Artículos (Farmacología, Pediatría y Radiología)

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Actualización en el manejo de la Bronquiolitis
(Sociedad de Pediatria de Andalucía Occidental y Extremadura, 2011-10) Borja Urbano, G.; Pérez Pérez, Guadalupe María; Andrés Martín, Anselmo; Navarro Merino, Martín; Universidad de Sevilla. Departamento de Farmacología, Pediatría y Radiología
La bronquiolitis aguda (BA) es una entidad clínica de importancia en pediatría, representando la principal causa de ingreso por infección respiratoria aguda de vías aéreas inferiores en el niño menor de 2 años y una de las causas más importantes de morbilidad infantil. Aunque su etiología es variada el virus respiratorio sincitial es el más relevante, llegando a causar hasta el 80% de los casos de BA. Sus manifestaciones clínicas son muy similares al asma, siendo difícil el diagnóstico diferencial con esta entidad. Es de suma importancia una adecuada valoración de la gravedad clínica del paciente mediante escalas específicas para ello así como el conocimiento de la rentabilidad de las pruebas diagnósticas para conseguir una relación riesgo-beneficio adecuada. Actualmente el tratamiento con broncodilatadores ó adrenalina asociados a suero fisiológico hipertónico parece la terapia más adecuada, siendo retirado si no se objetiva mejoría clínica. El Palivizumab es un fármaco útil en la profilaxis de la BA en niños de riesgo.
El prematuro con enfermedad pulmonar crónica/displasia broncopulmonar: seguimiento
(Elsevier Doyma, 2011-03) Pérez Pérez, Guadalupe María; Navarro Merino, Martín; Andrés Martín, Anselmo; Universidad de Sevilla. Departamento de Farmacología, Pediatría y Radiología
Malformación Adenomatoidea Quística Pulmonar. Presentación de un caso en un lactante con crecimiento rápido de la lesión.
(Sociedad de Pediatria de Andalucía Occidental y Extremadura, 2011-10) Borja Urbano, G.; Pérez Pérez, Guadalupe María; Andrés Martín, Anselmo; González González, J.; Navarro Merino, Martín; Universidad de Sevilla. Departamento de Farmacología, Pediatría y Radiología
La malformación adenomatoidea quística es una entidad poco frecuente producida por una anomalía en el desarrollo de la vía aérea. Forma parte de las denominadas malformaciones de las vías aéreas pulmonares (MCVAP), que engloba 5 tipos de malformaciones dependiendo del tamaño de la lesión quística y su aspecto morfológico. Actualmente se diagnostica mediante ecografía prenatal. Las manifestaciones clínicas son muy variadas, pudiéndose mostrar desde lesiones asintomáticas a otras con importante distrés respiratorio. Existe controversia en cuanto a las indicaciones de cirugía de las lesiones asintomáticas de pequeño tamaño. Presentamos un caso clínico de un niño de 4 años de edad intervenido de una malformación adenomatoidea quística pulmonar tipo 1 a los 2 meses de edad. El interés de nuestro caso radica en el crecimiento tan rápido de la lesión que condicionó que la cirugía se realizase de forma urgente.
Neonatal screening for spinal muscular atrophy and severe T-and B-cell lymphopenias in Andalusia: a prospective study
(MDPI, 2025-01-28) De Felipe, Beatriz; Delgado-Pecellin, Carmen; Lopez-Lobato, Mercedes; Olbrich, Peter; Blanco Lobo, Pilar; Márquez-Fernández, Josefina; Salamanca, Carmen; Madruga-Garrido, Marcos; Neth, Olaf; Universidad de Sevilla. Departamento de Farmacología, Pediatría y Radiología
Spinal muscular atrophy (SMA) and severe T- and/or B-cell lymphopenias (STBCL) in the form of severe combined immunodeficiencies (SCID) or X-linked agammaglobulinemia (XLA) are rare but potentially fatal pathologies. In January 2021, we initiated the first pilot study in Spain to evaluate the efficacy of a very early detection technique for SMA and SCID. RT–PCR was performed on prospectively collected dried blood spots (DBSs) from newborns in Western Andalusia (Spain). Internal and external controls (SCID, XLA and SMA) were included. The determination of SMA was relative (positive/negative) and that of TRECs and KRECs was quantitative (copies/punch). A total of 14.035 prospective samples were analysed. All controls were correctly identified while no cases of SMA or SCID/XLA were prospectively identified. DBS analysis of infants with suspected SMA or STBCL that presented to our centre showed pathological values in two cases each for SMA and SCID and one for XLA, all of them being subsequently confirmed genetically. In this prospective pilot study, no infants with SMA or STBCL were detected; however, the technique applied here was shown to be reliable and fast, further supporting the benefits and need to include SMA and SCID in national newborn screening (NBS) programs, as it will allow early supportive and curative therapy.
