Long-Term Effects of Microfiltered Seawater and Resistance Training with Elastic Bands on Hepatic Parameters, Inflammation, Oxidative Stress, and Blood Pressure of Older Women: A 32-Week, Double-Blinded, Randomized, Placebo-Controlled Trial.

The bulk of research on microfiltered seawater (SW) is based on its short-term effects. However, the long-term physiological adaptations to combining SW and resistance training (RT) are unknown. This study aimed to analyse the impact of an RT program using elastic bands combined with SW intake on hepatic biomarkers, inflammation, oxidative stress, and blood pressure in post-menopausal women. Ninety-three women voluntarily participated (age: 70 ± 6.26 years; body mass index: 22.05 ± 3.20 kg/m2; Up-and-Go Test: 6.66 ± 1.01 s). RT consisted of six exercises (32 weeks, 2 days/week). Nonsignificant differences were reported for hepatic biomarkers except for a reduction in glutamic-pyruvic transaminase (GPT) in both RT groups (RT + SW: p = 0.003, ES = 0.51; RT + Placebo: p = 0.012, ES = 0.36). Concerning oxidative stress, vitamin D increased significantly in RT + SW (p = 0.008, ES = 0.25). Regarding inflammation, interleukin 6 significantly decreased (p = 0.003, ES = 0.69) in RT + SW. Finally, systolic blood pressure significantly decreased in both RT groups (RT + placebo: p < 0.001, ES = 0.79; RT + SW: p < 0.001, ES = 0.71) as did diastolic blood pressure in both SW groups (RT + SW: p = 0.002, ES = 0.51; CON + SW: p = 0.028, ES = 0.50). Therefore, RT + SW or SW alone are safe strategies in the long term with no influences on hepatic and oxidative stress biomarkers. Additionally, SW in combination with RT positively influences vitamin D levels, inflammation, and blood pressure in older women.

Multicomponent and power training with elastic bands improve metabolic and inflammatory parameters, body composition and anthropometry, and physical function in older women with metabolic syndrome: A 20-week randomized, controlled trial.

PURPOSE: This study aimed to explore the effects of 20 weeks of multicomponent or power training with elastic bands (EBs) on metabolic and inflammatory blood parameters, body composition, anthropometry, and physical function in older women with metabolic syndrome (MS). METHODS: Ninety participants were randomly assigned to a multicomponent (MCG; n = 30), power (PG; n = 30), or a control group (CG; n = 30). The MCG performed balance, slow-speed strength, and aerobic training, twice per week. The PG completed a high-speed resistance training program twice per week, composed of three to four sets of ten repetitions of six overall body exercises at a perceived rating of effort for the first repetition of 3-4 on the OMNI-Resistance Exercise Scale EB. MS-related variables (glucose, triglycerides, and waist circumference) and cardiometabolic risk factors (high-density lipoprotein [HDL], glycosylated hemoglobin, total cholesterol, low-density lipoprotein cholesterol [LDL], C-reactive protein, and anthropometric profile) were assessed. Physical function was evaluated through balance, strength, and mobility tests. RESULTS: An analysis of variance revealed that both training groups similarly improved most glycemic and lipidic profile parameters (p ≤ 0.006; d ≥ 0.46), body composition and anthropometry (p < 0.001; d ≥ 0.41), and physical function (p ≤ 0.005; d ≥ 0.69). Opposed to the PG, the MCG improved balance (p < 0.001; d = 0.96) and decreased the inflammatory status by downregulating C-reactive protein (p = 0.003; d = 0.47). On the other hand, the PG exhibited improvements in handgrip strength (p = 0.006; d = 0.48), while the MCG did not. CONCLUSION: Therefore, multicomponent and power training with EBs are plausible strategies for improving the cardiometabolic health status and physical function in older women with MS.

Urinary levels of sirtuin-1 associated with disease activity in lupus nephritis.

