Farmacología

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

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5-Aza-2'-deoxycytidine causes replication lesions that require Fanconi anemia-dependent homologous recombination for repair
(Oxford University Press, 2013) Orta Vázquez, Manuel Luis; Calderón Montaño, José Manuel; Domínguez García, Inmaculada; Pastor Carrillo, Nuria María; Burgos Morón, Estefanía; López Lázaro, Miguel; Cortés, Felipe; Mateos Cordero, Santiago; Helleday, Thomas; Universidad de Sevilla. Departamento de Biología Celular; Universidad de Sevilla. Departamento de Farmacología; Ministerio de Educación y Ciencia (MEC). España; Junta de Andalucía
5-Aza-2'-deoxycytidine (5-azadC) is a DNA methyltransferase (DNMT) inhibitor increasingly used in treatments of hematological diseases and works by being incorporated into DNA and trapping DNMT. It is unclear what DNA lesions are caused by 5-azadC and if such are substrates for DNA repair. Here, we identify that 5-azadC induces DNA damage as measured by γ-H2AX and 53BP1 foci. Furthermore, 5-azadC induces radial chromosomes and chromatid breaks that depend on active replication, which altogether suggest that trapped DNMT collapses oncoming replication forks into double-strand breaks. We demonstrate that RAD51-mediated homologous recombination (HR) is activated to repair 5-azadC collapsed replication forks. Fanconi anemia (FA) is a rare autosomal recessive disorder, and deaths are often associated with leukemia. Here, we show that FANCG-deficient cells fail to trigger HR-mediated repair of 5-azadC-induced lesions, leading to accumulation of chromatid breaks and inter-chromosomal radial fusions as well as hypersensitivity to the cytotoxic effects of 5-azadC. These data demonstrate that the FA pathway is important to protect from 5-azadC-induced toxicity. Altogether, our data demonstrate that cytotoxicity of the epigenetic drug 5-azadC can, at least in part, be explained by collapsed replication forks requiring FA-mediated HR for repair.
9-PAHPA long term intake in DIO and db/db mice ameliorates insulin sensitivity but has few effects on obesity and associated metabolic disorders
(Elsevier, 2023) Bonafos, Béatrice; Cortés Espinar, Antonio J.; Balas, Laurence; Pessemesse, Laurence; Lambert, Karen; Benlebna, Melha; Gaillet, Sylvie; Ávila Román, Francisco Javier; Feillet-Coudray, Christine; Universidad de Sevilla. Departamento de Farmacología
Branched fatty acid esters of hydroxy fatty acids are endogenous lipids reported to have antidiabetic and anti-inflammatory effects. Recently, we showed that 9-palmitic acid esters of hydroxypalmitic acid (9-PAHPA) and 9-oleic acid esters of hydroxypalmitic acid increased insulin sensitivity in mice when incorporated to a chow diet or to a high fat and high sucrose diet. However, preventive supplementation with 9-PAHPA and 9-oleic acid esters of hydroxypalmitic acid in high fat and high sucrose diet mice did not impair significant weight gain or the development of hyperglycemia. The aim of this work was therefore to study whether in two animal models of obesity, namely the classical diet-induced obesity (DIO) and the db/db mice, 9-PAHPA may have beneficial effects against obesity and liver and skeletal muscle metabolic dysfunction. In DIO mice, we observed that 9-PAHPA increased body weight and fat mass. In line with this observation, we found that 9-PAHPA supplementation decreased energy expenditure. In liver and in skeletal muscle, mitochondrial activities and oxidative stress parameters were not modified by 9-PAHPA supplementation. In db/db mice, 9-PAHPA had no effect on the dramatic weight gain and hyperglycemia. In addition, 9-PAHPA supplementation did not correct either the hepatomegaly and hepatic steatosis or the severe muscle atrophy recorded compared with db/+ animals. Likewise, supplementation with 9-PAHPA did not impact the different metabolic parameters analyzed, either in the liver or in the skeletal muscles. However, it decreased insulin resistance in DIO and db/db mice. In conclusion, our study indicated that a long-term intake of 9-PAHPA in DIO and db/db mice improved insulin sensitivity but had only few effects on obesity and associated metabolic disorders.
