days. To test functional capabilities of the testes, we injected kisspeptin-10 or its antagonist peptide-234 intracerebroventricularly. These substances are known to stimulate or inhibit the central component of the hypothalamic-pituitary-gonadal axis respectively. After the routine histological procedures, we measured the diameter of seminiferous tubules and the nuclear cross-sectional area of Sertoli cells as markers of testicular spermatogenic activity and a cross-sectional area of the Leydig cells’ nuclei as a marker of testicular steroidogenesis. We found that injections of nanogold caused no significant changes in the young animals. At the same time, morphometric parameters of adult animals were significantly lower compared to control, although we observed no pathological changes in the tissue. Combined administration of gold nanoparticles and kisspeptin showed that the stimulatory effect of the latter was not observed at all. This is a specific feature of toxicants called “endocrine disruptors”. Moreover, we found morphological signs of

  17. Recovery of spermatogenesis following testosterone replacement therapy or anabolic-androgenic steroid use.

    Science.gov (United States)

    McBride, J Abram; Coward, Robert M

    2016-01-01

    The use of testosterone replacement therapy (TRT) for hypogonadism continues to rise, particularly in younger men who may wish to remain fertile. Concurrently, awareness of a more pervasive use of anabolic-androgenic steroids (AAS) within the general population has been appreciated. Both TRT and AAS can suppress the hypothalamic-pituitary-gonadal (HPG) axis resulting in diminution of spermatogenesis. Therefore, it is important that clinicians recognize previous TRT or AAS use in patients presenting for infertility treatment. Cessation of TRT or AAS use may result in spontaneous recovery of normal spermatogenesis in a reasonable number of patients if allowed sufficient time for recovery. However, some patients may not recover normal spermatogenesis or tolerate waiting for spontaneous recovery. In such cases, clinicians must be aware of the pathophysiologic derangements of the HPG axis related to TRT or AAS use and the pharmacologic agents available to reverse them. The available agents include injectable gonadotropins, selective estrogen receptor modulators, and aromatase inhibitors, but their off-label use is poorly described in the literature, potentially creating a knowledge gap for the clinician. Reviewing their use clinically for the treatment of hypogonadotropic hypogonadism and other HPG axis abnormalities can familiarize the clinician with the manner in which they can be used to recover spermatogenesis after TRT or AAS use.

  18. Recovery of spermatogenesis following testosterone replacement therapy or anabolic-androgenic steroid use

    Science.gov (United States)

    McBride, J Abram; Coward, Robert M

    2016-01-01

    The use of testosterone replacement therapy (TRT) for hypogonadism continues to rise, particularly in younger men who may wish to remain fertile. Concurrently, awareness of a more pervasive use of anabolic-androgenic steroids (AAS) within the general population has been appreciated. Both TRT and AAS can suppress the hypothalamic-pituitary-gonadal (HPG) axis resulting in diminution of spermatogenesis. Therefore, it is important that clinicians recognize previous TRT or AAS use in patients presenting for infertility treatment. Cessation of TRT or AAS use may result in spontaneous recovery of normal spermatogenesis in a reasonable number of patients if allowed sufficient time for recovery. However, some patients may not recover normal spermatogenesis or tolerate waiting for spontaneous recovery. In such cases, clinicians must be aware of the pathophysiologic derangements of the HPG axis related to TRT or AAS use and the pharmacologic agents available to reverse them. The available agents include injectable gonadotropins, selective estrogen receptor modulators, and aromatase inhibitors, but their off-label use is poorly described in the literature, potentially creating a knowledge gap for the clinician. Reviewing their use clinically for the treatment of hypogonadotropic hypogonadism and other HPG axis abnormalities can familiarize the clinician with the manner in which they can be used to recover spermatogenesis after TRT or AAS use. PMID:26908067

  19. Recovery of spermatogenesis following testosterone replacement therapy or anabolic-androgenic steroid use

    Directory of Open Access Journals (Sweden)

    J Abram McBride

    2016-01-01

    Full Text Available The use of testosterone replacement therapy (TRT for hypogonadism continues to rise, particularly in younger men who may wish to remain fertile. Concurrently, awareness of a more pervasive use of anabolic-androgenic steroids (AAS within the general population has been appreciated. Both TRT and AAS can suppress the hypothalamic-pituitary-gonadal (HPG axis resulting in diminution of spermatogenesis. Therefore, it is important that clinicians recognize previous TRT or AAS use in patients presenting for infertility treatment. Cessation of TRT or AAS use may result in spontaneous recovery of normal spermatogenesis in a reasonable number of patients if allowed sufficient time for recovery. However, some patients may not recover normal spermatogenesis or tolerate waiting for spontaneous recovery. In such cases, clinicians must be aware of the pathophysiologic derangements of the HPG axis related to TRT or AAS use and the pharmacologic agents available to reverse them. The available agents include injectable gonadotropins, selective estrogen receptor modulators, and aromatase inhibitors, but their off-label use is poorly described in the literature, potentially creating a knowledge gap for the clinician. Reviewing their use clinically for the treatment of hypogonadotropic hypogonadism and other HPG axis abnormalities can familiarize the clinician with the manner in which they can be used to recover spermatogenesis after TRT or AAS use.

  20. Effects of chronic exposure to cefadroxil and cefradine on Daphnia magna and Oryzias latipes.

    Science.gov (United States)

    Kim, Bokyung; Ji, Kyunghee; Kho, Younglim; Kim, Pan-Gyi; Park, Kyunghwa; Kim, Kyungtae; Kim, Youngsuk; Kim, Ki-Tae; Choi, Kyungho

    2017-10-01

    Cefadroxil and cefradine have frequently been detected in surface waters, however toxicological studies in aquatic organisms have mostly been limited to acute lethal effects. In the present study, endocrine disruption caused by cefadroxil and cefradine, and its underlying mechanism were investigated by chronic exposure of Daphnia magna (21 d) and Oryzias latipes (120 d). In medaka fish, the effects on growth, mortality, and reproduction, as well as on the levels of hormones and genes related to the hypothalamic-pituitary-gonad (HPG) axis, were investigated after 120 d exposure. In D. magna, the chronic effects on growth were observed at the highest concentration of 83.0 mg L -1 cefadroxil and 80.8 mg L -1 cefradine. The growth of juvenile fish was significantly impaired by exposure to cefradine. Following exposure to cefadroxil and cefradine for 120 d, sex-dependent changes in E2 hormones were observed and their levels were supported by the regulation of genes along the HPG axis. We found that chronic exposure to cefadroxil and cefradine impaired growth and reproduction in a freshwater invertebrate and fish, and altered the levels of sex hormones and genes associated with the HPG axis in fish. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Developmental and contextual considerations for adrenal and gonadal hormone functioning during adolescence: Implications for adolescent mental health.

    Science.gov (United States)

    Marceau, Kristine; Ruttle, Paula L; Shirtcliff, Elizabeth A; Essex, Marilyn J; Susman, Elizabeth J

    2015-09-01

    Substantial research has implicated the hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonadal (HPG) axes independently in adolescent mental health problems, though this literature remains largely inconclusive. Given the cross-talk between the HPA and HPG axes and their increased activation in adolescence, a dual-axis approach that examines both axes simultaneously is proposed to predict the emergence and persistence of adolescent mental health problems. After briefly orienting readers to HPA and HPG axis functioning, we review the literature examining associations between hormone levels and changes with behavior during adolescence. Then, we provide a review of the literature supporting examination of both axes simultaneously and present the limited research that has taken a dual-axis approach. We propose future directions including consideration of between-person and within-person approaches to address questions of correlated changes in HPA and HPG hormones. Potential moderators are considered to increase understanding of the nuanced hormone-behavior associations during key developmental transitions. © 2014 Wiley Periodicals, Inc.

  2. Non-analgesic effects of opioids: opioids and the endocrine system.

    Science.gov (United States)

    Elliott, Jennifer A; Opper, Susan E; Agarwal, Sonali; Fibuch, Eugene E

    2012-01-01

    Opioids are among the oldest known and most widely used analgesics. The application of opioids has expanded over the last few decades, especially in the treatment of chronic non-malignant pain. This upsurge in opioid use has been accompanied by the increasingly recognized occurrence of opioid-associated endocrinopathy. This may arise after exposure to enteral, parenteral, or neuraxial opioids. Opioid-associated endocrinopathy consists primarily of hypothalamic-pituitary-gonadal axis or hypothalamic-pituitary-adrenal axis dysfunction and may manifest with symptoms of hypogonadism, adrenal dysfunction, and other hormonal disturbances. Additionally, opioid related endocrine dysfunction may be coupled with such disorders as osteoporosis and mood disturbances including depression. Undesirable changes in pain sensitivity such as opioid-induced hyperalgesia, and reduced potency of opioid analgesia may also be potential consequences of chronic opioid consumption. Few studies to date have been able to establish what degree of opioid exposure, in terms of dose or duration of therapy, may predispose patients to opioid-associated endocrinopathy. This article will review the currently available literature concerning opioid-associated endocrinopathy and will provide recommendations for the evaluation, monitoring, and management of opioid-associated endocrinopathy and its other accompanying undesired effects.

  3. Prenatal corticosterone exposure programs growth, behavior, reproductive function and genes in the chicken

    Directory of Open Access Journals (Sweden)

    Abdelkareem A. Ahmed

    2016-07-01

    Full Text Available The aim of this review paper was to understand the role of prenatal corticosterone exposure on growth, aggressive behavior, reproductive performance and gene expression in the chicken. The phenotype, physiology, reproductive function and behavioral characteristics of an organism are not only influenced by genetic factors, but also by environmental factors that play a critical role in shaping offspring morphology. Exposure to excess glucocorticoids during embryonic development influences offspring growth, physiology and behaviors associated with alterations of hypothalamic-pituitary-adrenal axis, hypothalamic-pituitary-gonadal axis and serotonergic system gene expression. Another influential factor for phenotype, physiology and behavioral development is maternal derived steroid hormones that deposit in the egg. In avian species, maternal influences have aroused much attention after the discovery that avian eggs contain a variety of maternal derived steroid hormones. In addition, the environment condition during ontogeny has played a critical role in behavioral development. In avian species, for example laying chicken, high quality mother care produced chicks that were less fearful. Laying hen maternal care is found to reduce cannibalistic pecking phenomenon. Genetic selection and selection experiments will also play a critical role in animals breeding for the housing systems of the future. To optimize animal welfare and to reduce risks factors such as pecking behavior, fundamental approaches are required that merge selection of the optimal genotype with provision of a positive environment for parents and offspring, both throughout ontogeny and later life.

  4. STRESS AS PREDISPOSING FACTOR OF SOME CHRONIC DISEASES INCLUDING PERIODONTAL DISEASE

    Directory of Open Access Journals (Sweden)

    Dewi-Nurul M Dewi-Nurul

    2006-04-01

    Full Text Available Stress is hypothesized as a common pathway for several related chronic diseases of man. Psychosocial stress as modified by perceptions and coping by patients can lead to physical processes. Psychoneuroimmunologic (PNI studies have suggested that psychosocial stress can alter immune function and increase vulnerability to illnesses. The patients also have high sensitivity to periodontal disease (PD. This article describes the association of stress as a physiological response to diseases such as PD, rheumatoid arthritis (RA, and inflammatory bowel disease. The psychosocial stress can lead to physiological processes through 1 the hypothalamic-pituitary-adrenal (HPA axis leading to glucocortico-steroid secretion; 2 the autonomic nervous system, resulting in the release of catecholamine; or 3 the hypothalamic-pituitary-gonadal axis, resulting in the release of sex hormones. These processes may affect chronic diseases. It can be concluded that psychosocial stress in periodontal disease patients must be considered and social support must be provided in order to achieve an optimum periodontal therapy result.

  5. Vertical axis wind turbine

    International Nuclear Information System (INIS)

    Obretenov, V.; Tsalov, T.; Chakarov, T.

    2012-01-01

    In recent years, the interest in wind turbines with vertical axis noticeably increased. They have some important advantages: low cost, relatively simple structure, reliable packaging system of wind aggregate long period during which require no maintenance, low noise, independence of wind direction, etc.. The relatively low efficiency, however, makes them applicable mainly for small facilities. The work presents a methodology and software for approximately aerodynamic design of wind turbines of this type, and also analyzed the possibility of improving the efficiency of their workflow

  6. Vertical axis wind turbines

    Science.gov (United States)

    Krivcov, Vladimir [Miass, RU; Krivospitski, Vladimir [Miass, RU; Maksimov, Vasili [Miass, RU; Halstead, Richard [Rohnert Park, CA; Grahov, Jurij [Miass, RU

    2011-03-08

    A vertical axis wind turbine is described. The wind turbine can include a top ring, a middle ring and a lower ring, wherein a plurality of vertical airfoils are disposed between the rings. For example, three vertical airfoils can be attached between the upper ring and the middle ring. In addition, three more vertical airfoils can be attached between the lower ring and the middle ring. When wind contacts the vertically arranged airfoils the rings begin to spin. By connecting the rings to a center pole which spins an alternator, electricity can be generated from wind.

  7. Relation between diabetes mellitus and male fertility

    Directory of Open Access Journals (Sweden)

    Andy Petroianu

    2009-12-01

    Full Text Available Objective: The objective of the present study was to verify if there is any relation between diabetes mellitus and male infertility. Methods: the spermograms of 43 non-diabetic subjects and 12 diabetic patients (type 1 and 2 aged 20-60 years were compared. Spermiological findings in diabetic patients were compared with those of normal individuals of the same age. Serum testosterone, prolactin, follicle-stimulant hormone, luteinizing hormone, glucose and glycosilated hemoglobin were assayed in diabetic patients. Rresults: Six diabetic patients (four type 1 and two type 2 presented chronic complications attributed to neuropathy and vascular insufficiency. No difference was observed in the semen characteristics (odor, color, viscosity and pH between the control group and the diabetic patients. There were no differences between seminal concentrations and percentage of motile spermatozoa during the first hour of observation in the two groups (p < 0.05. Impotence was reported by four diabetic patients (33.3%. Erectile failure was associated with diabetic microangiopathy and neuropathy. There were no controls with impotence. No significant hormonal changes were found in the diabetic patients. Cconclusions: The present results suggest that neuropathy and vascular insufficiency  may be  implicated in sexual dysfunction in type 1 and 2 diabetic patients, without significantly affecting the hypothalamic-pituitary-gonadal axis.

  8. The novel neuropeptide phoenixin is highly co-expressed with nesfatin-1 in the rat hypothalamus, an immunohistochemical study.

    Science.gov (United States)

    Pałasz, Artur; Rojczyk, Ewa; Bogus, Katarzyna; Worthington, John J; Wiaderkiewicz, Ryszard

    2015-04-10

    The hypothalamus regulates a number of autonomic functions essential for homeostasis; therefore, investigations concerning hypothalamic neuropeptides and their functions and distribution are of great importance in contemporary neuroscience. Recently, novel regulatory factors expressed in the hypothalamus have been discovered, of which nesfatin-1 and phoenixin (PNX), show intriguing similarities in their brain distributions. There are currently few studies characterizing PNX expression, so it is imperative to accurately trace its localization, with particular attention to the hypothalamic nuclei and nesfatin-1 co-expression. Using fluorescence and classical immunohistochemical stainings on adult rat brain, we visualized the potential co-expression of nesfatin-1 and PNX immunoreactive cells. We have demonstrated a distinct PNX-immunoreactivity in 21-32% of cells in the arcuate nucleus, paraventricular nucleus, ventromedial and lateral hypothalamus. Nesfatin-1 expression reached 45-68% of all neurons in the same sites, while co-expression was strikingly seen in the vast majority (70-86%) of PNX-immunoreactive neurons in the rat hypothalamic nuclei. Our results demonstrate for the first time, a wide distribution of PNX in the hypothalamus which could implicate a potential functional relationship with nesfatin-1, possibly in the regulation of the hypothalamic-pituitary-gonadal axis or other autonomic functions, which require further study. Copyright © 2015. Published by Elsevier Ireland Ltd.

  9. Omega-3 polyunsaturated fatty acid docosahexaenoic acid and its role in exhaustive-exercise-induced changes in female rat ovulatory cycle.

    Science.gov (United States)

    Mostafa, Abeer F; Samir, Shereen M; Nagib, R M

    2018-04-01

    Exhaustive exercises can cause delayed menarche or menstrual cycle irregularities in females. Omega-3 polyunsaturated fatty acids (ω-3 PUFAs) are incorporated into a wide range of benefits in many physiological systems. Our work aimed to assess the role of ω-3 PUFA docosahexaenoic acid (DHA) on the deleterious effects of exhaustive exercise on the female reproductive system in rats. Virgin female rats were randomly divided into 4 groups (12 rats in each): control group, omega-3 group treated with DHA, exhaustive exercise group, and exhaustive exercised rats treated with DHA. Omega-3 was given orally to the rats once daily for 4 estrous cycles. Exhaustive exercises revealed lower levels in progesterone and gonadotropins together with histopathological decrease in number of growing follicles and corpora lutea. Moreover, the exercised rats showed low levels of ovarian antioxidants with high level of caspase-3 and plasma cortisol level that lead to disruption of hypothalamic-pituitary-gonadal axis. ω-3 PUFA DHA has beneficial effects on the number of newly growing follicles in both sedentary and exercised rats with decreasing the level of caspase-3 and increasing the antioxidant activity in ovaries. Exhaustive exercises can cause ovulatory problems in female rats that can be improved by ω-3 supplementation.

  10. Postinjection Muscle Fibrosis from Lupron

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    Erica Everest

    2015-01-01

    Full Text Available We describe the case of a 6.5-year-old girl with central precocious puberty (CPP, which signifies the onset of secondary sexual characteristics before the age of eight in females and the age of nine in males as a result of stimulation of the hypothalamic-pituitary-gonadal axis. Her case is likely related to her adoption, as children who are adopted internationally have much higher rates of CPP. She had left breast development at Tanner Stage 2, adult body odor, and mildly advanced bone age. In order to halt puberty and maximize adult height, she was prescribed a gonadotropin releasing hormone analog, the first line treatment for CPP. She was administered Lupron (leuprolide acetate Depot-Ped (3 months intramuscularly. After her second injection, she developed swelling and muscle pain at the injection site on her right thigh. She also reported an impaired ability to walk. She was diagnosed with muscle fibrosis. This is the first reported case of muscle fibrosis resulting from Lupron injection.

  11. Reduced male fertility in childhood cancer survivors

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    Sun Hee Lee

    2013-12-01

    Full Text Available With advances in cancer treatment, more pediatric cancer patients have increased their life expectancy. Because cancer-related therapy causes various physical and psychological problems, many male survivors experience later problems with thyroid and sexual functions, and with growth. As outcomes have improved, more survivors need to maintain their reproductive function to maximize their long-term quality of life. Cancer and cancer-related treatment can impair fertility by damage to the testes, to the hypothalamic-pituitary-gonadal axis, or to the genitourinary organs. Prior radiation therapy to the testes, the use of alkylating agents, and central hypogonadism further impair fertility in male survivors of childhood cancer. Following any course of chemotherapy, peripubertal maturation, any testicular volume changes, and symptoms of androgen deficiency should be monitored systematically. If patients request fertility testing, spermatogenesis status can be evaluated either directly by semen analysis or indirectly by determination of the levels of testosterone/gonadotropins and by monitoring any changes in testicular volume. According to the patient's condition, semen cryopreservation, hormonal therapy, or assisted reproduction technologies should be provided.

  12. Postnatal testosterone may be an important mediator of the association between prematurity and male neurodevelopmental disorders: a hypothesis.

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    Rice, Timothy R

    2017-04-01

    Children born premature are at risk for neurodevelopmental disorders, including autism and schizophrenia. This piece advances the hypothesis that altered androgen exposure observed in premature infants is an important mediator of the neurodevelopmental risk in males associated with prematurity. Specifically, the alterations of normative physiologic postnatal activations of the hypothalamic-pituitary-gonadal axis that occur in preterm males are hypothesized to contribute to the risk of neuropsychiatric pathology of prematurity through altered androgen-mediated organizational effects on the developing brain. The physiology of testosterone and male central nervous system development in full-term births is reviewed and compared to the developmental processes of prematurity. The effects of the altered testosterone physiology observed within prematurity outside of the central nervous system are reviewed as a segue into a discussion of the effects within the nervous system, with a special focus on autism spectrum disorders and attention deficit hyperactivity disorder. The explanatory power of this model is reviewed as a supplement to the preexisting models of prematurity and neurodevelopmental risk, including infection and other perinatal central nervous system insults. The emphasis is placed on altered androgen exposure as serving as just one among many mediators of neurodevelopmental risk that may be of interest for further research and evidence-based investigation. Implications for diagnosis, management and preventative treatments conclude the piece.

  13. Reproductive toxicity: Male and female reproductive systems as targets for chemical injury

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    Mattison, D.R.; Plowchalk, D.R.; Meadows, M.J.; Al-Juburi, A.Z.; Gandy, J.; Malek, A. (Univ. of Arkansas for Medical Sciences, Little Rock (USA))

    1990-03-01

    On the basis of current knowledge of reproductive biology and toxicology, it is apparent that chemicals affecting reproduction may elicit their effects at a number of sites in both the male and the female reproductive system. This multiplicity of targets is attributable to the dynamic nature of the reproductive system, in which the hypothalamic-pituitary-gonadal axis is controlled by precise positive and negative feedback mechanisms among its components. Interference by a xenobiotic at any level in either the male or the female reproductive system may ultimately impair hypothalamic or pituitary function. Normal gonadal processes such as spermatogenesis or oogenesis, ejaculation or ovulation, hormone production by Leydig or granulosa cells, and the structure or function of the accessory reproductive structures (e.g., epididymis, fallopian tube) also appear vulnerable to xenobiotics. The reproductive system is a complex one that requires local and circulating hormones for control. This brief review illustrates a system for characterizing the mechanism of action of reproductive toxicants, as well as for defining the sites available for disruption of reproduction. Unfortunately, at present, data addressing the actual vulnerability of reproduction are sorely lacking. However, when experiments have been conducted and combined with epidemiologic data or clinical observation, it has been possible to demonstrate impairment of reproductive processes by xenobiotics. The role of environmental exposure to xenobiotics in the increase in infertility that has been observed remains to be defined. 87 references.

  14. Transforming growth factor-beta1 null mutation causes infertility in male mice associated with testosterone deficiency and sexual dysfunction.

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    Ingman, Wendy V; Robertson, Sarah A

    2007-08-01

    TGFbeta1 is a multifunctional cytokine implicated in gonad and secondary sex organ development, steroidogenesis, and spermatogenesis. To determine the physiological requirement for TGFbeta1 in male reproduction, Tgfb1 null mutant mice on a Prkdc(scid) immunodeficient background were studied. TGFbeta1-deficient males did not deposit sperm or induce pseudopregnancy in females, despite an intact reproductive tract with morphologically normal penis, seminal vesicles, and testes. Serum and intratesticular testosterone and serum androstenedione were severely diminished in TGFbeta1-deficient males. Testosterone deficiency was secondary to disrupted pituitary gonadotropin secretion because serum LH and to a lesser extent serum FSH were reduced, and exogenous LH replacement with human chorionic gonadotropin (hCG) induced serum testosterone to control levels. In the majority of TGFbeta1-deficient males, spermatogenesis was normal and sperm were developmentally competent as assessed by in vitro fertilization. Analysis of sexual behavior revealed that although TGFbeta1 null males showed avid interest in females and engaged in mounting activity, intromission was infrequent and brief, and ejaculation was not attained. Administration of testosterone to adult males, even after neonatal androgenization, was ineffective in restoring sexual function; however, erectile reflexes and ejaculation could be induced by electrical stimulation. These studies demonstrate the profound effect of genetic deficiency in TGFbeta1 on male fertility, implicating this cytokine in essential roles in the hypothalamic-pituitary-gonadal axis and in testosterone-independent regulation of mating competence.

  15. What can allostasis tell us about anabolic-androgenic steroid addiction?

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    Hildebrandt, Tom; Yehuda, Rachel; Alfano, Lauren

    2011-08-01

    Anabolic-androgenic steroids (AASs) are synthetic hormones used by individuals who want to look better or perform better in athletics and at the gym. Their use raises an interesting paradox in which drug use is associated with a number of health benefits, but also the possibility of negative health consequences. Existing models of AAS addiction follow the traditional framework of drug abuse and dependence, which suggest that harmful use occurs as a result of the drug's ability to hijack the motivation-reward system. However, AASs, unlike typical drugs of abuse, are not used for acute intoxication effects or euphoria. Rather, AASs are used to affect the body through changes to the musculoskeletal system and the hypothalamic-pituitary-gonadal axis as opposed to stimulating the reward system. We offer an allostatic model of AAS addiction to resolve this inconsistency between traditional drug addiction and AAS addiction. This allostatic framework provides a way to (a) incorporate exercise into AAS misuse, (b) identify where AAS use transitions from recreational use into a drug problem, and (c) describe individual differences in vulnerability or resilience to AASs. Implications for this model of AAS addiction are discussed.

  16. Immunolocalization of Kisspeptin Associated with Amyloid-β Deposits in the Pons of an Alzheimer’s Disease Patient

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    Amrutha Chilumuri

    2013-01-01

    Full Text Available The pons region of the Alzheimer’s disease (AD brain is one of the last to show amyloid-β (Aβ deposits and has been suggested to contain neuroprotective compounds. Kisspeptin (KP is a hormone that activates the hypothalamic-pituitary-gonadal axis and has been suggested to be neuroprotective against Aβ toxicity. The localization of KP, plus the established endogenous neuroprotective compounds corticotropin releasing hormone (CRH and catalase, in tissue sections from the pons region of a male AD subject has been determined in relation to Aβ deposits. Results showed Aβ deposits also stained with KP, CRH, and catalase antibodies. At high magnification the staining of deposits was either KP or catalase positive, and there was only a limited area of the deposits with KP-catalase colocalization. The CRH does not bind Aβ, whilst both KP and catalase can bind Aβ, suggesting that colocalization in Aβ deposits is not restricted to compounds that directly bind Aβ. The neuroprotective actions of KP, CRH, and catalase were confirmed in vitro, and fibrillar Aβ preparations were shown to stimulate the release of KP in vitro. In conclusion, neuroprotective KP, CRH, and catalase all colocalize with Aβ plaque-like deposits in the pons region from a male AD subject.

  17. Traditional Chinese medicine valuably augments therapeutic options in the treatment of climacteric syndrome.

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    Eisenhardt, Sarah; Fleckenstein, Johannes

    2016-07-01

    Climacteric syndrome refers to recurring symptoms such as hot flashes, chills, headache, irritability and depression. This is usually experienced by menopausal women and can be related to a hormonal reorganization in the hypothalamic-pituitary-gonadal axis. In Traditional Chinese Medicine, originating 1000s of years ago, above-mentioned symptoms can be interpreted on the basis of the philosophic diagnostic concepts, such as the imbalance of Yin and Yang, the Zang-Fu and Basic substances (e.g. Qi, Blood and Essence). These concepts postulate balance and harmonization as the principle aim of a treatment. In this context, it is not astounding that one of the most prominent ancient textbooks dating back to 500-200 BC, Huang di Neijing: The Yellow Emperor's Classic of Internal Medicine gives already first instructions for diagnosis and therapy of climacteric symptoms. For therapy, traditional Chinese medicine comprises five treatment principles: Chinese herbal medicine, TuiNa (a Chinese form of manual therapy), nutrition, activity (e.g. QiGong) and acupuncture (being the most widespread form of treatment used in Europe). This review provides an easy access to the concepts of traditional Chinese medicine particularly regarding to climacteric syndrome and also focuses on current scientific evidence.

  18. Environmental and social influences on neuroendocrine puberty and behavior in macaques and other nonhuman primates

    Science.gov (United States)

    Stephens, Shannon B. Z.; Wallen, Kim

    2013-01-01

    Puberty is the developmental period when the hypothalamic-pituitary-gonadal (HPG) axis is activated, following a juvenile quiescent period, and reproductive capacity matures. Although pubertal events occur in a consistent sequence, there is considerable variation between individuals in the onset and timing of pubertal events, with puberty onset occurring earlier in girls than in boys. Evidence in humans demonstrates that social and environmental context influences the timing of puberty onset and may account for some of the observed variation. This review analyzes the nonhuman primate literature, focusing primarily on rhesus macaques (Macaca mulatta), to examine the social and environmental influences on puberty onset, how these factors influence puberty in males and females, and to review the relationship between puberty onset of adult neuroendocrine function and sexual behavior. Social and environmental factors influence the timing of puberty onset and pubertal events in nonhuman primates, as in humans, and the influences of these factors differ for males and females. In nonhuman primates, gonadal hormones are not required for sexual behavior, but modulate the frequency of occurrence of behavior, with social context influencing the relationship between gonadal hormones and sexual behavior. Thus, the onset of sexual behavior is independent of neuroendocrine changes at puberty; however, there are distinct behavioral changes that occur at puberty, which are modulated by social context. Puberty is possibly the developmental period when hormonal modulation of sexual behavior is organized, and thus, when social context interacts with hormonal state to strongly influence the expression of sexual behavior. PMID:23998667

  19. Hormonal Modulation in Aging Patients with Erectile Dysfunction and Metabolic Syndrome

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    Inês Campos Costa

    2013-01-01

    Full Text Available Erectile dysfunction (ED, metabolic syndrome (MetS, and hypogonadism are closely related, often coexisting in the aging male. Obesity was shown to raise the risk of ED and hypogonadism, as well as other endocrinological disturbances with impact on erectile function. We selected 179 patients referred for ED to our andrology unit, aiming to evaluate gonadotropins and estradiol interplay in context of ED, MetS, and hypogonadism. Patients were stratified into groups in accordance with the presence (or not of MetS and/or hypogonadism. Noticeable differences in total testosterone (TT and free testosterone (FT levels were found between patients with and without MetS. Men with MetS evidenced lower TT circulating levels with an increasing number of MetS parameters, for which hypertriglyceridemia and waist circumference strongly contributed. Regarding the hypothalamic-pituitary-gonadal axis, patients with hypogonadism did not exhibit raised LH levels. Interestingly, among those with higher LH levels, estradiol values were also increased. Possible explanations for this unexpected profile of estradiol may be the age-related adiposity, other estrogen-raising pathways, or even unknown mechanisms. Estradiol is possibly a molecule with further interactions beyond the currently described. Our results further enlighten this still unclear multidisciplinary and complex subject, raising new investigational opportunities.

  20. Association between plasma kisspeptin levels and adolescent gynecomastia.

    Science.gov (United States)

    Aluclu, Mustafa Arif; Sen, Selcuk; Cevik, Muazez

    2016-01-01

    Gynecomastia is defined as benign proliferation of male breast glandular tissue. To date, the pathophysiology of adolescent gynecomastia (AG) remains unclear. Kisspeptin is a polypeptide that plays an important role in the regulation of the hypothalamic-pituitary-gonadal hormonal axis. In this study, we investigated whether there is a relationship between kisspeptin and AG. This study included 40 males between 9 and 18 years of age diagnosed with gynecomastia. The control group consisted of 30 young healthy males in the same age range. The participants were evaluated with respect to anthropometric measurements (age, height, body weight, body mass index, breast and pubic stages and testicular volume). The levels of kisspeptin, follicle-stimulating hormone, luteinizing hormone, estradiol (E2), testosterone (T), and ratio of E2 to T were measured in both groups. The mean age was 13.8 years. There were no differences between the groups in terms of anthropometric parameters, plasma gonadotropin levels, estrogen levels, and E2/T (P > 0.05). Plasma kisspeptin (0.77 and 0.54 ng/mL, P < 0.05) and T (253.9 ng/dL and 117.9 ng/dL) levels were significantly higher in the AG group than in the control group (P < 0.001). Kisspeptin levels are an important factor in AG.

  1. Association between plasma kisspeptin levels and adolescent gynecomastia

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    Mustafa Arif Aluclu

    2016-01-01

    Full Text Available Background: Gynecomastia is defined as benign proliferation of male breast glandular tissue. To date, the pathophysiology of adolescent gynecomastia (AG remains unclear. Kisspeptin is a polypeptide that plays an important role in the regulation of the hypothalamic-pituitary-gonadal hormonal axis. In this study, we investigated whether there is a relationship between kisspeptin and AG. Materials and Methods: This study included 40 males between 9 and 18 years of age diagnosed with gynecomastia. The control group consisted of 30 young healthy males in the same age range. The participants were evaluated with respect to anthropometric measurements (age, height, body weight, body mass index, breast and pubic stages and testicular volume. The levels of kisspeptin, follicle-stimulating hormone, luteinizing hormone, estradiol (E2, testosterone (T, and ratio of E2 to T were measured in both groups. Results: The mean age was 13.8 years. There were no differences between the groups in terms of anthropometric parameters, plasma gonadotropin levels, estrogen levels, and E2/T (P > 0.05. Plasma kisspeptin (0.77 and 0.54 ng/mL, P < 0.05 and T (253.9 ng/dL and 117.9 ng/dL levels were significantly higher in the AG group than in the control group (P < 0.001. Conclusion: Kisspeptin levels are an important factor in AG.

  2. Developing confidence in adverse outcome pathway-based ...

    Science.gov (United States)

    An adverse outcome pathway (AOP) description linking inhibition of aromatase (cytochrome P450 [cyp] 19) to reproductive dysfunction was reviewed for scientific and technical quality and endorsed by the OECD. An intended application of the AOP framework is to support the use of mechanistic or pathway-based data to infer or predict chemical hazards and apical adverse outcomes. As part of this work, ToxCast high throughput screening data were used to identify a chemicals’ ability to inhibit aromatase activity in vitro. Twenty-four hour in vivo exposures, focused on effects on production and circulating concentrations of 17β-estradiol (E2), key events in the AOP, were conducted to verify in vivo activity. Based on these results, imazalil was selected as a case study chemical to test an AOP-based hazard prediction. A computational model of the fish hypothalamic-pituitary-gonadal-liver axis and a statistically-based model of oocyte growth dynamics were used to predict impacts of different concentrations of imazalil on multiple key events along the AOP, assuming continuous exposure for 21 d. Results of the model simulations were used to select test concentrations and design a fathead minnow reproduction study in which fish were exposed to 20, 60, or 200 µg imazalil/L for durations of 2.5, 10, or 21d. Within 60 h of exposure, female fathead minnows showed significant reductions in ex vivo production of E2, circulating E2 concentrations, and significant increases in

  3. Genetics of Hypogonadotropic Hypogonadism.

    Science.gov (United States)

    Topaloglu, A Kemal; Kotan, L Damla

    2016-01-01

    Hypogonadotropic hypogonadism (HH) often manifests as pubertal delay. A considerable proportion of cases of HH is due to genetic mutations. Recognizing those mutated genes and associated phenotypes may improve our diagnostic capabilities. GNRHR and TACR3 should be the first two genes to be screened in a clinical setting for equivocal cases such as constitutional delay in puberty versus idiopathic HH. In Kallmann syndrome (KS), according to the presence of certain accompanying clinical features, genetic screening for particular gene(s) may be prioritized: synkinesia (KAL1), dental agenesis (FGF8/FGFR1), bony anomalies (FGF8/FGFR1), and hearing loss (CHD7, SOX10). FEZF1 has recently been added to the growing list of KS genes. Also, discovery of mutations in KISS1/KISS1R and TAC3/TACR3 in kisspeptin and neurokinin B signaling, respectively, has provided major advancements in our understanding of the biology of the gonadotropin-releasing hormone pulse generator. Identification of further causative mutations accounting for the HH phenotype, which is now more feasible with the increasing popularity of whole exome sequencing, may provide deeper insight into the biology of the hypothalamic-pituitary-gonadal axis. © 2016 S. Karger AG, Basel.

  4. The inconspicuous penis in children.

    Science.gov (United States)

    Cimador, Marcello; Catalano, Pieralba; Ortolano, Rita; Giuffrè, Mario

    2015-04-01

    The term 'inconspicuous penis' refers to a group of anatomical abnormalities in which the penis looks smaller than is expected. Micropenis can be defined as 'true micropenis'--which results from a defect in the hypothalamic-pituitary-gonadal axis--and 'micropenis secondary to congenital anatomical anomalies of the surrounding and overlying structures'--also known as 'concealed penis'. The different forms of concealed penis include webbed penis, congenital megaprepuce and partially hidden penis caused by prepubic adiposity. This disorder can also have iatrogenic causes resulting from adhesions that are secondary to circumcision--this type of concealed penis is known as 'trapped penis'. However, in both groups, micropenis is defined as a stretched penile length that is at least 2.5 SD below the mean for the patient's age, but without any other penile defects. Patients with true micropenis can be managed with testosterone, which has demonstrated good penile elongation results in the long term. Surgery also has a pivotal role in reconstruction for elongating the penis and for correction of anatomical abnormalities in concealed penis.

  5. Endocrinology Update: Testicular Hypogonadism.

    Science.gov (United States)

    Heidelbaugh, Joel J

    2016-12-01

    Testicular hypogonadism, or androgen deficiency, is defined as a clinical condition resulting from failure of the testes to produce physiologic levels of testosterone and a normal number of spermatozoa because of disruption of the hypothalamic-pituitary-gonadal axis. Testosterone deficiency (TD) is defined as a serum level less than 300 ng/dL on a morning total testosterone test. It is estimated that more than one-third of men 45 years and older have testosterone deficiency. Associated symptoms include decreased libido, erectile dysfunction, decreased physical stamina and strength, depressed mood, fatigue, increased visceral adiposity, sleep disturbance, and/or poor concentration and memory. These conditions have a direct relationship with cardiometabolic parameters, including insulin resistance, hypertension, hyperlipidemia, and endothelial dysfunction in aging men. No single sign or symptom defines TD. Controversy exists relative to the benefits versus risks of testosterone replacement therapy in men with testicular hypogonadism. Benefits include improvements in the symptoms related to deficiency as well as cardiometabolic parameters, yet recent retrospective and observational trials have suggested an increased risk of cardiovascular mortality without a proven direct cause-and-effect relationship. Written permission from the American Academy of Family Physicians is required for reproduction of this material in whole or in part in any form or medium.

  6. Variants in congenital hypogonadotrophic hypogonadism genes identified in an Indonesian cohort of 46,XY under-virilised boys.

    Science.gov (United States)

    Ayers, Katie L; Bouty, Aurore; Robevska, Gorjana; van den Bergen, Jocelyn A; Juniarto, Achmad Zulfa; Listyasari, Nurin Aisyiyah; Sinclair, Andrew H; Faradz, Sultana M H

    2017-02-16

    Congenital hypogonadotrophic hypogonadism (CHH) and Kallmann syndrome (KS) are caused by disruption to the hypothalamic-pituitary-gonadal (H-P-G) axis. In particular, reduced production, secretion or action of gonadotrophin-releasing hormone (GnRH) is often responsible. Various genes, many of which play a role in the development and function of the GnRH neurons, have been implicated in these disorders. Clinically, CHH and KS are heterogeneous; however, in 46,XY patients, they can be characterised by under-virilisation phenotypes such as cryptorchidism and micropenis or delayed puberty. In rare cases, hypospadias may also be present. Here, we describe genetic mutational analysis of CHH genes in Indonesian 46,XY disorder of sex development patients with under-virilisation. We present 11 male patients with varying degrees of under-virilisation who have rare variants in known CHH genes. Interestingly, many of these patients had hypospadias. We postulate that variants in CHH genes, in particular PROKR2, PROK2, WDR11 and FGFR1 with CHD7, may contribute to under-virilisation phenotypes including hypospadias in Indonesia.

  7. The Effect of Antiepileptic Drug of Lamotrigine, on the Function of Reproductive Hormones in Male Rats

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    R. Khezri Motlagh

    2016-08-01

    Full Text Available Introduction: Lamotrigine is one of the never anti-epileptic drug. In this study the effects of lamotrigine have been observed on serum concentration of LH (Luteinizing hormone, FSH (Follicle-stimulating hormone, testosterone ,body and testis weight in male rat. Methods: The animal used in this experiment were 40 adult male rat from wistar race which were divided in to 5 group of 8.consisting of control group which received nothings, Sham group which received 0.2 ml distilled water via oral. Experimental group which received 100, 200, 400 mg/kg lamotrigine via oral after 14th day body weight were measured in all group and then the blood sample was taken from heart and concentration of LH.FSH, testosterone was measured. In addition the testis were separated and testis weight were measured in all group. Results: The result show that concentration of LH in experimental group did not show significant difference in compared with control group but in experimental group received 400mg/kg of lamotrigine  show a significant decrease in concentration of FSH and testosterone in comparison with control group .In addition lamotrigine had effect and testis weight in middle and high dose was reduce. Conclusion: Lamotrigine, an antiepileptic drug, reduced reproductive activity by inhibiting of hypothalamic-pituitary-gonadal axis in adult male rats.

  8. Preserving fertility in the hypogonadal patient: an update

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    Ranjith Ramasamy

    2015-04-01

    Full Text Available An increasing number of young and middle-aged men are seeking treatment for symptoms related to deficient levels of androgens (hypogonadism including depression, loss of libido, erectile dysfunction, and fatigue. The increase in prevalence of testosterone supplementation in general and anabolic steroid-induced hypogonadism specifically among younger athletes is creating a population of young men who are uniquely impacted by the testicular end-organ negative consequences of exogenous steroid use. Exogenous testosterone therapy can alter the natural regulation of the hypothalamic-pituitary-gonadal axis leading to impaired spermatogenesis with azoospermia being a serious possible result, thus rendering the individual infertile. For men of reproductive age who suffer from hypogonadal symptoms, preservation of fertility is an important aspect of their treatment paradigm. Treatment with human chorionic gonadotropin (hCG has shown the ability not only to reverse azoospermia brought on by testosterone supplementation therapy but also to help maintain elevated intratesticular testosterone levels. In addition, selective estrogen receptor modulators, often used with hCG have been shown both to elevate total testosterone levels and to maintain spermatogenesis in hypogonadal men.

  9. Long-Term Impact of Immunosuppressants at Therapeutic Doses on Male Reproductive System in Unilateral Nephrectomized Rats: A Comparative Study

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    Yehui Chen

    2013-01-01

    Full Text Available Cyclosporine, tacrolimus, and sirolimus are commonly used in renal transplant recipients to prevent rejection. However, information for comparative effects of these agents on the male productive system is extremely limited and controversial. In a physiologically and clinically relevant rat model of unilateral nephrectomy, we demonstrated that long-term oral administration of both cyclosporine and sirolimus at doses equivalent to the therapeutic levels used for postrenal transplant patients significantly affects testicular development and the hypothalamic-pituitary-gonadal axis accompanied by profound histological changes of testicular structures on both light and electron microscopic examinations. Spermatogenesis was also severely impaired as indicated by low total sperm counts along with reduction of sperm motility and increase in sperm abnormality after treatment with these agents, which may lead to male infertility. On the other hand, treatment with therapeutic dose of tacrolimus only induced mild reduction of sperm count without histological evidence of testicular injury. The current study clearly demonstrates that commonly used immunosuppressants have various impacts on male reproductive system even at therapeutic levels. Our data provide useful information for the assessment of male infertility in renal transplant recipients who wish to father children. Clinical trials to address these issues should be urged.

  10. The effects of Δ9-Tetrahydrocannabinole treatment on gonadal micro-vascularization and affected fertility examined by SEM and 3D-morphometry

    Science.gov (United States)

    Erlbacher, K. M. T.; Minnich, B.

    2015-10-01

    The present study focuses on the effects of Δ9-tetrahydrocannabinol (THC) on the reproductive system in nude rats with special emphasis on how Δ9-THC impacts the vascularization of testes which in turn indirectly influences fertility. Basically, Δ9-tetrahydrocannabinol (THC) causes not only negative (psychoactive) effects in the human body as cannabinole administration in medical use (dose-dependent) offers multiple new treatment opportunities such as pain relief or containment of various cancers. Concerning the reproductive system it strongly influences CB-receptors along the hypothalamic-pituitary-gonadal axis resulting in reduced plasma testosterone levels. There is also altered sperm quality parameters reported such as sperm motility or sperm count. On the other hand Δ9-THC effects endothelial growth factors (VEGF, Ang-1 etc.) respectively acts on their specific receptors which in turn modify angiogenesis and vascularization of tissues and organs (e.g. tumorous tissues). This leads to new therapeutical strategies in the suppression of various cancers by inhibiting (neo-)vascularization and in turn famishment of tumorous tissues (lack of nutrition supply). Here we studied the micro-vascularization of gonads in a long-term THC-treated nude rat model by vascular corrosion casting, SEM and 3D-morphometry.

  11. Adverse effects of doping with anabolic androgenic steroids (AAS) in competitive athletics, recreational sports and bodybuilding.

    Science.gov (United States)

    Vorona, Elena; Nieschlag, Eberhard

    2018-02-19

    Despite the fact that sports organizations and legislators have introduced various mechanisms to discourage athletes from using performance and appearance enhancing substances a high percentage of athletes admits to their unabated application. In competitive athletics, bodybuilding and in recreational sports anabolic androgenic steroids (AAS) continue to be the substances most abused. This review summarizes the side effects of AAS abuse on organs and system functions in both sexes. High doses of AAS cause a significant increase of erythrocytes und haemoglobin concentration, which may lead to thromboembolism, intracardiac thrombosis and stroke. Long-term AAS abusers have a higher incidence of arrhythmias, atherosclerosis, concentric left-ventricular myocardial hypertrophy with impaired diastolic function and also sudden cardiac death. Changes of liver function and structure, up to hepatocellular carcinoma, have been described, mainly in cases of chronic misuse of 17α-alkylated AAS. Sleeplessness, increased irritability, depressive mood status are often observed in AAS abuse. In former AAS abusers depression, anxiety and melancholy may persist for many years. Due to negative feedback in the regulation of the hypothalamic-pituitary-gonadal axis AAS can cause reversible suppression of spermatogenesis up to azoospermia. In women the changes most often caused by AAS abuse are hirsutism, irreversible deepening of voice, dysmenorrhoea, secondary amenorrhoea with anovulation and infertility. AAS abuse notwithstanding, under clinical conditions testosterone remains the most important hormone for substitution therapy of male hypogonadism.

  12. Role of melatonin on production and preservation of gametes and embryos: a brief review.

    Science.gov (United States)

    Cruz, Maria Helena Coelho; Leal, Claudia Lima Verde; da Cruz, Jurandir Ferreira; Tan, Dun-Xian; Reiter, Russel J

    2014-03-01

    The aim of this brief review is to clarify the role of melatonin in the production and preservation of mammalian gametes and embryos. Melatonin is an indoleamine synthesized from tryptophan in the pineal gland and other organs that operates as a hypothalamic-pituitary-gonadal axis modulator and regulates the waxing and waning of seasonal reproductive competence in photoperiodic mammals. A major function of the melatonin rhythm is to transmit information about the length of the daily photoperiod to the circadian and circannual systems in order to provide time-of-day and time-of-year information, respectively, to the organism. Melatonin is also a powerful antioxidant and anti-apoptotic agent, which is due to its direct scavenging of toxic oxygen derivatives and its ability to reduce the formation of reactive species. Mammalian gametes and embryos are highly vulnerable to oxidative stress due to the presence of high lipid levels; during artificial breeding procedures, these structures are exposed to dramatic changes in the microenvironment, which have a direct bearing on their function and viability. Free radicals influence the balance between oxidation-reduction reactions, disturb the transbilayer-phospholipid asymmetry of the plasma membrane and enhance lipid peroxidation. Melatonin, due to its amphiphilic nature, is undoubtedly useful in tissues by protecting them from free radical-mediated oxidative damage and cellular death. The supplementation of melatonin to semen extender or culture medium significantly improves sperm viability, oocyte competence and blastocyst development in vitro. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Temporal dynamic of adrenocortical and gonadal photo-responsiveness in male Japanese quail exposed to short days.

    Science.gov (United States)

    Dominchin, M F; Marin, R H; Palme, R; Busso, J M

    2014-10-01

    The study evaluated whether different short-term endocrine testicular and adrenocortical responses to short photoperiod exposure can persist over time and particularly when birds exhibit spontaneous cloacal gland recovery. At 11 wk of age, 33 male Japanese quail exposed to long photoperiod were switched to short photoperiod (8L:16D). Another group of males was kept under long photoperiod (n = 11; LD quail). After 5 wk of short photoperiod exposure, quail were classified as nonresponsive or responsive to short photoperiod, depending on whether the cloacal gland volume was above or below 1,000 mm(3) and with or without foam production, respectively. Since 11 wk of age and during a 20-wk period, droppings of all quail were collected to determine corticosterone and androgen metabolites (AM) by enzyme immunoassays. Cloacal gland volume was also determined weekly. Both short photoperiod nonresponsive (SD-NR) and responsive quail showed overall significantly lower (P SD-NR: 133.1 ± 15.5 > short photoperiod responsive: 61.6 ± 17.9 ng/g, respectively). Testicular and adrenocortical glands showed different degrees of activity associated with cloacal gland photoresponsiveness to short photoperiod manipulation. Our findings suggest long-term effects of short photoperiod, both in the hypothalamic-pituitary-gonadal and hypothalamic-pituitary-adrenocortical axis activity of quail, including males that exhibited spontaneous cloacal gland recovery. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Androgen modulation of social decision making mechanisms in the brain: an integrative and embodied perspective

    Directory of Open Access Journals (Sweden)

    Rui F Oliveira

    2014-07-01

    Full Text Available Apart from their role in reproduction androgens also respond to social challenges and this response has been seen as a way to regulate the expression of behaviour according to the perceived social environment (Challenge hypothesis, Wingfield et al. 1990. This hypothesis implies that social decision-making mechanisms localized in the central nervous system (CNS are open to the influence of peripheral hormones that ultimately are under the control of the CNS through the hypothalamic-pituitary-gonadal axis. Therefore, two puzzling questions emerge at two different levels of biological analysis: (1 Why does the brain, which perceives the social environment and regulates androgen production in the gonad, need feedback information from the gonad to adjust its social decision-making processes? (2 How does the brain regulate gonadal androgen responses to social challenges and how do these feedback into the brain? In this paper, we will address these two questions using the integrative approach proposed by Niko Tinbergen, who proposed that a full understanding of behaviour requires its analysis at both proximate (physiology, ontogeny and ultimate (ecology, evolution levels.

  15. Male isolation: a behavioral representation of the pheromonal 'female effect' in donkey (Equus asinus).

    Science.gov (United States)

    Carluccio, Augusto; Contri, Alberto; Amendola, Sonia; De Angelis, Elisabetta; De Amicis, Ippolito; Mazzatenta, Andrea

    2013-06-13

    The appearance of a decisive component of the sexual response to chemosexual signals in the male donkey was investigated through a comparison of the variations in the time-span of the behavioral classes and units for the natural versus induced breeding seasons. The results demonstrate that there are significant variations in the length of the appetitive sexual behavior (ASB) and consummatory sexual behavior (CSB) under these two reproductive conditions. These differences are analyzed for the ASB, which is adaptable, compared with the stereotyped CSB. For the ASB, male isolation is the most represented behavior of both the natural and induced breeding seasons. This is the key that allows the passage from courtship, which consists of appetitive behaviors, to copula, the consummatory behavior. This isolation appears to provide the time required to activate the hypothalamic-pituitary-gonadal axis through the chemosexual pathway of pheromone stimuli. This isolation is lengthened with induced breeding, supporting the hypothesis of the activation of the neuroendocrine system, which is not 'primed' outside the natural breeding season, and which is necessary to release the stereotyped CSB. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Pathway-based approaches for assessment of real-time exposure to an estrogenic wastewater treatment plant effluent on fathead minnow reproduction

    Science.gov (United States)

    Cavallin, Jenna E.; Jensen, Kathleen M.; Kahl, Michael D.; Villeneuve, Daniel L.; Lee, Kathy E.; Schroeder, Anthony L.; Mayasich, Joe; Eid, Evan P.; Nelson, Krysta R.; Milsk, Rebecca Y.; Blackwell, Brett R.; Berninger, Jason P.; LaLone, Carlie A.; Blanskma, Chad; Jicha, Terri M.; Elonen, Colleen M.; Johnson, Rodney C.; Ankley, Gerald T.

