Effects of Virgin Olive Oils Differing in Their Bioactive Compound Contents on Biomarkers of Oxidative Stress and Inflammation in Healthy Adults: A Randomized Double-Blind Controlled Trial.

A regular consumption of virgin olive oil (VOO) is associated with a reduced risk of cardiovascular disease. We aimed to assess whether the raw intake of an optimized VOO (OVOO, 490 ppm of phenolic compounds and 86 ppm of triterpenes), and a functional olive oil (FOO, 487 ppm of phenolic compounds and enriched with 389 ppm of triterpenes) supplementation (30 mL per day) during three weeks would provide additional health benefits to those produced by a standard VOO (124 ppm of phenolic compounds and 86 ppm of triterpenes) on oxidative and inflammatory biomarkers. Fifty-one healthy adults participated in a randomized, crossover, and controlled study. Urinary 8-hidroxy-2'-deoxyguanosine, plasma interleukin-8 (IL-8), and tumor necrosis factor α (TNF- α) concentrations were lower after the intervention with the FOO than after the OVOO (p = 0.033, p = 0.011 and p = 0.020, respectively). In addition, IL-8 was lower after the intervention with FOO than after VOO intervention (p = 0.002). This study provides a first level of evidence on the in vivo health benefits of olive oil triterpenes (oleanolic and maslinic acids) in healthy humans, decreasing DNA oxidation and plasma inflammatory biomarkers. The trial was registered in ClinicalTrials.gov ID: NCT02520739.

Signos, síndromes y enfermedades con nombre propio / Signs, syndromes and diseases with their own names

Se revisan los signos, síndromes y enfermedades con nombre propio más comunes en la medicina interna. Hasta la aparición a mediados del siglo XX de métodos diagnósticos de imagen y no invasivos, la anamnesis y los hallazgos del examen físico del paciente (inspección, palpación, percusión y auscultación) eran la herramienta principal para llegar al diagnóstico de numerosas enfermedades. Por tanto, el incuestionable valor de las nuevas técnicas diagnósticas no puede hacer olvidar el relevante papel del examen clínico. De esta manera, los «descubridores» -Homan, Cushing, Fanconi, entre otros- de ciertos signos clínicos, síndromes o entidades morbosas siguen en la actualidad conservando su predicamento. El talento y el «ojo clínico» permitieron a galenos talentosos reconocer enfermedades ocultas que, de otra forma, se habrían mantenido ignoradas durante largo tiempo

A review is presented of the most common signs, syndromes and diseases bearing the name of their discoverers. Until imaging and non-invasive diagnostic procedures appeared by the second half of the 20th century, diagnosis was mainly established by anamnesis and physical examination of the patients by inspection, palpation, percussion, and auscultation. However, the unquestionable value of these findings should not relegate the clinical examination. Therefore, many signs of syndromes and disease have taken the name of their discoverers: Homan, Cushing, Fanconi, among others, are still current and useful despite the innovative diagnostic tolos

Alfred Nobel y la medicina / Alfred Nobel and the medicine

Alfred Nobel dedicó su vida a la industria y la investigación como ingeniero, químico y descubridor de la dinamita. Su espíritu pacifista le llevó a emplear su fortuna (33 millones de coronas) en los premios que llevan su nombre. En 1901 se otorgó el primero a Emil Adolph von Behring, por el descubrimiento del suero antidiftérico. Desde entonces se ha concedido anualmente, salvo en los años de guerras mundiales (1914-1918 y 1939-1945 respectivamente). Los descubrimientos de Alfred Nobel estaban orientados a mejorar las comunicaciones: ferrocarriles, puertos, túneles, puentes y otras vías; pero él nunca imaginó que sus inventos se utilizarían con fines bélicos y homicidas. Han transcurrido 121 años desde su muerte y su nombre es conocido en todo el mundo gracias a los premios por él instaurados. Respecto a la medicina, hasta hoy, han sido 208 investigadores los laureados, término que la Fundación Nobel gusta emplear

