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Full-Text Articles in Medical Specialties

Cardiac Failure Following Inadvertent Administration Of High-Dose Epinephrine Subcutaneously, Kim A. Tran, Douglas D. Fraser, Krista Hawrylyshyn, Kambiz Norozi Jan 2012

Cardiac Failure Following Inadvertent Administration Of High-Dose Epinephrine Subcutaneously, Kim A. Tran, Douglas D. Fraser, Krista Hawrylyshyn, Kambiz Norozi

Paediatrics Publications

Our aim is to report the consequences of epinephrine toxicity leading to cardiac failure in a child and the successful management with dopamine and milrinone. A previously healthy 13-year-old girl undergoing a left tympanomastoidectomy was inadvertently administered 10 mL of 1:1000 epinephrine subcutaneously (0.175 mg/kg) on the left post auricular region in lieu of lidocaine. She developed sudden supraventricular tachycardia, hypertension and flash pulmonary edema. She was initially treated with propofol, nitrogycerin and increased peak end-expiratory pressure. Within 4 h, she remained tachycardic, but was hypotensive with an increased central venous pressure. Electrocardiogram and echocardiogram investigations showed ST changes indicative …


The Long And Short Of It: The Role Of Telomeres In Fetal Origins Of Adult Disease., Stephanie E Hallows, Timothy Regnault, Dean H Betts Jan 2012

The Long And Short Of It: The Role Of Telomeres In Fetal Origins Of Adult Disease., Stephanie E Hallows, Timothy Regnault, Dean H Betts

Paediatrics Publications

Placental insufficiency, maternal malnutrition, and other causes of intrauterine growth restriction (IUGR) can significantly affect short-term growth and long-term health. Following IUGR, there is an increased risk for cardiovascular disease and Type 2 Diabetes. The etiology of these diseases is beginning to be elucidated, and premature aging or cellular senescence through increased oxidative stress and DNA damage to telomeric ends may be initiators of these disease processes. This paper will explore the areas where telomere and telomerase biology can have significant effects on various tissues in the body in IUGR outcomes.


Master Transcription Factors Determine Cell-Type-Specific Responses To Tgf-Β Signaling, Alan C. Mullen, David A. Orlando, Jamie J. Newman, Jakob Lovén, Roshan M. Kumar, Steve Bilodeau, Jessica Reddy, Matthew G. Guenther, Rodney P. Dekoter, Richard A. Young Oct 2011

Master Transcription Factors Determine Cell-Type-Specific Responses To Tgf-Β Signaling, Alan C. Mullen, David A. Orlando, Jamie J. Newman, Jakob Lovén, Roshan M. Kumar, Steve Bilodeau, Jessica Reddy, Matthew G. Guenther, Rodney P. Dekoter, Richard A. Young

Paediatrics Publications

Transforming growth factor beta (TGF-β) signaling, mediated through the transcription factors Smad2 and Smad3 (Smad2/3), directs different responses in different cell types. Here we report that Smad3 co-occupies the genome with cell-type-specific master transcription factors. Thus, Smad3 occupies the genome with Oct4 in embryonic stem cells (ESCs), Myod1 in myotubes, and PU.1 in pro-B cells. We find that these master transcription factors are required for Smad3 occupancy and that TGF-β signaling largely affects the genes bound by the master transcription factors. Furthermore, we show that induction of Myod1 in nonmuscle cells is sufficient to redirect Smad3 to Myod1 sites. We …


The Effect Of Intermittent Umbilical Cord Occlusion On Elastin Composition In The Ovine Fetus., Jennifer A Thompson, Sarah A Gimbel, Bryan S Richardson, Robert Gagnon, Timothy Regnault Oct 2011

The Effect Of Intermittent Umbilical Cord Occlusion On Elastin Composition In The Ovine Fetus., Jennifer A Thompson, Sarah A Gimbel, Bryan S Richardson, Robert Gagnon, Timothy Regnault

