Artículos (Farmacología)

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Implementation and Evaluation of a Real-Time Prescription Alert System to Optimize Antiretroviral Therapy and Medication Adherence in People Living with HIV. SANPAT PROJECT
(Dovepress, 2025-11-07) Morillo Verdugo, Ramón Alejandro; Contreras-Macías, Enrique; Márquez-Saavedra, Esther; Robustillo-Cortés, María de las Aguas; Romero Gil, Eloy; Contreras-Macías, Enrique; Farmacología
Purpose: To evaluate the clinical and implementation impact of “Alert System for New Prescriptions and Therapeutic Adherence Monitoring” (SANPAT), a real-time prescription alert system embedded in a structured pharmaceutical care model, aimed at optimizing antiretroviral therapy (ART) and improving medication adherence in people living with HIV (PLWH). Patients and Methods: A quasi-experimental, before-and-after study was conducted in a hospital outpatient pharmaceutical care unit in Andalusia, Spain. Patients aged ≥ 50 years receiving ART were included if they had polypharmacy (≥ 6 concurrent medications) or demonstrated poor adherence. The pre-intervention period (Feb 2023–Jan 2024) relied on standard care without alerts. The post-intervention period (Feb 2024–Jan 2025) incorporated SANPAT, enabling pharmacists to receive real-time alerts for new prescriptions and adherence risks. Pharmaceutical interventions were classified using a validated Capacity-Motivation-Opportunity (CMO)-based taxonomy, and implementation was evaluated using the Reach, Effectiveness, Adoption, Implementation y Maintenance (RE-AIM) framework. Results: A total of 153 patients were included (84 pre- and 69 post-intervention). The number of pharmacist interventions increased markedly post-intervention (from 84 to 877 events), especially in adherence support (0.0% to 47.2%) (p< 0.001) and medication error prevention (0.0% to 34.7%) (p< 0.001). The frequency of polypharmacy and major polypharmacy increased, while immunovirological risk markers improved (CD4 cell count< 200 cells/μL decreased from 15.0% to 4.3%; detectable viral load from 20.3% to 3.6%) (p< 0.001). The RE-AIM evaluation demonstrated broad reach, high adoption, improved implementation metrics, and early signs of long-term sustainability. Conclusion: SANPAT significantly enhanced the timely identification and resolution of pharmacotherapeutic risks in PLWH, supporting personalized interventions and optimizing ART management. Its integration within existing electronic prescribing populations.platforms and structured care models represents a scalable strategy to improve medication safety in aging and complex patients.
Knowledge, perception, and willingness to implement the CMO (Capability- Motivation-Opportunity) methodology among specialist physicians caring for patients with HIV in Spain
(Sociedad Española de Farmacia Hospitalaria (SEFH), 2025-09-18) Contreras Macías, Enrique; Taberner Bonastre, Pilar; Corma Gómez, Anaïs; Blanco Ramos, José Ramón; Morillo Verdugo, Ramón Alejandro; Farmacología
Introduction: The CMO (Capability-Motivation-Opportunity) methodology is an innovative pharmaceutical care model designed to improve the quality of care for people living with HIV (PLWH). This approach evaluates the knowledge, perception, and willingness to implement the methodology among specialist physicians in Spain. Methods: This observational and descriptive study utilized a validated questionnaire distributed among clinicians involved in the care of PLWH. The survey assessed their knowledge and perception of the methodology. Associations between variables were analyzed using bivariate tests. Results: Thirty physicians participated. Sixty percent reported moderate-to-high knowledge of the methodology, correlating with a positive perception of its clinical relevance (p = 0.02). Motivational interviewing and remote follow-up were identified as key tools. Conclusion: Knowledge of the CMO methodology is limited but positively valued. Its association with improved quality of health care underscores the importance of strategies to enhance its dissemination and adoption in clinical practice
Oleocanthal Supplemented Diet Improves Renal Damage And Endothelial Dysfunction In Pristane-Induced Systemic Lupus Erythematosus In Mice
(Elsevier, 2023) Montoya García, Tatiana; Sánchez Hidalgo, Marina; Castejón Martínez, María Luisa; Vázquez Román, María Victoria; Álvarez de Sotomayor Paz, María; Ortega Vidal, Juan; González Rodríguez, María Luisa; Alarcón de la Lastra Romero, Catalina; Farmacología; Citología e Histología Normal y Patológica; Farmacia y Tecnología Farmacéutica; Ministerio de Economía y Competitividad (MINECO). España; Junta de Andalucía