Alfred Nobel devoted his life to the industry and research as an engineer, chemist, and was the discoverer of dynamite. His pacifist spirit led him to devote his fortune (33 million Swedish Kroner) to the awards that bear his name. The first Prize was awarded to Emil Adolph von Behring in recognition of his studies on diphtheria. Since then, the prize has been given annually, except during the first (1914-1918) and second World Wars (1939-1945), respectively. His findings were aimed at improving terrestrial communications such as railways, seaports, dams, tunnels, bridges, and other road networks. However, he never thought his discoveries would be used for military purposes. As 121 years have elapsed since this important "Maecenas", whose name has spread across the world. As regards medicine, there are currently 208 Nobel Laureates, a term used by the Nobel Foundation

Effects of Virgin Olive Oils Differing in Their Bioactive Compound Contents on Metabolic Syndrome and Endothelial Functional Risk Biomarkers in Healthy Adults: A Randomized Double-Blind Controlled Trial.

The aim of this study was to evaluate the effect of virgin olive oils (VOOs) enriched with phenolic compounds and triterpenes on metabolic syndrome and endothelial function biomarkers in healthy adults. The trial was a three-week randomized, crossover, controlled, double-blind, intervention study involving 58 subjects supplemented with a daily dose (30 mL) of three oils: (1) a VOO (124 ppm of phenolic compounds and 86 ppm of triterpenes); (2) an optimized VOO (OVOO) (490 ppm of phenolic compounds and 86 ppm of triterpenes); and (3) a functional olive oil (FOO) high in phenolic compounds (487 ppm) and enriched with triterpenes (389 ppm). Metabolic syndrome and endothelial function biomarkers were determined in vivo and ex vivo. Plasma high density lipoprotein cholesterol (HDLc) increased after the OVOO intake. Plasma endothelin-1 levels decreased after the intake of the three olive oils, and in blood cell cultures challenged. Daily intake of VOO enriched in phenolic compounds improved plasma HDLc, although no differences were found at the end of the three interventions, while VOO with at least 124 ppm of phenolic compounds, regardless of the triterpenes content improved the systemic endothelin-1 levels in vivo and ex vivo. No effect of triterpenes was observed after three weeks of interventions. Results need to be confirmed in subjects with metabolic syndrome and impaired endothelial function (Clinical Trials number NCT02520739).

El correcto empleo del español / The correct use of Spanish

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A Study to Investigate the Efficacy and Safety of an Anti-Interleukin-18 Monoclonal Antibody in the Treatment of Type 2 Diabetes Mellitus.

OBJECTIVE: Evidence suggests that chronic subclinical inflammation plays an important role in the pathogenesis of type 2 diabetes (T2DM). Circulating levels of interleukin (IL)-18 appear to be associated with a number of micro- and macrovascular comorbidities of obesity and T2DM. This study was designed to investigate whether inhibition of IL-18 had any therapeutic benefit in the treatment of T2DM. Preliminary efficacy, safety and tolerability, pharmacokinetics, and pharmacodynamics of the anti-IL-18 monoclonal antibody, GSK1070806, were assessed. RESEARCH DESIGN AND METHODS: This was a multicentre, randomized, single-blind (sponsor-unblinded), placebo-controlled, parallel-group, phase IIa trial. Obese patients of either sex, aged 18-70 years, with poorly controlled T2DM on metformin monotherapy were recruited. Patients received two doses, of placebo (n = 12), GSK1070806 0.25 mg/kg (n = 13) or GSK1070806 5 mg/kg (n = 12). The primary end-point was the change from baseline in fasting plasma glucose and weighted mean glucose area under the curve (AUC)(0-4 hours) postmixed meal test on Days 29, 57, and 85. RESULTS: Thirty-seven patients were randomized to one of the three treatment arms. There were no statistically significant effects of GSK1070806 doses on fasting plasma glucose levels, or weighted mean glucose AUC(0-4 hours) compared with placebo. CONCLUSIONS: GSK1070806 was well tolerated, and inhibition of IL-18 did not lead to any improvements in glucose control. However, because of study limitations, smaller, potentially clinically meaningful effects of IL-18 inhibition cannot be excluded. TRIAL REGISTRATION: ClinicalTrials.gov NCT01648153.

Nifedipine plus candesartan combination increases blood pressure control regardless of race and improves the side effect profile: DISTINCT randomized trial results.

