ORCID Profile
0000-0001-5568-9106
Current Organisation
University of South Australia
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Publisher: Cambridge University Press (CUP)
Date: 18-06-2018
DOI: 10.1017/S2040174418000260
Abstract: Perinatal exposure to sucrose or high-fructose corn syrup-55 (HFCS-55) in rats has previously been associated with altered hepatic fat content and composition post-weaning, although the effects on hepatic metabolism are unknown. The current study aimed to determine the sex-specific effects of maternal consumption of sucrose or HFCS-55 on the expression of hepatic lipogenic genes in the offspring. Liver s les were collected from offspring of albino Wistar rats provided with ad libitum access to either water (control), 10% sucrose or 10% HFCS-55 solution during pregnancy and lactation at 3 weeks (control n =16, sucrose n =22, HFCS-55 n =16) and 12 weeks (control n =16, sucrose n =10, HFCS-55 n =16) of age. Hepatic expression of the transcription factors such as carbohydrate response element-binding protein, sterol regulatory element-binding protein-1c and downstream genes was determined by quantitative real-time PCR. Sucrose-exposed offspring had higher hepatic SREBP-1c messenger RNA expression compared with control and HFCS-55 groups at both 3 weeks ( P =0.01) and 12 weeks ( P =0.03) of age. There were no differences in the expression of other hepatic lipogenic genes between groups at either 3 or 12 weeks. Thus, perinatal exposure to sucrose may be more detrimental to offspring hepatic metabolism compared with HFCS-55, independent of sex, and it will be important to evaluate the longer-term effects of perinatal sucrose exposure in future studies.
Publisher: Elsevier BV
Date: 2011
DOI: 10.1016/J.MCE.2010.10.018
Abstract: Expression of insulin-like growth factor (IGF)1 and IGF2 and their receptor (IGF1R and IGF2R) mRNA in fetal skeletal muscle are changed by variations in maternal nutrient intake. The persistence of these effects into postnatal life and their association with phenotype in beef cattle is unknown. Here we report that the cross-sectional areas of longissimus dorsi and semitendinosus (ST) muscles were greater for mature male progeny born to heifers fed low protein diets (70% vs. 240% of recommended) during the first trimester. In ST, this was accompanied by greater IGF1, IGF2 and IGF2R mRNA at 680 d. Females exposed to low protein diets during the first trimester had decreased IGF2 mRNA in ST at 680 d, however this did not result in an effect to phenotype. Exposure to low protein diets during the second trimester increased IGF1R mRNA in ST of all progeny at 680 d. Changes to expression of IGF genes in progeny skeletal muscle resulting from variations to maternal protein intake during gestation may have permanent and sex-specific effect on postnatal skeletal muscle growth.
Publisher: The Endocrine Society
Date: 04-2007
DOI: 10.1210/EN.2006-0761
Abstract: Periconceptional undernutrition (PCUN) results in an earlier prepartum activation of the pituitary-adrenal axis in twin compared with singleton fetuses. We have tested the hypotheses that the functional development of the fetal sheep adrenal is delayed in twins compared with singletons in early gestation and that PCUN accelerates adrenal growth and increases the expression of intraadrenal IGF-I and -II and cytochrome P450 17-hydroxylase (CYP17) as early as 55 d gestation. We have investigated the effect of PCUN in the ewe (restricted at 70% of control allowance, n=21 control, n=24) from at least 45 d before mating until d 7 after mating on maternal cortisol and progesterone concentrations, fetal adrenal weight, adrenal IGF-I, IGF-I receptor (IGF-IR), IGF-II, IGF-IIR, and CYP17 mRNA expression and placental 11beta-hydroxysteroid dehydrogenase-1 and -2 mRNA and protein expression at d 53-56 pregnancy. The relative weight of the fetal adrenal and adrenal IGF-I, IGF-IR, IGF-II, IGF-IIR, and CYP17 mRNA expression were lower in twin compared with singleton fetuses. In singleton fetuses of PCUN ewes, there was a loss of the relationship between adrenal IGF-II/IGF-IIR expression and either adrenal weight or CYP17 mRNA, which was present in controls. Similarly in twin fetuses, PCUN resulted in the loss of the relationships between adrenal weight and IGF-I expression and between adrenal CYP17 and IGF-II expression, which were present in controls. Our findings suggest that differences in the timing of the prepartum activation of the fetal adrenal in twins and singletons have their origins in early gestation and highlight the importance of the interaction between the periconceptional environment and embryo number in setting the growth trajectory of the fetal adrenal.