Differential clinical characteristics and prognosis of intraventricular conduction defects in patients with chronic heart failure
(Wiley, 2013-03-19) Cinca, Juan; Méndez, Ana; Puig, Teresa; Ferrero, Andreu; Roig, Eulalia; Vázquez, Rafael; González Juanatey, José R.; Alonso-Pulpón, Luis; Delgado, Juan; Brugada Terradellas, Josep; Pascual Figal, Domingo; Fernández Palacín, Ana; Miñano Sánchez, Javier; Universidad de Sevilla. Departamento de Medicina Preventiva y Salud Pública; Universidad de Sevilla. Departamento de Farmacología, Pediatría y Radiología; European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER); Instituto de Salud Carlos III
Aims Intraventricular conduction defects (IVCDs) can impair prognosis of heart failure (HF), but their specific impact is not well established. This study aimed to analyse the clinical profile and outcomes of HF patients with LBBB, right bundle branch block (RBBB), left anterior fascicular block (LAFB), and no IVCDs. Methods and results Clinical variables and outcomes after a median follow-up of 21 months were analysed in 1762 patients with chronic HF and LBBB (n = 532), RBBB (n = 134), LAFB (n = 154), and no IVCDs (n = 942). LBBB was associated with more marked LV dilation, depressed LVEF, and mitral valve regurgitation. Patients with RBBB presented overt signs of congestive HF and depressed right ventricular motion. The LAFB group presented intermediate clinical characteristics, and patients with no IVCDs were more often women with less enlarged left ventricles and less depressed LVEF. Death occurred in 332 patients (interannual mortality = 10.8%): cardiovascular in 257, extravascular in 61, and of unknown origin in 14 patients. Cardiac death occurred in 230 (pump failure in 171 and sudden death in 59). An adjusted Cox model showed higher risk of cardiac death and pump failure death in the LBBB and RBBB than in the LAFB and the no IVCD groups. Conclusion LBBB and RBBB are associated with different clinical profiles and both are independent predictors of increased risk of cardiac death in patients with HF. A more favourable prognosis was observed in patients with LAFB and in those free of IVCDs. Further research in HF patients with RBBB is warranted.
Development of an expert-based scoring system for early identification of patients with inborn errors of immunity in primary care settings – the PIDCAP project
(Springer, 2025) Rivière, Jacques G.; Carot-Sans, Gerard; Piera-Jiménez, Jordi; de la Torre, Sergi; Santos Pérez, Juan Luis; Rodrigo, Carlos; Olbrich, Peter; Soler-Palacin, Pere; Universidad de Sevilla. Departamento de Farmacología, Pediatría y Radiología
Early diagnosis of inborn errors of immunity (IEIs) has been shown to reduce mortality, morbidity, and healthcare costs. The need for early diagnosis has led to the development of computational tools that trigger earlier clinical suspicion by physicians. Primary care professionals serve as the first line for improving early diagnosis. To this end, a computer-based tool (based on extended Jeffrey Modell Foundation (JMF) Warning Signs) was developed to assist physicians with diagnosis decisions for IEIs in the primary care setting. Two expert-guided scoring systems (one pediatric, one adult) were developed. IEI warning signs were identified and a panel of 36 experts reached a consensus on which signs to include and how they should be weighted. The resulting scoring system was tested against a retrospective registry of patients with confirmed IEI using primary care EHRs. A pilot study to assess the feasibility of implementation in primary care was conducted. The scoring system includes 27 warning signs for pediatric patients and 24 for adults, adding additional clinically relevant criteria established by expert consensus to the JMF Warning Signs. Cytopenias, ≥ 2 systemic infections, recurrent fever and bronchiectasis were the leading warning signs in children, as bronchiectasis, autoimmune diseases, cytopenias, and > 3 pneumonias were in adults. The PIDCAP (Primary Immune Deficiency “Centre d’Atenció Primària” that stands for Primary Care Center in Catalan) tool was implemented in the primary care workstation in a pilot area. The expert-based approach has the potential to lessen under-reporting and minimize diagnostic delays of IEIs. It can be seamlessly integrated into clinical primary care workstations.