Paediatrics Publications

This study aimed to determine the effect of varying degrees of intermittent umbilical cord occlusion (UCO) on arterial elastin composition. Over 4 days, chronically catheterized late gestation fetal sheep received 5 total UCO per day lasting 1 min/h (mild group: n = 6), 2 min/h (moderate group: n = 4), 3 min/h (severe group; n = 6); or no occlusion (control group: n = 7). Each group was evaluated for elastin content of the carotid and superior mesenteric artery (SMA), the arterial pressure response to UCO, and plasma cortisol concentration. Elastin content of the carotid artery was significantly increased by …


The Authors Reply:, Ajay P. Sharma, Guido Filler, Prabo Dwight, William F. Clark Jul 2011

The Authors Reply:, Ajay P. Sharma, Guido Filler, Prabo Dwight, William F. Clark

Paediatrics Publications

No abstract provided.


Integrin-Linked Kinase: A Scaffold Protein Unique Among Its Ilk, Lina Dagnino Jun 2011

Integrin-Linked Kinase: A Scaffold Protein Unique Among Its Ilk, Lina Dagnino

Paediatrics Publications

Integrin-linked kinase (ILK) is a scaffolding protein with central roles in tissue development and homeostasis. Much debate has focused on whether ILK is a bona fide or a pseudo- kinase. This aspect of ILK function has been complicated by the large volumes of conflicting observations obtained from a wide variety of experimental approaches, from in vitro models, to analyses in invertebrates and in mammals. Key findings in support or against the notion that ILK is catalytically active are summarized. The importance of ILK as an adaptor protein is well established, and defining its role as a signaling hub will be …


Rac1 Activation Induces Tumour Necrosis Factor-Α Expression And Cardiac Dysfunction In Endotoxemia, Ting Zhang, Xiangru Lu, Frank Beier, Qingping Feng May 2011

Rac1 Activation Induces Tumour Necrosis Factor-Α Expression And Cardiac Dysfunction In Endotoxemia, Ting Zhang, Xiangru Lu, Frank Beier, Qingping Feng

Paediatrics Publications

Induction of tumour necrosis factor-α (TNF-α) expression leads to myocardial depression during sepsis. However, the underlying molecular mechanisms are not fully understood. The aim of this study was to investigate the role of Rac1 in TNF-α expression and cardiac dysfunction during endotoxemia and to determine the involvement of phosphoinositide-3 kinase (PI3K) in lipopolysaccharide (LPS)-induced Rac1 activation. Our results showed that LPS-induced Rac1 activation and TNF-α expression in cultured neonatal mouse cardiomyocytes. The response was inhibited in Rac1 deficient cardiomyocytes or by a dominant-negative Rac1 (Rac1N17). To determine whether PI3K regulates Rac1 activation, cardiomyocytes were treated with LY294002, a PI3K selective …


Deletion Of Glycogen Synthase Kinase-3Β In Cartilage Results In Up-Regulation Of Glycogen Synthase Kinase-3Α Protein Expression, J. R. Gillespie, V. Ulici, H. Dupuis, A. Higgs, A. Dimattia, S. Patel, J. R. Woodgett, Frank Beier May 2011

Deletion Of Glycogen Synthase Kinase-3Β In Cartilage Results In Up-Regulation Of Glycogen Synthase Kinase-3Α Protein Expression, J. R. Gillespie, V. Ulici, H. Dupuis, A. Higgs, A. Dimattia, S. Patel, J. R. Woodgett, Frank Beier

Paediatrics Publications

The rate of endochondral bone growth determines final height in humans and is tightly controlled. Glycogen synthase kinase-3 (GSK-3) is a negative regulator of several signaling pathways that govern bone growth, such as insulin/IGF and Wnt/β-catenin. The two GSK-3 proteins, GSK-3 and GSK-3β, display both overlapping and distinct roles in different tissues. Here we show that pharmacological inhibition of GSK-3 signaling in a mouse tibia organ culture system results in enhanced bone growth, accompanied by increased proliferation of growth plate chondrocytes and faster turnover of hypertrophic cartilage to bone. GSK-3 inhibition rescues some, but not all, effects of phosphatidylinositide 3-kinase …


