Enzymatically modified isoquercitrin improves endothelial function in volunteers at risk of cardiovascular disease

A higher intake of food rich in flavonoids such as quercetin can reduce the risk of CVD. Enzymatically modified isoquercitrin (EMIQ®) has a bioavailability 17-fold higher than quercetin aglycone and has shown potential CVD moderating effects in animal studies. The present study aimed to determine whether acute ingestion of EMIQ® improves endothelial function, blood pressure (BP) and cognitive function in human volunteers at risk of CVD. Twenty-five participants (twelve males and thirteen females) with at least one CVD risk factor completed this randomised, controlled, crossover study. In a random order, participants were given EMIQ® (2 mg aglycone equivalent)/kg body weight or placebo alongside a standard breakfast meal. Endothelial function, assessed by flow-mediated dilatation (FMD) of the brachial artery was measured before and 1·5 h after intervention. BP, arterial stiffness, cognitive function, BP during cognitive stress and measures of quercetin metabolites, oxidative stress and markers of nitric oxide (NO) production were assessed post-intervention. After adjustment for pre-treatment measurements and treatment order, EMIQ® treatment resulted in a significantly higher FMD response compared with the placebo (1·80 (95 % CI 0·23, 3·37) %; P = 0·025). Plasma concentrations of quercetin metabolites were significantly higher (P \u3c 0·001) after EMIQ® treatment compared with the placebo. No changes in BP, arterial stiffness, cognitive function or biochemical parameters were observed. In this human intervention study, the acute administration of EMIQ® significantly increased circulating quercetin metabolites and improved endothelial function. Further clinical trials are required to assess whether health benefits are associated with long-term EMIQ® consumption

Flavonoid-Rich Apple Improves Endothelial Function in Individuals at Risk for Cardiovascular Disease: A Randomized Controlled Clinical Trial

Scope The cardioprotective effects of apples are primarily attributed to flavonoids, found predominantly in the skin. This study aimed to determine if acute and/or chronic (4 weeks) ingestion of flavonoid-rich apples improves endothelial function, blood pressure (BP), and arterial stiffness in individuals at risk for cardiovascular diseases (CVD). Methods and results In this randomized, controlled cross-over trial, acute and 4 week intake of apple with skin (high flavonoid apple, HFA) is compared to intake of apple flesh only (low flavonoid apple, LFA) in 30 participants. The primary outcome is endothelial function assessed using flow-mediated dilation (FMD) of the brachial artery, while main secondary outcomes are 24 h ambulatory BP and arterial stiffness. Other outcomes include fasting serum glucose and lipoprotein profile, plasma heme oxygenase-1 (Hmox-1), F2-isoprostanes, flavonoid metabolites, and plasma and salivary nitrate (NO3−) and nitrite (NO2−) concentrations. Compared to LFA control, the HFA results in a significant increase in FMD acutely (0.8%, p \u3c 0.001) and after 4 weeks chronic intake (0.5%, p \u3c 0.001), and in plasma flavonoid metabolites (p \u3c 0.0001). Other outcomes are not altered significantly. Conclusion A lower risk of CVD with higher apple consumption could be mediated by the beneficial effect of apple skin on endothelial function, both acutely and chronically

Impairment of early fracture healing by skeletal muscle trauma is restored by FK506

BACKGROUND: Heightened local inflammation due to muscle trauma or disease is associated with impaired bone regeneration. METHODS: We hypothesized that FK506, an FDA approved immunomodulatory compound with neurotrophic and osteogenic effects, will rescue the early phase of fracture healing which is impaired by concomitant muscle trauma in male (~4 months old) Lewis rats. FK506 (1 mg/kg; i.p.) or saline was administered systemically for 14 days after an endogenously healing tibia osteotomy was created and fixed with an intermedullary pin, and the overlying tibialis anterior (TA) muscle was either left uninjured or incurred volumetric muscle loss injury (6 mm full thickness biopsy from middle third of the muscle). RESULTS: The salient observations of this study were that 1) concomitant TA muscle trauma impaired recovery of tibia mechanical properties 28 days post-injury, 2) FK506 administration rescued the recovery of tibia mechanical properties in the presence of concomitant TA muscle trauma but did not augment mechanical recovery of an isolated osteotomy (no muscle trauma), 3) T lymphocytes and macrophage presence within the traumatized musculature were heightened by trauma and attenuated by FK506 3 days post-injury, and 4) T lymphocyte but not macrophage presence within the fracture callus were attenuated by FK506 at 14 days post-injury. FK506 did not improve TA muscle isometric torque production CONCLUSION: Collectively, these findings support the administration of FK506 to ameliorate healing of fractures with severe muscle trauma comorbidity. The results suggest one potential mechanism of action is a reduction in local T lymphocytes within the injured musculoskeletal tissue, though other mechanisms to include direct osteogenic effects of FK506 require further investigation