Comparative efficacy of leniolisib (CDZ173) versus standard of care on rates of respiratory tract infection and serum immunoglobulin M (IgM) levels among individuals with activated phosphoinositide 3-kinase delta (PI3Kδ) syndrome (APDS): an externally controlled study
(Wiley, 2025-01-01) Whalen, John; Chandra, Anita; Kracker, Sven; Ehl, Stephan; Seidel, Markus G.; Gulas, Ioana; Olbrich, Peter; Körholz, Julia; Universidad de Sevilla. Departamento de Farmacología, Pediatría y Radiología
Leniolisib, an oral, targeted phosphoinositide 3-kinase delta (PI3Kδ) inhibitor, was well-tolerated and efficacious versus placebo in treating individuals with activated PI3Kδ syndrome (APDS), an ultra-rare inborn error of immunity (IEI), in a 12-week randomised controlled trial. However, longer-term comparative data versus standard of care are lacking. This externally controlled study compared the long-term effects of leniolisib on annual rate of respiratory tract infections and change in serum immunoglobulin M (IgM) levels versus current standard of care, using data from the leniolisib single-arm open-label extension study 2201E1 (NCT02859727) and the European Society for Immunodeficiencies (ESID) registry. The endpoints were chosen following feasibility assessment considering comparability and availability of data from both sources. Baseline characteristics between groups were balanced through inverse probability of treatment weighting. The leniolisib-treated group included 37 participants, with 62 and 49 participants in the control group for the respiratory tract infections and serum IgM analyses, respectively. Significant reductions in the annual rate of respiratory tract infections (rate ratio: 0.34; 95% confidence interval [CI]: 0.19, 0.59) and serum IgM levels (treatment effect: -1.09 g/L; 95% CI: -1.78, -0.39, P = 0.002) were observed in leniolisib-treated individuals versus standard of care. The results were consistent across all sensitivity analyses, regardless of censoring, baseline infection rate definition, missing data handling, or covariate selection. These novel data provide an extended comparison of leniolisib treatment versus standard of care, highlighting the potential for leniolisib to deliver long-term benefits by restoring immune system function and reducing infection rate, potentially reducing complications and treatment burden.
Clinical practice update of antifungal prophylaxis in immunocompromised children
(Sociedad Española de Quimioterapia, 2019-10) Ramos Amador, José Tomas; Alba Romero, Concepción; Belda Hofheinz, Sylvia; Candel, Francisco Javier; Carazo Gallego, Begoña; Fernández Polo, Aurora; Olbrich, Peter; Soler-Palacín, Pere; Universidad de Sevilla. Departamento de Farmacología, Pediatría y Radiología
Due to the rise in the number and types of immunosuppressed patients, invasive fungal infections (IFI) are an increasing and major cause of morbidity and mortality in immunocompromised adults and children. There is a broad group of pediatric patients at risk for IFI in whom primary and/or secondary antifungal prophylaxis (AFP) should be considered despite scant evidence. Pediatric groups at risk for IFI includes extremely premature infants in some settings, while in high-risk children with cancer receiving chemotherapy or undergoing haematopoietic stem cell transplantation (HCT), AFP against yeast and moulds is usually recommended. For solid organ transplanted, children, prophylaxis depends on the type of transplant and associated risk factors. In children with primary or acquired immunodeficiency such as HIV or long-term immunosuppressive treatment, AFP depends on the type of immunodeficiency and the degree of immunosuppression. Chronic granulomatous disease is associated with a particular high-risk of IFI and anti-mould prophylaxis is always indicated. In contrast, AFP is not generally recommended in children with long stay in intensive care units. The choice of AFP is limited by the approval of antifungal agents in different age groups and by their pharmacokinetics characteristics. This document aims to review current available information on AFP in children and to provide a comprehensive proposal for each type of patient.