Maternal Protein Restriction Elevates Cholesterol In Adult Rat Offspring Due To Repressive Changes In Histone Modifications At The Cholesterol 7Α-Hydroxylase Promoter, Gurjeev Sohi, Kelly Marchand, Andrew Revesz, Edith Arany, Daniel B. Hardy May 2011

Maternal Protein Restriction Elevates Cholesterol In Adult Rat Offspring Due To Repressive Changes In Histone Modifications At The Cholesterol 7Α-Hydroxylase Promoter, Gurjeev Sohi, Kelly Marchand, Andrew Revesz, Edith Arany, Daniel B. Hardy

Paediatrics Publications

Adverse events in utero, such as intrauterine growth restriction (IUGR), can permanently alter epigenetic mechanisms leading to the metabolic syndrome, which encompasses a variety of symptoms including augmented cholesterol. The major site for cholesterol homeostasis occurs via the actions of hepatic cholesterol 7α-hydroxylase (Cyp7a1), which catabolizes cholesterol to bile acids. To determine whether posttranslational histone modifications influence the long-term expression of Cyp7a1 in IUGR, we used a protein restriction model in rats. This diet during pregnancy and lactation led to IUGR offspring with decreased liver to body weight ratios, followed by increased circulating and hepatic cholesterol levels in both sexes …


Human Spinal Cord Injury Causes Specific Increases In Surface Expression Of Beta Integrins On Leukocytes, Feng Bao, Christopher S. Bailey, Kevin R. Gurr, Stewart I. Bailey, M. Patricia Rosas-Arellano, Arthur Brown, Gregory A. Dekaban, Lynne C. Weaver Feb 2011

Human Spinal Cord Injury Causes Specific Increases In Surface Expression Of Beta Integrins On Leukocytes, Feng Bao, Christopher S. Bailey, Kevin R. Gurr, Stewart I. Bailey, M. Patricia Rosas-Arellano, Arthur Brown, Gregory A. Dekaban, Lynne C. Weaver

Paediatrics Publications

Spinal cord injury (SCI) activates circulating leukocytes that migrate into the injured cord and bystander organs using adhesion molecule-mediated mechanisms. These cells cause oxidative damage, resulting in secondary injury to the spinal cord, as well as injury to bystander organs. This study was designed to examine, over a 6-h to 2-week period, changes in adhesion molecule surface expression on human peripheral leukocytes after SCI (9 subjects), using as controls 10 uninjured subjects and 6 general trauma patients (trauma controls, TC). Both the percentage of cells expressing a given adhesion molecule and the average level of its expression was quantified for …


Hyperfiltration Affects Accuracy Of Creatinine Egfr Measurement, Shih Han S. Huang, Ajay P. Sharma, Abeer Yasin, Robert M. Lindsay, William F. Clark, Guido Filler Feb 2011

Hyperfiltration Affects Accuracy Of Creatinine Egfr Measurement, Shih Han S. Huang, Ajay P. Sharma, Abeer Yasin, Robert M. Lindsay, William F. Clark, Guido Filler

Paediatrics Publications

Background and objectives: Surrogate markers such as creatinine, cystatin C (CysC), and beta trace protein (BTP) have been used to estimate GFR (eGFR). The accuracy of eGFR may be altered with hyperfiltration and differences in filtration fraction (FF). It is hypothesized that the accuracy of creatinine for eGFR may be affected by hyperfiltration and different effective renal plasma flow (ERPF). Design, setting, participants, & measurements: A total of 127 pediatric patients with various renal diseases underwent simultaneous measurements of GFR using 51Cr-EDTA renal scan and ERPF ( 131I-hippurate clearance) to calculate the FF (FF = GFR/ERPF). The eGFRs were calculated …


Histamine Deficiency Promotes Inflammation-Associated Carcinogenesis Through Reduced Myeloid Maturation And Accumulation Of Cd11b +Ly6g+ Immature Myeloid Cells, Xiang Dong Yang, Walden Ai, Samuel Asfaha, Govind Bhagat, Richard A. Friedman, Guangchun Jin, Heuijoon Park, Benjamin Shykind, Thomas G. Diacovo, Andras Falus, Timothy C. Wang Jan 2011

