Extra Virgin Oil Polyphenols Improve the Protective Effects of Hydroxytyrosol in an In Vitro Model of Hypoxia-Reoxygenation of Rat Brain

Hydroxytyrosol (HT) is the component primarily responsible for the neuroprotective effect of extra virgin olive oil (EVOO). However, it is less effective on its own than the demonstrated neuroprotective effect of EVOO, and for this reason, it can be postulated that there is an interaction between several of the polyphenols of EVOO. The objective of the study was to assess the possible interaction of four EVOO polyphenols (HT, tyrosol, dihydroxyphenylglycol, and oleocanthal) in an experimental model of hypoxia-reoxygenation in rat brain slices. The lactate dehydrogenase (LDH) efflux, lipid peroxidation, and peroxynitrite production were determined as measures of cell death, oxidative stress, and nitrosative stress, respectively. First, the polyphenols were incubated with the brain slices in the same proportions that exist in EVOO, comparing their effects with those of HT. In all cases, the cytoprotective and antioxidant effects of the combination were greater than those of HT alone. Second, we calculated the concentration–effect curves for HT in the absence or presence of each polyphenol. Tyrosol did not significantly modify any of the variables inhibited by HT. Dihydroxyphenylglycol only increased the cytoprotective effect of HT at 10 μM, while it increased its antioxidant effect at 50 and 100 μM and its inhibitory effect on peroxynitrite formation at all the concentrations tested. Oleocanthal increased the cytoprotective and antioxidant effects of HT but did not modify its inhibitory effect on nitrosative stress. The results of this study show that the EVOO polyphenols DHPG and OLC increase the cytoprotective effect of HT in an experimental model of hypoxia-reoxygenation in rat brain slices, mainly due to a possibly synergistic effect on HT’s antioxidant action. These results could explain the greater neuroprotective effect of EVOO than of the polyphenols alone

The Effect of the Extra Virgin Olive Oil Minor Phenolic Compound 3′,4′-Dihydroxyphenylglycol in Experimental Diabetic Kidney Disease

The aim of this study was to analyze the possible nephroprotective effect of 3’,4’-dihydroxyphenylglycol (DHPG), a polyphenolic compound of extra virgin olive oil (EVOO), on renal lesions in an experimental model of type 1 diabetes. Rats were distributed as follows: healthy normoglycemic rats (NDR), diabetic rats treated with saline (DR), and DR treated with 0.5 mg/kg/day or 1 mg/kg/day of DHPG. DR showed a significantly higher serum and renal oxidative and nitrosative stress profile than NDR, as well as reduced prostacyclin production and renal damage (defined as urinary protein excretion, reduced creatinine clearance, increased glomerular volume, and increased glomerulosclerosis index). DHPG reduced the oxidative and nitrosative stress and increased prostacyclin production (a 59.2% reduction in DR and 34.7–7.8% reduction in DHPG-treated rats), as well as 38–56% reduction in urinary protein excretion and 22–46% reduction in glomerular morphological parameters (after the treatment with 0.5 or 1 mg/kg/day, respectively). Conclusions: DHPG administration to type 1-like diabetic rats exerts a nephroprotective effect probably due to the sum of its antioxidant (Pearson’s coefficient 0.68–0.74), antinitrosative (Pearson’s coefficient 0.83), and prostacyclin production regulator (Pearson’s coefficient 0.75) effects.This study was supported, in part, by the Consejería de Salud. Junta de Andalucía (Spain), Proyectos de Investigación en Salud [Regional Ministry of Health. Junta de Andalucía (Spain), Health Research Projects] (PI-0129-2017). Partial funding for open access charge: Universidad de Málag

Sinergismo entre 3,4-dihidroxifenilglicol e hidroxitirosol sobre biomarcadores cardiovasculares, estrés oxidativo y nitrosativo en un modelo experimental de Diabetes Mellitus tipo 1.

