0133 Feasibility and safety of nitric oxide releasing solution as a treatment for bovine mastitis
Bibliographic record
Abstract
Nitric oxide releasing solution (NORS) is a liquid formulation that releases nitric oxide (NO). NO is a broad, nonspecies-specific nonmicrobial nanomolecule, endogenously produced during the innate response in mammals. The objective of this study was to explore the feasibility of NORS as a potential treatment for bovine mastitis (BM). Two common pathogens found in BM (106 CFU/mL of Escherichia coli and Staphylococcus aureus) were added to raw milk from healthy cows, as an in vitro model, to determine the antimicrobial efficacy of NORS at different concentrations (100–400 mM) and at two different NORS:milk ratios (2:1 and 1:1). Next, 10 ex vivo samples of milk from dairy cows presenting with clinical mastitis were obtained and treated with NORS to confirm efficacy. A dose escalating safety study was then performed using three dairy cows, where 40 mL of increasing concentrations of NORS (50–400 mM) were infused into the teat. Nitrite and methemoglobin levels were measured 5, 30, and 460 min posttreatment and nitrites in milk were measured 8 and 24 h posttreatment. Nitrite was measured by chemiluminescence, while methemoglobin was measured using a CO-Oximeter. Results show that NORS could eradicate, in vitro, both bacteria, and was dilution and time dependent. In the 2:1 ratio, NORS significantly (P < 0.05) reduced bacterial concentration in milk both in vitro and ex vivo within 2 min, and had no detectable bacteria after 5 min of exposure. In the 1:1 ratio, a significant bacterial load reduction (P < 0.01) occurred within 10 min and no detectable bacteria within 20 to 30 min. In the safety study we found an increase in blood nitrites (P < 0.05) within 5 min of the NORS treatment at all concentrations. After 8 h, the blood values at all concentrations returned to baseline (P = 0.27). Blood methemoglobin changes were nominally increased in the 5 and 30 min samples post 400 mM NORS and no detectable change was seen after 8 h. Eight hours posttreatment, before the evening milking, milk nitrites were 18 times higher than baseline, while 24 h posttreatment nitrites returned to baseline level (P = 0.36). NORS was found to eradicate bacteria in milk and, clinically, the treatment was well tolerated. This suggests that NORS has a potential to be a safe and effective nonmicrobial treatment for BM and may allow salable milk during antimicrobial treatment of mastitis. Further, it would provide an alternative to antibiotics, thus contributing to the reduction of antibiotic drug resistance. Further studies are justified.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".