Endothelial dysfunction is associated with atherogenesis and oxidative stress in humans. In rat and rabbit blood vessels, wine polyphenol antioxidants induce vascular relaxation in vitro through the NO-cGMP pathway. To assess the effect of a regular high-fat diet (HFD) and moderate red wine consumption on endothelial function (EF), a study was performed in healthy male volunteers. EF was measured as flow-mediated dilatation of the brachial artery, employing high-resolution ultrasound after an overnight fast. Other clinical and biochemical parameters related to EF were also measured. Six volunteers received a control diet, rich in fruits and vegetables (27% calories as fat) and five volunteers received an HFD (39.5% calories as fat). Measurements were done twice on each volunteer: after a period of 30 d with diet plus 240 mL of red wine/d, and after a period of 30 d with diet, without wine. In the absence of wine, there is a reduction of EF with HFD when compared to the control diet (P = 0.014). This loss of EF is not seen when both diets are supplemented with wine for 30 d (P = 0.001). Plasma levels of n-3 fatty acids (R2 = 0.232, P = 0.023) and lycopene (R2 = 0.223, P = 0.020) show a positive correlation with individual EF measurements, but they do not account for the significant differences observed among dietary groups or after wine supplementation. These results help elucidate the deleterious effect of a high-fat diet and the protective role of wine, n-3 fatty acids and dietary antioxidants in cardiovascular disease.

Context:The effects of medical and surgical treatments for obesity on peptide YY (PYY) levels, in patients with similar weight loss, remain unclear.Objective: The objective of the study was to assess PYY and appetite before and after Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG), and medical treatment (MED).Design: This was a prospective, controlled, nonrandomized study. Setting:The study was conducted at the Departments of Nutrition and Digestive Surgery at a university hospital.Participants: Participants included three groups of eight patients with similar body mass indexes (RYGB 37.8 Ϯ 0.8, SG 35.3 Ϯ 0.7, and MED 39.1 Ϯ 1.7 kg/m 2 , P ϭ NS) and eight lean controls (body mass index 21.7 Ϯ 0.7 kg/m 2 ). Main Outcome Measures:Total plasma PYY, hunger, and satiety visual analog scales in fasting and after ingestion of a standard test meal were measured.Results: At baseline there were no differences in the area under the curve (AUC) of PYY, hunger, or satiety in obese groups. Two months after the interventions, RYGB, SG, and MED groups achieved similar weight loss (17.7 Ϯ 3, 14.9 Ϯ 2.4, 16.6 Ϯ 4%, respectively, P ϭ NS). PYY AUC increased in RYGB (P Ͻ 0.001) and SG (P Ͻ 0.05) and did not change in MED. PYY levels decreased at fasting, 30 min, and 180 min after a standard test meal in MED (P Ͻ 0.05). Hunger AUC decreased in RYGB (P Ͻ 0.05). Satiety AUC increased in RYGB (P Ͻ 0.05) and SG (P Ͻ 0.05). Appetite did not change in MED. PYY AUC correlated with satiety AUC (r ϭ 0.35, P Ͻ 0.05).Conclusion: RYGB and SG increased PYY and reduced appetite. MED failed to produce changes. Different effects occur despite similar weight loss. This suggests that the weight-loss effects of these procedures are enhanced by an increase in PYY and satiety. O ver the last 30 yr, the prevalence of obesity has increased worldwide, becoming one of the world's most important public health problems and resulting in great efforts toward the development of strategies to treat this condition (1). However, medical interventions for obesity, including diet, physical activity, behavioral therapy, and weight loss drugs, are associated with poor weight reduction and are difficult to sustain in the long term (2). These modest results can be explained by several factors, one being that the human body responds to weight

Background: Postmenopausia and hypercholesterolemia are related to endothelial dysfunction, a pathogenic event in atherosclerosis. Soy protein reduces plasma cholesterol, but there is scanty information about its effect on endothelial function. Objective: To evaluate the effect of isolated soy protein compared to caseinate on plasma lipoproteins and endothelial function in postmenopausal hypercholesterolemic women. Design: Randomized, double-blind, cross-over trial. Setting: Outpatient clinic of the Catholic University of Chile. Subjects: Eighteen healthy, postmenopausal women with hypercholesterolemia were recruited, included and completed the protocol. Interventions: During the trial, all patients followed a low fat/low cholesterol diet and were randomly assigned to receive isolated soy protein or matching caseinate for 4 weeks, and then the alternative treatment until week 8. At pre-study and at the end of the first and second period, plasma lipoprotein levels and endothelial function (flow-mediated dilatation (FMD) of the brachial artery) were evaluated. Results: Plasma total and low density lipoprotein (LDL)-cholesterol concentration were significantly lower with the low fat/low cholesterol diet compared to pre-study, either with caseinate or soy protein. No significant differences in plasma lipid concentration between caseinate or soy protein interventions were observed. FMD did not change with the caseinate. In contrast, when soy protein was administered, FMD was significantly higher compared to pre-study (9.471.8% vs 5.371.2%; Po0.05) and compared to caseinate intervention (9.471.8% vs 4.971.5%; Po0.033). Conclusions: These results suggest that in postmenopausal hypercholesterolemic women, soy protein improves endothelial function, regardless of changes in plasma lipoproteins. Sponsorship: Pontificia Universidad Cató lica (DIPUC99/09E), Protein Technology International and Gynopharm Laboratory (Recalcine Group).

Weight loss by medical or surgical treatment improved insulin sensitivity. However, only MED corrected the hyperinsulinemic postprandial state associated to obesity. Postprandial GLP-1 levels increased significantly after SG without duodenal exclusion, which may explain why insulin secretion did not decrease following this surgery.

