Effects of high-fat diet on somatic growth, metabolic parameters and function of peritoneal macrophages of young rats submitted to a maternal low-protein diet.

This study evaluated the effects of a post-weaning high-fat (HF) diet on somatic growth, food consumption, metabolic parameters, phagocytic rate and nitric oxide (NO) production of peritoneal macrophages in young rats submitted to a maternal low-protein (LP) diet. Male Wistar rats (aged 60 d) were divided in two groups (n 22/each) according to their maternal diet during gestation and lactation: control (C, dams fed 17 % casein) and LP (dams fed 8 % casein). At weaning, half of the groups were fed HF diet and two more groups were formed (HF and low protein-high fat (LP-HF)). Somatic growth, food and energy intake, fat depots, serum glucose, cholesterol and leptin concentrations were evaluated. Phagocytic rate and NO production were analysed in peritoneal macrophages under stimulation of zymosan and lipopolysaccharide (LPS)+interferon γ (IFN-γ), respectively. The maternal LP diet altered the somatic parameters of growth and development of pups. LP and LP-HF pups showed a higher body weight gain and food intake than C pups. HF and LP-HF pups showed increased retroperitoneal and epididymal fat depots, serum level of TAG and total cholesterol compared with C and LP pups. After LPS+IFN-γ stimulation, LP and LP-HF pups showed reduced NO production when compared with their pairs. Increased phagocytic activity and NO production were seen in LP but not LP-HF peritoneal macrophages. However, peritoneal macrophages of LP pups were hyporesponsive to LPS+IFN-γ induced NO release, even after a post-weaning HF diet. Our data demonstrated that there was an immunomodulation related to dietary fatty acids after the maternal LP diet-induced metabolic programming.

Moderate physical training attenuates perinatal low-protein-induced spleen lymphocyte apoptosis in endotoxemic adult offspring rats.

PURPOSE: To evaluate the effects of a moderate physical training (T) on the blood and splenic lymphocytes subsets and the rate of apoptosis in adult offspring submitted to perinatal low-protein (LP) diet. METHODS: Male Wistar rats were divided according to their mother's diet: control (C, 17 % casein) and undernourished (LP, 8 % casein). At the 60th day, pups were submitted to moderate physical training (8 weeks, 5 days week(-1), 60 min day(-1), at 70 % of VO2max). After T period, pups received an injection of lipopolysaccharide (LPS). B, NK, and TCD3+ lymphocytes subsets were analyzed by flow cytometry. Spleen lymphocytes apoptosis was evaluated by DNA fragmentation, phosphatidylserine externalization (PSE), and mitochondrial transmembrane depolarization (MTD) using a flow cytometer. Plasma TNF-α concentrations were analyzed by ELISA. RESULTS: LP + LPS pups showed a higher percentage of blood B, CD4+, and NK and a reduction in TCD3+, CD8+ than C pups. The percentage of NK and CD3+ was restored in LP + T + LPS pups. In the spleen, T normalized the percentage of NK in LP + LPS pups. LP + LPS pups showed a higher percentage of cells with PSE and MTD than C + LPS pups that was attenuated by T. The concentration of TNF-α was higher in LP + LPS than C + LPS, but it was attenuated in LP + T + LPS pups. CONCLUSION: Moderate physical training was able to revert the effects of perinatal LP diet on circulation lymphocytes subsets and attenuated splenic lymphocytes apoptosis and plasma TNF-α concentrations.

LipoCardium: endothelium-directed cyclopentenone prostaglandin-based liposome formulation that completely reverses atherosclerotic lesions.

Atherosclerosis is a multifactorial inflammatory disease of blood vessels which decimates one in every three people in industrialized world. Despite the important newest clinical approaches, currently available strategies (e.g. nutritional, pharmacological and surgical) may only restrain the worsening of vascular disease. Since antiproliferative cyclopentenone prostaglandins (CP-PGs) are powerful anti-inflammatory agents, we developed a negatively charged liposome-based pharmaceutical formulation (LipoCardium) that specifically direct CP-PGs towards the injured arterial wall cells of atherosclerotic mice. In the blood stream, LipoCardium delivers its CP-PG contents only into activated arterial wall lining cells due to the presence of antibodies raised against vascular cell adhesion molecule-1 (VCAM-1), which is strongly expressed upon inflammation by endothelial cells and macrophage-foam cells as well. After 4 months in a high-lipid diet, all low-density lipoprotein receptor-deficient adult control mice died from myocardium infarction or stroke in less than 2 weeks, whereas LipoCardium-treated (2 weeks) animals (still under high-lipid diet) completely recovered from vascular injuries. In vitro studies using macrophage-foam cells suggested a tetravalent pattern for LipoCardium action: anti-inflammatory, antiproliferative (and pro-apoptotic only to foam cells), antilipogenic and cytoprotector (via heat-shock protein induction). These astonishing cellular effects were accompanied by a marked reduction in arterial wall thickness, neointimal hyperplasia and lipid accumulation, while guaranteed lifespan to be extended to the elderly age. Our findings suggest that LipoCardium may be safely tested in humans in a near future and may have conceptual implications in atherosclerosis therapy.