Systemic lupus erythematosus (SLE) is a multiorgan disorder with a deregulated immune-inflammatory response. Nutritional therapy has been considered a promising approach to SLE management. Oleocanthal (OLE), the main extra virgin olive oil (EVOO)-derived secoiridoid, has shown to regulate the immune-inflammatory response in various disease contexts; however, its possible beneficial effects on SLE remain unclear. This study sought to evaluate the effects of OLE enriched diet on renal damage and aortic endothelial dysfunction in murine pristane-induced SLE, focusing on the action mechanisms and signaling pathways involved. BALB/c mice were injected with pristane and fed with OLE supplemented diet (0.01 % (w/w)) for six months. Levels of cytokines were measured by ELISA in lipopolysaccharide (LPS)-stimulated peritoneal macrophages and splenocytes. Presence of IgG and IgM immune complexes was examined by immunofluorescence and immunohistochemistry. Thoracic aortas were used to evaluate endothelial dysfunction. Western blotting was employed to detect signaling pathways and oxidative-inflammatory-related mediators. Dietary OLE supplementation reduced Th1/Th17 pro-inflammatory cytokines production and alleviated renal damage by decreasing immunoglobulin complexes deposition, and inflammation-mediating enzymes expression. The mechanisms underlying these protective effects could be related to the regulation of nuclear factor erythroid 2-related factor 2/Haem oxygenase 1 (Nrf-2/HO-1), mitogen-activated protein kinases (MAPKs), signal transducer and transcription activator of transcription (STAT-3), inflammasome and, nuclear factor kappa B (NF-B) signaling pathways. Also, dietary OLE improved aortic endothelial dysfunction and vascular reactivity, normalizing endothelial nitric oxide synthase (eNOS) uncoupling, and NADPH oxidase-1 (NOX-1) overexpression. This study shows the immunomodulatory effects of OLE in an in vivo model of SLE by improving renal damage and regulating aortic endothelial dysfunction. These preliminary results provide OLE as a new therapeutic strategy in SLE management.
Pharmacokinetic/pharmacodynamic optimization of temocillin treatment against CTX-M-15-producing Klebsiella pneumoniae isolates in a hollow-fiber infection model
(American Society Microbiology, 2025-11-12) Rodríguez Ochoa, José Luis; Saúco Carballo, Carlos; Pérez Palacios, Patricia; Merino Bohórquez, Vicente; Velázquez Escudero, Ana; López Cerero, Lorena; Rodríguez-Baño, Jesús; Rodríguez Martínez, José Manuel; Pascual Hernández, Álvaro; Docobo Pérez, Fernando; Farmacología; Microbiología; Medicina; Instituto de Salud Carlos III; Junta de Andalucía
Temocillin, a β-lactam antibiotic, has been proposed as an alternative to carbapenems for the treatment of ESBL-producing Enterobacteriaceae. The present EUCAST breakpoints for temocillin are established based on exposure levels derived from a dosing regimen of 2 g every 8 h via intermittent infusion (II). However, the evidence supporting the efficacy of continuous infusion (CI) against ESBL-producing Klebsiella pneumoniae remains limited. The objective of the present study was to evaluate whether CI improves temocillin activity compared with II in a hollow-fiber infection model (HFIM) against CTX-M-15-producing K. pneumoniae. Four clinical isolates were characterized by whole-genome sequencing and tested for temocillin susceptibility. Mutant frequen cies were estimated, and temocillin activity was assessed via time–kill assays and HFIM simulating human pharmacokinetics of temocillin 6 g/day via II and CI. Bacterial counts were performed to detect total and resistant subpopulations. Isolates showing regrowth were sequenced to identify resistance associated mutations. The results showed that both regimens reduced bacterial burden within 8 h. However, three isolates regrew under II, while only one did under CI. CI achieved more sustained bacterial suppression and delayed or prevented the emergence of resistant subpopulations. Mutations in the cpxA gene were associated with increased temocillin MICs in regrown isolates. While both regimens demonstrated initial bactericidal activity, CI was more effective in sustaining bacterial suppression and limiting resistance emergence. These findings support the potential clinical benefit of CI for treating infections caused by CTX-M-15- producing K. pneumoniae and warrant further clinical validation.
