High Iodine Concentration Attenuates RET/PTC3 Oncogene Activation in Thyroid Follicular Cells

Background: Papillary thyroid carcinoma (PTC) is frequently associated with a RET gene rearrangement that generates a RET/PTC oncogene. RET/PTC is a fusion of the tyrosine kinase domain of RET to the 50 portion of a different gene. This fusion results in a constitutively active MAPK pathway, which plays a key role in PTC development. The RET/PTC3 fusion is primarily associated with radiation-related PTC. Epidemiological studies show a lower incidence of PTC in radiation-exposed regions that are associated with an iodine-rich diet. Since the influence of excess iodine on the development of thyroid cancer is still unclear, the aim of this study is to evaluate the effect of high iodine concentrations on RET/PTC3-activated thyroid cells. Methods: PTC3-5 cells, a rat thyroid cell lineage harboring doxycycline-inducible RET/PTC3, were treated with 10(-3) M NaI. Cell growth was analyzed by cell counting and the MTT assay. The expression and phosphorylation state of MAPK pathway-related (Braf, Erk, pErk, and pRet) and thyroid-specific (natrium-iodide symporter [Nis] and thyroid-stimulating hormone receptor [Tshr]) proteins were analyzed by Western blotting. Thyroid-specific gene expression was further analyzed by quantitative reverse transcription (RT)-polymerase chain reaction. Results: A significant inhibition of proliferation was observed, along with no significant variation in cell death rate, in the iodine-treated cells. Further, iodine treatment attenuated the loss of Nis and Tshr gene and protein expression induced by RET/PTC3 oncogene induction. Finally, iodine treatment reduced Ret and Erk phosphorylation, without altering Braf and Erk expression. Conclusion: Our results indicate an antioncogenic role for excess iodine during thyroid oncogenic activation. These findings contribute to a better understanding of the effect of iodine on thyroid follicular cells, particularly how it may play a protective role during RET/PTC3 oncogene activation.

Pollen substitutes increase honey bee haemolymph protein levels as much as or more than does pollen

Adequate substitutes for pollen are necessary for maintaining healthy bee colonies during periods of pollen dearth, but testing them objectively is both time consuming and expensive. We compared two commercial diets with bee collected pollen and acacia pod flour (used by beekeepers in some parts of Brazil) by measuring their effect on haemolymph protein contents of young bees exclusively fed on these diets, which is a fast and inexpensive assay. The commercial diets included a new, non-soy-based, pollen substitute diet (named Feed-Bee (R)) and a soy-based diet, named Bee-Pro (R). The diets were each given in patty form to groups of 100 Africanized honey bees in hoarding cages, maintained and fed from emergence until six days of age. Sucrose, in the form of sugar syrup, was used as a protein free control. Feed-Bee (R), Bee-Pro (R), pollen and acacia pod flour diets increased protein titers in the haemolymph by factors of 2.65, 2.51, 1.76 and 1.69, respectively, over protein titers in bees fed only sucrose solution. The bees fed Feed-Bee (R) and Bee-Pro (R) had their haemolymph significantly enriched in protein compared to the controls and those fed acacia pod flour and to titers slightly higher than those fed pollen. All four proteinaceous diets were significantly superior to sucrose alone.

The ecological basis of life history variation in marsupials

Our understanding of the diversity of mammalian life histories is based almost exclusively on eutherian mammals, in which the slow-fast continuum persists even after controlling for effects of body size and phylogeny. In this paper, we use modern comparative methods to test the extent to which this eutherian-based framework can be extrapolated to metatherian mammals. First, we examine the pattern of covariation among life history traits, and second, we test for correlations between variation in life history and variation in six candidate ecological variables: type of diet, extent of intraspecific competition, risk of juvenile mortality, diurnal pattern of activity, arboreality, and rainfall pattern. Even when controlling for body size and phylogeny, we observe a slow-fast continuum in metatherian mammals. Some parameters involved are different from those identified by studies of eutherians, but the underlying relationships among longevity, fecundity, and age at maturity persist. We also show that overall variation in a key life history variable, reproductive output (measured by annual reproductive rate and litter size), is significantly related to variation in type of diet, with a foliage-rich diet being associated with low fecundity. This is interesting because, although ecological correlations have been found within some eutherian subgroups, modern comparative approaches have failed to reveal robust ecological correlates of overall life history diversity in eutherians. Copyright ESA. All rights reserved.