PERINATAL MALNUTRITION AND THE PROTECTIVE ROLE OF THE PHYSICAL TRAINING ON THE IMMUNE SYSTEM.

Developing organisms have the ability to cope with environmental demands through physiologic and morphologic adaptations. Early life malnutrition has been recognized as an environmental stimulus that is related with down-regulation of immune responses. Some of these effects are explained by the epigenetics and the programming of hormones and cytokines impairing the modulation of the immune cells in response to environmental stimuli. Recently, it has been demonstrated that these effects are not deterministic and current environment, such as physical activity, can positively influence the immune system. Here, we discuss the effects of perinatal malnutrition on the immune system and how it can be modulated by physical training. The mechanism includes the normalization of some hormones concentrations related to growth and metabolism such as leptin, IGF-1 and glucocorticoids.

Los organismos en desarrollo tienen la capacidad de hacer frente a las demandas ambientales a través de adaptaciones fisiológicas y morfológicas. la malnutrición perinatal ha sido reconocida como un estímulo ambiental que está relacionado con la baja regulación de la respuesta inmune. Algunos de estos efectos se explican por la epigenética y la programación de las hormonas y citoquinas que son responsables de la modulación de las células inmunes en respuesta a los estímulos ambientales. Recientemente se ha demostrado que estos efectos no son deterministas y que la actividad física puede influir positivamente en el sistema inmunológico. Aquí se discuten los efectos de la desnutrición perinatal sobre el sistema inmune y cómo puede ser modulada por el entrenamiento físico. El mecanismo incluye la normalización de las concentraciones de algunas hormonas relacionadas con el crecimiento y el metabolismo tales como la leptina, IGF-1 y los glucocorticoides.

Effect of flower essence therapy on teachers' stress: a randomized clinical trial / Efeito da terapia floral no estresse docente: ensaio clínico randomizado / Efecto de la terapia floral en el estrés docente: ensayo clínico aleatorizado

RESUMO Objetivo: avaliar a efetividade das essências florais de Bach na redução dos níveis de estresse docente. Método: ensaio clínico controlado, randomizado, duplo-cego, com delineamento prospectivo. Foram utilizados na coleta de dados um formulário validado à luz da teoria de Betty Neuman e três instrumentos, um na perspectiva perceptiva (PSS-14), o outro na prevalência dos sinais e sintomas (LSS) e um de avaliação dos aspectos bioeletrográfico (FAAB). A amostra foi constituída de 27 professores da rede básica de ensino com estresse médio e alto, distribuídos em dois grupos: intervenção (GI) e que recebeu floral e placebo (GP). Resultados: o GI mostrou-se efetivo na redução do estresse, sendo estatisticamente significante intragrupo com a diminuição das médias dos escores do PSS-14 (p=0,004, LSS - p = 0,000) e da bioeletrografia (p=0,011); bem como entre grupos com p-valor de 0,035 para LSS e FAAB com p= 0,001. Conclusão: as essências florais do sistema Bach mostraram-se efetivos no cuidado do estresse docente com a reestruturação da linha flexível de defesa, refletindo melhor relacionamento do professor com os estressores intra, inter e extrapessoais. Este estudo está registrado no ReBEC com o nº. UTN: U1111-1208-4987.

RESUMEN Objetivo: evaluar la efectividad de las esencias florales de Bach para reducir los niveles de estrés del personal docente. Método: ensayo clínico controlado, aleatorizado, doble ciego con diseño prospectivo. En la recogida de datos se utilizó un formulario validado a la luz de la teoría de Betty Neuman y tres instrumentos: uno en la perspectiva perceptiva (PSS-14), otro en la prevalencia de signos y síntomas (LSS) y otro para la evaluación de aspectos bioelectrográficos (FAAB) La muestra consistió en 27 profesores de educación básica con estrés medio y alto, divididos en dos grupos: intervención (GI), que recibió esencias florales, y placebo (GP). Resultados: el GI demostró ser efectivo para la reducción del estrés, siendo estadísticamente significativo dentro del grupo con disminución en las puntuaciones medias del PSS-14 (p = 0.004, LSS - p = 0.000) y bioelectrografía (p = 0.011); así como entre grupos con un valor de p de 0.035 para LSS y FAAB con p = 0.001. Conclusión: las Flores de Bach demostraron ser efectivas en el manejo del estrés de los docentes con la reestructuración de la línea flexible de defensa, reflejando una mejor relación entre el profesor y los estresores intra, inter y extrapersonales. El presente estudio está registrado en ReBEC bajo el nº. UTN: U1111-1208-4987.