Histamine Deficiency Promotes Inflammation-Associated Carcinogenesis Through Reduced Myeloid Maturation And Accumulation Of Cd11b +Ly6g+ Immature Myeloid Cells, Xiang Dong Yang, Walden Ai, Samuel Asfaha, Govind Bhagat, Richard A. Friedman, Guangchun Jin, Heuijoon Park, Benjamin Shykind, Thomas G. Diacovo, Andras Falus, Timothy C. Wang

Paediatrics Publications

Histidine decarboxylase (HDC), the unique enzyme responsible for histamine generation, is highly expressed in myeloid cells, but its function in these cells is poorly understood. Here we show that Hdc-knockout mice show a high rate of colon and skin carcinogenesis. Using Hdc-EGFP bacterial artificial chromosome (BAC) transgenic mice in which EGFP expression is controlled by the Hdc promoter, we show that Hdc is expressed primarily in CD11b +Ly6G+ immature myeloid cells (IMCs) that are recruited early on in chemical carcinogenesis. Transplant of Hdc-deficient bone marrow to wild-type recipients results in increased CD11b + Ly6G + cell mobilization and reproduces the …


Integrin-Linked Kinase Is Required For Tgf-_1 Induction Of Dermal Myofibroblast Differentiation, Linda Vi, Cristina De Lasa, Gianna M. Diguglielmo, Lina Dagnino Jan 2011

Integrin-Linked Kinase Is Required For Tgf-_1 Induction Of Dermal Myofibroblast Differentiation, Linda Vi, Cristina De Lasa, Gianna M. Diguglielmo, Lina Dagnino

Paediatrics Publications

Cutaneous repair after injury requires activation of resident dermal fibroblasts and their transition to myofibroblasts. The key stimuli for myofibroblast formation are activation of transforming growth factor-b (TGF-b) receptors and mechanotransduction mediated by integrins and associated proteins. We investigated the role of integrin-linked kinase (ILK) in TGF-b1 induction of dermal fibroblast transition to myofibroblasts. ILK-deficient fibroblasts treated with TGF-b1 exhibited attenuation of Smad 2 and 3 phosphorylation, accompanied by impaired transcriptional activation of Smad targets, such as a-smooth muscle actin. These alterations were not limited to Smad-associated TGF-b1 responses, as stimulation of noncanonical mitogenactivated protein kinase pathways by this growth …


Chest Compressions And Epinephrine During Resuscitation Of Infants Born At The Border Of Viability: Yes, No Or Maybe?, Gregory P. Moore, Thierry Daboval, Kevin W. Coughlin Jan 2011

Chest Compressions And Epinephrine During Resuscitation Of Infants Born At The Border Of Viability: Yes, No Or Maybe?, Gregory P. Moore, Thierry Daboval, Kevin W. Coughlin

Paediatrics Publications

Neonatology, in large part due to its population of babies born at the edge of viability, is rife with bioethical issues. This unique population is at high risk of mortality and considerable neurodevelopmental morbidity. One contentious, ongoing debate concerns whether these extremely low birth weight infants born at the border of viability should, if required by the Neonatal Resuscitation Program guidelines, receive chest compressions and epinephrine as part of their delivery room resuscitation. The present article, through a case presentation and discussion based on the ethical framework of principlism, provides readers with a thoughtful approach to the controversial issue of …


Epidemiology Of Pediatric Urolithiasis, Ajay P. Sharma, Guido Filler Oct 2010

Epidemiology Of Pediatric Urolithiasis, Ajay P. Sharma, Guido Filler

Paediatrics Publications

Pediatric urolithiasis has increased globally in the last few decades. There has been a change in the pattern of stone composition with an increase in the frequency of kidney stones and a decrease in bladder stones. The role of familial predisposition and environmental factors in pediatric urolithiasis is now better understood. Metabolic factors are more common in pediatric urolithiasis than in adult stone disease. This review updates on the epidemiology of pediatric urolithiasis with a focus on the changing trends in the stone disease, current spectrum of stone disease encountered in clinical practice, individual predisposition and the role of environmental …


