Eating well with Canada's Food Guide (2007): development of the food intake pattern

A food intake pattern specifying amounts and types of food was created for Canada's revised food guide, Eating Well with Canada's Food Guide (2007), using a two-step modeling process. In step one, food composites were manipulated to develop a food intake pattern. The second step used the step one food intake pattern to create 500 simulated diets for each of 16 age and gender groups. The resulting nutrient content distributions were evaluated relative to Dietary Reference Intake reference values. The modeling cycled between these two steps until a satisfactory pattern was achieved. The final pattern reflects modeling, a review of associations between foods and chronic disease, and input received during consultation.     

The influence of trait and induced state impulsivity on food intake in normal-weight healthy women

Previous research has linked overeating and overweight/obesity to impulsivity. To find out whether impulsivity causes overeating and hence overweight and obesity, we attempted to prime the concept of impulsivity in healthy participants. In a within-subjects design one sample participated in two conditions. In both conditions participants did a priming task that either hinted subtly at the concept of impulsivity or that was neutral in content. Each time the priming task was followed by a bogus taste test. Trait impulsivity was measured by means of a behavioural task and self-report. Firstly, we hypothesized that participants would eat more during the taste test after they had been primed with the concept "impulsivity" compared to after the control session. Secondly, we expected that a more impulsive personality would predict a heightened food intake. Thirdly, we expected that impulsivity would predict food intake better than restraint. The results showed that both the self-report measure of impulsivity and the behavioural task predicted food intake. Restraint did not significantly predict food intake. Primed impulsivity did not increase food intake, possibly because the priming effect did not last long enough.     

High consumptions of grain, fish, dairy products and combinations of these are associated with a low prevalence of metabolic syndrome

OBJECTIVE: To analyse the relation between various food groups and the frequency of insulin resistance syndrome (IRS). DESIGN: A sample of 912 men aged 45-64 years was randomly selected. Questionnaires on risk factors and a three consecutive day food diary were completed. Height, weight, waist circumference, and blood pressure were measured. A fasting blood sample was analysed for lipid and glucose measurements. The NCEP-ATP-III definition was used to assess IRS. Data were analysed according to quintiles of food groups and medians of dairy products, fish, or cereal grains. RESULTS: The prevalence of IRS was 23.5%. It reached 29.0%, 28.1% and 28.1% when the intake was below the median for fish, dairy products, and grain, respectively. When consumptions of all three types of food were higher than the median, the prevalence reached 13.1%, and when they were lower, the prevalence was 37.9% (p<0.001). In logistic regression adjusted for confounders (centre, age, physical activities, education level, smoking, dieting, alcohol intake, treatments for hypertension and dyslipidaemia, energy intake, and diet quality index) the odds ratios for IRS (above median value v below) were 0.51 (95% confidence interval, 0.36 to 0.71) for fish, 0.67 (0.47 to 0.94) for dairy products, and 0.69 (0.47 to 1.01) for grain. When intakes of all three kinds of food were high, the OR was 0.22 (0.10 to 0.44). CONCLUSIONS: A high consumption of dairy products, fish, or cereal grains is associated with a lower probability of IRS. The probability decreases when intakes of all three types of food were high.     

Brief O2 uploading during continuous hypothermic machine perfusion is simple yet effective oxygenation method to improve initial kidney function in a porcine autotransplant model

