Artículos (Instituto de Biomedicina de Sevilla (IBIS))

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Tratamiento de la bacteriemia por Staphylococcus aureus: evidencias y retos
(Elsevier, 2020-12) López-Cortés, Luis E.; Gálvez Acebal, Juan; Rodríguez-Baño, Jesús; Universidad de Sevilla. Departamento de Medicina; Gobierno de España; Instituto de Salud Carlos III
La bacteriemia por Staphylococcus aureus continúa siendo un reto diario para los clínicos. A pesar de todos los esfuerzos realizados, su mortalidad y morbilidad asociadas no han descendido de forma significativa en los últimos 20 años. Existe evidencia de que la adherencia a los indicadores de calidad para su manejo clínico es importante para mejorar el pronóstico de los pacientes, aunque su cumplimiento sigue siendo menor de lo deseado en muchos hospitales; en este sentido, la asistencia por especialistas en enfermedades infecciosas ha demostrado contribuir a reducir la mortalidad de estos pacientes. En este artículo se revisan los estudios clínicos más relevantes realizados en los últimos años con objeto de evaluar la eficacia y la seguridad de los fármacos alternativos a los clásicos. Sin embargo, estos siguen siendo utilizados en un alto porcentaje de pacientes, ya que los prometedores resultados obtenidos por esos fármacos alternativos y determinadas combinaciones en estudios in vitro y modelos animales no se han traducido en una evidente superioridad en los estudios clínicos con la frecuencia que se hubiera esperado. Dicho esto, existen datos que sugieren que determinadas alternativas pueden ofrecer ventajas en situaciones concretas. En general, es necesario un manejo individualizado y experto de los pacientes para decidir la mejor terapia en base al foco, la gravedad y las complicaciones, las características de los pacientes y los datos microbiológicos.
The challenge to improving and standardizing training in infectious diseases in Europe
(Elsevier, 2025-06) Rodríguez-Baño, Jesús; Skov, Robert L.; Friedland, Jon S.; Río, Carlos del; Akova, Murat; Zinkernagel, Annelies S.; Universidad de Sevilla. Departamento de Medicina
The recent COVID-19 pandemic once again demonstrates that infectious diseases pose a significant threat to humanity. Moreover, we are increasingly encountering emerging pathogens causing outbreaks, the growing problem of antimicrobial resistance threatens modern medicine, and the number of individuals at risk of serious infections is rising due to an ageing population and the more widespread use of immunosuppressive drugs and invasive procedures. Given these realities, it is no surprise that the medical specialty of infectious diseases (ID) has become a crucial component of modern clinical medicine, working in close collaboration with clinical microbiology and public health.
Effectiveness and tolerability of intravenous fosfomycin in treating complicated urinary tract infections caused by Escherichia coli: a prospective cohort study from the FOSFOMIC project
(Elsevier, 2025-05) Moreno Mellado, Elisa; Aslan, Abdullah Tarik; Akova, Murat; León, Eva; Merchante Gutiérrez, Nicolás; Vinuesa, David; Merino Bohórquez, Vicente; Rodríguez-Baño, Jesús; Docobo Pérez, Fernando; Gutiérrez Gutiérrez, Belén; Universidad de Sevilla. departamento de Medicina; Universidad de Sevilla. departamento de Farmacología; Universidad de Sevilla. departamento de Microbiología; CIBERINFEC; European Union (UE); Gobierno de España; Instituto de Salud Carlos III
Objectives: The FOSFOMIC study assessed the clinical and microbiological effectiveness, and safety of intravenous fosfomycin in treating complicated urinary tract infections (cUTIs) caused by Escherichia coli, in comparison with other intravenous antimicrobials. Methods: A prospective, multinational matched cohorts study involving adults with community-acquired cUTIs and receiving targeted therapy with intravenous fosfomycin or other first-line drugs (beta-lactams or fluoroquinolones) was conducted from November 2019 to May 2023 in ten centres from Spain, Italy, and Türkiye. Matching criteria included type of infection acquisition, Charlson and Pitt scores. Endpoints were clinical and microbiological cure, mortality, recurrence, and adverse effects. Analyses used conditional logistic regression and desirability of outcome ranking (DOOR). Results: Overall, 155 matched pairs were included. Clinical and microbiological cure rates were 65.2% (101/155; 95% CI, 57.4–72.2) and 63.2% (98/155; 95% CI, 55.4–70.4) with fosfomycin and comparators, respectively (adjusted OR, 1.09; 95% CI, 0.68–1.73; p 0.73). Mortality rates were 1.9% (3/155; 95% CI, 0.7–5.5) and 5.8% (9/155; 95% CI, 3.1–10.7), respectively (p 0.11). Recurrence rates were 14.2% (22/155; 95% CI, 9.6–20.6) in the fosfomycin group vs. 10.3% (16/155; 95% CI, 6.1–16.1) (p 0.39). Severe adverse effects occurred in 1.9% (3/155; 95% CI, 0.7–5.5) of patients treated with fosfomycin vs. 0.6% (1/155; 95% CI, 0.0–3.3) in the control group (p 0.62). Non-severe adverse effects were more frequent with fosfomycin, affecting 23.3% (36/155; 95% CI, 17.0–30.7) compared with 7.7% (12/155; 95% CI, 4.1–13.1) in the control group (adjusted OR, 5.36; 95% CI, 2.04–14.1; p < 0.001). In DOOR analysis, fosfomycin demonstrated comparable effectiveness in treating pyelonephritis (probability of better DOOR, 54.0%; 95% CI, 48.5–59.6) and in comparison with ceftriaxone (50.3%; 95% CI, 44.7–55.8), without evidence of inferiority in bacteraemic urinary tract infections (DOOR, 47.3%; 95% CI, 41.7–52.8). Discussion: Fosfomycin is a viable option for treating cUTIs caused by E. coli, allowing for diversification in the treatment of these high-incidence infections.
