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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). Design: Cross-sectional descriptive study. Setting: Primary care. Participants: Patients older than 65 years who use multiple medications (n = 375). 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. 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. 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.

The objective of this study was to assess a possible synergistic effect of two extra-virgin olive oil polyphenols, 3,4,-dyhydroxyphenylglycol (DHPG) and hydroxytyrosol (HT), in an experimental model of type 1 diabetes. Seven groups of animals were studied: (1) Nondiabetic rats (NDR), (2) 2-month-old diabetic rats (DR), (3) DR treated with 5 mg/kg/day p.o. HT, (4) DR treated with 0.5 mg/kg/day p.o. DHPG, (5) DR treated with 1 mg/kg/day p.o. DHPG, (6) DR treated with HT + DHPG (0.5), (7) DR treated with HT + DHPG (1). Oxidative stress variables (lipid peroxidation, glutathione, total antioxidant activity, 8-isoprostanes, 8-hydroxy-2-deoxyguanosine, and oxidized LDL), nitrosative stress (3-nitrotyrosine), and some cardiovascular biomarkers (platelet aggregation, thromboxane B2, prostacyclin, myeloperoxidase, and vascular cell adhesion protein 1 (VCAM-1)) were analyzed. The diabetic animals showed an imbalance in all of the analyzed variables. HT exerted an antioxidant and downregulatory effect on prothrombotic biomarkers while reducing the fall of prostacyclin. DHPG presented a similar, but quantitatively lower, profile. HT plus DHPG showed a synergistic effect in the reduction of oxidative and nitrosative stress, platelet aggregation, production of prostacyclin, myeloperoxidase, and VCAM-1. This synergism could be important for the development of functional oils enriched in these two polyphenols in the proportion used in this study.

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.

Hydroxytyrosol acetate (HT-AC) is a polyphenol present in virgin olive oil (VOO) at a proportion similar to hydroxytyrosol (HT) (160–479 μmol/kg oil). The present study was designed to measure the in vitro platelet antiaggregating activity of HT-AC in human whole blood, and compare this effect with that of HT and acetylsalicylic acid (ASA). The experiments were designed according to the standard procedure to investigate the activity of ASA. HT-AC and HT inhibited platelet aggregation induced by ADP, collagen or arachidonic acid in both whole blood and platelet-rich plasma (PRP). ASA and HT-AC had a greater effect in whole blood than in PRP when ADP or collagen was used as inducer. ASA and HT-AC had a greater effect in PRP+leucocytes than in PRP alone. All three compounds inhibited platelet thromboxane B2 and leucocyte 6-keto-prostaglandin F1α (6-keto-PF1α) production. The thromboxane/6-keto-PGF1α inhibition ratio (as an indirect index of the prostanoid equilibrium) was 10·8 (se 1) for HT-AC, 1·0 (se 0·1) for HT and 3·3 (se 0·2) for ASA. All three compounds stimulated nitric oxide production, although HT was a weaker effect. In our experiments only concentrations higher than 500 μm (HT) or 1 mm (HT-AC and ASA) inhibited 3-nitrotyrosine production. All three compounds inhibited the production of TNFα by leucocytes, with no significant differences between them. In quantitative terms HT-AC showed a greater antiplatelet aggregating activity than HT and a similar activity to that of ASA. This effect involved a decrease in platelet thromboxane synthesis and an increase in leucocyte nitric oxide production.

This study aimed to evaluate the effects of several minor components of extra virgin olive oil (EVOO) on platelet thromboxane and vascular prostacyclin production in rat aortic rings under high-glucose conditions (300 mg/dL), in relation to their potential antioxidant actions. Under hyperglycaemic conditions, thromboxane production was 1.3 times higher, while prostacyclin production was 40.9% lower than in samples with 100 mg/dL glucose in aortic rings, accompanied by marked oxidative stress (65.6% higher than in samples with 100 mg/dL glucose). The compounds tested inhibited thromboxane production in a concentration-dependent manner, with relative potencies (secoiridoid derivatives (IC50 range: 10−6 M) = triterpenes (10−6 M) > alcoholic phenols (10−5 M for hydroxytyrosol and 10−4 M for the rest)), while preserving prostacyclin production (5–20% inhibition). All compounds also exerted vascular antioxidant effects, reducing oxidative stress markers and enhancing antioxidant parameters (IC50 range: 10−6–10−5 M), and these effects were observed under both normoglycaemic (100 mg/dL) and hyperglycaemic (300 mg/dL) conditions.

