Hello, Summarians!

We rarely have studies about any issue regarding action and drugs, so I thought I would include this article. Also, a good study about timing and neutering. These are variables, unlike genetics, that we can control.

Please give me feedback on ways I can make it more useful to you.

If it is valuable to you please consider sending it on to a friend 😄 

Xanax and Mares Milk

Alprazolam, a benzodiazepine, is used to facilitate bonding in aggressive or anxious postpartum mares, yet data on its transfer into milk and subsequent absorption by nursing foals have been lacking. This study aimed to measure alprazolam levels in the serum and milk of mares to calculate the milk-to-serum ratio and to determine serum concentrations in nursing foals to estimate the extent of absorption. Seven healthy postpartum mares and their foals participated in a prospective observational study where mares received oral alprazolam at a dose of 0.04 mg/kg every 12 hours for six days. Blood and milk samples were collected on days 3 to 6, just before the next dose, to calculate milk-to-serum ratios and assess foal absorption. A validated liquid chromatography-tandem mass spectrometry assay measured alprazolam and its metabolite α-hydroxyalprazolam. 

The results indicated no significant differences in concentrations of alprazolam or its metabolite in mare serum, milk, or foal serum over time. Milk-to-serum ratios were variable but generally similar to or higher than those reported in humans, with a median of 0.64 and a range of 0.42 to 3.0. The relative foal dose, based on 12-hour concentrations, was less than 10% in all foals and in 96% of total samples. Foal serum concentrations were approximately 6.6% ± 4.1% of the mare serum concentrations at corresponding time points. The study concluded that although milk-to-serum ratios of alprazolam in mares are variable, the low foal serum concentrations and relative foal dose suggest that alprazolam is safe for use in mares with nursing foals. 

^{_{Distribution of Alprazolam into the Milk of Lactating Mares and Subsequent Absorption by Nursing Foals Camilla Quattrini1; Heather Knych2, DVM, PhD, DACVCP; Gary Magdesian2, DVM, DACVIM (LAIM), DACVECC, DACVCP 1University of Georgia, Athens, GA, USA; 2University of California-Davis, Davis, CA, USA https://onlinelibrary.wiley.com/doi/10.1111/jvim.1717}}

Bottom line — Relative dose is less than 10%.

Immunotherapy and Cancer in Dogs.

In veterinary oncology, particularly in dogs, immunotherapeutic approaches are under investigation, offering potential benefits for both animal and human health due to similarities in cancer biology across species. Targeted monoclonal antibodies (MoAbs) like anti-CD20 agents (e.g., 4E1-7-B and 1E4-cIgGB) have been developed to treat canine B-cell lymphoma, mimicking the success of rituximab in human lymphoma treatment. Immune checkpoint inhibitors (ICIs), which block inhibitory pathways that prevent T-cell activation, are also being studied. Canine-specific ICIs targeting PD-1 and PD-L1, such as c4G12 and ca-4F12-E6, have shown promise in treating cancers like malignant melanoma, and Gilvetmab has been conditionally approved for certain mast cell tumors and melanomas in dogs. 

Cancer vaccines stimulate the immune system to attack cancer cells by presenting tumor-specific antigens. The Oncept vaccine, targeting human tyrosinase, is used for canine oral malignant melanoma. Preventative vaccines targeting shared neoantigens are also being researched to reduce cancer incidence in dogs. Adoptive cell therapy involves extracting a patient's immune cells, enhancing or modifying them outside the body, and reinfusing them to fight cancer. CAR-T cell therapy, where T cells are genetically engineered to target specific cancer antigens, has been tested in dogs with lymphoma and solid tumors, though challenges remain in ensuring the persistence and efficacy of these modified cells. 

Cytokine therapies utilize proteins like interleukin-2 (IL-2) and interleukin-12 (IL-12) to boost immune responses but often cause systemic side effects. New approaches aim to localize cytokine activity within the tumor microenvironment (TME) to enhance antitumor effects while minimizing toxicity. Engineered cytokines that bind to components within the TME have shown promise in early studies. 

The TME poses significant challenges to immunotherapy due to its protective structure and immunosuppressive cells that shield cancer cells from immune attack. Strategies that alter the TME, such as reprogramming macrophages from a tumor-promoting (M2) to a tumor-fighting (M1) phenotype, are being investigated to improve immunotherapeutic outcomes. 

Comparative oncology, which studies cancer across different species, provides valuable insights that can accelerate the development of new treatments. Research involving pet dogs with naturally occurring cancers can inform human cancer therapies and vice versa, benefiting both veterinary and human medicine. 

In conclusion, while immunotherapy holds great promise for cancer treatment, challenges remain, including variable response rates, unpredictable efficacy, and potential side effects like autoimmune reactions. A deeper understanding of the immune system's interaction with cancer, particularly the roles of various immune cells within the TME, is essential. Collaborative and comparative research approaches are crucial for advancing effective immunotherapeutic strategies to combat cancer in both animals and humans. 

Hampel, J. M., Cheuk, N., Barbosa, M. M. P., & Fan, T. M. (2024). The promise of immunotherapeutic strategies to advance cancer treatment in pet dogs. Journal of the American Veterinary Medical Association https://doi.org/10.2460/javma.24.08.0532 

Bottom line — Early results support these therapies as options

Neutering and Cruciate Rupture in Dogs

Non-contact cruciate ligament rupture (CR) is a common degenerative condition in dogs, particularly affecting Labrador Retrievers, with a prevalence of 5.79% in the breed. CR is a complex genetic disease with high heritability, influenced by both genetic and environmental factors. This study aimed to identify environmental risk factors contributing to CR in Labrador Retrievers by evaluating dogs whose clinical phenotypes did not match their genetic risk assessments—specifically, dogs that developed CR despite low genetic risk or remained healthy despite high genetic risk. 

Researchers investigated several environmental factors: neuter status, age at neutering, withers height, weight, body mass index (BMI), and athletic activity. They hypothesized that overall neutering, neutering before 12 months of age, increased BMI, and higher athletic activity would increase CR risk. The study found that neutering before 12 months of age significantly increased the risk of developing CR in Labrador Retrievers. However, overall neuter status, neutering before 6 months of age, BMI, weight, height, sex, and athletic activity did not significantly influence CR risk. 

These findings suggest that early neutering is a modifiable environmental risk factor for CR in Labrador Retrievers. The lack of association with other factors like BMI and athletic activity indicates that, in this breed, genetics play a more substantial role in CR development than previously understood environmental factors. The study emphasizes the importance of considering both genetic predisposition and the timing of neutering when assessing CR risk. This information can help veterinarians and owners make informed decisions to potentially reduce the incidence of CR, particularly in dogs with a high genetic risk. 

 DeForge, T. L., Momen, M., Conidi, G., Muir, P., & Sample, S. J. (2024). Age of neutering contributes to risk of cruciate ligament rupture in Labrador Retrievers. Journal of the American Veterinary Medical Association https://doi.org/10.2460/javma.24.06.0406 

Bottom line — We should wait until they are 12 months.

Just putting things in perspective …