Venlafaxine-PLGA Nanoparticles Provide a Fast Onset of Action in an Animal Model of Depression Via Nose-to-brain
(Elsevier, 2025) Cayero Otero, María Dolores; Pérez Caballero, Laura; Suárez Pereira, Irene; Hidalgo Figueroa, María; Delgado Sequera, Alejandra; Montesinos, Juan Manuel; Berrocoso, Esther; Martín Banderas, Lucía; Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica; Universidad de Sevilla; Junta de Andalucía
Background: Current treatment of depression is hindered by the delayed onset of the action of antidepressant drugs, often resulting in treatment failure. Therefore, new therapeutic solutions are imperative. Methodology: Venlafaxine-loaded poly(lactic-co-glycolic acid) nanoparticles were produced by a double emulsion-solvent evaporation method. Cellular safety assessment and internalization assays were carried out in vitro in human olfactory neuroepithelium cells. The antidepressant effect of intranasal (nose-to-brain) nanoparticle administration was assessed in animals submitted to an animal model of depression by behavioral tests, including open-field, sucrose preference test and tail suspension test. Results: The drug entrapment efficiency (55–65 %), particle size (190–210 nm), polydispersity index (<0.2), and zeta potential ( 20 mV) of Venlafaxine-loaded poly(lactic-co-glycolic acid) nanoparticles were determined to be adequate. Nanoparticles did not show cytotoxic effects. Cell viability was more than 90 % for all formulations and concentrations assayed. The results of the quantitative and qualitative cell uptake assays were consistent, showing an evident internalization of the nanoparticles into the cells. Furthermore, venlafaxine-loaded nanoparticles administered for just 7 days were able to reverse the phenotype induced by a depressive-like model, showing a significant antidepressant-like effect compared to those treated with free venlafaxine. Conclusions: These findings indicated that intranasal venlafaxine-loaded poly(lactic-coglycolic acid) nanoparticles could become a viable technique for improving venlafaxine brain uptake via nose-to-brain. It could also be a promising nanoplatform for enhancing the treatment of depression.
Shaping current European mitochondrial haplogroup frequency in response to infection: the case of SARS-CoV-2 severity
(Nature Briefing, 2025-01) Cabrera Alarcón, José Luis; Cruz, Raquel; Rosa-Moreno, Marina; Latorre-Pellicer, Ana; Diz de Almeida, Silvia; SCOURGE cohort group; Medrano Ortega, Francisco Javier; Rodríguez Hernández, María A.; Morilla Romero de la Osa, Rubén; Valido Morales, Agustín S.; Enríquez, José Antonio; Universidad de Sevilla. Departamento de Medicina; Universidad de Sevilla. Departamento de Biología Celular; Universidad de Sevilla. Departamento de Enfermería; Instituto de Biomedicina de Sevilla (IBIS)
The frequency of mitochondrial DNA haplogroups (mtDNA-HG) in humans is known to be shaped by migration and repopulation. Mounting evidence indicates that mtDNA-HG are not phenotypically neutral, and selection may contribute to its distribution. Haplogroup H, the most abundant in Europe, improved survival in sepsis. Here we developed a random forest trained model for mitochondrial haplogroup calling using data procured from GWAS arrays. Our results reveal that in the context of the SARS-CoV-2 pandemic, HV branch were found to represent protective factors against the development of critical SARS-CoV-2 in an analysis of 14,349 patients. These results highlight the role of mtDNA in the response to infectious diseases and support the proposal that its expansion and population proportion has been influenced by selection through successive pandemics.
