Dietary restriction abrogates antibody production induced by a DNA vaccine encoding the mycobacterial 65 kDa heat shock protein

Abstract Background Protein-calorie malnutrition (PCM) is the most common type of malnutrition. PCM leads to immunodeficiency and consequent increased susceptibility to infectious agents. In addition, responses to prophylactic vaccines depend on nutritional status. This study aims to evaluate the ability of undernourished mice to mount an immune response to a genetic vaccine (pVAXhsp65) against tuberculosis, containing the gene coding for the heat shock protein 65 from mycobacteria. Methods Young adult female BALB/c mice were fed ad libitum or with 80% of the amount of food consumed by a normal diet group. We initially characterized a mice model of dietary restriction by determining body and spleen weights, hematological parameters and histopathological changes in lymphoid organs. The ability of splenic cells to produce IFN-gamma and IL-4 upon in vitro stimulation with LPS or S. aureus and the serum titer of specific IgG1 and IgG2a anti-hsp65 antibodies after intramuscular immunization with pVAXhsp65 was then tested. Results Dietary restriction significantly decreased body and spleen weights and also the total lymphocyte count in blood. This restriction also determined a striking atrophy in lymphoid organs as spleen, thymus and lymphoid tissue associated with the small intestine. Specific antibodies were not detected in mice submitted to dietary restriction whereas the well nourished animals produced significant levels of both, IgG1 and IgG2a anti-hsp65. Conclusion 20% restriction in food intake deeply compromised humoral immunity induced by a genetic vaccine, alerting, therefore, for the relevance of the nutritional condition in vaccination programs based on these kinds of constructs.

Efficacy of the dietary histone deacetylase inhibitor butyrate alone or in combination with vitamin A against proliferation of MCF-7 human breast cancer cells

The combined treatment with histone deacetylase inhibitors (HDACi) and retinoids has been suggested as a potential epigenetic strategy for the control of cancer. In the present study, we investigated the effects of treatment with butyrate, a dietary HDACi, combined with vitamin A on MCF-7 human breast cancer cells. Cell proliferation was evaluated by the crystal violet staining method. MCF-7 cells were plated at 5 x 10(4) cells/mL and treated with butyrate (1 mM) alone or combined with vitamin A (10 µM) for 24 to 120 h. Cell proliferation inhibition was 34, 10 and 46% following treatment with butyrate, vitamin A and their combination, respectively, suggesting that vitamin A potentiated the inhibitory activities of butyrate. Furthermore, exposure to this short-chain fatty acid increased the level of histone H3K9 acetylation by 9.5-fold (Western blot), but not of H4K16, and increased the expression levels of p21WAF1 by 2.7-fold (Western blot) and of RARβ by 2.0-fold (quantitative real-time PCR). Our data show that RARβ may represent a molecular target for butyrate in breast cancer cells. Due to its effectiveness as a dietary HDACi, butyrate should be considered for use in combinatorial strategies with more active retinoids, especially in breast cancers in which RARβ is epigenetically altered.

Aerobic exercise training induces metabolic benefits in rats with metabolic syndrome independent of dietary changes

OBJECTIVES: We evaluated the effects of aerobic exercise training without dietary changes on cardiovascular and metabolic variables and on the expression of glucose transporter Type 4 in rats with metabolic syndrome. METHODS: Twenty male spontaneously hypertensive rats received monosodium glutamate during the neonatal period. The animals were allocated to the following groups: MS (sedentary metabolic syndrome), MS-T (trained on a treadmill for 1 hour/day, 5 days/week for 10 weeks), H (sedentary spontaneously hypertensive rats) and H-T (trained spontaneously hypertensive rats). The Lee index, blood pressure (tail-cuff system), insulin sensitivity (insulin tolerance test) and functional capacity were evaluated before and after 10 weeks of training. Glucose transporter Type 4 expression was analyzed using Western blotting. The data were compared using analysis of variance (ANOVA) (p<0.05). RESULTS: At baseline, the MS rats exhibited lower insulin sensitivity and increased Lee index compared with the H rats. Training decreased the body weight and Lee index of the MS rats (MS-T vs. MS), but not of the H rats (H-T vs. H). There were no differences in food intake between the groups. At the end of the experiments, the systolic blood pressure was lower in the two trained groups than in their sedentary controls. Whole-body insulin sensitivity increased in the trained groups. Glucose transporter Type 4 content increased in the heart, white adipose tissue and gastrocnemius muscle of the trained groups relative to their respective untrained groups. CONCLUSION: In conclusion, the present study shows that an isolated aerobic exercise training intervention is an efficient means of improving several components of metabolic syndrome, that is, training reduces obesity and hypertension and increases insulin sensitivity