Resumen Póster: Objetivo El objetivo de este estudio fue evaluar el efecto sinérgico de dos polifenoles del aceite de oliva virgen extra, 3,4,-dihidroxifenilglicol (DHPG) e hidroxitirosol (HT), sobre biomarcadores cardiovasculares en un modelo experimental de Diabetes Mellitus tipo 1. Material y Métodos Se estudiaron siete grupos de animales: (1) ratas no diabéticas (NDR), (2) ratas diabéticas (DR), (3) DR tratadas con HT (5 mg/kg/día), (4) DR tratadas con DHPG (0,5 mg/kg/día), (5) DR tratadas con DPHG (1 mg/kg/día), (6) DR tratadas con HT + DHPG (0,5 mg/kg/día), y (7) DR tratadas con HT + DHPG (1 mg/kg/día). Se analizaron algunos biomarcadores cardiovasculares (agregación plaquetaria, tromboxano B2, prostaciclina, mieloperoxidasa y VCAM-1, variables de estrés oxidativo (peroxidación lipídica, glutatión, actividad antioxidante total, 8-isoprostanos, 8-hidroxi-2-deoxiguanosina y LDL oxidada), y estrés nitrosativo (3-nitrotirosina). Resultados Los animales diabéticos mostraron un desequilibrio en todas las variables analizadas. HT ejerció un efecto regulador a la baja sobre los biomarcadores protrombóticos y antioxidantes, al tiempo que frenó el descenso de prostaciclina. DHPG presentó un perfil similar, pero cuantitativamente inferior. HT y DHPG mostraron un efecto sinérgico en la reducción de la agregación plaquetaria, la producción de prostaciclina, mieloperoxidasa, VCAM-1 y del estrés oxidativo y nitrosativo. Conclusiones Se demuestra sinergismo entre 3,4-dihidroxifenilglicol e hidroxitirosol. Este sinergismo podría ser importante para el desarrollo de aceites funcionales, enriquecidos con estos dos polifenoles en la proporción utilizada en este estudio, para la prevención de la enfermedad cardiovascular.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Efecto de 3,4-dihidroxifenilglicol, polifenol del aceite de oliva virgen extra, en la nefropatía diabética experimental.

Objetivo: El objetivo de este estudio fue analizar el efecto nefroprotector de 3',4'-dihidroxifenilglicol (DHPG), un compuesto polifenólico del aceite de oliva virgen extra (AOVE), sobre las lesiones renales en un modelo experimental de diabetes tipo 1. Material y Métodos: Estudio ex vivo mediante modelo experimental de Diabetes Mellitus tipo 1 en ratas Wistar. Grupos: ratas normoglucémicas (NDR), ratas diabéticas (DR) tratadas con solución salina, y DR tratadas con DHPG (0,5 mg/kg/día o 1 mg/kg/día). Valoración del estrés oxidativo: determinación de malondialdehído (MDA), capacidad antioxidante total, glutatión, 3-nitrotirosina, 8-isoprostano, 8-hidroxi-2-deoxiguanosina, 11-dehidrotromboxano B2 y 6-keto-prostaglandina F1, en suero, orina y tejido renal. Determinación del perfil renal (aclaramiento de creatinina) y las concentraciones de glucosa. Análisis morfométrico de secciones de riñón teñidas con hematoxilina-eosina y ácido peryódico de Schiff (PAS): volumen glomerular y glomeruloesclerosis. Resultados: Las DR mostraron un perfil de estrés oxidativo y nitrosativo sérico y renal significativamente mayor que las NDR, así como una menor producción de prostaciclina y un daño renal evidente (definido como excreción urinaria de proteínas, menor aclaramiento de creatinina, mayor volumen glomerular y mayor índice de glomeruloesclerosis). DHPG redujo el estrés oxidativo, nitrosativo (una reducción del 59,2% y del 34,7%, respectivamente, respecto a las DR no tratadas) y aumentó la producción de prostaciclina (7,8% en las ratas tratadas con DHPG). Así como, una reducción del 38-56% en la excreción urinaria de proteínas y del 22-46% en los parámetros morfológicos glomerulares (tras el tratamiento con 0,5 o 1 mg/kg/día, respectivamente).Conclusiones: La administración de DHPG a ratas diabéticas tipo 1 ejerce un efecto nefroprotector, probablemente debido a la suma de sus propiedades antioxidantes, antinitrosativas y regulador de la producción de prostaciclina.Universidad de Málaga. Campus de Excelencia

