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Veterinary Toxicology and Pharmacology Commons

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A Review Of Relevant Therapeutic Targets For The Management Of Congestive Heart Failure In Dogs: Present And Future Directions, Jonathan P. Mochel 2019 Iowa State University

A Review Of Relevant Therapeutic Targets For The Management Of Congestive Heart Failure In Dogs: Present And Future Directions, Jonathan P. Mochel

Jonathan Mochel

Congestive heart failure (CHF) is a major cause of morbidity and mortality with an increasing prevalence in human and canine populations. Similar to humans, overactivation of the renin-angiotensin aldosterone system is involved in the pathophysiology of CHF in dogs. Current therapeutic strategies for the management of canine CHF include the use of RAAS inhibitors, diuretics and inodilators. The present review summarizes data from our own research on the modulation of the renin-angiotensin cascade in dogs in dogs, together with new findings (including novel therapeutic targets) from the veterinary and the human literature.


Pentablock Copolymer Micelle Nanoadjuvants Enhance Cytosolic Delivery Of Antigen And Improve Vaccine Efficacy While Inducing Low Inflammation, Sujata Senapati, Ross J. Darling, Darren Loh, Ian C. Schneider, Michael J. Wannemeuhler, Balaji Narasimhan, Surya K. Mallapragada 2019 Iowa State University

Pentablock Copolymer Micelle Nanoadjuvants Enhance Cytosolic Delivery Of Antigen And Improve Vaccine Efficacy While Inducing Low Inflammation, Sujata Senapati, Ross J. Darling, Darren Loh, Ian C. Schneider, Michael J. Wannemeuhler, Balaji Narasimhan, Surya K. Mallapragada

Chemistry Publications

As the focus has shifted from traditional killed or live, attenuated vaccines towards subunit vaccines, improvements in vaccine safety have been confronted with low immunogenicity of protein antigens. This issue has been addressed by synthesizing and designing a wide variety of antigen carriers and adjuvants, such as Toll-like receptor agonists (e.g., MPLA, CpG). Studies have focused on optimizing adjuvants for improved cellular trafficking, cytosolic availability, and improved antigen presentation. In this work, we describe the design of novel amphiphilic pentablock copolymer (PBC) adjuvants that exhibit high biocompatibility and reversible pH- and temperature-sensitive micelle formation. We demonstrate improved humoral immunity ...


The Role Of The Gut-Brain Axis In Neurodegenerative Diseases And Relevance Of The Canine Model: A Review, Yoko Ambrosini, Dana Borcherding, Anumantha Kanthasamy, Hyun Jung Kim, Albert Jergens, Karin Allenspach, Jonathan Mochel 2019 Iowa State University

The Role Of The Gut-Brain Axis In Neurodegenerative Diseases And Relevance Of The Canine Model: A Review, Yoko Ambrosini, Dana Borcherding, Anumantha Kanthasamy, Hyun Jung Kim, Albert Jergens, Karin Allenspach, Jonathan Mochel

Biomedical Sciences Publications

Identifying appropriate animal models is critical in developing translatable in vitro and in vivo systems for therapeutic development and investigating disease pathophysiology. These animal models should have direct biological and translational relevance to the underlying disease they are supposed to mimic. Aging dogs naturally develop a cognitive decline in many aspects including learning and memory, but also exhibit human-like individual variability in the aging process. Neurodegenerative processes that can be observed in both human and canine brains include the progressive accumulation of β-amyloid (Aβ) found as diffuse plaques in the prefrontal cortex, including the gyrus proreus, the hippocampus, and in ...


A Review Of Relevant Therapeutic Targets For The Management Of Congestive Heart Failure In Dogs: Present And Future Directions, Jonathan P. Mochel 2019 Iowa State University

A Review Of Relevant Therapeutic Targets For The Management Of Congestive Heart Failure In Dogs: Present And Future Directions, Jonathan P. Mochel

Biomedical Sciences Publications

Congestive heart failure (CHF) is a major cause of morbidity and mortality with an increasing prevalence in human and canine populations. Similar to humans, overactivation of the renin-angiotensin aldosterone system is involved in the pathophysiology of CHF in dogs. Current therapeutic strategies for the management of canine CHF include the use of RAAS inhibitors, diuretics and inodilators. The present review summarizes data from our own research on the modulation of the renin-angiotensin cascade in dogs in dogs, together with new findings (including novel therapeutic targets) from the veterinary and the human literature.


