Profound hyperglycemia in knockout mutant mice identifies novel function for POU4F2/Brn-3b in regulating metabolic processes.

The POU4F2/Brn-3b transcription factor has been identified as a potentially novel regulator of key metabolic processes. Loss of this protein in Brn-3b knockout (KO) mice causes profound hyperglycemia and insulin resistance (IR), normally associated with type 2 diabetes (T2D), whereas Brn-3b is reduced in tissues taken from obese mice fed on high-fat diets (HFD), which also develop hyperglycemia and IR. Furthermore, studies in C2C12 myocytes show that Brn-3b mRNA and proteins are induced by glucose but inhibited by insulin, suggesting that this protein is itself highly regulated in responsive cells. Analysis of differential gene expression in skeletal muscle from Brn-3b KO mice showed changes in genes that are implicated in T2D such as increased glycogen synthase kinase-3β and reduced GLUT4 glucose transporter. The GLUT4 gene promoter contains multiple Brn-3b binding sites and is directly transactivated by this transcription factor in cotransfection assays, whereas chromatin immunoprecipitation assays confirm that Brn-3b binds to this promoter in vivo. In addition, correlation between GLUT4 and Brn-3b in KO tissues or in C2C12 cells strongly supports a close association between Brn-3b levels and GLUT4 expression. Since Brn-3b is regulated by metabolites and insulin, this may provide a mechanism for controlling key genes that are required for normal metabolic processes in insulin-responsive tissues and its loss may contribute to abnormal glucose uptake.

Feather mercury levels in seabirds at South Georgia: Influences of trophic position, sex and age

We studied the mercury contamination of 13 species of seabirds breeding on Bird Island, South Georgia, in 1998. Total mercury concentrations in body feather samples of birds caught at their breeding colonies were determined. Among the species, grey-headed albatross (8933 ng g-1) and southern giant petrel (7774 ng g-1) showed the highest, and gentoo penguin (948 ng g-1) the lowest body feather mercury concentrations. Mercury levels were negatively correlated with the proportion of crustaceans (mainly krill) in the species¹ diets, suggesting that the trophic level is the most important factor in explaining the variation of mercury concentrations in Antarctic seabirds. In 4 species studied for age effects among adult birds (grey-headed and black-browed albatross, northern and southern giant petrel), no age-dependent variation in mercury levels was found. Sex differences were also assessed: female gentoo penguins had lower mercury levels than males, which may be related to the elimination of part of the mercury body burden by females into eggs. In contrast, northern giant petrel males had lower levels than females, which may be related to a higher consumption by males of carrion from Antarctic fur seals. In grey-headed albatrosses, mercury levels were 113% higher than in 1989, when this species was investigated at the same site, indicating a possible increase in mercury pollution of the Southern Ocean during the last decade.

Effect of magnesium sulphate and L-tryptophan and genotype on the feed intake, behaviour and meat quality of pigs

