Animal Health Research Weekly – 3
Time for announcements We have all been there already: You are in the middle of a heated discussion, with many opinionated parties. Everyone wants to tell their own story, and you have uncle Jim reminding of the time he had that particularly nasty case, while aunt Emma starts with the philosophy lesson on how things should run. In the middle of the storm, you think to yourself “didn’t we discuss this already 1000 times already?” Fact is, noone was there to write it down, and if you ask 3 people in the group you get 7 different versions of what was discussed last time. Now that’s science: everyone write things down. But not everyone can prove that what you wrote down is correct. So every time in a while, someone sits down and tries to get all the strings together and make sense of them. This week, we owe it to Arielle Johnson-Pitt for her wonderful review on the role of inflammation in canine diabetes. And a big thank you also to the ENOVAT for their new guidelines for Antimicrobial use in Canine Acute Diarrhea. Enjoy! Reviews and Guidelines Is Exocrine Pancreatic Inflammation a Hidden Factor in Canine Diabetes? In this review, Arielle Johnson-Pitt et al from THE ROYAL VETERINARY COLLEGE , UK, explore the link between exocrine pancreatic inflammation and canine diabetes mellitus, proposing that exocrine pancreatic inflammation could be an under-recognized cause of β-cell death, contributing to insulin-deficiency diabetes in dogs. Up to 30% of diabetic dogs show evidence of pancreatitis post-mortem, yet current diagnostics for pancreatitis remain imprecise. The review examines the limitations of current treatments and highlights the need for improved diagnostic and therapeutic strategies that address both pancreatitis and diabetes more effectively in canine patients. Johnson-Pitt A, Catchpole B, Davison LJ. Exocrine pancreatic inflammation in canine diabetes mellitus – an active offender?. The Veterinary Journal, 2024, 106241, ISSN 1090-0233, https://doi.org/10.1016/j.tvjl.2024.106241. ENOVAT Guidelines for Antimicrobial Use in Canine Acute Diarrhea The European Network for Optimization of Veterinary Antimicrobial Therapy (ENOVAT) provides evidence-based guidelines for treating canine acute diarrhea (CAD). Developed by a multidisciplinary panel using the GRADE framework, the guidelines include four strong recommendations and three conditional ones based on varying levels of evidence. The guidelines emphasize judicious antimicrobial use and incorporate input from veterinarians and dog owners. ENOVAT encourages national and regional adaptations to ensure practical, evidence-based approaches for managing acute diarrhea in dogs. L.R. Jessen, M. Werner, D. Singleton, C. Prior, F. Foroutan, A.A. Ferran, C. Arenas, C. R. Bjørnvad, E. Lavy, F. Allerton, K. Allensbach, L. Guardabassi, S. Unterer, T. Bodnárová, U. Windahl, M.L. Brennan, J.S. Weese, K. Scahill. European Network for Optimization of Veterinary Antimicrobial Therapy (ENOVAT) guidelines for antimicrobial use in canine acute diarrhoea. The Veterinary Journal. Volume 307, 2024, 106208, ISSN 1090-0233, https://doi.org/10.1016/j.tvjl.2024.106208. Dog Research Delayed Heartworm Microfilarial Reduction in Dogs After Advocate™ Treatment This study from Power and Šlapeta from the University of Sydney, Australia, examines two cases of canine heartworm (Dirofilaria immitis) in Australia, where dogs showed delayed reductions in microfilariae after treatment with Advocate™ (imidacloprid and moxidectin). Despite claims of rigorous prevention, both dogs exhibited less than 40% microfilariae reduction after seven days, a phenomenon typically associated with macrocyclic lactone (ML) resistance. However, genetic testing indicated no ML-resistant mutations. The findings suggest that while these dogs displayed poor phenotypic response to treatment, their heartworm genotypes remain susceptible, raising questions about potential factors influencing treatment efficacy outside the USA. Power RI, Šlapeta J. Delayed canine heartworm (Dirofilaria immitis) microfilarial reduction following Advocate™ for dogs (imidacloprid, moxidectin) treatment. The Veterinary Journal, Volume 307, 2024, 106209, ISSN 