The fruit of Corema album (L.) D. Don, a singular white berry with potential benefits in nutrition and health
(Springer Nature, 2021-11-15) León González, Antonio José; Navarro Zafra, Inmaculada; Acero, Nuria; Muñoz-Mingarro, Dolores; Martín Cordero, Carmen; Farmacología
Corema album (L.) D. Don (Ericaceae) is an endemic bush that grows along the Atlantic littoral of the Iberian Peninsula. Its edible white berries (known as camarinas, camariñas, camarinhas, white crowberry, among other vernacular names) have been used in popular medicine as an antipyretic and are consumed in localised areas of Portugal and Spain as appetisers and in the preparation of juices and jams. The aim of the present review is to summarise the knowledge of the chemical composition and pharmacological studies performed with C. album fruit and extracts. These berries are rich in phenolic compounds, including phenolic acids, stilbenes, flavonols, flavanones, prenylated flavanone, flavanols, and anthocyanins. The total phenolic content of various extracts of the pulp of these berries has been positively correlated with their antioxidant capacity. In this respect, the treatment with acetone, ethyl acetate, and aqueous extracts of this fruit has protected HepG2 cells against chemically induced oxidative stress. The chemoprotective effect of these extracts is mediated by preventing reactive oxygen species formation, reduced glutathione depletion, antioxidant enzyme over-activity, and oxidative damage to proteins and lipids. Furthermore, the presence of pentacyclic triterpenes, such as ursolic and oleanolic acids, in C. album berries confers reflectance UV properties to this fruit and derived extracts. In short, existing studies suggest that the development of C. album crops should be considered as a promising opportunity to obtain these remarkable berries. Moreover, further experiments should also be designed to evaluate their in vivo effect and to ascertain the underlying mechanism of action.
d-Pinitol: a cyclitol with versatile biological and pharmacological activities
(Springer Nature, 2020-05-13) Sánchez Hidalgo, Marina; León González, Antonio José; Gálvez-Peralta, Marina; González-Mauraza, Nuria H.; Martín Cordero, Carmen; Farmacología; Instituto de Salud Carlos III
d-Pinitol (3-O-methyl-d-chiro-inositol) is a cyclitol nearly ubiquitous in the Leguminosae and Pinaceae families. It plays an important role in plants as physiological cellular modulator and chemical defense against unfavorable environmental conditions, such as water deficit and high level of salinity. Plants rich in d-pinitol are being used in traditional medicine as empirical treatment for diabetes, inflammation, cancer or infections. This review summarizes the extensive literature published about d-pinitol biosynthesis, plant distribution, biological activities and pharmacological studies, including in vitro, in vivo, and clinical trials.
Comparison of perceived versus actual care complexity in HIV-positive patients receiving antiretroviral treatment: The STRATPATIENT study
(index, 2025) García Galindo, Cristina; Contreras Macías, Enrique; Naranjo Pérez, Gema Araceli; Morillo Verdugo, Ramón Alejandro; Farmacología
Introduction: HIV is now considered a chronic disease due to advances in antiretroviral therapy (ART), which have improved survival but have also increased both comorbidities and polypharmacy. This underscores the need for personalized care strategies such as the Capacity-Motivation-Opportunity (CMO) model and patient stratification tools. This study aimed to identify the discrepancy between patient-perceived and actual care complexity in HIV-positive patients on ART, as assessed by a stratification tool. Methods: A retrospective, observational study at Valme Hospital (April-June 2024) included HIV-positive patients aged over 18 years on stable ART, excluding clinical trial participants. Data collected included age, sex, route of HIV acquisition, viral load, CD4 count, AIDS stage, comorbidities, polypharmacy and the Medication Regimen Complexity Index (MRCI). Perceived complexity was assessed using a visual analogue scale, whereas complexity according to the stratification tool was calculated with the variables of the CMO model. Results: A total of 411 participants with a median age of 55 years were included, of whom 72.5 % had comorbidities, primarily cardiovascular. The median MRCI score was 8, with 85.4 % of patients were classified at stratification level 3, while 74.9 % reported low perceived healthcare complexity. Concordance between stratification and perceived complexity was weak. Significant associations were observed between perceived complexity and AIDS stage, extensive polypharmacy, and stratification levels. Conclusions: This study emphasises integrating objective assessments and patient perspectives to improve healthcare evaluation and patient-centered care.
