Social cognition and emotional rehabilitation in participants with schizofrenia.

Introduction: People with schizophrenia have deficits in social cognition, emotion and social perception, as well as attributional style. The purpose of this study was to evaluate the efficacy of a multicomponent social cognition training program, e-Motional Training® (ET), in people with schizophrenia and to compare its efficacy with people who did not receive it. Therefore, a single-blind RCT was conducted in participants with a diagnosis of schizophrenia. Methods: A randomized, single-blind, clinical trial was conducted with 50 stable outparticipants with schizophrenia (registry number CHUC_2019_109). All participants (control and intervention) were treated with pharmacotherapy, case management and were on Individual Placement and Support methodology for competitive employment. The intervention group was treated with ET, an online program designed for social cognition rehabilitation. Pre and post assessment was performed using different battery of tests. General mixed models with subject identification and repeated measures over time were used. Results: Different pre and post measurements were performed in the two groups. No significant differences were found in sociodemographic characteristics between the control and intervention groups. Improvements were obtained in the intervention group in the Ekman test (p = 0.009), mainly enhanced by the improvement shown in three emotions: fear, sadness and disgust (p = 0.041, p = 0.021 and p = 0.038 respectively). Conclusion: ET is a promising online training tool for social cognition deficits in schizophrenia, in particular, for the improvement of emotions.Clinical Trial Registration: https://beta.clinicaltrials.gov, NCT05866328.

Impact of Frailty on Outcomes of First-Line Pembrolizumab Monotherapy in a Real-World Population with Advanced Non-Small Cell Lung Cancer.

ICIs have been able to improve overall survival in advanced-stage lung cancer. The benefit of this therapy is limited in patients with poor ECOG PS. However, this scale is imprecise and can be influenced by different factors, such as frailty. Cancer patients have a high risk of frailty independently of age. In this observational, single-center, retrospective study, we investigated the effect of frailty on the effectiveness of pembrolizumab in first-line use in a cohort of 101 patients with metastatic NSCLC. Frailty was determined using a frailty score system developed by Sakakida et al. Univariate and multivariate analysis was performed to determine the prognostic role of frailty on OS and PFS. Median OS was significantly higher in patients with low frailty compared with intermediate and high frailty (23.8 vs. 7.0 and 1.8 months, respectively; p < 0.001). Median PFS was also significantly higher in patients with low frailty compared with intermediate and high frailty (10.5 vs. 3.9 and 1.6 months; p < 0.001, respectively). Frailty was the only variable that showed significant differences in OS and PFS. Multivariate analysis confirms frailty as an independent predictor of OS and PFS. Frailty assessment could help to select which patients are candidates for ICIs in NSCLC.

Alfabetización en salud y COVID-19 en mayores: aproximación desde la Farmacia Comunitaria / Health literacy and COVID-19 in the elderly: approach from the Community Pharmacy

Introducción: La alfabetización en salud son las habilidades cognitivas y sociales que determinan que los individuos puedan acceder, entender y usar la información para promover y mantener su salud. La necesidad de estas habilidades ha sido notable en la pandemia. Método: Se realiza un cuestionario específico a los pacientes mayores de 60 años. Este consta de tres partes: el instrumento HLS-EU-Q16 adaptado a COVID-19, preguntas sobre la actuación del farma-céutico y la herramienta SAHLSA.Resultados: La población era mayoritariamente femenina (75,4%) y su edad era de 79,2±9,4 años. El nivel educativo mayoritario fue de educación primaria (34,4%), predominando éste y el sin estudios en mayores de 80 años. El cuestionario HLS-EU-Q16 reveló que la alfabetización en salud sobre COVID-19 era deficiente (23%), insuficiente (70,5%) y suficiente (6,6%). El cuestionario SAHLSA mostró alfabetización suficiente en el 80%. Mien-tras que el primer cuestionario no mostró relación con el nivel educativo, ningún bachiller o universita-rio presentó valores insuficientes en el cuestionario SAHLSA. Por último, los entrevistados consideraron como primer sanitario al que acudir para obtener información fiable al médico (77%), seguido por el farmacéutico (13%). El 75% consideró que el farmacéutico le había ayudado a comprender las precauciones frente a la COVID-19. Conclusiones: Los pacientes presentan dificul-tades para identificar la información fiable y para encontrar información de tratamientos frente a la COVID. Esta necesidad no está relacionada con el nivel educativo ni con la alfabetización en salud en otras áreas. El farmacéutico puede ser un agente clave en resolver esta necesidad. (AU)