Sixty-nine entire male pigs with different halothane genotype (homozygous halothanepositive – nn-, n=36; and homozygous halothane negative – NN-, n=33) were fed with a supplementation of magnesium sulphate (Mg) and/or L-tryptophan (Trp) in the diet for 5days before slaughter. Animals were housed individually and were submitted to stressful ante mortem conditions (mixed in the lorry according to treatments and transported 1h on rough roads). Individual feed intake was recorded during the 5-day treatment. At the abattoir, pig behaviour was assessed in the raceway to the stunning system and during the stunning period by exposure to CO2. Muscle pH, colour, water holding capacity, texture and cathepsin activities were determined to assess meat quality. The number of pigs with an individual feed intake lower than 2kg/day was significantly different among diets (P<0.05; Control: 8.7%; Mg&Trp: 43.5%; Trp:17.4%) and they were considered to have inadequate supplement intake. During the antemortem period, 15.2% of pigs included in the experiment died, and this percentagedecreased to 8.7% in those pigs with a feed intake > 2kg/day, all of them from thestress-sensitive pigs (nn). In general, no differences were observed in the behaviour ofpigs along the corridor leading to the stunning system and inside the CO2 stunningsystem. During the stunning procedure, Trp diet showed shorter periods of muscularexcitation than control and Mg&Trp diets. The combination of a stressful ante mortemtreatment and Mg&Trp supplementation led to carcasses with high incidence of severeskin lesions. Different meat quality results were found when considering all pigs orconsidering only those with adequate supplement intake. In this later case, Trp increased pH45 (6.15) vs Control diet (5.96) in the Longissimus thoracis (LT) muscle (P<0.05) and pH at 24h (Trp: 5.59 vs C: 5.47) led to a higher incidence of dark, firm and dry (DFD) traits in SM muscle (P<0.05). Genotype affected negatively all the meat quality traits. Seventy-five percent of LT and 60.0% of the SM muscles from nn pigs wereclassified as pale, soft and exudative (PSE), while none of the NN pigs showed these traits (P<0.0001). No significant differences were found between genotypes on the incidence of DFD meat. Due to the negative effects observed in the Mg&Trp group in feed intake and carcass quality, the utilization of a mixture of magnesium sulphate and tryptophan is not recommended

Effect of supplementation with MgCO3 and L-tryptophan on the welfare and on the carcass and meat quality of two halothane pig genotypes (NN and nn)

Sixty-one animals with different Halothane genes (homozygous halothane positive, n=34; and homozygous halothane negative, n=27) were fed with three diets (controlgroup, with no supplement; magnesium (Mg) group with 1.28g MgCO3/kg and tryptophan (Trp) group with 5g L-Trp/kg) during the last 5 days before slaughter. Animals were submitted to minimal stress ante mortem conditions. Pig behaviour was recorded at the experimental farm, raceway to the CO2 stunning system and during the stunning period. Corneal reflexes were recorded after stunning as well. There were no differences in feed intake among diets (p>0.05) during the 5 days of treatment. Thehalothane positive (nn) group had lower intake than the halothane negative (NN) group(p<0.01). The behaviour of the pigs in the raceway did not differ (p>0.05) among treatments or halothane genotype. A significant (p<0.001) interaction diet*halothane was found in the time to appear the first retreat attempt during the exposure to the CO2 system. In the nn group, the time of performing the first retreat attempt was later in the Mg (p<0.05) than the Control group. Moreover, in the Mg group, the nn had a later (p<0.05) first retreat attempt than the NN. Thus, Mg supplementation could have a positive effect on welfare of nn pigs. The nn had a lower proportion of animals thatshowed corneal reflexes after stunning than NN, indicating a higher effectiveness of thestunning method in nn pigs. Neither Mg nor Trp affected carcass quality and meat quality parameters, although significant differences were found between genotypes

Effect of diet composition and ration size on key enzyme activities of glycolysis-gluconeogenesis, pentose phosphate pathway and amino acid metabolism in liver of Sparus aurata

The effects of diet composition and ration size on the activities of key enzymes involved in intermediary metabolism were studied in the liver of gilthead sea bream (Sparus aurata). Highcarbohydrate, low-protein diets stimulated 6-phosphofructo 1-kinase (EC 2.7.1.11), pyruvate kinase (EC 2.7.1.40), glucose-6-phosphate dehydrogenase (EC 1.1.1.49) and 6-phosphogluconate dehydrogenase (EC 1.1.1.44) enzyme activities, while they decreased alanine aminotransferase (EC 2.6.1.2) activity. A high degree of correlation was found between food ration size and the activity of the enzymes 6-phosphofructo 1-kinase, pyruvate kinase, glucose-6-phosphate dehydrogenase (positive correlations) and fructose-1,6-bisphosphatase (EC 3.1.3.11) (negative correlation). These correlations matched well with the high correlation also found between ration size and growth rate in starved fish refed for 22 d. Limited feeding (5 g/kg body weight) for 22 d decreased the activities of the key enzymes for glycolysis and lipogenesis, and alanine aminotransferase activity. The findings presented here indicate a high level of metabolic adaptation to both diet type and ration size. In particular, adaptation of enzyme activities to the consumption of a diet with a high carbohydrate level suggests that a carnivorous fish like Sparus aurata can tolerate partial replacement of protein by carbohydrate in the commercial diets supplied in culture. The relationship between enzyme activities, ration size and fish growth indicates that the enzymes quickly respond to dietary manipulations of cultured fish.