Neuroprotective Effect of 3′,4′-Dihydroxyphenylglycol in Type-1-like Diabetic Rats—Influence of the Hydroxytyrosol/3′,4′-dihydroxyphenylglycol Ratio

The aim of this study was to assess the possible neuroprotective effect of 3′,4′-dihydroxyphenylglycol (DHPG), a polyphenol from extra virgin olive oil (EVOO), in an experimental model of diabetes and whether this effect is modified by the presence of another EVOO polyphenol, hydroxytyrosol (HT). The neuroprotective effect was assessed in a hypoxia–reoxygenation model in brain slices and by quantifying retinal nerve cells. The animals were distributed as follows: (1) normoglycemic rats (NDR), (2) diabetic rats (DR), (3) DR treated with HT (5 mg/kg/day p.o.), (4) DR treated with DHPG (0.5 mg/kg/day), or (5) with 1 mg/kg/day, (6) DR treated with HT plus DHPG 0.5 mg/kg/day, or (7) HT plus 1 mg/kg/day p.o. DHPG. Diabetic animals presented higher levels of oxidative stress variables and lower numbers of neuronal cells in retinal tissue. The administration of DHPG or HT reduced most of the oxidative stress variables and brain lactate dehydrogenase efflux (LDH) as an indirect index of cellular death and also reduced the loss of retinal cells. The association of DHPG+HT in the same proportions, as found in EVOO, improved the neuroprotective and antioxidant effects of both polyphenols.This study was supported, in part, by the Consejería de Salud. Junta de Andalucía (Spain), Proyectos de Investigación en Salud [Regional Ministry of Health. Junta de Andalucía (Spain), Health Research Projects] (PI-0129-2017). Partial funding for open access charge: Universidad de Málaga

Effectiveness of an intervention for improving drug prescription in primary care patients with multimorbidity and polypharmacy:Study protocol of a cluster randomized clinical trial (Multi-PAP project)

This study was funded by the Fondo de Investigaciones Sanitarias ISCIII (Grant Numbers PI15/00276, PI15/00572, PI15/00996), REDISSEC (Project Numbers RD12/0001/0012, RD16/0001/0005), and the European Regional Development Fund ("A way to build Europe").Background: Multimorbidity is associated with negative effects both on people's health and on healthcare systems. A key problem linked to multimorbidity is polypharmacy, which in turn is associated with increased risk of partly preventable adverse effects, including mortality. The Ariadne principles describe a model of care based on a thorough assessment of diseases, treatments (and potential interactions), clinical status, context and preferences of patients with multimorbidity, with the aim of prioritizing and sharing realistic treatment goals that guide an individualized management. The aim of this study is to evaluate the effectiveness of a complex intervention that implements the Ariadne principles in a population of young-old patients with multimorbidity and polypharmacy. The intervention seeks to improve the appropriateness of prescribing in primary care (PC), as measured by the medication appropriateness index (MAI) score at 6 and 12months, as compared with usual care. Methods/Design: Design:pragmatic cluster randomized clinical trial. Unit of randomization: family physician (FP). Unit of analysis: patient. Scope: PC health centres in three autonomous communities: Aragon, Madrid, and Andalusia (Spain). Population: patients aged 65-74years with multimorbidity (≥3 chronic diseases) and polypharmacy (≥5 drugs prescribed in ≥3months). Sample size: n=400 (200 per study arm). Intervention: complex intervention based on the implementation of the Ariadne principles with two components: (1) FP training and (2) FP-patient interview. Outcomes: MAI score, health services use, quality of life (Euroqol 5D-5L), pharmacotherapy and adherence to treatment (Morisky-Green, Haynes-Sackett), and clinical and socio-demographic variables. Statistical analysis: primary outcome is the difference in MAI score between T0 and T1 and corresponding 95% confidence interval. Adjustment for confounding factors will be performed by multilevel analysis. All analyses will be carried out in accordance with the intention-to-treat principle. Discussion: It is essential to provide evidence concerning interventions on PC patients with polypharmacy and multimorbidity, conducted in the context of routine clinical practice, and involving young-old patients with significant potential for preventing negative health outcomes. Trial registration: Clinicaltrials.gov, NCT02866799Publisher PDFPeer reviewe

