In vivo Assessment of AMP2, a Novel Ceramic-Binding BMP-2, in Ovine Lumbar Interbody Fusion.

Study Design: Assessment of bone formation in an ovine interbody fusion study.

Objective: To compare OsteoAdapt SP, which consists of AMP-2, a modified variant of recombinant human bone morphogenetic protein (rhBMP-2) bound to a tricalcium phosphate-containing carrier, to autologous iliac crest bone graft (ICBG) in a lumbar interbody fusion model.

Summary Of Background Data: Treatment of lumbar disk degeneration often involves spinal fusion to reduce pain and motion at the affected spinal segment by insertion of a cage containing bone graft material.

Feasibility of a brief, in-patient coping and sleep intervention to reduce potentially preventable readmission of cardiac patients to hospital.

Background: Psychological distress is prevalent amongst hospital in-patient and may predispose patients to potentially preventable readmissions after discharge. A particularly vulnerable group are patients with cardiac disorders. This study tested the feasibility of a brief cognitive behavioural therapy consisting of an in-hospital coping session and a post-discharge healthy sleep session.

Hepatic cytochrome P450 function is reduced by life-long Western diet consumption in guinea pig independent of birth weight.

Introduction: Non-alcoholic fatty liver disease (NAFLD) is characterised by accumulation of triglycerides and cholesterol within the liver and dysregulation of specific hepatic cytochrome P450 (CYPs) activity. CYPs are involved in the metabolism of endogenous and exogenous chemicals. Hepatic CYP activity is dysregulated in human studies and animal models of a Western diet (WD) or low birth weight (LBW) independently, but the additive effects of LBW and postnatal WD consumption are unknown.

Intrauterine growth restriction alters the activity of drug metabolising enzymes in the maternal-placental-fetal unit.

Purpose: Ten percent of pregnancies are affected by intrauterine growth restriction (IUGR), and evidence suggests that affected neonates have reduced activity of hepatic cytochrome P450 (CYP) drug metabolising enzymes. Given that almost all pregnant individuals take medications and additional medications are often required during an IUGR pregnancy, we aimed to determine the impact of IUGR on hepatic CYP activity in sheep fetuses and pregnant ewes.

Methods: Specific probes were used to determine the impact of IUGR on the activity of several CYP isoenzymes (CYP1A2, CYP2C19, CYP2D6 and CYP3A) in sheep fetuses and pregnant ewes.

The reliance on α-adrenergic receptor stimuli for blood pressure regulation in the chronically hypoxaemic fetus is not dependent on post-ganglionic activation.

Key Points: Chronic hypoxaemia is associated with intrauterine growth restriction (IUGR) and a predisposition to the development of hypertension in adult life. IUGR fetuses exhibit a greater reliance on α-adrenergic activation for blood pressure regulation. The fetal blood pressure response to post-ganglionic blockade is not different between control and IUGR fetuses.

Development of a method to determine cytochrome P450 1A2, 2C9, 2D6 and 3A4 activity sheep hepatic microsomes.

Introduction: Ex vivo studies of human fetal hepatic drug metabolism are uncommon as it requires access to functional liver tissue and therefore raises practical and ethical concerns. Large animal models provide an alternative opportunity to study changes in cytochrome P450 (CYP) activity in the mother and fetus during pregnancy. We aimed to develop methods to determine the activity of CYP1A2, CYP2C9, CYP2D6 and CYP3A4 in sheep hepatic microsomes.

Simulated shift work during pregnancy does not impair progeny metabolic outcomes in sheep.

Key Points: Maternal shift work increases the risk of pregnancy complications, although its effects on progeny health after birth are not clear. We evaluated the impact of a simulated shift work protocol for one-third, two-thirds or all of pregnancy on the metabolic health of sheep progeny. Simulated shift work had no effect on growth, body size, body composition or glucose tolerance in pre-pubertal or young adult progeny.

The impact of intrauterine growth restriction on cytochrome P450 enzyme expression and activity.

With the increased prevalence of non-communicable disease and availability of medications to treat these and other conditions, a pregnancy free from prescribed medication exposure is rare. Up to 99% of women take at least one medication during pregnancy. These medications can be divided into those used to improve maternal health and wellbeing (e.

Cardiorespiratory consequences of intrauterine growth restriction: Influence of timing, severity and duration of hypoxaemia.

At birth, weight of the neonate is used as a marker of the 9-month journey as a fetus. Those neonates born less than the 10th centile for their gestational age are at risk of being intrauterine growth restricted. However, this depends on their genetic potential for growth and the intrauterine environment in which they grew.

Fetal cardiovascular response to acute hypoxia during maternal anesthesia.

Preclinical imaging studies of fetal hemodynamics require anesthesia to immobilize the animal. This may induce cardiovascular depression and confound measures under investigation. We compared the impact of four anesthetic regimes upon maternal and fetal blood gas and hemodynamics during baseline periods of normoxia, and in response to an acute hypoxic challenge in pregnant sheep.

Simulated shift work disrupts maternal circadian rhythms and metabolism, and increases gestation length in sheep.

Key Points: Shift work impairs metabolic health, although its effects during pregnancy are not well understood We evaluated the effects of a simulated shift work protocol for one-third, two-thirds or all of pregnancy on maternal and pregnancy outcomes in sheep. Simulated shift work changed the timing of activity, disrupted hormonal and cellular rhythms, and impaired maternal glucose tolerance during early pregnancy. Gestation length was increased in twin pregnancies, whereas singleton lambs were lighter at a given gestational age if mothers were subjected to shift work conditions in the first one-third of pregnancy.

Sleep disturbances in women with polycystic ovary syndrome: prevalence, pathophysiology, impact and management strategies.