1090-0233, https://doi.org/10.1016/j.tvjl.2024.106209. Pharmacokinetics of Gentamicin-Impregnated Collagen Sponges in Dogs In this study, Tri Bhawono Dadi et al, from the Ghent University, Belgium, investigated the pharmacokinetics of gentamicin-impregnated collagen sponges (GICS) implanted subcutaneously in six healthy dogs. Local gentamicin concentrations peaked within 0.5 to 1 hour post-implantation, providing high antibiotic levels for bacterial elimination. Systemic gentamicin levels peaked at 1.2 hours but dropped below therapeutic levels within six hours. The study shows that GICS provides rapid and high local antibiotic concentrations, potentially effective against resistant bacteria, although wound hydration may influence release rates. T. Bhawono Dadi, N. Devriendt, M. Cherlet, M. Devreese, I. Polis, H. de Rooster. Pharmacokinetic study of local and systemic gentamicin concentrations after subcutaneous implantation of a gentamicin-impregnated collagen sponge in dogs,. The Veterinary Journal, Volume 307, 2024, 106201, ISSN 1090-0233, https://doi.org/10.1016/j.tvjl.2024.106201. Intranasal Dexmedetomidine Alone or with Ketamine or Midazolam for Sedating Dogs Majid Jafarbeglou et al from the Lebanese University. Lebanon, compared the sedative effects of intranasal dexmedetomidine (Dex) alone or combined with midazolam (DexM) or ketamine (DexK) in healthy dogs. The results showed that DexK provided the fastest onset of sedation, while Dex alone was better tolerated with fewer adverse effects. DexM was less effective, with some dogs failing to reach adequate sedation and experiencing paradoxical excitement. Dex and DexK reached peak sedation faster and more consistently than DexM, making them more suitable for sedation in dogs. Jafarbeglou M, Marjani M, Bakhshi-Khanghah R, Paryani M, Oghbaei M. Intranasal atomized dexmedetomidine alone or in combination with ketamine or midazolam to sedate healthy dogs. The Veterinary Journal, Volume 307, 2024, 106224, ISSN 1090-0233, https://doi.org/10.1016/j.tvjl.2024.106224. Montelukast Pharmacokinetics in Dogs: A Preliminary Study Under Fasted and Fed Conditions This preliminary study from Charbel Fadel et al from the Università di Pisa, Italy, explores the pharmacokinetics of montelukast (MTK), a cysteinyl leukotriene receptor antagonist, in six dogs following a single oral dose under fasted and fed conditions. The results showed no significant differences between the two states, with the drug reaching peak concentrations in about 4 hours and having a half-life of approximately 8 hours. The findings suggest that further research is needed to determine the appropriate dosing and efficacy of MTK in dogs, particularly for its off-label use in treating atopic dermatitis. Fadel C, Łebkowska-Wieruszewska B, Lisowski A, Serih F, Poapolathep A, Giorgi A. Exploring montelukast in dogs: A preliminary pharmacokinetic study following oral administration under fasted and fed conditions. The Veterinary
Animal Health Research Weekly – 2
Is this all cause and effect? While putting together this week’s newsletter on Animal Health Research I couldn’t help but notice that a vast majority of the articles from the past week were on canine topics, and specifically infectives-related topics. Such a skewed view would be quite unusual in other branches of science, but here? Are there factors driving it? And what are the consequences? I couldn’t get these questions out of my head, so I researched what is the split of market share in veterinary medicine by indication category, and the results were quite interesting: Now, if we look at the order of the different indications by percentage, we see that infectives are dominating the chart. Astonishingly, Oncology is coming in second place, but this category is quite underrepresented in academic publications. Is most of the research in Oncology simply done in Pharma, and therefore not published? And how much of the focus on the individual areas is fueled by academic work? With these thoughts, I will leave you to this week’s new articles Yours, Infectives Deltamethrin Collars Reduce Leishmaniasis Risk in Infected Dogs Paes de Barros Cortez et al. from the USP – Universidade de São Paulo, Brasil investigated