- Neonatal Respiratory Health Research
- Preterm Birth and Chorioamnionitis
- Birth, Development, and Health
- Congenital Diaphragmatic Hernia Studies
- Neuroscience of respiration and sleep
- Respiratory Support and Mechanisms
- Pregnancy and preeclampsia studies
- Infant Nutrition and Health
- Reproductive Physiology in Livestock
- Neonatal and fetal brain pathology
- Reproductive System and Pregnancy
- Cardiac Arrest and Resuscitation
- Immune Response and Inflammation
- Pregnancy-related medical research
- Fatty Acid Research and Health
- Reproductive tract infections research
- Renal and related cancers
- Pediatric Urology and Nephrology Studies
- Urological Disorders and Treatments
- Pregnancy and Medication Impact
- Glioma Diagnosis and Treatment
- Adipose Tissue and Metabolism
- Anesthesia and Neurotoxicity Research
- Pediatric health and respiratory diseases
- Pituitary Gland Disorders and Treatments
Monash University
2016-2025
Hudson Institute of Medical Research
2014-2025
Monash Health
2023
Hudson Institute
2013-2021
University of Minnesota
2018-2019
Cleveland Clinic
2015-2017
Indianapolis Zoo
2016
American College of Clinical Pharmacy
2016
University of North Carolina at Pembroke
2016
University of Otago
2016
REVIEW article Front. Neurosci., 21 May 2013Sec. Neuroendocrine Science Volume 7 - 2013 | https://doi.org/10.3389/fnins.2013.00079
Interleukin-1 (IL-1) is markedly overexpressed in Alzheimer's disease. We found the IL-1A 2,2 genotype 12.9% of 232 neuropathologically confirmed disease patients and 6.6% 167 controls from four centers United Kingdom States (odds ratio, 3.0; controlled for age ApoE [apolipoprotein E] genotype). Homozygosity both allele 2 IL-1B conferred even greater risk 10.8). IL-1 genotypes may confer through overexpression IL-1-driven neurodegenerative cascades.
Rationale: Premature infants are exposed to potentially injurious ventilation in the delivery room. Assessments of lung injury confounded by effects subsequent ventilatory support.Objectives: To evaluate response a brief period large tidal volume (Vt) ventilation, simulating neonatal resuscitation preterm neonates.Methods: Preterm lambs (129 d gestation; term is150 d) were ventilated (Vt = 15 ml/kg, no positive end-expiratory pressure) for minutes simulate room resuscitation, either with...
Intraamniotic endotoxin causes chorioamnionitis, which is followed by improved fetal lung function after 4 d in sheep. We evaluated 0.1 mg, 1 and 10 mg for inflammation maturation effects 7 d. Four caused similar the chorioamnion. The number of neutrophils cord blood inflammatory cells alveolar lavage tissue increased a dose-dependent manner. Lower doses induced indicators systemic without inducing maturation. Therefore, some degree can occur subsequent changes were assessed 5 h, 24 72 to...
Antenatal exposure to glucocorticoids, amnionitis, intraamniotic interleukin (IL)-1 α , or endotoxin can improve postnatal lung function after preterm delivery. The relationship between early maturation and the dose duration of a proinflammatory stimulus has not been evaluated. effects stimuli on fetal plasma cortisol also have We hypothesized that would induce in sheep without increasing cortisol. Intraamniotic injections 1, 4, 20, 100 mg Escherichia coli 055: β 5 caused 2-fold increases...
Our aim was to determine the postnatal effects of single and repeated glucocorticoid injections during late gestation. Repeated (104, 111, 118, 125 days) or (104 betamethasone saline were given ewe by ultrasound guided injection fetus (term 150 days). Lambs born spontaneously studied at 3 6 mo 1 yr age. Arterial pressure measured each age, we performed intravenous glucose tolerance tests yr. maternal, but not maternal fetal, prolonged gestation, reduced weight birth mo, associated with low...
Rationale: The technique used to provide continuous positive airway pressure (CPAP) the newborn may influence lung function and breathing efficiency.Objectives: To compare differences in gas exchange physiology injury resulting from treatment of respiratory distress with either bubble or constant CPAP determine if applied flow influences short-term outcomes.Methods: Lambs (133 d gestation; term is 150 d) born via cesarean section were weighed, intubated, treated for 3 hours. Two groups 8...
Experimental studies that are relevant to human pregnancy rely on the selection of appropriate animal models as an important element in experimental design. Consideration strengths and weaknesses any model disease is fundamental effective meaningful translation preclinical research. Studies sheep have made significant contributions our understanding normal abnormal development fetus. As a pregnancy, enabled scientists clinicians answer questions about etiology treatment poor maternal,...