Identifying new markers of disease flares in lupus nephritis (LN) that facilitate patient stratification and prognosis is important. Therefore, the aim of the present study was to analyze whether urinary SIRT1 expression was altered in LN and whether SIRT1 values in urine could be valuable biomarker of disease activity. In a cohort study, urinary pellets from 40 patients diagnosed with systemic lupus erythematosus (SLE) were analyzed. Clinical measures of lupus activity were assessed. The expression of SIRT1 was quantified by quantitative PCR (qRT-PCR) and immunoblot, then compared between patients with active lupus nephritis, in remission and healthy controls. Association with lupus activity and renal histological features was also analyzed. A significant increase in SIRT1 mRNA levels in patients with active LN was observed compared with those in remission (P=0.02) or healthy controls (P=0.009). In addition, SIRT-1 protein levels were also augmented in LN group than remission (P=0.029) and controls (P=0.001). A strong association was found between SIRT1 expression with anti-dsDNA in SLE and in patients with LN. In addition, histological features in LN biopsies were related with SIRT1, increasing its expression in proliferative forms. Finally, SIRT1 expression values showed a strong discriminatory power of renal injury in SLE. Our study demonstrated an altered urinary expression of SIRT1 and a strong association with disease activity in LN patients, being a valuable marker of renal injury. These results showed the role of the SIRT1 pathway in the SLE pathogenesis.

Effects of the Ser326Cys Polymorphism in the DNA Repair OGG1 Gene on Cancer, Cardiovascular, and All-Cause Mortality in the PREDIMED Study: Modulation by Diet.

BACKGROUND: Oxidatively induced DNA damage, an important factor in cancer etiology, is repaired by oxyguanine glycosylase 1 (OGG1). The lower repair capacity genotype (homozygote Cys326Cys) in the OGG1-rs1052133 (Ser326Cys) polymorphism has been associated with cancer risk. However, no information is available in relation to cancer mortality, other causes of death, and modulation by diet. OBJECTIVE: Our aim was to evaluate the association of the OGG1-rs1052133 with total, cancer, and cardiovascular disease (CVD) mortality and to analyze its modulation by the Mediterranean diet, focusing especially on total vegetable intake as one of the main characteristics of this diet. DESIGN: Secondary analysis in the PREDIMED (Prevención con Dieta Mediterránea) trial is a randomized, controlled trial conducted in Spain from 2003 to 2010. PARTICIPANTS/SETTING: Study participants (n=7,170) were at high risk for CVD and were aged 55 to 80 years. INTERVENTION: Participants were randomly allocated to two groups with a Mediterranean diet intervention or a control diet. Vegetable intake was measured at baseline. MAIN OUTCOME MEASURES: Main outcomes were all-cause, cancer, and CVD mortality after a median follow-up of 4.8 years. STATISTICAL ANALYSES: Multivariable-adjusted Cox regression models were fitted. RESULTS: Three hundred eighteen deaths were detected (cancer, n=127; CVD, n=81; and other, n=110). Cys326Cys individuals (prevalence 4.2%) presented higher total mortality rates than Ser326-carriers (P=0.009). The multivariable-adjusted hazard ratio for Cys326Cys vs Ser326-carriers was 1.69 (95% CI 1.09 to 2.62; P=0.018). This association was greater for CVD mortality (P=0.001). No relationship was detected for cancer mortality in the whole population (hazard ratio 1.07; 95% CI 0.47 to 2.45; P=0.867), but a significant age interaction (P=0.048) was observed, as Cys326Cys was associated with cancer mortality in participants <66.5 years (P=0.029). Recessive effects limited our ability to investigate Cys326Cys×diet interactions for cancer mortality. No statistically significant interactions for total or CVD mortality were found for the Mediterranean diet intervention. However, significant protective interactions for CVD mortality were found for vegetable intake (hazard ratio interaction per standard deviation 0.42; 95% CI 0.18 to 0.98; P=0.046). CONCLUSIONS: In this population, the Cys326Cys-OGG1 genotype was associated with all-cause mortality, mainly CVD instead of cancer mortality. Additional studies are needed to provide further evidence on its dietary modulation.

The Effect of Moderate- Versus High-Intensity Resistance Training on Systemic Redox State and DNA Damage in Healthy Older Women.