The role of molecular testing and enzyme analysis in the management of hypomorphic citrullinemia

No Abstract.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/69185/1/33256_ftp.pd

Gas flows around 2 young stellar clusters in NGC2264

Observations of the dust and gas toward two young stellar clusters, IRS1 and IRS2, in the NGC2264 star forming region are presented. Continuum emission is used to locate the dusty envelopes around the clusters and individual protostars within and line emission from the J=3-2 transitions of HCO+ and H13CO+ is used to diagnose the gas flows around them. The molecular abundance, velocity centroid and dispersion are approximately constant across the IRS1 clump. With these constraints, the self-absorbed HCO+ lines are modeled as a large scale collapse, with speed v_in=0.3 km/s and mass infall rate dM/dt=4e-4 Msun/yr, falling onto an expanding central core. The signature of large scale collapse, with a similar speed and mass infall rate, is also found toward IRS2 but again appears disrupted at small scales. Individual protostars are resolved in this cluster and their size and velocity dispersion show that the stellar system is currently bound and no older than 0.5 Myr, but is destined to become unbound and disperse as the surrounding cloud material is lost.Comment: 13 page, 6 figures (4 color); accepted for publication in the Ap

Dietary nitrate and diet quality: An examination of changing dietary intakes within a representative sample of Australian women

Dietary nitrate is increasingly linked to a variety of beneficial health outcomes. Our purpose was to estimate dietary nitrate consumption and identify key dietary changes which have occurred over time within a representative sample of Australian women. Women from the 1946–1951 cohort of the Australian Longitudinal Study on Women’s Health with complete food frequency questionnaire data for both 2001 and 2013 were included for analysis. Dietary nitrate intakes were calculated using key published nitrate databases. Diet quality scores including the Australian Recommended Food Score, the Mediterranean Diet Score and the Nutrient Rich Foods Index were calculated along with food group serves as per the Australian Dietary Guidelines. Wilcoxon matched pairs tests were used to test for change in dietary intakes and Spearman’s correlations were used to examine associations. In our sample of 8161 Australian women, dietary nitrate intakes were on average 65–70 mg/day, and we detected a significant increase in dietary nitrate consumption over time (+6.57 mg/day). Vegetables were the primary source of dietary nitrate (81–83%), in particular lettuce (26%), spinach (14–20%), beetroot (10–11%), and celery (7–8%) contributed primarily to vegetable nitrate intakes. Further, increased dietary nitrate intakes were associated with improved diet quality scores (r = 0.3, p \u3c 0.0001). Although there is emerging evidence indicating that higher habitual dietary nitrate intakes are associated with reduced morbidity and mortality, future work in this area should consider how dietary nitrate within the context of overall diet quality can facilitate health to ensure consistent public health messages are conveyed

Nitrate-rich vegetables do not lower blood pressure in individuals with mildly elevated blood pressure: A 4-wk randomized controlled crossover trial

