Resolvins D5 and D1 undergo phase II metabolism by uridine 5'-diphospho-glucuronosyltransferases.

Specialized pro-resolving mediators (SPMs) are oxidized lipid mediators that have been shown to resolve inflammation in cellular and animal models as well as humans. SPMs and their biological precursors are even commercially available as dietary supplements. It has been understood for more than forty years that pro-inflammatory oxidized lipid mediators, including prostaglandins and leukotrienes, are rapidly inactivated via metabolism. Studies on the metabolism of SPMs are, however, limited. Herein, we report that resolvin D5 (RvD5) and resolvin D1 (RvD1), well-studied SPMs, are readily metabolized by human liver microsomes (HLM) to glucuronide conjugated metabolites. We further show that this transformation is catalyzed by specific uridine 5'-diphospho-glucuronosyltransferase (UGT) isoforms. Additionally, we demonstrate that RvD5 and RvD1 metabolism by HLM is influenced by non-steroidal anti-inflammatory drugs (NSAIDs), which can act as UGT inhibitors through cyclooxygenase-independent mechanisms. The results from these studies highlight the importance of considering metabolism, as well as factors that influence metabolic enzymes, when seeking to quantify SPMs in vivo.

OculoMotor & Vestibular Endurance Screening (MoVES) Normative, Repeatability, and Reliability Data.

This study aims to assess oculomotor and vestibular endurance by utilizing the Oculomotor and Vestibular Endurance Screening (MoVES) assessment in athletes' pre-season and post-season and after a suspected head injury to detect impairment. Athletes (N = 311, 19.4 ± 1.3 years) were recruited to perform the following seven tasks: (1) horizontal saccades, (2) vertical saccades, (3) vergence jumps, (4) horizontal vestibular-oculomotor reflex (VOR), (5) vertical VOR, (6) amplitude of accommodation (AoA), and (7) near point of convergence (NPC). At pre-season, the observed number of eye movements in 60 s are horizontal saccades (74 ± 13 initial 30 s; 67 ± 11 latter 30 s), vertical saccades (70 ± 13; 66 ± 10), vergence jumps (48 ± 12; 45 ± 13), horizontal VOR (38 ± 11; 38 ± 11), and vertical VOR (8 ± 11; 38 ± 11). These results establish a normative database for eye movements within the MoVES assessment and show consistency in the number of movements from pre-season to post-season. The initial results show a trending decrease in the number of eye movements in the initial days post-head injury, which improves to pre-season measures 14-21 days post-injury. This foundation can be used by future studies to explore the extent of binocular and vestibular endurance dysfunctions caused by head injuries that subside within two weeks.

Identification of novel F2-isoprostane metabolites by specific UDP-glucuronosyltransferases.

UDP-glucuronosyltransferases (UGTs) catalyze the conjugation of glucuronic acid with endogenous and exogenous lipophilic small molecules to facilitate their inactivation and excretion from the body. This represents approximately 35 % of all phase II metabolic transformations. Fatty acids and their oxidized eicosanoid derivatives can be metabolized by UGTs. F2-isoprostanes (F2-IsoPs) are eicosanoids formed from the free radical oxidation of arachidonic acid. These molecules are potent vasoconstrictors and are widely used as biomarkers of endogenous oxidative damage. An increasing body of evidence demonstrates the efficacy of measuring the ß-oxidation metabolites of F2-IsoPs rather than the unmetabolized F2-IsoPs to quantify oxidative damage in certain settings. Yet, the metabolism of F2-IsoPs is incompletely understood. This study sought to identify and characterize novel phase II metabolites of 15-F2t-IsoP and 5-epi-5-F2t-IsoP, two abundantly produced F2-IsoPs, in human liver microsomes (HLM). Utilizing liquid chromatography-mass spectrometry, we demonstrated that glucuronide conjugates are the major metabolites of these F2-IsoPs in HLM. Further, we showed that these molecules are metabolized by specific UGT isoforms. 15-F2t-IsoP is metabolized by UGT1A3, 1A9, and 2B7, while 5-epi-5-F2t-IsoP is metabolized by UGT1A7, 1A9, and 2B7. We identified, for the first time, the formation of intact glucuronide F2-IsoPs in human urine and showed that F2-IsoP glucuronidation is reduced in people supplemented with eicosapentaenoic and docosahexaenoic acids for 12 weeks. These studies demonstrate that endogenous F2-IsoP levels can be modified by factors other than redox mechanisms.

A Chitosan-based Hydrogel with PLCL, ZnO NPs, and Oligoelements: A Promising Antibiotic Scaffold for Tissue Engineering / Hidrogel de Quitosano con PLCL, ZnO NPs y Oligoelementos: Un Andamio Antibacteriano Prometedor para Ingeniería de Tejidos

ABSTRACT Tissue engineering involves anchorage-dependent cells cultured on scaffolds, with growth factors added to facilitate cell proliferation. Its use in transplants implies the risk of bacterial infection. The current contribution describes the preparation and antibacterial evaluation of a chitosan-based hydrogel physically cross-linked with poly(l-lactic-coɛ-caprolactone) (PLCL) and enriched with zinc oxide nanoparticles (ZnO NPs) and trace elements (potassium and magnesium). The material was developed as a scaffold with built-in antibacterial properties. Chitosan and PLCL are biocompatible support materials applied in medicine for the repair and regeneration of damaged tissues, objectives promoted by ZnO NPs and the aforementioned trace elements. The ZnO NPs were elaborated by chemical coprecipitation. The materials were characterized by XRD, FT-IR, and SEM. Antibacterial testing was performed with strains of Escherichia coli and Staphylococcus aureus by the Kirby-Bauer method, in accordance with the NCCLS and CLSI guidelines. It was possible to obtain a homogeneous hydrogel with adequate morphology and distribution of elements. The hydrogel with 300 mM of Mg, K, and ZnO NP's showed antibacterial inhibition halos of 13 mm for S. aureus and 19 mm for E. coli. This innovative biomaterial with trace elements holds promise for tissue engineering by considering the challenge of bacterial infection.

RESUMEN La ingeniería de tejidos involucra el uso de células cultivadas en andamios con adiciones de factores de crecimiento para facilitar la proliferación celular. Su uso en trasplantes implica riesgo de infección bacteriana. La contribución actual describe la preparación y evaluación antibacteriana de un hidrogel a base de quitosano físicamente reticulado con poli (l-láctico-co-ɛ-caprolactona) (PLCL) enriquecido con nanopartículas de óxido de zinc (NP de ZnO) y oligoelementos (potasio y magnesio). El material se desarrolló como un andamio con propiedades antibacterianas. El quitosano y el PLCL son materiales de soporte biocompatibles aplicados en medicina para la reparación y regeneración de tejidos dañados, propiedades promovidas por las NP´s de ZnO y los oligoelementos antes mencionados. Las NP de ZnO se elaboraron mediante coprecipitación química. Los materiales se caracterizaron por DRX, FT-IR y SEM. Las pruebas antibacterianas se realizaron con cepas de Escherichia coli y Staphylococcus aureus por el método de KirbyBauer de acuerdo con las guías NCCLS y CLSI. Se pudo obtener un hidrogel homogéneo con adecuada morfología y distribución de elementos. El hidrogel con 300 mM de NP ZnO y oligoelementos mostró halos de inhibición antibacteriana de 13 mm para S. aureus y 19 mm para E. coli. Este biomaterial innovador con oligoelementos es prometedor para la ingeniería de tejidos al considerar el desafío de la infección bacteriana.