Arginine and Lysine Supplementation Potentiates the Beneficial ß-Hydroxy ß-Methyl Butyrate (HMB) Effects on Skeletal Muscle in a Rat Model of Diabetes.

Skeletal muscle is the key tissue for maintaining protein and glucose homeostasis, having a profound impact on the development of diabetes. Diabetes causes deleterious changes in terms of loss of muscle mass, which will contribute to reduced glucose uptake and therefore progression of the disease. Nutritional approaches in diabetes have been directed to increase muscle glucose uptake, and improving protein turnover has been at least partially an oversight. In muscle, ß-hydroxy ß-methyl butyrate (HMB) promotes net protein synthesis, while arginine and lysine increase glucose uptake, albeit their effects on promoting protein synthesis are limited. This study evaluates if the combination of HMB, lysine, and arginine could prevent the loss of muscle mass and function, reducing the progression of diabetes. Therefore, the combination of these ingredients was tested in vitro and in vivo. In muscle cell cultures, the supplementation enhances glucose uptake and net protein synthesis due to an increase in the amount of GLUT4 transporter and stimulation of the insulin-dependent signaling pathway involving IRS-1 and Akt. In vivo, using a rat model of diabetes, the supplementation increases lean body mass and insulin sensitivity and decreases blood glucose and serum glycosylated hemoglobin. In treated animals, an increase in GLUT4, creatine kinase, and Akt phosphorylation was detected, demonstrating the synergic effects of the three ingredients. Our findings showed that nutritional formulations based on the combination of HMB, lysine, and arginine are effective, not only to control blood glucose levels but also to prevent skeletal muscle atrophy associated with the progression of diabetes.

Quality More Than Quantity: The Use of Carbohydrates in High-Fat Diets to Tackle Obesity in Growing Rats.

Childhood obesity prevention is important to avoid obesity and its comorbidities into adulthood. Although the energy density of food has been considered a main obesogenic factor, a focus on food quality rather that the quantity of the different macronutrients is needed. Therefore, this study investigates the effects of changing the quality of carbohydrates from rapidly to slowly digestible carbohydrates on metabolic abnormalities and its impact on obesity in growing rats fed a high-fat diet (HFD). Growing rats were fed on HFD containing carbohydrates with different digestion rates: a HFD containing rapid-digesting carbohydrates (OBE group) or slow-digesting carbohydrates (ISR group), for 4 weeks and the effect on the metabolism and signaling pathways were analyzed in different tissues. Animals from OBE group presented an overweight/obese phenotype with a higher body weight gain and greater accumulation of fat in adipose tissue and liver. This state was associated with an increase of HOMA index, serum diacylglycerols and triacylglycerides, insulin, leptin, and pro-inflammatory cytokines. In contrast, the change of carbohydrate profile in the diet to one based on slow digestible prevented the obesity-related adverse effects. In adipose tissue, GLUT4 was increased and UCPs and PPARγ were decreased in ISR group respect to OBE group. In liver, GLUT2, FAS, and SRBP1 were lower in ISR group than OBE group. In muscle, an increase of glycogen, GLUT4, AMPK, and Akt were observed in comparison to OBE group. In conclusion, this study demonstrates that the replacement of rapidly digestible carbohydrates for slowly digestible carbohydrates within a high-fat diet promoted a protective effect against the development of obesity and its associated comorbidities.

Sistema informático para la evaluación del control externo de la calidad en laboratorios clínicos (PRICECLAB) / Computer system for the evaluation of external quality control in clinical laboratories (PRICECLAB)