High rate of major drug–drug interactions of lopinavir–ritonavir for COVID-19 treatment
(Nature Publishing Group; Nature Portfolio, 2020-12-01) Macías Sánchez, Juan; Pinilla, Ana; Lao-Dominguez, Francisco A.; Corma, Anaïs; Contreras Macías, Enrique; González-Serna Martín, Manuel Alejandro; Morillo Verdugo, Ramón Alejandro; Real Navarrete, Luis Miguel; Pineda Vergara, Juan Antonio; Medicina; Fisiología; Farmacología; Bioquímica Médica y Biología Molecular e Inmunología
The impact of drug–drug interactions (DDI) between ritonavir-boosted lopinavir (LPV-r) to treat patients with coronavirus disease 2019 (COVID-19) and commonly used drugs in clinical practice is not well-known. Thus, we evaluated the rate and severity of DDI between LPV-r for COVID-19 treatment and concomitant medications. This was a cross-sectional study including all individuals diagnosed of SARS-CoV-2 infection treated with LPV-r and attended at a single center in Southern Spain (March 1st to April 30th, 2020). The frequency [95% confidence interval (95% CI)] of potential and major DDI were calculated. Overall, 469 patients were diagnosed of COVID-19, 125 (27%) of them were prescribed LPV-r. LPV-r had potential DDI with concomitant medications in 97 (78%, 95% CI 69–85%) patients, and in 33 (26%, 95% CI 19–35%) individuals showed major DDI. Twelve (36%) patients with major DDI and 14 (15%) individuals without major DDI died (p = 0.010). After adjustment, only the Charlson index was independently associated with death [adjusted OR (95% CI) for Charlson index ≥ 5: 85 (10–731), p < 0.001]. LPV-r was discontinued due to side effects in 31 (25%) patients. Management by the Infectious Diseases Unit was associated with a lower likelihood of major DDI [adjusted odds ratio (95% CI): 0.14 (0.04–0.53), p = 0.003). In conclusion, a high frequency of DDI between LPV-r for treating COVID-19 and concomitant medications was found, including major DDI. Patients with major DDI showed worse outcomes, but this association was explained by the older age and comorbidities. Patients managed by the Infectious Diseases Unit had lower risk of major DDI.
Cannabinoid effective targeting of atherosclerotic plaques by optimized-PLGA nanoparticles
(Elsevier, 2025-08-25) Martín Navarro, Lucía; Herrera González, María Dolores; Álvarez Fuentes, Josefa; Claro Cala, Carmen María; Martín Banderas, Lucía; Farmacia y Tecnología Farmacéutica; Farmacología; Junta de Andalucía; European Union (UE); Ministerio de Ciencia, Innovación y Universidades (MICIU). España; Agencia Estatal de Investigación. España
Aim While selective CB2 receptor agonists hold significant promise for mitigating inflammation and atherosclerosis, their poor physicochemical properties have hampered clinical translation. To overcome this, we engineered a sophisticated, nanoparticle-based delivery system designed for precise cannabinoid deposition at atheromatous plaque sites. Our approach utilized PEGylated PLGA nanoparticles (NPs), functionalized with a peptide ligand specifically targeting vascular cell adhesion molecule-1 (VCAM-1), a well-established biomarker of atherosclerotic lesions. Methods PEGylated PLGA NPs were synthesized via nanoprecipitation using a blend of PLGA, PLGA-PEG, and PLGA-PEG-Mal polymers. Peptide conjugation was then achieved through a maleimide-click reaction. The resulting functionalized nanoparticles were characterized for their physicochemical properties and evaluated both in vitro (using human vascular endothelial cells), and in vivo (in apolipoprotein E-deficient, ApoE-/-, mice). Results Optimal NP functionalization with the VBP peptide was achieved using a 1:1 maleimide-to-ligand molar ratio in 10 mM HEPES / 0.4 mM EDTA buffer after a 2-hour incubation. In vitro assays demonstrated that these functionalized NPs significantly downregulated the expression of adhesion molecules, inflammatory cytokines, and chemokines, while also successfully restoring oxidative balance in human endothelial cells. Importantly, in vivo experiments demonstrated efficient and site-specific delivery of the functionalized NPs to atheroprone regions in ApoE⁻/⁻ mice, resulting in a significant reduction of atherosclerotic plaque formation in the aortic sinus. Conclusion These findings indicate that this developed nanosystem represents a highly promising strategy for targeted cannabinoid delivery. This breakthrough could significantly contribute to the advancement of novel anti-atherogenic therapies, offering a new avenue for treating atherosclerosis.
Aplicación de la etnogeografía de plantas medicinales a la Ordenación de los Recursos Naturales tropicales: República Dominicana
(Asociación Española de Geografía, 2025-06-20) Quílez Guerrero, Ana María; Díaz del Olmo, Fernando; Cámara Artigas, Rafael; Geografía Física y Análisis Geográfico Regional; Farmacología; RNM915: Estudios Tropicales y Biogeografía; RNM273: Cuaternario y Geomorfología; CTS388: Plantas Medicinales
Se presenta una metodología de aplicación para el conocimiento de la distribución territorial del uso tradicional de plantas medicinales y su aplicación a la ordenación de los recursos naturales. La metodología de ordenación de recursos naturales se basa en la desarrollada por el grupo de investigación en asesorías técnicas internacionales en Iberoamérica y África, basada en la utilización de encuestas socioambientales para conocer el entramado social, sentimiento de pertenencia y uso y conocimiento de sus recursos naturales. Se aplica los niveles de ordenación en tres grandes categorías A, B, C, divida en 11 subcategorías, con normas de manejo y gestión. El objetivo es tener estos resultados en consideración para establecer las directrices de ordenación. En el caso de los recursos etnogeográficos se plantean encuestas sectoriales en las que se valora las partes usadas de las plantas medicinales y su estatus biológico para poder establecer regulaciones de uso. La metodología usada permite establecer directrices de gestión y manejo de este recurso en las zonas A y C de ordenación, y se plantean medidas de actuación vinculadas a la conservación de conocimiento del uso como recurso de la medicina tradicional como patrimonio cultural, especialmente en los países en vías de desarrollo.