A hydroalcoholic extract from the leaves of Nerium oleander inhibits glycolysis and induces selective killing of lung cancer cells
(Georg Thieme Verlag, 2013) Calderón Montaño, José Manuel; Burgos Morón, Estefanía; Orta Vázquez, Manuel Luis; Mateos Cordero, Santiago; López Lázaro, Miguel; Universidad de Sevilla. Departamento de Biología Celular; Universidad de Sevilla. Departamento de Farmacología
Recent evidence suggests that cardiac glycosides might be used for the treatment of cancer. The ornamental shrub Nerium oleander has been used in traditional medicine for treating several disorders including cancer, and extracts from the leaves of this plant have already entered phase I clinical trials. In this communication, we have prepared a hydroalcoholic extract from the leaves of Nerium oleander (containing 4.75 ± 0.32 % of cardenolides) and have assessed its cytotoxic activity in A549 lung cancer cells vs. MRC5 nonmalignant lung fibroblasts. The results showed that the cytotoxicity of the Nerium oleander extract against the cancer cell line was significantly higher than that against the nonmalignant cell line, with a potency and selectivity similar to those of the anticancer drug cisplatin. Pretreatment of A549 cells with the antioxidants N-acetylcysteine and catalase slightly prevented the cytotoxicity of the extract, therefore suggesting that the formation of reactive oxygen species participates in its cytotoxic activity but does not play a major role. Nerium oleander extract-induced cytotoxicity and DNA damage (gamma-H2AX focus formation) were slightly higher in cells lacking BRCA2 (deficient in homologous recombination repair) than in parental cells; this indicates that the induction of DNA damage may also play a role in the cytotoxicity of the extract. Nerium oleander extract induced a marked inhibition of glycolysis (glucose consumption and lactate production) in A549 cells, comparable to that of the glycolysis inhibitor dichloroacetate (currently in clinical development for cancer therapy). Because platinum compounds are widely used in the treatment of lung cancer, we tested the cytotoxicity of several combinations of cisplatin with the extract and found a moderate synergism when Nerium oleander extract was administered after cisplatin but a moderate antagonism when it was added before cisplatin. Our results suggest that extracts from Nerium oleander might induce anticancer effects in patients with lung cancer and support their possible advancement into phase II clinical trials for the treatment of this type of cancer.
A local mechanism by which alcohol consumption causes cancer
(2016) López Lázaro, Miguel; Universidad de Sevilla. Departamento de Farmacología
Epidemiological data indicate that 5.8% of cancer deaths world-wide are attributable to alcohol consumption. The risk of cancer is higher in tissues in closest contact on ingestion of alcohol, such as the oral cavity, pharynx and esophagus. However, since ethanol is not mutagenic and the carcinogenic metabolite of ethanol (acetaldehyde) is mostly produced in the liver, it is not clear why alcohol use preferentially exerts a local carcinogenic effect. It is well known that ethanol causes cell death at the concentrations present in alcoholic beverages; however, this effect may have been overlooked because dead cells cannot give rise to cancer. Here I discuss that the cytotoxic effect of ethanol on the cells lining the oral cavity, pharynx and esophagus activates the division of the stem cells located in deeper layers of the mucosa to replace the dead cells. Every time stem cells divide, they become exposed to unavoidable errors associated with cell division (e.g., mutations arising during DNA replication and chromosomal alterations occurring during mitosis) and also become highly vulnerable to the genotoxic activity of DNA-damaging agents (e.g., acetaldehyde and tobacco carcinogens). Alcohol consumption may increase the risk of developing cancer of the oral cavity, pharynx and esophagus by promoting the accumulation of cell divisions in the stem cells that maintain these tissues in homeostasis. Understanding the mechanisms of carcinogenicity of alcohol is important to reinforce the epidemiological evidence and to raise public awareness of the strong link between alcohol consumption and cancer
A New Peracetylated Oleuropein Derivative Ameliorates Joint Inflammation and Destruction in a Murine Collagen-Induced Arthritis Model via Activation of the Nrf-2/Ho-1 Antioxidant Pathway and Suppression of MAPKs and NF-κB Activation