OBJECTIVES: DISTINCT (reDefining Intervention with Studies Testing Innovative Nifedipine GITS - Candesartan Therapy) aimed to determine the dose-response and tolerability of nifedipine GITS and/or candesartan cilexetil therapy in participants with hypertension. METHODS: In this 8-week, multinational, multicentre, randomized, double-blind, placebo-controlled study, adults with mean seated DBP of at least 95 to less than 110 mmHg received combination or monotherapy with nifedipine GITS (N) 20, 30 or 60 mg and candesartan cilexetil (C) 4, 8, 16 or 32 mg, or placebo. The primary endpoint, change in DBP from baseline to Week 8, was analysed using the response surface model (RSM); this analysis was repeated for mean seated SBP. RESULTS: Overall, 1381 participants (mean baseline SBP/DBP: 156.5/99.6 mmHg) were randomized. Both N and C contributed independently to SBP/DBP reductions [P < 0.0001 (RSM)]. A positive dose-response was observed, with all combinations providing statistically better blood pressure (BP) reductions from baseline versus respective monotherapies (P < 0.05) and N60C32 achieving the greatest reduction [-23.8/-16.5 mmHg; P < 0.01 versus placebo (-5.3/-6.7 mmHg) and component monotherapies]. Even very low-dose (N20 and C4) therapy provided significant BP-lowering, and combination therapy was similarly effective in different racial groups. N/C combination demonstrated a lower incidence of vasodilatory adverse events than N monotherapy (18.3 versus 23.6%), including headache (5.5 versus 11.0%; P = 0.003, chi-square test) and peripheral oedema over time (3.6 versus 5.8%; n.s.). CONCLUSION: N/C combination was effective in participants with hypertension and showed an improved side effect profile compared with N monotherapy.

Ambulatory blood pressure monitoring in the elderly.

The incidence of hypertension is high in the elderly and is present in 2/3 of the patients older than 65 years. Prevalence can reach 90% in patients older than 80 years. The presence of isolated systolic hypertension (ISH) is characteristic of this population. However, the prevalence of hypertension by ambulatory blood pressure monitoring (ABPM) is not well known. In this study, we analyzed the special characteristics of hypertension in this population, giving special emphasis on ABPM readings.

Lipid disorders in elderly hypertensive patients.

Lipid disorders are a common clinical challenge in the western countries. In patients with dyslipemia (total cholesterol > 200 mg/dl, HDL cholesterol < 35 mg/dl, LDL cholesterol > 130 mg/dl and triglycerides > 150 mg/dl) it is mandatory to normalize blood pressure (<130/80 mmHg) as well to reduce LDL-C values to normal levels by using drugs to inhibit of endogenous and exogenous cholesterol, to decrease triglycerides, and increases HDL-C up to normal range. It is also essential to maintain for this purpose suitable dietetic measures (reduction of unsatured fats and salt intakes-<2.5 g/daily) and without interruption, to support pharmacologic treatment in most of the patients.

Hypertension in the elderly.

Background. The incidence of hypertension in the Western countries is continuously increasing in the elderly population and remains the leading cause of cardiovascular and morbidity. Methods. we analysed some significant clinical trials in order to present the relevant findings on those hypertensive population. Results. Several studies (SYST-EUR, HYVET, CONVINCE, VALUE, etc.) have demonstrated the benefits of treatment (nitrendipine, hydrochrotiazyde, perindopril, indapamide, verapamil, or valsartan) in aged hypertensive patients not only concerning blood pressure values but also the other important risk factors. Conclusion. Hypertension is the most prevalent cardiovascular disorder in the Western countries, and the relevance of receiving pharmacological treatment of hypertension in aged patients is crucial; in addition, the results suggest that combination therapy-nitrendipine plus enalapril-could have more benefits than those observed with the use of nitrendipine alone.

The effect of treatment based on a diuretic (indapamide) +/- ACE inhibitor (perindopril) on fractures in the Hypertension in the Very Elderly Trial (HYVET).