Background and Purpose— White matter (WM) hyperintensities on MRI or leukoaraiosis is characteristic of stroke syndromes. Increased signals in the anterior temporal pole are suggested to be diagnostic for cerebral autosomal-dominant arteriopathy with subcortical infarcts leukoencephalopathy (CADASIL), 90% sensitivity 100% specificity. The structural correlates these specific WM seen T2-weighted FLAIR sequences CADASIL unclear. We assessed pathological changes postmortem tissue from reveal...
Megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS) is a rare disorder of enteric smooth muscle function affecting the intestine and bladder. Patients with this severe phenotype are dependent on total parenteral nutrition urinary catheterization. The cause has remained mystery since Berdon's initial description in 1976. No genes have been clearly linked to MMIHS. We used whole-exome sequencing for gene discovery followed by targeted Sanger cohort patients MMIHS intestinal...
We recently reported a deletion of exon 2 the trimethyllysine hydroxylase epsilon ( TMLHE ) gene in proband with autism. maps to X chromosome and encodes first enzyme carnitine biosynthesis, 6- N -trimethyllysine dioxygenase. Deletion causes deficiency, resulting increased substrate concentration (6- -trimethyllysine) decreased product levels (3-hydroxy-6- γ-butyrobetaine) plasma urine. deficiency is common control males (24 8,787 or 1 366) was not significantly frequency probands from...
Aims Preterm infants can be inadvertently exposed to high tidal volumes (VT) in the delivery room, causing lung inflammation and injury, but little is known about their effects on brain. The aim of this study was compare an initial 15 min VT resuscitation strategy a less injurious cerebral haemodynamics, injury. Methods lambs at 126 d gestation were surgically instrumented prior receiving with either: 1) High targeting 10–12 mL/kg for first (n = 6) or 2) protective (Prot VT), consisting...
The number of clinically relevant gene-based guidelines and recommendations pertaining to drug prescribing continues grow. Incorporating gene-drug interaction information into the drug-prescribing process can help optimize pharmacotherapy outcomes improve patient safety. However, pharmacogenomic implementation barriers exist such as integration results electronic health records (EHRs), development deployment decision support tools EHRs, feasible models for establishing ambulatory clinics. We...
Prenatal exposure to glucocorticoids is associated with alterations in fetal growth and endocrine function. However, few studies have examined the effects of clinically relevant doses on postnatal hypothalamic-pituitary-adrenal (HPA) To determine maternal or betamethasone administration (0.5 mg/kg estimated weight) HPA function at 6 months 1 year age, pregnant ewes were randomized into following treatment groups: no (n=6); saline single (M1) repeated (M4) (n=5); (n=6) (F4) (n=6). Single...
A contrast agent for use in magnetic resonance (MR) imaging of the liver and spleen has been designed which gadolinium-DTPA is chemically incorporated into lamellar phase liposome particles. This excellent vivo stability taken up by normal mice after intravenous administration. The T1 increased 110% 66% at 4 degrees C. At 37 degrees, relaxation rate 180%. method an attractive concept development various organ-specific liposomal agents that may be used either MR or nuclear medicine.
The preterm fetus is immune naive and has immature innate function. Although the frequently exposed to chorioamnionitis, effects of exposure fetal lung inflammation on responses are unknown. Using sheep model cord blood monocytes were isolated from lambs 1 14 days after intra-amniotic endotoxin injection, cultured for approximately 16 hours, challenged with in vitro. Compared adult sheep, produced less H(2)O(2) interleukin-6, toll-like receptor 4 expression was decreased. Three exposure,...
We determined the effects in preterm lambs of endotoxin-induced inflammation at early gestational ages on lung function and structure surfactant system. Pregnant ewes were randomized to one five intra-amniotic endotoxin (Escherichia coli 055:B5) groups: 1 mg injected 60 days gestation, 80 days, 100 plus or 0.6 mg/ day infused from Day 108. Control received saline treatments. At 125 was improved all groups. Marked increases saturated phosphatidylcholine tissue but not alveolar lavage samples...
Chorioamnionitis frequently associates with preterm delivery and increased amniotic fluid IL-1, causes fetal lung systemic inflammation. However, chorioamnionitis is also associated a paradoxical reduction in the incidence of surfactant deficiency-related respiratory distress syndrome infants.To identify role IL-1 signaling mediation pulmonary inflammation maturation sheep model lipopolysaccharide (LPS) induced chorioamnionitis.After confirming efficacy recombinant human receptor antagonist...