(MDPI, 2021-01) Castejón Martínez, María Luisa; Alarcón de la Lastra Romero, Catalina; Rosillo Ramírez, María de los Ángeles; Montoya García, Tatiana; Fernández-Bolaños Guzmán, José María; González Benjumea, Alejandro; Sánchez Hidalgo, Marina; Universidad de Sevilla. Departamento de Farmacología; Universidad de Sevilla. Departamento de Ingeniería Química; Ministerio de Economía y Competitividad (MINECO). España; Dirección General de Investigación (DGI). España; Junta de Andalucía; European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER); Universidad de Sevilla; Universidad de Sevilla. CTS259: Farmacología Experimental y Farmacia Clínica; Universidad de Sevilla. FQM134: Química Fina de Carbohidratos
Oleuropein (OL), an olive tree secoiridoid and its peracetylated derivate (Per-OL) haveexhibited several beneficial effects on LPS-stimulated macrophages and murine experimental sys-temic lupus erythematosus (SLE). This study was designed to evaluate dietary Per-OL in comparisonwith OL supplementation effects on collagen-induced arthritis (CIA) murine model. Three-weeks-old DBA-1/J male mice were fed from weaning with a standard commercial diet or experimentalenriched-diets in 0.05 % (w/w) OL, 0.05% and 0.025% Per-OL. After six weeks of pre-treatment, arthri-tis was induced by bovine collagen type II by tail base injection (day 0) and on day 21, mice received abooster injection. Mice were sacrificed 42 days after the first immunization. Both Per-OL and OL dietssignificantly prevented histological damage and arthritic score development, although no statisticallysignificant differences were observed between both compounds. Also, serum collagen oligomericmatrix protein (COMP), metalloprotease (MMP)-3 and pro-inflammatory cytokines levels were ame-liorated in paws from secoiridoids fed animals. Mitogen-activated protein kinases (MAPK)s andnuclear transcription factor-kappa-B (NF-κB) activations were drastically down-regulated whereasnuclear factor E2-related factor 2 (Nrf2) and heme-oxygenase-1 (HO-1) protein expressions wereup-regulated in those mice fed with OL and Per-OL diets. We conclude that both Per-OL and itsparent compound, OL, supplements might provide a basis for developing a new dietary strategy forthe prevention of rheumatoid arthritis.
A new view of carcinogenesis and an alternative approach to cancer therapy
(2010) López Lázaro, Miguel
Abrupt Photoperiod Changes Differentially Modulate Hepatic Antioxidant Response in Healthy and Obese Rats: Effects of Grape Seed Proanthocyanidin Extract (GSPE)
(MDPI, 2023-12-02) Cortés Espinar, Antonio J.; Ibarz Blanch, Néstor; Soliz Rueda, Jorge R.; Calvo, Enrique; Bravo, Francisca Isabel; Mulero, Miquel; Ávila Román, Francisco Javier; Universidad de Sevilla. Departamento de Farmacología; Ministerio de Ciencia e Innovación (MICIN). España; Agencia Estatal de Investigación. España; European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER)
Disruptions of the light/dark cycle and unhealthy diets can promote misalignment of biological rhythms and metabolic alterations, ultimately leading to an oxidative stress condition. Grape seed proanthocyanidin extract (GSPE), which possesses antioxidant properties, has demonstrated its beneficial effects in metabolic-associated diseases and its potential role in modulating circadian disruptions. Therefore, this study aimed to assess the impact of GSPE administration on the liver oxidant system of healthy and diet-induced obese rats undergoing a sudden photoperiod shift. To this end, forty-eight photoperiod-sensitive Fischer 344/IcoCrl rats were fed either a standard (STD) or a cafeteria diet (CAF) for 6 weeks. A week before euthanizing, rats were abruptly transferred from a standard photoperiod of 12 h of light/day (L12) to either a short (6 h light/day, L6) or a long photoperiod (18 h light/day, L18) while receiving a daily oral dose of vehicle (VH) or GSPE (25 mg/kg). Alterations in body weight gain, serum and liver biochemical parameters, antioxidant gene and protein expression, and antioxidant metabolites were observed. Interestingly, GSPE partially ameliorated these effects by reducing the oxidative stress status in L6 through an increase in GPx1 expression and in hepatic antioxidant metabolites and in L18 by increasing the NRF2/KEAP1/ARE pathway, thereby showing potential in the treatment of circadian-related disorders by increasing the hepatic antioxidant response in a photoperiod-dependent manner.