BACKGROUND: fractures may have serious implications in an elderly individual, and fracture prevention may include a careful choice of medications. DESIGN: the Hypertension in the Very Elderly Trial (HYVET) was a double-blind placebo-controlled trial of a thiazide-like diuretic (indapamide 1.5 mg SR) with the optional addition of the angiotensin-converting enzyme (ACE) inhibitor (perindopril 2-4 mg). Fracture was a secondary end point of the trial. SETTING: HYVET recruited participants from Eastern and Western Europe, China, Australasia, and Tunisia. SUBJECTS: all participants were > or =80 years of age and hypertensive. METHODS: participants were randomised to receive a thiazide-like diuretic (indapamide 1.5 mg SR) +/- ACE inhibitor (perindopril 2-4 mg) or matching placebos. Incident fractures were validated and analysed based on time to first fracture. RESULTS: there were 3,845 participants in HYVET and a total 102 reported fractures (42 in the active and 60 in the placebo group). When taking only validated first fractures, 90 were included in the analyses (38 in the active and 52 in the placebo group). Cox proportional hazard regression, adjusted for key baseline risk factors, resulted in a point estimate of 0.58 (95% CI 0.33-1.00, P = 0.0498). CONCLUSIONS: despite the lowering of blood pressure, treatment with a thiazide-like diuretic and an ACE inhibitor does not increase and may decrease fracture rate.

Tratamiento del paciente de 80 o más años con hipertensión arterial / No disponible

No disponible

Efficacy and safety of the coadministration of ezetimibe/simvastatin with fenofibrate in patients with mixed hyperlipidemia.

BACKGROUND: Mixed hyperlipidemia is characterized by elevated low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), and TG-rich lipoprotein levels. METHODS: In a multicenter, randomized, double-blind, placebo-controlled, parallel arm trial, eligible patients were 18 to 79 years of age, with mixed hyperlipidemia (LDL-C 130-220 mg/dL, TG 150-500 mg/dL). Patients with type 2 diabetes were limited to those with LDL-C of 100 to 180 mg/dL. Patients (N = 611) were randomized in a 3:3:3:1 ratio to one of 4 treatment arms for 12 weeks: ezetimibe/simvastatin 10/20 mg (EZE/SIMVA) + fenofibrate 160 mg (FENO), EZE/SIMVA 10/20 mg, FENO 160 mg, or placebo. The primary objective was to evaluate the LDL-C-lowering efficacy of EZE/SIMVA + FENO versus FENO monotherapy. RESULTS: Low-density lipoprotein cholesterol level was significantly (P < .05) reduced with EZE/SIMVA + FENO (-45.8%) compared with FENO (-15.7%) or placebo (-3.5%), but not when compared with EZE/SIMVA (-47.1%). High-density lipoprotein cholesterol and apolipoprotein A-I levels were significantly increased with EZE/SIMVA + FENO (18.7% and 11.1%, respectively) treatment compared with EZE/SIMVA (9.3% and 6.6%) or placebo (1.1% and 1.6%), but not when compared with FENO (18.2% and 10.8%). Triglyceride, non-high-density lipoprotein cholesterol, and apolipoprotein B levels were significantly reduced with EZE/SIMVA + FENO (-50.0%, -50.5%, and -44.7%, respectively) versus all other treatments. Treatment with EZE/SIMVA + FENO was generally well tolerated with a safety profile similar to the EZE/SIMVA and FENO therapies. CONCLUSIONS: Coadministration of EZE/SIMVA + FENO effectively improved the overall atherogenic lipid profile of patients with mixed hyperlipidemia. Clinical trial registry number: NCT 00093899 (http://www.ClinicalTrials.gov).

Efficacy and safety of ezetimibe/simvastatin co- administered with fenofibrate in mixed hyperlipidemic patients with metabolic syndrome.