Effect of diet composition and ration size on key enzyme activities of glycolysis-gluconeogenesis, pentose phosphate pathway and amino acid metabolism in liver of Sparus aurata

The effects of diet composition and ration size on the activities of key enzymes involved in intermediary metabolism were studied in the liver of gilthead sea bream (Sparus aurata). Highcarbohydrate, low-protein diets stimulated 6-phosphofructo 1-kinase (EC 2.7.1.11), pyruvate kinase (EC 2.7.1.40), glucose-6-phosphate dehydrogenase (EC 1.1.1.49) and 6-phosphogluconate dehydrogenase (EC 1.1.1.44) enzyme activities, while they decreased alanine aminotransferase (EC 2.6.1.2) activity. A high degree of correlation was found between food ration size and the activity of the enzymes 6-phosphofructo 1-kinase, pyruvate kinase, glucose-6-phosphate dehydrogenase (positive correlations) and fructose-1,6-bisphosphatase (EC 3.1.3.11) (negative correlation). These correlations matched well with the high correlation also found between ration size and growth rate in starved fish refed for 22 d. Limited feeding (5 g/kg body weight) for 22 d decreased the activities of the key enzymes for glycolysis and lipogenesis, and alanine aminotransferase activity. The findings presented here indicate a high level of metabolic adaptation to both diet type and ration size. In particular, adaptation of enzyme activities to the consumption of a diet with a high carbohydrate level suggests that a carnivorous fish like Sparus aurata can tolerate partial replacement of protein by carbohydrate in the commercial diets supplied in culture. The relationship between enzyme activities, ration size and fish growth indicates that the enzymes quickly respond to dietary manipulations of cultured fish.

Cyclin-dependent kinases 4 and 6 control tumor progression and direct glucose oxidation in the pentose cycle

Cyclin-dependent kinases CDK4 and CDK6 are essential for the control of the cell cycle through the G1 phase. Aberrant expression of CDK4 and CDK6 is a hall- mark of cancer, which would suggest that CDK4 and CDK6 are attractive targets for cancer therapy. Herein, we report that calcein AM is a potent specific inhibitor of CDK4 and CDK6 in HCT116 human colon adenocarcinoma cells, inhibiting retinoblastoma protein (pRb) phosphorylation and inducing cell cycle arrest in the G1 phase. The metabolic effects of calcein AM (the calcein acetoxymethyl-ester) on HCT116 cells were also evaluated and the flux between the oxidative and non-oxidative branches of the pentose phos-phate pathway was significantly altered. To elucidate whe-ther these metabolic changes were due to the inhibition of CDK4 and CDK6, we also characterized the metabolic profile of a CDK4, CDK6 and CDK2 triple knockout of mouse embryonic fibroblasts. The results show that the metabolic profile associated with the depletion of CDK4, CDK6 and CDK2 coincides with the metabolic changes induced by calcein AM on HCT116 cells, thus confirming that the inhibition of CDK4 and CDK6 disrupts the balance between the oxidative and non-oxidative branches of the pentose phosphate pathway. Taken together, these results indicate that low doses of calcein can halt cell division and kill tumor cells. Thus, selective inhibition of CDK4 and CDK6 may be of greater pharmacological interest, since inhibitors of these kinases affect both cell cycle progression and the robust metabolic profile of tumors.