Determinação de germânio em alimentos por espectrometria de massa ligada a um plasma acoplada indutivamente (ICP-MS)

Nos dias de hoje existe uma grande preocupação da população em fazer uma alimentação mais saudável, uma alimentação que tenha nos seus alimentos elementos que não prejudiquem a saúde mas sim que a tornem mais forte. Um desses elementos que pode trazer benefício para a saúde é o Germânio, elemento de estudo no presente trabalho. Neste trabalho determinou-se a concentração de Germânio em alguns alimentos. Os alimentos usados foram: espargos, ginseng, cogumelos, rabanete, gengibre, aloé vera e alho. Para se fazer a decomposição das amostras foi usada uma solução de ácido nítrico concentrado (67%) e peróxido de hidrogénio (30%), de seguida as soluções resultantes foram analisadas por espectrometria de massa ligado a um plasma acoplado indutivamente (Inductive Coupled Plasma - Mass Spectrometry (ICP-MS)). Esta técnica permitiu estudar os três isótopos mais abundantes de germânio (Ge70, Ge72 e Ge74). Como principais resultados deste trabalho pode-se referir que o alimento que apresenta uma maior concentração de Germânio é o ginseng (243,0 ng/g), seguindo-se o alho (152,6 ng/g). Com concentrações bastante próximas ficaram os espargos, gengibre e cogumelos com um valor aproximado de 75 ng/g. As concentrações mais baixas formam encontradas no aloé vera e rabanete, com valores de 38,16 e 21,85ng/g respectivamente. Com estes resultados podemos concluir que para ter uma alimentação rica neste elemento deve-se ingerir ginseng e alho pois dos alimentos estudados são os mais ricos em Germânio.

Neural Mechanisms of Exercise: Effects on Gut Miccrobiota and Depression

Microbiota is a set of microorganisms resident in gut ecosystem that reacts to psychological stressful stimuli, and is involved in depressed or anxious status in both animals and human being. Interestingly, a series of studies have shown the effects of physical exercise on gut microbiota dynamics, suggesting that gut microbiota regulation might act as one mediator for the effects of exercise on the brain. Recent studies found that gut microbiota dynamics are also regulated by metabolism changes, such as through physical exercise or diet change. Interestingly, physical exercise modulates different population of gut bacteria in compared to food restriction or rich diet, and alleviates gut syndromes to toxin intake. Gut microbiota could as well contribute to the beneficial effects of exercise on cognition and emotion, either directly through serotonin signaling or indirectly by modulating metabolism and exercise performance.

A growth hormone-releasing peptide that binds scavenger receptor CD36 and ghrelin receptor up-regulates sterol transporters and cholesterol efflux in macrophages through a peroxisome proliferator-activated receptor gamma-dependent pathway.

Macrophages play a central role in the pathogenesis of atherosclerosis by accumulating cholesterol through increased uptake of oxidized low-density lipoproteins by scavenger receptor CD36, leading to foam cell formation. Here we demonstrate the ability of hexarelin, a GH-releasing peptide, to enhance the expression of ATP-binding cassette A1 and G1 transporters and cholesterol efflux in macrophages. These effects were associated with a transcriptional activation of nuclear receptor peroxisome proliferator-activated receptor (PPAR)gamma in response to binding of hexarelin to CD36 and GH secretagogue-receptor 1a, the receptor for ghrelin. The hormone binding domain was not required to mediate PPARgamma activation by hexarelin, and phosphorylation of PPARgamma was increased in THP-1 macrophages treated with hexarelin, suggesting that the response to hexarelin may involve PPARgamma activation function-1 activity. However, the activation of PPARgamma by hexarelin did not lead to an increase in CD36 expression, as opposed to liver X receptor (LXR)alpha, suggesting a differential regulation of PPARgamma-targeted genes in response to hexarelin. Chromatin immunoprecipitation assays showed that, in contrast to a PPARgamma agonist, the occupancy of the CD36 promoter by PPARgamma was not increased in THP-1 macrophages treated with hexarelin, whereas the LXRalpha promoter was strongly occupied by PPARgamma in the same conditions. Treatment of apolipoprotein E-null mice maintained on a lipid-rich diet with hexarelin resulted in a significant reduction in atherosclerotic lesions, concomitant with an enhanced expression of PPARgamma and LXRalpha target genes in peritoneal macrophages. The response was strongly impaired in PPARgamma(+/-) macrophages, indicating that PPARgamma was required to mediate the effect of hexarelin. These findings provide a novel mechanism by which the beneficial regulation of PPARgamma and cholesterol metabolism in macrophages could be regulated by CD36 and ghrelin receptor downstream effects.

