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Share Cannabidiol Exposure During Gestation Leads To Adverse Cardiac Outcomes Early In Postnatal Life In Male Rat Offspring., Daniel B. Hardy, Steven R. Laviolette, Kendrick Lee, David Rc Natale

Physiology and Pharmacology Publications

Introduction: Studies indicate that *7% of pregnant individuals in North America consume cannabis in pregnancy. Pre-clinical studies have established that maternal exposure to D9-tetrahydrocannabinol (THC; major psychoactive component in cannabis) leads to fetal growth restriction and impaired cardiac function in offspring. However, the effects of maternal exposure to cannabidiol (CBD; major non-euphoric constituent) on cardiac outcomes in offspring remain unknown. Therefore, our objective is to investigate the functional and underlying molecular impacts in the hearts of offspring exposed to CBD in pregnancy. Methods: Pregnant Wistar rats were exposed to either 3 or 30mg/kg CBD or vehicle control i.p. daily from …

Cannabidiol Exposure During Rat Pregnancy Leads To Labyrinth-Specific Vascular Defects In The Placenta And Reduced Fetal Growth, Daniel B. Hardy, David R C Natale, Kendrick Lee

Physiology and Pharmacology Publications

Introduction: Cannabis use is increasing among pregnant people, and cannabidiol (CBD), a constituent of cannabis, is often perceived as ‘‘natural’’ and ‘‘safe’’ as it is non-intoxicating. In utero, cannabis exposure is associated with negative health outcomes, including fetal growth restriction (FGR). The placenta supplies oxygen and nutrients to the fetus, and alterations in placental development can lead to FGR. While there has been some investigation into the effects of D9-THC, there has been limited investigation into the impacts of in utero gestational CBD exposure on the placenta. Methods: This study used histological and transcriptomic analysis of embryonic day (E)19.5 rat …

Critically Ill Covid-19 Patients Exhibit Anti-Sars-Cov-2 Serological Responses, Mark Daley, Douglas D. Fraser, Gediminas Cepinskas, Marat Slessarev, Claudio M. Martin, Maitray A. Patel, Michael Miller, Eric K. Patterson, David B. O’Gorman, Sean E. Gill, Ian Higgins, Julius P. John, Christopher Melo, Lylia Nini, Xiaoqin Wang, Johannes Zeidler, Jorge A. Cruz-Aguado

Physiology and Pharmacology Publications

Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, is a global health care emergency. Anti-SARS-CoV-2 serological profiling of critically ill COVID-19 patients was performed to determine their humoral response. Blood was collected from critically ill ICU patients, either COVID-19 positive (+) or COVID-19 negative (−), to measure anti-SARS-CoV-2 immunoglobulins: IgM; IgA; IgG; and Total Ig (combined IgM/IgA/IgG). Cohorts were similar, with the exception that COVID-19+ patients had a greater body mass indexes, developed bilateral pneumonias more frequently and suffered increased hypoxia when compared to COVID-19-patients (p < 0.05). The mortality rate for COVID-19+ patients was 50%. COVID-19 status could be determined by anti-SARS-CoV-2 serological responses with excellent classification accuracies on ICU day 1 (89%); ICU day 3 (96%); and ICU days 7 and 10 (100%). The importance of each Ig isotype for determining COVID-19 status on combined ICU days 1 and 3 was: Total Ig, 43%; IgM, 27%; IgA, 24% and IgG, 6%. Peak serological responses for each Ig isotype occurred on different ICU days (IgM day 13 > IgA day 17 > IgG persistently increased), with the Total Ig peaking at approximately ICU day …

The Role Of Panx3 In Age-Associated And Injury-Induced Intervertebral Disc Degeneration, Meaghan Serjeant, Paxton M. Moon, Diana Quinonez, Silvia Penuela, Frank Beier, Cheryle A. Séguin

