A new 8-oxo-7,8-2'deoxyguanosine nanoporous anodic alumina aptasensor for colorectal cancer diagnosis in blood and urine.

Many important human diseases, and especially cancer, have been related to the overproduction of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG). This molecule is a product of oxidative stress processes over nucleophilic bases in DNA. In this work, an aptasensor for the rapid, selective and accurate detection of this oncomarker is presented. The aptasensor consists of a nanoporous anodic alumina material loaded with a dye and is functionalized with an aptamer-based "molecular gate". In the presence of target 8-oxo-dG, the capping aptamer displaces from the surface due to the high affinity of the analyte with the capping aptamer, thus inducing delivery of the preloaded fluorescent dye. In contrast, in the absence of 8-oxo-dG, a poor payload delivery is accomplished. This aptamer-based nanodevice has great sensitivity for 8-oxo-dG, resulting in a LOD of 1 nM and a detection time of ca. 60 min. Moreover, the aptasensor is able to accurately detect 8-oxo-dG in unmodified urine and serum without pre-concentration treatments. This diagnostic tool is validated in a set of 38 urine and serum samples from patients diagnosed of colorectal cancer and control patients. These samples are also analyzed using a standardized and specific ELISA kit. The aptasensor displays excellent sensitivity (95.83/100%) and specificity (80/100%) for 8-oxo-dG detection in serum and urine samples, respectively. Our results may serve as a basis for the development of generalized fluorogenic diagnostic platforms for the easy diagnosis of cancer in biofluids as well as for monitoring therapeutic treatments and detection of relapses without the use of expensive equipment or trained personnel.

Chronic consumption of an inositol-enriched carob extract improves postprandial glycaemia and insulin sensitivity in healthy subjects: A randomized controlled trial.

BACKGROUND & AIMS: Inositols are thought to be mediators of the insulin signalling pathway. We assessed the effects of inositols on glycaemic control in fasting and postprandial states and evaluated lipoprotein profile and LDL particle size in healthy population. METHODS: A 12-week double-blind clinical trial was performed with forty healthy subjects administered either an inositol-enriched beverage (IEB) -containing 2.23 g of inositols in 250 ml- or a sucrose-sweetened beverage (SB) twice a day. Anthropometric measurements, fasting glucose levels, insulin and HOMA-IR index, lipoprotein profile and postprandial glucose concentrations (measured using the continuous glucose monitoring system (CGMS)) were recorded throughout the intervention period. RESULTS: Following the 12-week trial subjects receiving the IEB exhibited a significant decrease in insulin, HOMA-IR and Apo B and an increase in LDL particle size, whereas the SB group showed increases in BMI and fasting glucose concentration. Analysis of postprandial glucose levels at breakfast, lunch and dinner revealed a mean reduction of glucose of ≈14% and a significant reduction in the area under the curve at 24 h after consumption of the IEB. CONCLUSIONS: Our results show that chronic IEB supplementation induces a significant improvement in carbohydrated metabolism parameters in healthy subjects.

A single acute dose of pinitol from a naturally-occurring food ingredient decreases hyperglycaemia and circulating insulin levels in healthy subjects.

A limited amount of research suggests that oral ingestion of pinitol (3-O-methyl-d-chiro-inositol) positively influences glucose tolerance in humans. This study assessed the effects of different doses of pinitol supplementation on glucose tolerance, insulin sensitivity and plasma pinitol concentrations. Thirty healthy subjects underwent two one-day trials in which they consumed a nutritive beverage (Fruit Up®) containing 2.5, 4.0 or 6.0g of pinitol and a corresponding placebo equivalent in both energy and carbohydrates. Blood samples were collected frequently over the 240-min test period. The pinitol-enriched beverage reduced serum glucose and insulin at 45 and 60min, but only at a dose of 6.0g. Plasma pinitol concentrations, maximum concentration and AUC increased according to the dose administered. The results show that a single dose of pinitol from a naturally-occurring food ingredient at the highest dose administered acutely influences indices of whole-body glucose tolerance and insulin sensitivity in healthy subjects.