Molecular role of Cx37 in advanced atherosclerosis: a micro-array study.

Recently, we showed that connexin37 (Cx37) protects against early atherosclerotic lesion development by regulating monocyte adhesion. The expression of this gap junction protein is altered in mouse and human atherosclerotic lesions; it is increased in macrophages newly recruited to the lesions and disappears from the endothelium of advanced plaques. To obtain more insight into the molecular role of Cx37 in advanced atherosclerosis, we used micro-array analysis for gene expression profiling in aortas of ApoE(-/-) and Cx37(-/-)ApoE(-/-) mice before and after 18 weeks of cholesterol-rich diet. Out of >15,000 genes, 106 genes were significantly differentially expressed in young mice before diet (P-value of <0.05, fold change of >0.7 or <-0.7, and intensity value >2.2 times background). Ingenuity pathway analysis (IPA) revealed differences in genes involved in cell-to-cell signaling and interaction, cellular compromise and nutritional disease. In addition, we identified 100 genes that were significantly perturbed after the cholesterol-rich diet. Similar to the analysis on 10-week-old mice, IPA revealed differences in genes involved in cell-to-cell signaling and interaction as well as to immuno-inflammatory disease. Furthermore, we found important changes in genes involved in vascular calcification and matrix degradation, some of which were confirmed at protein level by (immuno-)histochemistry. In conclusion, we suggest that Cx37 deficiency alters the global differential gene expression profiles in young mice towards a pro-inflammatory phenotype, which are then further influenced in advanced atherosclerosis. The results provide new insights into the significance of Cx37 in plaque calcification.

Dietary restriction affects lifespan but not cognitive aging in Drosophila melanogaster.

Summary Dietary restriction extends lifespan in a wide variety of animals, including Drosophila, but its relationship to functional and cognitive aging is unclear. Here, we study the effects of dietary yeast content on fly performance in an aversive learning task (association between odor and mechanical shock). Learning performance declined at old age, but 50-day-old dietary-restricted flies learned as poorly as equal-aged flies maintained on yeast-rich diet, even though the former lived on average 9 days (14%) longer. Furthermore, at the middle age of 21 days, flies on low-yeast diets showed poorer short-term (5 min) memory than flies on rich diet. In contrast, dietary restriction enhanced 60-min memory of young (5 days old) flies. Thus, while dietary restriction had complex effects on learning performance in young to middle-aged flies, it did not attenuate aging-related decline of aversive learning performance. These results are consistent with the hypothesis that, in Drosophila, dietary restriction reduces mortality and thus leads to lifespan extension, but does not affect the rate with which somatic damage relevant for cognitive performance accumulates with age.

Response of hexokinase enzymes and the insulin system to dietary carbohydrates in the common carp, Cyprinus carpio.

The response of the common carp to diets with varying amounts of digestible starch, provided either as pea meal (LP, HP, 30 and 46% peas, respectively) or as cereal (LW, HW, 30 and 46% wheat, respectively), was studied and compared with the response to a carbohydrate-free protein-rich diet (CF). Here we focused on the utilisation of dietary carbohydrates by examining the relationship between dietary starch intake, hepatic hexokinase activities, circulating insulin and muscle insulin receptor system. Plasma glucose concentration and hepatic high Km hexokinase (glucokinase, GK) activity were not affected by the content of digestible starch, but 6 h after feeding enzyme activity was higher in the fish fed carbohydrate diets. Similarly, low Km hexokinase (HK) activity was also higher in the fish 24 h after feeding. Fat gain and protein retention were significantly improved by increased digestible starch intake, especially in the HP group, which in turn, presented the highest plasma insulin levels. Glycogen stores were moderately increased by the ingestion of digestible starch. The number of insulin receptors was greater in the CF group than in fish on carbohydrates, except the HP group. Our results confirmed that the common carp uses dietary carbohydrates efficiently, especially when there are provided by peas. This efficiency might be related to the enhanced response of postprandial insulin observed in the HP group.

