Transcobalamin C776G genotype modifies the association between vitamin B12 and homocysteine in older Hispanics.

Background/objectivesA common polymorphism, C776G, in the plasma B12 transport protein transcobalamin (TC), encodes for either proline or arginine at codon 259. This polymorphism may affect the affinity of TC for B12 and subsequent delivery of B12 to tissues.Subjects/methodsTC genotype and its associations with indicators of B12 status, including total B12, holotranscobalamin (holoTC), methylmalonic acid and homocysteine, were evaluated in a cohort of elderly Latinos (N=554, age 60-93 years) from the Sacramento Area Latino Study on Aging (SALSA).ResultsThe distribution of TC genotypes was 41.3% homozygous reference (776CC) and 11.6% homozygous variant (776GG). No differences between the homozygous genotypes were observed in total B12, holoTC, methylmalonic acid or homocysteine. The holoTC/total B12 ratio was lower in the 776GG group compared with the 776CC group (P=0.04). Significant interactions of TC genotype with total B12 (P=0.04) and with holoTC (P< or =0.03) were observed such that mean homocysteine concentrations and the odds ratios for hyperhomocysteinemia (>13 micromol/l) were higher in the 776CC subjects compared with all carriers of the G allele (776CG and 776GG combined) when total B12 (<156 pmol/l) or holoTC (<35 pmol/l) were low.ConclusionsThis population of older Latinos has a lower prevalence of the TC 776GG variant than reported for Caucasian populations. The association between vitamin B12 and homocysteine concentrations is modified by TC 776 genotype. It remains to be determined whether the TC C776G polymorphism has a significant effect on the hematological and neurological manifestations of B12 deficiency or on vascular and other morbidities associated with hyperhomocysteinemia

Muscle size explains low passive skeletal muscle force in heart failure patients.

BACKGROUND: Alterations in skeletal muscle function and architecture have been linked to the compromised exercise capacity characterizing chronic heart failure (CHF). However, how passive skeletal muscle force is affected in CHF is not clear. Understanding passive force characteristics in CHF can help further elucidate the extent to which altered contractile properties and/or architecture might affect muscle and locomotor function. Therefore, the aim of this study was to investigate passive force in a single muscle for which non-invasive measures of muscle size and estimates of fiber force are possible, the soleus (SOL), both in CHF patients and age- and physical activity-matched control participants. METHODS: Passive SOL muscle force and size were obtained by means of a novel approach combining experimental data (dynamometry, electromyography, ultrasound imaging) with a musculoskeletal model. RESULTS: We found reduced passive SOL forces (∼30%) (at the same relative levels of muscle stretch) in CHF vs. healthy individuals. This difference was eliminated when force was normalized by physiological cross sectional area, indicating that reduced force output may be most strongly associated with muscle size. Nevertheless, passive force was significantly higher in CHF at a given absolute muscle length (non length-normalized) and likely explained by the shorter muscle slack lengths and optimal muscle lengths measured in CHF compared to the control participants. This later factor may lead to altered performance of the SOL in functional tasks such gait. DISCUSSION: These findings suggest introducing exercise rehabilitation targeting muscle hypertrophy and, specifically for the calf muscles, exercise that promotes muscle lengthening

Impact of handgrip exercise intensity on brachial artery flow-mediated dilation.

PURPOSE: Previous studies that have examined the impact of exercise intensity on conduit artery endothelial function have involved large muscle group exercise which induces local and systemic effects. The aim of this study was to examine flow-mediated dilation (FMD) before and after incremental intensities of handgrip exercise (HE), to assess the role of local factors such as blood flow and shear rate on post-exercise brachial artery function. METHODS: Eleven healthy men attended the laboratory on three occasions. Subjects undertook 30 min of handgrip exercise at three intensities (5, 10 or 15 % MVC). Brachial artery FMD, shear and blood flow patterns were examined before, immediately after and 60 min post exercise. RESULTS: Handgrip exercise increased mean and antegrade shear rate (SR) and blood flow (BF) and reduced retrograde SR and BF (all P < 0.01). Exercise intensity was associated with a dose-dependent increase in both mean and antegrade BF and SR (interaction, P < 0.01). Post-hoc tests revealed that, whilst handgrip exercise did not immediately induce post-exercise changes, FMD was significantly higher 60 min post-exercise following the highest exercise intensity (5.9 ± 2.8-10.4 ± 5.8 %, P = 0.01). CONCLUSIONS: Handgrip exercise leads to intensity-and time-dependent changes in conduit artery function, possibly mediated by local increases in shear, with improvement in function evident at 1 h post-exercise when performed at a higher intensity

Brachial and Cerebrovascular Functions Are Enhanced in Postmenopausal Women after Ingestion of Chocolate with a High Concentration of Cocoa.

