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Search Results: 1 - 10 of 331075 matches for " Alan S. McNeilly "
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The In Utero Programming Effect of Increased Maternal Androgens and a Direct Fetal Intervention on Liver and Metabolic Function in Adult Sheep
Kirsten Hogg, Charlotte Wood, Alan S. McNeilly, W. Colin Duncan
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0024877
Abstract: Epigenetic changes in response to external stimuli are fast emerging as common underlying causes for the pre-disposition to adult disease. Prenatal androgenization is one such model that results in reproductive and metabolic features that are present in conditions such as polycystic ovary syndrome (PCOS). We examined the effect of prenatal androgens on liver function and metabolism of adult sheep. As non-alcoholic fatty liver disease is increased in PCOS we hypothesized that this, and other important liver pathways including metabolic function, insulin–like growth factor (IGF) and steroid receptivity, would be affected. Pregnant ewes received vehicle control (C; n = 5) or testosterone propionate (TP; n = 9) twice weekly (100 mg; i.m) from d62–102 (gestation 147 days). In a novel treatment paradigm, a second cohort received a direct C (n = 4) or TP (20 mg; n = 7) fetal injection at d62 and d82. In adults, maternal TP exposure resulted in increased insulin secretion to glucose load (P<0.05) and the histological presence of fatty liver (P<0.05) independent of central obesity. Additionally, hepatic androgen receptor (AR; P<0.05), glucocorticoid receptor (GR; P<0.05), UDP- glucose ceramide glucosyltransferase (UGCG; P<0.05) and IGF1 (P<0.01) expression were upregulated. The direct fetal intervention (C and TP) led to early fatty liver changes in all animals without differential changes in insulin secretion. Furthermore, hepatic phosphoenolpyruvate carboxykinase (PEPCK) was up-regulated in the fetal controls (P<0.05) and this was opposed by fetal TP (P<0.05). Hepatic estrogen receptor (ERα; P<0.05) and mitogen activated protein kinase kinase 4 (MAP2K4; P<0.05) were increased following fetal TP exposure. Adult liver metabolism and signaling can be altered by early exposure to sex steroids implicating epigenetic regulation of metabolic disturbances that are common in PCOS.
Endocrine Function in Aging
Huan Cai,Alan S. Mcneilly,Louis M. Luttrell,Bronwen Martin
International Journal of Endocrinology , 2012, DOI: 10.1155/2012/872478
Abstract:
Endocrine Function in Aging
Huan Cai,Alan S. Mcneilly,Louis M. Luttrell,Bronwen Martin
International Journal of Endocrinology , 2012, DOI: 10.1155/2012/872478
Abstract:
The Pancreas Is Altered by In Utero Androgen Exposure: Implications for Clinical Conditions Such as Polycystic Ovary Syndrome (PCOS)
Mick Rae, Cathal Grace, Kirsten Hogg, Lisa Marie Wilson, Sophie L. McHaffie, Seshadri Ramaswamy, Janis MacCallum, Fiona Connolly, Alan S. McNeilly, Colin Duncan
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0056263
Abstract: Using an ovine model of polycystic ovary syndrome (PCOS), (pregnant ewes injected with testosterone propionate (TP) (100 mg twice weekly) from day (d)62 to d102 of d147 gestation (maternal injection – MI-TP)), we previously reported female offspring with normal glucose tolerance but hyperinsulinemia. We therefore examined insulin signalling and pancreatic morphology in these offspring using quantitative (Q) RT-PCR and western blotting. In addition the fetal pancreatic responses to MI-TP, and androgenic and estrogenic contributions to such responses (direct fetal injection (FI) of TP (20 mg) or diethylstilbestrol (DES) (20 mg) at d62 and d82 gestation) were assessed at d90 gestation. Fetal plasma was assayed for insulin, testosterone and estradiol, pancreatic tissue was cultured, and expression of key β-cell developmental genes was assessed by QRT-PCR. In female d62MI-TP offspring insulin signalling was unaltered but there was a pancreatic phenotype with increased numbers of β-cells (P<0.05). The fetal pancreas expressed androgen receptors in islets and genes involved in β-cell development and function (PDX1, IGF1R, INSR and INS) were up-regulated in female fetuses after d62MI-TP treatment (P<0.05–0.01). In addition the d62MI-TP pancreas showed increased insulin secretion under euglycaemic conditions (P<0.05) in vitro. The same effects were not seen in the male fetal pancreas or when MI-TP was started at d30, before the male programming window. As d62MI-TP increased both fetal plasma testosterone (P<0.05) and estradiol concentrations (P<0.05) we assessed the relative contribution of androgens and estrogens. FI-TP (commencing d62) (not FI-DES treatment) caused elevated basal insulin secretion in vitro and the genes altered by d62MI-TP treatment were similarly altered by FI-TP but not FI-DES. In conclusion, androgen over-exposure alters fetal pancreatic development and β-cell numbers in offspring. These data suggest that that there may be a primary pancreatic phenotype in models of PCOS, and that there may be a distinct male and female pancreas.
Urinary gonadotrophins: a useful non-invasive marker of activation of the hypothalamic pituitary-gonadal axis
Jane D Mcneilly, Avril Mason, Sheila Khanna, Peter J Galloway, S. Faisal Ahmed
International Journal of Pediatric Endocrinology , 2012, DOI: 10.1186/1687-9856-2012-10
Abstract: 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).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 (p<0.001). In girls, FSH:Creatinine ratios were significantly higher in the pubertal group (p?=?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).Urinary gonadotrophins analyses could be used as non-invasive integrated measurement of pubertal status which reflects clinical/physical status.