Physiology and Pharmacology Publications

© 2021 by the authors. Licensee MDPI, Basel, Switzerland. Pannexin 3 (Panx3) is a mechanosensitive, channel-forming glycoprotein implicated in the progression of post-traumatic osteoarthritis. Despite evidence for Panx3 expression in the intervertebral disc (IVD), its function in this cartilaginous joint structure remained unknown. Using Panx3 knockout mice, this study investigated the role of Panx3 in age-associated IVD degeneration and degeneration induced by annulus fibrosus (AF) needle puncture. Loss of Panx3 did not significantly impact the progression of age-associated histopathological IVD degeneration; however, loss of Panx3 was associated with decreased gene expression of Acan, Col1a1, Mmp13 and Runx2 and altered localization …

Are We Missing The Target? Are We Aiming Too Low? What Are The Aerobic Exercise Prescriptions And Their Effects On Markers Of Cardiovascular Health And Systemic Inflammation In Patients With Knee Osteoarthritis? A Systematic Review And Meta-Analysis, Jenna M. Schulz, Trevor B. Birmingham, Hayden F. Atkinson, Emilie Woehrle, Codie A. Primeau, Michael J. Lukacs, Baraa K. Al-Khazraji, Michaela C.M. Khan, Bryn O. Zomar, Robert J. Petrella, Frank Beier, C. Thomas Appleton, J. Kevin Shoemaker, Dianne M. Bryant

Physiology and Pharmacology Publications

© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ. Objectives We systemically reviewed published studies that evaluated aerobic exercise interventions in patients with knee osteoarthritis (OA) to: (1) report the frequency, intensity, type and time (FITT) of exercise prescriptions and (2) quantify the changes in markers of cardiovascular health and systemic inflammation. Data sources PubMed, CINAHL, Scopus; inception to January 2019. Eligibility criteria Randomised clinical trials (RCT), cohort studies, case series. Design We summarised exercise prescriptions for all studies and calculated effect sizes with 95% CIs for between-group (RCTs that compared exercise and …

Inflammation Profiling Of Critically Ill Coronavirus Disease 2019 Patients., Douglas D Fraser, Gediminas Cepinskas, Marat Slessarev, Claudio Martin, Mark Daley, Michael R Miller, David B O'Gorman, Sean E Gill, Eric K Patterson, Claudia C Dos Santos

Physiology and Pharmacology Publications

Objectives: Coronavirus disease 2019 is caused by severe acute respiratory syndrome-coronavirus-2 infection to which there is no community immunity. Patients admitted to ICUs have high mortality, with only supportive therapies available. Our aim was to profile plasma inflammatory analytes to help understand the host response to coronavirus disease 2019.

Design: Daily blood inflammation profiling with immunoassays.

Setting: Tertiary care ICU and academic laboratory.

Subjects: All patients admitted to the ICU suspected of being infected with severe acute respiratory syndrome-coronavirus-2, using standardized hospital screening methodologies, had daily blood samples collected until either testing was confirmed negative on ICU day 3 (coronavirus …

Olive Oil Diet In Mild Pre-Gestational Diabetes Impacts Offspring Β-Cell Development., Bushra Taqui, Farsad Asadi, Evangelina Capobianco, Daniel Barry Hardy, Alicia Jawerbaum, Edith Juliana Arany

Physiology and Pharmacology Publications

Maternal diabetes impairs fetal development and increases the risk of metabolic diseases in the offspring. Previously, we showed maternal dietary supplementation with 6% of olive oil prevents diabetes-induced embryo and fetal defects, in part, through the activation of peroxisome proliferator-activated receptors (PPARs). In this study we examined the effects of this diet on neonatal and adult pancreatic development in both male and female offspring. A mild diabetic model was developed by injecting neonatal rats with streptozotocin (90 mg/kg). During pregnancy these dams were fed a chow diet supplemented or not with 6% olive oil. Dual immunohistochemistry was performed to detect …

Maternal Exposure To Δ9-Tetrahydrocannabinol Impairs Female Offspring Glucose Homeostasis And Endocrine Pancreatic Development In The Rat., Ryan Gillies, Kendrick Lee, Sebastian Vanin, Steven R Laviolette, Alison C Holloway, Edith Arany, Daniel B Hardy

