Differential In Vitro Effects of SGLT2 Inhibitors on Mitochondrial Oxidative Phosphorylation,Glucose Uptake and Cell Metabolism

(1) The cardio-reno-metabolic benefits of the SGLT2 inhibitors canagliflozin (cana), dapagliflozin (dapa), ertugliflozin (ertu), and empagliflozin (empa) have been demonstrated, but it remains unclear whether they exert different off-target effects influencing clinical profiles. (2) We aimed to investigate the effects of SGLT2 inhibitors on mitochondrial function, cellular glucose-uptake (GU), and metabolic pathways in human-umbilical-vein endothelial cells (HUVECs). (3) At 100 µM (supra-pharmacological concentration), cana decreased ECAR by 45% and inhibited GU (IC5o: 14 µM). At 100 µM and 10 µM (pharmacological concentration), cana increased the ADP/ATP ratio, whereas dapa and ertu (3, 10 µM, about 10× the pharmacological concentration) showed no effect. Cana (100 µM) decreased the oxygen consumption rate (OCR) by 60%, while dapa decreased it by 7%, and ertu and empa (all 100 µM) had no significant effect. Cana (100 µM) inhibited GLUT1, but did not significantly affect GLUTs’ expression levels. Cana (100 µM) treatment reduced glycolysis, elevated the amino acids supplying the tricarboxylic-acid cycle, and significantly increased purine/pyrimidine-pathway metabolites, in contrast to dapa (3 µM) and ertu (10 µM). (4) The results confirmed cana´s inhibition of mitochondrial activity and GU at supra-pharmacological and pharmacological concentrations, whereas the dapa, ertu, and empa did not show effects even at supra-pharmacological concentrations. At supra-pharmacological concentrations, cana (but not dapa or ertu) affected multiple cellular pathways and inhibited GLUT1.     

Sensitive determination of volatile aliphatic aldehydes in autoxidized fats and oils by gas chromatographic/electron-capture detection of their O-pentafluorobenzyloxime derivatives

 This paper describes a novel method for the sensitive determination of the volatile aliphatic aldehydes formed by autoxidation in fats and oils. In a solution of fats, the aldehydes are derivatized to the O-pentafluorobenzyloximes (PFBOs) without any isolation procedure. From the mixture, the lipids are removed by silica gel column chromatography using pentane/dichloromethane (4+1) as the eluant. The eluate is evaporated to dryness and the PFBOs are extracted from the residue with a small volume of acetonitrile. They are separated by capillary column gas chromatography and are determined with high selectivity and sensitivity by using an electron-capture detector. The determination limit was as low as 0.01 mg/kg for hexanal. Analysis of a series of corn oil samples yielded high recoveries for 14 aldehydes added at the 1 mg/kg level, with low relative standard deviations of between 3 and 17%. Received: 9 May 1997     

Polychlorinated biphenyl residues in food and human milk: determination of co-planar and mono-ortho substituted congeners

An analytical method is described for determining the residues of coplanar as well as mono-ortho substituted PCB congeners both exhibiting toxicological relevance, in foods of animal origin and in human milk. The unsophisticated procedure, convenient for routine analyses, includes the extraction of lipids, clean-up steps using liquid/liquid partition and column chromatography, fractionation of the congeners using HPLC on a special carbon column with an optimal gradient elution, and capillary column gas chromatography with electron capture or mass spectrometric detection. As preliminary results indicate, the low-chlorinated PCB technical products contribute more to the actual contamination of environment and foods than has been estimated so far. Obviously the co-planar congeners are accumulated during the food chain in a portion different from that found for the other congeners.     

Exposure to secondhand smoke in Germany: air contamination due to smoking in German restaurants, bars, and other venues.

This study quantified exposure to secondhand smoke in German restaurants, bars, and entertainment venues by determining the concentration of respirable suspended particles measuring 2.5 microm or less (PM2.5) in indoor air. The measurements were taken using an inconspicuous device placed on the investigator's table in the venue. The concentration of particulate matter in the indoor air was measured for a minimum of 30 min. A total of 39 restaurants, 20 coffee bars, 12 bars, 9 discothèques, and 20 restaurant cars in trains were visited throughout Germany from September 30 to October 31, 2005. The readings disclosed a median PM2.5 of 260 microg/m3 and an arithmetic mean PM2.5 of 333 microg/m3. Median values were 378 microg/m3 in bars, 131 microg/m3 in cafes, and 173 microg/m3 in restaurants. The highest medians were measured in discothèques and restaurant cars, with values averaging 432 microg/m3 and 525 microg/m3 PM2.5, respectively. This study was the first to show the magnitude and extent of exposure to secondhand smoke on such an extensive scale in Germany. The contaminated air due to smoking is a human carcinogenic and major health hazard, which would be prevented most effectively and completely by implementing a ban on smoking. This study is important for the ongoing national debate in Germany as well as for debates in all countries without smoke-free air legislation, which includes most countries around the world.     