Background: Cocoa contains polyphenols that are thought to be beneficial for vascular health.Objective: We assessed the impact of chocolate containing distinct concentrations of cocoa on cerebrovascular function and cognition.Methods: Using a counterbalanced within-subject design, we compared the acute impact of consumption of energy-matched chocolate containing 80%, 35%, and 0% single-origin cacao on vascular endothelial function, cognition, and cerebrovascular function in 12 healthy postmenopausal women (mean ± SD age: 57.3 ± 5.3 y). Participants attended a familiarization session, followed by 3 experimental trials, each separated by 1 wk. Outcome measures included cerebral blood flow velocity (CBFv) responses, recorded before and during completion of a computerized cognitive assessment battery (CogState); brachial artery flow-mediated dilation (FMD); and hemodynamic responses (heart rate and blood pressure).Results: When CBFv data before and after chocolate intake were compared between conditions through the use of 2-factor ANOVA, an interaction effect (P = 0.003) and main effects for chocolate (P = 0.043) and time (P = 0.001) were evident. Post hoc analysis revealed that both milk chocolate (MC; 35% cocoa; P = 0.02) and dark chocolate (DC; 80% cocoa; P = 0.003) induced significantly lower cerebral blood flow responses during the cognitive tasks, after normalizing for changes in arterial pressure. DC consumption also increased brachial FMD compared with the baseline value before chocolate consumption (P = 0.002), whereas MC and white chocolate (0% cocoa) caused no change (P-interaction between conditions = 0.034).Conclusions: Consumption of chocolate containing high concentrations of cocoa enhanced vascular endothelial function, which was reflected by improvements in FMD. Cognitive function outcomes did not differ between conditions; however, cerebral blood flow responses during these cognitive tasks were lower in those consuming MC and DC. These findings suggest that chocolate containing high concentrations of cocoa may modify the relation between cerebral metabolism and blood flow responses in postmenopausal women. This trial was registered at www.ANZCTR.orgau as ACTRN12616000990426

Impact of commonly prescribed exercise interventions on platelet activation in physically inactive and overweight men.

The exercise paradox infers that, despite the well-established cardioprotective effects of repeated episodic exercise (training), the risk of acute atherothrombotic events may be transiently increased during and soon after an exercise bout. However, the acute impact of different exercise modalities on platelet function has not previously been addressed. We hypothesized that distinct modalities of exercise would have differing effects on in vivo platelet activation and reactivity to agonists which induce monocyte-platelet aggregate (MPA) formation. Eight middle-aged (53.5 ± 1.6 years) male participants took part in four 30 min experimental interventions (aerobic AE, resistance RE, combined aerobic/resistance exercise CARE, or no-exercise NE), in random order. Blood samples were collected before, immediately after, and 1 h after each intervention, and incubated with one of three agonists of physiologically/clinically relevant pathways of platelet activation (thrombin receptor activating peptide-6 TRAP, arachidonic acid AA, and cross-linked collagen-related peptide xCRP). In the presence of AA, TRAP, and xCRP, both RE and CARE evoked increases in MPAs immediately post-exercise (P < 0.01), whereas only AA significantly increased MPAs immediately after AE (P < 0.01). These increases in platelet activation post-exercise were transient, as responses approached pre-exercise levels by 1 h. These are the first data to suggest that exercise involving a resistance component in humans may transiently increase platelet-mediated thrombotic risk more than aerobic modalities

Knots and Particles

Using methods of high performance computing, we have found indications that knotlike structures appear as stable finite energy solitons in a realistic 3+1 dimensional model. We have explicitly simulated the unknot and trefoil configurations, and our results suggest that all torus knots appear as solitons. Our observations open new theoretical possibilities in scenarios where stringlike structures appear, including physics of fundamental interactions and early universe cosmology. In nematic liquid crystals and 3He superfluids such knotted solitons might actually be observed.Comment: 9 pages, 4 color eps figures and one b/w because of size limit (color version available from authors

Consumption of dark chocolate attenuates subsequent food intake compared with milk and white chocolate in postmenopausal women.

BACKGROUND: Chocolate has a reputation for contributing to weight gain due to its high fat, sugar and calorie content. However, the effect of varying concentrations of cocoa in chocolate on energy intake and appetite is not clear. OBJECTIVE: To compare the acute effect of consuming an isocaloric dose of dark, milk and white chocolate on subsequent energy intake, appetite and mood in postmenopausal women. METHODS: Fourteen healthy postmenopausal women (57.6 ± 4.8yr) attended an introductory session followed by three experimental trials performed in a counterbalanced order at a standardised time of day, each separated by one week. Ad libitum energy intake, perceived appetite, mood and appetite-related peptides were assessed in response to consumption of 80% cocoa [dark chocolate], 35% cocoa [milk chocolate] and cocoa butter [white chocolate] (2099 kJ), prepared from a single-origin cacao bean. RESULTS: Ad libitum energy intake was significantly lower following dark (1355 ± 750 kJ) compared with both milk (1693 ± 969 kJ; P = 0.008) and white (1842 ± 756 kJ; P = 0.001) chocolate consumption. Blood glucose and insulin concentrations were transiently elevated in response to white and milk chocolate consumption compared with the dark chocolate (P  0.05). CONCLUSIONS: Dark chocolate attenuates subsequent food intake in postmenopausal women, compared to the impact of milk and white chocolate consumption