The aim of this study is to assess the possible effect of olive seed oil (OSO) and destoned and dehydrated olive oil (DDOO), in comparison with extra-virgin olive oil (EVOO), on some cardiovascular biomarkers in an experimental model of diabetes mellitus. Diabetic animals showed evident alterations in biomarkers involved in the evolution of diabetic vasculopathy, marked by increases in biomarkers that favor vascular damage, which was between 1.5 and five times as many as those in non-diabetic animals, and a smaller number of biomarkers that protect against such damage (25–75% less than in healthy controls) was observed. The three oils administered decreased the concentration of biomarkers of vascular damage (35–45% in the serum lipid profile, 15–40% in early biomarkers of vascular inflammation and 20–60% in platelet aggregation and in thromboxane/prostacyclin imbalance). The greatest effect was by the antioxidant, both in the inhibition of lipid peroxidation and in the increase of glutathione. DDOO showed a significantly greater effect on oxidative stress and on thromboxane/prostacyclin imbalance than those shown by OSO and EVOO. This greater effect may possibly be explained by its higher triterpenoid content (913 mg/kg, compared to 113 mg/kg in OSO and 75 mg/kg in EVOO). We conclude, in the light of the results of this study, that these oils meet two basic conditions: they could improve the yield of the olive industry, and they equal, and may even increase, the beneficial effects of EVOO on cardiovascular disease.

The aim of this study was to determine whether hydroxytyrosol administration prevented kidney damage in an experimental model of type 1 diabetes mellitus in rats. Hydroxytyrosol was administered to streptozotocin-diabetic rats: 1 and 5 mg/kg/day p.o. for two months. After hydroxytyrosol administration, proteinuria was significantly reduced (67–73%), calculated creatinine clearance was significantly increased (26–38%), and the glomerular volume and glomerulosclerosis index were decreased (20–30%). Hydroxytyrosol reduced oxidative and nitrosative stress variables and thromboxane metabolite production. Statistical correlations were found between biochemical and kidney function variables. Oral administration of 1 and 5 mg/kg/day of hydroxytyrosol produced an antioxidant and nephroprotective effect in an experimental model of type 1-like diabetes mellitus. The nephroprotective effect was significantly associated with the systemic and renal antioxidant action of hydroxytyrosol, which also influenced eicosanoid production.

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.

The aim of the present study is to evaluate the possible influence of virgin olive oil (VOO) on the effect of acetylsalicylic acid (ASA) in platelet aggregation, prostanoid and NO production and retinal vascular pattern in rats with experimental type 1-like diabetes. We used 100 male Wistar rats that were distributed into five groups: (1) non-diabetic rats (NDR); (2) untreated diabetic rats (DR); (3) DR treated with ASA (2 mg/kg per d per os (p.o.)); (4) DR treated with VOO (0·5 ml/kg per d p.o.); (5) DR treated with ASA plus VOO. The duration of diabetes was 3 months, and each treatment was administered from the first day of diabetes. Variables that were quantified were platelet aggregation (Imax), thromboxane B2 (TxB2), aortic prostacyclin (6-keto-PGF1α) and NO, and the percentage of retina with horseradish peroxidase-permeable vessels (HRP-PV). Diabetic rats showed a higher Imax (35 %) and TxB2 (63 %) than NDR, and a lower 6-keto-PGF1α, NO and HRP-PV than NDR ( − 74·6 %). ASA and VOO administration reduced these differences and prevented the percentage of HRP-PV ( − 59·7 % with ASA and − 46·7 % with VOO). The administration of ASA plus VOO showed a strong platelet inhibition (80·2 v. 23·4 % for VOO and 50·6 % for ASA+VOO, P < 0·0001), and reduced HRP-PV differences to − 31·6 % (P < 0·001 with respect to DR and P < 0·0001 with respect to DR treated with ASA). In conclusion, the administration of VOO to rats with type 1-like diabetes mellitus improves the pharmacodynamic profile of ASA, and increases its retinal anti-ischaemic effect.

The aim of this study was to assess the effect of triterpenoids on the development of diabetic nephropathy in an experimental model of diabetes mellitus. For this purpose, a destoned and dehydrated olive oil (DDOO) was used, comparing its effects to a destoned olive oil (DOO). DDOO had a higher triterpenoid content than DOO but an equal content of alcoholic polyphenols. Four study groups (n = 10 animals/group) were formed: healthy rats, diabetic control rats (DRs), and DRs treated orally with 0.5 mL/kg/day of DOO or DDOO for two months. DRs showed impaired renal function (proteinuria, increased serum creatinine, decreased renal creatinine clearance) and morphology (glomerular volume and glomerulosclerosis). These alterations correlated with increased systemic and renal tissue oxidative stress and decreased prostacyclin production. DDOO administration significantly reduced all variables of renal damage, as well as systemic and renal oxidative stress, to a greater extent than the effect produced by DOO. In conclusion, triterpenoid-rich olive oil may prevent kidney damage in experimental diabetes mellitus.