Publisher: Springer New York
Date: 05-10-2019
DOI: 10.1007/978-1-4939-9882-1_3
Abstract: In order to better understand the events that precede and precipitate the onset of type 2 diabetes (T2DM), several nutritional animal models have been developed. These models are generated by manipulating the diet of either the animal itself, or its mother during her pregnancy, and in comparison to traditional genetic and knock out models, have the advantage that they more accurately reflect the etiology of human T2DM. This chapter will discuss some of the most widely used nutritional models of T2DM: Diet-induced obesity (DIO) in adult rodents, and studies of offspring of mothers fed a low-protein, high-fat and/or high-sugar diet during pregnancy and/or lactation. Several common mechanisms have been identified through which these nutritional manipulations can lead to metabolic disease, including pancreatic beta-cell dysfunction, impaired insulin signaling in skeletal muscle, and the excess accumulation of visceral adipose tissue and consequent deposition of nonesterified fatty acids in peripheral tissues. In addition, there is an emerging concept that obesity oor quality diets result in increased production and release of pro-inflammatory cytokines from adipose tissue leading to a state of chronic low-grade inflammation, and that this is likely to represent an important link between obesity/diet and metabolic dysfunction. The following chapter will discuss the most common nutritional models of T2DM in experimental animals, their application, and relationship to human etiology, and will highlight the important insights these models have provided into the pathogenesis of T2DM.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2006
Publisher: Wiley
Date: 27-10-2013
Abstract: Fructose is an increasingly common constituent of the Westernized diet due to cost and production efficiencies. Although an integral component of our pre-industrial revolution diet, over the past two decades human and animal studies have highlighted that excessive fructose intake appears to be associated with adverse metabolic effects. Excessive intake of fructose is the combined result of increased total energy consumption and increased portion sizes of foods, which often incorporate the fructose-containing sugars sucrose and high-fructose corn-syrup (HFCS). The adverse metabolic effects following excessive fructose consumption have become a hot topic in mainstream media and there is now rigorous scientific debate regarding periods of exposure, dosage levels, interactive effects with other sugars and fats and mechanisms underlying the actions of fructose. There is still a degree of controversy regarding the extent to which sugars such as sucrose and HFCS have contributed to the current epidemic of obesity and diabetes. Furthermore, an increasing number of infants are being exposed to sugar-sweetened food and beverages before birth and during early postnatal life, highlighting the importance of determining the long-term effects of this perinatal exposure on the developing offspring. There are limited human observational and controlled studies identifying associations of excessive sweetened food and beverage consumption with poor pregnancy outcomes. Animal research has demonstrated an increased incidence of gestational diabetes as well as altered maternal, fetal and offspring metabolic function, although the long-term effects and the mechanism underlying these perturbations are ill defined. This review aims to understand the role of early life fructose exposure in modifying postnatal risk of disease in the offspring, focusing on fructose intake during pregnancy and in early postnatal life.