Monounsaturated fats and immune function

Animal studies suggest that olive oil is capable of modulating functions of cells of the immune system in a manner similar to, albeit weaker than, fish oils. There is some evidence that the effects of olive oil on immune function in animal studies are due to oleic acid rather than to trace elements or antioxidants. Importantly, several studies have demonstrated effects of oleic acid-containing diets on in vivo immune responses. In contrast, consumption of a monounsaturated fatty acid (MUFA)-rich diet by humans does not appear to bring about a general suppression of immune cell functions. The effects of this diet in humans are limited to decreasing aspects of adhesion of peripheral blood mononuclear cells, although there are trends towards decreases in natural killer cell activity and proliferation. The lack of a clear effect of MUFA in humans may be attributable to the higher level of monounsaturated fat used in the animal studies, although it is ultimately of importance to examine the effects of intakes which are in no way extreme. The effects of MUFA on adhesion molecules are potentially important, since these molecules appear to have a role in the pathology of a number of diseases involving the immune system. This area clearly deserves further exploration

Protective effect of policosanol on atherosclerotic lesions in rabbits with exogenous hypercholesterolemia

Policosanol is a mixture of higher aliphatic alcohols purified from sugar cane wax, with cholesterol-lowering effects demonstrable in experimental models and in patients with type II hypercholesterolemia. The protective effects of policosanol on atherosclerotic lesions experimentally induced by lipofundin in rabbits and rats and spontaneously developed in stumptail monkeys have been described. The present study was conducted to determine whether policosanol administered orally to rabbits with exogenous hypercholesterolemia also protects against the development of atherosclerotic lesions. Male New Zealand rabbits weighing 1.5 to 2 kg were randomly divided into three experimental groups which received 25 or 200 mg/kg policosanol (N = 7) orally for 60 days with acacia gum as vehicle or acacia gum alone (control group, N = 9). All animals received a cholesterol-rich diet (0.5%) during the entire period. Control animals developed marked hypercholesterolemia, macroscopic lesions and arterial intimal thickening. Intima thickness was significantly less (32.5 ± 7 and 25.4 ± 4 µm) in hypercholesterolemic rabbits treated with policosanol than in controls (57.6 ± 9 µm). In most policosanol-treated animals, atherosclerotic lesions were not present, and in others, thickness of fatty streaks had less foam cell layers than in controls. We conclude that policosanol has a protective effect on the atherosclerotic lesions occurring in this experimental model.

Incorporation of dietary trans monounsaturated fatty acids into tissues of Walker 256 tumor-bearing rats

The correlation between dietary trans fatty acids and neoplasia was examined in the present study. Walker 256 tumor-bearing and control rats were fed a trans monounsaturated fatty acid (MUFA)-rich diet for 8 weeks and the incorporation of trans fatty acids by tumor tissue was examined. Also, the effect of tumor growth on trans fatty acid composition of plasma and liver, and the content of thiobarbituric acid-reactive substances (TBARS) was determined. Walker 256 tumor cells presented both trans and cis MUFAs given in the diet. The equivalent diet proportions were 0.66 for trans and 1.14 for cis. Taking into consideration the proportion of trans MUFAs in plasma (11.47%), the tumor incorporated these fatty acids in a more efficient manner (18.27%) than the liver (9.34%). Therefore, the dietary trans fatty acids present in the diet are actively incorporated by the tumor. Tumor growth itself caused marked changes in the proportion of polyunsaturated fatty acids in the plasma and liver but provoked only slight modifications in both trans and cis MUFAs. Tumor growth also reduced the unsaturation index in both plasma and liver, from 97.79 to 86.83 and from 77.51 to 69.64, respectively. This effect was partially related to an increase in the occurrence of the lipid oxidation/peroxidation process of TBARS content which was increased in both plasma (from 0.428 to 0.505) and liver (from 9.425 to 127.792) due to tumor growth.