Impact Of Flow Rate, Collection Devices, And Extraction Methods On Tear Concentrations Following Oral Administration Of Doxycycline In Dogs And Cats, Lionel Sebbag, Lucas Showman, Emily M. McDowell, Ann Perera, Jonathan P. Mochel 2018 Iowa State University

Impact Of Flow Rate, Collection Devices, And Extraction Methods On Tear Concentrations Following Oral Administration Of Doxycycline In Dogs And Cats, Lionel Sebbag, Lucas Showman, Emily M. Mcdowell, Ann Perera, Jonathan P. Mochel

Veterinary Diagnostic and Production Animal Medicine Publications

Purpose: Compare the precision of doxycycline quantification in tear fluid collected with either Schirmer strips or polyvinyl acetal (PVA) sponges following oral drug administration.

Methods: Three dogs and 3 cats were administered doxycycline orally at a dose of 4.2–5 mg/kg every 12 h for 6 consecutive days. At day 5 and 6, blood and tear fluid were sampled to capture doxycycline trough and maximal concentrations. Tear fluid was collected 3 times (spaced 10 min apart) at each session with the absorbent material placed in the lower conjunctival fornix until the 20-mm mark was reached (Schirmer strip, one ...


The Study Design Elements Employed By Researchers In Preclinical Animal Experiments From Two Research Domains And Implications For Automation Of Systematic Reviews, Annette M. O'Connor, Sarah C. Totton, Jonah C. Cullen, Mahmood Ramezani, Vijay Kalivarapu, Chaohui Yuan, Stephen B. Gilbert 2018 Iowa State University

The Study Design Elements Employed By Researchers In Preclinical Animal Experiments From Two Research Domains And Implications For Automation Of Systematic Reviews, Annette M. O'Connor, Sarah C. Totton, Jonah C. Cullen, Mahmood Ramezani, Vijay Kalivarapu, Chaohui Yuan, Stephen B. Gilbert

Veterinary Diagnostic and Production Animal Medicine Publications

Systematic reviews are increasingly using data from preclinical animal experiments in evidence networks. Further, there are ever-increasing efforts to automate aspects of the systematic review process. When assessing systematic bias and unit-of-analysis errors in preclinical experiments, it is critical to understand the study design elements employed by investigators. Such information can also inform prioritization of automation efforts that allow the identification of the most common issues. The aim of this study was to identify the design elements used by investigators in preclinical research in order to inform unique aspects of assessment of bias and error in preclinical research. Using 100 ...


30-Day Oral Acetaminophen Tolerance In Adult Horses, Sarah E. Foreman 2018 Augustana College, Rock Island Illinois

30-Day Oral Acetaminophen Tolerance In Adult Horses, Sarah E. Foreman

Celebration of Learning

There are no controlled studies of acetaminophen toxicity in horses. The objective was to test the hypotheses that oral acetaminophen administered at a dosage 25% higher than that sometimes used in horses would result in measurable hepatic toxicity as seen in humans and other species. Six healthy adult horses were administered 25 mg/kg acetaminophen powder in corn syrup twice daily for 30 days. Three other horses served as negative controls receiving only corn syrup. Jugular venous blood samples were obtained on days 7 and 1 before treatment; on treatment days 1, 2, 5, 8, 12, 15, 19, 22, 26 ...