Publisher: Oxford University Press (OUP)
Date: 10-07-2017
DOI: 10.1093/JAC/DKX209
Abstract: To determine the existence of concentration-toxicity relationships for common β-lactam antibiotic adverse effects and define thresholds above which toxicity is more likely. Retrospective review of consecutive patients treated with piperacillin, meropenem or flucloxacillin who underwent therapeutic drug monitoring (TDM) at St Vincent's Hospital (Sydney, Australia) between January 2013 and December 2015. Adverse events investigated included neurotoxicity, nephrotoxicity, hepatotoxicity and opportunistic Clostridium difficile infection. Toxicity was measured using observational grading criteria, clinical assessment and relevant serum biomarkers. These findings were correlated with trough TDM measurements at the time of toxicity presentation. TDM results from 378 patients (piperacillin = 223, meropenem = 94 and flucloxacillin = 61) were investigated. There was no difference in baseline patient characteristics across antibiotic groups. A statistically significant elevation in mean serum trough concentrations (Cmin) was found in patients diagnosed with neurotoxicity (piperacillin, P < 0.01 meropenem, P = 0.04 flucloxacillin, P = 0.01) and those who developed nephrotoxicity whilst being treated with piperacillin (P < 0.01) or meropenem (P 361.4 mg/L meropenem, Cmin >64.2 mg/L flucloxacillin, Cmin >125.1 mg/L) or nephrotoxicity (piperacillin, Cmin >452.65 mg/L meropenem, Cmin >44.45 mg/L) varied across antibiotics. Our data reveal an association between toxic concentrations for a number of β-lactam agents and neurotoxic/nephrotoxic effects. We have defined threshold concentrations above which these toxicities become more likely. Clinicians should balance concerns for therapeutic efficacy with potential toxicity when considering aggressive therapy.
Publisher: MDPI AG
Date: 20-09-2016
DOI: 10.3390/NU8090577
Publisher: Elsevier BV
Date: 2020
DOI: 10.1016/J.THERIOGENOLOGY.2019.09.001
Abstract: This study reports the distribution of sperm morphology defects by breed, age, season and region of 11,387 bulls in 500 herds in Australia and near Pacific Islands during annual BBSE. Bull location was ided into 4 broad climatic regions based upon temperature, vegetation and climatic risk. Taking into account the impact of age, season, region, and breed there were differences between breeds in both percent morphologically normal sperm and in some in idual categories of sperm abnormality (P < 0.001). Independent of breed, season and region, proximal droplets were significantly increased in bulls less than 20 months of age. This is the first study to comprehensively collect data from this wide geographical area and compare sperm morphology profiles among the Bos indicus and Bos taurus breeds. The findings of this study will act as a guide for veterinary practitioners and cattle breeders in the proportion of bulls that can be expected to pass the PNS test, by breed, age and region, based on a robust data set.
Publisher: Springer Science and Business Media LLC
Date: 22-12-2010
DOI: 10.1007/S00467-009-1407-3
Abstract: There is an association between growing slowly before birth, accelerated growth in early postnatal life and the emergence of insulin resistance, visceral obesity and glucose intolerance in adult life. In this review we consider the pathway through which intrauterine growth restriction (IUGR) leads to the initial increase in insulin sensitivity and to catch-up growth. We also discuss the importance of the early insulin environment in determining later visceral adiposity and the intrahepatic mechanisms that may result in the emergence of glucose intolerance in a subset of IUGR infants. We present evidence that a key fetal adaptation to poor fetal nutrition is an upregulation of the abundance of the insulin receptor in the absence of an upregulation of insulin signalling in fetal skeletal muscle. After birth, however, there is an upregulation in the abundance of the insulin receptor and the insulin signalling pathway in the IUGR offspring. Thus, the origins of the accelerated postnatal growth rate experienced by IUGR infants lie in the fetal adaptations to a poor nutrient supply. We also discuss how the intracellular availability of free fatty acids and glucose within the visceral adipocyte and hepatocyte in fetal and neonatal life are critical in determining the subsequent metabolic phenotype of the IUGR offspring. It is clear that a better understanding of the relative contributions of the fetal and neonatal nutrient environment to the regulation of key insulin signalling pathways in muscle, visceral adipose tissue and the liver is required to support the development of evidence-based intervention strategies and better outcomes for the IUGR infant.
