Animals Commons^™

Surveillance, Epidemiological, And Virological Detection Of Highly Pathogenic H5n1 Avian Influenza Viruses In Duck And Poultry From Bangladesh, Wahedul Karim Ansari, Md Safiullah Parvej, Mohamed E. El Zowalaty, Sally Jackson, Stephen A. Bustin, Adel K. Ibrahim, Md Tanvir Rahman, Han Zhang, Mohammad Ferdousur Rahman Khan, Md Mostakin Ahamd, Md. Fasiur Rahman, Marzia Rahman, Khm Nazmul H. Nazir, Sultan Ahmed, Md Liakot Hossenn, Md Abdul Kafi, Mat Yamage, Nitish C. Debnath, Graba Ahmed, Hossam Ashour, Md Masoud, Ayman Noreddin, Md B. Rahman

Pharmacy Faculty Articles and Research

Avian influenza viruses (AIVs) continue to pose a global threat. Waterfowl are the main reservoir and are responsible for the spillover of AIVs to other hosts. This study was conducted as part of routine surveillance activities in Bangladesh and it reports on the serological and molecular detection of H5N1 AIV subtype. A total of 2169 cloacal and 2191 oropharyngeal swabs as well as 1725 sera samples were collected from live birds including duck and chicken in different locations in Bangladesh between the years of 2013 and 2014. Samples were tested using virus isolation, serological tests and molecular methods of RT-PCR. …

Optimization Of A Genomic Editing System Using Crispr/Cas9-Induced Site-Specific Gene Integration, Jillian L. Mccool Ms., Nick Hum, Gabriela G. Loots

STAR Program Research Presentations

The CRISPR-Cas system is an adaptive immune system found in bacteria which helps protect against the invasion of other microorganisms. This system induces double stranded breaks at precise genomic loci (1) in which repairs are initiated and insertions of a target are completed in the process. This mechanism can be used in eukaryotic cells in combination with sgRNAs (1) as a tool for genome editing. By using this CRISPR-Cas system, in addition to the “safe harbor locus,” ROSAβ26, the incorporation of a target gene into a site that is not susceptible to gene silencing effects can be achieved through few …

High-Sensitivity Mass Spectrometry For Probing Gene Translation In Single Embryonic Cells In The Early Frog (Xenopus) Embryo, Camille Lombard-Banek, Sally Ann Moody, Peter Nemes

Anatomy and Regenerative Biology Faculty Publications

Direct measurement of protein expression with single-cell resolution promises to deepen the understanding of basic molecular processes during normal and impaired development. High-resolution mass spectrometry provides detailed coverage of the proteomic composition of large numbers of cells. Here we discuss recent mass spectrometry developments based on single-cell capillary electrophoresis that extend discovery proteomics to sufficient sensitivity to enable the measurement of proteins in single cells. The single-cell mass spectrometry system is used to detect a large number of proteins in single embryonic cells in blastomeres in the 16-cell embryo of the South African clawed frog (Xenopus laevis) that give rise …

Genetic Analysis Reveals A Hierarchy Of Interactions Between Polycystin-Encoding Genes And Genes Controlling Cilia Function During Left-Right Determination, Daniel T. Grimes, Jennifer L. Keynton, Maria T. Buenavista, Xingjian Jin, Saloni H. Patel, Shinohara Kyosuke, Jennifer Vibert, Debbie J. Williams, Hiroshi Hamada, Rohana Hussain, Surya M. Nauli, Dominic P. Norris

Pharmacy Faculty Articles and Research

During mammalian development, left-right (L-R) asymmetry is established by a cilia-driven leftward fluid flow within a midline embryonic cavity called the node. This ‘nodal flow’ is detected by peripherally-located crown cells that each assemble a primary cilium which contain the putative Ca²⁺ channel PKD2. The interaction of flow and crown cell cilia promotes left side-specific expression of Nodal in the lateral plate mesoderm (LPM). Whilst the PKD2-interacting protein PKD1L1 has also been implicated in L-R patterning, the underlying mechanism by which flow is detected and the genetic relationship between Polycystin function and asymmetric gene expression remains unknown. Here, we …