Evaluation of immunomodulatory properties of phenolic extracts from olive mill by-products using Caco-2 cells and molecular docking analysis
(Elsevier, 2024-12) Barrera Chamorro, Luna; Fernández Prior, África; González de la Rosa, Teresa; Rivero Pino, Fernando; Claro Cala, Carmen María; Montserrat de la Paz, Sergio; Universidad de Sevilla. Departamento de Bioquímica Médica y Biología Molecular e Inmunología; Universidad de Sevilla. Departamento de Farmacología, Pediatría y Radiología; Ministerio de Ciencia, Innovación y Universidades (MICIU). España; European Union (UE); Universidad de Sevilla. CTS1074: Inmunonutrición e Inmunometabolismo
The bioactive potential of phenolic extracts derived from olive mill solid by-product (OMSbP), also called alperujo, and olive mill water (OMW), remains a topic of significant interest due to the amount of these, espe- cially in Mediterranean regions, and their potential health benefits. In this study, the antioxidant and immu- nomodulatory properties of phenolic extracts obtained from OMSbP and OMW (OMSbP-P and OMW-P, respectively) in intestinal cells were evaluated. Initially, phenol-rich extracts were prepared by ethanol/ethyl acetate extraction and were characterized by HPLC-DAD analyses. The in vitro antioxidant activity showed potent bioactivities for all extracts evaluated. Toxicity assays did not reveal adverse effects on Caco-2 cell viability at concentrations relevant to immunomodulatory activity. Subsequently, the immunomodulatory effects of these extracts were assessed by measuring gene expression of pro- and anti-inflammatory cytokines. The results demonstrate that both OMSbP-P and OMW-P exhibit significant immunomodulatory activities, as evidenced by modulated cytokine gene expression in intestinal cells. Furthermore, molecular docking analyses of the identified phenols with the TLR4/MD2 receptor showed binding affinity, increasing the evidence that these extracts could exert immunomodulatory activity. Overall, our findings suggest that OMSbP-P and OMW-P possess promising immunomodulatory properties in intestinal cells, thus emphasizing their potential as natural therapeutic agents for managing immune-related disorders and promoting gut health. Further elucidation of the molecular mech- anisms underlying these effects and in vivo studies are warranted to fully exploit the therapeutic potential of these extracts.
Water-soluble rice bran enzymatic extract attenuates dyslipidemia, hypertension and insulin resistance in obese Zucker rats
(Springer, 2013) Justo Gómez, María Luisa; Rodríguez Rodríguez, Rosalía; Claro Cala, Carmen María; Álvarez de Sotomayor Paz, María; Parrado Rubio, Juan; Herrera González, María Dolores; Universidad de Sevilla. Departamento de Farmacología, Pediatría y Radiología; Universidad de Sevilla. Departamento de Farmacología; Universidad de Sevilla. Departamento de Bioquímica y Biología Molecular; Universidad de Sevilla. Instituto de Biomedicina de Sevilla (IBIS); Gobierno de España; Ministerio de Ciencia Y Tecnología (MCYT). España; Universidad de Sevilla. CTS1074: InmunoNutrición e InmunoMetabolismo; Universidad de Sevilla. CTS178: Farmacología Cardiovascular; Universidad de Sevilla. AGR212: Tecnología y Aplicación de Enzimas
Background and purpose: Rice bran enzymatic extract (RBEE) has advantages compared to the original rice bran or its oils including water solubility, lack of rancidity and increased content in high nutritional proteins and nutraceutical compounds, particularly phytosterols, γ-oryzanol and tocols. Our aim was to determine the beneficial effects of RBEE in the pathogenesis of metabolic syndrome in obese Zucker rats. Methods: Obese Zucker rats and their lean littermates were fed a 1 and 5 % RBEE-supplemented diet (O1, O5, L1 and L5). Simultaneously, obese and lean Zucker rats, fed a standard diet, were used as controls (OC and LC, respectively). Body weight, food and water intake, and systolic blood pressure were weekly evaluated. After treatment, biochemical assays of serum glucose, insulin, triglycerides (TG), total cholesterol (TC), non-esterified fatty acids (NEFA), adiponectin and nitrates (NO(x)) were determined. Results: RBEE treatment reduced circulating levels of TG and TC, whereas increased HDL-cholesterol without altering NEFA values in obese rats. The extract also induced a significant dose-dependent reduction of hypertension linked to obesity. RBEE of 5 % improved insulin resistance and subsequently reduced HOMA-IR index without altering serum glucose levels. Obese animals treated with RBEE showed partial restoration of adiponectin levels and a significant attenuation of pro-inflammatory values of NO(x). Conclusion: These findings evidence the nutraceutical properties of RBEE against the pathogenesis of metabolic syndrome by attenuating dyslipidemia, hypertension and insulin resistance as well as by restoring hypoadiponectinemia associated to obesity.