Acción de los hormonas sexuales. Sobre el cociente lipoprotéinico beta/alfa en los enfermos arterioesclerosos
(1960-10-30) Tallón Cantero, Rodrigo; Sánchez de la Cuesta y Gutiérrez, Gabriel; Universidad de Sevilla. Departamento de Farmacología
Ácidos grasos poliinsaturados de microalgas inhiben la producción de TNF-a en células THP-1 y reducen la inflamación intestinal en un estudio animal
(Sociedad Española de Farmacología : Fundación Teófilo Hernando, 2012) Ávila Román, Francisco Javier; Domínguez, C.; Talero Barrientos, Elena Mª; Reyes, Carolina de los; Ortega, M. J.; Zubía, Eva; García-Mauriño Ruiz-Berdejo, Sofía; Motilva Sánchez, Virginia; Universidad de Sevilla. Departamento de Biología Vegetal y Ecología; Universidad de Sevilla. Departamento de Farmacología
Active involvement of the general public in pharmacovigilance
(2020-02-12) Romao Matos, Cristiano Filipe; Hunsel, Florence van; Álvarez de Sotomayor Paz, María; Universidad de Sevilla. Departamento de Farmacología
The importance of direct patient reporting has been highlighted by recent European legislation on pharmacovigilance, and in addition, there is also an increasing attention worldwide for this subject. In Europe, the legislation directs member states to take all appropriate measures to encourage patients to report suspected adverse drug reactions (ADR) to the relevant national authorities. The introduction of patient reporting in pharmacovigilance indicates a change in attitude in which patient reporting is valued due to their potential to contribute useful information on drug safety. The aim of this project is to give a better understanding of the role of patients in pharmacovigilance systems. The chosen approach during this project intended to lead to a better understanding of the awareness and perception of the risk involved with medicine use and how patients and healthcare professionals can contribute to optimize the current pharmacovigilance system. For the purpose of this study, the project was divided in several parts, for which specific objectives were designed and described below, together with main results of the thesis. The first study described in Chapter 2 discusses the experiences of patient reporting to pharmacovigilance in Portugal and quantifies consumers motivation for reporting ADRs, investigating patient opinions about reporting with a quantitative analysis in a large group of consumers. The objective was to describe the attitudes and knowledge of the general public regarding spontaneous reporting and the reasons and opinions that can influence consumers adverse drug reaction underreporting. The study reveals that consumers are more likely to do spontaneous report about severe reactions or if they are worried about the symptoms. Also, more altruistic motives as the contribution to research and knowledge, the contribution to improvement of drugs and prevent harm to other people are seen as motives to report ADRs by patients. These motives can be classified in reporting for oneself (severity, worried, problems), reporting for others (share experiences, preventing harm, feeling responsible) or reporting for improvement (research and knowledge, patient information leaflet). It appeared that multiple patient characteristics (gender, age and level of education) had an effect on the motives of patients to report their ADR. In Chapter 3 were described the attitudes toward patient reporting systems, and progress toward implementing such systems among national competent authorities participating in the World Health Organization Programme for International Drug Monitoring. The study shows that most countries accept ADR reports from patients by an official reporting system designed for patients or through the existing system for Healthcare Professionals (HCPs). The main reasons for not having a Patient Reporting System (PRS) are financial restraints and a lack of information/education of patients. Attitudes toward a PRS are positive, but some countries fear 181 that they will not be able to handle an increase in reports. Most countries accept ADR reports from the general public. The lack of resources/budget and the lack of information/education for patients are highlighted as the major obstacles to the implementation of PRS. Chapter 4 focused on patient organizations role to promote patient reporting. In Chapter 4.1, it was studied the role of European patient organizations with the objective of understand the role of European patient organizations as stakeholders to optimize patient involvement in pharmacovigilance. There is a wide range of interest in drug safety issues among patient organizations, which appear to have an important role in encouraging patients to talk with their doctors/pharmacists about ADRs experienced, or to help him/her report the ADRs to the pharmacovigilance