Publisher: Springer Science and Business Media LLC
Date: 17-08-2018
DOI: 10.1007/S10096-018-3357-9
Abstract: To determine whether target concentration non-attainment can be anticipated in critically ill patients prior to initiating empiric β-lactam antibiotic therapy based on readily available clinical factors. Retrospective review of consecutive patients treated with piperacillin or meropenem and who underwent therapeutic drug monitoring (TDM) at St Vincent's Hospital (Sydney, Australia) between January 2013 and December 2015 was performed. Predefined subgroups were patients who received continuous renal replacement therapy (CRRT) and those who did not (non-CRRT). Potential risk factors were evaluated by correlation with β-lactam antibiotic trough concentrations (C
Publisher: Cambridge University Press (CUP)
Date: 10-12-2015
DOI: 10.1017/S2040174415007965
Abstract: Clinical studies have reported beneficial effects of a maternal low glycaemic index (GI) diet on pregnancy and neonatal outcomes, but the impact of the diet on the offspring in later life, and the mechanisms underlying these effects, remain unclear. In this study, Albino Wistar rats were fed either a low GI ( n= 14) or high GI ( n= 14) diet during pregnancy and lactation and their offspring weaned onto either the low or high GI diet. Low GI dams had better glucose tolerance (AUC [glucose], 1322±55 v. 1523±72 mmol min/l, P .05) and a lower proportion of visceral fat (19.0±2.9 v. 21.7±3.8% of total body fat, P .05) compared to high GI dams. Female offspring of low GI dams had lower visceral adiposity (0.45±0.03 v. 0.53±0.03% body weight, P .05) and higher glucose tolerance (AUC [glucose] , 1243±29 v. 1351±39 mmol min/l, P .05) at weaning, as well as lower hepatic PI3K-p85 mRNA at 12 weeks of age. No differences in glucose tolerance or hepatic gene expression were observed in male offspring, but the male low GI offspring did have reduced hepatic lipid content at weaning. These findings suggest that consuming a low GI diet during pregnancy and lactation can improve glucose tolerance and reduce visceral adiposity in the female offspring at weaning, and may potentially produce long-term reductions in the hepatic lipogenic capacity of these offspring.
Publisher: Wiley
Date: 26-05-2017
DOI: 10.1113/JP274066
Publisher: American Physiological Society
Date: 04-2006
DOI: 10.1152/AJPREGU.00573.2005
Abstract: It is unknown whether the JAK/STAT/suppressor of cytokine signaling-3 (SOCS-3) intracellular signaling pathway plays a role in tissue growth and metabolism during fetal life. We investigated whether there is a differential profile of SOCS-3 expression in the liver and perirenal adipose tissue during the period of increased fetal growth in late gestation and the impact of fetal growth restriction on SOCS-3 expression in the fetal liver. We also determined whether basal SOCS-3 expression in the fetal liver and perirenal adipose tissue is regulated by endogenous fetal prolactin (PRL). SOCS-3 mRNA abundance was higher in the liver than in the pancreas, spleen, and kidney of the sheep fetus during late gestation. In the liver, SOCS-3 mRNA expression was increased ( P 0.05) between 125 ( n = 4) and 145 days ( n = 7) gestation and lower ( P 0.05) in growth-restricted compared with normally grown fetal sheep in late gestation. The relative expression of SOCS-3 mRNA in the fetal liver was directly related to the mean plasma PRL concentrations during a 48-h infusion of either a dopaminergic agonist, bromocriptine ( n = 7), or saline ( n = 5), such that SOCS-3 mRNA expression was lower when plasma PRL concentrations decreased below ∼20 ng/ml [ y = 0.99 − (2.47/ x) + (4.96/ x 2 ) r 2 = 0.91, P 0.0001, n = 12]. No relationship was shown between the abundance of phospho-STAT5 in the fetal liver and circulating PRL. SOCS-3 expression in perirenal adipose tissue decreased ( P 0001) between 90–91 ( n = 6) and 140–145 days ( n = 9) gestation and was not related to endogenous PRL concentrations. Thus SOCS-3 is differentially expressed and regulated in key fetal tissues and may play an important and tissue-specific role in the regulation of cellular proliferation and differentiation before birth.