Assessment Of Daf-19 Related Behavioral Defects, Loraina A. Stinson

Lawrence University Honors Projects

The daf-19 gene encodes the only RFX transcription factors in C. elegans, producing at least four related protein isoforms, one of which, DAF-19C, is responsible for ciliogenesis. Previous work by Senti and Swoboda (2008) demonstrated that adult worms deficient in all four DAF-19 proteins have extremely aberrant dwelling and roaming behavior on bacterial food. Most intriguingly, the addition of cDNA encoding the DAF-19C isoform restores cilia formation, but does not fully restore wild-type dwelling and roaming behavior. We are suggesting that additional neuron functions are needed to properly execute behaviors and these neuron functions require the activity of other …

Programming Heart Disease: Does Poor Maternal Nutrition Alter Expression Of Cardiac Markers Of Proliferation, Hypertrophy, And Fibrosis In Offspring?, Cathy Chun

Honors Scholar Theses

Maternal malnutrition can affect fetal organogenesis, metabolic processes, and factors involved in developmental regulation. Of the many physiological effects poor maternal nutrition can induce in offspring, one of the most important organs affected is the heart. Cardiovascular disease has been associated with poor maternal diet. It also been suggested that hypertension can originate during impaired intrauterine growth and development. Hypertension can trigger hypertensive heart disease and is associated with numerous heart complications. We hypothesized that poor maternal nutrition would alter critical growth factors associated with normal heart development, specifically, insulin-like growth factor (IGF)-1, IGF-2, transforming growth factor (TGF)β, and connective …

The Roles Of Malt1 In Nf-Κb Activation And Solid Tumor Progression, Deng Pan

Dissertations and Theses (Open Access)

The transcription factor NF-κB plays a central role in many aspects of biological processes and diseases, such as inflammation and cancer. Although it has been suggested thatNF-κB is critical in tumorigenesis and tumor progression, the molecular mechanism by which NF-κB is activated in solid tumor remains largely unknown. In the current work, we focus on growth factor receptor-induced NF-κB activation and tumor progression, including epidermal growth factor receptor (EGFR)-induced NF-κB in lung cancer and heregulin receptor (HER2)-induced NF-κB in breast cancer. We found that Mucosa-associated lymphoma translocation protein 1 (MALT1), also known as paracaspase, is required for EGFR-induced NF-κB activation …

The Effect Of Nitrate On The Release Of Glucose Into The Hemolymph Of Crayfish, Procambarus Clarkii, Alec R. Flores, Lee Kats, David Green, Gary Bucciarelli

Seaver College Research And Scholarly Achievement Symposium

Pollutants can change the behaviors of invertebrate stream animals. The level of one common pollutant, nitrate (NO3), has been rising in many local rivers and streams throughout the United States due to increases in anthropogenic sources. Nitrate, heavily regulated for its toxic effects to human health, namely the aiding in the development of cancer, also dangerously affects aquatic species by converting oxygen-carrying pigments to forms that are incapable of carrying oxygen. To understand the stress effects of ambient nitrate exposure on P. clarkii, we collected hemolymph samples from red swamp crayfish (Procambarus clarkii) over a 48-hour period after exposure to …

Localized Jnk Signaling Regulates Organ Size During Development., Helen Rankin Willsey, Xiaoyan Zheng, José Carlos Pastor-Pareja, A Jeremy Willsey, Philip A Beachy, Tian Xu

Anatomy and Regenerative Biology Faculty Publications

A fundamental question of biology is what determines organ size. Despite demonstrations that factors within organs determine their sizes, intrinsic size control mechanisms remain elusive. Here we show that Drosophila wing size is regulated by JNK signaling during development. JNK is active in a stripe along the center of developing wings, and modulating JNK signaling within this stripe changes organ size. This JNK stripe influences proliferation in a non-canonical, Jun-independent manner by inhibiting the Hippo pathway. Localized JNK activity is established by Hedgehog signaling, where Ci elevates dTRAF1 expression. As the dTRAF1 homolog, TRAF4, is amplified in numerous cancers, these …

Single-Cell Mass Spectrometry For Discovery Proteomics: Quantifying Translational Cell Heterogeneity In The 16-Cell Frog (Xenopus) Embryo, Camille Lombard-Banek, Sally Ann Moody, Peter Nemes

Anatomy and Regenerative Biology Faculty Publications

We advance mass spectrometry from a cell population-averaging tool to one capable of quantifying the expression of diverse proteins in single embryonic cells. Our instrument combines capillary electrophoresis (CE), electrospray ionization, and a tribrid ultrahigh-resolution mass spectrometer (HRMS) to enable untargeted (discovery) proteomics with ca. 25 amol lower limit of detection. CE-μESI-HRMS enabled the identification of 500–800 nonredundant protein groups by measuring 20 ng, or <0.2% of the total protein content in single blastomeres that were isolated from the 16-cell frog (Xenopus laevis) embryo, amounting to a total of 1709 protein groups identified between n=3 biological replicates. By quantifying ≈150 nonredundant protein groups between all blastomeres and replicate measurements, we found significant translational cell heterogeneity along multiple axes of the embryo at this very early stage of development when the transcriptional program of the embryo has yet to begin.