ABSTRACT Objective: to evaluate the effectiveness of Bach flower essences in reducing teachers' stress levels. Method: a controlled, randomized, and double-blind clinical trial with a prospective design. In data collection, a form validated in the light of Betty Neuman's theory and another three instruments were used, one in the perceptive perspective (PSS-14), the second in the prevalence of the signs and symptoms (LSS), and the third for the evaluation of the bio-electrographic aspects (FAAB). The sample consisted of 27 teachers from the basic education network, with medium and high levels of stress and divided into two groups: intervention group (IG), the one that received Bach flower essences, and placebo group (PG). Results: the IG proved to be effective in reducing stress, being statistically significant intra-group with the decrease in the mean scores of PSS-14 (p=0.004), LSS (p=0.000), and bioelectrography (p=0.011); as well as between groups with a p-value of 0.035 for LSS, and FAAB with p=0.001. Conclusion: the Bach flower essences proved to be effective in the care of teachers' stress with the re-structuring of the flexible line of defense, reflecting in a better relationship between the teacher and intra-, inter-, and extra-personal stressors. This study is registered in the ReBEC under UTN Nº U1111-1208-4987.

Beneficial effect of glutamine on exercise-induced apoptosis of rat neutrophils.

INTRODUCTION/PURPOSE: The effect of a single bout of intensive exercise on apoptosis of rat neutrophils and the possible prevention by glutamine administration was examined. The experiments were performed in sexually immature and sexually mature male rats as to examine the possible involvement of sexual maturation in the effect of exercise. METHODS: Exercise was carried out on a treadmill for 1 h before rats were killed by decapitation. Aqueous solution of glutamine was given by gavage (1 g.kg-1 body weight), 1 h before exercise. Neutrophils were obtained by intraperitoneal lavage with phosphate-buffered saline (PBS), 4 h after injection of oyster glycogen solution. The cells were then analyzed for apoptosis by flow cytometry and fluorescence microscopy. Pro- and antiapoptotic gene expression was evaluated by reverse transcriptase chain reaction (RT-PCR). RESULTS: Neutrophils obtained from immature and mature exercised rats showed an increase in DNA fragmentation, chromatin condensation, and phosphatidylserine externalization. This suggests that all neutrophils suffered apoptosis. To study the possible mechanism involved, the production of reactive oxygen metabolites, expression of genes involved in apoptosis and mitochondrial transmembrane potential were examined. Acute exercise raised reactive oxygen metabolites production by neutrophils. Exercise did not change the expression of antiapoptotic (bcl-xL) and apoptotic (bax and bcl-xS) genes in neutrophils from immature rats but caused a significant increase of bax and bcl-xS expression and provoked a significant decrease of bcl-xL expression in cells from mature rats. Exercise also induced a marked loss of mitochondrial depolarization in neutrophils. Oral glutamine supplementation partially prevented the exercise-induced apoptosis in neutrophils from sexually immature and mature rats. CONCLUSION: The protective effect of glutamine on neutrophil apoptosis induced by acute exercise possibly occurs by preservation of mitochondrial function.

The effect of glutamine supplementation on the function of neutrophils from exercised rats.

In a recent publication, we showed the protective effect of glutamine on neutrophil apoptosis induced by acute exercise. The purpose of the present study was to examine the effect of a single bout of intensive exercise on rat neutrophil function and the possible effect of glutamine supplementation. An aqueous solution of glutamine was given by gavage (1 g per kg b.w.), 1 h before the exercise session. The exercise was carried out on a treadmill for 1 h at 85% VO2máx.. Neutrophils were obtained by intraperitoneal lavage with PBS. The following parameters were evaluated: phagocytosis capacity, production of nitric oxide and reactive oxygen metabolites, expression of iNOS, and expression of NADPH-oxidase components (p22phox, p47phox and gp91phox). One hour of exercise at 85% VO2max. induced no change in the phagocytosis capacity and reactive oxygen species production but decreased nitric oxide production. When rats received oral glutamine supplementation, the phagocytosis capacity was significantly increased, the decrease in nitric oxide production induced by exercise was abolished and production of reactive oxygen species was raised. Glutamine supplementation presents a significant effect on neutrophil function including changes induced by exercise.

Diabetes-induced alterations in latissimus dorsi muscle properties impair effectiveness of dynamic cardiomyoplasty in rats.