BACKGROUND: We compared the lipid-altering effects of ezetimibe/simvastatin (EZE/SIMVA) co-administered with fenofibrate (FENO) in mixed hyperlipidemic patients with (MetS) versus those without MetS. METHODS: A total of 611 patients, 20 to 79 years old, with LDL-C 130-220 mg/dL (100-180 mg/dL for patients with type 2 diabetes [T2D]), triglycerides (TG) 150-500 mg/dL, and no history of CHD or other CHD risk equivalent disease (except for T2D), were randomized in a 1:3:3:3 ratio into one of the following four treatments for 12 weeks: placebo; EZE/SIMVA 10/20 mg; FENO 160 mg; or EZE/SIMVA+FENO. MetS status was determined in 607 patients using National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria. Percentage change from baseline in low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-HDL-C, total cholesterol (TC), TG, apolipoproteins A-I and B, and C-reactive protein was assessed in these patients with or without MetS. The primary objective was to evaluate the lipid-altering efficacy of EZE/SIMVA+FENO versus FENO monotherapy in the MetS versus non-MetS subgroups. RESULTS: At baseline, patients with MetS had a higher body mass index (BMI) and TG and lower HDL-C. At Week 12, treatment with EZE/SIMVA, FENO, and EZE/SIMVA + FENO led to similar improvements in lipid parameters in patients with MetS compared to those without MetS. Treatment with EZE/SIMVA + FENO and FENO also led to an increase in LDL particle-size pattern after 12 weeks in both subgroups of patients. CONCLUSIONS: This post-hoc analysis suggested that co-administration of EZE/SIMVA+FENO had consistent benefits on the lipid profile in mixed hyperlipidemic patients with or without MetS.

Doxazosin GITS versus standard doxazosin in mild to moderate hypertension.

BACKGROUND: The selective alpha 1-adrenoceptor antagonist doxazosin in both standard formulation and gastrointestinal therapeutic system (GITS) controlled-release formulation is effective for hypertension without having a negative impact on serum lipids. This study was designed to compare the relative efficacy of these two formulations of doxazosin on clinic and ambulatory blood pressure and serum lipids in patients with mild to moderate hypertension. METHODS: Hypertensive patients aged 18-70 years (n = 335) were evaluated in a multi-center prospective randomized study. Following a 2-week placebo run-in phase, patients were randomized to receive doxazosin 2 or 4 mg, with dose titration, or doxazosin GITS 4 mg, no dose titration, for 9 weeks. RESULTS: Both doxazosin formulations reduced clinic diastolic and systolic blood pressure from baseline (P < 0.0001). Doxazosin GITS and doxazosin 4 mg had similar blood pressure-lowering effects. Doxazosin GITS reduced sitting diastolic and systolic blood pressure compared with doxazosin 2 mg (P < 0.01 for both). A greater proportion of the doxazosin GITS group reached goal blood pressure (< or = 140/90 mm Hg) after 9 weeks compared with the doxazosin 2-mg group. All doses of doxazosin reduced 24-h and daytime (7:00 am to 10:00 pm) ambulatory blood pressure from baseline (all P < 0.01). Doxazosin GITS significantly reduced nighttime (10:00 pm to 7:00 am) ambulatory blood pressure from baseline. A neutral effect on serum lipids was observed with doxazosin. CONCLUSIONS: Doxazosin GITS and doxazosin were effective in reducing clinic and ambulatory blood pressure. The GITS formulation reduced the need for dose titration. Both doxazosin formulations were well tolerated.

Results of the pilot study for the Hypertension in the Very Elderly Trial.

BACKGROUND: The risks and benefits of treating hypertension in individuals older than 80 years are uncertain. A meta-analysis has suggested that a reduction in stroke events of 36% may have to be balanced against a 14% increase in total mortality. OBJECTIVES: To report the results of the pilot study of the Hypertension in the Very Elderly Trial (HYVET), which is in progress to address these issues. METHODS: The HYVET-Pilot was a multicentre international open pilot trial. In 10 European countries, 1283 patients older than 80 years and with a sustained blood pressure of 160-219/90-109 mmHg were allocated randomly to one of three treatments: a diuretic-based regimen (usually bendroflumethiazide; n = 426), an angiotensin-converting enzyme inhibitor regimen (usually lisinopril; n = 431) or no treatment (n = 426). The procedure permitted doses of the drug to be titrated and diltiazem slow-release to be added to active treatment. Target blood pressure was < 150/80 mmHg and mean follow-up was 13 months. RESULTS: In the combined actively treated groups, the reduction in stroke events relative hazard rate (RHR) was 0.47 [95% confidence interval (CI) 0.24 to 0.93] and the reduction in stroke mortality RHR was 0.57 (95% CI 0.25 to 1.32). However, the estimate of total mortality supported the possibility of excess deaths with active treatment (RHR 1.23, 95% CI 0.75 to 2.01). CONCLUSIONS: The preliminary results support the need for the continuing main HYVET trial. It is possible that treatment of 1000 patients for 1 year may reduce stroke events by 19 (nine non-fatal), but may be associated with 20 extra non-stroke deaths.

