BLES‐Cath‐2 Intratracheal Administration in an in vivo P. aeruginosa Pneumonia Model
Notice bibliographique
Résumé
Background Increasing patterns of antibiotic resistance, especially in individuals with chronic lung disease, have mandated the development of novel therapies. Host‐defense peptides HDP such as cathelicidin‐2 (CATH‐2), possess excellent antimicrobial activities in vitro however in vivo efficacy has not been well established. Furthermore, in order to enhance in vivo distribution, a novel approach using CATH‐2 combined with bovine lipid extract surfactant (BLES) as a delivery vehicle was utilized. It was hypothesized that CATH‐2/ BLES would be superior to CATH‐2 alone in decreasing bacterial burden and improving physiologic parameters in an in vivo model of Pseudomonas aeruginosa (PA) infection with mechanical ventilation. Methods Adult male Sprague‐Dawley rats were intubated, mechanically ventilated for 30 minutes, followed by an intratracheal inoculum of 8 x 10^8 CFU/mL of PA. One hour following PA administration, rats were randomized to receive an intratracheal administration of either: i) Saline, ii) Air, iii) BLES, iv) Cath‐2, or v) BLES/Cath‐2. Mechanical ventilation continued for three hours during which peak inspiratory pressure (PIP) and arterial blood gases were recorded. At the completion of the ventilation protocol, animals were sacrificed and whole lungs were homogenized and the bacterial burden was assessed by growth analysis of lung homogenates on Cetrimide Agar plates incubated overnight at 37 C. Statistical analysis was performed using a one‐way ANOVA. Results Physiological measurements revealed a significant decline of arterial oxygenation (PaO2) in air and saline control groups. At the three‐hour time point, the BLES/Cath‐2 group had a significantly (p < 0.01) higher PaO2 and compared to the Cath‐2 treated animals. Interestingly, the Cath‐2 group had PIP values at 30 minutes following PA instillation that were significantly higher compared to all groups. Colony growth data demonstrated a significant difference between the Cath‐2 treated animals and the control groups; however there was no difference compared to the BLES/Cath‐2 group. Conclusion Our findings demonstrate that Cath‐2 has excellent anti‐microbial activity against PA in an in vivo model of pneumonia and mechanical ventilation, although significant reduction in lung function was observed. Cath‐2 alone worsens lung function by possibly causing an overwhelming inflammatory response. Furthermore, CATH‐2/ BLES significantly improved physiological parameters compared to Cath‐2 alone. This suggests that the combination of BLES/Cath‐2 allows for both improved lung function and while maintaining antimicrobial activity. Future analysis includes extension of the time points and lavage inflammatory markers. Support or Funding Information Physician Services Inc. and the Canadian Cystic Fibrosis foundation
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| Bibliométrie | 0,001 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,000 | 0,001 |
| Science ouverte | 0,001 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,002 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,001 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».