Anivellament de coneixements en el trànsit batxillerat/universitat: anàlisi dels continguts en microcòpia al grau de Farmàcia

Durante el curso 2010-2011, en la asignatura Iniciació al Treball de Laboratori (ITL) del grado de Farmacia, se recopilaron datos de encuestas incluídas en las libretas de laboratorio de los alumnos, para comparar el nivel de conocimientos previos adquiridos durante el Bachillerato sobre el contenido de la práctica “Microscopía y estereomicroscopía ópticas” con el nivel de esta unidad de enseñanza universitaria. Se procesaron datos de 200 estudiantes. A partir de las respuestas se ha definido un total de 20 ítems: 19 desglosan los contenidos adquiridos en la sesión (no adquiridos previamente en Bachillerato) y 1 es para los estudiantes con todos los contenidos adquiridos antes de ingresar en la UB.

Mitochondrial fatty acid oxidation in obesity

Significance: Current lifestyles with high-energy diets and little exercise are triggering an alarming growth in obesity. Excess of adiposity is leading to severe increases in associated pathologies, such as insulin resistance, type 2 diabetes, atherosclerosis, cancer, arthritis, asthma, and hypertension. This, together with the lack of efficient obesity drugs, is the driving force behind much research. Recent Advances: Traditional anti-obesity strategies focused on reducing food intake and increasing physical activity. However, recent results suggest that enhancing cellular energy expenditure may be an attractive alternative therapy. Critical Issues: This review evaluates recent discoveries regarding mitochondrial fatty acid oxidation (FAO) and its potential as a therapy for obesity. We focus on the still controversial beneficial effects of increased FAO in liver and muscle, recent studies on how to potentiate adipose tissue energy expenditure, and the different hypotheses involving FAO and the reactive oxygen species production in the hypothalamic control of food intake. Future Directions: The present review aims to provide an overview of novel anti-obesity strategies that target mitochondrial FAO and that will definitively be of high interest in the future research to fight against obesity-related disorders.

Efeito do triacilglicerídeo de cadeia média, da fibra e do cálcio na disponibilidade de magnésio e de zinco pelo método in vitro e metodologia de superfície de resposta

Nutritional therapy with enteral diets became highly specialized in the last years. This work aims to study the effect of the components of a formulation, namely fiber, calcium and medium-chain triglycerides, for dialysability of minerals. Analysis of multiple variables was done using response surface methodology. The level curve showed that the tertiary interaction MCT-fiber-calcium was the one that presented the highest synergism in the formulation. The proportion of 33% MCT, 25% fiber and 42% calcium, gave the best formulation for availability of magnesium.

Altered nitrogen balance and decreased urea excretion in male rats fed cafeteria diet are related to arginine availability

Hyperlipidic diets limit glucose oxidation and favor amino acid preservation, hampering the elimination of excess dietary nitrogen and the catabolic utilization of amino acids.We analyzed whether reduced urea excretion was a consequence of higherNO ; (nitrite,nitrate, and other derivatives) availability caused by increased nitric oxide production in metabolic syndrome. Rats fed a cafeteria diet for 30 days had a higher intake and accumulation of amino acid nitrogen and lower urea excretion.There were no differences in plasma nitrate or nitrite. NO and creatinine excretion accounted for only a small part of total nitrogen excretion. Rats fed a cafeteria diet had higher plasma levels of glutamine, serine, threonine, glycine, and ornithinewhen comparedwith controls,whereas arginine was lower. Liver carbamoyl-phosphate synthetase I activity was higher in cafeteria diet-fed rats, but arginase I was lower. The high carbamoyl-phosphate synthetase activity and ornithine levels suggest activation of the urea cycle in cafeteria diet-fed rats, but low arginine levels point to a block in the urea cycle between ornithine and arginine, thereby preventing the elimination of excess nitrogen as urea. The ultimate consequence of this paradoxical block in the urea cycle seems to be the limitation of arginine production and/or availability.

Efeito antagônico do ferro e do zinco em uma formulação de alimentação enteral utilizando planejamento de misturas da metodologia de superfície de resposta

Nutritional therapy with enteral diets became substantially specialized over the last years. This work's aim was to study the effect of the components of a formulation: fiber, calcium and medium-chain triglycerides for dialysability of minerals. Analysis of multiple variables was carried out using response surface methodology. The level curve showed an antagonic effect of interaction between iron and zinc. TCM was the variable responsible for characterizing competition between the two minerals in the formulation. More studies on foods are needed for knowing the effecs of minerals in formulations.