Thinking Pigs: Cognition, Emotion, And Personality, Lori Marino, Christina M. Colvin

Mammalogy Collection

An exploration of the cognitive complexity of Sus domesticus, the domestic pig.

Chronic Pancreatitis, Pain, And Anxiety In An Alcohol And High Fat Mouse Model, Tiffanie Clinkinbeard

Theses and Dissertations--Gerontology

Homeodynamic space (HDS) shrinks as vulnerability increases with aging and repeated damage to the cells. HDS is lost in alcoholic pancreatitis patients due to overconsumption of alcohol, smoking, and high fat diets. Etiologically relevant animal models for study of chronic pancreatitis (CP) are needed. In order to begin filling this gap a central purpose of this dissertation research was to examine relationships between the alcohol and high fat diet (AHF) and pancreatitis with attention to hypersensitivity and anxiety-like behaviors. The AHF diet induced pancreatitis described here etiologically mimics human risk factors of AHF consumption for advancement to alcoholic CP.

In …

Epigenetic Modification Prevents Excessive Wound Healing And Scar Formation After Glaucoma Filtration Surgery, Ajay Sharma, Govindaraj Anumanthan, Marcos Reyes, Huiyi Chen, Jason W. Brubaker, Saad Siddiqui, Suneel Gupta, Frank G. Rieger, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

PURPOSE. The purpose of this study was to determine the efficacy of suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor (HDACi), in prevention of excessive wound healing and scar formation in a rabbit model of glaucoma filtration surgery (GFS).

METHODS. A rabbit model of GFS was used. Rabbits that underwent GFS received balanced salt solution, or SAHA (50 lM), or mitomycin C (0.02%). Clinical scores of IOP, bleb vascularity, and slit-lamp examination were performed. On postoperative day 14, rabbits were killed and the bleb tissues were collected for evaluation of tissue fibrosis with hematoxylin and eosin, Masson trichrome, a-smooth muscle …

Development Of A Novel In Vivo Corneal Fibrosis Model In The Dog, K. M. Gronkiewicz, Elizabeth A. Giuliano, K. Kuroki, F. Bunyak, Ajay Sharma, L. B. C. Teixeira, C. W. Hamm, R. R. Mohan

Pharmacy Faculty Articles and Research

The aim of this study was to develop a novel in vivo corneal model of fibrosis in dogs utilizing alkali burn and determine the ability of suberanilohydroxamic acid (SAHA) to inhibit corneal fibrosis using this large animal model. To accomplish this, we used seven research Beagle dogs. An axial corneal alkali burn in dogs was created using 1 N NaOH topically. Six dogs were randomly and equally assigned into 2 groups: A) vehicle (DMSO, 2 μL/mL); B) anti-fibrotic treatment (50 μM SAHA). The degree of corneal opacity, ocular health, and anti-fibrotic effects of SAHA were determined utilizing the Fantes grading …

Molecular Mechanisms Of Suberoylanilide Hydroxamic Acid In The Inhibition Of Tgf-Β1-Mediated Canine Corneal Fibrosis, Kristina M. Gronkiewicz, Elizabeth A. Giuliano, Ajay Sharma, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

Objective—To investigate molecular mechanisms mediating anti-fibrotic effect of SAHA in the canine cornea using an in vitro model. We hypothesized that SAHA attenuates corneal fibrosis by modulating Smad-dependent and, to a lesser extent, Smad-independent signaling pathways activated by TGF-β1, as well as matrix metalloproteinase (MMP) activity.