Nox2 Deficiency Protects Against Streptozotocin-Induced Β-Cell Destruction And Development Of Diabetes In Mice, Fu Li Xiang, Xiangru Lu, Brenda Strutt, David J. Hill, Qingping Feng Oct 2010

Nox2 Deficiency Protects Against Streptozotocin-Induced Β-Cell Destruction And Development Of Diabetes In Mice, Fu Li Xiang, Xiangru Lu, Brenda Strutt, David J. Hill, Qingping Feng

Paediatrics Publications

OBJECTIVE - The role of NOX2-containing NADPH oxidase in the development of diabetes is not fully understood. We hypothesized that NOX2 deficiency decreases reactive oxygen species (ROS) production and immune response and protects against streptozotocin (STZ)-induced β-cell destruction and development of diabetes in mice. RESEARCH DESIGN AND METHODS - Five groups of mice-wild-type (WT), NOX2-/-, WT treated with apocynin, and WT adoptively transferred with NOX2-/- or WT splenocytes - were treated with multiple-low-dose STZ. Blood glucose and insulin levels were monitored, and an intraperitoneal glucose tolerance test was performed. Isolated WT and NOX2-/- pancreatic islets were treated with cytokines for …


Linking Brain-Wide Multivoxel Activation Patterns To Behaviour: Examples From Language And Math, Rajeev D.S. Raizada, Feng Ming Tsao, Huei Mei Liu, Ian D. Holloway, Daniel Ansari, Patricia K. Kuhl May 2010

Linking Brain-Wide Multivoxel Activation Patterns To Behaviour: Examples From Language And Math, Rajeev D.S. Raizada, Feng Ming Tsao, Huei Mei Liu, Ian D. Holloway, Daniel Ansari, Patricia K. Kuhl

Paediatrics Publications

A key goal of cognitive neuroscience is to find simple and direct connections between brain and behaviour. However, fMRI analysis typically involves choices between many possible options, with each choice potentially biasing any brain-behaviour correlations that emerge. Standard methods of fMRI analysis assess each voxel individually, but then face the problem of selection bias when combining those voxels into a region-of-interest, or ROI. Multivariate pattern-based fMRI analysis methods use classifiers to analyse multiple voxels together, but can also introduce selection bias via data-reduction steps as feature selection of voxels, pre-selecting activated regions, or principal components analysis. We show here that …


E-Mail Communication In Paediatrics: Ethical And Clinical Considerations, Susan Albersheim Mar 2010

E-Mail Communication In Paediatrics: Ethical And Clinical Considerations, Susan Albersheim

Paediatrics Publications

E-mail has become a commonplace ‘procedure’ in medical practice because it is efficient and inexpensive. However, there are potential misuses and abuses of this form of written communication, with clinical and ethical implications. Common uses of e-mail in paediatics include general communication with colleagues in a professional setting; electronic formal consultation, in which patient confidentiality is paramount; electronic ‘curbside’ consultation, which may be perceived as a formal consultation; electronic discussion groups, which lack peer review; communication with current patients or their parents, which should be limited to simple, nonurgent issues; and communication with individuals seeking medical advice who are not …


Nutrition And Exercise Prevent Excess Weight Gain In Overweight Pregnant Women, Michelle F. Mottola, Isabelle Giroux, Robert Gratton, Jo Anne Hammond, Anthony Hanley, Stewart Harris, Ruth Mcmanus, Margie H. Davenport, Maggie M. Sopper Feb 2010

Nutrition And Exercise Prevent Excess Weight Gain In Overweight Pregnant Women, Michelle F. Mottola, Isabelle Giroux, Robert Gratton, Jo Anne Hammond, Anthony Hanley, Stewart Harris, Ruth Mcmanus, Margie H. Davenport, Maggie M. Sopper