systems. A lack of resources, budget, and support from National Competent Authorities (NCAs) are seen as the main barriers to being involved in pharmacovigilance. On the other hand, an important part of the organizations appears to not have any activities or involvement related to pharmacovigilance. Bringing pharmacovigilance stakeholders and patient organizations together could create a more optimal patient reporting culture. Members of a patient organization showed more positive opinions related to pharmacovigilance. They would like to have more information about ADRs related to their medication and a higher intention to have information on how to report when compared to other patients. The other study in Chapter 4 described medicines and attitudes and opinions regarding pharmacovigilance in people with diabetes. The study explored the impact of the patient reports being followed by a patient diabetes association. The objective was to assess risk perception of developing adverse drug reactions and knowledge, attitudes and opinions regarding pharmacovigilance in patients with diabetes and to investigate whether being a member of a patient organization for diabetes had an effect on these factors. Patients followed in a diabetes patient association presented a higher score of risk perception, experiences using the medicines, but also by the information received from the patient organization. Being a member of a patient organization seems to have an important role in increasing risk perception since they presented the highest risk perception scores for medicines related to their disease. Those patients affirmed that their doctor explained the possible ADRs of their medication and they have higher intention to report ADRs in the future if they are serious or unexpected. Patient organizations are well positioned to be a source where patients can obtain reliable information, changing their attitudes and perceptions about the disease and drug treatments. An additional chapter was provided, related with HCPs role as active agents to improve the involvement of patients in pharmacovigilance. Chapter 5.1 objective was to describe the attitudes and knowledge of different community pharmacy professional groups regarding the spontaneous reporting of adverse drug reactions to identify the factors that can influence adverse drug reaction under-reporting. Despite HCPs knowledge of the pharmacovigilance system, only a small 182 percentage of Community pharmacy professionals had reported ADRs, and approximately half did not usually encourage consumers to report possible ADRs. In Chapter 5.2, the objective was to evaluate community pharmacy professionals as role players . Reporting of ADRs is fundamental to pharmacovigilance, and consumer reporting is a significant contribution to creating useful information on drug safety. Community pharmacy professionals can play a major role in pharmacovigilance by reporting ADRs directly or encouraging consumers to report them. Measures to overcome under-reporting as encouraging HCPs and consumers to play an active role in pharmacovigilance, namely continuous education and training should be incorporated to increase the level of risk perception and encourage a better attitude about reporting for both HCPs and consumers. Chapter 6 presents a general discussion about the role of general public in pharmacovigilance, providing recommendations that arose from the results with different points of view of patient participation in pharmacovigilance (national competent authorities, HCPs, patient organizations and patients themselves). In conclusion, this thesis has focused on an overview of the participation of different stakeholders in pharmacovigilance, including HCPs, NCAs, Patient Organizations and patients themselves. Further research and developments for pharmacovigilance systems and for patients themselves arose from the results provided.
Actividad citotóxica de la fracción de acetato de etilo de un extracto obtenido de Viscum cruciatum Sieber
(Oficina Española de Patentes y Marcas (OEPM), 2007-10-22) Martín Cordero, Carmen; Pedraza Cerbán, Mª Ángeles; Gálvez Peralta, Marina; López Lázaro, Miguel; Ayuso González, Mª Jesús; Universidad de Sevilla. Departamento de Farmacología
Actividad citotóxica de la fracción de acetato de etilo de un extracto obtenido de Viscum cruciatum Sieber. La presente invención tiene por objeto a un extracto de Viscum cruciatum Sieber, con actividad citotóxica, así como a los principios activos aislados que son venenos de topoisomerasa II, las composiciones farmacológicas que contienen tanto al extracto como a los principios activos aislados de ésta y al uso de estas composiciones en la preparación de un medicamento para el tratamiento del cáncer. La presente invención tiene su aplicación en el campo de la medicina.