Methods—Cultured canine corneal fibroblasts (CCF) were incubated in the presence/absence of TGF-β1 (5ng/ml) and SAHA (2.5μM) for 24hrs. Western blot analysis was used to quantify non-phosphorylated and phosphorylated isoforms of Smad2/3, p38 MAP kinase (MAPK), ERK1/2 and JNK1. Real-time PCR and zymography were utilized to quantify MMP1, MMP2, MMP8 and MMP9 mRNA expression and …

Cross-Sectional Analysis Of Salivary Cortisol And Cyathostome Infestation In Horses, Danielle L. Keating

Undergraduate Honors Thesis Projects

With an increase in anthelmintic resistance and decreased efficacy of many commercial dewormers, understanding factors that contribute to parasite infestations in horses is integral to their management. The goal of this study was to look at the potential relationship between parasites and stress response by evaluating salivary cortisol levels and cyathostome egg shedding levels. Using a sample size of n = 200 horses from the state of Ohio, fecal and saliva samples were collected from each horse. Fecal egg counts were performed for each horse with a modified Stoll method, and saliva samples were tested with an enzyme-linked immunosorbent assay …

Animal Mourning: Précis Of How Animals Grieve (King 2013), Barbara J. King

Animal Sentience

Abstract: When an animal dies, that individual’s mate, relatives, or friends may express grief. Changes in the survivor’s patterns of social behavior, eating, sleeping, and/or of expression of affect are the key criteria for defining grief. Based on this understanding of grief, it is not only big-brained mammals like elephants, apes, and cetaceans who can be said to mourn, but also a wide variety of other animals, including domestic companions like cats, dogs, and rabbits; horses and farm animals; and some birds. With keen attention placed on seeking where grief is found to occur and where it is absent …

Negative Skeletal Effects Of Locally Produced Adiponectin, Marcia J. Abbott, Theresa M. Roth, Linh Ho, Liping Wang, Dylan O'Carroll, Robert A. Nissenson

Health Sciences and Kinesiology Faculty Articles

Epidemiological studies show that high circulating levels of adiponectin are associated with low bone mineral density. The effect of adiponectin on skeletal homeostasis, on osteoblasts in particular, remains controversial. We investigated this issue using mice with adipocyte-specific over-expression of adiponectin (AdTg). MicroCT and histomorphometric analysis revealed decreases (15%) in fractional bone volume in AdTg mice at the proximal tibia with no changes at the distal femur. Cortical bone thickness at mid-shafts of the tibia and at the tibiofibular junction was reduced (3–4%) in AdTg mice. Dynamic histomorphometry at the proximal tibia in AdTg mice revealed inhibition of bone formation. AdTg …

Effects Of Human Recreational Activity On The Tameness Of Common Loons (Gavia Immer) In Northern Wisconsin, Seth Yund

Student Scholar Symposium Abstracts and Posters

The Common Loon (Gavia immer) is an aquatic diving bird that lives in freshwater habitats in Canada and the northern U.S.. Human activity on a loon’s resident lake may affect its fitness and behavior, yet few studies identify or quantify these effects. We modified existing techniques that measure escape distances in other species to measure tameness as the distance at which individual loons dove in response to human approach by canoe. Tameness was similar between pair members, suggesting that common lake conditions or the behavior of a mate might influence the behavior. Sex, size within sex, and human activity did …

Comparative Analysis Of Anti-Bd Bacteria From Six Malagasy Frog Species Of Ranomafana National Park, Kelsey Savage

Senior Honors Projects, 2010-2019

As Malagasy amphibians are facing an impending extinction crisis from the lethal skin fungus Batrachochytrium dendrobatidis (Bd), it has become imperative to proactively mitigate the threat. Bd sporangia develop in the skin of infected amphibians and cause the skin to thicken, leading to ionic imbalance and eventual heart failure. It has been shown that certain bacterial species are able to inhibit Bd growth on amphibians by producing antifungal metabolites. Community-based probiotics are one approach used to combat chytridomycosis by inoculating an environment with Bd-inhibitory bacteria so that many amphibian species are treated at once. With this method, it is important …

Effect Of Novel Dietary Supplement On Metabolism In Vitro And In Vivo, Robert A. Vaughan, Ailish C. White, Jason R. Beam, Nicholas P. Gannon, Randi Garcia-Smith, Roy M. Salgado, Marco Bisoffi, Kristina A. Trujillo, Carole A. Conn, Christine M. Mermier