Publisher: Bioscientifica
Date: 2007
DOI: 10.1677/JOE.1.06801
Abstract: The liver is a major metabolic and endocrine organ of critical importance in the regulation of growth and metabolism. Its function is determined by a complex interaction of nutritionally regulated counter-regulatory hormones. The extent to which hepatic endocrine sensitivity can be programed in utero and whether the resultant adaptations persist into adulthood is unknown and was therefore the subject of this study. Young adult male sheep born to mothers that were fed either a control diet (i.e.100% of total live weight-maintenance requirements) throughout gestation or 50% of that intake (i.e. nutrient restricted (NR)) from 0 to 95 days gestation and thereafter 100% of requirements (taking into account increasing fetal mass) were entered into the study. All mothers gave birth normally at term, the singleton offspring were weaned at 16 weeks, and then reared at pasture until 3 years of age when their livers were s led. NR offspring were of similar birth and body weights at 3 years of age when they had disproportionately smaller livers than controls. The abundance of mRNA for GH, prolactin, and IGF-II receptors, plus hepatocyte growth factor and suppressor of cytokine signaling-3 were all lower in livers of NR offspring. In contrast, the abundance of the mitochondrial protein voltage-dependent anion channel and the pro-apoptotic factor Bax were up regulated relative to controls. In conclusion, maternal nutrient restriction in early gestation results in adult offspring with smaller livers. This may be mediated by alterations in both hepatic mitogenic and apoptotic factors.
Publisher: Bioscientifica
Date: 05-2011
DOI: 10.1530/REP-10-0332
Abstract: Changes in maternal nutrient intake during gestation alter IGF receptor abundance and leptin ( LEP ) mRNA expression in fetal adipose tissue. It is not known whether such changes persist into adult life and whether they are associated with an effect on phenotype. We investigated the effect of high (240%) and low (70%) levels of recommended daily crude protein intake for beef heifers during the first and second trimesters of gestation on singleton progeny ( n =68): subcutaneous (SC) adipose tissue depth at rump (P8) and rib (RF) sites from 65 until 657 days of age plasma leptin concentrations from birth until 657 days and expression of IGF1 and IGF2 , their receptors ( IGF1R and IGF2R ) and LEP mRNA in perirenal (PR), omental (OM) and SC adipose tissue at 680 days of age. High-protein diets during the first trimester increased LEP and IGF1 mRNA in PR of males and females, respectively, compared with low-protein diets, and decreased IGF1R mRNA in SC of all progeny but increased RF depth of males between 552 and 657 days. High-protein diets compared with low-protein diets during the second trimester increased IGF1R mRNA in PR and OM of all progeny LEP mRNA in PR of males and IGF2 and IGF2R mRNA in OM of all progeny. Conversely, LEP mRNA in OM and IGF2 mRNA in PR of all progeny were decreased following exposure to high- compared with low-protein diets during the second trimester. Heifer diet during gestation has permanent sex- and depot-specific effects on the expression of adipogenic and adipocytokine genes and offspring adiposity.
Publisher: Elsevier BV
Date: 04-2019
Publisher: Springer Netherlands
Date: 2009
DOI: 10.1007/978-1-4020-9173-5_8
Abstract: Excess bodyweight is the sixth most important risk factor contributing to the overall burden of disease worldwide. In excess of a billion adults and 10% of all children are now classified as overweight or obese. The main adverse consequences of obesity are the metabolic syndrome, cardiovascular disease and type 2 diabetes and a diminished average life expectancy. It has been argued that the complex pathological processes underlying obesity reflect environmental and genetic interactions, and in iduals from disadvantaged communities seem to have greater risks than more affluent in iduals partly because of fetal and postnatal programming interactions. Abundant evidence indicates that the obesity epidemic reflects progressive secular and age-related decreases in physical activity, together with passive over-consumption of energy dense foods despite neurobiological processes designed to regulate energy balance. The difficulty in treating obesity, however, highlights the deficits in our current understanding of the pathophysiology which underlies the initiation and chronic nature of this disorder. Large population based studies in Europe and North America in healthy women and in women with gestational diabetes have demonstrated that there are clear relationships between maternal and fetal nutrient supply, fetal growth patterns and the subsequent risk of obesity and glucose intolerance in childhood and adult life. In this review we discuss the impact of fetal nutrition on the biology of the developing adipocyte and brain and the growing evidence base supporting an intergenerational cycle of obesity.
