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.

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.

Synergistic Effect of 3',4'-Dihidroxifenilglicol and Hydroxytyrosol on Oxidative and Nitrosative Stress and Some Cardiovascular Biomarkers in an Experimental Model of Type 1 Diabetes Mellitus.

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.

Nephroprotective Effect of the Virgin Olive Oil Polyphenol Hydroxytyrosol in Type 1-like Experimental Diabetes Mellitus: Relationships with Its Antioxidant Effect.

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.

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.

Factores de predicción de dosificación inadecuada de rivaroxabán utilizando la ecuación de CKD-EPI / Rivaroxaban Inappropriate Dosage Predictor Factors Using The Ckd-Epi Equation

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TIMI-AF score and cardiovascular events in vitamin K antagonists-naïve outpatients with atrial fibrillation.

BACKGROUND: The TIMI-AF score predicts poor outcomes in patients with atrial fibrillation (AF) and guides selection of anticoagulant therapy by identifying clinical benefit of direct oral anticoagulants (DOACs) or vitamin K antagonists (VKA). HYPOTHESIS: Our objective was to determine the ability to predict cardiovascular events according to the TIMI-AF score in a real-world population. METHODS: Retrospective observational study of VKA-naïve patients with AF was seen at a cardiology outpatient clinic in Spain between November 2012 and August 2014. We recorded adverse events (myocardial infarction, systemic embolism or stroke, major bleeding, and death). RESULTS: The study population comprised of 426 patients (50.7% men, mean age, 69 ± 14 years). The TIMI-AF score identified 372 patients (87.3%) with a low risk, 50 patients (11.7%) with an intermediate risk, and 4 patients (0.9%) with a high risk. After a mean follow-up of 423.4 ± 200.1 days, 37 patients (9%) experienced an adverse event. Patients with a TIMI-AF score ≥ 7 had a poorer cardiovascular prognosis (HR, 6.1; 95%CI, 3.2-11.7; P < 0.001). The area under the ROC curve of TIMI-AF was 0.755 (95%CI, 0.669-0.840; P < 0.001), which was greater than that of CHA2 DS2 VASc (0.641; 95%CI, 0.559-0.724; P = 0.004), HAS-BLED (0.666; 95%CI, 0.578-0.755; P < 0.001), and SAMeTT2 R2 (0.529; 95%CI, 0.422-0.636; P = 0.565). Similar results were obtained in relation to the net clinical outcome (life-threatening bleeding, disabling stroke, or all-cause mortality). CONCLUSIONS: The TIMI-AF risk score can identify patients who are at greater risk of cardiovascular events and a poor net clinical outcome with a better diagnostic yield than CHA2 DS2 VASc, HAS-BLED, and SAMeTT2 R2 .

Drug persistence and outcomes in a cohort of patients with nonvalvular atrial fibrillation treated with rivaroxaban after 2 years of follow-up in clinical practice.

AIM: To evaluate medication persistence and outcomes in patients with atrial fibrillation after 2 years of treatment with rivaroxaban in routine practice. METHODS: Retrospective study of atrial fibrillation patients in whom rivaroxaban was prescribed during the first quarter of 2014 in the healthcare area of Costa del Sol (Málaga). RESULTS: A total of 111 patients (mean age 74.9 ± 10.9 years; 52.3% men; CHA2DS2-VASc 3.6 ± 1.3; HAS-BLED 1.3 ± 0.6) were included. A total of 96.3 and 90.6% of patients remained on rivaroxaban therapy after 1 and 2 years of treatment, respectively. During this period, stroke, net clinical benefit outcome (thromboembolic events, myocardial infarction, cardiovascular death and major bleeding) and cardiovascular death occurred in 3.6, 5.4 and 1.8% of patients, respectively. CONCLUSION: In routine practice, medication persistence with rivaroxaban was high. Rates of major cardiac events were low.