The prevention of dementia with antihypertensive treatment: new evidence from the Systolic Hypertension in Europe (Syst-Eur) study.

BACKGROUND: After the double-blind, placebo-controlled Systolic Hypertension in Europe (Syst-Eur) trial ended in February 1997, randomized patients were offered active study medication for a further period of observation. OBJECTIVE: To refine the estimates of the long-term effects of antihypertensive therapy on the incidence of dementia. METHODS: Eligible patients had no dementia and were at least 60 years old. Their systolic blood pressure at entry was 160 to 219 mm Hg, with diastolic blood pressure below 95 mm Hg. Antihypertensive therapy was started immediately after randomization in the active treatment group, but only after termination of the double-blind trial in the control patients. Treatment consisted of nitrendipine (10-40 mg/d), with the possible addition of enalapril maleate (5-20 mg/d), hydrochlorothiazide (12.5-25 mg/d), or both add-on drugs. RESULTS: Median follow-up increased from 2.0 years in the double-blind trial to 3.9 years overall. The incidence of dementia doubled from 32 to 64 cases, 41 of whom had Alzheimer disease. Throughout follow-up, systolic/diastolic blood pressure was 7.0/3.2 mm Hg higher in the 1417 control patients than in the 1485 subjects randomized to active treatment. At the last examination, the blood pressure difference was still 4.2/2.9 mm Hg; 48.1%, 26.4%, and 11.4% of the control patients were taking nitrendipine, enalapril, and/or hydrochlorothiazide, whereas in the active treatment group these proportions were 70.2%, 35.4%, and 18.4%, respectively. Compared with the controls, long-term antihypertensive therapy reduced the risk of dementia by 55%, from 7.4 to 3.3 cases per 1000 patient-years (43 vs 21 cases, P<.001). After adjustment for sex, age, education, and entry blood pressure, the relative hazard rate associated with the use of nitrendipine was 0.38 (95% confidence interval, 0.23-0.64; P<.001). Treatment of 1000 patients for 5 years can prevent 20 cases of dementia (95% confidence interval, 7-33). CONCLUSION: The extended follow-up of Syst-Eur patients reinforces the evidence that blood pressure-lowering therapy initiated with a long-acting dihydropyridine protects against dementia in older patients with systolic hypertension.

Endothelins and markers of renal damage in recently diagnosed hypertensive patients.

Endothelin has been identified as a potent vasoconstrictor. The aim of this study was to evaluate urinary endothelins and their relation to other markers of renal damage, such as microalbuminuria, creatinine, and N-acetyl-beta-glucosaminidase (NAG), in a group of recently diagnosed (less than 1 year) hypertensive subjects and a control group. We selected 50 subjects and divided them into two groups: 27 hypertensive patients (15 females and 12 males) without previous pharmacologic therapy, and 23 healthy, normotensive subjects (12 females and 11 males). All patients underwent a history and physical examination, chest x-ray, electrocardiography, funduscopy, and hematologic and biochemical analyses. Endothelins, microalbuminuria, creatinine, and NAG values were also determined in 24-hour urine samples. Creatinine, microalbuminuria, and NAG values were found to be higher in hypertensive than in normotensive subjects. The hypertensive group showed a nonsignificant elevation of total endothelin. In conclusion, the determination of elevated urinary endothelin does not appear to be an early marker of organ damage in hypertensive subjects. The urinary excretion of protein, creatinine, and NAG was higher in hypertensive subjects. A positive correlation was found between the urinary excretion of endothelins and markers of renal damage, microalbuminuria and NAG values. The relationship between endothelins and hypertension was without statistical significance.