Polycystic ovary syndrome (PCOS) is a complex endocrine disorder affecting the reproductive, metabolic and psychological health of women. Clinic-based studies indicate that sleep disturbances and disorders including obstructive sleep apnea and excessive daytime sleepiness occur more frequently among women with PCOS compared to comparison groups without the syndrome. Evidence from the few available population-based studies is supportive.

Maternal circadian rhythms and the programming of adult health and disease.

The in utero environment is inherently rhythmic, with the fetus subjected to circadian changes in temperature, substrates, and various maternal hormones. Meanwhile, the fetus is developing an endogenous circadian timing system, preparing for life in an external environment where light, food availability, and other environmental factors change predictably and repeatedly every 24 h. In humans, there are many situations that can disrupt circadian rhythms, including shift work, international travel, insomnias, and circadian rhythm disorders (e.

The impact of prenatal circadian rhythm disruption on pregnancy outcomes and long-term metabolic health of mice progeny.

Animal studies demonstrate that circadian rhythm disruption during pregnancy can be deleterious to reproductive capacity and the long-term health of the progeny. Our previous studies in rats have shown that exposure of pregnant dams to an environment that significantly disrupts maternal circadian rhythms programs increased adiposity and poor glucose metabolism in offspring. In this study, we used mice with a ClockΔ19 mutation to determine whether foetal development within a genetically disrupted circadian environment affects pregnancy outcomes and alters the metabolic health of offspring.

Fixed or Rotating Night Shift Work Undertaken by Women: Implications for Fertility and Miscarriage.

This review summarizes the evidence concerning effects of night shift work on women's reproductive health, specifically difficulty in conceiving and miscarriage. We distinguish between fixed night shift and rotating night shift, as the population subgroups exposed, the social and biological mechanisms, and the magnitude of effects are likely to differ; of note, women working fixed night shift are known to have high tolerance for this schedule. We identified two relevant systematic reviews with meta-analyses and five additional studies.

Research Priorities for Fertility and Conception Research as Identified by Multidisciplinary Health Care Practitioners and Researchers.

The Robinson Research Institute of the University of Adelaide convened a multidisciplinary group of n = 33 clinicians, researchers and representatives of government organisations on the 2 October 2014 for a workshop entitled "Promoting fertility and healthy conception. How do we generate greater reproductive health awareness?" The key aim of the workshop was to assess the body of knowledge that informs clinical practice and government policy, and to identify questions and additional information needed by health practitioners and government representatives working in the field of reproductive health and to frame future research and policy. The workshop identified topics that fell mostly into three categories: lifestyle-related, societal and biological factors.

Acute inhibition of casein kinase 1δ/ε rapidly delays peripheral clock gene rhythms.

Circadian rhythms are generated through a transcription-translation feedback loop involving clock genes and the casein kinases CSNK1D and CSNK1E. In this study, we investigated the effects of the casein kinase inhibitor PF-670462 (50 mg/kg) on rhythmic expression of clock genes in the liver, pancreas and suprachiasmatic nucleus (SCN) as well as plasma corticosterone, melatonin and running behaviour in rats and compared them to the responses to a 4 h extension of the light phase. PF-670462 acutely phase delayed the rhythmic transcription of Bmal1, Per1, Per2 and Nr1d1 in both liver and pancreas by 4.

Rapidly alternating photoperiods disrupt central and peripheral rhythmicity and decrease plasma glucose, but do not affect glucose tolerance or insulin secretion in sheep.

Disrupting circadian rhythms in rodents perturbs glucose metabolism and increases adiposity. To determine whether these effects occur in a large diurnal animal, we assessed the impact of circadian rhythm disruption upon metabolic function in sheep. Adult ewes (n = 7) underwent 3 weeks of a control 12 h light-12 h dark photoperiod, followed by 4 weeks of rapidly alternating photoperiods (RAPs) whereby the time of light exposure was reversed twice each week.

Metabolic consequences of timed feeding in mice.

The time of day at which meals are consumed is known to impact on behaviour as well as physiological systems. In this study we investigated the behavioural and physiological effects of restricting access to food to the light or dark period in mice maintained on either long or short photoperiods. In both photoperiods, wheel running commenced upon the onset of darkness and was generally confined to the period of darkness.

Global loss of bmal1 expression alters adipose tissue hormones, gene expression and glucose metabolism.

The close relationship between circadian rhythm disruption and poor metabolic status is becoming increasingly evident, but role of adipokines is poorly understood. Here we investigated adipocyte function and the metabolic status of mice with a global loss of the core clock gene Bmal1 fed either a normal or a high fat diet (22% by weight). Bmal1 null mice aged 2 months were killed across 24 hours and plasma adiponectin and leptin, and adipose tissue expression of Adipoq, Lep, Retn and Nampt mRNA measured.

Circadian regulation of reproduction: from gamete to offspring.

Few challenges are more critical to the survival of a species than reproduction. To ensure reproductive success, myriad aspects of physiology and behaviour need to be tightly orchestrated within the animal, as well as timed appropriately with the external environment. This is accomplished through an endogenous circadian timing system generated at the cellular level through a series of interlocked transcription/translation feedback loops, leading to the overt expression of circadian rhythms.

Characterisation of the maternal response to chronic phase shifts during gestation in the rat: implications for fetal metabolic programming.

Disrupting maternal circadian rhythms through exposure to chronic phase shifts of the photoperiod has lifelong consequences for the metabolic homeostasis of the fetus, such that offspring develop increased adiposity, hyperinsulinaemia and poor glucose and insulin tolerance. In an attempt to determine the mechanisms by which these poor metabolic outcomes arise, we investigated the impact of chronic phase shifts (CPS) on maternal and fetal hormonal, metabolic and circadian rhythms. We assessed weight gain and food consumption of dams exposed to either CPS or control lighting conditions throughout gestation.