Health Sciences and Kinesiology Faculty Articles

Obesity is an increasingly prevalent and preventable morbidity with multiple behavioral, surgical and pharmacological interventions currently available. Commercial dietary supplements are often advertised to stimulate metabolism and cause rapid weight and/or fat loss, although few well-controlled studies have demonstrated such effects. We describe a commercially available dietary supplement (purportedly containing caffeine, catechins, and other metabolic stimulators) on resting metabolic rate in humans, and on metabolism, mitochondrial content, and related gene expression in vitro. Human males ingested either a placebo or commercially available supplement (RF) in a randomized double-blind placebo-controlled cross-over fashion. Metabolic rate, respiratory exchange ratio, and blood pressure were …

Live Imaging Of The Ependymal Cilia In The Lateral Ventricles Of The Mouse Brain, Alzahra J. Al Omran, Hannah C. Saternos, Tongyu Liu, Surya M. Nauli, Wissam A. Aboualaiwi

Pharmacy Faculty Articles and Research

Multiciliated ependymal cells line the ventricles in the adult brain. Abnormal function or structure of ependymal cilia is associated with various neurological deficits. The current ex vivo live imaging of motile ependymal cilia technique allows for a detailed study of ciliary dynamics following several steps. These steps include: mice euthanasia with carbon dioxide according to protocols of The University of Toledo’s Institutional Animal Care and Use Committee (IACUC); craniectomy followed by brain removal and sagittal brain dissection with a vibratome or sharp blade to obtain very thin sections through the brain lateral ventricles, where the ependymal cilia can be visualized. …

Effects Of Cannabidiol On Contractions And Calcium Signaling In Rat Ventricular Myocytes, Ramez M. Ali, Lina T. Al Kury, Keun-Hang Susan Yang, Anwar Qureshi, Mohanraj Rajesh, Sehamuddin Galadari, Yaroslav M. Shuba, Frank Christopher Howarth, Murat Oz

Mathematics, Physics, and Computer Science Faculty Articles and Research

Cannabidiol (CBD), a major nonpsychotropic cannabinoid found in Cannabis plant, has been shown to influence cardiovascular functions under various physiological and pathological conditions. In the present study, the effects of CBD on contractility and electrophysiological properties of rat ventricular myocytes were investigated. Video edge detection was used to measure myocyte shortening. Intracellular Ca2+ was measured in cells loaded with the Ca2+ sensitive fluorescent indicator fura-2 AM. Whole-cell patch clamp was used to measure action potential and Ca2+ currents. Radioligand binding was employed to study pharmacological characteristics of CBD binding. CBD (1 μM) caused a significant decrease in the amplitudes of …

Extraordinary Diversity Of Immune Response Proteins Among Sea Urchins: Nickel-Isolated Sp185/333 Proteins Show Broad Variations In Size And Charge., Lauren S. Sherman, Catherine S. Schrankel, Kristy J. Brown, L. Courtney Smith

Pediatrics Faculty Publications

Effective protection against pathogens requires the host to produce a wide range of immune effector proteins. The Sp185/333 gene family, which is expressed by the California purple sea urchin Strongylocentrotus purpuratus in response to bacterial infection, encodes a highly diverse repertoire of anti-pathogen proteins. A subset of these proteins can be isolated by affinity to metal ions based on multiple histidines, resulting in one to four bands of unique molecular weight on standard Western blots, which vary depending on the individual sea urchin. Two dimensional gel electrophoresis (2DE) of nickel-isolated protein samples followed by Western blot was employed to detect …

Segregation Of Information About Emotional Arousal And Valence In Horse Whinnies, Elodie F. Briefer, Anne-Laure Maigrot, Roi Mandel, Sabrina Briefer Freymond, Iris Bachmann, Edna Hillmann

Sentience Collection

Studying vocal correlates of emotions is important to provide a better understanding of the evolution of emotion expression through cross-species comparisons. Emotions are composed of two main dimensions: emotional arousal (calm versus excited) and valence (negative versus positive). These two dimensions could be encoded in different vocal parameters (segregation of information) or in the same parameters, inducing a trade-off between cues indicating emotional arousal and valence. We investigated these two hypotheses in horses. We placed horses in five situations eliciting several arousal levels and positive as well as negative valence. Physiological and behavioral measures collected during the tests suggested the …

Proof-Of-Concept Of Environmental Dna Tools For Atlantic Sturgeon Management, Jameson Hinkle

