Effect of glucose on endothelin-1-induced calcium transients in cultured bovine retinal pericytes

Published work has shown that endothelin-l-induced contractility of bovine retinal pericytes is reduced after culture in high concentrations of glucose. The purpose of the present study was to establish the profile of endothelin-l-induced calcium transients in pericytes and to identify changes occurring after culture in high concentrations of glucose. Glucose had no effect on basal levels of cytosolic calcium or on endothelin-l-induced calcium release from intracellular stores. However, influx of calcium from the extracellular medium after endothelin-l stimulation was reduced in pericytes that had been cultured in 25 mM D-glucose. L-type Ca2+ currents were identified by patch clamping. The L-type Ca2+ channel agonist, (-)-Bay K8644, caused less influx of calcium from the extracellular medium in pericytes that had been cultured in 25 mM D-glucose than in those cultured with 5 mM D-glucose. However, 3-O-methylglucose, a nonmetabolizable analogue of glucose which can cause glycation, had similar effects to those of high concentrations of glucose. The results suggest that reduced function of the L-type Ca2+ channel that occurs in bovine retinal pericytes after culture in high concentrations of D-glucose is probably due to glycation of a channel protein.

The effect of hypoxia on propranolol clearance during antegrade and retrograde flow in the isolated perfused rat liver preparation

We investigated, using the single-pass isolated perfused rat liver preparation, whether the centrilobular location of hepatic oxidative drug metabolism could be a contributing factor to the marked sensitivity of drug oxidation to hypoxia. Livers (N = 7) were each perfused for 130 min with 2 micrograms/mL (+)-propranolol, a drug metabolized almost entirely by oxidation in the rat. The direction of flow was reversed after 60 min, the order of flow direction being randomized. Normal oxygenation was used during the first 30 min of antegrade and of retrograde perfusion, but in the second 30 min perfusate was equilibrated with a N2/O2 mixture designed to reduce hepatic oxygen delivery by half. During normal oxygenation there was no significant difference between antegrade and retrograde perfusion in hepatic oxygen delivery and physiological parameters such as oxygen consumption and extraction, perfusion pressure and bile flow. During hypoxia, mean oxygen delivery was slightly lower with retrograde perfusion (retrograde: mean = 2.37 mumol/min/g liver, range = 1.56-3.17; antegrade: mean = 2.90 mumol/min/g liver, range = 1.96-4.08; P = 0.04), but there was no significant difference in physiological parameters within each liver (P > 0.05). Propranolol clearance during normal oxygenation was similar to the perfusion rate (10 mL/min) and was the same for both directions of perfusion (antegrade 9.88 +/- 0.07 mL/min, retrograde 9.88 +/- 0.13 mL/min, P > 0.05). Hypoxia reduced propranolol clearance substantially, but the decrease was significantly greater with antegrade perfusion (5.65 +/- 1.89 mL/min) than with retrograde perfusion (6.76 +/- 1.95 mL/min, P = 0.014). Oxidative drug metabolism is located primarily in the centrilobular zone and sinusoidal oxygen concentration is lowest in the "downstream" zone with both antegrade and retrograde perfusion. These findings suggest that the centrilobular location of propranolol metabolism may influence the effect of hypoxia on propranolol elimination, but is not a major contributor to the marked sensitivity of propranolol elimination to hypoxia antegrade perfusion.

Smart meter devices and the effect of feedback on residential electricity consumption: Evidence from a natural experiment in Northern Ireland

Using a unique set of data and exploiting a large-scale natural experiment, we estimate the effect of real-time usage information on residential electricity consumption in Northern Ireland. Starting in April 2002, the utility replaced prepayment meters with advanced meters that allow the consumer to track usage in real-time. We rely on this event, account for the endogeneity of price and payment plan with consumption through a plan selection correction term, and find that the provision of information is associated with a decline in electricity consumption of 11-17%. We find that the reduction is robust to different specifications, selection-bias correction methods and subsamples of the original data. The advanced metering program delivers reasonably cost-effective reductions in carbon dioxide emissions, even under the most conservative usage reduction scenarios.