A review on the role of phytosterols: new insights into cardiovascular risk.

Phytosterols, which are structurally related to cholesterol, are found in all plant foods with highest concentration occurring in vegetable oils and nuts. Phytosterols are known to reduce serum low-density lipoprotein cholesterol level without changing high-density lipoprotein cholesterol or triglyceride levels. Daily consumption of phytosterols-enriched foods is widely used as a therapeutic option to lower plasma cholesterol and atherosclerotic disease risk. The cholesterol-lowering action of phytosterols is thought to occur, at least in part, through competitive replacement of dietary and biliary cholesterol in mixed micelles, which undermines the absorption of cholesterol. The aim of this review is to provide a general overview of available evidence regarding the effects of phytosterols on cholesterol metabolism and addressing issues related to efficacy as dose, length, frequency of consumption, type of phytosterol (sterols versus stanols) or food matrix. Furthermore, we will explore the factors that influence the response of individuals to phytosterol therapy and evaluate their safety and the possibility that elevated plasma phytosterol concentrations contribute to the development of premature coronary artery disease.

Low intestinal cholesterol absorption is associated with a reduced efficacy of phytosterol esters as hypolipemic agents in patients with metabolic syndrome.

BACKGROUND & AIMS: Phytosterols (PS) lower LDLc, but their effect on metabolic syndrome (MetS) remains unknown. We evaluated whether low-fat milk enriched with PS improves cardiovascular risk factors in these patients. METHODS: A randomised parallel trial employing 24 moderate-hypercholesterolaemic MetS patients and consisting of two 3-month intervention phases. After a 3-month healthy diet, patients were divided into two intervention groups: diet (n = 10) and diet + PS (n = 14) (2 g/day). A control group of 24 moderate-hypercholesterolaemic patients without MetS (matched in age and BMI) underwent the same procedure. RESULTS: Neither dietary intervention nor enrichment of PS induced any improvement in the serum lipoprotein profile of MetS patients. By contrast, in the non-MetS population, a healthy diet effectively reduced TC, LDLc, non-HDLc and Apo B-100, with further decreases in TC (6.9%), LDLc (10.5%), non-HDLc (10.3%), Apo B-100 (6.2%) and Apo B-100/ApoA-I ratio (11.6%) being observed when PS were administered. No differences in LDL diameter, hsCRP or homocysteine were detected in any of the groups after consuming PS. This supplementation produced a significant increase in PS levels only in the non-MetS population. CONCLUSIONS: PS therapy appears to be of little value to MetS patients, likely due to its reduced intestinal cholesterol absorption. The efficacy of PS as hypocholesterolaemic agents is thus limited.

[Low doses of megestrol acetate increase weight and improve nutrition status in patients with severe chronic obstructive pulmonary disease and weight loss]. / Dosis bajas de acetato de megestrol aumentan el peso y mejoran la nutrición de los pacientes con enfermedad pulmonar obstructiva crónica grave y pérdida de peso.

BACKGROUND AND OBJECTIVE: Weight loss in patients with severe chronic obstructive pulmonary disease (COPD) is a prognostic bad factor. The objective of this study is to analyze the effectively of megestrol acetate (MA) to increase appetite of these patients. PATIENTS AND METHODS: Randomized double blind placebo controlled trial to study the effect of 160 mg/bid of MA, for 8 weeks, on nutritional, functional, analytical and quality of life parameters, in 38 patients with severe COPD and body mass index (BMI) < 21 kg/m(2), or between 21-25 with involuntary weight loss of 5% in the last 3 months. RESULTS: At 8 weeks, in the MA group the body weight increased (2.3 kg) with respect to the control group (0.1 kg) (p<0.04). MA improved significantly the triceps skin-fold thickness (p < 0.04), prealbumin (p<0.004), lymphocytes (p<0.0006), C3 (p<0.04), PCO(2) (p<0.007) and bicarbonate levels (p<0.008). MA did not increase the MRC and SGRQ scales, the distance of 6 MWT nor BODE index. The IL-6 and TNF alpha levels were not modified in the MA group, but leptin did increase (p<0.043). MA improved the sense of wellbeing (p<0.02) and the appetite (p<0.008), compared to the control group. Adverse effects were similar in both groups. CONCLUSIONS: MA safely increases the body weight and the appetite in severe COPD patients with weight loss. MA improves blood gases and nutritional parameters and the sense of wellbeing, but it does not improve the respiratory muscular function or exercise tolerance.