Physiology and Pharmacology Publications

Recent reports indicate that 7% of pregnant mothers in North America use cannabis. This is concerning given that in utero exposure to Δ9-tetrahydrocannabinol (Δ9-THC), the main psychoactive component in cannabis, causes fetal growth restriction and may alter replication and survival of pancreatic β-cells in the offspring. Accordingly, we hypothesized that maternal exposure to Δ9-THC during pregnancy will impair postnatal glucometabolic health of offspring. To test this hypothesis, pregnant Wistar rats were treated with daily intraperitoneal injections of either 3 mg/kg Δ9-THC or vehicle from gestational day 6 to birth. Offspring were subsequently challenged with glucose and insulin at 5 months …

Gsk3787-Loaded Poly(Ester Amide) Particles For Intra-Articular Drug Delivery, Ian J. Villamagna, Danielle M. Mcrae, Aneta Borecki, Xueli Mei, François Lagugné-Labarthet, Frank Beier, Elizabeth Gillies

Physiology and Pharmacology Publications

© 2020 by the authors. Osteoarthritis (OA) is a debilitating joint disorder affecting more than 240 million people. There is no disease modifying therapeutic, and drugs that are used to alleviate OA symptoms result in side effects. Recent research indicates that inhibition of peroxisome proliferator-activated receptor ffi (PPARffi) in cartilage may attenuate the development or progression of OA. PPARffi antagonists such as GSK3787 exist, but would benefit from delivery to joints to avoid side effects. Described here is the loading of GSK3787 into poly(ester amide) (PEA) particles. The particles contained 8 wt. % drug and had mean diameters of about …

Molecular Basis For Activation And Biased Signaling At The Thrombin-Activated Gpcr Proteinase Activated Receptor-4 (Par4), Pierre E. Thibeault, Jordan C. Lesarge, D'Arcy Arends, Michaela Fernandes, Peter Chidiac, Peter B. Stathopulos, Leonard G. Luyt, Rithwik Ramachandran

Physiology and Pharmacology Publications

© 2020 Thibeault et al. Proteinase-activated receptor (PAR)-4 is a member of the proteolytically-activated PAR family of G-protein– coupled receptors (GPCR) that represents an important target in the development of anti-platelet therapeutics. PARs are activated by proteolytic cleavage of their receptor N terminus by enzymes such as thrombin, trypsin, and cathepsin-G. This reveals the receptor-activating motif, termed the tethered ligand that binds intramolecularly to the receptor and triggers signaling. However, PARs are also activated by exogenous application of synthetic peptides derived from the tethered-ligand sequence. To better understand the molecular basis for PAR4-dependent signaling, we examined PAR4-signaling responses to a …

Quantification Of Joint Blood Flow By Dynamic Contrast-Enhanced Near-Infrared Spectroscopy: Application To Monitoring Disease Activity In A Rat Model Of Rheumatoid Arthritis, Seva Ioussoufovitch, Laura B. Morrison, Lise Desjardins, Jennifer A. Hadway, Keith St Lawrence, Ting Yim Lee, Frank Beier, Mamadou Diop

Physiology and Pharmacology Publications

No abstract provided.

Postnatal Catch-Up Growth Leads To Higher P66shc And Mitochondrial Dysfunction., Shelby Oke, Gurjeev Sohi, Daniel Barry Hardy

Physiology and Pharmacology Publications

Epidemiological data suggest an inverse relationship between birth weight and long-term metabolic deficits, which is exacerbated by postnatal catch-up growth. We have previously demonstrated that rat offspring subject to maternal protein restriction (MPR) followed by catch-up growth exhibit impaired hepatic function and ER stress. Given that mitochondrial dysfunction is associated with various metabolic pathologies, we hypothesized that altered expression of p66Shc, a gatekeeper of oxidative stress and mitochondrial function, contributes to the hepatic defects observed in MPR offspring. To test this hypothesis, pregnant Wistar rats were fed a control (20% protein) diet or an isocaloric low protein (8%; LP) diet …

Postnatal Catch-Up Growth Leads To Higher P66shc And Mitochondrial Dysfunction., Shelby Oke, Gurjeev Sohi, Daniel Barry Hardy