Determinação de fósforo biodisponível em rações de peixes utilizando extração assistida por ultra-som e espectrofotometria no visível

The aim of the present work was to develop and optimize a method for determination of bioavailable phosphorus in samples of feces and fish feed using ultrasound extraction and subsequent quantification by visible spectrophotometry. Using as extractor solution HNO3 0.50 mol L-1, the great conditions of extraction established were: sample mass - 100 mg, samples granulometry - < 60 µm, sonification time - five cycles of 40 s and ultrasound potency - 136 W. The proposed method was applied in studies of digestibility of this nutrient in different feeds used in diets of juvenile of Nile tilapia.

The Influence of Diet and Microbes on Colonic Immune Regulation and their Implications on Type 1 Diabetes

Dietary and microbial factors are thought to contribute to the rapidly increasing prevalence of T1D in many countries worldwide. The impact of these factors on immune regulation and diabetes development in non-obese diabetic (NOD) mice are investigated in this thesis. Diabetes can be prevented in NOD mice through dietary manipulation. Diet affects the composition of intestinal microbiota, which may subsequently influence intestinal immune homeostasis. However, the specific effects of anti-diabetogenic diets on gut immunity and the explicit associations between intestinal immune disruption and type 1 diabetes onset remain unclear. The research presented herein demonstrates that newly weaned NOD mice suffer from a mild level of colitis, which shifts the colonic immune cell balance towards a proinflammatory status. Several aberrations can also be observed in the peritoneal B cells of NOD mice; an increase in activation marker expression, increased trafficking to the pancreatic lymph nodes and significantly higher antigen presenting cell (APC) efficiency towards insulin-specific T cells. A shift towards inflammation is likewise observed in the colon of germ-free NOD mice, but signs of peritoneal B cell activation are lacking in these mice. Remarkably, most of the abnormalities in the colon, peritoneal macrophages and the peritoneal B cell APC activity of NOD mice are abrogated when NOD mice are maintained on a diabetes-preventive, soy-based diet (ProSobee) from the time of weaning. Dietary and microbial factors hence have a significant impact on colonic immune regulation and peritoneal B cell activation and it is suggested that these factors influence diabetes development in NOD mice.