Effects of Rotation on Turbulence Production  [PDF]
Alan S. Hsieh, Sedat Biringen
Journal of Applied Mathematics and Physics (JAMP) , 2019, DOI: 10.4236/jamp.2019.72024
Abstract: Direct numerical simulations (DNS) of non-rotating and rotating turbulent channel flow were conducted. The data base obtained from these DNS simulations was used to investigate the prominent coherent structures involved in the turbulence generation cycle. Predictions from three theoretical models concerning the formation and evolution of sublayer streaks, three-dimensional hairpin vortices and propagating plane waves were validated using visualizations from the present DNS data. Quadrant analysis was used to determine a phase shift between the fluctuating streamwise and wall-normal velocities as a characteristic of turbulence production in the suction region at a low rotation number.
Realizing the local Weil representation over a number field
Gerald Cliff,David McNeilly
Mathematics , 2009,
Abstract: We show that the Weil representation of the symplectic group Sp(2n,F), where F is a non-archimedian local field, can be realized over the field obtained from the rationals by adjoining the square roots of p and -p, where p is the residue characteristic of F; p is assumed to be odd.
Non-obstetric vaginal trauma  [PDF]
Ian S. C. Jones, Alan O’Connor
Open Journal of Obstetrics and Gynecology (OJOG) , 2013, DOI: 10.4236/ojog.2013.31005
Abstract:

Objective: To describe the mechanism, injury pattern and management of women who present to the Emergency Department with non-obstetric vaginal trauma. Methods: A retrospective, single institution case series was carried out. Data was sourced from medical records of women who presented to the Emergency Department and Royal Brisbane and Women’s Hospital between 2007 and 2011. Records of possible injuries to the vagina were assessed to determine incidence, age, site, type of injury, mechanism of injury and whether urinary retention required treatment. Results: Vaginal non-obstetric trauma was found in 11 of 519 cases resulting in lacerations or tears. Injuries were due to consensual coitus, other forms of sexual activity and self harm. Acute urinary retention did not occur in any case but two cases required resuscitation. Site of injury was most common high in the vagina. Conclusion: Non-obstetric vaginal injuries are uncommon (incidence 2.1%). All cases require assessment for vulvar, vaginal, urethral, anal and bony pelvis injuries. This may require examination under anaesthesia. Social worker and psychological support is important to reduce the incidence of long-term psychological problems.


A Dietary Supplement with a High Eicosapentaenoic Acid to Docosahexaenoic Acid Ratio Reduces Triglyceride Levels in Mildly Hypertriglyceridemic Subjects  [PDF]
Alan S. Ryan, Stephen S. Porter, Frederick D. Sancilio
Food and Nutrition Sciences (FNS) , 2013, DOI: 10.4236/fns.2013.41002
Abstract: There is compelling evidence that omega-3 long-chain polyunsaturated fatty acids (n-3 PUFA), eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) provide cardioprotective benefits. This open-label study evaluated whether an omega-3 fatty acid dietary supplement with a high EPA to DHA ratio (2.3:1) reduces triglyceride (TG) levels in mildly hypertriglyceridemic subjects. Twenty subjects, with a mean baseline TG level of 321.7 ± 108.7 mg/dL, were administered 4 g/day of Ocean Blue\"\"Professional Omega-3 2100TM (OB) supplements. Each gram of OB contains the ethyl esters of EPA (675 mg) and DHA (300 mg). Baseline and end of study blood values were collected to assess changes in fasting levels of TG, total cholesterol (TC), LDL-cholesterol (LDL-C), and HDL-cholesterol (HDL-C). Supplementation was provided for 30 to 228 days (mean = 106 ± 50 days). Mean age at enrollment was 50.3 ± 6.3 years. Compared with baseline values, mean TG levels decreased by 48% (p = 0.001). There were no changes in TC and HDL-C levels (p = NS); however, subjects had a significant increase in LDL-C levels (16.4%, p = 0.05). Results indicated that a high ratio of EPA to DHA (>2:1) had a statistically significant TG-lowering effect in mildly hypertriglyceridemic subjects. The lipid effects of OB are compared with those published in the literature for n-3 drugs indicated for hypertriglyceridemia (very high TG levels, > 500 mg/dL).
What is a virulence factor?
Alan S Cross
Critical Care , 2008, DOI: 10.1186/cc7127
Abstract: Infections are a leading cause of death in the intensive care unit. With the rising incidence of bacteria resistant to multiple antibiotics and a decreasing antibiotic drug pipeline, clinicians have sought additional therapies to supplement the current standard of care. Originally, such therapies, including anti-endotoxin antibodies and intravenous immunoglobulin, targeted the causative organisms. However, these efforts were supplanted by efforts to modulate the host responses to these organisms that were considered to be responsible for sepsis. Despite extensive clinical trials with biologic response modifiers, there is only one intervention licensed by the US Food and Drug Administration, drotrecogin alpha (Xigris?). Consequently, attention has now returned toward targeting the organisms. This development has been greatly assisted by the advent of genomics and systems biology, which have led to the identification of previously unrecognized targets on bacteria. These disciplines, in conjunction with advances in molecular biologic techniques, have led to striking advances in our understanding of the molecular pathogenesis of infection and the role of an ever-widening array of potential bacterial virulence factors. In their comprehensive review in this issue of Critical Care, Webb and Kahler [1] speculate that targeting virulence may be an attractive therapeutic strategy. Leaving aside the issues of drug formulation and/or delivery, what is required for the identification of a 'drugable' virulence target?Pathogens are perhaps the pre-eminent cell biologists, having over the span of millennia identified special niches or strategies, not only to subvert host defenses, but in some instances (like the polysialic acid K1 capsule of Escherichia coli) to elude detection through bacterial mimicry (by which the bacterial 'wolf' wraps itself in the 'sheep's clothing' of the host's cell). As these authors point out, many of the virulence mechanisms are now defined at precise mo
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