Effect of sexual steroids on the calcium content of aortic atherosclerotic plaque of oophorectomized rabbits

We determined the effect of conjugated equine estrogen plus medroxyprogesterone acetate on calcium content of aortic atherosclerotic lesions in oophorectomized adult New Zealand rabbits submitted to a cholesterol rich diet. Five groups of 10 animals each were studied: G1 = control, G2 = cholesterol diet only, G3 = diet plus conjugated equine estrogen (0.625 mg/day); G4 and G5 = diet, conjugated equine estrogen (0.625 mg/day) plus medroxyprogesterone acetate (5 and 10 mg/day, respectively). Mean weight varied from 2.7 ± 0.27 to 3.1 ± 0.20 kg (P = 0.38) between groups at the beginning and 3.1 ± 0.27 to 3.5 ± 0.20 kg (P = 0.35) at the end of the experiment. Cholesterol and triglyceride levels were determined at the time of oophorectomy, 21 days after surgery (time 0), and at the end of follow-up of 90 days. The planimetric method was used to measure plaque and caryometric method for histopathologic examination of the aorta. Calcium content was determined by the method of von Kossa. A similar increase in cholesterol occurred in all treated groups without differences between them at the end of the study. Groups G4 and G5 had smaller areas of atherosclerotic lesions (2.33 ± 2.8 and 2.45 ± 2.1 cm², respectively) than the groups receiving no progestogens (G2: 5.6 ± 4 and G3: 4.6 ± 2.8 cm²; P = 0.02). The relation between lesion area and total aorta area was smaller in groups treated with combined drugs compared to the groups receiving no progesterone (G4: 14.9 ± 13 and G5: 14.2 ± 13.4 vs G2: 35.8 ± 26 and G3: 25 ± 8 cm², respectively; P = 0.017). Oral conjugated equine estrogen (0.625 mg/day) plus medroxyprogesterone acetate (5 or 10 mg/day) provoked a greater reduction in atherosclerotic plaque area and calcium content in treated groups, suggesting a dose-dependent effect.

Effect of unsaturated fatty acids on myocardial performance, metabolism and morphology

Diets rich in saturated fatty acids are one of the most important causes of atherosclerosis in men, and have been replaced with diets rich in unsaturated fatty acids (UFA) for the prevention of this disorder. However, the effect of UFA on myocardial performance, metabolism and morphology has not been completely characterized. The objective of the present investigation was to evaluate the effects of a UFA-rich diet on cardiac muscle function, oxidative stress, and morphology. Sixty-day-old male Wistar rats were fed a control (N = 8) or a UFA-rich diet (N = 8) for 60 days. Myocardial performance was studied in isolated papillary muscle by isometric and isotonic contractions under basal conditions after calcium chloride (5.2 mM) and ß-adrenergic stimulation with 1.0 µM isoproterenol. Fragments of the left ventricle free wall were used to study oxidative stress and were analyzed by light microscopy, and the myocardial ultrastructure was examined in left ventricle papillary muscle. After 60 days the UFA-rich diet did not change myocardial function. However, it caused high lipid hydroperoxide (176 ± 5 vs 158 ± 5, P < 0.0005) and low catalase (7 ± 1 vs 9 ± 1, P < 0.005) and superoxide-dismutase (18 ± 2 vs 27 ± 5, P < 0.005) levels, and discrete morphological changes in UFA-rich diet hearts such as lipid deposits and mitochondrial membrane alterations compared to control rats. These data show that a UFA-rich diet caused myocardial oxidative stress and mild structural alterations, but did not change mechanical function.

Not any type of rice performs equally to improve lactose-induced diarrhea characteristics in rats: is amylose an antidiarrheal factor?

The effectiveness of different types of rice in relation to their ability to accelerate diarrhea recovering was evaluated in a rat model of osmotic diarrhea (OD). Animals (90-100 g) received protein free diet until reaching up to 20% weight loss, followed by lactose rich diet (LRD) to induce osmotic diarrhea. Rats presenting osmotic diarrhea were divided into 4 groups, which received lactose rich diet for 4 days from 8 am to 8 pm, and one of three experimental products containing 6% rice flour differing in amylose content during the night: high (HA), intermediate (IA), and low (LA). A group fed stock diet containing equivalent amount of lactose was taken as control and allowed to recover spontaneously. Amylose and viscosity (cp at 25 °C, 10 rpm) of final products were determined. Effectiveness was expressed as the ratio between percentages of normal vs. diarrheic stools during the treatment. Fecal characteristics in this rat model improved only as result of feeding high amylose content (HA) type of rice. In this experimental model of osmotic diarrhea in young rats, the antidiarrheal effects of rice were strongly dependent on the type of diet used and appear to be related to its amylose content.