RESUMEN Introducción: las tecnologías de la información favorecen la calidad, seguridad, eficiencia y productividad de los servicios de salud. Su utilización en los laboratorios clínicos modernos es una necesidad actual debido a una creciente solicitud de exámenes, nuevas prestaciones y mayores exigencias en términos de la calidad de los mismos. Objetivo: desarrollar un sistema informático que contribuya al perfeccionamiento del proceso de evaluación del control externo de la calidad para Laboratorios Clínicos en Pinar del Río. Métodos: investigación de desarrollo tecnológico que define el proceso de implementación de una aplicación web a partir de la información recopilada como parte de la evaluación externa de la calidad de laboratorios clínicos en unidades del sistema provincial de salud en Pinar del Río. Se definen además las tecnologías empleadas para el diseño e implementación de la aplicación web. Resultados: el sistema informático ofrece a los laboratorios la posibilidad de completar su esquema de Control Interno con una estimación objetiva de la calidad de sus procedimientos de medida. El sistema permite estimar la variabilidad interlaboratorio, así como comparar y evaluar métodos, de manera que se logre demostrar el desempeño del laboratorio y orientar sobre posibles causas de error. Conclusiones: el sistema informático resultado de la investigación favorece la toma de decisiones, así como, la mejora de los estándares de calidad en el proceso de control externo de los laboratorios clínicos mediante el uso de las Tecnologías de la Informática y las Comunicaciones, como parte de la Política de informatización del país.

ABSTRACT Introduction: information Technologies favour the quality, safety, efficiency and productivity of health services. Its use in modern clinical laboratories is a current need due to a growing demand for examinations, new services and greater demands in terms of their quality. Objective: to develop a computer system that contributes to the improvement of the external quality control evaluation process for Clinical Laboratories in Pinar del Río. methods: technological development research that defines the implementation process of a web application based on the information gathered as part of the external quality evaluation of clinical laboratories in units of the provincial health system in Pinar del Río. The technologies used for the design and implementation of the web application are also defined. Results: the computer system offers laboratories the possibility of completing their Internal Control scheme with an objective estimation of the quality of their measurement procedures. The system allows to estimate the interlaboratory variability, as well as to compare and evaluate methods, in order to demonstrate the performance of the laboratory and to guide on possible causes of error. Conclusions: the computer system resulting from the research favors decision making, as well as the improvement of quality standards in the process of external control of clinical laboratories through the use of Information Technology and Communications, as part of the country's computerization policy.

Programming Skeletal Muscle Metabolic Flexibility in Offspring of Male Rats in Response to Maternal Consumption of Slow Digesting Carbohydrates during Pregnancy.

Skeletal muscle plays a relevant role in metabolic flexibility and fuel usage and the associated muscle metabolic inflexibility due to high-fat diets contributing to obesity and type 2 diabetes. Previous research from our group indicates that a high-fat and rapid-digesting carbohydrate diet during pregnancy promotes an excessive adipogenesis and also increases the risk of non-alcoholic fatty liver disease in the offspring. This effect can be counteracted by diets containing carbohydrates with similar glycemic load but lower digestion rates. To address the role of the skeletal muscle in these experimental settings, pregnant rats were fed high-fat diets containing carbohydrates with similar glycemic load but different digestion rates, a high fat containing rapid-digesting carbohydrates diet (HF/RD diet) or a high fat containing slow-digesting carbohydrates diet (HF/SD diet). After weaning, male offspring were fed a standard diet for 3 weeks (weaning) or 10 weeks (adolescence) and the impact of the maternal HF/RD and HF/SD diets on the metabolism, signaling pathways and muscle transcriptome was analyzed. The HF/SD offspring displayed better muscle features compared with the HF/RD group, showing a higher muscle mass, myosin content and differentiation markers that translated into a greater grip strength. In the HF/SD group, metabolic changes such as a higher expression of fatty acids (FAT/CD36) and glucose (GLUT4) transporters, an enhanced glycogen content, as well as changes in regulatory enzymes such as muscle pyruvate kinase and pyruvate dehydrogenase kinase 4 were found, supporting an increased muscle metabolic flexibility and improved muscle performance. The analysis of signaling pathways was consistent with a better insulin sensitivity in the muscle of the HF/SD group. Furthermore, increased expression of genes involved in pathways leading to muscle differentiation, muscle mass regulation, extracellular matrix content and insulin sensitivity were detected in the HF/SD group when compared with HF/RD animals. In the HF/SD group, the upregulation of the ElaV1/HuR gene could be one of the main regulators in the positive effects of the diet in early programming on the offspring. The long-lasting programming effects of the HF/SD diet during pregnancy may depend on a coordinated gene regulation, modulation of signaling pathways and metabolic flexibility that lead to an improved muscle functionality. The dietary early programming associated to HF/SD diet has synergic and positive crosstalk effects in several tissues, mainly muscle, liver and adipose tissue, contributing to maintain the whole body homeostasis in the offspring.