    2016-01-01

    Wastewater treatment plant (WWTP) effluents are known contributors of chemical mixtures into the environment. Of particular concern are endocrine-disrupting compounds, such as estrogens, which can affect the hypothalamic-pituitary-gonadal axis function in exposed organisms. The present study examined reproductive effects in fathead minnows exposed for 21 d to a historically estrogenic WWTP effluent. Fathead minnow breeding pairs were held in control water or 1 of 3 effluent concentrations (5%, 20%, and 100%) in a novel onsite, flow-through system providing real-time exposure. The authors examined molecular and biochemical endpoints representing key events along adverse outcome pathways linking estrogen receptor activation and other molecular initiating events to reproductive impairment. In addition, the authors used chemical analysis of the effluent to construct a chemical-gene interaction network to aid in targeted gene expression analyses and identifying potentially impacted biological pathways. Cumulative fecundity was significantly reduced in fish exposed to 100% effluent but increased in those exposed to 20% effluent, the approximate dilution factor in the receiving waters. Plasma vitellogenin concentrations in males increased in a dose-dependent manner with effluent concentration; however, male fertility was not impacted. Although in vitro analyses, analytical chemistry, and biomarker responses confirmed the effluent was estrogenic, estrogen receptor agonists were unlikely the primary driver of impaired reproduction. The results provide insights into the significance of pathway-based effects with regard to predicting adverse reproductive outcomes.

  17. Effects of aging on the male reproductive system.

    Science.gov (United States)

    Gunes, Sezgin; Hekim, Gulgez Neslihan Taskurt; Arslan, Mehmet Alper; Asci, Ramazan

    2016-04-01

    The study aims to discuss the effects of aging on the male reproductive system. A systematic review was performed using PubMed from 1980 to 2014. Aging is a natural process comprising of irreversible changes due to a myriad of endogenous and environmental factors at the level of all organs and systems. In modern life, as more couples choose to postpone having a child due to various socioeconomic reasons, research for understanding the effects of aging on the reproductive system has gained an increased importance. Paternal aging also causes genetic and epigenetic changes in spermatozoa, which impair male reproductive functions through their adverse effects on sperm quality and count as, well as, on sexual organs and the hypothalamic-pituitary-gonadal axis. Hormone production, spermatogenesis, and testes undergo changes as a man ages. These small changes lead to decrease in both the quality and quantity of spermatozoa. The offspring of older fathers show high prevalence of genetic abnormalities, childhood cancers, and several neuropsychiatric disorders. In addition, the latest advances in assisted reproductive techniques give older men a chance to have a child even with poor semen parameters. Further studies should investigate the onset of gonadal senesce and its effects on aging men.

  18. In vitro and in vivo effects of kisspeptin antagonists p234, p271, p354, and p356 on GPR54 activation.

    Directory of Open Access Journals (Sweden)

    C H J Albers-Wolthers

    Full Text Available Kisspeptins (KPs and their receptor (GPR54 or KiSS1R play a key-role in regulation of the hypothalamic-pituitary-gonadal axis and are therefore interesting targets for therapeutic interventions in the field of reproductive endocrinology. As dogs show a rapid and robust LH response after the administration of KP10, they can serve as a good animal model for research concerning KP signaling. The aims of the present study were to test the antagonistic properties of KP analogs p234, p271, p354, and p356 in vitro, by determining the intracellular Ca2+ response of CHEM1 cells that stably express human GPR54, and to study the in vivo effects of these peptides on basal plasma LH concentration and the KP10-induced LH response in female dogs. Exposure of the CHEM1 cells to KP-10 resulted in a clear Ca2+ response. P234, p271, p354, and p356 did not prevent or lower the KP10-induced Ca2+ response. Moreover, the in vivo studies in the dogs showed that none of these supposed antagonists lowered the basal plasma LH concentration and none of the peptides lowered the KP10-induced LH response. In conclusion, p234, p271, p354, and p356 had no antagonistic effects in vitro nor any effect on basal and kisspeptin-stimulated plasma LH concentration in female dogs.

  19. Neuroendocrine Regulation of Metabolism.

    Science.gov (United States)

    Cornejo, M P; Hentges, S T; Maliqueo, M; Coirini, H; Becu-Villalobos, D; Elias, C F

    2016-07-01

    Given the current environment in most developed countries, it is a challenge to maintain a good balance between calories consumed and calories burned, although maintenance of metabolic balance is key to good health. Therefore, understanding how metabolic regulation is achieved and how the dysregulation of metabolism affects health is an area of intense research. Most studies focus on the hypothalamus, which is a brain area that acts as a key regulator of metabolism. Among the nuclei that comprise the hypothalamus, the arcuate nucleus is one of the major mediators in the regulation of food intake. The regulation of energy balance is also a key factor ensuring the maintenance of any species as a result of the dependence of reproduction on energy stores. Adequate levels of energy reserves are necessary for the proper functioning of the hypothalamic-pituitary-gonadal axis. This review discusses valuable data presented in the 2015 edition of the International Workshop of Neuroendocrinology concerning the fundamental nature of the hormonal regulation of the hypothalamus and the impact on energy balance and reproduction. © 2016 British Society for Neuroendocrinology.

  20. Correlation of RDC/TMD axis I diagnoses and axis II pain-related disability. A multicenter study

    NARCIS (Netherlands)

    Manfredini, D.; Ahlberg, J.; Winocur, E.; Guarda-Nardini, L.; Lobbezoo, F.

    2011-01-01

    As part of an ongoing multicenter investigation involving four highly specialized tertiary clinics for temporomandibular disorders (TMD) treatment, retrospective analysis of Research Diagnostic Criteria for TMD (RDC/TMD) axis I and axis II data gathered on clinic and community cases were assessed

  1. Resolution of a triple axis spectrometer

    DEFF Research Database (Denmark)

    Nielsen, Mourits; Bjerrum Møller, Hans

    1969-01-01

    A new method for obtaining the resolution function for a triple-axis neutron spectrometer is described, involving a combination of direct measurement and analytical calculation. All factors which contribute to the finite resolution of the instrument may be taken into account, and Gaussian...... or experimentally determined probability distributions may be used. The application to the study of the dispersion relation for excitations in a crystal is outlined...

  2. Purinergic Signaling Pathways in Endocrine System

    Science.gov (United States)

    Bjelobaba, Ivana; Janjic, Marija M.; Stojilkovic, Stanko S.

    2015-01-01

    Adenosine-5′-triphosphate is released by neuroendocrine, endocrine, and other cell types and acts as an extracellular agonist for ligand-gated P2X cationic channels and G protein-coupled P2Y receptors in numerous organs and tissues, including the endocrine system. The breakdown of ATP by ectonucleotidases not only terminates its extracellular messenger functions, but also provides a pathway for the generation of two additional agonists: adenosine 5′-diphosphate, acting via some P2Y receptors, and adenosine, a native agonist for G protein-coupled adenosine receptors, also expressed in the endocrine system. This article provides a review of purinergic signaling pathways in the hypothalamic magnocellular neurosecretory cells and neurohypophysis, hypothalamic parvocellular neuroendocrine system, adenohypophysis, and effector glands organized in five axes: hypothalamic-pituitary-gonadal, hypothalamic-pituitary-thyroid, hypothalamic-pituitary-adrenal, hypothalamic-pituitary-growth hormone, and hypothalamic-pituitary-prolactin. We attempted to summarize current knowledge of purinergic receptor subtypes expressed in the endocrine system, including their roles in intracellular signaling, hormone secretion, and other cell functions. We also briefly review the release mechanism for adenosine-5′-triphosphate by neuroendocrine, endocrine and surrounding cells, the enzymes involved in adenosine-5′-triphosphate hydrolysis to adenosine-5′-diphosphate and adenosine, and the relevance of this pathway for sequential activation of receptors and termination of signaling. PMID:25960051

  3. Purinergic signaling pathways in endocrine system.

    Science.gov (United States)

    Bjelobaba, Ivana; Janjic, Marija M; Stojilkovic, Stanko S

    2015-09-01

    Adenosine-5'-triphosphate is released by neuroendocrine, endocrine, and other cell types and acts as an extracellular agonist for ligand-gated P2X cationic channels and G protein-coupled P2Y receptors in numerous organs and tissues, including the endocrine system. The breakdown of ATP by ectonucleotidases not only terminates its extracellular messenger functions, but also provides a pathway for the generation of two additional agonists: adenosine 5'-diphosphate, acting via some P2Y receptors, and adenosine, a native agonist for G protein-coupled adenosine receptors, also expressed in the endocrine system. This article provides a review of purinergic signaling pathways in the hypothalamic magnocellular neurosecretory cells and neurohypophysis, hypothalamic parvocellular neuroendocrine system, adenohypophysis, and effector glands organized in five axes: hypothalamic-pituitary-gonadal, hypothalamic-pituitary-thyroid, hypothalamic-pituitary-adrenal, hypothalamic-pituitary-growth hormone, and hypothalamic-pituitary-prolactin. We attempted to summarize current knowledge of purinergic receptor subtypes expressed in the endocrine system, including their roles in intracellular signaling, hormone secretion, and other cell functions. We also briefly review the release mechanism for adenosine-5'-triphosphate by neuroendocrine, endocrine and surrounding cells, the enzymes involved in adenosine-5'-triphosphate hydrolysis to adenosine-5'-diphosphate and adenosine, and the relevance of this pathway for sequential activation of receptors and termination of signaling. Published by Elsevier B.V.

  4. The hypothalamo-pituitary-adrenal axis in major affective disorder

    DEFF Research Database (Denmark)

    Christensen, M V; Kessing, L V

    2001-01-01

    This paper reviews studies of the hypothalamo-pituitary-adrenal (HPA)-axis activity in patients with affective disorders. It is concluded that, despite methodological drawbacks in most studies, dysregulation of the HPA axis seems to be a consistent finding in a proportion of patients with affective...... disorder. The HPA axis is a complex neuroendocrine network with multiple integrated levels of control, and it is likely that the dysregulation involves abnormalities at several sites within the axis. At present, it is not clear whether the abnormalities are related to the affective episodes only...... or to the disorder itself. There is a need for prospective studies of larger samples of patients to be followed during successive affective episodes with a combination of measurements of the HPA-axis activity and brain imaging....

  5. Gut Microbiota-brain Axis.

    Science.gov (United States)

    Wang, Hong-Xing; Wang, Yu-Ping

    2016-10-05

    To systematically review the updated information about the gut microbiota-brain axis. All articles about gut microbiota-brain axis published up to July 18, 2016, were identified through a literature search on PubMed, ScienceDirect, and Web of Science, with the keywords of "gut microbiota", "gut-brain axis", and "neuroscience". All relevant articles on gut microbiota and gut-brain axis were included and carefully reviewed, with no limitation of study design. It is well-recognized that gut microbiota affects the brain's physiological, behavioral, and cognitive functions although its precise mechanism has not yet been fully understood. Gut microbiota-brain axis may include gut microbiota and their metabolic products, enteric nervous system, sympathetic and parasympathetic branches within the autonomic nervous system, neural-immune system, neuroendocrine system, and central nervous system. Moreover, there may be five communication routes between gut microbiota and brain, including the gut-brain's neural network, neuroendocrine-hypothalamic-pituitary-adrenal axis, gut immune system, some neurotransmitters and neural regulators synthesized by gut bacteria, and barrier paths including intestinal mucosal barrier and blood-brain barrier. The microbiome is used to define the composition and functional characteristics of gut microbiota, and metagenomics is an appropriate technique to characterize gut microbiota. Gut microbiota-brain axis refers to a bidirectional information network between the gut microbiota and the brain, which may provide a new way to protect the brain in the near future.

  6. Gut Microbiota-brain Axis

    OpenAIRE

    Wang, Hong-Xing; Wang, Yu-Ping

    2016-01-01

    Objective: To systematically review the updated information about the gut microbiota-brain axis. Data Sources: All articles about gut microbiota-brain axis published up to July 18, 2016, were identified through a literature search on PubMed, ScienceDirect, and Web of Science, with the keywords of “gut microbiota”, “gut-brain axis”, and “neuroscience”. Study Selection: All relevant articles on gut microbiota and gut-brain axis were included and carefully reviewed, with no limitation of s...

  7. Thyroid stimulating hormone and serum, plasma, and platelet brain-derived neurotrophic factor during a 3-month follow-up in patients with major depressive disorder.

    Science.gov (United States)

    Baek, Ji Hyun; Kang, Eun-Suk; Fava, Maurizio; Mischoulon, David; Nierenberg, Andrew A; Lee, Dongsoo; Heo, Jung-Yoon; Jeon, Hong Jin

    2014-12-01

    Thyroid dysfunction and elevated thyroid stimulating hormone (TSH) are common in patients with depression. TSH might exert its function in the brain through blood levels of brain-derived neurotrophic factor (BDNF). BDNF decreases during depressed states and normalize after treatment. The gap is that the association between TSH and BDNF in patients with major depressive disorder (MDD) is unknown. We studied 105 subjects ≥18 years of age with MDD and measured serum, plasma, and platelet BDNF at baseline, 1 month and 3 months during antidepressant treatment. Other baseline measurements included hypothalamic-pituitary-thyroid axis hormones such as TSH, triiodothyronine (T3) and thyroxine (T4); hypothalamic-pituitary-adrenal (HPA) axis hormones and hypothalamic-pituitary-gonadal (HPG) axis hormones and prolactin. Linear mixed model effect analyses revealed that baseline TSH level was negatively associated with changes of serum BDNF from baseline to 3 months (F=7.58, p=0.007) after adjusting for age, sex, and body mass index, but was not associated with plasma and platelet BDNF. In contrast, T3 and T4, HPA axis hormones, HPG axis hormones, and prolactin were not associated with serum, plasma, or platelet BDNF levels. Patients in the highest quartile of TSH showed significantly lower serum BDNF than in the other quartiles (F=4.54, p=0.038), but no significant differences were found based on T3 and T4 levels. TSH was only measured at baseline. Higher TSH is associated with lower baseline and reduced the increase of serum BDNF levels during antidepressant treatment in patients with MDD. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Corticosteroid modulation and testosterone changes during alcohol intoxication affects voluntary alcohol drinking.

    Science.gov (United States)

    Eriksson, C J P; Etelälahti, T J; Apter, S J

    2017-06-01

    A number of studies have shown that stress and an activated hypothalamic-pituitary-adrenal (HPA) axis are associated with increased voluntary alcohol drinking. Recently, associations have been found between activated HPA and hypothalamic-pituitary-gonadal (HPG) axes in alcohol-preferring AA and non-preferring ANA, F2 (crossbred second generation from original AA and ANA), and Wistar rats. The aim of the present study has been to determine the role of corticosterone and alcohol-related testosterone-effects in subsequent alcohol drinking in AA, ANA, F2 and Wistar rats. The present study comprises of four substudies presenting new analyses of existing data, by which correlations between basal corticosterone levels, changes in testosterone levels during alcohol intoxications and subsequent voluntary alcohol consumption are investigated. The results displayed positive correlations between basal corticosterone levels and subsequent alcohol-mediated testosterone elevations, which was positively associated with voluntary alcohol consumption. The results also showed a negative correlation between basal corticosterone levels and alcohol-mediated testosterone decreases, which was negatively associated with alcohol consumption. In conclusion, the present study displays novel results, according to which the HPA axis, one hand, relates to testosterone elevation (potentially causing and/or strengthening reinforcement) during alcohol intoxication, which in turn may relate to higher voluntary alcohol consumption (AA rats). Vice versa, the HPA axis may also relate to alcohol-mediated testosterone decrease (causing testosterone reduction and disinforcement) and low-alcohol drinking (ANA, F2 and Wistar rats). In addition, the present results showed that alcohol-mediated testosterone changes may also, independently of the HPA axis, correlate with voluntary alcohol drinking, which indicate the impact of genetic factors. Thus, the role of the HPA-axis may be more related to situational

  9. Three axis attitude control system

    Science.gov (United States)

    Studer, Philip A. (Inventor)

    1988-01-01

    A three-axis attitude control system for an orbiting body comprised of a motor driven flywheel supported by a torque producing active magnetic bearing is described. Free rotation of the flywheel is provided about its central axis and together with limited angular torsional deflections of the flywheel about two orthogonal axes which are perpendicular to the central axis. The motor comprises an electronically commutated DC motor, while the magnetic bearing comprises a radially servoed permanent magnet biased magnetic bearing capable of producing cross-axis torques on the flywheel. Three body attitude sensors for pitch, yaw and roll generate respective command signals along three mutually orthogonal axes (x, y, z) which are coupled to circuit means for energizing a set of control coils for producing torques about two of the axes (x and y) and speed control of the flywheel about the third (z) axis. An energy recovery system, which is operative during motor deceleration, is also included which permits the use of a high-speed motor to perform effectively as a reactive wheel suspended in the magnetic bearing.

  10. Celiac axis stenosis: incidence and etiologies in asymptomatic individuals

    International Nuclear Information System (INIS)

    Park, Chang Min; Chung, Jin Wook; Kim, Hyun Beom; Shin, Sang June; Park, Jae Hyung

    2000-01-01

    To determine the incidence and etiologies of celiac axis stenosis in asymptomatic individuals. This prospective study involved 400 consecutive patients (male: 319, female: 81) referred to us for celiac arteriography between April and July 1999. When celiac axis branches were opacified by collateral circulation during superior mesenteric arteriography, the presence of celiac axis stenosis was suspected; lateral projection celiac arteriography was performed and the pressure gradient was measured. The indicators used to determine whether or not celiac axis stenosis was significant were luminal narrowing of more than 50% and a resultant pressure gradient of at least 10 mmHg. Its etiology was determined on the basis of angiographic appearances and CT findings. Twenty-nine patients (7.3%) had celiac axis stenosis. The etiology of the condition was extrinsic compression due to the median arcuate ligament in 16 patients (55%) and atherosclerosis in three (10%), while in ten (35%) it was not determined. The incidence of celiac axis stenosis did not vary significantly according to sex, age and the presence of calcified aortic plaque representing atherosclerosis. The incidence of hemodynamically significant celiac axis stenosis in this asymptomatic Korean population was 7.3% and the most important etiology was extrinsic compression by the median arcuate ligament of the diaphragm. Atherosclerosis was only a minor cause of the condition

  11. Vertical axis wind turbine airfoil

    Science.gov (United States)

    Krivcov, Vladimir; Krivospitski, Vladimir; Maksimov, Vasili; Halstead, Richard; Grahov, Jurij Vasiljevich

    2012-12-18

    A vertical axis wind turbine airfoil is described. The wind turbine airfoil can include a leading edge, a trailing edge, an upper curved surface, a lower curved surface, and a centerline running between the upper surface and the lower surface and from the leading edge to the trailing edge. The airfoil can be configured so that the distance between the centerline and the upper surface is the same as the distance between the centerline and the lower surface at all points along the length of the airfoil. A plurality of such airfoils can be included in a vertical axis wind turbine. These airfoils can be vertically disposed and can rotate about a vertical axis.

  12. Gut Microbiota-brain Axis

    Science.gov (United States)

    Wang, Hong-Xing; Wang, Yu-Ping

    2016-01-01

    Objective: To systematically review the updated information about the gut microbiota-brain axis. Data Sources: All articles about gut microbiota-brain axis published up to July 18, 2016, were identified through a literature search on PubMed, ScienceDirect, and Web of Science, with the keywords of “gut microbiota”, “gut-brain axis”, and “neuroscience”. Study Selection: All relevant articles on gut microbiota and gut-brain axis were included and carefully reviewed, with no limitation of study design. Results: It is well-recognized that gut microbiota affects the brain's physiological, behavioral, and cognitive functions although its precise mechanism has not yet been fully understood. Gut microbiota-brain axis may include gut microbiota and their metabolic products, enteric nervous system, sympathetic and parasympathetic branches within the autonomic nervous system, neural-immune system, neuroendocrine system, and central nervous system. Moreover, there may be five communication routes between gut microbiota and brain, including the gut-brain's neural network, neuroendocrine-hypothalamic-pituitary-adrenal axis, gut immune system, some neurotransmitters and neural regulators synthesized by gut bacteria, and barrier paths including intestinal mucosal barrier and blood-brain barrier. The microbiome is used to define the composition and functional characteristics of gut microbiota, and metagenomics is an appropriate technique to characterize gut microbiota. Conclusions: Gut microbiota-brain axis refers to a bidirectional information network between the gut microbiota and the brain, which may provide a new way to protect the brain in the near future. PMID:27647198

  13. Maternal gestational cortisol and testosterone are associated with trade-offs in offspring sex and number in a free-living rodent (Urocitellus richardsonii.

    Directory of Open Access Journals (Sweden)

    Calen P Ryan

    Full Text Available The adaptive manipulation of offspring sex and number has been of considerable interest to ecologists and evolutionary biologists. The physiological mechanisms that translate maternal condition and environmental cues into adaptive responses in offspring sex and number, however, remain obscure. In mammals, research into the mechanisms responsible for adaptive sex allocation has focused on two major endocrine axes: the hypothalamic pituitary adrenal (HPA axis and glucocorticoids, and the hypothalamic pituitary gonadal (HPG axis and sex steroids, particularly testosterone. While stress-induced activation of the HPA axis provides an intuitive model for sex ratio and litter size adjustment, plasma glucocorticoids exist in both bound and free fractions, and may be acting indirectly, for example by affecting plasma glucose levels. Furthermore, in female mammals, activation of the HPA axis stimulates the secretion of adrenal testosterone in addition to glucocorticoids (GCs. To begin to untangle these physiological mechanisms influencing offspring sex and number, we simultaneously examined fecal glucocorticoid metabolites, free and bound plasma cortisol, free testosterone, and plasma glucose concentration during both gestation and lactation in a free-living rodent (Urocitellus richardsonii. We also collected data on offspring sex and litter size from focal females and from a larger study population. Consistent with previous work in this population, we found evidence for a trade-off between offspring sex and number, as well as positive and negative correlations between glucocorticoids and sex ratio and litter size, respectively, during gestation (but not lactation. We also observed a negative relationship between testosterone and litter size during gestation (but not lactation, but no effect of glucose on either sex ratio or litter size. Our findings highlight the importance of binding proteins, cross-talk between endocrine systems, and temporal windows

  14. Effects of maternal exposure to social stress during pregnancy: consequences for mother and offspring.

    Science.gov (United States)

    Brunton, Paula J

    2013-01-01

    A suboptimal in utero environment, for example, as a result of maternal stress, can have detrimental effects on the pregnancy and long-term adverse 'programming' effects on the offspring. This article focuses on the effects of prenatal social stress on the mother, her pregnancy and the offspring, since these issues have ethological relevance in both animals and humans. The consequences of social stress exposure depend on when during pregnancy the stress occurs, and many of the effects on the offspring are sex specific. Social stress during early pregnancy tends to result in pregnancy loss, whereas stress exposure later in pregnancy, when the mother has already invested considerable resources in the foetuses, results in programmed offspring of low birth weight: a risk factor for various adulthood diseases. Neuroendocrine and behavioural responses to stress in the offspring are particularly sensitive to foetal programming by prenatal stress, indicated by enhanced hypothalamo-pituitary-adrenal (HPA) axis responses and increased anxiety behaviour, which result from permanent changes in the offspring's brain. The dysregulation of HPA axis function may also interfere with other systems, for example, the hypothalamic-pituitary-gonadal axis, as there is evidence for alterations in steroidogenesis, reproductive potential and impaired reproductive/social behaviours in prenatally stressed offspring. Prenatal social stress also programmes future maternal behaviour, highlighting the potential for negative phenotypes to be transmitted to future generations. The possible mechanisms through which maternal stress during pregnancy is transmitted to the foetuses and the foetal brain is programmed by prenatal stress and the potential to overwrite programming of the offspring are discussed.

  15. Life-cycle exposure to microcystin-LR interferes with the reproductive endocrine system of male zebrafish.

    Science.gov (United States)

    Su, Yujing; Li, Li; Hou, Jie; Wu, Ning; Lin, Wang; Li, Guangyu

    2016-06-01

    Recently, MC-LR reproductive toxicity drew great attention. Limited information was available on endocrine-disrupting effects of MC-LR on the reproduction system in fish. In the present study, zebrafish hatchlings (5 d post-fertilization) were exposed to 0, 0.3, 3 and 30μg/L MC-LR for 90 d until they reached sexual maturity. Male zebrafish were selected, and changes in growth and developmental parameters, testicular histological structure as well as the levels of gonadal steroid hormones were studied along with the related-gene transcriptional responses in the hypothalamic-pituitary-gonadal axis (HPG-axis). The results, for the first time, show a life cycle exposure to MC-LR causes growth inhibition, testicular damage and delayed sperm maturation. A significant decrease in T/E2 ratio indicated that MC-LR disrupted sex steroid hormones balance. The changes in transcriptional responses of HPG-axis related genes revealed that MC-LR promoted the conversion of T to E2 in circulating blood. It was also noted that vtg1 mRNA expression in the liver was up-regulated, which implied that MC-LR could induce estrogenic-like effects at environmentally relevant concentrations and long-term exposure. Our findings indicated that a life cycle exposure to MC-LR causes endocrine disruption with organic and functional damage of the testis, which might compromise the quality of life for the survivors and pose a potent threat on fish reproduction and thus population dynamics in MCs-contaminated aquatic environments. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Sheehan's syndrome in Xinjiang: Clinical characteristics and laboratory evaluation of 97 patients.

    Science.gov (United States)

    Du, Guo-li; Liu, Zhong-hua; Chen, Min; Ma, Rui; Jiang, Sheng; Shayiti, Miriguli; Zhu, Jun; Yusufu, Aibibai

    2015-01-01

    To evaluate the clinical and hormonal characteristics of patients with Sheehan's syndrome in Xinjiang, China. 97 cases diagnosed as Sheehan's syndrome in our hospital from 1999 to 2013 were retrospectively reviewed. The medical history, physical examination findings and hormonal profiles were documented and analyzed. The mean age at diagnosis was 43.7±12.4 years, with a mean diagnostic delay of 9.1±9.5 years (range, 1 month-35 years). 10 of our patients (10.3%) had a home birth. 96 of our patients (99.0%) had a history of obstetric hemorrhage. The most common clinical presentation included amenorrhea (80/97, 82.5%), agalactia (2/97, 74.2%) and loss of axillary or pubic hair (83/97, 85.6%). Seventy two of our patients (74.2%) failed to lactate and 80 of our patients (82.5%) failed to resume menstruation. Hypothalamic dysfunction included the hypothalamic-pituitary-gonadal axis (HPG) (LH deficiency: 77/83 patients, 92.8%; FSH deficiency: 73/83 patients, 88%; E2 deficiency: 62 of 82 patients,75.6%), the hypothalamic-pituitary-thyroid (HPT) axis (TSH deficiency: 77/93 patients, 82.8%, TT3 deficiency: 70/ 87 patients, 80.5%, TT4 deficiency: 72/87 patients, 82.8%) and the hypothalamus-pituitary-adrenal (HPA) axis (ACTH deficiency: 19/37 patients, 51.4%, cortisol deficiency: 49/64, 76.6%). Sheehan's syndrome is still common in Xinjiang, especially in rural areas. Long diagnosis delay in most of the patients indicates that women might be lacking correct diagnosis and treatment. Physicians need to be aware of the most important clues for diagnosis such as lack of lactation in the postpartum period and failure to resume menstruation.

  17. Optic axis-driven new horizons for hyperbolic metamaterials

    Directory of Open Access Journals (Sweden)

    Boardman Allan D.

    2015-01-01

    Full Text Available The broad assertion here is that the current hyperbolic metamaterial world is only partially served by investigations that incorporate only some limited version of anisotropy. Even modest deviations of the optic axis from the main propagation axis lead to new phase shifts, which not only compete with those created by absorption but end up dominating them. Some progress has been attempted in the literature by introducing the terms “asymmetric hyperbolic media”, but it appears that this kind of asymmetry only involves an optic axis at an angle to the interface of a uniaxial crystal. From a device point of view, many new prospects should appear and the outcomes of the investigations presented here yield a new general theory. It is emphasised that the orientation of the optic axis is a significant determinant in the resulting optical properties. Whereas for conventional anisotropic waveguides homogeneous propagating waves occur over a limited range of angular dispositions of the optic axis it is shown that for a hyperbolic guide a critical angular setting exists, above which the guided waves are always homogeneous. This has significant implications for metawaveguide designs. The resulting structures are more tolerant to optic axis misalignment.

  18. Clinical practice patterns in the assessment and management of low testosterone in men: an international survey of endocrinologists.

    Science.gov (United States)

    Grossmann, Mathis; Anawalt, Bradley D; Wu, Frederick C W

    2015-02-01

    To document current practices in the approach to low testosterone in older men. Given that recommendations are based on low-level evidence, we hypothesized that there would be a wide variability in clinical practice patterns. Members of all major endocrine and andrological societies were invited to participate in a Web-based survey of the diagnostic work-up and management of a hypothetical index case of a 61-year old overweight man presenting with symptoms suggestive of androgen deficiency, without evidence of hypothalamic-pituitary-gonadal (HPT) axis disease. Nine hundred and forty-three respondents (91·2% adult endocrinologists) from Northern America (63·7%), Europe (12·7%), Oceania (8·2%), Latin America and Caribbean (7·6%), and the Middle East, Asia, or Africa (7·8%) completed the survey. Response rates among participating societies ranged from 4·1-20·0%. There was a wide variability in clinical practice patterns, especially regarding biochemical diagnosis of androgen deficiency, exclusion of HPT axis pathology, and monitoring for prostate cancer. In a man with suggestive symptoms, 42·4% of participants would offer testosterone treatment below a serum total testosterone of 10·4 nmol/l (300 ng/dl). A total of 46·0% of participants were, over the last five years, 'less inclined' to prescribe testosterone to men with nonspecific symptoms and borderline testosterone levels, compared to 'no change' (29·3%) or 'more inclined' (24·7%), P management of lowered testosterone in older men, with deviations from current clinical practice guidelines, and a temporal trend towards increasing reluctance to prescribe testosterone to men without classical hypogonadism. These findings highlight the need for better evidence to guide clinicians regarding testosterone therapy. © 2014 John Wiley & Sons Ltd.

  19. Stress, captivity, and reproduction in a wild bird species.

    Science.gov (United States)

    Dickens, Molly J; Bentley, George E

    2014-09-01

    In seasonal species, glucocorticoid concentrations are often highest during the breeding season. However, the role of increased hypothalamic-pituitary-adrenal (HPA) activity in the regulation of reproduction remains poorly understood. Our study is the first, to our knowledge, to document reproductive consequences of a non-pharmacological hindrance to seasonal HPA fluctuations. Using wild-caught male and female European starlings (Sturnus vulgaris) housed in an outdoor, semi-natural environment, we divided birds into two mixed-sex groups. One group remained in the outdoor aviary, where starlings breed at the appropriate time of year. The other group was transferred into an indoor flight aviary, where we predicted reproductive suppression to occur. We measured changes in corticosterone (CORT) at baseline and stress-induced concentrations prior to group separation and at the experiment's conclusion. After ten days, the birds showed remarkable differences in breeding behavior and HPA activity. Outdoor birds exhibited increases in baseline and stress-induced CORT and progressed into active breeding (pairing, nest building, egg laying, etc.). In contrast, indoor birds displayed no change in baseline or stress-induced CORT and few signs of active breeding. We found significant sex and treatment effects on expression of HPA and hypothalamic-pituitary-gonadal (HPG) axis elements, suggesting sex-specific regulatory mechanisms. Our data suggest a novel, facilitating role for the HPA axis in the transition between early breeding and active breeding in a wild, seasonal avian species. In addition, understanding how changes in housing condition affect seasonal HPA fluctuations may help alleviate barriers to breeding wild animals in captivity. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. GnRH neurons of young and aged female rhesus monkeys co-express GPER but are unaffected by long-term hormone replacement.

    Science.gov (United States)

    Naugle, Michelle M; Gore, Andrea C

    2014-01-01

    Menopause is caused by changes in the function of the hypothalamic-pituitary-gonadal axis that controls reproduction. Hypophysiotropic gonadotropin-releasing hormone (GnRH) neurons in the hypothalamus orchestrate the activity of this axis and are regulated by hormonal feedback loops. The mechanisms by which GnRH responds to the primary regulatory sex steroid hormone, estradiol (E2), are still poorly understood in the context of menopause. Our goal was to determine whether the G protein-coupled estrogen receptor (GPER) is co-expressed in adult primate GnRH neurons and whether this changes with aging and/or E2 treatment. We used immunofluorescence double-labeling to characterize the co-expression of GPER in GnRH perikarya and terminals in the hypothalamus. Young and aged rhesus macaques were ovariectomized and given long-term (~2-year) hormone treatments (E2, E2 + progesterone, or vehicle) selected to mimic currently prescribed hormone replacement therapies used for the alleviation of menopausal symptoms in women. We found that about half of GnRH perikarya co-expressed GPER, while only about 12% of GnRH processes and terminals in the median eminence (ME) were double-labeled. Additionally, many GPER-labeled processes were in direct contact with GnRH neurons, often wrapped around the perikarya and processes and in close proximity in the ME. These results extend prior work by showing robust co-localization of GPER in GnRH in a clinically relevant model, and they support the possibility that GPER-mediated E2 regulation of GnRH occurs both in the soma and terminals in nonhuman primates.

  1. Social hierarchy modulates responses of fish exposed to contaminants of emerging concern.

    Directory of Open Access Journals (Sweden)

    Jelena Ivanova

    Full Text Available Many organisms, including the fathead minnow (Pimephales promelas, a toxicological model organism, establish social hierarchies. The social rank of each male in a population is under the control of the hypothalamic-pituitary-gonadal (HPG axis mainly through regulation of circulating androgen concentrations, which in turn drive the expression of secondary sex characteristics (SSCs. As dominant and subordinate males in an exposure study are initially under different physiological conditions (i.e., differing plasma androgen concentrations, we proposed that they belong to different subpopulations in the context of exposure to compounds that may interact with the HPG axis. Using a meta-analysis of our data from several previously published studies, we corroborated the hypothesis that social status, as indicated by SSCs, results in distinct clusters (eigenvalues >0.8 explaining >80% of variability with differential expression of plasma vitellogenin, a commonly used biomarker of exposure to contaminants of emerging concern (CEC. Furthermore, we confirmed our predictions that exposure to estrogenic CECs would homogenize plasma vitellogenin response (E1: cluster mean SSC values decreased to 4.33 and 4.86 relative to those of control; E2: decreased to 4.8 and 5.37 across the social hierarchy. In contrast, serotonin-specific reuptake inhibitors expand this response range (cluster mean SSC increased to 5.21 and 6.5 relative to those of control. Our results demonstrated that social hierarchies in male fathead minnows result in heterogeneous responses to chemical exposure. These results represent a cautionary note for the experimental design of single-sex exposure studies. We anticipate our study to be a starting point for the re-evaluation of toxicological data analyses in single sex exposure experiments.

  2. Acute stress may induce ovulation in women

    Directory of Open Access Journals (Sweden)

    Cano Antonio

    2010-05-01

    Full Text Available Abstract Background This study aims to gather information either supporting or rejecting the hypothesis that acute stress may induce ovulation in women. The formulation of this hypothesis is based on 2 facts: 1 estrogen-primed postmenopausal or ovariectomized women display an adrenal-progesterone-induced ovulatory-like luteinizing hormone (LH surge in response to exogenous adrenocorticotropic hormone (ACTH administration; and 2 women display multiple follicular waves during an interovulatory interval, and likely during pregnancy and lactation. Thus, acute stress may induce ovulation in women displaying appropriate serum levels of estradiol and one or more follicles large enough to respond to a non-midcycle LH surge. Methods A literature search using the PubMed database was performed to identify articles up to January 2010 focusing mainly on women as well as on rats and rhesus monkeys as animal models of interaction between the hypothalamic-pituitary-adrenal (HPA and hypothalamic-pituitary-gonadal (HPG axes. Results Whereas the HPA axis exhibits positive responses in practically all phases of the ovarian cycle, acute-stress-induced release of LH is found under relatively high plasma levels of estradiol. However, there are studies suggesting that several types of acute stress may exert different effects on pituitary LH release and the steroid environment may modulate in a different way (inhibiting or stimulating the pattern of response of the HPG axis elicited by acute stressors. Conclusion Women may be induced to ovulate at any point of the menstrual cycle or even during periods of amenorrhea associated with pregnancy and lactation if exposed to an appropriate acute stressor under a right estradiol environment.

  3. Transplantation of CD51+Stem Leydig Cells: A New Strategy for the Treatment of Testosterone Deficiency.

    Science.gov (United States)

    Zang, Zhi Jun; Wang, Jiancheng; Chen, Zhihong; Zhang, Yan; Gao, Yong; Su, Zhijian; Tuo, Ying; Liao, Yan; Zhang, Min; Yuan, Qunfang; Deng, Chunhua; Jiang, Mei Hua; Xiang, Andy Peng

    2017-05-01

    Stem Leydig cell (SLC) transplantation could provide a new strategy for treating the testosterone deficiency. Our previous study demonstrated that CD51 (also called integrin αv) might be a putative cell surface marker for SLCs, but the physiological function and efficacy of CD51 + SLCs treatment remain unclear. Here, we explore the potential therapeutic benefits of CD51 + SLCs transplantation and whether these transplanted cells can be regulated by the hypothalamic-pituitary-gonadal (HPG) axis. CD51 + cells were isolated from the testes of 12-weeks-old C57BL/6 mice, and we showed that such cells expressed SLC markers and that they were capable of self-renewal, extensive proliferation, and differentiation into multiple mesenchymal cell lineages and LCs in vitro. As a specific cytotoxin that eliminates Leydig cells (LCs) in adult rats, ethane dimethanesulfonate (EDS) was used to ablate LCs before the SLC transplantation. After being transplanted into the testes of EDS-treated rats, the CD51 + cells differentiated into mature LCs, and the recipient rats showed a partial recovery of testosterone production and spermatogenesis. Notably, a testosterone analysis revealed a circadian rhythm of testosterone secretion in cell-transplanted rats, and these testosterone secretions could be suppressed by decapeptyl (a luteinizing hormone-releasing hormone agonist), suggesting that the transplanted cells might be regulated by the HPG axis. This study is the first to demonstrate that CD51 + SLCs can restore the neuroendocrine regulation of testicular function by physiologically recovering the expected episodic changes in diurnal testosterone serum levels and that SLC transplantation may provide a new tool for the studies of testosterone deficiency treatment. Stem Cells 2017;35:1222-1232. © 2017 AlphaMed Press.

  4. Developmental exposure to the organophosphorus flame retardant tris(1,3-dichloro-2-propyl) phosphate: estrogenic activity, endocrine disruption and reproductive effects on zebrafish.

    Science.gov (United States)

    Wang, Qiangwei; Lam, James C W; Han, Jian; Wang, Xianfeng; Guo, Yongyong; Lam, Paul K S; Zhou, Bingsheng

    2015-03-01

    Tris(1,3-dichloro-2-propyl) phosphate (TDCPP) is an organophosphate flame retardant that is detectable in the environment and biota, prompting concern over its risk to wildlife and human health. Our objective was to investigate whether long-term exposure to low concentrations of TDCPP can affect fish reproduction. Zebrafish embryos were exposed to low concentrations (0, 4, 20 and 100μg/L) of TDCPP from 2h post-fertilization until sexual maturation. Exposure to TDCPP significantly increased plasma estradiol and testosterone levels in females, but had no effect in males. TDCPP exposure also caused a significant reduction in fecundity as indicated by decreased egg production. Real-time PCR was performed to examine selected genes in the hypothalamic-pituitary-gonadal (HPG) axis and liver. Principle component analysis (PCA) showed that sex hormone levels and fecundity were related to the mRNA level of several genes in the HPG axis. Furthermore, hepatic vitellogenin (vtg1 and vtg3) expression was upregulated in both females and males, suggesting TDCPP has estrogenic activity. Histological examination revealed promotion of oocyte maturation in the females, but retardation of spermiation in males. Reduced egg quality (e.g., egg diameter) and increased malformation rates were observed in the F1 generation. Chemical analysis showed significant levels of TDCPP and its metabolite bis(1,3-dichloro-2-propyl) phosphate in the gonads of males and females. In conclusion, long-term exposure to low concentrations of TDCPP impairs fish reproduction. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Social hierarchy modulates responses of fish exposed to contaminants of emerging concern

    Science.gov (United States)

    Ivanova, Jelena; Zhang, Shiju; Wang, Rong-Lin

    2017-01-01

    Many organisms, including the fathead minnow (Pimephales promelas), a toxicological model organism, establish social hierarchies. The social rank of each male in a population is under the control of the hypothalamic-pituitary-gonadal (HPG) axis mainly through regulation of circulating androgen concentrations, which in turn drive the expression of secondary sex characteristics (SSCs). As dominant and subordinate males in an exposure study are initially under different physiological conditions (i.e., differing plasma androgen concentrations), we proposed that they belong to different subpopulations in the context of exposure to compounds that may interact with the HPG axis. Using a meta-analysis of our data from several previously published studies, we corroborated the hypothesis that social status, as indicated by SSCs, results in distinct clusters (eigenvalues >0.8 explaining >80% of variability) with differential expression of plasma vitellogenin, a commonly used biomarker of exposure to contaminants of emerging concern (CEC). Furthermore, we confirmed our predictions that exposure to estrogenic CECs would homogenize plasma vitellogenin response (E1: cluster mean SSC values decreased to 4.33 and 4.86 relative to those of control; E2: decreased to 4.8 and 5.37) across the social hierarchy. In contrast, serotonin-specific reuptake inhibitors expand this response range (cluster mean SSC increased to 5.21 and 6.5 relative to those of control). Our results demonstrated that social hierarchies in male fathead minnows result in heterogeneous responses to chemical exposure. These results represent a cautionary note for the experimental design of single-sex exposure studies. We anticipate our study to be a starting point for the re-evaluation of toxicological data analyses in single sex exposure experiments. PMID:29049393

  6. Reproductive dysfunction and associated pathology in women undergoing military training.

    Science.gov (United States)

    Gifford, Robert M; Reynolds, R M; Greeves, J; Anderson, R A; Woods, D R

    2017-10-01

    Evidence from civilian athletes raises the question of whether reproductive dysfunction may be seen in female soldiers as a result of military training. Such reproductive dysfunction consists of impaired ovulation with or without long-term subfertility. A critical review of pertinent evidence following an extensive literature search. The evidence points towards reduced energy availability as the most likely explanation for exercise-induced reproductive dysfunction. Evidence also suggests that reproductive dysfunction is mediated by activation of the hypothalamic-pituitary-adrenal axis and suppression of the hypothalamic-pituitary-gonadal axis, with elevated ghrelin and reduced leptin likely to play an important role. The observed reproductive dysfunction exists as part of a female athletic triad, together with osteopenia and disordered eating. If this phenomenon was shown to exist with UK military training, this would be of significant concern. We hypothesise that the nature of military training and possibly field exercises may contribute to greater risk of reproductive dysfunction among female military trainees compared with exercising civilian controls. We discuss the features of military training and its participants, such as energy availability, age at recruitment, body phenotype, type of physical training, psychogenic stressors, altered sleep pattern and elemental exposure as contributors to reproductive dysfunction. We identify lines of future research to more fully characterise reproductive dysfunction in military women and suggest possible interventions that, if indicated, could improve their future well-being. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  7. The anatomical tibial axis: reliable rotational orientation in knee replacement.

    Science.gov (United States)

    Cobb, J P; Dixon, H; Dandachli, W; Iranpour, F

    2008-08-01

    The rotational alignment of the tibia is an unresolved issue in knee replacement. A poor functional outcome may be due to malrotation of the tibial component. Our aim was to find a reliable method for positioning the tibial component in knee replacement. CT scans of 19 knees were reconstructed in three dimensions and orientated vertically. An axial plane was identified 20 mm below the tibial spines. The centre of each tibial condyle was calculated from ten points taken round the condylar cortex. The tibial tubercle centre was also generated as the centre of the circle which best fitted eight points on the outside of the tubercle in an axial plane at the level of its most prominent point. The derived points were identified by three observers with errors of 0.6 mm to 1 mm. The medial and lateral tibial centres were constant features (radius 24 mm (SD 3), and 22 mm (SD 3), respectively). An anatomical axis was created perpendicular to the line joining these two points. The tubercle centre was found to be 20 mm (SD 7) lateral to the centre of the medial tibial condyle. Compared with this axis, an axis perpendicular to the posterior condylar axis was internally rotated by 6 degrees (SD 3). An axis based on the tibial tubercle and the tibial spines was also internally rotated by 5 degrees (sd 10). Alignment of the knee when based on this anatomical axis was more reliable than either the posterior surfaces or any axis involving the tubercle which was the least reliable landmark in the region.

  8. Role of Met Axis in Head and Neck Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Yiru, E-mail: xuyiru@umich.edu; Fisher, Gary J., E-mail: xuyiru@umich.edu [Department of Dermatology, University of Michigan, Ann Arbor, MI 48109 (United States)

    2013-11-26

    Head and neck cancer is the sixth most common type of cancer worldwide. Despite advances in aggressive multidisciplinary treatments, the 5-year survival rate for this dreadful disease is only 50%, mostly due to high rate of recurrence and early involvement of regional lymph nodes and subsequent metastasis. Understanding the molecular mechanisms responsible for invasion and metastasis is one of the most pressing goals in the field of head and neck cancer. Met, also known as hepatocyte growth factor receptor (HGFR), is a member of the receptor protein tyrosine kinase (RPTK) family. There is compelling evidence that Met axis is dysregulated and plays important roles in tumorigenesis, progression, metastasis, angiogenesis, and drug resistance in head and neck cancer. We describe in this review current understanding of Met axis in head and neck cancer biology and development of therapeutic inhibitors targeting Met axis.

  9. Systematic review of outcomes after distal pancreatectomy with coeliac axis resection for locally advanced pancreatic cancer

    NARCIS (Netherlands)

    Klompmaker, S.; de Rooij, T.; Korteweg, J. J.; van Dieren, S.; van Lienden, K. P.; van Gulik, T. M.; Busch, O. R.; Besselink, M. G.

    2016-01-01

    Pancreatic cancer involving the coeliac axis is considered unresectable by most guidelines, with a median survival of 6-11 months. A subgroup of these patients can undergo distal pancreatectomy with coeliac axis resection, but consensus on the value of this procedure is lacking. The evidence for

  10. Central regulation of the hypothalamo-pituitary-thyroid (HPT) axis: focus on clinical aspects

    NARCIS (Netherlands)

    Fliers, E.; Boelen, A.; van Trotsenburg, A. S. P.

    2014-01-01

    The hypothalamus is the most prominent brain region involved in setpoint regulation of the thyroid axis. It generates the diurnal thyroid-stimulating hormone (TSH) rhythm, and it plays a central role in the adaptation of the thyroid axis to environmental factors such as caloric deprivation or

  11. A systematic comparison of on-axis and off-axis transmission Kikuchi diffraction

    DEFF Research Database (Denmark)

    Niessen, F.; Burrows, A.; Fanta, A. Bastos da Silva

    2018-01-01

    Abstract The capabilities of the novel on-axis transmission Kikuchi diffraction (TKD) technique were explored in a systematic comparison with conventional off-axis TKD. The effect of experimental parameters on the appearance of on-axis and off-axis Kikuchi patterns was measured and discussed. In ...

  12. Social regulation of reproduction in male cichlid fishes.

    Science.gov (United States)

    Maruska, Karen P

    2014-10-01

    Social interactions and relative positions within a dominance hierarchy have helped shape the evolution of reproduction in many animals. Since reproduction is crucial in all animals, and rank typically regulates access to reproductive opportunities, understanding the mechanisms that regulate socially-induced reproductive processes is extremely important. How does position in a dominance hierarchy impact an individual's reproductive behavior, morphology, and physiology? Teleost fishes, and cichlids in particular, are ideally-suited models for studying how social status influences reproduction on multiple levels of biological organization. Here I review the current knowledge on the reproductive behavioral and physiological consequences of relative position in a dominance hierarchy, with a particular focus on male cichlids. Dominant and subordinate social status is typically associated with distinct differences in activity along the entire hypothalamic-pituitary-gonadal axis. Further, when transitions in social status occur between subordinate and dominant individuals, there are plastic changes from whole-organism behavior to molecular-level gene expression modifications that occur quickly. These rapid changes in behavior and physiology have allowed cichlids the flexibility to adapt to and thrive in their often dynamic physical and social environments. Studies in cichlid fishes have, and will continue, to advance our understanding of how the social environment can modulate molecular, cellular, and behavioral outcomes relevant to reproductive success. Future studies that take advantage of the extreme diversity in mating systems, reproductive tactics, and parental care strategies within the cichlid group will help generate hypotheses and careful experimental tests on the mechanisms governing the social control of reproduction in many vertebrates. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Exercise training, menstrual irregularities and bone development in children and adolescents.

    Science.gov (United States)

    Eliakim, Alon; Beyth, Yoram

    2003-08-01

    Weight bearing physical activity plays an important role in bone development. This is particularly important in children and adolescents since bone mineral density reaches about 90% of its peak by the end of the second decade, and because about one quarter of adult bone is accumulated during the two years surrounding the peak bone growth velocity. Recent studies suggested that the exercise-induced increase in bone mineralization is maturity dependent, and that there is a "window of opportunity" and a critical period for bone response to weight bearing exercise during early puberty and premenarchal years. This supports the idea that increase in physical activity during childhood and adolescence can prevent bone disorders (like osteoporosis) later in life. In contrast, strenuous physical activity may affect the female reproductive system and lead to "athletic amenorrhea". The prevalence of "athletic amenorrhea" is 4-20 times higher than the general population. As a consequence, bone demineralization may develop with increased risk of skeletal fragility, fractures, vertebral instability, and curvature. Menstrual abnormalities in the female athlete result from hypothalamic suppression of the spontaneous pulsatile secretion of gonadotropin releasing hormone. Recent studies suggested that reduced energy availability (increased energy expenditure with inadequate caloric intake) is the main cause of the central suppression of the hypothalamic pituitary-gonadal axis. Therefore, effort should be made to optimize the nutritional state of female athletes, and if not successful, to reduce the training load in order to prevent menstrual abnormalities, and deleterious bone effects in particular during the critical period of rapid bone growth.

  14. Suppressive effects of long-term exposure to P-nitrophenol on gonadal development, hormonal profile with disruption of tissue integrity, and activation of caspase-3 in male Japanese quail (Coturnix japonica).