the effectiveness of using 4% deltamethrin-impregnated collars on seropositive dogs to control visceral leishmaniasis (VL) in endemic areas of Brazil. Comparing two districts, one using conventional methods (including euthanasia) and the other employing strategic collaring, the study found that dogs with the collars had up to four times lower risk of infection. This approach, targeting only seropositive dogs, offers a promising and less controversial alternative to mass collaring, significantly reducing costs and improving VL control in endemic regions. L. R. Paes de Barros Cortez, J. E. Tolezano, R. M. Hiramoto, M. R. de Paula e Silva, J. E. F. Passos, S. H. Antônio, V. M. Camprigher, M. J. V. Vendramini Cuoghi, G. Vioti, F. Ferreira, R. M. Soares. Strategic use of 4 % deltamethrin impregnated-collar in seropositive dogs reduces the incidence of seroreactivity to visceral leishmaniasis in dogs from endemic areas. Research in Veterinary Science, Volume 179, 2024, 105397, ISSN 0034-5288, https://doi.org/10.1016/j.rvsc.2024.105397. Genomic Study of Penicillin and Rifampin-Resistant Bacterial Strains in Dog Skin Infections Araújo et al. from the Universidade Federal de Minas Gerais, Brasil, analyzed two strains of Corynebacterium rouxii, a recently identified bacterium, isolated from skin infections in dogs. The strains were found to be resistant to penicillin and rifampin. Through genome sequencing and molecular analysis, researchers identified several antimicrobial resistance genes and virulence factors. The findings provide insights into the genetic makeup and potential risks associated with this little-studied bacterium, emphasizing the need for ongoing monitoring of its resistance and virulence traits, which could have broader implications for both animal and human health. M. R. B. Araújo, F. D. Prates, M. V. C. Viana, L. S. Santos, A. L. Mattos-Guaraldi, C. H. Camargo, C. T. Sacchi, K. R. Campos, V. V. Vieira, M. B. N. Santos, S. Bokermann, J. N. Ramos, V. Azevedo. Genomic analysis of two penicillin- and rifampin-resistant Corynebacterium rouxii strains isolated from cutaneous infections in dogs. Research in Veterinary Science, Volume 179, 2024, 105396, ISSN 0034-5288, https://doi.org/10.1016/j.rvsc.2024.105396. Genome Sequencing of Canine Distemper Virus in Unvaccinated Mongolian Dogs In their latest article, Munkhtsetseg et al. from the University of Life Sciences Zaisan; Mongolia, present the first genetic analysis of Canine Distemper Virus (CDV) in Mongolia, using isolates from three unvaccinated dogs that succumbed to the disease. Genome sequencing revealed that the mixed-breed dogs were infected with a non-recombinant CDV from the Asia-1 lineage, while the Samoyed carried a virus from the Asia-4 lineage. These findings contribute valuable data on the genetic diversity of CDV in Mongolia, providing a foundation for improved control measures and future research in the region. A. Munkhtsetseg, E. Batmagnai, M. Odonchimeg, G. Ganbat, Y. Enkhmandakh, G. Ariunbold, T. Dolgorsuren, R. Odbileg, P. Dulam, B. Tuvshintulga, C. Sugimoto, Y. Sakoda, J. Yamagishi, D. Erdenechimeg. Genome sequencing of canine distemper virus isolates from unvaccinated dogs in Mongolia. The Veterinary Journal, Volume 308, 2024, 106231, ISSN 1090-0233, https://doi.org/10.1016/j.tvjl.2024.106231. Quality Testing of Artemisinin Supplements for Dogs Reveals Inconsistencies Alyssa Berman et al. from the North Carolina State University- College of Veterinary Medicine evaluated the quality of artemisinin supplements marketed for dogs in the U.S. to treat Babesia gibsoni. Using high-performance liquid chromatography, researchers found significant variability in the strength of artemisinin between products and even within the same product. None of the supplements met the quality standards set by the United States Pharmacopeia or International Council for Harmonisation. One product contained no detectable artemisinin, while others had much higher concentrations than stated. The findings underscore the need for rigorous testing of unapproved supplements before clinical use in dogs. Berman, A., Birkenheuer, A., Sorah, E. and Papich, M. (2024), Analysis of US Marketed Artemisinin Supplements for Use