Effect of repeated episodes of generic clinical mastitis on milk yield in dairy cows

Our objective was to estimate the milk losses associated with multiple occurrences of generic bovine clinical mastitis (CM) within and across lactations. We studied 10,380 lactations from 5 large, high-producing dairy herds that used automatic recording of daily milk yields. Mixed models, with a random herd effect and an autoregressive covariance structure to account for repeated measurements, were used to quantify the effect of CM and other control variables (parity, week of lactation, other diseases) on milk yield. Many cows that developed CM were higher producers than their non-mastitic herdmates before CM occurred. Milk yield began to drop after diagnosis; the greatest loss occurred in the first weeks (up to 126 kg) and then gradually tapered to a constant value approximately 2 mo after CM. Mastitic cows often never recovered their potential yield. First-lactation cows lost 164 kg of milk for the first episode and 198 kg for the second in the 2 mo after CM diagnosis, compared with their potential yield. Among older cows, this estimate was 253 kg for the first, 238 kg for the second, and 216 kg for the third CM case. A cow that had 1 or more CM episodes in her previous lactation produced 1.2 kg/d less milk over the whole current lactation (95% confidence interval: 0.6, 1.7) than a cow without CM in her previous lactation. These findings provide dairy producers with information on the average milk loss associated with CM cases without considering the causative agent, and can be used for economic analysis.     

An investigation of the diffraction of waves by complementary infinite double-sectors

Contents In this paper we treat the diffraction by infinite double-sectors. The scalar boundary value problem as well as the electromagnetic boundary value problem is solved using the problem adapted sphero-conal coordinate system. We determine appropriate eigenfunctions and we find a remarkable relation between the eigenvalues of complementary double-sectors due to Babinet's principle. Additionally we consider the diffraction of a plane wave normally incident upon the double-sector for the scalar and for the electromagnetic case.

---

Eine Untersuchung der Beugung von Wellen an komplementären unendlich ausgedehnten Doppelsektoren

Übersicht In dieset Arbeit wird die Beugung an unendlich ausgedehnten Doppelsektoren untersucht. Sowohl das skalare wie auch das elektromagneticsche Randwert-problem werden in elliptischen Kegelkoordinaten als problemangepaßtem Koordinatensystem gelöst. Es werden geeignete Eigenfunktionen bestimmt, wobei sich für die Eigenwerte für zueinander komplementäre Doppelsektoren eine Symmetriebeziehung ergibt, welche dem Babinetschen Prinzip entspricht. Desweiteren wird die Beugung einer senkrecht einfallenden ebenen Welle am Doppelsektor für den skalaren wie auch für den elektromagnetischen Fall untersucht.

     

Demand Side Management for Thermally Activated Building Systems Based on Multiple Linear Regression

The building sector and its heating and cooling represent one of the major consumer of energy worldwide. Simultaneously, the share of fluctuating generation of renewable energies in the energy mix increases. Therefore storage and demand side management technologies are required. The new adaptive and predictive control algorithm for thermally activated building systems (TABS) based on multiple linear regression (AMLR) presented in this paper enables the application of demand side management (DSM) strategies. Based on simulations, different strategies have been compared with each other. By applying the AMLR algorithm, electricity energy cost savings of 38% could be achieved compared to the conventional control strategy for TABS, while increasing the thermal comfort. At the same time, thermal energy demand can be reduced in the range between 4% to 8%, and pump operation time from 86% to 89%.     

Toward efficient Cu(In,Ga)Se2 solar cells prepared by reactive magnetron co‐sputtering from metallic targets in an Ar:H2Se atmosphere

In this paper, we show that a reactive co‐sputtering process using metallic CuGa and In targets; an Ar:H₂Se atmosphere is well suited for the deposition of photoactive Cu(In,Ga)Se₂ (CIGSe) absorber layers for thin‐film solar cells in a single process step. The achievement of single‐phase and well‐crystallized layers is thereby no major problem if a sufficiently high H₂Se content and substrate temperatures in the range of 400–500 °C are used. However, in order to achieve the desired Cu‐poor film stoichiometry, which is crucial for the device performance, it has to be considered already that, at moderate substrate temperatures in the range of 400–500 °C, indium has a strong tendency to re‐evaporate from the film surface if the film composition is Cu‐poor. If excess indium is supplied, this effect can lead to a self‐adjustment of the film composition. This allows a very wide process window in a one‐stage process concerning the supply ratio from the two targets of [Cu]/([In] + [Ga])_supply ≈ 0.35–0.8. However, the maximum efficiencies achievable with such a process are limited to 11.7% because an adequate Cu‐poor composition can only be achieved with significant Cu‐poor conditions, which allow only a low material quality. By using an improved process with an intermediate Cu‐rich composition and a final Cu‐poor stage, the absorber quality could be significantly improved; efficiencies of up to 14.3% have been achieved with CIGSe films prepared on Na‐doped Mo back contacts. Copyright © 2015 John Wiley & Sons, Ltd.