    Science.gov (United States)

    Ahmed, Eman; Nagaoka, Kentaro; Fayez, Mostafa; Abdel-Daim, Mohamed M; Samir, Haney; Watanabe, Gen

    2015-07-01

    P-Nitrophenol (PNP) is considered to be one of nitrophenol derivatives of diesel exhaust particles. PNP is a major metabolite of some organophosphorus compounds. PNP is a persistent organic pollutant as well as one of endocrine-disrupting compounds. Consequently, bioaccumulation of PNP potentiates toxicity. The objectives of the current study were to assess in vivo adverse effects of long-term low doses of PNP exposure on reproductive system during development stage. Twenty-eight-day-old male Japanese quails were orally administered different doses of PNP (0, 0.01, 0.1, 1 mg/kg body weight) daily for 2.5 months. Testicular histopathology, hormones, caspase-3 (CASP3), and claudin-1 (CLDN1) tight junction protein, as well as plasma hormones were analyzed. The results revealed that long-term PNP exposure caused testicular histopathological changes such as vacuolation of spermatogenic cell and spermatocyte with significant testicular and cloacal gland atrophy. PNP activated CASP3 enzyme that is an apoptosis-related cysteine peptidase. Besides, it disrupted the expression of CLDN1. Furthermore, a substantial decrease in plasma concentrations of luteinizing hormone (LH) and testosterone was observed after 2 and 2.5 months in the PNP-treated groups. Meanwhile, the pituitary LH did not significantly change. Site of action of PNP may be peripheral on testicular development and/or centrally on the hypothalamic-pituitary-gonadal axis through reduction of pulsatile secretion of gonadotrophin-releasing hormone. Consequently, it may reduce the sensitivity of the anterior pituitary gland to secrete LH. In conclusion, PNP induced profound endocrine disruption in the form of hormonal imbalance, induction of CASP3, and disruption of CLDN1 expression in the testis. Hence, it may hinder the reproductive processes.

  15. Nutraceuticals in reproduction of bulls and stallions Nutracêuticos na reprodução de touros e garanhões

    Directory of Open Access Journals (Sweden)

    Rubens Paes de Arruda

    2010-07-01

    Full Text Available The industry has made available in the market a series of substances (nutraceuticals which intent would be to optimize the use of nutrients in some metabolic paths, influencing positively reproductive performance in animals. However, the response to the use of nutraceuticals varies according to the animal. As the organism is highly complex and in order to achieve a perfect activity of the hypothalamic-pituitary-gonadal axis, an ideal interaction in molecular basis is needed, where the nutraceuticals can have their direct action. The aim of this study was to review the function and research results using the main nutraceuticals (β carotene, vitamin A, L-carnitine, omegas 3, 6 and 9 and Gamma-oryzanol on reproductive characteristics of bulls and stallions.A indústria tem disponibilizado no mercado uma série de substâncias (nutracêuticos com a intenção de otimizar a utilização de nutrientes em algumas vias metabólicas, influenciando positivamente o desempenho reprodutivo dos animais. No entanto, a resposta ao uso de nutracêuticos varia de acordo com o animal. Como o organismo é altamente complexo e, a fim de alcançar perfeita atividade do eixo hipotálamo-hipófise-gonadal, uma interação ideal na base molecular é necessária, onde os nutracêuticos podem ter sua ação direta. O objetivo neste estudo foi revisar a função e resultados de pesquisas usando os principais nutracêuticos (β-caroteno, vitamina A, L-carnitina, ômegas 3, 6 e 9 e gama-orizanol sobre as características reprodutivas de touros e garanhões.

  16. Review: Regulatory mechanisms of gonadotropin-inhibitory hormone (GnIH synthesis and release in photoperiodic animals

    Directory of Open Access Journals (Sweden)

    Kazuyoshi eTsutsui

    2013-04-01

    Full Text Available Gonadotropin-inhibitory hormone (GnIH is a novel hypothalamic neuropeptide that was discovered in quail as an inhibitory factor for gonadotropin release. GnIH inhibits gonadotropin synthesis and release in birds through actions on gonadotropin-releasing hormone (GnRH neurons and gonadotropes, mediated via the GnIH receptor (GnIH-R, GPR147. Subsequently, GnIH was identified in mammals and other vertebrates. As in birds, mammalian GnIH inhibits gonadotropin secretion, indicating a conserved role for this neuropeptide in the control of the hypothalamic-pituitary-gonadal (HPG axis across species. Identification of the regulatory mechanisms governing GnIH expression and release is important in understanding the physiological role of the GnIH system. A nocturnal hormone, melatonin, appears to act directly on GnIH neurons through its receptor to induce expression and release of GnIH in quail, a photoperiodic bird. Recently, a similar, but opposite, action of melatonin on the inhibition of expression of mammalian GnIH was shown in hamsters and sheep, photoperiodic mammals. These results in photoperiodic animals demonstrate that GnIH expression is photoperiodically modulated via a melatonin-dependent process. Recent findings indicate that GnIH may be a mediator of stress-induced reproductive disruption in birds and mammals, pointing to a broad role for this neuropeptide in assessing physiological state and modifying reproductive effort accordingly. This paper summarizes the advances made in our knowledge regarding the regulation of GnIH synthesis and release in photoperiodic birds and mammals. This paper also discusses the neuroendocrine integration of environmental signals, such as photoperiods and stress, and internal signals, such as GnIH, melatonin and glucocorticoids, to control avian and mammalian reproduction.

  17. Discovering Genes Essential to the Hypothalamic Regulation of Human Reproduction Using a Human Disease Model: Adjusting to Life in the "-Omics" Era.

    Science.gov (United States)

    Stamou, M I; Cox, K H; Crowley, William F

    2016-02-01

    The neuroendocrine regulation of reproduction is an intricate process requiring the exquisite coordination of an assortment of cellular networks, all converging on the GnRH neurons. These neurons have a complex life history, migrating mainly from the olfactory placode into the hypothalamus, where GnRH is secreted and acts as the master regulator of the hypothalamic-pituitary-gonadal axis. Much of what we know about the biology of the GnRH neurons has been aided by discoveries made using the human disease model of isolated GnRH deficiency (IGD), a family of rare Mendelian disorders that share a common failure of secretion and/or action of GnRH causing hypogonadotropic hypogonadism. Over the last 30 years, research groups around the world have been investigating the genetic basis of IGD using different strategies based on complex cases that harbor structural abnormalities or single pleiotropic genes, endogamous pedigrees, candidate gene approaches as well as pathway gene analyses. Although such traditional approaches, based on well-validated tools, have been critical to establish the field, new strategies, such as next-generation sequencing, are now providing speed and robustness, but also revealing a surprising number of variants in known IGD genes in both patients and healthy controls. Thus, before the field moves forward with new genetic tools and continues discovery efforts, we must reassess what we know about IGD genetics and prepare to hold our work to a different standard. The purpose of this review is to: 1) look back at the strategies used to discover the "known" genes implicated in the rare forms of IGD; 2) examine the strengths and weaknesses of the methodologies used to validate genetic variation; 3)substantiate the role of known genes in the pathophysiology of the disease; and 4) project forward as we embark upon a widening use of these new and powerful technologies for gene discovery. (Endocrine Reviews 36: 603-621, 2015).

  18. Discovering Genes Essential to the Hypothalamic Regulation of Human Reproduction Using a Human Disease Model: Adjusting to Life in the “-Omics” Era

    Science.gov (United States)

    Stamou, M. I.; Cox, K. H.

    2015-01-01

    The neuroendocrine regulation of reproduction is an intricate process requiring the exquisite coordination of an assortment of cellular networks, all converging on the GnRH neurons. These neurons have a complex life history, migrating mainly from the olfactory placode into the hypothalamus, where GnRH is secreted and acts as the master regulator of the hypothalamic-pituitary-gonadal axis. Much of what we know about the biology of the GnRH neurons has been aided by discoveries made using the human disease model of isolated GnRH deficiency (IGD), a family of rare Mendelian disorders that share a common failure of secretion and/or action of GnRH causing hypogonadotropic hypogonadism. Over the last 30 years, research groups around the world have been investigating the genetic basis of IGD using different strategies based on complex cases that harbor structural abnormalities or single pleiotropic genes, endogamous pedigrees, candidate gene approaches as well as pathway gene analyses. Although such traditional approaches, based on well-validated tools, have been critical to establish the field, new strategies, such as next-generation sequencing, are now providing speed and robustness, but also revealing a surprising number of variants in known IGD genes in both patients and healthy controls. Thus, before the field moves forward with new genetic tools and continues discovery efforts, we must reassess what we know about IGD genetics and prepare to hold our work to a different standard. The purpose of this review is to: 1) look back at the strategies used to discover the “known” genes implicated in the rare forms of IGD; 2) examine the strengths and weaknesses of the methodologies used to validate genetic variation; 3) substantiate the role of known genes in the pathophysiology of the disease; and 4) project forward as we embark upon a widening use of these new and powerful technologies for gene discovery. PMID:26394276

  19. Study of the neuroendocrine and immunologic mechanism of fatigue caused by military operations

    Directory of Open Access Journals (Sweden)

    Xin LI

    2012-01-01

    Full Text Available Objective  To observe the regularity of the changes in neuroendocrine-immune system caused by fatigue due to military operations, and explore the mechanism by which fatigue occurs in military operations. Methods  The subjects were 240 soldiers belonging to a field artillery force. The medical history and physical examination were taken before military operations, and fatigue assessment scale was accomplished as well. The following variables were measured in all the subjects: pituitary-adrenal [adrenocorticotropic hormone (ACTH, cortical hormone (B, 24-h urinary free cortisol (UFC], pituitary-gonadal [luteinizing hormone (LH, testosterone (T, estradiol (E2], pituitary-thyroid functions [serum thyroid stimulating hormone (TSH, tetraiodothyronine (TT4, triiodothyronine (TT3, free thyroxine (FT4, and free triiodothyronine (FT3], and cellular immune parameters (CD3+, CD4+, CD8+, CD4+/CD8+, B, NK. After 7 d of large-scale and high-intensity field exercises, the above variables were again measured in all the subjects. Results  After high-intensity military operations, the unpleasant feelings were significantly increased, and the compulsive and psychotic scores significantly decreased in the soldiers. In addition, the pituitary-adrenal and pituitary-gonadal hormone levels also decreased (all PPPConclusion  The depressed psychological tolerance in soldiers is the psychological factor of fatigue after a high-intensity military operation. The hypocorticoidism and inhibition of hypothalamic-pituitary-gonadal axis are the pathophysiological basis of military operation fatigue. Suppression of immune function is an important reason for an increase of susceptibility to disease after high-intensity military operations.

  20. Complex biological pattern of fertility hormones in children and adolescents: a study of healthy children from the CALIPER cohort and establishment of pediatric reference intervals.

    Science.gov (United States)

    Konforte, Danijela; Shea, Jennifer L; Kyriakopoulou, Lianna; Colantonio, David; Cohen, Ashley H; Shaw, Julie; Bailey, Dana; Chan, Man Khun; Armbruster, David; Adeli, Khosrow

    2013-08-01

    Pediatric endocrinopathies are commonly diagnosed and monitored by measuring hormones of the hypothalamic-pituitary-gonadal axis. Because growth and development can markedly influence normal circulating concentrations of fertility hormones, accurate reference intervals established on the basis of a healthy, nonhospitalized pediatric population and that reflect age-, gender-, and pubertal stage-specific changes are essential for test result interpretation. Healthy children and adolescents (n = 1234) were recruited from a multiethnic population as part of the CALIPER study. After written informed parental consent was obtained, participants filled out a questionnaire including demographic and pubertal development information (assessed by self-reported Tanner stage) and provided a blood sample. We measured 7 fertility hormones including estradiol, testosterone (second generation), progesterone, sex hormone-binding globulin, prolactin, follicle-stimulating hormone, and luteinizing hormone by use of the Abbott Architect i2000 analyzer. We then used these data to calculate age-, gender-, and Tanner stage-specific reference intervals according to Clinical Laboratory Standards Institute C28-A3 guidelines. We observed a complex pattern of change in each analyte concentration from the neonatal period to adolescence. Consequently, many age and sex partitions were required to cover the changes in most fertility hormones over this period. An exception to this was prolactin, for which no sex partition and only 3 age partitions were necessary. This comprehensive database of pediatric reference intervals for fertility hormones will be of global benefit and should lead to improved diagnosis of pediatric endocrinopathies. The new database will need to be validated in local populations and for other immunoassay platforms as recommended by the Clinical Laboratory Standards Institute.

  1. Joint toxic effects of triazophos and imidacloprid on zebrafish (Danio rerio).

    Science.gov (United States)

    Wu, Shenggan; Li, Xinfang; Liu, Xinju; Yang, Guiling; An, Xuehua; Wang, Qiang; Wang, Yanhua

    2018-04-01

    Pesticide contamination is more often found as a mixture of different pesticides in water bodies rather than individual compounds. However, regulatory risk evaluation is mostly based on the effects of individual pesticides. In the present study, we aimed to investigate the individual and joint toxicities of triazophos (TRI) and imidacloprid (IMI) to the zebrafish (Danio rerio) using acute indices and various sublethal endpoints. Results from 96-h semi-static test indicated that the LC 50 values of TRI to D. rerio at multiple life stages (embryonic, larval, juvenile and adult stages) ranged from 0.49 (0.36-0.71) to 4.99 (2.06-6.81) mg a.i. L -1 , which were higher than those of IMI ranging from 26.39 (19.04-38.01) to 128.9 (68.47-173.6) mg a.i. L -1 . Pesticide mixtures of TRI and IMI displayed synergistic response to zebrafish embryos. Activities of carboxylesterase (CarE) and catalase (CAT) were significantly changed in most of the individual and joint exposures of pesticides compared with the control group. The expressions of 26 genes related to oxidative stress, cellular apoptosis, immune system, hypothalamic-pituitary-thyroid and hypothalamic-pituitary-gonadal axis at the mRNA level revealed that zebrafish embryos were affected by the individual or joint pesticides, and greater changes in the expressions of six genes (Mn-sod, CXCL-CIC, Dio1, Dio2, tsh and vtg1) were observed when exposed to joint pesticides compared with their individual pesticides. Taken together, the synergistic effects indicated that it was highly important to incorporate joint toxicity studies, especially at low concentrations, when assessing the risk of pesticides. Copyright © 2018 Elsevier Ltd. All rights reserved.

  2. MECHANISMS IN ENDOCRINOLOGY: Medical consequences of doping with anabolic androgenic steroids: effects on reproductive functions.

    Science.gov (United States)

    Nieschlag, Eberhard; Vorona, Elena

    2015-08-01

    Anabolic androgenic steroids (AASs) are appearance and performance-enhancing drugs (APEDs) used in competitive athletics, in recreational sports, and by body-builders. The global lifetime prevalence of AASs abuse is 6.4% for males and 1.6% for women. Many AASs, often obtained from the internet and dubious sources, have not undergone proper testing and are consumed at extremely high doses and in irrational combinations, also along with other drugs. Controlled clinical trials investigating undesired side effects are lacking because ethical restrictions prevent exposing volunteers to potentially toxic regimens, obscuring a causal relationship between AASs abuse and possible sequelae. Because of the negative feedback in the regulation of the hypothalamic-pituitary-gonadal axis, in men AASs cause reversible suppression of spermatogenesis, testicular atrophy, infertility, and erectile dysfunction (anabolic steroid-induced hypogonadism). Should spermatogenesis not recover after AASs abuse, a pre-existing fertility disorder may have resurfaced. AASs frequently cause gynecomastia and acne. In women, AASs may disrupt ovarian function. Chronic strenuous physical activity leads to menstrual irregularities and, in severe cases, to the female athlete triad (low energy intake, menstrual disorders and low bone mass), making it difficult to disentangle the effects of sports and AASs. Acne, hirsutism and (irreversible) deepening of the voice are further consequences of AASs misuse. There is no evidence that AASs cause breast carcinoma. Detecting AASs misuse through the control network of the World Anti-Doping Agency (WADA) not only aims to guarantee fair conditions for athletes, but also to protect them from medical sequelae of AASs abuse. © 2015 European Society of Endocrinology.

  3. Differential protein expression profile in the hypothalamic GT1-7 cell line after exposure to anabolic androgenic steroids.

    Science.gov (United States)

    Martínez-Rivera, Freddyson J; Pérez-Laspiur, Juliana; Santiago-Gascot, María E; Alemán-Reyes, Abner G; García-Santiago, Emanuel; Rodríguez-Pérez, Yolanda; Calo-Guadalupe, Cristhian; Otero-Pagán, Inelia; Ayala-Pagán, Roxsana N; Martínez, Magdiel; Cantres-Rosario, Yisel M; Meléndez, Loyda M; Barreto-Estrada, Jennifer L

    2017-01-01

    The abuse of anabolic androgenic steroids (AAS) has been considered a major public health problem during decades. Supraphysiological doses of AAS may lead to a variety of neuroendocrine problems. Precisely, the hypothalamic-pituitary-gonadal (HPG) axis is one of the body systems that is mainly influenced by steroidal hormones. Fluctuations of the hormonal milieu result in alterations of reproductive function, which are made through changes in hypothalamic neurons expressing gonadotropin-releasing hormone (GnRH). In fact, previous studies have shown that AAS modulate the activity of these neurons through steroid-sensitive afferents. To increase knowledge about the cellular mechanisms induced by AAS in GnRH neurons, we performed proteomic analyses of the murine hypothalamic GT1-7 cell line after exposure to 17α-methyltestosterone (17α-meT; 1 μM). These cells represent a good model for studying regulatory processes because they exhibit the typical characteristics of GnRH neurons, and respond to compounds that modulate GnRH in vivo. Two-dimensional difference in gel electrophoresis (2D-DIGE) and mass spectrometry analyses identified a total of 17 different proteins that were significantly affected by supraphysiological levels of AAS. Furthermore, pathway analyses showed that modulated proteins were mainly associated to glucose metabolism, drug detoxification, stress response and cell cycle. Validation of many of these proteins, such as GSTM1, ERH, GAPDH, PEBP1 and PDIA6, were confirmed by western blotting. We further demonstrated that AAS exposure decreased expression of estrogen receptors and GnRH, while two important signaling pathway proteins p-ERK, and p-p38, were modulated. Our results suggest that steroids have the capacity to directly affect the neuroendocrine system by modulating key cellular processes for the control of reproductive function.

  4. Delay of the Onset of Puberty in Female Rats by Prepubertal Exposure to T-2 Toxin

    Directory of Open Access Journals (Sweden)

    Rong Yang

    2015-11-01

    Full Text Available Growing evidence has revealed the deleterious influence of environmental and food contaminants on puberty onset and development in both animals and children, provoking an increasing health concern. T-2 toxin, a naturally-produced Type A trichothecene mycotoxin which is frequently found in cereal grains and products intended for human and animal consumption, has been shown to impair the reproduction and development in animals. Nevertheless, whether this trichothecene mycotoxin can disturb the onset of puberty in females remains unclear. To clarify this point, infantile female rats were given a daily intragastric administration of vehicle or 187.5 μg/kg body weight of T-2 toxin for five consecutive days from postnatal day 15 to 19, and the effects on puberty onset were evaluated in the present study. The results revealed that the days of vaginal opening, first dioestrus, and first estrus in regular estrous cycle were delayed following prepubertal exposure to T-2 toxin. The relative weights of reproductive organs uterus, ovaries, and vagina, and the incidence of corpora lutea were all diminished in T-2 toxin-treated rats. Serum levels of gonadotropins luteinizing hormone, follicle-stimulating hormone, and estradiol were also reduced by T-2 toxin treatment. The mRNA expressions of hypothalamic gonadotropin-releasing hormone (GnRH and pituitary GnRH receptor displayed significant reductions following exposure to T-2 toxin, which were consistent with the changes of serum gonadotropins, delayed reproductive organ development, and delayed vaginal opening. In conclusion, the present study reveals that prepubertal exposure to T-2 toxin delays the onset of puberty in immature female rats, probably by the mechanism of disturbance of hypothalamic-pituitary-gonadal (HPG axis function. Considering the vulnerability of developmental children to food contaminants and the relative high level of dietary intake of T-2 toxin in children, we think the findings of

  5. Reproductive system behavior following exposure of sustained delivery of npy antagonist in ovariectomized (ovx) rats.

    Science.gov (United States)

    Cason, Zelma; Wilson, Gerri; Golanov, Olga; Tucci, Michelle; McGuire, Robert; Benghuzzi, Hamed

    2012-01-01

    Several investigations have documented that sustained delivery of estrogen can modulate or sustain normal female reproductive functions. However, the literature is lacking scientific evidence regarding the mechanism of estrogen and neuropeptide Y antagonist (NPY) effect on the hypothalamic-pituitary-gonadal axis. The objective of this study was to explore the role of sustained delivery of estrogen and its effects on reproductive unction compared to an antagonist such as NPY. A total of twenty adult female rats (OVX, n=15; intact control, n=5) were divided into five groups (intact control, OVX, sham, OVX + estrogen, and OVX + NPY). Animals in two groups were surgically implanted with a TCP delivery device loaded with estrogen or NPY. Vaginal smears and body weights (BW) were evaluated at baseline and at two weeks post implantation. At the end of two weeks, all animals were euthanized and vital and reproductive organs were retrieved for histopathological evaluation. The results revealed differences in BW between intact control and OVX animals. Furthermore, there was statistical difference (P<0.05) in BW between OVX and OVX + NPY animals. Vaginal smear evaluation revealed that estrogen exposure induced estrus cyclic activities as compared to OVX and sham animals. The animals exposed to sustained delivery of NPY triggered moderate cyclic activities compared to intact control animals. There were no significant differences (P<0.5) in vital organ wet weights among and between animals in all groups. Overall this study proved the capability of TCP to release estrogen and NPY at sustained levels, which resulted inpathophysiological changes in female reproductive organs.

  6. Effects of Vitex agnus-castus fruit on sex hormones and antioxidant indices in a d-galactose-induced aging female mouse model.

    Science.gov (United States)

    Ahangarpour, Akram; Najimi, Seyedeh Asma; Farbood, Yaghoob

    2016-11-01

    Aging is associated with the loss of endocrine function. In this study, Vitex agnus-castus (Vitex), which has antioxidant effects and high levels of phytoestrogen, was investigated with regard to the hypothalamic-pituitary-gonadal axis and antioxidant indices in natural aging and in a d-galactose induced aging model in female mice. The mice were subcutaneously injected with d-galactose (500 mg/kg/d for 45 days). Extract of Vitex (600 mg/kg/bid for 7 days by gavage) was used to treat d-galactose-induced aging and natural aging in mice. Seventy-two female NMRI mice (48 3-month-old normal mice and 24 18-24-month-old mice), weighing 30-35 g were randomly divided into six groups: control, Vitex, d-galactose, Vitex + d-galactose, Aging, and Vitex + Aging. The antioxidant indices and sex hormone levels were subsequently measured by enzyme-linked immunosorbent assay kits. Body weight and the levels of malondialdehyde (MDA), follicle-stimulating hormone, and luteinizing hormone levels were significantly increased in the d-galactose aging and natural aging groups, whereas catalase and superoxide dismutase (SOD) activity and estrogen level were significantly decreased in these same groups. d-Galactose can also disrupt the estrous cycle and damage the uterus and ovarian tissues. Vitex could effectively attenuate these alterations. Vitex improved some aging events in the reproductive system of female mice. Therefore, because of its apparent antiaging effects, Vitex can be suitable for some aging problems such as oxidative stress, female sex hormone deficiency, and an atrophic endometrium. Copyright © 2016. Published by Elsevier Taiwan LLC.

  7. CCDC141 Mutations in Idiopathic Hypogonadotropic Hypogonadism.

    Science.gov (United States)

    Turan, Ihsan; Hutchins, B Ian; Hacihamdioglu, Bulent; Kotan, L Damla; Gurbuz, Fatih; Ulubay, Ayca; Mengen, Eda; Yuksel, Bilgin; Wray, Susan; Topaloglu, A Kemal

    2017-06-01

    Gonadotropin-releasing hormone neurons originate outside the central nervous system in the olfactory placode and migrate into the central nervous system, becoming integral components of the hypothalamic-pituitary-gonadal axis. Failure of this migration can lead to idiopathic hypogonadotropic hypogonadism (IHH)/Kallmann syndrome (KS). We have previously shown that CCDC141 knockdown leads to impaired migration of GnRH neurons but not of olfactory receptor neurons. The aim of this study was to further describe the phenotype and prevalence of CCDC141 mutations in IHH/KS. Using autozygosity mapping, candidate gene screening, whole-exome sequencing, and Sanger sequencing, those individuals carrying deleterious CDCD141 variants and their phenotypes were determined in a cohort of 120 IHH/KS families. No interventions were made. Our studies revealed nine affected individuals from four independent families in which IHH/KS is associated with inactivating CCDC141 variants, revealing a prevalence of 3.3%. Affected individuals (with the exception of those from family 1 who concomitantly have FEZF1 mutations) have normal olfactory function and anatomically normal olfactory bulbs. Four affected individuals show evidence of clinical reversibility. In three of the families, there was at least one more potentially deleterious variant in other known puberty genes with evidence of allelic heterogeneity within respective pedigrees. These studies confirm that inactivating CCDC141 variants cause normosmic IHH but not KS. This is consistent with our previous in vitro experiments showing exclusively impaired embryonic migration of GnRH neurons upon CCDC141 knockdown. These studies expand the clinical and genetic spectrum of IHH and also attest to the complexity of phenotype and genotype in IHH. Copyright © 2017 by the Endocrine Society

  8. GnRH receptor gene mutations in adolescents and young adults presenting with signs of partial gonadotropin deficiency.

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    Johanna Hietamäki

    Full Text Available Biallelic, partial loss-of-function mutations in GNRHR cause a wide spectrum of reproductive phenotypes from constitutional delay of growth and puberty to complete congenital hypogonadotropic hypogonadism. We studied the frequency of GNRHR, FGFR1, TAC3, and TACR3 mutations in nine adolescent and young adult females with clinical cues consistent with partial gonadotropin deficiency (stalled puberty, unexplained secondary amenorrhea, and describe phenotypic features and molecular genetic findings of monozygotic twin brothers with stalled puberty. Two girls out of nine (22%, 95%CI 6-55% carried biallelic mutations in GNRHR. The girl with compound heterozygous c.317A>G p.(Gln106Arg and c.924_926delCTT p.(Phe309del GNRHR mutations displayed incomplete puberty and clinical signs of hypoestrogenism. The patient carrying a homozygous c.785G>A p.(Arg262Gln mutation presented with signs of hypoestrogenism and unexplained secondary amenorrhea. None of the patients exhibited mutations in FGFR1, TAC3, or TACR3. The twin brothers, compound heterozygous for GNRHR mutations c.317A>G p.(Gln106Arg and c.785G>A p.(Arg262Gln, presented with stalled puberty and were discordant for weight, and the heavier of them had lower testosterone levels. These results suggest that genetic testing of the GNRHR gene should be offered to adolescent females with low-normal gonadotropins and unexplained stalled puberty or menstrual dysfunction. In male patients with partial gonadotropin deficiency, excess adipose tissue may suppress hypothalamic-pituitary-gonadal axis.

  9. GPR54 regulates ERK1/2 activity and hypothalamic gene expression in a Gα(q/11 and β-arrestin-dependent manner.

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    Jacob M Szereszewski

    Full Text Available G protein-coupled receptor 54 (GPR54 is a G(q/11-coupled 7 transmembrane-spanning receptor (7TMR. Activation of GPR54 by kisspeptin (Kp stimulates PIP(2 hydrolysis, Ca(2+ mobilization and ERK1/2 MAPK phosphorylation. Kp and GPR54 are established regulators of the hypothalamic-pituitary-gonadal (HPG axis and loss-of-function mutations in GPR54 are associated with an absence of puberty and hypogonadotropic hypogonadism, thus defining an important role of the Kp/GPR54 signaling system in reproductive function. Given the tremendous physiological and clinical importance of the Kp/GPR54 signaling system, we explored the contributions of the GPR54-coupled G(q/11 and β-arrestin pathways on the activation of a major downstream signaling molecule, ERK, using G(q/11 and β-arrestin knockout mouse embryonic fibroblasts. Our study revealed that GPR54 employs the G(q/11 and β-arrestin-2 pathways in a co-dependent and temporally overlapping manner to positively regulate ERK activity and pERK nuclear localization. We also show that while β-arrestin-2 potentiates GPR54 signaling to ERK, β-arrestin-1 inhibits it. Our data also revealed that diminished β-arrestin-1 and -2 expression in the GT1-7 GnRH hypothalamic neuronal cell line triggered distinct patterns of gene expression following Kp-10 treatment. Thus, β-arrestin-1 and -2 also regulate distinct downstream responses in gene expression. Finally, we showed that GPR54, when uncoupled from the G(q/11 pathway, as is the case for several naturally occurring GPR54 mutants associated with hypogonadotropic hypogonadism, continues to regulate gene expression in a G protein-independent manner. These new and exciting findings add significantly to our mechanistic understanding of how this important receptor signals intracellularly in response to kisspeptin stimulation.

  10. Differential protein expression profile in the hypothalamic GT1-7 cell line after exposure to anabolic androgenic steroids.

    Directory of Open Access Journals (Sweden)

    Freddyson J Martínez-Rivera

    Full Text Available The abuse of anabolic androgenic steroids (AAS has been considered a major public health problem during decades. Supraphysiological doses of AAS may lead to a variety of neuroendocrine problems. Precisely, the hypothalamic-pituitary-gonadal (HPG axis is one of the body systems that is mainly influenced by steroidal hormones. Fluctuations of the hormonal milieu result in alterations of reproductive function, which are made through changes in hypothalamic neurons expressing gonadotropin-releasing hormone (GnRH. In fact, previous studies have shown that AAS modulate the activity of these neurons through steroid-sensitive afferents. To increase knowledge about the cellular mechanisms induced by AAS in GnRH neurons, we performed proteomic analyses of the murine hypothalamic GT1-7 cell line after exposure to 17α-methyltestosterone (17α-meT; 1 μM. These cells represent a good model for studying regulatory processes because they exhibit the typical characteristics of GnRH neurons, and respond to compounds that modulate GnRH in vivo. Two-dimensional difference in gel electrophoresis (2D-DIGE and mass spectrometry analyses identified a total of 17 different proteins that were significantly affected by supraphysiological levels of AAS. Furthermore, pathway analyses showed that modulated proteins were mainly associated to glucose metabolism, drug detoxification, stress response and cell cycle. Validation of many of these proteins, such as GSTM1, ERH, GAPDH, PEBP1 and PDIA6, were confirmed by western blotting. We further demonstrated that AAS exposure decreased expression of estrogen receptors and GnRH, while two important signaling pathway proteins p-ERK, and p-p38, were modulated. Our results suggest that steroids have the capacity to directly affect the neuroendocrine system by modulating key cellular processes for the control of reproductive function.

  11. Treatment of Anabolic-Androgenic Steroid Dependence: Emerging Evidence and Its Implications

    Science.gov (United States)

    Kanayama, Gen; Brower, Kirk J.; Wood, Ruth I.; Hudson, James I.; Pope, Harrison G.

    2010-01-01

    Currently, few users of anabolic-androgenic steroids (AAS) seek substance-abuse treatment. But this picture may soon change substantially, because illicit AAS use did not become widespread until the 1980s, and consequently the older members of this AAS-using population—those who initiated AAS as youths in the 1980s—are only now reaching middle age. Members of this group, especially those who have developed AAS dependence, may therefore be entering the age of risk for cardiac and psychoneuroendocrine complications sufficient to motivate them for substance-abuse treatment. We suggest that this treatment should address at least three etiologic mechanisms by which AAS dependence might develop. First, individuals with body-image disorders such as “muscle dysmorphia” may become dependent on AAS for their anabolic effects; these body-image disorders may respond to psychological therapies or pharmacologic treatments. Second, AAS suppress the male hypothalamic-pituitary-gonadal axis via their androgenic effects, potentially causing hypogonadism during AAS withdrawal. Men experiencing prolonged dysphoric effects or frank major depression from hypogonadism may desire to resume AAS, thus contributing to AAS dependence. AAS-induced hypogonadism may require treatment with human chorionic gonadotropin or clomiphene to reactivate neuroendocrine function, and may necessitate antidepressant treatments in cases of depression inadequately responsive to endocrine therapies alone. Third, human and animal evidence indicates that AAS also possess hedonic effects, which likely promote dependence via mechanisms shared with classical addictive drugs, especially opioids. Indeed, the opioid antagonist naltrexone blocks AAS dependence in animals. By inference, pharmacological and psychosocial treatments for human opioid dependence might also benefit AAS-dependent individuals. PMID:20188494

  12. Nandrolone effects on men’s semen parameters in Erbil city

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    Abdalmuhaimn Y. Sharef

    2017-08-01

    Full Text Available Background and objective: Anabolic androgenic steroids are synthetic compounds based on the structure of testosterone, and are used to treat various conditions such as reproductive system dysfunction. High doses of anabolic androgenic steroids and exercise influence the hypothalamic pituitary gonadal axis, which can, in turn, affect testicular apoptosis. This study aimed to investigate the influence of anabolic androgenic steroids on semen parameters in bodybuilders (heavy exercise in Erbil city. Methods: Semen specimens and serum were collected from 150 which divided into three groups; each consists of 50 men. The control group (A didn't practice exercise so didn't receive nandrolone. The exercise group (B who practice daily without taking nandrolone. The exercise and treated group (C who practice exercise and had been using nandrolone (200 mg- wk-1, intramuscularly for at least three months. Smear prepared by methyline blue stain and assessment of semen volume, sperm morphology, sperm concentration ,motility were carried out .Serum levels of follicle-stimulating hormone, luteinizing hormone, and testosterone were also carried out. Results: There was no difference in the semen volume within three groups. Sperm concentration and the percentage of sperm motility in the group C was significantly lower (P <0.001 than that in the other groups. A significantly increased percentage of sperm with the tapered head was found in the group C. Our results also demonstrated a significant decrease in testosterone and follicle-stimulating hormone in the group C compared to group A and B. Conclusion: Users of anabolic-androgenic steroids have sperm with abnormal shape, especially tapered head, and low concentration of sperm with sluggish motility attributing to infertility.

  13. Transcription of key genes regulating gonadal steroidogenesis in control and ketoconazole- or vinclozolin-exposed fathead minnows

    Energy Technology Data Exchange (ETDEWEB)

    Villeneuve, Daniel L.; Blake, Lindsey S.; Brodin, Jeffrey; Greene, Katie J.; Knoebl, Iris; Miracle, Ann L.; Martinovic, Dalma; Ankley, Gerald T.

    2007-08-01

    This study evaluated changes in the expression of steroidogenesis-related genes in male fathead minnows exposed to ketoconazole (KTC) or vinclozolin (VZ) for 21 days. The aim was to evaluate links between molecular changes and higher level outcomes after exposure to endocrine-active chemicals (EACs) with different modes of action. To aid our analysis and interpretation of EAC-related effects, we first examined variation in the relative abundance of steroidogenesis-related gene transcripts in the gonads of male and female fathead minnows as a function of age, gonad development, and spawning status, independent of EAC exposure. Gonadal expression of several genes varied with age and/or gonadal somatic index in either males or females. However, with the exception of aromatase, steroidogenesis-related gene expression did not vary with spawning status. Following the baseline experiments, expression of the selected genes in male fathead minnows exposed to KTC or VZ was evaluated in the context of effects observed at higher levels of organization. Exposure to KTC elicited changes in gene transcription that were consistent with an apparent compensatory response to the chemical's anticipated direct inhibition of steroidogenic enzyme activity. Exposure to VZ, an antiandrogen expected to indirectly impact steroidogenesis, increased pituitary expression of follicle-stimulating hormone beta-subunit as well as testis expression of 20beta-hydroxysteroid dehydrogenase and luteinizing hormone receptor transcripts. Results of this study contribute to ongoing research aimed at understanding responses of the teleost hypothalamic-pituitary-gonadal axis to different types of EACs and how changes in molecular endpoints translate into apical outcomes reflective of either adverse effect or compensation.

  14. Hypogonadotropic Hypogonadism in Males with Glycogen Storage Disease Type 1.

    Science.gov (United States)

    Wong, Evelyn M; Lehman, Anna; Acott, Philip; Gillis, Jane; Metzger, Daniel L; Sirrs, Sandra

    2017-01-01

    Glycogen storage disease type 1 is an autosomal recessive disorder with an incidence of 1 in 100,000. Long-term complications include chronic blood glucose lability, lactic academia, short stature, osteoporosis, delayed puberty, gout, progressive renal insufficiency, systemic or pulmonary hypertension, hepatic adenomas at risk for malignant transformation, anemia, vitamin D deficiency, hyperuricemic nephrocalcinosis, inflammatory bowel syndrome (type 1b), hypertriglyceridemia, and irregular menstrual cycles. We describe hypogonadotropic hypogonadism as a novel complication in glycogen storage disease (GSD) type 1. Case Studies and Methods: Four unrelated patients with GSD 1a (N = 1) and 1b (N = 3) were found to have hypogonadotropic hypogonadism diagnosed at different ages. Institutional Research Ethics Board approval was obtained as appropriate. Participant consent was obtained. A retrospective chart review was performed and clinical symptoms and results of investigations summarized as a case series. All patients were confirmed biochemically to have low luteinizing hormone (LH) and follicular stimulating hormone (FSH), and correspondingly low total testosterone. Clinical symptoms of hypogonadism varied widely. Investigations for other causes of hypogonadotropic hypogonadism were unremarkable. In addition, all patients were found to have disproportionately low bone mineral density at the lumbar spine compared to the hip. Common to all patients was erratic metabolic control, including recurrent hypoglycemia and elevated lactate levels. Recurrent elevations in cortisol in response to hypoglycemia may be the underlying pathology leading to suppression of gonadotropin-releasing hormone (GnRH) release. Incorporating clinical and/or biochemical screening of the hypothalamic-pituitary-gonadal axis may be important in the management of this disease. Testosterone therapy however needs to be carefully considered because of the risk of hepatic adenomas.

  15. An anti-steroidogenic inhibitory primer pheromone in male sea lamprey (Petromyzon marinus)

    Science.gov (United States)

    Chung-Davidson, Yu-Wen; Wang, Huiyong; Bryan, Mara B.; Wu, Hong; Johnson, Nicholas S.; Li, Weiming

    2013-01-01

    Reproductive functions can be modulated by both stimulatory and inhibitory primer pheromones released by conspecifics. Many stimulatory primer pheromones have been documented, but relatively few inhibitory primer pheromones have been reported in vertebrates. The sea lamprey male sex pheromone system presents an advantageous model to explore the stimulatory and inhibitory primer pheromone functions in vertebrates since several pheromone components have been identified. We hypothesized that a candidate sex pheromone component, 7α, 12α-dihydroxy-5α-cholan-3-one-24-oic acid (3 keto-allocholic acid or 3kACA), exerts priming effects through the hypothalamic-pituitary-gonadal (HPG) axis. To test this hypothesis, we measured the peptide concentrations and gene expressions of lamprey gonadotropin releasing hormones (lGnRH) and the HPG output in immature male sea lamprey exposed to waterborne 3kACA. Exposure to waterborne 3kACA altered neuronal activation markers such as jun and jun N-terminal kinase (JNK), and lGnRH mRNA levels in the brain. Waterborne 3kACA also increased lGnRH-III, but not lGnRH-I or -II, in the forebrain. In the plasma, 3kACA exposure decreased all three lGnRH peptide concentrations after 1 h exposure. After 2 h exposure, 3kACA increased lGnRHI and -III, but decreased lGnRH-II peptide concentrations in the plasma. Plasma lGnRH peptide concentrations showed differential phasic patterns. Group housing condition appeared to increase the averaged plasma lGnRH levels in male sea lamprey compared to isolated males. Interestingly, 15α-hydroxyprogesterone (15α-P) concentrations decreased after prolonged 3kACA exposure (at least 24 h). To our knowledge, this is the only known synthetic vertebrate pheromone component that inhibits steroidogenesis in males.

  16. The presence of symptoms of testosterone deficiency in the exercise-hypogonadal male condition and the role of nutrition.

    Science.gov (United States)

    Hooper, David R; Kraemer, William J; Saenz, Catherine; Schill, Kevin E; Focht, Brian C; Volek, Jeff S; Maresh, Carl M

    2017-07-01

    High volumes of aerobic exercise have been associated with reduced testosterone (T), known as the exercise-hypogonadal male condition (EHMC). Although the presence of low T has been identified, few studies have assessed the presence of androgen-deficient symptoms. The purpose of this investigation is to assess men exhibiting EHMC and evaluate their hypothalamic-pituitary-gonadal axis, the presence of hypogonadal symptoms, and also investigate a possible contribution of inadequate nutrition to the condition. A cross-sectional design compared 9 long-distance runners exhibiting EHMC to 8 non-active controls. Comparisons included serum T, luteinizing hormone (LH), follicle-stimulating hormone, and cortisol, the Aging Male Symptoms (AMS) questionnaire score, bone mineral density (BMD), and a food frequency questionnaire. Mean T was significantly reduced in the EHMC group (EHMC 9.2 nmol L -1 vs. CONT 16.2 nmol L -1 ). The EHMC group demonstrated significantly higher AMS scores (EHMC 27.1 ± 7.3 vs. CONT 19.7 ± 2.5). There were no differences in bone density, although 3 cases of osteopenia were noted for EHMC in the lumbar spine, 1 in the right femur, and 1 in the radius. Energy availability was significantly reduced in EHMC (EHMC 27.2 ± 12.7 vs. CONT 45.4 ± 18.2 kcal d FFM -1 ). Men exhibiting EHMC do appear to present with symptoms associated with androgen deficiency. For the most part, these symptoms are limited to those reported on the AMS questionnaire, although there are also some cases of clinically low BMD. It is possible that inadequate energy intake is contributing to this condition.

  17. Results of a Second Year of Therapy with the 12-Month Histrelin Implant for the Treatment of Central Precocious Puberty

    Directory of Open Access Journals (Sweden)

    Samar Rahhal

    2009-01-01

    Full Text Available Background. Gonadotropin releasing hormone analogs (GnRHas are standard of care for central precocious puberty (CPP. The histrelin subcutaneous implant is safe and effective in the treatment of CPP for one year. Objective. The study evaluates a second year of therapy in children with CPP who received a new implant after one year of treatment. Methods. A prospective one-year study following an initial 12-month treatment period was conducted. Results. Thirty-one patients (29 girls aged 7.7±1.5 years received a second implant. Eighteen were naïve to GnRHa therapy at first implantation. Peak LH declined from 0.92±0.58 mIU/mL at 12 months to 0.51±0.33 mIU/mL at 24 months (P < .0001 in naïve subjects, and from 0.74±0.50 mIU/mL at 12 months to 0.45±0.35 mIU/mL at 24 months (P=.0081 in previously treated subjects. Predicted adult height increased by 5.1 cm at 24 months (P=.0001. Minor implant site reactions occurred in 61%, while minor difficulties with explantation occurred in 32.2% of subjects. Conclusion. The histrelin implant demonstrates profound hypothalamic-pituitary-gonadal axis suppression when a new implant is placed for a second year of treatment. Prospective follow-up of this therapeutic modality for the treatment of CPP is needed.

  18. Reversal and Relapse of Hypogonadotropic Hypogonadism: Resilience and Fragility of the Reproductive Neuroendocrine System

    Science.gov (United States)

    Sidhoum, Valerie F.; Chan, Yee-Ming; Lippincott, Margaret F.; Balasubramanian, Ravikumar; Quinton, Richard; Plummer, Lacey; Dwyer, Andrew; Pitteloud, Nelly; Hayes, Frances J.; Hall, Janet E.; Martin, Kathryn A.; Boepple, Paul A.

    2014-01-01

    Context: A subset of patients diagnosed with idiopathic hypogonadotropic hypogonadism (IHH) later achieves activation of their hypothalamic-pituitary-gonadal axis with normalization of steroidogenesis and/or gametogenesis, a phenomenon termed reversal. Objective: The objective of this study was to determine the natural history of reversal and to identify associated phenotypes and genotypes. Design, Setting, and Subjects: This was a retrospective review of clinical, biochemical, and genetic features of patients with IHH evaluated at an academic medical center. Main Outcome Measures: History of spontaneous fertility, regular menses, testicular growth, or normalization of serum sex steroids, LH secretory profiles, brain imaging findings, and sequences of 14 genes associated with IHH were reviewed. Results: Of 308 patients with IHH, 44 underwent reversal. Time-to-event analysis estimated a lifetime incidence of reversal of 22%. There were no differences in the rates of cryptorchidism, micropenis, or partial pubertal development in patients with reversal vs IHH patients without reversal. Fifteen patients with reversal (30%) had Kallmann syndrome (IHH and anosmia); one had undetectable olfactory bulbs on a brain magnetic resonance imaging scan. Subjects with reversal were enriched for mutations affecting neurokinin B signaling compared with a cohort of IHH patients without reversal (10% vs 3%, P = .044), had comparable frequencies of mutations in FGFR1, PROKR2, and GNRHR, and had no mutations in KAL1. Five men did not sustain their reversal and again developed hypogonadotropism. Conclusions: Reversal of IHH may be more widespread than previously appreciated and occurs across a broad range of genotypes and phenotypes. Enrichment for mutations that disrupt neurokinin B signaling in patients who reversed indicates that, despite the importance of this signaling pathway for normal pubertal timing, its function is dispensable later in life. The occurrence of reversal in a

  19. Treatment of anabolic-androgenic steroid dependence: Emerging evidence and its implications.

    Science.gov (United States)

    Kanayama, Gen; Brower, Kirk J; Wood, Ruth I; Hudson, James I; Pope, Harrison G

    2010-06-01

    Currently, few users of anabolic-androgenic steroids (AAS) seek substance abuse treatment. But this picture may soon change substantially, because illicit AAS use did not become widespread until the 1980s, and consequently the older members of this AAS-using population - those who initiated AAS as youths in the 1980s - are only now reaching middle age. Members of this group, especially those who have developed AAS dependence, may therefore be entering the age of risk for cardiac and psychoneuroendocrine complications sufficient to motivate them for substance abuse treatment. We suggest that this treatment should address at least three etiologic mechanisms by which AAS dependence might develop. First, individuals with body image disorders such as "muscle dysmorphia" may become dependent on AAS for their anabolic effects; these body image disorders may respond to psychological therapies or pharmacological treatments. Second, AAS suppress the male hypothalamic-pituitary-gonadal axis via their androgenic effects, potentially causing hypogonadism during AAS withdrawal. Men experiencing prolonged dysphoric effects or frank major depression from hypogonadism may desire to resume AAS, thus contributing to AAS dependence. AAS-induced hypogonadism may require treatment with human chorionic gonadotropin or clomiphene to reactivate neuroendocrine function, and may necessitate antidepressant treatments in cases of depression inadequately responsive to endocrine therapies alone. Third, human and animal evidence indicates that AAS also possess hedonic effects, which likely promote dependence via mechanisms shared with classical addictive drugs, especially opioids. Indeed, the opioid antagonist naltrexone blocks AAS dependence in animals. By inference, pharmacological and psychosocial treatments for human opioid dependence might also benefit AAS-dependent individuals. Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.

  20. Male patients with terminal renal failure exhibit low serum levels of antimüllerian hormone

    Directory of Open Access Journals (Sweden)

    Dag Eckersten

    2015-02-01

    Full Text Available Male reproductive function is impaired during end-stage renal disease (ESRD. Disturbance of the hypothalamic-pituitary-gonadal axis, and therefore the regulation of sex hormones, is one of the major causes. Our focus was to include antimüllerian hormone (AMH and inhibin B concentrations. Twenty male patients on hemodialysis, median age 40 (26-48 years, were analyzed for follicle-stimulating hormone (FSH, luteinizing hormone (LH, prolactin, sex hormone-binding globulin (SHBG, testosterone, estradiol, AMH and inhibin B levels. We used 144 proven fertile men, median age 32 (19-44 years as a control group and analyzed differences using multiple linear regression. Males with ESRD demonstrated higher mean values for prolactin, 742 versus normal 210 mIE l−1 (95% confidence interval (CI: 60.3, 729, LH, 8.87 versus normal 4.5 IE l−1 (95% CI: 2.75, 6.14, and estradiol 89.7 versus normal 79.0 pmol l−1 (95% CI: −1.31, −0.15. Mean value for AMH was lower, 19.5 versus normal 47.3 pmol l−1 (95% CI: −37.6, −11.6. There were no differences found for FSH, SHBG, inhibin B and testosterone. The most important difference was found for AMH, a marker of Sertoli cell function in the testes, which decreased by close to 60% when compared with controls. Combined with an increase in LH, these findings may indicate a dysfunction of Sertoli cells and an effect on Leydig cells contributing to a potential mechanism of reproductive dysfunction in men with ESRD.

  1. Diamond Machining of an Off-Axis Biconic Aspherical Mirror

    Science.gov (United States)

    Ohl, Raymond G.; Preuss, Werner; Sohn, Alex; MacKenty, John

    2009-01-01

    Two diamond-machining methods have been developed as part of an effort to design and fabricate an off-axis, biconic ellipsoidal, concave aluminum mirror for an infrared spectrometer at the Kitt Peak National Observatory. Beyond this initial application, the methods can be expected to enable satisfaction of requirements for future instrument mirrors having increasingly complex (including asymmetrical), precise shapes that, heretofore, could not readily be fabricated by diamond machining or, in some cases, could not be fabricated at all. In the initial application, the mirror is prescribed, in terms of Cartesian coordinates x and y, by aperture dimensions of 94 by 76 mm, placements of -2 mm off axis in x and 227 mm off axis in y, an x radius of curvature of 377 mm, a y radius of curvature of 407 mm, an x conic constant of 0.078, and a y conic constant of 0.127. The aspect ratio of the mirror blank is about 6. One common, "diamond machining" process uses single-point diamond turning (SPDT). However, it is impossible to generate the required off-axis, biconic ellipsoidal shape by conventional SPDT because (1) rotational symmetry is an essential element of conventional SPDT and (2) the present off-axis biconic mirror shape lacks rotational symmetry. Following conventional practice, it would be necessary to make this mirror from a glass blank by computer-controlled polishing, which costs more than diamond machining and yields a mirror that is more difficult to mount to a metal bench. One of the two present diamond machining methods involves the use of an SPDT machine equipped with a fast tool servo (FTS). The SPDT machine is programmed to follow the rotationally symmetric asphere that best fits the desired off-axis, biconic ellipsoidal surface. The FTS is actuated in synchronism with the rotation of the SPDT machine to generate the difference between the desired surface and the best-fit rotationally symmetric asphere. In order to minimize the required stroke of the FTS

  2. Gut/brain axis and the microbiota.

    Science.gov (United States)

    Mayer, Emeran A; Tillisch, Kirsten; Gupta, Arpana

    2015-03-02

    Tremendous progress has been made in characterizing the bidirectional interactions between the central nervous system, the enteric nervous system, and the gastrointestinal tract. A series of provocative preclinical studies have suggested a prominent role for the gut microbiota in these gut-brain interactions. Based on studies using rodents raised in a germ-free environment, the gut microbiota appears to influence the development of emotional behavior, stress- and pain-modulation systems, and brain neurotransmitter systems. Additionally, microbiota perturbations by probiotics and antibiotics exert modulatory effects on some of these measures in adult animals. Current evidence suggests that multiple mechanisms, including endocrine and neurocrine pathways, may be involved in gut microbiota-to-brain signaling and that the brain can in turn alter microbial composition and behavior via the autonomic nervous system. Limited information is available on how these findings may translate to healthy humans or to disease states involving the brain or the gut/brain axis. Future research needs to focus on confirming that the rodent findings are translatable to human physiology and to diseases such as irritable bowel syndrome, autism, anxiety, depression, and Parkinson's disease.

  3. Principles of the prolactin/vasoinhibin axis.

    Science.gov (United States)

    Triebel, Jakob; Bertsch, Thomas; Bollheimer, Cornelius; Rios-Barrera, Daniel; Pearce, Christy F; Hüfner, Michael; Martínez de la Escalera, Gonzalo; Clapp, Carmen

    2015-11-15

    The hormonal family of vasoinhibins, which derive from the anterior pituitary hormone prolactin, are known for their inhibiting effects on blood vessel growth, vasopermeability, and vasodilation. As pleiotropic hormones, vasoinhibins act in multiple target organs and tissues. The generation, secretion, and regulation of vasoinhibins are embedded into the organizational principle of an axis, which integrates the hypothalamus, the pituitary, and the target tissue microenvironment. This axis is designated as the prolactin/vasoinhibin axis. Disturbances of the prolactin/vasoinhibin axis are associated with the pathogenesis of retinal and cardiac diseases and with diseases occurring during pregnancy. New phylogenetical, physiological, and clinical implications are discussed. Copyright © 2015 the American Physiological Society.