A Slow-Digesting Carbohydrate Diet during Rat Pregnancy Protects Offspring from Non-Alcoholic Fatty Liver Disease Risk through the Modulation of the Carbohydrate-Response Element and Sterol Regulatory Element Binding Proteins.

High-fat (HF) and rapid digestive (RD) carbohydrate diets during pregnancy promote excessive adipogenesis in offspring. This effect can be corrected by diets with similar glycemic loads, but low rates of carbohydrate digestion. However, the effects of these diets on metabolic programming in the livers of offspring, and the liver metabolism contributions to adipogenesis, remain to be addressed. In this study, pregnant insulin-resistant rats were fed high-fat diets with similar glycemic loads but different rates of carbohydrate digestion, High Fat-Rapid Digestive (HF-RD) diet or High Fat-Slow Digestive (HF-SD) diet. Offspring were fed a standard diet for 10 weeks, and the impact of these diets on the metabolic and signaling pathways involved in liver fat synthesis and storage of offspring were analyzed, including liver lipidomics, glycogen and carbohydrate and lipid metabolism key enzymes and signaling pathways. Livers from animals whose mothers were fed an HF-RD diet showed higher saturated triacylglycerol deposits with lower carbon numbers and double bond contents compared with the HF-SD group. Moreover, the HF-RD group exhibited enhanced glucose transporter 2, pyruvate kinase (PK), acetyl coenzyme A carboxylase (ACC) and fatty acid (FA) synthase expression, and a decrease in pyruvate carboxylase (PyC) expression leading to an altered liver lipid profile. These parameters were normalized in the HF-SD group. The changes in lipogenic enzyme expression were parallel to changes in AktPKB phosphorylation status and nuclear expression in carbohydrate-response element and sterol regulatory element binding proteins. In conclusion, an HF-RD diet during pregnancy translates to changes in liver signaling and metabolic pathways in offspring, enhancing liver lipid storage and synthesis, and therefore non-alcoholic fatty liver disease (NAFLD) risk. These changes can be corrected by feeding an HF-SD diet during pregnancy.

Feeding a slowly digestible carbohydrate diet during pregnancy of insulin-resistant rats prevents the excess of adipogenesis in their offspring.

An obesogenic environment during pregnancy has been shown to increase the risk of dysregulation on adipogenesis and insulin resistance in the offspring. Being essential for the growing fetus, glucose supply is guaranteed by a number of modifications in the mother's metabolism, and thus, glucose control during pregnancy especially among obese or diabetic women is paramount to prevent adverse consequences in their children. Besides the election of low-glycemic-index carbohydrates, the rate of carbohydrate digestion could be relevant to keep a good glucose control. In the present study, we compared the effects of two high-fat diets with similar glycemic load but different rates of carbohydrate digestion given to pregnant insulin-resistant rats. After birth, all animals were fed a standard diet until age 14 weeks. We analyzed offspring body composition, plasma and adipocyte lipidomics, lipid metabolism in adipose tissue and insulin sensitivity. Those animals whose mothers were fed the rapid-digesting carbohydrate diet exhibited an excessive adipogenesis. Thus, these animals showed a marked lipidemia, increased lipid synthesis in the adipose tissue and reduced glucose transporter amount in the adipose. On the contrary, those animals whose mothers were fed the slow-digesting carbohydrate diet showed a profile in the measured parameters closer to that of the offspring of healthy mothers. These results support the hypothesis that not only glycemic index but the rate of carbohydrate digestion during gestation may be critical to regulate the programming of adipogenesis in the offspring.

The effects of person-related and environmental factors on consumers' decision-making in agri-food markets: The case of olive oils.