Introduction: Health literacy is the degree to which individuals have the capacity to obtain, process, and understand basic health information and servi-ces needed to make appropriate health decisions. The need for such capacity has been notable during pandemic.Method: A specific questionnaire was made to patients older than 60 years. The questionnaire included the HLS-EU-Q16 instrument adapted to COVID-19, some questions about the role of phar-macists and the SAHLSA tool.Results: Most of the patients were women (75.4%) and the age was 79.2±9.4 years. The level of educa-tion of the majority was primary education (34.4%). Primary education and no schooling were the most common levels in older than 80 years. As HLS-EU-Q16 questionnaire showed, health literacy about COVID-19 was deficient (23%), insufficient (70,5%) and sufficient (6,6%). SAHLSA tool pointed out sufficient health literacy in 80%. The results of the first questionnaire were not related to the level of education. However, all participants with interme-diate or advanced education had sufficient marks in the SAHLSA tool. Finally, the responders considered physicians as the main health professional who can help them to obtain reliable information (77%), followed by pharmacists (13%). 75% of responders agreed that pharmacists helped them understand the measures against COVID-19. Conclusions: Patients have difficulties to identify reliable information and to find information about COVID treatments. This need is not related to the educational level or to the health literacy in other fields. Pharmacists may be a key agent to solve that need. (AU)

The cognitive and psychiatric subacute impairment in severe Covid-19.

Neurologic impairment persisting months after acute severe SARS-CoV-2 infection has been described because of several pathogenic mechanisms, including persistent systemic inflammation. The objective of this study is to analyze the selective involvement of the different cognitive domains and the existence of related biomarkers. Cross-sectional multicentric study of patients who survived severe infection with SARS-CoV-2 consecutively recruited between 90 and 120 days after hospital discharge. All patients underwent an exhaustive study of cognitive functions as well as plasma determination of pro-inflammatory, neurotrophic factors and light-chain neurofilaments. A principal component analysis extracted the main independent characteristics of the syndrome. 152 patients were recruited. The results of our study preferential involvement of episodic and working memory, executive functions, and attention and relatively less affectation of other cortical functions. In addition, anxiety and depression pictures are constant in our cohort. Several plasma chemokines concentrations were elevated compared with both, a non-SARS-Cov2 infected cohort of neurological outpatients or a control healthy general population. Severe Covid-19 patients can develop an amnesic and dysexecutive syndrome with neuropsychiatric manifestations. We do not know if the deficits detected can persist in the long term and if this can trigger or accelerate the onset of neurodegenerative diseases.

¿Reducen las estatinas el riesgo de glaucoma? revisión de las evidencias / Do statins reduce the risk of glaucoma? review of the evidences

Introducción: Los objetivos de este trabajo son revisar y resumir los datos publicados hasta el momento que relacionen el uso de estatinas con el riesgo de aparición o de agravamiento de glaucoma y plantear una hipótesis que explique los efectos protectores de las estatinas y su asociación con un menor riesgo de glaucoma. Método: se realizó una revisión en PubMed usando los términos “statins, hmg coa” o “hmg coa inhibitors” y “glaucoma” o “open angle glaucoma” o “intraocular pressure”. Se seleccionaron todos los artículos que incluían estudios clínicos o meta-análisis y se excluyeron comentarios, cartas a editor, artículos retractados e investigación en modelos animales. Todos los artículos fueron posteriores a 2004. Se emplearon en la revisión 17 artículos. Resultados: la mayor parte de los estudios muestran un efecto protector de las estatinas frente a la aparición y agravamiento del glaucoma de ángulo abierto. Sin embargo, otros estudios no llegan a encontrar una relación significativa e incluso alguno muestra una relación entre el glaucoma y el empleo de estatinas a altas dosis. Los efectos neuroprotectores y la inhibición de la Rho-quinasa podrían explicar los efectos encontrados. Conclusiones: la evidencia publicada no es suficiente como para recomendar el tratamiento con estatinas con el objetivo de prevenir el avance o la aparición del glaucoma. (AU)

Introduction: The objectives of this article are to review and summarize the updated published data that show the relation between treatment with statins and the incidence and progression of glaucoma. We also aimed to pose a hypothesis to explain the protective effects of statins and its association with glaucoma risk. Method: a review of the literature was carried out in the PubMed database considering the MeSH terms “statins, hmg coa” or “hmg coa inhibitors” and “glaucoma” or “open angle glaucoma” or “intraocular pressure”. All articles including clinical studies and meta-analysis were selected. Comments, letters to editors, retracted articles and research on animal models were excluded. All the articles were published from 2004. 17 articles were finally selected for review. Results: most of the studies showed a protective effect of statins on incidence or progression of open angle glaucoma. Nevertheless, other studies did not find a significant association and even one study found association between statin treatment at high doses and more incidence of glaucoma. Neuroprotective effects of statin and inhibition of Rho-kinase may help explain the described effects. Conclusions: The published results are not enough evidence to support statin recommendation as preventive treatment for the incidence or progression of glaucoma. (AU)