Actividad farmacológica de Cecropia obtusifolia. Bertol
(1999) Ortiz Castillo, Rafael; Herrera González, María Dolores; Pérez Guerrero, María Concepción; Universidad de Sevilla. Departamento de Farmacología, Pediatría y Radiología
Actividad farmacológica de la fracción de esteroles y alcoholes triterpenicos aislada del aceite de oliva virgen.
(1997) Ruiz Gutiérrez, Valentina; Puerta Vázquez, Rocío de la; Maestro Durán, Roberto; Universidad de Sevilla. Departamento de Farmacología
Actualización 2022 de los indicadores para la calidad asistencial y la atención farmacéutica a las personas que viven con el virus de la inmunodeficiencia humana
(Elsevier, 2023-06) Martín Conde, María Teresa; Monte Boquet, Emilio; Navarro Aznares, Herminia; Robustillo Cortés, María de las Aguas; Rodríguez González, Carmen; Serrano López de las Hazas, Joaquín Ignacio; Morillo Verdugo, Ramón Alejandro; Universidad de Sevilla. Departamento de Farmacología
Objetivo actualizar y definir los indicadores para la mejora de la calidad asistencial y la atención farmacéutica a las personas que viven con infección por VIH en España. Método el presente proyecto, que actualiza la versión anterior del documento de 2013, se desarrolló en 4 fases de trabajo realizadas entre enero y junio de 2022. En la fase 1, de organización, se creó un grupo de trabajo conformado por 7 especialistas en farmacia hospitalaria con amplia experiencia en atención farmacéutica y procedentes de distintos servicios del territorio nacional. Adicionalmente otros 34 especialistas, participaron en la valoración de los indicadores a través de 2 rondas de evaluación online para generación del consenso. Para la fase 2, inicialmente, se llevó a cabo una revisión bibliográfica con el objetivo de establecer una base a partir de la cual poder definir una propuesta de criterios de calidad e indicadores. A continuación, se realizó una propuesta preliminar de criterios y se establecieron revisiones para su ajuste en varias reuniones de trabajo telemáticas. En la fase 3 se estableció el consenso basado en la metodología de consenso Delphi-Rand/UCLA. Adicionalmente todos los indicadores clasificados como adecuados y necesarios fueron agrupados según 2 niveles de recomendación de monitorización, de manera que pueda orientar a los servicios en la prioridad de su medición: claves y avanzados. Por último, en la fase 4 se elaboró el documento final del proyecto, junto con las fichas descriptivas correspondientes para cada indicador con la finalidad de facilitar su medición y evaluación por parte de los servicios de farmacia hospitalaria. Resultados se obtuvo un listado consensuado de ítems conformado por 79 indicadores adecuados y necesarios que permiten establecer un seguimiento y monitorización de la calidad y actividad de la atención farmacéutica a las personas que viven con VIH. De los mismos, 60 fueron establecidos como clave y 19 avanzados. Conclusiones los indicadores definidos y actualizados, desde la versión anterior de 2013, pretenden ser una herramienta para los profesionales para orientar la toma de decisiones y facilitar la medición y valoración de los aspectos más relevantes de la calidad y atención farmacéutica de las personas que viven con infección por VIH.
Adecuación del tratamiento farmacológico en pacientes pluripatológicos
(Elsevier, 2013) Galván Banqueri, Mercedes; Santos Ramos, Bernardo; Vega Coca, María Dolores; Alfaro Lara, Eva Rocío; Nieto Martín, María Dolores; Pérez Guerrero, María Concepción; Universidad de Sevilla. Departamento de Farmacología
Objetivo: Identificar herramientas de medida de la adecuación del tratamiento farmacológico de utilidad en el paciente pluripatológico (PP). Dise˜no: Revisión sistemática. Fuentes de datos: Se consultaron las siguientes bases de datos (diciembre de 2009): Pubmed, EMBASE, CINAHL, PsycINFO e Índice Médico Espa˜nol para detectar herramientas de medida de la adecuación del tratamiento en pacientes pluripatológicos o, en su defecto, ancianos o polimedicados. Selección de estudios: Se incluyeron estudios tanto con metodología cualitativa como cuantitativa, tanto trabajos teóricos como de campo, ya fuesen originales o revisiones, y se incluyeron trabajos de todos los ámbitos del sistema sanitario. Se recuperaron 108 artículos, de los que se seleccionaron 39. La consulta de sus referencias bibliográficas permitió incorporar 20 trabajos más, en total 59 artículos. Extracción de datos: De entre todas las herramientas detectadas, fueron seleccionadas aquellas con posible utilidad para el paciente pluripatológico. Se clasificaron los métodos en implícitos y explícitos y se tabularon las características de los trabajos de campo. Resultados: Se identificaron 2 métodos implícitos (MAI y Hamdy) y 6 métodos explícitos (criterios Beers, IPET, STOPP/START, ACOVE, CRIME y NORGEP). Ninguno era específico para pluripatológicos. El cuestionario MAI, los criterios Beers y sus modificaciones son los más usados en la literatura médica. Las ventajas de los criterios explícitos hacen que muchos de ellos se hayan desarrollado recientemente. Conclusiones: Existen diversas herramientas para la medida de la adecuación y, sin embargo, ninguna de ellas ha sido dise˜nada para una población de PP, que por sus características diferenciales requiere un abordaje específico.