Importance Assigned to Breastfeeding by Spanish Pregnant Women and Associated Factors: A Survey-Based Multivariate Linear Correlation Study
(MDPI, 2024) Arnedillo Sánchez, Mª del Socorro; Suffo Aboza, José Antonio; Carmona Rodríguez, Miguel Ángel; Morilla Romero de la Osa, Rubén; Arnedillo Sánchez, Inmculada; Universidad de Sevilla. Departamento de Enfermería; Instituto de Biomedicina de Sevilla (IBIS); Universidad de Sevilla. CTS1141: Investigación Clínica Aplicada a los Cuidados y Nuevos Paradigmas Asistenciales; Universidad de Sevilla. CTS969: Innovación en Cuidados y Determinantes Sociales en Salud
Breastfeeding education, across all disciplines, is often inconsistent and lacking in expertise and confidence. However, recommendations from health professionals, the sociocultural environment, and previous knowledge and experiences significantly influence women’s decision to breastfeed. This study aimed to identify factors that promote the assignment of greater importance to breastfeeding and associated practical benefits. This retrospective cross-sectional study included 276 participants who completed a self-administered questionnaire. Descriptive and bivariate analyses were performed, and multivariate linear models were applied to identify factors influencing the importance assigned to breastfeeding. Most participants were married or in a relationship, were native Spaniards, had secondary or higher education, and had an average age of 32.6 years. Seventy percent met the physical activity recommendations, and 91% felt comfortable with their body image during pregnancy. The importance assigned to breastfeeding was high across various aspects, except for postpartum weight loss and body image. Group prenatal care was only significantly associated with the importance assigned to the breastfeeding technique (how to breastfeed). The obesogenic environment and the importance assigned to nutritional aspects and physical activity also turned out to be predictors, although not for all models. In our region, the educational strategy of antenatal care groups could contain gaps regarding the mother’s health, which should be addressed in the future to improve results regarding the initiation and continuation of breastfeeding.
Trastornos psiquiátricos y tabaquismo. Análisis de mortalidad
(Neumosur. Asociación de Neumología y Cirugía Torácica del Sur, 2023) Ignacio Expósito, María del Mar; Almadana Pacheco, Virginia; Benito Bernáldez, Cristina; Montserrat García, S.; Vilches Arenas, Ángel; Valido Morales, Agustín S.; Universidad de Sevilla. Departamento de Medicina Preventiva y Salud Pública; Universidad de Sevilla. Departamento de Medicina; Instituto de Biomedicina de Sevilla (IBIS); Universidad de Sevilla. CTS312: Análisis de la Demanda Sanitaria
La prevalencia de consumo de tabaco entre aquellos que padecen algún tipo de patología psiquiátrica es significativamente superior a la de la población general. Como consecuencia está descrita en la bibliografía una tasa de mortalidad asociada al tabaco de casi el doble con respecto al resto de la población. Objetivo: identificar factores clínicos, psicológicos o sociales que puedan influir en la probabilidad de éxitus a corto plazo en pacientes que realizan el programa de deshabituación tabáquica.
Tabaquismo y mortalidad. Análisis de los posibles factores relacionados
(Neumosur. Asociación de Neumología y Cirugía Torácica del Sur, 2023) Ignacio Expósito, María del Mar; Hurtado Gañán, M. G.; Perera Louvier, Rafael; Montserrat García, S.; Vilches Arenas, Ángel; Valido Morales, Agustín S.; Universidad de Sevilla. Departamento de Medicina Preventiva y Salud Pública; Universidad de Sevilla. Departamento de Medicina; Instituto de Biomedicina de Sevilla (IBIS); Universidad de Sevilla. CTS312: Análisis de la Demanda Sanitaria
El consumo de tabaco continúa siendo a día de hoy el primer factor de riesgo de mortalidad prevenible relacionado con las principales causas de muerte en el mundo. A pesar de que la mayoría de los pacientes que acuden a la consulta especializada de tabaquismo no se consideran enfermos por este motivo. Objetivo principal: conocer las principales características clínicas y psicológicas de aquellos pacientes que acuden a un programa de deshabituación tabáquica en una unidad especializada. Objetivo secundario: analizar posibles diferencias entre aquellos que fallecen en un plazo de 10 años.