Physiology and Pharmacology Publications

Epidemiological data suggest an inverse relationship between birth weight and long-term metabolic deficits, which is exacerbated by postnatal catch-up growth. We have previously demonstrated that rat offspring subject to maternal protein restriction (MPR) followed by catch-up growth exhibit impaired hepatic function and ER stress. Given that mitochondrial dysfunction is associated with various metabolic pathologies, we hypothesized that altered expression of p66Shc, a gatekeeper of oxidative stress and mitochondrial function, contributes to the hepatic defects observed in MPR offspring. To test this hypothesis, pregnant Wistar rats were fed a control (20% protein) diet or an isocaloric low protein (8%; LP) diet …

Exposure To The Rxr Agonist Sr11237 In Early Life Causes Disturbed Skeletal Morphogenesis In A Rat Model, Holly Dupuis, Michael Andrew Pest, Ermina Hadzic, Thin Xuan Vo, Daniel B. Hardy, Frank Beier

Physiology and Pharmacology Publications

© 2019 by the authors. Licensee MDPI, Basel, Switzerland. Longitudinal bone growth occurs through endochondral ossification (EO), controlled by various signaling molecules. Retinoid X Receptor (RXR) is a nuclear receptor with important roles in cell death, development, and metabolism. However, little is known about its role in EO. In this study, the agonist SR11237 was used to evaluate RXR activation in EO. Rats given SR11237 from post-natal day 5 to post-natal day 15 were harvested for micro-computed tomography (microCT) scanning and histology. In parallel, newborn CD1 mouse tibiae were cultured with increasing concentrations of SR11237 for histological and whole-mount evaluation. …

Drug Interactions And Pharmacogenetic Factors Contribute To Variation In Apixaban Concentration In Atrial Fibrillation Patients In Routine Care, Markus Gulilat, Denise Keller, Bradley Linton, A. Demetri Pananos, Daniel Lizotte, George K. Dresser, Jeffrey Alfonsi, Rommel G. Tirona, Richard B. Kim, Ute I. Schwarz

Physiology and Pharmacology Publications

Factor Xa-inhibitor apixaban is an oral anticoagulant prescribed in atrial fibrillation (AF) for stroke prevention. Its pharmacokinetic profile is known to be affected by cytochrome P450 (CYP)3A metabolism, while it is also a substrate of the efflux transporters ATP-binding cassette (ABC)B1 (P-glycoprotein) and ABCG2 (breast cancer resistance protein, BCRP). In this study, we assessed the impact of interacting medication and pharmacogenetic variation to better explain apixaban concentration differences among 358 Caucasian AF patients. Genotyping (ABCG2, ABCB1, CYP3A4*22, CYP3A5*3) was performed by TaqMan assays, and apixaban quantified by mass spectrometry. The typical patient was on average …

Poly(Ester Amide) Particles For Controlled Delivery Of Celecoxib, Ian J. Villamagna, Trent N. Gordon, Mark B. Hurtig, Frank Beier, Elizabeth R. Gillies

Physiology and Pharmacology Publications

© 2019 Wiley Periodicals, Inc. Many potential pharmacological treatments for osteoarthritis can result in undesirable side effects due to the systemic administration of drugs, making the direct delivery of drugs to joints an attractive alternative. Poly(ester amide)s (PEAs) have been shown to exhibit promising properties for the development of particle-based intra-articular delivery vehicles. However, a limited range of PEA structures has been investigated. In this study, we prepared and characterized the properties of two different PEA particles composed of l-phenylalanine, sebacic acid, and either 1,4-butanediol or 1,8-octanediol (PBSe and POSe, respectively). The anti-inflammatory drug celecoxib (CXB) was encapsulated into the …

Δ9-Tetrahydrocannabinol Leads To Endoplasmic Reticulum Stress And Mitochondrial Dysfunction In Human Bewo Trophoblasts., Tina Lojpur, Zachary Easton, Sergio Raez-Villanueva, Steven Laviolette, Alison C Holloway, Daniel B Hardy

Physiology and Pharmacology Publications

While studies have demonstrated that the main psychoactive component of cannabis, Δ9-tetrahydrocannabinol (Δ9-THC) alone induces placental insufficiency and fetal growth restriction, the underlying mechanisms remain elusive. Given that both (i) endoplasmic reticulum (ER) stress in pregnancy and (ii) gestational exposure to Δ9-THC leads to placental deficiency, we hypothesized that Δ9-THC may directly induce placental ER stress, influencing trophoblast gene expression and mitochondrial function. BeWo human trophoblast cells treated with Δ9-THC (3-30 μM) led to a dose-dependent increase in all ER stress markers and CHOP; these effects could be blocked with CB1R/CB2R antagonists. Moreover, expression of ER stress-sensitive genes ERRγ, VEGFA, …