Norm and difference : Stone Age dietary practice in the Baltic region

Stone Age research on Northern Europe frequently makes gross generalizations about the Mesolithic and Neolithic, although we still lack much basic knowledge on how the people lived. The transition from the Mesolithic to the Neolithic in Europe has been described as a radical shift from an economy dominated by marine resources to one solely dependent on farming. Both the occurrence and the geographical extent of such a drastic shift can be questioned, however. It is therefore important to start out at a more detailed level of evidence in order to present the overall picture, and to account for the variability even in such regional or chronological overviews. Fifteen Stone Age sites were included in this study, ranging chronologically from the Early Mesolithic to the Middle or Late Neolithic, c. 8300–2500 BC, and stretching geographically from the westernmost coast of Sweden to the easternmost part of Latvia within the confines of latitudes 55–59° N. The most prominent sites in terms of the number of human and faunal samples analysed are Zvejnieki, Västerbjers and Skateholm I–II. Human and faunal skeletal remains were subjected to stable carbon and nitrogen isotope analysis to study diet and ecology at the sites. Stable isotope analyses of human remains provide quantitative information on the relative importance of various food sources, an important addition to the qualitative data supplied by certain artefacts and structures or by faunal or botanical remains. A vast number of new radiocarbon dates were also obtained. In conclusion, a rich diversity in Stone Age dietary practice in the Baltic Region was demonstrated. Evidence ranging from the Early Mesolithic to the Late Neolithic show that neither chronology nor location alone can account for this variety, but that there are inevitably cultural factors as well. Food habits are culturally governed, and therefore we cannot automatically assume that people at similar sites will have the same diet. Stable isotope studies are very important here, since they tell us what people actually consumed, not only what was available, or what one single meal contained. We should not be deceived in inferring diet from ritually deposited remains, since things that were mentally important were not always important in daily life. Thus, although a ritual and symbolic norm may emphasize certain food categories, these may in fact contribute very little to the diet. By the progress of analysis of intra-individual variation, new data on life history changes have been produced, revealing mobility patterns, breastfeeding behaviour and certain dietary transitions. The inclusion of faunal data has proved invaluable for understanding the stable isotope ecology of a site, and thereby improve the precision of the interpretations of human stable isotope data. The special case of dogs, though, demonstrates that these animals are not useful for inferring human diet, since, due to the number of roles they possess in human society, dogs could deviate significantly from humans in their diet, and in several cases have been proved to do so. When evaluating radiocarbon data derived from human and animal remains from the Pitted-Ware site of Västerbjers on Gotland, the importance of establishing the stable isotope ecology of the site before making deductions on reservoir effects was further demonstrated. The main aim of this thesis has been to demonstrate the variation and diversity in human practices, challenging the view of a “monolithic” Stone Age. By looking at individuals and not only at populations, the whole range of human behaviour has been accounted for, also revealing discrepancies between norm and practice, which are frequently visible both in the archaeological record and in present-day human behaviour.