Resultados iniciales con Citisina en la unidad de tabaquismo
(Neumosur. Asociación de Neumología y Cirugía Torácica del Sur, 2023) Ignacio Expósito, María del Mar; Hurtado Gañán, M. G.; Montserrat García, S.; Vilches Arenas, Ángel; Valido Morales, Agustín S.; Universidad de Sevilla. Departamento de Medicina Preventiva y Salud Pública; Universidad de Sevilla. Departamento de Medicina; Instituto de Biomedicina de Sevilla (IBIS); Universidad de Sevilla. CTS312: Análisis de la Demanda Sanitaria
Desde finales del año 2021 los pacientes con tabaquismo activo tienen una nueva opción terapéutica (no financiada) aprobada por la Agencia Española del Medicamento, Citisina (Todacitán ®). Objetivo: describir el perfil de pacientes y los resultados obtenidos tras la realización del programa para cesación tabáquica de los pacientes tratados con Citisina desde su aprobación en España en noviembre de 2021.
Diagnóstico precoz de EPOC y elaboración de un modelo predictivo en la consulta de deshabituación tabáquica
(Neumosur. Asociación de Neumología y Cirugía Torácica del Sur, 2023) Hurtado Gañán, M. G.; Ignacio Expósito, María del Mar; Vilches Arenas, Ángel; Valido Morales, Agustín S.; Universidad de Sevilla. Departamento de Medicina Preventiva y Salud Pública; Universidad de Sevilla. Departamento de Medicina; Instituto de Biomedicina de Sevilla (IBIS); Universidad de Sevilla. CTS312: Análisis de la Demanda Sanitaria
La enfermedad pulmonar obstructiva crónica (EPOC) tiene un elevado infradiagnóstico, que supone un retraso del mismo. Un entorno adecuado para su detección precoz podrían ser las Unidades de Tabaquismo, ya que el tabaco se trata de la causa fundamental de la EPOC en nuestro medio. El objetivo fue evaluar la incidencia de nuevos diagnósticos de EPOC en la unidad especializada de Tabaquismo del HUVM, además de elaborar un modelo predictivo de las características de estos pacientes.
Diabetes y tabaquismo. Análisis de mortalidad
(Neumosur. Asociación de Neumología y Cirugía Torácica del Sur, 2023) Ignacio Expósito, María del Mar; Pavón Masa, María; Hurtado Gañán, M. G.; Montserrat García, S.; Vilches Arenas, Ángel; Valido Morales, Agustín S.; Universidad de Sevilla. Departamento de Medicina Preventiva y Salud Pública; Universidad de Sevilla. Departamento de Medicina; Instituto de Biomedicina de Sevilla (IBIS); Universidad de Sevilla. CTS312: Análisis de la Demanda Sanitaria
Fumar es un factor de riesgo independiente para el desarrollo de Diabetes Mellitus 2 (DM2) y Síndrome Metabólico. Se ha demostrado que condiciona un peor control glucémico y aumenta el riesgo de complicaciones relacionadas con el daño macrovascular con tasas de mortalidad de hasta el doble con respecto a pacientes no DM2.
No association of a risk variant for severe COVID-19 with HIV protection in three cohorts of highly exposed individuals
(Oxford University Press, 2022-08-04) Sironi, Manuela; Cagliani, Rachele; Biasin, Mara; Lo Caputo, Sergio; Saulle, Irma; Forni, Diego; Real Navarrete, Luis Miguel; Pineda Vergara, Juan Antonio; Clerici, Mario; Universidad de Sevilla. Departamento de Medicina; Instituto de Biomedicina de Sevilla (IBIS); Ministerio de Economia, Industria y Competitividad (MINECO). España; European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER)
An extended haplotype on chromosome 3 is the major genetic risk factor for severe COVID-19. The risk haplotype, which was in herited from Neanderthals, decreases the expression of several cytokine receptors, including CCR5. Recently, a study based on three general population cohorts indicated that the minor allele of one of the variants in the haplotype (rs17713054) protects against HIV infection.We thus expectedthisallele to beover-represented in highly exposedindividuals whoremainuninfected(exposedseroneg ative individuals, ESN). To perform a meta-analysis, we genotyped rs17713054 in three ESN cohorts of European ancestry exposed to HIV through different routes. No evidence of association was detected in the single cohorts. The meta-analysis also failed to de tect any effect of the variant on protection from HIV-1. The same results were obtained in a Cox-regression analysis for the time to seroconversion. An in-vitro infection assay did not detect differences in viral replication as a function of rs17713054 genotype sta tus. We conclude that the rs17713054 minor allele is not associated with the ESN phenotype and does not modulate HIV infection in vitro.
