Bioactive compounds in pomace olive oil modulate the inflammatory response elicited by postprandial triglyceride-rich lipoproteins in BV-2 cells.

Modulation of microglial response could be a target to reduce neuroinflammation associated with Alzheimer's disease. In this study, we propose that lipophilic bioactive molecules present in pomace olive oil (POO), transported in triglyceride-rich lipoproteins (TRLs), are able to modulate microglial high-oleic sunflower oil (HOSO, points) or pomace olive oil (POO, stripes). In order to prove this hypothesis, a randomized crossover postprandial trial was performed in 18 healthy young women. POO was assayed in opposition to high-oleic sunflower oil (HOSO), a common dietary oil which shares with POO an almost identical fatty acid composition but lacks certain biomolecules with recognized antioxidant and anti-inflammatory activities. TRLs were isolated from blood at the baseline and 2 and 4 hours postprandially and used to treat BV-2 cells to assess their ability to modulate the microglial function. We found that the intake of POO leads to the constitution of postprandial TRLs that are able to modulate the inflammatory response in microglia compared to HOSO. TRL-derived POO reduced the release of pro-inflammatory cytokines (tumor necrosis factor-α, and interleukins 1ß and 6) and nitric oxide and downregulated genes codifying for these cytokines and inducible nitric oxide synthase (iNOS) in BV-2 cells. Moreover, the ingestion of POO by healthy women slightly improved glycemic control and TRL clearance throughout the postprandial phase compared to HOSO. In conclusion, we demonstrated that consuming POO results in postprandial TRLs containing lipophilic bioactive compounds capable of regulating the inflammatory response prompted by microglial activation.

Prognostic Significance of Incidental Deep Vein Thrombosis in Patients with Cancer Presenting with Incidental Pulmonary Embolism.

In symptomatic acute pulmonary embolism (PE), the presence of deep vein thrombosis (DVT) is a risk factor for 30- and 90-day mortality. In patients with cancer and incidental PE, the prognostic effect of concomitant incidental DVT is unknown. In this retrospective study, we examined the effect of incidental DVT on all-cause mortality in such patients. Adjusted Cox multivariate regression analysis was used for relevant covariates. From January 2010 to March 2018, we included 200 patients (mean age, 65.3 ± 12.4 years) who were followed up for 12.5 months (interquartile range 7.4-19.4 months). Of these patients, 62% had metastases, 31% had concomitant incidental DVT, and 40.1% (n = 81) died during follow-up. All-cause mortality did not increase in patients with DVT (hazard ratio [HR] 1.01, 95% confidence interval [CI] 0.43-2.75, p = 0.855). On multivariate analysis, weight (adjusted HR 0.96, 95% CI 0.92-0.99, p = 0.032), and metastasis (adjusted HR 10.26, 95% CI 2.35-44.9, p = 0.002) were predictors of all-cause mortality. In conclusion, low weight and presence of metastases were associated with all-cause mortality, while presence of concomitant DVT was unrelated to poorer survival.

Risk Of Recurrence After Withdrawal Of Anticoagulation In Patients With Unprovoked Venous Thromboembolism: External Validation Of The Vienna Nomogram And The Dash Prediction Score. / Riesgo de recurrencia tras retirada de la anticoagulación en pacientes con enfermedad tromboembólica venosa no provocada: validación externa del nomograma de Viena y del modelo predictivo DASH.

INTRODUCTION: Scales for predicting venous thromboembolism (VTE) recurrence are useful for deciding the duration of the anticoagulant treatment. Although there are several scales, the most appropriate for our setting has not been identified. For this reason, we aimed to validate the DASH prediction score and the Vienna nomogram at 12 months. METHODS: This was a retrospective study of unselected consecutive VTE patients seen between 2006 and 2014. We compared the ability of the DASH score and the Vienna nomogram to predict recurrences of VTE. The validation was performed by stratifying patients as low-risk or high-risk, according to each scale (discrimination) and comparing the observed recurrence with the expected rate (calibration). RESULTS: Of 353 patients evaluated, 195 were analyzed, with an average age of 53.5 ± 19 years. There were 21 recurrences in 1 year (10.8%, 95% CI: 6.8%-16%). According to the DASH score, 42% were classified as low risk, and the rate of VTE recurrence in this group was 4.9% (95% CI: 1.3%-12%) vs. the high-risk group that was 15% (95% CI: 9%-23%) (p <.05). According to the Vienna nomogram, 30% were classified as low risk, and the rate of VTE recurrence in the low risk group vs. the high risk group was 4.2% (95% CI:0.5%-14%) vs. 16.2% (95% CI: 9.9%-24.4%) (p <.05). CONCLUSIONS: Our study validates the DASH score and the Vienna nomogram in our population. The DASH prediction score may be the most advisable, both because of its simplicity and its ability to identify more low-risk patients than the Vienna nomogram (42% vs. 30%).