Short-term diabetes was induced in male Wistar rats with streptozotocin injection. The effects of diabetes on latissimus dorsi (LD) muscle contractile and biochemical properties and acute cardiomyoplasty (CDM) were assessed and compared with data from 16 control rats. Isometric force, contractile properties, and fatigue were measured in electrically stimulated muscles (0.3 ms, 1-256 Hz), and Na+K+ and Ca2+ATPase activities were quantified in muscle membrane preparations. Systolic arterial pressure and aortic blood flow were recorded at rest and during LD muscle stimulation. Compared with control muscle, diabetic muscle showed smaller maximum specific tetanic tension and lower rates of rise and fall in force. Diabetic LD muscle also showed lower muscle enzyme activities. Twitch tension and fatigue did not differ between groups. Smaller increases in aortic flow and systolic pressure after CDM were found in diabetic rats compared to controls. The marked decrease in CDM effectiveness in diabetic rats likely reflected the alterations in muscle properties associated with diabetes.

Função e apoptose do neutrófilo: modulação pela maturação sexual, exercício e suplementação com glutamina / Neutrophil function and apoptosis: modulation by sexual maturation, exercise and glutamine supplementation

O efeito de uma única sessão de exercício (a 85% da capacidade máxima) na função e apoptose de neutrófilos de ratos de 60 (imaturos sexualmente) e 90 (maduro sexualmente) dias foi estudado. Avaliou-se também o efeito da suplementação com glutamina (1g por kg de peso) na prevenção das alterações induzidas pelo exercício. As funções estudadas foram: capacidade fagocitária, produção de óxido nítrico (NO) e de espécies reativas de oxigênio (EROs). Para avaliar a morte de neutrófilos, os seguintes parâmetros foram determinados: integridade de membrana, condensação de cromatina, fragmentação de DNA, externalização de fosfatidilserina, potencial transmembrânico mitocondrial, expressão de genes anti-apoptóticos (bcl-xL), próapoptóticos (bax e bcl-xS) e caspase 3. A maturação sexual por si só reduziu a capacidade fagocitária, aumentou a expressão dos componentes (gp91, p47 e p22phox) da NADPH-oxidase e aumentou a produção de óxido nítrico (NO). Além disso, a maturação sexual aumentou a proporção de células em apoptose, conforme observado pelo aumento na fragmentação de DNA e despolarização mitocondrial, redução na expressão de Bcl-xL e aumento da expressão de caspase 3. A sessão de exercício, reduziu a produção de NO e aumentou a expressão dos componentes da NADPHoxidase nos neutrófilos de ratos de 90 dias. Em ratos de 60 dias, o exercício não alterou as funções dos neutrófilos (capacidade fagocitária, produção de óxido nítrico e de espécies reativas de oxigênio - EROs). A sessão de exercício aumentou a proporção de neutrófilos em apoptose em ratos de 60 e 90 dias. A suplementação oral com glutamina aumentou a capacidade fagocitária e a produção de EROs nos neutrófilos de ratos de 60 dias e a expressão dos componentes da NADPH-oxidase nos neutrófilos de ratos de 90 dias. Além disso, a suplementação com glutamina reduziu o efeito do exercício na indução de apoptose nos neutrófilos dos ratos de 60 e 90 dias.

The effect of a single session of intense exercise (85% maximal capacity) on apoptosis and function of neutrophils from 60 (sexually immature) and 90 (sexually mature) days-old rats was examined. The possible effect of glutamine supplementation (1 g per kg body weight) to prevent the changes induced by the exercise was also investigated. The functions studied were: phagocytic capacity, nitric oxide (NO) and reactive oxygen species (ROS) production. To evaluate the process of neutrophils death, the following parameters were determined: cell viability, chromatin condensation, DNA fragmentation, phosphatidylserine externalization, mitocondrial transmembrane potential, expression of anti-apoptotic (bcl-xL) and pro-apoptotic (bax, bcl-xS and caspase 3) genes. The sexual maturation per se decreased the phagocytic capacity, raised the expression of the NADPH-oxidase components (gp91, p47 and p22phox) and increased nitric oxide (NO) production. In addition, sexual maturation increased the proportion of cells in apoptosis as indicated by the increase in DNA fragmentation, mitochondrial depolarization and in caspase expression, and a reduction in bcl-xL expression. The exercise session decreased NO production and increased the expression of the NADPH-oxidase components in neutrophils from 90 days old rats. In 60 days old rats, the exercise did not affect neutrophil functions studied: phagocytic capacity, NO and reactive oxygen species (ROS) production. The exercise raised the proportion of neutrophils in apoptosis in both 60 and 90 days-old rats. Oral glutamine supplementation raised the phagocytic capacity and reactive oxygen species (ROS) production in neutrophils from 90 days old rats. In addition, glutamine supplementation decreased the effect of exercise on the induction of apoptosis in neutrophils from both 60 and 90 days old rats.