  4. Acute injuries of the axis vertebra

    Energy Technology Data Exchange (ETDEWEB)

    Burke, J.T. (United General Hospital, Sedro Woolley, WA (USA)); Harris, J.H. (Texas Univ., Houston, TX (USA). Dept. of Radiology)

    1989-08-01

    A retrospective analysis of 165 patients admitted to Hermann Hospital with acute injuries of the axis vertebra revealed 68 (41%) dens fractures, 62 (38%) cases of traumatic spondylolisthesis ('hangman's' fracture), 21 (13%) extension teardrop fractures, 10 (6%) hyperextension dislocations, and 2 (1.0%) fractures each of the laminae and spinous processes. Of the axis injuries 31 (18%) were limited to the axis body alone. Of these, 21 (61%) were hyperextension teardrop fractures and 10 (32%) were hyperextension dislocations. Axis injuries were associated with acute injuries of other cervical vertebrae in 14 (8%) of the patients. (orig./GDG).

  5. Design of Off-Axis PIAACMC Mirrors

    Science.gov (United States)

    Pluzhnik, Eugene; Guyon, Olivier; Belikov, Ruslan; Kern, Brian; Bendek, Eduardo

    2015-01-01

    The Phase-Induced Amplitude Apodization Complex Mask Coronagraph (PIAACMC) provides an efficient way to control diffraction propagation effects caused by the central obstruction/segmented mirrors of the telescope. PIAACMC can be optimized in a way that takes into account both chromatic diffraction effects caused by the telescope obstructed aperture and tip/tilt sensitivity of the coronagraph. As a result, unlike classic PIAA, the PIAACMC mirror shapes are often slightly asymmetric even for an on-axis configuration and require more care in calculating off-axis shapes when an off-axis configuration is preferred. A method to design off-axis PIAA mirror shapes given an on-axis mirror design is presented. The algorithm is based on geometrical ray tracing and is able to calculate off-axis PIAA mirror shapes for an arbitrary geometry of the input and output beams. The method is demonstrated using the third generation PIAACMC design for WFIRST-AFTA (Wide Field Infrared Survey Telescope-Astrophysics Focused Telescope Assets) telescope. Geometrical optics design issues related to the off-axis diffraction propagation effects are also discussed.

  6. Neuropeptides and the microbiota-gut-brain axis.

    Science.gov (United States)

    Holzer, Peter; Farzi, Aitak

    2014-01-01

    Neuropeptides are important mediators both within the nervous system and between neurons and other cell types. Neuropeptides such as substance P, calcitonin gene-related peptide and neuropeptide Y (NPY), vasoactive intestinal polypeptide, somatostatin and corticotropin-releasing factor are also likely to play a role in the bidirectional gut-brain communication. In this capacity they may influence the activity of the gastrointestinal microbiota and its interaction with the gut-brain axis. Current efforts in elucidating the implication of neuropeptides in the microbiota-gut-brain axis address four information carriers from the gut to the brain (vagal and spinal afferent neurons; immune mediators such as cytokines; gut hormones; gut microbiota-derived signalling molecules) and four information carriers from the central nervous system to the gut (sympathetic efferent neurons; parasympathetic efferent neurons; neuroendocrine factors involving the adrenal medulla; neuroendocrine factors involving the adrenal cortex). Apart from operating as neurotransmitters, many biologically active peptides also function as gut hormones. Given that neuropeptides and gut hormones target the same cell membrane receptors (typically G protein-coupled receptors), the two messenger roles often converge in the same or similar biological implications. This is exemplified by NPY and peptide YY (PYY), two members of the PP-fold peptide family. While PYY is almost exclusively expressed by enteroendocrine cells, NPY is found at all levels of the gut-brain and brain-gut axis. The function of PYY-releasing enteroendocrine cells is directly influenced by short chain fatty acids generated by the intestinal microbiota from indigestible fibre, while NPY may control the impact of the gut microbiota on inflammatory processes, pain, brain function and behaviour. Although the impact of neuropeptides on the interaction between the gut microbiota and brain awaits to be analysed, biologically active peptides

  7. A high speed vertical axis wind machine

    National Research Council Canada - National Science Library

    South, P

    1976-01-01

    The operational feasibility of vertical axis wind machines was investigated at the National Aeronautical Establishment in Ottawa through use of a wind tunnel and a rotor with blades curved in a skipping rope shape...

  8. UMAPRM: Uniformly sampling the medial axis

    KAUST Repository

    Yeh, Hsin-Yi Cindy

    2014-05-01

    © 2014 IEEE. Maintaining clearance, or distance from obstacles, is a vital component of successful motion planning algorithms. Maintaining high clearance often creates safer paths for robots. Contemporary sampling-based planning algorithms That utilize The medial axis, or The set of all points equidistant To Two or more obstacles, produce higher clearance paths. However, They are biased heavily Toward certain portions of The medial axis, sometimes ignoring parts critical To planning, e.g., specific Types of narrow passages. We introduce Uniform Medial Axis Probabilistic RoadMap (UMAPRM), a novel planning variant That generates samples uniformly on The medial axis of The free portion of Cspace. We Theoretically analyze The distribution generated by UMAPRM and show its uniformity. Our results show That UMAPRM\\'s distribution of samples along The medial axis is not only uniform but also preferable To other medial axis samplers in certain planning problems. We demonstrate That UMAPRM has negligible computational overhead over other sampling Techniques and can solve problems The others could not, e.g., a bug Trap. Finally, we demonstrate UMAPRM successfully generates higher clearance paths in The examples.

  9. Craniospinal axis irradiation: an improved electron technique for irradiation of the spinal axis

    International Nuclear Information System (INIS)

    Chun Li; Vijayakumar, S.; Myrianthopoulos, L.C.; Kuchnir, F.T.; Muller-Runkel, R.

    1994-01-01

    The authors review dosimetric features of craniospinal axis irradiation in the areas of matching cranial and spinal fields, with reference to normal structures within the spinal field. The implications of the use of photon or electron modalities for the spinal port were evaluated. A novel method of matching the cranial photon and the spinal electron fields involving a computer-aided junction design is presented, involving moving the photon beam in three steps to degrade its penumbra to match that of the electron field. Thermoluminescent dosimetry in a Rando phantom and computed tomography-based dose-volume histogram study for an illustrative paediatric case were used to compare dose to normal structures within the spinal field. Results show that the use of electrons for the spinal field leads to better sparing of deep seated normal structures. For bone marrow, the use of a customized bolus for the spinal field results in an improved dose distribution, making electrons potentially superior to photons for radiobiological reasons. (author)

  10. A Simple Method to Determine the "R" or "S" Configuration of Molecules with an Axis of Chirality

    Science.gov (United States)

    Wang, Cunde; Wu, Weiming

    2011-01-01

    A simple method for the "R" or "S" designation of molecules with an axis of chirality is described. The method involves projection of the substituents along the chiral axis, utilizes the Cahn-Ingold-Prelog sequence rules in assigning priority to the substituents, is easy to use, and has broad applicability. (Contains 5 figures.)

  11. Actuator assembly including a single axis of rotation locking member

    Science.gov (United States)

    Quitmeyer, James N.; Benson, Dwayne M.; Geck, Kellan P.

    2009-12-08

    An actuator assembly including an actuator housing assembly and a single axis of rotation locking member fixedly attached to a portion of the actuator housing assembly and an external mounting structure. The single axis of rotation locking member restricting rotational movement of the actuator housing assembly about at least one axis. The single axis of rotation locking member is coupled at a first end to the actuator housing assembly about a Y axis and at a 90.degree. angle to an X and Z axis providing rotation of the actuator housing assembly about the Y axis. The single axis of rotation locking member is coupled at a second end to a mounting structure, and more particularly a mounting pin, about an X axis and at a 90.degree. angle to a Y and Z axis providing rotation of the actuator housing assembly about the X axis. The actuator assembly is thereby restricted from rotation about the Z axis.

  12. Intestinal barrier function and the brain-gut axis.

    Science.gov (United States)

    Alonso, Carmen; Vicario, María; Pigrau, Marc; Lobo, Beatriz; Santos, Javier

    2014-01-01

    The luminal-mucosal interface of the intestinal tract is the first relevant location where microorganism-derived antigens and all other potentially immunogenic particles face the scrutiny of the powerful mammalian immune system. Upon regular functioning conditions, the intestinal barrier is able to effectively prevent most environmental and external antigens to interact openly with the numerous and versatile elements that compose the mucosal-associated immune system. This evolutionary super system is capable of processing an astonishing amount of antigens and non-immunogenic particles, approximately 100 tons in one individual lifetime, only considering food-derived components. Most important, to develop oral tolerance and proper active immune responses needed to prevent disease and inflammation, this giant immunogenic load has to be managed in a way that physiological inflammatory balance is constantly preserved. Adequate functioning of the intestinal barrier involves local and distant regulatory networks integrating the so-called brain-gut axis. Along this complex axis both brain and gut structures participate in the processing and execution of response signals to external and internal changes coming from the digestive tract, using multidirectional pathways to communicate. Dysfunction of brain-gut axis facilitates malfunctioning of the intestinal barrier, and vice versa, increasing the risk of uncontrolled immunological reactions that may trigger mucosal and brain low-grade inflammation, a putative first step to the initiation of more permanent gut disorders. In this chapter, we describe the structure, function and interactions of intestinal barrier, microbiota and brain-gut axis in both healthy and pathological conditions.

  13. Endocannabinoid Signaling, Glucocorticoid-Mediated Negative Feedback and Regulation of the HPA Axis

    Science.gov (United States)

    Hill, M. N.; Tasker, J. G.

    2012-01-01

    The hypothalamic-pituitary-adrenal (HPA) axis regulates the outflow of glucocorticoid hormones under basal conditions and in response to stress. Within the last decade, a large body of evidence has mounted indicating that the endocannabinoid system is involved in the central regulation of the stress response; however, the specific role endocannabinoid signalling plays in phases of HPA axis regulation, or the neural sites of action mediating this regulation, was not mapped out until recently. This review aims to collapse the current state of knowledge regarding the role of the endocannabinoid system in the regulation of the HPA axis to put together a working model of how and where endocannabinoids act within the brain to regulate outflow of the HPA axis. Specifically, we discuss the role of the endocannabinoid system in the regulation of the HPA axis under basal conditions, activation in response to acute stress and glucocorticoid-mediated negative feedback. Interestingly, there appears to be some anatomical specificity to the role of the endocannabinoid system in each phase of HPA axis regulation, as well as distinct roles of both anandamide and 2-arachidonoylglycerol in these phases. Ultimately, the current level of information indicates that endocannabinoid signalling acts to suppress HPA axis activity through concerted actions within the prefrontal cortex, amygdala and hypothalamus. PMID:22214537

  14. Aeroelastically coupled blades for vertical axis wind turbines

    Science.gov (United States)

    Paquette, Joshua; Barone, Matthew F.

    2016-02-23

    Various technologies described herein pertain to a vertical axis wind turbine blade configured to rotate about a rotation axis. The vertical axis wind turbine blade includes at least an attachment segment, a rear swept segment, and optionally, a forward swept segment. The attachment segment is contiguous with the forward swept segment, and the forward swept segment is contiguous with the rear swept segment. The attachment segment includes a first portion of a centroid axis, the forward swept segment includes a second portion of the centroid axis, and the rear swept segment includes a third portion of the centroid axis. The second portion of the centroid axis is angularly displaced ahead of the first portion of the centroid axis and the third portion of the centroid axis is angularly displaced behind the first portion of the centroid axis in the direction of rotation about the rotation axis.

  15. Theoretical tool movement required to diamond turn an off-axis paraboloid on axis

    International Nuclear Information System (INIS)

    Thompson, D.C.

    1976-01-01

    Current techniques for manufacturing off-axis paraboloids are both expensive and insufficiently accurate. An alternative method, turning the workpiece about its axis on a diamond-turning machine, is presented, and the equations describing the necessary tool movement are derived. A discussion of a particular case suggests that the proposed technique is feasible

  16. Modular off-axis solar concentrator

    Science.gov (United States)

    Plesniak, Adam P; Hall, John C

    2015-01-27

    A solar concentrator including a housing defining a vertical axis and including a receiving wall connected to a reflecting wall to define an internal volume and an opening into the internal volume, wherein the reflecting wall defines at least one primary optical element, and wherein at least a portion of the reflecting wall includes a layer of reflective material, the housing further including a cover connected to the receiving wall and the reflecting wall to seal the opening, and at least one receiver mounted on the receiving wall such that a vertical axis of the receiver is disposed at a non-zero angle relative to the vertical axis of the housing, the receiver including at least one photovoltaic cell.

  17. Enclosed, off-axis solar concentrator

    Science.gov (United States)

    Benitez, Pablo; Grip, Robert E; Minano, Juan C; Narayanan, Authi A; Plesniak, Adam; Schwartz, Joel A

    2013-11-26

    A solar concentrator including a housing having receiving wall, a reflecting wall and at least two end walls, the receiving, reflecting and end walls defining a three-dimensional volume having an inlet, wherein a vertical axis of the housing is generally perpendicular to the inlet, a receiver mounted on the receiving wall of the housing, the receiver including at least one photovoltaic cell, wherein a vertical axis of the receiver is disposed at a non-zero angle relative to the vertical axis of the housing, at least one clip disposed on the reflecting wall an optical element received within the three-dimensional volume, the optical element including at least one tab, the tab being engaged by the clip to align the optical element with the receiver, and a window received over the inlet to enclose the housing.

  18. Innovative Design of Vertical Axis Wind Turbine

    DEFF Research Database (Denmark)

    Chougule, Prasad

    2013-01-01

    The wind turbines can be classified as: i) Horizontal axis wind turbines (HAWT), and ii) Vertical axis wind turbines (VAWT). The HAWT is fully developed and the size is growing higher. Whereas, the VAWT is not developed because of the less efficiency and vibration issues of big structure. However......, and its aerodynamic characteristics are obtained by an experimental method. A new design is called D2퐴 − 푉퐴푊푇 and a test ring is made to validate the numerical results. A double multiple stream tube method (DMSTM) and blade element method (BEM) are used to determine the numerical performance of a proposed...

  19. Multiscale mathematical modeling of the hypothalamo-pituitary-gonadal axis.

    Science.gov (United States)

    Clément, Frédérique

    2016-07-01

    Although the fields of systems and integrative biology are in full expansion, few teams are involved worldwide into the study of reproductive function from the mathematical modeling viewpoint. This may be due to the fact that the reproductive function is not compulsory for individual organism survival, even if it is for species survival. Alternatively, the complexity of reproductive physiology may be discouraging. Indeed, the hypothalamo-pituitary-gonadal (HPG) axis involves not only several organs and tissues but also intricate time (from the neuronal millisecond timescale to circannual rhythmicity) and space (from molecules to organs) scales. Yet, mathematical modeling, and especially multiscale modeling, can renew our approaches of the molecular, cellular, and physiological processes underlying the control of reproductive functions. In turn, the remarkable dynamic features exhibited by the HPG axis raise intriguing and challenging questions to modelers and applied mathematicians. In this article, we draw a panoramic review of some mathematical models designed in the framework of the female HPG, with a special focus on the gonadal and central control of follicular development. On the gonadal side, the modeling of follicular development calls to the generic formalism of structured cell populations, that allows one to make mechanistic links between the control of cell fate (proliferation, differentiation, or apoptosis) and that of the follicle fate (ovulation or degeneration) or to investigate how the functional interactions between the oocyte and its surrounding cells shape the follicle morphogenesis. On the central, mainly hypothalamic side, models based on dynamical systems with multiple timescales allow one to represent within a single framework both the pulsatile and surge patterns of the neurohormone GnRH. Beyond their interest in basic research investigations, mathematical models can also be at the source of useful tools to study the encoding and decoding of

  20. Research of misalignment between dithered ring laser gyro angle rate input axis and dither axis

    Science.gov (United States)

    Li, Geng; Wu, Wenqi; FAN, Zhenfang; LU, Guangfeng; Hu, Shaomin; Luo, Hui; Long, Xingwu

    2014-12-01

    The strap-down inertial navigation system (SINS), especially the SINS composed by dithered ring laser gyroscope (DRLG) is a kind of equipment, which providing high reliability and performance for moving vehicles. However, the mechanical dither which is used to eliminate the "Lock-In" effect can cause vibration disturbance to the INS and lead to dithering coupling problem in the inertial measurement unit (IMU) gyroscope triad, so its further application is limited. Among DRLG errors between the true gyro rotation rate and the measured rotation rate, the frequently considered one is the input axis misalignment between input reference axis which is perpendicular to the mounting surface and gyro angular rate input axis. But the misalignment angle between DRLG dither axis and gyro angular rate input axis is often ignored by researchers, which is amplified by dither coupling problem and that would lead to negative effects especially in high accuracy SINS. In order to study the problem more clearly, the concept of misalignment between DRLG dither axis and gyro angle rate input axis is researched. Considering the error of misalignment is of the order of 10-3 rad. or even smaller, the best way to measure it is using DRLG itself by means of an angle exciter as an auxiliary. In this paper, the concept of dither axis misalignment is explained explicitly firstly, based on this, the frequency of angle exciter is induced as reference parameter, when DRLG is mounted on the angle exciter in a certain angle, the projections of angle exciter rotation rate and mechanical oscillation rate on the gyro input axis are both sensed by DRLG. If the dither axis has misalignment error with the gyro input axis, there will be four major frequencies detected: the frequency of angle exciter, the dither mechanical frequency, sum and difference frequencies of the former two frequencies. Then the amplitude spectrum of DRLG output signal obtained by the using LabVIEW program. if there are only angle

  1. Triple-axis spectrometer DruechaL

    International Nuclear Information System (INIS)

    Buehrer, W.; Keller, P.

    1996-01-01

    DruechaL is a triple-axis spectrometer located at a cold guide. The characteristics of guide and instrument allow the use of a broad spectral range of neutrons. The resolution in momentum and energy transfer can be tuned to match the experimental requirements by using either collimators or focusing systems (monochromator, antitrumpet, analyser). (author) figs., tabs., refs

  2. Triple-axis spectrometer DruechaL

    Energy Technology Data Exchange (ETDEWEB)

    Buehrer, W.; Keller, P. [Lab. for Neutron Scattering ETH Zurich, Zurich (Switzerland) and Paul Scherrer Institute, Villigen (Switzerland)

    1996-11-01

    DruechaL is a triple-axis spectrometer located at a cold guide. The characteristics of guide and instrument allow the use of a broad spectral range of neutrons. The resolution in momentum and energy transfer can be tuned to match the experimental requirements by using either collimators or focusing systems (monochromator, antitrumpet, analyser). (author) figs., tabs., refs.

  3. Microbes and the gut-brain axis.

    Science.gov (United States)

    Bercik, P; Collins, S M; Verdu, E F

    2012-05-01

    The 'gut-brain' or 'brain-gut axis', depending on whether we emphasize bottom-up or top-bottom pathways, is a bi-directional communication system, comprised of neural pathways, such as the enteric nervous system (ENS), vagus, sympathetic and spinal nerves, and humoral pathways, which include cytokines, hormones, and neuropeptides as signaling molecules. Recent evidence, mainly arising from animal models, supports a role of microbes as signaling components in the gut-brain axis. The purpose of this review is to summarize our current knowledge regarding the role of microbes, including commensals, probiotics and gastrointestinal pathogens, in bottom-up pathways of communication in the gut-brain axis. Although this has clear implications for psychiatric co-morbidity in functional and inflammatory conditions of the gut, the focus of this review will be to discuss the current evidence for a role of bacteria (commensals, probiotics, and pathogens) as key modulators of gut-brain communication. The strongest evidence for a role of microbes as signaling components in the gut-brain axis currently arises from animal studies and indicate that mechanisms of communication are likely to be multiple. There is need for the concepts generated in animal models to be translated to the human in the future. © 2012 Blackwell Publishing Ltd.

  4. The Trading Axis in Irkutsk Downtown

    Directory of Open Access Journals (Sweden)

    Elena Grigoryeva

    2016-10-01

    Full Text Available The article reveals a linear concentration of the trading function in the historical center of Irkutsk. It features historical prerequisites and continuation of the tradition in the post-Soviet period, given the conversion of plants and factories. The article analyses the current state and prospects of modernization of the trading axis with its transformation into a modern public space.

  5. Mechanical axis-derived femoral component rotation in extramedullary total knee arthroplasty: a comparison between femoral transverse axis and transepicondylar axis.

    Science.gov (United States)

    Seo, Jai-Gon; Moon, Young-Wan; Lim, Ji-Soon; Park, Se-Jun; Kim, Sang-Min

    2012-03-01

    Correct rotational alignment of the femoral component is paramount to the success of total knee arthroplasty, but debate continues as to which method is the most reliable. The purpose of this study was to evaluate mechanical axis-derived rotational axis of the femoral component using an extramedullary femoral alignment guide system. Between 2009 and 2010, 60 patients (120 knees) underwent simultaneous bilateral total knee arthroplasty. Postoperative CT scans were performed on all 120 knees. The mechanical axis-derived rotational axis of the femoral component was compared with the surgical transepicondylar axis on CT scans. The femoral component was externally rotated compared with the surgical transepicondylar axis (mean = 1.6°, SD = 2.2°, range: from 4.8° of internal rotation to 7.9° of external rotation). One hundred and nine of the 120 knees (90.8%) were rotated by less than 5° from the surgical transepicondylar axis. All inter-observer observations on CT scans were within a range of ±2.1° and showed no significant differences. Mechanical axis-derived rotational axis of the femoral component was found to be closely related to the surgical transepicondylar axis, to an extent which suggests that the mechanical axis-derived rotational axis could be a new alternative option in determining optimal rotational alignment of the femoral component during total knee arthroplasty. II.

  6. UARS PEM Level 2 AXIS 2 V001 (UARPE2AXIS2) at GES DISC

    Data.gov (United States)

    National Aeronautics and Space Administration — The UARS Particle Environment Monitor (PEM) level 2 Atmosphere X-Ray Imaging Spectrometer (AXIS) unit 2 daily product contains the X-ray high-resolution spectral...

  7. UARS PEM Level 2 AXIS 1 V001 (UARPE2AXIS1) at GES DISC

    Data.gov (United States)

    National Aeronautics and Space Administration — The UARS Particle Environment Monitor (PEM) level 2 Atmosphere X-Ray Imaging Spectrometer (AXIS) unit 1 daily product contains the X-ray high-resolution spectral...

  8. Evaluation of the angles of magnetic axis relative to rotation axis of pulsars

    International Nuclear Information System (INIS)

    Kuz'min, A.D.; Dagkesamanskaya, I.M.

    1983-01-01

    The difference of an observed width of integrated pulse's profile and a beamwidth of pulsar emission is pointed out. A method to evaluate angle #betta# of the magnetic axis relative to the rotation axis is proposed. Values of #betta# are obtained for 308 pulsars. The secular decrease of #betta# has been found. The radius of the emitting region, #betta#-factors and the density of radiating particles are also evaluated

  9. A Portable Single Axis Magnetic Gradiometer

    DEFF Research Database (Denmark)

    Merayo, José M.G.; Petersen, Jan Raagaard; Nielsen, Otto V

    2001-01-01

    The single axis magnetic gradiometer based on two compact detector compensation (CDC) fluxgate ringcore sensors separated 20 cm is described. Despite its high stability and precision better than 1 nT, the calibration procedures are not straightforward. Firstly, the mono-axial measurement does not...... measurements is achieved by using a magnetic dipole of strength 2 mAm(2). In a coil facility, the gradient can be determined with an accuracy of 0.3 nT/m(RMS)....

  10. AXIS - Advanced X-ray Imaging Sarellite

    Science.gov (United States)

    Loewenstein, Michael; AXIS Team

    2018-01-01

    We present an overview of the Advanced X-ray Imaging Satellite (AXIS), a probe mission concept under study to the 2020 Decadal survey. AXIS follows in the footsteps of the spectacularly successful Chandra X-ray Observatory with similar or higher angular resolution and an order of magnitude more collecting area in the 0.3-10 keV band over a 15' field of view. These capabilities are designed to attain a wide range of science goals such as (i) measuring the event horizon scale structure in AGN accretion disks and the spin of supermassive black holes through monitoring of gravitationally microlensed quasars; (ii) understanding AGN and starburst feedback in galaxies and galaxy clusters through direct imaging of winds and interaction of jets and via spatially resolved imaging of galaxies at high-z; (iii) probing the fueling of AGN by resolving the SMBH sphere of influence in nearby galaxies; (iv) investigating hierarchical structure formation and the SMBH merger rate through measurement of the occurrence rate of dual AGN and occupation fraction of SMBHs; (v) advancing SNR physics and galaxy ecology through large detailed samples of SNR in nearby galaxies; (vi) measuring the Cosmic Web through its connection to cluster outskirts. With a nominal 2028 launch, AXIS benefits from natural synergies with LSST, ELTs, ALMA, WFIRST and ATHENA, and will be a valuable precursor to Lynx. AXIS utilizes breakthroughs in the construction of light-weight X-ray optics from mono-crystalline silicon blocks, and developments in the fabrication of large format, small pixel, high readout detectors.

  11. Computational analysis of vertical axis wind turbine arrays

    Science.gov (United States)

    Bremseth, J.; Duraisamy, K.

    2016-10-01

    Canonical problems involving single, pairs, and arrays of vertical axis wind turbines (VAWTs) are investigated numerically with the objective of understanding the underlying flow structures and their implications on energy production. Experimental studies by Dabiri (J Renew Sustain Energy 3, 2011) suggest that VAWTs demand less stringent spacing requirements than their horizontal axis counterparts and additional benefits may be obtained by optimizing the placement and rotational direction of VAWTs. The flowfield of pairs of co-/counter-rotating VAWTs shows some similarities with pairs of cylinders in terms of wake structure and vortex shedding. When multiple VAWTs are placed in a column, the extent of the wake is seen to spread further downstream, irrespective of the direction of rotation of individual turbines. However, the aerodynamic interference between turbines gives rise to regions of excess momentum between the turbines which lead to significant power augmentations. Studies of VAWTs arranged in multiple columns show that the downstream columns can actually be more efficient than the leading column, a proposition that could lead to radical improvements in wind farm productivity.

  12. Analytic representation of electron central-axis depth dose data

    International Nuclear Information System (INIS)

    Jette, D.; Lanzl, L.H.; Rozenfeld, M.; Pagnamenta, A.

    1981-01-01

    We have examined a number of analytic representations of electron central-axis depth dose data current in the literature, testing them against sets of standard depth dose data. One of them, a two-parameter model of Shabason and Hendee, is recommended in situations in which good accuracy (approx.2%) is desired, with the values of the parameters determined by an approximation formula which we have developed elsewhere. For higher accuracy, we have developed a polynomial model which gives, typically, a standard deviation of the fitting polynomial from the data points of 1%, and a maximum deviation of 2%. Fitting polynomials obtained with this method possess the property of having zero slope at the position of actual maximum dose, and generally a fifth-order polynomial (requiring four nonzero coefficients) provided the most acceptable fit. The four parameters involved are determined through inversion of a 4 x 4 matrix, and we have tabulated these four coefficients for the standard data sets. The polynomial model is designed for interpolation in the range between the 100% dose depth and the 10% dose depth, and another fitting curve of the same type can be adjoined to cover depths less than the 100% dose depth. Key words: electron teletherapy, central-axis depth dose, polynomial model, interpolation

  13. Brain-Gut-Microbiota Axis and Mental Health.

    Science.gov (United States)

    Dinan, Timothy G; Cryan, John F

    2017-10-01

    The brain-gut-microbiota axis has been put forward as a new paradigm in neuroscience, which may be of relevance to mental illness. The mechanisms of signal transmission in the brain-gut-microbiota axis are complex and involve bidirectional communications that enable gut microbes to communicate with the brain and the brain to communicate with the microbes. This review assesses the potential usefulness and limitations of the paradigm. A selective literature review was conducted to evaluate the current knowledge in clinical and preclinical brain-gut-microbiota interactions as related to psychiatric disorders. Most published studies in the field are preclinical, and there is so far a lack of clinical studies. Preliminary studies in psychiatric populations support the view of a dysbiosis in some conditions, but studies are often small scale and marred by potential confounding variables. Preclinical studies support the view that psychobiotics ("bacteria which when ingested in adequate amounts have a positive mental health benefit") might be of use in treating some patients with mental health difficulties. To date, we have no well-conducted studies in clinical populations, although there are some studies in healthy volunteers. A cocktail of probiotics has been shown to alter brain activity as monitored by functional magnetic resonance imaging, and Bifidobacterium longum was reported to alter brain electrical activity. It has yet to be convincingly demonstrated that the exciting findings of psychobiotic efficacy demonstrated in preclinical models of psychiatric illness will translate to patients.

  14. Theoretical tool movement required to diamond turn an off-axis paraboloid on axis

    International Nuclear Information System (INIS)

    Thompson, D.C.

    1975-01-01

    High-quality, off-axis parabolic reflectors, required by the CTR and laser-fusion programs at Lawrence Livermore Laboratory (LLL) and other ERDA laboratories, are currently manufactured by hand. There are several drawbacks to this method, including lead times of up to a year, costs in excess of dollars 75,000 for a small reflector, and unsatisfactory limits to the tolerances obtainable. This situation has led to a search for cheaper and more accurate methods of manufacturing off-axis paraboloids. An alternative method, turning the workpiece about its axis on a diamond-turning machine, is presented, and the equations describing the necessary tool movement are derived. A discussion of a particular case suggests that the proposed technique is feasible

  15. The Triple Axis and SPINS Spectrometers.

    Science.gov (United States)

    Trevino, S F

    1993-01-01

    In this paper are described the triple axis and spin polarized inelastic neutron scattering (SPINS) spectrometers which are installed at the NIST Cold Neutron Research Facility (CNRF). The general principle of operation of these two instruments is described in sufficient detail to allow the reader to make an informed decision as to their usefulness for his needs. However, it is the intention of the staff at the CNRF to provide the expert resources for their efficient use in any given situation. Thus, this work is not intended as a user manual but rather as a guide into the range of applicability of the two instruments.

  16. The triple axis and SPINS spectrometers

    International Nuclear Information System (INIS)

    Trevino, S.F.

    1993-01-01

    In this paper are described the triple axis and spin polarized inelastic neutron scattering (SPINS) spectrometers which are installed at the NIST Cold Neutron Research Facility (CNRF). The general principle of operation of these two instruments is described in sufficient detail to allow the reader to make an informed decision as to their usefulness for his needs. However, it is the intention of the staff at the CNRF to provide the expert resources for their efficient use in any given situation. Thus, this work is not intended as a user manual but rather as a guide into the range of applicability of the two instruments

  17. Maintenance of Gastrointestinal Glucose Homeostasis by the Gut-Brain Axis.

    Science.gov (United States)

    Chen, Xiyue; Eslamfam, Shabnam; Fang, Luoyun; Qiao, Shiyan; Ma, Xi

    2017-01-01

    Gastrointestinal homeostasis is a dynamic balance under the interaction between the host, GI tract, nutrition and energy metabolism. Glucose is the main energy source in living cells. Thus, glucose metabolic disorders can impair normal cellular function and endanger organisms' health. Diseases that are associated with glucose metabolic disorders such as obesity, diabetes, hypertension, and other metabolic syndromes are in fact life threatening. Digestive system is responsible for food digestion and nutrient absorption. It is also involved in neuronal, immune, and endocrine pathways. In addition, the gut microbiota plays an essential role in initiating signal transduction, and communication between the enteric and central nervous system. Gut-brain axis is composed of enteric neural system, central neural system, and all the efferent and afferent neurons that are involved in signal transduction between the brain and gut-brain. Gut-brain axis is influenced by the gut-microbiota as well as numerous neurotransmitters. Properly regulated gut-brain axis ensures normal digestion, absorption, energy production, and subsequently maintenance of glucose homeostasis. Understanding the underlying regulatory mechanisms of gut-brain axis involved in gluose homeostasis would enable us develop more efficient means of prevention and management of metabolic disease such as diabetic, obesity, and hypertension. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  18. Modulation of the Hypothalamic-Pituitary-Adrenal Axis by Early Life Stress Exposure

    Science.gov (United States)

    van Bodegom, Miranda; Homberg, Judith R.; Henckens, Marloes J. A. G.

    2017-01-01

    Exposure to stress during critical periods in development can have severe long-term consequences, increasing overall risk on psychopathology. One of the key stress response systems mediating these long-term effects of stress is the hypothalamic-pituitary-adrenal (HPA) axis; a cascade of central and peripheral events resulting in the release of corticosteroids from the adrenal glands. Activation of the HPA-axis affects brain functioning to ensure a proper behavioral response to the stressor, but stress-induced (mal)adaptation of the HPA-axis' functional maturation may provide a mechanistic basis for the altered stress susceptibility later in life. Development of the HPA-axis and the brain regions involved in its regulation starts prenatally and continues after birth, and is protected by several mechanisms preventing corticosteroid over-exposure to the maturing brain. Nevertheless, early life stress (ELS) exposure has been reported to have numerous consequences on HPA-axis function in adulthood, affecting both its basal and stress-induced activity. According to the match/mismatch theory, encountering ELS prepares an organism for similar (“matching”) adversities during adulthood, while a mismatching environment results in an increased susceptibility to psychopathology, indicating that ELS can exert either beneficial or disadvantageous effects depending on the environmental context. Here, we review studies investigating the mechanistic underpinnings of the ELS-induced alterations in the structural and functional development of the HPA-axis and its key external regulators (amygdala, hippocampus, and prefrontal cortex). The effects of ELS appear highly dependent on the developmental time window affected, the sex of the offspring, and the developmental stage at which effects are assessed. Albeit by distinct mechanisms, ELS induced by prenatal stressors, maternal separation, or the limited nesting model inducing fragmented maternal care, typically results in HPA-axis

  19. Modulation of Gut Microbiota-Brain Axis by Probiotics, Prebiotics, and Diet.

    Science.gov (United States)

    Liu, Xiaofei; Cao, Shangqing; Zhang, Xuewu

    2015-09-16

    There exists a bidirectional communication system between the gastrointestinal tract and the brain. Increasing evidence shows that gut microbiota can play a critical role in this communication; thus, the concept of a gut microbiota and brain axis is emerging. Here, we review recent findings in the relationship between intestinal microbes and brain function, such as anxiety, depression, stress, autism, learning, and memory. We highlight the advances in modulating brain development and behavior by probiotics, prebiotics, and diet through the gut microbiota-brain axis. A variety of mechanisms including immune, neural, and metabolic pathways may be involved in modulation of the gut microbiota-brain axis. We also discuss some future challenges. A deeper understanding of the relationship between the gut bacteria and their hosts is implicated in developing microbial-based therapeutic strategies for brain disorders.

  20. Role of the Hypothalamic-Pituitary-Adrenal Axis in Developmental Programming of Health and Disease

    Science.gov (United States)

    Xiong, Fuxia; Zhang, Lubo

    2012-01-01

    Adverse environments during the fetal and neonatal development period may permanently program physiology and metabolism, and lead to increased risk of diseases in later life. Programming of the hypothalamic-pituitary-adrenal (HPA) axis is one of the key mechanisms that contribute to altered metabolism and response to stress. Programming of the HPA axis often involves epigenetic modification of the glucocorticoid receptor (GR) gene promoter, which influences tissue-specific GR expression patterns and response to stimuli. This review summarizes the current state of research on the HPA axis and programming of health and disease in the adult, focusing on the epigenetic regulation of GR gene expression patterns in response to fetal and neonatal stress. Aberrant GR gene expression patterns in the developing brain may have a significant negative impact on protection of the immature brain against hypoxic-ischemic encephalopathy in the critical period of development during and immediately after birth. PMID:23200813

  1. Ambiguous involvement

    DEFF Research Database (Denmark)

    Dannesboe, Karen Ida

    2016-01-01

    This edited collection shows that good parenthood is neither fixed nor stable. The contributors show how parenthood is equally done by men, women and children, in and through practices involving different normative guidelines. The book explores how normative layers of parenthood are constituted...... by notions such as good childhood, family ideals, national public health and educational strategies. The authors illustrate how different versions of parenthood coexist and how complex sets of actions are demanded to fulfil today’s expectations of parenthood in Western societies. This interdisciplinary book...

  2. Methamphetamine and the hypothalamic-pituitary-adrenal axis

    Directory of Open Access Journals (Sweden)

    Damian Gabriel Zuloaga

    2015-05-01

    Full Text Available Psychostimulants such as methamphetamine (MA induce significant alterations in the function of the hypothalamic-pituitary-adrenal (HPA axis. These changes in HPA axis function are associated with altered stress-related behaviors and might contribute to addictive processes such as relapse. In this mini-review we discuss acute and chronic effects of MA (adult and developmental exposure on the HPA axis, including effects on HPA axis associated genes/proteins, brain regions, and behaviors such as anxiety and depression. A better understanding of the mechanisms through which MA affects the HPA axis may lead to more effective treatment strategies for MA addiction.

  3. VERITAS: Versatile Triple-Axis Spectrometer

    Energy Technology Data Exchange (ETDEWEB)

    Park, Sung Il

    2006-04-15

    Korea Atomic Energy Research Institute is planning to build a cold neutron triple-axis spectrometer at HANARO, the 30 MW research reactor. The spectrometer is expected to be completed in 2008 with the following configuration from the upstream to the downstream. Guide Supermirror m = 2, In-pile Straight Section, {approx} 5 m Curved Guide, {approx} 26 m w/ R 1500 m Straight Guide before the Instrument, {approx} 40 m Filters PG and Be Neutron Velocity Selector (Future) Monochromators Vertically Focusing Monochromators PG(002) and Heusler(111) Doubly Focusing Monochromators (Future) Monochromator-Sample Distance 2 m Collimation C1 Soller Collimators, 20', 40' 80'Beam Height at the Sample Table 1.5 m Sample-Analyzer Distance 1.0 m Collimation C2 Soller Collimators, 20', 40', 80' Radial Collimator Analyzers Horizontally Focusing Analyzers w/ Fixed Vertical Focusing PG(002) and Heusler(111) Analyzer-Detector Distance 0.5 m Detectors 5 cm Tube Detector 25 cm wide Position Sensitive Detector Once completed, the neutron flux at sample is expected to surpass that of SPINS at NCNR, making this instrument one of the most powerful 2nd generation cold neutron triple-axis spectrometers in the world.

  4. VERITAS: Versatile Triple-Axis Spectrometer

    International Nuclear Information System (INIS)

    Park, Sung Il

    2006-04-01

    Korea Atomic Energy Research Institute is planning to build a cold neutron triple-axis spectrometer at HANARO, the 30 MW research reactor. The spectrometer is expected to be completed in 2008 with the following configuration from the upstream to the downstream. Guide Supermirror m = 2, In-pile Straight Section, ∼ 5 m Curved Guide, ∼ 26 m w/ R 1500 m Straight Guide before the Instrument, ∼ 40 m Filters PG and Be Neutron Velocity Selector (Future) Monochromators Vertically Focusing Monochromators PG(002) and Heusler(111) Doubly Focusing Monochromators (Future) Monochromator-Sample Distance 2 m Collimation C1 Soller Collimators, 20', 40' 80'Beam Height at the Sample Table 1.5 m Sample-Analyzer Distance 1.0 m Collimation C2 Soller Collimators, 20', 40', 80' Radial Collimator Analyzers Horizontally Focusing Analyzers w/ Fixed Vertical Focusing PG(002) and Heusler(111) Analyzer-Detector Distance 0.5 m Detectors 5 cm Tube Detector 25 cm wide Position Sensitive Detector Once completed, the neutron flux at sample is expected to surpass that of SPINS at NCNR, making this instrument one of the most powerful 2nd generation cold neutron triple-axis spectrometers in the world

  5. ATX-LPA axis induces expression of OPN in hepatic cancer cell SMMC7721.

    Science.gov (United States)

    Zhang, Rihua; Zhang, Zhihong; Pan, Xiaolin; Huang, Xiayue; Huang, Zuhu; Zhang, Guoxin

    2011-03-01

    Osteopontin (OPN) and autotaxin (ATX) are important chemokines involved in the survival, proliferation, migration, invasion, and metastasis of many cancer cells. The focus of the study was to investigate the relationship between OPN and ATX-lysophosphatidic acid (LPA) axis. The expression of OPN and its cellular cascades were determined by western blot and real-time quantitative transcription polymerase chain reaction (real-time PCR) analyses. Cell migration activity was determined by a Transwell-migration assay. In comparison with nontreated cells, we found that the ATX-LPA axis upregulated OPN expression by 2.91-fold in protein levels and 2.52-fold in mRNA levels. The ATX-LPA axis activates Akt and ATX/LPC-induced OPN expression in SMMC7721 cells was largely reduced by the inhibitors of phosphatidylinositol 3-kinase (PI3K)/Akt or LPA receptor. This study provides the first evidence that the induction of the OPN expression by ATX-LPA axis was mediated by the activation of Akt through LPA receptors and OPN was required for migration of SMMC7721 cells induced by ATX-LPA axis. Copyright © 2010 Wiley-Liss, Inc.

  6. Stimuli-Driven Control of the Helical Axis of Self-Organized Soft Helical Superstructures.

    Science.gov (United States)

    Bisoyi, Hari Krishna; Bunning, Timothy J; Li, Quan

    2018-03-30

    Supramolecular and macromolecular functional helical superstructures are ubiquitous in nature and display an impressive catalog of intriguing and elegant properties and performances. In materials science, self-organized soft helical superstructures, i.e., cholesteric liquid crystals (CLCs), serve as model systems toward the understanding of morphology- and orientation-dependent properties of supramolecular dynamic helical architectures and their potential for technological applications. Moreover, most of the fascinating device applications of CLCs are primarily determined by different orientations of the helical axis. Here, the control of the helical axis orientation of CLCs and its dynamic switching in two and three dimensions using different external stimuli are summarized. Electric-field-, magnetic-field-, and light-irradiation-driven orientation control and reorientation of the helical axis of CLCs are described and highlighted. Different techniques and strategies developed to achieve a uniform lying helix structure are explored. Helical axis control in recently developed heliconical cholesteric systems is examined. The control of the helical axis orientation in spherical geometries such as microdroplets and microshells fabricated from these enticing photonic fluids is also explored. Future challenges and opportunities in this exciting area involving anisotropic chiral liquids are then discussed. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Emotions and Steroid Secretion in Aging Men: A Multi—Study Report

    Directory of Open Access Journals (Sweden)

    Andreas Walther

    2017-09-01

    association between age and symptoms of anxiety or depression in VE and FA men, respectively. Both hair cortisol and progesterone seem to influence age-related alterations in anger experience. Age-related alterations in the hypothalamic-pituitary-adrenal (HPA axis and the hypothalamic-pituitary-gonadal (HPG axis emerge as promising avenues to further investigate the decrease in experienced negative emotions in aging men.

  8. [Congenital hypogonadotropic hypogonadism and Kallmann syndrome in males].

    Science.gov (United States)

    Ghervan, Cristina; Young, Jacques

    2014-02-01

    Congenital hypogonadotropic hypogonadism (CHH) and Kallmann syndrome (KS) are a group of rare disorders responsible for complete or partial pubertal failure due to lack or insufficient secretion of the pituitary gonadotropins LH and FSH. The underlying neuroendocrine abnormalities are classically divided into two main groups: molecular defects of the gonadotrope cascade leading to isolated normosmic CHH (nCHH), and developmental abnormalities affecting the hypothalamic location of GnRH neurons, but also olfactory bulbs and tracts morphogenesis and responsible for KS. Identification of genetic abnormalities related to CHH/KS has provided major insights into the pathways critical for the development, maturation and function of the gonadotrope axis. In patients affected by nCHH, particularly in familial cases, genetic alterations affecting GnRH secretion (mutations in GNRH1, GPR54/KISS1R and TAC3 and TACR3) or the GnRH sensitivity of gonadotropic cells (GNRHR) have been found. Mutations in KAL1, FGFR1/FGF8/FGF17, PROK2/PROKR2, NELF, CHD7, HS6ST1, WDR11, SEMA3A, SOX10, IL17RD2, DUSP6, SPRY4, and FLRT3 have been associated with KS but sometimes also with its milder hyposmic/normosmic CHH clinical variant. A number of observations, particularly in sporadic cases, suggest that CHH/KS is not always a monogenic mendelian disease as previously thought but rather a digenic or potentially oligogenic condition. Before the age of 18 years, the main differential diagnosis of isolated nCHH is the relatively frequent constitutional delay of growth and puberty (CDGP). However, in male patients with pubertal delay and low gonadotropin levels, the presence of micropenis and/or cryptorchidism argues strongly in favor of CHH and against CDGP. CHH/KS are not always congenital life-long disorders as initially thought, because in nearly 10 % of patients the disease seems not permanent, as evidenced by partial recovery of the pulsatile activity of the hypothalamic-pituitary-gonadal axis

  9. Photoperiod modulation of aggressive behavior is independent of androgens in a tropical cichlid fish.

    Science.gov (United States)

    Gonçalves-de-Freitas, Eliane; Carvalho, Thaís Billalba; Oliveira, Rui F

    2014-10-01

    Photoperiod is a major environmental cue that signals breeding conditions in animals living in temperate climates. Therefore, the activity of the reproductive (i.e. hypothalamic-pituitary-gonadal, HPG) axis and of the expression of reproductive behaviors, including territoriality, is responsive to changes in day length. However, at low latitudes the seasonal variation in day length decreases dramatically and photoperiod becomes less reliable as a breeding entraining cue in tropical species. In spite of this, some tropical mammals and birds have been found to still respond to small amplitude changes in photoperiod (e.g. 17min). Here we tested the effect of 2 photoperiod regimes, referred to as long-day (LD: 16L:08D) and short-day (SD: 08L:16D), on the activity of the HPG axis, on aggressive behavior and in the androgen response to social challenges in males of the tropical cichlid fish Tilapia rendalli. For each treatment, fish were transferred from a pre-treatment photoperiod of 12L:12D to their treatment photoperiod (either LD or SD) in which they were kept for 20days on stock tanks. Afterwards, males were isolated for 4days in glass aquaria in order to establish territories and initial androgen levels (testosterone, T; 11-ketotestosterone, KT) were assessed. On the 4th day, territorial intrusions were promoted such that 1/3 of the isolated males acted as residents and another 1/3 as intruders. Territorial intrusions lasted for 1h to test the effects of a social challenge under different photoperiod regimes. Photoperiod treatment (either SD or LD) failed to induce significant changes in the HPG activity, as measured by androgen levels and gonadosomatic index. However, SD increased the intensity of aggressive behaviors and shortened the time to settle a dominance hierarchy in an androgen-independent manner. The androgen responsiveness to the simulated territorial intrusion was only present in KT but not for T. The percent change in KT levels in response to the

  10. Metabolic and cardiovascular outcomes of fatherhood: results from a cohort of study in subjects with sexual dysfunction.

    Science.gov (United States)

    Fisher, Alessandra D; Rastrelli, Giulia; Bandini, Elisa; Corona, Giovanni; Balzi, Daniela; Melani, Cecilia; Monami, Matteo; Matta, Vanessa; Mannucci, Edoardo; Maggi, Mario

    2012-11-01

    Previous cross-sectional and longitudinal studies reported a negative correlation between fatherhood and testosterone (T) levels, likely due to a centrally mediated downregulation of the hypothalamic-pituitary-gonadal axis. Moreover, epidemiological data indicate that fatherhood might affect metabolic and cardiovascular outcomes, although different results have been reported. Up to now, no studies have evaluated these associations in a population of men seeking treatment for sexual dysfunction (SD). To explore biological and clinical correlates of number of children (NoC) and its possible associations with forthcoming major cardiovascular events (MACE) in a sample of men with SD. A consecutive series of 4,045 subjects (mean age 52 ± 13.1 years old) attending the Outpatient Clinic for SD was retrospectively studied. A subset of the previous sample (N = 1,687) was enrolled in a longitudinal study. Information on MACE was obtained through the City of Florence Registry Office. Among patients studied, 31.6% had no children, while 26.3% reported having one child, 33.4% two, and 8.8% three or more children. Although fatherhood was negatively related with follicle-stimulating hormone levels and positively with testis volume, we found a NoC-dependent, stepwise decrease in T plasma levels, not compensated by a concomitant increase in luteinizing hormone. NoC was associated with a worse metabolic and cardiovascular profile, as well as worse penile blood flows and a higher prevalence of metabolic syndrome (MetS). In the longitudinal study, after adjusting for confounders, NoC was independently associated with a higher incidence of MACE. However, when the presence of MetS was introduced as a further covariate, the association was no longer significant. This study supports the hypothesis that bond maintenance contexts and fatherhood are associated with an adaptive downregulation of the gonadotropin-gonadal axis, even in a sample of men with SD. Moreover, our data suggest that

  11. Cognitive, emotional and psychosocial functioning of girls treated with pharmacological puberty blockage for idiopathic central precocious puberty

    Directory of Open Access Journals (Sweden)

    Slawomir Wojniusz

    2016-07-01

    Full Text Available Central precocious puberty (CPP develops due to premature activation of the hypothalamic-pituitary-gonadal (HPG axis, resulting in early pubertal changes and rapid bone maturation. CPP is associated with lower adult height and increased risk for development of psychological problems. Standard treatment of CPP is based on postponement of pubertal development by blockade of the HPG axis with gonadotropin releasing hormone analogs (GnRHa leading to abolition of gonadal sex hormones synthesis. Whereas the hormonal and auxological effects of GnRHa are well researched, there is a lack of knowledge whether GnRHa treatment influences psychological functioning of treated children, despite the fact that prevention of psychological problems is used as one of the main reasons for treatment initiation. In the present study we seek to address this issue by exploring differences in cognitive function, behavior, emotional reactivity, and psychosocial problems between GnRHa treated CPP girls and age-matched controls.Fifteen girls with idiopathic CPP; median age 10.4 years, treated with slow-release GnRHa (triptorelin acetate – Decapeptyl SR ® 11.25 and 15 age-matched controls, were assessed with a comprehensive test battery consisting of paper and pencil tests, computerized tasks, behavioral paradigms, heart rate variability, and questionnaires filled in by the children’s parents. Both groups showed very similar scores with regard to cognitive performance, behavioral and psychosocial problems. Compared to controls, treated girls displayed significantly higher emotional reactivity (p = 0.016; Cohen’s d = 1.04 on one of the two emotional reactivity task conditions. Unexpectedly, the CPP group showed significantly lower resting heart rates than the controls (p = 0.004; Cohen’s d = 1.03; lower heart rate was associated with longer treatment duration (r = - 0.582, p = 0.037. The results suggest that GnRHa treated CPP girls do not differ in their cognitive or

  12. RITA-type triple axis spectrometers

    International Nuclear Information System (INIS)

    Roennow, H.M.

    2001-01-01

    The RITA spectrometer at Risoe National Laboratory was the first to incorporate a complete re-thinking of the neutron-path from source, through detector to analysis. Since then, other RITA-type spectrometers such as SPINS at NIST, RITA-II at PSI have been built, and several new spectrometers around the world are adapting the same philosophy. The main novelty of RITA was the introduction of a single back-end tank featuring both an analyser block with multiple individually turnable analyser blades and a 2D position sensitive detector. Several new triple-axis spectrometers are presently being built at existing and future sources, and almost all of them have learnt from the experience with RITA. (R.P.)