Enfoque clínico y epidemiológico de pacientes con VIH/sida atendidos en un servicio de urgencias y emergencias / Clinical and epidemiological characterization of patients con HIV/Aids assisted in an urgencies and emergencies service

Se realizó un estudio descriptivo y transversal de 64 pacientes con VIH/sida atendidos en el Servicio de Urgencias y Emergencias del Hospital General Docente Dr Juan Bruno Zayas Alfonso"de Santiago de Cuba, desde enero de 2015 hasta igual mes de 2017, con vistas a caracterizarles según variables clínicas y epidemiológicas de interés para la investigación. En la serie predominaron el sexo masculino, el grupo etario de 15-30 años, la gastritis aguda y la pérdida de conocimiento como causas más frecuentes de atención médica (31,2 y 23,4 por ciento, respectivamente), así como el estado de choque séptico como principal complicación. Se concluye que el sida afecta generalmente a los más jóvenes y las complicaciones graves son bastante frecuentes, aunque la magnitud de las defunciones es baja y la estadía hospitalaria es variable.

A descriptive, cross-sectional and retrospective study of 64 Aids patients assisted at the Urgencies and Emergencies Service of Dr Juan Bruno Zayas Alfonso Teaching General Hospital was carried out in Santiago de Cuba from January, 2015 to the same month in 2017, with the objective of characterizing them according to clinical and epidemiological variables of interest for the investigation. Male sex, the age group 15-30, acute gastritis and the loss of consciousness as the most frequent causes of medical care (31.2 and 23.4 percent, respectively), as well as the septic shock as main complication prevailed in the series . It is concluded that the Aids generally affects the youngest and the severe complications are quite frequent, although the magnitude of the deaths is low and the hospital stay is variable.

Prognosis of patients with syncope seen in the emergency room department: an evaluation of four different risk scores recommended by the European Society of Cardiology guidelines.

AIM: To apply, analyze, and evaluate the four syncope risk scores recommended by the 2009 European guidelines and the different parameters that they use to predict death, syncope recurrence, and hospital readmission in the population seen in the emergency room department (ERD) for syncope. METHODS AND RESULTS: A total of 323 patients aged older than 14 years [mean age 59 (32-75) years] and seen in ERD for syncope over a 2-month period were included in the study; 50.7% were women. Patients were evaluated using the four risk scores and were followed up for at least 2 years. In all, 275 patients (85.2%) were discharged directly from ERD after evaluation. During 28±5 months of follow-up, 8% died, 18.3% presented a further syncopal episode, and 18.6% were readmitted to hospital. Only two of the four risk scores were useful in risk discrimination, but no statistically significant differences were detected between predicted risk and observed risk. Multivariate analysis indicated relationships between age and death, a history of cardiovascular disease and syncope recurrence, and between presyncopal palpitations and hospital readmission. CONCLUSION: Although a large number of events occur after syncope, the risk scores recommended by guidelines overestimate risk, but there were no statistically significant differences between observed and predicted risk.

Brief Communication: Discordant ability of the triglyceride to apolipoprotein B ratio to predict triglyceride-rich lipoprotein particle size in normal-weight and obese men.

The atherogenicity of triglyceride-rich lipoproteins (TRLs) is dependent of their particle size as it determines their metabolic fate. Since TRL possess a single apolipoprotein B (Apo B) molecule per particle, the triglyceride (TG)/Apo B ratio has been used as a convenient method to estimate TRL size. The aim of this study was to validate this approach by correlating the serum TG/Apo B ratio, and the TRL particle size measured by dynamic light scattering (DLS). Twenty-four male volunteers (12 normal-weight and 12 obese individuals) received a high-fat meal. Preprandial (0 h) and postprandial (2 and 4 h) serum samples were collected after meal ingestion, and TRLs were isolated. Serum TG and Apo B levels were quantified, and the TG/Apo B ratio was plotted against TRL particle size measured by DLS for correlation. A strong association between TRL particle size and serum TG/Apo B ratio for normal-weight subjects (P ≤ 0.001) was observed but not for obese subjects (P = 0.6116). TG/Apo B ratio correlates with particle size in healthy normal-weight males but not in obese individuals. Whether this ratio is useful to estimate TRL size in females and in other dyslipidemic patients should be subject of future investigations.