in Dogs. J Vet Pharmacol Therap. https://doi.org/10.1111/jvp.13480 Pasteurella multocida Disrupts Blood–Brain Barrier by Weakening Cell Junctions In this study, Lin et al from the Huazhong Agricultural University, China, investigated how Pasteurella multocida, a bacterium known to cause meningitis, disrupts the blood-brain barrier (BBB). Using mouse models and human brain microvascular endothelial cells, researchers found that the infection increases BBB permeability by reducing the expression of tight and adherens junction proteins. The study also identified that the bacteria activate specific signaling pathways, contributing to this disruption. These findings offer new insights into how P. multocida crosses the BBB, advancing our understanding of its role in meningitis in both humans and animals. Lin, L., Bi, H., Yang, J. et al. Pasteurella multocida infection induces blood–brain barrier disruption by decreasing tight junctions and adherens junctions between neighbored brain microvascular endothelial cells. Vet Res 55, 104 (2024). https://doi.org/10.1186/s13567-024-01351-5 Lavender Oil and Otological Gel Show Promise Against Pseudomonas Biofilms in Dog Ear Infections Mourão et al. from the Universidade de Lisboa (University of Lisbon) , Portugal, investigated the effectiveness of lavender oil, an otological gel, and gentamicin in eradicating biofilms produced by Pseudomonas aeruginosa, a common and drug-resistant cause of chronic ear infections
Antibody Libraries in Animal Health Research
In the ever-evolving field of animal health research, antibody libraries have emerged as a pivotal tool. These libraries, essentially collections of antibodies tailored for specific applications, offer researchers a diverse range of antibodies ready for use in various screenings. In this blog post we’ll talk about the significance of antibody libraries, their applications, and the technologies behind their creation. Understanding Antibody Libraries Antibody libraries are designed to maximize diversity, providing researchers with a wide array of antibodies without the need to produce them from scratch. These libraries vary based on their intended application, whether for diagnostics, therapeutics, or research and development tools. The composition and formulation of these libraries are crucial, as they must maintain the antibodies in their correct shape and folding, often including preservation molecules and compounds. Applications in Animal Health Antibody libraries have transformed the way researchers approach diagnostics and therapeutics in animal health. They allow for the development of antibodies against specific targets, such as surface markers on cells, enabling precise diagnostics and treatment options. The libraries also support the creation of antibodies with specific functions, such as blocking immune resistance mechanisms in tumor cells or inhibiting receptor dimerization to prevent signal cascades. Technological Advances in Antibody Libraries The development of antibody libraries has seen significant advancements, with various techniques employed to create these valuable resources. Here are some of the key methods: The Future of Antibody Libraries As antibody libraries continue to evolve, their applications in animal health research expand. These libraries not only aid in diagnostics and therapeutics but also contribute to reducing animal testing by providing alternative methods for drug development. The integration of intracellular tumor-associated antigens and novel targets into these libraries opens new avenues for research and treatment. If you are a researcher in animal health, Lab4Paws offers a comprehensive range of services. With a commitment to ethical practices and collaboration with certified veterinary clinics, Lab4Paws ensures the highest quality samples for your research needs. ————————— At Lab4Paws, we help Animal Health scientists develop therapeutic & diagnostic solutions for companion animals and work to reduce animal testing for human drug development. Searching for CRO services of biospecimens? Contact us at info@statestreetdebating.site or call us at +49 172 460 5978 or +1 617 982 1785
Drug repurposing in Veterinary Science: Past or Future?
