Farmacología

URI permanente para esta comunidadhttps://hdl.handle.net/11441/11024

Examinar

Mostrando 1 - 3 de 3

Association between HLA DNA variants and long-term response to anti-TNF drugs in a Spanish pediatric inflammatory bowel disease cohort
(MDPI, 2023-01-16) Salvador-Martín, Sara; Zapata Cobo, Paula; Velasco, Marta; Palomino, Laura M.; Clemente, Susana; Segarra, Oscar; Millán Jiménez, Antonio; Merino Bohórquez, Vicente; Rodríguez, Alejandro; López Fernández, Luis Andrés; Universidad de Sevilla. Departamento de Farmacología; Universidad de Sevilla. Departamento de Farmacología, Pediatría y Radiología; Instituto de Salud Carlos III, España; Instituto de Investigación Sanitaria Gregorio Marañón. España; Comunidad Autónoma de Madrid; European Union (UE)
The genetic polymorphisms rs2395185 and rs2097432 in HLA genes have been associated with the response to anti-TNF treatment in inflammatory bowel disease (IBD). The aim was to analyze the association between these variants and the long-term response to anti-TNF drugs in pediatric IBD. We performed an observational, multicenter, ambispective study in which we selected 340 IBD patients under 18 years of age diagnosed with IBD and treated with anti-TNF drugs from a network of Spanish hospitals. Genotypes and failure of anti-TNF drugs were analyzed using Kaplan-Meier curves and Cox logistic regression. The homozygous G allele of rs2395185 and the C allele of rs2097432 were associated with impaired long-term response to anti-TNF drugs in children with IBD after 3 and 9 years of follow-up. Being a carrier of both polymorphisms increased the risk of anti-TNF failure. The SNP rs2395185 but not rs2097432 was associated with response to infliximab in adults with CD treated with infliximab but not in children after 3 or 9 years of follow-up. Conclusions: SNPs rs2395185 and rs2097432 were associated with a long-term response to anti-TNFs in IBD in Spanish children. Differences between adults and children were observed in patients diagnosed with CD and treated with infliximab.
Functional Features of the Exopolysaccharide Extracts Produced by Lactiplantibacillus Strains Isolated from Table Olives
(Royal Society of Chemistry, 2024) Lopez García, Elio; Marín Gordillo, Ana; Sánchez Hidalgo, Marina; Ávila Román, Francisco Javier; Romero Gil, Verónica; Bermúdez Oria, Alejandra; Benítez Cabello, Antonio; Garrido Fernández, Antonio; Rodríguez Gómez, Francisco; Arroyo López, Francisco Noé; Universidad de Sevilla. Departamento de Farmacología; European Union (UE); Ministerio de Ciencia e Innovación (MICIN). España; Junta de Andalucía
This study evaluates the functional characteristics of the exopolysaccharide (EPS) extracts produced by various strains of Lactiplantibacillus pentosus (LPG1, 119, 13B4, and Lp13) and Lactiplantibacillus plantarum (Lp15) isolated from table olives. None of the EPS crude extracts showed cytotoxicity when administered to THP-1 human macrophage cells at dosages ranging from 6.25 to 50 mug mL-1. Many exhibited anti-inflammatory properties (reduction of pro-inflammatory cytokines TNF-alpha and IL-6 production) and antioxidant activity (reduction of ROS%) when macrophages were stimulated with Escherichia coli lipopolysaccharide. Notably, the EPS extract produced by the L. pentosus LPG1 strain had the best results corroborated by western blot immune analysis for differential expression of COX-2, Nrf-2, and HO-1 proteins, with the most significant antioxidant and anti-inflammatory response observed at a dosage of 50 mug mL-1. Chemical analysis revealed that the EPS extract produced by this strain contains a heteropolymer composed of mannose (35.45%), glucose (32.99%), arabinose (17.93%), xylose (7.48%), galactose (4.03%), rhamnose (1.34%), and fucose (0.77%). Finally, we conducted response surface methodology to model the EPS extract production by L. pentosus LPG1 considering pH (3.48-8.52), temperature (16.59-33.41 °C) and salt concentration (0.03-8.77% NaCl) as independent variables. The model identified linear effects of salt and pH and quadratic effects of salt as significant terms. The maximum EPS extract production (566 mg L-1) in a synthetic culture medium (MRS) was achieved at pH 7.5, salt 7.0%, and a temperature of 20 °C. These findings suggest the potential for novel applications for the EPS produced by L. pentosus LPG1 as nutraceutical candidates for use in human diets.
Pretreatment with Oleuropein Protects the Neonatal Brain from Hypoxia-ischemia by Inhibiting Apoptosis and Neuroinflammation
(Sage, 2024) Reyes Corral, Marta; Gil González, Laura; González Díaz, Ángela; Tovar Luzón, Javier; Ayuso, María Irene; Lao Pérez, Miguel; Montaner, Joan; Puerta Vázquez, Rocío de la; Fernández Torres, Rut; Ybot González, Patricia; Universidad de Sevilla. Departamento de Química Analítica; Universidad de Sevilla. Departamento de Farmacología; Junta de Andalucía; European Union (UE)
Hypoxic-ischemic (HI) encephalopathy is a cerebrovascular injury caused by oxygen deprivation to the brain and remains a major cause of neonatal mortality and morbidity worldwide. Therapeutic hypothermia is the current standard of care but it does not provide complete neuroprotection. Our aim was to investigate the neuroprotective effect of oleuropein (Ole) in a neonatal (seven-day-old) mouse model of HI. Ole, a secoiridoid found in olive leaves, has previously shown to reduce damage against cerebral and other ischemia/reperfusion injuries. Here, we administered Ole as a pretreatment prior to HI induction at 20 or 100 mg/kg. A week after HI, Ole significantly reduced the infarct area and the histological damage as well as white matter injury, by preserving myelination, microglial activation and the astroglial reactive response. Twenty-four hours after HI, Ole reduced the overexpression of caspase-3 and the proinflammatory cytokines IL-6 and TNF-α. Moreover, using UPLC-MS/MS we found that maternal supplementation with Ole during pregnancy and/or lactation led to the accumulation of its metabolite hydroxytyrosol in the brains of the offspring. Overall, our results indicate that pretreatment with Ole confers neuroprotection and can prevent HI-induced brain damage by modulating apoptosis and neuroinflammation.

Examinar

Examinando Farmacología por Agencia financiadora "European Union (UE)"