Refined olive oil (ROO) and extra virgin olive oil (EVOO) categories are different products with respect to their objective quality. Nevertheless, this quality gap is not reflected in the purchase behaviour of consumers in Spain, which is the main producer country worldwide. On the basis of economic theory, the price gap could be a part of the explanation; however, the objective price gap between EVOO and ROO has been on average around €0.40 kg-1 since the 2007/2008 crop year in Spain. Therefore, this paper contributes to a more in-depth understanding of those factors, besides price, affecting consumers' decision-making process in olive oil markets. We examine how consumers build their purchase preferences towards two products - namely EVOO and ROO-based on their evaluative judgements shaped by person-related and environmental factors. In doing so, a theoretical model is proposed and an empirical application in southern Spain is presented, using variance-based structural equation modelling (SEM) by means of partial least squares path modelling (PLS). The results show how attitude towards EVOO and ROO play a key role in explaining both EVOO and ROO consumption. In addition, taste preferences are shown to have an overriding moderator effect on the relationship between attitude towards ROO and consumption. Negative anticipated consequences regarding EVOO are core to shape consumers' attitude towards ROO and also influence attitude towards the own product. Meanwhile, healthy shopping habits affect mainly attitude towards EVOO and the perceived value of private brands influences attitude towards ROO.

Survey data on consumer behaviour in olive oil markets: The role of product knowledge and brand credence.

This paper presents data conducted to analyse consumer behaviour in agri-food markets, where product differentiation failures occur, with the aim of disentangling the roles played by both consumer information and inferences made from informational stimuli. We thus examined consumer knowledge structures and brand credence related to attitudes towards a particular foodstuff and a product alternative, as well as the actual consumption of the foodstuff. To do so, the selected case study was the olive oil markets in Spain, given that products such as extra virgin olive oil (EVOO) and refined olive oil (ROO), that differ in terms of intrinsic features, become undifferentiated. The data of the observed variables were collected from 700 regular buyers from an online panel at the household level in southern Spain. The data were processed using both Excel for checking, cleaning and descriptive purposes and ADANCO 2.0 (Dijkstra and Henseler, 2015) [1] for performing the model estimations.

The Canary Islands as a model of risk of pulmonary dirofilariasis in a hyperendemic area.

We assessed the risk of human pulmonary dirofilariasis in the Canary Islands, hyperendemic for canine heartworm (Dirofilaria immitis), a zoonotic vector-borne infection. For this purpose, 1479 inhabitants were tested for anti-D. immitis antibodies. Four of the 7 islands presented high seroprevalences (from 6.2 to 12.7%), therefore high exposure to the parasite and risk of zoonotic infection. These corresponded to those islands with high canine prevalences of dirofilariasis and favourable climatic conditions for the development of mosquito vectors. The lowest prevalences (from 0 to 1.6%) were found in the desert islands and those with low canine prevalences of heartworm. Seroprevalences were very variable inside each island as well, being related to the climate and demographic factors. Human pulmonary dirofilariasis is an emerging zoonosis worldwide which frequently goes undiagnosed. Serological studies could be useful for the correct evaluation of the risk of infection among the human population, and study of the health implications of the continuous contact with the parasite in endemic areas. Sanitary authorities should be aware of the current epidemiological data, and physicians should include human dirofilariasis in the differential diagnosis of pulmonary nodules.

ß-Hydroxy-ß-Methylbutyrate (HMB) Promotes Neurite Outgrowth in Neuro2a Cells.