Phytochemical Analysis and Therapeutic Potential of Tuberaria lignosa (Sweet) Samp. Aqueous Extract in Skin Injuries
(MDPI, 2025-07-25) González Vázquez, Manuel; Quílez Guerrero, Ana María; Zuzarte, Mónica; Salgueiro, Lígia; Alves Silva, Jorge; González Rodríguez, María Luisa; Puerta Vázquez, Rocío de la; Farmacología; Farmacia y Tecnología Farmacéutica; Caixa Catalunya
Tuberaria lignosa (Sweet) Samp. (Cistaceae) is a herbaceous species native to southwestern Europe, traditionally used to treat wounds, ulcers, and inflammatory or infectious skin conditions. This study aimed to characterize the phytochemical profile of its aqueous leaf extract and evaluate its skin-related in vitro biological activities. The phenolic composition was determined using UHPLC-HRMS/MS, HPLC-DAD, and quantitative colorimetric assays. Antioxidant activity was assessed against synthetic free radicals, reactive oxygen and nitrogen species, transition metals, and pro-oxidant enzymes. Enzymatic inhibition of tyrosinase, hyaluronidase, collagenase, and elastase were evaluated using in vitro assays. Cytocompatibility was tested on human keratinocytes and NIH/3T3 fibroblasts using MTT and resazurin assays, respectively, while wound healing was evaluated on NIH/3T3 fibroblasts using the scratch assay. Antifungal activity was investigated against several Candida and dermatophyte species, while antibiofilm activity was tested against Epidermophyton floccosum. The extract was found to be rich in phenolic compounds, accounting for nearly 45% of its dry weight. These included flavonoids, phenolic acids, and proanthocyanidins, with ellagitannins (punicalagin) being the predominant group. The extract demonstrated potent antioxidant, anti-tyrosinase, anti-collagenase, anti-elastase, and antidermatophytic activities, including fungistatic, fungicidal, and antibiofilm effects. These findings highlight the potential of T. lignosa as a valuable and underexplored source of bioactive phenolic compounds with strong potential for the development of innovative approaches for skin care and therapy.
Dietary freeze-dried beer prevents inflammation in DSS-induced chronic ulcerative colitis in mice
(Royal Society of Chemistry, 2025-07-01) Paredes Sánchez, María; Muñoz García, Rocío; Ávila Román, Francisco Javier; Lobo Prieto, Ana; Orta Cuevas, María del Mar; García González, Diego L.; Vázquez Román, María Victoria; Talero Barrientos, Elena Mª; Sánchez Hidalgo, Marina; Farmacología; Química Analítica; Citología e Histología Normal y Patológica
Inflammatory bowel disease (IBD) is a complex condition that is influenced by numerous factors, including genetic, immune and environmental factors. In the search for new therapies, nutritional interventions including dietary polyphenols are becoming increasingly important in the management of IBD. The present study aimed to investigate the antioxidant and anti-inflammatory effects of commercial freeze-dried beer, an interesting product resulting from the fermentation of cereals, rich in polyphenols, in (I) an in vitro model of inflammation using lipopolysaccharide (LPS)-stimulated THP-1 human derived macrophages and (II) a murine dextran sodium sulfate (DSS)-induced chronic colitis model, for elucidating the action mechanism involved. According to the results, commercial freeze-dried beer exhibits antioxidant, anti-inflammatory and immunomodulatory properties in LPS-stimulated THP-1 human macrophages by reducing reactive oxygen species (ROS), tumor necrosis factor (TNF)-α and interleukin (IL)-6 levels. Moreover, in vivo results showed that preventive treatment with dietary freeze-dried beer improved murine DSS-induced chronic colitis by attenuation of the clinical and histological signs of colonic damage. Colonic cytokine levels in animals fed with commercial freeze-dried beer reached values near basal levels. In addition, pro-inflammatory cyclooxygenase (COX)-2 and microsomal prostaglandin E synthase (mPGES)-1 protein expressions were significantly downregulated via inhibition of nuclear transcription factor kappa B (NF-κB) translocation. This inhibition may be mediated by an induction of the antioxidant nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway and a reduction of signal transducer and activator of transcription (STAT)-3 phosphorylation orchestrating its potent anti-inflammatory and immunomodulatory effects. Overall, our results suggest that dealcoholized beer may be effective in the management of immune-mediated inflammatory diseases in which macrophages are crucial, including IBD, providing clues for developing useful dietary interventions against inflammation-associated pathologies.