With oxygenation proposed as a resuscitative measure during hypothermic models of preservation, the aim of this study was to evaluate the optimal start time of oxygenation during continuous hypothermic machine perfusion (HMP). In this porcine ischemia‐reperfusion autotransplant model, the left kidney of a ±40 kg pig was exposed to 30 minutes of warm ischemia prior to 22 hours of HMP and autotransplantation. Kidneys were randomized to receive 2 hours of oxygenation during HMP either at the start (n = 6), or end of the perfusion (n = 5) and outcomes were compared to standard, nonoxygenated HMP (n = 6) and continuous oxygenated HMP (n = 8). The brief initial and continuous oxygenated HMP groups were associated with superior graft recovery compared to either standard, nonoxygenated HMP or kidneys oxygenated at the end of HMP. This correlated with significant metabolic differences in perfusate (eg, lactate, succinate, flavin mononucleotide) and tissues (eg, succinate, adenosine triphosphate, hypoxia‐inducible factor‐1α, nuclear factor erythroid 2‐related factor 2) suggesting superior mitochondrial preservation with initial oxygenation. Brief initial O₂ uploading during HMP at procurement site might be an easy and effective preservation strategy to maintain aerobic metabolism, protect mitochondria, and achieve an improved early renal graft function compared with standard HMP or oxygen supply shortly at the end of HMP preservation.     

Mapping the cerebral monoamine oxidase type A: positron emission tomography characterization of the reversible selective inhibitor [11C]befloxatone

Befloxatone is a competitive and reversible inhibitor of monoamine oxidase-A (MAOI-A). The aim of the study was to characterize the in vivo properties of [(11)C]befloxatone and to validate its use as a ligand for the study of MAO-A by positron emission tomography (PET). PET studies were performed in baboons after i.v. injection of [(11)C]befloxatone (551 +/- 70 MBq, i.e.14.9 +/- 1.9 mCi). [(11)C]Befloxatone enters rapidly in the brain with a maximum uptake at 30 min. Brain concentration of the tracer is high in thalamus, striatum, pons and cortical structures (1.5-1.8% of injected dose per 100 ml of tissue), and lower in cerebellum (1.07% injected dose/100 ml). Nonsaturable uptake, obtained after a pretreatment with a high dose of nonlabeled befloxatone (0.4 mg/kg), is very low and represents only 3% of the total uptake. Brain uptake of [(11)C]befloxatone is not altered by a pretreatment of a high dose with lazabemide (0.5 mg/kg i.v.), a selective MAOI-B but is completely blocked by a pretreatment with moclobemide (MAOI-A; 10 mg/kg). This confirms, in vivo, the selectivity of befloxatone for type A MAO. [(11)C]Befloxatone brain radioactivity was displaced by administration of unlabeled befloxatone (30 min after the tracer injection). The displacement of the tracer from its binding sites is dose-dependent, with an ID(50) of 0.02 mg/kg for all studied structures. These results indicate that [(11)C]befloxatone will be an excellent probe for the study of MAO-A in humans using PET.     

The endocytic catalysts,Rab5a and Rab7, are tandem regulators of thyroid hormone production

Rab proteins are small GTPases that control distinct vesicular transport steps. Along the endocytic pathway, Rab5a is a rate-limiting catalyst of internalization, and Rab7 controls trafficking through late endosomes to lysosomes. The dependence of thyroid hormone production by thyrocytes on thyroglobulin endocytosis and intracellular processing in late endosomes/lysosomes suggests that its rate can be regulated by the expression or function of these endocytic catalysts. We compared the expression level and membrane recruitment of Rab5a and Rab7 in autonomous thyroid adenomas (where the cAMP cascade is constitutively activated) and surrounding quiescent tissues. The concentrations of Rab5a and Rab7, but not of Rab8, were coordinately increased up to 6-fold in adenomas, and correlated with a proportionate decrease in soluble thyroglobulin content (reflecting colloid depletion by accelerated endocytic uptake in hyperactive tissue). In adenomas, a higher proportion of Rab5a and Rab7 was membrane associated, and the equilibrium density of particulate Rab7 and iodine shifted toward lysosomal fractions, indicating that progression along the degradation pathway also was promoted. In cultures of polarized human thyrocytes from normal patients, thyroid-stimulating hormone or forskolin increased, to a similar extent, Rab5a and Rab7 but not Rab8 expression, apical endocytosis of thyroglobulin and lucifer yellow, and basolateral secretion of T(3) and T(4). Taken together, these in vivo and in vitro observations demonstrate that thyroid-stimulating hormone, via cAMP, coordinately enhances the expression of Rab5a and Rab7, which promote Tg endocytosis and transfer to lysosomes, respectively, resulting in accelerated thyroid hormone production.     