  13. Polarized triple-axis spectrometer TASP

    Energy Technology Data Exchange (ETDEWEB)

    Boeni, P.; Keller, P. [Lab. for Neutron Scattering ETH Zurich, Zurich (Switzerland) and Paul Scherrer Institute, Villigen (Switzerland)

    1996-11-01

    The polarized triple-axis spectrometer TASP at SINQ has been optimized for measuring magnetic cross sections in condensed matter. The neutrons are polarized or analyzed either by means of benders or Heusler monochromators. The beam divergence, i.e. the intensity, and the spectral range of the neutrons is rather large because of the supermirror coatings of the feeding neutron guide. The intensity can be further increased at the sample position by means of a focussing monochromator and a focussing anti-trumpet. The end position of TASP allows the tailoring of the neutron beam already before the monochromator and to scatter neutrons over very wide ranges of angles. (author) 6 figs., 1 tab., 8 refs.

  14. Polarized triple-axis spectrometer TASP

    International Nuclear Information System (INIS)

    Boeni, P.; Keller, P.

    1996-01-01

    The polarized triple-axis spectrometer TASP at SINQ has been optimized for measuring magnetic cross sections in condensed matter. The neutrons are polarized or analyzed either by means of benders or Heusler monochromators. The beam divergence, i.e. the intensity, and the spectral range of the neutrons is rather large because of the supermirror coatings of the feeding neutron guide. The intensity can be further increased at the sample position by means of a focussing monochromator and a focussing anti-trumpet. The end position of TASP allows the tailoring of the neutron beam already before the monochromator and to scatter neutrons over very wide ranges of angles. (author) 6 figs., 1 tab., 8 refs

  15. Arterial thoracic vascularization in some deer species: pampas deer (Ozotoceros bezoarticus), brown brocket deer (Mazama gouazoubira) and axis deer (Axis axis).

    Science.gov (United States)

    Pérez, W; Erdoğan, S

    2014-12-01

    In this study, the arterial distributions of the aortic arches of three deer species (Axis axis, Ozotoceros bezoarticus and Mazama gouazoubira) were described. The animals were dissected immediately after being found dead. Latex injection method was used to observe the vascularization of the thorax. The branching pattern of the arteries of the thoracic aorta in O. bezoarticus was similar to domestic ruminants. In the M. gouazoubira and A. axis, there were no bicarotid trunk. Interestingly, the first branch of the brachiocephalic trunk was the left costocervical trunk in A. axis. Then, brachiocephalic trunk was divided into right and left subclavian arteries. M. gouazoubira and A. axis in contrast to O. bezoarticus were different when compared with other ruminants, and the absence of bicarotid trunk was more striking than previous reports. © 2014 Blackwell Verlag GmbH.

  16. Role of thymulin on the somatotropic axis in vivo.

    Science.gov (United States)

    Reggiani, Paula C; Martines, Eliana V; Camihort, Gisela A; Poch, Brenda; Goya, Rodolfo G; Cónsole, Gloria M

    2012-09-04

    There is clear evidence for the existence of a bi-directional thymus-somatotropic axis and several studies suggest that the thymic peptide thymulin may be involved in this communication. We undertook to assess the impact of serum thymulin immunoneutralization in C57BL/6 mice and that of neonatal thymulin gene therapy (NTGT) in nude mice on body weight (BW) gain and on the histomorphometric profile of the somatotrope population. Immunoneutralization of thymulin was done from postnatal day 1 to 35 by i.p. injections of rabbit anti-thymulin serum (α-FTS) and normal rabbit serum (NRS) in controls. NTGT was implemented in nudes using an adenoviral vector expressing a synthetic gene for thymulin (RAd-FTS). On postnatal day 1, heterozygous (nu/+) and homozygous (nu/nu) pups received a single bilateral i.m. injection either RAd-FTS or RAd-GFP (a control vector expressing green fluorescent protein). BW gain was recorded and at the end of the study the pituitaries were immunostained for growth hormone (GH). Serum GH and thymulin were determined by radioimmunoassay and bioassay, respectively. Thymulin immunoneutralization induced a significant decrease in BW gain, serum GH and somatotrope cell density as well as an increase in somatotrope cell size. NTGT markedly increased BW gain, serum thymulin (P<0.01) and somatotrope cell and volume density in nu/nu mice. Our results suggest that thymulin plays a relevant physiological role on the thymus-somatotropic axis in mice. Copyright © 2012 Elsevier Inc. All rights reserved.

  17. A progesterone-brown fat axis is involved in regulating fetal growth.

    NARCIS (Netherlands)

    McIlvride, Saraid; Mushtaq, Aleena; Papacleovoulou, Georgia; Hurling, Chloe; Steel, Jennifer; Jansen, Eugène; Abu-Hayyeh, Shadi; Williamson, Catherine

    2017-01-01

    Pregnancy is associated with profound maternal metabolic changes, necessary for the growth and development of the fetus, mediated by reproductive signals acting on metabolic organs. However, the role of brown adipose tissue (BAT) in regulating gestational metabolism is unknown. We show that BAT

  18. Current concepts in neuroendocrine disruption.

    Science.gov (United States)

    León-Olea, Martha; Martyniuk, Christopher J; Orlando, Edward F; Ottinger, Mary Ann; Rosenfeld, Cheryl; Wolstenholme, Jennifer; Trudeau, Vance L

    2014-07-01

    In the last few years, it has become clear that a wide variety of environmental contaminants have specific effects on neuroendocrine systems in fish, amphibians, birds and mammals. While it is beyond the scope of this review to provide a comprehensive examination of all of these neuroendocrine disruptors, we will focus on select representative examples. Organochlorine pesticides bioaccumulate in neuroendocrine areas of the brain that directly regulate GnRH neurons, thereby altering the expression of genes downstream of GnRH signaling. Organochlorine pesticides can also agonize or antagonize hormone receptors, adversely affecting crosstalk between neurotransmitter systems. The impacts of polychlorinated biphenyls are varied and in many cases subtle. This is particularly true for neuroedocrine and behavioral effects of exposure. These effects impact sexual differentiation of the hypothalamic-pituitary-gonadal axis, and other neuroendocrine systems regulating the thyroid, metabolic, and stress axes and their physiological responses. Weakly estrogenic and anti-androgenic pollutants such as bisphenol A, phthalates, phytochemicals, and the fungicide vinclozolin can lead to severe and widespread neuroendocrine disruptions in discrete brain regions, including the hippocampus, amygdala, and hypothalamus, resulting in behavioral changes in a wide range of species. Behavioral features that have been shown to be affected by one or more these chemicals include cognitive deficits, heightened anxiety or anxiety-like, sociosexual, locomotor, and appetitive behaviors. Neuroactive pharmaceuticals are now widely detected in aquatic environments and water supplies through the release of wastewater treatment plant effluents. The antidepressant fluoxetine is one such pharmaceutical neuroendocrine disruptor. Fluoxetine is a selective serotonin reuptake inhibitor that can affect multiple neuroendocrine pathways and behavioral circuits, including disruptive effects on reproduction and

  19. Opioids Increase Sexual Dysfunction in Patients With Non-Cancer Pain.

    Science.gov (United States)

    Ajo, Raquel; Segura, Ana; Inda, María M; Planelles, Beatriz; Martínez, Luz; Ferrández, Guillermina; Sánchez, Angel; César Margarit; Peiró, Ana-María

    2016-09-01

    Long-term opioid therapy has been found to have a strong impact on the hypothalamic-pituitary-gonadal axis that can be manifested clinically by sexual dysfunction (SD). This event is rarely reported and thus unnoticed and undertreated. To analyze the presence of SD in a large group of patients receiving long-term opioids. A descriptive, cross-sectional pilot study of sexual health was conducted for 2 years in 750 consecutive ambulatory patients with chronic non-cancer pain (CNP) receiving opioids for at least 12 months. Cases that reported SD and matched controls were included. Standardized questionnaires and medical record reviews were used to assess rates of pain at diagnosis, daily morphine equivalent doses, and opioid adverse effects. Sexual function was determined by the Female Sexual Function Index (FSFI; scores = 2-36) and the International Index of Erectile Function erectile function domain (IIEF-EF; scores = 1-30). Thirty-three percent of 33% of 750 patients with CNP recorded SD based on their spontaneous notification at the pain unit. Men reported SD significantly more frequently than women (33% vs 25%, respectively, P < .05), although they reported having a regular partner (84% vs 70%, P = .03) and a sexually active life (69% vs 34%, respectively, P = .00) significantly more often. FSFI scores were significantly influenced by sexual activity in lubrication and arousal. IIEF scores were significantly determined by age in satisfaction with sexual intercourse and overall satisfaction. The morphine equivalent dose was significant higher in men than in women (38%; median = 70 mg/d, interquartile range = 43.1-170, 115.5 ± 110.3 mg/d vs median = 60 mg/d, interquartile range = 30-100.6, 76.67 ± 63.79 mg/d, P = .016) at the same mean intensity of pain (P = .54), which correlated to FSFI scores (r = -0.313, P = .01). SD is prevalent in patients with CNP and higher in men who received a significantly higher mean opioid dose at the same intensity pain

  20. Improved final predicted height with the injection of leuprolide in children with earlier puberty: A retrospective cohort study.

    Directory of Open Access Journals (Sweden)

    Yi-Chun Lin

    Full Text Available The adult height of children with early onset puberty is limited by the premature maturation of hypothalamic-pituitary-gonadal axis. To evaluate the effects of gonadotropin-releasing hormone analog (GnRHa treatment on the final height (FH and bone maturation rate (BMR in girls with early puberty (EP or idiopathic central precocious puberty (ICPP, we examined data from girls who were diagnosed with EP or ICPP and underwent GnRHa (Leuplin Depot: 3.75 mg/month at China Medical University Hospital, in Taiwan, between 2006 and 2015. Patients were observed until the achievement of FH and divided into an "EP group" (T-ep and "ICPP group" (T-icpp according to the age of onset of puberty. Eighty-seven patients were enrolled (T-ep, N = 44, puberty onset at 8-10 years; T-icpp, N = 43, puberty onset before 8 years. The demographic data of girls with EP or IPP was characterized. BMR, change in predicted final height (PFH after GnRHa treatment, target height (TH and FH were measured. After GnRHa treatment, the study groups (T-ep: 160.24±6.18 cm, T-icpp: 158.99±5.92 cm both had higher PFH than at initiation (T-ep: 159.83±7.19 cm, T-icpp: 158.58±5.93 cm. There was deceleration of BMR in both groups (T-ep: 0.57±0.39; T-icpp: 0.97±0.97 and a significant difference between the groups (p = 0.027. The gap in FH standard deviation scores (SDS and TH SDS had a significant difference in T-ep (p = 0.045 but not in T-icpp. Moreover, there was no difference in the gap of PFH SDS between the 1st and final treatment in both groups. We concluded that GnRHa decelerated BMR in girls with earlier puberty. Further prospective clinical studies are warranted.

  1. A small population of hypothalamic neurons govern fertility: the critical role of VAX1 in GnRH neuron development and fertility maintenance.

    Science.gov (United States)

    Hoffmann, Hanne M; Mellon, Pamela L

    2016-01-01

    Fertility depends on the correct maturation and function of approximately 800 gonadotropin-releasing hormone (GnRH) neurons in the brain. GnRH neurons are at the apex of the hypothalamic-pituitary-gonadal axis that regulates fertility. In adulthood, GnRH neurons are scattered throughout the anterior hypothalamic area and project to the median eminence, where GnRH is released into the portal vasculature to stimulate release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from the pituitary. LH and FSH then regulate gonadal steroidogenesis and gametogenesis. Absence of GnRH neurons or inappropriate GnRH release leads to infertility. Despite the critical role of GnRH neurons in fertility, we still have a limited understanding of the genes responsible for proper GnRH neuron development and function in adulthood. GnRH neurons originate in the olfactory placode then migrate into the brain. Homeodomain transcription factors expressed within GnRH neurons or along their migratory path are candidate genes for inherited infertility. Using a combined in vitro and in vivo approach, we have identified Ventral Anterior Homeobox 1 ( Vax1 ) as a novel homeodomain transcription factor responsible for GnRH neuron maturation and fertility. GnRH neuron counts in Vax1 knock-out embryos revealed Vax1 to be required for the presence of GnRH-expressing cells at embryonic day 17.5 (E17.5), but not at E13.5. To localize the effects of Vax1 on fertility, we generated Vax1 flox mice and crossed them with Gnrh cre mice to specifically delete Vax1 within GnRH neurons. GnRH staining in Vax1 flox/flox :GnRH cre mice show a total absence of GnRH expression in the adult. We performed lineage tracing in Vax1 flox/flox :GnRH cre :RosaLacZ mice which proved GnRH neurons to be alive, but incapable of expressing GnRH. The absence of GnRH leads to delayed puberty, hypogonadism and complete infertility in both sexes. Finally, using the immortalized model GnRH neuron cell lines, GN11 and

  2. Reproductive hormone analyses and effects of adjuvant zoledronic acid in early breast cancer – An AZURE (BIG 01/04 sub-study

    Directory of Open Access Journals (Sweden)

    Caroline Wilson

    2017-11-01

    Full Text Available Purpose: Adjuvant bisphosphonates have been shown to improve disease outcomes in early breast cancer in women who are postmenopausal at the start of treatment. We explored the influence of pretreatment serum levels of reproductive hormones in the hypothalamic-pituitary-gonadal (HPG axis from a subset of patients included in the AZURE trial to investigate their impact on disease recurrence and whether reproductive hormone measurements are of value in selecting patients for treatment with adjuvant zoledronic acid.Patients and methods; The AZURE trial is an academic, multi-centre, international phase III trial that randomised patients to standard adjuvant therapy (chemotherapy and/or endocrine therapy±intravenous zoledronic acid, 4 mg for 5 years. Serum from 865 patients taken at randomisation was stored at −80 °C prior to central batch analysis for inhibin A, oestradiol and follicle stimulating hormone (FSH. We assessed the clinical value of pretreatment hormone levels for predicting invasive disease free survival (IDFS, skeletal recurrence and distant recurrence and response to treatment with zoledronic acid. Results: Oestradiol in the postmenopausal range (26 IU/l was associated with a longer time to bone as first recurrence (HR 0.66 95%CI: 0.41–1.04 p=0.072 compared to an FSH ≤26 IU/l. When all 3 hormone levels were within the assay specified postmenopausal range, a trend to improved IDFS was seen with addition of zoledronic acid in biochemically postmenopausal women only (postmenopausal HR=0.81; 95%CI: 0.54–1.22, non-postmenopausal HR=0.99; 95%CI: 0.69–1.39 with risk reductions that mirrored the results of the main AZURE study, although the interaction between menopausal status and treatment effect was not statistically significant (p=0.47. Conclusion: Oestradiol and FSH may influence the pattern of disease recurrence with postmenopausal levels possibly creating a less conducive environment for the

  3. Reproductive hormone analyses and effects of adjuvant zoledronic acid in early breast cancer - An AZURE (BIG 01/04) sub-study.

    Science.gov (United States)

    Wilson, Caroline; Hinsley, Samantha; Marshall, Helen; Cameron, David; Bell, Richard; Dodwell, David; Coleman, Robert E

    2017-11-01

    Adjuvant bisphosphonates have been shown to improve disease outcomes in early breast cancer in women who are postmenopausal at the start of treatment. We explored the influence of pretreatment serum levels of reproductive hormones in the hypothalamic-pituitary-gonadal (HPG) axis from a subset of patients included in the AZURE trial to investigate their impact on disease recurrence and whether reproductive hormone measurements are of value in selecting patients for treatment with adjuvant zoledronic acid.Patients and methods; The AZURE trial is an academic, multi-centre, international phase III trial that randomised patients to standard adjuvant therapy (chemotherapy and/or endocrine therapy)±intravenous zoledronic acid, 4 mg for 5 years. Serum from 865 patients taken at randomisation was stored at -80 °C prior to central batch analysis for inhibin A, oestradiol and follicle stimulating hormone (FSH). We assessed the clinical value of pretreatment hormone levels for predicting invasive disease free survival (IDFS), skeletal recurrence and distant recurrence and response to treatment with zoledronic acid. Oestradiol in the postmenopausal range (26 IU/l) was associated with a longer time to bone as first recurrence (HR 0.66 95%CI: 0.41-1.04 p=0.072) compared to an FSH ≤26 IU/l. When all 3 hormone levels were within the assay specified postmenopausal range, a trend to improved IDFS was seen with addition of zoledronic acid in biochemically postmenopausal women only (postmenopausal HR=0.81; 95%CI: 0.54-1.22, non-postmenopausal HR=0.99; 95%CI: 0.69-1.39) with risk reductions that mirrored the results of the main AZURE study, although the interaction between menopausal status and treatment effect was not statistically significant (p=0.47). Oestradiol and FSH may influence the pattern of disease recurrence with postmenopausal levels possibly creating a less conducive environment for the formation of bone metastases, therefore disseminated tumour cells could seek

  4. Behavioral sexual dimorphism in school-age children and early developmental exposure to dioxins and PCBs: a follow-up study of the Duisburg Cohort.

    Science.gov (United States)

    Winneke, Gerhard; Ranft, Ulrich; Wittsiepe, Jürgen; Kasper-Sonnenberg, Monika; Fürst, Peter; Krämer, Ursula; Seitner, Gabriele; Wilhelm, Michael

    2014-03-01

    Polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and polychlorinated biphenyls (PCBs) are persistent organic pollutants that have been characterized as endocrine-disrupting chemicals (EDCs). Within the Duisburg birth cohort study, we studied associations of prenatal exposure to PCDD/Fs and PCBs with parent-reported sexually dimorphic behavior in children. We measured lipid-based and WHO2005-TEQ (toxic equivalents established in 2005 by the World Health Organization)-standardized PCDD/Fs and PCBs in maternal blood samples and in early breast milk using gas chromatography/high-resolution mass spectrometry. At the child's age of 6-8 years, parents (mostly mothers) reported sex-typical characteristics, preferred toys, and play activities using the Pre-School Activities Inventory (PSAI), which was used to derive feminine, masculine, and difference (feminine - masculine) scores. We estimated exposure-outcome associations using multivariate linear regression. A total of 91-109 children were included in this follow-up. Mean blood levels of summed WHO2005-TEQ-standardized dioxins (ΣPCDD/Fs) were 14.5 ± 6.4 pg/g blood lipids, and ΣPCBs were 6.9 ± 3.8 pg/g blood lipids, with similar values for milk lipids. Regression analyses revealed some highly significant interactions between sex and exposure-such as for ΣPCBs in milk, pronounced positive (boys: β = 3.24; CI = 1.35, 5.14) or negative (girls: β = -3.59; CI = -1.10, -6.08) associations with reported femininity. Less pronounced and mostly insignificant but consistent associations were found for the masculinity score, positive for boys and negative for girls. Given our results and the findings of previous studies, we conclude that there is sufficient evidence that these EDCs modify behavioral sexual dimorphism in children, presumably by interacting with the hypothalamic-pituitary-gonadal axis. Winneke G, Ranft U, Wittsiepe J, Kasper-Sonnenberg M, Fürst P, Krämer U, Seitner G, Wilhelm M. 2014. Behavioral

  5. A Novel Gonadotropin-Releasing Hormone 1 (Gnrh1 Enhancer-Derived Noncoding RNA Regulates Gnrh1 Gene Expression in GnRH Neuronal Cell Models.

    Directory of Open Access Journals (Sweden)

    Polly P Huang

    Full Text Available Gonadotropin-releasing hormone (GnRH, a neuropeptide released from a small population of neurons in the hypothalamus, is the central mediator of the hypothalamic-pituitary-gonadal axis, and is required for normal reproductive development and function. Evolutionarily conserved regulatory elements in the mouse, rat, and human Gnrh1 gene include three enhancers and the proximal promoter, which confer Gnrh1 gene expression specifically in GnRH neurons. In immortalized mouse hypothalamic GnRH (GT1-7 neurons, which show pulsatile GnRH release in culture, RNA sequencing and RT-qPCR revealed that expression of a novel long noncoding RNA at Gnrh1 enhancer 1 correlates with high levels of GnRH mRNA expression. In GT1-7 neurons, which contain a transgene carrying 3 kb of the rat Gnrh1 regulatory region, both the mouse and rat Gnrh1 enhancer-derived noncoding RNAs (GnRH-E1 RNAs are expressed. We investigated the characteristics and function of the endogenous mouse GnRH-E1 RNA. Strand-specific RT-PCR analysis of GnRH-E1 RNA in GT1-7 cells revealed GnRH-E1 RNAs that are transcribed in the sense and antisense directions from distinct 5' start sites, are 3' polyadenylated, and are over 2 kb in length. These RNAs are localized in the nucleus and have a half-life of over 8 hours. In GT1-7 neurons, siRNA knockdown of mouse GnRH-E1 RNA resulted in a significant decrease in the expression of the Gnrh1 primary transcript and Gnrh1 mRNA. Over-expression of either the sense or antisense mouse GnRH-E1 RNA in immature, migratory GnRH (GN11 neurons, which do not express either GnRH-E1 RNA or GnRH mRNA, induced the transcriptional activity of co-transfected rat Gnrh1 gene regulatory elements, where the induction requires the presence of the rat Gnrh1 promoter. Together, these data indicate that GnRH-E1 RNA is an inducer of Gnrh1 gene expression. GnRH-E1 RNA may play an important role in the development and maturation of GnRH neurons.

  6. A Novel Gonadotropin-Releasing Hormone 1 (Gnrh1) Enhancer-Derived Noncoding RNA Regulates Gnrh1 Gene Expression in GnRH Neuronal Cell Models.

    Science.gov (United States)

    Huang, Polly P; Brusman, Liza E; Iyer, Anita K; Webster, Nicholas J G; Mellon, Pamela L

    2016-01-01

    Gonadotropin-releasing hormone (GnRH), a neuropeptide released from a small population of neurons in the hypothalamus, is the central mediator of the hypothalamic-pituitary-gonadal axis, and is required for normal reproductive development and function. Evolutionarily conserved regulatory elements in the mouse, rat, and human Gnrh1 gene include three enhancers and the proximal promoter, which confer Gnrh1 gene expression specifically in GnRH neurons. In immortalized mouse hypothalamic GnRH (GT1-7) neurons, which show pulsatile GnRH release in culture, RNA sequencing and RT-qPCR revealed that expression of a novel long noncoding RNA at Gnrh1 enhancer 1 correlates with high levels of GnRH mRNA expression. In GT1-7 neurons, which contain a transgene carrying 3 kb of the rat Gnrh1 regulatory region, both the mouse and rat Gnrh1 enhancer-derived noncoding RNAs (GnRH-E1 RNAs) are expressed. We investigated the characteristics and function of the endogenous mouse GnRH-E1 RNA. Strand-specific RT-PCR analysis of GnRH-E1 RNA in GT1-7 cells revealed GnRH-E1 RNAs that are transcribed in the sense and antisense directions from distinct 5' start sites, are 3' polyadenylated, and are over 2 kb in length. These RNAs are localized in the nucleus and have a half-life of over 8 hours. In GT1-7 neurons, siRNA knockdown of mouse GnRH-E1 RNA resulted in a significant decrease in the expression of the Gnrh1 primary transcript and Gnrh1 mRNA. Over-expression of either the sense or antisense mouse GnRH-E1 RNA in immature, migratory GnRH (GN11) neurons, which do not express either GnRH-E1 RNA or GnRH mRNA, induced the transcriptional activity of co-transfected rat Gnrh1 gene regulatory elements, where the induction requires the presence of the rat Gnrh1 promoter. Together, these data indicate that GnRH-E1 RNA is an inducer of Gnrh1 gene expression. GnRH-E1 RNA may play an important role in the development and maturation of GnRH neurons.

  7. Current Concepts in Neuroendocrine Disruption

    Science.gov (United States)

    2014-01-01

    In the last few years, it has become clear that a wide variety of environmental contaminants have specific effects on neuroendocrine systems in fish, amphibians, birds and mammals. While it is beyond the scope of this review to provide a comprehensive examination of all of these neuroendocrine disruptors, we will focus on select representative examples. Organochlorine pesticides bioaccumulate in neuroendocrine areas of the brain that directly regulate GnRH neurons, thereby altering the expression of genes downstream of GnRH signaling. Organochlorine pesticides can also agonize or antagonize hormone receptors, adversely affecting crosstalk between neurotransmitter systems. The impacts of polychlorinated biphenyls are varied and in many cases subtle. This is particularly true for neuroedocrine and behavioral effects of exposure. These effects impact sexual differentiation of the hypothalamic-pituitary-gonadal axis, and other neuroendocrine systems regulating the thyroid, metabolic, and stress axes and their physiological responses. Weakly estrogenic and anti-androgenic pollutants such as bisphenol A, phthalates, phytochemicals, and the fungicide vinclozolin can lead to severe and widespread neuroendocrine disruptions in discrete brain regions, including the hippocampus, amygdala, and hypothalamus, resulting in behavioral changes in a wide range of species. Behavioral features that have been shown to be affected by one or more these chemicals include cognitive deficits, heightened anxiety or anxiety-like, sociosexual, locomotor, and appetitive behaviors. Neuroactive pharmaceuticals are now widely detected in aquatic environments and water supplies through the release of wastewater treatment plant effluents. The antidepressant fluoxetine is one such pharmaceutical neuroendocrine disruptor. Fluoxetine is a selective serotonin reuptake inhibitor that can affect multiple neuroendocrine pathways and behavioral circuits, including disruptive effects on reproduction and

  8. A Method for Modeling of Floating Vertical Axis Wind Turbine

    DEFF Research Database (Denmark)

    Wang, Kai; Hansen, Martin Otto Laver; Moan, Torgeir

    2013-01-01

    It is of interest to investigate the potential advantages of floating vertical axis wind turbine (FVAWT) due to its economical installation and maintenance. A novel 5MW vertical axis wind turbine concept with a Darrieus rotor mounted on a semi-submersible support structure is proposed in this paper....... In order to assess the technical and economic feasibility of this novel concept, a comprehensive simulation tool for modeling of the floating vertical axis wind turbine is needed. This work presents the development of a coupled method for modeling of the dynamics of a floating vertical axis wind turbine...

  9. Concept of a Programmable Fixture for 3-Axis CNC

    Directory of Open Access Journals (Sweden)

    Ahmad Dalloul

    2017-09-01

    Full Text Available CNC machine is the one of the major reasons for industrial advancement in recent decades for its ability of producing accurate parts. The most commen CNC machines are of 3-axis and adopted widely in the industrial sector. However, for producing more complicated parts 5-axis CNC machines are required. Although the introduction of the 5-axis machine came after the 3-axis CNC machine has established itself and many manufacturers did not make the move toward the newer model and its high pricing compared to the 3-axis model did not help either. In this time the development of a fixture or a platform to help transfer the 3-axis to a 5-axis to some degree. This paper discusses the concept of a programmable fixture that gives 3-axis CNC machine the freedom to act in similar manner as the 5-axis. The paper describes the mechanism with some initial results of the testing. Result showed that the platform moves in translation manner with an average error of 5.58 % and 7.303% average error for rotation movement.

  10. Suicidal behavior on Axis VI: clinical data supporting a sixth Axis for DSM-V.

    Science.gov (United States)

    Van Orden, Kimberly A; Witte, Tracy K; Holm-Denoma, Jill; Gordon, Kathryn H; Joiner, Thomas E

    2011-01-01

    Oquendo and colleagues (Oquendo, Baca-García, Mann, & Giner, 2008; Oquendo & Currier, 2009) recommend that DSM-V emphasize suicide risk assessment on a sixth axis, thereby increasing regularity of suicide risk assessments. We propose that evidence of nonredundancy with Axis V - Global Assessment of Functioning (GAF) is one piece of data that can serve as a starting point for a line of research establishing incremental predictive utility for a separate suicide risk assessment in the DSM framework. A standardized suicide risk assessment protocol, measures of depressive, anxious, and eating disordered symptomatology, as well as an index of comorbidity were administered to a sample of 412 adult outpatients. Our data indicate that data from standardized suicide risk assessments are associated with indices of symptomatology severity as well as comorbidity, controlling for GAF. These results support the nonredundancy of the assessments and suggest the utility of longitudinal investigations of the predictive utility of a sixth DSM axis in the assessment of suicide risk.

  11. Gut-Microbiota-Brain Axis and Its Effect on Neuropsychiatric Disorders With Suspected Immune Dysregulation.

    Science.gov (United States)

    Petra, Anastasia I; Panagiotidou, Smaro; Hatziagelaki, Erifili; Stewart, Julia M; Conti, Pio; Theoharides, Theoharis C

    2015-05-01

    Gut microbiota regulate intestinal function and health. However, mounting evidence indicates that they can also influence the immune and nervous systems and vice versa. This article reviews the bidirectional relationship between the gut microbiota and the brain, termed the microbiota-gut-brain (MGB) axis, and discusses how it contributes to the pathogenesis of certain disorders that may involve brain inflammation. Articles were identified with a search of Medline (starting in 1980) by using the key words anxiety, attention-deficit hypersensitivity disorder (ADHD), autism, cytokines, depression, gut, hypothalamic-pituitary-adrenal (HPA) axis, inflammation, immune system, microbiota, nervous system, neurologic, neurotransmitters, neuroimmune conditions, psychiatric, and stress. Various afferent or efferent pathways are involved in the MGB axis. Antibiotics, environmental and infectious agents, intestinal neurotransmitters/neuromodulators, sensory vagal fibers, cytokines, and essential metabolites all convey information to the central nervous system about the intestinal state. Conversely, the hypothalamic-pituitary-adrenal axis, the central nervous system regulatory areas of satiety, and neuropeptides released from sensory nerve fibers affect the gut microbiota composition directly or through nutrient availability. Such interactions seem to influence the pathogenesis of a number of disorders in which inflammation is implicated, such as mood disorder, autism-spectrum disorders, attention-deficit hypersensitivity disorder, multiple sclerosis, and obesity. Recognition of the relationship between the MGB axis and the neuroimmune systems provides a novel approach for better understanding and management of these disorders. Appropriate preventive measures early in life or corrective measures such as use of psychobiotics, fecal microbiota transplantation, and flavonoids are discussed. Copyright © 2015 Elsevier HS Journals, Inc. All rights reserved.

  12. Yaw dynamics of horizontal axis wind turbines

    Energy Technology Data Exchange (ETDEWEB)

    Hansen, A.C. (Utah Univ., Salt Lake City, UT (United States))

    1992-05-01

    Designers of a horizontal axis wind turbine yaw mechanism are faced with a difficult decision. They know that if they elect to use a yaw- controlled rotor then the system will suffer increased initial cost and increased inherent maintenance and reliability problems. On the other hand, if they elect to allow the rotor to freely yaw they known they will have to account for unknown and random, though bounded, yaw rates. They will have a higher-risk design to trade-off against the potential for cost savings and reliability improvement. The risk of a yaw-free system could be minimized if methods were available for analyzing and understanding yaw behavior. The complexity of yaw behavior has, until recently, discouraged engineers from developing a complete yaw analysis method. The objectives of this work are to (1) provide a fundamental understanding of free-yaw mechanics and the design concepts most effective at eliminating yaw problems, and (2) provide tested design tools and guidelines for use by free-yaw wind systems manufacturers. The emphasis is on developing practical and sufficiently accurate design methods.

  13. Microbiota and the gut-brain axis.

    Science.gov (United States)

    Bienenstock, John; Kunze, Wolfgang; Forsythe, Paul

    2015-08-01

    Changes in gut microbiota can modulate the peripheral and central nervous systems, resulting in altered brain functioning, and suggesting the existence of a microbiota gut-brain axis. Diet can also change the profile of gut microbiota and, thereby, behavior. Effects of bacteria on the nervous system cannot be disassociated from effects on the immune system since the two are in constant bidirectional communication. While the composition of the gut microbiota varies greatly among individuals, alterations to the balance and content of common gut microbes may affect the production of molecules such as neurotransmitters, e.g., gamma amino butyric acid, and the products of fermentation, e.g., the short chain fatty acids butyrate, propionate, and acetate. Short chain fatty acids, which are pleomorphic, especially butyrate, positively influence host metabolism by promoting glucose and energy homeostasis, regulating immune responses and epithelial cell growth, and promoting the functioning of the central and peripheral nervous systems. In the future, the composition, diversity, and function of specific probiotics, coupled with similar, more detailed knowledge about gut microbiota, will potentially help in developing more effective diet- and drug-based therapies. © The Author(s) 2015. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  14. Creating a Multi-axis Machining Postprocessor

    Directory of Open Access Journals (Sweden)

    Petr Vavruška

    2012-01-01

    Full Text Available This paper focuses on the postprocessor creation process. When using standard commercially available postprocessors it is often very difficult to modify its internal source code, and it is a very complex process, in many cases even impossible, to implement the newly-developed functions. It is therefore very important to have a method for creating a postprocessor for any CAM system, which allows CL data (Cutter Location data to be generated to a separate text file. The goal of our work is to verify the proposed method for creating a postprocessor. Postprocessor functions for multi-axis machiningare dealt with in this work. A file with CL data must be translated by the postprocessor into an NC program that has been customized for a specific production machine and its control system. The postprocessor is therefore verified by applications for machining free-form surfaces of complex parts, and by executing the NC programs that are generated on real machine tools. This is also presented here.

  15. Environmental Exposures and Neuropsychiatric Disorders: What Role Does the Gut-Immune-Brain Axis Play?

    Science.gov (United States)

    Delaney, Shannon; Hornig, Mady

    2018-02-08

    Evidence is growing that environmental exposures-including xenobiotics as well as microbes-play a role in the pathogenesis of many neuropsychiatric disorders. Underlying mechanisms are likely to be complex, involving the developmentally sensitive interplay of genetic/epigenetic, detoxification, and immune factors. Here, we review evidence supporting a role for environmental factors and disrupted gut-immune-brain axis function in some neuropsychiatric conditions. Studies suggesting the involvement of an altered microbiome in triggering CNS-directed autoimmunity and neuropsychiatric disturbances are presented as an intriguing example of the varied mechanisms by which environmentally induced gut-immune-brain axis dysfunction may contribute to adverse brain outcomes. The gut-immune-brain axis is a burgeoning frontier for investigation of neuropsychiatric illness. Future translational research to define individual responses to exogenous exposures in terms of microbiome-dependent skew of the metabolome, immunity, and brain function may serve as a lens for illumination of pathways involved in the development of CNS disease and fuel discovery of novel interventions.

  16. Mifepristone inhibits ovarian cancer metastasis by intervening in SDF-1/CXCR4 chemokine axis.

    Science.gov (United States)

    Zheng, Ning; Chen, Jiahang; Liu, Weiqun; Liu, Jian; Li, Tao; Chen, Hongning; Wang, Jichuang; Jia, Lee

    2017-08-29

    SDF-1/CXCR4 signaling axis determines the proliferative potential and site-specific cancer metastasis. Recent studies suggest involvement of the axis and steroidal hormone in ovarian cancer metastasis. Here we hypothesize that mifepristone (RU486), a well-known progesterone-based abortifacient, might interfere this axis and inhibit ovarian cancer metastasis. Mifepristone at concentrations SDF-1. SDF-1 significantly stimulated proliferation of SKOV-3 and IGROV-1 cells with concomitant increases in intracellular phosphorylation of Akt and ERK. SDF-1 activated cell chemotatic migration and actin polymerization, and up-regulated expression of MMP-2, MMP-9, COX-2, VEGF without influencing the adhesion molecules ICAM-1 and integrins β1, α1, α3, α5, and α6. The above-mentioned effects of SDF-1 could be antagonized by mifepristone concentration-dependently, and CXCR4 antagonist AMD3100. Mifepristone suppressed the SDF-1-induced migration, invasion and adhesion of the cancer cells to extracellular matrixes. Three-day pretreatment of nude mice with mifepristone (5 and 20 mg/kg/day) followed by a single intraperitoneal IGROV-1 inoculation, along with repeated SDF-1 and mifepristone administrations in turn every other day for 36 days significantly reduced ascitic fluid, metastatic foci, tumor weight and immunoreactivity of CXCR4 in comparison with the SDF-1-treated control. Our results suggest that mifepristone inhibit SDF-1/CXCR4 signaling axis, may have preventive and therapeutic effects on ovarian cancer metastasis.

  17. Spherical 3-Axis Hall Probe Array Calibration and Implementation for The Big Red Ball

    Science.gov (United States)

    Lynn, Jacob; E. Peterson Collaboration; D. Endrizzi Collaboration; M. Clark Collaboration; C. B. Forest Collaboration

    2017-10-01

    A 3-axis Helmholtz coil capable of producing 100 G magnetic fields at frequencies ranging from DC to 1 kHz has been built to calibrate an array of 3-axis hall probes. Accurate magnetic field measurements are necessary for diagnosing plasma equilibria and the presence of any MHD instabilities. The array will consist of three single-axis Hall sensors mounted orthogonally, each of which has a frequency response of 100 kHz and a sensitivity of 28mV/G. These probes will be placed on the inner surface of the machine to create a spherical array of sensors. Such an array will provide the necessary data to constrain plasma equilibrium parameters, such as current density and plasma pressure from ∇P = J × B . Understanding the plasma equilibrium, and large-scale magnetic fields is critical to understanding the dynamics involved in many phenomena, like the dynamo. Details on the design, calibration, and implementation of the three-axis Helmholtz coil and Hall sensors will be presented. DoE and NSF.

  18. Impact of Sleep and Its Disturbances on Hypothalamo-Pituitary-Adrenal Axis Activity

    Directory of Open Access Journals (Sweden)

    Marcella Balbo

    2010-01-01

    Full Text Available The daily rhythm of cortisol secretion is relatively stable and primarily under the influence of the circadian clock. Nevertheless, several other factors affect hypothalamo-pituitary-adrenal (HPA axis activity. Sleep has modest but clearly detectable modulatory effects on HPA axis activity. Sleep onset exerts an inhibitory effect on cortisol secretion while awakenings and sleep offset are accompanied by cortisol stimulation. During waking, an association between cortisol secretory bursts and indices of central arousal has also been detected. Abrupt shifts of the sleep period induce a profound disruption in the daily cortisol rhythm, while sleep deprivation and/or reduced sleep quality seem to result in a modest but functionally important activation of the axis. HPA hyperactivity is clearly associated with metabolic, cognitive and psychiatric disorders and could be involved in the well-documented associations between sleep disturbances and the risk of obesity, diabetes and cognitive dysfunction. Several clinical syndromes, such as insomnia, depression, Cushing's syndrome, sleep disordered breathing (SDB display HPA hyperactivity, disturbed sleep, psychiatric and metabolic impairments. Further research to delineate the functional links between sleep and HPA axis activity is needed to fully understand the pathophysiology of these syndromes and to develop adequate strategies of prevention and treatment.

  19. Axis: Generating Explanations at Scale with Learnersourcing and Machine Learning

    Science.gov (United States)

    Williams, Joseph Jay; Kim, Juho; Rafferty, Anna; Heffernan, Neil; Maldonado, Samuel; Gajos, Krzysztof Z.; Lasecki, Walter S.; Heffernan, Neil

    2016-01-01

    While explanations may help people learn by providing information about why an answer is correct, many problems on online platforms lack high-quality explanations. This paper presents AXIS (Adaptive eXplanation Improvement System), a system for obtaining explanations. AXIS asks learners to generate, revise, and evaluate explanations as they solve…

  20. A psychology of the human brain-gut-microbiome axis.

    Science.gov (United States)

    Allen, Andrew P; Dinan, Timothy G; Clarke, Gerard; Cryan, John F

    2017-04-01

    In recent years, we have seen increasing research within neuroscience and biopsychology on the interactions between the brain, the gastrointestinal tract, the bacteria within the gastrointestinal tract, and the bidirectional relationship between these systems: the brain-gut-microbiome axis. Although research has demonstrated that the gut microbiota can impact upon cognition and a variety of stress-related behaviours, including those relevant to anxiety and depression, we still do not know how this occurs. A deeper understanding of how psychological development as well as social and cultural factors impact upon the brain-gut-microbiome axis will contextualise the role of the axis in humans and inform psychological interventions that improve health within the brain-gut-microbiome axis. Interventions ostensibly aimed at ameliorating disorders in one part of the brain-gut-microbiome axis (e.g., psychotherapy for depression) may nonetheless impact upon other parts of the axis (e.g., microbiome composition and function), and functional gastrointestinal disorders such as irritable bowel syndrome represent a disorder of the axis, rather than an isolated problem either of psychology or of gastrointestinal function. The discipline of psychology needs to be cognisant of these interactions and can help to inform the future research agenda in this emerging field of research. In this review, we outline the role psychology has to play in understanding the brain-gut-microbiome axis, with a focus on human psychology and the use of research in laboratory animals to model human psychology.

  1. Angular momentum projection of tilted axis rotating states

    Energy Technology Data Exchange (ETDEWEB)

    Oi, M.; Onishi, N.; Tajima, N. [Tokyo Univ. (Japan); Horibata, T.

    1998-03-01

    We applied an exact angular momentum projection to three dimensional cranked HFB (3d-CHFB) states. Tilted axis rotating states (TAR) and principal axis rotating states (PAR) are compared. It is shown that TAR is more adequate than PAR for description of the back bending phenomena driven by tilted rotation or wobbling motion. (author)

  2. Dead-end tract of the conduction axis

    NARCIS (Netherlands)

    Kurosawa, H.; Becker, A. E.

    1985-01-01

    In the definitive heart the anterior continuation of the main conduction axis is considered to be the right bundle branch. In this study three hearts from neonates and infants were examined in which this situation did not pertain. The conduction axis continued beyond the point of origin of the right

  3. The Performance Characteristics of a Closed Loop, One Axis ...

    African Journals Online (AJOL)

    This paper presents a closed loop one axis solar tracking device of the polar axis type, which achieves an accurate tracking of the sun with a steady state error of less, than 2%. This prototype uses a photo-sensing system to generate an error signal. This error signal switches on a relay, which actuates an electromechanical ...

  4. Spin-stabilized magnetic levitation without vertical axis of rotation

    Science.gov (United States)

    Romero, Louis [Albuquerque, NM; Christenson, Todd [Albuquerque, NM; Aaronson, Gene [Albuquerque, NM

    2009-06-09

    The symmetry properties of a magnetic levitation arrangement are exploited to produce spin-stabilized magnetic levitation without aligning the rotational axis of the rotor with the direction of the force of gravity. The rotation of the rotor stabilizes perturbations directed parallel to the rotational axis.

  5. Investigation of blade performance of horizontal axis wind turbine ...

    African Journals Online (AJOL)

    The shape of rotor blade plays an important role in determining the overall aerodynamic performance of a horizontal axis wind turbine. In this work, blade is designed for a 5KW horizontal axis wind turbine which is already in market. For designing blade, blade element momentum theory (BEMT) is used and a computer ...

  6. A psychology of the human brain–gut–microbiome axis

    Science.gov (United States)

    Allen, Andrew P.; Dinan, Timothy G.; Clarke, Gerard

    2017-01-01

    Abstract In recent years, we have seen increasing research within neuroscience and biopsychology on the interactions between the brain, the gastrointestinal tract, the bacteria within the gastrointestinal tract, and the bidirectional relationship between these systems: the brain–gut–microbiome axis. Although research has demonstrated that the gut microbiota can impact upon cognition and a variety of stress‐related behaviours, including those relevant to anxiety and depression, we still do not know how this occurs. A deeper understanding of how psychological development as well as social and cultural factors impact upon the brain–gut–microbiome axis will contextualise the role of the axis in humans and inform psychological interventions that improve health within the brain–gut–microbiome axis. Interventions ostensibly aimed at ameliorating disorders in one part of the brain–gut–microbiome axis (e.g., psychotherapy for depression) may nonetheless impact upon other parts of the axis (e.g., microbiome composition and function), and functional gastrointestinal disorders such as irritable bowel syndrome represent a disorder of the axis, rather than an isolated problem either of psychology or of gastrointestinal function. The discipline of psychology needs to be cognisant of these interactions and can help to inform the future research agenda in this emerging field of research. In this review, we outline the role psychology has to play in understanding the brain–gut–microbiome axis, with a focus on human psychology and the use of research in laboratory animals to model human psychology. PMID:28804508

  7. Sequence-dependent rotation axis changes in tennis.

    Science.gov (United States)

    Hansen, Clint; Martin, Caroline; Rezzoug, Nasser; Gorce, Philippe; Bideau, Benoit; Isableu, Brice

    2017-09-01

    The purpose of this study was to evaluate the role of rotation axes during a tennis serve. A motion capture system was used to evaluate the contribution of the potential axes of rotation (minimum inertia axis, shoulder-centre of mass axis and the shoulder-elbow axis) during the four discrete tennis serve phases (loading, cocking, acceleration and follow through). Ten ranked athletes (International Tennis Number 1-3) repeatedly performed a flat service aiming at a target on the other side of the net. The four serve phases are distinct and thus, each movement phase seems to be organised around specific rotation axes. The results showed that the limbs' rotational axis does not necessarily coincide with the minimum inertia axis across the cocking phase of the tennis serve. Even though individual serving strategies were exposed, all participants showed an effect due to the cocking phase and changed the rotation axis during the task. Taken together, the results showed that despite inter-individual differences, nine out of 10 participants changed the rotation axis towards the minimum inertia and/or the mass axis in an endeavour to maximise external rotation of the shoulder to optimally prepare for the acceleration phase.

  8. The Hypothalamic–Pituitary Axis and Autoantibody Related Disorders

    Directory of Open Access Journals (Sweden)

    Cristina Cocco

    2017-11-01

    Full Text Available This review summarized different studies reporting the presence of autoantibodies reacting against cells of the pituitary (APAs and/or hypothalamus (AHAs. Both APAs and AHAs have been revealed through immunofluorescence using different kinds of substrates. Autoantibodies against gonadotropic cells were mainly found in patients affected by cryptorchidism and hypogonadotropic hypogonadism while those against prolactin cells were found in different kinds of patients, the majority without pituitary abnormalities. APAs to growth hormone (GH cells have been associated with GH deficiency while those against the adrenocorticotropic cells have distinguished central Cushing’s disease patients at risk of incomplete cure after surgical adenoma removal. AHAs to vasopressin cells have identified patients at risk of developing diabetes insipidus. APAs have been also found together with AHAs in patients affected by idiopathic hypopituitarism, but both were also present in different kinds of patients without abnormalities of the hypothalamic–pituitary axis. Despite some data being promising, the clinical use of pituitary and hypothalamus autoantibodies is still limited by the low diagnostic sensitivity, irreproducibility of the results, and the absence of autoantigen/s able to discriminate the autoimmune reaction involving the pituitary or the hypothalamus from the other autoimmune states.

  9. Analytic representation of electron central-axis depth dose data

    International Nuclear Information System (INIS)

    Jette, D.; Lanzl, L.H.; Rozenfeld, M.; Pagnamenta, A.

    1981-01-01

    We have examined a number of analytic representations of electron central-axis depth dose data current in the literature, testing them against sets of standard depth dose data. One of them, a two-parameter model of Shabason and Hendee, is recommended in situations in which good accuracy (approximately 2%) is desired, with the values of the parameters determined by an approximation formula which we have developed elsewhere. For higher accuracy, we have developed a polynomial model which gives, typically, a standard deviation of the fitting polynomial from the data points of 1%, and a maximum deviation of 2%. Fitting polynomials obtained with this method possess the property of having zero slope at the position of actual maximum dose, and generally a fifth-order polynomial (requiring four nonzero coefficients) provided the most acceptable fit. The four parameters involved are determined through inversion of a 4 x 4 matrix, and we have tabulated these four coefficients for the standard data sets. The polynomial model is designed for interpolation in the range between the 100% dose depth and the 10% dose depth, and another fitting curve of the same type can be adjoined to cover depths less than the 100% dose depth

  10. Role of Incretin Axis in Inflammatory Bowel Disease

    Directory of Open Access Journals (Sweden)

    Lihua Duan

    2017-12-01

    Full Text Available The inflammatory bowel diseases (IBDs, including Crohn’s disease (CD and ulcerative colitis (UC, are chronic inflammatory conditions of the gastrointestinal tract and involve a complicated reciprocity of environmental, genetic, and immunologic factors. Despite substantial advances in the foundational understanding of the immunological pathogenesis of IBD, the detailed mechanism of the pathological progression in IBD remains unknown. In addition to Th1/Th2 cells, whose role in IBD has been previously well defined, recent evidence indicates that Th17 cells and Tregs also play a crucial role in the development of IBD. Diets which contain excess sugars, salt, and fat may also be important actors in the pathogenesis of IBD, which may be the cause of high IBD incidence in western developed and industrialized countries. Up until now, the reason for the variance in prevalence of IBD between developed and developing countries has been unknown. This is partly due to the increasing popularity of western diets in developing countries, which makes the data harder to interpret. The enterocrinins glucagon-like peptides (GLPs, including GLP-1 and GLP-2, exhibit notable benefits on lipid metabolism, atherosclerosis formation, plasma glucose levels, and maintenance of gastric mucosa integrity. In addition to the regulation of nutrient metabolism, the emerging role of GLPs and their degrading enzyme dipeptidyl peptidase-4 (DPP-4 in gastrointestinal diseases has gained increasing attention. Therefore, here we review the function of the DPP-4/GLP axis in IBD.

  11. Prevalence and comorbidity of Axis I and Axis II disorders among treatment refractory adolescents admitted for specialized psychotherapy

    NARCIS (Netherlands)

    Feenstra, D.J.; Busschbach, J.J.V.; Verheul, R.; Hutsebaut, J.

    2011-01-01

    Research shows that approximately half of the adolescents in a clinical setting suffer from a personality disorder (PD). This finding has not yet been replicated in Europe. To test whether this finding also applies to Europe, structured diagnostic interviews for both Axis I and Axis II disorders

  12. Stress and serial adult metamorphosis: Multiple roles for the stress axis in socially regulated sex change

    Directory of Open Access Journals (Sweden)

    Tessa K Solomon-Lane

    2013-11-01

    Full Text Available Socially regulated sex change in teleost fishes is a striking example of social status information regulating biological function in the service of reproductive success. The establishment of social dominance in sex changing species is translated into a cascade of changes in behavior, physiology, neuroendocrine function, and morphology that transforms a female into a male, or vice versa. The hypothalamic-pituitary-interrenal axis (HPI, homologous to HP-adrenal axis in mammals and birds has been hypothesized to play a mechanistic role linking status to sex change. The HPA/I axis responds to environmental stressors by integrating relevant external and internal cues and coordinating biological responses including changes in behavior, energetics, physiology, and morphology (i.e., metamorphosis. Through actions of both corticotropin-releasing factor and glucocorticoids (GCs, the HPA/I axis has been implicated in processes central to sex change, including the regulation of agonistic behavior, social status, energetic investment, and life history transitions. In this paper, we review the hypothesized roles of the HPA/I axis in the regulation of sex change and how those hypotheses have been tested to date. We include original data on sex change in the bluebanded goby (Lythyrpnus dalli, a highly social fish capable of bidirectional sex change. We then propose a model for HPA/I involvement in sex change and discuss how these ideas might be tested in the future. Understanding the regulation of sex change has the potential to elucidate evolutionarily conserved mechanisms responsible for translating pertinent information about the environment into coordinated biological changes along multiple body axes.

  13. [Localization and registration of the hinge axis in black Africans].

    Science.gov (United States)

    Assi, K D; N'Guessan, K S; N'Dindin, C; Bamba, A

    2003-06-01

    The study of the cinematic method using "SAM" and "Quick Axis of FAG" added to mandibular condyle palpation for the hinge axis limited points, show that the Black Africans mandibular condyle rotation axis position is higher (3.5 mm) and backer (2 mm) than the Caucasians. The axial points are located to between 11 and 12 mm in front of the tragus and between 7 and 8 mm below on the perpendicular line to the furrow defining the tragus superior side to the Ectocanthus.