This study investigated effects of a 16-week progressive resistance training program (RTP) with elastic bands at two different intensities on systemic redox state, DNA damage, and physical function in healthy older women. METHODS: Participants were randomly assigned to the high-intensity group (HIGH; n = 39), moderate-intensity group (MOD; n = 31), or control group (CG; n = 23). The exercise groups performed an RTP twice a week with three to four sets of 6 (HIGH) or 15 (MOD) repetitions of six overall body exercises at a perceived exertion rate of 8-9 on the OMNI-Resistance Exercise Scale for use with elastic bands. Thiol redox state was determined by reduced glutathione (GSH), oxidized glutathione (GSSG), and GSSG/GSH in blood mononuclear cells. Degree of DNA damage was assessed by presence of the oxidized DNA base molecule 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-OHdG) in urine. Physical function monitoring was based on the arm curl, chair stand, up and go, and 6-min walk tests. RESULTS: The HIGH group showed a significant increase in 8-OHdG (+71.07%, effect size [ES] = 1.12) and a significant decrease in GSH (-10.91, ES = -0.69), while the MOD group showed a significant decrease in 8-OHdG levels (-25.66%, ES = -0.69) with no changes in thiol redox state. GSH levels differed significantly between the HIGH and CG groups posttest. The exercise groups showed significant improvements in physical function with no differences between groups. CONCLUSION: RTP at a moderate rather than high intensity may be a better strategy to reduce DNA damage in healthy older women while also increasing independence.

PAI-1 levels are related to insulin resistance and carotid atherosclerosis in subjects with familial combined hyperlipidemia.

Familial combined hyperlipidemia (FCH) is a primary atherogenic dyslipidemia with insulin resistance and increased cardiovascular risk. Plasminogen activator inhibitor type 1 (PAI-1) and myeloperoxidase (MPO) activity are associated with proinflammatory and atherothrombotic risk. Our aim was to study the role played by PAI-1 and MPO activity in the carotid atherosclerosis prevalence in FCH subjects. 36 FCH unrelated subjects (17 women) were matched by age and body weight with 36 healthy normolipidemic subjects (19 female). Blood lipids, glucose, insulin, insulin resistance (homeostasis model assessment (HOMA)), MPO, and PAI-1 were determined in both groups. Carotid intima media thickness (IMT) was measured by the same investigator by standardized protocol. No differences in age, body mass index (BMI) or waist circumference were observed between the two groups. HOMA and PAI-1 values were higher in the FCH group, reaching statistical significance in those subjects with insulin resistance. In addition, PAI-1 values correlated significantly with metabolic syndrome components and carotid IMT. It is known that the elevated cardiovascular risk that characterizes FCH is frequently associated with insulin resistance. We have detected that two known proinflammatory and proatherothrombotic factors (MPO and PAI-1) are significantly elevated in FCH subjects with insulin resistance. These results could partly explain the high cardiovascular risk present in FCH subjects.

Oxidative imbalance in low/intermediate-1-risk myelodysplastic syndrome patients: The influence of iron overload.

OBJECTIVE: To assess the generation of reactive oxygen species (ROS) and the involvement of the main antioxidant pathways in low/intermediate-1-risk myelodysplastic syndromes (MDS) with iron overload (IOL). METHODS: We examined the levels of superoxide anion (O2-), hydrogen peroxide (H2O2), antioxidants (glutathione, GSH; superoxide dismutase, SOD; catalase, CAT; and glutathione peroxidase, GPx), mitochondrial membrane potential (ΔΨm), and by-products of oxidative damage (8-isoprostanes and 8-oxo-7,8-dihydro-2'-deoxyguanosine, 8-oxo-dG) in 42 MDS patients (28 without IOL at diagnosis, and 14 who developed IOL) and 20 healthy subjects. RESULTS: Patients with IOL showed higher O2- levels (39.4 MFI) than normal controls (22.7 MFI, p=0.0356) and patients at diagnosis (19.4 MFI, p=0.0049). Antioxidant systems, except SOD activity, exhibited significant changes in IOL patients with respect to controls (CAT: 7.1 vs 2.7nmol/ml/min, p=0.0023; GPx: 50.9 vs 76.4nmol/ml/min, p=0.0291; GSH: 50.2 vs 24.1 MFI, p=0.0060). Furthermore, mitochondrial dysfunction was only detected in IOL cases compared to controls (ΔΨm: 3.6 vs 6.4 MFI, p=0.0225). Finally, increased levels of 8-oxo-dG were detected in both groups of patients. CONCLUSION: Oxidative stress is an important but non-static phenomenon in MDS disease, whose status is influenced by, among other factors, the presence of injurious iron.

One-year follow-up of clinical, metabolic and oxidative stress profile of morbid obese patients after laparoscopic sleeve gastrectomy. 8-oxo-dG as a clinical marker.