ß-Hydroxy-ß-methylbutyrate (HMB) has been shown to enhance cell survival, differentiation and protein turnover in muscle, mainly activating phosphoinositide-3-kinase/protein kinase B (PI3K/Akt) and mitogen-activated protein kinases/ extracellular-signal-regulated kinases (MAPK/ERK) signaling pathways. Since these two pathways are related to neuronal survival and differentiation, in this study, we have investigated the neurotrophic effects of HMB in mouse neuroblastoma Neuro2a cells. In Neuro2a cells, HMB promotes differentiation to neurites independent from any effects on proliferation. These effects are mediated by activation of both the PI3K/Akt and the extracellular-signal-regulated kinases (ERK1/2) signaling as demonstrated by the use of specific inhibitors of these two pathways. As myocyte-enhancer factor 2 (MEF2) family of transcription factors are involved in neuronal survival and plasticity, the transcriptional activity and protein levels of MEF2 were also evaluated. HMB promoted MEF2-dependent transcriptional activity mediated by the activation of Akt and ERK1/2 pathways. Furthermore, HMB increases the expression of brain glucose transporters 1 (GLUT1) and 3 (GLUT3), and mTOR phosphorylation, which translates in a higher protein synthesis in Neuro2a cells. Furthermore, Torin1 and rapamycin effects on MEF2 transcriptional activity and HMB-dependent neurite outgrowth support that HMB acts through mTORC2. Together, these findings provide clear evidence to support an important role of HMB in neurite outgrowth.

ß-Hydroxy-ß-methylbutyrate (HMB) normalizes dexamethasone-induced autophagy-lysosomal pathway in skeletal muscle.

Dexamethasone-induced muscle atrophy is due to an increase in protein breakdown and a decrease in protein synthesis, associated with an over-stimulation of the autophagy-lysosomal pathway. These effects are mediated by alterations in IGF-1 and PI3K/Akt signaling. In this study, we have investigated the effects of ß-Hydroxy-ß-methylbutyrate (HMB) on the regulation of autophagy and proteosomal systems. Rats were treated during 21 days with dexamethasone as a model of muscle atrophy. Co-administration of HMB attenuated the effects promoted by dexamethasone. HMB ameliorated the loss in body weight, lean mass and the reduction of the muscle fiber cross-sectional area (shrinkage) in gastrocnemius muscle. Consequently, HMB produced an improvement in muscle strength in the dexamethasone-treated rats. To elucidate the molecular mechanisms responsible for these effects, rat L6 myotubes were used. In these cells, HMB significantly attenuated lysosomal proteolysis induced by dexamethasone by normalizing the changes observed in autophagosome formation, LC3 II, p62 and Bnip3 expression after dexamethasone treatment. HMB effects were mediated by an increase in FoxO3a phosphorylation and concomitant decrease in FoxO transcriptional activity. The HMB effect was due to the restoration of Akt signaling diminished by dexamethasone treatment. Moreover, HMB was also involved in the regulation of the activity of ubiquitin and expression of MurF1 and Atrogin-1, components of the proteasome system that are activated or up-regulated by dexamethasone. In conclusion, in vivo and in vitro studies suggest that HMB exerts protective effects against dexamethasone-induced muscle atrophy by normalizing the Akt/FoxO axis that controls autophagy and ubiquitin proteolysis.

Activation of ERK by sodium tungstate induces protein synthesis and prevents protein degradation in rat L6 myotubes.

The balance between the rates of protein synthesis and degradation in muscle is regulated by PI3K/Akt signaling. Here we addressed the effect of ERK activation by sodium tungstate on protein turnover in rat L6 myotubes. Phosphorylation of ERK by this compound increased protein synthesis by activating MTOR and prevented dexamethasone-induced protein degradation by blocking FoxO3a activity, but it did not alter Akt phosphorylation. Thus, activation of ERK by tungstate improves protein turnover in dexamethasone-treated cells. On the basis of our results, we propose that tungstate be considered an alternative to IGF-I and its analogs in the prevention of skeletal muscle atrophy.

Regional variations of µTBS of light- and chemically cured resin composite restorations in clinically relevant situations.

