A novel nanobiotechnological oxygen and carbon dioxide carrier with enhanced antioxidant properties: polyhemoglobin -superoxide dismutase-catalase-carbonic anhydrase
Pourquoi ce travail est dans la base
Une base qui oublie comment elle a trouvé un travail ne peut pas être vérifiée. Voici les voies qui ont admis celui-ci.
Notice bibliographique
Résumé
ABSTRACTIntroduction: The shortage of donor blood gives rise to demand for blood substitute. The most successful blood substitute, polymerized hemoglobin (PolyHb), has been approved for routine clinical use in South African and Russia. However, PolyHb is only an oxygen carrier but not a complete red blood cells (RBCs) substitute. RBCs have three main functions: 1) Oxygen transport; 2) anti-oxidant enzyme activities; 3) Carbonic dioxide transport. Thus, transfusion of PolyHb in severe ischemia conditions could give rise to ischemia reperfusion injuries. This is due to the lack of anti-oxidant enzyme activities in the PolyHb. In addition, recently researches show that elevation of tissue pCO2 in severe hemorrhagic shock is related to increase in mortality. This suggests that CO2 transport is also a vital function of any RBC substitutes. This thesis presents the design and detailed evaluation of a novel blood substitute, Polyhemoglobin-superoxide dismutase- catalase- carbonic anhydrase (Poly-[Hb-SOD-CAT-CA]). This has all of the three main functions of RBC.Method: The enzyme for CO2 transport, carbonic anhydrase (CA) and the anti-oxidant enzymes, superoxide dismutase (SOD) and catalase (CAT) are crosslinked together with Hb by nanobiotechnology to form Poly-[Hb-SOD-CAT-CA]. After optimizing the crosslink procedure, detailed in vitro and in vivo analysis has been carried out to fully evaluate this new complex. The in vitro studies include the test of enzymes activity and kinetics, molecular distribution, temperature stability, storage stability, P50 as well as screening test using complement activation. Two lethal shock models are used. One is 60 min shock and the other is outside the 60 min safety window, 90 min shock. These in vivo studies evaluate the effects of Poly-[Hb-SOD-CAT-CA] on maintaining mean artery pressure (MAP), lowering of the elevated tissue pCO2 as well as recovery of ST-elevation. In the 90 min shock model, the effects on biochemistry and histology of the heart, intestine, kidney and liver have also been analyzed. Result: After crosslinking, Poly-[Hb-SOD-CAT-CA] retains significant enzymes activity and proper molecular distribution. The MetHb decreases to an acceptable content after optimization. The sample could be kept for a long time (128days) in the solution form at 4℃ and -80℃ and still maintain its molecular distribution and main part of enzyme activities. Lyophilization extends the storage time to 320 days and these freeze-dried samples show good temperature stability even for 30 minutes to 3 hours at the pasteurization temperature of 65℃. The oxygen carrying ability of this blood substitute is maintained before and after storage. In vitro screening test shows that Poly-[Hb-SOD-CAT-CA] does not cause complement activation.Studies on the 60 min shock model shows that Poly-[Hb-SOD-CAT-CA] could maintain the MAP at 80mmHg and also facilitate the recovery of the ST-elevation. Unlike PolyHb, Poly-[Hb-SOD-CAT-CA] also effectively lowers the elevated tissue pCO2. When extending beyond the 60 min safety window shock model to a more severe 90 min one, the results are even more striking. Here it is significantly more efficient than blood reinfusion in the lowering of tissue pCO2 and recovery of ST-elevation. In addition histological analysis on for tissue injuries and biochemistry shows that Poly-[Hb-SOD-CAT-CA] could protect the heart, liver, kidney and intestine from ischemia reperfusion injuries. Summary: This thesis firstly presents the design of a novel nanobiotechnological O2 and CO2 carrier with enhanced antioxidant enzyme activities. Detailed in vitro analysis together with in vivo evaluation suggests that this new complex is a promising novel approach towards a blood substitute deserving further investigation.
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.
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,001 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
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 découle