  14. Thoughts on the so-called radius-capitellum axis

    Energy Technology Data Exchange (ETDEWEB)

    Schild, H.; Mueller, H.A.; Wagner, H.; Baetz, W.

    1982-02-01

    We have studied 438 patients radiologically in order to observe the so-called 'radius-capitellum axis'. In about a quarter of people with normal elbows the axis passes lateral to the middle portion of the capitellum, so that even when there is marked deviation, there is no certainty that the humero-radial joint is abnormal. Deviation of the axis can be caused by changes in the shape of the capitellum or of the radius, or by distension of the capsule of the elbow joint, or by various changes in muscular pull.

  15. Multi-Axis Force/Torque Sensor Based on Simply-Supported Beam and Optoelectronics.

    Science.gov (United States)

    Noh, Yohan; Bimbo, Joao; Sareh, Sina; Wurdemann, Helge; Fraś, Jan; Chathuranga, Damith Suresh; Liu, Hongbin; Housden, James; Althoefer, Kaspar; Rhode, Kawal

    2016-11-17

    This paper presents a multi-axis force/torque sensor based on simply-supported beam and optoelectronic technology. The sensor's main advantages are: (1) Low power consumption; (2) low-level noise in comparison with conventional methods of force sensing (e.g., using strain gauges); (3) the ability to be embedded into different mechanical structures; (4) miniaturisation; (5) simple manufacture and customisation to fit a wide-range of robot systems; and (6) low-cost fabrication and assembly of sensor structure. For these reasons, the proposed multi-axis force/torque sensor can be used in a wide range of application areas including medical robotics, manufacturing, and areas involving human-robot interaction. This paper shows the application of our concept of a force/torque sensor to flexible continuum manipulators: A cylindrical MIS (Minimally Invasive Surgery) robot, and includes its design, fabrication, and evaluation tests.

  16. Multi-Axis Force/Torque Sensor Based on Simply-Supported Beam and Optoelectronics

    Directory of Open Access Journals (Sweden)

    Yohan Noh

    2016-11-01

    Full Text Available This paper presents a multi-axis force/torque sensor based on simply-supported beam and optoelectronic technology. The sensor’s main advantages are: (1 Low power consumption; (2 low-level noise in comparison with conventional methods of force sensing (e.g., using strain gauges; (3 the ability to be embedded into different mechanical structures; (4 miniaturisation; (5 simple manufacture and customisation to fit a wide-range of robot systems; and (6 low-cost fabrication and assembly of sensor structure. For these reasons, the proposed multi-axis force/torque sensor can be used in a wide range of application areas including medical robotics, manufacturing, and areas involving human–robot interaction. This paper shows the application of our concept of a force/torque sensor to flexible continuum manipulators: A cylindrical MIS (Minimally Invasive Surgery robot, and includes its design, fabrication, and evaluation tests.

  17. Role of the Orexin System on the Hypothalamus-Pituitary-Thyroid Axis

    Science.gov (United States)

    Messina, Antonietta; De Fusco, Carolina; Monda, Vincenzo; Esposito, Maria; Moscatelli, Fiorenzo; Valenzano, Anna; Carotenuto, Marco; Viggiano, Emanuela; Chieffi, Sergio; De Luca, Vincenzo; Cibelli, Giuseppe; Monda, Marcellino; Messina, Giovanni

    2016-01-01

    Hypocretin/orexin (ORX) are two hypothalamic neuropeptides discovered in 1998. Since their discovery, they have been one of the most studied neuropeptide systems because of their projecting fields innervating various brain areas. The orexinergic system is tied to sleep-wakefulness cycle, and narcolepsy is a consequence of their system hypofunction. Orexinergic system is also involved in many other autonomic functions such as feeding, thermoregulation, cardiovascular and neuroendocrine regulation. The main aim of this mini review article is to investigate the relationship between ORX and thyroid system regulation. Although knowledge about the ORX system is evolving, its putative effects on hypothalamic-pituitary-thyroid (HPT) axis still appear unclear. We analyzed some studies about ORX control of HPT axis to know better the relationship between them. The studies that were analyzed suggest Hypocretin/ORX to modulate the thyroid regulation, but the nature (excitatory or inhibitory) of this possible interaction remains actually unclear and needs to be confirmed. PMID:27610076

  18. Patient specific modeling of the HPA axis related to clinical diagnosis of depression

    DEFF Research Database (Denmark)

    Bangsgaard, Elisabeth; Ottesen, Johnny T.

    2017-01-01

    A novel model of the hypothalamic-pituitary-adrenal axis is presented. The axis is an endocrine system responsible for coping with stress and it is likely to be involved in depression. The dynamics of the system is studied and existence, uniqueness and positivity of the solution and the existence...... of an attracting trapping region are proved. The model is calibrated and compared to data for healthy and depressed subjects. A sensitivity analysis resulting in a set of identifiable physiological parameters is provided. A subset is selected for parameter estimation and a reduced version of the model is stated...... method for diagnosing depression and suggesting individual treatment protocols. Finally, the method may inspire pharmaceutical companies to develop target specific psychopharmaca for more effective and individual treatment....

  19. Conceptual Design of a Floating Support Structure and Mooring System for a Vertical Axis Wind Turbine

    DEFF Research Database (Denmark)

    Berthelsen, Petter Andreas; Fylling, Ivar; Vita, Luca

    2012-01-01

    This paper deals with the conceptual design of a floating support structure and mooring system for a 5MW vertical axis offshore wind turbine. The work is carried out as part of the DeepWind project, where the main objective is to investigate the feasibility of a floating vertical axis offshore wind...... turbine. The DeepWind concept consists of a Darrieus rotor mounted on a spar buoy support structure. The conceptual design is carried out in an iterative process, involving the different subcomponents. The present work is part of the first design iteration and the objective is to find a feasible floating...... support structure and mooring system for the DeepWind concept. The conceptual design is formulated as an optimization problem: Starting with an initial configuration, the optimization procedure tries to find a cheaper solution while satisfying a set of design requirements. This approach utilizes available...

  20. Maternal separation as a model of brain-gut axis dysfunction.

    LENUS (Irish Health Repository)

    O'Mahony, Siobhain M

    2011-03-01

    Early life stress has been implicated in many psychiatric disorders ranging from depression to anxiety. Maternal separation in rodents is a well-studied model of early life stress. However, stress during this critical period also induces alterations in many systems throughout the body. Thus, a variety of other disorders that are associated with adverse early life events are often comorbid with psychiatric illnesses, suggesting a common underlying aetiology. Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder that is thought to involve a dysfunctional interaction between the brain and the gut. Essential aspects of the brain-gut axis include spinal pathways, the hypothalamic pituitary adrenal axis, the immune system, as well as the enteric microbiota. Accumulating evidence suggest that stress, especially in early life, is a predisposing factor to IBS.

  1. Rates and processes of crystallization in on-axis and off-axis MOR basaltic melts

    Science.gov (United States)

    Zellmer, Georg F.; Dulski, Peter; Iizuka, Yoshiyuki; Perfit, Michael R.

    2012-12-01

    Residence times of olivine and plagioclase phenocrysts and xenocrysts in mid-ocean ridge (MOR) basaltic melts have been studied since the mid 1980s using geospeedometric techniques (i.e. using diffusion of major and trace elements) in order to constrain the processes of melt ascent and differentiation in this important magmatic setting. Residence times range from a few hours to several years, but potential links between these timescales and specific tectonomagmatic variables such as spreading rate and relative locations of eruption site and ridge axis have remained elusive. Here we demonstrate how incomplete chemical diffusion of Sr within plagioclase crystals from MOR basalts erupted in on- and off-axis settings on a number of ridges with variable spreading rates provide geospeedometric constraints. We combine electron probe microanalytical crystal maps with detailed laser ablation profiles of almost 70 plagioclase crystals from the fast spreading East Pacific Rise (EPR) at 9-10°N, the intermediate spreading Gorda and Juan de Fuca (JdF) ridges, and the ultraslow spreading Gakkel ridge to calculate crystal residence times. These range from a few days to several months. The scarcity of residence times exceeding years corroborates previous data indicating that most of the growth of plagioclase phenocrysts occurs within the conduit at the onset of and during eruption on the sea floor, and extends this result to the fast-spreading EPR. Further, statistical analysis is employed to show for the first time that residence times are systematically longer at slower spreading rates, in off-axis samples, and samples sourced from laterally distal axial melt lenses. Plagioclase textures and residence time variations appear to be linked to differences in the dynamics of late-stage, pre-eruptive magma storage and ascent in the different tectonomagmatic settings investigated. In the future, geospeedometric work on MOR samples will be required to assess if the effect of spreading

  2. Design characteristics to reduce inadvertent cross-axis coupling during side stick handling of aircraft pitch and roll axis control

    Science.gov (United States)

    Cote, Marie-Eve

    Integrating a manual flight control inceptor with coupled axes such as the side stick within a flight deck creates challenges for the pilot to input a one-axis command without inadvertently inducing inputs in the opposite axis. The present paper studies three design features of the side stick and armrest setup believed to help reduce inadvertent cross-axis coupling occurrences. Design features address the aimed pilot population anthropometry (1.57m woman to 1.9m male) and their variability in upper segment measurements. Seven pilots of varying anthropometric sizes were asked to perform one-axis manoeuvres in pitch and roll for each setup configuration. To compare the setups both the duration and the definite integral of the unintended cross-axis input were processed and analyzed for each manoeuvre. Findings show that a short armrest reduces the occurrences of cross-axis input for the roll manoeuvre, whereas the side stick skew reduces inadvertent cross-axis coupling for the pitch manoeuvres.

  3. Disruptive physiology: olfaction and the microbiome-gut-brain axis.

    Science.gov (United States)

    Bienenstock, John; Kunze, Wolfgang A; Forsythe, Paul

    2018-02-01

    This review covers the field of olfaction and chemosensation of odorants and puts this information into the context of interactions between microbes and behaviour; the microbiome-gut-brain axis (MGBA). Recent emphasis has also been placed on the concept of the holobiome which states that no single aspect of an organism should be viewed separately and thus must include examination of their associated microbial populations and their influence. While it is known that the microbiome may be involved in the modulation of animal behaviour, there has been little systematized effort to incorporate into such studies the rapidly developing knowledge of the wide range of olfactory systems. The classical olfactory system is evolutionarily conserved in multiple taxa from insects through to fish, reptiles and mammals, and is represented by the largest gene families in vertebrates. Mice have over 1000 different olfactory receptors and humans about 400. They are distributed throughout the body and are even found in spermatozoa where they function in chemotaxis. Each olfactory receptor has the unique functional capability of high-affinity binding to several different molecular ligands. These and other properties render the cataloguing of odorants (odorome) with specific actions a difficult task. Some ectopic olfactory receptors have been shown to have functional effects in the gut and kidney, highlighting the complexity of the systems engaged by odorants. However, there are, in addition to classical olfactory receptors, at least two other families of receptors involved in olfaction that are also widely found expressed on tissues in many different organs in addition to the nervous system and brain: the trace-amine associated and formyl peptide receptors. Bacteria can make many if not most odorants and are responsible for recognition of species and relative relatedness, as well as predator presence, among many other examples. Activation of different combinations of olfactory receptors

  4. Particle orbit analysis for LHD helical axis configurations

    International Nuclear Information System (INIS)

    Guasp, J.; Yamazaki, K.; Motojima, O.

    1993-04-01

    Fast ion orbits for helical magnetic axis configurations in LHD (Large Helical Device) are analyzed and compared with the standard circular axis case. Boundaries between passing and helically trapped particle regions show clear differences: in the non-planar axis case the helically trapped region spreads, near the magnetic axis, over a much wider band across the 90deg pitch angle value and shows a very marked asymmetry. The locally trapped particle region is also wider than in the standard case. The differences in the loss cone boundaries of the two cases are rather small, however, the effects of re-entering criteria are very important in both cases. On the contrary, effects of finite coil size are not significant. (author)

  5. Tilted-axis wobbling in odd-mass nuclei

    Science.gov (United States)

    Budaca, R.

    2018-02-01

    A triaxial rotor Hamiltonian with a rigidly aligned high-j quasiparticle is treated by a time-dependent variational principle, using angular momentum coherent states. The resulting classical energy function has three unique critical points in a space of generalized conjugate coordinates, which can minimize the energy for specific ordering of the inertial parameters and a fixed angular momentum state. Because of the symmetry of the problem, there are only two unique solutions, corresponding to wobbling motion around a principal axis and, respectively, a tilted axis. The wobbling frequencies are obtained after a quantization procedure and then used to calculate E 2 and M 1 transition probabilities. The analytical results are employed in the study of the wobbling excitations of 135Pr nucleus, which is found to undergo a transition from low angular momentum transverse wobbling around a principal axis toward a tilted-axis wobbling at higher angular momentum.

  6. Off-axis vortex breakdown in a shallow whirlpool.

    Science.gov (United States)

    Herrada, Miguel A; Shtern, Vladimir N; López-Herrera, José María

    2013-06-01

    The off-axis emergence of vortex breakdown (VB) is revealed. The steady axisymmetric flow in a vertical sealed cylinder, which is partially filled with water and the rest is filled with air, is driven by the rotating bottom disk. The numerical simulations show that VB can emerge away from the rotation axis, interface, and walls. As the rotation intensifies, VB first develops in the water region. If the water height is less (larger) than nearly one half of the cylinder radius, VB emerges off (on) the axis. As the rotation further increases, the off-axis VB ring touches the interface and then a thin countercirculation layer develops in the air flow above the water VB domain. This two-fluid VB ring shrinks (it even disappears in a very shallow whirlpool) as the interface approaches the bottom disk.

  7. Space/Flight Operable Miniature Six Axis Transducer, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — FUTEK will fully design and manufacture a sensor capable of measuring forces in and about each axis. The unit will measure forces up to 300 Newton's in the principle...

  8. The effects of lateral head tilt on ocular astigmatic axis

    Directory of Open Access Journals (Sweden)

    Hamid Fesharaki

    2014-01-01

    Conclusion: Any minimal angle of head tilt may cause erroneous measurement of astigmatic axis and should be avoided during refraction. One cannot rely on the compensatory function of ocular counter-torsion during the refraction.

  9. Determination of Elastic Twist in Horizontal Axis Wind Turbines (HAWTs)

    Energy Technology Data Exchange (ETDEWEB)

    Stoddard, F.; Nelson, V.; Starcher, K.; Andrews, B.

    2006-06-01

    This report presents the results of a project at the Alternative Energy Institute (AEI) which measured and calculated the elastic twist of three representative composite horizontal-axis blades: Carter 300, Gougeon ESI 54, and UTRC 8 kW.

  10. UARS PEM Level 2 AXIS 1 V001

    Data.gov (United States)

    National Aeronautics and Space Administration — The UARS Particle Environment Monitor (PEM) level 2 Atmosphere X-Ray Imaging Spectrometer (AXIS) unit 1 daily product contains the X-ray high-resolution spectral...

  11. UARS PEM Level 2 AXIS 2 V001

    Data.gov (United States)

    National Aeronautics and Space Administration — The UARS Particle Environment Monitor (PEM) level 2 Atmosphere X-Ray Imaging Spectrometer (AXIS) unit 2 daily product contains the X-ray high-resolution spectral...

  12. Design of a Three-Axis Machine Tool Module

    National Research Council Canada - National Science Library

    Childers, Marshal

    2003-01-01

    This report documents the design improvement process of the components in a tool module for a three-axis machine tool, which occurred during the period of March-April 2002 in support of a critical U.S...

  13. Stress and the HPA Axis: Balancing Homeostasis and Fertility

    Directory of Open Access Journals (Sweden)

    Dana N. Joseph

    2017-10-01

    Full Text Available An organism’s reproductive fitness is sensitive to the environment, integrating cues of resource availability, ecological factors, and hazards within its habitat. Events that challenge the environment of an organism activate the central stress response system, which is primarily mediated by the hypothalamic–pituitary–adrenal (HPA axis. The regulatory functions of the HPA axis govern the cardiovascular and metabolic system, immune functions, behavior, and reproduction. Activation of the HPA axis by various stressors primarily inhibits reproductive function and is able to alter fetal development, imparting a biological record of stress experienced in utero. Clinical studies and experimental data indicate that stress signaling can mediate these effects through direct actions in the brain, gonads, and embryonic tissues. This review focuses on the mechanisms by which stress activation of the HPA axis impacts fertility and fetal development.

  14. Stress and the HPA Axis: Balancing Homeostasis and Fertility.

    Science.gov (United States)

    Joseph, Dana N; Whirledge, Shannon

    2017-10-24

    An organism's reproductive fitness is sensitive to the environment, integrating cues of resource availability, ecological factors, and hazards within its habitat. Events that challenge the environment of an organism activate the central stress response system, which is primarily mediated by the hypothalamic-pituitary-adrenal (HPA) axis. The regulatory functions of the HPA axis govern the cardiovascular and metabolic system, immune functions, behavior, and reproduction. Activation of the HPA axis by various stressors primarily inhibits reproductive function and is able to alter fetal development, imparting a biological record of stress experienced in utero. Clinical studies and experimental data indicate that stress signaling can mediate these effects through direct actions in the brain, gonads, and embryonic tissues. This review focuses on the mechanisms by which stress activation of the HPA axis impacts fertility and fetal development.

  15. Dual Axis Controller for Extreme Environments, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — The Dual Axis Controller for Extreme Environments (DACEE) addresses a critical need of NASA's future exploration plans to investigate extreme environments within our...

  16. Three-Axis Gasless Sounding Rocket Payload Attitude Control

    Data.gov (United States)

    National Aeronautics and Space Administration — Gas released by current sounding rocket payload attitude control systems (ACS) has the potential to interfere with some types of science instruments. A single-axis...

  17. Early programming of the IGF-I axis

    DEFF Research Database (Denmark)

    Larnkjær, Anni; Ingstrup, Helga Kristensen; Schack-Nielsen, Lene

    2009-01-01

    -I production. Conversely, studies suggest that later in childhood, those breastfed are taller and have higher IGF-I levels. Therefore, it has been suggested that the IGF-I axis may be programmed by diet during infancy. The association between IGF-I in infancy and later life is not known. OBJECTIVE: To examine......=-0.26, P=0.043, and n=109). CONCLUSION: The results support the hypothesis that the IGF-I axis can be programmed early in life....

  18. Comparison of astigmatic axis in the seated and supine positions.

    Science.gov (United States)

    Smith, E M; Talamo, J H; Assil, K K; Petashnick, D E

    1994-01-01

    Refractive error is assessed in the seated position while keratorefractive procedures are performed in the supine position. Since position-induced ocular torsion could yield suboptimal results from improper axis alignment, this study was undertaken to ascertain whether ocular cyclotorsion occurs when a subject moves from a seated to supine position. Fifty eyes of 29 subjects with refractive cylinder greater than 0.50 diopters were enrolled. Refraction was done with a phoropter and the correction was placed in a trial frame using plus cylinder. Astigmatic axis was determined in the seated and supine positions for 32 eyes by utilizing the "rocking the cylinder" technique and for 32 eyes using the Jackson cross cylinder. Both techniques were used for 14 eyes. No statistically-significant difference for cylinder axis measured in the seated versus supine position was observed using the rocking the cylinder (4.3 degrees standard deviation [SD], 3.5 degrees, range 0 degrees to 13 degrees, p = NS) or the Jackson cross cylinder methods (2.3 degrees, SD, 1.9 degrees, range 0 degrees to 7 degrees, p = NS). Approximately 25% of eyes had a change in axis of 7 degrees to 16 degrees. These data suggest that the cylinder axis does not change significantly or predictably when most subjects move from the seated to supine position. The Jackson cross cylinder method seems more accurate and reproducible than the rocking the cylinder technique in determination of astigmatic axis under these circumstances.

  19. Design and optimize of 3-axis filament winding machine

    Science.gov (United States)

    Quanjin, Ma; Rejab, M. R. M.; Idris, M. S.; Bachtiar, B.; Siregar, J. P.; Harith, M. N.

    2017-10-01

    Filament winding technique is developed as the primary process for composite cylindrical structures fabrication at low cost. Fibres are wound on a rotating mandrel by a filament winding machine where resin impregnated fibres pass through a pay-out eye. This paper aims to develop and optimize a 3-axis, lightweight, practical, efficient, portable filament winding machine to satisfy the customer demand, which can fabricate pipes and round shape cylinders with resins. There are 3 main units on the 3-axis filament winding machine, which are the rotary unit, the delivery unit and control system unit. Comparison with previous existing filament winding machines in the factory, it has 3 degrees of freedom and can fabricate more complex shape specimens based on the mandrel shape and particular control system. The machine has been designed and fabricated on 3 axes movements with control system. The x-axis is for movement of the carriage, the y-axis is the rotation of mandrel and the z-axis is the movement of the pay-out eye. Cylindrical specimens with different dimensions and winding angles were produced. 3-axis automated filament winding machine has been successfully designed with simple control system.

  20. Self-starting aerodynamics analysis of vertical axis wind turbine

    Directory of Open Access Journals (Sweden)

    Jianyang Zhu

    2015-12-01

    Full Text Available Vertical axis wind turbine is a special type of wind-force electric generator which is capable of working in the complicated wind environment. The self-starting aerodynamics is one of the most important considerations for this kind of turbine. This article aims at providing a systematic synthesis on the self-starting aerodynamic characteristics of vertical axis wind turbine based on the numerical analysis approach. First, the physical model of vertical axis wind turbine and its parameter definitions are presented. Secondary, the interaction model between the vertical axis wind turbine and fluid is developed by using the weak coupling approach; the numerical data of this model are then compared with the wind tunnel experimental data to show its feasibility. Third, the effects of solidity and fixed pitch angle on the self-starting aerodynamic characteristics of the vertical axis wind turbine are analyzed systematically. Finally, the quantification effects of the solidity and fixed pitch angle on the self-starting performance of the turbine can be obtained. The analysis in this study will provide straightforward physical insight into the self-starting aerodynamic characteristics of vertical axis wind turbine.

  1. Energy Efficient Hybrid Dual Axis Solar Tracking System

    Directory of Open Access Journals (Sweden)

    Rashid Ahammed Ferdaus

    2014-01-01

    Full Text Available This paper describes the design and implementation of an energy efficient solar tracking system from a normal mechanical single axis to a hybrid dual axis. For optimizing the solar tracking mechanism electromechanical systems were evolved through implementation of different evolutional algorithms and methodologies. To present the tracker, a hybrid dual-axis solar tracking system is designed, built, and tested based on both the solar map and light sensor based continuous tracking mechanism. These light sensors also compare the darkness and cloudy and sunny conditions assisting daily tracking. The designed tracker can track sun’s apparent position at different months and seasons; thereby the electrical controlling device requires a real time clock device for guiding the tracking system in seeking solar position for the seasonal motion. So the combination of both of these tracking mechanisms made the designed tracker a hybrid one. The power gain and system power consumption are compared with a static and continuous dual axis solar tracking system. It is found that power gain of hybrid dual axis solar tracking system is almost equal to continuous dual axis solar tracking system, whereas the power saved in system operation by the hybrid tracker is 44.44% compared to the continuous tracking system.

  2. The Gut-Brain Axis, BDNF, NMDA and CNS Disorders.

    Science.gov (United States)

    Maqsood, Raeesah; Stone, Trevor W

    2016-11-01

    Gastro-intestinal (GI) microbiota and the 'gut-brain axis' are proving to be increasingly relevant to early brain development and the emergence of psychiatric disorders. This review focuses on the influence of the GI tract on Brain-Derived Neurotrophic Factor (BDNF) and its relationship with receptors for N-methyl-D-aspartate (NMDAR), as these are believed to be involved in synaptic plasticity and cognitive function. NMDAR may be associated with the development of schizophrenia and a range of other psychopathologies including neurodegenerative disorders, depression and dementias. An analysis of the routes and mechanisms by which the GI microbiota contribute to the pathophysiology of BDNF-induced NMDAR dysfunction could yield new insights relevant to developing novel therapeutics for schizophrenia and related disorders. In the absence of GI microbes, central BDNF levels are reduced and this inhibits the maintenance of NMDAR production. A reduction of NMDAR input onto GABA inhibitory interneurons causes disinhibition of glutamatergic output which disrupts the central signal-to-noise ratio and leads to aberrant synaptic behaviour and cognitive deficits. Gut microbiota can modulate BDNF function in the CNS, via changes in neurotransmitter function by affecting modulatory mechanisms such as the kynurenine pathway, or by changes in the availability and actions of short chain fatty acids (SCFAs) in the brain. Interrupting these cycles by inducing changes in the gut microbiota using probiotics, prebiotics or antimicrobial drugs has been found promising as a preventative or therapeutic measure to counteract behavioural deficits and these may be useful to supplement the actions of drugs in the treatment of CNS disorders.

  3. Design Of Single-Axis And Dual-Axis Solar Tracking Systems Protected Against High Wind Speeds

    Directory of Open Access Journals (Sweden)

    Mai Salaheldin Elsherbiny

    2017-09-01

    Full Text Available Solar energy is rapidly gaining ground as an important mean of expanding renewable energy use. Solar tracking is employed in order to maximize collected solar radiation by a photovoltaic panel. In this paper we present a prototype for Automatic solar tracker that is designed using Arduino UNO with Wind sensor to Cease Wind effect on panels if wind speed exceeds certain threshold. The Proposed solar tracker tracks the location of the sun anywhere in any time by calculating the position of the sun. For producing the maximum amount of solar energy a solar panel must always be perpendicular to the source of light. Because the sun motion plane varies daily and during the day it moves from east to west one needs two axis tracking to follow the suns position. Maximum possible power is collected when two axis tracking is done. However two axis tracking is relatively costly and complex. A compromise between maximum power collection and system simplicity is obtained by single axis tracking where the plane North south axis is fixed while the east west motion is accomplished. This work deals with the design of both single and two axis tracking systems. Automatic trackers is also compared to Fixed one in terms of Energy generated Efficiency Cost and System reliability.

  4. Ultrasound-guided internal jugular vein access: Comparison between short axis and long axis techniques

    Directory of Open Access Journals (Sweden)

    Tarek F Tammam

    2013-01-01

    Full Text Available The use of real-time ultrasound (US is advantageous in the insertion of central venous catheters (CVCs in adults, especially in whom difficulties are anticipated for various reasons. The aim of the present study was to compare two different real-time 2-dimensional US-guided techniques [short axis view/out-of-plane approach (SAX OOP approach versus long axis view/in-plane approach (LAX IP approach] for internal jugular vein (IJV cannulation. In this prospective study, 90 critical care and hemodialysis patients were assigned for insertion of CVCs using either the real-time US-guided (SAX OOP approach or LAX IP approach or landmark technique (control group. Failed catheter placement, risk of complications from placement, failure on first attempt at placement, number of attempts until successful catheterization, time to successful catheterization, incidence of central line-associated blood stream infection (CLA-BSI and demographics of each patient were recorded. There were no significant differences in patient′s demographic characteristics, side of cannulation (right or left or presence of risk factors for difficult venous cannulation between the three groups of patients. Cannulation of the IJV was achieved in all patients by using US (SAX OOP and LAX IP approaches and in 27 of the patients (90% by using the landmark technique (P = 0.045. Average access time (skin to vein and number of attempts were comparable between the SAX OOP and the LAX IP approaches while significantly reduced in both US groups of patients compared with the landmark group (P <0.001. In the landmark group, puncture of the carotid artery occurred in 16.7% of the patients, hematoma in 23.3% of the patients, pneumothorax in 3.3% of the patients and CLA-BSI in 20% of the patients, which were all significantly increased compared with the US group (P <0.05. The findings of this study suggest that the SAX OOP and LAX IP approaches were comparable for cannulation of IJV in critical

  5. Spatially incoherent common-path off-axis color digital holography.

    Science.gov (United States)

    Nguyen, Cuong M; Muhammad, Dilband; Kwon, Hyuk-Sang

    2018-02-20

    We describe a new method for recording spatially incoherent common-path off-axis color digital holograms. We present the theoretical and experimental evidence to demonstrate an incoherent common-path off-axis color digital holographic (ICOCH) system capable of capturing information from three-dimensional color objects under incoherent illumination, both in transmission and reflection modes. Fresnel incoherent correlation holography (FINCH), a common-path system, is a frequently used incoherent holography technique. Our proposed system is conceptually similar to an advanced form of FINCH; moreover, it has three advantages over this advanced form of FINCH. First, removal of the spatial light modulator makes our system simpler and more cost-effective. Second, removal of the polarizer or analyzer allows for greater light throughput. Third, the off-axis optical configuration enables separation of zero-order and twin images with only a single exposure per color rather than requiring three exposures per color for in-line holography FINCH. Therefore, we believe that this simple and cost-effective system with high light throughput can acquire incoherent holograms for different colors involving single exposure for each color, which makes the ICOCH system suitable for many applications.

  6. The Brain-Gut Axis Contributes to Neuroprogression in Stress-Related Disorders.

    Science.gov (United States)

    Rea, Kieran; Dinan, Timothy G; Cryan, John F

    2017-01-01

    There is a growing emphasis on the relationship between the complexity and diversity of the microorganisms that inhabit our gut (human gastrointestinal microbiota) and brain health. The microbiota-gut-brain axis is a dynamic matrix of tissues and organs including the brain, glands, gut, immune cells, and gastrointestinal microbiota that communicate in a complex multidirectional manner to maintain homeostasis. Changes in this environment may contribute to the neuroprogression of stress-related disorders by altering physiological processes including hypothalamic-pituitary-adrenal axis activation, neurotransmitter systems, immune function, and inflammatory responses. While appropriate, coordinated physiological responses, such as immune or stress responses, are necessary for survival, the contribution of repeated or chronic exposure to stress may predispose individuals to a more vulnerable state leaving them more susceptible to stress-related disorders. In this chapter, the involvement of the gastrointestinal microbiota in stress- and immune-mediated modulation of neuroendocrine, immune, and neurotransmitter systems and the consequential behavior is considered. We also focus on the mechanisms by which commensal gut microbiota can regulate neuroinflammation and further aim to exploit our understanding of their role in the effects of the microbiota-gut-brain axis on the neuroprogression of stress-related disorders as a consequence of neuroinflammatory processes. © 2017 S. Karger AG, Basel.

  7. Postnatal development of the atlas and axis: CT study

    International Nuclear Information System (INIS)

    Byun, Sung Su; Kim, Hyung Jin; Lim, Myung Kwan; Kim, Won Hong; Jeon, Yong Sun; Kim, Jeong Ho; Kim, Sung Tae

    2003-01-01

    To evaluate normal postnatal development of the atlas and axis by means of CT scanning. We prospectively analyzed CT scans of the developing atlas and axis of 200 normal children aged less than 14, investigating the CT appearance of these regions with particular attenuation to two synchondroses related to the atlas and four synchondroses and one ossification center related to the axis. Fusion varying was categorized as either low (grade1-5) or high (grade4-5), according to the varying degrees of fusion at each synchondrosis of ossification center. Neurocentral synchondrosis of the atlas was low grade in all children less than five, and high grade in all aged nine or more, while posterior synchondrosis of the atlas was low grade in 97% of children less than three and high grade in 99% aged three or more. As for the axis, neurocentral synchondrosis was low grade in all children less than three, and high grade in 97% of children aged five or more. PS of the axis was low grade in both children less than 6 months, and high grade in all aged two years or more. Dentocentral synchondrosis of the axis was low grade in 93% of children less than three and high grade in 96% of those aged at least five. Intradental axial synchondrosis was high grade in all children. Fusion of the terminal ossicle with the remainder of the dens was low in all children less than five and high in 97% of those aged nine of more. CT can help determine the parameters of normal postnatal development of the atlas and axis. A knowledge of normal ossification patterns of these regions may help provide an understanding of developmental anomalies and also help prevent confusion with fractures

  8. Novel aspects of hypothalamic-pituitary-adrenal axis regulation and glucocorticoid actions

    Science.gov (United States)

    Uchoa, Ernane Torres; Aguilera, Greti; Herman, James P.; Fiedler, Jenny L.; Deak, Terrence; Cordeiro de Sousa, Maria Bernardete

    2014-01-01

    Normal hypothalamic-pituitary-adrenal (HPA) axis activity leading to rhythmic and episodic release of adrenal glucocorticoids is essential for body homeostasis and survival during stress. Acting through specific intracellular receptors in the brain and periphery, glucocorticoids regulate behavior, metabolic, cardiovascular, immune, and neuroendocrine activities. In contrast to chronic elevated levels, circadian and acute stress-induced increases in glucocorticoids are necessary for hippocampal neuronal survival and memory acquisition and consolidation, through inhibiting apoptosis, facilitating glutamate transmission and inducing immediate early genes and spine formation. In addition to its metabolic actions leading to increasing energy availability, glucocorticoids have profound effects on feeding behavior, mainly through modulation of orexigenic and anorixegenic neuropeptides. Evidence is also emerging that in addition to the recognized immune suppressive actions of glucocorticoids by counteracting adrenergic proinflammatory actions, circadian elevations have priming effects in the immune system, potentiating acute defensive responses. In addition, negative feedback by glucocorticoids involves multiple mechanisms leading to limiting HPA axis activation and preventing deleterious effects of excessive glucocorticoid production. Adequate glucocorticoid secretion to meet body demands is tightly regulated by a complex neural circuitry controlling hypothalamic corticotrophin releasing hormone (CRH) and vasopressin secretion, the main regulators of pituitary adrenocorticotrophic hormone (ACTH). Rapid feedback mechanisms, likely involving non-genomic actions of glucocorticoids, mediate immediate inhibition of hypothalamic CRH and ACTH secretion, while intermediate and delayed mechanisms mediated by genomic actions involve modulation of limbic circuitry and peripheral metabolic messengers. Consistent with their key adaptive roles, HPA axis components are evolutionarily

  9. Mechanical impedance of the sitting human body in single-axis compared to multi-axis whole-body vibration exposure.

    Science.gov (United States)

    Holmlund, P; Lundström, R

    2001-01-01

    The study was aimed to investigate the mechanical impedance of the sitting human body and to compare data obtained in laboratory single-axis investigations with multi-axis data from in vehicle measurements. The experiments were performed in a laboratory for single-axis measurements. The multi-axis exposure was generated with an eight-seat minibus where the rear seats had been replaced with a rigid one. The subjects in the multi-axis experiment all participated in the single-axis experiments. There are quite a few investigations in the literature describing the human response to single-axis exposure. The response from the human body can be expected to be affected by multi-axis input in a different way than from a single-axis exposure. The present knowledge of the effect of multiple axis exposure is very limited. The measurements were performed using a specially designed force and accelerometer plate. This plate was placed between the subject and the hard seat. Outcome shows a clear difference between mechanical impedance for multi-axis exposure compared to single-axis. This is especially clear in the x-direction where the difference is very large. The conclusion is that it seems unlikely that single-axis mechanical impedance data can be directly transferred to a multi-axis environment. This is due to the force cross-talk between different directions.

  10. Vortex Breakdown Generated by off-axis Bifurcation in a cylinder with rotating covers

    DEFF Research Database (Denmark)

    Bisgaard, Anders; Brøns, Morten; Sørensen, Jens Nørkær

    2006-01-01

    Vortex breakdown of bubble type is studied for the flow in a cylinder with rotating top and bottom covers. For large ratios of the angular velocities of the covers, we observe numerically that the vortex breakdown bubble in the steady regime may occur through the creation of an off-axis vortex ring....... This scenario does not occur in existing bifurcation theory based on a simple degeneracy in the flow field. We extend the theory to cover a non-simple degeneracy, and derive the associated bifurcation diagrams. We show that the vortex breakdown scenario involving a vortex ring can be explained from this theory...

  11. Gut-brain axis: Role of lipids in the regulation of inflammation, pain and CNS diseases.

    Science.gov (United States)

    Russo, Roberto; Cristiano, Claudia; Avagliano, Carmen; De Caro, Carmen; La Rana, Giovanna; Raso, Giuseppina Mattace; Canani, Roberto Berni; Meli, Rosaria; Calignano, Antonio

    2017-02-16

    The human gut is a composite anaerobic environment with a large, diverse and dynamic enteric microbiota, represented by more than 100 trillion microorganisms, including at least 1000 distinct species. The discovery that a different microbial composition can influence behavior and cognition, and in turn the nervous system can indirectly influence enteric microbiota composition, has significantly contributed to establish the well-accepted concept of gut-brain axis. This hypothesis is supported by several evidence showing mutual mechanisms, which involve the vague nerve, the immune system, the hypothalamic-pituitary-adrenal (HPA) axis modulation and the bacteria-derived metabolites. Many studies have focused on delineating a role for this axis in health and disease, ranging from stress-related disorders such as depression, anxiety and irritable bowel syndrome (IBS) to neurodevelopmental disorders, such as autism, and to neurodegenerative diseases, such as Parkinson Disease, Alzheimer Disease etc. Based on this background, and considering the relevance of alteration of the symbiotic state between host and microbiota, this review focuses on the role and the involvement of bioactive lipids, such as the N-acylethanolamine (NAE) family whose main members are N-arachidonoylethanolamine (AEA), palmitoylethanolamide (PEA) and oleoilethanolamide (OEA), and short chain fatty acids (SCFAs), such as butyrate, belonging to a large group of bioactive lipids able to modulate peripheral and central pathologic processes. It is well established their effective role in inflammation, acute and chronic pain, obesity and central nervous system diseases. It has been shown a possible correlation between these lipids and gut microbiota through different mechanisms. Indeed, systemic administration of specific bacteria can reduce abdominal pain through the involvement of cannabinoid receptor 1 in rat; on the other hand, PEA reduces inflammation markers in a murine model of inflammatory bowel

  12. Who and What Does Involvement Involve?

    DEFF Research Database (Denmark)

    Hansen, Jeppe Oute; Petersen, A.; Huniche, L.

    2015-01-01

    , and on what grounds, involvement of relatives is perceived in Danish psychiatry. Paradoxically, the current understanding of involvement of relatives fails to take into consideration the perspectives of the relatives per se and families that were being studied. By analyzing involvement from a discourse...... the responsibility toward the mental health of the ill individual as well as toward the psychological milieu of the family....

  13. Measurement Axis Searching Model for Terrestrial Laser Scans Registration

    Directory of Open Access Journals (Sweden)

    Shaoxing Hu

    2016-01-01

    Full Text Available Nowadays, terrestrial Lidar scans can cover rather a large area; the point densities are strongly varied because of the line-of-sight measurement principle in potential overlaps with scans taken from different viewpoints. Most of the traditional methods focus on registration algorithm and ignore searching model. Sometimes the traditional methods are directly used to align two point clouds; a large critically unsolved problem of the large biases will be created in areas distant from the overlaps while the local overlaps are often aligned well. So a novel measurement axis searching model (MASM has been proposed in this paper. The method includes four steps: (1 the principal axis fitting, (2 the measurement axis generation, (3 low-high-precision search, and (4 result generation. The principal axis gives an orientation to the point cloud; the search scope is limited by the measurement axis. The point cloud orientation can be adjusted gradually until the achievement of the global optimum using low- and high-precision search. We perform some experiments with simulated point clouds and real terrestrial laser scans. The results of simulated point clouds have shown the processing steps of our method, and the results of real terrestrial laser scans have shown the sensitivity of the approach with respect to the indoor and outdoor scenes.

  14. Multi-Axis Heterodyne Interferometry (MAHI)

    Science.gov (United States)

    Thorpe, James

    The detection and measurement of gravitational waves represents humanity’s next, and final, opportunity to open an entirely new spectrum with which to view the universe. The first steps of this process will likely take place later this decade when the second-generation ground-based instruments such as Advanced LIGO approach design sensitivity. While these events will be historic, it will take a space-based detector to access the milliHertz gravitational wave frequency band, a band that is rich in both number and variety of sources. The Laser Interferometer Space Antenna (LISA) concept has been developed over the past two decades in the US and Europe to provide access to this band. The European Space Agency recently selected The Gravitational Universe as the science theme for the 3rd Large-class mission in the Cosmic Visions Programme, with the assumption that a LISA-like instrument would be implemented for launch in 2034. NASA has expressed interest in partnering on this effort and the US community has made its own judgment on the scientific potential of a space-based gravitational wave observatory through the selection of LISA as the 3rd flagship mission in the 2010 Decadal Survey. Much of the effort has been in retiring risk for the unique technologies that comprise a gravitational wave detector. A prime focus of this effort is LISA Pathfinder (LPF), a dedicated technology demonstrator mission led by ESA with contributions from NASA and several member states. LPF’s primary objective is to validate drag-free flight as an approach to realizing an inertial reference mass. Along the way, several important technologies will be demonstrated, including picometer-level heterodyne interferometry. However, there are several important differences between the interferometry design for LISA and that for LPF. These mostly result from the fact that LISA interferometry involves multiple lasers on separate spacecraft whereas LPF can use a single laser on a single spacecraft

  15. Dual axis operation of a micromachined rate gyroscope

    Energy Technology Data Exchange (ETDEWEB)

    Juneau, T. [BSAC, Berkeley, CA (United States); Pisano, A.P. [Univ. California, Berkeley, CA (United States). Dept. of Mechanical Engineering; Smith, J. [Sandia National Lab., Albuquerque, NM (United States)

    1997-04-01

    Since micromachining technology has raised the prospect of fabricating high performance sensors without the associated high cost and large size, many researchers have investigated micromachined rate gyroscopes. The vast majority of research has focused on single input axis rate gyroscopes, but this paper presents work on a dual input axis micromachined rate gyroscope. The key to successful simultaneous dual axis operation is the quad symmetry of the circular oscillating rotor design. Untuned gyroscopes with mismatched modes yielded random walk as low as 10{degrees}/{radical}hour with cross sensitivity ranging from 6% to 16%. Mode frequency matching via electrostatic tuning allowed performance better than 2{degrees}/{radical}hour, but at the expense of excessive cross sensitivity.

  16. Spin axis offset calibration on THEMIS using mirror modes

    Directory of Open Access Journals (Sweden)

    D. Frühauff

    2017-01-01

    Full Text Available A newly developed method for determining spin axis offsets of magnetic field instruments on spacecraft is applied to THEMIS. The formerly used determination method, relying on solar wind Alfvénic fluctuations, was rarely applicable due to the orbital restrictions of the mission. With the new procedure, based on magnetic field observation of mirror modes in the magnetosheath, updated spin axis offsets can be estimated approximately once per year. Retrospective calibration of all THEMIS magnetic field measurements is thereby made possible. Since, up to this point, spin axis offsets could hardly ever be calculated due to the mission's orbits, this update represents a substantial improvement to the data. The approximate offset stability is estimated to be < 0.75 nT year−1 for the complete course of the mission.

  17. Subquadratic medial-axis approximation in $\\mathbb{R}^3$

    Directory of Open Access Journals (Sweden)

    Christian Scheffer

    2015-09-01

    Full Text Available We present an algorithm that approximates the medial axis of a smooth manifold in $\\mathbb{R}^3$ which is given by a sufficiently dense point sample. The resulting, non-discrete approximation is shown to converge to the medial axis as the sampling density approaches infinity. While all previous algorithms guaranteeing convergence have a running time quadratic in the size $n$ of the point sample, we achieve a running time of at most $\\mathcal{O}(n\\log^3 n$. While there is no subquadratic upper bound on the output complexity of previous algorithms for non-discrete medial axis approximation, the output of our algorithm is guaranteed to be of linear size.

  18. Method of making a modular off-axis solar concentrator

    Science.gov (United States)

    Plesniak, Adam P.; Hall, John C.

    2017-05-23

    A method of making a solar concentrator may include forming a receiving wall having an elongated wall, a first side wall and a second side wall; attaching the first side wall and the second side wall to a reflecting wall to form a housing having an internal volume with an opening; forming a lip on the receiving wall and the reflecting wall; attaching a cover to the receiving wall and the reflecting wall at the lip to seal the opening into the internal volume, thereby creating a rigid structure; and mounting at least one receiver having at least one photovoltaic cell on the elongated wall to receive solar radiation entering the housing and reflected by the receiving wall, the receiver having an axis parallel with a surface normal of the photovoltaic cell, such that the axis is disposed at a non-zero angle relative to the vertical axis of the opening.

  19. The microbiota-gut-brain axis in functional gastrointestinal disorders.

    Science.gov (United States)

    De Palma, Giada; Collins, Stephen M; Bercik, Premysl

    2014-01-01

    Functional gastrointestinal disorders (FGIDs) are highly prevalent and pose a significant burden on health care and society, and impact patients' quality of life. FGIDs comprise a heterogeneous group of disorders, with unclear underlying pathophysiology. They are considered to result from the interaction of altered gut physiology and psychological factors via the gut-brain axis, where brain and gut symptoms are reciprocally influencing each other's expression. Intestinal microbiota, as a part of the gut-brain axis, plays a central role in FGIDs. Patients with Irritable Bowel Syndrome, a prototype of FGIDs, display altered composition of the gut microbiota compared with healthy controls and benefit, at the gastrointestinal and psychological levels, from the use of probiotics and antibiotics. This review aims to recapitulate the available literature on FGIDs and microbiota-gut-brain axis.

  20. Steroids, stress and the gut microbiome-brain axis.

    Science.gov (United States)

    Tetel, M J; de Vries, G J; Melcangi, R C; Panzica, G; O'Mahony, S M

    2018-02-01

    It is becoming well established that the gut microbiome has a profound impact on human health and disease. In this review, we explore how steroids can influence the gut microbiota and, in turn, how the gut microbiota can influence hormone levels. Within the context of the gut microbiome-brain axis, we discuss how perturbations in the gut microbiota can alter the stress axis and behaviour. In addition, human studies on the possible role of gut microbiota in depression and anxiety are examined. Finally, we present some of the challenges and important questions that need to be addressed by future research in this exciting new area at the intersection of steroids, stress, gut-brain axis and human health. © 2017 British Society for Neuroendocrinology.

  1. Off-axis and inline electron holography: Experimental comparison

    International Nuclear Information System (INIS)

    Latychevskaia, Tatiana; Formanek, Petr; Koch, C.T.; Lubk, Axel

    2010-01-01

    Electron holography is a very powerful technique for mapping static electric and magnetic potentials down to atomic resolution. While electron holography is commonly considered synonymous with its off-axis variant in the high energy electron microscopy community, inline electron holography is widely applied in low-energy electron microscopy, where the realization of the off-axis setup is still an experimental challenge. This paper demonstrates that both inline and off-axis holography may be used to recover amplitude and phase shift of the very same object, in our example latex spheres of 90 and 200 nm in diameter, producing very similar results, provided the object does not charge under the electron beam.

  2. The structure of genetic and environmental risk factors for syndromal and subsyndromal common DSM-IV axis I and all axis II disorders.

    Science.gov (United States)

    Kendler, Kenneth S; Aggen, Steven H; Knudsen, Gun Peggy; Røysamb, Espen; Neale, Michael C; Reichborn-Kjennerud, Ted

    2011-01-01

    The authors sought to clarify the structure of the genetic and environmental risk factors for 22 DSM-IV disorders: 12 common axis I disorders and all 10 axis II disorders. The authors examined syndromal and subsyndromal axis I diagnoses and five categories reflecting number of endorsed criteria for axis II disorders in 2,111 personally interviewed young adult members of the Norwegian Institute of Public Health Twin Panel. Four correlated genetic factors were identified: axis I internalizing, axis II internalizing, axis I externalizing, and axis II externalizing. Factors 1 and 2 and factors 3 and 4 were moderately correlated, supporting the importance of the internalizing-externalizing distinction. Five disorders had substantial loadings on two factors: borderline personality disorder (factors 3 and 4), somatoform disorder (factors 1 and 2), paranoid and dependent personality disorders (factors 2 and 4), and eating disorders (factors 1 and 4). Three correlated environmental factors were identified: axis II disorders, axis I internalizing disorders, and externalizing disorders versus anxiety disorders. Common axis I and II psychiatric disorders have a coherent underlying genetic structure that reflects two major dimensions: internalizing versus externalizing, and axis I versus axis II. The underlying structure of environmental influences is quite different. The organization of common psychiatric disorders into coherent groups results largely from genetic, not environmental, factors. These results should be interpreted in the context of unavoidable limitations of current statistical methods applied to this number of diagnostic categories.

  3. Calibration of three-axis magnetometers with differential evolution algorithm

    Energy Technology Data Exchange (ETDEWEB)

    Pang, Hongfeng, E-mail: panghongfeng@126.com [College of Mechatronics Engineering and Automation, National University of Defense Technology, Changsha 410073 (China); Zhang, Qi [College of Mechatronics Engineering and Automation, National University of Defense Technology, Changsha 410073 (China); Wang, Wei [Northwest Institute of Nuclear Technology, Xian 710024 (China); Wang, Junya; Li, Ji; Luo, Shitu; Wan, Chengbiao; Chen, Dixiang; Pan, Mengchun; Luo, Feilu [College of Mechatronics Engineering and Automation, National University of Defense Technology, Changsha 410073 (China)

    2013-11-15

    The accuracy of three-axis magnetometers is influenced by different scale and bias of each axis and nonorthogonality between axes. One limitation of traditional iteration methods is that initial parameters influence the calibration, thus leading to the local optimal or wrong results. In this paper, a new method is proposed to calibrate three-axis magnetometers. To employ this method, a nonmagnetic rotation platform, a proton magnetometer, a DM-050 three-axis magnetometer and the differential evolution (DE) algorithm are used. The performance of this calibration method is analyzed with simulation and experiment. In simulation, the calibration results of DE, unscented Kalman filter (UKF), recursive least squares (RLS) and genetic algorithm (GA) are compared. RMS error using DE is least, which is reduced from 81.233 nT to 1.567 nT. Experimental results show that comparing with UKF, RLS and GA, the DE algorithm has not only the least calibration error but also the best robustness. After calibration, RMS error is reduced from 68.914 nT to 2.919 nT. In addition, the DE algorithm is not sensitive to initial parameters, which is an important advantage compared with traditional iteration algorithms. The proposed algorithm can avoid the troublesome procedure to select suitable initial parameters, thus it can improve the calibration performance of three-axis magnetometers. - Highlights: • The calibration results and robustness of UKF, GA, RLS and DE algorithm are analyzed. • Calibration error of DE is the least in simulation and experiment. • Comparing with traditional calibration algorithms, DE is not sensitive to initial parameters. • It can improve the calibration performance of three-axis magnetometers.