Structural, mechanical and myogenic properties of small mesenteric arteries from ApoE KO mice: Characterization and effects of virgin olive oil diets
(Elsevier, 2015-01) Ogalla, Elena; Claro Cala, Carmen María; Álvarez de Sotomayor Paz, María; Herrera González, María Dolores; Rodríguez Rodríguez, Rosalía; Universidad de Sevilla. Departamento de Farmacología, Pediatría y Radiología; Universidad de Sevilla. Departamento de Farmacología; Universidad de Sevilla. Instituto de Biomedicina de Sevilla (IBIS); Ministerio de Ciencia e Innovación (MICIN). España; Universidad de Sevilla. CTS1074: InmunoNutrición e InmunoMetabolismo; Universidad de Sevilla. CTS178: Farmacología Cardiovascular
Objective: We analyzed the structural, mechanical, myogenic and functional properties of resistance arteries of ApoE KO compared to wild type (WT) mice. We also determined the influence of saturated fat in comparison to virgin olive oil-enriched diets in vascular wall abnormalities. Methods: Male ApoE KO (ApoE) and WT mice (8-weeks-old) were assigned to the groups: standard chow diet (SD), high fat diet (HFD), virgin olive oil (VOO) and high polyphenol-VOO-enriched diet (Oleaster®) (OT) (15% w/w). After 20 weeks, structural, mechanical and myogenic properties of isolated small mesenteric arteries (SMA) were analyzed by pressure myography. For functional studies, vasodilatation to acetylcholine was assessed. Arterial superoxide anion production was measured by ethidium fluorescence. Results: Hypertrophic remodeling and distensibility in ApoE KO SMA was lower compared to WT mice, suggesting an alteration in the autoregulation mechanisms aimed to compensate disease progression. However, ApoE deficiency resulted in a lower impairment in myogenic tone in response to intraluminal pressure, in addition to an improved endothelium-dependent hyperpolarizing vasodilatation. Also, we evidenced the beneficial effects of VOO in contrast to a saturated fat-enriched diet on SMA wall disorders. Only the endothelial function improvement induced by olive oil was dependent on polyphenols content. Conclusion: Resistance arteries structure, mechanic, myogenic and functional responses from ApoE KO mice significantly differ from WT mice, evidencing the influence of the type of diet on these disorders. These results are particularly useful to determine the contribution of resistance arteries during the atherosclerotic process and to provide novel insights into the Mediterranean dietary pattern to reduce the burden of atherosclerotic disease.
Rice bran prevents high-fat diet-induced inflammation and macrophage content in adipose tissue
(Springer, 2016) Justo, Maria Luisa; Claro Cala, Carmen María; Zeyda, Maximilian; Stulnig, Thomas M.; Herrera González, María Dolores; Rodríguez-Rodríguez, Rosalía; Universidad de Sevilla. Departamento de Farmacología, Pediatría y Radiología; Universidad de Sevilla. Departamento de Farmacología
Background The inflammatory process associated with obesity mainly arises from white adipose tissue (WAT) alterations. In the last few years, nutritional-based strategies have been positioned as promising alternatives to pharmacological approaches against these pathologies. Our aim was to determine the potential of a rice bran enzymatic extract (RBEE)-supplemented diet in the prevention of metabolic, biochemical and functional adipose tissue and macrophage changes associated with a diet-induced obesity (DIO) in mice. Methods C57BL/6J mice were fed high-fat diet (HF), 1 and 5 % RBEE-supplemented high-fat diet (HF1 % and HF5 %, respectively) and standard diet as control. Serum cardiometabolic parameters, adipocytes size and mRNA expression of pro-inflammatory biomarkers and macrophage polarization-related genes from WAT and liver were evaluated. Results RBEE administration significantly decreased insulin resistance in obese mice. Serum triglycerides, total cholesterol, glucose, insulin, adiponectin and nitrites from treated mice were partially restored, mainly by 1 % RBEE-enriched diet. The incremented adipocytes size observed in HF group was reduced by RBEE treatment, being 1 % more effective than 5 % RBEE. Pro-inflammatory biomarkers in WAT such as IL-6 and IL-1β were significantly decreased in RBEE-treated mice. Adiponectin, PPARγ, TNF-α, Emr1 or M1/M2 levels were significantly restored in WAT from HF1 % compared to HF mice. Conclusions RBEE-supplemented diet attenuated insulin resistance, dyslipidemia and morphological and functional alterations of adipose tissue in DIO mice. These benefits were accompanied by a modulating effect in adipocytes secretion and some biomarkers associated with macrophage polarization. Therefore, RBEE may be considered an alternative nutritional complement over metabolic syndrome and its complications.