Discrepancias entre el empleo de las ecuaciones MDRD-4 IDMS y CKD-EPI en vez de la de Cockcroft-Gault en la determinación de la posología de los anticoagulantes orales directos en pacientes con fibrilación auricular no valvular / Discrepancies between the use of MDRD-4 IDMS and CKD-EPI equations, instead of the Cockcroft-Gault equation, in the determination of the dosage of direct oral anticoagulants in patients with non-valvular atrial fibrillation

Fundamento y objetivo: Los anticoagulantes orales directos (ACOD) precisan ajuste de dosis según el estimated clearance creatinine (eClCr, «aclaramiento de creatinina estimado») por la ecuación de Cockcroft-Gault (CG). Existen discrepancias entre las ecuaciones que estiman el filtrado glomerular (FGe). Analizamos cómo afecta a la posología recomendada para los ACOD el empleo de las ecuaciones CKD-EPI y MDRD-4 IDMS. Pacientes y métodos: Estudio retrospectivo de pacientes con fibrilación auricular no valvular atendidos en una consulta de cardiología entre noviembre de 2012 y agosto de 2014. Se reclasifican los pacientes según la posología recomendada para dabigatrán, rivaroxabán, apixabán y edoxabán en función de la ecuación de FGe empleada. Se tienen en cuenta otros factores clínicos, según ficha técnica. Analizamos el porcentaje de discordancia. Resultados: Se estudian 454 pacientes, 53,3% hombres, con una edad media de 68,7±13,8 años. La media de las diferencias intraindividuales registradas respecto a la ecuación de GC fue de 3,9ml/min/1,73m2 con MDRD-4 IDMS (IC 95% 1,4-6,4; p=0,003) y 11,3ml/min/1,73m2 con CKD-EPI (IC 95% 8,9-13,7; p<0,001). Se observa un gradiente en la discordancia de la posología (apixabán 1,1%, dabigatrán 3,5%, edoxabán 5,7%, rivaroxabán 8,4% con MDRD-4 IDMS). Las diferencias se limitaron a los pacientes con eClCr<60ml/min y fueron más manifiestas en≥75 años, en los que las ecuaciones de FGe sobreestiman la función renal. Conclusiones: En pacientes con fibrilación auricular no valvular, especialmente con insuficiencia renal y en ancianos, las ecuaciones de FGe tienden a sobreestimar la función renal respecto a CG y, por ello, a recomendar una sobredosificación de los ACOD (AU)

Background and objective: Direct oral anticoagulants (DOACs) require dose adjustment according to estimated clearance creatinine (eClCr) using the Cockcroft-Gault (CG) equation. There are discrepancies with the equations that estimate glomerular filtration rate (eGFR). We analyse how the use of the CKD-EPI and MDRD-4 IDMS equations affect the recommended dosage for ACODs. Patients and methods: Retrospective study of patients with non-valvular atrial fibrillation seen at a cardiology clinic between November 2012 and August 2014. Patients were reclassified according to the recommended dosage for dabigatran, rivaroxaban, apixaban and edoxaban, based on the eGFR equation used. Other clinical factors are taken into account, according to the product label. We analysed the percentage of discordance. Results: Four hundred and fifty-four patients, 53.3% men, with a mean age of 68.7±13.8 years were studied. The mean intra-individual differences recorded for the CG equation were 3.9ml/min/1.73m2 with MDRD-4 IDMS (95% CI 1.4-6.4, P=.003) and 11.3ml/min/1.73m2 with CKD-EPI (95% CI 8.9-13.7, P<.001). A gradient is observed in the discordance of the posology (apixaban 1.1%, dabigatran 3.5%, edoxaban 5.7%, rivaroxaban 8.4% with MDRD-4 IDMS). Differences were limited to patients with eClCr<60ml/min and were more evident in≥75 years in which the eGFR equations overestimate renal function. Conclusions: In patients with non-valvular atrial fibrillation, especially with renal failure and in the elderly, eGFR equations tend to overestimate renal function relative to CG and therefore suggest an overdose of DOACs (AU)

Neuroprotective Effect of Hydroxytyrosol in Experimental Diabetic Retinopathy: Relationship with Cardiovascular Biomarkers.