  4. Calibration of three-axis magnetometers with differential evolution algorithm

    International Nuclear Information System (INIS)

    Pang, Hongfeng; Zhang, Qi; Wang, Wei; Wang, Junya; Li, Ji; Luo, Shitu; Wan, Chengbiao; Chen, Dixiang; Pan, Mengchun; Luo, Feilu

    2013-01-01

    The accuracy of three-axis magnetometers is influenced by different scale and bias of each axis and nonorthogonality between axes. One limitation of traditional iteration methods is that initial parameters influence the calibration, thus leading to the local optimal or wrong results. In this paper, a new method is proposed to calibrate three-axis magnetometers. To employ this method, a nonmagnetic rotation platform, a proton magnetometer, a DM-050 three-axis magnetometer and the differential evolution (DE) algorithm are used. The performance of this calibration method is analyzed with simulation and experiment. In simulation, the calibration results of DE, unscented Kalman filter (UKF), recursive least squares (RLS) and genetic algorithm (GA) are compared. RMS error using DE is least, which is reduced from 81.233 nT to 1.567 nT. Experimental results show that comparing with UKF, RLS and GA, the DE algorithm has not only the least calibration error but also the best robustness. After calibration, RMS error is reduced from 68.914 nT to 2.919 nT. In addition, the DE algorithm is not sensitive to initial parameters, which is an important advantage compared with traditional iteration algorithms. The proposed algorithm can avoid the troublesome procedure to select suitable initial parameters, thus it can improve the calibration performance of three-axis magnetometers. - Highlights: • The calibration results and robustness of UKF, GA, RLS and DE algorithm are analyzed. • Calibration error of DE is the least in simulation and experiment. • Comparing with traditional calibration algorithms, DE is not sensitive to initial parameters. • It can improve the calibration performance of three-axis magnetometers

  5. ATX-LPA receptor axis in inflammation and cancer.

    Science.gov (United States)

    Liu, Shuying; Murph, Mandi; Panupinthu, Nattapon; Mills, Gordon B

    2009-11-15

    Lysophosphatidic acid (LPA, 1- or 2-acyl-sn-glycerol 3-phosphate) mediates a plethora of physiological and pathological activities via interactions with a series of high affinity G protein-coupled receptors (GPCR). Both LPA receptor family members and autotaxin (ATX/LysoPLD), the primary LPA-producing enzyme, are aberrantly expressed in many human breast cancers and several other cancer lineages. Using transgenic mice expressing either an LPA receptor or ATX, we recently demonstrated that the ATX-LPA receptor axis plays a causal role in breast tumorigenesis and cancer-related inflammation, further validating the ATX-LPA receptor axis as a rich therapeutic target in cancer.

  6. Nearly-off-axis transmissivity of Solc birefringent filters.

    Science.gov (United States)

    Zhou, Yu; Liu, Liren; Zhang, Juan; Liu, De'an; Luan, Zhu

    2003-04-01

    The characteristics of light propagating near the axis of a birefringent filter are studied. A generalized formulation to describe the nearly-off-axis transmissivity of a Solc birefringent filter is derived. On this basis, the polarization conoscopic figures of Solc filters with different numbers of birefringent plates are simulated. Furthermore the variation of spectral transmission with angle of incidence is analyzed, and the field-of-view transmissivity and the spectral transmissivity averaged with respect to the spread of incident light are given. Primary experiments for verification are also demonstrated.

  7. The properties of on-axis coupled structure RF gun

    CERN Document Server

    Oda, F; Nakayama, A; Koike, H; Tanabe, E

    2000-01-01

    Kawasaki Heavy Industries Ltd. (KHI) has developed the compact IR FEL device, which adopts a combination of a newly designed RF gun with a thermionic cathode and an alpha-magnet as an injector. The accelerating mode of the S-band RF gun is a pi/2 standing wave mode. The coupling cell is located on the beam axis, the so-called on-axis coupled structure (OCS). The cavity shape was designed by using electromagnetic field analytical codes. The OCS RF gun was manufactured and the electromagnetic properties were measured. The results show good agreement with the simulations.

  8. Research on Parameter Design of Multi - axis Hydrostatic Transmission Vehicle

    Directory of Open Access Journals (Sweden)

    Zhao Liang

    2017-01-01

    Full Text Available In order to obtain reasonable parameters in the design of driving system of multi-axis hydrostatic transmission vehicle, the working principle of single-side drive of hydrostatic transmission vehicle is introduced. The matching and control of engine and hydraulic pump are analyzed. According to the driving equation of vehicle, The driving force required for driving system is determined, and the parameters of hydraulic motor, hydraulic pump, system working pressure and braking system are designed and calculated, which provides the parameter design for driving system of multi-axis hydrostatic transmission Reliable theoretical basis.

  9. Targeting the gut-liver axis in cirrhosis

    DEFF Research Database (Denmark)

    Madsen, Bjørn S; Havelund, Troels; Krag, Aleksander

    2013-01-01

    The gut-liver axis in cirrhosis and portal hypertension is gaining increasing attention as a key pathophysiological mechanism responsible for progression of liver failure and development of complications such as spontaneous infections and hepatocellular carcinoma. Antibiotics and non-selective β......-blockers (NSBB) intercept this axis and each drug has proven efficacy in clinical trials. A synergistic effect is a hitherto unproven possibility. There is an increasing body of evidence supporting improved outcome with expanded use of NSBB and antibiotic therapy beyond current indications. This review addresses...

  10. Three axis vector atomic magnetometer utilizing polarimetric technique

    Energy Technology Data Exchange (ETDEWEB)

    Pradhan, Swarupananda, E-mail: spradhan@barc.gov.in, E-mail: pradhans75@gmail.com [Laser and Plasma Technology Division, Bhabha Atomic Research Centre, Mumbai 400085, India and Homi Bhabha National Institute, Department of Atomic Energy, Mumbai 400094 (India)

    2016-09-15

    The three axis vector magnetic field measurement based on the interaction of a single elliptically polarized light beam with an atomic system is described. The magnetic field direction dependent atomic responses are extracted by the polarimetric detection in combination with laser frequency modulation and magnetic field modulation techniques. The magnetometer geometry offers additional critical requirements like compact size and large dynamic range for space application. Further, the three axis magnetic field is measured using only the reflected signal (one polarization component) from the polarimeter and thus can be easily expanded to make spatial array of detectors and/or high sensitivity field gradient measurement as required for biomedical application.

  11. Microbiota-gut-brain axis and the central nervous system.

    Science.gov (United States)

    Zhu, Xiqun; Han, Yong; Du, Jing; Liu, Renzhong; Jin, Ketao; Yi, Wei

    2017-08-08

    The gut and brain form the gut-brain axis through bidirectional nervous, endocrine, and immune communications. Changes in one of the organs will affect the other organs. Disorders in the composition and quantity of gut microorganisms can affect both the enteric nervous system and the central nervous system (CNS), thereby indicating the existence of a microbiota-gut-brain axis. Due to the intricate interactions between the gut and the brain, gut symbiotic microorganisms are closely associated with various CNS diseases, such as Parkinson's disease, Alzheimer's disease, schizophrenia, and multiple sclerosis. In this paper, we will review the latest advances of studies on the correlation between gut microorganisms and CNS functions & diseases.

  12. The Microbiome-Gut-Brain Axis in Health and Disease.

    Science.gov (United States)

    Dinan, Timothy G; Cryan, John F

    2017-03-01

    Gut microbes are capable of producing most neurotransmitters found in the human brain. Evidence is accumulating to support the view that gut microbes influence central neurochemistry and behavior. Irritable bowel syndrome is regarded as the prototypic disorder of the brain-gut-microbiota axis that can be responsive to probiotic therapy. Translational studies indicate that certain bacteria may have an impact on stress responses and cognitive functioning. Manipulating the gut microbiota with psychobiotics, prebiotics, or even antibiotics offers a novel approach to altering brain function and treating gut-brain axis disorders, such as depression and autism. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Diazepam increases the hypothalamic-pituitary-adrenocortical (HPA) axis activity by a cyclic AMP-dependent mechanism

    Science.gov (United States)

    Vargas, M Luisa; Abella, Cristina; Hernandez, Jesus

    2001-01-01

    Previous studies in this laboratory have shown that diazepam behaves as a phosphodiesterase 4 (PDE 4) inhibitor. It has been reported that PDE-4 inhibitors activate the hypothalamic-pituitary-adrenocortical (HPA) axis in the rat. In the present study we have examined whether activation of the cyclic AMP-dependent protein kinase (PKA) is involved in the effect of diazepam on basal HPA axis activity. Acute systemic administration of diazepam (10 mg kg−1 i.p.) was found to increase the basal HPA axis activity, increasing the plasma concentrations of corticotrophin (ACTH) and corticosterone 30 min post injection. Diazepam also elevated cyclic AMP content of the hypothalamus. Pretreatment of the animals with dexamethasone (1 mg kg−1 s.c.) for 3 days completely abolished the effect of diazepam on HPA axis activity. The antagonists of central and peripheral benzodiazepine receptors, flumazenil (10 mg kg−1 i.p.) and PK 11195 (5 mg kg−1 i.p.) did not affect the diazepam induced increase of HPA axis activity nor did they have an effect per se. The increase in ACTH and corticosterone levels was significantly reduced by the cyclic AMP-dependent protein kinase (PKA) inhibitor, H-89, given either subcutaneously (5 mg kg−1 s.c.) or intracerebroventricularly (i.c.v.; 28 μg in 10 μl). The results indicate that diazepam can stimulate basal HPA axis activity in the rat by a cyclic AMP-dependent PKA mediated pathway. PMID:11498522

  14. Multi-Axis Identifiability Using Single-Surface Parameter Estimation Maneuvers on the X-48B Blended Wing Body

    Science.gov (United States)

    Ratnayake, Nalin A.; Koshimoto, Ed T.; Taylor, Brian R.

    2011-01-01

    The problem of parameter estimation on hybrid-wing-body type aircraft is complicated by the fact that many design candidates for such aircraft involve a large number of aero- dynamic control effectors that act in coplanar motion. This fact adds to the complexity already present in the parameter estimation problem for any aircraft with a closed-loop control system. Decorrelation of system inputs must be performed in order to ascertain individual surface derivatives with any sort of mathematical confidence. Non-standard control surface configurations, such as clamshell surfaces and drag-rudder modes, further complicate the modeling task. In this paper, asymmetric, single-surface maneuvers are used to excite multiple axes of aircraft motion simultaneously. Time history reconstructions of the moment coefficients computed by the solved regression models are then compared to each other in order to assess relative model accuracy. The reduced flight-test time required for inner surface parameter estimation using multi-axis methods was found to come at the cost of slightly reduced accuracy and statistical confidence for linear regression methods. Since the multi-axis maneuvers captured parameter estimates similar to both longitudinal and lateral-directional maneuvers combined, the number of test points required for the inner, aileron-like surfaces could in theory have been reduced by 50%. While trends were similar, however, individual parameters as estimated by a multi-axis model were typically different by an average absolute difference of roughly 15-20%, with decreased statistical significance, than those estimated by a single-axis model. The multi-axis model exhibited an increase in overall fit error of roughly 1-5% for the linear regression estimates with respect to the single-axis model, when applied to flight data designed for each, respectively.

  15. The Vagus Nerve at the Interface of the Microbiota-Gut-Brain Axis.

    Science.gov (United States)

    Bonaz, Bruno; Bazin, Thomas; Pellissier, Sonia

    2018-01-01

    The microbiota, the gut, and the brain communicate through the microbiota-gut-brain axis in a bidirectional way that involves the autonomic nervous system. The vagus nerve (VN), the principal component of the parasympathetic nervous system, is a mixed nerve composed of 80% afferent and 20% efferent fibers. The VN, because of its role in interoceptive awareness, is able to sense the microbiota metabolites through its afferents, to transfer this gut information to the central nervous system where it is integrated in the central autonomic network, and then to generate an adapted or inappropriate response. A cholinergic anti-inflammatory pathway has been described through VN's fibers, which is able to dampen peripheral inflammation and to decrease intestinal permeability, thus very probably modulating microbiota composition. Stress inhibits the VN and has deleterious effects on the gastrointestinal tract and on the microbiota, and is involved in the pathophysiology of gastrointestinal disorders such as irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) which are both characterized by a dysbiosis. A low vagal tone has been described in IBD and IBS patients thus favoring peripheral inflammation. Targeting the VN, for example through VN stimulation which has anti-inflammatory properties, would be of interest to restore homeostasis in the microbiota-gut-brain axis.

  16. On the Turbulent Mixing in Horizontal Axis Wind Turbine Wakes

    NARCIS (Netherlands)

    Lignarolo, L.E.M.

    2016-01-01

    The wake flow of a horizontal axis wind turbine is characterised by lower wind speed and higher turbulence than the free-stream conditions. When clustered in large wind farms, wind turbines regularly operate inside the wake of one or more upstream machines. This is a major cause of energy production

  17. An improved computer controlled triple-axis neutron spectrometer

    International Nuclear Information System (INIS)

    Cooper, M.J.; Hall, J.W.; Hutchings, M.T.

    1975-07-01

    A description is given of the computer-controlled triple-axis neutron spectrometer installed at the PLUTO reactor at Harwell. The reasons for an nature of recent major improvements are discussed. Following a general description of the spectrometer, details are then given of the new computerised control system, including the functions of the various programs which are now available to the user. (author)

  18. Evidence of a liver-alpha cell axis in humans

    DEFF Research Database (Denmark)

    Wewer Albrechtsen, Nicolai J; Færch, Kristine; Jensen, Troels M

    2018-01-01

    in plasma γ-glutamyltransferase levels. CONCLUSIONS/INTERPRETATION: This cross-sectional study supports the existence of a liver-alpha cell axis in humans: glucagon regulates plasma levels of amino acids, which in turn feedback to regulate the secretion of glucagon. With hepatic insulin resistance...

  19. The GH/IGF-1 axis in ageing and longevity

    Science.gov (United States)

    List, Edward O.; Berryman, Darlene E.; Murrey, John W.

    2014-01-01

    Secretion of growth hormone (GH), and consequently that of insulin-like growth factor 1 (IGF-1), declines over time until only low levels can be detected in individuals aged ≥60 years. This phenomenon, which is known as the ‘somatopause’, has led to recombinant human GH being widely promoted and abused as an antiageing drug, despite lack of evidence of efficacy. By contrast, several mutations that decrease the tone of the GH/IGF-1 axis are associated with extended longevity in mice. In humans, corresponding or similar mutations have been identified, but whether these mutations alter longevity has yet to be established. The powerful effect of reduced GH activity on lifespan extension in mice has generated the hypothesis that pharmaceutically inhibiting, rather than increasing, GH action might delay ageing. Moreover, mice as well as humans with reduced activity of the GH/IGF-1 axis are protected from cancer and diabetes mellitus, two major ageing-related morbidities. Here, we review data on mouse strains with alterations in the GH/IGF-1 axis and their effects on lifespan. The outcome of corresponding or similar mutations in humans is described, as well as the potential mechanisms underlying increased longevity and the therapeutic benefits and risks of medical disruption of the GH/IGF-1 axis in humans. PMID:23591370

  20. Comparison of aerodynamic models for Vertical Axis Wind Turbines

    NARCIS (Netherlands)

    Simao Ferreira, C.J.; Aagaard Madsen, H.; Barone, M.; Roscher, B.; Deglaire, P.; Arduin, I.

    2014-01-01

    Multi-megawatt Vertical Axis Wind Turbines (VAWTs) are experiencing an increased interest for floating offshore applications. However, VAWT development is hindered by the lack of fast, accurate and validated simulation models. This work compares six different numerical models for VAWTS: a multiple

  1. On-axis conoscopic holography without a conjugate image.

    Science.gov (United States)

    Mugnier, L M; Sirat, G Y

    1992-02-15

    We present a method for removing the conjugate image in an incoherent-light holographic technique, namely, on-axis conoscopic holography. The point-spread function that we obtain is that of a complex Gabor zone pattern, which thus should allow good-quality reconstructions of objects. Experimental results are also presented, which confirm the validity of this method.

  2. QRS Axis deviation in Nigeria women during normal pregnancy ...

    African Journals Online (AJOL)

    The effect of pregnancy on the heart rate, respiratory rate, QRS axis and QRS complex duration of the ECG was investigated din 41 pregnant compared to 39 non pregnant age and height matched Nigeria subjects. Results obtained show that pregnancy had no significant effect (p>0.05) on heart rate, respiratory rate and ...

  3. The enteroinsular axis in dipeptidyl peptidase IV-negative rats

    DEFF Research Database (Denmark)

    Pederson, Raymond; Kieffer, T J; Pauly, R

    1996-01-01

    were used in the current investigation as a model for examining the enteroinsular axis under conditions in which normal inactivation of GIP and GLP-1(7-36) does not occur. This was assessed by comparing GIP and GLP-1(7-36) responses following oral glucose in normal versus DPIV-deficient Fischer rats...

  4. The apolipoprotein m-sphingosine-1-phosphate axis

    DEFF Research Database (Denmark)

    Arkensteijn, Bas W C; Berbée, Jimmy F P; Rensen, Patrick C N

    2013-01-01

    -receptor-1, affecting the function of endothelial cells, and apoM-deficient mice display impaired endothelial permeability in the lung. This review will focus on the putative biological roles of the new apoM-S1P axis in relation to lipoprotein metabolism, lipid disorders and atherosclerosis....

  5. Genetic loci mapping for ear axis weight using recombinant inbred ...

    African Journals Online (AJOL)

    Ear axis weight (EAW) is one of the important agronomic traits in maize (Zea mays L.), related to yield. To understand its genetic basis, a recombinant inbred line (RIL) population, derived from the cross Mo17 × Huangzao4, was used for quantitative trait locus mapping (QTL) for EAW under high and low nitrogen (N) regimes.

  6. Analysis of horizontal axis wind turbine blade using CFD | Nigam ...

    African Journals Online (AJOL)

    Blade is very essential part of HAWT (horizontal axis wind turbine). Forces for Lift and drag on the blade has an important role in the wind turbine performance. The main purpose of this work is to perform CFD analysis of a blade and airfoil of wind turbine using k-ω SST model. In this present study NACA 634 -221 airfoil ...

  7. Comparison of aerodynamic models for Vertical Axis Wind Turbines

    DEFF Research Database (Denmark)

    Ferreira, C. Simão; Aagaard Madsen, Helge; Barone, M.

    2014-01-01

    Multi-megawatt Vertical Axis Wind Turbines (VAWTs) are experiencing an increased interest for floating offshore applications. However, VAWT development is hindered by the lack of fast, accurate and validated simulation models. This work compares six different numerical models for VAWTS: a multipl...

  8. Super earth explorer: a coronagraphic off-axis space telescope

    NARCIS (Netherlands)

    Stam, D.; Keller, C.U.

    2009-01-01

    The Super-Earth Explorer is an Off-Axis Space Telescope (SEE-COAST) designed for high contrast imaging. Its scientific objective is to make the physico-chemical characterization of exoplanets possibly down to 2 Earth radii. For that purpose it will analyze the spectral and polarimetric properties of

  9. Analysis of off-axis tension test of wood specimens

    Science.gov (United States)

    Jen Y. Liu

    2002-01-01

    This paper presents a stress analysis of the off-axis tension test of clear wood specimens based on orthotropic elasticity theory. The effects of Poisson's ratio and shear coupling coefficient on stress distribution are analyzed in detail. The analysis also provides a theoretical foundation for the selection of a 10° grain angle in wood specimens for the...

  10. Brain-gut-microbiota axis in Parkinson's disease.

    Science.gov (United States)

    Mulak, Agata; Bonaz, Bruno

    2015-10-07

    Parkinson's disease (PD) is characterized by alpha-synucleinopathy that affects all levels of the brain-gut axis including the central, autonomic, and enteric nervous systems. Recently, it has been recognized that the brain-gut axis interactions are significantly modulated by the gut microbiota via immunological, neuroendocrine, and direct neural mechanisms. Dysregulation of the brain-gut-microbiota axis in PD may be associated with gastrointestinal manifestations frequently preceding motor symptoms, as well as with the pathogenesis of PD itself, supporting the hypothesis that the pathological process is spread from the gut to the brain. Excessive stimulation of the innate immune system resulting from gut dysbiosis and/or small intestinal bacterial overgrowth and increased intestinal permeability may induce systemic inflammation, while activation of enteric neurons and enteric glial cells may contribute to the initiation of alpha-synuclein misfolding. Additionally, the adaptive immune system may be disturbed by bacterial proteins cross-reacting with human antigens. A better understanding of the brain-gut-microbiota axis interactions should bring a new insight in the pathophysiology of PD and permit an earlier diagnosis with a focus on peripheral biomarkers within the enteric nervous system. Novel therapeutic options aimed at modifying the gut microbiota composition and enhancing the intestinal epithelial barrier integrity in PD patients could influence the initial step of the following cascade of neurodegeneration in PD.

  11. Microbiota-Brain-Gut Axis and Neurodegenerative Diseases.

    Science.gov (United States)

    Quigley, Eamonn M M

    2017-10-17

    The purposes of this review were as follows: first, to provide an overview of the gut microbiota and its interactions with the gut and the central nervous system (the microbiota-gut-brain axis) in health, second, to review the relevance of this axis to the pathogenesis of neurodegenerative diseases, such as Parkinson's disease, and, finally, to assess the potential for microbiota-targeted therapies. Work on animal models has established the microbiota-gut-brain axis as a real phenomenon; to date, the evidence for its operation in man has been limited and has been confronted by considerable logistical challenges. Animal and translational models have incriminated a disturbed gut microbiota in a number of CNS disorders, including Parkinson's disease; data from human studies is scanty. While a theoretical basis can be developed for the use of microbiota-directed therapies in neurodegenerative disorders, support is yet to come from high-quality clinical trials. In theory, a role for the microbiota-gut-brain axis is highly plausible; clinical confirmation is awaited.

  12. Microbiota regulation of the Mammalian gut-brain axis.

    Science.gov (United States)

    Burokas, Aurelijus; Moloney, Rachel D; Dinan, Timothy G; Cryan, John F

    2015-01-01

    The realization that the microbiota-gut-brain axis plays a critical role in health and disease has emerged over the past decade. The brain-gut axis is a bidirectional communication system between the central nervous system (CNS) and the gastrointestinal tract. Regulation of the microbiota-brain-gut axis is essential for maintaining homeostasis, including that of the CNS. The routes of this communication are not fully elucidated but include neural, humoral, immune, and metabolic pathways. A number of approaches have been used to interrogate this axis including the use of germ-free animals, probiotic agents, antibiotics, or animals exposed to pathogenic bacterial infections. Together, it is clear that the gut microbiota can be a key regulator of mood, cognition, pain, and obesity. Understanding microbiota-brain interactions is an exciting area of research which may contribute new insights into individual variations in cognition, personality, mood, sleep, and eating behavior, and how they contribute to a range of neuropsychiatric diseases ranging from affective disorders to autism and schizophrenia. Finally, the concept of psychobiotics, bacterial-based interventions with mental health benefit, is also emerging. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. The Minimal Model of the Hypothalamic-Pituitary-Adrenal Axis

    DEFF Research Database (Denmark)

    Vinther, Frank; Andersen, Morten; Ottesen, Johnny T.

    2011-01-01

    from an unstable fixed point with complex eigenvalues with a positive real parts and a non-zero imaginary parts. The first part of the paper describes the general considerations to be obeyed for a mathematical model of the HPA axis. In this paper we only include the most widely accepted mechanisms...

  14. Phytochemicals for taming agitated immune-endocrine-neural axis.

    Science.gov (United States)

    Patel, Seema

    2017-07-01

    Homeostasis of immune-endocrine-neural axis is paramount for human health. If this axis gets agitated due to age, genetic variations, environmental exposures or lifestyle assaults, a cascade of adverse reactions occurs in human body. Cytokines, hormones and neurotransmitters, the effector molecules of this axis behave erratically, leading to a gamut of neural, endocrine, autoimmune, and metabolic diseases. Current panel of drugs can tackle some of them but not in a sustainable, benign way as a myriad of side effects, causal of them have been documented. In this context, phytochemicals, the secondary metabolites of plants seem beneficial. These bioactive constituents encompassing polyphenols, alkaloids, flavonoids, terpenoids, tannins, lignans, stilbenoids (resveratrol), saponins, polysaccharides, glycosides, and lectins etc. have been proven to exert antioxidant, anti-inflammatory, hypolipidemic, hypotensive, antidiabetic, anticancer, immunomodulatory, anti-allergic, analgesic, hepatoprotective, neuroprotective, dermatoprotective, and antimicrobial properties, among a litany of other biological effects. This review presents a holistic perspective of common afflictions resultant of immune-endocrine-neural axis disruption, and the phytochemicals capable of restoring their normalcy and mitigating the ailments. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  15. Local charge measurement using off-axis electron holography

    DEFF Research Database (Denmark)

    Beleggia, Marco; Gontard, L.C.; Dunin-Borkowski, R.0E.

    2016-01-01

    A model-independent approach based on Gauss’ theorem for measuring the local charge in a specimen from an electron-optical phase image recorded using off-axis electron holography was recently proposed. Here, we show that such a charge measurement is reliable when it is applied to determine...

  16. Surgical management of giant cell tumor of axis vertebra: review of fourteen cases in literature with a case illustration

    Directory of Open Access Journals (Sweden)

    Satyarthee Guru Dutta

    2017-09-01

    Full Text Available Primary spinal giant cell tumor (PSGCT considered as rare primary neoplasm, with predilection for subarticular location and commonly located at knee joint region, sacrum or distal radius, however, spinal involvent is uncommon and comparatively much rarer in the cervical spine. Further occurrence of giant cell tumor in the Axis vertebra is extremely uncommon and easily misdiagnosed and, thus, treatment is still debated and various treatment modalities and different surgical approaches were utilized during evolution of surgical management. Authors could collect only 14 cases of primary giant cell tumor affecting Axis vertebra in a detailed Pubmed and Medline search, out of which 12 cases were primary and rest two case was recurrent. So authors reviewed in total thirteen cases primary giant cell tumor of Axis managed surgically, including our case. Out of 13 PSGCT, twelve cases were managed with surgical resection and the rest one case was managed with monoclonal antibody using Denosomab monotherapy without any surgical intervention. In the surgical group (n=12, nine cases had two staged surgical procedure, first being posterior fixation followed by anterior approach with resection of tumor while, the rest three had one stage surgical resection including current case. Authors reports a unique case of spinal giant cell tumor developing in a- 38 - year male with history of renal transplant, presented with neck pain and difficulty in walking, neuroimaging revealed a osteolytic mass lesion involving body of axis vertebra with extension into right sided lamina, underwent two stage complete surgical intervention. Authors describes management of such rare locally recurring primary bony pathology affecting axis vertebra as it is not only interesting and challenging and different management modalities, various, surgical approaches and issue of renal osteodystrophy along with pertinent literature is also reviewed briefly.

  17. Eye Involvement in TSC

    Science.gov (United States)

    ... Privacy Policy Sitemap Learn Engage Donate About TSC Eyes Campbell (1905) first described the eye involvement in ... some form of eye involvement. Nonretinal and Retinal Eye Findings Facial angiofibromas may involve the eyelids of ...

  18. A Trio-Rac1-PAK1 signaling axis drives invadopodia disassembly

    Science.gov (United States)

    Moshfegh, Yasmin; Bravo-Cordero, Jose Javier; Miskolci, Veronika; Condeelis, John; Hodgson, Louis

    2014-01-01

    Rho family GTPases control cell migration and participate in the regulation of cancer metastasis. Invadopodia, associated with invasive tumor cells, are crucial for cellular invasion and metastasis. To study Rac1 GTPase in invadopodia dynamics, we developed a genetically-encoded, single-chain Rac1 Fluorescence Resonance Energy Transfer (FRET) biosensor. The biosensor shows Rac1 activity exclusion from the core of invadopodia, and higher activity when invadopodia disappear, suggesting that reduced Rac1 activity is necessary for their stability, and Rac1 activation is involved in disassembly. Photoactivating Rac1 at invadopodia confirmed this previously-unknown Rac1 function. We built an invadopodia disassembly model, where a signaling axis involving TrioGEF, Rac1, PAK1, and phosphorylation of cortactin, causing invadopodia dissolution. This mechanism is critical for the proper turnover of invasive structures during tumor cell invasion, where a balance of proteolytic activity and locomotory protrusions must be carefully coordinated to achieve a maximally invasive phenotype. PMID:24859002

  19. Serdemetan antagonizes the Mdm2-HIF1α axis leading to decreased levels of glycolytic enzymes.

    Directory of Open Access Journals (Sweden)

    Jason A Lehman

    Full Text Available Serdemetan (JNJ-26854165, an antagonist to Mdm2, was anticipated to promote the activation of p53. While regulation of p53 by Mdm2 is important, Mdm2 also regulates numerous proteins involved in diverse cellular functions. We investigated if Serdemetan would alter the Mdm2-HIF1α axis and affect cell survival in human glioblastoma cells independently of p53. Treatment of cells with Serdemetan under hypoxia resulted in a decrease in HIF1α levels. HIF1α downstream targets, VEGF and the glycolytic enzymes (enolase, phosphoglycerate kinase1/2, and glucose transporter 1, were all decreased in response to Serdemetan. The involvement of Mdm2 in regulating gene expression of glycolytic enzymes raises the possibility of side effects associated with therapeutically targeting Mdm2.

  20. GRB 170817A: a short GRB seen off-axis

    Science.gov (United States)

    He, Xin-Bo; Tam, Pak-Hin Thomas; Shen, Rong-Feng

    2018-04-01

    The angular distribution of gamma-ray burst (GRB) jets is not yet clear. The observed luminosity of GRB 170817A is the lowest among all known short GRBs, which is best explained by the fact that our line of sight is outside of the jet opening angle, θ obs > θ j , where θ obs is the angle between our line of sight and the jet axis. As inferred by gravitational wave observations, as well as radio and X-ray afterglow modeling of GRB 170817A, it is likely that θ obs ∼ 20° – 28°. In this work, we quantitatively consider two scenarios of angular energy distribution of GRB ejecta: a top-hat jet and a structured jet with a power law index s. For the top-hat jet model, we get a large θ j (e.g., θ j > 10°), a rather high local (i.e., z 7.5 × 104, keV (∼500, keV for a typical short GRB). For the structured jet model, we use θ obs to give limits on s and θj for typical on-axis luminosity of a short GRB (e.g., 1049 erg s‑1 ∼ 1051 erg s‑1), and a low on-axis luminosity case (e.g., 1049 erg s‑1) gives more reasonable values of s. The structured jet model is more feasible for GRB 170817A than the top-hat jet model due to the rather high local short GRB rate, and the extremely high on-axis E peak,0 almost rules out the top-hat jet model. GRB 170817A is likely a low on-axis luminosity GRB (1049 erg s‑1) with a structured jet.

  1. Analytical Aerodynamic Simulation Tools for Vertical Axis Wind Turbines

    International Nuclear Information System (INIS)

    Deglaire, Paul

    2010-01-01

    Wind power is a renewable energy source that is today the fastest growing solution to reduce CO 2 emissions in the electric energy mix. Upwind horizontal axis wind turbine with three blades has been the preferred technical choice for more than two decades. This horizontal axis concept is today widely leading the market. The current PhD thesis will cover an alternative type of wind turbine with straight blades and rotating along the vertical axis. A brief overview of the main differences between the horizontal and vertical axis concept has been made. However the main focus of this thesis is the aerodynamics of the wind turbine blades. Making aerodynamically efficient turbines starts with efficient blades. Making efficient blades requires a good understanding of the physical phenomena and effective simulations tools to model them. The specific aerodynamics for straight bladed vertical axis turbine flow are reviewed together with the standard aerodynamic simulations tools that have been used in the past by blade and rotor designer. A reasonably fast (regarding computer power) and accurate (regarding comparison with experimental results) simulation method was still lacking in the field prior to the current work. This thesis aims at designing such a method. Analytical methods can be used to model complex flow if the geometry is simple. Therefore, a conformal mapping method is derived to transform any set of section into a set of standard circles. Then analytical procedures are generalized to simulate moving multibody sections in the complex vertical flows and forces experienced by the blades. Finally the fast semi analytical aerodynamic algorithm boosted by fast multipole methods to handle high number of vortices is coupled with a simple structural model of the rotor to investigate potential aeroelastic instabilities. Together with these advanced simulation tools, a standard double multiple streamtube model has been developed and used to design several straight bladed

  2. Serotonin, tryptophan metabolism and the brain-gut-microbiome axis.

    Science.gov (United States)

    O'Mahony, S M; Clarke, G; Borre, Y E; Dinan, T G; Cryan, J F

    2015-01-15

    The brain-gut axis is a bidirectional communication system between the central nervous system and the gastrointestinal tract. Serotonin functions as a key neurotransmitter at both terminals of this network. Accumulating evidence points to a critical role for the gut microbiome in regulating normal functioning of this axis. In particular, it is becoming clear that the microbial influence on tryptophan metabolism and the serotonergic system may be an important node in such regulation. There is also substantial overlap between behaviours influenced by the gut microbiota and those which rely on intact serotonergic neurotransmission. The developing serotonergic system may be vulnerable to differential microbial colonisation patterns prior to the emergence of a stable adult-like gut microbiota. At the other extreme of life, the decreased diversity and stability of the gut microbiota may dictate serotonin-related health problems in the elderly. The mechanisms underpinning this crosstalk require further elaboration but may be related to the ability of the gut microbiota to control host tryptophan metabolism along the kynurenine pathway, thereby simultaneously reducing the fraction available for serotonin synthesis and increasing the production of neuroactive metabolites. The enzymes of this pathway are immune and stress-responsive, both systems which buttress the brain-gut axis. In addition, there are neural processes in the gastrointestinal tract which can be influenced by local alterations in serotonin concentrations with subsequent relay of signals along the scaffolding of the brain-gut axis to influence CNS neurotransmission. Therapeutic targeting of the gut microbiota might be a viable treatment strategy for serotonin-related brain-gut axis disorders. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. The manufacturing and metrology of off-axis mirrors

    Science.gov (United States)

    Penzkofer, Karlheinz; Rascher, Rolf; Küpper, Lutz; Liebl, Johannes

    2015-10-01

    Especially in the area of the large mirror manufacturing only a few manufacturers are capable to produce optical surfaces of high quality. Therefore a deterministic process should be developed in the project IFasO. In the field of telescope optics off-axis optical systems are becoming increasingly important. These systems try to avoid an obstructing of the incoming light by moving the secondary mirror out of the primary mirror's optical axis. This advantage leads to an increasing market for this type of optical surface. Until now off-axis mirrors were difficult or almost impossible to produce. With the processes developed in IFasO, high quality mirrors become possible. For this reason, this paper describes the manufacturing of off-axis surfaces and its problems. The mirror production used in the project IFasO is based on the specific design of the CNC center developed by the company Optotech. This center UPG2000 is capable of grinding, polishing, sagitta measurement and interferometric measurement in one mounting of the specimen. Usually a large optics has to be transported during their manufacturing after every individual process step. There is always a risk of damage of the specimen. The exact orientation of the surface relatively to the tool position is also required. This takes a huge amount of time and makes up most of the production time. In this presentation the use of UPG2000 and the next steps within the process development are described. In the current status the manufacturing of large off-axis elements with a PV < λ/10 rms is reproducible.

  4. Total Flavonoids Extracted from Xiaobuxin-Tang on the Hyperactivity of Hypothalamic-Pituitary-Adrenal Axis in Chronically Stressed Rats

    Directory of Open Access Journals (Sweden)

    Lei An

    2011-01-01

    Full Text Available Our previous studies have demonstrated that the total flavonoids (XBXT-2 isolated from the extract of Xiaobuxin-Tang (XBXT, a traditional Chinese herbal decoction, ameliorated behavioral alterations and hippocampal dysfunctions in chronically stressed rats. Studies over the last decades have suggested that the hyperactivity of hypothalamic-pituitary-adrenal (HPA axis is one of the most consistent findings in stress-related depression. Herein, we used the same chronic mild stress model of rats as before to further investigate the effect of XBXT-2 on the hyperactivity of HPA axis, including the stress hormones levels and glucocorticoid receptors (GRs expression. Our ELISA results showed that chronic administration of XBXT-2 (25, 50 mg kg−1, p.o., 28 days, the effective doses for behavioral responses significantly decreased serum corticosterone level and its upstream stress hormone adrenocorticotropic hormone (ACTH level in chronically stressed rats. Furthermore, western blotting result demonstrated XBXT-2 treatment ameliorated stress-induced decrease of GRs expression in hippocampus, an important target involved in the hyperactivity of HPA axis. These results were similar to that of classic antidepressant imipramine treatment (10 mg kg−1, p.o.. In conclusion, the modulation of HPA axis produced by XBXT-2, including the inhibition of stress hormones levels and up-regulation of hippocampal GRs expression, may be an important mechanism underlying its antidepressant-like effect in chronically stressed rats.

  5. Extraction of left-ventricular torsion angle from the long-axis view by block-matching algorithm: Comparison with the short-axis view.

    Science.gov (United States)

    Arab-Baferani, Zahra; Mokhtari-Dizaji, Manijhe; Roshanali, Farideh

    2013-02-01

    Due to limitations in measuring the torsion angle in the short-axis view when studying through-plane motion and so it is dependent on reference levels, in this study, we follow myocardial movement along the long-axis of the left ventricle (LV). Then, LV torsion is estimated in the long-axis view and compared with LV torsion in the short-axis view. Two dimensional echocardiographic images of healthy persons were recorded in cine loop format position throughout four cardiac cycles at basal and apical levels in the long- and short-axis views. The motion vectors for reign of interest in the horizontal and vertical directions were obtained by block matching algorithm. Correlation between the values of automated analysis and manual tracing was performed by Pearson correlation analysis. Then, the maximum rotation angles of the short- and long-axis views at basal and apical levels were assessed. Left-ventricular torsion angles in short-axis and long-axis views were calculated and compared based on rotation angles. There was a high correlation between the measured myocardial wall displacement of automated analysis (BM algorithm) and manual tracing (R=0.96, p<0.05). The maximum rotation angles of basal and apical levels in the short-axis view are 7.96±1.57° and 9.49±1.72° and so in the long-axis view are 18.51±3.41° and 14.74±2.91°, respectively. The LV torsion angles and the time to reach peak LV torsion angles in the short-axis views are 17.26±2.53°, 293±26ms and in the long-axis view are 32.26±5.60° and 290±22ms respectively. There was a high correlation between the left-ventricular torsion angle in the short-axis view and the long-axis view (R=0.92, p<0.05). There was also a high correlation between the time to reach peak left-ventricular torsion angle in the short-axis view as compared to the long-axis view (R=0.97, p<0.05). This study suggested that the LVtorsion angles in the short- and long-axis views were significantly correlated. It is concluded that

  6. Wearable Conductive Fiber Sensors for Multi-Axis Human Joint Angle Measurements

    Directory of Open Access Journals (Sweden)

    Asada H Harry

    2005-03-01

    Full Text Available Abstract Background The practice of continuous, long-term monitoring of human joint motion is one that finds many applications, especially in the medical and rehabilitation fields. There is a lack of acceptable devices available to perform such measurements in the field in a reliable and non-intrusive way over a long period of time. The purpose of this study was therefore to develop such a wearable joint monitoring sensor capable of continuous, day-to-day monitoring. Methods A novel technique of incorporating conductive fibers into flexible, skin-tight fabrics surrounding a joint is developed. Resistance changes across these conductive fibers are measured, and directly related to specific single or multi-axis joint angles through the use of a non-linear predictor after an initial, one-time calibration. Because these sensors are intended for multiple uses, an automated registration algorithm has been devised using a sensitivity template matched to an array of sensors spanning the joints of interest. In this way, a sensor array can be taken off and put back on an individual for multiple uses, with the sensors automatically calibrating themselves each time. Results The wearable sensors designed are comfortable, and acceptable for long-term wear in everyday settings. Results have shown the feasibility of this type of sensor, with accurate measurements of joint motion for both a single-axis knee joint and a double axis hip joint when compared to a standard goniometer used to measure joint angles. Self-registration of the sensors was found to be possible with only a few simple motions by the patient. Conclusion After preliminary experiments involving a pants sensing garment for lower body monitoring, it has been seen that this methodology is effective for monitoring joint motion of the hip and knee. This design therefore produces a robust, comfortable, truly wearable joint monitoring device.

  7. Microbial genes, brain & behaviour - epigenetic regulation of the gut-brain axis.

    Science.gov (United States)

    Stilling, R M; Dinan, T G; Cryan, J F

    2014-01-01

    To date, there is rapidly increasing evidence for host-microbe interaction at virtually all levels of complexity, ranging from direct cell-to-cell communication to extensive systemic signalling, and involving various organs and organ systems, including the central nervous system. As such, the discovery that differential microbial composition is associated with alterations in behaviour and cognition has significantly contributed to establishing the microbiota-gut-brain axis as an extension of the well-accepted gut-brain axis concept. Many efforts have been focused on delineating a role for this axis in health and disease, ranging from stress-related disorders such as depression, anxiety and irritable bowel syndrome to neurodevelopmental disorders such as autism. There is also a growing appreciation of the role of epigenetic mechanisms in shaping brain and behaviour. However, the role of epigenetics in informing host-microbe interactions has received little attention to date. This is despite the fact that there are many plausible routes of interaction between epigenetic mechanisms and the host-microbiota dialogue. From this new perspective we put forward novel, yet testable, hypotheses. Firstly, we suggest that gut-microbial products can affect chromatin plasticity within their host's brain that in turn leads to changes in neuronal transcription and eventually alters host behaviour. Secondly, we argue that the microbiota is an important mediator of gene-environment interactions. Finally, we reason that the microbiota itself may be viewed as an epigenetic entity. In conclusion, the fields of (neuro)epigenetics and microbiology are converging at many levels and more interdisciplinary studies are necessary to unravel the full range of this interaction. © 2013 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  8. Development of the adrenal axis in the neonatal rat

    Energy Technology Data Exchange (ETDEWEB)

    Guillet, Ronnie [Univ. of Rochester, NY (United States)

    1977-01-01

    Plasma corticosterone and ACTH concentrations were determined in neonatal rats 1, 7, 14, and 21 days old, under a variety of experimental conditions, to obtain more information on the postnatal development of the rat hypothalamo-adrenal (HHA) axis. The results indicate that: (1) there is a diminution followed by an increase in responsiveness of the adrenal gland, but the pituitary response to direct hormonal stimulation is unchanged during the first three postnatal weeks; (2) continued stimulation of the adrenal by ACTH or of the central nervous system (CNS) or hypothalamus by corticosterone is necessary during early postnatal development to allow normal maturation of the HHA axis; and (3) feedback inhibition is operative by birth, at least to a moderate degree. Taken together, the studies suggest that both the adrenal and pituitary glands are potentially functional at birth, but that the hypothalamic and CNS mediators of the stress response are not mature until at least the second or third postnatal week. (ERB)

  9. The on axis coupled structure type RF gun

    CERN Document Server

    Oda, F; Nakayama, A; Tanabe, E

    1999-01-01

    The fundamental design of this newly developed RF gun with a thermionic cathode is the pi/2 mode standing wave structure. It has two accelerating cells and a coupling cell located on the beam axis, a so-called on axis coupled structure (OCS). This structure offers a stable operation for high beam current, owing to high group velocity and wide bandwidth. It is important to reduce damage onto the cathode caused by back bombardment, especially for long macropulse operation, such as in an FEL injector. Back bombardment, as well as output beam profile was simulated by using the electromagnetic field analytical codes 'EMSYS'(2D) and 'MAFIA'(3D). The cavity shape was optimized to reduce back bombardment power without sacrificing beam emittance.

  10. APS-U LATTICE DESIGN FOR OFF-AXIS ACCUMULATION

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Yipeng; Borland, M.; Lindberg, R.; Sajaev, V.

    2017-06-25

    A 67-pm hybrid-seven-bend achromat (H7BA) lattice is being proposed for a future Advanced Photon Source (APS) multi-bend-achromat (MBA) upgrade project. This lattice design pushes for smaller emittance and requires use of a swap-out (on-axis) injection scheme due to limited dynamic acceptance. Alternate lattice design work has also been performed for the APS upgrade to achieve better beam dynamics performance than the nominal APS MBA lattice, in order to allow off-axis accumulation. Two such alternate H7BA lattice designs, which target a still-low emittance of 90 pm, are discussed in detail in this paper. Although the single-particle-dynamics performance is good, simulations of collective effects indicate that surprising difficulty would be expected accumulating high single-bunch charge in this lattice. The brightness of the 90-pm lattice is also a factor of two lower than the 67-pm H7BA lattice.

  11. Three-axis neutron spectrometer on the IWW-2 reactor

    International Nuclear Information System (INIS)

    Bobrovskij, V.I.; Goshchitskij, B.N.; Mirmel'shtejn, A.V.; Mikha lov, Yu.N.; Ponosov, Yu.S.

    1977-01-01

    A three-axis neutron spectrometer providing for the possibility to change smoothly the neutron scattering angle in the course of measurement was manufactured for studying the dynamics (frequencies and life time of phonons) of a crystalline lattice. This permits to use methods of constant energy and momentum transfer at fixed incident wave length in the scattering angle range of up to 100 deg. Major attention was given to such a substantial characteristic of the three-axis spectrometer as the spectrometer resolution function, which was determined experimentally and theoretically. A knowledge of that function permitted to make a sufficiently exact account of focusing effects when measuring neutron resonance, and to determine the instrumental widths of the resonances observed. A crystal incorporating a helium and nitrogen vessel was made for measurements in the 300-20 K range. A system of protective copper shields surrounding the helium vessel and a sample permits to operate without refilling helium for about 30 hr

  12. Psychiatric Axis I Comorbidities among Patients with Gender Dysphoria

    Directory of Open Access Journals (Sweden)

    Azadeh Mazaheri Meybodi

    2014-01-01

    Full Text Available Objectives. Cooccurring psychiatric disorders influence the outcome and prognosis of gender dysphoria. The aim of this study is to assess psychiatric comorbidities in a group of patients. Methods. Eighty-three patients requesting sex reassignment surgery (SRS were recruited and assessed through the Persian Structured Clinical Interview for DSM-IV Axis I disorders (SCID-I. Results. Fifty-seven (62.7% patients had at least one psychiatric comorbidity. Major depressive disorder (33.7%, specific phobia (20.5%, and adjustment disorder (15.7% were the three most prevalent disorders. Conclusion. Consistent with most earlier researches, the majority of patients with gender dysphoria had psychiatric Axis I comorbidity.

  13. Application of one-axis sun tracking system

    International Nuclear Information System (INIS)

    Sefa, Ibrahim; Demirtas, Mehmet; Colak, Ilhami

    2009-01-01

    This paper introduces design and application of a novel one-axis sun tracking system which follows the position of the sun and allows investigating effects of one-axis tracking system on the solar energy in Turkey. The tracking system includes a serial communication interface based on RS 485 to monitor whole processes on a computer screen and to plot data as graphic. In addition, system parameters such as the current, the voltage and the panel position have been observed by means of a microcontroller. The energy collected is measured and compared with a fixed solar system for the same solar panel. The results show that the solar energy collected on the tracking system is considerably much efficient than the fixed system. The tracking system developed in this study provides easy installation, simple mechanism and less maintenance.

  14. Effects of structure flexibility on horizontal axis wind turbine performances

    Science.gov (United States)

    Coiro, D. P.; Daniele, E.; Scherillo, F.

    2013-10-01

    This work illustrates the effects of flexibility of rotor blades and turbine tower on the performances of an horizontal axis wind turbine (HAWT) designed by our ADAG research group, by means of several example applied on a recent project for a active pitch controlled upwind 60 kW HAWT. The influence of structural flexibility for blade only, tower only and blade coupled with tower configuration is investigated using an aero-elastic computer-aided engineering (CAE) tool for horizontal axis wind turbines named FAST developed at National Renewable Energy Laboratory (NREL) of USA. For unsteady inflow conditions in front of the isolated HAWT the performances in rigid and flexible operation mode are computed and compared in order to illustrate the limitation included within a classical rigid body approach to wind turbine simulation.

  15. Spin squeezing in a generalized one-axis twisting model

    Science.gov (United States)

    Jin, Guang-Ri; Liu, Yong-Chun; Liu, Wu-Ming

    2009-07-01

    We investigate the dependence of spin squeezing on the polar angle of the initial coherent spin state |θ0, phi0rang in a generalized one-axis twisting model, where the detuning δ is taken into account. We show explicitly that regardless of δ and phi0, previous results of the ideal one-axis twisting are recovered as long as θ0=π/2. For a small departure of θ0 from π/2, however, the achievable variance (V -)min ~N2/3, which is larger than the ideal case N1/3. We also find that the maximal squeezing time tmin scales as N-5/6. Analytic expressions of (V-)min and tmin are presented and they agree with numerical simulations.

  16. Development of a Single-Axis Edge Detection System

    Energy Technology Data Exchange (ETDEWEB)

    Hanshaw, R.A.

    2000-02-18

    A SIP (Societe Genevoise d'Instruments de Physique) Trioptic coordinate measuring machine was modified for calibration of high quality single-axis glass standards to an uncertainty of {+-}0.000020 inch. The modification was accomplished through the addition of a frame grabber board, vision software, a high-resolution camera, stepper motors, a two-axis motor controller, and an HP-IB interface card. An existing temperature system (hygrometer, barometer, laser interferometer system, and optics) was retained as part of the system. An existing Hewlett Packard computer was replaced with a personal computer to accommodate the frame grabber board. Each component was integrated into the existing system using Visual Basic. The system was automated for unattended measurements by creating a machine programming language, which is recognized within the main program.

  17. Development of triple axis neutron spectrometer (Paper No. 24)

    International Nuclear Information System (INIS)

    Pal, B.C.; Wadhwa, N.R.; Goveas, S.H.

    1987-02-01

    The triple axis neutron spectrometers are the basic instruments intended for use with neutron beams from reactors. Various types of spectrometers, each devoted to different kinds of measurement can be designed and manufactured, once a prototype having all the attributes of a versatile instrument is designed and developed. With the view to achieving self reliance in this field, Central Workshops of Bhabha Atomic Research Centre (BARC), Bombay designed and developed a prototype of triple axis spectrometer meeting the specifications prepared by Nuclear Physics Division of BARC . This spectrometer, with a moving wedge system was successfully manufactured and installed at 'DHRUVA'. Another version of this spectrometer, called the 'Polarised Neutron Spectrometer' was also built and exported to South Korea and installed at Korea Advanced Energy Research Institute, Seoul. This paper deals with basic concept, development of design, engineering of mechanical assemblies, the manufacturing approach and problems encountered during manufacture. (author). 3 figs

  18. Efficiency of the DOMUS 750 vertical-axis wind turbine

    Science.gov (United States)

    Hallock, Kyle; Rasch, Tyler; Ju, Guoqiang; Alonso-Marroquin, Fernando

    2017-06-01

    The aim of this paper is to present some preliminary results on the efficiency of a wind turbine for an off-grid housing unit. To generate power, the unit uses a photovoltaic solar array and a vertical-axis wind turbine (VAWT). The existing VAWT was analysed to improve efficiency and increase power generation. There were found to be two main sources of inefficiency: 1. the 750W DC epicyclic generator performed poorly in low winds, and 2. the turbine blades wobbled, allowing for energy loss due to off-axis rotation. A 12V DC permanent magnet alternator was chosen that met the power requirements of the housing unit and would generate power at lower wind speeds. A support bracket was designed to prevent the turbine blades from wobbling.

  19. From Bench to Bedside: Translating the Prolactin/Vasoinhibin Axis

    Directory of Open Access Journals (Sweden)

    Jakob Triebel

    2017-12-01

    Full Text Available The prolactin/vasoinhibin axis defines an endocrine system, in which prolactin (PRL and vasoinhibins regulate blood vessel growth and function, the secretion of other hormones, inflammatory and immune processes, coagulation, and behavior. The core element of the PRL/vasoinhibin axis is the generation of vasoinhibins, which consists in the proteolytic cleavage of their precursor molecule PRL. Vasoinhibins can interact with multiple different partners to mediate their effects in various tissues and anatomical compartments, indicating their pleiotropic nature. Based on accumulating knowledge about the PRL/vasoinhibin axis, two clinical trials were initiated, in which vasoinhibin levels are the target of therapeutic interventions. One trial investigates the effect of levosulpiride, a selective dopamine D2-receptor antagonist, on retinal alterations in patients with diabetic macular edema and retinopathy. The rationale of this trial is that the levosulpiride-induced hyperprolactinemia resulting in increased retinal vasoinhibins could lead to beneficiary outcomes in terms of a vasoinhibin-mediated antagonization of diabetes-induced retinal alterations. Another trial investigated the effect of bromocriptine, a dopamine D2-receptor agonist, for the treatment of peripartum cardiomyopathy. The rationale of treatment with bromocriptine is the inhibition of vasoinhibin generation by substrate depletion to prevent detrimental effects on the myocardial microvascularization. The trial demonstrated that bromocriptine treatment was associated with a high rate of left ventricular recovery and low morbidity and mortality. Therapeutic interventions into the PRL/vasoinhibin axis bear the risk of side effects in the areas of blood coagulation, blood pressure, and alterations of the mental state.