El reto del envejecimiento y la complejidad farmacoterapéutica en el paciente VIH + / The challenge of aging and pharmacoterapeutic complexity in the HIV + patient

Objetivo:Describir el conocimiento actual y el manejo del envejecimiento y la complejidad farmacoterapéutica en pacientes VIH +. Método: Se realizó una revisión bibliográfica, incluyéndose artículos, originales o revisiones, publicados en lengua inglesa o española, desde 2007 al 2017, que analizaron el envejecimiento y la complejidad farmacoterapéutica en pacientes VIH + . Se combinaron los términos: "Polypharmacy"/"Polifarmacia", "Aging"/"Envejecimiento", "Frailty"/"Fragilidad", "Complejidad Farmacoterapéutica"/"Medication Regimen Complexity" y "HIV"/"VIH". La revisión se realizó de forma independiente por dos autores. Se analizó el grado de concordancia según el índice Kappa. Resultados: Se analizaron 208 referencias bibliográficas, incluyéndose finalmente 68. Se ha identificado un envejecimiento de la población y un incremento de las comorbilidades asociadas, especialmente a partir de los 50 años. Se han descrito cambios inmunológicos similares a los que se generan en la población anciana no infectada. Esto condiciona, según estudios identificados, la prescripción del tratamiento antirretroviral. Paralelamente, el concepto de polifarmacia está cada vez más presente, definiéndose exclusivamente por el uso concomitante de cinco fármacos. La complejidad farmacoterapéutica, a través del Medication Regimen Complexity Index, se ha empezado a analizar y a relacionar con resultados en salud. Se ha evidenciado una necesidad de profundizar y aplicar conceptos ya conocidos en la población no VIH envejecida, como desprescripción, medicación potencialmente inapropiada, riesgo colinérgico, etc., aunque existen pocos resultados disponibles. Conclusiones: Existe un interés creciente en profundizar en la relación VIH y envejecimiento. La complejidad farmacoterapéutica está empezando a utilizarse como criterio de seguimiento farmacoterapéutico por su influencia en los resultados en salud. Es necesario manejar e incorporar nuevos conceptos que ayuden a la optimización farmacoterapéutica en esta población

Objective:To describe the current knowledge and management of aging and pharmacotherapeutic complexity in HIV + patients. Method: A review of literature was carried out, including articles, originals or reviews, published in English or Spanish, from 2007 to 2017, which analysed the aging and pharmacotherapeutic complexity in HIV + patients. The terms «Polypharmacy»/«Polifarmacia», «Aging»/«Envejecimiento», «Frailty»/«Fragilidad», «Complejidad Farmacoterapéutica»/«Medication Regimen Complexity» and «HIV»/«VIH» were combined. The review was carried out independently by two authors. The degree of agreement, according to the Kappa index, was analysed. Results: A total of 208 references were analysed, including, finally, only 68. An aging of the population and an increase in associated comorbidities have been identified, especially over 50 years-old. Immunological changes similar to those that are generated in a non-infected elderly population have been described. These conditions influencing the prescription of antiretroviral treatment, according to studies identified. In parallel, polypharmacy is increasingly present, being defined exclusively by the concomitant use of five drugs. Pharmacotherapeutic complexity, through the Medication Regimen Complexity Index, has begun to analyse and relate to health outcomes. There has been a need to know and apply concepts already known in non-HIV-aged population, such as deprescription, potentially inappropriate medication, cholinergic risk, although few results are available. Conclusions: There is a growing interest to know about the relationship between HIV and aging. Pharmacotherapeutic complexity is beginning to be used as a pharmacotherapeutic follow-up criterion due to its influence on health outcomes. It is necessary to manage and incorporate new concepts that help pharmacotherapeutic optimization in this population

The challenge of aging and pharmacoterapeutic complexity in the HIV + patient.