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; Medicina; Farmacología; 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.
Exploring the Broad-spectrum Activity of Carbohydrate-based Iberin Analogues: From Anticancer Effect to Antioxidant Properties
(Elsevier, 2025) Prieto Ramírez, Luis Alberto; Khiar Fernández, N.; Calderón Montaño, José Manuel; López Lázaro, Miguel; Lucía Tamudo, J.; Nogueira, J. J.; León, R.; Moreno Rodríguez, Nazaret; Valdivia Giménez, Victoria Esther; Recio Jiménez, Rocío; Fernández Fernández, Inmaculada; Química Orgánica y Farmacéutica; Farmacología; Ministerio de Ciencia e Innovación (MICIN). España; Universidad de Sevilla
Iberin is a lower homologue of sulforaphane (SFN) which has shown effectiveness in addressing various pathologies, including its anti-inflammatory properties, antitumor activity against various cancers, and antimicrobial effects. Building on this activity, a series of carbohydrate-based analogues of the natural isothiocyanate (ITC) iberin were synthesized, and their anticancer and antioxidant activities were evaluated. Cytotoxicity studies on three cancer cell lines using Resazurin assay demonstrated significant cytotoxic activity, particularly against bladder cancer. The sulfonyl derivatives exhibited the most potent effects, with IC50 values comparable to those of reference natural isothiocyanates (from 10 to 20 μM). Computational simulations support the hypothesis that carbohydrate-based ITCs can interact with STAT3's SH2 domain in a manner similar to SFN, laying the groundwork for their potential development as STAT3-targeted anticancer agents. The antioxidant potential of these compounds was assessed by their ability to activate the Nrf2 factor, yielding CD values (concentration required to double luciferase activity compared to basal conditions) between 1.55 and 10.36 μM, without cytotoxicity at these concentrations. Notably, the phenylsulfone derivative 22β displayed slightly higher or comparable antioxidant activity to that of natural isothiocyanates. Based on these findings, this phenylsulfone analogue was selected as the optimal compound due to its dual anticancer and antioxidant activities. An additional advantage of this carbohydrate-based ITC is that it is a solid compound, making it easier to handle than natural isothiocyanates, which are typically liquids.
Estudio cualitativo sobre la adopción y puesta en valor del modelo capacidad-motivación-oportunidad de atención farmacéutica en las consultas externas de farmacia en España
(Elsevier, 2025-04-01) Álvarez Díaz, Ana María; Crespo Diz, Carlos; Monte Boquet, Emilio; Marcos Rodríguez, José Antonio; Margusino Framinan, Luis; Sánchez Yañez, Elena; Morillo Verdugo, Ramón Alejandro; Farmacología
Objetivo analizar y abordar las barreras que los servicios de farmacia se encuentran en el momento de la adopción del modelo de atención farmacéutica capacidad-motivación-oportunidad (CMO) en consultas externas, identificando los actores relevantes en el ecosistema, así como las motivaciones. Por último, realizar un primer acercamiento a soluciones que nos ayuden a seleccionar las que podrían llevarse a desarrollo a través de iniciativas futuras. Método se desarrolló una metodología estructurada en varias fases, incluyendo la formación de 2 equipos de trabajo: el «Equipo Rector», compuesto por farmacéuticos hospitalarios con experiencia en atención farmacéutica y humanización asistencial, y el «Equipo Core», integrado por profesionales de diversas disciplinas. La primera fase consistió en la realización de un taller de prospección online para explorar las fases de adopción del modelo. Posteriormente, se realizaron entrevistas semiestructuradas a actores clave (médicos, gerentes y asociaciones de pacientes) para identificar necesidades y barreras. Finalmente, se realizó un taller presencial que facilitó la ideación de soluciones y validación de propuestas. Resultados se identificaron 3 categorías de actores en el ecosistema del modelo CMO: agentes interesados (beneficiarios), agentes interesantes (influenciadores) y agentes ejecutivos (implementadores). Se evidenciaron diversas barreras, como la variabilidad en la infraestructura, la falta de interés de los gestores y la sobrecarga laboral de los farmacéuticos. No obstante, se observó una creciente motivación por parte de los profesionales y organizaciones para adoptar el modelo. Durante el taller de ideación se priorizaron 10 iniciativas, que incluyeron el uso de tecnologías digitales y programas de formación continua. Conclusión se destaca el alto potencial del modelo CMO para mejorar la atención farmacéutica en consultas externas de farmacia hospitalaria en España, a pesar de las barreras existentes. Las estrategias propuestas, centradas en la digitalización y la colaboración multidisciplinar, son clave para su implementación efectiva. Se sugiere la necesidad de futuras investigaciones para evaluar el impacto a largo plazo de estas iniciativas y fortalecer la implicación de asociaciones de pacientes y otros actores en el proceso de adopción.