The aim of the study was to test the neuroprotective effect of hydroxytyrosol (HT) on experimental diabetic retinopathy. Animals were divided in four groups: (1) control nondiabetic rats, (2) streptozotocin-diabetic rats (DR), (3) DR treated with 1 mg/kg/day p.o. HT, and (4) DR treated with 5 mg/kg/day p.o. HT. Treatment with HT was started 7 days before inducing diabetes and was maintained for 2 months. In the DR group, total area occupied by extracellular matrix was increased, area occupied by retinal cells was decreased; both returned to near-control values in DR rats treated with HT. The number of retinal ganglion cells in DR was significantly lower (44%) than in the control group, and this decrease was smaller after HT treatment (34% and 9.1%). Linear regression analysis showed that prostacyclin, platelet aggregation, peroxynitrites, and the dose of 5 mg/kg/day HT significantly influenced retinal ganglion cell count. In conclusion, HT exerted a neuroprotective effect on diabetic retinopathy, and this effect correlated significantly with changes in some cardiovascular biomarkers.

Prevalence and Related Factors of Ineffective Self-Health Management in Polymedicated Patients Over the Age of 65 Years.

PURPOSE: To determine the prevalence of Ineffective Self-Health Management (ISHM) (00078) and its related factors in polymedicated patients over the age of 65 years. METHODS: A cross-sectional, descriptive design was used. A home interview was conducted with each participant (N = 375) for data collection. FINDINGS: The prevalence of ISHM was 37.3%. The risk factors associated were social risk, depression, noncompliance, medication errors, and confusion with medications. CONCLUSIONS: Among polymedicated elderly patients, the prevalence of ISHM is high. The diagnosis is closely connected to the compliance and complexity of the treatment regimen, in addition to those relating strictly to social and emotional factors. IMPLICATIONS: Nursing methodology encompasses instruments that allow nurses in clinical practice to evaluate the issue of compliance.

Discrepancies between the use of MDRD-4 IDMS and CKD-EPI equations, instead of the Cockcroft-Gault equation, in the determination of the dosage of direct oral anticoagulants in patients with non-valvular atrial fibrillation. / Discrepancias entre el empleo de las ecuaciones MDRD-4 IDMS y CKD-EPI en vez de la de Cockcroft-Gault en la determinación de la posología de los anticoagulantes orales directos en pacientes con fibrilación auricular no valvular.

BACKGROUND AND OBJECTIVE: Direct oral anticoagulants (DOACs) require dose adjustment according to estimated clearance creatinine (eClCr) using the Cockcroft-Gault (CG) equation. There are discrepancies with the equations that estimate glomerular filtration rate (eGFR). We analyse how the use of the CKD-EPI and MDRD-4 IDMS equations affect the recommended dosage for ACODs. PATIENTS AND METHODS: Retrospective study of patients with non-valvular atrial fibrillation seen at a cardiology clinic between November 2012 and August 2014. Patients were reclassified according to the recommended dosage for dabigatran, rivaroxaban, apixaban and edoxaban, based on the eGFR equation used. Other clinical factors are taken into account, according to the product label. We analysed the percentage of discordance. RESULTS: Four hundred and fifty-four patients, 53.3% men, with a mean age of 68.7±13.8 years were studied. The mean intra-individual differences recorded for the CG equation were 3.9ml/min/1.73m2 with MDRD-4 IDMS (95% CI 1.4-6.4, P=.003) and 11.3ml/min/1.73m2 with CKD-EPI (95% CI 8.9-13.7, P<.001). A gradient is observed in the discordance of the posology (apixaban 1.1%, dabigatran 3.5%, edoxaban 5.7%, rivaroxaban 8.4% with MDRD-4 IDMS). Differences were limited to patients with eClCr<60ml/min and were more evident in≥75 years in which the eGFR equations overestimate renal function. CONCLUSIONS: In patients with non-valvular atrial fibrillation, especially with renal failure and in the elderly, eGFR equations tend to overestimate renal function relative to CG and therefore suggest an overdose of DOACs.

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

METHODS AND DESIGN: 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. RESULTS: 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 (ß = 14.27 p < 0.001) with better health-related quality of life, while illiteracy (ß = -13.58 p < 0.001), depression (ß = -10.13 p < 0.001), social risk (ß = -7.23 p = 0.004) and using more than 10 medicines (ß = -4.85 p = 0.009) were strongly associated with a poorer health-related quality of life. CONCLUSIONS: 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.

Neuroprotective Effect of Hydroxytyrosol in Experimental Diabetes Mellitus.