OBJECTIVE: To describe the current knowledge and management of aging and  pharmacotherapeutic complexity in HIV + patients. METHOD: A review of literature was carried out, including articles, originals or  reviews, published in English or Spanish, from 2007 to 2017, which analysed the aging and pharmacotherapeutic complexity in HIV + patients. The terms  «Polypharmacy¼/¼Polypharmacy¼, «Aging¼/¼Aging¼, «Frailty¼/¼Fragility¼,  «Pharmacotherapeutic Complexity¼/¼Medication Regimen Complexity¼ and  «HIV¼/"HIV¼ were combined. The review was carried out independently by two  authors. The degree of agreement, according to the Kappa index, was analysed. Results: A total of 208 references were analysed, including, finally, only 68. An  aging of the population and an increase in associated comorbidities have been  identified, especially over 50 years-old. Immunological changes similar to those  that are generated in a non-infected elderly population have been described.  These conditions influencing the prescription of antiretroviral treatment,  according to studies identified. In parallel, polypharmacy is increasingly present,  being defined exclusively by the concomitant use of five drugs.  Pharmacotherapeutic complexity, through the Medication Regimen Complexity  Index, has begun to analyse and relate to health outcomes. There has been a  need to know and apply concepts already known in non-HIV-aged population,  such as de-prescription, potentially inappropriate medication, cholinergic risk, although few results are available. CONCLUSIONS: There is a growing interest to know about the relationship between HIV and aging. Pharmacotherapeutic complexity is  beginning to be used as a pharmacotherapeutic follow-up criterion due to its influence on health outcomes. It is necessary to manage and incorporate new  concepts that help pharmacotherapeutic optimization in this population.

Objetivo: Describir el conocimiento actual y el manejo del envejecimiento y la  complejidad farmacoterapéutica en pacientes VIH ≥ .Método: Se realizó una revisión bibliográfica, incluyéndose artículos, originales o revisiones, publicados en lengua inglesa o española, desde 2007 al 2017, que analizaron el envejecimiento y la complejidad farmacoterapéutica  en pacientes VIH ≥ . Se combinaron los términos:  "Polypharmacy"/"Polifarmacia", "Aging"/"Envejecimiento", "Frailty"/"Fragilidad",  "Complejidad Farmacoterapéutica"/"Medication Regimen Complexity" y  "HIV"/"VIH". La revisión se realizó de forma independiente por dos autores. Se  analizó el grado de concordancia según el índice Kappa.Resultados: Se analizaron 208 referencias bibliográficas, incluyéndose finalmente 68. Se ha identificado un envejecimiento de la  población y un incremento de las comorbilidades asociadas, especialmente a  partir de los 50 años. Se han descrito cambios inmunológicos similares a los que  se generan en la población anciana no infectada. Esto condiciona, según estudios identificados, la prescripción del tratamiento antirretroviral. Paralelamente, el concepto de polifarmacia está cada vez más  presente, definiéndose exclusivamente por el uso concomitante de cinco  fármacos. La complejidad farmacoterapéutica, a través del Medication Regimen Complexity Index, se ha empezado a analizar y a relacionar con  resultados en salud. Se ha evidenciado una necesidad de profundizar y aplicar conceptos ya conocidos en la población no VIH envejecida, como  desprescripción, medicación potencialmente inapropiada, riesgo colinérgico, etc., aunque existen pocos resultados disponibles.Conclusiones: Existe un interés creciente en profundizar en la relación VIH y  envejecimiento. La complejidad farmacoterapéutica está empezando a utilizarse  como criterio de seguimiento farmacoterapéutico por su influencia en los  resultados en salud. Es necesario manejar e incorporar nuevos conceptos que  ayuden a la optimización farmacoterapéutica en esta población.

Ferulic acid, a bioactive component of rice bran, improves oxidative stress and mitochondrial biogenesis and dynamics in mice and in human mononuclear cells.

The aim of the study was to characterize the vascular effects of rice bran enzymatic extract (RBEE). ApoE-/- mice were fed a high-fat/cholesterol diet (HFD) or HFD supplemented with 5% RBEE for 21 weeks. RBEE prevented development of atherosclerotic plaques and oxidative stress in mouse aorta as well as the down-regulation of markers of mitochondrial biogenesis. Analysis of the bioactive components identified ferulic acid (FA) as responsible component. In healthy human volunteers, FA intake reduced NADPH oxidase activity, superoxide release, apoptosis and necrosis in peripheral blood mononuclear cells. Differentiation and proliferation of endothelial progenitor cells were improved. In summary, the study identifies FA as a major active component of rice bran, which improves expression of mitochondrial biogenesis and dynamics markers and reduces oxidative stress in a mouse model of vascular damage as well as in endothelial cells and human mononuclear cells.

Rice bran enzymatic extract reduces atherosclerotic plaque development and steatosis in high-fat fed ApoE-/- mice.