Genetic associations between modifiable risk factors and Alzheimer disease
(Amer medical assoc, 2023-05-01) European Alzheimer’s & Dementia Biobank Mendelian Randomization (EADB-MR) Collaboration; Mir Rivera, Pablo; Real Navarrete, Luis Miguel; Universidad de Sevilla. Departamento de Medicina; Universidad de Sevilla. Departamento de Bioquímica Médica y Biología Molecular e Inmunología; Instituto de Biomedicina de Sevilla (IBIS)
IMPORTANCE An estimated 40% of dementia is potentially preventable by modifying 12 risk factors throughout the life course. However, robust evidence for most of these risk factors is lacking. Effective interventions should target risk factors in the causal pathway to dementia. OBJECTIVE To comprehensively disentangle potentially causal aspects of modifiable risk factors for Alzheimer disease (AD) to inspire new drug targeting and improved prevention. DESIGN, SETTING, AND PARTICIPANTS This genetic association study was conducted using 2-sample univariable and multivariable mendelian randomization. Independent genetic variants associated with modifiable risk factors were selected as instrumental variables from genomic consortia. Outcome data for AD were obtained from the European Alzheimer & Dementia Biobank (EADB), generated on August 31, 2021. Main analyses were conducted using the EADB clinically diagnosed end point data. All analyses were performed between April 12 and October 27, 2022. EXPOSURES Genetically determined modifiable risk factors. MAIN OUTCOMES AND MEASURES Odds ratios (ORs) and 95% CIs for AD were calculated per 1-unit change of genetically determined risk factors. RESULTS The EADB-diagnosed cohort included 39106 participants with clinically diagnosed AD and 401577 control participants without AD. The mean age ranged from 72 to 83 years for participants with AD and 51 to 80 years for control participants. Among participants with AD, 54% to 75% were female, and among control participants, 48% to 60% were female. Genetically determined high-density lipoprotein (HDL) cholesterol concentrations were associated with increased odds of AD (OR per 1-SD increase, 1.10 [95% CI, 1.05-1.16]). Genetically determined high systolic blood pressure was associated with increased risk of AD after adjusting for diastolic blood pressure (OR per 10-mm Hg increase, 1.22 [95% CI, 1.02-1.46]). In a second analysis to minimize bias due to sample overlap, the entire UK Biobank was excluded from the EADB consortium; odds for AD were similar for HDL cholesterol (OR per 1-SD unit increase, 1.08 [95% CI, 1.02-1.15]) and systolic blood pressure after adjusting for diastolic blood pressure (OR per 10-mm Hg increase, 1.23 [95% CI, 1.01-1.50]). CONCLUSIONS AND RELEVANCE This genetic association study found novel genetic associations between high HDL cholesterol concentrations and high systolic blood pressure with higher risk of AD. These findings may inspire new drug targeting and improved prevention implementation.
Immunological and senescence biomarker profiles in patients after spontaneous clearance of hepatitis C virus: gender implications for long-term health risk
(BMC (BioMed Central), 2023-11-17) Martín-Escolano, Rubén; Vidal-Alcántara, Erick Joan; Crespo, Javier; Ryan, Pablo; Real Navarrete, Luis Miguel; Lazo-Álvarez, Juan Ignacio; Fernández-Rodríguez, Amanda; Universidad de Sevilla. Departamento de Bioquímica Médica y Biología Molecular e Inmunología; Instituto de Biomedicina de Sevilla (IBIS)
Background About 25% of patients with acute hepatitis C virus (HCV) infection show spontaneous clearance within the first six months of infection but may remain at risk of inflammaging, aging, and liver and non liver disease complications. This study evaluated the differences in the plasma levels of immune checkpoints (ICs) and senescence associated secretory phenotype (SASP) biomarkers between patients who had spontaneously eliminated HCV infec tion (SC group) and individuals without evidence of HCV infection (C group). Methods We performed a multicenter retrospective study of 56 individuals: 32 in the SC and 24 in the C groups. ICs and SASP proteins were analyzed using a Luminex 200TM analyzer. The statistical analysis used Generalized Linear Models with gamma distribution (log link) adjusted by significant variables and sex. Results 13 ICs (BTLA, CD137(4 1BB), CD27, CD28, CD80, GITR, HVEM, IDO, LAG 3, PD 1, PD L1, PD L2, and TIM 3) and 13 SASP proteins (EGF, Eotaxin, IL 1alpha, IL 1RA, IL 8, IL 13, IL 18, IP 10, SDF 1alpha, HGF, beta NGF, PLGF 1, and SCF) were significantly higher in SC group after approximately more than two years of HCV clearance. After strati fying by sex, differences remained significant for males, which showed higher levels for 13 ICs and 4 SASP proteins in SC. While only PD L2 was significantly higher in SC women, and no differences in SASP were found. Conclusions Higher plasma levels of different IC and SASP proteins were found in individuals after more than two years of HCV clearance, mainly in men. Alterations in these molecules might be associated with an increased risk of developing liver and non hepatic diseases.