Drug diffusion from disperse systems with a hydrophobically modified polysaccharide: Enhancer (R) vs Franz cells
(Elsevier Science Ltd, 2012-09-13) Lucero Muñoz, María Jesús; Claro Cala, Carmen María; Casas Delgado, Marta; Jiménez-Castellanos Ballesteros, María Rosa; Universidad de Sevilla. Departamento de Farmacología, Pediatría y Radiología; Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica
This study assesses the capacity of a new hydrophobically modified polysaccharide –hydroxypropyl cellulose–methyl methacrylate – to control drug release in semisolid formulations. The dispersed sys tems contain the new polymer, Igepal®CO520 as surfactant and theophylline as model drug at three concentrations (0.5, 1 and 1.5%, w/w). Drug release study shows that the systems containing 0.5% (w/w) of drug have faster release and higher diffusion coefficient than the other two concentrations. These results can be explained by two different structures (“relaxed” and “structured”) found from a rheologi cal point of view. Also, this paper compares two different devices for testing drug release and diffusion. It has been obtained more reliable and reproducible results with Enhancer Cell®respect to Franz diffusion cell. In both cases, Fickian diffusion was the mechanism predominant for all systems. Finally, the utility of this polymer has been demonstrated to make three-dimensional gel structure and control theophylline release from systems in topical application.
Unsaponifiable and phenolic fractions from virgin olive oil prevent neuroinflammation skewing microglia polarization toward M2 phenotype
(Elsevier, 2019-11) Toscano Sánchez, María del Rocío; Millán Linares, María del Carmen; Naranjo, María C.; Lemus Conejo, Ana; Claro Cala, Carmen María; Montserrat de la Paz, Sergio; Universidad de Sevilla. Departamento de Farmacología, Pediatría y Radiología; Universidad de Sevilla. Departamento de Bioquímica Médica y Biología Molecular e Inmunología; Universidad de Sevilla
Inhibiting M1 microglia phenotype while stimulating M2 microglia phenotype has been suggested as potential therapeutic approach for the treatment of neuroinflammation-related diseases. Our aim was to evaluate the anti-neuroinflammatory effects of minor compounds found in unsaponifiable fraction (UF) and in phenolic fraction (PF) of virgin olive oil (VOO) in BV-2 microglial cells and in brain of mice with high-fat diet (HFD)-induced obesity by RT-qPCR, ELISA and flow cytometry techniques. We observed that UF and PF enhance M2 microglia polarization, whereas LPS polarized microglia prone to M1 phenotype. In addition, in contrast to dietary SFAs, dietary VOO primed for a reduced pro-inflammatory profile in the brain of mice. These findings unveil a potential beneficial role for minor compounds of VOO in regulating the plasticity of microglia. These exciting findings open opportunities for developing nutraceutical strategies with olive oil as principal source of fat to prevent development and progression of neuroinflammation-related diseases.
Microvascular disorders in obese Zucker rats are restored by a rice bran diet
(Elsevier, 2014-05) Claro Cala, Carmen María; Vila, Elisabet; Herrera González, María Dolores; Rodríguez Rodríguez , Rosalía; Universidad de Sevilla. Departamento de Farmacología, Pediatría y Radiología; Universidad de Sevilla. Departamento de Farmacología; Universidad de Sevilla. Instituto de Biomedicina de Sevilla (IBIS); Gobierno de España; Ministerio de Ciencia e Innovación (MICIN). España; Universidad de Sevilla. CTS1074: InmunoNutrición e InmunoMetabolismo; Universidad de Sevilla. CTS178: Farmacología Cardiovascular
Background and aim: Nutritional-based approaches aimed to prevent microvascular dysfunction associated to obesity present potential advantages over pharmacological strategies. Our aim was to test whether a rice bran enzymatic extract (RBEE)-supplemented diet could attenuate microvascular alterations in obese rats. Methods and results: Lean and obese Zucker rats were fed standard diet supplemented or not with 1% and 5% RBEE for 20 weeks. Functional studies were performed in small mesenteric arteries in isometric myograph. Immunoblotting and fluorescence studies were made in arterial homogenates and arterial sections, respectively. RBEE-supplementation restored microvascular function in obese rats through a marked increase in NO and endothelial-derived hyperpolarizing factor contribution by up-regulation of eNOS and calcium-activated potassium channels expression, respectively, in association to a substantial reduction of microvascular inflammation and superoxide anion formation. These data agrees with the beneficial actions of RBEE on dyslipidemia, hyperinsulinemia and hypertension in obesity. Conclusion: The multi-factorial properties of RBEE-diet, especially for restoring the function of small resistance arteries shows this dietary-based approach to be a promising candidate for prevention of microvascular alterations in obesity, which are crucial in cardiovascular events in obese subjects.