OBJECTIVE: Rice bran is a by-product of rice milling and is rich in bioactive molecules such as γ-oryzanol, phytosterols, and tocotrienols. The rice bran enzymatic extract (RBEE) previously showed vessel remodeling prevention and lipid-lowering, antioxidant, anti-inflammatory, and antiapoptotic activities. The aim of this study was to identify RBEE hypolipidemic mechanisms and to study the effects of RBEE on the progression of atherosclerosis disease and linked vascular dysfunction and liver steatosis in apolipoprotein E-knockout (ApoE-/-) mice fed low- or high-fat (LFD, HFD, respectively) and cholesterol diets. METHODS: ApoE-/- mice were fed LFD (13% kcal) or HFD (42% kcal) supplemented or not supplemented with 1 or 5% RBEE (w/w) for 23 wk. Then, serum, aorta, liver, and feces were collected and flash frozen for further analysis. RESULTS: RBEE supplementation of HFD improved serum values by augmenting high-density lipoprotein cholesterol and preventing total cholesterol and aspartate aminotransferase increase. 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase activity was attenuated (1 and 5% RBEE) and cholesterol excretion increased (5% RBEE). Diet supplementation with 5% RBEE reduced plaque development regardless of the diet. In HFD-fed mice, both doses of RBEE reduced lipid deposition and macrophage infiltration in the aortic sinus and downregulated intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 expression. None of these effects was observed in mice fed LFD. Liver steatosis was reduced by RBEE supplementation of LFD (1% RBEE) and HFD (1 and 5% RBEE) and nuclear peroxisome proliferator-activated receptor-α expression upregulated in the HDF 5% RBEE group. CONCLUSION: Regular consumption of RBEE-supplemented HFD reduced plaque development and liver steatosis by decreasing inflammation and hyperlipidemia through an HMG-CoA reductase activity and lipid excretion-related mechanism.

Development of a taxonomy for pharmaceutical interventions in HIV+ patients based on the CMO model / Desarrollo de una taxonomía de las intervenciones farmacéuticas en pacientes VIH+ basados en el modelo CMO

Objective: To agree on a proposal for pharmaceutical interventions and establish their classification taxonomy according to the CMO-Pharmaceutical Care Model (Capacity-Motivation-Opportunity). Method: A study conducted between March and May, 2016. Two phases of development were defined. A literature review was initially conducted. Then, the DELPHI-Rand-UCLA methodology was used in order to reach a consensus about those interventions selected, and to define the taxonomy. Fifteen (15) experts, specialists in Pharmaceutical Care for HIV+ patients, were selected. This selection was explicitly conducted, following a protocol in order to avoid any bias. An initial proposal was developed according to the interventions extracted from Phase 1. These were tentatively classified according to the CMO Model, in a category based on their design and utility. Three issues were raised from the initial question: Do you agree with the proposed classification? If not, there was an option to re-categorize. Additionally, they were asked about the importance, priority and impact to achieve pharmacotherapeutic objectives that they would assign to it. Interventions were classified according to the degree of agreement. Once a consensus was reached, the final taxonomy was established. Results: Eighteen (18) articles were finally considered. The initial proposal included 20 pharmaceutical interventions with the following classification: seven in Capacity, eight in Motivation, and five in Opportunity. Those interventions considered to have greater importance and priority were: Review and Validation, Safety, and Adherence. The interventions with the greatest impact were: Review and Validation, Coordination, Adherence, and Motivation. On the other hand, the lowest scores for importance were for: Planning and Social Coordination; and in terms of impact: Social Coordination. Conclusions: The taxonomy reached by consensus will allow to classify pharmaceutical interventions with the new model, and therefore to conduct an improved research and patient car (AU)

Objetivo: Consensuar una propuesta de intervenciones farmacéuticas y llevar a cabo su taxonomía de clasificación según el modelo de Atención Farmacéutica-CMO (Capacidad-Motivación-Oportunidad). Método: Estudio realizado entre marzo-mayo de 2016. Se definieron dos fases de desarrollo. Inicialmente, se realizó una revisión bibliográfica. A continuación, para consensuar las intervenciones seleccionadas y definir la taxonomía se utilizó metodología DELPHI-Rand-UCLA. Se seleccionaron 15 expertos, especialistas en Atención Farmacéutica al paciente VIH+. La selección se realizó explícitamente, siguiendo un protocolo para evitar sesgos. Se elaboró, inicialmente, una propuesta a partir de las intervenciones extraídas de la fase-1. Se clasificaron tentativamente según el Modelo-CMO en una categoría según su diseño y utilidad. Se plantearon tres preguntas a partir de la cuestión inicial: ¿Está de acuerdo con la clasificación propuesta? En caso negativo, se daba opción de recategorizar. Adicionalmente, se planteó qué importancia, prioridad e impacto en la consecución de objetivos farmacoterapéuticos le daría. Las intervenciones se clasificaron en función del grado de acuerdo. Una vez consensuadas, se realizó la taxonomía definitiva. Resultados: Se consideraron finalmente 18 artículos. La propuesta inicial incluyó 20 intervenciones farmacéuticas clasificadas siete en Capacidad, ocho en Motivación y cinco en Oportunidad. Las intervenciones consideradas de mayor importancia y prioridad fueron: revisión y validación, seguridad y adherencia. Las de mayor impacto fueron: revisión y validación, coordinación, adherencia y motivación. Por contra, las de menor puntuación en importancia fueron: planificación y coordinación social y, en impacto, coordinación social. Conclusiones: La taxonomía consensuada permitirá clasificar las intervenciones farmacéuticas realizadas con el nuevo modelo y, así, profundizar en la investigación y la mejora asistencial (AU)

