The Pathogen Inactivation of Platelets: Studies of the Possible Mechanisms of the Platelet Dysfunction Seen Following Photochemical Treatment.
Notice bibliographique
Résumé
Abstract Background: The platelet mitochondrial genome has many similarities to bacterial and viral genomes. These include the lack of DNA redundancy, the lack of introns, no protective histone proteins, and inefficient DNA repair mechanisms; all of which are important characteristics that likely contribute to the increased rate of mutations occurring with mitochondrial DNA (mtDNA) compared to that seen with nuclear genomic DNA. Recent studies have shown that the use of pathogen inactivation involving UVA phototherapy using the combination of ultraviolet A (UVA) light and either the photoactive psoralen 4′-aminomethyltrioxsalen hydrocholoride (AMT/UVA, known to induce cross-linking of DNA) or the B-vitamin riboflavin (RF/UVA, known to produce the oxidized guanine moiety 8-OH-dG) are effective approaches to reduce and/or inactivate the bacterial and viral contaminants often present in human blood products. Such treatments however have been shown to be associated with impaired in vivo platelet recovery, survival and hemostatic function. Methods and Results: In the current study, rabbit and human platelets were treated with the two photochemical pathogen inactivation methods, (AMT/UVA or RF/UVA), using various UVA exposure, and the resultant platelets compared to control platelets with regard to their in vivo recovery, survival, and hemostatic function, as well as evaluating evidence of damage to platelet mtDNA. Rabbit platelets treated with UVA (1 to 5 joules/cm2) alone, RF alone, or AMT alone, showed minimal or no effect on in vivo platelet function; without evidence of damage to mtDNA. In contrast, the photochemical treatment of rabbit platelets with either AMT/UVA or RF/UVA showed a UVA-dose-dependent effect on in vivo platelet function as well as on mtDNA damage. Platelets treated with AMT/UVA(1 to 5 joules/cm2) revealed a 10–30% UVA-dose-dependent reduction in platelet recovery, survival, and hemostatic function, as well as a widespread but a non-specific effect upon platelet mtDNA structure. The treatment of rabbit platelets with RF/UVA(1 to 5 joules/cm2) showed considerably greater impact on platelet recovery, survival, and hemostatic function than that seen with AMT/UVA, at equivalent UVA doses. This was associated with a reproducible impairment of the amplification of a 3.8kb fragment within the platelet mtDNA genome. This mtDNA fragment is specifically associated with the coding for the NADH dehydrogenase subunit 1. A threshold dose of 1.0 joule/cm2 was noted for RF/UVA treatment, below which damage to mtDNA was found to be UVA-dose-dependent. Using HPLC to determine the concentration of 8-OH-dG within photochemically treated human platelets resulted in the demonstration of a UVA-dose-dependent increase of 8-OH-dG production for RF/UVA treated platelets. Control (no treatment), UVA alone, or AMT/UVA treated platelets produced no increase in 8-OHdG levels, even at UVA doses of 5 joules/cm2. Conclusions: These results indicate that the reproducible focal damage of platelet mtDNA by RF/UVA may have a considerably greater effect upon platelet in vivo circulatory and hemostatic functions than does the introduction of random mtDNA cross-linking produced by AMT/UVA treatment, possibly because of the discrete reproducible defect caused by the RF/UVA on the platelet mtDNA. These data nonetheless support the hypothesis that platelet mtDNA damage produced by pathogen inactivation methodology is associated with and may affect subsequent in vivo platelet function following platelet transfusion to a recipient.
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 | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 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 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 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 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 ».