Background - Emerging evidence suggests that increasing intakes of nitrate-rich vegetables may be an effective approach to reduce blood pressure. Objective - Our primary aim was to determine whether daily consumption of nitrate-rich vegetables over 4 wk would result in lower blood pressure. Design - Thirty participants with prehypertension or untreated grade 1 hypertension were recruited to a randomized controlled crossover trial with 4-wk treatment periods separated by 4-wk washout periods. Participants completed 3 treatments in random order: 1) increased intake (∼200 g/d) of nitrate-rich vegetables [high-nitrate (HN); ∼150 mg nitrate/d], 2) increased intake (∼200 g/d) of nitrate-poor vegetables [low-nitrate (LN); ∼22 mg nitrate/d], and 3) no increase in vegetables (control; ∼6 mg nitrate/d). Compliance was assessed with the use of food diaries and by measuring plasma nitrate and carotenoids. Nitrate metabolism was assessed with the use of plasma, salivary, and urinary nitrate and nitrite concentrations. The primary outcome was blood pressure assessed by using 24-h ambulatory, home, and clinic measurements. Secondary outcomes included measures of arterial stiffness. Results - Plasma nitrate and nitrite concentrations increased with the HN treatment in comparison to the LN and control treatments (P \u3c 0.001). Plasma carotenoids increased with the HN and LN treatments compared with the control (P \u3c 0.01). HN treatment did not reduce systolic blood pressure [24-h ambulatory—HN: 127.4 ± 1.1 mm Hg; LN: 128.6 ± 1.1 mm Hg; control: 126.2 ± 1.1 mm Hg (P = 0.20); home—HN: 127.4 ± 0.7 mm Hg; LN: 128.7 ± 0.7 mm Hg; control: 128.3 ± 0.7 mm Hg (P = 0.36); clinic—HN: 128.4 ± 1.3 mm Hg; LN: 130.3 ± 1.3 mm Hg; control: 129.8 ± 1.3 mm Hg (P = 0.49)] or diastolic blood pressure compared with LN and control treatments (P \u3e 0.05) after adjustment for pretreatment values, treatment period, and treatment order. Similarly, no differences were observed between treatments for arterial stiffness measures (P \u3e 0.05). Conclusion - Increased intake of nitrate-rich vegetables did not lower blood pressure in prehypertensive or untreated grade 1 hypertensive individuals when compared with increased intake of nitrate-poor vegetables and no increase in vegetables

The effects of vitamin K-rich green leafy vegetables on bone metabolism: a 4-week randomised controlled trial in middle-aged and older individuals

Background: High vegetable intake is associated with beneficial effects on bone. However, the mechanisms remain uncertain. Green leafy vegetables are a rich source of vitamin K1, which is known to have large effects on osteoblasts and osteocalcin (OC) metabolism. Objective: To examine the effects of consumption of two to three extra serves of green leafy vegetables daily on bone metabolism. Methods: Thirty individuals (mean age 61.8 ± 9.9 years, 67% male) completed three experimental phases in a randomised controlled crossover design, each lasting four weeks, with a washout period of four weeks between phases (clinical trial registration: ACTRN12615000194561). The three experimental phases were: (i) increased dietary vitamin K1 by consuming green leafy vegetables (H-K, ~200 g/d containing 164.3 [99.5–384.7] μg/d of vitamin K1), (ii) low vitamin K1 by consuming vitamin K1-poor vegetables (L-K, ~200 g/d containing 9.4 [7.7–11.6] μg/d of vitamin K1), and (iii) control (CON) where participants consumed an energy-matched non-vegetable control. OC forms, total OC (tOC), carboxylated OC (cOC) and undercarboxylated OC (ucOC), were measured in serum pre- and post-intervention for each experimental phase using a sandwich-electrochemiluminescence immunoassay. Results: Pre-intervention tOC, ucOC and ucOC:tOC levels were similar between phases (P \u3e .05). Following H-K, but not L-K, tOC, ucOC and ucOC:tOC levels were significantly lower compared to pre-intervention levels (P ≤ .001) and compared to CON (~14%, 31% and 19%, respectively, all P \u3c .05), while cOC remained unchanged. Conclusions: In middle-aged healthy men and women, an easily achieved increase in dietary intake of vitamin K1-rich green leafy vegetables substantially reduces serum tOC and ucOC suggesting increased entry of OC into bone matrix, where it may improve the material property of bone. In conjunction with previous epidemiological and randomised controlled trial data, these findings suggest that interventions to increase vegetable intake over extended periods should include bone end points including fracture risk

Under pressure: Response urgency modulates striatal and insula activity during decision-making under risk

When deciding whether to bet in situations that involve potential monetary loss or gain (mixed gambles), a subjective sense of pressure can influence the evaluation of the expected utility associated with each choice option. Here, we explored how gambling decisions, their psychophysiological and neural counterparts are modulated by an induced sense of urgency to respond. Urgency influenced decision times and evoked heart rate responses, interacting with the expected value of each gamble. Using functional MRI, we observed that this interaction was associated with changes in the activity of the striatum, a critical region for both reward and choice selection, and within the insula, a region implicated as the substrate of affective feelings arising from interoceptive signals which influence motivational behavior. Our findings bridge current psychophysiological and neurobiological models of value representation and action-programming, identifying the striatum and insular cortex as the key substrates of decision-making under risk and urgency