Maternal Protein Restriction During Perinatal Life Affects Lung Mechanics And The Surfactant System During Early Postnatal Life In Female Rats., Reza Khazaee, Lynda A Mccaig, Cory Yamashita, Daniel B Hardy, Ruud A W Veldhuizen

Physiology and Pharmacology Publications

Limited information is available on how fetal growth retardation (FGR) affects the lung in the neonatal period in males and females. This led us to test the hypothesis that FGR alters lung mechanics and the surfactant system during the neonatal period. To test this hypothesis a model of FGR was utilized in which pregnant rat dams were fed a low protein diet during both the gestation and lactation period. We subsequently analyzed lung mechanics using a FlexiVent ventilator in male and female pups at postnatal day 7 and 21. Lung lavage material was obtained at postnatal day 1, 7 and …

Maternal Nicotine Exposure Leads To Augmented Expression Of The Antioxidant Adipose Tissue Triglyceride Lipase Long-Term In The White Adipose Of Female Rat Offspring., Nicole Barra, Taylor Vanduzer, Alison C. Holloway, Daniel B. Hardy

Physiology and Pharmacology Publications

Globally, approximately 10-25% of women smoke during pregnancy. Since nicotine is highly addictive, women may use nicotine containing products like nicotine replacement therapies for smoking cessation, but the long-term consequences of early life exposure to nicotine remain poorly defined. Our laboratory has previously demonstrated that maternal nicotine exposed (MNE) rat offspring exhibit hypertriglyceridemia due to increased hepatic de novo lipogenesis. Hypertriglyceridemia may also be attributed to impaired white adipose tissue (WAT) lipid storage; however, the effects of MNE on WAT are not completely understood. We hypothesize that nicotine-induced alterations in adipose function (e.g. lipid storage) underlie dyslipidemia in MNE adults. …

Maternal Nicotine Exposure Leads To Decreased Cardiac Protein Disulfide Isomerase And Impaired Mitochondrial Function In Male Rat Offspring., Nicole G Barra, Maria Lisyansky, Taylor A Vanduzer, Sandeep Raha, Alison C Holloway, Daniel B Hardy

Physiology and Pharmacology Publications

Smoking throughout pregnancy can lead to complications during gestation, parturition and neonatal development. Thus, nicotine replacement therapies are a popular alternative thought to be safer than cigarettes. However, recent studies in rodents suggest that fetal and neonatal nicotine exposure alone results in cardiac dysfunction and high blood pressure. While it is well known that perinatal nicotine exposure causes increased congenital abnormalities, the mechanisms underlying longer-term deficits in cardiac function are not completely understood. Recently, our laboratory demonstrated that nicotine impairs placental protein disulfide isomerase (PDI) triggering an increase in endoplasmic reticulum stress, leading us to hypothesize that this may also …

Increased Incidence Of Non-Alcoholic Fatty Liver Disease In Male Rat Offspring Exposed To Fluoxetine During Fetal And Neonatal Life Involves The Nlrp3 Inflammasome And Augmented De Novo Hepatic Lipogenesis., Nicole E De Long, Daniel B Hardy, Noelle Ma, Alison C Holloway

Physiology and Pharmacology Publications

Up to 10% of women take selective serotonin reuptake inhibitors (SSRI) during pregnancy. Children exposed to SSRIs in utero have an increased risk of being overweight suggesting that fetal exposure to SSRIs can cause permanent metabolic changes. We have previously shown in rats that fetal and neonatal exposure to the SSRI antidepressant fluoxetine results in metabolic perturbations including increased hepatic triglyceride content; a hallmark of non-alcoholic fatty liver disease (NAFLD). Therefore, the aim of this study was to identify the mechanism(s) underlying the fluoxetine-induced increase in intrahepatic triglyceride content. Female nulliparous Wistar rats were given vehicle or fluoxetine (10 mg/kg/day) …