The aim of the study was to analyze the possible neuroprotective effect of hydroxytyrosol (HT) in diabetic animals in a model of hypoxia-reoxygenation. Rats (10 animals/group) were distributed in five groups: nondiabetic rats, control diabetic rats (DR), and DR rats treated for 2 months with 1, 5, or 10 mg/kg/day po HT. At the end of follow-up, an experimental model of hypoxia-reoxygenation in brain slices was tested. The DR group showed increased cell death, oxidative and nitrosative stress, and an increase in brain inflammatory mediators. These alterations were significantly greater in DR than in normoglycemic animals. HT significantly reduced oxidative (38.5-52.4% lipid peroxidation) and nitrosative stress (48.0-51.0% nitric oxide and 43.9-75.2% peroxynitrite concentration) and brain inflammatory mediators (18.6-40.6% prostaglandin E2 and 17.0-65.0% interleukin 1ß concentration). Cell death was reduced by 25.9, 37.5, and 41.0% after the administration of 1, 5, or 10 mg/kg/day. The administration of HT in rats with experimental diabetes thus had a neuroprotective effect.

Effects of hydroxytyrosol on cardiovascular biomarkers in experimental diabetes mellitus.

The aim of this study was to assess the influence of hydroxytyrosol (HT) on cardiovascular biomarkers and morphometric parameters of the arterial wall in streptozotocin-diabetic rats. Seven groups of rats (N=10 per group) were studied for 2 months: nondiabetic rats (NDR), diabetic rats treated with saline (DR) and DR treated with HT (0.5, 1, 2.5, 5 and 10 mg kg-1 day-1 p.o.). DR had higher platelet aggregation values, higher thromboxane B2, plasma lipid peroxidation, 3-nitrotyrosine, oxidized LDL (oxLDL), myeloperoxidase, vascular cell adhesion molecule 1 (VCAM-1) and interleukin-1ß (IL-1ß) concentrations, and lower aortic 6-keto-prostaglandin F1α and nitric oxide production than NDR. Aortic wall area and smooth muscle cell count were also higher in DR than in NDR. HT significantly reduced both oxidative and nitrosative stress, oxLDL concentration, VCAM-1 and inflammatory mediators, platelet aggregation and thromboxane B2 production. Morphometric values in the aortic wall were reduced to values near those in NDR. In conclusion, HT influenced the major biochemical processes leading to diabetic vasculopathy, and reduced cell proliferation in the vascular wall in this experimental model.

Evaluation of the Bioavailability and Metabolism of Nitroderivatives of Hydroxytyrosol Using Caco-2 and HepG2 Human Cell Models.

Considering that nitrocatechols present putative effects against Parkinson's disease, the absorption and metabolism of nitroderivatives of hydroxytyrosol (HT) were assessed using human cell model systems. The test compounds nitrohydroxytyrosol (NO2HT), nitrohydroxytyrosyl acetate (NO2HT-A), and ethyl nitrohydroxytyrosyl ether (NO2HT-E) were efficiently transferred across human Caco-2 cell monolayers as an intestinal barrier model, NO2HT-A and NO2HT-E being better (p < 0.05) absorbed (absorption rate (AR) = 1.4 ± 0.1 and 1.5 ± 0.2, respectively) than their precursor, NO2HT (AR = 1.1 ± 0.1). A significant amount of the absorbed compounds remained unconjugated (81, 70, and 33% for NO2HT, NO2HT-A, and NO2HT-E, respectively) after incubation in Caco-2 cells, being available for hepatic metabolism. Nitrocatechols were extensively taken up and metabolized by human hepatoma HepG2 cells as a model of the human liver. Both studies revealed extensive hydrolysis of NO2HT-A into NO2HT, whereas NO2HT-E was not hydrolyzed. Glucuronide (75-55%), methylglucuronide (25-33%), and methyl derivatives (0-12%) were the main nitrocatechol metabolites detected after metabolism in Caco-2 and HepG2 cells. In conclusion, NO2HT, NO2HT-A, and NO2HT-E show high in vitro bioavailability and are extensively metabolized by hepatic cells.

Differences in the Neuroprotective Effect of Orally Administered Virgin Olive Oil (Olea europaea) Polyphenols Tyrosol and Hydroxytyrosol in Rats.