Postprandial phase time influences the uptake of TAG from postprandial TAG-rich lipoproteins by THP-1 macrophages.

Postprandial TAG-rich lipoproteins (TRL) can be taken up by macrophages, leading to the formation of foam cells, probably via receptor-mediated pathways. The present study was conducted to investigate whether the postprandial time point at which TRL are collected modulates this process. A meal containing refined olive oil was given to nine healthy young men and TRL were isolated from their serum at 2, 4 and 6 h postprandially. The lipid class and apoB compositions of TRL were determined by HPLC and SDS-PAGE, respectively. The accumulation of lipids in macrophages was determined after the incubation of THP-1 macrophages with TRL. The gene expression of candidate receptors was measured by real-time PCR. The highest concentrations of TAG, apoB48 and apoB100 in TRL were observed at 2 h after the consumption of the test meal. However, excessive intracellular TAG accumulation in THP-1 macrophages was observed in response to incubation with TRL isolated at 4 h, when their particle size (estimated as the TAG:apoB ratio) was intermediate. The abundance of mRNA transcripts in macrophages in response to incubation with TRL was down-regulated for LDL receptor (LDLR), slightly up-regulated for VLDL receptor and remained unaltered for LDLR-related protein, but no effect of the postprandial time point was observed. In contrast, the mRNA expression of scavenger receptors SRB1, SRA2 and CD36 was higher when cells were incubated with TRL isolated at 4 h after the consumption of the test meal. In conclusion, TRL led to excessive intracellular TAG accumulation in THP-1 macrophages, which was greater when cells were incubated with intermediate-sized postprandial TRL isolated at 4 h and was associated with a significant increase in the mRNA expression of scavenger receptors.

Minor components of olive oil facilitate the triglyceride clearance from postprandial lipoproteins in a polarity-dependent manner in healthy men.

Postprandial triglyceride-rich lipoproteins (TRLs) are recognized as atherogenic particles whose lipid composition and function can be modified by the composition of dietary oils. This study was designed to test the hypothesis that minor components of pomace olive oil (POMACE) can not only change the composition of postprandial TRL but also affect the clearance of triglyceride (TG) molecular species of postprandial TRL. Meals enriched in either POMACE or refined olive oil (OLIVE) were administered to 10 healthy young men. TRL were isolated from serum at 2, 4, and 6 hours postprandially, and their fatty acid and TG molecular species compositions were analyzed by gas chromatography. The apolipoprotein B concentration was determined by immunoturbidimetry. POMACE and OLIVE, differing mainly in their unsaponifiable fraction, led to similar fatty acid and TG molecular species profiles in postprandial TRL. However, POMACE-TRL presented a higher particle size, estimated as TG to apolipoprotein B ratio, which was also found for the main TG molecular species (trioleoyl-glycerol, palmitoyl-dioleoyl-glycerol, palmitoyl-oeloyl-linoleoyl-glycerol, and dioleoyl-linoleoyl-glycerol). TG from POMACE-TRL also showed higher clearance rates. In this regard, apolar TG (with a higher equivalent carbon number) disappeared more rapidly from TRL particles obtained after the ingestion of either POMACE or OLIVE. In conclusion, minor components of POMACE facilitated TG clearance from TRL by modifying their particle size and the hydrolysis of the most apolar species.

Evaluation of the effect of dietary virgin olive oil on blood pressure and lipid composition of serum and low-density lipoprotein in elderly type 2 diabetic subjects.

Dietary virgin olive oil may help to reduce blood pressure in hypertensive individuals, but little is known about the effect on type 2 diabetic patients. For the present study, 17 type 2 diabetic elderly subjects and 23 healthy elderly controls received a diet rich in virgin olive oil for 4 weeks. Blood pressure, biochemical parameters, low-density lipoprotein (LDL), and oxidized LDL lipids and fatty acids were measured. Systolic blood pressure was reduced after virgin olive oil consumption in both controls and diabetic patients. Although the biochemical parameters were not modified, the intervention protected LDL from oxidation and restored the levels of dihomo-gamma-linolenic acid (20:3, n-6) in serum cholesterol esters and phospholipids of diabetic patients. In conclusion, the present study provides new evidence of the effects of dietary virgin olive oil on blood pressure and LDL oxidation in type 2 diabetics. It is likely that the components responsible for the observed effects are the monounsaturated fatty acids and the presence of antioxidants in the oil, but this needs further investigation.

