Serial Changes in Norepinephrine Kinetics Associated With Feeding Dogs a High-Fat Diet

J Clin Hypertens (Greenwich). 2010;12:117–124. © 2009 Wiley Periodicals, Inc. The role of increased sympathetic nervous system (SNS) activity in the pathogenesis of obesity hypertension and insulin resistance is controversial. Eight dogs were instrumented and fed a high-fat diet (HFD) for 6 weeks. Dogs were evaluated for changes in weight, blood pressure, insulin resistance, and norepinephrine (NE) kinetics using a two-compartment model. The HFD resulted in weight gain, hypertension, and insulin resistance. During the 6 weeks of the HFD, although plasma NE concentration trended toward increasing ( P =.09), SNS, assessed by NE kinetic studies, significantly increased ( P =.009). Within 1 week of starting the HFD, NE release into the extravascular compartment (NE 2 ) increased from 3.44±0.59 μg/mL to 4.87±0.80 μg/mL ( P <.01) and this increase was maintained over the next 5 weeks of the HFD (NE 2 at week 6 was 4.66±0.97 μg/mL). In addition to the increased NE 2 there was also a significant increase in NE clearance ( P =.04). There were significant correlations between the increase in NE 2 and both the development of insulin resistance and hypertension. This study supports the hypothesis that activation of the SNS plays a pivotal role in the metabolic and hemodynamic changes that occur with weight gain induced by HFD.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78633/1/j.1751-7176.2009.00230.x.pd

In vivo platelet aggregation and plasma catecholamines in acute myocardial infarction

In vivo platelet aggregation assessed with the Filtragometer and potential correlates were compared among (1) patients with acute myocardial infarction (AMI), (2) normal controls, (3) patients with acute chest pain in whom AMI was eventually ruled out (ROMI), and (4) chronic outpatients (Cardiac Clinic group) with a history of myocardial infarction and/or angina pectoris. The measure was independent of sex, age, platelet count, immediate food intake, serum cholesterol, and triglyceride levels. The AMI group showed higher in vivo platelet aggregation than any of the other three groups (p &lt; 0.01). Least in vivo aggregation was seen in the normal group. Despite lack of correlation with the platelet aggregation measure, plasma epinephrine and norepinephrine showed statistically significant differences between the AMI and each of the other three groups. Our data support an association between platelet function and AMI, although not necessarily a cause and effect relationship.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/23797/1/0000035.pd

What’s Worth Talking About? Information Theory Reveals How Children Balance Informativeness and Ease of Production

Of all the things we could say, what determines what is worth saying? Greenfield’s principle of informativeness states that, right from the onset of language, humans selectively comment on whatever they find unexpected. We quantify this tendency using information theoretic measures, and test the counterintuitive prediction that children will produce words that are low frequency given the context because these will be most informative. Using corpora of child directed speech, we identified adjectives that varied in how informative (i.e., unexpected) they were given the noun they modified. Three-year-olds (N=31, replication N=13) heard an experimenter use these adjectives to describe pictures. The children’s task was then to describe the pictures to another person. As the information content of the experimenter’s adjective increased, so did children’s tendency to comment on the feature that adjective had encoded. Furthermore, our analyses suggest that children balance this informativeness with a competing drive to ease production

Effect of an oral [alpha]2-adrenergic blocker (MK-912) on pancreatic islet function in non-insulin-dependent diabetes mellitus