Obesity has grown worldwide over the last few decades. In its different degrees, obesity is accompanied by many clinical and biochemical alterations reflecting the pathological condition of various body tissues. Among the mechanisms underlying the pathogenesis of obesity and associated complications, oxidative stress (OS) may be playing an important role. In the present study, we have characterized at systemic level the degree of OS status in a group of morbid obese patients (BMI>40kg/m2) at basal sate and its modulation during one year after bariatric surgery using the laparoscopic sleeve gastrectomy (LSG) technique. As compared with normal weight subjects matched in age, peripheral blood mononuclear cells (PBMc) of obese patients present a significant reduction of the antioxidant enzyme activities superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) as well as a significant increase of the oxidized/reduced glutathione ratio (GSSG/GSH) in these cells. Lipid peroxidation is significantly increased in the patient group as shown by the increased levels of malondialdehyde (MDA) in PBMc and the amount of F2-Isoprostanes (F2-IsoPs) released in urine. In addition, the DNA damage product 8-oxo-7,8-2'-deoxyguanosine (8-oxo-dG) was also observed to be increased in serum and urine of morbid obese patients as compared with the control group. After LSG, an improvement of their ponderal and metabolic profile was accompanied by a progressive recovery of antioxidant enzyme activities and the decline of oxidative byproducts both in PBMc and biological fluids. The observed changes of urinary 8-oxo-dG levels correlate positively with its serum concentration, the lipid peroxidation products MDA and F2-IsoPs, triglycerides, glucose, insulin, HOMA index and body weight and negatively with the percentage of weight and BMI loss and antioxidant activities. We conclude that the analysis of urinary 8-oxo-dG could be validated as a useful marker for the monitoring of ponderal and metabolic status of morbid obese patients.

Effect of olive oil phenolic compounds on the expression of blood pressure-related genes in healthy individuals.

PURPOSE: To investigate whether the ingestion of olive oil having different phenolic contents influences the expression of blood pressure-related genes, involved in the renin-angiotensin-aldosterone system, in healthy humans. METHODS: A randomized, double-blind, crossover human trial with 18 healthy subjects, who ingested 25 mL/day of olive oils (1) high (366 mg/kg, HPC) and (2) low (2.7 mg/kg, LPC) in phenolic compounds for 3 weeks, preceded by 2-week washout periods. Determination of selected blood pressure-related gene expression in peripheral blood mononuclear cells (PBMNC) by qPCR, blood pressure and systemic biomarkers. RESULTS: HPC decreased systolic blood pressure compared to pre-intervention values and to LPC, and maintained diastolic blood pressure values compared to LPC. HPC decreased ACE and NR1H2 gene expressions compared with pre-intervention values, and IL8RA gene expression compared with LPC. CONCLUSIONS: The introduction to the diet of an extra-virgin olive oil rich in phenolic compounds modulates the expression of some of the genes related to the renin-angiotensin-aldosterone system. These changes could underlie the decrease in systolic blood pressure observed.

Frying oils with high natural or added antioxidants content, which protect against postprandial oxidative stress, also protect against DNA oxidation damage.

PURPOSE: Using sunflower oil as frying oil increases postprandial oxidative stress, which is considered the main endogenous source of DNA oxidative damage. We aimed to test whether the protective effect of virgin olive oil and oil models with added antioxidants against postprandial oxidative stress may also protect against DNA oxidative damage. METHODS: Twenty obese people received four breakfasts following a randomized crossover design consisting of different oils [virgin olive oil (VOO), sunflower oil (SFO), and a mixed seed oil (SFO/canola oil) with added dimethylpolysiloxane (SOX) or natural antioxidants from olives (SOP)], which were subjected to 20 heating cycles. RESULTS: We observed the postprandial increase in the mRNA levels of p53, OGG1, POLB, and GADD45b after the intake of the breakfast prepared with SFO and SOX, and an increase in the expression of MDM2, APEX1, and XPC after the intake of the breakfast prepared with SFO, whereas no significant changes at the postprandial state were observed after the intake of the other breakfasts (all p values <0.05). We observed lower 8-OHdG postprandial levels after the intake of the breakfast prepared with VOO and SOP than after the intake of the breakfast prepared with SFO and SOX (all p values <0.05). CONCLUSIONS: Our results support the beneficial effect on DNA oxidation damage of virgin olive oil and the oil models with added antioxidants, as compared to the detrimental use of sunflower oil, which induces p53-dependent DNA repair pathway activation.

Increased thioredoxin levels are related to insulin resistance in familial combined hyperlipidaemia.