Adherencia al tratamiento en pacientes polimedicados mayores de 65 años con prescripción por principio activo

Objetivo: Valorar el nivel de adherencia al tratamiento y los factores relacionados en polimedicados mayores de 65 con prescripción por principio activo. Diseño: Estudio observacional, descriptivo, transversal, sobre polimedicados mayores de 65 años adscritos a los centros de atención primaria del Distrito Sanitario Costa del Sol y del Área Sanitaria Norte de Málaga. Se ha realizado entre enero del 2011 y septiembre del 2012, sobre una población de 375 individuos obtenida mediante muestreo aleatorio simple a partir de las listas de pacientes proporcionadas por cada centro. Los datos se recogieron mediante entrevista, sobre hoja estructurada de recogida de datos y previa firma del consentimiento informado. Variables del estudio: Variable principal de resultado: adherencia al tratamiento (test de Morisky-Green). Variables predictoras: Prescripción por principio activo, variables sociodemográficas, clínicas y relacionadas con la medicación. Se efectuó un análisis descriptivo de las variables. La inferencia estadística se realizó mediante análisis bivariante (test de la t de Student o U de Mann Whitney y chi al cuadrado), controlándose los factores de confusión mediante análisis multivariante (regresión lineal y logística). Resultados: El cumplimiento terapéutico se sitúa en el 51,7%, no apreciándose diferencias estadísticamente significativas con respecto al sexo o la edad. Encontramos relación con residir en zona de interior (p = 0,001), vivir acompañados (p < 0,05) y no presentar riesgo de ansiedad (p = 0,046). Conclusiones: La adherencia es similar a los estudios realizados, independientemente de si la prescripción es por principio activo. El incumplimiento fue mayor en individuos que viven solos, en población costera y con riesgo de ansiedad

Medication-related factors associated with health-related quality of life in patients older than 65 years with polypharmacy

<div><p>In the current public health framework, the importance of medication as a determinant of citizens’ health has emerged as a factor warranting special attention. Most studies investigating the relationship between medication and quality of life do so from the perspective of adherence. However, other medication-related factors identified at home visits may be associated with health-related quality of life.</p><p>Methods and design</p><p>Objective: To describe the relationship between medication-related factors and the health-related quality of life in patients older than 65 years who use multiple medications (polypharmacy).</p><p>Design: Cross-sectional descriptive study.</p><p>Setting: Primary care.</p><p>Participants: Patients older than 65 years who use multiple medications (n = 375).</p><p>Measurements: The main outcome measure was health-related quality of life according to the EuroQol-5D instrument. Sociodemographic, clinical and medication-related variables were recorded during home interviews.</p><p>Results</p><p>Mean age was 74.72 ± 5.59 years, and 65.5% of our participants were women. The global level of health-related quality of life according to the EQ-5D visual analog scale was 59.25 ± 20.92. Of the five EuroQol dimensions, anxiety/depression and pain were the most frequently reported, while mobility and self-care were the dimensions with the greatest impact on self-reported quality of life. Multivariate analysis indicated that functional independence was the factor most strongly associated (β = 14.27 p < 0.001) with better health-related quality of life, while illiteracy (β = −13.58 p < 0.001), depression (β = −10.13 p < 0.001), social risk (β = −7.23 p = 0.004) and using more than 10 medicines (β = −4.85 p = 0.009) were strongly associated with a poorer health-related quality of life.</p><p>Conclusions</p><p>Factors inherent within the patient such as functional incapacity, cognitive impairment and social and emotional problems were the main constraints to quality of life in our study population. The number of medicines taken was negatively related with quality of life.</p></div

Mean EuroQol-5D results by age and sex.

<p>Mean EuroQol-5D results by age and sex.</p

Results on the EQ-Index (0–1) and EQ-VAS (0–100) according to the study variable.

<p>Results on the EQ-Index (0–1) and EQ-VAS (0–100) according to the study variable.</p