We used MK-912, a potent new selective [alpha]2-adrenergic receptor antagonist that is active orally, to study the effect of short-term, selective [alpha]2-blockade on fasting plasma glucose (FPG) and pancreatic islet function in non-insulin-dependent diabetes (NIDDM). Ten asymptomatic patients with NIDDM received either a single oral dose of MK-912 (2 mg) or placebo in a double-blind, cross-over study. B-cell function was measured by the acute insulin response (AIR) to glucose (1.66 mmol/kg intravenously [IV]) and by the AIR to arginine (5 g IV) during a hyperglycemic glucose clamp at a mean glucose level of 32.1 mmol/L to provide an estimation of maximal B-cell secretory capacity. A-cell function was estimated by the acute glucagon response (AGR) to arginine during the glucose clamp. Effective [alpha]2-adrenergic blockade was apparently achieved, as there were substantial increases of plasma norepinephrine (NE) (P P P P P P P P = .06) and the C-peptide response (P = .07) to glucose compared with placebo. There was a small, but significant, overall treatment effect for both the AIR and AGR to arginine with MK-912 (both P 2-adrenergic blockade; (2) a small decrease of FPG and a small increase of fasting plasma insulin; (3) a small improvement of B-cell function due to an increase in maximal B-cell secretory capacity; and (4) a small increase in basal and stimulated glucagon. These findings suggest that endogenous [alpha]2-adrenergic tone may contribute, although to a small extent, to the impaired B-cell function in NIDDM. If an [alpha]2-blocker becomes available that does not increase BP, studies would be warranted to evaluate its potential impact on glucose regulation in patients with NIDDM.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29070/1/0000105.pd

Circadian fluctuation of plasma epinephrine in supine humans

Previous studies have demonstrated circadian fluctuations of systemic catecholamines in man. However, methodological differences and conflicting results with epinephrine are apparent. In the present study, plasma and urinary epinephrine and norepinephrine and plasma cortisol were studied in healthy young adult males over 24 hr with 20 min plasma sampling and EEG monitoring of sleep. Plasma epinephrine did not have a circadian variation in supine subjects. Urinary epinephrine levels and small urinary circadian variations were increased by normal posture and activity. Sleep and sleep stage were not associated with different plasma epinephrine levels, and no ultradian fluctuation was observed. Levels of norepinephrine and cortisol were normal. Based on all studies to date, it appears that basal plasma epinephrine has either a very small amplitude or no circadian rhythm, but that changes in posture and activity or the rest/activity cycle may modify this pattern.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26858/1/0000423.pd

best practices in bioassay development to support registration of biopharmaceuticals

Biological activity is a critical quality attribute for biopharmaceuticals, which is accurately measured using an appropriate relative potency bioassay. Developing a bioassay is a complex, rigorous undertaking that needs to address several challenges including modelling all of the mechanisms of action associated with the biotherapeutic. Bioassay development is also an exciting and fast evolving field, not only from a scientific, medical and technological point of view, but also in terms of statistical approaches and regulatory expectations. This has led to an industry-wide discussion on the most appropriate ways to develop, validate and control the bioassays throughout the drug lifecycle

The discovery of the faintest known Milky Way satellite using UNIONS

We present the discovery of Ursa Major III/UNIONS 1, the least luminous known satellite of the Milky Way, which is estimated to have an absolute V-band magnitude of $+2.2^{+0.4}_{-0.3}$ mag, equivalent to a total stellar mass of 16$^{+6}_{-5}$ M$_{\odot}$. Ursa Major III/UNIONS 1 was uncovered in the deep, wide-field Ultraviolet Near Infrared Optical Northern Survey (UNIONS) and is consistent with an old ($\tau > 11$ Gyr), metal-poor ([Fe/H] $\sim -2.2$) stellar population at a heliocentric distance of $\sim$ 10 kpc. Despite being compact ($r_{\text{h}} = 3\pm1$ pc) and composed of so few stars, we confirm the reality of Ursa Major III/UNIONS 1 with Keck II/DEIMOS follow-up spectroscopy and identify 11 radial velocity members, 8 of which have full astrometric data from $Gaia$ and are co-moving based on their proper motions. Based on these 11 radial velocity members, we derive an intrinsic velocity dispersion of $3.7^{+1.4}_{-1.0}$ km s$^{-1}$ but some caveats preclude this value from being interpreted as a direct indicator of the underlying gravitational potential at this time. Primarily, the exclusion of the largest velocity outlier from the member list drops the velocity dispersion to $1.9^{+1.4}_{-1.1}$ km s$^{-1}$, and the subsequent removal of an additional outlier star produces an unresolved velocity dispersion. While the presence of binary stars may be inflating the measurement, the possibility of a significant velocity dispersion makes Ursa Major III/UNIONS 1 a high priority candidate for multi-epoch spectroscopic follow-ups to deduce to true nature of this incredibly faint satellite.Comment: 21 pages, 9 figures, 3 tables; Accepted for publication in Ap