Immunostimulatory Effects Of Antigen-Conjugated Inp/Zns Quantum Dot Nanoparticles In An Avian Model, Christopher Lyle 2018 University of Arkansas, Fayetteville

Immunostimulatory Effects Of Antigen-Conjugated Inp/Zns Quantum Dot Nanoparticles In An Avian Model, Christopher Lyle

Theses and Dissertations

Due to their unique physicochemical and enhanced immunostimulatory properties, quantum dot (QD) nanoparticles have shown increasing promise in biomedical research applications including bioimaging, drug delivery, and as vaccine adjuvants. Toxicity, however, remains a concern for the use of QD in these applications and thus, there is an increased demand for effective in vitro and in vivo systems to measure the bioactivity of QD. In this study in vitro and in vivo chicken models were used to investigate the effects of QD on innate and adaptive immunity. Chicken macrophage cultures were treated in vitro with QD to measure macrophage activation and ...


Lack Of Effect Of A Topical Regenerative Agent On Re-Epithelialization Rate Of Canine Spontaneous Chronic Corneal Epithelial Defects: A Randomized, Double-Masked, Placebo-Controlled Study, Lionel Sebbag, Rachel A. Allbaugh, Travis Strong, Rachel Strauss, Rita F. Wehrman, Braidee C. Foote, Chimene S. Peterson, Gil Ben-Shlomo 2018 Iowa State University

Lack Of Effect Of A Topical Regenerative Agent On Re-Epithelialization Rate Of Canine Spontaneous Chronic Corneal Epithelial Defects: A Randomized, Double-Masked, Placebo-Controlled Study, Lionel Sebbag, Rachel A. Allbaugh, Travis Strong, Rachel Strauss, Rita F. Wehrman, Braidee C. Foote, Chimene S. Peterson, Gil Ben-Shlomo

Veterinary Clinical Sciences Publications

Spontaneous chronic corneal epithelial defects (SCCEDs) are characteristic ulcers in dogs that are refractory to healing. The aim of the study was to evaluate the use of a topical regenerative agent to promote healing of SCCEDs. Nineteen dogs (20 eyes) were randomized to receive either regenerative agent (10 eyes) or placebo (10 eyes) every 48 h following corneal debridement, which was repeated 1 week later if the SCCED had not yet healed. The mean ± standard deviation time to re-epithelialization was 17.3 ± 12.8 days for the group treated with a topical regenerative agent and 19.3 ± 11.7 days ...


A Single Dose Polyanhydride-Based Vaccine Platform Promotes And Maintains Anti-Gnrh Antibody Titers, Robert G. Schaut, Matt T. Brewer, Jesse M. Hostetter, Kriscelle Mendoza, Julia E. Vela-Ramirez, Sean M. Kelly, John K. Jackman, Giuseppe Dell’Anna, Joan M. Howard, Balaji Narasimhan, Wen Zhou, Douglas E. Jones 2018 United States Department of Agriculture

A Single Dose Polyanhydride-Based Vaccine Platform Promotes And Maintains Anti-Gnrh Antibody Titers, Robert G. Schaut, Matt T. Brewer, Jesse M. Hostetter, Kriscelle Mendoza, Julia E. Vela-Ramirez, Sean M. Kelly, John K. Jackman, Giuseppe Dell’Anna, Joan M. Howard, Balaji Narasimhan, Wen Zhou, Douglas E. Jones

Veterinary Pathology Publications and Papers

Traditionally, vaccination strategies require an initial priming vaccination followed by an antigen boost to generate adequate immunity. Here we describe vaccination against a self-peptide for reproductive sterilization utilizing a three-stage vaccine platform consisting of gonadotropin releasing hormone multiple antigenic peptide (GnRH-MAP) as a soluble injection coupled with subcutaneous administration of polyanhydride-immobilized GnRH-MAP and a cyto-exclusive implant containing GnRH-MAP dendrimer-loaded polyanhydride. This strategy generated and maintained cell-mediated and humoral immunity for up to 41 weeks after a single vaccination in mice with enhanced antibody avidity over time. All intact implants had a grossly visible tissue interface with neovascularization and lymphocytic aggregates ...


