Can We Grow Hoof Wall Faster?

Hello, Summarians

Transdermal CO2? Wow! That is thinking outside the box… Also, an interesting study about the genetic basis for IBD. There are even current meds that might work to downregulate the responsible genes. This could be huge …

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Hoof Growth with Transdermal CO2 in Horses.

This study explored the effects of medical-grade transdermal CO2 on hoof growth in healthy horses over a 5-week treatment period. Hoof growth rates in horses are variable and can be influenced by factors like nutrition, activity level, and environmental conditions. Delayed or slow hoof growth can lead to significant clinical challenges, particularly in horses with thin soles or increased sensitivity. Various commercial products, including nutritional supplements and treatments like biotin, have shown mixed results, and limited research exists on other interventions. 

The study builds on anecdotal reports suggesting transdermal CO2 may enhance hoof growth, based on its known effects on wound healing in human and animal models through improved oxygen delivery and blood flow due to the Bohr effect. The researchers hypothesized that CO2 treatment would accelerate hoof growth. The study employed a crossover design, treating the horses' forelimbs with CO2 three times a week while controlling for variables like nutrition and seasonal factors. Hoof growth was measured using digital calipers, and efforts were made to minimize human error. 

While the study found that CO2 may accelerate hoof growth, limitations such as the small sample size, short study duration, and variability in measurements were noted. Human error in measuring hoof growth and inconsistencies in treatment effects across hooves suggest the need for further research. Despite some promising results, the findings should be interpreted cautiously, and more studies are needed to confirm the reproducibility and broader applicability of CO2 treatment in horses, especially those with poor hoof quality. 

Rudnick, M. J., Stewart, H. L., Burleson, M. D., & Levine, D. G. (2024). Transdermal carbon dioxide may accelerate hoof growth in healthy, sound horses in a short-term, randomized, controlled clinical trial. American Journal of Veterinary Research https://doi.org/10.2460/ajvr.24.06.0161 

Bottom line — This treatment shows promising results.

Predicting Prognosis in Critical Foals

The endothelial glycocalyx (EG) is a gel-like layer covering the vascular endothelial cells, playing a crucial role in regulating vascular permeability, providing anticoagulant effects, and maintaining vascular integrity. Syndecan-1 (SDC-1) and heparan sulfate (HS) are key components of the EG, and its degradation is associated with various disease conditions such as sepsis, hypoxia, inflammation, and shock. Elevated levels of certain biomarkers, such as angiopoietin-2 (ANG-2), atrial natriuretic peptide (ANP), and aldosterone (ALD), are linked to EG damage. 

In critically ill newborn foals, sepsis is a leading cause of morbidity and mortality, with septic foals showing significant disturbances in hemodynamic, glucose, acid-base, and fluid balance. These alterations could predispose them to EG degradation, contributing to the clinical signs of sepsis. The renin-angiotensin-aldosterone system (RAAS), activated in response to stress in critically ill foals, may also contribute to endothelial injury. Elevated ALD levels in septic foals have been noted, potentially accelerating EG degradation. 

This study investigated the concentrations of EG degradation markers (SDC-1, HS, ANG-2, and ANP) in critically ill foals during hospitalization. The study aimed to explore their association with disease severity and outcomes, hypothesizing that higher levels of these markers would be found in septic and non-surviving foals. The findings confirmed that EG degradation, evidenced by elevated concentrations of SDC-1, HS, and ANG-2, was associated with disease severity and mortality in hospitalized foals. High levels of ANG-2, ANP, and HS were particularly associated with non-survival. 

The study's results align with findings in human sepsis cases, where elevated SDC-1 and HS concentrations indicate EG damage. Inflammatory responses, including the release of cytokines and enzymes like heparanase, exacerbate EG degradation, leading to increased vascular permeability and microvascular dysfunction. ANG-2 and ANP, both elevated in septic foals, play crucial roles in promoting EG degradation and increasing vascular permeability. Similarly, ALD, a component of RAAS, promotes endothelial damage by increasing immune cell adhesion, which further contributes to EG degradation. 

Although the study provided valuable insights into the association between EG degradation and disease severity in foals, it had limitations. Unrecorded factors such as hydration, renal function, and fluid therapy could have influenced the results. Nonetheless, the study highlights the importance of EG integrity in critically ill foals, suggesting that elevated EG degradation markers can be useful in assessing disease severity and prognosis in hospitalized foals.

Gomez DE, Kamr A, Gilsenan WF, et al. Endothelial glycocalyx degradation in critically ill foals. J Vet Intern Med. 2024; 1-10. doi:10.1111/jvim.17196 

Bottom line — Test Shows Promise in Predicting Prognosis in Foals

Genetic Basis for IBD?

The research highlights the complexity of autoimmune and inflammatory diseases, which affect nearly 5% of the population. These diseases include Crohn’s disease, ulcerative colitis, psoriasis, and lupus, all of which require improved therapies. Despite significant advances in genetics, drug development for these diseases has a high failure rate, with only 10% of drugs in clinical development becoming approved treatments. This failure is largely due to the lack of understanding of disease mechanisms. 

Genetics offers a promising pathway to address this challenge by linking hundreds of loci to immune-mediated diseases. Drugs targeting genetically implicated pathways tend to have a higher efficacy. However, understanding how genetic variants, particularly non-coding ones, drive disease mechanisms remains a significant obstacle. Animal models have been helpful for coding variants, but most risk variants lie in non-coding regions, complicating efforts to resolve their effects on gene regulation. 

One example is a region on chromosome 21q22, which is associated with multiple inflammatory diseases. Researchers hypothesize that this region contains a monocyte/macrophage-specific enhancer involved in immune responses. By using chromatin immunoprecipitation (ChIP) and gene expression analyses, the study identified ETS2, a gene regulated by this enhancer, as central to inflammatory processes in macrophages. Deletion of the enhancer significantly reduced ETS2 expression and impaired macrophage functions such as cytokine production, phagocytosis, and reactive oxygen species (ROS) production. 

Further analysis revealed that ETS2 regulates numerous inflammatory genes and pathways, including cytokine production, macrophage activation, and ROS production. These findings position ETS2 as a central regulator of macrophage inflammation. Overexpression of ETS2 in macrophages induced a state similar to that seen in diseases like Crohn’s disease, suggesting its key role in disease pathogenesis. 

Importantly, the study also explored therapeutic opportunities by targeting the ETS2 pathway. MEK inhibitors, which regulate ETS-family transcription factors, were found to mimic the effects of disrupting ETS2, suggesting their potential as treatments for inflammatory diseases. In ex vivo experiments with human macrophages and intestinal biopsies, MEK inhibitors showed potent anti-inflammatory effects, reducing cytokine production and inflammatory gene expression. 

In summary, the study identifies ETS2 as a critical regulator of macrophage-driven inflammation and highlights the potential of targeting this pathway in autoimmune and inflammatory diseases. By leveraging genetic insights, the research opens new avenues for developing more effective therapies.

Stankey, C.T., Bourges, C., Haag, L.M. et al. A disease-associated gene desert directs macrophage inflammation through ETS2. Nature 630, 447–456 (2024). https://doi.org/10.1038/s41586-024-07501-1 

Bottom line — Potentially huge implications.

Just putting things in perspective …