As pet ownership continues to rise, the demand for effective veterinary medications grows alongside it. One of the questions often asked by pharmaceutical companies is whether human drugs can be repurposed for use in animals. This approach, while tempting due to its potential cost and time savings, requires careful consideration of numerous factors to ensure the safety and efficacy of the drugs for our furry friends. In this blog post, we’ll explore the key aspects of repurposing human drugs for pets, based on insights from a recent live stream by Lab for POS. What is Drug Repurposing? Drug repurposing involves adapting existing medications, typically developed for humans, for use in animals. While this might seem straightforward, the process is far from simple. Animals have different physiological, metabolic, and genetic makeups compared to humans, which means that a drug that works well in humans might not have the same effect in animals—or could even be harmful. Why is Drug Repurposing Important? The pet medicine market has been expanding rapidly, driven by higher standards of care for pets, increased pet ownership, and longer lifespans for both humans and their animal companions. As a result, the expenditure on veterinary medications is increasing, making the repurposing of human drugs an attractive option for pharmaceutical companies. Market Potential In 2023, the sales of repurposed drugs showed promising growth, with pet drug sales forecasted to increase by 8.3% annually, outpacing the growth of human drug sales. This trend highlights the growing importance of the veterinary pharmaceutical market and the potential benefits of drug repurposing. Key Considerations in Drug Repurposing 1. ADMET Parameters ADMET stands for Absorption, Distribution, Metabolism, Excretion, and Toxicity. These are critical factors in determining how a drug behaves in the body. Different species have varying ADMET profiles, which can significantly impact the drug’s efficacy and safety. For example, the enzymes responsible for drug clearance in dogs differ from those in humans. In dogs, cytochrome P450 enzymes such as CYP3A12 and CYP3A98 play a significant role, whereas in humans, CYP3A4 and CYP3A5 are more prominent. This difference means that a drug metabolized safely in humans might accumulate to toxic levels in dogs, or vice versa. 2. Species-Specific Drug Effects Different animals have unique physiological responses to drugs. A drug used to treat a particular condition in humans might be used for a completely different purpose in animals. For instance, Gabapentin, a drug used to manage pain and seizures in humans, is also used for these purposes in dogs. However, in cats, Gabapentin is primarily used to alleviate anxiety, particularly during veterinary visits. These differences underscore the importance of understanding species-specific drug effects before repurposing a medication. 3. Dosage Variability The appropriate dosage of a drug can vary widely between species, due to differences in metabolism and drug clearance rates. For example, the dosage of Gabapentin for dogs ranges from 50 mg/kg, while for cats, it varies from 5 to 30 mg/kg. This variability highlights the need for precise dosing information to avoid underdosing or overdosing, both of which can have serious consequences. 4. Drug Formulation Differences The formulation of a drug—such as the additives and excipients used—can also affect its safety in animals. Some ingredients safe for human consumption can be toxic to animals. For example, human formulations of Gabapentin often contain xylitol, a sweetener that is highly toxic to dogs and should be avoided in veterinary patients. This emphasizes the need to carefully evaluate and possibly modify drug formulations when repurposing them for pets. 5. Target Expression Levels The expression levels of drug targets can differ significantly between species, leading to variations in drug efficacy. For example, Clopidogrel, an antiplatelet medication used to prevent strokes and heart attacks in humans, targets the P2Y12 receptor on platelets. However, this receptor is expressed at much lower levels in cats and dogs, reducing the drug’s effectiveness in these animals. Understanding these differences is crucial in determining whether a human drug can be successfully repurposed for veterinary use. Conclusion While repurposing human drugs for pets offers significant potential, it requires careful consideration of species-specific differences in drug metabolism, physiology, dosage, formulation, and target expression. Pharmaceutical companies interested in this approach must conduct thorough research and testing to ensure the safety and efficacy of these drugs for animal use. If you’re a pharmaceutical company considering drug repurposing or seeking biospecimens for your research, feel free to contact us at Lab for POS. We are committed to advancing the field of veterinary medicine and helping reduce the reliance on animal testing in both human and animal health research. Thank you for reading, and stay tuned for more insights on the latest developments in veterinary pharmacology!
Best Organ-on-a-Chip Systems of 2024: A Comprehensive Comparison
Organ-on-a-chip technology has revolutionized biomedical research by providing more accurate and reliable models of human and animal physiology. These systems have the potential to replace traditional animal testing, reduce costs, and speed up the development of new therapeutics. In this blog post, we will compare some of the most notable organ-on-a-chip systems available in 2024.