Maternal Undernutrition And Long-Term Effects On Hepatic Function, Daniel B. Hardy

Physiology and Pharmacology Publications

Undernutrition in utero, regardless of the source, can impair proper liver development leading to long-term metabolic dysfunction. Understanding the molecular mechanisms underlying how nutritional deficits during perinatal life lead to permanent alterations in hepatic gene expression will provide better therapeutic strategies to alleviate the undernourished liver in postnatal life. This chapter addresses the different experimental models of undernutrition in utero, and highlights the direct and indirect mechanisms involved leading to metabolic diseases in the liver. These include hypoxia, oxidative stress, epigenetic alterations, and endoplasmic reticulum (ER) stress. In addition, promising perinatal nutritional and pharmaceutical interventions are highlighted which …

G Protein-Coupled Kiss1 Receptor Is Overexpressed In Triple Negative Breast Cancer And Promotes Drug Resistance., Alexandra Blake, Magdalena Dragan, Rommel G Tirona, Daniel B Hardy, Muriel Brackstone, Alan B Tuck, Andy V Babwah, Moshmi Bhattacharya

Physiology and Pharmacology Publications

Triple-negative breast cancer (TNBC) lacks the expression of estrogen receptor α, progesterone receptor and human epidermal growth factor receptor 2 (HER2). TNBC patients lack targeted therapies, as they fail to respond to endocrine and anti-HER2 therapy. Prognosis for this aggressive cancer subtype is poor and survival is limited due to the development of resistance to available chemotherapies and resultant metastases. The mechanisms regulating tumor resistance are poorly understood. Here we demonstrate that the G protein-coupled kisspeptin receptor (KISS1R) promotes drug resistance in TNBC cells. KISS1R binds kisspeptins, peptide products of the KISS1 gene and in numerous cancers, this signaling pathway …

Positive Allosteric Modulator Of Gabab Receptor Alters Behavioral Effects But Not Afterdischarge Progression Induced By Partial Hippocampal Kindling., L Stan Leung, Miao Jin, Liangwei Chu, Jingyi Ma

Physiology and Pharmacology Publications

Hippocampal seizures decreased the function of GABAB receptors, which may further increase seizure susceptibility and contribute to development of schizophrenia-like behaviors. Recent literature indicates that GABAB receptor agonist may normalize schizophrenia-like behaviors and prevent drug-induced behavioral sensitization. We hypothesized that positive modulation of GABAB receptor function during seizure induction will reduce seizure-induced schizophrenia-like behaviors. Using a partial hippocampal kindling model, afterdischarges were induced after injection of saline or dimethyl sulfoxide (vehicle-kindled rats), or a GABAB receptor positive allosteric modulator CGP7930, at 1 mg/kg i.p. (CGP1-kindled) or 5 mg/kg i.p. (CGP5-kindled). The increase in the primary afterdischarge duration during kindling was …

Associative Spike Timing-Dependent Potentiation Of The Basal Dendritic Excitatory Synapses In The Hippocampus In Vivo., Thomas K Fung, Clayton S Law, L Stan Leung

Physiology and Pharmacology Publications

Spike timing-dependent plasticity in the hippocampus has rarely been studied in vivo. Using extracellular potential and current source density analysis in urethane-anesthetized adult rats, we studied synaptic plasticity at the basal dendritic excitatory synapse in CA1 after excitation-spike (ES) pairing; E was a weak basal dendritic excitation evoked by stratum oriens stimulation, and S was a population spike evoked by stratum radiatum apical dendritic excitation. We hypothesize that positive ES pairing-generating synaptic excitation before a spike-results in long-term potentiation (LTP) while negative ES pairing results in long-term depression (LTD). Pairing (50 pairs at 5 Hz) at ES intervals of -10 …

Nicotine Directly Induces Endoplasmic Reticulum Stress Response In Rat Placental Trophoblast Giant Cells, Michael K. Wong, Alison Holloway C, Daniel B. Hardy