Addressing health literacy in patient decision aids

BackgroundEffective use of a patient decision aid (PtDA) can be affected by the user’s health literacy and the PtDA’s characteristics. Systematic reviews of the relevant literature can guide PtDA developers to attend to the health literacy needs of patients. The reviews reported here aimed to assess:1. a) the effects of health literacy / numeracy on selected decision-making outcomes, and b) the effects of interventions designed to mitigate the influence of lower health literacy on decision-making outcomes, and2. the extent to which existing PtDAs a) account for health literacy, and b) are tested in lower health literacy populations.MethodsWe reviewed literature for evidence relevant to these two aims. When high-quality systematic reviews existed, we summarized their evidence. When reviews were unavailable, we conducted our own systematic reviews.ResultsAim 1: In an existing systematic review of PtDA trials, lower health literacy was associated with lower patient health knowledge (14 of 16 eligible studies). Fourteen studies reported practical design strategies to improve knowledge for lower health literacy patients. In our own systematic review, no studies reported on values clarity per se, but in 2 lower health literacy was related to higher decisional uncertainty and regret. Lower health literacy was associated with less desire for involvement in 3 studies, less question-asking in 2, and less patient-centered communication in 4 studies; its effects on other measures of patient involvement were mixed. Only one study assessed the effects of a health literacy intervention on outcomes; it showed that using video to improve the salience of health states reduced decisional uncertainty. Aim 2: In our review of 97 trials, only 3 PtDAs overtly addressed the needs of lower health literacy users. In 90% of trials, user health literacy and readability of the PtDA were not reported. However, increases in knowledge and informed choice were reported in those studies in which health literacy needs were addressed.ConclusionLower health literacy affects key decision-making outcomes, but few existing PtDAs have addressed the needs of lower health literacy users. The specific effects of PtDAs designed to mitigate the influence of low health literacy are unknown. More attention to the needs of patients with lower health literacy is indicated, to ensure that PtDAs are appropriate for lower as well as higher health literacy patients

Selection of diazotrophic bacterial communities in biological sand filter mesocosms used for the treatment of phenolic-laden wastewater

Agri effluents such as winery or olive mill waste-waters are characterized by high phenolic concentrations. These compounds are highly toxic and generally refractory to biodegradation. Biological sand filters (BSFs) represent inexpensive, environmentally friendly, and sustainable wastewater treatment systems which rely vastly on microbial catabolic processes. Using denaturing gradient gel electrophoresis and terminal-restriction fragment length polymorphism, this study aimed to assess the impact of increasing concentrations of synthetic phenolic-rich wastewater, ranging from 96 mg L−1 gallic acid and138 mg L−1 vanillin (i.e., a total chemical oxygen demand (COD) of 234 mg L−1) to 2,400mg L−1 gallic acid and 3,442 mg L−1 vanillin (5,842 mg COD L−1), on bacterialcommunities and the specific functional diazotrophic community from BSF mesocosms. This amendment procedure instigated efficient BSF phenolic removal, significant modifications of the bacterial communities, and notably led to the selection of a phenolic-resistant and less diverse diazotrophic community. This suggests that bioavailable N is crucial in the functioning of biological treatment processes involving microbial communities, and thus that functional alterations in the bacterial communities in BSFs ensure provision of sufficient bioavailable nitrogen for the degradation of wastewater with a high C/N ratio.Web of Scienc