Detection Of Porcine Reproductive And Respiratory Syndrome Virus (Prrsv)-Specific Igm-Iga In Oral Fluid Samples Reveals Prrsv Infection In The Presence Of Maternal Antibody, Marisa L. Rotolo, Luis Giménez-Lirola, Ju Ji, Ronaldo Magtoto, Yuly A. Henao-Díaz, Chong Wang, David H. Baum, Karen M. Harmon, Rodger G. Main, Jeffrey J. Zimmerman 2018 Iowa State University

Detection Of Porcine Reproductive And Respiratory Syndrome Virus (Prrsv)-Specific Igm-Iga In Oral Fluid Samples Reveals Prrsv Infection In The Presence Of Maternal Antibody, Marisa L. Rotolo, Luis Giménez-Lirola, Ju Ji, Ronaldo Magtoto, Yuly A. Henao-Díaz, Chong Wang, David H. Baum, Karen M. Harmon, Rodger G. Main, Jeffrey J. Zimmerman

Statistics Publications

The ontogeny of PRRSV antibody in oral fluids has been described using isotype-specific ELISAs. Mirroring the serum response, IgM appears in oral fluid by 7 days post inoculation (DPI), IgA after 7 DPI, and IgG by 9 to 10 DPI. Commercial PRRSV ELISAs target the detection of IgG because the higher concentration of IgG relative to other isotypes provides the best diagnostic discrimination. Oral fluids are increasingly used for PRRSV surveillance in commercial herds, but in younger pigs, a positive ELISA result may be due either to maternal antibody or to antibody produced by the pigs in response to infection ...


The Efficacy Of Antibiotic Treatments In Dairy Cows At Dry-Off To Prevent New Intramammary Infections During The Dry-Period Or Clinical Mastitis During Early Lactation: A Protocol For A Systematic Review, Jan M. Sargeant, Charlotte Winder, Annette M. O'Connor, Hannah Wood, Julie M. Glanville, David F. Kelton, Stephen LeBlanc, Todd Duffield 2018 Universty of Guelph

The Efficacy Of Antibiotic Treatments In Dairy Cows At Dry-Off To Prevent New Intramammary Infections During The Dry-Period Or Clinical Mastitis During Early Lactation: A Protocol For A Systematic Review, Jan M. Sargeant, Charlotte Winder, Annette M. O'Connor, Hannah Wood, Julie M. Glanville, David F. Kelton, Stephen Leblanc, Todd Duffield

Veterinary Diagnostic and Production Animal Medicine Reports

Rationale: The majority of antibiotic use in the dairy industry is for the treatment and prevention of intramammary infections (IMI); in the Netherlands, approximately 60 % of all antimicrobial use in dairy is for this purpose, with two-thirds being dry cow therapy (Lam et al., 2012). In the United States, over 90 % of dairy cows receive dry cow therapy after every lactation (USDA-APHIS, 2016), with the goal of treating or preventing IMI during the dry period. These infections are strongly associated with risk of development of clinical mastitis in the first two weeks post-calving, which represents the highest risk period for ...


Intestinal Stem Cells To Advance Drug Development, Precision, And Regenerative Medicine: A Paradigm Shift In Translational Research, Jonathan P. Mochel, Albert E. Jergens, Dawn Kingsbury, Hyun Jung Kim, Martín G. Martín, Karin Allenspach 2018 Iowa State University

Intestinal Stem Cells To Advance Drug Development, Precision, And Regenerative Medicine: A Paradigm Shift In Translational Research, Jonathan P. Mochel, Albert E. Jergens, Dawn Kingsbury, Hyun Jung Kim, Martín G. Martín, Karin Allenspach

Biomedical Sciences Publications

Recent advances in our understanding of the intestinal stem cell niche and the role of key signaling pathways on cell growth and maintenance have allowed the development of fully differentiated epithelial cells in 3D organoids. Stem cell-derived organoids carry significant levels of proteins that are natively expressed in the gut and have important roles in drug transport and metabolism. They are, therefore, particularly relevant to study the gastrointestinal (GI) absorption of oral medications. In addition, organoids have the potential to serve as a robust preclinical model for demonstrating the effectiveness of new drugs more rapidly, with more certainty, and at ...