Physiology and Pharmacology Publications

Nicotine exposure during pregnancy leads to placental insufficiency impairing both fetal and neonatal development. Previous studies from our laboratory have demonstrated that in rats,nicotine augmented endoplasmic reticulum (ER) stress in association with placental insufficiency, however, the underlying mechanisms remain elusive. Therefore, we sought to investigate the possible direct effect of nicotine on ER stress in Rcho-1 rat placental trophoblastgiant (TG) cells during differentiation. Protein and/or mRNA expression of markers involved in ER stress (e.g., phosphorylated PERK, eIF2α, CHOP, BiP/GRP78) and trophoblast giant cell differentiation and function (e.g., Pl-1, Pgf, Hsd11b1, and Hsd11b2) were quantified via Western blot or …

Higher Hepatic Mir-29 Expression In Undernourished Male Rats During The Postnatal Period Targets The Long-Term Repression Of Insulin-Like Growth Factor 1, Gurjeev Sohi, Andrew Revesz, Julie Ramkumar, Daniel B. Hardy

Physiology and Pharmacology Publications

A nutritional mismatch in postnatal life of low birth weight offspring increases the risk of developing the metabolic syndrome. Moreover, this is associated with decreased hepatic insulin-like growth factor 1 (Igf1) expression, leading to impaired growth and metabolism. Previously we have demonstrated that the timing of nutritional restoration in perinatal life can differentially programhepatic gene expression. While micro RNAs also play an important role in silencing gene expression, to date, the impact of a nutritional mismatch in neonatal life on their long-term expression has not been evaluated. Given the complementarity of miR-29 to the 3i-UTR of Igf1, we examined how …

Maternal Nicotine Exposure Leads To Impaired Disulfide Bond Formation And Augmented Endoplasmic Reticulum Stress In The Rat Placenta, Michael Wong, Catherine J. Nicholson, Alison C. Holloway, Daniwl Hardy

Physiology and Pharmacology Publications

Maternal nicotine exposure has been associated with many adverse fetal and placental outcomes. Although underlying mechanisms remain elusive, recent studies have identified that augmented endoplasmic reticulum (ER) stress is linked to placental insufficiency. Moreover, ER function depends on proper disulfide bond formation-a partially oxygen-dependent process mediated by protein disulfide isomerase (PDI) and ER oxidoreductases. Given that nicotine compromised placental development in the rat, and placental insufficiency has been associated with poor disulfide bond formation and ER stress, we hypothesized that maternal nicotine exposure leads to both placental ER stress and impaired disulfide bond formation. To test this hypothesis, female Wistar …

Adverse Effects Of Perinatal Nicotine Exposure On Reproductive Outcomes, Daniel B. Hardy, Michael K. Wong

Physiology and Pharmacology Publications

Nicotine exposure during pregnancy through cigarette smoking, nicotine replacement therapies or e-cigarette use continues to be awidespread public health problem, impacting both fetal and postnatal health. Yet, at this time, there remains limited data regarding the safety and efficacy in using these nicotine products during pregnancy. Notably, reports assessing the effect of nicotine exposure on postnatal health outcomes in humans, including reproductive health, are severely lacking. Our current understanding regarding the consequences of nicotine exposure during pregnancy is limited to a few animal studies, which do not comprehensively address the underlying cellular mechanisms involved. This paper aims to critically review …

Waveguide Evanescent Field Scattering Microscopy: Bacterial Biofilms And Their Sterilization Response Via Uv Irradiation, Qamrun Nahar, Frederik Fleiβner, Jeremiah Shuster, Michael Morawitz, Christopher Halfpap, Mihaela Stefan, Uwe Langbein, Gordon Southam, Silvia Mittler

Physiology and Pharmacology Publications

Waveguide Evanescent Field Scattering (WEFS) microscopy is introduced as a new and simple tool for label-free, high contrast imaging of bacteria and bacteria sensors. Bacterial microcolonies and single bacteria were discriminated both by their bright field images and by their evanescent scattering intensity. By comparing bright field images with WEFS images, the proportion of planktonic: sessile (i.e., ‘floating’: attached) bacteria were measured. Bacteria were irradiated with UV light, which limited their biofilm forming capability. A quantitative decrease in attachment of individual, sessile bacteria and in attached, microcolony occupied areas was easily determined within the apparent biofilms with increasing UV dose. …