Adherence to disease-modifying treatments in patients with multiple sclerosis in spain
(Dove Press, 2019) Morillo Verdugo, Ramón Alejandro; Ramírez Herráiz, Esther; Fernández Del Olmo, Raquel; Roig Bonet, Montserrat; Valdivia García, María; Universidad de Sevilla. Departamento de Farmacología
Purpose: Adherence to disease-modifying treatments is essential in order to maximize the beneficial effects of treatment for multiple sclerosis (MS). There are numerous treatments that have been approved. Treatment selection is essential in patient adherence. In addition, patient preference plays an increasingly significant role in treatment decision-making. This study aims to evaluate the degree of adherence, along with other variables that may influence this adherence, in Spain. Methods: A cross-sectional study was conducted with 157 MS patients with disease-modifying treatments. Adherence was assessed using the Morisky Green scale, and other related factors were measured using a questionnaire that addressed demographics, disease characteristics, global perception of pathology, impact of medication on patient’s life, and treatment decision-making. Results: The adherence rate was 71% and was associated with the following variables: older age, more treatments received, time to diagnosis 5–10 years, absence of exacerbations, better cognitive status, being married/in a union, clear information about the disease, and higher treatment satisfaction. The main cause for non-compliance was forgetfulness (27%). Conclusion: The adherence rate is acceptable. It is widely known that treatment satisfaction is related to adherence. In our study, patients’ level of satisfaction was higher with oral treatments. However, oral administration showed a greater lack of adherence. The main cause of lack of adherence was forgetfulness. In relation to other variables, cognitive status and family support showed a correlation with treatment adherence.
Administration of L-arginine reduces the delay of the healing process caused by Ibuprofen. Implication of COX and growth factors expression
(Histology and Histopathology, 2005) Sánchez Fidalgo, Susana; Martín Lacave, Inés María; Illanes, Matilde; Bruseghini, Leo; Esteras, Antonio; Motilva Sánchez, Virginia; Universidad de Sevilla. Departamento de Farmacología
The objective of the present study has been to advance knowledge of the gastric role played by the amino acid L-Arginine (L-Arg) in the evolution of a chronic gastric ulcer. In order to clarify it, L-Arg alone or together with Ibuprofen have been administrated in an experimental acetic acid chronic ulcer, analysing characteristic parameters of an active curative process, such as PGE2 production, COX expression, and also angiogenesis, proliferation/apoptosis and growth factors expression. Our results reveal that L-Arg is favourable in the healing process improving the curative course. Ibuprofen caused a delay in ulcer healing, more evident 14 days after ulcer induction; COX-2 expression was increased at the 7th day although no signal of protein could be detected after 14 days; PGE2 production was inhibited in intact and ulcerated areas at both times assayed. In contrast, treatment with L-Arg reduced the delay of the lesion, the increment in COX-2 expression induced by Ibuprofen, and was able to maintain PGE2 levels similar to the control group after 14 days. Additionally, the histological study showed that the healing effects of L-Arg might be associated with an increased angiogenesis and FGF-2 expression. These actions could be considered key factors in the healing response associated with L-Arg administration. However, the proliferation study assayed with the PCNA-immunostaining method did not reveal significant differences, as the same as the apoptosis analysis. In conclusion, the coupling of L-Arg to Ibuprofen is an attractive alternative to Ibuprofen administration alone because it not only attenuates but also improves the evolution of chronic lesions through mechanisms that implicate endogenous PG and FGF-2-associated pathways, which allow an increase of angiogenesis process.