BACKGROUND: Thioredoxins (TRX) are major cellular protein disulphide reductases that are critical for redox regulation. Oxidative stress and inflammation play promoting roles in the genesis and progression of atherosclerosis, but until now scarce data are available considering the influence of TRX activity in familial combined hyperlipidaemia (FCH). Since FCH is associated with high risk of cardiovascular disease, the objective of the present study was to assess oxidative stress status in FCH patients, and evaluate the influence of insulin resistance (IR). MATERIALS AND METHODS: A cohort of 35 control subjects and 35 non-related FCH patients were included, all of them nondiabetic, normotensive and nonsmokers. We measured lipid profile, glucose and insulin levels in plasma, and markers of oxidative stress and inflammation such as oxidized glutathione (GSSG), reduced glutathione (GSH) and TRX. RESULTS: Familial combined hyperlipidaemia subjects showed significantly higher levels of GSSG, GSSG/GSH ratio and TRX than controls. In addition, FCH individuals with IR showed the worst profile of oxidative stress status compared to controls and FCH patients without IR (P < 0·01). TRX levels correlated with higher insulin resistance. CONCLUSION: Familial combined hyperlipidaemia patients showed increased TRX levels. TRX was positively correlated with IR. These data could partially explain the increased risk of cardiovascular events in primary dyslipidemic patients.

Salivary and serum interleukin-6 levels in proliferative verrucous leukoplakia.

BACKGROUND: Cytokines and chemokines have been analysed in patients with oral squamous cell carcinoma and potentially malignant disorders. We selected interleukin-6 (IL-6) because it is a multifunctional interleukin reported to be altered in potentially malignant oral disorders and in malignant lesions. To date, this has not been evaluated or tested in proliferative verrucous leukoplakia (PVL), however. OBJECTIVES: This study aimed to analyse the differences in serum and saliva IL-6 levels among patients with PVL, oral squamous cell carcinoma (OSCC) and healthy controls and to examine the relationship between salivary IL-6 levels and the extent of the verrucous area. METHODS: Using an enzyme-linked immunosorbent assay, we determined the serum and saliva IL-6 levels in three groups: 20 patients with PVL, 20 with OSCC and 20 healthy controls. RESULTS: There were significant (p < 0.01) differences in the serum and saliva IL-6 levels among the three groups and among the three grades of extent of the verrucous areas (p = 0.01). In the OSCC group, there was a significant difference in the saliva IL-6 levels between patients with and without lymph node metastasis at diagnosis (p = 0.02). CONCLUSIONS: We found that patients with OSCC had the highest salivary and serum IL-6 levels, while PVL had lower values than OSCC, but higher than the controls, and these altered levels were associated with the extent of the verrucous areas. CLINICAL RELEVANCE: Salivary and plasma IL-6 are altered in patients with PVL, with more extensive verrucous areas being associated to the highest IL-6 levels. This could be a significant tool for monitoring patients with PVL, their progression to more advances stages and their recurrences.

Pterostilbene Decreases the Antioxidant Defenses of Aggressive Cancer Cells In Vivo: A Physiological Glucocorticoids- and Nrf2-Dependent Mechanism.

AIMS: Polyphenolic phytochemicals have anticancer properties. However, in mechanistic studies, lack of correlation with the bioavailable concentrations is a critical issue. Some reports had suggested that these molecules downregulate the stress response, which may affect growth and the antioxidant protection of malignant cells. Initially, we studied this potential underlying mechanism using different human melanomas (with genetic backgrounds correlating with most melanomas), growing in nude mice as xenografts, and pterostilbene (Pter, a natural dimethoxylated analog of resveratrol). RESULTS: Intravenous administration of Pter decreased human melanoma growth in vivo. However, Pter, at levels measured within the tumors, did not affect melanoma growth in vitro. Pter inhibited pituitary production of the adrenocorticotropin hormone (ACTH), decreased plasma levels of corticosterone, and thereby downregulated the glucocorticoid receptor- and nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-dependent antioxidant defense system in growing melanomas. Exogenous corticosterone or genetically induced Nrf2 overexpression in melanoma cells prevented the inhibition of tumor growth and decreased antioxidant defenses in these malignant cells. These effects and mechanisms were also found in mice bearing different human pancreatic cancers. Glutathione depletion (selected as an antimelanoma strategy) facilitated the complete elimination by chemotherapy of melanoma cells isolated from mice treated with Pter. INNOVATION: Although bioavailability-related limitations may preclude direct anticancer effects in vivo, natural polyphenols may also interfere with the growth and defense of cancer cells by downregulating the pituitary gland-dependent ACTH synthesis. CONCLUSIONS: Pter downregulates glucocorticoid production, thus decreasing the glucocorticoid receptor and Nrf2-dependent signaling/transcription and the antioxidant protection of melanoma and pancreatic cancer cells. Antioxid. Redox Signal. 24, 974-990.