Development of a taxonomy for pharmaceutical interventions in HIV+ patients based on the CMO model.

OBJECTIVE: To agree on a proposal for pharmaceutical interventions and establish their classification taxonomy according to the CMO-Pharmaceutical Care Model (Capacity-Motivation- Opportunity). METHOD: A study conducted between March and May, 2016. Two phases of development were defined. A literature review was initially conducted. Then, the DELPHI-Rand-UCLA methodology was used in order to reach a consensus about those interventions selected, and to define the taxonomy. Fifteen (15) experts, specialists in Pharmaceutical Care for HIV+ patients, were selected. This selection was explicitly conducted, following a protocol in order to avoid any bias. An initial proposal was developed according to the interventions extracted from Phase 1. These were tentatively classified according to the CMO Model, in a category based on their design and utility. Three issues were raised from the initial question: Do you agree with the proposed classification? If not, there was an option to re-categorize. Additionally, they were asked about the importance, priority and impact to achieve pharmacotherapeutic objectives that they would assign to it. Interventions were classified according to the degree of agreement. Once a consensus was reached, the final taxonomy was established. RESULTS: Eighteen (18) articles were finally considered. The initial proposal included 20 pharmaceutical interventions with the following classification: seven in Capacity, eight in Motivation, and five in Opportunity. Those interventions considered to have greater importance and priority were: Review and Validation, Safety, and Adherence. The interventions with the greatest impact were: Review and Validation, Coordination, Adherence, and Motivation. On the other hand, the lowest scores for importance were for: Planning and Social Coordination; and in terms of impact: Social Coordination. CONCLUSIONS: The taxonomy reached by consensus will allow to classify pharmaceutical interventions with the new model, and therefore to conduct an improved research and patient care.

Objetivo: Consensuar una propuesta de intervenciones farmacéuticas y llevar a cabo su taxonomía de clasificación según el modelo de Atención Farmacéutica-CMO (Capacidad-Motivación- Oportunidad). Método: Estudio realizado entre marzo-mayo de 2016. Se definieron dos fases de desarrollo. Inicialmente, se realizó una revisión bibliográfica. A continuación, para consensuar las intervenciones seleccionadas y definir la taxonomía se utilizó metodología DELPHI-Rand-UCLA. Se seleccionaron 15 expertos, especialistas en Atención Farmacéutica al paciente VIH+. La selección se realizó explícitamente, siguiendo un protocolo para evitar sesgos. Se elaboró, inicialmente, una propuesta a partir de las intervenciones extraídas de la fase-1. Se clasificaron tentativamente según el Modelo-CMO en una categoría según su diseño y utilidad. Se plantearon tres preguntas a partir de la cuestión inicial: ¿Está de acuerdo con la clasificación propuesta? En caso negativo, se daba opción de recategorizar. Adicionalmente, se planteó qué importancia, prioridad e impacto en la consecución de objetivos farmacoterapéuticos le daría. Las intervenciones se clasificaron en función del grado de acuerdo. Una vez consensuadas, se realizó la taxonomía definitiva. Resultados: Se consideraron finalmente 18 artículos. La propuesta inicial incluyó 20 intervenciones farmacéuticas clasificadas siete en Capacidad, ocho en Motivación y cinco en Oportunidad. Las intervenciones consideradas de mayor importancia y prioridad fueron: revisión y validación, seguridad y adherencia. Las de mayor impacto fueron: revisión y validación, coordinación, adherencia y motivación. Por contra, las de menor puntuación en importancia fueron: planificación y coordinación social y, en impacto, coordinación social. Conclusiones: La taxonomía consensuada permitirá clasificar las intervenciones farmacéuticas realizadas con el nuevo modelo y, así, profundizar en la investigación y la mejora asistencial.

Diet supplementation with rice bran enzymatic extract restores endothelial impairment and wall remodelling of ApoE(-/-) mice microvessels.