Publisher: Australasian Society for Computers in Learning in Tertiary Education
Date: 23-12-2020
DOI: 10.14742/AJET.6370
Abstract: Although technological advances have brought about new opportunities for scaling feedback to students, there remain challenges in how such feedback is presented and interpreted. There is a need to better understand how students make sense of such feedback to adapt self-regulated learning processes. This study examined students’ sense-making of learning analytics–based personalised feedback across four courses. Results from a combination of thematic analysis and epistemic network analysis show an association between student perceptions of their personalised feedback and how these map to subsequent self-described self-regulated learning processes. Most notably, the results indicate that personalised feedback, elaborated by personal messages from course instructors, helps students refine or strengthen important forethought processes of goal-setting, as well as to reduce procrastination. The results highlight the need for instructors to increase the dialogic element in personalised feedback in order to reduce defensive reactions from students who hold to their own learning strategies. This approach may prompt reflection on the suitability of students’ current learning strategies and achievement of associated learning goals. Implications for practice or policy: Personalised feedback based on learning analytics should be informed by an understanding of students’ self-regulated learning. Instructors implementing personalised feedback should align this closely with the course curriculum. Instructors implementing personalised feedback in their courses should consider the relational element of feedback by using a positive tone. Personalised feedback can be further enhanced by increasing the dialogic element and by including more information about learning strategies.
Publisher: Oxford University Press (OUP)
Date: 06-2009
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2018
DOI: 10.1097/DCR.0000000000001177
Abstract: Intraperitoneal local anesthetic is an analgesic technique for inclusion in the polypharmacy approach to postoperative pain management in enhanced recovery after surgery programs. Previously, augmentation of epidural analgesia with intraperitoneal local anesthetic was shown to improve functional postoperative recovery following colectomy. This study determines whether intraperitoneal local anesthetic improves postoperative recovery in patients undergoing colectomy, in the absence of epidural analgesia, with standardized enhanced recovery after surgery perioperative care. This is a multisite, double-blinded, randomized, placebo-controlled trial (ClinicalTrials.gov Identifier NCT02449720). This study was conducted at 3 hospital sites in South Australia. Eighty-six adults undergoing colectomy were stratified by approach (35 open 51 laparoscopic), then randomly assigned to intraperitoneal local anesthetic (n = 44) and control (n = 42) groups. Patients in the intraperitoneal local anesthetic group received an intraoperative intraperitoneal ropivacaine 100-mg bolus both pre- and postdissection and 20 mg/h continuous postoperative infusion for 48 hours. Patients in the control group received a normal saline equivalent. Functional postoperative recovery was assessed by using the surgical recovery scale for 45 days postoperative pain was assessed by using a visual analog scale and opioid consumption, use of rescue ketamine, recovery of bowel function, time to readiness for discharge, and perioperative complications were recorded. The intraperitoneal local anesthetic group reported improved surgical recovery scale scores at day 1 and 7, lower pain scores, required less rescue ketamine, and passed flatus earlier than the control group ( p 0.05). The improvement in surgical recovery scale at day 7 and pain scores remained when laparoscopic colectomy was considered separately. Opioid consumption and time to readiness for discharge were equivalent. This study was powered to detect a difference in surgical recovery scale, but not the other domains of recovery, when the intraperitoneal local anesthetic group was compared with control. We conclude that instillation and infusion of intraperitoneal ropivacaine for patients undergoing colectomy, including by the laparoscopic approach, decreases postoperative pain and improves functional postoperative recovery. We recommend routine inclusion of intraperitoneal local anesthetic into the multimodal analgesia component of enhanced recovery after surgery programs for laparoscopic colectomy. See Video Abstract at links.lww.com/DCR/A698.