Paediatrics Publications

Purpose: To determine the effect of a Nutrition and Exercise Lifestyle Intervention Program (NELIP) for overweight (OW) and obese (OB) pregnant women on pregnancy weight gain, birth weight, and maternal weight retention at 2 months postpartum. Methods: This is a single-arm intervention matched by prepregnant body mass index, age, and parity to a historical cohort (4:1). Women with a prepregnancy body mass index of>25.0 kg•m (N = 65) participated in a NELIP starting at 16-20 wk of pregnancy, continuing until delivery. NELIP consisted of an individualized nutrition plan with total energy intake of approximately 2000 kcal•d (8360 kJ•d) and …


Chronic Renal Disease Is More Prevalent In Patients With Hemolytic Uremic Syndrome Who Had A Positive History Of Diarrhea, Ajay P. Sharma, Guido Filler, Prabo Dwight, William F. Clark Jan 2010

Chronic Renal Disease Is More Prevalent In Patients With Hemolytic Uremic Syndrome Who Had A Positive History Of Diarrhea, Ajay P. Sharma, Guido Filler, Prabo Dwight, William F. Clark

Paediatrics Publications

Many uncontrolled studies and a subsequent meta-analysis suggest that hemolytic uremic syndrome (HUS) with a positive history for diarrhea is associated with a significant increase in chronic renal disease. Two recent controlled studies that followed children with this type of HUS after Escherichia coli O157:H7 outbreaks, and where the controls were selected from a group exposed in the outbreak, gave conflicting results. To clarify this apparent difference, we retrospectively compared a cohort of 30 children with sporadic diarrhea-positive HUS with 30 healthy controls who had no history of bloody diarrhea or HUS and who had similar age and gender. Significantly …


Ppar_2 Expression In Growth Plate Chondrocytes Is Regulated By P38 And Gsk-3, Lee-Anne Stanton, Jennifer Ruizhe Li, Frank Beier Jan 2010

Ppar_2 Expression In Growth Plate Chondrocytes Is Regulated By P38 And Gsk-3, Lee-Anne Stanton, Jennifer Ruizhe Li, Frank Beier

Paediatrics Publications

Although peroxisome proliferator activated receptor (PPAR)_ remains a critical regulator of preadipocyte differentiation, new roles have been discovered in inflammation, bone morphogenesis, endothelial function, cancer, longevity and atherosclerosis. Despite the demonstration of PPAR expression in chondrocytes, its role and the pathways affecting its expression and activity in chondrocytes remain largely unknown. We investigated the effects of PPAR activation on chondrocyte differentiation and its participation in chondrocyte lipid metabolism. PPAR2 expression is highly regulated during chondrocyte differentiation in vivo and in vitro PPAR activation with troglitazone resulted in increased Indian hedgehog expression and reduced collagen X expression, confirming previously described roles …


Intrauterine Growth Restriction Increases Fetal Hepatic Gluconeogenic Capacity And Reduces Messenger Ribonucleic Acid Translation Initiation And Nutrient Sensing In Fetal Liver And Skeletal Muscle., Stephanie R Thorn, Timothy Regnault, Laura D Brown, Paul J Rozance, Jane Keng, Michael Roper, Randall B Wilkening, William W Hay, Jacob E Friedman Jul 2009

Intrauterine Growth Restriction Increases Fetal Hepatic Gluconeogenic Capacity And Reduces Messenger Ribonucleic Acid Translation Initiation And Nutrient Sensing In Fetal Liver And Skeletal Muscle., Stephanie R Thorn, Timothy Regnault, Laura D Brown, Paul J Rozance, Jane Keng, Michael Roper, Randall B Wilkening, William W Hay, Jacob E Friedman