Klotho urinario determinado por ELISA como biomarcador precoz de fracaso renal agudo en pacientes sometidos a cirugía cardiaca o angiografía coronaria / ELISA-measured urinary Klotho as an early biomarker of acute kidney failure in patients undergoing heart surgery or coronary angiography

Introducción y objetivos: El fracaso renal agudo (FRA) es una complicación frecuente tras la cirugía cardiaca y las intervenciones percutáneas coronarias cuya aparición empeora el pronóstico de manera marcada. En los últimos años se han identificado nuevos biomarcadores precoces de FRA, pero aún quedan muchos aspectos importantes por resolver. Klotho es una proteína pleiotrópica que actúa como un factor paracrino y endocrino en múltiples órganos. En diversos modelos animales de FRA se ha demostrado niveles disminuidos de Klotho renal. No se ha publicado ningún estudio en el que se haya probado Klotho como marcador precoz de FRA en humanos. El objetivo de este trabajo es investigar la utilidad de la determinación de Klotho en orina para el diagnóstico precoz del FRA en pacientes con síndrome coronario agudo ofallo cardiaco sometidos a cirugía cardiaca o angiografía coronaria. Métodos: Se midió Klotho urinario 12 horas tras la intervención en 60 pacientes ingresados en la unidad de cuidados intensivos por síndrome coronario agudo o fallo cardiaco secundarios a enfermedad coronaria o valvular y a los que se realizó angiografía coronaria (30 pacientes)o cirugía cardiaca de recambio valvular o bypass (30 pacientes). El criterio de valoración primario fue la aparición de FRA según la clasificación RIFLE. Los niveles de Klotho humano se midieron utilizando un ensayo ELISA. Resultados: No encontramos diferencias en los niveles de Klotho en orina entre los pacientes que desarrollaron FRA y aquellos que no. Además, no había correlación significativa entre niveles de klotho en orina y presencia de FRA. Conclusión: Klotho urinario medido por ELISA no parece ser un buen candidato para ser usado como biomarcador precoz de FRA (AU)

Introduction and objectives: Acute kidney injury (AKI) is a common complication after cardiacsurgery and percutaneous coronary interventions that markedly worsens prognosis. In the last years new early biomarkers for AKI have been identified, but many important aspects still remain to be solved. Klotho is a pleiotropic protein that acts as a paracrine and endocrine hormonal factor in multiple organs. Renal Klotho deficiency has been shown in several AKI animal models. No study has been published in which Klotho was tested in humans as an early biomarker of AKI. The aim of this study was to assess the usefulness of urinary determination of Klotho for the early detection of AKI in patients with acute coronary syndrome or heart failure undergoing cardiac surgery or coronary angiography. Methods: Urinary Klotho was measured 12 hours after intervention in 60 patients admitted to the Intensive Care Unit with acute coronary syndrome or heart failure due to coronary or valvular pathologies, who underwent coronary angiography (30 patients), or cardiac bypass surgery or heart valve replacement (30 patients). The endpoint used for evaluating our patients was the appearance of AKI, in keeping with the RIFLE classification system. Human Klotho levels were measured using an ELISA assay. Results: We found no differences in urinary Klotho levels between patients with AKI and those who did not develop AKI. Moreover, there was no significant correlation between urinary Klotho levels and AKI development. Conclusions: Urinary Klotho measured by ELISA does not seem to be a good candidate to be used as an early biomarker of AKI (AU)

Oxidative stress is associated with an increased antioxidant defense in elderly subjects: a multilevel approach.