Comparative Effectiveness of Iontophoresis vs. Low Dye Taping in Plantar Fasciitis: A Systematic Review
(Springer Science and Business Media LLC, 2025-07-03) Castro Méndez, Aurora; Roldán-Fernández, Lucía; Tovaruela Carrión, Natalia; Pabón Carrasco, Manuel; Álvarez-Cordero, Juan; Vázquez‐Castro, M. A.; Universidad de Sevilla. Departamento de Podología; Universidad de Sevilla. Departamento de Enfermería; Universidad de Sevilla. CTS601: Hermes; Universidad de Sevilla. CTS1050: Cuidados Complejos, Cronicidad y Resultados en Salud
Background Plantar fasciitis (PF) is a frequent cause of heel pain, affecting approximately 10% of the population. Conserva tive treatments such as iontophoresis and low-dye taping (LDT) are widely used to alleviate symptoms, often providing short-term pain relief. Objective This systematic review aims to compare the efficacy of iontophoresis (with 5% acetic acid, 0.4% dexamethasone, dexamethasone and lidocaine, or placebo) versus low-dye taping (LDT) in treating plantar fasciitis. Additionally, it evaluates the combined effect of iontophoresis and LDT application. Methods A systematic search was conducted in Scopus, PubMed, Web of Science, CINAHL, and the Cochrane Library databases, following PRISMA guidelines and the Cochrane Handbook for Systematic Reviews of Interventions. Inclusion and exclusion criteria were predefined. Two independent reviewers screened and extracted data from eligible studies, assessing their quality. Included studies comprised randomized controlled trials, non-randomized clinical trials, case–control studies, systematic reviews, and meta-analyses. The review protocol was registered with PROSPERO (registration number: [blind for review]). Results Eight studies published between 1997 and 2018 were included, providing a moderate level of evidence. Both ion tophoresis (with the specified agents) and low-dye taping, alone or combined, were associated with statistically significant reductions in pain scores compared to baseline. Conclusion Iontophoresis and low-dye taping are effective conservative interventions for plantar fasciitis, with their com bined use also showing beneficial effects. These treatments can be considered viable options to reduce pain in patients with plantar fasciitis.
Enhanced Metabolic Syndrome Management Through Cannabidiol-Loaded PLGA Nanoparticles: Development and In Vitro Evaluation
(Wiley, 2025) El Hammadi, Mazen M.; Martín Navarro, Lucía; Berrocoso, Esther; Álvarez Fuentes, Josefa; Crespo Facorro, Benedicto; Suárez Pereira, Irene; Vázquez Bourgon, Javier; Martín Banderas, Lucía; Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica; Instituto de Investigación Valdecilla (IDIVAL); Ministerio de Ciencia e Innovación (MICIN). España; Gobierno de España
Cannabidiol (CBD) holds promise for managing metabolic diseases, yet enhancing its oral bioavailability and efficacy remainschallenging. To address this, we developed polymeric nanoparticles (NPs), using poly(lactic-co-glycolic acid) (PLGA), encapsu-lating CBD using nanoprecipitation, aiming to create an effective CBD-nanoformulation for metabolic disorder treatment. TheseNPs (135–265 nm) demonstrated high encapsulation efficiency (EE% ≈ 100%) and sustained release kinetics. Their therapeuticpotential was evaluated in an in vitro metabolic syndrome model employing sodium palmitate-induced HepG2 cells. Key as-sessment parameters included cell viability (MTT assay), glucose uptake, lipid accumulation (Oil Red O staining), triglycerides,cholesterol, HDL-c levels, and gene expression of metabolic regulators. Results showed an IC50 of 9.85 μg/mL for free CBD
Effects of Combined CBGA and Cannabis-derived terpene nanoformulations on TRPV1 Activation: Implications for Enhanced Pain Management
(Elsevier, 2025) El Hammadi, Mazen M.; Small Howard, Andrea L.; Fernández Arévalo, María Mercedes; Turner, Helen; Martín Banderas, Lucía; Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica; Universidad de Sevilla; National Institutes of Health (NIH)