What Is The Efficacy Of Viral And Bacterial Vaccines In Feedlot Cattle To Reduce Bovine Respiratory Disease (Brd) And Subsequent Antibiotic Use?, Annette M. O'Connor, Chong Wang, Jan M. Sargeant, Brad White, Robert Larson, Bing Wang, Cheryl Waldner, Hannah Wood, Julie M. Glanville 2018 Iowa State University

What Is The Efficacy Of Viral And Bacterial Vaccines In Feedlot Cattle To Reduce Bovine Respiratory Disease (Brd) And Subsequent Antibiotic Use?, Annette M. O'Connor, Chong Wang, Jan M. Sargeant, Brad White, Robert Larson, Bing Wang, Cheryl Waldner, Hannah Wood, Julie M. Glanville

Veterinary Diagnostic and Production Animal Medicine Reports

Bovine respiratory disease complex is the most economically significant disease of feedlot cattle[4]. Putative causal organisms include Mannheimia haemolytica, Pasteurella multocida, Histophilus somni and Mycoplasma bovis, bovine herpesvirus, bovine viral diarrhea virus, bovine respiratory syncytial virus, and parainfluenza type 3 virus[5].

Vaccination against the putative causal organisms is a frequently used approach to aid in the prevention of BRD. With a more significant concern for prudent antibiotic use in the beef industry, it is vital that decision making with regards BRDC management be based on an understanding of the efficacy of vaccination programs and management factors that might ...


Protocol: Non-Antibiotic, Alternative Approaches To The Nursery Phase Of Swine Production: A Scoping Review, Lee V. Wisener, Jan M. Sargeant, Terri O'Sullivan, Annette M. O'Connor 2018 University of Guelph

Protocol: Non-Antibiotic, Alternative Approaches To The Nursery Phase Of Swine Production: A Scoping Review, Lee V. Wisener, Jan M. Sargeant, Terri O'Sullivan, Annette M. O'Connor

Veterinary Diagnostic and Production Animal Medicine Reports

It is widely accepted that antibiotic use drives the development of antibiotic resistance. Hence it is important that swine production uses antibiotics in a judicious manner. In addition, the label claim for livestock antibiotic growth promoters (AGP) of importance to humans has been removed in Canada. In reality, antibiotics have contributed greatly to efficiencies in meat production and animal health. A reduction in the use of growth promoting antibiotics has ramifications for costs of meat production and animal welfare given that sick animals need to be treated, often with antibiotics. Consequences of similar AGP bans in swine production in Europe ...


The Efficacy Of Teat Sealants In Dairy Cows At Dry-Off To Prevent New Intra-Mammary Infections During The Dry-Period Or Clinical Mastitis During Early Lactation: A Protocol For A Systematic Review, Jan M. Sargeant, Charlotte Winder, Annette M. O'Connor, Hannah Wood, Julie M. Glanville, David F. Kelton, Stephen LeBlanc, Todd Duffield 2018 University of Guelph

The Efficacy Of Teat Sealants In Dairy Cows At Dry-Off To Prevent New Intra-Mammary Infections During The Dry-Period Or Clinical Mastitis During Early Lactation: A Protocol For A Systematic Review, Jan M. Sargeant, Charlotte Winder, Annette M. O'Connor, Hannah Wood, Julie M. Glanville, David F. Kelton, Stephen Leblanc, Todd Duffield

Veterinary Diagnostic and Production Animal Medicine Reports

Rationale: The majority of antibiotic use in the dairy industry is for intramammary infections (IMI), with a large portion of this aimed at treating and preventing IMI during the dry period (Lam et al., 2102). During dry off, formation of the teat-canal keratin plug plays an important role in susceptibility to IMI (Huxley et al., 2002), but there is wide variation between cows on time to complete closure of the teat-canal, or indeed if closure occurs at all (Dingwell et al., 2003). In heifers, pre-partum IMI is an important risk factor for the development of clinical mastitis in early lactation ...