Importance of the proportions of dietary polyunsaturated fatty acids and antioxoidants in larval development of marine fish

La acuicultura es uno de los sectores con mayor crecimiento en la producción animal mundial, con una tasa superior al 5% anual en la última década (Izquierdo et al., 2008). En la acuicultura, el éxito del cultivo de cualquier especie de peces marinos está limitado por la cantidad y la calidad de la producción en masa de sus alevines (Izquierdo y Fernández - Palacios, 1997). Por lo tanto, para cubrir las crecientes demandas de la producción de semillas, es necesario mejorar la calidad nutritiva de sus larvas, lo cual todavía constituye una de las principales limitaciones para el desarrollo del cultivo de especies de peces marinos (Watanabe et al., 1983; Yúfera y Pascual, 1984; Sargent et al. 1997; Izquierdo et al., 2000). Aunque la producción Mediterránea del cultivo de peces marinos se ha incrementado en varias especies, la dorada Sparus aurata continúa siendo la especie mas cultivada (Izquierdo, 2005), con una producción anual de alevines que supera los 120 millones/ año. La demanda de alevines de buena calidad está aumentando a un ritmo del 10% anual, pero el éxito de la producción de los juveniles se ve muy afectado por la eficacia de la primera alimentación y la calidad nutricional de la dieta de arranque (Kolkovski et al., 1993; Sargent et al., 1997; Izquierdo et al., 2000). En general, la dorada y la lubina europea (Dicentrarchus labrax) son las especies más importantes de peces marinos criados en la región mediterránea y han caracterizado el desarrollo de la acuicultura marina en esta región en las últimas tres décadas (FAO, 1999). Además, en la producción, de ambas especies, se prevee una mayor expansión (Basurco y Abellán, 1999). Sin embargo, a pesar de que el engorde de estas especies está bien controlado, el conocimiento de sus necesidades nutricionales, en comparación con otras especies como salmónidos y carpas, sigue siendo incompleto (NRC, 1993). Por lo tanto, para obtener un mejor crecimiento y una mayor tasa de supervivencia, es esencial una dieta que responda a las necesidades nutricionales de las larvas, tanto cualitativas como cuantitativas (Kolkovski et al., 1993; Sargent et al., 1997). Además, incluso antes de que comience el desarrollo larvario, los huevos de los peces deben contener todos los nutrientes que cubran los requerimientos adecuados para el desarrollo del embrión (Izquierdo y Fernández - Palacios, 1997). En los últimos años, las investigaciones han prestado gran atención a la importancia de los lípidos dietéticos para larvas de peces marinos (Izquierdo et al., 2003), puesto que son esenciales para el crecimiento y el desarrollo de los mismos (Watanabe, 1982; Sargent et al., 1999a). Como reflejo de esta importancia, la dieta para dorada y lubina se ha convertido en una dieta altamente energética (25% de lípidos) en comparación con la década anterior (12% de lípidos) (Izquierdo et al., 2003). Los lípidos dietéticos proporcionan una fuente rica de energía y fosfolípidos y son fundamentales para la estructura de las biomembranas. Los lípidos dietéticos también sirven como vehículos para la absorción de otros nutrientes, como las vitaminas liposolubles A, D, E, y K, y pigmentos naturales o sintéticos. Los lípidos son componentes de las hormonas y precursores para la síntesis de diversos metabolitos funcionales, como las prostaglandinas y otros eicosonoides. Además, los lípidos dietéticos son reconocidos como uno de los factores nutricionales más importantes que afectan el crecimiento y la supervivencia de las larvas (Watanabe et al., 1983), porque constituyen materiales esenciales para la formación normal de célula, las membranas de los tejidos y el desarrollo de órganos (Izquierdo et al., 1998, 2003; Pousaò et al., 2003). Sin embargo, la utilización de los lípidos dietéticos por las larvas puede verse afectada directa o indirectamente por varios cambios morfológicos y fisiológicos que ocurren durante el desarrollo larvario. En los últimos años ha habido más interés en todos estos aspectos nutricionales de los lípidos en las larvas de peces, debido a la importancia de utilización de los lípidos dieteticos para el óptimo crecimiento y supervivencia larvaria (Izquierdo et al., 2000).