The neuroprotective effect of virgin olive oil (VOO) polyphenols has been related to their antioxidant effect. The main objective was to analyze how tyrosol and hydroxytyrosol contribute to the antioxidant and neuroprotective effects of VOO in a model of hypoxia-reoxygenation in rat brain slices. Rats were treated per os (po) (10 or 20 mg/kg/day) with hydroxytyrosol ethyl ether (HTEE), tyrosol ethyl ether (TEE), or 3,4-di-o-methylidene-hydroxytyrosol ethyl ether (MHTEE), used as a negative control for antioxidant effects. Lipid peroxidation was inhibited with HTEE, TEE, and MHTEE (from 5.0 ± 1.5 to 2.6 ± 1.5, 4.5 ± 1.5, and 4.8 ± 1.5 nmol/mg protein, respectively). However, all three compounds had similar neuroprotective effects: from 2.8 ± 0.07 to 1.8 ± 0.02 arbitrary units for HTEE, 1.4 ± 0.09 arbitrary units for TEE, and 1.3 ± 0.2 arbitrary units for MHTEE. All three compounds inhibited 3-nitrotyrosine production (from 3.7 ± 0.3 to 1.2 ± 0.03 nmol/0.1 g tissue for HTEE, 1.0 ± 0.2 nmol/0.1 g tissue for TEE, and 1.3 ± 0.1 nmol/0.1 g tissue for MHTEE), prostaglandin E2 production (from 55.7 ± 2.2 to 46.4 ± 1.9 pg/0.1 g tissue for HTEE, 24.7 ± 1.3 pg/0.1 g tissue for TEE, and 27.6 ± 2.6 pg/0.1 g tissue for MHTEE), whereas only HTEE inhibited IL1ß production (from 35.7 ± 1.5 to 21.6 ± 0.8 pg/0.1 g tissue). Pearson correlation coefficients related neuroprotective effect with an antioxidant effect for HTEE (R = 0.72, p < 0.001), and inhibition of nitrosative stress (R = 0.78, 0.67, and 0.66 for HTEE, TEE, and MHTEE, respectively, p < 0.001) and inflammatory mediators (R = 0.72, 0.79, and 0.64 for HTEE, TEE, and MHTEE, respectively, p < 0.001) with all three compounds.

[Study of paracetamol levels in serum samples as predictive indicator of gastric emptying]. / EVALUACIÓN DEL TEST PARACETAMOL EN SUERO COMO INDICADOR PREDICTIVO DEL VACIADO GÁSTRICO.

INTRODUCTION: According to numerous studies, early initiation of nutrition in patients who have undergone surgery is essential. OBJETIVES: We analyzed the available techniques to assess gastric emptying in critically ill patients undergoing surgery, and holding the decision to introduce the type of feeding route. RESULTS: The measurement of gastric residual volume and auscultation are the standard tests used, but they have not shown great effectiveness. The acetaminophen absorption test seems to be a good predictive tool, that allows in 1 hour whether gastric emptying is right and thus, support the idea of continue with enteral nutrition, change to parenteral nutrition or evaluate the use of prokinetics drugs. DISCUSSION: Although there are studies whose final objective is the evaluation of the test as an indicator of tolerance of enteral nutrition, it is necessary to expand and standardize its use in order to include it in protocols for clinical practice.

Introducción: la iniciación temprana de la nutrición en pacientes intervenidos quirúrgicamente es fundamental. Objetivos: analizar las técnicas disponibles para evaluar el vaciado gástrico de los pacientes críticos sometidos a cirugía, y que apoyan la decisión de introducirles un tipo de alimentación u otro. Resultados: los test estándar son la medida del volumen residual gástrico y la auscultación, pero no han demostrado gran eficacia. El test de paracetamol parece una buena herramienta predictiva. Permitiría en una hora saber si el vaciado gástrico es adecuado y con ello seleccionar el tipo de nutrición más conveniente (enteral, parenteral) o evaluar el uso de procinéticos. Discusión: el test de paracetamol es una alternativa económica de alto valor predictivo. Existen estudios cuyo objetivo final es valorar el test como indicador de la tolerancia de la nutrición enteral, pero es necesario ampliar y estandarizar su uso para poder incluirlo en los protocolos de actuación hospitalarios.