Adrenomedullin in inflammatory process associated with experimental pulmonary fibrosis
(2011) Motilva Sánchez, Virginia; Di Paola, Rosanna; Talero Barrientos, Elena Mª; Mazzon, Emanuela; Cuzzocrea, Salvatore; Bramanti, Placido; Galuppo, María; Universidad de Sevilla. Departamento de Farmacología
Adsorción de pesticidas en organoarcillas: posibilidades de su uso en formulaciones de liberación controlada
(2000-07-26) Carrizosa Vila, María José; Hermosín Gaviño, María del Carmen; Universidad de Sevilla. Departamento de Farmacología
Se han preparado una serie de organoarcillas a partir de arcillas naturales con distintas cargas laminares y capacidades de cambio, organoacationes y grados de saturación en los mismos, en base a su posible utilización como barreras de contaminación por inmovilización de pesticidas de características diversas, asi como su empleo en preparaciones de liberacion controlada que permitan una dosis de biodisponibilidad concordante con el poder asimilatorio de la planta y evitando altos indices de contaminación. Los sistema se han caracterizado mediante tecnicas de adsorcion-desorcion utilizando tecnicas de analisis como hplc, centelleo liquido, difraccion de rayos x y espectroscopia infrarroja. Se han realizado estudios de retencion y movilidad en columnas de suelo, asi como bioensayos. Los resultados han permitido diseñar, con resultados aceptablemente buenos, organoarcillas que pueden ser utilizadas tanto como barreras descontaminantes como en formulaciones de liberación controlada.
Age-related changes in melatonin synthesis in rat extrapineal tissues
(Elsevier, 2009-05) Sánchez Hidalgo, Marina; Alarcón de la Lastra Romero, Catalina; Carrascosa Salmoral, María del Pilar; Naranjo Gutiérrez, María del Carmen; Gómez Corbera, Araceli; Guerrero, Juan M.; Universidad de Sevilla. Departamento de Farmacología; Universidad de Sevilla. Departamento de Bioquímica Médica y Biología Molecular e Inmunología; Junta de Andalucía; Ministerio de Ciencia e Innovación (MICIN). España
In the search of new therapeutic targets improving the quality of life of elderly, melatonin, “the chemical expression of darkness”, seems to play a remarkable role in aging process possibly due to its antioxidant, immunoenhancer and anti-aging properties. The present study was designed to elucidate effects of aging in melatonin extrapineal synthesis and investigate evident age-related alterations in the action mechanisms involved. The presence of the two key enzymes involved in melatonin synthesis, arylalkylamine-N-acetyltransferase (AA-NAT) and hydroxyindole-O-methyltransferase (HIOMT) was analyzed in thymus, spleen, liver, kidney and heart of 3- and 12 month-old rats using real time PCR as well as its functionality by enzymatic activity assays. In addition, extrapineal melatonin content was measured by a competitive enzyme immunoassay (ELISA). The results of this study reveal that all rat tissues studied including thymus, and for the first time, spleen, liver, kidney and heart have the necessary machinery to synthesize melatonin. Moreover, we report an age-related decline in rat extrapineal melatonin synthesis with a consequent HIOMT functionality decrease in spleen, liver and heart during physiological aging. On the contrary, NAT enzymatic activity maintains unchanged without evident alterations with advancing age. Moreover, diminished melatonin concentrations were measured in these tissues cited above during aging except in the thymus, where, surprisingly, melatonin content, NAT/HIOMT expression, and enzymatic functionality assays revealed no significant alterations with age. As a conclusion, we report evident age-related changes in melatonin synthesis in some rat peripheral organs. We suggest that thymus may develop compensatory mechanisms to counteract the loss of immune activity and consequently, the loss of this potent antioxidant, during physiological aging.

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