BACKGROUND AND AIMS: Small mesenteric artery resistance and functionality are key factors for the maintenance of blood homeostasis. We attained to evaluate the effects of a rice bran enzymatic extract (RBEE) on structural, mechanic and myogenic alterations and endothelial dysfunction secondary to atherosclerosis disease. METHODS: Seven week-old ApoE(-/-) mice were fed on standard (ST) or high fat (HF) diets supplemented or not with 1 or 5% RBEE (w/w) for 23 weeks. Wild-type C57BL/6J mice fed on ST diet served as controls. Small mesenteric arteries were mounted in a pressure myograph in order to evaluate structural, mechanical and myogenic properties. Vascular reactivity was assessed in the presence of different combinations of inhibitors: l-NAME, indometacin, apamin and charybdotoxin. RESULTS: ApoE(-/-) mice fed on ST and HF diets showed different structural and mechanical alterations, alleviated by RBEE supplementation of ST and HF diets. C57BL/6J was characterized by increased expression of IKCa (199.3%, p = 0.023) and SKCa (133.2%, p = 0.026), resulting in higher EDHF participation (p = 0.0001). However, NO release was more relevant to ApoE(-/-) mice vasodilatation. HF diet reduced the amount of NO released due to 2-fold increase of eNOS phosphorylation in the inhibitory residue Thr495 (p = 0.034), which was fully counteracted by RBEE supplementation (p = 0.028), restoring ACh-induced vasodilatation (p = 0.00006). Dihydroethidium fluorescence of superoxide and picrosirius red staining of collagen were reduced by RBEE supplementation of HF diet by 76.91% (p = 0.022) and 65.87% (p = 0.030), respectively. CONCLUSION: RBEE supplemented diet reduced vessel remodeling and oxidative stress. Moreover, RBEE supplemented diet increased NO release by downregulating p-eNOS(Thr495), thus, protecting the endothelial function.

Structural, mechanical and myogenic properties of small mesenteric arteries from ApoE KO mice: characterization and effects of virgin olive oil diets.

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.

Water-soluble rice bran enzymatic extract attenuates dyslipidemia, hypertension and insulin resistance in obese Zucker rats.

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.

Endothelium-dependent vasodilator and antioxidant properties of a novel enzymatic extract of grape pomace from wine industrial waste.

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.

Propionyl-L-carnitine corrects metabolic and cardiovascular alterations in diet-induced obese mice and improves liver respiratory chain activity.

AIMS: Obesity is a primary contributor to acquired insulin resistance leading to the development of type 2 diabetes and cardiovascular alterations. The carnitine derivate, propionyl-L-carnitine (PLC), plays a key role in energy control. Our aim was to evaluate metabolic and cardiovascular effects of PLC in diet-induced obese mice. METHODS: C57BL/6 mice were fed a high-fat diet for 9 weeks and then divided into two groups, receiving either free- (vehicle-HF) or PLC-supplemented water (200 mg/kg/day) during 4 additional weeks. Standard diet-fed animals were used as lean controls (vehicle-ST). Body weight and food intake were monitored. Glucose and insulin tolerance tests were assessed, as well as the HOMA(IR), the serum lipid profile, the hepatic and muscular mitochondrial activity and the tissue nitric oxide (NO) liberation. Systolic blood pressure, cardiac and endothelial functions were also evaluated. RESULTS: Vehicle-HF displayed a greater increase of body weight compared to vehicle-ST that was completely reversed by PLC treatment without affecting food intake. PLC improved the insulin-resistant state and reversed the increased total cholesterol but not the increase in free fatty acid, triglyceride and HDL/LDL ratio induced by high-fat diet. Vehicle-HF exhibited a reduced cardiac output/body weight ratio, endothelial dysfunction and tissue decrease of NO production, all of them being improved by PLC treatment. Finally, the decrease of hepatic mitochondrial activity by high-fat diet was reversed by PLC. CONCLUSIONS: Oral administration of PLC improves the insulin-resistant state developed by obese animals and decreases the cardiovascular risk associated to this metabolic alteration probably via correction of mitochondrial function.

Vascular contribution of adrenomedullin to microcirculatory improvement in experimental colitis.