Publisher: American Physiological Society
Date: 11-2006
DOI: 10.1152/AJPREGU.00252.2006
Abstract: The fetal pituitary-adrenal axis plays a key role in the fetal response to intrauterine stress and in the timing of parturition. The fetal sheep adrenal gland is relatively refractory to stimulation in midgestation (90–120 days) before the prepartum activation, which occurs around 135 days gestation (term = 147 ± 3 days). The mechanisms underlying the switch from adrenal quiescence to activation are unclear. Therefore, we have investigated the expression of suppressor of cytokine signaling-3 (SOCS-3), a putative inhibitor of tissue growth in the fetal sheep adrenal between 50 and 145 days gestation and in the adrenal of the growth-restricted fetal sheep in late gestation. SOCS-3 is activated by a range of cytokines, including prolactin (PRL), and we have, therefore, determined whether PRL administered in vivo or in vitro stimulates SOCS-3 mRNA expression in the fetal adrenal in late gestation. There was a decrease ( P 0.005) in SOCS-3 expression in the fetal adrenal between 54 and 133 days and between 141 and 144 days gestation. Infusion of the dopaminergic agonist, bromocriptine, which suppressed fetal PRL concentrations but did not decrease adrenal SOCS-3 mRNA expression. PRL administration, however, significantly increased adrenal SOCS-3 mRNA expression ( P 0.05). Similarly, there was an increase ( P 0.05) in SOCS-3 mRNA expression in adrenocortical cells in vitro after exposure to PRL (50 ng/ml). Placental and fetal growth restriction had no effect on SOCS-3 expression in the adrenal during late gestation. In summary, the decrease in the expression of the inhibitor SOCS-3 after 133 days gestation may be permissive for a subsequent increase in fetal adrenal growth before birth. We conclude that factors other than PRL act to maintain adrenal SOCS-3 mRNA expression before 133 days gestation but that acute elevations of PRL can act to upregulate adrenal SOCS-3 expression in the sheep fetus during late gestation.
Publisher: Springer International Publishing
Date: 2019
Publisher: Wiley
Date: 20-08-2019
DOI: 10.1002/MUS.26660
Abstract: This study assesses the burden, distribution, and evolution of muscle inflammation and damage on MRI among subtypes of idiopathic inflammatory myopathy (IIM). Musculoskeletal MRIs performed in 66 patients with IIM and 10 patients with non-IIM between 2009 and 2016 were retrospectively graded for muscle edema, fatty replacement (FR), and atrophy. Immune-mediated necrotizing myopathy (IMNM) patients had severe and extensive lower limb muscle edema, FR, and atrophy. The pelvic muscles and adductors were significantly more affected than in patients with dermatomyositis and polymyositis. Inclusion body myositis (IBM) was characterized by marked anterior thigh involvement, which stabilized or progressed at follow-up imaging. Atrophy and FR grades improved over time in some non-IBM IIM patients. Patients with IMNM and IBM have characteristic patterns of muscle MRI abnormalities that may allow them to be differentiated radiologically from other IIM subtypes. Muscle damage in non-IBM IIM may be reversible.
Publisher: Informa UK Limited
Date: 30-06-2021
Publisher: American Physiological Society
Date: 07-2011
DOI: 10.1152/JAPPLPHYSIOL.00067.2011
Abstract: The development of the adult cardiac troponin complex in conjunction with changes in cardiac function and cardiomyocyte binucleation has not been systematically characterized during fetal life in a species where maturation of the cardiomyocytes occurs prenatally as it does in the human. The aim of this study was to correlate the expression of each of the major adult troponin isoforms (T, I, and C) during late gestation (term of 150 days) to changes in both Ca 2+ sensitivity and maximum Ca 2+ -activated force of the contractile apparatus and the maturation of cardiomyocytes. The percentage of mononucleated cardiomyocytes in the right ventricle decreased with gestational age to 46% by 137–142 days of gestation. The length of binucleated cardiomyocytes did not change with gestational age, but the length of binucleated cardiomyocytes relative to heart weight decreased with gestational age. There was no change in the expression of adult cardiac troponin T with increasing gestation. The contractile apparatus was significantly more sensitive to Ca 2+ at 90 days compared with either 132 or 139 days of gestation, consistent with an ∼30% increase in the expression of adult cardiac troponin I between 90 and 110 days of gestation. Maximum Ca 2+ -activated force significantly increased from 90 days compared with 130 days consistent with an increase of ∼40% in cardiac troponin C protein expression. These data show that increased adult cardiac troponin I and C protein expression across late gestation is consistent with reduced Ca 2+ sensitivity and increased maximum Ca 2+ -activated force. Furthermore, changes in cardiac troponin C, not I, protein expression track with the timing of cardiomyocyte binucleation.