Consumption of virgin olive oil influences membrane lipid composition and regulates intracellular signaling in elderly adults with type 2 diabetes mellitus.

We aimed to define changes in membrane fatty acids and signaling proteins induced by virgin olive oil (VOO) consumption in elderly persons with type 2 diabetes (n = 16) compared to a control group (n = 28). The fatty acid composition was determined by gas chromatography and G-protein subunits and protein kinase C alpha (PKCalpha) by immunoblotting. VOO consumption increased the monounsaturated fatty acid content in phospholipids and cholesterol esters in both groups. In contrast, saturated fatty acids were decreased only in phospholipids. The levels of Galphao, Gbeta, and PKCalpha were significantly lower in diabetics than in controls. However, whereas VOO consumption reduced Galphas, Gbeta, and PKCalpha in both groups, reduction in Galphai was observed only in diabetics. These results indicate that long-term VOO consumption modifies the fatty acid composition of plasma membrane, which influences the association of G proteins and PKCalpha with the lipid bilayer. These combined effects probably account for the positive effects of VOO on glycemic homeostasis.

G protein-coupled receptor systems and their lipid environment in health disorders during aging.

Cells, tissues and organs undergo phenotypic changes and deteriorate as they age. Cell growth arrest and hyporesponsiveness to extrinsic stimuli are all hallmarks of senescent cells. Most such external stimuli received by a cell are processed by two different cell membrane systems: receptor tyrosine kinases (RTKs) and G protein-coupled receptors (GPCRs). GPCRs form the largest gene family in the human genome and they are involved in most relevant physiological functions. Given the changes observed in the expression and activity of GPCRs during aging, it is possible that these receptors are directly involved in aging and certain age-related pathologies. On the other hand, both GPCRs and G proteins are associated with the plasma membrane and since lipid-protein interactions regulate their activity, they can both be considered to be sensitive to the lipid environment. Changes in membrane lipid composition and structure have been described in aged cells and furthermore, these membrane changes have been associated with alterations in GPCR mediated signaling in some of the main health disorders in elderly subjects. Although senescence could be considered a physiologic process, not all aging humans develop the same health disorders. Here, we review the involvement of GPCRs and their lipid environment in the development of the major human pathologies associated with aging such as cancer, neurodegenerative disorders and cardiovascular pathologies.

Virgin olive oil reduces blood pressure in hypertensive elderly subjects.

BACKGROUND & AIMS: Hypertension is one of the most important risk factors for coronary heart disease. Recent studies have pointed out the possibility that virgin olive oil (VOO) may lower blood pressure in hypertensive (HT) subjects. However, until the date there is scarce information regarding elderly people. The present study was designed to assess the effect of dietary VOO on blood pressure in medically treated hypertensive elderly patients. METHODS: 31 medically treated HT elderly patients and 31 normotensive (NT) elderly volunteers participated in a randomized sequential dietary intervention. Subjects consumed diets enriched in sunflower oil (SO) or VOO for 4 weeks each with a 4-week washout period between them. RESULTS: VOO reduced total and LDL-cholesterol in NT but not in HT (P < 0.01) and the concentrations were lower than in the group consuming SO. In contrast, no significant differences were found in the levels of tocopherols among the groups studied. Iron-induced oxidation of LDL resulted in a complete loss of monoacylglycerols (MG) and diacylglycerols (DG) and a reduction in triacylglycerols (TG) (60-80%), which was found to be greater in HT (P < 0.01) with no effect of diet. VOO consumption normalized systolic pressure in the HT group (136 +/- 10 mmHg) compared to SO (150 +/- 8 mmHg). CONCLUSION: Dietary VOO proved to be helpful in reducing the systolic pressure of treated HT elderly subjects. However, a greater resistance to the lowering effect of VOO of total and LDL-cholesterol and a greater susceptibility to TG oxidation was detected in these patients.

Plasma lipid modifications in elderly people after administration of two virgin olive oils of the same variety (Olea europaea var. hojiblanca) with different triacylglycerol composition.