PURPOSE: To test whether the distance to the mass center of a buildup made of visible-light- or chemically curing composite resin bonded to dentin and cured in one increment has an influence on µTBS. MATERIALS AND METHODS: In the experimental groups, one-increment visible-light (Z250) or chemically-cured (TiCore) composite-resins buildups were bonded to flattened bovine dentin surfaces. In the control groups, the same materials were bonded as separate buildups on circumscribed areas to minimize the effect of shearing polymerization contraction. Compound composite/interface/dentin specimens were trimmed out of buildups and tested in tension until detachment; the distances to the mass centers of their respective buildups were recorded as the independent variable. The correlation between µTBS and distances was tested in each group. Slopes and intercepts of regression lines (µTBS to bonded area) were compared in the experimental groups. RESULTS: The correlation between µTBS and distances was negative and statistically significant for both experimental groups (p < 0.0001), but not for the two control groups (p > 0.34). CONCLUSION: In clinical situations such as direct resin veneering or resin core construction, where a first layer of a light- or chemically cured resin composite is bonded and cured on a broad surface, the µTBS of the interface decreases proportionally to the distance to the mass center of the restoration.

Microtensile bond strength distributions of three composite materials with different polymerization shrinkages bonded to dentin.

PURPOSE: To assess the detrimental effects that polymerization contraction causes on the interfacial microtensile bond strength (µTBS) to dentin of three light-curing resin composites: two conventional bis-GMA-based composite resins (Filtek Z250, TPH Spectrum) and a low shrinkage material (Filtek Silorane [SIL]). MATERIALS AND METHODS: Flat surfaces of labial dentin were made in 46 bovine teeth and restored in single (group A) or in three separate (group B) one-increment visible-light cured resin composite blocks, with similar locations among teeth. After 24 h, restored teeth were sectioned perpendicular to interfaces, producing rectangular compound specimens (385 specimens were produced in group A, and 132 in group B), and submitted to tension (crosshead speed 1mm/min) until failure. µTBS results were adjusted to bonded area and transformed to percentages of maximum values within each tooth (PTens). In A groups, distances of specimens to the gingival ends of each restoration were transformed to PDistances: the percentage of that distance within its specimen. RESULTS: Spearman's nonparametric correlation test showed that for Z250, TPH and SIL, in A groups, a material's correlation coefficient was positive for the first half of restorations (0% to 50% PDistances) and negative for the second (50% to 100%). For all materials, PTens values in extremes of restorations (pooled 0 and 100% PDistances) in A groups were smaller than corresponding values in B groups. These differences were statistically significantly (Student's t-test) only for Z250 and TPH. CONCLUSION: Even in cases of favorable configuration factor, polymerization shrinkage in large restorations can reduce interface mechanical characteristics. The relevance of this decrease has still to be established.

Effects of polymerization contraction on interface's microTBS of luting material and dentin.

Polymerization contraction of composite resin luting materials is known to produce high stresses in the interfaces being cemented that are described as perpendicular to them. This study describes the effect of shearing strains of curing luting materials on microtensile bond strength (microTBS) of interfaces. A flat surface of labial dentin of bovine incisors was exposed and teeth randomly assigned to A (n = 12) or B (n = 6) groups. Adoro rectangular (2 x 3 x 11 mm) restorative composite resin blocks were cemented (Excite DSC + Variolink II) completely (group A) or partially (group B, only on extremes and center) occupying luting space. After visible light curing, stick compound bars were sectioned perpendicular to interface and submitted to tension until detachment. microTBS decreased from the center to the extremes in group A (Spearman tests p < 0.0008) and not in group B, where microTBS was higher in extremes than in correspondent locations in group A and equivalent to that in group A in the central location. Weibull's analysis showed that m modulus and characteristic stresses also decreased from the center to periphery of restorations in group A. Mechanical resistance of bonded interface of a luting material and dentin decreases peripherally, and this reduction is caused by polymerization contraction.

Manejo nutricional en corrales de engorda / Nutritional management in feedlot

El manejo nutricional en un corral de engorda debe enfocarse a los siguientes aspectos: recepción, prevención de acidosis, uso de aditivos alimenticios, agente anabólicos y programas de finalización. El uso de aditivos es una de las alternativas más importantes para reducir los costos de alimentación o para obtener mayor eficiencia alimenticia. Algunos de ellos tienen efectos secundarios como la reducción de acidosis y coccidiosis, otros reducen la incidencia de abscesos hepáticos y problemas de salud animal. La tasa de degradación de almidón es muy importante en la selección del grano para el programa de nutrición del corral de engorda