Publisher: Wiley
Date: 22-01-2008
DOI: 10.1111/J.1742-7843.2007.00188.X
Abstract: The 'developmental origins of adult health and disease' hypothesis stated that environmental factors, particularly maternal undernutrition, act in early life to programme the risks for adverse health outcomes, such as cardiovascular disease, obesity and the metabolic syndrome in adult life. Early physiological tradeoffs, including activation of the foetal hypothalamo-pituitary-adrenal (HPA) axis, confer an early fitness advantage such as foetal survival, while incurring delayed health costs. We review the evidence that such tradeoffs are anticipated from conception and that the periconceptional nutritional environment can programme the developmental trajectory of the stress axis and the systems that maintain and regulate arterial blood pressure. There is also evidence that restriction of placental growth and function, results in an increased dependence of the maintenance of arterial blood pressure on the sequential recruitment of the sympathetic nervous system and HPA axis. While the 'early origins of adult disease' hypothesis has focussed on the impact of maternal undernutrition, an increase in maternal nutritional intake and in maternal body mass intake has become more prevalent in developed countries. Exposure to overnutrition in foetal life results in a series of central and peripheral neuroendocrine responses that in turn programme development of the fat cell and of the central appetite regulatory system. While the physiological responses to foetal undernutrition result in the physiological trade off between foetal survival and poor health outcomes that emerge after reproductive senescence, exposure to early overnutrition results in poor health outcomes that emerge in childhood and adolescence. Thus, the effects of early overnutrition can directly impact on reproductive fitness and on the health of the next generation. In this context, the physiological responses to relative overnutrition in early life may directly contribute to an intergenerational cycle of obesity.
Publisher: Cambridge University Press (CUP)
Date: 19-12-2014
DOI: 10.1017/S2040174414000610
Abstract: Excess consumption of added sugars, including sucrose and high fructose corn syrup (HFCS-55), have been implicated in the global epidemics of obesity and type 2 diabetes. This study aimed to investigate and compare the impact of maternal consumption of sucrose or HFCS-55 during pregnancy and lactation on the metabolic health of the dam and her offspring at birth. Female Albino Wistar rats were given access to chow and water, in addition to a sucrose or HFCS-55 beverage (10% w/v) before, and during pregnancy and lactation. Maternal glucose tolerance was determined throughout the study, and a postmortem was conducted on dams following lactation, and on offspring within 24 h of birth. Sucrose and HFCS-55 consumption resulted in increased total energy intake compared with controls, however the increase from sucrose consumption was accompanied by a compensatory decrease in chow consumption. There was no effect of sucrose or HFCS-55 consumption on body weight, however sucrose consumption resulted in increased adiposity and elevated total plasma cholesterol in the dam, while HFCS-55 consumption resulted in increased plasma insulin and decreased plasma non-esterified fatty acids (NEFA). Maternal HFCS-55 consumption was associated with decreased relative liver weight and plasma NEFA in the offspring at birth. There was no effect of either treatment on pup weight at birth. These findings suggest that both sucrose and HFCS-55 consumption during pregnancy and lactation have the potential to impact negatively on maternal metabolic health, which may have adverse consequences for the long-term health of the offspring.
No related grants have been discovered for Sheridan Gentili.