A new class of glycomimetic drugs to prevent free fatty acid-induced endothelial dysfunction

Background: Carbohydrates play a major role in cell signaling in many biological processes. We have developed a set of glycomimetic drugs that mimic the structure of carbohydrates and represent a novel source of therapeutics for endothelial dysfunction, a key initiating factor in cardiovascular complications. Purpose: Our objective was to determine the protective effects of small molecule glycomimetics against free fatty acid­induced endothelial dysfunction, focusing on nitric oxide (NO) and oxidative stress pathways. Methods: Four glycomimetics were synthesized by the stepwise transformation of 2,5­dihydroxybenzoic acid to a range of 2,5­substituted benzoic acid derivatives, incorporating the key sulfate groups to mimic the interactions of heparan sulfate. Endothelial function was assessed using acetylcholine­induced, endotheliumdependent relaxation in mouse thoracic aortic rings using wire myography. Human umbilical vein endothelial cell (HUVEC) behavior was evaluated in the presence or absence of the free fatty acid, palmitate, with or without glycomimetics (1µM). DAF­2 and H2DCF­DA assays were used to determine nitric oxide (NO) and reactive oxygen species (ROS) production, respectively. Lipid peroxidation colorimetric and antioxidant enzyme activity assays were also carried out. RT­PCR and western blotting were utilized to measure Akt, eNOS, Nrf­2, NQO­1 and HO­1 expression. Results: Ex vivo endothelium­dependent relaxation was significantly improved by the glycomimetics under palmitate­induced oxidative stress. In vitro studies showed that the glycomimetics protected HUVECs against the palmitate­induced oxidative stress and enhanced NO production. We demonstrate that the protective effects of pre­incubation with glycomimetics occurred via upregulation of Akt/eNOS signaling, activation of the Nrf2/ARE pathway, and suppression of ROS­induced lipid peroxidation. Conclusion: We have developed a novel set of small molecule glycomimetics that protect against free fatty acidinduced endothelial dysfunction and thus, represent a new category of therapeutic drugs to target endothelial damage, the first line of defense against cardiovascular disease

Grain size composition of metalliferous sediments from the East Pacific Rise axial zone at 21°S

It is shown that a laser granulometric analysis makes it possible to obtain adequate results with respect to grain size composition of metalliferous sediments in contrast to water-mechanical types of analysis. Metalliferous sediments of the studied region are usually represented by pelitic (<0.01 mm) oozes, less frequently by silty-pelitic and fine silt oozes

Optimization of formulations with balanced biochemical composition and possibilities for their extrusion

Abstract. Combinations of different raw materials (beans, einkorn wheat, and buckwheat) for obtaining formulations with high protein content and balanced amino acid composition were studied using simplex centroid design. The target functions for optimization were content of protein, sulfur-containing amino acid methionine and cysteine, lysine, and tryptophan. The optimal area of combinations of raw materials in the food formulas with balanced biochemical composition was obtained. Optimized ternary mixture consisting of 50% bean, 40% einkorn wheat, and 10% buckwheat with different moisture content (16, 22, and 28%) has been extruded in a laboratory single screw extruder (Brabender 20 DN, Germany). Extrusion parameters were as follows: feed screw speed 50 rpm, die diameter 3 mm, screw compression ratio 2:1, temperature profile 100/140/160ºC, screw speed 160 rpm. The three extrudates with different initial moisture were evaluated by sectional expansion index, water absorption index, water solubility index, and density, with the aim of choosing the best treatment. The results demonstrated that the 22% initial moisture content yielded an extrudate with good physicochemical characteristics overall but an optimization study is needed to confirm this

The sarcopenia and physical frailty in older people: multi-component treatment strategies (SPRINTT) project: description and feasibility of a nutrition intervention in community-dwelling older Europeans

Background: The “Sarcopenia and Physical Frailty in Older People: Multicomponent Treatment Strategies” (SPRINTT) project sponsored a multi-center randomized controlled trial (RCT) with the objective to determine the effect of physical activity and nutrition intervention for prevention of mobility disability in community-dwelling frail older Europeans. We describe here the design and feasibility of the SPRINTT nutrition intervention, including techniques used by nutrition interventionists to identify those at risk of malnutrition and to carry out the nutrition intervention. Methods: SPRINTT RCT recruited older adults (≥ 70&nbsp;years) from 11 European countries. Eligible participants (n = 1517) had functional limitations measured with Short Physical Performance Battery (SPPB score 3–9) and low muscle mass as determined by DXA scans, but were able to walk 400&nbsp;m without assistance within 15&nbsp;min. Participants were followed up for up to 3 years. The nutrition intervention was carried out mainly by individual nutrition counseling. Nutrition goals included achieving a daily protein intake of 1.0–1.2&nbsp;g/kg body weight, energy intake of 25–30&nbsp;kcal/kg of body weight/day, and serum vitamin D concentration ≥ 75&nbsp;mmol/L. Survey on the method strategies and feasibility of the nutrition intervention was sent to all nutrition interventionists of the 16 SPRINTT study sites. Results: Nutrition interventionists from all study sites responded to the survey. All responders found that the SPRINTT nutrition intervention was feasible for the target population, and it was well received by the majority. The identification of participants at nutritional risk was accomplished by combining information from interviews, questionnaires, clinical and laboratory data. Although the nutrition intervention was mainly carried out using individual nutritional counselling, other assisting methods were used as appropriate. Conclusion: The SPRINTT nutrition intervention was feasible and able to adapt flexibly to varying needs of this heterogeneous population. The procedures adopted to identify older adults at risk of malnutrition and to design the appropriate intervention may serve as a model to deliver nutrition intervention for community-dwelling older people with mobility limitations