Viestintä ravitsemusosaamisen kehittämisessä Case:Sairaalan ateriaprosessi

Tutkielman tarkoituksena oli tutkia viestinnän merkitystä osaamisen kehittämisessä. Tavoitteena oli tutkia, miten viestintä edistää ravitsemusosaamisen kehittämistä sairaalan ateriaprosessissa. Tutkimuksessa etsittiin vastausta kysymyksiin, mitkä ovat ravitsemusosaamisen kehittämisen ja viestinnän tavoitteet, millä työyhteisöviestinnän foorumeilla uuden ravitsemushoitosuosituksen ja ravitsemushoidon strategian edellyttämiä muutoksia käsitellään ja millaisia työssä oppimisen prosesseja näillä foorumeilla on tunnistettavissa. Empirian näkökulmasta tutkimusta voidaan kuvata tapaustutkimukseksi. Tapauksena on sairaalan ateriaprosessi. Tutkimuksen valmistelevana aineistona käytettiin uutta ravitsemushoitosuositusta (Nuutinen ym. 2010), jota täydennettiin haastatteluaineistolla. Tutkimuksessa ovat edustettuina hoitotyön, ruokapalvelun ja ravitsemushoidon asiantuntemuksen näkökulmat sairaalasta sekä ammatti- ja aikuisopistosta. Tutkimusmenetelmänä käytettiin teemahaastatteluja. Haastattelut nauhoitettiin ja litteroitiin tekstimuotoon. Aineisto analysoitiin teemakortiston ja teemoittelun avulla. Tutkimuksen tulokset osoittavat, että ravitsemusosaamisen kehittämisen tavoitteena on uuden ravitsemushoitosuosituksen ja ravitsemushoidon strategian edellyttämien muutosten toteuttaminen sairaalan ravitsemushoidon prosesseissa ja tuotteissa. Ravitsemusosaamisen kehittämisen tavoitteena on tässä yhteydessä ateriaprosessin ja ruokapalvelun tuotteiden eli ruokavalioiden kehittäminen. Ravitsemushoidon kehittämisen tarkoituksena on asiakkaiden toipumisen, elämänlaadun ja hyvinvoinnin edistäminen sekä terveydenhuollon kustannusten säästäminen. Viestinnällä on tärkeä merkitys ravitsemusosaamisen kehittämisessä. Viestinnän avulla edistetään yksilöllistä ja yhteistä eli tiimioppimista vuorovaikutuksen kautta. Ruokapalvelu- ja hoitohenkilöstön sekä ravitsemushoidon asiantuntijoiden välinen vuoropuhelu nähdään tärkeänä ravitsemusosaamisen kehittämisessä. Vuoropuhelun avulla vahvistetaan ravitsemushoitoon liittyvää tietopohjaa ja yhteistä käsitteistöä. Tavoitteena on yhteisen kielen ja toimintamallin luominen ravitsemushoidon kehittämiseen. Ravitsemushoitosuosituksen ja ravitsemushoidon strategian edellyttämiä muutoksia käsitellään ulkoisissa ja sisäisissä verkostoissa esimerkiksi ravitsemus-yhdyshenkilöverkoston tapaamisissa, moniammatillisissa työryhmissä, henkilöstö- ja oppisopimuskoulutuksissa sekä työfoorumilla eli fyysisessä työtilassa ja hyödyntäen viestintäteknologiaa. Hoitotyön, ruokapalvelun ja ravitsemushoidon asiantuntijoilla/opettajilla on tärkeä rooli ravitsemusosaamisen kehittämiseen liittyvässä työssä oppimisen ohjaamisessa. Ravitsemusosaamisen kehittämisessä on tunnistettavissa sosiaalisia, reflektiivisiä, kognitiivisia ja operationaalisia työssä oppimisen prosesseja. Sosiaalisia prosesseja ovat työkokemusten vaihdanta ja reflektiivisiä niiden arviointi. Kognitiivisten prosessien tarkoitus on tiedonhankinta ja prosessointi, jolloin yhdistetään kokemustietoa sekä uutta ravitsemustieteellistä tietoa. Tavoitteena on yhteisen kielen ja toimintamallin luominen, jota kokeillaan käytännössä. Operationaalisia prosesseja ovat fyysisessä työtilassa tapahtuva kokeilemalla, tekemällä ja soveltamalla oppiminen, jolloin uutta toimintamallia esimerkiksi vajaaravitsemuksen seulontaa, ateriatilausta tai reseptiikkaa kokeillaan käytännössä. Johtopäätöksenä voidaan todeta, että sairaalassa on omaksuttu oppivan organisaation periaatteita ravitsemusosaamisen kehittämisessä. Ravitsemusosaamisen kehittäminen on yhteydessä muutokseen, strategiaan, prosessien ja tuotteiden kehittämiseen. Viestinnän avulla edistetään ravitsemushoitosuosituksen ja ravitsemushoidon strategian edellyttämien muutosten toteuttamista sairaalan ateriaprosessissa ja ruokavalioissa. Hoito- ja ruokapalveluhenkilöstön sekä ravitsemushoidon asiantuntijoiden välisen vuoropuhelun tavoitteena on yhteisen kielen ja toimintamallin luominen ravitsemushoidon kehittämiseen. Tutkimus palvelee ravitsemusosaamisen kehittämistä sairaalan ateriaprosessissa. Tutkimuksen tuloksia on mahdollista käyttää vertailuoppimismateriaalina terveydenhuollon organisaatioissa ja verkostoissa.