Prostaglandin E(2) increases cyclic AMP and inhibits endothelin-1 production/secretion by guinea-pig tracheal epithelial cells through EP(4) receptors

Prostaglandin E(2) (PGE(2)) increased adenosine 3' : 5'-cyclic monophosphate (cyclic AMP) formation in tracheal epithelial cells and concomitantly decreased the production/secretion of immunoreactive endothelin (irET). Naturally occurring prostanoids and selective and non-selective EP receptor agonists showed the following rank order of potency in stimulating cyclic AMP generation by epithelial cells: PGE(2) (EP-selective)>16,16-dimethyl PGE(2) (EP-selective)>11-deoxy PGE(2) (EP-selective)>iloprost (IP/EP(1)/EP(3)-selective), butaprost (EP(2)-selective), PGD(2) (DP-selective), PGF(2alpha) (FP-selective). The lack of responsiveness of the latter prostanoids indicated that the prostanoid receptor present in these cells is not of the DP, FP, IP, EP(1), EP(2) or EP(3) subtype. Pre-incubating the cells with the selective TP/EP(4)-receptor antagonists AH23848B and AH22921X antagonized the PGE(2)-evoked cyclic AMP generation. This suggested that EP(4) receptors mediate PGE(2) effects. However, in addition to any antagonistic effects at EP(4)-receptors, both compounds, to a different extent, modified cyclic AMP metabolism. The selective EP(1), DP and EP(2) receptor antagonist (AH6809) failed to inhibit PGE(2)-evoked cyclic AMP generation which confirmed that the EP(2) receptor subtype did not contribute to the change in cyclic AMP formation in these cells. The PGE(2)-induced inhibition of irET production by guinea-pig tracheal epithelial cells was due to cyclic AMP generation and activation of the cyclic AMP-dependent protein kinase since this effect was reverted by the cyclic AMP antagonist Rp-cAMPS. These results provide the first evidence supporting the existence of a functional prostaglandin E(2) receptor that shares the pharmacological features of the EP(4)-receptor subtype in guinea-pig tracheal epithelial cells. These receptors modulate cyclic AMP formation as well as ET-1 production/secretion in these cells.     

Corrosion Resistance of 3D Printed Ti6Al4V Gyroid Lattices with Varying Porosity

Corrosion of medical implants is a possible failure mode via induced local inflammatory effects, systemic deposition and corrosion related mechanical failure. Cyclic potentiodynamic polarisation (CPP) testing was utilized to evaluate the effect of increased porosity (60% and 80%) and decreased wall thickness in gyroid lattice structures on the electrochemical behaviour of LPBF Ti6Al4V structures. The use of CPP allowed for the landmarks of breakdown potential, resting potential and vertex potential to be analysed, as well as facilitating the construction of Tafel plots and qualitative Goldberg analysis. The results indicated that 60% gyroid samples were most susceptible to the onset of pitting corrosion when compared to 80% gyroid and solid samples. This was shown through decreased breakdown and vertex potentials and were found to correlate to increased lattice surface area to void volume ratio. Tafel plots indicated that despite the earlier onset of pitting corrosion, both gyroid test groups displayed lower rates of corrosion per year, indicating a lower severity of corrosion. This study highlighted inherent tradeoffs between lattice optimisation and corrosion behaviour with a potential parabolic link between void volume, surface area and corrosion being identified. This potential link is supported by 60% gyroid samples having the lowest breakdown potentials, but investigation into other porosity ranges is suggested to support the hypothesis. All 3D printed materials studied here showed breakdown potentials higher than ASTM F2129′s suggestion of 800 mV for evaluation within the physiological environment, indicating that under static conditions pitting and crevice corrosion should not initiate within the body.     

From Efficacy Research to Large-Scale Impact on Undernutrition: The Role of Organizational Cultures

Undernutrition in low-income countries is receiving unprecedented attention at global and national levels due to the convergence of many forces, including strong evidence concerning its magnitude, consequences, and potential solutions and effective advocacy by many organizations. The translation of this attention into large-scale reductions in undernutrition at the country level requires the alignment and support of many organizations in the development and implementation of a coherent policy agenda for nutrition, including the strengthening of operational and strategic capacities and a supportive research agenda. However, many countries experience difficulties achieving such alignment. This article uses the concept of organizational culture to better understand some of the reasons for these difficulties. This concept is applied to the constellation of organizations that make up the “National Nutrition Network” in a given country and some of the individual organizations within that network, including academic institutions that conduct research on undernutrition. We illustrate this concept through a case study involving a middle-income country. We conclude that efforts to align organizations in support of coherent nutrition agendas should do the following: 1) make intentional and sustained efforts to foster common understanding, shared learning, and socialization of new members and other elements of a shared culture among partners; 2) seek a way to frame problems and solutions in a fashion that enables individual organizations to secure some of their particular interests by joining the effort; and 3) not only advocate on the importance of nutrition but also insist that high-level officials hold organizations accountable for aligning in support of common-interest solutions (through some elements of a common culture) that can be effective and appropriate in the national context. We further conclude that a culture change is needed within academic departments if the discipline of nutrition is to play a central role in translating the findings from efficacy trials into large-scale reductions in undernutrition.     

Effects of a 3‐month supplementation with a novel soluble highly viscous polysaccharide on anthropometry and blood lipids in nondieting overweight or obese adults

Background: High viscosity fibre is known to exert many beneficial effects on appetite and metabolism. It could potentially help in weight management, in dieting or nondieting individuals. The present study investigated the effects of the daily intake of a novel high viscosity polysaccharide (HVP) over 3 months in nondieting obese or overweight men and women. Methods: The study comprised a double‐blind, randomised controlled clinical trial. Participants ingested 5–15 g per day of either HVP (n = 29, experimental group) or inulin (n = 30, control group) for 15 weeks. Changes in anthropometry (weight, waist and hip circumferences), blood lipids and glucose tolerance were studied from the beginning to the end of administration. Compliance and tolerance were examined. Results: Differences appeared between HVP and inulin supplementation in female participants only. Mean (SD) decreases in body weight [1.6 (3.2) kg; approximately 2% of initial weight] and hip circumference [2.8 (3.6 ) cm] occurred in women of the HVP group but not in controls (Time × Group interactions, P ≤ 0.002). Total, high‐density lipoprotein and low‐density lipoprotein‐cholesterol were lower at the end of supplementation in the women of the HVP group compared to controls (P ≤ 0.021). No effect appeared in waist circumference and triacylglycerol. No difference was noted in the number or severity of the adverse effects reported in both groups. Adverse effects were mild and agreed with commonly reported reactions to intake of dietary fibre. Conclusions: Beneficial although modest effects appeared after several weeks of daily HVP intake in nondieting obese or overweight women. The effects of HVP should be investigated in the context of a weight loss programme.