Cannabinoids and terpenes, key bioactive components of cannabis, are increasingly studied for their individual and combined contributions to the therapeutic potential of cannabis-based treatments, with ongoing research exploring their distinct and interactive effects. This study aimed to encapsulate cannabigerolic acid (CBGA) in poly(ethylene glycol)-poly(lactic-co-glycolic acid) nanoparticles (PEG-PLGA NPs) and investigate the effects of combining CBGA NPs with cannabis-derived terpene-loaded NPs (myrcene [MC], nerolidol [NL], and caryophyllene [CPh]) for potential applications in pain management. CBGA NPs (152 nm) and terpene-loaded NPs (233–297 nm) were prepared via nanoprecipitation and emulsion-solvent evaporation, respectively, exhibiting a polydispersity index < 0.3 and negative zeta potentials (−23 to −26 mV). Encapsulation efficiency was 98.6 % for CBGA and 13–33 % for terpenes. CBGA release followed a biphasic profile, with ∼ 20 % released within 4 h and sustained release over 72 h. In vitro evaluation used HEK293 cells expressing the nociceptive transient receptor potential vanilloid-1 (TRPV1) channel, a key mediator of pain perception. TRPV1 activation was assessed via calcium influx kinetics (Fluo-4 indicator). The EC50 values were 23.8 µg/mL (CBGA NPs), 8.0 µg/mL (MC NPs), 6.7 µg/mL (NL NPs), and 13.3 µg/mL (CPh NPs). Combinatorial treatments of CBGA NPs with terpene NPs at their respective EC50 concentrations revealed significantly enhanced calcium influx compared to individual NPs, with the strongest interaction observed for CBGA/NL and moderate effects for CBGA/MC. Fluorescence imaging further corroborated these findings. These results suggest that combining CBGA NPs with terpene-loaded NPs could potentiate pain-relief efficacy, offering a promising strategy for advanced therapeutic formulations.
Homocysteine and C-reactive protein levels are associated with frailty in older spaniards: the Toledo study for healthy aging
(Oxford University Press, 2019-07-13) Álvarez-Sánchez, Nuria; Álvarez-Ríos, Ana Isabel; Guerrero Montávez, Juan Miguel; García-García, Francisco J.; Rodríguez-Mañas, Leocadio; Cruz Chamorro, Iván; Lardone, Patricia Judith; Carrillo Vico, Antonio; Universidad de Sevilla. Departamento de Bioquímica Médica y Biología Molecular e Inmunología; Instituto de Biomedicina de Sevilla (IBIS); Consejería de Salud, Junta de Andalucía; Instituto de Salud Carlos III (Ministerio de Ciencia e Innovación); Instituto de Salud Carlos III (Red Temática de Investigación Cooperativa en Envejecimiento y Fragilidad); Junta de Andalucía; Ministerio de Educación, Cultura y Deporte (MECD). España; Universidad de Sevilla. CTS160: Neuroinmunoendocrinología Molecular
High-sensitivity C-reactive protein (hsCRP) and homocysteine (Hcy) are inflammation markers but are also related to cardiovascular diseases, disability, or higher risk of death. Although inflammation is considered to be associated with frailty, data regarding the association between hsCRP or Hcy and frailty are controversial or scarce, especially with respect to their association with prefrailty. Thus, our objective was to study the association of hsCRP and Hcy with prefrailty and frailty in 1,211 Spanish men and women aged 65–98 years from the Toledo Study for Healthy Aging (TSHA) cohort, classified according to Fried’s criteria. Hcy was independently associated with frailty (odds ratio [OR] = 1.06; 95% confidence interval [CI]: 1.01–1.12), whereas hsCRP was independently associated with both prefrailty (OR = 1.03; 95% CI: 1.01–1.06) and frailty (OR = 1.07; 95% CI: 1.02–1.12). Furthermore, both markers were positively correlated with the number of Fried’s criteria that were met and were independently associated with the criteria of exhaustion (Hcy: OR = 1.03, 95% CI: 1.00–1.06), weakness (hsCRP: OR = 1.03, 95% CI: 1.01–1.05), and low physical activity (hsCRP: OR = 1.04, 95% CI: 1.02–1.06). Thus, our results highlight the importance of inflammation in age-related physical decline and, in particular, its association with fatigue, low strength, and decreased physical activity.