Monogenic early-onset lymphoproliferation and autoimmunity: natural history of STAT3 gain-of-function síndrome
(2023-04) Leiding, Jennifer W.; Vogel, Tiphanie P.; Santarlas, Valentine G.J.; Mhaskar, Rahul; Smith, Madison R.; Carisey, Alexandre; Olbrich, Peter; Worth, Austen; Universidad de Sevilla. Departamento de Farmacología, Pediatría y Radiología
Background: In 2014, germline signal transducer and activator of transcription (STAT) 3 gain-of-function (GOF) mutations were first described to cause a novel multisystem disease of early-onset lymphoproliferation and autoimmunity. Objective: This pivotal cohort study defines the scope, natural history, treatment, and overall survival of a large global cohort of patients with pathogenic STAT3 GOF variants. Methods: We identified 191 patients from 33 countries with 72 unique mutations. Inclusion criteria included symptoms of immune dysregulation and a biochemically confirmed germline heterozygous GOF variant in STAT3. Results: Overall survival was 88%, median age at onset of symptoms was 2.3 years, and median age at diagnosis was 12 years. Immune dysregulatory features were present in all patients: lymphoproliferation was the most common manifestation (73%); increased frequencies of double-negative (CD4-CD8-) T cells were found in 83% of patients tested. Autoimmune cytopenias were the second most common clinical manifestation (67%), followed by growth delay, enteropathy, skin disease, pulmonary disease, endocrinopathy, arthritis, autoimmune hepatitis, neurologic disease, vasculopathy, renal disease, and malignancy. Infections were reported in 72% of the cohort. A cellular and humoral immunodeficiency was observed in 37% and 51% of patients, respectively. Clinical symptoms dramatically improved in patients treated with JAK inhibitors, while a variety of other immunomodulatory treatment modalities were less efficacious. Thus far, 23 patients have undergone bone marrow transplantation, with a 62% survival rate. Conclusion: STAT3 GOF patients present with a wide array of immune-mediated disease including lymphoproliferation, autoimmune cytopenias, and multisystem autoimmunity. Patient care tends to be siloed, without a clear treatment strategy. Thus, early identification and prompt treatment implementation are lifesaving for STAT3 GOF syndrome.
Endothelium-dependent vasodilator and antioxidant properties of a novel enzymatic extract of grape pomace from wine in dustrial waste
(Elsevier, 2012-12-01) Rodriguez-Rodriguez, Rosalia; Justo, Maria Luisa; Claro Cala, Carmen María; Vila, Elisabet; Parrado Rubio, Juan; Herrera González, María Dolores; Álvarez de Sotomayor Paz, María; Universidad de Sevilla. Departamento de Farmacología, Pediatría y Radiología; Universidad de Sevilla. Departamento de Bioquímica y Biología Molecular; Universidad de Sevilla. Departamento de Farmacología; Instituto de Biomedicina de Sevilla (IBIS); Ministerio de Ciencia e Innovación de España; Universidad de Sevilla. CTS-1074: Inmunonutrición e inmunometabolismo; Universidad de Sevilla. AGR-212 : Tecnologia y aplicacion de enzimas; Universidad de Sevilla. CTS-178: Farmacología cardiovascular
The aim of the present study was to evaluate the vascular effects of an enzymatic extract of grape pomace (GP-EE) on isolated arteries, focusing our attention on endothelium-derived relaxation and on its antioxidant properties. Grape pomace derived from wine making was extracted by an enzymatic process and its composition of polyphenols was evaluated by HPLC and ESI-MS/MS, detecting kaempferol, catechin, quercetin and procyanidins B1 and B2, trace levels of resveratrol and tracing out gallocatechin and anthocyanidins. GP-EE induced endothelium- and NO-dependent vasodilatation of both rat aorta and small mesenteric artery (SMA) segments and reduced Phe-induced response in aortic rings. Both ORAC and DPPH assays confirmed antioxidant scavenging properties of GP-EE, which also prevented O(2)(·-) production (assessed by DHE fluorescence) and contraction elicited by ET-1. These results provide evidence that GP-EE possesses interesting antioxidant and protective vascular properties and highlight the potential interest of this extract as a functional food.