Theses and Dissertations

Abstract

The Atlantic Sturgeon (Acipenser oxyrinchus oxyrinchus, Mitchell) is an anadromous species that spawns in tidal freshwater rivers from Canada to Florida. Overfishing, river sedimentation and alteration of the river bottom have decreased Atlantic Sturgeon populations, and NOAA lists the species as endangered. Ecologists sometimes find it difficult to locate individuals of a species that is rare, endangered or invasive. The need for methods less invasive that can create more resolution of cryptic species presence is necessary. Environmental DNA (eDNA) is a non-invasive means of detecting rare, endangered, or invasive species by isolating nuclear or mitochondrial DNA (mtDNA) from the …

Role Of 5'Tg3'-Interacting Factors (Tgifs) In Vorinostat (Hdac Inhibitor)-Mediated Corneal Fibrosis Inhibition, Ajay Sharma, Nishant R. Sinha, Saad Siddiqui, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

Purpose: We have previously reported that vorinostat, an FDA-approved, clinically used histone deacetylase (HDAC) inhibitor, attenuates corneal fibrosis in vivo in rabbits by blocking transforming growth factor β (TGFβ). The 5′TG3′-interacting factors (TGIFs) are transcriptional repressors of TGFβ1 signaling via the Smad pathway. The present study was designed to explore the expression of TGIFs in human corneal fibroblasts and to investigate their role in mediating the antifibrotic effect of vorinostat.

Methods: Human corneal fibroblast cultures were generated from donor corneas. RNA isolation, cDNA preparation, and PCR were performed to detect the presence of TGIF1 and TGIF2 transcripts. The cultures were …

Expression Pattern And Biochemical Properties Of Zebrafish N-Acetylglutamate Synthase, Ljubica Caldovic, Nantaporn Haskins, Amy Mumo, Himani Majumdar, Mary Pinter, Mendel Tuchman, Alison Krufka

Genomics and Precision Medicine Faculty Publications

The urea cycle converts ammonia, a waste product of protein catabolism, into urea. Because fish dispose ammonia directly into water, the role of the urea cycle in fish remains unknown. Six enzymes, N-acetylglutamate synthase (NAGS), carbamylphosphate synthetase III, ornithine transcarbamylase, argininosuccinate synthase, argininosuccinate lyase and arginase 1, and two membrane transporters, ornithine transporter and aralar, comprise the urea cycle. The genes for all six enzymes and both transporters are present in the zebrafish genome. NAGS (EC 2.3.1.1) catalyzes the formation of N-acetylglutamate from glutamate and acetyl coenzyme A and in zebrafish is partially inhibited by L-arginine. NAGS and other urea …

Connecting Model Species To Nature: Predator-Induced Long-Term Sensitization In Aplysia Californica, Maria J. Mason, Amanda J. Watkins, Jordann Wakabayashi, Jennifer Buechler, Christine Pepino, Michelle Brown, William G. Wright

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Previous research on sensitization in Aplysia was based entirely on unnatural noxious stimuli, usually electric shock, until our laboratory found that a natural noxious stimulus, a single sublethal lobster attack, causes short-term sensitization. We here extend that finding by demonstrating that multiple lobster attacks induce long-term sensitization (>= 24 h) as well as similar, although not identical, neuronal correlates as observed after electric shock. Together these findings establish long-and short-term sensitization caused by sublethal predator attack as a natural equivalent to sensitization caused by artificial stimuli.

Parent-Metabolite Pharmacokinetic Models For Tramadol – Tests Of Assumptions And Predictions, Sam Holford, Karel Allegaert, Brian J. Anderson, Butch Kukanich, Altamir B. Sousa, Amir Steinman, Bruno Pypendop, Reza Mehvar, Mario Giorgi, Nick Holford

Pharmacy Faculty Articles and Research

Allometric principles were used to discern cross-species differences in (±)-tramadol disposition and formation of its primary analgesic metabolite, (±)-O-desmethyl-tramadol (M1). Species differences in formation of M1 may help predict the analgesic effectiveness of tramadol. Tramadol was administered intravenously by a zero-order (constant infusion) process or rapid bolus dose and racemic concentrations of tramadol and M1 measured. Data were pooled to define differences between species (human, rat, cat, dog, goat, donkey and horse). A two-compartment linear disposition model with first-order elimination was used to describe tramadol and M1 disposition. Slow metabolizers were detected in 6% of the population and tramadol clearance …