Effect of precursor on the performance of alumina for the dehydration of methanol to dimethyl ether

Dimethyl ether (DME) is amongst one of the most promising alternative, renewable and clean fuels being considered as a future energy carrier. In this study, the comparative catalytic performance of γ-Al2O3 prepared from two common precursors (aluminum nitrate (AN) and aluminum chloride (AC)) is presented. The impact of calcination temperature was evaluated in order to optimize both the precursor and pre-treatment conditions for the production of DME from methanol in a fixed bed reactor. The catalysts were characterized by TGA, XRD, BET and TPD-pyridine. Under reaction conditions where the temperature ranged from 180 °C to 300 °C with a WHSV = 12.1 h−1 it was found that all the catalysts prepared from AN(η-Al2O3) showed higher activity, at all calcination temperatures, than those prepared from AC(γ-Al2O3). In this study the optimum catalyst was produced from AN and calcined at 550 °C. This catalyst showed a high degree of stability and had double the activity of the commercial γ-Al2O3 or 87% of the activity of commercial ZSM-5(80) at 250 °C.

Carbon flow in an upland grassland: effect of liming on the flux of recently photosynthesized carbon to rhizosphere soil

The effect of liming on the flow of recently photosynthesized carbon to rhizosphere soil was studied using (CO2)-C-13 pulse labelling, in an upland grassland ecosystem in Scotland. The use of C-13 enabled detection, in the field, of the effect of a 4-year liming period of selected soil plots on C allocation from plant biomass to soil, in comparison with unlimed plots. Photosynthetic rates and carbon turnover were higher in plants grown in limed soils than in those from unlimed plots. Higher delta(13)C% values were detected in shoots from limed plants than in those from unlimed plants in samples clipped within 15 days of the end of pulse labelling. Analysis of the aboveground plant production corresponding to the 4-year period of liming indicated that the standing biomass was higher in plots that received lime. Lower delta(13)C% values in limed roots compared with unlimed roots were found, whereas no significant difference was detected between soil samples. Extrapolation of our results indicated that more C has been lost through the soil than has been gained via photosynthetic assimilation because of pasture liming in Scotland during the period 1990-1998. However, the uncertainty associated with such extrapolation based on this single study is high and these estimates are provided only to set our findings in the broader context of national soil carbon emissions.

Effect of microstructure on the fatigue properties of Ti-6Al-4V titanium alloys

Through an analysis on microstructure and high cycle fatigue (HCF) properties of Ti-6Al-4V alloys which were selected from literature, the effects of microstructure types and microstructure parameters on HCF properties were investigated systematically. The results show that the HCF properties are strongly determined by microstructure types for Ti-6Al-4V. Generally the HCF strengths of different microstructures decrease in the order of bimodal, lamellar and equiaxed microstructure. Additionally, microstructure parameters such as the primary a (a) content and the a grain size in bimodal microstructures, the a lamellar width in lamellar microstructure and the a grain size in equiaxed microstructures, can influence the HCF properties. © 2012 Elsevier Ltd.

Effect of simvastatin on physiological and biological outcomes in patients undergoing esophagectomy: a randomised placebo controlled trial

OBJECTIVE: To test whether simvastatin improves physiological and biological outcomes in patients undergoing esophagectomy.

BACKGROUND: One-lung ventilation during esophagectomy is associated with inflammation, alveolar epithelial and systemic endothelial injury, and the development of acute lung injury (ALI). Statins that modify many of the underlying processes are a potential therapy to prevent ALI.

METHODS: We conducted a randomized double-blind placebo-controlled trial in patients undergoing esophagectomy. Patients received simvastatin 80 mg or placebo enterally for 4 days preoperatively and 7 days postoperatively. The primary end point was pulmonary dead space (Vd/Vt) at 6 hours after esophagectomy or before extubation. Inflammation was assessed by plasma cytokines and intraoperative exhaled breath condensate pH; alveolar type 1 epithelial injury was assessed by plasma receptor for advanced glycation end products and systemic endothelial injury by the urine albumin-creatinine ratio.

RESULTS: Thirty-nine patients were randomized; 8 patients did not undergo surgery and were excluded. Fifteen patients received simvastatin and 16 received placebo. There was no difference in Vd/Vt or other physiological outcomes. Simvastatin resulted in a significant decrease in plasma MCP-1 on day 3 and reduced exhaled breath condensate acidification. Plasma receptor for advanced glycation end products was significantly lower in the simvastatin-treated group, as was the urine albumin-creatinine ratio on day 7 postsurgery. ALI developed in 4 patients in the placebo group and no patients in the simvastatin group although this difference was not statistically significant (P = 0.1).

CONCLUSIONS: In this proof of concept study, pretreatment with simvastatin in esophagectomy decreased biomarkers of inflammation as well as pulmonary epithelial and systemic endothelial injury.