Seasonal variations in macrophages/microglia underlie changes in the mouse model of multiple sclerosis severity
(Humana press INC; Springer, 2020-07-13) Alvarez Sanchez, Nuria; Cruz Chamorro, Iván; Álvarez-López, Ana I.; López-González, Antonio; Lacalle Remigio, Juan Ramón; Lardone, Patricia Judith; Guerrero Montávez, Juan Miguel; Martinez Lopez, Alicia; Carrillo Vico, Antonio; Universidad de Sevilla. Departamento de Medicina Preventiva y Salud Pública; Universidad de Sevilla. Departamento de Bioquímica Médica y Biología Molecular e Inmunología; Instituto de Biomedicina de Sevilla (IBIS); Consejería de Salud de la Junta de Andalucía; Beca FPU del Ministerio de Educación, Cultura y Deporte de España; Red Nacional RETICEF de Estudios sobre Envejecimiento (Red Temática de Investigación Cooperativa en Envejecimiento y Fragilidad del Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación de España); Programa PAIDI de la Junta de Andalucía; Universidad de Sevilla. CTS312: Análisis de la Demanda Sanitaria; Universidad de Sevilla. CTS160: Neuroinmunoendocrinología Molecular
Both immune and neurodegenerative mechanisms underlie multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). MS/EAE are triggered by encephalitogenic immune cells, including Th1 and Th17 cells, whereas T regulatory (Treg) cells are involved in inflammation resolution. Pro-inflammatory macrophages/microglia also play a deleterious role in the disease. Seasonal variations in MS relapses, active lesions, and pro- and anti-inflammatory cytokine levels have been described in MS patients and have been related with both perinatal and adult exposure to sunlight and other environmental factors. However, some data in EAE mice suggest that these variations might be, at least partially, endogenously determined. Thus, our objective was to study the effect of the season of birth and disease induction on the course of EAE, and immune cell infiltration in the central nervous system (CNS) in myelin oligodendrocyte glycoprotein (MOG35-55)-induced EAE in 8 weeks old, female C57BL/6N mice maintained under constant, controlled conditions. EAE severity as well as pathogenic (Th1, Th17, macrophages/microglia) and protective (Treg) subsets was found to vary according to the season of birth or of EAE induction. Summer-born or summer-immunized animals developed a milder disease, which coincided with variations in numbers of T effector/regulatory subsets, and significantly low numbers of macrophages/microglia. These results suggest that endogenous rhythms in immune responses might cause seasonal variations in EAE severity, and, maybe, in the course of MS, and that they might be related to macrophages/microglia.
Encuesta a profesionales sobre la Asistencia en Salud Mental Perinatal en Hispanoamérica: Análisis de resultados
(Instituto Psiquiatría Psicodex, 2025) Marti Oristrell, Nuria; Cobo, Jesús; Lasheras, Gracia; Crespo, Elena; Martínez, Verónica; Parramon-Puig, Gemma; Sanz, Cristina; Andreu, Laura; Motrico Martínez, Emma; Hernández, Carmen; Trautmann-Villalba, Patricia; Palacios-Hernández, Bruma; Osma, Jorge; Universidad de Sevilla. Departamento de Psicología Evolutiva y de la Educación
Introducción: Los problemas de salud mental perinatal (SMP) son aquellos que ocurren desde la concepción hasta el primer año del bebé. En América Latina, la depresión posparto (DPP) puede alcanzar el 20.5%, y hasta el 15% en el estado español, constituyendo un gran desafío de salud pública. Sin embargo, la detección y el tratamiento son insuficientes en todos los países hispanohablantes o ciertas áreas, especialmente en aquellos de menos ingresos. Objetivo: Identificar recursos asistenciales y formativos para la atención de la SMP en países hispanohablantes y detectar brechas y oportunidades. Metodología: Se realizó una encuesta en línea semiestructurada a profesionales de SMP entre diciembre de 2022 y enero de 2023, analizando los datos con SPSS. Resultados: Se obtuvieron 48 respuestas de 13 países, destacando Argentina y España por número de respuestas. Más del 60% reportó falta de asistencia pública en SMP, salvo en Argentina, España y Chile. El 70% reportó servicios disponibles en el sector privado. En cuanto a la detección, el 71% desconocía procedimientos específicos en el ámbito público, mientras que, en el privado, el 55% en España y el 75% en Chile utilizan herramientas para DPP. Solo el 25% conocía guías oficiales y el 41.47% reportó información sobre formación en SMP, con ciertos datos contradictorios o desconocimiento sobre opciones formativas. Conclusiones: Este análisis preliminar de los datos enfatiza la necesidad de mejorar los conocimientos disponibles sobre los servicios y la asistencia a la SMP en todos los países hispanohablantes. Es necesario contar con datos reales para poder mejorar la planificación y las estrategias futuras, desarrollando y reforzando las estructuras actuales y aprovechando todas las fortalezas disponibles, en especial las formativas.

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