The effect of adrenomedullin (AM), a peptide that has demonstrated vasodilatory activity, was studied in the colon and small mesenteric arteries of rats in a chronic model of inflammatory bowel disease. AM (50 ng/kg/day) was administered i.p. daily, starting 24h after trinitrobenzensulfonic acid (TNBS, 30 mg) instillation. After 14 days, rats were sacrificed, colons were macroscopically analyzed and biochemical parameters (myeloperoxidase activity, cytokines, cyclooxygenase-2 (COX-2) as well as inducible nitric oxide synthase (iNOS) expression) were determined. Vascular function of small mesenteric arteries was assessed by addition of phenylephrine (10⁻8 to 10⁻4 mol/L) and participation of COX and NOS pathways was also evaluated by using different inhibitors: indomethacin, NS-398, L-NNA, and 1400 w. Chronic AM treatment significantly reduced colonic macroscopic damage and inflammation markers. TNBS instillation induced COX-2 and iNOS expressions in colon and small mesenteric arteries; AM treatment decreased COX-2 expression only in microvessels from rats with colitis. An attenuation of phenylephrine-induced contraction was detected in small mesenteric arteries from both TNBS and AM-treated rats. COX and NOS inhibitors altered the contractile ability of phenylephrine in small mesenteric arteries from TNBS rats, suggesting the involvement of COX-2 and iNOS derived factors in the deleterious effect of TNBS on vascular reactivity; AM administration was able to reduce such alteration. Finally, treatment with the peptide significantly reduced colonic nitric oxide (NO) levels, without affecting plasma concentration. In conclusion, AM showed beneficial effects in the restoration of vascular function through the regulation of vasoactive products derived from COX-2 and iNOS.

Critical update for the clinical use of L-carnitine analogs in cardiometabolic disorders.

Acetyl-L-carnitine (ALC) and propionyl-L-carnitine (PLC) are two naturally occurring carnitine derivates formed by carnitine acetyltransferase. The beneficial cardiovascular effects of ALC and PLC have been extensively evaluated in animals and humans during the last 20 years. For instance, many clinical trials have suggested ALC and PLC as potential strategies in the management of peripheral arterial disease, heart and cerebral ischemia, and congestive heart failure. As a result, several experts have already aimed to revise the clinical evidence supporting the therapeutic use of ALC and PLC. On the basis of their conclusions, our aim was a critical review of the effectiveness of ALC and PLC in the treatment of cardiovascular diseases. Type 2 diabetes mellitus is an independent risk factor for the development of cardiovascular disease. Therefore we also describe recent studies that have addressed the emerging use of ALC and PLC amelioration of the insulin resistant state and its related morbidities.

Endothelial dysfunction and aging: an update.

Aging is an important risk factor for the development of many cardiovascular diseases as atherosclerosis and hypertension with a common underlying circumstance: the progressive decline of endothelial function. Vascular endothelial dysfunction occurs during the human aging process and is accompanied by deterioration in the balance between vasodilator and vasoconstriction substances produced by the endothelium. This imbalance is mainly characterized by a progressive reduction of the bioavailability of nitric oxide (NO) and an increase in the production of cyclooxygenase (COX)-derived vasoconstrictor factors. Both circumstances are in turn related to an increased production of reactive oxygen and nitrogen species. The aim of this review is to describe the pathophysiological mechanisms involved in the endothelial function declination that accompanies the multifactorial aging process, including alterations related to oxidative stress and pro-inflammatory cytokines, senescence of endothelial cells and genetic factors.

Effects of chronic treatment with the CB1 antagonist, rimonabant on the blood pressure, and vascular reactivity of obese Zucker rats.

Rimonabant (RM) is a cannabinoid CB1 receptor antagonist useful in the treatment of obesity associated cardiovascular risk factors. Since cannabinoids are vasoactive compounds, the aim of this study is to evaluate the effect of chronic treatment with RM on systolic blood pressure (SBP), and endothelial and vascular reactivity. Obese Zucker rats (OZRs) and their lean counterparts were orally treated during 20 weeks with either RM (10 mg/kg/day). Endothelial and vascular function was assessed in aorta and small mesenteric arteries (SMAs) by concentration response curves to acetylcholine (ACh) and phenylephrine (Phe), respectively. Participation of nitric oxide (NO) was evaluated by incubation with the NO synthase (NOS) inhibitor N(G)-nitro-l-arginine methyl ester (L-NAME) and cyclooxygenase (COX)-derived products involvement was analyzed by incubation with indomethacin (INDO). Plasma lipid profile, insulin and adiponectin were also analyzed. Sympathetic activity was evaluated by urinary excretion of noradrenaline. As expected, RM decreased body weight gain and enhanced adiponectin concentration. Insulin resistance and sympathetic activity were also decreased. The increase in SBP observed in OZRs was reduced by treatment with RM. Aortae and SMAs from OZRs exhibited lower contractile response to Phe, being this effect prevented by RM administration. Although ACh-induced response and NO participation remained unaltered with obesity, enhanced COX-derived constrictor products were found in OZRs. RM treatment neither altered endothelium-dependent relaxation nor L-NAME-sensitive component of the response. Nevertheless, it was able to regulate COX-derived vasoactive products participation. Those effects may contribute to explain some of the cardiovascular protective actions elicited by this drug.