Paediatrics Publications

Expression of key metabolic genes and proteins involved in mRNA translation, energy sensing, and glucose metabolism in liver and skeletal muscle were investigated in a late-gestation fetal sheep model of placental insufficiency intrauterine growth restriction (PI-IUGR). PI-IUGR fetuses weighed 55% less; had reduced oxygen, glucose, isoleucine, insulin, and IGF-I levels; and had 40% reduction in net branched chain amino acid uptake. In PI-IUGR skeletal muscle, levels of insulin receptor were increased 80%, whereas phosphoinositide-3 kinase (p85) and protein kinase B (AKT2) were reduced by 40%. Expression of eukaryotic initiation factor-4e was reduced 45% in liver, suggesting a unique mechanism limiting …


Effects Of Early Gestation Gh Administration On Placental And Fetal Development In Sheep., Casey D Wright, Ryan J Orbus, Timothy Regnault, Russell V Anthony Jul 2008

Effects Of Early Gestation Gh Administration On Placental And Fetal Development In Sheep., Casey D Wright, Ryan J Orbus, Timothy Regnault, Russell V Anthony

Paediatrics Publications

Ovine GH (oGH) is synthesized in placental tissue during maximal placental growth and development. Our objectives were to localize oGH mRNA in the placenta, and study the impact of exogenous GH on twin pregnancies during the normal window (35-55 days of gestational age; dGA) of placental expression. In situ hybridization localized oGH mRNA in uterine luminal epithelium but not in tissues of fetal origin. While maternal GH and IGF-I concentrations were increased (P


Chronic Late-Gestation Hypoglycemia Upregulates Hepatic Pepck Associated With Increased Pgc1alpha Mrna And Phosphorylated Creb In Fetal Sheep., Paul J Rozance, Sean W Limesand, James S Barry, Laura D Brown, Stephanie R Thorn, Dan Loturco, Timothy Regnault, Jacob E Friedman, William W Hay Feb 2008

Chronic Late-Gestation Hypoglycemia Upregulates Hepatic Pepck Associated With Increased Pgc1alpha Mrna And Phosphorylated Creb In Fetal Sheep., Paul J Rozance, Sean W Limesand, James S Barry, Laura D Brown, Stephanie R Thorn, Dan Loturco, Timothy Regnault, Jacob E Friedman, William W Hay

Paediatrics Publications

Hepatic glucose production is normally activated at birth but has been observed in response to experimental hypoglycemia in fetal sheep. The cellular basis for this process remains unknown. We determined the impact of 2 wk of fetal hypoglycemia during late gestation on enzymes responsible for hepatic gluconeogenesis, focusing on the insulin-signaling pathway, transcription factors, and coactivators that regulate gluconeogenesis. Hepatic phosphoenolpyruvate carboxykinase and glucose-6-phosphatase mRNA increased 12-fold and 7-fold, respectively, following chronic hypoglycemia with no change in hepatic glycogen. Chronic hypoglycemia decreased fetal plasma insulin with no change in glucagon but increased plasma cortisol 3.5-fold. Peroxisome proliferator-activated receptor-gamma coactivator-1alpha mRNA …


The Expression Of Ovine Placental Lactogen, Star And Progesterone-Associated Steroidogenic Enzymes In Placentae Of Overnourished Growing Adolescent Ewes., Richard G Lea, Peter Wooding, Ian Stewart, Lisa T Hannah, Stephen Morton, Karen Wallace, Raymond P Aitken, John S Milne, Timothy Regnault, Russell V Anthony, Jacqueline M Wallace Apr 2007

The Expression Of Ovine Placental Lactogen, Star And Progesterone-Associated Steroidogenic Enzymes In Placentae Of Overnourished Growing Adolescent Ewes., Richard G Lea, Peter Wooding, Ian Stewart, Lisa T Hannah, Stephen Morton, Karen Wallace, Raymond P Aitken, John S Milne, Timothy Regnault, Russell V Anthony, Jacqueline M Wallace

Paediatrics Publications

Overnourishing pregnant adolescent sheep promotes maternal growth but reduces placental mass, lamb birth weight and circulating progesterone. This study aimed to determine whether altered progesterone reflected transcript abundance for StAR (cholesterol transporter) and the steroidogenic enzymes (Cyp11A1, Hsd3b and Cyp17). Circulating and placental expression of ovine placental lactogen (oPL) was also investigated. Adolescent ewes with singleton pregnancies were fed high (H) or moderate (M) nutrient intake diets to restrict or support placental growth. Experiment 1: peripheral progesterone and oPL concentrations were measured in H (n=7) and M (n=6) animals across gestation (days 7-140). Experiment 2: progesterone was measured to mid- …