Severe acute respiratory syndrome coronavirus 2 vaccination in children with a history of multisystem inflammatory syndrome in children: an international survey
(Elsevier, 2022) Hoste, Levi; Soriano-Arandes, Antoni; Buddingh, Emilie Pauline; Whittaker, Elizabeth; Belot, Alexandre; Ulloa-Gutiérrez, Rolando; Olbrich, Peter; Haerynck, Filomeen; Universidad de Sevilla. Departamento de Farmacología, Pediatría y Radiología
The optimal severe acute respiratory syndrome coronavirus 2 vaccine strategy for patients with a history of multisystem inflammatory syndrome in children (MIS-C) is unclear. We performed an international survey (32 countries) and found substantial variations in vaccine policies. Respondents did not report relapses of MIS-C or other severe inflammatory side effects after severe acute respiratory syndrome coronavirus 2 vaccination in 273 patients with a history of MIS-C.
Diagnostic and therapeutic challenges in a child with complete Interferon-γ Receptor 1 deficiency
(Wiley, 2015-07-14) Olbrich, Peter; Martínez Saavedra, María Teresa; Pérez Hurtado, José María; Sánchez, Cristina; Sánchez Sánchez, Berta; Deswarte, Caroline; Obando, Ignacio; Casanova, Jean-Laurent; Speckmann, Carsten; Bustamante, Jacinta; Rodríguez Gallego, Carlos; Neth, Olaf; Universidad de Sevilla. Departamento de Farmacología, Pediatría y Radiología
Autosomal recessive (AR) complete Interferon-γ Receptor1 (IFN-γR1) deficiency is a rare variant of Mendelian susceptibility to mycobacterial disease (MSMD). Although hematopoietic stem cell transplantation (HSCT) remains the only curative treatment, outcomes are heterogeneous; delayed engraftment and/or graft rejection being commonly observed. This case report and literature review expands the knowledge about this rare but potentially fatal pathology, providing details regarding diagnosis, antimicrobial treatment, transplant performance, and outcome that may help to guide physicians caring for patients with AR complete IFN-γR1 or IFN-γR2 deficiency
Association of human beta defensin 2 serum levels and sepsis in preterm neonates
(Lippincott williams & wilkins, 2013-10) Olbrich, Peter; Pavón, Antonio; Rosso, Maria Luisa; Molinos, Agueda; De Felipe, Beatriz; Sanchez, Berta; Praena Fernandez, Juan Manuel; Jimenez, Francisco; Obando Santaella, Ignacio; Neth, Olaf; Universidad de Sevilla. Departamento de Farmacología, Pediatría y Radiología
Objectives: To determine human beta-defensin-2 levels in term and preterm neonates at birth and to evaluate its impact on sepsis. Design: Observational study. Setting: Single tertiary care hospital. Patients: Term neonates and preterm neonates were recruited and divided in groups according to important clinical events. Interventions: Cord blood samples were drawn from all newborns immediately after birth. Human beta-defensin-2 levels were determined using enzyme-linked immunosorbent assay technology. All neonates were followed clinically during the first 30 days of life. Measurements and Main Results: Forty-two term and 31 preterm neonates were enrolled. Human beta-defensin-2 levels in term neonates were higher compared with preterm infants (median, 1,882 vs 918 pg/mL; p = 0.003) and correlated with gestational age and birth weight. Of 31 preterm neonates, seven suffered from late-onset sepsis, and this was associated with lower human beta-defensin-2 levels (median, 513 vs 1,411 pg/mL; p = 0.006). Conclusion: Preterm neonates show lower human beta-defensin-2 levels in cord blood compared with term neonates. Low human beta-defensin-2 levels in preterm neonates might be associated with an increased risk of late-onset sepsis.

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