Influence of antiretroviral therapy on frailty among people living with HIV
(Nature Research, 2025-04-25) Contreras Macías, Enrique; Robustillo Cortés, María de las Aguas; Morillo Verdugo, Ramón Alejandro; Farmacología
The aim of this study is to determine the influence of ARV on the diagnosis of frailty in PLWH. A single-centre prospective observational study was conducted involving PLWH over 18 years old who attended a hospital pharmacy outpatient service between January 2010 and December 2021. Participants were assessed for frailty using the Fried Frailty Phenotype scale and for geriatric syndromes including falls, cognitive impairment, depression, polypharmacy, and risk of malnutrition. ARV regimens were categorized by drug classes and the number of drugs. Associations between ARV and frailty were evaluated using multivariate logistic regression model. 729 PLWH were included, median age of 52 years. Frailty was observed in 15.6% of the participants, with an additional 48.4% classified as pre-frail. Comorbidities were present in 51.7%, with cardiovascular diseases being the most common. Geriatric syndromes were prevalent in 17.1% of the participants, with polypharmacy noted in 15.2%. the study concludes that while specific ARV regimens do not directly influence frailty development in PLWH, prolonged ARV exposure and polypharmacy significantly increase frailty risk. These findings highlight the need for comprehensive management strategies that optimize ARV regimens and minimize polypharmacy to improve the prognosis and quality of life for aging PLWH.
Impact of training healthcare professionals in the detection and management of neuropsychiatric comorbidities in people with HIV: The CONECTAR project in Spain
(Wiley, 2025-02-24) Blanch, Jordi; Martínez, Esteban; Mena, Álvaro; Dueñas, Carlos; Bernal, Enrique; Cabello, Alfonso; Morillo Verdugo, Ramón Alejandro; Pérez Valero, Ignacio; Farmacología
Introduction Although anxiety, depression and insomnia in people with HIV (PWH) are prevalent and have a major impact on clinical outcomes and quality of life, physicians fail to evaluate them routinely. The CONECTAR Project [Neuropsychiatric Comorbidity (NPC): Key to Antiretroviral Treatment] aimed to improve NPC clinical care in PWH in Spain by upskilling healthcare professionals (HCPs). Methods A group of HCPs developed a training programme, supported by national and international guidelines, to improve expertise on detecting and managing NPCs in PWH. The programme was conducted through workshops for physicians and nurses in various Spanish regions from April to November 2023; survey questionnaires were administered to physicians before the commencement of training and 15 days after. Later, a workshop was held for nurses who manage NPCs in PWH. Results The programme was completed by 64 physicians (22 had completed both questionnaires) and 11 nurses (no feedback obtained). Feedback from physicians reflected that the programme boosted awareness and self-perception of being more qualified, knowledgeable and able to use management tools and resources. Physicians also reported improved perception of time available for visits and more frequent enquiries about patients' NPC symptoms. Despite their satisfaction with the workshops, half of the physicians recognized the need for more training. Conclusion The CONECTAR Project was a successful training programme that was well received and valued by HCPs who routinely manage NPCs in PWH. Institutions involved in HCP training to manage anxiety, depression and insomnia more effectively in PWH should consider similar proposals to reinforce clinical practices.
Factors Associated with Adequate Quality of Life Levels in HIV Patients During a Five-Year Longitudinal Study
(Sociedad Española de Quimioterapia, 2025-04-16) Contreras Macías, Enrique; Morillo Verdugo, Ramón Alejandro; Farmacología
Introduction: Advances in antiretroviral therapy (ARV) have improved the life expectancy of people living with HIV (PLWH), shifting the focus to quality of life (QoL). However, aging, polypharmacy, and comorbidities pose challenges. This study aimed to evaluate the evolution of QoL over five years and identify associated sociodemographic, clinical, and pharmacotherapeutic factors. Methods: A single-center retrospective observational study was conducted in PLWH attending a tertiary hospital outpatient pharmacy. QoL was assessed using the EQ-5D-5L questionnaire. Sociodemographic, clinical, and pharmacotherapeutic variables—including age, polypharmacy, comorbidities, and Medication Regimen Complexity Index (MRCI)—were analyzed. Multivariate logistic regression identified predictors of good QoL, defined as a Visual Analogue Scale (VAS) score ≥76. Results: A total of 437 PLWH were included with median age 52 years. The participants were majority male (82.8%). Throughout the study, mean VAS scores remained stable, with 63.7–73.4% of participants reporting good QoL each year. The most frequently reported issues were related to mobility (8.9%), pain/discomfort (5.1%), and anxiety/depression (3.0%). Multivariate analysis showed that advanced age (OR: 1.55, 95%CI: 1.14–2.11), polypharmacy (OR: 1.87, 95%CI: 1.35–2.59), comorbidities (OR: 2.13, 95%CI: 1.76–2.89), and socioeconomic problems (OR: 2.47, 95%CI: 1.44–4.21) were significantly associated with lower QoL. Conclusion: Aging, polypharmacy, and socioeconomic disparities significantly impact QoL in PLWH. Integrating QoL assessments into routine care and addressing these factors through comprehensive management strategies could enhance long-term well-being.