Altered Placental And Fetal Expression Of Igfs And Igf-Binding Proteins Associated With Intrauterine Growth Restriction In Fetal Sheep During Early And Mid-Pregnancy., Barbra De Vrijer, Meredith L Davidsen, Randall B Wilkening, Russell V Anthony, Timothy Regnault Nov 2006

Altered Placental And Fetal Expression Of Igfs And Igf-Binding Proteins Associated With Intrauterine Growth Restriction In Fetal Sheep During Early And Mid-Pregnancy., Barbra De Vrijer, Meredith L Davidsen, Randall B Wilkening, Russell V Anthony, Timothy Regnault

Paediatrics Publications

The insulin-like growth factors (IGFs) are postulated to be altered in association with the development of intrauterine growth restriction (IUGR). The present studies examined placental and fetal hepatic mRNA concentration of components of the IGF system at two time points (55 and 90 d gestational age, dGA; Term 147 dGA) in a hyperthermia (HT)-induced sheep model of placental insufficiency-IUGR. Maternal plasma insulin and IGF-I were constant at 55 and 90 dGA and were unaffected by treatment. Umbilical vein insulin concentrations tended to be reduced at 90 dGA following HT exposure. Caruncle IGF-I mRNA was increased at 90 dGA in HT …


Placental Expression Of Angiopoietin-1, Angiopoietin-2 And Tie-2 During Placental Development In An Ovine Model Of Placental Insufficiency-Fetal Growth Restriction., Amy S Erickson Hagen, Ryan J Orbus, Randall B Wilkening, Timothy Regnault, Russell V Anthony Dec 2005

Placental Expression Of Angiopoietin-1, Angiopoietin-2 And Tie-2 During Placental Development In An Ovine Model Of Placental Insufficiency-Fetal Growth Restriction., Amy S Erickson Hagen, Ryan J Orbus, Randall B Wilkening, Timothy Regnault, Russell V Anthony

Paediatrics Publications

Fetal growth restriction (FGR) is associated with increased perinatal morbidity and mortality, and often results from functional placental insufficiency. Placentation requires extensive vasculogenesis and subsequent angiogenesis, in both maternal and fetal tissues. Angiopoietin-1 (Ang-1) and Angiopoietin-2 (Ang-2) are angiogenic growth factors expressed in the placenta, and compete for binding to a common receptor, Tunica interna endothelial cell kinase-2 (Tie-2). Our objective was to examine Ang-1, Ang-2 and Tie-2 expression in ovine placental tissue obtained from normal and FGR pregnancies throughout gestation. Fetal cotyledon and maternal caruncle tissue concentrations of Ang-1, Ang-2 and Tie-2 mRNA were assessed by real-time reverse transcriptase-polymerase …


Investigating The Causes Of Low Birth Weight In Contrasting Ovine Paradigms., J M Wallace, Timothy Regnault, S W Limesand, W W Hay, R V Anthony May 2005

Investigating The Causes Of Low Birth Weight In Contrasting Ovine Paradigms., J M Wallace, Timothy Regnault, S W Limesand, W W Hay, R V Anthony

Paediatrics Publications

Intrauterine growth restriction (IUGR) still accounts for a large incidence of infant mortality and morbidity worldwide. Many of the circulatory and transport properties of the sheep placenta are similar to those of the human placenta and as such, the pregnant sheep offers an excellent model in which to study the development of IUGR. Two natural models of ovine IUGR are those of hyperthermic exposure during pregnancy, and adolescent overfeeding, also during pregnancy. Both models yield significantly reduced placental weights and an asymmetrically growth-restricted fetus, and display altered maternal hormone concentrations, indicative of an impaired trophoblast capacity. Additionally, impaired placental angiogenesis …