Protocol For A Scoping Review Of Influenza A Viruses Infecting Swine Or Directly Related To Swine, Sheila Keay, Zvonimir Poljak, Annette O'Connor, Robert Friendship, Terri O'Sullivan, Jan Sargeant 2018 University of Guelph

Protocol For A Scoping Review Of Influenza A Viruses Infecting Swine Or Directly Related To Swine, Sheila Keay, Zvonimir Poljak, Annette O'Connor, Robert Friendship, Terri O'Sullivan, Jan Sargeant

Veterinary Diagnostic and Production Animal Medicine Reports

Influenza A viruses are endemic in swine populations, a global zoonotic concern, and associated with economically significant disease in food animal production. Global partnerships (Star-IDAZ 2014, USDA 2014, European Food Safety Authority 2015, WHO 2017) have conducted gap analyses on Animal Influenza Research and set research agendas for various species. To date, however, an explicit inventory of the broad areas of accumulated research on Influenza A viruses in swine or directly related to swine (IAV-S), constructed in compliance with syntheses standards for literature mapping (Arksey and O’Malley 2005), is not available.

In particular, a baseline descriptive categorization of the ...


Network On Veterinary Medicines Initiated By The European Federation For Pharmaceutical Sciences, J. P. Mochel, E. Tyden, K. Hellmann, J. C. Vendrig, S. Senel, L. Dencker, R. T. Cristina, H. Linden, I. Schmerold 2017 Iowa State University

Network On Veterinary Medicines Initiated By The European Federation For Pharmaceutical Sciences, J. P. Mochel, E. Tyden, K. Hellmann, J. C. Vendrig, S. Senel, L. Dencker, R. T. Cristina, H. Linden, I. Schmerold

Biomedical Sciences Publications

The European Federation for Pharmaceutical Sciences (EUFEPS) was founded 25 years ago by more than 20 national pharmaceutical societies and faculty members. As a pan- European organisation it brings together pharmaceutical societies as well as academic, industrial, and regulatory scientists engaged in drug research and development, drug regulation, and education of professionals working in these fields.

EUFEPS represents pharmaceutical sciences in Europe and is recognised as such by both the European Commission and the European Medicines Agency. EUFEPS cooperates with the European Federation of Pharmaceutical Industries and other European organisations and maintains global connections with agencies such as the US ...


Lead Poisoning In Bald Eagles Admitted To Wildlife Rehabilitation Facilities In Iowa, 2004–2014, Taylor Yaw, Kay Neumann, Linette Bernard, Jodeane Cancilla, Terese Evans, Adam Martin-Schwarze, Bianca Zaffarano 2017 Iowa State University

Lead Poisoning In Bald Eagles Admitted To Wildlife Rehabilitation Facilities In Iowa, 2004–2014, Taylor Yaw, Kay Neumann, Linette Bernard, Jodeane Cancilla, Terese Evans, Adam Martin-Schwarze, Bianca Zaffarano

Veterinary Clinical Sciences Publications

Eleven years (2004–2014) of bald eagle Haliaeetus leucocephalus data from four independent, state and federally permitted wildlife rehabilitators in Iowa were assessed for the prevalence of elevated lead levels in blood or tissue samples. The relationship between blood lead concentrations and recorded information (age, season, radiographs, and clinical outcome) was investigated. Adult birds had higher blood lead concentrations than immature and juvenile birds. Highest blood lead levels were found during October–January. Bald eagles with positive radiographs for metallic opacities in the digestive tract had higher blood and tissue lead concentrations than those with negative results or those on ...


Spotlight On The Perioperative Use Of Maropitant Citrate, Bonnie L. Hay Kraus 2017 Iowa State University

Spotlight On The Perioperative Use Of Maropitant Citrate, Bonnie L. Hay Kraus

Veterinary Clinical Sciences Publications

Neurokinin-1 (NK-1) receptors are present in both the central nervous system and peripheral tissues. Substance P (SP) is the major ligand and is involved in multiple processes including pain transmission, vasodilation, modulation of the inflammatory response, as well as the sensory neuronal transmission involved in stress, anxiety, and emesis. The involvement of NK-1 and SP in the vomiting reflex has led to the development of NK-1 antagonists to prevent and treat vomiting in human and veterinary medicine. Maropitant is a potent, selective neurokinin (NK-1) receptor antagonist that blocks the pharmacologic action of SP in the central nervous system. Maropitant is ...


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