  20. Hysteresis Motor Driven One Axis Magnetically Suspended Reaction Sphere

    OpenAIRE

    Zhou, Lei; Nejad, Mohammad Imani; Trumper, David L.

    2014-01-01

    The Attitude and Orbit Control System (AOCS) plays an essential role in the flight control of a spacecraft. This system usually contains a minimum of three reaction wheels (often 4-5 wheels are used for optimization and redundancy). By accelerating the appropriate wheels, the system can produce a zero-mean reaction torque about any axis to the spacecraft, which enables the spacecraft to maneuver on orbit. Meanwhile, the momentum generated by acceleration can be stored in the wheels.

  1. Targeting the Ron-DEK Signaling Axis in Breast Cancer

    Science.gov (United States)

    2014-09-01

    2014.173 INTRODUCTION Despite high survival rates for early-stage breast cancer , it is still the second leading cause of cancer - related deaths in the...164: 285–293. 37 Adams AK, Hallenbeck GE, Casper KA, Patil YJ, Wilson KM, Kimple RJ et al. DEK promotes HPV -positive and -negative head and neck cancer ...AWARD NUMBER: W81XWH-12-1-0194 TITLE: Targeting the Ron-DEK Signaling Axis in Breast Cancer PRINCIPAL INVESTIGATORS: Dr

  2. Inelastic scattering using the three-axis spectrometer technique

    International Nuclear Information System (INIS)

    Currat, R.

    1999-01-01

    The three-axis technique is a basic neutron scattering technique for inelastic work on single-crystal specimens. There is, at the moment, a fair degree of complementarity between TAS instruments on steady-state sources and TOF instruments on steady-state or pulsed sources. The technique is described, the issue of TAS versus TOF method is discussed, and investigations relating to the resolution functions are presented. (K.A.)

  3. Gut-Brain Axis in Gastric Mucosal Damage and Protection.

    Science.gov (United States)

    Sgambato, Dolores; Capuano, Annalisa; Sullo, Maria Giuseppa; Miranda, Agnese; Federico, Alessandro; Romano, Marco

    2016-01-01

    The gut-brain axis plays a potential role in numerous physiological and pathological conditions. Several substances link stomach with central nervous system. In particular, hypothalamo-pituitary-adrenocortical axis, thyrotropinreleasing factor-containing nerve fibers and capsaicin-sensitive nerves are principal mediators of the harmful and protective central nervous system-mediated effects on gastric mucosa. Also, existing evidence indicates that nitric oxide, prostaglandins and calcitonin gene-related peptide play a role as final effectors of gastric protection. We undertook a structured search of bibliographic databases for peerreviewed research literature with the aim of focusing on the role of gut-brain axis in gastric damage and protection. In particular, we examined manuscripts dealing with the role of steroids, thyrotropin-releasing hormone, prostaglandins, melatonin, hydrogen sulfide and peptides influencing food intake (i.e. leptin, cholecystokinin, peptide YY, central glucagon-like peptide-1, and ghrelin). Also, the role of GABAergic and glutamatergic pathways in gastric mucosal protection have been examined. We found and reviewed 61 peer-reviewed papers dealing with the major aspects related to the role of gut brain axis in gastric mucosal damage and protection. A dense neuronal network links stomach with central nervous system and a number of neurotransmitters and peptides functionally and anatomically related to central nervous system play a major role in contributing to gastric mucosal integrity. Exploiting the mechanisms underlying the connection between brain and gut may lead to a better understanding of the pathophysiology of gastric mucosal injury and to an improvement in the prevention and, eventually, management of gastric damage.

  4. Glycation & the RAGE axis: targeting signal transduction through DIAPH1.

    Science.gov (United States)

    Shekhtman, Alexander; Ramasamy, Ravichandran; Schmidt, Ann Marie

    2017-02-01

    The consequences of chronic disease are vast and unremitting; hence, understanding the pathogenic mechanisms mediating such disorders holds promise to identify therapeutics and diminish the consequences. The ligands of the receptor for advanced glycation end products (RAGE) accumulate in chronic diseases, particularly those characterized by inflammation and metabolic dysfunction. Although first discovered and reported as a receptor for advanced glycation end products (AGEs), the expansion of the repertoire of RAGE ligands implicates the receptor in diverse milieus, such as autoimmunity, chronic inflammation, obesity, diabetes, and neurodegeneration. Areas covered: This review summarizes current knowledge regarding the ligand families of RAGE and data from human subjects and animal models on the role of the RAGE axis in chronic diseases. The recent discovery that the cytoplasmic domain of RAGE binds to the formin homology 1 (FH1) domain, DIAPH1, and that this interaction is essential for RAGE ligand-stimulated signal transduction, is discussed. Finally, we review therapeutic opportunities targeting the RAGE axis as a means to mitigate chronic diseases. Expert commentary: With the aging of the population and the epidemic of cardiometabolic disease, therapeutic strategies to target molecular pathways that contribute to the sequelae of these chronic diseases are urgently needed. In this review, we propose that the ligand/RAGE axis and its signaling nexus is a key factor in the pathogenesis of chronic disease and that therapeutic interruption of this pathway may improve quality and duration of life.

  5. l=1 helical axis heliotron device in Kyoto university

    International Nuclear Information System (INIS)

    Nagasaki, K.; Sano, F.; Mizuuchi, T.; Hanatani, K.; Okada, H.; Obiki, T.

    1999-01-01

    Helical systems are an attractive candidate for magnetic fusion reactor. Recently, there has been great progress in theoretical research of three dimensional magnetic field structures, resulting in several kinds of confinement optimization being proposed for toroidal magnetic confinement system. For example, some sophisticated ideas have appeared on stage such as quasi-helical symmetry and quasi-isodynamic system. To find experimentally which way is the best Optimisation, a new helical axis heliotron device, so called 'Heliotron J', is under construction in the Institute of Advanced Energy, Kyoto University, Japan. In this conference, the basic concept and the present status will be presented. In the conventional plane axis helical system, it was difficult to have both good particle confinement and good MHD stability simultaneously. The goal of Heliotron J project is to clarify their compatibility in the spatial axis toroidal device. The best way for Optimising the helical magnetic field configuration will be explored by investigating the plasma response to the change in the field components. The main subjects for plasma experiment are: demonstration of the existence of good magnetic flux surfaces, reduction of neoclassical transport in collisionless regime, MHD Stabilisation in high β plasma, controllability of bootstrap current, good confinement of high energy particles

  6. MARRT: Medial Axis biased rapidly-exploring random trees

    KAUST Repository

    Denny, Jory

    2014-05-01

    © 2014 IEEE. Motion planning is a difficult and widely studied problem in robotics. Current research aims not only to find feasible paths, but to ensure paths have certain properties, e.g., shortest or safest paths. This is difficult for current state-of-the-art sampling-based techniques as they typically focus on simply finding any path. Despite this difficulty, sampling-based techniques have shown great success in planning for a wide range of applications. Among such planners, Rapidly-Exploring Random Trees (RRTs) search the planning space by biasing exploration toward unexplored regions. This paper introduces a novel RRT variant, Medial Axis RRT (MARRT), which biases tree exploration to the medial axis of free space by pushing all configurations from expansion steps towards the medial axis. We prove that this biasing increases the tree\\'s clearance from obstacles. Improving obstacle clearance is useful where path safety is important, e.g., path planning for robots performing tasks in close proximity to the elderly. Finally, we experimentally analyze MARRT, emphasizing its ability to effectively map difficult passages while increasing obstacle clearance, and compare it to contemporary RRT techniques.

  7. Searching for cosmological preferred axis using cosmographic approach

    Science.gov (United States)

    Salehi, Amin; Setare, Mohammad Reza

    2017-12-01

    Recent released Planck data and other astronomical observations show that the universe may be anisotropic on large scales. This hints a cosmological privileged axis in our anisotropic expanding universe. This paper proceeds a modified redshift in anisotropic cosmological model as 1+\\tilde{z}(t,\\hat{{p})=a(t_{0)}/a(t)(1-A(\\hat{n}.\\hat{p})) (where A is the magnitude of anisotropy, \\hat{n} is the direction of privileged axis, and \\hat{p} is the direction of each SNe Ia sample to galactic coordinates) along with anisotropic parameter δ =A(\\hat{n}.\\hat{p})/1+A(\\hat{n.\\hat{p})}. The luminosity distance is expanded with model-independent cosmographic parameters as a function of modified redshift \\tilde{z}. As the transformation matrix M(n× n) is obtained to convert the Taylor series coefficients of isotropic luminosity distance to corresponding anisotropic parameters. These results culminate the magnitude of anisotropy about \\mid A\\mid ˜eq 10^{-3} and the direction of preferred axis as (l,b)=( 297^{-34}_{+34},3^{-28}_{+28}) , which are consistent with other studies in 1-σ confidence level.

  8. A Dual-Axis Electrostatically Driven MEMS Microgripper

    Directory of Open Access Journals (Sweden)

    Yukun Jia

    2014-11-01

    Full Text Available This paper presents the design of a new monolithic two-axis electrostatically actuated MEMS microgripper with integrated capacitive position and force sensors working at the micro-scale level. Each of the two jaws of the microgripper possesses two degrees-of-freedom (DOF and is capable of positioning in both x-and y-axes. Unlike existing works, where one gripper arm is actuated and other one is sensed, both arms of the proposed microgripper are actuated and sensed independently. A sensing scheme is constructed to provide the position and force signals in the noncontact and contact phases, respectively. By applying a 120V driving voltage, the jaw can provide 70 μm x-axis and 18 μm y-axis displacements with the force of 190 μN. By this design, the real-time position and grasping force information can be obtained in the dual sensing mode. Both analytical calculation and finite-element analysis (FEA were performed to verify the performance of the proposed design. A scaled-up prototype is designed, fabricated and tested through the experiment to verify the structure design of the microgripper.

  9. Analytical Methods of Decoupling the Automotive Engine Torque Roll Axis

    Science.gov (United States)

    JEONG, TAESEOK; SINGH, RAJENDRA

    2000-06-01

    This paper analytically examines the multi-dimensional mounting schemes of an automotive engine-gearbox system when excited by oscillating torques. In particular, the issue of torque roll axis decoupling is analyzed in significant detail since it is poorly understood. New dynamic decoupling axioms are presented an d compared with the conventional elastic axis mounting and focalization methods. A linear time-invariant system assumption is made in addition to a proportionally damped system. Only rigid-body modes of the powertrain are considered and the chassis elements are assumed to be rigid. Several simplified physical systems are considered and new closed-form solutions for symmetric and asymmetric engine-mounting systems are developed. These clearly explain the design concepts for the 4-point mounting scheme. Our analytical solutions match with the existing design formulations that are only applicable to symmetric geometries. Spectra for all six rigid-body motions are predicted using the alternate decoupling methods and the closed-form solutions are verified. Also, our method is validated by comparing modal solutions with prior experimental and analytical studies. Parametric design studies are carried out to illustrate the methodology. Chief contributions of this research include the development of new or refined analytical models and closed-form solutions along with improved design strategies for the torque roll axis decoupling.

  10. [A cadaveric study of relationships among rotational alignment reference axes of distal femur and tibial mechanical axis].

    Science.gov (United States)

    Zhao, Bao-hui; Chen, Bai-cheng; Shao, De-cheng; Wang, Fei; Gao, Shi-jun; Lu, Bo

    2008-07-15

    To investigate the relationships among rotational alignment reference axes of distal femur and tibial mechanical axis, and determine the safest rotational alignment reference axis. Digital photos were taken of 30 cadaveric lower extremities with knee in extension and flexion at 90 degrees , angles were measured among tibial mechanical axis and a line perpendicular to clinical epicondylar axis, a line perpendicular to surgical epicondylar axis, Whiteside's line and femoral mechanical axis. Statistical analysis of relationships among those axes were performed. The angles among the tibial mechanical axis and a line perpendicular to the clinical epicondylar axis, a line perpendicular to the surgical epicondylar axis, Whiteside's line and femoral mechanical axis were 0.6 degrees varus, 3.9 degrees varus, 0.2 degrees valgus and 3.0 degrees varus respectively. The angle between the femoral mechanical axis and the tibial mechanical axis was significantly larger than the angles among the tibial mechanical axis and a line perpendicular to the clinical epicondylar axis, the Whiteside's line (P axis and the tibial mechanical axis. Angles of the clinical epicondylar axis, the surgical epicondylar axis and the Whiteside's line between knee extension and flexion were 2.3 degrees valgus, 0.9 degrees varus and 3.1 degrees valgus respectively. The surgical epicondylar axis rather than the clinical epicondylar axis or the Whiteside's line is the safest femoral rotational alignment reference axis intraoperatively.

  11. HGF/c-MET Axis in Tumor Microenvironment and Metastasis Formation

    Directory of Open Access Journals (Sweden)

    Anna Spina

    2015-01-01

    Full Text Available Tumor metastases are responsible for approximately 90% of all cancer-related deaths. Metastasis formation is a multistep process that requires acquisition by tumor cells of a malignant phenotype that allows them to escape from the primary tumor site and invade other organs. Each step of this mechanism involves a deep crosstalk between tumor cells and their microenvironment where the host cells play a key role in influencing metastatic behavior through the release of many secreted factors. Among these signaling molecules, Hepatocyte Growth Factor (HGF is released by many cell types of the tumor microenvironment to target its receptor c-MET within the cells of the primary tumor. Many studies reveal that HGF/c-MET axis is implicated in various human cancers, and genetic and epigenetic gain of functions of this signaling contributes to cancer development through a variety of mechanisms. In this review, we describe the specific types of cells in the tumor microenvironment that release HGF in order to promote the metastatic outgrowth through the activation of extracellular matrix remodeling, inflammation, migration, angiogenesis, and invasion. We dissect the potential use of new molecules that interfere with the HGF/c-MET axis as therapeutic targets for future clinical trials in cancer disease.

  12. The Akt-mTOR axis is a pivotal regulator of eccentric hypertrophy during volume overload.

    Science.gov (United States)

    Ikeda, Masataka; Ide, Tomomi; Fujino, Takeo; Matsuo, Yuka; Arai, Shinobu; Saku, Keita; Kakino, Takamori; Oga, Yasuhiro; Nishizaki, Akiko; Sunagawa, Kenji

    2015-10-30

    The heart has two major modalities of hypertrophy in response to hemodynamic loads: concentric and eccentric hypertrophy caused by pressure and volume overload (VO), respectively. However, the molecular mechanism of eccentric hypertrophy remains poorly understood. Here we demonstrate that the Akt-mammalian target of rapamycin (mTOR) axis is a pivotal regulator of eccentric hypertrophy during VO. While mTOR in the heart was activated in a left ventricular end-diastolic pressure (LVEDP)-dependent manner, mTOR inhibition suppressed eccentric hypertrophy and induced cardiac atrophy even under VO. Notably, Akt was ubiquitinated and phosphorylated in response to VO, and blocking the recruitment of Akt to the membrane completely abolished mTOR activation. Various growth factors were upregulated during VO, suggesting that these might be involved in Akt-mTOR activation. Furthermore, the rate of eccentric hypertrophy progression was proportional to mTOR activity, which allowed accurate estimation of eccentric hypertrophy by time-integration of mTOR activity. These results suggested that the Akt-mTOR axis plays a pivotal role in eccentric hypertrophy, and mTOR activity quantitatively determines the rate of eccentric hypertrophy progression. As eccentric hypertrophy is an inherent system of the heart for regulating cardiac output and LVEDP, our findings provide a new mechanistic insight into the adaptive mechanism of the heart.

  13. Measurement of multiaxial ply strength by an off-axis flexure test

    Science.gov (United States)

    Crews, John H., Jr.; Naik, Rajiv A.

    1992-01-01

    An off-axis flexure (OAF) test was performed to measure ply strength under multiaxial stress states. This test involves unidirectional off-axis specimens loaded in bending, using an apparatus that allows these anisotropic specimens to twist as well as flex without the complications of a resisting torque. A 3D finite element stress analysis verified that simple beam theory could be used to compute the specimen bending stresses at failure. Unidirectional graphite/epoxy specimens with fiber angles ranging from 90 deg to 15 deg have combined normal and shear stresses on their failure planes that are typical of 45 deg plies in structural laminates. Tests for a range of stress states with AS4/3501-6 specimens showed that both normal and shear stresses on the failure plane influenced cracking resistance. This OAF test may prove to be useful for generating data needed to predict ply cracking in composite structures and may also provide an approach for studying fiber-matrix interface failures under stress states typical of structures.

  14. Structural Inheritance of the Actin Cytoskeletal Organization Determines the Body Axis in Regenerating Hydra.

    Science.gov (United States)

    Livshits, Anton; Shani-Zerbib, Lital; Maroudas-Sacks, Yonit; Braun, Erez; Keren, Kinneret

    2017-02-07

    Understanding how mechanics complement bio-signaling in defining patterns during morphogenesis is an outstanding challenge. Here, we utilize the multicellular polyp Hydra to investigate the role of the actomyosin cytoskeleton in morphogenesis. We find that the supra-cellular actin fiber organization is inherited from the parent Hydra and determines the body axis in regenerating tissue segments. This form of structural inheritance is non-trivial because of the tissue folding and dynamic actin reorganization involved. We further show that the emergence of multiple body axes can be traced to discrepancies in actin fiber alignment at early stages of the regeneration process. Mechanical constraints induced by anchoring regenerating Hydra on stiff wires suppressed the emergence of multiple body axes, highlighting the importance of mechanical feedbacks in defining and stabilizing the body axis. Together, these results constitute an important step toward the development of an integrated view of morphogenesis that incorporates mechanics. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  15. Maternal co-ordinate gene regulation and axis polarity in the scuttle fly Megaselia abdita.

    Science.gov (United States)

    Wotton, Karl R; Jiménez-Guri, Eva; Jaeger, Johannes

    2015-03-01

    Axis specification and segment determination in dipteran insects are an excellent model system for comparative analyses of gene network evolution. Antero-posterior polarity of the embryo is established through systems of maternal morphogen gradients. In Drosophila melanogaster, the anterior system acts through opposing gradients of Bicoid (Bcd) and Caudal (Cad), while the posterior system involves Nanos (Nos) and Hunchback (Hb) protein. These systems act redundantly. Both Bcd and Hb need to be eliminated to cause a complete loss of polarity resulting in mirror-duplicated abdomens, so-called bicaudal phenotypes. In contrast, knock-down of bcd alone is sufficient to induce double abdomens in non-drosophilid cyclorrhaphan dipterans such as the hoverfly Episyrphus balteatus or the scuttle fly Megaselia abdita. We investigate conserved and divergent aspects of axis specification in the cyclorrhaphan lineage through a detailed study of the establishment and regulatory effect of maternal gradients in M. abdita. Our results show that the function of the anterior maternal system is highly conserved in this species, despite the loss of maternal cad expression. In contrast, hb does not activate gap genes in this species. The absence of this activatory role provides a precise genetic explanation for the loss of polarity upon bcd knock-down in M. abdita, and suggests a general scenario in which the posterior maternal system is increasingly replaced by the anterior one during the evolution of the cyclorrhaphan dipteran lineage.

  16. Design of multi-energy Helds coupling testing system of vertical axis wind power system

    Science.gov (United States)

    Chen, Q.; Yang, Z. X.; Li, G. S.; Song, L.; Ma, C.

    2016-08-01

    The conversion efficiency of wind energy is the focus of researches and concerns as one of the renewable energy. The present methods of enhancing the conversion efficiency are mostly improving the wind rotor structure, optimizing the generator parameters and energy storage controller and so on. Because the conversion process involves in energy conversion of multi-energy fields such as wind energy, mechanical energy and electrical energy, the coupling effect between them will influence the overall conversion efficiency. In this paper, using system integration analysis technology, a testing system based on multi-energy field coupling (MEFC) of vertical axis wind power system is proposed. When the maximum efficiency of wind rotor is satisfied, it can match to the generator function parameters according to the output performance of wind rotor. The voltage controller can transform the unstable electric power to the battery on the basis of optimizing the parameters such as charging times, charging voltage. Through the communication connection and regulation of the upper computer system (UCS), it can make the coupling parameters configure to an optimal state, and it improves the overall conversion efficiency. This method can test the whole wind turbine (WT) performance systematically and evaluate the design parameters effectively. It not only provides a testing method for system structure design and parameter optimization of wind rotor, generator and voltage controller, but also provides a new testing method for the whole performance optimization of vertical axis wind energy conversion system (WECS).

  17. The brain-gut axis dysfunctions and hypersensitivity to food antigens in the etiopathogenesis of schizophrenia.

    Science.gov (United States)

    Karakuła-Juchnowicz, Hanna; Dzikowski, Michał; Pelczarska, Agnieszka; Dzikowska, Izabela; Juchnowicz, Dariusz

    2016-01-01

    Despite over 100-year history of research on schizophrenia, its etiology is still not fully understood, which might be due to the significant heterogeneity in terms of both its course, as well as the etiopathogenesis. One of the best-proven mediating mechanisms in the development of schizophrenia is the immuno-inflammatory response, the sources of which are believed to be the dysfunctions of brain-gut axis and pathological processes occurring in the intestines. This paper is a review of the literature on this subject which presents factors both involved in the functioning of brain-gut axis and important for the development of schizophrenia, i.e. 1. intestinal microbiome (intestinal microbiota), 2. permeable intestine (leaky gut syndrome), 3. hypersensitivity to food antigens, including gluten and casein of cow's milk. Research results seem to be very promising and indicate the possibility of improved clinical outcomes in some patients with schizophrenia by modifying diet, use of probiotics, and the implementation of antibiotic therapy of specific treatment groups. However, further research is needed on links between the intestinal microbiome and intestinal function as factors mediating the activation of the immune system and the development and further course of schizophrenia.

  18. Organizing Patient Involvement

    DEFF Research Database (Denmark)

    Brehm Johansen, Mette

    Patient involvement has become a part of the political agenda in Danish healthcare. Patients are to be involved not only in questions and decisions relating to their own treatment and care – to involve patients in quality improvement has also become a political expectation of quality work in Danish...... hospitals. During the last 25 years, patient involvement and quality improvement have become connected in Danish healthcare policy. However, the ideal of involving patients in quality improvement is described in very general terms and with only few specific expectations of how it is to be carried out...... in practice, as I show in the thesis. In the patient involvement literature, the difficulties of getting patient involvement in quality improvement to have in an impact on the planning and development of healthcare services is, for example, ascribed to conceptual vagueness of patient involvement, differences...

  19. Fast and accurate measurement of on-axis gain and on-axis polarization at a finite distance

    DEFF Research Database (Denmark)

    Pivnenko, S.; Breinbjerg, O.

    2013-01-01

    In this paper, a technique for fast and accurate measurement of on-axis gain and on-axis polarization characteristics of antennas, such as Standard Gain Horns, compact range feed horns, and near-field probes, is described. The proposed gain determination procedure is a modification of the far......-field substitution technique in which the measurement distance is defined between the phase centres of the antennas. The location of the phase centre of the antenna under test (AUT) is found from a quick pattern measurement consisting of only four cuts including the main and diagonal planes. Additionally, in order...... to reduce the amount of measurement data and thus measurement time, the phase centre location is found on a sparse frequency grid and the values in the intermediate points are found by interpolation. The antenna polarization is determined from the amplitude/phase frequency sweeps with two orthogonal AUT...

  20. Inflammation and gut-brain axis link obesity to cognitive dysfunction: plausible pharmacological interventions.

    Science.gov (United States)

    Solas, Maite; Milagro, Fermin I; Ramírez, María J; Martínez, J Alfredo

    2017-12-01

    Obesity prevalence is increasing steadily throughout the world's population in most countries and in parallel the prevalence of metabolic disorders including cardiovascular diseases and type 2 diabetes is also rising, but less is reported about excessive adiposity relationship with poorer cognitive performance, cognitive decline and dementia. Some human clinical studies have evidenced that obesity is related to the risk of the development of mild cognitive impairment, in the form of short-term memory and executive function deficits, as well as dementia and Alzheimer's disease. The precise mechanisms that underlie the connections between obesity and the risk of cognitive impairment are still largely unknown but potential avenues of further research include insulin resistance, the gut-brain axis, and systemic mediators and central inflammation processes. A common feature of metabolic diseases is a chronic and low-grade activation of the inflammatory system. This inflammation may eventually spread from peripheral tissue to the brain, and recent reports suggest that neuroinflammation is an important causal mechanism in cognitive decline. This inflammatory status could be triggered by changes in the gut microbiota composition. Consumption of diets high in fat and sugar influences the microbiota composition, which may lead to an imbalanced microbial population in the gut. Thus, it has recently been hypothesized that the gut microbiota could be part of a mechanistic link between the consumption of high fat and other unbalanced diets and impaired cognition, termed 'gut-brain axis'. The present review will aim at providing an integrative analysis of the effects of obesity and unbalanced diets on cognitive performance and discusses some of the potential mechanisms involved, namely inflammation and changes in gut-brain axis. Moreover, the review aims to analyze anti-inflammatory drugs that have been tested for the treatment of cognition and obesity, recently approved anti

  1. The Hypothalamic-Pituitary-Adrenal Axis, Obesity, and Chronic Stress Exposure: Sleep and the HPA Axis in Obesity

    OpenAIRE

    Lucassen, Eliane A.; Cizza, Giovanni

    2012-01-01

    Obesity, exposure to stress and inadequate sleep are prevalent phenomena in modern society. In this review we focus on their relationships and critically evaluate causality. In obese individuals, one of the main stress systems, the hypothalamic-pituitary-adrenal axis, is altered, and concentrations of cortisol are elevated in adipose tissue due to elevated local activity of 11β-hydroxysteroid dehydrogenase (HSD) type 1. Short sleep and decreased sleep quality are also associated with obesity....

  2. Lack of remorse in antisocial personality disorder: sociodemographic correlates, symptomatic presentation, and comorbidity with Axis I and Axis II disorders in the National Epidemiologic Survey on Alcohol and Related Conditions.

    Science.gov (United States)

    Goldstein, Risë B; Grant, Bridget F; Huang, Boji; Smith, Sharon M; Stinson, Frederick S; Dawson, Deborah A; Chou, S Patricia

    2006-01-01

    The purpose of this study was to compare sociodemographic and family history correlates, symptomatic presentation, and comorbidity with Axis I and Axis II disorders, in an epidemiologic sample of adults with DSM-IV antisocial personality disorder (ASPD) who lacked, vs those who did not lack, remorse. This study is based on a nationally representative sample of adults. Lifetime prevalences of each ASPD diagnostic criterion and each comorbid mood, anxiety, substance use, and personality disorder were estimated. Logistic regression was used to examine associations of lack of remorse with ASPD symptom patterns and comorbid disorders. Diagnoses were made using the National Institute on Alcohol Abuse and Alcoholism Alcohol Use Disorder and Associated Disabilities Interview Schedule-DSM-IV Version. Among the 1422 respondents with ASPD, 728 (51%) lacked remorse. Respondents who lacked remorse were younger and more often reported a family history of drug problems than those who did not. More often than remorse-positive respondents, those who were remorse-negative met diagnostic criteria involving violence against persons and less often met criteria involving offenses against property. Remorse was not associated with cruelty to animals, nor with most nonviolent antisocial behaviors. Remorse-negative respondents endorsed more total lifetime violent behaviors than those who were remorse-positive. Lack of remorse was not associated with any lifetime comorbid Axis I or Axis II disorder. Patterns of findings were generally similar between men and women. Lack of remorse appears to identify at best a modestly more symptomatically severe and violent form of ASPD in nonclinical populations.

  3. FAMILY HISTORY STUDY OF THE FAMILIAL COAGGREGATION OF BORDERLINE PERSONALITY DISORDER WITH AXIS I AND NON-BORDERLINE DRAMATIC CLUSTER AXIS II DISORDERS

    OpenAIRE

    Zanarini, Mary C.; Barison, Leah K.; Frankenburg, Frances R.; Reich, D. Bradford; Hudson, James I.

    2009-01-01

    The purpose of this study was to assess the familial coaggregation of borderline personality disorder (BPD) with a full array of axis I disorders and four axis II disorders (antisocial personality disorder, histrionic personality disorder, narcissistic personality disorder, and sadistic personality disorder) in the first-degree relatives of borderline probands and axis II comparison subjects. Four hundred and forty-five inpatients were interviewed about familial psychopathology using the Revi...

  4. The Simulation Study of Horizontal Axis Water Turbine Using Flow Simulation Solidworks Application

    Science.gov (United States)

    Prasetyo, H.; Budiana, EP; Tjahjana, DDDP; Hadi, S.

    2018-02-01

    The design of Horizontal Axis Water Turbine in pico hydro power plants involves many parameters. To simplify that, usually using computer simulation is applied. This research performs simulation process variation on turbine blade number, turbine blade curvature angle, turbine bucket angle and blocking system tilt angle. Those four variations were combined in order to obtain the best design of turbine. The study used Flow Simulation Solidworks application, and obtain data on turbine speed, pressure, force, and torque. However, this research focused on turbine torque value. The best design of turbine was obtained in the turbine with 6 blades, blade curvature angle of 65° and bucket angle of 10°, and blocking system tilt angle of 40°. In the best turbine, the produced torque value was 8.464 Nm.

  5. Impaired Sympathoadrenal Axis Function Contributes to Enhanced Insulin Secretion in Prediabetic Obese Rats

    Directory of Open Access Journals (Sweden)

    Ana Eliza Andreazzi

    2011-01-01

    Full Text Available The involvement of sympathoadrenal axis activity in obesity onset was investigated using the experimental model of treating neonatal rats with monosodium L-glutamate. To access general sympathetic nervous system activity, we recorded the firing rates of sympathetic superior cervical ganglion nerves in animals. Catecholamine content and secretion from isolated adrenal medulla were measured. Intravenous glucose tolerance test was performed, and isolated pancreatic islets were stimulated with glucose and adrenergic agonists. The nerve firing rate of obese rats was decreased compared to the rate for lean rats. Basal catecholamine secretion decreased whereas catecholamine secretion induced by carbachol, elevated extracellular potassium, and caffeine in the isolated adrenal medulla were all increased in obese rats compared to control. Both glucose intolerance and hyperinsulinaemia were observed in obese rats. Adrenaline strongly inhibited glucose-induced insulin secretion in obese animals. These findings suggest that low sympathoadrenal activity contributes to impaired glycaemic control in prediabetic obese rats.

  6. The PPARα - FGF21 hormone axis contributes to metabolic regulation by the hepatic JNK signaling pathway

    Science.gov (United States)

    Vernia, Santiago; Cavanagh-Kyros, Julie; Garcia-Haro, Luisa; Sabio, Guadalupe; Barrett, Tamera; Jung, Dae Young; Kim, Jason K.; Xu, Jia; Shulha, Hennady P.; Garber, Manuel; Gao, Guangping; Davis, Roger J.

    2014-01-01

    The cJun NH2-terminal kinase (JNK) stress signaling pathway is implicated in the metabolic response to the consumption of a high fat diet, including the development of obesity and insulin resistance. These metabolic adaptations involve altered liver function. Here we demonstrate that hepatic JNK potently represses the nuclear hormone receptor peroxisome proliferator-activated receptor α (PPARα). JNK therefore causes decreased expression of PPARα target genes that increase fatty acid oxidation / ketogenesis and promote the development of insulin resistance. We show that the PPARα target gene fibroblast growth factor 21 (Fgf21) plays a key role in this response because disruption of the hepatic PPARα - FGF21 hormone axis suppresses the metabolic effects of JNK-deficiency. This analysis identifies the hepatokine FGF21 as a critical mediator of JNK signaling in the liver. PMID:25043817

  7. Gut-central nervous system axis is a target for nutritional therapies

    Directory of Open Access Journals (Sweden)

    Pimentel Gustavo D

    2012-04-01

    Full Text Available Abstract Historically, in the 1950s, the chemist Linus Pauling established a relationship between decreased longevity and obesity. At this time, with the advent of studies involving the mechanisms that modulate appetite control, some researchers observed that the hypothalamus is the "appetite centre" and that peripheral tissues have important roles in the modulation of gut inflammatory processes and levels of hormones that control food intake. Likewise, the advances of physiological and molecular mechanisms for patients with obesity, type 2 diabetes mellitus, inflammatory bowel diseases, bariatric surgery and anorexia-associated diseases has been greatly appreciated by nutritionists. Therefore, this review highlights the relationship between the gut-central nervous system axis and targets for nutritional therapies.

  8. Effect of Relative Marker Movement on the Calculation of the Foot Torsion Axis Using a Combined Cardan Angle and Helical Axis Approach

    Science.gov (United States)

    Graf, Eveline S.; Wright, Ian C.; Stefanyshyn, Darren J.

    2012-01-01

    The two main movements occurring between the forefoot and rearfoot segment of a human foot are flexion at the metatarsophalangeal joints and torsion in the midfoot. The location of the torsion axis within the foot is currently unknown. The purpose of this study was to develop a method based on Cardan angles and the finite helical axis approach to calculate the torsion axis without the effect of flexion. As the finite helical axis method is susceptible to error due to noise with small helical rotations, a minimal amount of rotation was defined in order to accurately determine the torsion axis location. Using simulation, the location of the axis based on data containing noise was compared to the axis location of data without noise with a one-sample t-test and Fisher's combined probability score. When using only data with helical rotation of seven degrees or more, the location of the torsion axis based on the data with noise was within 0.2 mm of the reference location. Therefore, the proposed method allowed an accurate calculation of the foot torsion axis location. PMID:22666303

  9. Effect of Relative Marker Movement on the Calculation of the Foot Torsion Axis Using a Combined Cardan Angle and Helical Axis Approach

    Directory of Open Access Journals (Sweden)

    Eveline S. Graf

    2012-01-01

    Full Text Available The two main movements occurring between the forefoot and rearfoot segment of a human foot are flexion at the metatarsophalangeal joints and torsion in the midfoot. The location of the torsion axis within the foot is currently unknown. The purpose of this study was to develop a method based on Cardan angles and the finite helical axis approach to calculate the torsion axis without the effect of flexion. As the finite helical axis method is susceptible to error due to noise with small helical rotations, a minimal amount of rotation was defined in order to accurately determine the torsion axis location. Using simulation, the location of the axis based on data containing noise was compared to the axis location of data without noise with a one-sample t-test and Fisher's combined probability score. When using only data with helical rotation of seven degrees or more, the location of the torsion axis based on the data with noise was within 0.2 mm of the reference location. Therefore, the proposed method allowed an accurate calculation of the foot torsion axis location.

  10. Role of the endothelin axis in astrocyte- and endothelial cell-mediated chemoprotection of cancer cells

    Science.gov (United States)

    Kim, Seung Wook; Choi, Hyun Jin; Lee, Ho-Jeong; He, Junqin; Wu, Qiuyu; Langley, Robert R.; Fidler, Isaiah J.; Kim, Sun-Jin

    2014-01-01

    Background Recent evidence suggests that astrocytes protect cancer cells from chemotherapy by stimulating upregulation of anti-apoptotic genes in those cells. We investigated the possibility that activation of the endothelin axis orchestrates survival gene expression and chemoprotection in MDA-MB-231 breast cancer cells and H226 lung cancer cells. Methods Cancer cells, murine astrocytes, and murine fibroblasts were grown in isolation, and expression of endothelin (ET) peptides and ET receptors (ETAR and ETBR) compared with expression on cancer cells and astrocytes (or cancer cells and fibroblasts) that were co-incubated for 48 hours. Type-specific endothelin receptor antagonists were used to evaluate the contribution of ETAR and ETBR to astrocyte-induced activation of the protein kinase B (AKT)/mitogen-activated protein kinase (MAPK) signal transduction pathways, anti-apoptotic gene expression, and chemoprotection of cancer cells. We also investigated the chemoprotective potential of brain endothelial cells and microglial cells. Results Gap junction signaling between MDA-MB-231 cancer cells and astrocytes stimulates upregulation of interleukin 6 (IL-6) and IL-8 expression in cancer cells, which increases ET-1 production from astrocytes and ET receptor expression on cancer cells. ET-1 signals for activation of AKT/MAPK and upregulation of survival proteins that protect cancer cells from taxol. Brain endothelial cell-mediated chemoprotection of cancer cells also involves endothelin signaling. Dual antagonism of ETAR and ETBR is required to abolish astrocyte- and endothelial cell-mediated chemoprotection. Conclusions Bidirectional signaling between astrocytes and cancer cells involves upregulation and activation of the endothelin axis, which protects cancer cells from cytotoxicity induced by chemotherapeutic drugs. PMID:25008093

  11. MMP-1/PAR-1 signal transduction axis and its prognostic impact in esophageal squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Hong-hua Peng

    2012-01-01

    Full Text Available The matrix metalloprotease-1 (MMP-1/protease-activated receptor-1 (PAR-1 signal transduction axis plays an important role in tumorigenesis. To explore the expression and prognostic value of MMP-1 and PAR-1 in esophageal squamous cell carcinoma (ESCC, we evaluated the expression of two proteins in resected specimens from 85 patients with ESCC by immunohistochemistry. Sixty-two (72.9% and 58 (68.2% tumors were MMP-1- and PAR-1-positive, respectively, while no significant staining was observed in normal esophageal squamous epithelium. MMP-1 and PAR-1 overexpression was significantly associated with tumor node metastasis (TNM stage and regional lymph node involvement. Patients with MMP-1- and PAR-1-positive tumors, respectively, had poorer disease-free survival (DFS than those with negative ESCC (P = 0.002 and 0.003, respectively. Univariate analysis showed a significant relationship between TNM stage [hazard ratio (HR = 2.836, 95% confidence interval (CI = 1.866-4.308], regional lymph node involvement (HR = 2.955, 95%CI = 1.713-5.068, MMP-1 expression (HR = 2.669, 95%CI = 1.229-6.127, and PAR-1 expression (HR = 1.762, 95%CI = 1.156-2.883 and DFS. Multivariate analysis including the above four parameters identified TNM stage (HR = 2.035, 95%CI = 1.167-3.681, MMP-1 expression (HR = 2.109, 95%CI = 1.293-3.279, and PAR-1 expression (HR = 1.967, 95%CI = 1.256-2.881 as independent and significant prognostic factors for DFS. Our data suggest for the first time that MMP-1 and PAR-1 were both overexpressed in ESCC and are novel predictors of poor patient prognosis after curative resection. The MMP-1/PAR-1 signal transduction axis might be a new therapeutic target for future therapies tailored against ESCC.

  12. Active optics: off axis aspherics generation for high contrast imaging

    Science.gov (United States)

    Hugot, E.; Laslandes, M.; Ferrari, M.; Vives, S.; Moindrot, S.; El Hadi, K.; Dohlen, K.

    2017-11-01

    Active Optics methods, based on elasticity theory, allow the aspherisation of optical surfaces by stress polishing but also active aspherisation in situ. Researches in this field will impact the final performance and the final cost of any telescope or instrument. The stress polishing method is well suited for the superpolishing of aspheric components for astronomy. Its principle relies on spherical polishing with a full-sized tool of a warped substrate, which becomes aspherical once unwarped. The main advantage of this technique is the very high optical quality obtained either on form or on high spatial frequency errors. Furthermore, the roughness can be decreased down to a few angstroms, thanks the classical polishing with a large pitch tool, providing a substantial gain on the final scientific performance, for instance on the contrast on coronagraphic images, but also on the polishing time and cost. Stress polishing is based on elasticity theory, and requires an optimised deformation system able to provide the right aspherical form on the optical surface during polishing. The optical quality of the deformation is validated using extensive Finite Element Analysis, allowing an estimation of residuals and an optimisation of the warping harness. We describe here the work realised on stress polishing of toric mirrors for VLT-SPHERE and then our actual work on off axis aspherics (OAA) for the ASPIICS-Proba3 mission for solar coronagraphy. The ASPIICS optical design made by Vives et al is a three mirrors anastigmat including a concave off axis hyperboloid and a convex off axis parabola (OAP). We are developing a prototype in order to demonstrate the feasibility of this type of surface, using a multi-mode warping harness (Lemaitre et al). Furthermore, we present our work on variable OAP, meaning the possibility to adjust the shape of a simple OAP in situ with a minimal number of actuators, typically one actuator per optical mode (Focus, Coma and Astigmatism

  13. H I Kinematics along the Minor Axis of M82

    Science.gov (United States)

    Martini, Paul; Leroy, Adam K.; Mangum, Jeffrey G.; Bolatto, Alberto; Keating, Katie M.; Sandstrom, Karin; Walter, Fabian

    2018-03-01

    M82 is one of the best-studied starburst galaxies in the local universe, and is consequently a benchmark for studying star formation feedback at both low and high redshift. We present new VLA H I observations that reveal the cold gas kinematics along the minor axis in unprecedented detail. This includes the detection of H I up to 10 kpc along the minor axis toward the south and beyond 5 kpc to the north. A surprising aspect of these observations is that the line-of-sight H I velocity decreases substantially from about 120 to 50 {km} {{{s}}}-1 from 1.5 to 10 kpc off the midplane. The velocity profile is not consistent with the H I gas cooling from the hot wind. We demonstrate that the velocity decrease is substantially greater than the deceleration expected from gravitational forces alone. If the H I consists of a continuous population of cold clouds, some additional drag force must be present, and the magnitude of the drag force places a joint constraint on the ratio of the ambient medium to the typical cloud size and density. We also show that the H I kinematics are inconsistent with a simple conical outflow centered on the nucleus, but instead require the more widespread launch of the H I over the ∼1 kpc extent of the starburst region. Regardless of the launch mechanism for the H I gas, the observed velocity decrease along the minor axis is sufficiently great that the H I may not escape the halo of M82. The inferred H I outflow rate at 10 kpc off the midplane is much less than 1 {M}ȯ yr‑1.

  14. Endocannabinoid Signaling and the Hypothalamic-Pituitary-Adrenal Axis.

    Science.gov (United States)

    Hillard, Cecilia J; Beatka, Margaret; Sarvaideo, Jenna

    2016-12-06

    The elucidation of Δ9-tetrahydrocannabinol as the active principal of Cannabis sativa in 1963 initiated a fruitful half-century of scientific discovery, culminating in the identification of the endocannabinoid signaling system, a previously unknown neuromodulatory system. A primary function of the endocannabinoid signaling system is to maintain or recover homeostasis following psychological and physiological threats. We provide a brief introduction to the endocannabinoid signaling system and its role in synaptic plasticity. The majority of the article is devoted to a summary of current knowledge regarding the role of endocannabinoid signaling as both a regulator of endocrine responses to stress and as an effector of glucocorticoid and corticotrophin-releasing hormone signaling in the brain. We summarize data demonstrating that cannabinoid receptor 1 (CB1R) signaling can both inhibit and potentiate the activation of the hypothalamic-pituitary-adrenal axis by stress. We present a hypothesis that the inhibitory arm has high endocannabinoid tone and also serves to enhance recovery to baseline following stress, while the potentiating arm is not tonically active but can be activated by exogenous agonists. We discuss recent findings that corticotropin-releasing hormone in the amygdala enables hypothalamic-pituitary-adrenal axis activation via an increase in the catabolism of the endocannabinoid N-arachidonylethanolamine. We review data supporting the hypotheses that CB1R activation is required for many glucocorticoid effects, particularly feedback inhibition of hypothalamic-pituitary-adrenal axis activation, and that glucocorticoids mobilize the endocannabinoid 2-arachidonoylglycerol. These features of endocannabinoid signaling make it a tantalizing therapeutic target for treatment of stress-related disorders but to date, this promise is largely unrealized. © 2017 American Physiological Society. Compr Physiol 7:1-15, 2017. Copyright © 2017 John Wiley & Sons, Inc.

  15. Optical diffraction tomography: accuracy of an off-axis reconstruction

    Science.gov (United States)

    Kostencka, Julianna; Kozacki, Tomasz

    2014-05-01

    Optical diffraction tomography is an increasingly popular method that allows for reconstruction of three-dimensional refractive index distribution of semi-transparent samples using multiple measurements of an optical field transmitted through the sample for various illumination directions. The process of assembly of the angular measurements is usually performed with one of two methods: filtered backprojection (FBPJ) or filtered backpropagation (FBPP) tomographic reconstruction algorithm. The former approach, although conceptually very simple, provides an accurate reconstruction for the object regions located close to the plane of focus. However, since FBPJ ignores diffraction, its use for spatially extended structures is arguable. According to the theory of scattering, more precise restoration of a 3D structure shall be achieved with the FBPP algorithm, which unlike the former approach incorporates diffraction. It is believed that with this method one is allowed to obtain a high accuracy reconstruction in a large measurement volume exceeding depth of focus of an imaging system. However, some studies have suggested that a considerable improvement of the FBPP results can be achieved with prior propagation of the transmitted fields back to the centre of the object. This, supposedly, enables reduction of errors due to approximated diffraction formulas used in FBPP. In our view this finding casts doubt on quality of the FBPP reconstruction in the regions far from the rotation axis. The objective of this paper is to investigate limitation of the FBPP algorithm in terms of an off-axis reconstruction and compare its performance with the FBPJ approach. Moreover, in this work we propose some modifications to the FBPP algorithm that allow for more precise restoration of a sample structure in off-axis locations. The research is based on extensive numerical simulations supported with wave-propagation method.

  16. Gaussian tunneling model of c-axis twist Josephson junctions

    International Nuclear Information System (INIS)

    Bille, A.; Klemm, R.A.; Scharnberg, K.

    2001-01-01

    We calculate the critical current density J c J ((var p hi) 0 ) for Josephson tunneling between identical high-temperature superconductors twisted an angle (var p hi) 0 about the c axis. Regardless of the shape of the two-dimensional Fermi surface and for very general tunneling matrix elements, an order parameter (OP) with general d-wave symmetry leads to J c J (π/4)=0. This general result is inconsistent with the data of Li et al. [Phys. Rev. Lett. 83, 4160 (1999)] on Bi 2 Sr 2 CaCu 2 O 8+δ (Bi2212), which showed J c J to be independent of (var p hi) 0 . If the momentum parallel to the barrier is conserved in the tunneling process, J c J should vary substantially with the twist angle (var p hi) 0 when the tight-binding Fermi surface appropriate for Bi2212 is taken into account, even if the OP is completely isotropic. We quantify the degree of momentum nonconservation necessary to render J c J ((var p hi) 0 ) constant within experimental error for a variety of pair states by interpolating between the coherent and incoherent limits using five specific models to describe the momentum dependence of the tunneling matrix element squared. From the data of Li et al., we conclude that the c-axis tunneling in Bi2212 must be very nearly incoherent, and that the OP must have a nonvanishing Fermi-surface average for T c . We further show that the apparent conventional sum-rule violation observed by Basov et al. [Science 283, 49 (1999)] can be consistent with such strongly incoherent c-axis tunneling.

  17. Kynurenine pathway metabolism and the microbiota-gut-brain axis.

    Science.gov (United States)

    Kennedy, P J; Cryan, J F; Dinan, T G; Clarke, G

    2017-01-01

    It has become increasingly clear that the gut microbiota influences not only gastrointestinal physiology but also central nervous system (CNS) function by modulating signalling pathways of the microbiota-gut-brain axis. Understanding the neurobiological mechanisms underpinning the influence exerted by the gut microbiota on brain function and behaviour has become a key research priority. Microbial regulation of tryptophan metabolism has become a focal point in this regard, with dual emphasis on the regulation of serotonin synthesis and the control of kynurenine pathway metabolism. Here, we focus in detail on the latter pathway and begin by outlining the structural and functional dynamics of the gut microbiota and the signalling pathways of the brain-gut axis. We summarise preclinical and clinical investigations demonstrating that the gut microbiota influences CNS physiology, anxiety, depression, social behaviour, cognition and visceral pain. Pertinent studies are drawn from neurogastroenterology demonstrating the importance of tryptophan and its metabolites in CNS and gastrointestinal function. We outline how kynurenine pathway metabolism may be regulated by microbial control of neuroendocrine function and components of the immune system. Finally, preclinical evidence demonstrating direct and indirect mechanisms by which the gut microbiota can regulate tryptophan availability for kynurenine pathway metabolism, with downstream effects on CNS function, is reviewed. Targeting the gut microbiota represents a tractable target to modulate kynurenine pathway metabolism. Efforts to develop this approach will markedly increase our understanding of how the gut microbiota shapes brain and behaviour and provide new insights towards successful translation of microbiota-gut-brain axis research from bench to bedside. This article is part of the Special Issue entitled 'The Kynurenine Pathway in Health and Disease'. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Stress & the gut-brain axis: Regulation by the microbiome

    Directory of Open Access Journals (Sweden)

    Jane A. Foster

    2017-12-01

    Full Text Available The importance of the gut–brain axis in regulating stress-related responses has long been appreciated. More recently, the microbiota has emerged as a key player in the control of this axis, especially during conditions of stress provoked by real or perceived homeostatic challenge. Diet is one of the most important modifying factors of the microbiota-gut-brain axis. The routes of communication between the microbiota and brain are slowly being unravelled, and include the vagus nerve, gut hormone signaling, the immune system, tryptophan metabolism, and microbial metabolites such as short chain fatty acids. The importance of the early life gut microbiota in shaping later health outcomes also is emerging. Results from preclinical studies indicate that alterations of the early microbial composition by way of antibiotic exposure, lack of breastfeeding, birth by Caesarean section, infection, stress exposure, and other environmental influences - coupled with the influence of host genetics - can result in long-term modulation of stress-related physiology and behaviour. The gut microbiota has been implicated in a variety of stress-related conditions including anxiety, depression and irritable bowel syndrome, although this is largely based on animal studies or correlative analysis in patient populations. Additional research in humans is sorely needed to reveal the relative impact and causal contribution of the microbiome to stress-related disorders. In this regard, the concept of psychobiotics is being developed and refined to encompass methods of targeting the microbiota in order to positively impact mental health outcomes. At the 2016 Neurobiology of Stress Workshop in Newport Beach, CA, a group of experts presented the symposium “The Microbiome: Development, Stress, and Disease”. This report summarizes and builds upon some of the key concepts in that symposium within the context of how microbiota might influence the neurobiology of stress.

  19. Wake Development of a Model Vertical Axis Wind Turbine

    Science.gov (United States)

    Kadum, Hawwa; Friedman, Sasha; Camp, Elizabeth; Cal, Rau'l.

    2015-11-01

    At the Portland State University wind tunnel facility, an experiment is conducted to observe the downstream development of the wake past a model vertical axis wind turbine (VAWT). The flow domain is composed of streamwise-spanwise planes at mid-height of the VAWT rotor and data is obtained via particle image velocimetry (PIV). The flow field is assessed by analyzing contours of mean velocities and the full Reynolds stress tensor. Furthermore, profiles of the aforementioned quantities and flow parameters are discussed in the context of downstream evolution/flow development.

  20. Double tearing reconnection and the off-axis sawteeth crash

    International Nuclear Information System (INIS)

    Li Ding

    1998-01-01

    A theoretical model is developed for the onset of the off-axis sawteeth crash observed in TFTR reversed magnetic shear experiments. The dispersion relation of the double tearing mode is obtained from the solution structure of the ideal external kink equation. The onset of 'annular crash' is due to the fast reconnection of the hot and cold islands, triggered by the interaction of both branches of the double tearing mode. The onset of 'core crash' is mainly due to the coalescence between the hot islands, triggered by the explosive growth of the inner branch and the rapid expansion of the hot islands. (author)