Effects of phytosterol ester-enriched low-fat milk on serum lipoprotein profile in mildly hypercholesterolaemic patients are not related to dietary cholesterol or saturated fat intake.

Phytosterols (PS) are recommended to reduce LDL-cholesterol. However, the influence of cholesterol and fat intake on the lipid-lowering effect of PS in mildly hypercholesterolaemia is unclear. Thus, the aim of the present study was to evaluate whether the efficacy of PS is related to the composition of saturated fat and dietary cholesterol intake. Additionally, serum carotenoid content was analysed to evaluate to what extent it was undermined by PS. This was a 3-month randomised, parallel trial with a three-arm design. Patients were divided into three groups: healthy diet (n 24), healthy diet+PS (n 31) and free diet+PS (n 29), receiving 2 g/d of PS. Healthy and free diets were characterised by a daily ingestion of 6.8 % of saturated fat and 194.4 mg of cholesterol and 12.7 % of saturated fat and 268.1 mg of cholesterol, respectively. After PS therapy, patients receiving the healthy diet+PS or a free diet+PS exhibited a similar reduction in total cholesterol (6.7 and 5.5 %), LDL-cholesterol (9.6 and 7.0 %), non-HDL-cholesterol (12.2 and 8.9 %) and apo B-100/apo A-I ratio (11.5 and 11.6 %), respectively. In patients following the healthy diet, (ß-carotene concentration rose by 26.9 %, whereas the ß-carotene and lycopene levels dropped by 21.0 and 22.8 % in the group receiving the free diet+PS, respectively. No change was observed in carotenoid levels in healthy diet+PS group. In conclusion, the efficacy of PS in relation to lipoprotein profile is not influenced by saturated fat or dietary cholesterol intake, which confirms the positive effect of healthy diet therapy in improving the negative effects that PS exert on carotenoid levels.

Evaluation of cardiovascular risk and oxidative stress parameters in hypercholesterolemic subjects on a standard healthy diet including low-fat milk enriched with plant sterols.

A healthy diet and plant sterols (PS) are recommended for reducing low-density lipoprotein (LDL) cholesterol and, subsequently, the risk of premature cardiovascular disease. PS mediate a decrease in fat-soluble vitamin concentration, which can lead to a general impairment of antioxidative defenses and an increase in oxidative stress. Thus, we evaluated the effects of a healthy diet, including PS-enriched low-fat milk, on cardiovascular risk and oxidative stress parameters in hypercholesterolemic subjects. This was a randomized parallel trial employing 40 subjects and consisting of two 3-month intervention phases. After 3 months on a standard healthy diet, subjects were divided into two intervention groups: a diet group and a diet+PS group (2 g/day). Lipid profile, apolipoproteins, high-sensitivity C-reactive protein and oxidative stress parameters were analyzed. Diet significantly reduced total and LDL cholesterol (4.0% and 4.7%, respectively), produced an increase in the level of beta-carotene (23%) and improved the antioxidant capacity of LDL cholesterol particles (4.6%). PS induced a significant decrease in total cholesterol (6.4%), LDL (9.9%) and the apolipoprotein B100/apolipoprotein A1 ratio (4.9%), but led to a decrease in cryptoxanthin level (29%) without any change being observed in the antioxidant capacity of LDL cholesterol particles, total antioxidant status or lipid peroxidation. After 3 months, we observed the positive effect of including a PS supplement in dietary measures, as the lipoprotein-mediated risk of cardiovascular disease was reduced. Despite a decrease in the concentration of cryptoxanthin, no evidence of a global impairment of antioxidative defenses or an enhancement of oxidative stress parameters was found.