In the present study we examined whether two virgin olive oils (VOO1 and VOO2), of the same variety (Olea europaea var. hojiblanca with a similar composition of minor components but differing in the content of triacylglycerol molecular species, had different effects on blood pressure and plasma lipid levels in a healthy elderly population. Thirty-one participants, aged 84-9 (SD 6.4) years, were asked to participate in the study. No differences were found with regard to blood pressure after both experimental periods (VOO1 and VOO2). However, plasma total cholesterol and LDL-cholesterol were reduced only after VOO1 (P<0.01). The reduction of plasma cholesterol concentrations was related to the incorporation of oleic acid into plasma cholesteryl esters and phospholipids strongly correlated with plasma total cholesterol and LDL-cholesterol levels in all experimental periods studied (r2>0.418, P<0.07), except for phospholipids in VOO1 (P=0.130 for total cholesterol and p=0.360 for LDL-cholesterol). These results have demonstrated that blood pressure and plasma lipids can be modified by the consumption of VOO in elderly people, but that the extent of such modification depends on the composition and amount of active minor components and triacylglycerol molecular species.

Distribution of fatty acids from dietary oils into phospholipid classes of triacylglycerol-rich lipoproteins in healthy subjects.

Several studies have suggested that lipoprotein metabolism can be affected by lipoprotein phospholipid composition. We investigated the effect of virgin olive oil (VOO) and high-oleic sunflower oil (HOSO) intake on the distribution of fatty acids in triacylglycerols (TG), cholesteryl esters (CE) and phospholipid (PL) classes of triacylglycerol-rich lipoproteins (TRL) from normolipidemic males throughout a 7 h postprandial metabolism. Particularly, changes in oleic acid (18:1n-9) concentration of PL were used as a marker of in vivo hydrolysis of TRL external monolayer. Both oils equally promoted the incorporation of oleic acid into the TG and CE of postprandial TRL. However, PL was enriched in oleic acid (18:1n-9) and n-3 polyunsaturated fatty acids (PUFA) after VOO meal, whereas in stearic (18:0) and linoleic (18:2n-6) acids after HOSO meal. We also found that VOO produced TRL which PL 18:1n-9 content was dramatically reduced along the postprandial period. We conclude that the fatty acid composition of PL can be a crucial determinant for the clearance of TRL during the postprandial metabolism of fats.

Triacylglycerol-rich lipoproteins trigger the phosphorylation of extracellular-signal regulated kinases in vascular cells.

Postprandial triacylglycerol-rich lipoproteins (TRL) have been implicated in the pathophysiology of atherosclerosis, but the intracellular processes by which TRL could affect vascular function are still unknown. Incubation of TRL obtained at 2 h postprandial period with vascular smooth muscle cells (VSMC) produced a tyrosine phosphorylation of the extracellular signal-regulated kinases 1 and 2 (ERK1 and ERK2) that belong to the mitogen-activated protein kinase (MAPK) family. The activation of ERK1 and ERK2 had a maximum at 15 min, returned to baseline by 60 min, and was partially depleted after incubation of cells with a MAPKK inhibitor (PD 098059). In addition, postprandial TRL did competent VSMC for DNA replication through a MAPK pathway. These effects were dependent of the lipid composition of TRL. Our observations suggest that postprandial TRL can trigger activation of the MAPK pathway and induce a mitogenic response in VSMC in a lipid-dependent fashion.

Diagnóstico no invasivo de isquemia miocárdica silente en pacientes con factores de alto riesgo coronario / Non-invasive diagnosis of silent myocardial ischemia in patients with high coronary risk factors

Se realizó un estudio explicativo, longitudinal y prospectivo para determinar la incidencia de isquemia miocárdica silente en 76 pacientes de ambos sexos y edades entre 30 y 60 años. Se aplicó un muestreo estratificado, según número de factores de alto riesgo coronario aceptados por la Organización Mundial de la Salud (OMS). Se emplearon la ergometría y el ecocardiograma bidimensional como medios diagnósticos no invasivos. La ergometría resultó ser útil en el 55,4 porciento de los pacientes y el ecocardiograma en el 44,6 porciento, sin diferencias significativas entre ellos. Las diferencias encontradas en cuanto al comportamiento de la isquemia miocárdica silente, según edad y sexo, no resultaron significativas. Se evidenció mayor incidencia en los pacientes con mayor número de factores de alto riesgo coronario con una significación estadística manifiesta. Las arritmias fueron el hallazgo electrocardiográfico basal más frecuente, sin poder atribuírseles valor predictivo diagnóstico de isquemia miocárdica silente