The activities of Na-K-ATPase and Na-K-2Cl cotransporter (NKCC1) were studied in the aorta, heart, and skeletal muscle of streptozotocin (STZ)-induced diabetic rats and control rats. In the aortic rings of STZ rats, the Na-K-ATPase-dependent (86)Rb/K uptake was reduced to 60.0 +/- 5.5% of the control value (P < 0.01). However, Na-K-ATPase activity in soleus skeletal muscle fibers of STZ rats and paired control rats was similar, showing that the reduction of Na-K-ATPase activity in aortas of STZ rats is tissue specific. To functionally distinguish the contributions of ouabain-resistant (alpha(1)) and ouabain-sensitive (alpha(2) and alpha(3)) isoforms to the Na-K-ATPase activity in aortic rings, we used either a high (10(-3) M) or a low (10(-5) M) ouabain concentration during (86)Rb/K uptake. We found that the reduction in total Na-K-ATPase activity resulted from a dramatic decrement in ouabain-sensitive mediated (86)Rb/K uptake (26.0 +/- 3.9% of control, P < 0.01). Western blot analysis of membrane fractions from aortas of STZ rats demonstrated a significant reduction in protein levels of alpha(1)- and alpha(2)-catalytic isoforms (alpha(1) = 71.3 +/- 9.8% of control values, P < 0.05; alpha(2) = 44.5 +/- 11.3% of control, P < 0.01). In contrast, aortic rings from the STZ rats demonstrated an increase in NKCC1 activity (172.5 +/- 9.5%, P < 0.01); however, in heart tissue no difference in NKCC1 activity was seen between control and diabetic animals. Transport studies of endothelium-denuded or intact aortic rings demonstrated that the endothelium stimulates both Na-K-ATPase and Na-K-2Cl dependent (86)Rb/K uptake. The endothelium-dependent stimulation of Na-K-ATPase and Na-K-2Cl was not hampered by diabetes. We conclude that abnormal vascular vessel tone and function, reported in STZ-induced diabetic rats, may be related to ion transport abnormalities caused by changes in Na-K-ATPase and Na-K-2Cl activities.

Evaluation of a pilot intervention program for overweight and obese adults at risk of type 2 diabetes Background: The Ministry of Health of Chile and selected obesity specialized centers implemented an interdisciplinary pilot program for overweight adults at risk of diabetes to decrease the risk of type 2 diabetes (T2D) and cardiovascular risk factors (CVRF). Aim: To assess the results of this program. Patients and methods: Beneficiaries of the public primary health system aged 18-45 years, with a body mass index (BMI) 25-38 kg/m 2 and fasting blood glucose 100-125 mg/dL or with any direct family member with T2D, were recruited. During the four months of the study, they were scheduled for three physician visits, four dietitian consultations, 14 physical activity sessions and four group workshops (two with a psychologist or therapist). In fasting blood samples, at the beginning and at the fourth month, glucose, insulin and lipids were determined. The Homeostasis model assessment (HOMA) index was calculated. Results: Two hundred-seventy-six patients were recruited and 160 (141 women), completed the four months of follow up. In this subgroup, at the start and end of the intervention, a BMI equal to or greater than 30 kg/m 2 was observed in 69% and 52% of subjects respectively, a systolic blood pressure equal to or greater than 140 mm Hg was observed in 24% and 6% respectively, a diastolic blood pressure equal to or greater than 90 mm Hg was observed in 28% and 9% respectively, a blood glucose equal to or greater than 100 mg/dL was observed in 61% and 19% respectively, a plasma insulin equal to or greater than 12,5 µUI/ml was observed in 49% and 34% respectively and a HOMA equal to or greater than 2.5 was observed in 63% and 42% respectively (all these comparisons are significant with a p <0.05). Conclusions: In those patients that completed the follow up period, this intervention induced a significant decrease of some CVRF, such as BMI, fasting glucose levels and HOMA index

Sarcoplasmic reticulum membrane vesicles isolated from frog skeletal muscle display high conductance calcium channels when fused into phospholipid bilayers. The channels are selective for calcium and barium over Tris. The fractional open time was voltage-independent (-40 to +25 mV), but was steeply dependent on the free cis [Ca2+] (P0 = 0.02 at 10 microM cis Ca2+ and 0.77 at 150 microM Ca2+; estimated Hill coefficient: 1.6). Addition of ATP (1 mM; cis) further increased P0 from 0.77 to 0.94. Calcium activation was reversed by addition of EGTA to the cis compartment. Magnesium (2 mM) increased the frequency of rapid closures and 8 mM magnesium decreased the current amplitude from 3.4 to 1.2 pA at 0 mV, suggesting a reversible fast blockade. Addition of increasing concentrations of inositol (1, 4, 5)-triphosphate (cis), increased P0 from 0.10 +/- 0.01 (mean +/- SEM) in the control to 0.85 +/- 0.02 at 50 microM in an approximately sigmoidal fashion, with an apparent half-maximal activation at 15 microM inositol (1, 4, 5)-trisphosphate in the presence of 40 microM cis Ca2+. Lower concentrations of this agonist were required to produce a significant increase in P0 when 10 microM or less cis Ca2+ were used. The channel was blocked by the addition to the cis compartment of either 0.5 mM lanthanum, 0.5 microM ruthenium red, or 200 nM ryanodine, all known inhibitors of Ca2+ release from sarcoplasmic reticulum vesicles. These results demonstrate the presence of calcium channels in the sarcoplasmic reticulum from frog skeletal muscle with a pharmacological profile consistent with a role in excitation contraction coupling and with the hypothesis that inositol ( 1,4,5)-trisphosphate is a physiological agonist in this process.

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