BACKGROUND: Studies of associations between plasma GSH-Px activity and cardiovascular risk factors have been done in humans, and contradictory results have been reported. The aim of our study was to assess the association between the scavenger antioxidant enzyme glutathione peroxidase (GSH-Px) activity in plasma and the presence of novel and classical cardiovascular risk factors in elderly patients. METHODS: We performed a cross-sectional study with baseline data from a subsample of the PREDIMED (PREvención con DIeta MEDiterránea) study in Spain. Participants were 1,060 asymptomatic subjects at high risk for cardiovascular disease (CVD), aged 55 to 80, selected from 8 primary health care centers (PHCCs). We assessed classical CVD risk factors, plasma oxidized low-density lipoproteins (ox-LDL), and glutathione peroxidase (GSH-Px) using multilevel statistical procedures. RESULTS: Mean GSH-Px value was 612 U/L (SE: 12 U/L), with variation between PHCCs ranging from 549 to 674 U/L (Variance =  013.5; P<0.001). Between-participants variability within a PHCC accounted for 89% of the total variation. Both glucose and oxidized LDL were positively associated with GSH-Px activity after adjustment for possible confounder variables (P = 0.03 and P = 0.01, respectively). CONCLUSION: In a population at high cardiovascular risk, a positive linear association was observed between plasma GSH-Px activity and both glucose and ox-LDL levels. The high GSH-Px activity observed when an oxidative stress situation occurred, such as hyperglycemia and lipid oxidative damage, could be interpreted as a healthy defensive response against oxidative injury in our cardiovascular risk population.

MicroRNA-410 regulated lipoprotein lipase variant rs13702 is associated with stroke incidence and modulated by diet in the randomized controlled PREDIMED trial.

BACKGROUND: MicroRNAs have emerged as important epigenetic regulators in cardiovascular diseases (CVDs). Using an observational meta-analysis design, we previously characterized a gain-of-function microRNA-410 target site polymorphism (rs13702T>C) in the 3'untranslated region of the lipoprotein lipase (LPL) gene. The C allele was associated with lower triglycerides, and this association was modulated by fat intake. OBJECTIVES: We aimed to extend our findings by assessing the interaction between the rs13702 polymorphism and fat intake on triglycerides at baseline and longitudinally by using a dietary intervention design. We also examined as a primary outcome the association of this variant with CVD incidence and its modulation by the Mediterranean diet (MedDiet). DESIGN: We studied 7187 participants in the PREDIMED (Prevención con Dieta Mediterránea) randomized trial that tested a MedDiet intervention compared with a control diet, with a median 4.8-y follow-up. LPL polymorphisms and triglycerides were determined and CVD assessed. Gene-diet interactions for triglycerides were analyzed at baseline (n = 6880) and after a 3-y intervention (n = 4131). Oxidative stress parameters were investigated in a subsample. RESULTS: The rs13702T>C polymorphism was strongly associated with lower triglycerides in C allele carriers and interacted synergistically with dietary monounsaturated (P = 0.038) and unsaturated fat intake (P = 0.037), decreasing triglycerides at baseline. By 3 y, we observed a gene-diet interaction (P = 0.025) in which the C allele was associated with a greater reduction in triglycerides after intervention with MedDiet, high in unsaturated fat. Although the polymorphism was associated with lower stroke risk (HR: 0.74; 95% CI: 0.57, 0.97; P = 0.029 per C allele), this association reached statistical significance only in the MedDiet intervention (HR: 0.58; 95% CI: 0.37, 0.91; P = 0.019 in C compared with TT carriers), not in the control group (HR: 0.94; 95% CI: 0.55, 1.59; P = 0.805). CONCLUSION: We report a novel association between a microRNA target site variant and stroke incidence, which is modulated by diet in terms of decreasing triglycerides and possibly stroke risk in rs13702 C allele carriers after a high-unsaturated fat MedDiet intervention.

Increased oxidative damage associated with unfavorable cytogenetic subgroups in chronic lymphocytic leukemia.

Oxidative stress contributes to genomic instability in chronic lymphocytic leukemia (CLL), but its relationship with the acquisition of specific chromosomal abnormalities is unknown. We recruited 55 untreated CLL patients and assessed 8-oxo-2'-deoxyguanosine (8-oxo-dG), glutathione, and malondialdehyde (MDA) levels, and we compared them among the cytogenetic subgroups established using fluorescence in situ hybridization (FISH). Significant increases in 8-oxo-dG and/or MDA were observed in patients with unfavorable cytogenetic aberrations (17p and 11q deletions) compared to the 13q deletion group. TP53 deletion patients exhibited a diminished DNA repair efficiency. Finally, cases with normal FISH also showed enhanced 8-oxo-dG, which could result in adverse outcomes.