Caveolin-1 expression is critical for vascular endothelial growth factor-induced ischemic hindlimb collateralization and nitric oxide-mediated angiogenesis

Nitric oxide (NO) is a powerful angiogenic mediator acting downstream of vascular endothelial growth factor (VEGF). Both the endothelial NO synthase (eNOS) and the VEGFR-2 receptor colocalize in caveolae. Because the structural protein of these signaling platforms, caveolin, also represses eNOS activity, changes in its abundance are likely to influence the angiogenic process in various ways. In this study, we used mice deficient for the caveolin-1 gene (Cav-/-) to examine the impact of caveolae suppression in a model of adaptive angiogenesis obtained after femoral artery resection. Evaluation of the ischemic tissue perfusion and histochemical analyses revealed that contrary to Cav+/+ mice, Cav-/- mice failed to recover a functional vasculature and actually lost part of the ligated limbs, thereby recapitulating the effects of the NOS inhibitor L-NAME administered to operated Cav+/+ mice. We also isolated endothelial cells (ECs) from Cav-/- aorta and showed that on VEGF stimulation, NO production and endothelial tube formation were dramatically abrogated when compared with Cav+/+ ECs. The Ser1177 eNOS phosphorylation and Thr495 dephosphorylation but also the ERK phosphorylation were similarly altered in VEGF-treated Cav-/- ECs. Interestingly, caveolin transfection in Cav-/- ECs redirected the VEGFR-2 in caveolar membranes and restored the VEGF-induced ERK and eNOS activation. However, when high levels of recombinant caveolin were reached, VEGF exposure failed to activate ERK and eNOS. These results emphasize the critical role of caveolae in ensuring the coupling between VEGFR-2 stimulation and downstream mediators of angiogenesis. This study also provides new insights to understand the paradoxical roles of caveolin (eg, repressing basal enzyme activity but facilitating activation on agonist stimulation) in cardiovascular pathophysiology.     

Efficient in vitro megakaryocyte maturation using cytokine cocktails optimized by statistical experimental design

OBJECTIVE: A multi-step statistical strategy was applied to quantify individual and interactive effects of cytokines on megakaryopoiesis and to determine the concentration of the selected cytokines that optimize ex vivo megakaryocyte (MK) expansion, maturation, and platelet production in stromal- and serum-free conditions. MATERIALS AND METHODS: Immature MK were first generated from human CD34(+)-enriched cord blood cells cultured for 7 days in conditions favoring MK commitment. Then, the effect of different combinations of cytokines at various concentrations on MK differentiation and platelet production was tested on the day-7 MK. RESULTS: A large-scale screening of 13 cytokines in the presence of thrombopoietin (TPO) using Placket-Burman designs (PBD) was initially performed to identify stimulators of MK maturation. Afterwards, a statistical analysis of the two-level factorial designs revealed that in the presence of TPO, MK maturation was significantly stimulated by stem cell factor (SCF), interleukin (IL)-6, and IL-9, whereas Flt-3 ligand (FL) had a positive effect only on the expansion of MK progenitors. In contrast, erythropoietin (EPO) and IL-8 were inhibitors of MK maturation. A response surface methodology was then used to optimize the concentrations of the selected cytokines (TPO, SCF, IL-6, and IL-9) and defined a new cytokine cocktail that maximized MK expansion and maturation. Importantly, the increased MK output was accompanied by a very high MK purity ( approximately 90%). Another optimum was also found at a higher SCF concentration, which further improved MK expansion and maturation, but reduced MK purity. CONCLUSION: These statistical methods provide an efficient tool to analyze complex systems of cytokines and to develop promising ex vivo MK culture systems for clinical applications.