Effects of dietary fats (fish, olive and high-oleic-acid sunflower oils) on lipid composition and antioxidant enzymes in rat liver
(Cambridge University Press, 1999) Ruiz Gutiérrez, Valentina; Pérez Espinosa, Alonso; Vázquez Cueto, Carmen María; Santa-María Pérez, Consuelo; Farmacología; Comisión Interministerial de Ciencia y Tecnología (CICYT). España
The effects of two oleic-acid-rich diets (containing olive oil, OO, and high-oleic-acid sunflower oil, HOSO) on plasma and liver lipid composition detoxification enzyme activities, were compared with those of a fish-oil (FO) diet and a control diet. Compared with the control diet, plasma and hepatic total triacylglycerol concentrations were increased in the animals fed on the HOSO and OO diets and decreased in those fed on the FO diet. The animals fed on FO showed the highest level of cholesterol in the liver and had lower plasma cholesterol concentrations when compared with those fed on the two oleic-acid-rich diets. In comparison with the animals fed on the diets enriched in oleic acid, the FO group showed higher hepatic levels of polyunsaturated fatty acids of the n-3 series and lower levels of fatty acids of the n-6 series. Livers of FO-fed rats, compared with those of OO- and HOSO-fed rats showed: (1) significantly higher activities of catalase (EC 1.11.1.6) glutathione peroxidase (EC 1.11.1.9) and Cu/Zn superoxide dismutase (EC 1.15.1.1); (2) no differences in the NADPH-cytochrome c reductase (EC 1.6.99.3) activity. The HOSO diet had a similar effect on liver antioxidant enzyme activities as the OO diet. In conclusion, it appears that changes in the liver fatty acid composition due mainly to n-3 lipids may enhance the efficiency of the antioxidant defence system. The two monounsaturated fatty acids oils studied (OO and HOSO), with the same high content of oleic acid but different contents of natural antioxidants, had similar effects on the antioxidant enzyme activities measured.
Effects of dietary oleic-rich oils (virgin olive and high-oleic-acid sunflower) on vascular reactivity in Wistar-Kyoto and spontaneously hypertensive rats
(Cambridge University Press, 2001) Herrera González, María Dolores; Pérez Guerrero, María Concepción; Marhuenda Requena, Elisa; Ruiz Gutiérrez, Valentina; Comisión Interministerial de Ciencia y Tecnología (CICYT). España
The effects of two monounsaturated fatty acid (MUFA)-rich diets, containing virgin olive oil (OO) and high-oleic-acid sunflower oil (HOSO), on development of vascular response from isolated thoracic rat aorta and lipid composition and fatty acid composition were studied and compared with samples from rats fed on a control diet. Dietary MUFA oils were fed for 6 weeks to spontaneously hypertensive (SHR) and Wistar–Kyoto (WKY) rats from 4 weeks of age. The maximum contraction of aortic ring preparations in response to phenylephrine (10-6 M) WAS SIGNIFICANTLY DECREASED IN SHR RATS FED WITH OO (0·81 (sem 0·05) v. 1·18 (sem 0·09) g, P<0·01) and treatment with HOSO did not alter the phenylephrine-induced contractions. The relaxant responses to acetylcholine (10-5 m) were significantly enhanced (30·03 (sem 0·70) v. 18·47 (sem 0·28) %, P<0·001) in the rings from SHR rats treated with OO, and were more pronounced than in WKY rats (P<0·05). In the same way, OO attenuated the dose–response curves induced by phenylephrine (10-8–10-5 m) from SHR rats, accompained with a slower contraction. These results suggest that only the chronic feeding of OO diet was able to attenuate the vascular response of rat aorta. In addition, an increase in phospholipid content (186·7 (sd 3·2) v. 159·1 (sd 11·3) g/kg, P<0·01) and changes in the fatty acid composition of aorta (mainly a decrease in arachidonic acid) could contribute to improving endothelial function. Therefore, the effects can not be attributed exclusively to the content of MUFA (mainly oleic acid). Other components of OO, such as polyphenols, not present in HOSO, may help to explain the vascular protective effect of OO consumption.

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